FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Giese, NA Gazzinelli, RT Morawetz, RA Morse, HC AF Giese, NA Gazzinelli, RT Morawetz, RA Morse, HC TI Role of IL12 in MAIDS SO RESEARCH IN IMMUNOLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MURINE AIDS; INFECTION; CELLS; ACTIVATION; EXPRESSION; INDUCTION; VIRUS; MOUSE; MICE C1 NIAID,NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP Giese, NA (reprint author), NIAID,NIH,IMMUNOPATHOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 20 TC 4 Z9 4 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP-OCT PY 1995 VL 146 IS 7-8 BP 600 EP 604 DI 10.1016/0923-2494(96)83037-9 PG 5 WC Immunology SC Immunology GA TW313 UT WOS:A1995TW31300103 PM 8839167 ER PT J AU Chougnet, C Clerici, M Shearer, GM AF Chougnet, C Clerici, M Shearer, GM TI Role of IL12 in HIV disease AIDS SO RESEARCH IN IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; INFECTION; CELLS; INTERLEUKIN-12; DEATH C1 UNIV MILAN,CATTEDRA IMMUNOL,I-20122 MILAN,ITALY. RP Chougnet, C (reprint author), NCI,NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 38 TC 16 Z9 16 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP-OCT PY 1995 VL 146 IS 7-8 BP 615 EP 619 DI 10.1016/0923-2494(96)83039-2 PG 5 WC Immunology SC Immunology GA TW313 UT WOS:A1995TW31300112 PM 8839169 ER PT J AU WALDER, R KALVATCHEV, Z TOBIN, GJ BARRIOS, MN GARZARO, DJ GONDA, MA AF WALDER, R KALVATCHEV, Z TOBIN, GJ BARRIOS, MN GARZARO, DJ GONDA, MA TI POSSIBLE ROLE OF BOVINE IMMUNODEFICIENCY VIRUS IN BOVINE PARAPLEGIC SYNDROME - EVIDENCE FROM IMMUNOCHEMICAL, VIROLOGICAL AND SEROPREVALENCE STUDIES SO RESEARCH IN VIROLOGY LA English DT Article DE BIV; RETROVIRIDAE; IMMUNODEFICIENCY; PARAPLEGIA; BOVINE; BPS; ANTIBODIES; IMMUNOBLOT ANALYSES; PATHOGENESIS ID MOLECULAR-CLONING; LEUKEMIA-VIRUS; VISNA VIRUS; INFECTION; CATTLE; HIV-1; PROTEINS; BINDING; RABBITS; CELLS AB Bovine paraplegic syndrome (BPS) is a debilitating cattle disease of unknown origin that is characterized by leukocytosis, lymphocytopenia tend monocytopenia. The major clinical signs are difficulties in locomotion affecting hind limbs, hypoalgesia in the hind quarters, posterior paralysis and death within 72 to 96 hours after recumbency. To investigate the aetiological basis of BPS, we examined a possible association of the syndrome with infection by bovine immunodeficiency virus (BIV), a lentivirus implicated in immune system dysfunction:and central nervous system lesions in cattle. Serum samples (n = 1, 278) were collected from both healthy and BPS-prevalent cattle herds in Venezuela, and organ extracts were prepared from euthanized animals (n = 11) suspected of having BPS. Sera were analysed for reactivity to recombinant BIV and bovine leukaemia virus gag precursor proteins by immunoblot procedures. Serum reactivity to BIV ranged from 12 to 66 % between groups of BPS prevalent herds. The percentage of samples reactive to BLV antigen was much lower (2 to 17 %). Rabbits inoculated with extracts from BPS-afflicted animals exhibited an anamnestic immune response to BIV antigens as well as the presence of BIV gag antigens in their tissues. We present evidence for a possible association between BPS disease and a viral agent related to BIV. The role of BIV, in combination with malnutrition, in BPS is discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,CELL & MOLEC STRUCT LAB,FREDERICK,MD. RP WALDER, R (reprint author), INST VENEZOLANO INVEST CIENT,CTR MICROBIOL & BIOL CELULAR,VIRUS ANIM LAB,APDO 21827,CARACAS,VENEZUELA. RI Garzaro R., Domingo/E-6221-2010 NR 25 TC 25 Z9 25 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD SEP-OCT PY 1995 VL 146 IS 5 BP 313 EP 323 DI 10.1016/0923-2516(96)80594-2 PG 11 WC Virology SC Virology GA TB890 UT WOS:A1995TB89000001 PM 8578005 ER PT J AU MCKENZIE, TL FELDMAN, H WOODS, SE ROMERO, KA DAHLSTROM, V STONE, EJ STRIKMILLER, PK WILLISTON, JM HARSHA, DW AF MCKENZIE, TL FELDMAN, H WOODS, SE ROMERO, KA DAHLSTROM, V STONE, EJ STRIKMILLER, PK WILLISTON, JM HARSHA, DW TI CHILDREN ACTIVITY LEVELS AND LESSON CONTEXT DURING 3RD-GRADE PHYSICAL-EDUCATION SO RESEARCH QUARTERLY FOR EXERCISE AND SPORT LA English DT Article DE CHILDREN; PHYSICAL ACTIVITY; PHYSICAL EDUCATION; HEALTH ID PROGRAM; CURRICULUM; HEALTH AB Little is known about children's activity levels during physical education classes and how they relate to the national health objectives for the year 2000 (U.S. Public Health Service, 1991). We systemically observed students' physical activity and associated variables in 293 third-grade physical education lessons in 95 schools in 4 Child and Adolescent Trial for Cardiovascular Health (CATCH) centers in California, Louisiana, Minnesota, and Texas. The influence of independent variables was assessed simultaneously by analysis of variance. Significant differences among study centers were evidenced for both physical activity and lesson context variables. Additionally, there were differences among variables for lesson location and teacher specialty, but not for teacher gender. Boys were more active than girls, but only free play opportunities. The findings have widespread implications for educators responsible for developing and implementing health-related physical education programs, as well as for designing and conduction staff development. C1 UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NEW ENGLAND RES INST,BOSTON,MA. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. TULANE SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. RP MCKENZIE, TL (reprint author), SAN DIEGO STATE UNIV,DEPT EXERCISE & NUTR SCI,SAN DIEGO,CA 92182, USA. FU NHLBI NIH HHS [UO1-HL-39852, UO1-HL-39870, UO1-HL-39906] NR 25 TC 126 Z9 127 U1 0 U2 5 PU AMER ALLIANCE HEALTH PHYS EDUC REC & DANCE PI RESTON PA 1900 ASSOCIATION DRIVE, RESTON, VA 22091 SN 0270-1367 J9 RES Q EXERCISE SPORT JI Res. Q. Exerc. Sport PD SEP PY 1995 VL 66 IS 3 BP 184 EP 193 PG 10 WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology; Sport Sciences SC Social Sciences - Other Topics; Psychology; Sport Sciences GA RQ242 UT WOS:A1995RQ24200003 PM 7481079 ER PT J AU MAKINO, M MURPHY, DB MELVOLD, RW HARTLEY, JW MORSE, HC AF MAKINO, M MURPHY, DB MELVOLD, RW HARTLEY, JW MORSE, HC TI IMPACT OF MHC CLASS-I GENE ON RESISTANCE TO MURINE AIDS SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; LEUKEMIA VIRUSES; MICE; SUSCEPTIBILITY; MAIDS; MOUSE; H-2; EXPRESSION; INDUCTION; STRAINS AB Development of murine AIDS in mice following infection with LP-BM5 murine leukaemia virus (MuLV) is highly strain dependent, with strain differences determind by genes within and outside H-2. Among H-2 genes, the D-d gene is the most closely associated with resistance to LP-BMS MuLV infection. However, the D-d-mediated resistance is highly influenced by outside H-2 genes, i.e. A lineage strains are more resistant than mice strains of B6/B10 lineage. In this study, the mice having BALB background were analysed and, similarly to A lineage mice, only D-d gene products were found to be required to provide resistance to LP-BMS MuLV infection, Furthermore, BALB/c Kh mice bearing both D-d and L(d) genes clearly showed obviously higher resistance than BALB/c-H-2(dm2) mice solely having the D-d gene, In addition, in the long-term observation of the effect of the D-d gene on B6/B10 background mice, D8 mice having the D-d gene as a transgene and expressing a high level D-d gene product showed higher resistance than naturally recombinant B10.A(18R) mice. These results suggest that the MAIDS resistance associated with the D end loci is dependent on the level of expression of an MHC class I gene. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,CHICAGO,IL 60611. NEW YORK STATE DEPT HLTH,WADSWORTH CTR,ALBANY,NY 12201. RP MAKINO, M (reprint author), KAGOSHIMA UNIV,FAC MED,CTR CHRON VIRAL DIS,DIV HUMAN RETROVIRUSES,8-35-1 SAKURAGAOKA,KAGOSHIMA 890,JAPAN. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [AI-14349-14, AI-16919, N0-AI-72622] NR 26 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD SEP PY 1995 VL 42 IS 3 BP 368 EP 372 DI 10.1111/j.1365-3083.1995.tb03669.x PG 5 WC Immunology SC Immunology GA RR540 UT WOS:A1995RR54000012 PM 7660069 ER PT J AU GOLD, JM BLAXTON, TA HERMANN, BP RANDOLPH, C FEDIO, P GOLDBERG, TE THEODORE, WH WEINBERGER, DR AF GOLD, JM BLAXTON, TA HERMANN, BP RANDOLPH, C FEDIO, P GOLDBERG, TE THEODORE, WH WEINBERGER, DR TI MEMORY AND INTELLIGENCE IN LATERALIZED TEMPORAL-LOBE EPILEPSY AND SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MEMORY; INTELLIGENCE; TEMPORAL LOBE EPILEPSY; (SCHIZOPHRENIA) ID MONOZYGOTIC TWINS DISCORDANT; PSYCHOSIS AB Recent neuroimaging studies of patients with schizophrenia have suggested structural and functional abnormalities of mesial temporal lobe structures. We compared the intelligence and memory test performance of 70 patients with schizophrenia and 72 patients with focal, lateralized temporal lobe epilepsy (30 left, 42 right temporal lobe) in order to examine the adequacy of a temporal lobe model of schizophrenic cognitive deficits. The groups did not differ in age, education, or Full Scale IQ. The right temporal lobe group had better overall memory performance than either the left temporal or schizophrenic patients. Unlike the schizophrenic patients, the memory impairment of the left temporal group was most evident with verbal materials and was amplified by delayed testing. Both epilepsy groups had better visual memory than the schizophrenic group. The clear differences in performance pattern between groups suggests that lateralized temporal lobe dysfunction does not by itself provide an adequate model of schizophrenic cognitive impairment. C1 NINCDS,EPILEPSY RES BRANCH,DIRP,WASHINGTON,DC 20032. BAPTIST MEM HOSP,CTR EPICARE,WASHINGTON,DC 20032. NINCDS,EXPTL THERAPEUT BRANCH,WASHINGTON,DC 20032. NIMH,DIRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP GOLD, JM (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN & RES SERV BRANCH,DIRP,2700 MARTIN LUTHER KING AVE SE,WASHINGTON,DC 20032, USA. NR 26 TC 26 Z9 26 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 1995 VL 17 IS 1 BP 59 EP 65 DI 10.1016/0920-9964(95)00030-P PG 7 WC Psychiatry SC Psychiatry GA RY300 UT WOS:A1995RY30000007 PM 8541251 ER PT J AU GOLDBERG, TE TORREY, EF GOLD, JM BIGELOW, LB RAGLAND, RD TAYLOR, E WEINBERGER, DR AF GOLDBERG, TE TORREY, EF GOLD, JM BIGELOW, LB RAGLAND, RD TAYLOR, E WEINBERGER, DR TI GENETIC RISK OF NEUROPSYCHOLOGICAL IMPAIRMENT IN SCHIZOPHRENIA - A STUDY OF MONOZYGOTIC TWINS DISCORDANT AND CONCORDANT FOR THE DISORDER SO SCHIZOPHRENIA RESEARCH LA English DT Article DE GENETIC RISK; MONOZYGOTIC TWINS; NEUROPSYCHOLOGICAL IMPAIRMENT; (SCHIZOPHRENIA) ID CARD SORTING TEST; SIBLINGS; SIGNS AB We used a paradigm involving monozygotic (MZ) twin pairs discordant for schizophrenia (n=20) and concordant for schizophrenia (n=8), as well as normal MZ twin pairs (n=7) in order to study cognitive measures of genetic risk in schizophrenia. A comparison between the unaffected twins from the discordant sample and the normal twins indicated subtle attenuations in some aspects of memory and executive functioning in the unaffected group and thus provided evidence for cognitive markers of a genetic component in schizophrenia. A comparison of the affected twins from the discordant pairs and the concordant twins yielded virtually no differences, suggesting that a distinction between familial and sporadic cases is not valid in this sample. Large differences between unaffected and affected members of discordant pairs on a wide variety of variables, including IQ, attention, memory, and executive function, highlighted the magnitude of disease-specific factors. RP GOLDBERG, TE (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 25 TC 119 Z9 123 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 1995 VL 17 IS 1 BP 77 EP 84 DI 10.1016/0920-9964(95)00032-H PG 8 WC Psychiatry SC Psychiatry GA RY300 UT WOS:A1995RY30000009 PM 8541253 ER PT J AU ALEXANDER, NJ AF ALEXANDER, NJ TI FUTURE CONTRACEPTIVES SO SCIENTIFIC AMERICAN LA English DT Article C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. WHO,COMM TASK FORCE METHODS REGULAT MALE FERTIL,GENEVA,SWITZERLAND. RP ALEXANDER, NJ (reprint author), NICHHD,POPULAT RES CTR,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892, USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD SEP PY 1995 VL 273 IS 3 BP 136 EP 141 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP670 UT WOS:A1995RP67000040 PM 7652531 ER PT J AU MIZEJEWSKI, GJ MORRIS, JE HAUSER, P WEINTRAUB, BD PASS, KA AF MIZEJEWSKI, GJ MORRIS, JE HAUSER, P WEINTRAUB, BD PASS, KA TI A STRATEGY FOR NEWBORN SCREENING FOR RESISTANCE TO THYROID-HORMONE - POSSIBLE RELEVANCE TO ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO SCREENING LA English DT Article DE NEWBORN SCREENING; ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD); RESISTANCE TO THYROID HORMONE (RTH); THYROID; AUTOSOMAL DISEASE ID GENERALIZED RESISTANCE; LIGAND-BINDING; RECEPTOR-BETA; MUTATION; GENE; KINDREDS; FAMILIES; DOMAIN AB Introduction: Resistance to thyroid hormone (RTH) is an autosomal disease characterized by pituitary and peripheral tissue insensitivity to thyroid hormone, exemplified by elevated serum total and free thyroxine (TT4, FT4) concentrations coincident with inappropriate levels of thyroid stimulating hormone (TSH). The most common clinical manifestation of RTH is attention deficit hyperactivity disorder, a behavioral disorder affecting 3%-5% of the school age population. Methods: Utilizing the New York State newborn screening hypothyroid program, an anonymous study was performed on 600 filter paper blood specimens exceeding the 99th percentile of TT4 values in each day's assays. This upper first percentile of TT4 specimens was assayed for TSH and FT4 from the same newborn specimen; controls consisted of age-matched specimens with TT4 values at the 50th percentile, Results: The population mean for TT4 was expectedly elevated in the test group; while TSH and FT4 values were similar in both groups, Fourteen specimens displayed both elevated FT4 and elevated TT4 levels. Seven of these 14 specimens demonstrated inappropriate TSH levels, suggestive of RTH. Discussion: This anonymous study suggests that it may be feasible to identify newborns presumptively positive for RTH from screening specimens. Identification would be based on elevated TT4, elevated FT4 and inappropriately normal or elevated TSH. Studies to identify mutations in PCR-amplified thyroid receptor DNA from these newborn specimens, as a means of determining whether they represent infants with RTH, are in progress. C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,NEWBORN SCREENING LAB,ALBANY,NY 12201. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,GENET SERV,ALBANY,NY 12201. UNIV MARYLAND,MED CTR,DEPT PSYCHIAT,BALTIMORE,MD 21201. BALTIMORE VET ADM MED CTR,PSYCHIAT SERV,BALTIMORE,MD 21201. NIDDKD,MCEB,BETHESDA,MD 20892. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-6164 J9 SCREENING JI Screening PD SEP PY 1995 VL 4 IS 2 BP 61 EP 70 DI 10.1016/0925-6164(95)00104-T PG 10 WC Medical Laboratory Technology; Pediatrics SC Medical Laboratory Technology; Pediatrics GA RX710 UT WOS:A1995RX71000001 ER PT J AU BEEKMANN, SE HENDERSON, DK AF BEEKMANN, SE HENDERSON, DK TI HIV-INFECTION IN HEALTH-CARE WORKERS - RISK FOR INFECTION AND METHODS OF PREVENTION SO SEMINARS IN DERMATOLOGY LA English DT Article RP BEEKMANN, SE (reprint author), NIH,HOSP EPIDEMIOL SERV,BLDG 10,ROOM 4A21,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-145X J9 SEMIN DERMATOL JI Semin. Dermatol. PD SEP PY 1995 VL 14 IS 3 BP 212 EP 218 PG 7 WC Dermatology SC Dermatology GA RT061 UT WOS:A1995RT06100005 PM 7488537 ER PT J AU LAKS, MM BERSON, A AF LAKS, MM BERSON, A TI ELECTRICAL SAFETY MEASURES FOR PHYSICIANS USING ELECTROMEDICAL EQUIPMENT SO SEMINARS IN NEUROLOGY LA English DT Article ID VENTRICULAR-FIBRILLATION C1 NHLBI,BETHESDA,MD 20892. RP LAKS, MM (reprint author), UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,1000 W CARSON ST,TORRANCE,CA 90502, USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD SEP PY 1995 VL 15 IS 3 BP 311 EP 316 DI 10.1055/s-2008-1041037 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RY294 UT WOS:A1995RY29400013 PM 8570934 ER PT J AU PASS, HI DONINGTON, JS AF PASS, HI DONINGTON, JS TI USE OF PHOTODYNAMIC THERAPY FOR THE MANAGEMENT OF PLEURAL MALIGNANCIES SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE PHOTOTHERAPY; MESOTHELIOMA; LASER; PORPHYRIN; PLEURA; DEBULKING AB Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention being investigated for oncologic therapy. Surfaces such as the pleura or the peritoneum are frequently involved with primary or metastatic cancer, and the chance for cure in such situations is low due to the inability to eradicate all the disease. A series of investigations have been performed at the National Cancer Institute since 1985 studying the possible use of PDT for large cavity treatment. This report details evolution of the methodology, toxicity, and overall feasibility of the delivery of intrapleural PDT to patients after debulking of primary and malignant chest neoplasms, with an emphasis on malignant pleural mesothelioma. These investigations have culminated in an ongoing Phase III trial to define the efficacy of intrapleural PDT. (C) 1995 Wiley-Liss, Inc. RP PASS, HI (reprint author), NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 0 TC 16 Z9 16 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD SEP-OCT PY 1995 VL 11 IS 5 BP 360 EP 367 DI 10.1002/ssu.2980110506 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA RL872 UT WOS:A1995RL87200005 PM 7569558 ER PT J AU GREENLUND, KJ LIU, K KNOX, S MCCREATH, H DYER, AR GARDIN, J AF GREENLUND, KJ LIU, K KNOX, S MCCREATH, H DYER, AR GARDIN, J TI PSYCHOSOCIAL WORK CHARACTERISTICS AND CARDIOVASCULAR-DISEASE RISK-FACTORS IN YOUNG-ADULTS - THE CARDIA STUDY SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE JOB STRAIN; JOB DEMANDS; DECISION LATITUDE; CARDIOVASCULAR DISEASE RISK FACTORS ID CORONARY HEART-DISEASE; DIASTOLIC BLOOD-PRESSURE; JOB DECISION LATITUDE; MYOCARDIAL-INFARCTION; OCCUPATIONAL STRESS; STRAIN; HEALTH; MEN; PREVALENCE; DEMANDS AB The associations of high job demands, low decision latitude and job strain with cardiovascular disease (CVD) risk factors among 2655 black and white working men and women were examined in the Coronary Artery Risk Development in Young Adults study-a large, prospective, multi-center study of the development of CVD risk factors in young adults aged 18-30 years at baseline (1985-1986). Multiple linear and multiple logistic regression were used in cross-sectional analyses to examine the associations of job demands, decision latitude and job strain with blood pressure, total serum cholesterol, alcohol use and cigarette consumption. Inverse associations with risk factors were found for high job demands, low decision latitude and job strain. Few associations supported the hypotheses that high job demands, low decision latitude or job strain are associated with increased levels of CVD risk factors. We discuss possible explanations for these findings, including methodologic, age and gender differences between studies. In addition, we discuss the validity of job strain measures for women and minority workers. C1 NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL 60611. NHLBI,BETHESDA,MD 20892. UNIV ALABAMA,CARDIA COORDINATING CTR,BIRMINGHAM,AL. UNIV CALIF IRVINE,CTR ECHOCARDIOG READING,ORANGE,CA 92668. FU NHLBI NIH HHS [N01-HC-48049, N01-HC-48048, N01-HC-48047] NR 47 TC 54 Z9 55 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD SEP PY 1995 VL 41 IS 5 BP 717 EP 723 DI 10.1016/0277-9536(94)00385-7 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA RQ627 UT WOS:A1995RQ62700011 PM 7502103 ER PT J AU FALCK, RS ASHERY, RS CARLSON, RG WANG, JC SIEGAL, HA AF FALCK, RS ASHERY, RS CARLSON, RG WANG, JC SIEGAL, HA TI INJECTION-DRUG USERS, CRACK SMOKERS, AND THE USE OF HUMAN-SERVICES SO SOCIAL WORK RESEARCH LA English DT Article DE DRUG ABUSE; SOCIAL SERVICES; UTILIZATION ID GENDER DIFFERENCES; HEALTH-SERVICES; URBAN HOMELESS; MENTAL-HEALTH; HELP-SEEKING; AMERICANS; BEHAVIOR; ILLNESS; BLACK; WOMEN AB This article describes the use of human services by 245 injection drug users and 125 track cocaine smokers living in Columbus and Dayton, Ohio. These so-called hard drug users were asked about their current involvement with six categories of human services-homeless shelters, food pantries or soup kitchens, medical services, government financial assistance, drug self-help groups, and miscellaneous services. The findings suggest that drug users are active consumers of human services; nearly 90 percent reported current involvement. The average number of services used was more than three per person. Results of multivariate analyses suggest that a host of variables influence the type and number of services used. The study found no gross patterns of discrimination. It is concluded that more information is needed about how hard drug users interact with the human services system and that expectations of what the human services system is capable of accomplishing need to be re-evaluated. C1 NIDA,ROCKVILLE,MD. RP FALCK, RS (reprint author), WRIGHT STATE UNIV,SCH MED,AIDS PREVENT RES PROJECT,143 BIOL SCI BLDG,DAYTON,OH 45435, USA. FU NIDA NIH HHS [U01 DA07305] NR 52 TC 5 Z9 5 U1 2 U2 3 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 SN 1070-5309 J9 SOC WORK RES JI Soc. Work Res. PD SEP PY 1995 VL 19 IS 3 BP 164 EP 173 PG 10 WC Social Work SC Social Work GA RQ056 UT WOS:A1995RQ05600004 PM 10144839 ER PT J AU Ho, PP Couch, FJ Brody, LC Abel, KJ Boehnke, M Shearon, TH Chandrasekharappa, SC Collins, FS Weber, BL AF Ho, PP Couch, FJ Brody, LC Abel, KJ Boehnke, M Shearon, TH Chandrasekharappa, SC Collins, FS Weber, BL TI Localization of the human homolog of the yeast cell division control 27 gene (CDC27) proximal to ITGB3 on human chromosome 17q21.3 SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID BRCA1 REGION; HYBRIDS AB The human homolog of the Saccharomyces cerevisiae cell division control 27 gene (CDC27) was mapped to human chromosome 17q12-q21 using a panel of human/rodent somatic cell hybrids and localized distal to the breast cancer susceptibility gene, BRCA1, using a panel of radiation hybrids. The radiation hybrid panel indicates that the most likely position of human CDC27 on human chromosome 17 is between the marker DI7S409 and the beta 3 subunit of integrin (ITGB3). Further confirmation of this localization comes from the sequence tagged site (STS) mapping of human CDC27 to the same yeast artificial chromosomes (YACs) positive for ITGB3. The estimated distance between ITGB3 and human CDC27 is less than 600 kb. C1 UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. NATL CTR HUMAN GENOME RES,NIH,LAB GENE TRANSFER,BETHESDA,MD 20892. MICROBIOL UNIT,DEPT HUMAN GENET,ANN ARBOR,MI 48109. MICROBIOL UNIT,DEPT BIOSTAT,ANN ARBOR,MI 48109. RP Ho, PP (reprint author), WAYNE STATE UNIV,DEPT IMMUNOL & MICROBIOL,540 E CANFIELD,DETROIT,MI 48201, USA. FU NCI NIH HHS [R01 CA57601, R01 CA61231]; NHGRI NIH HHS [R01 HG60209] NR 12 TC 2 Z9 2 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD SEP PY 1995 VL 21 IS 5 BP 351 EP 355 DI 10.1007/BF02257470 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA TY763 UT WOS:A1995TY76300007 PM 8619132 ER PT J AU MORSE, HC GIESE, N MORAWETZ, R TANG, Y GAZZINELLI, R KIM, WK CHATTOPADHYAY, S HARTLEY, JW AF MORSE, HC GIESE, N MORAWETZ, R TANG, Y GAZZINELLI, R KIM, WK CHATTOPADHYAY, S HARTLEY, JW TI CELLS AND CYTOKINES IN THE PATHOGENESIS OF MAIDS, A RETROVIRUS-INDUCED IMMUNODEFICIENCY SYNDROME OF MICE SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID CD4+ T-CELLS; MURINE AIDS VIRUS; MEDIATED-IMMUNITY; ANTIGEN RECEPTOR; HIGH EXPRESSION; IN-VIVO; SUPERANTIGEN; ACTIVATION; INDUCTION; PROGRESSION C1 NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. RP MORSE, HC (reprint author), NIAID, IMMUNOPATHOL LAB, 7 CTR DR, MSC 0760, BETHESDA, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 66 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD SEP PY 1995 VL 17 IS 2-3 BP 231 EP 245 PG 15 WC Immunology; Pathology SC Immunology; Pathology GA RZ167 UT WOS:A1995RZ16700008 PM 8571170 ER PT J AU LIN, HJ WOLF, PA BENJAMIN, EJ BELANGER, AJ DAGOSTINO, RB AF LIN, HJ WOLF, PA BENJAMIN, EJ BELANGER, AJ DAGOSTINO, RB TI NEWLY-DIAGNOSED ATRIAL-FIBRILLATION AND ACUTE STROKE - THE FRAMINGHAM-STUDY SO STROKE LA English DT Article DE ATRIAL FIBRILLATION; RISK FACTORS; STROKE ONSET ID CARDIAC-ARRHYTHMIAS; RISK-FACTORS; SUBARACHNOID HEMORRHAGE; COMPLICATIONS AB Background and Purpose When atrial fibrillation (AF) is first documented at the time of onset of acute stroke, it is difficult to establish a temporal relationship between AF and stroke. Did AF precede and precipitate the stroke, or did the arrhythmia appear as a result of stroke? Following the course of the newly diagnosed AF may help to clarify this relationship. Methods The Framingham Study cohort of 5070 members, aged 30 to 62 years and free of cardiovascular disease at entry, has been under surveillance for the development of cardiovascular disease, including stroke. We followed the course of AF, which was documented for the first time on or soon after hospital admission for stroke. Results During 38 years of follow-up, 115 of 656 initial stroke events occurred in association with AF: 89 had previously documented AF, 21 had AF discovered for the first time on admission for the stroke, and 5 were admitted with sinus rhythm but developed AF after admission. Of the 21 subjects with AF diagnosed on admission, in 12 (57%) AF persisted thereafter (chronic AF). Among the other 9 persons presenting with nonpersistent AF, paroxysms recurred in 3 (14%) and became chronic AF in 4 (19%). AF was transient and did not recur in only 2 persons (10%). Of the 5 subjects who developed AF after admission, AF was sustained from the initial diagnosis in 2 and recurred in paroxysms or became established as chronic in 3. Conclusions Ninety-two percent (24/26) of subjects presenting with newly discovered AF at the time of acute stroke continued to have this rhythm disturbance in a chronic or paroxysmal form. In only 2 subjects (8%) was the arrhythmia short-lived and nonrecurrent. These follow-up data suggest that in most instances AF was probably the precipitant rather than the consequence of stroke. C1 BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,BOSTON CITY HOSP,SCH MED,CARDIOL SECT,BOSTON,MA. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. NHLBI,FRAMINGHAM STUDY,FRAMINGHAM,MA. FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [2-RO1 NS-17950-13] NR 27 TC 86 Z9 88 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1995 VL 26 IS 9 BP 1527 EP 1530 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA RR826 UT WOS:A1995RR82600003 PM 7660392 ER PT J AU TAKAHASHI, H KIRSCH, JR HASHIMOTO, K LONDON, ED KOEHLER, RC TRAYSTMAN, RJ AF TAKAHASHI, H KIRSCH, JR HASHIMOTO, K LONDON, ED KOEHLER, RC TRAYSTMAN, RJ TI PPBP [4-PHENYL-1-(4-PHENYLBUTYL) PIPERIDINE], A POTENT SIGMA-RECEPTOR LIGAND, DECREASES BRAIN INJURY AFTER TRANSIENT FOCAL ISCHEMIA IN CATS SO STROKE LA English DT Article DE CEREBRAL BLOOD FLOW; MIDDLE CEREBRAL ARTERY OCCLUSION; SIGMA RECEPTOR; EVOKED POTENTIALS, SOMATOSENSORY; TRIPHENYLTETRAZOLIUM STAINING ID D-ASPARTATE RECEPTOR; CEREBRAL-ISCHEMIA; BLOOD-FLOW; GERBIL; IFENPRODIL; BINDING; RAT; SL-82.0715; SKF-10,047; EFFICACY AB Background and Purpose We tested the hypothesis that administration of 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), a potent sigma-receptor ligand, during transient focal ischemia would affect early postischemic brain injury. Methods Halothane-anesthetized cats underwent left middle cerebral artery occlusion for 90 minutes followed by 4 hours of reperfusion. Control cats received saline (n=10). Experimental cats (2 groups, n=10 per group) were treated with PPBP at a rate of 0.1 mu mol/kg per hour (PPBP-0.1) or administered 1 mu mol/kg per hour (PPBP-1) intravenously from 75 minutes after initiation of ischemia and continuing during the 4 hours of reperfusion. Results As measured by the microsphere method, blood flow to the ipsilateral caudate nucleus was decreased similarly in all groups during ischemia, Blood flow to the ipsilateral inferior temporal cortex was decreased during ischemia in all groups but was higher in cats subsequently treated with PPBP ar the highest dose, even before drug administration. There was no difference in blood flow to the ipsilateral caudate nucleus or inferior temporal cortex (area of greatest cortical injury) during reperfusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral hemisphere (control, 29+/-5%; PPBP-0.1, 171+/-3%; PPBP-1, 6+/-1% of ipsilateral hemisphere; meant-SEM) and caudate nucleus (control, 49+/-5%; PPBP-0.1, 39+/-6%; PPBP-1, 25+/-5% of ipsilateral caudate nucleus) was less in cats treated with 1 mu mol/kg per hour of PPBP compared with cats treated with saline. Cats treated with 0.1 mu mol/kg per hour had a 45% smaller hemispheric injury volume than the control group without differences in intraischemic blood flow. Recovery of somatosensory evoked potential amplitude was greater in cats treated with PPBP-1 compared with control (control, 18+/-11%; PPBP-0.1, 30+/-14%; PPBP-1, 54+/-14% of baseline). Conclusions These data indicate that sigma-receptors may play an important role in the mechanism of acute injury in both the cortex and the caudate nucleus after 90 minutes of transient focal ischemia in the cat. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, sigma-receptors may contribute to the progression of injury in ischemic border regions. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. NIDA,DIV INTRAMURAL RES,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD. FU NINDS NIH HHS [NS-20020] NR 32 TC 39 Z9 40 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1995 VL 26 IS 9 BP 1676 EP 1682 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA RR826 UT WOS:A1995RR82600037 PM 7544928 ER PT J AU ROTHMAN, RB XU, H WANG, JB PARTILLA, JS KAYAKIRI, H RICE, KC UHL, GR AF ROTHMAN, RB XU, H WANG, JB PARTILLA, JS KAYAKIRI, H RICE, KC UHL, GR TI LIGAND SELECTIVITY OF CLONED HUMAN AND RAT OPIOID-MU RECEPTORS SO SYNAPSE LA English DT Article DE OPIATE RECEPTORS; [I-125] IOXY-AGO; [H-3] DAMGO; CHO CELLS ID OPIATE RECEPTOR; EXPRESSION; ANTAGONIST; CLONING AB Opiate receptors play major roles in analgesic and euphoric effects of opiate drugs. Recent cloning of cDNAs encoding the rodent and human mu receptor revealed high homology between the predicted receptors but also some sequence differences. To determine if these sequence differences produced significant changes in ligand-selectivity profiles, we assessed these profiles in expressing COS and CHO cell lines using the agonist ligand [I-125]IOXY-AGO (6 beta-[(125)Iodo]-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinan). This Ligand's high specific activity (2,200 Ci/mmol) and high affinity for mu opioid receptors generated high signal-to-noise ratio binding. The resulting ligand-selectivity profiles of the human and rat mu receptors reveal modest differences in affinities for morphine and naloxone in COS cells but not CHO cells. Ligand-selectivity profiles of the rat and human mu, receptors were otherwise similar. Interesting differences between these data and data previously obtained with the peptide agonist [H-3]DAMGO suggest that the peptide and alkaloid agonists may label different domains of the mu receptor. (C) 1995 Wiley-Liss, Inc.(*) C1 NIDA,DIR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,IRP,OFF DIRECTOR,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. RP ROTHMAN, RB (reprint author), NIDA,DIR,CLIN PSYCHOPHARMACOL SECT,4940 EASTERN AVE,POB 5180,BALTIMORE,MD 21224, USA. NR 13 TC 20 Z9 21 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 SEP PY 1995 VL 21 IS 1 BP 60 EP 64 DI 10.1002/syn.890210109 PG 5 WC Neurosciences SC Neurosciences & Neurology GA RR822 UT WOS:A1995RR82200008 PM 8525463 ER PT J AU MARONPOT, RR DEVEREUX, TR HEGI, M FOLEY, JF KANNO, J WISEMAN, R ANDERSON, MW AF MARONPOT, RR DEVEREUX, TR HEGI, M FOLEY, JF KANNO, J WISEMAN, R ANDERSON, MW TI HEPATIC AND PULMONARY CARCINOGENICITY OF METHYLENE-CHLORIDE IN MICE - A SEARCH FOR MECHANISMS SO TOXICOLOGY LA English DT Article DE BIOLOGICALLY-BASED DOSE-RESPONSE MODELS; INHALATION EXPOSURE; RISK ASSESSMENT ID FEMALE B6C3F1 MICE; P53 GENE; INDUCED LUNG; TUMORS; METABOLISM; DICHLOROMETHANE; DIHALOMETHANES; FORMALDEHYDE; ACTIVATION; CARCINOMA AB An inhalation study utilizing over 1400 female B6C3F1 mice was undertaken to study mechanistic factors associated with liver and lung tumor induction following exposure to 2000 ppm of methylene chloride. Mice were exposed to methylene chloride (treated) or,chamber air (controls) 6 h per day, for varying durations up to 104 weeks. Several interim sacrifices and 'stop exposures' were included. Exposure to 2000 ppm methylene chloride caused an increase in liver and lung neoplasia in the absence of overt cytotoxicity. Measurement of replicative DNA synthesis done after 13, 26, 52 and 78 weeks of exposure showed a significant decrease in the hepatocyte labeling index at 13 weeks. Replicative DNA synthesis in pulmonary airways after 1 2, 3, 4, 13 and 26 weeks of exposure to methylene chloride was significantly lower than in air-exposed controls. Likewise, the increase in tumor induction in treated mice was not associated with increased replicative DNA synthesis in liver foci or in alveolar parenchyma. The frequency and pattern of H-ras gene activation were similar in control and methylene chloride-induced liver neoplasms. Similarly, the frequency and pattern of K-ras activation in lung neoplasms were not altered by exposure to methylene chloride. Early exposure to methylene chloride for only 26 weeks was sufficient to cause an increase in lung tumors by 2 years, suggesting that methylene chloride may cause early and persistent loss of growth control in lung cells. This implies that risk management strategies should be aimed at minimizing or eliminating exposure to methylene chloride. Liver neoplasms continued to increase in incidence and multiplicity as exposure continued, suggesting that methylene chloride-induced hepatocarcinogenesis is facilitated by continuing exposure to methylene chloride. Since methylene chloride is a more potent inducer of lung than liver neoplasia, it is recommended that health risk assessment be based on the lung data. While no novel molecular lesions have been found to explain the induction of lung and liver neoplasia in mice, ongoing studies may identify other molecular changes that are important in the genesis of these neoplasms. Hence, it may be necessary to revise risk assessment and management strategies in light of future research findings. C1 UNIV ZURICH, CH-8006 ZURICH, SWITZERLAND. TOKYO MED & DENT UNIV, TOKYO 113, JAPAN. ST MARYS HOSP, GRAND JCT, CO USA. RP MARONPOT, RR (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Hegi, Monika/O-4796-2015 OI Hegi, Monika/0000-0003-0855-6495 NR 20 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD SEP 1 PY 1995 VL 102 IS 1-2 BP 73 EP 81 DI 10.1016/0300-483X(95)03037-G PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TA562 UT WOS:A1995TA56200006 PM 7482563 ER PT J AU KOHN, MC AF KOHN, MC TI BIOCHEMICAL-MECHANISMS AND CANCER RISK ASSESSMENT MODELS FOR DIOXIN SO TOXICOLOGY LA English DT Article DE DOSIMETRY; HEPATOCARCOGENESIS; RECEPTOR ID DOSE-RESPONSE RELATIONSHIPS; EPIDERMAL GROWTH-FACTOR; RAT-LIVER; CELL-PROLIFERATION; TUMOR PROMOTION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; CARCINOGENESIS; HEPATOCARCINOGENESIS; 2-HYDROXYLASE; RECEPTOR AB Biologically realistic mechanistic models of carcinogenesis by TCDD are composed of equations representing biochemical events leading to altered expression of proteins involved in the response or equations representing the kinetics of proliferation of clones of mutant cells. A biochemically augmented physiological dosimetry model reproduces the observed altered expression of liver proteins in female rats exposed to dioxin. The model suggests that oxidation of estradiol to DNA reactive quinones or semiquinones by CYP1A2 protein induced by TCDD may contribute to an increased mutational rate. It suggests that TCDD-stimulated production of a peptide ligand of the epidermal growth factor (EGF) receptor and subsequent activation of the receptor's tyrosine kinase activity may increase the rate of proliferation of susceptible cells. These calculated quantities can serve as indices of toxicity and can be used to predict tumor incidence as a function of exposure. RP KOHN, MC (reprint author), NIEHS, QUANTITAT & COMPUTAT BIOL LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 31 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD SEP 1 PY 1995 VL 102 IS 1-2 BP 133 EP 138 DI 10.1016/0300-483X(95)03042-E PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TA562 UT WOS:A1995TA56200011 PM 7482548 ER PT J AU KAYAMA, F YOSHIDA, T ELWELL, MR LUSTER, MI AF KAYAMA, F YOSHIDA, T ELWELL, MR LUSTER, MI TI CADMIUM-INDUCED RENAL DAMAGE AND PROINFLAMMATORY CYTOKINES - POSSIBLE ROLE OF IL-6 IN TUBULAR EPITHELIAL-CELL REGENERATION SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN MESANGIAL CELLS; GENE-EXPRESSION; GROWTH-FACTOR; INTERLEUKIN-6; METALLOTHIONEIN; PATHOGENESIS; TOXICITY; INJURY; MICE AB Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity, Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity. (C) 1995 Academic Press, Inc. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. TOKAI UNIV,DEPT ENVIRONM MED,KANAGAWA,JAPAN. UNIV OCCUPAT & ENVIRONM HLTH MED,KITAKYUSHU,FUKUOKA,JAPAN. RP KAYAMA, F (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 45 Z9 47 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1995 VL 134 IS 1 BP 26 EP 34 DI 10.1006/taap.1995.1165 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RU763 UT WOS:A1995RU76300003 PM 7676455 ER PT J AU KU, WW WINE, RN CHAE, BY GHANAYEM, BI CHAPIN, RE AF KU, WW WINE, RN CHAE, BY GHANAYEM, BI CHAPIN, RE TI SPERMATOCYTE TOXICITY OF 2-METHOXYETHANOL (ME) IN RATS AND GUINEA-PIGS - EVIDENCE FOR THE INDUCTION OF APOPTOSIS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; ETHYLENE-GLYCOL MONOMETHYL; DNA FRAGMENTATION; THYMOCYTE APOPTOSIS; ENDONUCLEASE; ETHERS; INSITU; IDENTIFICATION; EXPOSURE AB 2-Methoxyethanol (ME) produces testicular lesions characterized by pachytene spermatocyte degeneration in rats and guinea pigs which differ in onset, severity, and morphological characteristics. In the rat, degenerating spermatocytes appear necrotic at 24 hr, while in the guinea pig they appear apoptotic 96 hr after the start of three daily doses. To further examine if the spermatocyte degeneration in both species represented necrosis or apoptosis, the extent and nature of nuclear DNA fragmentation after ME exposure were assessed both visually using an in situ nucleotide 3' end-labeling (ISEL) procedure and by DNA gel electrophoresis. Testes from rats given a single oral dose of ME (200 mg/kg) showed the expected pachytene spermatocyte degeneration 24 hr after dosing, with the nuclear chromatin degradation typical of necrosis. In contrast, testes from guinea pigs given daily oral doses of ME (200 mg/kg) showed spermatocyte degeneration at only 96 hr after the start of dosing, with marked peripheral nuclear chromatin condensation characteristic of apoptosis. Coincident with the appearance of morphologic changes, degenerating spermatocytes in both species contained fragmented DNA as revealed by the ISEL procedure. The pattern of DNA fragmentation on agarose gels in both species consisted of ordered multiples or ''ladders'' of similar to 200 base pairs, a hallmark of apoptosis, with their appearance coincident with the time course of morphologic spermatocyte degeneration and ISEL staining. Preliminary data reveal the appearance of divalent metal cation-dependent endonuclease activity at pH 7.0 in ME-treated immature (24-day-old) rat testis that produces a similar pattern of DNA fragmentation and which appears to be distinct from activity associated with the spontaneous germ cell degeneration observed in testes of this age. In summary, in vivo ME exposure induces spermatocyte apoptosis in both the rat and guinea pig despite differing morphological classifications and time of onset of cell death. Future studies will focus on further characterization of the testicular endonuclease in the rat and the potential role of increased intracellular Ca2+ as a ''triggering'' stimulus in ME-induced spermatocyte apoptosis. (C) 1995 Academic Press, Inc. RP KU, WW (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 36 TC 52 Z9 56 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1995 VL 134 IS 1 BP 100 EP 110 DI 10.1006/taap.1995.1173 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RU763 UT WOS:A1995RU76300011 PM 7676444 ER PT J AU KOHN, MC AF KOHN, MC TI ACHIEVING CREDIBILITY IN RISK ASSESSMENT MODELS SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT Workshop on Decision Support Methodologies for Human Health Risk Assessment of Toxic Substances CY OCT 18-20, 1993 CL ATLANTA, GA SP Agcy Tox Subst & Dis Registry, EPA, Halogenated Solvents Ind Alliance, NCI, NIEHS, NLM, Wright Patterson Air Force Base, Armstrong Lab DE PBPK MODELS; VALIDATION OF MODELS; RISK ASSESSMENT ID MECHANISTIC MODEL; GENE-EXPRESSION; PHARMACOKINETICS; LIVER; RAT; 1,3-BUTADIENE; RECEPTOR AB Validation of a mathematical model requires demonstrating that a model is free of mathematical errors (internal consistency), is sensitive to large but not small errors or uncertainties in parameter values (verifiability and robustness), reproduces experimental observations on the system being modeled (external consistency), and leads to testable predictions of the system's biological properties. To be heuristically valid, a model also must be a realistic representation of the actual biological system. Only then would the model's predictions be credible to the wider community of biological scientists who would use the model for risk assessment and dose or species extrapolation. Owing to incomplete data, most current dosimetric models are insufficiently realistic to pass this test of credibility. Enhancements to such models that would help achieve credibility are presented, and suggestions are offered for institutionalizing realistic modeling practices in risk assessment. RP KOHN, MC (reprint author), NATL INST ENVIRONM HLTH SCI,QUANTITAT & COMPUTAT BIOL LAB,POB 12233,MAIL DROP A3-06,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP PY 1995 VL 79 IS 1-3 BP 107 EP 114 DI 10.1016/0378-4274(95)03362-O PG 8 WC Toxicology SC Toxicology GA RW526 UT WOS:A1995RW52600016 PM 7570646 ER PT J AU BRISTOL, DW AF BRISTOL, DW TI SUMMARY AND RECOMMENDATIONS FOR SESSION-B - ACTIVITY CLASSIFICATION AND STRUCTURE-ACTIVITY RELATIONSHIP MODELING FOR HUMAN HEALTH RISK ASSESSMENT OF TOXIC-SUBSTANCES SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT Workshop on Decision Support Methodologies for Human Health Risk Assessment of Toxic Substances CY OCT 18-20, 1993 CL ATLANTA, GA SP Agcy Tox Subst & Dis Registry, EPA, Halogenated Solvents Ind Alliance, NCI, NIEHS, NLM, Wright Patterson Air Force Base, Armstrong Lab DE DECISION SUPPORT; ACTIVITY CLASSIFICATION; STRUCTURE-ACTIVITY RELATIONSHIP; HEURISTIC ANALYSIS; PATTERN RECOGNITION; FEATURE SELECTION; INTELLIGENT COMPUTER SYSTEM; MACHINE LEARNING; ARTIFICIAL INTELLIGENCE; HAZARD IDENTIFICATION; PREDICTIVE TOXICOLOGY; HUMAN EXPERT SYSTEM ID CARCINOGENICITY AB The major theme of Session B explored and assessed the current status of activity-classification (AC)(1) and structure-activity-relationship (SAR) methods developed to model adverse health effects that can result when biological systems are exposed to various chemical substances. The output from such models is intended to be used as information that supports risk assessments performed on toxic substances. Speakers gave special attention to the requirements and applications of hazard identification models. Specific aspects of the broad subject matter were augmented and explicated by audience and panel discussions during the 1.5 days available. This format stimulated the exchange of a surprisingly broad range of information and stimulating ideas. In order to gather the diverse aspects of Session B in one place, the Rapporteurs agreed that this summary would aim at providing a comprehensive overview, while Dr. Feldman's would amplify selected points of general interest. RP BRISTOL, DW (reprint author), NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP PY 1995 VL 79 IS 1-3 BP 265 EP 280 DI 10.1016/0378-4274(95)03377-W PG 16 WC Toxicology SC Toxicology GA RW526 UT WOS:A1995RW52600031 PM 7570664 ER PT J AU OLDEN, K AF OLDEN, K TI NIEHS PERSPECTIVES ON COLLABORATION AMONG GOVERNMENT, ACADEMIA, AND INDUSTRY SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT Workshop on Decision Support Methodologies for Human Health Risk Assessment of Toxic Substances CY OCT 18-20, 1993 CL ATLANTA, GA SP Agcy Tox Subst & Dis Registry, EPA, Halogenated Solvents Ind Alliance, NCI, NIEHS, NLM, Wright Patterson Air Force Base, Armstrong Lab DE ENVIRONMENTAL; TOXICOLOGY; COLLABORATION RP OLDEN, K (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP PY 1995 VL 79 IS 1-3 BP 287 EP 289 DI 10.1016/0378-4274(95)03379-Y PG 3 WC Toxicology SC Toxicology GA RW526 UT WOS:A1995RW52600033 PM 7570666 ER PT J AU VAZQUEZ, A TAPIA, JV ELIASON, WK MARTIN, BM LEBRETON, F DELEPIERRE, M POSSANI, LD BECERRIL, B AF VAZQUEZ, A TAPIA, JV ELIASON, WK MARTIN, BM LEBRETON, F DELEPIERRE, M POSSANI, LD BECERRIL, B TI CLONING AND CHARACTERIZATION OF THE CDNAS ENCODING NA+ CHANNEL-SPECIFIC TOXIN-1 AND TOXIN-2 OF THE SCORPION CENTRUROIDES-NOXIUS HOFFMANN SO TOXICON LA English DT Article ID LIMPIDUS-TECOMANUS HOFFMANN; AMINO-ACID-SEQUENCE; CROSS-RELAXATION; K+ CHANNELS; VENOM; PROTEIN; PURIFICATION; NEUROTOXINS; QUINQUESTRIATUS; MACROMOLECULES AB Using a cDNA library prepared from venomous glands of the Mexican scorpion Centruroides noxius Hoffmann the genes that encode toxins 1 and 2 were identified, cloned and sequenced. In view of the proposed mechanism for processing the mature peptides coded by these two genes, the corresponding peptide-toxins were sequenced de novo. Mass spectrometric and H-1-NMR analyses of the C-terminal peptide produced by enzymatic digestion of both toxins indicated that the last residue is serine-amide. Sequence comparison revealed that these two genes have a similarity of 56% and 80% at the amino acid and nucleotide levels, respectively. Small corrections to the published primary structures were introduced: Cn toxin 1 has an extra serine residue at position 65 and the residue in position 60 is a proline, while the amino acids at positions 34 and 35 of Cn 2 are, respectively, tyrosine and glycine. Sequence comparison of toxins from the genus Centruroides suggests the presence of at least three classes of distinct peptides in these venoms. C1 NATL AUTONOMOUS UNIV MEXICO,INST BIOTECHNOL,DEPT MOLEC RECOGNIT & STRUCT BIOL,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,CLIN NEUROSCI BRANCH,MOLEC STRUCT UNIT,BETHESDA,MD 20892. INST PASTEUR,F-75724 PARIS 15,FRANCE. RI Possani, Lourival/J-2397-2013 NR 28 TC 27 Z9 29 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD SEP PY 1995 VL 33 IS 9 BP 1161 EP 1170 DI 10.1016/0041-0101(95)00058-T PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RW056 UT WOS:A1995RW05600006 PM 8585086 ER PT J AU ROCHA, A DREYER, G POINDEXTER, RW OTTESEN, EA AF ROCHA, A DREYER, G POINDEXTER, RW OTTESEN, EA TI SYNDROME RESEMBLING TROPICAL PULMONARY EOSINOPHILIA BUT OF NON-FILARIAL ETIOLOGY - SEROLOGICAL FINDINGS WITH FILARIAL ANTIGENS SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE TROPICAL PULMONARY EOSINOPHILIA; NON-FILARIAL PULMONARY EOSINOPHILIA; SEROLOGY AB Although the tropical pulmonary eosinophilia (TPE) syndrome of filarial. aetiology has very distinctive clinical and immunological features, its clinical profile is not unique; other helminths sometimes induce similar presentations. We carefully evaluated 7 individuals with non-filarial TPE-like syndromes and found that serological tests based on detection of 'antifilarial' immunoglobulin (Ig) G, IgG4, and IgE antibodies that are usually considered diagnostic for filarial TPE were equally elevated in patients with non-filarial, TPE-like syndromes and were therefore unhelpful diagnostically. The apparent reasons were immunological hyperresponsiveness of such individuals and the shared (i.e., cross-reactive) antigenicity found in the filarial antigen preparations used routinely for diagnosis. Because appropriate treatment for those different pulmonary eosinophilia conditions requires different drugs and management, and because delay in effective treatment results in significant morbidity in such patients, diagnostic capabilities must be improved by identifying and obtaining unique antigens that can serologically discriminate between filarial TPE and other similar, but non-filarial, pulmonary eosinophilia syndromes. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP ROCHA, A (reprint author), FIOCRUZ MS,CTR PESQUISAS AGGEU MAGALHAES,CAIXA POSTAL 7472,BR-50670420 RECIFE,PE,BRAZIL. NR 9 TC 12 Z9 12 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD SEP-OCT PY 1995 VL 89 IS 5 BP 573 EP 575 DI 10.1016/0035-9203(95)90112-4 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA TH049 UT WOS:A1995TH04900036 PM 8560543 ER PT J AU SLOAND, E ALYONO, D YU, M KLEIN, H AF SLOAND, E ALYONO, D YU, M KLEIN, H TI PLATELET MEMBRANE-GLYCOPROTEINS AND MICROVESICLES IN BLOOD FROM POSTOPERATIVE SALVAGE - A STUDY IN CARDIAC BYPASS PATIENTS SO TRANSFUSION LA English DT Article ID INTRAOPERATIVE AUTO-TRANSFUSION; IB-IX COMPLEX; MONOCLONAL-ANTIBODIES; ACTIVATED PLATELETS; DOWN-REGULATION; FACTOR-VIII; IIB-IIIA; FACTOR-V; SURVIVAL; VESICLES AB Background: Transfusion of blood collected by intraoperative and postoperative salvage systems has been linked to the development of thrombocytopenia and disseminated intravascular coagulation. Although functional defects have been reported in platelets from unwashed salvaged blood, platelet membrane glycoprotein (GP) composition, a potentially important determinant of function and survival, has not been studied. Study Design and Methods: Platelets from 22 patients whose blood was salvaged at the completion of surgery were analyzed and compared to platelets obtained from the venous blood from the same patient. Platelet membranes were stained with fluorescein isothiocyanate-conjugated CD41a monoclonal antibody (anti-GPIIb/IIIa) to identify platelets, a phycoerythrin-conjugated monoclonal antibody, CD62 (anti-P-selectin) to identify activated platelets, and CD42b (anti-GPIb) or anti-GPIb/IX to assess GPIb. Samples were analyzed with a flow cytometer using software. Results: Platelets obtained from salvaged blood demonstrated lower GPIb expression (CD42b and GPIb/IX monoclonal antibody binding), higher P-selectin expression, and greater numbers of platelet-derived microvesicles. Conclusion: The clinical significance of transfusing blood containing activated platelets and microvesicles merits investigation. C1 GEORGE WASHINGTON UNIV,DEPT SURG,DIV CARDIOTHORAC SURG,WASHINGTON,DC. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP SLOAND, E (reprint author), NHLBI,BLDG 4A11,31 CTR DR,MSC 2490,BETHESDA,MD 20892, USA. NR 45 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1995 VL 35 IS 9 BP 738 EP 744 DI 10.1046/j.1537-2995.1995.35996029157.x PG 7 WC Hematology SC Hematology GA RW513 UT WOS:A1995RW51300006 PM 7570933 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - VECTORETTE, SPLINKERETTE AND BOOMERANG DNA AMPLIFICATION SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some methods of amplifying DNA other than by using the standard polymerase chain reaction (PCR). For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 7 TC 19 Z9 19 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 SEP PY 1995 VL 20 IS 9 BP 372 EP 373 DI 10.1016/S0968-0004(00)89079-9 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU814 UT WOS:A1995RU81400013 PM 7482706 ER PT J AU PTITSYN, OB AF PTITSYN, OB TI HOW THE MOLTEN GLOBULE BECAME SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note ID CARBONIC-ANHYDRASE-B; ALPHA-LACTALBUMIN; COOPERATIVE TRANSITIONS; PROTEIN MOLECULES; FOLDING REACTIONS; COMPACT STATE; MECHANISM; DENATURATION; INTERMEDIATE; EXCHANGE C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP PTITSYN, OB (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 43 TC 103 Z9 105 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD SEP PY 1995 VL 20 IS 9 BP 376 EP 379 DI 10.1016/S0968-0004(00)89081-7 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU814 UT WOS:A1995RU81400015 PM 7482708 ER PT J AU WOLFF, L PERKINS, AS AF WOLFF, L PERKINS, AS TI MOLECULAR REGULATION OF MYELOPOIESIS SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material C1 YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06520. RP WOLFF, L (reprint author), NCI,GENET LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 9 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 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD SEP PY 1995 VL 5 IS 9 BP 369 EP 371 DI 10.1016/S0962-8924(00)89072-8 PG 3 WC Cell Biology SC Cell Biology GA RQ882 UT WOS:A1995RQ88200008 PM 14732081 ER PT J AU BASSET, DE BOGUSKI, MS SPENCER, F REEVES, R GOEBL, M HIETER, P AF BASSET, DE BOGUSKI, MS SPENCER, F REEVES, R GOEBL, M HIETER, P TI COMPARATIVE GENOMICS, GENOME CROSS-REFERENCING AND XREFDB SO TRENDS IN GENETICS LA English DT Article C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. RP BASSET, DE (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,725 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 11 TC 65 Z9 65 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD SEP PY 1995 VL 11 IS 9 BP 372 EP 373 DI 10.1016/S0168-9525(00)89109-X PG 2 WC Genetics & Heredity SC Genetics & Heredity GA RT748 UT WOS:A1995RT74800010 PM 7482790 ER PT J AU PENNYPACKER, KR HONG, JS MCMILLIAN, MK AF PENNYPACKER, KR HONG, JS MCMILLIAN, MK TI IMPLICATIONS OF PROLONGED EXPRESSION OF FOS-RELATED ANTIGENS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID DNA-BINDING ACTIVITY; C-FOS; STRIATAL NEURONS; BRAIN INJURY; REACTIVE SYNAPTOGENESIS; TRANSCRIPTION FACTORS; HIPPOCAMPAL-FORMATION; RAT HIPPOCAMPUS; NERVOUS-SYSTEM; AP-1 AB The AP-1 transcription factors are composed of the Fos and Fos-related antigens as well as Jun and related proteins. These factors have been extensively studied in many diverse paradigms using acute stimuli. Recent attention has focussed on long-term elevation of Fos-related antigens in the CNS, and this is discussed by Keith Pennypacker, Jau-S. Hang and Michael McMillian. Repeated or chronic treatment elevates Fos-related antigen levels for days in many different brain regions. Both direct and indirect stimulation are responsible for the protracted increase in Fos-related antigen-immunoreactive proteins, which may modulate late onset genes involved in neuroplasticity. Understanding the role of these factors in long-lasting or permanent disease states may provide insight into potential therapeutic strategies to treat chronic CNS disorders. C1 NIEHS,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709. RP PENNYPACKER, KR (reprint author), UNIV S FLORIDA,DEPT PHARMACOL & THERAPEUT,12901 BRUCE B DOWNS BLVD MDC BOX 9,TAMPA,FL 33612, USA. RI Pennypacker, Keith/I-5092-2012 NR 55 TC 95 Z9 96 U1 0 U2 0 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 SEP PY 1995 VL 16 IS 9 BP 317 EP 321 DI 10.1016/S0165-6147(00)89061-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV333 UT WOS:A1995RV33300011 PM 7482997 ER PT J AU Ciatto, S Cecchini, S Bonardi, R Grazzini, G Mazzotta, A Zappa, M AF Ciatto, S Cecchini, S Bonardi, R Grazzini, G Mazzotta, A Zappa, M TI A feasibility study of screening for endometrial carcinoma in postmenopausal women by ultrasonography SO TUMORI LA English DT Article DE endometrial carcinoma; screening; ultrasonography ID 18 MAJOR CANCERS AB Background Abnormal endometrial thickness assessed by ultrasonography has been reported as a reliable indicator for early asymptomatic endometrial carcinoma. Study design: We evaluated the feasibility and the performance of screening by ultrasonography in a consecutive series of postmenopausal volunteers. Results: A total of 2,025 women were screened, and 117 (5.8%) showed abnormal endometrial thickness, Ninety-eight subjects consented to be assessed by outpatient endometrial biopsy, which was not possible in 32 for cervical stenosis. Three cancers were detected among 66 assessed subjects, 34 not-assessed subjects were controlled by repeat sonography (no change), and 17 were lost to follow-up. No other cancer was recorded by the local Cancer Registry among screened subjects. The prevalence/incidence ratio was 2.65:1, and the cost per screen-detected cancer was 18,571,000 Italian lire. Conclusions: Screening by endometrial sonography is feasible on a practical basis, but its efficacy needs to be proven by prospective controlled studies which would enroll large populations to ensure sufficient statistical power, considering the low incidence and the low lethality of the disease. Studies of screening for other carcinomas may be considered of higher priority. C1 NATL CANC INST,GENOA,ITALY. RP Ciatto, S (reprint author), CTR STUDIO & PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. NR 10 TC 13 Z9 13 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD SEP-OCT PY 1995 VL 81 IS 5 BP 334 EP 337 PG 4 WC Oncology SC Oncology GA TL400 UT WOS:A1995TL40000006 PM 8804449 ER PT J AU Kocsis, E Cerritelli, ME Trus, BL Cheng, NQ Steven, AC AF Kocsis, E Cerritelli, ME Trus, BL Cheng, NQ Steven, AC TI Improved methods for determination of rotational symmetries in macromolecules SO ULTRAMICROSCOPY LA English DT Article ID EQUINE HERPESVIRUS-1; PORTAL PROTEIN; PURIFICATION; IMAGES; CONNECTOR; PRODUCT AB Rotational symmetries of macromolecules are most clearly perceived in the en face projection and may be assessed by inspection of rotational power spectra calculated from electron micrographs of individual particles. However, if the symmetry is not contrasted strongly, this procedure may be inconclusive since the relevant peak may not be convincingly higher than other spectral components. To some extent, this is a sampling problem since the number of repeating elements involved is usually small. We have devised more sensitive statistical tests for rotational symmetry that pool the information contents of entire populations of particles. Both tests involve combining the rotational spectra of many particles and comparing them with the spectra of surrounding background areas. One method is based on the well known t-test which estimates whether two populations differ at a given significance level. In the second test, the ratio between the intensity of each component of the rotational spectrum and the average corresponding intensity for background areas is calculated, and thence, the cumulative product of these ratios over all particles in the data set. If a symmetry is present, this product gradually diverges; otherwise, it converges to zero. As a practical trial, the tests were applied to micrographs of negatively stained hexons of herpes simplex virus and confirmed their 6-fold symmetry. Applied to negatively stained ''connector'' proteins of bacteriophage T7 purified from a plasmid expression system, both algorithms detected polymorphism with distinct subpopulations of both 13-fold and 12-fold connectors. C1 NIAMS,NIH,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DCRT,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. NR 28 TC 67 Z9 67 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3991 J9 ULTRAMICROSCOPY JI Ultramicroscopy PD SEP PY 1995 VL 60 IS 2 BP 219 EP 228 DI 10.1016/0304-3991(95)00070-2 PG 10 WC Microscopy SC Microscopy GA TZ147 UT WOS:A1995TZ14700004 PM 7502382 ER PT J AU KORNYSHEV, AA KOSSAKOWSKI, DA LEIKIN, S AF KORNYSHEV, AA KOSSAKOWSKI, DA LEIKIN, S TI LANDAU THEORY OF A SYSTEM WITH 2 BILINEARLY COUPLED ORDER PARAMETERS IN EXTERNAL-FIELD - EXACT MEAN-FIELD SOLUTION, CRITICAL PROPERTIES AND ISOTHERMAL SUSCEPTIBILITY SO ZEITSCHRIFT FUR NATURFORSCHUNG SECTION A-A JOURNAL OF PHYSICAL SCIENCES LA English DT Article ID PHASE-TRANSITIONS; POINTS AB We present simple description of a system with two bilinearly coupled order parameters in external field based on an exact mean-field solution of the Landau Hamiltonian. It reproduces the qualitative form of the ''field-temperature'' phase diagram given by a molecular-field model acid by more sophisticated theories and experiments on metamagnets. The solution gives the same critical exponents as the molecular-field theory, but it is not restricted to the magnetic systems only and it is easier to handle, since it formulates the results in explicit analytical form. The susceptibility in this model does not diverge at the second order transition line (far from a higher order critical point separating the second and first order transition lines), but jumps down from the lower temperature wing to the higher temperature one. The jump amplitude is proportional to the square of the field in small fields and diverges in large fields dose to the higher order critical point. C1 RUSSIAN ACAD SCI, AN FRUMKIN ELECTROCHEM INST, MOSCOW 117071, RUSSIA. MOSCOW INST PHYS & TECHNOL, MOSCOW 141700, RUSSIA. NIH, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. RP KORNYSHEV, AA (reprint author), FORSCHUNGSZENTRUM JULICH, FORSCHUNGSZENTRUM, POSTFACH 1913, D-52425 JULICH, GERMANY. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 26 TC 0 Z9 0 U1 0 U2 2 PU VERLAG Z NATURFORSCH PI TUBINGEN PA POSTFACH 2645, 72016 TUBINGEN, GERMANY SN 0932-0784 J9 Z NATURFORSCH A JI Z. Naturfors. Sect. A-J. Phys. Sci. PD SEP PY 1995 VL 50 IS 9 BP 789 EP 794 PG 6 WC Chemistry, Physical; Physics, Multidisciplinary SC Chemistry; Physics GA TA037 UT WOS:A1995TA03700001 ER PT J AU WALLQVIST, A COVELL, DG AF WALLQVIST, A COVELL, DG TI FREE-ENERGY COST OF BENDING N-DODECANE IN AQUEOUS-SOLUTION - INFLUENCE OF THE HYDROPHOBIC EFFECT AND SOLVENT-EXPOSED AREA SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID PROTEIN-FOLDING THERMODYNAMICS; EFFECTIVE PAIR POTENTIALS; MONTE-CARLO SIMULATION; MOLECULAR-DYNAMICS; NORMAL-BUTANE; COMPUTER-SIMULATION; NUCLEIC-ACIDS; WATER; HYDRATION; EQUILIBRIUM AB Computer simulations of the free energy associated with different conformations of a single n-dodecane molecule in liquid water are reported. The alkane chain was monitored as a function of the end-to-end distance, essentially following the formation of a hairpin bend from an initially fully extended state. While elongated conformations are among the most stable state in both gas and solvated states, the influence of the solvent is to favor more compact states. At the most compact conformation, the hairpin bend, the solvent imparts a stabilizing free-energy contribution of 6 kJ/mol. The torsional strain of bending the molecule into this hairpin conformation is partly relieved by the reduction of entropically unfavorable water molecules associated with the reduction in the alkane's surface exposed area. The resultant solvent contribution to the free-energy change is characterized by an unfavorable enthalpic and a competing favorable entropic (-T Delta S) contribution. The conformational change associated with the transition from an extended state to a compact state for n-dodecane is accompanied by a relatively small, non-uniform change in surface exposed area. A simplified model of the free energy as a function of this area can account for the gross effects but is unable pick up the molecular details inherent in the system. RP WALLQVIST, A (reprint author), SCI APPLICAT INT CORP, NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 48 TC 27 Z9 28 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD AUG 31 PY 1995 VL 99 IS 35 BP 13118 EP 13125 DI 10.1021/j100035a013 PG 8 WC Chemistry, Physical SC Chemistry GA RR846 UT WOS:A1995RR84600013 ER PT J AU SUTTER, RW HADLER, SC MCQUILLAN, G GERGEN, PJ AF SUTTER, RW HADLER, SC MCQUILLAN, G GERGEN, PJ TI PROTECTION AGAINST TETANUS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID VACCINATION C1 NATL CTR HLTH STAT,ROCKVILLE,MD 20782. NIH,BETHESDA,MD 20892. RP SUTTER, RW (reprint author), CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 31 PY 1995 VL 333 IS 9 BP 600 EP 600 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RQ751 UT WOS:A1995RQ75100024 ER PT J AU PARK, JM CHOI, IS KANG, SG LEE, JY HATFIELD, DL LEE, BJ AF PARK, JM CHOI, IS KANG, SG LEE, JY HATFIELD, DL LEE, BJ TI UPSTREAM PROMOTER ELEMENTS ARE SUFFICIENT FOR SELENOCYSTEINE TRNA([SER]SEC) GENE-TRANSCRIPTION AND TO DETERMINE THE TRANSCRIPTION START POINT SO GENE LA English DT Article DE TATA BOX; PROXIMAL SEQUENCE ELEMENT; TSP; INTERNAL BOX A; INTERNAL BOX B; PRIMER EXTENSION ID PHOSPHOSERINE TRANSFER-RNA; TRANSFER RNA(SER)SEC GENE; POLYMERASE-III AB The TATA box, located upstream at about nt -30, and the proximal sequence element, located at about nt -60, are both essential and sufficient for basal level transcription of the Xenopus laevis (Xl) selenocysteine (Sec) tRNA([Ser]Sec) gene as demonstrated by its microinjection into Xl oocytes. Point mutations within either of these regions abolish transcription, while deletion of the internal boxA dement or insertion of 13 nt within the internal boxB element does not impair transcription, The latter mutations (within the internal regions) affect processing of the 3'-trailer sequence. Replacement of the tRNA([Ser]Sec) coding sequence with an Escherichia coli M1 RNA gene resulted in expression of the E. coli gene governed by the upstream tRNA([Ser]Sec) promoter elements. These studies demonstrate unequivocally that the upstream promoter elements are sufficient for the basal level of tRNA([Ser]Sec) gene transcription. Primer extension studies with spacer mutants show that the internal elements do not play a role in selecting the transcription start point (tsp), but that selection of the tsp is determined by the region upstream from the gene. Further, studies with spacer mutants show that the distance between the TATA box and the tsp is quite likely the critical factor in selecting the position of tsp. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. SEOUL NATL UNIV,INST MOLEC BIOL & GENET,GENET MOLEC LAB,SEOUL 151742,SOUTH KOREA. NR 17 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 30 PY 1995 VL 162 IS 1 BP 13 EP 19 DI 10.1016/0378-1119(95)00340-C PG 7 WC Genetics & Heredity SC Genetics & Heredity GA RV288 UT WOS:A1995RV28800003 PM 7557401 ER PT J AU REKHARSKY, MV GOLDBERG, RN SCHWARZ, FP TEWARI, YB ROSS, PD YAMASHOJI, Y INOUE, Y AF REKHARSKY, MV GOLDBERG, RN SCHWARZ, FP TEWARI, YB ROSS, PD YAMASHOJI, Y INOUE, Y TI THERMODYNAMIC AND NUCLEAR-MAGNETIC-RESONANCE STUDY OF THE INTERACTIONS OF ALPHA-CYCLODEXTRIN AND BETA-CYCLODEXTRIN WITH MODEL SUBSTANCES - PHENETHYLAMINE, EPHEDRINES, AND RELATED SUBSTANCES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID AQUEOUS-SOLUTION; INCLUSION-COMPOUNDS; MOLECULAR RECOGNITION; COMPLEX-FORMATION; CYCLOMALTOHEXAOSE; BINDING; TITRATION; WATER; 25-DEGREES; STABILITY AB Titration calorimetry was used to measure equilibrium constants and standard molar enthalpies for the reactions of phenethylamine, ephedrines, and related substances with alpha- and beta-cyclodextrin. Changes in the chemical shifts Delta delta of both the ligand and cyclodextrin protons were measured with NMR. The thermodynamic results have been examined in terms of structural features of the ligand that affect these interactions such as the separation of the charge at an amino group and the aromatic ring, steric effects, the presence of additional functional groups (amino, hydroxy, methoxy, and methyl) attached to the aromatic ring, the presence and location of hydroxy group(s) on the ligand, changes in the chirality of the ligand, and the flexibility of the organic molecules attached to the aromatic ring. It was found that the values of thermodynamic quantities for these reactions in phosphate and acetate buffers were different. This difference is attributable to the presence of a hydrophobic alkyl group in the neutral acetic acid molecule and its interaction with the cyclodextrins. Also, there are significant differences in the thermodynamic quantities for the reactions of the chiral isomers of ephedrine and pseudoephedrine in their reactions with beta-cyclodextrin. A plot of the standard molar enthalpy vs the standard molar entropy for the reactions of these chiral isomers with alpha- and beta-cyclodextrin is linear; the relative order of the ephedrines and pseudoephedrines in the enthalpy-entropy plot is the same for the reactions of these substances with both alpha- and beta-cyclodextrin. NMR studies demonstrated that the magnitude of the upfield shifts of the cyclodextrin's H3 and H5 protons, Delta delta(H3) and Delta delta(H5), and their relative ratio, Delta delta(H5)/Delta delta(H3), can be used, respectively, as a measure of the complex stability and the depth of inclusion of the ligand into the cavity. The equilibrium constants determined by titration calorimetry correlate well with the changes in chemical shifts Delta delta determined by NMR. C1 NATL INST STAND & TECHNOL,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. OSAKA UNIV,FAC ENGN,DEPT MOLEC CHEM,SUITA,OSAKA 565,JAPAN. NR 39 TC 181 Z9 181 U1 6 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 30 PY 1995 VL 117 IS 34 BP 8830 EP 8840 DI 10.1021/ja00139a017 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA RR735 UT WOS:A1995RR73500017 ER PT J AU CHIBA, H KOMATSU, K LEE, YC TOMIZUKA, T STROTT, CA AF CHIBA, H KOMATSU, K LEE, YC TOMIZUKA, T STROTT, CA TI THE 3'-TERMINAL EXON OF THE FAMILY OF STEROID AND PHENOL SULFOTRANSFERASE GENES IS SPLICED AT THE N-TERMINAL GLYCINE OF THE UNIVERSALLY CONSERVED GXXGXXK MOTIF THAT FORMS THE SULFONATE DONOR BINDING-SITE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ESTROGENS; NEUTRAL STEROIDS; PHENOLS ID LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; MOLECULAR-CLONING; ESTROGEN SULFOTRANSFERASE; RAT-LIVER; ARYL SULFOTRANSFERASE; SEQUENCE-ANALYSIS; MOUSE-LIVER; CDNA; EXPRESSION; PROTEINS AB The guinea pig estrogen sulfotransferase gene has been cloned and compared to three other cloned steroid and phenol sulfotransferase genes (human estrogen sulfotransferase, human phenol sulfotransferase, and guinea pig 3 alpha-hydroxysteroid sulfotransferase). The four sulfotransferase genes demonstrate a common outstanding feature: the splice sites for their 3'-terminal exons are identically located. That is, the 3'-terminal exon splice sites involve a glycine that constitutes the N-terminal glycine of an invariably conserved GXXGXXK motif present in all steroid and phenol sulfotransferases for which primary structures are known, This consistency strongly suggests that all steroid and phenol sulfotransferase genes will be similarly spliced. The GXXGXXK motif forms the active binding site for the universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate, Amino acid sequence alignment of 19 cloned steroid and phenol sulfotransferases starting with the GXXGXXK motif indicates that the 3'-terminal exon for each steroid and phenol sulfotransferase gene encodes a similarly sized C-terminal fragment of the protein, Interestingly, on further analysis of the alignment, three distinct amino acid sequence patterns emerge, The presence of the conserved functional GXXGXXK motif suggests that the protein domains encoded by steroid and phenol sulfotransferase 3'-terminal exons have evolved from a common ancestor, Furthermore, it is hypothesized that during the course of evolution, the 3'-terminal exon further diverged into at least three sulfotransferase subdivisions: a phenol or aryl group, an estrogen or phenolic steroid group, and a neutral steroid group. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,STEROID REGULAT SECT,BETHESDA,MD 20892. NR 31 TC 17 Z9 17 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 29 PY 1995 VL 92 IS 18 BP 8176 EP 8179 DI 10.1073/pnas.92.18.8176 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400019 PM 7667264 ER PT J AU HISATAKE, K OHTA, T TAKADA, R GUERMAH, M HORIKOSHI, M NAKATANI, Y ROEDER, RG AF HISATAKE, K OHTA, T TAKADA, R GUERMAH, M HORIKOSHI, M NAKATANI, Y ROEDER, RG TI EVOLUTIONARY CONSERVATION OF HUMAN TATA-BINDING-POLYPEPTIDE-ASSOCIATED FACTORS TAF(II)31 AND TAF(II)80 AND INTERACTIONS OF TAF(II)80 WITH OTHER TAFS AND WITH GENERAL TRANSCRIPTION FACTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMEDIATE EARLY PROTEIN; RNA POLYMERASE-II; PREINITIATION COMPLEX; PROMOTER INTERACTIONS; ACTIVATION DOMAIN; TFIID COMPONENTS; COACTIVATORS; SUBUNIT; IDENTIFICATION; UPSTREAM AB Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription. To investigate protein-protein interactions involved in TFIID assembly and in TAF-mediated activator functions, we have cloned and expressed cDNAs encoding human TAF(II)80 and TAF(II)31. Coimmunoprecipitation assays showed that TAF(II)80 interacted with TAF(II)250, TAF(II)31, TAF(II)20, and TBP, but not with TAF(II)55. Similar assays showed that TAF(II)80 interacted with TFIIE alpha and with TFIIF alpha (RAP74) but not with TFIIB, TFIIE beta, or TFIIF beta (RAP30). Further studies with TAF(II)80 mutations revealed three distinct interaction domains which fall within regions conserved in human TAF(II)80, Drosophila TAF(II)60, and yeast TAF(II)60. The N terminus of TAF(II)80 (residues 1-100) interacts with both TAF(II)31 and TAF(II)20, while two C-terminal regions are involved, respectively, in interactions with TAF(II)250 and TPIIF alpha (RAP74) (residues 203-276) and with TBIP and TFIIE alpha (residues 377-505). The interactions between TAF(II)80 and general factors TFIIE alpha and TFIIF alpha (RAP74) could be important for recruitment of GTFs during activator-dependent transcription, Because TAPs 80, 31, and 20 show sequence similarities to histones H4, H3, and H2B, as well as some parallel interactions, this subset of TAFs may form a related core structure within TFIID. C1 ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. NICHHD,BETHESDA,MD 20892. FU NCI NIH HHS [CA42567]; NIAID NIH HHS [AI27397]; NIGMS NIH HHS [GM45250] NR 35 TC 60 Z9 64 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 AUG 29 PY 1995 VL 92 IS 18 BP 8195 EP 8199 DI 10.1073/pnas.92.18.8195 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400023 PM 7667268 ER PT J AU GAO, WY JOHNS, DG CHOKEKIJCHAI, S MITSUYA, H AF GAO, WY JOHNS, DG CHOKEKIJCHAI, S MITSUYA, H TI DISPARATE ACTIONS OF HYDROXYUREA IN POTENTIATION OF PURINE AND PYRIMIDINE 2',3'-DIDEOXYNUCLEOSIDE ACTIVITIES AGAINST REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENZYMATIC ASSAY; CELL-CYCLE; PHOSPHORYLATION; KINASE; DNA; 2',3'-DIDEOXYCYTIDINE; 3'-AZIDOTHYMIDINE; LYMPHOCYTES; REDUCTASE AB We and other groups have recently reported the potentiation by ribonucleotide reductase inhibitors such as hydroxyurea of the anti-human immunodeficiency virus type 1 (HIV-1) activity of purine and pyrimidine 2',3'-dideoxynucleosides in both resting and phytohemagglutinin-stimulated peripheral blood mononuclear cells. Little agreement prevails, however, as to the mechanism of the synergistic effects described. We report here that in phytophemagglutinin-stimulated peripheral blood mononuclear cells, two mechanisms exist for the potentiation of the anti-HIV-1 activity by low-dose hydroxyurea of the purine-based dideoxynucleoside 2',3'-dideoxyinosine and the pyrimidine-based dideoxynucleosides 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine. For 2',3'-dideoxyinosine, the enhancement arises from a specific depletion of dATP by hydroxyurea, resulting in a favorable shift of the 2',3'-dideoxyadenosine 5'-triphosphate/dATP ratio. For the pyrimidine dideoxynucleosides 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine, the more modest anti-HIV enhancement results from hydroxyurea-induced increases of pyrimidine kinase activities in the salvage pathway and, hence, increased 5'-phosphorylation of these drugs, while depletion of the corresponding deoxynucleoside 5'-triphosphates (dTTP and dCTP) plays no significant role. C1 NCI,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RP GAO, WY (reprint author), NCI,MED BRANCH,EXPTL RETROVIROL SECT,BLDG 10,ROOM 5A24,BETHESDA,MD 20892, USA. NR 26 TC 64 Z9 64 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 AUG 29 PY 1995 VL 92 IS 18 BP 8333 EP 8337 DI 10.1073/pnas.92.18.8333 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400051 PM 7667290 ER PT J AU CORNETTE, JL MARGALIT, H BERZOFSKY, JA DELISI, C AF CORNETTE, JL MARGALIT, H BERZOFSKY, JA DELISI, C TI PERIODIC VARIATION IN SIDE-CHAIN POLARITIES OF T-CELL ANTIGENIC PEPTIDES CORRELATES WITH THEIR STRUCTURE AND ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AMPHIPATHICITY; HYDROPHOBIC MOMENT ID TOXIC LYMPHOCYTES-T; CLASS-I H-2K(B); AMPHIPATHIC STRUCTURES; PROTEIN ANTIGENS; ENVELOPE PROTEIN; VIRAL PEPTIDES; MHC; COMPLEX; BINDING; MOLECULE AB We present an analysis that synthesizes information on the sequence, structure, and motifs of antigenic peptides, which previously appeared to be in conflict, Fourier analysis of T-cell antigenic peptides indicates a periodic variation in amino acid polarities of 3-3.6 residues per period, suggesting an amphipathic alpha-helical structure, However, the diffraction patterns of major histocompatibility complex (MHC) molecules indicate that their ligands are in an extended non-alpha-helical conformation, We present two mutually consistent structural explanations for the source of the alpha-helical periodicity, based on an observation that the side chains of MHC-bound peptides generally partition with hydrophobic (hydrophilic) side chains pointing into (out of) the cleft, First, an analysis of haplotype-dependent peptide motifs indicates that the locations of their defining residues tend to force a period 3-4 variation in hydrophobicity along the peptide sequence, in a manner consistent with the spacing of pockets in the MHC. Second, recent crystallographic determination of the structure of a peptide bound to a class II MHC molecule reveals an extended but regularly twisted peptide with a rotation angle of about 130 degrees, We show that similar structures with rotation angles of 100-130 degrees are energetically acceptable and also span the Length of the MHC cleft. These results provide a sound physical chemical and structural basis for the existence of a haplotype-independent antigenic motif which can be particularly important in limiting the search time for antigenic peptides. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MOLEC GENET,IL-91010 JERUSALEM,ISRAEL. NCI,METAB BRANCH,BETHESDA,MD 20892. BOSTON UNIV,DEPT BIOMED ENGN,BOSTON,MA 02215. RP CORNETTE, JL (reprint author), IOWA STATE UNIV SCI & TECHNOL,DEPT MATH,AMES,IA 50011, USA. RI Margalit, Hanah/H-1651-2013 FU NIAID NIH HHS [AI30535] 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 AUG 29 PY 1995 VL 92 IS 18 BP 8368 EP 8372 DI 10.1073/pnas.92.18.8368 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RR844 UT WOS:A1995RR84400058 PM 7667297 ER PT J AU PAZZAGLIA, PJ POST, RM RUBINOW, D KLING, MA HUGGINS, TS SUNDERLAND, T AF PAZZAGLIA, PJ POST, RM RUBINOW, D KLING, MA HUGGINS, TS SUNDERLAND, T TI CEREBROSPINAL-FLUID TOTAL PROTEIN IN PATIENTS WITH AFFECTIVE-DISORDERS SO PSYCHIATRY RESEARCH LA English DT Article DE BIPOLAR DISORDER; GENDER EFFECTS; UNIPOLAR DEPRESSION ID BLOOD-BRAIN-BARRIER; EPILEPTIC SEIZURES AB Cerebrospinal fluid (CSF) total protein was evaluated in 240 patients with affective disorders and compared with findings in 55 normal comparison subjects, Subtype diagnoses were as follows: bipolar I(n = 108, 47 men, 61 women); bipolar type II (n = 67, 26 men, 41 women); and unipolar (n = 65, 22 men, 43 women). Men had significantly elevated values compared with women. In men with bipolar I disorder, mean CSF protein levels were found to be significantly elevated over those in normal subjects, with 31.9% above the traditional normal range cutoff of 45 mg/dl. Moreover, CSF protein levels in male bipolar I patients were found to be positively correlated with severity of depression at the time of the lumbar puncture and with duration of illness, It thus appears that increased protein levels may be associated with illness severity or progression in male patients with bipolar I disorder. Although elevated CSF protein is a nonspecific marker of cerebral pathology, further search for the potential underlying pathophysiological 'mechanisms related to this finding would now appear to be warranted. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 28 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 28 PY 1995 VL 57 IS 3 BP 259 EP 266 DI 10.1016/0165-1781(95)02704-Z PG 8 WC Psychiatry SC Psychiatry GA RT646 UT WOS:A1995RT64600008 PM 7501736 ER PT J AU QUINTERO, RA JOHNSON, MP ROMERO, R SMITH, C ARIAS, F GUEVARAZULOAGA, F COTTON, DB EVANS, MI AF QUINTERO, RA JOHNSON, MP ROMERO, R SMITH, C ARIAS, F GUEVARAZULOAGA, F COTTON, DB EVANS, MI TI IN-UTERO PERCUTANEOUS CYSTOSCOPY IN THE MANAGEMENT OF FETAL LOWER OBSTRUCTIVE UROPATHY SO LANCET LA English DT Article ID URINARY-TRACT OBSTRUCTION; CONGENITAL HYDRONEPHROSIS; RENAL-FUNCTION; INTERVENTION; INUTERO; BIOCHEMISTRY; DIAGNOSIS AB In fetuses with lower obstructive uropathy, sonography cannot establish the cause of obstruction. We assessed whether percutaneous fetal cystoscopy could be useful in the evaluation and treatment of obstructive defects in utero. We inserted a fibreoptic endoscope through the lumen of the needle or trocar into the fetal bladder at the time of vesicocentesis or vesicoamniotic-shunt placement and looked at the the urethra, bladder neck, and ureteral orifices. Urethral vesicoamniotic shunting was considered in suitable cases; otherwise a percutaneous shunt was inserted. Fetal cystoscopy was possible in 11 of 13 patients referred. The bladder mucosa appeared haemorrhagic or oedematous in three, The ureteral orifices were seen in 9/11 fetuses, dilation was seen in five, but was only suspected in two by ultrasound. Ureteral webs were noted in two other fetuses. Two of seven fetuses underwent urethral vesicoamniotic shunting; urethral patency was achieved with urethral probing alone in one fetus. The remaining four fetuses were shunted with a standard technique. Fetal cystoscopy helps define the underlying conditions responsible for sonographic findings of lower obstructive uropathy, and allows the introduction of new treatments. C1 WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI. WAYNE STATE UNIV,HUTZEL HOSP,DEPT PEDIAT UROL,DETROIT,MI. ST JOHNS MERCY HOSP,DEPT OBSTET & GYNECOL,ST LOUIS,MO. CENT UNIV VENEZUELA,HOSP UNIV CARACAS,UNIDAD PERINATOL,CARACAS,VENEZUELA. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD. NR 25 TC 94 Z9 96 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD AUG 26 PY 1995 VL 346 IS 8974 BP 537 EP 540 DI 10.1016/S0140-6736(95)91381-5 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA RQ986 UT WOS:A1995RQ98600009 PM 7658779 ER PT J AU WEINBERGER, DR AF WEINBERGER, DR TI FROM NEUROPATHOLOGY TO NEURODEVELOPMENT SO LANCET LA English DT Article ID CHRONIC-SCHIZOPHRENIA; ABNORMALITIES; BRAIN; DISTURBANCES; LOBE RP WEINBERGER, DR (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 40 TC 448 Z9 456 U1 2 U2 10 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD AUG 26 PY 1995 VL 346 IS 8974 BP 552 EP 557 DI 10.1016/S0140-6736(95)91386-6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RQ986 UT WOS:A1995RQ98600014 PM 7544856 ER PT J AU RHYU, MS KNOBLICH, JA AF RHYU, MS KNOBLICH, JA TI SPINDLE ORIENTATION AND ASYMMETRIC CELL FATE SO CELL LA English DT Review ID SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; DROSOPHILA; PROSPERO; DIVISION C1 UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. RP RHYU, MS (reprint author), NCI,BETHESDA,MD 20892, USA. RI Knoblich, Juergen/C-2974-2015 OI Knoblich, Juergen/0000-0002-6751-3404 NR 21 TC 66 Z9 66 U1 3 U2 4 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 25 PY 1995 VL 82 IS 4 BP 523 EP 526 DI 10.1016/0092-8674(95)90022-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RR734 UT WOS:A1995RR73400001 PM 7664329 ER PT J AU AULAKH, CS MAZZOLAPOMIETTO, P MURPHY, DL AF AULAKH, CS MAZZOLAPOMIETTO, P MURPHY, DL TI LONG-TERM ANTIDEPRESSANT TREATMENTS ALTER 5-HT2A AND 5-HT2C RECEPTOR-MEDIATED HYPERTHERMIA IN FAWN-HOODED RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DOI (1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE); M-CPP (M-CHLOROPHENYLPIPERAZINE); DEPRESSION, GENETIC MODEL; CLORGYLINE; IMIPRAMINE; CLOMIPRAMINE ID NEURO-ENDOCRINE RESPONSES; ANTI-DEPRESSANT TREATMENT; SPRAGUE-DAWLEY RATS; SEROTONIN UPTAKE; HORMONE-RELEASE; M-CPP; BINDING; CHLOROPHENYLPIPERAZINE; LITHIUM; BRAIN AB We have recently demonstrated that hyperthermia induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and m-chlorophenylpiperazine (m-CPP) are separately mediated by selective stimulation of 5-HT2A and 5-HT2C receptors, respectively in Wistar rats. Furthermore, hyperthermia induced by either DOI or m-CPP was found to be significantly less in Fawn-Hooded rats (a rat strain suggested to represent a genetic model of depression) relative to Wistar rats. In the present study, we studied the effects of long-term antidepressant treatments on DOI (2.5 mg/kg)-induced and m-CPP (2.5 mg/kg)-induced hyperthermia in male Fawn-Hooded rats. Long-term (21 days) treatment with the tricyclic antidepressants, imipramine or clomipramine (each 5 mg/kg/day), attenuated DOI-induced hyperthermia, while m-CPP-induced hyperthermia was accentuated. On the other hand, long-term (21 days) treatment with the monoamine oxidase type-A inhibiting antidepressant, clorgyline (1 mg/kg/day), did not modify m-CPP-induced hyperthermia, but significantly attenuated DOI-induced hyperthermia. These findings demonstrate that long-term antidepressant treatments alter 5-HT2A and 5-HT2C receptor-mediated hyperthermia in a genetic animal model of depression. RP AULAKH, CS (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D41,10 CTR DR MSC 1264,BETHESDA,MD 20892, USA. NR 36 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 25 PY 1995 VL 282 IS 1-3 BP 65 EP 70 DI 10.1016/0014-2999(95)00279-T PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RT477 UT WOS:A1995RT47700007 PM 7498290 ER PT J AU BAUMANN, MH BECKETTS, KM ROTHMAN, RB AF BAUMANN, MH BECKETTS, KM ROTHMAN, RB TI EVIDENCE FOR ALTERATIONS IN PRESYNAPTIC SEROTONERGIC FUNCTION DURING WITHDRAWAL FROM CHRONIC COCAINE IN RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 5-HT (5-HYDROXYTRYPTAMINE, SEROTONIN); COCAINE; FENFLURAMINE; CORTICOSTERONE, PRESYNAPTIC ID NEUROENDOCRINE RESPONSES; PARA-CHLOROAMPHETAMINE; DEPRESSED-PATIENTS; L-TRYPTOPHAN; AGONIST DOI; BRAIN; FENFLURAMINE; DOPAMINE; STIMULATION; FLUOXETINE AB The effects of repeated cocaine administration on serotonin (5-hydroxytryptamine, 5-HT) function were investigated by comparing the corticosterone response to 5-HT receptor agonists in cocaine-treated and vehicle-treated rats. Male rats were fitted with indwelling jugular catheters and received cocaine (15 mg/kg i.p., b.i.d.) or saline for 7 days. Rats were challenged with either saline, the 5-HT releaser fenfluramine (1.2 mg/kg i.v.), the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 50 mu g/kg i.v.), or the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 100 mu g/kg i,v,) 42 h and 8 days after the final chronic treatment. Repeated blood samples were withdrawn immediately before and at 15, 30 and 60 min after acute challenge injections. All 5-HT receptor agonists increased plasma corticosterone, but the fenfluramine-induced rise in corticosterone was significantly attenuated in cocaine-treated rats withdrawn for 42 h. This blunted response to fenfluramine exhibited only partial recovery when examined at 8 days postchronic treatment. Corticosterone responses to 8-OH-DPAT and DOI were not affected by cocaine exposure. Our data suggest that chronic cocaine produces deficits in presynaptic 5-HT function, and alterations in 5-HT neurotransmission may underlie the dysphoria experienced by abstinent cocaine users. Neuroendocrine challenge tests should be performed in human addicts to evaluate potential 5-HT dysfunction associated with cocaine abuse. RP BAUMANN, MH (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,CLIN PSYCHOPHARMACOL SECT,4940 EASTERN AVE,BLDG C,BALTIMORE,MD 21224, USA. NR 51 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 25 PY 1995 VL 282 IS 1-3 BP 87 EP 93 DI 10.1016/0014-2999(95)00280-X PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RT477 UT WOS:A1995RT47700010 PM 7498293 ER PT J AU KWONG, CH ADAMS, AG LETO, TL AF KWONG, CH ADAMS, AG LETO, TL TI CHARACTERIZATION OF THE EFFECTOR-SPECIFYING DOMAIN OF RAC INVOLVED IN NADPH OXIDASE ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEIN; CHRONIC GRANULOMATOUS-DISEASE; RESPIRATORY BURST OXIDASE; SIGNAL TRANSDUCTION; EXCHANGE PROTEINS; IN-VITRO; SUPEROXIDE; COMPONENTS; MEMBRANE; CLONING AB Production of microbicidal oxidants by phagocytic leukocytes requires activation of a latent NADPH oxidase by the coordinated assembly of a membrane-associated flavocytochrome b(558), with three cytosolic components, p47(phox), p67(phox), and the low molecular weight GTP-binding protein Rac. Rac1 and Rac2 have 92% sequence identity and are both active in supporting the oxidase, while CDC42Hs, the closest relative to Pac with 70% sequence identity, only weakly supports oxidase activation in vitro, We have used CDC42Hs as a foil to identify residues in Pac that are critical for oxidase activation. Most of the divergent sequences of CDC42Hs could be incorporated into Rac-CDC42Hs chimeric proteins without affecting cell-free NADPH oxidase activity, However, incorporation of the amino-terminal segment of CDC42Hs (residues 1-40), which differs from Rad by only four residues (positions 3, 27, 30, and 33), resulted in a marked loss of oxidase activation capacity. Point mutagenesis studies showed that this was due to changes at residues 27 and 30, but nob residues 3 and 33. Conversely, incorporation of the amino terminus of Rac1 (residues 1-40) into CDC42Hs increased its activity to that of Rac1, indicating that this terminus contains the effector-specifying domain of Rac. Taken together, these studies show that the difference in the activity between CDC42Hs and Rac1 is due entirely to differences in amino acids at position 27 and 30. RP KWONG, CH (reprint author), NIAID,HOST DEF LAB,BETHESDA,MD 20892, USA. NR 42 TC 54 Z9 54 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 AUG 25 PY 1995 VL 270 IS 34 BP 19868 EP 19872 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RQ991 UT WOS:A1995RQ99100031 PM 7649999 ER PT J AU GOTTESMAN, MM LEVINE, AS AF GOTTESMAN, MM LEVINE, AS TI THE DEVI CASE AND MORE SO SCIENCE LA English DT Letter C1 NICHHD,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 25 PY 1995 VL 269 IS 5227 BP 1029 EP 1030 DI 10.1126/science.7652536 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RQ748 UT WOS:A1995RQ74800002 PM 7652536 ER PT J AU ROBBINS, JB SCHNEERSON, R BENNETT, JE AF ROBBINS, JB SCHNEERSON, R BENNETT, JE TI THE DEVI CASE AND MORE SO SCIENCE LA English DT Letter RP ROBBINS, JB (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 25 PY 1995 VL 269 IS 5227 BP 1033 EP 1033 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RQ748 UT WOS:A1995RQ74800011 ER PT J AU MARONPOT, RR FOX, T MALARKEY, DE GOLDSWORTHY, TL AF MARONPOT, RR FOX, T MALARKEY, DE GOLDSWORTHY, TL TI MUTATIONS IN THE RAS PROTOONCOGENE - CLUES TO ETIOLOGY AND MOLECULAR PATHOGENESIS OF MOUSE-LIVER TUMORS SO TOXICOLOGY LA English DT Review DE RAS PROTOONCOGENE; LIVER TUMORS; RAS ACTIVATION; MOUSE CARCINOGENICITY ID PRIMARY HEPATOCELLULAR-CARCINOMA; POLYMERASE CHAIN-REACTION; HA-RAS; B6C3F1 MOUSE; N-NITROSODIETHYLAMINE; LUNG-TUMORS; K-RAS; PROTOONCOGENE ACTIVATION; CHEMICAL CARCINOGENESIS; POINT MUTATIONS C1 NIEHS,RES TRIANGLE PK,NC 27709. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NR 106 TC 120 Z9 121 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD AUG 25 PY 1995 VL 101 IS 3 BP 125 EP 156 DI 10.1016/0300-483X(95)03112-S PG 32 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RU583 UT WOS:A1995RU58300001 PM 7676462 ER PT J AU KELLY, JF MASON, RP DENISOVA, NA JOSEPH, JA ERAT, S ROTH, GS AF KELLY, JF MASON, RP DENISOVA, NA JOSEPH, JA ERAT, S ROTH, GS TI AGE-RELATED IMPAIRMENT IN STRIATAL MUSCARINIC CHOLINERGIC SIGNAL-TRANSDUCTION IS ASSOCIATED WITH REDUCED MEMBRANE BILAYER WIDTH MEASURED BY SMALL-ANGLE X-RAY-DIFFRACTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CHOLESTEROL; BRAIN; PHOSPHOLIPIDS; MYELIN AB In order to determine whether age-related changes in neuronal membrane structure contribute to previously reported changes in muscarinic cholinergic signal transduction, striata from 3, 13 and 23 month old F344 male rats were examined for both carbachol-stimulated low Km GTPase activity and membrane one-dimensional electron density profile using small angle X-ray diffraction. Increasing age was associated with both a reduction in stimulated GTPase activity and a decrease in membrane bilayer width. These findings suggest the possibility that fundamental membrane structural changes may contribute to alterations in signal transduction seen with aging. C1 MED COLL PENN,PITTSBURGH,PA 15212. HAHNEMANN UNIV,PITTSBURGH,PA 15212. TUFTS UNIV,USDA ARS,CTR HUMAN NUTR,BOSTON,MA 02111. RP KELLY, JF (reprint author), NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224, USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 24 PY 1995 VL 213 IS 3 BP 869 EP 874 DI 10.1006/bbrc.1995.2209 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RQ727 UT WOS:A1995RQ72700018 PM 7654249 ER PT J AU YUWEN, H KAZACHKOV, Y MORIMITSU, Y TABOR, E AF YUWEN, H KAZACHKOV, Y MORIMITSU, Y TABOR, E TI IDENTIFICATION OF 2 P53 BINDING-PROTEINS USING A RECOMBINANT VACCINIA VIRUS CONTAINING THE WILD-TYPE HUMAN P53 GENE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELLS; SUPPRESSOR; ONCOGENE; ANTIGEN AB A recombinant vaccinia virus was constructed using the wild-type human p53 gene as an insert. The p53 protein produced by this recombinant virus was used to investigate p53 binding proteins in seventeen cell lines, including derived from human hepatocellular carcinoma, four from other human cancers, and three from non-human primate tissues. In all 17 cell lines tested, two proteins of 40 kD and 50 kD were identified that bound to wild-type p53 and that may be cellular regulators of p53 function. (C) 1995 Academic Press, Inc. C1 NCI,BETHESDA,MD 20892. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 24 PY 1995 VL 213 IS 3 BP 986 EP 993 DI 10.1006/bbrc.1995.2226 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RQ727 UT WOS:A1995RQ72700035 PM 7654264 ER PT J AU SHIBA, K RIPMASTER, T SUZUKI, N NICHOLS, R PLOTZ, P NODA, T SCHIMMEL, P AF SHIBA, K RIPMASTER, T SUZUKI, N NICHOLS, R PLOTZ, P NODA, T SCHIMMEL, P TI HUMAN ALANYL-TRANSFER-RNA SYNTHETASE - CONSERVATION IN EVOLUTION OF CATALYTIC CORE AND MICROHELIX RECOGNITION SO BIOCHEMISTRY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; ESCHERICHIA-COLI; BOMBYX-MORI; ENZYMATIC AMINOACYLATION; CHEMICAL SYNTHESIS; MAJOR DETERMINANT; GLYCYL-TRANSFER; MINOR GROOVE; SEQUENCE; IDENTITY AB The class II Escherichia coli and human alanyl-tRNA synthetases cross-acylate their respective tRNAs and require, for aminoacylation, an acceptor helix G3:U70 base pair that is conserved in evolution. We report here the primary structure and expression in the yeast Pichia of an active human alanyl-tRNA synthetase. The N-terminal 498 amino acids of the 968-residue polypeptide have substantial (41%) identity with the E. coli protein. A closely related region encompasses the class-defining domain of the E. coli enzyme and includes the part needed for recognition of the acceptor helix. As a result, previously reported mutagenesis, modeling, domain organization, and biochemical characterization on the E. coli protein appear valid as a template for the human protein. In particular, we show that both the E. coli enzyme and the human enzyme purified from Pichia aminoacylate 9-base pair RNA duplexes whose sequences are based on the acceptor stems of either E. coli or human alanine tRNAs. In contrast, the sequences of the two enzymes completely diverge in an internal portion of the C-terminal half that is essential for tetramer formation by the E. coli enzyme, but that is dispensable for microhelix aminoacylation. This divergence correlates with the expressed human enzyme behaving as a monomer. Thus, the region of close sequence similarity may be a consequence of strong selective pressure to conserve the acceptor helix G3:U70 base pair as an RNA signal for alanine. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NIA,ARTHRIT & RHEUMATISM BRANCH,CONNECT TISSUE DIS SECT,BETHESDA,MD 20892. RP SHIBA, K (reprint author), JAPANESE FDN CANC RES,INST CANC,DEPT CELL BIOL,TOSHIMA KU,TOKYO 170,JAPAN. RI Noda, Tetsuo/B-1667-2016 FU NIGMS NIH HHS [GM 15539] NR 67 TC 31 Z9 32 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 22 PY 1995 VL 34 IS 33 BP 10340 EP 10349 DI 10.1021/bi00033a004 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR467 UT WOS:A1995RR46700004 PM 7654687 ER PT J AU SCHWALBE, RA COE, JE NELSESTUEN, GL AF SCHWALBE, RA COE, JE NELSESTUEN, GL TI ASSOCIATION OF RAT C-REACTIVE PROTEIN AND OTHER PENTRAXINS WITH RAT LIPOPROTEINS CONTAINING APOLIPOPROTEIN-E AND APOLIPOPROTEIN-A1 SO BIOCHEMISTRY LA English DT Article ID AMYLOID-P COMPONENT; PHOSPHORYLCHOLINE-BINDING PROTEIN; HAMSTER FEMALE PROTEIN; COMPLEMENT C4B-BINDING PROTEIN; LOW-DENSITY LIPOPROTEINS; SYRIAN-HAMSTER; SERUM-LIPOPROTEINS; ALZHEIMER-DISEASE; HEPARIN; RABBIT AB C-Reactive protein (CRP) is a member of the pentraxin family of proteins, ubiquitous components of animal serum, This study suggests that, in serum, rat CRP is complexed with lipoprotein and may interact directly with apolipoprotein E. When mixed with diluted rat serum, radiolabeled rat CRP showed a slightly higher sedimentation coefficient (about 15%) than that of the free protein. Elimination of calcium or addition of O-phosphorylethanolamine (O-PE), a low molecular weight compound that binds tightly to rat CRP in a calcium-dependent manner, abolished this difference, Adsorption of rat serum on a rat CRP affinity gel and elution with PE resulted in the isolation of material containing high levels of apolipoproteins E and Al. The affinity-purified preparation interacted with rat CRP and altered the sedimentation coefficient of the latter to the value observed in whole serum. Conversely, rat CRP increased the sedimentation coefficient of the major component of the affinity-purified material to that of rat CRP in rat serum (about a 1.8-fold increase), When added to the affinity-purified material or to diluted rat serum, human serum amyloid P (SAP) and hamster female protein (FP), two other members of the pentraxin protein family, also had slightly higher sedimentation coefficients. In contrast, human CRP showed no evidence of an interaction in rat serum or with the affinity-purified proteins, This selectivity coincided with the ability of these pentraxins to bind to O-PE with high affinity, The sedimentation properties of serum lipoproteins, radiolabeled with [H-3]cholesterol, also suggested an interaction with rat CRP. Purified human apolipoprotein E interacted with rat CRP in a calcium-dependent manner that was inhibited by O-PE. These results indicated that rat CRP was associated with lipoproteins in serum and that the interaction may be achieved through apolipoprotein E. Association of pentraxins with lipoproteins may suggest possible functions for pentraxins in normal situations and may be important for certain pathological states, where some of the pentraxins as well as some lipoproteins have been implicated in the pathogenesis of amyloidosis. C1 UNIV MINNESOTA,DEPT BIOCHEM,ST PAUL,MN 55108. NIAID,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. FU NHLBI NIH HHS [HL 15728] NR 57 TC 10 Z9 10 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 22 PY 1995 VL 34 IS 33 BP 10432 EP 10439 DI 10.1021/bi00033a015 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR467 UT WOS:A1995RR46700015 PM 7544614 ER PT J AU BHAT, MK MCPHIE, P TING, YT ZHU, XG CHENG, SY AF BHAT, MK MCPHIE, P TING, YT ZHU, XG CHENG, SY TI STRUCTURE OF THE CARBOXY-TERMINAL REGION OF THYROID-HORMONE NUCLEAR RECEPTORS AND ITS POSSIBLE ROLE IN HORMONE-DEPENDENT INTERMOLECULAR INTERACTIONS SO BIOCHEMISTRY LA English DT Article ID CONFORMATIONAL-CHANGES; BINDING DOMAIN; C-ERBA; MONOCLONAL-ANTIBODIES; SECONDARY STRUCTURE; LIGAND-BINDING; PROTEIN; DNA; RESISTANCE; GENE AB The thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors. To understand the molecular basis of ligand-dependent transactivation, we studied the structure of their carboxyterminal activation domain. We analyzed the structures of the peptides derived from the C-terminal sequences of human TR subtypes beta 1 (h-TR beta 1) and alpha 1 (h-TR alpha 1) and a human TR mutant, PV, by circular dichroism (CD). Mutant PV has a C-terminal frameshift mutation and does not bind to the thyroid hormone, 3,3',5-triiodo-L-thyronine (T-3) Analyses of the secondary structures of the peptides by CD indicate that five amino acids, EVFED, are part of an amphipathic alpha-helix which is required to maintain the structural integrity of the hormone binding domain. A monoclonal antibody, C4 (mAb C4), which recognizes both h-TR beta 1 and h-TR alpha 1 was developed. Using a series of truncated mutants and synthetic peptides, we mapped the epitope of mAb C4 to the conserved C-terminal amino acids, EVFED. Analysis of the binding data indicates that binding of T-3 to either h-TR beta 1 or h-TR alpha 1 was competitively inhibited by mAb C4. Deletion of C-terminal amino acids including EVFED led to a total loss of T-3 binding activity. Thus, part of the T-3 binding site is located in this five amino acid segment. T-3 may transduce its hormonal signal to the transcriptional machinery via interaction with EVFED at the C-terminus of TRs. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 39 TC 29 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 22 PY 1995 VL 34 IS 33 BP 10591 EP 10599 DI 10.1021/bi00033a034 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR467 UT WOS:A1995RR46700034 PM 7544615 ER PT J AU WISTOW, G GRAHAM, C AF WISTOW, G GRAHAM, C TI THE DUCK GENE FOR ALPHA-B-CRYSTALLIN SHOWS EVOLUTIONARY CONSERVATION OF DISCRETE PROMOTER ELEMENTS BUT LACKS HEAT AND OSMOTIC SHOCK RESPONSE SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE CRYSTALLIN; GENE; PROMOTER; EVOLUTION; HEAT SHOCK; STRESS ID NIH 3T3 FIBROBLASTS; HUMAN GLIOMA-CELLS; EXPRESSION; LENS; MOUSE; PROTEINS; SEQUENCE; STRESS; TRANSCRIPTION; CHICKEN AB The gene for alpha B-crystallin from a bird (the domestic duck, Anas platyrhynchos) has been cloned and sequenced to allow comparison with its mammalian homologues. The duck gene has the same general structure as those of humans and rodents although, unlike those of mammals, the duck gene has two polyadenylation signals at the 3' end. The most interesting comparisons are in the 5' flanking promoter regions. In contrast to the broad conservation of promoter sequence among mammals, only two significant blocks and a few smaller elements have been conserved during evolution in the more distantly related avian gene. Block 1 (-350/-308) corresponds to alpha BE-2, a functional element defined in the mouse gene. Further downstream, block 2 (-98/-65) shows 27/33 identity among all three species but does not correspond to any previously defined element. Other regions are less well-conserved. In particular, putative heat-shock response elements of the mammalian alpha B-crystallin genes are absent from the duck gene. In contrast to the heat and osmotic stress-inducibility of mouse alpha B-crystallin in NIH 3T3 cells, duck alpha B-crystallin showed no inducibility in duck cells in culture. Thus, although high expression in lens is common to alpha B-crystallin genes in birds and mammals, other modes of expression appear to be taxon-specific. RP NEI, MOLEC STRUCT & FUNCT SECT, LMDB, BETHESDA, MD 20892 USA. NR 48 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD AUG 22 PY 1995 VL 1263 IS 2 BP 105 EP 113 DI 10.1016/0167-4781(95)00087-W PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RT046 UT WOS:A1995RT04600001 PM 7640300 ER PT J AU YANG, HK LINNOILA, RI CONRAD, NK KRASNA, MJ AISNER, SC JOHNSON, BE KELLEY, MJ AF YANG, HK LINNOILA, RI CONRAD, NK KRASNA, MJ AISNER, SC JOHNSON, BE KELLEY, MJ TI TP53 AND RAS MUTATIONS IN METACHRONOUS TUMORS FROM PATIENTS WITH CANCER OF THE UPPER AERODIGESTIVE TRACT SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CELL LUNG-CANCER; P53 GENE-MUTATIONS; BLADDER-CANCER; CARCINOMA; STAGE; LINES; HEAD AB Patients who initially develop an upper aerodigestive tract cancer have an increased risk of second primary cancers. We examined TP53 and RAS mutations and p53 protein in 21 tumors from 10 patients with upper aerodigestive tract cancer who developed a metachronous tumor, to assess the genetic changes that occur in multiple primary tumors from the same individual. Thirteen of 21 (62%) tumors were found to have mis-sense mutations of either TP53 or RAS. Six tumors had TP53 mutations in codons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K-RAS. Only one patient had concordance of a mutation in 2 tumors; this mutation occurred in K-RAS and was accompanied by discordance of TP53 mutation. Three patients had tumors discordant for both TP53 and RAS mutations. Smoking-related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and transitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohistochemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations are discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, supporting the concept that these cancers arise independently. (C) 1995 Wiley-Liss, Inc. C1 NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. NCI,BIOMARKERS & PREVENT RES BRANCH,BETHESDA,MD 20889. UNIV MARYLAND HOSP,DEPT SURG,BALTIMORE,MD 21201. UNIV MARYLAND HOSP,DEPT PATHOL,BALTIMORE,MD 21201. RI Yang, Han-Kwang/J-2767-2012; OI Kelley, Michael/0000-0001-9523-6080 NR 27 TC 27 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 22 PY 1995 VL 64 IS 4 BP 229 EP 233 DI 10.1002/ijc.2910640403 PG 5 WC Oncology SC Oncology GA RT350 UT WOS:A1995RT35000002 PM 7657384 ER PT J AU IACANGELO, AL EIDEN, LE AF IACANGELO, AL EIDEN, LE TI CHROMOGRANIN-A - CURRENT STATUS AS A PRECURSOR FOR BIOACTIVE PEPTIDES AND A GRANULOGENIC/SORTING FACTOR IN THE REGULATED SECRETORY PATHWAY SO REGULATORY PEPTIDES LA English DT Review ID RAT ADRENAL-MEDULLA; PARATHYROID CELL SECRETION; B SECRETOGRANIN-I; A MESSENGER-RNA; INHIBITS INSULIN-SECRETION; RIBONUCLEIC-ACID LEVELS; CENTRAL NERVOUS-SYSTEM; N-TERMINAL FRAGMENT; BASIC AMINO-ACIDS; CHROMAFFIN GRANULES C1 NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. OI Eiden, Lee/0000-0001-7524-944X NR 175 TC 126 Z9 127 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 22 PY 1995 VL 58 IS 3 BP 65 EP 88 DI 10.1016/0167-0115(95)00069-N PG 24 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RR998 UT WOS:A1995RR99800001 PM 8577930 ER PT J AU FREED, C REVAY, R VAUGHAN, RA KRIEK, E GRANT, S UHL, GR KUHAR, MJ AF FREED, C REVAY, R VAUGHAN, RA KRIEK, E GRANT, S UHL, GR KUHAR, MJ TI DOPAMINE TRANSPORTER IMMUNOREACTIVITY IN RAT-BRAIN SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CATECHOLAMINE; COCAINE; PARKINSONS DISEASE; STRIOSOMES; SUBSTANTIA NIGRA ID PARKINSONS-DISEASE; MIDBRAIN NEURONS; MESSENGER-RNA; EXPRESSION; CLONING; NEUROTRANSMITTER; STRIATUM; SITES AB The dopamine transporter (DAT) is a primary site for the action of cocaine in inducing euphoria. Its action is necessary for the selectivities of dopaminergic neurotoxins that provide the best current experimental models of Parkinson's disease. In the present report, rat dopamine transporter-like immunoreactivity (iDAT) was assessed by immunohistochemistry using newly developed polyclonal antisera raised against conjugated peptides corresponding to sequences found in the dopamine transporter's carboxy- and amino-termini. Dense iDAT was observed in patterns consistent with neural processes and terminals in the striatum, nucleus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula. Perikarya in the substantia nigra pars compacta were immunostained with moderate intensity using one of two immunohistochemical methods, while scattered ventral tegmental area perikarya were stained with somewhat less intensity. Immunoreactive neuronal processes with axonal and dendritic morphologies were stained in the substantia nigra and the paranigral and parabrachialis pigmentosus nuclei of the ventral tegmental area, while sparser processes were noted more medially in the ventral tegmental area. Neuronal processes were found in several laminae in the cingulate cortex, with notable fiber densities in the superficial aspects of lamina I and laminae II/III. The intensities of immunoreactivities in striatum and cerebral cortex were dramatically attenuated ipsilateral to nigrostriatal bundle B-hydroxydopamine lesions. Specificity of immunostaining was supported by agreement of the results using sera directed against two distinct DAT segments, studies with preimmune and preadsorbed sera and studies of the extracted protein. These antisera identify and reveal details of the distribution of DAT immunoreactivity in rat brain and display variations in levels of DAT expression of likely functional significance. (C) 1995 Wiley-Liss, Inc. C1 NIDA,MOLEC NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. NIDA,NEUROSCI BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. UNIV COLORADO,SCH MED,DEPT PHARMACOL,DIV CLIN PHARMACOL,DENVER,CO 80262. UNIV COLORADO,SCH MED,DEPT MED,DENVER,CO 80262. UNIV DELAWARE,DEPT PSYCHOL,NEWARK,DE 19716. FU NINDS NIH HHS [NS18639, NS23918] NR 23 TC 151 Z9 152 U1 1 U2 10 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 AUG 21 PY 1995 VL 359 IS 2 BP 340 EP 349 DI 10.1002/cne.903590211 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RQ593 UT WOS:A1995RQ59300010 PM 7499533 ER PT J AU CASSMAN, M AF CASSMAN, M TI NIH SUPPORT SO SCIENTIST LA English DT Letter RP CASSMAN, M (reprint author), NATL INST GEN MED SCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD AUG 21 PY 1995 VL 9 IS 16 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA RQ478 UT WOS:A1995RQ47800010 ER PT J AU BEUTLER, JA CARDELLINA, JH SHOEMAKER, RH BOYD, MR AF BEUTLER, JA CARDELLINA, JH SHOEMAKER, RH BOYD, MR TI NOVEL CYTOTOXIC SAPONINS FROM A TROPICAL PLANT SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 2 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600002 ER PT J AU HABERMAN, CB AF HABERMAN, CB TI THE TEHIP GOPHER - BOOKMARK FOR TOXICOLOGY AND ENVIRONMENTAL-HEALTH INFORMATION ON THE INTERNET SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 13 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600896 ER PT J AU ISSAQ, HJ CHANG, KC MUSCHIK, GM AF ISSAQ, HJ CHANG, KC MUSCHIK, GM TI HIGH-SENSITIVITY FLUORESCENCE DETECTION IN CAPILLARY ELECTROPHORESIS USING KRF LASER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 19 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600367 ER PT J AU MILNE, GWA NICKLAUS, MC WANG, SM AF MILNE, GWA NICKLAUS, MC WANG, SM TI USE OF 3D PHARMACOPHORE SEARCHING IN DRUG LEAD DISCOVERY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 20 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600939 ER PT J AU WANG, SM NICKLAUS, MC MILNE, GWA YAN, XJ RICE, WG AF WANG, SM NICKLAUS, MC MILNE, GWA YAN, XJ RICE, WG TI BINDING MODES OF NOVEL HIV PROTEASE INHIBITORS BY MOLECULAR MODELING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 21 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600940 ER PT J AU NICKLAUS, MC POMMIER, Y MAZUMDER, A AF NICKLAUS, MC POMMIER, Y MAZUMDER, A TI HIV-1 INTEGRASE INHIBITORS - 3D SEARCHING AND ACTIVE-SITE DOCKING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 22 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600941 ER PT J AU ZHANG, HP FORD, H KELLEY, JA AF ZHANG, HP FORD, H KELLEY, JA TI MEASUREMENT OF INTRACELLULAR 2'-FLUORO-2',3'-DIDEOXYADENOSINE-5'-TRIPHOSPHATE, THE ACTIVE METABOLITE OF A NEW ANTI-AIDS DRUG SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 45 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600393 ER PT J AU KALBERER, BR AF KALBERER, BR TI PUBLIC UNDERSTANDING OF SCIENCE - APPROACHING THE ISSUE FROM THE FEDERAL PERSPECTIVE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,OFF EDUC POLICY,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 55 EP IEC PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25602018 ER PT J AU MILNE, GWA AF MILNE, GWA TI SEARCHING OF LARGE DATABASES OF CHEMICAL-REACTIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 65 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP256 UT WOS:A1995RP25600984 ER PT J AU SAAB, NH DONKOR, IO RODRIGUEZ, L KADOR, PF MILLER, DD AF SAAB, NH DONKOR, IO RODRIGUEZ, L KADOR, PF MILLER, DD TI N-4 SUBSTITUTED PHENYLSULFONYLNITROMETHANE ANALOGS AS POTENT INHIBITORS OF ALDOSE REDUCTASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV TENNESSEE CTR HLTH SCI,DEPT PHARMACEUT SCI,MEMPHIS,TN 38163. NATL EYE INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 71 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900071 ER PT J AU KIESEWETTER, DO LANG, LX LEE, JT PARK, SG PAIK, CH HERSCOVITCH, P CARSON, RC ECKELMAN, WC AF KIESEWETTER, DO LANG, LX LEE, JT PARK, SG PAIK, CH HERSCOVITCH, P CARSON, RC ECKELMAN, WC TI SUBTYPE-SELECTIVE MUSCARINIC LIGANDS FOR RECEPTOR IMAGING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 72 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900327 ER PT J AU KOEPKE, MBK ROUZER, CA TANEYHILL, LA SMITH, NA HUGHES, SH BOYER, PL ARNOLD, E DING, JP DAS, K TANTILLO, C KZHANG, WY MICHEJDA, CJ SMITH, RH AF KOEPKE, MBK ROUZER, CA TANEYHILL, LA SMITH, NA HUGHES, SH BOYER, PL ARNOLD, E DING, JP DAS, K TANTILLO, C KZHANG, WY MICHEJDA, CJ SMITH, RH TI MOLECULAR MODELING STUDIES OF HIV-1 REVERSE-TRANSCRIPTASE NONNUCLEOSIDE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. WESTERN MARYLAND COLL,WESTMINSTER,MD 21157. CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. RI Taneyhill, Lisa/K-1815-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 93 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900092 ER PT J AU EZZITOUNI, A SIDDIQUI, MA MARQUEZ, VE AF EZZITOUNI, A SIDDIQUI, MA MARQUEZ, VE TI SYNTHESIS OF CONFORMATIONALLY RIGID CARBOCYCLIC AZT ANALOGS WITH DIFFERENT SUGAR RING PUCKERINGS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 96 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900095 ER PT J AU BURGESS, EM RUELL, JA GRUSZECKAKOWALIK, E ZALKOW, LH HAUGWITZ, R AF BURGESS, EM RUELL, JA GRUSZECKAKOWALIK, E ZALKOW, LH HAUGWITZ, R TI POLYANIONIC CHEMICAL BARRIERS TO HIV-1 BINDING TO CD4 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332. NCI,DRUG SYNTH & CHEM BRANCH,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 100 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900099 ER PT J AU EPSTEIN, JW BIRNBERG, GH FANSHAWE, WJ KAYAKIRI, H RICE, KC ROTHMAN, RB XU, H BECKETTS, K AF EPSTEIN, JW BIRNBERG, GH FANSHAWE, WJ KAYAKIRI, H RICE, KC ROTHMAN, RB XU, H BECKETTS, K TI THE ENANTIOMERS OF 6,6-DIMETHOXY-5-(3-HYDROXYPENYL)-3-METHYL-3-AZABICYCLO-[3.2.0]HEPTANE AND THEIR BINDING-PROPERTIES AT OPIOID RECEPTOR SUBTYPES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 WYETH AYERST RES,PEARL RIVER,NY 10965. NIH,BETHESDA,MD 20892. USN,RES LAB,WASHINGTON,DC 20375. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 161 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900159 ER PT J AU GUPTA, PK BLUMBERGS, P VARMA, RK AF GUPTA, PK BLUMBERGS, P VARMA, RK TI SYNTHETIC ANALOG OF SESBANIMIDE AND ITS ANTICANCER ACTIVITY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ASH STEVENS INC,DETROIT,MI 48202. NCI,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 188 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900186 ER PT J AU JAIN, R COHEN, LA AF JAIN, R COHEN, LA TI REGIOSPECIFIC ALKYLATION OF HISTIDINE AND HISTAMINE AT N-1 (TAU) AND ANTIMALARIAL ACTIVITIES OF THE ANALOGS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 217 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900215 ER PT J AU JAIN, R COHEN, LA AF JAIN, R COHEN, LA TI RADICAL C-CYCLOALKYLATION OF HISTIDINE, HISTAMINE AND OTHER AZAHETEROAROMATIC SYSTEMS AS A ROUTE TO POTENTIAL MEDICINAL AGENTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 226 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900224 ER PT J AU BUOLAMWINI, JK WEINSTEIN, JN PATERSON, ARP AF BUOLAMWINI, JK WEINSTEIN, JN PATERSON, ARP TI MOLECULAR MODELING STUDIES ON SAENTA-FLUORESCEIN CONJUGATES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract ID NUCLEOSIDE TRANSPORTER C1 UNIV MISSISSIPPI,SCH PHARM,DEPT MED CHEM,UNIVERSITY,MS 38677. NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. UNIV ALBERTA,DEPT PHARMACOL,EDMONTON,AB T6G 2H7,CANADA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 234 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900232 ER PT J AU BARCHI, JJ JEONG, LS SIDDIQUI, M MARQUEZ, VE AF BARCHI, JJ JEONG, LS SIDDIQUI, M MARQUEZ, VE TI NMR AND PSEUDOROTATIONAL ANALYSIS OF FLUORINATED OXONUCLEOSIDES AND THIODIDEOXYNUCLEOSIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 243 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25900241 ER PT J AU OIE, T HUTCHINS, CW TOPOL, IA BURT, SK AF OIE, T HUTCHINS, CW TOPOL, IA BURT, SK TI QUANTUM-MECHANICAL STUDIES OF REACTION-MECHANISMS FOR ASPARTIC PROTEASES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ABBOTT LABS,ABBOTT PK,IL 60064. NCI,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 20 PY 1995 VL 210 BP 337 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA RP259 UT WOS:A1995RP25901251 ER PT J AU KAWASE, M MOMOEDA, M YOUNG, NS KAJIGAYA, S AF KAWASE, M MOMOEDA, M YOUNG, NS KAJIGAYA, S TI MOST OF THE VP1 UNIQUE REGION OF B19 PARVOVIRUS IS ON THE CAPSID SURFACE SO VIROLOGY LA English DT Article ID PARTICLES; HYBRID; IMMUNOGENICITY; POLIOVIRUS; ANTIGEN; EXPRESSION; INFECTION; CHIMERAS; EPITOPES; PROTEIN AB B19 parvovirus is pathogenic in man and a vaccine is desirable. In convalescence after acute infection, the dominant humoral immune response is directed to the minor capsid protein called VP1, which differs from the major capsid protein by an additional NH2-terminal 227 amino acids. We have previously shown that this unique region contains multiple linear neutralizing epitopes. We produced seven recombinant B19 capsids that contained progressively truncated VP1 unique region sequences, each fused to a Flag peptide (AspTyrLysAspAspAspAspLys) at the NH2-terminus. Capsids containing normal VP2 and truncated Flag-VP1 proteins and, in some cases, only truncated Flag-VP1 chimeric proteins, were analyzed by ELISA, affinity chromatography, and electron microscopy using anti-flag monoclonal antibody. All regions examined showed binding to anti-flag antibody in multiple assays, indicating that most of the VP1 unique region is external to the capsid and accessible to antibody binding. These results have implications for the design of a B19 parvovirus vaccine and the use of empty capsids for presentation of heterologous protein antigens. (C) 1995 Academic Press, Inc. C1 NHLBI,HEMATOL BRANCH,ROCKVILLE,MD 20892. NR 26 TC 35 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 20 PY 1995 VL 211 IS 2 BP 359 EP 366 DI 10.1006/viro.1995.1418 PG 8 WC Virology SC Virology GA RQ607 UT WOS:A1995RQ60700001 PM 7544049 ER PT J AU SARAFI, TR MCBRIDE, AA AF SARAFI, TR MCBRIDE, AA TI DOMAINS OF THE BPV-1 E1 REPLICATION PROTEIN REQUIRED FOR ORIGIN-SPECIFIC DNA-BINDING AND INTERACTION WITH THE E2 TRANSACTIVATOR SO VIROLOGY LA English DT Article ID BOVINE PAPILLOMAVIRUS TYPE-1; TRANSCRIPTIONAL ACTIVATOR; TRANSIENT REPLICATION; PHOSPHOPROTEIN; POLYPEPTIDES; INVITRO; SITE; PHOSPHORYLATION; IDENTIFICATION; SEQUENCES AB The viral E1 and E2 proteins are required for replication of bovine papillomavirus type 1 DNA. Both proteins bind as a complex to the replication origin, which consists of an El binding site flanked on either side by E2 binding sites. The E1 protein has properties common to replication initiator proteins such as sequence-specific origin binding and DNA helicase activities. The E2 protein is a transcriptional transactivator that forms a complex with the E1 protein and enhances binding of E1 to the replication origin. We have mapped the regions of the E1 protein required for sequence-specific DNA binding, for cooperative binding with the E2 protein to the origin region, and for interaction with the E2 protein. These studies demonstrate that a region between amino acids 162 and 378 of the E1 protein is important for origin-specific DNA binding. The C-terminal half of the E1 protein is required in addition to the DNA binding domain (residues 162 to 605) for cooperative binding to the origin with the E2 protein. Binding studies confirmed that this region is also required for efficient complex formation with the E2 protein. (C) 1995 Academic Press, Inc. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. OI McBride, Alison/0000-0001-5607-5157 NR 34 TC 54 Z9 54 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 20 PY 1995 VL 211 IS 2 BP 385 EP 396 DI 10.1006/viro.1995.1421 PG 12 WC Virology SC Virology GA RQ607 UT WOS:A1995RQ60700004 PM 7645243 ER PT J AU DEVICO, AL RAHMAN, R WELCH, J CROWLEY, R LUSSO, P SARNGADHARAN, MG PAL, R AF DEVICO, AL RAHMAN, R WELCH, J CROWLEY, R LUSSO, P SARNGADHARAN, MG PAL, R TI MONOCLONAL-ANTIBODIES RAISED AGAINST COVALENTLY CROSS-LINKED COMPLEXES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 AND CD4 RECEPTOR IDENTIFY A NOVEL COMPLEX-DEPENDENT EPITOPE ON GP120 SO VIROLOGY LA English DT Note ID SOLUBLE CD4; ENVELOPE GLYCOPROTEIN; EXTERNAL GLYCOPROTEIN; HTLV-III/LAV; BINDING; HIV-1; NEUTRALIZATION; CELLS; INFECTION; PROTEIN AB The binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120, to its cell surface receptor, CD4, represents a molecular interaction involving distinct alterations in protein structure. Consequently, the pattern of epitopes presented on the gp120-CD4 complex should differ from those on free gp120. To investigate this concept, mice were immunized with covalently crosslinked complexes of viral HIV-1(IIIB) gp120 and soluble CD4. Two monoclonal antibodies (MoAbs) obtained from the immunized mice exhibited a novel epitope specificity. The MoAbs were marginally reactive with HIV-1(IIIB) gp120, highly reactive with gp120-CD4 complexes, and unreactive with soluble CD4. The same pattern of reactivity was seen in solid-phase assays using HIV-1(451) gp120. A similar specificity for complexes was evident in flow cytometry experiments, in which MoAb reactivity was dependent upon the attachment of gp120 to CD4-positive cells. In addition, MoAb reactivity was detected upon the interaction of CD4 receptors with purified HIV-1(IIIB) virions. Notably, seroantibodies from HIV-positive individuals competed for MoAb binding, indicating that the epitope is immunogenic in humans. The results demonstrated that crosslinked gp120-CD4 complexes elicit antibodies to cryptic gp120 epitopes that are exposed during infection in response to receptor binding. These findings may have important implications for the consideration of HIV envelope-receptor complexes as targets for virus neutralization. (C) 1995 Academic Press, Inc. C1 ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NCI,BETHESDA,MD 20892. NR 34 TC 32 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 20 PY 1995 VL 211 IS 2 BP 583 EP 588 PG 6 WC Virology SC Virology GA RQ607 UT WOS:A1995RQ60700024 PM 7544051 ER PT J AU LEEHUANG, S HUANG, PL CHEN, HC HUANG, PL BOURINBAIAR, A HUANG, HI KUNG, HF AF LEEHUANG, S HUANG, PL CHEN, HC HUANG, PL BOURINBAIAR, A HUANG, HI KUNG, HF TI ANTI-HIV AND ANTITUMOR ACTIVITIES OF RECOMBINANT MAP30 FROM BITTER-MELON SO GENE LA English DT Article DE MOMORDICA CHARANTIA; RECOMBINANT ANTIVIRAL AGENT; CLONING; EXPRESSION ID HOST-CELL MEMBRANE; INFECTION; MECHANISM; PROTEINS; AGENTS; VIRUS; DNA AB MAP30 is an anti-HIV plant protein that we have identified and purified to homogeneity from bitter melon (Momordica charantia). It is capable of acting against multiple stages of the viral life cycle, on acute infection as well as replication in chronically infected cells. In addition to antiviral action, MAP30 also possesses anti-tumor activity, topological inactivation of viral DNA, inhibition of viral integrase and cell-free ribosome-inactivation activities. We have cloned and expressed the MAP30 gene, The objective of this study is to characterize recombinant MAP30 (re-MAP30) and to determine its anti-HIV, anti-tumor and other activities. We report here that re-MAP30 inhibits HIV-1 and certain human tumors to the same extent as its native counterpart, natural MAP30 (nMAP30). The anti-HIV activity was measured by quantitative focal syncytium formation on CEM-ss cell monolayers, viral core protein p24 expression and viral-associated reverse transcriptase activity in HIV-1-infected H9 cells. The anti-tumor activity was measured by metabolic labeling of protein synthesis in tumor cells. In the dose range of the assay, re-MAP30 exhibits little toxicity to the uninfected viral target cells and other normal human cells. Identical to nMAP30, re-MAP30 is also active in topological inactivation of viral DNA, inhibition of viral DNA integration and cell-free ribosome inactivation. The cloning and expression of the gene encoding biologically active re-MAP30 provides an abundant source of homogeneous material for clinical investigations, as well as structure-function studies of this novel antiviral and anti-tumor agent. C1 NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016. AMER BIOSCI,NEW YORK,NY 10021. NICHHD,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DCT,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL L,FREDERICK,MD 21701. FU NIAID NIH HHS [R01 AI 31334] NR 23 TC 85 Z9 110 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 19 PY 1995 VL 161 IS 2 BP 151 EP 156 DI 10.1016/0378-1119(95)00186-A PG 6 WC Genetics & Heredity SC Genetics & Heredity GA RR667 UT WOS:A1995RR66700002 PM 7665070 ER PT J AU BEEBE, LE FORNWALD, LW ALWORTH, WL DRAGNEV, KH LUBET, RA AF BEEBE, LE FORNWALD, LW ALWORTH, WL DRAGNEV, KH LUBET, RA TI EFFECT OF DIETARY AROCLOR-1254 EXPOSURE ON LUNG AND KIDNEY CYTOCHROMES P450 IN FEMALE RATS - EVIDENCE FOR P4501A2 EXPRESSION IN KIDNEY SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE AROCLOR 1254; CYTOCHROME P450; LUNG; KIDNEY ID POLYCHLORINATED-BIPHENYLS; N-NITROSODIMETHYLAMINE; LIVER-TUMORS; RESPIRATORY-TRACT; MOUSE LUNG; INDUCTION; MICE; DEALKYLATION; ACCUMULATION; HEPATOCYTES AB In this report, we have investigated the effect of dietary exposure to Aroclor 1254 (1-100 ppm) given chronically or discontinuously over an 84-day time interval to the female F344 rat, Cytochrome P4501A was quantified in lung and kidney by measuring the dealkylation of ethoxyresorufin substrate and by Western immunoblotting. P4501A displayed a dose- and time-dependent increase in both extrahepatic organs. The kidney appeared to be more responsive to induction than lung at all doses (maximum of 500-fold induction following 84 days exposure to 100 ppm), Further, there was evidence by enzymatic activity, immunoblotting and Northern analysis of total RNA for the presence of 1A2 in the most highly induced kidneys, The decline in 1A induction observed following discontinuous exposure was more prominent in the kidney than in the lung, These data demonstrate the sensitivity of kidney to P4501A induction capacity as compared to lung, although the persistence of the induction response was evident in lung and not kidney. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. TULANE UNIV,DEPT CHEM,NEW ORLEANS,LA 70118. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP BEEBE, LE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 31 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCI PUBL 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 AUG 18 PY 1995 VL 97 IS 3 BP 215 EP 227 DI 10.1016/0009-2797(95)03617-U PG 13 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA RX557 UT WOS:A1995RX55700002 PM 7671339 ER PT J AU POLZER, RJ COFFING, SL MARCUS, CB PARK, SS GELBOIN, HV BAIRD, WM AF POLZER, RJ COFFING, SL MARCUS, CB PARK, SS GELBOIN, HV BAIRD, WM TI INHIBITION OF BENZO[A]PYRENE METABOLISM BY INSULIN, FITC-INSULIN AND AN FITC-INSULIN-ANTIBODY CONJUGATE IN THE HUMAN HEPATOMA-CELL LINE HEPG2 SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE INSULIN; FLUORESCEIN ISOTHIOCYANATE INSULIN; HEPG2 HUMAN HEPATOMA CELL LINE; BENZO[A]PYRENE METABOLISM ID HUMAN CYTOCHROME-P-450 ENZYMES; MONOCLONAL-ANTIBODIES; MAMMALIAN-CELLS; INDUCTION; BENZO(A)PYRENE; MACROMOLECULES; ACTIVATION; CHEMICALS; RECEPTOR; PROTEINS AB Benzo[a]pyrene (BaP) can be metabolically activated to an ultimate carcinogen, (+)-anti-BaP-7, 8-dihydrodiol-9,10-epoxide [(+)-anti-BaPDE] by cells in culture. This activation involves oxidation by specific isoforms of cytochrome P450s such as CYP1A1. The human hepatoma cell line, HepG2, was used to examine the effect of inhibition of CYP1A1 activity by anti CYP1A1 specific antibodies on BaP metabolism. Metabolism of BaP to water-soluble metabolites by HepC2 cells in culture was 50% lower in fluorescein isothiocyanate (FITC)-insulin-CYP1A1-antibody-conjugate-treated cells than in control cells. However, FITC-insulin (lacking anti CYP1A1 conjugates) or insulin alone also decreased BaP metabolism by 50%. This insulin-induced inhibition of BaP metabolism was observed for cultures treated with a concentration range of FITC-insulin from 50-1000 nM. FITC-conjugated gamma-globulin showed no significant binding to HepG2 cells by fluorescence microscopy, however, FITC-insulin-antibody conjugates bound extensively, suggesting that FITC-insulin conjugates still retain the ability to bind insulin receptors. These results demonstrate that free insulin, FITC-insulin or FITC-insulin conjugated to antibodies are effective inhibitors of BaP metabolism in cells in culture. C1 PURDUE UNIV,DEPT PHARMACOL & TOXICOL,W LAFAYETTE,IN 47907. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP POLZER, RJ (reprint author), PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,HANSEN LIFE SCI RES BLDG,W LAFAYETTE,IN 47907, USA. FU NCI NIH HHS [CA40228]; NIEHS NIH HHS [ES05311] NR 41 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCI PUBL 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 AUG 18 PY 1995 VL 97 IS 3 BP 307 EP 318 DI 10.1016/0009-2797(95)03640-8 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA RX557 UT WOS:A1995RX55700010 PM 7671346 ER PT J AU SUN, Y HEGAMYER, G KIM, HT SITHANANDAM, K LI, H WATTS, R COLBURN, NH AF SUN, Y HEGAMYER, G KIM, HT SITHANANDAM, K LI, H WATTS, R COLBURN, NH TI MOLECULAR-CLONING OF MOUSE-TISSUE INHIBITOR OF METALLOPROTEINASES-3 AND ITS PROMOTER - SPECIFIC LACK OF EXPRESSION IN NEOPLASTIC JB6 CELLS MAY REFLECT ALTERED GENE METHYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; NASOPHARYNGEAL CARCINOMA; POINT MUTATION; MESSENGER-RNA; PHORBOL ESTER; BINDING-SITE; LIVER CELLS; HA-RAS; TRANSFORMATION; P53 AB Mouse tissue inhibitor of metalloproteinases-3 (mTIMP-3), a gene specifically not expressed in neoplastic JB6 cells, has been isolated recently through the use of the mRNA differential display technique (Sun, Y., Hegamyer, G., and Colburn, N. H. (1994) Cancer Res. 54, 1139-1144). We report here the full-length mTIMP-3 cDNA sequence, the promoter sequence and partial characterization, expression and induction of TIMP-3, and the possible molecular basis for the lack of mTIMP-3 expression in neoplastic JB6 cells. There are three transcripts arising from alternative polyadenylation of mouse TIMP-3 gene, having sizes of 4.6, 2.8, and 2.3 kilobase pairs, respectively. All three TIMP-3 transcripts are expressed in preneoplastic but not neoplastic JB6 cells. Computer analysis of cloned TIMP-3 promoter revealed six AP-1 binding sites, two NF-kappa B sites, a c-Myc site, and two copies of a p53 binding motif separated by eight base pairs with two mismatches at the second motif, along with many other cis elements, TIMP-3 gene expression was inducible by AP-1 and NF-kappa B activators, 12-O-tetradecanoylphorbol-13-acetate, and tumor necrosis factor-alpha only in preneoplastic cells with an induction peak at 2 h post-treatment, suggesting classification of mTIMP-3 as a member of the immediate early gene family. Southern blot, mutational analysis, and transient transcriptional activation experiments revealed that the lack of expression of mTIMP-3 in neoplastic JB6 cells was due neither to gross deletion nor to promoter mutation of the gene, nor was there a lack of transcription factors required for transcriptional activation. Instead, the lack of TIMP-3 expression in neoplastic JB6 cells may reflect an abnormal methylation of the gene. Both hyper- and hypomethylation of the mTIMP-3 gene are associated with complete down-regulation of gene expression in neoplastic JB6 cell lines. Treatment of neoplastic cells with the methylase inhibitor 5-azacytidine caused reexpression of the mTIMP-3 gene in a tumor cell line that showed hypermethylation but not in another that showed hypomethylation of the gene, suggesting a complex role for methylation in the silencing of gene expression. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYN CORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV P,FREDERICK,MD 21702. RP SUN, Y (reprint author), PARKE DAVIS PHARMACEUT RES,DEPT CANC RES,2800 PLYMOUTH RD,ANN ARBOR,MI 48105, USA. NR 59 TC 68 Z9 71 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 1995 VL 270 IS 33 BP 19312 EP 19319 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300021 PM 7642607 ER PT J AU YOKOMIZO, A KOHNO, K WADA, M ONO, M MORROW, CS COWAN, KH KUWANO, M AF YOKOMIZO, A KOHNO, K WADA, M ONO, M MORROW, CS COWAN, KH KUWANO, M TI MARKEDLY DECREASED EXPRESSION OF GLUTATHIONE-S-TRANSFERASE-PI GENE IN HUMAN CANCER CELL-LINES RESISTANT TO BUTHIONINE SULFOXIMINE, AN INHIBITOR OF CELLULAR GLUTATHIONE SYNTHESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN OVARIAN-CANCER; DNA TOPOISOMERASE-II; ELECTROPHILE-RESPONSIVE ELEMENT; YA-SUBUNIT GENE; CHEMICAL CARCINOGENS; NUCLEOTIDE-SEQUENCE; DRUG ACCUMULATION; ALKYLATING-AGENTS; ESCHERICHIA-COLI; MESSENGER-RNA AB Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits an enzyme, gamma-glutamyl-cysteine synthetase (gamma-GCS), which is a critical step in glutathione biosynthesis. We isolated three BSO-resist ant sublines, KB/BSO1, KB/BSO2, and KB/BSO3, from human epidermoid cancer KB cells. These cell lines showed 10-to 13-fold higher resistance to BSO, respectively, and had collateral sensitivity to cisplatin, ethacrynic acid, and alkylating agents such as melphalan and nitrosourea. Cellular levels of glutathione S-transferase pi (GST-pi) and its mRNA in BSO-resistant cell lines were less than 10% of the parental cells, Nuclear run-on assay showed that the transcriptional activity of GST-pi was decreased in BSO-resistant cells, and transient transfection of GST-pi promoter-chloramphenicol acetyltransferase constructs revealed that the sequences between -130 and -80 base pairs of the 5'-flanking region were at least partially responsible for the decreased expression of the GST-pi gene. By contrast, gamma-GCS mRNA levels were 3-to 5-fold higher in resistant cell lines than in KB cells, and the gamma-GCS gene was found to be amplified in the BSO-resistant cell lines. GST-pi mRNA levels appeared to be inversely correlated with gamma-GCS mRNA levels in BSO-resistant cells. We further established the transfectants, KB/BSO3-pi 1 and KB/BSO3-pi 2, that overexpressed GST-pi; from KB/BSO3, after introducing a GST-pi expression plasmid. These two transfectants had similar levels in gamma-GCS mRNA, drug sensitivity to alkylating agents, and glutathione content as those of KB cells. These findings suggest that the cellular levels of GST-pi and gamma-GCS might be co-regulated in these novel BSO-resistant cells. C1 KYUSHU UNIV,SCH MED,DEPT BIOCHEM,FUKUOKA 81282,JAPAN. WAKE FOREST UNIV,MED CTR,DEPT BIOCHEM,WINSTON SALEM,NC 27157. NCI,MED BRANCH,BETHESDA,MD 20892. NR 60 TC 32 Z9 35 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 1995 VL 270 IS 33 BP 19451 EP 19457 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300042 PM 7642628 ER PT J AU BEBENEK, K BEARD, WA CASASFINET, JR KIM, HR DARDEN, TA WILSON, SH KUNKEL, TA AF BEBENEK, K BEARD, WA CASASFINET, JR KIM, HR DARDEN, TA WILSON, SH KUNKEL, TA TI REDUCED FRAMESHIFT FIDELITY AND PROCESSIVITY OF HIV-1 REVERSE-TRANSCRIPTASE MUTANTS CONTAINING ALANINE SUBSTITUTIONS IN HELIX-H OF THE THUMB SUBDOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; DNA; MISALIGNMENT; TERMINATION; POLYMERASE; MECHANISM; TEMPLATE AB We have analyzed two human immunodeficiency virus (HIV-1) reverse transcriptase mutants of helix H in the thumb subdomain suggested by x-ray crystallography to interact with the primer strand of the template-primer. These enzymes, G262A and W266A, were previously shown to have greatly elevated dissociation rate constants for template-primer and to be much less sensitive to inhibition by 3'-azidodeoxythymidine 5'-triphosphate. Here we describe their processivity and error specificity. The results reveal that: (i) both enzymes have reduced processivity and lower fidelity for template-primer slippage errors, (ii) they differ from each other in sequence dependent termination of processive synthesis and in error specificity, and (iii) the magnitude of the mutator effect relative to wild-type enzyme for deletions in homopolymeric sequences decreases as the length of the run increases. Thus amino acid substitutions in a subdomain thought to interact with the duplex template-primer confer a strand slippage mutator phenotype to a replicative DNA polymerase. This suggests that interactions between specific amino acids and the primer stem at positions well removed from the active site are critical determinants of processivity and fidelity. These effects, obtained in aqueous solution during catalytic cycling, are consistent with and support the existing crystallographic structural model. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,QUANTITAT & COMP BIOL LAB,RES TRIANGLE PK,NC 27709. UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX 77555. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 25 TC 107 Z9 107 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 1995 VL 270 IS 33 BP 19516 EP 19523 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300051 PM 7543900 ER PT J AU LIU, J SCHONEBERG, T VANRHEE, M WESS, J AF LIU, J SCHONEBERG, T VANRHEE, M WESS, J TI MUTATIONAL ANALYSIS OF THE RELATIVE ORIENTATION OF TRANSMEMBRANE HELIX-I AND HELIX-VII IN G-PROTEIN-COUPLED RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTAGONIST BINDING; IDENTIFICATION; ACETYLCHOLINE; GENES; SELECTIVITY; EXPRESSION; RHODOPSIN; AGONIST; DOMAINS; DNA AB Currently, detailed structural information about the arrangement of the seven transmembrane helices (TM I-VII) present in all G protein-coupled receptors is still lacking. We demonstrated previously that hybrid m2/m5 muscarinic acetylcholine receptors which contain m5 sequence in TRI I and m2 sequence in TM VII were unable to bind significant amounts of muscarinic radioligands (Pittel, Z., and Wess, J. (1994) Mol. Pharmacol. 