FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Heatwole, VM Haynes, SR AF Heatwole, VM Haynes, SR TI Association of RB97D, an RRM protein required for male fertility, with a Y chromosome lampbrush loop in Drosophila spermatocytes SO CHROMOSOMA LA English DT Article ID DNA-SEQUENCES; SATELLITE DNA; MELANOGASTER; RNA; HYDEI; ANTIGENS; GENES; SPERMATOGENESIS; HETEROCHROMATIN; ORGANIZATION AB The Y chromosome of Drosophila melanogaster, which is required only for male fertility, contains six loci that are essential for spermatogenesis. In primary spermatocytes, three of these loci form large lampbrush loops containing RNA transcripts and associated proteins. The identities and functions of these Y chromosome loop-binding proteins are largely unknown. This report demonstrates that the RB97D protein, which is essential for spermatogenesis, bound to a specific lampbrush loop. RB97D contains two copies of a well-characterized RNA binding domain, the RNA recognition motif, followed by a proline-glutamine rich domain. Immunohistochemical and immunofluorescence experiments showed that in the testis, RB97D was found only in primary spermatocyte nuclei and associated with the C loop from the ks-1 fertility locus in an RNAse-sensitive manner. The anti-RB97D antibodies also bound a single Y chromosome loop in D. hydei, suggesting that the protein and its loop-binding function have been evolutionarily conserved. These results demonstrate that the proteins that bind lampbrush loops can be essential for fertility. Since RB97D was present only premeiotically, its function is,likely to be directly related to the metabolism of the C loop transcripts. C1 NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. NR 42 TC 24 Z9 24 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD DEC PY 1996 VL 105 IS 5 BP 285 EP 292 DI 10.1007/BF02524646 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WH826 UT WOS:A1996WH82600004 PM 8939821 ER PT J AU Marchetti, F Lowe, X Moore, DH Bishop, J Wyrobek, AJ AF Marchetti, F Lowe, X Moore, DH Bishop, J Wyrobek, AJ TI Paternally inherited chromosomal structural aberrations detected in mouse first-cleavage zygote metaphases by multicolour fluorescence in situ hybridization painting SO CHROMOSOME RESEARCH LA English DT Article DE acrylamide; chromosome painting; germ cell; translocation ID HUMAN PERIPHERAL LYMPHOCYTES; RAY-INDUCED ABERRATIONS; RADIATION IN-VITRO; X-RAY; DNA PROBES; INSITU HYBRIDIZATION; CYTOGENETIC ANALYSIS; REPAIR CAPACITY; GENETIC-DAMAGE; HUMAN-SPERM AB We describe a fluorescence in situ hybridization (FISH) procedure for assessing zygotic risk of paternal exposure to endogenous or exogenous agents. The procedure employs multicolour FISH with chromosome-specific DNA painting probes plus DAPI staining for detecting both balanced and unbalanced chromosomal aberrations in mouse first-cleavage (1-CI) zygote metaphases, Four composite probes specific for chromosomes 1, 2, 3 or X, each labelled with biotin, plus a composite probe specific for chromosome Y labelled with digoxigenin, were used. We applied this method to evaluate the effects of paternal exposure to acrylamide, a model germ cell clastogen. First-cleavage zygote metaphases, collected from untreated females mated to males whose sperm or late spermatids were treated with acrylamide, were scored for the induction of structural aberrations using both chromosome painting (PAINT analysis) and DAPI analysis. Structural chromosomal aberrations were observed in the sperm-derived, but not in the egg-derived, pronuclei. While 59.4% of the zygotes had structural aberrations by DAPI analysis, 94.1% of the same zygotes had structural aberrations by PAINT analysis (P<0.001), illustrating the increased sensitivity for detecting translocations and insertions obtained by adding chromosome painting. These findings show that FISH painting of mouse 1-CI zygotes when used in conjunction with DAPI analysis is a powerful model for investigating the cytogenetic defects transmitted from father to offspring. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Marchetti, F (reprint author), LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,POB 808,LIVERMORE,CA 94550, USA. OI Marchetti, Francesco/0000-0002-9435-4867 FU NIEHS NIH HHS [Y01-ES10203-00] NR 42 TC 19 Z9 19 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD DEC PY 1996 VL 4 IS 8 BP 604 EP 613 DI 10.1007/BF02261723 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WN636 UT WOS:A1996WN63600006 PM 9024977 ER PT J AU Pietinen, P Rimm, EB Korhonen, P Hartman, AM Willett, WC Albanes, D Virtamo, J AF Pietinen, P Rimm, EB Korhonen, P Hartman, AM Willett, WC Albanes, D Virtamo, J TI Intake of dietary fiber and risk of coronary heart disease in a cohort of Finnish men - The alpha-tocopherol, beta-carotene cancer prevention study SO CIRCULATION LA English DT Article DE coronary disease; diet; epidemiology ID ACUTE MYOCARDIAL-INFARCTION; HYPERCHOLESTEROLEMIC MEN; POSTPRANDIAL LIPEMIA; PHYSICAL-ACTIVITY; HEALTHY-ADULTS; OAT BRAN; MORTALITY; WOMEN; HYPERINSULINEMIA; CARBOHYDRATE AB Background Even though dietary fiber has been hypothesized to reduce the risk of coronary heart disease, few large epidemiological studies have examined this relation with good methodology. Methods and Results The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was a randomized, double-blind, placebo-controlled trial with daiIy supplementation of alpha-tocopherol and/or beta-carotene. Of the participants, 21 930 smoking men aged 50 to 69 years who were free of diagnosed cardiovascular disease and had completed a validated dietary questionnaire at baseline were followed for 6.1 years. We monitored the incidence of major coronary events (a combination of first nonfatal myocardial infarction and coronary heart disease death: n=1399) and mortality from coronary heart disease (n=635). Both entities had a significant inverse association with dietary fiber, but the association was stronger for coronary death. For men in the highest quintile of total dietary fiber intake (median, 34.8 g/d), the relative risk for coronary death was 0.69 (95% confidence interval, 0.54 to 0.88; P<.001 for trend) compared with men in the lowest quintile of intake (median, 16.1 g/d). With an adjustment for known cardiovascular risk factors, intake of saturated fatty acids, beta-carotene, vitamin C, and vitamin E did not materially change the result. Water-soluble fiber was slightly more strongly associated with reduced coronary death then water-insoluble fiber, and cereal fiber also had a stronger association than vegetable or fruit fiber. Conclusions These findings suggest that independent of other risk factors, greater intake of foods rich in fiber can substantially reduce the risk, of coronary heart disease, and particularly coronary death, in middle-aged, smoking men. C1 HARVARD UNIV, SCH PUBL HLTH, DEPT NUTR, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD USA. RP NATL PUBL HLTH INST, DEPT NUTR, MANNERHEIMINTIE 166, SF-00300 HELSINKI, FINLAND. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 39 TC 236 Z9 246 U1 1 U2 9 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 DEC 1 PY 1996 VL 94 IS 11 BP 2720 EP 2727 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VV274 UT WOS:A1996VV27400012 PM 8941095 ER PT J AU Becker, LC Pepine, CJ Bonsall, R Cohen, JD Goldberg, AD Coghlan, C Stone, PH Forman, S Knatterud, G Sheps, DS Kaufmann, PG AF Becker, LC Pepine, CJ Bonsall, R Cohen, JD Goldberg, AD Coghlan, C Stone, PH Forman, S Knatterud, G Sheps, DS Kaufmann, PG TI Left ventricular, peripheral vascular, and neurohumoral responses to mental stress in normal middle-aged men and women - Reference group for the psychophysiological investigations of myocardial ischemia (PIMI) study SO CIRCULATION LA English DT Article DE catecholamines; hemodynamics; nervous system, autonomic; nuclear medicine; stress ID CORONARY-ARTERY DISEASE; PLASMA-CATECHOLAMINES; EJECTION FRACTION; CARDIOVASCULAR REACTIVITY; CARDIAC-OUTPUT; BLOOD POOL; EXERCISE; VALIDATION; VOLUME; PROPRANOLOL AB Background The normal cardiovascular response to mental stress in middle-aged and older people has not been well characterized. Methods and Results We studied 29 individuals 45 to 73 years old (15 women, 14 men) who had no coronary risk factors, no history of coronary artery disease, and a negative exercise test. Left ventricular (LV) volumes and global and regional function were assessed by radionuclide ventriculography at rest and during two 5-minute standardized mental stress tasks (simulated public speaking and the Stroop Color-Word Test), administered in random order. A substantial sympathetic response occurred with both mental stress tests, characterized by increases in blood pressure, heart rate, rate-pressure product, cardiac index, and stroke work index and rises in plasma levels of epinephrine and norepinephrine but not beta-endorphin or cortisol. Despite this sympathetic response. LV volume increased and ejection fraction IEF) decreased secondary to an increase in afterload. The change in EF during mental stress varied among individuals but was associated positively with changes in LV contractility and negatively with baseline EF and changes in afterload. EF decreased >5% during mental stress in 12 individuals and >8% in 5; 3 developed regional wall motion abnormalities. Conclusions Menial stress in the laboratory results in a substantial sympathetic response in normal middle-aged and older men and women, but EF commonly falls because of a concomitant rise in afterload. These results provide essential age- and sex-matched reference data for studies of mental stress-induced ischemia in patients with coronary artery disease. C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. UNIV FLORIDA,CARDIOL SECT,GAINESVILLE,FL 32611. EMORY UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ATLANTA,GA. HENRY FORD HOSP,DETROIT,MI 48202. ST LOUIS UNIV,MED CTR,PREVENT CARDIOL PROGRAM,ST LOUIS,MO 63103. UNIV ALABAMA,BEHAV MED UNIT,BIRMINGHAM,AL. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA. UNIV N CAROLINA,DIV CARDIOL,CHAPEL HILL,NC 27515. NHLBI,BEHAV MED BRANCH,BETHESDA,MD. RP Becker, LC (reprint author), MARYLAND MED RES INST,PIMI CLIN COORDINATING CTR,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. FU NHLBI NIH HHS [HV-18114, HV-18119, HV-18120] NR 30 TC 97 Z9 100 U1 1 U2 7 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 1 PY 1996 VL 94 IS 11 BP 2768 EP 2777 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VV274 UT WOS:A1996VV27400018 PM 8941101 ER PT J AU Tsuji, H Larson, MG Venditti, FJ Manders, ES Evans, JC Feldman, CL Levy, D AF Tsuji, H Larson, MG Venditti, FJ Manders, ES Evans, JC Feldman, CL Levy, D TI Impact of reduced heart rate variability on risk for cardiac events - The Framingham Heart Study SO CIRCULATION LA English DT Article DE heart rate; electrocardiography; prognosis; epidemiology ID ACUTE MYOCARDIAL-INFARCTION; FREQUENCY-DOMAIN MEASURES; CORONARY-ARTERY DISEASE; POWER SPECTRAL-ANALYSIS; PERIOD VARIABILITY; HYPERTROPHIC CARDIOMYOPATHY; ELDERLY COHORT; MORTALITY; ASSOCIATION; COMPONENTS AB Background Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a Large community-based population. Methods and Results The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectoris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P=.0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86). Conclusions The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. KANSAI MED UNIV,OSAKA,JAPAN. LAHEY CLIN MED CTR,BURLINGTON,MA 01803. NHLBI,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. BOSTON UNIV,SCH MED,DIV EPIDEMIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DIV PREVENT MED,BOSTON,MA 02118. NR 37 TC 888 Z9 904 U1 8 U2 54 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 1 PY 1996 VL 94 IS 11 BP 2850 EP 2855 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VV274 UT WOS:A1996VV27400029 PM 8941112 ER PT J AU Cape, EG Jones, M Yamada, I VanAuker, MD ValdesCruz, LM AF Cape, EG Jones, M Yamada, I VanAuker, MD ValdesCruz, LM TI Turbulent/viscous interactions control Doppler/catheter pressure discrepancies in aortic stenosis - The role of the Reynolds number SO CIRCULATION LA English DT Article DE blood flow; echocardiography; stenosis; pressure; valves ID DOPPLER ECHOCARDIOGRAPHY; VALVE AREA; GRADIENT; RECOVERY; INVITRO AB Background Despite good correlation between Doppler and catheter pressure drops in numerous reports, it is well known that Doppler tends to apparently overestimate pressure drops obtained by cardiac catheterization. Neither (1) simplification of the Bernoulli equation nor (2) pressure recovery effects can explain this dilemma when taken alone. This study addressed the hypothesis that a Reynolds number-based approach, which characterizes (1) and (2), provides a first step toward better agreement of catheter and Doppler assessments of pressure drops. Methods and Results Doppler and catheter pressure drops. were studied in an in vitro model designed to isolate the proposed Reynolds number effect and in a sheep model with varying degrees of stenosis. Doppler pressure drops in vitro correlated with the directly measured pressure drop for individual Valves (r=.935, .960, .985, .984, .989, and .975) but with markedly different slopes and intercepts. A Bland-Altman type plot showed no useful pattern of discrepancy. The Reynolds number was successful in collapsing the data into the profile proposed in the hypothesis. Parallel results were found in the animal model. Conclusions Apparent overestimation of net pressure drop by Doppler is due to pressure recovery effects, and these effects are countered by both viscous effects and inertial/turbulent effects. Only by reconciliation of discrepancies by use of a quantity such as Reynolds number that embodies the relative importance of competing factors can the noninvasive and invasive methods be connected. This study shows that a Reynolds number-based approach accomplishes this goal both in the idealized in vitro setting and in a biological system. C1 NHLBI,BETHESDA,MD 20892. UNIV COLORADO,CHILDRENS HOSP,HLTH SCI CTR,DIV PEDIAT CARDIOL,DENVER,CO 80218. RP Cape, EG (reprint author), UNIV PITTSBURGH,CHILDRENS HOSP PITTSBURGH,CARDIAC DYNAM LAB,DIV CARDIOL,3705 5TH AVE,PITTSBURGH,PA 15213, USA. NR 13 TC 37 Z9 37 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 1 PY 1996 VL 94 IS 11 BP 2975 EP 2981 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VV274 UT WOS:A1996VV27400046 PM 8941129 ER PT J AU Rossouw, JE AF Rossouw, JE TI Estrogens for prevention of coronary heart disease - Putting the brakes on the bandwagon SO CIRCULATION LA English DT Article DE myocardial infarction; hormones; prevention; women ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; SERUM-CHOLESTEROL; BREAST-CANCER; RISK; PROGESTINS; OSTEOPOROSIS; METAANALYSIS; LIPOPROTEINS; REDUCTION RP Rossouw, JE (reprint author), NATL INST HLTH,OFF DIS PREVENT,WOMENS HLTH INITIAT,FED BLDG,ROOM 6A09,BETHESDA,MD 20892, USA. NR 36 TC 46 Z9 47 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 1 PY 1996 VL 94 IS 11 BP 2982 EP 2985 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VV274 UT WOS:A1996VV27400047 PM 8941130 ER PT J AU Speir, E Shibutani, T Yu, ZX Ferrans, V Epstein, SE AF Speir, E Shibutani, T Yu, ZX Ferrans, V Epstein, SE TI Role of reactive oxygen intermediates in cytomegalovirus gene expression and in the response of human smooth muscle cells to viral infection SO CIRCULATION RESEARCH LA English DT Article DE antioxidant; atherosclerosis; cytomegalovirus; nuclear factor kappa B; reactive oxygen intermediate ID NF-KAPPA-B; HUMAN-IMMUNODEFICIENCY-VIRUS; IMMEDIATE-EARLY PROTEINS; XANTHINE-OXIDASE; PROMOTER-ENHANCER; HYDROGEN-PEROXIDE; ACTIVATION; TRANSCRIPTION; SUPEROXIDE; INDUCTION AB Because cytomegalovirus (CMV) may contribute to restenosis and atherosclerosis and because smooth muscle cells (SMCs) are involved in these disease processes, we examined CMV-SMC interactions. Using confocal microscopy to identify a redox-sensitive fluorescent marker, we found that CMV infection of SMCs generates intracellular reactive oxygen intermediates (ROIs). CMV also activated nuclear factor kappa B (NF kappa B), a cellular transcription factor, as demonstrated by increased NF kappa B binding to DNA (electrophoretic mobility shift assay). Antioxidants inhibited activation, suggesting a role of ROIs in CMV-induced NF kappa B activation. By using antioxidants to assess the role of ROIs in modulating virally mediated effects, we also found that CMV-induced ROIs (1) are critical to the transactivation of the viral major immediate promoter (MIEP) by its immediate-early protein IE72 (determined by cotransfection of an IE72 expression vector and a reporter gene downstream from the MIEP) and (2) are necessary for IE72 expression (determined by immunocytochemistry) and viral replication (determined by viral titer assay on indicator cells) following CMV infection of SMCs. Because ROIs, through activation of NF kappa B, can also induce expression of cellular genes involved in immune and inflammatory responses, the ROI response to CMV infection may also represent a parallel survival mechanism that has evolved in the host cell to protect against viral infection. We conclude that CMV induces intracellular ROI generation within minutes after infection of SMCs and then uses these ROIs to facilitate its own gene expression and replication. Conversely, antioxidants inhibit CMV immediate-early gene expression and viral replication. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,NIH,BETHESDA,MD 20892. NR 47 TC 70 Z9 75 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 DEC PY 1996 VL 79 IS 6 BP 1143 EP 1152 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA VV612 UT WOS:A1996VV61200009 PM 8943952 ER PT J AU Gerszten, RE Luscinskas, FW Ding, HT Dichek, DA Stoolman, LM Gimbrone, MA Rosenzweig, A AF Gerszten, RE Luscinskas, FW Ding, HT Dichek, DA Stoolman, LM Gimbrone, MA Rosenzweig, A TI Adhesion of memory lymphocytes to vascular cell adhesion molecule-1-transduced human vascular endothelial cells under simulated physiological flow conditions in vitro SO CIRCULATION RESEARCH LA English DT Article DE adhesion; endothelium; atherosclerosis; lymphocyte; adenovirus ID INVIVO GENE-TRANSFER; LEUKOCYTE ADHESION; ATHEROSCLEROTIC PLAQUES; RECOMBINANT ADENOVIRUS; MODEL SYSTEM; E-SELECTIN; EXPRESSION; MOLECULE-1; ALPHA; DIVERSITY AB The accumulation of mononuclear leukocytes is an early and persistent finding in atherosclerotic plaques. These mononuclear leukocytes are mostly monocyte-derived, but up to 20% are lymphocytes, predominantly CD4(+) CD45RO(+) (memory) T cells. To evaluate the potential of adenovirus vectors for studies of mononuclear leukocyte recruitment in vitro, we studied the effects of adenovirus vectors per se on human umbilical vein endothelial cells (HUVECs), a well-characterized in vitro model of vascular endothelium. A recombinant adenovirus containing the seven-domain isoform of rabbit vascular cell adhesion molecule-1 (rVCAM-1) was constructed and used to study lymphocyte adhesion under defined laminar flow conditions in transduced HUVEC monolayers. No increase in basal HUVEC surface expression of the inducible endothelial adhesion molecules and markers of activation, E-selectin and VCAM-1, was noted across a broad range of multiplicity of infection. A modest dose-dependent increase in surface intercellular adhesion molecule-1 expression was detectable by flow cytometry at an MOI of >30 plaque-forming units per cell. Under defined laminar how from 1.5 to 0.5 dyne/cm(2), the adenovirus vector carrying r-VCAM-1 mediated stable adhesion of both a Jurkat T-cell line and primary human CD4(+) CD45RO(+) (memory)T cells. Monoclonal antibodies to alpha(4)-integrin or rVCAM-1 abolished adhesion, whereas monoclonal antibodies to CD18 or P-selectin had no effect. We conclude that adenoviral gene transfer is useful for studies of VCAM-1-dependent leukocyte adhesion in vitro and that endothelial expression of VCAM-1 alone, in the absence of overt endothelial cell activation, is sufficient under simulated physiological how conditions to support adhesion of memory T cells, the predominant lymphocyte subset in atherosclerotic plaque. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CHARLESTOWN,MA 02129. NHLBI,MOL HEMATOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV VASC RES,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-54202, HL-475646, HL-36028] NR 47 TC 54 Z9 56 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1996 VL 79 IS 6 BP 1205 EP 1215 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA VV612 UT WOS:A1996VV61200016 PM 8943959 ER PT J AU Cooper, PJ Guderian, RH Prakash, D Remick, DG Espinel, I Nutman, TB Taylor, DW Griffin, GE AF Cooper, PJ Guderian, RH Prakash, D Remick, DG Espinel, I Nutman, TB Taylor, DW Griffin, GE TI RANTES in onchocerciasis: Changes with ivermectin treatment SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE onchocerciasis; ivermectin; chemokines; RANTES; cytokines ID TUMOR-NECROSIS-FACTOR; CHEMOKINE RANTES; MAZZOTTI REACTION; CYTOKINE RANTES; HUMAN-MONOCYTES; MESSENGER-RNA; CELL-LINE; T-CELL; INTERLEUKIN-8; EOSINOPHIL AB Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-alpha were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P < 0.001) and lymphoedema (P < 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo. C1 UNIV LONDON ST GEORGES HOSP,SCH MED,DIV INFECT DIS,LONDON SW17 0RE,ENGLAND. HOSP VOZANDES,ONCHOCERCIASIS CONTROL PROGRAMME,QUITO,ECUADOR. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV EDINBURGH,CTR TROP VET MED,EDINBURGH,MIDLOTHIAN,SCOTLAND. RP Cooper, PJ (reprint author), NIH,PARASIT DIS LAB,BLDG 14 ROOM 126,BETHESDA,MD 20892, USA. FU Wellcome Trust NR 48 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD DEC PY 1996 VL 106 IS 3 BP 462 EP 467 DI 10.1046/j.1365-2249.1996.d01-868.x PG 6 WC Immunology SC Immunology GA VV606 UT WOS:A1996VV60600007 PM 8973613 ER PT J AU Levine, SJ AF Levine, SJ TI Pneumocystis carinii SO CLINICS IN CHEST MEDICINE LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; HIV-INFECTED PATIENTS; AEROSOLIZED PENTAMIDINE PROPHYLAXIS; SERUM LACTATE-DEHYDROGENASE; MAJOR SURFACE GLYCOPROTEIN; IN-HOSPITAL MORTALITY; POLYMERASE CHAIN-REACTION; TUMOR-NECROSIS-FACTOR; CULTURED LUNG-CELLS AB Improved understanding of Pneumocystis carinii, in particular the widespread use of chemoprophylaxis, has resulted in a declining incidence of infection in patients infected with HIV since the late 1980s. Despite these advances, P. carinii pneumonia continues to represent an important cause of pulmonary disease in HIV-seropositive individuals who do not receive chemoprophylaxis or when breakthrough episodes occur. This article reviews the history, biology, clinical manifestations, prognostic markers, therapy, and chemoprophylaxis of P. carinii pneumonia in HIV-seropositive patients. RP Levine, SJ (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,10 CTR DR,MSC 1662,BETHESDA,MD 20892, USA. NR 341 TC 24 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1996 VL 17 IS 4 BP 665 EP & DI 10.1016/S0272-5231(05)70339-7 PG 32 WC Respiratory System SC Respiratory System GA WD001 UT WOS:A1996WD00100005 PM 9016371 ER PT J AU Karni, A AF Karni, A TI The acquisition of perceptual and motor skills: A memory system in the adult human cortex SO COGNITIVE BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 9th Toyota Conference on the Brain and Mind CY DEC 05-08, 1995 CL MIKKABI, JAPAN SP Toyota DE memory; cortex, human; plasticity; procedural learning ID PRIMARY VISUAL-CORTEX; CORTICAL PLASTICITY; DISCRIMINATION; IMPROVEMENT; ORIENTATION; MECHANISMS; NEURONS; CATS; NORADRENALINE; ORGANIZATION C1 WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. RP Karni, A (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,NIH,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 50 TC 124 Z9 125 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD DEC PY 1996 VL 5 IS 1-2 BP 39 EP 48 DI 10.1016/S0926-6410(96)00039-0 PG 10 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA WH807 UT WOS:A1996WH80700005 ER PT J AU Colby, CL Duhamel, JR AF Colby, CL Duhamel, JR TI Spatial representations for action in parietal cortex SO COGNITIVE BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 9th Toyota Conference on the Brain and Mind CY DEC 05-08, 1995 CL MIKKABI, JAPAN SP Toyota DE spatial perception; parietal cortex ID VISUAL AREA MT; MACAQUE MONKEY; INFERIOR AREA-6; CORTICAL CONNECTIONS; INTRAPARIETAL AREA; ASSOCIATION CORTEX; SPACE; RESPONSES; ATTENTION; MOVEMENTS RP Colby, CL (reprint author), NEI,SENSORIMOTOR RES LAB,NIH,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 34 TC 117 Z9 118 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD DEC PY 1996 VL 5 IS 1-2 BP 105 EP 115 DI 10.1016/S0926-6410(96)00046-8 PG 11 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA WH807 UT WOS:A1996WH80700012 ER PT J AU Hiraiwa, M Saitoh, M Uda, Y Azuma, N Martin, BM Kishimoto, Y OBrien, JS AF Hiraiwa, M Saitoh, M Uda, Y Azuma, N Martin, BM Kishimoto, Y OBrien, JS TI A sialidase complex from chicken liver: Characterization of a multienzyme complex with beta-galactosidase and carboxypeptidase SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE sialidase; neuraminidase; beta-galactosidase; carboxypeptidase; protective protein; lysosomal enzyme; enzyme complex ID HUMAN PLACENTAL SIALIDASE; LYSOSOMAL NEURAMINIDASE; PROTECTIVE PROTEIN; PURIFICATION; CDNA; EXPRESSION; CLONING AB Mammalian lysosomal sialidase exists as an enzyme complex with beta-galactosidase and carboxypep tidase, so called ''protective protein.'' In this article, we report that chicken sialidase also occurs as a complex with beta-galactosidase and protective protein. The purified sialidase complex had a molecular weight > 700 kDa on gel filtration and showed four protein components of 76, 65, 54 and 48 kDa on SDS-PAGE under nonreducing conditions. N-Terminal sequences of the 65- and 48 kDa proteins were homologous to human lysosomal a galactosidase and protective protein precursor, respectively. The purified sialidase complex also had carboxypeptidase activity. Both sialidase and carboxypeptidase activities were precipitated together by an antibody against chicken beta-galactosidase. The complex reversibly dissociated into 120-kDa beta-galactosidase dimer and 100-kDa carboxypeptidase dimer at pH 7.5, but the sialidase irreversibly inactivated during the depolymerization. These findings indicate that chicken sialidase exists as a multienzyme complex, by which the sialidase activity appears to be stabilized. Copyright (C) 1996 Elsevier Science Inc. C1 NIIGATA COLL PHARM,DEPT HLTH CHEM,NIIGATA 95021,JAPAN. NIMH,SECT MOL NEUROGENET,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP Hiraiwa, M (reprint author), UNIV CALIF SAN DIEGO,SCH MED,CTR MOL GENET,DEPT NEUROSCI,9500 GILMAN DR,LA JOLLA,CA 92093, USA. NR 20 TC 7 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD DEC PY 1996 VL 115 IS 4 BP 541 EP 546 DI 10.1016/S0305-0491(96)00191-5 PG 6 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA VZ241 UT WOS:A1996VZ24100016 ER PT J AU Huang, XQ Zhang, JH AF Huang, XQ Zhang, JH TI Methods for comparing a DNA sequence with a protein sequence SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID LINEAR-SPACE; ALGORITHM; SUBSEQUENCES; ALIGNMENT AB We describe two methods for constructing an optimal global alignment of and an optimal local alignment between a DNA sequence and a protein sequence. The alignment model of the methods addresses the problems of frameshifts and introns in the DNA sequence. The methods require computer memory proportional to the sequence lengths, so they can rigorously process very huge sequences. The simplified versions of the methods were implemented as computer programs named NAP and LAP. The experimental results demonstrate that the programs are sensitive and powerful tools for finding genes by DNA-protein sequence homology. C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, NIH, BETHESDA, MD 20894 USA. RP MICHIGAN TECHNOL UNIV, DEPT COMP SCI, 1400 TOWNSEND DR, HOUGHTON, MI 49931 USA. NR 14 TC 54 Z9 56 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD DEC PY 1996 VL 12 IS 6 BP 497 EP 506 PG 10 WC Computer Science, Interdisciplinary Applications SC Computer Science GA WE386 UT WOS:A1996WE38600008 PM 9021268 ER PT J AU Rio, DE Rawlings, RR Kerich, MJ Momenan, R Eckardt, MJ AF Rio, DE Rawlings, RR Kerich, MJ Momenan, R Eckardt, MJ TI Statistical methods in the Fourier domain to enhance and classify images SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; ANATOMICAL LOCALIZATION; BRAIN; PET; DISORDERS; DISEASE; REGION AB A mathematical model, for which rigorous methods of statistical inference are available, is described and techniques for image enhancement and linear discriminant analysis of groups are developed. Since the gray values of neighboring pixels in tomographically produced medical images are spatially correlated, the calculations are carried out in the Fourier domain to insure statistical independence of the variables. Furthermore, to increase the power of statistical tests the known spatial covariance was used to specify constraints in the spectral domain. These methods were compared to statistical procedures carried out in the spatial domain. Positron emission tomography (PET) images of alcoholics with organic brain disorders were compared by these techniques to age-matched normal volunteers. Although these techniques are employed to analyze group characteristics of functional images, they provide a comprehensive set of mathematical and statistical procedures in the spectral domain that on also be applied to images of other modalities, such as computed tomography (CT) or magnetic resonance imaging(MRI). (C) 1996 Academic Press, Inc. C1 MEDDATA RES,MCLEAN,VA 22102. RP Rio, DE (reprint author), NIAAA,CLIN STUDIES LAB,NIH,10 CTR DR,MSC 1256,BETHESDA,MD 20892, USA. NR 39 TC 1 Z9 1 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 0010-4809 J9 COMPUT BIOMED RES JI Comput. Biomed. Res. PD DEC PY 1996 VL 29 IS 6 BP 438 EP 465 DI 10.1006/cbmr.1996.0033 PG 28 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA WD584 UT WOS:A1996WD58400002 PM 9012568 ER PT J AU Freedman, L Anderson, G Kipnis, V Prentice, R Wang, CY Rossouw, J Wittes, J DeMets, D AF Freedman, L Anderson, G Kipnis, V Prentice, R Wang, CY Rossouw, J Wittes, J DeMets, D TI Approaches to monitoring the results of long-term disease prevention trials: Examples from the women's health initiative SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trials; disease prevention; data and safety monitoring; multiple endpoints; stopping rules ID CLINICAL-TRIALS; ISSUES AB We contrast monitoring therapeutic trials with monitoring prevention trials. We argue that in monitoring prevention trials one should place more emphasis on formally defined global measures of health, not simply on a single targeted disease, particularly when an intervention may reduce the incidence of some diseases but increase the incidence of others. We describe one approach, illustrated by the Women's Health Initiative. For each of several sets of hypothetical interim results (''scenarios''), members of the Data and Safety Monitoring Committee (DSMC) were asked whether they would continue or stop the trial. In parallel with this exercise, various statistical methods of monitoring that are based on (1) the primary targeted disease, (2) a combination of various disease outcomes, or (3) a mixture of both were applied to these scenarios. One objective was to find a statistical approach that mirrors the majority view of the DSMC. A second objective was to stimulate discussion among DSMC members in preparation for their task of monitoring the trial as the real data become available. We found that no single method fully matched the majority vote of the DSMC. However, a mixed approach requiring the primary outcome to be significant and the global index to be ''supportive,'' with separate monitoring of adverse effects, corresponded with the majority vote quite well. This approach maintains the emphasis on the primary hypothesis while assuring that broader safety and ethical issues of multiple diseases are incorporated. (C) Elsevier Science Inc., 1996 C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NIH,BETHESDA,MD 20892. STAT COLLABORAT,WASHINGTON,DC. UNIV WISCONSIN,MADISON,WI. RP Freedman, L (reprint author), NCI,BIOMETRY BRANCH,DCPC,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20892, USA. OI Anderson, Garnet/0000-0001-5087-7837 NR 9 TC 48 Z9 49 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1996 VL 17 IS 6 BP 509 EP 525 DI 10.1016/S0197-2456(96)00016-5 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VY955 UT WOS:A1996VY95500005 PM 8974210 ER PT J AU Korn, EL Simon, R AF Korn, EL Simon, R TI Data monitoring committees and problems of lower-than-expected accrual or event rates SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trials; interim analysis; conditional power; stochastic curtailment ID CONDITIONAL POWER CALCULATIONS; CLINICAL-TRIALS; INTERIM ANALYSES; STOPPING RULES; SIZE; EXPERIENCE; DECISION; WHETHER; DESIGN; TESTS AB Data monitoring committees for randomized clinical trials must frequently decide what action, if any, is required for trials whose accrual has been slower than expected, or whose event rates have been less than expected. We discuss in this article some of the practical issues concerning modifying or closing such trials, including what data and analyses could be helpful to the data monitoring committee in their delibrations. (C) Elsevier Science Inc. 1996. RP Korn, EL (reprint author), NCI,BIOMETR RES BRANCH,EPN-739,BETHESDA,MD 20892, USA. NR 38 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1996 VL 17 IS 6 BP 526 EP 535 DI 10.1016/S0197-2456(96)00088-8 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VY955 UT WOS:A1996VY95500006 PM 8974211 ER PT J AU Makalowski, W Recipon, H AF Makalowski, W Recipon, H TI Web alert - Pharmaceutical biotechnology SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article RP Makalowski, W (reprint author), NATL CTR BIOTECHNOL INFORMAT,NIH,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD DEC PY 1996 VL 7 IS 6 BP 667 EP 667 DI 10.1016/S0958-1669(96)80080-2 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VU443 UT WOS:A1996VU44300014 PM 8939647 ER PT J AU Boguski, MS Cox, DR Myers, RM AF Boguski, MS Cox, DR Myers, RM TI Genomes and evolution - Overview SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 STANFORD UNIV,DEPT GENET,SCH MED,STANFORD,CA 94305. STANFORD UNIV,STANFORD HUMAN GENOME CTR,SCH MED,STANFORD,CA 94305. RP Boguski, MS (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8S-810,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1996 VL 6 IS 6 BP 683 EP 685 DI 10.1016/S0959-437X(96)80020-7 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VZ215 UT WOS:A1996VZ21500001 ER PT J AU Leipe, DD AF Leipe, DD TI Biodiversity, genomes, and DNA sequence databases SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID GENE CONTENT; CHLOROPLAST GENOME; MITOCHONDRIAL-DNA; RIBOSOMAL DNA; ORGANISMS; EVOLUTION; PROJECT; ORGANIZATION; PHYLOGENY; BACTERIA AB There are similar to 1.4 million organisms on this planet that have been described morphologically but there is no comparable coverage of biodiversity at the molecular level. Little more than 1% of the known species have been subject to any molecular scrutiny and eukaryotic genome projects have focused on a group of closely related model organisms. The past year, however, has seen an similar to 80% increase in the number of species represented in sequence databases and the completion of the sequencing of three prokaryotic genomes. Large-scale sequencing projects seem set to begin coverage of a wider range of the eukaryotic diversity, including green plants, microsporidians and diplomonads. RP Leipe, DD (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20984, USA. NR 49 TC 5 Z9 6 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1996 VL 6 IS 6 BP 686 EP 691 DI 10.1016/S0959-437X(96)80021-9 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VZ215 UT WOS:A1996VZ21500002 PM 8994837 ER PT J AU Koonin, EV Mushegian, AR AF Koonin, EV Mushegian, AR TI Complete genome sequences of cellular life forms: Glimpses of theoretical evolutionary genomics SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID YEAST CHROMOSOME-III; PROTEINS AB The availability of complete genome sequences of cellular life forms creates the opportunity to explore the functional content of the genomes and evolutionary relationships between them at a new qualitative level. With the advent of these sequences, the construction of a minimal gene set sufficient for sustaining cellular life and reconstruction of the genome of the last common ancestor of bacteria, eukaryotes, and archaea become realistic, albeit challenging, research projects. A version of the minimal gene set for modern-type cellular life derived by comparative analysis of two bacterial genomes, those of Haemophilus influenzae and Mycoplasma genitalium, consists of similar to 250 genes. A comparison of the protein sequences encoded in these genes with those of the proteins encoded in the complete yeast genome suggests that the last common ancestor of all extant life might have had an RNA genome. RP Koonin, EV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. OI Mushegian, Arcady/0000-0002-6809-9225 NR 39 TC 41 Z9 42 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1996 VL 6 IS 6 BP 757 EP 762 DI 10.1016/S0959-437X(96)80032-3 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VZ215 UT WOS:A1996VZ21500013 PM 8994848 ER PT J AU Bassett, DE Basrai, MA Connelly, C Hyland, KM Kitagawa, K Mayer, ML Morrow, DM Page, AM Resto, VA Skibbens, RV Hieter, P AF Bassett, DE Basrai, MA Connelly, C Hyland, KM Kitagawa, K Mayer, ML Morrow, DM Page, AM Resto, VA Skibbens, RV Hieter, P TI Exploiting the complete yeast genome sequence SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID ATAXIA-TELANGIECTASIA; GENE-EXPRESSION; HOMOLOG AB The completion of the genome sequence Of the budding yeast Saccharomyces cerevisiae marks the dawn of an exciting new era in eukaryotic biology that will bring with it a new understanding of yeast, other model organisms, and human beings. This body of sequence data benefits yeast researchers by obviating the need for piecemeal sequencing of genes, and allows researchers working with other organisms to tap into experimental advantages inherent in the yeast system and learn from functionally characterized yeast gene products which are their proteins of interest. In addition, the yeast post-genome sequence era is serving as a testing ground for powerful new technologies, and proven experimental approaches are being applied for the first time in a comprehensive fashion on a complete eukaryotic gene repertoire. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. RI Resto, Vicente/D-9891-2014 NR 20 TC 19 Z9 20 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1996 VL 6 IS 6 BP 763 EP 766 DI 10.1016/S0959-437X(96)80033-5 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VZ215 UT WOS:A1996VZ21500014 PM 8994849 ER PT J AU Metzger, H AF Metzger, H TI On hubris and humility SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID AGGREGATION; RECEPTOR; IGE RP Metzger, H (reprint author), NIAMS,NIH,BLDG 10,ROOM 9N-228,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 1996 VL 8 IS 6 BP 763 EP 765 DI 10.1016/S0952-7915(96)80001-X PG 3 WC Immunology SC Immunology GA VZ197 UT WOS:A1996VZ19700001 PM 8994852 ER PT J AU Beaven, MA Baumgartner, RA AF Beaven, MA Baumgartner, RA TI Downstream signals initiated in mast cells by Fc epsilon RI and other receptors SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID AFFINITY IGE RECEPTOR; CYTOSOLIC PHOSPHOLIPASE A(2); BASOPHILIC LEUKEMIA-CELLS; PROTEIN-KINASE-C; TYROSINE PHOSPHORYLATION; CROSS-LINKING; NUCLEAR FACTOR; RBL-2H3 CELLS; ACTIVATION; PATHWAYS AB The significant contributions this past year to our understanding of IgE receptor (Fc epsilon RI) signaling in mast cells include studies with truncated Syk in a vaccinia expression system and Syk-negative variants of rat basophilic (RBL-2H3) cells. These studies demonstrate an essential role for Syk in initiating signals for secretion and release of arachidonic acid via phospholipase A(2) and mitogen-activated protein kinase. A newly recognized addition to the repertoire of Fc epsilon RI-mediated signaling systems is the activation of sphingosine kinase, which contributes to calcium mobilization in mast cells. Advances have been made in our understanding of other receptors that regulate proliferation and differentiation of mast cells, and in our understanding of the ability of mast cells to mount acquired and acute responses to antigenic and bacterial challenge. RP Beaven, MA (reprint author), NHLBI,MOL IMMUNOL LAB,NIH,ROOM 8N109,BLDG 10,BETHESDA,MD 20892, USA. NR 66 TC 68 Z9 68 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 1996 VL 8 IS 6 BP 766 EP 772 DI 10.1016/S0952-7915(96)80002-1 PG 7 WC Immunology SC Immunology GA VZ197 UT WOS:A1996VZ19700002 PM 8994853 ER PT J AU Mills, JL Conley, MR AF Mills, JL Conley, MR TI Folic acid to prevent neural tube defects: Scientific advances and public health issues SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article ID PERICONCEPTIONAL VITAMIN SUPPLEMENTATION; RISK FACTOR; METHYLENETETRAHYDROFOLATE REDUCTASE; HOMOCYSTEINE METABOLISM; FOLATE AB Folic acid prevents some neural tube defects by correcting abnormal homocysteine metabolism. A defective gene coding for a homocysteine-related enzyme has been shown in people with neural tube defects. An extensive educational campaign will be required to alert women to the need to take 0.4 mg/day of folic acid during their childbearing years. RP Mills, JL (reprint author), NICHHD,PEDIAT EPIDEMIOL SECT,NIH,DIV EPIDEMIOL STAT & PREVENT RES,6100 BLDG,ROOM 7B03,BETHESDA,MD 20892, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD DEC PY 1996 VL 8 IS 6 BP 394 EP 397 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VZ204 UT WOS:A1996VZ20400002 PM 8979009 ER PT J AU Karavanova, ID Dove, LF Resau, JH Perantoni, AO AF Karavanova, ID Dove, LF Resau, JH Perantoni, AO TI Conditioned medium from a rat ureteric bud cell line in combination with bFGF induces complete differentiation of isolated metanephric mesenchyme SO DEVELOPMENT LA English DT Article DE kidney; induction; tubulogenesis; Wnt genes; FGF ID HEPATOCYTE GROWTH-FACTOR; KIDNEY DEVELOPMENT; MESSENGER-RNA; TRANSFILTER INDUCTION; EXPRESSION PATTERNS; RET PROTOONCOGENE; MOUSE DEVELOPMENT; TYROSINE KINASE; TUBULES; SYSTEM AB Differentiation of metanephric mesenchyme is triggered by an inductive signal(s) from the epithelial ureteric bud, As a result of this induction, most of the metanephric mesenchyme converts into epithelium of a nephron, We have developed and characterized an explant culture system, in which metanephric mesenchyme can grow and completely differentiate in vitro in the absence of an inductive tissue, When separated 13 dpc rat metanephric mesenchymes were cultured in serum-free conditioned medium from a rat ureteric bud cell line (RUB1) in the presence of bFGF and TGF alpha, they were induced to differentiate into nephron epithelia and glomeruli-like structures, The nephric type of differentiation was confirmed by both morphological and molecular criteria and paralleled the developmental changes of nephron differentiation in vivo, Expression patterns of brush-border antigen as well as molecular markers of kidney differentiation Wt1, Lim1, Hgf and c-met, c-ret, Shh, Wnt4, Wnt7b, and Wnt11 were analyzed in explants by whole mount and tissue section in situ hybridization following 1-9 days in culture, The expression of secreted patterning molecules Bmp7 and Wnt7b, but not Shh or Wnt11, were demonstrated by RT-PCR and northern blot hybridization with RNA from the RUB1 cells, Our culture system lends itself to examining the relevance of these and other signaling molecules required for nephron differentiation. C1 NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Karavanova, ID (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 47 TC 86 Z9 89 U1 1 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 DEC PY 1996 VL 122 IS 12 BP 4159 EP 4167 PG 9 WC Developmental Biology SC Developmental Biology GA WC554 UT WOS:A1996WC55400046 PM 9012535 ER PT J AU Mayes, LC Bornstein, MH Chawarska, K Haynes, OM Granger, RH AF Mayes, LC Bornstein, MH Chawarska, K Haynes, OM Granger, RH TI Impaired regulation of arousal in 3-month-old infants exposed prenatally to cocaine and other drugs SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID ATTENTION; HABITUATION; STIMULANTS; ABUSERS; BRAIN AB This study investigated relations between drug exposure, particularly cocaine, and infants' regulation of arousal in response to novelty. Sixty-three infants-36 cocaine exposed and 27 non-cocaine exposed-participated at 3 months of age in a novel-repeat stimulus presentation procedure. Arousal was operationalized in terms of infant behavioral state, affective expressiveness, and attention to the stimulus. Infants were tested and infant behaviors were scored by experimenters blind to the drug exposure status of the infant. There were no differences between the two groups in baseline behavioral state or affective expression before the presentation of novel stimuli. Compared to the non-cocaine-exposed group, infants exposed prenatally to cocaine and other drugs were more likely to exhibit a crying state and to display negative affect on novel stimulus presentations. There were no group differences in the amount of looking toward the stimulus. Both groups showed less crying and negative affect when stimuli were presented a second time, but decrements were consistently greater for the cocaine-exposed group. These results obtained when group differences were controlled for sociodemographic and perinatal variables. Sources of differences in the regulation of arousal in cocaine-exposed and non-cocaine-exposed infants are discussed, and impairments in the regulation of arousal in cocaine-exposed infants are considered in a framework of predictive implications for children's social and cognitive development. C1 NICHHD,BETHESDA,MD 20892. RP Mayes, LC (reprint author), YALE CHILD STUDY CTR,230 S FRONTAGE RD,NEW HAVEN,CT 06510, USA. NR 63 TC 62 Z9 62 U1 3 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 1996 VL 8 IS 1 BP 29 EP 42 PG 14 WC Psychology, Developmental SC Psychology GA TW641 UT WOS:A1996TW64100004 ER PT J AU ZahnWaxler, C Schmitz, S Fulker, D Robinson, J Emde, R AF ZahnWaxler, C Schmitz, S Fulker, D Robinson, J Emde, R TI Behavior problems in 5-year-old monozygotic and dizygotic twins: Genetic and environmental influences, patterns of regulation, and internalization of control SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CONDUCT PROBLEMS; CHILDHOOD; PSYCHOPATHOLOGY; DISORDERS AB Genetic influence on externalizing problems, internalizing problems, and attentional/activity problems in 5-year-olds was consistently identified across informants and assessment contexts. Effects of the shared environment were identified as well but with less consistency (i.e., only from parents, not teachers, and more from father than mother reports). Correlations between observed patterns of regulation at ages 3, 4, and 5 years and behavior problems at age 5 years were often significant, but low in magnitude and specific to teacher reports. Adaptive internalization of control at each age (e.g., frustration tolerance, capacity to attend and focus, good impulse control) predicted fewer externalizing problems. Internalization of standards, reflected in children's moral themes, understanding of reciprocity, and constructive social problem solving, also were sometimes associated with fewer problems. Significant correlations were low in magnitude and again specific to teacher reports. Externalizing problems were more prevalent for boys than girls, and regulation (i.e., internalization of control and standards) was more characteristic of girls than boys. C1 NIMH, BETHESDA, MD 20892 USA. UNIV COLORADO, INST BEHAV GENET, BOULDER, CO 80309 USA. UNIV COLORADO, MED CTR, DENVER, CO 80202 USA. NR 59 TC 63 Z9 63 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 1996 VL 8 IS 1 BP 103 EP 122 PG 20 WC Psychology, Developmental SC Psychology GA TW641 UT WOS:A1996TW64100008 ER PT J AU Post, RM Weiss, SRB Leverich, GS George, MS Frye, M Ketter, TA AF Post, RM Weiss, SRB Leverich, GS George, MS Frye, M Ketter, TA TI Developmental psychobiology of cyclic affective illness: Implications for early therapeutic intervention SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID CEREBRAL BLOOD-FLOW; CORTICOTROPIN-RELEASING FACTOR; PIMOZIDE BLOCKS ESTABLISHMENT; SEASONAL AFFECTIVE-DISORDER; BIPOLAR DISORDER; MESSENGER-RNA; ELECTRICAL-STIMULATION; GLUCOSE-METABOLISM; MAJOR DEPRESSION; KINDLED SEIZURES AB The recurrent affective disorders are discussed from the perspective of accumulating inherited and experiential effects on gene expression. Stress and episodes of affective illness are viewed as leaving biochemical and microstructural residues in the central nervous system (CNS) in relation to their patterning, severity, and recurrence. Comorbid factors such as substance abuse and developmental disturbances may also interact with these illness-related variables. In addition to the primary pathological processes, secondary adaptive changes can also be induced, which, in concert with pharmacological interventions, may be sufficient to counter episode occurrences and illness progression. We postulate that the balance of primary pathological and secondary adaptive changes at multiple levels of CNS regulation accounts for recurrence and cyclicity in the affective disorders. The importance of early, effective, long-term interventions in the recurrent affective disorders and the therapeutic potential of several new treatment modalities including repeated transcranial magnetic stimulation (rTMS) are discussed. RP Post, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,10 CTR DR,MSC 1272,BETHESDA,MD 20892, USA. NR 146 TC 39 Z9 39 U1 6 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 1996 VL 8 IS 1 BP 273 EP 305 PG 33 WC Psychology, Developmental SC Psychology GA TW641 UT WOS:A1996TW64100017 ER PT J AU Nelson, RG Hanson, RL Pettitt, DJ Knowler, WC Bennett, PH AF Nelson, RG Hanson, RL Pettitt, DJ Knowler, WC Bennett, PH TI Survival during renal replacement therapy for diabetic end-stage renal disease in Pima Indians SO DIABETES CARE LA English DT Article ID AMBULATORY PERITONEAL-DIALYSIS; MEXICAN-AMERICANS; NATIVE-AMERICANS; MORTALITY; HEMODIALYSIS; PREDICTORS; MELLITUS; RATES AB OBJECTIVE - To examine survival in Pima Indians receiving renal replacement therapy for end-stage renal disease attributed to NIDDM. RESEARCH DESIGN AND METHODS - Vital status through 1994 was determined for 136 diabetic Pima Indians from the Gila River Indian Community who began renal replacement therapy between 1973 and 1990. RESULTS - Median survival from the onset of renal replacement therapy was 39 months (95% CI, 31-54), 31 months (95% CI, 11-48) in those who began treatment between 1973 and 1981, and 44 months (95% CI, 32-56) in those who began treatment between 1982 and 1990 (P = 0.020). During these periods, mean age at onset of treatment increased from 53.3 to 56.1 years (P = 0.166), and mean duration of diabetes at the onset of treatment increased from 16.5 to 20.2 years (P = 0.003). After adjustment for sex, duration of diabetes, initial dialysis type, and kidney transplantation by an age-stratified proportional-hazards analysis, the death rate after starting renal replacement therapy in the second half of the study was 0.54 times (95% CI, 0.33-0.88) that in the first half. If this analysis was restricted to those who survived at least 90 days of therapy, the difference between the time periods was diminished (death rate ratio = 0.76; 95% CI, 0.43-1.32). CONCLUSIONS - Survival in Pima Indians receiving renal replacement therapy improved significantly over the study despite an increase in the average age and diabetes duration of those beginning dialysis. Much of the improvement in survival is attributable to a reduction in the number of deaths within the first 90 days of therapy. The median survival of 47 months in Pima Indians < 65 years old at the initiation of therapy is substantially longer than the 30 months reported in blacks and 16 months reported in whites of similar age with NIDDM. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,PHOENIX,AZ. RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [N01-DK-2-2209] NR 30 TC 12 Z9 12 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 DEC PY 1996 VL 19 IS 12 BP 1333 EP 1337 DI 10.2337/diacare.19.12.1333 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU770 UT WOS:A1996VU77000004 PM 8941459 ER PT J AU Narayan, KMV Pettitt, DJ AF Narayan, KMV Pettitt, DJ TI Glycosylated hemoglobin in pregnancy SO DIABETES CARE LA English DT Letter C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 5 TC 0 Z9 0 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 DEC PY 1996 VL 19 IS 12 BP 1455 EP 1455 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU770 UT WOS:A1996VU77000032 PM 8941487 ER PT J AU Striker, GE Striker, LJ AF Striker, GE Striker, LJ TI Recent advances in diabetic nephropathy: How big a culprit is glucose? SO DIABETES & METABOLISM LA English DT Review ID GLYCOSYLATION END-PRODUCTS; MESSENGER-RNA EXPRESSION; EXTRACELLULAR-MATRIX; HUMAN GLOMERULOSCLEROSIS; GENE-EXPRESSION; MESANGIAL CELLS; IV COLLAGEN; RATS; DISEASE; INSULIN RP Striker, GE (reprint author), NIDDK,RENAL CELL BIOL SECT,NIH,BETHESDA,MD 20892, USA. NR 37 TC 1 Z9 1 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0338-1684 J9 DIABETES METAB JI Diabetes Metab. PD DEC PY 1996 VL 22 IS 6 BP 407 EP 414 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW591 UT WOS:A1996VW59100003 PM 8985648 ER PT J AU McCormack, LJ Nagi, DK Stickland, MH Mansfield, MW MohamedAli, V Yudkin, JS Knowler, WC Grant, PJ AF McCormack, LJ Nagi, DK Stickland, MH Mansfield, MW MohamedAli, V Yudkin, JS Knowler, WC Grant, PJ TI Promoter (4G/5G) plasminogen activator inhibitor-1 genotype in Pima Indians: Relationship to plasminogen activator inhibitor-1 levels and features of the insulin resistance syndrome SO DIABETOLOGIA LA English DT Article DE plasminogen activator inhibitor-1; fibrinolysis; Pima Indians; polymorphism; genetic; diabetes mellitus; non-insulin-dependent ID DEPENDENT DIABETES-MELLITUS; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; FIBRINOLYTIC-ACTIVITY; ENDOTHELIAL-CELLS; PLASMA-INSULIN; RISK-FACTORS; PAI-1 GENE; CARDIOVASCULAR-DISEASE; HEART-DISEASE AB Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, mean age 46.6, range 34-68 years) the promoter genotype frequencies were 23.0 % for 4G/4G, 49.8 % for 4G/5G and 27.2 % for 5G/5G compared to 35.4 %, 50.8 % and 13.8 % respectively (chi 2 = 15.3, 2 df, p < 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p < 0.0001), body mass index (r = 0.24, p < 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promoter genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians. C1 EDNA COATES DIABET CTR, WAKEFIELD, ENGLAND. UCL, WHITTINGTON HOSP, SCH MED, DEPT MED, LONDON, ENGLAND. NIDDK, NIH, PHOENIX, AZ USA. RP McCormack, LJ (reprint author), GEN INFIRM, UNIT MOL VASC MED, RES SCH MED, G FLOOR, MARTIN WING, LEEDS LS1 3EX, W YORKSHIRE, ENGLAND. RI Yudkin, John/C-1988-2008 NR 51 TC 32 Z9 36 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 1996 VL 39 IS 12 BP 1512 EP 1518 DI 10.1007/s001250050606 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW215 UT WOS:A1996VW21500014 PM 8960834 ER PT J AU Mangia, A Chung, YH Hoofnagle, JH Birkenmeyer, L Mushahwar, I DiBisceglie, AM AF Mangia, A Chung, YH Hoofnagle, JH Birkenmeyer, L Mushahwar, I DiBisceglie, AM TI Pathogenesis of chronic liver disease in patients with chronic hepatitis B virus infection without serum HBeAg SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE hepatitis B; variant; HBeAg negative ID PRECORE REGION; E-ANTIGEN; FULMINANT-HEPATITIS; INTERFERON; MUTANTS; DNA; NUCLEOTIDE; CARRIERS AB Chronic hepatitis B in patients lacking hepatitis B e antigen has been attributed to a hepatitis B virus variant (G-to-A mutation at nucleotide 1896 in the precore region of the genome). We therefore assessed the frequency and significance of this variant among 43 United States patients (10 with chronic hepatitis B seropositive for e antigen, 19 seronegative for e antigen, and 14 healthy carriers). Sera were tested for HBV DNA by polymerase chain reaction and branched DNA assay. The A(1896) variant was detected by direct sequencing and ligase chain reaction. Serum HBV DNA was more frequently found among patients with e antigen-positive than e antigen-negative chronic hepatitis B. Viral titers were generally higher in those with e antigen. None of the e antigen-positive and only 24% of e antigen-negative patients harbored the A(1896) variant. Patients infected with the variant were more often Asian, had had hepatitis B for longer and had higher levels of viral DNA than HBeAg-negative patients with the wild-type virus. The A(1896) variant was found exclusively in patients infected with HBV genotypes C and D. Thus, the A(1896) variant is uncommon in the United States. The activity of liver disease appears to be more closely related to the level of HBV replication than the presence of mutations at nucleotide 1896 in the genome. C1 NIDDKD,LIVER DIS SECT,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. ABBOTT LABS,N CHICAGO,IL 60064. NR 18 TC 35 Z9 37 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 1996 VL 41 IS 12 BP 2447 EP 2452 DI 10.1007/BF02100141 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WB788 UT WOS:A1996WB78800026 PM 9011456 ER PT J AU Clausse, N Jackers, P Jares, P Joris, B Sobel, ME Castronovo, V AF Clausse, N Jackers, P Jares, P Joris, B Sobel, ME Castronovo, V TI Identification of the active gene coding for the metastasis-associated 37LRP/p40 multifunctional protein SO DNA AND CELL BIOLOGY LA English DT Article ID AFFINITY LAMININ RECEPTOR; MESSENGER-RNA; BINDING-PROTEIN; TRANSCRIPTION FACTORS; PROMOTER REGION; MAMMALIAN-CELLS; CANCER-CELLS; RAT-LIVER; 5' REGION; MOUSE AB A 37LRP/p40 polypeptide is of major interest because it is consistently up-regulated in cancer cells in correlation with their invasive and metastatic phenotype, Furthermore, this polypeptide presents intriguing multifunctional properties because it has been characterized as the precursor of the metastasis-associated 67-kD laminin receptor (67LR) and as a cytoplasmic ribosomal-associated protein. The isolation of the 37LRP/p40 gene is a prerequisite for identifying the molecular mechanisms responsible for the constant up-regulation of the 67LR expression in cancer cells, To date, the active 37LRP/p40 gene has never been identified in any species due to the existence of multiple pseudogenes in most vertebrates genomes. In this study, we report for the first time the gene structure and potential regulatory sequences of the 37 LRP/p40 gene, The chicken genome was selected to undergo this characterization because it is the only known vertebrate that bears a single 37 LRP/p40 gene copy, The 37 LRP/p40 active gene is composed of 7 exons and 6 introns and bears features characteristic of a ribosomal protein gene. It does not bear a classical TATA box and it exhibits several transcription initiation sites as demonstrated by RNase protection assay and primer extension. Analysis of potential regulatory regions suggests that gene expression is driven not only by the 5' genomic region but also by the 5' untranslated and intron 1 sequences. On the basis of gene structure and extensive protein evolutionary study, we found that the carboxyterminal domain of the protein is a conserved lock-and-key structure/function domain that could be involved in the biosynthesis of the higher-molecular-weight 67-kD laminin receptor in vertebrates, whereas the central core of the protein would be responsible for the ribosome associated function. The first identification of the active 37LRP/p40 gene presented in this study is a critical step toward the isolation of the corresponding human gene and the understanding of the molecular mechanisms involved in the up-regulation of its expression during tumor invasion and metastasis. C1 UNIV LIEGE,METASTASIS RES LAB,B-4000 LIEGE 1,BELGIUM. UNIV LIEGE,CTR INGN PROT,B-4000 LIEGE,BELGIUM. NCI,MOL PATHOL SECT,BETHESDA,MD 20892. NR 62 TC 33 Z9 37 U1 0 U2 1 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 DEC PY 1996 VL 15 IS 12 BP 1009 EP 1023 DI 10.1089/dna.1996.15.1009 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA WA177 UT WOS:A1996WA17700001 PM 8985115 ER PT J AU Srivastava, M AF Srivastava, M TI Xenopus cytochrome b561: Molecular confirmation of a general five transmembrane structure and developmental regulation at the gastrula stage SO DNA AND CELL BIOLOGY LA English DT Article ID CHROMAFFIN GRANULE MEMBRANE; ELECTRON-TRANSFER; SEQUENCE; PROTEIN; ACID AB Cytochrome b561 transports electrons by a novel transmembrane vectoral pathway, Using the human cytochrome b561 cDNA probe, the Xenopus cytochrome b561 cDNA has been isolated and sequenced, A specific ATG was unambiguously identified because the Xenopus sequence has a stop codon 7 amino acids upstream from the initiation site ATG, The 741-bp open reading frame encodes a 247-amino-acid protein, The position of the initiating ATG site in Xenopus cytochrome b561 is consistent with the first ATG site in human and mouse proteins, and with the second of two ATG sites in the bovine protein, This result indicates that a five transmembrane domain model best represents the conformation of cytochrome b561 in membranes. Cytochrome b561 plays a fundamental role in the physiology of all neuroendocrine tissues, and the results presented here show that Xenopus cytochrome b561 mRNA is specific to neuroendocrine tissues and is developmentally regulated at the gastrula stage. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. RP Srivastava, M (reprint author), NIDDK,CELL BIOL & GENET LAB,NIH,BLDG 8,ROOM 405,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 1996 VL 15 IS 12 BP 1075 EP 1080 DI 10.1089/dna.1996.15.1075 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA WA177 UT WOS:A1996WA17700007 PM 8985121 ER PT J AU Wyatt, MK Philpot, RM Carver, G Lawton, MP Nikbakht, KN AF Wyatt, MK Philpot, RM Carver, G Lawton, MP Nikbakht, KN TI Structural characteristics of flavin-containing monooxygenase genes one and two (FMO1 and FM02) SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RABBIT LUNG; PRIMARY SEQUENCE; GUINEA-PIG; LIVER; CLONING; EXPRESSION; DISTINCT; OXIDASE; PURIFICATION; SPECIFICITY AB As a first step in understanding the regulation of the expression of flavin-containing monooxygenases (FMOs), we have isolated the FMO genes from the rabbit and characterized the gene for FMO1. Probes based on the 3', middle and 5' regions of the cDNAs encoding FMO1, FMO2, FMO3, and FMO5 were generated by polymerase chain reaction. A mixture of the 5' probes was used to screen a genomic library, and isolated clones were identified by hybridization with individual 5' probes. The complete gene for FMO1 was isolated as three overlapping clones and found to span similar to 40 kb. The gene contains eight introns, ranging in size from 1.4 to 10 kb and nine exons ranging in size from 73 to 747 bases. The gene for FMO1 seems to have multiple transcription start sites. A genomic clone containing a 5' segment of the FMO2 gene was isolated and found to contain intron 1, exon 1, and part of intron 2. The first intron of FMO2 is considerably smaller than that of FMO1 (0.3 vs, 3.8 kb), and its 3' junction is 52 bases to the 5' of the start codon, compared with 6 bases in the case of FMO1. In contrast, the 5' junction of intron 2 is the same distance from the start codon in both genes. The 5'-flanking regions of the FMO1 and FMO2 genes contain several putative glucocorticoid responsive elements. C1 NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 34 TC 9 Z9 9 U1 1 U2 1 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 DEC PY 1996 VL 24 IS 12 BP 1320 EP 1327 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VX885 UT WOS:A1996VX88500006 PM 8971137 ER PT J AU VallsSole, J Hallett, M Alvarez, R AF VallsSole, J Hallett, M Alvarez, R TI Postpulse effects on blink reflex responses SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE blink reflex; habituation; sensitization; prepulse inhibition; postpulse facilitation; startle ID RABBIT NICTITATING-MEMBRANE; EYEBLINK RESPONSE; HUMAN SUBJECT; STARTLE; HABITUATION; STIMULATION; SENSITIZATION; COMPONENTS; INHIBITION; STIMULUS AB The technique of paired stimulation is routinely used in many laboratories in the assessment of the excitability recovery curve of the blink reflex. Other effects, such as prepulse inhibition or classical conditioning, can also be investigated with repeated presentation of pairs of time-locked stimuli. Regularly repeated presentations of an unpleasant stimulus may give rise to a transient excitability enhancement in neural structures in the reflex circuit. We have investigated whether such a transient shift in excitability can be demonstrated before the actual stimulus is applied. In IO normal volunteers, we regularly alternated series of 5 trials containing an auditory tone of mild intensity with series of the same auditory tone followed by a relatively strong supraorbital nerve electrical stimulus. We calculated the habituation percentage of the orbicularis oculi responses to the auditory stimulus within a series and compared the results obtained in series containing the auditory tone alone with those from series containing the auditory tone followed by the electrical stimulus. Habituation was significantly less with paired stimulation than with the auditory tone alone, the mean area of the response to the 3rd trial in percentage of that to the first trial bring 34.0 +/- 16.4% for paired stimuli, and 20.3 +/- 14.1% for auditory stimulus alone (P = 0.008). This effect, induced by the presence of an impending electrical stimulus on the response to a preceding stimulus, is defined as a postpulse effect in contradistinction to the prepulse effects induced by a weak stimulus on the response to a subsequent startle-eliciting stimulus. When a paradigm with a stimulus pair is used in human subjects, the possibility of effects occurring in both temporal directions should be taken into account. Blink reflex responses to a given stimulus may exhibit excitability changes induced by a preceding or by an impending stimulus. Copyright (C) 1996 Elsevier Science Ireland Ltd. C1 NIH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. RP VallsSole, J (reprint author), UNIV BARCELONA,HOSP CLIN,DEPT MED,UNITAT EMG,SERV NEUROL,BARCELONA 08036,SPAIN. NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1996 VL 101 IS 6 BP 504 EP 510 PG 7 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA WE169 UT WOS:A1996WE16900006 PM 9020823 ER PT J AU Linnoila, M AF Linnoila, M TI Psychobiology of suicide SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Article C1 NIMH,SCI PROGRAM ALCOOLISME,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU DOIN EDITEURS PI PARIS PA 47 RUE SAINT-ANDRE-DES-ARTS, F-75006 PARIS, FRANCE SN 0013-7006 J9 ENCEPHALE JI Enceph.-Rev. Psychiatr. Clin. Biol. Ther. PD DEC PY 1996 VL 22 SI 4 BP 10 EP 14 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WJ896 UT WOS:A1996WJ89600003 PM 9138929 ER PT J AU Chaffin, CL Heimler, I Rawlins, RG Wimpee, BAB Sommer, C Hutz, RJ AF Chaffin, CL Heimler, I Rawlins, RG Wimpee, BAB Sommer, C Hutz, RJ TI Estrogen receptor and aromatic hydrocarbon receptor in the primate ovary SO ENDOCRINE LA English DT Article DE estrogen receptor; aromatic hydrocarbon receptor; ovary; corpus luteum; macaque; human ID MESSENGER-RIBONUCLEIC-ACID; MENSTRUAL-CYCLE; RHESUS-MONKEYS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; GRANULOSA-CELLS; CORPUS-LUTEUM; IMMUNOHISTOCHEMICAL LOCALIZATION; PROGESTERONE RECEPTORS; FOLLICULAR ATRESIA; RATS AB We have previously shown by immunocytochemistry and autoradiography the presence of estrogen receptors (ER) in rhesus monkey ovary. Intense chromogen staining showed specific binding for ER in nuclei of germinal epithelium and granulosa cells of antral follicles; and radiolabeled ligand bound specifically to functional corpora lutea (CL). Although it is accepted that the germinal epithelium of the primate ovary contains ER, some controversy still persists regarding the intraovarian localization of this molecule. In addition, no data exist that localize the aromatic hydrocarbon (dioxin) receptor (AHR), which is known to modulate ER, to the primate ovary. In the present study, we show the presence of ER using Western blot analysis, and ER capable of binding DNA within intraovarian compartments in two species of the genus Macaca (rhesus macaque, Macaca mulatta and stumptail macaque, Macaca arctoides); extend these findings to human ovarian granulosa cells (CC) using Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and gel mobility-shift analysis; and localize the AHR to intraovarian compartments of the macaque ovary by Western blots and gel-shift assays. These experiments strongly suggest that estrogens can exert effects on follicle development directly at the ovary, and provide the first direct evidence that AHR-mediated toxicity may be manifested at the ovary to induce possible antifertility effects. C1 UNIV WISCONSIN,DEPT BIOL SCI,MILWAUKEE,WI 53211. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT OB GYN,CHICAGO,IL 60612. UNIV WISCONSIN,NIEHS,BIOMED SCI CTR,MILWAUKEE,WI 53201. OREGON REG PRIMATE RES CTR,DIV REPROD SCI,BEAVERTON,OR 97006. NR 37 TC 25 Z9 25 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0969-711X J9 ENDOCRINE JI Endocrine PD DEC PY 1996 VL 5 IS 3 BP 315 EP 321 DI 10.1007/BF02739065 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WD563 UT WOS:A1996WD56300011 PM 21153083 ER PT J AU Friedman, TC Mastorakos, G Newman, TD Mullen, NM Horton, EG Costello, R Papadopoulos, NM Chrousos, GP AF Friedman, TC Mastorakos, G Newman, TD Mullen, NM Horton, EG Costello, R Papadopoulos, NM Chrousos, GP TI Carbohydrate and lipid metabolism in endogenous hypercortisolism: Shared features with metabolic syndrome X and NIDDM SO ENDOCRINE JOURNAL LA English DT Article DE Cushing's; diabetes; insulin; syndrome X; Lp(a) ID BODY-FAT DISTRIBUTION; DEPENDENT DIABETES-MELLITUS; INSULIN RESISTANCE; CUSHINGS-SYNDROME; RHEUMATIC DISEASES; GLUCAGON-SECRETION; RAT ISLETS; CORTISOL; PLASMA; THERAPY AB Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1c over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P<0.0005), UFC and OGTT glucose area under the curve (AUC) (P<0.01), and UFC and HbA1c (P<0.005). UFC levels were negatively correlated (P<0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia. Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension. However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect ''toxic'' effect on the beta-cell. C1 NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIH, DEPT CLIN PATHOL, CTR CLIN, BETHESDA, MD 20892 USA. RP Friedman, TC (reprint author), UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR,SCH MED,DEPT MED, DIV ENDOCRINOL, B-131, LOS ANGELES, CA 90048 USA. NR 57 TC 86 Z9 88 U1 1 U2 2 PU JAPAN ENDOCRINE SOCIETY PI TOKYO PA C/O DEPT VETERINARY PHYSIOL, VET MED SCI, UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO 113, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD DEC PY 1996 VL 43 IS 6 BP 645 EP 655 DI 10.1507/endocrj.43.645 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ906 UT WOS:A1996VZ90600007 PM 9075604 ER PT J AU BeckPeccoz, P BruckerDavis, F Persani, L Smallridge, RC Weintraub, BD AF BeckPeccoz, P BruckerDavis, F Persani, L Smallridge, RC Weintraub, BD TI Thyrotropin-secreting pituitary tumors SO ENDOCRINE REVIEWS LA English DT Review ID THYROID-STIMULATING HORMONE; ACTING SOMATOSTATIN ANALOG; MESSENGER-RIBONUCLEIC-ACID; PRIMARY HYPO-THYROIDISM; LECTIN AFFINITY-CHROMATOGRAPHY; MCCUNE-ALBRIGHT SYNDROME; IN-SITU HYBRIDIZATION; PRIMARY HYPOTHYROIDISM; GROWTH-HORMONE; INAPPROPRIATE SECRETION C1 UNIV MILAN, OSPED MAGGIORE, IRCCS, INST ENDOCRINE SCI, MILAN, ITALY. IRCCS, CTR AUXOL ITALIANO, MILAN, ITALY. NIDDK, MOL & CELLULAR ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. MAYO CLIN JACKSONVILLE, DIV ENDOCRINOL, JACKSONVILLE, FL 32224 USA. RI Persani, Luca/B-6543-2008; OI Persani, Luca/0000-0003-2068-9581 NR 377 TC 265 Z9 285 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 1996 VL 17 IS 6 BP 610 EP 638 DI 10.1210/er.17.6.610 PG 29 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VX873 UT WOS:A1996VX87300002 PM 8969971 ER PT J AU Strott, CA AF Strott, CA TI Steroid sulfotransferases SO ENDOCRINE REVIEWS LA English DT Review ID LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; ADENOSINE 3'-PHOSPHATE 5'-PHOSPHOSULFATE; HEPATIC HYDROXYSTEROID SULFOTRANSFERASE; ENDOMETRIAL ESTROGEN SULFOTRANSFERASE; STEREOSELECTIVE SULFATE CONJUGATION; DNA-BINDING PROTEINS; MAMMARY-CANCER CELLS; AMINO-ACID-SEQUENCE; HUMAN-FETAL LIVER; RAT-LIVER RP Strott, CA (reprint author), NICHHD,STEROID REGULAT SECT,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892, USA. NR 221 TC 140 Z9 140 U1 2 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 1996 VL 17 IS 6 BP 670 EP 697 DI 10.1210/er.17.6.670 PG 28 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VX873 UT WOS:A1996VX87300004 PM 8969973 ER PT J AU Zeiger, MA Saji, M Caturegli, P Westra, WH Kohn, LD Levine, MA AF Zeiger, MA Saji, M Caturegli, P Westra, WH Kohn, LD Levine, MA TI Transformation of rat thyroid follicular cells stably transfected with cholera toxin A1 fragment SO ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-I; THYROTROPIN RECEPTOR; ALPHA-SUBUNIT; G-PROTEIN; SOMATIC MUTATIONS; ADENYLATE-CYCLASE; ACTIVATION; TUMORS; STIMULATION; ADENOMAS AB Activating mutations of the alpha subunit of the G protein G(s) (G(s) alpha) have been identified in thyroid adenomas and well-differentiated thyroid carcinomas. To examine the role of activating mutations of G(s) alpha in thyroid neoplasia, we transfected rat follicular thyroid (FRTL-5) cells with a transgene in which the cholera toxin A1 subunit (CTA1) is expressed under the control of the rat thyroglobulin gene promoter (TG). This transgene recapitulates effects of the activating mutation of G(s) alpha by its ability to ADP-ribosylate and thereby inhibit GTPase activity of endogenous G(s) alpha molecules. To assess the effect of G(s) alpha activation on cell growth, TGCTA1, or control, pM AM neotransfected FRTL-5 cells (10(4)-10(6)) were injected sc into nude mice. TGCTA1-transfected FRTL-5 cells grow in nude mice, whereas control cells do not. Tumor histology revealed increased mitotic activity, infiltration of skeletal muscle, perineural invasion, and plugging of lymphatic spaces. In addition, nude mice injected with TGCTA1 transfected cells or xenografted with the tumors developed metastases to lung. These results indicate that activation of G(s) alpha and constitutive production of cAMP in FRTL-5 cells can result in TSH-independent cellular proliferation and neoplastic transformation. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT SURG, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA. NIDDKD, NIH, BETHESDA, MD 20892 USA. RI Saji, Motoyasu/E-4007-2011; OI Levine, Michael/0000-0003-0036-7809 NR 47 TC 13 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1996 VL 137 IS 12 BP 5392 EP 5399 DI 10.1210/en.137.12.5392 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU351 UT WOS:A1996VU35100030 PM 8940362 ER PT J AU Cool, DR Louie, DY Loh, YP AF Cool, DR Louie, DY Loh, YP TI Yeast aspartic protease 3 is sorted to secretory granules and activated to process proopiomelanocortin in PC12 cells SO ENDOCRINOLOGY LA English DT Article ID OPIOMELANOCORTIN-CONVERTING ENZYME; PITUITARY INTERMEDIATE LOBE; PRO-OPIOMELANOCORTIN; HORMONE BIOSYNTHESIS; ATT-20 CELLS; PRECURSOR; VESICLES; ENDOPROTEASES; PURIFICATION; PROTEOLYSIS AB The subcellular localization and functionality of transfected yeast aspartic protease 3 (YAP3p) in a mammalian cell line were investigated. The complementary DNAs encoding the prohormone-processing enzyme (YAP3p) and a prohormone, bovine POMC, were cotransfected into PC12 (rat pheochromocytoma) cells. Immunocytochemical analysis of the cells using a YAP3p antibody showed a perinuclear punctate distribution of YAP3p in the cell body as well as immunostaining in the tips of the neurites. This pattern of immunostaining indicates localization of YAP3p in secretory granules. Analysis of the processing of POMC showed that in cells transfected with the POMC complementary DNA alone, only POMC was found, indicating a lack of processing of the prohormone. However, in cells coexpressing YAP3p, the POMC was completely processed to yield ACTH-(1-39) and ACTH-(1-14), consistent with the specificity of YAP3p found in vitro. Pulse-chase studies showed that POMC was processed after 20 min of chase, suggesting that processing occurred in the late Golgi network and continued in the Secretory granules. Western blot analysis determined that YAP3p was secreted from the cells in a regulated manner. This study provides the first demonstration that a yeast prohormone-processing enzyme (YAP3p) of the aspartic protease class can be sorted correctly to secretory granules and activated to process a prohormone (POMC) in a highly efficient manner in mammalian cells. C1 NICHHD, DEV NEUROBIOL LAB, CELLULAR NEUROBIOL SECT, NIH, BETHESDA, MD 20892 USA. NR 43 TC 11 Z9 11 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 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1996 VL 137 IS 12 BP 5441 EP 5446 DI 10.1210/en.137.12.5441 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU351 UT WOS:A1996VU35100037 PM 8940369 ER PT J AU Mores, N Krsmanovic, LZ Catt, KJ AF Mores, N Krsmanovic, LZ Catt, KJ TI Activation of LH receptors expressed in GnRH neurons stimulates cyclic AMP production and inhibits pulsatile neuropeptide release SO ENDOCRINOLOGY LA English DT Article ID G-PROTEINS; GONADOTROPIN; CELLS AB The GT1-7 cell line of immortalized GnRH neurons has been shown to express receptors for GnRH, LH, and prolactin, as well as a variety of other hormones and transmitters. Treatment of GT1-7 cells with hCG caused a dose-dependent increase in cAMP production, with a rapid increase during the first 15 min and a subsequent decrease that was prevented by pre-treatment with pertussis toxin. Furthermore, the stimulatory effect of cholera toxin on cAMP production was inhibited by hCG in a dose-dependent manner. These data indicate that the LH receptors expressed in GT1-7 cells are coupled to adenylyl cyclase both stimulatory (G(s)) and inhibitory (G(i)) proteins. In perifused cell cultures, treatment with forskolin and 8-bromo cAMP increased the amplitude of spontaneous GnRH release. However, treatment with nanomolar concentrations of hCG abolished pulsatile GnRH release from both GT1-7 cells and rat hypothalamic cells. The similarity of hCG action on pulsatile GnRH release to that of extracellular Ca2+ depletion and calcium channel antagonists, and its partial resistance to potassium-induced depolarization, suggest that it results from inhibition of plasma-membrane ion channel activity. It is probable that the inhibitory action of hCG on pulsatile GnRH release is responsible for initiation of the suppression of pituitary LH secretion during pregnancy. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, NIH, BETHESDA, MD 20892 USA. OI MORES, Nadia/0000-0002-4197-0914 NR 22 TC 31 Z9 31 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 DEC PY 1996 VL 137 IS 12 BP 5731 EP 5734 DI 10.1210/en.137.12.5731 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU351 UT WOS:A1996VU35100078 PM 8940408 ER PT J AU Webster, EL Lewis, DB Torpy, DJ Zachman, EK Rice, KC Chrousos, GP AF Webster, EL Lewis, DB Torpy, DJ Zachman, EK Rice, KC Chrousos, GP TI In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: Suppression of pituitary ACTH release and peripheral inflammation SO ENDOCRINOLOGY LA English DT Article ID RAT-BRAIN; IN-VITRO; IDENTIFICATION; CLONING; HEART; EXPRESSION; SITES AB Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. CRH receptors (CRH-R1, R2 alpha, R2 beta) exhibit a specific tissue distribution. Antalarmin, a novel pyrrolopyrimidine compound, displaced I-125-oCRH binding in rat pituitary, frontal cortex and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmin (20 mg/kg body wt.) significantly inhibited CRH-stimulated ACTH release and carageenin-induced subcutaneous inflammation in rats. Antalarmin, or its analogs, hold therapeutic promise in disorders with putative CRH hypersecretion, such as melancholic depression and inflammatory disorders. C1 NIDDK, MED CHEM BRANCH, NIH, BETHESDA, MD 20892 USA. RP Webster, EL (reprint author), NICHHD, PEDIAT ENDOCRINOL SECT, DEB, BETHESDA, MD 20892 USA. NR 24 TC 242 Z9 247 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1996 VL 137 IS 12 BP 5747 EP 5750 DI 10.1210/en.137.12.5747 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VU351 UT WOS:A1996VU35100082 PM 8940412 ER PT J AU Gulson, BL Pisaniello, D McMichael, AJ Mizon, KJ Korsch, MJ Luke, C Ashbolt, R Pederson, DG Vimpani, G Mahaffey, KR AF Gulson, BL Pisaniello, D McMichael, AJ Mizon, KJ Korsch, MJ Luke, C Ashbolt, R Pederson, DG Vimpani, G Mahaffey, KR TI Stable lead isotope profiles in smelter and general urban communities: A comparison of environmental and blood measures SO ENVIRONMENTAL GEOCHEMISTRY AND HEALTH LA English DT Article DE lead; blood; environmental samples; isotopes ID CHILDREN; ABSORPTION; IDENTIFICATION; EXPOSURE AB High-precision lead isotope ratios and lead concentrations have been compared statistically and graphically in women of child-bearing age (n = 77) from two smelter communities and one general urban community to evaluate the relative contributions to blood lead of tissue lead stores and lead from the contemporaneous environment (soil, floor dust, indoor airborne dust, water, food). Blood lead (PbB) contents were generally low (e.g. <10 mu g dL(-1)). Statistically significant isotopic differences in blood and environmental samples were observed between the three cities although isotopic differences in blood for individual subjects living in close proximity (similar to 200 m radius) was as large as the differences within a city. No single environmental measure dominated the biological isotope profile and in many cases the low levels of blood lead meant that their isotopic profiles could be easily perturbed by relatively small changes of environmental exposure. Apportioning of sources using lead isotopes is possibly not feasible, nor cost effective, when blood lead levels are <5 mu g dL(-1). Interpretations based on statistical analyses of city-wide data do not give the same conclusions as when the houses are considered individually. Aggregating data from multiple subjects in a study such as this obscures potentially useful information. Most of the measures employed in this study, and many other similar studies, are markers of only short-to-medium integration of lead exposure. Serial sampling of blood and longer sampling times, especially for household variables, should provide more meaningful information. C1 CSIRO,DEM,MINERALS RES LAB,N RYDE,NSW 2113,AUSTRALIA. HLTH COMMISS,ADELAIDE,SA,AUSTRALIA. UNIV TASMANIA,MENZIES CTR,HOBART,TAS,AUSTRALIA. UNIV CANBERRA,CANBERRA,ACT,AUSTRALIA. CHILD FAMILY & ADOLESCENT HLTH,NEWCASTLE,NSW,AUSTRALIA. NIEHS,RES TRIANGLE PK,NC 27709. UNIV ADELAIDE,DEPT COMMUNITY MED,ADELAIDE,SA,AUSTRALIA. NR 26 TC 33 Z9 33 U1 1 U2 5 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0269-4042 J9 ENVIRON GEOCHEM HLTH JI Environ. Geochem. Health PD DEC PY 1996 VL 18 IS 4 BP 147 EP 163 DI 10.1007/BF01771238 PG 17 WC Engineering, Environmental; Environmental Sciences; Public, Environmental & Occupational Health; Water Resources SC Engineering; Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Water Resources GA WB639 UT WOS:A1996WB63900003 PM 24194410 ER PT J AU Huff, J AF Huff, J TI alpha 2 mu-globulin nephropathy, posed mechanisms, and white ravens - Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID ALPHA-2U-GLOBULIN NEPHROPATHY; CHEMICAL CARCINOGENESIS; RENAL CARCINOGENESIS; CELL-PROLIFERATION; RATS; TOXICITY; CANCER; EXPOSURE; ABSENCE; TUMORS RP Huff, J (reprint author), NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC, USA. NR 34 TC 19 Z9 19 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 IS 12 BP 1264 EP 1267 DI 10.2307/3432949 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WE308 UT WOS:A1996WE30800003 ER PT J AU Shelby, MD Newbold, RR Tully, DB Chae, K Davis, VL AF Shelby, MD Newbold, RR Tully, DB Chae, K Davis, VL TI Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE competitive binding; endocrine disruptors; estrogen receptor; transfection; uterotropic assay ID RECEPTOR; CELLS AB Because of rampant concern that estrogenic chemicals in the environment may be adversely affecting the health of humans and wildlife, reliable methods for detecting and characterizing estrogenic chemicals are needed. It is important that general agreement be reached on which tests to use and that these tests then be applied to the testing of both man-made and naturally occurring chemicals. As a step toward developing a comprehensive approach to screening chemicals for estrogenic activity, three assays for detecting estrogenicity were conducted on 10 chemicals with known or suspected estrogenic activity. The assays were 1) competitive binding with the mouse uterine estrogen receptor, 2) transcriptional activation in HeLa cells transfected with plasmids containing an estrogen receptor and a response element, and 3) the uterotropic assay in mice. The chemicals studied were 17 beta-estradiol, diethylstilbestrol, tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxychlor metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), endosulfan, nonylphenol, o,p'-DDT, and kepone. These studies were conducted to assess the utility of this three-assay combination in the routine screening of chemicals, or combinations of chemicals, for estrogenic activity. Results were consistent among the three assays with respect to what is known about the estrogenic activities of the chemicals tested and their requirements for metabolic activation. By providing information on three levels of hormonal activity (receptor binding, transcriptional activation, and an in vivo effect in an estrogen-responsive tissue), an informative profile of estrogenic activity is obtained with a reasonable investment of resources. C1 NIEHS,FUNCT TOXICOL GRP,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,ENVIRONM BIOL PROGRAM,RES TRIANGLE PK,NC 27709. RP Shelby, MD (reprint author), NIEHS,REPROD TOXICOL GRP,POB 12233,MD A2-03,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 350 Z9 370 U1 7 U2 27 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 IS 12 BP 1296 EP 1300 DI 10.2307/3432965 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WE308 UT WOS:A1996WE30800023 PM 9118870 ER PT J AU Zhang, LP Rothman, N Wang, YX Hayes, RB Bechtold, W Venkatesh, P Yin, SN Wang, YZ Dosemeci, M Li, GL Lu, W Smith, MT AF Zhang, LP Rothman, N Wang, YX Hayes, RB Bechtold, W Venkatesh, P Yin, SN Wang, YZ Dosemeci, M Li, GL Lu, W Smith, MT TI Interphase cytogenetics of workers exposed to benzene SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Conference on the Toxicity, Carcinogenesis, and Epidemiology of Benzene (Benzene 95) CY JUN 17-20, 1995 CL PISCATAWAY, NJ SP Rutgers Univ, Off Continuing Profess Educ, State Univ New Jersey, Univ Med Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol DE benzene; aneuploidy; hyperdiploidy; chromosome aberrations; leukemia ID FLUORESCENCE INSITU HYBRIDIZATION; IN-SITU HYBRIDIZATION; HUMAN-LYMPHOCYTES; CHROMOSOMAL-ABERRATIONS; DNA PROBES; 1,2,4-BENZENETRIOL; MICRONUCLEI; METABOLITES; ANEUPLOIDY; DAMAGE AB Fluorescence in situ hybridization (FISH) is a powerful new technique that allows numerical chromosome aberrations (aneuploidy) to be detected in interphase cells. In previous studies, FISH has been used to demonstrate that the benzene metabolites hydroquinone and 1,2,4-benzenetriol induce aneuploidy of chromosomes 7 and 9 in cultures of human cells. In the present study, we used an interphase FISH procedure to perform cytogenetic analyses on the blood cells of 43 workers exposed to benzene (median=31 ppm. Bhr time-weighted average) and 44 matched controls from Shanghai, China. High benzene exposure (>31 ppm, n=22) increased the hyperdiploid frequency of chromosome 9 (p<0.01), but lower exposure (less than or equal to 31 ppm, n=21) did not. Trisomy 9 was the major form of benzene-induced hyperdiploidy. The level of hyperdiploidy in exposed workers correlated with their urinary phenol level (r=0.58, p<0.0001), a measure of internal benzene dose. A significant correlation was also found between hyperdiploidy and decreased absolute lymphocyte count, an indicator of benzene hematotoxicity, in the exposed group (r=-0.44, p=0.003) but not in controls (r=-0.09, p=0.58). These results show that high benzene exposure induces aneuploidy of chromosome 9 in nondiseased individuals, with trisomy being the most prevalent form. They further highlight the usefulness of interphase cytogenetics and FISH for the rapid and sensitive detection of aneuploidy in exposed human populations. C1 NATL CANC INST,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD. LOVELACE INHALAT TOXICOL RES INST,ALBUQUERQUE,NM. CHINESE ACAD PREVENT MED,BEIJING,PEOPLES R CHINA. SHANGHAI HYG & ANTIEPIDEM CTR,DEPT OCCUPAT HLTH,SHANGHAI,PEOPLES R CHINA. RP Zhang, LP (reprint author), UNIV CALIF BERKELEY,SCH PUBL HLTH,140 WARREN HALL,BERKELEY,CA 94720, USA. FU NIEHS NIH HHS [R01 ES06721] NR 35 TC 53 Z9 66 U1 1 U2 6 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 SU 6 BP 1325 EP 1329 DI 10.2307/3433184 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WC466 UT WOS:A1996WC46600035 PM 9118914 ER PT J AU Yin, SN Hayes, RB Linet, MS Li, GL Dosemeci, M Travis, LB Zhang, ZN Li, DG Chow, WH Wacholder, S Blot, WJ Wang, YZ Jiang, ZL Dai, TR Zhang, WY Chao, XY Ye, PZ Kou, QR Chang, XC Lin, XF Meng, JF Ding, CY Zho, JS AF Yin, SN Hayes, RB Linet, MS Li, GL Dosemeci, M Travis, LB Zhang, ZN Li, DG Chow, WH Wacholder, S Blot, WJ Wang, YZ Jiang, ZL Dai, TR Zhang, WY Chao, XY Ye, PZ Kou, QR Chang, XC Lin, XF Meng, JF Ding, CY Zho, JS TI An expanded cohort study of cancer among benzene-exposed workers in China SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Conference on the Toxicity, Carcinogenesis, and Epidemiology of Benzene (Benzene 95) CY JUN 17-20, 1995 CL PISCATAWAY, NJ SP Rutgers Univ, Off Continuing Profess Educ, State Univ New Jersey, Univ Med Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol DE benzene; leukemia; malignant lymphoma; lung cancer; aplastic anemia ID RETROSPECTIVE COHORT; LEUKEMIA; MORTALITY AB An expanded cohort study of 74,828 benzene-exposed and 35,805 unexposed workers were followed during 1972 to 1987, based on a previous study in 12 cities in China. A small increase was observed in total cancer mortality among benzene-exposed compared with unexposed workers (relative risk [RR]=1.2). Statistically significant excesses were noted for leukemia (RR=2.3), malignant lymphoma (RR=4.5), and lung cancer (RR=1.4). When risks were evaluated by leukemia subtype, only acute myelogenous leukemia was significantly elevated (RR=3.1), although nonsignificant excesses were also noted for chronic myelogenous leukemia (RR=2.6) and acute lymphocytic leukemia (RR=2.3). A significant excess was also found for aplastic anemia. C1 NATL CANC INST, BETHESDA, MD USA. RP Yin, SN (reprint author), CHINESE ACAD PREVENT MED, INST OCCUPAT MED, 29 NAN WEI RD, BEIJING 100950, PEOPLES R CHINA. NR 18 TC 84 Z9 86 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 SU 6 BP 1339 EP 1341 DI 10.2307/3433187 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WC466 UT WOS:A1996WC46600038 PM 9118917 ER PT J AU Dosemeci, M Yin, SN Linet, M Wacholder, S Rothman, N Li, GL Chow, WH Wang, YZ Jiang, ZL Dai, TR Zhang, WU Chao, XJ Ye, PZ Kou, QR Fan, YH Zhang, XC Lin, XF Meng, JF Zho, JS Blot, WJ Hayes, RB AF Dosemeci, M Yin, SN Linet, M Wacholder, S Rothman, N Li, GL Chow, WH Wang, YZ Jiang, ZL Dai, TR Zhang, WU Chao, XJ Ye, PZ Kou, QR Fan, YH Zhang, XC Lin, XF Meng, JF Zho, JS Blot, WJ Hayes, RB TI Indirect validation of benzene exposure assessment by association with benzene poisoning SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Conference on the Toxicity, Carcinogenesis, and Epidemiology of Benzene (Benzene 95) CY JUN 17-20, 1995 CL PISCATAWAY, NJ SP Rutgers Univ, Off Continuing Profess Educ, State Univ New Jersey, Univ Med Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol DE validation; exposure estimates; benzene exposure; exposure assessment method; reconstruction of historical exposure ID OCCUPATIONAL EXPOSURE; VALIDITY; COHORT; CHINA; INFORMATION; AGREEMENT; CANCER AB We present a validation study of a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work unit/job title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures were observed for the rubber industry (30.7 ppm) and for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning and benzene exposure was evaluated to validate the assessment method that we used in the cohort study. Our confidence in the assessment method is supported by the observation of a strong positive trend between benzene poisoning and various measures, especially recent intensity of exposure to benzene. C1 CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING 100050,PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT,SHANGHAI,PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS,SHENYANG,PEOPLES R CHINA. NCI,DIV EPIDEMIOL & GENET,BETHESDA,MD. INT EPIDEMIOL INST,ROCKVILLE,MD. RI Zhang, Xi-Cheng/G-1306-2016 OI Zhang, Xi-Cheng/0000-0003-3721-1357 NR 23 TC 27 Z9 32 U1 1 U2 2 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 SU 6 BP 1343 EP 1347 DI 10.2307/3433188 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WC466 UT WOS:A1996WC46600039 PM 9118918 ER PT J AU Hayes, RB Yin, SN Dosemeci, M Li, GL Wacholder, S Chow, WH Rothman, N Wang, YZ Dai, TR Chao, XJ Jiang, ZL Ye, PZ Zhao, HB Kou, QR Zhang, WY Meng, JF Zho, JS Lin, XF Ding, CY Li, CY Zhang, ZN Li, DG Travis, LB Blot, WJ Linet, MS AF Hayes, RB Yin, SN Dosemeci, M Li, GL Wacholder, S Chow, WH Rothman, N Wang, YZ Dai, TR Chao, XJ Jiang, ZL Ye, PZ Zhao, HB Kou, QR Zhang, WY Meng, JF Zho, JS Lin, XF Ding, CY Li, CY Zhang, ZN Li, DG Travis, LB Blot, WJ Linet, MS TI Mortality among benzene-exposed workers in China SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Conference on the Toxicity, Carcinogenesis, and Epidemiology of Benzene (Benzene 95) CY JUN 17-20, 1995 CL PISCATAWAY, NJ SP Rutgers Univ, Off Continuing Profess Educ, State Univ New Jersey, Univ Med Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol DE benzene; cancer; lymphatic; hematopoietic; lung cancer; epidemiology ID RETROSPECTIVE COHORT; LEUKEMIA AB A large cohort of 74,828 benzene-exposed and 35,805 nonexposed workers employed between 1972 and 1987 in 12 cities in China was followed to determine mortality from all causes. Benzene-exposed study subjects were employed in a Variety of occupations including coating applications, and rubber, chemical, and shoe production. Mortality was slightly increased among workers with greater cumulative exposure to benzene (p(trend) < 0.05), but this excess was largely due to cancer deaths (p(trend) < 0.01). Deaths due to lymphatic and hematopoietic malignancies (p(trend) = 0.01) and lung cancer (p(trend) = 0.01) increased