FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Spooner, KM Lane, HC Masur, H AF Spooner, KM Lane, HC Masur, H TI Guide to major clinical trials of antiretroviral therapy administered to patients infected with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; ZIDOVUDINE THERAPY; CUBIC MILLIMETER; HIV-1 INFECTION; DOUBLE-BLIND; DIDANOSINE; EFFICACY; AZT C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. NR 42 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1996 VL 23 IS 1 BP 15 EP 27 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UV502 UT WOS:A1996UV50200002 PM 8816123 ER PT J AU Hakansson, K Huh, C Grubb, A Karlsson, S Abrahamson, M AF Hakansson, K Huh, C Grubb, A Karlsson, S Abrahamson, M TI Mouse and rat cystatin C: Escherichia coli production, characterization and tissue distribution SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE cathepsin B; cysteine proteinase inhibitor; cysteine proteinases; E-coli expression; enzyme-linked immunosorbent assay; hereditary cystatin C amyloid angiopathy; amyloidosis ID CYSTEINE PROTEINASE-INHIBITOR; HEREDITARY CEREBRAL-HEMORRHAGE; AMINO-ACID-SEQUENCE; HUMAN GAMMA-TRACE; AMYLOID ANGIOPATHY; AFFINITY-CHROMATOGRAPHY; GEL ELECTROPHORESIS; BIOLOGICAL-FLUIDS; EXPRESSION; GENE AB Recombinant mouse (Mus musculus) and rat (Rattus norvegicus) cystatin C were produced by expression in Escherichia coli, isolated and functionally characterized. The mouse and rat inhibitors were both fully active in titrations of papain. Determination of equilibrium constants for dissociation (K-1) for their complexes with the target proteinase, cathepsin B, produced values not largely different from that for human cystatin C (K-1 0.07-0.13 nM). Rabbit antisera against mouse and rat cystatin C were produced and used for improved affinity purification of the recombinant inhibitors. Affinity purified immunoglobulins isolated from the antiserum against mouse cystatin C were used for construction of a sensitive enzyme-linked immunosorbent assay. The assay was used to demonstrate a high degree of immunological cross-reactivity between mouse and rat cystatin C and could be used for cystatin C quantification in mouse and rat tissue homogenates. All tissues analyzed contained cystatin C, with a relative content very similar to that of human tissues. For all species, brain tissue contained the highest cystatin C amounts and liver the lowest, whereas kidney, spleen and muscle tissues were intermediate in content. In the mouse, a notable high cystatin C content in parotid gland tissue was observed. The high degree of similarity in distribution pattern and functional properties for mouse, rat and human cystatin C indicates that a murine model should be relevant for studies of the human disease, hereditary cystatin C amyloid angiopathy. C1 UNIV LUND HOSP,INST LAB MED,DEPT CLIN CHEM,S-22185 LUND,SWEDEN. NINCDS,MOLEC & MED GENET SECT,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 52 TC 44 Z9 44 U1 0 U2 5 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 JUL PY 1996 VL 114 IS 3 BP 303 EP 311 DI 10.1016/0305-0491(96)00025-9 PG 9 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA VA465 UT WOS:A1996VA46500011 PM 8761177 ER PT J AU Thoma, GR Long, LR Berman, LE AF Thoma, GR Long, LR Berman, LE TI A client/server system for Internet access to biomedical text/image databanks SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE digitized medical X-rays; electronic X-ray archives; client server design; optical jukebox; RAID; image processing; multisocket transmission; Internet AB Internet access to mixed text/image databanks is finding application in the medical world. An example is a database of medical X-rays and associated data consisting of demographic, socioeconomic, physician's exam, medical laboratory and other information collected as part of a nationwide health survey conducted by the government. Another example is a collection of digitized cryosection images, CT and MR taken of cadavers as part of the National Library of Medicine's Visible Human Project. In both cases, the challenge is to provide access to both the images and the associated text for a wide end user community to create atlases, conduct epidemiological studies, to develop image-specific algorithms for compression, enhancement and other types of image processing, among many other applications. The databanks mentioned above are being created in prototype form. This paper describes the prototype system developed for the archiving of the data and the client software to enable a broad range of end users to access the archive, retrieve text and image data, display the data and manipulate the images. System design considerations include: data organization in a relational database management system with object-oriented extensions; a hierarchical organization of the image data by different resolution levels for different user classes; client design based on common hardware and software platforms incorporating SQL search capability, X Window, Motif and TAE (a development environment supporting rapid prototyping and management of graphic-oriented user interfaces); potential to include ultra high resolution display monitors as a user option; intuitive user interface paradigm for building complex queries; and contrast enhancement, magnification and mensuration tools for better viewing by the user. Copyright (C) 1996 Elsevier Science Ltd. RP Thoma, GR (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 13 TC 4 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JUL-AUG PY 1996 VL 20 IS 4 BP 259 EP 268 DI 10.1016/S0895-6111(96)00018-3 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW065 UT WOS:A1996VW06500008 PM 8954233 ER PT J AU Panksepp, J Knutson, B AF Panksepp, J Knutson, B TI Passion and reason: Making sense of our emotions - Lazarus,RS, Lazarus,BN SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review ID COGNITION C1 NIMH,POSTDOCTORAL PROGRAM,BETHESDA,MD 20892. RP Panksepp, J (reprint author), BOWLING GREEN STATE UNIV,BOWLING GREEN,OH 43403, USA. NR 6 TC 0 Z9 0 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD JUL PY 1996 VL 41 IS 7 BP 710 EP 711 PG 2 WC Psychology, Multidisciplinary SC Psychology GA UW965 UT WOS:A1996UW96500053 ER PT J AU Godin, PJ Buchman, TG AF Godin, PJ Buchman, TG TI Uncoupling of biological oscillators: A complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE multiple organ dysfunction; inflammatory response; systemic inflammatory response syndrome; pathogenicity; septic shock; endotoxin ID TUMOR-NECROSIS-FACTOR; PLACEBO-CONTROLLED TRIAL; HEART-RATE-VARIABILITY; HUMAN MONOCLONAL-ANTIBODY; GRAM-NEGATIVE BACTEREMIA; INTENSIVE-CARE UNIT; SEPTIC SHOCK; APPROXIMATE ENTROPY; ESCHERICHIA-COLI; SEPSIS SYNDROME AB Objective: To present a complementary hypothesis concern ing the pathogenesis of the multiple organ dysfunction syndrome, Data Sources: Primary reports and reviews published in peer-reviewed medical and scientific journals. Hypothesis: We suggest that healthy organs behave as biological oscillators, which couple to one another during human development, and that this orderly coupling is maintained through a communications network, including neural, humoral, and cytokine components, We suggest that the systemic inflammatory response syndrome initiates disruption of communication and uncoupling, and further suggest that progression into the multiple organ dysfunction syndrome reflects progressive uncoupling that can become irreversible, Resolution of the inflammatory response and reestablishment of the communications network are necessary but may not be, by itself, sufficient to allow organs to appropriately recouple, This hypothesis is testable using existing laboratory and clinical tools. C1 WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. NIH,BETHESDA,MD 20892. OI Buchman, Timothy/0000-0001-7350-5921 FU NIGMS NIH HHS [GM00581] NR 79 TC 217 Z9 221 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1996 VL 24 IS 7 BP 1107 EP 1116 DI 10.1097/00003246-199607000-00008 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA UX035 UT WOS:A1996UX03500008 PM 8674321 ER PT J AU Godin, PJ Fleisher, LA Eidsath, A Vandivier, RW Preas, HL Banks, SM Buchman, TG Suffredini, AF AF Godin, PJ Fleisher, LA Eidsath, A Vandivier, RW Preas, HL Banks, SM Buchman, TG Suffredini, AF TI Experimental human endotoxemia increases cardiac regularity: Results from a prospective, randomized, crossover trial SO CRITICAL CARE MEDICINE LA English DT Article DE heart rate; endotoxemia; approximate entropy; sepsis; multiple organ dysfunction syndrome; electrocardiography; endotoxin; critical illness; lipopolysaccharide; infection ID HEART-RATE-VARIABILITY; ACUTE MYOCARDIAL-INFARCTION; FREQUENCY-DOMAIN MEASURES; MULTIPLE-ORGAN FAILURE; APPROXIMATE ENTROPY; SPECTRAL-ANALYSIS; TIME-SERIES; ALGORITHM AB Objective: To determine whether human endotoxemia is associated with a loss of the physiologic beat-to beat variability of heart rate, Design: Prospective, randomized, crossover, single blind study, Setting: Clinical research center in a federal, nonuniversity hospital, Subjects: Healthy volunteers, Interventions,, Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen, Measurements and Main Results: Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs, Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy), Endotoxin administration was associated with loss of variability by all measures, This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin related symptoms. Conclusions: Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy, Changes in ap proximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis, This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems. C1 WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL,BALTIMORE,MD 21205. OI Buchman, Timothy/0000-0001-7350-5921 FU NIGMS NIH HHS [GM00581] NR 37 TC 144 Z9 146 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1996 VL 24 IS 7 BP 1117 EP 1124 DI 10.1097/00003246-199607000-00009 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA UX035 UT WOS:A1996UX03500009 PM 8674322 ER PT J AU Fox, PC Speight, PM AF Fox, PC Speight, PM TI Current concepts of autoimmune exocrinopathy - Immunologic mechanisms in the salivary pathology of Sjogren's syndrome SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE Sjogren's syndrome; salivary glands; immunology; cytokines ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; INFILTRATING T-CELLS; HEPATITIS-C VIRUS; BENIGN LYMPHOEPITHELIAL LESION; I TAX GENE; MALIGNANT-LYMPHOMA; GLAND BIOPSIES; RHEUMATOID-ARTHRITIS; MYOEPITHELIAL SIALADENITIS AB Sjogren's syndrome is a systemic autoimmune disorder characterized by symptoms of oral and ocular dryness and a chronic. progressive loss of salivary and lacrimal function. The exocrine involvement is the result of a focal, peri-ductal mononuclear cell infiltrate and the subsequent loss of secretory epithelial cells. The mechanisms of this autoimmune exocrinopathy are not understood fully. Many recent investigations have described alterations in a number of immune mediators within the salivary glands. These studies provide new insights into the immune regulation of normal salivary gland functions and the mechanisms of gland damage in Sjogren's syndrome. RP Fox, PC (reprint author), NIDR, CLIN INVEST & PATIENT CARE BRANCH, NIH, BLDG 10, ROOM 1N-113, BETHESDA, MD 20892 USA. NR 111 TC 91 Z9 92 U1 0 U2 4 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD JUL PY 1996 VL 7 IS 2 BP 144 EP 158 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VD472 UT WOS:A1996VD47200004 PM 8875029 ER PT J AU Lucas, B Germain, RN AF Lucas, B Germain, RN TI T-cell repertoire: Political correctness in the immune system SO CURRENT BIOLOGY LA English DT Article ID POSITIVE SELECTION AB Recent studies of T-cell development in various types of mutant mouse shed new light on the relative roles in T-cell selection of antigen verses MHC molecule recognition by T-cell receptors. RP Lucas, B (reprint author), NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 TC 6 Z9 6 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 1 PY 1996 VL 6 IS 7 BP 783 EP 787 DI 10.1016/S0960-9822(02)00594-8 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY128 UT WOS:A1996UY12800013 PM 8805292 ER PT J AU Beaven, MA AF Beaven, MA TI Calcium signalling: Sphingosine kinase versus phospholipase C? SO CURRENT BIOLOGY LA English DT Article ID SIMILAR MECHANISMS; RBL-2H3 CELLS; MAST-CELLS; 2H3 CELLS; ANTIGEN; EXOCYTOSIS; RELEASE; INFLUX; STORES; LINE AB A recent study shows that sphingosine kinase and its lipid product have an essential signalling function; they act, in the mobilization of calcium ions in antigen stimulated mast cells, This finding may have relevance to signalling in other cells of the immune system. RP Beaven, MA (reprint author), NHLBI,LAB MOL IMMUNOL,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 14 TC 25 Z9 25 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 1 PY 1996 VL 6 IS 7 BP 798 EP 801 DI 10.1016/S0960-9822(02)00598-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY128 UT WOS:A1996UY12800017 PM 8805291 ER PT J AU Qin, CA Tumminia, SJ Russell, P Rao, PV Zigler, JS AF Qin, CA Tumminia, SJ Russell, P Rao, PV Zigler, JS TI Investigations into the loss of glutathione from lenses in organ culture SO CURRENT EYE RESEARCH LA English DT Article DE glutathione; lens; 2-mercaptoethanol; organ culture; rats ID OXIDATIVE STRESS; INDUCED CATARACT; RAT LENSES; METABOLISM; INVITRO; DISULFIDE; MODEL; H2O2 AB Purpose. To investigate possible causes and implications of the decrease in glutathione concentration in rat lenses during organ culture. Methods. Freshly excised lenses were incubated in modified TC-199 medium. Ellman's Reagent or the GSH-400 assay were used to assay glutathione levels in lenses cultured for different times and under a variety of altered culture conditions. Results. In lenses from young rats the glutathione decrease was not ameliorated by reduction of oxygen tension in the incubator, nor by supplementation of the culture medium with various antioxidants or sulfhydryl compounds, nor with the amino acid precursors of glutathione. Addition of 2-mercaptoethanol stimulated cysteine transport into the lens but had only a modest effect in maintaining the level of glutathione. The decrease in glutathione concentration was less in cultured lenses from older rats. Lenses from rhesus monkeys exhibited no decrease in glutathione levels when maintained in organ culture for up to 48 h. Conclusions. The basis for the decreased glutathione in cultured young rat lenses is still uncertain. The data from the present study indicate a definite relationship between glutathione loss and age for cultured rat lenses, with young lenses being much more susceptible. The resistance of cultured monkey lenses to loss of glutathione demonstrates species differences in this property which may be relevant to previously reported differences in susceptibility to oxidative damage. C1 NEI,LAB MECHANISMS OCULAR DIS,NIH,BETHESDA,MD 20892. NR 33 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUL PY 1996 VL 15 IS 7 BP 719 EP 725 DI 10.3109/02713689609003454 PG 7 WC Ophthalmology SC Ophthalmology GA UZ340 UT WOS:A1996UZ34000004 PM 8670779 ER PT J AU Lebowitz, BD AF Lebowitz, BD TI Community services for elderly people SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID SPOUSE-CAREGIVERS; LATE-LIFE; CARE; DEPRESSION; QUALITY; TRIAL AB Developments and research on community services for older people with mental disorders are reviewed within an environment of health care system reform in the USA. The focus is on five issues: the growing importance of managed care; the enhanced significance of primary care; the place of comprehensive assessment; the redefinition of outcomes; the clarification of the role of the family and of the institution. RP Lebowitz, BD (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,5600 FISHERS LANE,ROOM 18-101,ROCKVILLE,MD 20857, USA. NR 28 TC 3 Z9 3 U1 2 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JUL PY 1996 VL 9 IS 4 BP 294 EP 297 DI 10.1097/00001504-199607000-00013 PG 4 WC Psychiatry SC Psychiatry GA UY849 UT WOS:A1996UY84900013 ER PT J AU ZahnWaxler, C AF ZahnWaxler, C TI Environment, biology, and culture: Implications for adolescent development SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID SOCIALIZATION; CHILDHOOD; GENDER AB This special issue, ''Development, Transitions, and Adjustment in Adolescence,'' examines the roles of socialization, biology, and culture as they bear on adaptive and maladaptive developmental outcomes. Problems of adolescence that are addressed include, but are not restricted to, antisocial behavior, depressive symptoms, substance abuse, low achievement, and eating problems. Factors implicated in successful adaptation, as well as psychopathology, are considered, with an emphasis on both risk and protection. The investigations and commentaries highlight conceptual and methodological progress in understanding variations in patterns of adjustment as adolescents move toward assumption of adult roles. Limitations in the current knowledge base also are indicated, which may serve to inform future theoretical and empirical work on adolescent development. RP ZahnWaxler, C (reprint author), NIMH,SECT DEV PSYCHOPATHOL,15-K 9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 12 Z9 13 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 1996 VL 32 IS 4 BP 571 EP 573 PG 3 WC Psychology, Developmental SC Psychology GA UW869 UT WOS:A1996UW86900001 ER PT J AU Considine, RV Considine, EL Williams, CJ Hyde, TM Caro, JF AF Considine, RV Considine, EL Williams, CJ Hyde, TM Caro, JF TI The hypothalamic leptin receptor in humans - Identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations SO DIABETES LA English DT Article AB Leptin-receptor gene expression in hypothalamic tissue from lean and obese humans was examined. The full-length leptin receptor, that is believed to transmit the leptin signal, is expressed in human hypothalamus. There was no difference in the amount of leptin-receptor mRNA in seven lean (BMI 23.3 +/- 0.9 kg/m(2)) and eight obese (BMI 36.9 +/- 1.5) subjects as determined by reverse transcription-polymerase chain reaction, A sequence polymorphism (A-->G) was detected at position 668 of the leptin receptor cDNA, This second base substitution changed a glutamine to an arginine at position 223 of the leptin receptor protein. Of 15 subjects analyzed, 11 were heterozygous for this base change and 3 were homozygous, The occurance of the polymorphic allele(s) did not correlate with BMI in the population studied. The mutation responsible for the defect in the leptin receptor in db/db mice was not detected in any obese human, nor was the fa/fa rat mutation. These results provide evidence that the leptin resistance observed in obese humans is not due to a defect in the leptin receptor. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,WASHINGTON,DC. RP Considine, RV (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,DIV ENDOCRINOL & METAB,1025 WALNUT ST,PHILADELPHIA,PA 19107, USA. FU NIDDK NIH HHS [R01-DK45592] NR 15 TC 144 Z9 158 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 IS 7 BP 992 EP 994 DI 10.2337/diabetes.45.7.992 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UU168 UT WOS:A1996UU16800024 PM 8666155 ER PT J AU Howard, BV Lee, ET Fabsitz, RR Robbins, DC Yeh, JLL Cowan, LD Welty, TK AF Howard, BV Lee, ET Fabsitz, RR Robbins, DC Yeh, JLL Cowan, LD Welty, TK TI Diabetes and coronary heart disease in American Indians - The Strong Heart Study SO DIABETES LA English DT Article; Proceedings Paper CT 15th International-Diabetes-Federation Satellite Symposium on Diabetes and Macrovascular Complications CY NOV 12-13, 1994 CL OSAKA, JAPAN SP Int Diabet Federat, Multiclin Study Grp Diabet Macroangiopathy, Japan Cardiovasc Res Fdn, Japan Diabet Soc, Japan Atherosclerosis Soc ID ACUTE MYOCARDIAL-INFARCTION; IMPAIRED GLUCOSE-TOLERANCE; NON-HISPANIC WHITES; CARDIOVASCULAR-DISEASE; MEXICAN-AMERICANS; NAVAJO INDIANS; BLOOD-PRESSURE; SIOUX INDIANS; RISK-FACTORS; HYPERTENSION AB Coronary heart disease (CHD) is the leading cause of death among American Indians, However, information on the prevalence of CHD and its association with known risk factors is Limited, The purpose of the Strong Heart Study is to quantify CHD and its risk factors among three geographically diverse groups of American Indians, The population consists of 4,549 adults between 45 and 74 years of age in 13 Indian communities in Arizona, Oklahoma, and South and North Dakota. The phase I examination (1989-1991) revealed very high prevalence rates of diabetes that ranged from 33 to 72% in men and women in the three centers, Prevalence rates of definite myocardial infarction (MI) and definite CHD mere higher in men than in women in all three centers (P < 0.0001) and in these with diabetes (P = 0.002 and P = 0.0003 in women and men, respectively). Diabetes was associated with a relatively greater increase in prevalence of MI (prevalence rate = 3.8 vs, 1.9) and CHD (prevalence rate = 4.6 vs, 1.8) in women than in men, Logistic regression analysis indicated that the prevalence of CHD among American Indians was significantly related to age, diabetes, hypertension, albuminuria, percentage of body fat, smoking, high concentrations of plasma insulin, and low concentrations of HDL cholesterol, Lower prevalence rates of CND were found in Arizona despite higher rates of diabetes, obesity, hypertension, and albuminuria; these lower rates may be in part related to lower smoking frequency and lower concentrations of total and LDL cholesterol, These findings from the baseline Strong Heart Study examination emphasize the relative importance of diabetes and its associated variables as risk factors for CHD among American Indian populations. C1 UNIV OKLAHOMA,HLTH SCI CTR,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK. UNIV OKLAHOMA,HLTH SCI CTR,DEPT BIOSTAT & EPIDEMIOL,OKLAHOMA CITY,OK. NHLBI,NIH,BETHESDA,MD 20892. ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD. RP Howard, BV (reprint author), MEDLANT RES INST,108 IRVING ST NW,WASHINGTON,DC 20010, USA. NR 48 TC 30 Z9 30 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 SU 3 BP S6 EP S13 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV115 UT WOS:A1996UV11500001 PM 8674894 ER PT J AU Mayfield, JA Reiber, GE Nelson, RG Greene, T AF Mayfield, JA Reiber, GE Nelson, RG Greene, T TI A foot risk classification system to predict diabetic amputation in Pima Indians SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY AMPUTATIONS; MANAGEMENT; MELLITUS; DISEASE AB OBJECTIVE - To quantify the contribution of various risk factors to the risk of amputation in diabetic patients and to develop a foot risk scoring system based on clinical data. RESEARCH DESIGN AND METHODS - A population-based case-control study was undertaken. Eligible subjects were 1) 25-85 years of age, 2) diabetic, 3) 50% or more Pima or Tohono O'odham Indian, 4) lived in the Gila River Indian Community, and 5) had had at least one National Institutes of Health research examination. Case patients had had an incident lower extremity amputation between 1983 and 1992; control subjects had no amputation by 1992. Medical records were reviewed to determine risk conditions and health status before the pivotal event that led to the amputation. RESULTS - Sixty-one people with amputations were identified and compared with 183 control subjects. Men were more likely to suffer amputation than women (odds ratio [OR] 6.5, 95% CI 2.6-15), and people with diabetic eye, renal, or cardiovascular disease were more likely to undergo amputation than those without (OR 4.6, 95% CI 1.7-12). The risk of amputation was almost equally associated with these foot risk factors. peripheral neuropathy, peripheral vascular disease, bony deformities, and a history of foot ulcers. After controlling for demographic differences and diabetes severity, the ORs for amputation with one loot risk factor was 2.1 (95% CI 1.4-3.3), with two risk factors, 4.5 (95% CI 2.9-6.9), and with three or four risk factors, 9.7 (95% CI 6.3-14.8). CONCLUSIONS - Male sex, end-organ complications of eye, heart, and kidney, and poor glucose control were associated with a higher amputation rate. Peripheral neuropathy, peripheral vascular disease, deformity, and a prior ulcer were similarly equally associated with an increased risk of lower extremity amputation. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,HLTH SERV RES,SEATTLE,WA. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RP Mayfield, JA (reprint author), INDIANA UNIV,LONG HOSP,DEPT FAMILY PRACTICE,BOWEN RES CTR,1110 W MICHIGAN ST,ROOM 200,INDIANAPOLIS,IN 46202, USA. RI Nelson, Robert/B-1470-2012 FU AHRQ HHS [HS-07238] NR 28 TC 48 Z9 54 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1996 VL 19 IS 7 BP 704 EP 709 DI 10.2337/diacare.19.7.704 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT646 UT WOS:A1996UT64600003 PM 8799623 ER PT J AU Sievers, ML Nelson, RG Bennett, PH AF Sievers, ML Nelson, RG Bennett, PH TI Decrease in mortality from diabetic nephropathy in Pima Indians SO DIABETES CARE LA English DT Letter RP Sievers, ML (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Nelson, Robert/B-1470-2012 NR 1 TC 4 Z9 4 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1996 VL 19 IS 7 BP 777 EP 777 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT646 UT WOS:A1996UT64600020 PM 8799640 ER PT J AU Abati, A AF Abati, A TI Uniform approach to breast aspirates: The quest becomes reality SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material RP Abati, A (reprint author), NCI,CYTOPATHOL SECT,NATL INST HLTH,BLDG 10,ROOM 2A19,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUL PY 1996 VL 15 IS 1 BP R7 EP R8 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA UU374 UT WOS:A1996UU37400001 PM 8807243 ER PT J AU Ayyavoo, V Ugen, KE Fernandes, LS Goedert, JJ Rubinstein, A Williams, WV Weiner, DB AF Ayyavoo, V Ugen, KE Fernandes, LS Goedert, JJ Rubinstein, A Williams, WV Weiner, DB TI Analysis of genetic heterogeneity, antigenicity, and biological characteristics of HIV-1 in a maternal transmitter and nontransmitter patient pair SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRINCIPAL NEUTRALIZING DOMAIN; SEQUENCE VARIATION; VERTICAL TRANSMISSION; INFANT TRANSMISSION; V3 LOOP; TYPE-1; ANTIBODIES; INFECTION; CHIMPANZEES AB To obtain insight into the factors involved in vertical transmission, we compared the sequence diversity, seroreactivity, and biological characteristics of human immunodeficiency virus type 1 (HIV-1) derived from a transmitter and nontransmitter mother pair. Forty-two clones from the transmitter and 20 from the nontransmitter, spanning the principal neutralization determinant (PND) of the env gene, were sequenced and analyzed. The intrapatient sequence variation in transmitter and nontransmitter viruses was 12% and 36%, respectively, and the interpatient variation was 38%. In an effort to correlate immune responses to viral genetics, we analyzed the sera from these patients against a number of V3 peptides from known HIV-1 isolates, We observed that (i) both the transmitter and nontransmitter sera demonstrated higher binding to V3 peptides based on SF-2 and MN sequences than to IIIB and Z6 isolates; (ii) the vertical transmission of HIV-1 is correlated with the absence of high maternal antibody responses to the PND; and (iii) the high-affinity binding of the sera to SF-2 and MN V3 peptides correlated with the sequence analysis, indicating that the V3 sequences from both patients are more closely related to ADA, SF-162, and MN than to IIIB or Z6. Biological analysis of the viruses from these patients demonstrate that the transmitters' viruses infect a number of T-cell lines in vitro, whereas the nontransmitter viruses do not infect cell lines or the primary lymphocytes. C1 UNIV PENN,DEPT PATHOL & LAB MED,IBAMM,PHILADELPHIA,PA 19014. NCI,LAB VIRAL EPIDEMIOL,ROCKVILLE,MD 20852. ALBERT EINSTEIN COLL MED,BRONX,NY 10461. RI Ugen, Kenneth/H-6544-2011; Weiner, David/H-8579-2014; OI Ayyavoo, Velpandi/0000-0002-9043-0885 NR 40 TC 5 Z9 5 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 JUL PY 1996 VL 15 IS 7 BP 571 EP 580 DI 10.1089/dna.1996.15.571 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA VC094 UT WOS:A1996VC09400006 PM 8756338 ER PT J AU Shoaib, M AF Shoaib, M TI Determinants of nicotine self-administration SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 1st Annual Duke-University Nicotine Research Conference CY NOV 08-09, 1995 CL DURHAM, NC SP Duke Univ DE reinforcement; genetics; species; schedules; route; infusion ID FOOD DELIVERY SCHEDULE; SENSITIZES RATS; BODY-WEIGHT; COCAINE; ADDICTION; CAFFEINE; TOBACCO; REINFORCEMENT; ACQUISITION; PREEXPOSURE AB Experiments utilizing the self-administration procedure have yielded varied rates of responding when using nicotine as the reinforcer. A number of factors are reviewed that appear to determine behavioral performance in self-administration procedures. Species differences ranging from rats to human, genotypic differences, schedules of reinforcement, food deprivation, routes of administration, rates of nicotine infusion, and previous drug history are all critical determinants of nicotine self-administration. Further characterization of these factors will be necessary in order to establish a ''threshold dose'' of nicotine as a means of regulating nicotine addiction. (C) 1996 Wiley-Liss, Inc. RP Shoaib, M (reprint author), NIDA,PRECLIN PHARMACOL LAB,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224, USA. NR 56 TC 6 Z9 6 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUL-AUG PY 1996 VL 38 IS 3-4 BP 212 EP 221 DI 10.1002/(SICI)1098-2299(199607/08)38:3/4<212::AID-DDR10>3.0.CO;2-0 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WA754 UT WOS:A1996WA75400010 ER PT J AU Soltis, MJ Yeh, HJ Cole, KA Whittaker, N Wersto, RP Kohn, EC AF Soltis, MJ Yeh, HJ Cole, KA Whittaker, N Wersto, RP Kohn, EC TI Identification and characterization of human metabolites of CAI[5-amino-1-1(4'-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole-4-ca rboxamide) SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CALCIUM INFLUX; RECEPTOR; L651582; SIGNAL; AGENT AB The calcium influx inhibitor and cytostatic agent, 5-amino-1-1(4'-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide (CAI), is in phase I clinical trial for patients with refractory cancer. Additional chromatography peaks were observed during HPLC analysis of patient samples. Identification and characterization of physiological metabolites were undertaken using HPLC techniques developed for their purification from blood, pleural fluid, and urine samples. A hydrophobic metabolite, M1, was purified and functionally characterized. Structural analysis of the purified compound indicated that it is a 3,5-dichloro-4(p-chlorobenzoyl)benzoic acid. Quantitative analysis of M1 concentration during CAI administration indicated that the rise in M1 concentration lagged behind that of CAI and persisted after CAI was no longer detectable. No clear relationship between CAI or M1 and either toxicity or efficacy was observed. Chromatography of patient blood and urine samples under conditions favoring hydrophilic metabolite detection suggested the presence of a glucuronide compound; this was also indicated by sample treatment with beta-glucuronidase. Attempts at purification did not yield a compound stable for structural analysis. The benzophenone metabolite, M1, was nonfunctional in assays of calcium influx inhibition or proliferation. No pharmacodynamic associations were observed for these metabolites, nor was there pharmacological activity of the M1 as an individual agent. These data suggest that CAI is processed into triazole and benzophenone moieties by phase I metabolism, and these metabolites or the parent compound may be conjugated for excretion by glucuronidation. C1 NCI,SIGNAL TRANSDUCT & PREVENT UNIT,PATHOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,ANALYT CHEM LAB,BETHESDA,MD. RI Cole, Kristina/M-3922-2015 NR 16 TC 65 Z9 65 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 1996 VL 24 IS 7 BP 799 EP 806 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UW900 UT WOS:A1996UW90000016 PM 8818579 ER PT J AU Conner, EA Wirth, PJ AF Conner, EA Wirth, PJ TI Protein alterations associated with gene amplification in cultured human and rodent cells SO ELECTROPHORESIS LA English DT Article DE gene amplification; N-(phosphonacetyl-L-asparate); carbamyl p-synthetase; aspartate transcarbamylase and dihydroorotase gene; immobilized pH gradients; two-dimensional polyacrylamide gel electrophoresis ID IMMOBILIZED PH GRADIENTS; POLYACRYLAMIDE-GEL ELECTROPHORESIS; FIBROBLAST GROWTH-FACTOR; DRUG-RESISTANCE; 2-DIMENSIONAL ELECTROPHORESIS; LINES; P53; EXPRESSION; RETINOBLASTOMA; RESOLUTION AB Genomic stability was investigated in Chinese hamster ovary (CHO) and human hepatocellular carcinoma HepG2 cells selected for growth in the presence of cytotoxic concentrations of N-(phosphonacetyl-L-asparate) (PALA). In CHO cells selected with 9 x LD(50) PALA the carbamyl p-synthetase, aspartate transcarbamylase and dihydroorotase (CAD) gene complex was amplified two-fold while in HepG2 cells selected at comparable PALA concentrations a 7- to 10-fold increase in the CAD gene was observed. Concomitant with amplification of the CAD gene were increases in CAD mRNA and protein expression in both CHO and HepG2 cells. In long-term cultures of HepG2 cells the CAD gene underwent spontaneous amplification (5-fold) in the absence of PALA treatment with increasing passage number. In an attempt to define proteins and/or family of proteins that may either directly or indirectly influence DNA amplification potential through a mechanism of enhanced genomic instability, immobilized pH gradient-two-dimensional polyacrylamide gel electrophoresis (IPG 2-D PAGE) analysis of silver-stained nuclear cytoplasmic polypeptides comcomitant with PALA resistance and CAD amplification was performed. Analysis of silver-stained polypeptides from 3 x LD(50) PALA-selected CHO and HepG2 cells revealed no significant alterations in polypeptide expression. In CHO cells selected at 5 x and 7 x PALA LD(50), and HepG2 cells selected at 5 x and 9 x PALA LD(50), one subset of 4-8 polypeptides (pI: pI 7.2-7.6/36-38 kDa) were increased 2- to 3-fold in both 5 x and 7 x- and 5 x and 9 x LD(50) PALA-selected CHO and HepG2, respectively, while five relatively neutral-to-basic, low M(r) polypeptides (p2: 18/7.30; p3: 16/7.00; p4: 14/7.00; p5: 14/7.40; and p6: 13.5/7.00) were markedly increased in CHO cells selected at 7 x LD(50) PALA. In addition to these PALA-associated increases, four polypeptides (p7a: pI 6.50/40 kDa; p7b: 6.55/40; p7c: 6.60/40; and p7d: 6.65/40) were significantly increased in high-passage (p159) HepG2 cells undergoing spontaneous CAD gene amplification in the absence of PALA exposure. In CHO cells, polypeptides p7 a, b, d were increased while the expression of p7c (pI 6.60/40 kDa) was unaltered in 7 x LD(50)-treated CHO cells. Although neither the identity nor biological function of polypeptides 1-7 is known, a proposed mechanism involving interaction with certain growth regulatory proteins such as p53 for mediating genomic instability is given. C1 NCI,PROT RES GRP,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 46 TC 3 Z9 3 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1996 VL 17 IS 7 BP 1257 EP 1264 DI 10.1002/elps.1150170715 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VA270 UT WOS:A1996VA27000014 PM 8855414 ER PT J AU YamaguchiIwai, Y Stearman, R Dancis, A Klausner, RD AF YamaguchiIwai, Y Stearman, R Dancis, A Klausner, RD TI Iron-regulated DNA binding by the AFT1 protein controls the iron regulon in yeast SO EMBO JOURNAL LA English DT Article DE AFT1; consensus sequence; iron metabolism; transcription factor; yeast ID SACCHAROMYCES-CEREVISIAE; GENE; RNA; EXPRESSION; LACZ AB Iron deprivation of Saccharomyces cerevisiae induces transcription of genes required for high-affinity iron uptake. AFT1 mediates this transcriptional control. In this report, the 5'-flanking region of FET3, which encodes a copper-dependent oxidase required for iron transport, was analyzed and found to contain a DNA sequence responsible for AFT1-regulated gene expression. AFT1 was capable of interacting specifically with this DNA sequence. A core element within this DNA sequence necessary for the binding of AFT1 was also determined. In vivo footprinting demonstrated occupancy of the AFT1 binding site in cells deprived of iron and not in cells grown in the presence of iron. Thus, the environmental signal resulting from iron deprivation was transduced through the regulated binding of AFT1 to the FET3 promoter, followed by the activation of transcription. A regulon of genes under the control of AFT1 could be defined. AFT1 was able to bind to a consensus binding site (PyPuCAC-CCPu) in the 5' region of FRE1, FRE2, FTR1, FTH1 and CCC2. C1 NICHHD, CELL BIOL & METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NR 29 TC 256 Z9 258 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD JUL 1 PY 1996 VL 15 IS 13 BP 3377 EP 3384 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UW668 UT WOS:A1996UW66800019 PM 8670839 ER PT J AU Franzoso, G Carlson, L Brown, K Daucher, MB Bressler, P Siebenlist, U AF Franzoso, G Carlson, L Brown, K Daucher, MB Bressler, P Siebenlist, U TI Activation of the serum response factor by p65/NF-kappa B SO EMBO JOURNAL LA English DT Article DE accessory factors; NF-kappa B; p65; serum response factor; transcriptional regulation ID NF-KAPPA-B; TERNARY COMPLEX-FORMATION; ALPHA-CHAIN GENE; C-FOS PROMOTER; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; ONCOPROTEIN BCL-3; PROTEIN ELK-1; FACTOR P62TCF; SRF AB This study demonstrates that the NF-kappa B subunit p65 can act like an accessory protein for the serum response factor (SRF) in transfection assays. p65 functionally synergizes with SRF to activate the transcription of a reporter construct dependent only on the serum response element (SRE). The synergy of the two factors requires neither a kappa B motif nor direct contact of p65 with DNA. Consistent with these results, a physical complex containing p65 and SRF is observed in vitro. Synergy of the factors is independent of the previously described activation domains present on p65, ruling out indirect effects of p65, but synergy is dependent on the activation domain of SRF. The complexing of p65 and SRF is mediated by a segment of the SRF DNA binding domain, a region of the protein which has also been reported to inhibit its own activation domain. We speculate that p65, upon direct or facilitated interaction with SRF, may relieve the inhibitory activity of this segment, thus enabling the activation domain of SRF to become fully functional. In contrast to p65, the p50 subunit of NF-kappa B does not interact significantly with SRF, either functionally or physically. The data suggest the intriguing possibility that NF-kappa B may participate in the regulation of SRE-dependent promoters, expanding the range of activities of this rapidly activatable transcription factor. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NR 70 TC 47 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 1 PY 1996 VL 15 IS 13 BP 3403 EP 3412 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UW668 UT WOS:A1996UW66800022 PM 8670842 ER PT J AU Fedorko, DP Hijazi, YM AF Fedorko, DP Hijazi, YM TI Application of molecular techniques to the diagnosis of microsporidial infection SO EMERGING INFECTIOUS DISEASES LA English DT Article ID RIBOSOMAL-RNA SEQUENCE; HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; ENCEPHALITOZOON-CUNICULI; ENTEROCYTOZOON-BIENEUSI; INTESTINAL MICROSPORIDIOSIS; AIDS PATIENTS; N-SP; IDENTIFICATION; DIARRHEA AB Microsporidia are now recognized as important pathogens of AIDS patients; the ability of these parasites to cause disease in immunocompetent persons is still being elucidated. Improved diagnostic tests for microsporidial infection are continually being sought for establishing diagnosis in order to avoid laborious electron microscopy studies that require invasively acquired biopsy specimens. Modified trichrome or chemofluorescent stains are useful for detecting microsporidia in bodily fluids and stool specimens, but they do not allow for speciation of microsporidia. Polymerase chain reaction with specific primers will allow the detection and speciation of microsporidia in biopsy tissue, bodily fluids, and stool specimens. RP Fedorko, DP (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 44 TC 56 Z9 57 U1 1 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL-SEP PY 1996 VL 2 IS 3 BP 183 EP 191 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VA263 UT WOS:A1996VA26300004 PM 8903228 ER PT J AU Behar, V Pines, M Nakamoto, C Greenberg, Z Bisello, A Stueckle, SM Bessalle, R Usdin, TB Chorev, M Rosenblatt, M Suva, LJ AF Behar, V Pines, M Nakamoto, C Greenberg, Z Bisello, A Stueckle, SM Bessalle, R Usdin, TB Chorev, M Rosenblatt, M Suva, LJ TI The human PTH2 receptor: Binding and signal transduction properties of the stably expressed recombinant receptor SO ENDOCRINOLOGY LA English DT Article ID HUMAN PARATHYROID-HORMONE; ALKALINE-PHOSPHATASE ACTIVITY; OSTEO-SARCOMA CELLS; FUNCTIONAL EXPRESSION; FREE CALCIUM; CLONING; PROTEIN; PEPTIDE; REGION; BONE AB We have generated a series of stably transfected HEK-293 cell lines expressing the newly identified alternate human PTH receptor (hPTH2 receptor). This receptor subtype is selectively activated by N-terminal PTH-(1-34) and not the corresponding N-terminal (1-34) region of the functionally and structurally related hormone, PTH-related protein (PTHrP). A total of 20 distinct clones displaying different levels of PTH-responsive cAMP production were analyzed. None responded to PTHrP-(1-34). One of these clones (BP-16), displaying maximal PTH responsiveness, was chosen for more detailed evaluation. The BP-16 clone (and the parental HEK-293 cell line lacking both the hPTH/PTHrP receptor and the hPTH2 receptor) were examined for PTH binding, PTH-stimulated cAMP accumulation, PTH-stimulated changes in intracellular calcium ([Ca2+](i)) levels, and hPTH2 receptor messenger RNA expression. In addition, we studied the photomediated cross-linking of a potent PTH agonist, namely [Nle(8,18),Lys(13)(epsilon-pBz(2)),2-L-Nal(23),Tyr(34)]bPTH(1-34)NH2 (K13), to the hPTH2 receptor on BP-16 cells. Photoaffinity cross-linking identified an similar to 90-kDa cell membrane component that was specifically competed by PTH-(1-34) and other receptor-interacting ligands. PTH-(1-34) and K13 are potent stimulators of both cAMP accumulation and increases in [Ca2+](i) levels, and both bind to the hPTH2 receptor with high affinity (apparent K-d, 2.8 +/- 0.9 x 10(-8) and 8.5 +/- 1.7 x 10(-8) M, respectively). There was no apparent binding, cAMP-stimulating activity, or [Ca2+](i) signaling observed, nor was specific competition vs. binding of a PTH-(1-34) radioligand ([I-125]PTH) with PTHrP-(1-34)-NH2 found. PTHrP-(1-34) failed to inhibit cross-linking of the hPTH2 receptor by radiolabeled K13 ([I-125]K13). However, effective competition vs. [I-125]PTH and [I-125]K13 binding and [125I]K13 cross-linking were observed with the potent PTH/PTHrP receptor antagonists, PTHrP-(7-34)NH2 and PTH-(7-34)NH2. PTHrP-(7-34)NH2 was shown to be a partial agonist that weakly stimulates both cAMP accumulation and increases in [Ca2+](i) levels in BP-16 cells. These data suggest that the hPTH2 receptor is distinct from the hPTH/PTHrP receptor in the structural features it requires for ligand binding in the family of PTH and PTHrP peptides. C1 BETH ISRAEL HOSP, DEPT MED, HARVARD THORNDIKE & CHARLES A DANA LABS, DIV BONE & MINERAL METAB, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [DK-47940] NR 48 TC 73 Z9 73 U1 0 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 JUL PY 1996 VL 137 IS 7 BP 2748 EP 2757 DI 10.1210/en.137.7.2748 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UR955 UT WOS:A1996UR95500014 PM 8770894 ER PT J AU Roseboom, PH Coon, SL Baler, R McCune, SK Weller, JL Klein, DC AF Roseboom, PH Coon, SL Baler, R McCune, SK Weller, JL Klein, DC TI Melatonin synthesis: Analysis of the more than 150-fold nocturnal increase in serotonin N-acetyltransferase messenger ribonucleic acid in the rat pineal gland SO ENDOCRINOLOGY LA English DT Article ID CIRCADIAN-RHYTHM; ADENOSINE 3',5'-MONOPHOSPHATE; ADRENERGIC REGULATION; ORGAN-CULTURE; STIMULATION; RNA; ADENOSINE-3',5'-MONOPHOSPHATE; EXPRESSION; DECREASE; RECEPTOR AB In vertebrates, the circadian rhythm in the activity of serotonin N-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87] drives the daily rhythm in circulating melatonin. We have discovered that expression of the AA-NAT gene in the rat pineal gland is essentially turned off during the day and turned on at night, resulting in a more than 150-fold rhythm. Expression is regulated by a photoneural system that acts through an adrenergic-cAMP mechanism in pinealocytes, probably involving cAMP response element-binding protein phosphorylation. Turning off AA-NAT expression appears to involve de novo synthesis of a protein that attenuates transcription. A similar to 10-fold night/day rhythm in AA-NAT messenger RNA occurs in the retina, and AA-NAT messenger RNA is also detected at low levels in the brain. C1 NICHHD, SECT NEUROENDOCRINOL, DEV NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, DIV NEONATOL, BALTIMORE, MD 21287 USA. NR 47 TC 250 Z9 255 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1996 VL 137 IS 7 BP 3033 EP 3044 DI 10.1210/en.137.7.3033 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UR955 UT WOS:A1996UR95500049 PM 8770929 ER PT J AU Otonkoski, T Cirulli, V Beattie, GM Mally, MI Soto, G Rubin, JS Hayek, A AF Otonkoski, T Cirulli, V Beattie, GM Mally, MI Soto, G Rubin, JS Hayek, A TI A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced pancreatic beta-cell growth SO ENDOCRINOLOGY LA English DT Article ID SCATTER FACTOR; TISSUE-CULTURE; EPITHELIAL-CELLS; TYROSINE KINASE; RECEPTOR; CLUSTERS; RNA; RAT; SEQUENCE; INSULIN AB We have investigated the role of hepatocyte growth factor/scatter factor (HGF/SF) in the growth and/or differentiation of pancreatic islet beta-cells. We found that in the human fetal pancreas immunoreactive HGF/SF receptor (c-met proto-oncogene product) is preferentially associated with the developing beta-cells. In the adult pancreas, c-met messenger RNA is highly enriched in the islets and the immunoreactive protein is also restricted to the islet beta-cells. HGF/SF messenger RNA content of fetal pancreas-derived fibroblasts is more than 10-fold higher than that of adult fibroblasts. Culture of human fetal pancreatic epithelial cells in conditioned medium from the fetal pancreatic fibroblasts caused a 2.4-fold stimulation of the formation of islet-like cell clusters that was due to both mitogenic and morphogenic effects. beta-cell proliferation in the cell clusters was stimulated 3.5-fold by the conditioned medium, and this was associated with a marked decrease in insulin content. All of the effects of the conditioned medium were blocked by anti-HGF/SF antibody. Specificity was confirmed by overriding the blocking effect of the antibody with excess recombinant HGF/SF. Conditioned medium from adult pancreatic fibroblasts stimulated islet-like cell cluster formation only slightly, and did not affect beta-cell replication. These results suggest that HGF/SF secreted by fetal fibroblasts is mitogenic to beta-cells. Taken together, our findings indicate an important role for HGF/SF in fetal mesenchyme-induced pancreatic beta-cell growth. C1 UNIV CALIF SAN DIEGO, SCH MED, WHITTIER INST, DEPT PEDIAT, LA JOLLA, CA 92037 USA. HELSINKI UNIV, CHILDRENS HOSP, FIN-00014 HELSINKI, FINLAND. HELSINKI UNIV, TRANSPLANTAT LAB, FIN-00014 HELSINKI, FINLAND. UNIV CALIF SAN DIEGO, NATL CTR MICROSCOPY & IMAGING RES, LA JOLLA, CA 92093 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RI Otonkoski, Timo/F-1189-2011 FU NCRR NIH HHS [RR-04050]; NIDDK NIH HHS [R01-DK 39087]; NIGMS NIH HHS [2SO6 GM-47165-05] NR 40 TC 103 Z9 106 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1996 VL 137 IS 7 BP 3131 EP 3139 DI 10.1210/en.137.7.3131 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UR955 UT WOS:A1996UR95500059 PM 8770939 ER PT J AU Rowland, AS Baird, DD Shore, DL Darden, B Wilcox, AJ AF Rowland, AS Baird, DD Shore, DL Darden, B Wilcox, AJ TI Ethylene oxide exposure may increase the risk of spontaneous abortion, preterm birth, and postterm birth SO EPIDEMIOLOGY LA English DT Article DE ethylene oxide; spontaneous abortion; occupational diseases; prematurity; postterm; cohort studies; dental staff; postmature infant; premature infant AB Ethylene oxide is a gas used in some dental offices to sterilize equipment. In pregnant laboratory animals, ethylene oxide increases malformations and fetal loss. Increased gestation length has also been reported. In humans, two studies have reported increased spontaneous abortions among ethylene oxide-exposed women, but few other data exist. We sent questionnaires to 7,000 dental assistants, age 18-39 years, registered in California in 1987; 4,856 responded (69%). We based our analysis on 1,320 women whose most recent pregnancy was conceived while working full-time. Thirty-two women reported exposure to ethylene oxide; unexposed dental assistants comprised the comparison group. We estimated relative risks of spontaneous abortion and preterm birth using a person-week model. We estimated relative risks of postterm birth (greater than or equal to 42 weeks) and a combined adverse outcomes model using logistic regression. Among exposed women, the age-adjusted relative risk of spontaneous abortion was 2.5 [95% confidence interval (CI) = 1.0-6.3], for preterm birth 2.7 (95% CI = 0.8-8.8), and for postterm birth 2.1 (95% CI = 0.7-5.9). The estimated relative risk of any of these adverse outcomes among exposed women was 2.5 (95% CI = 1.0-6.1) after adjusting for age, nitrous oxide, and number of mercury amalgams prepared. These data further implicate ethylene oxide as a possible reproductive toxicant in humans. RP Rowland, AS (reprint author), NIEHS,EPIDEMIOL BRANCH,A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 25 TC 39 Z9 42 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1996 VL 7 IS 4 BP 363 EP 368 DI 10.1097/00001648-199607000-00005 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UT954 UT WOS:A1996UT95400007 PM 8793361 ER PT J AU Sorlie, PD Johnson, NJ AF Sorlie, PD Johnson, NJ TI Validity of education information on the death certificate SO EPIDEMIOLOGY LA English DT Article DE death certificates; education; data collection ID INDEX; ASCERTAINMENT; RESPONDENTS AB We compared education as recorded on the death certificate with education ascertained before death from a household survey of 10,423 persons age 25 years or more who died in 1989. There was a tendency for the decedent's education to be reported at a higher level on the death certificate than at baseline. Of those who were reported as high school graduates on the death certificate, 38% reported that they had less than a high school education at baseline. The bias was more pronounced in older than younger decedents. RP Sorlie, PD (reprint author), NHLBI,ROCKLEDGE CTR 2,NIH,MAIL STOP CODE 7934,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 11 TC 55 Z9 55 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1996 VL 7 IS 4 BP 437 EP 439 DI 10.1097/00001648-199607000-00017 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UT954 UT WOS:A1996UT95400019 PM 8793373 ER PT J AU Wilcox, AJ AF Wilcox, AJ TI Benefits of ''harmful'' genes SO EPIDEMIOLOGY LA English DT Article RP Wilcox, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,MD A3-05,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 7 TC 1 Z9 1 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1996 VL 7 IS 4 BP 450 EP 451 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UT954 UT WOS:A1996UT95400023 PM 8793377 ER PT J AU Kubota, H Watanabe, Y Sato, S Fukao, K Hiraiwa, R Yamamoto, S Yagi, K Seino, M AF Kubota, H Watanabe, Y Sato, S Fukao, K Hiraiwa, R Yamamoto, S Yagi, K Seino, M TI Characteristics of epileptic syndromes in which MEG lateralized the origin of synchronous and almost symmetrical EEG spike-and-waves. SO EPILEPSIA LA English DT Article; Proceedings Paper CT 29th Congress of the Japan-Epilepsy-Society CY OCT 05-06, 1995 CL BEPPU, JAPAN SP Japan Epilepsy Soc C1 NINCDS,NIH,BETHESDA,MD 20892. RP Kubota, H (reprint author), SHIZUOKA HIGASHI HOSP,NATL EPILEPSY CTR,SHIZUOKA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 1996 VL 37 SU 3 BP 79 EP 79 DI 10.1111/j.1528-1157.1996.tb01846.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA UZ466 UT WOS:A1996UZ46600035 ER PT J AU Epstein, N Epstein, M Boulet, A Fibach, E Rodgers, GP AF Epstein, N Epstein, M Boulet, A Fibach, E Rodgers, GP TI Monoclonal antibody-based methods for quantitation of hemoglobins: Application to evaluating patients with sickle cell anemia treated with hydroxyurea SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE ELISA; fetal hemoglobin; flow cytometry; hemoglobinopathies; monoclonal antibodies ID INCREASED FETAL HEMOGLOBIN; GAMMA-GLOBIN SYNTHESIS; DISEASE PATHOPHYSIOLOGY; ERYTHROID PRECURSORS; PRENATAL-DIAGNOSIS; BETA-THALASSEMIA; MATERNAL BLOOD; F-CELLS; HB-F; 4-PHENYLBUTYRATE AB High-titer monoclonal antibodies (mAb) were raised against chromatographically purified human hemoglobin (Hb) species. These mAb were specific for either Hb A, Hb F, Hb S or Hb C. Based on these antibodies, which were directly conjugated with either fluorochromes or an enzyme (horseradish peroxidase), we developed immunoassays for determining the Hb profile in the peripheral blood; an enzyme-linked immunosorbent assay (ELISA) for determining the absolute and relative quantities of various Hb species and one-step immunolabeling for fluorescence microscopic and flow cytometric analyses of the distribution of RBC with respect to their Hb types. We utilized these methods for monitoring the Hb F level and the percentage of Hb F-containing cells in patients with sickle cell anemia undergoing treatment with hydroxyurea. C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. ISOLAB INC,AKRON,OH 44321. HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. FU NHLBI NIH HHS [R43 HL52435-01] NR 49 TC 15 Z9 15 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUL PY 1996 VL 57 IS 1 BP 17 EP 24 PG 8 WC Hematology SC Hematology GA UZ413 UT WOS:A1996UZ41300002 PM 8698126 ER PT J AU Weinberg, I Majewski, S Weisenberger, A Markowitz, A Aloj, L Majewski, L Danforth, D Mulshine, J Cowan, K Zujewski, J Chow, C Jones, E Chang, V Berg, W Frank, J AF Weinberg, I Majewski, S Weisenberger, A Markowitz, A Aloj, L Majewski, L Danforth, D Mulshine, J Cowan, K Zujewski, J Chow, C Jones, E Chang, V Berg, W Frank, J TI Preliminary results for positron emission mammography: Real-time functional breast imaging in a conventional mammography gantry SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE breast; cancer; positron; mammography; fluorine-18 2-deoxy-2-fluoro-D-glucose AB In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast: cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy. C1 NIH,BETHESDA,MD 20892. CONTINUOUS ELECTRON BEAM ACCELERATOR FACIL,NEWPORT NEWS,VA. UNIV MARYLAND,DEPT RADIOL,BALTIMORE,MD 21201. NR 2 TC 63 Z9 66 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD JUL PY 1996 VL 23 IS 7 BP 804 EP 806 DI 10.1007/BF00843710 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UX172 UT WOS:A1996UX17200011 PM 8662120 ER PT J AU Friedman, EG Koch, R Azen, C Levy, H Hanley, W Matalon, R Rouse, B Trefz, F delaCruz, F AF Friedman, EG Koch, R Azen, C Levy, H Hanley, W Matalon, R Rouse, B Trefz, F delaCruz, F TI The International Collaborative Study on maternal phenylketonuria: Organization, study design and description of the sample SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE maternal phenylketonuria; indices of dietary control; phenylalanine; pregnancy; microcephaly AB The International Maternal Phenylketonuria (PKU) Collaborative Study commenced in 1984 to evaluate the efficacy of the low-phenylalanine diet in reducing the morbidity associated with maternal PKU syndrome. Four hundred and sixty eight (468) pregnancies resulted in 331 live births, 3 stillbirths, 61 spontaneous abortions, 2 ectopic pregnancies and 71 elective terminations. Since its inception, the study has steadily progressed toward its goal of diet initiation preconception or early in pregnancy. By 1994, 51% of the sample began the diet preconceptionally, with an additional 41% doing so by 8 weeks gestation. The number of adolescent pregnancies has decreased from 31% to 9%, college attendance has increased from 5% to 16%, number of women in the lowest socioeconomic classes has decreased from 95% to 59% and average IQ has increased from 78 to 88, The organization of the network of 130 referral centers and clinics within the U.S.A., Canada and Germany and the objectives of the scientific research investigation have served to provide a derived benefit of outreach, education, reproductive counseling and early diet intervention in a large cohort of PKU women. C1 CHILDRENS HOSP,DIV MED GENET,LOS ANGELES,CA 90027. UNIV SO CALIF,DEPT PEDIAT,LOS ANGELES,CA 90089. BOSTON CHILDRENS HOSP,BOSTON,MA. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. MIAMI CHILDRENS HOSP,RES INST,MIAMI,FL. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. UNIV TUBINGEN,TUBINGEN,GERMANY. NICHHD,BETHESDA,MD 20892. RP Friedman, EG (reprint author), CHILDRENS HOSP,PKU PROGRAM 73,4650 SUNSET BLVD,LOS ANGELES,CA 90027, USA. FU NICHD NIH HHS [N01-HD-2-3148] NR 9 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JUL PY 1996 VL 155 SU 1 BP S158 EP S161 DI 10.1007/PL00014236 PG 4 WC Pediatrics SC Pediatrics GA UW468 UT WOS:A1996UW46800039 PM 8828635 ER PT J AU Hanley, WB Koch, R Levy, HL Matalon, R Rouse, B Azen, C delaCruz, F AF Hanley, WB Koch, R Levy, HL Matalon, R Rouse, B Azen, C delaCruz, F TI The North American Maternal Phenylketonuria Collaborative Study, developmental assessment of the offspring: Preliminary report SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE phenylketonuria; Maternal phenylketonuria ID HYPERPHENYLALANINEMIA; PKU; CHILDREN AB Preliminary results of 2-year Bayley and 4-year McCarthy test scores are presented. To date numbers are too small to statistically correlate: - offspring from pregnancies in which diet was started prior to conception, offspring from pregnancies with phenylalanine (Phe) levels of 120-360 mu mol/l versus 360-600 mu mol/l, influence of home environment, influence of maternal nutrition, language development, behaviour/hyperactivity, Revised Wechsler Intelligence Score, school performance and learning disabilities. Two-year Bayley scores (mental and motor) revealed a median developmental quotient of 113 in 58 off-spring from control pregnancies, 104 in 19 offspring from untreated ''non-phenylketonuria (PKU) mild hyperphenylalaninaemia'' (natural Phe levels < 600 mu mol/l) pregnancies, 104 in 32 offspring from pregnancies whose Phe levels decreased on treatment to < 600 mu mol/l by 10 weeks gestation and remained in that range for the remainder of the pregnancy, 98 in offspring from 32 pregnancies where permanent control was not achieved until 10-20 weeks and 72 in offspring from 51 pregnancies where control was not attained until after 20 weeks gestation. IQ scores determined by the McCarthy test at age 4-5 years revealed a mean of 112 in 43 offspring of control mothers, 99 in 12 offspring of ''non PKU mild hyperphenylalaninaemia'' women, 93 in 14 offspring whose mother's Phe levels were continuously under 600 mu mol/l by 10 weeks gestation, 88 in 24 offspring from pregnancies in metabolic control by 10-20 weeks and 73 in 28 offspring of pregnancies not in metabolic control until after 20 weeks gestation. These preliminary results suggest that early and adequate dietary treatment during pregnancy in maternal PKU may provide some protection to the fetus for later intellectual development but much more data is required before definitive statements about cognition can be made. C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. NICHHD,BETHESDA,MD 20892. CHILDRENS HOSP,BOSTON,MA 02115. MIAMI CHILDRENS HOSP,MIAMI,FL. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. RP Hanley, WB (reprint author), HOSP SICK CHILDREN,DIV CLIN GENET,555 UNIV AVE,TORONTO,ON M5G 1X8,CANADA. FU NICHD NIH HHS [N01-HD-2-3148] NR 22 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JUL PY 1996 VL 155 SU 1 BP S169 EP S172 DI 10.1007/PL00014240 PG 4 WC Pediatrics SC Pediatrics GA UW468 UT WOS:A1996UW46800042 PM 8828638 ER PT J AU Koch, R Levy, H Hanley, W Matalon, R Rouse, B Trefz, F delaCruz, F AF Koch, R Levy, H Hanley, W Matalon, R Rouse, B Trefz, F delaCruz, F TI Outcome implications of the international maternal phenylketonuria collaborative study (MPKUCS): 1994 SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE phenylalanine; gestational age; pregnancy outcome; restricted phenylalanine diet; microcephaly AB It is well established that women with phenylketonuria who remain untreated during pregnancy face serious problems in offspring outcome. Surveys have documented that maternal phenylalanine (Phe) blood concentrations above 1200 mu mol/l are associated with microcephaly, congenital heart disease and intrauterine growth retardation among their offspring. To investigate the efficacy of the Phe restricted diet, the National Institute of Child Health and Human Development in Bethesda Maryland developed an international study to evaluate fetal outcome in pregnancies treated with the Phe restricted diet. The study involves over 100 metabolic clinics in the United States, Canada and Germany, and is now in its 10th year. The results included in this report are still preliminary in nature and the actual risk for such pregnancies remains to be determined. C1 UNIV SO CALIF,DEPT PEDIAT,LOS ANGELES,CA 90089. CHILDRENS HOSP,DIV GENET BIOCHEM,BOSTON,MA. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. MIAMI CHILDRENS HOSP,RES INST,MIAMI,FL. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. UNIV TUBINGEN,REUTLINGEN,GERMANY. NICHHD,BETHESDA,MD 20892. RP Koch, R (reprint author), CHILDRENS HOSP LOS ANGELES,DIV MED GENET,PKU 73,4650 SUNSET BLVD,LOS ANGELES,CA 90027, USA. FU NICHD NIH HHS [N01-HD-2-3148] NR 5 TC 11 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JUL PY 1996 VL 155 SU 1 BP S162 EP S164 DI 10.1007/PL00014238 PG 3 WC Pediatrics SC Pediatrics GA UW468 UT WOS:A1996UW46800040 PM 8828636 ER PT J AU Levy, HL Waisbren, SE Lobbregt, D Allred, E Leviton, A Koch, R Hanley, WB Rouse, B Matalon, R delaCruz, F AF Levy, HL Waisbren, SE Lobbregt, D Allred, E Leviton, A Koch, R Hanley, WB Rouse, B Matalon, R delaCruz, F TI Maternal non-phenylketonuric mild hyperphenylalaninemia SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE maternal mild hyperphenylalaninemia; phenylketonuria; birth weight, length; birth head circumference; IQ ID INTERNATIONAL SURVEY; FETUS AB Unlike maternal phenylketonuria (PKU) which produces severe birth defects when untreated during pregancy, maternal non-PKU mild hyperphenylalaninemia (MHP) has a less severe impact but whether it is benign or may have long-term consequences for offspring has been unclear. From an international survey of maternal MHP we obtained information about 86 mothers (blood phenylalanine (Phe) 150-720 mu mol/l). their 219 untreated pregnancies and 173 offspring, Spontaneous fetal loss and congenital anomalies were no more frequent than normally expected. Median Z-scores for birth length and birth head circumference and offspring IQ (100), however, were significantly lower for maternal Phe > 400 mu mol/l than for maternal Phe < 400 mu mol/l, in which the median offspring IQ was 108. Data on maternal MHP from the prospective Maternal PKU Collaborative Study (MPKUCS) are as yet incomplete but seem to be conforming to the general pattern of the international survey. We conclude that maternal blood Phe levels above 400 mu mol/l in maternal MHP are associated with lower birth measurements and slightly lower offspring IQ. It would seem that dietary intervention to lower the maternal Phe levels to below 400 mu mol/l might be indicated in maternal MHP pregnancies with the higher blood Phe levels. C1 HARVARD UNIV,SCH MED,BOSTON,MA. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. UNIV TEXAS,GALVESTON,TX. CHILDRENS HOSP,MIAMI,FL. NICHHD,NIH,BETHESDA,MD 20892. RP Levy, HL (reprint author), CHILDRENS HOSP,IC SMITH 106,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NICHD NIH HHS [N01-HD-2-3149] NR 16 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JUL PY 1996 VL 155 SU 1 BP S20 EP S25 DI 10.1007/PL00014243 PG 6 WC Pediatrics SC Pediatrics GA UW468 UT WOS:A1996UW46800007 PM 8828603 ER PT J AU Russell, P Qin, C Garland, D Tabor, Y Zigler, JS AF Russell, P Qin, C Garland, D Tabor, Y Zigler, JS TI RNA and protein synthesis in the primate lens SO EXPERIMENTAL EYE RESEARCH LA English DT Letter RP Russell, P (reprint author), NEI,NIH,LAB MECHANISMS OCULAR DIS,6 CTR DR,MSC 2735,BLDG 6,RM 228,BETHESDA,MD 20892, USA. NR 9 TC 5 Z9 5 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 JUL PY 1996 VL 63 IS 1 BP 121 EP 123 DI 10.1006/exer.1996.0099 PG 3 WC Ophthalmology SC Ophthalmology GA VB650 UT WOS:A1996VB65000015 PM 8983958 ER PT J AU Rosenberg, HF Dyer, KD Li, F AF Rosenberg, HF Dyer, KD Li, F TI Characterization of eosinophils generated in vitro from CD34(+) peripheral blood progenitor cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE eosinophils; hematopoiesis; CD34 ID CHRONIC GRANULOMATOUS-DISEASE; MEDIATED GENE-TRANSFER; LEUKEMIA HL-60 CELLS; CATIONIC PROTEIN; STEM-CELLS; HEMATOPOIETIC PROGENITORS; LINE; INTERLEUKIN-5; DIFFERENTIATION; PROMOTER AB Methods for isolation and cultivation of CD34(+) peripheral blood progenitor cells (PBPCs) have facilitated their use in autologous transplantation and as potential targets for gene therapy. In this work, we present the possibility of using these isolated cells to study lineage-specific hematopoietic differentiation. We have shown that differentiating PBPCs faithfully replicate transcriptional events that occur during maturation of the eosinophil lineage; messenger RNAs encoding the five eosinophil granule proteins were detected by reverse-transcriptiontase polymerase chain reaction (RT-PCR) after 2-3 days of cytokine-stimulated growth. Only three of the five proteins were detected by immunofluorescence staining after 14 days of cytokine-stimulated growth; the percentage of Charcot-Leyden crystal protein (CLC)-containing cells (16-18%) exceeded that of eosinophil peroxidase (EPO)-containing cells (7-8%), which in turn exceeded that of eosinophil-derived neurotoxin (EDN)-containing cells (2-4%). While the electrophoretic mobilities of both CLC and EPO synthesized by differentiating PBPCs were similar to those of their normal counterparts, immunoreactive EDN was found to be heterogeneous and of higher molecular weight than EDN found in mature eosinophils. It is not clear whether our results, which show progressive, but incomplete, differentiation of PBPCs into eosinophils, reflect a lack of knowledge as to what factors are essential for complete differentiation in vitro or relate to the inherent capacity of PBPCs to differentiate along this lineage. RP Rosenberg, HF (reprint author), NIAID,HOST DEF LAB,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 11N104,BETHESDA,MD 20892, USA. NR 51 TC 12 Z9 12 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1996 VL 24 IS 8 BP 888 EP 893 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA UY210 UT WOS:A1996UY21000006 PM 8690047 ER PT J AU Lamb, ME AF Lamb, ME TI Family, justice, and delinquency - Geiger,B, Fischer,M SO FAMILY RELATIONS LA English DT Book Review RP Lamb, ME (reprint author), NICHHD,SECT SOCIAL & EMOT DEV,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNC FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0197-6664 J9 FAM RELAT JI Fam. Relat. PD JUL PY 1996 VL 45 IS 3 BP 355 EP 355 DI 10.2307/585516 PG 1 WC Family Studies; Social Work SC Family Studies; Social Work GA VB874 UT WOS:A1996VB87400021 ER PT J AU Horn, V Minucci, S Ogryzko, VV Adamson, ED Howard, BH Levin, AA Ozato, K AF Horn, V Minucci, S Ogryzko, VV Adamson, ED Howard, BH Levin, AA Ozato, K TI RAR and RXR selective ligands cooperatively induce apoptosis and neuronal differentiation in P19 embryonal carcinoma cells SO FASEB JOURNAL LA English DT Article DE retinoids; RAR; RXR ID RETINOIC ACID; RECEPTOR; IDENTIFICATION AB Retinoids cause differentiation in embryonal carcinoma (EC) cells, thus mimicking events in mammalian development, Here, we show that retinoids also cause apoptosis in P19 EC cells, Characteristic DNA fragmentation was observed within 36 h after addition of retinoic acid (RA), Synthetic retinoids that are selective for RA receptors (RAR) were also effective in inducing apoptosis, whereas RXR selective ligands were without effect, The combination of RAR and RXR ligands resulted in a synergistic increase in apoptotic cell death, As with apoptosis, neuronal differentiation of P19 cells was synergistically induced by the combination of RAR and RXR ligands. Data obtained with an RAR antagonist and with P19 cells carrying a dominant negative RXR indicate that the two processes are receptor mediated, Together, our results indicate that retinoid-induced apoptosis and neuronal differentiation are closely coupled, and that both RAR and RXR play a role in these processes as active receptors for their respective ligands. C1 NICHHD,LAB MOLEC GROWTH REGULAT,NIH,BETHESDA,MD 20892. LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. ISIS PHARMACEUT,CARLSBAD,CA 92008. RI Minucci, Saverio/J-9669-2012; Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 26 TC 64 Z9 66 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 JUL PY 1996 VL 10 IS 9 BP 1071 EP 1077 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UY932 UT WOS:A1996UY93200018 PM 8801169 ER PT J AU Simpson, JL Carson, SA Mills, JL Conley, MR Aarons, J Holmes, LB JovanovicPeterson, L Knopp, R Metzger, B AF Simpson, JL Carson, SA Mills, JL Conley, MR Aarons, J Holmes, LB JovanovicPeterson, L Knopp, R Metzger, B TI Prospective study showing that antisperm antibodies are not associated with pregnancy losses SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT Canadian-Fertility-and-Andrology-Society Meeting CY SEP 20-23, 1995 CL MONTEBELLO, CANADA SP Canadian Fertil & Androl Soc DE pregnancy loss; first trimester; antisperm antibodies; prospective ID INVITRO FERTILIZATION; SPONTANEOUS-ABORTION; AGGLUTINATION-TEST; SPERM ANTIBODIES; WOMEN AB Objective: To obtain prospective data on the relationship between presence of antisperm antibodies in maternal sera and first trimester pregnancy losses. Design: First trimester sera obtained from diabetic and nondiabetic women recruited within 21 days of conception mere analyzed using the indirect immunobead test for immunoglobulin (Ig) G, IgA, and IgM antisperm antibodies. Regional binding also was considered: sperm head, midpiece, and sperm tail. Results were correlated with pregnancy outcome. Setting: Five university centers. Patients: One hundred eleven women who experienced pregnancy loss (55 diabetic; 56 nondiabetic) were matched 2:1 with 104 diabetic and 116 nondiabetic women (controls) who subsequently had a normal Liveborn infant. Intervention: None. Main Outcome Measure: Pregnancy outcome (spontaneous abortion, Liveborn) correlated with presence or absence of antisperm antibodies. Results: Analyzing samples without knowledge of clinical status, no differences were observed with respect to IgG, IgA, and IgM binding when a positive test was defined as 50% of sperm showing antibody binding. Likewise, no association was found for IgG and IgM antisperm antibodies at 20% binding. The only positive finding was observed for IgA antisperm antibodies at 20% binding (Fisher's Exact test). This one positive finding merely could reflect multiple comparisons. No significant differences between groups were observed when analysis was stratified according to location of antibody binding (head, midpiece, tail tip, entire sperm), When the sample was stratified into those having and not having a prior loss, a relationship between antisperm antibodies and pregnancy loss still was not evident. Conclusion: Further work is necessary to determine whether IgA antisperm antibodies truly are associated with pregnancy loss or whether antisperm antibodies play any role in repetitive aborters. Findings in this study suggest that antisperm antibodies do not play a major role in pregnancy loss. C1 UNIV TENNESSEE,MEMPHIS,TN. NIH,BETHESDA,MD 20892. MAGEE WOMENS HOSP,PITTSBURGH,PA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. SANSUM MED RES FDN,SANTA BARBARA,CA 93105. UNIV WASHINGTON,SEATTLE,WA 98195. NORTHWESTERN UNIV,CHICAGO,IL 60611. RP Simpson, JL (reprint author), BAYLOR COLL MED,DEPT OBSTET & GYNECOL,6550 FANNIN,SUITE 701,HOUSTON,TX 77030, USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1996 VL 66 IS 1 BP 36 EP 42 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA UT304 UT WOS:A1996UT30400007 PM 8752608 ER PT J AU Stojilkovic, SS Catt, KJ AF Stojilkovic, SS Catt, KJ TI Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review ID PROTEIN-KINASE-C; VASCULAR SMOOTH-MUSCLE; GONADOTROPIN-RELEASING-HORMONE; ATRIAL-NATRIURETIC-PEPTIDE; ANTERIOR-PITUITARY-CELLS; MESSENGER-RIBONUCLEIC-ACID; PHOSPHOLIPASE-D ACTIVATION; ADRENAL GLOMERULOSA CELLS; THYROID FOLLICULAR CELLS; OVARIAN GRANULOSA-CELLS AB Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of Fm and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive Em are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ET(A) and ET(B) receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ET(A) receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca2+-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+](i) that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca2+-mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D- and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that Em participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells. (C) 1996 Academic Press, Inc. RP Stojilkovic, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,ROOM 6A-36,49 CONVENT DR,MSC 4510,BETHESDA,MD 20892, USA. NR 224 TC 61 Z9 62 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 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JUL PY 1996 VL 17 IS 3 BP 327 EP 369 DI 10.1006/frne.1996.0009 PG 43 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UV596 UT WOS:A1996UV59600003 PM 8812299 ER PT J AU Rao, GN AF Rao, GN TI New diet (NTP-2000) for rats in the national toxicology program toxicity and carcinogenicity studies SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID BODY-WEIGHT; FAT; MICE AB Composition of diet may influence growth, diseases, tumor rates, and responses to chemical treatment. Since 1980 the NIH-07 open formula nonpurified diet has been the selected diet for the National Toxicology Program (NTP) toxicity and carcinogenicity studies in rodents. Studies with nonpurified experimental diets with lower protein and higher fat and fiber than the NIH-07 diet indicated that the diet for Fischer-344 (F344) rats in long-term studies could be modified to decrease the severity of chronic diseases and to decrease/delay the development of spontaneous tumors. Based on the results of these studies a new open formula nonpurified diet designated as NTP-2000 was formulated to contain similar to 14.5% protein, similar to 8.5% fat, and similar to 9.5% fiber. Corn, wheat, and wheat middlings contribute to about 60% of the ingredients; soybean meal, fish meal, and alfalfa meal are the additional sources of protein; purified cellulose, oat hulls, and alfalfa meal are the major sources of fiber; and soy oil and corn oil are the major sources of fat in the NTP-2000 diet. The Ca:P ratio and mineral and vitamin concentrations were reformulated based on AIN-93 and NRC-95 recommendations. The NIH-07 and the NTP-2000 diets were fed to groups of 6-week-old F344 rats for 13 weeks and evaluated for growth patterns, food and water consumptions, hematology and clinical chemistry parameters, and organ weights and pathological changes. Growth patterns and body weights were similar for both diets. Food consumptions were slightly higher and water consumptions were slightly lower for the groups fed NTP-2000 diet. There were no differences in hematological parameters between the groups fed the above diets. Serum levels of cholesterol, alkaline phosphatase, and 5' nucleotidase were slightly higher in groups fed the NTP-2000 diet possibly due to higher fat content of this diet. However, the serum triglyceride levels were slightly lower in groups fed the NTP-2000 diet and it may be related to higher fiber content of the NTP-2000 diet. The liver and kidney weights of the groups fed NTP-2000 diet were significantly lower possibly due to lower protein content of this diet and lower protein consumption associated changes in Phase I and Phase II drug metabolizing enzyme systems. The adrenal weights were also lower in groups fed the new diet. The NTP-2000 diet prevented nephrocalcinosis and decreased the severity of nephropathy and cardiomyopathy, the common lesions of F344 rats in 13-week studies. These results indicate that the NTP-2000 diet is adequate for growth and maintenance of rats and appears to prevent or decrease the severity of diet-associated lesions. RP Rao, GN (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 52 Z9 52 U1 2 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 JUL PY 1996 VL 32 IS 1 BP 102 EP 108 DI 10.1006/faat.1996.0112 PG 7 WC Toxicology SC Toxicology GA UW753 UT WOS:A1996UW75300013 PM 8812243 ER PT J AU Fleischer, DE Wang, GQ Dawsey, S Tio, TL Newsome, J Kidwell, J Prifti, S AF Fleischer, DE Wang, GQ Dawsey, S Tio, TL Newsome, J Kidwell, J Prifti, S TI Tissue band ligation followed by snare resection (band and snare): A new technique for tissue acquisition in the esophagus SO GASTROINTESTINAL ENDOSCOPY LA English DT Article C1 GEORGETOWN UNIV,MED CTR,DIV GASTROENTEROL,RES RESOURCE FACIL,WASHINGTON,DC 20007. CHINESE ACAD MED SCI,CANC HOSP,BEIJING,PEOPLES R CHINA. NATL CANC INST,BETHESDA,MD. NR 9 TC 57 Z9 59 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 1996 VL 44 IS 1 BP 68 EP 72 DI 10.1016/S0016-5107(96)70233-X PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VB051 UT WOS:A1996VB05100013 PM 8836721 ER PT J AU Cormack, BP Valdivia, RH Falkow, S AF Cormack, BP Valdivia, RH Falkow, S TI FACS-optimized mutants of the green fluorescent protein (GFP) SO GENE LA English DT Article; Proceedings Paper CT Conference on Fluorescent Proteins and Applications CY MAR 06-07, 1995 CL PALO ALTO, CA SP Palo Alto Inst Molec Med DE GFP mutation; FITC; fluorescence-activated cell sorter; fluorescence intensity ID CODON AB We have constructed a library in Escherichia coli of mutant gfp genes (encoding green fluorescent protein, GFP) expressed from a tightly regulated inducible promoter. We introduced random amino acid (aa) substitutions in the twenty aa flanking the chromophore Ser-Tyr-Gly sequence at aa 65-67. We then used fluorescence-activated cell sorting (FAGS) to select variants of GFP that fluoresce between 20- and 35-fold more intensely than wild type (wt), when excited at 488 nm. Sequence analysis reveals three classes of aa substitutions in GFP. All three classes of mutant proteins have highly shifted excitation maxima, In addition, when produced in E. coli, the folding of the mutant proteins is more efficient than folding of wt GFP. These two properties contribute to a greatly increased (100-fold) fluorescence intensity, making the mutants useful for a number of applications. C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RP Cormack, BP (reprint author), STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,FAIRCHILD D035,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI 36396] NR 10 TC 2054 Z9 2169 U1 22 U2 255 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 1 PY 1996 VL 173 IS 1 BP 33 EP 38 DI 10.1016/0378-1119(95)00685-0 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA UY073 UT WOS:A1996UY07300006 PM 8707053 ER PT J AU Valdivia, RH Hromockyj, AE Monack, D Ramakrishnan, L Falkow, S AF Valdivia, RH Hromockyj, AE Monack, D Ramakrishnan, L Falkow, S TI Applications for green fluorescent protein (GFP) in the study of host-pathogen interactions SO GENE LA English DT Article; Proceedings Paper CT Conference on Fluorescent Proteins and Applications CY MAR 06-07, 1995 CL PALO ALTO, CA SP Palo Alto Inst Molec Med DE Salmonella; Yersinia; Mycobacteria; flow cytometry; histology; gfp expression vectors; fluorescence microscopy ID CELLS; EXPRESSION; YERSINIAE; GENE AB The green fluorescent protein (GFP) from Aequorea victor ia is a novel fluorescent marker that has potential use in the study of bacterial pathogenicity, To explore some of the potential applications of GFP to the study of host-parasite interactions, we constructed two GFP expression vectors suitable for different facultative intracellular bacterial pathogens, The first expression vector was tested in the enteric pathogens, Salmonella typhimurium and Yersinia pseudotuberculosis, and the second vector tested in Mycobacterium marinum (Mm). Both expression vectors were found to be stable and to direct high levels of GFP synthesis. Standard epifluorescence microscopy was used to detect all three bacterial pathogenic species during the early and late stages of infection of live mammalian cells, Mm expressing gfp was also visualized in infected animal tissues, gfp expression did not adversely affect bacterial survival, nor did it compromise entry into mammalian cells or their survival within macrophages. In addition, all three gfp-expressing bacterial pathogens could be detected and sorted in a flow cytometer, either alone or in association with epithelial cells or macrophages. Therefore, GFP not only provides a convenient tool to image pathogenic bacteria, but allows the quantitative measurement of bacterial association with mammalian cells. C1 NIAID, ROCKY MT LABS, HAMILTON, MT 59840 USA. RP STANFORD UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, STANFORD, CA 94305 USA. FU NIAID NIH HHS [AI36396] NR 24 TC 193 Z9 205 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD JUL 1 PY 1996 VL 173 IS 1 BP 47 EP 52 DI 10.1016/0378-1119(95)00706-7 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA UY073 UT WOS:A1996UY07300008 PM 8707055 ER PT J AU Cunha, V Gutierrez, J Correa, FMA AF Cunha, V Gutierrez, J Correa, FMA TI Biologic activities of iodinated analogues of Tyr(0)-bradykinin and bradykinin-Ile(10)-Tyr(11) assessed in the rat uterus and the guinea pig ileum SO GENERAL PHARMACOLOGY LA English DT Article DE kinins; bradykinin; bradykinin receptor; rat uterus; guinea pig ileum; phyllokinin ID BRADYKININ RECEPTOR; BINDING AB 1. The biological activity of bradykinin (BK) and analogues containing Tyr in extended N- or C-terminal portions of the molecule, as well as that of their iodinated products, was compared in isolated rat uterus and guinea pig ileum preparations. 2. BK-Tyr(10) and BK-Ile(10)-Tyr(11) were obtained by solid phase synthesis employing fmoc chemistry. 3. Iodination of BK-Ile(10)-Tyr(11) and Tyr(0)-BK was performed using iodobeads(R), and the products were purified by reverse-phase HPLC. 4. The relative potency (RP) of noniodinated analogues in the uterus was: Tyr(0)-BK (13)=BK (1.O)>BK-Ile(10)-Tyr(11) (0.45)>>BK-Tyr(10) (0.02) and BK (1.O)>BK-ILe(10) -Tyr(11) (0.25)=Tyr(0)-BK (0.22)>>>BK-Tyr(10) (0.002). The RP of mono-iodo (MT) and di-iodo (DI) products was: BK (1.O)>DI-BK-Ile(10)-Tyr(11) (0.63)=DI-Tyr(0)-BK (0.63)>MI-Tyr(0)-BK (0.46)=MI-BK-Ile(10)-Tyr(11) (0.40). 5. The RP of noniodinated analogues in the guinea pig ileum was: BK (1.O)>ML-Tyr(0)-BK (0.39)>MI-BK-Ile(10)-Tyr(11) (0.17)=DI-Tyr(0)-BK (0.16)=DI-BK-Ile(10)-Tyr(11) (0.13). 6. Differences in RP of 8-10 fold for Tyr(0)-BK or BK-Tyr(10) and 2-fold for BK-Ile(10)-Tyr(11) were observed between the two preparations used, indicating possible receptor differences. 7. Iodination caused a reduction in the RP of the analogues in both preparations. 8. In the rat uterus, the changes in the RP of the Tyr(0)-BK analogues were more evident than those observed with the iodinated analogues of BK-Ile(10)-Tyr(11), indicating that iodination causes different changes in RP, according to the localization of the Tyr in the molecule. 9. The data support the idea that iodinated analogues of BK-Ile(10)-Tyr(11), with intact N-terminal portion, may be as useful as iodinated analogues of Tyr-(0)-BK for the study of BK receptors. C1 UNIV SAO PAULO,SCH MED RIBEIRAO PRETO,DEPT PHARMACOL,BR-14049900 RIBEIRAO PRET,SP,BRAZIL. NIMH,LAB CELLULAR BIOL,BETHESDA,MD 20892. RI Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 19 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-3623 J9 GEN PHARMACOL JI Gen. Pharmacol. PD JUL PY 1996 VL 27 IS 5 BP 787 EP 794 DI 10.1016/0306-3623(95)02104-3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VB136 UT WOS:A1996VB13600007 PM 8842680 ER PT J AU Heinemann, JA Scott, HE Williams, M AF Heinemann, JA Scott, HE Williams, M TI Doing the conjugative two-step: Evidence of recipient autonomy in retrotransfer SO GENETICS LA English DT Article ID HOST-RANGE; BACTERIAL CONJUGATION; CHROMOSOMAL MARKERS; GENE-TRANSFER; PLASMID RK2; REPLICATION; DERIVATIVES; OPERON; REGION AB Bidirectional exchange of genetic information, called retrotransfer, during bouts of bacterial conjugation has drawn the interest of those concerned with the risk of releasing genetically engineered microbes, the fluidity of genes among species, and the mechanism of DNA transport between cells. The phenomenon has generated two models in explanation, both of which yield highly testable predictions. The first model, called the one-step, predicts that the flow of genes from recipient bacteria to donor bacteria is mechanistically distinct from, but dependent on, conjugation between donors and recipients. The second model, called the two-step, predicts that the same genetic requirements and mechanistic constraints apply to the process of gene flow from recipients to donors as for gene flow from donors to recipients. The requirement for expression of at least 10 plasmid-encoded genes in recipients, sensitivity of the reverse flow (recipient to donor) to restriction of DNA transferring from the donor, and the requirement of an additional 30-90 min for DNA to flow from recipients back to donors are predictions of the two-step model and directly refute the one-step model. Retrotransfer of genes to donors during conjugation remains genetically and physically indistinguishable from two successive rounds of conjugation between neighbors. C1 NIAID,MICROBIAL STRUCT & FUNCT LAB,NIH,ROCKY MT LABS,HAMILTON,MT 59840. RP Heinemann, JA (reprint author), UNIV CANTERBURY,DEPT PLANT & MICROBIAL SCI,PRIVATE BAG 4800,CHRISTCHURCH 1,NEW ZEALAND. NR 36 TC 16 Z9 16 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 1996 VL 143 IS 3 BP 1425 EP 1435 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA UU742 UT WOS:A1996UU74200034 PM 8807313 ER PT J AU Prochazka, M AF Prochazka, M TI Microsatellite hybrid capture technique for simultaneous isolation of various STR markers SO GENOME RESEARCH LA English DT Article ID HYBRIDIZATION SELECTION; REPEAT SEQUENCES; PIMA-INDIANS; RAPID METHOD; CLONES; CONSTRUCTION; CHROMOSOMES AB The microsatellite hybrid capture technique was designed to enrich simultaneously for various microsatellite repeats from a genomic done. It is illustrated in this report that different repeat motifs, including polymorphic ones, can be efficiently isolated in a single experiment. in principle, this technique can be applied to any type of genomic clones to facilitate the isolation of informative markers for fine mapping of subchromosomal regions of interest, and for linkage and association studies of candidate genes for which no polymorphic markers are available yet. RP Prochazka, M (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 21 TC 19 Z9 20 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUL PY 1996 VL 6 IS 7 BP 646 EP 649 DI 10.1101/gr.6.7.646 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UX136 UT WOS:A1996UX13600010 PM 8796353 ER PT J AU Polymeropoulos, MH Ide, SE Wright, M Goodship, J Weissenbach, J Pyeritz, RE DaSilva, EO DeLuna, RIO Francomano, CA AF Polymeropoulos, MH Ide, SE Wright, M Goodship, J Weissenbach, J Pyeritz, RE DaSilva, EO DeLuna, RIO Francomano, CA TI The gene for the Ellis van Creveld syndrome is located on chromosome 4p16 SO GENOMICS LA English DT Article ID WOLF-HIRSCHHORN SYNDROME; HOMEOBOX GENE AB Ellis-van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by disproportionate dwarfism, polydactyly, and congenital heart disease. This rare disorder is found with increased frequency among the Old Order Amish community in Lancaster County, Pennsylvania. We have used linkage analysis to localize the gene responsible for the EVC phenotype in nine interrelated Amish pedigrees and three unrelated families from Mexico, Ecuador, and Brazil, We now report the linkage for the Ellis-van Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Z(max) = 6.91 at theta = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype. (C) 1996 Academic Press, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21218. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,GENE MAPPING UNIT,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. ALLEGHENY SINGER RES INST,PITTSBURGH,PA 15212. UNIV NEWCASTLE UPON TYNE,DEPT HUMAN GENET,NEWCASTLE TYNE NE1 7RU,TYNE & WEAR,ENGLAND. IMIP,SERV GENET MED,RECIFE,PE,BRAZIL. GENETHON,EVRY,FRANCE. RI Pyeritz, Reed/A-1364-2010 FU FDA HHS [FDR 692]; NHGRI NIH HHS [P01 HG00373]; NHLBI NIH HHS [HL 35877] NR 17 TC 65 Z9 65 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1996 VL 35 IS 1 BP 1 EP 5 DI 10.1006/geno.1996.0315 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UV869 UT WOS:A1996UV86900001 PM 8661097 ER PT J AU Antonson, P Stellan, B Yamanaka, R Xanthopoulos, KG AF Antonson, P Stellan, B Yamanaka, R Xanthopoulos, KG TI A novel human CCAAT/enhancer binding protein gene, C/EBP epsilon, is expressed in cells of lymphoid and myeloid lineages and is localized on chromosome 14q11.2 close to the T-cell receptor alpha/delta locus SO GENOMICS LA English DT Article ID LEUCINE ZIPPER PROTEINS; HUMAN CATHEPSIN-G; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; SERINE PROTEASE; NUCLEAR-PROTEIN; MAST-CELL; FAMILY; REGION AB Members of the C/EBP family of transcriptional factors have been implicated in the regulation of genes in a variety of tissues. We report here the isolation and characterization of the human C/EBP epsilon gene (CEBPE). By using low-stringency hybridization conditions and probes derived from the C/EBP alpha and C/EBP delta genes, we have isolated overlapping genomic clones that cover almost 25 kb of the C/EBP epsilon gene locus and corresponding cDNA clones. DNA sequence analysis reveals that the gene encodes a protein highly homologous to rat CRP1. The gene was assigned to chromosome 14q11.2 by fluorescence in situ hybridization and was physically Linked to the genetic marker D14S990. Based on linkage data derived from this marker, we positioned the CEBPE gene between the T-cell receptor alpha/delta locus and a cluster of four serine proteases expressed exclusively in hematopoietic cells. Expression of C/EBP epsilon was detected in Jurkat T-cell and in HL 60 promyelocytic cell lines. From a variety of normal human tissues studied, expression of mRNA was monitored only in peripheral blood mononuclear cells, tissues involved in the immune system, and ovaries. These data demonstrate that the C/EBP epsilon gene shows a restricted pattern of expression, has an intriguing chromosomal location, and suggest a possible role for the regulation of certain genes in cells of myeloid and lymphoid lineages. (C) 1996 Academic Press, Inc. C1 KAROLINSKA INST,NOVUM,DEPT BIOSCI,S-14157 HUDDINGE,SWEDEN. KAROLINSKA INST,NOVUM,DEPT MED,S-14157 HUDDINGE,SWEDEN. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 53 TC 86 Z9 88 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1996 VL 35 IS 1 BP 30 EP 38 DI 10.1006/geno.1996.0319 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UV869 UT WOS:A1996UV86900005 PM 8661101 ER PT J AU Pecker, I Avraham, KB Gilbert, DJ Savitsky, K Rotman, G Harnik, R Fukao, T Schrock, E Hirotsune, S Tagle, DA Collins, FS WynshawBoris, A Ried, T Copeland, NG Jenkins, NA Shiloh, Y Ziv, Y AF Pecker, I Avraham, KB Gilbert, DJ Savitsky, K Rotman, G Harnik, R Fukao, T Schrock, E Hirotsune, S Tagle, DA Collins, FS WynshawBoris, A Ried, T Copeland, NG Jenkins, NA Shiloh, Y Ziv, Y TI Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene SO GENOMICS LA English DT Article ID LINKAGE MAP; INSITU HYBRIDIZATION; DNA; FLUORESCENCE; LOCI AB Atm, the mouse homolog of the human ATM gene defective in ataxia-telangiectasia (A-T), has been identified, The entire coding sequence of the Atm transcript was cloned and found to contain an open reading frame encoding a protein of 3066 amino acids with 84% overall identity and 91% similarity to the human ATM protein, Variable levels of expression of Atm were observed in different tissues. Fluorescence in situ hybridization and linkage analysis located the Atm gene on mouse chromosome 9, band 9C, in a region homologous to the ATM region on human chromosome 11q22-q23. (C) 1996 Academic Press, Inc. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 RAMAT AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. GIFU UNIV,SCH MED,DEPT PEDIAT,GIFU 500,JAPAN. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. FU NIGMS NIH HHS [5F32GM15909-02] NR 32 TC 41 Z9 42 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 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1996 VL 35 IS 1 BP 39 EP 45 DI 10.1006/geno.1996.0320 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UV869 UT WOS:A1996UV86900006 PM 8661102 ER PT J AU Hoofnagle, JH Lombardero, M Zetterman, RK Lake, J Porayko, M Everhart, J Belle, SH Detre, KM AF Hoofnagle, JH Lombardero, M Zetterman, RK Lake, J Porayko, M Everhart, J Belle, SH Detre, KM TI Donor age and outcome of liver transplantation SO HEPATOLOGY LA English DT Article ID MARGINAL DONORS; ELIMINATION; MEGX AB To evaluate the effect of donor age on graft and patient outcome after liver transplantation an analysis of a large-scale cohort study was performed at three tertiary referral liver transplant centers. Between April 1990 and June 1994, 772 adults underwent an initial single-organ liver transplantion. The age of the donors averaged 35 years; 193 (25%) were 50 or above, the age used to define ''older'' donors. Groups were compared for demographic, clinical, and biochemical features. Outcome was measured using results of biochemical tests after transplantation and by graft and patient survival. Compared with younger donors, older donors were more commonly women (59% vs. 33%: P less than or equal to .001) and died of central nervous system causes (79% vs. 28%) as opposed to trauma (13% vs, 63%: P less than or equal to .001). The recipients of the two groups of donor livers did not differ in important respects, However, intraoperatively, livers from older donors were more likely to be assessed as either ''poor'' or ''fair'' as opposed to ''good'' (17% vs, 4%: P less than or equal to .001) by the harvesting surgeon and to have initial ''poor'' or ''fair'' bile production (29% vs. 18%: P less than or equal to .001). During the first week postoperatively, the serum aminotransferase and bilirubin levels and prothrombin times were higher in recipients of older than those of younger donor livers, During followup, graft survival was less for recipients of older donor livers at 3 months (81% vs, 91%: P = .0001) and at 1 (76% vs. 85%: P = .007) and 2 years (71% vs, 80%: P = .005); patient survival showed similar though less marked differences, This association of donor age and poorer graft survival persisted after adjusting for many variables using bivariate and multivariate analyses, Importantly, however, the association with poor graft survival was largely among recipients of older donor Livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers assessed as good had a retransplant-free survival similar to that of younger donor livers (87% vs, 91% at 3 months). Thus, use of older donor livers, the quality of which are judged to be good by the harvesting surgeon, is not associated with a decrease in patient or graft survival after liver transplantation. C1 NIDDKD,DIV DIGEST DIS & NUTR,NIH,BETHESDA,MD. UNIV NEBRASKA,MED CTR,OMAHA,NE. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP Hoofnagle, JH (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,127 PARRAN HALL,130 DESOTO ST,PITTSBURGH,PA 15261, USA. FU NIDDK NIH HHS [N01-DK-0-2251, N01-DK-0-2252, N01-DK-0-2253] NR 28 TC 116 Z9 121 U1 1 U2 5 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 JUL PY 1996 VL 24 IS 1 BP 89 EP 96 DI 10.1002/hep.510240116 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UW635 UT WOS:A1996UW63500016 PM 8707288 ER PT J AU Preisegger, KH Stumptner, C Riegelnegg, D Brown, PC Silverman, JA Thorgeirsson, SS Denk, H AF Preisegger, KH Stumptner, C Riegelnegg, D Brown, PC Silverman, JA Thorgeirsson, SS Denk, H TI Experimental mallory body formation is accompanied by modulation of the expression of multidrug-resistance genes and their products SO HEPATOLOGY LA English DT Article ID P-GLYCOPROTEIN GENE; INTERMEDIATE FILAMENT CYTOSKELETON; HEPATOCELLULAR CARCINOMAS; RAT-LIVER; MONOCLONAL-ANTIBODIES; HOMOZYGOUS DISRUPTION; MDR2 GENE; BODIES; MOUSE; MICE AB Mallory bodies (MBs) are characteristic morphological features of alcoholic hepatitis and are also found in other chronic liver disorders and hepatocellular neoplasms, MBs can be produced in mouse liver by chronic administration of the porphyrinogenic drugs griseofulvin (GF) and 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC). The mechanisms causing the formation of MBs are poorly understood, and the significance of MB formation during the course of liver disease remains unclear, We investigated the relationship between the mechanisms underlying the formation of MBs and the regulation of multidrug resistance (mdr) genes and their products, the P-glycoproteins (Pgp), Immunofluorescence microscopy using the monoclonal antibody C219 revealed an increase of Pgp expression in almost all hepatocytes after 3 to 8 days of feeding mice DDC- and GF-containing diets. However, after approximately 4 weeks of DDC and approximately 8 weeks of GF feeding, when the first small MBs appeared and loosening and diminution of keratin intermediate filament (KIF) cytoskeleton occurred in some hepatocytes, a decrease or loss of Pgp staining in affected hepatocytes was observed. After feeding mice DDC for 6 week and GF for 12 weeks, many hepatocytes contained MBs and displayed a disruption of the immunohistochemically demonstrable KIF meshwork Double immunofluorescence microscopy with the keratin polyclonal antibody and the mab C219 at this time point revealed a complete loss of Pgp staining in affected cells, although remaining hepatocytes with unaltered KIF meshwork showed a strong reaction with the C219 antibody, Northern blot analyses revealed a significant increase of mdr2 mRNA and, to a lesser extent, of mdr1a mRNA in the Livers of DDC- and GF-fed animals. C1 NCI,EXPTL CARCINOGENESIS LAB,NIH,BETHESDA,MD. RP Preisegger, KH (reprint author), GRAZ UNIV,SCH MED,DEPT PATHOL,AUENBRUGGERPL 25,A-8036 GRAZ,AUSTRIA. NR 50 TC 8 Z9 8 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 JUL PY 1996 VL 24 IS 1 BP 248 EP 252 DI 10.1002/hep.510240139 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UW635 UT WOS:A1996UW63500039 PM 8707270 ER PT J AU Grogan, L Behan, KA Johnston, PG AF Grogan, L Behan, KA Johnston, PG TI Recent advances in the biology of colorectal cancer SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE replication errors; adenomatous polyposis coli; tumor suppressor genes; oncogenes; cytokeratins ID FAMILIAL ADENOMATOUS POLYPOSIS; NONPOLYPOSIS COLON-CANCER; GERM-LINE MUTATIONS; CARCINOEMBRYONIC ANTIGEN CEA; MISMATCH REPAIR DEFICIENCY; RAS GENE-MUTATIONS; CELL-CYCLE CONTROL; APC GENE; MICROSATELLITE INSTABILITY; TUMOR-CELLS AB The identification of the precise molecular defects responsible for the common forms of inherited colorectal cancer has significantly advanced our understanding of both inherited and sporadic disease, These advances coupled with a rapid accumulation of information on the molecular genotype and biological phenotype of colorectal cancer have identified potential. markers that may prove to be not only of prognostic value but also important as screening tools and therapeutic targets. These molecular and biological features include replication errors, mutations of oncogenes and tumor suppressor genes and expression of tumor specific antigens and cytokeratins. This review highlights important recent advances that further our understanding of the biology and genetics of colorectal cancer. C1 NCI,NAVY MED ONCOL BRANCH,NATL NAVAL MED CTR,BETHESDA,MD 20889. NR 156 TC 5 Z9 5 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 1996 VL 11 IS 3 BP 807 EP 820 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA UZ716 UT WOS:A1996UZ71600024 PM 8839768 ER PT J AU Schaffer, AA AF Schaffer, AA TI Faster linkage analysis computations for pedigrees with loops or unused alleles SO HUMAN HEREDITY LA English DT Article DE genetic linkage analysis; algorithms; loops; unknown genotypes ID MUSCULAR-DYSTROPHY; HUMANS; REGION AB There seems to be no limit to the complexity of computations that genetic linkage analysts want to do, Two primary factors that increase the length of computations are pedigree loops and unknown genotypes. I describe the implementation in FASTLINK of some algorithmic improvements to partly address the problems of pedigree loops and unknown genotypes. LINKAGE is by far the most popular software package to do lod score computations on disease pedigrees. FASTLINK is derived from LINKAGE 5.1 and compatible with it. In contrast to LINKAGE, FASTLINK has the virtues that it is faster sequentially, runs well in parallel, is more robust against errors, and includes substantial new documentation, One of the new improvements allows the detection of violation of mendelian rules of inheritance in input pedigree files with loops. This error-detection capability was not provided in any previous version of LINKAGE or FASTLINK. C1 RICE UNIV,DEPT COMP SCI,HOUSTON,TX 77251. RP Schaffer, AA (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 38A,ROOM 8N805,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. RI Schaffer, Alejandro/F-2902-2012 NR 26 TC 107 Z9 109 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD JUL-AUG PY 1996 VL 46 IS 4 BP 226 EP 235 DI 10.1159/000154358 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA UT843 UT WOS:A1996UT84300009 PM 8807326 ER PT J AU Raben, N Nichols, RC Martiniuk, F Plotz, PH AF Raben, N Nichols, RC Martiniuk, F Plotz, PH TI A model of mRNA splicing in adult lysosomal storage disease (glycogenosis type II) SO HUMAN MOLECULAR GENETICS LA English DT Article ID ACID-ALPHA-GLUCOSIDASE; SMALL NUCLEAR RIBONUCLEOPROTEIN; PRE-MESSENGER-RNA; POLYPYRIMIDINE TRACT; MISSENSE MUTATION; IDENTIFICATION; INTRONS; PROTEIN; ONSET; GENE AB Glycogenosis type II is a recessively inherited disorder caused by mutations in the acid maltase (GAA) gene. Clinically, three different phenotypes are recognized: infantile, juvenile and adult forms, A majority of compound heterozygous adult-onset patients carry a t-13g mutation in intron 1 associated with splicing out the first coding exon (exon 2), We have studied the mechanism of this mutation in a model system with wild-type and mutant minigenes expressed in a GAA deficient cell line, We have demonstrated that the mutation does not prevent normal splicing; low levels of correctly spliced mRNA are generated with the mutant construct, The data explain why the mutation is restricted to a milder, adult-onset phenotype, We also demonstrate that splicing out of exon 2 occurs with the wild-type construct, and thus represents alternative splicing which takes place in normal cells. Three splice variants (SV1, SV2 and SV3) are made with both the mutant and the wild-type constructs, Furthermore, as shown by RNAse protection assay, these mRNA variants are less abundant with the mutant construct. Thus, a major effect of the mutation appears to be a low splicing efficiency, since the total amount of all the transcripts generated from the mutant construct is reduced compared with the wild type. The removal of similar to 90% of the intron 1 (2.6 kb) sequence resulted in a dramatic increase in the levels of correctly spliced mRNA, indicating that the intron may contain a powerful transcriptional repressor. C1 NIAMSD,NIH,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. NYU,MED CTR,DEPT MED,DIV PULM,NEW YORK,NY 10016. NR 35 TC 40 Z9 40 U1 0 U2 0 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 JUL PY 1996 VL 5 IS 7 BP 995 EP 1000 DI 10.1093/hmg/5.7.995 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VE062 UT WOS:A1996VE06200018 PM 8817337 ER PT J AU Alexander, NJ AF Alexander, NJ TI Sexual spread of HIV infection SO HUMAN REPRODUCTION LA English DT Article DE anal sex; contraceptives; heterosexual; HIV transmission; vaginal ID HUMAN-IMMUNODEFICIENCY-VIRUS; HETEROSEXUAL ANAL INTERCOURSE; TRANSMITTED DISEASES; CHLAMYDIA-TRACHOMATIS; CONTRACEPTIVE USE; SEMINAL PLASMA; GENITAL-TRACT; NAIROBI PROSTITUTES; POSITIVE PARTNERS; PROCESSED SEMEN AB Over 80% of human immunodeficiency virus (HIV) infections are acquired by heterosexual intercourse yet the mechanism of transmission is poorly understood, This situation makes development of adequate prevention approaches difficult, Virus is shed from infected individuals into both the ejaculate and cervico-vaginal fluids, The site of virus release in the reproductive tract is unclear and requires further study, The ecosystem of the vagina is affected by age, sexual excitement and intercourse, effects of steroid hormones on the genital tract, menses, differences in host susceptibility, contraceptive practices, and other systemic diseases, These factors may affect both shedding and the risk of becoming infected, Contraceptives can affect HIV transmission, Condoms, when used consistently and correctly, protect against infection by preventing direct contact between the penis and vagina, The situation with spermicides is less clear since they can cause irritation which could enhance transmission, Studies on other contraceptive methods are incomplete, The presence of sexually transmitted diseases (STDs) can enhance the risk of HIV infection, This may be due to receptors on the pathogens, the presence of genital ulcers or induced immunosuppression. A recent study demonstrated that treatment for STDs reduced HIV incidence by 40%, This paper will summarize current knowledge on sexual transmission of HIV and list areas where more research is needed. RP Alexander, NJ (reprint author), NICHHD, CONTRACEPT DEV BRANCH, CTR POP RES, NIH, BETHESDA, MD 20852 USA. NR 108 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 1996 VL 11 IS 7 SU S BP 111 EP 120 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA VP551 UT WOS:A1996VP55100012 ER PT J AU Rautaharju, PM Manolio, TA Siscovick, D Zhou, SH Gardin, JM Kronmal, R Furberg, CD Borhani, NO Newman, A AF Rautaharju, PM Manolio, TA Siscovick, D Zhou, SH Gardin, JM Kronmal, R Furberg, CD Borhani, NO Newman, A TI Utility of new electrocardiographic models for left ventricular mass in older adults SO HYPERTENSION LA English DT Article DE electrocardiography; echocardiography; hypertrophy; risk factors; aging; obesity ID ECHOCARDIOGRAPHIC MEASUREMENTS; CARDIOVASCULAR HEALTH; HEART-DISEASE; HYPERTROPHY; CRITERIA; VALIDATION; PREVALENCE; PREDICTION; SIZE; RISK AB Several multivariate statistical models have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements. The validity of these algorithms has not been adequately evaluated. The objective of this investigation was to compare the associations between echocardiographic and electrocardiographic left ventricular mass values with clinical and subclinical indexes of coronary heart disease. The evaluation was performed with participants of the Cardiovascular Health Study, a population-based sample of 5201 men and women aged 65 years and older. Echocardiographic M-mode measurements of left ventricular mass were performed from videotape recordings with the use of a strictly standardized protocol. Electrocardiographic algorithms of the Novacode program and new algorithms derived from the Cardiovascular Health Study population were used for left ventricular mass prediction. Echocardiographic and electrocardiographic determinations of left ventricular mass were technically successful in 3410 (65.6%) and 5013 (96.4%) participants, respectively. The Novacode model overestimated echocardiographic left ventricular mass. Compared with the Novacode model, the new Cardiovascular Health Study electrocardiographic model, which includes adjust ment for body weight, eliminated Left ventricular mass prediction bias and improved the correlation between echocardiographic and electrocardiographic left ventricular mass from .33 to .54 in women and from .46 to .51 in men. Echocardiographic and electrocardiographic models both demonstrated similar and about equally strong associations with overt and subclinical disease and with risk factors for left ventricular hypertrophy. These observations demonstrate the potential utility of electrocardiographic models for left ventricular mass estimation. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA. ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,DIV CARDIOL,ST LOUIS,MO. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV CALIF DAVIS,SCH MED,DEPT INTERNAL MED,DAVIS,CA 95616. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 48 TC 49 Z9 51 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 1996 VL 28 IS 1 BP 8 EP 15 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UW743 UT WOS:A1996UW74300003 PM 8675268 ER PT J AU Xu, QB Fawcett, TW Udelsman, R Holbrook, NJ AF Xu, QB Fawcett, TW Udelsman, R Holbrook, NJ TI Activation of heat shock transcription factor 1 in rat aorta in response to high blood pressure SO HYPERTENSION LA English DT Article DE gene expression; heat shock proteins stress; transcription, genetic ID AGE-DEPENDENT RESPONSE; PROTEIN-70 EXPRESSION; MOLECULAR CHAPERONES; ADRENAL-GLAND; STRESS; CELLS; ENDOCRINE; BRAIN AB We have previously demonstrated that acute hypertension induces heat shock protein gene expression in rat arterial wall. Here we provide evidence that this induction is mediated through the activation of heat shock transcription factor 1 in response to high blood pressure. Rats subjected to restraint or immobilization stress displayed an acute elevation in systolic pressure accompanied by an increase in heat shock protein 70 mRNA expression. Consistent with the rapid time course of mRNA induction, an increase in binding activity to an oligonucleotide encompassing a consensus heat shock element sequence was seen in protein extracts from aorta of restrained rats as assessed with gel mobility shift assays. A similar increase in DNA binding activity was also observed in aortic extracts from rats treated with various hypertensive agents, including phenylephrine, angiotensin II, and vasopressin. That the DNA binding activity was attributed to heat,shock factor 1 was shown through use of antibodies to the transcription factor that retarded the DNA-protein complexes in gel mobility supershift assays. Western blot analysis of heat shock factor 1 protein expression in aortic extracts showed a slower mobility form of the protein in hypertensive rats, indicative of an activated, presumably phosphorylated, form of the transcription factor. These findings support the view that heat shock factor 1 is responsible for induction of heat shock protein 70 in the arterial wall during acute hypertension, a response that is likely to play an important role in protecting arteries during hemodynamic stress. C1 NIA,SECT GENE EXPRESS & AGING,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV HOSP,DIV ENDOCRINE SURG,BALTIMORE,MD. NR 33 TC 24 Z9 27 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 1996 VL 28 IS 1 BP 53 EP 57 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UW743 UT WOS:A1996UW74300010 PM 8675264 ER PT J AU Dahl, CA Strausberg, RL AF Dahl, CA Strausberg, RL TI Revolutionizing biology through leveraging technology SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; HUMAN GENOME; HUMAN DNA; AMPLIFICATION; INVITRO; CLONING RP Dahl, CA (reprint author), NIH,NATL CTR HUMAN GENOME RES,38 LIB DR, MSC6050,BLDG 38A,ROOM 604,BETHESDA,MD 20892, USA. NR 28 TC 3 Z9 3 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 1996 VL 15 IS 4 BP 106 EP 110 DI 10.1109/51.511994 PG 5 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA UW423 UT WOS:A1996UW42300022 ER PT J AU Hilbert, DM Migone, TS Kopf, M Leonard, WJ Rudikoff, S AF Hilbert, DM Migone, TS Kopf, M Leonard, WJ Rudikoff, S TI Distinct tumorigenic potential of abl and raf in B cell neoplasia: abl activates the IL-6 signaling pathway SO IMMUNITY LA English DT Article ID MULTIPLE-MYELOMA PATIENTS; MONOCLONAL LYMPHOCYTES-B; MALIGNANT PLASMA-CELL; BONE-MARROW; HUMAN INTERLEUKIN-6; PERIPHERAL-BLOOD; LINEAGE CELLS; V-ABL; C-ABL; MURINE PLASMACYTOMAGENESIS AB The development of murine plasma cell tumors induced by raf/myc containing retroviruses is facilitated by T cells and completely dependent on IL-6. To determine whether kinases with differing specificities reflect alternative biochemical pathways in B cell tumorigenesis, we have employed an abl/myc containing retrovirus to assess neoplastic development. In contrast with raf/myc, abl/myc disease is T cell and IL-6 independent. An examination of the IL-6 signal transduction pathway reveals that this pathway, as defined by activation of Stat3, is inducible by IL-6 in raf/myc tumors but constitutively activated in abl/myc tumors. These findings provide a mechanism for the derivation of cytokine-independent plasma cell tumors and suggest that both IL-6-dependent and independent tumors may arise in vivo depending on the particular mutational events incurred during tumorigenesis. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. BASEL INST IMMUNOBIOL,CH-4005 BASEL,SWITZERLAND. RP Hilbert, DM (reprint author), NCI,GENET LAB,NIH,BETHESDA,MD 20892, USA. NR 77 TC 33 Z9 33 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1996 VL 5 IS 1 BP 81 EP 89 DI 10.1016/S1074-7613(00)80312-X PG 9 WC Immunology SC Immunology GA UZ454 UT WOS:A1996UZ45400009 PM 8758897 ER PT J AU Coe, JE Prince, GA AF Coe, JE Prince, GA TI Definition of cotton rat immunoglobulins: Sigmodon species differ in expression of IgG isotypes and production of respiratory syncytial virus antibody SO IMMUNOLOGY LA English DT Article ID SUBUNIT VACCINE; PATHOGENESIS; INFECTION; HAMSTER; TYPE-3 AB The cotton rat (Sigmodon species) is the preferred animal model for experiments with a number of human pathogens, especially the respiratory viruses. The cotton rat is classified in the family Cricetidae (with hamsters and gerbils) and is a distant cousin of the common laboratory rat (Rattus) classified in the family Muridae (with the common laboratory mouse, Mus). Antibody reagents that are specific for cotton rat immunoglobulins have not been described. To enhance the usefulness of this model, four immunoglobulins in Sigmodon serum were characterized (IgG1, IgG2, IgA, IgM) and antisera specific for each immunoglobulin were made. Sera from three different species of Sigmodon were examined, S. hispidus (SH), S. arizoni (SA) and S. fulviventer (SF). Although IgA and IgM appeared similar in all three species, the IgG were expressed differently because normal serum levels of IgG2 were deficient in SH when compared with SA and SF and to other rodents. Similarly, IgG2 antibody response to purified protein antigen was deficient in SH although the IgG1 antibody response was superior to that in SF and SA. The three cotton rat species were infected with respiratory syncytial virus, and the kinetics of the antibody response was measured. Neutralizing antibody developed faster and to a higher titre in SH than in SA and SF. The enhanced immunoresponsiveness in SH may compensate for the IgG2 deficiency in SH and these changes appear to be relatively recent events in the evolution of this most populous species of Sigmodon. C1 VIR SYST INC,ROCKVILLE,MD. RP Coe, JE (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 1996 VL 88 IS 3 BP 323 EP 330 DI 10.1046/j.1365-2567.1996.d01-678.x PG 8 WC Immunology SC Immunology GA UW266 UT WOS:A1996UW26600001 PM 8774346 ER PT J AU Kaslow, DC Kumar, S AF Kaslow, DC Kumar, S TI Expression and immunogenicity of the C-terminus of a major blood-stage surface protein of Plasmodium vivax, Pv200(19), secreted from Saccharomyces cerevisiae SO IMMUNOLOGY LETTERS LA English DT Article DE Plasmodium vivax; congenic; merozoite surface protein 1; vaccine ID MALARIA AB The carboxy-terminus of the major merozoite surface protein of Plasmodium has been shown to be the target of protective immunity in a number of non-vivax malaria parasite species. In an effort to develop a protective vaccine for Plasmodium vivax, the most prevalent form of human malaria, we expressed in Saccharomyces cerevisiae the 19-kDa a carboxy-terminus of Pv200 as a His(6)-tagged, secreted polypeptide. Five of seven H-2 congenic mouse strains elicited antibodies that recognized yeast produced PV200(19) by ELISA. The vaccine appears to be immunogenic and widely recognized, and to contain one or more helper T cell epitopes that may allow boosting with subsequent natural infections. C1 NIAID,MALARIA VACCINES SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 10 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUL PY 1996 VL 51 IS 3 BP 187 EP 189 DI 10.1016/0165-2478(96)02570-9 PG 3 WC Immunology SC Immunology GA UY722 UT WOS:A1996UY72200009 PM 8832290 ER PT J AU Yamazaki, K Lehr, JE Rhim, JS Pienta, KJ AF Yamazaki, K Lehr, JE Rhim, JS Pienta, KJ TI Establishment of an immortalized Copenhagen rat bone marrow endothelial cell line SO IN VIVO LA English DT Article DE bone marrow; endothelial cell; Copenhagen rat; immortalization; adenovirus-12 SV40 hybrid virus ID PROSTATIC-CANCER; CULTURE; ADHESION; IDENTIFICATION; METASTASIS; EXPRESSION; INTEGRIN AB Bone marrow endothelial cells are critical mediators in the processes of cell trafficking as well as cancer metastasis, however few established models exist. An immortal cell line of Copenhagen rat bone marrow endothelium was established after infection of primary cultured cells with Adenovirus-12 SV40 hybrid virus and designated YPBE-1. The established cell line has continued to proliferate more than 70 population doublings and has not undergone ''crisis''. It stains positively for SV40 T-antigen in its nuclei by immunohistochemistry and grows in a monolayer with a cobblestone appearance. It demonstrates Dil-Ac-LDL uptake as an endothelial marker. YPBE-1 does not express Integrin beta 3 or endothelin, but does express Integrin alpha 6 beta 1 on the plasma membrane and demonstrates tube formation in Matrigel. This cell line of rat bone marrow endothelial origin should be useful for studying mechanisms of bone metastasis and cell trafficking. C1 UNIV MICHIGAN,MICHIGAN PROSTATE INST,CTR COMPREHENS CANC,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DIV HEMATOL ONCOL,ANN ARBOR,MI 48109. NCI,FREDERICK,MD 21702. RI Pienta, Kenneth/E-7679-2015 OI Pienta, Kenneth/0000-0002-4138-2186 FU NCI NIH HHS [P50 CA69568] NR 28 TC 3 Z9 3 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JUL-AUG PY 1996 VL 10 IS 4 BP 459 EP 462 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VA847 UT WOS:A1996VA84700011 PM 8839795 ER PT J AU Konadu, E Shiloach, J Bryla, DA Robbins, JB Szu, SC AF Konadu, E Shiloach, J Bryla, DA Robbins, JB Szu, SC TI Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to Tetanus toxoid, with emphasis on the role of O acetyls SO INFECTION AND IMMUNITY LA English DT Article ID VI-CAPSULAR POLYSACCHARIDE; SHIGELLA-DYSENTERIAE TYPE-1; TYPHOID-FEVER; CHOLERA-TOXIN; SEROGROUP-A; CHILDREN; ANTIBODIES; BACTEREMIA; VACCINES; OLIGOSACCHARIDE AB Salmonella paratyphi A, the second most common cause of enteric fever in Southeast Asia, is a habitant of and a pathogen for humans only. Lipopolysaccharides (LPS) are both essential virulence factors and protective antigens for systemic infections caused by groups A, B, C, and D nontyphoidal salmonellae. The O-specific polysaccharide of S. paratyphi A is composed of a trisaccharide, -->2-alpha-D-Manp-(1-->4)-alpha-L-Rhap-(1-->3)-alpha-D-Galp-(1-->, with a branch of D-paratose from the C-3 of alpha-D-mannose, and the C-3 of beta-L-rhamnose is partially O acetylated (C. G. Hellerqvist, B. Lindberg, K. Samuelsson, and A. A. Lindberg, Acta Chem. Scand. 