45, 61-64). By using immunocytochemical and enzyme-linked immunosorbent assay techniques, we show in the present study that these pharmacologically inactive mutant receptors are present (at high levels) on the surface of transfected COS-7 cells. Strikingly, all misfolded m2/m5 hybrid receptors could be pharmacologically rescued by introduction of a single point mutation into either TM I (m5Thr(37) --> m2Ala(30)) or TM VII (m2Thr(423) --> m5His(478)). All experimental data are consistent with the notion that the two altered threonine residues face each other at the TM I/TM VII interface in the pharmacologically inactive m2/m5 hybrid receptors, thus interfering with proper helix-helix packing. Our data provide the first experimental evidence as to how TM I and TM VII are oriented relative to each other and also strongly suggest that the TM helices in G protein-coupled receptors are arranged in a counterclockwise fashion (as viewed from the extracellular membrane surface). C1 NIDDK, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. NR 39 TC 65 Z9 65 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 1995 VL 270 IS 33 BP 19532 EP 19539 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300053 PM 7642637 ER PT J AU MILOSO, M MAZZOTTI, M VASS, WC BEGUINOT, L AF MILOSO, M MAZZOTTI, M VASS, WC BEGUINOT, L TI SHC AND GRB-2 ARE CONSTITUTIVELY ACTIVATED BY AN EPIDERMAL GROWTH-FACTOR RECEPTOR WITH A POINT MUTATION IN THE TRANSMEMBRANE DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; EGF RECEPTOR; AUTOPHOSPHORYLATION SITES; SIGNAL TRANSDUCTION; ONCOGENIC FORMS; PHOSPHORYLATION; TRANSFORMATION; SUBSTITUTION; GENE AB A single point mutation, Glu(627) --> Val, equivalent to the activating mutation in the Neu oncogene, was inserted in the transmembrane domain of the human epidermal growth factor (EGF) receptor. Unlike the wild type, Glu(627)-EGF receptor, transfected in NIH3T3 cells, gave rise to focal transformation and growth in agar even in the absence of EGF. Constitutive activity of mutant EGF receptor amounted to 20% of that of wild type receptor stimulated by EGF. In addition, the mutant receptor was more sensitive to EGF, reaching maximum transforming activity at 5 ng/ml EGF, NIH3T3 cells expressing Glu(627)-EGF receptor showed a transformed phenotype and were not arrested in G(0) upon serum deprivation, The mutant receptor was constitutively autophosphorylated. and several other cellular proteins were phosphorylated on tyrosine in absence of the ligand. Among these, the SHC adaptor protein was phosphorylated in absence of EGF, the other adaptor, GRB-2, was constitutively associated with the Glu(627)-EGF receptor in vivo and in vitro, and mitogen-activated protein kinase was constitutively phosphorylated. In contrast, other EGF receptor substrates, like phospholipase C gamma, were not phosphorylated in absence of EGF. The mutant receptor showed a higher sensitivity to cleavage by calpain both in absence and presence of EGF, appeared as a 170- and 150-kDa doublet in cell extracts, and a specific calpain inhibitor blocked the appearance of the 150-kDa form. Since the calpain cleavage site is located in the receptor cytoplasmic tail, this finding suggests that the Glu(627) mutation induces a slightly different conformation in the EGF receptor intracellular domain. In conclusion, our data show that a point mutation in the EGF receptor transmembrane domain was able to constitutively activate the receptor and to induce transformation via constitutive activation of the Ras pathway. C1 HOSP SAN RAFFAELE,DIBIT,MOLEC ONCOL LAB,I-20132 MILAN,ITALY. HOSP SAN RAFFAELE,CNR,IST NEUROSCI & BIOIMMAGINI,I-20132 MILAN,ITALY. NIH,MOLEC ONCOL LAB,BETHESDA,MD 20892. NR 41 TC 39 Z9 40 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 AUG 18 PY 1995 VL 270 IS 33 BP 19557 EP 19562 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300057 PM 7642641 ER PT J AU LEHEL, C OLAH, Z JAKAB, G SZALLASI, Z PETROVICS, G HARTA, G BLUMBERG, PM ANDERSON, WB AF LEHEL, C OLAH, Z JAKAB, G SZALLASI, Z PETROVICS, G HARTA, G BLUMBERG, PM ANDERSON, WB TI PROTEIN-KINASE-C-EPSILON SUBCELLULAR-LOCALIZATION DOMAINS AND PROTEOLYTIC DEGRADATION SITES - A MODEL FOR PROTEIN-KINASE-C CONFORMATIONAL-CHANGES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHORBOL ESTER; SIGNAL TRANSDUCTION; REGULATORY DOMAIN; PKC-EPSILON; CELLS; ASSOCIATION; ACTIVATION; ISOFORM; FIBROBLASTS; MORPHOLOGY AB Protein kinase C (PKC) epsilon has been found to have unique properties among the PKC isozymes in terms of its membrane association, oncogenic potential, and substrate specificity, Recently we have demonstrated that PKC epsilon localizes to the Golgi network via its zinc finger domain and that both the holoenzyme and its zinc finger region modulate Golgi function. To further characterize the relationship between the domain organization and the subcellular localization of PKC epsilon, a series of NIH 3T3 cell lines were created, each overexpressing a different truncated version of PKC epsilon. The overexpressed proteins each were designed to contain an epsilon-epitope tag peptide at the COOH terminus to allow ready detection with an antibody specific for the tag. The subcellular localization of the recombinant proteins was analyzed by in vivo phorbol ester binding, immunocytochemistry, and cell fractionation followed by immunoblotting. Results revealed several regions of PKC epsilon that contain putative subcellular localization signals. The presence either of the hinge region or of a 33-amino-acid region including the pseudosubstrate sequence in the recombinant proteins resulted in association with the plasma membrane and cytoskeletal components. The catalytic domain was found predominantly in the cytosolic fraction. The accessibility and thus the dominance of these localization signals is likely to be affected by the overall conformation of the recombinant proteins. Regions with putative proteolytic degradation sites also were identified. The susceptibility of the overexpressed proteins to proteolytic degradation was dependent on the protein conformation. Based on these observations, a model depicting the interaction and hierarchy of the suspected localization signals and proteolytic degradation sites is presented. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 38 TC 62 Z9 62 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 AUG 18 PY 1995 VL 270 IS 33 BP 19651 EP 19658 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP703 UT WOS:A1995RP70300070 PM 7642654 ER PT J AU TAUB, DD KEY, ML CLARK, D TURCOVSKICORRALES, SM AF TAUB, DD KEY, ML CLARK, D TURCOVSKICORRALES, SM TI CHEMOTAXIS OF T-LYMPHOCYTES ON EXTRACELLULAR-MATRIX PROTEINS ANALYSIS OF THE IN-VITRO METHOD TO QUANTITATE CHEMOTAXIS OF HUMAN T-CELLS SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CHEMOKINE; CHEMOTAXIS; T CELL; EXTRACELLULAR MATRIX ID ENDOTHELIAL-CELLS; CYTOKINE FAMILY; INTERLEUKIN-2; MIP-1-ALPHA; LEUKOCYTES; MIP-1-BETA; MONOCYTES; MIGRATION; C5A AB The present report compares a variety of T cell purification protocols and chemotaxis procedures in assessing chemokine-induced T cell migration using a microchemotaxis assay. Rapidly purified T cells are capable of directly responding to the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES in the absence of alpha CD3 stimulation as previously described (Taub, D.D. and Oppenheim, J.J. (1993) Cytokine 5, 175). However, T cell purification schemes involving prolonged 37 degrees C incubations generally produce non-motile T lymphocytes that require stimulation with alpha CD3 antibody for 6-12 h in culture to recover chemotactic mobility. This loss of chemotactic potential appears to be due to prolonged 37 degrees C incubations as rapidly purified T cells lose migratory activity upon incubation at 37 degrees C. Radiolabeled binding analysis revealed that beta chemokine binding sites are downregulated as short as 2 h after incubation at 37 degrees C. T cells require the presence of extracellular matrix molecules to facilitate T cell migration. While many of these proteins permit chemotactic activity, human plasma and foreskin fibronectin were found to be the most effective matrix molecule for T cell migration. Kinetic analysis of T cell activation revealed that 6-12 h of anti-CD3 stimulation was optimal to restore the ability of purified T cells to migrate in response to the chemokines MIP-1 alpha, MIP-1 beta, RANTES, and IL-8. However, rapidly dividing T cells (greater than or equal to 48 h post alpha CD3 mAb stimulation) fail to migrate in response to any chemotactic stimulus. Together, these results suggest that the measurement of T cell migration, using microchemotaxis chambers, is a multifactorial process with strict environmental and activation requirements. RP TAUB, DD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP INC,CLIN SUPPORT LAB,BLDG 560,ROOM 11-23,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 27 TC 38 Z9 38 U1 0 U2 0 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 AUG 18 PY 1995 VL 184 IS 2 BP 187 EP 198 DI 10.1016/0022-1759(95)00087-Q PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA RR941 UT WOS:A1995RR94100006 PM 7544817 ER PT J AU VOWELLS, SJ FLEISHER, TA AF VOWELLS, SJ FLEISHER, TA TI REACTION TO VOWELLS ET-AL - REPLY SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Letter C1 NIH,WARREN G MAGNUSON CLIN CTR,SERV IMMUNOL,BETHESDA,MD 20892. NIAID,HOST DEF LAB,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 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 18 PY 1995 VL 184 IS 2 BP 279 EP 279 DI 10.1016/0022-1759(95)90020-9 PG 1 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA RR941 UT WOS:A1995RR94100016 ER PT J AU HEJCHMAN, E HAUGWITZ, RD CUSHMAN, M AF HEJCHMAN, E HAUGWITZ, RD CUSHMAN, M TI SYNTHESIS AND CYTOTOXICITY OF WATER-SOLUBLE AMBROSIN PRODRUG CANDIDATES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID TUMOR-CELL-LINES; SESQUITERPENE AB The potential therapeutic application of the naturally occurring, cytotoxic pseudoguaianolide sesquiterpene lactone ambrosin is limited by its aqueous insolubility. A number of water-soluble ambrosin derivatives have therefore been prepared for potential use as prodrugs. Michael addition of several secondary amines to both the alpha,beta-unsaturated ketone and alpha-methylene lactone moieties of ambrosin afforded tertiary amine diadducts that were converted to water-soluble hydrochloride salts. The salt of the bis-piperidine adduct proved to be the most potent, producing cytotoxic activity only slightly less potent than that of ambrosin itself in a variety of human cancer cell cultures. The sodium salt of the bis-sulfonic acid derivative of ambrosin was inactive, while the sodium salt of the bis-sulfinic acid analog had low activity. Biological evaluation of several ambrosin analogs with reduced and/or isomerized alpha,beta-unsaturated ketone and alpha-methylene lactone moieties demonstrated the importance of both of these functional groups for biological activity. C1 PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ROCKVILLE,MD 20852. FU NCI NIH HHS [N01-CM-17512] NR 26 TC 22 Z9 22 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 18 PY 1995 VL 38 IS 17 BP 3407 EP 3410 DI 10.1021/jm00017a025 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RQ576 UT WOS:A1995RQ57600025 PM 7650694 ER PT J AU HAGEN, SJ HOFRICHTER, J EATON, WA AF HAGEN, SJ HOFRICHTER, J EATON, WA TI PROTEIN REACTION-KINETICS IN A ROOM-TEMPERATURE GLASS SO SCIENCE LA English DT Article ID GEMINATE RECOMBINATION; CONFORMATIONAL-CHANGES; NEUTRON-SCATTERING; HEME-PROTEINS; RELAXATION DYNAMICS; SOLVENT VISCOSITY; LIGAND-BINDING; CO BINDING; MYOGLOBIN; TRANSITION AB Protein reaction kinetics in aqueous solution at room temperature are often simplified by the thermal averaging of conformational substates. These substates exhibit widely varying reaction rates that are usually exposed by trapping in a glass at low temperature. Here, it is shown that the solvent viscosity, rather than the low temperature, is primarily responsible for the trapping. this was demonstrated by placement of myoglobin in a glass at room temperature and subsequent observation of inhomogeneous reaction kinetics. The high solvent viscosity slowed the rate of crossing the energy barriers that separated the substates and also suppressed any change in the average protein conformation after ligand dissociation. RP HAGEN, SJ (reprint author), NIH,PHYS CHEM LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Hagen, Stephen/E-9737-2015 OI Hagen, Stephen/0000-0002-3373-5033 NR 42 TC 185 Z9 185 U1 0 U2 7 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 18 PY 1995 VL 269 IS 5226 BP 959 EP 962 DI 10.1126/science.7638618 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP738 UT WOS:A1995RP73800030 PM 7638618 ER PT J AU DESIMONE, R AF DESIMONE, R TI NEUROPSYCHOLOGY - IS DOPAMINE A MISSING LINK SO NATURE LA English DT Editorial Material ID DELAYED ALTERNATION; UNIT-ACTIVITY RP DESIMONE, R (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 12 TC 26 Z9 26 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 17 PY 1995 VL 376 IS 6541 BP 549 EP 550 DI 10.1038/376549a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP756 UT WOS:A1995RP75600023 PM 7637797 ER PT J AU RYU, S AF RYU, S TI GENE-EXPRESSION AND MESSENGER-RNA SO NATURE LA English DT Letter ID ESCHERICHIA-COLI; MESSENGER-RNA; AMS RP RYU, S (reprint author), NCI,MOLEC BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 8 TC 5 Z9 5 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 17 PY 1995 VL 376 IS 6541 BP 560 EP 560 DI 10.1038/376560a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP756 UT WOS:A1995RP75600037 PM 7637802 ER PT J AU WYNN, TA CHEEVER, AW JANKOVIC, D POINDEXTER, RW CASPAR, P LEWIS, FA SHER, A AF WYNN, TA CHEEVER, AW JANKOVIC, D POINDEXTER, RW CASPAR, P LEWIS, FA SHER, A TI AN IL-12-BASED VACCINATION METHOD FOR PREVENTING FIBROSIS INDUCED BY SCHISTOSOME INFECTION SO NATURE LA English DT Article ID TUMOR NECROSIS FACTOR; MURINE SCHISTOSOMIASIS; IMMUNE-RESPONSE; MESSENGER-RNA; MANSONI; MICE; INFLAMMATION; INDUCTION; INVIVO; BETA AB THE harmful fibrosis which often occurs in the context of infectious. disease involves the excessive deposition of connective tissue matrix, particularly collagen, and is mostly resistant to pharmacological and immunological intervention(1). In schistosomiasis, fibrosis is associated with the granulomatous response to parasite eggs trapped in the liver(2). We have previously shown that interleukin (IL)-12 administered peritoneally with eggs prevents subsequent pulmonary granuloma formation on intravenous challenge with eggs(3). Here we show that sensitization with eggs plus IL-12 partly inhibits granuloma formation and dramatically reduces the tissue fibrosis induced by natural infection with Schistosoma mansoni worms. These results are an example of a vaccine against parasites which acts by preventing pathology rather than infection. IL-12, is known to favour the priming of Th1 rather than Th2 cells, and the effects on fibrosis are accompanied by replacement of the Th2-dominated pattern of cytokine expression characteristic of S. mansoni infection with one dominated by Th1 cytokines. Elevated Th2 cytokine expression and fibrosis are common manifestations of a wide variety of infectious diseases and atopic disorders which might be ameliorated by vaccination with antigen and IL-12. C1 NIAID,PARASIT DIS LAB,HOST PARASITE SECT,BETHESDA,MD 20892. BIOMED RES INST,ROCKVILLE,MD 20852. RP WYNN, TA (reprint author), NIAID,PARASITOL LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 27 TC 327 Z9 339 U1 0 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 17 PY 1995 VL 376 IS 6541 BP 594 EP 596 DI 10.1038/376594a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP756 UT WOS:A1995RP75600051 PM 7637808 ER PT J AU MYERS, RL CHEDID, M TRONICK, SR CHIU, IM AF MYERS, RL CHEDID, M TRONICK, SR CHIU, IM TI DIFFERENT FIBROBLAST-GROWTH-FACTOR-1 (FGF-1) TRANSCRIPTS IN NEURAL TISSUES, GLIOBLASTOMAS AND KIDNEY CARCINOMA CELL-LINES SO ONCOGENE LA English DT Note DE AFGF; ALTERNATIVE SPLICING; GLIOBLASTOMA; RETINA; DIABETIC RETINOPATHY; ALTERNATIVE PROMOTER USAGE ID FACTOR MESSENGER-RNA; SMOOTH-MUSCLE CELLS; FACTOR-I; EPITHELIAL-CELLS; GENE-EXPRESSION; HUMAN GLIOMA; ACIDIC FGF; CLONING; FAMILY; SEQUENCE AB We have previously reported the tissue specific distribution of four different FGF-1 transcripts containing alternative 5' untranslated exons Spliced to the first protein coding exon. The predominant transcript in brain is FGF-1.B and in kidney FGF-1.A. Others have shown, by in situ hybridization and immunohistochemical analysis, that expression of FGF-1 in the brain is exclusively in neural cells but not in glial cells. Here we have examined the distribution of FGF-1.B and FGF-1.A transcripts in glioblastoma and retinal tissues and in kidney carcinoma cell lines. Our results show that FGF-1.B is the predominant transcript in neural derived tissues including both the diabetic retina and normal retina tissues. Surprisingly, FGF-1.B transcript is highly expressed in glioblastoma tissues. In contrast, a normal brain glial cell line, CHII, expresses very low levels of FGF-1 mRNA. These results strongly implicate the role of FGF-1 in the etiology of glioblastoma. We also examined several kidney carcinoma derived cell lines for the expression of FGF-1 mRNA. Most of these kidney cell lines do not express any FGF-1 transcripts. An interpretation by deduction is that kidney adenocarcinomas are derived from cortex but medulla has been reported as the site of FGF-I synthesis. Of the kidney derived cell lines which are positive for FGF-1 message, only one expressed FGF-1.A transcript. The data may suggest that the establishment of kidney cell lines results in a switch of promoter usage from the 1.A seen in kidney tissue. Similarly, culturing of glioma cell lines may result in a snitch from FGF-1.B seen in glioma tissues to FGF-1.D seen in most glioma cell lines. Continued studies of the FGF-1 transcripts, their functional promoters and their tissues distribution will provide insight into the potential role of FGF-1 in cell growth, tissue differentiation and malignant transformation. C1 OHIO STATE UNIV,DEPT INTERNAL MED,COLUMBUS,OH 43210. OHIO STATE UNIV,CTR COMPREHENS CANC,COLUMBUS,OH 43210. NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. SANTA CRUZ BIOTECHNOL INC,SANTA CRUZ,CA 95060. RI Chiu, Ing-Ming/B-1534-2008 FU NCI NIH HHS [T32 CA09338, R01 CA45611]; NINDS NIH HHS [P20 NS31087] NR 40 TC 27 Z9 27 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 17 PY 1995 VL 11 IS 4 BP 785 EP 789 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RQ469 UT WOS:A1995RQ46900022 PM 7544453 ER PT J AU CUNNINGHAM, ML SOLIMAN, MS BADR, MZ MATTHEWS, HB AF CUNNINGHAM, ML SOLIMAN, MS BADR, MZ MATTHEWS, HB TI ROTENONE, AN ANTICARCINOGEN, INHIBITS CELLULAR PROLIFERATION BUT NOT PEROXISOME PROLIFERATION IN MOUSE-LIVER SO CANCER LETTERS LA English DT Article DE ROTENONE; WY-14,643; HEPATOCELLULAR PROLIFERATION; PEROXISOME PROLIFERATION; BETA-OXIDATION; HEPATOCARCINOGENESIS ID HEPATOCELLULAR PROLIFERATION; DNA-SYNTHESIS; HEPATOCARCINOGENICITY; RATS AB In previous National Toxicology Program (NTP) studies, rotenone reduced the background incidence of hepatocellular carcinoma in male B6C3F1 mice. In the present studies, rotenone reduced the basal hepatic labeling index of male B6C3F1 mice in a dose-dependent fashion and inhibited hepatocellular proliferation, but not peroxisome proliferation, induced by the peroxisome proliferator Wy-14,643. These results indicate that reduction of hepatic tumors by rotenone may have been due to decreased liver cell replication, that peroxisome proliferation can be induced in the absence of hepatocellular proliferation and suggest rotenone as a potential tool in studies of relationships of cell proliferation, peroxisomal proliferation and hepato-carcinogenesis. C1 UNIV MISSOURI,DIV PHARMACOL,KANSAS CITY,MO 64110. RP CUNNINGHAM, ML (reprint author), NIEHS,CHEM BRANCH,MAIL DROP B3-10,RES TRIANGLE PK,NC 27709, USA. OI soliman, Mahmoud/0000-0003-1948-7464 NR 19 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 16 PY 1995 VL 95 IS 1-2 BP 93 EP 97 DI 10.1016/0304-3835(95)03869-X PG 5 WC Oncology SC Oncology GA RR830 UT WOS:A1995RR83000014 PM 7656250 ER PT J AU CHEN, LC TARONE, R HUYNH, M DE LUCA, LM AF CHEN, LC TARONE, R HUYNH, M DE LUCA, LM TI HIGH DIETARY RETINOIC ACID INHIBITS TUMOR PROMOTION AND MALIGNANT CONVERSION IN A 2-STAGE SKIN CARCINOGENESIS PROTOCOL USING 7,12-DIMETHYLBENZ[ALPHA]ANTHRACENE AS THE INITIATOR AND MEZEREIN AS THE TUMOR PROMOTER IN FEMALE SENCAR MICE SO CANCER LETTERS LA English DT Article DE MALIGNANT CONVERSION; MEZEREIN; RETINOIC ACID; SKIN CARCINOGENESIS; 12-O-TETRADECANOYLPHORBOL-13-ACETATE; TUMOR PROMOTION AB We studied the effect of dietary retinoic acid (RA) in a two-stage protocol of skin carcinogenesis in female SENCAR mice, At 3 weeks of age mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA, 20 mu g) and promoted with either 12-O-tetradecanoylphsrbol-13-acetate (TPA, 2 mu g) once per week or mezerein (MEZ, 4 mu g) twice per week for 20 weeks, At the week of DMBA initiation mice were also put on a purified diet containing either 3 (physiological dose) or 30 mu g (pharmacological dose) of RA/g of diet. High dietary RA significantly inhibited papilloma yield but not incidence in the MEZ-promoted group. Papilloma incidence and yield were also lower in the MEZ- than in the TPA-treated groups. Cumulative carcinoma incidence and yield, and conversion efficiency (= (carcinomas/maximal papillomas) x 100%), were all decreased by high dietary RA in both MEZ- and TPA-treated groups. These results demonstrate that high dietary RA inhibited skin carcinogenesis in MEZ-promoted mice at the stages of tumor promotion and malignant conversion, while this inhibition occurred only at the malignant conversion stage in TPA-promoted mice. C1 NCI, BETHESDA, MD 20892 USA. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT, BETHESDA, MD 20892 USA. NR 16 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 16 PY 1995 VL 95 IS 1-2 BP 113 EP 118 DI 10.1016/0304-3835(95)03868-W PG 6 WC Oncology SC Oncology GA RR830 UT WOS:A1995RR83000017 PM 7656218 ER PT J AU TORI, TT ELWELL, MR MORRIS, RW MARONPOT, RR AF TORI, TT ELWELL, MR MORRIS, RW MARONPOT, RR TI DEVELOPMENT AND PERSISTENCE OF PLACENTAL GLUTATHIONE-S-TRANSFERASE POSITIVE FOCI IN LIVERS OF MALE F344 RATS EXPOSED TO O-NITROTOLUENE SO CANCER LETTERS LA English DT Article DE O-NITROTOLUENE; PLACENTAL GLUTATHIONE S-TRANSFERASE-POSITIVE FOCI; RAT HEPATOCARCINOGENESIS; STEREOLOG ID MACROMOLECULAR COVALENT BINDING; ALTERED HEPATIC FOCI; CHEMICAL HEPATOCARCINOGENESIS; HISTOCHEMICAL MARKERS; PRENEOPLASTIC CELLS; FISCHER-344 RATS; MONONITROTOLUENES; DINITROTOLUENE; GENOTOXICITY; WITHDRAWAL AB In a previous 13-week study of o-nitrotoluene, a chemical-related increase in liver weight, hepatocellular vacuolization, and oval cell hyperplasia in male F344 rats was reported. In this study, the occurrence and change in number and size of hepatic foci in male F344 rats fed a diet containing 5000 ppm o-nitrotoluene or a control diet for 13 weeks, 26 weeks, and 13 weeks followed by a 13-week recovery period (26-week stop-exposure) were evaluated. The livers were stained immunohistochemically for placental glutathione S-transferase (PGST), a marker of hepatic preneoplasia, and quantified stereologically using computer-assisted image analysis. Exposure to o-nitrotoluene induced PGST-positive (PGST+) liver foci in all treatment groups. The 26-week continuous-exposure group produced more PGST+ liver foci (961.4 foci/cm(3) versus 445.4 foci/cm(3)) and greater mean focus volume (4.34 mu m(3) versus 1.34 mu m(3)) than the 13-week continuous-exposure group. In the 26-week stop-exposure group, there were fewer PGST+ liver foci (181.4 foci/cm(3)) than observed with continuous exposure at 13 weeks or 26 weeks; however, the mean focal volume in the stop-exposure group at 26 weeks (5.33 mu m(3)) was greater than that at 13 weeks (1.34 mu m(3)) or 26 weeks of continuous exposure (4.34 mu m(3)). These findings demonstrate that (1) PGST+ foci are observed after only 13 weeks of exposure to o-nitrotoluene; (2) the number and size of foci increase with continued exposure for 26 weeks; and (3) although the number of PGST+ foci decreases with time after chemical exposure is discontinued, many PGST+ foci do not regress but increase in size during the recovery period of 13 weeks. The persistence and increase in size of these foci, even in the absence of chemical exposure, suggest the potential for a hepatocarcinogenic effect in long-term studies for o-nitrotoluene. C1 ANALYT SCI INC,DURHAM,NC 27711. RP TORI, TT (reprint author), NIEHS,EXPTL PATHOL LAB,111 TW ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 16 PY 1995 VL 95 IS 1-2 BP 167 EP 173 PG 7 WC Oncology SC Oncology GA RR830 UT WOS:A1995RR83000025 ER PT J AU CALVERT, RJ TASHIRO, Y BUZARD, GS DIWAN, BA WEGHORST, CM AF CALVERT, RJ TASHIRO, Y BUZARD, GS DIWAN, BA WEGHORST, CM TI LACK OF P53 POINT MUTATIONS IN CHEMICALLY-INDUCED MOUSE HEPATOBLASTOMAS - AN END-STAGE, HIGHLY MALIGNANT HEPATOCELLULAR TUMOR SO CANCER LETTERS LA English DT Article DE MICE; P53; LIVER; TUMOR; HEPATOBLASTOMA; SINGLE-STRAND CONFORMATION POLYMORPHISM; N,N-NITROSODIETHYIAMINE; PHENOBARBITAL ID LIVER-TUMORS; N-NITROSODIETHYLAMINE; LUNG-TUMORS; GENE; CARCINOMAS; EXPRESSION; PSEUDOGENE; OCCUR AB Inactivation of the p53 tumor suppressor gene appears to be an important event in the progression of many types of human neoplasms; however its role in rodent experimental tumorigenesis is controversial. Previous studies have shown that a wide array of chemically induced and spontaneous mouse liver tumors lack p53 mutations within the evolutionarily conserved regions of exons 5-8. However, since p53 inactivation in human neoplasms occurs relatively late in tumor progression, it is possible that the mouse liver tumors evaluated previously were not suitably advanced to incur p53 aberrations. In the present study, we examined an end-stage, highly malignant embryonal mouse liver tumor known as the hepatoblastoma (HB) for p53 mutations utilizing the highly sensitive 'cold' single-strand conformation polymorphism (SSCP) technique. In addition, several of the HBs were examined by direct nucleotide sequencing. No aberrations of the p53 gene were detected within exons 5-8 of any of the 16 HBs examined. These results confirm that the p53 gene plays a minimal role in the development or malignant progression of hepatocellular tumors in mice. C1 US FDA,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,LAUREL,MD. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS DEV PROGRAM,SAIC FREDERICK,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD. NR 31 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 16 PY 1995 VL 95 IS 1-2 BP 175 EP 180 DI 10.1016/0304-3835(95)03884-Y PG 6 WC Oncology SC Oncology GA RR830 UT WOS:A1995RR83000026 PM 7656227 ER PT J AU ZHU, ZW PETERING, DH SHAW, CF AF ZHU, ZW PETERING, DH SHAW, CF TI ELECTROSTATIC INFLUENCES ON THE KINETICS OF THE REACTIONS OF LOBSTER METALLOTHIONEINS WITH THE ELECTROPHILIC DISULFIDES 2,2'-DITHIODIPYRIDINE (PYSSPY) AND 5,5'-DITHIOBIS(2-NITROBENZOIC ACID) (ESSE) SO INORGANIC CHEMISTRY LA English DT Article ID RABBIT LIVER METALLOTHIONEIN; COPPER-METALLOTHIONEINS; HOMARUS-AMERICANUS; SCYLLA-SERRATA; CLUSTERS; BINDING; DOMAIN; THIOLS; DTNB; SITE AB Metallothioneins (MT) are ubiquitous proteins which can interact with electrophiles including alkylating agents and gold- and platinum-dependent chemotherapeutic agents and reactive oxygen species. Crustacean MTs are useful model systems due to modifications of stoichiometry and structure. Electrostatic influences on the reactions of lobster hepatopancreas MT-1 and MT-2 with two electrophilic disulfides were investigated. 5,5'-Dithiobis-(2-nitrobenzoic acid), ESSE, and 2,2'-dithiodipyridine, PySSPy, react biphasically. Each phase has disulfide dependent and independent terms, yielding a four-term rate law: rate = k(1s)[MT] + k(2s)[RSSR][MT] + k(1f)[MT] + k(2f)[RSSR][MT]. The neutral disulfide PySSPy reacts more rapidly and has significantly greater second order rate constants than the negatively (-2) charged DTNB. The MT-1 rate constants in 5 mM Tris-HCl-100 mM KCl buffer, pH 7.4, at 25 degrees C are k(2f) = 52.5 and k(2s) = 3.65 M(-1) s(-1) for PySSPy and k(2f) = 5.80 and k(2s) = 0.70 M(-1) s(-1) for ESSE. Ionic strength studies of the reactions of ESSE and MT-1 showed a positive salt effect with increasing KCl concentration, as expected for a reaction between similarly charged species. The Debye-Huckel law, applied to k(2f) and k(2s), yielded effective charges of -1 for the two protein reaction centers. These values agree with the charges of the two domains (beta(C) and beta(N)) and support a kinetic model in which each phase of the reaction is associated with one of the domains. The reactivities are discussed in light of the novel cadmium-thiolate connectivities of the lobster MT domains. C1 UNIV WISCONSIN,DEPT CHEM,MILWAUKEE,WI 53201. UNIV WISCONSIN,NIEHS,AQUAT & MARINE BIOMED CORE CTR,MILWAUKEE,WI 53201. NR 41 TC 6 Z9 6 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD AUG 16 PY 1995 VL 34 IS 17 BP 4477 EP 4483 DI 10.1021/ic00121a028 PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA RP579 UT WOS:A1995RP57900028 ER PT J AU CUMMINGS, KM SHAH, D AF CUMMINGS, KM SHAH, D TI TRENDS IN SMOKING INITIATION AMONG ADOLESCENTS AND YOUNG-ADULTS - UNITED-STATES, 1980-1989 (REPRINTED FROM MMWR, VOL 44, PG 521-525, 1995) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NCI,BETHESDA,MD 20892. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,OFF SMOKING & HLTH,ATLANTA,GA. RP CUMMINGS, KM (reprint author), ROSWELL PK CANC INST,BUFFALO,NY 14263, USA. NR 11 TC 2 Z9 2 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 AUG 16 PY 1995 VL 274 IS 7 BP 528 EP 529 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RN466 UT WOS:A1995RN46600007 ER PT J AU HAVERKOS, HW DROTMAN, DP AF HAVERKOS, HW DROTMAN, DP TI THE SOCIAL-ORGANIZATION OF SEXUALITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA. RP HAVERKOS, HW (reprint author), NIH,ROCKVILLE,MD 20857, USA. NR 6 TC 0 Z9 0 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 AUG 16 PY 1995 VL 274 IS 7 BP 535 EP 536 DI 10.1001/jama.274.7.535 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RN466 UT WOS:A1995RN46600016 PM 7629977 ER PT J AU CORTI, MC GURALNIK, JM SALIVE, ME HARRIS, T FIELD, TS WALLACE, RB BERKMAN, LF SEEMAN, TE GLYNN, RJ HENNEKENS, CH HAVLIK, RJ AF CORTI, MC GURALNIK, JM SALIVE, ME HARRIS, T FIELD, TS WALLACE, RB BERKMAN, LF SEEMAN, TE GLYNN, RJ HENNEKENS, CH HAVLIK, RJ TI HDL CHOLESTEROL PREDICTS CORONARY HEART-DISEASE MORTALITY IN OLDER PERSONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIGH-DENSITY LIPOPROTEIN; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; CARDIOVASCULAR-DISEASE; SERUM-CHOLESTEROL; RISK-FACTORS; FOLLOW-UP; FRAMINGHAM; PREVALENCE; HEALTH AB Objectives.-To examine the relationship of total cholesterol and high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) mortality and with occurrence of new CHD events in persons aged 71 years and older. Design.-Prospective cohort study with a median of 4.4 years of follow-up. Setting.-East Boston, Mass; New Haven, Conn; and Iowa and Washington counties, Iowa. Participants.-A total of 2527 women and 1377 men who completed an interview, had serum lipid determinations, and survived at least 1 year. New CHD events were evaluated in persons with no CHD history or hospitalization. Main Outcome Measures.-Death due to CHD (ICD-9 codes 410 through 414 as underlying cause of death); new occurrence of CHD events (fatal CHD or hospitalization with CHD [ICD-9 codes 410 through 414]). Results.-After adjustment for established CHD risk factors, the relative risk (RR) of death due to CHD for those with low HDL-C (<0.90 mmol/L [<35 mg/dL]) compared with the reference group (HDL-C greater than or equal to 1.55 mmol/L [greater than or equal to 60 mg/dL]) was 2.5 (95% confidence interval [Cl], 1.6 to 4.0). Elevated risk was present in subgroups aged 71 through 80 years (RR, 4.1; 95% Cl, 1.9 to 8.8) and over 80 years (RR, 1.8; 95% Cl, 0.99 to 3.4), and in men and women. Low HDL-C predicted an increased risk of occurrence of new CHD events (RR, 1.4, 95% Cl, 1.1 to 2.0), with similar but nonsignificant results in subgroups of men and women. Total cholesterol was less consistently associated with CHD mortality than HDL-C. When we compared individuals with total cholesterol of at least 6.20 mmol/L (240 mg/dL) with the reference group with total cholesterol of 4.16 to 5.19 mmol/L (161 to 199 mg/dL), a significant risk of CHD mortality was seen for women (RR, 1.8; 95% Cl, 1.03 to 3.0) but not for men (RR, 1.0; 95% Cl, 0.5 to 2.0). In the total population, for each 1-unit increase in the total cholesterol/HDL-C ratio there was a 17% increase in the risk of CHD death that was statistically significant. Conclusions.-Low HDL-C predicts CHD mortality and occurrence of new CHD events in persons older than 70 years. Elevated total cholesterol was not found to be associated with CHD mortality in older men, but may be a risk factor for CHD in older women. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV PREVENT MED,BOSTON,MA 02115. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP CORTI, MC (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,ROOM 3C309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 42 TC 186 Z9 188 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 16 PY 1995 VL 274 IS 7 BP 539 EP 544 DI 10.1001/jama.274.7.539 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RN466 UT WOS:A1995RN46600023 PM 7629981 ER PT J AU HENRARD, DR PHILLIPS, JF MUENZ, LR BLATTNER, WA WIESNER, D EYSTER, ME GOEDERT, JJ AF HENRARD, DR PHILLIPS, JF MUENZ, LR BLATTNER, WA WIESNER, D EYSTER, ME GOEDERT, JJ TI NATURAL-HISTORY OF HIV-1 CELL-FREE VIREMIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; HOMOSEXUAL MEN; VIRAL BURDEN; INFECTION; AIDS; PLASMA; TYPE-1; BLOOD AB Objective.-To characterize the natural history of viremia with human immunodeficiency virus type 1 (HIV-1) and its association with disease progression from infection to acquired immunodeficiency syndrome (AIDS). Design.-Prospective cohort study. Annual specimens were tested for quantitative virion-associated HIV-1 RNA, p24 antigen, and CD4(+) lymphocyte levels. Participants.