with increasing cumulative exposure to benzene. investigations continue to relate benzene exposure to specific lymphatic and hematopoietic malignancies and other causes of death. C1 CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING 100050, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, SHANGHAI, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHENGDU, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHONGQING, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, TIANJIN, PEOPLES R CHINA. INST LAB HLTH & OCCUPAT DIS, HEILONGJIANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, LUOYANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SHENYANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SICHUAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JIANGXI, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, NANCHANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, GUANGZHOU, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JINZHOU, PEOPLES R CHINA. MAYO CLIN, HEMATOPATHOL SECT, ROCHESTER, MN USA. CHINESE ACAD MED SCI, DIV HEMATOL, PEKING UNION MED HOSP, BEIJING 100037, PEOPLES R CHINA. RP Hayes, RB (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, NIH, 6130 EXECUT BLVD, MSC 7368, BETHESDA, MD 20892 USA. NR 25 TC 53 Z9 53 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 SU 6 BP 1349 EP 1352 DI 10.2307/3433189 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WC466 UT WOS:A1996WC46600040 PM 9118919 ER PT J AU Linet, MS Yin, SN Travis, LB Li, CY Zhang, ZN Li, DG Rothman, N Li, GL Chow, WH Donaldson, J Dosemeci, M Wacholder, S Blot, WJ Hayes, RB Wang, YZ Dai, TR Chao, XJ Qing, C Jiang, ZL Zhang, WU Ye, PZ Kou, QR Fan, YH Zhang, XC Lin, XF Meng, JF Zho, JS AF Linet, MS Yin, SN Travis, LB Li, CY Zhang, ZN Li, DG Rothman, N Li, GL Chow, WH Donaldson, J Dosemeci, M Wacholder, S Blot, WJ Hayes, RB Wang, YZ Dai, TR Chao, XJ Qing, C Jiang, ZL Zhang, WU Ye, PZ Kou, QR Fan, YH Zhang, XC Lin, XF Meng, JF Zho, JS TI Clinical features of hematopoietic malignancies and related disorders among benzene-exposed workers in China SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Conference on the Toxicity, Carcinogenesis, and Epidemiology of Benzene (Benzene 95) CY JUN 17-20, 1995 CL PISCATAWAY, NJ SP Rutgers Univ, Off Continuing Profess Educ, State Univ New Jersey, Univ Med Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol DE hematopoietic malignancies; benzene; leukemia; acute myeloid leukemia; chronic myeloid leukemia; non-Hodgkin's lymphoma; aplastic anemia; myelodysplastic syndromes; dyspoiesis ID ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; CAUSE-SPECIFIC MORTALITY; RUBBER WORKERS; CANCER MORTALITY; CHEMICAL WORKERS; OCCUPATIONAL EXPOSURE; RISK ASSESSMENT; MYELODYSPLASTIC SYNDROMES; GENERAL MORTALITY AB Previous occupational cohort studies of benzene-exposed workers have for the most part used only death certificates to validate diagnoses of workers developing leukemia and other hematopoietic and lymphoproliferative malignancies and related disorders (HLD). In a follow-up study of 74,828 benzene-exposed workers and a comparison group of 35,805 nonexposed workers from 12 cities in China, we sought to characterize clinicopathologically and to confirm diagnoses of ail cases of HLD. Using medical records, laboratory hematology results, and histopathology, U.S. and Chinese expert hematopathologists, blinded to exposure status, carried out a detailed review using standardized evaluation forms. Key among the findings were a notable diversity of malignant and nonneoplastic hematopoietic and lymphoproliferative disorders, documentation of excess myelodysplastic syndromes among benzene workers, and widespread dyspoiesis involving all hematopoietic cell lines. As sophisticated clinicopathologic characterization and corresponding classification schemes for HLD become increasingly widespread, it is recommended that future epidemiologic investigations of benzene workers incorporate similarly detailed morphologic evaluation. In extending follow-up of this cohort of young workers, we will continue to use ail available clinical, laboratory hematology, and pathology data as well as cytogenetic and biochemical markers to characterize various HLD outcomes. These careful surveillance mechanisms should also provide additional insight into carcinogenic mechanisms of benzene and allow comparison of the molecular pathogenesis of HLD induced by benzene versus chemotherapy, radiation, or other exposure. C1 CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING 100050, PEOPLES R CHINA. MAYO CLIN, HEMATOPATHOL SECT, ROCHESTER, MN USA. CHINESE ACAD MED SCI, BEIJING UNIV,PEKING UNION MED COLL HOSP,SCH MED, DIV HEMATOL, BEIJING, PEOPLES R CHINA. RP Linet, MS (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, 6130 EXECUT BLVD, MSC 7368, BETHESDA, MD 20892 USA. NR 115 TC 30 Z9 32 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 SU 6 BP 1353 EP 1364 DI 10.2307/3433190 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WC466 UT WOS:A1996WC46600041 PM 9118920 ER PT J AU Rothman, N Smith, MT Hayes, RB Li, GL Irons, RD Dosemeci, M Haas, R Stillman, WS Linet, M Xi, LQ Bechtold, WE Wiemels, J Campleman, S Zhang, LP Quintana, PJE TitenkoHolland, N Wang, YZ Lu, W Kolachana, P Meyer, KB Yin, SN AF Rothman, N Smith, MT Hayes, RB Li, GL Irons, RD Dosemeci, M Haas, R Stillman, WS Linet, M Xi, LQ Bechtold, WE Wiemels, J Campleman, S Zhang, LP Quintana, PJE TitenkoHolland, N Wang, YZ Lu, W Kolachana, P Meyer, KB Yin, SN TI An epidemiologic study of early biologic effects of benzene in Chinese workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Conference on the Toxicity, Carcinogenesis, and Epidemiology of Benzene (Benzene 95) CY JUN 17-20, 1995 CL PISCATAWAY, NJ SP Rutgers Univ, Off Continuing Profess Educ, State Univ New Jersey, Univ Med Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol DE benzene; hydroquinone; muconic acid; hematotoxicity; cytokines; biomarkers; molecular epidemiology; somatic cell mutations; leukemogenesis ID COLONY-STIMULATING FACTOR; GLYCOPHORIN-A LOCUS; INHALED BENZENE; MYELODYSPLASTIC SYNDROMES; EXPOSURE; METABOLITES; MUTATIONS; INVITRO; GROWTH; CELLS AB Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average, 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cell levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levers. All peripheral blood cell levels (i.e., total while blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to Values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans. C1 UNIV CALIF BERKELEY, SCH PUBL HLTH, BERKELEY, CA USA. CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING 100050, PEOPLES R CHINA. UNIV COLORADO, HLTH SCI CTR, MOL TOXICOL & ENVIRONM HLTH SCI PROGRAM, DENVER, CO USA. CALIF DEPT TOX SUBST CONTROL, HAZARDOUS MAT LAB, BERKELEY, CA USA. INHALAT TOXICOL RES INST, ALBUQUERQUE, NM 87185 USA. SAN DIEGO STATE UNIV, GRAD SCH PUBL HLTH, SAN DIEGO, CA 92182 USA. SHANGHAI HYG & ANTIEPIDEM CTR, DEPT OCCUPAT HLTH, SHANGHAI, PEOPLES R CHINA. RP Rothman, N (reprint author), NCI, DIV EPIDEMIOL & GENET, BETHESDA, MD 20892 USA. FU NIEHS NIH HHS [P30ES01896, P42ES04705] NR 40 TC 50 Z9 52 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1996 VL 104 SU 6 BP 1365 EP 1370 DI 10.2307/3433191 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WC466 UT WOS:A1996WC46600042 PM 9118921 ER PT J AU Kelloff, GJ Hawk, ET Crowell, JA Boone, CW Steele, VE Lubet, RA Sigman, CC AF Kelloff, GJ Hawk, ET Crowell, JA Boone, CW Steele, VE Lubet, RA Sigman, CC TI Perspectives on chemoprevention agent selection and short-term clinical prevention trials SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; PROSTATE-CANCER; REDUCED RISK; TAMOXIFEN; SULINDAC; ASPIRIN; INHIBITOR; TUMORS; RATS C1 CCS ASSOCIATES,MT VIEW,CA 94043. RP Kelloff, GJ (reprint author), NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,NATL INST HLTH,EXECUT PLAZA N,SUITE 201,BETHESDA,MD 20892, USA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD DEC PY 1996 VL 5 SU 2 BP 79 EP 85 DI 10.1097/00008469-199612002-00012 PG 7 WC Oncology SC Oncology GA WM763 UT WOS:A1996WM76300012 PM 9061299 ER PT J AU Morita, YS Jung, G Hammer, JA Fukui, Y AF Morita, YS Jung, G Hammer, JA Fukui, Y TI Localization of Dictyostelium myoB and myoD to filopodia and cell-cell contact sites using isoform-specific antibodies SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE Dictyostelium; myosin I; filopodium; cell-cell contact; ratio imaging ID ACTIN-BINDING SITE; HEAVY-CHAIN ISOFORM; MAMMALIAN MYOSIN-I; ACANTHAMOEBA-CASTELLANII; INTRACELLULAR-LOCALIZATION; VEGETATIVE AMEBAS; DISCOIDEUM; RICH; IDENTIFICATION; SEQUENCE AB To date, five myosin I heavy chain genes (myoA-E) have been sequenced in Dictyostelium. Among them, myoB, myoC and myoD possess tail domains that contain a putative membrane-binding domain, a nucleotide-insensitive actin-binding site, and an src homology (SN)-3 domain. In this study, we have determined the intracellular localizations of myoB and myoD by immunofluorescence using isoform-specific antibodies raised against bacterially expressed fusion proteins. MyoB is concentrated at the leading edges of lamellipodia and at sites of cell-cell contact in both stationary and aggregation stage cells. Based on its distinctive appearance, we have named the myosin I-rich, interdigitating cell-cell contact structure in the stationary stage cells ''zipper''. To analyze the staining of filopodia, we employed the ratio imaging technique. We find that myoB is present in filopodia in either a uniform or an apical staining pattern. Like myoB, myoD is concentrated in leading edges of lamellipodia and at sites of cell-cell contact in stationary stage cells. MyoD is also present in filopodia, although the intensity is weaker than that of myoB staining. Despite persistence of myoD protein in the cells, myoD largely disappears from lamellipodia and cell-cell contact regions in aggregation stage cells, suggesting the occurrence of a developmentally regulated relocalization to the cytoplasm. While these results, along with the striking similarity in their tail domain structures, suggest that myoB and myoD have overlapping functions, differences in their localization in developing cells indicate that they have unique functions as well. C1 NORTHWESTERN UNIV,SCH MED,DEPT CELL & MOL BIOL,CHICAGO,IL 60611. NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [R0-1 GM-39548] NR 39 TC 29 Z9 31 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD DEC PY 1996 VL 71 IS 4 BP 371 EP 379 PG 9 WC Cell Biology SC Cell Biology GA VW820 UT WOS:A1996VW82000007 PM 8980908 ER PT J AU Chen, ZJ Shimizu, F Wheeler, J Notkins, AL AF Chen, ZJ Shimizu, F Wheeler, J Notkins, AL TI Polyreactive antigen-binding B cells in the peripheral circulation are IgD(+) and B7(-) SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B cell; B7; polyreactive B cell; IgD ID CD5+ LYMPHOCYTE-B; MONOCLONAL AUTOANTIBODIES; HIGH-AFFINITY; T-CELLS; RHEUMATOID-ARTHRITIS; NATURAL AUTOANTIBODY; ESCHERICHIA-COLI; PRESENTING CELLS; MULTIPLE ORGANS; CLONAL ANERGY AB Polyreactive antibodies are naturally occurring antibodies, primarily of the IgM isotype, that are capable of reacting with a wide variety of different self and nonself antigens. Previously we reported that a B cell capable of making polyreactive antibody has Ig receptors on its surface that can bind different antigens. The present investigation was initiated to characterize these polyreactive antigen-binding B cells further. A panel of fluorescein isothiocyanate-labeled antigens (insulin, IgG Fe fragment or beta-galactosidase) served as probes to select polyreactive antigen-binding B cells by cell sorting. Our experiment revealed that these polyreactive antigen-binding B cells were mainly of the IgD isotype. They expressed high levels of CD40 and major histocompatibility complex class II molecules, but little or no B7-1, B7-2, or Fas. In contrast to the binding of antigens to monoreactive receptors (usually high affinity), the binding of antigens to polyreactive receptors (usually moderate or low affinity) did not up-regulate the expression of B7-1 or B7-2. Antigens that bound to polyreactive receptors, however, were internalized and degraded, although not as efficiently as antigens that bound to monoreactive receptors. Despite the ability of these B7(-) cells to process antigens, they were not able to activate T cells in a mixed leukocyte reaction. It is concluded that polyreactive antigen-binding B cells have properties that are consistent with the ability to induce immunological tolerance. RP Chen, ZJ (reprint author), NIDR,ORAL MED LAB,NIH,BLDG 30,ROOM 121,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 49 TC 15 Z9 17 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1996 VL 26 IS 12 BP 2916 EP 2923 DI 10.1002/eji.1830261217 PG 8 WC Immunology SC Immunology GA VX140 UT WOS:A1996VX14000017 PM 8977286 ER PT J AU Andersson, KB Draves, KE Magaletti, DM Fujioka, S Holmes, KL Law, CL Clark, EA AF Andersson, KB Draves, KE Magaletti, DM Fujioka, S Holmes, KL Law, CL Clark, EA TI Characterization of the expression and gene promoter of CD22 in murine B cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B cell; CD22; tyrosine phosphorylation; B cell receptor; gene promoter ID SURFACE-IMMUNOGLOBULIN-M; MOUSE BONE-MARROW; LYMPHOCYTES-B; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; TYROSINE; ACTIVATION; LEUKEMIA; PHOSPHATASE; ADHESION AB CD22 is a B cell-restricted surface molecule which may play an important role in interactions between B cells and other cells and in regulating signals through the B cell receptor (BCR) complex. Were we have examined whether the mouse is a suitable in vivo model for studying CD22 functions. Tn primary and secondary lymphoid organs of adult mice CD22 is on all mature B cells, including resting IgM(+)IgD(+) B cells, IgG(+) HSA(lo) memory B cells, syndecan(+) plasma cells and CD5(+) B cells, but it is not on immature IgM(+)IgD(-) B cells. Biochemical, analysis revealed that murine CD22 is associated with the IgM receptor in some, but not all, CD22(+) B leukemic and lymphoma cell lines; as with human CD22, murine CD22 is rapidly phosphorylated on tyrosine after ligation of the BCR. In the CD22(-) murine pro-B cell line, FEMCL, CD22 expression was inducible by treatment with phorbol 32-myristate 13-acetate. A genomic fragment of the cd22(b) allele containing 1.3 kb 5' of exon 1 was sequenced in order to identify potential DNA regulatory elements in the CD22 promoter region. Consensus sequences for transcription factor binding sites including PU.1, BP-1, AP-2, C/EBP and SP-1 were present, but no classical TATA elements or initiator motifs were evident at relevant positions. The 1.3-kb promoter fragment 5' of exon 1 was sufficient for directing basal promoter activity in B and T cells. There was no significant sequence similarity between the murine and human cd22 gene promoters, although both contain repetitive elements and Sp-1 and AP1 binding sites. Thus, murine CD22 shares a number of features with human CD22 and the mouse provides a suitable model system for elucidating the function of CD22 in vivo. C1 UNIV WASHINGTON,MED CTR,DEPT MICROBIOL,SEATTLE,WA 98195. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RI Clark, Edward/K-3462-2012 FU NIDCR NIH HHS [DE08229]; NIGMS NIH HHS [GM42508] NR 50 TC 18 Z9 18 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1996 VL 26 IS 12 BP 3170 EP 3178 DI 10.1002/eji.1830261250 PG 9 WC Immunology SC Immunology GA VX140 UT WOS:A1996VX14000050 PM 8977319 ER PT J AU Tian, M Jacobson, C Gee, SH Campbell, KP Carbonetto, S Jucker, M AF Tian, M Jacobson, C Gee, SH Campbell, KP Carbonetto, S Jucker, M TI Dystroglycan in the cerebellum is a laminin alpha 2-chain binding protein at the glial-vascular interface and is expressed in Purkinje cells SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dystrophin; utrophin; merosin; synapse; vasculature; basement membrane; astrocytes; rat ID DUCHENNE MUSCULAR-DYSTROPHY; CENTRAL-NERVOUS-SYSTEM; EXTRACELLULAR-MATRIX; RAT-BRAIN; GLYCOPROTEIN COMPLEX; MEMBRANE-PROTEIN; AGRIN RECEPTOR; HIGH-AFFINITY; MOUSE; LOCALIZATION AB Dystroglycan is a core component of the dystrophin receptor complex in skeletal muscle which links the extracellular matrix to the muscle cytoskeleton. Dystrophin, dystrophin-related protein (DRP, utrophin) and dystroglycan are present not only in muscles but also in the brain. Dystrophin is expressed in certain neuronal populations while DRP is associated with perivascular astrocytes. To gain insights into the function and molecular interactions of dystroglycan in the brain, we examined the localization of alpha- and beta-dystroglycan at the cellular and subcellular levels in the rat cerebellum. In brood vessels, we find alpha-dystroglycan associated with the laminin alpha 2-chain-rich parenchymal vascular basement membrane and beta-dystroglycan associated with the endfeet of perivascular astrocytes. We also show that alpha-dystroglycan purified from the brain binds alpha 2-chain-containing laminin-2. These observations suggest a dystroglycan-mediated linkage between DRP in perivascular astrocytic endfeet and laminin-2 in the parenchymal basement membrane similar to that described in skeletal muscle. This linkage of the astrocytic endfeet to the vascular basement membrane is likely to be important for blood vessel formation and stabilization and for maintaining the integrity of the blood-brain barrier. In addition to blood vessel labelling, we show that alpha-dystroglycan in the rat cerebellum is associated with the surface of Purkinje cell bodies, dendrites and dendritic spines. Dystrophin has previously been localized to the inner surface of the plasmamembrane of Purkinje cells and is enriched at postsynaptic sites. Thus, the present results also support the hypothesis that dystrophin interacts with dystroglycan in cerebellar Purkinje neurons. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. MCGILL UNIV,MONTREAL GEN HOSP,RES INST,CTR RES NEUROSCI,MONTREAL,PQ H3G 1A4,CANADA. UNIV IOWA,COLL MED,HOWARD HUGHES MED INST,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242. NR 55 TC 102 Z9 104 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 1996 VL 8 IS 12 BP 2739 EP 2747 DI 10.1111/j.1460-9568.1996.tb01568.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA WH235 UT WOS:A1996WH23500030 PM 8996823 ER PT J AU Vacchiano, E Zelenka, PS AF Vacchiano, E Zelenka, PS TI Growth, differentiation and gene expression in primary cultures of embryonic chicken lens epithelial cells SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID C-JUN; MESSENGER-RNA; PROTEINS; MYC; FOS C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 16 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 1996 VL 63 IS 6 BP 753 EP 757 DI 10.1006/exer.1996.0169 PG 5 WC Ophthalmology SC Ophthalmology GA VZ417 UT WOS:A1996VZ41700016 PM 9068382 ER PT J AU Vawter, MP DillonCarter, O Tourtellotte, WW Carvey, P Freed, WJ AF Vawter, MP DillonCarter, O Tourtellotte, WW Carvey, P Freed, WJ TI TGF beta 1 and TGF beta 2 concentrations are elevated in Parkinson's disease in ventricular cerebrospinal fluid SO EXPERIMENTAL NEUROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BLOOD-BRAIN-BARRIER; MIDBRAIN DOPAMINERGIC-NEURONS; TGF-BETA; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; NERVOUS-SYSTEM; DIFFERENTIAL EXPRESSION; TOTAL PROTEIN; FACTOR-BETA-1 AB Transforming growth factor (TGF)beta plays a role in injury repair in sites surrounding brain injury. The present study tested the hypothesis that TGF beta 1 and TGF beta 2 levels in the postmortem CSF of patients with neurodegenerative disorders would be elevated compared to those in normal subjects. Free TGF beta 1 and total TGF beta 2 were measured by ELISA in postmortem ventricular cerebrospinal fluid (vCSF) of patients with Parkinson's disease (n = 30), Alzheimer's disease (n = 30), multiple sclerosis (n = 15), and schizophrenia (n = 12) and of normal controls (n = 16). In addition, albumin, IgG, and total protein in vCSF were measured. Both TGF beta 1 and TGF beta 2 were significantly different between groups (P < 0.002 and P < 0.001, respectively). Parkinson's disease vCSF showed significant increases in both TGF beta 1 (P = 0.015) and TGF beta 2 (P = 0.012) compared to normal controls. There was a trend for TGF beta 2 to be elevated in Alzheimer's disease and multiple sclerosis vCSFs, which failed to achieve significance. There were no differences between controls and schizophrenics in TGF beta 1 or TGF beta 2. Alzheimer's disease vCSF showed a significant decrease in protein compared to all other groups, which was not related to blood-brain barrier permeability, age, or autolysis differences. Evidence is presented suggesting that some TGF beta 1 may leak into the vCSF from plasma, Autopsy vCSF levels of TGF beta isoforms were found to be distinctly different from those reported for human serum, especially for TGF beta 2, which is undetectable in plasma. These results indicate that further in vivo studies of TGF beta 2 in the CSF of Parkinson's disease patients are warranted to determine the relationship between clinical status, medication, and TGF beta 2 concentrations. (C) 1996 Academic Press, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP Vawter, MP (reprint author), NIMH,SECT PRECLIN NEUROSCI,NEUROPSYCHIAT BRANCH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032, USA. FU NIA NIH HHS [AG10161, AG09466] NR 50 TC 83 Z9 87 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1996 VL 142 IS 2 BP 313 EP 322 DI 10.1006/exnr.1996.0200 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VV613 UT WOS:A1996VV61300009 PM 8934562 ER PT J AU Baldwin, W McCardle, P AF Baldwin, W McCardle, P TI Peer review at NIH in the 21st century SO FASEB JOURNAL LA English DT Editorial Material RP Baldwin, W (reprint author), NIH,OFF EXTRAMURAL RES,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 1996 VL 10 IS 14 BP 1563 EP 1568 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WC869 UT WOS:A1996WC86900001 PM 9002547 ER PT J AU Burg, MB Kwon, ED Kultz, D AF Burg, MB Kwon, ED Kultz, D TI Osmotic regulation of gene expression SO FASEB JOURNAL LA English DT Review DE osmolytes; heat shock genes; hypertonicity; signaling pathway ID ACTIVATED PROTEIN-KINASE; RENAL MEDULLARY CELLS; ALDOSE REDUCTASE GENE; MAP KINASE; SIGNAL-TRANSDUCTION; HIGH-OSMOLARITY; HYPERTONIC STRESS; ESCHERICHIA-COLI; TRANSPORTER GENE; MAMMALIAN-CELLS AB Cells react to increased osmolality with numerous changes in gene expression, The specific genes affected differ between species, but the known osmoprotective effects of the gene products are remarkably similar, particularly with regard to cellular accumulation of compatible organic osmolytes, Here we concentrate on the molecular basis for osmotic regulation of gene expression, emphasizing certain genes expressed in bacteria, yeast, and the mammalian renal medulla because their expression is best understood, Thus, we emphasize I) bacterial and yeast two-component histidine kinase systems, each consisting of a membrane osmolality sensor and a separate cytoplasmic response regulator that, when phosphorylated, alters transcription, 2) volume regulatory increases in cellular K+ salts that can prompt increased gene transcription in bacteria through direct effects on DNA and that in mammalian renal cells increase transcription, seemingly via trans-activating proteins, 3) a yeast kinase cascade that transmits an osmotic signal to the gene regulating the level of glycerol, and 4) in mammalian cells, several homologous cascades that are activated by hypertonicity, but whose osmoregulatory targets are not yet known. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 39 TC 139 Z9 142 U1 3 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 1996 VL 10 IS 14 BP 1598 EP 1606 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WC869 UT WOS:A1996WC86900005 PM 9002551 ER PT J AU Price, CJ Marr, MC Myers, CB Seely, JC Heindel, JJ Schwetz, BA AF Price, CJ Marr, MC Myers, CB Seely, JC Heindel, JJ Schwetz, BA TI The developmental toxicity of boric acid in rabbits SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID TESTICULAR TOXICITY; RATS; MICE; FETAL; FETUSES; BORON; BA AB Boric acid (BA), an ingredient of many pharmaceutical, cosmetic, and pesticide products, was previously shown to induce reproductive and developmental toxicity in laboratory rodents. In this study, BA (0, 62.5, 125, or 250 mg/kg/day, po) was administered on Gestational Days (GD) 6-19 to New Zealand White rabbits (18-23 pregnant/group). Maternal body weight, food consumption, and clinical condition were monitored at regular intervals throughout gestation. At termination (GD 30), the numbers of uterine implantations, resorptions, dead fetuses, and live fetuses were determined. Fetuses were weighed, and live fetuses examined for external, visceral, and skeletal defects. Maternal food intake decreased during treatment at 250 mg/kg/day and increased at greater than or equal to 125 mg/kg/day after treatment. Maternal body weight (CD 9-30), weight gain during treatment, gravid uterine weight, and number of ovarian corpora lutea decreased at 250 mg/kg/day. In contrast, maternal corrected gestational weight gain increased at greater than or equal to 125 mg/kg/day. Maternal liver weight was not affected. Relative (but not absolute) maternal kidney weight increased at 250 mg/ kg/day, and microscopic evaluation revealed no treatment-related renal pathology. At 250 mg/kg/day, prenatal mortality was increased (90% resorptions/litter vs 6% for controls), the proportion of pregnant females with no live fetuses was increased (73% vs 0%), and live litter size was reduced (2.3 fetuses/litter vs 8.8). As a result, there were only 14 live fetuses (6 live litters) available for evaluation in the high-dose group, compared to 153-175 live fetuses (18-23 live litters) in the other groups. The percentage malformed fetuses/litter was increased at 250 mg/kg/day, primarily due to cardiovascular defects in 72% of high-dose fetuses vs 3% of controls. The most prevalent cardiovascular malformation (interventricular septal defect) was observed in 57% of high-dose fetuses compared to 0.6% among controls. At 250 mg/kg/day, average fetal body weight/litter was 92% of the average control weight (not statistically significant). In summary, no definitive maternal or developmental toxicity was observed at 62.5 or 125 mg/kg/day BA. Mild maternal effects and severe developmental toxicity were observed at 250 mg/kg/day. (C) 1996 Society of Toxicology. C1 PATHCO INC,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. RP Price, CJ (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-95255] NR 58 TC 30 Z9 31 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD DEC PY 1996 VL 34 IS 2 BP 176 EP 187 DI 10.1006/faat.1996.0188 PG 12 WC Toxicology SC Toxicology GA VZ317 UT WOS:A1996VZ31700002 PM 8954748 ER PT J AU George, JD Price, CJ Marr, MC Myers, CB Schwetz, BA Heindel, JJ Hunter, ES AF George, JD Price, CJ Marr, MC Myers, CB Schwetz, BA Heindel, JJ Hunter, ES TI Evaluation of the developmental toxicity of methacrylonitrile in Sprague-Dawley rats and New Zealand White rabbits SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; TERATOGENICITY; FETUSES AB Timed-pregnant Sprague-Dawley (CD) outbred rats and New Zealand White rabbits were dosed by gavage with methacrylonitrile (MACR) in distilled water during major organogenesis. Rats were dosed on Gestational Days (GD) 6 through 15 (0, 5, 25, or 50 mg MACR/kg/day) and rabbits on GD 6 through 19 (0, 1, 3, or 5 mg MACR/kg/day). Maternal clinical status was monitored daily during treatment. At termination (GD 20, rats; GD 30, rabbits), confirmed-pregnant females (25-26 per group, rats; 17-22 per group, rabbits) were evaluated for clinical status and gestational outcome; each live fetus was examined for external, visceral, and skeletal malformations. In rats, no treatment-related maternal clinical signs or mortality were observed, nor was there any adverse effect on maternal body weight or food or water consumption. At necropsy, absolute, relative, and adjusted maternal liver weight was increased at the mid- and high-dose groups, an effect that may be indicative of induction of hepatic enzymes rather than toxicity. In the absence of any indication of maternal toxicity, the no-observed-adverse-effect level (NOAEL) for maternal toxicity in this study was greater than or equal to 50 mg MACR/kg/day. The NOAEL for developmental toxicity in rats was also greater than or equal to 50 mg MACR/kg/day. There was no effect of treatment on postimplantation loss, mean fetal body weight per litter, or morphological development. In rabbits, maternal mortality and clinical signs were not dose related. Maternal food consumption, body weight, and liver weight were not adversely affected by treatment. Thus, the maternal NOAEL was greater than or equal to 5 mg MACR/kg/day. Maternal toxicity, including death, was observed greater than or equal to 7.5 mg/kg/day in preliminary studies. The developmental NOAEL was also greater than or equal to 5 mg MACR/kg/day. There was no adverse effect of treatment on postimplantation loss or fetal body weight. A significant decrease in the percentage male fetuses per litter was observed, although there was no effect on total live litter size, suggesting that the reduction in the ratio of live male fetuses in the high-dose group was not biologically significant. MACR had no adverse effect on morphological development. In summary, oral administration of MACR to rats and rabbits during organogenesis, at doses that did not cause persistent maternal toxicity (50 mg MACR/kg/day, rats; 5 mg MACR/kg/day, rabbits), also did not cause any adverse developmental effects. (C) 1996 Society of Toxicology. C1 NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. RP George, JD (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-95255] NR 34 TC 3 Z9 3 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD DEC PY 1996 VL 34 IS 2 BP 249 EP 259 DI 10.1006/faat.1996.0194 PG 11 WC Toxicology SC Toxicology GA VZ317 UT WOS:A1996VZ31700008 PM 8954754 ER PT J AU Ross, GW Petrovitch, H White, LR AF Ross, GW Petrovitch, H White, LR TI Update on dementia SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; PREVALENCE; DIAGNOSIS; TRIAL C1 KUAKINI MED CTR,HONOLULU ASIA AGING STUDY,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,HONOLULU,HI 96822. NIA,ASIA PACIFIC OFF,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,HONOLULU,HI. RP Ross, GW (reprint author), HONOLULU VET AFFAIRS OUTPATIENT CLIN,HONOLULU,HI, USA. NR 25 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD WIN PY 1996 VL 20 IS 4 BP 22 EP 27 PG 6 WC Gerontology SC Geriatrics & Gerontology GA WC863 UT WOS:A1996WC86300006 ER PT J AU Elkahloun, AG Bittner, M Hoskins, K Gemmill, R Meltzer, PS AF Elkahloun, AG Bittner, M Hoskins, K Gemmill, R Meltzer, PS TI Molecular cytogenetic characterization and physical mapping of 12q13-15 amplification in human cancers SO GENES CHROMOSOMES & CANCER LA English DT Article ID ARTIFICIAL-CHROMOSOME LIBRARIES; HUMAN-MALIGNANT GLIOMAS; SOFT-TISSUE SARCOMAS; DNA-SEQUENCE; GENE; MDM2; REGION; MICRODISSECTION; YEAST; P53 AB Amplification of sequences derived from 12q13-15 is frequent in human sarcomas and brain tumors. Detailed mapping studies of the amplified region are necessary for definition of the impact of these amplification events on the tumor cell phenotype. By using the genes in this region and genomic fragments isolated by chromosome microdissection, we have established a series of ordered probes from 12q13-15 for fluorescence in situ hybridization (FISH) and Southern blot analysis. These probes have been used for physical mapping of two portions of the interval from GLI to D12S8. The centromeric region extends 1.8 Mb from GLI to microclone M79 and contains at least five genes, including the cyclin-dependent kinase gene CDK4. The more telomeric region includes the p53 regulator MDM2 and covers 1.1 Mb. We used the same group of probes to determine the pattern of amplification in three cell lines and three tumor specimens carrying amplified sequences from 12q13-15. In addition, we used a yeast artificial chromosome (YAC) contig of several megabases covering the entire region from SAS to D 12S8 for FISH to determine the pattern of amplification in the neuroblastoma cell line NGP-127. The results suggest that the MDM2 and CDK4 regions may be either coamplified or amplified independently, and they illustrate how the map positions of genes and their functions may interact to determine the pattern of DNA amplification in human malignancies. (C) 1996 Wiley-Liss, Inc.* C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT MED,ANN ARBOR,MI 48109. ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80206. NR 31 TC 58 Z9 59 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1996 VL 17 IS 4 BP 205 EP 214 DI 10.1002/(SICI)1098-2264(199612)17:4<205::AID-GCC2>3.0.CO;2-7 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VV693 UT WOS:A1996VV69300002 PM 8946202 ER PT J AU Berner, JM Forus, A Elkahloun, A Meltzer, PS Fodstad, O Myklebost, O AF Berner, JM Forus, A Elkahloun, A Meltzer, PS Fodstad, O Myklebost, O TI Separate amplified regions encompassing CDK4 and MDMZ in human sarcomas SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SOFT-TISSUE SARCOMAS; RETINOBLASTOMA PROTEIN; AMPLIFICATION UNITS; MESSENGER-RNA; GENE; IDENTIFICATION; RECEPTOR; TUMORS; GLI AB Amplification of MDM2 and CDK4 is observed frequently in human sarcomas. Although overexpression of these protooncogenes might inhibit growth regulation through the TP53- and retinoblastoma tumor suppressor protein (RB)-mediated pathways, neither gene was included consistently in all of the amplicons observed in our sarcoma panel. It was unclear whether both of these genes were selected for during amplification. Furthermore, in some samples without amplification of MDM2 or CDK4, comparative genomic hybridization showed amplification in the 12q13-15 region, suggesting that another selection mechanism might also be involved. To investigate the possibility that another target gene, which may be located between CDK4 and MDM2, could be the driving force, we characterized the involvement of 17 loci from this region in 12q13-15 amplicons that were detected previously in 21 sarcoma samples. The results showed discrete amplicons around MDM2 and CDK4 with reduced amplification of the intervening sequences. This suggests that there is separate selection for amplification of the two genes, and it makes the possibility of a common selective gene unlikely. Furthermore, D12S8, localized distal to MDM2, was amplified almost as frequently as MDM2 and was also amplified in one of the samples without MDM2 or CDK4 amplification. The data suggest that amplification of at least three different regions within the 12q13-15 segment may be selected for in tumor cells involving MDM2, CDK4, or a more distally located gene, possibly near D12S8. (C) 1996 Wiley-Liss, Inc. C1 NORWEGIAN RADIUM HOSP,DEPT TUMOR BIOL,N-0310 OSLO,NORWAY. NIH,NATL CTR GENOME RES,CANC GENET LAB,BETHESDA,MD. RI Myklebost, Ola/E-9335-2010 OI Myklebost, Ola/0000-0002-2866-3223 NR 33 TC 91 Z9 91 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1996 VL 17 IS 4 BP 254 EP 259 DI 10.1002/(SICI)1098-2264(199612)17:4<254::AID-GCC7>3.0.CO;2-2 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VV693 UT WOS:A1996VV69300007 PM 8946207 ER PT J AU Borchelt, DR Davis, J Fischer, M Lee, MK Slunt, HH Ratovitsky, T Regard, J Copeland, NG Jenkins, NA Sisodia, SS Price, DL AF Borchelt, DR Davis, J Fischer, M Lee, MK Slunt, HH Ratovitsky, T Regard, J Copeland, NG Jenkins, NA Sisodia, SS Price, DL TI A vector for expressing foreign genes in the brains and hearts of transgenic mice SO GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING LA English DT Article DE expression vector; transgenic; brain ID ALZHEIMERS-DISEASE; PRION PROTEIN; PRECURSOR PROTEIN; SCRAPIE; MUTATION; PEPTIDE; APP AB An expression plasmid (MoPrP.Xho), for use in transgenic mice, was developed from the promoter, 5' intronic, and 3' untranslated sequences of the murine prion protein gene. Analyses of mice harboring the MoPrP.Xho construct with cDNA genes encoding the amyloid precursor protein (APP) and human presenilin 1 demonstrated that this vector provides relatively high levels of transgene-encoded polypeptides in brains and hearts of transgenic mice. The MoPrP.Xho vector should be very useful in strategies designed to overexpress a variety of wild-type and disease related mutant transgenes in the heart and brain. (C) 1996 Elsevier Science B.V. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. UNIV ZURICH,INST MOL BIOL,ABT 1,CH-8093 ZURICH,SWITZERLAND. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Borchelt, DR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,720 RUTLAND AV,558 ROSS BLDG,BALTIMORE,MD 21205, USA. RI Lee, Michael/D-9491-2013 OI Lee, Michael/0000-0001-5865-9682 NR 19 TC 255 Z9 256 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1050-3862 J9 GENET ANAL-BIOMOL E JI Genet. Anal.-Biomol. Eng. PD DEC PY 1996 VL 13 IS 6 BP 159 EP 163 DI 10.1016/S1050-3862(96)00167-2 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WG494 UT WOS:A1996WG49400004 PM 9117892 ER PT J AU Erbelding, EJ Quinn, TC AF Erbelding, EJ Quinn, TC TI The clinical utility of viral load monitoring in HIV infection: Strengths and limitations SO GENITOURINARY MEDICINE LA English DT Editorial Material ID PLASMA C1 NIH,NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,DEPT MED,BALTIMORE,MD 21205. NR 17 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0266-4348 J9 GENITOURIN MED JI Genitourin. Med. PD DEC PY 1996 VL 72 IS 6 BP 393 EP 395 PG 3 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Urology & Nephrology SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Urology & Nephrology GA WA440 UT WOS:A1996WA44000001 PM 9038632 ER PT J AU Smoot, DT Resau, JH Earlington, MH Simpson, M Cover, TL AF Smoot, DT Resau, JH Earlington, MH Simpson, M Cover, TL TI Effects of Helicobacter pylori vacuolating cytotoxin on primary cultures of human gastric epithelial cells SO GUT LA English DT Article DE H pylori; vacuolating cytotoxin; human gastric cell culture ID ENHANCED TOXICITY; HELA-CELLS; TOXIN; INFECTION; DISEASE; INHIBITORS; CARCINOMA; ADHERENT; STRAINS; RISK AB Background-Many Helicobacter pylori strains produce a cytotoxin that induces cytoplasmic vacuolation in various types of eukaryotic cells. In contrast with the marked cell vacuolation that occurs in vitro in response to this cytotoxin, comparatively Little epithelial vacuolation has been observed in the gastric mucosa of H pylori infected persons. Aims-Experiments were performed to determine the susceptibility of human gastric epithelial cells in vitro to H pylori vacuolating cytotoxin activity. Methods-Human gastric epithelial cells, harvested from upper gastrointestinal endoscopic biopsy specimens, were incubated overnight with broth culture supernatants from either a wild type cytotoxin producing (tox(+)) H pylori strain or an isogenic mutant strain that lacks cytotoxin activity. Results-Prominent cytoplasmic vacuolation occurred in response to tox(+) supernatant, but not supernatant from the isogenic mutant strain. Primary human gastric epithelial cells were significantly more sensitive to H pylori vacuolating cytotoxin activity than were either HeLa or AGS cells, Exposure of human gastric epithelial cells to high concentrations of tox(+) supernatant for 48 hours caused lethal cell injury. Conclusions-These studies indicate that primary human gastric epithelial cells are highly sensitive to H pylori vacuolating cytotoxin activity. C1 HOWARD UNIV,COLL MED,DEPT MED,DIV GASTROENTEROL,WASHINGTON,DC 20059. VANDERBILT UNIV,DEPT MED,DIV INFECT DIS,NASHVILLE,TN. VET AFFAIRS MED CTR,NASHVILLE,TN 37212. NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. FU NIGMS NIH HHS [GM08244] NR 28 TC 37 Z9 38 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD DEC PY 1996 VL 39 IS 6 BP 795 EP 799 DI 10.1136/gut.39.6.795 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WD466 UT WOS:A1996WD46600004 PM 9038659 ER PT J AU Herman, AA Berendes, HW Yu, KF Cooper, LC Overpeck, MD Rhoads, G Maxwell, JP Kinney, BA Koslowe, PA Coates, DL AF Herman, AA Berendes, HW Yu, KF Cooper, LC Overpeck, MD Rhoads, G Maxwell, JP Kinney, BA Koslowe, PA Coates, DL TI Evaluation of the effectiveness of a community-based enriched model prenatal intervention project in the District of Columbia SO HEALTH SERVICES RESEARCH LA English DT Article DE prenatal care; evaluation; low birth weight; very low birth weight ID LOW-BIRTH-WEIGHT; INFANT-MORTALITY; NORTH-CAROLINA; UNITED-STATES; CARE; IMPACT; POPULATION; MORBIDITY; MOTHERS; HEALTH AB Objective. To evaluate an enriched prenatal intervention program designed to reduce the risk of low birth weight. Study Setting. Freestanding community-based prenatal intervention project located in a poor inner-city community, serving mostly African American women. Study Design. All women less than 29 weeks pregnant were eligible to participate. They were compared to women who lived in neighborhoods with similar rates of poverty. Data Collection. The birth certificate was the source of data on maternal age, education, marital status, timing and frequency of prenatal care attendance, parity, gravidity, prior pregnancy terminations, fetal and child deaths, and birth weight. Principal Findings. Thirty-eight percent of the women who delivered live-born infants in the study area participated in the program. There were no differences in low- and very low birthweight rates in the study and comparison groups. In a secondary analysis comparing participants and nonparticipants in the study census tracts, participants were at higher risk for low and very low birth weight, and they adhered more closely to the schedule of prenatal visits than nonparticipants. Low- and very low birthweight rates were lower among participants than among nonparticipants and comparison women. Conclusion. The Better Babies Project did not have an effect on the overall low- and very low birthweight rates in the study census tracts. This was probably due to the low participation rates and the high population mobility. C1 NIDA,DIV EPIDEMIOL STAT & PREVENT RES,NIH,LEXINGTON,KY 40583. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT COMMUNITY & ENVIRONM MED,NEWARK,NJ 07103. COMP DATA SYST INC,ROCKVILLE,MD 20850. CUNY,CCNY,DEPT PSYCHOL,NEW YORK,NY 10021. INST BASIC RES DEV DISABIL,NEW YORK,NY. RP Herman, AA (reprint author), NICHHD,EPIDEMIOL BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,NIH,6100 EXECUT BLVD,ROCKVILLE,MD 20852, USA. FU NICHD NIH HHS [N01-HD-7-2922]; PHS HHS [MCJ-110558] NR 20 TC 12 Z9 12 U1 0 U2 0 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 1996 VL 31 IS 5 BP 609 EP 621 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA VV160 UT WOS:A1996VV16000007 PM 8943993 ER PT J AU Cheson, BD AF Cheson, BD TI Perspectives on purine analogues SO HEMATOLOGY AND CELL THERAPY LA English DT Review DE fludarabine; cladribine; pentostatin; CLL; NHL ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; NON-HODGKINS-LYMPHOMA; LOW-GRADE LYMPHOMA; CONTINUOUS-INFUSION SCHEDULE; PREVIOUSLY TREATED PATIENTS; PHASE-II TRIAL; TERM FOLLOW-UP; FLUDARABINE PHOSPHATE; 2-CHLORODEOXYADENOSINE TREATMENT AB The purine analogs, fludarabine, 2-chlorodeoxy-adenosine, and 2'-deoxycoformycin, have revolutionized our approach to the treatment of a variety of indolent lymphoid malignancies. Because of their impressive single agent activity, they should be considered as an initial therapeutic option, not only for hairy cell leukemia, but also for chronic lymphocytic leukemia, indolent non-Hodgkin's lymphomas, and Waldenstrom's macroglobulinemia. Combinations of purine analogs with alkylatng agents, topisomerase II inhibitors, and other new compounds are in development, and their role as radiation sensitizers is being explored in clinical trials. Substantial activity has also been noted in several of the rheumatologic and immunologic disorders, and in multiple sclerosis. Continued progress requires innovative strategies which can modulate the biology and immunology of these diseases toward the goal of curing these patients. RP Cheson, BD (reprint author), NCI, CANC THERAPY EVALUAT PROGRAM, EXECUT PLAZA N, RM 741, BETHESDA, MD 20892 USA. NR 104 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1269-3286 J9 HEMATOL CELL THER JI Hematol. Cell Ther. PD DEC PY 1996 VL 38 SU 2 BP S109 EP S116 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA WA465 UT WOS:A1996WA46500009 PM 9137964 ER PT J AU Eckman, JR AF Eckman, JR TI Leg ulcers in sickle cell disease SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ZINC SULPHATE; FREE FLAP; ANEMIA; THALASSEMIA; HYDROXYUREA; ULCERATION; PATIENT; PENTOXIFYLLINE; ANTIBIOTICS; DEFICIENCY AB Leg ulcers are a frequent complication in patients with sickle cell anemia and S/beta thalassemia causing significant physical disability and negative psychologic and social impact. Systematic conservative approaches to treatment using gentle debridement and control of edema result in rapid healing of most ulcers. Chronic recalcitrant ulcers are a challenge to the clinician and patient. Controlled clinical trials are not available to fully define the therapeutic approach to the chronic leg ulcers. C1 EMORY UNIV,GRADY MEM HOSP,SCH MED,COMPREHENS SICKLE CELL CTR,GEORGIA NIH,DIV HEMATOL ONCOL,ATLANTA,GA 30322. EMORY UNIV,GRADY MEM HOSP,SCH MED,COMPREHENS SICKLE CELL CTR,GEORGIA NIH,DIV MED GENET,ATLANTA,GA 30322. FU NHLBI NIH HHS [HL48482] NR 74 TC 32 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1996 VL 10 IS 6 BP 1333 EP & DI 10.1016/S0889-8588(05)70404-4 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA VX657 UT WOS:A1996VX65700010 PM 8956020 ER PT J AU Mason, A Sallie, R Perrillo, R Rayner, A Xu, LZ Dohner, DE Dehner, M Naoumov, N Gelb, L Saha, B OGrady, J Williams, R AF Mason, A Sallie, R Perrillo, R Rayner, A Xu, LZ Dohner, DE Dehner, M Naoumov, N Gelb, L Saha, B OGrady, J Williams, R TI Prevalence of herpesviridae and hepatitis B virus DNA in the liver of patients with non-A, non-B fulminant hepatic failure SO HEPATOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD; CYTOMEGALO-VIRUS; C VIRUS; SERUM; VARICELLA; TISSUES; ADULT; MONONUCLEOSIS; INFECTION AB Members of the herpes virus family and hepatitis B virus (HBV) have been implicated as etiologic agents in non-A, non-B (NANB) fulminant hepatic failure (FHF), but the frequency of infection with these agents has not been established using appropriate controls, To examine this issue, we studied 50 NANB FHF patients and 104 liver transplant recipients from North America and Europe. Hepatic DNA was analyzed by polymerase chain reaction (PCR) for evidence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus I (HSV I) and II (HSV II), varicella-zoster virus (VZV), and human herpes virus-6 (HHV-6) nucleic acid sequences. The prevalence of HBV was assessed in North American subjects only. Hm I, Hm II, VZV, and HHV-6 viral sequences were not observed in any samples. Three of 50 PHF (6%) and 14 of 104 control patients (13%) were positive for CMV DNA. Two of 50 FHF (4%) and 10 of 104 control patients (10%) had EBV DNA and REV DNA was observed in 3 of 10 North American EHF patients (30%) and 3 of 59 controls (5%) without serum markers for HBV infection, The finding of HBV DNA in the liver of seronegative controls from North America but not Europe suggests that occult hepatitis B sequences in patients with NANB FHF may simply reflect geographic differences. The majority of cryptogenic FHF cases cannot be attributed to infection with herpes viruses or HBV. C1 ALTON OCHSNER MED INST,SECT GASTROOENTEROL & HEPATOL,NEW ORLEANS,LA 70121. NATL INST HLTH,BETHESDA,MD. UNIV LONDON KINGS COLL HOSP,INST LIVER STUDIES,LONDON,ENGLAND. VAMC,ST LOUIS,MO. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. OI Mason, Andrew/0000-0002-0470-9522 NR 42 TC 28 Z9 31 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1996 VL 24 IS 6 BP 1361 EP 1365 DI 10.1002/hep.510240608 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VW778 UT WOS:A1996VW77800008 PM 8938162 ER PT J AU Liang, TJ AF Liang, TJ TI Hepatology elsewhere SO HEPATOLOGY LA English DT Editorial Material RP Liang, TJ (reprint author), NIDDK,NIH,LIVER DIS SECT,BLDG,10-9 B16,10 CTR DR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1996 VL 24 IS 6 BP 1536 EP 1537 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VW778 UT WOS:A1996VW77800038 ER PT J AU Ogawa, S Gordan, JD Taylor, J Lubahn, D Korach, K Pfaff, DW AF Ogawa, S Gordan, JD Taylor, J Lubahn, D Korach, K Pfaff, DW TI Reproductive functions illustrating direct and indirect effects of genes on behavior SO HORMONES AND BEHAVIOR LA English DT Article ID SEXUAL-BEHAVIOR; FEMALE RAT; RECEPTOR; ESTROGEN; INHIBITION; MICE AB Effects of gene products on reproductive behavior which are relatively direct include those of the estrogen receptor and progesterone receptor. For example, work with estrogen receptor-deficient (ERKO) female mice has extended previous evidence contributing to the neurochemical analysis of lordosis behavior. On the other hand, sex differences in behavior present a classic example of indirect effects of genes on behavior. Work with ERKO male mice shows the necessity of ER gene expression for normal masculinization of the brain. In particular, behavioral assay results distinguish apparent motivational performance of ERKO males from male mating reflexes: the former is similar to that of wild-type males in important respects, while the latter are deficient in ERKO males. The present paper first reviews a small number of clear genetic contributions to reproductive behaviors, and then reports one experiment pertinent to the interpretation of the behavioral status of ERKO male mice. (C) 1996 Academic Press. C1 ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,NEW YORK,NY 10021. UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65211. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X FU NICHD NIH HHS [HD-05751] NR 21 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 0018-506X J9 HORM BEHAV JI Horm. Behav. PD DEC PY 1996 VL 30 IS 4 BP 487 EP 494 DI 10.1006/hbeh.1996.0052 PG 8 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA WK515 UT WOS:A1996WK51500016 PM 9047273 ER PT J AU Lisziewicz, J Sun, D Gallo, RC Ensoli, B Lori, F AF Lisziewicz, J Sun, D Gallo, RC Ensoli, B Lori, F TI Efficacy of antitat gene therapy in the presence of high multiplicity infection and inflammatory cytokines SO HUMAN GENE THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; TYPE-1 TAT PROTEIN; HUMAN T-CELLS; KAPOSIS-SARCOMA; FACTOR-ALPHA; HIV-INFECTION; ENDOTHELIAL-CELLS; AIDS PATIENTS; EXPRESSION AB Because human immunodeficiency virus type 1 (HIV-1) infection is characterized by a large number of viral replication cycles and rapid cell turnover in vivo, successful gene therapy requires an approach effective under these conditions, The antitat gene has been proposed for gene therapy because it effectively blocks Tat function and the replication of HIV-1, However, neither antitat nor any other antiviral gene has been shown to inhibit HIV in the presence of high viral load and inflammatory cytokines, a condition closer to the in vivo situation, We show that cells transduced with antitat retrovirus vector are resistant to high multiplicity of HIV infection, In the presence of inflammatory cytokines, including interleukin-l and tumor necrosis factor, both known to activate viral gene expression independently of Tat, antitat suppressed virus replication, HIV-1 inhibition was observed when cell were treated with a mixture of inflammatory cytokines able to induce acquired immunodeficiency syndrome (AIDS) Kaposi's sarcoma cell growth, These molecules have been shown to be increased in HIV-1-infected individuals, and it is suggested they play a role in the pathogenesis of AIDS, Our results suggest that antitat is effective under conditions present in vivo and therefore a primary candidate for HIV-1 gene therapy. C1 UNIV PAVIA, POLICLIN SAN MATTEO, IRCCS, RES INST GENET & HUMAN THERAPY, I-27100 PAVIA, ITALY. NCI, TUMOR CELL BIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. UNIV MARYLAND, MARYLAND BIOTECHNOL INST, CTR MED BIOTECHNOL, INST HUMAN VIROL, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. RP Lisziewicz, J (reprint author), RES INST GENET & HUMAN THERAPY, 7965 CESSNA AVE, GAITHERSBURG, MD 20879 USA. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 39 TC 6 Z9 6 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 DEC 1 PY 1996 VL 7 IS 18 BP 2209 EP 2216 DI 10.1089/hum.1996.7.18-2209 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD329 UT WOS:A1996WD32900003 PM 8953311 ER PT J AU OConnell, BC Xu, T Walsh, TJ Sein, T Mastrangeli, A Crystal, RG Oppenheim, FG Baum, BJ AF OConnell, BC Xu, T Walsh, TJ Sein, T Mastrangeli, A Crystal, RG Oppenheim, FG Baum, BJ TI Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands SO HUMAN GENE THERAPY LA English DT Article ID HISTIDINE-RICH-POLYPEPTIDES; HUMAN ADENOVIRUS TYPE-5; CANDIDA-ALBICANS; CELL-LINE; ANTIFUNGAL ACTIVITY; PAROTID SECRETION; THERAPY; DRUGS; DNA AB Mucosal candidiasis, the most common opportunistic fungal infection in human immunodeficiency virus (HIV)-infected patients, is an early sign of clinically overt acquired immunodeficiency syndrome (AIDS) and an important cause of morbidity, particularly in HIV-infected children, The appearance of azole-resistant strains of Candida albicans had made clinical management of candidiasis increasingly difficult, We propose a novel approach to the management of candidal infections that involves the use of naturally occurring antifungal proteins, such as the histatins, Histatins are a family of small proteins that are secreted in human saliva, We have constructed recombinant adenovirus vectors that contain the histatin 3 cDNA, These vectors are capable of directing the expression of histatin 3 in the saliva of rats at up to 1,045 mu g/ml, well above the levels found in normal human saliva, The adenovirus-directed histatin demonstrated a 90% candidacidal effect in the timed-kill assay against both fluconazole-susceptible and fluconazole-resistant strains of C. albicans and inhibited germination by 45% in the same strains, These studies suggest that a gene transfer approach to overexpress naturally occurring antifungal proteins may be useful in the management of mucosal candidiasis. C1 BOSTON UNIV,SCH DENT MED,DEPT PERIODONTOL & ORAL BIOL,BOSTON,MA 02118. NCI,MYCOL UNIT,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP OConnell, BC (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,NATL INST HLTH,10 CTR DR,MSC 1190,BETHESDA,MD 20892, USA. OI O'Connell, Brian/0000-0003-4529-7664 FU NIDCR NIH HHS [DE0 7652, DE0 5672] NR 31 TC 62 Z9 62 U1 0 U2 2 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 DEC 1 PY 1996 VL 7 IS 18 BP 2255 EP 2261 DI 10.1089/hum.1996.7.18-2255 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD329 UT WOS:A1996WD32900008 PM 8953316 ER PT J AU Renbaum, P Duh, FM Latif, F Zbar, B Lerman, MI Kuzmin, I AF Renbaum, P Duh, FM Latif, F Zbar, B Lerman, MI Kuzmin, I TI Isolation and characterization of the full-length 3' untranslated region of the human von Hippel-Lindau tumor suppressor gene SO HUMAN GENETICS LA English DT Article ID RENAL-CARCINOMA; SOMATIC MUTATIONS; DNA METHYLATION; IDENTIFICATION; PHENOTYPE; CONTAINS; SEQUENCE; PROTEIN; REPEAT AB We have isolated the 3' untranslated region (3'UTR) of the human von Hippel-Lindau (VHL) tumor suppressor gene from a P1 phage containing the entire VHL genomic sequence. Several putative noncanonical (ATTAAA) poly(A) signals were identified, and the functional significance of these signals was examined by preparing VHL mammalian expression constructs with this DNA fragment and the previously isolated partial cDNA. Northern blot analysis from transfected renal carcinoma cells showed that both the endogenous and transgene VHL transcripts were the same length. Use of VHL transgene deletion mutants indicated that an ATTAAA sequence located between nucleotide (nt) +4237 and nt +4379 most likely serves as an active poly(A) signal in renal carcinoma cells, yielding a 3.6-kb 3'UTR. This work indicates that, together with the 5'UTR and the coding region, these sequences comprise the full-length human VHL cDNA. Sequence analysis revealed a 300- to 600-bp region conserved in human, murine, and rat VHL UTRs. In addition, the human 3'UTR was extremely rich in Alu repetitive elements. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. SHAARE ZEDEK MED CTR,DEPT GENET INTERNAL MED A,IL-91031 JERUSALEM,ISRAEL. RP Renbaum, P (reprint author), NCI,IMMUNOBIOL LAB,FREDERICK CANC RES & DEV CTR,BLDG 560,RM 12-71,FREDERICK,MD 21702, USA. NR 28 TC 32 Z9 33 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1996 VL 98 IS 6 BP 666 EP 671 DI 10.1007/s004390050281 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VT558 UT WOS:A1996VT55800009 PM 8931697 ER PT J AU Trask, BJ Mefford, H vandenEngh, G Massa, HF Juyal, RC Potocki, L Finucane, B Abuelo, DN Witt, DR Magenis, E Baldini, A Greenberg, F Lupski, JR Patel, PI AF Trask, BJ Mefford, H vandenEngh, G Massa, HF Juyal, RC Potocki, L Finucane, B Abuelo, DN Witt, DR Magenis, E Baldini, A Greenberg, F Lupski, JR Patel, PI TI Quantification by flow cytometry of chromosome-17 deletions in Smith-Magenis syndrome patients SO HUMAN GENETICS LA English DT Article ID CONTIGUOUS-GENE SYNDROME; IN-SITU HYBRIDIZATION; HEREDITARY NEUROPATHY; INTERSTITIAL DELETION; PRESSURE PALSIES; (17)(P11.2P11.2); RESOLUTION; DEL(17)(P11.2); BREAKPOINTS; LIABILITY AB We have used bivariate flow karyotyping to quantify the deletions involving chromosome 17 in sixteen patients with Smith-Magenis syndrome (SMS). The fluorescence intensities of mitotic chromosomes stained with Hoechst 33258 and chromomycin were quantified in a dual-beam flow cytometer. For each patient, the position of the peak representing the deleted chromosome 17 was compared to those of the normal homologs of an unaffected parent. The patients could be classified into four groups based on the size of their deletions. The deletions ranged from similar to 9-10 Mb (similar to 10-11% of the chromosome) to below the detection limit of the technique (2 Mb). Different deletion sizes were detected among patients whose high-resolution banding results were similar. Some deletions detected by banding were not detected by flow analyses. Deletion estimates are largely consistent with the results of molecular analyses. Patients with larger deletions that extend into band 17p12 have abnormal electrophysiologic studies of peripheral nerves. Deletion size does not appear to correlate with the degree of mental retardation, presence of behavioral abnormalities, craniofacial anomalies or common skeletal findings in SMS. By identifying patients with varying deletion sizes, these data will aid die construction of a long-range deletion-based map of 17p11.2 and identification of the genes involved in this syndrome. C1 RHODE ISL HOSP,GENET COUNSELING CTR,PROVIDENCE,RI 02903. OREGON HLTH SCI UNIV,CHILD DEV REHABIL CTR,PORTLAND,OR 97201. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,DIV NEUROSCI,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. ELWYN INC,ELWYN,PA 19063. KAISER PERMANENTE,DEPT GENET,SAN JOSE,CA 95119. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Trask, BJ (reprint author), UNIV WASHINGTON,DEPT MOL BIOTECHNOL,BOX 357730,SEATTLE,WA 98195, USA. RI genes, anthony/F-2541-2012 FU NCRR NIH HHS [MO1 RR-00188]; NICHD NIH HHS [HD28458] NR 39 TC 36 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1996 VL 98 IS 6 BP 710 EP 718 DI 10.1007/s004390050291 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA VT558 UT WOS:A1996VT55800019 PM 8931707 ER PT J AU Carrington, M Wade, J AF Carrington, M Wade, J TI Selection of transplant donors based on MHC microsatellite data (vol 51, pg 106, 1996) SO HUMAN IMMUNOLOGY LA English DT Correction, Addition ID CLASS-II REGION; H-Y; SEQUENCE; ANTIGEN; GENES; DNA; IDENTIFICATION; RECOMBINATION; D6S105; MAP C1 UNIV TORONTO,FAC MED,TTH REG HISTOCOMPATIBIL LAB,TORONTO,ON,CANADA. RP Carrington, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 23 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 1996 VL 51 IS 2 BP 106 EP 109 DI 10.1016/S0198-8859(96)00268-6 PG 4 WC Immunology SC Immunology GA VX306 UT WOS:A1996VX30600008 PM 8960914 ER PT J AU Li, YN Gulati, S Baker, PJ Brody, LC Banerjee, R Kruger, WD AF Li, YN Gulati, S Baker, PJ Brody, LC Banerjee, R Kruger, WD TI Cloning, mapping and RNA analysis of the human methionine synthase gene SO HUMAN MOLECULAR GENETICS LA English DT Article ID ARTERIAL OCCLUSIVE DISEASES; ENDOTHELIAL-CELL INJURY; NEURAL-TUBE DEFECTS; RISK FACTOR; VASCULAR-DISEASE; PLASMA HOMOCYSTEINE; HYPERHOMOCYSTEINEMIA; METABOLISM; CANCER; HOMOCYST(E)INE AB Elevated levels of plasma homocysteine is a risk factor in both birth defects and vascular disease. Methionine synthase (MS) is a cobalamin dependent enzyme which catalyzes methylation of homocysteine to methionine. Impaired MS activity is expected to lead to increased levels of plasma homocysteine. In addition, defects in this gene may underlie the methionine-dependence observed in a number of human tumor cell lines, We describe here the isolation and characterization of the human MS cDNA. It contains an open reading frame of 3798 nucleotides encoding a protein of 1265 amino acids with a predicted molecular mass of 140 kDa. The amino acid sequence of the human MS is 55% identical with that of the Escherichia coli enzyme (METH) and 64% identical with the predicted Caenorhabditis elegans enzyme, Seven peptide sequences derived from purified porcine MS have substantial similarity to the human protein, Northern analysis indicates that the MS RNA is present in a wide variety of tissues. We have mapped the human gene to chromosomal location 1q43, a region found monosomic in individuals with deletion 1q syndrome. The isolation of the MS cDNA will now allow the direct determination of whether mutations in this gene contribute to folate-related neural tube defects, cardiovascular diseases, and birth defects. C1 FOX CHASE CANC CTR,DIV POPULAT SCI,PHILADELPHIA,PA 19046. UNIV NEBRASKA,DEPT BIOCHEM,LINCOLN,NE 68588. NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. RI kruger, warren/A-6407-2008 OI kruger, warren/0000-0002-4990-3695 FU NCI NIH HHS [CA-06927]; NIDDK NIH HHS [DK45776] NR 35 TC 94 Z9 96 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1996 VL 5 IS 12 BP 1851 EP 1858 DI 10.1093/hmg/5.12.1851 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VX747 UT WOS:A1996VX74700001 PM 8968735 ER PT J AU Gulati, S Baker, P Li, YN Fowler, B Kruger, W Brody, LC Banerjee, R AF Gulati, S Baker, P Li, YN Fowler, B Kruger, W Brody, LC Banerjee, R TI Defects in human methionine synthase in cblG patients SO HUMAN MOLECULAR GENETICS LA English DT Article ID ESCHERICHIA-COLI; COBALAMIN; HETEROGENEITY; BINDING; DEFICIENCY; MUTATION AB Inborn errors resulting in isolated functional methionine synthase deficiency fall into two complementation groups, cblG and cblE. Using biochemical approaches we demonstrate that one cblG patient has greatly reduced levels of methionine synthase while in another, the enzyme is specifically impaired in the reductive activation cycle, The biochemical data suggested that low levels of methionine synthase activity in the first patient may result from mutations in the catalytic domains of the enzyme, reduced transcription, or generation of unstable message or protein, Using Northern analysis, we demonstrate that the molecular basis for the biochemical phenotype in this patient is associated with greatly diminished steady-state levels of methionine synthase mRNA, The biochemical data on the second patient cell line implicated mutations specific to reductive activation, a function that is housed in the C-terminal AdoMet-binding domain and the intermediate B-12-binding domain, in the highly homologous bacterial enzyme, We have detected two mutations in a compound heterozygous state, one that results in conversion of a conserved proline (1173) to a leucine residue and the other a deletion of an isoleucine residue (881), The crystal structure of the C-terminal domain of the Escherichia coli MS predicts that the Pro to Leu mutation could disrupt activation since it is embedded in a sequence that makes direct contacts with the bound AdoMet, Deletion of isoleucine in the B-12-binding domain would result in shortening of a beta-sheet, Our data provide the first evidence for mutations in the methionine synthase gene being culpable for the cblG phenotype. In addition, they suggest directly that mutations in methionine synthase can lead to elevated homocysteine, implicated both in neural tube defects and in cardiovascular diseases. C1 UNIV NEBRASKA,DEPT BIOCHEM,LINCOLN,NE 68588. NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. FOX CHASE CANC CTR,DIV POPULAT SCI,PHILADELPHIA,PA 19046. UNIV BASEL,KINDERKLIN,CH-4005 BASEL,SWITZERLAND. RI kruger, warren/A-6407-2008 OI kruger, warren/0000-0002-4990-3695 FU NIDDK NIH HHS [DK45776] NR 17 TC 78 Z9 81 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1996 VL 5 IS 12 BP 1859 EP 1865 DI 10.1093/hmg/5.12.1859 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VX747 UT WOS:A1996VX74700002 PM 8968736 ER PT J AU Gilad, S BarShira, A Harnik, R Shkedy, D Ziv, Y Khosravi, R Brown, K Vanagaite, L Xu, G Frydman, M Lavin, MF Hill, D Tagle, DA Shiloh, Y AF Gilad, S BarShira, A Harnik, R Shkedy, D Ziv, Y Khosravi, R Brown, K Vanagaite, L Xu, G Frydman, M Lavin, MF Hill, D Tagle, DA Shiloh, Y TI Ataxia-telangiectasia: Founder effect among North African Jews SO HUMAN MOLECULAR GENETICS LA English DT Article ID SMALL GEOGRAPHIC AREA; METACHROMATIC LEUKODYSTROPHY; SINGLE ORIGIN; GENE; MUTATIONS; FAMILIES; CANCER; ISRAEL AB The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition, A-T carriers were reported to be moderately cancer-prone, A wide variety of A-T mutations, most of which are unique to single families, were identified in various ethnic groups, precluding carrier screening with mutation-specific assays, However, a single mutation was observed in 32/33 defective ATM alleles in Jewish A-T families of North African origin, coming from various regions of Morocco and Tunisia, This mutation, 103C-->T, results in a stop codon at position 35 of the ATM protein. In keeping with the nature of this mutation, various antibodies directed against the ATM protein failed to detect this protein in patient cells, A rapid carrier detection assay detected this mutation in three out of 488 ATM alleles of Jewish Moroccan or Tunisian origin. This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community. C1 TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN GENET, IL-69978 RAMAT AVIV, ISRAEL. NIH, CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. ONCOGENE RES PROD, CAMBRIDGE, MA 02142 USA. CHAIM SHEBA MED CTR, INST HUMAN GENET, IL-52621 TEL HASHOMER, ISRAEL. QUEENSLAND INST MED RES, HERSTON, QLD 4006, AUSTRALIA. RI Lavin, Martin/F-5961-2014 OI Lavin, Martin/0000-0002-5940-4769 FU NINDS NIH HHS [NS31763] NR 33 TC 79 Z9 79 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1996 VL 5 IS 12 BP 2033 EP 2037 DI 10.1093/hmg/5.12.2033 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VX747 UT WOS:A1996VX74700026 PM 8968760 ER PT J AU Hollingsworth, HC Steinberg, SM Silverberg, SG Merino, MJ AF Hollingsworth, HC Steinberg, SM Silverberg, SG Merino, MJ TI Advanced stage transitional cell carcinoma of the ovary SO HUMAN PATHOLOGY LA English DT Article DE ovary; carcinoma; transitional cell carcinoma ID BRENNER TUMORS; CHEMOTHERAPY; CISPLATIN AB Primary transitional cell carcinoma (TCC) of the ovary has been recently recognized as a separate subtype of epithelial cancer. It has been proposed that recognition of such tumors is important on clinical grounds because of a favorable response to chemotherapy and an improved patient survival. The authors reviewed the histological and clinicopathologic findings of 58 patients with advanced stage (stages III and IV) ovarian cancer with a view to determining the frequency of TCC and confirming the favorable prognosis. Of these cases, 15 (26%) were reclassified as TCC; 13 were predominantly TCC, and 2 had a mixed pattern with approximately 50% of the tumor being TCC. TCC patients ranged in age from 44 to 70 years of age (mean, 57). Ten of the patients had stage III disease, and five were stage IV. The tumor was unilateral in 2 cases and bilateral in 11 (2 unknown). Tumor size varied between 3 and 23 cm. Of the stage III patients, five were optimally debulked, and five had residual disease. All patients received the same type of chemotherapy. The median overall survival was 28 months. There was no significant difference in the clinical outcome of patients with TCC compared with that of patients with serous carcinomas. These data suggest that TCC does not confer a favorable prognosis or better response rate to chemotherapy. C1 NCI,PATHOL LAB,NATL INST HLTH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NR 12 TC 18 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1996 VL 27 IS 12 BP 1267 EP 1272 DI 10.1016/S0046-8177(96)90335-4 PG 6 WC Pathology SC Pathology GA VX746 UT WOS:A1996VX74600005 PM 8958296 ER PT J AU Shibahara, H Shigeta, M Inoue, M Hasegawa, A Koyama, K Alexander, NJ Isojima, S AF Shibahara, H Shigeta, M Inoue, M Hasegawa, A Koyama, K Alexander, NJ Isojima, S TI Diversity of the blocking effects of antisperm antibodies on fertilization in human and mouse SO HUMAN REPRODUCTION LA English DT Article DE antisperm antibody; hemizona assay; monoclonal antibody; sperm penetration assay; zona penetration assay ID SPERM-IMMOBILIZING ANTIBODIES; PELLUCIDA TIGHT-BINDING; HUMAN SEMINAL PLASMA; HEMIZONA ASSAY HZA; HUMAN-SPERMATOZOA; ZONA-PELLUCIDA; MONOCLONAL-ANTIBODY; INVITRO; SERA; INHIBITION AB The blocking effects of complement-dependent sperm immobilizing antibodies in the sera of infertile women and monoclonal antisperm antibodies against humans and mice on fertilization were investigated. The hemizona assay (HZA) and sperm penetration assay (SPA) were used to study the inhibitory effects of sera from 22 infertile patients positive for sperm immobilizing antibodies. Use of these tests allowed us to differentiate whether the antibody blocked sperm-zona pellucida tight binding and/or sperm penetration into the ooplasm. The zona pellucida penetration assay (ZPA) was also used to study the effects of four monoclonal antibodies (mAbs) on human sperm penetration into the zona pellucida. Seven mAbs against murine spermatozoa were tested for their inhibitory effects on in vitro fertilization (IVF) and HZA in mice. Of 22 patient sera with sperm immobilizing antibodies, 21 (95.5%) inhibited HZA attachment and penetration, whereas this did not occur in any of 13 patient sera without these antibodies. However, 19 of 22 (86.4%) patient sera with sperm immobilizing antibodies and eight of 13 (61.5%) patient sera without these antibodies inhibited the SPA. Two (2C6, 1G12) of four mAbs against human spermatozoa showed strong inhibitory effects in all the assays (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZA but blocked ZPA and SPA. Another mAb (H6-3C4) seemed to have no inhibitory effects on fertilization. Two (Vx 5 and Vx 8) of seven mAbs against murine spermatozoa inhibited IVF in mice but did not block mouse HZA. These findings suggest that antisperm antibodies block fertilization at specific stages, Some of them may inhibit sperm capacitation and thus prevent all processes of fertilization that follow. Some other antibodies may not affect capacitation and sperm binding to zona pellucida but inhibit the acrosome reaction, followed by the blocking of sperm penetration through zona pellucida and ooplasm. C1 HYOGO MED UNIV,DEPT OBSTET & GYNECOL,NISHINOMIYA,HYOGO 663,JAPAN. NICHHD,POPULAT RES CTR,BETHESDA,MD 20892. FUCHU HOSP,ADV FERTIL CTR,IZUMI,OSAKA,JAPAN. NR 30 TC 20 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 1996 VL 11 IS 12 BP 2595 EP 2599 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WE399 UT WOS:A1996WE39900009 PM 9021357 ER PT J AU Gandjbakhche, AH Gannot, I AF Gandjbakhche, AH Gannot, I TI Quantitative fluorescent imaging of specific markers of diseased tissue SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article ID OPTICAL-PROPERTIES; TURBID MEDIA; MODEL AB We have developed a random walk theory to relate observable fluorescent intensities on tissue surfaces to the presence of several embedded fluorescent masses. This work is an extension of analysis previously carried out for an isolated fluorescent site, Results depend on the optical properties of tissue at the excitation and emission wavelengths, as well as on the location of fluorescent targets and positions of source and detector. Measurements on tissue-like phantoms were performed to test the theory, Analysis of fluorescent signals, performed in accordance with the theory, yields accurate information about the location of the targets. Prospects of a noninvasive quantitative fluorescent imaging system, to diagnose and monitor salivary glands disease, is presented. C1 US FDA, CTR DEVICES & RADIOL HLTH, ELECTROOPT BRANCH, ROCKVILLE, MD 20857 USA. RP Gandjbakhche, AH (reprint author), NICHHD, PHYS SCI LAB, DIV COMP RES & TECHNOL, NIH, BETHESDA, MD 20892 USA. NR 27 TC 11 Z9 11 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD DEC PY 1996 VL 2 IS 4 BP 914 EP 921 DI 10.1109/2944.577316 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA XD616 UT WOS:A1996XD61600016 ER PT J AU Oakes, SA Candotti, F Johnston, JA Chen, YQ Ryan, JJ Taylor, N Liu, XW Hennighausen, L Notarangelo, LD Paul, WE Blaese, RM OShea, JJ AF Oakes, SA Candotti, F Johnston, JA Chen, YQ Ryan, JJ Taylor, N Liu, XW Hennighausen, L Notarangelo, LD Paul, WE Blaese, RM OShea, JJ TI Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3-dependent and independent pathways SO IMMUNITY LA English DT Article ID RECEPTOR-GAMMA-CHAIN; JAK-3 JANUS KINASE; B-CELLS; TYROSINE PHOSPHORYLATION; FUNCTIONAL COMPONENT; MYELOID CELLS; BETA-CHAIN; INTERLEUKIN-2; ACTIVATION; INSULIN AB Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3. Although JAK3 is required for proper lymphoid development, the precise roles of this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined. Here, we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3. Although IL-2-induced phosphorylation of IL-2R beta, JAK1, and STAT5 all required the presence of JAK3, IL-4-mediated phosphorylation of JAK1, STAT6, and insulin receptor substrates 1 and 2 did not. However, IL-4-induced effects were clearly improved following JAK3 expression. These data indicate that IL-4 signaling occurs in the absence of of JAK3, but is comparatively inefficient. These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic effects of IL-4. C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NIH,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. CHILDRENS HOSP LOS ANGELES,DIV RES IMMUNOL & BONE MARROW TRANSPLANTAT,LOS ANGELES,CA 90027. UNIV BRESCIA,DEPT PEDIAT,I-25123 BRESCIA,ITALY. NIAMSD,NIH,ARTHRIT & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892. RI Taylor, Naomi/H-4016-2014; Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU Telethon [A.042] NR 52 TC 101 Z9 102 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1996 VL 5 IS 6 BP 605 EP 615 DI 10.1016/S1074-7613(00)80274-5 PG 11 WC Immunology SC Immunology GA WA651 UT WOS:A1996WA65100010 PM 8986719 ER PT J AU Mehendale, SM Shepherd, ME Divekar, AD Gangakhedkar, RR Kamble, SS Menon, PA Yadav, R Risbud, AR Paranjape, RS Gadkari, DA Quinn, TC Bollinger, RC Rodrigues, JJ AF Mehendale, SM Shepherd, ME Divekar, AD Gangakhedkar, RR Kamble, SS Menon, PA Yadav, R Risbud, AR Paranjape, RS Gadkari, DA Quinn, TC Bollinger, RC Rodrigues, JJ TI Evidence for high prevalence & rapid transmission of HIV among individuals attending STD clinics in Pune, India SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Article DE behavioural factors, biological factors, cohort; female sex workers; HIV infection, incidence, prevalence risk behaviour, STD ID SEXUALLY-TRANSMITTED DISEASES; IMMUNODEFICIENCY-VIRUS INFECTION; RISK-FACTORS; NORTHERN THAILAND; AIDS EPIDEMIC; SEX WORKERS; PROSTITUTES; IMPACT; COHORT AB Prevalence and incidence of HIV-1 infection among persons attending two STD clinics in Pune between May 1993 and October 1995 are reported. On screening 5321 persons, the overall prevalence of HIV-1 infection was found to be 21.2 per cent, being higher in females (32.3%) than in males (19.3%). Analysis of behavioural;and biological factors showed that old age, sex work, lifetime number of sexual partners, receptive anal sex, lack of circumcision, genital diseases and lack of formal education were related to a higher HIV-1 seroprevalence. The observed incidence rate of 10.2 per cent per year was very high, much higher in women than in men (14.2% and 9.5% per year respectively) and over three times higher among the sex workers. Females in sex work, males having recent contacts with female sex workers (FSWs) and living away from the family and persons with previous or present genital diseases had a higher risk of seroconversion. Condom usage was shown to have a protective effect in seroprevalence and seroincidence analysis. With limited available resources and lack of a suitable vaccine or a drug, long-term prevention policy of creating awareness in the community must be supplemented by strengthening STD control measures and promotion of condom use and safe sex. Factors related to availability and utilization of condoms must be carefully investigated. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. NIAID,NIH,BETHESDA,MD 20892. RP Mehendale, SM (reprint author), NATL AIDS RES INST,73 G BLOCK,MIDC,POST BOX 1895,PUNE 411026,MAHARASHTRA,INDIA. NR 26 TC 61 Z9 63 U1 1 U2 1 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4508 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD DEC PY 1996 VL 104 BP 327 EP 335 PG 9 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA WB319 UT WOS:A1996WB31900001 PM 8996932 ER PT J AU Hann, DM Osofsky, JD Culp, AM AF Hann, DM Osofsky, JD Culp, AM TI Relating the adolescent mother-child relationship to preschool outcomes SO INFANT MENTAL HEALTH JOURNAL LA English DT Article ID TEENAGE; INTERVENTION; INFANTS AB Two domains of potential risk in relation to the cognitive-linguistic outcomes of preschool children of adolescent mothers were investigated: (1) interactive features of the mother-child relationship and (2) aspects of the demographic context of parenting. Sixty-nine adolescent mothers and their children participated in evaluations when the children were 13, 20, 30, and 44 months old. Results indicated that the cognitive-linguistic development of children of adolescent mothers was affected by both the mother-child relationship and cumulative index of demographic risk. Specifically, positive maternal affect, mother-child verbal reciprocity, mother-child interactive fit, and cumulative demographic risk all contributed to explaining difficulties in preschool cognitive and linguistic functioning in children of adolescent mothers. C1 LOUISIANA STATE UNIV,MED CTR,BATON ROUGE,LA 70803. OKLAHOMA STATE UNIV,STILLWATER,OK 74078. RP Hann, DM (reprint author), NIMH,ROOM 11C-16,5600 FISHERS LANE,ROCKVILLE,MD 20858, USA. NR 15 TC 28 Z9 30 U1 0 U2 0 PU MICHIGAN ASSN INFANT MENTAL HEALTH PI E LANSING PA MICHIGAN STATE UNIV DEPT PSYCHOLOGY, E LANSING, MI 48824-1117 SN 0163-9641 J9 INF MENTAL HLTH J JI Infant Ment. Health J. PD WIN PY 1996 VL 17 IS 4 BP 302 EP 309 DI 10.1002/(SICI)1097-0355(199624)17:4<302::AID-IMHJ2>3.0.CO;2-O PG 8 WC Psychology, Developmental SC Psychology GA VX152 UT WOS:A1996VX15200002 ER PT J AU Elson, LH Days, A Calvopina, M Paredes, W Araujo, E Guderian, RH Bradley, JE Nutman, TB AF Elson, LH Days, A Calvopina, M Paredes, W Araujo, E Guderian, RH Bradley, JE Nutman, TB TI In utero exposure to Onchocerca volvulus: Relationship to subsequent infection intensity and cellular immune responsiveness SO INFECTION AND IMMUNITY LA English DT Article ID ANTIGEN; MICROFILARIAE; SENSITIZATION; SUPPRESSION; RESPONSES; CHILDREN; INUTERO; MOTHERS; ECUADOR AB Afro-Ecuadorian individuals from an area where Onchocerca volvulus is hyperendemic have been monitored for infection over the past 16 years, To determine whether in utero exposure to O. volvulus biases a child's subsequent immune responses, children (9 to 16 years old) for whom the mother's infection status was known were chosen for study. Children of infected mothers (n = 19) had significantly higher levels of skin microfilariae than children of uninfected mothers (n = 13; P = 0.021). While the serum levels of O. volvulus-specific immunoglobulin G (IgG), IgG subclasses, and IgE showed no significant differences between the two groups of children, peripheral blood mononuclear cells of children of infected mothers produced higher levels of Th2-type cytokines to several parasite antigens and lower levels of Th1-type cytokines to nonparasite antigens than those of children of uninfected mothers. Thus, in utero exposure to O. volvulus has a long-term effect on the child's subsequent cellular immune response that mag render the child more susceptible to O. volvulus infection postnatally. C1 NIAID,PARASIT DIS LAB,NATL INST HLTH,BETHESDA,MD 20892. HOSP VOZANDES,INVEST CLIN,QUITO,ECUADOR. UNIV SALFORD,DEPT BIOL SCI,SALFORD M5 4WT,LANCS,ENGLAND. OI Bradley, Janette/0000-0003-3973-7977 NR 23 TC 41 Z9 41 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1996 VL 64 IS 12 BP 5061 EP 5065 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VU635 UT WOS:A1996VU63500026 PM 8945547 ER PT J AU Petter, R KwonChung, KJ AF Petter, R KwonChung, KJ TI Disruption of the SNF1 gene abolishes trehalose utilization in the pathogenic yeast Candida glabrata SO INFECTION AND IMMUNITY LA English DT Article ID SACCHAROMYCES-CEREVISIAE SNF1; ACTIVATED PROTEIN-KINASE; GLUCOSE REPRESSION; CARBON METABOLISM; ENCODING GENE; EXPRESSION; CLONING; TRANSFORMATION; DELETION; HOMOLOG AB The SNF1 gene product, a serine/threonine protein kinase, is a global regulatory protein which has been isolated from several organisms, In Saccharomgces cerevisiae the SNF1 gene product is essential for the derepression of glucose repression since snf1 strains are unable to utilize sucrose, galactose, maltose, melibiose, or nonfermentable carbohydrates. Moreover, the SNF1 gene product was suggested to interact with additional regulatory pathways and to affect the expression of multiple target genes as reflected by the pleiotropic nature of the snf1 mutation. Here,ve report the characterization of the SNF1 homolog of Candida glabrata, a pathogenic yeast phylogenetically related to S. cerevisiae, The carbon utilization spectrum of C. glabrata is considerably narrower than that of other pathogenic yeasts, and the majority of the strains utilize solely glucose and trehalose from among 20 of the most commonly tested carbohydrates. Disruption of the C. glabrata SNF1 homolog resulted in the loss of the ability to utilize trehalose, indicating that even in an organism With such a limited carbon utilization spectrum, the regulatory mechanism governing catabolic repression is preserved. C1 NIAID,MOL MICROBIOL SECT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NR 35 TC 17 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1996 VL 64 IS 12 BP 5269 EP 5273 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VU635 UT WOS:A1996VU63500055 PM 8945576 ER PT J AU Scidmore, MA Rockey, DD Fischer, ER Heinzen, RA Hackstadt, T AF Scidmore, MA Rockey, DD Fischer, ER Heinzen, RA Hackstadt, T TI Vesicular interactions of the Chlamydia trachomatis inclusion are determined by Chlamydial early protein synthesis rather than route of entry SO INFECTION AND IMMUNITY LA English DT Article ID PHAGOSOME-LYSOSOME FUSION; CULTURED MACROPHAGES; TOXOPLASMA-GONDII; MYCOBACTERIUM-TUBERCULOSIS; PHAGOLYSOSOME FUSION; POLYANIONIC AGENTS; INFECTED-CELLS; HELA-CELLS; PSITTACI; MEMBRANE AB Chlamydiae replicate intracellularly within a vacuole that has recently been characterized as intersecting an exocytic pathway, One of the initial events during chlamydial infection is the expression of a chlamydial early gene product(s) that effectively isolates the inclusion from the endocytic-lysosomal pathway and makes it fusogenic with sphingomgelin-containing exocytic vesicles. Associated with this change in vesicular interaction is the delivery of the vacuole to the peri-Golgi region of the host cell, Inhibition of chlamydial early transcription or translation causes Chlamydia trachomatis-containing vesicles to remain dispersed throughout the cytoplasm, where they eventually fuse with lysosomes. Chlamydiae that have been internalized by Fc-mediated endocytosis also avoid lysosomal digestion by a mechanism that requires chlamydial protein synthesis. These results suggest that the vesicular interactions of the chlamydial inclusion are defined by parasite-directed modification of the endocytic vesicle rather than by the route of internalization. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HOSP PARASITE INTERACT SECT,HAMILTON,MT 59840. NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. FU NICHD NIH HHS [N01-HD-2-3144] NR 38 TC 113 Z9 113 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1996 VL 64 IS 12 BP 5366 EP 5372 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VU635 UT WOS:A1996VU63500068 PM 8945589 ER PT J AU Ruhl, S Sandberg, AL Cole, MF Cisar, JO AF Ruhl, S Sandberg, AL Cole, MF Cisar, JO TI Recognition of immunoglobulin A1 by oral Actinomyces and streptococcal lectins SO INFECTION AND IMMUNITY LA English DT Article ID SALIVARY-BACTERIAL INTERACTIONS; LINKED OLIGOSACCHARIDE UNITS; CARBOHYDRATE UNITS; IGA1 IMMUNOGLOBULIN; VISCOSUS T14V; HINGE REGION; SIALIC-ACID; SANGUIS; SPECIFICITY; ADHERENCE AB Actinomyces naeslundii and Streptococcus gordonii, oral bacteria that possess Gal/GaINAc- and sialic acid-reactive lectins, respectively, were adherent to immobilized secretory immunoglobulin A (IgA) and two IgA1 myeloma proteins but not to two IgA2 myeloma proteins. Apparently, O-linked oligosaccharides at the hinge region of the IgA1 heavy chain are receptors for lectin-mediated adhesion of these bacteria. C1 NIDR,NIH,MICROBIAL ECOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. FU NIDCR NIH HHS [DE08178] NR 42 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1996 VL 64 IS 12 BP 5421 EP 5424 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VU635 UT WOS:A1996VU63500079 PM 8945600 ER PT J AU Chanock, SJ Pizzo, PA AF Chanock, SJ Pizzo, PA TI Fever in the neutropenic host SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; FEBRILE GRANULOCYTOPENIC PATIENTS; INVASIVE FUNGAL-INFECTIONS; PLACEBO-CONTROLLED TRIAL; LOW-RISK NEUTROPENIA; TERM FOLLOW-UP; CANCER-PATIENTS; DOUBLE-BLIND; RANDOMIZED TRIAL AB Fever in the neutropenic patient following myelosuppressive chemotherapy is a medical emergency. Appropriate antimicrobial therapy can dramatically reduce infection-related morbidity and mortality. This article reviews the rationale and methodology of treatment as well as its applicability to other neutropenic states. The utility of adjunct therapy with granulocyte- stimulating compounds is also discussed. RP Chanock, SJ (reprint author), NCI,INFECT DIS SECT,PEDIAT BRANCH,NIH,BLDG 10,RM 13N240,BETHESDA,MD 20892, USA. NR 115 TC 17 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1996 VL 10 IS 4 BP 777 EP & DI 10.1016/S0891-5520(05)70326-3 PG 21 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VX665 UT WOS:A1996VX66500006 PM 8958168 ER PT J AU Ibanes, JD Leininger, JR Jarabek, AM Harkema, JR Hotchkiss, JA Morgan, KT AF Ibanes, JD Leininger, JR Jarabek, AM Harkema, JR Hotchkiss, JA Morgan, KT TI Reexamination of respiratory tract responses in rats, mice, and rhesus monkeys chronically exposed to inhaled chlorine SO INHALATION TOXICOLOGY LA English DT Article ID F344 RATS; QUANTITATIVE HISTOCHEMISTRY; EPITHELIAL MUCOSUBSTANCES; INHALATION EXPOSURE; B6C3F1 MICE; NASAL; TOXICITY; LESIONS; OZONE; DIMETHYLAMINE AB Important data for human risk assessment of inhaled chlorine are provided by a recent rodent cancer bioassay (Wolf et al., 1995) and a chronic inhalation toxicity study in rhesus monkeys (Klonne et al., 1987), To improve interspecies comparisons based upon these data sets, the tissues from these studies were reexamined to (a) map the location of responses to assess the potential role of local chlorine dosimetry, (b) generate quantitative data on selected endpoints to compliment subjective scores, and (c) further characterize the responses in relation to interspecies differences and potential human health risks. Chlorine-induced lesions, which were confined to the respiratory tract, exhibited both similarities and differences among rodents and primates. At equivalent airborne concentrations (similar to 2.5 ppm), chlorine-induced responses were less severe in rhesus monkeys, but extended more distally in the respiratory tract to involve the trachea, while treatment-induced lesions were confined to the nose in rats and mice. Quantitation of septal fenestration, intraepithelial mucus, intraepithelial eosinophilic material, eosinophil infiltration (detected during the present study), and olfactory sensory cell loss generally supported previously reported subjective pathology scores and clarified concentration-response relationships. In both rodents and rhesus monkeys, airflow-driven regional dosimetry patterns were considered to play a major role in lesion distribution. The present work highlights the need for understanding regional respiratory-tract dosimetry and mechanisms of tissue response for inhaled chlorine in laboratory animals and humans. C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. US EPA,NATL CTR ENVIRONM ASSESSMENT,RES TRIANGLE PK,NC 27711. MICHIGAN STATE UNIV,DEPT PATHOL,E LANSING,MI 48824. NR 48 TC 5 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD DEC PY 1996 VL 8 IS 9 BP 859 EP 876 DI 10.3109/08958379609034268 PG 18 WC Toxicology SC Toxicology GA VZ087 UT WOS:A1996VZ08700002 ER PT J AU Raziuddin, A Longo, DL Mason, L Ortaldo, JR Murphy, WJ AF Raziuddin, A Longo, DL Mason, L Ortaldo, JR Murphy, WJ TI Ly-49 G2(+) NK cells are responsible for mediating the rejection of H-2(b) bone marrow allografts in mice SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE bone marrow; hybrid resistance; Ly-49 subset; NK cell; transplantation ID NATURAL-KILLER-CELLS; T-CELLS; ADHESION; BIOLOGY; SUBSETS; GRAFTS AB NK cells can mediate the specific rejection of bone marrow but not solid tissue allografts in lethally irradiated mice. NK cells are also responsible for the phenomenon of 'hybrid resistance' in which F-1 hybrid H-2 heterozygous mice can reject parental H-2 homozygous bone marrow grafts, Ly-49C and Ly-49 G2 are markers identified on subsets of NK cells. While Ly-49C(+) NK cells have been demonstrated to mediate the specific rejection of H-2(d) bone marrow allografts, the role of the Ly-49 G2(+) NK subset is unclear because depletion of this subset in vivo did not affect splenic NK activity against tumor targets. Through bone marrow transplantation typing studies, we demonstrate that Ly-49 G2(+) NK cells complement Ly-49C(+) NK cells in that they specifically mediate the rejection of H-2(b) bone marrow allografts in lethally irradiated mice. In support of this, depletion of the Ly-49C(+) NK subset in vivo also enhanced the ability of the mice to reject H-2(b) bone marrow cells suggesting that the depletion was augmenting the ability of the Ly-49 G2(+) NK cells to reject the marrow allografts, Depletion of Ly-49 G2(+) NK cells in F-1 hybrid mice abrogated their ability to reject parental H-2(b) but not H-2(d) bone marrow grafts, Therefore, Ly-49 G2 denotes a subset of NK cells that appears to play a critical role in the recognition of H-2(b) bone marrow cells in allogeneic and F-1 hybrid mice. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 21 TC 33 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 1996 VL 8 IS 12 BP 1833 EP 1839 DI 10.1093/intimm/8.12.1833 PG 7 WC Immunology SC Immunology GA WA313 UT WOS:A1996WA31300002 PM 8982767 ER PT J AU Garraud, O Nkenfou, C Bradley, JE Nutman, TB AF Garraud, O Nkenfou, C Bradley, JE Nutman, TB TI Differential regulation of antigen-specific IgG4 and IgE antibodies in response to recombinant filarial proteins SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anti-CD40; B cells; filarial; IgE; IgG4; isotypes ID HUMAN-B-LYMPHOCYTES; T-CELL CLONES; IFN-GAMMA; MONOCLONAL-ANTIBODIES; INVITRO SYNTHESIS; CROSS-LINKING; PROLIFERATION; IL-4; CD23; INTERLEUKIN-4 AB Having identified two recombinant filarial proteins (Ov27 and OvD5B) that induced patient peripheral blood mononuclear cells to produce antigen-specific IgG4/IgE antibodies in vitro, we assessed the role these filarial antigens play in inducing antigen-specific isotype switching (gamma 4 and epsilon) in the absence of T cells. Purified CD19(+) s gamma(-)/s epsilon(-) B cells were cultured with either of these antigens in the presence of anti-CD40 mAb and human IL-4. Both antigen and polyclonal signals delivered by IL-4 (or IL-13) were necessary for the induction of specific IgG4/IgE antibodies. To assess the role played by cytokines produced by B lymphocytes in antigen-driven selection of the gamma 4 or epsilon isotype, neutralizing anti-cytokine antibodies were used in vitro. While anti-IL-12 antibodies did not alter the antigen-specific IgG4/IgE production, anti-IL-6, anti-IL-13 and anti-tumor necrosis factor-alpha antibodies significantly inhibited the production of IgG4/IgE. Anti-IL-P and anti-IL-10 antibodies appeared to down-regulate antigen-specific IgG4 antibodies without affecting antigen-specific IgE antibodies. Although anti-CD21 antibodies had no effect on specific IgE antibodies, they up-regulated specific lgG4 antibodies, a finding paralleled by anti-CD23 antibodies. These data suggest that certain filarial antigen-specific IgG4/IgE responses can be differentially regulated and that certain endogenously produced molecules from B cells - such as IL-2, ii-in, CD23 and CD21 - play a significant role in the induction of specific isotypes of antigen-specific antibodies. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NEW ENGLAND BIOLABS INC,BEVERLY,MA 01915. UNIV SALFORD,SALFORD M5 4WT,LANCS,ENGLAND. OI Bradley, Janette/0000-0003-3973-7977 NR 49 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 1996 VL 8 IS 12 BP 1841 EP 1848 DI 10.1093/intimm/8.12.1841 PG 8 WC Immunology SC Immunology GA WA313 UT WOS:A1996WA31300003 PM 8982768 ER PT J AU Scholmerich, A vanAken, MAG AF Scholmerich, A vanAken, MAG TI Attachment security and maternal concepts of ideal children in Northern and Southern Germany SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID STRANGE-SITUATION; INFANT ATTACHMENT; Q-SORT; Q-SET; MOTHERS; FATHER; BEHAVIOR; ORGANIZATION; SENSITIVITY; QUALITY AB The degree of attachment security and the concept of an ''ideal child'' were investigated by asking 83 mothers to describe the secure-base behaviour of either their own children or of an imagined ''ideal child'' using a German translation of Waters' (1987) Attachment Q-Set. Additionally, II German experts generated a ''maximally secure'' criterion sort, which was virtually identical with the established US criterion sort. Attachment security is highly desirable, as shown by the similarity between the profiles of the ideal descriptions and the security criterion sort. Two subsamples from Northern and Southern Germany showed similar intercorrelations of Attachment Q-Set subscales. We identified small differences in Northern and Southern mothers' perceptions of an ''ideal'' child in items relating to activity and independence. However, Northern and Southern mothers' descriptions of their toddlers did not differ in attachment security or dependence. C1 MAX PLANCK INST PSYCHOL RES, D-80804 MUNICH, GERMANY. RP Scholmerich, A (reprint author), NICHHD, SSED, BSA BLDG 331, 9190 ROCKVILLE PIKE, BETHESDA, MD 20814 USA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 40 TC 4 Z9 4 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD DEC PY 1996 VL 19 IS 4 BP 725 EP 738 PG 14 WC Psychology, Developmental SC Psychology GA VW726 UT WOS:A1996VW72600003 ER PT J AU Palm, L Burka, LT Hojrup, P Stevens, RD Tomer, KB AF Palm, L Burka, LT Hojrup, P Stevens, RD Tomer, KB TI Identification of five hemoglobins in B6C3F1 mice by mass spectrometry and sequence analysis SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHIC SEPARATION; BETA-GLOBIN GENES; RAT HEMOGLOBIN; CHAINS; EVOLUTION; PROTEINS AB The aim of the work is to identify and characterize the hemoglobins found in B6C3F1 mice using mass spectrometry. The primary structures are compared to those reported for BALB/c mice. Individual hemoglobin chains were isolated by reversed-phase high performance liquid chromatography (RP-HPLC). The molecular masses of the globins were determined using electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). The purified globin chains mere enzymatically cleaved and the resulting peptides were separated by RP-HPLC. The chains were identified by N-terminal sequencing and mass spectrometry (MALDI). Selected peptides were analysed by Edman degradation. ESI analysis indicates that B6C3F1 mice have two alpha-globin chains (alpha-1 and alpha-2) and at least three beta-globin chains, beta-1, beta-2 and beta-3. This is one additional alpha- and one additional beta-globin chain than reported in the literature for BALB/c mice. Mass and sequence analysis of enzymatically generated peptides showed variations in the amino acid sequence in the alpha-1, alpha-2, beta-2 and beta-3 chains compared to the BALB/c mouse hemoglobins (alpha, beta(minor) and beta(major)). The study showed that mass spectrometry in combination with traditional protein chemistry is able to identify and locate minor protein sequence variations. Copyright (C) 1996 Elsevier Science Ltd C1 NIEHS,RES TRIANGLE PK,NC 27709. ODENSE UNIV,DEPT MOL BIOL,DK-5230 ODENSE M,DENMARK. DUKE UNIV,MED CTR,MASS SPECTROMETRU FACIL,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 17 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD DEC PY 1996 VL 28 IS 12 BP 1319 EP 1326 DI 10.1016/S1357-2725(96)00090-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE173 UT WOS:A1996WE17300004 PM 9022290 ER PT J AU Lee, SK Krebsbach, PH Matsuki, Y Nanci, A Yamada, KM Yamada, Y AF Lee, SK Krebsbach, PH Matsuki, Y Nanci, A Yamada, KM Yamada, Y TI Ameloblastin expression in rat incisors and human tooth germs SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE ameloblastin; amelogenesis; enamel protein; tooth ID DEVELOPING BOVINE ENAMEL; MOUSE MOLAR TOOTH; MATRIX PROTEINS; PARTIAL SEQUENCES; GENE-EXPRESSION; AMELOGENIN; FETAL; PURIFICATION; TUFTELIN; INVITRO AB We recently identified ameloblastin as an ameloblast-specific gene product from a rat incisor cDNA library (Krebsbach et al., J. Biol. Chem. 271: 4431-4435, 1996). Here we report the developmental pattern of expression of ameloblastin in rat incisors and human tooth germs as visualized by in situ hybridization and immunochemistry. Compared to the expression of amelogenin, the major ameloblast product, ameloblastin mRNA was more widely expressed in ameloblasts from the presecretory to the late maturation stage of development. Am eloblastin mRNA was first observed in the juxtanuclear cytoplasm of presecretory stage ameloblasts, gradually increased in the distal cytoplasm of secretory stage ameloblasts and was found throughout the cytoplasm of early to late maturation stage ameloblasts. The immunostaining of ameloblastin, using a monospecific antibody raised against a recombinant protein, showed intense reactivity in Tomes' processes of secretory stage ameloblasts and surrounding enamel. The immunoreaction was concentrated in the juxtanuclear cytoplasm of late maturation stage ameloblasts. High-resolution colloidal gold Immunocytochemistry established the presence of ameloblastin antigenicity in the Golgi apparatus, secretory granules in Tomes' process and enamel. Human tooth germs in early to late bell stage also expressed ameloblastin mRNA and ameloblastin antigenicity in the ameloblasts. Western blot analysis of protein extracts from rat incisor tissues indicated that ameloblastin can be found in the enamel epithelial tissue and in mineralized enamel, as well as in the EDTA decalcification solution. These data indicate that ameloblastin is an ameloblast secretory product which is sequentially expressed from the presecretory to the late maturation stage in rat and human teeth. This unique developmental pattern suggests that ameloblastin may have a broader role in amelogenesis than amelogenin and tuftelin. C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MONTREAL,FAC DENT,DEPT STOMATOL,MONTREAL,PQ,CANADA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 44 TC 57 Z9 63 U1 1 U2 3 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD DEC PY 1996 VL 40 IS 6 BP 1141 EP 1150 PG 10 WC Developmental Biology SC Developmental Biology GA WC128 UT WOS:A1996WC12800008 PM 9032019 ER PT J AU Bird, HR Andrews, H SchwabStone, M Goodman, S Dulcan, M Richters, J RubioStipec, M Moore, RE Chiang, PH Hoven, C Canino, G Fisher, P Gould, MS AF Bird, HR Andrews, H SchwabStone, M Goodman, S Dulcan, M Richters, J RubioStipec, M Moore, RE Chiang, PH Hoven, C Canino, G Fisher, P Gould, MS TI Global measures of impairment for epidemiologic and clinical use with children and adolescents SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE epidemiology; impairment; assessment; measures; case definition ID ASSESSMENT SCALE; PREVALENCE; DISORDERS; COMMUNITY; DIAGNOSIS; SAMPLE; HEALTH AB Objective: Two global measures of impairment developed for the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study and their potential for epidemiologic and clinical use are assessed. The measures are a non-clinician version of the Children's Global Assessment Scale (CGAS), designed to be scored by parents or by lay interviewers, and the Columbia Impairment Scale (CIS), a 13-item scale that can be administered directly by lay or clinical interviewers to parents or youth. Method: The validity of these impairment measures is evaluated by examining their correlations with clinician CGAS scores and with other factors expected to be associated with impairment. Discriminant function analyses are also conducted to assess thresholds on each measure. Results: All versions of the CIS and the CGAS show good variability in the community and correlate significantly with other indicators of psychological dysfunction and with the clinician's CGAS score. There is evidence of good construct, discriminant, and concurrent validity. Inter-site differences are assessed and appear to be culturally determined. Suggested thresholds for each measure are provided. Conclusions: The findings support the construct and concurrent validity of these measures of impairment. The ratings provided by lay interviewers based on parent interviews, relate better to ratings provided by clinicians, than do ratings based on youth interviews or provided by parents themselves. The CIS has an advantage over the non-clinician CGAS in that its rating does not rely on clinical judgment. Both measures are useful for clinical as well as epidemiologic purposes. The findings support the integration of both symptomatology and functional impairment in child psychiatric diagnostic assessments. Limitations to these findings are discussed. C1 UNIV PUERTO RICO,SAN JUAN,PR 00936. EMORY UNIV,ATLANTA,GA 30322. NIMH,BETHESDA,MD 20892. YALE UNIV,NEW HAVEN,CT 06520. NORTHWESTERN UNIV,EVANSTON,IL 60208. COLUMBIA UNIV,NEW YORK,NY 10027. NR 25 TC 138 Z9 138 U1 7 U2 20 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1049-8931 J9 INT J METHOD PSYCH JI Int. J. Methods Psychiatr. Res. PD DEC PY 1996 VL 6 IS 4 BP 295 EP 307 DI 10.1002/(SICI)1234-988X(199612)6:4<295::AID-MPR173>3.3.CO;2-5 PG 13 WC Psychiatry SC Psychiatry GA WJ999 UT WOS:A1996WJ99900011 ER PT J AU Budillon, A Clair, T Hartman, N Strong, J Sobukawa, Y Miki, K Worby, A Murray, KJ ChoChung, YS AF Budillon, A Clair, T Hartman, N Strong, J Sobukawa, Y Miki, K Worby, A Murray, KJ ChoChung, YS TI Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cAMP; protein kinase A; serum factors; phosphodiesterase ID HL-60 LEUKEMIA-CELLS; SELECTIVE CAMP ANALOGS; CHINESE-HAMSTER OVARY; CYCLIC-AMP ANALOGS; 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE; ADENOSINE METABOLITE; 8-CHLORO-CYCLIC AMP; DOWN-REGULATION; MOLT-4 CELLS; CANCER AB 8-Chloro-cyclic AMP (8-Cl-cAMP) exhibits growth inhibition in vitro and in vivo in a broad spectrum of cancer cell lines. We examined whether the hydrolyzed metabolite is involved in the effect of 8-Cl-cAMP. 8-Cl-cAMP (5 mu M, 3 days) exerted varying degrees (0-51%) of growth inhibition on the same cell line cultured in the medium containing different heat-inactivated serum. HPLC analysis neither detected 8-Cl-adenosine in the medium nor demonstrated any correlation between the decrease in 8-Cl-cAMP concentration in the medium and the degree of growth inhibition. The low K-m phosphodiesterase activity in the sera did not correlate with the varying degrees of growth inhibition. The cAMP-dependent protein kinase RI(alpha) subunit expression in the same cell line varied widely with the different serum supplements. 8-Cl-CAMP-, but not 8-Cl-adenosine-induced, growth inhibition correlated with the basal levels of RI(alpha) and specific downregulation of RI(alpha). 8-Cl-cAMP, but not 8-Cl-phenyl-thio-cAMP or N-6-benzyl-cAMP, inhibited cell growth in serum-free medium. These results show that 8-Cl-cAMP induces growth inhibition through down-regulation of protein kinase A type I in the absence of its hydrolysis. C1 NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. US FDA,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. TERUMO CO LTD,KANAGAWA,JAPAN. SMITH KLINE BEECHAM PHARMACEUT,WELWYN GARDEN CIT,HERTS,ENGLAND. OI Budillon, Alfredo/0000-0002-6330-6053 NR 26 TC 1 Z9 1 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 DEC PY 1996 VL 9 IS 6 BP 1113 EP 1120 PG 8 WC Oncology SC Oncology GA VU549 UT WOS:A1996VU54900004 PM 21541619 ER PT J AU Sedlacek, HH Czech, J Naik, R Kaur, G Worland, P Losiewicz, M Parker, B Carlson, B Smith, A Senderowicz, A Sausville, E AF Sedlacek, HH Czech, J Naik, R Kaur, G Worland, P Losiewicz, M Parker, B Carlson, B Smith, A Senderowicz, A Sausville, E TI Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Review DE cyclin-dependent kinase; inhibitor; tumor therapy; preclinical activity; toxicity; pharmacokinetic; Flavopiridol ID FLAVONE ACETIC-ACID; CELL-CYCLE PROGRESSION; HAMSTER OVARY CELLS; MURINE RENAL-CANCER; PROTEIN-KINASES; CDC2 KINASE; ANTITUMOR-ACTIVITY; MAMMALIAN-CELLS; P34CDC2 KINASE; FLAVONE-8-ACETIC ACID AB Flavopiridol is a new synthetic flavone, structurally related to a natural alkaloid, originally purified from Dysoxylum binectariferum, a plant indigenous to India and used in Indian folk medicine. Flavopiridol was detected by a tandem screening system consisting in inhibition of the EGF-receptor Tyrosine phosphokinase and cytotoxicity. As a cytostatic mechanism, however, Flavopiridol strongly inhibits the cyclin-dependent kinases (cdk1, cdk2, cdk4, cdk7), with the potential to cause inhibition of cell cycle progression in G(1) and G(2) by multiple mechanisms relatable to cdk inhibition. In certain cell types, Flavopiridol induces apoptosis. The antitumor activity of that compound on human xenograft tumors is similar to standard cytostatic drugs and superior to them at least in prostate carcinoma. The dose limiting toxicity is diarrhea. Compared with other flavonoids or other kinase inhibitors Flavopiridol can be regarded as unique as no other compound is yet known that as specifically and potently inhibits nearly all the main cyclin dependent kinases and by that mechanisms can arrest cell cycle progression in G(1) as well as in G(2) and no other specific kinase inhibitor is known, which after i.v. or oral application reduces the growth of subcutaneous or subrenal xenografts of human tumors of different types. Initial results of a phase I study at the National Cancer Institute (NCI), USA, (Investigational New Drug Application no. 46211) provided some clinical and laboratory evidence for antineoplastic effect at nontoxic doses (no grade IV toxicities encountered). Thus, Flavopiridol is clearly in need of further clinical evaluation of its tumor therapeutic potential. In this review the chemical profile, tumorpharmacology (in vitro activity, inhibition of cdk's and preclinical in vivo activity), preclinical toxicology and pharmacokinetic of Flavopiridol are reviewed to provide a comprehensive source to aid further developmental efforts. C1 HOECHST MARION ROUSSEL LTD,CTR BASIC RES,MUMBAI 400080,INDIA. NCI,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD. RP Sedlacek, HH (reprint author), BEHRINGWERKE AG,D-35041 MARBURG,GERMANY. NR 135 TC 214 Z9 216 U1 0 U2 12 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 DEC PY 1996 VL 9 IS 6 BP 1143 EP 1168 PG 26 WC Oncology SC Oncology GA VU549 UT WOS:A1996VU54900008 PM 21541623 ER PT J AU Wang, J Wei, SJ Yang, WK Lin, WC Yang, DM WhangPeng, J Ting, CC AF Wang, J Wei, SJ Yang, WK Lin, WC Yang, DM WhangPeng, J Ting, CC TI In vitro and in vivo correlation of the effect of granulocytemacrophage colony-stimulating factor gene transfer on the tumorigenicity and immunogenicity of B16 melanoma SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE GM-CSF; gene transfer; tumor immunity ID LASTING ANTITUMOR IMMUNITY; ACTIVATED KILLER-CELLS; TUMOR-NECROSIS-FACTOR; IN-VIVO; REDUCED TUMORIGENICITY; MEDIATED-IMMUNITY; INTERFERON-GAMMA; LEUKEMIA-VIRUS; EXPRESSION; INVIVO AB Transduction of murine B16 melanoma cells with a GM-CSF gene, the B16-MG tumor line, showed reduced tumorigenicity. In vitro studies demonstrated no remarkable difference between the parent and transduced tumor lines in their ability to induce secondary response to generate the anti-tumor killer cells (immunogenicity), or in their susceptibility to the killing by anti-tumor killer cells (immunosensitivity). Both CD4(+) and CD8(+) cells were required for the generation of the effecters. Nevertheless the effecters were determined to be Thy1.2(+), CD8(-), and NK1.1(-). At least two antigenic specificities could be defined in the cytolytic reactions. One was a broadly cross-reactive antigen shared by a variety of tumor cells, and the other apparently a tumor-specific antigen which was only present in B16 tumors. Cold target inhibition experiment confirmed these specificities. In the in vivo tumor transplantation study, the B16-MG cell line was not only more immunogenic but also was more immunosensitive than the parent line. More than 50% of the mice which were immunized with B16-MG remained tumor free after challenge with the parent tumor B16, indicating that GM-CSF gene transfer makes an effective tumor vaccine. The in vivo protective effect was specific for B16 tumor, thus only the tumor-specific antigen could function as transplantation antigen. Both CD4(+) and CD8(+) cells were required for providing the in vivo protection. Both the B16 and B16-MG tumor bearing hosts could generate anti-tumor killer cells, hence the development of progressive growth of B16 tumor was not due to the lack of anti-tumor immune response. It appears that the overall effect of in vivo tumor immunity is determined by a complex network of interactions among different compartments of host immune cells and different compartments of host immune cells and different immune-regulatory molecules derived from the host and from the tumor. C1 NCI,DIV BASIC SCI,LAB IMMUNE CELL BIOL,NATL INST HLTH,BETHESDA,MD 20892. ACAD SINICA,INST BIOMED SCI,VET GEN HOSP,COOPERAT CANC CLIN RES LAB,TAIPEI,TAIWAN. RI Lin, Wen-chang/B-3100-2011 OI Lin, Wen-chang/0000-0003-0194-1745 NR 39 TC 4 Z9 4 U1 0 U2 1 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 DEC PY 1996 VL 9 IS 6 BP 1267 EP 1276 PG 10 WC Oncology SC Oncology GA VU549 UT WOS:A1996VU54900022 PM 21541637 ER PT J AU Whitcup, SM Chan, CC Luyo, DA Bo, P Li, Q AF Whitcup, SM Chan, CC Luyo, DA Bo, P Li, Q TI Topical cyclosporine inhibits mast cell-mediated conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE allergy; conjunctivitis; cyclosporine; inflammation; mast cell ID SIGHT-THREATENING UVEITIS; IGE; HISTAMINE; RELEASE; FK506 AB Purpose. Allergic conjunctivitis is a common condition caused by a mast cell-mediated hypersensitivity reaction to immunoglobulin E-bound allergens. The purpose of this study was to investigate the effect of topical cyclosporine A on the development of mast sell-mediated conjunctivitis in mice. Methods, Allergic conjunctivitis was induced in C57BL/6 mice by topical applications of compound 48/80, a mast cell degranulating agent. In two separate experiments, mice were treated with topical cyclosporine A (0.05%, 0.2%, or 0.4%), prednisolone acetate 1%, or phosphate-buffered saline. Twenty-four hours after compound 48/80 instillation, the number of neutrophils, eosinophils, lymphocytes, macrophages, and the number of preserved goblet cells and undegranulated mast cells in the conjunctiva were counted by a masked observer. Results. In both experiments, treatment with all three doses of cyclosporine A resulted in a statistically significant reduction in the number of infiltrating neutrophils and eosinophils compared to saline-treated controls. There was no significant difference in the treatment effect of cyclosporine and prednisolone acetate. In addition, there was increased preservation of goblet cells in the cyclosporine A-treated animals. Immunohistochemical staining showed a reduction in infiltrating lymphocytes and a smaller reduction in infiltrating macrophages in animals treated with cyclosporine compared to saline-treated controls. Conclusions. Topical cyclosporine A was effective in inhibiting the development of mast cell-mediated allergic conjunctivitis in mice. This study suggests that topical cyclosporine A may be effective in treating allergic conjunctivitis in humans. RP Whitcup, SM (reprint author), NEI, NIH, 10 CTR DR, BLDG 10, ROOM 10N 202, BETHESDA, MD 20892 USA. NR 28 TC 28 Z9 28 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1996 VL 37 IS 13 BP 2686 EP 2693 PG 8 WC Ophthalmology SC Ophthalmology GA VZ427 UT WOS:A1996VZ42700020 PM 8977483 ER PT J AU Ortego, J Escribano, J Becerra, SP CocaPrados, M AF Ortego, J Escribano, J Becerra, SP CocaPrados, M TI Gene expression of the neurotrophic pigment epithelium-derived factor in the human ciliary epithelium - Synthesis and secretion into the aqueous humor SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE aqueous humor fluid; ciliary epithelium; gene expression; neurotrophic factor; pigment epithelium-derived factor (PEDF) ID CELLULAR-DISTRIBUTION; CDNA; CELLS; IDENTIFICATION; ISOFORMS; PROTEIN; PLASMA; SERPIN; PEDF AB Purpose. To study the expression of the neurotrophic pigment epithelium-derived factor (PEDF), a protein with neurotrophic and neuronal-survival activities, by the human ocular ciliary epithelium. Methods. Total RNA extracted from human and bovine ocular tissues were screened by Northern blot analysis with cDNA probes for PEDF. Antibodies to PEDF were used to monitor its synthesis and secretion by metabolically labeling ciliary processes in vitro with S-35-methionine, followed by immunoprecipitation. Pigment epithelium-derived factor antibodies also were used to visualize the cellular distribution of PEDF along the human and bovine ciliary epithelium. Polymerase chain reaction (PCR) and reverse transcription (RT)-PCR was used to screen cDNA libraries of tissue and cell lines derived from the ciliary epithelium to demonstrate PEDF expression. Results. From a subtractive library of the human ocular ciliary body, the authors identified a cDNA clone exhibiting nucleotide homology with the PEDF. Northern blot analysis indicated that PEDF transcripts are present in all the ocular tissues in the human eye; in the bovine eye, it is expressed preferentially in the retinal pigment epithelium. RT-PCR and PCR demonstrated that the PEDF gene is still transcriptionally active in cultured cell lines derived from the bilayer of the ciliary epithelium. Immunoprecipitation and Western blot (immunoblot) analyses with antisera to the PEDF protein demonstrated that a predominant PEDF form of 46 kDa is synthesized in the ciliary body and is secreted as a glycoprotein of 50 kDa. By indirect immunofluorescence and immunocytochemistry, PEDF antibodies decorated both cell types that comprise the ciliary epithelium (nonpigmented and pigmented) and, more distinctively, the plasma-membrane domain of nonpigmented cells in the pars plicata region. Conclusions. These results reveal a new site of synthesis (ciliary epithelium) and accumulation (aqueous humor) of PEDF, and they emphasize its potential importance as a trophic factor in the neuro-differentiated functions of the human ciliary epithelium. C1 YALE UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,NEW HAVEN,CT 06510. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD. RI ortego, javier/K-6020-2014; OI ortego, javier/0000-0002-4275-7277; Escribano, Julio/0000-0002-8919-8134 FU NEI NIH HHS [EY00785, EY04873] NR 25 TC 71 Z9 77 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1996 VL 37 IS 13 BP 2759 EP 2767 PG 9 WC Ophthalmology SC Ophthalmology GA VZ427 UT WOS:A1996VZ42700029 PM 8977492 ER PT J AU Tomonaga, M Oka, M Narasaki, F Fukuda, M Nakano, R Takatani, H Ikeda, K Terashi, K Matsuo, I Soda, H Cowan, KH Kohno, S AF Tomonaga, M Oka, M Narasaki, F Fukuda, M Nakano, R Takatani, H Ikeda, K Terashi, K Matsuo, I Soda, H Cowan, KH Kohno, S TI The multidrug resistance-associated protein gene confers drug resistance in human gastric and colon cancers SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE multidrug resistance; MRP; gastric cancer; colon cancer; modulating agent ID PRODUCT P-GLYCOPROTEIN; CELL-LINE; HUMAN-TISSUES; MYELOID-LEUKEMIA; TUMOR-CELLS; MRP; EXPRESSION; OVEREXPRESSION; GLUTATHIONE; ACCUMULATION AB To determine the expression of multidrug resistance-associated protein (MRP) gene and its role in gastric and colon cancers, we analyzed 10 gastric and 10 colon non-drug-selected cell lines and a similar number of tissue samples of these cancers. We compared the expression of MRP and mdr1 mRNA in cell lines and tissues using reverse-transcriptase polymerase chain reaction. In mdr1-negative cells, the relationship between the level of MRP gene expression and sensitivity to anticancer drugs was examined. The effect of verapamil, an MRP-modulating agent, was also examined in these cells. The expression of MRP gene in gastric cancer cell lines varied from a low to a high level, but mdr1 was not detected in any of these cell lines. Colon cancer cell lines expressed low to intermediate levels of MRP gene, and half of the cells co-expressed low to high levels of mdr1. In tissue samples, the expression pattern of the two multidrug resistance (MDR) genes was broadly similar to that described for the cell lines, except that most of the gastric cancer tissue samples did express low levels of mdr1. No significant correlation was observed between the level of MRP gene expression and sensitivity to anticancer drugs in gastric and colon cell lines. However, verapamil significantly increased the sensitivity to etoposide, doxorubicin and vincristine in cells highly expressing MRP gene. Our results indicate that MRP gene may be important in conferring MDR in gastric and colon cancer cells. C1 NAGASAKI UNIV,SCH MED,DEPT INTERNAL MED 2,NAGASAKI 852,JAPAN. NATL CANC INST,MED BRANCH,BETHESDA,MD. NR 46 TC 41 Z9 43 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1996 VL 87 IS 12 BP 1263 EP 1270 PG 8 WC Oncology SC Oncology GA WC099 UT WOS:A1996WC09900012 PM 9045962 ER PT J AU Rogers, AS Futterman, D Levin, L DAngelo, L AF Rogers, AS Futterman, D Levin, L DAngelo, L TI A profile of human immunodeficiency virus-infected adolescents receiving health care services at selected sites in the United States SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; HIV infection; AIDS ID NEW-YORK-CITY; HIV-INFECTION; HEMOPHILIC SUBJECTS; CHILDREN; AGE; SEROPREVALENCE; GROWTH; AIDS; RISK; PREVALENCE AB Objective: To determine the demographic/clinical profile of human immunodeficiency virus (HIV)-infected adolescents in care at selected sites. Methods: We mailed surveys requesting prevalence data from physicians in government-funded HIV research and care programs on HIV-infected youth (10-21 years) receiving care. Results: A total of 49% responses yielded information on 978 subjects. Vertical, blood, and sexual were predominant transmission modes. Three-quarters were of an ethnic/racial minority; 50% were female. The earliest median CD, count was 0.467 x 10(9)/liter (467/mu l). Percent asymptomatic varied by transmission: vertical (16%), blood products (40%), male-male sexual (67%) and female-male sexual (M: 73%) (F: 74%). Clinically indicated Pneumocystis carinii pneumonia prophylaxis was differentially prescribed: vertical (96%), blood (89%), and sexual (male-male-47%) (female-male: M: 36% and F: 56%). Of these youth 78% are not represented in national AIDS case data. Conclusions: Examination of numerator data from selected sites indicates three transmission-driven adolescent HIV epidemics with different characteristics. Minority youth are disproportionately represented; many vertically infected infants are surviving to adolescence; sexual activity is a significant transmission avenue. HIV-infected youth appear to enter care with considerable immunosuppression. Clinical profiles and treatment patterns appear to differ by transmission mode. Further study is needed on adolescent HIV disease progression and determinants of access to care and treatment. C1 ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,ADOLESCENT AIDS PROGRAM,NEW YORK,NY. MT SINAI MED CTR,MT SINAI SCH MED,ADOLESCENT AIDS PROGRAM,NEW YORK,NY 10029. GEORGE WASHINGTON UNIV,DEPT ADOLESCENT & YOUNG ADULT MED,CHILDRENS NATL MED CTR,WASHINGTON,DC. RP Rogers, AS (reprint author), NICHHD,PAMAB,CRMC,NIH,6100 BLDG ROOM 4B11,6100 EXECUT BLVD MSC 7510,BETHESDA,MD 20892, USA. NR 40 TC 25 Z9 25 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 1996 VL 19 IS 6 BP 401 EP 408 DI 10.1016/S1054-139X(96)00051-1 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA VY334 UT WOS:A1996VY33400007 PM 8969371 ER PT J AU Webb, TE Boluyt, MO Barnard, EA AF Webb, TE Boluyt, MO Barnard, EA TI Molecular biology of P-2Y purinoceptors: Expression in rat heart SO JOURNAL OF AUTONOMIC PHARMACOLOGY LA English DT Article; Proceedings Paper CT Meeting on the Role of Adenosine and ATP in the Cardiovascular System CY JUN 28-29, 1996 CL FREIBURG, GERMANY ID EXTRACELLULAR ATP; RECEPTOR; CLONING; NUCLEOTIDES; MYOCYTES; CELLS AB 1 Application of molecular biology to the study of P-2Y purinoceptors has led to the identification of seven such receptors. Here we briefly review their properties and investigate qualitatively the expression of four rat receptor transcripts in heart. 2 The reverse transcriptase-polymerase chain reaction was used to ascertain whether the rat P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptor transcripts were expressed in whole heart, neonatal cardiac fibroblasts, neonatal cardiac myocytes and adult cardiac myocytes. 3 All receptor sequences could be amplified from neonatal rat whole heart, with P2Y(6) appearing the most abundant transcript of the four. P2Y(1) is expressed at higher levels in comparison to P2Y(2), P2Y(4) and P2Y(6) in the neonatal myocyte. In the adult myocyte P2Y(1), P2Y(2) and P2Y(6) could be amplified but P2Y(4) could not be detected. In the neonatal fibroblast, P2Y(1) and P2Y(6) appear to be expressed at higher levels than P2Y(2) and P2Y(4). 4 In summary, it is concluded that multiple P2Y receptor subtypes are expressed in heart and that the expression in myocytes changes from the neonate to the adult. C1 NIA, CARDIOVASC SCI LAB, CTR GERONTOL RES, NIH, BALTIMORE, MD 21224 USA. RP Webb, TE (reprint author), ROYAL FREE HOSP, SCH MED, MOL NEUROBIOL UNIT, ROWLAND HILL ST, LONDON NW3 2PF, ENGLAND. FU Wellcome Trust NR 28 TC 49 Z9 53 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0144-1795 J9 J AUTON PHARMACOL JI J. Auton. Pharmacol. PD DEC PY 1996 VL 16 IS 6 BP 303 EP 307 DI 10.1111/j.1474-8673.1996.tb00040.x PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA WU202 UT WOS:A1996WU20200003 PM 9131403 ER PT J AU Hobbs, LJ Nossal, NG AF Hobbs, LJ Nossal, NG TI Either bacteriophage T4 RNase H or Escherichia coli DNA polymerase I is essential for phage replication SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEIN; ORIGIN; GENES; ORGANIZATION; EXPRESSION; MUTATIONS; INVITRO; PRIMERS; REGION; GENOME AB Bacteriophage T4 rnh encodes an RNase H that removes ribopentamer primers from nascent DNA chains during synthesis by the T4 multienzyme replication system in vitro (H. C. Hollingsworth and N. G. Nossal, J. Biol. Chem. 266:1888-1897, 1991), This paper demonstrates that either T4 RNase HI or Escherichia coli DNA polymerase I (Pol I) is essential for phage replication. Wild-type T4 phage production was not diminished by the pol-Al2 mutation, which disrupts coordination between the polymerase and the 5'-to-3' nuclease activities of E. coli DNA Pol I, or by an interruption in the gene for E. coli RNase HI. Deleting the C-terminal amino acids 118 to 305 from T4 RNase H reduced phage production to 47% of that of wild-type T4 on a wild-type E. coli host, 10% on an isogenic host defective in RNase H, and less than 0.1% on a polA12 host, The T4 rnh(Delta 118-305) mutant synthesized DNA at about half the rate of wild-type T4 in the polA12 host. More than 50% of pulse-labelled mutant DNA was in short chains characteristic of Okazaki fragments, Phage production was restored in the nonpermissive host by providing the T4 rnh gene on a plasmid. Thus, T4 RNase H was sufficient to sustain the high rate of T4 DNA synthesis, but E. coli RNase HI and the 5'-to-3' exonuclease of Pol I could substitute to some extent for the T4 enzyme, However, replication was less accurate in the absence of the T4 RNase Ht as judged by the increased frequency of acriflavine-resistant mutations after infection of a wild-type host with the T4 rnh(Delta 118-305) mutant. C1 NIDDKD,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. NR 34 TC 21 Z9 21 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 DEC PY 1996 VL 178 IS 23 BP 6772 EP 6777 PG 6 WC Microbiology SC Microbiology GA VW223 UT WOS:A1996VW22300018 PM 8955295 ER PT J AU Wang, P Denoya, CD Morgenstern, MR Skinner, DD Wallace, KK Digate, R Patton, S Banavali, N Schuler, G Speedie, MK Reynolds, KA AF Wang, P Denoya, CD Morgenstern, MR Skinner, DD Wallace, KK Digate, R Patton, S Banavali, N Schuler, G Speedie, MK Reynolds, KA TI Cloning and characterization of the gene encoding 1-cyclohexenylcarbonyl coenzyme A reductase from Streptomyces collinus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CYCLOHEXANECARBOXYLIC ACID MOIETY; ANTIFUNGAL ANTIBIOTICS PHOSLACTOMYCINS; DROSOPHILA ALCOHOL-DEHYDROGENASE; ESCHERICHIA-COLI; ANSATRIENIN-A; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; RNA-POLYMERASE; CHICKEN LIVER; TRIENOMYCIN-A AB We report the cloning of the gene encoding the 1-cyclohexenylcarbonyl coenzyme A reductase (ChcA) of Streptomyces collinus, an enzyme putatively involved in the final reduction step in the formation of the cyclohexyl moiety of ansatrienin from shikimic acid. The cloned gene, with a proposed designation of chcA, encodes an 843-bp open reading frame which predicts a primary translation product of 280 amino acids and a calculated molecular mass of 29.7 kDa, Highly significant sequence similiarity extending along almost the entire length of the protein was observed with members of the short-chain alcohol dehydrogenase superfamily. The S. collinus chcA gene was overexpressed in Escherichia coli by using a bacteriophage T7 transient expression system, and a protein with a specific ChcA activity was detected, The E. coli-produced ChcA protein was purified and shown to have similar steady-state kinetics and electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels as the enoyl-coenzyme A reductase protein prepared from S. collinus. The enzyme demonstrated the ability to catalyze, in vitro, three of the reductive steps involved in the formation of cyclohexanecarboxylic acid. An S. collinus chcA mutant, constructed by deletion of a genomic region comprising the 5' end of chcA, lost the ChcA activity and the ability to synthesize either cyclohexanecarboxylic acid or ansatrienin. These results suggest that chc4 encodes the ChcA that is involved in catalyzing multiple reductive steps in the pathway that provides the cyclohexanecarboxylic acid from shikimic acid. C1 UNIV MARYLAND, SCH PHARM, DEPT PHARMACEUT SCI, BALTIMORE, MD 21201 USA. UNIV MARYLAND, CTR MED BIOTECHNOL, MED BIOTECHNOL INST, BALTIMORE, MD 21201 USA. NIH, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. PFIZER INC, DIV CENT RES, GROTON, CT 06340 USA. OI Banavali, Nilesh/0000-0003-2206-7049 NR 68 TC 24 Z9 24 U1 1 U2 2 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 DEC PY 1996 VL 178 IS 23 BP 6873 EP 6881 PG 9 WC Microbiology SC Microbiology GA VW223 UT WOS:A1996VW22300032 PM 8955309 ER PT J AU Christie, GE Cale, SB Isaksson, LA Jin, DJ Xu, M Sauer, B Calendar, R AF Christie, GE Cale, SB Isaksson, LA Jin, DJ Xu, M Sauer, B Calendar, R TI Escherichia coli rpoC397 encodes a temperature-sensitive C-terminal frameshift in the beta' subunit of RNA polymerase that blocks growth of bacteriophage P2 SO JOURNAL OF BACTERIOLOGY LA English DT Article AB Escherichia coli 397c is temperature sensitive for growth at 43.5 degrees C and unable to plate bacteriophage P2 at 33 degrees C. The mutation conferring these phenotypes was mapped to the rpoC gene. RNA synthesis is temperature sensitive in the mutant strain, and the beta' subunit of RNA polymerase isolated from this strain exhibits increased electrophoretic mobility. DNA sequence analysis revealed that the mutation is a deletion of 16 bp, resulting in a frameshift that leads to truncation of the beta' subunit at the carboxy terminus. C1 UNIV STOCKHOLM,DEPT MICROBIOL,S-10691 STOCKHOLM,SWEDEN. NCI,MOL BIOL LAB,BETHESDA,MD 20892. UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,BERKELEY,CA 94720. RP Christie, GE (reprint author), VIRGINIA COMMONWEALTH UNIV,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298, USA. FU NIAID NIH HHS [AI08722] NR 13 TC 17 Z9 17 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 DEC PY 1996 VL 178 IS 23 BP 6991 EP 6993 PG 3 WC Microbiology SC Microbiology GA VW223 UT WOS:A1996VW22300047 PM 8955324 ER PT J AU Rouault, TA Klausner, RD AF Rouault, TA Klausner, RD TI Post-transcriptional regulation of genes of iron metabolism in mammalian cells SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE iron; iron-sulfur proteins; aconitase; IRE; IRP1 and IRP2 ID IRON-RESPONSIVE-ELEMENT; RNA-BINDING PROTEIN; SYNTHASE MESSENGER-RNA; 3' UNTRANSLATED REGION; TRANSFERRIN RECEPTOR; SULFUR CLUSTER; TRANSLATIONAL REPRESSOR; CYTOSOLIC ACONITASE; HIGH-AFFINITY; FERRITIN AB Iron metabolism is tightly regulated in mammalian cells. Here we describe several types of post-transcriptional mechanisms that have been identified in regulation of genes of iron metabolism. Iron-dependent regulation of stability of the transcript is the key to regulation of the expression of the transferrin receptor, Selective repression of translation in iron-depleted cells is the key to regulation of the expression of ferritin and several other genes that require iron for function. Specific regulatory proteins that directly sense iron levels in cells are needed to coordinate iron metabolism. These proteins, known as iron regulatory proteins (IRPs), bind to specific RNA stem-loops in transcripts with high affinity when cells are depleted of iron. The two IRPS, IRP1 and IRP2, are post-translationally modified by iron, but the nature of the post-translational regulatory process differs. IRP1 assembles an iron-sulfur cluster which determines its function, whereas IRP1 is rapidly degraded in the presence of iron. Direst binding of iron is likely to be involved in sensing of iron levels by IRP1 and IRP2. Although each IRP binds to the RNA stem-loop motifs known as iron-responsive elements (IREs) with high affinity, it is possible that each protein binds an additional, unique set of target-binding motifs. The list of potential genes that are regulated by IRPs continues to grow, and much remains to be learned about the regulation of mammalian iron metabolism. RP Rouault, TA (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 64 TC 38 Z9 39 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD DEC PY 1996 VL 1 IS 6 BP 494 EP 499 DI 10.1007/s007750050083 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA WA565 UT WOS:A1996WA56500002 ER PT J AU Cooper, GS Umbach, DM AF Cooper, GS Umbach, DM TI Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GENE POLYMORPHISM; OSTEOPOROTIC WOMEN; ALLELES; GENOTYPES; LOCUS; BSMI; MASS; VIEW AB Vitamin D receptor (VDR) polymorphisms have been strongly associated with bone mineral density (BMD) in some studies but not in others. We used a meta-analytic approach to assess quantitatively the association between VDR and BMD and to examine the influence of specific study characteristics (e.g., skeletal site, mean age of subjects, menopausal status) on the reported results. Sixteen papers published in peer-reviewed journals through July 1996 were included. We calculated the mean difference, percent difference, and effect size (mean difference divided by standard deviation), comparing BMD between homozygous genotypes. At the hip, BMD in the BE genotype was lower than in the bb genotype (mean difference, -0.02 g/cm(2); percent difference, -2.4%; and effect size -0.18; p = 0.032). At the spine, the mean difference was -0.03 g/cm(2); percent difference, -2.5%; and effect size, -0.19; p = 0.062. At the distal radius, the VDR effect was estimated as the mean difference, -0.01 g/cm(2); percent difference, -1.7%; and effect size, -0.16; p = 0.078. The spine measurements exhibited the greatest between- and within-study variability. The difference in hip BMD between genotypes was larger (i.e., a more negative number) among the younger women and seemed to decrease with increasing age. However, statistical evidence for this trend was weak (p = 0.06). Data from the spine and the radius showed no evidence of a comparable interaction of the VDR effect with age. When we omitted data from the first report of an association between VDR polymorphisms and BMD, our analyses gave similar results, although the overall effect estimates were smaller. In the combined data from 29 study groups, the BE genotype frequency was 17.2, 4.9, and 2.3% in studies of whites, blacks, and Asians, respectively. VDR polymorphisms represent one genetic factor affecting BMD, but further research into the mechanisms, clinical significance, and its relation between other genetic and environmental factors is needed. C1 NIEHS, STAT & BIOMATH BRANCH, RES TRIANGLE PK, NC 27709 USA. RP Cooper, GS (reprint author), NIEHS, EPIDEMIOL BRANCH A305, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 33 TC 333 Z9 346 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1996 VL 11 IS 12 BP 1841 EP 1849 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY562 UT WOS:A1996VY56200002 PM 8970884 ER PT J AU Remmers, EF Du, Y Ding, YP Kotake, S Ge, L Zha, HB Goldmuntz, EA Hansen, C Wilder, RL AF Remmers, EF Du, Y Ding, YP Kotake, S Ge, L Zha, HB Goldmuntz, EA Hansen, C Wilder, RL TI Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID SINGLE LINKAGE GROUP; POLYMORPHIC LOCI; MAP; MOUSE; MUTATION; BONE; MICE; MARKERS AB Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN.+/op) F1 carriers, we mapped this locus by linkage analysis with microsatellite markers to rat chromosome 10, The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]-1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog-2, and proline-rich protein). The markers for these loci include nine not previously reported. The op Locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its location, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect. C1 NIH,NATL CTR RES RESOURCES,GENET RESOURCES SECT,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP Remmers, EF (reprint author), NIH,NIAMSD,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA. NR 32 TC 8 Z9 8 U1 0 U2 0 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 DEC PY 1996 VL 11 IS 12 BP 1856 EP 1861 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY562 UT WOS:A1996VY56200004 PM 8970886 ER PT J AU Miyamoto, S Teramoto, H Gutkind, JS Yamada, KM AF Miyamoto, S Teramoto, H Gutkind, JS Yamada, KM TI Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: Roles of integrin aggregation and occupancy of receptors SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MEDIATED CELL-ADHESION; SIGNAL-TRANSDUCTION; EXTRACELLULAR-MATRIX; PROTEIN-KINASE; ENDOTHELIAL-CELLS; GENE-EXPRESSION; FIBRONECTIN; CYTOSKELETAL; PATHWAYS; CALCIUM AB Integrins mediate cell adhesion, migration, and a variety of signal transduction events. These integrin actions can overlap or even synergize with those of growth factors. We examined for mechanisms of collaboration or synergy between integrins and growth factors involving MAP kinases, which regulate many cellular functions. In cooperation with integrins, the growth factors EGF, PDGF-BB, and basic FGF each produced a marked, transient activation of the ERK (extracellular signal-regulated kinase) class of MAP kinase, but only if the integrins were both aggregated and occupied by ligand. Transmembrane accumulation of total tyrosine-phosphorylated proteins, as well as nonsynergistic MAP kinase activation, could be induced by simple integrin aggregation, whereas enhanced transient accumulation of the EGF-receptor substrate eps8 required integrin aggregation and occupancy, as well as EGF treatment. Each type of growth factor receptor was itself induced to aggregate transiently by integrin ligand-coated beads in a process requiring both aggregation and occupancy of integrin receptors, but not the presence of growth factor ligand. Synergism was also observed between integrins and growth factors for triggering tyrosine phosphorylation of EGF, PDGF, and FGF receptors. This collaborative response also required both integrin aggregation and occupancy. These studies identify mechanisms in the signal transduction response to integrins and growth factors that require various combinations of integrin aggregation and ligands for integrin or growth factor receptors, providing opportunities for collaboration between these major regulatory systems. C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009; OI Yamada, Kenneth/0000-0003-1512-6805 NR 59 TC 597 Z9 606 U1 1 U2 10 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 DEC PY 1996 VL 135 IS 6 BP 1633 EP 1642 DI 10.1083/jcb.135.6.1633 PN 1 PG 10 WC Cell Biology SC Cell Biology GA VZ316 UT WOS:A1996VZ31600016 PM 8978828 ER PT J AU Plonsky, I Zimmerberg, J AF Plonsky, I Zimmerberg, J TI The initial fusion pore induced by baculovirus GP64 is large and forms quickly SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEMAGGLUTININ EXPRESSING CELLS; PLANAR BILAYER-MEMBRANES; VIRAL ENVELOPE PROTEIN; INFLUENZA HEMAGGLUTININ; CAPACITANCE MEASUREMENTS; SECRETORY VESICLE; PATCH-CLAMP; MAST-CELLS; EXOCYTOSIS; EVENTS AB The formation of the fusion pore is the first detectable event in membrane fusion (Zimmerberg, J., R. Blumenthal, D.P. Sarkar, M. Curran, and S.J. Morris. 1994, J. Cell Biol. 127:1885-1894). To date, fusion pores measured in exocytosis and viral fusion have shared features that include reversible closure (flickering), highly fluctuating semistable stages, and a lag time of at least several seconds between the triggering and the pore opening. We investigated baculovirus GP64-induced Sf9 cell-cell fusion, triggered by external acid solution, using two different electrophysiological techniques: double whole-cell recording (for high time resolution, model-independent measurements), and the more conventional time-resolved admittance recordings. Both methods gave essentially the same results, thus validating the use of the admittance measurements for fusion pore conductance calculations. Fusion was first detected by abrupt pore formation with a wide distribution of initial conductance, centered around 1 nS. Often the initial fusion pore conductance was stable for many seconds. Fluctuations in semistable conductances were much less than those of other fusion pores, The waiting rime distribution, measured between pH onset and initial pore appearance, fits best to a model with many (similar to 19) independent elements. Thus, unlike previously measured fusion pores, GP64-mediated pores do not flicker, can have large, stable initial pore conductances lasting up to a minute, and have typical lag times of < 1 s, These findings are consistent with a barrel-shaped model of an initial fusion pore consisting of five to eight GP64 trimers that is lined with lipid. C1 NICHHD,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. NR 48 TC 68 Z9 70 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1996 VL 135 IS 6 BP 1831 EP 1839 DI 10.1083/jcb.135.6.1831 PN 2 PG 9 WC Cell Biology SC Cell Biology GA WA879 UT WOS:A1996WA87900013 PM 8991094 ER PT J AU Morasso, MI Markova, NG Sargent, TD AF Morasso, MI Markova, NG Sargent, TD TI Regulation of epidermal differentiation by a Distal-less homeodomain gene SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSGENIC MICE; HOMEOBOX GENES; ACID RECEPTOR; EXPRESSION; PROTEIN; KERATINOCYTE; ENVELOPE; CELLS; FOREBRAIN; LORICRIN AB The Distal-less-related homeodomain gene Dlx3 is expressed in terminally differentiated murine epidermal cells. Ectopic expression of this gene in the basal cell layer of transgenic skin results in a severely abnormal epidermal phenotype and leads to perinatal lethality. The basal cells of affected mice ceased to proliferate, and expressed the profilaggrin and loricrin genes which are normally transcribed only in the latest stages of epidermal differentiation. All suprabasal cell types were diminished and the stratum corneum was reduced to a single layer. These data indicate that Dlx3 misexpression results in transformation of basal cells into more differentiated keratinocytes, suggesting that this homeoprotein is an important regulator of epidermal differentiation. C1 NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. RP Morasso, MI (reprint author), NICHHD,GENET MOL LAB,NIH,BLDG 6B,ROOM 412,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [Z01 AR041124-06] NR 43 TC 90 Z9 93 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1996 VL 135 IS 6 BP 1879 EP 1887 DI 10.1083/jcb.135.6.1879 PN 2 PG 9 WC Cell Biology SC Cell Biology GA WA879 UT WOS:A1996WA87900017 PM 8991098 ER PT J AU Ralston, E Ploug, T AF Ralston, E Ploug, T TI GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor and stored in vesicles associated with the TGN SO JOURNAL OF CELL SCIENCE LA English DT Article DE muscle; GLUT4; Golgi complex ID TRANS-GOLGI NETWORK; GLUCOSE-TRANSPORTER GLUT4; MICROTUBULE-ORGANIZING CENTERS; L6 MUSCLE-CELLS; BREFELDIN-A; 3T3-L1 ADIPOCYTES; RAT ADIPOCYTES; INSULIN STIMULATION; ORGANELLE STRUCTURE; CYTOPLASMIC DOMAIN AB There is little consensus on the nature of the storage compartment of the glucose transporter GLUT4, in non-stimulated cells of muscle and fat, More specifically, it is not known whether GLUT4 is localized to unique, specialized intracellular storage vesicles, or to vesicles that are part of the constitutive endosomal-lysosomal pathway, To address this question, we have investigated the localization of the endogenous GLUT4 in non-stimulated skeletal myotubes from the cell line C2, by immunofluorescence and immunoelectron microscopy, We have used a panel of antibodies to markers of the Golgi complex (alpha mannosidase II and giantin), of the trans-Golgi network (TGN38), of lysosomes (Igp110), and of early and late endosomes (transferrin receptor and mannose-6-phosphate receptor, respectively), to define the position of their subcellular compartments, By immunofluorescence, GLUT4 appears concentrated in the core of the myotubes, It is primarily found around the nuclei, in a pattern suggesting an association with the Golgi complex, which is further supported by colocalization with giantin and by immunogold electron microscopy, GLUT4 appears to be in the trans-most cisternae of the Golgi complex and in vesicles just beyond, i.e. in the structures that constitute the trans-Golgi network (TGN), In myotubes treated with brefeldin A, the immunofluorescence pattern of GLUT4 is modified, but it differs from both Golgi complex markers and TGN38, Instead, it resembles the pattern of the transferrin receptor, which forms long tubules, In untreated cells, double staining for GLUT4 and transferrin receptor by immunofluorescence shows similar but distinct patterns, Immunoelectron microscopy localizes transferrin receptor, detected by immunoperoxidase, to large vesicles, presumably endosomes, very close to the GLUT4-containing tubulovesicular elements, In brefeldin A-treated cells, a network of tubules of similar to 70 nm diameter, studded with varicosities, stains for both GLUT4 and transferrin receptor, suggesting that brefeldin A has caused fusion of the transferrin receptor and GLUT4-containing compartments, The results suggest that GLUT4 storage vesicles constitute a specialized compartment that is either a subset of the TGN, or is very closely linked to it, The link between GLUT4 vesicles and transferrin receptor containing endosomes, as revealed by brefeldin A, may be important for GLUT4 translocation in response to muscle stimulation. C1 NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. RIGSHOSP,COPENHAGEN MUSCLE RES CTR,COPENHAGEN,DENMARK. RP Ralston, E (reprint author), NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 63 TC 50 Z9 50 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC PY 1996 VL 109 BP 2967 EP 2978 PN 13 PG 12 WC Cell Biology SC Cell Biology GA WB438 UT WOS:A1996WB43800002 PM 9004032 ER PT J AU MartinezLacaci, I Johnson, GR Salomon, DS Dickson, RB AF MartinezLacaci, I Johnson, GR Salomon, DS Dickson, RB TI Characterization of a novel amphiregulin-related molecule in 12-O-tetradecanoylphorbol-13-acetate-treated breast cancer cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; MAMMARY EPITHELIAL-CELLS; HEPARIN-BINDING DOMAIN; PROTEIN-KINASE-C; FACTOR-ALPHA; PHORBOL ESTER; HUMAN COLON; SURFACE; EXPRESSION; PRECURSOR AB Amphiregulin (AR) can be induced at the mRNA level by 17-beta-estradiol (E(2)) or the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study compares the effects of TPA and E(2) on the regulation of processing of AR isoforms and on subcellular localization in human MCF-7 breast cancer cells. AR was localized in the nucleus of MCF-7 cells after E(2) treatment, whereas it was predominantly secreted after TPA treatment. AR isoforms of 28, 18, and 10 kDa and an additional species of approximately 55-60 kDa were detected in the cellular conditioned media after TPA stimulation. Expression of this unusual AR isoform was inhibited by protein kinase C (PKC) inhibitors such as bryostatin or H-7. The biochemical properties of this isoform are consistent with it being an N-linked glycosylated form of the AR precursor that contains unprocessed mannose residues. The size of this large isoform is reduced to approximately 40 kDa after treating the TPA-induced MCF-7 cells with tunicamycin or treating the conditioned media of such cells with N-glycosidase F or with endoglycosidase H. Moreover, this isoform is able to bind several lectins with specificity for mannose residues. The 55-60 kDa glycosylated AR isoform, like lower Mr AR isoforms, is able to bind to heparin and to stimulate the growth of MCF-10A cells by interacting with the EGF receptor. These data suggest that TPA activation of PKC may be involved in post-translational modifications of AR, such as glycosylation, and in alteration of its subcellular routing to predominantly a secretory pathway. (C) 1996 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC 20007. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 47 TC 11 Z9 11 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1996 VL 169 IS 3 BP 497 EP 508 DI 10.1002/(SICI)1097-4652(199612)169:3<497::AID-JCP10>3.0.CO;2-3 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VW030 UT WOS:A1996VW03000010 PM 8952699 ER PT J AU Pratley, RE Nicolson, M Bogardus, C Ravussin, E AF Pratley, RE Nicolson, M Bogardus, C Ravussin, E TI Effects of acute hyperinsulinemia on plasma leptin concentrations in insulin-sensitive and insulin-resistant Pima Indians SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID WHITE ADIPOSE-TISSUE; OB GENE-EXPRESSION; OBESE AB Leptin, a recently discovered protein produced in adipocytes, may be important in the regulation of body energy stores. In humans, leptin is present in the circulation in direct proportion to the amount of body fat. In rodents, insulin seems to regulate the production of leptin, but there is only limited evidence that this occurs in humans. We, therefore, measured plasma leptin concentrations in 13 insulin-sensitive and 13 insulin-resistant Pima Indians at baseline, at the end of 100 min of physiologic hyperinsulinemia (mean plasma insulin = 563 pmol/L) and after a further 100 min of supraphysiologic hyperinsulinemia (mean plasma insulin = 11,910 pmol/L), during a 2-step hyperinsulinemic-euglycemic glucose clamp. At baseline, plasma leptin concentrations were directly related to percent body fat, determined by hydrodensitometry (r = 0.85, P < 0.0001). After adjusting for percent body fat, there were no differences in fasting plasma leptin concentrations between insulin-sensitive and insulin-resistant subjects. Plasma leptin concentrations did not change in response to insulin in either the insulin-sensitive or insulin-resistant subjects. These results suggest that insulin does not acutely regulate plasma leptin concentrations in humans. C1 NIDDKD, PHOENIX EPIDEMIOL & CLIN RES BRANCH, NIH, PHOENIX, AZ 85016 USA. AMGEN INC, THOUSAND OAKS, CA 91320 USA. RP Pratley, RE (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, PHOENIX, AZ 85016 USA. NR 19 TC 71 Z9 72 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 DEC PY 1996 VL 81 IS 12 BP 4418 EP 4421 DI 10.1210/jc.81.12.4418 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW462 UT WOS:A1996VW46200040 PM 8954052 ER PT J AU Gordon, VM Bonkovsky, FO AF Gordon, VM Bonkovsky, FO TI Family dynamics and children in medical research SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 FAC UNIV VIENNA,VIENNA,AUSTRIA. RP Gordon, VM (reprint author), NIDR,NIH,BETHESDA,MD 20892, USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 1996 VL 7 IS 4 BP 349 EP 354 PG 6 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA WE870 UT WOS:A1996WE87000011 PM 9029336 ER PT J AU Tseng, CC Kieffer, TJ Jarboe, LA Usdin, TB Wolfe, MM AF Tseng, CC Kieffer, TJ Jarboe, LA Usdin, TB Wolfe, MM TI Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP) - Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE glucagonlike peptide-1 (7-36) (GLP-1); incretin; insulin; GIP receptor ID GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; PHYSIOLOGICAL INCRETIN; FUNCTIONAL EXPRESSION; GLP-1 7-36AMIDE; PANCREAS; SECRETION; BLOOD; AMIDE; GENE AB Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide produced by K cells of the mammalian proximal small intestine and is a potent stimulant of insulin release in the presence of hyperglycemia, However, its relative physiological importance as a postprandial insulinotropic agent is unknown. Using LGIPR2 cells stably transfected with rat GIP receptor cDNA, GIP (1-42) stimulation of cyclic adenosine monophosphate (cAMP) production was inhibited in a concentration-dependent manner by GIP (7-30)-NH2. Competition binding assays using stably transfected L293 cells demonstrated an IC50 for GIP receptor binding of 7 nmol/liter for GIP (1-42) and 200 nmol/liter for GIP (7-30)-NH2, whereas glucagonlike peptide-1 (GLP-1) binding to its receptor on beta TC3 cells was minimally displaced by GIP (7-30)-NH2. In fasted anesthetized rats, GTP (1-42) stimulated insulin release in a concentration-dependent manner, an effect abolished by the concomitant intraperitoneal administration of GIP (7-30)-NH2 (100 nmol/ kg). In contrast, glucose-, GLP-1-, and arginine-stimulated insulin release were not affected by GIP (7-30)-NH2. In separate experiments, GIP (7-30)-NH2 (100 nmol/kg) reduced postprandial insulin release in conscious rats by 72%. It is concluded that GIP (7-30)-NH2 is a GIP-specific receptor antagonist and that GIP plays a dominant role in mediating postprandial insulin release. C1 BRIGHAM & WOMENS HOSP,DIV GASTROENTEROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MOL ENDOCRINOL LAB,BOSTON,MA 02114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [KO8DK-08753, R01DK-48042] NR 32 TC 105 Z9 110 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 1 PY 1996 VL 98 IS 11 BP 2440 EP 2445 DI 10.1172/JCI119060 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VX291 UT WOS:A1996VX29100004 PM 8958204 ER PT J AU Boirivant, M Pica, R DeMaria, R Testi, R Pallone, F Strober, W AF Boirivant, M Pica, R DeMaria, R Testi, R Pallone, F Strober, W TI Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE apoptosis; T lymphocytes; human intestinal lamina propria; regional immunity ID PERIPHERAL-BLOOD; DEATH APOPTOSIS; LYMPHOCYTES-T; CLONAL ANERGY; IN-VIVO; ACTIVATION; PROLIFERATION; EXPRESSION; RESPONSIVENESS; INTERLEUKIN-7 AB Lamina propria (LP)T cells respond poorly to a proliferative stimulus delivered via TCR/CD3 pathway, but retain considerable ability to respond to a stimulus delivered via CD2 costimulatory or accessory pathway. in the present study, we showed first that unstimulated LP T cells, as compared to unstimulated peripheral blood (PB)T cells, exhibit an increased level of apoptosis which is further increased following CD2 pathway stimulation, but not following via TCR/CD3 pathway stimulation. We next showed that IL-2 had a sparing effect on apoptosis of unstimulated LP T cells in that IL-2 decreased and anti-IL-2 increased apoptosis of these cells; in contrast, IL-2 had no effect on apoptosis of CD2-pathway stimulated eels. Finally, we showed that increased apoptosis of LP T cells induced by CD2-pathway stimulation is inhibited when Fas antigen is blocked by a nonstimulatory anti-Fas antibody. These studies suggest that LP T cells are characterized by increased susceptibility to Fas-mediated apoptosis most due to a downstream change in the Fas signaling pathway. Given that IFN-gamma secretion is significantly increased in LP T cells in which apoptosis is inhibited, this feature of LP T cells may represent a mechanism of regulating detrimental immune responses in the mucosal environment. C1 UNIV ROMA LA SAPIENZA,GI UNIV,ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,ROME,ITALY. UNIV REGGIO CALABRIA,DEPT EXPT MED,CATANZARO,ITALY. NIAID,NIH,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD. RP Boirivant, M (reprint author), IST SUPER SANITA,DEPT IMMUNOL,VIALE REGINA ELENA 299,I-00161 ROME,ITALY. RI BOIRIVANT, MONICA/B-9977-2016 NR 35 TC 103 Z9 105 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 1 PY 1996 VL 98 IS 11 BP 2616 EP 2622 DI 10.1172/JCI119082 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VX291 UT WOS:A1996VX29100026 PM 8958226 ER PT J AU Wang, ZH Hansson, BG Forslund, O Dillner, L Sapp, M Schiller, JT Bjerre, B Dillner, J AF Wang, ZH Hansson, BG Forslund, O Dillner, L Sapp, M Schiller, JT Bjerre, B Dillner, J TI Cervical mucus antibodies against human papillomavirus type 16, 18, and 33 capsids in relation to presence of viral DNA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; SERUM ANTIBODIES; INFECTION; IDENTIFICATION; SECRETIONS; NEOPLASIA AB To investigate whether cervical mucus antibodies against human papillomavirus (HPV) capsids are associated with the detection of HPV DNA or HPV-related cytological diagnoses, 611 samples of cervical secretions from 359 women referred to a colposcopy clinic were tested by an enzyme-linked immunosorbent assay for the presence of immunoglobulin A (IgA) antibodies against HPV capsids of HPV type 16, 18, or 33 and for the presence of cervical HPV DNA by PCR. Among subjects with at least one cervical sample positive for HPV type 16 (HPV-16) DNA, 28.1% also had at least one HPV-16 IgA-positive cervical sample (odds ratio [OR] = 2.9; P = 0.0003). IgA to HPV-18 was also more common among HPV-18 DNA-positive subjects (OR = 3.1; P = 0.0325) and IgA to HPV-33 was more common among HPV-33 DNA-positive subjects (OR = 4.2; P = 0.0023). Cervical IgA antibodies to HPV-16 were also more common among patients with cervical intraepithelial neoplasia, particularly among patients with cervical intraepithelial neoplasia grade I (P < 0.0005). The data indicate that an HPV type-restricted IgA antibody response against HPV capsids is detectable in cervical mucus and is associated with a concomitant cervical HPV infection. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. LUND UNIV,MALMO UNIV HOSP,DEPT MED MICROBIOL,MALMO,SWEDEN. LUND UNIV,MALMO UNIV HOSP,DEPT OBSTET & GYNECOL,MALMO,SWEDEN. UNIV MAINZ,DEPT MED MICROBIOL,MAINZ,GERMANY. NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 24 TC 34 Z9 36 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 DEC PY 1996 VL 34 IS 12 BP 3056 EP 3062 PG 7 WC Microbiology SC Microbiology GA VV005 UT WOS:A1996VV00500035 PM 8940448 ER PT J AU Tellier, R Bukh, J Emerson, SU Miller, RH Purcell, RH AF Tellier, R Bukh, J Emerson, SU Miller, RH Purcell, RH TI Long PCR and its application to hepatitis viruses: Amplification of hepatitis A, hepatitis B, and hepatitis C virus genomes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; COMPLETE NUCLEOTIDE-SEQUENCE; REACTION ASSAY; A VIRUS; DNA; RNA; CHIMPANZEES; STRAIN; SERUM AB In this study we amplified virtually the entire genomes of hepatitis A virus (a member of the Picornaviridae family), hepatitis B virus (a member of the Hepadnaviridae family), and hepatitis C virus (a member of the Flaviviridae family) by using the recently described technique of long PCR In order to do this, we first demonstrated, using the lambda phage, that long PCR can be made highly sensitive and that the sensitivity can de further enhanced by nested long PCR, We also showed, using tobacco mosaic virus as a model, that a reverse transcriptase reaction can be linked to a long PCR, enabling the dearly full-length amplification of the genomes of RNA viruses, We then applied these techniques to serial dilutions of titrated stocks of well-characterized strains of hepatitis A, B, and C viruses, We amplified the nearly full-length sequence of each of these viruses from a small number of viral genomes, demonstrating the sensitivity of the process. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NR 30 TC 41 Z9 44 U1 0 U2 2 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 DEC PY 1996 VL 34 IS 12 BP 3085 EP 3091 PG 7 WC Microbiology SC Microbiology GA VV005 UT WOS:A1996VV00500039 PM 8940452 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Hand preference for a bimanual task in tufted capuchins (Cebus apella) and rhesus macaques (Macaca mulatta) SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID CHIMPANZEES PAN-TROGLODYTES; MONKEYS; HANDEDNESS; INTELLIGENCE; LATERALITY; TOOLS AB This research examined hand preference for a bimanual task in 45 tufted capuchin (Cebus apella) and 55 rhesus macaque (Macaca mulatta) monkeys. Investigators presented subjects with plastic tubes lined with food and noted which hand the animals used to hold the tubes and which hand the animals used to remove the food. Several significant findings emerged from this investigation. First, rhesus macaques, but not tufted capuchins, exhibited a population-level bias toward use of the right hand (although the difference in direction of hand preference between species was not significant). Second, capuchins exhibited greater hand preference strength than did macaques. Third, among capuchins, but not among macaques, hand preference strength was greater for adults than for immatures. Finally, both species used their index digit to remove food most frequently when compared with other digits. Findings of hand preference direction and strength in this study were compared with other findings noted for chimpanzees which performed a bimanual tube task in a previous study. The authors conclude that using the same procedure to compare hand preference across species represents a powerful research tool that can lead to a more complete understanding of the evolution and ontogenesis of primate handedness. C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. NR 20 TC 74 Z9 74 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD DEC PY 1996 VL 110 IS 4 BP 406 EP 411 PG 6 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA VX907 UT WOS:A1996VX90700010 PM 8956511 ER PT J AU Ikeda, M Taga, M Sakakibara, H Minaguchi, H Ginsburg, E Vonderhaar, BK AF Ikeda, M Taga, M Sakakibara, H Minaguchi, H Ginsburg, E Vonderhaar, BK TI Gene expression of gonadotropin-releasing hormone in early pregnant rat and steroid hormone exposed mouse uteri SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE gene expression; GnRH; uterus; pregnancy ID MESSENGER-RIBONUCLEIC-ACID; HYPOTHALAMUS; PLACENTA AB While gonadotropin-releasing hormone (GnRH) or GnRH-like substance have been reported to exist in nonhypothalamic tissues such as placenta, gonads, and mammary gland, there have been no reports concerning the detection of GnRH mRNA in uterine tissue. In order to investigate the presence of GnRH in decidual tissues and its possible involvement in the regulation of placental function, we examined the gene for GnRH in the rodent uterus in early pregnancy and in nonpregnant animals treated with female sex steroids. Using RT-PCR and in situ hybridization we found GnRH mRNA transcripts in the rat uterus of 3- and 6- day gestation and in the mouse uterus treated with estrogen and progesterone. In situ hybridization revealed that GnRH mRNA was localized in the endometrial stromal cells of the 3rd and 6th day of gestation, These results suggest the existence of GnRH gene expression in uterine stromal cells and its possible paracrine effect derived from the decidual cells. (C) 1996, Editrice Kurtis. C1 NCI,NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD. RP Ikeda, M (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT OBSTET & GYNECOL,KANAGAWA KU,3-9 FUKUURA,YOKOHAMA,KANAGAWA 236,JAPAN. NR 21 TC 9 Z9 9 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD DEC PY 1996 VL 19 IS 11 BP 708 EP 713 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WF470 UT WOS:A1996WF47000001 PM 9061502 ER PT J AU Punt, JA Suzuki, H Granger, LG Sharrow, SO Singer, A AF Punt, JA Suzuki, H Granger, LG Sharrow, SO Singer, A TI Lineage commitment in the thymus: Only the most differentiated (TCR(hi)bcl-2(hi)) subset of CD4(+)CD8(+) thymocytes has selectively terminated CD4 or CD8 synthesis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; POSITIVE SELECTION; RECEPTOR EXPRESSION; BCL-2 EXPRESSION; LYMPHOCYTES-T; MATURATION; MICE; KINETICS; EVENTS; SIGNAL AB Lineage commitment is a developmental process by which individual CD4(+)CD8(+) (double positive, DP) thymocytes make a decision to differentiate into either CD4(+) or CD8(+) T cells. However, the molecular event(s) that defines lineage commitment is controversial. We have previously proposed that lineage commitment in DP thymocytes can be molecularly defined as the selective termination of CD4 or CD8 coreceptor synthesis. The present study supports such a molecular definition by showing that termination of either CD4 or CD8 synthesis is a highly regulated event that is only evident within the most differentiated DP subset (CD5(hi)CD69(hi)TCR(hi)bcl-2(hi)). In fact, essentially all cells within this DP subset actively synthesize only one coreceptor molecule. In addition, the present results identify three distinct subpopulations of DP thymocytes that define the developmental progression of the lineage commitment process and demonstrate that lineage commitment is coincident with upregulation of TCR and bcl-2. Thus, this study supports a molecular definition of lineage commitment and uniquely identifies TCR(hi)bcl-2(hi) DP thymocytes as cells that are already committed to either the CD4 or CD8 T cell lineage. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI Suzuki, Harumi/L-1271-2013 OI Suzuki, Harumi/0000-0003-3616-9361 FU NIAID NIH HHS [N01-AI72622] NR 33 TC 47 Z9 47 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 DEC 1 PY 1996 VL 184 IS 6 BP 2091 EP 2099 DI 10.1084/jem.184.6.2091 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300003 PM 8976166 ER PT J AU Sechler, JMG Lawler, A Hartley, JW Morse, HC McCarty, TC Swofford, R Rosenberg, AS AF Sechler, JMG Lawler, A Hartley, JW Morse, HC McCarty, TC Swofford, R Rosenberg, AS TI Induction of murine acquired immunodeficiency syndrome (MAIDS) in allophenic mice generated from strains susceptible and resistant to disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; LEUKEMIA VIRUSES; DEFECTIVE VIRUS; EXPRESSION; INFECTION; AIDS; IMMUNIZATION; ANTIBODY; SUBSET AB To examine whether a retroviral disease can be controlled in animals in which cells from a resistant strain coexist in a state of immunological tolerance with cells from a susceptible strain, allophenic mice were constructed and infected with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation and immunodeficiency in susceptible inbred strains of mice. We found that in two different strain combinations, resistance to MAIDS was contingent on the presence in individual animals of >50% of lymphocytes of resistant strain origin and correlated with reduction or elimination of retrovirus. In contrast, animals harboring substantial, but less than predominant, numbers of genetically resistant lymphocytes developed disease and died within the same time frame as susceptible control mice with uncontained proliferation of retrovirus. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21287. NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NIAID,MOL STRUCT LAB,FLOW CYMETRY SECT,NIH,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 NR 32 TC 0 Z9 0 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 DEC 1 PY 1996 VL 184 IS 6 BP 2101 EP 2108 DI 10.1084/jem.184.6.2101 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300004 PM 9005249 ER PT J AU Mason, LH Anderson, SK Yokoyama, WM Smith, HRC WinklerPickett, R Ortaldo, JR AF Mason, LH Anderson, SK Yokoyama, WM Smith, HRC WinklerPickett, R Ortaldo, JR TI The Ly-49D receptor activates murine natural killer cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IL-2-ACTIVATED NK CELLS; MULTIGENE FAMILY; MEMBRANE-PROTEINS; ANTIGEN; SUBSETS; MOUSE; MOLECULES; ADHESION; MEMBERS; CLONING AB Proteins encoded by members of the Ly-49 gene family are predominantly expressed on murine natural killer (NK) cells. Several members of this gene family have been demonstrated to inhibit NK cell lysis upon recognizing their class I ligands on target cells. In this report, we present data supporting that not all Ly-49 proteins inhibit NK cell function. Our laboratory has generated and characterized a monoclonal antibody (mAb) (12A8) that can be used to recognize the Ly-49D subset of murine NK cells. Transfection of Cos-7 cells with known members of the Ly-49 gene family revealed that 12A8 recognizes Ly-49D, but also cross-reacts with the Ly-49A protein on B6 NK cells. In addition, 12A8 demonstrates reactivity by both immunoprecipitation and two-color now cytometry analysis with an NK cell subset that is distinct from those expressing Ly-49A, C, or G2. An Ly-49D(+) subset of NK cells that did not express Ly-49A, C, and G2 was isolated and examined for their functional capabilities. Tumor targets and concanovalin A (ConA) lymphoblasts from a variety of H2 haplotypes were examined for their susceptibility to lysis by Ly-49D(+) NK cells. None of the major histocompatibility complex class I-bearing targets inhibited lysis of Ly-49D(+) NK cells. More importantly, we demonstrate that the addition of mAb 12A8 to Ly-49D(+) NK cells can augment lysis of Fc gamma R(+) target cells in a reverse antibody-dependent cellular cytotoxicity-type assay and induces apoptosis in Ly-49D(+) NK cells. Furthermore, the cytoplasmic domain of Ly-49D does not contain the V/Ix-YxxL immunoreceptor tyrosine-based inhibitory motif found in Ly-49A, C, or G2 that has been characterized in the human p58 killer inhibitory receptors. Therefore, Ly-49D is the first member of the Ly-49 family characterized as transmitting positive signals to NK cells, rather than inhibiting NK cell function. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. WASHINGTON UNIV,DIV RHEUMATOL,ST LOUIS,MO 63110. RP Mason, LH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,BLDG 560,ROOM 31-93,FREDERICK,MD 21702, USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 NR 24 TC 188 Z9 189 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 DEC 1 PY 1996 VL 184 IS 6 BP 2119 EP 2128 DI 10.1084/jem.184.6.2119 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300006 PM 8976168 ER PT J AU Wang, RF Appella, E Kawakami, Y Kang, XQ Rosenberg, SA AF Wang, RF Appella, E Kawakami, Y Kang, XQ Rosenberg, SA TI Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-MELANOMA; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; IMMUNE RECOGNITION; HLA-A2 MELANOMAS; TYROSINASE; CELLS; INTERLEUKIN-2; IMMUNOTHERAPY; PEPTIDE AB The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell Line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested. RP Wang, RF (reprint author), NCI,NIH,BLDG 10,2B42,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 46 TC 218 Z9 225 U1 1 U2 5 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 DEC 1 PY 1996 VL 184 IS 6 BP 2207 EP 2216 DI 10.1084/jem.184.6.2207 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300014 PM 8976176 ER PT J AU Borkowski, TA Letterio, JJ Farr, AG Udey, MC AF Borkowski, TA Letterio, JJ Farr, AG Udey, MC TI A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: The skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DENDRITIC CELLS; EXPRESSION; MOUSE; MACROPHAGE; RECEPTORS; ANTIGEN; RELB AB Transforming growth factor beta 1 (TGF-beta 1) regulates leukocytes and epithelial cells. To determine whether the pleiotropic effects of TGF-beta 1, a cytokine that is produced by both keratinocytes and Langerhans cells (LC), extend to epidermal leukocytes, we characterized LC (the epidermal contingent of the dendritic cell [DC] lineage) and dendritic epidermal T cells (DETC) in TGF-beta 1 null (TGF-beta 1 -/-) mice. I-A(+) LC were not detected in epidermal cell suspensions or epidermal sheets prepared from TGF-beta 1 -/- mice, and epidermal cell suspensions were devoid of allostimulatory activity. In contrast, TCR-gamma delta(+) DETC were normal in number and appearance in TGF-beta 1 -/- mice and, importantly, DETC represented the only leukocytes in the epidermis. Immunolocalization studies revealed CD11c(+)DC in lymph nodes from TGF-beta 1 -/- mice, although gp40(+) DC were absent. Treatment of TGF-beta 1 -/- mice with rapamycin abrogated the characteristic inflammatory wasting syndrome and prolonged survival indefinitely, but did not result in population of the epidermis with LC. Thus, the LC abnormality in TGF-beta 1 -/- mice is not a consequence of inflammation in skin or other organs, and LC development is not simply delayed in these animals. We conclude that endogenous TGF-beta 1 is essential for normal murine LC development or epidermal localization. C1 NCI,DERMATOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,NATL INST HLTH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195. FU NIA NIH HHS [AG 04350]; NIAID NIH HHS [AI 24137, R01 AI024137] NR 30 TC 340 Z9 348 U1 2 U2 12 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 DEC 1 PY 1996 VL 184 IS 6 BP 2417 EP 2422 DI 10.1084/jem.184.6.2417 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300035 PM 8976197 ER PT J AU Sarin, A Wu, ML Henkart, PA AF Sarin, A Wu, ML Henkart, PA TI Different interleukin-1 beta converting enzyme (ICE) family protease requirements for the apoptotic death of T lymphocytes triggered by diverse stimuli SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELLS; INHIBITOR AB Two cell permeable peptide fluoromethyl ketone inhibitors of Interleukin-1 beta converting enzyme (ICE) family proteases were tested as inhibitors of apoptotic cell death of T lymphocytes at various stages of differentiation. The CPP-32-like protease activity in apoptotic cell lysates was blocked by both the ICE inhibitor Cbz-Val-Ala-Asp (OMe)-fluoromethyl ketone (ZVAD-FMK) as well as its truncated analog Boc-Asp(OMe)-fluoromethyl ketone (BD-FMK), which failed to block ICE. In vitro apoptotic death in murine thymocytes triggered by the independent agents dexamethasone, etoposide, radiation, anti-Fas, and anti-CD3 was blocked equally well by BD-FMK and ZVAD-FMK, but not by the control reagent Cbz-Phe-Ala-fluoromethyl ketone. In activated T cell blasts, while anti-CD3/Fas-induced death was almost completely inhibited by both ZVAD-FMK and BD-FMK, death induced by dexamethasone, etoposide, or irradiation was more sensitive to inhibition by BD-FMK. In the murine T cell line CTLL-2, apoptotic death induced by IL-2 withdrawal, etoposide, or dexamethasone was inhibited by BD-FMK, while ZVAD-FMK was without effect. These data indicate that ICE-family proteases comprise a common functional step in distinct T cell apoptotic death pathways, but suggest that different family members are Likely to be critical in various differentiated T cell, types, even when triggered by the same stimulus. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 155 Z9 157 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 DEC 1 PY 1996 VL 184 IS 6 BP 2445 EP 2450 DI 10.1084/jem.184.6.2445 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VZ413 UT WOS:A1996VZ41300040 PM 8976202 ER PT J AU Briggs, CJ Tozser, J Oroszlan, S AF Briggs, CJ Tozser, J Oroszlan, S TI Effect of cyclosporin A on the replication cycle of human immunodeficiency virus type 1 derived from H9 and Molt-4 producer cells SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CYCLOPHILIN-A; NUCLEIC-ACIDS; HIV-1 VIRIONS; SDZ NIM-811; ASSOCIATION; INFECTION; INTERFERENCE; ACTIVATION; ISOMERASES; PROTEINS AB The effect of cyclosporin A (CsA) on the replication of human immunodeficiency virus type 1 (HIV-1) was studied. CsA treatment inhibited virus production in chronically infected H9 and Molt-4 cells. CsA treatment of HeLaCD4/LTR/beta-gal cells or extracellular viruses also inhibited infection (IC50 1 mu g/ml). The intracellular CsA-binding molecule cyclophilin A was detected in HIV-1 derived from chronically infected H9 cells, but it was present at a substantially lower level in HIV-1 derived from chronically infected Molt-4 cells. The low level of cyclophilin A in viral particles derived from Molt-4 cells correlated well with their substantially lower infectivity as assayed on HeLaCD4-LTR/beta-gal cells. CsA treatment of infected cells showed a dose-dependent reduction of cyclophilin A incorporation into virions; the amount of cyclophilin A incorporation was found to be dependent on the producer cell type. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. 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 NR 23 TC 9 Z9 9 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 1996 VL 77 BP 2963 EP 2967 DI 10.1099/0022-1317-77-12-2963 PN 12 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA WB251 UT WOS:A1996WB25100007 PM 9000086 ER PT J AU Jacobsen, K McGuire, TG AF Jacobsen, K McGuire, TG TI Federal block grants and state spending: The alcohol, drug abuse, and mental health block grant and state agency behavior SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Article ID EXPENDITURE; IMPACT AB With renewed interest in block grants as a way to channel federal funds to states, several questions arise about the effect of block grants on state spending. A central question about the block grant form of intergovernmental aid is whether states spend the funds on the intended services or use budgetary strategies to appear to be in compliance with maintenance-of-effort provisions but then reallocate block grant funds from the targeted program. We studied the effect of the Alcohol, Drug Abuse, and Mental Health block grant program on state substance abuse expenditures by analyzing spending data from the fifty states between fiscal years 1987 and 1992. Our findings suggest that this block grant has stimulated state spending, but this effect may be relevant only since 1990, and differs among states. C1 BOSTON UNIV,NIMH POLIT ECON STATE MENTAL HLTH AGCY PROJECT,BOSTON,MA 02215. RP Jacobsen, K (reprint author), REGIS COLL,WESTON,MA 02193, USA. FU NIMH NIH HHS [K05 MH01263, R01 MH49731] NR 22 TC 7 Z9 7 U1 1 U2 2 PU DUKE UNIV PRESS PI DURHAM PA BOX 90660, DURHAM, NC 27708-0660 SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD WIN PY 1996 VL 21 IS 4 BP 753 EP 770 PG 18 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA VL107 UT WOS:A1996VL10700003 PM 8892005 ER PT J AU Hunyady, B Krempels, K Harta, G Mezey, E AF Hunyady, B Krempels, K Harta, G Mezey, E TI Immunohistochemical signal amplification by catalyzed reporter deposition and its application in double immunostaining SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE immunohistochemistry; ABC technique; immunofluorescence technique; amplification; tyramine conjugates; rat; stomach; pancreas; hypothalamus; proton pump; pancreatic polypeptide; glucagon; neurofilament; tyrosine hydroxylase; oxytocin ID PANCREATIC-POLYPEPTIDE; BIOTIN AMPLIFICATION; ANTIBODIES AB The biotinyl-tyramide substrate of the horseradish peroxidase enzyme has been recently introduced to amplify immunohistochemical signals. We applied either fluorochrome- or biotin-conjugated tyramine to improve the detection of different antigens in sections of rat stomach, pancreas, and hypothalamus, A ten- to 100-fold increase in staining efficiency was achieved, depending on the antibody, with either fluorescent or peroxidase detection systems, The amplification method was particularly useful for increasing a weak signal of conventional immunostaining caused by suboptimal tissue fixation. At a very low concentration of the primary antibody, the antigen can no longer be detected by a conventional fluorescent secondary antibody but is still detectable after amplification, When an antibody is used at this very low concentration and is detected by a fluorescent amplification method, another primary antibody, raised in the same host species, can be used and demonstrated with a different fluorochrome in subsequent conventional immunostaining of the same section, In this way it becomes possible to immunostain the same section with two different primary antibodies raised in the same host species, Samples for such double immunostaining are demonstrated here using pairs of monoclonal antibodies (to tyrosine hydroxylase and oxytocin) in the hypothalamus and polyclonal antibodies (to glucagon and neurofilament M) in sections of rat pancreas, Because in many cases the availability of antibodies is limited, the amplification method can be a guide and efficient tool for double immunostaining with antibodies from the same host species. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. MED UNIV PECS,DEPT MED 1,PECS,HUNGARY. NR 16 TC 209 Z9 215 U1 1 U2 7 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1996 VL 44 IS 12 BP 1353 EP 1362 PG 10 WC Cell Biology SC Cell Biology GA VZ426 UT WOS:A1996VZ42600001 PM 8985127 ER PT J AU Tanner, VA Ploug, T TaoCheng, JH AF Tanner, VA Ploug, T TaoCheng, JH TI Subcellular localization of SV2 and other secretory vesicle components in PC12 cells by an efficient method of preembedding EM immunocytochemistry for cell cultures SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE synaptic vesicles; large dense-cored vesicles; synaptophysin; chromogranin A; tyrosine hydroxylase ID NEURO-ENDOCRINE CELLS; NERVE GROWTH-FACTOR; SYNAPTIC VESICLES; MICROSCOPIC LOCALIZATION; PHEOCHROMOCYTOMA CELLS; MEMBRANE-PROTEINS; CHROMOGRANIN-A; SYNAPTOPHYSIN; IDENTIFICATION; GLYCOPROTEIN AB We demonstrated the subcellular localization of SV2, a transmembrane protein associated with neuroendocrine secretory vesicles, in NGF-treated PC12 cells by preembedding EM immunocytochemistry (ICC), using a small gold probe followed by silver enhancement. The use of a multiwell chamber slide substantially improved the efficiency of the preembedding EM ICC procedures for cell cultures. The advantages and related caveats of this method ate discussed. SV2 was distinctly localized on dusters of synaptic vesicles and large dense-cored vesicles (LDCV). The distribution of SV2 on these two types of secretory vesicles was compared quantitatively to that of another secretory vesicle-associated transmembrane protein, synaptophysin. In cultures under similar experimental conditions, the ratio of SV2 vs synaptophysin ICC staining on synaptic vesicle clusters was about 1:1, whereas it was about 9:1 on LDCV membranes. Furthermore, whereas SV2 is localized on the membranes of the LDCVs, chromogranin A, an acidic protein in secretory granules, is dearly in the core of the LDCVs. This is the first demonstration of these two antigens in such dose (similar to 20 nm) yet distinct compartments within a single organelle. C1 NINCDS,ELECTRON MICROSCOPY FACIL,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,EDMNS,DIABET BRANCH,BETHESDA,MD 20892. NR 20 TC 39 Z9 39 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1996 VL 44 IS 12 BP 1481 EP 1488 PG 8 WC Cell Biology SC Cell Biology GA VZ426 UT WOS:A1996VZ42600014 PM 8985140 ER PT J AU Cutler, JA AF Cutler, JA TI High blood pressure and end-organ damage SO JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT Proceedings of the 16th Scientific Meeting of the International-Society-of-Hypertension CY JUN 23-27, 1996 CL GLASGOW, SCOTLAND SP Int Soc Hypertension DE review; hypertension; cardiovascular disease; epidemiology; risk; causal relationship ID CORONARY HEART-DISEASE; CAROTID ATHEROSCLEROSIS; RISK-FACTORS; STROKE; HYPERTENSION; PREVALENCE; TRIALS AB Background Findings from numerous epidemiologic and clinical studies worldwide attest to a strong, graded, consistent relationship between blood pressure level and cardiovascular-renal diseases, subclinical and clinical, nonfatal and fatal. Objective This review summarizes results from selected prospective observational studies, primarily from US populations, and from randomized clinical trials. Review Analyses from the Multiple Risk Factor Intervention Trial (MRFIT) subjects (middle-aged men) and the Framingham Heart Study (middle-aged and elderly men and women) clearly establish that systolic blood pressure is a more powerful predictor of cardiovascular events than diastolic pressure. Wherever the full range of blood pressure has been examined, for example for systolic pressure in the MRFIT subjects and for diastolic pressure in pooled data from nine epidemiologic studies, the associations for coronary heart disease and stroke are seen to extend over the whole range, including 'normotensive' levels. In MRFIT, this continuous relationship has also recently been shown for end-stage renal disease and both systolic and diastolic pressure. Data from Framingham document further associations with peripheral vascular disease, congestive heart failure, and both electrocardiographic and echocardiographic left ventricular hypertrophy. Several studies are now available demonstrating a relationship between hypertension and carotid wall intimal-medial thickness. Finally, the causal nature of the relationships with major cardiovascular events is supported by the results of 17 large-scale randomized trials of blood-pressure-lowering using primarily diuretic- and beta-blocker-based drug regimens. Conclusions These trials have demonstrated highly significant reductions in fatal and nonfatal stroke and major coronary heart disease. There are few trial data, however, on health benefits from further reducing blood pressure among normotensive persons. RP Cutler, JA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,ROCKLEDGE CTR 2,6701 ROCKLEDGE DR,MSC 7936,BETHESDA,MD 20892, USA. NR 24 TC 17 Z9 17 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 1996 VL 14 SU 6 BP S3 EP S6 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WE739 UT WOS:A1996WE73900002 PM 9023707 ER PT J AU Cho, SS Bacon, CM Sudarshan, C Rees, RC Finbloom, D Pine, R OShea, JJ AF Cho, SS Bacon, CM Sudarshan, C Rees, RC Finbloom, D Pine, R OShea, JJ TI Activation of STAT4 by IL-12 and IFN-alpha - Evidence for the involvement of ligand-induced tyrosine and serine phosphorylation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATED-GENE FACTOR-3; SIGNAL-TRANSDUCTION; GAMMA-INTERFERON; PROTEIN-KINASE; TRANSCRIPTION FACTORS; BINDING PROTEIN; RESPONSE FACTOR; KILLER CELLS; INTERLEUKIN-12; RECEPTOR AB The immunoregulatory cytokine IL-12 plays a central role in cell-mediated immune responses through its effects on NK cells and T lymphocytes. While IL-12 is known to share some functions with other cytokines, such as IFN-LU, it also maintains distinct roles, such as its ability to induce Th1 differentiation, The molecular basis for these unique and overlapping functions is not well understood, IL-12 has previously been shown to induce tyrosine phosphorylation and DNA-binding of STAT3 and STAT4, members of the signal transducers and activators of transcription (STAT) family, Because STAT4 has only been shown to be activated in response to IL-12, this specificity has been suggested to be a basis for the unique actions of IL-12, In this study, we demonstrated that STAT4 activation by IL-12 is not unique; IL-12 and IFN-alpha, but not IFN-gamma, induced tyrosine phosphorylation and DNA binding of STAT4, Since tyrosine and serine phosphorylation of STAT1 have previously been shown to be important in IFN-alpha-mediated signaling, we also investigated IL-12- and IFN-alpha-induced serine phosphorylation of STAT4, We demonstrated that both cytokines induced serine phosphorylation, This modification was not required for DNA binding, but may be important in STAT-mediated transcription, Thus, STAT4 activation was not IL-12 specific, and IL-12 and IFN-alpha activated STAT4 through both tyrosine and serine phosphorylation. These findings have significant implications for understanding the role of STAT4 in mediating biologic functions; specifically, the data argue that the unique effects of IL-12 cannot be solely explained by STAT4 activation. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD,S YORKSHIRE,ENGLAND. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. PUBL HLTH RES INST,NEW YORK,NY 10016. NR 61 TC 205 Z9 210 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1996 VL 157 IS 11 BP 4781 EP 4789 PG 9 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100006 PM 8943379 ER PT J AU Fowler, DH Breglio, J Nagel, G Eckhaus, MA Gress, RE AF Fowler, DH Breglio, J Nagel, G Eckhaus, MA Gress, RE TI Allospecific CD8(+) Tc1 and Tc2 populations in graft-versus-leukemia effect and graft-versus-host disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; T-CELLS; IN-VIVO; MEDIATED CYTOTOXICITY; FAS; CYTOKINES; INTERLEUKIN-7; LYMPHOCYTES; PROFILES AB Allogeneic CD8(+) T cells mediate both a graft-vs-leukemic (GVL) effect and graft-vs-host disease (GVHD). To evaluate whether CD8 cells of defined cytokine phenotype differentially mediate these processes, alloreactive donor CD8(+) T cells preferentially secreting type I or type II cytokines were generated by alloantigenic priming in vitro in the presence of IL-12 or IL-4, respectively. Both cytokine-secreting subsets lysed allogeneic tumor targets in vitro (''Tc1'' and ''Tc2'' subsets). A transplantation model was established (B6 into B6C3F(nu) 1050 cGy host irradiation) using the 32Dp210 myeloid line (bcr/abl transfected, H-2(k); 1 x 10(4) tumor cells/recipient). Compared with leukemia controls (death at 12.9 days post-bone marrow transplantation), both Tc1 and Tc2 recipients were conferred a survival advantage. At cell doses of 2 to 2.5 x 10(7), the Tc1-mediated GVL effect (mean survival of 34.2 days) was more potent than the Tc2-mediated GVL effect (mean survival of 20.5 days; Tc1 > Tc2, p = 0.009). On day 15, histologic examination showed that Tc1 recipients had undetectable tumor burdens, whereas Tc2 recipients had extensive leukemic infiltrates. However, Tc2 recipients had essentially no histologic evidence of GVHD, whereas Tc1 recipients had mild to moderate GVHD (average GVHD scores of 1/40 and 9.3/40, respectively). In contrast, recipients of uncultured CD8(+) donor T cells developed severe GVHD (average GVHD score of 26.7/40). Because in vitro-generated, alloreactive Tc1 and Tc2 populations mediated GVL with reduced GVHD, we conclude that both subsets may improve the therapeutic outcome of allogeneic T cell transfers in patients with leukemia. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP Fowler, DH (reprint author), NCI,TRANSPLANTAT THERAPY SECT,NIH,MED ONCOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 50 TC 99 Z9 103 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1996 VL 157 IS 11 BP 4811 EP 4821 PG 11 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100010 PM 8943383 ER PT J AU Zamorano, J Wang, HY Wang, LM Pierce, JH Keegan, AD AF Zamorano, J Wang, HY Wang, LM Pierce, JH Keegan, AD TI Il-4 protects cells from apoptosis via the insulin receptor substrate pathway and a second independent signaling pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESTING B-CELLS; P70 S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; T-CELLS; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; FACTOR-I; STIMULATING FACTOR; INDUCE DEATH; ACTIVATION AB Although it has been known for some time that IL-4 protects cells from death via apoptosis, very little is known about the mechanism by which IL-4 exerts this effect, In this report, we have studied the molecular mechanisms of the IL-4-induced prevention of apoptosis in the 32D and B cell systems. IL-3 withdrawal has been shown to induce G1-arrest in 32D cells and subsequent death by apoptosis, We found that overexpression of IRS-1 protected 32D cells from death induced by IL-3 deprivation, IL-4 was able to protect: 32D cells from apoptosis in the presence or absence of IRS-1. However, the protection from apoptosis of cells cultured in IL-4 was greater in the presence of IRS-1 and it reached levels comparable to those of cells cultured in IL-3. The IRS-1-dependent prevention of apoptosis is linked to the activation of PI 3'-kinase since wortmannin and LY294002, two inhibitors of PI3'-K, partially inhibited the prevention of apoptasis mediated by IL-4 in 32D-IRS-1 cells after IL-3 withdrawal but not in 32D cells lacking IRS-1 expression, In addition, we found that the IRS/PI 3'-K pathway is, at least in part, responsible for the prevention of apoptosis by IL-4 in normal splenic B cell cultures. In spite of the ability of murine IL-4 to partially protect 32D cells lacking IRS-I from apoptosis, human IL-4 was not able to prevent cell death in 32D-lRS-1 cells transfected with the human IL-4 receptor mutated in the insulin-IL-4 receptor motif (14R-motif) at amino acid 497 (Y497F), This mutation has previously been shown to abrogate the tyrosine phosphorylation of IRS-1 by human IL-4. These results demonstrate that IL-4 protects 32D cells from apoptosis by two different pathways, one of them mediated by IRS-I, In addition, these results suggest that the 14R-motif of the IL-4R is linked to both pathways. C1 AMER RED CROSS,JEROME H HOLLAND LAB BIOMED SCI,DEPT IMMUNOL,ROCKVILLE,MD 20855. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-38985] NR 61 TC 118 Z9 119 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1996 VL 157 IS 11 BP 4926 EP 4934 PG 9 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100024 PM 8943397 ER PT J AU Thornton, AM Ogryzko, VV Dent, A Sharf, R Levi, BZ Kanno, Y Staudt, LM Howard, BH Ozato, K AF Thornton, AM Ogryzko, VV Dent, A Sharf, R Levi, BZ Kanno, Y Staudt, LM Howard, BH Ozato, K TI A dominant negative mutant of an IFN regulatory factor family protein inhibits both type I and type II IFN-stimulated gene expression and antiproliferative activity of IFNs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; MANGANESE SUPEROXIDE-DISMUTASE; MURINE PERITONEAL-MACROPHAGES; TRANSCRIPTION FACTOR ISGF3; INTERFERON-GAMMA; CELL-CYCLE; RETINOBLASTOMA PROTEIN; MESSENGER-RNA; GROWTH-SUPPRESSOR; INDUCIBLE GENE AB Type I (alpha, beta) and type II (gamma) IFNs elicit antiproliferative and antiviral activities through two distinct transcription pathways involving 1) IRF family proteins and ISGF3, and 2) STAT1. We have employed a dominant negative strategy to study the role of IRF family proteins in eliciting the biologic activities of IFN, A truncated IRT: protein retaining the DNA-binding domain (DBD) of ICSBP (a member of the IRF family) was stably transfected into U937 monocytic cells, Clones expressing DBD had markedly reduced ISRE-binding activity and were defective in expressing several type I IFN-inducible genes, STAT1 was one such type I IFN-inducible gene whose expression was also inhibited in DBD clones, As a result, the expression of several IFN-gamma-inducible genes was also inhibited in these clones, indicating functional coupling of the type I and type II IFN transcription pathways. Furthermore, DBD clones grew more slowly than control clones and were refractory to antiproliferative effects of both types of IFNs, We found that IFN treatment of U937 cells leads to a G1 arrest and an increase in underphosphorylated retinoblastoma gene product, However, IFN treatment did not change the cell cycle profile, nor retinoblastoma gene product phosphorylation state in DBD clones, These data indicate that expression of DBD disrupts cell cycle regulatory mechanisms, Combined with the previously noted failure of DBD clones to elicit antiviral activity, the present work shows that IRF family proteins play an integral part in growth control activities of IFNs. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,HAIFA,ISRAEL. RI Kanno, Yuka/B-5802-2013; Ogryzko, Vasily/M-6665-2015; OI Ogryzko, Vasily/0000-0002-8548-1389; Kanno, Yuka/0000-0001-5668-9319 NR 58 TC 21 Z9 21 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 DEC 1 PY 1996 VL 157 IS 11 BP 5145 EP 5154 PG 10 WC Immunology SC Immunology GA VU501 UT WOS:A1996VU50100053 PM 8943426 ER PT J AU Kimberlin, DW Lakeman, FD Arvin, AM Prober, CG Corey, L Powell, DA Burchett, SK Jacobs, RF Starr, SE Whitley, RJ Soong, SJ Stagno, S Pass, R Robinson, J Vaudry, W Jacobs, R Arvin, A Prober, C Bradley, J Spector, S Kovacs, A Bryson, Y Rathore, M Reuman, P Keyserling, H Diaz, P Bale, J Laudert, S Steele, R vanDyke, R Laughlin, C Burchett, S Meissner, C deSierra, M Kinney, J Storch, G Modlin, J Weiner, L Leistikow, E McKinney, R Kumar, M Powell, D Stanberry, L Gruber, W Sander, C Demmler, G Chonmaitree, T Leach, C Shelton, M Adler, S Corey, L Gross, J AF Kimberlin, DW Lakeman, FD Arvin, AM Prober, CG Corey, L Powell, DA Burchett, SK Jacobs, RF Starr, SE Whitley, RJ Soong, SJ Stagno, S Pass, R Robinson, J Vaudry, W Jacobs, R Arvin, A Prober, C Bradley, J Spector, S Kovacs, A Bryson, Y Rathore, M Reuman, P Keyserling, H Diaz, P Bale, J Laudert, S Steele, R vanDyke, R Laughlin, C Burchett, S Meissner, C deSierra, M Kinney, J Storch, G Modlin, J Weiner, L Leistikow, E McKinney, R Kumar, M Powell, D Stanberry, L Gruber, W Sander, C Demmler, G Chonmaitree, T Leach, C Shelton, M Adler, S Corey, L Gross, J TI Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CEREBROSPINAL-FLUID; VIDARABINE THERAPY; RAPID DIAGNOSIS; REACTION ASSAY; ENCEPHALITIS; INFECTION; DNA AB Cerebrospinal fluid (CSF) specimens from 77 neonates with herpes simplex virus (HSV) disease were evaluated retrospectively by polymerase chain reaction (PCR), Samples were collected from 202 infants enrolled in a National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial that compared vidarabine with acyclovir for the treatment of neonatal HSV infection, HSV DNA was detected in the CSF of 26 (76%) of 34 infants with CNS disease, in 13 (93%) of 14 infants with disseminated infection, and in 7 (24%) of 29 with skin, eye, or mouth (SEM) involvement. One of the 7 PCR-positive SEM patients subsequently developed severe neurologic impairment, Eighteen (95%) of 19 infants with positive CSF PCR results after the completion of 10 days of antiviral therapy experienced significant morbidity or mortality, Application of PCR to neonatal HSV disease may provide additional information on which clinical decisions may be based, although its diagnostic utility outside the research setting is unproven. C1 UNIV ALABAMA, DEPT MICROBIOL, BIRMINGHAM, AL 35233 USA. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35233 USA. STANFORD UNIV, DEPT PEDIAT, STANFORD, CA 94305 USA. UNIV WASHINGTON, DEPT MED, SEATTLE, WA USA. OHIO STATE UNIV, DEPT PEDIAT, COLUMBUS, OH 43210 USA. UNIV ARKANSAS, DEPT PEDIAT, LITTLE ROCK, AR 72204 USA. JOSEPH STOKES JR RES INST, DEPT PEDIAT, PHILADELPHIA, PA USA. UNIV ALBERTA, EDMONTON, AB, CANADA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. UNIV FLORIDA, GAINESVILLE, FL USA. EMORY UNIV, ATLANTA, GA 30322 USA. CHICAGO DEPT PUBL HLTH, CHICAGO, IL USA. UNIV IOWA, IOWA CITY, IA USA. HCA WESLEY MED CTR, WICHITA, KS USA. LOUISIANA STATE UNIV, NEW ORLEANS, LA 70112 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. NIH, BETHESDA, MD 20892 USA. CHILDRENS HOSP, BOSTON, MA 02115 USA. TUFTS UNIV NEW ENGLAND MED CTR, BOSTON, MA 02111 USA. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ, MEXICO CITY, DF, MEXICO. UNIV MISSOURI, KANSAS CITY, MO 64110 USA. WASHINGTON UNIV, MED CTR, ST LOUIS, MO USA. DARTMOUTH HITCHCOCK MED CTR, LEBANON, NH 03766 USA. SUNY SYRACUSE, HLTH SCI CTR, SYRACUSE, NY 13210 USA. COASTAL AREA HLTH EDUC CTR, WILMINGTON, NC USA. DUKE UNIV, DURHAM, NC USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. UNIV CINCINNATI, CINCINNATI, OH 45221 USA. CHILDRENS HOSP PHILADELPHIA, PHILADELPHIA, PA 19104 USA. VANDERBILT UNIV, NASHVILLE, TN USA. BAPTIST MEM CTR E, MEMPHIS, TN USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. UNIV TEXAS SAN ANTONIO, MED BRANCH, GALVESTON, TX 77550 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. COOK CHILDRENS MED CTR, FT WORTH, TX USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, RICHMOND, VA 23298 USA. MARSHFIELD MED RES FDN, MARSHFIELD, WI 54449 USA. RP Kimberlin, DW (reprint author), UNIV ALABAMA, DEPT PEDIAT, 1600 7TH AVE S, SUITE 616, BIRMINGHAM, AL 35233 USA. FU NCRR NIH HHS [RR-032]; NIAID NIH HHS [AI-15113, AI-62554] NR 19 TC 116 Z9 119 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 DEC PY 1996 VL 174 IS 6 BP 1162 EP 1167 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200003 PM 8940204 ER PT J AU Sei, S Stewart, SK Farley, M Mueller, BU Lane, JR Robb, ML Brouwers, P Pizzo, PA AF Sei, S Stewart, SK Farley, M Mueller, BU Lane, JR Robb, ML Brouwers, P Pizzo, PA TI Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; AIDS DEMENTIA COMPLEX; PLATELET-ACTIVATING-FACTOR; POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; NEUROLOGICAL DISEASE; CONTINUOUS-INFUSION; QUINOLINIC ACID; NITRIC-OXIDE; INFECTION AB The amount of human immunodeficiency virus (HIV) type 1 RNA and the presence of a codon 215 mutation indicative of zidovudine resistance were evaluated in cerebrospinal fluid (CSF) and plasma obtained from HIV-1-infected children, The level of HIV-1 RNA in CSF was highest in children with severe encephalopathy (n = 25; median, 430 copies/mL; range, 0-2.2 x 10(5) copies/mL) followed by the moderately encephalopathic (n = 7; median, 330; range, 0-1130) and nonencephalopathic groups (n = 9; median, 0; range, 0-566) (P = .007), There was no correlation between CSF and plasma HIV-1 RNA levels. Five of 7 children with the codon 215 mutation in CSF had a progression of encephalopathy, while all 8 children with wild type codon 215 had improved or stable disease during zidovudine treatment (P = .007), These findings suggest that increased viral replication and emergence of drug-resistant HIV-1 variants within the central nervous system may play a role in progression of HIV encephalopathy. C1 SRA TECHNOL INC,ROCKVILLE,MD. WALTER REED ARMY INST RES,DEPT RETROVIRAL RES,ROCKVILLE,MD. RP Sei, S (reprint author), NCI,PEDIAT BRANCH,DIV CLIN SCI,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC1928,BETHESDA,MD 20892, USA. NR 44 TC 60 Z9 61 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1996 VL 174 IS 6 BP 1200 EP 1206 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200008 PM 8940209 ER PT J AU Cooper, ER Nugent, RP Diaz, C Pitt, J Hanson, C Kalish, LA Mendez, H Zorrilla, C Hershow, R Moye, J Smeriglio, V Fowler, MG Rich, K Turpin, D PachecoAcosta, E Tuomala, R Mesthene, D Fox, H Higgins, A Landesman, S Moroso, G Willoughby, A Sheon, A McKinlay, S Sherrieb, K AF Cooper, ER Nugent, RP Diaz, C Pitt, J Hanson, C Kalish, LA Mendez, H Zorrilla, C Hershow, R Moye, J Smeriglio, V Fowler, MG Rich, K Turpin, D PachecoAcosta, E Tuomala, R Mesthene, D Fox, H Higgins, A Landesman, S Moroso, G Willoughby, A Sheon, A McKinlay, S Sherrieb, K TI After AIDS clinical trial 076: The changing pattern of zidovudine use during pregnancy, and the subsequent reduction in the vertical transmission of human immunodeficiency virus in a cohort of infected women and their infants SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIV-1 INFECTION; TYPE-1; RISK AB To determine the impact of the AIDS Clinical Trials Group (ACTG) Protocol 076 results on the subsequent use of zidovudine during pregnancy and the transmission rate of human immunodeficiency virus (HIV) in a cohort of mother-infant pairs (Women and Infants Transmission Study), a retrospective analysis was done, Transmission rates were calculated by simple proportion for infants with at least 6 months of follow-up, stratified by date of birth (n = 453 born on or before 1 March 1994; n = 103 born after 1 March 1994), Transmission rates decreased from 19% to 8% (P = .005, Fisher's exact test), Zidovudine use increased during pregnancy (22% vs, 89%) and in newborns (1% vs, 79%), Both cohorts were similar with respect to maternal immunosuppression, mode of delivery, and demographics, In summary, in a perinatal HIV observational study, the release of results of ACTG Protocol 076 was associated with an increase in zidovudine use during pregnancy and a concomitant decline in HIV transmission from mothers to infants. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. NICHHD,NIH,BETHESDA,MD 20892. NIDA,NIH,BETHESDA,MD. NIAID,NIH,BETHESDA,MD 20892. UNIV PUERTO RICO,SAN JUAN,PR 00936. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV ILLINOIS,CHICAGO,IL. RP Cooper, ER (reprint author), BOSTON UNIV,BOSTON CITY HOSP,SCH MED,818 HARRISON AVE,FINLAND 506,BOSTON,MA 02118, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [AI-34856]; NICHD NIH HHS [HD-43208] NR 19 TC 105 Z9 107 U1 0 U2 3 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 DEC PY 1996 VL 174 IS 6 BP 1207 EP 1211 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200009 PM 8940210 ER PT J AU Yanagi, M Bukh, J Emerson, U Purcell, RH AF Yanagi, M Bukh, J Emerson, U Purcell, RH TI Contamination of commercially available fetal bovine sera with bovine viral diarrhea virus genomes: Implications for the study of hepatitis C virus in cell cultures SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID 5' UNTRANSLATED REGION; NUCLEOTIDE-SEQUENCE; RNA; IDENTIFICATION; LINE AB The establishment of cell cultures for hepatitis C virus (HCV) is important for its study as a human pathogen. However, in reported cell lines, HCV demonstrates low levels of replication detected primarily by reverse transcription-polymerase chain reaction (RT-PCR) assays, In attempts to culture HCV, an additional complication was observed, From mock-infected cultures, cDNA of appropriate size was obtained by RT-PCR with primers deduced from conserved domains of the 5' noncoding region of HCV. However, sequence analysis revealed that the cDNA was amplified from bovine viral diarrhea virus (BVDV). All of 7 bovine sera tested were contaminated with BVDV, In conclusion, most commercially available bovine sera are contaminated with BVDV and, although there is no evidence that the virus is infectious, bovine sera should be screened for this virus by RT-PCR when used in conjunction with HCV or for the development or production of vaccine. C1 NIAID,NIH,LID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NR 13 TC 36 Z9 37 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 DEC PY 1996 VL 174 IS 6 BP 1324 EP 1327 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200025 PM 8940226 ER PT J AU McCarthy, JS Nutman, TB AF McCarthy, JS Nutman, TB TI Perspective: Prospects for development of vaccines against human helminth infections SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ONCHOCERCA-VOLVULUS INFECTION; SCHISTOSOMA-MANSONI CERCARIAE; PROTECTIVE IMMUNITY; BRUGIA-PAHANGI; PUTATIVELY IMMUNE; TRICHURIS-TRICHIURA; DIROFILARIA-IMMITIS; DIPETALONEMA-VITEAE; RECOMBINANT ANTIGEN; ENDEMIC FILARIASIS RP McCarthy, JS (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 88 TC 13 Z9 13 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 DEC PY 1996 VL 174 IS 6 BP 1384 EP 1390 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VV272 UT WOS:A1996VV27200040 PM 8940241 ER PT J AU JezowskaBojczuk, M Bal, W Kasprzak, KS AF JezowskaBojczuk, M Bal, W Kasprzak, KS TI Copper(II) interactions with an experimental antiviral agent, 1-deoxynojirimycin, and oxygen activation by resulting complexes SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article ID D-GLUCOSAMINE; DERIVATIVES; DNA; DEOXYNOJIRIMYCIN; DEOXYGUANOSINE; HYDROXYLATION; NICKEL(II); ANALOGS; IONS AB 1-deoxynojirimycin (DNJ), a 5-imino analog of 1-deoxyglucose, is a potent inhibitor of alpha-glucosidase I. DNJ and its derivatives have been considered as experimental drugs against human HIV-1 and hepatitis B viruses. Since amino and imino ligands have a high affinity for copper, it seems possible that biological activity of DNJ may be, at least in part, modulated by tissue copper. To test this possibility, potentiometric and spectroscopic studies of the complexation of DNJ by cupric ions were performed in order to obtain thermodynamic and structural background for further pharmacologic investigations. The effect of histidine, a major tissue copper carrier, on coordination equilibria was also studied. Results indicate that DNJ and Cu(II) form two stable complexes at physiological pH, CuH-1(DNJ)(2)(+) and CuH-2(DNJ)(2), involving Cu(II) chelation by the N-5 and O-6 donor atoms. In the presence of histidine, ternary complexes are also formed, of which the CuDNJHis(+) species is stable in the physiological pH range. Binary Cu(II)-DNJ complexes are extremely effective mediators of in vitro oxidation of the guanine moiety in both 2'-deoxyguanosine (dG) and DNA to 8-oxoguanine (8-oxo-dG) and of DNA double strand scission by ambient O-2 or H2O2. This mediation is suppressed by histidine in dG, but not in DNA. The results suggest that tissue Cu(II) may greatly enhance nonspecific cytotoxic effects of systemically administered DNJ through oxidative damage mechanisms, and therefore the prospective use of DNJ for therapeutic purposes must be developed with caution. On the other hand, however, the expected high genotoxic potential of synthetic Cu(II)-DNJ complexes may be used against viruses by means of targeted delivery of these complexes to the infected cells. (C) 1996 Elsevier Science Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 29 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD DEC PY 1996 VL 64 IS 4 BP 231 EP 246 DI 10.1016/S0162-0134(96)00051-7 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA VR397 UT WOS:A1996VR39700001 PM 8916412 ER PT J AU Sopko, G AF Sopko, G TI Clinical and economic issues of coronary interventions: Quo Vadis 1990s SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ARTERY BYPASS-SURGERY; ISCHEMIA PILOT ACIP; NEW-YORK-STATE; RANDOMIZED TRIAL; MEDICAL THERAPY; COMPLETE REVASCULARIZATION; PLASMINOGEN-ACTIVATOR; IMMEDIATE ANGIOPLASTY; THROMBOLYTIC THERAPY RP Sopko, G (reprint author), NHLBI,DIV HEART & VASC DIS,INTERVENT CARDIOL HEART RES PROGRAM,2 ROCKLEDGE CTR,STE 9044,BETHESDA,MD 20892, USA. NR 69 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD DEC PY 1996 VL 9 IS 6 BP 485 EP 494 DI 10.1111/j.1540-8183.1996.tb00663.x PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VZ506 UT WOS:A1996VZ50600011 ER PT J AU Bale, SJ Russell, LJ Lee, ML Compton, JG DiGiovanna, JJ AF Bale, SJ Russell, LJ Lee, ML Compton, JG DiGiovanna, JJ TI Congenital recessive ichthyosis unlinked to loci for epidermal transglutaminases SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE genodermatosis; linkage; genetics; heterogeneity ID LAMELLAR ICHTHYOSIS; TISSUE TRANSGLUTAMINASE; LINKAGE; HETEROGENEITY AB Congenital recessive ichthyosis has a broad range of clinical presentations, which may be considered a spectrum of phenotypes with classic lamellar ichthyosis at one pole and classic congenital ichthyosiform erythroderma at the other. The identification of mutations in the transglutaminase-1 gene as a cause of lamellar ichthyosis implicates transglutaminases in other congenital recessive ichthyoses. We investigated two multiplex families with clinical manifestations between the two poles for linkage to the transglutaminase-1 locus on chromosome 14. Strongly negative lod scores prompted a search for linkage to two other epidermally expressed transglutaminases, transglutaminase-2 and transglutaminase-1, on chromosome 20. No evidence for linkage was found. These data confirm the hypothesis that the congenital recessive ichthyoses are genetically heterogeneous and in two families exclude two other transglutaminases that could be considered as candidate loci for at least some of the nonlamellar recessive ichthyoses. C1 NIAMSD,DERMATOL CLIN RES UNIT,INTRAMURAL RES PROGRAM,NIH,BETHESDA,MD 20892. RP Bale, SJ (reprint author), NIAMSD,SKIN BIOL LAB,GENET STUDIES SECT,NIH,BLDG 6,ROOM 429,6 CTR DR,MSC 2757,BETHESDA,MD 20892, USA. RI Lee, Minjoo/A-9720-2008 OI Lee, Minjoo/0000-0002-3151-3808 NR 19 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1996 VL 107 IS 6 BP 808 EP 811 DI 10.1111/1523-1747.ep12330566 PG 4 WC Dermatology SC Dermatology GA VV220 UT WOS:A1996VV22000003 PM 8941665 ER PT J AU Richard, G Itin, P Lin, JP Bon, A Bale, SJ AF Richard, G Itin, P Lin, JP Bon, A Bale, SJ TI Evidence for genetic heterogeneity in monilethrix SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE hair; alopecia; keratin intermediate filaments; keratin intermediate filament-associated protein; trichohyalin; transglutaminase ID KERATIN GENE; LINKAGE; CLUSTER; 12Q13 AB Monilethrix is a rare inherited defect of the hair shaft resulting in hair fragility and dystrophic alopecia. In contrast to recent reports mapping monilethrix to the type II epithelial and trichocyte keratin gene cluster on 12q13, we strongly excluded these candidate genes in another family with autosomal dominant monilethrix, Moreover, there was no evidence for linkage of the disease to the keratin gene cluster on chromosome 17q12-q21, thus excluding defects in all known trichocyte and epithelial keratins as the cause of monilethrix in this family, Likewise, several other genes known to play an important role in hair shaft formation (trichohyalin and involucrin, ultra-high sulfur matrix proteins, and transglutaminases 1, 2, and 3) did not provide any evidence for linkage. Our results indicate genetic heterogeneity in monilethrix and suggest that aberrations in at least one other gene result in a similar phenotype. C1 UNIV BASEL,DEPT DERMATOL,BASEL,SWITZERLAND. RP Richard, G (reprint author), NIAMS,GENET STUDIES SECT,SKIN BIOL LAB,NIH,BLDG 6,ROOM 429,6 CTR DR,MSC 2757,BETHESDA,MD 20892, USA. NR 32 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1996 VL 107 IS 6 BP 812 EP 814 DI 10.1111/1523-1747.ep12330568 PG 3 WC Dermatology SC Dermatology GA VV220 UT WOS:A1996VV22000004 PM 8941666 ER PT J AU Ramanathan, KV Suryaprakash, N Khetrapal, CL Becker, ED Eichele, K Wasylishen, RE AF Ramanathan, KV Suryaprakash, N Khetrapal, CL Becker, ED Eichele, K Wasylishen, RE TI C-13 MAS NMR spectra of cis,cis-mucononitrile in liquid-crystalline media and in the solid state. Orientation of the carbon chemical-shift tensors SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID MAGIC ANGLE; MACROSCOPIC ROTATION; ORIENTED MOLECULES; NEMATIC DIRECTOR; SHIELDING SCALE; BEHAVIOR; SAMPLES; SIGNS AB The spinning sidebands observed in the C-13 MAS NMR spectra of cis,cis-mucononitrile oriented in liquid-crystalline media and of the neat sample in the solid state are studied. There are differences in the sideband intensity patterns in the two cases. These differences arise because the order parameters which characterize the orientation of the solute in the liquid-crystalline media differ for different axes. It is shown that, in general, the relative intensities of the sidebands contain information on the sign and magnitude of an effective chemical-shift parameter which is a function of the sum of the products of the principal components of the chemical-shift tensor and the corresponding order parameters with respect to the director. A method for obtaining the orientation of the carbon chemical-shift tensor is proposed. The carbon chemical-shift tensors obtained from gauge-including atomic orbital calculations are also presented for comparison. (C) 1996 Academic Press, Inc. C1 NIH,BETHESDA,MD 20892. DALHOUSIE UNIV,DEPT CHEM,HALIFAX,NS B3H 4J3,CANADA. RP Ramanathan, KV (reprint author), INDIAN INST SCI,SOPHISTICATED INSTRUMENTS FACIL,BANGALORE 560012,KARNATAKA,INDIA. OI Eichele, Klaus/0000-0002-9318-5782 NR 26 TC 2 Z9 2 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 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD DEC PY 1996 VL 123 IS 2 BP 196 EP 200 DI 10.1006/jmra.1996.0235 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA WA848 UT WOS:A1996WA84800008 ER PT J AU Acevedo, LD Xu, YD Zhang, X Pearce, RJ Yergey, A AF Acevedo, LD Xu, YD Zhang, X Pearce, RJ Yergey, A TI Quantification of acetylcholine in cell culture systems by semi-micro high-performance liquid chromatography and electrospray ionization mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE acetylcholine; liquid chromatography mass spectrometry; neurotransmitter release; cell culture ID CHOLINE-ACETYLTRANSFERASE; NEURONAL TISSUE; STORAGE; RELEASE; LINE; HPLC; PC12 AB Electrospray ionization (ESI) was used to adapt the thermospray ionization liquid chromatographic/mass spectrometric (LC/MS) method of Liberate et al. to the determination of acetylcholine and choline released from cells in culture. A clonal cell line derived from a rat pheochromocytoma (PC12) was used and cultures depolarized in the presence of cholinesterase inhibitor to maximize the recovery of acetylcholine from the culture medium and protect against its hydrolysis. Concentration of acetylcholine and choline released into the incubation medium was accomplished with Sep-Pak C-18 cartridges. The preformed analyte cations were resolved by reversed-phase high-performance liquid chromatography and analyzed without derivatization by electrospray ionization mass spectrometry with the use of acetyl[H-2(9)]choline as internal standard. LC/MS allows for the direct determination of acetylcholine and choline, which is not possible with other methods. C1 NICHHD,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 20 TC 16 Z9 16 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD DEC PY 1996 VL 31 IS 12 BP 1399 EP 1402 DI 10.1002/(SICI)1096-9888(199612)31:12<1399::AID-JMS439>3.3.CO;2-P PG 4 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA WA546 UT WOS:A1996WA54600009 PM 8990522 ER PT J AU Kubota, T Aradhya, S Macha, M Smith, ACM Surh, LC Satish, J Verp, MS Nee, HL Johnson, A Christian, SL Ledbetter, DH AF Kubota, T Aradhya, S Macha, M Smith, ACM Surh, LC Satish, J Verp, MS Nee, HL Johnson, A Christian, SL Ledbetter, DH TI Analysis of parent of origin specific DNA methylation at SNRPN and PW71 in tissues: Implication for prenatal diagnosis SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE SNRPN methylation; PW71 methylation; Prader-Willi/Angelman syndromes; prenatal diagnosis ID PRADER-WILLI-SYNDROME; MOLECULAR DIAGNOSIS; UNIPARENTAL DISOMY; ANGELMAN SYNDROMES; REGION; 15Q11-13; DEFINE AB Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct developmental disorders caused by absence of paternal or maternal contributions of the chromosome region 15q11-q13, resulting from deletions, uniparental disomy (UPD), or rare imprinting mutations. Molecular cytogenetic diagnosis is currently performed using a combination of fluorescence in situ hybridisation (FISH), DNA polymorphism analysis, and DNA methylation analysis. Only methylation analysis will detect all three categories of PWS abnormalities, but its reliability in tissues other than peripheral blood has not been examined extensively. Therefore, we examined the methylation status at the CpG island of the small nuclear ribonucleoprotein associated polypeptide N (SNRPN) gene and at the PW71 locus using normal and abnormal lymphoblast (LE) cell lines (n=48), amniotic fluid (AF) cell cultures (n=25), cultured chorionic villus samples (CVS, n=17), and fetal tissues (n=18) by Southern blot analysis with methylation sensitive enzymes. Of these samples, 20 LB cell lines, three AF cultures, one CVS, and 15 fetal tissues had been previously diagnosed as having deletions or UPD by other molecular methods. Methylation status at SNRPN showed consistent results when compared with FISH or DNA polymorphism analysis using all cell types tested. However, the methylation pattern for PW71 was inconsistent when compared with other tests and should therefore not be used on tissues other than peripheral blood. We conclude that SNRPN, but not PW71, methylation analysis may be useful for diagnosis of PWS/AS on LB cell lines, cultured amniotic fluid, or chorionic villus samples and will allow, for the first time, prenatal diagnosis for families known to carry imprinting centre defects. C1 UNIV CHICAGO,CTR MED GENET,CHICAGO,IL 60637. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. CHILDRENS HOSP EASTERN ONTARIO,OTTAWA,ON,CANADA. SINAI HOSP,BALTIMORE,MD. NR 16 TC 31 Z9 32 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 1996 VL 33 IS 12 BP 1011 EP 1014 DI 10.1136/jmg.33.12.1011 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WA281 UT WOS:A1996WA28100008 PM 9004133 ER PT J AU Cohen, JI Moskal, T Shapiro, M Purcell, RH AF Cohen, JI Moskal, T Shapiro, M Purcell, RH TI Varicella in chimpanzees SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE varicella-zoster virus; herpes zoster; chicken pox ID ZOSTER VIRUS; GUINEA-PIGS; INFECTION; VACCINE AB Two chimpanzees were inoculated subcutaneously with the wild-type Oka strain of varicella-zoster virus (VZV). Viral DNA was detected in peripheral brood mononuclear cells of both animals using the polymerase chain reaction (PCR) shortly after inoculation. Ten days after inoculation both animals developed an erythematous, papular rash near the site of inoculation that extended into the adjacent dermatome. Viral DNA was found by PCR in a skin biopsy from one of the animals at the time of the rash. While only two animals were studied, the development of a mild form of varicella in chimpanzees indicates that these animals might be useful for molecular studies of viral genes involved in virulence or attenuation of VZV. (C) 1996 Wiley-Liss, Inc. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,BETHESDA,MD 20892. BIOQUAL INC,ROCKVILLE,MD. RP Cohen, JI (reprint author), NIAID,CLIN INVEST LAB,MOL VIROL UNIT,NIH,BLDG 10,RM 11N214,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI-05069] NR 18 TC 18 Z9 19 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 1996 VL 50 IS 4 BP 289 EP 292 DI 10.1002/(SICI)1096-9071(199612)50:4<289::AID-JMV2>3.0.CO;2-4 PG 4 WC Virology SC Virology GA VV624 UT WOS:A1996VV62400002 PM 8950684 ER PT J AU Jahnke, GD Trempus, CS Kari, FW DiAugustine, RP AF Jahnke, GD Trempus, CS Kari, FW DiAugustine, RP TI Expression of a prolactin-like factor in preneoplastic and neoplastic mouse mammary gland and cells SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID EPITHELIAL-CELLS; MESSENGER-RNA; MORPHOGENESIS INVIVO; MURINE LYMPHOCYTES; RECEPTOR; LINE; GENE; IDENTIFICATION; INVITRO; TISSUES AB Prolactin is a member of the growth hormone family and is required for the growth and terminal differentiation of the mammary gland. Ectopic production of this hormone has been reported in including rat, sheep, goat and mammary tissues. In this study, mouse mammary cell lines, xenographs in the mammary gland from these cell lines and from hyperplastic alveolar nodules, spontaneous tumors, and normal tissues were studied for de novo production of this growth factor. Prolactin transcripts were found by reverse transcriptase PCR in some neoplastic and preneoplastic tissues and in mouse mammary cell lines, NOG8 and CDNR4, but were not detected in the normal mouse mammary gland. Northern analysis revealed a 1 kb transcript for both cell lines that co-migrated with the prolactin pituitary transcript. Conditioned medium from NOG8 cells was positive for prolactin bioactivity by the Nb2 rat lymphoma cell proliferation assay, and Western analysis revealed the presence of immunoreactive proteins at M(r) 14 000 and 60 000. Prolactin-like bioactivity was not detected in conditioned medium from CDNR4 cells, but an immunoreactive protein of M(r) 60 000 was detected by Western analysis. The mouse mammary cell line, Comma D, was negative for prolactin transcripts; however, adenocarcinomas derived from inoculation of Comma D cells into the cleared mammary fat pad were positive by reverse transcriptase PCR in two of four cases. Hyperplastic outgrowths maintained in the cleared mammary fat pad as well as spontaneous tumors were positive for prolactin transcripts in one of four cases. These results suggest that prolactin can be produced ectopically by the neoplastic mouse mammary gland. RP Jahnke, GD (reprint author), NIEHS,HORMONES & CANC SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 2 Z9 2 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 1996 VL 17 IS 3 BP 247 EP 256 DI 10.1677/jme.0.0170247 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ711 UT WOS:A1996VZ71100008 PM 8981231 ER PT J AU Gozes, I Brenneman, DE AF Gozes, I Brenneman, DE TI Activity-dependent neurotrophic factor (ADNF) - An extracellular neuroprotective chaperonin SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Review DE VIP; hsp60; stress proteins; astroglia; growth factors ID VASOACTIVE-INTESTINAL-PEPTIDE; HEAT-SHOCK PROTEIN; SPINAL-CORD CULTURES; RAT SUPRACHIASMATIC NUCLEUS; INFLUENCE NEURONAL SURVIVAL; LEUKEMIA INHIBITORY FACTOR; NEUROKININ SUBSTANCE-P; MESSENGER-RNA; GENE-EXPRESSION; ELECTRICAL-ACTIVITY AB To understand and intervene in neuronal cell death, intensive investigations have been directed at the discovery of intracellular and extracellular factors that provide natural neuroprotection. This goal has fundamental importance for both rational strategies for the treatment of neurodegenerative diseases and also the delineation of molecular mechanisms that regulate nervous system differentiation and growth. We have discovered a potential interface among these fields of research with activity-dependent neurotrophic factor (ADNF), a protein containing sequence homologies to intracellular stress proteins that is found in the extracellular milieu of astroglial cells incubated with the neuropeptide vasoactive intestinal peptide (VIP). Femtomolar concentrations of ADNF and a short peptide sequence derived from it (a peptidergic active site) protected neurons from death associated with a broad range of toxins, including those related to Alzheimer's disease, the human immunodeficiency virus, excitotoxicity, and electrical blockade. Because the activity of the protein was mimicked by a short peptide fragment, this peptide is now proposed as a lead compound for drug development against neurodegeneration. C1 NICHHD,NIH,DEV NEUROBIOL LAB,SECT DEV & MOL PHARMACOL,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 81 TC 57 Z9 59 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD WIN PY 1996 VL 7 IS 4 BP 235 EP 244 DI 10.1007/BF02737061 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VX643 UT WOS:A1996VX64300001 PM 8968945 ER PT J AU Jain, P Garraffo, HM Yeh, HJC Spande, TF Daly, JW Andriamaharavo, NR Andriantsiferana, M AF Jain, P Garraffo, HM Yeh, HJC Spande, TF Daly, JW Andriamaharavo, NR Andriantsiferana, M TI A 1,4-disubstituted quinolizidine from a Madagascan mantelline frog (Mantella) SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DIELS-ALDER REACTION; POISON-FROG; ALKALOIDS; DENDROBATIDAE; PUMILIOTOXINS; INDOLIZIDINES; HISTRIONICOTOXINS; PYRROLIZIDINES; GEPHYROTOXINS; 205A AB A major alkaloid, 217A, in skin extracts of a mantelline frog (Mantella baroni) was isolated by HPLC and the structure defined by H-1-NMR spectral analysis as (1R,4S,10S)- or (1R,4R,10R)-1-methyl-4-(Z)-(1-pent-2-en-4-ynyl) quinolizidine ii). Four other alkaloids-207I (2), 231A (3), 233A (4), and 235E' (5)-detected in frog skin extracts are proposed to be 1,4-disubstituted quinolizidines based on diagnostic mass and FTIR spectra. C1 NIDDKD, BIOORGAN CHEM LAB, NIH, BETHESDA, MD 20892 USA. UNIV ANTANANARIVO, LAB CHIM ORGAN PROD NAT, ANTANANARIVO 1001, MALAGASY REPUBL. NR 18 TC 23 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 1996 VL 59 IS 12 BP 1174 EP 1178 DI 10.1021/np9605100 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA WA559 UT WOS:A1996WA55900018 PM 8988603 ER PT J AU Mauger, AB AF Mauger, AB TI Naturally occurring proline analogues SO JOURNAL OF NATURAL PRODUCTS LA English DT Review ID ANTITUMOR CYCLIC PENTAPEPTIDES; MYCOPLANECINUS SUBSP-NOV; BULGE-INDUCING ACTIVITY; ASTER-TATARICUS; ZALERION-ARBORICOLA; AMINO-ACIDS; STRUCTURE ELUCIDATION; PEPTIDE ALKALOIDS; LEUCINOSTATIN-A; KAINIC ACID RP Mauger, AB (reprint author), NCI,DEV THERAPEUT PROGRAM,DRUG SYNTH & CHEM BRANCH,BETHESDA,MD 20892, USA. NR 195 TC 75 Z9 75 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 DEC PY 1996 VL 59 IS 12 BP 1205 EP 1211 DI 10.1021/np9603479 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA WA559 UT WOS:A1996WA55900027 PM 8988607 ER PT J AU MacArthur, L AF MacArthur, L TI AP-1-Related proteins bind to the enkephalin CRE-2 element in adrenal chromaffin cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE enkephalin; transcription; neuropeptide; chromaffin cells; adrenal gland; AP-1 transcription factor ID CAMP-RESPONSE-ELEMENT; A GENE-EXPRESSION; CYCLIC-AMP; PROENKEPHALIN GENE; MESSENGER-RNA; GROWTH-FACTOR; TRANSCRIPTION; ENHANCER; BIOSYNTHESIS; MEDULLA AB Chromaffin cells of the adrenal medulla are neural crest-derived neuroendocrine cells that express neuropeptide genes in vivo and in vitro. As such these cells are useful for examining tissue- and cell-specific regulation of the enkephalin gene. We previously demonstrated that the chromatin configuration of the enkephalin gene correlated with its tissue-specific expression in the adrenal medulla and primary chromaffin cell cultures. In this study we examine and characterize binding of transcription factors to the enkephalin promoter/enhancer region. Gel shift analyses of this region with extracts from chromaffin cells and PC12 cells (a pheochromocytoma cell line that does not express the enkephalin gene) demonstrate that all detectable binding is to ENKCRE-2, a cyclic AMP response-like element, and that the binding is cell specific. Gel shift and supershift analyses show that, unlike reports demonstrating that binding activity in the CNS is composed of the cyclic AMP response element binding protein, CREB, the majority of protein binding in chromaffin cells is from the AP-I family of transcription factors. This binding is composed of c-Jun, JunD, and possibly a novel Fos-related protein(s). These data suggest enkephalin gene expression in the adrenal gland is controlled by cell-specific binding of transcription factors from the Fos/Jun families to the enkephalin CRE-2 element, Furthermore, these data suggest at least two different modes of enkephalin gene regulation exist between endocrine and neuronal tissues. RP MacArthur, L (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,CELLULAR & MOL MECHANISMS SECT,BLDG 49,ROOM 1A-11,BETHESDA,MD 20892, USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1996 VL 67 IS 6 BP 2256 EP 2264 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VU244 UT WOS:A1996VU24400004 PM 8931456 ER PT J AU Pascale, A Fortino, I Govoni, S Trabucchi, M Wetsel, WC Battaini, F AF Pascale, A Fortino, I Govoni, S Trabucchi, M Wetsel, WC Battaini, F TI Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE aging; rat brain cortex; RACK1 protein; protein kinase C activity; protein kinase C isoforms ID PHOSPHOINOSITIDE METABOLISM; INTRACELLULAR RECEPTORS; BINDING-PROTEINS; NERVOUS-SYSTEM; IN-VIVO; IDENTIFICATION; TRANSLOCATION; CALCIUM; RELEASE; CELLS AB Several laboratories have reported a lack of protein kinase C (PKC) activation in response to various stimuli in the brain of aged rats. It has been suggested that changes in lipid membrane composition could be related to this functional deficit. However, recent evidence has indicated that the translocation of PKC to the different subcellular compartments is controlled by protein-protein interactions. Recently, a class of proteins, termed receptors for activated C kinase (RACKs), have been described that bind PKC. The present study was conducted to determine whether alterations in RACK1, the best-characterized member of RACKs, were associated with changes in translocation and expression of PKC. Quantitative immunoblotting revealed that RACK1 content was decreased by similar to 50% in aged rat brain cortex, compared with that in adult and middle-aged animals. The levels of calcium-independent PKC delta and epsilon, interacting with RACK1, and related calcium-independent PKC activity were not modified by the aging process. By comparison, phorbol ester-stimulated translocation of this activity and of PKC delta and epsilon immunoreactivity was absent in cortex from aged animals, as well as the translocation of the calcium-dependent PKC beta, also known to interact with RACK1. These results indicate that a deficit in RACK1 may contribute to the functional impairment in PKC activation observed in aged rat brain. C1 UNIV MILAN,INST PHARMACOL SCI,I-20133 MILAN,ITALY. UNIV PAVIA,INST PHARMACOL,I-27100 PAVIA,ITALY. UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,ROME,ITALY. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015 OI Govoni, Stefano/0000-0002-7243-6837 NR 34 TC 68 Z9 69 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1996 VL 67 IS 6 BP 2471 EP 2477 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VU244 UT WOS:A1996VU24400028 PM 8931480 ER PT J AU Calhoun, ME Jucker, M Martin, LJ Thinakaran, G Price, DL Mouton, PR AF Calhoun, ME Jucker, M Martin, LJ Thinakaran, G Price, DL Mouton, PR TI Comparative evaluation of synaptophysin-based methods for quantification of synapses SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; SYNAPTIC VESICLE; CEREBRAL-CORTEX; TEMPORAL-LOBE; RAT; HIPPOCAMPUS; EXPRESSION; NEURONS; PATHOLOGY; DEMENTIA AB Development, ageing, and a variety of neurological disorders are characterized by selective alterations in specific populations of nerve cells which are, in turn, associated with changes in the numbers of synapses in the target fields of these neurons. To begin to delineate the significance of changes in synapses in development, ageing, and disease, it is first essential to quantify the number of synapses in defined regions of the CNS. In the past, investigators have used EM methods to assess synapse numbers or density, but these approaches are costly, labour intensive, and technically difficult, particularly in autopsy material. To begin to define reliable strategies useful for studies of both animals and humans, we used three techniques to measure synaptophysin immunoreactivity in rat brain. The levels of synaptophysin protein were determined by Western blots of five hippocampal subregions; the intensity of synaptophysin-immunoreactivity in dentate gyrus and stratum oriens was determined by optical densitometry of immunocytochemically stained sections; and the total number of synaytophysin-immunoreactivity presynaptic boutons in dentate gyrus and stratum oriens was assessed by unbiased stereology. Each approach has advantages and disadvantages. Western blotting is the least time-consuming of the three methods and allows simultaneous processing of multiple samples. In systematically sampled histological sections, both densitometry and stereology allow precise definition of the region of interest, and the stereological optical disector method allows quantitation of the numbers of synaptophysin-immunoreactive boutons. Stereology was the only method that clearly demonstrated greater synaptophysin-immunoreactivity in the dentate gyrus as compared to stratum oriens. The use of systematic sampling and the disector technique offer a high degree of anatomical resolution (lacking in Western blot methods) and has quantitative advantage over the greyscale-based density approach. Thus, at present, stereology is the most useful method for estimating synaptic numbers in defined regions of the brain. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. FU NIA NIH HHS [AG 05146]; NINDS NIH HHS [NS 10580, NS 20471] NR 33 TC 160 Z9 173 U1 4 U2 15 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD DEC PY 1996 VL 25 IS 12 BP 821 EP 828 DI 10.1007/BF02284844 PG 8 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA WD450 UT WOS:A1996WD45000013 PM 9023727 ER PT J AU Koehler, NKU Martin, R Wietholter, H AF Koehler, NKU Martin, R Wietholter, H TI The antibody repertoire in experimental allergic neuritis: Evidence for PMP-22 as a novel neuritogen SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE experimental allergic neuritis; complete Freund's adjuvant; Semiquantitative Western blotting; PNS myelin; HNK-1; PMP-22 ID GUILLAIN-BARRE-SYNDROME; MYELIN-ASSOCIATED GLYCOPROTEIN; PERIPHERAL-NERVE MYELIN; T-CELL LINES; LIPID HAPTENS; LEWIS RAT; DEMYELINATION; PROTEIN; IDENTIFICATION; NEUROPATHY AB Experimental allergic neuritis (EAN) is an autoimmune disease that serves as an animal model for the Guillain-Barre syndrome (GBS). in both disorders there is still great uncertainty as to the significance and diversity of autoantibodies involved. We focused on the characterization of serum antibody production in response to various peripheral nervous system (PNS) myelin proteins during the course of actively induced EAN in Lewis rats. These data were compared with EAN induced by adoptive transfer of P2-specific CD4(+) T cells (AT-EAN) and with inoculation with complete Freund's adjuvant (CFA) alone. Semiquantitative Western blotting was applied to measure serum IgM and IgG titers against specific myelin proteins, including P2, P0, myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and PMP-22. Considerable differences in the dynamics of antibody titers against individual myelin proteins were observed in active EAN and after inoculation with CFA alone. Our data suggest a pathogenic role of IgM antibodies against HNK adhesion carbohydrate epitope expressing PNS proteins P0, MAG and PMP-22. Among these, PMP-22, a novel candidate neuritogen may be of particular relevance. Thus, we provide evidence for the involvement of antibody-mediated immune responses in actively induced EAN and a basis for similar studies on related human disorders such as GBS or other demyelinating neuropathies. C1 UNIV TUBINGEN,DEPT NEUROL,D-72076 TUBINGEN,GERMANY. NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. BURGER HOSP,DEPT NEUROL,D-70191 STUTTGART,GERMANY. RP Koehler, NKU (reprint author), UNIV CALIF SAN FRANCISCO,DEPT NEUROL,513 PARNASSUS AVE,SAN FRANCISCO,CA 94143, USA. NR 50 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 1996 VL 71 IS 1-2 BP 179 EP 189 DI 10.1016/S0165-5728(96)00141-5 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VZ443 UT WOS:A1996VZ44300024 PM 8982118 ER PT J AU Basta, M Illa, I Dalakas, MC AF Basta, M Illa, I Dalakas, MC TI Increased in vitro uptake of the complement C3b in the serum of patients with Guillain-Barre syndrome, myasthenia gravis and dermatomyositis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE complement; quantitative assay; neuromuscular disorders ID INTRAVENOUS IMMUNE GLOBULIN; IMMUNOGLOBULIN; FRAGMENTS; TRIAL AB To examine the role of complement in certain autoimmune neuromuscular diseases, we used an in-vitro quantitative complement uptake assay that allows measurement of the capacity of patients' sera to deposit fragments of the third complement component onto sensitized targets. C3 uptake was significantly higher in patients with active dermatomyositis, Guillain-Barre syndrome and myasthenia gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake assay supports the role of C3b neoantigen and Membranolytic Attack Complex deposition in the target tissues and may be a useful tool to monitor disease activity Inpatients with complement-mediated neurological disorders. RP Basta, M (reprint author), NINCDS,NEUROMUSCULAR DIS SECT,NIH,BLDG 10,RM 4N248,BETHESDA,MD 20892, USA. OI Basta, Milan/0000-0001-5958-9241 NR 16 TC 20 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 1996 VL 71 IS 1-2 BP 227 EP 229 DI 10.1016/S0165-5728(96)00133-6 PG 3 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VZ443 UT WOS:A1996VZ44300030 PM 8982124 ER PT J AU Higgins, JJ HarveyWhite, JD Nee, LE Colli, MJ Grossi, TA Kopin, IJ AF Higgins, JJ HarveyWhite, JD Nee, LE Colli, MJ Grossi, TA Kopin, IJ TI Brain MRI, lumbar CSF monoamine concentrations, and clinical descriptors of patients with spinocerebellar ataxia mutations SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE spinocerebellar degeneration; cerebellar ataxia; biogenic monoamines; nuclear magnetic resonance ID INHERITED OLIVOPONTOCEREBELLAR ATROPHY; DOMINANT CEREBELLAR-ATAXIA; MACHADO-JOSEPH DISEASE; DEGENERATION; FAMILY; MAPS; FEATURES; TYPE-1; UNIQUE; SYSTEM AB Objectives-To serially assess changes in lumbar CSF biogenic amines, radiographic characteristics, and neurological signs in 34 patients with dominantly inherited ataxia. Methods-Mutational analysis was used to identify genetic subgroups. Annual assessment of lumbar CSF monoamine metabolites using a gas chromatographic/mass spectrometric method and morphometric measurements of the cerebellum, pens, and the cervical spinal cord on MRI were analysed for each patient and compared with normal controls. Results-Patients with CAG trinucleotide repeat expansions on chromosome 6p (mutSCA1) and chromosome 14q (mutSCA3) had only about one half the normal concentrations of lumbar CSF homovanillic acid (HVA) whereas, 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similar to those in age matched normal subjects. The HVA and 5-HIAA concentrations in clinically similar patients without mutSCA1 or mutSCA3 were normal. One year after the first study, HVA concentrations were reduced by a mean of 22% regardless of the patient's SCA mutation. Abnormalities on MRT were consistent with a spinopontine atrophy in patients with mutSCA3, spinopontocerebellar atrophy in patients with mutSCA1, and ''pure'' cerebellar atrophy in patients without these mutations. Conclusions-Quantitative MRT measurements were not useful in monitoring progression of disease but lumbar CSF HVA concentrations and total scores on a revised version of the ataxia clinical rating scale seemed to progress in parallel. C1 NINCDS,AMINERG MECH SECT,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Higgins, JJ (reprint author), NINCDS,CLIN NEUROGENET UNIT,MED NEUROL BRANCH,NIH,BLDG 36,RM 5N234,BETHESDA,MD 20892, USA. NR 33 TC 7 Z9 7 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD DEC PY 1996 VL 61 IS 6 BP 591 EP 595 DI 10.1136/jnnp.61.6.591 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA VY193 UT WOS:A1996VY19300009 PM 8971105 ER PT J AU Schneider, C Gold, R Dalakas, MC Schmied, M Lassmann, H Toyka, KV Hartung, HP AF Schneider, C Gold, R Dalakas, MC Schmied, M Lassmann, H Toyka, KV Hartung, HP TI MHC class I-mediated cytotoxicity does not induce apoptosis in muscle fibers nor in inflammatory T cells: Studies in patients with polymyositis, dermatomyositis, and inclusion body myositis SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE autoimmune disorders; Fas antigen; human inflammatory myopathies; MHC class I cytotoxicity; T cell apoptosis ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GUILLAIN-BARRE-SYNDROME; MULTIPLE-SCLEROSIS; RECEPTOR REPERTOIRE; NERVOUS-SYSTEM; LYMPHOCYTES; DEATH; ANTIGEN; IMMUNOPATHOGENESIS; MYOPATHIES AB Apoptosis plays a crucial role in natural recovery from T cell-mediated autoimmune disorders of the nervous system. Whether apoptosis also occurs in human inflammatory myopathies is unclear. In this study we examined muscle biopsy specimens from untreated patients with polymyositis (n = 12), dermatomyositis (n = 12), and inclusion body myositis (n = 12) for the presence of apoptosis using morphological criteria and DNA fragmentation by in situ tailing. In all these disorders, only rare T cells exhibited signs of apoptosis by nuclear morphology and in situ labeling techniques. Although Fas-expression was upregulated in a few inflammatory cells, increased apoptosis of the surrounding T cells was not observed. Further, nuclei of degenerating muscle fibers did not show morphological signs of apoptosis and were not labeled by the tailing reaction. We conclude that in the inflammatory myopathies, T cell inflammation is not cleared by apoptosis and affected muscle fibers do not die by apoptosis. The observations are consistent with the non-self-limited nature of these disorders and suggest that, in contrast to the nervous system, the local microenvironment in muscle does not deliver pro-apoptotic stimuli. C1 UNIV WURZBURG,DEPT NEUROL,CLIN RES UNIT MULTIPLE SCLEROSIS,D-8700 WURZBURG,GERMANY. NINCDS,NIH,BETHESDA,MD. AUSTRIAN ACAD SCI,EXPT NEUROPATHOL RES UNIT,A-1010 VIENNA,AUSTRIA. NR 28 TC 71 Z9 72 U1 0 U2 0 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 DEC PY 1996 VL 55 IS 12 BP 1205 EP 1209 DI 10.1097/00005072-199612000-00003 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VW890 UT WOS:A1996VW89000004 PM 8957443 ER PT J AU Krauzlis, RJ Miles, FA AF Krauzlis, RJ Miles, FA TI Initiation of saccades during fixation or pursuit: Evidence in humans for a single mechanism SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SHORT REACTION-TIMES; EYE-MOVEMENTS; SMOOTH-PURSUIT; EXPRESS-SACCADES; MONKEY; ATTENTION; NEURONS; TARGET; FIELD AB 1. In four human subjects, we measured the latency of saccadic eye movements made to a second, eccentric target after an initial, foveated target was extinguished. In separate interleaved trials, the targets were either both stationary (''fixation'') or both moving with the same velocity (''pursuit''). For both fixation and pursuit trials, we extinguished the first target at randomized times during maintained fixation or pursuit and varied the time interval (''gap duration'') before the appearance of the second target. 2. During both fixation and pursuit, the presence of a 200-ms gap reduced the latencies of saccades, compared with those obtained with no gap. For two subjects, we imposed additional, intermediate gap durations and found that saccade latencies varied as a function of gap duration. Furthermore, the latencies of saccades elicited during pursuit displayed the same dependence on gap duration as those elicited during fixation. 3. Our results demonstrate that the ''gap effect'' observed for saccades made during fixation also occurs for saccades made during pursuit. To the extent that the gap effect on saccade latency reflects a mechanism underlying the release of fixation, our results suggest that the same mechanism is invoked for saccades made during pursuit. From the viewpoint of initiating saccades, the existence of separate fixation and pursuit systems may be irrelevant. RP Krauzlis, RJ (reprint author), NEI,SENSORIMOTOR RES LAB,NIH,BLDG 49,RM 2A-50,BETHESDA,MD 20892, USA. NR 25 TC 34 Z9 34 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1996 VL 76 IS 6 BP 4175 EP 4179 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WA803 UT WOS:A1996WA80300052 PM 8985910 ER PT J AU Lalonde, FM Martin, A Myslobodsky, MS AF Lalonde, FM Martin, A Myslobodsky, MS TI Increased prevalence of septal cavitation in a nonschizophrenic sample: An MRI study of HIV-infected individuals SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SCHIZOPHRENIC-PATIENTS; ABNORMALITIES; PELLUCIDUM; AIDS; PERFORMANCE; DEMENTIA; HEADACHE; ATROPHY; SCANS AB Analyses of MRI scans of 26 asymptomatic HIV-infected individuals (HIV+) and 10 HIV-seronegative psychiatric control subjects (HIV-) revealed an incidental finding: 50% of the HIV+ subjects had a discernible cleft in the septum pellucidum (cavum septi pellucidi; CSP), compared to only 20% of the HIV- control subjects. HIV+ subjects with CSP were more likely to complain of sensory changes and performed more poorly on specific neuropsychological tests when compared with HIV+ subjects without CSP. These findings suggest that elevated rates of CSP are not limited to the schizophrenic population. CSP may be a marker of premorbid events that increase the vulnerability to cognitive and perhaps behavioral sequelae of neurologic disease or injury. C1 TEL AVIV UNIV,PSYCHOBIOL RES UNIT,RAMAT AVIV,ISRAEL. RP Lalonde, FM (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,BETHESDA,MD 20892, USA. RI martin, alex/B-6176-2009 NR 32 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1996 VL 8 IS 1 BP 47 EP 53 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TR911 UT WOS:A1996TR91100007 PM 8845701 ER PT J AU Tella, SR Ladenheim, B Andrews, AM Goldberg, SR Cadet, JL AF Tella, SR Ladenheim, B Andrews, AM Goldberg, SR Cadet, JL TI Differential reinforcing effects of cocaine and GBR-12909: Biochemical evidence for divergent neuroadaptive changes in the mesolimbic dopaminergic system SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; GBR-12909; self-administration; reinforcing effects; neuroadaptation; dopamine receptors; dopamine transporters; dopamine; drug addiction; drug withdrawal ID RAT NUCLEUS-ACCUMBENS; BIOGENIC-AMINE TRANSPORTERS; H-3 MAZINDOL BINDING; BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; NEUROCHEMICAL CHANGES; WITHDRAWAL; DRUG; SITES; INJECTIONS AB The dopamine (DA) transporter is thought to be the primary mediator of reinforcing effects of cocaine. In the present study, an intravenous drug self-administration procedure, in vitro autoradiography, and HPLC methods were used to investigate possible differences in reinforcing and neuroadaptive responses to cocaine versus GBR-12909, a selective inhibitor of the DA transporter with a postulated therapeutic use in cocaine abuse. Drug-naive rats readily acquired and subsequently maintained cocaine self-administration behavior during 2 hr daily sessions over a prolonged period. In contrast, although GBR-12909 was initially self-administered, both cocaine-naive and cocaine-trained rats failed to maintain self-administration behavior to GBR-12909 over prolonged periods of time. After self-administration responding decreased with GBR-12909, rats showed a delay of 6.6 = 1.3 sessions in reacquiring consistent cocaine self-administration. Moreover, when GBR-12909 was again substituted for cocaine, they failed to self-administer GBR-12909, even during the initial days of testing. In contrast, after extinction of self-administration responding by water substitution, rats readily selfadministered both cocaine and GBR-12909. Cocaine self-administration upregulated DA transporters, whereas water-substituted cocaine withdrawal upregulated both DA transporters and D1 receptors. Unlike cocaine. GBR-12909 self-administration by itself altered neither DA transporters nor. D1 or D2 receptors. Nevertheless, substitution of GBR-12909 for cocaine reversed the cocaine-induced upregulation of DA transporters and reduced DA and dihydroxyphenylacetic acid levels in the mesolimbic system. These data suggest that cocaine and GBR-12909 differentially affect dopaminergic systems and also cause different reinforcing and neuroadaptive effects. GBR-12909-like compounds may be useful pharmacotherapeutic agents for cocaine addiction. Upregulation of DA transporters and D1 receptors might play important roles in the neuroadaptive cascade that leads to cocaine addiction and withdrawal. C1 NIDA,MOL NEUROPSYCHIAT SECT,NIH,BALTIMORE,MD 21224. NIDA,BEHAV PHARMACOL & GENET SECT,NIH,BALTIMORE,MD 21224. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Tella, SR (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 FU NIDA NIH HHS [DA08830] NR 68 TC 75 Z9 75 U1 3 U2 3 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 DEC 1 PY 1996 VL 16 IS 23 BP 7416 EP 7427 PG 12 WC Neurosciences SC Neurosciences & Neurology GA VY433 UT WOS:A1996VY43300002 PM 8922397 ER PT J AU Movshon, JA Newsome, WT AF Movshon, JA Newsome, WT TI Visual response properties of striate cortical neurons projecting to area MT in macaque monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE visual cortex; motion processing; visual receptive fields; cortico-cortical projections; antidromic activation; direction selectivity ID RECEPTIVE-FIELD PROPERTIES; SUPERIOR TEMPORAL SULCUS; COMPLEX CELLS; TOPOGRAPHIC ORGANIZATION; LAMINAR DISTRIBUTION; AFFERENT BASIS; CORTEX; CONNECTIONS; MOTION; CAT AB We have previously shown that some neurons in extrastriate area MT are capable of signaling the global motion of complex patterns; neurons randomly sampled from V1, on the other hand, respond only to the motion of individual oriented components. Because only a small fraction of V1 neurons projects to MT, we wished to establish the processing hierarchy more precisely by studying the properties of those neurons projecting to MT, identified by antidromic responses to electrical stimulation of MT. The neurons that project from V1 to MT were directionally selective and, like other V1 neurons, responded only to the motion of the components of complex patterns. The projection neurons were predominantly ''special complex,'' responsive to a broad range of spatial and temporal frequencies, and sensitive to very low stimulus contrasts. The projection neurons thus comprise a homogeneous and highly specialized subset of V1 neurons, consistent with the notion that V1 acts as clearing house of basic visual measurements, distributing information appropriately to higher cortical areas for specialized analysis. C1 NYU,HOWARD HUGHES MED INST,NEW YORK,NY 10003. STANFORD UNIV,SCH MED,DEPT NEUROBIOL,STANFORD,CA 94305. NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. RP Movshon, JA (reprint author), NYU,CTR NEURAL SCI,4 WASHINGTON PL,ROOM 809,NEW YORK,NY 10003, USA. FU NEI NIH HHS [EY 02017] NR 49 TC 364 Z9 364 U1 2 U2 11 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 DEC 1 PY 1996 VL 16 IS 23 BP 7733 EP 7741 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VY433 UT WOS:A1996VY43300034 PM 8922429 ER PT J AU Schweitzer, ES Jeng, CJ TaoCheng, JH AF Schweitzer, ES Jeng, CJ TaoCheng, JH TI Selective localization and regulated release of calcitonin gene-related peptide from dense-core vesicles in engineered PC12 cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE LDCV; sorting; packaging; trophic factors; neuropeptide ID NERVE GROWTH-FACTOR; SYNAPTIC-LIKE MICROVESICLES; TRANS-GOLGI NETWORK; NEUROMUSCULAR-JUNCTION; SECRETORY PATHWAY; PHEOCHROMOCYTOMA CELLS; SPINAL-CORD; ACETYLCHOLINE-RECEPTOR; CHROMAFFIN GRANULES; TARGETING SIGNAL AB Introduction of the gene for calcitonin into the neuroendocrine PC12 cell line resulted in the expression of the neuronal-specific splice product, calcitonin gene-related peptide (CGRP), Expression of this neuropeptide did not require treatment of the PC12 cells with NGF, By all available criteria, including biochemical, immunological, and morphological analysis, we have determined that the CGRP in stably transfected PC12 cells is sorted selectively into the large, dense-core catecholamine-containing secretory vesicles, Conversely, the CORP is excluded from the small, synaptophysin-rich vesicles present in the same cells, Stimulation conditions that trigger the release of catecholamines cause a parallel burst in the release of CGRP, In all these respects, the engineered PC12 cells process the foreign CGRP in a manner similar to that seen in spinal motor neurons in vivo, These results indicate that this small (37 amino acids) peptide contains sorting information sufficient for targeting to large, dense-core vesicles in heterologous cells, placing very narrow constraints on the possible location of sorting signals, In addition, this CGRP-expressing cell line opens the possibility of studying the physiological role of CGRP in the establishment and maintenance of neuromuscular contacts. (C) 1996 Wiley-Liss, Inc. C1 NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. RP Schweitzer, ES (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROBIOL,10833 LE CONTE AVE,LOS ANGELES,CA 90029, USA. FU NINDS NIH HHS [R01 NS23084] NR 64 TC 5 Z9 5 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 DEC 1 PY 1996 VL 46 IS 5 BP 519 EP 530 PG 12 WC Neurosciences SC Neurosciences & Neurology GA VW044 UT WOS:A1996VW04400001 PM 8951664 ER PT J AU Zunkeler, B Carson, RE Olson, J Blasberg, RG DeVroom, H Lutz, RJ Saris, SC Wright, DC Kammerer, W Patronas, NJ Dedrick, RL Herscovitch, P Oldfield, EH AF Zunkeler, B Carson, RE Olson, J Blasberg, RG DeVroom, H Lutz, RJ Saris, SC Wright, DC Kammerer, W Patronas, NJ Dedrick, RL Herscovitch, P Oldfield, EH TI Quantification and pharmacokinetics of blood-brain barrier disruption in humans SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain neoplasm; glioma; blood-brain barrier; clinical trial; blood-brain barrier disruption; pharmacokinetics; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; TO-TUMOR TRANSPORT; METHOTREXATE DELIVERY; ARTERY INFUSIONS; CAROTID-ARTERY; DRUG INFUSION; CHEMOTHERAPY; RB-82; PERMEABILITY; RUBIDIUM-82 AB Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K-1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K-1 in all patients. Baseline K-1 values were 2.1 +/- 1.4 and 34.1 +/- 22.1 mu l/minute/ml (+/- standard deviation) for brain and tumor, respectively. The peak absolute increases in K-1 following HBBBD were 20.8 +/- 11.7 and 19.7 +/- 10.7 mu l/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K-1 to near baseline for brain and tumor were 8.1 +/- 3.8 and 4.2 +/- 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure tome at concentrations above 1 mu M, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-train barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs. C1 NINCDS, SURG NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, POSITRON EMISS TOMOG DEPT, BETHESDA, MD 20892 USA. NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 48 TC 66 Z9 69 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 1996 VL 85 IS 6 BP 1056 EP 1065 DI 10.3171/jns.1996.85.6.1056 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VU233 UT WOS:A1996VU23300010 PM 8929495 ER PT J AU Lane, JH Sasseville, VG Smith, MO Vogel, P Pauley, DR Heyes, MP Lackner, AA AF Lane, JH Sasseville, VG Smith, MO Vogel, P Pauley, DR Heyes, MP Lackner, AA TI Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE neuroAIDS; leukocyte traffick; quinolinic acid; image analysis ID CENTRAL-NERVOUS-SYSTEM; NONPATHOGENIC MOLECULAR CLONES; CELL-ADHESION MOLECULE-1; RHESUS MACAQUES; CEREBROSPINAL-FLUID; QUINOLINIC ACID; RESIDENT MICROGLIA; AIDS ENCEPHALITIS; INFECTION; BRAIN AB During peak viremia and initial antibody response, rhesus macaques infected with pathogenic and nonpathogenic isolates of SIV show distinct differences in viral load and tissue distribution. Animals infected with pathogenic isolates of SIV invariably have virus in the CSF and brain parenchyma by two weeks postinoculation, whereas animals infected with nonpathogenic isolates do not. Mechanisms underlying neuroinvasion by SIV and HIV are unknown, but recruitment of latently infected mononuclear cells from the peripheral circulation (Trojan horse theory) is frequently proposed, Circulating monocytes, from which perivascular macrophage/microglia are derived, are a likely vehicle for cell-associated transport of virus across the blood-brain barrier. This transport and the kinetics of perivascular macrophage/microglial turnover in the CNS likely depend on endothelial and leukocyte adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), which has previously been shown to be upregulated on cerebrovascular endothelium in SIV encephalitis. To investigate the role of peripheral monocyte recruitment into the perivascular macrophage/microglial cell pool at the time of initial viral neuroinvasion, we examined the temporal relationships among perivascular macrophage/microglia density, endothelial VCAM-1 expression and localization of viral nucleic acid in the CNS of macaques acutely infected with pathogenic and nonpathogenic molecular clones of SIV. The concentration of CSF quinolinic acid, a marker of intrathecal immune and macrophage activation, was examined concurrently. We found that significant increases in the density of perivascular macrophages/microglia coincided with viral neuroinvasion and marked elevations in CSF quinolinic acid. Furthermore, combined in situ hybridization and immunohistochemistry demonstrated that infected perivascular cells were macrophages/microglia. These findings provide evidence suggesting that neuroinvasion occurs through an influx of infected monocytes which take up residence in the CNS as perivascular macrophages/microglia. VCAM-1 expression, however, was not clearly correlated with these events, thus its contribution to initial viral neuroinvasion is unclear. C1 HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. COLORADO STATE UNIV,COLL VET MED,FT COLLINS,CO 80523. UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616. NIMH,BETHESDA,MD 20892. FU NCRR NIH HHS [RR07000]; NINDS NIH HHS [NS30769]; PHS HHS [A25644] NR 45 TC 116 Z9 117 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1996 VL 2 IS 6 BP 423 EP 432 DI 10.3109/13550289609146909 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA WA335 UT WOS:A1996WA33500008 PM 8972425 ER PT J AU Namboodiri, AMA Venkateshan, CNS Narayanan, R Blinder, K Moffett, JR Gajdusek, DC Gravell, M Gibbs, CJ AF Namboodiri, AMA Venkateshan, CNS Narayanan, R Blinder, K Moffett, JR Gajdusek, DC Gravell, M Gibbs, CJ TI Increased quinolinate immunoreactivity in the peripheral blood monocytes/macrophages from SIV-infected monkeys SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE quinolinic acid; tryptophan; kynurenine; excitotoxicity; lentivirus ID SIMIAN IMMUNODEFICIENCY VIRUS; PULMONARY INDOLEAMINE 2,3-DIOXYGENASE; BACTERIAL LIPOPOLYSACCHARIDE; TRYPTOPHAN-METABOLISM; CEREBROSPINAL-FLUID; RHESUS MACAQUES; IMMUNE-SYSTEM; MOUSE LUNG; ACID; CELLS AB Quinolinate (QUIN), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that is thought to act through the NMDA receptor system, was localized in cultured peripheral blood monocytes/macrophages from SIV-infected monkeys using a recently developed immunohistochemical method. Significant increases in QUIN immunoreactive (IR) cells were detected in all five SIV-infected monkeys examined. Multinucleated giant cells, a hallmark of lentiviral infection, were visible in selected samples. Treatment with the QUIN precursors, tryptophan and kynurenine, increased the number of QUIN-IR cells in both the control and SIV-infected preparations, perhaps by a mass action mechanism. We hypothesize that in SIV-infected monkeys, infiltrating monocytes/macrophages contribute to the high level of brain QUIN and associated neuropathology. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT BIOL,WASHINGTON,DC 20057. NINCDS,LAB MOL MED & NEUROSCI,MOL MED & VIROL SECT,NIH,BETHESDA,MD 20892. NR 31 TC 13 Z9 13 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1996 VL 2 IS 6 BP 433 EP 438 DI 10.3109/13550289609146910 PG 6 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA WA335 UT WOS:A1996WA33500009 PM 8972426 ER PT J AU Lee, KS He, XS Jones, DW Coppola, R Gorey, JG Knable, MB deCosta, BR Rice, KC Weinberger, DR AF Lee, KS He, XS Jones, DW Coppola, R Gorey, JG Knable, MB deCosta, BR Rice, KC Weinberger, DR TI An improved method for rapid and efficient radioiodination of iodine-123-IQNB SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE iodine-123-IQNB; diastereomers; muscarinic receptors; SPECT ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; IN-VIVO SELECTIVITY; KINETIC-ANALYSIS; 3-QUINUCLIDINYL 4-IODOBENZILATE; POTENTIAL RADIOPHARMACEUTICALS; QUINUCLIDINYL BENZILATE; ALZHEIMERS-DISEASE; M2 SUBTYPE; RAT-BRAIN; INVIVO AB The SPECT radioligand, 3-quinuclidinyl-4-[I-123]iodobenzilate ([I-123]IQNB), binds to muscarinic receptors and has generated interest as a potential agent for clinical SPECT. Unfortunately, cumbersome and inefficient radioiodination procedures have limited the practicality of [I-123]IQNB SPECT imaging. Methods: We report a rapid (5 min) and simple radioiodination procedure for preparing [I-123]IQNB from a tri-n-butylstannyl precursor in a no-carrier-added reaction that yields high specific activity with radiochemical yield exceeding 60%. The radiochemical purity of the final product exceeds 95%. Results: We have used this procedure to radioiodinate the four stereoisomers of [I-123]IQNB. The procedure is highly reliable and reproducible. SPECT studies on a healthy human volunteer at 1, 2, 6 and 24 hr after injection of each of the four stereoisomers reveal expected differences in the kinetic and binding characteristics of the four stereoisomers. (R,S)-[I-123]IQNB appears to be the SPECT agent of choice. Conclusion: Radioiodination of [I-123]IQNB from our tri-n-butylstannyl precursor is simpler, more efficient and less expensive than previous techniques. The potential exists for a ''kit'' which would be practical in a typical clinical setting. C1 NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. RP Lee, KS (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032, USA. NR 26 TC 18 Z9 18 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1996 VL 37 IS 12 BP 2021 EP 2024 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VY988 UT WOS:A1996VY98800032 PM 8970527 ER PT J AU Parker, JA Yester, MV DaubeWitherspoon, ME ToddPokropek, AE Royal, HJ AF Parker, JA Yester, MV DaubeWitherspoon, ME ToddPokropek, AE Royal, HJ TI Procedure guideline for general imaging: 1.0 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE practice guidelines; nuclear medicine imaging C1 BETH ISRAEL HOSP, BOSTON, MA 02215 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET ADM MED CTR, LOS ANGELES, CA 90024 USA. NIH, BETHESDA, MD 20892 USA. UCL, LONDON, ENGLAND. WASHINGTON UNIV, MED CTR, MALLINCKRODT INST RADIOL, ST LOUIS, MO 63110 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1996 VL 37 IS 12 BP 2087 EP 2092 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VY988 UT WOS:A1996VY98800045 PM 8970540 ER PT J AU Mettler, FH Becker, DV Wachholz, BW Bouville, AC AF Mettler, FH Becker, DV Wachholz, BW Bouville, AC TI Chernobyl: 10 years later SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID THYROID-CANCER; RADIATION C1 NCI,RADIAT EFFECTS BRANCH,NIH,BETHESDA,MD 20892. RP Mettler, FH (reprint author), HLTH SCI CTR,DEPT RADIOL & NUCL MED,ALBUQUERQUE,NM, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1996 VL 37 IS 12 BP N24 EP & PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VY988 UT WOS:A1996VY98800003 PM 8970506 ER PT J AU Slesinski, MJ Subar, AF Kahle, LL AF Slesinski, MJ Subar, AF Kahle, LL TI Dietary intake of fat, fiber and other nutrients is related to the use of vitamin and mineral supplements in the United States: The 1992 National Health Interview Survey SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 95 Meeting CY APR 09-13, 1995 CL ATLANTA, GA SP Federat Amer Soc Exptl Biol DE dietary intake; vitamin supplements; calcium supplements; National Health Interview Survey; humans ID NHANES-II SURVEY; QUANTITATIVE DATA; AMERICAN DIET; MORTALITY; POPULATION; NUTRITION; CANCER AB Supplement intake is hypothesized to increase the risk of some diseases while decreasing the risk of others. Both diet and lifestyle behaviors, however, may be associated with supplement use and confound observed associations. Nutrient intake from a food frequency questionnaire, demographic characteristics and lifestyle among supplement users and non-users were examined in 11,643 adults who participated in the 1992 National Health Interview Survey Epidemiology Supplement. Forty-six percent reported taking a supplement in the past year; 24% reported daily use. Daily use was highest among women, whites, those 75 y of age or older, those at or above the poverty level, those with more than 12 y of education, former smokers, and light drinkers consuming less than one alcoholic beverage per week. When controlled for sociodemographic factors, smoking status and drinking habits, there were no significant (P < 0.01) differences in dietary nutrient intake between daily and occasional supplement users. Compared with those of nonusers, diets of vitamin supplement users were lower (P < 0.001) in fat and higher in fiber and vitamins A and C for both men and women and higher in Vitamin E and calcium for women only. In general, diet, demographic and lifestyle characteristics of supplement users are typical of patterns associated with low risk of chronic disease. C1 NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD 20904 USA. NR 36 TC 77 Z9 77 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 1996 VL 126 IS 12 BP 3001 EP 3008 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WD494 UT WOS:A1996WD49400008 PM 9001367 ER PT J AU Bjornson, AB Falletta, JM Verter, JI Buchanan, GR Miller, ST Pegelow, CH Iyer, RV Johnstone, HS DeBaun, MR Wethers, DL Wang, WC Woods, GM Holbrook, CT Becton, DL Kinney, TR Reaman, GH Kalinyak, K Grossman, NJ Vichinsky, E Reid, CD AF Bjornson, AB Falletta, JM Verter, JI Buchanan, GR Miller, ST Pegelow, CH Iyer, RV Johnstone, HS DeBaun, MR Wethers, DL Wang, WC Woods, GM Holbrook, CT Becton, DL Kinney, TR Reaman, GH Kalinyak, K Grossman, NJ Vichinsky, E Reid, CD TI Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: Effects of continued penicillin prophylaxis SO JOURNAL OF PEDIATRICS LA English DT Article ID INFLUENZAE TYPE-B; STREPTOCOCCUS-PNEUMONIAE; WALL POLYSACCHARIDE; OPSONIC ACTIVITY; DISEASE; IMMUNIZATION; SERUM; INFECTION; RADIOIMMUNOASSAY; STANDARDIZATION AB Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design: Children with sickle cell anemia, who had been treated with prophylactic penicillin for at least 2 years before their fifth birthday, were randomly selected at age 5 years to continue penicillin prophylaxis or to receive placebo treatment, These children had been immunized once or twice in early childhood with pneumococcal polysaccharide vaccine and were reimmunized at the time of randomization. Results: Serotype-specific IgG antibody responses to reimmunization varied according to pneumococcal serotype but in general were mediocre or poor; the poorest response was to serotype 6B. The antibody responses were similar in subjects with continued penicillin prophylaxis or placebo treatment, and in subjects who received one or two pneumococcal vaccinations before reimmunization. The occurrence of pneumococcal bacteremia was associated with low IgG antibody concentrations to the infecting serotype. Conclusions: Reimmunization of children with sickle cell anemia who received pneumococcal polysaccharide vaccine at age 5 years induces limited production of serotype-specific IgG antibodies, regardless of previous pneumococcal vaccine history, Continued penicillin prophylaxis does not interfere with serotype-specific IgG antibody responses to reimmunization. C1 DUKE UNIV, MED CTR, DIV PEDIAT HEMATOL ONCOL, DUKE COMPREHENS SICKLE CELL CTR, DURHAM, NC 27710 USA. JAMES N GAMBLE INST MED RES, DIV IMMUNOL, CINCINNATI, OH USA. GEORGE WASHINGTON UNIV, CTR BIOSTAT, ROCKVILLE, MD USA. UNIV TEXAS, SW MED CTR, DEPT PEDIAT, DALLAS, TX USA. SUNY HLTH SCI CTR, BROOKLYN, NY 11203 USA. UNIV MIAMI, DEPT PEDIAT, MIAMI, FL 33152 USA. UNIV MISSISSIPPI, DIV PEDIAT HEMATOL ONCOL, JACKSON, MS 39216 USA. UNIV ILLINOIS, DEPT PEDIAT, CHICAGO, IL USA. WASHINGTON UNIV, SCH MED, DIV PEDIAT HEMATOL ONCOL, ST LOUIS, MO USA. ST LUKES ROOSEVELT HOSP, SICKLE CELL CTR, NEW YORK, NY USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA. CHILDRENS MERCY HOSP, HEMATOL ONCOL SECT, KANSAS CITY, MO 64108 USA. CHILDRENS HOSP EASTERN N CAROLINA, DIV PEDIAT HEMATOL ONCOL, GREENVILLE, NC USA. ARKANSAS CHILDRENS HOSP, DIV PEDIAT HEMATOL ONCOL, LITTLE ROCK, AR 72202 USA. CHILDRENS HOSP, NATL MED CTR, DIV HEMATOL ONCOL, WASHINGTON, DC 20010 USA. CHILDRENS HOSP, MED CTR, CTR COMPREHENS SICKLE CELL, CINCINNATI, OH 45229 USA. COLUMBUS CHILDRENS HOSP, DIV PEDIAT HEMATOL ONCOL, COLUMBUS, OH USA. CHILDRENS HOSP OAKLAND, DEPT HEMATOL, OAKLAND, CA 94609 USA. NHLBI, DIV BLOOD DIS & RESOURCES, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [N01-HB-87050] NR 35 TC 21 Z9 23 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 1996 VL 129 IS 6 BP 828 EP 835 DI 10.1016/S0022-3476(96)70026-4 PG 8 WC Pediatrics SC Pediatrics GA VY343 UT WOS:A1996VY34300012 PM 8969724 ER PT J AU Barber, JP Frank, A Weiss, RD Blaine, J Siqueland, L Moras, K Calvo, N Chittams, J Mercer, D Salloum, IM AF Barber, JP Frank, A Weiss, RD Blaine, J Siqueland, L Moras, K Calvo, N Chittams, J Mercer, D Salloum, IM TI Prevalence and correlates of personality disorder diagnoses among cocaine dependent outpatients SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID ADDICTION SEVERITY INDEX; SUBSTANCE-ABUSERS; PILOT TRIAL; DEPRESSION; DESIPRAMINE; ALCOHOL AB This paper reports on the prevalence and the pretreatment psychiatric, drug use, and demographic correlates of DSM-III-R personality disorders (PD) in a sample of 289 cocaine dependent outpatients accepted into the pilot phase of a randomized, multisite, clinical trial comparing different psychotherapy and drug counseling treatment modalities. Diagnoses were established using the SCID, administered to patients after a brief drug free period by highly experienced evaluators. Results showed that 48% of the patients had at least one PD and 18% had two or more. Of those with a PD, 65% had a Cluster B disorder with antisocial (APD) and borderline (BPD) PD being the most common, Men were significantly more likely to be diagnosed with APD than women, but no other gender differences were found, Patients with PDs were significantly more likely to receive another Axis 1 diagnosis and to have more severe psychiatric symptoms than patients without PDs. However, the groups did not differ on other measures of drug use severity or demographic variables, Additional subgroup analyses showed that patients with comorbid BPD had the highest level of depression, and patients who had both APD and BPD were more functionally impaired than patients with no PD. While the prognostic significance of these findings remains unclear, the results suggest that personality disorders are apt to play an important role in the treatment of cocaine dependence, and should be incorporated into the development of future treatments and research studies. C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. NIDA,DIV CLIN & RES SERV,TREATMENT RES BRANCH,LEXINGTON,KY 40583. OI barber, jacques/0000-0002-8762-2595 NR 37 TC 17 Z9 17 U1 1 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD WIN PY 1996 VL 10 IS 4 BP 297 EP 311 PG 15 WC Psychiatry SC Psychiatry GA WD285 UT WOS:A1996WD28500001 ER PT J AU Brauneis, U Oz, M Peoples, RW Weight, FF Zhang, L AF Brauneis, U Oz, M Peoples, RW Weight, FF Zhang, L TI Differential sensitivity of recombinant N-methyl-D-aspartate receptor subunits to inhibition by dynorphin SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID OPIOID PEPTIDE DYNORPHIN; GUINEA-PIG HIPPOCAMPUS; CA3 PYRAMIDAL CELLS; NMDA RECEPTOR; SPINAL-CORD; DENTATE GYRUS; KAPPA-OPIOIDS; RAT; POTENTIATION; GLUTAMATE AB Dynorphin is an endogenous ligand for kappa-opioid receptors. We investigated the effect of dynorphin 1-13 on different heteromeric subunits of recombinant mouse N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes by using voltage-clamp recording methods. Dynorphin inhibited the NMDA-activated currents of all heteromeric NMDA receptor subunits tested. The different NMDA receptor subunits, however, exhibited a differential sensitivity to dynorphin. For the epsilon-1/zeta-1 subunit combination the EC(50) was 19 mu M; the other NMDA receptor subunit combinations were less sensitive to dynorphin and had the following order of sensitivity: epsilon-2/zeta-1 > epsilon-4/zeta-1 > epsilon-3/zeta-1. Inhibition of NMDA-activated currents by dynorphin was not competitive with NMDA, and was voltage-independent. NMDA-activated currents were not affected by the synthetic kappa-opioid receptor agonist U50488 {trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzene-acetamide}, the specific kappa-opioid receptor antagonist nor-binaltorphimine(1) or the nonspecific opioid receptor antagonist naloxone. In addition, nor-binaltorphimine, or naloxone did not attenuate dynorphin inhibition of NMDA-activated current. The observations suggest that dynorphin inhibition of NMDA receptor function is mediated by an interaction of dynorphin with NMDA receptors, rather than an action involving kappa-opioid receptors. The data also show that different heteromeric NMDA receptor subunits exhibit a differential sensitivity to dynorphin. C1 NIAAA,MOL & CELLULAR NEUROBIOL LAB,NIH,BETHESDA,MD. RI Oz, Murat/E-2148-2012 NR 41 TC 23 Z9 23 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 DEC PY 1996 VL 279 IS 3 BP 1063 EP 1068 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VY207 UT WOS:A1996VY20700001 PM 8968325 ER PT J AU Schetz, JA Calderon, SN Bertha, CM Rice, K Porreca, F AF Schetz, JA Calderon, SN Bertha, CM Rice, K Porreca, F TI Rapid in vivo metabolism of a methylether derivative of (+/-)-BW373U86: The metabolic fate of [H-3]SNC121 in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID OPIOID RECEPTOR AGONIST; BW373U86; SNC-80; MOUSE; BRAIN AB Activation of opioid delta receptors produces antinociception without some of the side-effects associated with activation of mu and kappa receptors. (+/-)-BW373U86 {(+/-)-4-[(alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl]-N,N-diethylbenzamide} is a first generation, racemic nonpeptide, partially delta-selective opioid agonist that produces short-lived antinocioception. After systemic, but not central, administration, (+/-)-BW373U86 is also a naltrindole-reversible convulsant. SNC80 {(+)-4-[9-alpha-R)-alpha-((2S,5R0-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide} is a chiral methylether derivative of (+/-)-BW373U86 with decreased potency, but greater selectivity for the delta-opioid receptor. Like BW373U86, SNC80 produces brief, nonlethal seizures when administered peripherally, albeit at higher doses. Radiolabeling of SNC80 yields a compound with similar pharmacology named [H-3]SNC121. [H-3]SNC121 was investigated to determine the relationship between its time course of metabolism and the physiological actions of SNC80. The biotransformation of i.p. administered [H-3]SNC121 was established in rats in vivo and in vitro via high-performance liquid chromatography analysis of extracted radioactive tissues and fluids. Radioactive equivalents were characterized by their high-performance liquid chromatography retention times and opioid binding activity in rat brain membranes. The kidney, and especially the liver (within 5 min), rapidly metabolize SNC121 to a metabolite with delta-opioid activity coeluting with BW373U86. Direct i.c.v. administration of [H-3]SNC121 resulted in minimal metabolism after 1 hr. We conclude that i.p., but not i.c.v., administered [H-3]SNC121 can be metabolized rapidly and substantially by the liver to a BW373U86-like compound. The in vivo time course of metabolism after i.p. administration of [H-3]SNC121 is consistent with the duration of SNC80 antinociception, and the rapid formation of a BW373U86-like metabolite may also account, in part, for its convulsant properties. C1 UNIV ARIZONA,COLL MED,DEPT PHARMACOL,TUCSON,AZ. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. FU NIDA NIH HHS [DA00185] NR 15 TC 14 Z9 14 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1996 VL 279 IS 3 BP 1069 EP 1076 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VY207 UT WOS:A1996VY20700002 PM 8968326 ER PT J AU Evans, SM Cone, EJ Henningfield, JE AF Evans, SM Cone, EJ Henningfield, JE TI Arterial and venous cocaine plasma concentrations in humans: Relationship to route of administration, cardiovascular effects and subjective effects SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INTRAVENOUS COCAINE; CIGARETTE-SMOKING; NICOTINE; BLOOD; BASE; PHARMACOKINETICS; COCAETHYLENE; TOLERANCE AB Arterial plasma drug concentrations should be a strong predictor of resultant physiological and behavioral effects of smoked drugs. Nine healthy male volunteers, who were current users of smoked and i.v. cocaine, participated in a study directly comparing arterial and venous cocaine plasma concentrations after smoked and i.v. cocaine. Each volunteer was first tested under all dosing conditions without an arterial catheter (phase I), to determine whether subjects could tolerate each cocaine dose, before testing with an arterial catheter (phase II). Phase II consisted of two test days, each consisting of either four smoked-cocaine sessions (sham, 12.5, 25 and 50 mg) or four i.v. cocaine sessions (0, 8, 16 and 32 mg) in ascending order, spaced 90 min apart. For the two highest doses for each route, arterial and venous blood samples were taken simultaneously before drug administration, during drug administration and frequently after drug administration. At the same time, cardiovascular effects and subjective effects were measured. Arterial cocaine concentrations were substantially higher than venous cocaine concentrations after both routes of cocaine administration. After either smoked or i.v. cocaine, maximal arterial cocaine concentrations occurred within 15 sec, whereas maximal venous cocaine concentrations occurred within 4 min. The onset of cardiovascular and subjective effects was also rapid, and arterial cocaine concentrations tended to account for these effects to a greater extent than did venous cocaine concentrations. Even though arterial and venous cocaine concentrations were lower after smoked cocaine, compared with i.v. cocaine, the magnitudes of cardiovascular and subjective effects were similar, suggesting that smoked cocaine may produce a greater effect at similar concentrations. These findings do not support the hypothesis that the greater effects observed after smoking are a result of smoked cocaine reaching the brain faster than i.v. cocaine, as measured by peripheral arterial plasma concentrations. C1 NIDA,CLIN PHARMACOL BRANCH,ADDICT RES CTR,NIH,BALTIMORE,MD 21224. NR 30 TC 125 Z9 128 U1 3 U2 5 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 DEC PY 1996 VL 279 IS 3 BP 1345 EP 1356 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VY207 UT WOS:A1996VY20700035 PM 8968359 ER PT J AU Masereeuw, R Saleming, WC Miller, DS Russel, FGM AF Masereeuw, R Saleming, WC Miller, DS Russel, FGM TI Interaction of fluorescein with the dicarboxylate carrier in rat kidney cortex mitochondria SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MEMBRANE-VESICLES; TRANSPORT; INHIBITION; AMINOHIPPURATE; VALPROATE; TUBULES; INVITRO; CELLS AB The interaction of the organic anion, fluorescein (FL), with mitochondria in renal proximal tubule cells was investigated. Confocal microscopy was used to demonstrate FL accumulation in mitochondria of intact cells. Phenylsuccinate inhibited the mitochondrial accumulation of the FL analog, carboxyfluorescein (CF) indicating that the dicarboxylate carrier may be involved in the intracellular compartmentation of organic anions. To char acterize the interaction, radio-tracer uptake and respiration studies with renal mitochondria were carried out using succinate as a substrate. Respiration measurements in freshly isolated kidney cortex mitochondria revealed that FL inhibited ADP-stimulated and uncoupled respiratory rate, indicating that the organic anion inhibited the availability of succinate as a reducing agent. A similar effect on mitochondrial respiration was found for PAH and phenylsuccinate. FL inhibited C-14-succinate uptake concentration-dependently, and Dixon analysis revealed that the nature of interaction between FL and succinate was competitive. K-i values of 0.5 +/- 0.2 and 1.1 +/- 0.8 mM were calculated for respiration experiments and tracer uptake studies, respectively. The data demonstrate that FL competitively interacts with a mitochondrial dicarboxylate transporter. C1 UNIV NIJMEGEN,FAC MED SCI,DEPT PHARMACOL,NL-6500 HB NIJMEGEN,NETHERLANDS. NIEHS,CELLULAR & MOL PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014; OI Russel, Frans/0000-0002-7959-2314; Masereeuw, Rosalinde/0000-0002-1560-1074 NR 25 TC 11 Z9 11 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 DEC PY 1996 VL 279 IS 3 BP 1559 EP 1565 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VY207 UT WOS:A1996VY20700059 PM 8968383 ER PT J AU Prete, SP Aquino, A Masci, G Orlando, L Giuliani, A DeSantis, S DeVecchis, L DeFilippi, R Greiner, JW Bonmassar, E Graziani, G AF Prete, SP Aquino, A Masci, G Orlando, L Giuliani, A DeSantis, S DeVecchis, L DeFilippi, R Greiner, JW Bonmassar, E Graziani, G TI Drug-induced changes of carcinoembryonic antigen expression in human cancer cells: Effect of 5-fluorouracil SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID COLON-CARCINOMA-CELLS; HUMAN RECOMBINANT INTERFERONS; MESSENGER-RNA; GAMMA-INTERFERON; MONOCLONAL-ANTIBODIES; NUCLEAR-RNA; TUMOR-CELLS; GENE; EPITOPES; INVIVO AB Previous studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivity of the human colon carcinoma cell line HT-29 with a monoclonal antibody (COL-I) directed against carcinoembryonic antigen (CEA). In the present study, we show that short-term exposure (i.e., 1 hr) of cancer cells to 5-FU mediates a marked increase of CEA expression, that is concentration-dependent and lasts up to day 5 after treatment. This phenomenon is the result of the drug-mediated enhancement of the CEA expression, but not of the selection of the CEA-positive cells operated by the antimetabolite. This is supported by the finding that the increase of the CEA expression detected by cytofluorimetric analysis is observed not only in the parental HT-29 line, but also in its C22.20 subclone, endowed with a low basal level of CEA and with chemosensitivity to 5-FU lower than that of the parental cell line. Moreover, increase of CEA expression occurs not only in the plasma membrane, but also in the cytosolic cellular compartment, as indicated by the results of Western blot analysis. Northern blot analysis of total RNA extracted from 5-FU-treated HT-29 or C22.20 cells shows an increase in the steady-state levels of CEA and CEA-related transcripts (e.g., biliary glycoprotein). Moreover 5-FU-mediated augmentation of the CEA transcript appears to be attributable mainly to enhanced transcription rather than to increased mRNA stability. it is concluded that induction of enhanced CEA protein expression in cancer cells treated with 5-FU could be of clinical interest for the development of immunochemotherapeutic protocols based on CEA protein as the target molecule. C1 UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,I-00133 ROME,ITALY. CNR,INST EXPT MED,ROME,ITALY. NATL CANC INST,NATL INST HLTH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD. UNIV UDINE,DEPT PATHOL & EXPT & CLIN MED,I-33100 UDINE,ITALY. IST RICOVERO & CURA CARATTERE SCI,IST DERMOPAT IMMACOLATA,ROME,ITALY. RI Graziani, Grazia/G-5747-2012; OI GRAZIANI, GRAZIA/0000-0002-0221-768X NR 47 TC 16 Z9 16 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1996 VL 279 IS 3 BP 1574 EP 1581 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VY207 UT WOS:A1996VY20700061 PM 8968385 ER PT J AU Rho, JM Donevan, SD Rogawski, MA AF Rho, JM Donevan, SD Rogawski, MA TI Direct activation of GABA(A) receptors by barbiturates in cultured rat hippocampal neurons SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GAMMA-AMINOBUTYRIC ACID; MOUSE SPINAL NEURONS; KINETIC-PROPERTIES; CORD NEURONS; DIFFERENT MECHANISMS; CONDUCTANCE STATE; CHLORIDE CHANNELS; PICROTOXIN BLOCK; RESPONSES; ENHANCEMENT AB 1. The direct activation of the GABA(A) receptor by pentobarbitone (PB) and phenobarbitone (PHB) was characterized in cultured rat hippocampal neurons using whole-cell voltage clamp and single channel recording techniques. 2. In whole-cell recordings, PB and PHB produced a concentration-dependent activation of Cl- current (EC(50) values, 0.33 and 3.0 mM, respectively). The response to the barbiturates was similar to that produced by GABA, although GABA was more potent (EC(50), 5.5 mu M). PB and PHB were substantially more potent in enhancing the response to 1 mu M GABA (EC(50) values, 94 mu M and 0.89 mM, respectively). The maximal magnitude of the responses to PB was similar to that of the maximal response to GABA or GABA + PB. PHB appeared to be modestly less efficacious. 3. The mean deactivation time constant for whole-cell Cl- currents evoked by 1 mM PB + 1 mu M GABA was significantly longer (480 +/- 34 ms) than for 1 mM PB (170 +/- 9 ms) or 1 mu M GABA (180 +/- 14 ms) alone. 4. Whole-cell currents directly activated by 300 mu M PB and 1 mu M GABA were blocked by the GABA receptor antagonists bicuculline and picrotoxin. 5. Unitary GABA, receptor channel currents evoked by 300 mu M PB had similar main conductance, mean open time and mean burst duration as those activated by 2 mu M GABA alone. Single channel openings and bursts were of shorter mean duration when 100 and 300 mu M PHB mere used. 6. High concentrations of PB (1-3 mM) and PHB (3-10 mM) produced a rapid block of currents activated by the barbiturate alone or by the barbiturate in the presence of 1 mu M GABA. The estimated IC50 values for block of PB- and PHB-potentiated GABA currents were 2.8 and 12. 9 mM, respectively. 7. Single channel currents activated by high concentrations of PB and PHB alone or in the presence of GABA demonstrated flickering, probably reflecting fast channel block. 