25:955-961, 1971). On the basis of data from our investigational vaccines for enteric bacterial pathogens, including group B salmonellae (D. C. Watson, J. B. Robbins, and S. C. Szu, Infect. Immun. 60:4679-4686, 1992), conjugates composed of the detoxified LPS of S. paratyphi A bound to tetanus toxoid (TT) were prepared by several schemes. LPS was detoxified with acetic acid or with hydrazine; the latter removed O acetyls from the O-specific polysaccharide. The detoxified polysaccharides were activated with cyanogen bromide (CNBr) or with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to TT with or without a spacer. Solutions of 2.5 mu g of saccharide, alone or as a conjugate, were injected subcutaneously into young mice, and LPS and TT antibodies were measured by enzyme-linked immunosorbent assaying. A conjugate synthesized with higher-molecular-weight O-SP elicited the highest anti-LPS levels. Only conjugates with O acetyls elicited serum immunoglobulin G anti-LPS with bactericidal activity. There were no statistically significant differences between LPS antibody levels elicited by conjugates synthesized with or without a spacer. The conjugate with O-specific polysaccharide activated by CDAP and bound to TT without a spacer elicited the highest level of TT antibodies. Clinical evaluation of S. paratyphi A conjugates is planned. C1 NIDDKD,NICHHD,NIH,BETHESDA,MD 20892. NIDDKD,BIOTECHNOL UNIT,NIH,BETHESDA,MD 20892. NR 76 TC 49 Z9 55 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1996 VL 64 IS 7 BP 2709 EP 2715 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UT657 UT WOS:A1996UT65700046 PM 8698499 ER PT J AU Shi, YP Sayed, U Qari, SH Roberts, JM Udhayakumar, V Oloo, AJ Hawley, WA Kaslow, DC Nahlen, BL Lal, AA AF Shi, YP Sayed, U Qari, SH Roberts, JM Udhayakumar, V Oloo, AJ Hawley, WA Kaslow, DC Nahlen, BL Lal, AA TI Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1 SO INFECTION AND IMMUNITY LA English DT Article ID INHIBIT PARASITE GROWTH; MONOCLONAL-ANTIBODIES; MALARIA TRANSMISSION; BLOOD STAGES; FRAGMENT; ANTIGEN; INVASION; PRECURSOR; MSP1 AB We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen. C1 NCID,CTR DIS CONTROL & PREVENT,MOL VACCINE SECT,DIV PARASIT DIS,CHAMBLEE,GA 30341. KENYA GOVT MED RES CTR,VECTOR BIOL & CONTROL RES CTR,KISUMU,KENYA. NIAID,MALARIA RES LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI37543-01] NR 28 TC 99 Z9 101 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1996 VL 64 IS 7 BP 2716 EP 2723 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UT657 UT WOS:A1996UT65700047 PM 8698500 ER PT J AU Rathman, M Sjaastad, MD Falkow, S AF Rathman, M Sjaastad, MD Falkow, S TI Acidification of phagosomes containing Salmonella typhimurium in murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID COXIELLA-BURNETII; ACIDIC PH; VIRULENCE; CELLS; INFECTION; MAINTAIN; SURVIVAL; MUTANTS; GROWTH AB Salmonella species are facultative intracellular pathogens. Following entry into mammalian host cells, they reside in membrane-bound vacuoles, resist killing, and replicate. In this work, we investigated the importance of phagosomal pH in the ability of Salmonella typhimurium to survive and replicate within macrophages. Intraphagosomal pH was measured in situ by recording the fluorescence intensity of a pH-sensitive probe, DM-NERF dextran. The majority of vacuoles containing S. typhimurium (live, heat killed, or formalin fixed) acidified from pH greater than or equal to 6.0 to between pH 4.0 and 5.0 within 60 min after formation. In contrast, Mycobacterium avium-containing vacuoles failed to acidify even at later time points. Acidification of S. typhimurium-containing vacuoles was completely blocked by treatment of host cells with bafilomycin A(1), a specific inhibitor of vacuolar proton-ATPases. Bafilomycin inhibition of vacuolar acidification from the onset of infection significantly decreased the survival of S. typhimurium in macrophages. Furthermore, bafilomycin treatment at 2, 4, 8, or even 12 h postinfection decreased the percentage of recoverable bacteria by up to 20-fold. Loss of bacterial viability was seen with several other reagents which, like bafilomycin, raise the pH of phagosomal compartments but are not directly lethal to the bacteria or host cells. Thus, we conclude that Salmonella-containing phagosomes acidify soon after formation and hypothesize that an acidic environment is necessary for survival and replication of the bacteria within the macrophage. C1 STANFORD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,STANFORD,CA 94305. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. RP Rathman, M (reprint author), STANFORD UNIV,SCH MED,DEPT IMMUNOL & MICROBIOL,FAIRCHILD D309,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI26195] NR 40 TC 188 Z9 189 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1996 VL 64 IS 7 BP 2765 EP 2773 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UT657 UT WOS:A1996UT65700053 PM 8698506 ER PT J AU Waterman, SR Small, PLC AF Waterman, SR Small, PLC TI Characterization of the acid resistance phenotype and rpoS alleles of Shiga-like toxin-producing Escherichia coli SO INFECTION AND IMMUNITY LA English DT Article ID SIGMA-FACTOR KATF; GENE AB Shiga-like toxin-producing Escherichia coli (SLTEC) strains are an important group of enteric pathogens. In this study we have examined the abilities of 58 SLTEC isolates to survive at pH 2.5 and found 13 of these isolates to be defective in acid resistance. Introduction of rpoS on a plasmid conferred acid resistance to the majority of the acid-sensitive isolates. The rpoS genes from two of these isolates were sequenced; both isolates contained lesions in the rpoS gene resulting in a nonfunctional RpoS. These results shaw that mutant rpoS alleles exist in natural populations off. coli. Such mutations may play an important role in determining the infective dose of SLTEC and suggest that isolates may vary in infectivity. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. NR 19 TC 103 Z9 105 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1996 VL 64 IS 7 BP 2808 EP 2811 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UT657 UT WOS:A1996UT65700060 PM 8698513 ER PT J AU Jonas, WB Rapoza, CP Blair, WF AF Jonas, WB Rapoza, CP Blair, WF TI The effect of niacinamide on osteoarthritis: A pilot study SO INFLAMMATION RESEARCH LA English DT Article DE niacinamide; randomized controlled trial; osteoarthritis ID OSTEO-ARTHRITIS; DRUGS AB Objective: To evaluate the effect of niacinamide, on selected parameters of osteoarthritis using a double-blind, placebo controlled study design. Methods: Seventy two patients with osteoarthritis were randomized for treatment with niacinamide or an identical placebo for 12 weeks. Outcome measures included global arthritis impact and pain, joint range of motion and flexibility, erythrocyte sedimentation rate, complete blood count, liver function tests, cholesterol, uric acid, and fasting blood sugar. Compliance was monitored with a pill record sheet and interview. Results: Global arthritis impact improved by 29% (95% confidence interval [CI] 6, 46) in subjects on niacinamide and worsened by 10% in placebo subjects (p = 0.04). Pain levels did not change but those on niacinamide reduced their anti-inflammatory medications by 13% (95% CI 9, 94; p = 0.01). Niacinamide reduced erythrocyte sedimentation rate by 22% (95% CI 6, 51; p < 0.005) and increased joint mobility by 4.5 degrees over controls (8 degrees vs. 3.5 degrees; p = 0.04). Side effects were mild but higher in the niacinamide group (40% vs 27%, p = 0,003). Conclusion: This study indicates that niacinamide may have a role in the treatment of osteoarthritis. Niacinamide improved the global impact of osteoarthritis, improved joint flexibility, reduced inflammation, and allowed for reduction in standard anti-inflammatory medications when compared to placebo. More extensive evaluation of niacinamide in arthritis is warranted. C1 DEWITT ARMY COMMUNITY HOSP,FT BELVOIR,VA. RP Jonas, WB (reprint author), NIH,OFF ALTERNAT MED,BLDG 10,BETHESDA,MD 20892, USA. NR 16 TC 41 Z9 45 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD JUL PY 1996 VL 45 IS 7 BP 330 EP 334 DI 10.1007/BF02252945 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UY056 UT WOS:A1996UY05600004 PM 8841834 ER PT J AU Georgiou, P Maroulakou, IG Green, JE Dantis, P RomanoSpica, V Kottaridis, S Lautenberger, JA Watson, DK Papas, TS Fischinger, PJ Bhat, NK AF Georgiou, P Maroulakou, IG Green, JE Dantis, P RomanoSpica, V Kottaridis, S Lautenberger, JA Watson, DK Papas, TS Fischinger, PJ Bhat, NK TI Expression of ets family of genes in systemic lupus erythematosus and Sjogren's syndrome SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ETS family of transcription factors; systemic lupus erythematosus; Sjogren's syndrome; lymphocytes ID INTERLEUKIN-2 RECEPTOR LEVELS; BLOOD MONONUCLEAR-CELLS; ONCOGENE EXPRESSION; DNA-BINDING; AUTOIMMUNE-DISEASES; T-CELLS; ACTIVATION; FLI-1; MICE; TRANSLOCATION AB We have examined the expression of three members of the ets family of genes, ETS1, ETS2 and ERGB/Fli-1, in lymphocytes from patients with systemic lupus erythematosus and in two murine autoimmune model systems. The ERGB/Fli-1 gene is expressed at a higher level in lymphocytes from autoimmune disease patients than healthy individuals. In addition, we found that the ERGB/Fli-1 gene expression is higher in splenic T-cells from lupus prone mice and in infiltrating lymphocytes in the salivary glands of HTLV-I tax transgenic mice. Taken together, these results suggest that the elevated expression of the ERGB/Fli-1 gene in lymphocytes may be a prelude to the development of autoimmune diseases. C1 NCI, FREDERICK CANC RES & DEV CTR, SCI APPLICAT INT CORP, ONCOL MOLEC LAB, FREDERICK, MD 21702 USA. EVANGELISMOS MED CTR, DEPT RHEUMATOL, ATHENS, GREECE. UCSC, FAC MED, INST HYG, ROME, ITALY. HELLENIC ANTICANC INST, PAPANICOLAOU RES CTR ONCOL & EXPT SURG, ATHENS, GREECE. MED UNIV S CAROLINA, HOLLINGS CANC CTR, CTR MOL & STRUCT BIOL, CHARLESTON, SC USA. UNIV IOANNINA, SCH MED, DEPT INTERNAL MED, GR-45110 IOANNINA, GREECE. NR 44 TC 47 Z9 48 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUL PY 1996 VL 9 IS 1 BP 9 EP 18 PG 10 WC Oncology SC Oncology GA UT656 UT WOS:A1996UT65600002 PM 21541474 ER PT J AU Shrayer, D Park, CH Kouttab, N Bogaars, H McInnis, R Paul, SR Maizel, A Hearing, VJ Wanebo, HJ AF Shrayer, D Park, CH Kouttab, N Bogaars, H McInnis, R Paul, SR Maizel, A Hearing, VJ Wanebo, HJ TI Intrasplenic vaccination against experimental melanoma SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE intrasplenic vaccination; melanoma immunity ID FORMALINIZED EXTRACELLULAR ANTIGENS; AUTOREACTIVE T-CELLS; NATURAL-KILLER CELLS; MURINE MELANOMA; NUDE-MICE; RECOMBINANT INTERLEUKIN-2; TUMOR REJECTION; THERAPY; B700; ANTIBODIES AB The immunodominant component of a formalinized extracellular antigen (fECA) vaccine prepared from B16 F10 melanoma cells is the melanoma-associated antigen B700. We now demonstrate that a single prophylactic intrasplenic inoculation of B700 antigen (1-10 mu g) stimulates the production of antibodies which have antiproliferative effects on B16 F10 melanoma cells in vitro. In addition, potential cytotoxic effects of splenocytes from B700 antigen inoculated mice were evaluated for two cellular immune effector functions, natural killer (NK) cell activity and lymphokine activated killer (LAK) cell activity; both activities were increased following B700 antigen inoculation. Intrasplenic injection of B700 antigen elicited an increase in the expression of the CD25 surface antigen (IL-2 R alpha) by T lymphocytes and up-regulated the expression of IL-2 R alpha mRNA. Thus both humoral and cellular cytotoxic immune responses might play roles in the decreased growth of primary tumors in B700 antigen inoculated mice and in the higher survival rate in this group of animals. C1 ROGER WILLIAMS MED CTR,DEPT SURG,PROVIDENCE,RI 02908. BROWN UNIV,RHODE ISL HOSP,DEPT PEDIAT,PROVIDENCE,RI 02908. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Shrayer, D (reprint author), BROWN UNIV,ROGER WILLIAMS MED CTR,SURG RES LAB,DEPT EXPTL PATHOL,825 CHALKSTONE AVE,PROVIDENCE,RI 02908, USA. NR 40 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 JUL PY 1996 VL 9 IS 1 BP 123 EP 129 PG 7 WC Oncology SC Oncology GA UT656 UT WOS:A1996UT65600019 PM 21541491 ER PT J AU Forsyth, MH Tully, JG Gorton, TS Hinckley, L Frasca, S VanKruiningen, HJ Geary, SJ AF Forsyth, MH Tully, JG Gorton, TS Hinckley, L Frasca, S VanKruiningen, HJ Geary, SJ TI Mycoplasma sturni sp nov, from the conjunctiva of a European starling (Sturnus vulgaris) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GALLISEPTICUM AB Strain UCMF(T) (T = type strain) was isolated from the conjunctiva of a European starling (Sturnus vulgaris) with conjunctivitis. Colonies grown On conventional mycoplasma agar possessed the typical fried-egg appearance observed with many mycoplasmal species. Electron micrographs of ultrathin sections of UCMF(T) revealed a pleomorphic cellular morphology; the cells ranged from spherical to elliptical or flask shaped, The cell size ranged from 0.3 to 0.5 mu m. Strain UCMF(T) grows well in a variety of mycoplasma broth formulations at 25 degrees C, with rapid and heavy growth at 37 degrees C, No growth occurs at 42 degrees C. This organism ferments glucose but does not hydrolyze urea or arginine and has an absolute requirement for sterol for growth. Strain UCMF(T) does not hemagglutinate or hemadsorb chicken erythrocytes, The genome size is 870 kbp, and the guanine-plus-cytosine content is 31 mol%. Sequence analysis of the 16S rRNA gene demonstrated that this organism is unique and has not been described previously. Serological analysis confirmed that strain UCMF(T) is distinct from all previously identified Mycoplasma, Acholeplasma, Spiroplasma, Entomoplasma, and Mesoplasma species. This organism represents a new species, for which we propose the name Mycoplasma sturni. Strain UCMF (= ATCC 51945) is the type strain of M. sturni sp. nov. C1 UNIV CONNECTICUT,DEPT PATHOBIOL,STORRS,CT 06269. UNIV CONNECTICUT,NE RES CTR WILDLIFE DIS,STORRS,CT 06269. NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,FREDERICK,MD 21702. NR 21 TC 16 Z9 16 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1996 VL 46 IS 3 BP 716 EP 719 PG 4 WC Microbiology SC Microbiology GA UW652 UT WOS:A1996UW65200016 PM 8782681 ER PT J AU Whitcomb, RF Gasparich, GE French, FE Tully, JG Rose, DL Carle, P Bove, JM Henegar, RB Konai, M Hackett, KJ Adams, JR Clark, TB Williamson, DL AF Whitcomb, RF Gasparich, GE French, FE Tully, JG Rose, DL Carle, P Bove, JM Henegar, RB Konai, M Hackett, KJ Adams, JR Clark, TB Williamson, DL TI Spiroplasma syrphidicola sp nov, from a syrphid fly (Diptera: Syrphidae) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CLASS MOLLICUTES; CLASSIFICATION; SUBGROUPS AB Spiroplasma sp. strain EA-1(T) (T = type strain) (subgroup VIII-1), which was isolated from the syrphid by Eristalis arbustorum, was serologically distinct from other spiroplasma species, groups, and subgroups. The cells of this strain, as revealed by dark-field light microscopy, were short, helical, and motile. An electron microscopic examination revealed wall-less cells delimited by a single membrane. The unusually short cells passed through 220-nm filter pores with no reduction in titer. The organisms grew well in SM-1, M1D, and SP-4 liquid media. Growth also occurred in conventional horse serum medium and 1% serum fraction medium. Strain EA-1(T) grew at temperatures between 10 and 41 degrees C, and optimum growth occurred at 32 degrees C. The doubling time at the optimal temperature was 1.0 h. The strain catabolized glucose and hydrolyzed arginine but did not hydrolyze urea. The guanine-plus-cytosine content of the DNA was 30 +/- 1 mol%. The genome size was about 1,230 kbp. Strain EA-1 (= ATCC 33826), which represents subgroup VIII-1, is designated the type strain of a new species, Spiroplasma syrphidicola. C1 GEORGIA SO UNIV,DEPT BIOL,STATESBORO,GA 30460. NIAID,FREDERICK CANC RES FACIL,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. INRA,F-33883 VILLENAVE DORNON,FRANCE. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. RP Whitcomb, RF (reprint author), USDA ARS,BELTSVILLE AGR RES CTR E,INSECT BIOCONTROL LAB,BLDG 465,BELTSVILLE,MD 20705, USA. NR 34 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1996 VL 46 IS 3 BP 797 EP 801 PG 5 WC Microbiology SC Microbiology GA UW652 UT WOS:A1996UW65200028 PM 8782692 ER PT J AU Mahurkar, AA Vivino, MA Trus, BL Kuehl, EM Datiles, MB KaiserKupfer, MI AF Mahurkar, AA Vivino, MA Trus, BL Kuehl, EM Datiles, MB KaiserKupfer, MI TI Constructing retinal fundus photomontages - A new computer-based method SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE fundus photograph montages; fundus photography; gyrate atrophy; retinal image analysis; retinitis pigmentosa ID GYRATE ATROPHY; PHOTOGRAPHS; REGISTRATION AB Purpose. To develop computer algorithms for reconstructing 24-bit color, wide-angle composite retinal fundus images from a set of adjacent 45 degrees fundus slides, The authors present the description, technical details, and results of the image reconstruction technique. Methods. Patients with retinal degeneration underwent fundus photography with a 45 degrees field-of-view fundus camera. Individual photographic slides were digitized for creating fundus montages. Background variations in individual 45 degrees images were modeled to first- or second-order two-dimensional polynomial functions to generate a background image. The background image was subtracted from the original image to obtain background corrected image. Background corrected images were registered and spatially transformed using a first- or second-order two-dimensional polynomial warp model to reconstruct a composite retinal fundus montage. Results. The authors successfully reconstructed 24-bit color, 100 degrees field-of-view, composite retinal fundus images. The computer-reconstructed montages are an improvement over manually generated montages because computer analysis can be performed on the computer-based montages. In addition, background variations and discontinuities between individual photographs observed in manually generated montages are reduced greatly in computer-generated montages. Most important, the computer-generated montages are better aligned than the manually generated photomontages. Conclusions. This method of reconstructing a wide-angle composite retinal fundus image from a set of adjacent small- and wide-angle fundus slides is a new tool for creating montages as large as 100 degrees field of view. The computer-generated montages may be used for documenting and quantifying retinal findings, This can greatly assist studies of retinal manifestations of diseases, such as gyrate atrophy, retinitis pigmentosa, sickle cell disease, and acquired immune deficiency syndrome. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Mahurkar, AA (reprint author), NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,BLDG 10,RM 10N226,10 CTR DR,MSC 1860,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 25 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1996 VL 37 IS 8 BP 1675 EP 1683 PG 9 WC Ophthalmology SC Ophthalmology GA UW831 UT WOS:A1996UW83100025 PM 8675411 ER PT J AU Graziosi, P Rosmini, F Bonacini, M Ferrigno, L Sperduto, RD Milton, RC Maraini, G AF Graziosi, P Rosmini, F Bonacini, M Ferrigno, L Sperduto, RD Milton, RC Maraini, G TI Location and severity of cortical opacities in different regions of the lens in age-related cataract SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cataract risk factors; lens opacity; lens segments; light damage; sunlight exposure index ID BEAVER DAM EYE AB Purpose. To examine the distribution of cortical opacities across the lens in the Italian-American Natural History Study of Age-Related Cataract and to study the association between an index of sunlight exposure and the location of cortical cataract within the lens. Methods. Lens photographs of one eye of 731 persons with cortical opacities (503 with pure and 228 with mixed types of opacity) were included in the analysis. A radial grid superimposed on the photographs was used to assess presence, location, and severity of wedge-shaped cortical opacities. Results. Both the prevalence and the extent of cortical opacities were highest in the inferior-nasal quadrant and lowest in the superior-nasal quadrant of the lens. In polychotomous logistic regression, persons with the greatest excess areal involvement in the inferior half of the lens were more likely to have high exposure to sunlight, as measured by a sunlight index, than persons with excess involvement in the superior half of the lens (odds ratio, 1.73; 95% confidence interval 1.03, 2.93). Excess areal involvement of the inferior lens also was associated with the pure type of cortical cataract and with the total extent of the opacity. Conclusions. Age-related cortical opacities occur more frequently inferiorly than superiorly and, to a lesser extent, nasally than temporally. Possibly higher exposure of these lens segments to sunlight may explain this preferential location of cortical opacities. C1 UNIV PARMA, INST OPHTHALMOL, I-43100 PARMA, ITALY. IST SUPER SANITA, EPIDEMIOL & BIOSTAT LAB, I-00161 ROME, ITALY. NEI, BETHESDA, MD 20892 USA. FU NEI NIH HHS [N 01-EY-9-2108] NR 10 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1996 VL 37 IS 8 BP 1698 EP 1703 PG 6 WC Ophthalmology SC Ophthalmology GA UW831 UT WOS:A1996UW83100028 PM 8675414 ER PT J AU Oyler, J Darwin, WD Cone, EJ AF Oyler, J Darwin, WD Cone, EJ TI Cocaine contamination of United States paper currency SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article RP Oyler, J (reprint author), NIA,ADDICT RES CTR,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 6 TC 39 Z9 40 U1 0 U2 14 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUL-AUG PY 1996 VL 20 IS 4 BP 213 EP 216 PG 4 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA UX944 UT WOS:A1996UX94400001 PM 8835657 ER PT J AU Kuhlman, JJ Magluilo, J Cone, E Levine, B AF Kuhlman, JJ Magluilo, J Cone, E Levine, B TI Simultaneous assay of buprenorphine and norbuprenorphine by negative chemical ionization tandem mass spectrometry SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DEALKYLATED METABOLITE; GAS-CHROMATOGRAPHY; HUMAN-PLASMA; URINE; RADIOIMMUNOASSAY C1 NIDA,DIV INTRAMURAL RES,NIH,BALTIMORE,MD. RP Kuhlman, JJ (reprint author), USAF,INST PATHOL,DIV FORENS TOXICOL,WASHINGTON,DC 20330, USA. NR 20 TC 34 Z9 34 U1 0 U2 1 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUL-AUG PY 1996 VL 20 IS 4 BP 229 EP 235 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA UX944 UT WOS:A1996UX94400004 PM 8835660 ER PT J AU Yee, YC Kisslinger, B Yu, VL Jin, DJ AF Yee, YC Kisslinger, B Yu, VL Jin, DJ TI A mechanism of rifamycin inhibition and resistance in Pseudomonas aeruginosa SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID RIFAMPICIN-RESISTANCE; COMBINATION; MUTATIONS AB We sought to study the nature of rifampicin resistance in Pseudomonas aeruginosa. We hypothesized that the rifamycin regions of RNA polymerase are conserved in P. aeruginosa and that rifampicin resistance is mediated by a mutation in the rpoB gene encoding the beta subunit of RNA polymerase. Transcription assays showed that 50 nM of rifampicin inhibited transcription >99% in a clinical isolate (MIC = 32 mg/L) and only <40% in the rifampicin resistant mutant (MIC = 1000 mg/L). DNA sequencing revealed that the rifampicin regions are conserved in P. aeruginosa and the rifampicin regions of the rifampicin-resistant strain contained a mutation. Sodium hexametaphosphate lowered rifamycin MIC in a rifamycin-resistant mutant four-fold and in the clinical isolate 32-fold, suggesting that P. aeruginosa has a natural membrane barrier to rifamycins. C1 NCI,MOL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15261. CARNEGIE MELLON UNIV,MELLON INST,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DIV INFECT DIS,PITTSBURGH,PA 15213. FU NIGMS NIH HHS [GM 30375] NR 11 TC 12 Z9 12 U1 1 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 1996 VL 38 IS 1 BP 133 EP 137 DI 10.1093/jac/38.1.133 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA VA607 UT WOS:A1996VA60700016 PM 8858465 ER PT J AU Sternberg, KJ Lamb, ME Hershkowitz, I Esplin, PW Redlich, A Sunshine, N AF Sternberg, KJ Lamb, ME Hershkowitz, I Esplin, PW Redlich, A Sunshine, N TI The relation between investigative utterance types and the informativeness of child witnesses SO JOURNAL OF APPLIED DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID SEXUAL ABUSE; STATEMENTS; STRESSFUL; VALIDITY; MEMORY; EVENTS AB Researchers have previously shown that, at least in Israeli investigative interviews, open-ended invitations yield significantly longer and more detailed responses from young witnesses than directive, leading, or suggestive utterances. Detailed psycho-linguistic analyses of 45 interviews of 4- to 12-year-old children by police investigators in the United States confirmed that, as in Israel, invitations yielded longer and richer responses than more focused interviewer utterances. The superiority of invitations was greater when the children reported experiencing three or more, rather than only one, incidents of abuse. Invitations were rarely used, however, and the investigators failed to elicit more information from children who reported multiple incidents of abuse than from children who reported only one incident. C1 NICHHD, SECT SOCIAL & EMOT DEV, BETHESDA, MD 20814 USA. NR 30 TC 87 Z9 87 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0193-3973 J9 J APPL DEV PSYCHOL JI J. Appl. Dev. Psychol. PD JUL-SEP PY 1996 VL 17 IS 3 BP 439 EP 451 DI 10.1016/S0193-3973(96)90036-2 PG 13 WC Psychology, Developmental SC Psychology GA VR067 UT WOS:A1996VR06700008 ER PT J AU Vinella, D Gagny, B JoseleauPetit, D DAri, R Cashel, M AF Vinella, D Gagny, B JoseleauPetit, D DAri, R Cashel, M TI Mecillinam resistance in Escherichia coli is conferred by loss of a second activity of the AroK protein SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PENICILLIN-BINDING PROTEIN-2; SHIKIMATE KINASE-II; CELL-DIVISION GENE; DAM GENE; PPGPP SYNTHESIS; COPY-NUMBER; FTSZ RING; MRE-GENES; ROD SHAPE; MUTANTS AB Mecillinam, a beta-lactam antibiotic specific to penicillin-binding protein 2 (PBP 2) in Escherichia coli, blocks cell wall elongation and, indirectly, cell division, but its lethality can be overcome by increased level of ppGpp, the nucleotide effector of the stringent response, We have subjected an E. coli k-12 strain to random insertional mutagenesis with a mini-Tn10 element, One insertion, which was found to confer resistance to mecillinam in reLA(+) and relA strains, was mapped at 75.5 min on the E. coli map and was located between the promoters and the coding sequence of the aroK gene, which codes for shikimate kinase I, one of two E. coli shikimate kinases, both of which are involved in aromatic amino acid biosynthesis. The mecillinam resistance conferred by the insertion was abolished in a Delta relA Delta spoT strain completely lacking ppGpp, and it thus depends on the presence of ppGpp. Furthermore, the insertion increased the ppGpp pool approximately twofold in a relA(+) strain. However, this increase was not observed in relA strains, although the insertion still conferred mecillinam resistance in these backgrounds, showing that mecillinam resistance is not due to an increased ppGpp pool. The resistance was also abolished in an ftsZ84(Ts) strain under semipermissive conditions, and the aroK::mini-Tn10 allele partially suppressed ftsZ84(Ts); however, it did not increase the concentration of the FtsZ cell division protein, The insertion greatly decreased or abolished the shikimate kinase activity of AroK in vivo and in vitro. The two shikimate kinases of E. coli are not equivalent; the loss of AroK confers mecillinam resistance, whereas the loss of AroL does not. Furthermore, the ability of the aroK mutation to confer mecillinam resistance is shown to be independent of polar effects on operon expression and of effects on the availability of aromatic amino acids or shikimic acid. Instead, we conclude that the AroK protein has a second activity, possibly related to cell division regulation, which confers mecillinam sensitivity. We were able to separate the AroK activities mutationally with an aroK mutant allele lacking shikimate kinase activity but still able to confer mecillinam sensitivity. C1 UNIV PARIS 07, INST JACQUES MONOD, CNRS, F-75251 PARIS 05, FRANCE. RP NICHHD, MOLEC GENET LAB, NIH, BETHESDA, MD 20892 USA. RI vinella, daniel/G-5504-2012 NR 73 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1996 VL 178 IS 13 BP 3818 EP 3828 PG 11 WC Microbiology SC Microbiology GA UU349 UT WOS:A1996UU34900022 PM 8682786 ER PT J AU Yoneyama, M Suhara, W Fukuhara, Y Sato, M Ozato, K Fujita, T AF Yoneyama, M Suhara, W Fukuhara, Y Sato, M Ozato, K Fujita, T TI Autocrine amplification of type I interferon gene expression mediated by interferon stimulated gene factor 3 (ISGF3) SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE gene regulation; IRF; ISGF3; type I interferon; viral induction ID IFN-BETA-GENE; NF-KAPPA-B; VIRUS-INDUCIBLE ENHANCER; TRANSCRIPTION FACTOR; REGULATORY ELEMENTS; SIGNAL TRANSDUCTION; ALPHA-INTERFERON; DNA-SEQUENCES; IRF-1; BINDING AB Interferon regulatory factor (IRF)-1 and IRF-2 have been implicated for the virus-induced expression of the interferon-alpha and beta (type I IFN) genes. However, recent gene disruption studies in mice suggested the presence of other factor(s) interacting with overlapping promoter elements. In the present paper, we describe the characterization of a DNA binding factor which is strongly induced after virus infection and recognizes these promoter elements. After extensive purification, the factor was revealed to be identical to IFN-stimulated gene factor 3 (ISGF3), a transcription factor complex activated by IFN treatment. ISGF3 binds to the promoter element of IFN-beta, positive regulatory domain I (PRDI), with significantly higher affinity than IRF-1, 2, and mutational analysis of PRDI showed that the gene expression and binding of ISGF3, but not of IRF-1, 2, are highly correlated. Furthermore, our functional analysis involving a dominant negative inhibitor for ISGF3 activation and an anti-IFN neutralizing antibody clearly demonstrated the presence of a positive feedback pathway for type I IFN genes mediated by ISGF3. C1 TOKYO METROPOLITAN INST MED SCI,DEPT TUMOR CELL BIOL,BUNKYO KU,TOKYO 113,JAPAN. NICHHD,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. NR 52 TC 98 Z9 99 U1 0 U2 1 PU JAPAN BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD JUL PY 1996 VL 120 IS 1 BP 160 EP 169 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY256 UT WOS:A1996UY25600025 PM 8864859 ER PT J AU Vogel, SS Blank, PS Zimmerberg, J AF Vogel, SS Blank, PS Zimmerberg, J TI Poisson-distributed active fusion complexes underlie the control of the rate and extent of exocytosis by calcium SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SEA-URCHIN EGGS; ADRENAL CHROMAFFIN CELLS; TRANSMITTER RELEASE; SYNAPTIC TRANSMISSION; DEPENDENT EXOCYTOSIS; CORTICAL GRANULES; TRIGGERED FUSION; VESICLE FUSION; FINAL STEPS; SECRETION AB We have investigated the consequences of having multiple fusion complexes on exocytotic granules, and have identified a new principle for interpreting the calcium dependence of calcium-triggered exocytosis. Strikingly different physiological responses to calcium are expected when active fusion complexes are distributed between granules in a deterministic or probabilistic manner. We have modeled these differences, and compared them with the calcium dependence of sea urchin egg cortical granule exocytosis. From the calcium dependence of cortical granule exocytosis, and from the exposure time and concentration dependence of N-ethylmaleimide inhibition, we determined that cortical granules do have spare active fusion complexes that are randomly distributed as a Poisson process among the population of granules. At high calcium concentrations, docking sites have on average nine active fusion complexes. RP Vogel, SS (reprint author), NICHHD,NATL INST HLTH,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 6C-215,10 CTR DR,MSC 1855,BETHESDA,MD 20892, USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 61 TC 38 Z9 39 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1996 VL 134 IS 2 BP 329 EP 338 DI 10.1083/jcb.134.2.329 PG 10 WC Cell Biology SC Cell Biology GA UX946 UT WOS:A1996UX94600006 PM 8707819 ER PT J AU Scidmore, MA Fischer, ER Hackstadt, T AF Scidmore, MA Fischer, ER Hackstadt, T TI Sphingolipids and glycoproteins are differentially trafficked to the Chlamydia trachomatis inclusion SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GOLGI-COMPLEX; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; CELL-SURFACE; INTRACELLULAR-TRANSPORT; ALTERNATIVE PATHWAYS; PHYSICAL-PROPERTIES; HOST-CELLS; TRANSFERRIN; MACROPHAGES AB Chlamydia trachomatis is an obligate intracellular pathogen that multiplies within the confines of a membrane-bound vacuole called an inclusion. Approximately 40-50% of the sphingomyelin synthesized from exogenously added NBD-ceramide is specifically transported from the Golgi apparatus to the chlamydial inclusion (Hackstadt, T., M.A. Scidmore, and D.D. Rockey. 1995. Proc. Natl. Acad. Sci USA. 92: 4877-4881). Given this major disruption of a cellular exocytic pathway and the similarities between glycolipid and glycoprotein exocytosis, we wished to determine whether the processing and trafficking of glycoproteins through the Golgi apparatus to the plasma membrane in chlamydia-infected cells was also disrupted, We analyzed the processing of several model glycoproteins including vesicular stomatitis virus G-protein, transferrin receptor, and human histocompatibility leukocyte class I antigen. In infected cells, the posttranslational processing and trafficking of these specific proteins through the Golgi apparatus and subsequent transport to the plasma membrane was not significantly impaired. C1 NIAID,NIH,HOST PARASITE INTERACT SECT,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. NIAID,NIH,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. NR 46 TC 110 Z9 114 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1996 VL 134 IS 2 BP 363 EP 374 DI 10.1083/jcb.134.2.363 PG 12 WC Cell Biology SC Cell Biology GA UX946 UT WOS:A1996UX94600009 PM 8707822 ER PT J AU Liesi, P Wright, JM AF Liesi, P Wright, JM TI Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CEREBELLAR CORTEX; MOUSE CEREBELLUM; MUTANT MICE; HIPPOCAMPAL-NEURONS; PROMOTING DOMAIN; MIGRATION; CELL; DIFFERENTIATION; SECONDARY; CHIMERAS AB The weaver mutation impairs migration of the cerebellar granular neurons and induces neuronal death during the first two weeks of postnatal life. To elucidate the molecular mechanisms for the impaired neuronal migration, we investigated the rescue mechanisms of the weaver (wv/wv) granule neurons in vitro. We found that Fab(2) fragments of antibodies against a neurite outgrowth domain of the B2 chain of laminin enhanced neurite outgrowth and neuronal migration of the weaver granule neurons on a laminin substratum and in the established cable culture system. The rescue of the weaver granule neurons by antibodies against the B2 chain of laminin may result from the neutralizing effect of these antibodies against the elevated B2 chain levels of the weaver brain. The L-type calcium channel blocker, verapamil (1-5 mu M), also rescued the weaver granule neurons. High concentrations of MK-801 (10-20 mu M), a glutamate receptor antagonist and voltage-gated calcium channel blocker, rescued the weaver granule neurons similar to verapamil, but low concentrations of MK-801 (1 mu M) had no rescue effect, Simultaneous patch-clamp studies indicated that the weaver granule neurons did not express functional N-methyl-D-aspartate receptors further indicating that the rescue of the weaver granule neurons by MK-801 resulted from its known inhibition of voltage-gated calcium channels. The present results indicate that antibodies against the B2 chain of laminin, verapamil, and high concentrations of MK-801 protect the weaver granule neurons from the otherwise destructive action of the weaver gene. Thus, both the laminin system and calcium channel function contribute to the migration deficiency of the weaver granule neurons. RP Liesi, P (reprint author), NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, NIH, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 42 TC 29 Z9 30 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1996 VL 134 IS 2 BP 477 EP 486 DI 10.1083/jcb.134.2.477 PG 10 WC Cell Biology SC Cell Biology GA UX946 UT WOS:A1996UX94600018 PM 8707831 ER PT J AU Criswell, PS Ostrowski, LE Asai, DJ AF Criswell, PS Ostrowski, LE Asai, DJ TI A novel cytoplasmic dynein heavy chain: Expression of DHC1b in mammalian ciliated epithelial cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE cytoplasmic dynein; dynein isoform; ciliogenesis ID MICROTUBULE-ACTIVATED ATPASE; MOTOR PROTEINS; TRANSPORT; ISOFORMS; TESTIS; ENZYME; MAP-1C; GENES; YEAST AB Organisms that have cilia or flagella express over a dozen dynein heavy chain genes. Of these heavy chain genes, most appear to encode axonemal dyneins, one encodes conventional cytoplasmic dynein (MAP1C or DHC1a), and one, here referred to as DHC1b, encodes an unclassified heavy chain, Previous analysis of sea urchin DHC1b (Gibbons et al, (1994) Mel. Biol, Cell 5, 57-70) indicated that this isoform is either an axonemal dynein with an unusual protein sequence or a cytoplasmic dynein whose expression increases during ciliogenesis. In the present study,we examined the expression of DHC1b in rat tissues. The DHC1b gene is expressed in all tissues examined, including unciliated liver and heart cells, In contrast, rat axonemal dyneins are only expressed in tissues that produce cilia or flagella, In cultured rat tracheal epithelial (RTE) cells, DHC1b is expressed in undifferentiated cells and increases in expression during ciliogenesis. In contrast, the expression of conventional cytoplasmic dynein, DHC1a, does not change during RTE differentiation and axonemal dynein is not expressed until after differentiation commences. In order to examine the expression of DHC1b protein, we produced an isoform-specific antibody to a synthetic peptide derived from the rat DHC1b sequence, The antibody demonstrated that DHC1b is a relatively minor component of partially purified cytoplasmic dynein, Indirect immunofluorescence microscopy revealed that DHC1b is not detected in cilia and remains in the cytoplasm of ciliated RTE cells, often accumulating at the apical ends of the cells, These results suggest that DHC1b is a cytoplasmic dynein that may participate in intracellular trafficking in polarized cells. C1 PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NIEHS,AIRWAY CELL BIOL GRP,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 49 TC 48 Z9 50 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1996 VL 109 BP 1891 EP 1898 PN 7 PG 8 WC Cell Biology SC Cell Biology GA UX930 UT WOS:A1996UX93000024 PM 8832411 ER PT J AU Fewell, JW Kuff, EL AF Fewell, JW Kuff, EL TI Intracellular redistribution of Ku immunoreactivity in response to cell-cell contact and growth modulating components in the medium SO JOURNAL OF CELL SCIENCE LA English DT Article DE Ku; intracellular distribution; immunostaining; enucleation; cell contact; serum and Ca2+ depletion; somatostatin; G(1) arrest ID DEPENDENT PROTEIN-KINASE; RNA POLYMERASE-II; DNA-BINDING PROTEINS; AUTOANTIGEN KU; MONOCLONAL-ANTIBODIES; V(D)J RECOMBINATION; GENE-TRANSCRIPTION; 86-KDA SUBUNIT; STRANDED DNA; HELA-CELLS AB Ru is a heterodimeric protein first recognized as a human autoantigen but now known to be widely distributed in mammalian cells. Analysis of repair-deficient mutant cells has shown that Ku is required for DNA repair, and roles in DNA replication and transcription have also been suggested on the basis of in vitro observations, Ku is generally regarded as a nuclear component, However, in the present paper, we show that a quantitatively significant fraction (half or more) of Ku is located in the cytoplasm of cultured primate cells, and that major changes in epitope accessibility of both nuclear and cytoplasmic Ku components are associated with the transition from sparse to conflueut cell densities, The same changes in immunoreactivity were seen in HeLa, 293, CV-1 (monkey) and HPV-transformed keratinocyte cell lines, and in primary cultures of human keratinocytes, The immunostaining pattern of sparsely grown cells could be converted to the 'conflueut' configuration by re-plating them at the same low density on a monolayer of mouse 3T3 cells. The conflueut antigen pattern could also be induced in sparse cells within 15-30 minutes by exposure of the cells to serum- or Ca2+-free medium or overnight with 2 mM hydroxyurea. Somatostatin at 0.12 mM blocked the effects of serum/Ca2+ deprivation on Ku p70 antigen distribution in sparse CV-1 cells, and in confluent cultures reversed the usual nuclear concentration of p70 immunoreactivity, However, somatostatin did not alter the expected immunostaining patterns of p86, Preliminary studies indicate that sparse CV-1 cells, but not HeLa cells, respond to as little as 1 pM of TGF-beta 1 in the culture medium by the rapid appearance of nuclear immunoreactivity, TGF-alpha had no apparent effect. These findings are consistent with the participation of Ku in a signal transduction system responsive to the inhibitory effect of cell-cell contact on the one hand and to cytokines and growth-supportive components of the culture medium on the other. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 60 TC 52 Z9 54 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1996 VL 109 BP 1937 EP 1946 PN 7 PG 10 WC Cell Biology SC Cell Biology GA UX930 UT WOS:A1996UX93000029 PM 8832416 ER PT J AU Jones, TH Torres, JA Spande, TF Garraffo, HM Blum, MS Snelling, RR AF Jones, TH Torres, JA Spande, TF Garraffo, HM Blum, MS Snelling, RR TI Chemistry of venom alkaloids in some Solenopsis (Diplorhoptrum) species from Puerto Rico SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE venom; alkaloids; Solenopsis; Puerto Rico ID POISON FROGS DENDROBATIDAE; PHASE INFRARED-SPECTROSCOPY; FIRE ANT VENOMS; SKIN ALKALOIDS; MONOMORIUM; INDOLIZIDINES; PYRROLIZIDINES; QUINOLIZIDINES; PUMILIOTOXINS; EVOLUTION AB A number of 15-carbon alkaloids have been identified in venom extracts of four Puerto Rican species of ants in the genus Solenopsis (Diplorhoptrum). Workers of a species from El Verde produced the cis and trans isomers of 2-methyl-6-nonylpiperidine with the latter isomer predominating. The same compounds were identified in queens of a species from Rio Grande, but in this species no alkaloids were detected in worker extracts. Workers of a Diplorhoptrum species collected on Mona Island produced primarily a trans-2-methyl-6-(Z-4-nonenyl)piperidine, 3, with smaller amounts of the cis isomer, whereas the major compound found in the queens of the same species on Mona Island was (5Z,9Z)-3-hexyl-5-methylindolizidine, identical with the alkaloid produced by queens of a species collected on Cabo Rojo. Surprisingly, workers of the Cabo Rojo species produced (5Z,9Z)- and (5E,9E)-3-butyl-5-propylindolizidine (4 and 5, respectively) reported earlier as the 223AB indolizidines from skins of dendrobatid frogs. The possible significance of the qualitative and quantitative differences in the venom alkaloids synthesized by queens and workers is discussed as is the possibility that ants containing such alkaloids may serve as a dietary source for the skin alkaloids used by certain frogs in chemical defense. C1 US FOREST SERV,INT INST TROP FORESTRY,RIO PIEDRAS,PR 00928. UNIV PUERTO RICO,DEPT BIOL,SAN JUAN,PR 00931. NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV GEORGIA,DEPT ENTOMOL,ATHENS,GA 30602. LOS ANGELES CTY MUSEUM NAT HIST,LOS ANGELES,CA 90007. RP Jones, TH (reprint author), VIRGINIA MIL INST,DEPT CHEM,LEXINGTON,VA 24450, USA. NR 41 TC 31 Z9 31 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD JUL PY 1996 VL 22 IS 7 BP 1221 EP 1236 DI 10.1007/BF02266962 PG 16 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA VD011 UT WOS:A1996VD01100002 PM 24226081 ER PT J AU Milne, GWA Wang, SM Nicklaus, MC AF Milne, GWA Wang, SM Nicklaus, MC TI Molecular modeling in the discovery of drug leads SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article; Proceedings Paper CT 11th ICCCRE Meeting CY JUL 17-21, 1995 CL PARIS, FRANCE ID PROTEIN-KINASE-C; GENERATED CHEMICAL STRUCTURES; PHORBOL ESTER PHARMACOPHORE; RAY CRYSTALLOGRAPHIC DATA; INFORMATION-SYSTEM; CAMBRIDGE; AGONISTS; BINDING; COMPLEX; MODULE AB The National Cancer Institute of the U.S.A. maintains a repository of about 500 000 chemicals which it has tested at some time for anticancer activity. As new chemotherapeutic targets present themselves, methods have been developed by which this large database can be re-examined without resorting to expensive high-volume biological screening. Electronic screening, the method described in this paper, begins with the identification of a target enzyme. The pharmacophore used by the enzyme in binding to substrates is identified, and then all compounds in the database that contain the pharmacophore are found. These compounds are then further filtered, for example, by physical properties such as solubility, and the relatively small number of compounds that survive are submitted for biological testing. This use of a primary electronic screen in the search for ligands of protein kinase C is described. The screen is very fast, and the method is quite generally applicable to different enzymes. RP Milne, GWA (reprint author), NCI,DIV MED CHEM,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. RI Nicklaus, Marc/N-4183-2014 NR 27 TC 8 Z9 8 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 1996 VL 36 IS 4 BP 726 EP 730 DI 10.1021/ci9500849 PG 5 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA VA568 UT WOS:A1996VA56800016 PM 8768766 ER PT J AU Spiegel, AM AF Spiegel, AM TI Mutations in G proteins and G protein-coupled receptors in endocrine disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; STIMULATORY G-PROTEIN; CA2+-SENSING RECEPTOR; THYROTROPIN RECEPTOR; ACTIVATING MUTATIONS; PITUITARY-TUMORS; GENE; ONCOGENES RP Spiegel, AM (reprint author), NIDDK, METAB DIS BRANCH, NIH, 10-9N-222, BETHESDA, MD 20892 USA. NR 71 TC 111 Z9 113 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1996 VL 81 IS 7 BP 2434 EP 2442 DI 10.1210/jc.81.7.2434 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UW842 UT WOS:A1996UW84200006 PM 8675557 ER PT J AU Adesanya, OO Zhou, J Bondy, CA AF Adesanya, OO Zhou, J Bondy, CA TI Cellular localization and sex steroid regulation of insulin-like growth factor binding protein messenger ribonucleic acids in the primate myometrium. SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID I IGF-I; ENDOMETRIAL STROMAL CELLS; GENE-EXPRESSION; RECEPTOR GENE; RAT UTERUS; ESTROGEN; SECRETION; PROLIFERATION; PROGESTERONE; FIBROIDS AB Insulin-like growth factors (IGF)-I and -II are abundant in the primate myometrium and are implicated in the sex steroid-induced growth of this tissue. To evaluate the potential for modulation of IGF action in the primate myometrium by locally produced IGF binding proteins (IGFBPs), we examined the cellular localization and sex steroid regulation of IGFBPs 1-5 in the nonhuman primate uterus. Ovariectomized rhesus monkeys were treated with placebo, estradiol (E(2)), or E(2) and progesterone (P-4) (E(2) and P-4) for 2 weeks, after which their uteri were removed and cut into thin serial sections for analysis by in situ hybridization. IGFBP-1 messenger RNA (mRNA) was not detected in control or E(2)-treated uteri but was found in a few unidentified cells in the E(2) and P-4-treated group. IGFBP-2, -3, -4, and -5 mRNAs were all expressed by myometrial smooth muscle cells but each displayed distinctive patterns of regulation by sex steroids. IGFBP-2 was barely detectable in control myometrium, was significantly increased by E, and even more significantly by E(2) and P-4. IGFBP-4 and 5 mRNAs were readily detectable in control myometrium and significantly increased by E(2) treatment. The addition of P-4 to E(2) treatment did not produce a significantly greater augmentation in IGFBP-4 or 5 mRNA level compared with E(2) alone. IGFBP-3 mRNA was abundant in the control myometrium, but in contrast to other IGFBPs was significantly reduced by approximately 75% in smooth muscle cells by E(2) and by E(2) and P-4 treatment. Interestingly, however, IGFBP-3 mRNA was increased in the uterine vascular endothelium by E(2) and by E(2) and P-4 treatment. In summary, this study has shown that four of the six known IGFBPs are highly expressed in the primate myometrium, and that their expression is differentially regulated by sex steroids. The cellular and sex steroid-regulated pattern of IGFBP-2 gene expression is very similar to that of IGF-I, as previously determined in these same myometrial samples. Both IGF I and IGFBP-2 are dependent on E(2) for significant myometrial expression, and both are further augmented by the addition of P-4 to E(2) treatment. Uterine smooth muscle IGFBP-3 mRNA levels are negatively regulated, whereas IGFBP-4 and -5 mRNA levels are positively regulated by E(2); none of these myometrial IGFBPs appears sensitive to the effects of P-4. The present observations, together with our previous data from the same animals, demonstrate that the primate myometrial smooth muscle cell expresses mRNAs for IGF-I and -II, IGF-I and -II receptors, as well as expresses mRNAs for IGFBP-2, -3, -4, and -5. These data provide evidence for complex local interactions between IGF system components regulated by estrogen and progesterone. RP Adesanya, OO (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NATL INST HLTH,10 CTR DR, MSC 1862,BLDG 10, ROOM 10N 262, BETHESDA, MD 20892 USA. NR 36 TC 15 Z9 15 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1996 VL 81 IS 7 BP 2495 EP 2501 DI 10.1210/jc.81.7.2495 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UW842 UT WOS:A1996UW84200015 PM 8675566 ER PT J AU Sorlie, PD Cooper, L Schreiner, PJ Rosamond, W Szklo, M AF Sorlie, PD Cooper, L Schreiner, PJ Rosamond, W Szklo, M TI Repeatability and validity of the rose questionnaire for angina pectoris in the atherosclerosis risk in communities study SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE angina pectoris; validation; repeatability; atherosclerosis ID LIPOPROTEIN CHOLESTEROL; WOMEN; MEN; PREVALENCE; DISEASE; PLASMA AB Angina pectoris (AP) as determined by the Rose questionnaire was assessed in nearly 16,000 black and white men and women participating in the Atherosclerosis Risk in Communities Study, a population study of cardiovascular disease in four communities. The questionnaire was administered at yearly intervals and estimates of repeatability were made. Validity was assessed indirectly by comparing Rose AP to risk factors, prevalent heart disease, medication use, and thickness of carotid artery walls as measured by B-mode ultrasound. Using kappa statistics for agreement of positive Rose AP determinations taken 1 year apart, white men show a higher level of agreement than white women (average kappa 0.36 for white men, 0.30 for white women), and whites show a higher level of agreement than blacks (average kappa 0.23 and 0.22 for black men and women, respectively), Rose AP that persists for more than one determination is associated with thicker carotid artery walls, greater amounts of cigarette smoking, greater prevalence of reported heart attack, and greater use of chest pain medications. A single determination of severe Rose AP is also associated with thicker carotid artery walls. These data suggest that multiple reports and the more severe grading of Rose AP (pain reported while walking on the level) are likely to indicate more severe disease; however, a single report using the Rose questionnaire appears valid, i.e., moderately associated with disease and risk factors, and appropriate for use in epidemiological studies. C1 UNIV N CAROLINA,SCH PUBL HLTH,CHAPEL HILL,NC 27514. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. RP Sorlie, PD (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,NIH,FED BLDG,ROOM 3A10,BETHESDA,MD 20889, USA. FU NHLBI NIH HHS [N01-HC55015, N01-HC55016, N01-HC55018] NR 27 TC 53 Z9 53 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 1996 VL 49 IS 7 BP 719 EP 725 DI 10.1016/0895-4356(96)00022-4 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VA007 UT WOS:A1996VA00700003 PM 8691220 ER PT J AU Mittleman, BB Morse, HC Payne, SM Shearer, GM Mozes, E AF Mittleman, BB Morse, HC Payne, SM Shearer, GM Mozes, E TI Amelioration of experimental systemic lupus erythematosus (SLE) by retrovirus infection SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE systemic lupus erythematosus; murine AIDS; autoantibodies; immune complex deposits ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MICE; DISEASE; INDUCTION; IDIOTYPE; ANTIGENS; VIRUSES AB Experimental SLE can be induced in susceptible 129/J mice by immunization with a human anti-DNA antibody bearing a common idiotype designated 16/6 Id. Immunized mice develop autoantibodies, leukopenia, proteinuria, and immune complex deposits in renal glomeruli. Case reports have described clinical improvement in SLE in individuals becoming infected with HIV-1. Because 129/J mice are susceptible to experimental SLE and to infection with the BM5def murine leukemia virus (MuLV) mixture but do not develop the lymphoproliferative/immunodeficiency disorder known as murine AIDS (MAIDS), we superimposed this infection on immunization with the 16/6 Id. Multiple effects were observed. First, we noted an amelioration in the course of experimental SLE. Second, both in experimental SLE and in BM5def MuLV infection, immunoreactivity to HIV-1 gp 120 was demonstrated, although gp120 is not present in the BM5def MuLV viruses. Third, production of autoantibodies characteristically found in SLE, e.g., anti-DNA, anti-RNP, and anti-SSA, was seen in BM5def MuLV-infected mice, demonstrating that an immune response as a consequence of infection had occurred despite the absence of MAIDS induction. We conclude that (1) retrovirus inoculation may ameliorate the course of experimental SLE; and (2) retrovirus inoculation, even in the absence of MAIDS induction, induces an immunologic response which promotes the production of potentially pathogenic autoantibodies. C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20893. WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP Mittleman, BB (reprint author), NCI,NIH,EIB,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 15 TC 9 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 1996 VL 16 IS 4 BP 230 EP 236 DI 10.1007/BF01541229 PG 7 WC Immunology SC Immunology GA VA015 UT WOS:A1996VA01500007 PM 8840225 ER PT J AU Carethers, JM Hawn, MT Chauhan, DP Luce, MC Marra, G Koi, M Boland, CR AF Carethers, JM Hawn, MT Chauhan, DP Luce, MC Marra, G Koi, M Boland, CR TI Competency in mismatch repair prohibits clonal expansion of cancer cells treated with N-methyl-N'-nitro-N-nitrosoguanidine SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DNA repair; cell cycle; hMLH1; cell death; alkylation damage ID METHYLATING AGENTS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ALKYLATING-AGENTS; DNA; LINE; RESISTANCE; DEFICIENT; DAMAGE; METHYLNITROSOUREA; PROFICIENT AB The phenomenon of alkylaton tolerance has been observed in cells that are deficient in some component of the DNA mismatch repair (MMR) system. An alkylation-induced cell cycle arrest had been reported previously in one MMR-proficient cell line, whereas a MMR-defective clone derived from this line escapes from this arrest. We examined human cancer cell lines to determine if the cell cycle arrest were dependent upon the MMR system, Growth characteristics and cell cycle analysis after MNNG treatment were ascertained in seven MMR-deficient and proficient cell lines, with and without confirmed mutations in hMLH1 or hMSH2 by an in vitro transcription/translation assay. MMR-proficient cells underwent growth arrest in the G2 phase of the cell cycle after the first S phase, whereas MMR-deficient cells escaped an initial G2 delay and resumed a normal growth pattern. In the HCT116 line corrected for defective MMR by chromosome 3 transfer, the G2 phase arrest lasted more than five days. In another MMR-proficient colon cancer cell line, SW480, cell death occurred five days after MNNG treatment. A competent MMR system appears to be necessary for G2 arrest or cell death after alkylation damage, and this cell cycle checkpoint may allow the cell to repair damaged DNA, or prevent the replication of mutated DNA by prohibiting clonal expansion. C1 UNIV CALIF SAN DIEGO,DEPT MED,DIV GASTROENTEROL,SAN DIEGO,CA 92093. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48109. ROCHE BIOMED LABS,RES TRIANGLE PK,NC 27709. NATL INST ENVIRONM HLTH SCI,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 FU NCI NIH HHS [R01 CA39233, R25 CA57716]; NIDDK NIH HHS [K08 DK002433, K08 DK002433-05, K08 DK02433] NR 43 TC 110 Z9 111 U1 0 U2 2 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 JUL 1 PY 1996 VL 98 IS 1 BP 199 EP 206 DI 10.1172/JCI118767 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UW362 UT WOS:A1996UW36200028 PM 8690794 ER PT J AU Shafer, RW Winters, MA Mayers, DL Japour, AJ Kuritzkes, DR Weislow, OS White, F Erice, A Sannerud, KJ Iversen, A Pena, F Dimitrov, D Frenkel, LM Reichelderfer, PS AF Shafer, RW Winters, MA Mayers, DL Japour, AJ Kuritzkes, DR Weislow, OS White, F Erice, A Sannerud, KJ Iversen, A Pena, F Dimitrov, D Frenkel, LM Reichelderfer, PS TI Interlaboratory comparison of sequence-specific PCR and ligase detection reaction to detect a human immunodeficiency virus type 1 drug resistance mutation SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ZIDOVUDINE RESISTANCE; REVERSE-TRANSCRIPTASE AB Sequence-specific PCR was used in six laboratories and a ligase detection reaction was used in one laboratory to detect the zidovudine-resistance mutation at codon 215 of human immunodeficiency virus type 1 (HIV-I) reverse transcriptase DNA. The genotypes of 27 different clinical samples, including cultured HIV-1 isolates, peripheral blood mononuclear cells, and plasma, were correctly identified by 140 of 154 (91%) assays. The sensitivity for detecting a mutation was 96% for HIV-1 reverse transcriptase DNA clone mixtures containing 30% mutant DNA and 62% for mixtures containing 6% mutant DNA. C1 NIAID,DIV AIDS,NIH,DDSCB,BETHESDA,MD 20892. STANFORD UNIV,STANFORD,CA 94305. WALTER REED ARMY INST RES,ROCKVILLE,MD. UNIV COLORADO,DENVER,CO 80202. BETH ISRAEL HOSP,BOSTON,MA 02215. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV MIAMI,MIAMI,FL 33152. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV WASHINGTON,SEATTLE,WA 98195. NR 21 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1996 VL 34 IS 7 BP 1849 EP 1853 PG 5 WC Microbiology SC Microbiology GA UR416 UT WOS:A1996UR41600058 PM 8784610 ER PT J AU Roselli, M Guadagni, F Buonomo, O Belardi, A Vittorini, V MarianiCostantini, R Greiner, JW Casciani, CU Schlom, J AF Roselli, M Guadagni, F Buonomo, O Belardi, A Vittorini, V MarianiCostantini, R Greiner, JW Casciani, CU Schlom, J TI Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY B72.3; GAMMA-INTERFERON; COLON-CARCINOMA; HUMAN-BREAST; CELL-LINES; RADIOLABELED ANTIBODIES; COLORECTAL-CANCER; ENHANCEMENT; TISSUES; LOCALIZATION AB Purpose: The ability of interferons (IFNs) to enhance tumor-associated antigen expression may be an important approach to enhance the efficacy of some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or therapy, The present study was designed to determine whether systemic IFN alpha-2a administration (via the intramuscular [IM] route) could upregulate the expression of tumor-associated glycoprotein-72 (TAG-72) and/or carcinoembryonic antigen (CEA) at histologically confirmed sites of carcinoma, Patients and Methods: Eighteen patients diagnosed with gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to four dose schedules. In cohorts I and II, patients received two injections of 3 or 6 x 10(6) U IFN alpha-2a. per injection, respectively, Patients in cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6) U, respectively, but three injections were given. Tumor and normal colonic mucosa biopsies were obtained from each patient by endoscopy before IFN alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA expression were measured by (1) immunohistochemistry and reported as percent antigen-positive tumor cells, as well as the relative staining intensity, and (2) a quantitative radioimmunoassay. Results: TAG-72 and CEA levels were consistently increased in tumor biopsies taken from patients in cohorts III and IV. For example, of 10 patients treated in cohorts III and IV, eight had enhanced TAG-72 expression when measured either as percentage TAG-72-positive tumor cells or as an increased MAb staining intensity following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10 patients in cohorts III and IV was also elevated following IFN gamma-2a treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies confirmed higher tumor antigen levels following IFN alpha-2a administration. No such increases in TAG-72 or CEA levels were observed in tumor samples taken from patients in cohorts I and II, CEA or TAG-72 expression in samples of histologically confirmed normal colonic mucosa showed little or no change after IFN alpha-2a treatment. Conclusion: Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA expression at distal tumor sites, which may play an important role in immunodiagnosis and therapy. C1 NCI,NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,DEPT SURG,CLIN SURG SECT,ROME,ITALY. REGINA ELENA INST CANC RES,CLIN PATHOL LAB,ROME,ITALY. UNIV CHIETI GABRIELE DANNUNZIO,INST HUMAN PATHOL,CHIETI,ITALY. RI Buonomo, Oreste Claudio/J-4280-2012; Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 NR 46 TC 36 Z9 36 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1996 VL 14 IS 7 BP 2031 EP 2042 PG 12 WC Oncology SC Oncology GA UV715 UT WOS:A1996UV71500008 PM 8683233 ER PT J AU Cameron, BA Perry, SF Wu, C Ko, K Tufts, BL AF Cameron, BA Perry, SF Wu, C Ko, K Tufts, BL TI Bicarbonate permeability and immunological evidence for an anion exchanger-like protein in the red blood cells of the sea lamprey, Petromyzon marinus SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE anion movements; chloride/bicarbonate exchange; red cell proteins; AE1 or band 3; Petromyzon marinus ID ERYTHROCYTE-MEMBRANE; BAND-3 PROTEIN; CO2 TRANSPORT; CHLORIDE TRANSPORT; TROUT; POLYPEPTIDE; DETERGENT; ISOZYMES; BINDING; PLASMA AB Physiological and immune-blotting experiments were used to determine whether the red blood cell membrane of a primitive vertebrate, the sea lamprey Petromyzon marinus, contained a counterpart similar to the vertebrate anion exchange protein known as AE1 or band 3. Results of the physiological experiments which measured CO2 production after adding (HCO3-)-C-14 to the extracellular saline, indicated significant transmembrane bicarbonate movement in lamprey blood which unlike that in most vertebrates, was insensitive to inhibition by 4,4' diisothiocyanatostilbene-2,2' disulfonic acid. The present study also showed that lamprey red blood cells possess acetazolamide-sensitive carbonic anhydrase which is an important component of CO2 production by vertebrate red blood cells. Polyclonal immunoglobulins against a 12 amino acid domain in the C-terminus of the mouse AE1 recognized a trout red blood cell membrane protein with a relative molecular mass of 97 kDa, but failed to immunoreact with any membrane proteins from the red blood cells of lamprey. Antibodies against trout AE1 immunoreacted with trout red blood cell membrane proteins of approximately 97 kDa, 200 kDa and > 200 kDa. Interestingly, only a 200-kDa membrane protein from the red blood cells of the primitive lamprey immunoreacted with the trout anti-AE1 immunoglobulin proteins. Therefore, lamprey red blood cells appear to possess an AE1-like protein that may be physiologically different than that in most other vertebrates. C1 QUEENS UNIV,DEPT BIOL,KINGSTON,ON K7L 3N6,CANADA. UNIV OTTAWA,DEPT BIOL,OTTAWA,ON K1N 6N5,CANADA. NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 34 TC 15 Z9 16 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0174-1578 J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD JUL PY 1996 VL 166 IS 3 BP 197 EP 204 DI 10.1007/BF00263983 PG 8 WC Physiology; Zoology SC Physiology; Zoology GA VA210 UT WOS:A1996VA21000006 PM 8765665 ER PT J AU Lambert, CG Darden, TA Board, JA AF Lambert, CG Darden, TA Board, JA TI A multipole-based algorithm for efficient calculation of forces and potentials in macroscopic periodic assemblies of particles SO JOURNAL OF COMPUTATIONAL PHYSICS LA English DT Article ID RANGE ELECTROSTATIC INTERACTIONS; MOLECULAR-DYNAMICS; 3 DIMENSIONS; EWALD SUMS; SIMULATIONS; CRYSTALS; WATER AB A new and efficient algorithm based on multipole techniques is presented which calculates the electrostatic forces and potentials in macroscopic periodic assemblies of particles, The fast multipole algorithm (FMA) can be used to compute forces within the n-particle unit cell in O(n) time. For the cubic lattice, forces due to a 3(k) x 3(k) x 3(k) lattice of images of the unit cell, containing 3(3k) n particles, can be computed in O(nk(2) + k(3) log k) time to arbitrary precision. The algorithm was readily added onto an existing FMA implementation, and computational results are presented. Accurate electrostatic computations were done on a 3(8) x 3(8) x 3(8) region of 100000-particle unit cells, giving a volume of 28 quadrillion particles at less than a twofold cost over computing the forces and potentials in the unit cell alone. In practice, a k = 4 ... 6 simulation approximates the true infinite lattice Ewald sum forces (including the shape-dependent dipole correction) to high accuracy, taking 25-30 % more time to compute than only the unit cell. The method extends to noncubic unit cell shapes, and noncubic macroscopic shapes. Simple code modifications allowed computation of forces within macroscopic spheres and ellipsoids, and within near-infinite square, circular, and elliptical surfaces formed of unit cubes replicated along Two of the three axes. In addition to efficient periodic simulations, the method provides a powerful tool to study limiting behavior of various finite crystal shapes, as well as surface phenomena in molecular dynamics simulations. (C) 1996 Academic Press, Inc. C1 NIEHS,RES TRIANGLE PK,NC 27709. DUKE UNIV,DEPT ELECT ENGN,DURHAM,NC 27708. RP Lambert, CG (reprint author), DUKE UNIV,DEPT COMP SCI,DURHAM,NC 27708, USA. NR 22 TC 57 Z9 57 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 0021-9991 J9 J COMPUT PHYS JI J. Comput. Phys. PD JUL PY 1996 VL 126 IS 2 BP 274 EP 285 DI 10.1006/jcph.1996.0137 PG 12 WC Computer Science, Interdisciplinary Applications; Physics, Mathematical SC Computer Science; Physics GA UW363 UT WOS:A1996UW36300003 ER PT J AU Utsuki, T Brem, H Pitha, J Loftsson, T Kristmundsdottir, T Tyler, BM Olivi, A AF Utsuki, T Brem, H Pitha, J Loftsson, T Kristmundsdottir, T Tyler, BM Olivi, A TI Potentiation of anticancer effects of microencapsulated carboplatin by hydroxypropyl alpha-cyclodextrin SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE carboplatin; hydroxypropyl cyclodextrins; microcapsules; sustained release; interstitial chemotherapy; cancer ID BETA-CYCLODEXTRIN; COMPETING AGENT; DRUG CARRIER; DERIVATIVES; COMPLEXES; CISPLATIN; BIOAVAILABILITY; PHENYLALANINE; ENHANCEMENT; CINNARIZINE AB Cyclodextrins are cyclic oligosaccharides that can change physicochemical properties of drugs by forming inclusion complexes with them. These changes may enhance the therapeutic potential of drugs by diminishing their decomposition before they enter tissues and by altering how they enter tissue. Carboplatin is an anticancer drug that is active against brain tumors and has recently been tested as a potential agent for interstitial chemotherapy. To test whether complex formulation with cyclodextrins would improve interstitial treatment with carboplatin, we studied the efficacy of carboplatin-cyclodextrin complexes, free and encapsulated, in an experimental rat glioma model. Carboplatin hydroxypropyl alpha-cyclodextrin complexes were incorporated into ethylcellulose microcapsules at a 2.2% w/w loading. We found that carboplatin was released from these microcapsules in a sustained manner for at least 110 days in vitro, that the rate was faster than that of encapsulated carboplatin alone, and that hydroxypropyl alpha-cyclodextrin protected the carboplatin from degradation. Further, the complex was more effective than carboplatin alone when tested on monolayers of F98 glioma cells. For testing the efficacy of the carboplatin-hydroxypropyl cyclodextrin complex in the rat glioma model, 56 Fischer rats were injected in the left hemisphere with F98 glioma cells. Five days later the rats were randomly divided into seven groups. Median survival of the first control group receiving no treatment was 20 days. The second group receiving an intratumoral injection of carboplatin had a median survival of 1 day, indicating severe cytotoxicity. The third group receiving systemic carboplatin had a median survival of 34 days. Median survival of the fourth group which received empty microcapsules was 24 days. The fifth group, treated with microcapsules loaded with hydroxypropyl alpha-cyclodextrin alone, showed a median survival of 20 days. The sixth group, treated with microcapsules loaded with carboplatin alone, showed a median survival of 34 days. The seventh group, treated with microcapsules loaded with carboplatin-hydroxypropyl alpha-cyclodextrin complex, showed a median survival of 51 days. This experiment demonstrated that the microencapsulated carboplatin-hydroxypropyl alpha-cyclodextrin complex is more effective than the nonencapsulated carboplatin. This study also shows that interstitial delivery of carboplatin-hydroxypropyl cyclodextrin complexes from a microencapsulated formulation is effective against experimental brain tumors. C1 NIA,NIH,CTR GERONTOL RES,BALTIMORE,MD 21224. UNIV ICELAND,DEPT PHARM,IS-127 REYKJAVIK,ICELAND. RP Utsuki, T (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSURG,725 N WOLFE ST,HUNTERIAN 817,BALTIMORE,MD 21205, USA. RI Loftsson, Thorsteinn/N-3438-2013; Olivi, Alessandro/K-6531-2016; OI Olivi, Alessandro/0000-0002-4489-7564; Loftsson, Thorsteinn/0000-0002-9439-1553 NR 34 TC 33 Z9 33 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JUL PY 1996 VL 40 IS 3 BP 251 EP 260 DI 10.1016/0168-3659(95)00192-1 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA UY471 UT WOS:A1996UY47100011 ER PT J AU Liao, DP Evans, GW Chambless, LE Barnes, RW Sorlie, P Simpson, RJ Heiss, G AF Liao, DP Evans, GW Chambless, LE Barnes, RW Sorlie, P Simpson, RJ Heiss, G TI Population-based study of heart rate variability and prevalent myocardial infarction - The atherosclerosis risk in communities study SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE myocardial infarction; heart rate variability; race; beta-blocker; population-based study ID CORONARY-ARTERY DISEASE; RATE SPECTRAL-ANALYSIS; SYMPATHOVAGAL INTERACTION; MORTALITY; QUESTIONNAIRE AB Clinically based studies have indicated that patients who have suffered myocardial infarction (MI) exhibit lower heart rate variability (HRV). Such associations have not been reported at the population level. To investigate whether MI is related to lower HRV in the general population, the authors examined a stratified random sample of 2,243 men and women aged 45-63 years, of whom 260 had had MI and 1,983 were free of any coronary heart disease manifestations. All were part of the biracial cohort of the Atherosclerosis Risk in Communities study sampled from four United States communities. Resting, 2-minute supine heart rate data were analyzed using spectral analysis to estimate high-frequency (0.16-0.35 Hz) and low-frequency (0.025-0.15 Hz) spectral powers as conventional indices of HRV. The mean levels of high-frequency powers were 1.02 and 1.23 (beats/min)(2) for MI and non-MI groups, respectively (P < .05), and the low-frequency means were 2.40 and 3.11 (beats/min)(2) for MI and non-MI groups, respectively (P < .01). Age, race, and sex-adjusted odds ratios (95% confidence interval) of lower high-frequency and low-frequency powers contrasting MI to non-MI individuals were 1.52 (range, 1.09-2.10) and 1.54 (range, 1.12-2.10), respectively. After adjustment for use of beta-blocker medication, the odds ratios (95% confidence interval) were 1.26 (range, 0.88-1.81) and 1.22 (range, 0.87-1.69) for lower high-frequency and low-frequency powers, respectively. The findings from this first population-based study of prevalent MI and HRV provide support for an inverse association between MI and lower HRV. However, adjusting for beta-blocker use eliminates the statistical association. These findings confirm that impaired HRV is found in individuals with prevalent MI, even when drawn as a sample of community-dwelling individuals. This impaired HRV may contribute to the increased risk of subsequent cardiovascular events previously observed in survivors of acute MI. The cross-sectional data also suggest that use of beta-blockers diminishes the odds of lower HRV associated with MI. C1 UNIV N CAROLINA, SCH PUBL HLTH, DEPT BIOSTAT, CHAPEL HILL, NC 27514 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, WINSTON SALEM, NC 27103 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT NEUROL, WINSTON SALEM, NC 27103 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, NIH, BETHESDA, MD 20892 USA. 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-55016, N01-HC-55015] NR 35 TC 14 Z9 14 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD JUL PY 1996 VL 29 IS 3 BP 189 EP 198 DI 10.1016/S0022-0736(96)80082-3 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VB425 UT WOS:A1996VB42500005 PM 8854330 ER PT J AU Chen, YD Dougherty, ER AF Chen, YD Dougherty, ER TI Adaptive reconstructive tau-openings: Convergence and the steady-state distribution SO JOURNAL OF ELECTRONIC IMAGING LA English DT Article ID DIGITAL MORPHOLOGICAL FILTERS; CONDITIONAL-EXPECTATION; BINARY FILTERS; REPRESENTATION; SIGNAL AB A parameterized tau-opening is a filter defined as a union of openings by a collection of compact convex structuring elements, each scalar multiplied by the parameter. For a reconstructive tau-opening, the filter is modified by fully passing any connected component not completely eliminated Applied to the signal-union-noise model. in which the reconstructive filter is designed to sieve out clutter while passing the signal, the optimization problem is to find a parameter value that minimizes the MAE between the filtered and ideal image processes. The present study introduces an adaptation procedure for the design of reconstructive tau-openings. The adaptive filter fits into the framework of Markov processes, the adaptive parameter being the state of the process. There exists a stationary distribution governing the parameter in the steady state and convergence is characterized via the steady-state distribution. Key filter properties such as parameter mean, parameter variance, and expected error in the steady state are characterized via the stationary distribution. The Chapman-Kolmogorov equations are developed for various scanning modes and transient behavior is examined. (C) 1996 SPIE and IS&T. C1 TEXAS A&M UNIV,CTR APPL TECHNOL,COLLEGE STN,TX 77843. TEXAS A&M UNIV,DEPT ELECT ENGN,COLLEGE STN,TX 77843. RP Chen, YD (reprint author), NATL CTR HUMAN GENOME RES,NIH,BETHESDA,MD 20892, USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU I S & T - SOC IMAGING SCIENCE TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 SN 1017-9909 J9 J ELECTRON IMAGING JI J. Electron. Imaging PD JUL PY 1996 VL 5 IS 3 BP 266 EP 282 DI 10.1117/12.244908 PG 17 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA WL795 UT WOS:A1996WL79500003 ER PT J AU Schwartz, RH AF Schwartz, RH TI Models of T cell anergy: Is there a common molecular mechanism? SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID ANTIGEN-PRESENTING CELLS; CLONAL ANERGY; LYMPHOCYTES-T; INDUCTION; PROLIFERATION; TOLERANCE; RECEPTOR; IL-10; CD28; STIMULATION RP Schwartz, RH (reprint author), NIH,CELLULAR & MOLEC IMMUNOL LAB,BLDG 4,RM 111,BETHESDA,MD 20892, USA. NR 70 TC 417 Z9 427 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1996 VL 184 IS 1 BP 1 EP 8 DI 10.1084/jem.184.1.1 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UW677 UT WOS:A1996UW67700001 PM 8691122 ER PT J AU Zhang, J Berenstein, EH Evans, RL Siraganian, RP AF Zhang, J Berenstein, EH Evans, RL Siraganian, RP TI Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SIGNAL-TRANSDUCTION; MAST-CELLS; PHOSPHOLIPASE C-GAMMA-1; MONOCLONAL-ANTIBODIES; HISTAMINE-RELEASE; PHOSPHORYLATION; ACTIVATION; ASSOCIATION; AGGREGATION; ENGAGEMENT AB Aggregation of the high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells results in rapid tyrosine phosphorylation and activation of Syk, a cytoplasmic protein tyrosine kinase. To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant of RBL-2H3 cells that has no detectable Syk by immunoblotting and by in vitro kinase reactions. In these Syk-deficient TB1A2 cells, aggregation of Fc epsilon RI induced no histamine release and no detectable increase in total cellular protein tyrosine phosphorylation. However, stimulation of these cells with the calcium ionophore did induce degranulation. Fc epsilon RI aggregation induced tyrosine phosphorylation of the beta and gamma subunits of the receptor, but no increase in the tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2 and no detectable increase in intracellular free Ca2+ concentration. By transfection, cloned lines were established with stable expression of Syk. In these reconstituted cells, Fc epsilon RI aggregation induced tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2, an increase in intracellular free Ca2+ and histamine release. These results demonstrate that Syk plays a critical role in the early Fc epsilon RI-mediated signing events. It further demonstrates that Syk activation occurs downstream of receptor phosphorylation, but upstream of most of the Fc epsilon RI-mediated protein tyrosine phosphorylations. C1 NIDR,NIH,IMMUNOL LAB,BETHESDA,MD 20892. NIDR,NIH,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 43 TC 212 Z9 214 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1996 VL 184 IS 1 BP 71 EP 79 DI 10.1084/jem.184.1.71 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UW677 UT WOS:A1996UW67700008 PM 8691151 ER PT J AU Denkers, EY SchartonKersten, T Barbieri, S Caspar, P Sher, A AF Denkers, EY SchartonKersten, T Barbieri, S Caspar, P Sher, A TI A role for CD4(+)NK1.1(+)T T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD8(+) effector function against intracellular infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; TOXOPLASMA-GONDII; CEREBRAL TOXOPLASMOSIS; CHORIOMENINGITIS VIRUS; MICE; CD4+; GAMMA; RESISTANCE; PARASITE; ENCEPHALITIS AB Major histocompatibility complex (MHC) class II (A beta) knockout mice were vaccinated with ts-4, an attenuated mutant strain of Toxoplasma gondii, which ill normal animals induces strong T cell immunity mediated by interferon gamma (IFN-gamma). After challenge with the lethal parasite strain RH, the knockout mice displayed decreased resistance consistent with absence of CD4(+) effecters. Nevertheless, these animals generated. CD8(+) lymphocyte effectors capable of mediating partial protection through IFN-gamma secretion. Morever, in vivo neutralization experiments indicated that the development of resistance in knockout mice depends on CD4(+) cells as well as interleukin 2 (IL-2). The identity of the IL-2-producing protective cell population was further characterized as CD4(+), NK1.1(+) by in vitro depletion studies and reverse transcriptase-PCR analysis of fluorescence-activated cell sorter (FACS)-purified CD4(+)NK1.1(+) T lymphocytes. These results demonstrate that in the absence of conventional MHC class II-restricted CD4(+) T lymphocytes, CD8 printing persists and mediates partial protective immunity to T. gondii. Moreover, the data argue that CD4+, NK1.1(+) cells, previously implicated in the initiation of T helper cell 2 (Th2) responses through their production of IL-4, can also play a role as alternative IL-2-secreting helper cells in Th1-mediated host resistance to infection. C1 NIAID, NIH, IMMUNOBIOL SECT, PARASIT DIS LAB, BETHESDA, MD 20892 USA. NIAID, NIH, BIOL RESOURCES BRANCH, BETHESDA, MD 20892 USA. NR 44 TC 136 Z9 137 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1996 VL 184 IS 1 BP 131 EP 139 DI 10.1084/jem.184.1.131 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UW677 UT WOS:A1996UW67700014 PM 8691126 ER PT J AU Sousa, CRE Levine, EH Germain, RN AF Sousa, CRE Levine, EH Germain, RN TI Partial signaling by CD8(+) T cells in response to antagonist ligands SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN-PRESENTING CELLS; RECEPTOR LIGAND; PEPTIDE; COMPLEX; MOLECULES; BINDING; MHC; PROLIFERATION; SEPARATION; ACTIVATION AB Structural variants of art agonist peptide-major histocompatibility complex (MHC) molecule ligand can show partial agonist and/or antagonist properties. A number of such altered ligands appear to act as pure antagonists. They lack any detectable ability to induce T cell effector function and have been described as unable to induce calcium transients and turnover of inositol phosphates. This has been interpreted as an inability of these ligands to initiate any T cell receptor (TCR)-dependent signal transduction, with their antagonist properties ascribed to competition with offered agonist for TCR occupancy. Yet antagonists for mature CD8(+) T cells can induce positive selection of thymocytes, implying active induction of T cell differentiation events, and partial agonists or agonist/antagonist combinations elicit a distinctive pattern of early TCR-associated tyrosine phosphorylation events in CD4(+) T cells. We have therefore directly examined proximal TCR signaling in a CD8(+) T cell line in response to various related Ligands. TCR engagement with natural peptide-MHC class I agonist resulted in the same pattern of early TCR-associated tyrosine phosphorylation events as seen with CD4(+) cells, including accumulation of both the p21 and p23 forms of phosphorylated zeta, phosphorylation of CD3 epsilon, and association of phosphorylated ZAP-70 with the TCR. Two antagonists that lacked the ability to induce any detectable CTL effector response (cytolysis, esterase release, gamma interferon secretion, interleukin-2 receptor alpha upregulation) were nevertheless found to also induce TCR-dependent phosphorylation events. In these cases, there was preferential accumulation of the p21 form of phospho-zeta: without net phosphorylation of CD3 epsilon, as well as the association of nonphosphorylated ZAP-70 kinase with the receptor. These data show that variant ligands induce similar TCR-dependent phosphorylation events in CD8(+) T cells as first observed in CD4(+) cells. More importantly, they demonstrate that some putatively pure antagonists are actually a subset of partial agonists able to induce intracellular biochemical changes through the TCR. This delivery of a partial signal by antagonists raises the possibility that antagonism in some cases may result from active interference with stimulation of effector activity by agonist in mature T cells, while the same variant signal could selectively trigger intracellular events that allow positive without negative selection in thymocytes. C1 NIAID,NIH,LI,LBS,DIR,BETHESDA,MD 20892. NR 39 TC 60 Z9 60 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1996 VL 184 IS 1 BP 149 EP 157 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UW677 UT WOS:A1996UW67700016 ER PT J AU Shen, XL Hu, B McPhie, P Wu, XH Fox, A Germain, RN Konig, R AF Shen, XL Hu, B McPhie, P Wu, XH Fox, A Germain, RN Konig, R TI Peptides corresponding to CD4-interacting regions of murine MWC class II molecules modulate immune responses of CD4(+) T lymphocytes in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CELL-RECEPTOR; BINDING-SITE; INTERLEUKIN-2 PRODUCTION; CIRCULAR-DICHROISM; ANTIGEN RECEPTOR; ENTEROTOXIN-B; BETA-CHAIN; ACTIVATION; MICE AB Immune responses mediated by CD4(+) T cells depend on Ag-specific alpha beta TCRs that recognize the specific antigenic peptide presented by MHC class II molecules. Interactions between CD4 coreceptors and monomorphic regions of MHC class II molecules contribute to these responses. To examine whether immune reactions could be modulated by specifically interfering with CD4-MHC class II interactions, we have used, in various in vitro and in vivo assays, peptides that correspond to a region of MHC class II molecules previously shown to control interaction with CD4. Depending on the chemical nature and concentration of these peptides, they modulated Ag-specific responses of CD4(+) T cells. At high concentrations, these peptides inhibited T cell responses in vitro. However, under conditions that can cause Ag-induced unresponsiveness, the peptides enhanced T cell responses. Also, primary in vivo immune responses to systemically administered soluble protein Ag, keyhole limpet hemocyanin, were enhanced when mice were treated with peptides corresponding to the CD4-interacting region of MHC class II molecules but not when treated with control peptides. Lymphokine profiles suggested that the peptides may favor the differentiation of Th1 cells, because lymphocytes from peptide-treated mice secreted more IL-2 and IFN-gamma than lymphocytes from nontreated or control-peptide-treated mice upon restimulation with Ag in vitro. These results demonstrate that MHC class II-derived peptides can directly interfere with interactions with CD4 and modulate T cell responses in vitro and in vivo. C1 UNIV TEXAS,MED BRANCH,SEALY CTR MOL SCI,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555. NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Konig, Rolf/B-3128-2008 NR 75 TC 26 Z9 29 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1996 VL 157 IS 1 BP 87 EP 100 PG 14 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900012 PM 8683160 ER PT J AU Yu, CR Lin, JX Fink, DW Akira, S Bloom, ET Yamauchi, A AF Yu, CR Lin, JX Fink, DW Akira, S Bloom, ET Yamauchi, A TI Differential utilization of Janus kinase-signal transducer and activator of transcription signaling pathways in the stimulation of human natural killer cells by IL-2, IL-12, and IFN-alpha SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN NK CELLS; INTERFERON-GAMMA; BETA-CHAIN; MEDIATED CYTOTOXICITY; HUMAN INTERLEUKIN-2; T-CELLS; INDUCTION; RECEPTOR; TYROSINE AB IL-2-, IL-12-, and IFN-alpha-mediated signaling pathways were analyzed in primary NK cells and in the NK3.3 cell line. Gel mobility shift and immunoprecipitation analyses revealed that in addition to activating STAT3 (signal transducer and activator of transcription-3) and STAT5, IL-2 induced tyrosine and serine phosphorylation of STAT1 alpha, which formed IFN-gamma-activated sequence-binding complexes by itself and with STAT3. Although IL-2 and IFN-alpha activated STAT1 alpha and STAT5, IL-2 predominantly activated STAT5, while IFN-alpha predominantly activated STAT1 alpha. IL-2 induced less STAT1 alpha activation and IFN-alpha induced greater STAT5 activation in NK3.3 cells compared with preactivated primary NK cells. In NK3.3 cells, IL-2 induced comparable formation of c-fos promoter sis-inducible element IFN-gamma-activated sequence-binding complexes containing STAT3 alone with complexes containing STAT3 and STAT1 alpha, while in preactivated primary NK cells, it preferentially induced complexes containing STAT3 and STAT1 alpha. Thus, signaling in NK3.3 cells is not always identical with that in primary NK cells. In contrast to IL-2 and IFN-alpha, IL-12 induced strong tyrosine phosphorylation of STAT4 and variable weak phosphorylation of STAT3. However, supershift analyses using the c-fos promoter sis-inducible element probe showed that IL-12 activated STAT4, STAT1 alpha, and STAT3, acid induced complexes containing STAT4 only, STAT4 with STAT1 alpha, STAT3 with STAT1 alpha, or STAT1 alpha only in preactivated primary NK cells. STAT1 alpha activation by IL-12 correlated with increased phosphorylation of serine, but not tyrosine. Finally, IL-2 induced tyrosine phosphorylation of JAK1 and JAK3, while IL-12 induced phosphorylation of JAK2 and TYK2 in both preactivated primary NK and NK3.3 cells. Differential phosphorylation and consequent differential activation of both separate and overlapping STAT proteins by IL-2, IL-12, and IFN-alpha may provide a molecular basis for the similarities and differences in the actions of these cytokines on NK cells. C1 US FDA,CELLULAR IMMUNOL LAB,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. US FDA,CELL BIOL LAB,DIV CYTOKINE BIOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20037. OSAKA UNIV,INST MOLEC & CELLULAR BIOL,DIV IMMUNOL,SUITA,OSAKA 565,JAPAN. NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. RI Akira, Shizuo/C-3134-2009 NR 73 TC 80 Z9 82 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 JUL 1 PY 1996 VL 157 IS 1 BP 126 EP 137 PG 12 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900016 PM 8683106 ER PT J AU Currier, JR Yassai, M Robinson, MA Gorski, J AF Currier, JR Yassai, M Robinson, MA Gorski, J TI Molecular defects in TCRBV genes preclude thymic selection and limit the expressed TCR repertoire SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BETA-CHAIN GENES; ALLELIC EXCLUSION; RECEPTOR; DNA; SPECTRUM; ALPHA AB A prerequisite for the assembly of a functional TCR is the rearrangement of gene segments to result in in-frame transcripts that can vary in length across the CDR3 region. Selection for in-frame 3-bp spaced rearrangements is observed for functional TCRB genes in thymocyte DNA and mRNA transcripts from PBMC. Previous analyses of the expressed human TCRBV gene repertoire have suggested that BV10S1 and BV19S1 gene segments may be expressed at very low levels or not at all in some individuals. CDR3 size analysis for BV10 and BV19 transcripts and thymic DNA rearrangements revealed no such selection of in-frame 3-bp spaced rearrangements. Comparison of the BV19 leader intron sequence with consensus 5'-splice signal sequences suggested that the mature mRNA for this gene would contain the unspliced leader intron. Sequencing of BV19 transcripts from PBMC confirmed that the intron was not spliced, resulting in a predicted translation product that terminates prematurely. Both genomic DNA and mRNA were analyzed for the BV10 gene. The leader sequence contained a single extra base, which would result in a shift in the V region reading frame upon conventional mRNA splicing. This gene is predicted to be nonfunctional due to the presence of a stop codon in the V gene segment just after the splice signal. A splice variant that uses an alternative 3'-splice site further downstream in the V region was also detected. This variant is predicted to be nonfunctional due to the presence of an in-frame stop codon in the V region. These processing defects are sufficient to abrogate positive selection. Therefore, the conclusions drawn from previous studies of the expressed T cell repertoire in normal and disease states based on the presumed functional status of these two genes need to be reassessed. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. BLOOD CTR SE WISCONSIN INC,BLOOD RES INST,IMMUNOGENET RES,MILWAUKEE,WI 53233. FU NHGRI NIH HHS [HG49747] NR 30 TC 26 Z9 26 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 JUL 1 PY 1996 VL 157 IS 1 BP 170 EP 175 PG 6 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900021 PM 8683111 ER PT J AU Parker, CE Papac, DI Trojak, SK Tomer, KB AF Parker, CE Papac, DI Trojak, SK Tomer, KB TI Epitope mapping by mass spectrometry - Determination of an epitope on HIV-1(IIIB) p26 recognized by a monoclonal antibody SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; 3-DIMENSIONAL STRUCTURE; ESCHERICHIA-COLI; PROTEIN ANTIGEN; CORE ANTIGENS; HIV; COMPLEX; GENE; GAG; AIDS AB Matrix-assisted laser desorption mass spectrometry in combination with proteolytic protection assays has been used to identify the functional epitope on HIV-1(IIIB) p26 recognized by a mAb. In this procedure, the intact protein is affinity bound to an immobilized mAb under physiologic conditions. A combination of proteolytic enzymatic cleavages was then performed to remove unprotected residues. Protected residues were identified by matrix-assisted laser desorption mass spectrometry based on their m.w. With this approach, an 11-residue sequence was identified as the most tightly affinity-bound fragment. In addition, two less tightly bound segments were observed. These latter two residues may contain elements of a discontinuous epitope or may be residues involved in a wider contact area. The combination of matrix-assisted laser desorption and proteolytic epitope footprinting has been applied to the determination of the epitope on a recombinant protein recognized by a mAb but should be equally applicable to the definition of an epitope on a native protein in its natural folded conformation. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 36 TC 46 Z9 46 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1996 VL 157 IS 1 BP 198 EP 206 PG 9 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900025 PM 8683115 ER PT J AU Frucht, DM Holland, SM AF Frucht, DM Holland, SM TI Defective monocyte costimulation for IFN-gamma production in familial disseminated Mycobacterium avium complex infection - Abnormal IL-12 regulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; T-CELLS; TUBERCULOSIS; MICE; PURIFICATION; RESISTANCE; CYTOKINE AB We have described previously a family in which several members have disseminated Mycobacterium avium complex infection. PBMC from affected members produced abnormally low amounts of IFN-gamma upon stimulation with PHA. Using PHA-stimulated allogeneic cocultures of highly purified monocytes and T cells from familial patients and normal subjects, we have now demonstrated that familial patient monocytes are defective in accessory cell function for IFN-gamma production. Familial patient monocytes did not inhibit IFN-gamma production by normal cells, nor did inhibition of PG synthesis restore normal IFN-gamma production by familial patient cells. Familial patient cells responded to the addition of exogenous IL-12 by increasing IFN-gamma production, while addition of exogenous anti-IL-12 had an insignificant effect on their IFN-gamma production. IL-12 was undetectable in PHA-stimulated cocultures of familial patient monocytes with familial or normal T cells. In addition, IL-12 production by adherent cells from patients and their unaffected mothers was abnormally low following stimulation with fixed Staphylococcus aureus Cowan I strain. However, normal amounts of IL-12 were detected when adherent familial patient cells were stimulated with S. aureus Cowan I strain and IFN-gamma, suggesting abnormal regulation of IL-12 production by familial monocytes. This is the first report of defective IL-12 production associated with increased susceptibility to an infectious disease, a finding that supports the critical role of this cytokine in host defense. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 35 TC 132 Z9 135 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 JUL 1 PY 1996 VL 157 IS 1 BP 411 EP 416 PG 6 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900053 PM 8683146 ER PT J AU Marincola, FM Rivoltini, L Salgaller, ML Player, T Rosenberg, SA AF Marincola, FM Rivoltini, L Salgaller, ML Player, T Rosenberg, SA TI Differential anti-MART-1/MelanA CTL activity in peripheral blood of HLA-A2 melanoma patients in comparison to healthy donors: Evidence of in vivo priming by tumor cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; immunotherapy; MART-1 ID CYTOLYTIC T-LYMPHOCYTES; INFILTRATING LYMPHOCYTES; IN-VITRO; GENE; INDUCTION; PEPTIDES; TYROSINASE; EXPRESSION; TOLERANCE; IDENTIFICATION AB MART-1 is expressed in both normal and neoplastic cells of melanocytic origin. Peripheral blood mononuclear cells (PBMC) from melanoma patients recognize and lyse tumor cells after repetitive in vitro stimulation with the immunodominant peptide MART-1(27-35). In this study, we compared the characteristics of the cytotoxic T lymphocyte (CTL) response to MART-1 in PBMC from 13 HLA-A2+ melanoma patients with PBMC from 9 normal healthy donors stimulated in vitro with MART-1(27-35) (AAGIGILTV) or FLuM1(58-66) (GILGFVFTL) peptides. The expansion rate among CTLs from different patients was variable and did not correlate with the development of specificity against the MART-1(27-35) or FluM1(58-66) peptides. Specific anti-MART-1(27-35) cytotoxicity could be generated in 13 of 13 melanoma patients but only in 5 of 9 healthy donors (p < 0.001), Anti-FluM1(58-66) activity could be generated in six of seven melanoma patients and six of seven healthy donors. Specific activity against MART-1(27-35), but not FuM1(58-66), was detectable significantly earlier after repetitive in vitro stimulation in melanoma patients (22.7 +/- 2.0 days compared with 32.7 +/- 1.7 days for healthy donors, p < 0.01). This report provides the first evidence of an enhanced level of sensitization of tumor-bearing hosts compared with normal individuals against a differentiation antigen shared by tumor and normal cells of the same lineage. These findings may have important implications for delineating events involved in the biology of tumor rejection naturally or in response to active specific immunotherapy. C1 NCI,SURG BRANCH,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. OI Rivoltini, Licia/0000-0002-2409-6225 NR 38 TC 107 Z9 109 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1996 VL 19 IS 4 BP 266 EP 277 DI 10.1097/00002371-199607000-00003 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA VE270 UT WOS:A1996VE27000003 PM 8877721 ER PT J AU Curti, BD Ochoa, AC Urba, WJ Alvord, WG Kopp, WC Powers, G Hawk, C Creekmore, SP Gause, BL Janik, JE Holmlund, JT Kremers, P Fenton, RG Miller, L Sznol, S Smith, JW Sharfman, WH Longo, DL AF Curti, BD Ochoa, AC Urba, WJ Alvord, WG Kopp, WC Powers, G Hawk, C Creekmore, SP Gause, BL Janik, JE Holmlund, JT Kremers, P Fenton, RG Miller, L Sznol, S Smith, JW Sharfman, WH Longo, DL TI Influence of interleukin-2 regimens on circulating populations of lymphocytes after adoptive transfer of anti-CD3-stimulated T cells: Results from a phase I trial in cancer patients SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE IL-2; lymphocytes; anti-CD3; T cells ID TUMOR-INFILTRATING LYMPHOCYTES; CONTINUOUS-INFUSION INTERLEUKIN-2; ACTIVATED KILLER CELLS; BOLUS INTERLEUKIN-2; METASTATIC MELANOMA; DEATH APOPTOSIS; SOLID TUMORS; ANTI-CD3; ANTIBODY; THERAPY AB The adoptive transfer of anti-CD3-stimulated T killer (T-AK) cells was tested with different bolus and infusional interleukin-2 (IL-2) regimens, and anti-CD3 stimulation procedures to determine immunologic and antitumor effects in patients with a variety of advanced cancers. Indium-111 labeling was used to observe traffic patterns of the infused T-AK. Autologous peripheral blood mononuclear cells were obtained by leukapheresis. Cyclophosphamide (300 mg/m(2)) was given to most patients immediately after leukapheresis, The harvested cells were activated ex vivo with anti-CD3 overnight or for 4 days, at which time cells were reinfused and an IL-2 regimen was begun. Treatment was repeated 28 days later. This treatment regimen induced significant increases in leukocytes, lymphocytes, and eosinophils in patients in most treatment cohorts. Circulating lymphocytes were predominantly CD3(+) T cells with preferential expansion of the CD8(+) subset. Patients receiving cells stimulated in vitro for 4 days had significant T-cell lymphocytosis with either infusional or bolus plus infusional IL-2 regimens. T-cell viability was decreased in culture after a second 4-day stimulation with anti-CD3 at day 28; this decrease could be prevented by adding IL-2 to the culture media. Cells stimulated overnight required both bolus and infusional IL-2 to show an atypical lymphocytosis in vivo. Overnight-stimulated T-AK did not show decreases in in vitro viability at the day 28 restimulation, Indium-111-labeled cells trafficked to the liver, spleen, and bone marrow. No increase in uptake was observed in tumor deposits. There were 2 patients with partial responses, 5 with minor responses, 19 with stable disease, and 88 with progressive disease. The length of in vitro anti-CD3 stimulation, and the dose and timing of IL-2 administration in vivo results in different circulating leukocyte populations after adoptive T-AK infusion. Generally, the CD8(+) T-cell subset was preferentially expanded by this treatment approach. Repeated ex vivo stimulation with anti-CD3 may cause cell death. C1 FREDERICK MEM HOSP,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV,FREDERICK,MD. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP Curti, BD (reprint author), NCI,FREDERICK CANC RES FACIL,BIOL RESPONSE MODIFIERS PROGRAM,501 W 7TH ST,SUITE 3,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 32 TC 17 Z9 19 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1996 VL 19 IS 4 BP 296 EP 308 DI 10.1097/00002371-199607000-00005 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA VE270 UT WOS:A1996VE27000005 PM 8877723 ER PT J AU Lewis, LL Venzon, D Church, J Farley, M Wheeler, S Keller, A Rubin, M Yuen, G Mueller, B Sloas, M Wood, L Balis, F Shearer, GM Brouwers, P Goldsmith, J Pizzo, PA Anderson, B Hirschfeld, S Sei, S Zeichner, S Roilides, E Clerici, M Wells, M Stocker, V Higham, C Townley, E Walsek, C Zwerski, S Heilman, N SelkinGutman, G Wolters, P Moss, H Jarosinski, P AF Lewis, LL Venzon, D Church, J Farley, M Wheeler, S Keller, A Rubin, M Yuen, G Mueller, B Sloas, M Wood, L Balis, F Shearer, GM Brouwers, P Goldsmith, J Pizzo, PA Anderson, B Hirschfeld, S Sei, S Zeichner, S Roilides, E Clerici, M Wells, M Stocker, V Higham, C Townley, E Walsek, C Zwerski, S Heilman, N SelkinGutman, G Wolters, P Moss, H Jarosinski, P TI Lamivudine in children with human immunodeficiency virus infection: A phase I/II study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HELPER CELL-FUNCTION; ZIDOVUDINE THERAPY; 2'-DEOXY-3'-THIACYTIDINE BCH-189; REVERSE-TRANSCRIPTASE; REPLICATION INVITRO; ORAL ZIDOVUDINE; HIV-INFECTION; TYPE-1; (-)-2'-DEOXY-3'-THIACYTIDINE; PHARMACOKINETICS AB The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day, Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decreased slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens. C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. RP Lewis, LL (reprint author), NCI,PEDIAT BRANCH,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 31 TC 67 Z9 68 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 JUL PY 1996 VL 174 IS 1 BP 16 EP 25 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UT468 UT WOS:A1996UT46800003 PM 8655986 ER PT J AU Busch, MP Operskalski, EA Mosley, JW Lee, TH Henrard, D Herman, S Sachs, DH Harris, M Huang, W Stram, DO AF Busch, MP Operskalski, EA Mosley, JW Lee, TH Henrard, D Herman, S Sachs, DH Harris, M Huang, W Stram, DO TI Factors influencing human immunodeficiency virus type 1 transmission by blood transfusion SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; SERONEGATIVE HOMOSEXUAL MEN; HIV-1 INFECTION; SEXUAL PARTNERS; QUALITY-CONTROL; HEMOPHILIACS; INDIVIDUALS; ANTIBODIES; RISK; SAFETY AB One hundred thirty-two recipients of blood components that retrospectively tested positive for antibody to human immunodeficiency virus type 1 (anti-HTV-1) were identified. Fourteen (11%) remained seronegative throughout follow-up. Donor and recipient characteristics that could have influenced transmission were examined. Attributes did not differ for infected and uninfected recipients. Peripheral blood mononuclear cells (PBMC) from uninfected recipients were HIV-1-negative by DNA amplification and culture but were susceptible to in vitro infection. Transmitting and nontransmitting donors at donation differed only for HIV-1 RNA positivity, By immunocapture reverse transcriptase-polymerase chain reaction, 6 of 11 transmitters and 0 of 11 nontransmitters tested RNA-positive (P = .02). A more sensitive quantitative RNA assay detected RNA in all donation sera, but median levels were higher in transmitting than nontransmitting sera (P = .01). Median CD4 cell counts were lower for transmitting than nontransmitting donors at enrollment (P .02). Level of viremia is an important determinant of HIV infection by blood transfusion. C1 UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90032. UNIV CALIF SAN FRANCISCO,IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. ABBOTT LABS,ABBOTT PK,IL 60064. ROCHE MOL SYST,BRANCHBURG,NJ. NCI,NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HB-4-7002, HB-9-7074, HB-4-7003] NR 53 TC 69 Z9 71 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 JUL PY 1996 VL 174 IS 1 BP 26 EP 33 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UT468 UT WOS:A1996UT46800004 PM 8656010 ER PT J AU Chougnet, C Wynn, TA Clerici, M Landay, AL Kessler, HA Rusnak, J Melcher, GP Sher, A Shearer, GM AF Chougnet, C Wynn, TA Clerici, M Landay, AL Kessler, HA Rusnak, J Melcher, GP Sher, A Shearer, GM TI Molecular analysis of decreased interleukin-12 production in persons infected with human immunodeficiency virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INTERFERON-GAMMA; CELLS; HIV AB Human immunodeficiency virus (HIV) disease is associated with loss of type 1 responses, including interleukin (IL)-12 production. The dramatic drop in p70 production seen at early stages of disease was found not to be associated with a similarly decreased p40 mRNA expression. p35 mRNA expression was more extensively reduced than p40 mRNA expression at these early stages, Monocytes infected in vitro with HIV displayed decreased p35 expression and p70 production, suggesting that such decreased IL-12 expression may contribute to reduced IL-12 production in HIV-positive patients' cells. In addition, treatment of cells with IL-10 increased IL-10 mRNA expression and decreased p40 expression in both MV-positive and -negative cells, while neutralization of IL-10 increased p40 mRNA levels. These observations, together with the observed hyperproduction of IL-10 in HIV-positive patients, may explain the dysregulation of IL-12 production seen in HIV disease. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. RUSH MED COLL,CHICAGO,IL 60612. WILFORD HALL USAF MED CTR,LACKLAND AFB,SAN ANTONIO,TX 78236. RP Chougnet, C (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B-17,10 CTR DR NSC 1360,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 35 TC 115 Z9 116 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 JUL PY 1996 VL 174 IS 1 BP 46 EP 53 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UT468 UT WOS:A1996UT46800006 PM 8656012 ER PT J AU Walker, RE Spooner, KM Kelly, G McCloskey, V Woody, JN Falloon, J Baseler, M Piscitelli, SC Davey, RT Polis, MA Kovacs, JA Masur, H Lane, HC AF Walker, RE Spooner, KM Kelly, G McCloskey, V Woody, JN Falloon, J Baseler, M Piscitelli, SC Davey, RT Polis, MA Kovacs, JA Masur, H Lane, HC TI Inhibition of immunoreactive tumor necrosis factor-alpha by a chimeric antibody in patients infected with human immunodeficiency virus type 1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MARROW TRANSPLANT PATIENTS; INTRAVENOUS IMMUNOGLOBULIN; ALVEOLAR MACROPHAGES; REPLICATION; EXPRESSION; HIV; PHARMACOKINETICS; CELLS AB Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to stimulate human immunodeficiency virus type 1 (HIV-1) replication, has been implicated in the pathogenesis of HIV-1 infection. Inhibition of TNF-alpha by a chimeric humanized monoclonal antibody, cA2, was investigated in 6 HIV-1-infected patients with CD4 cell counts <200/mm(3). Two consecutive infusions of 10 mg/kg 14 days apart were well tolerated, and a prolonged serum half-life for cA2 (mean, 257 +/- 70 h) was demonstrated. Serum immunoreactive TNF-alpha concentrations fell from a mean prestudy value of 6.4 pg/mL (range, 4.2-7.9) to 1.1 pg/mL (range, 0.5-2.2) 24 h after the first infusion and returned to baseline within 7-14 days. A similar response was seen after the second infusion. No consistent changes in CD4 cell counts or plasma HIV RNA levels were observed over 42 days. Future studies evaluating the therapeutic utility of long-term TNF-alpha suppression using anti-TNF-alpha antibodies are feasible and warranted. C1 NIAID,CTR CLIN,DEPT CRIT CARE MED,NIH,BETHESDA,MD 20892. NIAID PHARM,NIH,BETHESDA,MD 20892. SCI APPLICAT INT CORP,FREDERICK,MD. CENTOCOR INC,MALVERN,PA 19355. OI Polis, Michael/0000-0002-9151-2268 NR 24 TC 50 Z9 50 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1996 VL 174 IS 1 BP 63 EP 68 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UT468 UT WOS:A1996UT46800008 PM 8656014 ER PT J AU Wideroff, L Schiller, J Kirnbauer, R Schiffman, MH Tarone, RE Manos, MM Lowy, D AF Wideroff, L Schiller, J Kirnbauer, R Schiffman, MH Tarone, RE Manos, MM Lowy, D TI Serology of human papillomavirus type 16 infections: Where angels fear to tread? Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. KAISER FDN RES INST,DIV RES,OAKLAND,CA. UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,VIENNA,AUSTRIA. RP Wideroff, L (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,CELLULAR ONCOL LAB,EPN 443,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Hernandez, Jessica/G-6527-2011 NR 6 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1996 VL 174 IS 1 BP 238 EP 239 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UT468 UT WOS:A1996UT46800039 ER PT J AU Bale, SJ Compton, JG Russell, LJ DiGiovanna, JJ AF Bale, SJ Compton, JG Russell, LJ DiGiovanna, JJ TI Genetic heterogeneity in lamellar ichthyosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter C1 NIAMSD,INTRAMURAL RES PROGRAM,DERMATOL CLIN RES UNIT,NIH,BETHESDA,MD 20892. RP Bale, SJ (reprint author), NIAMSD,INTRAMURAL RES PROGRAM,GENET STUDIES SECT,NIH,6 CTR DR,MSC-2757,BETHESDA,MD 20892, USA. NR 1 TC 4 Z9 4 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 JUL PY 1996 VL 107 IS 1 BP 140 EP 140 DI 10.1111/1523-1747.ep12298430 PG 1 WC Dermatology SC Dermatology GA UU897 UT WOS:A1996UU89700026 PM 8752853 ER PT J AU Combadiere, C Ahuja, SK Tiffany, HL Murphy, PM AF Combadiere, C Ahuja, SK Tiffany, HL Murphy, PM TI Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1 alpha, MIP-1 beta, and RANTES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemotaxis; inflammation; G protein ID HUMAN INTERLEUKIN-8 RECEPTOR; CHEMOATTRACTANT PROTEIN-1; CHEMOTACTIC CYTOKINES; MOLECULAR-CLONING; IDENTIFICATION; LYMPHOCYTES; MCP-2; CELLS AB We have cloned a human cDNA for a novel CC chemokine receptor (CC CKR) designated CC CKR5 that has 48-75% amino acid identity to other CC CKRs, CC CKR5 mRNA was detected constitutively in primary adherent monocytes but not in primary neutrophils or eosinophils, Macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES were all potent agonists for CC CKR5 (EC(50) = 3-30 nM) when calcium flux was measured in transfected HEK 293 cells, yet the apparent binding affinities of the corresponding iodinated chemokines to intact cells expressing the receptor were low (IC50 similar to 100 nM). The calcium flux responses were completely blocked by treatment of transfected cells with pertussis toxin, These data suggest that CC CKR5 is a G(i)-coupled receptor that may mediate monocyte responses to MIP-1 alpha, MIP-1 beta, and RANTES. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 36 TC 221 Z9 227 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 1996 VL 60 IS 1 BP 147 EP 152 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UX998 UT WOS:A1996UX99800019 PM 8699119 ER PT J AU Kuszewski, J Gronenborn, AM Clore, GM AF Kuszewski, J Gronenborn, AM Clore, GM TI A potential involving multiple proton chemical-shift restraints for nonstereospecifically assigned methyl and methylene protons SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID PROTEINS; NMR C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 10 TC 25 Z9 25 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 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUL PY 1996 VL 112 IS 1 BP 79 EP 81 DI 10.1006/jmrb.1996.0113 PG 3 WC Physics, Atomic, Molecular & Chemical SC Physics GA UW492 UT WOS:A1996UW49200012 PM 8661311 ER PT J AU deZwart, JA vanGelderen, P Kelly, DJ Moonen, CTW AF deZwart, JA vanGelderen, P Kelly, DJ Moonen, CTW TI Fast magnetic-resonance temperature imaging SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID GRADIENT-RECALLED MRI; MOLECULAR-DIFFUSION; TIME C1 NIH,VIVO NMR RES CTR,BETHESDA,MD 20892. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 18 TC 53 Z9 52 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUL PY 1996 VL 112 IS 1 BP 86 EP 90 DI 10.1006/jmrb.1996.0115 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA UW492 UT WOS:A1996UW49200014 PM 8661313 ER PT J AU Biesecker, LG Graham, JM AF Biesecker, LG Graham, JM TI Pallister-Hall syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE hypothalamic hamartoma; polydactyly; imperforate anus; hypopituitarism ID CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; AUTOSOMAL-DOMINANT TRANSMISSION; SYNDROME TYPE-VI; IMPERFORATE ANUS; HYPOPITUITARISM; DELINEATION; HAMARTOMA; SIBS C1 UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,SCH MED,DIV CLIN GENET & DYSMORPHOL,LOS ANGELES,CA 90048. RP Biesecker, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 49,ROOM 4A80,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [2P01 HD22657-06] NR 33 TC 41 Z9 41 U1 1 U2 1 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 JUL PY 1996 VL 33 IS 7 BP 585 EP 589 DI 10.1136/jmg.33.7.585 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA UX094 UT WOS:A1996UX09400011 PM 8818945 ER PT J AU Clark, CH Hedaya, RJ Rosenthal, NE AF Clark, CH Hedaya, RJ Rosenthal, NE TI Seasonal depression in patients with dissociative disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID MULTIPLE PERSONALITY-DISORDER; MANIA C1 GEORGETOWN UNIV HOSP,DEPT PSYCHIAT,WASHINGTON,DC. RP Clark, CH (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. NR 20 TC 0 Z9 0 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1996 VL 184 IS 7 BP 433 EP 437 DI 10.1097/00005053-199607000-00007 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UY953 UT WOS:A1996UY95300007 PM 8691197 ER PT J AU Newman, JD AF Newman, JD TI The information continuum: Evolution of social information transfer in monkeys, apes, and hominids - King,BJ SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Newman, JD (reprint author), NICHHD,NIH,POOLESVILLE,MD 20837, USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1996 VL 184 IS 7 BP 448 EP 449 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UY953 UT WOS:A1996UY95300015 ER PT J AU Giorgi, O Orlandi, M Lecca, D Serra, GP Zhang, L Corda, MG AF Giorgi, O Orlandi, M Lecca, D Serra, GP Zhang, L Corda, MG TI Kinetics of tert-[S-35]butylbicyclophosphorothionate binding in the cerebral cortex of newborn and adult rats: Effects of GABA and receptor desensitization SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE GABA(A) receptor; tert-[S-35]butylbicyclophosphorothionate binding; kinetics; receptor desensitization; ontogenesis; cerebral cortex of the rat ID GAMMA-AMINOBUTYRIC-ACID; SUBUNIT MESSENGER-RNAS; A RECEPTOR; POSTNATAL-DEVELOPMENT; CHLORIDE IONOPHORE; XENOPUS OOCYTES; TBPS BINDING; BRAIN; CHANNEL; TERT-BUTYLBICYCLOPHOSPHOROTHIONATE AB The effects of GABA on the kinetics of tert[S-35]butylbicyclophosphorothionate ([S-35]TBPS) binding to the convulsant site of GABA(A) receptors were studied in membrane suspensions from the cerebral cortex of newborn (1-day-old) and adult (go-day-old) rats. TBPS dissociation was biphasic in neonates and adults, indicating that more than one interconvertible state of [S-35]TBPS binding sites may be present in the cerebral cortex. In the absence of GABA, the fast (t(1/2), 11 min) and slow (t(1/2), 77 min) components of TBPS dissociation in newborn rats were approximately fourfold slower than in adults, The acceleration of the dissociation rates caused by 2 mu M GABA, however, was more robust in neonates than in adults (six- to ninefold vs. twofold increase, respectively). Moreover, the dissociation rates of TBPS in membranes preincubated with 2 mu M GABA (dissociation started by adding 40 mu M picrotoxin) were two- to fourfold slower than in membranes preincubated without GABA (dissociation started by adding 40 mu M picrotoxin plus 2 mu M GABA). Taken together, these results suggest that (1) the closed state of GABA(A) receptors is associated with a more effective steric barrier for the binding of TBPS in neonates compared with adults, (2) GABA produces a larger acceleration of the binding kinetics of TBPS in neonates than in adults, and (3) long incubations with GABA may cause receptor desensitization, which in turn slows down the dissociation rates of TBPS. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Giorgi, O (reprint author), UNIV CAGLIARI,DEPT TOXICOL,VIALE A DIAZ 182,I-09126 CAGLIARI,ITALY. NR 29 TC 3 Z9 3 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 JUL PY 1996 VL 67 IS 1 BP 423 EP 429 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UQ687 UT WOS:A1996UQ68700052 PM 8667022 ER PT J AU Fukuhara, K Kvetnansky, R Cizza, G Pacak, K Ohara, H Goldstein, DS Kopin, IJ AF Fukuhara, K Kvetnansky, R Cizza, G Pacak, K Ohara, H Goldstein, DS Kopin, IJ TI Interrelations between sympathoadrenal system and hypothalamo-pituitary-adrenocortical/thyroid systems in rats exposed to cold stress SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE cold stress; catecholamines; catecholamine metabolites; adrenalectomy; thyroidectomy ID PHYSIOLOGICAL SIGNIFICANCE; IMMOBILIZATION STRESS; ADRENAL SYSTEM; TSH SECRETION; PLASMA-LEVELS; CATECHOLAMINES; HORMONE; THYROTROPIN; INHIBITION; 3,4-DIHYDROXYPHENYLALANINE AB The interrelations between sympathoadrenal (SA) system and hypothalamo-pituitary-adrenocortical (HPA) or hypothalamo-pituitary-thyroid (HPT) system during cold stress were examined by measuring plasma levels of dihydroxyphenylalanine (DOPA), catecholamine and their metabolites in adrenalectomized (ADX) and thyroidectomized CTX) rats exposed to cold stress (-3 degrees C). Plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), thyroid-stimulating hormone (TSH) and thyroid hormones in cold-stressed rats were measured also. Plasma ACTH levels were increased transiently after 1 h of cold exposure, after which the circadian rhythm and plasma levels of ACTH were similar to those of normal rats. Plasma CORT levels were also elevated after 1 h of cold exposure; the increased levels of CORT tended to return to normal levels after 9 h of cold, but remained higher than those of normal rats during at least 24 h of cold exposure. Plasma ACTH levels of 5 day cold-stressed rats were no longer elevated above those of control rats and plasma CORT levels were only slightly higher than in control animals. However, plasma levels of TSH and free thyroid hormones were elevated after 1 day and remained elevated after 5 days of cold exposure. Thus, cold stress appears to activate chronically the HPT system, but only transiently activates the HPA system. ADX rats had higher basal plasma levels of dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), DOPA and homovanillic acid (HVA) than those of sham-operated (SHAM) rats, but norepinephrine (NE) levels were not significantly greater than in SHAM animals. TX rats had higher basal plasma levels of NE, epinephrine (EPI) and dopamine (DA), as well as much higher plasma levels of the metabolites. Exposure to cold increased plasma NE levels in both ADX and TX rats, but the increments in TX rats were much greater than in SHAM and ADX groups. Plasma EPI levels were not significantly elevated during cold exposure in SHAM rats, but were highly elevated in TX rats exposed to cold. TX rats had much larger increments in plasma levels of DHPG, MHPG, DA, dihydroxyphenylacetic acid (DOPAC) and HVA during cold exposure than those of SHAM and ADX rats. These results are consistent with the view that endogenous glucocorticoids restrain responses of catecholamine synthesis, release, reuptake, and metabolism in sympathetic nervous system of cold-stressed animals, but that in the absence of an effective HPT system, there is enhanced sympathoadrenal medullary function and augmentation of their responses to cold as a means for maintaining body temperature when the HPT thermogenesis system is impaired. C1 SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,BRATISLAVA 83306,SLOVAKIA. NIMH,CLIN ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Fukuhara, K (reprint author), NIPPON ZOKI PHARMACEUT CO LTD,DEPT PHARMACOL 1,INST BIOACT SCI,YASHIRO CHO,KATO,HYOGO 67314,JAPAN. NR 50 TC 46 Z9 56 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUL PY 1996 VL 8 IS 7 BP 533 EP 541 DI 10.1046/j.1365-2826.1996.04877.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UX932 UT WOS:A1996UX93200008 PM 8843022 ER PT J AU Pacak, K Palkovits, M Makino, S Kopin, IJ Goldstein, DS AF Pacak, K Palkovits, M Makino, S Kopin, IJ Goldstein, DS TI Brainstem hemisection decreases corticotropin-releasing hormone mRNA in the paraventricular nucleus but not in the central amygdaloid nucleus SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE immobilization; ACTH; corticosterone ID INDUCED NOREPINEPHRINE RELEASE; REPEATED IMMOBILIZATION STRESS; MESSENGER-RNA; MEDIAN-EMINENCE; RAT-BRAIN; CONTAINING NEURONS; CONSCIOUS RATS; SPINAL-CORD; HYPOTHALAMUS; PROJECTIONS AB Corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus and in the central nucleus of the amygdala (ACE) participate in neurohumoral and behavioral responses to stress. To understand better the central regulation of CRH, the present study assessed the effects of ipsilateral surgical hemisection of the brainstem on expression of CRH mRNA in the PVN and the ACE. In situ hybridization was used to demonstrate PVN CRH mRNA expression in hemisected, sham-operated or intact rats before and after 3 h of immobilization (IMMO). In addition, hypothalamic-pituitary-adrenocortical (HPA) axis activity at baseline and during IMMO was assessed by measurements of plasma concentrations of ACTH and corticosterone. IMMO markedly increased CRH mRNA expression in the PVN in all experimental groups. Rats with brainstem hemisections had lower PVN CRH mRNA expression ipsilateral to the lesion and markedly blunted responses after IMMO, compared to values in sham-operated rats. In contrast, neither hemisection nor IMMO affected CRH mRNA expression in the ACE. Lesioned and SHAM-operated groups did not differ in baseline or IMMO-induced increases in plasma ACTH or corticosterone levels. The present results indicate that baseline levels and IMMO-induced increments in CRH mRNA expression in the PVN, but not in the ACE, depend on ipsilaterally ascending medullary tracts and that IMMO-induced HPA activation does not depend on these pathways. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 47 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUL PY 1996 VL 8 IS 7 BP 543 EP 551 DI 10.1046/j.1365-2826.1996.04888.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UX932 UT WOS:A1996UX93200009 PM 8843023 ER PT J AU Karp, BI Porter, S Toro, C Hallett, M AF Karp, BI Porter, S Toro, C Hallett, M TI Simple motor tics may be preceded by a premotor potential SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE tics; Tourette's syndrome; premotor potentials ID TOURETTES-SYNDROME; MOVEMENT AB Obese st al reported that simple motor ties in Tourette's syndrome were not associated with premotor potentials, which were present when patients mimicked their ties voluntarily, suggesting that spontaneous ties were not generated in the same manner as voluntary movements. Five patients with simple motor ties were studied using a similar paradigm. Premotor potentials were examined during spontaneous ties and during voluntary imitation of the tics. All patients had premotor negativity with the voluntary movements. As in the study of Obese et al, spontaneous ties were not preceded by premotor potentials in three patients. However, premotor negativity was present with spontaneous ties in two patients and resembled the NS' segment of the premotor potential seen with self paced, voluntary movements. A similar premotor potential pattern has been reported with voluntary movements performed in response to external triggering stimuli. In patients with Tourette's syndrome, the eliciting signals could be internal sensations. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RP Karp, BI (reprint author), NINCDS,OFF CLIN DIRECTOR,NIH,BLDG 10,ROOM 5N-226,BETHESDA,MD 20892, USA. NR 10 TC 55 Z9 55 U1 0 U2 2 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 JUL PY 1996 VL 61 IS 1 BP 103 EP 106 DI 10.1136/jnnp.61.1.103 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA UW072 UT WOS:A1996UW07200024 PM 8676135 ER PT J AU Salvatore, M Pocchiari, M Cardone, F Petraroli, R DAlessandro, M Galvez, S Brown, P Macchi, G Fieschi, C Colosimo, C AF Salvatore, M Pocchiari, M Cardone, F Petraroli, R DAlessandro, M Galvez, S Brown, P Macchi, G Fieschi, C Colosimo, C TI Codon 200 mutation in a new family of Chilean origin with Creutzfeldt-Jakob disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Letter ID PRION PROTEIN GENE C1 IST SUPER SANITA,VIROL LAB,SECT PERSISTENT & SLOW VIRUS INFECT,I-00161 ROME,ITALY. INST NEUROCIRUG & INVEST CEREBRALES,SANTIAGO,CHILE. NINCDS,CNS STUDIES LAB,NIH,BETHESDA,MD 20892. UNIV CATTOLICA,IST NEUROL,ROME,ITALY. UNIV ROMA LA SAPIENZA,DIPARTIMENTO SCI NEUROL,NEUROL CLIN 1,ROME,ITALY. RI Cardone, Franco/D-1724-2009; salvatore, mirella/K-6691-2016 OI Cardone, Franco/0000-0002-2376-0470; salvatore, mirella/0000-0002-8296-0376 NR 6 TC 8 Z9 8 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 1996 VL 61 IS 1 BP 111 EP 112 DI 10.1136/jnnp.61.1.111 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA UW072 UT WOS:A1996UW07200026 PM 8676137 ER PT J AU Murphy, DD Segal, M AF Murphy, DD Segal, M TI Regulation of dendritic spine density in cultured rat hippocampal neurons by steroid hormones SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dendritic spines; estradiol; culture; hippocampal neurons; calcium; plasticity ID LONG-TERM POTENTIATION; CALCIUM; STIMULATION; SYNAPSES; SLICE; CELLS AB The effects of gonadal steroid hormones on dendritic spines were studied in hippocampal neurons that were dissociated and grown in culture for 2-3 weeks, Exposure to estradiol caused up to a twofold increase in dendritic spine density in these neurons. The effect of estradiol was stereospecific and blocked by the steroid antagonist tamoxifen. The estradiol-induced rise in spine density was blocked by the NMDA antagonist APV, but not by the AMPA/KA antagonist DNQX. The estradiol-induced rise in spine density was blocked by the serine/threonine kinase inhibitor H7, but not by the tyrosine kinase inhibitor genestein, and was partially mimicked by PMA, an activator of protein kinase C. Estradiol also caused an increase in the fluorescence intensity of synaptophysin-immunoreactive terminals, corresponding to presynaptic boutons. Finally, estradiol caused a rise in [Ca](i) reactivity of the cultured neurons to topical application of glutamate, These studies are the first to examine receptor and second messenger regulation of dendritic spines, and they illustrate the viability of cultured neurons as a powerful test system to address issues related to the regulation of dendritic spine maturation. C1 WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 27 TC 303 Z9 314 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 1996 VL 16 IS 13 BP 4059 EP 4068 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UT323 UT WOS:A1996UT32300002 PM 8753868 ER PT J AU Svingos, AL Moriwaki, A Wang, JB Uhl, GR Pickel, VM AF Svingos, AL Moriwaki, A Wang, JB Uhl, GR Pickel, VM TI Ultrastructural immunocytochemical localization of mu-opioid receptors in rat nucleus accumbens: Extrasynaptic plasmalemmal distribution and association with Leu(5)-enkephalin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mu-opioid receptor; reinforcement; striatum; enkephalin; morphine; opiates ID DELTA-OPIATE RECEPTORS; ADENYLATE-CYCLASE; AUTORADIOGRAPHIC LOCALIZATION; ACETYLCHOLINE-RELEASE; MEDIATED INHIBITION; PRIMARY CULTURES; BRAIN; ENKEPHALIN; NEURONS; NEOSTRIATUM AB mu-Opioid receptors and their endogenous ligands, including Leu(5)-enkephalin (LE), are distributed abundantly in the nucleus accumbens (NAC), a region implicated in mechanisms of opiate reinforcement. We used immunoperoxidase and/or immunogold-silver methods to define ultrastructural sites for functions ascribed to mu-opioid receptors and potential sites for activation by LE in the NAC. An antipeptide antibody raised against an 18 aminoacid sequence of the cloned mu-opioid receptor (MOR) C terminus showed that MOR-like immunoreactivity (MOR-LI) was localized predominantly to extrasynaptic sites along neuronal plasma membranes, The majority of neuronal profiles containing MOR-LI were dendrites and dendritic spines, The dendritic plasma membranes immunolabeled for MOR were near sites of synaptic input from LE-labeled terminals and other unlabeled terminals forming either inhibitory or excitatory type synapses, Unmyelinated axons and axon terminals were also intensely but less frequently immunoreactive for MOR. Observed sites for potential axonal associations with LE included coexistence of MOR and LE within the same terminal, as well as close appositions between differentially labeled axons, Astrocytic processes rarely contained detectable MOR-LI, but also were sometimes observed in apposition to LE-labeled terminals. We conclude that in the rat NAC, MOR is localized prominently to extrasynaptic neuronal and more rarely to glial plasma membranes that are readily accessible to released LE and possibly other opioid peptides and opiate drugs, The close affiliation of MOR with spines receiving excitatory synapses and dendrites receiving inhibitory synapses provides the first direct morphological evidence that MOR selectively modulates postsynaptic responses to cortical and other afferents. C1 NIDA,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT NEUROSCI,BALTIMORE,MD 21224. RP Svingos, AL (reprint author), CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,DIV NEUROBIOL,411 E 69TH ST,NEW YORK,NY 10021, USA. FU NIDA NIH HHS [DA04600] NR 70 TC 79 Z9 80 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 1996 VL 16 IS 13 BP 4162 EP 4173 PG 12 WC Neurosciences SC Neurosciences & Neurology GA UT323 UT WOS:A1996UT32300012 PM 8753878 ER PT J AU Takeshima, T Shimoda, K Johnston, JM Commissiong, JW AF Takeshima, T Shimoda, K Johnston, JM Commissiong, JW TI Standardized methods to bioassay neurotrophic factors for dopaminergic neurons SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE dopaminergic neurotrophic factor (DNTF); microisland culture; imaging; tissue culture; mesencephalic dopaminergic neuron (MDN); Parkinson's disease; growth factor; target-derived neurotrophic factor (TD-NTF) ID FIBROBLAST GROWTH-FACTOR; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; PROMOTES SURVIVAL; ADULT-RAT; MESENCEPHALIC GLIA; SERUM DEPRIVATION; CELL-CULTURE; SPINAL-CORD; IN-VIVO AB The search for specific neurotrophic factors that will eventually be used to reduce or arrest the rare of degeneration of dopaminergic neurons in Parkinson's disease is being pursued by first testing the ability of putative compounds to increase the survival of dopaminergic neurons in primary cultures of the fetal, ventral mesencephalon. This research has intensified in recent years, The experimental procedures used by different laboratories in these studies differ widely, and meaningful comparisons of the results obtained are accordingly difficult to make. Some important experimental variables include the age of the fetal tissue used; the dissection technique used to isolate the ventral mesencephalon; the percentage of dopaminergic neurons present in the culture initially; handling of the tissue during dissection; the technique used to disperse the cells; the use of serum; the technique of plating the cells; the attachment factors used; detachment and loss of cells during the staining procedure; the age of the cultures at the time of analysis; the uneven distribution of cells at the time of analysis and the use of imaging techniques in the analysis, We show that when the E14 rat embryo is used, it is possible to consistently obtain a culture with 20% of tyrosine hydroxylase-positive neurons. Neither the plating density in the range of 7.8 x 10(3) to 1.25 x 10(5) cells/cm(2), nor the percentage of serum in the growth medium affected the percentage of cells that expressed TH initially, at 4 or 12 h after plating, When the cells were plated as 25 mu l droplets, called microislands (area approximate to 12.5 mm(2)), and allowed to attach before additional growth medium was added, cell density remained uniform at the center of the microisland for the duration of the culture, Restriction of the analysis of cell survival to the Center of the microisland therefore helped to decrease the variability in counting that could occur when cells are dispersed over a larger area. In contrast, in an 8-well chamber slide or 35 mm petri dish, in which the whole area is plated, cell density was consistently higher at the edge (edge effect), versus the centre, by a factor of about three, The use of microisland cultures also has the additional benefit of increasing by a factor of about five the number of individual cultures that can be set up per litter, and a proportionate reduction in the number of animals used per experiment, When the percentage of serum in the growth medium was 0% always, or 10% for the first 12 h, and 0% thereafter, or 10% always, the number of TH-pos neurons per field (using a x 20 objective, column factor 1.25; area 320 mu m(2)) after 5 days in culture (DIV5) was < 1, 3-8 and 14-22, respectively. Under the same experimental conditions, the number of neurons (MAP2-positive) per field was 5-8, 18-30 and 45-65 (N = 10 in all cases), respectively, Serum deprivation therefore has a highly deleterious effect on neuronal survival in culture, We suggest that cultures that were exposed to serum at any stage of the experiment, should not be referred to as 'serum-free', since even a brief exposure to serum exerts a protective effect on neurons, and especially on dopaminergic neurons. Instead, the percentage and kind of serum used, the exact usage, and the duration of exposure of the cells to serum should be stated. Finally, it is suggested that where possible, an imaging system with manual count and journaling capabilities be used in the analysis. The methods described are illustrated by dose-response curves of the neurotrophic effects of BDNF, NGF-beta and IL-6 versus percentage survival on dopaminergic neurons, when grown in serum-free medium throughout. C1 NINCDS,LMB,NIH,BETHESDA,MD 20892. NINCDS,NEURAL TRANSPLANTAT UNIT,LMCN,NIH,BETHESDA,MD 20892. NATL NISHI TOTTORI HOSP,DIV NEUROL,TOTTORI 68902,JAPAN. NR 50 TC 45 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUL PY 1996 VL 67 IS 1 BP 27 EP 41 DI 10.1016/S0165-0270(96)00002-7 PG 15 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VA764 UT WOS:A1996VA76400004 PM 8844522 ER PT J AU Schmidt, ME Ernst, M Matochik, JA Maisog, JM Pan, BS Zametkin, AJ Potter, WZ AF Schmidt, ME Ernst, M Matochik, JA Maisog, JM Pan, BS Zametkin, AJ Potter, WZ TI Cerebral glucose metabolism during pharmacologic studies: Test-retest under placebo conditions SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE validation; placebo; FDG-PET ID POSITRON EMISSION TOMOGRAPHY; F-18 2-FLUORO-2-DEOXY-D-GLUCOSE METHOD; BLOOD-FLOW; PET; REPRODUCIBILITY; VARIABILITY; HABITUATION; VALIDATION; ANXIETY; HUMANS AB The reliability of serial [F-18]fluorodeoxyglucose (FDG) PET scans for psychopharmacologic studies was tested by using placebo infusions. Methods: FDG scans were obtained before and after a 30 min placebo infusion (n = 10; Group 1) or after each of two bolus infusions with placebo (n = 8; Group 2). Subjects performed a continuous performance task (CPT) during each scan. Cardiovascular measures and ratings of anxiety were obtained in all subjects. Samples for determination of plasma norepinephrine (NE) were taken at multiple time points in Group 1. Results: A slight increase in apparent global metabolism occurred between scans in both Groups 1 and 2. A few regions significantly increased in both groups. While an apparent increase in sympathetic activity occurred during the placebo infusion, neither NE levels, anxiety ratings nor cardiovascular measures correlated with global or regional FDG uptake. Conclusion: Test-retest differences of global and regional glucose metabolism were highly consistent across two experimental designs. While increases in cerebral glucose metabolism appeared to occur during the second scan, differences between scans were small. This method may offer advantages for selected psychopharmacologic studies. C1 NIMH,SECT CLIN BRAIN IMAGING,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,SECT FUNCT BRAIN IMAGING,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. RP Schmidt, ME (reprint author), NIMH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,ROOM 2D46,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 37 TC 20 Z9 20 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1996 VL 37 IS 7 BP 1142 EP 1149 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UV693 UT WOS:A1996UV69300023 PM 8965185 ER PT J AU Villemagne, VL Phillips, RL Liu, X Gilson, SF Dannals, RF Wong, DF Harris, PJ Ruff, M Pert, C Bridge, P London, ED AF Villemagne, VL Phillips, RL Liu, X Gilson, SF Dannals, RF Wong, DF Harris, PJ Ruff, M Pert, C Bridge, P London, ED TI Peptide T and glucose metabolism in AIDS dementia complex SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE AIDS dementia; peptide T; glucose metabolism; brain imaging ID RECEPTOR-BINDING; ENVELOPE; DISEASE; BRAIN; HIV; INFECTIVITY AB AIDS dementia complex (ADC) is the most common presenting neurologic manifestation of human immunodeficiency virus (HIV)-1 infection. We report FDG-PET studies in a 39 yr-old man who had ADC and completed a 12-wk treatment protocol with 1.2 mg/day of intranasal peptide T, one before and one after 12 wk of treatment with peptide T. Peptide T is an octapeptide under investigation for treatment of ADC patients. Values of rCMRglc were converted to Z scores using the mean and standard deviation of values of rCMRglc in three HIV-seronegative matched controls, each of which was studied twice, at the beginning and end of a 12-wk interval. Thirty-five of 60 regions assayed showed Z scores with absolute values greater than or equal to 3 (considered abnormal) in the baseline study. Regions with high absolute values of Z scores were located in subcortical areas and in the limbic system, and to a lesser degree in the frontal, temporal and parietal robes. Thirty-four of these 35 regions showed remission (decrease in the absolute values of Z scores) after treatment. Only one region showed no improvement in the second study. Three regions with absolute values of Z scores <3 in the baseline study manifested Z scores with magnitudes greater than or equal to 3 in the second study. These preliminary observations suggest that functional neuroimaging techniques provide a useful tool in the evaluation of the response to treatment in ADC patients. C1 NIDA,BRAIN IMAGING SECT,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. AIDS CLIN RES CTR,WASHINGTON,DC. PEPTIDE RES,ROCKVILLE,MD. NIDA,NIH,MED DEV DIV,ROCKVILLE,MD. AIDS CLIN RES CTR,BALTIMORE,MD. FU NINDS NIH HHS [NS-15080] NR 26 TC 18 Z9 18 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1996 VL 37 IS 7 BP 1177 EP 1180 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UV693 UT WOS:A1996UV69300031 PM 8965193 ER PT J AU Stoll, BJ Gordon, T Korones, SB Shankaran, S Tyson, JE Bauer, CR Fanaroff, AA Lemons, JA Donovan, EF Oh, W Stevenson, DK Ehrenkranz, RA Papile, LA Verter, J Wright, LL AF Stoll, BJ Gordon, T Korones, SB Shankaran, S Tyson, JE Bauer, CR Fanaroff, AA Lemons, JA Donovan, EF Oh, W Stevenson, DK Ehrenkranz, RA Papile, LA Verter, J Wright, LL TI Late-onset sepsis in very low birth weight neonates: A report from the National Institute of Child Health and Human Development Neonatal Research Network SO JOURNAL OF PEDIATRICS LA English DT Article ID SEPTICEMIA AB Objective: Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 7861 VLBW (401 to 1500 gm) neonates admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991 to 1993). Methods: The NICHD Neonatal Research Network maintains a prospectively collected registry of all VLBW neonates cared for at participating centers. Data from this registry were analyzed retrospectively. Results: Of 6911 infants who survived beyond 3 days, 1696 (25%) had one or more episodes of blood culture-proven sepsis. The vast majority of infections (73%) were caused by gram-positive organisms, with coagulase-negative staphylococci accounting for 55% of all infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of infection included intubation, respiratory distress syndrome, prolonged ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, severe intraventricular hemorrhage, and necrotizing enterocolitis. Among infants with bronchopulmonary dysplasia, those with late-onset sepsis had a significantly longer duration of mechanical ventilation (45 vs 33 days; p < 0.01). Late-onset sepsis prolonged hospital stay: the mean number of days in the hospital for VLBW neonates with and without late-onset sepsis was 86 and 61 days, respectively (p < 0.001). Even after adjustment for other complications of prematurity, including intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia, infants with late-onset sepsis had a significantly longer hospitalization (p < 0.001). Moreover, neonates in whom late-onset sepsis developed were significantly more likely to die than those who were uninfected (17% vs 7%; p < 0.0001), especially if they were infected with gram-negative organisms (40%) or fungi (28%), Deaths attributed to infection increased with increasing chronologic age. Whereas only 4% of deaths in the first 3 days of life were attributed to infection, 45% of deaths after 2 weeks were related to infection. Conclusions: Late-onset sepsis is a frequent and important problem among VLBW preterm infants. Successful strategies to decrease late-onset sepsis should decrease VLBW mortality rates, shorten hospital stay, and reduce costs. C1 GEORGE WASHINGTON UNIV, CTR BIOSTAT, ROCKVILLE, MD USA. UNIV TENNESSEE, MEMPHIS, TN USA. UNIV TEXAS, SW MED CTR, DALLAS, TX 75235 USA. UNIV MIAMI, MIAMI, FL 33152 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. INDIANA UNIV, INDIANAPOLIS, IN 46204 USA. UNIV CINCINNATI, CINCINNATI, OH USA. WOMEN & INFANTS HOSP RHODE ISL, PROVIDENCE, RI USA. STANFORD UNIV, STANFORD, CA USA. YALE UNIV, NEW HAVEN, CT USA. UNIV NEW MEXICO, ALBUQUERQUE, NM 87131 USA. NICHHD, BETHESDA, MD 20892 USA. RP Stoll, BJ (reprint author), EMORY UNIV, SCH MED, DEPT PEDIAT, 2040 RIDGEWOOD DR, ATLANTA, GA 30322 USA. FU NICHD NIH HHS [HD21397, HD27853, HD27871] NR 16 TC 389 Z9 407 U1 0 U2 6 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 JUL PY 1996 VL 129 IS 1 BP 63 EP 71 DI 10.1016/S0022-3476(96)70191-9 PG 9 WC Pediatrics SC Pediatrics GA UY272 UT WOS:A1996UY27200010 PM 8757564 ER PT J AU Stoll, BJ Gordon, T Korones, SB Shankaran, S Tyson, JE Bauer, CR Fanaroff, AA Lemons, JA Donovan, EF Oh, W Stevenson, DK Ehrenkranz, RA Papile, LA Verter, J Wright, LL AF Stoll, BJ Gordon, T Korones, SB Shankaran, S Tyson, JE Bauer, CR Fanaroff, AA Lemons, JA Donovan, EF Oh, W Stevenson, DK Ehrenkranz, RA Papile, LA Verter, J Wright, LL TI Early-onset sepsis in very low birth weight neonates. A report from the National Institute of Child Health and Human Development Neonatal Research Network SO JOURNAL OF PEDIATRICS LA English DT Article ID SEPTICEMIA; INFECTION; EVOLUTION; INFANTS AB Objective: Early-onset sepsis (occurring within 72 hours of birth) is included in the differential diagnosis of most very low birth weight (VLBW) neonates. To determine the current incidence of early-onset sepsis, risk factors for disease, and the impact of early-onset sepsis on subsequent hospital course, we studied a cohort of 7861 VLBW neonates (401 to 1500 gm) admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991-1993). Methods The NICHD Neonatal Research Network maintains a prospectively collected registry on all VLBW neonates born or cared for at participating centers, Data from this registry were analyzed retrospectively. Results: Blood culture-proven early-onset sepsis was uncommon, occurring in only 1.9% of VLBW neonates, Group B streptococcus was the most frequent pathogen associated with early-onset sepsis (31%), followed by Escherichia coli (16%) and Haemophilus influenzae (12%). Decreasing gestational age was associated with increased rates of infection. Antibiotic therapy for suspected sepsis is frequently initiated at birth in VLBW neonates, Almost half of the infants in this cohort were considered to have clinical sepsis and continued to receive antibiotics for 5 or more days, despite a negative blood culture result in 98% of cases. These findings underscore the difficulty of ruling out sepsis in the symptomatic immature neonate and the special concern for culture-negative clinical sepsis in the face of maternal antibiotic use. Neonates with early-onset sepsis were significantly more likely to have subsequent comorbidities, including severe intraventricular hemorrhage, patent ductus arteriosus, and prolonged assisted ventilation. Although 26% of VLBW neonates with early-onset sepsis died, only 4% of the 950 deaths that occurred in the first 72 hours of life were attributed to infection. For those infants discharged alive, early-onset sepsis was associated with a significantly prolonged hospital stay (86 vs 69 days; p < 0.02). Conclusions: Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants. Improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected VLBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected. C1 GEORGE WASHINGTON UNIV, CTR BIOSTAT, ROCKVILLE, MD USA. UNIV TENNESSEE, MEMPHIS, TN USA. WAYNE STATE UNIV, DETROIT, MI USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. UNIV MIAMI, MIAMI, FL 33152 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. INDIANA UNIV, INDIANAPOLIS, IN 46204 USA. UNIV CINCINNATI, CINCINNATI, OH USA. WOMEN & INFANTS HOSP RHODE ISL, PROVIDENCE, RI USA. STANFORD UNIV, STANFORD, CA 94305 USA. YALE UNIV, NEW HAVEN, CT USA. UNIV NEW MEXICO, ALBUQUERQUE, NM 87131 USA. NICHHD, BETHESDA, MD 20892 USA. RP Stoll, BJ (reprint author), EMORY UNIV, SCH MED, DEPT PEDIAT, 2040 RIDGEWOOD DR, ATLANTA, GA 30322 USA. FU NICHD NIH HHS [HD27871, HD21397, HD27853] NR 23 TC 211 Z9 220 U1 0 U2 4 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 JUL PY 1996 VL 129 IS 1 BP 72 EP 80 DI 10.1016/S0022-3476(96)70192-0 PG 9 WC Pediatrics SC Pediatrics GA UY272 UT WOS:A1996UY27200011 PM 8757565 ER PT J AU Comeau, AM Pitt, J Hillyer, GV Landesman, S Bremer, J Chang, BH Lew, J Moye, J Grady, GF McIntosh, K AF Comeau, AM Pitt, J Hillyer, GV Landesman, S Bremer, J Chang, BH Lew, J Moye, J Grady, GF McIntosh, K TI Early detection of human immunodeficiency virus on dried blood spot specimens: Sensitivity across serial specimens SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYMERASE CHAIN-REACTION; INFECTION; TRANSMISSION; HIV; REPLICATION; DIAGNOSIS; CHILDREN; INFANTS; TYPE-1; BIRTH AB Objective: To evaluate the use of dried blood spot (DBS) specimens and the early diagnostic value of the polymerase chain reaction (PCR) for detection of the human immunodeficiency virus (HIV) in DBS specimens collected at predefined age intervals from a large cohort of U.S. infants at risk of congenital or perinatal HIV infection. Design: We assayed available DBS specimens (n = 272) obtained during the first 4 months of life from 144 infants (41 infected, 103 uninfected) born to HIV-infected mothers enrolled in the Women and Infants Transmission Study. The DBS PCR results were compared with infant HIV infection status, PCR on liquid blood, and viral culture results. Analyses also included sensitivity and specificity of assay as related to the age of the infant when the specimen was obtained. Results: The DBS specimen PCR results were concordant with results from liquid blood specimens and with results from viral culture. The DBS PCR was highly specific for all age groups. Sensitivity in detecting HIV infection status rapidly increased during the first month of life, from 19% (5/26) by 1 week to 96% (25/26) by 1 month of age. Specimens obtained on the day of birth or the next day were the least likely to have detectable HIV DNA. Conclusions: The PCR assay of DBS specimens is a reliable tool for the early diagnosis of HIV infection and has important advantage over that of liquid blood DNA PCR and viral culture. These advantages include a lower volume of blood required for testing, increased safety, and ease of storage or transport of specimens, Thus DBS PCR is a useful test for clinical and epidemiologic tracking of infants at risk of HIV infection. C1 COLUMBIA UNIV COLL PHYS & SURG, DEPT PEDIAT, DIV INFECT DIS, NEW YORK, NY USA. UNIV PUERTO RICO, MED CTR, SAN JUAN, PR 00936 USA. SUNY BUFFALO, BROOKLYN, NY USA. RUSH PRESBYTERIAN ST LUKES MED CTR, DEPT MICROBIOL IMMUNOL, CHICAGO, IL USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. NICHHD, NIAID, PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH, DIV AIDS, BETHESDA, MD USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. CHILDRENS HOSP, BOSTON, MA 02115 USA. BOSTON CITY HOSP, BOSTON, MA 02118 USA. UNIV MASSACHUSETTS, MED CTR, WORCESTER, MA USA. RP Comeau, AM (reprint author), THEOBALD SMITH RES INST INC, NEW ENGLAND REG NEWBORN SCREENING PROGRAM, 305 S ST, JAMAICA PLAIN, MA 02130 USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [N01-AI-82505]; NICHD NIH HHS [N01-HD-2917, N01-HD-8-2913] NR 15 TC 45 Z9 46 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 JUL PY 1996 VL 129 IS 1 BP 111 EP 118 DI 10.1016/S0022-3476(96)70197-X PG 8 WC Pediatrics SC Pediatrics GA UY272 UT WOS:A1996UY27200016 PM 8757570 ER PT J AU Yanovski, JA Yanovski, SZ Cutler, GB Chrousos, GP Filmer, KM AF Yanovski, JA Yanovski, SZ Cutler, GB Chrousos, GP Filmer, KM TI Differences in the hypothalamic-pituitary-adrenal axis of black girls and white girls SO JOURNAL OF PEDIATRICS LA English DT Article ID RACIAL-DIFFERENCES; BODY-COMPOSITION; WOMEN; OBESITY; PLASMA; BLOOD; CORTICOTROPIN; HYPERTENSION; ALDOSTERONE; CHILDREN AB After intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma corticotropin (ACTH) concentrations of adult black women and men are approximately twice as high as those of adult white women and men; however, there are no corresponding differences in cortisol response, To determine whether these differences in ACTH secretion are also present in prepubertal and early pubertal girls, we studied the hypothalamic-pituitary-adrenal axis of 19 black and 19 white girls of normal weight (age 7 to 10 years) who were matched for body mass index, age, and socioeconomic status. Measures of cortisol's effects, including waist circumference, waist/hip ratio, and fasting insulin and glucose levels, were obtained and related to the ACTH and cortisol responses to 1 mu g/kg CRH, There were no racial differences in waist circumference, waist/hip ratio, fasting glucose or insulin levels, baseline free or total plasma cortisol levels, baseline ACTH concentrations, or the plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in a polyclonal radioimmunoassay, were significantly greater in prepubertal and early pubertal black girls than in white girls at all time points between 15 and 90 minutes after administration of CRH (area under curve (AUG) 1754 +/- 121 pmol/L . min in black girls vs 1304 +/- 124 pmol/L . min in white girls, p < 0.001), This difference was confirmed by an immunoradiometric assay believed to be specific for intact ACTH (AUG 1634 +/- 139 pmol/L . min in black girls vs 1224 +/- 104 pmol/L . min in white girls, p < 0.001), Neither ACTH AUC nor cortisol AUC was significantly correlated with body mass index in either black or white girls. We conclude that there are differences in the hypothalamic-pituitary-adrenal axis of prepubertal and early pubertal black and white girls similar to those found previously in adult women, The cause of these differences remains to be elucidated. C1 NICHHD, WARREN GRANT MAGNUSON CLIN CTR, DEV ENDOCRINOL BRANCH, BETHESDA, MD USA. NIDDKD, DIV DIGEST DIS & NUTR, NIH, BETHESDA, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 44 TC 17 Z9 17 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1996 VL 129 IS 1 BP 130 EP 135 DI 10.1016/S0022-3476(96)70199-3 PG 6 WC Pediatrics SC Pediatrics GA UY272 UT WOS:A1996UY27200018 PM 8757572 ER PT J AU Llanes, F SanzOrtega, J Suarez, B SanzEsponera, J AF Llanes, F SanzOrtega, J Suarez, B SanzEsponera, J TI Hepatocellular carcinomas diagnosed following metastasis to the oral cavity. Report of 2 cases SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE neoplasm metastasis; mouth neoplasms; tonsillar neoplasms; carcinoma, hepatocellular AB ORAL METASTASES FROM hepatocellular carcinomas are rare. Case 1 was a 66-year-old male without previous history of liver disease who presented with metastasis to the gingival jaw mucosae on the lingual side. Case 2 was a 71-year-old male, with a previous history of diabetes, hepatitis, and cirrhosis who presented with metastasis to the right palatine tonsil. Oral metastases were the first manifestation of the hepatocellular carcinoma in both cases. A review of the literature disclosed 20 cases of hepatocellular carcinoma metastasizing to the oral cavity, 7 affecting the gingival mucosae and none of them affecting the palatine tonsil. C1 NCI,BETHESDA,MD 20892. RP Llanes, F (reprint author), HOSP UNIV SAN CARLOS,DEPT ANAT PATOL,MARTIN LAGOS SN,MADRID 28040,SPAIN. RI Sanz, Julian/G-5276-2013 NR 7 TC 33 Z9 34 U1 0 U2 3 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUL PY 1996 VL 67 IS 7 BP 717 EP 719 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UZ358 UT WOS:A1996UZ35800010 PM 8832483 ER PT J AU Ye, JM Lee, GE Potti, GK Galelli, JF Wolfe, JL AF Ye, JM Lee, GE Potti, GK Galelli, JF Wolfe, JL TI Degradation of antiflammin 2 under acidic conditions SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID LIPOCORTIN-I; ANTIINFLAMMATORY PEPTIDES; NONAPEPTIDE FRAGMENTS; UTEROGLOBIN; PHOSPHOLIPASE-A2; MECHANISM; AGGREGATION; INHIBITION; CLEAVAGE; REGION AB Antiflammin 2 (HDMNKVLDL, AF2) is a synthetic peptide derived from the region of highest sequence similarity of lipocortin I and uteroglobin, and is a potent antiinflammatory agent without any known side effects of corticosteroids. The antiinflammatoly activity of AF2 has been demonstrated, but is not reproducible between laboratories. It has been suggested that the chemical instability of this peptide is responsible for the loss of activity. The degradation of AF2 in aqueous solutions at a pH range of 3 to 10 has been reported. In this study, the degradation of AF2 at acidic pHs was monitored by reversed-phase HPLC. The reactions were studied as functions of buffer concentration and temperature. The rates of loss of AF2 followed apparent pseudo-first-order kinetics. Several products were isolated and identified by fast atom bombardment mass spectroscopy and tandem mass spectroscopy, and were the result of C- and N-terminus hydrolyses of aspartyl peptide bonds in AF2. The peptide bonds at C-termini of the aspartyl residues were most susceptible to hydrolysis, resulting in the formation of major degradation products, HDMNKVLD, MNKVLDL, and MNKVLD. The minor products from the N-terminus hydrolysis were HDMNKVL and MNKVL and formed at much slower rates. C1 UNIV TENNESSEE,DEPT PHARMACEUT SCI,MEMPHIS,TN 38163. NIH,WARREN G MAGNUSON CLIN CTR PHARM,PHARMACEUT DEV SECT,BETHESDA,MD 20892. NR 21 TC 5 Z9 5 U1 0 U2 0 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JUL PY 1996 VL 85 IS 7 BP 695 EP 699 DI 10.1021/js960006f PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA UW198 UT WOS:A1996UW19800006 PM 8818992 ER PT J AU Ishitani, R Kimura, M Sunaga, K Katsube, N Tanaka, M Chuang, DM AF Ishitani, R Kimura, M Sunaga, K Katsube, N Tanaka, M Chuang, DM TI An antisense oligodeoxynucleotide to glyceraldehyde-3-phosphate dehydrogenase blocks age-induced apoptosis of mature cerebrocortical neurons in culture SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CEREBELLAR GRANULE CELLS; RECEPTOR MESSENGER-RNA; SKELETAL-MUSCLE; PROTEIN; DEATH; TETRAHYDROAMINOACRIDINE; RAT; EXPRESSION; SURVIVAL; BINDING AB We recently reported that the age-induced apoptotic death of cultured cerebellar neurons is correlated with an increased expression of a particulate-bound 38-kDa protein that we identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). To determine whether this phenomenon of GAPDH overexpression occurs in other cell types, we selected primary cultures of cerebrocortical cells for testing, because under normal culture conditions, cortical neurons die progressively after 15 days in vitro. As with cerebellar neurons, this age-induced neuronal death involves ultrastructural changes and internucleosomal DNA fragmentation characteristic of apoptosis and is effectively prevented by actinomycin-D and cycloheximide. Moreover, a GAPDH antisense oligodeoxyribonucleotide arrested this cortical neuronal death for about 4 to 5 days and thus was more effective than cycloheximide. By contrast, its corresponding sense oligonucleotide had no effect. Additionally, the age-induced apoptosis of cortical neuronal cultures is effectively protected by aurintricarboxylic acid and tetrahydroaminoacridine (an antidementia drug). Before cell death, GAPDH mRNA levels increased by about 2-fold and the increase was blocked by the above-mentioned neuroprotective agents and the GAPDH antisense, but not sense, oligonucleotide. The effects of antisense oligonucleotide are more robust in the present case than those found with cerebellar neurons, and they indicate a significant, though at present not defined, role of GAPDH in the apoptotic process occurring in these two types of neurons. C1 ONO PHARMACEUT CO LTD,CHUO KU,OSAKA,JAPAN. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Ishitani, R (reprint author), JOSAI UNIV,GRP CELLULAR NEUROBIOL,SAKADO,SAITAMA 35002,JAPAN. NR 38 TC 77 Z9 79 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1996 VL 278 IS 1 BP 447 EP 454 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UW683 UT WOS:A1996UW68300055 PM 8764381 ER PT J AU Yoshimura, N White, G Weight, FF deGroat, WC AF Yoshimura, N White, G Weight, FF deGroat, WC TI Different types of Na+ and A-type K+ currents in dorsal root ganglion neurones innervating the rat urinary bladder SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID AFFERENT NEURONS; HORSERADISH-PEROXIDASE; POTASSIUM CURRENTS; SODIUM-CHANNELS; VOLTAGE-CLAMP; CELLS; TETRODOTOXIN; FIBERS; SUBPOPULATIONS; CAPSAICIN AB 1. Whole-cell patch-clamp recording in combination with axonal tracing techniques was used to examine the electrical properties of afferent neurones innervating the urinary bladder of the adult rat. Individual bladder afferent cells were labelled by Fast Blue (FB), injected into the bladder wall. 2. Passive and active electrical parameters at room temperature (20-22 degrees C) in FB-labelled bladder afferent neurones were comparable with those in unlabelled neurones. Unselected dorsal root ganglion (DRG) neurones as well as bladder afferent neurones exhibited two different types of action potential: high-threshold humped spikes in small-sized neurones and low-threshold narrow spikes in large-sized neurones. 3. The majority (70 %) of bladder neurones which were small in size expressed high-threshold tetrodotoxin (TTX)-resistant Na+ channels and slow-inactivating A-type K+ channels (K-A), which were available at the resting: membrane potential, whereas large-sized DRG: neurones had low-threshold TTX-sensitive Na+ channels and fast-inactivating K-A channels, which were almost completely inactivated at the resting membrane potential. 4. Half-maximal conductances of activation of TTX-resistant and TTX-sensitive Na+ currents were obtained at -10.3 and -25.3 mV, respectively. The TTX-resistant and TTX-sensitive Na+ currents were half-inactivated at -25.3 and -56 mV, respectively. 5. In the TTX-resistant neurones, the transient outward K+ current (A-type current, I-A) with half-maximal conductance at -40.8 mV was half-inactivated at -77.5 mV, and exhibited slower decaying kinetics (mean decay constant (tau), 240 ms) than the I-A current recorded from the large-sized TTX-sensitive neurones (mean tau, 20 ms). 6. These results suggest that the majority of bladder afferent neurones have high electrical thresholds for spike activation due to the TTX-resistant Na+ current and tile solw-inactivating I-A current, which reflect the large population of unmyelinated high-threshold C fibre afferents that innervate the urinary bladder. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,SECT ELECTROPHYSIOL,ROCKVILLE,MD 20892. RP Yoshimura, N (reprint author), UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,PITTSBURGH,PA 15261, USA. FU NIDDK NIH HHS [DK-49430] NR 41 TC 83 Z9 83 U1 0 U2 0 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 JUL 1 PY 1996 VL 494 IS 1 BP 1 EP 16 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UY428 UT WOS:A1996UY42800001 PM 8814602 ER PT J AU Chrousos, GP AF Chrousos, GP TI The hypothalamic-pituitary-adrenal axis and the female reproductive system SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Scientific Meeting of the Physiological-Society CY APR 16-18, 1996 CL UNIV COLL LONDON, LONDON, ENGLAND SP Physiol Soc HO UNIV COLL LONDON RP Chrousos, GP (reprint author), NICHHD,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 1996 VL 494P BP S11 EP S11 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VA341 UT WOS:A1996VA34100205 ER PT J AU Smith, JC AF Smith, JC TI The respiratory oscillator in mammals: Neurones, networks, and new models SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Scientific Meeting of the Physiological-Society CY APR 16-18, 1996 CL UNIV COLL LONDON, LONDON, ENGLAND SP Physiol Soc HO UNIV COLL LONDON RP Smith, JC (reprint author), NINCDS,NEURAL CONTROL LAB,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 1996 VL 494P BP S15 EP S16 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VA341 UT WOS:A1996VA34100210 ER PT J AU Yu, KF AF Yu, KF TI A simple comparison of two sequences of probabilities SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE risk difference; squared risk difference; squared distance; odds ratio; estimation; testing hypotheses ID STANDARDIZED RISK DIFFERENCES; CONTINGENCY-TABLES; ODDS RATIOS; TESTS AB A simple measure of comparison for two sequences of probabilities is proposed, It is the squared distance between these two sequences. An estimation procedure including a point estimator and a confidence interval is proposed for this simple measure. A testing procedure is presented for testing the difference of the two sequences. This new measure and the statistical procedures based on it have certain distinct advantages over the Mantel-Haenszel procedure in the situation where one sequence is not majorized by the other. A test which takes advantages of both the squared distance test and the Mantel-Haenszel test is proposed. Some simulation studies on these varieties are conducted. C1 NICHHD,BIOMETRY & MATH STAT BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,NIH,BETHESDA,MD 20892. NR 12 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 1 PY 1996 VL 52 IS 3 BP 271 EP 287 DI 10.1016/0378-3758(95)00132-8 PG 17 WC Statistics & Probability SC Mathematics GA UP771 UT WOS:A1996UP77100002 ER PT J AU Lahey, BB Flagg, EW Bird, HR SchwabStone, ME Canino, G Dulcan, MK Leaf, PJ Davies, M Brogan, D Bourdon, K Horwitz, SM RubioStipec, M Freeman, DH Lichtman, JH Shaffer, D Goodman, SH Narrow, WE Weissman, MM Kandel, DB Jensen, PS Richters, JE Regier, DA AF Lahey, BB Flagg, EW Bird, HR SchwabStone, ME Canino, G Dulcan, MK Leaf, PJ Davies, M Brogan, D Bourdon, K Horwitz, SM RubioStipec, M Freeman, DH Lichtman, JH Shaffer, D Goodman, SH Narrow, WE Weissman, MM Kandel, DB Jensen, PS Richters, JE Regier, DA TI The NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study: Background and methodology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE epidemiology; mental disorders; service utilization ID DSM-III DISORDERS; PSYCHIATRIC-DISORDERS; LARGE SAMPLE; PUERTO-RICO; PREVALENCE; POPULATION; HEALTH AB Objective: A collaborative study was conducted to develop methods for surveys of mental disorder and service utilization in unscreened population-based samples of children and adolescents. Method: Probability household samples of youths 9 through 17 years of age were selected at four sites and interviews were conducted with a total of 1,285 pairs of youths and their adult caretakers in their homes. Lay interviewers administered a computer-assisted version of the NIMH Diagnostic Interview Schedule for Children Version 2.3 and structured interviews to assess demographic variables, functional impairment, risk factors, service utilization, and barriers to service utilization. Results: More than 7,500 households were enumerated at four sites, with enumeration response rates above 99%. Across sites, 84% of eligible youth-caretaker pairs were interviewed for about 2 hours each. Ninety-five percent of both youths and caretakers found the interview to be acceptable enough to recommend to a friend. Conclusions: These findings indicate that large-scale epidemiological surveys of mental disorders and mental health service use involving lengthy interviews in the homes of unscreened population-based samples of youths and their adult caretakers are acceptable to the community and can achieve good response rates. The other reports in this Special Section address the reliability and validity of the various survey instruments and other key findings. C1 EMORY UNIV,ATLANTA,GA 30322. NORTHWESTERN UNIV,EVANSTON,IL 60208. COLUMBIA UNIV,NEW YORK,NY 10027. YALE UNIV,NEW HAVEN,CT 06520. UNIV PUERTO RICO,SAN JUAN,PR 00936. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. NIMH,BETHESDA,MD 20892. RP Lahey, BB (reprint author), UNIV CHICAGO,DEPT PSYCHIAT MC3077,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. OI Richters, John/0000-0002-6780-1828; Jensen, Peter/0000-0003-2387-0650; Weissman, Myrna/0000-0003-3490-3075 FU NIMH NIH HHS [U01 MH46717, U01 MH46718, U01 MH46725] NR 45 TC 160 Z9 161 U1 10 U2 17 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 855 EP 864 DI 10.1097/00004583-199607000-00011 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000011 PM 8768345 ER PT J AU Shaffer, D Fisher, P Dulcan, MK Davies, M Piacentini, J SchwabStone, ME Lahey, BB Bourdon, K Jensen, PS Bird, HR Canino, G Regier, DA AF Shaffer, D Fisher, P Dulcan, MK Davies, M Piacentini, J SchwabStone, ME Lahey, BB Bourdon, K Jensen, PS Bird, HR Canino, G Regier, DA TI The NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3): Description, acceptability, prevalence rates, and performance in the MECA study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE Diagnostic Interview Schedule for Children; diagnostic interview; scales; measurement; child psychiatric disorders; epidemiology; prevalence of psychiatric disorders ID ADOLESCENTS; CHILDHOOD; COMMUNITY AB Objective: To describe the NIMH Diagnostic Interview Schedule for Children (DISC) Version 2.3 and to provide data on its performance characteristics in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Method: Data were collected on the DISC-2.3 at four sites on 1,285 randomly selected children, aged 9 through 17 years, and their parents. Two hundred forty-seven of these child-parent pairs were reassessed on the DISC-2.3 by a clinician interviewer, 1 to 3 weeks later. Results: Administration time was approximately 1 hour and the interview was acceptable to more than 90% of subjects. The reliability of questions to parents assessing impairment and age of onset was generally good to acceptable for most diagnoses but was less satisfactory for the child interview. Using information from parent and child, the prevalence for any diagnosis ranged from 50.6 if no impairment criteria were required to 5.4 if a Global Assessment Scale score of 50 or less was necessary. The prevalence of anxiety disorders and anuresis was markedly reduced by requiring attributable impairment. Conclusions: The DISC-2 is a reliable and economical tool for assessing child psychopathology. Reliability of the DISC-P-2.3 is superior to that of the child DISC for most diagnoses but is least good for anxiety disorders. The 2.3 version of the instrument provides a significant improvement over earlier versions. C1 COLUMBIA UNIV,DIV CHILD & ADOLOSCENT PSYCHIAT,NEW YORK,NY. NORTHWESTERN UNIV,DEPT PSYCHIAT,CHICAGO,IL 60611. YALE UNIV,CTR CHILD STUDY,NEW HAVEN,CT 06520. UNIV CHICAGO,DEPT CHILD PSYCHIAT,CHICAGO,IL 60637. NIMH,DIV EPIDEMIOL & SERV RES,ROCKVILLE,MD 20857. NIMH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857. UNIV PUERTO RICO,SCH MED,BEHAV SCI RES INST,SAN JUAN,PR 00936. RP Shaffer, D (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,UNIT 78,722 W 168TH ST,NEW YORK,NY 10032, USA. RI Piacentini, John/C-4645-2011; OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [MH 278 87 0002, MH 278 89 0001, MH 36971] NR 40 TC 972 Z9 979 U1 10 U2 24 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 865 EP 877 DI 10.1097/00004583-199607000-00012 PG 13 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000012 PM 8768346 ER PT J AU SchwabStone, ME Shaffer, D Dulcan, MK Jensen, PS Fisher, P Bird, HR Goodman, SH Lahey, BB Lichtman, JH Canino, G RubioStipec, M Rae, DS AF SchwabStone, ME Shaffer, D Dulcan, MK Jensen, PS Fisher, P Bird, HR Goodman, SH Lahey, BB Lichtman, JH Canino, G RubioStipec, M Rae, DS TI Criterion validity of the NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE Diagnostic interview Schedule for Children; diagnosis; validity; epidemiology; assessment AB Objective: To examine the criterion validity of the NIMH Diagnostic Interview Schedule for Children (DISC) Version 2.3 in the NIMH Methods far the Epidemiology of Child and adolescent Mental Disorders (MECA) Study, using a design that permitted several comparisons of DISC-generated diagnoses with diagnoses based on clinician symptom ratings. Method: Two hundred forty-seven youths were selected from the 1,285 parent-youth pairs that constituted the four-site MECA sample. Subjects who screened positive for any of the five diagnostic areas under investigation in the validity study (attention-deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, depressive disorder, and the major anxiety disorders) were recruited, as well as a comparable number of screen negatives. Clinicians reinterviewed separately both the youth and the primary caregiver using the DISC followed by a clinical-style interview, and then they rated the presence of symptoms and impairment. Computer algorithms combined this information into diagnoses using comparable rules for both DISC and clinical rating diagnoses. Results: In general, the DISC showed moderate to good validity across a number of diagnoses. Conclusions: Results suggest some specific diagnostic areas in which further revision of the DISC is warranted. Three main sources of variability in DISC-clinician diagnostic agreement were evident over and above that due to the instrument itself, including (1) the informant used, (2) the algorithm applied in synthesizing symptom reports, and (3) the design of the validity comparison. C1 COLUMBIA UNIV, NEW YORK, NY USA. CHILDRENS MEM HOSP, CHICAGO, IL 60614 USA. NIMH, ROCKVILLE, MD 20857 USA. NORTHWESTERN UNIV, SCH MED, CHICAGO, IL USA. EMORY UNIV, ATLANTA, GA 30322 USA. UNIV CHICAGO, CHICAGO, IL 60637 USA. UNIV PUERTO RICO, SAN JUAN, PR 00936 USA. RP SchwabStone, ME (reprint author), YALE UNIV, CTR CHILD STUDY, POB 207900, 230 S FRONTAGE RD, NEW HAVEN, CT 06520 USA. OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [U01 MH46717, U01 MH46718, U01 MH46725] NR 23 TC 276 Z9 278 U1 10 U2 21 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 878 EP 888 DI 10.1097/00004583-199607000-00013 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000013 PM 8768347 ER PT J AU Leaf, PJ Alegria, M Cohen, P Goodman, SH Horwitz, SM Hoven, CW Narrow, WE VadenKiernan, M Regier, DA AF Leaf, PJ Alegria, M Cohen, P Goodman, SH Horwitz, SM Hoven, CW Narrow, WE VadenKiernan, M Regier, DA TI Mental health service use in the community and schools: Results from the four-community MECA study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE psychiatric disorders; child and adolescent mental health services ID DISORDERS; CHILDREN; ADOLESCENTS; PREVALENCE AB Objective: To describe the use of mental health and substance abuse services by children and adolescents as reported from the four community sites included in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Method: As part of the MECA survey, questions were developed to identify children and adolescents utilizing mental health and substance abuse services. Youths aged 9 through 17 years and a parent/caretaker were interviewed. Because the investigators had concerns about the capacities of the younger children in the study to describe their use of mental health services, more extensive questions were asked of parents than of youths. Results: The procedures developed by the MECA project identified patterns of service use that varied in the four communities surveyed. Agreement between reports of parents and youths regarding the use of mental health and substance abuse services showed substantial inconsistencies, similar to reports of psychiatric disorders. At three of the four sites, the majority of children meeting criteria for a psychiatric disorder and scoring 60 or less on the Children's Global Assessment Scale reported some mental health-related service in the previous year, although at two of the sites fewer than 25% of these youths were seen in the mental health specialty sector. Conclusion: Community surveys show great promise for monitoring the need for mental health and substance abuse services and for identifying patterns of use. C1 UNIV PUERTO RICO,SCH PUBL HLTH,SAN JUAN,PR 00936. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY. EMORY UNIV,DEPT PSYCHOL,ATLANTA,GA 30322. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. NIMH,DIV EPIDEMIOL & SERV RES,ROCKVILLE,MD 20857. ABT ASSOCIATES INC,BETHESDA,MD. RP Leaf, PJ (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,624 N BROADWAY,BALTIMORE,MD 21205, USA. FU NIMH NIH HHS [U01 MH46718, P50 MH 50204, U01 MH 46725] NR 22 TC 355 Z9 356 U1 10 U2 23 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 889 EP 897 DI 10.1097/00004583-199607000-00014 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000014 PM 8768348 ER PT J AU Giedd, JN Rapoport, JL Leonard, HL Richter, D Swedo, SE AF Giedd, JN Rapoport, JL Leonard, HL Richter, D Swedo, SE TI Case study: Acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE basal ganglia; magnetic resonance imaging; obsessive-compulsive disorder; pediatric autoimmune neuropsychiatric disorders ID DISORDER AB Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAs) may arise when antibodies directed against invading bacteria cross-react with basal ganglia structures, resulting in exacerbations of obsessive-compulsive disorder (OCD) or tic disorders. This is a report of severe worsening of obsessive-compulsive symptoms in an adolescent boy following infection with group A beta-hemolytic streptococci for whom serial magnetic resonance imaging scans of the brain were acquired to assess the relationship between basal ganglia size, symptom severity, and treatment with plasmapheresis. These data provide further support for basal ganglia-mediated dysfunction in OCD and the potential for immunological treatments in PANDAs patients. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR MSC 1600,BETHESDA,MD 20892, USA. 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 11 TC 94 Z9 94 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 913 EP 915 DI 10.1097/00004583-199607000-00017 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000017 PM 8768351 ER PT J AU Ross, RG Hommer, D Radant, A Roath, M Freedman, R AF Ross, RG Hommer, D Radant, A Roath, M Freedman, R TI Early expression of smooth-pursuit eye movement abnormalities in children of schizophrenic parents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE eye movements; smooth pursuit; schizophrenia; children; at-risk; endophenotype ID SCHIZOTYPAL PERSONALITY-DISORDER; QUANTITATIVE ASSESSMENT; TRACKING DYSFUNCTION; MONOZYGOTIC TWINS; DISCORDANT TWINS; VISUAL TRACKING; MONKEY; RELATIVES; FAMILY; MODEL AB Objective: Disordered smooth-pursuit eye movements (SPEM) and, specifically, small anticipatory saccades that disrupt SPEM have been hypothesized to be a marker of genetic vulnerability to schizophrenia. This study compares SPEM in children of schizophrenic parents with normally developing control children to assess whether SPEM abnormalities are also present in a subset of at-risk children. Method: With infrared oculography, SPEM was examined in 13 children of schizophrenic parents and 19 normally developing controls (aged 6 to 15 years). Measures of smooth-pursuit gain and root mean square error were used in addition to more specific measures of catch-up saccades and anticipatory saccades. Results: Children of schizophrenic parents differed from normally developing controls on gain and root mean square error, but not on catch-up saccades. Small anticipatory saccades were significantly more frequent in the at-risk group. The percentage of total eye movements due to anticipatory saccades identified 54% of the at-risk group (compared with none of the control group) as performing more than two standard deviations above (worse than) the control mean. Conclusions: The presence of increased anticipatory saccades is evidence for an oculomotor dysfunction that may be a phenotype of the genetic risk for schizophrenia, expressed years prior to the possible development of clinical illness. C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. NIAAA,BETHESDA,MD. UNIV WASHINGTON,SEATTLE,WA 98195. FU NIMH NIH HHS [MH15442, MH38321, MH44212] NR 53 TC 41 Z9 43 U1 3 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 941 EP 949 DI 10.1097/00004583-199607000-00022 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000022 PM 8768356 ER PT J AU Slavkin AF Slavkin TI A lifetime of motion: Temporomandibular joints SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 JUL PY 1996 VL 127 IS 7 BP 1093 EP 1098 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UX175 UT WOS:A1996UX17500028 ER PT J AU Humphreys, BL Hole, WT McCray, AT Fitzmaurice, JM AF Humphreys, BL Hole, WT McCray, AT Fitzmaurice, JM TI Planned NLMI/AHCPR large-scale vocabulary test: Using UMLS technology to determine the extent to which controlled vocabularies cover terminology needed for health care and public health SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB The National Library of Medicine (NLM) and the Agency for Health Care Policy and Research (AHCPR) are sponsoring a test to determine the extent to which a combination of existing health-related terminologies covers vocabulary needed in health information systems. The test vocabularies are the 30 that are fully or partially represented in the 1996 edition of the Unified Medical Language System (UMLS) Metathesaurus, plus three planned additions: the portions of SNOMED International not in the 1996 Metathesaurus, the Read Clinical Classification, and the Logical Observations Identifiers, Names, and Codes (LOINC) system. These vocabularies are available to testers through a special interface to the Internet-based UMLS Knowledge Source Server. The test will determine the ability of the test vocabularies to serve as a source of controlled vocabulary for health data systems and applications. It should provide the basis for realistic resource estimates for developing and maintaining a comprehensive ''standard'' health vocabulary that is based on existing terminologies. C1 US DEPT HHS,AGCY HLTH CARE POLICY & RES,ROCKVILLE,MD 20852. RP Humphreys, BL (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 13 TC 16 Z9 16 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 1996 VL 3 IS 4 BP 281 EP 287 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA UV434 UT WOS:A1996UV43400005 PM 8816351 ER PT J AU Ackerman, MJ AF Ackerman, MJ TI Build for future technology when building for the future: A lesson from the Visible Human Project SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material RP Ackerman, MJ (reprint author), NATL LIB MED,BLDG 38A-B1N-30,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 1996 VL 3 IS 4 BP 300 EP 301 PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA UV434 UT WOS:A1996UV43400007 ER PT J AU Abshire, MK Buzard, GS Shiraishi, N Waalkes, MP AF Abshire, MK Buzard, GS Shiraishi, N Waalkes, MP TI Induction of c-myc and c-jun proto-oncogene expression in rat L6 myoblasts by cadmium is inhibited by zinc preinduction of the metallothionein gene SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID CALCIUM CHANNELS; METAL CARCINOGENESIS; INDUCED GENOTOXICITY; BINDING-PROTEINS; LIVER-CELLS; HEAT-SHOCK; PROSTATE; GROWTH; ACTIVATION; TOXICITY AB Certain proto-oncogenes transfer growth regulatory signals from the cell surface to the nucleus. These genes often show activation soon after cells are exposed to mitogenic stimulation but can also be activated as a nonmitogenic stress response. Cadmium (Cd) is a carcinogenic metal in humans and rodents and, though its mechanism of action is unknown, it could involve activation of such proto-oncogenes. Metallothionein (MT), a metal-inducible protein that binds Cd, can protect against many aspects of Cd toxicity, including genotoxicity and possibly carcinogenesis. Thus, the effects of Cd on expression of c-myc and c-jun in rat L6 myoblasts, and the effect of preactivation of the MT gene by Zn treatment on such oncogene expression, were studied. MT protein levels were determined by the Cd-heme assay, and MT, c-myc, and c-jun mRNA levels were measured using oligonucleotide hybridization and standardized to beta-actin levels. Cd (5 beta M CdCl2 0-30 h) stimulated both c-myc and c-jun mRNA expression. An initial peak of activation of c-myc expression occurred 2 h after initiation of Cd exposure, and levels remained elevated throughout the assessment period. Zn pretreatment markedly reduced the activation of c-myc expression by Cd compared to cells not receiving Zn pretreatment. Cd treatment increased c-jun mRNA levels by up to 3.5-fold. Again, Zn pretreatment markedly reduced Cd-induced activation of c-jun expression as minimal increases occurred with Cd exposures of less than or equal to 1 h, but otherwise the Zn pretreatment prevented activation of c-jun. The Zn pretreatment elevated MT protein levels >5-fold over control at the point of Cd exposure, but Cd exposure did not further elevate these Zn-induced MT levels. Similarly, Zn pre treatment did not result in increased relative MT mRNA levels above Cd exposure alone at various time points after Cd exposure. Therefore, Zn pretreatment, possibly by providing elevated MT protein levels at the point of Cd exposure, inhibited the Cd-induced c-myc and c-jun proto-oncogene expression. The extent of Cd-induced proto-oncogene activation thus may be limited by the presence of cellular MT. C1 NCI,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,DIV BASIC SCI,FREDERICK,MD 21702. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NR 55 TC 48 Z9 50 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JUL PY 1996 VL 48 IS 4 BP 359 EP 377 DI 10.1080/009841096161258 PG 19 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UZ364 UT WOS:A1996UZ36400004 PM 8691507 ER PT J AU Walther, MM AF Walther, MM TI Diagnosis of primary renal cell carcinoma in left supraclavicular lymph node by chromosome analysis - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material RP Walther, MM (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1996 VL 156 IS 1 BP 172 EP 172 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA UQ317 UT WOS:A1996UQ31700055 ER PT J AU Schumann, G Qin, L Rein, A Natsoulis, G Boeke, JD AF Schumann, G Qin, L Rein, A Natsoulis, G Boeke, JD TI Therapeutic effect of Gag-nuclease fusion protein on retrovirus-infected cell cultures SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; STAPHYLOCOCCAL NUCLEASE; POLYACRYLAMIDE-GEL; RNA; SEQUENCES; VECTORS; EXPRESSION; PARTICLES; REGION; ASSAY AB Capsid-targeted viral inactivation is a novel protein-based strategy for the treatment of viral infections. Virus particles are inactivated by targeting toxic fusion proteins to virions, where they destroy viral components from within. We have fused Staphylococcus nuclease (SN) to the C-terminal end of Moloney murine leukemia virus Gag and demonstrated that expression of this fusion protein in chronically infected chicken embryo fibroblasts resulted in its incorporation into virions and subsequent inactivation of the virus particles by degradation of viral RNA. Release of particles incorporating Gag-SN fusion proteins into the extracellular milieu activates the nuclease and results in destruction of the virion from within. By comparing the effects of incorporated SN and SN*, an enzymatically inactive missense mutant form of SN, on the infectivity of virus particles, we have clearly demonstrated that nucleolytic activity is the antiviral mechanism. Expression of Gag-SN fusion proteins as a therapeutic agent causes a stable reduction of infectious titers by 20- to 60-fold. The antiviral effect of capsid-targeted viral inactivation in our model system, using both prophylactic and therapeutic approaches, suggests that a similar anti-human immunodeficiency virus strategy might be successful. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702. AVIGEN INC,ALAMEDA,CA 94501. NR 44 TC 22 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4329 EP 4337 PG 9 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000018 PM 8676455 ER PT J AU Shibata, R Siemon, C Cho, MW Arthur, LO Nigida, SM Matthews, T Sawyer, LA Schultz, A Murthy, KK Israel, Z Javadian, A Frost, P Kennedy, RC Lane, HC Martin, MA AF Shibata, R Siemon, C Cho, MW Arthur, LO Nigida, SM Matthews, T Sawyer, LA Schultz, A Murthy, KK Israel, Z Javadian, A Frost, P Kennedy, RC Lane, HC Martin, MA TI Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-INFECTION; GLYCOPROTEIN GP120; IMMUNIZATION; RECOMBINANT; PROTECTION; CELLS; RETROVIRUSES; PREVENTION; ANTIBODY; VACCINIA AB To test whether the protective effects of attenuated simian immunodeficiency virus vaccines in macaques were applicable to the human immunodeficiency virus type 1 (HIV-1)-chimpanzee system, two groups of animals, previously infected with HIV-1(IIIB) or HTV-1(SF2) were each challenged with a heterologous clade B virus, HIV-1(DH12). Following challenge, the parameters measured included virus isolation (from plasma, peripheral blood mononuclear cells, and lymph node tissue); quantitative DNA PCR using primers capable of distinguishing HIV-1(IIIB), HTV-1(SF2), and HIV-1(DH12), from one another; and serologic assays to monitor changes in binding and neutralizing antibodies. In contrast to an HTV-1-naive chimpanzee that rapidly became infected following the inoculation of HIV-1(DH12), the two chimpanzees previously infected with HIV-1(IIIB), resisted repeated and escalating inoculations of HTV-1(DH12), as monitored by virus isolation and PCR. The two animals previously infected with HIV-1(SF2) became infected with HIV-1(DH12), but in contrast to the case with the HIV-1-naive chimpanzee, no cell-free viral RNA was detected in the plasma by the branched DNA procedure and levels of peripheral blood mononuclear cell-associated viral DNA were reduced 35- to 50-fold. C1 NIAID,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,FREDERICK,MD. DUKE UNIV,SCH MED,DEPT SURG,DURHAM,NC 27706. SW FDN BIOMED RES,DEPT VIROL & IMMUNOL,SAN ANTONIO,TX 78284. COULSTON FDN,ALAMOGORDO,NM. UNIV OKLAHOMA,HLTH SCI CTR,DEPT MICROBIOL & IMMUNOL,OKLAHOMA CITY,OK 73190. NR 37 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4361 EP 4369 PG 9 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000022 PM 8676459 ER PT J AU Passarelli, AL Kovacs, GR Moss, B AF Passarelli, AL Kovacs, GR Moss, B TI Transcription of a vaccinia virus late promoter template: Requirement for the product of the A2L intermediate-stage gene SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT RNA-POLYMERASE; EXPRESSION SYSTEM; PURIFICATION; DNA; IDENTIFICATION; REPLICATION; TRANSLATION; SEQUENCE; VIRIONS; MUTANT AB Evidence is presented that a 26-kDa protein encoded by the vaccinia virus A2L open reading frame, originally shown to be one of three intermediate-stage genes that together can transactive late-stage gene expression in transfection assays (J. G. Keck, C. J. Baldick, and B. bless, Cell 61:801-809, 1990), is required for in vitro transcription of a template with a late promoter, The critical step in this analysis was the preparation of an extract containing all the required factors except for the A2L protein, This extract was prepared from cells infected with a recombinant vaccinia virus expressing the bacteriophage T7 RNA polymerase in the presence of the DNA synthesis inhibitor cytosine arabinoside and transfected,vith plasmids containing the two other known transactivator genes, ALL and G8R, under T7 promoter control, Reaction mixtures made with extracts of these cells had background levels of late transcription activity, unless they were supplemented with extracts of cells transfected with the A2L gene, Active transcription mixtures were also made by mixing extracts from three sets of cells, each transfected with a gene (A1L, A2L, or G8R) encoding a separate factor, indicating the absence of any requirement for their coexpression, To minimize the possibility that the A2L protein Functions indirectly by activating another viral or cellular protein, this gene was expressed in insect cells by using a baculovirus vector, The partially purified recombinant protein complemented the activity of A2L-deficient cell extracts, Recombinant A1L, A2L, and G8R proteins, all produced in insect cells, together complemented extracts from mammalian cells containing only viral early proteins, concordant with previous in vivo transfection data. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 42 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4444 EP 4450 PG 7 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000031 PM 8676468 ER PT J AU Barsov, EV Huber, WE Marcotrigiano, J Clark, PK Clark, AD Arnold, E Hughes, SH AF Barsov, EV Huber, WE Marcotrigiano, J Clark, PK Clark, AD Arnold, E Hughes, SH TI Inhibition of human immunodeficiency virus type 1 integrase by the Fab fragment of a specific monoclonal antibody suggests that different multimerization states are required for different enzymatic functions SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ESCHERICHIA-COLI; RETROVIRAL DNA; HIV-1 INTEGRASE; PROTEIN INVITRO; INTRACELLULAR EXPRESSION; RECOMBINANT PROTEINS; IDENTIFICATION; BINDING; CLEAVAGE AB We have characterized a murine monoclonal antibody (MAb 35), which ass raised against human immunodeficiency virus type 1 (HIV-1) integration protein (IN), and the corresponding Felt 35. Although MAb 35 does not inhibit HIV-l IN, Fab 35 does. MAb 35 !and Fab 35) binds to an epitope in the C-terminal region of HIV-1 IN, Fab 35 inhibits 3'-end processing, strand transfer, and disintegration; however, DNA binding is not affected. The available data suggest that Fab 35 inhibits enzymatic activities of IN by interfering with the ability of IN to form multimers that are enzymatically active. This implies that the C-terminal region of HIV-1 IN participates in interactions that are essential for the multimerization of IN, Titration of the various IN-mediated enzymatic activities suggests that different degrees of multimerization are required for different activities of HIV-1 IN. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, FREDERICK, MD 21702 USA. RUTGERS STATE UNIV, DEPT CHEM, PISCATAWAY, NJ 08854 USA. CTR ADV BIOTECHNOL & MED, PISCATAWAY, NJ 08854 USA. RI Marcotrigiano, Joseph /K-6697-2016 OI Marcotrigiano, Joseph /0000-0003-0346-3353 NR 55 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4484 EP 4494 PG 11 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000036 PM 8676473 ER PT J AU Berthold, E Maldarelli, F AF Berthold, E Maldarelli, F TI cis-acting elements in human immunodeficiency virus type 1 RNAs direct viral transcripts to distinct intranuclear locations SO JOURNAL OF VIROLOGY LA English DT Article ID REV GENE-PRODUCT; ENV MESSENGER-RNA; TARGET SEQUENCE; FUNCTIONAL-ANALYSIS; PROTEIN EXPRESSION; TRANS-ACTIVATOR; NUCLEAR-RNA; HIV-1 LTR; LOCALIZATION; REGION AB Two distinct intranuclear locations were identified for alternatively spliced RNA transcripts expressed from the pNL4-3 infectious molecular clone of human immunodeficiency virus (HIV) type 1. Multiply spliced HIV RNA encoding tat was detected within the nucleus in large clusters; immunostaining and colocalization studies using laser-scanning confocal microscopy revealed that these structures contained the non-small nuclear ribonucleoprotein RNA processing factor, SC35. In contrast, unspliced gag RNA was detected in much smaller granules distributed throughout the nucleus, with little or no association with SC35-containing granules, Analyses of nuclear RNA expressed from recombinant plasmids encoding gag (pCMVgag-2) alone or tat (pCMVtat-2) alone revealed distributions corresponding to those obtained with pNL4-3, indicating that expression within the context of the HIV provirus was not required for the distinct RNA locations detected for these transcripts. The presence of unspliced gag RNA in small granules was confirmed in infections of H9 T-lymphocytic cells, indicating that gag localization was not restricted to transient expression systems. The intranuclear distribution of gag RNA was dependent on specific RNA sequences. Deletion of a portion of the gag gene of pCMVgag-2, containing a cis-repressing inhibitory region, resulted in redirection of unspliced gag RNA from small granules into large SC35-containing clusters. The addition of the Rev-responsive element, RRE, to the deleted pCMVgag-2 construct resulted in RNA transcripts which were no longer associated with SC35. We also identified a cellular intron, rabbit beta-globin-intervening sequence 2 (IVS-2) which, when introduced into pCMVgag2, redirected unspliced gag RNA into SC35-containing granules and permitted rev-independent Gag expression, These findings suggest that redirecting intranuclear RNA localization may influence gene expression, Color micrographs from this article are available for view at http parallel to 128.231.216.2/lmmhome.htm. C1 NIAID,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 76 TC 31 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 JUL PY 1996 VL 70 IS 7 BP 4667 EP 4682 PG 16 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000056 PM 8676493 ER PT J AU Zheng, ZM He, PJ Baker, CC AF Zheng, ZM He, PJ Baker, CC TI Selection of the bovine papillomavirus type 1 nucleotide 3225 3' splice site is regulated through an exonic splicing enhancer and its juxtaposed exonic splicing suppressor SO JOURNAL OF VIROLOGY LA English DT Article ID PRE-MESSENGER-RNA; PREMESSENGER RNA; POLYPYRIMIDINE TRACT; SNRNP BINDING; SR-PROTEINS; U2 SNRNP; SEQUENCES; INVITRO; DROSOPHILA AB Alternative splicing is an important mechanism for the regulation of bovine papillomavirus type 1 (BPV-1) gene expression during the virus life cycle. However, one 3' splice site, located at nucleotide (nt) 3225, is used for the processing of most BPV-1 pre-mRNAs in BPV-l-transformed C127 cells and at early to intermediate times in productively infected warts. At late stages of the viral life cycle, an alternative 3' splice site at nt 3605 is used for the processing of the late pre-mRNA. In this study, we used in vitro splicing in HeLa cell nuclear extracts to identify cis elements which regulate BPV-1 3' splice site selection. Two purine-rich exonic splicing enhancers were identified downstream of nt 3225, These sequences, designated SE1 (nt 3256 to 3305) and SE2 (nt 3477 to 3526), were shown to strongly stimulate the splicing of a chimeric Drosophila doublesex pre mRNA, which contains a weak 3' splice site. A BPV-1 late pre-mRNA containing the nt 3225 3' splice site but lacking both SE1 and SE2 was spliced poorly, indicating that this 3' splice site is inherently weak Analysis of the 3' splice site suggested that this feature is due to both a nonconsensus branch point sequence and a suboptimal polypyrimidine tract. Addition of SE1 to the late pre-mRNA dramatically stimulated splicing, indicating that SE1 also functions as an exonic splicing enhancer in its normal context. However, a late pre-mRNA containing both SE1 and SE2 as well as the sequence in between was spliced inefficiently. Further mapping studies demonstrated that a 48-nt pyrimidine-rich region immediately downstream of SE1 was responsible for this suppression of splicing. Thus, these data suggest that selection of the BPV-1 nt 3225 3' splice site is regulated by both positive and negative exonic sequences. C1 NCI,DIV BASIC SCI,TUMOR VIRUS BIOL LAB,NIH,BETHESDA,MD 20892. NR 67 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4691 EP 4699 PG 9 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000058 PM 8676495 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 SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR-TRANSFORMATION; DNA; INHIBITION; GENE; INTEGRATION; REPLICATION; SITE; AAV AB Rep68 protein, encoded by adeno-associated virus type 2 (AAV), has been previously shown to bind to specific sequences within the viral genome and in human chromosome 19. The effect of AAV Rep protein on human cellular genes is of interest because AAV is being developed as a gene therapy vector. We have identified sequences related to the Rep recognition sequence in the AAV P-5 promoter in or near the c-sis proto-oncogene and the genes coding for a hepatocyte glucose transporter, alpha-A-crystallin, and carcinoma marker GA733-1, The ability of Rep68 to bind to these sites was established by gel shift assays, and the effect of Rep68 on the expression of these genes was tested by semiquantitative reverse transcriptase PCR, Rep68 enhances the expression of the cais proto-oncogene, which codes for the B polypeptide of platelet-derived growth factor, a multifunctional growth factor that is involved in embryonic development, tissue regeneration, osteogenesis, fibrosis, atherosclerosis, and neoplasia. C1 NIDDK,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NR 30 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4783 EP 4786 PG 4 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000070 PM 8676507 ER PT J AU Hasenkrug, KJ Robertson, SJ Portis, J McAtee, F Nishio, J Chesebro, B AF Hasenkrug, KJ Robertson, SJ Portis, J McAtee, F Nishio, J Chesebro, B TI Two separate envelope regions influence induction of brain disease by a polytropic murine retrovirus (FMCF98) SO JOURNAL OF VIROLOGY LA English DT Article ID LEUKEMIA-VIRUS-TB; CENTRAL NERVOUS-SYSTEM; LONG TERMINAL REPEAT; FOCUS-INDUCING VIRUS; C RNA VIRUS; PARALYTOGENIC MUTANT; TEMPERATURE SENSITIVITY; NEUROTROPIC RETROVIRUS; CELL TROPISM; TS1 AB The major determinants involved in neurological disease induction by polytropic murine leukemia virus FMCF98 are encoded by the envelope gene. To map these determinants further, we produced four chimeras which contained neurovirulent FMCF98 envelope sequences combined with envelope sequences from the closely related nonneurovirulent polytropic virus FMCF54, Surprisingly, two chimeric viruses containing completely separate envelope regions from FMCF98 could both induce neurological disease, Clinical signs caused by both neurovirulent chimeras appeared to be indistinguishable from those caused by FMCF98, although the incubation periods were longer. One neurovirulence determinant mapped to the N-terminal portion of gp70, which contains the VRA and VRB receptor-binding regions, while the other determinant mapped downstream of both of the variable regions. Western blot (immunoblot) analyses and immunohistochemical staining of tissue sections indicated that the variations in neurovirulence of these viruses could not be explained by differences in either the quantitative level or the location of virus expression in the brain. RP Hasenkrug, KJ (reprint author), NIAID,NIH,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 31 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1996 VL 70 IS 7 BP 4825 EP 4828 PG 4 WC Virology SC Virology GA UR130 UT WOS:A1996UR13000079 PM 8676516 ER PT J AU Young, Y German, P Brant, L Kenzora, J Magaziner, J AF Young, Y German, P Brant, L Kenzora, J Magaziner, J TI The predictors of surgical procedure and the effects on functional recovery in elderly with subcapital fractures SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HIP FRACTURE; EXPERIENCE AB Background. it has been demonstrated that the majority of hip fracture patients do not regain their prefracture level of functioning and usually decline in function following fracture. Little is known about the effectiveness of surgical procedure performed (hemiarthroplasty vs internal fixation) on functional recovery of subcapital fracture patients. This study examines the factors related to the type of the surgical procedure chosen and the effect of this selection on physical activities of daily living (PADL) and instrumental activities of daily living (IADL). Methods. The sample consists of 312 patents with subcapital fractures age 65 and older admitted from the community to one of seven Baltimore area hospitals between 1984 and 1986. Baseline information was obtained during hospitalization through structured interviews with both patients and their significant others (proxy). The follow-up interviews were administered to proxies at two months, six months, and one year after discharge from hospital. Information on disease diagnoses, fracture severity, and surgical procedures performed was obtained from medical charts. Results. Patients with a displaced fracture were seven more times likely to receive a hemiarthroplasty (OR = 7.0, 95% Cl 3.7-13.1). During the short-term recovery (2 months after surgery), patients who received hemiarthroplasty were doing better in transferring, meal preparation, and shopping than those who received internal fixation. For the long-term functional recovery (one year), the overall PADL and IADL functions were not statistically significantly different between the two surgical procedures performed. Conclusions. The severity of fracture was found to be the most important determinant of surgical procedure. Patients with a subcapital fracture who received hemiarthroplasty tended to have a better functional recovery in the short term. Further study of other benefits of using a hemiarthroplasty is needed. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. NIA,BALTIMORE,MD 21224. RP Young, Y (reprint author), UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,DIV GERONTOL,660 W REDWOOD ST,142,BALTIMORE,MD 21201, USA. FU AHRQ HHS [R01 HSO6658]; NIA NIH HHS [AG06322]; NICHD NIH HHS [HD0073] NR 26 TC 17 Z9 17 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1996 VL 51 IS 4 BP M158 EP M164 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VN556 UT WOS:A1996VN55600012 PM 8680998 ER PT J AU Omori, N Evarts, RP Omori, M Hu, ZY Marsden, ER Thorgeirsson, SS AF Omori, N Evarts, RP Omori, M Hu, ZY Marsden, ER Thorgeirsson, SS TI Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat SO LABORATORY INVESTIGATION LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; STEM-CELL FACTOR; EPITHELIAL-CELLS; MESSENGER-RNA; FACTOR-ALPHA; FACTOR LIF; MOLECULAR-CLONING; PRIMARY CULTURE; INTERLEUKIN-6; DIFFERENTIATION AB Leukemia inhibitory factor (LIF) is a polyfunctional cytokine that was discovered in the conditioned medium from Buffalo rat liver cells. In the liver, LIF is known to induce acute phase proteins in the hepatocytes. No comprehensive study has yet been performed on the physiological role of this cytokine during liver regeneration. Thus, we studied the level of expression and cellular distribution of transcripts for LIF, its receptor (LIFR), and signal transducing subunit gp130 during rat liver regeneration after both simple partial hepatectomy (PH) and the oval cell activation induced by the combination of 2-acetylaminofluorene and PH. In addition, the expression of an acute phase protein alpha 1-acidglycoprotein was examined. The level of transcripts for LIF and its receptor subunits increased and remained elevated during oval cell expansion. In contrast, after PH, the transcripts were induced only transiently, showing a peak 24 hours after the operation. LIF and receptor subunits were expressed in both parenchymal and nonparenchymal fractions in the 2-acetylaminoiluorene/PH model, but the level of expression was most pronounced in the nonparenchymal fraction. In situ hybridization clearly revealed a strong expression of LIF, LIFR, and gp130 in the oval cells and demonstrated only a weak expression in the parenchyma. Interestingly, transcripts of alpha 1-acidglycoprotein were exclusively detected in the parenchyma. These results suggest a phenotypic difference between oval cells and hepatocytes in their signaling through gp130. We hypothesize that the LIF/LIFR gp130 system may be involved in the expansion and differentiation of the liver stem cell compartment. C1 NCI, EXPTL CARCINOGENESIS LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NR 55 TC 63 Z9 66 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 1996 VL 75 IS 1 BP 15 EP 24 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA UY602 UT WOS:A1996UY60200002 PM 8683936 ER PT J AU Beckner, ME Liotta, LA AF Beckner, ME Liotta, LA TI AAMP, a conserved protein with immunoglobulin and WD40 domains, regulates endothelial tube formation in vitro SO LABORATORY INVESTIGATION LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN PARTICLE; FIBROBLAST GROWTH-FACTORS; CELL-ADHESION MOLECULE; YEAST CHROMOSOME-III; BETA-SUBUNITS; SACCHAROMYCES-CEREVISIAE; BINDING-PROTEIN; NEGATIVE REGULATOR; GAMMA-SUBUNITS; GENE AB Angio-associated migratory cell protein (AAMP) is a newly discovered protein that is widely distributed with strong expression in endothelial cells and others with migratory potential (cytotrophoblasts, carcinoma cells, etc). AAMP is 52 kd with an isoelectric point of 5.2. Its sequence contains immunoglobulin type domains, WD40 repeats, a large acidic region with an acid box, a potential transmembrane region, potential serine/threonine phosphorylation sites, and a positively charged amino-terminal region with strong heparin binding potential (K-d = 14 pmol). Human umbilical vein endothelial cells cultured on Matrigel, a basement membrane material, form endothelial tubes (capillary-like structures). Anti-recombinant AAMP (anti-rAAMP) (1 to 10 mu g/ml) inhibits this process under conditions that favor cross-linking of its ligand (AAMP). Immunofluorescent staining has shown that AAMP is distributed both intracellularly and extracellularly in cultures of endothelial cells and tubes. Molecular analysis of AAMP's protein sequence shows a striking evolutionary relationship with the YCR072c protein in Saccharyomyces cerevisiae. Both the human and yeast proteins show an unusual and almost identical arrangement of immunoglobulin type domains, WD40 repeats, a protein kinase C phosphorylation consensus site in the carboxyl region, and a positively charged amino-terminal region that in AAMP has heparin binding potential. Detection of YCR072c's immunoglobulin type domains is new. Thus, AAMP is a protein that has been highly conserved in evolution and may function in the regulation of endothelial tube formation. RP Beckner, ME (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,ROOM 2A-33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 15 Z9 15 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 JUL PY 1996 VL 75 IS 1 BP 97 EP 107 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA UY602 UT WOS:A1996UY60200010 PM 8683944 ER PT J AU Raine, CS Wu, E Ivanyi, J Katz, D Brosnan, CF AF Raine, CS Wu, E Ivanyi, J Katz, D Brosnan, CF TI Multiple sclerosis: A protective or a pathogenic role for heat shock protein 60 in the central nervous system? SO LABORATORY INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; T-CELL RECEPTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CULTURED MOUSE OLIGODENDROCYTES; MYELIN BASIC-PROTEIN; GAMMA-DELTA; STRESS-PROTEIN; AUTOIMMUNE DEMYELINATION; MYCOBACTERIAL 65-KDA; EXPRESSION AB The stress proteins belonging to the heat shock protein 60 (hsp60) family of molecular chaperones with known immunogenic properties are expressed at increased levels in a number of autoimmune conditions. Because previous studies from this laboratory suggested that hsp60 may be involved in the pathogenesis of the chronic multiple sclerosis (MS) plaque, we have examined autopsied central nervous system tissue from 10 cases of MS, ranging in clinical history from acute to chronic inactive. MS lesions ranged from acute, actively demyelinating and edematous, to fibrous astrogliotic and chronically demyelinated. As controls, central nervous system tissue from other neurologic diseases and nonneurologic conditions was used. Frozen, paraffin, and epoxy-embedded sections were studied immunocytochemically with the ML30 mAb to hsp60. Acute MS lesions displayed the greatest reactivity, with particularly prominent staining of hypertrophic astrocytes, reactive macrophages, and hyperplastic oligodendrocytes. In all these cells, elevated expression occurred in the constitutive site for hsp60 (mitochondria) and within the cytosol, which is suggestive of a shift in expression. The hsp60-reactive oligodendrocytes were structurally intact. Chronic active MS lesions also revealed the highest levels of hsp60 in hypertrophic astrocytes and oligodendrocytes. Chronic silent MS lesions displayed elevated hsp60 in hypertrophic astrocytes only while constitutive expression occurred elsewhere in the central nervous system at levels slightly higher than normal. Other neurologic disease tissue displayed expression elevated above that found in nonneurologic cases, but this was considerably less than that seen in acute MS. Of the other neurologic diseases, AIDS encephalitis revealed the greatest activity for hsp80, with both mitochondrial and cytosolic staining of astrocytes. It is proposed that the high levels of hsp60 in hyperplastic, structurally intact oligodendrocytes in acute MS lesions may bespeak a protective mechanism, whereas hsp80 in chronic active lesions may serve a pathogenic role in the later depletion of these cells. C1 ALBERT EINSTEIN COLL MED, DEPT PATHOL, BRONX, NY 10461 USA. ALBERT EINSTEIN COLL MED, DEPT NEUROL, BRONX, NY 10461 USA. ALBERT EINSTEIN COLL MED, DEPT NEUROSCI, BRONX, NY 10461 USA. ALBERT EINSTEIN COLL MED, ROSE F KENNEDY CTR RES MENTAL RETARDAT & HUMAN DE, BRONX, NY 10461 USA. HAMMERSMITH HOSP, MRC, CTR CLIN SCI, LONDON, ENGLAND. NCI, OFF CLIN DIRECTOR, NINDS, PATHOL LAB, BETHESDA, MD 20892 USA. FU NINDS NIH HHS [NS11920, NS08952, NS31919] NR 59 TC 29 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 1996 VL 75 IS 1 BP 109 EP 123 PG 15 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA UY602 UT WOS:A1996UY60200011 PM 8683935 ER PT J AU Lalwani, AK Mhatre, AN SanAgustin, TB Wilcox, ER AF Lalwani, AK Mhatre, AN SanAgustin, TB Wilcox, ER TI Genotype-phenotype correlations in type 1 Waardenburg syndrome SO LARYNGOSCOPE LA English DT Article ID HUP2 PAIRED DOMAIN; SYNDROME TYPE-I; HUMAN HOMOLOG; MUTATIONS; GENE; PAX-3; HETEROGENEITY; HOMEODOMAIN; PROTEIN; SPLOTCH AB Type 1 Waardenburg syndrome (WS1) is an autosomal dominant disorder characterized by dystopia canthorum, sensorineural deafness, and pigmentary disturbances, Previous work has linked the disease to PAX3, a transcription factor with two highly conserved DNA binding motifs: a paired box and a homeobox, Several mutations within the paired box of PAX3 have been reported. We have identified the first two mutations within the homeobox in two different families. Herein, we report the phenotypic expression of WS1 in these two families and explore the implications for possible genotype-phenotype correlations. The phenotypic expression was variable within and between the families. Sensorineural hearing loss was present in 71% of affected individuals. Spectrum of hearing loss included unilateral high frequency (>4000 Hz), profound unilateral hearing loss, and bilateral profound hearing loss, The severity of hearing impairment varied significantly within and among families. Phenotypically, these two WS1 families with mutations within the PAX3 homeobox could not be differentiated from those families with paired box mutations. More precise genotype/phenotype correlation may be possible when additional mutations are described throughout the PAX3 gene. C1 NIDCD,MOLEC GENET LAB,NIH,BETHESDA,MD. RP Lalwani, AK (reprint author), UNIV CALIF SAN FRANCISCO,DEPT OTOLARYNGOL HEAD & NECK SURG,LAB MOL OTOL,350 PARNASSUS AVE,SAN FRANCISCO,CA 94117, USA. NR 25 TC 6 Z9 6 U1 0 U2 1 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 1996 VL 106 IS 7 BP 895 EP 902 DI 10.1097/00005537-199607000-00021 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UW659 UT WOS:A1996UW65900021 PM 8667990 ER PT J AU Lukszo, J Patterson, D Albericio, F Kates, SA AF Lukszo, J Patterson, D Albericio, F Kates, SA TI 3-(1-Piperidinyl)alanine formation during the preparation of C-terminal cysteine peptides with the Fmoc/t-Bu strategy SO LETTERS IN PEPTIDE SCIENCE LA English DT Article DE cysteine; C-terminus; MALDI-TOF; 3-(1-piperidinyl)alanine; side reaction ID SOLID-PHASE SYNTHESIS; COUPLING REAGENTS; SUPPORTS; ACETAMIDOMETHYL; RACEMIZATION; ACIDS AB Several side reactions have been detected for cysteine-containing peptides. During the synthesis of C-terminal cysteine peptides, a base-catalyzed elimination of the sulfhydryl-protected side-chain to afford the dehydroalanine derivative followed by a nucleophilic addition to the alkene was observed. MALDI-TOF analysis was a useful analytical technique to determine this phenomenon. C1 PERSEPT BIOSYST INC, FRAMINGHAM, MA 01701 USA. UNIV BARCELONA, DEPT ORGAN CHEM, E-08028 BARCELONA, SPAIN. NIAID, PEPTIDE SYNTH & ANAL LAB, NIH, LMS, ROCKVILLE, MD 20852 USA. OI Albericio, Fernando/0000-0002-8946-0462 NR 38 TC 36 Z9 36 U1 2 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PD JUL PY 1996 VL 3 IS 3 BP 157 EP 166 DI 10.1007/BF00132978 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE922 UT WOS:A1996VE92200007 ER PT J AU Booth, SL Pennington, JAT Sadowski, JA AF Booth, SL Pennington, JAT Sadowski, JA TI Dihydro-vitamin K-1: Primary food sources and estimated dietary intakes in the American diet SO LIPIDS LA English DT Article ID PHYLLOQUINONE CONTENT AB Dihydro-vitamin K-1 was recently identified as a dietary form of vitamin K produced during the hydrogenation of vitamin K-1-rich vegetable oils. Dihydro-vitamin K-1 is absorbed, with measurable levels in human plasma following dietary intake. To determine the primary food sources of dihydro-vitamin K-1 in the American diet, 261 foods from the U.S. Food and Drug Administration's (FDA) Total Diet Study (TDS) were analyzed by high-performance liquid chromatography. Of these foods, 36 contained dihydro-vitamin K-1. Fast-food items that were otherwise poor sources of vitamin K-1, such as french fries and fried chicken, contained appreciable amounts of dihydro-vitamin K-1 (36 and 18 mu g/100 g, respectively). These nutrient values were then applied to the FDA TDS consumption model to determine average dietary intake of dihydro-vitamin K-1 in 14 age-gender groups. With the exception of infants, all age-gender groups had estimated mean daily dihydro-vitamin K-1 intakes of 12-24 mu g, compared to mean daily vitamin K-1 intakes of 24-86 mu g. The vitamin K-1 and dihydro-vitamin K-1 intakes were summed, and the dietary contribution of dihydro-vitamin K-1 was expressed as a percentage of total vitamin K intake. Children reported the highest intakes of dihydro-vitamin K-1 (30% of total vitamin K intake), followed by a progressive decrease in percentage contribution with age. There are currently no data on the relative bioavailability of dihydro-vitamin K-1 but, given its abundance in the American diet, this hydrogenated form of vitamin K warrants further investigation. C1 TUFTS UNIV,JEAN MAYER USDA HUMAN NUTR RES CTR AGING,VITAMIN K LAB,BOSTON,MA 02111. NIH,DIV NUTR RES COORDINAT,BETHESDA,MD 20892. NR 21 TC 29 Z9 30 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD JUL PY 1996 VL 31 IS 7 BP 715 EP 720 DI 10.1007/BF02522887 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UW656 UT WOS:A1996UW65600004 PM 8827694 ER PT J AU Vymazal, J Zak, O Bulte, JWM Aisen, P Brooks, RA AF Vymazal, J Zak, O Bulte, JWM Aisen, P Brooks, RA TI T-1 and T-2 of ferritin solutions: Effect of loading factor SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ferritin; iron; relaxometry; relaxation enhancement ID DIFFERENT FIELD STRENGTHS; BRAIN IRON; MR; CONTRAST; T2; SUSCEPTIBILITY; DEPENDENCE; PARKINSON; DIFFUSION; DISEASE AB Proton magnetic relaxation times T-1 and T-2 were measured at field strengths from 0.05 T to 1.5 T in solutions of ferritin with loading factors from 90 to 3600 iron atoms per molecule, 1/T-2 increased linearly with field strength, as previously observed, and the slope per unit iron was approximately the same in all samples, This latter finding indicates that the field dependence of T-2 may be used as a measure of ferritin-bound iron, regardless of loading factor, A possible explanation is presented, based on the presumed antiferromagnetic structure of the ferritin core and the linear dependence of 1/T-2 on core magnetization, A nonzero contribution to 1/T-2 in the limit of tow field and a contribution to 1/T-1 were also found, both of which increase linearly with loading factor for constant protein concentration; these effects represent quantum mechanical dipole-dipole relaxation of water protons either by iron atoms on the surface of the core or by the iron core itself, Finally, the extrapolated intercept at LF = 0 for both 1/T-1, and 1/T-2 indicates a contribution from a small number of iron ions bound to the protein shell, These results may help in the use of MRI to measure brain iron and possibly even ferritin loading factor. C1 NINCDS, NEUROIMAGING BRANCH, NATL INST HLTH, BETHESDA, MD 20892 USA. NATL INST HLTH, LAB DIAGNOST RADIOL RES, BETHESDA, MD USA. ALBERT EINSTEIN COLL MED, DEPT PHYSIOL & BIOPHYS, BRONX, NY 10467 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 43 TC 67 Z9 67 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 1996 VL 36 IS 1 BP 61 EP 65 DI 10.1002/mrm.1910360111 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT368 UT WOS:A1996UT36800010 PM 8795021 ER PT J AU Lyu, MS Park, DJ Rhee, SG Kozak, CA AF Lyu, MS Park, DJ Rhee, SG Kozak, CA TI Genetic mapping of the human and mouse phospholipase C genes SO MAMMALIAN GENOME LA English DT Article ID LEUKEMIA-VIRUS RECEPTOR; CHROMOSOMAL LOCATION; ELEVATED CONTENT; CLONING; EXPRESSION; LOCALIZATION; C-GAMMA-1; SEQUENCE; CELLS; PURIFICATION AB To determine chromosome positions for 10 mouse phospholipase C (PLC) genes, we typed the progeny of two sets of genetic crosses for inheritance of restriction enzyme polymorphisms of each PLC. Four mouse chromosomes, Chr 1, 11, 12, and 19, contained single PLC genes. Four PLC loci, Plcb1, Plcb2, Plcb4, and Plcg1, mapped to three sites on distal mouse Chr 2. Two PLC genes, Plcd1 and Plcg2, mapped to distinct sites on Chr 8. We mapped the human homologs of eight of these genes to six chromosomes by analysis of human x rodent somatic cell hybrids. The map locations of seven of these genes were consistent with previously defined regions of conserved synteny; Plcd1 defines a new region of homology between human Chr 3 and mouse Chr 8. C1 NIAID,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. NHLBI,LAB SIGNAL TRANSDUCT,NIH,BETHESDA,MD 20892. RI Park, Do-Joon/J-2736-2012 NR 45 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1996 VL 7 IS 7 BP 501 EP 504 DI 10.1007/s003359900151 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UZ385 UT WOS:A1996UZ38500005 PM 8672127 ER PT J AU Krebsbach, PH Yamada, Y AF Krebsbach, PH Yamada, Y TI Untitled SO MATRIX BIOLOGY LA English DT Letter RP Krebsbach, PH (reprint author), NIDR,DEV BIOL LAB,BLDG 30,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD JUL PY 1996 VL 15 IS 2 BP 64 EP 64 DI 10.1016/S0945-053X(96)90142-0 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX919 UT WOS:A1996UX91900002 PM 8837004 ER PT J AU Sallis, JF Strikmiller, PK Harsha, DW Feldman, HA Ehlinger, S Stone, EJ Williston, J Woods, S AF Sallis, JF Strikmiller, PK Harsha, DW Feldman, HA Ehlinger, S Stone, EJ Williston, J Woods, S TI Validation of interviewer- and self-administered physical activity checklists for fifth grade students SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE measurement; self-report; validity; children; physical activity; epidemiology ID HEART-RATE; CHILDREN; RELIABILITY; ADOLESCENTS; FITNESS; MONITOR AB The purpose of the study was to evaluate two physical activity recall instruments appropriate for use in epidemiologic studies of fifth grade children. The instruments were similar, except one (PACI) was administered in a personal interview, and the other (SAPAC) was self-completed in a group setting. Both forms required children to report the minutes during the previous day they spent in 21 common physical activities that represented a range of intensities, plus sedentary pursuits. To validate the recalls, children simultaneously wore an accelerometer (motion sensor) and a heart rate monitor for at least 8 h the day before the interview. Subjects were 55 boys and 70 girls from four regions of the United States. The Pearson correlation between the self- and interviewer-administered forms was 0.76 (P < 0.001). The interviewer-administered form correlated 0.51 (P < 0.001) with the heart rate index and 0.33 (P < 0.001) with the accelerometer score. The self-administered form correlated 0.57 (P < 0.001) with the heart rate index and 0.30, (P < 0.001) with the accelerometer score. It is concluded that both self-report forms received moderate support for their validity in all gender and ethnic subgroups. The self-administered format is more cost-effective. C1 TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA. LOUISIANA STATE UNIV,PENNINGTON BIOMED RES CTR,BATON ROUGE,LA 70808. NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT PEDIAT,LA JOLLA,CA 92093. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. RP Sallis, JF (reprint author), SAN DIEGO STATE UNIV,DEPT PSYCHOL,6363 ALVARADO COURT,SAN DIEGO,CA 92120, USA. RI Schmoelz, Camilie/D-1707-2012; Loureiro, Nuno/I-6400-2012 OI Schmoelz, Camilie/0000-0003-2221-9954; Loureiro, Nuno/0000-0002-1166-3219 FU NHLBI NIH HHS [UO1 HL 39852, UO1 HL 39870, UO1 HL 39927] NR 19 TC 206 Z9 211 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 1996 VL 28 IS 7 BP 840 EP 851 DI 10.1097/00005768-199607000-00011 PG 12 WC Sport Sciences SC Sport Sciences GA UZ387 UT WOS:A1996UZ38700011 PM 8832538 ER PT J AU Dame, JB Arnot, DE Bourke, PF Chakrabarti, D Christodoulou, Z Coppel, RL Cowman, AF Craig, AG Fischer, K Foster, J Goodman, N Hinterberg, K Holder, AA Holt, DC Kemp, DJ Lanzer, M Lim, A Newbold, CI Ravetch, JV Reddy, GR Rubio, J Schuster, SM Su, XZ Thompson, JK Vital, F Wellems, TE Werner, EB AF Dame, JB Arnot, DE Bourke, PF Chakrabarti, D Christodoulou, Z Coppel, RL Cowman, AF Craig, AG Fischer, K Foster, J Goodman, N Hinterberg, K Holder, AA Holt, DC Kemp, DJ Lanzer, M Lim, A Newbold, CI Ravetch, JV Reddy, GR Rubio, J Schuster, SM Su, XZ Thompson, JK Vital, F Wellems, TE Werner, EB TI Current status of the Plasmodium falciparum genome project SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Review DE genome project; malaria; mapping; expressed sequence tag; Plasmodium falciparum; review; yeast artificial chromosome; mung bean nuclease; cDNA; protozoa ID EXPRESSED SEQUENCE TAGS; YEAST ARTIFICIAL CHROMOSOMES; MUNG BEAN NUCLEASE; MULTIDRUG RESISTANCE GENE; RICH PROTEIN GENE; P-FALCIPARUM; CHLOROQUINE-RESISTANCE; CAENORHABDITIS-ELEGANS; ASPARTIC PROTEINASE; MALARIA PARASITES AB The Plasmodium falciparum Genome Project is a collaborative effort by many laboratories that will provide detailed molecular information about the parasite, which may be used for developing practical control measures. Initial goals are to prepare an electronically indexed clone bank containing partially sequenced clones representing up to 80% of the parasite's genes and to prepare an ordered set of overlapping clones spanning each of the parasite's 14 chromosomes. Currently, clones of genomic DNA, prepared as yeast artificial chromosomes, are arranged into contigs covering similar to 70% of the genome of parasite clone 3D7, gene sequence tags are available from more than contigs covering similar to 70% of the genome of parasite clone 3D7, gene sequence tags are available from more than 20% of the parasite's genes, and similar to 5% of the parasite's genes are tentatively identified from similarity searches of entries in the international sequence databases. A total of >0.5 Mb of P. falciparum sequence tag data is available. The gene sequence tags are presently being used to complete YAC contig assembly and localize the cloned genes to positions on the physical map in preparation for sequencing the genome. Routes of access to project information and services are described. C1 UNIV EDINBURGH,ICAPB,EDINBURGH EH9 3JN,MIDLOTHIAN,SCOTLAND. MENZIES SCH HLTH RES,CASUARINA,NT 0811,AUSTRALIA. UNIV CENT FLORIDA,ORLANDO,FL 32816. UNIV OXFORD,OXFORD OX3 9DU,ENGLAND. MONASH UNIV,CLAYTON,VIC 3168,AUSTRALIA. WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC 3050,AUSTRALIA. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02139. NATL INST MED RES,LONDON NW7 1AA,ENGLAND. UNIV WURZBURG,D-97070 WURZBURG,GERMANY. SLOAN KETTERING INST,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. RP Dame, JB (reprint author), UNIV FLORIDA,GAINESVILLE,FL 32611, USA. RI Coppel, Ross/A-6626-2008; Holt, Deborah/A-8002-2012; Holder, Anthony/A-7554-2013; Cowman, Alan/C-7642-2013; OI Coppel, Ross/0000-0002-4476-9124; Holder, Anthony/0000-0002-8490-6058; Cowman, Alan/0000-0001-5145-9004; Newbold, Chris/0000-0002-9274-3789; RUBIO, JUSTIN/0000-0003-3750-917X; Su, Xinzhuan/0000-0003-3246-3248 FU Medical Research Council [MC_U117532067]; Wellcome Trust NR 74 TC 47 Z9 47 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 1996 VL 79 IS 1 BP 1 EP 12 DI 10.1016/0166-6851(96)02641-2 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VA645 UT WOS:A1996VA64500001 PM 8844667 ER PT J AU Svaren, J Sevetson, BR Apel, ED Zimonjic, DB Popescu, NC Milbrandt, J AF Svaren, J Sevetson, BR Apel, ED Zimonjic, DB Popescu, NC Milbrandt, J TI NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; FINGER-ENCODING GENE; C-FOS; TRANSCRIPTIONAL ACTIVITY; CELLS; PROTEIN; EXPRESSION; DNA; SEQUENCES; RAT AB Previous work had identified a corepressor, NAB1, which represses transcriptional activation mediated by NGFI-A (also known as Egr-1, zif268, and Krox24) and Krox20. These zinc finger transcription factors are encoded by immediate-early genes and have been implicated in a wide variety of proliferative and differentiative processes. We have isolated and characterized another corepressor, NAB2, which is highly related to NAB1 within two discrete domains. The first conserved domain of NABZ mediates an interaction with the R1 domain of NGFI-A. NAB2 represses the activity of both NGFI-A and Krox20, and its expression is regulated by some of the same stimuli that induce NGFI-A expression, including serum stimulation of fibroblasts and nerve growth factor stimulation of PC12 cells. The human NABZ gene has been localized to chromosome 12q13.3-14.1, a region that is rearranged in several solid tumors, lipomas, uterine leiomyomata, and liposarcomas. Sequencing of the Caenorhabditis elegans genome has identified a gene that bears high homology to both NAB1 and NAB2, suggesting that NAB molecules fulfill an evolutionarily conserved role. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110. NCI,BIOL LAB,BETHESDA,MD 20892. OI Svaren, John/0000-0003-2963-7921 FU NCI NIH HHS [P01 CA49712]; NIDDK NIH HHS [T32-DK07296]; NIGMS NIH HHS [T32-GM07067] NR 58 TC 278 Z9 283 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3545 EP 3553 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600033 PM 8668170 ER PT J AU Broccoli, D Godley, IA Donehower, LA Varmus, HE deLange, T AF Broccoli, D Godley, IA Donehower, LA Varmus, HE deLange, T TI Telomerase activation in mouse mammary tumors: Lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSGENIC MICE; POLYMERASE-III; CHROMOSOME; DNA; REPEAT; YEAST; IDENTIFICATION; CARCINOGENESIS; SEQUENCE; WNT-1 AB Activation of telomerase in human cancers is thought to be necessary to overcome the progressive loss of telomeric DNA that accompanies proliferation of normal somatic cells. According to this model, telomerase provides a growth advantage to cells in,which extensive terminal sequence loss threatens viability. To test these ideas, we have examined telomere dynamics and telomerase activation during mammary tumorigenesis in mice carrying a mouse mammary tumor virus long terminal repeat-driven Wnt-1 transgene. We also analyzed Wnt-1-induced mammary tumors in mice lacking p53 function. Normal mammary glands, hyperplastic mammary glands, and mammary carcinomas all had the long telomeres (20 to 50 kb) typical of Mus musculus and did not show telomere shortening during tumor development. Nevertheless, telomerase activity and the RNA component of the enzyme were consistently upregulated in Wnt-1-induced mammary tumors compared with normal and hyperplastic tissues. The upregulation of telomerase activity and RNA also occurred during tumorigenesis in p53-deficient mice. The expression of telomerase RNA correlated strongly with histone H4 mRNA in all normal tissues grad tumors, indicating that the RNA component of telomerase is regulated,vith cell proliferation. Telomerase activity in the tumors was elevated to a greater extent than telomerase RNA, implying that the enzymatic activity of telomerase is regulated at additional levels. Our data suggest that the mechanism of telomerase activation in mouse mammary tumors is not linked to global loss of telomere function but involves multiple regulatory events including upregulation of telomerase RNA in proliferating cells. C1 ROCKEFELLER UNIV,CELL BIOL & GENET LAB,NEW YORK,NY 10021. NCI,DIV BASIC SCI,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RI de Lange, Titia de Lange/B-8263-2011 FU NIGMS NIH HHS [GM49046] NR 65 TC 154 Z9 159 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3765 EP 3772 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600056 PM 8668193 ER PT J AU Molkentin, JD Firulli, AB Black, BL Martin, JF Hustad, CM Copeland, N Jenkins, N Lyons, G Olson, EN AF Molkentin, JD Firulli, AB Black, BL Martin, JF Hustad, CM Copeland, N Jenkins, N Lyons, G Olson, EN TI MEF2B is a potent transactivator expressed in early myogenic lineages SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING-FACTOR; TRANSCRIPTION FACTORS; SKELETAL-MUSCLE; MOUSE EMBRYO; GENE; ELEMENTS; IDENTIFICATION; PROTEINS; HEART; CELLS AB There are four members of the myocyte enhancer binding factor 2 (MEF2) family of transcription factors, MEF2A, -B, -C, and -D, that have homology within an amino-terminal MADS box and an adjacent MEF2 domain that together mediate dimerization and DNA binding. MEF2A, -C, and -D have previously been shown to bind an A/T-rich DNA sequence in the control regions of numerous muscle-specific genes, whereas MEF2B was reported to be unable to bind this sequence unless the carboxyl terminus was deleted. To further define the functions of MEF2B, we analyzed its DNA binding and transcriptional activities. In contrast to previous studies, our results show that MEF2B binds the same DNA sequence as other members of the MEF2 family and acts as a strong transactivator through that sequence. Transcriptional activation by MEF2B is dependent on the carboxyl terminus, which contains two conserved sequence motifs found in all vertebrate MEF2 factors. During mouse embryogenesis, MEF2B transcripts are expressed in the developing cardiac and skeletal muscle lineages in a temporospatial pattern distinct from but overlapping with those of the other Mef2 genes. The mouse Mef2b gene maps to chromosome 8 and is unlinked to other Mef2 genes; its intron-exon organization is similar to that of the other vertebrate Mef2 genes and the single Drosophila Mef2 gene, consistent with the notion that these different Mef2 genes evolved from a common ancestral gene. C1 UNIV TEXAS,SW MED CTR,HUMAN CTR BASIC CANC RES,DALLAS,TX 75235. UNIV WISCONSIN,SCH MED,DEPT ANAT,MADISON,WI 53706. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77039. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 51 TC 83 Z9 86 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3814 EP 3824 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600062 PM 8668199 ER PT J AU Duncan, R Collins, I Tomonaga, T Zheng, T Levens, D AF Duncan, R Collins, I Tomonaga, T Zheng, T Levens, D TI Unique transactivation sequence motif is found in the carboxyl-terminal domain of the single-strand-binding protein FBP (vol 16, pg 2274, 1996) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition RP Duncan, R (reprint author), NCI,PATHOL LAB,BLDG 10,BETHESDA,MD 20892, USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3980 EP 3980 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600079 ER PT J AU Zu, K Sikes, ML Haynes, SR Beyer, AL AF Zu, K Sikes, ML Haynes, SR Beyer, AL TI Altered levels of the Drosophila HRB87F/hrp36 hnRNP protein have limited effects on alternative splicing in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PRE-MESSENGER-RNA; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN-A1; DOPA-DECARBOXYLASE GENE; AMPHIBIAN GERMINAL VESICLE; CONSERVED FAMILY; SITE SELECTION; HEAT-SHOCK; NASCENT TRANSCRIPTS; PACKAGING PROTEINS; COMPLEX PROTEIN-A1 AB The Drosophila melanogaster genes Hrb87F and Hrb98DE encode the fly proteins HRB87F and HRB98DE (also known as hrp36 and hrp38, respectively), that are most similar in sequence and function to mammalian A/B-type hnRNP proteins. Using overexpression and deletion mutants of Hrb87F, we have tested the hypothesis that the ratio of A/B hnRNP proteins to SR family proteins modulates certain types of alternative splice-site selection. In flies in which HRB87F/hrp36 had been overexpressed 10- to 15-fold above normal levels, aberrant internal exon skipping was induced in at least one endogenous transcript, the dopa decarboxylase (Ddc) pre-mRNA, which previously had been shown to be similarly affected by excess HRB98DE/hrp38. In a second endogenous pre-mRNA, excess HRB87F/hrp36 had no effect on alternative 3' splice-site selection, as expected from mammalian hnRNP studies. Immunolocalization of the excess hnRNP protein showed that it localized correctly to the nucleus, specifically to sites on or near chromosomes, and that the peak of exon-skipping activity in Ddc RNA correlated with the peak of chromosomally associated hnRNP protein. The chromosomal association and level of the SR family of proteins were not significantly affected by the large increase in hnRNP proteins during this time period. Although these results are consistent with a possible role for hnRNP proteins in alternative splicing, the more interesting finding was the failure to detect significant adverse effects on flies with a greatly distorted ratio of hnRNPs to SR proteins. Electron microscopic visualization of the general population of active genes in flies overexpressing hnRNP proteins also indicated that the great majority of genes seemed normal in terms of cotranscriptional RNA processing events, although there were a few abnormalities consistent with rare exon-skipping events. Furthermore, in a Hrb87F null mutant, which is viable, the normal pattern of Ddc alternative splicing was observed, indicating that HRB87F/hrp36 is not required for Ddc splicing regulation. Thus, although splice-site selection can be affected in at least a few genes by gross overexpression of this hnRNP protein, the combined evidence suggests that if it plays a general role in alternative splicing in vivo, the role can be provided by other proteins with redundant functions, and the role is independent of its concentration relative to SR proteins. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-39271] NR 79 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 1996 VL 7 IS 7 BP 1059 EP 1073 PG 15 WC Cell Biology SC Cell Biology GA UX918 UT WOS:A1996UX91800005 PM 8862520 ER PT J AU Hayashi, N Hasegawa, K Komine, A Tanaka, Y McLachlan, JA Barrett, JC Tsutsui, T AF Hayashi, N Hasegawa, K Komine, A Tanaka, Y McLachlan, JA Barrett, JC Tsutsui, T TI Estrogen-induced cell transformation and DNA adduct formation in cultured syrian hamster embryo cells SO MOLECULAR CARCINOGENESIS LA English DT Article ID SISTER CHROMATID EXCHANGE; EXOGENOUS METABOLIC-ACTIVATION; NEOPLASTIC TRANSFORMATION; ANEUPLOIDY INDUCTION; COVALENT BINDING; CHROMOSOMAL-ABERRATIONS; POSSIBLE MECHANISM; MAMMALIAN-CELLS; PROTEIN INVITRO; DIETHYLSTILBESTROL AB To study the possible involvement of DNA damage in cell transformation induced by estrogens, we examined whether DNA adduct formation is elicited in cultured Syrian hamster embryo (SHE) cells treated with estrogens and their derivatives by means of the P-32-postlabeling assay. Morphological transformation of the cells was induced by treatment with diethylstilbestrol (DES) at 1-10 mu g/mL for 24 h but not by treatment with its derivatives trans, trans-dienestrol (alpha-DIES) or cis, cis-dienestrol (beta-DIES) at 1-10 mu g/mL for 24 h. Similarly, DNA adduct formation was elicited by exposure of SHE cells to DES at 1-10 mu g/mL for 24 h but not by either alpha-DIES or beta-DIES. Treatment of SHE cells with DES at 1-10 mu g/mL for 2 h in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant enhanced morphological transformation in a dose-dependent manner. Our previous studies have demonstrated that exposure of SHE cells to DES under the same conditions with exogenous metabolic activation induces somatic mutations at the Na+/K+ ATPase locus. Therefore, we examined whether with exogenous metabolic activation DES induced DNA adduct formation in SHE cells. DNA adducts were not detected when SHE cells were treated with DES at 1-10 mu g/mL for 2 h in the presence of exogenous metabolic activation. Treatment with 17 beta-estradiol (E(2)), 2-hydroxyestradiol (2-OH E(2)), or 4-hydroxyestradiol (4-OH E(2)) at 1 mu g/mL for 24 h induced DNA adduct formation in the cells, in parallel with the induction of cell transformation. The rank order of DNA adduct formation was 4-OH E(2) > 2-OH E(2) > E(2). The results indicate that estrogens induce DNA adduct formation in cultured SHE cells, but the induction may not be the only mechanism relevant to the initiation of cell transformation. (C) 1996 Wiley-Liss, Inc. C1 NIPPON DENT UNIV TOKYO,SCH DENT,DEPT PHARMACOL,CHIYODA KU,TOKYO 102,JAPAN. NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC. NIEHS,MOL CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC. NR 59 TC 40 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 1996 VL 16 IS 3 BP 149 EP 156 DI 10.1002/(SICI)1098-2744(199607)16:3<149::AID-MC5>3.0.CO;2-C PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VA225 UT WOS:A1996VA22500005 PM 8688150 ER PT J AU Ohe, K Ikuyama, S Takayanagi, R Kohn, LD Nawata, H AF Ohe, K Ikuyama, S Takayanagi, R Kohn, LD Nawata, H TI Interferon-gamma suppresses thyrotropin receptor promoter activity by reducing thyroid transcription factor-1 (TTF-1) binding to its recognition site SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CULTURED HUMAN THYROCYTES; TISSUE-SPECIFIC EXPRESSION; GENE-EXPRESSION; THYROGLOBULIN PROMOTER; RESPONSE ELEMENT; EPITHELIAL-CELLS; INHIBITION; PROTEIN; MECHANISMS; ANTIGEN AB Interferon-gamma (IFN gamma) is known to suppress the expression of thyroid-specific genes, such as thyroglobulin, thyroid peroxidase, and the TSH receptor (TSHR). In the present study, we show that this reflects, in part, a transcriptional action mediated by thyroid transcription factor-1 (TTF-1), Thus, transfected into rat FRTL-5 cells, the activity of reporter plasmids, containing rat TSHR promoter ligated to a chloramphenicol acetyltransferase gene, was significantly suppressed in the presence of rat IFN gamma. A -199-bp promoter construct showed the greatest suppression by IFN gamma whereas a -177-bp construct, in which the TTF-1 binding site was deleted, showed less suppressibility. The suppressive effect was rat IFN gamma-specific, since human IFN alpha, -beta, and -gamma exhibited no significant effects, The effect was concentration-dependent from 3-50 U/ml. in FRT rat thyroid cells that do not express TTF-1, IFN gamma-induced suppression on the promoter activity was not observed, In addition, when the TTF-1 binding site was mutated so that TTF-1 can not bind, IFN gamma-induced suppression was significantly reduced, In gel mobility shift analyses, a protein-DNA complex formed by TTF-l was reduced when the nuclear extract prepared from IFN gamma-treated FRTL-5 cells was used; however, expression of TTF-l mRNA and TTF-1 protein, which were assessed by Northern blot analysis and Western blot analysis, respectively, were not affected by IFN gamma treatment of FRTL-5 cells, Instead, reduction of DNA-binding affinity of TTF-1 was evident when competition analysis was performed in gel mobility shift analysis; From these results, we conclude that IFN gamma suppresses TSHR promoter activity, in part, by reducing TTF-l binding to its recognition site. We also raise the possibility that the suppressive effect of IFN gamma on promoter activity is mediated by additional element(s) and factor(s) downstream of the TTF-l site. C1 KYUSHU UNIV, FAC MED, DEPT INTERNAL MED 3, HIGASHI KU, FUKUOKA 81282, JAPAN. NIDDKD, CELL REGULAT SECT, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NR 51 TC 20 Z9 20 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1996 VL 10 IS 7 BP 826 EP 836 DI 10.1210/me.10.7.826 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV734 UT WOS:A1996UV73400005 PM 8813723 ER PT J AU Baker, J Hardy, MP Zhou, J Bondy, C Lupu, F Bellve, AR Efstratiadis, A AF Baker, J Hardy, MP Zhou, J Bondy, C Lupu, F Bellve, AR Efstratiadis, A TI Effects of an Igf1 gene null mutation on mouse reproduction SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID GROWTH FACTOR-I; FOLLICLE-STIMULATING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; MESSENGER-RIBONUCLEIC-ACID; RAT GRANULOSA-CELLS; FETAL LEYDIG-CELLS; RECEPTOR GENE; POSTNATAL-DEVELOPMENT; SERUM CONCENTRATIONS; LUTEINIZING-HORMONE AB Both sexes of adult mice homozygous for a targeted mutation of the Igf1 gene, encoding insulinlike growth factor I, are infertile dwarfs (similar to 30% of normal size). The testes are reduced in size less than expected from the degree of dwarfism but sustain spermatogenesis only at 18% of the normal level, The epididymides are overall nearly allometric to the reduced body weight, but the distal regions of the duct, vas deferens, seminal vesicles, and prostate are vestigial. Despite the mutational impact on the epididymis, capacitated sperm are able to fertilize wild type eggs in vitro, It is hypothesized that the infertility of male mutants is caused by failure of androgenization resulting in absence of mating behavior, due to drastically reduced levels of serum testosterone (18% of normal), This hormonal deficiency was correlated with an ultrastructural analysis of mutant Leydig cells revealing a significant developmental delay, while assays in organ culture showed that the basal and LH-stimulated production of testosterone by testicular parenchyma is reduced in comparison with wild type controls, The female mutants fail to ovulate even after administration of gonadotropins, which is apparently the primary cause of their infertility, and possess an infantile uterus that exhibits a dramatic hypoplasia especially in the myometrium. The phenotypic manifestations of the mutation were correlated with the localization of transcripts for insulin-like growth factor I and its cognate receptor in wild type reproductive tissues by in situ hybridization. C1 COLUMBIA UNIV, DEPT GENET & DEV, NEW YORK, NY 10032 USA. COLUMBIA UNIV, DEPT ANAT & CELL BIOL, NEW YORK, NY 10032 USA. COLUMBIA UNIV, DEPT UROL, NEW YORK, NY 10032 USA. COLUMBIA UNIV, CTR REPROD SCI, NEW YORK, NY 10032 USA. POPULAT COUNCIL, CTR BIOMED RES, NEW YORK, NY 10021 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-28342, HD-29010, HD-32588] NR 108 TC 413 Z9 423 U1 1 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1996 VL 10 IS 7 BP 903 EP 918 DI 10.1210/me.10.7.903 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV734 UT WOS:A1996UV73400012 PM 8813730 ER PT J AU Peters, JM Zhou, YC Ram, PA Lee, SST Gonzalez, FJ Waxman, DJ AF Peters, JM Zhou, YC Ram, PA Lee, SST Gonzalez, FJ Waxman, DJ TI Peroxisome proliferator-activated receptor alpha required for gene induction by dehydroepiandrosterone-3 beta-sulfate SO MOLECULAR PHARMACOLOGY LA English DT Article ID FATTY-ACIDS; CLOFIBRIC ACID; RAT-LIVER; EXPRESSION; CYTOCHROME-P450; STEROIDS; ENZYMES; HORMONE; CANCER; MEMBER AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) mediates the effects of foreign chemical peroxisome proliferators on liver and kidney, including the induction of peroxisomal, mitochondrial, and microsomal enzymes involved in beta-oxidation of fatty acids. However, the role of this receptor in the peroxisome proliferative effects of the endogenous steroid dehydroepiandrosterone (DHEA) is not known. DHEA-3 beta-sulfate (DHEA-S) is shown to induce a liver peroxisome proliferative response in rats in vivo at a dose at which DHEA is much less active, which is consistent with cultured hepatocyte studies indicating a requirement for sulfation for the activation of DHEA. Transient transfection experiments demonstrated that in contrast to the prototypic foreign chemical peroxisome proliferator pirinixic acid, DHEA-S and its 17 beta-reduced metabolite, 5-androstene-3 beta, 17 beta-diol-3 beta-sulfate, are inactive in mediating trans-activation by PPAR alpha in COS-1 cells. Two other mammalian PPAR isoforms, gamma and delta/Nuc1, were also inactive with respect to DHEA-S trans-activation. To test whether PPAR alpha mediates peroxisomal gene induction by DHEA-S in intact animals, we administered DHEA-S or clofibrate to mice lacking a functional PPAR alpha gene. Both peroxisome proliferators markedly increased hepatic expression of two microsomal cytochrome P450 4A proteins as well as six mRNAs known to be associated with the peroxisomal proliferative response in wild-type mice. In contrast, neither DHEA-S nor clofibrate induced these hepatic proteins and mRNAs in PPAR alpha-deficient mice. Clofibrate-induced expression of kidney CYP4A mRNAs was also blocked in the PPAR alpha gene knockout mice. Thus, despite its unresponsiveness to steroidal peroxisome proliferators in transfection assays, PPAR alpha is obligatory for DHEA-S-stimulated hepatic peroxisomal gene induction. DHEA-S, or one of its metabolites, may thus serve as an important endogenous regulator of liver peroxisomal enzyme expression via a PPAR alpha-mediated pathway. C1 BOSTON UNIV,DEPT BIOL,DIV CELL & MOLEC BIOL,BOSTON,MA 02215. NCI,MOLEC CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Peters, Jeffrey/D-8847-2011 FU NIEHS NIH HHS [ES07381] NR 47 TC 118 Z9 119 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1996 VL 50 IS 1 BP 67 EP 74 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UY027 UT WOS:A1996UY02700010 PM 8700121 ER PT J AU Rovati, GE Shrager, R Nicosia, S Munson, PJ AF Rovati, GE Shrager, R Nicosia, S Munson, PJ TI KINFIT II: A nonlinear least-squares program for analysis of kinetic binding data SO MOLECULAR PHARMACOLOGY LA English DT Article AB We describe a versatile computer program for least-squares fitting of ligand/receptor association and dissociation curves from several experiments simultaneously. The program is designed to handle any number of classes of binding sites reacting with a single ligand that may have two forms: labeled and unlabeled. For a single class of binding sites, the exact, analytical solution is used to generate the computed curves. For more than one class of sites, the computed curves are generated through numerical solution of a set of ordinary differential equations. The parameters determined with this procedure are the on- and off-rate constants and the concentrations of each binding site class. An extensive selection of experimental designs can be processed. The times of observation may be freely chosen, although that choice will affect the quality of the results. Starting with a sample material (e.g., cells, membranes, macromolecules), one can preincubate (to equilibrium) with any combination of labeled and unlabeled ligand. One can then perturb the system by adding any combination of labeled and cold ligand or simply diluting the sample; such an experiment can be continued through several perturbations. A variety of such runs may be combined for analysis as a single data set. C1 NIH,LAB APPL STUDIES,BETHESDA,MD 20892. NIH,ANALYT BIOSTAT SECT,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Rovati, GE (reprint author), UNIV MILAN,INST PHARMACOL SCI,MOLEC PHARMACOL LAB,VIA BALZARETTI 9,I-20133 MILAN,ITALY. OI Rovati, G.Enrico/0000-0002-8788-9783 NR 15 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1996 VL 50 IS 1 BP 86 EP 95 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UY027 UT WOS:A1996UY02700013 PM 8700124 ER PT J AU Tew, KD Monks, A Barone, L Rosser, D Akerman, G Montali, JA Wheatley, JB Schmidt, DE AF Tew, KD Monks, A Barone, L Rosser, D Akerman, G Montali, JA Wheatley, JB Schmidt, DE TI Glutathione-associated enzymes in the human cell lines of the national cancer institute drug screening program SO MOLECULAR PHARMACOLOGY LA English DT Article ID S-TRANSFERASE-PI; PLACENTAL FORM; SUBUNIT CDNA; HUMAN COLON; EXPRESSION; TUMOR; CYTOTOXICITY; RESISTANCE; SEQUENCES; CARCINOMA AB The steady state expression of glutathione S-transferases (GSTs) at both the protein and mRNA level is reported for the 60 tumor cell lines that are used for the National Cancer Institute Drug Screening Program. Individual GST isozymes were separated, identified, and quantified (with reverse-phase calibration curves) through a novel high performance liquid chromatographic procedure. GSTP1 was the predominant isozyme and was found at quantifiable levels in all but two of the cell lines. This isozyme ranged from 0.03% to 2.7% of the total cytosolic protein. For the mu family, 90% of the lines had GSTM2, 68% had GSTM3, but only 28% were positive for the M1 phenotype. The M1 proportion is lower than would be expected from the standard M1 null phenotype for human populations. Isozymes of the a:family were detected only at very low levels in 35% of the lines. Significant quantitative correlations among enzyme activity, total enzyme protein, and mRNA were shown for GSTP1. However, such relationships were not apparent for the mu or alpha families. Levels of glutathione (GSH), and the transcript levels of other enzymes involved in GSH homeostasis were determined. gamma-Glutamyl cysteine synthetase (gamma-GCS) was present in ail cell lines, but did not correlate with levels of intracellular GSH. Glyoxalase-1 and gamma-glutamyl transpeptidase, both involved in GSH salvage, were found in 100% and 70% of the cell lines, respectively. Using a pattern-matching computer program, COMPARE, we compared and correlated the arrays of mRNA and protein levels with the pattern of chemosensitivity or chemoresistance of the 60 cell lines with 175 agents constituting a standard agent database. This database is composed of compounds to which a putative mechanism of action has been assigned. Although Pearson correlation coefficients relating the target and drug patterns were generally modest, when the patterns for the enzyme protein and mRNA levels for GST pi were correlated to drug sensitivity patterns, the list of 30 agents most closely matching (for which p < 0.05) was enriched with alkylating agents, gamma-GCS also showed an enrichment of alkylating agents in the COMPARE correlations, indicating that high levels of gamma-GCS may be an important determinant of resistance. In contrast, none of the other enzymes or GSH had patterns of expression that resulted in an obvious correlation to the sensitivity or resistance of alkylating agents. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. TERRAPIN TECHNOL INC,S SAN FRANCISCO,CA 94080. RP Tew, KD (reprint author), FOX CHASE CANC CTR,DEPT PHARMACOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. NR 62 TC 138 Z9 141 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1996 VL 50 IS 1 BP 149 EP 159 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UY027 UT WOS:A1996UY02700020 PM 8700107 ER PT J AU Ahluwalia, GS Gag, WY Mitsuya, H Johns, DG AF Ahluwalia, GS Gag, WY Mitsuya, H Johns, DG TI 2',3'-didehydro-3'-deoxythymidine: Regulation of its metabolic activation by modulators of thymidine-5'-triphosphate biosynthesis SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN THYMIDINE KINASE-1; 3'-DEOXYTHYMIDIN-2'-ENE D4T; REVERSE-TRANSCRIPTASE; CELLULAR PHARMACOLOGY; INVITRO; INHIBITION; POTENT; REPLICATION; CELLS AB The anti-human immunodeficiency virus (anti-HN) agent 2',3'-didehydro3'-deoxythymidine (D4T), like other 2',3'-dideoxynucleosides, requires conversion to its 5'-triphosphate to exert its pharmacological effect. Although D4T-triphosphate is unusually potent as an inhibitor of HIV-1 reverse transcriptase, the phosphorylation of the drug at low dose levels is inefficient because of its low affinity as an alternate substrate for the initial phosphorylation enzyme thymidine kinase. Because thymidine kinase is under feedback regulatory control by the physiological deoxynucleoside-5'-triphosphate dTTP, we examined the effect on D4T phosphorylation and thus, potentially, on its antiviral activity, of a variety of agents that lower intracellular dTTP pools. We found that agents that inhibit the de novo pyrimidine biosynthetic pathway have the ability to increase D4T phosphorylation, the most effective being two inhibitors of thymidylate formation, methotrexate and 5-fluoro-2'-deoxyuridine, compounds that block the enzymes dihydrofolate reductase and thymidylate synthetase, respectively. Because HIV itself tacks the capacity to synthesize dTTP acid the other deoxynucleoside triphosphates essential for viral replication, combinations of D4T with modulatory agents that deplete host-cell dTTP, unlike conventional anti-HIV drug monotherapy directed solely at viral enzymes, have the ability to inhibit replication of mutant HIV strains as well as of wild-type virus. C1 NCI,NIH,MED CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,NIH,EXPTL RETROVIROL SECT,MED BRANCH,CLIN SCI DIV,BETHESDA,MD 20892. NR 34 TC 33 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1996 VL 50 IS 1 BP 160 EP 165 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UY027 UT WOS:A1996UY02700021 PM 8700108 ER PT J AU Licinio, J AF Licinio, J TI The tension between reductionist and integrative approaches in molecular psychiatry SO MOLECULAR PSYCHIATRY LA English DT Editorial Material RP Licinio, J (reprint author), NIMH,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 12 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 JUL PY 1996 VL 1 IS 3 BP 165 EP 167 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG816 UT WOS:A1996VG81600001 PM 9118333 ER PT J AU Leshner, AI AF Leshner, AI TI Drug abuse and addiction research: Implications for the field of psychiatry SO MOLECULAR PSYCHIATRY LA English DT Editorial Material RP Leshner, AI (reprint author), NATL INST DRUG ABUSE,5600 FISHERS LANE,ROOM 10-05,ROCKVILLE,MD, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 1996 VL 1 IS 3 BP 168 EP 169 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG816 UT WOS:A1996VG81600002 PM 9118334 ER PT J AU Vitkovic, L AF Vitkovic, L TI Are viruses involved in mental disorders? SO MOLECULAR PSYCHIATRY LA English DT Article C1 NIMH,DIV NEUROSCI & BEHAV SCI,NIH,ROCKVILLE,MD 20857. NR 6 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 1996 VL 1 IS 3 BP 170 EP 171 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG816 UT WOS:A1996VG81600003 PM 9118335 ER PT J AU Hu, RJ AF Hu, RJ TI New research on psychiatric genetics at the 149th Annual Meeting of the American Psychiatric Association SO MOLECULAR PSYCHIATRY LA English DT Article RP Hu, RJ (reprint author), NIDDK,NEUROSCI LAB,NIH,BLDG 8,ROOM 105,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 1996 VL 1 IS 3 BP 174 EP 175 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VG816 UT WOS:A1996VG81600005 PM 9118337 ER PT J AU Zeiger, E AF Zeiger, E TI The MINISCREEN assay SO MUTAGENESIS LA English DT Letter RP Zeiger, E (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JUL PY 1996 VL 11 IS 4 BP 415 EP 415 DI 10.1093/mutage/11.4.415 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA UX266 UT WOS:A1996UX26600014 PM 8671767 ER PT J AU Peters, R Sikorski, RS AF Peters, R Sikorski, RS TI Centrifugation on the Web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138, 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 JUL PY 1996 VL 14 IS 7 BP 899 EP 899 DI 10.1038/nbt0796-899a PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UV620 UT WOS:A1996UV62000046 ER PT J AU Hieter, P Bassett, DE Valle, D AF Hieter, P Bassett, DE Valle, D TI The yeast genome - A common currency SO NATURE GENETICS LA English DT Editorial Material C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Hieter, P (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,725 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 16 TC 26 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1996 VL 13 IS 3 BP 253 EP 255 DI 10.1038/ng0796-253 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UU283 UT WOS:A1996UU28300002 PM 8673115 ER PT J AU WynshawBoris, A AF WynshawBoris, A TI Model mice and human disease SO NATURE GENETICS LA English DT Editorial Material RP WynshawBoris, A (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 5 TC 32 Z9 33 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1996 VL 13 IS 3 BP 259 EP 260 DI 10.1038/ng0796-259 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UU283 UT WOS:A1996UU28300006 PM 8673118 ER PT J AU Koonin, EV Altschul, SF Bork, P AF Koonin, EV Altschul, SF Bork, P TI Functional motifs SO NATURE GENETICS LA English DT Letter ID ALIGNMENT C1 MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. EUROPEAN MOLEC BIOL LAB,D-690012 HEIDELBERG,GERMANY. RP Koonin, EV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 27 TC 312 Z9 315 U1 0 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1996 VL 13 IS 3 BP 266 EP 268 DI 10.1038/ng0796-266 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UU283 UT WOS:A1996UU28300009 PM 8673121 ER PT J AU Hirschhorn, R Yang, DRX Puck, JM Huie, ML Jiang, CK Kurlandsky, LE AF Hirschhorn, R Yang, DRX Puck, JM Huie, ML Jiang, CK Kurlandsky, LE TI Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency SO NATURE GENETICS LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN-LYMPHOCYTES; ADA; IDENTIFICATION; MISSENSE; DNA; DEOXYADENOSINE; CHILDREN AB Somatic mosaicism in genetic disease generally results from a de novo deleterious mutation during embryogenesis. We now describe a somatic mosaicism due to the unusual mechanism of in vivo reversion to normal of an inherited mutation. The propositus was an adenosine deaminase-deficient (ADA(-)) child with progressive clinical improvement and unexpectedly mild biochemical and immunologic abnormalities. Mosaicism due to reversion was evidenced by absence of a maternally transmitted deleterious mutation in 13/15 authenticated B cell lines and in 17% of single alleles cloned from blood DNA, despite retention of a maternal 'private' ADA polymorphism linked to the mutation. Establishment of significant somatic mosaicism following reversion to normal could modify any disorder in which revertant cells have a selective advantage. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MICHIGAN STATE UNIV,COLL HUMAN MED,DEPT PEDIAT & HUMAN DEV,GRAND RAPIDS,MI 49546. RP Hirschhorn, R (reprint author), NYU,SCH MED,DEPT MED,DIV MED GENET,550 1ST AVE,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [AI R37 10343] NR 28 TC 156 Z9 159 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1996 VL 13 IS 3 BP 290 EP 295 DI 10.1038/ng0796-290 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA UU283 UT WOS:A1996UU28300016 PM 8673127 ER PT J AU Boyer, PL Hughes, SH AF Boyer, PL Hughes, SH TI Nucleoside-analogue resistance involves the p66 subunit of HIV-1 RT SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; HETERODIMER; DNA; MUTAGENESIS RP Boyer, PL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUL PY 1996 VL 3 IS 7 BP 579 EP 580 DI 10.1038/nsb0796-579 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UV280 UT WOS:A1996UV28000006 PM 8673598 ER PT J AU Giorgi, O Carboni, G Frau, V Orlandi, M Valentini, V Feldman, A Corda, MG AF Giorgi, O Carboni, G Frau, V Orlandi, M Valentini, V Feldman, A Corda, MG TI Anticonvulsant effect of felbamate in the pentylenetetrazole kindling model of epilepsy in the rat SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE felbamate; pentylenetetrazol (PTZ); kindling; convulsions; dizocilpine; NMDA receptors; GABA(A) receptors; picrotoxin; isoniazid ID METHYL-D-ASPARTATE; GAMMA-AMINOBUTYRIC-ACID; INSENSITIVE GLYCINE RECEPTORS; MK-801 PREVENTS; GABA; BRAIN; DECREASE; SEIZURES; ANTAGONISM; INHIBITORS AB The present study was designed to examine the ability of felbamate, a novel antiepileptic agent, to antagonize the increase in seizure severity (i.e., chemical kindling) produced by chronic treatment with initially subconvulsant doses of pentylenetetrazol (PTZ). Rats were treated with PTZ (30 mg/kg, ii?, three times a week) for 8 consecutive weeks. Two other groups of rats received felbamate (300 or 400 mg/kg, i.p.), 90 min before each dose of PTZ. Pretreatment with felbamate at either dose prevented the progression of rank of seizures during chronic treatment with PTZ. Thus, the mean seizure score by the end of the chronic treatment (0-5 scale) was 0 in vehicle treated controls, 3.3 in rats treated with PTZ alone, 1.5 in rats treated with PTZ plus felbamate (300 mg/kg, i.p.) and 0.9 in the group treated with PTZ plus felbamate (400 mg/kg, i.p.). Felbamate also antagonized the long-term increase in the sensitivity to the convulsant effects of GABA function inhibitors observed in PTZ-kindled rats. Thus, the administration of a challenge dose of isoniazid (120 mg/kg, s.c.), picrotoxin (1.5 mg/kg, i.p.) or PTZ itself (15 mg/kg, i.p.), 15 to 45 days after the end of the chronic treatment regimen, induced convulsions in > 80% of PTZ-kindled rats and in < 20% of rats treated with PTZ + felbamate(400 mg/kg). The results are discussed in terms of the multiple mechanisms that can contribute to the anticonvulsant action of felbamate in the PTZ kindling model of epilepsy. C1 NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. RP Giorgi, O (reprint author), UNIV CAGLIARI,DEPT TOXICOL,VIALE A DIAZ 182,I-09126 CAGLIARI,ITALY. NR 31 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JUL PY 1996 VL 354 IS 2 BP 173 EP 178 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA458 UT WOS:A1996VA45800011 PM 8857594 ER PT J AU Hirashima, N Etcheberrigaray, R Bergamaschi, S Racchi, M Battaini, F Binetti, G Govoni, S Alkon, DL AF Hirashima, N Etcheberrigaray, R Bergamaschi, S Racchi, M Battaini, F Binetti, G Govoni, S Alkon, DL TI Calcium responses in human fibroblasts: A diagnostic molecular profile for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; calcium; bradykinin; TEA; bombesin; fibroblast ID CYTOSOLIC FREE-CALCIUM; GTP-BINDING PROTEIN; BRADYKININ RECEPTORS; INTRACELLULAR CALCIUM; INOSITOL PHOSPHATES; POTASSIUM CHANNEL; SKIN FIBROBLASTS; MEMORY STORAGE; LYMPHOCYTES; DONORS AB We have previously identified alterations of K+ channel function, IP3-mediated calcium release, and Cp20 (a memory-associated GTP binding protein) in fibroblasts from AD patients vs. controls. In the present study we introduce a scoring system based on these response alterations that integrates two or more alterations (and their degree) in AD vs. control fibroblasts. This scoring system generates an index that distinguishes AD patients from controls with both high specificity and sensitivity. We also show that low doses of bradykinin elicit intracellular calcium release almost exclusively in AD cell lines in an all or none fashion that provide a clear measurement of enhanced IP3-mediated function in AD vs. controls. C1 NINCDS,LAB ADAPT SYST,NIH,BETHESDA,MD 20892. UNIV MILAN,IST PHARMACOL SCI,MILAN,ITALY. SACRED HEART FBF HOSP BRESCIA,ALZHEIMERS DEPT,BRESCIA,ITALY. UNIV PAVIA,INST PHARMACOL,PAVIA,ITALY. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015; Binetti, Giuliano/K-4519-2016; OI Govoni, Stefano/0000-0002-7243-6837; Binetti, Giuliano/0000-0003-2759-5844; Racchi, Marco/0000-0002-7185-7808 NR 41 TC 46 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1996 VL 17 IS 4 BP 549 EP 555 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UZ206 UT WOS:A1996UZ20600008 PM 8832629 ER PT J AU Shibutani, M Kim, E Lazarovici, P Oshima, M Guroff, G AF Shibutani, M Kim, E Lazarovici, P Oshima, M Guroff, G TI Preparation of a cell-free translation system from PC12 cells SO NEUROCHEMICAL RESEARCH LA English DT Article DE PC12; translation; S10; epidermal growth factor receptor; luciferase ID NERVE GROWTH-FACTOR; MESSENGER-RNA; FIREFLY LUCIFERASE; PROTEIN-SYNTHESIS; FACTOR RECEPTOR; INVITRO; INITIATION; LINE; PHOSPHORYLATION; POLIOVIRUS AB The postmitochondrial fraction (S10) contains the cellular components essential for translation, and a high-sail wash (HSW) of the ribosomes is enriched in eukaryotic initiation factors. This report describes the preparation of a cell-free translation system utilizing an S10 extract from PC12 cells. The products synthesized from either firefly luciferase mRNA or PC12 cell poly(A) RNAs in the PC12-S10 extract were increased by the addition of the HSW from PC12 cells. Increases in the translation of luciferase mRNA by the addition of PC12-HSW were dose-dependent and also dependent on the time of incubation. The translation of human epidermal growth factor receptor (hEGFR) mRNA could also be detected in the PC12-S10 extract translation system by immunoprecipitation. N-linked glycosylation of the translation products also was observed. The efficiency of translation was altered by the addition of Mg2+ or K+, and optimization of the concentrations of these ions was necessary for each mRNA. The translation system made from PC12 cells, then, is capable of the synthesis of proteins of relatively high molecular weight and should be useful for analyzing mechanisms of translational control during proliferation and differentiation of cells from a neuronal lineage. C1 NICHHD,GROWTH FACTORS SECT,NIH,BETHESDA,MD 20892. RI Shibutani, Makoto/C-2510-2013 NR 30 TC 4 Z9 4 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUL PY 1996 VL 21 IS 7 BP 801 EP 807 DI 10.1007/BF02532303 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VE308 UT WOS:A1996VE30800010 PM 8873084 ER PT J AU Litvan, I Agid, Y Calne, D Campbell, G Dubois, B Duvoisin, RC Goetz, CG Golbe, LI Grafman, J Growdon, JH Hallett, M Jankovic, J Quinn, NP Tolosa, E Zee, DS Chase, TN FitzGibbon, EJ Hall, Z Juncos, J Nelson, KB Oliver, E Pramstaller, P Reich, SG Verny, M AF Litvan, I Agid, Y Calne, D Campbell, G Dubois, B Duvoisin, RC Goetz, CG Golbe, LI Grafman, J Growdon, JH Hallett, M Jankovic, J Quinn, NP Tolosa, E Zee, DS Chase, TN FitzGibbon, EJ Hall, Z Juncos, J Nelson, KB Oliver, E Pramstaller, P Reich, SG Verny, M TI Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): Report of the NINDS-SPSP International Workshop SO NEUROLOGY LA English DT Editorial Material ID POSITRON EMISSION TOMOGRAPHY; MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; SUBCORTICAL DEMENTIA; PURE AKINESIA; GAZE PALSY; HYPOMETABOLISM; ABNORMALITIES; DEGENERATION; ACCURACY AB To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an inter national workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP. RP Litvan, I (reprint author), NINCDS,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. RI Pramstaller, Peter/C-2357-2008; OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 88 TC 1261 Z9 1283 U1 1 U2 40 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1996 VL 47 IS 1 BP 1 EP 9 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA UX188 UT WOS:A1996UX18800001 PM 8710059 ER PT J AU Thinakaran, G Borchelt, DR Lee, MK Slunt, HH Spitzer, L Kim, G Ratovitsky, T Davenport, F Nordstedt, C Seeger, M Hardy, J Levey, AI Gandy, SE Jenkins, NA Copeland, NG Price, DL Sisodia, SS AF Thinakaran, G Borchelt, DR Lee, MK Slunt, HH Spitzer, L Kim, G Ratovitsky, T Davenport, F Nordstedt, C Seeger, M Hardy, J Levey, AI Gandy, SE Jenkins, NA Copeland, NG Price, DL Sisodia, SS TI Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo SO NEURON LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; PRECURSOR PROTEIN GENE; MUTATION; EXPRESSION AB The majority of early-onset cases of familial Alzheimer's disease (FAD) are linked to mutations in two related genes, PS1 and PS2, located on chromosome 14 and 1, respectively. Using two highly specific antibodies against nonoverlapping epitopes of the PS1-encoded polypeptide, termed presenilin 1 (PS1), we document that the preponderant PS1-related species that accumulate in cultured mammalian cells, and in the brains of rodents, primates, and humans are similar to 27-28 kDa N-terminal and similar to 16-17 kDa C-terminal derivatives. Notably, a FAD-linked PS1 variant that lacks exon 9 is not subject to endoproteolytic cleavage. In brains of transgenic mice expressing human PS1, similar to 17 kDa and similar to 27 kDa PS1 derivatives accumulate to saturable levels, and at similar to 1:1 stoichiometry, independent of transgene-derived mRNA. We conclude that PS1 is subject to endoproteolytic processing in vivo. 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. KAROLINSKA INST,DEPT CLIN NEUROSCI,S-17176 STOCKHOLM,SWEDEN. CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. NCI,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV,FREDERICK,MD 21701. UNIV S FLORIDA,DEPT PSYCHIAT,SUNCOAST ALZHEIMERS DIS LABS,TAMPA,FL 33613. RP Thinakaran, G (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205, USA. RI Hardy, John/C-2451-2009; Lee, Michael/D-9491-2013; Levey, Allan/F-2104-2011 OI Lee, Michael/0000-0001-5865-9682; Levey, Allan/0000-0002-3153-502X FU NIA NIH HHS [AG05689, AG11508]; NINDS NIH HHS [NS20471] NR 32 TC 863 Z9 877 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1996 VL 17 IS 1 BP 181 EP 190 DI 10.1016/S0896-6273(00)80291-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UY981 UT WOS:A1996UY98100018 PM 8755489 ER PT J AU Durell, SR Guy, HR AF Durell, SR Guy, HR TI Structural model of the outer vestibule and selectivity filter of the Shaker voltage-gated K+ channel SO NEUROPHARMACOLOGY LA English DT Article DE potassium channels; molecular models; protein structure; ion pores; scorpion toxins ID POTASSIUM CHANNELS; SECONDARY STRUCTURE; ION CONDUCTION; PORE STRUCTURE; MUTANT CYCLES; TEA BLOCKADE; MUTATIONS; REGION; RECEPTOR; PROTEINS AB A new generation of structural models were developed of the outer vestibule and ion-selective portion of the voltage-gated Shaker K+ channel. Some features of these models are similar to those that we have developed previously [Durrel S. R. and Guy H. R. (1992) Biophys. J. 62, 238-250; Guy H. R. (1990) In Monovalent Cations in Biological Systems (Pasternak C. A., Ed.), pp. 31-58, CRC Press, Boca Raton, FL; Guy Ii. R. and Durell S. R. (1994) In Molecular Evolution of Physiological processes (Fambrough D., Ed.), pp. 197-212, The Rockefeller University Press, NY; Guy H. R. and Durell S. R. (1995) In ion Channels and Genetic Diseases (Dawson D., Ed.), pp. 1-16, The Rockefeller University Press, NY] and other features were modified to make the models more consistent with recent experimental findings. The first part of the P segment is postulated, as always, to form a short alpha helix that spans only the outer portion of the membrane. The helix is tilted so that its C-terminal is nearer the pore than its N-terminal. The latter part of the P segment, P2, is postulated to have a relatively elongated conformation that is positioned approximately parallel to the axis of the pore. Four of the P2 segments assemble to form an ion-selective region that has two narrow regions; one formed by the Y445 side-chains at the outer entrance of the pore and one formed by the backbone of the T442 residues near the innermost part of the P segments. The S6 segment is postulated to form two alpha helices. The first S6 helix packs next to the P segments in our models. The NMR structures of two scorpion toxins, charybdotoxin and agitoxin 2, have been docked into the models of the outer vestibules. The shape of the outer vestibule has been modeled so that specific toxin-channel residue-residue interactions correspond to those that have been identified experimentally. C1 NCI, MATH BIOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [RR-01081] NR 55 TC 55 Z9 55 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1996 VL 35 IS 7 BP 761 EP 773 DI 10.1016/0028-3908(96)00097-4 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA VU959 UT WOS:A1996VU95900002 PM 8938709 ER PT J AU Duerson, K White, RE Jiang, F Schonbrunn, A Armstrong, DL AF Duerson, K White, RE Jiang, F Schonbrunn, A Armstrong, DL TI Somatostatin stimulates BKCa channels in rat pituitary tumor cells through lipoxygenase metabolites of arachidonic acid SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Annual Neuropharmacology Conference CY NOV 14-16, 1996 CL WASHINGTON, DC DE somatostatin; potassium channel; protein phosphatase; arachidonic acid; phospholipase A2; lipoxygenase ID ACTIVATED PROTEIN-KINASE; GTP-BINDING PROTEINS; S-K+ CHANNELS; RECEPTOR SUBTYPES; 2ND MESSENGERS; LEUKOTRIENE SYNTHESIS; PROLACTIN SECRETION; SIGNAL TRANSDUCTION; PHOSPHOLIPASE A(2); PHOSPHATASE 2A AB The stimulation of large-conductance, calcium-activated (BK) potassium channels by somatostatin through protein dephosphorylation in rat pituitary tumor cells (White et al., Nature, 351, 570-573, 1991) is blocked by drugs that interfere with arachidonic acid release by phospholipase A(2) and metabolism by 5-lipoxygenase. In contrast, higher concentrations of the same drugs had no effect on BK channel gating in cell-free patches, on the inhibition of adenylyl cyclase by somatostatin, or on the stimulation of BK channels by protein dephosphorylation through a cGMP-dependent pathway (White et al., Nature 361, 263-266, 1993). Exogenous arachidonic acid (1-20 mu M) stimulated BK channel activity through protein dephosphorylation as effectively as somatostatin and was also blocked by inhibitors of lipoxygenases but not by inhibitors of phospholipase A(2) These results support the hypothesis that lipoxygenase metabolites of arachidonic acid are second messengers linking pertussis toxin sensitive G-proteins to protein phosphatases regulating potassium channel activity (Armstrong and White, Trends Neurosci. 15, 403-408, 1992). C1 NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. WRIGHT STATE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,DAYTON,OH 45435. UNIV TEXAS,SCH MED,DEPT PHARMACOL,HOUSTON,TX 77225. FU NIDDK NIH HHS [DK 32234] NR 65 TC 58 Z9 58 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1996 VL 35 IS 7 BP 949 EP 961 DI 10.1016/0028-3908(96)00131-1 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA VU959 UT WOS:A1996VU95900018 PM 8938725 ER PT J AU Poling, JS Vicini, S Rogawski, MA Salem, N AF Poling, JS Vicini, S Rogawski, MA Salem, N TI Docosahexaenoic acid block of neuronal voltage-gated K+ channels: Subunit selective antagonism by zinc SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Annual Neuropharmacology Conference CY NOV 14-16, 1996 CL WASHINGTON, DC DE arachidonate; fatty acid; patch-clamp; zinc; potassium channel ID POLYUNSATURATED FATTY-ACIDS; RAT CEREBRAL-CORTEX; ARACHIDONIC-ACID; POTASSIUM CHANNELS; DIVALENT-CATIONS; DEPENDENT BLOCK; CELLS; BRAIN; MODULATION; CURRENTS AB The omega-3 polyunsaturated fatty acid docosahexaenoic acid is highly enriched in neuronal membranes, and several studies suggest that DHA is critical for neuronal development. We have investigated the effects of exogenously applied DHA on voltage-gated K+ channels using patch-clamp techniques. DHA produced a concentration-dependent inhibition of the sustained outward current in isolated neocortical neurons. This blocking action was examined in more detail with two cloned neuronal K+ channels (Kv1.2 and Kv3.1a) expressed in mammalian fibroblasts. DHA produced a potent inhibition of depolarization-activated K+ currents from cells expressing these channels (K-d values, 1.8 +/- 0.1 mu M and 690 +/- 60 nM, for Kv1.2 and Kv3.1a, respectively, at +40 mV). The DHA block of both channel types was rapidly reversed (similar to 2 sec) by bovine serum albumin, which binds the fatty acid. Micromolar concentrations of extracellular Zn2+ non-competitively antagonized DHA inhibition of Kv1.2 channels, whereas there was little effect on DHA block of Kv3.1a channels. Experiments with membrane patches from Kv1.2 transfected cells demonstrated that the DHA block occurred from the outside, suggesting that the fatty acid interacts directly with an external domain of the ion channel. DHA may serve as a local messenger molecule that selectively modulates the activity of certain voltage-gated K+ channels in a Zn2+-dependent fashion. Copyright (C) 1996 Elsevier Science Ltd C1 GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NINCDS,EPILEPSY RES BRANCH,NEURONAL EXCITABIL SECT,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NIAAA NIH HHS [TPAA108]; NINDS NIH HHS [K04NS01680] NR 43 TC 48 Z9 51 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1996 VL 35 IS 7 BP 969 EP 982 DI 10.1016/0028-3908(96)00127-X PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA VU959 UT WOS:A1996VU95900020 PM 8938727 ER PT J AU Poling, JS Rogawski, MA Salem, N Vicini, S AF Poling, JS Rogawski, MA Salem, N Vicini, S TI Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Annual Neuropharmacology Conference CY NOV 14-16, 1996 CL WASHINGTON, DC DE fatty acid; N-acyl-ethanolamide; recombinant potassium channel; patch clamp recording ID N-ACYLETHANOLAMINE PHOSPHOLIPIDS; DOG BRAIN PREPARATIONS; POTASSIUM A-CURRENT; HIPPOCAMPAL-NEURONS; SIGNAL-TRANSDUCTION; CALCIUM CURRENTS; RAT-BRAIN; RECEPTOR; CELLS; AGONIST AB Anandamide has been identified in porcine brain as an endogenous cannabinoid receptor ligand and is believed to be a counterpart to the psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Here we report that anandamide directly inhibits (IC50, 2.7 mu M) Shaker-related Kv1.2 K+ channels that are found ubiquitously in the mammalian brain. Delta(9)-THC also inhibited Kv1.2 channels with comparable potency (IC50, 2.4 mu M), as did several N-acyl-ethanolamides with cannabinoid receptor binding activity. Potassium current inhibition occurred through a pertussis toxin-insensitive mechanism and was not prevented by the cannabinoid receptor antagonist SR141716A. Utilizing excised patches of Kv1.2 channel-rich membrane as a rapid and sensitive bioassay, we found that phospholipase D stimulated the release of an endogenous anandamide-like K+ channel blocker from rat brain slices. Structure-activity studies were consistent with the possibility that the released blocker was either anandamide or another N-acyl-ethanolamide. Copyright (C) 1996 Elsevier Science Ltd C1 GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NINCDS,EPIDEMIOL RES BRANCH,NEURONAL EXCITABIL SECT,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NIAAA NIH HHS [TPAA108]; NINDS NIH HHS [K04NS01680] NR 31 TC 90 Z9 93 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1996 VL 35 IS 7 BP 983 EP 991 DI 10.1016/0028-3908(96)00130-X PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA VU959 UT WOS:A1996VU95900021 PM 8938728 ER PT J AU Matochik, JA Rumsey, JM Zametkin, AJ Hamburger, SD Cohen, RM AF Matochik, JA Rumsey, JM Zametkin, AJ Hamburger, SD Cohen, RM TI Neuropsychological correlates of familial attention-deficit hyperactivity disorder in adults SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE attention deficit; hyperactivity; neuropsychological tests; Wisconsin Card Sort; Wechsler Adult Intelligence Scale-Revised ID MINIMAL BRAIN-DYSFUNCTION; PSYCHIATRIC STATUS; BOYS; CHILDREN AB To determine the neuropsychological correlates of attention-deficit hyperactivity disorder (ADHD) in adults, we examined 21 subjects (16 males, 5 females) with childhood-onset and familial ADHD (i.e., biological parents of children with ADHD) with the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Wide Range Achievement Test-Revised (WRAT-R), Gray Oral Reading Test, and the Wisconsin Card Sorting Test. Consistent with findings in children with ADHD, Freedom from Distractibility (Arithmetic and Digit Span subtests) was decreased relative to the Verbal Comprehension and Perceptual Organization factors on the WAIS-R for the group as a whole, with seven subjects (33%) demonstrating significant attentional deficits when either factor or individual subtest profiles were considered. Although six men (29% of sample) met regression-based criteria for reading/spelling disabilities, only two of these subjects showed absolute deficits in reading and spelling. None showed a comorbid arithmetic disorder. Wisconsin Card Sort performance fell within normal limits for all but three subjects. The lack of significant deficits on our test battery suggest that future studies should address test sensitivity issues and include a broader assessment of the impact of ADHD symptoms on daily social functioning in adults. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Matochik, JA (reprint author), NIMH,SECT CLIN BRAIN IMAGING,CEREBRAL METAB LAB,BLDG 36,ROOM 1A05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1996 VL 9 IS 3 BP 186 EP 191 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA UR707 UT WOS:A1996UR70700007 ER PT J AU Kirkby, BS VanHorn, JD Ostrem, JL Weinberger, DR Berman, KF AF Kirkby, BS VanHorn, JD Ostrem, JL Weinberger, DR Berman, KF TI Cognitive activation during PET: A case study of monozygotic twins discordant for closed head injury SO NEUROPSYCHOLOGIA LA English DT Article DE regional cerebral blood flow; frontal lobe; recovery of function; hippocampus; working memory; Wisconsin Card Sorting Test ID CEREBRAL BLOOD-FLOW; CONTUSION INDEX; DYSFUNCTION; TOMOGRAPHY; RECOVERY; CORTEX; BRAIN AB Using positron emission tomography (PET), we studied physiological changes in a patient with frontal lobe damage resulting from closed head injury by assessing his regional cerebral blood flow (rCBF) pattern relative to that of his uninjured monozygotic (MZ) cotwin and against normal variability between cotwins in 10 comparably-aged, uninjured MZ twin pairs. rCBF was measured during the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Differences between the index twins in rCBF activation (WCST-control) in regions determined on coplanar MRIs were compared to within pair differences in the control group using the Z-statistic. Activation differences between the index twins extending beyond normal variability were found in two regions-relative to his uninjured cotwin, the injured twin showed less activation in the inferior portion of the left inferior frontal gyrus while showing greater activation in the left hippocampus (P < 0.04). This pattern contrasts with that of normal subjects during WCST performance of augmented rCBF in the prefrontal cortex and not in the hippocampus. These rCBF differences appear to reflect the utilization of different neural systems when performing a frontal-lobe task. The use of the hippocampus by the injured twin might reflect an attempt to compensate for compromised frontal lobe functioning. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NR 31 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUL PY 1996 VL 34 IS 7 BP 689 EP 697 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA UQ417 UT WOS:A1996UQ41700007 PM 8783220 ER PT J AU Oren, DA AF Oren, DA TI Humoral phototransduction: Blood is a messenger SO NEUROSCIENTIST LA English DT Article DE circadian rhythms; hemoglobin; light; nitric oxide; carbon monoxide; bile pigments; seasonal affective disorder; psychiatric disorders ID NITRIC-OXIDE; CARBON-MONOXIDE; LIGHT; MELATONIN; MEDIATION; BILIRUBIN; HUMANS AB Drawing upon the premise that there is a parsimony to nature, the author proposes that heme moieties and bile pigments in animals mediate some non-visual influences of light upon neuroactive gases and biological rhythms. Primary abnormalities in synthesis and regulation of blood and bile may, therefore, cause some neuropsychiatric illnesses. Light may play a critical role in neurotransmission. C1 NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,CLIN PSYCHOBIOL MOOD DISORDERS PROGRAM,ROCKVILLE,MD 20857. NR 38 TC 45 Z9 48 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JUL PY 1996 VL 2 IS 4 BP 207 EP 210 DI 10.1177/107385849600200408 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VX114 UT WOS:A1996VX11400008 ER PT J AU Hyman, SE AF Hyman, SE TI Regulation of gene expression by neural signals SO NEUROSCIENTIST LA English DT Review DE transcriptional regulation; signaling; CREB; Fos; AP-1 ID CAMP-RESPONSIVE ELEMENT; TRANSCRIPTION FACTOR CREB; DEPENDENT PROTEIN-KINASE; LEUCINE ZIPPER PROTEINS; C-FOS TRANSCRIPTION; TRANS-ACTING FACTOR; LONG-TERM-MEMORY; CYCLIC-AMP; SOMATOSTATIN GENE; NUCLEAR-PROTEIN AB Regulation of gene expression by extracellular signals is a ubiquitous biological mechanism controlling cell proliferation, differentiation, homeostasis, and adaptation to the environment. This article will focus on one set of issues within the broad topic of regulated gene expression: mechanisms by which neurotransmitters and neural activity regulate genes within the mature nervous system. The regulatory actions of growth factors, cytokines, and other types of extracellular signals are complex matters deserving separate review. This article proceeds from a basic overview of transcriptional regulation to a more specific discussion of the actions of two families of transcriptional regulators, the CREB family and the AP-1 family. These families of proteins are discussed because they play a central role in the regulation of gene expression by neurotransmitters and also because they exemplify many general principles of extracellular signal-regulated gene expression. C1 NIMH,ROCKVILLE,MD 20857. NR 43 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JUL PY 1996 VL 2 IS 4 BP 217 EP 224 DI 10.1177/107385849600200410 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VX114 UT WOS:A1996VX11400010 ER PT J AU Blair, A Hayes, RB Stewart, PA Zahm, SH AF Blair, A Hayes, RB Stewart, PA Zahm, SH TI Occupational epidemiologic study design and application SO OCCUPATIONAL MEDICINE-STATE OF THE ART REVIEWS LA English DT Review ID NON-HODGKINS-LYMPHOMA; STANDARDIZED MORTALITY RATIOS; ASCERTAINING FRIEND CONTROLS; AGRICULTURAL RISK-FACTORS; LUNG-CANCER; FORMALDEHYDE EXPOSURE; BREAST-CANCER; DEAD CONTROLS; SAMPLE-SIZE; PESTICIDE USE RP Blair, A (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,OCCUPAT EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 113 TC 9 Z9 9 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0885-114X J9 OCCUP MED JI Occup. Med.-State Art Rev. PD JUL-SEP PY 1996 VL 11 IS 3 BP 403 EP 419 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VJ581 UT WOS:A1996VJ58100004 PM 8887376 ER PT J AU Liao, Y Tang, ZY Liu, KD Ye, SL Li, J Huang, Z Wang, DB Segal, DM AF Liao, Y Tang, ZY Liu, KD Ye, SL Li, J Huang, Z Wang, DB Segal, DM TI Preparation and application of anti-HBx/anti-CD3 bispecific monoclonal antibody (BsAb) retargeting effector cells for lysis of human hepatoma xenografts in nude mice SO ONCOLOGY REPORTS LA English DT Article DE hepatoma; HBxAg; bispecific monoclonal antibody; effector cells; apoptosis; in situ end-labeling (ISEL) ID HEPATITIS-B VIRUS; PERIPHERAL-BLOOD LYMPHOCYTES; HEPATOCELLULAR-CARCINOMA; T-CELLS; BIFUNCTIONAL ANTIBODIES; CELLULAR IMMUNOTHERAPY; HYBRID HYBRIDOMAS; TARGET-CELL; CANCER; GENE AB Evidence indicated that the x gene of human HBV can cause cancer in transgenic mice, moreover, HBxAg was so far the most frequent and strong antigen among those HBV markers expressed in hepatocellular carcinoma (HCC) tissues. Aiming to enhance killing of HCC by effector cells, we established an anti-HBx/anti-CD3 hybrid-hybridomas by fusion of anti-HBx hybridoma cells with FITC-labeled anti-CD3 HAT sensitive cells, and followed by FACStar sterile cell sorting, HAT selection and eventually verified by ELISA and double bridging assay. Using two color cytometric analysis, we found that bispecific monoclonal antibody (BsAb) remarkably enhanced in vitro effector-target cell conjugates (48.3% vs. 8.5%). In in vivo study, BsAb retargeting effector cells were significantly more effective than that of effector cells alone in shrinkage of LTNM4 HCC xenografts (HBxAg positive) in nude mice, not only in fresh inoculated tumors but also in established tumors (p<0.01, p<0.01, respectively). Besides, pronounced apoptotic cell death and infiltration of lymphocytes in the peripheral of tumor nodules can also be witnessed in the tissues treated by BsAb plus effector cells, but not in the controls. The results demonstrated that antiHBx/anti-CD3 BsAb was able to redirect effector cells for lysis of HBxAg positive HCC cells both in vitro and in vivo and it also indicated that shrinkage of tumors in nude mice with therapy of BsAb retargeting effector cells was partially due to initiation of apoptotic cell death. C1 SHANGHAI MED UNIV, LIVER CANC INST, SHANGHAI 200032, PEOPLES R CHINA. SHANGHAI MED UNIV, TUMOR HOSP, SHANGHAI 200032, PEOPLES R CHINA. CHINESE ACAD MED SCI, DEPT IMMUNOL, BEIJING 100021, PEOPLES R CHINA. NCI, IMMUNOTARGETING THERAPY SECT, BETHESDA, MD 21298 USA. NR 60 TC 2 Z9 3 U1 1 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JUL-AUG PY 1996 VL 3 IS 4 BP 637 EP 644 PG 8 WC Oncology SC Oncology GA UT759 UT WOS:A1996UT75900007 PM 21594426 ER PT J AU Bettelheim, FA Zigler, JS AF Bettelheim, FA Zigler, JS TI Degradation of vimentin in frozen rat lenses SO OPHTHALMIC RESEARCH LA English DT Article DE frozen storage; protein degradation; rat lens; vimentin ID CATARACT FORMATION; BETA-CRYSTALLINS; CALPAIN-II; PROTEINS; MODEL AB Rat lenses stored for extended periods at -20 degrees C showed degradation and eventual disappearance of vimentin. This may have been caused by the rupture of cells and/or organelles by growing ice crystals and the subsequent release and diffusion of proteases, Besides the disappearance of vimentin there was also a decrease in the intensity of the beta B1 polypeptide after 3 months storage, The observations reported herein are generally qualitative in nature, but should serve to alert other investigators of a potential problem. C1 NEI,NIH,BETHESDA,MD 20892. RP Bettelheim, FA (reprint author), ADELPHI UNIV,DEPT CHEM,GARDEN CITY,NY 11530, USA. FU NEI NIH HHS [EY-02751] NR 13 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PD JUL-AUG PY 1996 VL 28 IS 4 BP 219 EP 223 PG 5 WC Ophthalmology SC Ophthalmology GA VF143 UT WOS:A1996VF14300003 PM 8878184 ER PT J AU Whitcup, SM Csaky, KG Podgor, MJ Chew, EY Perry, CH Nussenblatt, RB AF Whitcup, SM Csaky, KG Podgor, MJ Chew, EY Perry, CH Nussenblatt, RB TI A randomized, masked, crossover trial of acetazolamide for cystoid macular edema in patients with uveitis SO OPHTHALMOLOGY LA English DT Article ID VISUAL-ACUITY; VITRECTOMY; THERAPY; EYE AB Purpose: To study the effect of acetazolamide on cystoid macular edema in patients with uveitis. Methods: Forty patients with chronic intermediate, posterior, or panuveitis associated cystoid macular edema were randomized into a masked, cross-over trial comparing acetazolamide versus placebo. Patients received an initial 4-week course of either acetazolamide or placebo (course A) followed by a 4-week washout period. They then received a 4-week course of the opposite study medication (course B). Primary endpoints included area of cystoid macular edema measured on late-phase views of fluorescein angiography and visual acuity. Results: Thirty-seven patients completed the trial and were available for analysis; 17 (46%) were randomized to receive acetazolamide and 20 (54%) to receive placebo during course A. Acetazolamide resulted in a 0.5-disc area (25%) decrease in cystoid macular edema over that of placebo (P = 0.01; estimated treatment effect = -0.5 disc areas; 95% confidence interval, -0.9 to -0.1). However, there was no statistically significant effect of acetazolamide on visual acuity (P = 0.61; estimated treatment effect = 0.6 letters; 95% confidence interval, -2 to 3). Conclusions: A 4-week course of acetazolamide therapy results in a statistically significant but small decrease in cystoid macular edema in patients with chronic uveitis, and does not improve visual acuity. In contrast to previous studies in the literature, acetazolamide may have a more limited clinical benefit in patients with long-standing cystoid macular edema associated with chronic uveitis. RP Whitcup, SM (reprint author), NEI,NIH,10 CTR DR,BLDG 10,RM 10N 202,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z99 EY999999] NR 35 TC 48 Z9 49 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1996 VL 103 IS 7 BP 1054 EP 1062 PG 9 WC Ophthalmology SC Ophthalmology GA UY313 UT WOS:A1996UY31300018 PM 8684794 ER PT J AU Chen, RM Lupski, JR Greenberg, F Lewis, RA AF Chen, RM Lupski, JR Greenberg, F Lewis, RA TI Ophthalmic manifestations of Smith-Magenis syndrome SO OPHTHALMOLOGY LA English DT Article ID CONTIGUOUS-GENE SYNDROME; INTERSTITIAL DELETION; (17)(P11.2P11.2) AB Purpose: The Smith-Magenis syndrome (SMS) is a multiple-anomaly, mental retardation syndrome associated with deletions of a contiguous region of chromosome 17p11.2. Prior reports have described ophthalmic anomalies with SMS, including telecanthus, ptosis, strabismus, myopia, iris anomalies, cataracts, optic nerve hypoplasia, and retinal detachment. This report defines the ophthalmic spectrum in 28 individuals with SMS subjected to a multidisciplinary clinical and molecular survey. Methods: Individuals with deletion of chromosome 17p11.2 detected by high-resolution cytogenetic analysis underwent complete ophthalmologic evaluation comprised of ophthalmic history, visual acuity, cycloplegic refraction, motility, and biomicroscopic and ophthalmoscopic examination. Results: Among the 28 subjects, ranging in age from 0.8 to 29.3 years, the most frequent ocular findings were iris anomalies (68%), microcornea (50%), myopia (42%), and strabismus (32%). Bilateral microphthalmos with uveal and retinal coloboma was observed in one individual. No subject had cataract or retinal detachment. Conclusions: This is the largest single-center series of subjects with SMS that includes ophthalmic evaluation. As in prior reports, iris anomalies and strabismus were observed, but microcornea had not been noted previously. The absolute refractive error was hypermetropic in half of these subjects. Cataract, ptosis, and retinal pathology, including detachment, were not observed in any subject. All individuals with SMS should be evaluated by an ophthalmologist, with special attention to strabismus, microcornea, iris anomalies, and refractive errors. C1 BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. FU NCRR NIH HHS [M01 RR-00188] NR 29 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1996 VL 103 IS 7 BP 1084 EP 1091 PG 8 WC Ophthalmology SC Ophthalmology GA UY313 UT WOS:A1996UY31300024 PM 8684798 ER PT J AU Bunin, GR Feuer, EJ Witman, PA Meadows, AT AF Bunin, GR Feuer, EJ Witman, PA Meadows, AT TI Increasing incidence of childhood cancer: Resort of 20 years experience from the Greater Delaware Valley Pediatric Tumor Registry SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID MALIGNANT BRAIN-TUMORS; UNITED-STATES; TRENDS AB As little is known about the aetiology of cancer in children, analysis of time trends may be useful. Recent data on time trends for paediatric cancers are very limited. We report here on trends in the incidence of 15 categories of cancer in children under 15 years of age from 1970 to 1989, using data from the Greater Delaware Valley Pediatric Tumor Registry in the US. Total cancer incidence increased 1% per year (P < 0.001). Neither acute lymphocytic leukaemia, acute myelocytic leukaemia, nor total leukaemia incidence changed significantly. In contrast, the incidence of central nervous system (CNS) tumours rose 2.7% per year (P < 0.001). All three subgroups of this category, glioma, primitive neuroectodermal tumour (PNET)/medulloblastoma, and other CNS tumours, showed increases. For glioma and PNET/medulloblastoma, trends differed by age, race, and/or gender. Among the other childhood cancers, significant increases were observed for non-Hodgkin lymphoma and neuroblastoma. For osteosarcoma and retinoblastoma, no overall change in incidence was observed, although decreases were observed in some age and race subgroups. The rise in CNS tumour incidence confirms previous reports from the US and Great Britain. The lack of change for acute lymphocytic leukaemia conflicts with other data from the US, but diagnostic changes appear to explain at least part of the discrepancy. The increase in neuroblastoma has also been observed in Great Britain. In contrast to our finding, investigators in the US and Great Britain have reported no rise in non-Hodgkin lymphoma. Analyses for more of the childhood cancers from other registries would aid in detecting and interpreting incidence trends in recent years. C1 UNIV PENN,CHILDRENS HOSP PHILADELPHIA,DIV BIOSTAT & EPIDEMIOL,PHILADELPHIA,PA 19104. NCI,SURVEILLANCE PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,DIV CHRON DIS EPIDEMIOL,NEW HAVEN,CT 06510. RP Bunin, GR (reprint author), UNIV PENN,CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,DIV ONCOL,34TH ST & CIV CTR BLVD,PHILADELPHIA,PA 19104, USA. NR 20 TC 44 Z9 46 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 1996 VL 10 IS 3 BP 319 EP 338 DI 10.1111/j.1365-3016.1996.tb00054.x PG 20 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA UV772 UT WOS:A1996UV77200008 PM 8822774 ER PT J AU Baldwin, RL Kobrin, MS Tran, T Pastan, I Korc, M AF Baldwin, RL Kobrin, MS Tran, T Pastan, I Korc, M TI Cytotoxic effects of TGF-alpha-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells SO PANCREAS LA English DT Article DE TP40; growth inhibition; epidermal growth factor receptor ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; CANCER; EXPRESSION; BINDING; AERUGINOSA; BLADDER; TUMORS; ASSAY AB The epidermal growth factor (EGF) receptor is overexpressed in human pancreatic cancers and cultured cell lines. TP40 is a chimeric protein composed of transforming growth factor-alpha (TGF-alpha) linked to a modified Pseudomonas exotoxin A (PE40) that exerts growth inhibitory effects on cells bearing a high number of EGF receptors. Therefore, we compared the effect of TP40 on the growth of Chinese hamster ovary (CHO) cells expressing varying levels of the EGF receptor and on the growth of two human pancreatic cancer cell lines. The growth of CHO cells devoid of endogenous EGF receptors was minimally altered by high concentrations of TP40, even following a 72-h incubation period. In contrast, in CHO cells expressing similar to 95,000 and 438,000 EGF receptors per cell, one-half maximal growth inhibition occurred at 5 and 3 ng/ml TP40, respectively. Following a 72-h incubation in T3M4 and COLO 357 human pancreatic cancer cells, one-half maximal growth inhibition occurred at 0.2 and 0.4 ng/ml TP40, respectively. This effect was significantly greater than that of native Pseudomonas exotoxin A. These findings indicate that human pancreatic cancer cells are markedly sensitive to the growth inhibitory effects of TP40 and raise the possibility that TP40 may have a therapeutic role in this disorder. C1 UNIV CALIF IRVINE,DEPT MED,DIV ENDOCRINOL DIABET & METAB MED SCI 1,IRVINE,CA 92717. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-40162] NR 36 TC 13 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 1996 VL 13 IS 1 BP 16 EP 21 DI 10.1097/00006676-199607000-00002 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UQ720 UT WOS:A1996UQ72000002 PM 8783329 ER PT J AU Perfetti, R Henderson, TE Wang, YH MontroseRafizadeh, C Egan, JM AF Perfetti, R Henderson, TE Wang, YH MontroseRafizadeh, C Egan, JM TI Insulin release and insulin mRNA levels in rat islets of Langerhans cultured on extracellular matrix SO PANCREAS LA English DT Article DE islets of Langerhans; matrigel; insulin; glucagon; somatostatin ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; PANCREATIC BETA-CELLS; BASEMENT-MEMBRANE; DIFFERENTIATION; LAMININ; MICE; AGE; GROWTH; GENE AB Primary culture of rat islets of Langerhans lose glucose responsiveness and eventually die when cultured for a long period of time, In this study we evaluated the effect of matrigel, a basement membrane extract, on (i) islet cell survival, (ii) cell responsiveness following a glucose challenge, and (iii) mRNA levels for insulin, glucagon, and somatostatin. Pancreatic islets were isolated by collagenase digestion and plated in culture dishes either coated or not with a matrigel layer. Using the reverse hemolytic plaque assay, we determined the total number of insulin-secreting cells and the amount of insulin secreted by individual beta cells, After 1 h of exposure to 5 mM glucose, beta cells from 6-month-old rat islets cultured for 6 weeks on matrigel showed an equal number of insulin-secreting cells compared to freshly isolated islets cultured for only 3 days in the absence of matrigel (39.5 +/- 2.5 vs, 37.1 +/- 2.6%). Furthermore, the release of insulin by cells cultured on matrigel for 6 weeks increased in a glucose-dependent manner (p < 0.001) and showed an ED(50) of 7 mM. However, the amount of insulin released per single beta cell was reduced by 40-60% (p < 0.02) compared to that released from isolated beta cells derived from a 3-day culture of islets, Finally, there was a 35-55% increase (p < 0.05) in the levels of insulin, glucagon, and somatostatin mRNAs in cells cultured for 6 weeks on matrigel. These data suggest a trophic effect of matrigel on the maintenance of normal beta-cell activity and function acid may lead the way to the development of a new model for the study of pancreatic islets in long-term culture. RP Perfetti, R (reprint author), NIA,NIH,DIABET UNIT,LAB CLIN PHYSIOL,GERONTOL RES CTR,ROOM 2B02,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 36 TC 31 Z9 31 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 1996 VL 13 IS 1 BP 47 EP 54 DI 10.1097/00006676-199607000-00006 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UQ720 UT WOS:A1996UQ72000006 PM 8783333 ER PT J AU Broder, CC Dimitrov, DS AF Broder, CC Dimitrov, DS TI HIV and the 7-transmembrane domain receptors SO PATHOBIOLOGY LA English DT Review DE HIV-1; receptors; chemokines; fusion ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOATTRACTANT PROTEIN-1 RECEPTOR; TISSUE-SPECIFIC EXPRESSION; CC-CHEMOKINE RECEPTOR; HUMAN CD4 GENE; ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; CD26 ANTIGEN AB The recent discovery of a chemokine receptor, fusin (fusin/CXCR-4), as the long-sought human immunodeficiency virus type 1 (HIV-1) coreceptor opened an entirely new field of aquired immunodeficiency syndrome (AIDS) research on mechanisms of viral entry, tropism and pathogenesis. It was soon followed by the identification of the chemokine receptor CCR-5 as the major macrophage-tropic (M-tropic) HIV-1 coreceptor and the demonstration that other chemokine receptors, CCR-3 and CCR-2b, also may serve as coreceptors, albeit at somewhat lower efficiency. Very recently it was demonstrated that the mechanism of the coreceptor function involves the formation of a complex on the cell surface between the HIV-1 envelope, the primary receptor CD4 and the coreceptor. Thus the prevention of the HIV-1 envelope glycoprotein-mediated fusion by the chemokines RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta, as well as by the recently identified fusin/CXCR-4 ligand, stromal cell-derived factor-1 (SDF-1) could be explained by disruption of that complex. Interestingly, the identification of the HIV-1 coreceptor CCR-5 not only provided new insights into the mechanisms of viral entry and tropism, but also may help in explaining why some people with genetic alterations in CCR-5 are protected from HIV-1 infection. C1 NCI, NIH, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. RP Broder, CC (reprint author), UNIFORMED SERV UNIV HLTH SCI, DEPT MICROBIOL & IMMUNOL, 4301 JONES BRIDGE RD, BETHESDA, MD 20814 USA. NR 108 TC 57 Z9 58 U1 2 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JUL-AUG PY 1996 VL 64 IS 4 BP 171 EP 179 DI 10.1159/000164032 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA WF931 UT WOS:A1996WF93100001 PM 9031325 ER PT J AU Messina, E Muhlhauser, J Giuliano, M Pandolfi, A Morgese, G Procopio, A AF Messina, E Muhlhauser, J Giuliano, M Pandolfi, A Morgese, G Procopio, A TI Surfactant protein a-producing cells in human fetal lung are good targets for recombinant adenovirus-mediated gene transfer SO PEDIATRIC RESEARCH LA English DT Article ID GLUCOCORTICOID REGULATION; CYSTIC-FIBROSIS; II CELLS; EXPRESSION; HYPEROXIA; INJURY; DIFFERENTIATION; EPITHELIUM; INDUCTION; THERAPY AB Local delivery of Escherichia coli beta-galactosidase gene (beta-gal) to surfactant protein-A (SP-A)-producing cells by a replication-defective recombinant adenovirus (AdCMV.beta-gal) was tested in human 8-12-wk-old fetal lung explants cultured in Waymouth's medium. In contrast to uninfected explants, direct addition of 0.8-1.6 x 10(6) plaque-forming units of AdCMV.beta-gal resulted in beta-galactosidase (beta-Gal)-specific staining of the pulmonary epithelium. SP-A localization by indirect immunofluorescence showed positive specific staining of the beta-Gal(+) lung epithelial cells, demonstrating that recombinant-defective adenoviruses efficiently transfer reporter genes to fetal lung SP-A(+) cells. The reporter gene expression in SPA(+) cells persisted for more than 1 mo. No apparent alteration of morphology, phenotype, and growth was observed. The in vitro human lung model described may be useful for testing DNA constructs for vector-mediated gene therapy, as an approach to the treatment of congenital defects and neonatal disorders, such as respiratory distress syndrome and bronchopulmonary dysplasia. C1 UNIV G DANNUNZIO, EXPTL CTR GENE THERAPY & DIAGNOSIS, CHIETI, ITALY. UNIV G DANNUNZIO, DIV PHYSIOPATHOL, CHIETI, ITALY. UNIV G DANNUNZIO, DIV PEDIATRY, CHIETI, ITALY. NIA, CARDIOVASC SCI LAB, GENE THERAPY UNIT, NIH, BALTIMORE, MD USA. IST DERMOPAT IMMACOLATA, ROME, ITALY. RI pandolfi, assunta/K-4595-2016 OI pandolfi, assunta/0000-0003-4135-7631 NR 46 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD JUL PY 1996 VL 40 IS 1 BP 142 EP 147 DI 10.1203/00006450-199607000-00024 PG 6 WC Pediatrics SC Pediatrics GA UT559 UT WOS:A1996UT55900024 PM 8798260 ER PT J AU Schreiber, GB Robins, M StriegelMoore, R Obarzanek, E Morrison, JA Wright, DJ AF Schreiber, GB Robins, M StriegelMoore, R Obarzanek, E Morrison, JA Wright, DJ TI Weight modification efforts reported by black and white preadolescent girls: National Heart, Lung, and Blood Institute Growth and Health Study SO PEDIATRICS LA English DT Article DE gain weight, lose weight; black; white; preadolescent girls; body mass index ID ADOLESCENT GIRLS; UNITED-STATES; EATING ATTITUDES; CHILDHOOD WEIGHT; SCHOOL-STUDENTS; BODY-MASS; OBESITY; BEHAVIOR; CHILDREN; ADULTS AB Objective. This study tested four hypotheses: (1) a high percentage of 9- and 10-year-old girls are already trying to lose weight; (2) more white than black girls are trying to lose weight; (3) more black than white girls are trying to gain weight; and (4) weight modification efforts of preadolescent girls are influenced by factors other than race, such as maternal criticism, body dissatisfaction, and socioeconomic status. Design. Cross-sectional analysis of baseline data on 2379 girls 9 and 10 years of age, which consisted of 1213 black and 1166 white enrollees. Results. Black girls were taller and heavier and showed earlier signs of puberty than white girls but were less dissatisfied with their weight, body shape, and body parts. Approximately 40% of 9- and 10-year-old girls reported that they were trying to lose weight. Of those girls classified in the fourth quartile of body mass index (BMI), approximately 75% were trying to lose weight. After adjusting for BMI, no significant black and white differences in the prevalence of those trying to lose weight were seen, but significantly more black than white girls were trying to gain weight. Multiple logistic regression identified a high BMI, the mother telling her she was too fat, and body dissatisfaction as the major factors associated with trying to lose weight. However, chronic dieting was only associated with a high BMI and the mother telling her she was too fat. An important predictor of girls who were trying to gain weight was being black, along with having a low BMI and the mother telling her she was too thin. Conclusions. Attempts at gaining weight are much more frequent among black preadolescent girls than their white counterparts. No racial difference was found between black and white girls in their efforts to lose weight or to practice chronic dieting. Because approximately 40% of 9- and 10-year-old girls are already trying to lose weight, pediatricians should capitalize on this concern by providing information on proper weight control techniques. Educational efforts should be directed to both the mother and the child, because weight control efforts of preadolescent girls are stimulated by their mothers' admonitions of being too fat or too thin. The high prevalence of dieting among the thinnest preadolescent girls also needs to be addressed by pediatricians. C1 WESLEYAN UNIV,DEPT PSYCHOL,MIDDLETOWN,CT 06457. NHLBI,BETHESDA,MD 20892. CHILDRENS HOSP,MED CTR,DIV CARDIOL,CINCINNATI,OH. RP Schreiber, GB (reprint author), WESTAT CORP,1441 W MONTGOMERY AVE,WB 272,ROCKVILLE,MD 20850, USA. FU NHLBI NIH HHS [HC-55025, HC-55024, HC-55023] NR 48 TC 68 Z9 69 U1 4 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 63 EP 70 PG 8 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700011 PM 8668414 ER PT J AU Oh, W Blackmon, LR Escobedo, M Fanaroff, AA Kirkpatrick, BV Light, IJ MacDonald, HM Papile, LA Shoemaker, CT Conner, GK Martin, JN McMillan, DB Rowley, D Wright, LL Langer, JC Mennuti, MT Gilstrap, LC Hall, GP Heyl, PS Hoskins, IA Maeder, EC Phelan, ST Hawkins, JL AF Oh, W Blackmon, LR Escobedo, M Fanaroff, AA Kirkpatrick, BV Light, IJ MacDonald, HM Papile, LA Shoemaker, CT Conner, GK Martin, JN McMillan, DB Rowley, D Wright, LL Langer, JC Mennuti, MT Gilstrap, LC Hall, GP Heyl, PS Hoskins, IA Maeder, EC Phelan, ST Hawkins, JL TI Use and abuse of the Apgar Score SO PEDIATRICS LA English DT Article ID CEREBRAL-PALSY; ASPHYXIA AB This is a revised statement published jointly with the American College of Obstetricians and Gynecologists that emphasizes the appropriate use of the Apgar Score. The highlights of the statement include: (1) the Apgar Score is useful in assessing the condition of the infant at birth; (2) the Apgar score alone should not be used as evidence that neurologic damage was caused by hypoxia that results in neurologic injury or from inappropriate intrapartum treatment; and (3) an infant who has had ''asphyxia'' proximate to delivery that is severe enough to result in acute neurologic injury should demonstrate all of the following: (a) profound metabolic or mixed acidemia (pH <7.00) on an umbilical arterial blood sample, if obtained, (b) an Apgar score of 0 to 3 for longer than 5 minutes, (c) neurologic manifestation, eg, seizure, coma, or hypotonia, and (d) evidence of multiorgan dysfunction. C1 AMER COLL OBSTETRICIANS & GYNECOLOGISTS,COMM OBSTET PRACTICE,WASHINGTON,DC 20024. AMER NURSES ASSOC,WASHINGTON,DC 20024. ASSOC WOMENS HLTH OBSTET & NEONATAL NURSES,WASHINGTON,DC 20005. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NICHHD,BETHESDA,MD 20892. AMER ACAD PEDIAT,SECT SURG,ELK GROVE VILLAGE,IL 60009. AMER SOC ANESTHESIOLOGISTS,PARK RIDGE,IL 60068. RP Oh, W (reprint author), AMER ACAD PEDIAT,COMM FETUS & NEWBORN,POB 927,ELK GROVE VILLAGE,IL 60009, USA. NR 11 TC 85 Z9 91 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 141 EP 142 PG 2 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700030 ER PT J AU Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Hoskins, IA Mulinare, J Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ AF Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Hoskins, IA Mulinare, J Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ TI Unapproved uses of approved drugs: The physician, the package insert, and the food and drug administration: Subject review SO PEDIATRICS LA English DT Article C1 AMER MED ASSOC,CHICAGO,IL 60610. US PHARMACOPEIA CONVENT,ROCKVILLE,MD 20852. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. PHARMACEUT RES & MANUFACTURERS ASSOC AMER,WASHINGTON,DC. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. AMER ACAD PEDIAT,SECT ANESTHESIOL,ELK GROVE VILLAGE,IL 60009. AMER ACAD PEDIAT,SECT ALLERGY & IMMUNOL,ELK GROVE VILLAGE,IL 60009. AMER ACAD PEDIAT,COMM DRUGS,ELK GROVE VILLAGE,IL 60009. NR 0 TC 52 Z9 52 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 JUL PY 1996 VL 98 IS 1 BP 143 EP 145 PG 3 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700031 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Hadler, S Orenstein, WA Rabinovich, NR AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Hadler, S Orenstein, WA Rabinovich, NR TI Recommended Childhood Immunization Schedule SO PEDIATRICS LA English DT Article C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. US FDA,WASHINGTON,DC 20204. NATL VACCINE PROGRAM OFF,ROCKVILLE,MD. AMER THORAC SOC,NEW YORK,NY. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. NIH,BETHESDA,MD 20892. RP Halsey, NA (reprint author), AMER ACAD PEDIAT,COMM INFECT DIS,POB 927,ELK GROVE VILLAGE,IL 60009, USA. NR 3 TC 2 Z9 2 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 JUL PY 1996 VL 98 IS 1 BP 158 EP 160 PG 3 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700035 ER PT J AU Rhoads, GG Rogan, WJ AF Rhoads, GG Rogan, WJ TI Treatment of lead-exposed children SO PEDIATRICS LA English DT Letter C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Rhoads, GG (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08855, USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 162 EP 163 PG 2 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700038 PM 8668397 ER PT J AU Kattwinkel, J Brooks, J Keenan, ME Malloy, M Willinger, M AF Kattwinkel, J Brooks, J Keenan, ME Malloy, M Willinger, M TI ''Back to sleep'' program - Reply SO PEDIATRICS LA English DT Letter C1 NICHHD,BETHESDA,MD 20892. RP Kattwinkel, J (reprint author), AMER ACAD PEDIAT,TASK FORCE INFANT SLEEPING POSIT & SIDS,ELK GROVE VILLAGE,IL 60007, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 165 EP 165 PG 1 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700042 ER PT J AU Newman, TB Klebanoff, MA Maisels, MJ AF Newman, TB Klebanoff, MA Maisels, MJ TI Bilirubin problem - The debate continues SO PEDIATRICS LA English DT Letter ID HYPERBILIRUBINEMIA C1 NICHHD,BETHESDA,MD. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI. RP Newman, TB (reprint author), UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143, USA. NR 11 TC 1 Z9 1 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 JUL PY 1996 VL 98 IS 1 BP 165 EP 166 PG 2 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700043 PM 8668399 ER PT J AU Joseph, JS Optican, LM AF Joseph, JS Optican, LM TI Involuntary attentional shifts due to orientation differences SO PERCEPTION & PSYCHOPHYSICS LA English DT Article ID ABRUPT VISUAL ONSETS; SELECTIVE ATTENTION; PERCEPTUAL SELECTIVITY; TEXTURE SEGREGATION; NEURONAL RESPONSES; CONTROL SETTINGS; FOCAL ATTENTION; POP-OUT; MONKEY; CAPTURE AB We tested the ability of orientation differences to cause involuntary shifts of visual attention and found that these attentional shifts can occur in response to an orientation ''pop-out'' display. Texture-like cue stimuli consisting of discrete oriented bars, with either uniform orientation or containing a noninformative orthogonally oriented bar, were presented for a variable duration. Subsequent to or partially coincident with the cue stimulus was the target display of a localization or two-interval forced-choice task, followed by a mask display. Naive subjects consistently showed greater accuracy in trials with the target at the location of the orthogonal orientation compared with trials with uniformly oriented bars, with only 100 msec between the cue and mask onsets. Discriminating these orientations required a stimulus onset asynchrony (SOA) of 50-70 msec. The attentional facilitation is transient, in most cases absent, with a cue-mask SOA of 250 msec. These results suggest that the preattentive character of some texture discrimination tasks with SOAs of only 100 msec is vitiated by the involuntary attentional shifts that are caused by orientation differences. C1 NEI,NIH,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. NR 62 TC 59 Z9 60 U1 2 U2 4 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0031-5117 J9 PERCEPT PSYCHOPHYS JI Percept. Psychophys. PD JUL PY 1996 VL 58 IS 5 BP 651 EP 665 DI 10.3758/BF03213098 PG 15 WC Psychology; Psychology, Experimental SC Psychology GA UT750 UT WOS:A1996UT75000001 PM 8710445 ER PT J AU Berezhkovskii, AM Weiss, GH AF Berezhkovskii, AM Weiss, GH TI Average volume of the domain visited by randomly injected spherical Brownian particles in d dimensions SO PHYSICAL REVIEW E LA English DT Article ID RANDOM-WALK; NUMBER; KINETICS AB In order to extend the greatly simplified Smoluchowski model for chemical reaction rates it is necessary to incorporate many-body effects. A generalization with this feature is the so-called trapping model in which random walkers move among a uniformly distributed set of traps. The solution of this model requires consideration of the distinct number of sites visited by a single n-step random walk. A recent analysis [H. Larralde et al., Phys. Rev. A 45, 1728 (1992)] has considered a generalized version of this problem by calculating the average number of distinct sites visited by N n-step random walks. A related continuum analysis is given in [A. M. Berezhkovskii, J. stat. Phys. 76.1089 (1994)]. We consider a slightly different version of the general problem by calculating the average volume of the Wiener sausage generated by Borwnian particles generated randomly in time. The analysis shows that two types of behavior are possible: one in which there is strong overlap between the Wiener sausages of the particles, and the second in which the particles are mainly independent of one another. Either one or both of these regimes occur, depending on the dimension. C1 NATL INST HLTH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP Berezhkovskii, AM (reprint author), LY KARPOV PHYS CHEM RES INST,UL OBUKHA 10,MOSCOW 103064,RUSSIA. NR 20 TC 6 Z9 6 U1 0 U2 3 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 JUL PY 1996 VL 54 IS 1 BP 92 EP 99 DI 10.1103/PhysRevE.54.92 PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA UY734 UT WOS:A1996UY73400021 ER PT J AU Bicout, DJ Field, MJ AF Bicout, DJ Field, MJ TI Relaxation dynamics in Dyson's model for the origin of metabolism SO PHYSICAL REVIEW E LA English DT Article ID RANDOM-ENERGY-MODEL; SYSTEMS; DIFFUSION AB This payer discusses some aspect of the dynamical evolution of the system described by Dyson's model for the origin of metabolism. First, the mean number of mutation events required to observe the origin of metabolism in the model is calculated. This number can span a large range depending upon the values of some critical parameters. Second, the dynamics of the relaxation to equilibrium is investigated by computing the correlation function of an on-off random function that defines the instantaneous state of the system. It was found that the dynamics of the system is well described by a double or a stretched exponential relaxation. C1 INST BIOL STRUCT,LAB DYNAM MOLEC,F-38027 GRENOBLE 01,FRANCE. RP Bicout, DJ (reprint author), NIDDKD,PHYS CHEM LAB,NIH,ROOM 136,BLDG 5,BETHESDA,MD 20892, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 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 JUL PY 1996 VL 54 IS 1 BP 726 EP 736 DI 10.1103/PhysRevE.54.726 PG 11 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA UY734 UT WOS:A1996UY73400090 ER PT J AU Zhou, HX Chen, YD AF Zhou, HX Chen, YD TI Chemically driven motility of Brownian particles SO PHYSICAL REVIEW LETTERS LA English DT Article ID FREE-ENERGY; NOISE AB A simple model is devised to show that an enzymatic Brownian particle in a static electric field can undergo directional movement when coupled with a nonequilibrium chemical reaction which the particle catalyzes, if at least one of the intermediate states of the catalytic cycle is charged. The direction of the movement depends not only on the asymmetry of the electric field, but also on the direction of the chemical reaction and the mechanism of the catalytic cycle. The Brownian particle can also move against an external load and thus do mechanical work. This study suggests that enzyme molecules could be separated based on their enzymatic activities. The formalism developed in this paper can be extended and applied to biological motors. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. RI Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 18 TC 73 Z9 75 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD JUL 1 PY 1996 VL 77 IS 1 BP 194 EP 197 DI 10.1103/PhysRevLett.77.194 PG 4 WC Physics, Multidisciplinary SC Physics GA UU475 UT WOS:A1996UU47500050 ER PT J AU Stone, EJ Osganian, SK McKinlay, SM Wu, MC Webber, LS Luepker, RV Perry, CL Parcel, GS Elder, JP AF Stone, EJ Osganian, SK McKinlay, SM Wu, MC Webber, LS Luepker, RV Perry, CL Parcel, GS Elder, JP TI Operational design and quality control in the CATCH multicenter trial SO PREVENTIVE MEDICINE LA English DT Article DE multicenter trial; quality control; children; schools ID HEART HEALTH-PROGRAM; CARDIOVASCULAR RISK-FACTORS; 6-YEAR FOLLOW-UP; SMOKING PREVENTION; DISEASE RISK; PHYSICAL-ACTIVITY; DRUG-ABUSE; EDUCATION; PROMOTION; CHILDREN AB Background. The Child and Adolescent Trial for Cardiovascular Health (CATCH) was the first multicenter school-based research study to employ the fundamentals of clinical trials including the standardized protocol and Manuals of Operation, a steering committee for study governance, a distributed data system, an extensive quality control system, and a Data and Safety Monitoring Board. Method. CATCH tested the effectiveness of changes in school lunches, physical education, smoking policy, curricula, and family activities. Ninety-six elementary schools in four states were randomized to intervention or control conditions. The baseline cohort comprised 5,106 ethnically diverse third graders followed through fifth grade. Results. The percentages of calories from fat and saturated fat were reduced significantly more in the intervention school lunches than among the controls. Significant increases in moderate to vigorous activity levels in existing physical education classes mere made as well. Changes in self-reported dietary, physical activity, and psychosocial measures were significant. There were no significant differences in the physiological measures. Measurement error was generally low for all physiologic measures except skinfolds, indicating a high level of reliability. Across all sites, the coefficients of variation for lipids, height, and weight were less than 3%, whereas for skinfolds, they were considerably higher, ranging from 6 to 8%. Intraclass correlations for Lipid studies were also uniformly high at 0.99. Interobserver agreement scores for SOFIT were greater than 90% for 9 of the 11 activities observed. Data entry error rates were low with less than five errors per 1,000 fields for all forms. Conclusions. The CATCH results provided more scientific evidence on the importance of schools in the population approach to health promotion. Many of the strategies used in this complex multicenter trial in the areas of design and analysis, measurement, training, data management, and quality control protocols might be appropriate for adoption in other studies. (C) 1996 Academic Press, Inc. C1 TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. SAN DIEGO STATE UNIV,SAN DIEGO,CA 92182. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RP Stone, EJ (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,ROCKLEDGE CTR 2,MSC 7936,6701 ROCKLEDGE DR,ROOM 8136,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL-39880, HL-39852, HL-39906] NR 68 TC 48 Z9 48 U1 3 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 384 EP 399 DI 10.1006/pmed.1996.0071 PG 16 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300002 PM 8818063 ER PT J AU Osganian, SK Ebzery, MK Montgomery, DH Nicklas, TA Evans, MK Mitchell, PD Lytle, LA Snyder, MP Stone, EJ Zive, MM Bachman, KJ Rice, R Parcel, GS AF Osganian, SK Ebzery, MK Montgomery, DH Nicklas, TA Evans, MK Mitchell, PD Lytle, LA Snyder, MP Stone, EJ Zive, MM Bachman, KJ Rice, R Parcel, GS TI Changes in the nutrient content of school lunches: Results from the CATCH eat smart food service intervention SO PREVENTIVE MEDICINE LA English DT Article DE school lunch; school food service; school-based intervention ID CARDIOVASCULAR HEALTH; PHYSICAL-ACTIVITY; FAT; CHILDREN AB Background. The Child and Adolescent Trial for Cardiovascular Health (CATCH) tested the effectiveness of a multilevel intervention aimed at promoting a healthful school environment and positive eating and physical activity behaviors in children. The CATCH Eat Smart Program targeted the school food service staff and aimed to lower the total fat, saturated fat, and sodium content of school meals. Methods. The Eat Smart intervention was conducted in 56 intervention schools over a 2 1/2-year period. Five consecutive days of school menu, recipe, and vendor product information were collected from intervention and control schools at three intervals, Fall 1991, Spring 1993, and Spring 1994, to assess the nutrient content of school menus as offered. Results. There was a significantly greater mean reduction in the percentage of calories from total fat (adjusted mean difference -4.1%; P < 0.0001) and saturated fat (adjusted mean difference -1.3%; P = 0.003) in intervention compared with control schools from baseline to follow-up. Although the sodium content of school lunches increased in both conditions, the mean increase was significantly lower in intervention schools (adjusted mean difference -89 mg;P = 0.034). There were no statistically significant differences for total amounts of cholesterol, carbohydrate, protein, dietary fiber, total sugars, calcium, iron, vitamin A value, and vitamin C. Average total calories decreased significantly; however, the mean total calories (683 kcal) for intervention schools remained above one-third of the Recommended Dietary Allowances for this age group. Conclusions. The CATCH Eat Smart intervention successfully lowered the total fat and saturated fat content of school lunches as offered, while maintaining recommended amounts of calories and essential nutrients. (C) 1996 Academic Press, Inc. C1 TUFTS UNIV NEW ENGLAND MED CTR,FRANCES STERN NUTR CTR,BOSTON,MA 02111. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77030. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70112. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. UNIV CALIF SAN DIEGO,COMMUNITY PEDIAT DIV,LA JOLLA,CA 92093. RP Osganian, SK (reprint author), NEW ENGLAND RES INST,9 GALEN ST,WATERTOWN,MA 02172, USA. FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39906, U01-HL-39880] NR 46 TC 74 Z9 75 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 400 EP 412 DI 10.1006/pmed.1996.0072 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300003 PM 8818064 ER PT J AU McKenzie, TL Nader, PR Strikmiller, PK Yang, MH Stone, EJ Perry, CL Taylor, WC Epping, JN Feldman, HA Luepker, RV Kelder, SH AF McKenzie, TL Nader, PR Strikmiller, PK Yang, MH Stone, EJ Perry, CL Taylor, WC Epping, JN Feldman, HA Luepker, RV Kelder, SH TI School physical education: Effect of the child and adolescent trial for cardiovascular health SO PREVENTIVE MEDICINE LA English DT Article DE CVD risk; children and adolescents; physical activity; CATCH; school physical education ID ELEMENTARY; FITNESS AB Background. Physical inactivity is a risk behavior for cardiovascular and other diseases. Schools can promote public health objectives by increasing physical activity among youth. Methods. The Child and Adolescent Trial for Cardiovascular Health (CATCH) was a multicenter, randomized trial to test the effectiveness of a cardiovascular health promotion program in 96 public schools in four states, A major component of CATCH was an innovative, health-related physical education (PE) program. For 2.5 years, randomly assigned schools received a standardized PE intervention, including curriculum, staff development, and follow-up. Results. Systematic analysis of 2,096 PE lessons indicated students engaged in more moderate-to-vigorous physical activity (MVPA) in intervention than in control schools (P = 0.002). MVPA during lessons in intervention schools increased from 37.4% at baseline to 51.9%, thereby meeting the established Year 2000 objective of 50%. Intervention children reported 12 more min of daily vigorous physical activity (P = 0.003) and ran 18.6 yards more than control children on a 9-min run test of fitness (P = 0.21). Conclusions: The implementation of a standardized curriculum and staff development program increased children's MVPA in existing school PF classes in four geographic and ethnically diverse communities. CATCH PE provides a tested model for improving physical education in American schools. (C) 1996 Academic Press, Inc. C1 UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70112. NEW ENGLAND RES INST,WATERTOWN,MA 02172. NHLBI,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. RP McKenzie, TL (reprint author), SAN DIEGO STATE UNIV,DEPT EXERCISE & NUTR SCI,6363 ALVARADO COURT,SUITE 250,SAN DIEGO,CA 92120, USA. FU NHLBI NIH HHS [U01HL39852, U01HL39880, U01HL39906] NR 32 TC 170 Z9 171 U1 3 U2 19 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 423 EP 431 DI 10.1006/pmed.1996.0074 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300005 PM 8818066 ER PT J AU Webber, LS Osganian, SK Feldman, HA Wu, M McKenzie, TL Nichaman, M Lytle, LA Edmundson, E Cutler, J Nader, PR Luepker, RV AF Webber, LS Osganian, SK Feldman, HA Wu, M McKenzie, TL Nichaman, M Lytle, LA Edmundson, E Cutler, J Nader, PR Luepker, RV TI Cardiovascular risk factors among children after a 21/2 year intervention - The CATCH study SO PREVENTIVE MEDICINE LA English DT Article DE risk factors; youth; school health promotion; ethnic groups; lipids; blood pressure; obesity ID BOGALUSA HEART; BLOOD-PRESSURE; HEALTH PROMOTION; BIRACIAL COMMUNITY; ADOLESCENT TRIAL; CHILDHOOD; ATHEROSCLEROSIS; TRACKING; DISEASE; ADULT AB Background. Cardiovascular risk factors and related behaviors begin during youth. Methods. As part of the Child and Adolescent Trial for Cardiovascular Health, 4,019 children from four states and representing multiple ethnic groups were measured for selected risk factors both at baseline and after 2 1/2 years of intervention. Common protocols were used for both examinations at the four sites. Results. Overall, changes in obesity, blood pressure, and serum lipids in the intervention group, compared with the control group, were not statistically significant. Total cholesterol, the primary physiologic outcome measure, decreased by 1.3 mg/dl over time in the intervention group and by 0.9 mg/dl (P > 0.05) in the control group. Different risk factor patterns for boys and girls and among three ethnic groups were noted. Conclusions. Although the school-based program effected significant institutional changes in food service and physical education class and although the children made significant changes in eating and physical activity behaviors, these did not translate to significant changes in risk factors at these ages. These behavioral changes, however, if sustained into adulthood, have the potential to influence cardiovascular risk reduction. (C) 1996 Academic Press, Inc. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. SAN DIEGO STATE UNIV,DEPT EXERCISE & NUTR STUDIES,SAN DIEGO,CA 92182. UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,CTR HLTH PROMOT RES & DEV,HOUSTON,TX 77225. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55454. UNIV TEXAS,DEPT KINESIOL & HLTH EDUC,AUSTIN,TX 78712. UNIV CALIF SAN DIEGO,COMMUNITY PEDIAT DIV,DEPT PEDIAT,LA JOLLA,CA 92093. RP Webber, LS (reprint author), TULANE UNIV,SCH PUBL HLTH & TROP MED,DEPT BIOSTAT & EPIDEMIOL,1501 CANAL ST,ROOM 1007,NEW ORLEANS,LA 70112, USA. FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39880, U01-HL-39906] NR 51 TC 71 Z9 73 U1 6 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 432 EP 441 DI 10.1006/pmed.1996.0075 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300006 PM 8818067 ER PT J AU Edmundson, E Parcel, GS Feldman, HA Elder, J Perry, CL Johnson, C Williston, BJ Stone, EJ Yang, MH Lytle, L Webber, L AF Edmundson, E Parcel, GS Feldman, HA Elder, J Perry, CL Johnson, C Williston, BJ Stone, EJ Yang, MH Lytle, L Webber, L TI The effects of the child and adolescent trial for cardiovascular health upon psychosocial determinants of diet and physical activity behavior SO PREVENTIVE MEDICINE LA English DT Article DE CVD; children; prevention; social cognitive theory ID 6-YEAR FOLLOW-UP; SMOKING PREVENTION; SELF-EFFICACY; CIGARETTE-SMOKING; DRUG-ABUSE; STRATEGIES; PROMOTION; YOUTH; INTERVENTIONS; METAANALYSIS AB Background. The Child and Adolescent Trial for Cardiovascular Health is a multisite study of a school-based intervention to reduce or prevent the development of risk factors for cardiovascular disease. The purpose of this paper is to present the evaluation results of the 3-year intervention, focusing upon the psychosocial variables conceptualized as determinants of dietary and physical activity behaviors. Methods. A total of 96 schools across four study sites (California, Louisiana, Minnesota, and Texas) were randomized to two treatment conditions: intervention and control. Pre- and postmeasurements on the health behavior questionnaire were collected from over 6,000 students. The data analyses utilized a nested design approach in which schools served as the primary unit of analysis. Repeated-measures multivariate analyses were applied to investigate effect sizes for each determinant and to explore theoretical relationships among the determinants over time. Results. The findings indicated sustained significant effects in improved knowledge, intentions, self-efficacy, usual behavior, and perceived social reinforcement for healthy food choices (P < 0.0001 for these five variables) after 3 years. Intermittent effects were observed for perceived support and self-efficacy for physical activity. No gender by determinant interaction effects were observed, and girls reported significantly greater perceived reinforcement for healthy eating than did boys. Conclusion. The CATCH program was effective in changing the psychosocial variables likely to influence a reduction in behavior for cardiovascular disease. The study is significant in that it demonstrates the viability and effectiveness of a sustained multifaceted intervention in a preadolescent population. The results point to a need for greater understanding of adolescent developmental issues and the role of community environment (particularly social support) in creating effective curricula. (C) 1996 Academic Press, Inc. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. NHLBI,BETHESDA,MD 20892. RP Edmundson, E (reprint author), UNIV TEXAS,DEPT KINESIOL,BEL 22,AUSTIN,TX 78712, USA. NR 50 TC 114 Z9 115 U1 5 U2 13 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 442 EP 454 DI 10.1006/pmed.1996.0076 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300007 PM 8812822 ER PT J AU Nader, PR Sellers, DE Johnson, CC Perry, CL Stone, EJ Cook, KC Bebchuk, J Luepker, RV AF Nader, PR Sellers, DE Johnson, CC Perry, CL Stone, EJ Cook, KC Bebchuk, J Luepker, RV TI The effect of adult participation in a school-based family intervention to improve children's diet and physical activity: The child and adolescent trial for cardiovascular health SO PREVENTIVE MEDICINE LA English DT Article DE school; family; cardiovascular disease prevention; dose ID MEXICAN-AMERICANS; RISK-FACTORS; PARENT INVOLVEMENT; CIGARETTE-SMOKING; AGGREGATION; PREVENTION; PROMOTION; BEHAVIORS; REDUCTION; PROJECT AB Background. There are strong theoretical reasons for including a family component with a school-based intervention aimed at eating, activity, and smoking behaviors, but the empirical findings to date are limited and show mixed results. The overall CATCH family intervention added only knowledge and attitudinal effects, but no additional behavioral outcomes. This study provides a dose analysis of the family component of the CATCH study by assessing the effect of the level of adult participation. Method. This secondary analysis included students who attended a CATCH family intervention school during all 3 years of the study, The extent of the adult-child interaction, the key aspect of the CATCH family intervention, was measured by the number of activity packets that an adult household member completed with the child. Multiple regression analysis was used to assess the association of adult participation with the child's knowledge, attitudes, and behaviors related to diet and physical activity. Results. Statistically significant results suggested that dose effects were found for knowledge and attitudes related to diet and physical activity. These effects were more pronounced for minority and male students. Conclusions. These results suggest that dose response of a family intervention has been shown in the acquisition of positive knowledge and attitudes toward health habit changes. The methodology of dose response can be applied to other health promotion projects. (C) 1996 Academic Press, Inc. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. NHLBI,BETHESDA,MD 20892. UNIV TEXAS,SCH PUBL HLTH,HOUSTON,TX 77225. RP Nader, PR (reprint author), UNIV CALIF SAN DIEGO,DEPT PEDIAT,9500 GILMAN DR,DEPT 0927,LA JOLLA,CA 92093, USA. FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39906, U01-HL-39880] NR 34 TC 86 Z9 88 U1 1 U2 11 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 455 EP 464 DI 10.1006/pmed.1996.0077 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300008 PM 8818068 ER PT J AU Lytle, LA Stone, EJ Nichaman, MZ Perry, CL Montgomery, DH Nicklas, TA Zive, MM Mitchell, P Dwyer, JT Ebzery, MK Evans, MA Galati, TP AF Lytle, LA Stone, EJ Nichaman, MZ Perry, CL Montgomery, DH Nicklas, TA Zive, MM Mitchell, P Dwyer, JT Ebzery, MK Evans, MA Galati, TP TI Changes in nutrient intakes of elementary school children following a school-based intervention: Results from the CATCH study SO PREVENTIVE MEDICINE LA English DT Article DE nutrient intakes; school health promotion; children ID CARDIOVASCULAR HEALTH CATCH; PHYSICAL-ACTIVITY; ADOLESCENT TRIAL; RISK REDUCTION; UNITED-STATES; DISEASE; DIET; PREVENTION; PROMOTION; TRACKING AB Background. Twenty-four-hour recalls were used to assess the change in nutrient intake among elementary-age school children exposed to the Child and Adolescent Trial for Cardiovascular Health (CATCH). The purpose of this paper is to compare changes in nutrient intakes between treatment groups, sexes, ethnic groups, and the four CATCH sites. Methods. Twenty-four-hour recalls were administered to a subsample of the CATCH cohort at baseline in third grade and following the intervention in fifth grade (n = 1,182). Changes in nutrient levels for total energy, dietary cholesterol, and dietary fiber and changes in the proportion of energy from fat, protein, carbohydrate, and fatty acids were studied looking at differences by treatment group, sex, ethnicity, and site. Mixed-model analysis of variance was used to examine the change in nutrient intake, defined as intake at follow-up minus intake at baseline. Results. Students in the intervention schools showed statistically significant differences in the changes in total energy and proportion of energy from total fat, saturated fat, protein, and monounsaturated fat compared with students in the control group. Students in the intervention group decreased their total fat intake from 32.7% of energy to 30.3% of energy and saturated fat from 12.8% of energy to 11.4% of energy. There were no significant differences in intervention effects by ethnic group, sex, or site. Differences in nutrient change between the school-only and the school-plus-family intervention groups were nonsignificant. Conclusion. The results show that a school-based intervention can positively influence children's intakes of total fat and saturated fat, suggesting that population-based approaches for reducing cardiovascular risk factors in children are feasible and effective. The results are also important in showing that the intervention was effective in Caucasian, African-American, and Hispanic students, in boys and girls, and across four regions of the United States. (C) 1996 Academic Press, Inc. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77030. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70112. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. NEW ENGLAND RES INST,WATERTOWN,MA 02172. TUFTS UNIV NEW ENGLAND MED CTR,FRANCIS STERN NUTR CTR,BOSTON,MA 02111. RP Lytle, LA (reprint author), UNIV MINNESOTA,DIV EPIDEMIOL,SCH PUBL HLTH,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [U01 HL 39852, U01 HL 39870, U01 HL 39927] NR 67 TC 73 Z9 75 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 465 EP 477 DI 10.1006/pmed.1996.0078 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300009 PM 8818069 ER PT J AU Nicklas, TA Dwyer, J Mitchell, P Zive, M Montgomery, D Lytle, L Cutler, J Evans, M Cunningham, A Bachman, K Nichaman, M Snyder, P AF Nicklas, TA Dwyer, J Mitchell, P Zive, M Montgomery, D Lytle, L Cutler, J Evans, M Cunningham, A Bachman, K Nichaman, M Snyder, P TI Impact of fat reduction on micronutrient density of children's diets: The CATCH study SO PREVENTIVE MEDICINE LA English DT Article DE children's diets; nutrition; micronutrients; fat reduction ID CARDIOVASCULAR HEALTH CATCH; SCHOOL-BASED INTERVENTION; ADOLESCENT TRIAL; GUIDELINES; PROMOTION; DISEASE AB Background. The purpose of this study was to examine the impact of fat reduction on vitamin and mineral density in the diets of groups of children who participated in the CATCH school-based intervention study for 2 1/2 years. Methods. Twenty-four-hour dietary recalls were collected on 1,182 children residing in four states and with diverse ethnic backgrounds, at baseline when they mere in third grade and again at follow-up when they were in fifth grade. Results. With a 2.4% reduction in total fat intake from baseline levels in the intervention group, mean changes in vitamin and mineral intakes per 1,000 kcal of this group were small yet significant compared with the control group. As mean fat intake decreased, the nutrient density of most vitamins and minerals increased; the sole exceptions were vitamin E and sodium. Mean intake of all vitamins and minerals studied exceeded 2/3 of the RDA at both baseline and followup for both the intervention and the control groups. No significant differences were noted between treatment groups for the percentages of children meeting 2/3 or more of the RDA at both baseline and follow-up periods. Conclusions. CATCH was successful in maintaining mean vitamin and mineral intakes of intervention group children when total dietary fat was reduced. (C) 1996 Academic Press, Inc. C1 TUFTS UNIV NEW ENGLAND MED CTR,FRANCES STERN NUTR CTR,BOSTON,MA 02111. NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV CALIF SAN DIEGO,DEPT PEDIAT,COMMUNITY PEDIAT DIV,LA JOLLA,CA 92093. UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,CTR HLTH PROMOT RES & DEV,HOUSTON,TX 77225. UNIV MINNESOTA,DIV EPIDEMIOL,SCH PUBL HLTH,MINNEAPOLIS,MN 55454. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,ROCKLEDGE CTR 2,BETHESDA,MD 20892. RP Nicklas, TA (reprint author), TULANE UNIV,SCH PUBL HLTH & TROP MED,TULANE CTR CARDIOVASC HLTH,1501 CANAL ST,12TH FLOOR,NEW ORLEANS,LA 70112, USA. OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39880, U01-HL-39906] NR 36 TC 33 Z9 33 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 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 478 EP 485 DI 10.1006/pmed.1996.0079 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300010 PM 8818070 ER PT J AU Elder, JP Perry, CL Stone, EJ Johnson, CC Yang, MH Edmundson, EW Smyth, MH Galati, T Feldman, H Cribb, P Parcel, GS AF Elder, JP Perry, CL Stone, EJ Johnson, CC Yang, MH Edmundson, EW Smyth, MH Galati, T Feldman, H Cribb, P Parcel, GS TI Tobacco use measurement, prediction, and intervention in elementary schools in four states: The CATCH study SO PREVENTIVE MEDICINE LA English DT Article DE school tobacco policy; smoking prevention ID SMOKING PREVENTION; DRUG-USE; ADOLESCENT; ACQUISITION; TRIAL AB Background. The Child and Adolescent Trial for Cardiovascular Health (CATCH) is a multistate field trial examining the effects of school environment, classroom curricula, and family intervention components in promoting the cardiovascular health of elementary school students. The purpose of this paper is to describe the CATCH tobacco use intervention and measurement, including the adoption of tobacco-free school policies. Methods. In this study, changes in school tobacco use policies and smoking experimentation among students were assessed. Smoking experimentation was measured in all CATCH schools when the students were in their fifth-grade year. A total of 6,527 subjects in 96 schools in California, Louisiana, Minnesota, and Texas answered questions about behaviors and potential correlates of smoking as part of the CATCH health behavior questionnaire in Spring 1994. School tobacco use policy, an important complement to classroom- and home-based prevention efforts, was promoted as part of the CATCH intervention. The degree to which such policy was implemented was measured using surveys of school officials. Results. At the end of fifth grade, only 4.8% of the subjects indicated that they had experimented with tobacco. School intervention condition was not a factor in the prediction of experimentation. Those whose best friend or sibling smoked, or who had ready access to cigarettes in the home, were more likely to have experimented with smoking. In the 3 years of the study, the percentages of tobacco-free schools went up from 49.7 to 76.8%. Though differences in the rate of policy adoption could not be directly attributed to the CATCH intervention, the implementation of the tobacco-free schools' policies did vary substantially from state to state. Minnesota and Texas, with stronger state laws supporting local policy, had nearly completely smoke-free schools. In spite of a statewide tobacco control initiative, California was slower to implement school policies. Louisiana, which allows local decision making regarding smoking policy, had the most difficulty establishing a policy for all districts. Conclusion. Future studies should examine the impact of parallel policy interventions that are ongoing at both school and state levels. Tobacco-free policies appear to be a crucial part of school-based interventions and must be tailored to political and regional factors affecting a given school district. (C) 1996 Academic Press, Inc. C1 UNIV MINNESOTA, SCH PUBL HLTH, DIV EPIDEMIOL, MINNEAPOLIS, MN 55454 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, ROCKLEDGE CTR 2, BETHESDA, MD 20892 USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. TULANE UNIV, SCH PUBL HLTH & TROP MED, NEW ORLEANS, LA 70112 USA. UNIV TEXAS, DEPT KINESIOL & HLTH EDUC, AUSTIN, TX 78712 USA. UNIV TEXAS, HLTH SCI CTR, CTR HLTH PROMOT RES & DEV, SCH PUBL HLTH, HOUSTON, TX 77225 USA. UNIV CALIF SAN DIEGO, SCH MED, LA JOLLA, CA 92093 USA. RP Elder, JP (reprint author), SAN DIEGO STATE UNIV, GRAD SCH PUBL HLTH, DIV HLTH PROMOT, 5500 CAMPANILE DR, SAN DIEGO, CA 92182 USA. FU NHLBI NIH HHS [U01-HL-39906, U01-HL-39852, U01-HL-39880] NR 33 TC 49 Z9 53 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 0091-7435 J9 PREV MED JI Prev. Med. PD JUL-AUG PY 1996 VL 25 IS 4 BP 486 EP 494 DI 10.1006/pmed.1996.0080 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VB783 UT WOS:A1996VB78300011 PM 8812826 ER PT J AU Aldroubi, A AF Aldroubi, A TI Oblique projections in atomic spaces SO PROCEEDINGS OF THE AMERICAN MATHEMATICAL SOCIETY LA English DT Article DE oblique projection; biorthogonal multiwavelet; multiwavelets; unitary operators; Riese basis ID MULTIRESOLUTION; APPROXIMATIONS; SUBSPACES; WAVELETS; BASES AB Let H be a Hilbert space, O a unitary operator on H, and {phi(i)}(i=1,...,tau). tau vectors in H. We construct an atomic subspace U subset of H: [GRAPHICS] We give the necessary and sufficient conditions for U to be a well-defined, closed subspace of H with {O-k phi(i)}(i=1,...,tau, k is an element of Z) consider the oblique projection P-U perpendicular to V on the space U(O,{phi(U)(i)}(i=1,...,tau)) in a direction orthogonal to V(O, {phi(U)i}(i=1,...,tau)). We give the necessary and sufficient conditions on O, {phi(U)(i)}(i=1,...,tau), and {phi(V)(i)}(i=1,...,tau) for P-U perpendicular to V to be well defined. The results can be used to construct biorthogonal multiwavelets in various spaces. They can also be used to generalize the Shannon-Whittaker theory on uniform sampling. RP Aldroubi, A (reprint author), NIH, BEIP, BLDG 13-3N17, 13 S DR MSC 5766, BETHESDA, MD 20892 USA. RI Aldroubi, Akram/J-7186-2012 NR 20 TC 53 Z9 54 U1 0 U2 0 PU AMER MATHEMATICAL SOC PI PROVIDENCE PA 201 CHARLES ST, PROVIDENCE, RI 02940-2213 USA SN 0002-9939 J9 P AM MATH SOC JI Proc. Amer. Math. Soc. PD JUL PY 1996 VL 124 IS 7 BP 2051 EP 2060 DI 10.1090/S0002-9939-96-03255-8 PG 10 WC Mathematics, Applied; Mathematics SC Mathematics GA UX878 UT WOS:A1996UX87800013 ER PT J AU Bonifacino, JS Marks, MS Ohno, H Kirchhausen, T AF Bonifacino, JS Marks, MS Ohno, H Kirchhausen, T TI Mechanisms of signal-mediated protein sorting in the endocytic and secretory pathways SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article ID TRANS-GOLGI NETWORK; MANNOSE 6-PHOSPHATE RECEPTOR; FACTOR-II RECEPTOR; DI-LEUCINE MOTIF; LYSOSOMAL MEMBRANE-GLYCOPROTEINS; GROWTH-FACTOR RECEPTOR; CYTOPLASMIC DOMAIN; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; COATED PITS AB The ability to sort proteins to different intracellular compartments is an essential property of all cells. Many diseases are caused by a failure of certain proteins to be sorted properly in the endocytic and secretory pathways. In addition, various intracellular pathogens use their hosts' protein-sorting machinery at different stages of their life cycles. These facts underscore the importance of understanding the mechanisms of protein sorting at a molecular level. In this article, we review recent advances in the identification of signals that direct proteins to their correct intracellular locations and of the recognition molecules that bind to the signals. The implications of these findings for the trafficking of various proteins are discussed. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA. RP Bonifacino, JS (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NATL INST HLTH,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Marks, Michael/0000-0001-7435-7262; Bonifacino, Juan S./0000-0002-5673-6370 NR 76 TC 39 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JUL PY 1996 VL 108 IS 4 BP 285 EP 295 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VD968 UT WOS:A1996VD96800001 PM 8863342 ER PT J AU Karl, M Lamberts, SWJ Koper, JW Katz, DA Huizenga, NE Kino, T Haddad, BR Hughes, MR Chrousos, GP AF Karl, M Lamberts, SWJ Koper, JW Katz, DA Huizenga, NE Kino, T Haddad, BR Hughes, MR Chrousos, GP TI Cushing's disease preceded by generalized glucocorticoid resistance: Clinical consequences of a novel, dominant-negative glucocorticoid receptor mutation SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE pituitary gland; corticotroph adenoma ID PRIMARY CORTISOL RESISTANCE; HORMONE RECEPTOR; THYROID-HORMONE; BINDING DOMAIN; ACID; EXPRESSION; SEQUENCE; CDNA; GENE; ADENOMAS AB Generalized glucocorticoid resistance is associated with chronic hyperactivation of the hypothalamic-pituitary-adrenal axis, compensating for impaired glucocorticoid receptor function. We report a unique patient with sporadic generalized glucocorticoid resistance who, at age 33, presented with infertility and hypertension and, at a disease, Leukocyte-binding studies revealed normal affinity of the glucocorticoid receptor but a reduction of binding sites by 50%. [H-3]thymidine incorporation by this patient's lymphocytes Miss not suppressible by dexamethasone. tie had a novel heterozygous missense mutation in the glucocorticoid receptor gene (isoleucine 559 to asparagine 559). The mutant receptor exhibited a strong dominant-negative effect on the ability of the wild-type receptor to induce gene transcription in vitro. The mutation was present in all of the patient's cultured lymphoblasts and fibroblasts as well as in 50% of his sperm. as demon strated by single-cell polymerase chain reaction; it was not present in his parents and seven siblings. This novel mutation was thus both de novo and present in the germ line. Immunohistochemical staining of this patient's pituitary corticotropinoma revealed accumulation of p53 protein, indicating the presence of a putative somatic oncogenic mutation in the p53 gene in the tumor cells. Investigation of the lymphoblast and skin fibroblast cul tures for p53 abnormalities did not show any aberration. Thus, a novel de no iio germ line mutation of the glucocorticoid receptor with strong dominant-negative activity caused severe sporadic generalized glucocorticoid resistance, which preceded corticotroph adenoma formation. The latter probably was due to the combined effects of chronic corticotroph hyperstimulation, decreased glucocorticoid negative feedback, and at least one subsequent somatic defect in the control of the cell cycle. C1 ERASMUS UNIV ROTTERDAM, HOSP DIJKZIGT, DEPT MED, NL-3015 GD ROTTERDAM, NETHERLANDS. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NINCDS, BETHESDA, MD 20892 USA. NATL INST HLTH, NATL CTR HUMAN GENOME RES, DIAGNOST DEV BRANCH, BETHESDA, MD USA. RP Karl, M (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NATL INST HLTH,BLDG 10, RM 10N262,MSC 1862, 10 CTR DR, BETHESDA, MD 20892 USA. NR 40 TC 122 Z9 127 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JUL PY 1996 VL 108 IS 4 BP 296 EP 307 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VD968 UT WOS:A1996VD96800002 PM 8863343 ER PT J AU Alexandrov, NN Fischer, D AF Alexandrov, NN Fischer, D TI Analysis of topological and nontopological structural similarities in the PDB: New examples with old structures SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE classification of protein structures; method for structural comparison; porin; bacteriochlorophyll a protein; sequence-structure relationship; WWW ID PROTEIN FOLD FAMILIES; NONHOMOLOGOUS PROTEINS; SPATIAL ARRANGEMENTS; GLOBULAR-PROTEINS; CLASSIFICATION; ALIGNMENT; RESOLUTION; HOLOENZYME; DATABASE AB We have developed a new method and program, SARF2, for fast comparison of protein structures, which can detect topological as well as nontopological similarities, The method searches for large ensembles of secondary structure elements, which are mutually compatible in two proteins. These ensembles consist of small fragments of C-alpha-trace, similarly arranged in three-dimensional space in two proteins, but not necessarily equally-ordered along the polypeptide chains. The program SARF2 is available for everyone through the World-Wide Web (WWW), We have performed an exhaustive pairwise comparison of all the entries from a recent issue of the Protein Data Bank (PDB) and report here on the results of an automated hierarchical cluster analysis, In addition, we report on several new cases of significant structural resemblance between proteins, To this end, a new definition of the significance of structural similarity is introduced, which effectively distinguishes the biologically meaningful equivalences from those occurring by chance. Analyzing the distribution of sequence similarity in significant structural matches, we show that sequence similarity as low as 20% in structurally-prealigned proteins can be a strong indication for the biological relevance of structural similarity. (C) 1996 Wiley-Liss, Inc. C1 NCI,MATH BIOL LAB,NIH,FREDERICK,MD 21701. NR 32 TC 76 Z9 80 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD JUL PY 1996 VL 25 IS 3 BP 354 EP 365 DI 10.1002/(SICI)1097-0134(199607)25:3<354::AID-PROT7>3.3.CO;2-W PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UZ837 UT WOS:A1996UZ83700008 PM 8844870 ER PT J AU Malhotra, AK Pickar, D AF Malhotra, AK Pickar, D TI Biologic predictors of clozapine response in schizophrenia SO PSYCHIATRIC ANNALS LA English DT Article ID PLASMA HOMOVANILLIC-ACID; ANTIPSYCHOTIC-DRUGS; FLUPHENAZINE; NOREPINEPHRINE; METABOLITES; EFFICACY; GENE RP Malhotra, AK (reprint author), NIMH,ETB,10 CTR DR,BLDG 10,RM 4N212,BETHESDA,MD 20892, USA. NR 35 TC 4 Z9 4 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 JUL PY 1996 VL 26 IS 7 BP 390 EP 394 PG 5 WC Psychiatry SC Psychiatry GA UX642 UT WOS:A1996UX64200004 ER PT J AU Torrey, EF AF Torrey, EF TI Medicaid block grants could be a step forward SO PSYCHIATRIC SERVICES LA English DT Editorial Material RP Torrey, EF (reprint author), NIMH,CTR NEUROSCI,ST ELIZABETHS HOSP,WASHINGTON,DC 20032, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JUL PY 1996 VL 47 IS 7 BP 679 EP 679 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA UV458 UT WOS:A1996UV45800001 PM 8807678 ER PT J AU Hampel, H Berger, C Muller, N AF Hampel, H Berger, C Muller, N TI A case of Ganser's state presenting as a dementia syndrome SO PSYCHOPATHOLOGY LA English DT Article ID DISORDER AB We report an atypical case of Ganser's syndrome in a 54-year-old male patient, The following symptoms which include approximate answers, perceptual disturbances and dissociative mechanisms were observed over 7 years, improved during hospitalization, but reappeared just before the patient's discharge. The extremely long presence and bizarre manifestation of symptoms, the course of the disorder and the patient's premorbid high intelligence level point to an unusual presentation of this case. Following the concept of hysteria and dissociation, we discuss its diagnosis within the scope of the DSM-III-R. DSM-IV and ICD-10 classification of Dissociative Disorders. Problems in the differential diagnosis which result from an increasing awareness of Dissociative Disorders are outlined. C1 UNIV MUNICH,DEPT PSYCHIAT,D-8000 MUNICH,GERMANY. RP Hampel, H (reprint author), NIA,NIH,NEUROSCI LAB,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Hampel, Harald/0000-0003-0894-8982 NR 17 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PD JUL-AUG PY 1996 VL 29 IS 4 BP 236 EP 241 PG 6 WC Psychiatry SC Psychiatry GA VC156 UT WOS:A1996VC15600007 PM 8865355 ER PT J AU Johanson, CE Evans, S Henningfield, J AF Johanson, CE Evans, S Henningfield, J TI The discriminative stimulus effects of tripelennamine in humans SO PSYCHOPHARMACOLOGY LA English DT Article DE antihistamines; tripelennamine; drug discrimination; subjective effects; humans ID DRUG DISCRIMINATION; D-AMPHETAMINE; ANTIHISTAMINE; PHENMETRAZINE; DIAZEPAM; TRENDS AB Twenty volunteers were trained to discriminate between 75 mg tripelennamine (TP) and placebo, During the first four sessions, the drugs were identified prior to ingestion by letter code, During the next is sessions, the procedure was the same except the capsules were not identified. At the end of the 3-h session, participants indicated which capsule they believed they received using the letter codes, When correct, they received a monetary bonus. If they were correct on five sessions, they entered the third phase which had tell additional training and 12 test sessions. During tests, participants received capsules that contained other drugs, including diphenhydramine (50 and 75 mg), chlorpheniramine (4 and 6 mg), diazepam (5 and 10 mg), d-amphetamine (5 and 10 mg), as well as tripelennamine (25, 50 and 75 mg) and placebo. Thirteen participants learned the discrimination and nine entered the third phase, Except for placebo, most participants identified the test compounds as TP and labeled them as sedatives. TP produced significant changes on several subjective and physiological measures. The test compounds produced varied effects which were neither clearly dose-related nor related to the identification as TP or placebo, These results indicate that tripelennamine call function as a discriminative stimulus, but with little evidence of pharmacological specificity. C1 COLUMBIA UNIV,SCH MED,NEW YORK,NY 10032. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD 21224. RP Johanson, CE (reprint author), WAYNE STATE UNIV,DEPT PSYCHIAT & BEHAV NEUROSCI,2761 E JEFFERSON,DETROIT,MI 48207, USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1996 VL 126 IS 2 BP 140 EP 146 DI 10.1007/BF02246349 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VA069 UT WOS:A1996VA06900007 PM 8856833 ER PT J AU Brownley, KA Light, KC Anderson, NB AF Brownley, KA Light, KC Anderson, NB TI Social support and hostility interact to influence clinic, work, and home blood pressure in Black and White men and women SO PSYCHOPHYSIOLOGY LA English DT Article DE hostility; social support; ambulatory blood pressure; anger; gender; ethnicity ID CORONARY-ARTERY DISEASE; CARDIOVASCULAR REACTIVITY; MYOCARDIAL-INFARCTION; ANGIOGRAPHIC FINDINGS; HEART-DISEASE; A BEHAVIOR; ANGER-IN; STRESS; COMPONENTS; HYPERTENSION AB The effects of hostility and social support on clinic, work, and home systolic (SBP) and diastolic (DBP) blood pressures were evaluated in 129 healthy adults. High hostility was related to higher SBP and DBP in Whites; low hostility was related to higher SBP and DBP in Blacks. These relationships were significant for men at home and at work and for women at screening. The relationship between low hostility and higher BP in Blacks was largely due to Black men who reported low hostility plus high anger-in (suggesting suppressed hostility). In contrast, high hostile Black men with high tangible support tended to exhibit lower BP than all other Black men. In White women, high belonging support was related to lower BP, independent of hostility, and low tangible support plus high hostility was related to higher clinic BP. In high hostile subjects, regardless of ethnicity or gender, high appraisal support was related to lower overall BP. These data suggest that the adverse BP effects of hostility and the beneficial effects of social support interact in a complex manner, reflecting contextual, ethnic, and gender specificities. C1 UNIV N CAROLINA, DEPT PSYCHIAT, CHAPEL HILL, NC 27599 USA. NIH, OFF BEHAV & SOCIAL SCI RES, BETHESDA, MD 20892 USA. RP Brownley, KA (reprint author), UNIV N CAROLINA, DEPT PSYCHOL, CB 7175, MED RES BLDG A, CHAPEL HILL, NC 27599 USA. FU NCRR NIH HHS [RR00046]; NHLBI NIH HHS [R01 HL31533]; NIMH NIH HHS [MH09885] NR 70 TC 25 Z9 25 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JUL PY 1996 VL 33 IS 4 BP 434 EP 445 DI 10.1111/j.1469-8986.1996.tb01069.x PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA UU133 UT WOS:A1996UU13300013 PM 8753944 ER PT J AU Knox, SS Jacobs, DR Chesney, MA Raczynski, J McCreath, H AF Knox, SS Jacobs, DR Chesney, MA Raczynski, J McCreath, H TI Psychosocial factors and plasma lipids in black and white young adults: The coronary artery risk development in young adults study data SO PSYCHOSOMATIC MEDICINE LA English DT Article DE lipids; health behaviors; hostility; social support; Type A; education ID DENSITY-LIPOPROTEIN CHOLESTEROL; SERUM TOTAL CHOLESTEROL; UNITED-STATES ADULTS; A BEHAVIOR; HEART-DISEASE; SOCIAL SUPPORT; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; MORTALITY; HOSTILITY AB These analyses examined the relationship between fasting plasma lipids and several psychosocial factors in a healthy cohort of 5115 black and white men and women between the ages of 18 and 30. Primary analyses were performed within race/gender subgroups and were supplemented with analyses examining consistency of associations across these groups. After controlling for age, high density lipoprotein (HDL) decreased, triglycerides increased, low density lipoprotein (LDL) increased, and the total cholesterol/HDL cholesterol ratio increased with increasing level of education in black men. This pattern is, in general, opposite to that found in other groups, particularly white women, whose lipid profile was found to be less atherogenic the higher the education. These associations were strongly confounded with health behaviors. There was also a positive association between hostility and triglycerides in women but not in men. No significant association with any plasma lipid for either race or gender was found for Type A behavior, social support, of life events. Despite a narrow plasma lipid range in these young adults, these data support the conclusion that increasing education is associated with a less atherogenic plasma lipid profile, except in black men, for whom education is associated with a less favorable plasma lipid profile. Among other psychosocial factors, the only consistent finding was an inverse association between hostility and triglycerides in women. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV CALIF SAN FRANCISCO,DIV GEN INTERNAL MED,SAN FRANCISCO,CA 94143. UNIV ALABAMA,SCH MED,DIV PREVENT MED,BIRMINGHAM,AL. RP Knox, SS (reprint author), NHLBI,BEHAV MED SCI RES GRP,II ROCKLEDGE CTR,RM 8120,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48049, N01-HC-48048] NR 57 TC 26 Z9 26 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 1996 VL 58 IS 4 BP 365 EP 373 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA UY248 UT WOS:A1996UY24800010 PM 8827799 ER PT J AU Vecchioli, D AF Vecchioli, D TI Epidemiologic maps of Washington DC, 1878-1909 SO PUBLIC HEALTH REPORTS LA English DT Article AB IN ORDER TO demonstrate the dire effects that contagious epidemic diseases were having on the population of Washington DC, Public Health Officers of the District of Columbia used epidemiological maps in their annual reports to city commissioners from 1878 until 1909. These maps charted information graphically that was included as statistical tables elsewhere in the reports. Their evolution occurred during a period when the Health Officers themselves were coming to grips with the causes of diseases that included diphtheria, scarlet fever typhoid and malarial fevers, smallpox, consumption (tuberculosis), and diarrheal diseases. The maps may have encouraged laws that were passed during this period which required. Washington DC physicians to report cases and deaths from these diseases. RP Vecchioli, D (reprint author), NIH,NATL LIB MED,HIST MED DIV,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1996 VL 111 IS 4 BP 314 EP 319 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ414 UT WOS:A1996UZ41400015 PM 8711096 ER PT J AU Land, CE Saku, T Hayashi, Y Takahara, O Matsuura, H Tokuoka, S Tokunaga, M Mabuchi, K AF Land, CE Saku, T Hayashi, Y Takahara, O Matsuura, H Tokuoka, S Tokunaga, M Mabuchi, K TI Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk SO RADIATION RESEARCH LA English DT Article ID EPIDEMIOLOGIC OBSERVATIONS; CHILDHOOD IRRADIATION; CANCER; HIROSHIMA; NEOPLASMS; HEAD; JAPAN; DS86 AB A wide-ranging search for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR(1Sv), with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7) for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR(1Sv) = 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin's tumor [12 cases, RR(1Sv) = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR(1Sv) = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin's tumor [RR(1Sv) = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study. (C) 1996 by Radiation Research Society C1 NAGASAKI UNIV,SCH DENT,DEPT ORAL PATHOL,NAGASAKI 852,JAPAN. HIROSHIMA ASA CITIZENS HOSP,DEPT CLIN LABS,PATHOL SECT,HIROSHIMA,JAPAN. RED CROSS NAGASAKI A BOMB HOSP,DEPT CLIN LABS 2,NAGASAKI,JAPAN. HIROSHIMA CITIZENS HOSP,DEPT PATHOL,HIROSHIMA,JAPAN. KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA,JAPAN. RP Land, CE (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,ROCKVILLE,MD 20892, USA. NR 34 TC 61 Z9 61 U1 1 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1996 VL 146 IS 1 BP 28 EP 36 DI 10.2307/3579392 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA UV096 UT WOS:A1996UV09600002 PM 8677295 ER PT J AU Ungerleider, LG AF Ungerleider, LG TI Memory's mazes SO RECHERCHE LA French DT Article ID INFERIOR TEMPORAL CORTEX; ACTIVATION; NEURONS; PRIMATE RP Ungerleider, LG (reprint author), NIMH,NIH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892, USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SOC ED SCIENTIFIQUES PI PARIS 06 PA 57 RUE DE SEINE, 75280 PARIS 06, FRANCE SN 0029-5671 J9 RECHERCHE JI Recherche PD JUL-AUG PY 1996 IS 289 BP 70 EP 74 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UV094 UT WOS:A1996UV09400030 ER PT J AU Muller, DC Elahi, D Tobin, JD Andres, R AF Muller, DC Elahi, D Tobin, JD Andres, R TI The effect of age on insulin resistance and secretion: A review SO SEMINARS IN NEPHROLOGY LA English DT Article ID MUSCLE BLOOD-FLOW; DEPENDENT DIABETES-MELLITUS; MEDIATED GLUCOSE-UPTAKE; SYMPATHETIC NEURAL ACTIVATION; BODY-FAT DISTRIBUTION; SKELETAL-MUSCLE; C-PEPTIDE; CARBOHYDRATE-METABOLISM; HEPATIC EXTRACTION; ELDERLY SUBJECTS C1 UNIV MARYLAND, SCH MED, DEPT MED, DIV GERONTOL, BALTIMORE, MD 21201 USA. RP Muller, DC (reprint author), NIA, LAB CLIN PHYSIOL, GERONTOL RES CTR, NIH, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 79 TC 61 Z9 61 U1 3 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 EI 1558-4488 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JUL PY 1996 VL 16 IS 4 BP 289 EP 298 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA UW902 UT WOS:A1996UW90200004 PM 8829267 ER PT J AU Johnson, BE Kelley, MJ AF Johnson, BE Kelley, MJ TI Biology and molecular genetics of lung cancer SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID EPIDERMAL GROWTH-FACTOR; HUMAN SMALL-CELL; RETINOBLASTOMA SUSCEPTIBILITY GENE; GASTRIN-RELEASING PEPTIDE; TUMOR-SUPPRESSOR LOCUS; BOMBESIN-LIKE PEPTIDES; FACTOR-RECEPTOR; FACTOR-ALPHA; CARCINOMA-CELLS; SHORT ARM C1 NCI,NAVY MED ONCOL BRANCH,LUNG CANC BIOL SECT,BETHESDA,MD. OI Kelley, Michael/0000-0001-9523-6080 NR 139 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PD JUL PY 1996 VL 17 IS 4 BP 299 EP 308 DI 10.1055/s-2007-1009902 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UX953 UT WOS:A1996UX95300004 ER PT J AU Burk, RD Kelly, P Feldman, J Bromberg, J Vermund, SH Dehovitz, JA Landesman, SH AF Burk, RD Kelly, P Feldman, J Bromberg, J Vermund, SH Dehovitz, JA Landesman, SH TI Declining prevalence of cervicovaginal human papillomavirus infection with age is independent of other risk factors SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID GENITAL HUMAN PAPILLOMAVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOLOGICALLY NORMAL WOMEN; POLYMERASE CHAIN-REACTION; CERVICAL-CANCER; SEXUAL-BEHAVIOR; NEW-MEXICO; HPV; DETERMINANTS; NEOPLASIA AB Background and Objectives: Human papillomavirus (HPV) infection of the female genital tract is the most common sexually transmitted disease, Although the prevalence of HPV in women without detectable cervical disease has been shown to decline with increasing age, the relationship to sexual behavior has not been investigated. Goal: To identify risk factors for, and associated with the age-dependent decline in, genital HPV infection in women, Study Design: The prevalence of HPV was determined in a cohort of 439 sexually active inner-city women between the ages of 18 and 50 years recruited in Brooklyn, New York, Cervicovaginal cells were collected by lavage, and HPV was detected by low-stringent Southern blot hybridization, Results: The prevalence of HPV infection ranged from 36% in women younger than 25 years of age to 2.8% in women 45 years or older, Logistic regression analysis identified an increased risk for cervical HPV infection to be independently associated with number of sex partners in the past year (odds ratio [OR], 1.04 per yearly increase in age; 95% confidence interval [CI], 1.00 to 1.08), younger age (OR, 0.92 per year increase in age; 95% CI, 0.88 to 0.95), and not living with partner (OR, 2.28; 95% CI, 1.40 to 4.22), Conclusions: The lower prevalence of HPV infection in older women compared to younger women was found to be independent of sexual behavior, These results suggest that a biologic effect, such as HPV immunity acquired over time and with multiple exposures, may mediate the inverse relationship between age and HPV prevalence. C1 ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY. ALBERT EINSTEIN COLL MED,DEPT OBSTET & GYNECOL,BRONX,NY. SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT PREVENT MED & COMMUNITY HLTH,BROOKLYN,NY 11203. UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. RP Burk, RD (reprint author), ALBERT EINSTEIN COLL MED,DEPT PEDIAT,ULLMANN BLDG,ROOM 625,1300 MORRIS PK AVE,BRONX,NY 10461, USA. OI Vermund, Sten/0000-0001-7289-8698 NR 46 TC 148 Z9 153 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL-AUG PY 1996 VL 23 IS 4 BP 333 EP 341 DI 10.1097/00007435-199607000-00013 PG 9 WC Infectious Diseases SC Infectious Diseases GA UY688 UT WOS:A1996UY68800013 PM 8836027 ER PT J AU Ulevitch, RJ Dunn, DL Fink, MP Taylor, CE AF Ulevitch, RJ Dunn, DL Fink, MP Taylor, CE TI Endotoxin-related intracellular pathways: Implications for therapeutic intervention SO SHOCK LA English DT Editorial Material C1 UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. BETH ISRAEL HOSP,DIV TRAUMA & SURG CRIT CARE,BOSTON,MA 02215. NIAID,DIV MICROBIOL & INFECT DIS,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. NR 0 TC 8 Z9 8 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9, AUGUSTA, GA 30901 SN 1073-2322 J9 SHOCK JI Shock PD JUL PY 1996 VL 6 IS 1 BP 1 EP 2 DI 10.1097/00024382-199607000-00001 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA UX765 UT WOS:A1996UX76500001 PM 8828075 ER PT J AU Deutch, AY Lewis, DA Whitehead, RE Elsworth, JD Iadarola, MJ Redmond, DE Roth, RH AF Deutch, AY Lewis, DA Whitehead, RE Elsworth, JD Iadarola, MJ Redmond, DE Roth, RH TI Effects of D-2 dopamine receptor antagonists on fos protein expression in the striatal complex and entorhinal cortex of the nonhuman primate SO SYNAPSE LA English DT Article DE antipsychotic drugs; caudate nucleus; extrapyramidal side effects; immediate-early gene; nucleus accumbens; schizophrenia ID ATYPICAL ANTIPSYCHOTIC-DRUGS; C-FOS; CEREBRAL-CORTEX; BASAL GANGLIA; RAT STRIATUM; HUMAN BRAIN; SCHIZOPHRENIA; BINDING; MONKEY; ORGANIZATION AB Recent studies have reported that acute administration of dopamine D-2 receptor antagonists increases expression of the immediate early gene c-fos in the rat striatal complex. There have been no corresponding studies of the effects of D-2 antagonists in primate species. Since all clinically effective antipsychotic drugs share D-2 receptor antagonism, it is important to define the extent to which these drugs may alter expression of c-fos or its protein product, Fos, in primates. We therefore examined the effects of administration of two D-2 receptor antagonists, haloperidol and metoclopramide, on Fos expression in the striatum and temporal cortices of the vervet monkey. Metoclopramide does not appear to possess significant antipsychotic efficacy but potently produces extrapyramidal side effects, while haloperidol is an effective antipsychotic drug that produces extrapyramidal side effects. Both drugs increased the number of Fos-like immunoreactive (Fos-li) neurons in the caudate nucleus and putamen; the numbers of Fos-li neurons in these regions were increased in both the patch and matrix compartments. Haloperidol but not metoclopramide increased the number of Fos-li neurons in the nucleus accumbens shell. Similarly, haloperidol but not metoclopramide increased the number of Fos-li neurons in the entorhinal cortex. Neither drug altered Fos expression in the inferior temporal cortex. These data suggest that the dorsolateral caudate nucleus and putamen may be sites at which D-2 receptor antagonists elicit extrapyramidal side effects, and the nucleus accumbens shell and entorhinal cortex may be loci at which the therapeutic actions of antipsychotic drugs are manifested. (C) 1996 Wiley-Liss, Inc. C1 YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06508. VET AFFAIRS MED CTR,PSYCHIAT SERV,WEST HAVEN,CT 06516. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT NEUROSCI,PITTSBURGH,PA 15213. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. RP Deutch, AY (reprint author), YALE UNIV,SCH MED,DEPT PSYCHIAT,CMHC,ROOM 306,34 PK ST,NEW HAVEN,CT 06508, USA. RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU NIMH NIH HHS [MH-25642, MH-43784, MH-45124] NR 55 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 1996 VL 23 IS 3 BP 182 EP 191 DI 10.1002/(SICI)1098-2396(199607)23:3<182::AID-SYN7>3.0.CO;2-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UU244 UT WOS:A1996UU24400007 PM 8807746 ER PT J AU Wang, W Hahn, KH Bishop, JF Gao, DQ Jose, PA Mouradian, MM AF Wang, W Hahn, KH Bishop, JF Gao, DQ Jose, PA Mouradian, MM TI Up-regulation of D-3 dopamine receptor mRNA by neuroleptics SO SYNAPSE LA English DT Article DE dopamine D-3 receptor; neuroleptic; antipsychotic; polymerase chain reaction ID MESSENGER-RNA LEVELS; RAT-BRAIN; D3; ISOFORM; TARGET AB The effects of 14 days neuroleptic treatment on the expression of the D-3 dopamine receptor gene was investigated in rats using a sensitive polymerase chain reaction assay. In olfactory tubercle, D-3 mRNA levels increased following haloperidol (40%), pimozide (56%), and sulpiride (63%) administration, and in nucleus accumbens, levels increased after haloperidol (50%) and sulpiride (50%). D-3 expression in the motor striatum did not change with any antagonist tested. Clozapine did not affect D-3 expression in any brain region. These data suggest that dopamine antagonists can regulate the expression of the D-3 receptor in a brain region selective manner. The findings also suggest that the motor complications of chronic antipsychotic therapy are not due to D-3 receptor up-regulation in the striatum. (C) 1996 Wiley-Liss, Inc.* C1 GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. RP Wang, W (reprint author), NINCDS,GENET PHARMACOL UNIT,EXPTL THERAPEUT BRANCH,NIH,BETHESDA,MD 20892, USA. OI Mouradian, M. Maral/0000-0002-9937-412X FU NIDDK NIH HHS [DK44756] NR 15 TC 22 Z9 22 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 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 1996 VL 23 IS 3 BP 232 EP 235 DI 10.1002/(SICI)1098-2396(199607)23:3<232::AID-SYN13>3.0.CO;2-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UU244 UT WOS:A1996UU24400013 PM 8807752 ER PT J AU Ward, JM AF Ward, JM TI Can so-called nongenotoxic hepatocarcinogens induce mouse liver nodules that are not neoplasms? SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material RP Ward, JM (reprint author), NCI,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1996 VL 24 IS 4 BP 505 EP 505 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA VB370 UT WOS:A1996VB37000015 PM 8864194 ER PT J AU Maronpot, RR AF Maronpot, RR TI Laboratory animal pathology - Emphasis on an area of relevance to the toxicologic pathologist SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material RP Maronpot, RR (reprint author), NIEHS,LAB ANIM PATHOL,POB 12233,111 ALEXANDER DR,MD-B3-06,RES TRIANGLE PK,NC 27709, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1996 VL 24 IS 4 BP 506 EP 506 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA VB370 UT WOS:A1996VB37000016 PM 8864195 ER PT J AU Dowsley, TF Ulreich, JB Bolton, JL Park, SS Forkert, PG AF Dowsley, TF Ulreich, JB Bolton, JL Park, SS Forkert, PG TI CYP2E1-dependent bioactivation of 1,1-dichloroethylene in murine lung: Formation of reactive intermediates and glutathione conjugates SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID VINYLIDENE-CHLORIDE; COVALENT BINDING; RAT-LIVER; METABOLISM; TOXICITY; CYTOCHROME-P-450; HEPATOCYTES; MICROSOMES; ETHANOL; OXIDATION AB We investigated the cytochrome P450-dependent metabolism of 1,1-dichloroethylene (DCE) in murine lung microsomal incubations, The metabolites were identified as their glutathione conjugates or hydrolyzed products, analyzed by HPLC and quantified with [C-14]DCE, We determined the relative quantities of DCE metabolites formed in lung microsomal incubations and compared them to those produced in liver. Furthermore, we used antibody inhibition experiments to investigate the CYP2E1-dependent metabolism of DCE in lung, Our results demonstrated that reactive intermediates were generated from DCE in the lung microsomal incubations. The DCE epoxide (12.6 +/- 1.4 pmol/mg protein/min) was the major metabolite formed and was identified as two glutathione conjugates, 2-(S-glutathionyl) acetyl glutathione and 2-S-glutathionyl acetate. Lower levels of the acetal of 2,2-dichloroacetaldehyde (3.6 +/- 0.25 pmol/mg protein/min) were detected. The ratio of acetal to DCE epoxide was higher in lung (0.30 +/- 0.04) than in liver (0.12 +/- 0.02). Preincubation of microsomes with a CYP2E1-inhibitory monoclonal antibody resulted in a maximum inhibition of 50% in the formation of both the acetal and the glutathione conjugates derived from the DCE epoxide, These data demonstrated that lung CYP2E1 metabolizes DCE to reactive intermediates of which the DCE epoxide is both the major metabolite formed and an efficient scavenger of glutathione, implicating it as an important toxic species mediating DCE-induced lung cytotoxicity. (C) 1996 Academic Press, Inc. C1 QUEENS UNIV,DEPT ANAT & CELL BIOL,KINGSTON,ON K7L 3N6,CANADA. UNIV ARIZONA,DEPT SURG,TUCSON,AZ 85724. UNIV ILLINOIS,DEPT MED CHEM & PHARMACOGNOSY,CHICAGO,IL 60612. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NIEHS NIH HHS [ES-04940] NR 31 TC 22 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL PY 1996 VL 139 IS 1 BP 42 EP 48 DI 10.1006/taap.1996.0141 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UW607 UT WOS:A1996UW60700006 PM 8685907 ER PT J AU Harry, GJ Schmitt, TJ Gong, ZL Brown, H Zawia, N Evans, HL AF Harry, GJ Schmitt, TJ Gong, ZL Brown, H Zawia, N Evans, HL TI Lead-induced alterations of glial fibrillary acidic protein (GFAP) in the developing rat brain SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; ASTROCYTE-SPECIFIC PROTEIN; DEVELOPMENTAL EXPRESSION; MESSENGER-RNA; INSITU HYBRIDIZATION; IMMATURE OLIGODENDROGLIA; INTERMEDIATE FILAMENTS; EXPOSURE; MOUSE; IMMUNOFLUORESCENCE AB The developing nervous system is preferentially vulnerable to lead exposure with alterations in neuronal and glial cells of the brain. The present study examined early lead-induced alterations in the developing astrocyte population by examination of the developmentally regulated astrocyte specific protein, glial fibrillary acidic protein (GFAP). A developmental profile (Postnatal Day (PND) 6, 9, 12, 15, 20, and 25) for GFAP mRNA was generated for the cortex and hippocampus of developing Long-Evans hooded male rats under various lead exposure conditions: (1) prenatal (Gestational Day 13 to birth), (2) postnatal (Postnatal Day 1 to Postnatal Day 20), or (3) perinatal (Gestational Day 13 to Postnatal Day 20) exposure to lead acetate (0.2% in the drinking water of the dam). Control GFAP mRNA levels displayed a developmentally regulated profile of expression. In the cortex this was characterized by a transient elevation in peak level between PND 9 and PND 15 followed by a decline to within adult levels by PND 25. Under all lead acetate exposure conditions, the cortex showed an increase in the peak level of expression and extended the time of elevation of GFAP mRNA until PND 20. Levels of GFAP were elevated at PND 60 but not as early as PND 28. In the control hippocampus, levels of GFAP mRNA gradually increased until PND 20 followed by a sharp decline at PND 25. Postnatal and perinatal lead exposure followed a similar pattern; however, levels declined earlier at PND 20. Following prenatal lead exposure, levels of GFAP mRNA showed an earlier peak at PND 12 and a decrease as early as PND 15. By PND 60 protein level for GFAP was elevated in the postnatal lead exposure group only. As demonstrated by GFAP immunoreactivity, these lead-induced elevations were not associated with astrocyte hypertrophy. Following a physical injury in the cortex, astrocyte reactivity was similar between lead-exposed and control rats. These data suggest an alteration in the timing of astrocyte differentiation and maturation in the brain following developmental lead exposure. (C) 1996 Academic Press, Inc. C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27515. NYU,MED CTR,NELSON INST ENVIRONM MED,LAB NEURAL TOXICOL,TUXEDO PK,NY 10987. RP Harry, GJ (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,POB 12233,MD C1-04,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [T32 ES07126, N01-ES-25331] NR 64 TC 45 Z9 47 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL PY 1996 VL 139 IS 1 BP 84 EP 93 DI 10.1006/taap.1996.0145 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UW607 UT WOS:A1996UW60700010 PM 8685912 ER PT J AU Koonin, EV AF Koonin, EV TI A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ESCHERICHIA-COLI; PHOSPHATIDYLSERINE SYNTHASE; GENE; YEAST; PURIFICATION; SEARCH RP Koonin, EV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 25 TC 118 Z9 120 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1996 VL 21 IS 7 BP 242 EP 243 DI 10.1016/S0968-0004(96)30024-8 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX945 UT WOS:A1996UX94500002 PM 8755242 ER PT J AU Hengen, PN AF Hengen, PN TI Pouring sequencing gels the old-fashioned way SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 8 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 JUL PY 1996 VL 21 IS 7 BP 273 EP 274 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX945 UT WOS:A1996UX94500011 PM 8755250 ER PT J AU Barry, CE Mdluli, K AF Barry, CE Mdluli, K TI Drug sensitivity and environmental adaptation of mycobacterial cell wall components SO TRENDS IN MICROBIOLOGY LA English DT Article ID CATALASE-PEROXIDASE GENE; TUBERCULOSIS H37RA; ACID BIOSYNTHESIS; ESCHERICHIA-COLI; MYCOLIC ACIDS; RESISTANCE; ARABINOGALACTAN; SMEGMATIS; GROWTH; PERMEABILITY AB The intrinsic resistance of many mycobacterial species to chemotherapy is largely attributable to their impermeable cell wall. The composition of the cell wall of a particular species appears to be influenced by the environmental niche that the species occupies. The complex regulatory and biosynthetic pathways involved in cell wall biosynthesis and construction offer useful chemotherapeutic targets against mycobacteria. C1 NIAID,TB RES UNIT,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 58 TC 64 Z9 64 U1 3 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JUL PY 1996 VL 4 IS 7 BP 275 EP 281 DI 10.1016/0966-842X(96)10031-7 PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA UY305 UT WOS:A1996UY30500007 PM 8829336 ER PT J AU Kuhar, MJ Pilotte, NS AF Kuhar, MJ Pilotte, NS TI Neurochemical changes in cocaine withdrawal SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID RAT NUCLEUS-ACCUMBENS; BASAL EXTRACELLULAR DOPAMINE; TYROSINE-HYDROXYLASE; REWARD REGIONS; MESSENGER-RNA; BRAIN; ABSTINENCE; ADDICTION; MORPHINE; SENSITIZATION AB Cocaine withdrawal in animals causes a transient increase followed by a long-lasting decrease in mesolimbic dopamine transporters, dopamine efflux and the number of dopamine cells firing spontaneously. Other changes in the nucleus accumbens and frontal cortex also suggest alterations in dopamine-receptive neurones and circuits. In humans, brain imaging has provided evidence for some similar, long-lasting changes in dopaminergic neurones and innervated areas, These results suggest a protracted biochemical abstinence syndrome for cocaine. In this review, Michael Kuhar and Nancy Pilotte focus on biochemical changes that occur following withdrawal from repeated cocaine administration. A key question for treatment is whether (some of) these persistent changes underlie withdrawal symptomatology such as anhedonia and relapse. C1 NIDA,NEUROSCI BRANCH,ADDICT RES CTR,BALTIMORE,MD 21224. RP Kuhar, MJ (reprint author), EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322, USA. NR 53 TC 127 Z9 127 U1 2 U2 3 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 JUL PY 1996 VL 17 IS 7 BP 260 EP 264 DI 10.1016/S0165-6147(96)10024-9 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UY792 UT WOS:A1996UY79200005 PM 8756185 ER PT J AU Winokur, PL McBride, AA AF Winokur, PL McBride, AA TI The transactivation and DNA binding domains of the BPV-1 E2 protein have different roles in cooperative origin binding with the E1 protein SO VIROLOGY LA English DT Article ID BOVINE PAPILLOMAVIRUS; TRANSCRIPTIONAL ACTIVATION; REPLICATION PROTEIN; TERMINAL DOMAIN; GENE-PRODUCT; INVITRO; DIMER; TRANSFORMATION; SEPARATION; E2-PROTEIN AB The bovine papillomavirus E2 transactivator protein enhances the ability of the E1 protein to bind to the viral origin of replication which contains an E1 binding site flanked by two E2 binding sites. To determine which regions and functions of the E2 protein are important for this cooperative interaction, a series of mutated E2 proteins were assayed for their ability to enhance E1 origin-specific binding. Cooperative origin binding required at least one E2 DNA binding site, an intact functional E2 DNA binding domain, and an intact transactivation domain. The hinge region of the E2 proteins was dispensable for this activity. To further examine the role of the E2 C-terminal domain, a series of chimeric proteins were generated that substituted the yeast GAL4 DNA binding domain for the E2 DNA binding domain. These chimeric proteins were able to cooperatively bind to a hybrid origin that contained GAL4 binding sites in place of the E2 binding sites, These studies indicate that the E2 transactivation domain is sufficient for interaction with the E1 protein and that the E2 DNA binding domain is required for interaction with origin DNA sequences. (C) 1996 Academic Press, Inc C1 NIAID,VIRAL DIS LAB,NATL INST HLTH,BETHESDA,MD 20892. UNIV IOWA,VET ADM MED CTR,IOWA CITY,IA 52242. UNIV IOWA,DEPT INTERNAL MED,IOWA CITY,IA 52242. OI McBride, Alison/0000-0001-5607-5157 NR 49 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 1 PY 1996 VL 221 IS 1 BP 44 EP 53 DI 10.1006/viro.1996.0351 PG 10 WC Virology SC Virology GA UW442 UT WOS:A1996UW44200005 PM 8661413 ER PT J AU Karasev, AV Nikolaeva, OV Mushegian, AR Lee, RF Dawson, WO AF Karasev, AV Nikolaeva, OV Mushegian, AR Lee, RF Dawson, WO TI Organization of the 3'-terminal half of beet yellow stunt virus genome and implications for the evolution of closteroviruses SO VIROLOGY LA English DT Article ID STRAND RNA VIRUSES; NUCLEOTIDE-SEQUENCE; PLANT-VIRUSES; PROTEINS; PHYLOGENY; BINDING; GENE AB The 3'-terminal half of the beet yellow stunt virus (BYSV) genome, 10,545 nt, has been cloned and sequenced. The sequenced portion of the BYSV genome encompasses 10 open reading frames (ORFs) and 241 nt of the 3' untranslated region. The sequence spans, in the 5' to 3' direction, the C-terminal region of the replication-associated polyprotein gene (ORF la) which includes the set of motifs typical of helicases (HEL), the entire 53-kDa polymerase (RdRp) gene (ORF Ib), and genes encoding 30-kDa (ORF 2), 6-kDa (ORF 3), 66-kDa (ORF 4), 61-kDa (ORF 5), 25-kDa (ORF 6), 23.7-kDa (coat protein, CP) (ORF 7), 18-kDa (ORF 8), and 22-kDa (ORF 9) proteins. The double-stranded RNA ''replicative form'' of the BYSV was demonstrated to have a nontemplate G residue at the 3' terminus of the (+) strand. The RdRp of BYSV is presumably expressed via a +1 ribosomal frameshift. The five-gene module conserved among closteroviruses was identified in BYSV; it includes a gene array coding for a 6-kDa small hydrophobic protein, a 66-kDa homolog of the cellular HSP70 heat shock proteins, a 61-kDa protein, and a 25-kDa diverged copy of the CP followed by the CP gene itself. Phylogenetic analysis of the replication-associated HEL and RdRp domains as well as proteins from the five-gene module demonstrated the closest relationship between BYSV and two other closteroviruses, beet yellows (BYV) and citrus tristeza (CTV) viruses. Like CTV, the BYSV genome contains a 30-kDa protein gene between the RdRp and the 6-kDa protein genes, and like BW it has only two genes downstream of the CP gene. The organization of the BYSV genome appears to be intermediate between BW and CN, which suggests that these three viruses might represent three distinct but probably close stages in the closterovirus evolution. (C) 1996 Academic Press, Inc. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. RP Karasev, AV (reprint author), UNIV FLORIDA,CTR CITRUS RES & EDUC,700 EXPT STN RD,LAKE ALFRED,FL 33850, USA. OI Mushegian, Arcady/0000-0002-6809-9225 NR 46 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 1 PY 1996 VL 221 IS 1 BP 199 EP 207 DI 10.1006/viro.1996.0366 PG 9 WC Virology SC Virology GA UW442 UT WOS:A1996UW44200020 PM 8661428 ER PT J AU Muramatsu, S Mizukami, H Young, NS Brown, KE AF Muramatsu, S Mizukami, H Young, NS Brown, KE TI Nucleotide sequencing and generation of an infectious clone of adeno-associated virus 3 SO VIROLOGY LA English DT Article ID PARVOVIRUS; PROMOTER; TRANSCRIPTION; PROTEINS; ELEMENT; BINDING; GENOME; MOTIF; CELLS AB We have determined the complete nucleotide sequences of adeno-associated virus 3 (AAV-3) and generated an infectious clone. The single-stranded DNA genome of AAV-3 is 4726 nucleotides in length, The positive strand contains two large open reading frames; the left open reading frame encodes the nonstructural proteins and the right open reading frame encodes the structural proteins. The coding regions are flanked by identical inverted terminal repeat sequences containing palindromes, AAV-3 has little homology with the autonomous parvoviruses or erythroviruses but has 82% overall sequence homology with AAV-2. At the amino acid level there was 88% homology with AAV-2 nonstructural (Rep) proteins and 87% homology with AAV-2 capsid proteins. In addition, AAV-3 differed importantly from AAV-2 in the lack of a typical promoter sequence (TATA box) at p40 and the presence of the consensus sequence for adenovirus-related transcription factor E4F binding within the upstream region of the p5 promoter. These results suggest that AAV-3 not only consists of serologically distinct structural proteins but that viral propagation also may be controlled by different gene regulatory elements at the transcription level. The infectious clone confirmed the sequence and may be useful for developing new vectors for gene therapy. (C) 1996 Academic Press, Inc. RP Muramatsu, S (reprint author), NHLBI,HEMATOL BRANCH,NIH,BLDG 10 RM 7C218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Mizukami, Hiroaki/D-7674-2013; OI Mizukami, Hiroaki/0000-0001-8954-874X; Muramatsu, Shinichi/0000-0002-3185-7790 NR 36 TC 103 Z9 104 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 1 PY 1996 VL 221 IS 1 BP 208 EP 217 DI 10.1006/viro.1996.0367 PG 10 WC Virology SC Virology GA UW442 UT WOS:A1996UW44200021 PM 8661429 ER PT J AU Krauzlis, RJ Miles, FA AF Krauzlis, RJ Miles, FA TI Decreases in the latency of smooth pursuit and saccadic eye movements produced by the ''gap paradigm'' in the monkey SO VISION RESEARCH LA English DT Article DE pursuit; saccade; latency; fixation; attention ID DORSOLATERAL PONTINE NUCLEUS; OCULAR FOLLOWING RESPONSES; HUMAN EXPRESS SACCADES; SHORT REACTION-TIMES; SUPERIOR COLLICULUS; ALERT MONKEY; VESTIBULOOCULAR REFLEX; NEURONAL-ACTIVITY; VISUAL-ATTENTION; FIXATION CELLS AB The initiation of both pursuit and saccades was affected by the presence of a temporal gap between the disappearance of a fixated visual target and the appearance of a second, eccentric, target. For pursuit, the gap paradigm produced a modest (20 msec) decrease in latency, For saccades, the gap paradigm produced a similar modest decrease in the latency of some saccades, but also revealed a population of very short latency ''express'' saccades. The modest changes in the latency of pursuit and regular saccades displayed a similar dependence on gap duration, with the largest decreases produced by gaps of 200-300 msec. The gap paradigm did not produce ''express'' pursuit, even though express saccades could be elicited on interleaved trials. RP Krauzlis, RJ (reprint author), NIH, SENSORIMOTOR RES LAB, BLDG 49, ROOM 2A-50, BETHESDA, MD 20982 USA. NR 52 TC 61 Z9 61 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD JUL PY 1996 VL 36 IS 13 BP 1973 EP 1985 DI 10.1016/0042-6989(95)00307-X PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA UV007 UT WOS:A1996UV00700013 PM 8759437 ER PT J AU Ono, S Hatanaka, T Hotta, H Satoh, T Gonzalez, FJ Tsutsui, M AF Ono, S Hatanaka, T Hotta, H Satoh, T Gonzalez, FJ Tsutsui, M TI Specificity of substrate and inhibitor probes for cytochrome P450s: Evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes SO XENOBIOTICA LA English DT Article ID VACCINIA VIRUS; HYDROXYLATION; RAT; IDENTIFICATION; FORMALDEHYDE; TOLBUTAMIDE; ASSOCIATION; MEPHENYTOIN; ACTIVATION; SUBFAMILY AB 1. We evaluated the specificity of 15 substrates and 14 inhibitors of the cytochrome P450s using nine human P450 forms expressed in HepG2 cells using a recombinant vaccinia virus and also in human liver microsomes. 2. Coumarin, 7-ethoxyresorufin, 7-benzyloxyresorufin, tolbutamide, aniline and diazepam were form-selective substrates towards CYP2A6, the CYP1A subfamily, CYP2B6, the CYP2C subfamily, CYP2E1 and the CYP3A subfamily respectively. However, a selective substrate for CYP2D6 was not found among the chemicals tested. 3. SKF-525A inhibited > 40 % of the metabolic activity of all substrates tested, and the inhibitory effects differed among P450 forms. Sulphaphenazole, 7,8-benzoflavone, quinidine and troleandomycin were selective inhibitors of the CYP2C subfamily (except CYP2C19), the CYP1A subfamily, CYP2D6 and the CYP3A subfamily respectively. Methoxsalen (CYP2A6 inhibitor) inhibited the metabolic activity of CYP1A2 as well as that of CYP2A6. Diethyldithiocarbamate (CYP2E1 inhibitor) inhibited the metabolic activities of CYP2A6 and CYP2C19 in addition to that of CYP2E1. 4. Our results indicated that substrates and inhibitors reported as P450 selective probes are not necessarily specific for individual human P450 forms. These results may provide useful information regarding human P450 substrates and inhibitors in vitro using human liver microsomal samples. C1 CHIBA UNIV,FAC PHARMACEUT SCI,BIOCHEM PHARMACOL & BIOTOXICOL LAB,CHIBA 260,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Ono, S (reprint author), AMERSHAM KK,CENT LAB RES & DEV,2802-1 HIRATSUKA,CHIBA 27014,JAPAN. NR 42 TC 201 Z9 203 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUL PY 1996 VL 26 IS 7 BP 681 EP 693 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UW260 UT WOS:A1996UW26000002 PM 8819299 ER PT J AU Steinert, PM AF Steinert, PM TI Intermediate filaments in health and disease SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSMISSION ELECTRON-MICROSCOPY; EPIDERMAL KERATIN FILAMENTS; COILED-COIL MOLECULES; SUPEROXIDE-DISMUTASE; DYNAMIC ASPECTS; NUCLEAR LAMINA; NETWORKS; PHOSPHORYLATION; EXPRESSION AB Intermediate filaments constitute one of the major classes of cytoskeletal proteins of mammalian cells. The 40 or more known intermediate filament proteins have been classified into five types which show very specific rules of expression in specialized cell types, and include: type I and type II keratins of epithelial cells; type III vimentin (mesenchymal cells), desmin (muscle), glial fibrillary acidic protein (astroglia), and peripherin (peripheral neurones); type IV neurofilaments of neuronal cell types; and type V nuclear lamins, Intermediate filaments differ from ubiquitous microfilaments (actin) and microtubules (tubulin) in several important ways, including their structures, intracellular dynamics, and functions. Notably, intermediate filament chains possess a characteristic central alpha-helical domain that forms coiled-coil rods which in turn assemble into 10-15 nm diameter filaments, The end domains which flank the rod domain are highly variable in sequence and confer specific functions to the filaments in different cell types, Recently, a number of diseases have been identified in human that involve mutations in genes encoding intermediate filament chains. These include seven different keratin diseases, usually caused by mutations in rod domain sequences which often result in serious skin (epidermal) abnormalities; and many cases of sporadic amyotrophic lateral sclerosis caused by mutations in the end domain sequences of neurofilament chains. C1 NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NR 61 TC 4 Z9 4 U1 2 U2 6 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0378-8512 J9 EXP MOL MED JI Exp. Mol. Med. PD JUN 30 PY 1996 VL 28 IS 2 BP 55 EP 63 PG 9 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA UV906 UT WOS:A1996UV90600001 ER PT J AU ChoChung, YS AF ChoChung, YS TI Protein kinase A type I-directed antisense inhibition of cancer growth SO MOLECULES AND CELLS LA English DT Review ID RI-ALPHA-SUBUNIT; MAMMARY EPITHELIAL-CELLS; SELECTIVE CAMP ANALOGS; HL-60 LEUKEMIA-CELLS; CYCLIC-AMP ANALOGS; REGULATORY SUBUNIT; GENE-EXPRESSION; BINDING-PROTEINS; MESSENGER-RNA; ADENOSINE-MONOPHOSPHATE RP ChoChung, YS (reprint author), NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 59 TC 0 Z9 0 U1 0 U2 0 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD JUN 30 PY 1996 VL 6 IS 3 BP 231 EP 238 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UU762 UT WOS:A1996UU76200001 ER PT J AU Geller, N Freedman, L Lee, YJ Dersimonian, R AF Geller, N Freedman, L Lee, YJ Dersimonian, R TI Conference on meta-analysis in the design and monitoring of clinical trials - Preface SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. NICHHD,BETHESDA,MD. RP Geller, N (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1233 EP 1233 PG 1 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600001 ER PT J AU DerSimonian, R AF DerSimonian, R TI Meta-analysis in the design and monitoring of clinical trials SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Conference on Meta-Analysis in the Design and Monitoring of Clinical Trials CY JUN 23-24, 1994 CL ROCKVILLE, MD SP Data & Safety Monitoring Board CPEP ID CALCIUM SUPPLEMENTATION; PUBLICATION BIAS; PREGNANCY; HYPERTENSION; PREECLAMPSIA; PREVENTION; QUALITY; RISK AB Results from external studies often play an important role in many aspects of a clinical trial. Their incorporation into the decision making process of a trial, however, is rarely conducted in a formal manner. This conference will address what formal role, if any, meta-analytic summaries of external results should have in the design and monitoring of an ongoing trial. This introductory presentation describes in detail the example from obstetric research which motivated the conference topic, and, in a Bayesian framework, summarizes the general implications of formally incorporating meta-analytic results into the design and analysis of a new trial. RP DerSimonian, R (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,EXECUT BLDG 7B13P,6100 EXECUT BLVD MSC 7510,BETHESDA,MD 20892, USA. NR 34 TC 110 Z9 110 U1 2 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1237 EP 1248 DI 10.1002/(SICI)1097-0258(19960630)15:12<1237::AID-SIM301>3.0.CO;2-N PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600002 PM 8817798 ER PT J AU Freedman Simon Pocock DerSimonian Brown DeMets Louis Chalmers Collins Clemens George Feinstein Ellenberg Olkin AF Freedman Simon Pocock DerSimonian Brown DeMets Louis Chalmers Collins Clemens George Feinstein Ellenberg Olkin TI Meta-analysis in the design and monitoring of clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material ID ADJUVANT THERAPY; FLUOROURACIL; LEVAMISOLE; CARCINOMA C1 LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. NICHHD,BETHESDA,MD. STANFORD UNIV,SCH MED,STANFORD,CA 94305. UNIV WISCONSIN,MADISON,WI 53706. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. METAWORKS INC,LUDINGTON,MI 49431. RADCLIFFE INFIRM,OXFORD,ENGLAND. DUKE UNIV,MED CTR,DURHAM,NC 27706. YALE UNIV,SCH MED,NEW HAVEN,CT. US FDA,ROCKVILLE,MD. RP Freedman (reprint author), NCI,BETHESDA,MD 20892, USA. NR 6 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 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1249 EP 1252 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600003 ER PT J AU Meier Olkin Begg George Ellenberg Collins Freedman Pocock Chalmers AF Meier Olkin Begg George Ellenberg Collins Freedman Pocock Chalmers TI Meta-analysis: Current issues in research synthesis - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material ID CORONARY THROMBOLYSIS C1 STANFORD UNIV,STANFORD,CA 94305. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. DUKE UNIV,MED CTR,DURHAM,NC. US FDA,ROCKVILLE,MD 20857. RADCLIFFE INFIRM,OXFORD OX2 6HE,ENGLAND. NCI,BETHESDA,MD 20892. LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. METAWORKS INC,LUDINGTON,MI 49431. RP Meier (reprint author), COLUMBIA UNIV,NEW YORK,NY 10027, USA. NR 13 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 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1259 EP 1262 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600005 ER PT J AU DeMets Temple Chalmers Begg Collins Olkin Freedman Ellenberg Geller Berendes Feinstein George Meier AF DeMets Temple Chalmers Begg Collins Olkin Freedman Ellenberg Geller Berendes Feinstein George Meier TI Changes in clinical trials mandated by the advent of meta-analysis - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 US FDA,ROCKVILLE,MD. METAWORKS INC,LUDINGTON,MI 49431. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NICHHD,BETHESDA,MD. STANFORD UNIV,STANFORD,CA 94305. NCI,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. YALE UNIV,SCH MED,NEW HAVEN,CT. DUKE UNIV,MED CTR,DURHAM,NC. COLUMBIA UNIV,NEW YORK,NY. RP DeMets (reprint author), UNIV WISCONSIN,MADISON,WI 53706, USA. NR 6 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 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1269 EP 1272 DI 10.1002/(SICI)1097-0258(19960630)15:12<1269::AID-SIM306>3.0.CO;2-# PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600007 ER PT J AU Ellenberg Pocock Lee Olkin Collins Meier Louis George Simon AF Ellenberg Pocock Lee Olkin Collins Meier Louis George Simon TI The role of external evidence in data monitoring of a clinical trial - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 LONDON SCH HYG & TROP MED,LONDON,ENGLAND. NICHHD,BETHESDA,MD. STANFORD UNIV,STANFORD,CA 94305. RADCLIFFE INFIRM,OXFORD OX2 6HE,ENGLAND. COLUMBIA UNIV,NEW YORK,NY. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN. DUKE UNIV,MED CTR,DURHAM,NC. NCI,BETHESDA,MD 20892. RP Ellenberg (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 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 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1295 EP 1297 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600011 ER PT J AU Friedman Begg Feinstein Chalmers Meier Freedman Pocock Ellenberg Brown Louis Collins Olkin DerSimonian AF Friedman Begg Feinstein Chalmers Meier Freedman Pocock Ellenberg Brown Louis Collins Olkin DerSimonian TI The role of meta-analysis in monitoring clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 METAWORKS INC,LUDINGTON,MI 49431. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RADCLIFFE INFIRM,OXFORD,ENGLAND. US FDA,ROCKVILLE,MD 20857. YALE UNIV,SCH MED,NEW HAVEN,CT. COLUMBIA UNIV,NEW YORK,NY. LONDON SCH HYG & TROP MED,LONDON,ENGLAND. STANFORD UNIV,SCH MED,STANFORD,CA. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN. NICHHD,BETHESDA,MD. RP Friedman (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 1 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 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1307 EP 1311 DI 10.1002/(SICI)1097-0258(19960630)15:12<1307::AID-SIM312>3.0.CO;2-J PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600013 ER PT J AU Geller, NL AF Geller, NL TI Role of meta-analyses in design and monitoring of randomized clinical trials: Summary of first day of the workshop SO STATISTICS IN MEDICINE LA English DT Editorial Material RP Geller, NL (reprint author), NHLBI,OFF BIOSTAT RES,ROCKLEDGE 2,ROOM 8210,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1313 EP 1315 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600014 ER PT J AU Brown Friedman Temple Collins Simon Feinstein Chalmers Begg Pocock Freedman Meier George DeMets Ellenberg Clemens Berendes AF Brown Friedman Temple Collins Simon Feinstein Chalmers Begg Pocock Freedman Meier George DeMets Ellenberg Clemens Berendes TI Role of meta-analyses in design and monitoring of randomized clinical trials: Summary of first day of the workshop - Concluding discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. RADCLIFFE INFIRM,OXFORD OX2 6HE,ENGLAND. YALE UNIV,SCH MED,NEW HAVEN,CT. METAWORKS INC,LUDINGTON,MI 49431. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. LONDON SCH HYG & TROP MED,LONDON,ENGLAND. COLUMBIA UNIV,NEW YORK,NY. DUKE UNIV,MED CTR,DURHAM,NC. UNIV WISCONSIN,MADISON,WI 53706. NICHHD,BETHESDA,MD. RP Brown (reprint author), STANFORD UNIV,SCH MED,STANFORD,CA 94305, USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1996 VL 15 IS 12 BP 1317 EP 1323 DI 10.1002/(SICI)1097-0258(19960630)15:12<1317::AID-SIM314>3.0.CO;2-C PG 7 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UU766 UT WOS:A1996UU76600015 ER PT J AU Malhotra, AK Goldman, D Buchanan, R Breier, A Pickar, D AF Malhotra, AK Goldman, D Buchanan, R Breier, A Pickar, D TI 5HT(2a) receptor T102C polymorphism and schizophrenia SO LANCET LA English DT Letter RP Malhotra, AK (reprint author), NIMH,UNIT PHARMACOGENET,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 5 TC 26 Z9 27 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 JUN 29 PY 1996 VL 347 IS 9018 BP 1830 EP 1831 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UU469 UT WOS:A1996UU46900042 PM 8667937 ER PT J AU Grem, JL Politi, PM Berg, SL Benchekroun, NM Patel, M Balis, FM Sinha, BK Dahut, W Allegra, CJ AF Grem, JL Politi, PM Berg, SL Benchekroun, NM Patel, M Balis, FM Sinha, BK Dahut, W Allegra, CJ TI Cytotoxicity and DNA damage associated with pyrazoloacridine in MCF-7 breast cancer cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE pyrazoloacridine; DNA intercalation; DNA binding; DNA fragmentation ID TOPOISOMERASE-II INHIBITORS; TUMOR-CELLS; DIFFERENTIAL INDUCTION; SOLID TUMORS; RESISTANCE; LINES; FRAGMENTATION; REQUIREMENT; MECHANISMS; ETOPOSIDE AB We examined the effects of pyrazoloacridine (PZA), an investigational anticancer agent in clinical trials, on cytotoxicity, DNA synthesis, and DNA damage in MCF-7 human breast carcinoma cells. With PZA concentrations ranging from 0.5 to 50 mu M for durations of 3-72 hr, cytotoxicity increased in proportion to the total PZA exposure (concentration x time). Inhibition of DNA and RNA syntheses increased with increasing PZA concentration x time (mu M . hr). A 24-hr exposure to 1 and 10 mu M PZA reduced DNA synthesis to 62 and 5% of control, respectively, decreased the proportion of cells in S phase with accumulation of cells in G(2) + M phase, and inhibited cell growth at 72 hr by 68 and 100%. Newly synthesized DNA was more susceptible to damage during PZA exposure, with subsequent induction of parental DNA damage. Significant damage to newly synthesized DNA as monitored by alkaline elution was evident after a 3-hr exposure to greater than or equal to 5 mu M PZA. Longer PZA exposures (greater than or equal to 10 mu M for 16 hr) were required to elicit damage to parental DNA. Induction of single-strand breaks in parental DNA correlated closely with induction of double-strand breaks and detachment of cells from the monolayer. PZA-mediated DNA fragmentation was not accompanied by the generation of oligonucleosomal laddering in MCF-7 cells, but induction of very high molecular weight DNA fragmentation (0.5 to 1 Mb) was detected by pulsed-field gel electrophoresis. In vitro binding of PZA to linear duplex DNA (1 kb DNA ladder) and closed, circular plasmid DNA was demonstrated by a shift in migration during agarose electophoresis. PZA interfered with topoisomerase I- and II-mediated relaxation of plasmid DNA in a cell-fret system, but the cytotoxic effects of PZA did not appear to involve a direct interaction with topoisomerase I or II (stabilization of the topoisomerase I- or II-DNA cleavable complex). PZA-mediated cytotoxicity correlated strongly with inhibition of DNA and RNA syntheses, and damage to both nascent and parental DNA. Neither the cytotoxicity of PZA nor induction of double-stranded DNA fragmentation was prevented by aphidicolin, indicating that PZA-mediated lethality occurred in the absence of DNA replication. Since free radical formation was not detected, induction of nascent and parental DNA damage appeared to be a consequence of the avid binding of PZA to DNA, presumably by interfering with the access of replication, repair, and transcription enzyme complexes. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. NR 36 TC 22 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 28 PY 1996 VL 51 IS 12 BP 1649 EP 1659 DI 10.1016/0006-2952(96)00130-X PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UM292 UT WOS:A1996UM29200008 PM 8687480 ER PT J AU Martinez, JM Papp, LA Coplan, JD Anderson, DE Klein, DF Gorman, JM AF Martinez, JM Papp, LA Coplan, JD Anderson, DE Klein, DF Gorman, JM TI Ambulatory monitoring of respiration in panic disorder SO BIOLOGICAL PSYCHOLOGY LA English DT Meeting Abstract C1 COLUMBIA UNIV COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,NEW YORK,NY 10032. COLUMBIA UNIV,NEW YORK,NY 10027. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JUN 28 PY 1996 VL 43 IS 3 BP 37 EP 37 PG 2 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA UX952 UT WOS:A1996UX95200040 ER PT J AU Mueser, TC Nossal, NG Hyde, CC AF Mueser, TC Nossal, NG Hyde, CC TI Structure of bacteriophage T4 RNase H, a 5' to 3' RNA-DNA and DNA-DNA exonuclease with sequence similarity to the RAD2 family of eukaryotic proteins SO CELL LA English DT Article ID ESCHERICHIA-COLI; REPLICATION; POLYMERASE AB Bacteriophage T4 RNase H is a 5' to 3' exonuclease that removes RNA primers from the lagging strand of the DNA replication fork and is a member of the RAD2 family of eukaryotic and prokaryotic replication and repair nucleases. The crystal structure of the full-length native form of T4 RNase H has been solved at 2.06 Angstrom resolution in the presence of Mg2+ but in the absence of nucleic acids. The most conserved residues are clustered together in a large cleft with two Mg2+ in the proposed active site. This structure suggests the way in which the widely separated conserved regions in the larger nucleotide excision repair proteins, such as human XPG, could assemble into a structure like that of the smaller replication nucleases. C1 NIDDK,NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP Mueser, TC (reprint author), NIAMSD,NIH,STRUCT BIOL RES LAB,BETHESDA,MD 20892, USA. NR 42 TC 152 Z9 154 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 28 PY 1996 VL 85 IS 7 BP 1101 EP 1112 DI 10.1016/S0092-8674(00)81310-0 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV484 UT WOS:A1996UV48400016 PM 8674116 ER PT J AU Edelmann, W Cohen, PE Kane, M Lau, K Morrow, B Bennett, S Umar, A Kunkel, T Cattoretti, G Chaganti, R Pollard, JW Kolodner, RD Kucherlapati, R AF Edelmann, W Cohen, PE Kane, M Lau, K Morrow, B Bennett, S Umar, A Kunkel, T Cattoretti, G Chaganti, R Pollard, JW Kolodner, RD Kucherlapati, R TI Meiotic pachytene arrest in MLH1-deficient mice SO CELL LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; SYNAPTONEMAL COMPLEX; COLON-CANCER; GENES; MUTATIONS; LOCUS; IDENTIFICATION; HOMOLOG AB Germ line mutations in DNA mismatch repair genes including MLH1 cause hereditary nonpolyposis colon cancer. To understand the role of MLH1 in normal growth and development, we generated mice that have a null mutation of this gene. Mice homozygous for this mutation show a replication error phenotype, and extracts of these cells are deficient in mismatch repair activity. Homozygous mutant males show normal mating behavior but have no detectable mature sperm. Examination of meiosis in these males reveals that the cells enter meiotic prophase and arrest at pachytene. Homozygous mutant females have normal estrous cycles and reproductive and mating behavior but are infertile. The phenotypes of the mlh1 mutant mice are distinct from those deficient in msh2 and pms2. The different phenotypes of the three types of mutant mice suggest that these three genes may have independent functions in mammalian meiosis. C1 ALBERT EINSTEIN COLL MED,DEPT DEV & MOL BIOL,BRONX,NY 10467. DANA FARBER CANC INST,BOSTON,MA 02115. NIEHS,RES TRIANGLE PK,NC 27709. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY. MEM SLOAN KETTERING CANC CTR,DEPT GENET,NEW YORK,NY 10021. RP Edelmann, W (reprint author), ALBERT EINSTEIN COLL MED,DEPT MOLEC GENET,BRONX,NY 10467, USA. OI Cattoretti, Giorgio/0000-0003-3799-3221 FU NCI NIH HHS [CA 67944]; NICHD NIH HHS [HD/AI 30280]; NIGMS NIH HHS [GM 50006] NR 58 TC 412 Z9 423 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 28 PY 1996 VL 85 IS 7 BP 1125 EP 1134 DI 10.1016/S0092-8674(00)81312-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV484 UT WOS:A1996UV48400018 PM 8674118 ER PT J AU Gvakharia, BO Hanson, E Koonin, EK Mathews, CK AF Gvakharia, BO Hanson, E Koonin, EK Mathews, CK TI Identification of a second functional glutaredoxin encoded by the bacteriophage T4 genome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBONUCLEOTIDE REDUCTASE; MUTANT THIOREDOXINS; THIOLTRANSFERASE; SEQUENCE; ENZYME; ACID AB Thioredoxins and glutaredoxins are small ubiquitous redox proteins that were discovered as hydrogen donors for ribonucleotide reductase, the key enzyme for deoxyribonucleotide biosynthesis. Some organisms encode more than one redox protein. In this study, we demonstrate that an open reading frame in the bacteriophage T4 genome, reported earlier and designated as Y55.7 (Tomaschewski, J., and Ruger, W. (1987) Nucleic Acids Res. 15, 3632-3633), encodes a second functional redox protein. Gene y55.7 was cloned and expressed in Escherichia coli. Purified Y55.7 protein had glutathione-dependent thioltransferase and dehydroascorbate reductase activities indicative of a functional glutaredoxin. The protein is expressed at all stages of the T4 infection cycle and can serve as a hydrogen donor for the phage ribonucleotide reductase in in vitro experiments. C1 OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,CORVALLIS,OR 97331. NATL LIB MED,NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. FU NIGMS NIH HHS [GM 87508] NR 32 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15307 EP 15310 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900003 PM 8662944 ER PT J AU Netto, LES Chae, HZ Kang, SW Rhee, SG Stadtman, ER AF Netto, LES Chae, HZ Kang, SW Rhee, SG Stadtman, ER TI Removal of hydrogen peroxide by thiol-specific antioxidant enzyme (TSA) is involved with its antioxidant properties - TSA possesses thiol peroxidase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; OXIDATION; PROTEIN AB The thiol-specific antioxidant protein (TSA) protects glutamine synthetase from inactivation by a metal-catalyzed oxidation (MCO) system comprised of dithiothreitol (DTT)/Fe3+/O-2 but not by the ascorbate/Fe3+/O-2 MCO system. The removal of sulfur-centered radicals or H2O2 has been proposed as the protective mechanism of TSA. Like catalase, TSA prevents the initiation of the rapid O-2 uptake phase during MCO of DTT but causes only partial inhibition when added after the reaction is well into the propagation phase. Stoichiometric studies showed that the antioxidant property of TSA is, at least in part, due to its ability to catalyze the destruction of H2O2 by the overall reaction 2 RSH + H2O2 --> RSSR + H2O. Results of kinetic studies demonstrate that the removal of H2O2 by TSA correlates with its ability to protect glutamine synthetase from inactivation. In the presence of thioredoxin, TSA is more active, whereas C170S (an active mutant of TSA in which cysteine 170 was replaced by a serine) and open reading frame 6 (a human antioxidant protein homologous to TSA with only one conserved cysteine residue) are only slightly affected. The thiol specificity of the protective activity of TSA derives from the fact that the oxidized form of TSA can be converted back to its sulfhydryl form by treatment with thiols but not by ascorbate. C1 NHLBI,NIH,BIOCHEM LAB,BETHESDA,MD 20892. NHLBI,NIH,LAB CELL SIGNALLING,BETHESDA,MD 20892. RI Netto, Luis/A-3783-2008 OI Netto, Luis/0000-0002-4250-9177 NR 26 TC 174 Z9 177 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15315 EP 15321 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900005 ER PT J AU Barr, DP Gunther, MR Deterding, LJ Tomer, KB Mason, RP AF Barr, DP Gunther, MR Deterding, LJ Tomer, KB Mason, RP TI ESR spin-trapping of a protein-derived tyrosyl radical from the reaction of cytochrome c with hydrogen peroxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIPID-PEROXIDATION; HYDROPEROXIDE; RESONANCE; METMYOGLOBIN; CATALASE; TYR-151; DAMAGE; HEART AB The reaction of horse heart cytochrome c with hydrogen peroxide was investigated using the ESR spin-trapping technique and the nitroso spin traps 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS) and 2-methyl-2-nitrosopropane (MNP). The ESR spectra obtained using both spin traps were typical of an immobilized nitroxide and indicated that the adduct was a macromolecule, The intensity of the ESR spectrum corresponding to the DBNBS/(.)cytochrome c radical adduct was greatly enhanced by performing the reaction under anaerobic conditions, which suggested that the spin trap was competing with O-2 for reaction with the radical site(s), Nonspecific proteolysis of either the DBNBS or the MNP adducts revealed isotropic three-line spectra, In addition, a high resolution ESR spectrum for the protease-treated MNP cytochrome c-derived protein radical adduct was obtained. The superhyperfine couplings detected in this spectra were identical to those detected from an authentic MNP/tyrosyl adduct, Carbon-13 labeling of the aromatic ring positions of tyrosine yielded additional hyperfine coupling, demonstrating that the radical site was definitely located on the ring of tyrosine, Mass spectrometry detected as many as four DBNBS/(.)cytochrome c-derived adducts from the reaction of cytochrome with H2O2, Thus, it would appear four radical sites are formed during the reaction, at least one of which is tyrosine. RP Barr, DP (reprint author), NIEHS,MOLEC BIOPHYS LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Tomer, Kenneth/E-8018-2013 NR 41 TC 120 Z9 122 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15498 EP 15503 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900031 PM 8663160 ER PT J AU Graham, C Hodin, J Wistow, G AF Graham, C Hodin, J Wistow, G TI A retinaldehyde dehydrogenase as a structural protein in a mammalian eye lens - Gene recruitment of eta-crystallin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOSOLIC ALDEHYDE DEHYDROGENASE; RETINOIC ACID; TRANSGENIC MICE; EXPRESSION; OXIDATION; SEQUENCE; CDNA AB eta-Crystallin is a taxon-specific crystallin, a major component of the eye lens in elephant shrews (Macroscelidea). Sequence analysis of eta-crystallin from two genera of elephant shrews and expression of recombinant eta-crystallin show that the protein is a cytoplasmic (class 1) aldehyde dehydrogenase (ALDH1, EC 1.2.1.3) with activity for the oxidation of retinaldehyde to retinoic acid. Unlike many other mammals, elephant shrews have two ALDH1 genes. One encodes ALDH1/eta-crystallin which, in addition to its very high expression in lens, is also the predominant form of ALDH1 expressed in other parts of the eye. The second gene encodes a ''non-lens'' ALDH1 (ALDH1-n1) which is the predominant form expressed in liver. This pattern of tissue preference contrasts with other mammals which make use of the same major ALDH1 transcript in both ocular and non-ocular tissues. Thus the gene recruitment of ALDH1/eta-crystallin as a structural protein in elephant shrew lenses is associated with its collateral recruitment as the major form of ALDH1 expressed in other parts of the eye. C1 NEI,SECT MOLEC STRUCT & FUNCT,LMDB,NIH,BETHESDA,MD 20892. NR 51 TC 44 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15623 EP 15628 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900049 PM 8663049 ER PT J AU Blahos, J Wenthold, RJ AF Blahos, J Wenthold, RJ TI Relationship between N-methyl-D-aspartate receptor NR1 splice variants and NR2 subunits SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NMDA-RECEPTOR; RAT-BRAIN; IMMUNOCYTOCHEMICAL LOCALIZATION; SYNAPTIC PLASTICITY; NERVOUS-SYSTEM; SOLUBILIZATION; POLYAMINES; INVITRO; CLONING AB The N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptor is assembled from one NR1 subunit, expressed in eight splice variants, and four NR2 subunits (NR2A-D). The combination of subunits and splice variants determines the pharmacological and physiological properties of the receptor. In the present study we investigated the relationship between NR1 splice variants and NR2 subunits in rat brain using a series of antibodies selective for the four NR1 cassettes, which vary in the NR1 splice variants, and for NR2A and NR2B. Sodium deoxycholate at pH 9.0 solubilized about 35% of the receptor, which was intact based on co-immunoprecipitation of NR1 and NR2 subunits and chemical cross-linking of the solubilized receptor. The crosslinked product contained three high molecular weight components, M(r) = 603,000, 700,000, and 750,000, which were immunolabeled with antibodies to NR1 and to NR2 subunits. Immunoprecipitation analyses using antibodies selective for NR2A and NR2B showed no preferential assembly between NR2 subunits and NR1 splice variants. There was little co-immunoprecipitation of NR2A and NR2B, suggesting that most NMDA receptor complexes contain only one of these subunits. However, receptor complexes can contain at least two different NR1 splice variants. In developing conditions for the solubilization of intact NMDA receptor complexes, we observed a differential solubilization of NR1 and NR2 subunits. NR2 was nearly insoluble in Triton X-100 in both microsomal and synaptic membrane fractions, while NR1 was readily soluble in the microsomal fraction but insoluble in the synaptic membrane fraction. These results suggest that the NR1 subunit is modified when it is incorporated into the synaptic membrane, possibly by strengthening its interaction with NR2 or another synaptic protein. C1 NIDCD,NIH,NEUROCHEM LAB,BETHESDA,MD 20892. RI Blahos, Jaroslav/G-4397-2014 NR 54 TC 128 Z9 130 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15669 EP 15674 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900056 PM 8663041 ER PT J AU Isakov, N Wange, RL Watts, JD Aebersold, R Samelson, LE AF Isakov, N Wange, RL Watts, JD Aebersold, R Samelson, LE TI Purification and characterization of human ZAP-70 protein-tyrosine kinase from a baculovirus expression system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; T-CELL; ZETA-CHAIN; CYTOPLASMIC DOMAIN; INITIAL CHARACTERIZATION; HUMAN PLATELETS; SH2 DOMAINS; ACTIVATION; P56LCK; ASSOCIATION AB The ZAP-70 protein tyrosine kinase is essential for T cell antigen receptor (TCR)-mediated signaling. The absence of ZAP-70 results in impaired differentiation of T cells and a lack of responsiveness to antigenic stimulation. In order to study the characteristics of ZAP-70 in vitro, we overexpressed an epitopically tagged human ZAP-70 in a recombinant baculovirus expression system and purified it by column chromatography. The kinase activity of purified, recombinant ZAP-70 required cation and exhibited a strong preference for Mn2+ over Mg2+. The apparent K-m of ZAP-70 for ATP was similar to 3.0 mu M. The activity of the recombinant ZAP-70, unlike that of the homologous protein tyrosine kinase, Syk, was not affected by binding of TCR-derived tyrosine phosphorylated immunoreceptor tyrosine-based activation motif peptides. Several proteins were tested as potential in vitro substrates of ZAP-70. Only alpha-tubulin and the cytoplasmic fragment of human erythrocyte band 3 (cfb3), which have a region of sequence identity at the phosphorylation site, proved to be good substrates, exhibiting K-m values of similar to 3.3 and similar to 2.5 mu M respectively ([ATP] = 50 mu M). alpha- and beta-Casein were poor substrates for ZAP-70, and no activity toward enolase, myelin basic protein, calmodulin, histone proteins, or angiotensin could be detected. In contrast to the T cell protein tyrosine kinase, Lck, ZAP-70 did not phosphorylate the cytoplasmic portion of the TCR zeta chain or short peptides corresponding to the CD3 epsilon or the TCR zeta immunoreceptor tyrosine-based activation motifs. Our studies suggest that ZAP-70 exhibits a high degree of substrate specificity. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,DEPT MICROBIOL & IMMUNOL,IL-84105 BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,CANC RES CTR,IL-84105 BEER SHEVA,ISRAEL. UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. RI ISAKOV, NOAH/F-1659-2012 NR 66 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15753 EP 15761 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900068 PM 8663155 ER PT J AU Zhu, YX Kang, LY Luo, W Li, CCH Yang, L Yang, YC AF Zhu, YX Kang, LY Luo, W Li, CCH Yang, L Yang, YC TI Multiple transcription factors are required for activation of human interleukin 9 gene in T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS FACTOR-ALPHA; NF-KAPPA-B; GROWTH-FACTOR; EXPRESSION; MURINE; ELEMENT; IDENTIFICATION; PROLIFERATION; LYMPHOCYTES; LYMPHOMAS AB The genetic elements and regulatory mechanisms responsible for human interleukin 9 (IL-9) gene expression in a human T cell leukemia virus type I-transformed human T cell line, C5MJ2, were investigated. We demonstrated that IL-9 gene expression is controlled, at least in part, by transcriptional activation. Transient expression of the luciferase reporter gene Linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells. An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene. A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells. Within this region, an NF-kappa B site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-kappa B, c-Jun, and potentially novel proteins (around 35 kDa) can bind to this important sequence. Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding. Taken together, these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells. C1 INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED HEMATOL ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,INDIANAPOLIS,IN 46202. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC,FREDERICK,MD. FU NHLBI NIH HHS [R01HL48819]; NIDDK NIH HHS [R01DK43105] NR 49 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 28 PY 1996 VL 271 IS 26 BP 15815 EP 15822 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV299 UT WOS:A1996UV29900077 PM 8663174 ER PT J AU Alkhatib, G Combadiere, C Broder, CC Feng, Y Kennedy, PE Murphy, PM Berger, EA AF Alkhatib, G Combadiere, C Broder, CC Feng, Y Kennedy, PE Murphy, PM Berger, EA TI CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1 SO SCIENCE LA English DT Article ID BACTERIOPHAGE-T7 RNA-POLYMERASE; IMMUNODEFICIENCY-VIRUS; CD4-MEDIATED FUSION; VACCINIA VIRUS; MURINE CELLS; EXPRESSION; INFECTION; SYSTEM; GENES; CD4 AB Human immunodeficiency virus-type 1 (HIV-1) entry requires fusion cofactors on the CD4(+) target cell. Fusin, a heterotrimeric GTP-binding protein (G protein)-coupled receptor, serves as a cofactor for T cell line-tropic isolates. The chemokines RANTES, MIP-1 alpha, and MIP-1 beta, which suppress infection by macrophage-tropic isolates, selectively inhibited cell fusion mediated by the corresponding envelope glycoproteins (Envs). Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs. CC CKR5 messenger RNA was detected selectively in cell types susceptible to macrophage-tropic isolates. CC CKR5 is thus a fusion cofactor for macrophage-tropic HIV-1 strains. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 32 TC 2212 Z9 2247 U1 7 U2 43 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 28 PY 1996 VL 272 IS 5270 BP 1955 EP 1958 DI 10.1126/science.272.5270.1955 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UV294 UT WOS:A1996UV29400054 PM 8658171 ER PT J AU Cuvillier, O Pirianov, G Kleuser, B Vanek, PG Coso, OA Gutkind, JS Spiegel, S AF Cuvillier, O Pirianov, G Kleuser, B Vanek, PG Coso, OA Gutkind, JS Spiegel, S TI Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate SO NATURE LA English DT Article ID PROLIFERATION AB CERAMIDE is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-alpha and Fas ligand, members of the TNF superfamily(1-6). Conversely, sphingosine and sphingosine-1-phosphate, which are metabolites of ceramide, induce mitogenesis(7) and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor and serum(8,9). Here we report that sphingosine-1-phosphate prevents the appearance of the key features of apoptosis, namely intranucleosomal DNA fragmentation and morphological changes, which result from increased concentrations of ceramide. Furthermore, inhibition of ceramide-mediated apoptosis by activation of protein kinase C results from stimulation of sphingosine kinase and the concomitant increase in intracellular sphingosine-l-phosphate. Finally sphingosine-1-phosphate not only stimulates the extracellular signal-regulated kinase (ERK) pathway(10), it counteracts the ceramide-induced activation of stress-activated protein kinase (SAPK/JNK). Thus, the balance between the intracellular levels of ceramide and sphingosine-1-phosphate and their regulatory effects on different family members of mitogen-activated protein kinases determines the fate of the cell. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. TREVIGEN INC,GAITHERSBURG,MD 20877. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009; CUVILLIER, Olivier/B-2567-2009 OI CUVILLIER, Olivier/0000-0003-3346-375X NR 30 TC 1041 Z9 1055 U1 3 U2 36 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 27 PY 1996 VL 381 IS 6585 BP 800 EP 803 DI 10.1038/381800a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU356 UT WOS:A1996UU35600064 PM 8657285 ER PT J AU ConryCantilena, C VanRaden, M Gibble, J Melpolder, J Shakil, AO Viladomiu, L Cheung, L DiBisceglie, A Hoofnagle, J Shih, JW Kaslow, R Ness, P Alter, HJ AF ConryCantilena, C VanRaden, M Gibble, J Melpolder, J Shakil, AO Viladomiu, L Cheung, L DiBisceglie, A Hoofnagle, J Shih, JW Kaslow, R Ness, P Alter, HJ TI Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NON-B-HEPATITIS; NON-A-HEPATITIS; UNITED-STATES; TRANSMISSION; RISK; ANTIBODIES AB Background. For many people infected with the hepatitis C virus (HCV), the route of exposure, risk of transmission, and severity of associated liver disease are unknown. We studied these variables in people who donated blood voluntarily. Methods. Blood donors who tested positive for HCV antibodies on enzyme immunoassay were classified according to whether the results of a confirmatory second-generation recombinant immunoblot assay (RIBA) for HCV were positive, negative, or indeterminate. The evaluations also included an assessment of risk factors, a physical examination, serial determinations of alanine aminotransferase levels and HCV serologic assays, a polymerase-chain-reaction assay for HCV RNA, testing of sexual contacts and family members, and liver biopsies in some participants who were HCV-positive by RIBA. Results. A total of 481 donors were studied, among whom 248 were positive for HCV by RIBA, 102 had indeterminate results, and 131 were HCV-negative. In a logistic-regression analysis, significant risk factors for HCV infection among the HCV-positive participants were a history of blood transfusion in 66 (27 percent; P<0.001 for the comparison with RIBA-negative donors), intranasal cocaine use in 169 (68 percent, P<0.001), intravenous drug use in 103 (42 percent, P=0.001), sexual promiscuity in 132 (53 percent, P= 0.002), and ear piercing among men (P<0.05). Nine of 85 sexual partners of HCV-positive donors were anti-HCV-positive; 8 had used intravenous drugs or received transfusions. HCV RNA was found in 213 HCV-positive donors (86 percent), 3 who had indeterminate results by RIBA (2 of these 3 tested positive with a more specific, third-generation RIBA), and none who were HCV-negative. Of the HCV-positive donors, 69 percent had biochemical evidence of chronic liver disease; among 77 donors positive for HCV by RIBA who underwent liver biopsy, 5 had severe chronic hepatitis or cirrhosis, 66 had mild-to-moderate chronic hepatitis, and 6 had no evidence of hepatitis. Conclusions. Among volunteer blood donors, prior blood transfusion, intranasal cocaine use, intravenous drug use, sexual promiscuity, and ear piercing in men are risk factors for HCV infection. The high frequency of intravenous drug use was unexpected, because these donors had denied such use when questioned directly at the time of their blood donations. (C) 1996, Massachusetts Medical Society. C1 NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD 20892. NIDDKD,NIH,BETHESDA,MD 20892. GREATER CHESAPEAKE & POTOMAC REG AMER RED CROSS,BALTIMORE,MD. HOSP GEN VALLE HEBRON,BARCELONA,SPAIN. ST LOUIS UNIV,HLTH SCI CTR,DEPT INTERNAL MED,ST LOUIS,MO 63103. RP ConryCantilena, C (reprint author), NIH,DEPT TRANSFUS MED,BLDG 10,RM 1C711,BETHESDA,MD 20892, USA. NR 33 TC 465 Z9 482 U1 2 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 27 PY 1996 VL 334 IS 26 BP 1691 EP 1696 DI 10.1056/NEJM199606273342602 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UT400 UT WOS:A1996UT40000002 PM 8637513 ER PT J AU Vincent, F Hagiwara, K Ke, Y Stoner, GD Demetrick, DJ Bennett, WP AF Vincent, F Hagiwara, K Ke, Y Stoner, GD Demetrick, DJ Bennett, WP TI Mutation analysis of the transforming growth factor beta type II receptor in sporadic human cancers of the pancreas, liver, and breast SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELL AB The transforming growth factor beta (TGFbeta) binds the type II TGFbeta growth factor receptor (TGFbeta RII) to inhibit growth of most epithelial tissues. Most human colon cancers with microsatellite instability have frameshift mutations in two microsatellites within the TGFbeta RII coding region; such mutations truncate the receptor to produce resistance to TGFbeta. To investigate this pathway in other tissues, we surveyed sporadic human cancers of the pancreas, liver and breast to determine the frequency of microsatellite mutations in the TGFbeta RII. We amplified genomic DNA segments containing two microsatellites plus 72% of domain XI of the serine-threonine kinase region. SSCP analysis showed no evidence of mutation in 32 sporadic cancers (12 pancreas, 10 liver, and 10 breast). We conclude that microsatellite mutations in TGFbeta RII are uncommon in sporadic tumors of the pancreas, liver and breast. (C) 1996 Academic Press, Inc. C1 NCI,NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. OHIO STATE UNIV,DEPT PREVENT MED,COLUMBUS,OH 43210. UNIV CALGARY,FAC MED,DEPT PATHOL,CALGARY,AB T2N 4N1,CANADA. NR 15 TC 57 Z9 58 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 1996 VL 223 IS 3 BP 561 EP 564 DI 10.1006/bbrc.1996.0934 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV152 UT WOS:A1996UV15200015 PM 8687435 ER PT J AU Cleaveland, ES Zaharevitz, DW Kelley, JA Paull, K Cooney, DA Ford, H AF Cleaveland, ES Zaharevitz, DW Kelley, JA Paull, K Cooney, DA Ford, H TI Identification of a novel inhibitor (NSC 665564) of dihydroorotate dehydrogenase with a potency equivalent to brequinar SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TUMOR-CELL-LINES; NUCLEOTIDE BIOSYNTHESIS; SODIUM; DRUGS AB A novel inhibitor of dihydroorotate dehydrogenase (DHO-DH) has been discovered using data from the National Cancer Institute's in vitro drug screen. Upon analysis of cytotoxicity results from the sixty tumor cell lines used in this screen. the COMPARE program predicted that NSC 665564 was likely to have the same mechanism of inhibition as brequinar, a known potent inhibitor of DHO-DH. We validated this prediction experimentally using MOLT-4 lymphoblast and found the IC50 of brequinar (0.5 mu M) and NSC 665564 (0.3 mu M) were comparable and that this induced cytotoxicity was reversed by either uridine or cytidine. The enzyme target of NSC 665564 was shown to be identical to that of brequinar when incubation with each drug followed by a 1 h pulse with [C-14] sodium bicarbonate resulted in cellular accumulation of [C-14]N-carbamyl-L-aspartic acid and [C-14]L-dihydroorotic acid, with concurrent marked depletion of CTP and UTP, The K-i's for NSC 665564 and brequinar were 0.14 and 0.24 mu M, respectively, when partially purified MOLT-4 mitochondria (the site of DHO-DH) were used. These results show that mechanistic predictions obtained using correlations from the COMPARE algorithm are independent of structure since the structure of NSC 665564 is dissimilar to that of other established DHO-DH inhibitors. (C) 1996 Academic Press, Inc. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,INFORMAT TECHNOL BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,NIH,ROCKVILLE,MD 20892. NR 16 TC 11 Z9 11 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 1996 VL 223 IS 3 BP 654 EP 659 DI 10.1006/bbrc.1996.0950 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV152 UT WOS:A1996UV15200031 PM 8687451 ER PT J AU Gao, JL Sen, AI Kitaura, M Yoshie, O Rothenberg, ME Murphy, PM Luster, AD AF Gao, JL Sen, AI Kitaura, M Yoshie, O Rothenberg, ME Murphy, PM Luster, AD TI Identification of a mouse eosinophil receptor for the CC chemokine eotaxin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article AB The CC chemokine eotaxin is a selective chemoattractant for eosinophils in vitro and induces eosinophil migration in vivo. Here we show that the mouse orphan receptor previously named macrophage inflammatory protein-1 alpha receptor-like 2 is a functional eotaxin receptor. For consistency with other nomenclature, we have renamed the receptor mouse CC chemokine receptor 3. Human and mouse eotaxin, but not other chemokines, induced transient increases in [Ca2+](i) in human embryonic kidney 293 cells expressing the receptor. RNA for the receptor was abundant in primary eosinophils, but at low levels in neutrophils and macrophages. These properties make this receptor the best known candidate to mediate mouse eosinophil responses to eotaxin. (C) 1996 Academic Press, Inc. C1 SHIONOGI INST MED SCI,OSAKA 566,JAPAN. HARVARD UNIV,SCH MED,DEPT GENET,HOWARD HUGHES MED INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. RP Gao, JL (reprint author), NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892, USA. NR 14 TC 66 Z9 66 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 1996 VL 223 IS 3 BP 679 EP 684 DI 10.1006/bbrc.1996.0955 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV152 UT WOS:A1996UV15200036 PM 8687456 ER PT J AU Liu, JM Poiley, J Devetten, M Kajigaya, S Walsh, CE AF Liu, JM Poiley, J Devetten, M Kajigaya, S Walsh, CE TI The Fanconi anemia complementation group C gene (FAG) suppresses transformation of mutant fibroblasts by the SV40 virus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEINS; DELAY; CELLS; FACC AB Fanconi anemia (FA) is a heterogeneous genetic syndrome manifested by bone marrow failure and consisting of at least five complementation groups (A, B, C, D, E). Mutations in a gene termed FAC are responsible for the C complementation group, but the function of the FAG protein remains obscure. FA patients are also highly cancer-prone; the molecular basis for this susceptibility is unclear but has led to the hypothesis that the wild-type FA gene may act as a tumor suppressor. In vitro, mutant FA primary fibroblasts are 3- to 50-fold more sensitive than normal fibroblasts to transformation in culture by the SV40 virus. We confirmed this marked susceptibility to transformation of a FAG-mutant primary fibroblast cell line, GM449. We then introduced a copy of the wild-type FAC cDNA into GM449 cells using a recombinant adeno-associated virus (rAAV) vector. We found that GM449 cells transduced with a copy of the normal FAC cDNA by a FAC-rAAV vector were at least 10-fold less prone to form transformed foci. Diminished transformation potential of transduced cells was a specific effect of the FAC cDNA since GM449 cells transduced with a rAAV vector not containing FAC retained marked susceptibility to SV40 transformation. (C) 1996 Academic Press, Inc. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIH,CPD,SERV HEMATOL,BETHESDA,MD 20892. BIOL RES FAC & FACIL INC,IJAMSVILLE,MD. NR 27 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 1996 VL 223 IS 3 BP 685 EP 690 DI 10.1006/bbrc.1996.0956 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV152 UT WOS:A1996UV15200037 PM 8687457 ER PT J AU Trisler, D Rutin, J Pessac, B AF Trisler, D Rutin, J Pessac, B TI Retinal engineering: Engrafted neural cell lines locate in appropriate layers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE central nervous system; transplantation; cell migration and differentiation; cell recognition; pattern formation ID ROUS-SARCOMA VIRUS; CULTURES; MARKERS; ORIGIN AB A major question in central nervous system development, including the neuroretina, is whether migrating cells express cues to find their way and settle at specific locations. We have transplanted quail neuroretinal cell lines QNR/D, a putative amacrine or ganglion cell, and QNR/K2, a putative Muller cell into chicken embryo eyes, Implanted QNR/D cells migrate only to the retinal ganglion and amacrine cell layers and project neurites in the plane of retina; in contrast, QNR/K2 cells migrate through the ganglion and amacrine layers, locate in the inner nuclear layer, and project processes across the retina, These data show that QNR/D and QNR/K2 cell lines represent distinct neural cell types, suggesting that migrating neural cells express distinct address cues, Furthermore, our results raise the possibility that immortalized cell lines can be used for replacement of specific cell types and for the transport of genes to given locations in neuroretina. C1 UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. CNRS,UNITE PROPRE RECH 9035,F-75270 PARIS 06,FRANCE. RP Trisler, D (reprint author), NHLBI,NIH,LAB BIOCHEM GENET,BETHESDA,MD 20850, USA. NR 18 TC 14 Z9 14 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6269 EP 6274 DI 10.1073/pnas.93.13.6269 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700011 PM 8692804 ER PT J AU McCall, MA Gregg, RG Behringer, RR Brenner, M Delaney, CL Galbreath, EJ Zhang, CL Pearce, RA Chiu, SY Messing, A AF McCall, MA Gregg, RG Behringer, RR Brenner, M Delaney, CL Galbreath, EJ Zhang, CL Pearce, RA Chiu, SY Messing, A TI Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE long-term potentiation; hippocampus; optic nerve; homologous recombination; mouse ID FIBRILLARY ACIDIC PROTEIN; LONG-TERM POTENTIATION; SCHWANN-CELLS; REACTIVE ASTROCYTES; EXPRESSION; VIMENTIN; BRAIN; TRANSITION; NERVES; GROWTH AB Glial fibrillary acidic protein (GFAP) is a member of the family of intermediate filament structural proteins and is found predominantly in astrocytes of the central nervous system (CNS), To assess the function of GFAP, we created GFAP-null mice using gene targeting in embryonic stem cells, The GFAP-null mice have normal development and fertility, and show no gross alterations in behavior or CNS morphology, Astrocytes are present in the CNS of the mutant mice, but contain a severely reduced number of intermediate filaments, Since astrocyte processes contact synapses and may modulate synaptic function, we examined whether the GFAP-null mice were altered in long-term potentiation in the CAI region of the hippocampus. The GFAP-null mice displayed enhanced long-term potentiation of both population spike amplitude and excitatory post-synaptic potential slope compared to control mice, These data suggest that GFAP is important for astrocyte-neuronal interactions, and that astrocyte processes play a vital role in modulating synaptic efficacy in the CNS. These mice therefore represent a direct demonstration that a primary defect in astrocytes influences neuronal physiology. C1 UNIV WISCONSIN,DEPT ANESTHESIOL ANAT,MADISON,WI 53706. UNIV WISCONSIN,DEPT NEUROPHYSIOL,MADISON,WI 53706. UNIV WISCONSIN,NEUROSCI TRAINING PROGRAM,MADISON,WI 53706. UNIV WISCONSIN,WAISMAN CTR,MADISON,WI 53706. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX 77030. NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. RP McCall, MA (reprint author), UNIV WISCONSIN,SCH VET MED,DEPT PATHOBIOL SCI,2015 LINDEN DR,MADISON,WI 53706, USA. OI McCall, Maureen/0000-0002-9781-315X NR 47 TC 227 Z9 232 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6361 EP 6366 DI 10.1073/pnas.93.13.6361 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700027 PM 8692820 ER PT J AU Lan, MS Wasserfall, C Maclaren, NK Notkins, AL AF Lan, MS Wasserfall, C Maclaren, NK Notkins, AL TI IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoantibodies ID GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIBODIES; AUTOANTIBODIES; ANTIGEN; IDENTIFICATION; ONSET AB IA-2 is a 105,847 Da transmembrane protein that belongs to the protein tyrosine phosphatase family, Immunoperoxidase staining with antibody raised against IA-2 showed that this protein Is expressed in human pancreatic islet cells, In this study, we expressed the full-length cDNA clone of IA-2 in a rabbit reticulocyte transcription/translation system and used the recombinant radiolabeled IA-2 protein to detect autoantibodies by immunoprecipitation, Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls, Sixty-six percent of the sera from patients, but none of the sera from controls, reacted with IA-2, The same diabetic sera tested for autoantibodies to islet cells (ICA) by indirect immunofluorescence and glutamic acid decarboxylase (GAD(65)Ab) by depletion ELISA showed 68% and 52% positivity, respectively, Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD(65). Moreover, greater than 90% (14 of 15) of the ICA-positive but GAD(65) Ab-negative sera had autoantibodies to IA-2, Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD(65) when the respective antibody was present, A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD(65), arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD(65) If is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD(65), is responsible for much of the reactivity of ICA with pancreatic islets, Tests for the detection of autoantibodies to recombinant IA-2 and GAD(65) may eventually replace ICA immunofluorescence for IDDM population screening. C1 UNIV FLORIDA,COLL MED,DEPT PATHOL & LAB MED,GAINESVILLE,FL 32610. RP Lan, MS (reprint author), NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [GGRC MO1 RR00082]; NICHD NIH HHS [R01 HD19469]; NIDDK NIH HHS [P01 DK39079] NR 26 TC 171 Z9 177 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6367 EP 6370 DI 10.1073/pnas.93.13.6367 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700028 PM 8692821 ER PT J AU Emiliani, S VanLint, C Fischle, W Paras, P Ott, M Brady, J Verdin, E AF Emiliani, S VanLint, C Fischle, W Paras, P Ott, M Brady, J Verdin, E TI A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; T-CELL CLONE; NF-KAPPA-B; PERIPHERAL-BLOOD; INSITU HYBRIDIZATION; GENE-EXPRESSION; MESSENGER-RNA; TYPE-1; PROTEIN AB Study of the mechanism of HIV-1 postintegration latency in the ACH2 cell line demonstrates that these cells failed to Increase HIV-1 production following treatment with exogenous Tat, Reasoning that the defect in ACH2 cells involves the Tat response, we analyzed the sequence of tat cDNA and Tat responsive element (TAR) from the virus integrated in ACH2. Tat cDNA sequence is closely related to that of HIVLAI, and the encoded protein is fully functional in terms of long terminal repeat (LTR) transactivation, Cloning of a region corresponding to the 5'-LTR from ACH2, however, identified a point mutation (C-37-->T) in TAR. This mutation impaired Tat responsiveness of the LTR in transient transfection assays, and the measured defect was complemented in cells that had been treated with tetradecanoyl phorbol acetate or tumor necrosis factor type alpha (TNF-alpha). A compensatory mutation in TAR (G(28) --> A), designed to reestablish base pairing in the TAR hairpin, restored wild-type Tat responsiveness. When the (C-37 --> T) mutation was introduced in an infectious clone of HIV-1, no viral production was measured in the absence of TNF-alpha, whereas full complementation was observed when the infection was conducted in the presence of TNF-alpha or when a compensatory mutation (G(28) --> A) was introduced into TAR, These experiments identify a novel mutation associated with HIV-1 latency and suggest that alterations in the Tat-TAR axis can be a crucial determinant of the latent phenotype in infected individuals. C1 NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,NIH,BETHESDA,MD 20892. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RP Emiliani, S (reprint author), PICOWER INST MED RES,350 COMMUNITY DR,MANHASSET,NY 11030, USA. OI Ott, Melanie/0000-0002-5697-1274; Verdin, Eric/0000-0003-3703-3183 FU NIGMS NIH HHS [GM51671-01A1] NR 40 TC 102 Z9 105 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6377 EP 6381 DI 10.1073/pnas.93.13.6377 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700030 PM 8692823 ER PT J AU Bernstein, SL Kempner, E AF Bernstein, SL Kempner, E TI Radiation target analysis of RNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hammerhead ribozymes; molecular biology; molecular mass analysis ID RIBOZYMES; EVOLUTION; SEQUENCE AB Ribozymes are polynucleotide molecules with intrinsic catalytic activity, capable of cleaving nucleic acid substrates. Large RNA molecules were synthesized containing a hammerhead ribozyme moiety of 52 nucleotides linked to an inactive leader sequence, for total lengths of Either 262 or 1226 nucleotides. Frozen RNAs were irradiated with high energy electrons, Surviving ribozyme activity was determined using the ability of the irradiated ribozymes to cleave a labeled substrate. The amount of intact RNA remaining was determined from the same irradiated samples by scanning the RNA band following denaturing gel electrophoresis. Radiation target analyses of these data revealed a structural target size of 80 kDa and a ribozyme activity target size of 15 kDa for the smaller ribozyme, and 319 kDa and 16 kDa, respectively, for the larger ribozyme. The disparity in target size for activity versus structure indicates that, in contrast to proteins, there is no spread of radiation damage far from the primary site of ionization in RNA molecules, The smaller target size for activity indicates that only primary ionizations occurring in the specific active region are effective, This is similar to the ease for oligosaccharides. Wt concluded that the presence of the ribose sugar in the polymer chain restricts radiation damage to a small region and prevents major energy transfer throughout the molecule, Radiation target analysis should be a useful technique for evaluating local RNA:RNA and RNA:protein interactions in vitro. C1 NEI,NIH,BETHESDA,MD 20892. RP Bernstein, SL (reprint author), NIAMSD,NIH,ROOM 120,BLDG 6,BETHESDA,MD 20892, USA. NR 23 TC 9 Z9 9 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6410 EP 6414 DI 10.1073/pnas.93.13.6410 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700036 ER PT J AU Reardon, JT Ge, H Gibbs, E Sancar, A Hurwitz, J Pan, ZQ AF Reardon, JT Ge, H Gibbs, E Sancar, A Hurwitz, J Pan, ZQ TI Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transcription; DNA repair; cell cycle regulation ID DNA; PHOSPHORYLATION; ACTIVATION AB Transcription factor IIH (TFIIH) is a multisubunit protein complex essential for both the initiation of RNA polymerase class II (pol II)-catalyzed transcription and nucleotide excision repair of DNA. Recent studies have shown that TFIIH copurifies with the cyclin-dependent kinase (cdk)-activating kinase complex (CAK) that includes cdk7, cyclin H, and p36/MAT1. Here we report the isolation of two TFIIH-related complexes: TFIIH* and ERCC2/CAK. TFIIH* consists of a subset of the TFIIH complex proteins including ERCC2 (XPD), p62, p44, p41, and p34 but is devoid of detectable levels of ERCC2 (XPD) and CAK. ERCC2/CAK was isolated as a complex that exhibits CAK activity that cosediments with the three CAK components (cdk7, cyclin H, and p36/MAT1) as well as the ERCC2 (XPD) protein, TFIIH* can support pol II-catalyzed transcription in vitro with lower efficiency compared with TFIIH. This TFIIH*-dependent transcription reaction was stimulated by ERCC2/CAK. The ERCC2/CAK and TFIIH* complexes are each active in DNA repair as shown by their ability to complement extracts prepared from ERCC2 (XPD)- and ERCC3 (XPB)-deficient cells, respectively, in supporting the excision of DNA containing a cholesterol lesion. These data suggest that TFIIH* and ERCC2/CAK interact to form the TFIIH holoenzyme capable of efficiently assembling the pol II transcription initiation complex and directly participating in excision repair reactions. C1 UNIV N CAROLINA,SCH MED,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. NICHHD,MOLEC EMBRYOL LAB,NIH,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,GRAD PROGRAM MOL BIOL,NEW YORK,NY 10021. RP Reardon, JT (reprint author), MT SINAI MED CTR,DERALD H RUTTENBERG CANC CTR,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. FU NIGMS NIH HHS [GM32833, GM38559] NR 32 TC 95 Z9 96 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 JUN 25 PY 1996 VL 93 IS 13 BP 6482 EP 6487 DI 10.1073/pnas.93.13.6482 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700049 PM 8692841 ER PT J AU Zhao, TM Robinson, MA Bowers, FS Kindt, TJ AF Zhao, TM Robinson, MA Bowers, FS Kindt, TJ TI Infectivity of chimeric human T-cell leukemia virus type I molecular clones assessed by naked DNA inoculation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE human T-cell leukemia virus type I rex gene; cloned retrovirus; quantitative competitive-PCR ID TROPICAL SPASTIC PARAPARESIS; HTLV; RETROVIRUS; MYELOPATHY; PARTICLES; SELECTION; PATIENT; DISEASE; RABBITS AB Two human T-cell leukemia virus type I (HTLV-I) molecular clones, K30p and K34p were derived from HTLV-I-infected rabbit cell lines, K30p and K34p differ by 18 bp with changes in the long terminal repeats (LTRs) as well as in the gag, pol, and rex but not tax or env gene products, Cells transfected with clone K30p were infectious in vitro and injection of the K30p transfectants or naked K30p DNA into rabbits leads to chronic infection, In contrast, K34p did not mediate infection in vitro or in vitro, although the cell line from which it was derived is fully infectious and K34p transfectants produce intact virus particles. To localize differences involved in the ability of the clones to cause infection, six chimeric HTLV-I clones were constructed by shuffling corresponding fragments containing the substitutions in the LTRs, the gag/pol region and the rex region between K30p and K34p. Cells transfected with any of the sis chimeras produced virus, but higher levels of virus were produced by cells transfected with those constructs containing the K30p rex region, Virus production was transient except In cells transfected with K30p or with a chimera consisting of the entire protein coding region of K30p flanked by K34p LTRs; only the transfectants showing persistent virus production mediated in vitro infection, in vivo infection in rabbits following intramuscular DNA injection was mediated by K30p as well as by a chimera of K30p containing the K34p rex gene, Comparisons revealed that virus production was greater and appeared earlier in rabbits injected with K30p. These data suggest that several defects in the K34p clone preclude infectivity and furthermore, provide systems to explore functions of HTLV-I genes. C1 NIAID,IMMUNOGENET LAB,NIH,TWINBROOK FACIL 2,ROCKVILLE,MD 20852. NR 28 TC 14 Z9 14 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 JUN 25 PY 1996 VL 93 IS 13 BP 6653 EP 6658 DI 10.1073/pnas.93.13.6653 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700081 PM 8692873 ER PT J AU Kelly, JF Furukawa, K Barger, SW Rengen, MR Mark, RJ Blanc, EM Roth, GS Mattson, MP AF Kelly, JF Furukawa, K Barger, SW Rengen, MR Mark, RJ Blanc, EM Roth, GS Mattson, MP TI Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acetylcholine; Alzheimer disease; antioxidant; calcium; carbachol ID POSTMORTEM HUMAN-BRAIN; ALZHEIMERS-DISEASE; G-PROTEIN; RECEPTORS; PRECURSOR; RAT; HIPPOCAMPUS; MEMBRANES; BINDING; CYCLASE AB Cholinergic pathways serve important functions in learning and memory processes, and deficits in cholinergic transmission occur in Alzheimer disease (AD). A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C, resulting in the liberation of inositol trisphosphate and Ca2+ release from intracellular stores, We now report that amyloid beta-peptide (A beta), which forms plaques in the brain in AD, impairs muscarinic receptor activation of C proteins in cultured rat cortical neurons, Exposure of rodent fetal cortical neurons to A beta 25-35 and A beta L-40 resulted in a concentration and time-dependent attenuation of Carbachol-induced GTPase activity without affecting muscarinic receptor ligand binding parameters, Downstream events in the signal transduction cascade were similarly attenuated by A beta. Carbachol-induced accumulation of inositol phosphates (IP, IP2, IP3, and IP4) was decreased and calcium imaging studies revealed that carbachol-induced release of calcium was severely impaired in neurons pretreated with A beta. Muscarinic cholinergic signal transduction was disrupted with subtoxic levels of exposure to A beta. The effects of A beta on carbachol-induced GTPase activity and calcium release were attenuated by antioxidants, implicating free radicals in the mechanism whereby A beta induced uncoupling of muscarinic receptors, These data demonstrate that A beta disrupts muscarinic receptor coupling to G proteins that mediate induction of phosphoinositide accumulation and calcium release, findings that implicate A beta in the impairment of cholinergic transmission that occurs in AD. C1 UNIV KENTUCKY,DEPT ANAT & NEUROBIOL,LEXINGTON,KY 40536. NIA,MOLEC PHYSIOL & GENET SECT,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Kelly, JF (reprint author), UNIV KENTUCKY,SANDERS BROWN RES CTR AGING,211 SANDERS BROWN BLDG,LEXINGTON,KY 40536, USA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG10836]; NINDS NIH HHS [NS30538] NR 54 TC 172 Z9 178 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 25 PY 1996 VL 93 IS 13 BP 6753 EP 6758 DI 10.1073/pnas.93.13.6753 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UU367 UT WOS:A1996UU36700099 PM 8692890 ER PT J AU Lawrence, CW Borden, A Woodgate, R AF Lawrence, CW Borden, A Woodgate, R TI Analysis of the mutagenic properties of the UmuDC, MucAB and RumAB proteins, using a site-specific abasic lesion SO MOLECULAR & GENERAL GENETICS LA English DT Article DE Escherichia coli; umuDC; mucAB; rumAB; specifically located abasic site ID DNA POLYMERASE-III; ESCHERICHIA-COLI; RECA PROTEIN; MUTATION; LIGHT; SPECTRUM; HOMOLOGY; PLASMIDS; SUBUNIT; PKM101 AB The mucAB and rumAB loci have been shown to promote mutagenesis to a greater extent than the structurally and functionally homologous Escherichia coli umuDC operon. We have analyzed the basis of this enhanced mutagenesis by comparing the influence of these operons, relative to umuDC, on the mutagenic properties of each of two abasic sites, specifically located in a single-stranded vector. Experiments with these vectors are useful analytical tools because they provide independent estimates of the efficiency of translesion synthesis and of the relative frequencies of each type of nucleotide insertion or other kind of mutagenic event. The umuDC, mucAB, and rumAB genes were expressed from their natural LexA-regulated promoter on low-copy-number plasmids in isogenic strains carrying a umuDC deletion. In addition, plasmids expressing the UmuD'C, MucA'B, or RumA'B proteins were also used. Compared to umuDC, the chief effect of mucAB was to increase the efficiency of translesion synthesis past the abasic site. The enhanced capacity of mucAB for translesion synthesis depended about equally on an inherently greater capacity to promote this process and on a greater susceptibility of the MucA protein to proteolytic processing. The RumA protein also appeared to be more susceptible to proteolytic processing, but the inherent capacity of the Rum products for translesion synthesis was no greater than that of UmuDC. dAMP was inserted opposite one of the two abasic sites studied at a somewhat greater frequency in strains expressing rum (82%) compared to those expressing umu (72%), which might result in higher mutation frequencies in rumAB than in umuDC strains. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. RP Lawrence, CW (reprint author), UNIV ROCHESTER,MED CTR,DEPT BIOPHYS,ROCHESTER,NY 14642, USA. FU NIGMS NIH HHS [GM32885] NR 26 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JUN 24 PY 1996 VL 251 IS 4 BP 493 EP 498 DI 10.1007/BF02172378 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UV724 UT WOS:A1996UV72400012 PM 8709953 ER PT J AU Narayan, KMV Chadha, SL Hanson, RL Tandon, R Shekhawat, S Fernandes, RJ Gopinath, N AF Narayan, KMV Chadha, SL Hanson, RL Tandon, R Shekhawat, S Fernandes, RJ Gopinath, N TI Prevalence and patterns of smoking in Delhi: Cross sectional study SO BRITISH MEDICAL JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; CIGARETTE-SMOKING; INDIA; ACCULTURATION; POPULATION; HISPANICS AB Objective-To determine the prevalence and predictors of smoking in urban India. Design-Cross sectional. Setting-Delhi, urban India, 1985-6. Subjects-Random sample of 13 558 men and women aged 25-64 years. Main outcome measure-Smoking prevalence; subjects who were currently smoking and who had smoked. greater than or equal to 100 cigarettes or beedis or chuttas in their lifetime were defined as smokers. Results-45% (95% confidence interval 43.8 to 46.2) of men and 7% (6.4 to 7.6) of women were smokers. Education was the strongest predictor of smoking, and men with no education were 1.8 (1.5 to 2.0) times more likely to be smokers than those with college education, and women with no education were 3.7 (2.9 to 4.8) times more likely, Among smokers, 52.6% of men and 4.9% of women smoked only cigarettes white the others also smoked beedi or chutta. Compared with cigarette smokers, people smoking beedi or chutta were more likely to be older and married; have lower education, manual occupations, incomes, and body mass index; and not drink alcohol or take part in leisure exercise. Conclusion-There are two subpopulations of smokers in urban India, and the prevention strategy required for each may be different, The educated, white collar cigarette smoker in India might respond to measures that make nonsmoking fashionable, while the less educated, low income people who smoke beedi or chutta may need strategies aimed at socioeconomic improvement. C1 SITARAM BHARTIA INST SCI & RES,NEW DELHI 16,INDIA. RP Narayan, KMV (reprint author), NIDDKD,DIABETES & ARTHRITIS EPIDEMIOL SECT,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014, USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 27 TC 34 Z9 35 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUN 22 PY 1996 VL 312 IS 7046 BP 1576 EP 1579 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UU806 UT WOS:A1996UU80600019 PM 8664667 ER PT J AU Calle, EE Heath, CW MiracleMcMahill, HL Coates, RJ Liff, JM Franceschi, S Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Morabia, A Schuman, L Stewart, W Szklo, M Bain, C Schofield, F Siskind, V Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Duffy, SW Kolonel, LM Nomura, AMY Oberle, MW Ory, HW Peterson, HB Wilson, HG Wingo, PA Ebeling, K Kunde, D Nishan, P Colditz, G Martin, N Pardthaisong, T Silpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C McMichael, AJ Rohan, T Ewertz, M Paul, C Skegg, DCG Boyle, P Evstifeeva, M Daling, JR Malone, K Noonan, EA Stanford, JL Thomas, DB Weiss, NS White, E Andrieu, N Bremond, A Clavel, F Gairard, B Lansac, J Piana, L Renaud, R Cuevas, HR Ontiveros, P Palet, A Salazar, SB Aristizabel, N Cuadros, A Bachelot, A Le, MG Deacon, J Peto, J Taylor, CN Alfandary, E Modan, B Ron, E Friedman, GD Hiatt, RA Bishop, T Kosmelj, J PrimicZakelj, M Ravnihar, B Stare, J Beeson, WL Fraser, G Allen, DS Bulbrook, RD Cuzick, J Fentiman, IS Hayward, JL Wang, DY Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AO Weinstein, AL Moller, TR Olsson, H Ranstam, J Goldbohm, RA vandenBrandt, PA Apelo, RA Baens, J delaCruz, JR Javier, B Lacaya, LB Ngelangel, CA LaVecchia, C Negri, E Marubini, E Ferraroni, M Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Hoover, R Schairer, C Spirtas, R Lee, HP Rookus, MA vanLeeuwen, FE Schoenberg, JA Gammon, MD Clarke, EA Jones, L McPherson, K Neil, A Vessey, M Yeates, D Beral, V Bull, D Crossley, B Hermon, C Jones, S Key, T Lewis, C Reeves, G Smith, P Collins, R Doll, R Peto, R Hannaford, P Kay, C RoseroBixby, L Gao, YT Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Booth, JC Jelihovsky, T MacLennan, R Shearman, R Wang, QS Baines, CJ Miller, AB Wall, C Lund, E Stalsberg, H Dabancens, A Martinez, L Molina, R Salas, O Alexander, FE Hulka, BS Bernstein, L Haile, RW PaganiniHill, A Pike, MC Ross, RK Ursin, G Yu, MC Adami, HO Bergstrom, R Longnecker, MP Newcomb, P Farley, TMN Holck, S Meirik, O AF Calle, EE Heath, CW MiracleMcMahill, HL Coates, RJ Liff, JM Franceschi, S Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Morabia, A Schuman, L Stewart, W Szklo, M Bain, C Schofield, F Siskind, V Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Duffy, SW Kolonel, LM Nomura, AMY Oberle, MW Ory, HW Peterson, HB Wilson, HG Wingo, PA Ebeling, K Kunde, D Nishan, P Colditz, G Martin, N Pardthaisong, T Silpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C McMichael, AJ Rohan, T Ewertz, M Paul, C Skegg, DCG Boyle, P Evstifeeva, M Daling, JR Malone, K Noonan, EA Stanford, JL Thomas, DB Weiss, NS White, E Andrieu, N Bremond, A Clavel, F Gairard, B Lansac, J Piana, L Renaud, R Cuevas, HR Ontiveros, P Palet, A Salazar, SB Aristizabel, N Cuadros, A Bachelot, A Le, MG Deacon, J Peto, J Taylor, CN Alfandary, E Modan, B Ron, E Friedman, GD Hiatt, RA Bishop, T Kosmelj, J PrimicZakelj, M Ravnihar, B Stare, J Beeson, WL Fraser, G Allen, DS Bulbrook, RD Cuzick, J Fentiman, IS Hayward, JL Wang, DY Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AO Weinstein, AL Moller, TR Olsson, H Ranstam, J Goldbohm, RA vandenBrandt, PA Apelo, RA Baens, J delaCruz, JR Javier, B Lacaya, LB Ngelangel, CA LaVecchia, C Negri, E Marubini, E Ferraroni, M Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Hoover, R Schairer, C Spirtas, R Lee, HP Rookus, MA vanLeeuwen, FE Schoenberg, JA Gammon, MD Clarke, EA Jones, L McPherson, K Neil, A Vessey, M Yeates, D Beral, V Bull, D Crossley, B Hermon, C Jones, S Key, T Lewis, C Reeves, G Smith, P Collins, R Doll, R Peto, R Hannaford, P Kay, C RoseroBixby, L Gao, YT Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Booth, JC Jelihovsky, T MacLennan, R Shearman, R Wang, QS Baines, CJ Miller, AB Wall, C Lund, E Stalsberg, H Dabancens, A Martinez, L Molina, R Salas, O Alexander, FE Hulka, BS Bernstein, L Haile, RW PaganiniHill, A Pike, MC Ross, RK Ursin, G Yu, MC Adami, HO Bergstrom, R Longnecker, MP Newcomb, P Farley, TMN Holck, S Meirik, O CA Collaborative Group on Hormonal Factors in Breast Cancer TI Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53297 women with breast cancer and 100239 women without breast cancer from 54 epidemiological studies SO LANCET LA English DT Article ID ORAL-CONTRACEPTIVES; RISK-FACTORS; PREMENOPAUSAL WOMEN; FINAL REPORT; YOUNG-WOMEN; AGE; POPULATION; ESTROGEN; ASSOCIATION; PATTERNS AB Background The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. Methods Individual data on 53297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. Findings The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95% CI] in current users 1.24 [1.15-1.33], 2p<0.00001; 1-4 years after stopping 1.16 [1.08-1.23], 2p=0.00001; 5-9 years after stopping 1.07 [1.02-1.13], 2p=0.009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1.01 [0.96-1.05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives: for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0.88 (0.81-0.95; 2p=0.002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90% of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0.5 (95% CI 0.3-0.7), 1.5 (0.7-2.3), and 4.7 (2.7-6.7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons. Interpretation Women who are currently using combined oral contraceptives or have used them in the past 10 years are at a slightly increased risk of having breast cancer diagnosed, although the additional cancers diagnosed tend to be localised to the breast. There is no evidence of an increase in the risk of having breast cancer diagnosed 10 or more years after cessation of use, and the cancers diagnosed then are less advanced clinically than the cancers diagnosed in never-users. C1 AMER CANC SOC, NEW YORK, NY USA. EMORY UNIV, ATLANTA, GA 30322 USA. AVIANO CANC CTR, PORDENONE, ITALY. MAHIDOL UNIV, BANGKOK 10700, THAILAND. JOHNS HOPKINS UNIV, BREAST TUMOR COLLABORAT STUDY, BALTIMORE, MD 21218 USA. UNIV QUEENSLAND, ST LUCIA, QLD 4067, AUSTRALIA. BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC V5Z 4E6, CANADA. MRC, BIOSTAT UNIT, LONDON W1N 4AL, ENGLAND. UNIV HAWAII, CANC RES CTR, HONOLULU, HI 96822 USA. CTR DIS CONTROL & PREVENT, ATLANTA, GA 30341 USA. CENT INST CANC RES, BERLIN, GERMANY. HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,CHANNING LAB, G COLDITZ NURSES HLTH STUDY RES GRP, CAMBRIDGE, MA 02138 USA. CHIANG MAI UNIV, CHIANG MAI 50000, THAILAND. CHULALONGKORN UNIV, BANGKOK 10330, THAILAND. CSIRO, DIV HUMAN NUTR, ADELAIDE, SA 5000, AUSTRALIA. DANISH CANC SOC, COPENHAGEN, DENMARK. UNIV OTAGO, DUNEDIN, NEW ZEALAND. EUROPEAN INST ONCOL, MILAN, ITALY. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. INSERM, FRENCH MULTICTR BREAST STUDY, PARIS, FRANCE. HOSP GEN MEXICO CITY, MEXICO CITY, DF, MEXICO. INST GUSTAVE ROUSSY, INSERM, F-94805 VILLEJUIF, FRANCE. INST CANC RES, SUTTON, SURREY, ENGLAND. ISRAEL CHAIM SHEBA MED CTR, TEL HASHOMER, ISRAEL. KAISER PERMANENTE, OAKLAND, CA 94612 USA. IMPERIAL CANC RES FUND, GENET EPIDEMIOL LAB, LONDON, ENGLAND. INST ONCOL, LJUBLJANA, SLOVENIA. LOMA LINDA UNIV, LOMA LINDA, CA 92350 USA. LONG ISL BREAST CANC STUDY, LONG ISL CITY, NY USA. UNIV LUND HOSP, S-22185 LUND, SWEDEN. UNIV LIMBURG, 6200 MD MAASTRICHT, NETHERLANDS. UNIV PHILIPPINES, MANILA, PHILIPPINES. IST MARIO NEGRI, MILAN, ITALY. IST NAZL TUMORI, DIV STAT MED & BIOMETRIA, MILAN, ITALY. MONTPELLIER CANC CTR, MONTPELLIER, FRANCE. INSERM, MONTPELLIER, FRANCE. NAIROBI CTR RES REPROD, NAIROBI, KENYA. NCI, BETHESDA, MD 20892 USA. NICHHD, BETHESDA, MD 20892 USA. NATL UNIV SINGAPORE, SINGAPORE 117548, SINGAPORE. NEW JERSEY STATE DEPT HLTH, TRENTON, NJ 08625 USA. COLUMBIA UNIV, SCH PUBL HLTH, NEW YORK, NY 10027 USA. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. UNIV OXFORD, DEPT PUBL HLTH & PRIMARY CARE, OXFORD OX3 7LF, ENGLAND. ROYAL COLL GEN PRACTITIONERS ORAL CONTRACEPT STUD, LONDON, ENGLAND. UNIV COSTA RICA, SAN JOSE, COSTA RICA. IMPERIAL CANC RES FUND, MRC, BHF, CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. IMPERIAL CANC RES FUND, MRC, BHF, EPIDEMIOL STUDIES UNIT, OXFORD, ENGLAND. SHANGHAI CANC INST, SHANGHAI, PEOPLES R CHINA. SHANGHAI INST PLANNED PARENTHOOD RES, SHANGHAI, PEOPLES R CHINA. DEPT PUBL HLTH, SIDNEY, BC, CANADA. TIANJIN CANC INST, TIANJIN, PEOPLES R CHINA. UNIV TORONTO, DEPT PREVENT MED & BIOSTAT, TORONTO, ON, CANADA. UNIV TROMSO, TROMSO, NORWAY. UNIV CHILE, SANTIAGO, CHILE. UNIV EDINBURGH, EDINBURGH, MIDLOTHIAN, SCOTLAND. UNIV N CAROLINA, SCH PUBL HLTH, CHAPEL HILL, NC USA. UNIV NOTTINGHAM, NOTTINGHAM NG7 2RD, ENGLAND. UNIV SO CALIF, LOS ANGELES, CA 90089 USA. UNIV UPPSALA, UPPSALA, SWEDEN. UNIV WISCONSIN, CTR COMPREHENS CANC, MADISON, WI 53706 USA. UNDP, UNFPA,WHO,WORLD BANK, SPECIAL PROGRAMME RES DEV & TRAINING HUMAN REPROD, NEW YORK, NY USA. RP Calle, EE (reprint author), RADCLIFFE INFIRM, IMPERIAL CANC RES FUND, CANC EPIDEMIOL UNIT, OXFORD OX2 6HE, ENGLAND. RI Ferraroni, Monica/D-6548-2017; Ranstam, Jonas/A-4386-2009; Beral, Valerie/B-2979-2013; Negri, Eva/B-7244-2013; Boyle, Peter/A-4380-2014; Clavel-Chapelon, Francoise/G-6733-2014; Brinton, Louise/G-7486-2015; Hanson, Robert/O-3238-2015; Richardson, Sylvia/G-4691-2015; Colditz, Graham/A-3963-2009; OI Ferraroni, Monica/0000-0002-4542-4996; La Vecchia, Carlo/0000-0003-1441-897X; Ranstam, Jonas/0000-0002-8287-7273; Negri, Eva/0000-0001-9712-8526; Boyle, Peter/0000-0001-6251-0610; Brinton, Louise/0000-0003-3853-8562; Hanson, Robert/0000-0002-4252-7068; Richardson, Sylvia/0000-0003-1998-492X; Colditz, Graham/0000-0002-7307-0291; Yuan, Jian-Min/0000-0002-4620-3108; Bishop, Tim/0000-0002-8752-8785 NR 71 TC 704 Z9 720 U1 4 U2 39 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 22 PY 1996 VL 347 IS 9017 BP 1713 EP 1727 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA UT396 UT WOS:A1996UT39600008 ER PT J AU Silvente-Poirot, S Wank, SA AF Silvente-Poirot, S Wank, SA TI A segment of five amino acids in the second extracellular loop of the cholecystokinin-B receptor is essential for selectivity of the peptide agonist gastrin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTIONAL EXPRESSION; NEUROKININ-1 RECEPTOR; BINDING; SPECIFICITY; DOMAINS; ASSAY AB The two known receptors mediating the actions of cholecystokinin (CCK) and gastrin, CCK type A (CCKAR) and CCK type B (CCKBR) receptors, are G protein coupled receptors having approximately 50% amino acid homology. Both the CCKAR and CCKBR have high affinity for sulfated CCK peptides, while only the CCKBR has high affinity for gastrin peptides. To determine the structural basis for the selectivity of the CCKBR for gastrin, we first constructed a series of CCKB/AR chimeras in which restriction endonuclease-defined segments of the CCKBR were replaced with the corresponding segments of the CCKAR. Chimeras transiently expressed in COS-1 cells were screened for the selective loss of gastrin affinity according to the displacement of I-125-labeled Bolton-Hunter-CCK-8 binding by gastrin-17-I and CCK-8. The sequence spanning from transmembrane domain III (TM III) to TM. V was the only segment that resulted in the selective loss of gastrin affinity. This segment could account for 100 of the expected 300-fold lower affinity of gastrin-17-I observed for the control CCKAR compared to the control CCKBR. Using site-directed mutagenesis in this segment of the CCKBR, we identified a sequence of 5 amino acids in the second extracellular loop responsible for this 100 fold selective loss in gastrin affinity, I-125-labeled Bolton-Hunter-CCK-8 binding displacement by L365,260 (a CCKBR selective antagonist) was unaffected by the changes in these 5 amino acids. These results present for the first time the identification of the amino acid sequence of the CCKBR conferring the majority of the selectivity for gastrin. C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. RI Poirot, Sandrine/D-5448-2017 NR 34 TC 55 Z9 55 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 21 PY 1996 VL 271 IS 25 BP 14698 EP 14706 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT106 UT WOS:A1996UT10600012 PM 8663021 ER PT J AU Rai, SS Wolff, J AF Rai, SS Wolff, J TI Localization of the vinblastine-binding site on beta-tubulin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VINCA ALKALOIDS; MICROTUBULES INVITRO; TAXOL BINDS; COLCHICINE; PODOPHYLLOTOXIN; POLYMERIZATION; IDENTIFICATION; HYDROLYSIS AB A fluorescent vinblastine derivative, vinblastine-4'-anthranilate, has been shown to inhibit polymerization of rat brain tubulin (IC50 = 4.8 mu M). Binding of the drug to tubulin increases fluorescence intensity, causes a small emission blue shift, and has a quantum yield of 0.037. Fluorescence increases as a function of drug concentration, with a high affinity site and an undetermined number of lower affinity sites. Photolabeling, by exciting the fluorescent drug-tubulin complex at the absorption maximum of anthranilate, yields a covalent adduct confined to beta-tubulin. Its formation is specific in that it is blocked by maytansine or vinblastine, Tryptic hydrolysis identifies a single fluorescent beta-peptide coinciding with residues 175-213. The interactions between various ligands at this central portion of beta-tubulin are discussed. C1 NIDDK,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 42 TC 123 Z9 132 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 21 PY 1996 VL 271 IS 25 BP 14707 EP 14711 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT106 UT WOS:A1996UT10600013 PM 8663038 ER PT J AU Louzao, MC Ribeiro, CMP Bird, GS Putney, JW AF Louzao, MC Ribeiro, CMP Bird, GS Putney, JW TI Cell type-specific modes of feedback regulation of capacitative calcium entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL PHOSPHATE; ACTIVATED CALCIUM; ACINAR-CELLS; MAST-CELLS; THAPSIGARGIN; INHIBITION; PATHWAY; RELEASE; POOL AB The Ca2+ ATPase inhibitor, thapsigargin, activated Ca2+ entry into pancreatic acinar cells, a process known as capacitative calcium entry, In cells loaded with the calcium chelator BAPTA, the transient Ca2+ release was blunted and the rise of [Ca2+](i) on readdition of Ca2+ was slowed, However, the steady-state [Ca2+](i) due to Ca2+ entry was substantially augmented compared with control cells, This indicates that [Ca2+](i) exerts a negative feedback on Ca2+ entry from a compartment buffered by BAPTA and separated from the bulk of cytoplasmic Ca2+. This interaction probably occurs close to the calcium channel where [Ca2+] is higher than in the bulk of the cytoplasm, In support of this interpretation, the slower Ca2+ chelator, EGTA, also blunted the release of Ca2+ and slowed the rise of the sustained [Ca2+](i) phase but failed to augment steady-state [Ca2+](i). In contrast, Ca2+ entry in NIH 3T3 cells was characterized by a transient rise of [Ca2+](i) that decays to near prestimulus levels, This decay in Ca2+ entry also results from negative feedback by Ca2+ because the decrease in Ca2+ entry was reversed by incubation in a Ca2+ deficient medium, However, unlike its effects in acinar cells, BAPTA neither augmented steady-state [Ca2+](i) nor pre vented the inactivation of entry, Rather, in BAPTA-loaded cells, [Ca2+](i) failed to increase substantially suggesting that negative regulation by Ca2+ may occur at a site distinct from the cytoplasmic compartment and inaccessible to cytoplasmic BAPTA, These two distinct types of feedback behavior may indicate subtypes of store-operated calcium channels expressed in different cells or a single type of channel which is differentially regulated in a cell type-specific manner. C1 NIEHS,CALCIUM REGULAT SECT,CELLULAR & MOLEC PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. RI Ribeiro, Carla Maria/A-6955-2009 NR 23 TC 46 Z9 47 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 JUN 21 PY 1996 VL 271 IS 25 BP 14807 EP 14813 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT106 UT WOS:A1996UT10600028 PM 8662975 ER PT J AU Godde, JS Wolffe, AP AF Godde, JS Wolffe, AP TI Nucleosome assembly on CTG triplet repeats SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; MYOTONIC-DYSTROPHY; HISTONE OCTAMER; MESSENGER-RNA; CORE PARTICLE; 5S RNA; DNA; GENE; TRANSCRIPTION; INITIATION AB Expansion of CTG repeat sequences is associated with several human genetic diseases. We have examined the consequences of CTG repeat expansion for nucleosome assembly and positioning. Short CTG repeats are found within the most favored DNA sequences yet defined for nucleosome assembly. We find that as few as six CTG repeats will facilitate nucleosome assembly to a similar extent as the 50 or more repeats found in disease genes. Thus an increase in nucleosome stability on expansion of existing triplet repeats is unlikely to explain the acquisition of the disease phenotype. However, the CTG repeat sequence is efficiently wrapped around the histone octamer, preferring to associate with histones at the nucleosomal dyad. Thus short segments CTG; repeat sequence will facilitate the assembly of a stable positioned nucleosome which might contribute to the expansion phenomenon and the functional organization of chromatin. RP Godde, JS (reprint author), NICHHD,MOLEC EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. NR 62 TC 86 Z9 88 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 21 PY 1996 VL 271 IS 25 BP 15222 EP 15229 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT106 UT WOS:A1996UT10600084 PM 8663027 ER PT J AU Borzi, RM Piacentini, A Monaco, MCG Lisignoli, G Degrassi, A Cattini, L Santi, S Facchini, A AF Borzi, RM Piacentini, A Monaco, MCG Lisignoli, G Degrassi, A Cattini, L Santi, S Facchini, A TI A fluorescent in situ hybridization method in flow cytometry to detect HIV-1 specific RNA SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE fluorescent in situ hybridization; HIV-RNA; flow cytometry ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; INSITU HYBRIDIZATION; GENE-EXPRESSION; RIBOSOMAL-RNA; MESSENGER-RNA; CELLS; INFECTION; TISSUES; RETROVIRUS AB In HIV+ patients, the presence of HIV-RNA in plasma and circulating cells has been reported to be a marker of progression but the percentage of transcriptionally active infected cells remains unclear. We have developed a reliable fluorescent in situ hybridization method for the detection of HIV specific RNA by flow cytometry. The procedure was applied to a panel of chronically infected cell lines and to an acutely infected cell line mimicking normal peripheral blood lymphocytes in susceptibility to HIV-1. The cells were fixed in suspension and hybridized by means of an HIV-1 genomic probe labeled with digoxigenin-11-dUTP. An FTTC-labeled anti-digoxigenin antiserum was then applied and the resulting fluorescence signals were analyzed both by flow cytometry and confocal microscopy. Different procedures for double staining HIV-RNA together with virus induced proteins or surface markers were also developed. Flow cytometric detection of in situ hybridization offers the possibility of analyzing thousands of cells in a few seconds and of collecting multiparametric information at the single cell level, thus providing a potential tool for detecting the rare HIV-RNA expressing cells in peripheral blood samples. C1 IST RIC CODIVILLA PUTTI,IOR,LAB IMMUNOL & GENET,I-40136 BOLOGNA,ITALY. IST RIC CODIVILLA PUTTI,IOR,LAB BIOL CELLULARE & MICROSCOPIA ELETTRON,I-40136 BOLOGNA,ITALY. UNIV BOLOGNA,IST CLIN MED & GASTROENTEROL,I-40126 BOLOGNA,ITALY. UNIV UDINE,DIPARTIMENTO PATOL & MED SPERIMENTALE & CLIN,I-33100 UDINE,ITALY. UNIV UDINE,CONSORZIO RIC BIOMED,I-33100 UDINE,ITALY. NINCDS,LAB MOLEC MED & NEUROSCI,NIH,BETHESDA,MD 20892. RI Santi, Spartaco/Q-7587-2016 OI Santi, Spartaco/0000-0001-9856-7053 NR 36 TC 15 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 21 PY 1996 VL 193 IS 2 BP 167 EP 176 DI 10.1016/0022-1759(96)00070-1 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA UV325 UT WOS:A1996UV32500004 PM 8699030 ER PT J AU Mazumder, A Wang, SM Neamati, N Nicklaus, M Sunder, S Chen, J Milne, GWA Rice, WG Burke, TR Pommier, Y AF Mazumder, A Wang, SM Neamati, N Nicklaus, M Sunder, S Chen, J Milne, GWA Rice, WG Burke, TR Pommier, Y TI Antiretroviral agents as inhibitors of both human immunodeficiency virus type 1 integrase and protease SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA INTEGRATION; INVITRO; RECOMBINATION; MECHANISM AB The human immunodeficiency virus type one integrase (HIV-1 integrase) is required for integration of a double-stranded DNA copy of the viral RNA genome into a host chromosome and for HIV replication. We have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAPE), tyrphostins, and curcumin confer inhibitory activity against HIV-1 integrase. We have investigated the actions of several recently described protease inhibitors, possessing novel. structural features, on HIV-1 integrase. NSC 158393, which contains four 4-hydroxycoumarin residues, was found to exhibit antiviral, antiprotease, and antiintegrase activity. Both the DNA binding and catalytic activities (3'-processing and strand transfer) of integrase were inhibited at micromolar concentrations. Disintegration catalyzed by an integrase mutant containing only the central catalytic domain was also inhibited, indicating that the binding site for these compounds resides in the central 50-212 amino acids of HIV-1 integrase. Binding at or near the integrase catalytic site was also suggested by a global inhibition of the choice of attacking nucleophile in the S'-processing reaction. NSC 158393 inhibited HIV-2, feline, and simian immunodeficiency virus integrases while eukaryotic topoisomerase I was inhibited at higher concentrations, suggesting selective inhibition of retroviral integrases. Molecular modeling studies revealed that the two hydroxyls and two carbonyl moieties in NSC 158393 may represent essential elements of the pharmacophore. Antiviral efficacy was observed with NSC 158393 derivatives that inhibited both HIV protease and integrase, and the most patent integrase inhibitors also-inhibited HIV protease. Hydroxycoumarins may provide lead compounds for development of novel antiviral agents based upon the concurrent inhibition of two viral targets, HIV-1 integrase and protease. C1 NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,MED CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Wang, Shaomeng/E-9686-2010; Burke, Terrence/N-2601-2014 NR 29 TC 133 Z9 138 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 21 PY 1996 VL 39 IS 13 BP 2472 EP 2481 DI 10.1021/jm960074e PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UT694 UT WOS:A1996UT69400007 PM 8691444 ER PT J AU Wang, SM Kazanietz, MG Blumberg, PM Marquez, VE Milne, GWA AF Wang, SM Kazanietz, MG Blumberg, PM Marquez, VE Milne, GWA TI Molecular modeling and site-directed mutagenesis studies of a phorbol ester-binding site in protein kinase C SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR PROMOTERS; 2ND MESSENGERS; ACTIVATION; DIACYLGLYCEROL; PHARMACOPHORE; RECEPTOR; EXPRESSION; MEMORIAL; LECTURE; ANALOGS AB The protein kinase C (PKC) binding site used by PKC activators such as phorbol esters and diacylglycerols (DAGs) has been characterized by means of molecular modeling and site-directed mutagenesis studies. Based upon a NMR-determined solution structure of the second cysteine-rich domain of PKC alpha, molecular modeling was used to study the structures of the complexes formed between the PKC receptor and a number of PKC ligands, phorbol esters, and DAGs. Site-directed mutagenesis studies identified a number of residues important to the binding of phorbol esters to PKC. Analysis of the molecular modeling and mutagenesis results allows the development of a binding model for PKC ligands for which the precise binding nature is defined. The calculated hydrogen bond energies between the protein and various ligands in this binding model are consistent with their measured binding affinities. The binding site for phorbol esters and DAGs is located in a highly conserved, hydrophobic loop region formed by residues 6-12 and 20-27. For the binding elements in phorbol esters, the oxygen at C-20 contributes most to the overall binding energy, and that at C-3 plays a significant role. The oxygen atom at C-12 is not directly involved in the interaction between phorbol esters and PKC. Our results also suggest that the oxygens at C-9 and C-13 are involved in PKC binding, while the oxygen at C-4 is of minimal significance. These results are consistent with known structure-activity relationships in the phorbol ester family of compounds. Comparisons with the X-ray structure showed that although the X-ray data support the results for oxygens at C-3, C-12, and C-20 of phorbol esters, they suggest different roles for oxygens at C-4, C-9, and C-13 Several factors which may contribute to these discrepancies are discussed. C1 NCI,DIV BASIC SCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NCI,DIV BASIC SCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. RI Wang, Shaomeng/E-9686-2010 NR 39 TC 41 Z9 41 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 21 PY 1996 VL 39 IS 13 BP 2541 EP 2553 DI 10.1021/jm950403n PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UT694 UT WOS:A1996UT69400015 PM 8691452 ER PT J AU Draoui, M Hida, T Jakowlew, S Birrer, M Zia, F Moody, TW AF Draoui, M Hida, T Jakowlew, S Birrer, M Zia, F Moody, TW TI PACAP stimulates c-fos mRNAs in small cell lung cancer cells SO LIFE SCIENCES LA English DT Article DE PACAP; PACAP antagonist; c-fos mRNA; nuclear oncogenes; small cell lung cancer ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; HIGH-AFFINITY BINDING; ADENYLATE-CYCLASE; HYPOTHALAMIC POLYPEPTIDE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; SITES; RECEPTOR; VIP AB The effects of PACAP on c-fos mRNA using small cell lung cancer (SCLC) cell was investigated. PACAP-27 (100 nM) increased c-fos mRNA 5-fold using NCI-N417 cells. The increase was concentration dependent with 0.1 nM PACAP-27 half maximally increasing c-fos mRNA. Also the increase in c-fos mRNA caused by PACAP was time dependent; being maximal after 1 hour and returning to basal values after 4 hours. PACAP-38 but not PACAP(28-38) increased c-fos mRNA. One uM PACAP(6-38), a PACAP receptor antagonist, inhibited the increase in c-fos mRNA caused by 1 nM PACAP. These data indicate that PACAP stimulates nuclear oncogene expression in SCLC cells. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. GEORGE WASHINGTON UNIV,MED CTR,DEPT MICROBIOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT MOLEC BIOL,WASHINGTON,DC 20037. NR 31 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 21 PY 1996 VL 59 IS 4 BP 307 EP 313 DI 10.1016/0024-3205(96)00299-8 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UT665 UT WOS:A1996UT66500004 PM 8761002 ER PT J AU Moolten, FL Vonderhaar, BK Mroz, PJ AF Moolten, FL Vonderhaar, BK Mroz, PJ TI Transduction of the herpes thymidine kinase gene into premalignant murine mammary epithelial cells renders subsequent breast cancers responsive to ganciclovir therapy SO HUMAN GENE THERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; NEU ONCOGENE; TUMORS; REGRESSION; CHEMOSENSITIVITY; LYMPHOCYTES; SENSITIVITY; FREQUENT; BEARING; INVIVO AB Drug sensitivity (''suicide'') genes can sensitize cancer cells to chemotherapy, but therapeutic use of these genes is limited by difficulties in delivering them to all areas of established cancers. An alternative strategy entails preemptive introduction of suicide genes into tissues at risk for cancer, thereby imparting drug sensitivity as a clonal property to cancers arising from sensitized cells, To test the preemptive approach, a retroviral vector was used to transduce the herpes thymidine kinase gene into the TM4 line of preneoplastic murine mammary epithelial cells to yield a clonal subline sensitized to the guanosine analog ganciclovir, Ganciclovir therapy of tumors that arose from the transduced cells retarded tumor growth and induced durable regressions in 7/20 mice; ganciclovir was ineffective against control tumors, The results imply the possibility of reducing cancer lethality by actions taken before cancers arise. C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP Moolten, FL (reprint author), EDITH NOURSE ROGERS MEM VET ADM HOSP,200 SPRINGS RD,BEDFORD,MA 01730, USA. NR 31 TC 14 Z9 14 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 JUN 20 PY 1996 VL 7 IS 10 BP 1197 EP 1204 DI 10.1089/hum.1996.7.10-1197 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD318 UT WOS:A1996WD31800002 PM 8793544 ER PT J AU Leimig, T Brenner, M Ramsey, J Vanin, E Blaese, M Dilloo, D AF Leimig, T Brenner, M Ramsey, J Vanin, E Blaese, M Dilloo, D TI High-efficiency transduction of freshly isolated human tumor cells using adenoviral interleukin-2 vectors SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; HUMAN NEUROBLASTOMA-CELLS; ABROGATES TUMORIGENICITY; CYSTIC-FIBROSIS; EXPRESSION; RETROVIRUS; IMMUNITY; MELANOMA; TOXICITY; THERAPY AB Tumor cells genetically modified to express immunostimulatory molecules can produce high levels of antitumor immunity in rodent models, Although a number of clinical trials are currently in progress to assess the value of the approach in human disease, almost all require ex vivo transduction of cultured tumor cells with retroviral vectors, This process is not feasible for many human malignancies, hampering clinical evaluation of the approach, We have used an E1a,1b/E3 deletion mutant of adenovirus containing either the lacZ or the human interleukin-2 (IL-2) gene to transduce human neuroblastoma cells, This vector transduces fresh neuroblastoma cells and neuroblastoma cell lines with an efficiency of 80-90%, compared to an efficiency of 0-14% obtained with retroviral vectors, Cells transduced with the IL-2 adenovector produce up to 12,000 pg of IL-2/10(6) cells/24 hr. IL-2 adenovector-transduced neuroblasts are immunostimulatory; when they are cultured with patient lymphocytes, they increase the proportion of DR(+) T cells and generate major histocompatibility complex (MHC) unrestricted cytotoxic effector cells active against parental (nontransduced) tumor cells, We conclude that Il-2 adenovector can be used to transduce freshly isolated human tumor cells efficiently, which will then produce immunomodulatory quantities of the cytokine, The use of adenoviral rather than retroviral vectors facilitates preparation of human tumor ''vaccines'' and these vectors are now being used in our clinical study of neuroblastoma patients. C1 ST JUDE CHILDRENS RES HOSP, DIV BONE MARROW TRANSPLANTAT, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPT HEMATOL, MEMPHIS, TN 38105 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20862 USA. GENET THERAPY INC, GAITHERSBURG, MD 20878 USA. NR 26 TC 28 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN 20 PY 1996 VL 7 IS 10 BP 1233 EP 1239 DI 10.1089/hum.1996.7.10-1233 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD318 UT WOS:A1996WD31800005 PM 8793547 ER PT J AU Figurov, A PozzoMiller, LD Olafsson, P Wang, T Lu, B AF Figurov, A PozzoMiller, LD Olafsson, P Wang, T Lu, B TI Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus SO NATURE LA English DT Article ID LONG-TERM POTENTIATION; POSTNATAL RAT-BRAIN; MESSENGER-RNA; AREA CA1; BDNF; NT-3; ENHANCEMENT; EXPRESSION; PLASTICITY; INDUCTION AB NEUROTROPHINS promote neuronal survival and differentiation, but the fact that their expression is modified by neuronal activity, suggests a role in regulating synapse development and plasticity(1-3). In developing hippocampus, the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB(4-7) increases in parallel with the ability to undergo long-term potentiation (LTP)(8-10). Here me report a mechanism by which BDNF modulates hippocampal LTP. Exogenous BDNF promoted the induction of LTP by tetanic stimulation in young (postnatal day 12-13) hippocampal slices, which in the absence of BDNF show only short-term potentiation (STP), This effect was due to an enhanced ability of hippocampal synapses to respond to tetanic stimulation, rather than to a direct modulation of the LTP-triggering mechanism. A TrkB-IgG fusion protein, which scavenges endogenous BDNF11, reduced the synaptic responses to tetanus as well as the magnitude of LTP in adult hippocampus. C1 NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110. RI Lu, Bai/A-4018-2012; yu, yan/C-2322-2012 NR 30 TC 740 Z9 754 U1 0 U2 15 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 20 PY 1996 VL 381 IS 6584 BP 706 EP 709 DI 10.1038/381706a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UR979 UT WOS:A1996UR97900055 PM 8649517 ER PT J AU Landesman, SH Kalish, LA Burns, DN Minkoff, H Fox, HE Zorrilla, C Garcia, P Fowler, MG Mofenson, L Tuomala, R AF Landesman, SH Kalish, LA Burns, DN Minkoff, H Fox, HE Zorrilla, C Garcia, P Fowler, MG Mofenson, L Tuomala, R TI Obstetrical factors and the transmission of human immunodeficiency virus type I from mother to child SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TO-INFANT TRANSMISSION; MONONUCLEAR CELL COCULTURES; HIV-INFECTION; VERTICAL TRANSMISSION; SEROPOSITIVE WOMEN; CD4 PERCENTAGE; REPLICATION; RISK; SECRETIONS; COCAINE AB Background, A substantial proportion of perinatally acquired infections with the human immunodeficiency virus type 1 (HIV-1) occur at or near delivery, which suggests that obstetrical factors may have an important influence on transmission, We evaluated the relation of such factors and other variables to the perinatal transmission of HIV-1. Methods. The Women and Infants Transmission Study is a prospective, observational study of HIV-1-infected women who were enrolled during pregnancy and followed with their infants for three years after delivery, We studied obstetrical, clinical, immunologic, and virologic data on 525 women who delivered live singleton infants whose HIV-1-infection status was known as of August 31, 1994. Results. Among mothers with membranes that ruptured more than four hours before delivery, the rate of transmission of HIV-1 to the infants was 25 percent, as compared with 14 percent among mothers with membranes that ruptured four hours or less before delivery, In a multivariate analysis, the presence of ruptured membranes for more than four hours nearly doubled the risk of transmission (odds ratio, 1.82; 95 percent confidence interval, 1.10 to 3.00; P = 0.02), regardless of the mode of delivery, The other maternal factors independently associated with transmission were illicit-drug use during pregnancy (odds ratio, 1.90; 95 percent confidence interval, 1.14 to 3.16; P = 0.01), low antenatal CD4+ lymphocyte count (<29 percent of total lymphocytes) (odds ratio, 2.82; 1.67 to 4.76; P<0.001), and birth weight <2500 g (odds ratio, 1.86; 1.03 to 3.34; P = 0.04), Conclusions. The risk of transmission of HIV-1 from mother to infant increases when the fetal membranes rupture more than four hours before delivery. C1 SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,BROOKLYN,NY 11203. NEW ENGLAND RES INST,WATERTOWN,MA 02172. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,DEPT OBSTET & GYNECOL,WASHINGTON,DC. UNIV PUERTO RICO,DEPT OBSTET & GYNECOL,SAN JUAN,PR 00936. NORTHWESTERN UNIV,SCH MED,DEPT OBSTET & GYNECOL,CHICAGO,IL 60611. NIAID,VACCINE TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. RP Landesman, SH (reprint author), SUNY HLTH SCI CTR,DEPT MED,DIV INFECT DIS,450 CLARKSON AVE,BOX 122,BROOKLYN,NY 11203, USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-82505, AI-82506, AI-82507] NR 59 TC 279 Z9 298 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 1996 VL 334 IS 25 BP 1617 EP 1623 DI 10.1056/NEJM199606203342501 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UQ706 UT WOS:A1996UQ70600001 PM 8628356 ER PT J AU Waytes, AT Rosen, FS Frank, MM AF Waytes, AT Rosen, FS Frank, MM TI Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANGIONEUROTIC-EDEMA; ESTERASE INHIBITOR; ACID THERAPY; C1-INHIBITOR; MANAGEMENT AB Background. Hereditary angioedema results from a congenital deficiency of functional C1 inhibitor and is characterized by episodic bouts of edema, which may be life-threatening when they involve the larynx. We evaluated the effectiveness of a C1 inhibitor concentrate in the prevention and treatment of attacks of hereditary angioedema. The concentrate was vapor-heated to inactivate hepatitis and hunan immunodeficiency viruses. Methods. We conducted two double-blind, placebo-controlled studies. The first was a crossover study consisting of two 17-day trials in which prophylactic infusions of either C1 inhibitor (25 plasma units per kilogram of body weight) or placebo were given intravenously every third day to six patients with hereditary angioedema. The second study was conducted in patients with acute attacks of hereditary angioedema and assessed the length of time to a clinical response after infusions of either 25 plasma units of C1 inhibitor per kilogram (55 infusions in 11 patients). Results. The infusions of C1 inhibitor concentrate resulted in close to normal functional levels of C1 inhibitor and C4. As compared with placebo, prophylactic infusions of C1 inhibitor resulted in significantly lower daily symptom scores for the severity of edema of the extremities (P < 0.01), larynx (P < 0.05), abdomen (P < 0.05), and genitourinary tract (P < 0.05). Likewise, during the treatment study the time from the start of an infusion to the beginning of improvement in symptoms was shorter for the C1 inhibitor infusions than the placebo infusions (55 vs. 563 minutes, P < 0.001). There was no evidence of toxicity. Conclusions. Infusions of a vapor-heated C1 inhibitor concentrate are safe and effective means of both preventing attacks of hereditary angioedema and treating acute attacks. (C) 1996, Massachusetts Medical Society. C1 CHILDRENS HOSP,CTR BLOOD RES,DIV IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. FU NCRR NIH HHS [GCRC RR-02172] NR 27 TC 222 Z9 224 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 1996 VL 334 IS 25 BP 1630 EP 1634 DI 10.1056/NEJM199606203342503 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UQ706 UT WOS:A1996UQ70600003 PM 8628358 ER PT J AU Goodfriend, TL Elliott, ME Catt, KJ AF Goodfriend, TL Elliott, ME Catt, KJ TI Drug therapy - Angiotensin receptors and their antagonists SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SMOOTH-MUSCLE CELLS; II RECEPTOR; GLOMERULOSA CELLS; NORMAL VOLUNTEERS; HEALTHY-SUBJECTS; CALCIUM SIGNAL; HYPERTROPHY; INHIBITION; RESPONSES; HYPERPLASIA C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP Goodfriend, TL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 82 TC 418 Z9 448 U1 0 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 1996 VL 334 IS 25 BP 1649 EP 1654 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UQ706 UT WOS:A1996UQ70600007 PM 8628362 ER PT J AU Ray, ME Su, YA Meltzer, PS Trent, JM AF Ray, ME Su, YA Meltzer, PS Trent, JM TI Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma SO ONCOGENE LA English DT Article DE malignant melanoma; chromosome 6; tumor suppression ID LONG ARM; EXPRESSION; IDENTIFICATION; SEARCH AB Melanocytic transformation is thought to occur by the sequential accumulation of genetic alterations, Evidence implicating human chromosome-6 as a site for a gene(s) involved in melanoma suppression comes from studies of LOH [loss of heterozygosity], cytogenetics and biologic reversion of tumorigenicity following the introduction of a normal chromosome 6 by microcell-mediated chromosome transfer (Trent et al., 1990), Using a tumorigenic melanoma cell line (UACC 903) and a chromosome-6 suppressed melanoma subline [UACC 903 (+6)], we have isolated a series of genes uniquely expressed in the suppressed subline, A modified PCR-based cDNA subtraction technique was used to generate subtracted cDNA sublibraries for both the parental and (+6) suppressed cells, A total of 32 randomly selected clones from the suppressed sublibrary were isolated and examined, with 24 detecting a transcript by Northern analysis, Of these 24 clones, 21 (88%) demonstrated elevated expressed by Northern analysis in the suppressed subline relative to the tumorigenic parental cell line, In 6/21 differentially expressed clones (29%), expression was exclusive to the suppressed subline, Partial sequence analysis and database searching of these clones indicated that 5/6 were novel with one representing a previously characterized gene, Chromosomal localization of the five novel clones was performed following PCR amplification of a human/rodent somatic cell hybrid mapping panel or fluorescent in situ hybridization, One cDNA (termed AIM1) was localized to a band-region of chromosome 6 frequently deleted in melanomas (6q21), This novel approach should facilitate the identification of genes whose expression is causally related to the suppressed phenotype. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NR 21 TC 45 Z9 47 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 20 PY 1996 VL 12 IS 12 BP 2527 EP 2533 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UW487 UT WOS:A1996UW48700006 PM 8700511 ER PT J AU Matoskova, B Wong, WT Seki, N Nagase, T Nomura, N Robbins, KC DiFiore, PP AF Matoskova, B Wong, WT Seki, N Nagase, T Nomura, N Robbins, KC DiFiore, PP TI RN-tre identifies a family of tre-related proteins displaying a novel potential protein binding domain SO ONCOGENE LA English DT Article DE eps8; SH3; tre; signal transduction ID INSITU HYBRIDIZATION; CYTOGENETIC FINDINGS; GENE; ONCOGENE; CLONING; KINASE; GTPASE AB Eps8 is a recently identified SH3-containing substrate for tyrosine kinase receptors, To understand the role of eps8 in receptor-mediated signaling, we cloned cDNAs encoding proteins that bind to its SH3 domain. One of these cDNAs predicts the synthesis of an 828 amino acid protein with homology to the N-terminal region of the tre oncogene. We designated this protein RN-tre for Related to the N-terminus of tre. RN-tre is ubiquitously expressed and maps to 10p13, a region known to be involved in translocations in various leukemias. Tn addition, a 10p13 monosomy syndrome, characterized by developmental alterations, has been reported, The regional homology between RN-tre and tre, which is limited to their N-terminal portion, prompted us to investigate the origin of the tre oncogene transcriptional unit. We were able to show that tre is the fusion product of a 5' genetic element, homologous to RN-tre and a 3' element, encoding a de-ubiquinating enzyme. Moreover, we identified, within the N-terminus of RN-tre and tre, a domain (named TrH, for Tre Homology), which is conserved within several proteins from yeast to mammals and has protein-binding properties in vitro. C1 EUROPEAN INST ONCOL, DEPT EXPTL ONCOL, IEO, I-20141 MILAN, ITALY. NIDR, NIH, CELLULAR DEV & ONCOL LAB, BETHESDA, MD 20892 USA. NCI, NIH, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. KAZASA DNA RES INST, CHIBA 292, JAPAN. IST MICROBIOL, FAC MED & CHIRURG, BARI, ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 40 TC 22 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUN 20 PY 1996 VL 12 IS 12 BP 2563 EP 2571 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UW487 UT WOS:A1996UW48700010 PM 8700515 ER PT J AU Vairapandi, M Balliet, AG Fornace, AJ Hoffman, B Liebermann, DA AF Vairapandi, M Balliet, AG Fornace, AJ Hoffman, B Liebermann, DA TI The differentiation primary response gene MyD118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21(WAF1/CIP1) SO ONCOGENE LA English DT Article DE MyD118; p21(WAF1); PCNA; Gadd45; myeloid differentiation; apoptosis ID LEUKEMIA INHIBITORY FACTOR; IMMEDIATE EARLY RESPONSE; CYCLIN-DEPENDENT KINASES; TERMINAL DIFFERENTIATION; GROWTH-ARREST; CELL-DEATH; C-MYC; DNA-REPLICATION; APOPTOSIS; P53 AB Towards dissecting the regulation of terminal differentiation, including growth arrest and apoptosis, myeloid differentiation primary response (MyD) genes, induced in the absence of de novo protein synthesis following induction of M1 myeloblastic leukemia cells for terminal differentiation have been isolated. MyD118 was one of the novel MyD genes cloned, subsequently observed also to be a primary response gene to TGF-beta, which induces M1 cells for growth arrest and apoptosis uncoupled from differentiation. The MyD118 encoded protein was observed to be remarkably similar to the protein encoded by Gadd45, a growth arrest and DNA damage induced gene, regulated in part by the tumor suppressor p53, Though evidence has accumulated that MyD118 functions as an important modulator of negative growth control both in hematopoietic and non-hematopoietic cells, its mechanism of action is unknown, To better understand the role(s) of MyD118 in negative growth control, we have analysed the expression and biological characteristics of the MyD118 protein, compared to the Gadd45 protein, in distinct pathways of growth arrest and apoptosis, including p53 dependent and independent pathways either coupled or uncoupled from differentiation. It is shown that MyD118 and Gadd45 differentially accumulated upon induction of distinct pathways of growth arrest and apoptosis; notably, MyD118, but not Gadd45, was induced by TGF-beta, whereas Gadd45, but not MyD118, was induced by activating wild type (wt) p53 function, It is also shown that MyD118 is a nuclear protein, which regardless of the pathway induced, predominantly localized within the cell nucleus, and interacted with the DNA replication and repair protein PCNA and the cyclin dependent kinase inhibitor P21(WAF1/CIP1). MyD118 also modestly stimulated DNA repair in vitro. All of these characteristics were shared with Gadd45, Finally, it is demonstrated that MyD118, Gadd45 and p21 synergized in the suppression of colony formation by NIH3T3 cells, Taken together, these findings demonstrate that MyD118 and Gadd45 are representative of a new protein family that share remarkable functional similarities in the control of distinct pathways of negative growth, including the suppression of cellular growth and programmed cell death. C1 TEMPLE UNIV,SCH MED,FELS INST CANC & MOLEC BIOL,PHILADELPHIA,PA 19140. TEMPLE UNIV,SCH MED,DEPT BIOCHEM,PHILADELPHIA,PA 19140. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,NIH,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [1R01CA43618, 5P30 CA12227] NR 78 TC 147 Z9 147 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 20 PY 1996 VL 12 IS 12 BP 2579 EP 2594 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UW487 UT WOS:A1996UW48700012 PM 8700517 ER PT J AU Petropoulos, CJ Givol, I Hughes, SH AF Petropoulos, CJ Givol, I Hughes, SH TI Comparative analysis of the structure and function of the chicken c-myc and v-myc genes: v-myc is a more potent inducer of cell proliferation and apoptosis than c-myc SO ONCOGENE LA English DT Article DE c-myc; cell cycle; apoptosis; chicken; transcription initiation; translation initiation ID WEIGHT NONMUSCLE TROPOMYOSIN; AVIAN MYELOCYTOMATOSIS VIRUS; NUCLEOTIDE-SEQUENCE; RETROVIRUS VECTORS; TRANSFORMING GENE; INDUCED LYMPHOMAS; BURKITT-LYMPHOMA; BURSAL LYMPHOMAS; GROWTH-FACTOR; 1ST EXON AB To gain a more complete understanding of c-myc regulation in chickens, we have completed the structural characterization of the chicken c-myc gene and have begun to investigate c-myc transcription and protein expression. A comparison of c-myc Structure and expression between mammals and birds presents an enigma: there are striking similarities in the pattern of gene expression in the absence of obvious sequence similarities in the controlling elements, We have begun to investigate c-myc and v-myc function using retroviral vectors that differ solely in the Myc proteins that they express. We show that while the overexpression of the smaller c-Myc protein is sufficient to induce morphological transformation in chicken embryo fibroblasts, overexpression of v-Myc provides a stronger signal for cells to enter the cell cycle and is a more potent inducer of apoptosis than c-Myc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 59 TC 20 Z9 20 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 20 PY 1996 VL 12 IS 12 BP 2611 EP 2621 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UW487 UT WOS:A1996UW48700015 PM 8700520 ER PT J AU Matoskova, B Wong, WT Nomura, N Robbins, KC DiFiore, PP AF Matoskova, B Wong, WT Nomura, N Robbins, KC DiFiore, PP TI RN-tre specifically binds to the SH3 domain of eps8 with high affinity and confers growth advantage to NIH3T3 upon carboxy-terminal truncation SO ONCOGENE LA English DT Article DE eps8; SH3; tre; signal transduction ID GUANINE-NUCLEOTIDE EXCHANGE; ADAPTER PROTEIN; TYROSINE KINASE; EGF RECEPTOR; GRB2; RAS; ONCOGENE; CELLS; SOS; ACTIVATOR AB We isolated a cDNA encoding a protein, RN-tre, which shows homology to the N-terminus of the tre oncogene product and has SH3-binding ability as well as an evolutionarily conserved domain, termed TrH, with protein-binding ability in vitro. In the present study, we identify the product of the RN-tre gene as a 97 - 100 kDa protein. We demonstrate stable association in vivo and in vitro between RN-tre and eps8, mediated by the SH3 domain of the latter. In vitro, RN-tre displayed remarkable preference for binding to the eps8-SH3, as compared to eight other SH3s. The Kd for the in vitro interaction between RN-tre and eps8-SH3 was between 10(-8) and 10(-7) M. A role for RN-tre in cell proliferation was suggested by the finding that a C-terminal truncated mutant was able to confer proliferative advantage and reduced serum-requirement to NIH3T3 fibroblasts. Finally, comparison of the structure and biological activities of RN-tre and of the tre oncogene product, provided insight into the mechanism of oncogenic activation of tre. C1 IST EUROPEO ONCOL, DEPT EXPTL ONCOL, I-20141 MILAN, ITALY. NIDR, CELLULAR DEV & ONCOL LAB, NIH, BETHESDA, MD 20892 USA. NCI, LAB CELLULAR & MOL BIOL, NIH, BETHESDA, MD 20892 USA. KAZASA DNA RES INST, CHIBA 292, JAPAN. FAC MED & CHIRURG, IST MICROBIOL, BARI, ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 31 TC 34 Z9 35 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 20 PY 1996 VL 12 IS 12 BP 2679 EP 2688 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UW487 UT WOS:A1996UW48700022 PM 8700527 ER PT J AU Velasco, JA Zimonjic, DB Popescu, NC Cansado, J DiPaolo, JA Albor, A Notario, V AF Velasco, JA Zimonjic, DB Popescu, NC Cansado, J DiPaolo, JA Albor, A Notario, V TI Tissue-specific expression, evolutionary conservation and localization of the cph proto-oncogene on Syrian hamster chromosome X SO ONCOGENE LA English DT Article DE cph oncogene; evolution; FISH; gene expression; gene mapping; Syrian hamster ID BANDING PATTERNS; GENES; SEQUENCES; CELLS AB Treatment of Syrian hamster embryo fibroblasts with a single dose of 3-methylcholanthrene caused the activation of the transforming potential of cellular sequences (Notario et al,, Oncogene 5: 1425-1430, 1990), which were subsequently isolated by cosmid rescue techniques, and further identified as a novel oncogene, termed cph because of its involvement in the carcinogenic progression of hamster embryo cells (Velasco ed al., Oncogene 9: 2065-2069, 1994), We have analysed the expression of the cph proto-oncogene in adult Syrian hamster tissues by northern hybridization using cph-specific genomic probes, The three cph transcripts expressed in normal and neoplastic Syrian hamster embryo cells in culture (5.0, 3.5 and 2.0 kb) were also present in most adult tissues, although different mRNA species, most likely resulting from alternative splicing events, were expressed in testes, The highest steady-state level of cph mRNA was found in kidney, whereas cph expression was nearly undetectable in skin and skeletal muscle, Southern blot analyses of DNAs from other eucaryotic organisms were performed under moderate stringency conditions with a Syrian hamster-specific cph probe, Discrete cpk-hybridizing sequences were present in genomes from yeast to mammalian species, including humans, thus demonstrating that cph is a highly conserved gene in eucaryotic evolution, Using fluorescence in situ hybridization (FISH), we have determined also the chromosomal Idealization of the cph proto-oncogene in the hamster genome, FISH experiments demonstrated that cph is a single copy gene, localized on the euchromatic short arm of the X chromosome, at region Xpa7, Because chromosome X is frequently involved in structural alterations in neoplastic Syrian hamster cells transformed by chemical carcinogens and oncogenic viruses, the localization of the cph locus on this chromosome supports the notion that the cph oncogene plays a role in the malignant conversion of chemically transformed hamster fibroblasts, The wide range of tissue-specific expression and species-specific distribution of cph strongly suggest that the normal function of the cph protein product(s) may be essential for metabolic processes involved in the regulation of cell proliferation and survival. C1 GEORGETOWN UNIV,MED CTR,DEPT RADIAT MED,WASHINGTON,DC 20007. NCI,BIOL LAB,NIH,BETHESDA,MD. RI Cansado, Jose/K-5212-2014 FU NCI NIH HHS [CA64472] NR 31 TC 17 Z9 17 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 20 PY 1996 VL 12 IS 12 BP 2713 EP 2717 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UW487 UT WOS:A1996UW48700026 PM 8700531 ER PT J AU Lindberg, DAB Humphreys, BL AF Lindberg, DAB Humphreys, BL TI Medical informatics SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article RP Lindberg, DAB (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 19 PY 1996 VL 275 IS 23 BP 1821 EP 1822 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UQ152 UT WOS:A1996UQ15200028 PM 8642729 ER PT J AU Tejeda, HA Green, SB Trimble, EL Ford, L High, JL Ungerleider, RS Friedman, MA Brawley, OW AF Tejeda, HA Green, SB Trimble, EL Ford, L High, JL Ungerleider, RS Friedman, MA Brawley, OW TI Representation of African-Americans, Hispanics, and whites in National Cancer Institute cancer treatment trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CLINICAL-TRIALS; PATIENT AB Background: The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. Purpose: Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. Methods: During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups: birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. Results: Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. Conclusions: Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. Implications: This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials. C1 US FDA,ROCKVILLE,MD 20857. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT DIAG & CTR,CANC TREATMENT EVALUAT PROGRAM,BETHESDA,MD 20892. NR 18 TC 147 Z9 147 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 19 PY 1996 VL 88 IS 12 BP 812 EP 816 DI 10.1093/jnci/88.12.812 PG 5 WC Oncology SC Oncology GA UR094 UT WOS:A1996UR09400011 PM 8637047 ER PT J AU Curtis, RE Boice, JD Shriner, DA Hankey, BF Fraumeni, JF AF Curtis, RE Boice, JD Shriner, DA Hankey, BF Fraumeni, JF TI Second cancers after adjuvant tamoxifen therapy for breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article C1 NCI,CANC STAT BRANCH,BETHESDA,MD 20892. RP Curtis, RE (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 12 TC 136 Z9 136 U1 1 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 19 PY 1996 VL 88 IS 12 BP 832 EP 834 DI 10.1093/jnci/88.12.832 PG 3 WC Oncology SC Oncology GA UR094 UT WOS:A1996UR09400014 PM 8637050 ER PT J AU Zamudio, F Wolf, KM Martin, BM Possani, LD Chiappinelli, VA AF Zamudio, F Wolf, KM Martin, BM Possani, LD Chiappinelli, VA TI Two novel alpha-neurotoxins isolated from the Taipan snake, Oxyuranus scutellatus, exhibit reduced affinity for nicotinic acetylcholine receptors in brain and skeletal muscle SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; RAT HIPPOCAMPAL-NEURONS; PHARMACOLOGICAL PROPERTIES; KAPPA-BUNGAROTOXIN; OPTIC LOBE; FUNCTIONAL-PROPERTIES; S-SCUTELLATUS; BINDING; VENOM; CHICK AB Three novel toxic peptides were purified to homogeneity from the venom of the Australian taipan snake, Oxyuranus scutellatus scutellatus. On the basis of complete amino acid sequence analyses, two of these toxins belong to the family of short-chain alpha-neurotoxins found in elapid and hydrophid snake venoms and are the first postsynaptic neurotoxins identified in taipan venom. Radioligand binding studies confirm that taipan toxins 1 and 2 inhibit the binding of [I-125]-alpha-bungarotoxin to nicotinic acetylcholine receptors in skeletal muscle with IC50 values of 2.4-2.5 nM but are 5-fold less potent in this assay than alpha-bungarotoxin or the two short-chain alpha-neurotoxins erabutoxin a and erabutoxin b. Taipan toxins 1 and 2 do not antagonize [I-125]-alpha-bungarotoxin binding to central neuronal nicotinic receptors at concentrations up to 3 mu M. We find that erabutoxin a and erabutoxin b do inhibit the binding of [I-125]-alpha-bungarotoxin to central neuronal nicotinic receptors but are over 350-fold less potent than long-chain alpha-neurotoxins at these receptors. The novel alpha-neurotoxins from taipan venom do not inhibit the binding of [H-3]nicotine to high-affinity nicotine receptors in brain, a property they share with alpha-bungarotoxin and the erabutoxins. The results demonstrate that at least two neuromuscular junction-blocking peptides are present in taipan venom. Nonconservative substitutions at position 32 in both taipan toxin 1 and 2 may be responsible for the observed decreases in affinities of the toxins of 5-fold for muscle receptors (compared to alpha-bungarotoxin) and over 10-fold for alpha-bungarotoxin-sensitive nicotinic receptors in brain (compared to the structurally similar short-chain alpha-neurotoxins erabutoxin a and erabutoxin b). C1 ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. UNIV NACL AUTONOMA MEXICO,INST BIOTECNOL,DEPT MOLEC RECOGNIT & STRUCT BIOL,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. RI Possani, Lourival/J-2397-2013 FU NINDS NIH HHS [NS17574] NR 36 TC 25 Z9 27 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 18 PY 1996 VL 35 IS 24 BP 7910 EP 7916 DI 10.1021/bi9600761 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UR904 UT WOS:A1996UR90400033 PM 8672493 ER PT J AU Pettit, GR Orr, B Herald, DL Doubek, DL Tackett, L Schmidt, JM Boyd, MR Pettit, RK Hooper, JNA AF Pettit, GR Orr, B Herald, DL Doubek, DL Tackett, L Schmidt, JM Boyd, MR Pettit, RK Hooper, JNA TI Isolation and X-ray crystal structure of racemic xestospongin D from the Singapore marine sponge Niphates sp SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ALKALOIDS AB (+/-)-Xestospongin D (2) has been isolated from the Singapore marine sponge Niphates sp. The natural product was found to be racemic in contrast to earlier isolations of (+)-xestospongin D from Xestospongia and Haliclona species. The (+/-)-xestospongin D was found to inhibit growth of certain human cancer cell lines comprising the NCI panel (e.g., leukemia subpanel, mean GI(50) 3.62 +/- 2.02 x 10(-6)M; breast subpanel, mean GIS, 4.53 +/- 1.98 x 10(-6)M) as well as the murine P388 lymphocytic leukemia (ED(50) 1.7 mu g/mL) and the bacterium Micrococcus luteus. Copyright (C) 1996 Elsevier Science Ltd C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DTP,DGT,FREDERICK,MD 21702. WESTERN OREGON STATE COLL,DEPT BIOL,MONMOUTH,OR 97361. QUEENSLAND MUSEUM,SESSILE MARINE INVERTEBRATES,BRISBANE,QLD 4101,AUSTRALIA. RP Pettit, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 24 TC 17 Z9 17 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 18 PY 1996 VL 6 IS 12 BP 1313 EP 1318 DI 10.1016/0960-894X(96)00225-9 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA UU381 UT WOS:A1996UU38100005 ER PT J AU Dubois, EP Robbins, JB Pozsgay, V AF Dubois, EP Robbins, JB Pozsgay, V TI Chemical approaches to bacterial vaccines. Synthesis of mycobacterial oligosaccharide-protein conjugates for use as serodiagnostics and immunogens SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ANTIGENS AB Di- to penta-saccharide fragments (2-5) of Polysaccharide II (PS-II) of Mycobacterium tuberculosis were synthesized in spacer-linked form in a stepwise fashion using a new glycosyl donor featuring a trans-fused isopropylidene diol-protecting group. Covalent attachment of the oligosaccharides to proteins provides semi-synthetic antigens and immunogens which are being used to probe the role of PS-II as a possible mycobacterial antigen. C1 NICHHD,NIH,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NR 23 TC 3 Z9 3 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 18 PY 1996 VL 6 IS 12 BP 1387 EP 1392 DI 10.1016/0960-894X(96)00235-1 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA UU381 UT WOS:A1996UU38100020 ER PT J AU Forrest, D Hanebuth, E Smeyne, RJ Everds, N Stewart, CL Wehner, JM Curran, T AF Forrest, D Hanebuth, E Smeyne, RJ Everds, N Stewart, CL Wehner, JM Curran, T TI Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: Evidence for tissue-specific modulation of receptor function SO EMBO JOURNAL LA English DT Article DE c-erbA; genetic disease; thyroid hormone receptor; transcription ID GENERALIZED RESISTANCE; MOUSE THYROTROPIN; DIFFERENTIAL EXPRESSION; MESSENGER-RNAS; RAT-BRAIN; ALPHA; GENE; DOMINANT; HYPOTHYROIDISM; INHIBITION AB The diverse functions of thyroid hormone (T3) are presumed to be mediated by two genes encoding the related receptors, TR alpha and TR beta, However, the in vivo functions of TR alpha and TR beta are undefined, Here, we report that targeted inactivation of the mouse TR beta gene results in goitre and elevated levels of thyroid hormone, Also, thyroid-stimulating hormone (TSH), which is released by pituitary thyrotropes and which is normally suppressed by increased levels of thyroid hormone, was present at elevated levels in homozygous mutant (Thrb(-/-)) mice, These findings suggest a unique role for TR beta that cannot be substituted by TR alpha in the T3-dependent feedback regulation of TSH transcription. Thrb(-/-) mice provide a recessive model for the human syndrome of resistance to thyroid hormone (RTH) that exhibits a similar endocrine disorder but which is typically caused by dominant TR beta mutants that are transcriptional inhibitors, It is unknown whether TR alpha, TR beta or other receptors are targets for inhibition in dominant RTH; however, the analysis of Thrb(-/-) mice suggests that antagonism of TR beta-mediated pathways underlies the disorder of the pituitary-thyroid axis. Interestingly, in the brain, the absence of TR beta may not mimic the defects often associated with dominant RTH, since no overt behavioural or neuroanatomical abnormalities were detected in Thrb(-/-) mice, These data define in vivo functions for TR beta and indicate that specificity in T3 signalling is conferred by distinct receptor genes. C1 UNIV COLORADO, INST BEHAV GENET, BOULDER, CO 80309 USA. HOFFMANN LA ROCHE INC, DEPT NEUROGENET, NUTLEY, NJ 07110 USA. HOFFMANN LA ROCHE INC, DEPT PATHOL & TOXICOL, NUTLEY, NJ 07110 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, LAB CANC & DEV BIOL, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, DEPT DEV NEUROBIOL, MEMPHIS, TN 38105 USA. RP Forrest, D (reprint author), MT SINAI MED CTR, DEPT HUMAN GENET, 1 GUSTAVE L LEVY PL, NEW YORK, NY 10029 USA. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011 OI Curran, Tom/0000-0003-1444-7551; FU NCI NIH HHS [P30 CA21765]; NIAAA NIH HHS [AA-00141]; NIMH NIH HHS [MH-48663] NR 57 TC 277 Z9 285 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 17 PY 1996 VL 15 IS 12 BP 3006 EP 3015 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV920 UT WOS:A1996UV92000012 PM 8670802 ER PT J AU Ramsden, DA McBlane, JF vanGent, DC Gellert, M AF Ramsden, DA McBlane, JF vanGent, DC Gellert, M TI Distinct DNA sequence and structure requirements for the two steps of V(D)J recombination signal cleavage SO EMBO JOURNAL LA English DT Article DE DNA double strand breaks; DNA hairpins; DNA unpairing; RAG1; RAG2 ID MOUSE THYMOCYTES; TRANSPOSOSOME; MUTATIONS; MOLECULES; PROTEIN AB Cleavage of V(D)J recombination signals by purified RAG1 and RAG2 proteins permits the dissection of DNA structure and sequence requirements, The two recognition elements of a signal (nonamer and heptamer) are used differently, and their cooperation depends on correct helical phasing. The nonamer is most important for initial binding, while efficient nicking and hairpin formation require the heptamer sequence, Both nicking and hairpin formation are remarkably tolerant of variations in DNA structure, Certain flanking sequences inhibit hairpin formation, but this can be bypassed by base unpairing, and even a completely single-stranded signal sequence is well utilized, We suggest that DNA unpairing around the signal-coding border is essential for the initiation of V(D)J recombination. C1 NIDDKD,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA084442] NR 32 TC 135 Z9 135 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 17 PY 1996 VL 15 IS 12 BP 3197 EP 3206 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV920 UT WOS:A1996UV92000030 PM 8670820 ER PT J AU Law, MG Rosenberg, PS McDonald, A Kaldor, JM AF Law, MG Rosenberg, PS McDonald, A Kaldor, JM TI Age-specific HIV incidence among homosexually active men in Australia SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Article ID CUBIC MILLIMETER; INFECTION; ZIDOVUDINE AB Objective: To estimate age at HIV infection among homosexually active men in Australia. Design: Age-specific back-projection estimates of HIV incidence. Methods: Monthly counts of AIDS among homosexually active men diagnosed by 30 June 1994 and reported by 31 March 1995 were obtained from the National AIDS Registry and were adjusted for reporting delays. The progression rate to AIDS was estimated from a large cohort study of HIV-infected homosexual men, with adjustment for the effect of age at HIV infection and the effect of antiretroviral and prophylactic treatments. Results: The median age at HIV infection was estimated to have decreased from 31 years of age between 1982 and 1984 to between 23 and 27 years in the periods 1987 to 1989 and 1990 to 1994. Despite the trend to a younger median age at HIV infection during the current epidemic, HIV incidence was estimated to have declined in all age groups from a peak in the mid-1980s. This decline was more pronounced in the older age groups, with more modest reductions in age groups under 30 years. Conclusion: Most HIV infections among homosexually active men since 1987 appear to have occurred in men aged under 30 years. This has implications for education programs aimed at preventing HIV infection among homosexually active men. C1 NCI,ROCKVILLE,MD. RP Law, MG (reprint author), UNIV NEW S WALES,NATL CTR HIV EPIDEMIOL & CLIN RES,376 VICTORIA ST,SYDNEY,NSW 2010,AUSTRALIA. RI Kaldor, John /D-4545-2011 NR 19 TC 7 Z9 7 U1 0 U2 0 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD JUN 17 PY 1996 VL 164 IS 12 BP 715 EP 718 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA UU272 UT WOS:A1996UU27200005 PM 8668076 ER PT J AU Herman, EH Zhang, J Chadwick, DP Ferrans, VJ AF Herman, EH Zhang, J Chadwick, DP Ferrans, VJ TI Age dependence of the cardiac lesions induced by minoxidil in the rat SO TOXICOLOGY LA English DT Article DE minoxidil; aging; rat; myocardium; necrosis; inflammation; arteritis; hemorrhage ID HYPOTENSIVE AGENT; DRUG DISPOSITION; MINIATURE SWINE; DOGS; CARDIOTOXICITY; MYOCARDIUM; RESPONSIVENESS; PATHOGENESIS; HYPERTENSION; HEARTS AB To evaluate the age- and dose-dependence of the cardiotoxicity induced by minoxidil, histologic studies were made of the hearts of 3-, 6-, 15- and 24-month-old Sprague Dawley rats treated with either 10, 50 or 250 mg/kg of the drug p.o. daily for two consecutive days. The 10 mg/kg dose of minoxidil induced myocyte necrosis in each of the 24-month-old rats but only in one other animal (6-month-old). The 50 mg/kg dose produced necrosis in all the 15- and 24-month-old rats, but in only one of the other animals (6-month-old), while the 250 mg/kg dose induced necrosis in animals of all ages. Inflammation was present in all minoxidil-treated animals, but at each dose level it was most severe in the oldest rats. Interstitial hemorrhages were observed at all dose levels, but increased in frequency and severity with the dose of minoxidil, and at each dose level they were more severe in the oldest animals. Vascular lesions consisting of arteriolar damage and calcification were observed only in the 24-month-old animals. Thus, these data demonstrate that the cardiac lesions induced by minoxidil are more frequent and severe in older than in younger rats. C1 NHLBI,NIH,PATHOL SECT,BETHESDA,MD 20892. RP Herman, EH (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,HFD 472 MOD 1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 37 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUN 17 PY 1996 VL 110 IS 1-3 BP 71 EP 83 DI 10.1016/0300-483X(96)03337-9 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UQ569 UT WOS:A1996UQ56900008 PM 8658561 ER PT J AU Higgins, M Province, M Heiss, G Eckfeldt, J Ellison, RC Folsom, AR Rao, DC Sprafka, JM Williams, R AF Higgins, M Province, M Heiss, G Eckfeldt, J Ellison, RC Folsom, AR Rao, DC Sprafka, JM Williams, R TI NHLBI Family Heart Study: Objectives and design SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE coronary heart disease; genetics; hypertension; risk factors ID DISEASE; PEDIGREES; CORONARY; UTAH; HYPERTENSION; HISTORY; RISK AB The NHLBI Family Heart Study is a multicenter, population-based study of genetic and nongenetic determinants of coronary heart disease (CHD), atherosclerosis, and cardiovascular risk factors. In phase I, 2,000 randomly selected participants and 2,000 with family histories of CHD were identified among 14,592 middle-aged participants in epidemiologic studies. Medical histories from these individuals, their parents, and their siblings were used to calculate family risk scores that compared the number of reported and validated CHD events with the number expected based on the size, sex, and age of family members. A total of 657 families with the highest risk scores and early-onset CHD and 588 randomly sampled families had clinic examinations that included electrocardiograms, carotid artery ultrasound scans, spirometry, measurements of body size, blood pressure, lipids, lipoproteins, hemostatic factors, insulin, glucose, and routine chemistries. Additional biochemical and genetic studies are being performed on selected participants. Serum, plasma, lymphocytes, red cells, and DNA are stored for future studies, including genotyping of candidate genes and anonymous markers. Contributions of genes, shared and individual environments, and behaviors to variations in risk factors, preclinical atherosclerosis, and CHD will be estimated. Linkage studies, including the quantitative trait loci approach, are planned. C1 WASHINGTON UNIV,SCH MED,DIV BIOSTAT,ST LOUIS,MO 63110. NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. BOSTON UNIV,FRAMINGHAM,MA. UNIV UTAH,SALT LAKE CITY,UT. FU NHLBI NIH HHS [N01-HC-25104, N01-HC-25105, N01-HC-25106] NR 24 TC 213 Z9 215 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1996 VL 143 IS 12 BP 1219 EP 1228 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UQ532 UT WOS:A1996UQ53200005 PM 8651220 ER PT J AU Carter, BL Roccella, EJ AF Carter, BL Roccella, EJ TI Preventing CHF is goal of national high blood pressure education program call to action SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 NHLBI,NHBPEP,BETHESDA,MD 20892. RP Carter, BL (reprint author), UNIV COLORADO,HLTH SCI CTR,SCH PHARM,4200 E 9TH AVE,C238,DENVER,CO 80262, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUN 15 PY 1996 VL 53 IS 12 BP 1381 EP & PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UR395 UT WOS:A1996UR39500001 PM 8781682 ER PT J AU DAquila, RT Hughes, MD Johnson, VA Fischl, MA Sommadossi, JP Liou, SH Timpone, J Myers, M Basgoz, N Niu, M Hirsch, MS Costanzo, L Ruben, S Berzins, B Martinez, A Fishman, I Kazial, K Cort, SN Robinson, P Hall, D Macy, H McLaren, C Rooney, J Warwick, J CavailleColl, M Valentine, F Booth, D Soeiro, R Stein, D Zingman, B Schliosberg, J Polsky, B Sepkowitz, K Sharpe, V Giordano, M Wanke, C Gulick, R Craven, D Grodman, C Fife, K Black, J Todd, K Nixon, H Sperber, K Gerits, P Mildvan, D Nicholas, P Murphy, RL Kessler, H Pulvirenti, J Squires, K Saag, M Weingarten, J Gnann, J Havlir, D Fegan, C Spector, S Richman, D Jacobson, M Dybeck, K Joseph, P Clanon, K McKenzie, S Daniel, P Dayton, D Leonard, J Schooley, R Kuritzkes, D Ray, G Putnam, B Jayaweera, D PatroneReese, J Tanner, T Moebus, J Reed, N StJacque, R Henry, K Swindells, S Eron, J Ragan, D Horton, J Lane, T Frank, I Norris, A Pomerantz, R Hauptman, S Geiseler, J Leedom, J Canchola, F Olson, C Deyton, L Pettinelli, C AF DAquila, RT Hughes, MD Johnson, VA Fischl, MA Sommadossi, JP Liou, SH Timpone, J Myers, M Basgoz, N Niu, M Hirsch, MS Costanzo, L Ruben, S Berzins, B Martinez, A Fishman, I Kazial, K Cort, SN Robinson, P Hall, D Macy, H McLaren, C Rooney, J Warwick, J CavailleColl, M Valentine, F Booth, D Soeiro, R Stein, D Zingman, B Schliosberg, J Polsky, B Sepkowitz, K Sharpe, V Giordano, M Wanke, C Gulick, R Craven, D Grodman, C Fife, K Black, J Todd, K Nixon, H Sperber, K Gerits, P Mildvan, D Nicholas, P Murphy, RL Kessler, H Pulvirenti, J Squires, K Saag, M Weingarten, J Gnann, J Havlir, D Fegan, C Spector, S Richman, D Jacobson, M Dybeck, K Joseph, P Clanon, K McKenzie, S Daniel, P Dayton, D Leonard, J Schooley, R Kuritzkes, D Ray, G Putnam, B Jayaweera, D PatroneReese, J Tanner, T Moebus, J Reed, N StJacque, R Henry, K Swindells, S Eron, J Ragan, D Horton, J Lane, T Frank, I Norris, A Pomerantz, R Hauptman, S Geiseler, J Leedom, J Canchola, F Olson, C Deyton, L Pettinelli, C TI Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection - A randomized, double-blind, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMBINATION THERAPY; MULTIDRUG-RESISTANCE; REPLICATION; INHIBITION; INTERFERON AB Objective: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. Design: A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. Patients: 398 adults who had HIV-1 infection, had 350 or fewer CD4(+) T lymphocytes/mm(3), and had had more than 6 months of previous nucleoside therapy. Intervention: 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing greater than or equal to 60 kg). Measurements: CD4(+) T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA; HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. Results: After 48 weeks of study treatment, the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% CI, 7% to 29%; P = 0.001), a 0.32 log(10) lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (CI, 0.05 to 0.59 log(10) infectious units per million cells; P = 0.023), and a 0.25 log(10) lower mean plasma HIV-1 RNA level (CI, 0.03 to 0.48 log(10) RNA copies/mL; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [CI, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference. Conclusions: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens. C1 AIDS CLIN TRIALS GRP OPERAT OFF,ROCKVILLE,MD. NORTHWESTERN UNIV,CHICAGO,IL 60611. NIAID,PHARMACEUT & REGULATORY AFFAIRS BRANCH,BETHESDA,MD 20892. FRONTIER SCI & TECHNOL RES FDN INC,STAT & DATA MANAGEMENT CTR,AMHERST,MA. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. GLAXO WELLCOME CO,RES TRIANGLE PK,NC. US FDA,BETHESDA,MD 20014. NYU,MED CTR,NEW YORK,NY. CLIN SITE MONITORING GRP,DURHAM,NC. ALBERT EINSTEIN COLL MED,NEW YORK,NY. CORNELL UNIV,NEW YORK,NY. BOSTON CITY HOSP,BOSTON,MA 02118. INDIANA UNIV,INDIANAPOLIS,IN 46204. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CINCINNATI,CINCINNATI,OH. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. UNIV MIAMI,MIAMI,FL 33152. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV PENN,PHILADELPHIA,PA 19104. UNIV SO CALIF,LOS ANGELES,CA. NIAID,DIV AIDS,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,AIDS CLIN TRIALS GRP STAT DATA & ANAL CTR,BOSTON,MA 02115. UNIV ALABAMA,SCH MED,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. UNIV MIAMI,SCH MED,DEPT MED,MIAMI,FL 33101. UNIV ALABAMA,DEPT PHARMACOL,DIV CLIN PHARMACOL,SCH MED,BIRMINGHAM,AL 35294. GENENTECH INC,DEPT BIOSTAT,S SAN FRANCISCO,CA 94080. GEORGETOWN UNIV,MED CTR,DEPT MED,DIV INFECT DIS,WASHINGTON,DC 20007. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. US FDA,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD 20852. OI Murphy, Robert/0000-0003-3936-2052 NR 46 TC 234 Z9 237 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1996 VL 124 IS 12 BP 1019 EP 1030 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA UQ658 UT WOS:A1996UQ65800001 PM 8633815 ER PT J AU Holland, SM Farber, JM Gallin, JI AF Holland, SM Farber, JM Gallin, JI TI Interferon-gamma and management of infectious diseases - Reply SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP Holland, SM (reprint author), NIAID,NATL INST HLTH,9000 ROCKVILLE PIKE,BETHESDA,MD 20189, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1996 VL 124 IS 12 BP 1095 EP 1096 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UQ658 UT WOS:A1996UQ65800014 ER PT J AU Jiang, JJ Liu, KJ Jordan, SJ Swartz, HM Mason, RP AF Jiang, JJ Liu, KJ Jordan, SJ Swartz, HM Mason, RP TI Detection of free radical metabolite formation using in vivo EPR spectroscopy: Evidence of rat hemoglobin thiyl radical formation following administration of phenylhydrazine SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE in vivo; EPR; ESR; spin trapping; phenylhydrazine; free radical ID LIPID-PEROXIDATION; INVIVO; SPECTROMETER AB The spin-trapping technique in conjunction with a low-frequency electron paramagnetic (or spin) resonance (EPR or ESR) spectrometer was used to detect the hemoglobin thiyl free radical in living rats using a whole body resonator. The hemoglobin thiyl free radical was formed following the intragastric administration of phenylhydrazine at the LD(50) dose of 188 mg/kg. The hemoglobin thiyl free radical was then trapped by preinjected 5,5-dimethyl-1-pyrroline N-oxide (DMPO), which formed the DMPO/hemoglobin thiyl-free radical adduct in the blood. The time course of the in vivo formation and disappearance of the spin adduct was followed. The DMPO/hemoglobin thiyl free radical was detected in blood samples using 9.5 GHz (X-band) and 1.1 GHz (L-band) EPR at room temperature and 77 H. Pretreatment of rats with ascorbate and diethylmaleate (DEM) decreased the signal intensity of the DMPO/hemoglobin thiyl free radical spin adduct. The incubation of ascorbate or DEM at 37 degrees C with rat blood containing preformed DMPO/hemoglobin thiyl radical adduct showed that there was no effect of DEM. on the free radical concentration, while ascorbate reduced the radical adduct. This study provided direct evidence of the formation of the DMPO/hemoglobin thiyl free radical in vivo and enabled us to study this formation in living animals free of any artifacts that can occur when using ex vivo methods. (C) 1996 Academic Press, Inc. C1 DARTMOUTH COLL SCH MED,DEPT RADIOL,HANOVER,NH 03755. RP Jiang, JJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,NATL INST HLTH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 27 Z9 28 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 15 PY 1996 VL 330 IS 2 BP 266 EP 270 DI 10.1006/abbi.1996.0252 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV566 UT WOS:A1996UV56600006 PM 8660655 ER PT J AU Chulada, PC Loftin, CD Winn, VD Young, DA Tiano, HF Eling, TE Langenbach, R AF Chulada, PC Loftin, CD Winn, VD Young, DA Tiano, HF Eling, TE Langenbach, R TI Relative activities of retrovirally expressed murine prostaglandin synthase-1 and -2 depend on source of arachidonic acid SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE inducible prostaglandin synthase; constitutive prostaglandin synthase; endogenous arachidonic acid; exogenous arachidonic acid; retroviral expression; murine embryo fibroblasts; Chinese hamster ovary cells ID ENDOPEROXIDE SYNTHASE; G/H SYNTHASE; GENE-TRANSFER; CDNA CLONING; H SYNTHASE; CELLS; CYCLOOXYGENASE; PROTEIN; IDENTIFICATION; FIBROBLASTS AB We have developed derivatives of mouse embryonic fibroblasts (10T1/2) and Chinese hamster ovary (AS52) cells that stably express high levels of murine prostaglandin synthase-l or -2 (PGHS-1 or -2), The cDNAs were transferred using retroviral vectors and the resulting G418-resistant clones were analyzed for prostaglandin E(2) (PGE(2)) production. Specific expression was confirmed by Western and Northern analyses. Enzyme activities, protein, and message levels peaked 1 (10T1/2) or 2 (AS52) days after seeding but decreased as cells became density arrested. Upon subculturing, enzyme activities returned to their initial high levels. With 10 mu M exogenous arachidonic acid (AA) as the substrate, PGHS-1 activities were approximately 3- to B-fold higher than PGHS-2 activities, Conversely, when exogenous AA was left out of the medium and only endogenous AA was available as substrate, enzyme activities were lower; but PGHS-2 activities were 5-fold (10T1/2) or 1.5-fold (AS52) higher than PGHS-1 activities. Following phorbol ester treatment to stimulate endogenous AA release, PGHS-2 activities increased over time and by 6 hours, were 4-fold (10T1/2) or a-fold (AS52) higher than PGHS-1 activities. However, when calcium ionophore A23187 was used to stimulate endogenous AA release, maximum PGHS activities occurred within 30 min of treatment; PGHS-1 activities were equal to (10T1/2) or a-fold higher (AS52) than PGHS-2 activities, Because these cell lines allow us to measure specific PGHS activity in intact cells, we were able to demonstrate that the relative activities of the two PGHS isozymes depend on the source of AA (exogenous versus endogenous) or biochemical stimulus used to mobilize endogenous AA (A23187 versus phorbol ester). These data suggest that PGHS-1 and PGHS-2 preferentially utilize different pools of AA and may be modulated through different stimulus-initiated pathways. (C) 1996 Academic Press, Inc. C1 N CAROLINA STATE UNIV, DEPT TOXICOL, RALEIGH, NC 27695 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. UNIV ROCHESTER, SCH MED & DENT, ROCHESTER, NY 14642 USA. NR 70 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 15 PY 1996 VL 330 IS 2 BP 301 EP 313 DI 10.1006/abbi.1996.0257 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV566 UT WOS:A1996UV56600011 PM 8660660 ER PT J AU Loftin, CD Eling, TE AF Loftin, CD Eling, TE TI Prostaglandin synthase 2 expression in epidermal growth factor-dependent proliferation of mouse keratinocytes SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE epidermal growth factor; prostaglandins; prostaglandin synthase 2; arachidonic acid; linoleic acid; HODE; keratinocytes; mitogenesis ID ARACHIDONIC-ACID METABOLISM; SWISS 3T3 CELLS; MESSENGER-RNA; ENDOPEROXIDE SYNTHASE; LINOLEIC-ACID; H-SYNTHASE; MITOGENIC RESPONSE; PSORIATIC SKIN; POTENTIAL ROLE; G/H SYNTHASE AB BALB/c mouse keratinocytes (BALB/MK) are nontumorigenic epithelial cells which are dependent on mouse epidermal growth factor (EGF) for maintaining proliferation in culture, In BALB/MK the oxygenation of both arachidonic acid and linoleic acid was dependent on EGF. EGF stimulated the formation of prostaglandin E(2) and prostaglandin F-2 alpha from arachidonic acid and 9- and 13-hydroxyoctadecadienoic acid (HODE) from linoleic acid, Analysis of the linoleic acid metabolites determined the ratio of 9-HODE to 13-HODE was approximately 6 to 4, and the 9-HODE was the (R) enantiomer, consistent with metabolism by prostaglandin G/H synthase (PGHS). The formation of these linoleic acid metabolites was sensitive to indomethacin, a PGHS inhibitor. EGF induced the expression of PGHS-2 mRNA after 30 min, which peaked after 1 h, and remained expressed for at least 24 h after the addition of EGF. A less significant increase in the expression of PGHS-1 mRNA occurred 4 h after EGF stimulation, Immunoblot analysis did not detect expression of PGHS-1 protein. However, PGHS-2 protein expression was increased 2 h after EGF exposure and was dependent on EGF. PGHS-2 protein was not transiently expressed as reported with other cell types, but was continually expressed in proliferating cells maintained with EGF at a subconfluent density, Indomethacin significantly attenuated EGF-dependent mitogenesis and cell proliferation. These results suggest that PGHS-2 activity contributes to the proliferative response of BALB/MK to EGF. (C) 1996 Academic Press, Inc. C1 NIEHS,MOLEC BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. NR 51 TC 20 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 15 PY 1996 VL 330 IS 2 BP 419 EP 429 DI 10.1006/abbi.1996.0271 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV566 UT WOS:A1996UV56600025 PM 8660674 ER PT J AU Srivastava, M ZhangKeck, ZY Caohuy, H McPhie, P Pollard, HB AF Srivastava, M ZhangKeck, ZY Caohuy, H McPhie, P Pollard, HB TI Novel isoforms of synexin in Xenopus laevis: Multiple tandem PGQM repeats distinguish mRNAs in specific adult tissues and embryonic stages SO BIOCHEMICAL JOURNAL LA English DT Article ID ADRENAL CHROMAFFIN CELLS; CALCIUM-CHANNEL ACTIVITY; ANNEXIN-VII SYNEXIN; MEMBRANE-FUSION; SECRETION; IDENTIFICATION; GRANULES; OOCYTES; GENE AB Synexin (annexin VII) is a calcium-dependent, phospholipid-binding and membrane fusion protein in the annexin gene family, which forms calcium channels and may play a role in exocytotic secretion. We report here the cloning and characterization of five novel isoforms of cDNAs encoding Xenopus synexin from brain, oocyte and stage 24 cDNA libraries. The most prevalent Xenopus synexin has 1976 bp of cDNA sequence, which contains a 1539 bp open reading frame of 512 amino acids encoding a 54 kDa protein. This Xenopus protein is 6 kDa larger than the previously reported human and mouse synexins with which it shares approx. 73% identity in the C-terminal region and approx. 44% identity in the N-terminal region. Further studies with PCR revealed the molecular basis of the substantial divergence in the Xenopus synexin's N-terminal domain. The domain equivalent to the mammalian tissue-specific cassette exon occurs at a different position and is variable in size and sequence. The most interesting observation relates to the occurrence of different forms of synexin due to the varying numbers of tandem PGQM repeats that are expressed differently in different adult tissues and embryonic stages. For these reasons we have labelled this set of unique isoforms annexin VIIb, referring to mammalian forms, which lack the PGQM tandem repeats, as annexin VIIa. In spite of these differences from annexin VIIa, the form of recombinant annexin VIIb with three PGQM repeats was found to be catalytically active. We interpret these results to indicate that the actual calcium and phospholipid binding sites are conserved in Xenopus, and that the variations observed between members of the synexin gene family in the regulatory domain clearly point towards the tissue- and stage-specific roles of individual members, possibly involving the exocytotic process. C1 NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. RP Srivastava, M (reprint author), NIDDKD,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892, USA. NR 25 TC 8 Z9 9 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1996 VL 316 BP 729 EP 735 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV483 UT WOS:A1996UV48300006 PM 8670145 ER PT J AU Abdullah, LH Davis, SW Burch, L Yamauchi, M Randell, SH Nettesheim, P Davis, CW AF Abdullah, LH Davis, SW Burch, L Yamauchi, M Randell, SH Nettesheim, P Davis, CW TI P-2u purinoceptor regulation of mucin secretion in SPOC1 cells, a goblet cell line from the airways SO BIOCHEMICAL JOURNAL LA English DT Article ID PLATELET-ACTIVATING-FACTOR; EPITHELIAL-CELLS; MUCUS GLYCOPROTEINS; CYSTIC-FIBROSIS; DEPENDENT MECHANISM; PRIMARY CULTURE; ATP; RELEASE; EXPRESSION; RECEPTOR AB The SPOC1 cell, a novel goblet cell line derived from rat trachea, was tested for its ability to exhibit regulated mucin secretion in response to purinergic (P-2) agonists. High-molecular-mass glycoconjugates (HMMGs) purified by CsCl-density-gradient centrifugation had a buoyant density of 1.45 g/ml, The purified HMMG material exhibited a single major band with an apparent molecular mass of greater than 1000 kDa in SDS/polyacrylamide gels stained with silver or blotted and stained with soya-bean agglutinin, [H-3]HMMG was resistant to proteoglycan-degrading enzymes, but was susceptible to neuraminidase. The HMMG was approx. 91% carbohydrate by weight, and the glycosides were O-linked. The HMMG amino acid composition was enriched in Ser and Thr (sum 27%), Thus SPOC1-cell HMMG possess the characteristics of mucin, Mucin secretion by SPOC1 cells, grown on permeable supports and perfused luminally, was stimulated by ATP, UTP and adenosine 5'-[gamma-thio]triphosphate (100 mu M) 4-5-fold over a baseline of 4 ng/min, The three dose-effect relations were nearly identical (K-0.5 similar to 4 mu M). SPOC1 cells grown on plastic and rat tracheal epithelial primary cells responded similarly to ATP and/or UTP, SPOC1 cells failed to respond to other purinergic agonists, either luminally or serosally, and consequently seem to possess an apical membrane P-2u purinoceptor. SPOC1-cell total RNA was probed for P-2u purinoceptor mRNA. Using conserved primers for both reverse transcriptase and PCR, a single band of the predicted size was observed, which had a nucleotide base sequence identical with the rat P-2u purinoceptor mRNA. Thus SPOC1 cells secrete mucin under the control of a P-2u purinoceptor; they should prove useful in dissecting the associated cellular regulatory pathways. C1 UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27514. UNIV N CAROLINA,DEPT PHYSIOL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,DENT RES CTR,CHAPEL HILL,NC 27514. NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. FU NIDCR NIH HHS [DE10489] NR 36 TC 57 Z9 58 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1996 VL 316 BP 943 EP 951 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV483 UT WOS:A1996UV48300035 PM 8670174 ER PT J AU Cheson, BD Bennett, JM Grever, M Kay, N Keating, MJ OBrien, S Rai, KR AF Cheson, BD Bennett, JM Grever, M Kay, N Keating, MJ OBrien, S Rai, KR TI National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment SO BLOOD LA English DT Article ID RETINOBLASTOMA GENE; FLUDARABINE; AGENT; PREDNISONE; EXPRESSION; SURVIVAL RP Cheson, BD (reprint author), NCI,EXECUT PLAZA N,ROOM 741,BETHESDA,MD 20892, USA. NR 38 TC 1433 Z9 1462 U1 3 U2 19 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1996 VL 87 IS 12 BP 4990 EP 4997 PG 8 WC Hematology SC Hematology GA UQ709 UT WOS:A1996UQ70900008 PM 8652811 ER PT J AU Allman, D Jain, A Dent, A Maile, RR Selvaggi, T Kehry, MR Staudt, LM AF Allman, D Jain, A Dent, A Maile, RR Selvaggi, T Kehry, MR Staudt, LM TI BCL-6 expression during B-cell activation SO BLOOD LA English DT Article ID NF-KAPPA-B; FINGER ENCODING GENE; LYMPHOCYTES-B; TRANSLOCATIONS; SEPARATION; LYMPHOMAS; INFECTION; PATHWAYS AB Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma, Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner, The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA, Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a fivefold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 mRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms, These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression, (C) 1996 by The American Society of Hematology. C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. BOEHRINGER INGELHEIM PHARMACEUT INC,DEPT IMMUNOL DIS,RIDGEFIELD,CT. NR 55 TC 203 Z9 210 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1996 VL 87 IS 12 BP 5257 EP 5268 PG 12 WC Hematology SC Hematology GA UQ709 UT WOS:A1996UQ70900038 PM 8652841 ER PT J AU Waldmann, TA Nelson, DL White, JD AF Waldmann, TA Nelson, DL White, JD TI Radioimmunotherapy: Promising treatment of aggressive adult T-cell leukemia? Response SO BLOOD LA English DT Letter ID INTERLEUKIN-2; RECEPTOR RP Waldmann, TA (reprint author), NCI,METAB BRANCH,NIH,BETHESDA,MD 20892, USA. NR 5 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 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1996 VL 87 IS 12 BP 5379 EP 5380 PG 2 WC Hematology SC Hematology GA UQ709 UT WOS:A1996UQ70900051 ER PT J AU Temeck, BK Liebmann, JE Theodossiou, C Steinberg, SM Cook, JA Metz, DC Shawker, TH Allegra, CJ Russo, A Pass, HI AF Temeck, BK Liebmann, JE Theodossiou, C Steinberg, SM Cook, JA Metz, DC Shawker, TH Allegra, CJ Russo, A Pass, HI TI Phase II trial of 5-fluorouracil, leucovorin, interferon-alpha-2a, and cisplatin as neoadjuvant chemotherapy for locally advanced esophageal carcinoma SO CANCER LA English DT Article DE neoadjuvant chemotherapy; esophageal carcinoma; interferon ID SQUAMOUS-CELL CARCINOMA; ADVANCED COLORECTAL-CARCINOMA; PREOPERATIVE CHEMOTHERAPY; SURGICAL THERAPY; CANCER; RADIOTHERAPY; COMBINATION; MANAGEMENT; SURGERY AB BACKGROUND. Most patients with esophageal carcinoma present with locally advanced disease and a poor prognosis. Surgery or radiation provides palliation for locally advanced esophageal carcinoma. The role of neoadjuvant therapy remains to be defined. We administered neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, interferon-alpha-2a, and ciplastin to 11 patients with locally advanced disease. METHODS. Eleven patients with squamous cell or adenocarcinoma of the esophagus were treated preoperatively with two to three cycles of combination chemotherapy. Nine patients underwent resection with curative intent. RESULTS. Six patients received three cycles of chemotherapy, and five received two. Dose reduction was necessary for two patients. One patient achieved a pathologic complete response, histologically confirmed. Of the eleven patients, two did not undergo surgery because of progressive disease during chemotherapy. Seven of the 9 patients relapsed after surgery and 2 have been disease free for 27 months. CONCLUSIONS. The combination 5-FU, leucovorin, interferon-alpha-2a, and cisplatin administered in a neoadjuvant setting resulted in a median survival of 11.8 months with a median time to relapse of 7 months. (C) American Cancer Society. C1 NCI,NIH,SURG BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIDDK,BETHESDA,MD. NIH,DEPT RADIOL,BETHESDA,MD 20892. NIH,NAVAL MED ONCOL BRANCH,BETHESDA,MD 20892. NR 29 TC 6 Z9 7 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 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1996 VL 77 IS 12 BP 2432 EP 2439 DI 10.1002/(SICI)1097-0142(19960615)77:12<2432::AID-CNCR3>3.3.CO;2-F PG 8 WC Oncology SC Oncology GA UN538 UT WOS:A1996UN53800003 PM 8640689 ER PT J AU Ji, BT Chow, WH Yang, G McLaughlin, JK Gao, RN Zheng, W Shu, XO Jin, F Fraumeni, JF Gao, YT AF Ji, BT Chow, WH Yang, G McLaughlin, JK Gao, RN Zheng, W Shu, XO Jin, F Fraumeni, JF Gao, YT TI The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China SO CANCER LA English DT Article DE smoking; alcohol drinking; green tea drinking; stomach cancer; anatomic subsite; case-control study ID GASTRIC CARDIA; UNITED-STATES; CANCER INCIDENCE; DIET; ADENOCARCINOMA; ESOPHAGUS; TOBACCO; POPULATION; MORTALITY; POLAND AB BACKGROUND. The divergent incidence patterns of gastric cardia and distal stomach cancer may suggest different etiologies. This study examined the role of cigarette smoking, alcohol drinking, and green tea consumption as risk factors for carcinoma by anatomic subsite of stomach. METHODS. Newly-diagnosed stomach carcinoma patients (n = 1124) and frequency-matched population controls (n = 1451) were interviewed in person. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS. Excess risks associated with cigarette smoking and alcohol consumption were observed largely among men. The adjusted ORs for all stomach cancer combined were 1.35 (CI: 1.06-1.71) for current smokers, and 1.26 (CI: 0.86-1.84) for ex-smokers. For rumors of the distal stomach, statistically significant positive dose-response trends were found for the number of cigarettes smoked per day, the duration and pack-years of smoking, and inverse trends for years of stopped smoking. For tumors of the gastric cardia, however, a monotonic association was found only for the number of cigarettes smoked per day (P = 0.06). Alcohol consumption was not related to the risk of cardia cancer, while a moderate excess risk of distal stomach cancer (OR: 1.55; CI: 1.07-2.26) was observed among heavy alcohol drinkers. Green tea drinking was inversely associated with risk of stomach cancer arising from either subsite, with ORs of 0.77 (CI: 0.52-1.13) among female heavy drinkers, and 0.76 (CI: 0.55-1.27) among male heavy drinkers. CONCLUSIONS. Our findings provide further evidence that cigarette smoking and, possibly, alcohol consumption increase the risk of stomach carcinoma, notably of the distal segment. An inverse association with green tea drinking was also observed. (C) 1996 American Cancer Society. C1 COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. ZHEJIANG MED UNIV,ZHEJIANG CANC INST,HANGZHOU,PEOPLES R CHINA. RP Ji, BT (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,6130 EXECUT BLVD,EPN 431,ROCKVILLE,MD 20852, USA. NR 64 TC 126 Z9 134 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1996 VL 77 IS 12 BP 2449 EP 2457 DI 10.1002/(SICI)1097-0142(19960615)77:12<2449::AID-CNCR6>3.0.CO;2-H PG 9 WC Oncology SC Oncology GA UN538 UT WOS:A1996UN53800006 PM 8640692 ER PT J AU Travis, WD Lubin, J Ries, L Devesa, S AF Travis, WD Lubin, J Ries, L Devesa, S TI United states lung carcinoma incidence trends - Declining for most histologic types among males, increasing among females SO CANCER LA English DT Article DE lung carcinoma; sex; race; histologic type; epidemiology; incidence ID DIETARY VITAMIN-A; 18 MAJOR CANCERS; CIGARETTE-SMOKING; ADENOSQUAMOUS CARCINOMA; RISK-FACTORS; PROJECTIONS; MORTALITY; EPIDEMIOLOGY; VEGETABLES; PATTERNS AB BACKGROUND. Lung carcinoma is now the most frequently diagnosed major cancer in the world and is also the most common cause of cancer deaths in males and females in the United States and worldwide. Based on trends in cigarette smoking and on analysis of lung cancel rates by birth cohort, it was predicted that a decline would occur in age-adjusted lung cancer rarest initially in males, and approximately 10 years later in females. We evaluated age-adjusted lung cancer incidence rates for changes in trends by race, sex, and histologic type to determine if and when rates may have started declining. METHODS. We analyzed population-based incidence data from the National Cancer Institute's Third National Cancer Survey conducted between 1969 and 1971 and from the Surveillance, Epidemiology and End-Results (SEER) program conducted between 1974 and 1991. Age-adjusted rates were plotted by lime period using a logarithmic scale for the ordinate. We used regression methods for grouped time-to-response data to fit a model to the disease rare for age, and calendar year to estimate the calendar year of maximum disease rate. RESULTS. During this period, the overall age-adjusted lung cancer incidence rate rose from 37.8 to 68.2 per 100,000. Lung cancer rates in both while and black males climaxed around 1984 and declined subsequently. Furthermore, among white and black males, the rates of squamous cell carcinoma, small cell carcinoma, and large cell carcinoma declined after peaks in 1981 and 1982, 1986 and 1987, and 1986 and 1988, respectively. The rates for adenocarcinoma in black males peaked in 1987 whereas the rates in white males appeared to have plateaued between 1989 and 1991. Total lung cancer rates in males exceeded those in females, with rates in black males exceeding rates in white males. Age-adjusted lung carcinoma rates among white and black females continued to increase for all histologic types, with the exception of large cell carcinoma among whites, bronchioloalveolar carcinoma among whites and blacks, and adenosquamous carcinoma among blacks, CONCLUSIONS. The cumulative effect of these trends has resulted in a plateau of total lung carcinoma incidence in all persons combined, and a decline might be expected soon, as has already been observed among males. Most of these changes reflect past cigarette smoking patterns. Demonstration or declines and tapering increases among several population subgroups suggests impending reductions in the incidence and mortality rate for this highly fatal cancer. (C) 1996 American Cancer Society. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV EPIDEMIOL & GENET,BETHESDA,MD 20892. NCI,SURVEILLANCE EPIDEMIOL & END RESULTS PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Travis, WD (reprint author), ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,NW 14TH ST & ALASKA AVE,WASHINGTON,DC 20306, USA. NR 60 TC 186 Z9 192 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1996 VL 77 IS 12 BP 2464 EP 2470 DI 10.1002/(SICI)1097-0142(19960615)77:12<2464::AID-CNCR8>3.0.CO;2-M PG 7 WC Oncology SC Oncology GA UN538 UT WOS:A1996UN53800008 PM 8640694 ER PT J AU Sadrieh, N Davis, CD Snyderwine, EG AF Sadrieh, N Davis, CD Snyderwine, EG TI N-acetyltransferase expression and metabolic activation of the food-derived heterocyclic amines in the human mammary gland SO CANCER RESEARCH LA English DT Article ID ACETYLATION PHARMACOGENETICS; BREAST-CANCER; PHENOTYPE; MONKEYS; CYTOSOL; MEIQX; PHIP; IQ AB The heterocyclic amines (HCAs) found in cooked meat are procarcinogens that are metabolically activated by N-hydroxylation followed by O-acetylation by the N-acetyltransferases NAT1 and NAT2. Despite the importance of metabolic activation in HCA carcinogenicity and the finding that several HCAs are rodent mammary gland carcinogens, nothing was known about O-acetylation activity in the human mammary gland. The current study examines the expression and catalytic activity of NAT toward the N-hydroxy-HCAs 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) and 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ) in the human mammary gland. Mammary gland cytosol from 10 women and lysates from a primary culture of human mammary epithelial cells metabolically activated 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline by NAT-mediated O-acetyltransferase, as measured by the acetyl CoA-enhanced binding of the N-hydroxylamines to calf thymus DNA in vitro, N-acetylation of p-aminosalicylic, an activity specific to NAT1, but not N-acetylation of sulfamethazine, an activity specific to NAT2, was detected in the mammary gland cytosols and human mammary epithelial cell lysates. Immunohistochemical analysis of human mammary gland sections showed positive staining for NAT1 protein in the epithelial cells lining the mammary gland ducts. Reverse transcription-PCR analysis showed that mRNA transcripts for both NAT1 and NAT2 were present in human mammary gland; however, no NAT2 catalytic activity was detectable. Our data demonstrate for the first time that the human mammary gland is catalytically active toward the metabolic activation of HCA food mutagens, and that this activity is most likely contributed by NAT1 expressed in the ductular epithelial cells of the mammary gland. RP Sadrieh, N (reprint author), NCI, EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28, 37 CONVENT DR, MSC4255, BETHESDA, MD 20892 USA. NR 25 TC 76 Z9 77 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1996 VL 56 IS 12 BP 2683 EP 2687 PG 5 WC Oncology SC Oncology GA UP665 UT WOS:A1996UP66500002 PM 8665493 ER PT J AU Xie, H Notkins, AL Lan, MS AF Xie, H Notkins, AL Lan, MS TI IA-2, a transmembrane protein tyrosine phosphatase, is expressed in human lung cancer cell lines with neuroendocrine phenotype SO CANCER RESEARCH LA English DT Article ID CYTOGENETIC ABNORMALITIES; SUPPLEMENTED MEDIUM; ENDOCRINE-CELLS; CHROMOGRANIN-A; CARCINOMA; GROWTH; DIFFERENTIATION; TUMORS AB IA-2 is a transmembrane protein tyrosine phosphate isolated recently from a human insulinoma subtraction library. Its expression in normal human tissues is restricted primarily to the pancreatic islets and brain. In this report, we describe the expression of IA-2 mRNA in a panel consisting of 20 lung tumor cell lines with neuroendocrine and non-neuroendocrine phenotype and 17 non-lung tumor cell lines. IA-2 nRNA was detected in 8 of 11 neuroendocrine small cell lung carcinomas, 4 of 4 non-small cell lung carcinomas with neuroendocrine phenotype, and 11 of 12 non-lung neuroendocrine tumor cell lines. In contrast, IA-2 mRNA was not detected in five non-neuroendocrine lung carcinomas, nor in a panel of other non-neuroendocrine tumor cell lines. The expression pattern of IA-2 mRNA suggests that IA-2 may represent a new marker for neuroendocrine differentiation in human lung cancer cells and perhaps other neuroendocrine tumors. C1 NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. NR 28 TC 19 Z9 19 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1996 VL 56 IS 12 BP 2742 EP 2744 PG 3 WC Oncology SC Oncology GA UP665 UT WOS:A1996UP66500015 PM 8665506 ER PT J AU Chamberlain, RS Carroll, MW Bronte, V Hwu, P Warren, S Yang, JC Nishimura, M Moss, B Rosenberg, SA Restifo, NP AF Chamberlain, RS Carroll, MW Bronte, V Hwu, P Warren, S Yang, JC Nishimura, M Moss, B Rosenberg, SA Restifo, NP TI Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines SO CANCER RESEARCH LA English DT Article ID EXPRESSION; ANTIGEN; VIRUSES; LIGAND; CTLA-4; CD28 AB Activation of T lymphocytes in the absence of a costimulatory signal can results in anergy or apoptotic cell death. Two molecules capable of providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have been shown to augment the immunogenicity of whole-tumor cell vaccines. To explore a potential role for costimulation in the design of recombinant anticancer vaccines, we used lacZ-transduced CT26 as an experimental tumor and beta-galactosidase (beta-gal) as the model tumor antigen. Attempts to augment the function of a recombinant vaccinia virus (rVV) expressing beta-gal by admixture wit rVV expressing murine B7-1 were unsuccessful. However, a double recombinant vaccinia virus engineered to express both B7-1 and the model antigen beta-gal was capable of significantly reducing the number of pulmonary metastases when administered to mice bearing tumors established for 3 or 6 days. Most important, the double recombinant vaccinia virus prolonged the survival of tumor-bearing mice. These effects were antigen specific. The related costimulatory molecule B7-2 was found to have a similar, although less impressive enhancing effect on the function of a rVV expressing beta-gal. Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV encoding a model antigen significantly enhanced the therapeutic antitumor effects of these poxvirus-based, therapeutic anticancer vaccines. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 20 TC 78 Z9 80 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1996 VL 56 IS 12 BP 2832 EP 2836 PG 5 WC Oncology SC Oncology GA UP665 UT WOS:A1996UP66500031 PM 8665522 ER PT J AU Caracciolo, EA Chaitman, BR Forman, SA Stone, PH Bourassa, MG Sopko, G Geller, NL Conti, CR AF Caracciolo, EA Chaitman, BR Forman, SA Stone, PH Bourassa, MG Sopko, G Geller, NL Conti, CR TI Diabetics with coronary disease have a prevalence of asymptomatic ischemia during exercise treadmill testing and ambulatory ischemia monitoring similar to that of nondiabetic patients - An ACIP database study SO CIRCULATION LA English DT Article DE diabetes mellitus; coronary disease; ischemia; exercise ID SILENT-MYOCARDIAL-ISCHEMIA; ANGINAL PERCEPTUAL THRESHOLD; AUTONOMIC NEUROPATHY; ARTERY DISEASE; HEART-DISEASE; STABLE ANGINA; CARDIOVASCULAR-DISEASE; NECROPSY PATIENTS; NOCTURNAL ANGINA; OXYGEN-DEMAND AB Background There are conflicting data as to whether diabetics have a higher prevalence of asymptomatic ST-segment depression during exercise treadmill testing (ETT) and ambulatory ECG (AECG) monitoring. This study was conducted to determine whether diabetic patients with coronary disease enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) have more episodes of asymptomatic ischemia during ETT and 48-hour AECG monitoring than nondiabetic patients and to compare differences in angiographic variables and the magnitude of ischemia as measured by standard ETT and AECG criteria. Methods and Results Angiographic variables and the prevalence and magnitude of ischemia during the qualifying ETT and 48-hour AECG were compared by the presence and absence of diabetes mellitus in 558 randomized ACIP patients. Seventy-seven patients had a history of diabetes and were taking oral hypoglycemics or insulin (diabetic group); 481 patients did not meet these criteria (nondiabetic group). Multivessel disease (87% versus 74%, P=.01) was more frequent in the diabetic group. The percentages of patients without angina during the ETT were similar in the diabetic and nondiabetic groups (36% and 39%, respectively). Time to onset of greater than or equal to 1-mm ST-segment depression and time to onset of angina were similar in both groups. The percentages of patients with only asymptomatic ST-segment depression during the 48-hour AECG were similar in the diabetic and nondiabetic groups (94% versus 88%, respectively). However, total ischemic time per 24 hours (15.0+/-21.4 versus 23.6+/-31.1 minutes, P=.02), ischemic time per episode (6.3+/-4.6 versus 9.0+/-8.7 minutes, P<.01), and the maximum depth of ST-segment depression tended to be less in the diabetic group. Conclusions Patients enrolled in ACIP were selected on the basis of an abnormal ETT and 48-hour AECG and ability to undergo coronary revascularization. When patients with diabetes mellitus were compared with those without diabetes, there was a similar prevalence of asymptomatic ischemia during ETT and 48-hour AECG monitoring. Despite more extensive and diffuse coronary disease, diabetic ACIP patients tended to have less measurable ischemia during the 48-hour AECG. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. ST LOUIS UNIV,HLTH SCI CTR,ST LOUIS,MO. NHLBI,BETHESDA,MD 20892. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. UNIV FLORIDA,GAINESVILLE,FL. RP Caracciolo, EA (reprint author), MARYLAND MED RES INST,ACIP,CLIN COORDINATING CTR,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HV-90-08, HV-90-07, HV-91-05] NR 55 TC 46 Z9 50 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 15 PY 1996 VL 93 IS 12 BP 2097 EP 2105 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UQ399 UT WOS:A1996UQ39900003 PM 8925577 ER PT J AU Beckner, ME Krutzsch, HC Klipstein, S Williams, ST Maguire, JE Doval, M Liotta, LA AF Beckner, ME Krutzsch, HC Klipstein, S Williams, ST Maguire, JE Doval, M Liotta, LA TI AAMP, a newly identified protein, shares a common epitope with alpha-actinin and a fast skeletal muscle fiber protein SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN PARTICLE; BETA-SUBUNITS; ANTIGENIC DETERMINANTS; SACCHAROMYCES-CEREVISIAE; HUMAN NEUTROPHILS; BINDING DOMAIN; YEAST; GENE; HOMOLOGY; SEQUENCE AB AAMP (angio-associated migratory cell protein) shares a common epitope with alpha-actinin and a fast-twitch skeletal muscle fiber protein. An antigenic peptide, P189, derived from the sequence of AAMP was synthesized. Polyclonal antibodies generated to P189 readily react with AAMP (52 kDa) in brain and activated T lymphocyte lysates, alpha-actinin (100 kDa) in all tissues tested, and a 23-kDa protein in skeletal muscle lysates. The antibody's reactivity for alpha-actinin can be competed with the purified protein. Activation of T lymphocytes does not alter the degree of Lu-actinin reactivity with anti-P189 as it does for AAMP's reactivity in these lysates. Competition studies with peptide variants show that six amino acid residues, ESESES, constitute a common epitope in all three proteins in human tissues. The antigenic determinant is continuous in AAMP but discontinuous (or assembled) in alpha-actinin. alpha-Actinin does not contain this epitope in its linear sequence so reactivity is attributed to an epitope formed by its secondary structure. Limited digestion of the reactive proteins with thermolysin destroys anti-P189's reactivity for alpha-actinin while reactivity for recombinant AAMP is retained. Specificity of anti-P189 for human skeletal muscle fast fibers seen on immunoperoxidase staining may be explained by anti-P189's reactivity with a 23-kDa protein found only in skeletal muscle lysates. Its pattern of reactivity is the same as that obtained using monoclonal anti-skeletal muscle myosin heavy chain in type II (fast-twitch) fibers. (C) 1996 Academic Press, Inc. C1 WASHINGTON HOSP CTR,WASHINGTON,DC 20010. RP Beckner, ME (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,RM 2A-33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 54 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 15 PY 1996 VL 225 IS 2 BP 306 EP 314 DI 10.1006/excr.1996.0181 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UU965 UT WOS:A1996UU96500010 PM 8660919 ER PT J AU Kieser, A Seitz, T Adler, HS Coffer, P Kremmer, E Crespo, P Gutkind, JS Henderson, DW Mushinski, JF Kolch, W Mischak, H AF Kieser, A Seitz, T Adler, HS Coffer, P Kremmer, E Crespo, P Gutkind, JS Henderson, DW Mushinski, JF Kolch, W Mischak, H TI Protein kinase C-zeta reverts v-raf transformation of NIH-3T3 cells SO GENES & DEVELOPMENT LA English DT Article DE protein kinase C-zeta; v-raf; suppression of transformation; junB induction; egr-1 induction; junB promoter ID NIH 3T3 CELLS; SUBSTRATE-SPECIFICITY; DEPENDENT ACTIVATION; SIGNAL-TRANSDUCTION; SUBSPECIES BLOCKS; EARLY RESPONSE; EXPRESSION; ALPHA; PROMOTER; SEQUENCE AB We have identified protein kinase C-zeta (PKC-zeta) as a novel suppressor of neoplastic transformation caused by the v-raf oncogene. PKC-zeta overexpression drastically retards proliferation, abolishes anchorage-independent growth, and reverts the morphological transformation of v-raf-transformed NIH-3T3 cells. The molecular basis for this effect appears to be a specific induction of junB and egr-1 expression, triggered synergistically by PKC-zeta via a Raf/Mek/MAPK-independent mechanism and v-raf. junB-promoter/CAT assays revealed that PKC-zeta directly targets the junB promoter. The induction of junB and egr-1 is linked to the v-raf transformation-suppressing effect of PKC-zeta as constitutive expression of junB and egr-1 but not of c-jun also abolishes anchorage-independent growth of v-raf-transformed NIH-3T3 cells. Moreover, junB overexpression leads to a retardation of proliferation in these cells. PKC-zeta interferes with the serum inducibility of an AP-1 reporter plasmid in v-raf-transformed NIH-3T3 cells, indicating that PKC-zeta antagonizes transformation and proliferation by down-modulating AP-1 function via induction of junB. In summary, our data suggest that PKC-zeta counteracts v-raf transformation by modulating the expression of the transcription factors junB and egr-1. C1 UNIV UTRECHT HOSP,DEPT PULM DIS,2584 CX UTRECHT,NETHERLANDS. GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT GMBH,INST IMMUNOL,D-81377 MUNICH,GERMANY. NIDR,MOLEC SIGNALING UNIT,NIH,BETHESDA,MD 20892. NCI,MOLEC GENET SECT,GENET LAB,BETHESDA,MD 20892. RP Kieser, A (reprint author), GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT GMBH,INST KLIN MOL BIOL & TUMOR GENET,D-81377 MUNICH,GERMANY. RI Gutkind, J. Silvio/A-1053-2009; Coffer, Paul/A-5769-2009; Mischak, Harald/E-8685-2011; Kieser, Arnd/M-4616-2014; Crespo, Piero/M-3273-2014; Adler, Heiko/M-7355-2014 OI Kieser, Arnd/0000-0003-0783-1950; Crespo, Piero/0000-0003-2825-7783; Adler, Heiko/0000-0002-6481-6709 NR 72 TC 40 Z9 40 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 15 PY 1996 VL 10 IS 12 BP 1455 EP 1466 DI 10.1101/gad.10.12.1455 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UU117 UT WOS:A1996UU11700003 PM 8666230 ER PT J AU Tamimi, R Steingrimsson, E Copeland, NG DyerMontgomery, K Lee, JE Hernandez, R Jenkins, NA Tapscott, SJ AF Tamimi, R Steingrimsson, E Copeland, NG DyerMontgomery, K Lee, JE Hernandez, R Jenkins, NA Tapscott, SJ TI The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2 SO GENOMICS LA English DT Article ID LINKAGE MAP AB The Neurod gene is a basic-helix-loop-helix gene that regulates neurogenesis and is identical to the hamster beta2 gene that was cloned as a regulator of insulin transcription. Here we report the cloning of human NEUROD and mapping of the gene to human chromosome 2q32 and to mouse chromosome 2. (C) 1996 Academic Press, Inc. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV COLORADO,HLTH SCI CTR,DEPT PEDIAT ONCOL,DENVER,CO 80262. NR 12 TC 31 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1996 VL 34 IS 3 BP 418 EP 421 DI 10.1006/geno.1996.0306 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UU191 UT WOS:A1996UU19100018 PM 8786144 ER PT J AU Lafrenie, RM Yamada, KM AF Lafrenie, RM Yamada, KM TI Integrin-dependent signal transduction SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MELANOMA CELL INVASION; FOCAL ADHESION KINASE; EXTRACELLULAR-MATRIX; TYROSINE PHOSPHORYLATION; GENE-EXPRESSION; EMBRYO FIBROBLASTS; ENDOTHELIAL-CELLS; CARCINOMA-CELLS; IV COLLAGENASE AB Integrins are receptor molecules for extracellular matrix molecules (e.g., the beta(1) family), serum components (alpha(v) family) and immunoglobulin family adhesion molecules (beta(2) family). Integrin-dependent adhesion has also been shown to have metabolic consequences. Adhesion to a variety of extracellular matrix proteins, such as fibronectin, collagen, and laminin, is a potent regulator of cell growth, differentiation, and gene expression. Ligand binding or aggregation of integrin receptors initiates a number of metabolic changes including activation of serine/threonine and tyrosine kinases, increased Ca2+ influx, increased cytoplasmic alkalinization, and altered inositol lipid metabolism. In some instances activation of transcription factors and induction of gene expression have also been demonstrated. Components of key signaling pathways involving integrins are beginning to be identified. Some studies have shown that integrins form multi-component complexes with signal transduction molecules. Elucidating the interactions of the signal transduction molecules with each other and with the integrin cytoplasmic domains will be key to understanding the initial events of signal transduction through the integrins. (C) 1996 Wiley-Liss, Inc. RP Lafrenie, RM (reprint author), NIDR,DEV BIOL LAB,DIR,NIH,BLDG 30,RM 408,30 CONVENT DR,MSC-4370,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 69 TC 115 Z9 115 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 15 PY 1996 VL 61 IS 4 BP 543 EP 553 DI 10.1002/(SICI)1097-4644(19960616)61:4<543::AID-JCB7>3.0.CO;2-O PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV224 UT WOS:A1996UV22400007 PM 8806077 ER PT J AU Kishore, BK Mandon, B Oza, NB DiGiovanni, SR Coleman, RA Ostrowski, NL Wade, JB Knepper, MA AF Kishore, BK Mandon, B Oza, NB DiGiovanni, SR Coleman, RA Ostrowski, NL Wade, JB Knepper, MA TI Rat renal arcade segment expresses vasopressin-regulated water channel and vasopressin V-2 receptor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ELISA; RT-PCR; immunocytochemistry; arcades; kidney ID NEPHRON SEGMENTS; COLLECTING DUCT; DISTAL TUBULE; V2 RECEPTOR; KIDNEY; CLONING; ANTIBODIES; HORMONE; LIVER AB The arcades are long, branched renal tubules which connect deep and mid-cortical nephrons to cortical collecting ducts in the renal cortex, Because they are inaccessible by standard physiological techniques, their functions are poorly understood, In this paper, we demonstrate that the arcades are a site of expression of two proteins, aquaporin-2 (the vasopressin-regulated water channel) and the V-2 vasopressin receptor, that are important to regulated water transport in the kidney, Using a peptide-derived polyclonal antibody to aquaporin-2, quantitative ELISA in microdissected segments showed that aquaporin-2 is highly expressed in arcades and that the expression is increased in response to restriction of fluid intake, Immunocytochemistry revealed abundant aquaporin-2 labeling of structures in the cortical labyrinth in a pattern similar to that of the Na+-Ca2+ exchanger and kallikrein, marker proteins expressed in arcades but not in cortical collecting ducts. RT-PCR experiments demonstrated substantial aquaporin-2 and V-2 receptor mRNA in microdissected arcades. In situ hybridization, using S-35-labeled antisense cRNA probes for the V-2 receptor demonstrated strong labeling of both arcades and cortical collecting ducts, Thus, these results indicate that the arcades contain the specific proteins associated with vasopressin-regulated water transport, and may be a heretofore unrecognized site of free water absorption. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. NIMH,LAB BIOL PSYCHIAT,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. FU NIDDK NIH HHS [DK-32839] NR 35 TC 54 Z9 54 U1 0 U2 1 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 JUN 15 PY 1996 VL 97 IS 12 BP 2763 EP 2771 DI 10.1172/JCI118731 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UT429 UT WOS:A1996UT42900013 PM 8675687 ER PT J AU Hengge, UR Walker, PS Vogel, JC AF Hengge, UR Walker, PS Vogel, JC TI Expression of naked DNA in human, pig, and mouse skin SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE epidermis; organ culture; plasmid DNA; gene expression ID BETA-GALACTOSIDASE; MUSCLE; CELLS AB The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epidermis, but also in the dermis and underlying fat and muscle tissue, and is expressed at lower levels, These findings suggest that genes can be expressed in human skin, after injection of naked DNA, and indicate that pig skin is an appropriate model for the study of DNA uptake and gene expression in human skin, The organ cultures of human and pig skin may be useful in understanding how naked DNA is internalized and expressed after in vivo injections. Additionally, skin obtained from patients with skin disease maybe studied as skin grafts and organ cultures to help optimize genetic approaches for the treatment of skin diseases prior to clinical trials, by determining if the injected gene can provide a therapeutic benefit. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 16 TC 155 Z9 158 U1 0 U2 3 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 JUN 15 PY 1996 VL 97 IS 12 BP 2911 EP 2916 DI 10.1172/JCI118750 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UT429 UT WOS:A1996UT42900032 PM 8675706 ER PT J AU Zhong, SB Sharp, DS Grove, JS Bruce, C Yano, K Curb, JD Tall, AR AF Zhong, SB Sharp, DS Grove, JS Bruce, C Yano, K Curb, JD Tall, AR TI Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HDL; CETP; atherosclerosis; coronary heart disease; mutation ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; TRANSGENIC MICE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; PLASMA; METABOLISM; HYPERTRIGLYCERIDEMIA; ATHEROSCLEROSIS; HAWAII AB Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD), The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver, A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A,0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G), However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations, The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008), Similar RR values were obtained for the D442G mutation alone, Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence, Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl, The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i,e,, reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction. C1 COLUMBIA UNIV,DEPT MED,DIV MOLEC MED,NEW YORK,NY 10032. NHLBI,HONOLULU HEART PROGRAM,HONOLULU,HI 96817. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,DIV CLIN EPIDEMIOL,HONOLULU,HI 96817. UNIV HAWAII,SCH PUBL HLTH,HONOLULU,HI 96817. FU NHLBI NIH HHS [HL-21006, HL-22682] NR 40 TC 416 Z9 434 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 JUN 15 PY 1996 VL 97 IS 12 BP 2917 EP 2923 DI 10.1172/JCI118751 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UT429 UT WOS:A1996UT42900033 PM 8675707 ER PT J AU Mackall, CL Bare, CV Granger, LA Sharrow, SO Titus, JA Gress, RE AF Mackall, CL Bare, CV Granger, LA Sharrow, SO Titus, JA Gress, RE TI Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ATHYMIC NUDE RATS; LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; TRANSGENIC MICE; LYMPHOID ORGANS; LIFE-SPAN; RECEPTOR; EXPRESSION; SELECTION; DIFFERENTIATION AB Thymic regenerative capacity in humans decreases with age, suggesting that thymic-independent pathways of T cell regeneration may predominate during adulthood. Using a murine bone marrow transplantation model, we present evidence that thymic-independent T cell regeneration occurs primarily via expansion of peripheral T cells and is Ag driven since significant expansion of CD4(+) or CD8(+) transgenic (Tg(+))/TCR-bearing cells occurs only in the presence of Ag specific for the TCR. Such expansion resulted in skewing of the regenerated repertoire with 40 to 65% of the regenerated CD4(+) or CD8(+) T cells expressing the Tg(+)/TCR in thymectomized hosts after bone marrow transplantation. In experiments in which nontransgenic populations are used as T cell inocula, we noted decreased CD4 expansion when Class II MHC was blocked by mAb treatment in vivo, and CD8 expansion failed to occur in Class I MHC-deficient hosts providing evidence that T cell regeneration in thymic-deficient hosts largely occurs via TCR-MHC-mediated selection of peripheral T cell populations. This process results in a T cell repertoire comprised exclusively of T cells recently activated by the antigenic milieu of the host, with negligible numbers of residual ''naive'' cells bearing TCRs for Ags absent at the time of expansion. These findings have important implications for approaches to enhance T cell regeneration in humans and provide evidence that vaccine strategies could skew the T cell repertoire toward a specific antigenic target if administered to thymic-deficient hosts during immune reconstitution. RP Mackall, CL (reprint author), NCI,EXPTL IMMUNOL BRANCH,NATL INST HLTH,BLDG 10,ROOM 4B14,10 CTR DR,MSC 1360,BETHESDA,MD 20892, USA. NR 48 TC 302 Z9 312 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 JUN 15 PY 1996 VL 156 IS 12 BP 4609 EP 4616 PG 8 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200012 PM 8648103 ER PT J AU Shirakata, Y Shuman, JD Coligan, JE AF Shirakata, Y Shuman, JD Coligan, JE TI Purification of a novel MHC class I element binding activity from thymus nuclear extracts reveals that thymic RBP-J kappa/CBF1 binds to NF-kappa B-like elements SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; MOUSE; GENE; PROTEIN; SEQUENCE AB We purified a DNA binding protein that recognizes a portion of the MHC class I regulatory element region 1/NF-kappa B binding site whose expression correlates with the expression of a MHC class I transgene in the thymus. The N-terminal amino acid sequence and the molecular size matched the RBP-J kappa protein, also known as the EBV C-promoter binding factor, CBF1. Antipeptide sera reactive with RBP-J kappa/CBF1 also reacted with this protein in gel mobility shift assays. Although RBP-J kappa/CBF1 is ubiquitously expressed, binding to the MHC class Ia NF-kappa B site was limited to the thymus. Comparison of the DNA binding specificities of RBP-J kappa/CBF1 in thymic and splenic nuclear extracts revealed strong binding from both extracts to an IFN-beta kappa B site containing the RBP-J kappa/CBF1 consensus sequence (CGTGGGAA). In contrast, only the thymic nuclear extract showed strong DNA binding activity with probes containing the NF-kappa B recognition sequences present in the MHC class Ia, IL-2R alpha, and granulocyte-macrophage CSF promoters. Thus, RBP-J kappa/CBF1 in thymic extracts demonstrates a clearly distinguishable DNA binding specificity that correlates with tissue-specific expression of a class I transgene. This, coupled with the fact that our previous study showed enhanced expression of the transgene in CD4(+)CD8(+) thymocytes, suggests that RBP-J kappa/CBF1 may play a role in the development of the immune system. C1 NIAID,MOLEC STRUCT LAB,NATL INST HLTH,ROCKVILLE,MD 20852. NR 30 TC 16 Z9 16 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 JUN 15 PY 1996 VL 156 IS 12 BP 4672 EP 4679 PG 8 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200021 PM 8648111 ER PT J AU Fogler, WE Volker, K McCormick, KL Watanabe, M Ortaldo, JR Wiltrout, RH AF Fogler, WE Volker, K McCormick, KL Watanabe, M Ortaldo, JR Wiltrout, RH TI NK cell infiltration into lung, liver, and subcutaneous B16 melanoma is mediated by VCAM-1/VLA-4 interaction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; TUMOR-NECROSIS-FACTOR; ADOPTIVELY TRANSFERRED ADHERENT; MIDDLE-T ONCOGENE; ADHESION MOLECULES; RESPONSE MODIFIERS; EXPRESSION; ACTIVATION; MICE AB The mechanisms that regulate the adhesion and migration of NK cells to and across endothelium have been studied under nonflow conditions; however, the involvement of these processes in vivo is poorly understood. The present studies investigated the potential vascular adhesion ligand interactions that determine the in vivo recruitment of NK cells to pulmonary and hepatic parenchyma, and s.c. tumor after treatment of mice with biologic response modifiers. Seventy-two hours after a single injection of the cytokine-inducing agent poly-L-lysine stabilized in carboxylmethyl cellulose (poly-ICLC), pulmonary NK cell lytic activity and N-alpha-carbobenzoxy-L-lysine thiobenzyl ester (BLT)-esterase were augmented 29- and 14-fold, respectively, and the number of lung-associated NK cells was increased from 2.3 x 10(5) to 7.4 x 10(5). Similar fold increases in NK cell number and activity were observed in the liver and s.c. B16 melanoma after poly-ICLC injection or in the lungs and liver of mice treated with IL-2. Concomitant treatment of mice with alpha-VCAM-1 or alpha-VLA-4 mAb, but not alpha-ICAM-1 or alpha-LFA-1, abrogated the poly-ICLC and IL-2-induced increase in organ-associated NK activity and percentage of tumor-associated NK cells, resulted in a 61 to 76% decrease in pulmonary and hepatic NK cell number, and was independent of T and/or B cells. The decrease in NK cell number in organ parenchyma and tumor lesions was correlated to an increase in the number of NK cells in peripheral blood, but not bone marrow. These results demonstrate that VCAM-1/VLA-4 interaction is critically involved in the infiltration of newly recruited NK cells into lung, liver, and progressively growing tumor after mobilization from the bone marrow. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENES & DEV PROGRAM,FREDERICK,MD 21702. RP Fogler, WE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPT THERAPEUT SECT,EXPTL IMMUNOL LAB,DIV BASIC SCI,BLDG 560,FREDERICK,MD 21702, USA. NR 51 TC 89 Z9 90 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1996 VL 156 IS 12 BP 4707 EP 4714 PG 8 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200026 PM 8648116 ER PT J AU Coin, PG Lindroos, PM Bird, GS OsornioVargas, AR Roggli, VL Bonner, JC AF Coin, PG Lindroos, PM Bird, GS OsornioVargas, AR Roggli, VL Bonner, JC TI Lipopolysaccharide up-regulates platelet-derived growth factor (PDGF) alpha-receptor expression in rat lung myofibroblasts and enhances response to all PDCF isoforms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; ALVEOLAR MACROPHAGES; SIGNAL TRANSDUCTION; BINDING-PROTEIN; GENE-EXPRESSION; BETA-RECEPTOR; CDNA CLONING; ACINAR-CELLS; FIBROBLASTS; ACTIVATION AB Differential expression of PDGF receptor alpha and beta subunits controls the response of mesenchymal cells to the three PDGF isoforms (AA, AB, and BB). Cultured rat lung myofibroblasts (RLMF) possess abundant PDGF receptor-beta (PDGF-R beta) and little PDGF receptor-alpha (PDGF-R alpha). Here we show that LPS up-regulates expression of PDGF-R alpha and increases the sensitivity of RLMF to all three PDGF isoforms. Treatment of RLMF for 4 to 48 h with LPS enhanced PDGF-R alpha surface expression and mRNA 5- to 10-fold but caused no change in expression of PDGF-RP, Both RNA and protein synthesis were necessary for up-regulation of PDGF-R alpha, and the increase in PDGF-R alpha mRNA was most likely regulated at the transcriptional level, PDGF-R alpha up-regulation was not mediated by the IL-1R system and was independent of LPS-binding proteins in serum, Highly confluent cultures of RLMF responded more strongly to LPS than did subconfluent cultures. LPS treatment enhanced the mitogenic and chemotactic responses of RLMF to all PDGF isoforms at least threefold. We postulate that signal transduction by PDGF-receptor cup heterodimers was important in the enhanced responses to PDGF-AB and -BB. We propose that regulation of PDGF-R alpha is a critical event in the genesis of pulmonary fibroproliferative diseases. C1 NIEHS,LAB PULM PATHOBIOL D202,RES TRIANGLE PK,NC 27709. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,DEPT PATHOL,DURHAM,NC 27710. VET ADM MED CTR,DURHAM,NC 27710. NCI,DIV BASIC INVEST,MEXICO CITY,DF,MEXICO. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 50 TC 34 Z9 34 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1996 VL 156 IS 12 BP 4797 EP 4806 PG 10 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200037 PM 8648127 ER PT J AU Mawhorter, SD Stephany, DA Ottesen, EA Nutman, TB AF Mawhorter, SD Stephany, DA Ottesen, EA Nutman, TB TI Identification of surface molecules associated with physiologic activation of eosinophils - Application of whole-blood flow cytometry to eosinophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIPROLIFERATIVE ANTIBODY; LYMPHOCYTE-ACTIVATION; ADHESION MOLECULES; ENDOTHELIAL-CELLS; IN-VIVO; HLA-DR; EXPRESSION; ANTIGEN; RECEPTOR; ASTHMA AB Activation is central to the eosinophil's functional role as an immune responder cell. To evaluate such activation in cells freshly isolated from peripheral blood, a method for whole-blood immunostaining and flow cytometry-based eosinophil selection was developed. Simultaneous comparison of purified eosinophils and whole-blood cells revealed significant differences in the levels of expression of various surface molecules, which suggested that the purification process activated the eosinophils. Subsequent analyses were conducted with the whole-blood assay. When eosinophils from helminth-infected persons (n = 18) were compared with those from normal individuals (n = 10), the early activation marker CD69 was found to be significantly increased (geometric mean (GM) = 4.3 vs. 1.0%, p = 0.04). The granulocyte activation marker CD66 was also up-regulated on eosinophils from helminth patients (GM = 53.3 vs. 31.0%, p = 0.044), as was the tetraspan family molecule CD81 (TAPA-1; GM = 79.4 vs. 48.2%, p = 0.02). Conversely, in vivo CD23 (Fc(epsilon)RII) expression on eosinophils was decreased in the presence of parasitic infection (GM = 0.9 vs. 5.7%, p = 0.02). Expression of the eosinophil surface molecules CD69, CD81, and CD23 was significantly enhanced after cytokine stimulation in vitro with IL-3 or GM-CSF. In vivo, specific anthelmintic therapy resulted in decreased CD66 and CD25 expression (p < 0.05 compared with pretreatment) to levels approaching those seen in uninfected normal individuals. These findings indicate the dynamic nature of eosinophil surface molecules and demonstrate an important role for whole-blood staining in developing an understanding of the nature of eosinophil activation and of their role in inflammatory reactions to helminth parasites. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NIAID,MOLEC STRUCT LAB,NIH,BETHESDA,MD 20892. NR 52 TC 49 Z9 50 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 JUN 15 PY 1996 VL 156 IS 12 BP 4851 EP 4858 PG 8 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200044 PM 8648134 ER PT J AU Bowen, DC Sugiyama, J Ferns, M Hall, ZW AF Bowen, DC Sugiyama, J Ferns, M Hall, ZW TI Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE acetylcholine receptor; agrin; dystroglycan; muscle; receptor; synaptogenesis ID DYSTROPHIN-GLYCOPROTEIN COMPLEX; ACETYLCHOLINE-RECEPTOR; HEPARAN-SULFATE; LOCALIZATION; AGGREGATION; INHIBITION; MEMBRANE; CULTURE; NERVE; GENE AB During synaptogenesis, agrin, released by motor nerves, causes the clustering of acetylcholine receptors (AChRs) in the skeletal muscle membrane. Although muscle alpha-dystroglycan has been postulated to be the receptor for the activity of agrin, previous experiments have revealed a discrepancy between the biological activity of soluble fragments of two isoforms of agrin produced by nerves and muscles, respectively, and their ability to bind alpha-dystroglycan. We have determined the specificity of the signaling receptor by investigating whether muscle agrin can block the activity of neural agrin on intact C2 myotubes. We find that a large excess of muscle agrin failed to inhibit either the number of AChR clusters or the phosphorylation of the AChR induced by picomolar concentrations of neural agrin. These results indicate that neural, but not muscle, agrin interacts with the signaling receptor. Muscle agrin did block the binding of neural agrin to isolated alpha-dystroglycan, however, suggesting either that alpha-dystroglycan is not the signaling receptor or that its properties in the membrane are altered. Direct assay of the binding of muscle or neural agrin to intact myotubes revealed only low-affinity binding. We conclude that the signaling receptor for agrin is a high-affinity receptor that is highly specific for the neural form. C1 NINCDS,NIH,OFF DIRECTOR,BETHESDA,MD 20892. REGENERON PHARMACEUT INC,TARRYTOWN,NY 10591. MONTREAL GEN HOSP,RES INST,DEPT NEUROSURG,MONTREAL,PQ H3G 1A4,CANADA. NR 34 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1996 VL 16 IS 12 BP 3791 EP 3797 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UP383 UT WOS:A1996UP38300001 PM 8656273 ER PT J AU Blaxton, TA Zeffiro, TA Gabrieli, JDE Bookheimer, SY Carrillo, MC Theodore, WH Disterhoft, JF AF Blaxton, TA Zeffiro, TA Gabrieli, JDE Bookheimer, SY Carrillo, MC Theodore, WH Disterhoft, JF TI Functional mapping of human learning: A positron emission tomography activation study of eyeblink conditioning SO JOURNAL OF NEUROSCIENCE LA English DT Article DE learning; eyeblink conditioning; positron emission tomography (PET); cerebellum; hippocampus; frontal cortex; basal ganglia ID NICTITATING-MEMBRANE RESPONSE; CEREBELLAR NUCLEI; EYE-BLINK; RABBIT; LESIONS; MEMORY; CORTEX; DISCRIMINATION; ACQUISITION; TRACE AB Regional cerebral blood flow (rCBF) was measured using positron emission tomography during eyeblink conditioning in young adults. Subjects were scanned in three experimental conditions: delay conditioning, in which binaural tones preceded air puffs to the right eye by 400 msec; pseudoconditioning, in which presentations of tone and air puff stimuli were not correlated in time; and fixation rest, which served as a baseline control. Compared with fixation, pseudoconditioning produced rCBF increases in frontal and temporal cortex, basal ganglia, left hippocampal formation, and pens. Learning-specific activations were observed in conditioning as compared with pseudoconditioning in bilateral frontal cortex, left thalamus, right medial hippocampal formation, left lingual gyrus, pens, and bilateral cerebellum; decreases in rCBF were observed for bilateral temporal cortex, and in the right hemisphere in putamen, cerebellum, and the lateral aspect of hippocampal formation. Blood flow increased as the level of learning increased in the left hemisphere in caudate, hippocampal formation, fusiform gyrus, and cerebellum, and in right temporal cortex and pens. In contrast, activation in left frontal cortex decreased as learning increased. These functional imaging results implicate many of the same structures identified by previous lesion and recording studies of eyeblink conditioning in animals and humans and suggest that the same brain regions in animals and humans mediate multiple forms of associative learning that give meaning to a previously neutral stimulus. C1 NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. STANFORD UNIV,DEPT PSYCHOL,STANFORD,CA 94305. NORTHWESTERN UNIV,DEPT MOLEC & CELL BIOL,CHICAGO,IL 60611. OI Disterhoft, John/0000-0002-8817-7913 FU NIA NIH HHS [R0IAG06796]; NIDA NIH HHS [R0IDA07633]; NIMH NIH HHS [R0IMH47340] NR 67 TC 130 Z9 131 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1996 VL 16 IS 12 BP 4032 EP 4040 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UP383 UT WOS:A1996UP38300024 PM 8656296 ER PT J AU Shipston, MJ Armstrong, DL AF Shipston, MJ Armstrong, DL TI Activation of protein kinase C inhibits calcium-activated potassium channels in rat pituitary tumour cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; CA-2+-ACTIVATED K+ CHANNELS; PROLACTIN SECRETION; CYTOSOLIC CA-2+; GH3 CELLS; MODULATION; LINE; SOMATOSTATIN; RECORDINGS; CURRENTS AB 1. The regulation of large-conductance, calcium- and voltage-dependent potassium (BK) channels by protein kinase C (PKC) was investigated in clonal rat anterior pituitary cells (GH(4)C(1)), which were voltage clamped at -40 mV in a physiological potassium gradient through amphotericin-perforated patches. 2. Maximal activation of PKC by 100 nM phorbol 12,13-dibutyrate (PdBu) almost completely inhibited the voltage-activated outward current through BK channels. In contrast PdBu had no significant effect on the residual outward current after block of BK channels with 2 mM TEA or 30 nM charybdotoxin. In sing le-channel recordings from cell-attached patches, PdBu reduced the open probability of BK channels more than eightfold with no significant effect on mean open lifetime or unitary conductance. 3. The effects of PdBu on BK channels were not mimicked by the 4 alpha-isomer, which does not activate PKC, and were blocked almost completely by 25 mu M chelerythrine, a specific, non-competitive PKC inhibitor. 4. PdBu had no significant effect on the amplitude of the pharmacologically isolated, high voltage-activated calcium current. 5. Inhibition of BK channel activity by PKC provides the first molecular mechanism linking hormonal activation of phospholipase C to sustained excitability in pituitary cells. C1 UNIV EDINBURGH,DEPT PHARMACOL,EDINBURGH EH8 7NA,MIDLOTHIAN,SCOTLAND. RP Shipston, MJ (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. RI Shipston, Mike/C-7309-2013 OI Shipston, Mike/0000-0001-7544-582X FU Wellcome Trust NR 34 TC 60 Z9 60 U1 0 U2 0 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 JUN 15 PY 1996 VL 493 IS 3 BP 665 EP 672 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UV411 UT WOS:A1996UV41100006 PM 8799890 ER PT J AU Egan, KM Newcomb, PA Longnecker, MP TrenthamDietz, A Baron, JA Trichopoulos, D Stampfer, MJ Willett, WC AF Egan, KM Newcomb, PA Longnecker, MP TrenthamDietz, A Baron, JA Trichopoulos, D Stampfer, MJ Willett, WC TI Jewish religion and risk of breast cancer SO LANCET LA English DT Article AB Background The excess risk of breast cancer among Jewish women has been attributed to the effects of difference in lifestyle and reproductive patterns, but there is now evidence that Jewish women may be more likely than other women to inherit mutations in breast-cancer genes. We investigated whether any excessive risk among Jewish women is confined to those with a family history of breast cancer. Methods We assessed the effect of Jewish religion on breast cancer in a large population-based case-control study (6611 women with breast cancer and 9026 controls) in USA. Participants were given telephone interviews and asked about known and suspected risk factors for breast cancer. Findings Overall, Jewish women had only a slightly raised relative risk of breast cancer (1 . 10 [95% CI 0 . 84-1 . 44]; p=0 . 49). However, the relative risk was much higher for Jewish women with a first-degree relative who had breast cancer (3 . 78 [1 . 74-8 . 16]; p<0 . 001). The effect of family history was greater in Jewish women than in women of other religions (p interaction=0 . 05). Interpretation These results are consistent with data suggesting that certain groups of Jewish women have a higher than expected rate of mutation in the breast-cancer gene BRCA1. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. DARTMOUTH COLL SCH MED,DEPT MED,HANOVER,NH. DARTMOUTH COLL SCH MED,DEPT FAMILY & COMMUNITY MED,HANOVER,NH. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. RP Egan, KM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA 47305, CA 47147] NR 8 TC 46 Z9 46 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 JUN 15 PY 1996 VL 347 IS 9016 BP 1645 EP 1646 DI 10.1016/S0140-6736(96)91485-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UQ701 UT WOS:A1996UQ70100008 PM 8642956 ER PT J AU Biggar, RJ Miotti, PG Taha, TE Mtimavalye, L Broadhead, R Justesen, A Yellin, F Liomba, G Miley, W Waters, D Chiphangwi, D Goedert, JJ AF Biggar, RJ Miotti, PG Taha, TE Mtimavalye, L Broadhead, R Justesen, A Yellin, F Liomba, G Miley, W Waters, D Chiphangwi, D Goedert, JJ TI Perinatal intervention trial in Africa: Effect of a birth canal cleansing intervention to prevent HIV transmission SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; HIGH-RISK; INFECTION; CHLORHEXIDINE; CHILDREN; INUTERO; INFANTS; MOTHERS; KIGALI AB Background Perinatal transmission of human immunodeficiency virus (HIV) type 1 contributes significantly to infant mortality. Exposure in the birth canal may account for some transmission. We examined the efficacy of a birth canal washing procedure in reducing perinatal transmission in Malawi. Methods The infection status of infants of 3327 control women (conventional delivery procedures) was compared with that of 3637 infants of intervention-delivered women. The infants' HIV status was determined by polymerase chain reaction on dried blood spots collected at 6 and 12 weeks of age. The intervention consisted of manual cleansing of the birth canal with a cotton pad soaked in 0 . 25% chlorhexidine, which was done on admission in labour and every 4 h until delivery. Findings No adverse reactions to the intervention procedure were seen. 2094 (30%) of the enrolled women were HIV-infected, and 59% of their infants were seen in follow-up. Among 982 vaginal vertex singleton deliveries to HIV-infected women, 269 (27%) infants were infected. The intervention had no significant impact on HIV transmission rates (27% in 505 intervention women compared With 28% in 477 control women), except when membranes were ruptured more than 4 h before delivery (transmission 25% in the intervention group vs 39% in the control group). Interpretation If birth canal exposure is an important risk factor, different or additional methods to reduce the risk of perinatal HIV transmission should be tested. Alternatively, perhaps birth canal exposure is not a major contributor to perinatal infection risk. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,MINIST HLTH,RES PROJECT,BLANTYRE,MALAWI. QUEEN ELIZABETH CENT HOSP,DEPT OBSTET & GYNAECOL,BLANTYRE,MALAWI. QUEEN ELIZABETH CENT HOSP,DEPT PEDIAT,BLANTYRE,MALAWI. COMP SCI CORP,ROCKVILLE,MD. QUEEN ELIZABETH CENT HOSP,DEPT PATHOL,BLANTYRE,MALAWI. FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD. FU NCI NIH HHS [N01-CP-33005]; NIAID NIH HHS [N01-AI-35173-117] NR 29 TC 162 Z9 165 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 15 PY 1996 VL 347 IS 9016 BP 1647 EP 1650 DI 10.1016/S0140-6736(96)91486-5 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA UQ701 UT WOS:A1996UQ70100009 PM 8642957 ER PT J AU Koonin, EV AF Koonin, EV TI Pseudouridine synthases: Four families of enzymes containing a putative uridine-binding motif also conserved in dUTPases and dCTP deaminases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACID SUBSTITUTION MATRICES; ESCHERICHIA-COLI; TRANSFER-RNA; SACCHAROMYCES-CEREVISIAE; RIBOSOMAL-RNA; GENE; MUTATIONS AB Using a combination of several methods for protein sequence comparison and motif analysis, it is shown that the four recently described pseudouridine synthases with different specificities belong to four distinct families. Three of these families share two conserved motifs that are likely to be directly involved in catalysis, One of these motifs is detected also in two other families of enzymes that specifically bind uridine, namely deoxycitidine triphosphate deaminases and deoxyuridine triphosphatases, It is proposed that this motif is an essential part of the uridine-binding site, Two of the pseudouridine synthases, one of which modifies the anticodon arm of tRNAs and the other is predicted to modify a portion of the large ribosomal subunit RNA belonging to the peptidyltransferase center, are encoded in all extensively sequenced genomes, including the 'minimal' genome of Mycoplasma genitalium, These particular RNA modifications and the respective enzymes are likely to be essential for the functioning of any cell. RP Koonin, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. NR 48 TC 178 Z9 182 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1996 VL 24 IS 12 BP 2411 EP 2415 DI 10.1093/nar/24.12.2411 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW123 UT WOS:A1996UW12300029 PM 8710514 ER PT J AU Hagiwara, K Harris, CC AF Hagiwara, K Harris, CC TI 'Long distance sequencer' method; A novel strategy for large DNA sequencing projects SO NUCLEIC ACIDS RESEARCH LA English DT Article C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 6 TC 31 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1996 VL 24 IS 12 BP 2460 EP 2461 DI 10.1093/nar/24.12.2460 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW123 UT WOS:A1996UW12300040 PM 8710525 ER PT J AU Gail, MH Mark, SD Carroll, RJ Green, SB Pee, D AF Gail, MH Mark, SD Carroll, RJ Green, SB Pee, D TI On design considerations and randomization-based inference for community intervention trials SO STATISTICS IN MEDICINE LA English DT Article ID SAMPLE-SIZE REQUIREMENTS; CLUSTER RANDOMIZATION; DISEASE PREVENTION; ISSUES; REGRESSION; VARIANCE; POWER; TESTS AB This paper discusses design considerations and the role of randomization-based inference in randomized community intervention trials. We stress that longitudinal follow-up of cohorts within communities often yields useful information on the effects of intervention on individuals, whereas cross-sectional surveys can usefully assess the impact of intervention on group indices of health. We also discuss briefly special design considerations, such as sampling cohorts from targeted subpopulations (for example, heavy smokers), matching the communities, calculating sample size, and other practical issues. We present randomization tests for matched and unmatched cohort designs. As is well known, these tests necessarily have proper size under the strong null hypothesis that treatment has no effect on any community response. It is less well known, however, that the size of randomization tests can exceed nominal levels under the 'weak' null hypothesis that intervention does not affect the average community response. Because this weak null hypothesis is of interest in community intervention trials, we study the size of randomization tests by simulation under conditions in which the weak null hypothesis holds but the strong null hypothesis does not. In unmatched studies, size may exceed nominal levels under the weak null. hypothesis if there are more intervention than control communities and if the variance among community responses is larger among control communities than among intervention communities; size may also exceed nominal levels if there are more control than intervention communities and if the variance among community responses is larger among intervention communities. Otherwise, size is likely near nominal levels. To avoid such problems, we recommend use of the same numbers of control and intervention communities in unmatched designs. Pair-matched designs usually have size near nominal levels, even under the weak null hypothesis. We have identified some extreme cases, unlikely to arise in practice, in which even the size of pair-matched studies can exceed nominal levels. These simulations, however, tend to confirm the robustness of randomization tests for matched and unmatched community intervention trials, particularly if the latter designs have equal numbers of intervention and control communities. We also describe adaptations of randomization tests to allow for covariate adjustment, missing data, and application to cross-sectional surveys. We show that covariate adjustment can increase power, but such power gains diminish as the random component of variation among communities increases, which corresponds to increasing intraclass correlation of responses within communities. We briefly relate our results to model-based methods of inference for community intervention trials that include hierarchical models such as an analysis of variance model with random community effects and fixed intervention effects. Although we have tailored this paper to the design of community intervention trials, many of the ideas apply to other experiments in which one allocates groups or clusters of subjects at random to intervention or control treatments. C1 TEXAS A&M UNIV,DEPT STAT,COLLEGE STN,TX 77843. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD 20852. RP Gail, MH (reprint author), NCI,DIV CANC ETIOL,EXECUT PLAZA N,ROOM 431,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-57030] NR 57 TC 124 Z9 126 U1 1 U2 17 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1996 VL 15 IS 11 BP 1069 EP 1092 DI 10.1002/(SICI)1097-0258(19960615)15:11<1069::AID-SIM220>3.0.CO;2-Q PG 24 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UR768 UT WOS:A1996UR76800001 PM 8804140 ER PT J AU Blair, RC Troendle, JF Beck, RW AF Blair, RC Troendle, JF Beck, RW TI Control of familywise errors in multiple endpoint assessments via stepwise permutation tests SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS; OPTIC NEURITIS AB We describe permutation based sequentially rejective multiple comparison procedures useful in multiple endpoint assessments. We used Monte Carlo methods to compare the power of these newly devised tests to that of tests due to Helm and Rom as well as to the classical Bonferroni method. We illustrate applications of the methods with analysis of visual field data collected from optic neuritis patients. We conclude that the new methods are particularly useful when there are many endpoints involved, the data are significantly correlated, and/or the distributional assumptions are questionable. C1 UNIV S FLORIDA,COLL PUBL HLTH,DEPT COMMUNITY & FAMILY HLTH,TAMPA,FL 33612. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. JAEB CTR HLTH RES,TAMPA,FL 33613. RP Blair, RC (reprint author), UNIV S FLORIDA,COLL PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,13201 BRUCE B DOWNS BLVD,MDC BOX 56,TAMPA,FL 33612, USA. NR 17 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1996 VL 15 IS 11 BP 1107 EP 1121 DI 10.1002/(SICI)1097-0258(19960615)15:11<1107::AID-SIM222>3.0.CO;2-T PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UR768 UT WOS:A1996UR76800003 PM 8804142 ER PT J AU Deryshire, MK Weinstock, KG Strathern, JN AF Deryshire, MK Weinstock, KG Strathern, JN TI HST1, a new member of the SIR2 family of genes SO YEAST LA English DT Article DE silencing; mating type ID SILENT MATING LOCI; SACCHAROMYCES-CEREVISIAE; SHUTTLE VECTORS; YEAST; DNA; RNA; EXPRESSION; CLONING; ELEMENT; REGION AB A novel Saccharomyces cerevisiae gene, HST1, was identified from among anonymous cDNAs and the complete corresponding genomic clone was isolated and sequenced. HST1 is very closely related to SIR2, showing 71% sequence identity over 84% of its length. Polymerase chain reaction with degenerate primers on S. cerevisiae DNA identified three additional SIR2-related genes designated HST2, HST3 and HST4. The sequences of HST2, HST3 and HST4 correspond to sequences previously released by the S. cerevisiae genome sequencing project as U33335, NCBI gi:965078; X87331, NCBI gi:829135; and Z48784, YD9346.03, respectively. Disruption of HST1 has shown no phenotype with respect to mechanisms in which SIR2 has a role, namely, regional silencing of HML alpha, or in rDNA recombination. The sequence of HST1 has been deposited in the DDBJ, EMBL and GenBank at NCBI database under Accession Number L47120. C1 NCI, GENE REGULAT & CHROMOSOME BIOL LAB, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. INST GENOM RES, ROCKVILLE, MD 20850 USA. NR 28 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD JUN 15 PY 1996 VL 12 IS 7 BP 631 EP 640 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA UU860 UT WOS:A1996UU86000002 ER PT J AU SzentGyorgyi, C AF SzentGyorgyi, C TI A simplified method for the repeated replacement of yeast chromosomal sequences with in vitro mutations SO YEAST LA English DT Article DE CYH2(S); counterselection; PCR ID SACCHAROMYCES-CEREVISIAE; GENE; DNA; TRANSFORMATION; SELECTION; STRAINS AB A strategy for gene replacement in Saccharomyces cerevisiae has been modified to facilitate the repeated substitution of a chromosomal locus with in vitro generated variant sequences, so that the resulting locus contains only the desired mutation and is free of extraneous vector DNA. The construction of an internally deleted chromosomal target locus carrying the counterselectable CYH2(S) marker and a second positively selectable marker has been simplified; the design of the locus has been altered to increase the frequency of authentic gene replacements obtained upon the subsequent integration of in vitro mutated DNA. The modified chromosomal target locus is amenable to replacement using either of two transformation protocols: (i) integration of a second positively selectable plasmid carrying mutant sequences to form a tandem intermediate structure at the locus; upon counterselection on cycloheximide, all vector sequence is excised to give the desired replacement at high frequency (>70%); (ii) single-step integration of a linear segment of mutated genomic DNA by selection for cycloheximide resistance. A subsequent screen for the loss of the positively selectable target locus marker detects the desired replacement at modest frequency (>2%). Polymerase chain reaction using multiple primers in a single amplification reaction is useful for monitoring these variously modified chromosomal loci. RP NIDDKD, CELLULAR & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD JUN 15 PY 1996 VL 12 IS 7 BP 667 EP 672 DI 10.1002/(SICI)1097-0061(19960615)12:7<667::AID-YEA955>3.0.CO;2-A PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA UU860 UT WOS:A1996UU86000005 PM 8810040 ER PT J AU Hahn, H Wicking, C Zaphiropoulos, PG Gailani, MR Shanley, S Chidambaram, A Vorechovsky, I Holmberg, E Unden, AB Gillies, S Negus, K Smyth, I Pressman, C Leffell, DJ Gerrard, B Goldstein, AM Dean, M Toftgard, R ChenevixTrench, G Wainwright, B Bale, AE AF Hahn, H Wicking, C Zaphiropoulos, PG Gailani, MR Shanley, S Chidambaram, A Vorechovsky, I Holmberg, E Unden, AB Gillies, S Negus, K Smyth, I Pressman, C Leffell, DJ Gerrard, B Goldstein, AM Dean, M Toftgard, R ChenevixTrench, G Wainwright, B Bale, AE TI Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome SO CELL LA English DT Article ID TUMOR SUPPRESSOR GENE; GORLIN SYNDROME; COLORECTAL TUMORIGENESIS; POINT MUTATIONS; SEGMENT; PROTEIN; RETINOBLASTOMA; POLARITY; POLYMORPHISMS; ASSOCIATION AB The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety of other tumors, and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial and sporadic BCCs display loss of heterozygosity in this region, consistent with the gene being a tumor suppressor. A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, patched, was isolated from a YAC and cosmid contig of the NBCCS region. Mutation analysis revealed alterations of PTC in NBCCS patients and in related tumors. We propose that a reduction in expression of the patched gene can lead to the developmental abnormalities observed in the syndrome and that complete loss of patched function contributes to transformation of certain cell types. C1 NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20852. KAROLINSKA INST,NOVUM,DEPT BIOSCI,CTR NUTR & TOXICOL,S-14157 HUDDINGE,SWEDEN. KAROLINSKA HOSP,DEPT DERMATOL,S-17176 STOCKHOLM,SWEDEN. ROYAL BRISBANE HOSP,QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06250. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06250. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06250. RP Hahn, H (reprint author), UNIV QUEENSLAND,CTR CELLULAR & MOLEC BIOL,ST LUCIA,QLD 4072,AUSTRALIA. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Wicking, Carol/0000-0002-7225-3803 FU NCI NIH HHS [K11CA60199, P30CA16359, R01CA57605] NR 64 TC 1267 Z9 1297 U1 5 U2 32 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 14 PY 1996 VL 85 IS 6 BP 841 EP 851 DI 10.1016/S0092-8674(00)81268-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UR604 UT WOS:A1996UR60400008 PM 8681379 ER PT J AU Xie, WW Kaetzel, MA Bruzik, KS Dedman, JR Shears, SB Nelson, DJ AF Xie, WW Kaetzel, MA Bruzik, KS Dedman, JR Shears, SB Nelson, DJ TI Inositol 3,4,5,6-tetrakisphosphate inhibits the calmodulin-dependent protein kinase II-activated chloride conductance in T84 colonic epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYSTIC-FIBROSIS; AIRWAY EPITHELIA; BINDING PROTEIN; ACINAR-CELLS; LINE T84; CALCIUM; CHANNELS; STIMULATION; PHOSPHATES; SECRETION AB The mechanism by which inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P-4) regulates chloride (Cl-) secretion was evaluated in the colonic epithelial cell line T84 using whole cell voltage clamp techniques. Our studies focused on the calcium-dependent chloride conductance (gCl(Ca)) that was activated either by mobilizing intracellular calcium (Ca-i) stores with thapsigargin or by introduction of the autonomous, autophosphorylated calmodulin-dependent protein kinase II (CaMKII) into the cell via the patch pipette. Basal concentrations of Ins(3,4,5,6)P-4 (1 mu M) present in the pipette solution had no significant effect on Cl- current; however, as the concentration of the polyphosphate was increased there was a corresponding reduction in anion current, with near complete inhibition at 8-10 mu M Ins(3,4,5,6)P-4. Corresponding levels are found in cells after sustained receptor-dependent activation of phospholipase C. The Ins(3,4,5,6)P-4-induced inhibition of gCl(Ca) was isomer specific; neither Ins(1,3,4,5)P-4, Ins(1,3,4,6)P-4, Ins(1,4,5,6)P-4, nor Ins(1,3,4,5,6)P-5 induced current inhibition at concentrations of up to 100 mu M. Annexin TV also plays an inhibitory role in modulating gCl(Ca) in T84 cells. When 2 mu M annexin IV was present in the pipette solution, a concentration that by itself has no effect on gCl(Ca), the potency of Ins(3,4,5,6)P-4 was approximately doubled. The combination of Ins(3,4,5,6)P-4 and annexin TV did not alter the in vitro activity of CaMKII. These data demonstrate that Ins(3,4,5,6)P-4 is an additional cellular signal that participates in the control of salt and fluid secretion, pH balance, osmoregulation, and other physiological activities that depend upon gCl(Ca) activation. Ins(3,4,5,6)P-4 metabolism and action should also be taken into account when designing treatment strategies for cystic fibrosis. C1 UNIV CHICAGO,DEPT NEUROL,CHICAGO,IL 60637. UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,CHICAGO,IL 60612. UNIV CINCINNATI,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,CINCINNATI,OH 45267. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. FU NIDDK NIH HHS [R01 DK46433]; NIGMS NIH HHS [R01 GM36823]; PHS HHS [R01 41470] NR 36 TC 101 Z9 101 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 JUN 14 PY 1996 VL 271 IS 24 BP 14092 EP 14097 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000026 PM 8662902 ER PT J AU Shatwell, KP Dancis, A Cross, AR Klausner, RD Segal, AW AF Shatwell, KP Dancis, A Cross, AR Klausner, RD Segal, AW TI The FRE1 ferric reductase of Saccharomyces cerevisiae is a cytochrome b similar to that of NADPH oxidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IRON UPTAKE; FLAVOCYTOCHROME; PURIFICATION; NEUTROPHILS; PROTEIN AB Plasma membrane preparations from strains of the yeast Saccharomyces cerevisiae gave a reduced minus oxidized spectrum characteristic of a b-type cytochrome and very similar to the spectrum of flavocytochrome b(558) of human neutrophils. The magnitude of the signal correlated with the level of ferric reductase activity and the copy number of the FRE1 gene, indicating that the FRE1 protein is a cytochrome b. Sequence similarities with the flavin binding site of flavocytochrome b(558) and other members of the ferredoxin-NADP reductase family, together with increased levels of noncovalently bound FAD and iodonitrotetrazolium violet reductase activity in membranes from a yeast strain overexpressing ferric reductase, suggested that the FRE1 protein may also carry a flavin group. Potentiometric titrations indicated that FRE1, like neutrophil NADPH oxidase, has an unusually low redox potential, in the region of -250 mV, and binds CO. C1 NICHHD, NIH, BETHESDA, MD 20892 USA. SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. RP UCL, DEPT MED, 5 LONDON ST, LONDON WC1E 6JJ, ENGLAND. OI Segal, Anthony/0000-0001-7602-9043 FU NIAID NIH HHS [AI24838]; Wellcome Trust NR 21 TC 105 Z9 108 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 JUN 14 PY 1996 VL 271 IS 24 BP 14240 EP 14244 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000047 PM 8662973 ER PT J AU Fawcett, TW Eastman, HB Martindale, JL Holbrook, NJ AF Fawcett, TW Eastman, HB Martindale, JL Holbrook, NJ TI Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-PROTEIN; GROWTH ARREST; C/EBP; GENE; TRANSCRIPTION; EXPRESSION; ISOFORMS; CELLS; LAP AB GADD153, a ubiquitously expressed member of the CCAAT/enhancer-binding protein (C/EBP) family is induced by a wide variety of growth-arresting and DNA-damaging agents. Functionally, GADD153 has been postulated to act as a dominant-negative regulator of C/EBPs. Therefore we sought to gain evidence for interactions between GADD153 and other C/EBPs during cellular responses to stress. In this report we have demonstrated that treatment of rat pheochromocytoma PC12 cells with sodium arsenite leads to enhanced expression of C/ERP-beta and GADD153 (growth arrest and DNA damage inducible gene 153) but not other C/EBPs. Coimmunoprecipitation experiments provided evidence for the formation of endogenous GADD153-C/EBP-beta complexes in arsenite-treated cells. Additional experiments were performed to determine the role of such complexes in regulating GADD153 expression. Previous studies in our laboratory demonstrated that the GADD153 promoter contains a C/EBP binding site through which other C/EBPs interact to transactivate GADD153 expression in liver hepatoma cells. Here, we demonstrate that extracts prepared from arsenite-treated PC12 cells likewise show increased amounts of factors capable of binding to the GADD153-C/EBP site and that these complexes are comprised at least in part of C/EBP-beta. Forced expression of C/EBP-beta was found to be capable of transactivating the GADD153 promoter in PC12 cells cotransfected with plasmids expressing a GADD153 reporter gene and C/EBP-beta protein. However, overexpression of GADD153 inhibited the transactivation of the GADD153 promoter by C/EBP-beta. These findings provide evidence for an autoregulatory loop in which stress-induced GADD153 feeds back to attenuate GADD153 expression during the cellular response to stress. C1 NIA,GENE EXPRESS & AGING SECT,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 24 TC 96 Z9 97 U1 1 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 JUN 14 PY 1996 VL 271 IS 24 BP 14285 EP 14289 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000054 PM 8662954 ER PT J AU Kole, HK Garant, MJ Kole, S Bernier, M AF Kole, HK Garant, MJ Kole, S Bernier, M TI A peptide-based protein-tyrosine phosphatase inhibitor specifically enhances insulin receptor function in intact cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; PHOSPHOTYROSINE PHOSPHATASE; FATTY-ACIDS; PHOSPHATIDYLINOSITOL 3-KINASE; MULTISITE PHOSPHORYLATION; CATALYTIC FRAGMENT; SKELETAL-MUSCLE; RAT ADIPOCYTES; KINASE; ACTIVATION AB 3S-peptide-I is a synthetic tris-sulfotyrosyl dodecapeptide corresponding to the major site of insulin receptor autophosphorylation that potently inhibits dephosphorylation of the insulin receptor in a cell-free system and in digitonin-permeabilized Chinese hamster ovary (CHO) cells overexpressing the human insulin receptors (CHO/HIRc cells) (Liotta, A. S., Kole, H. K., Fales, H. M., Roth, J., and Bernier, M. (1994) J. Biol. Chem. 269, 22996-23001), In the present study, we found that 3S-peptide-I was not capable of inhibiting dephosphorylation of the epidermal growth factor (EGF) receptors in digitonin-permeabilized CHO cells that overexpress human EGF receptors (CHO/EGF-R cells), Moreover, the addition of a N-stearyl derivative of 3S-peptide-I to intact CHO/HIRc cells caused a concentration-dependent increase in insulin-stimulated phosphorylation of the insulin receptor, with a maximum effect (similar to 2.7-fold) at 50 mu M. In contrast, ligand-stimulated EGF receptor phosphorylation in CHO/EGF-R cells was not affected by the presence of stearyl 3S-peptide-I, Furthermore, treatment of CHO/HIRc cells with this N-stearyl peptide led to a significant enhancement of the insulin induced association of phosphatidylinositol (PI) 3-kinase activity with insulin receptor substrate 1 and the activation of mitogen-activated protein kinase, However, stearyl 3S-peptide-I had no effect on the EGF stimulated activation of PI-3-kinase and mitogen-activated protein kinase in CHO/EGF-R cells, These data indicate that this tris-sulfotyrosyl dodecapeptide selectively enhances insulin signal transduction by specifically inhibiting dephosphorylation of the insulin receptor in intact cells. RP Kole, HK (reprint author), NIA,DIABET SECT,LAB CLIN PHYSIOL,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Bernier, Michel/0000-0002-5948-368X NR 63 TC 33 Z9 34 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 14 PY 1996 VL 271 IS 24 BP 14302 EP 14307 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000057 PM 8662948 ER PT J AU TsaiMorris, CH Buczko, E Geng, Y GamboaPinto, A Dufau, ML AF TsaiMorris, CH Buczko, E Geng, Y GamboaPinto, A Dufau, ML TI The genomic structure of the rat corticotropin releasing factor receptor - A member of the Class II G protein-coupled receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXPRESSION CLONING; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; LEYDIG-CELLS; HORMONE; GENE; PEPTIDE; CDNA; VARIANTS; BINDING AB Isolation and structural characterization of the rat corticotropin releasing factor receptor (CRFR) gene was performed to determine the exon/intron organization of the coding region and the potential for splice variants, The CRFR gene contains 13 exons and 12 introns, and the positions of the exon/intron junctions are similar to those of other Class II G protein-coupled receptor genes including the parathyroid hormone and glucagon receptors, The promoter resides within 593 base pairs of the initiation codon and the major transcriptional start site at nucleotide -238. This domain does not possess a TATA box but contains multiple Spl and AP-2 sites upstream and downstream of the major transcriptional start site, Intron junctions were identified in the extracellular, transmembrane (TM), and cytoplasmic (C) domains of the CRFR, giving the potential for differential signal transduction by splice variants, CRFR cDNAs derived from rat Leydig cell mRNA included the pituitary Form A, which spans exons 1-13, and two splice variants with deletion of exon 3 or exons 7, 11, and 12, An evolutionary link between the intronless TM/C module of the glycoprotein hormone receptors and the intron-containing TM/C module of the CRFR is suggested by the common position of the luteinizing hormone receptor Form D alternate acceptor splice site and the CRFR intron 12. C1 NICHHD,SECT MOL ENDOCRINOL,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NR 28 TC 49 Z9 51 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 14 PY 1996 VL 271 IS 24 BP 14519 EP 14525 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000086 PM 8662941 ER PT J AU Heisler, LM Feng, GH Jin, DJ Gross, CA Landick, R AF Heisler, LM Feng, GH Jin, DJ Gross, CA Landick, R TI Amino acid substitutions in the two largest subunits of Escherichia coli RNA polymerase that suppress a defective rho termination factor affect different parts of the transcription complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-SUBUNIT; RIFAMPICIN-RESISTANT; 3-DIMENSIONAL STRUCTURE; FUNCTIONAL TOPOGRAPHY; REPLICATION CONTROL; CONSERVED REGIONS; TERNARY COMPLEXES; CRYSTAL-STRUCTURE; CHAIN INITIATION; KLENOW FRAGMENT AB Among the earliest rpoBC mutations identified are three suppressors of the conditional lethal rho allele, rho201. These three mutations are of particular interest because, unlike rpoB8, they do not increase termination at all rho-dependent and p-independent terminators. rpoB211 and rpoB212 both change Asn-1072 to His in conserved region H of rpoB (beta N1072H), whereas rpoC214 changes Arg-352 to Cys in conserved region C of rpoC (beta'R352C). Both substitutions significantly reduce the overall rate of transcript elongation in vitro relative to wild-type RNA polymerase; however, they probably slow elongation for different reasons. The nucleotide triphosphate concentrations required at the T7 A1 promoter for both abortive trinucleotide synthesis and for promoter escape are much greater for beta N1072H. In contrast, beta'R352C and two adjacent substitutions (beta'G351S and beta'S350F), but not beta N1072H, formed open complexes of greatly reduced stability. The sequence in this region of beta' modestly resembles a region of Escherichia coli DNA polymerase I that contacts the phosphate backbone of DNA in co crystals. Core determinants affecting open complex formation do not reside exclusively in beta', however, since the Rif(r) mutation rpoB2 in beta also dramatically destabilized open complexes. We suggest that the principal defects of the two Rho-suppressing substitutions may differ, perhaps reflecting a greater role of beta region H in nucleoside triphosphate binding and nucleotide addition and of beta' region C in contacts to the DNA strands that could be important for translocation. Although both probably suppress rho201 by slowing RNA chain elongation, these differences may lead to terminator specificity that depends on the rate-limiting step at different sites. C1 UNIV WISCONSIN, DEPT BACTERIOL, MADISON, WI 53706 USA. WASHINGTON UNIV, DEPT BIOL, ST LOUIS, MO 63130 USA. NCI, MOLEC BIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI 19635]; NIGMS NIH HHS [GM 38660] NR 99 TC 14 Z9 14 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 14 PY 1996 VL 271 IS 24 BP 14572 EP 14583 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000094 PM 8662850 ER PT J AU Lobocka, M Yarmolinsky, M AF Lobocka, M Yarmolinsky, M TI P1 plasmid partition: A mutational analysis of ParB SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE partition; bacteriophage P1; OmpT; BNPS-skatole; ribosomal frameshifting ID INTEGRATION HOST FACTOR; CIS-ACTING REGION; ESCHERICHIA-COLI; F-PLASMID; NUCLEOTIDE-SEQUENCE; BACTERIAL PLASMIDS; STABILITY OPERON; CELL-CYCLE; PROTEIN; GENE AB P1 plasmid partition to daughter cells requires plasmid proteins, ParA and ParB, and a centromere analog, parS, to which ParB binds. ParA and ParB decrease the loss frequencies of some low copy number plasmid vectors with parS inserts, as well as that of P1 itself, more than 100-fold. Unexpectedly, we find that Par proteins can actively destabilize other parS-plasmid constructs under similar conditions. Only ParB is required for this partition dysfunction. The destabilization can be dramatic; certain parS-plasmid constructs cannot even be maintained in the presence of ParB. We take advantage of this partition dysfunction to select parB mutants unable to destabilize a particularly ParB-sensitive parS-plasmid. The mutations obtained are widely distributed in the gene. Several of the mutations affected binding of ParB to parS; others did not. Amino acid substitutions that affected binding without influencing dimerization were mapped to two separate regions of ParB. C-Terminal amino acid substitutions in ParB blocked its dimerization and binding to parS, as did deletions of the entire C-terminal part of the protein. These results are consistent with ParB binding to parS as a dimer and suggest that the C-terminal part is a dimerization domain of the protein. Cell extracts of a frameshift mutant analyzed contained, in addition to the expected truncated ParB, a second species of ParB with the normal C-terminal part. Apparently, a site of ribosomal frameshifting is encoded within parB, at which some ribosomes change reading frame in the mutant. All obtained mutant ParB proteins were unable to complement the partition defect of a parB null mutant mini-P1. This suggests that the initial reactions between ParB and parS leading to partition dysfunction and to partition function are similar. (C) 1996 Academic Press Limited RP Lobocka, M (reprint author), NCI,NIH,BIOCHEM LAB,BLDG 37,ROOM 4D-15,BETHESDA,MD 20892, USA. NR 66 TC 63 Z9 63 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 14 PY 1996 VL 259 IS 3 BP 366 EP 382 DI 10.1006/jmbi.1996.0326 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP667 UT WOS:A1996UP66700006 PM 8676375 ER PT J AU Park, CS Park, R Krishna, G AF Park, CS Park, R Krishna, G TI Constitutive expression and structural diversity of inducible isoform of nitric oxide synthase in human tissues SO LIFE SCIENCES LA English DT Article DE human; inducible NO synthase; northern blot; constitutive expression; structural diversity ID MOLECULAR-CLONING; CELL-LINE; PURIFICATION; ENZYME AB Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) plays a major role in immune responses to bacteria and tumors, and the gene is induced by endotoxin and cytokines. However, we have detected iNOS cDNA sequences expressed constitutively at low level from human retinal, cerebellar and skeletal muscle tissues using northern-blot and RT-PCR analyses. In northern-blot analysis, two types (4.5 kb and 4.2 kb) of iNOS mRNA have been observed in retinal tissue, whereas only one type of mRNA was observed in cerebellum (4.5 kb) and skeletal muscle (4.2 kb). This result indicates that the presence of differential expression and/or structural diversity of the iNOS gene in various tissues, and some cells can express iNOS gene constitutively. We have also demonstrated a structural diversity formed by alternative splicing in the open reading frame sequence of the INOS cDNA cloned from retinal tissue, which may reflect functional differences of iNOS gene. C1 NHLBI,LAB MOLEC IMMUNOL,SECT CHEM PHARMACOL,BETHESDA,MD 20892. NR 30 TC 78 Z9 81 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 14 PY 1996 VL 59 IS 3 BP 219 EP 225 DI 10.1016/0024-3205(96)00287-1 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UQ743 UT WOS:A1996UQ74300004 PM 8699932 ER PT J AU Sherman, DR Mdluli, K Hickey, MJ Arain, TM Morris, SL Barry, CE Stover, CK AF Sherman, DR Mdluli, K Hickey, MJ Arain, TM Morris, SL Barry, CE Stover, CK TI Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis SO SCIENCE LA English DT Article ID OXIDATIVE STRESS AB Mutations that eliminate KatG catalase-peroxidase activity prevent activation of isoniazid and are a major mechanism of resistance to this principal drug for the treatment of Mycobacterium tuberculosis infections. However, the loss of KatG activity in clinical isolates seemed paradoxical because KatG is considered an important factor for the survival of the organism. Expression of either KatG or the recently identified alkyl hydroperoxidase AhpC was sufficient to protect bacilli against the toxic effects of organic peroxides. To survive during infection, isoniazid-resistant KatG mutants have apparently compensated for the loss of KatG catalase-peroxidase activity by a second mutation, resulting in hyperexpression of AhpC. C1 PATHOGENESIS CORP,LAB TB & MOL MICROBIOL,SEATTLE,WA 98119. NIAID,TB RES UNIT,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. US FDA,LAB MYCOBACTERIA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RI Barry, III, Clifton/H-3839-2012; OI Stover, Charles/0000-0002-7406-1696 FU Intramural NIH HHS [Z01 AI000783-11] NR 21 TC 272 Z9 288 U1 2 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 14 PY 1996 VL 272 IS 5268 BP 1641 EP 1643 DI 10.1126/science.272.5268.1641 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UR093 UT WOS:A1996UR09300043 PM 8658136 ER PT J AU Oda, N Levin, JD Spoonde, AY Frank, EG Levine, AS Woodgate, R Ackerman, EJ AF Oda, N Levin, JD Spoonde, AY Frank, EG Levine, AS Woodgate, R Ackerman, EJ TI Arrested DNA replication in Xenopus and release by Escherichia coli mutagenesis proteins SO SCIENCE LA English DT Article ID REPAIR; OOCYTES; EXTRACT; GENES; UMUD'; EGGS; RECA AB Xenopus oocytes and oocyte nuclear extracts repair ultraviolet photoproducts on double-stranded (ds) DNA and replicate single-stranded (ss) to ds DNA, M13 ss DNA molecules containing cyclobutane pyrimidine dimers were maintained but not replicated in Xenopus oocytes, yet were replicated in progesterone-matured oocytes, The replication arrest functioned only in cis, The replication arrest was alleviated by injection into oocytes of messenger RNAs encoding the prokaryotic mutagenesis proteins UmuD'C or MucA'B, These results may help explain how cells stabilize repair or replication events on DNA with unrepairable lesions. C1 NIDDKD,NIH,BETHESDA,MD 20892. NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. NR 31 TC 13 Z9 13 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 14 PY 1996 VL 272 IS 5268 BP 1644 EP 1646 DI 10.1126/science.272.5268.1644 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UR093 UT WOS:A1996UR09300044 PM 8658137 ER PT J AU Kitsukawa, Y Turner, RJ Pradhan, TK Jensen, RT AF Kitsukawa, Y Turner, RJ Pradhan, TK Jensen, RT TI Gastric chief cells possess NK1 receptors which mediate pepsinogen secretion and are regulated by agents that increase cAMP and phospholipase C SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE substance P; chief cell; pepsinogen release; receptor regulation ID PANCREATIC ACINAR-CELLS; SUBSTANCE-P RECEPTORS; GUINEA-PIG STOMACH; TACHYKININ RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; MOLECULAR CHARACTERIZATION; K RECEPTOR; INOSITOL PHOSPHATES; MESSENGER-RNAS; BINDING AB In order to determine whether tachykinins alter the function of chief cells and to characterize the receptors mediating the effect, we investigated the abilities of various substance P (SP)-related peptides to inhibit the binding of I-125-Bolton-Hunter labeled substance P (I-125-BH-SP) and their abilities to alter cell function in dispersed chief cells from guinea pig stomach. Binding of I-125-BH-SP was saturable, reversible, time- and temperature-dependent and was inhibited by several SP-related peptides with relative potencies of SP = physalaemin (IC50 : 0.19 nM) > SP methyl ester (SP-ME) (IC50 : 3.3 nM) > eledoisin (IC50 : 6.1 nM)> neurokinin A (NKA) (IC50 : 65 nM)> neurokinin B (NKB) (IC50 : 80 nM). Analyses of these binding data demonstrated that chief cells possess a high and low affinity class of binding sites. Neither I-125-NKA nor [phenylalanyl-3,4,5-H-3]senktide demonstrated saturable binding to chief cells. Acid stripping experiments demonstrated rapid ligand internalization with 55% of the bound radioligand internalized by 10 min. Phospholipase C activating agents (carbachol, CCK-8), adenylate cyclase activating agents (secretin, VIP), TPA and the calcium ionophore, A23187, all inhibited the binding of I-125-BH-SP and it was due to inhibition of ligand internalization with no change in surface bound parameters. SP (0.1 mu M) stimulated pepsinogen secretion but was 4-times less efficacious than CCK-8 (10 nM) or carbachol (1 mM), 10 nM SP stimulated a rapid increase in cytoplasmic free calcium concentration ([Ca2+](i)) followed by a sustained elevation lasting 2 min. Single cell spectroscopy demonstrated SP (10 pM to 1 mu M) did not cause calcium oscillations. The NK1 receptor antagonist, CP96,345 specifically inhibited the SP-stimulated changes in [Ca2+](i) and pepsinogen secretion. The relative potencies of SP-related peptides to stimulate pepsinogen secretion and [Ca2+](i) demonstrated a close agreement with their abilities to inhibit the binding of I-125-BH-SP, and comparison of the dose-response curves suggests occupation of the low affinity sites mediate changes in biologic activity. In conclusion, the present study demonstrates that chief cells possess a NK1 subtype of tachykinin receptor, occupation of the low affinity sites of this receptor cause calcium mobilization and pepsinogen secretion, and that binding to this receptor is regulated by agents that activate phospholipase C, adenylate cyclase, protein kinase C and calcium mobilization. C1 NIDDKD,NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIDR,NIH,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 53 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUN 13 PY 1996 VL 1312 IS 2 BP 105 EP 116 DI 10.1016/0167-4889(96)00026-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UU504 UT WOS:A1996UU50400005 PM 8672532 ER PT J AU Procacci, P Darden, T Marchi, M AF Procacci, P Darden, T Marchi, M TI A very fast molecular dynamics method to simulate biomolecular systems with realistic electrostatic interactions SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID MULTIPLE TIME SCALES; LONG-RANGE FORCES; SUMS AB In this paper we describe the implementation of a very fast molecular dynamic method to realistically handle electrostatic interactions in simulations of solvated proteins. Our scheme is based on a recently proposed reversible multiple time step (r-RESPA) algorithm and a new modification of the particle mesh Ewald method. While the latter technique provides a fast and accurate representation of the Coulombic interactions for infinite systems, the r-RESPA algorithm exploits a separation of the particle force into components with increasingly longer time scales corresponding to contributions from short-, medium-, and long-range radial shells, By combining the two techniques we are able to reduce considerably the computational cost of molecular dynamics simulation of large biomolecular system without affecting energy conservation and dynamical properties. With respect to single time step simulations employing standard Ewald summation and rigid bond constraints, we obtain a speed-up of about 1 order of magnitude, Finally, our method is about 2.5 times as fast as simulations making use of spherical cutoffs. Since the majority of today biomolecular simulations use spherical cutoffs, we expect that our algorithm will find general applications in the field. C1 CTR ETUD SACLAY,CEA,DSV,DBCM,SECT BIOPHYS PROT & MEMBRANES,F-91191 GIF SUR YVETTE,FRANCE. ECOLE NORMALE SUPER LYON,CECAM,F-69364 LYON,FRANCE. NIEHS,RES TRIANGLE PK,NC 27709. RI Marchi, Massimo/E-1792-2011; Procacci, Piero/D-7860-2012 OI Marchi, Massimo/0000-0003-4890-6349; Procacci, Piero/0000-0003-2667-3847 NR 27 TC 78 Z9 78 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUN 13 PY 1996 VL 100 IS 24 BP 10464 EP 10468 DI 10.1021/jp960295w PG 5 WC Chemistry, Physical SC Chemistry GA UQ844 UT WOS:A1996UQ84400062 ER PT J AU Margulies, DH AF Margulies, DH TI Immunology - An affinity for learning SO NATURE LA English DT Editorial Material RP Margulies, DH (reprint author), NIAID,MOLEC BIOL SECT,IMMUNOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 11 TC 13 Z9 13 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 13 PY 1996 VL 381 IS 6583 BP 558 EP 559 DI 10.1038/381558a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ657 UT WOS:A1996UQ65700023 PM 8637586 ER PT J AU Ernst, M Zametkin, AJ Matochik, JA Pascualvaca, D Jons, PH Hardy, K Hankerson, JG Doudet, DJ Cohen, RM AF Ernst, M Zametkin, AJ Matochik, JA Pascualvaca, D Jons, PH Hardy, K Hankerson, JG Doudet, DJ Cohen, RM TI Presynaptic dopaminergic deficits in Lesch-Nyhan disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; F-18 DOPA; PARKINSONS-DISEASE; BRAIN; MODEL; BEHAVIOR; NEUROTRANSMITTERS; CARBIDOPA; MONKEYS AB Background. Lesch-Nyhan disease is a rare, devastating, X-linked recessive disorder of purine synthesis. Patients present with hyperuricemia, choreoathetosis, dystonia, and aggressive and self-injurious behavior. Although the genetic and biochemical abnormalities have been identified, the causes of the neuropsychiatric syndrome remain unclear. Methods. We used positron-emission tomography to measure presynaptic accumulation of fluorodopa F 18 tracer in the dopaminergic regions of the brains of 12 patients with Lesch-Nyhan disease (age, 10 to 20 years) and 15 healthy controls (age, 12 to 23). The results were expressed as ratios of specific to nonspecific radioactive counts. A low ratio indicates decreased dopa decarboxylase activity and dopamine storage. Results. The fluorodopa F 18 ratio was significantly lower in the putamen (31 percent of control values), caudate nucleus (39 percent), frontal cortex (44 percent), and ventral tegmental complex (substantia nigra and ventral tegmentum; 57 percent) in the patients with Lesch-Nyhan disease than in the controls. Uptake of the tracer was abnormally low even in the youngest patients tested, and there was no overlap in the values between patients and controls. Conclusions. Patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggests that they contribute to the characteristic neuropsychiatric manifestations of the disease. (C) 1996, Massachusetts Medical Society. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT ANESTHESIOL,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. RP Ernst, M (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,CONVENT DR,MSC 4030,BETHESDA,MD 20892, USA. NR 39 TC 116 Z9 117 U1 1 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 13 PY 1996 VL 334 IS 24 BP 1568 EP 1572 DI 10.1056/NEJM199606133342403 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UP663 UT WOS:A1996UP66300003 PM 8628337 ER PT J AU Yamasaki, H Ashby, J Bignami, M Jongen, W Linnainmaa, K Newbold, RF NguyenBa, G Parodi, S Rivedal, E Schiffmann, D Simons, JWIM Vasseur, P AF Yamasaki, H Ashby, J Bignami, M Jongen, W Linnainmaa, K Newbold, RF NguyenBa, G Parodi, S Rivedal, E Schiffmann, D Simons, JWIM Vasseur, P TI Nongenotoxic carcinogens: Development of detection methods based on mechanisms: A European project SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE risk assessment; cell transformation; intercellular communication; cell immortalization; cell proliferation; structure-activity relationship ID JUNCTIONAL INTERCELLULAR COMMUNICATION; HAMSTER EMBRYO CELLS; DIFFERENTIAL SCANNING CALORIMETRY; TPA-INDUCED INHIBITION; MORPHOLOGICAL TRANSFORMATION; CHEMICAL-STRUCTURE; IN-VITRO; GAP; MUTAGENICITY; CANCER AB While the accumulation of genetic changes in a somatic cell is considered essential for the genesis of a cancer, it has become clear that not all carcinogens are genotoxic, suggesting that some carcinogens indirectly participate in the generation of genetic changes during carcinogenesis, A European project funded by the European Community was thus conceived to study mechanisms of nongenotoxic aspects of carcinogenesis, Two main strategical approaches were adapted: (i) to study whether and how Syrian hamster embryo (SHE), Syrian hamster dermal (SHD) and BALB/c 3T3 cell transformation systems simulate in vivo carcinogenesis, and to examine whether they can detect nongenotoxic carcinogens; (ii) to study, refine and validate mechanisms-based end-points for detection of nongenotoxic carcinogens. For mechanisms-based research, the proposed end-points included gap junctional intercellular communication (GJIC) inhibition, altered expression of critical genes, immortalization and aberrant cell proliferation. We also selected model compounds commonly usable for various endpoints. Our major results can be summarized as follows: (1) SHE and BALB/c 3T3 transformation systems reflect both genotoxic and nongenotoxic carcinogenic events; they detect not only genotoxic but also many although not all, nongenotoxic carcinogens. This is further supported by the fact that both genotoxic and nongenotoxic carcinogens were able to immortalize SHD cells. (2) Many nongenotoxic carcinogens, although not all, inhibit GJIC in vitro as well as in vivo. Mechanistic studies suggest an important role of blocked GJIC in carcinogenesis and that different mechanisms are involved in inhibition of the communication by different agents used. However, inhibition of GJIC is not a prerequisite for the enhancement (or induction) of transformation of SHE or BALB/c 3T3 cells. (3) Among compounds examined, there was a good correlation between induction of micronuclei and cell transformation in SHE cells while no such correlation was found between the induction of cell transformation and ornithine decarboxylase activity. (4) Two transgenic mouse mutation assays (lacI and lacZ) were established and validated. The genotoxin dimethylnitrosamine was shown to be mutagenic to the liver in both assays. Ortho-anisidine, a bladder-specific carcinogen that was inactive in standard rodent genetic toxicity assays was uniquely mutagenic to the bladder of the transgenic mice. The peroxisome proliferator methyl clofenipate was established as nonmutagenic to the liver of both transgenic mice. That eliminated DNA damage as a cause of the liver tumours produced by this chemical and weakened the idea that induced cell division leads to mutation induction. (5) With an in vitro DNA replication model, it was found that DNA damage induced by genotoxic agents can be responsible for inhibition of DNA replication, while certain nongenotoxic agents such as phorbol esters increase DNA replication. (6) An attempt to use structure-activity relationship for subfamilies of nongenotoxic carcinogens, e.g., receptor-mediated carcinogens, has been initiated with some promising results. Our results support the idea that there are multiple nongenotoxic mechanisms in carcinogenesis, and that working hypothesis-oriented approaches are encouraged rather than simple screening of chemicals in developing test systems for the detection of nongenotoxic carcinogens. C1 ZENECA CENT TOXICOL LAB,MACCLESFIELD,CHESHIRE,ENGLAND. IST SUPER SANITA,I-00161 ROME,ITALY. AGROTECH RES INST,NL-6700 AA WAGENINGEN,NETHERLANDS. INST OCCUPAT HLTH,SF-00250 HELSINKI,FINLAND. BRUNEL UNIV,UXBRIDGE UB8 3PH,MIDDX,ENGLAND. INST CANCEROL & IMMUNOGENET,F-94800 VILLEJUIF,FRANCE. NATL CANC INST,I-16132 GENOA,ITALY. NORWEGIAN RADIUM HOSP,INST CANC RES,N-0310 OSLO 3,NORWAY. UNIV ROSTOCK,D-18051 ROSTOCK,GERMANY. LEIDEN UNIV,NL-2333 AL LEIDEN,NETHERLANDS. CTR ENVIRONM SCI,F-57040 METZ,FRANCE. RP Yamasaki, H (reprint author), INT AGCY RES CANC,150 COURS ALBERT THOMAS,F-69372 LYON 08,FRANCE. NR 74 TC 56 Z9 56 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 JUN 12 PY 1996 VL 353 IS 1-2 BP 47 EP 63 DI 10.1016/0027-5107(95)00241-3 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA UU606 UT WOS:A1996UU60600003 PM 8692192 ER PT J AU Zlotnick, A Cheng, N Conway, JF Booy, FP Steven, AC Stahl, SJ Wingfield, PT AF Zlotnick, A Cheng, N Conway, JF Booy, FP Steven, AC Stahl, SJ Wingfield, PT TI Dimorphism of hepatitis B virus capsids is strongly influenced by the C-terminus of the capsid protein SO BIOCHEMISTRY LA English DT Article ID HERPES-SIMPLEX VIRUS; ELECTRON-MICROSCOPY; ESCHERICHIA-COLI; SIMIAN VIRUS-40; CORE PROTEIN; RNA; ANTIGEN; RECONSTRUCTION; POLYMERASE; EXPRESSION AB Hepatitis B virus (HBV) is an enveloped virus with an icosahedral capsid. Its homodimeric capsid protein (''core antigen'') assembles into particles of two sizes, one with T = 3 icosahedral symmetry (90 dimers) and the other with T = 4 symmetry (120 dimers). We have investigated this assembly process in vitro, using a variety of purified, bacterially expressed, capsid proteins. All of our constructs lacked the predominantly basic C-terminal 34 amino acids of the full-length capsid protein (183 amino acids) and were further truncated to terminate at specific points between residues 138 and 149. While the smallest construct (138 residues) did not assemble into capsids, those terminating at residue 140, and beyond, assembled into mixtures of T = 3 and T = 4 particles. The two kinds of capsids could be separated on sucrose gradients and did not interconvert upon protracted storage. The proportion of T = 3 capsids, assayed by sucrose gradient fractionation, analytical ultracentrifugation and cryoelectron microscopy, was found to increase systematically with larger deletions from the C-terminus. The variant terminating at residue 149 formed similar to 5% of T = 3 capsids, while the 140-residue protein produced similar to 85% of this isomorph. For the 147-residue capsid protein, the structures of both capsids were determined to 17 Angstrom resolution by three-dimensional reconstruction of cryoelectron micrographs. In these density maps, the boundaries of the constituent dimers can be clearly seen and the quaternary structures of the two capsids compared. The arrangement of dimers around their icosahedral five-fold axes is almost identical, whereas the quasi-six-fold arrangements of dimers are distinctly different. C1 NIAMSD,STRUCT BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 51 TC 169 Z9 183 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 11 PY 1996 VL 35 IS 23 BP 7412 EP 7421 DI 10.1021/bi9604800 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ525 UT WOS:A1996UQ52500013 PM 8652518 ER PT J AU Said, HM Nguyen, TT Dyer, DL Cowan, KH Rubin, SA AF Said, HM Nguyen, TT Dyer, DL Cowan, KH Rubin, SA TI Intestinal folate transport, identification of a cDNA involved in folate transport and the functional expression and distribution of its mRNA SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE intestinal folate transport; folate transport; cDNA library; DNA sequencing; (Xenopus oocyte) ID BRUSH-BORDER MEMBRANE; FOLIC-ACID ABSORPTION; JEJUNAL PERFUSION; RAT; MALABSORPTION; EXCHANGE; VESICLES; PROTEIN; SPRUE AB Although the mechanism of folate intestinal transport has been the subject of intensive studies, very little is known about the molecular identity of the transport system(s) involved. In this investigation, we screened a mouse intestinal cDNA library using as probe the cDNA clone of a reduced folate carrier (RFC1) of mouse leukemia L1210 cells, and identified a positive clone, IFC1(RFC1). The cloned cDNA consisted of 2274 base pairs with an open reading frame that encodes a putative polypeptide of 512 amino acids with a predicted molecular mass of 58 112 daltons and 12 putative transmembrane domains. The polypeptide appears to carry a net positive charge (pI = 8.6) which may be important for its interaction with the negatively charged substrate. Functional identity of the IFC1(RFC1) clone was established by expression in Xenopus oocytes. An 11-fold increase in 5-methyltetrahydrofolate (5-MTHF) uptake was observed in oocytes injected with 10 ng IFC1(RFC1) cRNA compared to water-injected controls. The expressed folate uptake in the cRNA injected oocyte was: (1) 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive; and (2) saturable with an apparent K-m of 1.99 +/- 0.32 mu M, and a V-max of 3782 +/- 188 fmol/oocyte per h. The distribution of mRNA species complementary to IFC1(RFC1) in different mouse tissues was examined by Northern blot analysis. In addition to the small intestine, expression of such mRNA species were also found in the kidney, large intestine, brain, heart and liver. Furthermore, mRNA species complementary to IFC1(RFC1) were also detected by Northern blot analysis in the small intestine of human and other animal species (rat and rabbit). Expression of mRNA complementary to IFC1(RFC1) was markedly higher in rat intestinal villus cells than in crypt cells. These results represent the first identification of a folate transporter in mammalian intestine. C1 UNIV CALIF IRVINE,CALIF COLL MED,DEPT MED,IRVINE,CA 92717. UNIV CALIF IRVINE,CALIF COLL MED,DEPT PEDIAT,IRVINE,CA 92717. UNIV CALIF IRVINE,CALIF COLL MED,DEPT PHYSIOL BIOPHYS,IRVINE,CA 92717. NCI,NIH,BETHESDA,MD 20892. RP Said, HM (reprint author), VET AFFAIRS MED CTR,151,5901 E 7TH ST,LONG BEACH,CA 90822, USA. FU NIDDK NIH HHS [DK47203, IF32 DK09040] NR 46 TC 70 Z9 73 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JUN 11 PY 1996 VL 1281 IS 2 BP 164 EP 172 DI 10.1016/0005-2736(96)00005-3 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UQ956 UT WOS:A1996UQ95600007 PM 8664315 ER PT J AU Monini, P Rotola, A deLellis, L Corallini, A Secchiero, P Albini, A Benelli, R Parravicini, C BarbantiBrodano, G Cassai, E AF Monini, P Rotola, A deLellis, L Corallini, A Secchiero, P Albini, A Benelli, R Parravicini, C BarbantiBrodano, G Cassai, E TI Latent BK virus infection and Kaposi's sarcoma pathogenesis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMORS AB We have analyzed by PCR skin lesions from classic, endemic and AIDS-related Kaposi's sarcoma (KS), as well as from KS-derived cell lines, the presence of ubiquitous transforming viruses. BK virus (BKV), a transforming human papovavirus which has been associated with human tumors, was detected in 100% of KS skin lesions and 75% of KS cell lines. KS specimens contained a full-length, intact BKV early region, but minor rearrangements were observed in some tumors. BKV was also detected with a high prevalence (57-67%) in genital tissues and sperm, thus fulfilling the role of a sexually transmitted agent in KS. The closely related JC virus (ICV), which has never been associated with human malignancies, was present in 11-20% of KS specimens and was detected with a low prevalence (0-21%) in genital tissues and sperm. Simian virus 40 (SV40) was not detected in any KS lesions. Herpes simplex virus (HSV) DNA sequences were detected in 20-25% of KS lesions. Malignant human papillomavirus (HPV) types 16 and 18 and benign HPV types 6 and 11 were detected in KS specimens with a similar prevalence of 11-83%, suggesting that the presence of HPV-transforming sequences is not a specific trait of HPV interaction with KS tissue. Furthermore, JCV, SV40, HSV and HPV DNA sequences were not detected in KS cell lines, suggesting that these viruses are not associated to KS neoplastic cells in KS tissue. KS cell lines were also negative for DNA sequences of KS-HV, the novel herpesvirus detected in primary KS lesions. The constant association of BKV DNA with KS lesions and KS cell lines suggests that BKV-transforming functions may participate in the development of KS. (C) 1996 Wiley-Liss, Inc. C1 UNIV FERRARA,SCH MED,INST MICROBIOL,I-44100 FERRARA,ITALY. UNIV FERRARA,INTERDEPT CTR BIOTECHNOL,I-44100 FERRARA,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NATL INST CANC RES,GENOA,ITALY. UNIV MILAN,LUIGI SACCO HOSP,DEPT PATHOL ANAT & HISTOL,MILAN,ITALY. RI secchiero, paola/G-9689-2015; Monini, Paolo/K-1429-2016 OI secchiero, paola/0000-0003-4101-7987; Monini, Paolo/0000-0002-4941-6854 NR 24 TC 68 Z9 68 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 JUN 11 PY 1996 VL 66 IS 6 BP 717 EP 722 DI 10.1002/(SICI)1097-0215(19960611)66:6<717::AID-IJC1>3.0.CO;2-2 PG 6 WC Oncology SC Oncology GA UP063 UT WOS:A1996UP06300001 PM 8647638 ER PT J AU Schlehofer, B Pommer, W Mellemgaard, A Stewart, JH McCredie, M Niwa, S Lindblad, P Mandel, JS McLaughlin, JK Wahrendorf, J AF Schlehofer, B Pommer, W Mellemgaard, A Stewart, JH McCredie, M Niwa, S Lindblad, P Mandel, JS McLaughlin, JK Wahrendorf, J TI International renal-cell-cancer study .6. The role of medical and family history SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; RISK-FACTORS; DIALYSIS PATIENTS; CARCINOMA; CALCIUM; STONES AB A number of medical conditions have been linked with renal-cell cancer, although the evidence is not consistent in every case. In a large international case-control study of renal-cell cancer, we examined, among other hypotheses, associations with a personal history of certain medical conditions and a family history of cancer of the kidney or thyroid. Relative risks (RR), adjusted for the effects of age, gender, body-mass index, tobacco smoking and study centre, were significantly increased by a history of kidney stones or thyroid or kidney disease. The RR were not altered by additional adjustment for hypertension, or when diagnoses were restricted to those made at least 5 or 10 years before 1987 (the usual ''cut-off'' date). The link with kidney injury is particularly likely to be affected by recall bias. Increased RR of borderline significance were found for kidney infection (RR, 1.2) and diabetes (RR, 1.4). Having one first-degree relative with kidney cancer was associated with a significantly increased risk of renal-cell cancer(RR, 1.6; 95% CI, 1.1-2.4). Seven cases reported 2 first-degree relatives with kidney cancer. No controls had first-degree relatives with kidney cancer. None of our participants reported having von Hippel-Lindau disease. The data suggests that a few conditions of the kidney are strongly associated with renal-cell cancer and that heredity plays a role in a small proportion of cases. (C) 1996 Wiley-Liss, Inc. C1 HUMBOLDT HOSP,BERLIN,GERMANY. DANISH CANC SOC,DANISH CANC REGISTRY,COPENHAGEN,DENMARK. UNIV SYDNEY,WESTERN CLIN SCH,SYDNEY,NSW,AUSTRALIA. NSW CANC COUNCIL,CANC EPIDEMIOL RES UNIT,SYDNEY,NSW,AUSTRALIA. WESTAT CORP,ROCKVILLE,MD. UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. RP Schlehofer, B (reprint author), DEUTSCH KREBSFORSCHUNGSZENTRUM,DIV EPIDEMIOL,NEUENHEIMER FELD 280,D-69120 HEIDELBERG,GERMANY. NR 34 TC 66 Z9 66 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 JUN 11 PY 1996 VL 66 IS 6 BP 723 EP 726 DI 10.1002/(SICI)1097-0215(19960611)66:6<723::AID-IJC2>3.0.CO;2-1 PG 4 WC Oncology SC Oncology GA UP063 UT WOS:A1996UP06300002 PM 8647639 ER PT J AU Kollia, P Fibach, E Najjar, SM Schechter, AN Noguchi, CT AF Kollia, P Fibach, E Najjar, SM Schechter, AN Noguchi, CT TI Modifications of RNA processing modulate the expression of hemoglobin genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EPSILON-GLOBIN GENE; POLYMERASE CHAIN-REACTION; CELL-FREE SYSTEM; MESSENGER-RNA; LINE K562; TRANSCRIPTION; DIFFERENTIATION; SILENCER; REGION; STABILITY AB The developmental changes in hemoglobin gene expression known as ''switching'' involve both the sequential activation and silencing of the individual globin genes. We postulated that in addition to changes in transcription, posttranscriptional mechanisms may be involved in modulating globin gene expression. We studied globin RNA transcripts in human adult erythroid cells (hAEC) to analyze the mechanism of silencing of the embryonic epsilon-globin gene in the adult stage and in K562 erythroleukemic cells to analyze the inactive state of their adult beta-globin genes, In hAEC, which express primarily the beta-globin gene, quantitative PCR analysis shows that beta-mRNA exon levels are high and comparable among the three exons; the RNA transcripts corresponding to exons of the gamma-globin gene are low, with slight differences among the three exons. Although epsilon-globin is not expressed, epsilon-globin RNA transcripts are detected, with exon I levels comparable to that of gamma-globin exon I and much higher than epsilon-exons II and III. As expected, in K562 cells that express high levels of epsilon- and gamma-globin, epsilon- and gamma-mRNA levels are high, with comparable levels of exons I, II, and III. In K562 cells beta-mRNA levels are very low but beta-exon I levels are much higher than that of exons II or III, Moreover, all or most of the globin transcripts for the highly expressed globin genes in both cell types (gamma and beta in hAEC, epsilon and gamma in K562 cells) found in the cytoplasm or nucleus are correctly processed, The globin transcripts that are detected both in the cytoplasm and nucleus of cells without expression of the corresponding protein are largely unspliced (containing one or two intervening sequences). These studies suggest that in addition to changes in transcription rates, changes in completion or processing of globin RNA transcripts may contribute to the developmental regulation of the hemoglobin phenotype. C1 NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. OI Schechter, Alan N/0000-0002-5235-9408 NR 38 TC 15 Z9 16 U1 1 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 JUN 11 PY 1996 VL 93 IS 12 BP 5693 EP 5698 DI 10.1073/pnas.93.12.5693 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500005 PM 8650154 ER PT J AU Yim, MB Kang, JH Yim, HS Kwak, HS Chock, PB Stadtman, ER AF Yim, MB Kang, JH Yim, HS Kwak, HS Chock, PB Stadtman, ER TI A gain-of-function of an amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutant: An enhancement of free radical formation due to a decrease in K-m for hydrogen peroxide SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE spin trapping; electron paramagnetic resonance; recombinant enzyme; site-directed mutagenesis ID ZINC SUPEROXIDE-DISMUTASE; COPPER; INACTIVATION; METABOLISM; ENZYME AB Cu,Zn-superoxide dismutase (SOD) is known to be a locus of mutation in familial amyotrophic lateral sclerosis (FALS). Transgenic mice that express a mutant Cu,Zn-SOD, Gly-93 --> Ala (G93A), have been shown to develop amyotrophic lateral sclerosis (ALS) symptoms. We cloned the FALS mutant, G93A, and wild-type cDNA of human Cu,Zn-SOD, overexpressed them in Sf9 insect cells, purified the proteins, and studied their enzymic activities for catalyzing the dismutation of superoxide anions and the generation of free radicals with H2O2 as substrate. Our results showed that both enzymes contain one copper ion per subunit and have identical dismutation activity. However, the free radical-generating function of the G93A mutant, as measured by the spin trapping method, is enhanced relative to that of the wild-type enzyme, particularly at lower H2O2 concentrations. This is due to a small, but reproducible, decrease in the value of K-m for H2O2 for the G93A mutant, while the k(cat) is identical for both enzymes. Thus, the ALS symptoms observed in G93A transgenic mice are not caused by the reduction of Cu,Zn-SOD activity with the mutant enzyme; rather, it is induced by a gain-of-function, an enhancement of the free radical-generating function. This is consistent with the x-ray crystallographic studies showing the active channel of the FALS mutant is slightly larger than that of the wild-type enzyme; thus, it is more accessible to H2O2. This gain-of-function, in part, may provide an explanation for the association between ALS and Cu,Zn-SOD mutants. C1 CHEONGJU UNIV,DEPT GENET ENGN,CHEONGJU,SOUTH KOREA. PAI CHAI UNIV,DEPT GENET ENGN,TAEJON,SOUTH KOREA. RP Yim, MB (reprint author), NHLBI,BIOCHEM LAB,NIH,BLDG 3,ROOM 202,BETHESDA,MD 20892, USA. NR 30 TC 393 Z9 398 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 5709 EP 5714 DI 10.1073/pnas.93.12.5709 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500008 PM 8650157 ER PT J AU Tomonaga, T Levens, D AF Tomonaga, T Levens, D TI Activating transcription from single stranded DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heterogeneous nuclear ribonucleoprotein K; CT element; c-myc; DNA supercoiling; gene regulation ID LARGE T-ANTIGEN; C-MYC; PROTEIN; BINDING; PROMOTER; EXPRESSION; CONFORMATION; TOPOLOGY; ELEMENTS; REGIONS AB Sequence specific regulators of eukaryotic gene expression, axiomatically, act through double stranded DNA targets, Proteins that recognize DNA cis-elements as single strands but for which compelling evidence has been lacking to indicate in vivo involvement in transcription are orphaned in this scheme, We sought to determine whether sequence specific single strand binding proteins can find their cognate elements and modify transcription in vivo by studying heterogeneous nuclear ribonucleoprotein Ii (hnRNP Ii), which binds the single stranded sequence (CCCTCCCCA; CT-element) of the human c-myc gene in vitro, To monitor its DNA binding in vivo, the ability of hnRNP K to activate a reporter gene was amplified by fusion with the VP16 transactivation domain, This chimeric protein was found to transactivate circular but not linear CT-element driven reporters, suggesting that hnRNP ii recognizes a single strand region generated by negative supercoiling in circular plasmid, When CT-elements were engineered to overlap with lexA operators, addition of lexA protein, either in vivo or in vitro, abrogated hnRNP ii binding most likely, by preventing single strand formation, These results not only reveal hnRNP K to be a single strand DNA binding protein in vivo, but demonstrate how a segment of DNA mag modify the transcriptional activity of an adjacent gene through the interconversion of duplex and single strands. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 37 TC 137 Z9 139 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 JUN 11 PY 1996 VL 93 IS 12 BP 5830 EP 5835 DI 10.1073/pnas.93.12.5830 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500030 PM 8650178 ER PT J AU Lakso, M Pichel, JG Gorman, JR Sauer, B Okamoto, Y Lee, E Alt, FW Westphal, H AF Lakso, M Pichel, JG Gorman, JR Sauer, B Okamoto, Y Lee, E Alt, FW Westphal, H TI Efficient in vivo manipulation of mouse genomic sequences at the zygote stage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transgenic; Cre recombinase; loxP ID SITE-SPECIFIC RECOMBINATION; TRANSGENIC MICE; ONCOGENE ACTIVATION; DNA RECOMBINATION; CRE RECOMBINASE; CELLS; LENS AB We describe a transgenic mouse line carrying the cre transgene under the control of the adenovirus EIIa promoter that targets expression of the Cre recombinase to the early mouse embryo, To assess the ability of this recombinase to excise loxP-flanked DNA sequences at early stages of of development, we bred EIIa-cre transgenic mice to two different mouse lines carrying loxP-flanked target sequences: (i) a strain with a single gene-targeted neomycin resistance gene flanked by loxP sites and (ii) a transgenic line carrying multiple transgene copies with internal loxP sites, Mating either of these lowP-carrying mouse lines to EIIa-cre mice resulted in first generation progeny in which the loxP-flanked sequences had been efficiently deleted from all tissues tested, including the germ cells, Interbreeding of these first generation progeny resulted in efficient germ-line transmission of the deletion to subsequent generations, These results demonstrate a method by which loxP-flanked DNA sequences can,be efficiently deleted in the early mouse embryo, Potential applications of this approach are discussed, including reduction of multicopy transgene loci to produce single-copy transgenic lines and introduction of a variety of subtle mutations into the germ line. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU PHS HHS [A.I.20047, A.I.31541] NR 19 TC 697 Z9 699 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 5860 EP 5865 DI 10.1073/pnas.93.12.5860 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500035 PM 8650183 ER PT J AU Takayama, H LaRochelle, WJ Anver, M Bockman, DE Merlino, G AF Takayama, H LaRochelle, WJ Anver, M Bockman, DE Merlino, G TI Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE melanocytes; Met; migration; transgenic mice; TRP-2 ID TRANSGENIC MICE; MET; DIFFERENTIATION; NOTOCHORD; RECEPTOR; MITOGEN AB Factors that regulate cellular migration during embryonic development are essential for tissue and organ morphogenesis. Scatter factor/hepatocyte growth factor (SF/HGF) can stimulate motogenic and morphogenetic activities in cultured epithelial cells expressing the Met tyrosine kinase receptor and is essential for development; however, the precise physiological role of SF/HGF is incompletely understood. Here we provide functional evidence that inappropriate expression of SF/HGF in transgenic mice influences the development of two distinct migratory cell lineages, resulting in ectopic skeletal muscle formation and melanosis in the central nervous system, and patterned hyperpigmentation of the skin, Committed TRP-2 positive melanoblasts were found to be situated aberrantly within defined regions of the transgenic embryo, including the neural tube, which overproduced SF/HGF. Our data strongly suggest that SF/HGF possesses physiologically relevant scatter activity, and functions as a true morphogenetic factor by regulating migration and/or differentiation of select populations of premyogenic and neural crest cells during normal mammalian embryogenesis. C1 NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. MED COLL GEORGIA,DEPT CELLULAR BIOL & ANAT,AUGUSTA,GA 30912. NR 38 TC 152 Z9 155 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 JUN 11 PY 1996 VL 93 IS 12 BP 5866 EP 5871 DI 10.1073/pnas.93.12.5866 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500036 PM 8650184 ER PT J AU Bottinger, EP Factor, VM Tsang, MLS Weatherbee, JA Kopp, JB Qian, SW Wakefield, LM Roberts, AB Thorgeirsson, SS Sporn, MB AF Bottinger, EP Factor, VM Tsang, MLS Weatherbee, JA Kopp, JB Qian, SW Wakefield, LM Roberts, AB Thorgeirsson, SS Sporn, MB TI The recombinant proregion of transforming growth factor beta 1 (Latency-associated peptide) inhibits active transforming growth factor beta 1 in transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOLECULAR-WEIGHT COMPLEX; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; TGF-BETA; BINDING-PROTEIN; HUMAN-PLATELETS; FACTOR-BETA-1; ACTIVATION; PRECURSOR; RECEPTOR AB All three isoforms of transforming growth factors beta (TGF-beta 1, TGF-beta 2, and TGF-beta 3) are secreted as latent complexes and activated extracellularly, leading to the release of the mature cytokines from their noncovalently associated proregions, also known as latency-associated peptides (LAPs), The LAP region of TGF-beta 1 was expressed in a baculovirus expression system and purified to homogeneity. In vitro assays of growth inhibition and gene induction mediated by TGF-beta demonstrate that recombinant TGF-beta 1 LAP is a potent inhibitor of the activities of TGF-beta 1, -beta 2, and -beta 3, Effective dosages of LAP for 50% neutralization of TGF-beta activities range from 4.7- to 80-fold molar excess depending on the TGF-beta isoform and activity examined. Using (125)-labeled LAP, we show that the intraperitoneal application route is effective for systemic administration of LAP, Comparison of concentrations of LAP in tissues shows a homogenous pattern in most organs with the exception of heart and muscle, in which levels of LAP are 4- to I-fold lower, In transgenic mice with elevated hepatic levels of bioactive TGF-beta 1, treatment with recombinant LAP completely reverses suppression of the early proliferative response induced by TGF-beta 1 in remnant livers after partial hepatectomy. The results suggest that recombinant LAP is a potent inhibitor of bioactive TGF-beta both in vitro and in vivo, after intraperitoneal administration, Recombinant LAP should be a useful tool for novel approaches to study and therapeutically modulate pathophysiological processes mediated by TGF-beta. C1 NCI,EXPTL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. R&D SYST,MINNEAPOLIS,MN 55413. NIDDKD,KIDNEY DIS SECT,NIH,BETHESDA,MD 20892. RP Bottinger, EP (reprint author), NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892, USA. NR 59 TC 113 Z9 115 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 5877 EP 5882 DI 10.1073/pnas.93.12.5877 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500038 PM 8650186 ER PT J AU Anderson, SM Yu, G Giattina, M Miller, JL AF Anderson, SM Yu, G Giattina, M Miller, JL TI Intercellular transfer of a glycosylphosphatidylinositol (GPI)-linked protein: Release and uptake of CD4-GPI from recombinant adeno-associated virus-transduced HeLa cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DECAY-ACCELERATING FACTOR; FACTOR DAF; ENVELOPE GLYCOPROTEIN; ALKALINE-PHOSPHATASE; SIGNAL TRANSDUCTION; TYROSINE KINASES; SURFACE; CD4; EXPRESSION; INFECTION AB A diverse group of GPI-anchored protein structures are ubiquitously expressed on the external cell membranes of eukaryotes. Whereas the physiological role for these structures is usually defined by their protein component, the precise biological significance of the glycolipid anchors remains vague. In the course of producing a HeLa cell line (JM88) that contained a recombinant adeno-associated virus genome expressing a GPI-anchored CD4-GPI fusion protein on the surface of the cells, we noted the transfer of CD4-GPI to native HeLa cells, Transfer occurred after direct cell contact or exposure to JM88 cell supernatants. The magnitude of contact-mediated CD4-GPI transfer correlated with temperature. Supernatant CD4-GPI also attached to human red blood cells and could be cleaved with phosphatidylinositol-specific phospholipase C. The attached CD4-GPI remained biologically active after transfer and permitted the formation of syncytium when coated HeLa cells were incubated with glycoprotein 160 expressing H9 cells. JM88 cells provide a model for the production, release, and reattachment of CD4-GPI and may furnish insight into a physiologic role of naturally occurring GPI-anchored proteins. This approach may also allow the production of other recombinant GPI-anchored proteins for laboratory and clinical investigation. C1 NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 36 TC 41 Z9 42 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 JUN 11 PY 1996 VL 93 IS 12 BP 5894 EP 5898 DI 10.1073/pnas.93.12.5894 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500041 PM 8650189 ER PT J AU Shi, JS Ross, CR Leto, TL Blecha, F AF Shi, JS Ross, CR Leto, TL Blecha, F TI PR-39, a proline-rich antibacterial peptide that inhibits phagocyte NADPH oxidase activity by binding to Src homology 3 domains of p47(phox) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neutrophil; superoxide anion; cytochrome b(558); p22(phox) ID PIG INTESTINE; PROTEIN; HIV-1 AB Reactive oxygen intermediates generated by the phagocyte NADPH oxidase are critically important components of host defense, However, these highly toxic oxidants can cause significant tissue injury during inflammation; thus, it is essential that their generation and inactivation are tightly regulated, We show here that an endogenous proline-arginine (PR)-rich antibacterial peptide, PR-39, inhibits NADPH oxidase activity by blocking assembly of this enzyme through interactions with Src homology 3 domains of a cytosolic component. This neutrophil-derived peptide inhibited oxygen-dependent microbicidal activity of neutrophils in whole cells and in a cell-free assay of NADPH oxidase, Both oxidase inhibitory and direct antimicrobial activities were defined within the amino-terminal 26 residues of PR-39, Oxidase inhibition was attributed to binding of PR-39 to the p47(phox) cytosolic oxidase component, Its effects involve both a polybasic amino-terminal segment and a proline-rich core region of PR-39 that binds to the p47(phox) Src, homology 3 domains and, thereby, inhibits interaction with the smalt subunit of cytochrome b(558), p22(phox) These findings suggest that PR-39, which has been shown to be involved in tissue repair processes, is a multifunctional peptide that can regulate NADPH oxidase production of superoxide anion (0(2)(.-)), thus limiting excessive tissue damage during inflammation. C1 KANSAS STATE UNIV,COLL VET MED,DEPT ANAT & PHYSIOL,MANHATTAN,KS 66506. NIAID,NIH,HOST DEF LAB,BETHESDA,MD 20892. NR 39 TC 149 Z9 157 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 6014 EP 6018 DI 10.1073/pnas.93.12.6014 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500063 PM 8650211 ER PT J AU Huang, W Palyka, I Li, HF Eisenstein, EM Volkow, ND Springer, CS AF Huang, W Palyka, I Li, HF Eisenstein, EM Volkow, ND Springer, CS TI Magnetic resonance imaging (MRI) detection of the murine brain response to light: Temporal differentiation and negative functional MRI changes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN VISUAL-CORTEX; CHANNELS; SYSTEM; MONKEY AB Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings, (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex, another area displays decreased signal intensity upon stimulation. C1 SUNY STONY BROOK,DEPT RADIOL,STONY BROOK,NY 11794. VET AFFAIRS MED CTR,DEPT RADIOL,NORTHPORT,NY 11768. BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973. BROOKHAVEN NATL LAB,DEPT MED,UPTON,NY 11973. NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. RP Huang, W (reprint author), SUNY STONY BROOK,DEPT CHEM,STONY BROOK,NY 11794, USA. FU NIGMS NIH HHS [GM 32125] NR 41 TC 43 Z9 43 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 6037 EP 6042 DI 10.1073/pnas.93.12.6037 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500067 PM 8650215 ER PT J AU Bearer, EL DeGiorgis, JA Jaffe, H Medeiros, NA Reese, TS AF Bearer, EL DeGiorgis, JA Jaffe, H Medeiros, NA Reese, TS TI An axoplasmic myosin with a calmodulin-like light chain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SQUID LOLIGO-PEALEI; HIGH-AFFINITY; ORGANELLE MOVEMENT; SEQUENCE-ANALYSIS; MUSCLE MYOSINS; OPTIC LOBE; PROTEIN; KINESIN; BINDING; MICROTUBULES AB Organelles in the axoplasm from the squid giant axon move along exogenous actin filaments toward their barbed ends. An approximate to 235-kDa protein, the only band recognized by a pan-myosin antibody in Western blots of isolated axoplasmic organelles, has been previously proposed to be a motor for these movements. Here, we purify this approximate to 235-kDa protein (p235) from axoplasm and demonstrate that it is a myosin, because it is recognized by a pan-myosin antibody and has an actin-activated Mg-ATPase activity per mg of protein 40-fold higher than that of axoplasm, By low-angle rotary shadowing, p235 differs from myosin II and it does not form bipolar filaments in low salt. The amino acid sequence of a 17-kDa protein that copurifies with p235 shows that it is a squid optic lobe calcium-binding protein, which is more similar by amino acid sequence to calmodulin (69% identity) than to the light chains of myosin II (33% identity). A polyclonal antibody to this light chain was raised bq using a synthetic peptide representing the calcium binding domain least similar to calmodulin. We then cloned this light chain by reverse transcriptase-PCR and showed that this antibody recognizes the bacterially expressed protein but not brain calmodulin. In Western blots of sucrose gradient fractions, the 17-kDa protein is found in the organelle fraction, suggesting that it is a light chain of the p235 myosin that is also associated with organelles. C1 BIOL MARINE LAB,WOODS HOLE,MA 02543. NINCDS,NIH,PEPTIDE SEQUENCING FACIL,NEUROCHEM LAB,BETHESDA,MD 20892. NINCDS,NIH,NEUROBIOL LAB,BETHESDA,MD 20892. RP Bearer, EL (reprint author), BROWN UNIV,DEPT PATHOL & LAB MED,DIV BIOL & MED,BOX G,PROVIDENCE,RI 02912, USA. FU NIGMS NIH HHS [GM47368] NR 37 TC 13 Z9 13 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 JUN 11 PY 1996 VL 93 IS 12 BP 6064 EP 6068 DI 10.1073/pnas.93.12.6064 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500072 PM 8650220 ER PT J AU Schafer, M Mousa, SA Zhang, Q Carter, L Stein, C AF Schafer, M Mousa, SA Zhang, Q Carter, L Stein, C TI Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nociception; pain; neuropeptides; antisense oligonucleotides ID BETA-ENDORPHIN; RECEPTORS; HORMONE; INFLAMMATION; CELLS; ANTINOCICEPTION; MECHANISMS; PROTEIN; INVIVO; STRESS AB Immune cell-derived opioid peptides can activate opioid receptors on peripheral sensory nerves to inhibit inflammatory pain. The intrinsic mechanisms triggering this neuroimmune interaction are unknown, This study investigates the involvement of endogenous corticotropin-releasing factor (CRF) and interleukin-1 beta (IL-1), A specific stress paradigm, cold water swim (CWS), produces potent opioid receptor-specific antinociception in inflamed paws of rats. This effect is dose dependently attenuated by intraplantar but not by intravenous ru-helical CRF, IL-1 receptor antagonist is ineffective, Similarly, local injection of antiserum against CRF, but not to IL-1, dose-dependently reverses this effect, Intravenous anti-CRF is only inhibitory at 10(4)-fold higher concentrations and intravenous CRF does not produce analgesia, Pretreatment of inflamed paws with an 18-mer 3'-3'-end inverted CRF-antisense oligodeoxynucleotide abolishes CWS-induced antinociception. The same treatment significantly reduces the amount of CRF extracted from inflamed paws and the number of CRF-immunostained cells without affecting gross inflammatory signs. A mismatch oligodeoxynucleotide alters neither the CWS effect nor CRF immunoreactivity, These findings identify locally expressed CRF as the predominant agent to trigger opioid release within inflamed tissue, Endogenous IL-1, circulating CRF or antiinflammatory effects, are not involved. Thus, an intact immune system plays an essential role in pain control, which is important for the understanding of pain in immunosuppressed patients with cancer or AIDS. C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. RP Schafer, M (reprint author), NIDA,DIV INTRAMURAL RES,BEHAV PHARMACOL & GENET SECT,NIH,BALTIMORE,MD 21224, USA. OI Stein, Christoph/0000-0001-5240-6836 FU NINDS NIH HHS [R01NS32466] NR 24 TC 107 Z9 111 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 JUN 11 PY 1996 VL 93 IS 12 BP 6096 EP 6100 DI 10.1073/pnas.93.12.6096 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500078 PM 8650225 ER PT J AU Gladyshev, VN Jeang, KT Stadtman, TC AF Gladyshev, VN Jeang, KT Stadtman, TC TI Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE selenium; thioredoxin reductase; TGA; selenocysteine ID PURIFICATION; DEIODINASE; SUBSTRATE; PROTEIN AB The possible relationship of selenium to immunological function which has been suggested for decades was investigated in studies on selenuim metabolism in human T cells, One of the major Se-75-labeled selenoproteins detected was purified to homogeneity and shown to be a homodimer of 55-kDa subunits, Each subunit contained about 1 FAD and at least 0.74 Se. This protein proved to be thioredoxin reductase (TR) on the basis of its catalytic activities, cross-reactivity with anti-rat liver TR antibodies, and sequence identities of several tryptic peptides with the published deduced sequence of human placental TR, Physicochemical characteristics of T-cell TR were similar to those of a selenocysteine (Secys)containing TR recently isolated from human lung adenocarcinoma cells, The sequence of a 12-residue Se-75-labeled tryptic peptide from T-cell TR was identical with a C-terminal-deduced sequence of human placental TR except that Secys was present in the position corresponding to TGA, previously thought to be the termination codon, and this was followed by Gly-499, the actual C-terminal amino acid. The presence of the unusual conserved Cys-Secys-Gly sequence at the C terminus of TR in addition to the redox active cysteines of the Cys-Val-Asn-Val-Gly-Cys motif in the FAD-binding region may account for the peroxidase activity and the relatively low substrate specificity of mammalian TRs, The finding that T-cell TR is a selenoenzyme that contains Se in a conserved C-terminal region provides another example of the role of selenium in a major antioxidant enzyme system (i.e., thioredoxin-thioredoxin reductase), in addition to the well-known glutathione peroxidase enzyme system. C1 NHLBI,BIOCHEM LAB,IR,NATL INST HLTH,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 29 TC 355 Z9 366 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 6146 EP 6151 DI 10.1073/pnas.93.12.6146 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500087 PM 8650234 ER PT J AU Weissman, D Daucher, J Barker, T Adelsberger, J Baseler, M Fauci, AS AF Weissman, D Daucher, J Barker, T Adelsberger, J Baseler, M Fauci, AS TI Cytokine regulation of HIV replication induced by dendritic cell CD4-positive T cell interactions SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED LYMPHADENOPATHY; LYMPH-NODES; HUMAN-LYMPHOCYTES; INFECTED PATIENTS; INTERFERON-GAMMA; HTLV-III/LAV; MACROPHAGES; EXPRESSION; MONOCYTES AB It has been established that human immunodeficiency virus (HIV) replication occurs throughout the course of disease in the lymphoid tissue. We have developed a model system to study the effect of cytokines and other agents on HIV replication using cocultures of DCs and T cells that reflect the cell-to-cell interactions that occur in the microenvironment of lymphoid tissue. Dendritic cells from peripheral blood, when pulsed with small amounts of HIV, induce infection in autologous, unstimulated CD4-positive T cells. Using this system, cytokines, anti-cytokine antibodies, and inhibitors of cellular activation were added to cultures and the effects on cellular proliferation and activation and HIV production were measured. Cytokines that increased T cell proliferation, such as IL-2 and IL-4, enhanced HIV replication, while the effect of IL-12 was more complex, HIV production was inhibited by blocking endogenously produced IL-2, as well as by adding IL-10, which blocks IL-2 secretion, antigen-presenting cell function, and T cell activation. Proinflammatory cytokines induced modest enhancement of viral replication in cocultures of HIV-pulsed DCs and CD4-positive T cells. Thus, using a model of HIV replication that more closely mimics the in vivo microenvironment of lymphoid tissue may allow a better analysis of the effect of cytokines and cytokine networks, as well as agents that modify immune activation on HIV replication. C1 NIH,RES SCHOLARS PROGRAM,HOWARD HUGHES MED INST,BETHESDA,MD 20892. SAIC FREDERICK,FREDERICK,MD 21702. RP Weissman, D (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,10 CTR DR,MSC 1576,BETHESDA,MD 20892, USA. NR 71 TC 29 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN 10 PY 1996 VL 12 IS 9 BP 759 EP 767 DI 10.1089/aid.1996.12.759 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UN834 UT WOS:A1996UN83400003 PM 8738427 ER PT J AU Twerenbold, D Vuilleumier, JL Gerber, D Tadsen, A vandenBrandt, B Gillevet, PM AF Twerenbold, D Vuilleumier, JL Gerber, D Tadsen, A vandenBrandt, B Gillevet, PM TI Detection of single macromolecules using a cryogenic particle detector coupled to a biopolymer mass spectrometer SO APPLIED PHYSICS LETTERS LA English DT Article ID X-RAY-DETECTORS; TUNNELLING JUNCTIONS AB Macromolecules with masses up to 50 kDa have been detected with a cryogenic particle detector in a MALDI time-of-flight biopolymer mass spectrometer. The cryogenic particle detector was a Sn/Sn-ox/Sn tunnel junction operated at a temperature of 0.4 K. A calibration with 6 keV single photons inferred that the delayed detector pulses corresponded to the absorption of the kinetic energy of a single macromolecule. Time-of-flight spectra of lysozyme proteins are presented. The mass resolution is 100 Da at 14 300 Da. The energy sensitive detection mechanism suggests that cryogenic particle detectors have a high and mass independent detection efficiency for macromolecules. (C) 1996 American Institute of Physics. C1 GENSPEC SA,CH-2000 NEUCHATEL,SWITZERLAND. PAUL SCHERRER INST,CH-5232 VILLIGEN,SWITZERLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. GEORGE MASON UNIV,DEPT BIOL,FAIRFAX,VA 22030. RP Twerenbold, D (reprint author), UNIV NEUCHATEL,INST PHYS,RUE AL BREGUET 1,CH-2000 NEUCHATEL,SWITZERLAND. NR 12 TC 81 Z9 82 U1 0 U2 4 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD JUN 10 PY 1996 VL 68 IS 24 BP 3503 EP 3505 DI 10.1063/1.115772 PG 3 WC Physics, Applied SC Physics GA UQ189 UT WOS:A1996UQ18900045 ER PT J AU Thompson, DC Perera, K London, R AF Thompson, DC Perera, K London, R TI Studies on the mechanism of hepatotoxicity of 4-methylphenol (p-cresol): Effects of deuterium labeling and ring substitution SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE p-cresol; quinone methide; deuterium labeling; structure-activity; hepatotoxicity ID PSEUDOMONAS-PUTIDA; METHYLHYDROXYLASE; METABOLISM; TOXICITY AB We recently observed that 4-methylphenol (p-cresol) is toxic to rat liver tissue slices. A possible mechanism involves biotransformation of 4-methylphenol to a reactive quinone methide intermediate which covalently binds to cellular macromolecules and elicits cytotoxicity, In order to obtain further evidence for this proposed mechanism, we studied the effects of deuterium-labeled 4-methylphenol (4-[alpha,alpha,alpha-d(3)]-methylphenol), and the presence of various ring substituents, on the metabolism and toxicity of 4-methylphenol in precision-cut liver slices prepared from male Sprague-Dawley rats. Deuterium-labeled 4-methylphenol was significantly less toxic than the parent compound in rat liver slices (LC(50) = 3.36 vs. 1.31 mM, respectively). In addition, the deuterium-labeled compound was metabolized to a reactive intermediate (measured as glutathione conjugate formation) at a slower rate than that of 4-methylphenol in both liver slices and liver microsomal incubations. The presence of electron withdrawing substituents (2-chloro or 2-bromo) markedly enhanced both metabolism and toxicity, with the exception of 2,6-dibromocresol, which was similar to cresol in terms of rate of metabolism and toxicity. Conversely, the presence of electron donating substituents (2-methoxy, 2-methyl or 2,6-dimethyl) diminished metabolism and toxicity. In addition, methylation of the hydroxyl group to form 4-methylanisole, greatly reduced toxicity. These results support the hypothesis that the toxicity of 4-methylphenol is dependent on the formation of a reactive quinone methide intermediate. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP Thompson, DC (reprint author), TEXAS A&M UNIV,HLTH SCI CTR,COLL MED,DEPT MED PHARMACOL & TOXICOL,COLLEGE STN,TX 77843, USA. FU NIEHS NIH HHS [5 R29 ES06016] NR 20 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUN 10 PY 1996 VL 101 IS 1 BP 1 EP 11 DI 10.1016/0009-2797(96)03707-6 PG 11 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA UV514 UT WOS:A1996UV51400001 PM 8665615 ER PT J AU Adesanya, MR Redman, RS Baum, BJ OConnell, BC AF Adesanya, MR Redman, RS Baum, BJ OConnell, BC TI Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT ADENOVIRUSES; NONHUMAN-PRIMATES; CYSTIC-FIBROSIS; IN-VIVO; EXPRESSION; REPLICATION; LUNG; PATHOGENESIS; SECRETION; PNEUMONIA AB Although replication-deficient adenoviruses can efficiently transfer genes to the salivary glands, the current vectors precipitate an immediate, transient decrease in salivary function. To study the cause of this salivary hypofunction, 10(6)-10(10) plaque-forming units (pfu) of the vector AdCMV beta gal were delivered by retrograde ductal infusion to the submandibular glands (SMGs) of rats. Microscopic analysis of infected glands showed a dose-related, rapidly developing inflammatory response, which at the highest amount of virus was characterized by a predominantly neutrophil-containing infiltrate, focal necrosis, and edema. Moreover, the glands of nude rats developed similar morphologic changes to those of immunocompetent rats. After 3 days, the volume of stimulated saliva secreted from SMGs receiving AdCMV beta gal (6.75 x 10(9) pfu) was similar to 20% that of controls. UV-inactivated virus caused a similar decrease in saliva output. We evaluated to what extent the anti-inflammatory glucocorticoid, dexamethasone, could suppress inflammation and preserve salivary function. Three days after infusion with a high dose of AdCMV beta gal (6.75 x 10(9) pfu), the glands from dexamethasone-treated animals showed markedly less inflammation and no necrosis. Furthermore, there was no significant difference in the average amount of saliva secreted from the infected glands (105 +/- 17 mu l) compared to the control glands (123 +/- 18 Ed). In addition, dexamethasone extended the expression of beta-galactosidase in the SMGs. These results suggest that the adenovirus-mediated acute inflammation in rat SMG is responsible for diminished gland function and transgene expression. Furthermore, we demonstrate a useful role for glucocorticoids in controlling acute inflammation during experimental gene transfer with current adenovirus vectors. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. VET AFFAIRS MED CTR,ORAL PATHOL RES LAB,WASHINGTON,DC 20422. OI O'Connell, Brian/0000-0003-4529-7664 NR 34 TC 107 Z9 107 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 JUN 10 PY 1996 VL 7 IS 9 BP 1085 EP 1093 DI 10.1089/hum.1996.7.9-1085 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD316 UT WOS:A1996WD31600001 PM 8773510 ER PT J AU Aksentijevich, I Pastan, I LunardiIskandar, Y Gallo, RC Gottesman, MM Thierry, AR AF Aksentijevich, I Pastan, I LunardiIskandar, Y Gallo, RC Gottesman, MM Thierry, AR TI In vitro and in vivo liposome-mediated gene transfer leads to human MDR1 expression in mouse bone marrow progenitor cells SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC PRECURSOR CELLS; MULTIDRUG RESISTANCE GENE; P-GLYCOPROTEIN; STEM-CELLS; ADULT MICE; THERAPY; DNA; DELIVERY; TRANSPLANTATION; INTEGRATION AB The ability to select bone marrow cells (BMC) expressing a selectable gene that confers resistance to anticancer drugs would be useful to protect bone marrow during chemotherapy. The human multidrug resistance (MDR1) gene encodes a 170-kD glycoprotein (P-gp), an ATP-dependent transmembrane efflux pump for many different cytotoxic drugs. In this work, we demonstrate efficient expression of the human MDR1 gene in mouse BMC after transfection with a liposomal delivery system (DLS-liposomes). The human MDR1 cDNA expression plasmid (pHaMDR1/A) was encapsulated in DLS-liposonnes and delivered to mouse BMC using two approaches: (i) in vitro transfection of BMC followed by bone marrow transplantation and (ii) in vivo direct systemic gene transfer. After both the in vitro and the in vivo approaches, polymerase chain reaction (PCR) analysis confirmed that the human MDR1 gene was successfully transfected to bone marrow, spleen, and peripheral blood (PB) cells, with the human MDR1 gene detected in BMC for up to 30 days after bone marrow transplantation and 28 days after direct systemic administration. Efflux studies using rhodamine-123 demonstrated function of the MDR1 gene product in the in vitro-transfected BMC. Flow cytometry studies using the human MDR1-specific MRK16 monoclonal antibody confirmed the presence of P-gp in BMC after in vitro transfection, as well as in BMC from reconstituted or in vivo-transfected mice. Transgene expression in both lymphoid and myeloid subpopulations of BMC was demonstrated. Colony-forming units (CFU-Mix) were obtained after exposure of BMC to lethal doses of vincristine, demonstrating functional expression of the MDR1 gene in hematopoietic progenitor cells for up to 1 month. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI thierry, alain/F-9492-2014 NR 36 TC 35 Z9 36 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 JUN 10 PY 1996 VL 7 IS 9 BP 1111 EP 1122 DI 10.1089/hum.1996.7.9-1111 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD316 UT WOS:A1996WD31600004 PM 8773513 ER PT J AU Mullen, CA Snitzer, K Culver, KW Morgan, RA Anderson, WF Blaese, RM AF Mullen, CA Snitzer, K Culver, KW Morgan, RA Anderson, WF Blaese, RM TI Molecular analysis of T lymphocyte-directed gene therapy for adenosine deaminase deficiency: Long-term expression in vivo of genes introduced with a retroviral vector SO HUMAN GENE THERAPY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; MEDIATED TRANSFER; SKIN FIBROBLASTS; RHESUS-MONKEYS; MARROW-CELLS; PATIENT; DISEASE; INVIVO; ADA; SEQUENCE AB Peripheral blood lymphocytes from a patient with adenosine deaminase (ADA) deficiency were transduced in vitro with a replication-defective retroviral vector containing a human ADA-cDNA, Eighteen months after the last of a series of infusions of autologous retroviral vector-treated cells, vector sequences were detectable in DNA isolated from peripheral blood mononuclear cells (PBMCs), with an average copy number approaching one per cell. Increased ADA enzyme activity reaching approximately one-quarter normal levels was found in this population of cells. Other evidence of long-term retroviral vector expression in vivo included neomycin phosphotransferase (NPT) activity and demonstration of persistent vector mRNA by reverse transcriptase polymerase chain reaction (RT-PCR). No evidence of spontaneous reversion of either mutant endogenous ADA allele was found. C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,NORRIS CANC CTR,GENE THERAPY LABS,LOS ANGELES,CA 90033. RP Mullen, CA (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPT PEDIAT,BOX 88,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 32 TC 33 Z9 35 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 JUN 10 PY 1996 VL 7 IS 9 BP 1123 EP 1129 DI 10.1089/hum.1996.7.9-1123 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD316 UT WOS:A1996WD31600005 PM 8773514 ER PT J AU Walker, PS Hengge, UR Udey, MC Aksentijevich, I Vogel, JC AF Walker, PS Hengge, UR Udey, MC Aksentijevich, I Vogel, JC TI Viral interference during simultaneous transduction with two independent helper-free retroviral vectors SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; CELL-LINES; EXPRESSION; THERAPY; LONG AB The ability to stably transduce a single cell with two independent retroviral vectors would have distinct advantages for gene therapy, We determined that cells can be transduced with two distinct retroviral vectors and have quantitated transduction efficiencies in cells infected sequentially and simultaneously, Two amphotropic, helper virus-free, retroviral vectors, a murine Moloney sarcoma virus-based vector containing the nuclear P-galactosidase and neomycin resistance genes (MMSVn beta-gal/neo(R)) and a Harvey virus-derived vector containing the human multidrug resistance gene (HaMDR) were introduced into NIH-3T3 cells, pig keratinocytes, and primary pig fibroblasts simultaneously and sequentially, Analytical flow cytometry was utilized to determine retroviral transduction efficiency by assessing the percentage of cells transduced by either one or both retroviruses, in the absence of selection, Simultaneous retroviral transductions were infrequent events, In addition, transduction of previously infected cells (sequential transductions) occurred at lower than expected frequencies, Our data suggest that there is quantifiable viral interference in sequential retroviral transductions, This interference occurs by a mechanism that appears to be independent of the amphotropic retroviral receptor, Thus, such dual transductions will likely require in vitro selection or the use of a single retrovirus which contains both desired genes on the same genome. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 18 TC 9 Z9 9 U1 0 U2 1 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 JUN 10 PY 1996 VL 7 IS 9 BP 1131 EP 1138 DI 10.1089/hum.1996.7.9-1131 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD316 UT WOS:A1996WD31600006 PM 8773515 ER PT J AU Lynn, RB Hyde, TM Cooperman, RR Miselils, RR AF Lynn, RB Hyde, TM Cooperman, RR Miselils, RR TI Distribution of bombesin-like immunoreactivity in the nucleus of the solitary tract and dorsal motor nucleus of the rat and human: Colocalization with tyrosine hydroxylase SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE vagus; dorsal vagal complex; gastrointestinal; neuropeptide; gastrin releasing peptide ID CENTRAL-NERVOUS-SYSTEM; GASTRIN-RELEASING PEPTIDE; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; BRAIN-STEM PROJECTIONS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CATECHOLAMINE-SYNTHESIZING ENZYMES; IMMUNO-CYTOCHEMICAL LOCALIZATION; NEUROPEPTIDE-Y IMMUNOREACTIVITY; MEDULLA-OBLONGATA; VAGUS NERVE AB Bombesin is a peptide neurotransmitter/neuromodulator with important autonomic and behavioral effects that are mediated, at least in part, by bombesin-containing neurons and nerve terminals in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The distribution of bombesin-like immunoreactive nerve terminals/fibers and cell bodies in relation to a viscerotopically relevant subnuclear map of this region was studied by using an immunoperoxidase technique. In the rat, bombesin fiber/terminal staining was heavy in an area that included the medial subnucleus of the NTS and the DMV over their full rostral-caudal extent. Distinctly void of staining were the gelatinous, central, and rostral commissural subnuclei and the periventricular area of the NTS, regions to which gastric, esophageal, cecal, and colonic primary afferents preferentially project. The caudal commissural and dorsal subnuclei had light bombesin fiber/terminal staining, as did the intermediate, interstitial, ventral, and ventrolateral subnuclei. With colchicine pretreatment, numerous cell bodies were stained in the medial and dorsal subnuclei, with fewer neurons in the caudal commissural. intermediate, interstitial, ventral, and ventrolateral subnuclei. Bombesin-like immunoreactive neurons were found in numerous other areas of the brain, including the ventrolateral medulla, the parabrachial nucleus, and the medial geniculate body. In the human NTS/DMV complex, the distribution of bombesin fiber/terminal staining was very similar to the rat. In addition, occasional bombesin-like immunoreactive neurons were labeled in a number of subnuclei, with clusters of neurons labeled in the dorsal and ventrolateral subnuclei. Double immunofluorescence studies in rat demonstrated that bombesin colocalizes with tyrosine hydroxylase in neurons in the dorsal subnucleus of the NTS. Bombesin does not colocalize with tyrosine hydroxylase in any other location in the brain. In conclusion, the distribution of bombesin in the NTS adheres to a viscerotopically relevant map. This is the anatomical substrate for the effects of bombesin on gastrointestinal function and satiety and its likely role in concluding a meal. The anatomic similarities between human and rat suggest that bombesin has similar functions in the visceral neuraxis of these two species. Bombesin coexists with catecholamines in neurons in the dorsal subnucleus, which likely mediate, in part, the cardiovascular effects of bombesin. (C) 1996 Wiley-Liss, Inc. C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. UNIV PENN,DEPT ANIM BIOL,PHILADELPHIA,PA 19104. UNIV PENN,INST NEUROL SCI,PHILADELPHIA,PA 19104. RP Lynn, RB (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,1025 WALNUT ST,ROOM 901,PHILADELPHIA,PA 19107, USA. FU NIDDK NIH HHS [DK-02094]; NIGMS NIH HHS [GM-27739] NR 148 TC 26 Z9 27 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 10 PY 1996 VL 369 IS 4 BP 552 EP 570 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UN523 UT WOS:A1996UN52300006 PM 8761928 ER PT J AU Tolosa, E Shaw, S AF Tolosa, E Shaw, S TI A fluorogenic assay of endogenous phosphatase for assessment of cell adhesion SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE 3,6-fluorescein diphosphate; cell adhesion; phosphatase; low-shear washing; (method) ID ENDOTHELIAL-CELLS; QUANTITATION AB Assays of cell adhesion generally require prelabeling of cells with radioactive or fluorescent probes. A new fluorogenic phosphatase assay requiring no prelabeling has been developed to quantitate cell number, which can thus serve as the basis for quantitating cell adhesion or migration. The assay uses the non-fluorescent substrate 3,6-fluorescein diphosphate (FDP) whose dephosphorylation generates fluorescein. The fluorescence generated is linear with incubation time and cell number until substrate becomes limiting; the assay easily quantities cells over a range from 10(3) to 10(6) for a variety of cell types, including resting T cells, It is as sensitive as the Cr-51 assay, but has the many advantages of a non-radioactive assay, making more convenient the removal of nonadherent cells by simple 1 x g sedimentation, Unlike most other non-radioactive assays, it requires no pre-incubation; this: (1) reduces cell manipulation; (2) eliminates problems of spontaneous release; and (3) avoids potential dye toxicity. This technique of cell quantitation has been adopted as standard in our laboratory for routine adhesion and migration assays. RP Tolosa, E (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B17,10 CTR DR,MSC 1360,BETHESDA,MD 20892, USA. NR 22 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 10 PY 1996 VL 192 IS 1-2 BP 165 EP 172 DI 10.1016/0022-1759(96)00042-7 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA UU978 UT WOS:A1996UU97800018 PM 8699013 ER PT J AU Carrier, F Bae, I Smith, ML Ayers, DM Fornace, AJ AF Carrier, F Bae, I Smith, ML Ayers, DM Fornace, AJ TI Characterization of the GADD45 response to ionizing radiation in WI-L2-NS cells, a p53 mutant cell line SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Gadd45; WI-L2-NS; p53; ionizing radiation ID DNA-DAMAGING AGENTS; PROTEIN-KINASE-C; GENE; INDUCTION; BINDING; CYCLE; RNA; ACTIVATION AB We have previously reported that WI-L2-NS, a human lymphoblastoid cell line, has very high basal levels of GADD45 mRNA and protein in spite of a p53 mutation at amino acid 237. Regardless of the amount of Gadd45 in this cell line, no growth suppression activity was detected. We report here that in WI-L2-NS, the mutated p53 protein adopts predominantly a wild type (wt) conformation and binds to the p53 binding site in the GADD45 third intron. In this cell line, the already high levels of mutated p53 protein can be induced further by ionizing radiation (IR) but the response of the p53 downstream effector genes is altered. Induction of GADD45 and CIP1/WAF1 is reduced compared to p53 wt cell lines but is still substantially higher than the average fold induction obtained from 39 p53 mutant cell lines. Induction of the MDM2 gene was not detected in WI-L2-NS following IR. The induction pattern of the three p53 effector genes by the alkylating agent methylmethane sulfonate (MMS) was also attenuated in WI-L2-NS cells. In TK6 cells, a WI-L2-NS sister cell line having a p53 wt genotype, the induction of the p53 downstream effecters is normal, i.e. induced, both at the protein and the mRNA levels. These results indicate that the DNA binding activity of the mutated p53 protein in WI-L2-NS might be responsible, at least in part, for the high basal levels of GADD45 but can not mediate the full induction of the p53 downstream effector genes. The reason(s) for-the inability of Gadd45 to suppress growth in this cell line remains however unknown. RP Carrier, F (reprint author), NCI,MOLEC PHARMACOL LAB,DTP,DCT,BLDG 37,ROOM 5C09,BETHESDA,MD 20892, USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; Ayers, Donald/0000-0003-2668-8408 NR 25 TC 19 Z9 19 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 JUN 10 PY 1996 VL 352 IS 1-2 BP 79 EP 86 DI 10.1016/0027-5107(95)00255-3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA UU370 UT WOS:A1996UU37000012 PM 8676920 ER PT J AU Ashby, J Waters, MD Preston, J Adler, ID Douglas, GR Fielder, R Shelby, MD Anderson, D Sofuni, T Gopalan, HNB Becking, G SonichMullin, C AF Ashby, J Waters, MD Preston, J Adler, ID Douglas, GR Fielder, R Shelby, MD Anderson, D Sofuni, T Gopalan, HNB Becking, G SonichMullin, C TI Current issues in mutagenesis and carcinogenesis .67. IPCS harmonization of methods for the prediction and quantification of human carcinogenic/mutagenic hazard, and for indicating the probable mechanism of action of carcinogens SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article AB A flow chart is presented as a recommended sequence of tests to predict the carcinogenic hazard, and to predict and quantify the mutagenic hazard to germ cells of chemicals to humans. Ten associated principles of testing for these endpoints are also suggested. These recommendations are the result of a meeting convened under the auspices of the International Programme on Chemical Safety (IPCS), as part of their project on 'Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals'. The meeting was held at Carshalton, Surrey, from 13-17 February 1995. C1 ZENECA CTL,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. US EPA,NHEERL,RES TRIANGLE PK,NC 27711. CIIT,RES TRIANGLE PK,NC 27709. GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT GMBH,D-85758 OBERSCHLEISSHEIM,GERMANY. CTR ENVIRONM HLTH,OTTAWA,ON K1A 0L2,CANADA. DEPT HLTH,DIV HEF,LONDON SE1 6LW,ENGLAND. NIEHS,RES TRIANGLE PK,NC 27709. BIBRA INT,CARSHALTON SM5 4DS,SURREY,ENGLAND. NATL INST HLTH SCI,BIOL SAFETY RES CTR,DIV GENET & MUTAGENESIS,SETAGAYA KU,TOKYO 158,JAPAN. UNEP,NAIROBI,KENYA. WHO,PCS,IRRU,RES TRIANGLE PK,NC 27709. WHO,PCS,ARM,CH-1211 GENEVA,SWITZERLAND. NR 0 TC 38 Z9 38 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 JUN 10 PY 1996 VL 352 IS 1-2 BP 153 EP 157 DI 10.1016/0027-5107(95)00221-9 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA UU370 UT WOS:A1996UU37000020 PM 8676904 ER PT J AU Shelby, MD AF Shelby, MD TI Current series in mutagenesis and carcinogenesis .68. Selecting chemicals and assays for assessing mammalian germ cell mutagenicity SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE mutagen; test scheme; genetic risk; dominant lethal test; heritable translocation test; specific locus test ID MICE; MOUSE RP Shelby, MD (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 15 TC 39 Z9 42 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 JUN 10 PY 1996 VL 352 IS 1-2 BP 159 EP 167 DI 10.1016/0027-5107(95)00222-7 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA UU370 UT WOS:A1996UU37000021 PM 8676905 ER PT J AU Ravichandran, V Chawla, A Roche, PA AF Ravichandran, V Chawla, A Roche, PA TI Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNAPTOSOMAL-ASSOCIATED PROTEIN; RECEPTORS; TRANSPORT; SUBSTRATE; FUSION AB The specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed syntaxin. These proteins, together with SNAP-25 (synaptosome associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery, Synaptobrevin/VAMP and syntaxin are ubiquitously expressed proteins and are believed to be involved in vesicular transport in mast (if not all) cells. However, SNAP-25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP-25 exists to facilitate transport vesicle/target membrane fusion in other tissues, Using the yeast two-hybrid system, we have identified a 23-kDa protein from human B lymphocytes (termed SNAP-23) that binds tightly to multiple syntaxins and synaptobrevins/VAMPs in vitro. SNAP-23 is 59% identical with SNAP-25. Unlike SNAP-25, SNAP-23 was expressed in all tissues examined, These findings suggest that SNAP-23 is an essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion in all mammalian cells. C1 NIH,NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 27 TC 247 Z9 250 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 JUN 7 PY 1996 VL 271 IS 23 BP 13300 EP 13303 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP385 UT WOS:A1996UP38500003 PM 8663154 ER PT J AU Guimaraes, MJ Bazan, JF Castagnola, J Diaz, S Copeland, NG Gilbert, DJ Jenkins, NA Varki, A Zlotnik, A AF Guimaraes, MJ Bazan, JF Castagnola, J Diaz, S Copeland, NG Gilbert, DJ Jenkins, NA Varki, A Zlotnik, A TI Molecular cloning and characterization of lysosomal sialic acid O-acetylesterase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DE-ORTHO-ACETYLATION; INFLUENZA-C VIRUS; COLONY-STIMULATING FACTOR; RAT-LIVER; CELL; GROWTH; IDENTIFICATION; PROLIFERATION; PURIFICATION; LYMPHOCYTES AB O-Acetylation and de-O-acetylation of sialic acids have been implicated in the regulation of a variety of biological phenomena, including endogenous lectin recognition, tumor antigenicity, virus binding, and complement activation. Applying a strategy designed to identify genes preferentially expressed in active sites of embryonic hematopoiesis, we isolated a novel cDNA from the pluripotent hematopoietic cell line FDCP-mixA4 whose open reading frame contained sequences homologous to peptide fragments of a lysosomal sialic acid O-acetylesterase (Use) previously purified from rat liver, but with no evident similarity to endoplasmic reticulum-derived acetylesterases. The expressed Lse protein exhibits sialic-acid O-acetylesterase activity that is not attributable to a typical serine esterase active site, Lse expression is spatially and temporally restricted during embryogenesis, and its mRNA levels correlate with differences in O-acetylesterase activity described in adult tissues and blood cell. types, Using interspecific backcross analysis, we further mapped the Ise gene to the central region of mouse chromosome 9, This constitutes the first report on the molecular cloning of a sialic acid specific O-acetylesterase in vertebrates and suggests novel roles for the 9-O-acetyl modification of sialic acids during the development and differentiation of mammalian organisms. C1 UNIV CALIF SAN DIEGO,CTR CANC,GLYCOBIOL PROGRAM,LA JOLLA,CA 92093. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP Guimaraes, MJ (reprint author), DNAX RES INST MOLEC & CELLULAR BIOL INC,901 CALIF AVE,PALO ALTO,CA 94304, USA. RI Bazan, J. Fernando/B-4562-2010; Zlotnik, Albert/C-3791-2011 FU NCI NIH HHS [N01-CO-4600]; NIGMS NIH HHS [R01GM32373] NR 63 TC 20 Z9 22 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 JUN 7 PY 1996 VL 271 IS 23 BP 13697 EP 13705 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP385 UT WOS:A1996UP38500061 PM 8662838 ER PT J AU Hsu, DKW Guo, Y Alberts, GF Copeland, NG Gilbert, DJ Jenkins, NA Peifley, KA Winkles, JA AF Hsu, DKW Guo, Y Alberts, GF Copeland, NG Gilbert, DJ Jenkins, NA Peifley, KA Winkles, JA TI Identification of a murine TEF-1-related gene expressed after mitogenic stimulation of quiescent fibroblasts and during myogenic differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE PROGRESSION; GROWTH FACTOR-I; ENHANCER FACTOR-I; INTIMAL HYPERPLASIA; HEPARIN-BINDING; POINT MUTATION; SINGLE GENE; RECEPTOR; TRANSCRIPTION; CLONING AB Fibroblast growth factor (FGF)-1 binding to cell surface receptors stimulates an intracellular signaling pathway that ultimately promotes the transcriptional activation of specific genes. We have used a mRNA differential display method to identify FGF-1-inducible genes in mouse NIH 3T3 fibroblasts. Here, we report that one of these genes, FGF-regulated (FR)-19, is predicted to encode a member of the transcriptional enhancer factor (TEF)-1 family of structurally related DNA-binding proteins. Specifically, the deduced FR-19 amino acid sequence has similar to 89, 77, and 68% overall identity to chicken TEF-1A, mouse TEF-1, and mouse embryonic TEA domain-containing factor, respectively. Gel mobility shift experiments indicate that FR-19, like TEF-1, and bind the GT-IIC motif found in the SV40 enhancer. The FR-19 gene maps in the distal region of mouse chromosome 6, and analysis of several FR-19 cDNA clones indicates that at least two FR-19 isoforms may be expressed from this locus. FGF-1 induction of FR-19 mRNA expression in mouse fibroblasts is first detectable at 4 h after FGF-1 addition and is dependent on de novo RNA and protein synthesis. FGF-2, calf serum, platelet-derived growth factor-BB, and phorbol 12-myristate 13-acetate can also induce FR-19 mRNA levels. We have also found that FR-19 mRNA expression increases during mouse C2C12 myoblast differentiation in vitro. The FR-19 gene is expressed in vivo in a tissue-specific manner, with a relatively high level detected in lung. These results indicate that increased expression of a TEF-1-related protein may be important for both mitogen-simulated fibroblast proliferation and skeletal muscle cell differentiation. C1 AMER RED CROSS, DEPT BIOL MOLEC, HOLLAND LAB, ROCKVILLE, MD 20855 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. GEORGE WASHINGTON UNIV, MED CTR, DEPT BIOCHEM & MOLEC BIOL, WASHINGTON, DC 20037 USA. FU NHLBI NIH HHS [HL-07698, HL-39727] NR 70 TC 33 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 7 PY 1996 VL 271 IS 23 BP 13786 EP 13795 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP385 UT WOS:A1996UP38500073 PM 8662936 ER PT J AU Oda, N Saxena, JK Jenkins, TM Prasad, R Wilson, SH Ackerman, EJ AF Oda, N Saxena, JK Jenkins, TM Prasad, R Wilson, SH Ackerman, EJ TI DNA polymerases alpha and beta are required for DNA repair in an efficient nuclear extract from Xenopus oocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXCISION REPAIR; MAMMALIAN-CELLS; DELTA; COMPLEMENTATION; PHOTOPRODUCTS; SEQUENCES; EPSILON; DIMERS AB Xenopus oocytes and an oocyte nuclear extract efficiently repair the bulky DNA lesions cyclobutane pyrimidine dimers, (6-4) photoproducts, and N-acetoxy-2-aminofluorene (AAF) adducts by san excision repair mechanism. Nearly all (>95%) of the input damaged DNA was repaired within 5 h in both infected cells and extracts with no significant incorporation of label into control undamaged DNA. Remarkably, more than 10(10) cyclobutane pyrimidine dimers or (6-4) photoproducts are repaired/nuclei. The extracts are free from nuclease activity, and repair is independent of exogenous light. Both the high efficiency and DNA polymerase requirements of this system appear to be different from extracts derived from human cells. We demonstrated a requirement for DNA polymerases alpha and beta in repair of both photoproducts and AAF by inhibiting repair with several independent antibodies specific to either DNA polymerases alpha or beta and then restoring repair by adding the appropriate purified polymerase. Repair is inhibited by aphidicolin at concentrations specific for blocking DNA polymerase alpha and dideoxynucleotide triphosphates at concentrations specific for inhibiting DNA polymerase beta. C1 NIDDK, NIH, OFF SCI DIRECTOR, BETHESDA, MD 20892 USA. UNIV TEXAS, MED BRANCH, SCALY CTR MOL SCI, GALVESTON, TX 77555 USA. NR 38 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 7 PY 1996 VL 271 IS 23 BP 13816 EP 13820 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP385 UT WOS:A1996UP38500077 PM 8662731 ER PT J AU Olsson, NU Harding, AJ Harper, C Salem, N AF Olsson, NU Harding, AJ Harper, C Salem, N TI High-performance liquid chromatography method with lightscattering detection for measurements of lipid class composition: Analysis of brains from alcoholics SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article DE lipids; cholesterol; sulfatides; phospholipids; sphingolipids ID FATTY-ACID COMPOSITION; SEPARATION; ETHANOL AB A high-performance liquid chromatographic method with evaporative light-scattering detection was developed for the analysis of intact lipid classes in nervous tissue. The method had the ability to resolve plasmalogen-phosphatidyl-ethanolamine and diacyl-phosphatidylethanolamine along with other major phospholipid classes in a single run. This technique was employed for the investigation of the effects of chronic alcohol consumption on the membrane lipid class composition of human brains (alcoholics, n=13; controls, n=11). Measurements were performed on cholesterol, cerebrosides, sulfatides, phospholipids and sphingolipids in total lipid extracts of white matter, gray matter and cerebellar regions of human brains. No significant differences in the lipid class composition between the groups were observed. C1 NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,NIH,ROCKVILLE,MD 20852. UNIV SYDNEY,DEPT PATHOL,NEUROPATHOL UNIT,SYDNEY,NSW 2006,AUSTRALIA. FU NIAAA NIH HHS [AA09272] NR 33 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUN 7 PY 1996 VL 681 IS 2 BP 213 EP 218 DI 10.1016/0378-4347(95)00576-5 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UT918 UT WOS:A1996UT91800001 PM 8811429 ER PT J AU Karton, Y Jiang, JL Ji, XD Melman, N Olah, ME Stiles, GL Jacobson, KA AF Karton, Y Jiang, JL Ji, XD Melman, N Olah, ME Stiles, GL Jacobson, KA TI Synthesis and biological activities of flavonoid derivatives as A3 adenosine receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; RAT-BRAIN; INHIBITION AB A broad screening of phytochemicals has demonstrated that certain flavone and flavonol derivatives have a relatively high affinity at A(3) adenosine receptors, with K-i values of greater than or equal to 1 mu M (Ji et al. J. Meld. Chem. 1996, 39, 781-788). We have further modified the flavone structure to achieve a degree of selectivity for cloned human brain A(3) receptors, determined in competitive binding assays versus [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)adenosine-5 amide)l. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-N-6-PIA ([H-3]-(R)-N-6-phenylisopropyladenosine and [H-3]CGS21680 [[H-3]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)adenosine], respectively. The triethyl and tripropyl ether derivatives of the flavonol galangin, 4, had K-i values of 0.3-0.4 mu M at human A(3) receptors. The presence of a 5-hydroxyl group increased selectivity of flavonols for human A(3) receptors. The 2',3,4',7-tetraethyl ether derivative of the flavonol morin, 7, displayed a K-i value of 8.8 mu M at human A(3) receptors and was inactive at rat A(1)/A(2A) receptors. 3,6-Dichloro-2'-(isopropyloxy)-4'-methylflavone, 11e, was both potent and highly selective (similar to 200 fold) for human A(3) receptors (K-i 0.56 mu M). Among dihydroflavonol analogues, the 2-styryl instead of the 2-aryl substituent, in 15, afforded selectivity for human A(3) VS rat A(1) or A(2A) receptors. The 2-styryl-6-propoxy derivative, 20, of the furanochromone visnagin was 30-fold selective for human A(3) receptors vs either rat A(1) or A(2A) receptors. Several of the more potent derivatives effectively antagonized the effects of an agonist in a functional A(3) receptor assay, i.e. inhibition of adenylyl cyclase in CHO cells expressing cloned rat A(3) receptors. In conclusion, these series of flavonoids provide leads for the development of novel potent and subtype selective A(3) antagonists. C1 NIDDK,MOL RECOGNIT SECT,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 49 TC 94 Z9 95 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 7 PY 1996 VL 39 IS 12 BP 2293 EP 2301 DI 10.1021/jm950923i PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UQ016 UT WOS:A1996UQ01600003 PM 8691424 ER PT J AU Eastin, WC Elwell, MR Grumbein, S Yuan, JH AF Eastin, WC Elwell, MR Grumbein, S Yuan, JH TI Effects of D&C yellow no 11 ingestion on F344/N rats and B6C3F(1) mice SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article AB D&C yellow no. 11 (CAS no. 8003-22-3) was administered in the feed at concentrations of 500-50,000 ppm to groups of F344/N rats and B6C3F, mice of each sex for 13 wk to determine the toxicity. In addition, a perinatal study was conducted to determine the effects of feeding diets containing D&C yellow no. I I to female rats during reproduction and to their offspring. Although the estimated intake (g/kg) of D&C yellow no. 11 of mice was more than twice that of rats, the results were generally similar for both rats and mice. In both species, D&C yellow no. 11 caused no mortality, but it did reduce body weight gain slightly in both sexes of rats exposed to 17,000 and 50,000 ppm. Absolute and relative liver weights were significantly increased in all groups of rats and mice administered D&C yellow no. 11 in the feed. There was minimal to mild degeneration of the periportal hepatocytes in rats at doses of 1700 ppm and higher and in mice at 5000 ppm and above. A dose-related yellow-brown pigment was observed in hepatocytes, Kupffer cells, and biliary epithelium of the liver of both sexes of both species and in the renal tubule epithelium in both sexes oi rats. In male rats, all treated groups had increased number and size of hyaline droplets in the renal tubule epithelium of the cortex and outer medulla. To determine if these renal and hepatic lesions were reversible, male rats were administered 5000 ppm dietary D&C yellow no. 11 for 70 d and then examined at 3, 14, and 28 d alter the chemical was removed from the diet. Pigment persisted in the kidney and liver for as long as 28 d following removal of D&C yellow no. 11 from the diet, but hepatocellular degeneration and cytoplasmic alteration in the kidney completely resolved by d 3 and 14, respectively. In the perinatal toxicity study, body weight gain in rat dams given diets containing as much as 50,000 ppm D&C yellow no. 11 for 4 wk before mating to untreated males was similar to that oi controls at the time of mating but was lower at parturition and weaning. However, fertility gestation length, litter size, and pup birth weights were unaffected by treatment. At weaning there was a significant dose-related decrease in pup body weights from the 5000, 17,000 and 50,000 ppm groups. At 8 wk of age, pups fed the same dosed-feed concentrations as the dams had depressed body weights in the 17,000 and 50,000 ppm treated groups. Microscopic lesions in the liver and kidney of the pups in all dose groups were similar to those described in the 13-wk study. The results of these studies indicate that compound-related effects occurred at all dietary concentrations of D&C yellow no. 11. Liver weights were increased in dosed rats and mice, minimal to mild hepatocellular degeneration was seen in rats receiving dietary concentrations of 1700 ppm and above and in mice 5000 ppm and above, and there was an increase in the number and size of hyaline droplets in all dosed groups of male rats. Similar compound-related effects were also seen in all dosed rats in the perinatal toxicity study. With the exception of pigment accumulation, the treatment-related kidney and liver lesions in male rats were reversible by 14 d after chemical was withdrawn from the diet. C1 PATHOL ASSOCIATES INC,FREDERICK,MD. RP Eastin, WC (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JUN 7 PY 1996 VL 48 IS 2 BP 197 EP 213 DI 10.1080/009841096161438 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UQ875 UT WOS:A1996UQ87500008 PM 8642626 ER PT J AU Price, SR Nightingale, MS Tsuchiya, M Moss, J Vaughan, M AF Price, SR Nightingale, MS Tsuchiya, M Moss, J Vaughan, M TI Interspecies relationships among ADP-ribosylation factors (ARFs): Evidence of evolutionary pressure to maintain individual identities SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE guanine nucleotide-binding proteins; evolution; phylogeny; structure-function ID NUCLEOTIDE-BINDING-PROTEINS; CHOLERA-TOXIN; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; SELECTIVE AMPLIFICATION; REGULATORY COMPONENT; ADENYLATE-CYCLASE; BOVINE BRAIN; GTP; EXPRESSION AB ADP-ribosylation factors (ARFs) are similar to 20-kDa guanine nucleotide-binding proteins that are allosteric activators of the NAD:arginine ADP-ribosyltransferase activity of cholera toxin and appear to play a role in intracellular vesicular trafficking. Although the physiological roles of these proteins have not been defined, it has been presumed that each has a specific intracellular function. To obtain genetic evidence that each ARF is under evolutionary pressure to maintain its structure, and presumably function, rat ARF cDNA clones were isolated and their nucleotide and deduced amino acid sequences were compared to those of other mammalian ARFs, Deduced amino acid sequences for rat ARFs 1, 2, 3, 5 and 6 were identical to those of the known cognate human and bovine ARFs; rat ARF4 was 96% identical to human ARF4, Nucleotide sequences of both the untranslated as well as the coding regions were highly conserved. These results indicate that the ARF proteins are, as a family, extraordinarily well conserved across mammalian species. The unusually high degree of conservation of the untranslated regions is consistent with these regions having important regulatory roles and that individual ARFs contain structurally unique elements required for specific functions. C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NR 50 TC 8 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUN 7 PY 1996 VL 159 IS 1 BP 15 EP 23 PG 9 WC Cell Biology SC Cell Biology GA UV967 UT WOS:A1996UV96700003 PM 8813705 ER PT J AU Fuchs, EJ Ridge, JP Matzinger, P AF Fuchs, EJ Ridge, JP Matzinger, P TI Immunological tolerance - Reply SO SCIENCE LA English DT Letter C1 NIAID,SECT T CELL TOLERANCE & MEMORY,GHOST LAB,NIH,BETHESDA,MD 20892. NR 13 TC 5 Z9 5 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 7 PY 1996 VL 272 IS 5267 BP 1406 EP 1408 DI 10.1126/science.272.5267.1406 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UP899 UT WOS:A1996UP89900004 PM 17770866 ER PT J AU Simons, SS AF Simons, SS TI Environmental estrogens: Can two ''alrights'' make a wrong? SO SCIENCE LA English DT Editorial Material ID HORMONE-BINDING; RECEPTOR RP Simons, SS (reprint author), NIDDKD,STEROID HORMONES SECT,NIH,ROOM B2A-07,BLDG 8,BETHESDA,MD 20892, USA. NR 14 TC 26 Z9 26 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 7 PY 1996 VL 272 IS 5267 BP 1451 EP 1451 DI 10.1126/science.272.5267.1451 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UP899 UT WOS:A1996UP89900037 PM 8633235 ER PT J AU Alter, HJ AF Alter, HJ TI The cloning and clinical implications of HGV and HGBV-C SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NON-A; HEPATITIS RP Alter, HJ (reprint author), NIH,BETHESDA,MD 20892, USA. NR 8 TC 237 Z9 242 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 1996 VL 334 IS 23 BP 1536 EP 1537 DI 10.1056/NEJM199606063342310 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UN799 UT WOS:A1996UN79900010 PM 8618611 ER PT J AU Rojas, JM Coque, JJR Guerrero, C Aroca, P deMora, JF delaCruz, X Lorenzi, MV Esteban, LM Santos, E AF Rojas, JM Coque, JJR Guerrero, C Aroca, P deMora, JF delaCruz, X Lorenzi, MV Esteban, LM Santos, E TI A 15 amino acid stretch close to the Grb2-binding domain defines two differentially expressed hSos1 isoforms with markedly different Grb2 binding affinity and biological activity SO ONCOGENE LA English DT Article DE hSos1; isoforms; Ras activation; Grb2 binding; differential expression ID RECEPTOR TYROSINE KINASES; GUANINE-NUCLEOTIDE EXCHANGE; GROWTH-FACTOR RECEPTORS; SIGNAL TRANSDUCTION; SEVENLESS GENE; SH3 DOMAINS; RAS; PROTEIN; CELLS; IDENTIFICATION AB We compared structure, expression and functional properties of two hSos1 cDNA isoforms (IsfI and Isf II) isolated, respectively, from human fetal brain and adult skeletal muscle libraries, IsfI and IsfII nucleotide sequences differ only by the presence in IsfII of an in-frame 45 bp insertion located near the first proline-rich motif required for Grb2 binding, Some human tissues express only one isoform whereas others express different proportions of both in fetal and adult stages, In vitro binding assays and in vivo functional studies showed that IsfII exhibits significantly higher Grb2 binding affinity and biological activity than IsfI, These results suggest that functionally different hSos1 isoforms, with differential tissue expression and distribution, play important regulatory roles in the mechanisms controlling Ras activation in different tissues and/or developmental stages. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Font de Mora, Jaime/H-6304-2015; Guerrero, Carmen/F-1776-2010; OI Font de Mora, Jaime/0000-0002-6816-2095; Guerrero, Carmen/0000-0002-8747-6831; De la Cruz Montserrat, Fco. Xavier/0000-0002-9738-8472 NR 58 TC 10 Z9 11 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 6 PY 1996 VL 12 IS 11 BP 2291 EP 2300 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UQ220 UT WOS:A1996UQ22000005 PM 8649768 ER PT J AU Seyfert, VL Allman, D He, YS Staudt, LM AF Seyfert, VL Allman, D He, YS Staudt, LM TI Transcriptional repression by the proto-oncogene BCL-6 SO ONCOGENE LA English DT Article DE BCL-6; repression; lymphoma; POZ domain ID GERMINAL-CENTERS; CONSERVED DOMAIN; GENE; DROSOPHILA; PROTEINS; IDENTIFICATION; TRANSLOCATIONS; EXPRESSION; ACTIVATORS; LYMPHOMAS AB In up to 45% of reported cases of the non-Hodgkin's lymphoma, diffuse large cell lymphoma, there are translocations of the BCL-6 gene, which are presumed to deregulate its expression, The BCL-6 protein, which is unmutated in these lymphomas, contains six Kruppel-like zinc fingers at its carboxy terminus and a 121 amino acid domain at its amino terminus, termed the POZ domain, which bears homology with amino terminal domains in a subset zinc finger transcription factors, In this study, we tested whether BCL-6 regulates transcription and if the POZ domain has a role in this function. The BCL-6 POZ domain, when fused to the GAL4 DNA binding domain, strongly repressed transcriptional activation initiated from several different promoters including the SV40 enhancer/promoter. Repression was also observed when the fusion protein was bound at a distance of 200 bp 5' of the promoter, When the GAL4/BCL6 POZ domain fusion protein was expressed in yeast, it was able to homodimerize in the nucleus, Nevertheless, in contrast with mammalian cells, the fusion protein did not repress transcription, To test the ability of the full length BCl-6 protein to repress transcription when bound to DNA through its zinc finger DNA binding domain, high affinity BCL-6 binding sites were selected from a pool of random oligonucleotides. Full length BCL-6 was able to strongly repress transcription when bound to its cognate site cloned upstream of the thymidine kinase promoter, This repression was mediated, in large measure, by the POZ domain, although a variant of BCL-6 lacking the POZ domain was able to repress transcription modestly, The ability of BCL-6 to function as a transcriptional repressor may contribute to its ability to transform B lymphocytes in diffuse large cell lymphoma. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NR 47 TC 183 Z9 184 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 6 PY 1996 VL 12 IS 11 BP 2331 EP 2342 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UQ220 UT WOS:A1996UQ22000010 PM 8649773 ER PT J AU Jakus, J Yeudall, WA AF Jakus, J Yeudall, WA TI Growth inhibitory concentrations of EGF induce p21 (WAF1/Cip1) and alter cell cycle control in squamous carcinoma cells SO ONCOGENE LA English DT Article DE epidermal growth factor; p21; WAF1; Cip1; PCNA; cyclin dependent kinase ID HUMAN EPIDERMOID CARCINOMA; DEPENDENT KINASES; A431 CELLS; RECEPTOR; CULTURE; PROTEIN; HEAD; NECK; DIFFERENTIATION; OVEREXPRESSION AB Previous studies have reported inhibition of A431 squamous carcinoma cell growth by nanomolar concentrations of epidermal growth factor (EGF), a potent mitogen for cells of epithelial origin, In this study, we examined potential mechanisms through which inhibition of keratinocyte growth mediated by EGF might occur by analysing components of the cell cycle regulatory machinery in A431, HN6 and HN30 keratinocytes in the presence of growth inhibitory or growth stimulatory doses of EGF, Treatment of cells with 25 pM EGF produced an increase in [H-3]thymidine incorporation in A431, HN6 and HN30 cells, with respect to control cultures, Exposure to 2.5 nM EGF reduced [H-3]thymidine incorporation in A431 cells and HN6 cells to 11% and 70% of control levels, respectively, whereas HN30 cells continued to proliferate in the presence of EGF, [H-3]thymidine incorporation assays carried out over 24 h revealed repression of DNA synthesis in A431 cells after 12 h exposure to 2.5 nM EGF compared to untreated cells, Flow cytometry studies demonstrated accumulation of cells in G(0)/G(1) after addition of 2.5 nM, but not 25 pM EGF, Western blot analysis revealed elevation of p21 (WAF1/CIP1/SDI1) protein levels in A431 and HN6 cells under growth-inhibitory conditions, Stimulatory doses of EGF did not induce p21 in these cells, Northern blot hybridization demonstrated elevated levels of p21 mRNA within 4 h of exposure of A431 cells to 2.5 nM EGF, which remained elevated above basal levels at 24 h, In vitro kinase assays demonstrated temporal differences in CDK2, and CDK6 activities which were related to EGF concentration, Immunocomplex Western blotting demonstrated increased association of p21 with CDK2 and CDK6 in A431 cells treated with 2.5 nM EGF, Furthermore, temporal alterations in the association of PCNA with p21 and with CDK6 were observed, The data indicate that p21 is a likely mediator of EGF-induced growth-inhibition, probably through mechanisms involving sequestration of PCNA and inhibition of CDK activity. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC CARCINOGENESIS GRP,BETHESDA,MD 20892. NR 42 TC 80 Z9 81 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 6 PY 1996 VL 12 IS 11 BP 2369 EP 2376 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UQ220 UT WOS:A1996UQ22000014 PM 8649777 ER PT J AU Lehel, C Olah, Z Petrovics, G Jakab, G Anderson, WB AF Lehel, C Olah, Z Petrovics, G Jakab, G Anderson, WB TI Influence of various domains of protein kinase C epsilon on its PMA-induced translocation from the Golgi to the plasma membrane SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BREFELDIN-A; ORGANELLE STRUCTURE; MONENSIN; COMPLEX; MECHANISM; CISTERNAE AB Subcellular redistribution (translocation) was initiated by treatment of NIH 3T3 cells overexpressing different epitope-tagged fragments of PKC epsilon with PMA, and was analyzed by immunocytochemistry. The PMA-induced translocation of hole PKC epsilon, as well as fragments epsilon 2 (zinc finger domain + pseudosubstrate domain) and epsilon 7 (zinc finger domain + hinge region) from the Golgi to the plasma membrane was rapid (<10 min), while translocation of fragment epsilon 3 (zinc finger domain) was much slower (30-60 min). These results, combined with results of studies carried out at 20 degrees C to inhibit exocytotic vesicle traffic, indicated that PMA-induced translocation from the Golgi to the plasma membrane may proceed by two distinct mechanisms: a rapid, vesicle independent process noted with hole PKC epsilon (which requires the presence of the pseudosubstrate and/or hinge regions), and a slow, vesicle-dependent pathway observed with the zinc finger fragment. (C) 1996 Academic Press, Inc. C1 NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. NR 20 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 5 PY 1996 VL 223 IS 1 BP 98 EP 103 DI 10.1006/bbrc.1996.0852 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UQ946 UT WOS:A1996UQ94600017 PM 8660386 ER PT J AU Trimble, L Perales, MA Knazek, R Lieberman, J AF Trimble, L Perales, MA Knazek, R Lieberman, J TI Serum enhances the ex vivo generation of HIV-specific cytotoxic T cells SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE HIV; cytotoxic T lymphocytes (CTL); serum ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; IMMUNOTHERAPY; INFECTION; EXPANSION; GENE; AIDS; LUNG AB The ex vivo expansion of antigen-specific cytotoxic T lymphocyte (CTL) lines is being developed for immunotherapy of viral infections and cancer and is critically dependent on the precise cell expansion and stimulation conditions. In this article, we investigate medium requirements for the development of HIV-specific CTL in cell lines generated from the peripheral blood of seven asymptomatic HIV-infected individuals. We find that HIV specific CTL do not readily develop in the serum-free medium AIM V but do develop if the medium is supplemented with 1% plasma or serum. T cell lines with antigen-specific cytolytic activity express more cell-surface CD57 than do cell lines grown in the absence of serum or plasma. Three sources of serum (human autologous, human AB, or fetal calf) are comparable. Human plasma is somewhat less effective than serum from an identical source. (C) 1996 John Wiley & Sons, Inc. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. RI Lieberman, Judy/A-2717-2015 NR 24 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 5 PY 1996 VL 50 IS 5 BP 521 EP 528 DI 10.1002/(SICI)1097-0290(19960605)50:5<521::AID-BIT6>3.0.CO;2-H PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UH438 UT WOS:A1996UH43800007 PM 18627014 ER PT J AU Grant, BF Hasin, DS Dawson, DA AF Grant, BF Hasin, DS Dawson, DA TI The relationship between DSM-IV alcohol use disorders and DSM-IV major depression: Examination of the primary secondary distinction in a general population sample SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE primary-secondary distinction; alcohol use disorder; major depression; familial aggregation; comorbidity; primary depression; secondary depression ID DIAGNOSTIC CRITERIA; FAMILY HISTORY; FOLLOW-UP; UNIPOLAR AB This study examined the primary-secondary distinction with respect to DSM-IV alcohol use disorders and major depression in a large representative sample of the USA. Primary, secondary and concurrent depressives (i.e. the comorbid groups), respondents classified with major depression only and respondents classified with alcohol use disorders only were compared on a large number of sociodemographic, alcohol-related, depression-related and drug-related variables, Results were at variance with a majority of findings from the treatment literature with regard to familial aggregation of alcohol use disorders and sociodemographic, alcohol and depression profiles. Implications of the results are discussed in terms of the diagnostic and prognostic significance of the primary-secondary distinction. C1 COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,MSC 7003,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 40 TC 51 Z9 53 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN 5 PY 1996 VL 38 IS 2-3 BP 113 EP 128 DI 10.1016/0165-0327(96)00002-X PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UR699 UT WOS:A1996UR69900005 PM 8791180 ER PT J AU Lee, B Graziano, G AF Lee, B Graziano, G TI A two-state model of hydrophobic hydration that produces compensating enthalpy and entropy changes SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-DYNAMICS; NONPOLAR SOLUTES; MONTE-CARLO; WATER; SOLVATION; THERMODYNAMICS; SOLVENT; HEATS; VIEW AB Many of the mixture models of water seek to explain the large free energy change associated with hydrophobic hydration by means of changes in the number and character of the hydrogen bonds in water. Al of these models, regardless of detail, are in clash with the idea that hydrogen bond rearrangements will produce changes in both enthalpy and entropy, which largely compensate to produce little net free energy change. One of the simplest and most recent of these mixture models is Muller's two-state model, which produces small enthalpy and large negative entropy changes. In this paper, Muller's model is examined in detail. It is found that only slight changes are required in order for the model to produce nearly compensating enthalpy and entropy changes. C1 UNIV NAPLES FEDERICO II,DIPARTIMENTO CHIM,I-80134 NAPLES,ITALY. RP Lee, B (reprint author), NCI,MOLEC BIOL LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 4B15,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. OI Graziano, Giuseppe/0000-0001-6935-8172 NR 35 TC 156 Z9 156 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 5 PY 1996 VL 118 IS 22 BP 5163 EP 5168 DI 10.1021/ja9538389 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA UP538 UT WOS:A1996UP53800001 ER PT J AU BallardBarbash, R Potosky, AL Harlan, LC Nayfield, SG Kessler, LG AF BallardBarbash, R Potosky, AL Harlan, LC Nayfield, SG Kessler, LG TI Factors associated with surgical and radiation therapy for early stage breast cancer in older women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; SEGMENTAL-MASTECTOMY; GEOGRAPHIC-VARIATION; AXILLARY DISSECTION; ELDERLY WOMEN; AGE; SURGERY; CARE; RADIOTHERAPY; PATTERNS AB Background: In addition to demographic and health care-related characteristics, the age and physiologic status of women at the time of breast cancer diagnosis have been reported to influence receipt of standard treatments. Previous studies of the influence of age and comorbidity have not examined whether other patient-, region-, or health care-related characteristics altered the association of age and comorbidity with type of treatment received. Purpose: This study examined factors associated with receipt of breast-conserving surgery and radiation therapy, both of which are recommended treatments for breast cancer, among a cohort of 18 704 women aged 65 years or more who had breast cancer diagnosed during the period from 1985 through 1989. Methods: A data file linking Medicare claims records to data from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute was utilized. Logistic regression analysis was used to examine associations between patient, region, and hospital characteristics and the receipt of specific treatments. The likelihood test was used to assess the significance of observed associations (expressed as odds ratios [ORs]). Because of multiple comparisons, only those ORs with two-sided P values <.01 were considered statistically significant. Results: The frequency of breast-conserving surgery was highest (54%) among women aged 80 years or more, who had two or more comorbid conditions and stage I disease. However, in general, the receipt of radiation therapy among women undergoing breast-conserving surgery declined markedly with age, irrespective of comorbidity status and disease stage. Between the ages of 65-69 years and 80 years or older, radiation therapy declined from 77% to 24% among women with no comorbid conditions and from 50% to 12% among women with two or more comorbid conditions. In regression models that included hospital, region, and patient characteristics as variables, age and comorbidity remained independently associated with the receipt of radiation therapy (OR = 0.12 and 95% confidence interval [CI] = 0.10-0.14 for women aged 80 years or more compared with women 65-69 years of age and OR of 0.33 [95 % CI = 0.24-0.46] for women with two or more comorbid conditions versus no comorbid conditions). Conclusions: After adjustment for multiple clinical and nonclinical factors influencing treatment, chronologic age remains an important independent factor associated with the receipt of radiation therapy after breast-conserving surgery among women aged 65 years or more who were diagnosed with early stage breast cancer. Implications: Future studies should determine whether these differences in treatment patterns among older women result in increased morbidity (e.g., from recurrence), shortened disease-free or overall survival, or decreased quality of life. C1 NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. OFF SURVEILLANCE & BIOMETR FOOD & DRUG ADM,CTR DEVICES & RADIOL HLTH,GAITHERSBURG,MD. RP BallardBarbash, R (reprint author), NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,RM 343,BETHESDA,MD 20892, USA. NR 60 TC 286 Z9 287 U1 1 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 5 PY 1996 VL 88 IS 11 BP 716 EP 726 DI 10.1093/jnci/88.11.716 PG 11 WC Oncology SC Oncology GA UN481 UT WOS:A1996UN48100009 PM 8637025 ER PT J AU Rybak, SM Pearson, JW Fogler, WE Volker, K Spence, SE Newton, DL Mikulski, SM Ardelt, W Riggs, CW Kung, HF Longo, DL AF Rybak, SM Pearson, JW Fogler, WE Volker, K Spence, SE Newton, DL Mikulski, SM Ardelt, W Riggs, CW Kung, HF Longo, DL TI Enhancement of vincristine cytotoxicity in drug-resistant cells by simultaneous treatment with Onconase, an antitumor ribonuclease SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID P-30 PROTEIN; MONOCLONAL-ANTIBODY; TUMOR-CELLS; CANCER; TAMOXIFEN; XENOGRAFT; SURVIVAL; REVERSAL; EMBRYOS; AGENTS AB Background: Onconase, a protein isolated from oocytes and early embryos of the frog Rana pipiens, shares extensive homology with bovine pancreatic ribonuclease (RNase A) and possesses similar enzyme activity, Onconase is cytotoxic toward cancer cells in vitro and exhibits antitumor activity in animal models, In addition, Onconase has been shown to enhance the cytotoxic activity of some chemotherapeutic agents in vitro, Purpose: We studied interactions between the cytotoxic effects of Onconase and the chemotherapeutic agent vincristine (VCR) in the treatment of drug-sensitive and multidrug-resistant human colon carcinoma cells in vitro and in mice, Methods: Transplantable human colon carcinoma cells (HT-29(par) cells) were infected with a retrovirus containing human mdr1 (also known as MDR1 and PGY1) complementary DNA (encoding P-glycoprotein [P-gp]), and clones that were cross-resistant to colchicine, doxorubicin, and vinblastine were selected (HT-29(mdr1) cells), Drug-resistant HT-29(mdr1) cells and drug-sensitive HT-29(par) parental cells were treated with Onconase and/or VCR in vitro at varying concentrations to measure the effects on protein synthesis and cell viability, The impact of Onconase on VCR accumulation in both types of cells was determined in the presence or absence of MRK-16, an anti-P-gp monoclonal antibody capable of reversing the multidrug-resistant phenotype, The antitumor effects of Onconase and/or VCR treatment were assessed in nude mice bearing established HT-29(par) or HT-29(mdr1) intraperitoneal tumors, IC50 values (drug concentrations resulting in 50% inhibition of protein synthesis or cell viability) for Onconase and VCR were determined from semilogarithmic dose-response curves; interactions between the cytotoxic effects of these two agents were evaluated using data from protein synthesis inhibition experiments and a two-way analysis of variance, Survival distributions from in vivo experiments were compared using Cox proportional hazards models, Results: The combination of Onconase and VCR yielded enhanced cytotoxicity in vitro that was independent of P-gp expression, Evaluation of the effects of these two compounds on protein synthesis over a wide range of drug concentrations indicated possible synergistic interactions (i.e., greater than additive effects) in both drug-resistant and drug-sensitive cells, The enhancement of VCR cytotoxicity was dependent on Onconase enzyme activity and was not associated with increased intracellular levels of VCR, Simultaneous treatment of mice bearing HT-29(par) tumors with Onconase and VCR did not extend their median survival time (MST) significantly (MST with VCR = 66 days; MST with VCR plus Onconase = 69 days; two-tailed P = .57); however, the MST of mice with HT-29(mdr1) tumors was extended significantly by this treatment (MST with VCR = 44 days; MST with VCR plus Onconase = 66 days; two-tailed P < .001). Conclusion: Combined administration of Onconase and VCR yields enhanced cytotoxicity in vitro and in vivo against human colon carcinoma cells that overexpress the mdr1 gene. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV,FREDERICK,MD 21702. ALFACELL CORP,BLOOMFIELD,NJ. RP Rybak, SM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB BIOCHEM PHYSIOL,BLDG 567,FREDERICK,MD 21702, USA. NR 28 TC 64 Z9 70 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 5 PY 1996 VL 88 IS 11 BP 747 EP 753 DI 10.1093/jnci/88.11.747 PG 7 WC Oncology SC Oncology GA UN481 UT WOS:A1996UN48100013 PM 8637029 ER PT J AU Helzlsouer, KJ Harris, EL Parshad, R Perry, HR Price, FM Sanford, KK AF Helzlsouer, KJ Harris, EL Parshad, R Perry, HR Price, FM Sanford, KK TI DNA repair proficiency: Potential susceptibility factor for breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PHASE-X-IRRADIATION; FLUOROSCOPIC EXAMINATIONS; CHROMATID DAMAGE; ATAXIA-TELANGIECTASIA; INDIVIDUALS; WOMEN; CHEST; RADIOSENSITIVITY; TUBERCULOSIS; LYMPHOCYTES C1 KAISER PERMANENTE,CTR HLTH RES,PORTLAND,OR. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. NCI,CELLULAR & MOLEC BIOL LAB,DIV CANC ETIOL,BETHESDA,MD 20892. RP Helzlsouer, KJ (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CA 1522, CA 36390] NR 16 TC 96 Z9 96 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 5 PY 1996 VL 88 IS 11 BP 754 EP 755 DI 10.1093/jnci/88.11.754 PG 2 WC Oncology SC Oncology GA UN481 UT WOS:A1996UN48100014 PM 8637030 ER PT J AU Potischman, N Swanson, CA Siiteri, P Hoover, RN AF Potischman, N Swanson, CA Siiteri, P Hoover, RN TI Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER RISK; MASSIVELY OBESE WOMEN; ENDOMETRIAL CANCER; PREMENOPAUSAL WOMEN; STEROID-SECRETION; MENSTRUAL EVENTS; SIZE; SERUM; WEIGHT; GONADOTROPIN RP Potischman, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. NR 29 TC 187 Z9 188 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 5 PY 1996 VL 88 IS 11 BP 756 EP 758 DI 10.1093/jnci/88.11.756 PG 3 WC Oncology SC Oncology GA UN481 UT WOS:A1996UN48100015 PM 8637031 ER PT J AU Kuppusamy, P Wang, PH Zweier, JL Krishna, MC Mitchell, JB Ma, L Trimble, CE Hsia, CJC AF Kuppusamy, P Wang, PH Zweier, JL Krishna, MC Mitchell, JB Ma, L Trimble, CE Hsia, CJC TI Electron paramagnetic resonance imaging of rat heart with nitroxide and polynitroxyl-albumin SO BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE; SPIN LABELS; REPERFUSION INJURY; CONTRAST AGENT; FREE-RADICALS; LIVING CELLS; SUPEROXIDE; ENHANCEMENT; METABOLISM; REDUCTION AB Electron paramagnetic resonance (EPR)(1) imaging utilizing stable nitroxyl radicals is a promising technique for measuring free radical distribution, metabolism, and tissue oxygenation in organs and tissues [Kuppusamy, P., Chzhan, M., Vij, K., Shteynbuk, M., Lefer, D. J., Giannella, E., & Zweier, J. L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 3388-3392]. However, the technique has been limited by the rapid reduction of nitroxide in vivo to its hydroxylamine derivative, a diamagnetic, EPR-inactive species. In this report a novel, polynitroxylated derivative of human serum albumin is shown to be capable of reoxidizing the hydroxylamine back to nitroxide in vivo. Polynitroxyl-albumin (PNA) is shown to be effective in maintaining the signal intensity of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL or TPL) in the ischemic isolated rat heart, allowing the acquisition of high-resolution three-dimensional (3D) EPR images of the heart throughout a prolonged 2.5 h period of global cardiac ischemia. In serial transverse sections of the 3D image, TPL intensity maps of the heart showed cardiac structure with submillimeter resolution. TPL intensities in coronary arteries and myocardium showed that nitroxide concentration decreases with increasing distance from large blood vessels. These results demonstrate that EPR imaging in vivo is possible using nitroxides in conjunction with PNA. In addition to its utility in the emerging technology of EPR imaging, the greatly prolonged half-life of TPL observed in the presence of PNA may facilitate the therapeutic application of nitroxides in a variety of disease processes. C1 JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,MOL & CELLULAR BIOPHYS LABS,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,EPR CTR,BALTIMORE,MD 21224. NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. SYNZYME TECHNOL INC,IRVINE,CA 92718. FU NHLBI NIH HHS [HL-38324, HL-17655, HL-53860] NR 33 TC 73 Z9 75 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 4 PY 1996 VL 35 IS 22 BP 7051 EP 7057 DI 10.1021/bi952857s PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP430 UT WOS:A1996UP43000011 PM 8679530 ER PT J AU Zhu, DM Tekle, E Chock, PB Huang, CY AF Zhu, DM Tekle, E Chock, PB Huang, CY TI Reversible phosphorylation as a controlling factor for sustaining calcium oscillations in HeLa cells: Involvement of calmodulin-dependent kinase II and a calyculin A-inhibitable phosphatase SO BIOCHEMISTRY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CYTOPLASMIC FREE CALCIUM; PROTEIN-KINASE; PHOSPHOLIPASE-C; TRISPHOSPHATE RECEPTOR; INTRACELLULAR CALCIUM; OKADAIC ACID; RAT-BRAIN; NUCLEOTIDE PHOSPHODIESTERASE; SARCOPLASMIC-RETICULUM AB The role of reversible phosphorylation in histamine-induced Ca2+ oscillations in HeLa cells has been investigated by using various activators and inhibitors of protein kinases and phosphatases. Electroporation was employed to introduce impermeable materials into single cells, which proved to be a useful and convenient tool, Of the kinases examined, cAMP-dependent kinase, protein kinase C, and calmodulin-dependent kinase II (CaMK II), only CaMK II was essential. When added during oscillations, both W-7, a calmodulin antagonist, and KN-62, a specific CaMK II inhibitor, caused one large Ca2+ spike before halting the process. Introduction of the Ca2+/calmodulin-independent catalytic domain of CaMK II into the cells forestalled their response to histamine. These results show that intracellular Ca2+ cannot oscillate when CaMK II is locked in either the inactive or the stimulated state. External Ca2+ electroporated into cells preloaded with the catalytic domains was quickly removed (but not when the cells were pretreated with the endoplasmic reticulum Ca2+-ATPase inhibitor, tapsigargin), indicating that the ATP-driven Ca2+ pump was somehow activated by CaMK II. Protein phosphatase inhibitors calyculin A and okadaic acid abolished ongoing oscillations and, when added at low concentrations, prolonged the interspike interval. Immunoprecipitation experiments with P-32(i)-labeled cells provided the first evidence that inositol 1,4,5-trisphosphate receptor (IP(3)R) was phosphorylated by CaMK II in vivo. The extent of phosphorylation was increased in the presence of histamine, significantly enhanced by calyculin A, and greatly reduced by W-7. Our observations are consistent with the concept that repetitive phosphorylation-dephosphorylation cycles regulating IP(3)R and Ca2+ pumps are a controlling factor for sustained Ca2+ oscillations in HeLa, and possibly other, cells. C1 NHLBI,IR,LB,NIH,BETHESDA,MD 20892. NR 67 TC 45 Z9 45 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 4 PY 1996 VL 35 IS 22 BP 7214 EP 7223 DI 10.1021/bi952471h PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP430 UT WOS:A1996UP43000031 PM 8679550 ER PT J AU Matochik, JA Zametkin, AJ Cohen, RM Hauser, P Weintraub, BD AF Matochik, JA Zametkin, AJ Cohen, RM Hauser, P Weintraub, BD TI Abnormalities in sustained attention and anterior cingulate metabolism in subjects with resistance to thyroid hormone SO BRAIN RESEARCH LA English DT Article DE positron emission tomography; glucose metabolism; attention; anterior cingulate; thyroid receptor beta ID ERBA-BETA GENE; GENERALIZED RESISTANCE; HUMAN-BRAIN; LOCALIZATION; KINDREDS; HYPERACTIVITY; MUTATIONS; RECEPTOR; SYSTEM AB Attention deficit disorders are a frequent manifestation of resistance to thyroid hormone (RTH), a disorder caused by mutations in the hormone-binding domain of the human thyroid hormone receptor beta gene. Positron emission tomography was used to measure cerebral glucose metabolism in regions known to be biological determinants of sustained attention in 13 adult RTH and 13 unaffected subjects. Compared to the control group, performance on a continuous auditory discrimination task was severely impaired in the RTH subjects, while metabolism was higher both in the right parietal cortex and the anterior cingulate gyrus. Abnormally high functional activity of the anterior cingulate during sustained attention may be associated with a decreased signal-to-noise ratio for the neural processing of task stimuli in subjects with RTH. C1 UNIV MARYLAND,SCH MED,VET ADM MED CTR,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DIV ENDOCRINOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,INST HUMAN VIROL,BALTIMORE,MD 21201. RP Matochik, JA (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,RM 1A05,BETHESDA,MD 20892, USA. NR 23 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 3 PY 1996 VL 723 IS 1-2 BP 23 EP 28 DI 10.1016/0006-8993(96)00177-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA UU938 UT WOS:A1996UU93800003 PM 8813378 ER PT J AU Maderdrut, JL Lazar, G Kozicz, T Merchenthaler, I AF Maderdrut, JL Lazar, G Kozicz, T Merchenthaler, I TI Distribution of neuromedin U-like immunoreactivity in the central nervous system of Rana esculenta SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Amphibia; evolution; hypothalamus; immunocytochemistry; peptides ID PROENKEPHALIN-DERIVED PEPTIDES; P-LIKE IMMUNOREACTIVITY; HORMONE ALPHA-MSH; RAT-BRAIN; SUBSTANCE-P; SPINAL-CORD; GASTROINTESTINAL-TRACT; DESCENDING PATHWAYS; MYENTERIC PLEXUS; SOLITARY TRACT AB The distribution of perikarya and nerve fibers containing neuromedin U-like immunoreactivity in the brain of Rana esculenta was determined with an antiserum directed toward the carboxyl terminus of the peptide. In the telencephalon, immunoreactive perikarya were found in the olfactory bulb, the medial sept um, and the diagonal band. In the diencephalon, labeled perikarya were detected in the anterior and posterior preoptic areas, the dorsal nucleus of the hypothalamus, the caudal pare of the infundibulum, and the posterior tuberculum. In the mesencephalon, immunoreactive cell bodies were found only in the laminar nucleus of the torus semicircularis and the anterodorsal tegmental nucleus. In the rhombencephalon, labeled perikarya were detected in the secondary visceral nucleus, the cerebellar nucleus, the central gray, and the nucleus of the solitary tract. Immunoreactive nerve fibers were observed in all areas of the brain that contained labeled perikarya. The densest accumulations were found in the nucleus accumbens; the dorsal part of the lateral septum; the periventricular region of the ventral thalamus; the lateral part of the infundibulum; the anterodorsal, anteroventral, posterodorsal, and posteroventral tegmental nuclei; and the periaqueductal region of the tegmentum. The distribution of neuromedin U-like immunoreactivity in the frog brain was substantially different from the distribution described for the rodent brain. (C) 1996 Wiley-Liss, Inc. C1 TULANE UNIV,HEBERT CTR,US JAPAN BIOMED RES LABS,DEPT MED,BELLE CHASSE,LA 70037. UNIV PECS,SCH MED,DEPT ANAT,H-7643 PECS,HUNGARY. NIEHS,FUNCT MORPHOL SECT,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. WOMENS HLTH RES INST,WYETH AYERST RES,RADNOR,PA 19087. RI Kozicz MD, PhD, Tamas/G-3161-2012; Kozicz, Tamas/N-5154-2014 OI Kozicz MD, PhD, Tamas/0000-0001-6915-4364; NR 46 TC 9 Z9 9 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 3 PY 1996 VL 369 IS 3 BP 438 EP 450 DI 10.1002/(SICI)1096-9861(19960603)369:3<438::AID-CNE8>3.0.CO;2-6 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UM590 UT WOS:A1996UM59000008 PM 8743423 ER PT J AU Clerici, M Sarin, A Berzofsky, JA Landay, AL Kessler, HA Hashemi, F Hendrix, CW Blatt, SP Rusnak, J Dolan, MJ Coffman, RL Henkart, PA Shearer, GM AF Clerici, M Sarin, A Berzofsky, JA Landay, AL Kessler, HA Hashemi, F Hendrix, CW Blatt, SP Rusnak, J Dolan, MJ Coffman, RL Henkart, PA Shearer, GM TI Antigen-stimulated apoptotic T-cell death in HIV infection is selective for CD4+ T cells, modulated by cytokines and effected by lymphotoxin SO AIDS LA English DT Article DE apoptosis; CD4+ T cells; cytokines; HIV infection ID SEROPOSITIVE INDIVIDUALS; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; LYMPHOCYTES-T; AIDS; DYSFUNCTION; RECOGNITION; DEPLETION AB Objective: To characterize the mechanism of in vitro antigen-induced apoptotic T-cell death in the peripheral blood mononuclear cells (PBMC) of HIV-1-infected individuals. Design and methods: PBMC from HIV-1-infected and uninfected individuals were unstimulated or stimulated with HIV-1 envelope synthetic peptides (Env) or influenza A virus to determine the extent of antigen-stimulated apoptotic T-cell death, whether this death was limited to the CD4+ subset, and the effects of cytokines on T-cell death. Death was assessed by apoptotic: nuclear morphology after 7 days of culture by fluorescence microscopy using a DNA-specific dye. Transwell cultures and supernatant transfers were utilized to test whether a soluble factor produced by HIV-positive PBMC induced death of HIV-negative T cells. Exogenous cytokines [interleukin (IL)12, interferon (IFN)-gamma, IL-4 and IL-10], as well as antibodies against endogenously produced cytokines (IL-4, IL-10, IL-12, and lymphotoxin) were tested for their ability to modulate death. Results: Antigenic stimulation induced death in PBMC from HIV-positive donors, but not in PBMC from HIV-negative donors. Antigen-stimulated death was seen in CD4+ but not CD8+ T-cell subset from the HIV-positive patients. Apoptotic death was blocked by IL-12, IFN-gamma, anti-IL-4, anti-IL-10, and anti-lymphotoxin, but not by anti-IL-12. Transwell and supernatant transfer experiments indicated that antigen-stimulated HIV-positive PBMC produced a factor that killed T-cell blasts. The factor was inhibited by anti-lymphotoxin, but not by anti-IL-10. Conclusions: Stimulation of HIV-positive PBMC with CD4-dependent antigens results in selective death of CD4+ T cells that is modulated by cytokines. Our results suggest that apoptotic death is not limited to HIV-infected or HIV-specific T cells, but occurs in bystander cells. Lymphotoxin is a mediator of antigen-stimulated T-cell death in this in vitro model. C1 NCI,NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,NIH,METAB BRANCH,BETHESDA,MD 20892. UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. RUSH MED COLL,DEPT MED,CHICAGO,IL 60612. RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 44 TC 62 Z9 63 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUN PY 1996 VL 10 IS 6 BP 603 EP 611 DI 10.1097/00002030-199606000-00005 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UN950 UT WOS:A1996UN95000005 PM 8780814 ER PT J AU DeSimone, C Cifone, MG Alesse, E Steinberg, SM DiMarzio, L Moretti, S Famularo, G Boschini, A Testi, R AF DeSimone, C Cifone, MG Alesse, E Steinberg, SM DiMarzio, L Moretti, S Famularo, G Boschini, A Testi, R TI Cell-associated ceramide in HIV-1-infected subjects SO AIDS LA English DT Letter C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,ROME,ITALY. RP DeSimone, C (reprint author), UNIV LAQUILA,DEPT EXPTL MED,LAQUILA,ITALY. RI Di Marzio, Luisa/H-9969-2012 NR 10 TC 17 Z9 17 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUN PY 1996 VL 10 IS 6 BP 675 EP 676 DI 10.1097/00002030-199606000-00014 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UN950 UT WOS:A1996UN95000014 PM 8780823 ER PT J AU Higley, JD Suomi, SJ Linnoila, M AF Higley, JD Suomi, SJ Linnoila, M TI A nonhuman primate model of type II excessive alcohol consumption .1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE serotonin; norepinephrine type II alcoholism; aggression; antisocial personality ID MONKEYS MACACA-MULATTA; DISRUPTIVE BEHAVIOR DISORDERS; CSF MONOAMINE METABOLITE; RHESUS-MONKEYS; HOMOVANILLIC-ACID; SUBSTANCE USE; BRAIN; CHILDREN; AGE; PERSONALITY AB Developmental, biochemical, and behavioral concomitants of excessive alcohol consumption were investigated using a nonhuman primate model. The variables of interest were: (1) interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) from infancy to adulthood, (2) effect of parental deprivation early in life on adult CSF 5-HIAA concentrations; (3) correlations between CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations and alcohol consumption; and (4) correlation between the frequency of competent social behaviors and alcohol consumption. Twenty-nine rhesus macaques were reared for their first 6 months either with their mothers or without adults in peer-only conditions. At 6 and 50 months of age, each subject underwent a series of four, 4-day social separations. Cisternal CSF was sampled before and during the first and last separations; concomitantly, observational data were collected on social dominance behavior in the home-cage. When they reached 50 months of age, the monkeys were provided free access to a palatable alcohol solution daily for 1-hr periods before, during, and after the social separations. Before and after the 50-month separations, data were collected on all types of social behavior in the home-cage. Results showed that peer-reared subjects consumed more alcohol than mother-reared subjects during baseline conditions. Mother-reared subjects, however, increased their rates of consumption to equal peer-reared subjects' rates of consumption during the conditions of a social separation stressor, Peer-reared subjects also exhibited lower CSF 5-HIAA concentrations in infancy and adulthood than their mother-reared counterparts, With rearing condition held constant, interindividual differences in CSF 5-HIAA, MHPG, and homovanillic acid were stable from infancy to adulthood, and high rates of alcohol were consumed by the young adult monkeys with low CSF 5-HIAA and MHPG concentrations, particularly when the CSF was obtained during the social separations. High rates of alcohol consumption were also observed in subjects with infrequent social interactions and less competent social behaviors. In contrast to the human data, we found no gender differences in rates of alcohol consumption, nor in the correlations between alcohol consumption and the other variables. With some exceptions, findings from the study are generally consistent with predictions from Cloninger's type II model of excessive alcohol consumption in men with low CSF 5-HIAA, who also exhibit impaired impulse control and violent and antisocial behaviors. C1 NIAAA,CLIN STUDIES LAB,PRIMATE UNIT,DIV INTRAMURAL CLIN & BIOL RES,ROCKVILLE,MD 20852. RP Higley, JD (reprint author), NICHHD,COMPARAT ETHOL LAB,NIH,ANIM CTR,POB 529,BLDG 112,POOLESVILLE,MD 20837, USA. NR 92 TC 141 Z9 141 U1 3 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1996 VL 20 IS 4 BP 629 EP 642 DI 10.1111/j.1530-0277.1996.tb01665.x PG 14 WC Substance Abuse SC Substance Abuse GA UT999 UT WOS:A1996UT99900004 PM 8800378 ER PT J AU Higley, JD Suomi, SJ Linnoila, M AF Higley, JD Suomi, SJ Linnoila, M TI A nonhuman primate model of type II alcoholism .2. Diminished social competence and excessive aggression correlates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE type II alcoholism; serotonin; norepinephrine; aggression; antisocial personality ID MONKEYS MACACA-MULATTA; IMPULSIVE FIRE SETTERS; MALE VERVET MONKEYS; RHESUS-MONKEYS; MONOAMINE METABOLITES; AMINE METABOLITES; CHILDHOOD PERSONALITY; VIOLENT OFFENDERS; SUBSTANCE USE; BEHAVIOR AB The purpose of this study was to develop an animal model for behavioral features of type II, early-onset alcohol abuse. To perform this research, cerebrospinal fluid (CSF) monoamine metabolite concentrations and home-cage social behaviors of 29 rhesus macaque subjects were examined in a 4-year longitudinal study. Half of the monkeys were reared for their first 6 months with their mothers, and the other half were reared without adults, instead with access only to monkeys of similar age. When the subjects were 6 months old, and again when they were 50 months old, they underwent a series of four, 4-day social separations. We obtained cisternal CSF before and during the first and last separation of each series to quantify 5-hydroxy-indoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylgycol (MHPG), and homovanillic acid concentrations. After the 6-month separations, subjects were placed into social groups, and social dominance rankings were assessed. Before and after the 50-month separations, social dominance rankings were evaluated again, and home-cage aggression and social behavior data were collected. Over the 3 1/2 years between CSF samplings, records were maintained of subjects' removal from their social groups for excessive aggression or treatment for wounding. Our results showed that among infants, reduced CSF 5-HIAA was correlated with low social dominance, As young adults, subjects from both rearing groups with low CSF 5-HIAA and MHPG concentrations exhibited reduced rates of social interaction and low social dominance rankings. In addition, peer-reared subjects with low CSF 5-HIAA concentrations exhibited inept social behaviors, and were frequently removed from their social groups for excessive aggression and deviant social behaviors. From these results, we conclude that the peer-rearing paradigm aggravates the untoward social consequences associated with low OSF 5-HIAA concentrations over and beyond reducing CSF 5-HIAA concentrations, suggesting that early experiences may contribute to CNS serotonin changes that increase the disposition to type II-related behaviors. C1 NIAAA,CLIN STUDIES LAB,PRIMATE UNIT,DIV INTRAMURAL CLIN & BIOL RES,ROCKVILLE,MD 20852. RP Higley, JD (reprint author), NICHHD,COMPARAT ETHOL LAB,NIH,ANIM CTR,POB 529,BLDG 112,POOLESVILLE,MD 20837, USA. RI McCarthy, Jodie/B-5760-2012 NR 70 TC 101 Z9 101 U1 2 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1996 VL 20 IS 4 BP 643 EP 650 DI 10.1111/j.1530-0277.1996.tb01666.x PG 8 WC Substance Abuse SC Substance Abuse GA UT999 UT WOS:A1996UT99900005 PM 8800379 ER PT J AU Kidd, KK Pakstis, AJ Castiglione, CM Kidd, JR Speed, WC Goldman, D Knowler, WC Lu, RB BonneTamir, B AF Kidd, KK Pakstis, AJ Castiglione, CM Kidd, JR Speed, WC Goldman, D Knowler, WC Lu, RB BonneTamir, B TI DRD2 haplotypes containing the TaqI A1 allele: Implications for alcoholism research SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE DRD2; alcoholism; haplotype; polymorphism; population genetics ID DOPAMINE D2 RECEPTOR; DNA POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; POPULATION; GENE; FREQUENCIES; EVOLUTION; INDIANS AB In recent years, a possible role of the dopamine D-2 receptor (DRD2) locus in the etiology of alcoholism has been the focus of considerable attention. The literature now contains a mix of association studies with positive and negative conclusions. Various methodological flaws undermine the claims in many of the studies that conclude a positive association exists between alcoholism and the DRD2*A1 allele at the Taql ''A'' site. Although the studies with negative findings have more often come from studies using better analytic methodology, satisfactory resolution of whether or not genetic variation at the DRD2 locus plays some role in the etiology of alcoholism is unlikely to come from additional studies of the kind conducted thus far; an approach enlightened by a more thorough understanding of the population genetics of DRD2 and the phylogenetic origins of the DRD2 alleles is one alternative. If genetic variation at the DRD2 locus affects susceptibility to alcoholism, then such variation has a mutational and evolutionary history that can be traced with the aid of the various genetic polymorphisms that have been identified at the DRD2 locus. In this study, a third Taql restriction fragment-length polymorphism at DRD2, the Taql ''D'' site, has been converted to polymerase chain reaction-based typing and its frequencies determined in 22 populations from around the world. Haplotypes defined by the polymorphisms at the Taql ''B'' and ''A'' sites, and the short tandem repeat polymorphism in intron 2 have been constructed and the diversity of haplotypes containing the DRD2*A1 allele examined for all 22 populations. The ancestral origins of the three Taql polymorphisms have also been determined by sequencing the homologous regions in other higher primates. Because A1-containing haplotypes in populations of European, Middle Eastern, and African origin show considerable diversity within and among populations, properly designed association studies in populations descended from those areas of the world need to use haplotypes, not a singleallelic system, and need to use appropriate methods to compensate for the near impossibility of genetically matching unrelated control samples. C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,NIH,PHOENIX,AZ. NATL DEF MED CTR,TRISERV GEN HOSP,DEPT PSYCHIAT,TAIPEI,TAIWAN. TEL AVIV UNIV,SACKLER FAC MED,DEPT HUMAN GENET,IL-69978 TEL AVIV,ISRAEL. RP Kidd, KK (reprint author), YALE UNIV,SCH MED,DEPT GENET,333 CEDAR ST,NEW HAVEN,CT 06520, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA09379]; NIMH NIH HHS [MH30929, MH39239] NR 45 TC 63 Z9 63 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1996 VL 20 IS 4 BP 697 EP 705 DI 10.1111/j.1530-0277.1996.tb01674.x PG 9 WC Substance Abuse SC Substance Abuse GA UT999 UT WOS:A1996UT99900013 PM 8800387 ER PT J AU Dawson, DA AF Dawson, DA TI Correlates of past-year status among treated and untreated persons with former alcohol dependence: United States, 1992 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; treatment; natural history of alcoholism; outcome ID FOLLOW-UP; CONTROLLED DRINKING; PROBLEM DRINKERS; NATURAL-HISTORY; NON-ABSTINENT; GOAL; MEN AB Past-year status was investigated in a sample of 4,585 adults with prior DSM-IV alcohol dependence, Those who had and had not received treatment for alcohol problems were compared in terms of past-year status and its correlates, to see if the experience of treatment samples would be reflective of the course of alcoholism in the general population. In the past year, 27.8% of the total sample met the criteria for alcohol abuse or dependence, 22.3% were abstinent, and 49.9% were drinkers who did not satisfy the criteria for either abuse or dependence. Persons who had been treated for alcohol problems were about twice as likely to be abstainers as those who had not been treated (38.8% vs, 16.4%), but only about half as likely to fall into the past-year category of drinking without abuse or dependence (28.0% vs. 57.8%). These differentials were of constant magnitude, regardless of the interval since the onset of dependence, For the sample as a whole, persons who had received treatment were slightly more likely than their untreated counterparts to have had alcohol abuse or dependence in the past year (33.2% vs. 25.8%), and this differential increased with the interval since the onset of dependence. The odds of both past-year abstinence and drinking without abuse or dependence were decreased by male gender, Black race, rapidity of the onset of dependence and ethanol intake per drinking day, and were increased by ever having been married and by later ages at onset of dependence, The odds of drinking without abuse or dependence relative to abstinence were increased by college attendance and reduced by the number of dependence symptoms, and having been a daily drinker was associated with increased odds of past-year abstinence. Treatment history modified the associations between past-year status and race, marital and educational status, number of past alcohol problems, and rapidity of onset of dependence and age at onset. These results suggest that treatment studies may not be generalizable to alcoholics who do not seek treatment. RP Dawson, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,WILLCO BLDG,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 34 TC 81 Z9 82 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1996 VL 20 IS 4 BP 771 EP 779 DI 10.1111/j.1530-0277.1996.tb01685.x PG 9 WC Substance Abuse SC Substance Abuse GA UT999 UT WOS:A1996UT99900024 PM 8800398 ER PT J AU Jansen, MA Glynn, T Howard, J AF Jansen, MA Glynn, T Howard, J TI Prevention of alcohol, tobacco and other drug abuse - Federal efforts to stimulate prevention research SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article AB This article first provides an overview of a sequential approach to conducting research. This model and similar sequential approaches have sometimes been referred to as the phases of research model. Next, the article offers a summary of what has been learned from this research and offers some thoughts on what is needed in future prevention research efforts, particularly in alcohol, tobacco, and other drug abuse prevention. The research agendas of three federal agencies are provided, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Cancer Institute (NCI) and the Center for Substance Abuse Prevention (CSAP). C1 NCI, CANC PREVENT & CONTROL RES BRANCH, NIH, US DEPT HHS, BETHESDA, MD 20892 USA. NIAAA, NIH,US DEPT HHS,PREVENT RES BRANCH, DIV CLIN & PREVENT RES, ROCKVILLE, MD 20852 USA. RP Jansen, MA (reprint author), SAMHSA, US DEPT HHS, OFF SCI ANAL, CTR SUBST ABUSE PREVENT, ROCKVILLE, MD 20857 USA. NR 66 TC 6 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 EI 1552-3381 J9 AM BEHAV SCI JI Am. Behav. Sci. PD JUN PY 1996 VL 39 IS 7 BP 790 EP 807 DI 10.1177/0002764296039007003 PG 18 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA UM899 UT WOS:A1996UM89900002 ER PT J AU Donaldson, SI Sussman, S MacKinnon, DP Severson, HH Glynn, T Murray, DM Stone, EJ AF Donaldson, SI Sussman, S MacKinnon, DP Severson, HH Glynn, T Murray, DM Stone, EJ TI Drug abuse prevention programming - Do we know what content works? SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article ID 6-YEAR FOLLOW-UP; OF-THE-ART; SMOKING PREVENTION; CIGARETTE-SMOKING; ADOLESCENT SMOKING; META-ANALYSIS; EDUCATION; ALCOHOL; EFFICACY; PROJECT AB This article summarizes the theoretical underpinnings, substantive contents and limitations of comprehensive social-influences-based drug abuse prevention programming. This type of programming has produced the most consistently successful preventive effects. There is some evidence that one major parr of these programs changing social norms, is an essential ingredient for successful drug abuse prevention programming. Research suggests that these effects may not be contingent on the use of refusal assertion training, a prototype activity of social-influences-based prevention programs. Because programs when disseminated to the public, often contain only a subset of lessons from the social influences curriculum there remains the potential error of implementing a combination of lessons that may not be effective. Further there is evidence that other types of prevention programming such as physical consequences programming, may be successful in some situations Finally social-influences-based programming may not be as effective with some subpopulations such as high-risk youths. C1 UNIV SO CALIF, LOS ANGELES, CA 90089 USA. ARIZONA STATE UNIV, TEMPE, AZ 85287 USA. UNIV OREGON, EUGENE, OR 97403 USA. NCI, NIH, US DEPT HHS, CANC PREVENT & CONTROL RES BRANCH, BETHESDA, MD 20892 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. RP Donaldson, SI (reprint author), CLAREMONT GRAD SCH, CTR ORG & BEHAV SCI, 123 E 8TH ST, CLAREMONT, CA 91711 USA. RI MacKinnon, David /D-8727-2013 NR 78 TC 63 Z9 63 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 EI 1552-3381 J9 AM BEHAV SCI JI Am. Behav. Sci. PD JUN PY 1996 VL 39 IS 7 BP 868 EP 883 DI 10.1177/0002764296039007008 PG 16 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA UM899 UT WOS:A1996UM89900007 ER PT J AU Pentz, MA Bonnie, RJ Shopland, DR AF Pentz, MA Bonnie, RJ Shopland, DR TI Integrating supply and demand reduction strategies for drug abuse prevention SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article; Proceedings Paper CT Conference on Tobacco, Alcohol and Other Drug Abuse Prevention - Research Directions and Program Policy Implications CY JAN, 1994 CL IRVINE, CA ID ADOLESCENT SMOKING; PROJECT; ALCOHOL; PROGRAM; CIGARETTES; YOUTH AB Historically demand and supply reduction approaches to the prevention and control of tobacco, alcohol and other drug abuse have been treated as independent efforts in the United States, vying for public attention and funding. Separate reviews of research suggest that the more effective components of each approach can reduce potential drug use by 20% to 40% for 3 years and sometimes longer. Review of theories relevant to behavior change suggest that integrating the two approaches could increase this proportion to 40% to 50% for longer periods by synergistically affecting community anti-drug use norms and compliance. This article briefly reviews demand and supply reduction approaches to drug abuse prevention and presents hypothetical models of change in drug use behavior based on program and policy interventions that are introduced sequentially into communities. C1 UNIV VIRGINIA, CHARLOTTESVILLE, VA 22903 USA. NCI, INST WIDE SMOKING & TOBACCO CONTROL PROGRAM, BETHESDA, MD 20892 USA. RP Pentz, MA (reprint author), UNIV SO CALIF, DEPT PREVENT MED, 1540 ALCAZAR AVE, SUITE 207, LOS ANGELES, CA 90033 USA. NR 30 TC 16 Z9 16 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 EI 1552-3381 J9 AM BEHAV SCI JI Am. Behav. Sci. PD JUN PY 1996 VL 39 IS 7 BP 897 EP 910 DI 10.1177/0002764296039007010 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA UM899 UT WOS:A1996UM89900009 ER PT J AU Kumar, S Krenacs, L Otsuki, T Kumar, D Harris, CA Wellmann, A Jaffe, ES Raffeld, M AF Kumar, S Krenacs, L Otsuki, T Kumar, D Harris, CA Wellmann, A Jaffe, ES Raffeld, M TI bcl-1 rearrangement and cyclin D1 protein expression in multiple lymphomatous polyposis SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE gastrointestinal lymphoma; multiple lymphomatous polyposis; mantle cell lymphoma; bcl-1 rearrangement; polymerase chain reaction; cyclin D1 protein expression ID GASTROINTESTINAL-TRACT; CENTROCYTIC LYMPHOMA; CELL AB Multiple lymphomatous polyposis (MLP), characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract, is believed to represent CI involvement by mantle cell lymphoma (MCL), primarily based on its histologic and immunophenotypic similarities with MCL. However, rearrangement of the bcl-1 locus, the molecular lesion characteristic of MCL, has not been investigated in this group of patients. The authors evaluated the morphologic, immunophenotypic, and molecular features of 18 cases of MLP and 8 B-cell lymphomas involving the GI tract (including 6 MALT lymphomas). All MLP cases presented with GI disease, and were histologically similar to MCL. DNA extracted from formalin-fixed, paraffin-embedded tissue was analyzed for evidence of bcl-1 rearrangement by PCR, using chromosome 11 specific and consensus JH primers. Amplifiable DNA,vas obtained in 24 of 26 cases (16 of 18 MLP cases and 8 of 8 controls). bcl-1 rearrangement was detected in 6 of 16 cases (38%), subsequently confirmed by sequencing of the breakpoint region, and in 0 of 8 controls. Immunostaining for cyclin D1 was positive in 14 of 18 MLPs, including the 6 bcl-1 rearranged cases and negative in 6 of 6 evaluable controls. The detection of bcl-1 rearrangement and cyclin D1 expression in cases of MLP supports the view that MLP represents primary MCL of the CI tract. These techniques may also be helpful in differentiating MLP from other GI lymphomas, particularly low grade lymphomas of MALT, when only small routinely fixed endoscopic biopsies are available. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. UNIV MARYLAND,MED SYST,DIV ANAT PATHOL,BALTIMORE,MD 21201. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 23 TC 37 Z9 39 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 1996 VL 105 IS 6 BP 737 EP 743 PG 7 WC Pathology SC Pathology GA UQ496 UT WOS:A1996UQ49600013 PM 8659449 ER PT J AU Engler, HD Fahle, GA Gill, VJ AF Engler, HD Fahle, GA Gill, VJ TI Clinical evaluation of the BacT/Alert and isolator aerobic blood culture systems SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE blood culture; aerobic bacteremia; BacT/Alert; isolator ID LYSIS-CENTRIFUGATION; BACT ALERT; TUBE AB The BacT/Alert (BTA) (Organon Teknika, Durham, NC) and Isolator 10 (ISO) (Wampole Laboratories, Cranbury, NJ) blood culture systems were evaluated for their ability to detect aerobic and facultatively anaerobic microorganisms in blood of adult patients. For each culture 8 mt of blood was inoculated into both the aerobic standard BTA bottle and the ISO tube. Of 7,259 paired culture sets, 1,168 organisms were recovered, and 667 (57.1%) of these were considered clinically significant. This represented 540 clinically significant positive cultures from 266 patients. Of the significant isolates, 410 were recovered by both systems, 108 by BTA only and 149 by ISO only (P < .025). Overall, the BTA detected 77.7% of the significant isolates, whereas ISO detected 83.8%. The ISO recovered significantly more isolates of Staphylococcus aureus (P = .0001), coagulase-negative Staphylococcus spp (P < .01), and non-Enterobacteriaceae gram-negative rod species (P < .0025), whereas the BTA detected significantly more isolates of Streptococcus spp (P < .0025). Growth of S aureus (P < .0025), Enterococcus spp (P < .0025), and Streptococcus spp (P < .0075) was detected earlier by the BTA when laboratory coverage was available during the first shift only (7:30 AM to 4:00 PM), and additionally of Enterobacteriaceae (P < .0005) and other gram-negative rod species (P < .0001) if coverage was extended to 12:00 AM. Yeasts were detected more rapidly by the ISO (P < .0025). The ISO contamination rate (5.9%)was sis times that of the BTA. Taking into account its ability to rapidly detect most organisms, its automated and thus labor-saving features, and the minimal contamination rate associated with its use, the BTA appears to be a reliable alternative to the ISO as a blood culturing system, although improvement in detection of staphylococci and non-Enterobacteriaceae gram-negative rods would be desirable. RP Engler, HD (reprint author), NIH,DEPT CLIN PATHOL,MICROBIOL SERV,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 22 TC 10 Z9 10 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 1996 VL 105 IS 6 BP 774 EP 781 PG 8 WC Pathology SC Pathology GA UQ496 UT WOS:A1996UQ49600018 PM 8659454 ER PT J AU Roth, MJ Stern, JB Hijazi, Y Haupt, HM Kumar, A AF Roth, MJ Stern, JB Hijazi, Y Haupt, HM Kumar, A TI Oncocytic nodular hidradenoma SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE oncocytoma; kidradenoma; skin adnexal tumor AB Oncocytic neoplasms are most commonly of salivary, thyroid, parathyroid, and renal origin. Ocular adnexal tumors with oncocytosis have been reported. We report an unusual example of a skin adnexal tumor from the back. A tumor of uncertain duration was excised from a 54-year-old man. Light microscopy of hematoxylin and eosin-stained sections showed a large, fairly well-defined cystic nodular hidradenoma with areas infiltrated by numerous closely arranged, large, uniform, oval and polygonal cells with abundant intensely eosinophilic cytoplasm and small central, dark, round nuclei. No significant cellular atypia or mitotic figures were observed. The cytoplasm of these cells showed markedly positive immunostaining with monoclonal antimitochondrial antibodies, Electron microscopy demonstrated cytoplasm packed with mitochondria. Pure oncocytic tumors usually follow a benign clinical course. The focal presence of oncocytes in an otherwise histologically recognizable tumor apparently does not affect the prognosis, which in this case is the favorable outcome expected for a nodular hidradenoma. C1 SUBURBAN HOSP, BETHESDA, MD USA. DERMATOPATHOL CONSULTAT SERV, DAMASCUS, MD USA. PENN HOSP, PHILADELPHIA, PA 19107 USA. RP NCI, PATHOL LAB,DEPT CYTOPATHOL,NIH,BLDG 10,ROOM 2A33, 10 CTR DR, BETHESDA, MD 20892 USA. NR 7 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0193-1091 EI 1533-0311 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD JUN PY 1996 VL 18 IS 3 BP 314 EP 316 DI 10.1097/00000372-199606000-00013 PG 3 WC Dermatology SC Dermatology GA UU988 UT WOS:A1996UU98800013 PM 8806968 ER PT J AU Hanson, RL Knowler, WC AF Hanson, RL Knowler, WC TI Familial correlations between insulinemia and glycemia. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ 85014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 27 EP 27 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800026 ER PT J AU Roumain, J Hanson, RL Pettitt, DJ Narayan, KMV Knowler, VC AF Roumain, J Hanson, RL Pettitt, DJ Narayan, KMV Knowler, VC TI Effect of hypertension on mortality in Pima Indians. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ 85014. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 48 EP 48 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800048 ER PT J AU Coates, RJ Bowen, DJ Kristal, AR Feng, Z Oberman, A Hall, WD George, V Lewis, CE Kestin, M Clifford, CK Grizzle, JE AF Coates, RJ Bowen, DJ Kristal, AR Feng, Z Oberman, A Hall, WD George, V Lewis, CE Kestin, M Clifford, CK Grizzle, JE TI The women's health trial feasibility study in minority populations: Changes in dietary intakes. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 EMORY UNIV,ATLANTA,GA 30322. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV MIAMI,MIAMI,FL 33152. NCI,ROCKVILLE,MD. UNIV ALABAMA,BIRMINGHAM,AL. RI Kristal, Alan/A-8779-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 63 EP 63 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800062 ER PT J AU FagotCampagna, A Hanson, RL Nelson, RG Sievers, ML Pettitt, DJ Narayan, KMV Knowler, WC AF FagotCampagna, A Hanson, RL Nelson, RG Sievers, ML Pettitt, DJ Narayan, KMV Knowler, WC TI Serum cholesterol and mortality rates in a population with low lipid levels: A U-shaped association. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ 85014. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 73 EP 73 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800073 ER PT J AU Wright, DJ Burns, D Nourjah, P Korelitz, JJ Nugent, R AF Wright, DJ Burns, D Nourjah, P Korelitz, JJ Nugent, R TI Interpreting correlation between variables in longitudinal studies using multivariate repeated measures models. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 WESTAT CORP,ROCKVILLE,MD 20850. NICHHD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 92 EP 92 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800092 ER PT J AU Lawson, L Macaluso, M Carew, B Kelaghan, J AF Lawson, L Macaluso, M Carew, B Kelaghan, J TI Determinants of participation and retention in a prospective study of barrier contraception and STD prevention. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. NICHHD,BETHESDA,MD 20892. RI Macaluso, Maurizio/J-2076-2015 OI Macaluso, Maurizio/0000-0002-2977-9690 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 117 EP 117 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800117 ER PT J AU Bulterys, M Landesman, S Burns, D Rubinstein, A Goedert, J AF Bulterys, M Landesman, S Burns, D Rubinstein, A Goedert, J TI Injection drug use during pregnancy and vertical HIV-1 transmission: A report from the mothers and infants cohort study in New York. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 119 EP 119 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800118 ER PT J AU Longnecker, MP Bernstein, L PaganiniHill, A Enger, SM Ross, RK AF Longnecker, MP Bernstein, L PaganiniHill, A Enger, SM Ross, RK TI Risk factors for in situ breast cancer in Los Angeles County. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 129 EP 129 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800129 ER PT J AU Swanson, CA Coates, RJ Malone, KE Gammon, MD Schoenberg, JB Brogan, DR Potischman, NA Brinton, LA AF Swanson, CA Coates, RJ Malone, KE Gammon, MD Schoenberg, JB Brogan, DR Potischman, NA Brinton, LA TI Alcohol consumption and breast cancer risk among women under age 45. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. EMORY UNIV,DEPT EPIDEMIOL,ATLANTA,GA 30322. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 132 EP 132 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800132 ER PT J AU Weiss, H Potischman, N Brinton, L AF Weiss, H Potischman, N Brinton, L TI Prenatal and perinatal risk factors for breast cancer in young women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 136 EP 136 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800136 ER PT J AU Ziegler, R Colavito, E Hartge, P McAdams, M Schoenberg, J Mason, T Fraumeni, J AF Ziegler, R Colavito, E Hartge, P McAdams, M Schoenberg, J Mason, T Fraumeni, J TI The importance of alpha-carotene, beta-carotene, and other phytochemicals in the etiology of lung cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 139 EP 139 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800138 ER PT J AU Meltzer, AA Everhart, JE AF Meltzer, AA Everhart, JE TI The association between diabetes and elevated serum aminotransferase activity among Mexican Americans. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 SOCIAL & SCI SYST INC,BETHESDA,MD 20814. NIDDKD,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 158 EP 158 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800159 ER PT J AU Sinks, T Henderson, A Blair, A Brown, D Staehling, N Humphrey, H AF Sinks, T Henderson, A Blair, A Brown, D Staehling, N Humphrey, H TI The mortality experience of people exposed to polybrominated biphenyls. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NIEHS,NCI,BETHESDA,MD. MICHIGAN DEPT PUBL HLTH,LANSING,MI 48909. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 172 EP 172 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800172 ER PT J AU Robin, RW Chester, B Rasmussen, JK Jaranson, J Goldman, D AF Robin, RW Chester, B Rasmussen, JK Jaranson, J Goldman, D TI Childhood sexual abuse and associated psychiatric disorders in a southwestern American Indian tribal SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 223 EP 223 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800221 ER PT J AU Rockhill, B Newman, B Moorman, P Millikan, R Weinberg, C AF Rockhill, B Newman, B Moorman, P Millikan, R Weinberg, C TI Summary attributable fraction and breast cancer risk factors. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 229 EP 229 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800227 ER PT J AU Freedman, AN Michalek, AM Caporaso, NE Weiss, HA Zhang, ZE Marshall, JR Mettlin, CJ Asirwatham, JE Petrelli, NJ AF Freedman, AN Michalek, AM Caporaso, NE Weiss, HA Zhang, ZE Marshall, JR Mettlin, CJ Asirwatham, JE Petrelli, NJ TI Aspirin use and p53 protein overexpression in colorectal cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 239 EP 239 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800236 ER PT J AU Macaluso, M Carew, B Artz, L Fleenor, M Robey, L Austin, H Hook, E Kelaghan, J AF Macaluso, M Carew, B Artz, L Fleenor, M Robey, L Austin, H Hook, E Kelaghan, J TI A study of the prophylactic efficacy of the female condom among high risk women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL. EMORY UNIV,ATLANTA,GA 30322. NICHHD,BETHESDA,MD 20892. RI Macaluso, Maurizio/J-2076-2015 OI Macaluso, Maurizio/0000-0002-2977-9690 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 311 EP 311 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800307 ER PT J AU Troisi, RJ Potischman, NA Brinton, LA Hoover, RN AF Troisi, RJ Potischman, NA Brinton, LA Hoover, RN TI C-peptide levels and risk of endometrial cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 329 EP 329 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800325 ER PT J AU Cooper, L Schreiner, P Smith, D Thompson, K AF Cooper, L Schreiner, P Smith, D Thompson, K TI Relationship of self image to body size and weight loss attempts in black women: The cardia study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 337 EP 337 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800333 ER PT J AU Ji, BT Shu, XO Linet, MS Zheng, W Ying, DM Jin, F AF Ji, BT Shu, XO Linet, MS Zheng, W Ying, DM Jin, F TI Paternal pre-conception cigarette smoking and the risk of childhood cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. SHANGHAI CANC INST,SHANGHAI,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 344 EP 344 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800340 ER PT J AU Potischman, N Weiss, HA Brinton, LA Coates, RJ Daling, JR Schoenberg, JB AF Potischman, N Weiss, HA Brinton, LA Coates, RJ Daling, JR Schoenberg, JB TI Adolescent diet and risk of breast cancer among young women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 SU S BP 347 EP 347 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN208 UT WOS:A1996UN20800342 ER PT J AU Bovill, EG Bild, DE Heiss, G Kuller, LH Lee, MH Rock, R Wahl, PW AF Bovill, EG Bild, DE Heiss, G Kuller, LH Lee, MH Rock, R Wahl, PW TI White blood cell counts in persons aged 65 years or more from the cardiovascular health study - Correlations with baseline clinical and demographic characteristics SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; blood cells; cardiovascular diseases; leukocyte count; risk factors ID CORONARY HEART-DISEASE; LEUKOCYTE COUNT; MYOCARDIAL-INFARCTION; RISK-FACTORS; ATHEROSCLEROSIS; SMOKING; PLASMA; PATHOGENESIS; CHOLESTEROL; COAGULATION AB A higher white blood cell (WBC) count has been shown to be a risk factor for myocardial infarction and stroke in middle-aged populations. This study evaluated the relation between baseline WBC count and other risk factors, as well as subclinical and prevalent disease, in the Cardiovascular Health Study, an epidemiologic study of coronary heart disease and stroke in 5,201 persons aged 65 years or older, Baseline data were collected over a 12-month period in 1989-1990. WBC counts were statistically significantly higher in people with prevalent and subclinical atherosclerotic cardiovascular disease than in those who were free of disease. WBC counts correlated (p < 0.01) positively with coagulation factors, measures of glucose metabolism, creatinine, smoking, and triglycerides. In contrast, WBC counts correlated negatively with high density lipoprotein cholesterol, forced expiratory volume, forced vital capacity, and height. The correlations between WBC counts and risk factors were similar in both the entire cohort and the subgroup of persons who had never smoked. The authors conclude that WBC counts in the elderly are associated with prevalent and subclinical atherosclerotic cardiovascular disease, as well as its risk factors. C1 NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. UNIV CALIF DAVIS,SCH MED,SACRAMENTO,CA 95817. AMER SOC CLIN PATHOLOGISTS,CHICAGO,IL. UNIV WASHINGTON,SCH PUBL HLTH,CARDIOVASC HLTH STUDY,SEATTLE,WA 98195. RP Bovill, EG (reprint author), UNIV VERMONT,COLL MED,DEPT PATHOL,BURLINGTON,VT 05405, USA. FU PHS HHS [N01-85081, N01-85080, N01-85079] NR 39 TC 53 Z9 54 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 BP 1107 EP 1115 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UM579 UT WOS:A1996UM57900005 PM 8633599 ER PT J AU Wacholder, S Hartge, P Armstrong, B AF Wacholder, S Hartge, P Armstrong, B TI Validation studies using an alloyed gold standard - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 UNIV LONDON LONDON SCH HYG & TROP MED,LONDON WC1E 7HT,ENGLAND. RP Wacholder, S (reprint author), NCI,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1996 VL 143 IS 11 BP 1176 EP 1176 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UM579 UT WOS:A1996UM57900017 ER PT J AU Jensen, RT AF Jensen, RT TI Should the 1996 citation for Zollinger-Ellison syndrome read: ''Acid-reducing surgery in, aggressive resection out''? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID GASTRIC HYPERSECRETORY STATES; DUODENAL GASTRINOMAS; OMEPRAZOLE; MANAGEMENT; THERAPY; TUMORS C1 NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NR 43 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 1996 VL 91 IS 6 BP 1067 EP 1070 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UP420 UT WOS:A1996UP42000001 PM 8651148 ER PT J AU Cantillon, M Brunswick, R Molina, D Bahro, M AF Cantillon, M Brunswick, R Molina, D Bahro, M TI Buspirone vs haloperidol - A double-blind trial for agitation in a nursing home population with Alzheimer's disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 8th Annual Meeting and Symposium of the American-Association-for-Geriatric-Psychiatry CY FEB 17-20, 1995 CL CANCUN, MEXICO SP Amer Assoc Geriatr Psychiat ID DEMENTIA; NEUROLEPTICS; PSYCHOSIS AB The authors report on a pilot double-blind comparison of buspirone with haloperidol in the treatment of agitation manifested by physical tension and motor activity in Alzheimer's disease (AD). A group of 26 nursing home residents underwent a 10-week comparison of 15 mg buspirone (n = 12) vs. 1.5 mg haloperidol (n = 14) per day. Tension and anxiety decreased to a greater extent in those patients who were treated with buspirone. Although it is not possible to draw definitive conclusions from a treatment study that does not include a placebo group, these findings suggest the potential value of further clinical research on buspirone in managing agitation in AD. C1 NIMH,SECT GERIATR PSYCHIAT,CLIN SCI LAB,BETHESDA,MD 20892. NR 30 TC 36 Z9 36 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SUM PY 1996 VL 4 IS 3 BP 263 EP 267 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA UX553 UT WOS:A1996UX55300011 ER PT J AU Meyer, CC Calis, KA AF Meyer, CC Calis, KA TI More information on vancomyin clearance by new hemodialysis membranes SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter C1 NIH,WARREN G MAGNUSON CLIN CTR,DRUG INFORMAT SERV,BETHESDA,MD 20892. RP Meyer, CC (reprint author), UNIV MISSOURI,SCH PHARM,KANSAS CITY,MO 64108, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUN 1 PY 1996 VL 53 IS 11 BP 1340 EP & PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UP698 UT WOS:A1996UP69800017 ER PT J AU Boissy, RE Zhao, HQ Oetting, WS Austin, LM Wildenberg, SC Boissy, YL Zhao, Y Sturm, RA Hearing, VJ King, RA Nordlund, JJ AF Boissy, RE Zhao, HQ Oetting, WS Austin, LM Wildenberg, SC Boissy, YL Zhao, Y Sturm, RA Hearing, VJ King, RA Nordlund, JJ TI Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: A new subtype of albinism classified as ''OCA3'' SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE BASE INSERTION; MESSENGER-RNA LEVELS; DOPACHROME TAUTOMERASE; B-LOCUS; MOUSE; GENE; CDNA; IDENTIFICATION; PIGMENTATION; MAPS AB Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci, Melanocytes were cultured from an African-American with OCA, who exhibited the phenotype of Brown OCA, and his normal fraternal twin. Melanocytes cultured from the patient with OCA and the normal twin appeared brown versus black, respectively. Melanocytes from both the patient with OCA and the normal twin demonstrated equal amounts of NP-40-soluble melanin; however, melanocytes from the patient with OCA contained only 7% of the amount of insoluble melanin found from the normal twin. Tyrosinase-related protein-1 (TRP-1) was not detected in the OCA melanocytes by use of various anti-TRP-l probes. Furthermore, transcripts for TRP-1 were absent in cultured OCA melanocytes. The affected twin was homozygous for a single-bp deletion in exon 6, removing an A in codon 368 and leading to a premature stop at codon 384. Tyrosine hydroxylase activity of the OCA melanocytes was comparable to controls when assayed in cell lysates but was only 30% of controls when assayed in intact cells. We conclude that this mutation of the human TRP-1 gene affects its interaction with tyrosinase, resulting in dysregulation of tyrosinase activity, promotes the synthesis of brown versus black melanin, and is responsible for a third genetic type of OCA in humans, which we classify as ''OCA3.'' C1 UNIV MINNESOTA,SCH MED,DEPT MED & PEDIAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,INST HUMAN GENET,MINNEAPOLIS,MN 55455. UNIV QUEENSLAND,CTR MOL BIOL & CELLULAR BIOL,BRISBANE,QLD,AUSTRALIA. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Boissy, RE (reprint author), UNIV CINCINNATI,COLL MED,DEPT DERMATOL,POB 670592,CINCINNATI,OH 45267, USA. RI Sturm, Richard/C-9943-2009 OI Sturm, Richard/0000-0003-1301-0294 FU NIGMS NIH HHS [GM 22167] NR 68 TC 125 Z9 131 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1996 VL 58 IS 6 BP 1145 EP 1156 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA UM271 UT WOS:A1996UM27100007 PM 8651291 ER PT J AU DeteraWadleigh, SD Badner, JA Goldin, LR Berrettini, WH Sanders, AR Rollins, DY Turner, G Moses, T Haerian, H Muniec, D Nurnberger, JI Gershon, ES AF DeteraWadleigh, SD Badner, JA Goldin, LR Berrettini, WH Sanders, AR Rollins, DY Turner, G Moses, T Haerian, H Muniec, D Nurnberger, JI Gershon, ES TI Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MANIC-DEPRESSIVE ILLNESS; X-CHROMOSOME MARKERS; LINKAGE ANALYSIS; PEDIGREES; GENE; DISEASE AB In 22 multiplex pedigrees screened for linkage to bipolar disorder, by use of 18 markers on chromosome 21q, single-locus affected-sib-pair (ASP) analysis detected a high proportion (57%-62%) of alleles shared identical by descent (IBD), with P values of .049-.0008 on nine marker loci. Multilocus ASP analyses revealed locus trios in the distal region between D21S270 and D21S171, with excess allele sharing (nominal P values <.01) under two affection-status models, ASM I (bipolars and schizoaffectives) and ASM II (ASM I plus recurrent unipolars). In addition, under ASM I, the proximal interval spanned by D21S1436 and D21S65 showed locus trios with excess allele sharing (nominal P values of .03-.0003). These findings support prior evidence that a susceptibility locus for bipolar disorder is on 21q. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT & HUMAN BEHAV,PHILADELPHIA,PA 19107. INDIANA UNIV,INST PSYCHIAT RES,DEPT PSYCHIAT,INDIANAPOLIS,IN. RP DeteraWadleigh, SD (reprint author), NIMH,UNIT GENE MAPPING & EXPRESS,CLIN NEUROGENET BRANCH,NIH,BLDG 10,ROOM 3N218,BETHESDA,MD 20892, USA. OI Nurnberger, John/0000-0002-7674-1767 NR 38 TC 110 Z9 111 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1996 VL 58 IS 6 BP 1279 EP 1285 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA UM271 UT WOS:A1996UM27100022 PM 8651306 ER PT J AU Gershon, ES Goldin, LR Badner, JA Berrettini, WH AF Gershon, ES Goldin, LR Badner, JA Berrettini, WH TI Detection of linkage to affective disorders in the catalogued Amish pedigrees: Reply SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. RP Gershon, ES (reprint author), NIMH,NIH,BETHESDA,MD 20892, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1996 VL 58 IS 6 BP 1381 EP 1384 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA UM271 UT WOS:A1996UM27100034 PM 8651318 ER PT J AU Pauls, DL Ott, J Paul, SM Allen, CR Fann, CSJ Carulli, JP Falls, KM Bouthillier, CA Gravius, TC Keith, TP Egeland, JA Ginns, EI AF Pauls, DL Ott, J Paul, SM Allen, CR Fann, CSJ Carulli, JP Falls, KM Bouthillier, CA Gravius, TC Keith, TP Egeland, JA Ginns, EI TI Chromosome 18 markers: Linked or not linked to bipolar affective disorders in the Old Order Amish? Reply SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 COLUMBIA UNIV,NEW YORK,NY. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY. NIMH,INTRAMURAL RES PROGRAM,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. LILLY RES LABS,INDIANAPOLIS,IN. UNIV MIAMI,DEPT PSYCHIAT,MIAMI,FL 33152. GENOME THERAPEUT CORP,WALTHAM,MA. RP Pauls, DL (reprint author), YALE UNIV,SCH MED,CTR CHILD STUDY,230 S FRONTAGE RD,POB 207900,NEW HAVEN,CT 06520, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1996 VL 58 IS 6 BP 1384 EP 1385 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UM271 UT WOS:A1996UM27100035 ER EF