8. We conclude that the gating of the GABA, receptor channel by PHB and PB is functionally similar to that produced by the natural agonist GABA alone, but distinct from that obtained when barbiturates modulate the response to GABA. At high concentrations, the barbiturates produce a channel blocking action that limits the maximum total current conducted by the channel. C1 NINCDS,NEURONAL EXCITABILITY SECT,EPILEPSY RES BRNACH,NIH,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 35 TC 118 Z9 118 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 1996 VL 497 IS 2 BP 509 EP 522 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VY213 UT WOS:A1996VY21300016 PM 8961191 ER PT J AU Siegal, MD Garcia, AI Kandray, DP Giljahn, LK AF Siegal, MD Garcia, AI Kandray, DP Giljahn, LK TI The use of dental sealants by Ohio dentists SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE pit and fissure sealants; sealant promotion; dental caries prevention ID FISSURE SEALANTS; PRIVATE-PRACTICE; CARIES; PIT; PRACTITIONERS; USAGE AB Objectives: To assess the extent to which Ohio dentists report using pit and fissure sealants and factors associated with sealant use. Methods: A mail survey of a random sample of Ohio dentists was conducted in 1989 and repeated in 1992 with a newly drawn sample. Only responses from general dentists were analyzed using univariate analyses and multiple regression. Results: Dentists who reported using sealants increased from 79.4 percent in 1989 to 91.8 percent in 1992. In 1992, 42.9 percent were low-level users (<15% of school-aged patients), 41.7 percent were moderate-level users (15-39%), and 15.3 percent were high-level users (>39%). Over three-fourths of sealant-using dentists expressed some degree of willingness to seal incipient caries. The level of sealant use was associated with dentists' knowledge about sealants, conservative management of dental caries, number of children seen in the practice, and influence of insurance coverage for sealants. The regression model explained 22.0 percent of the variance. Clinical factors associated with the level of use were: dentists' willingness to seal premolars; caries-free teeth; teeth with deep, narrow pits and fissures; teeth with small, frank occlusal caries and patients 18 years of age or older. This regression model explained only 15.1 percent of the variance. Conclusions: The great majority of Ohio dentists report using sealants. The percent of reported sealant users increased between 1989 and 1992. Ohio dentists are not consistent with regard to the percent of their child patients for whom they apply sealants or their willingness to seal incipient caries. Dentists continue to identify lack of insurance coverage for sealant application as a major barrier to patients receiving the service. C1 OHIO DEPT HLTH,BUR HLTH SERV INFORMAT & OPERAT SUPPORT,COLUMBUS,OH 43266. NIDR,BETHESDA,MD 20892. YOUNGSTOWN STATE UNIV,ALLIED HLTH DEPT,DENT HYG PROGRAM,YOUNGSTOWN,OH 44555. RP Siegal, MD (reprint author), OHIO DEPT HLTH,BUR DENT HLTH,246 N HIGH ST,COLUMBUS,OH 43266, USA. NR 54 TC 13 Z9 13 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1996 VL 56 IS 1 BP 12 EP 21 DI 10.1111/j.1752-7325.1996.tb02389.x PG 10 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA UA138 UT WOS:A1996UA13800004 PM 8667312 ER PT J AU Andrews, NP Gralnick, HR Merryman, P Vail, M Quyyumi, AA AF Andrews, NP Gralnick, HR Merryman, P Vail, M Quyyumi, AA TI Mechanisms underlying the morning increase in platelet aggregation: A flow cytometry study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SUDDEN CARDIAC DEATH; PROTHROMBIN FRAGMENT 1+2; WHOLE-BLOOD; CIRCADIAN VARIATION; MYOCARDIAL-INFARCTION; FIBRINOLYTIC-ACTIVITY; ACTIVATED PLATELETS; ADRENALINE INFUSION; UPRIGHT POSTURE; HEART-DISEASE AB Objectives. Mechanisms underlying the morning increase in platelet aggregation produced by arising and assuming the upright posture were studied by examining 1) the expression on the platelet surface of activation dependent markers; 2) platelet aggregation in whole blood; and 3) hematologic factors likely to influence aggregation. Background. The morning increase in thrombotic cardiovascular events has been attributed, in part, to the morning surge in platelet aggregability, but its mechanisms are poorly understood. Methods. Expression of seven platelet surface antigens (including P-selectin, activated GPIIb-IIIa and GPIb-IX), whole-blood platelet aggregation, platelet count and hematocrit were measured before and after arising in 17 normal volunteers. The fibrinolytic variables, tissue-type plasminogen activator, plasminogen activator inhibitor I and catecholamine levels were also measured. Results. On arising and standing, platelet aggregation increased by 71% (p < 0.01) and 27% (p < 0.03) in response to collagen and adenosine diphosphate, respectively. However, there was no change in any of the activation-dependent platelet surface markers. Whole-blood platelet count and hematocrit increased by 15% and 7% (both p < 0.0001), respectively. Norepinephrine and epinephrine levels increased by 189% (p < 0.0001) and 130% (p < 0.01), respectively. Tissue-type plasminogen activator antigen increased (31%, p < 0.01), but there was no significant increase in plasminogen activator inhibitor 1, suggesting an overall increase in fibrinolysis on standing. Prothrombin fragment 1.2 increased by 28% (p < 0.02), indicating a small increase in thrombin generation. The increases in hematocrit and platelet count that occurred on standing were carefully mimicked in vitro and resulted in a 115% (p < 0.05) increase in platelet aggregation in response to adenosine diphosphate. Conclusions. These data demonstrate that the morning increase in platelet aggregation is not accompanied by expression of activation-dependent platelet surface receptors and suggest that the increase in whole blood aggregation may be primarily due to the increases in catecholamine levels, platelet count and hemoconcentration. (C) 1996 by the American College of Cardiology C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,SERV HEMATOL,BETHESDA,MD 20892. NR 47 TC 40 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1996 VL 28 IS 7 BP 1789 EP 1795 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VY325 UT WOS:A1996VY32500022 PM 8962568 ER PT J AU Nebeling, LC Forman, MR Graubard, BI Snyder, RA AF Nebeling, LC Forman, MR Graubard, BI Snyder, RA TI Specific and total carotenoid intakes among oral contraceptive and estrogen hormone users in the United States SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE diet survey; carotenoid; oral contraceptive; estrogen; hormone; risk ID FOOD-COMPOSITION DATABASE; BREAST-CANCER; REPLACEMENT THERAPY; VITAMIN-E; PREMENOPAUSAL WOMEN; SUBSEQUENT CANCER; BETA-CAROTENE; RISK; DIETARY; VEGETABLES AB Objective: To compare carotenoid intakes between hormone users and nonusers in a nationally representative sample of US women by demographic and lifestyle characteristics and to identify those with potentially greater risk for disease. Design: Data from the 1987 National Health Interview Survey's-Epidemiology Supplement food frequency questionnaire were linked to the USDA-NCI Carotenoid database to estimate mean total and specific carotenoid intakes. Subjects: Women (n = 8,962) were grouped by menopausal status and classified by hormone use into premenopausal oral contraceptive users/nonusers (n = 5,918) and postmenopausal estrogen replacement hormone users/nonusers (n = 3,044). Statistical Analyses Performed: Mean carotenoid intakes and standard errors were weighted using SUDAAN and adjusted for potential confounding factors using multiple linear regression analysis. Statistically significant differences were at p values <0.01. Results: Compared to nonusers, oral contraceptive users had lower specific carotenoid intakes. Demographic and lifestyle characteristics differed between oral contraceptive users/nonusers and were examined in relation to carotenoid intakes. More oral contraceptive users than nonusers were married, highly educated, drank alcoholic beverages, and smoked. After adjustment for these factors in a multiple linear regression model, the associations between oral contraceptive use and carotenoid intake remained statistically significant. Mean carotenoid intakes were not significantly different among estrogen hormone replacement users versus nonusers. Conclusions: Oral contraceptive users have lower dietary carotenoid intakes than nonusers. Since oral contraceptive users smoke and drink more than nonusers, and both factors are associated with lower carotenoid intakes, oral contraceptive users form a potential high risk group for disease. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Nebeling, LC (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,SUITE 211,6130 EXECUT BLVD,MSC 732,BETHESDA,MD 20892, USA. NR 41 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD DEC PY 1996 VL 15 IS 6 BP 608 EP 613 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VV298 UT WOS:A1996VV29800009 PM 8951739 ER PT J AU Slavkin, HC AF Slavkin, HC TI Infection and immunity SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 DEC PY 1996 VL 127 IS 12 BP 1792 EP 1796 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VX672 UT WOS:A1996VX67200029 PM 8990752 ER PT J AU VandenLangenberg, GM Brady, WE Nebeling, LC Block, G Forman, M Bowen, PE StacewiczSapuntzakis, M MaresPerlman, JA AF VandenLangenberg, GM Brady, WE Nebeling, LC Block, G Forman, M Bowen, PE StacewiczSapuntzakis, M MaresPerlman, JA TI Influence of using different sources of carotenoid data in epidemiologic studies SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT Experimental Biology 96 Meeting CY APR 14-18, 1996 CL WASHINGTON, DC ID FOOD-COMPOSITION DATABASE; DIETARY-INTAKE; QUESTIONNAIRE; VEGETABLES; WOMEN; CANCER; FRUITS AB Objective This study compared distributions of carotenoid intake and diet-serum correlations using two sources of carotenoid data: the US Department of Agriculture-National Cancer Institute (USDA-NCI) carotenoid food composition database and values accompanying the Block-NCI Health Habits and History Questionnaire (HHHQ). Design and subjects A 100-item food frequency questionnaire was used to collect dietary data from 2,152 adults, aged 43 to 85 years, who were participating in the Nutritional Factors in Eye Disease Study, a population-based study designed to evaluate nutritional factors associated with age-related eye disease. Blood samples were collected from a random sample of 400 nonfasting participants in the study. Results Median carotenoid intakes using HHHQ vs USDA-NCI data were alpha carotene (229 vs 223 mu g/day), beta carotene (1,321 vs 1,325 mu g/day), beta cryptoxanthin (72 vs 21 mu g/day), lutein + zeaxanthin (653 vs 811 mu g/day), and lycopene (593 vs 1,615 mu g/day). Ail paired differences in carotenoid intake were significantly different from zero (Wilcoxon signed-rank, P<.0001). Despite these differences, the two databases similarly ranked individuals according to carotenoid intake: Spearman correlations ranged from .71 (lycopene) to .93 (alpha carotene). Differences between diet-serum correlations (adjusted for energy, body mass index, high density Lipoprotein, and total cholesterol) using HHHQ vs USDA-NCI data were minor and not significant (P>.05): alpha carotene (r=.33 vs.32), beta carotene (r=.27 vs.32), beta cryptoxanthin (r=.48 vs.53), lutein + zeaxanthin (r=.28 vs.24), and lycopene (r=.29 vs.25). Conclusions Although estimates of carotenoid intake differed significantly, only minor differences in carotenoid rankings and diet-serum correlations were observed using either data source in this population. C1 UNIV WISCONSIN,DEPT OPHTHALMOL & VISUAL SCI,MADISON,WI 53705. UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53705. UNIV WISCONSIN,DEPT PREVENT MED EPIDEMIOL,MADISON,WI 53705. NCI,BETHESDA,MD 20892. UNIV CALIF BERKELEY,BERKELEY,CA. UNIV ILLINOIS,DEPT NUTR & MED DIETET,CHICAGO,IL 60680. FU NEI NIH HHS [EYO-8012] NR 27 TC 43 Z9 44 U1 1 U2 3 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 DEC PY 1996 VL 96 IS 12 BP 1271 EP 1275 DI 10.1016/S0002-8223(96)00332-X PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WM906 UT WOS:A1996WM90600012 PM 8948389 ER PT J AU Langlois, JA Maggi, S Harris, T Simonsick, EM Ferrucci, L Pavan, M Sartori, L Enzi, G AF Langlois, JA Maggi, S Harris, T Simonsick, EM Ferrucci, L Pavan, M Sartori, L Enzi, G TI Self-report of difficulty in performing functional activities identifies a broad range of disability in old age SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID MINI-MENTAL-STATE; BODY-MASS INDEX; PHYSICAL-DISABILITY; RISK-FACTORS; FRAMINGHAM DISABILITY; MAINTAINING MOBILITY; VISUAL IMPAIRMENT; LATE-LIFE; NHANES-I; ELDERS AB OBJECTIVE: To describe a broad range of physical disability by examining the association between a four-level measure of disability, based on self-report of difficulty in performing functional activities, and previously identified risk factors for disability. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: A total of 2373 noninstitutionalized men and women aged 65 and older from the Veneto Region of Italy. MEASUREMENTS: Odds ratios for the association of the four levels of disability (none, mild, moderate, and ADL disability) differentiated by this new measure with known risk factors for physical disability. MAIN RESULTS: This summary measure of physical disability distinguished older persons with disability from the population typically classified as nondisabled. Twenty-one percent of study participants were identified as having Activities of Daily Living (ADL) disability (defined as self-report of difficulty in one or more ADLs), and an additional 40% had mild or moderate disability based on degree of difficulty in Instrumental Activities of Daily Living (IADLs) and physical functional activities. Hip fracture and lower extremity performance were strongly independently associated with each level of disability. The association of a range of established risk factors for disability and health care utilization measures with the levels of disability identified in our study, and the trend toward increasing odds with increasing disability, provide evidence of the construct validity of this measure. CONCLUSIONS: Self-report of difficulty in performing functional activities identifies older persons with physical disability not ascertained by self-report of the need for help, C1 NATL RES COUNCIL,TARGETED PROJECT AGING,FLORENCE,ITALY. OSPED I FRATICINI,NATL RES INST,INRCA,DEPT GERIATR,FLORENCE,ITALY. UNIV PADUA,INST INTERNAL MED,PADUA,ITALY. RP Langlois, JA (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 41 TC 54 Z9 54 U1 6 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1996 VL 44 IS 12 BP 1421 EP 1428 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VW457 UT WOS:A1996VW45700001 PM 8951310 ER PT J AU Ginns, SM Knepper, MA Ecelbarger, CA Terris, J He, XJ Coleman, RA Wade, JB AF Ginns, SM Knepper, MA Ecelbarger, CA Terris, J He, XJ Coleman, RA Wade, JB TI Immunolocalization of the secretory isoform of Na-K-Cl cotransporter in rat renal intercalated cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE Na-K-cl cotransport; intercalated cell; collecting duct; urinary acidification ID MEDULLARY COLLECTING DUCT; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; KIDNEY; MEMBRANE; LOCALIZATION; TRANSPORT; AMMONIUM AB Two bumetanide-sensitive ion cotransporters that carry Na+, K+, and Cl- in a coupled fashion have been identified. One type, the ''absorptive'' isoform, carries these ions across the apical plasma membrane of;the thick ascending limb of Henle's loop. Another isoform, the ''secretory'' cotransporter, has been identified in a number of epithelial tissues by physiological means, but its sites of expression in the kidney have not been fully characterized, Complementary DNA believed to code for the secretary isoform (called ''BSC2'' or ''NKCC1'') have recently been cloned, This study used a specific affinity-purified antipeptide antibody to this protein for immunolocalization in the rat kidney. Immunoblot studies using this antibody show abundant immunoreactivity against bands of 140-190 and 120 kd in the parotid gland, colon, and stomach, sites where the secretory form of the cotransporter has been identified by physiological techniques. This distribution supports the hypothesis that this isoform represents the secretory form of the cotransporter. Studies in the kidney revealed that the same bands are associated with membrane fractions chiefly in the outer medulla, Immunolocalizations show that immunoreactivity is selectively and intensely localized to the basolateral plasma membrane of a subfraction of outer medullary collecting duct cells. An independently produced monoclonal antibody (T4) specific for Na-K-Cl cotransporter displays the same localization. Dual localizations of cotransporter antibody with respect to antibody specific for principal cells (aquaporin-2) and intercalated cells (band 3 and H+-ATPase) show that cotransporter immunoreactivity is localized to alpha-intercalated cells of the outer medullary collecting duct in the rat. This distinctive localization suggests that the secretory form of the cotransporter may play a role in renal NH4+ and/or acid secretion by this cell type. C1 UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK-32839] NR 31 TC 74 Z9 76 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1996 VL 7 IS 12 BP 2533 EP 2542 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA VZ952 UT WOS:A1996VZ95200007 PM 8989731 ER PT J AU Levey, AS Caggiula, AW Greene, T Hunsicker, LG Kusek, JW Rogers, NL Teschan, PE AF Levey, AS Caggiula, AW Greene, T Hunsicker, LG Kusek, JW Rogers, NL Teschan, PE TI Effects of dietary protein restriction on the progression of moderate renal disease in the modification of diet in renal disease study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE clinical trial; dietary protein; GFR; progression; proteinuria ID DIABETIC NEPHROPATHY; FAILURE; INSUFFICIENCY; TRIAL; MICROALBUMINURIA; HEMODYNAMICS; EXPERIENCE AB The Modification of Diet in Renal Disease (MDRD) Study consisted of two randomized controlled trials to determine the effects of dietary protein restriction and strict blood pressure control. In 255 patients with advanced renal disease (baseline GFR, 13 to 24 mL/min per 1.73 m(2); Study B), secondary analyses demonstrated a correlation between achieved protein intake and rate of decline in GFR, consistent with a beneficial effect of a low-protein diet. In 585 patients with moderate renal disease (baseline GFR, 25 to 55 mL/min per 1.73 m(2); Study A), the primary analysis of the effect of the low-protein diet was inconclusive because of a nonlinear GFR decline and limited duration of follow-up. A meta-analysis of recent controlled trials, including MDRD Study A, demonstrated a beneficial effect of a low-protein diet on the incidence of renal failure. The objective of these secondary analyses is to explore further the effect of dietary protein restriction in Study A. In these analyses, a total of 585 patients were randomly assigned to follow either a low-protein diet (0.58 g/kg per day) or a usual-protein diet (1.3 g/kg day). Outcomes included the rate of GFR decline, incidence of renal failure or death, and change in urine protein excretion. Analyses included comparisons of randomized groups and correlations of outcomes with achieved protein intake. The comparisons of randomized groups revealed a faster GFR decline during the first 4 months after assignment to the low-protein diet but no difference in the variability in GFR decline between the diet groups, indicating a uniform short-term effect of the low-protein diet on GFR, probably as a result of hemodynamic adjustments. After 4 months, the mean decline in GFR in the low-protein diet group was slower, and the variability of the rate of decline was smaller, than in the usual-protein diet group (ratio of standard deviations, 0.73; 95% confidence interval, 0.55 to 0.91; P < 0.01). This suggests a greater beneficial effect of the low-protein diet in patients with a more rapid GFR decline. The net effect of the low-protein diet on GFR decline over 3 yr was no significant change in mean GFR decline, but reduced variability of the decline (ratio of standard deviations, 0.76; 95% confidence interval, 0.60 to 0.92; P < 0.01). Correlational analyses revealed trends similar to the comparisons of randomized groups. During the first 4 months, patients with a greater decline in protein intake (irrespective of diet group) had a greater decline in GFR; thereafter, patients with a lower protein intake had a slower GFR decline. Over 3 yr, there was no significant correlation between GFR decline and achieved protein intake. The correlation of protein intake with GFR decline after 4 months was less strong than observed in Study B. The relative risk of death or renal failure was 0.65 (95% confidence interval, 0.38 to 1.10; P = 0.10) in patients assigned to the low-protein diet group compared with the usual-protein diet group, which is similar to that observed in the meta-analysis. During follow-up, the increase in urine protein excretion was delayed in the low-protein diet group (P = 0.008) and in patients with lower achieved protein intake (P = 0.005). In summary, the absence of a significant difference between the diet groups in the mean change in GFR from baseline to 3 yr precludes a definitive conclusion of a beneficial effect of the diet intervention based solely on MDRD Study A. However, these secondary analyses are consistent with a beneficial effect of the low-protein diet to slow the GFR decline in patients with the most rapidly declining GFR and to reduce urine protein excretion. These results, together with the results of the recent meta-analysis (including MDRD Study A), provide some support for the hypothesis that dietary protein restriction slows the progression of moderate renal disease. C1 NIDDKD,NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,CTR MED,LOS ANGELES,CA 90024. UNIV PITTSBURGH,PITTSBURGH,PA 15260. EMORY UNIV,SCH MED,ATLANTA,GA 30322. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. UNIV IOWA,IOWA CITY,IA 52242. VANDERBILT UNIV,MED CTR,NASHVILLE,TN 37240. RP Levey, AS (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR HOSP,750 WASHINGTON ST,NEMCH 391,BOSTON,MA 02111, USA. NR 45 TC 74 Z9 75 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1996 VL 7 IS 12 BP 2616 EP 2626 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA VZ952 UT WOS:A1996VZ95200016 ER PT J AU Zhou, HB Weinberg, CR Wilcox, AJ Baird, DD AF Zhou, HB Weinberg, CR Wilcox, AJ Baird, DD TI A random-effects model for cycle viability in fertility studies SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE aggregated Bernoulli outcomes; beta distribution; EM algorithm; fertility; latent variables; random effect ID MAXIMUM-LIKELIHOOD-ESTIMATION; LONGITUDINAL DATA-ANALYSIS; PRENATAL EXPOSURE; EM ALGORITHM; PREGNANCY; CONCEPTION; OVULATION; SURVIVAL; FECUNDABILITY; TEMPERATURE AB Models for fertility that take into account the timing of intercourse relative to ovulation are needed to estimate the influence of both endogenous and exogenous factors on human fertility. The classical model assumes that some menstrual cycles are ''viable'' and some are not, where ''viability'' is determined by whether hormonal, uterine, and gamete-related factors are favorable to gestation. Within each viable cycle, the various days with intercourse are assumed to act independently; within each nonviable cycle, the days with intercourse can have no effect. Cycle viability for individual cycles is latent in that it is not ascertainable when conception does not occur. The classical model neglects the statistical dependency of outcomes among menstrual cycles within individual couples. Current marginal approaches cannot determine the degree to which heterogeneity in fecundability is biologically based versus the degree to which it is secondary to variation in intercourse behavior from couple to couple. We describe a random-effects model based on assuming that the cycle viability probability varies from couple to couple according to a beta distribution, and we use an EM algorithm to fit the model. The proposed estimating procedure is fully expandable to allow covariate effects on the beta variate. Our method can be applied more generally whenever dependency among Bernoulli trials is induced by a susceptibility state and the outcomes can be observed only in the aggregate. Based on data from a cohort of couples with no known fertility problems who were attempting pregnancy, cycle viability is found to be heterogeneous among couples. Stratification on the presence or absence of prenatal exposure of the woman to her mother's cigarette smoking revealed a statistically significant difference in the two cycle viability distributions. We discuss differences in the interpretation of the beta model compared to the marginal approach based on generalized estimating equations. C1 NIEHS,BIOSTAT BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Zhou, HB (reprint author), UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27599, USA. OI Baird, Donna/0000-0002-5544-2653 NR 32 TC 33 Z9 33 U1 0 U2 2 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1996 VL 91 IS 436 BP 1413 EP 1422 DI 10.2307/2291567 PG 10 WC Statistics & Probability SC Mathematics GA VX913 UT WOS:A1996VX91300004 ER PT J AU Bour, S Strebel, K AF Bour, S Strebel, K TI Human immunodeficiency virus (HIV) type 2 envelope protein is a functional complement to HIV type 1 Vpu that enhances particle release of heterologous retroviruses SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOPLASMIC DOMAIN; GLYCOPROTEIN PRECURSOR; ENDOPLASMIC-RETICULUM; PERSISTENT INFECTION; INDUCED DEGRADATION; CD4; CELLS; MATURATION; GENE; PHOSPHORYLATION AB We have recently shown that the envelope glycoprotein of the ROD10 isolate of human immunodeficiency virus type 2 (HIV-2) has the ability to positively regulate HIV-2 viral particle release, The activity provided by the ROD10 Env was remarkably similar to that of the HIV-1 Vpu protein, thus raising the possibility that the two proteins act in a related fashion, We now show that the ROD10 Env can functionally replace Vpu to enhance the rate of HIV-1 particle release. When provided in trans, both Vpu and the ROD10 Env restored wild-type levels of particle release in a Vpu-deficient mutant of the NL4-3 molecular clone with indistinguishable efficiencies. This effect was independent of the presence of the HIV-1 envelope protein. The ROD10 Env also enhanced HIV-1 particle release in the context of HIV-2 chimeric viruses containing the HIV-1 gag-pol, indicating a lack of need for additional HIV-1 products in this process, In addition, we show for the first time that HIV-1 Vpu, as well as ROD10 Env, has the ability to enhance simian immunodeficiency virus (SIV) particle release. The effects of Vpu and ROD10 Env on SIV particle release were indistinguishable and were observed in the context of full-length SIV mac239 and simian-human immunodeficiency virus chimeras, These results further demonstrate that ROD10 Env can functionally complement Vpu with respect to virus release, In contrast, we found no evidence of a destabilizing activity of ROD10 Env on the CD4 molecule, HIV-1 and HIV-2 thus appear to have evolved genetically distinct but functionally similar strategies to resolve the common problem of efficient release of progeny virus from infected cells. RP Bour, S (reprint author), NIAID,NIH,MOL MICROBIOL LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 312,BETHESDA,MD 20892, USA. NR 49 TC 80 Z9 81 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 DEC PY 1996 VL 70 IS 12 BP 8285 EP 8300 PG 16 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400005 PM 8970948 ER PT J AU Karupiah, G Buller, RML vanRooijen, N Duarte, CJ Chen, JH AF Karupiah, G Buller, RML vanRooijen, N Duarte, CJ Chen, JH TI Different roles for CD4(+) and CD8(+) T lymphocytes and macrophage subsets in the control of a generalized virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA VIRUS; ECTROMELIA VIRUS; INTERFERON-GAMMA; DEFICIENT MICE; CELL RESPONSES; ANTIGEN PRESENTATION; VIRAL-INFECTION; INFLUENZA; DEPLETION; INVIVO AB The importance of T-lymphocyte subsets in the control of poxvirus infections is controversial, To determine the relative contribution of lymphocyte subsets important for recovery from infection with ectromelia virus (EV), a natural murine poxvirus pathogen, C57BL/6 (B6) mice lacking functional CD8(+) T cells because of disruption of the beta 2-microglobulin gene or lacking functional CD4(+) T cells because of disruption of the I-A(beta) gene, acutely depleted of CD8(+) or CD4(+) T cells with monoclonal antibody, or depleted of macrophage subsets by the macrophage suicide technique were used, Recovery from infection was strictly dependent on the effector functions of CD8(+) T cells, in the absence of which 100% mortality resulted, This lymphocyte population had demonstrable antiviral activity early in the infection process even before class I major histocompatibility complex (MHC)-restricted CD8(+) cytotoxic T-lymphocyte (CTL) activity was detectable, CD4(+) T cells were found to be necessary for the generation of an optimal virus-specific, class I MHC-restricted CD8(+) CTL response and contributed to virus clearance not involving cytolytic mechanisms, In both models of CD4(+) T-cell deficiency, virus clearance was incomplete and persisted at low levels in most organs and at very high levels in the skin, but the animals did not die, The elimination of macrophage subpopulations impeded virus clearance, impaired the generation of class I MHC-restricted antiviral CTL response, and resulted in 100% mortality, These findings establish an absolute requirement for CD8(+) and CD4(+) T lymphocytes and macrophage subsets in the elimination of a natural murine poxvirus infection and support the idea that macrophages may be essential accessory cells for the generation of class I MHC-restricted antiviral CTL responses. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. FREE UNIV AMSTERDAM,FAC MED,DEPT CELL BIOL & IMMUNOL,AMSTERDAM,NETHERLANDS. RP Karupiah, G (reprint author), AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,DIV CELL BIOL & IMMUNOL,CANBERRA,ACT 2601,AUSTRALIA. RI Karupiah, Gunasegaran/J-4707-2013 NR 57 TC 128 Z9 128 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 DEC PY 1996 VL 70 IS 12 BP 8301 EP 8309 PG 9 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400006 PM 8970949 ER PT J AU Watkins, BA Buge, S Aldrich, K Davis, AE Robinson, J Reitz, MS RobertGuroff, M AF Watkins, BA Buge, S Aldrich, K Davis, AE Robinson, J Reitz, MS RobertGuroff, M TI Resistance of human immunodeficiency virus type 1 to neutralization by natural antisera occurs through single amino acid substitutions that cause changes in antibody binding at multiple sites SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; GP120 SURFACE GLYCOPROTEIN; POINT MUTATION; ENVELOPE GLYCOPROTEIN; SYNTHETIC PEPTIDES; FUNCTIONAL INTERACTION; TRANSMEMBRANE PROTEIN; HTLV-III; HIV-1; EPITOPE AB The ability of human immunodeficiency virus type 1 (HIV-1) to replicate in the presence of strong immune responses to the virus may be due to its high mutation rate, which provides envelope gene variability for selection of neutralization-resistant variants. Understanding neutralization escape mechanisms is therefore important for the design of HIV-1 vaccines and our understanding of the disease process, In this report, we analyze mutations at amino acid positions 281 and 582 in the HIV-1 envelope, where substitutions confer resistance to broadly reactive neutralizing antisera from seropositive individuals, Neither of these mutations lies within an antibody-binding site, and therefore the mechanism of immune escape in both cases is by alteration of the shape of the envelope proteins. The conformation of the CD4-binding site is shown to be critical with regard to presentation of other discontinuous epitopes. From our analysis of the neutralization of these variants, we conclude that escape from polyclonal sera occurs through alterations at several different epitopes, generally resulting from single amino acid substitutions which influence envelope conformation. Experiments on a double mutant showed that the combination of both mutations is not additive, suggesting that these variants utilized alternate pathways to elicit similar alterations of the HIV-1 envelope structure. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH SCI,DEPT PEDIAT,FARMINGTON,CT 06030. NR 54 TC 55 Z9 56 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 DEC PY 1996 VL 70 IS 12 BP 8431 EP 8437 PG 7 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400021 PM 8970964 ER PT J AU Masuda, M Masuda, M Hanson, CA Hoffman, PM Ruscetti, SK AF Masuda, M Masuda, M Hanson, CA Hoffman, PM Ruscetti, SK TI Analysis of the unique hamster cell tropism of ecotropic murine leukemia virus PVC-211 SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID TRANSPORTER; N-LINKED GLYCOSYLATION; COMPLETE NUCLEOTIDE-SEQUENCE; RECEPTOR-BINDING DOMAIN; RETROVIRUS RECEPTOR; MUTATIONAL ANALYSIS; HOST-RANGE; NEUROPATHOGENIC VARIANT; ENVELOPE PROTEIN; GENE AB PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV). Previous studies from our laboratory demonstrated that unlike the parental F-MuLV, PVC-211 MuLV can infect rat brain capillary endothelial cells efficiently and that it has acquired genetic changes responsible for its expanded cellular tropism. To determine if PVC-211 MuLV also has expanded its host range, we tested its infectivity on Chinese hamster ovary-derived CHO-k1 cells, which are generally resistant to ecotropic MuLV, The results indicated that PVC-211 MuLV, but not F-MuLV, mas highly infectious for CHO-K1 cells. Studies using glycosylation inhibitors and glycosylation mutants of CHO-K1 cells, as well as interference studies, suggested that PVC-211 MuLV has acquired the ability to interact with the ecotropic MuLV receptor on CHO-K1 cells that has undergone glycosylation-dependent modification. Using chimeric viruses between PVC-211 MuLV and F-MuLV, we were able to localize the viral genetic element crucial for CHO-K1 cell tropism within the env gene of PVC-211 MuLV and show that glycine at position 116 and lysine at position 129 of the envelope glycoprotein SU were important. These viral determinants also appear to confer tropism for other hamster cells resistant to ordinary ecotropic MuLVs. Further studies on the interaction between PVC-211 MuLV and the receptor on hamster cells may provide novel insights into the molecular mechanisms for receptor recognition and binding bg viral envelope glycoproteins. C1 NCI, FREDERICK CANC RES & DEV CTR, MOL ONCOL LAB, FREDERICK, MD 21702 USA. SCI APPLICAT INT CORP, LAB CELLULAR BIOCHEM, FREDERICK, MD 21702 USA. UNIV MARYLAND, BALTIMORE, MD 21201 USA. DEPT VET AFFAIRS MED CTR, RES SERV, BALTIMORE, MD 21201 USA. NR 53 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1996 VL 70 IS 12 BP 8534 EP 8539 PG 6 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400034 PM 8970977 ER PT J AU Muralidhar, S Doniger, J Mendelson, E Araujo, JC Kashanchi, F Azumi, N Brady, JN Rosenthal, LJ AF Muralidhar, S Doniger, J Mendelson, E Araujo, JC Kashanchi, F Azumi, N Brady, JN Rosenthal, LJ TI Human cytomegalovirus mtrII oncoprotein binds to p53 and down-regulates p53-activated transcription SO JOURNAL OF VIROLOGY LA English DT Article ID WILD-TYPE P53; CELLULAR TUMOR-ANTIGEN; HUMAN PAPILLOMAVIRUS TYPE-16; RETINOBLASTOMA GENE-PRODUCT; CYCLE CHECKPOINT PATHWAY; TRANSFORMING REGION-II; ACTIVATION DOMAIN; MALIGNANT TRANSFORMATION; SEQUENCE-ANALYSIS; E6 PROTEINS AB The 79-amino-acid (79-aa) open reading frame (UL111a) gene within morphological transforming region II (mtrII) of human cytomegalovirus strain Towne has been shown to transform rodent cells in vitro (J. Thompson, J. Doniger, and L. J. Rosenthal, Arch. Virol. 136:161-172, 1994). Moreover, a translation termination linker (TTL) mutant of mtrII that coded for the first 49 aa of mtrII oncoprotein (designated TTL(49)) was sufficient for malignant transformation, whereas a TTL mutant that coded for the first 24 aa (designated TTL(24)) was not. The current study demonstrates the binding of mtrII oncoprotein to the tumor suppressor protein p53 both in vivo using transiently transfected cells and in vitro using labeled proteins, Furthermore, the C-terminally truncated mtrII protein TTL(49), but not truncated protein TTL(24), bound to p53. The mtrII binding domain mapped to the N-terminal region of p53, residues 1 to 106, with a critical region from aa 27 to 44, whereas the p53 binding domain of mtrII protein was the first 49 aa, Furthermore, mtrII inhibited p53-activated transcription, indicating its ability to alter p53-directed cellular regulatory mechanisms, mtrII oncoprotein was detected both in stably transfected NIH 3T3 cell lines and human cytomegalovirus-infected HEL 299 cells (as early as 12 h after infection) in the perinuclear region and in the nucleus, mtrII-transformed cell lines, at both early and late passage, exhibited high levels of p53 with a 15-fold-extended half-life, However, p53-activated transcription was suppressed in these cells in spite of the increased p53 levels, Finally, the results with wild-type mtrII and its TTL mutants with respect to p53 binding, p53-activated transcription, and transforming ability suggest that the mechanism of mtrII transformation is linked to both p53 binding and disruption of p53 cell regulation. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NCI,MOL VIROL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 37259-07] NR 72 TC 40 Z9 41 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 DEC PY 1996 VL 70 IS 12 BP 8691 EP 8700 PG 10 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400053 PM 8970996 ER PT J AU Lynch, WP Snyder, EY Qualtiere, L Portis, JL Sharpe, AH AF Lynch, WP Snyder, EY Qualtiere, L Portis, JL Sharpe, AH TI Late virus replication events in microglia are required for neurovirulent retrovirus-induced spongiform neurodegeneration: Evidence from neural progenitor-derived chimeric mouse brains SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; CENTRAL-NERVOUS-SYSTEM; IMMUNE-DEFICIENCY SYNDROME; ECOTROPIC RETROVIRUS; ENVELOPE PROTEIN; CELL-LINES; NEUROTROPIC RETROVIRUS; INCUBATION PERIOD; SLOW DISEASE; INFECTION AB CasBrE is a neurovirulent murine retrovirus which induces a spongiform myeloencephalopathy in susceptible mice. Genetic mapping studies have indicated that sequences responsible For neurovirulence reside within the env gene. To address the question of direct envelope protein neurotoxicity in the central nervous system (CNS), we have generated chimeric mice expressing the CasBrE envelope protein in cells of neuroectodermal origin, Specifically, the multipotent neural progenitor cell line C17.2 was engineered to express the CasBrE env gene as either gp70/p15E (Cas(E)) or gp70 alone (Cas(ES)). Cas(E) expression in these cells resulted in complete (>10(5)) interference of superinfection with Friend murine leukemia virus clone FB29, whereas Cas(ES) expression resulted in a 1.8-log-unit decrease in FB29 titer. Introduction of these envelope-expressing C17.2 cells into the brains of highly susceptible IRW mice resulted in significant engraftment as integral cytoarchitecturally correct components of the CNS. Despite high-level envelope protein expression from the engrafted cells, no evidence of spongiform neurodegeneration was observed. To examine whether early virus replication events were necessary for pathogenesis, C17.2 cells expressing whole virus were transplanted into mice in which virus replication in the host was specifically restricted by FV-1 to preintegration events. Again, significant C17.2 cell engraftment and infectious virus expression failed to precipitate spongiform lesions. Ln contrast, transplantation of virus-expressing C17.2 progenitor cells in the absence of the Fv-1 restriction resulted in extensive spongiform neurodegeneration by 2 weeks postengraftment. Cytological examination indicated that infection had spread beyond the engrafted cells, and in particular to host microglia. Spongiform neuropathology in these animals was directly correlated with CasBrE env expression in microglia rather than expression from neural progenitor cells. These results suggest that the envelope protein of CasBrE is not itself neurotoxic but that virus infectious events beyond binding and fusion in microglia are necessary for the induction of CNS disease. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL & PEDIAT,BOSTON,MA 02115. UNIV SASKATCHEWAN,DEPT MICROBIOL,SASKATOON,SK S7N 0W0,CANADA. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RP Lynch, WP (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,LMRC 514,221 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NINDS NIH HHS [R01 NS31065] NR 63 TC 32 Z9 32 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 DEC PY 1996 VL 70 IS 12 BP 8896 EP 8907 PG 12 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400076 PM 8971019 ER PT J AU Chesebro, B Wehrly, K Nishio, J Perryman, S AF Chesebro, B Wehrly, K Nishio, J Perryman, S TI Mapping of independent V3 envelope determinants of human immunodeficiency virus type 1 macrophage tropism and syncytium formation in lymphocytes SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-LINE; INFECTIOUS MOLECULAR CLONE; FOCUS-INDUCING VIRUS; BIOLOGICAL PHENOTYPE; HIV-1; GP120; LOOP; SEQUENCES; AIDS; IDENTIFICATION AB The V3 region of the human immunodeficiency virus type 1 (HIV-1) envelope protein is known to have a major influence on macrophage tropism as well as the ability to cause syncytium formation or fusion in CD4-positive lymphocyte cultures. Using infectious molecular HIV-1 clones, a series of mutant clones was created which allowed detailed mapping of V3 amino acid positions involved in these properties. In these experiments the non-syncytium-inducing phenotype in T cells did not always correlate with macrophage tropism. Macrophage tropism appeared to depend on the presence of certain combinations of amino acids at five specific positions within and just outside of the V3 loop itself, whereas syncytium formation in lymphocytes was influenced by substitution of particular residues at two to four positions within V3. In most cases, different V3 amino acid positions were found to independently influence macrophage tropism and syncytium formation in T cells and position 13 was the only V3 location which appeared to simultaneously influence both macrophage tropism and syncytium formation in lymphocytes. RP Chesebro, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 50 TC 125 Z9 128 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 DEC PY 1996 VL 70 IS 12 BP 9055 EP 9059 PG 5 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400100 PM 8971043 ER PT J AU Wonderling, RS Owens, RA AF Wonderling, RS Owens, RA TI The Rep68 protein of adeno-associated virus type 2 stimulates expression of the platelet-derived growth factor B c-sis proto-oncogene (vol 70, pg 4784, 1996) SO JOURNAL OF VIROLOGY LA English DT Correction, Addition RP Wonderling, RS (reprint author), NIDDKD,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892, USA. NR 1 TC 2 Z9 2 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 DEC PY 1996 VL 70 IS 12 BP 9084 EP 9084 PG 1 WC Virology SC Virology GA VT704 UT WOS:A1996VT70400107 ER PT J AU Burg, MB Kwon, ED Peters, EM AF Burg, MB Kwon, ED Peters, EM TI Glycerophosphocholine and betaine counteract the effect of urea on pyruvate kinase SO KIDNEY INTERNATIONAL LA English DT Article ID MEDULLARY ORGANIC OSMOLYTES; ENZYME-ACTIVITY; CELLS; RAT; PROTEIN; SOLUTES; TRANSPORT; TAURINE AB Renal medullary cells contain large quantities of organic osmolytes when the levels of salt and urea in renal medullary interstitial fluid are high. Two of these osmolytes, betaine and glycerophosphocholine (GPC), are methylamines. Methylamines generally counteract the perturbing effects of urea on enzymes and other macromolecules. Betaine was previously shown to counteract the effect of urea on enzymes in vitro and to protect renal cells in tissue culture from harmful effects of high urea. Nevertheless, renal medullary cells in vivo and in tissue culture specifically accumulate GPC rather than betaine, in response to high urea. In the present studies we tested directly whether GPC counteracts the effect of urea on the K-m of pyruvate kinase (PK) for ADP and compared the effectiveness in the regard of GPC to that of betaine. We find the urea increases the K-m (as previously observed), that betaine and GPC decrease it, and that the increase caused by urea is counteracted by betaine or by GPC. The effects of GPC are slightly less than those of betaine. In addition, other renal medullary organic osmolytes (namely sorbitol, inositol and taurine) were already known to be compatible osmolytes whose accumulation protects renal medullary cells from hypertonicity because they have little effect on enzyme function. In agreement with this generalization we find that high sorbitol or inositol has little or no effect on PK activity, but surprisingly that taurine reduces V-max and greatly elevates K-m. In conclusion, the main finding is direct evidence that GPC is a counteracting osmolyte, which explains its accumulation in response to high urea. However, we do not find that GPC is a more effective counteracting osmolyte than betaine, which leaves unexplained the preference of renal cells for GPC over betaine for counteracting the perturbing effect of urea. RP Burg, MB (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 25 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1996 VL 50 SU 57 BP S100 EP S104 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA VW139 UT WOS:A1996VW13900019 ER PT J AU Hixon, ML Lewis, AM Levine, AS Chattopadhyay, SK AF Hixon, ML Lewis, AM Levine, AS Chattopadhyay, SK TI Limited diversity in the major histocompatibility complex class II Loci of Syrian hamster DNA SO LABORATORY ANIMAL SCIENCE LA English DT Article ID GENE; BETA C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. NR 15 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1996 VL 46 IS 6 BP 679 EP 681 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA WC741 UT WOS:A1996WC74100014 PM 9001183 ER PT J AU Jacot, TA Striker, GE StetlerStevenson, MA Striker, LJ AF Jacot, TA Striker, GE StetlerStevenson, MA Striker, LJ TI Mesangial cells from transgenic mice with progressive glomerulosclerosis exhibit stable, phenotypic changes including undetectable MMP-9 and increased type IV collagen SO LABORATORY INVESTIGATION LA English DT Article ID GROWTH-FACTOR-I; MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; COMPETITIVE PCR; MESSENGER-RNA; FACTOR-BETA; HORMONE; GLOMERULI; RAT AB Mice transgenic for bovine growth hormone (bGH) develop progressive mesangial sclerosis resulting in uremia. Mesangial cells from bGH mice were isolated to determine whether the cells maintained a stable phenotypic change in the synthesis and degradation of extracellular matrix, which contribute to the glomerular lesions in vivo. The bGH mesangial cells were 1.2-fold larger than cells from control mice. They had a 1.7-fold increase in doubling time, a 7-fold decrease in labeling index (p < 0.0001), and a 2.4- and 2-fold decrease in c-myc (p < 0.05) and insulin-like growth factor I gene expression, respectively. Collagen synthesis and degradation were studied by PCR, ELISA, and gelatin zymography. bGH mesangial cell a, collagen IV mRNA levels were increased 2.3-fold (0.47 +/- 0.25 versus 0.20 +/- 0.09 attomoles/500 cells, p < 0.01) whereas secreted collagen IV and collagen IV in the cell lysates were increased 1.4-fold (25.1 +/- 5 versus 17.2 +/- 4 ng/ml/10(5) cells) and 1.8-fold (30.5 +/- 3 versus 16.7 +/- 3 ng/ml/10(5), p < 0.05), respectively. There were no differences in collagen I mRNA levels or in the protein content of either the media or cell lysates. We were not able to detect metalloproteinase 9 (MMP-9) mRNA expression or MMP-9 protein in bGH mesangial cell medium, whereas both mRNA and protein were present in controls. MMP-2 mRNA and enzyme activity in bGH cells were, however, elevated 1.5-fold (p < 0.05) and 2.1-fold (p = 0.05) over controls. Transforming growth factor pi mRNA in bGH cells was 1.6-fold higher than that of controls (p < 0.05). The data suggest that (a) mesangial lesions may result from stable, genetically induced, phenotypic changes in mesangial cells, and (b) alterations of MMP-9 and collagen IV expression by mesangial cells may contribute to an imbalance between extracellular matrix synthesis and degradation and play a critical role in the genesis of glomerulosclerosis. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 42 TC 61 Z9 62 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1996 VL 75 IS 6 BP 791 EP 799 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA VY754 UT WOS:A1996VY75400004 PM 8973474 ER PT J AU Gronenborn, AM AF Gronenborn, AM TI Guest editor's foreword SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Editorial Material RP Gronenborn, AM (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD DEC PY 1996 VL 34 SI SI BP S1 EP S1 PG 1 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA WK909 UT WOS:A1996WK90900001 ER PT J AU Pierpaoli, C Basser, PJ AF Pierpaoli, C Basser, PJ TI Toward a quantitative assessment of diffusion anisotropy SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; anisotropy; diffusion; tensor ID MYELIN FIBER ORIENTATION; WATER DIFFUSION; MAGNETIC-RESONANCE; WHITE-MATTER; WEIGHTED MR; HUMAN BRAIN; ANALYTICAL EXPRESSIONS; RESTRICTED DIFFUSION; NERVOUS-SYSTEM; SPIN-ECHO AB Indices of diffusion anisotropy calculated from diffusion coefficients acquired in two or three perpendicular directions are rotationally variant. In living monkey brain, these indices severely underestimate the degree of diffusion anisotropy. New indices calculated from the entire diffusion tensor are rotationally invariant (RI). They show that anisotropy is highly variable in different white matter regions depending on the degree of coherence of fiber tract directions. In structures with a regular, parallel fiber arrangement, water diffusivity in the direction parallel to the fibers (D-parallel to approximate to 1400-1800 x 10(-6) mm(2)/s) is almost 10 times higher than the average diffusivity in directions perpendicular to them ((D + D perpendicular to')/2 approximate to 150-300 x 10(-6) mm(2)/s), and is almost three times higher than previously reported. In structures where the fiber pattern is less coherent (e.g., where fiber bundles merge), diffusion anisotropy is significantly reduced. However, RI anisotropy indices are still susceptible to noise contamination. Monte Carlo simulations show that these indices are statistically biased, particularly those requiring sorting of the eigenvalues of the diffusion tensor based on their magnitude. A new intervoxel anisotropy index is proposed that locally averages inner products between diffusion tensors in neighboring voxels. This ''lattice'' RI index has an acceptably low error variance and is less susceptible to bias than any other RI anisotropy index proposed to date. C1 NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD. RP Pierpaoli, C (reprint author), NINCDS,NB,NIH,BLDG 10,ROOM 1C227,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 NR 40 TC 1468 Z9 1491 U1 3 U2 43 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1996 VL 36 IS 6 BP 893 EP 906 DI 10.1002/mrm.1910360612 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU890 UT WOS:A1996VU89000011 PM 8946355 ER PT J AU vanDusschoten, D Moonen, CTW deJager, PA VanAs, H AF vanDusschoten, D Moonen, CTW deJager, PA VanAs, H TI Unraveling diffusion constants in biological tissue by combining Carr-Purcell-Meiboom-Gill imaging and pulsed field gradient NMR SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE PFG NMR; CPMG imaging; diffusion ID NUCLEAR MAGNETIC-RESONANCE; RELAXATION-TIMES; T2; BRAIN; DISTRIBUTIONS; INFORMATION; STROKE; WATER AB A diffusion-weighted multi-spin-echo pulse sequence is presented, which allows for simultaneous measurement of T-2, the fractional amplitude, and the diffusion constant of different fractions. Monte Carlo simulations demonstrate an improvement of this sequence with respect to the accuracy of diffusion constant and fractional amplitude for slow exchange. Examples are shown for a simple phantom containing two fractions. In addition, experiments on cat brain in healthy condition and following occlusion of the middle cerebral artery show that the fractional amplitude and the diffusion constant of cerebral spinal fluid and normal brain tissue can be analyzed within each pixel with acceptable accuracy. C1 AGR UNIV WAGENINGEN,DEPT MOL PHYS,NL-6703 HA WAGENINGEN,NETHERLANDS. NCRR,NIH,BETHESDA,MD. RI Van As, Henk/A-2787-2013; Moonen, Chrit/K-4434-2016 OI Van As, Henk/0000-0003-1076-391X; Moonen, Chrit/0000-0001-5593-3121 NR 28 TC 56 Z9 57 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1996 VL 36 IS 6 BP 907 EP 913 DI 10.1002/mrm.1910360613 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU890 UT WOS:A1996VU89000012 PM 8946356 ER PT J AU Brown, DR Brousseau, ME Shamburek, RD Talley, GD Meyn, S Demosky, SJ SantamarinaFojo, S Brewer, HB Hoeg, JM AF Brown, DR Brousseau, ME Shamburek, RD Talley, GD Meyn, S Demosky, SJ SantamarinaFojo, S Brewer, HB Hoeg, JM TI Adenoviral delivery of low-density lipoprotein receptors to hyperlipidemic rabbits: Receptor expression modulates high-density lipoproteins SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID APOLIPOPROTEIN-A-I; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; CORONARY HEART-DISEASE; ESTER TRANSFER PROTEIN; CELL-DERIVED CHOLESTEROL; PRIMARY-PREVENTION TRIAL; PRE-BETA; WHHL-RABBIT; RECOMBINANT ADENOVIRUSES; ANIMAL-MODEL AB Plasma concentrations of low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs) are inversely related in several dyslipoproteinemias. To elucidate the interactions between these lipoproteins, we used a recombinant adenovirus (hLDLR-rAdV) to express human LDL receptors (hLDLRs) in LDL receptor-deficient rabbits. hLDLR-rAdV administration resulted in hepatocyte expression and a reduction of total, intermediate density lipoprotein (IDL), and LDL cholesterol. In addition, we found that hLDLR-rAdV treatment induced (1) increased very-low-density lipoprotein (VLDL) cholesterol, (2) increased VLDL, IDL and LDL triglycerides, (3) decreased alpha- and pre-beta-migrating apolipoprotein E (apo E) and decreased pre-beta-migrating apo A-I at 2 to 4 days posttreatment, and (4) increased total plasma apo A-I and pre-beta-migrating apo A-I beginning 8 to 10 days posttreatment. Virtually all plasma apo A-I was present on alpha- and pre-beta-HDL. Pre-beta-HDL particles with size and electrophoretic properties consistent with nascent HDL demonstrated the greatest relative apo A-I enrichment following hLDLR-rAdV treatment. In summary, enhanced expression of hepatocyte LDLRs by hLDLR-rAdV treatment markedly altered apo A-I-containing lipoproteins and IDL and LDL. The use of recombinant viruses to express physiologically relevant genes in intact animals, analogous to transfection of cells in culture, provides a new strategy for the evaluation of effects of specific gene products on metabolic systems in vivo. Copyright (C) 1996 by W.B. Saunders Company C1 NHLBI,NIH,MOL DIS BRANCH,BETHESDA,MD 20892. NR 92 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 1996 VL 45 IS 12 BP 1447 EP 1457 DI 10.1016/S0026-0495(96)90172-9 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VX694 UT WOS:A1996VX69400002 PM 8969276 ER PT J AU Gorospe, M Wang, XT Guyton, KZ Holbrook, NJ AF Gorospe, M Wang, XT Guyton, KZ Holbrook, NJ TI Protective role of p21(Waf1/Cip1) against prostaglandin A(2)-mediated apoptosis of human colorectal carcinoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID P53-INDEPENDENT PATHWAY; GROWTH ARREST; G1 CHECKPOINT; DNA-DAMAGE; EXPRESSION; WAF1/CIP1; CYCLE; PROTEIN; KINASES; STRESS AB Prostaglandin A(2) (PGA(2)) suppresses tumor growth in vivo, is potently antiproliferative in vitro, and is a model drug for the study of the mammalian stress response. Our previous studies using breast carcinoma MCF-7 cells suggested that p21(Waf1/Cip1) induction enabled cells to survive PGA(2) exposure. Indeed, the marked sensitivity of human colorectal carcinoma RKO cells to the cytotoxicity of PGA(2) is known to be associated with a lack of a PGA(2)-mediated increase in p21(Waf1/Cip1) expression, inhibition of cyclin-dependent kinase activity, and growth arrest. To determine if cell death following exposure to PGA(2) could be prevented by forcing the expression of p21(Waf1/Cip1) in RKO cells, we utilized an adenoviral vector-based expression system. We demonstrate that ectopic expression of p21(Waf1/Cip1) largely rescued RKO cells from PGA(2)-induced apoptotic cell death, directly implicating p21(Waf1/Cip1) as a determinant of the cellular outcome (survival versus death) following exposure to PGA(2). To discern whether p21(Waf1/Cip1)-mediated protection operates through the implementation of cellular growth arrest, other growth-inhibitory treatments were studied for the ability to attenuate PGA(2)-induced cell death. Neither serum depletion nor suramin (a growth factor receptor antagonist) protected RKO cells against PGA(2) cytotoxicity, and neither induced p21(Waf1/Cip1) expression. Mimosine, however, enhanced p21(Waf1/Cip1) expression, completely inhibited RKO cell proliferation, and exerted marked protection against a subsequent PGA(2) challenge. Taken together, our results directly demonstrate a protective role for p21(Waf1/Cip1) during PGA(2) cellular stress and provide strong evidence that the implementation of cellular growth arrest contributes to this protective influence. C1 NIA,CELLULAR & MOL BIOL LAB,NIH,BALTIMORE,MD 21224. NR 36 TC 149 Z9 153 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 DEC PY 1996 VL 16 IS 12 BP 6654 EP 6660 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800005 PM 8943319 ER PT J AU Ludwig, S Engel, K Hoffmeyer, A Sithanandam, G Neufeld, B Palm, D Gaestel, M Rapp, UR AF Ludwig, S Engel, K Hoffmeyer, A Sithanandam, G Neufeld, B Palm, D Gaestel, M Rapp, UR TI 3pK, a novel mitogen-activated protein (MAP) kinase-activated protein kinase, is targeted by three MAP kinase pathways SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; HEAT-SHOCK PROTEINS; C-JUN; PHOSPHORYLATION SITES; RAF-1 KINASE; MYOCYTE HYPERTROPHY; S6 KINASE; IN-VITRO; V-RAF; STRESS AB Recently we have identified a mitogen-activated protein kinase (MAPK)-activated protein kinase, named 3pK (G. Sithanandam, F. Latif, U. Smola, R. A. Bernal, F.-M. Duh, H. Li, I. Kuzmin, V. Wirier, L. Geil, S. Shresta, P. A. Lloyd, S. Bader, Y. Sekido, K. D. Tartof, V. I. Kashuba, E. R. Zabarovsky, M. Dean, G. Klein, B. Zbar, M. I. Lerman, J. D. Minna, U. R. Rapp, and A. Allikmets, Mel. Cell. Biol. 16:868-876, 1996). In vitro characterization of the kinase revealed that 3pK is activated by ERK. It was further shown that 3pK is phosphorylated in vivo after stimulation of cells with serum. However, the in vivo relevance of this observation in terms of involvement of the Raf/MEK/ERK cascade has not been established. Here we show that 3pK is activated in vivo by the growth inducers serum and tetradecanoyl phorbol acetate in promyelocytic HL60 cells and transiently transfected embryonic kidney 293 cells. Activation of 3pK was Raf dependent and was mediated by the Raf/MEK/ERK kinase cascade. 3pK was also shown to be activated after stress stimulation of cells. In vitro studies with recombinant proteins demonstrate that in addition to ERK, members of other subgroups of the MARK family, namely, p38RK and Jun-N-terminal kinases/stress-activated protein kinases, were also able to phosphorylate and activate 3pK. Cotransfection experiments as well as the use of a specific inhibitor of p38RK showed that these in vitro upstream activators also function In vivo, identifying 3pK as the first kinase to be activated through all three MAPK cascades. Thus, 3pK is a novel convergence point of different MAPK pathways and could function as an integrative element of signaling in both mitogen and stress responses. C1 MAX DELBRUCK CTR MOL MED,D-13122 BERLIN,GERMANY. UNIV WURZBURG,BIOZENTRUM,INST PHYSIOL CHEM 1,D-97074 WURZBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Ludwig, S (reprint author), INST MED STRAHLENKUNDE & ZELLFORSCH,VERBASCHERSTR 5,D-97078 WURZBURG,GERMANY. OI Gaestel, Matthias/0000-0002-4944-4652; Ludwig, Stephan/0000-0003-4490-3052 NR 62 TC 150 Z9 151 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 DEC PY 1996 VL 16 IS 12 BP 6687 EP 6697 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800009 PM 8943323 ER PT J AU Orosz, A Wisniewski, J Wu, C AF Orosz, A Wisniewski, J Wu, C TI Regulation of Drosophila heat shock factor trimerization: Global sequence requirements and independence of nuclear localization SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION DOMAIN; DNA-BINDING ACTIVITY; COILED-COIL; GENE-TRANSCRIPTION; MOLECULAR-CLONING; FACTOR CONTAINS; HSP70 GENE; YEAST; PROTEIN; PROMOTER AB Heat shock transcription factor (HSF) is a multidomain protein that exists as a monomer under normal conditions and is reversibly induced upon heat shock to a trimeric state that binds to DNA with high affinity, The maintenance of the monomeric state is dependent on hydrophobic heptad repeats located at the amino-and and carboxy-terminal regions which have been proposed to form an intramolecular coiled-coil structure. In a systematic deletion analysis to identify other regions of HSF that may be required to regulate its oligomeric state, we have found that local sequences encompassing the carboxy-terminal end of the DNA binding domain and a broad region of HSF between the heptad repeats also contribute to this regulation. Immunocytochemical analysis of mutant HSF proteins revealed a canonical motif required for nuclear localization, HSF proteins lacking the nuclear localization signal remain in the cytoplasm, but these HSFs nonetheless exhibit reversible heat stress-inducible trimerization. The results indicate that the signals that regulate HSF trimerization operate in both the nuclear and cytoplasmic compartments of the cell. C1 NCI,MOL CELL BIOL LAB,BETHESDA,MD 20892. NR 65 TC 62 Z9 64 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1996 VL 16 IS 12 BP 7018 EP 7030 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800043 PM 8943357 ER PT J AU Sulciner, DJ Irani, K Yu, ZX Ferrans, VJ GoldschmidtClermont, P Finkel, T AF Sulciner, DJ Irani, K Yu, ZX Ferrans, VJ GoldschmidtClermont, P Finkel, T TI rac1 regulates a cytokine-stimulated, redox-dependent pathway necessary for NF-kappa B activation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTP-BINDING PROTEINS; TRANSCRIPTION FACTOR; NADPH OXIDASE; SIGNAL-TRANSDUCTION; ADENOVIRUS TYPE-5; HYDROGEN-PEROXIDE; HUMAN-FIBROBLASTS; OXIDATIVE STRESS; GENE-EXPRESSION; FREE-RADICALS AB The signal transduction pathway leading to the activation of the transcription factor NF-kappa B remains incompletely characterized. We demonstrate that in HeLa cells, transient expression of a constitutively active mutant of the small GTP-binding protein rad (V12rac1) leads to a significant increase in NF-kappa B transcriptional activity, In addition, expression of a dominant-negative rad mutant (N17rac1) inhibits basal and interleukin 1 beta-stimulated NF-kappa B activity. Gel shift analysis using nuclear extract prepared from HeLa cells infected with a recombinant adenovirus encoding N17rac1 (Ad.N17rac1) showed reduced levels of cytokine-stimulated DNA binding to a consensus NF-kappa B binding site. We demonstrate that rac proteins function downstream of ras proteins in the activation of NF-kappa B. In addition, V12rac1 stimulation of NF-kappa B activity is shown to be independent of the ability of rac proteins to activate the family of c-jun amino-terminal kinases, In an effort to further explore how rac proteins might regulate NF-kappa B activity, we demonstrate that expression of V12rac1 in HeLa cells or stimulation with cytokine results in a significant increase in intracellular reactive oxygen species (ROS). Treatment of cells with either of two chemically unrelated antioxidants inhibits the rise in ROS that occurs following V12rac1 expression as well as the ability of V12rac1 to stimulate NF-kappa B activity. These results suggest that in HeLa cells, rad regulates intracellular ROS production and that rac proteins function as part of a redox-dependent signal transduction pathway leading to NF-kappa activation. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21205. NR 50 TC 270 Z9 279 U1 0 U2 6 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 DEC PY 1996 VL 16 IS 12 BP 7115 EP 7121 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800053 PM 8943367 ER PT J AU Hajra, A Liu, PP Speck, NA Collins, FS AF Hajra, A Liu, PP Speck, NA Collins, FS TI Overexpression of core-binding factor or (CBF alpha) reverses cellular transformation by the CBF beta-smooth muscle myosin heavy chain chimeric oncoprotein (vol 15, pg 4980, 1996) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition C1 UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. DARTMOUTH COLL,SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. RP Hajra, A (reprint author), NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892, USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 1 TC 0 Z9 0 U1 0 U2 2 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 DEC PY 1996 VL 16 IS 12 BP 7185 EP 7185 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VU688 UT WOS:A1996VU68800061 PM 9333713 ER PT J AU Hager, GL Htun, H Barsony, J Fragoso, G Smith, C AF Hager, GL Htun, H Barsony, J Fragoso, G Smith, C TI Steroid receptor transactivation and the intranuclear architecture of target genes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOL VIROL LAB,BETHESDA,MD 20892. NIDDK,LAB CELL BIOCHEM & BIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 9 EP 9 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800008 ER PT J AU Smith, GH Kordon, EC AF Smith, GH Kordon, EC TI Evidence for a pluripotent mammary epithelial stem cell capable of self-renewal. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 37 EP 37 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800039 ER PT J AU Xie, H Notkins, AL Lan, MS AF Xie, H Notkins, AL Lan, MS TI Expression and molecular processing of a protein tyrosine phosphatase-like islet autoantigen, IA-2, in Sf 9 insect cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 81 EP 81 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800082 ER PT J AU Barsony, J Carroll, J Gould, DL McKoy, W Htun, H Hager, GL AF Barsony, J Carroll, J Gould, DL McKoy, W Htun, H Hager, GL TI Visualization of glucocorticoid receptor translocation and intranuclear movement in living cells with a green fluorescent protein chimera. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM,BETHESDA,MD 20892. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 85 EP 85 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800087 ER PT J AU Zhu, WY Kiss, A De Luca, LM AF Zhu, WY Kiss, A De Luca, LM TI Retinoic acid regulates cell cycle progression and cell cycle related proteins in the human breast carcinoma cell line MCF-7. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, LAB CELLULAR CARCINOGENESIS & TUMOR PROMOT, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 100 EP 100 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800098 ER PT J AU Kostrouch, Z Rall, JE AF Kostrouch, Z Rall, JE TI Expression of CHR3, a member of the steroid/thyroid family of transactivating factors in Caenorhabditis elegans during development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 106 EP 106 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800104 ER PT J AU Mock, YD Kokkonen, GC Roth, GS AF Mock, YD Kokkonen, GC Roth, GS TI Role of protein kinase C activity in epidermal growth factor receptor signal transduction. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA,MOL PHYSIOL & GENET SECT,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 118 EP 118 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800116 ER PT J AU Nguyen, P Ha, MJ Lee, SJ Trepel, JB AF Nguyen, P Ha, MJ Lee, SJ Trepel, JB TI Cytoskeletal localization of the retinoblastoma protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 136 EP 136 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800134 ER PT J AU DellOrco, RT Jupe, ER McClung, JK Liu, XT Rhim, JS Peehl, D Douglas, VD Ralph, D Marley, G Veltri, R Ng, YK AF DellOrco, RT Jupe, ER McClung, JK Liu, XT Rhim, JS Peehl, D Douglas, VD Ralph, D Marley, G Veltri, R Ng, YK TI Differential regulation of prohibitin in prostate cancer cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,FREDERICK,MD 21702. STANFORD UNIV,STANFORD,CA 94305. UROCOR INC,OKLAHOMA CITY,OK 73104. OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 140 EP 140 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800139 ER PT J AU Liyanage, M Weaver, Z Barlow, C duManoir, S McCormack, S Liu, M Green, J Dickson, R WynshawBoris, A Ried, T AF Liyanage, M Weaver, Z Barlow, C duManoir, S McCormack, S Liu, M Green, J Dickson, R WynshawBoris, A Ried, T TI Chromosomal instability in thymic tumors of ataxia telangiectasia knockout mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NCI,FREDERICK,MD 21701. UNIV MARYLAND,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 144 EP 144 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800144 ER PT J AU Palmieri, G White, G Maloid, S Longo, D Ferris, DK AF Palmieri, G White, G Maloid, S Longo, D Ferris, DK TI Analysis of PLK localization domains and function in mammalian cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,SAIC,FREDERICK,MD 21701. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 164 EP 164 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800165 ER PT J AU Castelli, J Hassel, B Wood, K Maran, A Paranjape, J Hewitt, J Li, X Hsu, Y Silverman, R Youle, R AF Castelli, J Hassel, B Wood, K Maran, A Paranjape, J Hewitt, J Li, X Hsu, Y Silverman, R Youle, R TI The role of 2'-5' oligoadenylate-activated RNase L in apoptosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,DEPT CANC BIOL,CLEVELAND,OH 44195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 179 EP 179 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800181 ER PT J AU Gabriele, L Thornton, AM Holmes, K Ozato, K Morse, HC AF Gabriele, L Thornton, AM Holmes, K Ozato, K Morse, HC TI An ICSBP-dependent cell death pathway in hematolymphoid cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20037. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 189 EP 189 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800189 ER PT J AU Fassina, G Noonan, D Aluigi, MG Wong, P Gentleman, S Albini, A AF Fassina, G Noonan, D Aluigi, MG Wong, P Gentleman, S Albini, A TI cAMP analogues induce differentiation and apoptosis in Y-79 retinoblastoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 IST NAZL RIC CANC,I-16132 GENOA,ITALY. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 195 EP 195 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800195 ER PT J AU Wang, F Cremo, CR Facemyer, KC Harvey, EV Sellers, JR AF Wang, F Cremo, CR Facemyer, KC Harvey, EV Sellers, JR TI Preparation of single-headed heavy meromyosin containing two regulatory domains. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. WASHINGTON STATE UNIV,DEPT BIOCHEM & BIOPHYS,PULLMAN,WA 99164. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 207 EP 207 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800207 ER PT J AU Bearer, EL Jaffe, H Medieros, NA Reese, TS AF Bearer, EL Jaffe, H Medieros, NA Reese, TS TI Purification and amino acid sequencing of high molecular weight myosins from squid muscle and optic lobe. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 BROWN UNIV,DEPT PATHOL,PROVIDENCE,RI 02912. MARINE BIOL LAB,WOODS HOLE,MA 02543. NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 215 EP 215 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800214 ER PT J AU VerdierPinard, P Lai, J Falck, J Gerwick, W Hamel, E AF VerdierPinard, P Lai, J Falck, J Gerwick, W Hamel, E TI A structure-activity study of analogs of curacin A, the potent colchicine site antimitotic agent. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOL PHARMACOL LAB,BETHESDA,MD 20892. SW MED SCH,DEPT MOL GENET,DALLAS,TX 75235. OREGON STATE UNIV,COLL PHARM,CORVALLIS,OR 97331. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 262 EP 262 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800261 ER PT J AU Andrews, KL Potdar, P Nettesheim, P Ostrowski, LE AF Andrews, KL Potdar, P Nettesheim, P Ostrowski, LE TI Identification of two novel genes whose expression is upregulated under conditions which promote ciliated cell differentiation of cultured rat tracheal epithelium SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 289 EP 289 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800289 ER PT J AU Fleischmajer, R Utani, A Ninomiya, Y Sado, Y MacDonald, ED Perlish, JS Yamada, Y AF Fleischmajer, R Utani, A Ninomiya, Y Sado, Y MacDonald, ED Perlish, JS Yamada, Y TI There is temporal and spatial expression of collagen IV (C-IV) and laminin (La) 1&5 during development of the basal lamina (BL) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 CUNY MT SINAI SCH MED,DEPT DERMATOL,NEW YORK,NY 10029. NIDR,DEV BIOL LAB,BETHESDA,MD 20814. OKAYAMA UNIV,SCH MED,OKAYAMA 900,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 336 EP 336 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800335 ER PT J AU Bauzon, DE Li, JW Stolow, MA Shi, YB Sang, QXA AF Bauzon, DE Li, JW Stolow, MA Shi, YB Sang, QXA TI Biochemical characterization of a novel collagenase from Xenopus laevis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 FLORIDA STATE UNIV,TALLAHASSEE,FL 32306. NICH,MOL EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 341 EP 341 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800341 ER PT J AU Shi, YB AF Shi, YB TI Regulation of extracellular matrix remodeling and its role in apoptosis and cell renewal during organogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,NIH,LABS MOL EMBRYOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 365 EP 365 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800366 ER PT J AU Wu, C Rajapandi, T AF Wu, C Rajapandi, T TI Characterization of the D10 and K71 mutants of hsp70. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,LCB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 389 EP 389 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800387 ER PT J AU Jiang, RF Barouch, W Eisenberg, E Greene, L AF Jiang, RF Barouch, W Eisenberg, E Greene, L TI Interaction of auxilin and a J-region peptide from auxilin with hsc70. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,LCB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 390 EP 390 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800390 ER PT J AU Presley, JF Cole, NB LippincottSchwartz, J AF Presley, JF Cole, NB LippincottSchwartz, J TI ER-to-Golgi transport of VSV G-GFP chimeras visualized in living cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 427 EP 427 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800429 ER PT J AU Boll, W Ohno, H Songyang, Z Rapoport, I Cantley, L Bonifacino, J Kirchhausen, T AF Boll, W Ohno, H Songyang, Z Rapoport, I Cantley, L Bonifacino, J Kirchhausen, T TI Recognition of tyrosine-based signals by clathrin AP-2 complexes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 459 EP 459 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800460 ER PT J AU Hinshaw, JE AF Hinshaw, JE TI Effects of guanine nucleotides on the structure of dynamin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,DEPT BIOCHEM & CELL BIOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 479 EP 479 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800479 ER PT J AU Ellenberg, J Presley, JF Zaal, KJM Worman, HJ LippincottSchwartz, J AF Ellenberg, J Presley, JF Zaal, KJM Worman, HJ LippincottSchwartz, J TI Diffusional mobility of an inner nuclear membrane protein in mammalian cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,NIH,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 549 EP 549 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800549 ER PT J AU Caracciolo, MR Fang, B Miller, M Hanover, JA AF Caracciolo, MR Fang, B Miller, M Hanover, JA TI Nuclear pore glycoprotein p62 is phosphorylated by glycogen synthase kinase 3, a kinase enriched in the glycogen fraction of Xenopus laevis nuclear reformation extracts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD. WRIGHT STATE UNIV,DEPT BIOL,DAYTON,OH 45435. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 571 EP 571 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800569 ER PT J AU Bhattacharyya, N Dey, A Minucci, S John, S Hager, G Ozato, K AF Bhattacharyya, N Dey, A Minucci, S John, S Hager, G Ozato, K TI Retinoid induced alteration of the chromatin structure in the RAR beta promoter. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 TULARIK INC,NICHD,LAB MOL GROWTH & REGULAT,NIH,S SAN FRANCISCO,CA 94080. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. RI Minucci, Saverio/J-9669-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 587 EP 587 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800586 ER PT J AU Pilch, DR Orr, AH Rogakou, EP Ivanova, VS Bonner, WM AF Pilch, DR Orr, AH Rogakou, EP Ivanova, VS Bonner, WM TI Insights into the function of histones H2AX and H2AZ in chromosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOL PHARMACOL LAB,DBS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 597 EP 597 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800597 ER PT J AU Strunnikov, AV AF Strunnikov, AV TI Functional analysis of the Smc-family proteins in budding yeast. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LAB MOL EMBRYOL,UNIT CHROMOSOME STRUCT & FUNCT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 598 EP 598 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800600 ER PT J AU Rabinovitz, M AF Rabinovitz, M TI Intersection between the glycolytic and protein synthetic pathways in metabolic control: A unifying theory. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 628 EP 628 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800627 ER PT J AU Sakata, H Takayama, H Sharp, R Rubin, JS Merlino, G LaRochelle, WJ AF Sakata, H Takayama, H Sharp, R Rubin, JS Merlino, G LaRochelle, WJ TI Hepatocyte growth factor scatter factor alters liver growth and development in transgenic mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 664 EP 664 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800665 ER PT J AU Wolf, DE Ross, AH McKinnon, C Daou, MC Stephens, RM Kaplan, DR AF Wolf, DE Ross, AH McKinnon, C Daou, MC Stephens, RM Kaplan, DR TI Interaction of GP75 and TRKA nerve growth factor receptors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WORCESTER FDN BIOMED RES,SHREWSBURY,MA 01545. FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. MONTREAL NEUROL INST,MONTREAL,PQ H3A 2B4,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 666 EP 666 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800666 ER PT J AU Engelmann, GL Zeldin, DC AF Engelmann, GL Zeldin, DC TI Expression of arachidonic acid epoxygenase CYP2J3 during heart development: Angiogenic relationship. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 LOYOLA UNIV,DEPT CELL BIOL & MED,MAYWOOD,IL 60153. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 671 EP 671 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800669 ER PT J AU OBrien, DA Welch, JE Bunch, DO Magyar, PL Brown, PR Eddy, EM AF OBrien, DA Welch, JE Bunch, DO Magyar, PL Brown, PR Eddy, EM TI Expression of glyceraldehyde 3-phosphate dehydrogenase-S (GAPD-S) in condensing spermatids. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC 27599. US EPA,RES TRIANGLE PK,NC 27711. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 714 EP 714 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800716 ER PT J AU Dowds, CA Eddy, EM Saling, PM AF Dowds, CA Eddy, EM Saling, PM TI Cloning and characterization of the c-mer receptor tyrosine kinase in the mouse testis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 DUKE UNIV,DEPT CELL BIOL,DURHAM,NC 27710. DUKE UNIV,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 727 EP 727 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800726 ER PT J AU Willard, JM Murphy, DD Beushausen, S AF Willard, JM Murphy, DD Beushausen, S TI Acidic calponin and regulation of neuronal process outgrowth. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 736 EP 736 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800736 ER PT J AU AndresBarquin, PJ Hernandez, MC Hayes, T McKay, R Israel, MA AF AndresBarquin, PJ Hernandez, MC Hayes, T McKay, R Israel, MA TI The expression of ld genes encoding transcriptional inhibitors is regulated during in vitro astrocyte differentiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT NEUROL SURG,SAN FRANCISCO,CA 94143. NINCDS,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 737 EP 737 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800739 ER PT J AU Jin, SJ Gu, XX Rhim, JS Lim, DJ AF Jin, SJ Gu, XX Rhim, JS Lim, DJ TI Immortalization of chinchilla middle ear epithelial cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD,LAB CELLULAR BIOL,ROCKVILLE,MD 20850. NCI,NIH,ROCKVILLE,MD 20850. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 820 EP 820 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800821 ER PT J AU Lee, SB Rao, AK Lee, KH Yang, X Bae, YS Rhee, SG AF Lee, SB Rao, AK Lee, KH Yang, X Bae, YS Rhee, SG TI Decreased expression of phospholipase C-beta 2 in human platelets with impaired function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL SIGNALING LAB,NIH,BETHESDA,MD 20892. TEMPLE UNIV,SCH MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19140. TEMPLE UNIV,SCH MED,DEPT MED,PHILADELPHIA,PA 19140. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 846 EP 846 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800848 ER PT J AU Jamur, MC Hamawy, MM Grodzki, AC Siraganian, RP Oliver, C AF Jamur, MC Hamawy, MM Grodzki, AC Siraganian, RP Oliver, C TI Identification of a putative mast cell precursor using mast cell specific antibody BGD6 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV FED PARANA,DEPT BIOL CELULAR,BR-80060000 CURITIBA,PARANA,BRAZIL. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. OFF NAVAL RES,ARLINGTON,VA 22217. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 876 EP 876 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800875 ER PT J AU Bannantine, JP Rockey, DD Hackstadt, T AF Bannantine, JP Rockey, DD Hackstadt, T TI A search for infection-specific proteins from Chlamydia that may be involved in intracellular trafficking. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST PARASITE INTERACT SECT,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 885 EP 885 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800885 ER PT J AU Shakarian, AM Dwyer, DM AF Shakarian, AM Dwyer, DM TI Biochemical and molecular characterization of a chitinase from Leishmania donovani. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,PARASIT DIS LAB,CELL BIOL SECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 890 EP 890 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800890 ER PT J AU Ward, G SussToby, E Zimmerberg, J AF Ward, G SussToby, E Zimmerberg, J TI A transient change in host cell membrane conductance during invasion by Toxoplasma gondii. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NICHHD,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 897 EP 897 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800897 ER PT J AU Li, WB Becker, KG Jessee, JA Bentham, WD Nagle, JW Gado, A Biddison, WE AF Li, WB Becker, KG Jessee, JA Bentham, WD Nagle, JW Gado, A Biddison, WE TI Motif capture: Isolation and characterization of large cDNA families with genetrapper. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 LIFE TECHNOL INC,GAITHERSBURG,MD 20877. NINCDS,NEUROGENET LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 928 EP 928 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800927 ER PT J AU Lyons, LA Laughlin, TF OBrien, SJ AF Lyons, LA Laughlin, TF OBrien, SJ TI Stratagene Robocycler 96 Gradient Temperature Cycler facilitates comparative gene mapping and the feline genome project SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 934 EP 934 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800933 ER PT J AU Davenport, RW Zhou, RP Thies, E AF Davenport, RW Zhou, RP Thies, E TI Eph receptor tyrosine kinase ligands avert chick retinal ganglion cell axon elongation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. RUTGERS STATE UNIV,CANC RES LAB,PISCATAWAY,NJ 08855. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 989 EP 989 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01800988 ER PT J AU Lee, S Neumann, M Pause, A Zhou, SB Chen, DYT Humphrey, JS Gnarra, JR Pavlakis, G Linehan, WM Klausner, RD AF Lee, S Neumann, M Pause, A Zhou, SB Chen, DYT Humphrey, JS Gnarra, JR Pavlakis, G Linehan, WM Klausner, RD TI Analysis of the cellular localization of the vonHippel-Lindau (VHL) tumor suppressor gene product coupled to the green fluorescent protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELL BIOL & METAB BRANCH,NICHHD,FCRDC,NIH,BETHESDA,MD 20894. NCI,SURG BRANCH,NIH,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1008 EP 1008 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801009 ER PT J AU Arora, JK Zelenka, PS AF Arora, JK Zelenka, PS TI Lens epithelial cells require 12(S)HETE for PKC activation in response to EGF. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1014 EP 1014 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801015 ER PT J AU Sinha, D Paralkar, V Zelenka, P Wistow, G AF Sinha, D Paralkar, V Zelenka, P Wistow, G TI Macrophage migration inhibitory factor (MIF) interacts with pocket proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1070 EP 1070 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801069 ER PT J AU Lorenzi, MV Yamanaka, R Sakaguchi, K Horii, Y Miki, T AF Lorenzi, MV Yamanaka, R Sakaguchi, K Horii, Y Miki, T TI FRAG1, a novel gene that potently activates fibroblast growth factor receptor by C-terminal fusion through chromosomal rearrangement. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NIDR,NIH,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1076 EP 1076 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801075 ER PT J AU SantoniRugiu, E Jensen, MR Thorgeirsson, SS AF SantoniRugiu, E Jensen, MR Thorgeirsson, SS TI Multiple alterations of apoptosis and cell cycle regulation during liver tumor development in c-myc and c-myc/TGF-alpha transgenic mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1095 EP 1095 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801099 ER PT J AU Pirnia, F Nguyen, P Lee, SJ Choi, YH Tsokos, M Srivastava, A Trepel, JB AF Pirnia, F Nguyen, P Lee, SJ Choi, YH Tsokos, M Srivastava, A Trepel, JB TI Rapid induction of differentiation and apoptosis in a primitive neuronal progenitor tumor. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,MED BRANCH,BETHESDA,MD 20892. NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1114 EP 1114 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801114 ER PT J AU BhatiaDey, N Nooruddin, H Conti, MA Taira, M Adelstein, RS AF BhatiaDey, N Nooruddin, H Conti, MA Taira, M Adelstein, RS TI A comparative analysis of nonmuscle myosin in heavy chains A and B during embryonic development of Xenopus laevis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1132 EP 1132 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801130 ER PT J AU Tullio, AN Accili, D Ferrans, VJ Yu, ZX Ward, JM Chan, CC Zimmer, A Westphal, H Preston, YA Adelstein, RS AF Tullio, AN Accili, D Ferrans, VJ Yu, ZX Ward, JM Chan, CC Zimmer, A Westphal, H Preston, YA Adelstein, RS TI Targeted disruption of the gene encoding nonmuscle myosin heavy chain II-B results in structural abnormalities in the mouse heart, brain and retina. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1133 EP 1133 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801132 ER PT J AU Hwang, HK Kawamoto, S Tullio, AN Bridgman, PC Chacko, SK Uren, D Westphal, H Adelstein, RS AF Hwang, HK Kawamoto, S Tullio, AN Bridgman, PC Chacko, SK Uren, D Westphal, H Adelstein, RS TI Null mutation of the neuron-specific, 10 amino acid inserted isoform of mouse nonmuscle myosin II heavy chain-B. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1134 EP 1134 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801139 ER PT J AU Espreafico, EM Coling, DE Kalinec, G Kachar, B AF Espreafico, EM Coling, DE Kalinec, G Kachar, B TI Myosin-V localization in the centrosome and mitotic spindle of animal cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 USP,FMRP,DEPT MORPHOL,BR-14049900 RIBEIRAO PRET,SP,BRAZIL. NIH,NIDCD,LAB CELLULAR BIOL,ROCKVILLE,MD 20850. RI Espreafico, Enilza/O-3053-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1205 EP 1205 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801210 ER PT J AU Muresan, V Abramson, T Lyass, A Winter, D Hong, F Porro, E Zylka, M Morreira, J Zerfas, P Reese, TS Schnapp, BJ AF Muresan, V Abramson, T Lyass, A Winter, D Hong, F Porro, E Zylka, M Morreira, J Zerfas, P Reese, TS Schnapp, BJ TI Interaction of KIF3C, a novel member of the heterodimeric family of kinesin motors, with squid axon vesicles. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NIH,NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1254 EP 1254 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801255 ER PT J AU Gallant, PE Galbraith, JA AF Gallant, PE Galbraith, JA TI Sensitivity and protection of organelle transport after different levels of electrically induced membrane leakage SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,DEPT BIOENGN,SAN DIEGO,CA 92103. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,DEPT MECH ENGN & MAT SCI,DURHAM,NC 27706. BIOL MARINE LAB,WOODS HOLE,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1303 EP 1303 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801302 ER PT J AU Wu, X Bowers, B Wel, Q Kocher, B Hammer, J AF Wu, X Bowers, B Wel, Q Kocher, B Hammer, J TI Myosin V associates with melanosomes in mouse melanocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,LCB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1311 EP 1311 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801313 ER PT J AU Wel, Q Wu, X Hammer, J AF Wel, Q Wu, X Hammer, J TI Cell shape and pigment distribution in wild type and dilute mouse melanocytes in vitro and in situ. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,LCB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1312 EP 1312 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801311 ER PT J AU SonChoi, YS Chung, EK Hong, SI StetlerStevenson, WG AF SonChoi, YS Chung, EK Hong, SI StetlerStevenson, WG TI EGF response on MMPs and TIMPs in SCC 13 cell line was distinct from that of TGF alpha one and the induction pattern was reversed in SCC 12 cell line. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 KOREA CANC CTR HOSP,CELL BIOL LAB,SEOUL 139240,SOUTH KOREA. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1379 EP 1379 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801378 ER PT J AU Liu, LI Rapoport, SI Chandrasekaran, K AF Liu, LI Rapoport, SI Chandrasekaran, K TI Role of sodium and potassium ions in regulation of mitochondrial DNA encoded cytochrome oxidase subunit gene expression in PC12 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1452 EP 1452 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801452 ER PT J AU Ma, W Xian, H Li, YX Barker, JL Coulombe, M Sathanoori, R Hickman, JJ AF Ma, W Xian, H Li, YX Barker, JL Coulombe, M Sathanoori, R Hickman, JJ TI Parallel expressions of BIRK-1 immunoreactivity and depolarization-activated calcium channels in NG108-15 neuroblastoma X glioma hybrid cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 SCI APPLICAT INT CORP,LIFE SCI OPERAT,MCLEAN,VA 22102. NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1461 EP 1461 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801460 ER PT J AU Byeon, M Frankel, AE Westerman, MA Green, JE Papas, TS Henderson, KW Schweinfest, CW AF Byeon, M Frankel, AE Westerman, MA Green, JE Papas, TS Henderson, KW Schweinfest, CW TI Human DRA encodes an intestine-specific sulfate transporter. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. NCI,MOL ONCOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1491 EP 1491 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801490 ER PT J AU Rumsey, SC Kwon, O Xu, W Simpson, I Levine, M AF Rumsey, SC Kwon, O Xu, W Simpson, I Levine, M TI Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1498 EP 1498 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801499 ER PT J AU Lee, J Novoradovskaya, N Brantly, M AF Lee, J Novoradovskaya, N Brantly, M TI A conformational change in alpha 1-antitrypsin induces polymerization and rapid intracellular degradation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,NIH,PCCMB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1536 EP 1536 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801533 ER PT J AU Demaurex, N Furuya, W Bonifacino, JS Grinstein, S AF Demaurex, N Furuya, W Bonifacino, JS Grinstein, S TI pH regulation of the trans-Golgi network: Dynamic pH measurements using retrograde transport of chimeric proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HOSP SICK CHILDREN,DIV CELL BIOL,TORONTO,ON M5G 1X8,CANADA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1546 EP 1546 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801546 ER PT J AU Giattina, MR Miller, JL AF Giattina, MR Miller, JL TI Contact-mediated intercellular transfer of a GPI-linked protein SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1569 EP 1569 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801569 ER PT J AU Balducci, E Horiba, K Usuki, J Ferrand, VJ VanDervort, A Moss, J AF Balducci, E Horiba, K Usuki, J Ferrand, VJ VanDervort, A Moss, J TI Tissue-specific expression and cellular localization of glycosylphosphatidylinositol-anchored NAD:arginine ADP-ribosyltransferase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1575 EP 1575 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801575 ER PT J AU Lewin, DA Ooi, CE Sheff, DR Whitney, JA Yamamoto, EM Bonifacino, JS Mellman, I AF Lewin, DA Ooi, CE Sheff, DR Whitney, JA Yamamoto, EM Bonifacino, JS Mellman, I TI Cloning and characterization of a novel gamma-adaptin-like molecule which may be a component of a Golgi adaptor. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 YALE UNIV,DEPT CELL BIOL,NEW HAVEN,CT. NICHHD,CRMB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1620 EP 1620 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801621 ER PT J AU Broccoli, D Godley, LA Donehower, LA Varmus, HE deLange, T AF Broccoli, D Godley, LA Donehower, LA Varmus, HE deLange, T TI Telomerase activation during mouse mammary tumorigenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,DIV BASIC SCI,NIH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. ROCKEFELLER UNIV,CELL BIOL & GENET LAB,NEW YORK,NY 10021. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1662 EP 1662 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801660 ER PT J AU Saitoh, H Dasso, M AF Saitoh, H Dasso, M TI GTP-dependent and independent associations of RanBP2/Nup358 with Ran, importins, p88 and p18 in Xenopus egg extracts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1686 EP 1686 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801686 ER PT J AU Sweitzer, TD Hanover, JA AF Sweitzer, TD Hanover, JA TI Calmodulin is a GTP-independent activator of nuclear protein import in vitro. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1693 EP 1693 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801690 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Charcot-Leyden crystal protein and galectins have similar gene structures. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1719 EP 1719 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801720 ER PT J AU Grant, DJ OBrian, G Teng, C AF Grant, DJ OBrian, G Teng, C TI Methylation of sequences proximal to the estrogen regulatory site in the mouse lactoferrin gene is influenced by diethylstilbestrol SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1722 EP 1722 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801719 ER PT J AU Tong, ZB Castle, PE Rankin, T Lee, E Nelson, LM Westphal, HJ Dean, J AF Tong, ZB Castle, PE Rankin, T Lee, E Nelson, LM Westphal, HJ Dean, J TI Transgenic mice expressing a human ZP3 minigene assemble a mouse-human chimeric zona pellucida. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1781 EP 1781 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801779 ER PT J AU Novoselov, VV Kuehn, MR AF Novoselov, VV Kuehn, MR TI Expression of functional nodal protein and analysis of activity in embryonic development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. MOSCOW MV LOMONOSOV STATE UNIV,DEPT EMBRYOL,MOSCOW 119899,RUSSIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1805 EP 1805 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801802 ER PT J AU Zaal, KJM Cole, NB Presley, JF Smith, CL LippincottSchwartz, J AF Zaal, KJM Cole, NB Presley, JF Smith, CL LippincottSchwartz, J TI Diffusional mobility of Golgi proteins in mitotic cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1864 EP 1864 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801861 ER PT J AU Terasaki, M Cole, NB AF Terasaki, M Cole, NB TI Dynamics of the Golgi apparatus during early development of sea urchin embryos SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,CBMB,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1865 EP 1865 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801864 ER PT J AU Ralston, E Ploug, T AF Ralston, E Ploug, T TI The organization of the Golgi complex (GC) in skeletal muscle is fiber type dependent. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 RIGSHOSP,COPENHAGEN MUSCLE RES CTR,DK-2100 COPENHAGEN,DENMARK. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1882 EP 1882 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801879 ER PT J AU Nettesheim, P Gray, TE Guzman, K Yoon, JH AF Nettesheim, P Gray, TE Guzman, K Yoon, JH TI Mucous differentiation of human airway epithelium is retinoid independent SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1918 EP 1918 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801914 ER PT J AU Klausner, RD AF Klausner, RD TI Regulating the fate of cytoplasmic mRNAs. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1949 EP 1949 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801946 ER PT J AU Scidmore, MA Rockey, DD Fischer, ER Heinzen, RA Hackstadt, T AF Scidmore, MA Rockey, DD Fischer, ER Heinzen, RA Hackstadt, T TI Vesicular interactions of the Chlamydia trachomatis inclusion are determined by Chlamydial early protein synthesis rather than route of entry. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,NIH,HAMILTON,MT 59840. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1981 EP 1981 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801979 ER PT J AU Finan, PM Soames, CJ Stewart, DM Nelson, DL Kellie, S AF Finan, PM Soames, CJ Stewart, DM Nelson, DL Kellie, S TI Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected SH3 domains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 LITTLEMORE HOSP,YAMANOUCHI RES INST,OXFORD OX4 4XN,ENGLAND. NCI,METAB BRANCH,BETHESDA,MD 20892. RI Kellie, Stuart /A-6036-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 1989 EP 1989 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01801989 ER PT J AU Chang, EY Szallasi, Z Blumberg, PM Rivera, J AF Chang, EY Szallasi, Z Blumberg, PM Rivera, J TI Effects of overexpression of PKC isozymes-alpha, -beta I, -delta, -epsilon, and -eta in the mast cell line RBL-2H3. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract ID EXOCYTOSIS C1 NIAMSD,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2006 EP 2006 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802004 ER PT J AU Gaffen, SL Lai, SY Ha, M Liu, X Hennighausen, L Greene, WC Goldsmith, MA AF Gaffen, SL Lai, SY Ha, M Liu, X Hennighausen, L Greene, WC Goldsmith, MA TI Specificity in interleukin-2 receptor signaling specificity is driven by redundant and multifunctional tyrosine residues of the IL-2R beta chain. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,NIH,GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2054 EP 2054 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802054 ER PT J AU Zhu, DH Dix, D Eddy, EM AF Zhu, DH Dix, D Eddy, EM TI HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. US EPA,NHEERL,REPROD TOXICOL DIV,RES TRIANGLE PK,NC 27711. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2072 EP 2072 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802072 ER PT J AU Qi, CF Chattopadhyay, SK Kim, Y Fredrickson, TN Hartley, JW Morse, HC AF Qi, CF Chattopadhyay, SK Kim, Y Fredrickson, TN Hartley, JW Morse, HC TI Expression of cyclin D1 in mouse B-cell lymphomas of different histological types and differentiation stages. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2126 EP 2126 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802122 ER PT J AU Jensen, MR Factor, VM SantoniRugiu, E AF Jensen, MR Factor, VM SantoniRugiu, E TI Induced cyclin G1 expression after DNA damage in vivo and absence of the protein during mitosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2127 EP 2127 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802125 ER PT J AU He, HY Gao, CY Zhu, Y Zakeri, Z Zelenka, PS AF He, HY Gao, CY Zhu, Y Zakeri, Z Zelenka, PS TI Cyclin dependent kinase activity in differentiating lens fiber cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. CUNY QUEENS COLL,DEPT BIOL,FLUSHING,NY 11367. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2136 EP 2136 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802133 ER PT J AU Huang, JD Russell, LB Copeland, NG Jenkins, NA AF Huang, JD Russell, LB Copeland, NG Jenkins, NA TI Molecular genetic dissection of mouse unconventional myosin V SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MGL,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2157 EP 2157 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802154 ER PT J AU Mermall, V Huang, JD Copeland, NG Jenkins, NA Mooseker, MS AF Mermall, V Huang, JD Copeland, NG Jenkins, NA Mooseker, MS TI Expression and motility of mutant mouse myosin V. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06437. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2159 EP 2159 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802158 ER PT J AU Bonafe, N Odenwald, WF Sellers, JR AF Bonafe, N Odenwald, WF Sellers, JR TI Molecular cloning of myosin-V in Drosophila m: Association with hindgut epithelium in late embryos. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOL CARDIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROGENET UNIT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2161 EP 2161 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802159 ER PT J AU Szczepanowska, J Qin, J Martin, B Korn, ED Brzeska, H AF Szczepanowska, J Qin, J Martin, B Korn, ED Brzeska, H TI Activation of myosin I heavy chain kinase (MIHCK) catalytic domain by phosphorylation and localization of phosphorylation sites. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,LCB,BETHESDA,MD 20892. NHLBI,CHB,BETHESDA,MD 20892. NIMH,CNB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2168 EP 2168 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802163 ER PT J AU Wang, ZY Wang, F Korn, ED Hammer, J AF Wang, ZY Wang, F Korn, ED Hammer, J TI Baculoviral expression of Acanthamoeba myosin IC SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NHLBI,MOL CARDIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2173 EP 2173 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802171 ER PT J AU Hammer, J Lydan, M Jung, G AF Hammer, J Lydan, M Jung, G TI Dictyostelium myoJ associates with membranes of the contractile vacuole complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,LCB,NIH,BETHESDA,MD 20892. UNIV TORONTO,ERINDALE COLL,TORONTO,ON M5S 1A1,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2174 EP 2174 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802169 ER PT J AU Romanova, L Alexandrov, I Nguyen, P Szallazi, Z Nordan, R Blumberg, P Trepel, J Mushinski, JF AF Romanova, L Alexandrov, I Nguyen, P Szallazi, Z Nordan, R Blumberg, P Trepel, J Mushinski, JF TI Crosstalk between PKC-delta and IL-3 pathways: Antagonizing effects on cell shape-controlling actin structures and additive effects on paxillin phosphorylation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2218 EP 2218 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802214 ER PT J AU Ward, RD Robbins, AR AF Ward, RD Robbins, AR TI Increased stability of microtubules in CHO cells expressing mutant GAPDH. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOL & BIOCHEM,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2225 EP 2225 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802223 ER PT J AU Sihag, RK AF Sihag, RK TI Supramolecular organization of neuronal cytoskeleton is regulated by protein phosphorylation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,MCLEAN HOSP,SCH MED,BELMONT,MA 02178. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2230 EP 2230 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802226 ER PT J AU Uren, A Yu, JC Li, WQ Pierce, JH Heidaran, MA AF Uren, A Yu, JC Li, WQ Pierce, JH Heidaran, MA TI Identification of signaling pathways required for PDGF focus-forming activity and cell migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2288 EP 2288 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802285 ER PT J AU Kowalski, RJ Hamel, E AF Kowalski, RJ Hamel, E TI Stimulation of paclitaxel-induced polymerization of tubulin by calcium. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2329 EP 2329 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802323 ER PT J AU Lafrenie, RM Yamada, KM AF Lafrenie, RM Yamada, KM TI Fibronectin or collagen gels induce rapid alterations in epithelial cell gene expression and transcription factor activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2439 EP 2439 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802431 ER PT J AU Shani, N Steel, G Dean, M Valle, D AF Shani, N Steel, G Dean, M Valle, D TI Peroxisomal ATP binding cassette (ABC) transporters heterodimerize. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,KENNEDY KRIEGER INST,DEPT PEDIAT,BALTIMORE,MD 21205. FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2519 EP 2519 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802511 ER PT J AU Kassessinoff, TA Beaven, MA AF Kassessinoff, TA Beaven, MA TI Membrane interactions of N-ethylmaleimide sensitive factor (NSF) in a rat mast cell line. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2587 EP 2587 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802582 ER PT J AU Barr, VA Malide, D Zarnowski, MJ Cushman, SW Taylor, SI AF Barr, VA Malide, D Zarnowski, MJ Cushman, SW Taylor, SI TI Insulin stimulates both the secretion and the production of leptin by white fat tissue SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2608 EP 2608 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802599 ER PT J AU Malide, D Tosh, D Clark, AE Cushman, SW Holman, GD AF Malide, D Tosh, D Clark, AE Cushman, SW Holman, GD TI Altered GLUT4 subcellular trafficking in primary adipose cell cultures: Immunocytochemical evidence. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD,DB,EDMNS,BETHESDA,MD 20892. UNIV BATH,SCH BIOL & BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2636 EP 2636 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802627 ER PT J AU Radhakrishna, H Donaldson, JG AF Radhakrishna, H Donaldson, JG TI Changes in cortical actin affect the cycling of ARF6 between the plasma membrane and a tubular endosomal compartment: Evidence for ARF6 regulation of a novel PM recycling compartment. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2639 EP 2639 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802634 ER PT J AU Hord, NG Phang, JM AF Hord, NG Phang, JM TI Differential effects of lysophosphatidic acid on adherens junction-associated proteins in two murine intestinal epithelial cell lines contrasting in Apc genotype. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB NUTR & MOL REGULAT,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2669 EP 2669 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802663 ER PT J AU Liu, C Ogilvie, MK Chin, K Liu, ZY Noguchi, CT AF Liu, C Ogilvie, MK Chin, K Liu, ZY Noguchi, CT TI Non-hematopoietic erythropoietin receptor promoter-directed expression mimics the pattern observed for myf-5 muscle transcription in the embryonic transgenic mouse SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2724 EP 2724 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802717 ER PT J AU Potdar, P Andrews, KL Nettesheim, P Ostrowski, LE AF Potdar, P Andrews, KL Nettesheim, P Ostrowski, LE TI Expression of gamma-glutamyl-transferase-related (GGT-REL) gene in rat tracheal epithelial cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS,LAB PULM PATH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2744 EP 2744 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802739 ER PT J AU Liu, C Yu, K Chin, K Shen, K Liu, Z Noguchi, CT AF Liu, C Yu, K Chin, K Shen, K Liu, Z Noguchi, CT TI Transgenic mice containing the human erythropoietin receptor gene exhibit correct hematopoietic and neural expression SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2756 EP 2756 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802751 ER PT J AU Lahiri, DK Farlow, MR Greig, NH AF Lahiri, DK Farlow, MR Greig, NH TI Anticholinesterases, phenserine, physostigmine and tacrine. On the secretion of beta-amyloid precursor protein in cell lines. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT NEUROL,INDIANAPOLIS,IN 46202. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2851 EP 2851 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802844 ER PT J AU Tsutsui, T Tanaka, Y Barrett, JC AF Tsutsui, T Tanaka, Y Barrett, JC TI Immortalization of human oral keratinocytes by cotransfection with origin(-)SV40 DNA and c-fos gene. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIPPON DENT UNIV TOKYO,DEPT PHARMACOL,TOKYO 102,JAPAN. NIEHS,MOL CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2860 EP 2860 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802852 ER PT J AU Coso, OA Montaner, S Fromm, C Teramoto, H Gutkind, JS AF Coso, OA Montaner, S Fromm, C Teramoto, H Gutkind, JS TI Signaling from G protein coupled receptors to the c-jun promoter involves the MEF2 transcription factor: Evidence for a novel JNK independent pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR,MSU,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2992 EP 2992 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802985 ER PT J AU Chedid, M Fowler, AG Lengel, C Lee, C Lorenzi, MV Hori, Y Busch, H Chernoff, J Aronson, SA Miki, T AF Chedid, M Fowler, AG Lengel, C Lee, C Lorenzi, MV Hori, Y Busch, H Chernoff, J Aronson, SA Miki, T TI Proliferating-cell nucleolar antigen P40 as an oncoprotein which activates the Rac1/JNK/SRE signaling pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Chernoff, Jonathan/I-7631-2014 OI Chernoff, Jonathan/0000-0002-4803-7836 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 2997 EP 2997 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01802988 ER PT J AU Vanek, PG Balch, RC Wood, KA AF Vanek, PG Balch, RC Wood, KA TI The role of p53 in expression of phosphatidylserine on the cell surface during apoptosis as determined by binding of annexin V. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 TREVIGEN INC,GAITHERSBURG,MD 20877. UNIV CINCINNATI,DEPT CELLULAR & MOL PHYSIOL,CINCINNATI,OH 45267. NINCDS,MOL BIOL UNIT,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3018 EP 3018 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803010 ER PT J AU Paulik, MA Hamacher, LL Yarnall, DP Jennermann, C Maianu, L Pratley, RE Garvey, WT Burns, DK Lenhard, JM AF Paulik, MA Hamacher, LL Yarnall, DP Jennermann, C Maianu, L Pratley, RE Garvey, WT Burns, DK Lenhard, JM TI Identification of Rad's effector-binding domain, intracellular localization and analysis of expression in Pima Indians. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27511. MED UNIV S CAROLINA,DIV ENDOCRINOL,CHARLESTON,SC 29425. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3060 EP 3060 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803051 ER PT J AU Popova, JS Garrison, J Rhee, SG Rasenick, MM AF Popova, JS Garrison, J Rhee, SG Rasenick, MM TI Phospholipase C beta 1 signaling is regulated by tubulin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA 22908. UNIV ILLINOIS,CHICAGO,IL 60612. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3062 EP 3062 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803052 ER PT J AU Akar, CA Wallace, WC AF Akar, CA Wallace, WC TI Molecular interactions between amyloid precursor protein and NGF that underlie potentiation of neurotrophic activity. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3083 EP 3083 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803073 ER PT J AU Kim, PJ Day, R Sakaguchi, K Sakamoto, H Saxinger, C McPhie, P Rubin, JS Bottaro, DP AF Kim, PJ Day, R Sakaguchi, K Sakamoto, H Saxinger, C McPhie, P Rubin, JS Bottaro, DP TI Relationship between structure and function of keratinocyte growth factor. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3085 EP 3085 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803074 ER PT J AU Song, J Radhakrishna, H Donaldson, JG AF Song, J Radhakrishna, H Donaldson, JG TI Endogenous ARF6 localizes to sites of cortical actin rearrangements during cell spreading and in cells treated with phorbol esters. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3195 EP 3195 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803183 ER PT J AU Jarnik, M Leapman, RD Simon, MN Steven, AC AF Jarnik, M Leapman, RD Simon, MN Steven, AC TI Cornified cell envelope assembly studied by mass- and element-specific EM SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMSD,LSBR,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,UPTON,NY 11973. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3217 EP 3217 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803208 ER PT J AU Prahlad, V Steinert, P Marekov, L Goldman, RD AF Prahlad, V Steinert, P Marekov, L Goldman, RD TI The purification and characterization of a nestin-like protein from baby hamster kidney (BHK) cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3244 EP 3244 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803234 ER PT J AU Patton, WA Hong, JX Yoo, HS Lee, FJS Zhang, GF Han, JS Chung, JK Donaldson, J Rhee, SG Moss, J Vaughan, M AF Patton, WA Hong, JX Yoo, HS Lee, FJS Zhang, GF Han, JS Chung, JK Donaldson, J Rhee, SG Moss, J Vaughan, M TI Residues within ADP-ribosylation factor (ARF1) and ADP-ribosylation factor-like (ARL1) proteins play a role in phospholipase D (PLD) activation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NHLBI,LAB CELL SIGNALLING,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3455 EP 3455 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803443 ER PT J AU Newitt, JA Bernstein, HD AF Newitt, JA Bernstein, HD TI Mutations in the N-domain of the signal recognition particle 54-kilodalton subunit reduce signal sequence binding but do not affect translocation activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3583 EP 3583 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803571 ER PT J AU Handen, JS Rosenberg, HF AF Handen, JS Rosenberg, HF TI A NFAT1 consensus site mediates optimal expression of the eosinophil-derived neurotoxin gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3674 EP 3674 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803665 ER PT J AU Li, J Schechter, AN Noguchi, CT AF Li, J Schechter, AN Noguchi, CT TI Negative regulatory elements in transcription of the human epsilon globin gene. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3678 EP 3678 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803667 ER PT J AU Li, J Ikonomi, P Peters, B Brown, CE Schechter, AN Noguchi, CT AF Li, J Ikonomi, P Peters, B Brown, CE Schechter, AN Noguchi, CT TI Transgenic and cellular assays of human epsilon globin silencer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3679 EP 3679 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803668 ER PT J AU Tarcsa, E Marekov, LN Mei, G Melino, G Steinert, PM AF Tarcsa, E Marekov, LN Mei, G Melino, G Steinert, PM TI Evidence that peptidylarginine deiminase functions as an anti-chaperonin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,DEPT EXPT MED,I-00167 ROME,ITALY. IRCCS,IDI,I-00167 ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3695 EP 3695 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803682 ER PT J AU Yamada, S Kuehn, MR AF Yamada, S Kuehn, MR TI Analysis of novel insertional mutations disrupting mouse embryogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3732 EP 3732 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803721 ER PT J AU Ewart, JL Melloy, PG Cohen, MF Desmond, ME Kuehn, MR Lo, CW AF Ewart, JL Melloy, PG Cohen, MF Desmond, ME Kuehn, MR Lo, CW TI No turning, a mutation causing laterality defects in mouse embryos. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104. VILLANOVA UNIV,DEPT BIOL,VILLANOVA,PA. NICHHD,MOL GENET LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3739 EP 3739 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803729 ER PT J AU Frey, WH Venters, HD Bonilla, LE Najarian, MM Ala, TA Mason, RP AF Frey, WH Venters, HD Bonilla, LE Najarian, MM Ala, TA Mason, RP TI Heme compounds from Alzheimer's brain inhibit muscarinic receptor binding via thm radical generation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 RAMSEY CLIN HLTH PARTNERS,ST PAUL,MN 55101. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3765 EP 3765 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803751 ER PT J AU Kalinec, F Kalinec, GM Kachar, B AF Kalinec, F Kalinec, GM Kachar, B TI Cloning and characterization of inner ear cell lines derived from transgenic mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD,SECT STRUCT CELL BIOL,LCB,NIH,ROCKVILLE,MD 20850. HOUSE EAR RES INST,CELLULAR & MOL BIOL LAB,LOS ANGELES,CA 90057. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3782 EP 3782 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803768 ER PT J AU Grant, P Brady, D Veeranna Sharma, P Sharma, M Pant, HC AF Grant, P Brady, D Veeranna Sharma, P Sharma, M Pant, HC TI Down regulation of kinase activities in Alzheimer brains. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINCDS,LNC,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3790 EP 3790 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803778 ER PT J AU Lee, MK Borchelt, D Thinakaran, G Slunt, H Kim, G Ratoviski, T Martin, L Gandy, S Levey, A Jenkins, N Copeland, N Price, DL Sisodia, SS AF Lee, MK Borchelt, D Thinakaran, G Slunt, H Kim, G Ratoviski, T Martin, L Gandy, S Levey, A Jenkins, N Copeland, N Price, DL Sisodia, SS TI Expression and endoproteolytic processing of wild type and FAD-linked mutant presenilin 1 in transgenic mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. CORNELL UNIV MED COLL,NEW YORK,NY. EMORY UNIV,ATLANTA,GA 30322. NCI,MAMMALIAN GENET LAB,FREDERICK,MD 21701. RI Lee, Michael/D-9491-2013 OI Lee, Michael/0000-0001-5865-9682 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3797 EP 3797 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803787 ER PT J AU Dosemeci, A Choi, C AF Dosemeci, A Choi, C TI Ca2+-independent autophosphorylation of postsynaptic density-associated CaM kinase II SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3802 EP 3802 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803790 ER PT J AU Kurc, M Dodane, V Pinto, D Kachar, B AF Kurc, M Dodane, V Pinto, D Kachar, B TI Presynaptic localization of G alpha q/11 in efferent terminals of the cochlea. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD,NIH,BETHESDA,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3807 EP 3807 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803795 ER PT J AU Sathyamoorthy, M deMendez, I Adams, AG Leto, TL AF Sathyamoorthy, M deMendez, I Adams, AG Leto, TL TI P40-phox down-regulates NADPH oxidase activity through its SH3 domain. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3813 EP 3813 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803801 ER PT J AU Shen, FS Loh, YP AF Shen, FS Loh, YP TI Aberrant processing and secretion of proopiomelanocortin pituitary cells of fat/fat mice carrying a mutated carboxypeptidase E gene. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD,LDN,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1996 VL 7 SU S BP 3832 EP 3832 PG 1 WC Cell Biology SC Cell Biology GA WB018 UT WOS:A1996WB01803822 ER PT J AU Shou, MG Korzekwa, KR Krausz, KW Buters, JTM Grogan, J Goldfarb, I Hardwick, JP Gonzalez, FJ Gelboin, HV AF Shou, MG Korzekwa, KR Krausz, KW Buters, JTM Grogan, J Goldfarb, I Hardwick, JP Gonzalez, FJ Gelboin, HV TI Specificity of cDNA-expressed human and rodent cytochrome P450s in the oxidative metabolism of the potent carcinogen 7,12-dimethylbenz[a]anthracene SO MOLECULAR CARCINOGENESIS LA English DT Article DE 7,12-dimethylbenz[a]anthracene; metabolism of polycyclic aromatic hydrocarbons; cytochrome P450; cDNA expression; high-performance liquid chromatography ID LUNG-CANCER; 7,12-DIMETHYLBENZANTHRACENE METABOLITES; LIVER MICROSOMES; VACCINIA VIRUS; HUMAN-TISSUES; MOUSE SKIN; 7,12-DIMETHYLBENZ(A)ANTHRACENE; PURIFICATION; BINDING; RAT AB 7,12-Dimethylbenz[a]anthracene (DMBA), a potent carcinogen, requires metabolic activation by cytochrome P450s (P450s) to electrophilic metabolites that result in DNA modification, mutagenicity, and carcinogenicity. In this study, we used eight human forms, four rodent forms, and one rabbit form of P450 expressed from recombinant vaccinia or baculovirus vectors to define their specificity for metabolizing DMBA. Of the eight human P450s, 1A1 was the most active (specific activity = 14.7 nmol/min/nmol of P450) in total metabolism of DMBA and showed approximately 6- to 33-fold more activity than other P450s. 2B6, 2C9, and 1A2 were also capable of metabolizing DMBA (2.0-2.5 nmol/min/nmol of P450), whereas 2C8, 2E1, 3A4, and 3A5 exhibited relatively low activities. Among animal P450s, mouse 1A1 exhibited activity similar to that of human 1A1 and had 5.0- to 37-fold more activity than other rodent and rabbit P450s. In regard to enzyme regioselectivity, most human and rodent P450s predominantly formed the 8,9-diol, but human 2B6 and rat 2B1 preferentially formed the 5,6-diol. In the production of monohydroxymethyl metabolites, all the enzymes yielded more 7-hydroxymethyl-12-methylbenz[a]anthracene (7HOM12MBA) than 12-hydroxymethyl-7-methylbenz[a]anthracene (7M12HOMBA), except for human 1A1, which presented the reverse selectivity. Human liver microsomes from 10 organ donors were shown to metabolize DM BA and in most circumstances generated the meta belie profile DM BA trans-8,9-d dihydrodiol > 7HOM12MBA greater than or equal to DMBA trans-5,6-dihydrodiol greater than or equal to 7,12-dihydroxymethylbenz[a]anthracene > 7M12HOMBA > DMBA trans-3,4-dihydrodiol. Thus, the combined activity of hepatic microsomal 2C9, 1A2, and 2B6 may contribute to the metabolic activation and the metabolism of DMBA in normal human liver. (C) 1996 Wiley-Liss, Inc. C1 NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. RP Shou, MG (reprint author), NCI,MOL CARCINOGENESIS LAB,NIH,BLDG 37,RM 3E24,BETHESDA,MD 20892, USA. RI Buters, Jeroen/G-5070-2011 NR 44 TC 44 Z9 44 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 DEC PY 1996 VL 17 IS 4 BP 241 EP 249 DI 10.1002/(SICI)1098-2744(199612)17:4<241::AID-MC8>3.0.CO;2-G PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WA018 UT WOS:A1996WA01800009 PM 8989918 ER PT J AU Liu, XW Robinson, GW Hennighausen, L AF Liu, XW Robinson, GW Hennighausen, L TI Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; COLONY-STIMULATING FACTOR; GROWTH-HORMONE; EPITHELIAL-CELLS; GENE-EXPRESSION; TRANSCRIPTION FACTOR; NUCLEAR TRANSLOCATION; CYTOKINE RECEPTORS; PLACENTAL-LACTOGEN; STAT5-LIKE FACTOR AB Signal transducer and activator of transcription (Stat)5 was originally identified as a mammary gland factor (MGF) that binds to promoter sequences of milk protein genes and activates their transcription. We have generated isoform-specific antibodies against Stat5a or Stat5b and show that both isoforms are present in similar amounts at the protein level in mammary tissues of virgin, pregnant, lactating, and involuting mice. in contrast, State phosphorylation is very low in immature virgins, rises sharply during late pregnancy, and declines rapidly during involution. Upon phosphorylation, Stat5a and Stat5b form homo- and heterodimers. The induction of State phosphorylation during late pregnancy correlates with the transcriptional activation of milk protein genes. Using electrophoretic mobility shift assay and supershift analysis, we demonstrated that the DNA-binding activity detected during lactation is composed of both Stat5a and Stat5b, but not of other STATs. The hypothesis that State is directly involved in mammary cell differentiation was tested in estrous cycle and in transgenic mice with impaired mammary development. Transient differentiation of mammary alveolar cells and milk protein gene expression during estrus in virgin female mice coincide with transient state phosphorylation. Impaired mammary development and very low levels of milk protein gene expression in mice carrying the truncated form of the cell fate protein Int3 correlated with reduced phosphorylation and heterodimer formation. C1 NIDDKD, BIOCHEM & METAB LAB, NIH, BETHESDA, MD 20892 USA. RI Robinson, Gertraud/I-2136-2012 NR 62 TC 189 Z9 191 U1 1 U2 2 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 DEC PY 1996 VL 10 IS 12 BP 1496 EP 1506 DI 10.1210/me.10.12.1496 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW494 UT WOS:A1996VW49400002 PM 8961260 ER PT J AU Gage, PJ Brinkmeier, ML Scarlett, LM Knapp, LT Camper, SA Mahon, KA AF Gage, PJ Brinkmeier, ML Scarlett, LM Knapp, LT Camper, SA Mahon, KA TI The Ames dwarf gene, df, is required early in pituitary ontogeny for the extinction of Rpx transcription and initiation of lineage-specific cell proliferation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE; TRANSGENIC MICE; RATHKES POUCH; EXPRESSION; MUTATION; PIT-1; DIFFERENTIATION; COMMITMENT; ABLATION; INVITRO AB Two nonallelic dwarfing mutations in mice define genes important for pituitary development and function. Mice homozygous for either the Ames (df) or Snell (Pit1(dw)) dwarf mutations exhibit severe proportional dwarfism, hypothyroidism, and infertility due to the cytodifferentiation failure of three anterior pituitary cell types: thyrotropes, somatotropes, and lactotropes. Analysis of double heterozygotes and double mutants has provided evidence that the df and dw genes act sequentially in the same genetic pathway. Double heterozygotes had no reduction in growth rate or final adult size. Double homozygotes had essentially the same phenotype as the single mutants and were recovered at the predicted frequency, indicating that there are no previously unrecognized, redundant functions of the two genes. Several lines of evidence demonstrate that df acts earlier in the differentiation pathway than Pit1. The df mutants fail to extinguish expression of the homeobox gene Rpx on embryonic day 13.5 (e13.5), and the size of their nascent pituitary glands is reduced by e14.5. In contrast, Pit1(dw) mutants down-regulate Rpx appropriately and exhibit normal cell proliferation up to e14.5. The failure to extinguish Rpx and the concomitant hypocellutarity of df pituitaries suggest the importance of Rpx repression in lineage-specific cell proliferation before the appearance of lineage-specific markers. Later, Pit-1 and hypothalamic neuropeptides act sequentially to regulate marker gene transcription and cell proliferation. These results establish the time of df action in a cascade of genes that regulate pituitary ontogeny. C1 UNIV MICHIGAN, SCH MED, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, SCH MED, MOL & CELLULAR BIOL PROGRAM, ANN ARBOR, MI 48109 USA. NICHHD, LAB MAMMALIAN GENES & DEV, NIH, BETHESDA, MD 20892 USA. OI Gage, Philip/0000-0001-5536-6702; Camper, Sally/0000-0001-8556-3379 FU NICHD NIH HHS [HD-30428]; NIDDK NIH HHS [DK-0724-5-18]; OGDP CDC HHS [GD-07274] NR 59 TC 122 Z9 123 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 DEC PY 1996 VL 10 IS 12 BP 1570 EP 1581 DI 10.1210/me.10.12.1570 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VW494 UT WOS:A1996VW49400009 PM 8961267 ER PT J AU Chen, HT Alexander, CB Chen, FF Mage, RG AF Chen, HT Alexander, CB Chen, FF Mage, RG TI Rabbit DQ52 and D-H gene expression in early B-cell development SO MOLECULAR IMMUNOLOGY LA English DT Article DE rabbit; B-lymphocytes; gene rearrangement; cellular differentiation; generation of diversity ID HEAVY-CHAIN LOCUS; PROXIMAL D-SEGMENT; PREFERENTIAL UTILIZATION; ANTIBODY REPERTOIRE; V(D)J RECOMBINATION; FETAL; VH; DIVERSITY; LINE; JH AB Rabbits predominantly rearrange the most 3' V-H gene (VH1); thus combinatorial diversity is very limited. In man and mouse, the most 3' D-H gene, DQ52, is preferentially rearranged early in B-cell development. To test whether this preference for rearranging a D-H gene segment based on 3' end proximity exists in rabbit, we cloned and sequenced the rabbit DQ52 gene. The 11 base pair coding region sequence is identical to a published mouse DQ52, and 81.8% similar to the human sequence. It is localized similar to 805 bp upstream of the J(H)1 gene. However, the 3' recombination signal sequence has an atypical nonamer. We prepared mRNA from 15- to 28-day fetal rabbits and amplified expressed VDJ sequences of mu mRNA by RT-PCR. The PCR products with VDJ rearrangements were cloned and sequenced. As expected, 44 of 45 VDJ sequences reflected use of the 3' V(H)1a2 gene, but the DQ52 gene was utilized very infrequently, if at all. We found only one VDJ sequence from 28-day fetal liver B-cells with 8 bp that matched the germline DQ52 sequence. Instead of expressing DQ52, another D-H gene, Df was frequently expressed. We cloned the genomic Df gene and localized it about 32 kb upstream of the J(H) region. Thus, in contrast to man and mouse, rabbits preferentially express a DH gene located in the middle of the D-H region early in B cell ontogeny. This may correlate with more frequent initial rearrangement of V-H to D-H in rabbit B cells. C1 NIAID,MOL IMMUNOGENET SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 44 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 1996 VL 33 IS 17-18 BP 1313 EP 1321 DI 10.1016/S0161-5890(96)00107-1 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA WZ464 UT WOS:A1996WZ46400005 PM 9171891 ER PT J AU Fujimori, A Gupta, M Hoki, Y Pommier, Y AF Fujimori, A Gupta, M Hoki, Y Pommier, Y TI Acquired camptothecin resistance of human breast cancer MCF-7/C4 cells with normal topoisomerase I and elevated DNA repair SO MOLECULAR PHARMACOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; HAMSTER DC3F CELLS; REPLICATION FORKS; CLEAVABLE COMPLEXES; MAMMALIAN-CELLS; SENSITIVITY; INHIBITORS; MUTATION; MUTANTS; DAMAGE AB A camptothecin (CPT)-resistant cell line (MCF-7/C4) was established from MCF-7 cells by mutagenic treatment with methylmethanesulfonate and selection with CPT. MCF-7/C4 is 30-fold resistant to CPT and is cross-resistant to UV and cis-dichlorodiammineplatinum(II) but not to VP-16 or ionizing radiation. Topoisomerase I (top1)-mediated cleavable complexes in the presence of CPT, measured by oligonucleotide assay and by alkaline elution, were similar in both cell lines. Other top1 parameters such as top1 protein, RNA levels, and DNA relaxation were also similar in both cell lines. Thus, CPT resistance is not due to alterations in top1 activity but is caused by changes in the downstream pathways from the top1-induced damage. Both cell lines had similar doubling time (22 hr), but MCF-7/C4 cells showed reduced S-phase fraction in the absence of CPT and reduced G(2) delay after CPT treatment. p53, GADD45, and p21(WAF1/CIP1) were induced similarly by CPT in both cell lines. The overall repair capacity estimated by the ability of cells to reactivate UV-damaged pSV-CAT plasmid was increased in MCF-7/C4 cells. These observations suggest that enhanced DNA repair is one of the factors involved in CPT resistance. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 43 TC 32 Z9 32 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 DEC PY 1996 VL 50 IS 6 BP 1472 EP 1478 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VZ335 UT WOS:A1996VZ33500006 PM 8967967 ER PT J AU Andrews, AM Ladenheim, B Epstein, CJ Cadet, JL Murphy, DL AF Andrews, AM Ladenheim, B Epstein, CJ Cadet, JL Murphy, DL TI Transgenic mice with high levels of superoxide dismutase activity are protected from the neurotoxic effects of 2'-NH2-MPTP on serotonergic and noradrenergic nerve terminals SO MOLECULAR PHARMACOLOGY LA English DT Article ID FLUORINATED 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ANALOGS; STRIATAL DOPAMINE; 1-METHYL-4-PHENYLPYRIDINIUM MPP+; PARA-CHLOROAMPHETAMINE; HIPPOCAMPAL SEROTONIN; CHRONIC PARKINSONISM; BRAIN MITOCHONDRIA; MONOAMINE-OXIDASE; MPTP; METHAMPHETAMINE AB Administration of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analog 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP; 4 x 15 mg/kg) to CD-1 mice was found to cause substantial decreases in cortical and hippocampal 5-hydroxytryptamine (5-HT) and norepinephrine (NE) to 20-30% of control 3 weeks after treatment. The magnitude of these depletions was similar to those reported previously in Swiss Webster and C57BL/6 mice given 4 x 20 mg/kg 2'-NH2-MPTP, and in keeping with these prior studies, striatal dopamine levels were unchanged by 2'-NH2-MPTP treatment in CD-1 mice. Subsequently, transgenic CD-I mice producing high levels of human cytosolic Cu-Zn superoxide dismutase (SOD) were studied to assess the role of oxygen radicals in the mechanism of action of 2'-NH2-MPTP. In contrast to the results described above, 5-HT and NE levels were almost completely unaffected by 2'-NH2-MPTP treatment in homozygous SOD mice bearing 5-fold increases in brain SOD activity. In 2'-NH2-MPTP-treated heterozygous SOD mice, which showed an average 3-fold increase in brain SOD activity, only moderate depletions in cortical and hippocampal 5-HT (50-60% of control) and NE (30-40% of control) were observed. Additionally, the density of [I-125]RTI-55-labeled 5-HT uptake sites was studied to further assess possible 5-HT terminal loss. In various cortical and hippocampal subregions of nontransgenic mice, 5-HT uptake sites were reduced to 20-35% of control after 2'-NH2-MPTP treatment, in comparison with homozygous SOD mice, which were affected only minimally by 2'-NH2-MPTP administration, and heterozygous SOD mice, which showed intermediate reductions in 5-HT uptake site density on the order of 55-80% of control. Together, these data indicate that mice genetically endowed with increased SOD activity are protected from 2'-NH2-MPTP-induced toxicity, thereby implicating superoxide radicals in the mechanism of action of a neurotoxin that selectively depletes 5-HT and NE without affecting dopamine. C1 NIDA,MOL NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. RP Andrews, AM (reprint author), NIMH,CLIN SCI LAB,10-3D-41,10 CTR DR,MSC 1264,BETHESDA,MD 20892, USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 55 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 DEC PY 1996 VL 50 IS 6 BP 1511 EP 1519 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VZ335 UT WOS:A1996VZ33500011 PM 8967972 ER PT J AU Reszka, KJ Chignell, CF AF Reszka, KJ Chignell, CF TI Acid-catalyzed oxidation of the anticancer agent mitoxantrone by nitrite ions SO MOLECULAR PHARMACOLOGY LA English DT Article ID NITROUS-ACID; MODEL SYSTEMS; BREAST-CANCER; L-ARGININE; OXIDE; MECHANISM; KINETICS; PH; TRANSFORMATION; CYTOTOXICITY AB Mitoxantrone (1,4-dihydroxy-5,8-bis{2-[(2-hydroxyethyl)amino-]ethyl}amino-9,10-anthracenedione; MXH(2)) is a novel anticancer agent that is useful in the treatment of leukemia and breast cancer. In contrast to other anthracenedione-based agents, this drug causes fewer side effects, mainly because it is resistant to metabolic reduction. We investigated the interaction between MXH(2) and inorganic nitrite (NO2-) in aqueous solutions and found that this drug undergoes acid-catalyzed oxidation by nitrite. The rate of this reaction measured Versus [NaNO2] at constant pH or versus pH at constant [NaNO2] was found to be directly proportional to the actual HNO2 concentration, indicating HNO2 to be the major oxidizing species. Involvement of (NO)-N-. and/or NO2. radicals as minor oxidants is suggested based on the dependence of the rate of oxidation on the presence of air. Spectrophotometric and electron paramagnetic resonance analyses indicate that early products of the reaction are identical to those generated by oxidation of MXH(2) by a horseradish peroxidase/hydrogen peroxide system. The major product is hexahydronaphtho[2,3-f]quinoxaline-7,12-dione, which is formed by intramolecular cyclization of one alkylamino side chain in the oxidized, diiminoquinone MX(N) form of the drug. This study shows that MXH(2) effectively scavenges HNO2 and possibly other nitrogen oxides. Because these reactive forms of nitrogen may be present in vivo, this property of the drug may be relevant to its biological or perhaps anticancer activities. RP Reszka, KJ (reprint author), NIEHS,MOL BIOPHYS LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 6 Z9 6 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1996 VL 50 IS 6 BP 1612 EP 1618 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VZ335 UT WOS:A1996VZ33500023 PM 8967984 ER PT J AU Varga, EV Li, XP Stropova, D Zalewska, T Landsman, RS Knapp, RJ Malatynska, E Kawai, K Mizusura, A Nagase, H Calderon, SN Rice, K Hruby, VJ Roeske, WR Yamamura, HI AF Varga, EV Li, XP Stropova, D Zalewska, T Landsman, RS Knapp, RJ Malatynska, E Kawai, K Mizusura, A Nagase, H Calderon, SN Rice, K Hruby, VJ Roeske, WR Yamamura, HI TI The third extracellular loop of the human delta-opioid receptor determines the selectivity of delta-opioid agonists SO MOLECULAR PHARMACOLOGY LA English DT Article ID BINDING; DISTINGUISHES; DOMAINS; LIGAND; DAMGO; CDNA; SITE AB In the present study, we replaced the third extracellular loop of the human delta-opioid receptor with that of the human mu-opioid receptor. A modified polymerase chain reaction overlap extension method was used to achieve the exact splicing in the chimera to show the importance of the extracellular loop in ligand binding without interference from transmembrane substitutions. The replacement of the third extracellular loop did not alter the affinity of [H-3]diprenorphine but caused a dramatic decrease in the affinity of both the delta-selective peptide agonists cyclo[D-Pen(2),4'Cl-Phe(4),D-Pen(5)]enkephalin and deltorphin II and the delta-selective nonpeptide agonists SNC 121 and (-)TAN 67. The affinities of the mu-selective peptide agonist [D-Ala(2)-MePhe(4)-Gly-ol(5)]enkephalin and the mu-preferring nonpeptide agonist morphine were not affected. Site-directed mutagenesis studies show that the mechanism of ligand recognition might be different for each structural class of opioid ligands. C1 UNIV ARIZONA,HLTH SCI CTR,COLL MED,DEPT PHARMACOL,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,DEPT BIOCHEM,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,DEPT PSYCHIAT,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,DEPT MED,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,DEPT CHEM,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,PROGRAM NEUROSCI,TUCSON,AZ 85724. TORAY INDUSTRIES LTD,BASIC RES LABS,KAMAKURA,KANAGAWA 24,JAPAN. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 23 TC 42 Z9 44 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1996 VL 50 IS 6 BP 1619 EP 1624 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VZ335 UT WOS:A1996VZ33500024 PM 8967985 ER PT J AU Masuda, R Lopez, JV Slattery, JP Yuhki, N OBrien, SJ AF Masuda, R Lopez, JV Slattery, JP Yuhki, N OBrien, SJ TI Molecular phylogeny of mitochondrial cytochrome b and 125 rRNA sequences in the Felidae: Ocelot and domestic cat lineages SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID 23S RIBOSOMAL-RNA; EVOLUTIONARY RATES; DNA; GENOME; VERTEBRATES; DISTANCE; GENE; AMPLIFICATION; CARNIVORA; UTILITY AB Molecular phylogeny of the cat family Felidae is derived using two mitochondrial genes, cytochrome b and 12S rRNA. Phylogenetic methods of weighted maximum parsimony and minimum evolution estimated by neighbor-joining are employed to reconstruct topologies among 20 extant felid species. Sequence analyses of 363 bp of cytochrome b and 376 bp of the 12S rRNA genes yielded average pair-wise similarity values between felids ranging from 94 to 99% and from 85 to 99%, respectively. Phylogenetic reconstruction supports more recent, intralineage associations but fails to completely resolve interlineage relationships. Both genes produce a monophyletic group of Felis species but vary in the placement of the pallas cat. The ocelot lineage represents an early divergence within the Felidae, with strong associations between ocelot and margay, Geoffroy's cat and kodkod, and pampas cat and tigrina. Implications of the relative recency of felid evolution, presence of ancestral polymorphisms, and influence of outgroups in placement of the topological root are discussed. (C) 1996 Academic Press, Inc. C1 HOKKAIDO UNIV, FAC SCI, CHROMOSOME RES UNIT, KITA KU, SAPPORO, HOKKAIDO 060, JAPAN. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, BCDP, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, LAB GENOM DIVERS, FREDERICK, MD 21702 USA. RI Lopez, Jose/F-8809-2011; MASUDA, RYUICHI/G-5223-2012 OI Lopez, Jose/0000-0002-1637-4125; NR 62 TC 43 Z9 52 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 EI 1095-9513 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD DEC PY 1996 VL 6 IS 3 BP 351 EP 365 DI 10.1006/mpev.1996.0085 PG 15 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA WB057 UT WOS:A1996WB05700003 PM 8975691 ER PT J AU Licinio, J AF Licinio, J TI Molecular Psychiatry: One year of experience SO MOLECULAR PSYCHIATRY LA English DT Editorial Material RP Licinio, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,RM 3S231,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 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 DEC PY 1996 VL 1 IS 6 BP 419 EP 420 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VZ757 UT WOS:A1996VZ75700001 ER PT J AU Akiskal, HS Bolis, CL Cazzullo, C Silva, JACE Gentil, V Lecrubier, Y Licinio, J Linden, M LopezIbor, JJ Ndiaye, IP Pani, L Prilipko, L Robertson, MM Robinson, RG Starkstein, SE Thomas, P Wang, Y Wong, ML AF Akiskal, HS Bolis, CL Cazzullo, C Silva, JACE Gentil, V Lecrubier, Y Licinio, J Linden, M LopezIbor, JJ Ndiaye, IP Pani, L Prilipko, L Robertson, MM Robinson, RG Starkstein, SE Thomas, P Wang, Y Wong, ML TI Dysthymia in neurological disorders SO MOLECULAR PSYCHIATRY LA English DT Editorial Material DE dysthymia; nervous system diseases; multiple sclerosis; stroke; Parkinson's disease; Alzheimer's disease; epilepsy; classification; imaging techniques; corticotropin-releasing hormone; dopamine ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE-RESPONSIVE ELEMENT; TEMPORAL-LOBE EPILEPSY; MULTIPLE-SCLEROSIS; STROKE PATIENTS; BIOCHEMICAL MANIFESTATIONS; DEPRESSIVE-DISORDERS; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; MOOD DISORDERS AB Dysthymia is characterized by long-lasting periods of lowered mood, Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Ifs pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is ifs co-occurrence with medical and neurological disorders. A World Health Organization meeting on dysthymia in neurological disorders was held in Geneva, 1-3 July 1996 to address this topic, Some of the major goals of this meeting were to clarify the definition of dysthymia in the presence of neurological disorders and to evaluate current research in the field, to point out new areas for investigation, and to discuss current psychological and pharmacological treatments for dysthymia in neurological disorders, The potential roles of neuroendocrine and molecular mechanisms in dysthymia were identified through specific problems related to dysthymia occurring in disorders such as Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and epilepsy. This meeting provided direction and opportunity for future studies in the under-recognized and under-investigated relationship between dysthymia and neurological disorders. C1 NIMH, UNIT CLIN RES,CLIN NEUROENDOCRINOL BRANCH, INTRAMURAL RES PROGRAM,NIH, BETHESDA, MD 20892 USA. UNIV CALIF SAN DIEGO, SCH MED, SAN DIEGO, CA 92103 USA. WHO SECRETARIAT, DIV MENTAL HLTH & PREVENT SUBSTANCE ABUSE, GENEVA, SWITZERLAND. PRO JUVENTUDE FDN DON CARLO GNOCCHI, MULTIPLE SCLEROSIS UNIT, I-20122 MILAN, ITALY. UNIV SAO PAULO, FAC MED, DEPT PSIQUITRIA, BR-01000 SAO PAULO, BRAZIL. HOP LA PITIE SALPETRIERE, F-75651 PARIS 13, FRANCE. FREE UNIV BERLIN, PSYCHIAT KLIN & POLIKLIN, D-14050 BERLIN, GERMANY. UNIV COMPLUTENSE MADRID, HOSP CLIN SAN CARLOS, MADRID, SPAIN. CTR HOSP UNIV FANN, SERV NEUROL, DAKAR, SENEGAL. CNR, BERNARD B BRODIE DEPT NEUROSCI, I-09124 CAGLIARI, ITALY. CNR, CTR NEUROPHARMACOL, I-09124 CAGLIARI, ITALY. UNIV CAGLIARI, I-09124 CAGLIARI, ITALY. UCL, ACAD DEPT PSYCHIAT, MIDDLESEX HOSP, LONDON W1N 8AA, ENGLAND. UNIV IOWA HOSP & CLIN, DEPT PSYCHIAT, IOWA CITY, IA 52242 USA. RAUL CARRERA INST NEUROL RES, DEPT NEUROPSYCHIAT & NEUROPSYCHOL, RA-1428 BUENOS AIRES, DF, ARGENTINA. CHRU, SCH MED, GEN PSYCHIAT SERV, LILLE, FRANCE. BEIJING MED UNIV, INST MENTAL HLTH, BEIJING 100083, PEOPLES R CHINA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 77 TC 11 Z9 12 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD DEC PY 1996 VL 1 IS 6 BP 478 EP 491 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VZ757 UT WOS:A1996VZ75700014 PM 9154250 ER PT J AU Balajee, AS Dominguez, I Bohr, VA Natarajan, AT AF Balajee, AS Dominguez, I Bohr, VA Natarajan, AT TI Immunofluorescent analysis of the organization of telomeric DNA sequences and their involvement in chromosomal aberrations in hamster cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 26th Meeting of the European-Environmental-Mutagen-Society CY SEP 03-07, 1996 CL ROME, ITALY SP European Environm Mutagen Soc DE telomeric DNA; nuclear matrix; chromatin organization; nuclear architecture ID NUCLEAR MATRIX; CHROMATIN LOOPS; OVARY CELLS; SITES; GENES; REPLICATION; HYBRIDIZATION; REGIONS; DOMAIN; MODEL AB We have investigated the organization of telomeric (TTAGGG)(n) repeats in the extended DNA loops of chromatin of human and hamster cells by immunofluorescent technique. In humans, telomeric repeats which are predominantly localized at the termini of all the chromosomes, have been found associated with nuclear matrix. This distribution pattern did not alter, even after the removal of 90% of the DNA from the nuclear halos by EcoRI digestion. This suggests that the telomeric sequences are tightly associated with nuclear matrix and hence cannot be solubilized by nucleases. In contrast, in Chinese hamster cells (CHO B11), a major proportion of interstitial telomeric repeats are found in the loop regions, like beads on a string, with attachments to the periphery of the nuclear matrix. Unlike in human cells, EcoRI digestion removed most of the telomeric repeats from the loop regions of Chinese hamster cells. This indicates that intrachromosomal sequences are not associated with nuclear matrix, and this finding has been further substantiated by Southern hybridization of matrix associated and loop DNA fractions of hamster cells with the (TTAGGG)(n) probe. The organizational differences in the telomeric repeat sequences of Chinese hamster and human cells might be due to their chromosomal location as well as their interaction with nucleoprotein complexes specific for the termini of the eukaryotic chromosomes. Furthermore, the interstitial (TTAGGG)(n) sequences were found to be more frequently involved in the chromosomal aberrations induced by restriction enzymes. This suggests that the intrachromosomal sites of telomeric sequences behave as hot spots for DNA damage. C1 LEIDEN STATE UNIV,DEPT RADIAT GENET & CHEM MUTAGENESIS,NL-2333 AL LEIDEN,NETHERLANDS. RP Balajee, AS (reprint author), NIH,GERONTOL RES CTR,MOL GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Dominguez Garcia, Inmaculada/0000-0002-5629-0604 NR 31 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC PY 1996 VL 372 IS 2 BP 163 EP 172 DI 10.1016/S0027-5107(96)00136-4 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WE202 UT WOS:A1996WE20200003 PM 9015135 ER PT J AU Adler, ID Bishop, J Lowe, X Schmid, TE SchrieverSchwemmer, G Xu, W Wyrobek, AJ AF Adler, ID Bishop, J Lowe, X Schmid, TE SchrieverSchwemmer, G Xu, W Wyrobek, AJ TI Spontaneous rates of sex chromosomal aneuploidies in sperm and offspring of mice: A validation of the detection of aneuploid sperm by fluorescence in situ hybridization SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 26th Meeting of the European-Environmental-Mutagen-Society CY SEP 03-07, 1996 CL ROME, ITALY SP European Environm Mutagen Soc DE spontaneous aneuploidy; sperm; FISH; mouse; progeny ID INSITU HYBRIDIZATION; MOUSE; PROBES; ABNORMALITIES; LIBRARIES; NUCLEI; FISH AB This study was designed to evaluate the frequency of aneuploid sperm in young adult mice of the genotype (102/E1 X C3H/E1)F-1 determined by the fluorescence in situ hybridization (FISH) procedure and to evaluate the frequencies of aneuploid sperm observed by FISH compared with the frequencies of aneuploid offspring. Three-chromosome FISH was applied to determine the fractions of hyperhaploid and diploid sperm with DNA probes specific for chromosomes X, Y and 8. The animals were treated with three common solvents. Sperm smears were prepared for FISH by two similar protocols and were scored by different persons and in two different laboratories. There were no significant differences between scorers or laboratories. The frequencies of the sex chromosome aneuploidies in sperm (Y-Y and X-Y) were compared to the frequencies of mice carrying sex chromosome aneuploidy among controls of the heritable translocation assay in studies conducted from 1975-1995. To identify aneuploid individuals, untreated males and females of the genotype (102/E1 X C3H/E1)F-1 were mated to assess their fertility by observing three consecutive litters. Semisterile and sterile animals were further analysed by meiotic cytogenetics and by karyotyping to determine the incidence of reciprocal translocations and sex chromosome aneuploidies (XXY and XYY). Based on the analysis of 175247 sperm and 9840 progeny, the frequency of Y-Y sperm was 0.01% while 0.03% of the offspring were XYY. The frequency of X-Y sperm was 0.005% while 0.02% of the offspring were XXY. The frequencies of aneuploid sex chromosomes were not significantly different between sperm and offspring. This allows two conclusions. First, there was no detectable prenatal selection against these sex-chromosomal aneuploid offspring, and second, germ cell aneuploidy can be reliably determined in mice by sperm FISH analyses. C1 NIEHS,SYST TOXICOL LAB,RES TRIANGLE PK,NC 27709. LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94550. RP Adler, ID (reprint author), GSF FORSCHUNGSZENTRUM UMWELT & GESUNDHEIT GMBH,INST SAUGETIERGENET,NEUHERBERG,D-85764 OBERSCHLEISSHEIM,GERMANY. FU NIEHS NIH HHS [Y01-ES-10203] NR 30 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC PY 1996 VL 372 IS 2 BP 259 EP 268 DI 10.1016/S0027-5107(96)00145-5 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WE202 UT WOS:A1996WE20200012 PM 9015144 ER PT J AU Baulch, JE Lowe, XR Bishop, JB Wyrobek, AJ AF Baulch, JE Lowe, XR Bishop, JB Wyrobek, AJ TI Evidence for a parent-of-origin effect on sperm aneuploidy in mice carrying Robertsonian translocations as analyzed by fluorescence in situ hybridization SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 26th Meeting of the European-Environmental-Mutagen-Society CY SEP 03-07, 1996 CL ROME, ITALY SP European Environm Mutagen Soc DE FISH; germ cell aneuploidy; Robertsonian translocation; parent-of-origin; disomy; imprinting ID METACENTRIC CHROMOSOMES; RB(6.16) TRANSLOCATION; MOUSE; NONDISJUNCTION; SEGREGATION; DISJUNCTION; INDUCTION AB Multi-color fluorescence in situ hybridization (FISH) was employed to investigate variations in the frequency of aneuploid spermatids produced by males derived from three separate lines of Robertsonian translocations in mice: Rb(2.8)2Lub, Rb(8.12)22Lub, and Rb(8.14)16Rma, each with one arm involving chromosome 8. The DNA probes used were specific for repetitive sequences on chromosomes 8 and X. Heterozygous males for these Robertsonian translocations produced similar to 1% of spermatids with hyperhaploid for chromosome 8, which was > 80 times higher than the frequency of sperm hyperhaploid for chromosome X within the same animals; consistent elevations in chromosome-8 sperm disomy were observed among lines. In addition, similar to 25% higher fractions of sperm aneuploidy were observed when the Robertsonian translocation was inherited from the father rather than from the mother(p = 0.009). These findings illustrate the sensitivity of the FISH procedure for detecting small differences in the hyperhaploidy in male germ cells and suggest that imprinted factors may influence sperm aneuploidy. C1 LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94550. NIEHS,RES TRIANGLE PK,NC. FU NIEHS NIH HHS [Y01-ES-10203-00] NR 46 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC PY 1996 VL 372 IS 2 BP 269 EP 278 DI 10.1016/S0027-5107(96)00146-7 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WE202 UT WOS:A1996WE20200013 PM 9015145 ER PT J AU Peters, R Sikorski, RS AF Peters, R Sikorski, RS TI Nucleic acid databases on the web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 1996 VL 14 IS 13 BP 1728 EP 1728 DI 10.1038/nbt1296-1728 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VX107 UT WOS:A1996VX10700038 ER PT J AU Hacia, JG Brody, LC Chee, MS Fodor, SPA Collins, FS AF Hacia, JG Brody, LC Chee, MS Fodor, SPA Collins, FS TI Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis SO NATURE GENETICS LA English DT Article ID OVARIAN-CANCER FAMILIES; BREAST-CANCER; SUSCEPTIBILITY GENE; GERMLINE MUTATIONS; 185DELAG; LINKAGE AB The ability to scan a large gene rapidly and accurately for all possible heterozygous mutations in large numbers of patient samples will be critical for the future of medicine. We have designed high-density arrays consisting of over 96,600 oligonucleotides 20-nucleotides (nt) in length to screen for a wide range of heterozygous mutations in the 3.45-kilobases (kb) exon 11 of the hereditary breast and ovarian cancer gene BRCA1. Reference and test samples were co-hybridized to these arrays and differences in hybridization patterns quantitated by two-colour analysis. Fourteen of fifteen patient samples with known mutations were accurately diagnosed, and no false positive mutations were identified in 20 control samples. Eight single nucleotide polymorphisms were also readily detected. DNA chip-based assays may provide a valuable new technology for high-throughput cost-efficient detection of genetic alterations. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. AFFYMETRIX,SANTA CLARA,CA 95051. NR 29 TC 424 Z9 450 U1 5 U2 37 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 DEC PY 1996 VL 14 IS 4 BP 441 EP 447 DI 10.1038/ng1296-441 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VV730 UT WOS:A1996VV73000020 PM 8944024 ER PT J AU DeRisi, J Penland, L Brown, PO Bittner, ML Meltzer, PS Ray, M Chen, YD Su, YA Trent, JM AF DeRisi, J Penland, L Brown, PO Bittner, ML Meltzer, PS Ray, M Chen, YD Su, YA Trent, JM TI Use of a cDNA microarray to analyse gene expression patterns in human cancer SO NATURE GENETICS LA English DT Article ID SUPPRESSION AB The development and progression of cancer(1-3) and the experimental reversal of tumorigenicity(4,5) are accompanied by complex changes in patterns of gene expression. Microarrays of cDNA provide a powerful tool for studying these complex phenomena(6-8). The tumorigenic properties of a human melanoma cell line, UACC-903, can be suppressed by introduction of a normal human chromosome 6, resulting in a reduction of growth rate, restoration of contact inhibition, and suppression of both soft agar clonogenicity and tumorigenicity in nude mice(4,5,9). We used a high density microarray of 1,161 DNA elements to search for differences in gene expression associated with tumour suppression in this system. Fluorescent probes for hybridization were derived from two sources of cellular mRNA [UACC-903 and UACC-903(+6)] which were labelled with different fluors to provide a direct and internally controlled comparison of the mRNA levels corresponding to each arrayed gene. The fluorescence signals representing hybridization to each arrayed gene were analysed to determine the relative abundance in the two samples of mRNAs corresponding to each gene. Previously unrecognized alterations in the expression of specific genes provide leads for further investigation of the genetic basis of the tumorigenic phenotype of these cells. DNA microarrays, containing 1,161 total elements. C1 STANFORD UNIV,MED CTR,DEPT BIOCHEM,STANFORD,CA 94305. STANFORD UNIV,MED CTR,HOWARD HUGHES MED INST,STANFORD,CA 94305. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. FU FDA HHS [2T32BM07276-21]; NHGRI NIH HHS [HG00450] NR 22 TC 1491 Z9 1569 U1 9 U2 60 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 DEC PY 1996 VL 14 IS 4 BP 457 EP 460 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VV730 UT WOS:A1996VV73000022 PM 8944026 ER PT J AU DSouza, MP Harden, VA AF DSouza, MP Harden, VA TI Chemokines and HIV-1 second receptors - Confluence of two fields generates optimism in AIDS research SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8+ T-CELLS; CD26 ANTIGEN; ENVELOPE GLYCOPROTEIN; REPLICATION; FUSION; INFECTION; GENE; CD4; LYMPHOCYTES C1 NIH,HIST OFF,BETHESDA,MD 20892. NIH,DEWITT STETTEN JR MUSEUM MED RES,BETHESDA,MD 20892. RP DSouza, MP (reprint author), NIAID,DIV AIDS,PATHOGENESIS & BASIC RES BRANCH,NIH,BLDG 31,2B09,MSC 2092,BETHESDA,MD 20892, USA. NR 80 TC 263 Z9 266 U1 2 U2 5 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 DEC PY 1996 VL 2 IS 12 BP 1293 EP 1300 DI 10.1038/nm1296-1293 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VW515 UT WOS:A1996VW51500026 PM 8946819 ER PT J AU Priola, SA AF Priola, SA TI Similar protein signatures for BSE and vCjD SO NATURE MEDICINE LA English DT Editorial Material ID MICE EXPRESSING HUMAN; PRION PROTEIN; SCRAPIE; TRANSMISSION; PROPAGATION; PRP RP Priola, SA (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 11 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 DEC PY 1996 VL 2 IS 12 BP 1303 EP 1304 DI 10.1038/nm1296-1303 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VW515 UT WOS:A1996VW51500028 PM 8946821 ER PT J AU Licinio, J Wong, ML AF Licinio, J Wong, ML TI Interleukin 1 beta and fever SO NATURE MEDICINE LA English DT Editorial Material RP Licinio, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 11 TC 10 Z9 10 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 DEC PY 1996 VL 2 IS 12 BP 1314 EP 1315 DI 10.1038/nm1296-1314 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VW515 UT WOS:A1996VW51500035 PM 8946828 ER PT J AU Basile, AS Huang, JM Xie, C Webster, D Berlin, C Skolnick, P AF Basile, AS Huang, JM Xie, C Webster, D Berlin, C Skolnick, P TI N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss SO NATURE MEDICINE LA English DT Article ID NMDA-ANTAGONIST; OTOTOXIC DRUGS; RECEPTOR; COCHLEA; IFENPRODIL; EPILEPSY; NEURONS; SITE; CPP AB The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [H-3]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity. C1 LOUISIANA STATE UNIV,KRESGE HEARING RES INST S,DEPT OTORHINOLARYNGOL & BIOCOMMUN,NEW ORLEANS,LA 70112. RP Basile, AS (reprint author), NIDDKD,NEUROSCI LAB,NIH,BETHESDA,MD 20892, USA. FU NIDCD NIH HHS [T32-DC-0007] NR 39 TC 105 Z9 108 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 DEC PY 1996 VL 2 IS 12 BP 1338 EP 1343 DI 10.1038/nm1296-1338 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VW515 UT WOS:A1996VW51500039 PM 8946832 ER PT J AU Hironishi, M Kordek, R Yanagihara, R Garruto, RM AF Hironishi, M Kordek, R Yanagihara, R Garruto, RM TI Maltol (3-hydroxy-2-methyl-4-pyrone) toxicity in neuroblastoma cell lines and primary murine fetal hippocampal neuronal cultures SO NEURODEGENERATION LA English DT Article DE apoptosis; food additive; mouse; neurotoxicity; primary culture ID ALUMINUM MALTOL; APOPTOSIS; RABBITS; RAT; DISEASE; DEATH; EXPRESSION; INVITRO AB Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminium-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocampal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized in situ in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. Further toxicological investigations are warranted, since maltol is found in the daily diet of humans. (C) 1996 Academic Press Limited C1 NINCDS,LCNSS,FREDERICK CANC RES & DEV CTR,NIH,FREDERICK,MD 21702. WAKAYAMA MED COLL,DEPT ANAT & NEUROBIOL,WAKAYAMA 640,JAPAN. MED ACAD LODZ,CHAIR ONCOL,DEPT PATHOL,PL-93509 LODZ,POLAND. RI Kordek, Radzislaw/S-9616-2016 NR 29 TC 24 Z9 28 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD DEC PY 1996 VL 5 IS 4 BP 325 EP 329 DI 10.1006/neur.1996.0044 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WD131 UT WOS:A1996WD13100005 PM 9117544 ER PT J AU Rapoport, SI Hatanpaa, K Brady, DR Chandrasekaran, K AF Rapoport, SI Hatanpaa, K Brady, DR Chandrasekaran, K TI Brain energy metabolism, cognitive function and down-regulated oxidative phosphorylation in Alzheimer disease SO NEURODEGENERATION LA English DT Article DE Alzheimer disease; positron emission tomography; brain; energy metabolism; oxidative phosphorylation; mitochondria ID CYTOCHROME-OXIDASE; MITOCHONDRIAL-DNA; NEURONAL-ACTIVITY; DEMENTIA; GLUCOSE; ACTIVATION; CORTEX; TASK AB Reduced brain glucose utilization in early stages of Alzheimer disease, as measured with in vivo positron emission tomography, reflects potentially reversible down-regulation of gene expression for oxidative phosphorylation within neuronal mitochondria. Such down-regulation may occur when neuronal energy demand is first reduced by synaptic dysfunction or loss. (C) 1996 Academic Press Limited RP Rapoport, SI (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 28 TC 47 Z9 48 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD DEC PY 1996 VL 5 IS 4 BP 473 EP 476 DI 10.1006/neur.1996.0065 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WD131 UT WOS:A1996WD13100026 PM 9117565 ER PT J AU Cizza, G Brady, LS Esclapes, M Blackman, MR Gold, PW Chrousos, GP AF Cizza, G Brady, LS Esclapes, M Blackman, MR Gold, PW Chrousos, GP TI Age and gender influence basal and stress-modulated hypothalamic-pituitary-thyroidal function in Fischer 344/N rats SO NEUROENDOCRINOLOGY LA English DT Article DE thyrotropin-releasing hormone; prolactin; stress; sexual dimorphism ID CORTICOTROPIN-RELEASING HORMONE; FEMALE RATS; PARAVENTRICULAR NUCLEUS; INDUCED INHIBITION; GROWTH-HORMONE; THYROTROPIN; PROLACTIN; SECRETION; INVITRO; NEURONS AB To investigate possible gender- and age-associated changes of the hypothalamic-pituitary-thyroid (HPT) axis at baseline and during stress, we studied healthy young (3-month) and old (23-month) female 344/N Fischer rats at the basal state and after 2 h of immobilization (IMMO), in parallel to age-matched male rats. At baseline, there were no major differences of HPT axis functions between young female and male animals. Old age was associated with impaired central thyroid function in both genders, albeit to a much lesser extent in females than in males. Plasma prolactin (PRL) levels were similar in young females and males but were higher in old females than males. IMMO inhibited HPT axis functions in both genders in young, but not old animals. Thus, plasma TSH and hypothalamic TRH mRNA levels were decreased by IMMO in young, but not in old rats of both genders. IMMO increased plasma PRL in young and old males, but did not have any effect in young and old females. In summary, these data indicate that age and gender exert diverse effects on HPT axis functions at baseline and after stress. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV ENDOCRINOL & METAB,BALTIMORE,MD 21205. NR 31 TC 34 Z9 35 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1996 VL 64 IS 6 BP 440 EP 448 DI 10.1159/000127150 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA VY855 UT WOS:A1996VY85500006 PM 8990077 ER PT J AU Ogawa, S Taylor, JA Lubahn, DB Korach, KS Pfaff, DW AF Ogawa, S Taylor, JA Lubahn, DB Korach, KS Pfaff, DW TI Reversal of sex roles in genetic female mice by disruption of estrogen receptor gene SO NEUROENDOCRINOLOGY LA English DT Article DE maternal behavior; aggressive behavior; sexual behavior; lordosis; gonadal steroid receptors; transgenes ID PROGESTERONE-RECEPTOR; MOUSE-BRAIN; BEHAVIOR; RAT AB Deficiency of normal estrogen receptor (ER) gene function led to behavioral change in female mice (ERKO females). Maternal behavior as measured by retrieving of pups was reduced. In some cases, pups were killed by the ERKO females, which was not seen in wild-type animals. Aggression toward other females was increased. Female-typical lordosis behavior was reduced for at least two reasons: less response to somatosensory stimuli on the hindquarters, as well as the fact that ERKO females were immediately treated as intruder males by resident 'stud' males and were thus attacked. In sum, disruption of the ER gene led to a pattern of hormonal and neural changes which caused the females to lose their normal female-typical behavior and to behave and be treated more like males. C1 UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65201. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Ogawa, S (reprint author), ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,BOX 275,1230 YORK AVE,NEW YORK,NY 10021, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 13 TC 102 Z9 103 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1996 VL 64 IS 6 BP 467 EP 470 DI 10.1159/000127154 PG 4 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA VY855 UT WOS:A1996VY85500010 PM 8990081 ER PT J AU Duyn, JH Yang, YH Frank, JA Mattay, VS Hou, L AF Duyn, JH Yang, YH Frank, JA Mattay, VS Hou, L TI Functional magnetic resonance neuroimaging data acquisition techniques SO NEUROIMAGE LA English DT Article ID STATE FREE PRECESSION; HUMAN-BRAIN; 1.5 T; SENSORY STIMULATION; BLOOD OXYGENATION; GRADIENT ECHOES; MOTOR CORTEX; SPIN-ECHO; CONTRAST; ACTIVATION AB Functional MRI studies of human brain require rapid data acquisition techniques, to map dynamic changes with sufficient anatomical coverage. In addition, task activation studies employing functional MRI require a high scan sensitivity, in order to discriminate the small, activation-related signal changes from background noise. An overview is given of current fast scan methods, which are sensitized to detect susceptibility changes related to task-induced changes in blood oxygenation. Sources of artifacts are discussed, as well as their effect on image quality. (C) 1996 Academic Press, Inc. RP Duyn, JH (reprint author), NIH,LAB DIAGNOST RADIOL RES,OIR,BLDG 10,ROOM B1N-256,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010 NR 39 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1996 VL 4 IS 3 BP S76 EP S83 DI 10.1006/nimg.1996.0057 PN 3 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WC430 UT WOS:A1996WC43000002 PM 9345531 ER PT J AU Eden, GF VanMeter, JW Rumsey, JM Zeffiro, TA AF Eden, GF VanMeter, JW Rumsey, JM Zeffiro, TA TI The visual deficit theory of developmental dyslexia SO NEUROIMAGE LA English DT Article ID LATERAL GENICULATE-NUCLEUS; READING-DISABILITY; EYE-MOVEMENTS; RHESUS-MONKEY; NORMAL-CHILDREN; FUNCTIONAL-ORGANIZATION; CONTRAST SENSITIVITY; PHONEMIC ANALYSIS; DISABLED READERS; AREA MT AB Dyslexia is an impairment in reading that can result from an abnormal developmental process in the case of developmental dyslexia or cerebral insult in the case of acquired dyslexia, It has long been known that the clinical manifestations of developmental dyslexia are varied. In addition to their reading difficulties, individuals with developmental dyslexia exhibit impairments in their ability to process the phonological features of written or spoken language, Recently, it has been demonstrated with a variety of experimental approaches that these individuals are also impaired on a number of visual tasks involving visuomotor, visuospatial, and visual motion processing, The results of these studies, as well as the anatomical and physiological anomalies seen in the brains of individuals with dyslexia, suggest that the pathophysiology of developmental dyslexia is more complex than originally thought, extending beyond the classically defined language areas of the brain. Functional neuroimaging is a useful tool to more precisely delineate the pathophysiology of this reading disorder. C1 NIMH, SECT FUNCT BRAIN IMAGING, LPP, BETHESDA, MD 20892 USA. NIMH, CHILD PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. NIH, LAB DIAGNOST RADIOL RES, OD, BETHESDA, MD 20892 USA. SENSOR SYST INC, STERLING, VA 20164 USA. RP Eden, GF (reprint author), GEORGETOWN UNIV, MED CTR, GEORGETOWN INST COGNIT & COMPUTAT SCI, 3970 RESERVOIR RD, WASHINGTON, DC 20007 USA. NR 90 TC 38 Z9 38 U1 6 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1996 VL 4 IS 3 BP S108 EP S117 DI 10.1006/nimg.1996.0061 PN 3 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WC430 UT WOS:A1996WC43000006 PM 9345535 ER PT J AU Jezzard, P Song, AW AF Jezzard, P Song, AW TI Technical foundations and pitfalls of clinical fMRI SO NEUROIMAGE LA English DT Article ID CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; HUMAN BRAIN; TRANSVERSE RELAXATION; SENSORY STIMULATION; FUNCTIONAL MRI; SIGNAL CHANGES; CONTRAST; OXYGENATION; NMR AB Magnetic resonance imaging (MRI) has become an established and invaluable tool in the diagnosis of numerous diseases through its ability to show pathologic contrast in images of soft tissue. More recently, MRI has found application in the study of organ function, principally in the brain and heart. This article deals with MRI imaging of brain function and describes some of the techniques that allow physiological parameters such as cerebral blood volume, cerebral blood oxygenation, and cerebral perfusion to be determined. Additionally, some of the potentially confounding influences in these experiments are discussed. (C) 1996 Academic Press, Inc. RP Jezzard, P (reprint author), NIMH,UNIT MRI PHYS,LPP,NIH,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. OI Jezzard, Peter/0000-0001-7912-2251 NR 49 TC 28 Z9 28 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1996 VL 4 IS 3 BP S63 EP S75 DI 10.1006/nimg.1996.0056 PN 3 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WC430 UT WOS:A1996WC43000001 PM 9345530 ER PT J AU Weinberger, DR Mattay, V Callicott, J Kotrla, K Santha, A vanGelderen, P Duyn, J Moonen, C Frank, J AF Weinberger, DR Mattay, V Callicott, J Kotrla, K Santha, A vanGelderen, P Duyn, J Moonen, C Frank, J TI fMRI applications in schizophrenia research SO NEUROIMAGE LA English DT Article ID UNIPOLAR DEPRESSION; CORTEX; MRI AB fMRI has unique potential in the study of psychiatric patients, particularly in characterizing individual variations and changes over time. We have performed four studies of patients with schizophrenia, using three different fMRI acquisition protocols: (1) 3-D echo-shifted FLASH, a multishot volumetric approach; (2) 3-D PRESTO, a hybid of multishot and echo-planar imaging (EPI) methods that also acquires true volumetric data; and (3) a whole-brain isotropic, multislice EPI technique. Patients were studied during sensorimotor activation and during a novel ''N back'' working memory paradigm. In general, patients show normal sensorimotor activation responses, although motor cortical activation tends to be less completely lateralized. Prefrontal activation during working memory tends to be reduced in patients with schizophrenia even when performance is normal. A major potential confound in studying this patient population with fMRI is the effect of motion. We propose several methodological standards to address this problem, including comparisons of motion corrections parameters, voxel variances, and the use of an ''internal activation standard.'' (C) 1996 Academic Press, Inc. C1 BAYLOR COLL MED,HOUSTON,TX 77030. NIH,IN VIVO NMR CTR,NCRR,BETHESDA,MD 20892. NIH,LAB DIAGNOST & RADIOL RES,OD,BETHESDA,MD 20892. RP Weinberger, DR (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NIH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. RI Callicott, Joseph/C-9102-2009; Moonen, Chrit/K-4434-2016 OI Callicott, Joseph/0000-0003-1298-3334; Moonen, Chrit/0000-0001-5593-3121 NR 29 TC 37 Z9 37 U1 2 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1996 VL 4 IS 3 BP S118 EP S126 DI 10.1006/nimg.1996.0062 PN 3 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WC430 UT WOS:A1996WC43000007 PM 9345536 ER PT J AU Zeffiro, T AF Zeffiro, T TI Clinical functional image analysis: Artifact detection and reduction SO NEUROIMAGE LA English DT Article ID AUTOMATED ALGORITHM; SURFACE; REGISTRATION; MRI AB Rapid improvements in functional magnetic resonance neuroimaging technology have resulted in impressive advances in our understanding of structure/function relationships in the human brain. The application of this new technology to the understanding of human brain disease is currently limited by difficulties in extracting task-related signal change from signal intensity time series that have been contaminated by artifacts arising from various intrinsic and extrinsic sources. Effects induced by interscan head motion are a major source of these artifacts. The correction of these artifacts by registration of pairs of reconstructed images has been a focus of research for the past few years and there are now a number of effective means to compensate for this source of noise. This paper discusses issues concerning the prevention and correction of interscan head motion as well as other sources of error variation in fMRI time series. (C) 1996 Academic Press, Inc. C1 NIH,LAB DIAGNOST RADIOL RES,OIR,OD,BETHESDA,MD 20892. RP Zeffiro, T (reprint author), SENSOR SYST INC,STERLING,VA 20164, USA. NR 16 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1996 VL 4 IS 3 BP S95 EP S100 DI 10.1006/nimg.1996.0059 PN 3 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WC430 UT WOS:A1996WC43000004 PM 9345533 ER PT J AU Samii, A Wassermann, EM Ikoma, K Mercuri, B George, MS OFallon, A Dale, JK Straus, SE Hallett, M AF Samii, A Wassermann, EM Ikoma, K Mercuri, B George, MS OFallon, A Dale, JK Straus, SE Hallett, M TI Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression SO NEUROLOGY LA English DT Article ID LONG-TERM POTENTIATION; TRANSCRANIAL MAGNETIC STIMULATION; CORTEX; PERFORMANCE; RESPONSES; HIPPOCAMPUS; PLASTICITY; DEFINITION; DISEASE AB We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force. MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal. The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects. C1 NINCDS, NIH, HUMAN MOTOR CONTROL SECT, BETHESDA, MD 20892 USA. NINCDS, NIH, MED NEUROL BRANCH, BETHESDA, MD 20892 USA. NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. NIAID, CLIN INVEST LAB, NIH, BETHESDA, MD 20892 USA. RI Ikoma, Katsunori/D-8158-2012 NR 43 TC 73 Z9 74 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1996 VL 47 IS 6 BP 1410 EP 1414 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA VX507 UT WOS:A1996VX50700011 PM 8960719 ER PT J AU Castellanos, FX Giedd, JN Hamburger, SD Marsh, WL Rapoport, JL AF Castellanos, FX Giedd, JN Hamburger, SD Marsh, WL Rapoport, JL TI Brain morphometry in Tourette's syndrome: The influence of comorbid attention-deficit/hyperactivity disorder SO NEUROLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; BASAL GANGLIA; MRI AB Three separate groups, using MRI, have reported basal ganglia abnormalities in Tourette's syndrome (TS). We found similar abnormalities in boys with attention-deficit/hyperactivity disorder (ADHD). Because TS and ADHD are frequently comorbid, we contrasted ADHD boys with and without TS along with control subjects. As expected, we found a significant loss of the normal globus pallidus asymmetry in the patients, but presence or absence of TS did not differentiate the ADHD groups. We conclude that accounting for ADHD comorbidity will be important in future TS morphometric studies. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 10 TC 53 Z9 56 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1996 VL 47 IS 6 BP 1581 EP 1583 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA VX507 UT WOS:A1996VX50700043 PM 8960751 ER PT J AU Mullol, J Baraniuk, JN Logun, C Benfield, T Picado, C Shelhamer, JH AF Mullol, J Baraniuk, JN Logun, C Benfield, T Picado, C Shelhamer, JH TI Endothelin-1 induces CM-CSF, IL-6 and IL-8 but not G-CSF release from a human bronchial epithelial cell line (BEAS-2B) SO NEUROPEPTIDES LA English DT Article ID SMOOTH-MUSCLE CELLS; HUMAN NASAL-MUCOSA; VASOCONSTRICTOR PEPTIDE; INFLAMMATORY CYTOKINES; AIRWAY EPITHELIUM; EXPRESSION; INTERLEUKIN-8; RECEPTOR; GENES; VIRUS AB Endothelin (ET) is a powerful vasoconstrictor and bronchoconstrictor peptide that may be involved in the pathogenesis of bronchial asthma. We have investigated the effect of ET on the secretion of IL-6, IL-8, GM-CSF and G-CSF in a bronchial epithelial cell line (BEAS-2B), Incubation of BEAS-2B cells with ET-I (10(-13) to 10(-7) M) for 4 h caused dose-related increases in the release of IL-8 (68% increase above control, P < 0.001) and IL-6 (43% increase above control, P < 0.001), compared to untreated control cells. After 48 h incubation, ET-1 also increased the release of IL-8 by 35% (P < 0.001) and GM-CSF by 38% (P < 0.01). ET-1 had no significant effect on G-CSF release. ET-1 did not induce cell proliferation at 24 or 48 h. Since ET-immunoreactive materials are expressed in epithelial cells in asthma, it is possible that ET-1 of epithelial origin may act in a paracrine or autocrine fashion on airway epithelial ET receptors to stimulate IL-8, IL-N6 and GM-CSF release, Thus, ET-1 may play a role in the regulation of the cytokine responses involved in inflammation of the airway mucosa. C1 NIH,DEPT CRIT CARE MED,CTR CLIN,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT MED,WASHINGTON,DC. HOSP CLIN & UNIV BARCELONA,DEPT MED,FUNDACIO CLIN,SERV PNEUMOL & ALLERGIA RESP,BARCELONA,SPAIN. NR 36 TC 34 Z9 35 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD DEC PY 1996 VL 30 IS 6 BP 551 EP 556 DI 10.1016/S0143-4179(96)90038-4 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA WB712 UT WOS:A1996WB71200007 PM 9004253 ER PT J AU Jeng, YJ Lolait, SJ Strakova, Z Chen, C Copland, JA Mellman, D Hellmich, MR Soloff, MS AF Jeng, YJ Lolait, SJ Strakova, Z Chen, C Copland, JA Mellman, D Hellmich, MR Soloff, MS TI Molecular cloning and functional characterization of the oxytocin receptor from a rat pancreatic cell line (RINm5F) SO NEUROPEPTIDES LA English DT Article ID PROTEIN-KINASE-C; MAMMARY-GLAND; ARGININE-VASOPRESSIN; SIGNAL-TRANSDUCTION; OVINE ENDOMETRIUM; INSULIN RELEASE; NORMAL MOUSE; FREE CALCIUM; EXPRESSION; GENE AB Oxytocin (OT) and vasopressin (AVP) stimulate insulin and glucagon release from the pancreas, and evoke insulin secretion from the rat insulinoma cell line, RINm5F. To determine which AVP/OT receptor subtype is expressed in RINm5F cells, we used PCR with degenerate primers to two transmembrane domains of the AVP (Via, V1b (or V3), V2) and OT receptors (OTRs). The single PCR fragment identified was used to obtain a full length cDNA from a RINm5F cDNA library. Comparison of the deduced amino acid sequence of this clone with uterine OTR sequences from several species (human, sheep, bovine) and to the pig kidney epithelial cell (LLC-PK1) OTR reveals a very high degree of homology. After the RIN cell OTR cDNA was stably transfected into CHO cells (CHO-OTR), the cell membranes bound iodinated oxytocin antagonist with an apparent K-d comparable to that of RIN cell membranes and those from other OT target cells. Comparison of the ligand specificities of CHO-OTR and RIN cells membranes showed that the relative K-i values of a series of OT analogues were approximately equivalent in both preparations. The rank order of apparent K-i values also corresponded to published values for the rat myometrium, where OT elicits intracellular calcium transients, and increases inositol phosphate production. In uterine endometrium and amnion cells, OT stimulates prostaglandin release. Stimulation of CHO-OTR cells with OT caused an increase in cytosolic calcium concentration originating from both intracellular and extracellular sources, and a dose-dependent increase in inositol phosphate levels. Arachidonic acid release and PGE, synthesis were also stimulated by OT These findings (amino acid sequence homology, binding specificity, and signal transduction/second messenger production) suggest that OTRs from RINm5F cells are indistinguishable from OTRs that have been described in other tissues. The expression of OTR in pancreatic cells implies that OT plays a role in pancreatic function. C1 UNIV TEXAS,MED BRANCH,DEPT OBSTET & GYNECOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT SURG,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,SEALY CTR MOL SCI,GALVESTON,TX 77555. NIMH,LAB CELLULAR & MOL REGULAT,BETHESDA,MD 20892. FU NICHD NIH HHS [HD08406] NR 46 TC 26 Z9 27 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD DEC PY 1996 VL 30 IS 6 BP 557 EP 565 DI 10.1016/S0143-4179(96)90039-6 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA WB712 UT WOS:A1996WB71200008 PM 9004255 ER PT J AU Mann, JJ Malone, KM Sweeney, JA Brown, RP Linnoila, M Stanley, B Stanley, M AF Mann, JJ Malone, KM Sweeney, JA Brown, RP Linnoila, M Stanley, B Stanley, M TI Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; depression; suicide; CSF amine metabolites ID CSF MONOAMINE METABOLITES; IMPULSIVE FIRE SETTERS; 5-HYDROXYINDOLEACETIC ACID; SCHIZOPHRENIC-PATIENTS; AFFECTIVE-DISORDERS; BINDING-SITES; HOMOVANILLIC-ACID; VIOLENT OFFENDERS; SYMPTOM PATTERNS; FRONTAL-CORTEX AB Background: Serotonin abnormalities have been reported in the brain of suicide victims. Evidence of a serotonin deficiency in suicide attempters is less consistent. We hypothesized that a serotonin deficiency may be present in suicide attempters whose attempt behavior more closely approximates completed suicide. Method: Sixty-seven (67) drug-free depressed inpatients (46 suicide attempters, 21 nonattempters) underwent research clinical assessments and a lumbar puncture. Cerebrospinal fluid (CSF) monoamine metabolites were assayed. Degree of medical damage and intent of the most recent suicide attempt were rated. Results: CSF amine metabolites did not differentiate suicide attempters as a group from nonattempters. However, reduced serotonergic activity, as indicated by lower levels of CSF 5-hydroxyindoleacetic acid [5-HIAA] was associated with a history of planned suicide attempts and with suicide attempts that resulted in greater medical damage. Other monoamine metabolites did not correlate with seriousness of suicidal behavior, except for low CSF homovanillic acid and higher medical damage. No correlation was found with violent method. Conclusions: Planned and more medically damaging suicide attempts appear to be associated specifically with low serotonergic activity and, therefore, resemble completed suicide both behaviorally and biochemically. It remains to be determined whether low levels of CSF 5-HIAA can predict greater medical damage in future suicide attempts. (C) 1996 American College of Neuropsychopharmacology C1 UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. NIAAA,CLIN STUDIES LAB,ROCKVILLE,MD 20852. RP Mann, JJ (reprint author), COLUMBIA UNIV COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,DEPT PSYCHIAT,NEW YORK,NY 10032, USA. RI Stanley, Barbara/J-8736-2013 FU NIMH NIH HHS [MH40048, MH48514, MH46745] NR 77 TC 97 Z9 103 U1 2 U2 5 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 DEC PY 1996 VL 15 IS 6 BP 576 EP 586 DI 10.1016/S0893-133X(96)00102-9 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VU943 UT WOS:A1996VU94300006 PM 8946432 ER PT J AU Jucker, M DAmato, F Mondadori, C Mohajeri, H Magyar, J Bartsch, U Schachner, M AF Jucker, M DAmato, F Mondadori, C Mohajeri, H Magyar, J Bartsch, U Schachner, M TI Expression of the neural adhesion molecule L1 in the deafferented dentate gyrus SO NEUROSCIENCE LA English DT Article DE cell adhesion molecule; sprouting; synaptogenesis; hippocampus; septohippocampal cholinergic system; entorhinal cortex lesions ID ENTORHINAL CORTEX LESIONS; IMMUNOELECTRON MICROSCOPIC LOCALIZATION; FIBRILLARY ACIDIC PROTEIN; 2ND MESSENGER SYSTEMS; CELL-ADHESION; N-CAM; NEURITE OUTGROWTH; ADULT-RAT; IMMUNOGLOBULIN SUPERFAMILY; REACTIVE SYNAPTOGENESIS AB Expression of the neural adhesion molecule L1 and its potential involvement in axonal sprouting were examined in the deafferented rat dentate gyrus. We focused on the dentate gyrus because of its well-defined cytoarchitecture and well-characterized neuronal degeneration and sprouting response following entorhinal cortex lesions. In the molecular layer of the dentate gyrus, a trilaminar staining pattern was observed, with the middle molecular layer exhibiting slightly denser immunolabeling compared to both inner and outer molecular layers. Two to 12 days after a unilateral entorhinal cortex lesion, a progressive loss of L1 immunolabeling was noted in the ipsilateral middle and outer molecular layers, followed by a substantial reappearance of immunostaining 65 days after lesion incidence. The width of the immunostained ipsilateral inner molecular layer revealed a progressive widening and by postlesion day 65 occupied about 50% of the total width of the molecular layer. Immunoelectron microscopy localized L1 to the surface of unmyelinated axons in both normal and deafferented dentate gyrus. In situ hybridization revealed LI messenger RNA confined to neurons throughout the hippocampal formation, but did not indicate changes in L1 messenger RNA levels in the hippocampus, dentate gyrus, entorhinal cortex or basal forebrain in response to unilateral entorhinal cortex lesions. Changes in L1 immunolabeling in the deafferented dentate gyrus corresponded in a spatial and temporal manner to changes of the synaptic marker synaptophysin and axonal marker phosphorylated tau. Results of the present study are most consistent with the view that L1 is expressed on reinnervating fibers after they make synaptic contacts with other structures. Thus, L1 appears to be involved in the maturation and stabilization of reinnervating fibers and consequently may play an important role in the repair process of the lesioned adult CNS. Copyright (C) 1996 IBRO. C1 SWISS FED INST TECHNOL,DEPT NEUROBIOL,ZURICH,SWITZERLAND. CIBA GEIGY LTD,DIV PHARMACEUT RES,BASEL,SWITZERLAND. RP Jucker, M (reprint author), NIA,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 61 TC 36 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1996 VL 75 IS 3 BP 703 EP 715 DI 10.1016/0306-4522(96)00276-X PG 13 WC Neurosciences SC Neurosciences & Neurology GA VU268 UT WOS:A1996VU26800006 PM 8951867 ER PT J AU Huang, KX Walters, JR AF Huang, KX Walters, JR TI Dopaminergic regulation of AP-1 transcription factor DNA binding activity in rat striatum SO NEUROSCIENCE LA English DT Review DE 6-hydroxydopamine; reserpine; nigrostriatal; SKF 38393; Parkinsonism; immediate early gene ID IMMEDIATE-EARLY GENES; C-FOS EXPRESSION; RECEPTOR MESSENGER-RNA; SUBSTANTIA-NIGRA; NUCLEUS-ACCUMBENS; BASAL GANGLIA; STRIATOPALLIDAL NEURONS; ANTAGONIST MK-801; RESPONSE-ELEMENT; PROMOTER REGION AB Dopaminergic modulation of the DNA binding activity of AP-1, Sp1, CREB and AP-2 transcription factors was examined in rat striatal nuclear extracts by gel shift assay. AP-1 binding was selectively increased in the striatum following depletion of dopamine by 6-hydroxydopamine-induced lesion of the nigrostriatal pathway or after reserpine treatment. The D-1 agonist SKF 38393 dose-dependently increased AP-1 binding; this effect was significantly increased in reserpine-treated rats and even more markedly enhanced in denervated striatum. The D-2/D-3 agonist quinpirole, administered alone, did not affect striatal activator protein-1 binding; in combination, quinpirole and SKF 38393 acted synergistically in normal and reserpine-treated rats but not in 6-hydroxydopamine-lesioned rats, suggesting that mechanisms underlying D-1-D-2/D-3 interactions are altered after dopamine denervation. Most, but not all, of the changes in AP-1 binding activity observed in this study are consistent with changes in levels of Fos/Jun family proteins observed after similar treatments. These results support the hypothesis that D-1 receptor stimulation activates striatonigral neurons and modulates expression of AP-1-related genes in these neurons, while D-2 receptor stimulation mediates tonic inhibition of AP-1 expression and activity in the striatopallidal neurons. Moreover, the findings provide evidence that the loss of dopaminergic input to the striatum, as occurs in Parkinson's disease, induces long-lasting alterations in the regulation of striatal gene expression which may contribute to the disease's progress. C1 NINCDS,EXPT THERAPEUT BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 135 TC 19 Z9 19 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1996 VL 75 IS 3 BP 757 EP 775 DI 10.1016/0306-4522(96)00229-1 PG 19 WC Neurosciences SC Neurosciences & Neurology GA VU268 UT WOS:A1996VU26800010 PM 8951871 ER PT J AU Voorn, P Brady, LS Berendse, HW Richfield, EK AF Voorn, P Brady, LS Berendse, HW Richfield, EK TI Densitometrical analysis of opioid receptor ligand binding in the human striatum .1. Distribution of mu opioid receptor defines shell and core of the ventral striatum SO NEUROSCIENCE LA English DT Article DE basal ganglia; nucleus accumbens; receptor autoradiography; kappa opioid receptor; dopamine D-1 receptor ID RAT NUCLEUS-ACCUMBENS; SENSITIVE ADENYLATE-CYCLASE; IN-SITU HYBRIDIZATION; FREELY MOVING RATS; BASAL GANGLIA; OPIATE RECEPTORS; DOPAMINE RELEASE; AUTORADIOGRAPHIC LOCALIZATION; PRESYNAPTIC INHIBITION; MESSENGER-RNA AB Changes in opioid neurotransmission have been implicated in several basal ganglia-related neurological and psychiatric disorders. To gain a better insight into the opioid receptor distribution in the normal human striatum, we examined in post mortem brain the distribution of the mu opioid receptor using ligand binding of [H-3]D-ala(2)-N-methyl-phe(4), gly-ol(5)-enkephalin. Our results indicate at the regional level the presence of a dorsal-to-ventral high-to-low density gradient in the striatum, with lowest densities in the ventral one-third of the putamen and in the nucleus accumbens. At the subregional level, the nucleus accumbens shows two major types of heterogeneities. First, low vs intermediate binding densities distinguish the core and shell subdivisions, respectively. The low-density core and intermediate-density shell regions extend into the putamen and are therefore characteristic for the entire ventral striatum. The second type of heterogeneity is formed by small areas located along the ventral contours of the nucleus accumbens and putamen that display the highest binding density of the entire striatum. Since these areas can also be recognized in the distribution patterns of other markers and in the cytoarchitecture, they appear to possess a separate identity. To emphasize their special neurochemical characteristics we propose the description ''neurochemically unique domains in the accumbens and putamen''. The present results, with the difference between core and shell of the ventral striatum as the most prominent outcome, together with the notion that the connectional relationships and neurochemical organization of the striatum are very heterogeneous, suggest a strong regional functional differentiation for mu receptor function in the human striatum. Copyright (C) 1996 IBRO. C1 FREE UNIV AMSTERDAM,NEUROSCI RES INST,DEPT ANAT & EMBRYOL,NL-1081 BT AMSTERDAM,NETHERLANDS. NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. FREE UNIV AMSTERDAM,ACAD HOSP,DEPT NEUROL,NL-1081 HV AMSTERDAM,NETHERLANDS. UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,DIV NEUROPATHOL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PHARMACOL,DIV NEUROPATHOL,ROCHESTER,NY 14642. FU NIMH NIH HHS [MH 40381] NR 78 TC 47 Z9 47 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1996 VL 75 IS 3 BP 777 EP 792 DI 10.1016/0306-4522(96)00271-0 PG 16 WC Neurosciences SC Neurosciences & Neurology GA VU268 UT WOS:A1996VU26800011 PM 8951872 ER PT J AU Gauda, EB Bamford, O Gerfen, CR AF Gauda, EB Bamford, O Gerfen, CR TI Developmental expression of tyrosine hydroxylase, D-2-dopamine receptor and substance P genes in the carotid body of the rat SO NEUROSCIENCE LA English DT Article DE arterial chemoreceptors; glomus cells ID MESSENGER-RNA; NEUROKININ-A; DOPAMINE; HYPOXIA; CAT; INVITRO; BODIES AB Alterations in the level of putative neurotransmitters/neuromodulators and corresponding receptors may be a possible mechanism involved in changes in chemosensitivity of peripheral chemoreceptors in the carotid body during development. Using quantitative in situ hybridization histochemistry, levels of messenger RNAs encoding tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, the D-2-dopamine receptor and substance P of newborn rats at postnatal days 0, 2, 14 and 21 were determined. For comparison, during the same time points during development, we also determined the level of expression of these messenger RNAs in the cells of the superior cervical ganglion which are not chemosensitive. Tyrosine hydroxylase and D-2-dopamine receptor messenger RNAs were co-localized in many of the cells in both the carotid body and the superior cervical ganglion. In the carotid body, the level of tyrosine hydroxylase messenger RNA expression was greatest at birth, significantly decreased by 48 h postnatal age and remained decreased at 14 and 21 postnatal days. In contrast, D-2-dopamine receptor messenger RNA levels significantly increased with postnatal age in the carotid body. This profile of an inverse relationship between the level of expression of the messenger RNAs for tyrosine hydroxylase and D2-dopamine receptor was not observed in the superior cervical ganglion where tyrosine hydroxylase and D-2-dopamine receptor messenger RNAs levels did not significantly change from postnatal days 0 to 21. Lastly, in the rat carotid body, substance P messenger RNA was not detected. However, substance P messenger RNA was abundant in the nodose and petrosal ganglion. The increasing contribution of carotid body on ventilation with increasing postnatal age is associated with changes in levels of gene expression for tryosine hydroxylase and D-2-dopamine receptor in the carotid body. Copyright (C) 1996 IBRO. C1 NIMH, NEUROPHYSIOL LAB, BETHESDA, MD 20892 USA. RP Gauda, EB (reprint author), JOHNS HOPKINS MED INST, DEPT PEDIAT, BALTIMORE, MD 21287 USA. NR 33 TC 36 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1996 VL 75 IS 3 BP 969 EP 977 DI 10.1016/0306-4522(96)00312-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VU268 UT WOS:A1996VU26800027 PM 8951888 ER PT J AU Sauer, B AF Sauer, B TI Multiplex Cre/lox recombination permits selective site-specific DNA targeting to both a natural and an engineered site in the yeast genome SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CRE RECOMBINASE; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; MAMMALIAN-CELLS; TRANSGENIC MICE; GENE; SYSTEM; LOXP; BACTERIOPHAGE-P1; CHROMOSOME AB Variant lex sites having an altered spacer region (heterospecific lex sites) are not proficient for Cre-mediated recombination with the canonical 34 bp loxP site, but can recombine with each other. By placing different heterospecific lex sites at different genomic locations, Cre can catalyze independent DNA recombination events at multiple loci in the same cell without concern that unwanted inter-locus recombination events will be generated, Such heterospecific lex sites also allow Cre to specifically target efficient integration of exogenous DNA to endogenous lex-like sequences that naturally occur in the genome, Specific targeting occurs only with a DNA vector carrying a heterospecific lex site in which the spacer region has been redesigned to match the 'spacer' region of the targeted chromosomal element, Moreover, in cells expressing a catalytically active Cre recombinase, naturally occurring lex-like sequences can exhibit almost 20% mitotic recombination, Thus, in the same cell, heterospecific lex sites can be used independently at multiple loci for integration, for deletion and for enhanced mitotic recombination, thereby increasing the repertoire of genomic manipulations catalyzed by the Cre recombinase. RP Sauer, B (reprint author), NIDDKD,NIH,BETHESDA,MD 20892, USA. NR 41 TC 61 Z9 62 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 1996 VL 24 IS 23 BP 4608 EP 4613 DI 10.1093/nar/24.23.4608 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY198 UT WOS:A1996VY19800002 PM 8972844 ER PT J AU Lichy, JH Majidi, M Elbaum, J Tsai, MM AF Lichy, JH Majidi, M Elbaum, J Tsai, MM TI Differential expression of the human ST5 gene in HeLa-fibroblast hybrid cell lines mediated by YY1 evidence that YY1: Plays a part in tumor suppression SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CERVICAL-CARCINOMA CELLS; TRANSCRIPTIONAL REPRESSION; HUMAN CHROMOSOME-11; HUMAN KERATINOCYTES; ADENOVIRUS E1A; DNA; PROTEIN; RELIEF; IDENTIFICATION; PROMOTER AB Through a mutational analysis of a differentially regulated enhancer, we present evidence that supports a role for the transcription factor YY1 in tumor suppression in HeLa/fibroblast somatic cell hybrids, The human ST5 gene was previously shown to be expressed as three RNA species, 4.6, 3.1 and 2.8 kb in length, Whereas the two larger species are expressed at similar levels in all cell lines examined, the 2.8 kb mRNA is expressed specifically in non-tumorigenic hybrids, In this study, the basis for the differential expression of this mRNA species was investigated, The message was shown to originate from a promoter located within an intron of the ST5 gene, An enhancer located similar to 1500 nt upstream of the start site was required for cell type specific expression, Mutational analysis of this enhancer revealed an AP1 site and five YY1 sites which were necessary for full enhancer activity, Levels of YY1 DNA binding activity were found to be as much as 6-fold higher in the non-tumorigenic cells relative to the tumorigenic cells, while AP1 activity was similar in both cell types, These results suggest that a signaling pathway targeting YY1 may play an important role in tumor suppression in HeLa-fibroblast hybrids. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RP Lichy, JH (reprint author), ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,14 ST & ALASKA AVE NW,WASHINGTON,DC 20306, USA. FU NCI NIH HHS [R01CA-64114] NR 30 TC 16 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 1996 VL 24 IS 23 BP 4700 EP 4708 DI 10.1093/nar/24.23.4700 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY198 UT WOS:A1996VY19800014 PM 8972856 ER PT J AU Gumowski, J Loughran, M AF Gumowski, J Loughran, M TI Diseases of the adrenal gland SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID CUSHINGS-SYNDROME; DIAGNOSIS; PHEOCHROMOCYTOMA; THERAPY AB Diseases of the adrenal gland are rare but potentially lethal. The adrenal cortex and the adrenal medulla function quite differently and independent of each other. Diseases of both hyperfunction as well as hypofunction will be reviewed. Astute nursing assessment and patient education in adrenal signs and symptoms are essential in the management of these diseases. A detailed case study illustrates three diseases of the adrenal gland. C1 NATL INST HLTH,CTR CLIN,DEPT NURSING,BETHESDA,MD. NR 32 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD DEC PY 1996 VL 31 IS 4 BP 747 EP & PG 23 WC Nursing SC Nursing GA VY230 UT WOS:A1996VY23000007 PM 8969336 ER PT J AU Hill, HA Eley, JW Harlan, LC Greenberg, RS Barrett, RJ Chen, VW AF Hill, HA Eley, JW Harlan, LC Greenberg, RS Barrett, RJ Chen, VW TI Racial differences in endometrial cancer survival: The black/white cancer survival study SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BLACK PATIENTS; CARCINOMA; WOMEN; STAGE AB Objective: To identify factors that explain a lower survival rate among black women with endometrial cancer when compared to white women. Methods: Data are from the National Cancer Institute's Black/White Cancer Survival Study, a population-based study of racial differences in cancer survival. Subjects included 329 white and 130 black women, ages 20-79 years, residing in the metropolitan areas of Atlanta, New Orleans, or San Francisco-Oakland, diagnosed with endometrial cancer from 1985 to 1987. Known prognostic factors were assessed as potential explanatory variables for the black-white survival difference using proportional hazards regression. Information was derived from interviews, abstracts of hospital and physicians' records, and a centralized review of biopsy and surgical specimens. Results: Adjusting for age and geographic location, risk of death among black women was 4.0 times (95% confidence interval [CI] 2.8, 5.6) that of white women. Approximately 40% of this difference could be attributed to a more advanced stage at diagnosis among black women, and 23% to tumor characteristics and treatment. Further adjustment for all remaining factors reduced the hazard ratio to 1.6 (95% CI 1.0, 2.6). Conclusion: Eighty percent of the excess mortality among black women is explained by racial differences in stage at diagnosis, tumor characteristics, treatment, sociodemographic characteristics, hormonal and reproductive factors, and factors related to comorbidities and health behavior. Difference in stage at diagnosis is prominent in explaining the disparity in endometrial cancer survival rates in black and white women. Potential differences in treatment within stage merit further exploration. Copyright (C) 1996 by The American College of Obstetricians and Gynecologists. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. RP Hill, HA (reprint author), EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,1518 CLIFTON RD NE,ATLANTA,GA 30322, USA. FU NCI NIH HHS [N01-CN-25501, N01-CN-45174, N01-CN-35043] NR 19 TC 52 Z9 52 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1996 VL 88 IS 6 BP 919 EP 926 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VU946 UT WOS:A1996VU94600003 PM 8942828 ER PT J AU Yoon, BH Jun, JK Park, KH Syn, HC Gomez, R Romero, R AF Yoon, BH Jun, JK Park, KH Syn, HC Gomez, R Romero, R TI Serum C-reactive protein, white blood cell count, and amniotic fluid white blood cell count in women with preterm premature rupture of membranes SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HISTOLOGIC CHORIOAMNIONITIS; GRAM STAIN; MICROBIAL INVASION; INFECTION; LABOR; AMNIOCENTESIS; INTERLEUKIN-6; PREDICTOR; DIAGNOSIS; MORBIDITY AB Objective: To compare the diagnostic performance of maternal blood C-reactive protein, white blood cell count (WBC), and amniotic fluid (AF) WBC in the identification of positive AF culture, histologic and clinical chorioamnionitis, and neonatal morbidity in women with preterm premature rupture of membranes (PROM). Methods: Maternal blood was collected for the determination of C-reactive protein and WBC al the time of amniocentesis from 90 women with preterm PROM. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. Amniotic fluid WBC was determined for research purposes. Receiver operating characteristic curve and logistic regression were used for statistical analysis. Results: The prevalence of positive AF culture was 28% (25 of 90). Women with positive AF culture and clinical chorioamnionitis had significantly higher median C-reactive protein, WBC, and AF WBC than did women without these conditions (P < .05), whereas women with histologic chorioamnionitis and significant neonatal morbidity had higher median C-reactive protein and AF WBC, but not WBC, than those without the conditions (P < .05). An AF WBC of at least 20 cells per mm(3) had a greater sensitivity than C-reactive protein (cutoff, 0.7 mg/dL) and WBC (cutoff, 13,000 cells per mm(3)) in the detection of positive AF culture and histologic chorioamnionitis. Logistic regression analysis indicated that among AF WBC, C-reactive protein, and WBC, AF WBC was the best predictor of positive AF culture (odds ratio [OR]: 24.2 95% confidence interval [CI] 6.0, 97.5, P < .001), histologic (OR 74.0, 95% CI 7.4, 736.3, P < .001) and clinical chorioamnionitis (OR 8.9, 95% CI 0.9, 85.6, P = .057), and neonatal morbidity (OR 4.3, 95% CI 1.1, 16.6, P < .05). Conclusion: Amniotic fluid WBC performs better than C-reactive protein and maternal blood WBC in the diagnosis of positive AF culture, histologic and clinical chorioamnionitis, and neonatal morbidity in women with preterm PROM. (Copyright (C) 1996 by The American College of Obstetricians and Gynecologists.) C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RP Yoon, BH (reprint author), SEOUL NATL UNIV,COLL MED,DEPT OBSTET & GYNECOL,CHONGNO KU,28 YUNGUN DONG,SEOUL 110744,SOUTH KOREA. RI Yoon, Bo Hyun/H-6344-2011; Jun, Jong Kwan/D-5776-2012 OI Jun, Jong Kwan/0000-0002-0242-1736 NR 23 TC 83 Z9 86 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1996 VL 88 IS 6 BP 1034 EP 1040 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VU946 UT WOS:A1996VU94600024 PM 8942849 ER PT J AU Chan, CC Factor, V Li, Q Nagy, P Peng, B Thorgeirsson, SS AF Chan, CC Factor, V Li, Q Nagy, P Peng, B Thorgeirsson, SS TI The eyes of transforming growth factor-beta 1 (TGF-beta 1) transgenic mice - Morphology and the development of endotoxin-induced uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE transforming growth factor-beta I (TGF-beta I); transgenic mouse; cataract; retinal edema; endotoxin-induced uveitis (EIU) ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; FACTOR-BETA; MESSENGER-RNA; AQUEOUS-HUMOR; GROWTH-FACTOR-BETA-1; EXPRESSION; CYTOKINE; INDUCTION; RAT AB Transforming growth factor-beta (TGF beta) is a potent regulator of cellular growth and immune function. The authors studied ocular histology and endotoxin-induced uveitis in a TGF-beta 1 transgenic (Tg) murine model. TGF-beta 1 Tg mice were generated by micro injecting a gene constructed by fusing the mouse albumin enhancer/promoter and porcine TGF-beta 1 cDNA. The eyes of Tg mice from two to 14 weeks of age were studied histologically. Tg mice, two to five weeks of age exhibited mild fragmentation of the lens fibers and retinal edema. No pathology was found from six to ten weeks of age, however, a progressive increased frequency of cataract was observed from 11 to 14 weeks of age. Plasma TGF-beta 1 levels were much higher in Tg mice than age-matched wild type control littermates (wt). Endotoxin-induced uveitis (EIU) in six- to eight-week-old Tg and wt mice was induced by footpad injection of lipopolysaccharide (LPS). Mice were euthanized 24 hr after LPS injection, the eyes were collected for histology and serum assayed for IL-6 and TGF-beta 1. There was a decrease in the mean numbers of infiltrating cells in Tg mice compared to wt mice. Serum IL-6 and TGF-beta 1 were much higher in Tg mice. The authors concluded that expression of the TGF-beta 1 transgene in the eyes may have effect on lens growth. Overexpression of TGF-beta 1 results in little or no effect on the development of EIU. C1 NCI,EXPT CARCINOGENESIS LAB,NCI,BETHESDA,MD 20892. RP Chan, CC (reprint author), NEI,IMMUNOL LAB,NCI,10 CTR DR MSC 1858,BETHESDA,MD 20892, USA. NR 35 TC 2 Z9 2 U1 0 U2 1 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD DEC PY 1996 VL 4 IS 4 BP 183 EP 191 DI 10.3109/09273949609079651 PG 9 WC Ophthalmology SC Ophthalmology GA WG045 UT WOS:A1996WG04500002 PM 22827457 ER PT J AU Dougherty, ER Zhang, YQ Chen, YD AF Dougherty, ER Zhang, YQ Chen, YD TI Optimal iterative increasing binary morphological filters SO OPTICAL ENGINEERING LA English DT Article DE digital document; iterative filter; morphological filter; optimal filter ID CONDITIONAL-EXPECTATION; REPRESENTATION AB Rather than design an optimal filter over a large window, which may be computationally impossible or require unacceptable computation time, one can design an iterative filter, each stage of which is designed over a small window with acceptable design time. If a two-stage iterative filter is designed with each stage optimally designed over a window, then the iterative filter is a suboptimal approximation to the optimal filter over the larger window formed as the dilation of the small window with itself. Using image-noise models, three basic questions regarding optimal increasing iterative filters are statistically addressed: How many iterations are required before there is only a negligible increase in filter performance? As the number of iterations increases, how good is filter performance in comparison with large-window noniterative filters? What are the logical and probabilistic relations between noniterative and approximating interative filters? Iterative-filter performance is seen to be only slightly suboptimal, in return for tractable design. A key conclusion is that, while in terms of logic there may be a significant difference between a noniterative and approximating iterative filter, their probabilistic difference as operators on random sets can be neglible. This fundamental point is discussed in the context of application to digital document processes, which form a key area of application. (C) 1996 society of Photo-Optical Instrumentation Engineers. C1 TEXAS A&M UNIV,DEPT ELECT ENGN,WISENBAKER ENGN RES CTR 215,COLLEGE STN,TX 77843. XEROX CORP,MS 0147 15B,WEBSTER,NY 14580. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Dougherty, ER (reprint author), TEXAS A&M UNIV,CTR APPL TECHNOL,COLLEGE STN,TX 77843, USA. NR 19 TC 14 Z9 14 U1 0 U2 0 PU SOC PHOTO-OPT INSTRUM ENG PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 SN 0091-3286 J9 OPT ENG JI Opt. Eng. PD DEC PY 1996 VL 35 IS 12 BP 3495 EP 3507 DI 10.1117/1.601086 PG 13 WC Optics SC Optics GA VX100 UT WOS:A1996VX10000021 ER PT J AU Szallasi, A Blumberg, PM AF Szallasi, A Blumberg, PM TI Vanilloid receptors: New insights enhance potential as a therapeutic target SO PAIN LA English DT Review DE capsaicin; resiniferatoxin; vanilloid receptors; messenger plasticity; neuropathic pain; neurogenic inflammation ID DORSAL-ROOT GANGLION; NERVE GROWTH-FACTOR; PRIMARY SENSORY NEURONS; NEONATAL CAPSAICIN TREATMENT; PERFUSED RAT HINDLIMB; H-3 RESINIFERATOXIN BINDING; PRIMARY AFFERENT NEURONS; GENE-RELATED PEPTIDE; SUBSTANCE-P CONTENT; TOPICAL CAPSAICIN AB Compounds related to capsaicin and its ultrapotent analog, resiniferatoxin (RTX), collectively referred to as vanilloids, interact at a specific membrane recognition site (vanilloid receptor), expressed almost exclusively by primary sensory neurons involved in nociception and neurogenic inflammation. Desensitization to vanilloids is a promising therapeutic approach to mitigate neuropathic pain and pathological conditions (e.g. vasomotor rhinitis) in which neuropeptides released from primary sensory neurons play a major role. Capsaicin-containing preparations are already commercially available for these purposes. The use of capsaicin, however, is severely limited by its irritancy, and the synthesis of novel vanilloids with an improved pungency/desensitization ratio is an on-going objective. This review highlights the emerging evidence that the vanilloid receptor is not a single receptor but a family of receptors, and that these receptors recognize not simply RTX and capsaicin structural analogs but are broader in their ligand-binding selectivity. We further focus on ligand-induced messenger plasticity, a recently discovered mechanism underlying the analgesic actions of vanilloids. Lastly, we give a brief overview of the current clinical uses of vanilloids and their future therapeutic potential. The possibility is raised that vanilloid receptor subtype-specific drugs may be synthesized, devoid of the undesirable side-effects of capsaicin. C1 KAROLINSKA INST, DEPT PHYSIOL & PHARMACOL, DIV PHARMACOL, STOCKHOLM, SWEDEN. NCI, LCCTP, MOL MECH TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. NR 177 TC 170 Z9 174 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 1996 VL 68 IS 2-3 BP 195 EP 208 DI 10.1016/S0304-3959(96)03202-2 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA WD199 UT WOS:A1996WD19900002 PM 9121806 ER PT J AU Teigen, PM AF Teigen, PM TI One hundred books famous in medicine - Norman,HF SO PAPERS OF THE BIBLIOGRAPHICAL SOCIETY OF AMERICA LA English DT Book Review RP Teigen, PM (reprint author), NATL LIB MED,HIST MED DIV,BETHESDA,MD 20894, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIBLIOGRAPHICAL SOC AMER PI NEW YORK PA BOX 397 GRAND CENTRAL STATION, NEW YORK, NY 10163 SN 0006-128X J9 PAP BIBLIOGR SOC AM JI Pap. Bibliogra. Soc. Am. PD DEC PY 1996 VL 90 IS 4 BP 510 EP 512 PG 3 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA WA886 UT WOS:A1996WA88600008 ER PT J AU Chan, MS Hall, BF Bundy, DAP AF Chan, MS Hall, BF Bundy, DAP TI Modelling of potential schistosomiasis vaccination programmes SO PARASITOLOGY TODAY LA English DT Editorial Material C1 NIAID, BETHESDA, MD 20852 USA. RP Chan, MS (reprint author), UNIV OXFORD, CTR EPIDEMIOL INFECT DIS, S PARKS RD, OXFORD OX1 3PS, ENGLAND. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD DEC PY 1996 VL 12 IS 12 BP 457 EP 460 DI 10.1016/S0169-4758(96)30031-8 PG 4 WC Parasitology SC Parasitology GA VU949 UT WOS:A1996VU94900002 ER PT J AU Lee, WA Kim, WH Kim, YI Yang, HK Kim, JP Kleinman, HK AF Lee, WA Kim, WH Kim, YI Yang, HK Kim, JP Kleinman, HK TI Overexpression of the 67 kD laminin receptor correlates with the progression of gastric carcinoma SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE 67 kD laminin receptor; invasiveness; gastric carcinoma ID RING-CELL CARCINOMAS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; MESSENGER-RNA; HUMAN COLON; TUMOR PROGRESSION; BREAST-CANCER; EXPRESSION; PROLIFERATION; METASTASIS AB This retrospective study was designed to investigate the relationship between overexpression of the 67 KD laminin receptor (67LR) using immunohistochemistry, and several clinicopathological parameters including overall survival in human gastric adenocarcinoma. We stained paraffin-embedded sections of 93 resected primary gastric adenocarcinomas using a polyclonal antibody specific for the 67LR as well as monoclonal antibodies for p53 protein, epidermal growth factor receptor, proliferating cell nuclear antigen, carcinoembryonic antigen and chromagranin. The results showed statistically significant correlations between overexpression of the 67LR and types of early or advanced gastric carcinoma (p < 0.001), depth of invasion (p < 0.001), WHO histopathologic classification (p < 0.001), stage (p = 0.001), expression of p53 protein (p = 0.019), expression of epidermal growth factor receptor (p < 0.001) and proliferating cell nuclear antigen labeling index (p = 0.002). A lower proportion of signet ring cells revealed a higher percentage of overexpression of 67LR in both early (p < 0.002) and advanced (p < 0.001) gastric carcinomas. Intestinal type adenocarcinoma (according to Lauren's classification) revealed a higher percentage of overexpression of the 67LR than the diffuse type in both early (p = 0.057) and advanced (p < 0.001) gastric carcinomas. The correlations between overexpression of the 67LR and lymph node metastasis were statistically significant (p < 0.07). Although the overexpression of the 67LR tended to correlate with lower survival rates, the correlation was not statistically significant due to the limited sample size. Our data revealed that overexpression of the 67LR is correlated with the progression of gastric carcinoma. The expression of the 67LR may be important as one of the steps which determines invasiveness during the progression of cancer. C1 SEOUL NATL UNIV,COLL MED,DEPT PATHOL,SEOUL 110799,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,DEPT SURG,SEOUL 110799,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,CTR CANC RES,SEOUL 110799,SOUTH KOREA. NIDR,NIH,DEV BIOL LAB,BETHESDA,MD 20892. RI Kim, Wooho/G-3703-2011; Seoul National University, Pathology/B-6702-2012; Yang, Han-Kwang/J-2767-2012 NR 29 TC 11 Z9 12 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PD DEC PY 1996 VL 192 IS 12 BP 1195 EP 1201 PG 7 WC Pathology SC Pathology GA WJ382 UT WOS:A1996WJ38200003 PM 9182288 ER PT J AU SanzOrtega, J SanzEsponera, J Caldes, T delaConcha, EG Sobel, ME Merino, MJ AF SanzOrtega, J SanzEsponera, J Caldes, T delaConcha, EG Sobel, ME Merino, MJ TI LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions - Prognostic implications SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE gastric cancer; chromosome 5p21; loss of heterozygosity; microdissection ID NONPOLYPOSIS COLON-CANCER; CA-REPEAT POLYMORPHISM; MICROSATELLITE INSTABILITY; APC GENE; PANCREATIC-CANCER; CARCINOMA; MUTATIONS; HETEROZYGOSITY; CHROMOSOME-5Q; OCCUR AB The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhession molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84 % of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3 % at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV MADRID,HOSP SAN CARLOS,MADRID 3,SPAIN. RI Sanz, Julian/G-5276-2013 NR 34 TC 25 Z9 30 U1 0 U2 3 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PD DEC PY 1996 VL 192 IS 12 BP 1206 EP 1210 PG 5 WC Pathology SC Pathology GA WJ382 UT WOS:A1996WJ38200005 PM 9182290 ER PT J AU Clemens, J Albert, MJ Rao, M Huda, S Qadri, F VanLoon, FPL Pradhan, B Naficy, A Banik, A AF Clemens, J Albert, MJ Rao, M Huda, S Qadri, F VanLoon, FPL Pradhan, B Naficy, A Banik, A TI Sociodemographic, hygienic and nutritional correlates of Helicobacter pylori infection of young Bangladeshi children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Helicobacter pylori; Bangladesh; infection; nutrition; hygiene ID PERUVIAN CHILDREN; LIVING-CONDITIONS; RISK; CHILDHOOD; EPIDEMIOLOGY; CHOLERA; SEROPREVALENCE; TRANSMISSION; ANTIBODIES; PREVALENCE AB Background. By the age of 10 years most children in developing countries have been infected by Helicobacter pylori Identification of clues to modes of transmission of this organism to children, as well as evaluation of the sequelae of childhood infections, constitute important research priorities for developing countries. Objectives. To evaluate demographic, socioeconomic and hygienic factors associated with acquisition of infection by H. pylori early in childhood among Bangladeshi children ages 2 to 5 years and to assess whether infection by H. pylori was associated with poor nutritional status in these children and in an older group ages 6 to 9 years. Methods. A random population-based survey of 257 rural Bangladeshi children ages 2 to 5 years and 312 children ages 6 to 9 years, Seropositivity for H. pylori, as manifested by the presence of serum IgG anti-H. pylori antibodies, was correlated with nutritional status of the sampled children and with sociodemographic features and access to clean water and latrine facilities among families of the children. Results. Among children ages 2 to 5 years, the 123 (48%) who were infected by A pylori were similar to the 134 noninfected children with respect to socioeconomic level, family access to tube well water and family ownership of a latrine, However, families of infected children had more persons per sleeping room in the home (3.8 vs. 3.2, P < 0.05) and were more likely to be Hindu (20% vs. 10%, P < 0.05), Infected children did not differ significantly from noninfected children in Z scores for weight-for-age (-2.66 vs, -2.78), weight-for-height (-1.17 vs. -1.28) or height-for-age (-3.58 vs, -3.56), Analysis of survey children ages 6 to 9 years also revealed similar nutritional indexes among infected vs, noninfected children. Conclusions. Household crowding and behaviors that differ between Hindus and Muslims, but not lack of access to clean water and latrines, may enhance the transmission of H. pylori to rural Bangladeshi children, Although confirming the high frequency of infections in young Bangladeshi children, our findings do not support the notion that H. pylori is responsible for the high prevalence of malnutrition in this setting. C1 INT CTR DIARRHOEAL DIS RES,DHAKA,BANGLADESH. CTR DIS CONTROL & PREVENT,DIV IMMUNIZAT,ATLANTA,GA. RP Clemens, J (reprint author), NICHHD,EPIDEMIOL BRANCH,6100 EXECUT BLVD,ROOM 7B03,BETHESDA,MD 20892, USA. NR 30 TC 35 Z9 36 U1 0 U2 1 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 DEC PY 1996 VL 15 IS 12 BP 1113 EP 1118 DI 10.1097/00006454-199612000-00012 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VY110 UT WOS:A1996VY11000011 PM 8970222 ER PT J AU Hill, SC Damaska, BM Tsokos, M Kreps, C Brady, RO Barton, NW AF Hill, SC Damaska, BM Tsokos, M Kreps, C Brady, RO Barton, NW TI Radiographic findings in type 3b Gaucher disease SO PEDIATRIC RADIOLOGY LA English DT Article ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; REPLACEMENT THERAPY; APPEARANCE; LIVER; CT AB The purpose of this paper is to describe the radiographic findings in type 3b Gaucher disease, a chronic neuronopathic form of the illness with severe systemic manifestations. Between 1980 and 1985 17 consecutive patients were evaluated with radiography of the chest, long bones and spine, CT of the head and chest, abdominal sonography, and MRI of the head, abdomen and spine. Clinical manifestations were severe, and led to death from hepatic, pulmonary or cardiac failure in nine patients. Type 3b Gaucher disease shares the same spectrum of radiographic findings observed in type 1 disease, but the systemic manifestations are more severe. Pulmonary infiltrates, thoracic lymph node enlargement, vertebral compression fractures and osteonecrosis of the long bones occur much more frequently in patients with type 3b disease. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,PATHOL LAB,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. RP Hill, SC (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C-660,10 CTR DR MSC 1182,BETHESDA,MD 20892, USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD DEC PY 1996 VL 26 IS 12 BP 852 EP 860 PG 9 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA VX131 UT WOS:A1996VX13100004 PM 8929296 ER PT J AU Belman, AL Muenz, LR Marcus, JC Goedert, JJ Landesman, S Rubinstein, A Goodwin, S Durako, S Willoughby, A AF Belman, AL Muenz, LR Marcus, JC Goedert, JJ Landesman, S Rubinstein, A Goodwin, S Durako, S Willoughby, A TI Neurologic status of human immunodeficiency virus 1-infected infants and their controls: A prospective study from birth to 2 years SO PEDIATRICS LA English DT Article DE pediatric acquired immunodeficiency syndrome and human immunodeficiency virus; central nervous system; human immunodeficiency virus and acquired immunodeficiency syndrome encephalopathy; human immunodeficiency virus 1-associated central nervous system disease ID IMMUNE-DEFICIENCY SYNDROME; PERINATAL HIV-INFECTION; EARLY DIAGNOSIS; CHILDREN; ENCEPHALOPATHY; SURVIVAL; MOTHERS AB Objective. To determine the timing, extent, severity, and persistence of neurologic abnormalities in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection compared with similar uninfected children of HIV-I-infected women and control children; Methods. Serial neurologic examinations and head circumference measurements were performed on a cohort of HIV-I-infected children horn to HIV-l-infected women, seroreverting children born to HIV-I-infected women, and control children born to uninfected women. Examination data from 32 HIV-1-infected children, 99 reverters, and 116 control children were summarized by eight neurologic domains. Data were analyzed by longitudinal analysis. Results. Reverter children were not different from control children in neurologic function for any of the eight domains or head circumference. HIV-1-infected children had significantly more neurologic problems than the control and reverter children for seven of the eight domains. The HIV-l-infected children were further classified by whether they had acquired immunodeficiency syndrome (AIDS)-defining clinical conditions (other than lymphoid interstitial pneumonitis) in the first 24 months of life (the AIDS-opportunistic infection group) or did not (the infected-other group). Neurologic abnormalities were early, severe, pervasive, and persistent in the AIDS-opportunistic infection group, and nearly all in this group had head circumference measurements below the 10th percentile. The infected-other group had no statistically significant differences from the uninfected children, although individual children in the infected-other group had some abnormalities. Conclusions. In utero exposure to HIV-1 without infection seems to have no negative impact on neurologic function in children in the first 2 years of life. Among children with perinatally acquired HIV-I infection, the most severe and pervasive neurologic problems occur in those children who have early serious HIV-1 clinical disease. Most children without serious AIDS-defining clinical conditions in the first 2 years of life are also free from serious neurologic problems during that period. C1 WESTAT CORP,ROCKVILLE,MD. SUNY HLTH SCI CTR,DEPT NEUROL,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT INTERNAL MED,BROOKLYN,NY 11203. NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DEPT ALLERGY & IMMUNOL,BRONX,NY 10467. NICHHD,PEDIAT ADOLESCENT & MAT AIDS BRANCH,CTR RES MOTHERS & CHILDREN,ROCKVILLE,MD. RP Belman, AL (reprint author), SUNY STONY BROOK,HLTH SCI CTR,DEPT NEUROL,HSC TOWER 12,STONY BROOK,NY 11794, USA. FU NCI NIH HHS [N01-CP-31041-03]; NICHD NIH HHS [N01-HD-8-2913] NR 22 TC 26 Z9 28 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1996 VL 98 IS 6 BP 1109 EP 1118 PG 10 WC Pediatrics SC Pediatrics GA VW531 UT WOS:A1996VW53100016 PM 8951261 ER PT J AU Buolamwini, JK Raghavan, K Fesen, MR Pommier, Y Kohn, KW Weinstein, JN AF Buolamwini, JK Raghavan, K Fesen, MR Pommier, Y Kohn, KW Weinstein, JN TI Application of the electrotopological state index to QSAR analysis of flavone derivatives as HIV-1 integrase inhibitors SO PHARMACEUTICAL RESEARCH LA English DT Article DE electrotopological state index; quantitative structure-activity relationships; HIV-1 integrase inhibitors; flavones; partial least squares ID FIELD ANALYSIS COMFA; CLEAVAGE; DNA AB Purpose. A QSAR study based on electrotopological state (E-state) indices was conducted for a series of flavone HIV-1 integrase inhibitors to guide drug design. Methods. E-state indices formulated to encode electronic and topological information for each skeletal atom in a molecule (Kier and Hall Pharm. Res. 7:801-807 (1990)) were calculated using the Molconn-X program, and partial least squares (PLS) multivariate regression was used to derive QSAR models. Rasults. Predictive models with correlation coefficients (r(2)) of 0.98 (3 PLS components) and 0.99 (5 PLS components) and corresponding cross-validated correlation coefficients (c.v. r(2)) of 0.51 and 0.73, were obtained for inhibition of cleavage and integration, respectively, with one molecule omitted from the analysis. Conclusions. E-state indices at C6, C3', C5', C5, and O4 were found to be more important for prediction of activity than those for any of the other 12 flavone skeletal atoms that are common to the molecules in the data set. C1 UNIV MISSISSIPPI,SCH PHARM,NATL CTR DEV NAT PROD,UNIVERSITY,MS 38677. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RP Buolamwini, JK (reprint author), UNIV MISSISSIPPI,DEPT MED CHEM,UNIVERSITY,MS 38677, USA. NR 17 TC 19 Z9 20 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 1996 VL 13 IS 12 BP 1892 EP 1895 DI 10.1023/A:1016005813432 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WA895 UT WOS:A1996WA89500025 PM 8987091 ER PT J AU Martinez, L Bilski, P Chignell, CF AF Martinez, L Bilski, P Chignell, CF TI Effect of magnesium and calcium complexation on the photochemical properties of norfloxacin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDUCED CUTANEOUS PHOTOTOXICITY; QUINOLONE ANTIBACTERIAL AGENTS; SERIES METAL-IONS; NALIDIXIC-ACID; OXYGEN; MICE; FLUOROQUINOLONES; BINDING; PHOTOSENSITIZATION; ABSORPTION AB The fluoroquinolone antibiotics can induce skin photosensitivity in some patients and this has been ascribed to the generation of reactive oxygen species, such as singlet oxygen (O-2[(1) Delta(g)]). We have studied the photochemical properties of the different ionized forms of the fluoroquinolone norfloxacin upon complexation with Mg2+ and Ca2+ ions, as it is proposed that the antibiotic exists mainly as a complex in the blood plasma. We found that the norfloxacin cation (pH < 6) shows no photodegradation after UVA irradiation and has a low quantum yield of O-2((1) Delta(g)) generation, The norfloxacin cation does not complex Ca2+ or Mg2+ ions; when these ions are added to the solution, we observed no changes in the fluorescence quantum yields (Phi(flu)) and singlet oxygen yields (Phi(Delta)). In contrast, the neutral (6 less than or equal to pH less than or equal to 8.5) and anionic (pH > 9) forms of norfloxacin are able to complex calcium and magnesium, and their generation of O-2((1) Delta(g)) is decreased by complexation, The neutral zwitterionic form and the anionic form also quench singlet oxygen by both chemical and physical pathways regardless of complex formation, while physical quenching is observed for the cation, At pH greater than or equal to 7.4, norfloxacin photobleaches and complexation to Ca2+ and Mg2+ increases the rate at which photobleaching occurs, Thus, both the pH of the medium and complexation with metal cations may affect the phototoxic potential of this antibiotic. RP Martinez, L (reprint author), NIEHS,MOL BIOPHYS LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 23 Z9 25 U1 0 U2 13 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD DEC PY 1996 VL 64 IS 6 BP 911 EP 917 DI 10.1111/j.1751-1097.1996.tb01855.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VY601 UT WOS:A1996VY60100004 ER PT J AU Taitelbaum, H Yen, A Kopelman, R Havlin, S Weiss, GH AF Taitelbaum, H Yen, A Kopelman, R Havlin, S Weiss, GH TI Effects of bias on the kinetics of A+B->C with initially separated reactants SO PHYSICAL REVIEW E LA English DT Article ID REACTION-DIFFUSION SYSTEM; REACTION FRONT; FLUCTUATIONS AB The effects of a constant field on the early-time kinetic behavior of the A+B-->C reaction-diffusion system with initially separated reactants are analyzed. This is in order to account for the pressure effect resulting from the injection of the reactants on both sides of the experimental capillary. The kinetics at early times depends on the magnitude of the field relative to the reaction rate constant, in a suitable set of units. An approximate solution is given for the case in which the effect of the reaction is smaller than that of the bias. We show that the production rate of C is initially proportional to t(1/2) with a crossover to proportionality to t, a behavior which has been experimentally observed. The converse case, in which the effect of the bias is smaller than that of the reaction, has been studied numerically, and exhibits effects of bias only in the lone-time limit. C1 UNIV MICHIGAN,DEPT CHEM,ANN ARBOR,MI 48109. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Taitelbaum, H (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. NR 10 TC 20 Z9 20 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD DEC PY 1996 VL 54 IS 6 BP 5942 EP 5947 DI 10.1103/PhysRevE.54.5942 PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA WA839 UT WOS:A1996WA83900014 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Role of calcium in endothelin-induced contractions and prostacyclin release SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PROTEIN-KINASE-C; VASCULAR SMOOTH-MUSCLE; MESANGIAL CELLS; RECEPTOR; INVOLVEMENT; EXPRESSION; CLONING; AORTA AB Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that induces characteristically long-lasting contractions. We used rat aortic rings to investigate the role of protein kinase C (PKC) in ET-1-induced contractions and prostacyclin (PGI(2)) release. ET-(1) (10(-9) M) produced a gradual and sustained contraction in rat aortic rings. Pretreatment of aortic rings with different doses (10(-9) M and 10(-6) M) of diltiazem (voltage-sensitive L-type calcium channel blocker) produced significant inhibition of ET-1- and PDBu-induced contractions and PGI(2) release. Inhibition was first noted at 10(-9) M and was complete at 10(-6) M. Conversely, pretreatment of aortic rings with different doses (10(-9) M and 10(-6) M) of calcium channel blockers (thapsigargin, an intracellular calcium channel blocker, or conotoxin, a voltage-sensitive N-type calcium channel blocker) produced no changes on ET-1- or PDBu-induced contraction or PGI(2) release. These results provide further support for the concept that PKC mediates ET-induced contractions and PGI(2) release in rat aortic rings via an increase in intracellular calcium and this increase is due to the influx of extracellular calcium and not to the release of calcium from the sarcoplasmic reticulum. RP Oriji, GK (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BLDG 10,ROOM 8C103,10 CTR DR,MSC 1754,BETHESDA,MD 20892, USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 1996 VL 55 IS 6 BP 413 EP 417 DI 10.1016/S0952-3278(96)90124-6 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA WA458 UT WOS:A1996WA45800006 PM 9014219 ER PT J AU Kervinen, J Thanki, N Zdanov, A Tino, J Barrish, J Lin, PF Colonno, R Riccardi, K Samanta, H Wlodawer, A AF Kervinen, J Thanki, N Zdanov, A Tino, J Barrish, J Lin, PF Colonno, R Riccardi, K Samanta, H Wlodawer, A TI Structural analysis of the native and drug-resistant HIV-1 proteinases complexed with an aminodiol inhibitor SO PROTEIN AND PEPTIDE LETTERS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITORS; REDUCED SENSITIVITY; CRYSTAL-STRUCTURE; DESIGN; MUTANT AB Crystal structures of the native HIV-1 proteinase and an A71T/V82A mutant have been solved in complexes with a symmetric aminodiol inhibitor, BMS-182193. Some of the conformational differences between these two complexes can be traced to their non-isomorphous crystal forms, but numerous rearrangements due to mutations are clearly visible. The V82A mutation creates more space at the periphery of the active site cleft, allowing distal parts of the inhibitor to move more freely, whereas the non-active-site mutation A71T stabilizes the enzyme backbone. The role of mutations in eliciting drug resistance is discussed. C1 NCI,MACROMOL STRUCT INST,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,WALLINGFORD,CT 06492. NR 21 TC 19 Z9 19 U1 0 U2 0 PU BENTHAM SCIENCE PUBL BV PI SCHIPHOL PA PO BOX 75676, 1118 ZS SCHIPHOL, NETHERLANDS SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD DEC PY 1996 VL 3 IS 6 BP 399 EP 406 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW062 UT WOS:A1996VW06200007 ER PT J AU ElKabbani, O Carper, DA McGowan, MH Ginell, SL AF ElKabbani, O Carper, DA McGowan, MH Ginell, SL TI Crystal structure of porcine aldehyde reductase at 2.0 angstrom resolution: Modeling an inhibitor in the active site of the enzyme SO PROTEIN AND PEPTIDE LETTERS LA English DT Article ID ALDOSE REDUCTASE; DIABETIC COMPLICATIONS; MECHANISM; BINDING AB Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The X-ray crystal structure of porcine aldehyde reductase holoenzyme has been refined to a crystallographic R-factor of 0.20 at 2.0 Angstrom resolution. We have modeled the inhibitor zopolrestat in the active site of porcine aldehyde reductase in order to obtain a picture of the binding conformation of inhibitors to the enzyme. C1 UNIV ALABAMA,CTR MACROMOL CRYSTALLOG,BIRMINGHAM,AL 35294. NEI,NIH,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,NATL SYNCHROTRON LIGHT SOURCE DEPT,ARGONNE NATL LAB,STRUCT BIOL CTR,UPTON,NY 11973. NR 20 TC 8 Z9 8 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI SCHIPHOL PA PO BOX 75676, 1118 ZS SCHIPHOL, NETHERLANDS SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD DEC PY 1996 VL 3 IS 6 BP 427 EP 434 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW062 UT WOS:A1996VW06200011 ER PT J AU Alesker, V Nussinov, R Wolfson, HJ AF Alesker, V Nussinov, R Wolfson, HJ TI Detection of non-topological motifs in protein structures SO PROTEIN ENGINEERING LA English DT Article DE analysis of crystallographic databases; computer vision; geometric hashing; protein structure comparison; topological motifs ID VISION-BASED TECHNIQUE; AMINO-ACID SEQUENCE; SPATIAL ARRANGEMENTS; SECONDARY STRUCTURE; STRUCTURE ALIGNMENT; ESCHERICHIA-COLI; DATA-BANK; EVOLUTION; IDENTIFICATION; SIMILARITIES AB We present an efficient technique for the comparison of protein structures, The algorithm uses a vector representation of the secondary structure elements and searches for spatial configurations of secondary structure elements in proteins, In such recurring protein folds, the order of the secondary structure elements in the protein chains is disregarded, The method is based on the geometric hashing paradigm and implements approaches originating in computer vision. It represents and matches the secondary structure element vectors in a 3-D translation and rotation invariant manner, The matching of a pair of proteins takes on average under 3 s on a Silicon Graphics Indigo2 workstation, allowing extensive all-against-all comparisons of the data set of non-redundant protein structures, Here we have carried out such a comparison for a data set of over 500 protein molecules, The detection of recurring topological and non-topological, secondary structure element order-independent protein folds may provide further insight into evolution, Moreover, as these recurring folding units are likely to be conformationally favourable, the availability of a data set of such topological moths can serve as a rich input for threading routines. Below, we describe this rapid technique and the results it has obtained, While some of the obtained matches conserve the order of the secondary structure elements, others are entirely order independent, As an example, we focus on the results obtained for Che Y, a signal transduction protein, and on the profilin-beta-actin complex, The Che Y molecule is composed of a five-stranded, parallel beta-sheet flanked by five helices. Here we show its similarity with the Escherichia call elongation factor, with L-arabinose binding protein, with haloalkane dehalogenase and with adenylate kinase, The profilin-beta-actin contains an antiparallel beta-pleated sheet with alpha-helical termini, Its similarities to lipase, fructose disphosphatase and beta-lactamase are displayed. C1 TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,FAC MED,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. NCI,MATH BIOL LAB,SAIC,FCRDC,FREDERICK,MD 21702. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 39 TC 27 Z9 27 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 DEC PY 1996 VL 9 IS 12 BP 1103 EP 1119 DI 10.1093/protein/9.12.1103 PG 17 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WB714 UT WOS:A1996WB71400004 PM 9010924 ER PT J AU Yang, YS Marshall, AD McPhie, P Guo, WXA Xie, XF Chen, X Jakoby, WB AF Yang, YS Marshall, AD McPhie, P Guo, WXA Xie, XF Chen, X Jakoby, WB TI Two phenol sulfotransferase species from one cDNA: Nature of the differences SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID ARYL SULFOTRANSFERASE; CIRCULAR-DICHROISM; RAT-LIVER; PROTEINS; IV AB A phenol sulfotransferase from rat liver (EC 2.8.2.9), expressed in Escherichia coli from a single cDNA, was purified as two separable but catalytically active proteins. The proteins appeared to be identical to each other and to the natural liver sulfotransferase by comparison of their amino acid constitution, amino-terminal end group, and interaction with a polyclonal antibody raised against the liver enzyme. Each of the recombinant forms, alpha and beta, catalyzed the sulfuryl group transfer from 4-nitrophenylsulfate to an acceptor phenol, a reaction in which 3'-phospho-adenosine 5'-phosphate (PAP) is a necessary intermediate. Only form beta, however, catalyzes the physiological transfer of a sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the free phenol. Evidence is presented that sulfotransferase alpha, but not beta, has 1 mol of PAP tightly bound per enzyme dimer. The ability to utilize PAPS as a sulfate donor could be altered: form alpha could be treated and purified as form beta to acquire the ability to use PAPS, whereas form beta was treated by extended incubation with PAP, lost its ability to use PAPS, and was purified as form alpha. (C) 1996 Academic Press, Inc. C1 NIDDK,NATL INST HLTH,SECT ENZYMES,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 13 TC 26 Z9 27 U1 1 U2 1 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 DEC PY 1996 VL 8 IS 4 BP 423 EP 429 DI 10.1006/prep.1996.0120 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VX143 UT WOS:A1996VX14300005 PM 8954889 ER PT J AU Pikaart, MJ Felsenfeld, G AF Pikaart, MJ Felsenfeld, G TI Expression and codon usage optimization of the erythroid-specific transcription factor cGATA-1 in baculoviral and bacterial systems SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; FACTOR GATA-1; DNA; PROTEIN; GENES; COMPLEX; CELLS AB Biochemical characterization of cGATA-1,(1) a key transcription factor in the regulation of globin expression in chickens, has been precluded by the unavailability of appreciable amounts of the pure protein. Purification directly from embryonic red blood cells has been limited by the difficulty in obtaining large quantities of the starting material, and previous attempts at bacterial expression have consistently yielded truncated product. To solve these problems, we have taken two approaches to the expression of cGATA-1. First, we were able to produce efficient expression from baculovirus-infected insect cells. Second, by altering the codon usage in cDNA encoding the protein's carboxy-terminal region, we obtained good expression of full-length protein in Escherichia coli. These preparations should prove useful in biochemical and structural studies of the factor. Additionally, we describe a primer extension/PCR-based method which can be used to synthesize extended regions of DNA sequence for gene construction. (C) 1996 Academic Press, Inc. RP Pikaart, MJ (reprint author), NIDDK,NATL INST HLTH,MOL BIOL LAB,BETHESDA,MD 20892, USA. NR 22 TC 11 Z9 11 U1 1 U2 1 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 DEC PY 1996 VL 8 IS 4 BP 469 EP 475 DI 10.1006/prep.1996.0126 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VX143 UT WOS:A1996VX14300011 PM 8954895 ER PT J AU Stratikos, E Alberdi, E Gettins, PGW Becerra, SP AF Stratikos, E Alberdi, E Gettins, PGW Becerra, SP TI Recombinant human pigment epithelium-derived factor (PEDF): Characterization of PEDF overexpressed and secreted by eukaryotic cells SO PROTEIN SCIENCE LA English DT Article DE circular dichroism; fluorescence enhancement; heparin binding; mammalian overexpression; pigment epithelium-derived factor; serpin ID HUMAN ANTITHROMBIN-III; MAJOR BASIC-PROTEIN; NEUROTROPHIC ACTIVITY; CRYSTAL-STRUCTURE; HEPARIN-BINDING; IDENTIFICATION; PLASMA; INHIBITOR; OVALBUMIN; ANGIOTENSINOGEN AB Pigment epithelium-derived factor (PEDF) is a serpin found in the interphotoreceptor matrix of the eye, which, although not a proteinase inhibitor, possesses a number of important biological properties, including promotion of neurite outgrowth and differential expression in quiescent versus senescent states of certain cell types. The low amounts present in the eye, together with the impracticality of using the eye as a source for isolation of the human protein, make it important to establish a system for overexpression of the recombinant protein for biochemical and biological studies. We describe here the expression and secretion of full-length glycosylated human recombinant PEDF at high levels (>20 mu g/mL) into the growth medium of baby hamster kidney cells and characterization of the purified rPEDF by circular dichroism and fluorescence spectroscopies and neurite outgrowth assay. By these assays, the recombinant protein behaves as expected for a correctly folded full-length human PEDE The availability of milligram amounts of PEDF has permitted quantitation of its heparin binding properties and of the effect of reactive center cleavage on the stability of PEDF towards thermal and guanidine hydrochloride denaturation. C1 UNIV ILLINOIS,DEPT BIOCHEM,CHICAGO,IL 60612. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. OI Stratikos, Efstratios/0000-0002-3566-2309 FU NHLBI NIH HHS [HL49234] NR 32 TC 46 Z9 46 U1 2 U2 5 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 DEC PY 1996 VL 5 IS 12 BP 2575 EP 2582 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA115 UT WOS:A1996WA11500020 PM 8976566 ER PT J AU Zhong, M Wu, C AF Zhong, M Wu, C TI Proteolytic mapping of heat shock transcription factor domains SO PROTEIN SCIENCE LA English DT Article DE heat shock factor; protease mapping; protein conformation ID DNA-BINDING DOMAIN; INDUCED CONFORMATIONAL CHANGE; COILED-COIL; MOLECULAR-CLONING; ACTIVATION; YEAST; TRANSITION; PROTEINS; STRESS; HSF1 AB Heat shock transcription factors (HSFs) of higher eukaryotes respond to physical and cellular stress signals by trimerizing, binding to a specific site on DNA, and transactivating genes encoding the heat shock proteins. In this work, limited proteolysis was used as a biochemical probe of the domain organization of Drosophila HSF. Both unshocked monomeric and heat-shocked trimeric HSF possess an internal protease-sensitive region located between the aminoterminal and carboxy-terminal hydrophobic heptad repeats, suggesting that this is a less structured region compared to those defined for DNA-binding, trimerization, and transactivation. For a few cleavage sites, the heat-shocked form of HSF is more accessible to proteases than the unshocked form, providing an additional diagnostic marker for inducible changes in conformation or modification between the latent and activated farms of HSF. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI yu, yan/C-2322-2012 NR 42 TC 7 Z9 7 U1 1 U2 3 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 DEC PY 1996 VL 5 IS 12 BP 2592 EP 2599 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA115 UT WOS:A1996WA11500022 PM 8976568 ER PT J AU Lebowitz, BD Light, E AF Lebowitz, BD Light, E TI The aging caregivers of psychiatric patients: Healthcare perspectives SO PSYCHIATRIC ANNALS LA English DT Article ID FAMILY CAREGIVERS; DEPRESSIVE-DISORDERS; SPOUSE-CAREGIVERS; ADULT CHILDREN; PARENTS; PREVALENCE; STRESS RP Lebowitz, BD (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,5600 FISHERS LANE,RM 18-101,ROCKVILLE,MD 20857, USA. NR 39 TC 4 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD DEC PY 1996 VL 26 IS 12 BP 785 EP 791 PG 7 WC Psychiatry SC Psychiatry GA VY487 UT WOS:A1996VY48700007 ER PT J AU Wyatt, RJ Apud, JA Potkin, S AF Wyatt, RJ Apud, JA Potkin, S TI New directions in the prevention and treatment of schizophrenia: A biological perspective SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article; Proceedings Paper CT 11th International Symposium for the Psychotherapy of Schizophrenia - Psychotherapy and Comprehensive Treatment CY JUN 12-16, 1994 CL WASHINGTON, DC ID NEUROLEPTIC MALIGNANT SYNDROME; PRENATAL EXPOSURE; INFLUENZA EPIDEMICS; ADULT SCHIZOPHRENIA; MATERNAL INFLUENZA; C-FOS; 1ST-EPISODE SCHIZOPHRENIA; CHROMOSOME 22Q12-Q13.1; CORTICAL DEVELOPMENT; SUSCEPTIBILITY GENE AB OUR current treatments for schizophrenia are, at best, palliative. With the exception of counseling those families with a known high risk for having schizophrenic offspring, no preventive measures are currently available. The not too distant future, however, promises to bring improvements in somatic treatments as well as the possible introduction of preventive measures. We are fully aware that current biological treatments work best when they are combined with psychosocial intervention, and expect that future biological treatments and preventions will also involve appropriate nonbiological considerations. Psychosocial treatments are covered elsewhere in this issue. Here we look at how modern genetics, pre- and perinatal factors, early and sustained intervention, and new medications are likely to decrease both the number of individuals with schizophrenia and the severity of the illness. C1 UNIV CALIF IRVINE,MED CTR,CALIF COLL MED,DEPT PSYCHIAT & BEHAV,IRVINE,CA 92717. RP Wyatt, RJ (reprint author), ST ELIZABETH HOSP,NIMH,WAW,NPB,NEUROSCI CTR,NEUROPSYCHIAT BRANCH,ROOM 536,WASHINGTON,DC 20032, USA. NR 85 TC 16 Z9 16 U1 2 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 1996 VL 59 IS 4 BP 357 EP 370 PG 14 WC Psychiatry SC Psychiatry GA WF723 UT WOS:A1996WF72300015 PM 9029657 ER PT J AU Malkova, L Murray, EA AF Malkova, L Murray, EA TI Effects of partial versus complete lesions of the amygdala on cross-modal associations in cynomolgus monkeys SO PSYCHOBIOLOGY LA English DT Article ID VISUAL CORTICAL AREAS; RHESUS-MONKEY; MACACA-FASCICULARIS; MEDIODORSAL NUCLEUS; CORTEX; PROJECTIONS; RECOGNITION; MEMORY; CONNECTIONS; THALAMUS AB Aspiration lesions of the amygdala plus subjacent cortex were found earlier to produce a severe impairment in cross-modal (tactual-to-visual) recognition (Murray & Mishkin, 1985). To determine whether more selective lesions would also produce this effect, we trained 8 naive cynomolgus monkeys on a tactual-visual version of delayed nonmatching-to-sample and then injected ibotenic acid bilaterally into either the basolateral (n = 4) or centromedial (n = 4) subdivisions of the amygdala. Neither of the excitotoxic lesions affected performance. In a second experiment, we aspirated the amygdala plus subjacent cortex in similarly trained monkeys. The performance of these animals fell significantly and remained substantially below preoperative levels despite extensive postoperative retraining. The findings suggest that the severe deficit in cross-modal recognition following the aspiration lesion is attributable to complete amygdala damage, damage to the subjacent cortex, or the two in combination. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. OI Murray, Elisabeth/0000-0003-1450-1642 NR 36 TC 8 Z9 8 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0889-6313 J9 PSYCHOBIOLOGY JI Psychobiology PD DEC PY 1996 VL 24 IS 4 BP 255 EP 264 PG 10 WC Psychology; Psychology, Multidisciplinary SC Psychology GA VZ282 UT WOS:A1996VZ28200001 ER PT J AU Ingraham, LJ Chan, TF AF Ingraham, LJ Chan, TF TI Is there psychopathology in the coparents of schizophrenic adoptees' half-siblings? SO PSYCHOLOGICAL REPORTS LA English DT Article ID RELATIVES AB An excess of schizophrenia has been observed in the biological relatives of adoptees with schizophrenia. The present analysis examined the possibility that illness observed among 90 half-siblings may have been influenced by assortative mating resulting in excess illness in the biological parents of the half-siblings not biologically related to the adoptees (the coparents). We found no difference in the prevalence of mental illness between 44 index and 26 control coparents. RP Ingraham, LJ (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD DEC PY 1996 VL 79 IS 3 BP 1296 EP 1298 PN 2 PG 3 WC Psychology, Multidisciplinary SC Psychology GA WD220 UT WOS:A1996WD22000042 PM 9009782 ER PT J AU Soria, R Stapleton, JM Gilson, SF SampsonCone, A Henningfield, JE London, ED AF Soria, R Stapleton, JM Gilson, SF SampsonCone, A Henningfield, JE London, ED TI Subjective and cardiovascular effects of intravenous nicotine in smokers and non-smokers SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; subjective responses; cardiovascular responses; non-smokers smokers ID CIGARETTE-SMOKING; ACUTE TOLERANCE; HEART-RATE; PERFORMANCE; ADDICTION; COCAINE AB The present study assessed the subjective and cardiovascular effects of intravenous nicotine in smokers and nonsmokers. Nonsmokers (n = 5) and smokers (n = 5) were administered a single dose of nicotine (0.75 or 1.5 mg) or saline on each of 3 days. The nicotine doses were given in ascending order in a double-blind fashion. Although smokers and nonsmokers manifested significant increases in systolic and diastolic blood pressure and heart rate 1 min after administration of all active test doses, the difference between peak heart rate and that measured at later times was greater in nonsmokers than in smokers. Nonsmokers and smokers also differed in subjective self-reports. In response to items on visual analogue scales indicative of positive effects (e.g., ''good effects,'' ''like drug,'' ''use again,'' and ''feel energetic''), smokers but not nonsmokers reported high scores (> 40) after nicotine injection. In addition, responses on the MBG and LSD subscales of the Addiction Research Center Inventory indicated that smokers experienced positive subjective effects after the test doses, whereas nonsmokers experienced disorientation. The fact that intravenous nicotine was not associated with positive subjective effects in nonsmokers indicates that repeated exposure is required to establish positive reinforcing effects of nicotine. C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. VET ADM MED CTR,NEUROL SERV,BROOKLYN,NY 11209. VIRGINIA COMMONWEALTH UNIV,SCH SOCIAL WORK,RICHMOND,VA 23284. NR 28 TC 44 Z9 44 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1996 VL 128 IS 3 BP 221 EP 226 DI 10.1007/s002130050129 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VZ287 UT WOS:A1996VZ28700001 PM 8972541 ER PT J AU Glowa, JR Wojnicki, FHE AF Glowa, JR Wojnicki, FHE TI Effects of drugs on food- and cocaine-maintained responding .3. Dopaminergic antagonists SO PSYCHOPHARMACOLOGY LA English DT Article DE self-administration; SCH23390; chlorpromazine; pimozide; CFT; reinforcement; cocaine; DA antagonists; rhesus monkeys ID SELF-ADMINISTRATION BEHAVIOR; RHESUS-MONKEYS; SQUIRREL-MONKEYS; DIFFERENT SCHEDULES; D1; RAT; REINFORCEMENT; CHLORPROMAZINE; INVOLVEMENT; RECEPTORS AB The effects of three dopamine (DA) antagonists (SCH23390, pimozide, and chlorpromazine), with various degrees of selectivity for D-1 and D-2 receptors, and an agonist (the cocaine analog, CFT) were studied on responding maintained under a multiple fixed-ratio (FR) 30 food, FR30 cocaine (1-100 mu g/kg per injection) delivery, with an interposed 10-min time-out (TO), schedule in rhesus monkeys. The effects of each drug depended upon the unit dose of cocaine. With an intermediate (10 mu g/kg per injection) unit dose of cocaine, each antagonist decreased rates of responding maintained by either event in a dose-related manner. At higher (56-100 mu g/kg per injection) unit doses of cocaine, antagonists generally increased and then decreased both food- and cocaine-maintained responding in a dose-related manner. These increases appeared to result from the blockade of non-specific rate-decreasing effects of self-administered cocaine, questioning their relevance to the reinforcing effects of cocaine. The results failed to support a role for pharmacological selectivity in this rate-decreasing effect of cocaine, as both D-1 and D-2 antagonists were able to reverse the effect. In contrast, CFT decreased cocaine-maintained responding at doses less than those that decreased food-maintained responding, and failed to shift the cocaine dose-effect function to the left. These results, together with previous work, suggest that agonists can selectively decrease drug-seeking behavior. C1 NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. RP Glowa, JR (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PHARMACOL & THERAPEUT,1501 KINGS HWY,SHREVEPORT,LA 71130, USA. FU NIDA NIH HHS [DA 09820]; ONDIEH CDC HHS [RA-ND-94-24] NR 32 TC 28 Z9 29 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1996 VL 128 IS 4 BP 351 EP 358 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WA391 UT WOS:A1996WA39100003 PM 8986005 ER PT J AU Hall, P Furst, CJ Mattsson, A Holm, LE Boice, JD Inskip, PD AF Hall, P Furst, CJ Mattsson, A Holm, LE Boice, JD Inskip, PD TI Thyroid nodularity after diagnostic administration of iodine-131 SO RADIATION RESEARCH LA English DT Article ID CANCER INCIDENCE; RADIATION; CHERNOBYL; I-131; CHILDHOOD; NODULES; FALLOUT; HYPERTHYROIDISM; NEOPLASIA; GLANDS AB In contrast to external X and gamma radiation, radiation from internally deposited I-131 has not been clearly shown to cause thyroid tumors or nodules. Given the wide use of I-131 in medicine and concern about health risks associated with the release of radioiodines from nuclear reactors, more information is needed. The purpose of this study was to evaluate the risk of thyroid nodularity among women previously exposed to radioiodine (I-131) for diagnostic reasons. A clinical examination survey, including thyroid palpation, was conducted for a sample of women drawn from a cohort of patients exposed to I-131 and a comparison group of women attending a mammography screening clinic. The study was conducted during 1991-1993 at Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. A total of 1,005 women referred for a thyroid scintigraph or tracer test during the period 1952-1977 were included in the study. For comparison, 248 nonexposed women attending a mammography screening clinic were also enrolled. The primary outcome measure was the presence or absence of palpable thyroid nodules at the time of the clinical examination. Odds ratios were used as estimates of relative risk (RR). The mean dose to the thyroid from I-131 was 0.54 Gy, and the average age at I-131 administration was 26 years. The prevalence of thyroid nodularity was 10.6% among women who had been exposed to I-131 and 11.7% among the nonexposed women [RR = 0.9; 95% confidence interval (CI) 0.6-1.4]. When analysis was restricted to women exposed to I-131, prevalence was associated positively with thyroid dose (excess RR = 0.9 per Gy; 95% CI 0.2-1.9). However, the excess RR was similar for women exposed before age 20 years and those exposed after age 20, which is contrary to findings for populations exposed to external radiation. While results demonstrated a positive association between diagnostic administration of I-131 and the subsequent occurrence of thyroid nodules, it is unclear whether the association is causal, as the possibility of confounding by indication for I-131 administration cannot be ruled out. No tumors that were subsequently diagnosed as cancer were found during the thyroid examinations, which supports the view that exposure to I-131 administered for diagnostic reasons during adulthood rarely causes thyroid cancer. (C) 1996 by Radiation Research Society C1 KAROLINSKA HOSP,CTR ONCOL,S-17176 STOCKHOLM,SWEDEN. SWEDISH RADIAT PROTECT INST,STOCKHOLM,SWEDEN. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. TEXAS A&M UNIV,COLL VET MED,COLLEGE STN,TX 77843. RP Hall, P (reprint author), KAROLINSKA HOSP,DEPT ONCOL,RADIUMHEMMET,S-17176 STOCKHOLM,SWEDEN. FU NCI NIH HHS [N01-CP-15652] NR 37 TC 11 Z9 14 U1 0 U2 0 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 DEC PY 1996 VL 146 IS 6 BP 673 EP 682 DI 10.2307/3579384 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA VW544 UT WOS:A1996VW54400011 PM 8955718 ER PT J AU Dwyer, AJ AF Dwyer, AJ TI In pursuit of a piece of the ROC SO RADIOLOGY LA English DT Editorial Material DE diagnostic radiology, observer performance; editorials; receiver operating characteristic curve (ROC); statistical analysis ID CURVES; AREA RP Dwyer, AJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C660,10 CTR DR MSC 1182,BETHESDA,MD 20892, USA. NR 11 TC 11 Z9 13 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 621 EP 625 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000008 PM 8939207 ER PT J AU Pierpaoli, C Jezzard, P Basser, PJ Barnett, A DiChiro, G AF Pierpaoli, C Jezzard, P Basser, PJ Barnett, A DiChiro, G TI Diffusion tensor MR imaging of the human brain SO RADIOLOGY LA English DT Article DE brain, MR; magnetic resonance (MR), diffusion study; magnetic resonance (MR), experimental; magnetic resonance (MR), tissue characterization ID MAGNETIC-RESONANCE; WEIGHTED MR; WATER DIFFUSION; ANALYTICAL EXPRESSIONS; NERVOUS-SYSTEM; WHITE-MATTER; IN-VIVO; ANISOTROPY; COEFFICIENTS; SPECTROSCOPY AB PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximate to 2,100 x 10(-6) mm(2)/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders. C1 NIMH,UNIT MRI PHYS,NIH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. RP Pierpaoli, C (reprint author), NINCDS,NEUROIMAGING BRANCH,NIH,BLDG 10,ROOM 1C227,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011; OI Jezzard, Peter/0000-0001-7912-2251 NR 47 TC 1562 Z9 1613 U1 5 U2 85 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 637 EP 648 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000010 PM 8939209 ER PT J AU Choyke, PL Walther, MM AF Choyke, PL Walther, MM TI Suggestions with regard to radiologic ''numeracy'' - Reply SO RADIOLOGY LA English DT Letter ID RENAL-CELL CARCINOMA RP Choyke, PL (reprint author), NIH,DEPT DIAGNOST RADIOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1996 VL 201 IS 3 BP 877 EP 878 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU500 UT WOS:A1996VU50000049 ER PT J AU Vu, V Barrett, JC Roycroft, J Schuman, L Dankovic, D Baron, P Martonen, T Pepelko, W Lai, D AF Vu, V Barrett, JC Roycroft, J Schuman, L Dankovic, D Baron, P Martonen, T Pepelko, W Lai, D TI Chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material ID WORKSHOP AB On May 8-10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina, The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended, For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels, Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-term in vitro and in vivo studies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified. (C) 1996 Academic Press, Inc. C1 US EPA,OFF POLLUT PREVENT & TOX 7403,WASHINGTON,DC 20460. NIEHS,RES TRIANGLE PK,NC 27709. NIOSH,CINCINNATI,OH. US EPA,OFF RES & DEV,RES TRIANGLE PK,NC 27711. US EPA,OFF RES & DEV,WASHINGTON,DC 20460. NR 5 TC 19 Z9 19 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 1996 VL 24 IS 3 BP 202 EP 212 DI 10.1006/rtph.1996.0128 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA WA825 UT WOS:A1996WA82500003 PM 8975745 ER PT J AU Rice, WG Turpin, JA AF Rice, WG Turpin, JA TI Virus-encoded zinc fingers as targets for antiviral chemotherapy SO REVIEWS IN MEDICAL VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 NUCLEOCAPSID PROTEIN; ACID-BINDING-PROTEINS; REVERSE TRANSCRIPTION; STRAND TRANSFER; GAG PROTEINS; HIV-1; RNA; RETROVIRUSES; INFECTIVITY RP Rice, WG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB ANTIVIRAL DRUG MECHANISMS,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 57 TC 26 Z9 27 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD DEC PY 1996 VL 6 IS 4 BP 187 EP 199 DI 10.1002/(SICI)1099-1654(199612)6:4<187::AID-RMV176>3.0.CO;2-F PG 13 WC Virology SC Virology GA VY104 UT WOS:A1996VY10400002 ER PT J AU Haseman, JK Elwell, MR AF Haseman, JK Elwell, MR TI Evaluation of false positive and false negative outcomes in NTP long-term rodent carcinogenicity studies SO RISK ANALYSIS LA English DT Article DE false positive rates; false negative rates; tumor incidence; laboratory animal carcinogenicity studies; National Toxicology Program ID LABORATORY-ANIMAL CARCINOGENICITY; TUMOR-INCIDENCE; BODY-WEIGHT; MICE; DESIGN; RATES AB The decision-making process used by the National Toxicology Program (NTP) in its evaluation of long-term rodent carcinogenicity studies was investigated to determine whether or not this procedure resulted in an excessive number of false positive or false negative outcomes, All site-specific tumor incidences that were found to be significantly (p < 0.05) increased either by a trend test or by pairwise comparisons of each dosed group against the controls in 218 NTP 2-year studies with Fischer 344 rats and/or B6C3F1 mice were tabulated and compared to the number of statistically significant tumor increases expected to occur by chance. Our evaluation suggests that false positive rates are fairly low in NTP long-term studies. Assessing false negative rates is more difficult because of the limited sensitivity of the bioassay for detecting subtle carcinogenic effects. Moreover, reduced body weights frequently occur in dosed animals, and the positive correlation between the incidences of certain site-specific tumors and body weight may mask the detection of carcinogenic effects. Despite these difficulties, our analysis did identify one tumor showing evidence of false negative outcomes: interstitial cell tumors of the testis in male Fischer 344 (F344) rats. This tumor showed considerably more significant (p < 0.05) increased incidences than expected by chance, yet none were considered to be chemically-related. However, the biological significance of interstitial cell tumor increases in F344 rats is uncertain because of the high background rate of neoplasia (>90%) for this target site. C1 NIEHS,PATHOL BRANCH,RES TRIANGLE PK,NC 27709. RP Haseman, JK (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,MD A3-03,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 23 Z9 23 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 1996 VL 16 IS 6 BP 813 EP 820 DI 10.1111/j.1539-6924.1996.tb00832.x PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA VY703 UT WOS:A1996VY70300010 PM 8972110 ER PT J AU Stewart, PA Lees, PSJ Francis, M AF Stewart, PA Lees, PSJ Francis, M TI Quantification of historical exposures in occupational cohort studies SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Review DE cohort studies; epidemiologic studies; exposure assessment ID INDUSTRY; WORKERS; FORMALDEHYDE; MORTALITY; EPIDEMIOLOGY; CANCER; MODEL; BIAS AB Relatively few investigators have estimated quantitative exposure levels in epidemiologic studies, and, for those that have, few have discussed the strengths and weaknesses of their estimation method with respect to other methods. This paper reviews the steps for developing quantitative exposure estimates that have been used in published studies. First, the qualitative considerations to be evaluated in the selection of the agent to be estimated (ie, the disease mechanism, the effects of exposure mixtures and interactions, the physical state of the agent, and the routes of exposures) are discussed. Considerations for developing exposure groups are then presented, including work history and exposure information characteristics, the homogeneity of exposures within exposure groups, the exposure estimation method, and the disease risk analyses to be performed. The various exposure estimation approaches are reviewed for their strengths and weaknesses, including the calculation of the mean exposures from existing exposure measurements, statistical models, measurement data from surrogate exposures, and professional judgment. Recommendations for future studies are provided. C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, BALTIMORE, MD USA. RP Stewart, PA (reprint author), NCI, OCCUPAT EPIDEMIOL BRANCH, EPN 418, ROCKVILLE, MD 20892 USA. NR 42 TC 52 Z9 52 U1 0 U2 5 PU SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD DEC PY 1996 VL 22 IS 6 BP 405 EP 414 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VY905 UT WOS:A1996VY90500002 PM 9000307 ER PT J AU Schiller, JT Lowy, DR AF Schiller, JT Lowy, DR TI Papillomavirus-like particles and HPV vaccine development SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE antibodies; cervical cancer; papillomavirus; vaccine; virus-like particles ID VIRUS-LIKE PARTICLES; CAPSID PROTEIN; L1 PROTEIN; NEUTRALIZING ANTIBODIES; SEROLOGICAL RESPONSE; INSECT CELLS; INFECTION; TYPE-16; IMMUNIZATION; EXPRESSION AB Human papillomavirus-like particles (VLPs), self-assembled after high level expression of the papillomavirus L1 virion capsid protein in non-mammalian cells, are attractive candidates for a subunit vaccine to prevent genital E-IPV infection and the subsequent development of cervical cancer In animal studies, purified VLPs induce high titers of antibodies against conformational type specific L1 epitopes. These antibodies neutralize homologous virions in in-vitro assays and protect against experimental challenge in several animal models. The encouraging results in animals justify the initiation of human trials of HPV VLP-based vaccines. Factors to be considered when designing these trials are discussed. (C) 1997 Academic Press Ltd. RP Schiller, JT (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 65 TC 59 Z9 62 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 1996 VL 7 IS 6 BP 373 EP 382 DI 10.1006/scbi.1996.0046 PG 10 WC Oncology SC Oncology GA XR609 UT WOS:A1996XR60900008 PM 9284529 ER PT J AU Zatz, M AF Zatz, M TI Melatonin rhythms: Trekking toward the heart of darkness in the chick pineal SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE calcium channels; circadian rhythm; entrainment; melatonin; pineal gland; serotonin N-acetyltransferase ID SEROTONIN N-ACETYLTRANSFERASE; CIRCADIAN PACEMAKER; PHOTOENDOCRINE TRANSDUCTION; DISSOCIATED CELLS; CALCIUM INFLUX; GLAND; LIGHT; PHOTORECEPTORS; OSCILLATIONS; THAPSIGARGIN AB Chick pineal cells make melatonin rhythmically, even in culture. Light pulses have two effects on these cells: acute suppression of melatonin synthesis and phase shifts (entrainment) of the underlying pacemaker. The two effects use different mechanistic pathways: the first goes through cAMP, and the second goes through the clock. Both converge on serotonin N-acetyltransferase, whose gene has recently been cloned, with cAMP acting on mRNA levels, but primarily on enzyme activity, and the clock acting primarily on mRNA levels. Aspects of calcium regulation, not yet well-understood, may impinge on both pathways. These cells also have a novel calcium channel and a novel photopigment. (C) 1996 Academic Press Ltd. RP Zatz, M (reprint author), NIMH,LAB CELLULAR & MOL REGULAT,BALTIMORE,MD 20892, USA. NR 66 TC 32 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD DEC PY 1996 VL 7 IS 6 BP 811 EP 820 DI 10.1006/scdb.1996.0099 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA WQ544 UT WOS:A1996WQ54400008 ER PT J AU Sonies, BC AF Sonies, BC TI Dysphagia and post-polio syndrome: Past, present, and future SO SEMINARS IN NEUROLOGY LA English DT Article ID POSTPOLIO SYNDROME; NEUROMUSCULAR SYMPTOMS; POLIOMYELITIS RP Sonies, BC (reprint author), NIH,DEPT REHABIL MED,SPEECH LANGUAGE PATHOL SECT,BETHESDA,MD 20892, USA. NR 52 TC 8 Z9 8 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 1996 VL 16 IS 4 BP 365 EP 370 DI 10.1055/s-2008-1040995 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA WU475 UT WOS:A1996WU47500009 PM 9112316 ER PT J AU Steele, AD Sears, JF AF Steele, AD Sears, JF TI Characterisation of rotaviruses recovered from neonates with symptomatic infection SO SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID REASSORTMENT OCCURS INVIVO; MONOCLONAL-ANTIBODIES; MOLECULAR EPIDEMIOLOGY; HYPERDIVERGENT REGION; SOUTH-AFRICA; 4TH GENE; INFANTS; NEUTRALIZATION; IDENTIFICATION; NEWBORN AB An unusually high number of diarrhoeal stools were obtained from neonates at different maternity units in Pretoria during late 1986 and the winter of 1987 and tested for the presence-of rotavirus infection. Latex agglutination assay revealed rotavirus in 67% (93/139) of the stools from newborn babies. Gel electrophoresis of the rotavirus genome showed that a genomically stable strain of rotavirus was associated with the diarrhoeal illness in all maternity units investigated. Determination of the VP6 subgroup specificity using monoclonal antibodies demonstrated that all strains were of subgroup If. Examination of the VP4 and VP7 rotavirus genes, which encode for the outer capsid neutralisation proteins of the virus, was conducted by hybridisation analysis using probes directed at the divergent regions of the two genes. These results showed the presence of a VP7 serotype G4 rotavirus strain with a P6 VP4 genotype - the putative 'attenuated' VP4 gene allele circulating in all maternity units studied. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP Steele, AD (reprint author), MED UNIV S AFRICA,MRC,DIARRHOEAL PATHOGENS RES UNIT,ZA-0204 MEDUNSA,SOUTH AFRICA. NR 30 TC 8 Z9 8 U1 0 U2 1 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS JOHANNESBURG, SOUTH AFRICA SN 0038-2469 J9 S AFR MED J JI S. Afr. Med. J. PD DEC PY 1996 VL 86 IS 12 BP 1546 EP 1549 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VY130 UT WOS:A1996VY13000022 PM 8998225 ER PT J AU Liao, DP Cooper, L Cai, JW Toole, JF Bryan, NR Hutchinson, RG Tyroler, HA AF Liao, DP Cooper, L Cai, JW Toole, JF Bryan, NR Hutchinson, RG Tyroler, HA TI Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control - The ARIC study SO STROKE LA English DT Article DE epidemiology; ethnic groups; hypertension; white matter ID PERIVENTRICULAR LESIONS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ABNORMALITIES; ROTTERDAM; DECLINE; ADULTS; HEALTH; BRAIN; MRI AB Background and Purpose White matter lesions (WML) may result from cerebral hypoperfusion or ischemia. We investigated the association of WML with blood pressure, hypertension, and its treatment and control. Methods A random sample of 1920 participants aged 55 to 72 years in the Atherosclerosis Risk in Communities Study (ARIC) was examined. Spin-density 1.5-T MRI scan images were coded from 0 for normal to 9 for most severe WML. Hypertension was defined as systolic or diastolic pressure greater than or equal to 140/90 mm Hg or use of antihypertensive medication. Results The percentages of persons with WML grades 0 through 2 and 3 through 9, respectively, were as follows: normotensive, 92.4% and 7.6%, versus all hypertensive subjects, 83% and 17% (P<.001); and treated controlled hypertensive, 86% and 14%, versus treated uncontrolled hypertensive subjects, 76% and 24% (P=.003). Multivariable adjusted odds ratios (95% confidence intervals) for WML grade greater than or equal to 3 relative to normotensive subjects was 2.34 (1.71 to 3.20) for all hypertensives, 1.99 (1.19 to 3.08) for untreated hypertensives, 1.94 (1.32 to 2.85) for treated controlled hypertensives, and 3.40 (2.30 to 5.03) for treated uncontrolled hypertensives. After additional adjustment for hypertension duration, treatment, and control status, the odds ratios (95% confidence intervals) for a 1 SD increase of systolic and diastolic blood pressure were 1.43 (1.11 to 1.85) and 1.16 (0.94 to 1.43), respectively. Conclusions Hypertension is associated with increased odds of WML, and treated uncontrolled hypertensive subjects have greater odds of WML than those with treated controlled hypertension. The data suggest that the level of blood pressure, especially systolic blood pressure, is related to WML additional to the effects of categorically defined hypertension and its treatment and control status. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC 27514. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27103. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MISSISSIPPI,MED CTR,DEPT MED,JACKSON,MS 39216. RP Liao, DP (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,137 E FRANKLIN ST,NATIONSBANK PLAZA,SUITE 306,CHAPEL HILL,NC 27514, USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55019, N01-HC-55021] NR 20 TC 256 Z9 259 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1996 VL 27 IS 12 BP 2262 EP 2270 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VY009 UT WOS:A1996VY00900019 PM 8969791 ER PT J AU DOlhaberriague, L Litvan, I Mitsias, P Mansbach, HH AF DOlhaberriague, L Litvan, I Mitsias, P Mansbach, HH TI A reappraisal of reliability and validity studies in stroke SO STROKE LA English DT Article DE cerebrovascular disorders; epidemiology; stroke assessment; stroke classification ID ACUTE CEREBRAL INFARCTION; ADDITIONAL BASIC SCIENCE; ACUTE ISCHEMIC STROKE; CANADIAN NEUROLOGICAL SCALE; DATA-BANK; INTEROBSERVER AGREEMENT; CLINICAL MEDICINE; INTERRATER RELIABILITY; MAGNETIC-RESONANCE; KAPPA-COEFFICIENT AB Background The emergence of prophylactic and therapeutic interventions in stroke has been accompanied by the widespread use of stroke classifications and scales that measure deficit (stroke scales) or resulting long-term handicap (handicap and disability scales). Although the accuracy of some scales and classifications has been studied, there is no updated systematic review appraising all of them. Review We reviewed the literature and selected 21 studies on classifications and scales. The International Classification of Diseases, 10th revision, achieved the highest interobserver agreement among seven stroke classifications. The National Institutes of Health Stroke Scale, the Canadian Neurological Scale, and the European Stroke Scale had the highest reliability across items among nine stroke scales. The Barthel Index was the most reliable disability scale. Conclusions The identification of the most reliable stroke classifications and scales should encourage their use in selection of homogeneous populations of patients for clinical research studies and to improve communication among scientists. Further research is needed to investigate neglected aspects of the neurological examination and the validity of stroke classifications. C1 NINCDS,NEUROEPIDEMIOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RP DOlhaberriague, L (reprint author), HENRY FORD HOSP & HLTH SCI CTR,DEPT NEUROL,CTR STROKE RES,K-11,2799 W GRAND BLVD,DETROIT,MI 48202, USA. OI Litvan, Irene/0000-0002-3485-3445 FU NINDS NIH HHS [NS 23393] NR 83 TC 105 Z9 106 U1 2 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1996 VL 27 IS 12 BP 2331 EP 2336 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VY009 UT WOS:A1996VY00900038 PM 8969803 ER PT J AU Jaskowiak, NT Fraker, DL Alexander, HR Norton, JA Doppman, JL Jensen, RT AF Jaskowiak, NT Fraker, DL Alexander, HR Norton, JA Doppman, JL Jensen, RT TI Is reoperation for gastrinoma excision indicated in Zollinger-Ellison syndrome? SO SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 21-23, 1996 CL NAPA, CA SP Amer Assoc Endocrine Surgeons ID ENDOSCOPIC ULTRASONOGRAPHY; ENDOCRINE TUMORS; LOCALIZATION AB Background. Surgical excision of gastrinomas in patients with Zollinger-Ellison syndrome (ZES) decreases the incidence of hepatic metastases, but long-term biochemical cures are achieved in fewer than 30% of cases. A growing number of patients have persistent or recurrent disease after initial operation. The effect of reoperation in these patients has not been previously reported. Methods. From December 1982 to August 1995, 120 patients with ZES underwent operation for gastrinoma resection. Seventy-eight patients had recurrent or persistent ZES after operation; 17 patients underwent 18 reoperations. After initial operation all patients underwent yearly functional and imaging studies. If a tumor was unequivocally imaged, reexploration was done. Results. Five patients, all with sporadic disease, were disease free after operation, with a median follow-up of 28 months. Tumor was found in all 18 reoperations and resected in 17. In patients with continuing disease-free intervals, locations of gastrinomas included pancreatic head lymph nodes (three), liver metastasis (one), and pancreatic tail lymph node (one). There were no deaths in the cured group; two patients in the group with persistent disease have died (median follow-up, 34 months). Conclusions. Reoperation for gastrinoma excision resulted in elimination of disease in 30% of patients and should be considered for patients with imageable disease. C1 NIDDK,SURG METAB SECT,SURG BRANCH,NCI,DIGEST DIS BRANCH,BETHESDA,MD. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 24 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 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1996 VL 120 IS 6 BP 1055 EP 1062 DI 10.1016/S0039-6060(96)80055-9 PG 8 WC Surgery SC Surgery GA VW992 UT WOS:A1996VW99200046 PM 8957495 ER PT J AU Nelson, MA Thompson, FH Emerson, J Aickin, M Adair, L Trent, JM Leong, SPL Taetle, R AF Nelson, MA Thompson, FH Emerson, J Aickin, M Adair, L Trent, JM Leong, SPL Taetle, R TI Clinical implications of cytogenetic abnormalities in melanoma SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-MALIGNANT MELANOMA; FAMILIAL MELANOMA; NON-RANDOMNESS; P-VALUES; REGION; GENE; TRANSLOCATION; CELLS; P16; RET AB In contrast to leukemias, in which specific reciprocal translocations are observed frequently, melanomas are characterized by complex, recurring chromosome anomalies. Although methods for analyzing the clinical significance of chromosome abnormalities present significant problems, there are ongoing efforts to accomplish this task. the patterns of melanoma chromosome abnormalities may help to identify genes important in melanoma progression or pathogenesis. In the last 5 years, advances in genetic techniques have allowed the rapid identification and localization of melanoma-related genes, and the genes involved in melanoma pathogenesis are being localized and identified. Abnormalities of the cell cycle inhibitory protein P16 may be a critical event in the progression of both sporadic and familial melanoma. The identification and characterization of this gene now serve as a model for current and future gene-cloning efforts in melanoma. Genes associated with tumor behavior and survival in more advanced tumors may be sought in primary specimens, and they may provide increased information regarding patient populations likely to benefit from adjuvant or investigational therapies. C1 UNIV ARIZONA,ARIZONA CANC CTR,DEPT BIOMETRY,TUCSON,AZ 85724. UNIV ARIZONA,ARIZONA CANC CTR,CYTOGEN LAB,TUCSON,AZ 85724. NIH,DIV INTRAMURAL RES,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MT ZION CANC CTR,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. RP Nelson, MA (reprint author), UNIV ARIZONA,ARIZONA CANC CTR,DEPT PATHOL,ROOM 4921,1515 N CAMPBELL AVE,TUCSON,AZ 85724, USA. FU NCI NIH HHS [R29 CA70145-01, CA41183]; NHGRI NIH HHS [N01HG55390] NR 65 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD DEC PY 1996 VL 76 IS 6 BP 1257 EP & DI 10.1016/S0039-6109(05)70513-2 PG 16 WC Surgery SC Surgery GA WA772 UT WOS:A1996WA77200004 PM 8977549 ER PT J AU Boudoulas, S Lush, RM McCall, NA Samid, D Reed, E Figg, WD AF Boudoulas, S Lush, RM McCall, NA Samid, D Reed, E Figg, WD TI Plasma protein binding of phenylacetate and phenylbutyrate, two novel antineoplastic agents SO THERAPEUTIC DRUG MONITORING LA English DT Article DE phenylacetate; phenylbutyrate; protein binding; free fraction; dialysis; ultrafiltrate ID SERUM ALPHA-1-ACID GLYCOPROTEIN; PROSTATE-CANCER CELLS; PHASE-I; DIFFERENTIATION; METABOLITES; DRUGS; ACID AB Phenylacetate and phenylbutyrate, two novel inducers of tumor cytostasis and differentiation, are currently in clinical trials for the treatment of cancer in adults. The purpose of our study was to evaluate the plasma protein-binding characteristics of phenylacetate and phenylbutyrate in the plasma of normal volunteers and that of patients with cancer. Drug plasma protein-binding analysis was examined using three separate devices: a micropartition system and two equilibrium dialysis systems, all of which exhibited similar results. Phenylacetate and phenylbutyrate concentrations were determined by high-performance liquid chromatography. Both drugs exhibited concentration-dependent binding. Our results showed sodium phenylacetate to have a higher free fraction than sodium phenylbutyrate at corresponding concentrations (>0.442 +/- 0.008 and >0.188 +/- 0.001, respectively). Plasma pH did not greatly affect protein binding of either drug. As albumin concentration decreased, an increase in free fraction of both drugs was observed, however alpha(1)-acid glycoprotein showed no change in free fraction as its concentration increased. Patients with cancer with lower levels of albumin showed an increase in free fraction with both phenylacetate and phenylbutyrate. When phenylacetate and phenylbutyrate were added together in plasma, the free fraction of phenylacetate increased, whereas the phenylbutyrate free fraction slightly decreased. We conclude that phenylacetate and phenylbutyrate have high free fractions that change with varying albumin levels and when both phenylacetate and phenylbutyrate are present together in plasma. C1 NCI,CLIN PHARMACOL BRANCH,CLIN PHARMACOKINET SECT,NIH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 18 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 1996 VL 18 IS 6 BP 714 EP 720 DI 10.1097/00007691-199612000-00015 PG 7 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA VU911 UT WOS:A1996VU91100015 PM 8946671 ER PT J AU Benvenga, S Robbins, J AF Benvenga, S Robbins, J TI Altered thyroid hormone binding to plasma lipoproteins in hypothyroidism SO THYROID LA English DT Article ID APOLIPOPROTEIN-A-I; HIGH-DENSITY-LIPOPROTEINS; SUBCLINICAL HYPOTHYROIDISM; THYROXINE-BINDING; LDL RECEPTOR; CHOLESTEROL; THERAPY; FIBROBLASTS; DISEASE; PROTEIN AB Iodothyronine binding to plasma lipoproteins (Lp) and gel filtration elution patterns of cholesterol and triglycerides were evaluated in the total lipoprotein fractions (TLF) obtained from 10 healthy blood donors and 7 patients with hypothyroidism of brief duration, TLF (d < 1.210 kg/L) shown to be free of plasma T-4 transport proteins (TBG, TTR, HSA) was equilibrated with 0.3 nM I-125-labeled T-4, T-3 or reverse T-3 (rT(3)) and chromatographed on Sepharose CL-6B. Percent distribution of rT(3) among the Lp subtypes was similar in the two groups (in normals: VLDL = 4.2 +/- 2.4, LDL = 15.6 +/- 4.2, HDL = 79.9 +/- 5.2) but HDL in hypothyroid subjects bound significantly more T-4 (98.7 +/- 0.4 vs. 91.2 +/- 0.3%) and 4 (95.5 +/- 2.6 vs. 78.3 +/- 11.3%). Correspondingly less T-4 and T-3 was bound to VLDL and LDL. Whereas rT(3) elution coincided with the major HDL cholesterol peak (202 +/- 17 kDa) and was the same in the two groups, both T-4 and T-3 eluted with smaller HDL particles and differed between hypothyroid and normal subjects. T-4 eluted with somewhat larger HDL particles in hypothyroid subjects (176 +/- 24 kDa vs. 111 +/- 34 kDa) and T-3 eluted with smaller HDL (94 +/- 30 kDa vs. 148 +/- 31 kDa). The major HDL-cholesterol peak in hypothyroid subjects had a slightly but significantly greater mass than in normals (241 +/- 28 kDa vs. 218 +/- 14 kDa). The HDL elution patterns also differed: in normals there were from 3 to 6 minor peaks on either side of the major peak, whereas in hypothyroid subjects there were only 0 to 2 minor peaks. In conclusion, iodothyronines bind to relatively small size HDL subfractions and these are different for T-4, T-3, and rT(3); hypothyroidism of brief duration induces both quantitative and qualitative changes in iodothyronine distribution among lipoproteins and alters the microheterogeneity of HDL-cholesterol. C1 NIDDK,NIH,GBB,BETHESDA,MD 20892. NR 22 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 1996 VL 6 IS 6 BP 595 EP 600 DI 10.1089/thy.1996.6.595 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC354 UT WOS:A1996WC35400007 PM 9001194 ER PT J AU Sato, Y Ito, T Udaka, N Kanisawa, M Noguchi, Y Cushman, SW Satoh, S AF Sato, Y Ito, T Udaka, N Kanisawa, M Noguchi, Y Cushman, SW Satoh, S TI Immunohistochemical localization of facilitated-diffusion glucose transporters in rat pancreatic islets SO TISSUE & CELL LA English DT Article DE glucose transporter; immunohistochemistry; pancreas; islets of Langerhans; rat ID TISSUE DISTRIBUTION; GENE-EXPRESSION; FRUCTOSE TRANSPORTER; INSULIN RELEASE; SMALL-INTESTINE; MESSENGER-RNA; BETA-CELLS; SEQUENCE; BRAIN; LIVER AB The subcellular localization of five isoforms of facilitated-diffusion glucose transporters (GLUTs), from GLUT1 to GLUT5, in rat pancreatic islets was studied by immunohistochemistry using rabbit polyclonal antisera against mouse or rat GLUT peptides. Animals were perfusion-fixed with phosphate-buffered 4% paraformaldehyde and the pancreases were removed. Some specimens were embedded in paraffin, serially sectioned, and immunostained for glucagon, insulin, somatostatin, and the GLUTs for light microscopic observation. Others were prepared for immunoelectron microscopy by the post-embedding method. By these methods, GLUT2 immunostaining was observed on the lateral membranes of pancreatic beta-cells, whereas GLUT3 immunoreaction was predominantly localized in the cytoplasm of beta-cells and was not found in alpha-cells. In contrast, GLUT5 immunostaining was preferentially localized in the cytoplasm of alpha-cells compared to that of beta-cells. However, GLUT1 and GLUT4 were either barely or not at all detectable in any cells. These results suggest that rat islets take up glucose by at least three different processes and that blood glucose levels could be modulated differentially by: a high Km glucose transporter, GLUT2, in beta-cells; by a low Km glucose transporter, GLUT3, in beta-cells; and by a low Km glucose transporter, GLUT5, in alpha-cells. C1 YOKOHAMA CITY UNIV,SCH MED,DEPT PATHOL,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT SURG,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT INTERNAL MED,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD. NR 37 TC 39 Z9 41 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD DEC PY 1996 VL 28 IS 6 BP 637 EP 643 DI 10.1016/S0040-8166(96)80067-X PG 7 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA WA721 UT WOS:A1996WA72100002 PM 9004533 ER PT J AU Schuck, P Minton, AP AF Schuck, P Minton, AP TI Kinetic analysis of biosensor data: Elementary tests for self consistency SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID BINDING CONSTANTS; PLASMON RESONANCE; SH2 DOMAINS; RECEPTOR; SURFACE AB The validity of the most common kinetic interpretation of biosensor data can be quickly assessed with the aid of two simple tests for self-consistency, requiring only back-of-the-envelope calculations. A search of the recent literature reveals that many published results fail these tests qualitatively. RP Schuck, P (reprint author), NIDDKD,SECT PHYS BIOCHEM,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892, USA. OI Schuck, Peter/0000-0002-8859-6966 NR 18 TC 116 Z9 116 U1 1 U2 5 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 DEC PY 1996 VL 21 IS 12 BP 458 EP 460 DI 10.1016/S0968-0004(96)20025-8 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ805 UT WOS:A1996VZ80500002 PM 9009825 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Expression profiling using messenger RNA assays 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 use of hybridization techniques for the quantitation of gene expression and a contaminant found when isolating His-tagged proteins. 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 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1996 VL 21 IS 12 BP 492 EP 493 DI 10.1016/S0968-0004(96)30045-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ805 UT WOS:A1996VZ80500012 PM 9009834 ER PT J AU Stojilkovic, SS AF Stojilkovic, SS TI Special section on calcium signaling in pituitary cells SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Editorial Material ID GROWTH-HORMONE SECRETION; INTRACELLULAR CALCIUM; PROLACTIN SECRETION; CYTOSOLIC CALCIUM; ACTION-POTENTIALS; OSCILLATIONS; GONADOTROPHS; CHANNELS; SOMATOSTATIN; MECHANISM RP Stojilkovic, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. NR 40 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 1996 VL 7 IS 10 BP 357 EP 360 DI 10.1016/S1043-2760(96)00190-7 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY075 UT WOS:A1996VY07500001 PM 18406771 ER PT J AU Stojilkovic, SS Tomic, M AF Stojilkovic, SS Tomic, M TI GnRH-induced calcium and current oscillations in gonadotrophs SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID LUTEINIZING-HORMONE SECRETION; PITUITARY GONADOTROPHS; CA2+ OSCILLATIONS; ENDOPLASMIC-RETICULUM; LAEVIS OOCYTES; ACINAR-CELLS; CHANNELS; EXCITABILITY; MODULATION; FREQUENCY AB The rat pituitary gonadotroph is a well-studied cell model for investigation of the oscillatory nature of calcium signaling in agonist-stimulated excitable cells. Cytosolic calcium levels [Ca2+](i)) in gonadotrophs are controlled by two distinct oscillators, a plasma membrane oscillator that generates extracellular calcium-dependent low-amplitude [Ca2+](i) spiking in unstimulated cells and an endoplasmic reticulum oscillator that is activated by calcium-mobilizing receptors for GnRH, endothelin, and pituitary adenylate cyclase-activating polypeptide. In this review, the characteristics of the spontaneous and agonist-induced calcium oscillations in gonadotrophs and the coordinate actions of the two oscillators during GnRH action are discussed. (C) 1996, Elsevier Science Inc. RP Stojilkovic, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892, USA. RI Tomic, Melanija/C-3371-2016 NR 33 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 1996 VL 7 IS 10 BP 379 EP 384 DI 10.1016/S1043-2760(96)00189-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY075 UT WOS:A1996VY07500006 PM 18406776 ER PT J AU Rinzel, J Keizer, J Li, YX AF Rinzel, J Keizer, J Li, YX TI Modeling plasma membrane and endoplasmic reticulum excitability in pituitary cells SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CALCIUM OSCILLATIONS; INOSITOL TRISPHOSPHATE; GONADOTROPHS; CA2+; RECEPTOR; RELEASE AB The response of gonadotrophs to secretagogues involves dose-dependent, complex dynamic patterns of electrical activity and inositol 1,4,5-trisphosphate (InsP(3))-induced Ca2+ mobilization, including pulsatility and oscillations on multiple time scales from milliseconds to minutes. Detailed in vitro experiments have enabled the identification of key mechanisms that underlie the plasma membrane (PM) electrical excitability and endoplasmic reticulum (ER) calcium excitability. We summarize these findings and review computer simulations of a biophysical model that resynthesizes and couples these components and that reproduces quantitatively the observed time courses and dose-response characteristics, as well as effects of various pharamacological manipulations. The theory suggests that cytosolic calcium is the primary messenger in coordinating the PM and ER regenerative behaviors during ER depletion and refilling. (C) 1996, Elsevier Science Inc. C1 UNIV CALIF DAVIS,INST THEORET DYNAM,SECT NEUROBIOL PHYSIOL & BEHAV,DAVIS,CA 95616. RP Rinzel, J (reprint author), NIDDK,MATH RES BRANCH,NIH,BETHESDA,MD 20892, USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 1996 VL 7 IS 10 BP 388 EP 393 DI 10.1016/S1043-2760(96)00194-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY075 UT WOS:A1996VY07500008 PM 18406778 ER PT J AU Kostenis, E Mohr, K AF Kostenis, E Mohr, K TI Quantitation of allosteric interactions - Reply SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Letter ID MUSCARINIC RECEPTORS; MODULATORS; LIGANDS C1 UNIV BONN,DEPT PHARMACOL & TOXICOL,INST PHARMACOL,D-53121 BONN,GERMANY. RP Kostenis, E (reprint author), NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 8 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD DEC PY 1996 VL 17 IS 12 BP 443 EP 444 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC805 UT WOS:A1996WC80500005 ER PT J AU Francois, G Bringmann, G Boyd, MR Holenz, J Timperman, G Steenackers, T vanLooveren, M Assi, LA AF Francois, G Bringmann, G Boyd, MR Holenz, J Timperman, G Steenackers, T vanLooveren, M Assi, LA TI New and highly efficient drugs against malaria: The naphthylisoquinoline alkaloids. SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article C1 UNIV WURZBURG,INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. NCI,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. UNIV ABIDJAN,CTR NATL FLORIST,ABIDJAN 08,COTE IVOIRE. RP Francois, G (reprint author), INST TROP MED PRINCE LEOPOLD,NATL STR 155,B-2000 ANTWERP,BELGIUM. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD DEC PY 1996 VL 1 IS 6 BP A29 EP A29 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA VZ213 UT WOS:A1996VZ21300037 ER PT J AU Pearson, JD Luderer, AA Metter, EJ Partin, AW Chan, DW Fozard, JL Carter, HB AF Pearson, JD Luderer, AA Metter, EJ Partin, AW Chan, DW Fozard, JL Carter, HB TI Longitudinal analysis of serial measurements of free and total psa among men with and without prostatic cancer SO UROLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the American-Urological-Association CY MAY 04-09, 1996 CL ORLANDO, FL SP Amer Urol Assoc ID ANTIGEN; SERUM; ALPHA-1-ANTICHYMOTRYPSIN; COMPLEX AB Objectives. Evaluation of free and total serum prostate specific antigen [PSA) levels before diagnosis of prostate cancer. Methods. Free and total PSA levels were measured on frozen sera samples of 26 men with no history of prostate disease (controls), 29 men with a histologic diagnosis of benign prostatic hyperplasia (BPH) made at simple prostatectomy (BPH cases), and 23 men with a histologic diagnosis of prostatic cancer (cancer cases). Longitudinal regression analysis was used to evaluate PSA levels as a function of years before diagnosis of prostate disease. Results. On average, mean total serum PSA was statistically significantly greater for subjects with cancer (5.0 ng/mL +/- 0.9) Versus BPH (2.8 ng/mL +/- 0.3) and control subjects (0.8 ng/mL +/- 0.1) by 4 years before diagnosis, whereas free PSA levels were similar among groups at 4 years before diagnosis. The ratio of free to total serum PSA continuously decreased among cancer cases over the decade before cancer diagnosis. At a time when mean total and free PSA levels were similar among groups (8 years before diagnosis), the ratio of free to total PSA was statistically significantly lower for cancer cases (0.13 +/- 0.01] compared with BPH (0.17 +/- 0.01) and control cases (0.21 +/- 0.02), Use of a free to total PSA ratio of less than or equal to 0.12 when total PSA was between 4.0 and 10.0 ng/mL resulted in the highest sensitivity (76%) and specificity (94%) for diagnosis among subjects with and without cancer. Lowering the reflex range to 2.5 ng/mL increased false positive tests more than it increased sensitivity. Conclusions. The ratio of free to total PSA is the earliest serum marker predicting a subsequent diagnosis of prostate cancer. Measurement of the free to total serum PSA ratio would appear to reduce false positive results among men without prostate cancer. Copyright 1996 by Elsevier Science Inc. C1 JOHNS HOPKINS UNIV HOSP, DEPT UROL, JAMES BUCHANAN BRADY UROL INST, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT UROL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21218 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. MERCK RES LABS, DEPT EPIDEMIOL, BLUE BELL, PA USA. DIANON SYST INC, DEPT RES & DEV, STRATFORD, CT USA. RI Fozard, James Leonard/B-3660-2009 NR 11 TC 48 Z9 48 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD DEC PY 1996 VL 48 IS 6A SU S BP 4 EP 9 DI 10.1016/S0090-4295(96)00603-6 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA WA648 UT WOS:A1996WA64800002 PM 8973693 ER PT J AU Lee, SM Son, HG Lee, YS Lee, KS Rhee, SG Cho, KS AF Lee, SM Son, HG Lee, YS Lee, KS Rhee, SG Cho, KS TI Purification and characterization of membrane-bound phosphatidylinositol 4-kinase from mouse brain SO JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE enzyme purification; mouse brain; phosphatidylinositol 4-kinase ID PHOSPHOLIPASE-C ENZYMES; PROTEIN KINASE-C; SACCHAROMYCES-CEREVISIAE; 2ND MESSENGERS; BOVINE BRAIN; POLYACRYLAMIDE GELS; KINETIC-ANALYSIS; TRITON X-100; DIACYLGLYCEROL; ACTIVATION AB A membrane-bound phosphatidylinositol 4-kinase (PI4-kinase) was separated in a sucrose gradient and solubilized with 1% Triton X-100 from mouse brain. The enzyme was purified 2,952-fold by various chromatographic techniques including DEAE-cellulose, PI-Sepharose and Sephacryl S-200 gel filtration. The molecular weight of PI 4-kinase was approximately 76 kDa by gel filtration and 70.8 kDa by SDS-polyacrylamide gel electrophoresis. The purified enzyme exhibited specific activity of 11.2 nmol/min/mg protein and pi value of 4.7. Kinetic analysis of the PI 4-kinase indicated apparent K-m values of 190 mu M and 120 mu M for phosphatidylinositol and ATP, respectively. The maximal activity of this purified enzyme was observed at pH 7.4 at an incubation temperature of 37 degrees C. The enzyme activity was significantly activated by Mg2+, Mn2+ and Fe2+, and inhibited severely by Ca2+. PI 4-kinase was proved to be pure in its immunoblot test by polyclonal antibody prepared from immunized rabbit sera. By this test, we were able to detect the existence of the same type of PI 4-kinase from other mouse organ tissues, such as liver, heart, kidney and spleen. Furthermore, similar immunoblot analysis with the same antisera recognized the different epitopes of PI 4-kinase proteins from various organs of rabbit chinese hamster and rat. C1 HANYANG UNIV,COLL SCI,DEPT BIOCHEM & MOL BIOL,ANSHAN 425791,PEOPLES R CHINA. KOREA ATOM ENERGY RES INST,RADIAT BIOL LAB,TAEJON 305353,SOUTH KOREA. NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 34 TC 1 Z9 1 U1 0 U2 1 PU BIOCHEMICAL SOC REPUBLIC KOREA PI SEOUL PA 538 DOWHA-DONG, SUNG-JEE BLDG B705, MAPO-KU, SEOUL 121-743, SOUTH KOREA SN 1225-8687 J9 J BIOCHEM MOL BIOL JI J. Biochem. Mol. Biol. PD NOV 30 PY 1996 VL 29 IS 6 BP 555 EP 563 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VX281 UT WOS:A1996VX28100013 ER PT J AU Cunnion, RE Masur, H AF Cunnion, RE Masur, H TI Physician staffing in intensive-care units SO LANCET LA English DT Editorial Material ID IMPACT RP Cunnion, RE (reprint author), NATL INST HLTH,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 5 TC 6 Z9 6 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 NOV 30 PY 1996 VL 348 IS 9040 BP 1464 EP 1465 DI 10.1016/S0140-6736(05)65887-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VV463 UT WOS:A1996VV46300004 PM 8942771 ER PT J AU States, JC Reed, E AF States, JC Reed, E TI Enhanced XPA mRNA levels in cisplatin-resistant human ovarian cancer are not associated with XPA mutations or gene amplification SO CANCER LETTERS LA English DT Article DE XPA; ovarian cancer; chemoresistance; cisplatin; DNA repair; gene expression ID DNA-REPAIR; EXCISION-REPAIR; ERCC1; CHEMOTHERAPY; DAMAGE AB Enhanced expression of the nucleotide excision repair gene XPA is associated with resistance to cisplatin treatment in human ovarian cancer. Understanding the cause of enhanced XPA expression will provide new molecular targets for therapy directed at overcoming chemoresistance. Enhanced gene expression in cancer cells is often caused by mutations or gene amplification. Molecular analyses of the XPA genes in human ovarian cancers indicate that gene mutation and amplification are not the cause of enhanced XPA mRNA levels in ovarian cancers overexpressing XPA. Altered nucleotide excision repair (NER) gene regulation in chemoresistant tumors is discussed. C1 NCI,CLIN PHARMACOL BRANCH,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. RP States, JC (reprint author), WAYNE STATE UNIV,CTR MOL MED & GENET,DETROIT,MI, USA. RI States, J./H-4246-2011 NR 15 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 29 PY 1996 VL 108 IS 2 BP 233 EP 237 DI 10.1016/S0304-3835(96)04428-X PG 5 WC Oncology SC Oncology GA VW448 UT WOS:A1996VW44800013 PM 8973600 ER PT J AU King, RA BanikMaiti, S Jin, DJ Weisberg, RA AF King, RA BanikMaiti, S Jin, DJ Weisberg, RA TI Transcripts that increase the processivity and elongation rate of RNA polymerase SO CELL LA English DT Article ID ESCHERICHIA-COLI RNA; TERMINATION EFFICIENCY; PHAGE-LAMBDA; PAUSE SITE; ANTITERMINATION; PROTEIN; RHO; PHAGE-HK022; PROMOTERS; HAIRPIN AB Transcripts encoded by the cis-acting antitermination sites (put sites) of lambdoid phage HK022 promote readthrough of downstream transcription terminators. Proper conformation of the transcripts is essential for activity, since put mutations that prevent the formation of predicted RNA stems prevented antitermination, and suppressor mutations that restore the stems restored antitermination. Antitermination does not appear to require proteins other than RNA polymerase, since put-dependent readthrough of multiple sequential terminators was observed in a purified transcription system consisting of template, polymerase, substrates, and buffer. Transcription of put also increased the elongation rate of polymerase, very likely by suppressing pausing. A mutation that alters the zinc-finger region of the beta' subunit of polymerase specifically prevented the put-dependent increases in terminator readthrough and elongation rate. The simplicity of HK022 antitermination contrasts with that of other known antitermination pathways. We propose that the central effector is a transcript that directly alters the elongation properties of RNA polymerase. C1 NICHHD,SECT MICROBIAL GENET,GENET MOL LAB,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 36 TC 37 Z9 37 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 29 PY 1996 VL 87 IS 5 BP 893 EP 903 DI 10.1016/S0092-8674(00)81996-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VV774 UT WOS:A1996VV77400015 PM 8945516 ER PT J AU Ogryzko, VV Schiltz, RL Russanova, V Howard, BH Nakatani, Y AF Ogryzko, VV Schiltz, RL Russanova, V Howard, BH Nakatani, Y TI The transcriptional coactivators p300 and CBP are histone acetyltransferases SO CELL LA English DT Article ID NUCLEAR-PROTEIN CBP; E1A; SEQUENCE; CREB; DNA; NUCLEOSOME; ALIGNMENT; ADAPTER; FAMILY AB p300/CBP is a transcriptional adaptor that integrates signals from many sequence-specific activators via direct interactions. Various cellular and viral factors target p300/CBP to modulate transcription and/or cell cycle progression. One such factor, the cellular p300/CBP associated factor (PCAF), possesses intrinsic histone acetyltransferase activity. Here, we demonstrate that p300/CBP is not only a transcriptional adaptor but also a histone acetyltransferase. p300/CBP represents a novel class of acetyltransferases in that it does not have the conserved motif found among various other acetyltransferases. p300/CBP acetylates all four core histones in nucleosomes. These observations suggest that p300/CBP acetylates nucleosomes in concert with PCAF. RP Ogryzko, VV (reprint author), NICHHD,LAB MOL GROWTH REPROD,NIH,BETHESDA,MD 20892, USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 42 TC 2026 Z9 2054 U1 8 U2 69 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 29 PY 1996 VL 87 IS 5 BP 953 EP 959 DI 10.1016/S0092-8674(00)82001-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VV774 UT WOS:A1996VV77400020 PM 8945521 ER PT J AU Szapary, D Xu, M Simons, SS AF Szapary, D Xu, M Simons, SS TI Induction properties of a transiently transfected glucocorticoid-responsive gene vary with glucocorticoid receptor concentration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE AMINOTRANSFERASE GENE; PROTEIN-PROTEIN INTERACTIONS; HUMAN PROGESTERONE-RECEPTOR; THYROID-HORMONE RECEPTOR; HUMAN ESTROGEN-RECEPTOR; TRANSCRIPTIONAL ACTIVATION FUNCTIONS; DNA-BINDING; DEXAMETHASONE 21-MESYLATE; NUCLEAR-LOCALIZATION; STEROID-RECEPTORS AB Transient transfections of steroid receptors have yielded much of the data used to construct the current models of steroid hormone action, These experiments invariably examine the ability of receptors to regulate transcription when occupied by saturating concentrations of steroid, We now report that other induction properties of a transiently transfected gene are not constant but vary with the concentration of transiently transfected glucocorticoid receptors, Thus, the percentage of maximal induction seen with subsaturating concentrations of glucocorticoid could be dramatically increased, and an antiglucocorticoid could be converted into a partial glucocorticoid, simply by increasing the concentration of glucocorticoid receptors. This behavior was observed in HeLa cells, containing endogenous receptors, or in CV-1 cells, containing almost no endogenous receptor, with either homologous or heterologous receptors, These increases were relatively insensitive to the concentration of reporter gene, suggesting the titration of some transcription factor(s) involved in regulating the position of the glucocorticoid dose-response curve and the agonist activity of an antiglucocorticoid. This property of transfected glucocorticoid receptors required a full-length, functionally active receptor but was retained, albeit reduced in magnitude, in the absence of binding to a glucocorticoid response element, Furthermore, this phenomenon was specific in that the A form of the human progesterone receptor had no effect under the same conditions, These variations in induction properties of antiglucocorticoids and of subsaturating concentrations of glucocorticoid, in a manner that was proportional to the amount of transfected receptor, reveal processes that are not operative with saturating concentrations of glucocorticoid. These variations also demonstrate that caution should be exercised in making mechanistic conclusions based solely on experiments conducted with saturating concentrations of glucocorticoid. C1 NIDDK,STEROID HORMONES SECT,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. NR 61 TC 68 Z9 68 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 NOV 29 PY 1996 VL 271 IS 48 BP 30576 EP 30582 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800046 PM 8940029 ER PT J AU Qian, SW Burmester, JK Tsang, MLS Weatherbee, JA Hinck, AP Ohlsen, DJ Sporn, MB Roberts, AB AF Qian, SW Burmester, JK Tsang, MLS Weatherbee, JA Hinck, AP Ohlsen, DJ Sporn, MB Roberts, AB TI Binding affinity of transforming growth factor-beta for its type II receptor is determined by the C-terminal region of the molecule SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; HUMAN ENDOTHELIAL-CELLS; EXPRESSION CLONING; CRYSTAL-STRUCTURE; 2 FORMS; ENDOGLIN; PROTEIN; SYSTEM; COMPLEX; LINES AB Transforming growth factor-beta (TGF-beta) isoforms have differential binding affinities for the TGF-beta type II receptor (T beta RII). In most cells, TGF-beta 1 and TGF-beta 3 bind to T beta RII with much higher affinity than TGF-beta 2. Here, we report an analysis of the effect of TGF-beta structure on its binding to T beta RII by using TGF-beta mutants with domain deletions, amino acid replacements, and isoform chimeras, Examination of the binding of TGF-beta mutants to the recombinant extracellular domain of T beta RII by a solid-phase TGF-beta/T beta RII assay demonstrated that only those TGF-beta mutants containing the C terminus of TGF-beta 1 (TGF-beta 1-(Delta 69-73), TGF-beta 1-(Trp(71)), and TGF-beta 2/beta 1-(83-112)) bind with high affinity to T beta RII, similar to native TGF-beta 1. Moreover, replacement of only 6 amino acids in the C terminus of TGF-beta 1 with the corresponding sequence of TGF-beta 2 (TGF-beta 1/beta 2-(91-96)) completely eliminated the high affinity binding of TGF-beta 1. Proliferation of fetal bovine heart endothelial (FBHE) cells was inhibited to a similar degree by all of the TGF-beta mutants. However, recombinant soluble T beta RII blocked the inhibition of FBHE cell proliferation induced by TGF-beta mutants retaining the C terminus of TGF-beta 1, consistent with the high binding affinity between these TGF-beta molecules and T beta RII, It was further confirmed that the TGF-beta 2 mutant with its C terminus replaced by that of TGF-beta 1 (TGF-beta 2/beta 1-(83-112)) competed as effectively as TGF-beta 1 with I-125-TGF-beta 1 for binding to membrane T beta RI and T beta RII on FBHE cells. These observations clearly indicate that the domain in TGF-beta 1 responsible for its high affinity binding to T beta RII, both the soluble and membrane-bound forms, is located at C terminus of the molecule. C1 NCI,NIH,CHEMOPREVENT LAB,BETHESDA,MD 20892. MARSHFIELD MED RES FDN,MARSHFIELD,WI 54449. R&D SYST,MINNEAPOLIS,MN 55413. NIDR,NIH,STRUCT MOL BIOL UNIT,BETHESDA,MD 20892. NR 54 TC 50 Z9 50 U1 0 U2 2 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 NOV 29 PY 1996 VL 271 IS 48 BP 30656 EP 30662 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800058 PM 8940041 ER PT J AU Tarcsa, E Marekov, LN Mei, G Melino, G Lee, SC Steinert, PM AF Tarcsa, E Marekov, LN Mei, G Melino, G Lee, SC Steinert, PM TI Protein unfolding by peptidylarginine deiminase - Substrate specificity and structural relationships of the natural substrates trichohyalin and filaggrin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM DODECYL-SULFATE; CORNIFIED CELL-ENVELOPE; INTERMEDIATE FILAMENTS; GEL-ELECTROPHORESIS; HAIR FOLLICLE; MOLECULAR-CLONING; ARGININE RESIDUE; SKELETAL-MUSCLE; MOUSE; PURIFICATION AB Peptidylarginine deiminases, which are commonly found in mammalian cells, catalyze the deimination of protein-bound arginine residues to citrullines. However, very little is known about their substrate requirements and the significance or consequences of this postsynthetic modification. We have explored this reaction in vitro with two known substrates filaggrin and trichohyalin. First, the degree and rate of modification of arginines to citrullines directly correlates with the structural order of the substrate. In filaggrin, which has little structural order, the reaction proceeded rapidly to >95% completion. However, in the highly a-helical protein trichohyalin, the reaction proceeded slowly to about 25% and could be forced to a maximum of about 65%. Second, the rate and degree of modification depends on the sequence location of the target arginines. Third, we show by gel electrophoresis, circular dichroism, and fluorescence spectroscopy that the reaction interferes with organized protein structure: the net formation of greater than or equal to 10% citrulline results in protein denaturation. Cyanate modification of the lysines in model alpha-helix-rich proteins to homocitrullines also results in loss of organized structure. These data suggest that the ureido group on the citrulline formed by the peptidylarginine deiminase enzyme modification functions to unfold proteins due to decrease in net charge, loss of potential ionic bonds, and interference with H bonds. C1 NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,IST DERMOPAT IMMACOLATA,BIOCHEM LABS,DEPT EXPT MED & BIOCHEM SCI,I-00133 ROME,ITALY. UNIV AQUILA,DEPT BIOL,I-67100 LAQUILA,ITALY. NR 59 TC 184 Z9 191 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 1996 VL 271 IS 48 BP 30709 EP 30716 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800065 PM 8940048 ER PT J AU Jubete, Y Maurizi, MR Gottesman, S AF Jubete, Y Maurizi, MR Gottesman, S TI Role of the heat shock protein DnaJ in the Lon-dependent degradation of naturally unstable proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; FUSION PROTEIN; ION GENE; LAMBDA-N; PROTEOLYSIS; CHAPERONE; MUTANTS; GRPE; SULA; PURIFICATION AB We have investigated the role of DnaJ in protein degradation by examining the degradation of intrinsically unstable proteins by Lon protease in vivo. In Escherichia coli, Lon protease is responsible for the rate-limiting step in degradation of highly unstable proteins such as SulA, RcsA, and lambda N protein, as well as for about 50% of the rapid degradation of abnormal proteins such as canavanine-containing proteins. We found that Lon-dependent degradation of both SulA and AN protein was unaffected in cells lacking functional DnaJ, whereas Lon-dependent turnover of canavanine containing proteins was slower in dnaJ mutant cells. DnaJ also affected the slow SulA degradation seen in the absence of Lon. The rate of degradation of RcsA was reduced in dnaJ mutants, but both Lon-dependent and Lon-independent degradation was affected; abnormal, canavanine-containing proteins were similarly affected. Both the RcsA that accumulated in dnaJ mutant cells and the SulA that accumulated in ion dnaJ mutant cells was aggregated. The abnormal proteins that partitioned to the insoluble pellet became solubilized over time in dnaJ(+) cells but not in dnaJ(-) cells. Therefore, the co-chaperone DnaJ is not essential for Lon-dependent degradation and may act in protein turnover only as an accessory factor helping to maintain substrates in a soluble form. Such an accessory factor is apparently necessary for abnormal proteins and for RcsA. The relative rates of degradation and aggregation of specific protein targets may determine the importance of the chaperone systems in turnover of a given protein. C1 NCI, MOL BIOL LAB, BETHESDA, MD 20892 USA. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. NR 45 TC 56 Z9 58 U1 0 U2 5 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 NOV 29 PY 1996 VL 271 IS 48 BP 30798 EP 30803 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800077 PM 8940060 ER PT J AU Meric, F Searfoss, AM Wormington, M Wolffe, AP AF Meric, F Searfoss, AM Wormington, M Wolffe, AP TI Masking and unmasking maternal mRNA - The role of polyadenylation, transcription, splicing, and nuclear history SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS OOCYTE MATURATION; MESSENGER-RIBONUCLEOPROTEIN PARTICLES; ACID BINDING-PROTEINS; CYTOPLASMIC POLYADENYLATION; TRANSLATIONAL REGULATION; POLY(A) POLYMERASE; RNA TRANSLATION; SOMATIC-CELLS; FROG OOCYTES; 3' UTR AB We establish that masked mRNAs synthesized from exogenous plasmid templates microinjected into the nuclei of Xenopus oocytes are translationally activated (unmasked) on oocyte maturation concomitant with polyadenylation. Synthetic mRNA injected into the cytoplasm of the oocyte is translated over an order of magnitude more efficiently than is the cognate mRNA synthesized in vivo. Both mRNA synthesized in vivo and mRNA microinjected into the oocyte cytoplasm require a cytoplasmic polyadenylation element in the 3'-untranslated region to activate translation on maturation. Although polyadenylation upon oocyte maturation can relieve the translational repression of mRNA synthesized in vivo, the excision of an intron within the nucleus does not relieve repression. We suggest that the translational repression coupled to the transcription process will more effectively repress inappropriate gene expression in the oocyte and offer the potential to achieve a wider range of gene regulation. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT BIOL,CHARLOTTESVILLE,VA 22903. FU NICHD NIH HHS [R01 HD 17691] NR 48 TC 31 Z9 31 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 NOV 29 PY 1996 VL 271 IS 48 BP 30804 EP 30810 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800078 PM 8940061 ER PT J AU Vance, BA Zacharchuk, CM Segal, DM AF Vance, BA Zacharchuk, CM Segal, DM TI Recombinant mouse Bcl-2((1-203)) - Two domains connected by a long protease-sensitive linker SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; BCL-2 GENE; CONSERVED DOMAINS; INDUCED APOPTOSIS; BAX; HETERODIMERIZATION; BCL-2-ALPHA; PROTEINS; FAMILY; BH1 AB Bcl-2 is a cytoplasmic integral membrane protein with potent anti-apoptotic activity but whose mechanism of action is poorly understood. The purpose of this paper was to obtain large amounts of soluble Bcl-2 protein for structural and functional studies. Mouse Bcl-2((1-203)) (missing the COOH-terminal hydrophobic tail) was produced in bacterial inclusion bodies, solubilized in guanidine, and refolded by dialysis. The resulting protein was monomeric in nondenaturing solution and was active in protecting mouse T hybridoma cells from glucocorticoid-induced apoptosis. Refolded Bcl-2((1-203)) showed no tendency to homodimerize by gel filtration or analytical ultracentrifugation. Limited proteolysis experiments identified a region between the BH3 and BH4 homology domains of Bcl-2((1-203)) which was extremely susceptible to digestion by several common proteases, but not by a cell extract known to contain CPP-32-like (interleukin-1 beta-converting enzyme family) protease activity. The protease-sensitive sites were located within a 50-residue stretch that contained most of the nonconserved and proline residues of Bcl-2((1-203)). Trypsin-cleaved Bcl-2((1-203)) eluted in the same position as the undigested protein on gel filtration in nondenaturing solution, indicating that the two portions of the molecule connected by the protease-sensitive region associate stably and noncovalently. The solution properties of Bcl-2((1-203)) suggest that it consists of two noncovalently associated domains connected by a long protease-sensitive linker and that its structure is similar to that of Bcl-x(L), which has been determined by x-ray and NMR analysis. C1 NCI,NIH,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,NIH,LAB IMMUNE CELL BIOL,BETHESDA,MD 20892. NR 25 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 1996 VL 271 IS 48 BP 30811 EP 30815 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800079 PM 8940062 ER PT J AU Tanimura, A Turner, RJ AF Tanimura, A Turner, RJ TI Inositol 1,4,5-trisphosphate-dependent oscillations of luminal [Ca2+] in permeabilized HSY cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM OSCILLATIONS; FLUORESCENT INDICATOR; INTRACELLULAR STORES; RELEASE; TRISPHOSPHATE; STIMULATION; HEPATOCYTES; CHANNELS; KINASE; WAVES AB Oscillations in intracellular Ca2+ concentration ([Ca2+](i)) are thought to play an important role in phosphoinositide-linked Ca2+ signaling events, We demonstrate corresponding inositol 1,4,5-trisphosphate (IP3) dependent oscillations of Ca2+ concentration within the lumen of the IP3-sensitive stores ([Ca2+](L)) of saponin-permeabilized HSY cells by monitoring [Ca2+](L) with the fluorescent Ca2+ indicator Mag-fura-a, The associated openings and closings of the IP3-sensitive Ca2+ release channel were detected via quenching of Mag-fura-a fluorescence due to the entry of Mn2+, a Ca2+ surrogate, into the stores, Evidence for complimentary Ca2+ oscillations at the external surface of the stores was provided by the membrane-bound Ca2+ probe Calcium Green C-18. The permeabilization of saponin-treated HSY cells to macromolecules was confirmed by demonstrating that permeabilized cells readily took up and lost (t(1/2) approximate to 46 s) a fluorescently tagged 70-kDa dextran. Our results impose a number of constraints on possible mechanisms for [Ca2+](i) oscillations. In addition, they support recent proposals that [Ca2+](i) oscillations arise directly from the (biphasic) effects of Ca2+ itself on IP3-sensitive Ca2+ channel activity. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. HLTH SCI UNIV HOKKAIDO,DEPT DENT PHARMACOL,ISHIKARI,HOKKAIDO 06102,JAPAN. NR 24 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 1996 VL 271 IS 48 BP 30904 EP 30908 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800092 PM 8940075 ER PT J AU Murphy, C Nikodem, D Howcroft, K Weissman, JD Singer, DS AF Murphy, C Nikodem, D Howcroft, K Weissman, JD Singer, DS TI Active repression of major histocompatibility complex class I genes in a human neuroblastoma cell line SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-I; NF-KAPPA-B; EXPRESSION; BETA-2-MICROGLOBULIN; ANTIGENS; INTERFERON; SEQUENCES; ENHANCER; PROMOTER; DNA AB Human neuronal cells express neither major histocompatibility complex (MHC) class I RNA nor cell surface molecules but can be induced to do so by various cytokines, In the present studies, we report that expression of MHC class I in a neuroblastoma cell line, CHP-126, is actively repressed. This repression is mediated by the combined effects of a series of upstream silencer elements. Removal of the silencers reveals not only an active promoter element but also the presence of an active enhancer, Four silencers have been identified and shown to have distinct sequences, binding factors, and patterns of function, One element is located between -724 and -697 base pairs (bp) and corresponds to a silencer involved in tissue-specific regulation of class I gene expression. Three additional elements occur between -503 and -402 bp, One of these corresponds to a c-jun, responsive element. Neither of the remaining elements corresponds to DNA sequences known to regulate expression of other genes, These data demonstrate that MHC class I expression normally is actively repressed in neuronal cells and suggest a model of rapid and specific triggering of class I in neuronal cells in response to infection. C1 NCI,EXPT IMMUNOL BRANCH,DBS,NIH,BETHESDA,MD 20892. NR 23 TC 28 Z9 28 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 NOV 29 PY 1996 VL 271 IS 48 BP 30992 EP 30999 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV158 UT WOS:A1996VV15800105 PM 8940088 ER PT J AU Boal, JH Wilk, A Scremin, CL Gray, GN Phillips, LR Beaucage, SL AF Boal, JH Wilk, A Scremin, CL Gray, GN Phillips, LR Beaucage, SL TI Synthesis of (2-deoxy-alpha- and -beta-D-erythro-pentofuranosyl)(thymin-1-yl)alkanes and their incorporation into oligodeoxyribonucleotides. Effect of nucleobase-sugar linker flexibility on the formation of DNA-DNA and DNA-RNA hybrids SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID (5'->5')-INTERNUCLEOTIDIC PHOSPHODIESTER LINKAGES; OLIGONUCLEOTIDES; CONFORMATION; NUCLEOSIDES AB On the basis of modeling studies, the (2-deoxy-alpha- and beta-D-erythro-pentofuranosyl) (thymin-1-yl) alkanes 1a,b and 2a,b were selected as potential conformational probes for altDNA oligonucleotides. A straightforward approach to the synthesis of 1a,b and 2a,b from commercial 2-deoxy-D-ribose (3) and 1-O-methyl-2-deoxy-3,5-di-O-p-toluoyl-D-erythro-pentofuranose (13), respectively, was developed. These nucleoside analogues were converted to the phosphoramidite derivatives 27a,b-30a,b and incorporated into oligonucleotide 31 at predetermined sites and defined internucleotidic motifs. The insertion of 1a,b according to either a (3' --> 5')- or a (3' --> 3')-internucleotidic polarity produced oligonucleotides exhibiting a slightly higher affinity for their complementary unmodified DNA sequence than for the corresponding RNA sequence (Table 3). Conversely, the incorporation of 2a into 31 according to a (3' --> 3')-orientation generated, for the first time, an altDNA oligonucleotide displaying a greater affinity for its complementary unmodified RNA sequence (Delta T-m = 6 degrees C) than for the corresponding DNA sequence (Delta T-m = 10 degrees C). thermodynamically less stable than the duplex having unmodified alpha-2'-deoxythymidine similarly incorporated into 31 (Delta Delta T-m = 3 degrees C). C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NATL CANC INST,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21701. NR 33 TC 22 Z9 22 U1 0 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 NOV 29 PY 1996 VL 61 IS 24 BP 8617 EP 8626 DI 10.1021/jo961548k PG 10 WC Chemistry, Organic SC Chemistry GA VV609 UT WOS:A1996VV60900046 ER PT J AU Ge, P Kirk, KL AF Ge, P Kirk, KL TI Synthesis of 2-deoxy-L-ascorbic acid SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 8 TC 16 Z9 16 U1 0 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 NOV 29 PY 1996 VL 61 IS 24 BP 8671 EP 8673 DI 10.1021/jo961247a PG 3 WC Chemistry, Organic SC Chemistry GA VV609 UT WOS:A1996VV60900058 ER PT J AU Tanaka, H Liang, CT AF Tanaka, H Liang, CT TI Mitogenic activity but not phenotype expression of rat osteoprogenitor cells in response to IGF-I is impaired in aged rats SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; DNA synthesis; gene expression; IGF-I; IGF-I receptor; osteoprogenitor cells ID GROWTH-FACTOR-I; BONE; RECEPTOR; PROLIFERATION; INVITRO; MARROW; GENE; BETA AB The age-related deficit in the doss response of osteoprogenitor cells to IGF-I was further investigated. As expected, the effective dose, but not the maximal effect, was shifted two orders of magnitude higher in old cells. In this paper, we examined whether this age-deficit can be attributed to an alteration in the expression and binding kinetics of IGF-I receptor. We showed that the levels of IGF-I receptor mRNA in cells, estimated by RT-PCR, were not significantly altered with age. Scatchard analysis showed that there were no significant differences in K-d and B-max in cells from the two age groups. In parallel study, we also showed that the expression of osteoblast phenotype markers was stimulated by IGF-I. However, no apparent differences in dose groups. These results suggest that defect(s) in cell proliferation in aging may occur specifically in the signal transduction pathway between the receptor and the mitogenic response but not in the pathway associated with phenotype expression. Copyright (C) 1996 Elsevier Science Ireland Ltd. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 26 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD NOV 29 PY 1996 VL 92 IS 1 BP 1 EP 10 DI 10.1016/S0047-6374(96)01793-9 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA WF416 UT WOS:A1996WF41600001 PM 9032750 ER PT J AU Wenkert, D Schoneberg, T Merendino, JJ Pena, MSR Vinitsky, R Goldsmith, PK Wess, J Spiegel, AM AF Wenkert, D Schoneberg, T Merendino, JJ Pena, MSR Vinitsky, R Goldsmith, PK Wess, J Spiegel, AM TI Functional characterization of five V2 vasopressin receptor gene mutations SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE vasopressin; receptor; mutations; nephrogenic diabetes insipidus; transfection; expression ID NEPHROGENIC DIABETES-INSIPIDUS; ADENYLYL-CYCLASE; MOLECULAR-CLONING; HORMONE RECEPTOR; TYPE-2 RECEPTOR; LIGAND-BINDING; EXPRESSION; RHODOPSIN AB COS7 cells were transiently transfected with plasmids encoding mutant forms of the V2 vasopressin receptors corresponding to mutations [Y280C, L292P, R337stop, V277A, and G12E (the latter found in the same kindred with L292P)] recently identified in subjects with X-linked nephrogenic diabetes insipidus (NDI). `cAMP response to dDAVP and AVP, saturation binding experiments with [H-3]-AVP, immunofluorescence; and indirect ELISA studies were performed to characterize the functional consequences of these mutations. The Y280C, L292P, and R337stop mutant V2 receptors show substantially decreased cell surface expression and are functionally inactive. The V277A mutant receptor, though well expressed at the cell surface as seen by immunofluorescence and ELISA and having a dissociation constant with AVP similar to the wild type receptor, was functionally less active as seen by a substantially decreased receptor number (B-max) and reduced cAMP stimulation by dDAVP. The G12E mutant was functionally the same as the wild type V2 receptor in both cAMP stimulation and binding. These results provide insight into residues critical for V2 receptor expression and function and also provide direct evidence that Y280C, L292P, R337stop and V277A mutations are the cause of X-linked NDI in affected subjects. Copyright (C) 1996 Elsevier Science Ireland Ltd. C1 NIDDKD, BIOORGAN CHEM LAB, NIH, BETHESDA, MD 20892 USA. RP NIDDKD, METAB DIS BRANCH, NIH, BLDG 10, ROOM 8C101, BETHESDA, MD 20892 USA. NR 24 TC 49 Z9 50 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 29 PY 1996 VL 124 IS 1-2 BP 43 EP 50 DI 10.1016/S0303-7207(96)03926-3 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA WC526 UT WOS:A1996WC52600006 PM 9027323 ER PT J AU Goldman, D AF Goldman, D TI Human genetics - High anxiety SO SCIENCE LA English DT Editorial Material ID CHROMOSOME-18 RP Goldman, D (reprint author), NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 14 TC 20 Z9 21 U1 23 U2 24 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 29 PY 1996 VL 274 IS 5292 BP 1483 EP 1483 DI 10.1126/science.274.5292.1483 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV775 UT WOS:A1996VV77500033 PM 8966620 ER PT J AU Lesch, KP Bengel, D Heils, A Sabol, SZ Greenberg, BD Petri, S Benjamin, J Muller, CR Hamer, DH Murphy, DL AF Lesch, KP Bengel, D Heils, A Sabol, SZ Greenberg, BD Petri, S Benjamin, J Muller, CR Hamer, DH Murphy, DL TI Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region SO SCIENCE LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; UNIFIED BIOSOCIAL THEORY; H-3 PAROXETINE BINDING; MYOCARDIAL-INFARCTION; QUANTITATIVE TRAITS; PERSONALITY-DISORDERS; SEXUAL ORIENTATION; MAJOR DEPRESSION; MARKERS; LINKAGE AB Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships. C1 NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. UNIV WURZBURG,INST HUMAN GENET,D-97074 WURZBURG,GERMANY. RP Lesch, KP (reprint author), UNIV WURZBURG,DEPT PSYCHIAT,FUCHSLEINSTR 15,D-97080 WURZBURG,GERMANY. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 73 TC 3319 Z9 3429 U1 31 U2 272 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 29 PY 1996 VL 274 IS 5292 BP 1527 EP 1531 DI 10.1126/science.274.5292.1527 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV775 UT WOS:A1996VV77500048 PM 8929413 ER PT J AU Cisneros, B Court, D Sanchez, A Montanez, C AF Cisneros, B Court, D Sanchez, A Montanez, C TI Point mutations in a transcription terminator, lambda tI, that affect both transcription termination and RNA stability SO GENE LA English DT Article DE terminator tI; transcription termination; mRNA secondary structure; mRNA decay ID INT GENE-EXPRESSION; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; SECONDARY STRUCTURE; MESSENGER-RNA; PHAGE-LAMBDA; SITE; ATTENUATOR; SEQUENCE; PROTEIN AB The terminator tI is located approx. 280 nucleotides beyond the int gene of bacteriophage h. Besides its role as a transcription terminator, tI may confer stability to the int message by protecting it from 3' exonucleolytic degradation. In order to study the role of the tI sequence in transcription termination and RNA stability, three different point mutations tI1, tI2, and tI3 were isolated and characterized. All the tl mutations map in the G+C-rich region of dyad symmetry in the terminator and decrease the transcriptional termination of tI in vivo from 99% for the wild type terminator to 81-93% as determined by galactokinase activity and in vitro from 80% for the wild type terminator to 8-12% using the E. coli RNA polymerase. Additionally, the tI mutations cause upstream transcript instability in vivo. This instability defect caused by tI mutations is compensated by the host mutant deficient in polynucleotide phosphorylase resulting in increased steady state levels of these mutant transcripts. The results show that the intact hairpin of tl is essential for efficient transcription termination and for maintaining mRNA stability by blocking the 3' to 5' exonucleolytic activity of polynucleotide phosphorylase. C1 INST POLITECN NACL,CTR INVEST & ESTUDIOS AVANZADOS,DEPT MOL BIOL & GENET,MEXICO CITY 07000,DF,MEXICO. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL CONTROL & GENET SECT,FREDERICK,MD 21702. NR 29 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 28 PY 1996 VL 181 IS 1-2 BP 127 EP 133 DI 10.1016/S0378-1119(96)00492-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VY055 UT WOS:A1996VY05500021 PM 8973320 ER PT J AU Medvedev, A Yan, ZH Hirose, T Giguere, V Jetten, AM AF Medvedev, A Yan, ZH Hirose, T Giguere, V Jetten, AM TI Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and characterization of its response element SO GENE LA English DT Article DE RZR/ROR; nuclear orphan receptor; response element; transactivation; gene expression; retinoid receptor ID STEROID-HORMONE RECEPTORS; NUCLEAR RECEPTOR; SUPERFAMILY; MEMBER; BINDING; FAMILY; IDENTIFICATION; MELATONIN; SUBFAMILY; MONOMERS AB In this study, we describe the cloning of the mouse homologue of the orphan receptor, RZR/ROR gamma, a member of the nuclear receptor superfamily, from a mouse muscle cDNA library. The amino acid sequence of mouse ROR gamma (mROR gamma) is highly homologous to that of human ROR gamma, with an overall identity of 88%. Northern blot analysis using RNA from different tissues showed that mROR gamma was found to be highly expressed in skeletal muscle, liver and kidney. Analysis of the ROR gamma-response element using in vitro synthesized ROR gamma revealed that it binds as a monomer to response elements composed of a single core motif GGTCA preceded by a 6 bp AT-rich sequence. The ROR gamma-binding specificity was further defined by mutational analysis of the consensus RORE. ROR gamma was able to activate RORE-dependent transcription of the CAT reporter gene in mouse fibroblast D1 cells. ROR alpha 1 and ROR gamma inhibit the transactivation induced by GAL4(DBD)-ROR gamma in fibroblast D1 cells suggesting that these receptors compete for binding to the same coactivators. C1 NIH,NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. OSAKA UNIV,SCH MED,DEPT MED 3,SUITA,OSAKA 565,JAPAN. MCGILL UNIV,MOL ONCOL GRP,ROYAL VICTORIA HOSP,DEPT BIOCHEM,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,MOL ONCOL GRP,ROYAL VICTORIA HOSP,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,MOL ONCOL GRP,ROYAL VICTORIA HOSP,DEPT ONCOL,MONTREAL,PQ H3A 1A1,CANADA. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 26 TC 78 Z9 80 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 28 PY 1996 VL 181 IS 1-2 BP 199 EP 206 DI 10.1016/S0378-1119(96)00504-5 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VY055 UT WOS:A1996VY05500032 PM 8973331 ER PT J AU Nelson, RG Bennett, PH Beck, GJ Tan, M Knowler, WC Mitch, WE Hirschman, GH Myers, BD AF Nelson, RG Bennett, PH Beck, GJ Tan, M Knowler, WC Mitch, WE Hirschman, GH Myers, BD TI Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OVERT NEPHROPATHY; ALBUMIN EXCRETION; NEPHROTIC HUMANS; PROTEINURIA; SELECTIVITY; PREVALENCE; DIET AB Background Non-insulin-dependent diabetes mellitus (NIDDM) is a major cause of end-stage renal disease. However, the course and determinants of renal failure in this type of diabetes have not been clearly defined. Methods We studied glomerular function at intervals of 6 to 12 months for 4 years in 194 Pima Indians selected to represent different stages in the development and progression of diabetic renal disease. Initially, 31 subjects had normal glucose tolerance, 29 had impaired glucose tolerance, 30 had newly diagnosed diabetes, and 104 had had diabetes for five years or more; of these 104, 20 had normal albumin excretion, 50 had microalbuminuria, and 34 had macroalbuminuria. The glomerular filtration rate, renal plasma flow, urinary albumin excretion, and blood pressure were measured at each examination. Results Initially, the mean (+/-SE) glomerular filtration rate was 143+/-7 ml per minute in subjects with newly diagnosed diabetes, 155+/-7 ml per minute in those with microalbuminuria, and 124+/-7 ml per minute in those with macroalbuminuria; these values were 16 percent, 26 percent, and 1 percent higher, respectively, than in the subjects with normal glucose tolerance (123+/-4 ml per minute). During four years of follow-up, the glomerular filtration rate increased by 18 percent in the subjects who initially had newly diagnosed diabetes (P=0.008); the rate declined by 3 percent in those with microalbuminuria at base line (P=0.29) and by 35 percent in those with macroalbuminuria (P<0.001). Higher base-line blood pressure predicted increasing urinary albumin excretion (P=0.006), and higher base-line urinary albumin excretion predicted a decline in the glomerular filtration rate (P<0.001). The initial glomerular filtration rate did not predict worsening albuminuria. Conclusions The glomerular filtration rate is elevated at the onset of NIDDM and remains so while normal albumin excretion or microalbuminuria persists. it declines progressively after the development of macroalbuminuria. (C)1996, Massachusetts Medical Society. C1 CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,DIABET RENAL DIS STUDY DATA COORDINATING CTR,CLEVELAND,OH 44195. EMORY UNIV,SCH MED,DIV RENAL,ATLANTA,GA 30322. NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,CHRON RENAL DIS PROGRAM,BETHESDA,MD. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. STANFORD UNIV,SCH MED,DIV NEPHROL,STANFORD,CA 94305. RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [N01-DK-6-2285, N01-DK-7-2291] NR 25 TC 289 Z9 297 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 NOV 28 PY 1996 VL 335 IS 22 BP 1636 EP 1642 DI 10.1056/NEJM199611283352203 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VV936 UT WOS:A1996VV93600003 PM 8929360 ER PT J AU Wang, Z Lee, KB Reed, E Sinha, BK AF Wang, Z Lee, KB Reed, E Sinha, BK TI Sensitization by interleukin-1 alpha of carboplatinum anti-tumor activity against human ovarian (NIH:OVCAR-3) carcinoma cells in vitro and in vivo SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-MELANOMA CELLS; LINE NIH-OVCAR-3; NECROSIS-FACTOR; CISPLATIN; POTENTIATION; COMBINATION; DOXORUBICIN; RESISTANCE; CYTOKINES; REPAIR AB Cytokines are directly cytotoxic to tumor cells in vitro and in vivo, and interleukin-1 alpha (IL-1 alpha) potentiates the cytotoxicity of a number of clinically active drugs in several human tumor cells, including carcinomas of the breast and ovary. In this study, we found that IL-1 alpha potentiated the cytotoxicity of carboplatin in human ovarian NIH:OVCAR-3 cancer cells during simultaneous drug exposure in vitro. Human ovarian carcinoma NIH:OVCAR-3 cells are resistant to clinically relevant concentrations of chemotherapeutic agents, including cisplatin. Both carboplatin and IL-1 alpha as single agents inhibited the growth of NIH:OVCAR-3 cells grown as xenograft in nude mice; however, carboplatin was more effective in delaying tumor growth, and this inhibition was dose-dependent. Treatment with IL-1 alpha followed by carboplatin caused a significant delay in tumor growth, resulting in a significant enhancement (4-fold) of the anti-tumor effect of carboplatin. In vitro potentiation of carboplatin cytotoxicity by IL-1 alpha did not involve formation of nitric oxide as IL-1 or combinations of IL-1 with carboplatin failed to modulate basal nitric oxide production in OVCAR-3 cells. Potentiation of the anti-tumor activity of carboplatin by IL-1 alpha was due to a significant (3- to 4-fold) increase in the accumulation of total Pt in IL-1-treated tumor xenograft, resulting in a 2-fold increase in DNA-Pt adduct formation in these tumors. In contrast, IL-1 alpha had no significant effect on DNA-Pt adduct formation in the kidney. The potent synergy of IL-1 alpha or and carboplatin in vitro and in vivo against ovarian carcinoma cells suggests that combinations of carboplatinum and interleukin-1 alpha may be effective against this disease in the clinic. (C) 1996 Wiley-Liss, Inc. C1 NCI,NIH,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 22 TC 5 Z9 5 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 NOV 27 PY 1996 VL 68 IS 5 BP 583 EP 587 DI 10.1002/(SICI)1097-0215(19961127)68:5<583::AID-IJC5>3.0.CO;2-V PG 5 WC Oncology SC Oncology GA VW532 UT WOS:A1996VW53200005 PM 8938138 ER PT J AU Kalebic, T Tsokos, M Helman, LJ AF Kalebic, T Tsokos, M Helman, LJ TI Suppression of rhabdomyosarcoma growth by fumagillin analog TNP-470 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ANGIOGENESIS INHIBITOR TNP-470; ENDOTHELIAL-CELLS; TUMOR-GROWTH; METASTASIS; AGM-1470; EXPRESSION; AGENTS AB The purpose of our study was to investigate a novel therapeutic approach for rhabdomyosarcoma (RMS) in an animal model. The pursuit of new therapeutic modalities for RMS is critically important since this type of tumor is the most common soft tissue sarcoma in children and because patients with metastatic disease may not be cured with current therapeutic modalities. We studied whether RMS growth may be suppressed by TNP-470, an analog of fumagillin, which was found to inhibit neoangiogenesis. Our data had shown that animals treated with TNP-470 (60 mg/kg), over a specific period of time, had approximately 50% smaller tumors than controls. Consistent with previous observations, treatment with TNP-470 decreases the level of the cyclin DI. Tumors dissected from TNP-470-treated animals had also considerable necrotic areas. In addition, TNP-470 had a direct cytotoxic effect on RMS cells in vitro. Our study has shown, therefore, that RMS in an animal model and in vitro responds to treatment with TNP-470, which suggests that the inhibitors of angiogenesis may be useful in a novel therapeutic design for RMS. (C) 1996 Wiley-Liss, Inc. C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. RP Kalebic, T (reprint author), NCI,PEDIAT BRANCH,MOL ONCOL SECT,BLDG 10-13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 27 PY 1996 VL 68 IS 5 BP 596 EP 599 PG 4 WC Oncology SC Oncology GA VW532 UT WOS:A1996VW53200007 PM 8938140 ER PT J AU Gemma, A Takenoshita, S Hagiwara, K Okamoto, A Spillare, EA McMemamin, MG Hussain, SP Forrester, K Zariwala, M Xiong, Y Harris, CC AF Gemma, A Takenoshita, S Hagiwara, K Okamoto, A Spillare, EA McMemamin, MG Hussain, SP Forrester, K Zariwala, M Xiong, Y Harris, CC TI Molecular analysis of the cyclin-dependent kinase inhibitor genes p15(INK4b/MTS2), p16(INK4/MTS1), p18 and p19 in human cancer cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LUNG-CANCER; MUTATIONS; SUPPRESSION; GROWTH; FAMILY; CDK6 AB Cyclin-dependent kinase-4 inhibitor genes (INK4) regulate the cell cycle and are candidate tumor-suppressor genes. To determine if alterations in the coding regions of the p18 and p19 genes, which are novel members of the INK4 family and if they correlate with the development of human cancer, 100 human cancer cell lines were analyzed. two other INK4 gene family members, p15(INK4b/MTS2) Md p16(INK4/MTS1) genes were also analyzed. Homozygous deletions of the p15(INK4b/MTS2) gene were detected in 29 cancer cell lines. Thirty-five homozygous deletions and 7 intragenic mutations of the p16(INK4/MTS1) gene were also detected in these cell lines. Neither homozygous deletions nor intragenic mutations of the p18 and p19 genes were found except in an ovarian cancer cell line, SKOV3, harboring a single base pair deletion in exon 1 of p19. In p16(INK4/MTS1) expression analysis. 5 cell lines with both authentic and alternative spliced 5 p16(INK4)/MTS1 mRNA had no detectable p16(INK4/MTS1) protein. These results suggest the hypotheses that either post-translational modification or enhanced degradation may be responsible for the lack of detection of the p16(INK4/MTS1) protein. Using Western blot analysis, subsets of 26 human cancer cell lines were examined for pig expression and 39 cell lines for p19 expression. All of these cell lines expressed the pig or p19 protein, with the exception of SKOV3, which did not express p19, Therefore, the INK4 gene family may be divided into 2 groups. One group includes p15(INK4b/MTS2) and p16(INK4/MTS1), in which genetic and epigenetic alterations might contribute to the development of human cancers. The other group includes p18 and p19, in which somatic mutations are uncommon in many types of human cancer, and their role in human carcinogenesis and cancer progression is uncertain. (C) 1996 Wiley-Liss, Inc. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,DIV BASIC SCI,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. NR 22 TC 48 Z9 48 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 NOV 27 PY 1996 VL 68 IS 5 BP 605 EP 611 DI 10.1002/(SICI)1097-0215(19961127)68:5<605::AID-IJC9>3.0.CO;2-2 PG 7 WC Oncology SC Oncology GA VW532 UT WOS:A1996VW53200009 PM 8938142 ER PT J AU Tyson, JE Younes, N Verter, J Wright, LL AF Tyson, JE Younes, N Verter, J Wright, LL TI Viability, morbidity, and resource use among newborns of 501- to 800-g birth weight SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DIAGNOSIS-RELATED GROUPS; NEONATAL INTENSIVE-CARE; EXTREMELY PREMATURE; GESTATIONAL-AGE; INFANTS BORN; MORTALITY; OUTCOMES; SEVERITY; CHILDREN; NETWORK AB Objectives.-To assess risk factors affecting viability and analyze the effects of mechanical ventilation (MV) on neonatal outcome and resource use among extremely premature infants. Design.-Inception cohort study. Setting.-Neonatal intensive care units of the 12-center National Institute of Child Health and Human Development Neonatal Research Network. Participants.-A total of 1126 infants with a birth weight of 501 to 800 g born in network centers between January 1, 1994, and December 31, 1995. Main Outcome Measures.-Observed survival; maximum estimated survival (assuming the same survival among infants who died without MV as among infants in the same risk category who received MV); observed and maximum estimated survival without severe brain injury (either interventricular echodensity with ventricular dilation or parenchymal echodensity); hospital stay; resource investment. Results.-Overall mortality was 43%; mortality in infants without MV was 93%, A total of 15% of ail the infants died without MV. Females, small-for-gestational-age infants, and infants whose mothers received antenatal steroids had an advantage in survival with MV equivalent to an increase in birth weight of 90 g, 57 g, and 67 g, respectively, The corresponding advantage of these infants in survival without severe brain injury was 107 g, 97 g, and 64 g, respectively, Females in the lowest birth-weight group were more likely to die without MV than were larger males with a similar estimated likelihood of survival with MV. Mean hospital stay was 115 days for the survivors, values much greater than the 17.9-day standard for 501- to 800-g survivors under the diagnosis related group system. Resource investment was considerable (127 hospital days per survivor and 148 days per survivor without severe brain injury), but, like outcome, varied markedly between risk categories. Had MV been used for all infants who died, we estimate a substantial increase in resource use and a maximum of 8 additional survivors (no more than 6 without severe brain injury per 100 infants with a birth weight of 501 to 800 g. Conclusions.-Although recommendations to initiate or forgo MV for extremely premature infants have often focused on 1 factor(birth weight or gestational age), multiple factors should be considered. Other factors being equal, our analyses support use of MV for females at a minimum birth weight approximately 100 g lower than that for males. The current diagnosis related group reimbursement system can be expected to compromise resources for 501- to 800-g infants who would benefit from MV. Such care entails considerable resource use, although the cost per life-year gained is likely to be considerably less than that for many adults given intensive care. Our findings can be used to facilitate more appropriate treatment decisions, determine adequate resources, and better inform the debate about the benefits and burdens of intensive care for extremely premature newborns. C1 GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC. NICHHD,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV CINCINNATI,CINCINNATI,OH. EMORY UNIV,ATLANTA,GA 30322. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. STANFORD UNIV,STANFORD,CA 94305. WAYNE STATE UNIV,DETROIT,MI. BROWN UNIV,WOMEN & INFANTS HOSP,PROVIDENCE,RI. YALE UNIV,NEW HAVEN,CT. RP Tyson, JE (reprint author), UNIV TEXAS,SW MED CTR,DEPT PEDIAT,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. FU NICHD NIH HHS [1U10 HD 21373, 2U01 HD 19897] NR 58 TC 103 Z9 104 U1 0 U2 3 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 NOV 27 PY 1996 VL 276 IS 20 BP 1645 EP 1651 DI 10.1001/jama.276.20.1645 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VU209 UT WOS:A1996VU20900031 PM 8922450 ER PT J AU Noland, TA Raynor, RL Jideama, NM Guo, XD Kazanietz, MG Blumberg, PM Solaro, RJ Kuo, JF AF Noland, TA Raynor, RL Jideama, NM Guo, XD Kazanietz, MG Blumberg, PM Solaro, RJ Kuo, JF TI Differential regulation of cardiac actomyosin S-1 MgATPase by protein kinase C isozyme-specific phosphorylation of specific sites in cardiac troponin I and its phosphorylation site mutants SO BIOCHEMISTRY LA English DT Article ID ADULT-RAT CARDIOMYOCYTES; MYOSIN LIGHT CHAIN-2; PHORBOL ESTER; CA2+-STIMULATED MGATPASE; RECONSTITUTED ACTOMYOSIN; INHIBITORY SUBUNIT; MYOCARDIAL-CELLS; MYOCYTES; HEART; CONTRACTION AB The significance of site-specific phosphorylation by protein kinase C (PKC) isozymes alpha and delta and protein kinase A (PKA) of troponin I (TnI) and its phosphorylation site mutants in the regulation of Ca2+-stimulated MgATPase activity of reconstituted actomyosin S-1 was investigated. The genetically defined TnI mutants used were T144A, S43A/S45A, S43A/S45A/T144A (in which the PKC phosphorylation sites Thr-144 and Ser-43/Ser-45 were respectively substituted by Ala) and N32 (in which the first 32 amino acids in the NH2-terminal sequence containing Ser-23/Ser-24 were deleted). Although the PKC isozymes displayed different substrate phosphorylation kinetics, PKC-alpha phosphorylated equally well TnI wild type and all mutants, whereas N32 was a much poorer substrate for PKC-delta. Furthermore, the two PKC isozymes exhibited discrete specificities in phosphorylating distinct sites in TnI and its mutants, either as individual subunits or as components of the reconstituted troponin complex. Unlike PKC-alpha, PKC-delta favorably phosphorylated the PKA-preferred site Ser-23/Ser-24 and hence, like PKA, reduced the Ca2+ sensitivity of the reconstituted actomyosin S-1 MgATPase. In contrast, PKC-alpha preferred to phosphorylate Ser-43/Ser-45 (common sites for all isozymes) and thus reduced the maximal Ca2+-stimulated activity of the MgATPase. In this respect, PKC-delta, by cross-phosphorylating the PKA sites, functioned as a hybrid of PKC-alpha and PKA. The site specificities and hence functional differences between PKC-a and -delta were most evident at low phosphorylation (1 mol of phosphate/mol) of TnI wild type and were magnified when S43A/S45A and N32 were used as substrates. The present study has demonstrated, for the first time, that distinct functional consequences could arise from the site-selective preferences of PKC-alpha and -delta for phosphorylating a single substrate in the myocardium, i.e., TnI. C1 UNIV ILLINOIS,COLL MED,DEPT PHYSIOL & BIOPHYS,CHICAGO,IL 60612. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOL MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. RP Noland, TA (reprint author), EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322, USA. FU NHLBI NIH HHS [HL-15696, HL-22231, HL-49934] NR 53 TC 64 Z9 64 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 26 PY 1996 VL 35 IS 47 BP 14923 EP 14931 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV237 UT WOS:A1996VV23700032 PM 8942657 ER PT J AU Desimone, R AF Desimone, R TI Neural mechanisms for visual memory and their role in attention SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Memory - Recording Experience in Cells and Circuits CY FEB 17-20, 1996 CL NATL ACAD SCI IRVINE, IRVINE, CA HO NATL ACAD SCI IRVINE DE primate; inferior temporal cortex; neurophysiology; prefrontal cortex; visual search ID INFERIOR TEMPORAL CORTEX; SHORT-TERM-MEMORY; DORSOLATERAL PREFRONTAL CORTEX; SACCADE-RELATED ACTIVITY; DELAYED-RESPONSE PERFORMANCE; LATERAL INTRAPARIETAL AREA; NEURONAL-ACTIVITY; RECOGNITION MEMORY; RHESUS-MONKEYS; ORIENTATION DISCRIMINATION AB Recent studies show that neuronal mechanisms for learning and memory both dynamically modulate and permanently alter the representations of visual stimuli in the adult monkey cortex, Three commonly observed neuronal effects in memory-demanding tasks are repetition suppression, enhancement, and delay activity, In repetition suppression, repeated experience with the same visual stimulus leads to both short- and long-term suppression of neuronal responses in subpopulations of visual neurons, Enhancement works in an opposite fashion, in that neuronal responses are enhanced for objects with learned behavioral relevance, Delay activity is found in tasks in which animals are required to actively hold specific information ''on-line'' for short periods, Repetition suppression appears to he an intrinsic property of visual cortical areas such as inferior temporal cortex and is thought to be important for perceptual learning and priming, By contrast, enhancement and delay activity mag depend on feedback to temporal cortex from prefrontal cortex and are thought to be important for working memory, All of these mnemonic effects on neuronal responses bias the competitive interactions that take place between stimulus representations in the cortex when there is more than one stimulus in the visual field, As a result, memory will often determine the winner of these competitions and, thus, will determine which stimulus is attended. RP Desimone, R (reprint author), NIMH,NEUROPSYCHOL LAB,49 CONVENT DR,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 66 TC 651 Z9 663 U1 4 U2 37 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 NOV 26 PY 1996 VL 93 IS 24 BP 13494 EP 13499 DI 10.1073/pnas.93.24.13494 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700010 PM 8942962 ER PT J AU Zheng, RL Jenkins, TM Craigie, R AF Zheng, RL Jenkins, TM Craigie, R TI Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-BINDING DOMAIN; TYPE-1 INTEGRASE; RETROVIRAL INTEGRATION; ESCHERICHIA-COLI; PROTEIN; IDENTIFICATION; RESIDUES; INVITRO; REGION AB The N-terminal domain of HIV-1 integrase contains a pair of His and Cys residues (the HHCC motif) that are conserved among retroviral integrases. Although His and Cys residues are often involved in binding zinc, the HHCC motif does not correspond to any recognized class of zinc binding domain. We have investigated the binding of zinc to HIV-1 integrase protein and find that it binds zinc with a stoichiometry of one zinc per integrase monomer. Analysis of zinc binding to deletion derivatives of integrase locates the binding site to the N-terminal domain. Integrase with a mutation in the HHCC motif does not bind zinc, consistent with coordination of zinc by these residues. The isolated N-terminal domain is disordered in the absence of zinc but, in the presence of zinc, it adopts a secondary structure with a high alpha helical content. Integrase bound by zinc tetramerizes more readily than the apoenzyme and is also more active than the apoenzyme in in vitro integration assays. We conclude that binding of zinc to the HHCC moth stabilizes the folded state of the N-terminal domain of integrase and bound zinc is required for optimal enzymatic activity. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 42 TC 255 Z9 265 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 NOV 26 PY 1996 VL 93 IS 24 BP 13659 EP 13664 DI 10.1073/pnas.93.24.13659 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700038 PM 8942990 ER PT J AU Alcorta, DA Xiong, Y Phelps, D Hannon, G Beach, D Barrett, JC AF Alcorta, DA Xiong, Y Phelps, D Hannon, G Beach, D Barrett, JC TI Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; CELL-CYCLE; RETINOBLASTOMA-PROTEIN; GENE-PRODUCT; EXPRESSION; P53; P21; SUPPRESSION; CULTURE; ARREST AB Human diploid fibroblasts (HDFs) can be grown in culture for a finite number of population doublings before they cease proliferation and enter a growth-arrest state termed replicative senescence. The retinoblastoma gene product, Rb, expressed in these cells is hypophosphorylated. To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and Interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs, Cellular p21 protein expression increased dramatically during the final two to three passages when the majority of cells lost their growth potential and neared senescence but p21 levels declined in senescent HDFs, During this period, p16 mRNA and cellular protein levels gradually rose with the protein levels in senescent HDFs reaching nearly IO-fold higher than early passage cells. In senescent HDFs, p16 was shown to be complexed to both CDK4 and CDK6. Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 Is the major CDK inhibitor for both CDK4 and CDK6 kinases, Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors, Based upon these results, we propose that senescence is a multistep process requiring the expression of both p21 and p16, p16 up-regulation is a key event in the terminal stages of growth arrest In senescence, which may explain why p16 but not p21 is commonly mutated in immortal cells and human tumors. C1 UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. COLD SPRING HARBOR LAB,HOWARD HUGHES MED INST,COLD SPRING HARBOR,NY 11724. RP Alcorta, DA (reprint author), NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 609 Z9 642 U1 3 U2 27 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 NOV 26 PY 1996 VL 93 IS 24 BP 13742 EP 13747 DI 10.1073/pnas.93.24.13742 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700053 PM 8943005 ER PT J AU Sgadari, C Angiolillo, AL Cherney, BW Pike, SE Farber, JM Koniaris, LG Vanguri, P Burd, PR Sheikh, N Gupta, G TeruyaFeldstein, J Tosato, G AF Sgadari, C Angiolillo, AL Cherney, BW Pike, SE Farber, JM Koniaris, LG Vanguri, P Burd, PR Sheikh, N Gupta, G TeruyaFeldstein, J Tosato, G TI Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EPSTEIN-BARR-VIRUS; PLATELET FACTOR-IV; X-C CHEMOKINE; BURKITTS-LYMPHOMA; SOLID TUMORS; B-CELLS; IN-VIVO; ANGIOGENESIS; IP-10; INHIBITION AB Human Burkitt lymphoma cell lines give rise to progressively growing subcutaneous tumors in athymic mice. These tumors are induced to regress by inoculation of Epstein-Barr virus-immortalized normal human lymphocytes. In the present study, analysis of profiles of murine cytokine/chemokine gene expression in Burkitt tumor tissues excised from the nude mice showed that expression of the murine alpha-chemokine interferon-inducible protein-10 (IP-10) was higher in the regressing than in the progressive Burkitt tumors, We tested the effects of IP-10 on Burkitt tumor growth in nude mice. Inoculation of established Burkitt tumors either with crude preparations of murine IP-10 or with purified human IP-10 caused visible tumor necrosis in a proportion of the animals, although no complete tumor regressions were observed, Constitutive expression of murine IP-10 in Burkitt cells reduced their ability to grow as subcutaneous tumors, and caused visible tumor necrosis in a proportion of the animals, Histologically, IP-10-treated and IP-10-expressing Burkitt tumors had widespread evidence of tumor tissue necrosis and of capillary damage, including intimal thickening and vascular thrombosis. Thus, IP-10 is an antitumor agent that promotes damage in established tumor vasculature and causes tissue necrosis in human Burkitt lymphomas established subcutaneously in athymic mice. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20010. NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 33 TC 186 Z9 194 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 NOV 26 PY 1996 VL 93 IS 24 BP 13791 EP 13796 DI 10.1073/pnas.93.24.13791 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700062 PM 8943014 ER PT J AU Nelson, TJ Cavallaro, S Yi, CL McPhie, D Schreurs, BG Gusev, PA Favit, A Zohar, O Kim, J Beushausen, S Ascoli, G Olds, J Neve, R Alkon, DL AF Nelson, TJ Cavallaro, S Yi, CL McPhie, D Schreurs, BG Gusev, PA Favit, A Zohar, O Kim, J Beushausen, S Ascoli, G Olds, J Neve, R Alkon, DL TI Calexcitin: A signaling protein that binds calcium and GTP, inhibits potassium channels, and enhances membrane excitability SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; GLUTATHIONE-S-TRANSFERASE; MEMORY STORAGE; KINASE-C; ESCHERICHIA-COLI; MOLECULAR-CHANGES; PHOSPHORYLATION; CELLS; SPECIFICITY; ACTIVATION AB A previously uncharacterized 22-kDa Ca2+-binding protein that also binds guanosine nucleotides was characterized, cloned, and analyzed by electrophysiological techniques, The cloned protein, calexcitin, contains two EF-hands and also has homology with GTP-binding proteins in the ADP ribosylation factor family. In addition to binding two molecules of Ca2+, calexcitin bound GTP and possessed GTPase activity, Calexcitin is also a high affinity substrate for protein kinase C. Application of calexcitin to the inner surface of inside-out patches of human fibroblast membranes, in the presence of Ca2+ and the absence of endogenous Ca2+/calmodulin kinase type II or protein kinase C activity, reduced the mean open time and mean open probability of 115 +/- 6 pS K+ channels, Calexcitin thus appears to directly regulate K+ channels, When microinjected into molluscan neurons or rabbit cerebellar Purkinje cell dendrites, calexcitin was highly effective in enhancing membrane excitability. Because calexcitin translocates to the cell membrane after phosphorylation, calexcitin could serve as a Ca2+-activated signaling molecule that increases cellular excitability, which would in turn increase Ca2+ influx: through the membrane, This is also the first known instance of a GTP-binding protein that binds Ca2+. C1 NINCDS, NEUROCHEM LAB, NIH, BETHESDA, MD 20892 USA. HARVARD UNIV, SCH MED, MCLEAN HOSP, BELMONT, MA 02178 USA. KOREA ADV INST SCI & TECHNOL, KOREA RES INST BIOSCI & BIOTECHNOL, PROT ENGN GRP, TAEJON 305600, SOUTH KOREA. GEORGE MASON UNIV, FAIRFAX, VA 22030 USA. RP NINCDS, LAB ADAPT SYST, NIH, BLDG 36, RM 4D04, BETHESDA, MD 20892 USA. RI Cavallaro, Sebastiano/F-3104-2010; OI Cavallaro, Sebastiano/0000-0001-7590-1792; Schreurs, Bernard/0000-0002-5776-0807 NR 56 TC 45 Z9 45 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 1996 VL 93 IS 24 BP 13808 EP 13813 DI 10.1073/pnas.93.24.13808 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700065 PM 8943017 ER PT J AU Larionov, V Kouprina, N Graves, J Resnick, MA AF Larionov, V Kouprina, N Graves, J Resnick, MA TI Highly selective isolation of human DNAs from rodent-human hybrid cells as circular yeast artificial chromosomes by transformation-associated recombination cloning SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE selective cloning; human chromosomes ID SACCHAROMYCES-CEREVISIAE; EFFICIENT MANIPULATION; SYSTEM; CLONES; YACS; CONSTRUCTION; MAINTENANCE; FREQUENCY; SEGMENTS; VECTORS AB Transformation-associated recombination (TAR) can be exploited in yeast to clone human DNAs. TAR cloning was previously accomplished using one or two telomere-containing vectors with a common human repeat(s) that could recombine with human DNA during transformation to generate yeast artificial chromosomes (YACs). On basis of the proposal that broken DNA ends are more recombinogenic than internal sequences, we have investigated if TAR cloning could be applied to the generation of circular YACs by using a single centromere vector containing various human repeats at opposite ends. Transformation with these vectors along with human DNA led to the efficient isolation of circular YACs with a mean size of approximate to 150 kb. The circular YACs are stable and they can be easily separated from yeast chromosomes or moved into bacterial cells if the TAR vector contains an Escherichia coli F-factor cassette. More importantly, circular TAR cloning enabled the selective isolation of human DNAs from monochromosomal human-rodent hybrid cell lines. Although <2% of the DNA in the hybrid cells was human, as much as 80% of transformants had human DNA YACs when a TAR cloning vector contained Alu repeats, The level of enrichment of human DNA was nearly 3000-fold, A comparable level of enrichment was demonstrated with DNA isolated from a radiation hybrid cell line containing only 5 Mb of human DNA, A high selectivity of human DNA cloning was also observed for linear TAR cloning with two telomere vectors. No human-rodent chimeras were detected among YACs generated by TAR cloning. The results with a circular TAR cloning vector or two vectors differed from results with a single-telomere vector in that the Latter often resulted in a series of terminal deletions in linear YACs, This could provide a means for physical mapping of cloned material. RP Larionov, V (reprint author), NIEHS,LAB MOL SCI,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 23 TC 33 Z9 34 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 1996 VL 93 IS 24 BP 13925 EP 13930 DI 10.1073/pnas.93.24.13925 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700085 PM 8943037 ER PT J AU Bergsagel, PL Chesi, M Nardini, E Brents, LA Kirby, SL Kuehl, WM AF Bergsagel, PL Chesi, M Nardini, E Brents, LA Kirby, SL Kuehl, WM TI Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromosome translocation; isotype switch recombination; cyclin D1; immunoglobulin heavy chain gene ID PLASMA-CELL LEUKEMIA; HOMOLOGOUS RECOMBINATION; B-CELLS; ESTABLISHMENT; LINES; GENE; INTERLEUKIN-6; PATIENT; SUBLOCALIZATION; REARRANGEMENTS AB In multiple myeloma, karyotypic. 14q32 translocations have been identified at a variable frequency (10-60% in different studies). In the majority of cases, the partner chromosome has not been identified (14q+), and in the remaining cases, a diverse array of chromosomal partners has been implicated, with 11q13 being the most common. We developed a comprehensive Southern blot assay to identify and distinguish different kinds of immunoglobulin heavy chain (IgH) switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only one switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma sell lines, including seven of eight karyotyped lines that have no detectable 14q32 translocation. From all nine lines or tumor samples analyzed Further, cloned illegitimate switch recombination fragments were confirmed to be IgH switch translocation breakpoints. In three of these cases, the translocation breakpoint was shown to be present in the primary tumor. These translocation breakpoints involve six chromosomal loci: 4p16.3 (two lines and the one tumor); 6; 8q24.13; 11q13.3 (in three lines); 16q23.1; and 21q22.1. We suggest that translocations into the IgH locus (i) are frequent (karyotypic 14q32 translocations and/or illegitimate switch recombination fragments are present in primary tumor samples and in 19 of 21 lines that we have analyzed); (ii) occur mainly in switch regions; and (iii) involve a diverse but nonrandom array (i.e., frequently 11q13 or 4p16) of chromosomal partners. This appears to be the most frequent genetic abnormality in multiple myeloma. C1 NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. RP Bergsagel, PL (reprint author), CORNELL UNIV,COLL MED,NEW YORK,NY 10021, USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 46 TC 261 Z9 265 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 1996 VL 93 IS 24 BP 13931 EP 13936 DI 10.1073/pnas.93.24.13931 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700086 PM 8943038 ER PT J AU VanLeeuwen, JEM Kearse, KP AF VanLeeuwen, JEM Kearse, KP TI Deglucosylation of N-linked glycans is an important step in the dissociation of calreticulin class I TAP complexes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOPLASMIC-RETICULUM; MOLECULAR CHAPERONE; INTRACELLULAR-TRANSPORT; T-CELLS; CALNEXIN; ASSOCIATION; PROTEINS; OLIGOSACCHARIDE; DEFICIENT; PEPTIDE AB Recent evidence indicates that newly synthesized major histocompatibility complex (MHC) class I proteins interact with calnexin, a transmembrane endoplasmic reticulum protein specific for certain glycoproteins bearing monoglucosylated glycans, Here, we studied the association of newly synthesized class I proteins with calreticulin, a soluble calnexin-related ER protein, in murine T cells, We found that, unlike calnexin-class I interactions, calreticulin assembly with class I proteins was markedly decreased in the absence of Pt microglobulin expression and that calreticulin associated with a subset of class I glycoforms distinct from those assembled with calnexin but similar to those bound to TAP (transporter associated with antigen processing) proteins. Finally, these studies show that deglucosylation of N-linked glycans is important for dissociation of class I proteins from both calreticulin and TAP and that the vast majority of newly synthesized class I proteins associated with calreticulin are simultaneously assembled with TAP. The data demonstrate that calnexin and calreticulin chaperones assemble with distinct MHC class I assembly intermediates in the ER and show that glycan processing is functionally coupled to release of R-IHC class I proteins from peptide transport molecules. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI van Leeuwen, Jeroen/G-3555-2010 NR 35 TC 75 Z9 75 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 1996 VL 93 IS 24 BP 13997 EP 14001 DI 10.1073/pnas.93.24.13997 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700097 PM 8943049 ER PT J AU Jonason, AS Kunala, S Price, GJ Restifo, RJ Spinelli, HM Persing, JA Leffell, DJ Tarone, RE Brash, DE AF Jonason, AS Kunala, S Price, GJ Restifo, RJ Spinelli, HM Persing, JA Leffell, DJ Tarone, RE Brash, DE TI Frequent clones of p53-mutated keratinocytes in normal human skin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sunlight; ultraviolet; carcinogenesis; tumor promotion; clonal expansion ID TUMOR-SUPPRESSOR GENE; P53 GENE; SOLAR KERATOSES; CELL CARCINOMA; CANCER; PROTEIN; UV; MUTATIONS; EXPOSURE; SUNLIGHT AB The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles, These clones, 60-3000 cells in size, are present at frequencies exceeding 10 cells per cm(2) and together involve as much as 4% of the epidermis. in sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin, We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells, These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to canter. C1 YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT SURG,SECT PLAST SURG,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,YALE COMPREHENS CANC CTR,NEW HAVEN,CT 06510. CONNECTICUT CTR PLAST SURG,NEW HAVEN,CT 06511. NCI,BIOSTAT BRANCH,NIH,BETHESDA,MD 20205. RP Jonason, AS (reprint author), YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,333 CEDAR ST,HRT 309,NEW HAVEN,CT 06510, USA. FU NCI NIH HHS [R01 CA055737, CA55737] NR 36 TC 410 Z9 414 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 NOV 26 PY 1996 VL 93 IS 24 BP 14025 EP 14029 DI 10.1073/pnas.93.24.14025 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700102 PM 8943054 ER PT J AU Kinter, AL Ostrowski, M Goletti, D Oliva, A Weissman, D Gantt, K Hardy, E Jackson, R Ehler, L Fauci, AS AF Kinter, AL Ostrowski, M Goletti, D Oliva, A Weissman, D Gantt, K Hardy, E Jackson, R Ehler, L Fauci, AS TI HIV replication in CD4(+) T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous beta-chemokines and the viral inductive effects of other endogenous cytokines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE proinflammatory; regulation ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; FACTOR-ALPHA; EXPRESSION; MACROPHAGES; INTERLEUKIN-6; MIP-1-ALPHA; RECEPTOR; INVITRO AB This study demonstrates that the beta-chemokines macrophage inflammatory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) and, RANTES (regulated on activation, normally T-cell expressed and secreted) inhibit human immunodeficiency virus (HIV) replication in anti-CD3 or recall antigen-stimulated peripheral blood mononuclear cells (PBMCs) of asymptomatic HIV-infected subjects, Significant levels of beta-chemokines were produced by both CD4(+) and CD8(+) PBMC subsets from HIV-infected individuals, Neutralization of endogenous MIP-1 alpha, MIP-1 beta, and RANTES did not rescue HIV replication in cultures to which greater than 10% CD8(+) T cells had been added, indicating that the HIV suppressor activity of CD8(+) T cells cannot be explained entirely by the beta-chemokines, However, significant enhancement of viral replication was observed upon neutralization of endogenous beta-chemokines in CD8-depleted or CD4(+) PBMCs from most donors, particularly in cultures with low inducible levels of HIV production, In contrast, certain endogenous proinflammatory cytokines induced HIV replication in these same cells, These data suggest that the levels of HIV replication in CD4(+) PBMC reflect the balance of the opposing effects of endogenous suppressive factors, such as the beta-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor cu and interleukin 1 beta. RP Kinter, AL (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A33,10 CTR DR,MSC-1576,BETHESDA,MD 20892, USA. NR 29 TC 99 Z9 102 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 NOV 26 PY 1996 VL 93 IS 24 BP 14076 EP 14081 DI 10.1073/pnas.93.24.14076 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VV467 UT WOS:A1996VV46700111 PM 8943063 ER PT J AU Moller, JR AF Moller, JR TI Rapid conversion of myelin-associated glycoprotein to a soluble derivative in primates SO BRAIN RESEARCH LA English DT Article DE myelin; myelin-associated glycoprotein; myelin basic protein; primate; protease ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; BASIC-PROTEIN BP; NEUTRAL PROTEASE; CEREBROSPINAL-FLUID; PURIFIED MYELIN; MONOCLONAL-ANTIBODIES; MOLECULAR-CLONING; CDNA CLONING; E-64 ANALOG AB Myelin-associated glycoprotein (MAG) is susceptible to proteolysis by a calcium-activated neutral protease which is located in myelin. The conversion of MAG (M(r) 100,000) to its soluble derivative dMAG (M(r) 90,000) occurs much more rapidly in myelin from human white matter than in myelin from rat brain, and the rate of formation of dMAG is increased even more in myelin from white matter of patients with multiple sclerosis (MS). The MAG to dMAG conversion was studied in several species, ranging from mice to non-human primates and humans to determine what animal model would be the most appropriate for investigating the MAG to dMAG reaction in demyelinating disorders. Myelin fractions from brains of these species were prepared and incubated at 37 degrees C in 0.2 M NH4HCO3, pH 7.4 for time periods ranging from 5 min to 24 h. Western blot analysis of the samples, taken at the end points of the different incubation periods, showed that the time required for a 50% conversion of MAG to dMAG was 18-24 h in myelin from rodents to bovine. The non-human primate studies revealed a 50% conversion at 2 h for marmoset samples and rhesus monkey samples, 20 min for gorilla samples and 10 min for chimpanzee samples. Human myelin samples needed only 5 min for a 50% conversion of MAG to dMAG. The reason for the significantly faster formation of dMAC in primate myelin is unknown and currently is being investigated. RP Moller, JR (reprint author), NINCDS,LMCN,DEMYELINATING DISORDERS UNIT,NIH,49 CONVENT DR,MSC 4440,BETHESDA,MD 20892, USA. NR 42 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 25 PY 1996 VL 741 IS 1-2 BP 27 EP 31 DI 10.1016/S0006-8993(96)00882-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VZ081 UT WOS:A1996VZ08100003 PM 9001700 ER PT J AU Winsky, L Isaacs, KR Jacobowitz, DM AF Winsky, L Isaacs, KR Jacobowitz, DM TI Calretinin mRNA and immunoreactivity in the medullary reticular formation of the rat: Colocalization with glutamate receptors SO BRAIN RESEARCH LA English DT Article DE calcium binding protein; calretinin; double immunohistochemical labeling; hybridization histochemistry, in situ; glutamate receptor; reticular formation ID CALCIUM-BINDING PROTEIN; BRAIN-STEM; NERVOUS-SYSTEM; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOCYTOCHEMICAL LOCALIZATION; SENSORY NEURONS; MESSENGER-RNAS; PARVALBUMIN; IDENTIFICATION; CALBINDIN-D(28K) AB Calretinin-positive cells were identified in the medullary reticular formation of the rat by both immunohistochemistry and in situ hybridization histochemistry. In addition, double immunocytochemical labeling was used to examine the degree of colocalization of calretinin with GluR(2)/R(3), GluR(4) and GluR(5-7) glutamate receptor subtypes. Results indicated regional variation in calretinin expression across reticular formation regions with the exception of the lamest cells which were mostly calretinin-positive. Calretinin mRNA was particularly abundant in the parvocellular reticular nucleus. Most calretinin-immunoreactive cells also expressed at least one of the glutamate receptor subtypes examined with the exception of the smallest calretinin-positive cells of the parvocellular reticular formation which were generally not immunoreactive for any of the glutamate receptors examined. Calretinin immunoreactivity was colocalized with immunoreactivity for all three glutamate receptor subtypes examined in most of the large cells of the reticular formation. Immunoreactivity for the GluR, antibody was least abundant in the reticular formation and GluR, immunoreactive cells were least likely to co-express calretinin. These results suggest that calretinin and glutamate receptor antibodies may be used to identify specific subsets of reticular formation neurons. RP Winsky, L (reprint author), NIMH,CLIN SCI LAB,RM 3D-48,10 CTR DR MSC 1266,BETHESDA,MD 20892, USA. NR 45 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 25 PY 1996 VL 741 IS 1-2 BP 123 EP 133 DI 10.1016/S0006-8993(96)00908-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA VZ081 UT WOS:A1996VZ08100017 PM 9001714 ER PT J AU Zappelli, F Willems, D Osada, S Ohno, S Wetsel, WC Molinaro, M Cossu, G Bouche, M AF Zappelli, F Willems, D Osada, S Ohno, S Wetsel, WC Molinaro, M Cossu, G Bouche, M TI The inhibition of differentiation caused by TGF beta in fetal myoblasts is dependent upon selective expression of PKC theta: A possible molecular basis for myoblast diversification during limb histogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; TRANSFORMING GROWTH-FACTOR; SKELETAL-MUSCLE; NPKC-THETA; MYOGENIC DIFFERENTIATION; CELL-DIFFERENTIATION; SIGNAL TRANSDUCTION; SATELLITE CELLS; GENE-EXPRESSION; MOUSE AB Embryonic and fetal skeletal myoblasts are responsible for the formation of primary and secondary fibers in mammals, but the mechanism which diversifies their fate is unknown. In vitro, embryonic myoblasts are resistant to the differentiation inhibitory effects of transforming growth factor beta and phorbol esters. Thus, differential expression of specific molecules involved in the transduction of extracellular signals may contribute to the different phenotypes. We report here that protein kinase C theta, but none of the other known protein kinase C isoforms, is selectively expressed in fetal and postnatal muscle cells (at both the myoblast and myotube stage) in vitro and in vivo. By contrast, embryonic myoblasts and myotubes do not express protein kinase C theta in vitro or in vivo. This difference is causally related to a differential response to transforming growth factor beta, since overexpression of protein kinase C theta, but not of protein kinase C alpha or zeta, in embryonic myoblasts makes these cells sensitive to transforming growth factor beta. These data demonstrate for the first time that a protein kinase C isoform is a key component of the signal transduction cascade which follows exposure of myoblasts to transforming growth factor beta. They also suggest a specific role for protein kinase C theta in determining the fate of different myoblasts during muscle histogenesis. (C) 1996 Academic Press, Inc. C1 UNIV ROMA TOR VERGATA,INST HISTOL & GEN EMBRYOL,I-00161 ROME,ITALY. YOKOHAMA CITY UNIV,SCH MED,DEPT MOL BIOL,YOKOHAMA,KANAGAWA 236,JAPAN. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC. RI Ohno, Shigeo/B-1768-2010 OI Ohno, Shigeo/0000-0002-1294-5269 FU Telethon [245] NR 47 TC 39 Z9 39 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 NOV 25 PY 1996 VL 180 IS 1 BP 156 EP 164 DI 10.1006/dbio.1996.0292 PG 9 WC Developmental Biology SC Developmental Biology GA VW700 UT WOS:A1996VW70000013 PM 8948582 ER EF