-A total of 42 homosexual men who seroconverted to HIV-1 between 1982 and 1985. Main Outcome Measures.-Trends over time in serum HIV-1 RNA level, correlations between serum HIV-1 RNA and other markers, and prediction of AIDS using these markers. ResuIts.-HIV-1 RNA levels were stable overtime, increasing by 10-fold or more in only six (14%) of the 42 subjects during 3 to 11 years of follow-up. Mean HIV-1 RNA levels were 10(3.8) copies/mL if AIDS occurred in less than 4 years, 10(3.07) copies/mL if AIDS developed within 4 through 9 years, and 10(2.27) copies/mL if AIDS did not develop within 6 through 11 years. In both univariate and multivariate models, initial and subsequent HIV-1 RNA levels, p24 antigenemia, and percentage of CD4(+) lymphocytes were independently predictive of AIDS. Conclusions.-The stability of virion-associated HIV-1 RNA levels suggests that an equilibrium between HIV-1 replication rate and efficacy of immunologic response is established shortly after infection and persists throughout the asymptomatic period of the disease. Thus, defective immunologic control of HIV-1 infection may be as important as the viral replication rate for determining AIDS-free survival. Because individual steady-state levels of viremia were established soon after infection, HIV-1 RNA levels may be useful markers for predicting clinical outcome. C1 ABBOTT LABS,DEPT MED RES,N CHICAGO,IL 60064. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT MED,DIV HEMATOL,HERSHEY,PA 17033. FU NCI NIH HHS [N01-CP-33060, N01-CP-40521, N01-CP-95612] NR 34 TC 165 Z9 167 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 16 PY 1995 VL 274 IS 7 BP 554 EP 558 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RN466 UT WOS:A1995RN46600026 PM 7629984 ER PT J AU SHIRANI, J BEREZOWSKI, K ROBERTS, WC AF SHIRANI, J BEREZOWSKI, K ROBERTS, WC TI QUANTITATIVE MEASUREMENT OF NORMAL AND EXCESSIVE (COR ADIPOSUM) SUBEPICARDIAL ADIPOSE-TISSUE, ITS CLINICAL-SIGNIFICANCE, AND ITS EFFECT ON ELECTROCARDIOGRAPHIC QRS VOLTAGE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID NECROPSY; HEART AB The hearts of most adults in the Western world contain varying amounts of fat, mainly in the subepicardial tissue. Although little attention is now given to these fatty deposits, about 100 years ago the fatty heart was considered to be the most common cause of sudden cardiac death.(1) The contribution of cardiac adipose tissue to cardiac weight has received no attention. This report describes the percentage of the cardiac mass consisting of adipose tissue and the total 12-lead QRS voltage in 30 adults without clinical evidence of cardiac disease, and summarizes real and potential clinical consequences of excessive subepicardial adipose tissue. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 11 TC 95 Z9 98 U1 0 U2 2 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 1995 VL 76 IS 5 BP 414 EP 418 DI 10.1016/S0002-9149(99)80116-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RN759 UT WOS:A1995RN75900024 PM 7639175 ER PT J AU DOPPMAN, JL CHANG, R FRAKER, DL NORTON, JA ALEXANDER, HR MILLER, DL COLLIER, E SKARULIS, MC GORDEN, P AF DOPPMAN, JL CHANG, R FRAKER, DL NORTON, JA ALEXANDER, HR MILLER, DL COLLIER, E SKARULIS, MC GORDEN, P TI LOCALIZATION OF INSULINOMAS TO REGIONS OF THE PANCREAS BY INTRAARTERIAL STIMULATION WITH CALCIUM SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE INSULINOMA; CALCIUM; HEPATIC VEINS; ANGIOGRAPHY; PANCREAS ID SELECTIVE INTRAARTERIAL INJECTION; ZOLLINGER-ELLISON SYNDROME; INTRAOPERATIVE ULTRASONOGRAPHY; INFUSION; GASTRINOMAS; SECRETION; RELEASE AB Objective: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. Design and Patients: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. Setting: Tertiary referral hospital. Measurements: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9) Results: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. Conclusion: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas. C1 NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. WASHINGTON UNIV, ST LOUIS, MO USA. RP DOPPMAN, JL (reprint author), NIH, CTR CLIN,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C660, 10 CTR DR, MSC 1182, BETHESDA, MD 20892 USA. NR 20 TC 180 Z9 189 U1 0 U2 1 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 AUG 15 PY 1995 VL 123 IS 4 BP 269 EP 273 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RN665 UT WOS:A1995RN66500004 PM 7611592 ER PT J AU SHELHAMER, JH LEVINE, SJ WU, T JACOBY, DB KALINER, MA RENNARD, SI AF SHELHAMER, JH LEVINE, SJ WU, T JACOBY, DB KALINER, MA RENNARD, SI TI AIRWAY INFLAMMATION SO ANNALS OF INTERNAL MEDICINE LA English DT Discussion ID BRONCHIAL EPITHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; PULMONARY PARASYMPATHETIC NERVES; INTERLEUKIN-8 GENE-EXPRESSION; TACHYKININ-INDUCED INCREASE; COLONY-STIMULATING FACTOR; M2 MUSCARINIC RECEPTORS; CHALLENGED GUINEA-PIGS; CILIARY BEAT FREQUENCY; NEUTRAL ENDOPEPTIDASE AB Diseases characterized by airway inflammation, excessive airway secretion, and airway obstruction affect a substantial proportion of the population. These diseases include asthma, chronic bronchitis, bronchiectasis, and cystic fibrosis. Asthma and chronic bronchitis may affect 25 million persons in the United States. Much progress has been made in the last decade toward an understanding of the mechanisms underlying chronic airway inflammation; recent work has resulted in several new concepts of the initiation and maintenance of airway inflammation. Airway production of chemokines, cytokines, and growth factors in response to irritants, infectious agents, and inflammatory mediators may play an important role in the modulation of acute and chronic airway inflammation. Lipid mediators may be produced by resident airway cells and by inflammatory cells; production of these mediators may also be altered by inflammatory cytokines. Increased airway obstruction may be related to intercurrent viral respiratory infection and to the induction of airway inflammation and airway hyperreactivity that results from such infection. Furthermore, several models exist to explain the processes by which airway inflammation is perpetuated in diseases such as asthma and chronic bronchitis. These include neurogenic inflammation, the perpetuation of the acute inflammatory response, and cycles of airway epithelial cell-mediated and inflammatory cell-mediated recruitment and activation of inflammatory cells. An understanding of these mechanisms of airway inflammation may provide the clinician with new therapeutic approaches to the treatment of these common and chronic diseases. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. INST ASTHMA & ALLERGY,WASHINGTON,DC 20010. UNIV NEBRASKA,SCH MED,DEPT MED,OMAHA,NE 68198. RP SHELHAMER, JH (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7-D-43,BETHESDA,MD 20892, USA. NR 162 TC 92 Z9 93 U1 0 U2 2 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 AUG 15 PY 1995 VL 123 IS 4 BP 288 EP 304 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA RN665 UT WOS:A1995RN66500008 PM 7611596 ER PT J AU UHLINHANSEN, L YANAGISHITA, M AF UHLINHANSEN, L YANAGISHITA, M TI BREFELDIN-A INHIBITS THE ENDOCYTOSIS OF PLASMA-MEMBRANE-ASSOCIATED HEPARAN-SULFATE PROTEOGLYCANS OF CULTURED RAT OVARIAN GRANULOSA-CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID INTRACELLULAR DEGRADATIVE PATHWAYS; COATED PIT FORMATION; TRANS-GOLGI NETWORK; SULFATE PROTEOGLYCANS; CYTOPLASMIC DOMAIN; ORGANELLE STRUCTURE; SECRETORY PROTEINS; MDCK CELLS; A CAUSES; RECEPTOR AB Rat ovarian granulosa cells were labelled with [S-35]sulphate for 0.5-20 h and chased in the presence or absence of 1-2 mu g/ml of brefeldin A (BFA) for up to 21 h. Heparan [S-35]sulphate (HS) proteoglycans from the culture medium, plasma membrane and intracellular fractions were then analysed by gel chromatography. In the absence of BFA, about 85% of the plasma membrane-associated HS proteoglycans were endocytosed and subsequently degraded intracellularly. Recirculation of the HS proteoglycans between the intracellular pool and the cell surface was not observed. Exposing the cells to BFA for less than Ih did not influence the turnover of the HS proteoglycans, whereas the effect of the drug on the Golgi functions reached a maximum in approx. 10 min. When the cells were treated with BFA for more than 1-2 h, the rate of endocytosis of HS proteoglycans was reduced to about 50% of the control. The delivery of endocytosed HS proteoglycans to lysosomes were not affected by the drug. Cycloheximide also reduced the endocytosis of HS proteoglycans, but not as much as BFA, indicating that the inhibitory effect of BFA can be only partly accounted for by a block of protein transport from the endoplasmic reticulum to the plasma membrane. In contrast with the endocytosis of HS proteoglycans, neither that of I-125-transferrin, known to be mediated by clathrin-coated vescicles, nor that of I-125-ricin, a marker molecule for bulk endocytosis, was affected by BFA. The half-life of I-125-transferrin and I-125-ricin in the plasma membrane was about 10 and 25 min respectively compared with about 5 h for the HS proteoglycans. Altogether, these results indicate that the endocytosis of plasma-membrane-associated HS proteoglycans is mediated by different mechanisms than the endocytosis of most other cell-surface proteins. Further, the mechanisms involved in the endocytosis of HS proteoglycans are sensitive to BFA. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP UHLINHANSEN, L (reprint author), UNIV TROMSO,INST MED BIOL,POB 977,N-9037 TROMSO,NORWAY. NR 45 TC 14 Z9 14 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 AUG 15 PY 1995 VL 310 BP 271 EP 278 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN733 UT WOS:A1995RN73300038 PM 7646455 ER PT J AU ALI, N DUDEN, R BEMBENEK, ME SHEARS, SB AF ALI, N DUDEN, R BEMBENEK, ME SHEARS, SB TI THE INTERACTION OF COATOMER WITH INOSITOL POLYPHOSPHATES IS CONSERVED IN SACCHAROMYCES-CEREVISIAE SO BIOCHEMICAL JOURNAL LA English DT Article ID TRANSPORT; HEXAKISPHOSPHATE; PURIFICATION; TURNOVER; COMPLEX; BINDING; YEAST AB Coatomer is an oligomeric complex of coat proteins that regulates vesicular traffic through the Golgi complex and from the Golgi to the endoplasmic reticulum [Pelham (1994) Cell 79, 1125-1127]. We have investigated whether the binding of InsP(6) to mammalian coatomer [Fleischer, Xie, Mayrleitner, Shears and Fleischer (1994) J. Biol. Chem. 269, 17826-17832] is conserved in the genetically amenable model Saccharomyces cerevisiae. We have isolated coatomer from S. cerevisiae and found it to bind InsP, at two apparent classes of binding sites (K-D1 = 0.8+/-0.2nM; K-D2=361+/-102nM). Ligand specificity was studied by displacing 4.5 nM [H-3]InsP(6) from coatomer with various Ins derivatives. The following IC50 values (nM) were obtained: myo InsP(6)=6; bis(diphospho)inositol tetrakisphosphate=6; diphosphoinositol pentakisphosphate=6; scyllo-InsP(6) =12; Ins(1,3,4,5,6)P-5=13; Ins(1,2,4,5,6)P-5=22; Ins(1,3,4,5)P-4=22; 1-0-(1,2-di-0-octanoyl-sn-glycero-3-phospho)- D-Ins(3,4,5)P-3=290. Less than 10% of the H-3 label was displaced by 1 mu M of either Ins(1,4,5)P-3 or inositol hexakis-sulphate. A cell-free lysate of S. cerevisiae synthesized diphosphoinositol polyphosphates (PP-InsP(2)) from InsP(6), but our binding data, plus measurements of the relative levels of inositol polyphosphates in intact yeast [Hawkins, Stephens and Piggott (1993) J. Biol. Chem. 268, 3374-3383], indicate that InsP(6) is the major physiologically relevant ligand. Thus a reconstituted vesicle trafficking system using coatomer and other functionally related components isolated from yeast should be a useful model for elucidating the functional significance of the binding of InsP(6) by coatomer. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. UNIV CALIF BERKELEY,HOWARD HUGHES MED INST,DEPT MOLEC & CELLULAR BIOL,BERKELEY,CA 94720. DUPONT CO INC,DEPT MED PROD,NEW ENGLAND NUCL,BOSTON,MA 02118. RI Duden, Rainer/C-8917-2011 NR 26 TC 40 Z9 40 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 15 PY 1995 VL 310 BP 279 EP 284 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN733 UT WOS:A1995RN73300039 PM 7646456 ER PT J AU DIBRINO, M PARKER, KC MARGULIES, DH SHILOACH, J TURNER, RV BIDDISON, WE COLIGAN, JE AF DIBRINO, M PARKER, KC MARGULIES, DH SHILOACH, J TURNER, RV BIDDISON, WE COLIGAN, JE TI IDENTIFICATION OF THE PEPTIDE BINDING MOTIF FOR HLA-B44, ONE OF THE MOST COMMON HLA-B ALLELES IN THE CAUCASIAN POPULATION SO BIOCHEMISTRY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; VIRUS MATRIX PEPTIDE; HISTOCOMPATIBILITY ANTIGEN; ENDOGENOUS PEPTIDES; VIRAL PEPTIDES; MHC; MOLECULES; RECOGNITION; RESOLUTION; COMPLEXES AB Most peptides that bind to a particular MHC class I molecule share amino acid residues that are thought to physically ''anchor'' the peptide to polymorphic pockets within the class I binding site. Sequence analysis of endogenous peptides bound to HLA-B44 revealed two potential dominant anchor residues: Glu at P2 and Tyr, or occasionally Phe, at P9. In vitro assembly assays employing synthetic peptides and recombinant HLA-B44 produced by Escherichia coli revealed that an acidic amino acid at P2 was necessary for promoting stable peptide binding to HLA-B44. Surprisingly, although Tyr was almost exclusively found at p9 of the endogenous peptide sequences, a wide variety of amino acid residues such as Leu, Ala, Arg, Lys, His, and Phe could be tolerated at this position. Using this information, we identified antigenic peptides from the influenza virus components nonstructural protein I and nucleoprotein that are presented by HLA-B44 to antiinfluenza type A cytotoxic T lymphocytes. In addition, cytotoxic T lymphocytes induced by these antigenic peptides were shown to be capable of recognizing endogenously processed peptides from influenza-infected cells, indicating a potential use for these peptides in vaccine development. Finally, molecular models were created to investigate the possible ways in which the anchor residues might function to stabilize the binding of peptides to HLA-B44, and these models indicate that the acidic residue at P2 most likely interacts primarily with Lys 45 of the HLA-B44 heavy chain and makes additional contacts with Ser 67 and Tyr 9. C1 NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375; Parker, Kenneth/0000-0002-6282-2478 NR 48 TC 54 Z9 55 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 15 PY 1995 VL 34 IS 32 BP 10130 EP 10138 DI 10.1021/bi00032a005 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RP771 UT WOS:A1995RP77100005 PM 7543776 ER PT J AU LIPSKA, BK JASKIW, GE BRAUN, AR WEINBERGER, DR AF LIPSKA, BK JASKIW, GE BRAUN, AR WEINBERGER, DR TI PREFRONTAL CORTICAL AND HIPPOCAMPAL MODULATION OF HALOPERIDOL-INDUCED CATALEPSY AND APOMORPHINE-INDUCED STEREOTYPIC BEHAVIORS IN THE RAT SO BIOLOGICAL PSYCHIATRY LA English DT Article DE PREFRONTAL CORTEX; HIPPOCAMPUS; STEREOTYPY; CATALEPSY; APOMORPHINE; HALOPERIDOL; DOPAMINE ID IBOTENIC ACID LESIONS; NUCLEUS-ACCUMBENS; INDUCED LOCOMOTION; DOPAMINE; CORTEX; AMPHETAMINE; BLOCKADE; METABOLITES; ANTAGONIST; RESPONSES AB Effects of prefrontal cortical or hippocampal excitotoxic lesions on behavioral parameters related to dopaminergic transmission in the basal ganglia were investigated in the vat. We examined haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors after ibotenic acid lesions of the medial prefrontal cortex (MPFC), dorsal (DH), or ventral hippocampus (VH) in adult rats. Haloperidol-induced (I mg/kg) catalepsy was decreased in rats with either MPFC or VH but nob DH lesions. While both DH and VH lesioned animals demonstrated a reduction in apomorphine-induced (0.75 mg/kg) stereotypic behaviors, the VH lesioned animals also showed an enhancement of locomotor activity. MPFC lesioned rats tended towards potentiation of stereotypic behaviors and reduced locomotion after apomorphine administration, These data indicate that loss of prefrontal cortical or hippocampal modulation leads to an enhancement of DA transmission within the basal ganglia, though the pattern of augmentation depends on the area lesioned. RP LIPSKA, BK (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,2700 MARTIN LUTHER KING JR,AVE SE,WASHINGTON,DC 20032, USA. NR 39 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD AUG 15 PY 1995 VL 38 IS 4 BP 255 EP 262 DI 10.1016/0006-3223(94)00261-Z PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RR145 UT WOS:A1995RR14500008 PM 8547448 ER PT J AU MASON, DY CORDELL, JL BROWN, MH BORST, J JONES, M PULFORD, K JAFFE, E RALFKIAER, E DALLENBACH, F STEIN, H PILERI, S GATTER, KC AF MASON, DY CORDELL, JL BROWN, MH BORST, J JONES, M PULFORD, K JAFFE, E RALFKIAER, E DALLENBACH, F STEIN, H PILERI, S GATTER, KC TI CD79A - A NOVEL MARKER FOR B-CELL NEOPLASMS IN ROUTINELY PROCESSED TISSUE SAMPLES SO BLOOD LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; PARAFFIN-EMBEDDED TISSUES; MONOCLONAL-ANTIBODIES; IMMUNOHISTOLOGICAL DETECTION; LYMPHOBLASTIC-LEUKEMIA; SIGNAL-TRANSDUCTION; LYMPHOCYTE-B; MB-1; IGM; SECTIONS AB The CD79 molecule, comprising two polypeptide chains, mb-1 (CD79a) and B29 (CD79b), is physically associated in the B-cell membrane with immunoglobulin. It transmits a signal after antigen binding and may, therefore, be considered the B cell equivalent of CD3. It appears before the pre-B-cell stage, and the mb-1 (CD79a) chain can still be present at the plasma cell stage. In this report, we describe a new anti-CD79a monoclonal antibody, JCB117, which reacts with human B cells in paraffin embedded tissue sections, including decalcified bone marrow trephines. When tested on a total of 454 paraffin embedded tissue biopsies, gathered from a number of different institutions, it reacted with the great majority (97%) of B-cell neoplasms, covering the full range of B-cell maturation, including 10 of 20 cases of myeloma/ plasmacytoma. It is of interest that the antibody labels precursor B-cell acute lymphoblastic leukemia samples, making it the most reliable B-cell marker detectable in paraffin-embedded specimens in this disorder. All neoplasms of T cell or nonlymphoid origin were negative, indicating that antibody JCB117 may be of value to diagnostic histopathologists for the identification of B-cell neoplasms of all maturation stages. (C) 1995 by The American Society of Hematology. C1 SIR WILLIAM DUNN SCH PATHOL,MRC,CELLULAR IMMUNOL UNIT,OXFORD,ENGLAND. NETHERLANDS CANC INST,DIV CELLULAR BIOCHEM,1066 CX AMSTERDAM,NETHERLANDS. NCI,PATHOL LAB,BETHESDA,MD 20892. FREE UNIV BERLIN,STEGLITZ UNIV CLIN,INST PATHOL,W-1000 BERLIN,GERMANY. ST ORSOLA POLYCLIN,HAEMOLYMPHOPATHOL HISTOL SECT,BOLOGNA,ITALY. RP MASON, DY (reprint author), UNIV OXFORD,JOHN RADCLIFFE HOSP,DEPT CELLULAR SCI,LRF IMMUNODIAGNOST UNIT,OXFORD OX3 9DU,ENGLAND. RI Cordell, Jacqueline/B-3430-2009; Pulford, Karen/B-3609-2009 OI Pulford, Karen/0000-0002-2989-789X NR 41 TC 121 Z9 123 U1 0 U2 3 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 AUG 15 PY 1995 VL 86 IS 4 BP 1453 EP 1459 PG 7 WC Hematology SC Hematology GA RN467 UT WOS:A1995RN46700029 PM 7632952 ER PT J AU KANG, YK ZHAN, ZR REGIS, J ROBEY, R MEADOWS, B DICKSTEIN, B LEE, JS OTSUKI, T STETLERSTEVENSON, M JAFFE, ES SOLOMON, D WILSON, WH FOJO, A BATES, SE AF KANG, YK ZHAN, ZR REGIS, J ROBEY, R MEADOWS, B DICKSTEIN, B LEE, JS OTSUKI, T STETLERSTEVENSON, M JAFFE, ES SOLOMON, D WILSON, WH FOJO, A BATES, SE TI EXPRESSION OF MDR-1 IN REFRACTORY LYMPHOMA - QUANTITATION BY POLYMERASE CHAIN-REACTION AND VALIDATION OF THE ASSAY SO BLOOD LA English DT Article ID MULTIDRUG-RESISTANCE GENE; GLUTATHIONE-S-TRANSFERASE; DIFFUSE LARGE-CELL; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; P-GLYCOPROTEIN; BETA-2 MICROGLOBULIN; IMMUNOHISTOCHEMICAL DETECTION; MALIGNANT-LYMPHOMA; PERIPHERAL-BLOOD AB Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an important tool for assessing the impact of multidrug resistance in clinical cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction (PCR) assay in 78 biopsy samples from 48 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH) in which R-verapamil was added as an antagonist of P-glycoprotein in a subset of patients whose tumors were unresponsive to treatment. Expression of mdr-1 was detectable in all biopsies at the time of enrollment on study, and a fourfold or greater increase in mdr-1 expression was noted in 42% of patients at the time of treatment failure. Expression of mdr-1 was also detectable in biopsies from patients at the time of diagnosis of lymphoma. An endogenous control gene, beta(2)-microglobulin, was quantitated for normalization of the mdr-1 values. The use of beta(2)-microglobulin expression for normalization was validated in a subset of samples by comparing Northern blots detecting beta(2)-microglobulin, beta-actin, and GAPDH gene expression. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein level. Immunophenotyping of lymphomatous lymph nodes showed that infiltration of tumor cells ranged from 8% to 95% and of normal T cells from 1% to 83%. Expression of mdr-1 in normal T cells and monocytes was also shown to be low. The mdr-1 levels in patient samples were independent of T-cell contamination, suggesting that the presence of normal cells has at best a small impact on mdr-1 measurements. Expression of mdr-1 in lymphoma can be quantitated by PCR, and wide variations in expression can be observed. Increased expression in patients with refractory disease supports an important role for Pgp in drug resistance in lymphoma. These studies will aid in the design and interpretation of clinical trials in lymphoma. C1 NCI, DIV CANC TREATMENT, MED BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC BIOL DIAG & CTR, BETHESDA, MD 20892 USA. KOREA CANC CTR HOSP, DIV HEMATOL ONCOL, SEOUL, SOUTH KOREA. NR 49 TC 46 Z9 49 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 15 PY 1995 VL 86 IS 4 BP 1515 EP 1524 PG 10 WC Hematology SC Hematology GA RN467 UT WOS:A1995RN46700037 PM 7632959 ER PT J AU YANG, JC TOPALIAN, SL SCHWARTZENTRUBER, DJ PARKINSON, DR MARINCOLA, FM WEBER, JS SEIPP, CA WHITE, DE ROSENBERG, SA AF YANG, JC TOPALIAN, SL SCHWARTZENTRUBER, DJ PARKINSON, DR MARINCOLA, FM WEBER, JS SEIPP, CA WHITE, DE ROSENBERG, SA TI THE USE OF POLYETHYLENE GLYCOL-MODIFIED INTERLEUKIN-2 (PEG-IL-2) IN THE TREATMENT OF PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA AND MELANOMA - A PHASE-I STUDY AND A RANDOMISED PROSPECTIVE STUDY COMPARING IL-2 ALONE VERSUS IL-2 COMBINED WITH PEG-IL-2 SO CANCER LA English DT Article DE IMMUNOTHERAPY; CYTOKINES; RENAL CELL CARCINOMA; MELANOMA; POLYETHYLENE GLYCOL; INTERLEUKIN-2; POLYETHYLENE GLYCOL-MODIFIED INTERLEUKIN-2 ID DOSE RECOMBINANT INTERLEUKIN-2; CIRCULATING LIFE; MURINE; COMBINATION; ATTACHMENT; CANCER AB Background. Conjugation of polyethylene glycol to recombinant human interleukin-2 (IL-2) results in a compound, polyethylene glycol-modified IL-2 (PEG-IL-2) that retains the in vitro and in vivo activity of IL-2, but exhibits a markedly prolonged circulating half-life. In mice, one dose of PEG-IL-2 results in tumor regression comparable to that achieved with multiple bolus doses of IL-2. Based on these preclinical studies, a Phase I study with PEG-IL-I was undertaken in patients with metastatic renal cell carcinoma (RCC) and melanoma, Then, to exploit the higher peak levels attained with IL-2 and the improved trough levels of PEG-IL-2, a combination regimen beginning with bolus IL-2 followed by low dose maintenance PEG-IL-8 was devised and tested for efficacy. Methods. Patients with measurable metastatic melanoma or RCC were entered in a Phase I dose escalation trial of PEG-IL-2 given once a week by intravenous bolus. This trial then was repeated using a twice-a-week schedule. After determining the maximum tolerated dose (MTD) and a safe outpatient regimen for PEG-IL-2, a hybrid regimen combining an initial high dose IL-2 cycle followed by chronic maintenance with weekly PEG-IL-2 was devised. This regimen was compared with a standard regimen consisting of two cycles of high dose unconjugated IL-2 in a randomized prospective clinical trial. Results. When given by intravenous bolus once a week, the MTD of PEG-IL-2 was 12 million IU/m(2), with toxicities similar to those of unconjugated IL-2. A twice-a-week schedule was less well tolerated. Of 28 patients given 32 treatment courses at varied dose levels, there were two partial responses and one minor response, A total of 124 patients with metastatic melanoma or RCC were randomized to either standard unconjugated IL-2 therapy or the hybrid regimen. There was no treatment-related mortality in either arm, and the use of PEG-IL-2 resulted in a significant decrease in the need for intensive-care-unit care. The response rates (partial response and complete response) for patients with RCC and melanoma were 19% and 15%, respectively, for IL-2 alone and 17% and 11%, respectively, for the IL-2 and PEG-IL-2 combination. Conclusions. The combination of high dose IL-2 followed by PEG-IL-2 is a well tolerated regimen with significant activity against RCC and melanoma, but it shows no significant increase in antitumor activity compared with high dose IL-2 alone. RP YANG, JC (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B-37,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 39 Z9 39 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 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1995 VL 76 IS 4 BP 687 EP 694 DI 10.1002/1097-0142(19950815)76:4<687::AID-CNCR2820760424>3.0.CO;2-M PG 8 WC Oncology SC Oncology GA RN418 UT WOS:A1995RN41800023 PM 8625167 ER PT J AU AMBROSONE, CB FREUDENHEIM, JL GRAHAM, S MARSHALL, JR VENA, JE BRASURE, JR LAUGHLIN, R NEMOTO, T MICHALEK, AM HARRINGTON, A FORD, TD SHIELDS, PG AF AMBROSONE, CB FREUDENHEIM, JL GRAHAM, S MARSHALL, JR VENA, JE BRASURE, JR LAUGHLIN, R NEMOTO, T MICHALEK, AM HARRINGTON, A FORD, TD SHIELDS, PG TI CYTOCHROME P4501A1 AND GLUTATHIONE-S-TRANSFERASE (M1) GENETIC POLYMORPHISMS AND POSTMENOPAUSAL BREAST-CANCER RISK SO CANCER RESEARCH LA English DT Note ID EPITHELIAL-CELLS; SUSCEPTIBILITY; METABOLISM; GSTM1; LUNG; TRANSFORMATION; BLADDER AB Polycyclic aromatic hydrocarbons, possible human breast carcinogens, are metabolized by cytochrome P4501A1 (CYP1A1) and glutathione S-transferase (GSTM1), A CYP1A1 polymorphism (isoleucine to valine substitution in exon 7) or the null allele for GSTM1 may affect the mutagenic potential of polycyclic aromatic hydrocarbons. We examined polymorphisms in GSTM1 and CYP1A1 in relation to breast cancer risk. Included were 216 postmenopausal Caucasian women with incident breast cancer and 282 community controls. DNA analyses suggested no increased breast cancer risk with the null GSTM1 genotype [odds ratio (OR) = 1.10; CI, 0.73-1.61], although there was some indication that the null genotype was associated with risk among the youngest postmenopausal women (OR = 2.44; CI, 0.89-6.64). Slightly elevated risk was associated with the CYP1A1 polumorphism (OR = 1.61; CI, 0.94-2.79 and was highest for those who smoked up to 29 pack-years (OR = 5.22; CI, 1.16-23.56). Statistical power to detect an effect may be limited by small numbers, and larger sample sizes would be required to corroborate these suggestive findings. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP AMBROSONE, CB (reprint author), SUNY BUFFALO,DEPT SOCIAL & PREVENT MED,270 FARBER HALL,BUFFALO,NY 14214, USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA-01633, CA-11535, CA-62995] NR 23 TC 183 Z9 190 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1995 VL 55 IS 16 BP 3483 EP 3485 PG 3 WC Oncology SC Oncology GA RN654 UT WOS:A1995RN65400004 PM 7627950 ER PT J AU BELL, DA STEPHENS, EA CASTRANIO, T UMBACH, DM WATSON, M DEAKIN, M ELDER, J HENDRICKSE, C DUNCAN, H STRANGE, RC AF BELL, DA STEPHENS, EA CASTRANIO, T UMBACH, DM WATSON, M DEAKIN, M ELDER, J HENDRICKSE, C DUNCAN, H STRANGE, RC TI POLYADENYLATION POLYMORPHISM IN THE ACETYLTRANSFERASE-1 GENE (NAT1) INCREASES RISK OF COLORECTAL-CANCER SO CANCER RESEARCH LA English DT Article ID ARYLAMINE N-ACETYLTRANSFERASE; METABOLIC-ACTIVATION; ACETYLATION; CARCINOGENS; HUMANS; COMMON AB Exposure to carcinogens present in the diet, cigarette smoke, or the environment may be associated with increased risk of colorectal cancer, Aromatic amines (aryl- and heterocyclic) are a class of carcinogens that are important in these exposures. These compounds can be N- or O-acetylated by the NAT1 or NAT2 enzymes, resulting in activation or in some cases detoxification. Recent studies have shown that both NAT2 and NAT1 genes exhibit variation in human populations and that rapid acetylation by the NAT2 enzyme may be a risk factor for colorectal cancer. In this study we have analyzed for genetic polymorphism in both NAT1 and NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from Staffordshire, England. We find significantly increased risk (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = 0.009) associated with the NAT1*10 allele of NAT1, an allele that contains a variant polyadenylation signal, Individuals with higher stage tumors (Duke's C) were more likely to inherit this variant allele (odds ratio, 2.5; 95% confidence interval, 1.3-4.7; P = 0.005). In contrast, rapid acetylation genotypes of NAT2 were not a significant risk factor in this English population. However,we found that the risk associated with the NAT1 variant allele (NAT1*10) was most apparent among NAT2 rapid acetylators (odds ratio, 2.8; 95% confidence interval, 1.4-5.7; P = 0.003), suggesting a possible gene-gene interaction between NAT1 and NAT2 (test for interaction; P = 0.12). This is the first study to test for cancer risk associated with the NAT1 gene, and these positive findings suggest that NAT1 alleles may be important genetic determinents of colorectal cancer risk. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. KEELE UNIV,N STAFFORDSHIRE HOSP,POSTGRAD MED SCH,DEPT SURG,STOKE ON TRENT,STAFFS,ENGLAND. KEELE UNIV,N STAFFORDSHIRE HOSP,POSTGRAD MED SCH,CLIN BIOCHEM RES LAB,STOKE ON TRENT TS4 7QB,STAFFS,ENGLAND. RP BELL, DA (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,C3-03,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 218 Z9 224 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1995 VL 55 IS 16 BP 3537 EP 3542 PG 6 WC Oncology SC Oncology GA RN654 UT WOS:A1995RN65400016 PM 7627961 ER PT J AU CHIAO, C CAROTHERS, AM GRUNBERGER, D SOLOMON, G PRESTON, GA BARRETT, JC AF CHIAO, C CAROTHERS, AM GRUNBERGER, D SOLOMON, G PRESTON, GA BARRETT, JC TI APOPTOSIS AND ALTERED REDOX STATE INDUCED BY CAFFEIC ACID PHENETHYL ESTER (CAPE) IN TRANSFORMED RAT FIBROBLAST CELLS SO CANCER RESEARCH LA English DT Article ID INHIBITION; ACTIVATION; SURVIVAL; AGENTS; DEATH; P53 AB Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of bee hives, was shown previously to block tumor promoter- and carcinogen-generated oxidative processes in several assays and to engender differential toxicity to some transformed cells. To study the mechanisms of CAPE-induced differential cytotoxicity, nontumorigenic rat embryo fibroblasts (CREF) and adenovirus (type 5)-transformed CREF cells (Wt3A) were used. As shown by nucleosomal-length DNA degradation, morphological alterations by electron microscopy, in situ labeling of 3'-OH ends, and the appearance of a hypodiploid cell population by bivariant flow cytometry, cell death induced by CAFE in the transformed Wt3A cells was apoptosis. Under the same CAFE treatment condition, CREF cells transiently growth arrested. Both CREF and Wt3A cells were radioresistant, suggesting deficiencies in the proteins controlling the G(1) checkpoint. To explore possible mechanisms of CAPE-induced apoptosis, it was determined whether CAPE-induced toxicity was influenced by the redox state of the cells, Depletion of cellular glutathione (GSH) with buthionine sulfoximine before CAPE treatment caused CREF sensitive to CAPE-induced cell death. GSH levels were also determined in CAPE-treated CREF and Wt3A cells. The GSH level in the CREF cells was unaffected by CAPE, whereas the Wt3A cells showed a significant reduction. When the GSH levels were increased in Wt3A cells by treatment with the reducing agent, N-acetyl-cysteine before CAPE treatment, the Wt3A cells were partially rescued. Furthermore, Bcl2, which protects cells from oxidative stress, had a protective effect against CAPE-induced apoptosis in Wt3A cells. Finally, the sensitivity of Wt3A cells to a known oxidant, hydrogen peroxide (H2O2), was examined. Wt3A cells were killed by H2O2-induced apoptosis, whereas CREF cells remained resistant. When Wt3A cells were treated with catalase, a cellular enzyme that inactivates H2O2, CAPE-induced apoptosis in Wt3A cells was reduced, further proving that Wt3A cells were more sensitive than CREF cells to oxidative stress. These results suggest that CAPE can modulate the redox state of cells. Sensitivity of cells to CAPE-induced cell death may be determined by the loss of normal redox state regulation in transformed cells. C1 COLUMBIA UNIV COLL PHYS & SURG,COLUMBIA PRESBYTERIAN CANC CTR,CANC RES INST,NEW YORK,NY 10032. COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10032. RP CHIAO, C (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 149 Z9 152 U1 0 U2 6 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 AUG 15 PY 1995 VL 55 IS 16 BP 3576 EP 3583 PG 8 WC Oncology SC Oncology GA RN654 UT WOS:A1995RN65400022 PM 7543016 ER PT J AU HODGE, JW MCLAUGHLIN, JP ABRAMS, SI SHUPERT, WL SCHLOM, J KANTOR, JA AF HODGE, JW MCLAUGHLIN, JP ABRAMS, SI SHUPERT, WL SCHLOM, J KANTOR, JA TI ADMIXTURE OF A RECOMBINANT VACCINIA VIRUS CONTAINING THE GENE FOR THE COSTIMULATORY MOLECULE B7 AND A RECOMBINANT VACCINIA VIRUS CONTAINING A TUMOR-ASSOCIATED ANTIGEN GENE RESULTS IN ENHANCED SPECIFIC T-CELL RESPONSES AND ANTITUMOR IMMUNITY SO CANCER RESEARCH LA English DT Article ID LYMPHOCYTES-T; EXPRESSION; CD28; CYTOTOXICITY; TRANSDUCTION AB At least two signals are required for the activation of naive T cells by antigen-bearing target cells: an antigen-specific signal, delivered through the T-cell receptor, and a costimulatory signal delivered through the T-cell surface molecule CD28 by its natural ligand B7-1. The immunological benefit of coexpression of B7 with target antigen has been demonstrated with the use of several retroviral systems to transfect antigen-hearing cells. Although engineering recombinant constructs with genes for two or more antigens can mediate the dual expression of those antigens, disadvantages of this approach include the time for construction of each desirable combination and the inability to control differential expression levels of each gene product. An alternative approach would utilize separate constructs that could be admixed appropriately before administration. In this report we describe the functional consequences of the admixture of recombinant vaccinia murine B7-1 (rV-B7) to recombinant vaccinia expressing the human carcinoembryonic antigen gene (rV-CEA). Coinfection of cells resulted in high levels of cell surface expression of both the CEA and B7 molecules. Immunization of mice with various ratios (1:3, 1:1, 3:1) of rV-CEA and rV-B7 demonstrated that an admixture of rV-CEA and rV-B7 at a 3:1 ratio resulted in the generation of optimal CEA-specific T-cell responses. Next, we examined the efficacy of this admixture on antitumor activity. Typically, injection of murine carcinoma cells expressing CEA leads to the death of the host. One immunization of C57BL/6 mice,vith rV-CEA:rV-B7 (3:1) resulted in no tumor establishment, In contrast, administration of rV-CEA or rV-B7 atone had little or no antitumor effects. These studies demonstrate the advantages of the use of recombinant vaccinia viruses to deliver B7 molecules in combination with a tumor-associated antigen. The availability of the rV-B7 single construct and the ability to alter the B7 ratio could also have potential utility when coinfecting rV-B7 with recombinant vaccinia viruses containing genes for infectious agents or other tumor-associated antigen genes. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 41 TC 85 Z9 88 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 AUG 15 PY 1995 VL 55 IS 16 BP 3598 EP 3603 PG 6 WC Oncology SC Oncology GA RN654 UT WOS:A1995RN65400025 PM 7543017 ER PT J AU FANANAPAZIR, L EPSTEIN, ND AF FANANAPAZIR, L EPSTEIN, ND TI PREVALENCE OF HYPERTROPHIC CARDIOMYOPATHY AND LIMITATIONS OF SCREENING METHODS SO CIRCULATION LA English DT Editorial Material DE EDITORIALS; HYPERTROPHY; CARDIOMYOPATHY ID HEAVY-CHAIN GENE; BETA-MYOSIN; MISSENSE MUTATIONS; EXPRESSION; MASS RP FANANAPAZIR, L (reprint author), NHLBI,CLIN ELECTROPHYSIOL LAB,CARDIOL BRANCH,INHERITED CARDIAC DIS SECT,BLDG 10,ROOM 7B-14,BETHESDA,MD 20892, USA. NR 25 TC 34 Z9 37 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1995 VL 92 IS 4 BP 700 EP 704 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RN852 UT WOS:A1995RN85200004 PM 7641346 ER PT J AU KULLER, LH SHEMANSKI, L PSATY, BM BORHANI, NO GARDIN, J HAAN, MN OLEARY, DH SAVAGE, PJ TELL, GS TRACY, R AF KULLER, LH SHEMANSKI, L PSATY, BM BORHANI, NO GARDIN, J HAAN, MN OLEARY, DH SAVAGE, PJ TELL, GS TRACY, R TI SUBCLINICAL DISEASE AS AN INDEPENDENT RISK FACTOR FOR CARDIOVASCULAR-DISEASE SO CIRCULATION LA English DT Article DE CARDIOVASCULAR DISEASES; MORBIDITY; MORTALITY; RISK FACTORS; AGING ID CORONARY HEART-DISEASE; UNRECOGNIZED MYOCARDIAL-INFARCTION; BLOOD-PRESSURE INDEX; ARTERIAL-DISEASE; FOLLOW-UP; MORTALITY; ATHEROSCLEROSIS; CHOLESTEROL; HEALTH; OLDER AB Background The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study. Methods and Results A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes. Conclusions The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease. C1 UNIV WASHINGTON,SCH MED,SEATTLE,WA. UNIV CALIF IRVINE,DIV CARDIOL,DAVIS,CA. UNIV CALIF SACRAMENTO,DEPT INTERNAL MED,SACRAMENTO,CA. GEISINGER MED CTR,DIV RADIOL,DANVILLE,PA 17822. NHLBI,DECA,BETHESDA,MD. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV VERMONT,DEPT PATHOL BIOCHEM,COLCHESTER,VT. RP KULLER, LH (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,130 DESOTO ST,PITTSBURGH,PA 15261, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 NR 46 TC 211 Z9 218 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1995 VL 92 IS 4 BP 720 EP 726 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RN852 UT WOS:A1995RN85200007 PM 7641349 ER PT J AU MARON, BJ GARDIN, JM FLACK, JM GIDDING, SS KUROSAKI, TT BILD, DE AF MARON, BJ GARDIN, JM FLACK, JM GIDDING, SS KUROSAKI, TT BILD, DE TI PREVALENCE OF HYPERTROPHIC CARDIOMYOPATHY IN A GENERAL-POPULATION OF YOUNG-ADULTS - ECHOCARDIOGRAPHIC ANALYSIS OF 4111 SUBJECTS IN THE CARDIA STUDY SO CIRCULATION LA English DT Article DE CARDIOMYOPATHY; ECHOCARDIOGRAPHY; HYPERTROPHY ID LEFT-VENTRICULAR HYPERTROPHY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; SYSTOLIC ANTERIOR MOTION; M-MODE ECHOCARDIOGRAPHY; SUDDEN-DEATH; CLINICAL MANIFESTATIONS; CARDIOVASCULAR-DISEASE; PATHO-PHYSIOLOGY; PATTERNS; PROGNOSIS AB Background Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease and an important cause of morbidity and sudden cardiac death in young people, including competitive athletes. At present, however, few data exist to estimate the prevalence of this disease in large populations. Methods and Results As part of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Study, an epidemiological study of coronary risk factors, 4111 men and women 23 to 35 years of age selected from the general population of four urban centers had technically satisfactory echocardiographic studies during 1987 through 1988. Probable or definite echocardiographic evidence of HCM was present in 7 subjects (0.17%) on the basis of identification of a hypertrophied, nondilated left ventricle and maximal wall thickness greater than or equal to 15 mm that were not associated with systemic hypertension. Prevalence in men and women was 0.26:0.09%; in blacks and whites, 0.24:0.10%. Ventricular septal thickness was 15 to 21 mm (mean, 17 mm) in the 7 subjects. Only 1 of the 7 subjects had ever experienced important cardiac symptoms attributable to HCM, had previously been suspected of having cardiovascular disease, or had obstruction to left ventricular outflow; 4 other subjects had relatively mild systolic anterior motion of the mitral valve that was insufficient to produce dynamic basal outflow obstruction. ECGs were abnormal in 5 of the 7 subjects. Five other study subjects had left ventricular wall thicknesses of 15 to 21 mm that were a consequence of systemic hypertension. Conclusions HCM was present in about 2 of 1000 young adults. These unique population-based data will aid in assessments of the impact of HCM-related mortality and morbidity in the general population and the practicality of screening large populations for HCM, including those comprising competitive athletes. C1 UNIV CALIF IRVINE,IRVINE MED CTR,DIV CARDIOL,ORANGE,CA 92668. UNIV CALIF IRVINE,IRVINE MED CTR,DIV EPIDEMIOL,ORANGE,CA 92668. UNIV MINNESOTA,SCH MED,DIV GEN & PREVENT MED,MINNEAPOLIS,MN 55455. NORTHWESTERN UNIV,SCH MED,DIV PEDIAT CARDIOL,CHICAGO,IL. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP MARON, BJ (reprint author), MINNEAPOLIS HEART INST FDN,DIV CARDIOVASC RES,920 E 28TH ST,STE 40,MINNEAPOLIS,MN 55407, USA. FU NHLBI NIH HHS [N01-HC-95095, N01-HC-48047, N01-HC-48050] NR 44 TC 876 Z9 951 U1 3 U2 24 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1995 VL 92 IS 4 BP 785 EP 789 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RN852 UT WOS:A1995RN85200016 PM 7641357 ER PT J AU BENJAMIN, EJ DAGOSTINO, RB BELANGER, AJ WOLF, PA LEVY, D AF BENJAMIN, EJ DAGOSTINO, RB BELANGER, AJ WOLF, PA LEVY, D TI LEFT ATRIAL SIZE AND THE RISK OF STROKE AND DEATH - THE FRAMINGHAM HEART-STUDY SO CIRCULATION LA English DT Article DE ECHOCARDIOGRAPHY; CEREBROVASCULAR; DISORDERS; HEART ATRIUM; HYPERTROPHY; RISK FACTORS; MORTALITY ID MITRAL-VALVE DISEASE; SYSTEMIC EMBOLISM; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; FIBRILLATION; EMBOLIZATION AB Background The medical literature contains conflicting reports on the association of left atrial (LA) enlargement with risk of stroke. The relation of LA size to risk of stroke and death in the general population remains largely unexplored. Methods and Results Subjects 50 years of age and older from the Framingham Heart Study were studied to assess the relations between echocardiographic LA size and risk of stroke and death. During 8 years of follow-up, 64 of 1371 (4.7%) men and 73 of 1728 (4.2%) women sustained a stroke, and 296 (21.6%) men and 271 (15.7%) women died. Sex-specific Cox proportional-hazards models were adjusted for age, hypertension, diabetes, atrial fibrillation, smoking, ECG left ventricular (LV) hypertrophy, and congestive heart failure or myocardial infarction. After multivariable adjustment, for every 10-mm increase in LA size, the relative risk of stroke was 2.4 in men (95% CI, 1.6 to 3.7) and 1.4 in women (95% CI, 0.9 to 2.1); the relative risk of death was 1.3 in men (95% CI, 1.0 to 1.5) and 1.4 in women (95% CI, 1.1 to 1.7). Adjusting for ECG LV mass/height attenuated the relation of LA size to stroke and death. Conclusions After multivariable adjustment, LA enlargement remained a significant predictor of stroke in men and death in both sexes. The relation of LA enlargement to stroke and death appears to be partially mediated by LV mass. C1 BOSTON UNIV,SCH MED,DEPT CARDIOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02118. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CARDIOL & CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. RP BENJAMIN, EJ (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [2-R01-NS-17950-11] NR 48 TC 524 Z9 548 U1 2 U2 11 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1995 VL 92 IS 4 BP 835 EP 841 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RN852 UT WOS:A1995RN85200023 PM 7641364 ER PT J AU BRENDLER, T ABELES, A AUSTIN, S AF BRENDLER, T ABELES, A AUSTIN, S TI A PROTEIN THAT BINDS TO THE P1 ORIGIN CORE AND THE ORIC 13MER REGION IN A METHYLATION-SPECIFIC FASHION IS THE PRODUCT OF THE HOST SEQA GENE SO EMBO JOURNAL LA English DT Article DE METHYLATION; ORIC; P 1 ORIR; REPLICATION; SEQUESTRATION ID ESCHERICHIA-COLI CHROMOSOME; REPLICATION ORIGIN; PLASMID REPLICATION; DNA-REPLICATION; DAM METHYLTRANSFERASE; NUCLEOTIDE-SEQUENCE; INITIATION; RECOGNITION; LOCATION; CLEAVAGE AB The P1 plasmid replication origin P1oriR is controlled by methylation of four GATC adenine methylation sites within heptamer repeats, A comparable (13mer) region is present in the host origin, oriC. The two origins show comparable responses to methylation; negative control by recognition of hemimethylated DNA (sequestration) and a positive requirement for methylation for efficient function, We have isolated a host protein that recognizes the P1 origin region only when it is isolated from a strain proficient for adenine methylation, The substantially purified 22 kDa protein also binds to the 13mer region of oriC in a methylation-specific fashion, It proved to be the product of the seqA gene that acts in the negative control of oriC by sequestration, We conclude that the role of the SeqA protein in sequestration is to recognize the methylation state of P1oriR and oriC by direct DNA binding, Using synthetic substrates we show that SeqA binds exclusively to the hemimethylated forms of these origins, forms that are the immediate products of replication in a methylation-proficient strain. We also show that the protein can recognize sequences with multiple GATC sites, irrespective of the surrounding sequence, The basis for origin specificity is primarily the persistence of hemimethylated forms that are over-represented in the natural DNA preparations relative to controls. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. NR 26 TC 80 Z9 80 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 AUG 15 PY 1995 VL 14 IS 16 BP 4083 EP 4089 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RQ669 UT WOS:A1995RQ66900024 PM 7664748 ER PT J AU WEISSMAN, D POLI, G FAUCI, AS AF WEISSMAN, D POLI, G FAUCI, AS TI IL-10 SYNERGIZES WITH MULTIPLE CYTOKINES IN ENHANCING HIV PRODUCTION IN CELLS OF MONOCYTIC LINEAGE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE IL-10; HIV; SYNERGY; INTERLEUKIN-6; TUMOR NECROSIS FACTOR; TRANSCRIPTIONAL ACTIVATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; INFECTED PROMONOCYTIC CELLS; PHORBOL-MYRISTATE ACETATE; NF-KAPPA-B; FACTOR-ALPHA; TYPE-1 INFECTION; T-CELLS; EXPRESSION AB Several cytokines, whose expression is increased in human immunodeficiency virus (HIV)-infected individuals, can enhance virus replication in CD4(+) T lymphocytes and mononuclear phagocytes (MP). We have previously reported that interleukin (IL)-10 inhibited HIV replication in acutely infected monocyte-derived macrophages (MDM) at concentrations that completely blocked the production of endogenous tumor necrosis factor-alpha (TNF-alpha) and IL-6 from infected cells. In the present study, lower concentrations of IL-10, which were unable to completely suppress endogenous cytokines, paradoxically enhanced HIV replication in MDM induced by other cytokines. This synergistic induction of HIV expression by IL-10 in combination with TNF-alpha, IL-6, and other cytokines was also observed in the chronically infected promonocytic cell line, U1. The enhancing effect of IL-10 was correlated with an increase in HIV mRNA accumulation and potentiation of phorbol ester-induced long terminal repeat-driven transcription that was independent of the NF-kappa B and Spl transcription factors. Thus, IL-10 is a cytokine capable of exerting complex regulatory effects on HIV expression in MP as a function of its own concentration and of the presence of other HIV regulatory cytokines. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 42 TC 75 Z9 75 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1995 VL 9 IS 5 BP 442 EP 449 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RM668 UT WOS:A1995RM66800002 PM 7627621 ER PT J AU BOEHME, SA ZHENG, LX LENARDO, MJ AF BOEHME, SA ZHENG, LX LENARDO, MJ TI ANALYSIS OF THE CD4 CORECEPTOR AND ACTIVATION-INDUCED COSTIMULATORY MOLECULES IN ANTIGEN-MEDIATED MATURE T-LYMPHOCYTE DEATH SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL CLONAL ANERGY; MONOCLONAL-ANTIBODY; APOPTOSIS; PROLIFERATION; B7/BB1; RECEPTOR; STIMULATION; EXPRESSION; INDUCTION; OCCURS AB We have compared the signaling requirements for activation and lymphokine production in mature T lymphocytes to those required for TCR-driven programmed cell death (PCD). Both processes require TCR engagement and ligation of the CD4 coreceptor in the case of a T cell clone that recognizes Ag in the context of an MHC class II molecule. By contrast, stimulation through the CD28/B7 pathway does not appear to positively or negatively influence TCR-induced PCD, although it was required for IL-2 production in both resting and proliferating T cells. T cells that had been activated and induced to proliferate with IL-2 were found to express high levels of IL-2 mRNA upon TCR rechallenge, without a requirement for accessory cells. This was due to a strong up-regulation of the B7-1 molecule, but not the B7-2 molecule, on the T cell surface. These T cells that strongly costimulate each other are highly susceptible to TCR-induced death providing independent evidence that costimulatory signals are not protective. Thus, these results provide evidence that in mature T cells there exists a difference in the requirement for CD28 to achieve activation and IL-2 production compared with TCR-mediated PCD. RP BOEHME, SA (reprint author), NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N311,10 CTR DR,MSC 1892,BETHESDA,MD 20892, USA. NR 47 TC 43 Z9 43 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 AUG 15 PY 1995 VL 155 IS 4 BP 1703 EP 1712 PG 10 WC Immunology SC Immunology GA RN464 UT WOS:A1995RN46400008 PM 7636229 ER PT J AU HAKIM, FT CEPEDA, R GRAY, GS JUNE, CH ABE, R AF HAKIM, FT CEPEDA, R GRAY, GS JUNE, CH ABE, R TI ACUTE GRAFT-VERSUS-HOST REACTION CAN BE ABORTED BY BLOCKADE OF COSTIMULATORY MOLECULES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; COLONY-STIMULATING FACTORS; INDUCED IMMUNE-DEFICIENCY; BONE-MARROW; CYTOKINE DYSREGULATION; PARENTAL LYMPHOCYTES; HYBRID RESISTANCE; CLONAL ANERGY; KILLER CELLS; IFN-GAMMA AB Injection of parental lymphocytes into an unirradiated adult F-1 host results in an acute GVH reaction characterized by immune deficiency, attack on host lymphohematopoietic tissues, and repopulation with donor-derived cells. All of these events result from the initial activation of donor lymphocytes by host alloantigens. Interaction of pairs of host and donor costimulatory molecules, in particular CD28/CTLA4 and B7-1/B7-2, play a crucial role in this initial activation of donor T cells. We demonstrate here that in vivo treatment of the host with high doses of CTLA4-Ig solely during the initial period of donor alloactivation can completely abort the subsequent development of GVH reaction. Although donor T cells are retained, CTLA4-Ig treatment reduces the initial endogenous cytokine production and arrests the subsequent expansion of donor T cells, the differentiation of anti-host effecters, and the development of severe immune deficiency. This result is consistent with the establishment of host-specific tolerance in the donor population, while maintaining host immune competence. C1 NATL MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20892. REPLIGEN CORP,CAMBRIDGE,MA 02139. RP HAKIM, FT (reprint author), NCI,MED BRANCH,TRANSPLANTAT THERAPY SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 55 TC 38 Z9 38 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 AUG 15 PY 1995 VL 155 IS 4 BP 1757 EP 1766 PG 10 WC Immunology SC Immunology GA RN464 UT WOS:A1995RN46400013 PM 7636232 ER PT J AU PALIOGIANNI, F HAMA, N BALOW, JE VALENTINE, MA BOUMPAS, DT AF PALIOGIANNI, F HAMA, N BALOW, JE VALENTINE, MA BOUMPAS, DT TI GLUCOCORTICOID-MEDIATED REGULATION OF PROTEIN-PHOSPHORYLATION IN PRIMARY HUMAN T-CELLS - EVIDENCE FOR INDUCTION OF PHOSPHATASE-ACTIVITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KINASE-II; CAM KINASE; AUTOPHOSPHORYLATION SITES; NUCLEAR TRANSCRIPTION; HUMAN INTERLEUKIN-2; AUTONOMOUS ENZYME; GENE-EXPRESSION; C-JUN; RECEPTOR; INHIBITION AB Glucocorticoid hormones (GC) have profound effects on the development and homeostasis of the immune system. In this communication we present evidence that GC regulate Ca2+-mediated pathways of T cell activation by a mechanism that involves abrogation of the autophosphorylation of the multifunctional Ca2+/calmodulin kinase (CaM kinase II) and induction of protein phosphatase activity. Primary human T cells were stimulated with the combination of ionomycin and phorbol ester in the presence or absence of dexamethasone (Dex) (10(-6)-10(-12) M). Stimulation of T cells resulted in a rapid activation of CaM kinase II and protein kinase C (PKC) activity as determined by the phosphorylation of synthetic peptide substrates recognized by these enzymes. Dex inhibited the activity of CaM kinase II but not PKC activity in a dose-dependent fashion (minimum effective dose 10(-10) M). Stimulation of P-32-labeled T cells induced a rapid increase in the phosphorylation level of CaM kinase II which was inhibited by Dex. The inhibitory effect of Dex on this enzyme was fully reversed in the presence of the phosphatase inhibitor okadaic acid (250 nM) or RU 486, a glucocorticoid antagonist. These results suggest that GC inhibit the activation of CaM kinase during T cell activation through a mechanism that involves both the GC receptor and protein phosphatases 2A and/or 1. Inhibition of protein phosphorylation through the induction of protein phosphatase activity may represent a novel mechanism for the diverse effects of GC on eukaryotic cells. C1 CELL THERAPEUT INC,SEATTLE,WA 98119. RP PALIOGIANNI, F (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N112,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM 42508] NR 50 TC 11 Z9 11 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 AUG 15 PY 1995 VL 155 IS 4 BP 1809 EP 1817 PG 9 WC Immunology SC Immunology GA RN464 UT WOS:A1995RN46400018 PM 7636235 ER PT J AU DIAZSANCHEZ, D ZHANG, K NUTMAN, TB SAXON, A AF DIAZSANCHEZ, D ZHANG, K NUTMAN, TB SAXON, A TI DIFFERENTIAL REGULATION OF ALTERNATIVE 3' SPLICING OF EPSILON-MESSENGER-RNA VARIANTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN B-CELLS; IGE PRODUCTION; IMMUNOGLOBULIN-E; INTERLEUKIN-4; LYMPHOCYTES; EXPRESSION; RECEPTOR; GENE; GENERATION; INDUCTION AB Alternative 3' splicing of the one active human epsilon heavy chain gene results in variants of epsilon mRNA encoding distinct IgE proteins. The same relative amounts of these < epsilon mRNA variants were produced by non-atopic donor B cells when driven in a variety of T-dependent or T-independent systems. The most abundant variants were those for classic secreted epsilon and a novel secreted form (CH4-M2''). In contrast, cells from subjects with high levels of serum IgE secondary to parasitic infection or atopy spontaneously produced higher relative levels of the CH4-M2' epsilon mRNA variant, lower relative amounts of both the membrane and CH4-M2'' secreted variants, and very low levels of the CH4'-CH5 variant. The existence of and corresponding changes in levels of the CH4-M2'-encoded secreted protein were demonstrated. IL-10 induced this same differential expression of epsilon splice variants in vitro when used to costimulate IL-4 plus CD40-driven B cells and could differentially enhance the production of CH4-M2' protein by established IgE-secreting cell lines. Inhibition of IgE by cross-linking the low affinity IgE receptor (CD23) decreased the levels of epsilon mRNA and resulted in a distinct pattern of epsilon mRNA characterized by a dramatic decrease in CH4-M2' splice variant. IL-6, IL-2, or IFN-gamma did not change the epsilon mRNA pattern. Overall, the absolute and relative amounts of the different epsilon mRNA splice variants produced appear to be controlled in a differentiation-related fashion. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV CLIN IMMUNOL & ALLERGY,HART & LOUISE LYON LAB,LOS ANGELES,CA 90024. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST MOLEC BIOL,LOS ANGELES,CA 90095. FU NIAID NIH HHS [AI-15251, AI-34567] NR 37 TC 18 Z9 18 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 AUG 15 PY 1995 VL 155 IS 4 BP 1930 EP 1941 PG 12 WC Immunology SC Immunology GA RN464 UT WOS:A1995RN46400030 PM 7636244 ER PT J AU DHIBJALBUT, SS XIA, QA DREW, PD SWOVELAND, PT AF DHIBJALBUT, SS XIA, QA DREW, PD SWOVELAND, PT TI DIFFERENTIAL UP-REGULATION OF HLA CLASS-I MOLECULES ON NEURONAL AND GLIAL-CELL LINES BY VIRUS-INFECTION CORRELATES WITH DIFFERENTIAL INDUCTION OF IFN-BETA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEX CLASS-I; EXPRESSION; ANTIGENS; RNA; INTERFERON; SEQUENCES; GENE AB Adult neurons normally lack the expression of MHC class I molecules, which has implications on virus clearance from the central nervous system. The author previously demonstrated that HLA class I up-regulation in measles virus (MV)-infected glial cells is primarily mediated by IFN-beta. In contrast, this study demonstrates that MV-infection of the neuronal cell lines IMR-32 and CHP-126 fails to up-regulate HLA class I expression, which was associated with an inability of MV to induce IFN-beta in the neuronal cell lines. However, treatment with IFN-beta or coculture of the IMR-32 neuronal cell line with MV-infected glioma cells resulted in the up-regulation of HLA class on the former, which could be neutralized by anti-IFN-beta Ab. The inability of MV to up-regulate HLA class expression on the neuronal cell line IMR-32 was not virus specific because similar findings were observed with mumps virus or stimulation with the synthetic dsRNA polyinosinic polycytidylic acid (PIPC). Induction of IFN-beta gene expression by virus requires binding of NF-kappa B to the positive regulatory domain II element of the IFN-beta promoter. Our studies indicate that MV, TNF-alpha, or PIPC induces NF-kappa B (p50 and p65 subunits) binding to positive regulatory domain II in the glioma cell line. In contrast such activity was induced by TNF-alpha but not MV or PIPC in the neuronal cell line IMR-32. This indicated that HLA class I expression is differentially regulated in glial and neuronal cell lines in response to MV, which correlates with differential binding of NF-kappa B to the IFN-beta promoter and induction of IFN-beta gene expression. C1 UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. VET ADM MED CTR,BALTIMORE,MD 21201. FU NINDS NIH HHS [P 50 NS 20022-09A1] NR 31 TC 23 Z9 23 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 AUG 15 PY 1995 VL 155 IS 4 BP 2096 EP 2108 PG 13 WC Immunology SC Immunology GA RN464 UT WOS:A1995RN46400047 PM 7636259 ER PT J AU DEIBLER, GE BURLIN, TV STONE, AL AF DEIBLER, GE BURLIN, TV STONE, AL TI 3 ISOFORMS OF HUMAN MYELIN BASIC-PROTEIN - PURIFICATION AND STRUCTURE SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE HUMAN MYELIN BASIC PROTEIN ISOFORMS; PHOSPHORYLATION; PROTEIN CONFORMATION; BETA-STRUCTURE ID CIRCULAR-DICHROISM; BETA-TURNS; PHOSPHORYLATION; IDENTIFICATION; SEQUENCE; CLONING; FORMS AB Myelin basic protein (MBP) occurs in multiple forms. Three of these isoforms from human MBP (HMBP) have been highly purified. HMBP, component 1 (18.5 kDa HMBP-1), was purified by ion-exchange chromatography at pH 10.6 in 2 M urea. During this ion-exchange chromatography, a fraction (Fraction 3), which contained HMBP component 3 (monophosphorylated or deamidated 18.5 kDa) and 17.2 kDa HMBP, was collected and further purified by fast protein liquid chromatography, which separated 17.2 kDa HMBP and HMBP component 3. When the latter was subjected to limited thrombic digestion, all of HMBP component 3 not phosphorylated at theonine 98 was cleaved. This digestion mixture was separated on Sephadex, and yielded pure component 3, monophosphorylated at theonine 98 (HMBP 3pT98), for which phosphate analysis yielded approximately 1 mole P/mole protein, and NMR showed only one phosphorylation site present. Circular dichroism (CD) studies were carried out on dilute solutions of HMBP-1 (18.5 kDa), 17.2 kDa HMBP, and HMBP3pT98 (phosphorylated 18.5 kDa). The CD spectrum of HMBP-1 was similar to that reported for rabbit MBP-1 and bovine MBP-1, but the spectra of 17.2 kDa HMBP and HMBP 3pT98 were distinctly different from HMBP-1. When analyzed by best-fit computations, 17.2 kDa HMBP showed about a 9% increase of ordered structure, and a greater increase, about 12%, was estimated for HMBP3pT98, attributable to beta-structure and beta turn. (C) 1995 Wiley-Liss, Inc. C1 NICHHD,DEV MOLEC IMMUN LAB,BETHESDA,MD 20892. RP DEIBLER, GE (reprint author), NIMH,CEREBRAL METAB LAB,36 CONVENT DR MSC 4030,BETHESDA,MD 20892, USA. NR 35 TC 11 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 1995 VL 41 IS 6 BP 819 EP 827 DI 10.1002/jnr.490410612 PG 9 WC Neurosciences SC Neurosciences & Neurology GA RR965 UT WOS:A1995RR96500011 PM 7500383 ER PT J AU PORRA, JM WEISS, GH MASOLIVER, J AF PORRA, JM WEISS, GH MASOLIVER, J TI A DIFFUSION-MODEL INCORPORATING ANISOTROPIC PROPERTIES SO PHYSICA A LA English DT Article ID TELEGRAPHERS EQUATION; BOUNDARIES; SCATTERING; TIMES AB A mathematical model suggested by Orsingher, motivated by possible applicability to diffusion processes in which anisotropic scattering is significant, is reanalyzed. It is shown that the propagator for the full multi-dimensional model does not satisfy a telegrapher's equation, as suggested by Orsingher, but that the propagator for the projection of motion on any one of the axes does. This can be used to analyze the results of a class of optical scattering measurements. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP PORRA, JM (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,DIAGONAL 647,E-08028 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 17 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD AUG 15 PY 1995 VL 218 IS 1-2 BP 229 EP 236 DI 10.1016/0378-4371(95)00129-U PG 8 WC Physics, Multidisciplinary SC Physics GA RP744 UT WOS:A1995RP74400015 ER PT J AU KEEGAN, AD JOHNSTON, JA TORTOLANI, PJ MCREYNOLDS, LJ KINZER, C OSHEA, JJ PAUL, WE AF KEEGAN, AD JOHNSTON, JA TORTOLANI, PJ MCREYNOLDS, LJ KINZER, C OSHEA, JJ PAUL, WE TI SIMILARITIES AND DIFFERENCES IN SIGNAL-TRANSDUCTION BY INTERLEUKIN-4 AND INTERLEUKIN 13 - ANALYSIS OF JANUS KINASE ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR GAMMA-CHAIN; TYROSINE PHOSPHORYLATION; IL-2 RECEPTOR; IGE SYNTHESIS; COMPONENT; CELLS; LYMPHOKINE; PATHWAYS; IGG4 AB The cytokines interleukin (IL) 4 and IL-13 induce many of the same biological responses, including class switching to IgE and induction of major histocompatibility complex class II antigens and CD23 on human B cells. It has recently been shown that IL-4 induces the tyrosine phosphorylation of a 170-kDa protein, a substrate called 4PS, and of the Janus kinase (JAK) family members JAK1 and JAK3. Because IL-13 has many functional effects similar to those of IL-4, we compared the ability of IL-4 and IL-13 to activate these signaling molecules in the human multifactor-dependent cell line TF-1. In this report we demonstrate that both IL-4 and IL-13 induced the tyrosine phosphorylation of 4PS and JAK1. Interestingly, although IL-4 induced the tyrosine phosphorylation of JAK3, we did not detect JAK3 phosphorylation in response to IL-13. These data suggest that IL-4 and IL-13 signal in similar ways via the activation of JAK1 and 4PS. However, our data further indicate that there are significant differences because IL-13 does not activate JAK3. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. NR 39 TC 101 Z9 102 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 AUG 15 PY 1995 VL 92 IS 17 BP 7681 EP 7685 DI 10.1073/pnas.92.17.7681 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800017 PM 7544000 ER PT J AU KIM, IY STADTMAN, TC AF KIM, IY STADTMAN, TC TI SELENOPHOSPHATE SYNTHETASE - DETECTION IN EXTRACTS OF RAT-TISSUES BY IMMUNOBLOT ASSAY AND PARTIAL-PURIFICATION OF THE ENZYME FROM THE ARCHEAN METHANOCOCCUS-VANNIELII SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MAMMALIAN; SELENOPHOSPHATE; SYNTHETASE ID ESCHERICHIA-COLI; SELENOCYSTEINE SYNTHASE; SALMONELLA-TYPHIMURIUM; TRANSFER-RNAS; SELENIUM; SEQUENCE AB In Escherichia coli and Salmonella typhimurium it has been shown that selenophosphate serves as the selenium donor for the conversion of seryl-tRNA to selenocysteyl-tRNA and for the synthesis of 2-selenouridine, a modified nucleoside present in tRNAs. Although selenocysteyl-tRNA also is formed in eukaryotes and is used for the specific insertion of selenocysteine into proteins, the precise mechanism of its biosynthesis from seryl-tRNA in these systems is not known, Because selenophosphate is extremely oxygen labile and difficult to identify in biological systems, we used an immunological approach to detect the possible presence of selenophosphate synthetase in mammalian tissues. With antibodies elicited to E. coli selenophosphate synthetase the enzyme was detected in extracts of rat brain, liver, kidney, and lung by immunoblotting. Especially high levels were detected in Methanacoccus vannielii, a member of the domain Archeae, and the enzyme was partially purified from this source, It seems likely that the use of selenophosphate as a selenium donor is widespread in biological systems. C1 NHLBI,IR LB,BIOCHEM LAB,BETHESDA,MD 20892. NR 17 TC 42 Z9 43 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 AUG 15 PY 1995 VL 92 IS 17 BP 7710 EP 7713 DI 10.1073/pnas.92.17.7710 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800023 PM 7644481 ER PT J AU BUNNELL, BA MUUL, LM DONAHUE, RE BLAESE, RM MORGAN, RA AF BUNNELL, BA MUUL, LM DONAHUE, RE BLAESE, RM MORGAN, RA TI HIGH-EFFICIENCY RETROVIRAL-MEDIATED GENE-TRANSFER INTO HUMAN AND NONHUMAN PRIMATE PERIPHERAL-BLOOD LYMPHOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE THERAPY; RETROVIRAL VECTOR; ADENOSINE DEAMINASE ID APE LEUKEMIA-VIRUS; CELL-LINES; EXPRESSION; VEHICLES; THERAPY AB Peripheral blood lymphocytes (PBLs) are primary targets for gene therapy of inherited and acquired disorders of the immune system, We describe the development of an optimized transduction system that provides for high-efficiency retrovirus-mediated gene transfer into primary PBLs. This optimized transduction protocol combines centrifugation of the lymphocytes (1000 x g) at the inception of transduction with phosphate depletion, low-temperature incubation (32 degrees C), and the use of the packaging cell line PG13. Gene marking studies of human and primate PBLs using these optimized transduction conditions demonstrated that the transduction efficiency exceeded 50% of the total lymphocyte population. The optimized transduction efficiency of PBLs with amphotropic retroviral vectors was in excess of 25%, The transduction procedure does not alter phenotype, viability, or expansion of the transduced cells, Our data indicate that this optimized transduction system leads to high-efficiency gene transfer into primary human lymphocytes, which obviates the requirement for selection of transduced cells prior to gene-therapy procedures, Thus, large quantities of healthy retrovirally transduced lymphocytes containing a broad immunological repertoire can be generated for use in clinical protocols. Our results represent a significant improvement in the methodology for the transduction of lymphocytes for gene therapy. C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 17 TC 213 Z9 219 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 AUG 15 PY 1995 VL 92 IS 17 BP 7739 EP 7743 DI 10.1073/pnas.92.17.7739 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800029 PM 7644487 ER PT J AU PERNIS, A WITTHUHN, B KEEGAN, AD NELMS, K GARFEIN, E IHLE, JN PAUL, WE PIERCE, JH ROTHMAN, P AF PERNIS, A WITTHUHN, B KEEGAN, AD NELMS, K GARFEIN, E IHLE, JN PAUL, WE PIERCE, JH ROTHMAN, P TI INTERLEUKIN-4 SIGNALS THROUGH 2 RELATED PATHWAYS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYTOKINE; JANUS KINASES; SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION ID RECEPTOR GAMMA-CHAIN; FUNCTIONAL COMPONENT; HEMATOPOIETIC-CELLS; IL-4; ACTIVATION AB The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4 inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL 4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors. C1 COLUMBIA UNIV COLL PHYS & SURG, DEPT MED, NEW YORK, NY 10032 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT MICROBIOL, NEW YORK, NY 10032 USA. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [P30CA21765]; NHLBI NIH HHS [HL53749]; NIAID NIH HHS [AI33540-01] NR 28 TC 79 Z9 79 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1995 VL 92 IS 17 BP 7971 EP 7975 DI 10.1073/pnas.92.17.7971 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RP748 UT WOS:A1995RP74800076 PM 7544011 ER PT J AU PIEPER, U KAPADIA, G ZHU, PP PETERKOFSKY, A HERZBERG, O AF PIEPER, U KAPADIA, G ZHU, PP PETERKOFSKY, A HERZBERG, O TI STRUCTURAL EVIDENCE FOR THE EVOLUTIONARY DIVERGENCE OF MYCOPLASMA FROM GRAM-POSITIVE BACTERIA - THE HISTIDINE-CONTAINING PHOSPHOCARRIER PROTEIN SO STRUCTURE LA English DT Article DE HISTIDINE-CONTAINING PHOSPHOCARRIER PROTEIN (HPR); PHOSPHOENOLPYRUVATE, SUGAR PHOSPHOTRANSFERASE (PTS) ID SUGAR PHOSPHOTRANSFERASE SYSTEM; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; STAPHYLOCOCCUS-AUREUS; TERTIARY STRUCTURE; HPR; PHOSPHOENOLPYRUVATE; NMR; SITE; PHOSPHORYLATION AB Background: The three-dimensional structures of histidine-containing phosphocarrier protein (HPr), a member of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), have been determined from Gram-negative and Gram-positive bacteria. The structure of HPr reported here for Mycoplasma capricolum is the first protein structure to be determined for this class of organism. Comparative structural studies with the bacterial proteins highlight sequence-structure correlations relevant to proposals about the evolutionary origin of mycoplasmas. Results: The crystal structure of HPr from M. capricolum has been determined and refined at 1.8 Angstrom resolution, revealing the same overall fold as that of other HPrs of known structure. However, mycoplasma HPr resembles HPrs from Gram-positive bacteria more closely than those from Gram-negative bacteria. As in HPrs from Bacillus subtilis and Escherichia coli, the phosphoryl group carrier (His15) forms the N-terminal cap of a helix, but in contrast to the other crystal structures, the side chain of the adjacent Arg17 is conformationally disordered. A sulfate ion interacts with Ser46, a residue known to be phosphorylated in a regulatory manner. Conclusions: The greater degree of structural similarity of the M. capricolum HPr to HPrs from Gram-positive rather than Gram-negative bacteria is consistent with the proposal that mycoplasma evolved from Gram-positive bacteria. The proposal that no major conformational transition is required for phosphorylation oi the active-site histidine is reinforced by comparing the crystal structures with and without an anion in the active site. The conformational disorder of the Arg17 side chain suggests that its guanidinium group does not have to form specific interactions with other protein groups before phosphorylation at His15. The association of a sulfate ion with Ser46 serves as a model for HPr(Ser46 similar to P). As there is no evidence of a conformational change accompanying Ser46 phosphorylation, the inhibitory effect of this event may be attributable to altered surface electrostatics. C1 UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NHLBI,BIOCHIM GENET LAB,BETHESDA,MD 20892. RI Pieper, Ursula/E-4444-2010 NR 43 TC 18 Z9 19 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD AUG 15 PY 1995 VL 3 IS 8 BP 781 EP 790 DI 10.1016/S0969-2126(01)00213-1 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RP892 UT WOS:A1995RP89200006 PM 7582895 ER PT J AU HORNE, MK MERRYMAN, PK MAYO, DJ GRALNICK, HR CHANG, RC ALEXANDER, HR AF HORNE, MK MERRYMAN, PK MAYO, DJ GRALNICK, HR CHANG, RC ALEXANDER, HR TI REDUCTIONS IN TISSUE-PLASMINOGEN ACTIVATOR AND THROMBOMODULIN IN BLOOD DRAINING VEINS DAMAGED BY VENOUS ACCESS DEVICES SO THROMBOSIS RESEARCH LA English DT Article DE THROMBOMODULIN; TISSUE PLASMINOGEN ACTIVATOR ID PLASMA THROMBOMODULIN; CANCER-PATIENTS AB A frequent complication of venous access devices (VADs) is axillary-subclavian venous thrombosis. To study this problem we have compared blood drawn through VADs with peripheral blood samples in a group of oncology patients with venographically demonstrated venous damage (N = 14) and a group with normal venograms (N = 21). The samples were assayed for a battery of proteins believed to be involved in thrombogenesis. After approximately six weeks of catheterization the venographically abnormal patients had significantly less thrombomodulin (P = 0.0055) and significantly higher PAI:tPA (P 0.022) in catheter-drawn samples as compared with the venographically normal group. Although the data are inconclusive, it is hypothesized that these changes resulted from local endothelial injury. C1 NCI,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RP HORNE, MK (reprint author), NCI,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,RM 2C390,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD AUG 15 PY 1995 VL 79 IS 4 BP 369 EP 376 DI 10.1016/0049-3848(95)00125-B PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RL207 UT WOS:A1995RL20700004 PM 7482440 ER PT J AU DETERAWADLEIGH, SD YOON, SW BERRETTINI, WH GOLDIN, LR TURNER, G YOSHIKAWA, T ROLLINS, DY MUNIEC, D NURNBERGER, JI GERSHON, ES AF DETERAWADLEIGH, SD YOON, SW BERRETTINI, WH GOLDIN, LR TURNER, G YOSHIKAWA, T ROLLINS, DY MUNIEC, D NURNBERGER, JI GERSHON, ES TI ADRENOCORTICOTROPIN RECEPTOR MELANOCORTIN RECEPTOR-2 MAPS WITHIN A REPORTED SUSCEPTIBILITY REGION FOR BIPOLAR ILLNESS ON CHROMOSOME-18 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE PCR-SSCP; D18S53; LINKAGE ANALYSIS ID SEARCH; GENES; CLONING; HORMONE; GENOME; LOCUS AB We have examined the possible linkage of adrenocorticotropin receptor/melanocortin receptor-2 (ACTHR/MC-2) to a reported putative susceptibility locus for bipolar illness (BP) in 20 affected pedigrees. Initially, allelic variants of the gene were identified by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) and the gene was genetically mapped using both the Centre d'Etudes du Polymorphisme Humain (CEPH) pedigrees and the BP pedigrees used in this study, We found that the ACTHR/MC-2 gene maps between D18S53 and D18S66. These loci span a region of chromosome 18 which, in a previous study [Berrettini et al.: Proc Natl Acad Sci USA 91:5918-5921, 1994) revealed a putative predisposing locus to BP through nonparametric methods of linkage analysis, Linkage of ACTHR/MC-2 to BP was not demonstrable under parametric and nonparametric methods of analyses, although affected sib-pair (ASP) method revealed an increase in allele sharing among ill individuals, P=0.023. Since this receptor is within a potential linkage region, ACTHR/MC-2 could be considered a candidate gene for BP. (C) 1995 Wiley-Liss, Inc.* C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. INDIANA UNIV,MED CTR,INST PSYCHIAT RES,INDIANAPOLIS,IN. RP DETERAWADLEIGH, SD (reprint author), NIMH,CLIN NEUROGENET BRANCH,GENE MAPPING & EXPRESS UNIT,BLDG 10,RM 3N218,BETHESDA,MD 20892, USA. OI Nurnberger, John/0000-0002-7674-1767 FU NCRR NIH HHS [1P41 RR03655] NR 22 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 14 PY 1995 VL 60 IS 4 BP 317 EP 321 DI 10.1002/ajmg.1320600411 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA RN773 UT WOS:A1995RN77300010 PM 7485268 ER PT J AU BACON, CM TORTOLANI, PJ SHIMOSAKA, A REES, RC LONGO, DL OSHEA, JJ AF BACON, CM TORTOLANI, PJ SHIMOSAKA, A REES, RC LONGO, DL OSHEA, JJ TI THROMBOPOIETIN (TPO) INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF STAT5 AND STAT3 SO FEBS LETTERS LA English DT Article DE THROMBOPOIETIN; SIGNAL TRANSDUCTION; SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT); TYROSINE PHOSPHORYLATION ID GAMMA-INTERFERON; GENE; RECEPTOR; PROTEINS; PROMOTER AB The growth and differentiation of megakaryocytes are regulated by thrombopoietin (TPO), a recently characterized cytokine which exerts its effects via a member of the hematopoietin receptor superfamily, c-Mpl, Since many cytokines which bind hematopoietin receptors activate the STAT family of transcription factors, we investigated whether STAT proteins were activated by TPO, TPO induced the formation of a DNA-binding complex recognizing a known STAT-binding sequence, STAT5 was a major component of this DNA-binding complex, and STAT5 was tyrosine phosphorylated in response to TPO, Additionally, TPO-induced the tyrosine phosphorylation and DNA-binding activity of STAT3. Together with the recent demonstration of JAK2 activation in response to TPO, the data presented here define a rapid signaling pathway likely to be important in TPO-induced gene regulation. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. KIRIN BREWING LTD,TOKYO,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NR 32 TC 63 Z9 64 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 14 PY 1995 VL 370 IS 1-2 BP 63 EP 68 DI 10.1016/0014-5793(95)00796-C PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RP890 UT WOS:A1995RP89000014 PM 7544303 ER PT J AU PICKAR, D AF PICKAR, D TI PHARMACOTHERAPY OF SCHIZOPHRENIA SO LANCET LA English DT Letter RP PICKAR, D (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD AUG 12 PY 1995 VL 346 IS 8972 BP 450 EP 450 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RN656 UT WOS:A1995RN65600063 ER PT J AU WANGE, RL GUITIAN, R ISAKOV, N WATTS, JD AEBERSOLD, R SAMELSON, LE AF WANGE, RL GUITIAN, R ISAKOV, N WATTS, JD AEBERSOLD, R SAMELSON, LE TI ACTIVATING AND INHIBITORY MUTATIONS IN ADJACENT TYROSINES IN THE KINASE DOMAIN OF ZAP-70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID CELL ANTIGEN RECEPTOR; ZETA-CHAIN; PROTEIN; PHOSPHORYLATION; AUTOPHOSPHORYLATION; PP60C-SRC; SITES; REPLACEMENT; PERVANADATE; EXPRESSION AB ZAP-70 is a 70-kDa protein tyrosine kinase, expressed exclusively in T cells and NK cells, and plays a critical role in mediating T cell activation in response to T cell receptor engagement, The strong correlation between tyrosine phosphorylation of ZAP-70 and its acquisition of increased kinase activity suggests that it is positively regulated by tyrosine phosphorylation, Previously, we identified tyrosines 492 and 493 of ZAP-70 as being sites of in vivo phosphorylation in response to T cell receptor engagement, To determine the role of phosphorylation in regulating ZAP-70 activity, we mutated each of these tyrosines individually to phenylalanine, When expressed in COS cells, Y493F-mutated ZAP-70 demonstrated normal basal kinase activity, but, unlike wild type ZAP-70, could not be activated by tyrosine phosphorylation induced by incubation with pervanadate or by co-expression of constitutively activated Lck, This suggests that Tyr-493 phosphorylation is required for the tyrosine phosphorylation-induced activation of ZAP-70, The Y492F mutation resulted in 4-fold higher basal kinase activity, which could be stimulated further by tyrosine phosphorylation, These results reveal that critical tyrosine residues in the kinase domain of ZAP-70 are important in regulation of its catalytic activity. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA. NR 42 TC 170 Z9 170 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 AUG 11 PY 1995 VL 270 IS 32 BP 18730 EP 18733 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN954 UT WOS:A1995RN95400006 PM 7642520 ER PT J AU TSAO, DHH GRUSCHUS, JM WANG, LH NIRENBERG, M FERRETTI, JA AF TSAO, DHH GRUSCHUS, JM WANG, LH NIRENBERG, M FERRETTI, JA TI THE 3-DIMENSIONAL SOLUTION STRUCTURE OF THE NK-2 HOMEODOMAIN FROM DROSOPHILA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE NK-2 HOMEODOMAIN; NUCLEAR MAGNETIC RESONANCE; 3-DIMENSIONAL SOLUTION STRUCTURE; DROSOPHILA MELANOGASTER; HELIX-TURN-HELIX ID MAGNETIC-RESONANCE SPECTROSCOPY; ANTENNAPEDIA HOMEODOMAIN; PROTEIN STRUCTURES; H-1-NMR SPECTRA; NUCLEAR; NMR; PROTON AB We describe the NMR determination of the three-dimensional structure of a 77 amino acid residue protein, which consists of the 60 residue NK-2 homeodomain from Drosophila melanognster and adjacent amino acid residues. The NK-2 homeodomain protein is part of a 723 amino acid residue protein which is expressed early in embryonic development in part of the central nervous system. NK-2 was characterized using both a natural abundance and a uniformly N-15 enriched sample by two-dimensional and three-dimensional NMR experiments. The average root-mean-square deviation for 30 structures for residues 8 to 53 is 0.40 Angstrom for the backbone heavy-atoms and 0.72 Angstrom for the backbone and side-chain heavy-atoms. These structures were obtained from 986 NOE-derived upper and lower bound restraints. The three-dimensional structure contains three helices which consist of homeodomain amino acid residues 10 to 22, 28 to 38 and 42 to 52, as well as a turn between helix II and III, characteristic of homeodomains. Residues 53 to 60 of the DNA recognition helix are not fully ordered in the absence of DNA. In the free state this segment adopts a flexible but helix-like structure between residues 53 and 56 and is disordered from residues 57 to 60 although, as shown previously, the helix elongates by eight residues upon binding to DNA. The role of variable residues 52, 54 and 56 in determining the structure and flexibility of the recognition helix, as well as the stability of the NK-2 homeodomain as manifested by its thermal denaturation, are discussed. (C) 1995 Academic Press Limited C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 28 TC 58 Z9 59 U1 1 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 11 PY 1995 VL 251 IS 2 BP 297 EP 307 DI 10.1006/jmbi.1995.0435 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN632 UT WOS:A1995RN63200011 PM 7643404 ER PT J AU MAZUMDER, A POMMIER, Y AF MAZUMDER, A POMMIER, Y TI PROCESSING OF DEOXYURIDINE MISMATCHES AND ABASIC SITES BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID URACIL-DNA GLYCOSYLASE; HIV-1 REVERSE-TRANSCRIPTASE; PROTEIN INVITRO; BASE-PAIRS; EXTENSION; KINETICS; SEQUENCE; NMR; INTERFERENCE; REPLICATION AB We have examined the activities of HIV-1 integrase on substrates containing mismatches, composed of deoxyuridine at different positions in either the processed or nonprocessed strand of viral DNA, within and near the conserved CA dinucleotide of the U5 end of the HIV-1 LTR. Substitution in the processed strand of either the C or A of the CA dinucleotide or of the G 5' to the CA reduced strand transfer six-, three- and seven-fold respectively. 3'-processing was also reduced by substitution at the GC but not at the A. Substitution in the nonprocessed strand of the G nucleotide at the processing site abolished strand transfer while substitution of the T had no effect. DNA binding of HIV-1 integrase was not affected by deoxyuridine substitutions. Deoxyuridine substitution outside the trinucleotide remained compatible with enzyme activity. Enzymatically generated abasic sites were created at each mismatch to determine the effect of a missing base on integrase activity. Consistent with the deoxyuridine mismatch observations, 3'-processing and strand transfer were abolished when the abasic site was substituted for either of the nucleotides of the GCA trinucleotide. Integrase was, however, able to tolerate mismatches within this trinucleotide during the disintegration reaction. Taken together, these results suggest that base-mismatched or base-deleted substrates, which can be created by the proofreading-deficient HIV-1 RT, can be tolerated by HIV-1 integrase when located outside of the GCA trinucleotide at the U5 end of the LTR. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 42 TC 25 Z9 26 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 AUG 11 PY 1995 VL 23 IS 15 BP 2865 EP 2871 DI 10.1093/nar/23.15.2865 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100010 PM 7659508 ER PT J AU HAWKINS, ME PFLEIDERER, W MAZUMDER, A POMMIER, YG FALLS, FM AF HAWKINS, ME PFLEIDERER, W MAZUMDER, A POMMIER, YG FALLS, FM TI INCORPORATION OF A FLUORESCENT GUANOSINE ANALOG INTO OLIGONUCLEOTIDES AND ITS APPLICATION TO A REAL-TIME ASSAY FOR THE HIV-1 INTEGRASE 3'-PROCESSING REACTION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS INTEGRASE; = PTERIDINE-2,4(1H,3H)-DIONE CHROMOPHORE; RETROVIRAL INTEGRATION; BATHOPHENANTHROLINE-RUTHENIUM(II) COMPLEXES; ENERGY-TRANSFER; VIRAL-DNA; PROTEIN; INVITRO; HYBRIDIZATION; SUBSTRATE AB We have synthesized a highly fluorescent (quantum yield 0.88) guanosine analog, (3-methyl-8-(2-deoxy-beta-D-ribofuranosyl) isoxanthopterin (3-MI) in a dimethoxytrityl, phosphoramidite protected form, which can be site-specifically inserted into oligonucleotides through a 3',5'-phosphodiester linkage using an automated DNA synthesizer Fluorescence is partially quenched within an oligonucleotide and the degree of quench is a function of the fluorophore's proximity to purines and its position in the oligonucleotide. As an example of the potential utility of this class of fluorophores, we developed a continuous assay for HIV-1 integrase 3'-processing reaction by incorporating 3-MI at the cleavage site in a double-stranded oligonucleotide identical to the U5 terminal sequence of the HIV genome, Integrase cleaves the 3'-terminal dinucleotide containing the fluorophore, resulting in an increase in fluorescence which can be monitored on a spectrofluorometer. Substitution of the fluorophore for guanosine at the cleavage site does not inhibit integrase activity. This assay is specific for the 3'-processing reaction. The change in fluorescence intensity is linear over time and proportional to the rate of the reaction. This assay demonstrates the potential utility of this new class of fluorophore for continuous monitoring of protein/DNA interactions. C1 UNIV KONSTANZ, FAK CHEM, D-78464 CONSTANCE, GERMANY. NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA. RP HAWKINS, ME (reprint author), NCI, PEDIAT BRANCH, BLDG 10-13N240, 10 CTR DR, MSC 1928, BETHESDA, MD 20892 USA. NR 40 TC 81 Z9 82 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 11 PY 1995 VL 23 IS 15 BP 2872 EP 2880 DI 10.1093/nar/23.15.2872 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100011 PM 7659509 ER PT J AU BURGIN, AB HUIZENGA, BN NASH, HA AF BURGIN, AB HUIZENGA, BN NASH, HA TI A NOVEL SUICIDE SUBSTRATE FOR DNA TOPOISOMERASES AND SITE-SPECIFIC RECOMBINASES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LAMBDA INTEGRATIVE RECOMBINATION; BACTERIOPHAGE-LAMBDA; STRAND TRANSFER; EUKARYOTIC TOPOISOMERASE; PROTEIN; CLEAVAGE; PURIFICATION; MECHANISM; INT AB DNA topoisomerases and DNA site-specific recombinases are biologically important enzymes involved in a diverse set of cellular processes. We show that replacement of a phosphodiester linkage by a 5'-bridging phosphorothioate linkage creates an efficient suicide substrate for calf thymus topoisomerase I and lambda integrase protein (Int). Although the bridging phosphorothioate linkage is cleaved by these enzymes, the 5'-sulfhydryl which is generated is not competent for subsequent ligation reactions. We use the irreversibility of Int-promoted cleavage to explore conditions and factors that contribute to various steps of lambda integrative recombination, The phosphorothioate substrates offer advantages over conventional suicide substrates, may be potent tools for inhibition of the relevant cellular enzymes and represent a unique tool for the study of many other phosphoryl transfer reactions. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 36 TC 64 Z9 64 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 AUG 11 PY 1995 VL 23 IS 15 BP 2973 EP 2979 DI 10.1093/nar/23.15.2973 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100025 PM 7659520 ER PT J AU ENGERT, JC SERVAES, S SUTRAVE, P HUGHES, SH ROSENTHAL, N AF ENGERT, JC SERVAES, S SUTRAVE, P HUGHES, SH ROSENTHAL, N TI ACTIVATION OF A MUSCLE-SPECIFIC ENHANCER BY THE SKI PROTOONCOGENE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LIGHT CHAIN ENHANCER; CREATINE-KINASE GENE; REGULATORY FACTORS; SKELETAL-MUSCLE; UPSTREAM ELEMENTS; TRANSGENIC MICE; EXPRESSION; MYOGENIN; CELLS; DIFFERENTIATION AB In transgenic mice, muscle-specific expression of the c-ski oncogene induces hypertrophy exclusively in a subset of fast muscle fibers, Here we report that regulatory elements from two genes expressed in fast fibers, myosin light chain 1/3 (MLC) and muscle creatine kinase (MCK), were activated when co-transfected with c-ski expression vectors in myoblasts, The expression from the MLC enhancer was reduced when the c-ski oncogene was cotransfected with MyoD into NIH3T3 fibroblasts, Activation of the MLC enhancer by Ski also occurred in vivo, since bigenic progeny generated by mating MLC-CAT and MSV-ski transgenic mice displayed higher CAT activity in their muscles than did the MLC-CAT parental line, Identification of gene targets for the fiber-specific action of the c-ski gene product provides a molecular model that could be used for the further dissection of Ski-induced hypertrophy, both in tissue culture and in vivo. C1 MASSACHUSETTS GEN HOSP E,CARDIOVASC RES CTR,BOSTON,MA 02129. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NIA NIH HHS [R01AG12316]; NIAMS NIH HHS [R01AR41926] NR 40 TC 34 Z9 34 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 AUG 11 PY 1995 VL 23 IS 15 BP 2988 EP 2994 DI 10.1093/nar/23.15.2988 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100027 PM 7659522 ER PT J AU CHIN, K ODA, N SHEN, K NOGUCHI, CT AF CHIN, K ODA, N SHEN, K NOGUCHI, CT TI REGULATION OF TRANSCRIPTION OF THE HUMAN ERYTHROPOIETIN RECEPTOR GENE BY PROTEINS BINDING TO GATA-1 AND SP1 MOTIFS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LEUKEMIA-CELL-LINE; ERYTHROID-CELLS; EXPRESSION; MODULATION; PROMOTER; DIFFERENTIATION; ORGANIZATION; ACTIVATION; CLONING; FAMILY AB Erythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors. We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene. In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1. The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression. The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation. Protein-DNA binding studies suggested that Sp1 acid two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif. By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562. Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells. These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone. Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression. C1 NIDDKD,BIOL CHEM LAB,BETHESDA,MD 20892. NR 38 TC 54 Z9 55 U1 0 U2 1 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 AUG 11 PY 1995 VL 23 IS 15 BP 3041 EP 3049 DI 10.1093/nar/23.15.3041 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100034 PM 7659529 ER PT J AU LORIMER, IAJ PASTAN, I AF LORIMER, IAJ PASTAN, I TI RANDOM RECOMBINATION OF ANTIBODY SINGLE-CHAIN FV SEQUENCES AFTER FRAGMENTATION WITH DNASEI IN THE PRESENCE OF MN2+ SO NUCLEIC ACIDS RESEARCH LA English DT Article C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 12 TC 46 Z9 49 U1 1 U2 1 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 AUG 11 PY 1995 VL 23 IS 15 BP 3067 EP 3068 DI 10.1093/nar/23.15.3067 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR361 UT WOS:A1995RR36100038 PM 7659531 ER PT J AU PINN, VW AF PINN, VW TI EQUITY IN BIOMEDICAL-RESEARCH SO SCIENCE LA English DT Editorial Material RP PINN, VW (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 1 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 11 PY 1995 VL 269 IS 5225 BP 739 EP 739 DI 10.1126/science.7638579 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RN650 UT WOS:A1995RN65000001 PM 7638579 ER PT J AU KEEN, TJ INGLEHEARN, CF GREEN, ED CUNNINGHAM, AF PATEL, RJ PEACOCK, RE GERKEN, S WHITE, R WESSENBACH, J BHATTACHARYA, SS AF KEEN, TJ INGLEHEARN, CF GREEN, ED CUNNINGHAM, AF PATEL, RJ PEACOCK, RE GERKEN, S WHITE, R WESSENBACH, J BHATTACHARYA, SS TI YAC CONTIG SPANNING THE DOMINANT RETINITIS-PIGMENTOSA LOCUS (RP9) ON CHROMOSOME 7P SO GENOMICS LA English DT Article ID GENOME AB The dominant retinitis pigmentosa locus RP9 has previously been localized to 7p13-p15, in the interval D7S526-D7S484. We now report refinement of the locus to the interval D7S795-D7S484 and a YAC contig of approximately 4.8 Mb spanning this region and extending both distally and proximally from it. The contig was constructed by STS content mapping and physically orders 29 STSs in 28 YAC clones. The order of polymorphic markers in the contig is consistent with a genetic map that has been assembled using haplotype data from the CEPH pedigrees. This contig will provide a primary resource for the construction of a transcriptional map of this region and for the identification of the defective gene causing this form of adRP. (C) 1995 Academic Press, Inc. C1 INST OPHTHALMOL,DEPT MOLEC GENET,LONDON EC1V 9EL,ENGLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. GENETHON,CNRS,URA 1922,EVRY,FRANCE. FU Wellcome Trust NR 26 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 10 PY 1995 VL 28 IS 3 BP 383 EP 388 DI 10.1006/geno.1995.1165 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ989 UT WOS:A1995RQ98900003 PM 7490071 ER PT J AU HULSEBOS, TJM CEROSALETTI, KM FOURNIER, REK SINKE, RJ ROCCHI, M MARZELLA, R JENKINS, NA GILBERT, DJ COPELAND, NG AF HULSEBOS, TJM CEROSALETTI, KM FOURNIER, REK SINKE, RJ ROCCHI, M MARZELLA, R JENKINS, NA GILBERT, DJ COPELAND, NG TI IDENTIFICATION OF THE HUMAN BETA-A2 CRYSTALLIN GENE (CRYBA2) - LOCALIZATION OF THE GENE ON HUMAN-CHROMOSOME-2 AND OF THE HOMOLOGOUS GENE ON MOUSE CHROMOSOME-1 SO GENOMICS LA English DT Article ID GAMMA; EXPRESSION; ASSIGNMENT; SEQUENCES; MUTATION; REGION; FAMILY; LOCUS AB By using primers synthesized on the basis of the bovine beta A2 crystallin gene sequence, we amplified exons 5 and 6 of the human gene (CRYBA2). CRYBA2 was assigned to human chromosome 2 by concordance analysis in human x rodent somatic cell hybrids using the amplified PCR products as probe. Regional localization to 2q34-q36 was established by hybridizing the CRYBA2 probe to microcell and radiation hybrids containing defined fragments of chromosome 2 as the only human contribution. The CRYBA2 probe was also used to localize, by interspecific backcross mapping, the mouse gene (Cryba2) to the central portion of chromosome 1 in a region of known human chromosome 2 homology. Finally, we demonstrate that in both species the beta A2 crystallin gene is linked but separable from the gamma A crystallin gene. The beta A2 crystallin gene is a candidate gene for human and mouse hereditary cataract. (C) 1995 Academic Press, Inc. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV NIJMEGEN HOSP,DEPT HUMAN GENET,6500 HB NIJMEGEN,NETHERLANDS. UNIV BARI,IST GENET,BARI,ITALY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP HULSEBOS, TJM (reprint author), UNIV AMSTERDAM,ACAD MED CTR,FAC MED,INST HUMAN GENET,MEIBERGDREEF 9,1105 AZ AMSTERDAM,NETHERLANDS. RI Sinke, Richard/A-1462-2009; Rocchi, Mariano/B-8451-2011 FU NCI NIH HHS [N01-CO-46000]; NIGMS NIH HHS [GM26449] NR 32 TC 11 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 10 PY 1995 VL 28 IS 3 BP 543 EP 548 DI 10.1006/geno.1995.1186 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ989 UT WOS:A1995RQ98900024 PM 7490092 ER PT J AU MARKER, PC KING, JA COPELAND, NG JENKINS, NA KINGSLEY, DM AF MARKER, PC KING, JA COPELAND, NG JENKINS, NA KINGSLEY, DM TI CHROMOSOMAL LOCALIZATION, EMBRYONIC EXPRESSION, AND IMPRINTING TESTS FOR BMP7 ON DISTAL MOUSE CHROMOSOME-2 SO GENOMICS LA English DT Note ID GENETIC-LINKAGE MAP; OSTEOGENIC PROTEIN; BETA SUPERFAMILY; BONE-FORMATION; RNA; MORPHOGENESIS; PATTERNS; SUGGEST; INVITRO; FAMILY AB Murine Bmp7 has been assigned to distal Chromosome 2 by interspecific backcross mapping. The map location suggests close linkage to classical mouse mutations and places Bmp7 within a chromosome region thought to contain one or more unidentified imprinted genes. A direct test suggests that Bmp7 is not imprinted. An examination of embryonic RNA expression patterns shows that Bmp7 is expressed in a variety of skeletal and nonskeletal tissues. Both embryonic expression patterns and the human chromosomal sublocalization inferred from its mouse location make Bmp7 a candidate for the gene affected in some patients with Holt-Gram syndrome. (C) 1995 Academic Press, Inc. C1 STANFORD UNIV,SCH MED,BECKMAN CTR,DEPT DEV BIOL,STANFORD,CA 94305. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01CO46,000] NR 29 TC 11 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 10 PY 1995 VL 28 IS 3 BP 576 EP 580 DI 10.1006/geno.1995.1192 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ989 UT WOS:A1995RQ98900030 PM 7490098 ER PT J AU OHSHIMA, J NAGLE, JW PANT, HC JOSHI, JB KOZAK, CA BRADY, RO KULKARNI, AB AF OHSHIMA, J NAGLE, JW PANT, HC JOSHI, JB KOZAK, CA BRADY, RO KULKARNI, AB TI MOLECULAR-CLONING AND CHROMOSOMAL MAPPING OF THE MOUSE CYCLIN-DEPENDENT KINASE-5 GENE SO GENOMICS LA English DT Note ID DIRECTED PROTEIN-KINASE; CDC2-LIKE KINASE; ELEMENT; SITES AB Cyclin-dependent kinase 5 (Cdk5) is predominantly expressed in neurons. In vitro, Cdk5 purified from the nervous tissue phosphorylates both high-molecular-weight neurofilament and microtubule-associated tau. The mouse gene encoding Cdk5 (Cdk5) was found to be 5 kb in length and divided into 12 exons. All of the exon-intron junctions matched the expected consensus sequence with the exception of the splice junction for intron 9, which has AT and AC dinucleotides instead of the usual GT and AC; bordering sequence. In the 5'-flanking region of mouse Cdk5, several putative promoter elements were present, including AP1, Sp1, PuF, and TATA motifs. A metal regulatory element was also identified at position -207 to -201. Nucleotide sequence analysis of mouse Cdk5 showed high identity to the homologues of other vertebrate species, indicating that this kinase is highly conserved during evolution. Mouse Cdk5 was mapped to the centromeric region of mouse chromosome 5. (C) 1995 Academic Press, Inc. C1 NINCDS,MOUSE GENET & HUMAN DIS MODELS UNIT,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROGENET SECT,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20037. VET AFFAIRS MED CTR,MOLEC BIOL LAB,WASHINGTON,DC 20037. NR 20 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 10 PY 1995 VL 28 IS 3 BP 585 EP 588 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ989 UT WOS:A1995RQ98900032 ER PT J AU CHIN, HM KWON, OJ JUNG, HH KIM, DS KOZAK, CA AF CHIN, HM KWON, OJ JUNG, HH KIM, DS KOZAK, CA TI GENETIC-MAPPING OF THE MOUSE GENES ENCODING THE VOLTAGE-SENSITIVE CALCIUM-CHANNEL SUBUNITS SO GENOMICS LA English DT Note ID ALPHA-1 SUBUNIT; FAMILY; MAPS AB The genes encoding the alpha(1) and beta subunits of voltage-sensitive calcium channel were mapped in the mouse by analysis of the progeny of two multilocus crosses. The alpha(1), beta(2), and beta(4) subunit genes, termed Cchna1, Cchb2, and Cchb4, are located at different sites on proximal Chr 2, while the beta(3) subunit gene Cchb3 maps to Chr 15 near Wnt1. These results together with previous mapping data indicate that the calcium channel genes are dispersed in the mouse genome, unlike the sodium channel genes, which are clustered. (C) Academic Press, Inc. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP CHIN, HM (reprint author), NINCDS,NEUROCHEM LAB,BLDG 36,RM 4D20,BETHESDA,MD 20892, USA. NR 20 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 10 PY 1995 VL 28 IS 3 BP 592 EP 595 DI 10.1006/geno.1995.1196 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ989 UT WOS:A1995RQ98900034 PM 7490102 ER PT J AU GIGUERE, V BEATTY, B SQUIRE, J COPELAND, NG JENKINS, NA AF GIGUERE, V BEATTY, B SQUIRE, J COPELAND, NG JENKINS, NA TI THE ORPHAN NUCLEAR RECEPTOR ROR-ALPHA (RORA) MAPS TO A CONSERVED REGION OF HOMOLOGY ON HUMAN-CHROMOSOME 15Q21-Q22 AND MOUSE CHROMOSOME-9 SO GENOMICS LA English DT Note ID GENETIC-LINKAGE MAP; INSITU HYBRIDIZATION; SUPERFAMILY AB ROR alpha is a novel member of the steroid/thyroid/retinoid receptor superfamily with unique DNA-binding properties. We have mapped the RORA gene by fluorescence in situ hybridization to human chromosome 15q21-q22. To map the mouse Rora gene, a partial mouse cDNA clone was isolated from brain. Using interspecific backcross analysis, we have mapped the Rora gene 60 mouse chromosome 9. This places the human RORA gene in the proximity of the PML gene, which is involved in a reciprocal chromosomal translocation t(15:17) with the RARA gene in patients with acute promyelocytic leukemia. (C) 1995 Academic Press, Inc. C1 MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT ONCOL,MONTREAL,PQ H3A 1A1,CANADA. HOSP SICK CHILDREN,CGAT FISH MAPPING RESOURCE CTR,TORONTO,ON M5G 1X8,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP GIGUERE, V (reprint author), MCGILL UNIV,ROYAL VICTORIA HOSP,MOLEC ONCOL GRP,687 PINE AVE W,MONTREAL,PQ H3A 1A1,CANADA. OI Giguere, Vincent/0000-0001-9567-3694; Squire, Jeremy/0000-0002-9863-468X FU NCI NIH HHS [N01-CO-46000] NR 13 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 10 PY 1995 VL 28 IS 3 BP 596 EP 598 DI 10.1006/geno.1995.1197 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ989 UT WOS:A1995RQ98900035 PM 7490103 ER PT J AU WALSTON, J SILVER, K BOGARDUS, C KNOWLER, WC CELI, FS AUSTIN, S MANNING, B STROSBERG, AD STERN, MP RABEN, N SORKIN, JD ROTH, J SHULDINER, AR AF WALSTON, J SILVER, K BOGARDUS, C KNOWLER, WC CELI, FS AUSTIN, S MANNING, B STROSBERG, AD STERN, MP RABEN, N SORKIN, JD ROTH, J SHULDINER, AR TI TIME OF ONSET OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND GENETIC-VARIATION IN THE BETA(3)-ADRENERGIC-RECEPTOR GENE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BROWN ADIPOSE-TISSUE; BETA-3-ADRENERGIC RECEPTOR; GLUCOSE-TOLERANCE; METABOLIC-RATE; OBESITY; THERMOGENESIS; MUTATIONS; CHAIN; RISK AB Background. The beta(3)-adrenergic receptor is expressed in visceral adipose tissue and is thought to contribute to the regulation of the resting metabolic rate and lipolysis. Methods. To investigate whether mutations in the gene for the beta(3)-adrenergic receptor predispose patients to obesity and non-insulin-dependent diabetes mellitus (NIDDM), we studied this gene in 10 Pima Indians by analysis of single-stranded conformational polymorphisms and dideoxy sequence analysis. Association studies were performed in 642 Pima subjects (390 with NIDDM and 252 without NIDDM). Results. A missense mutation was identified in the gene for the beta(3)-adrenergic receptor that results in the replacement of tryptophan by arginine (Trp64Arg) in the first intracellular loop of the receptor. This mutation was detected with allelic frequencies of 0.31 in Pima Indians, 0.13 in 62 Mexican Americans, 0.12 in 49 blacks, and 0.08 in 48 whites in the United States. Among Pimas, the frequency of the Trp64Arg mutation was similar in nondiabetic and diabetic subjects. However, in subjects homozygous for the mutation the mean (+/-SD) age at the onset of NIDDM was significantly lower (36+/-10 years) than in Trp64Arg heterozygotes (40+/-10 years) or normal homozygotes (41 +/- 11 years; P = 0.02). Furthermore, subjects with the mutation tended to have a lower adjusted resting metabolic rate (P = 0.14 by analysis of covariance). Conclusions. Pima subjects homozygous for the Trp64Arg beta(3)-adrenergic-receptor mutation have an earlier onset of NIDDM and tend to have a lower resting metabolic rate. This mutation may accelerate the onset of NIDDM by altering the balance of energy metabolism invisceral adipose tissue. C1 JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DIV ENDOCRINOL & METAB,BALTIMORE,MD. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NIDDKD,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ 85016. NIA,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. INST COCHIN GENET MOLEC,IMMUNOPHARMACOL MOLEC LAB,F-75014 PARIS,FRANCE. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. FU NIA NIH HHS [5T32AG00120] NR 35 TC 519 Z9 546 U1 0 U2 6 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 AUG 10 PY 1995 VL 333 IS 6 BP 343 EP 347 DI 10.1056/NEJM199508103330603 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RN082 UT WOS:A1995RN08200003 PM 7609750 ER PT J AU CHOW, WH FINKLE, WD MCLAUGHLIN, JK FRANKL, H ZIEL, HK FRAUMENI, JF AF CHOW, WH FINKLE, WD MCLAUGHLIN, JK FRANKL, H ZIEL, HK FRAUMENI, JF TI THE RELATION OF GASTROESOPHAGEAL REFLUX DISEASE AND ITS TREATMENT TO ADENOCARCINOMAS OF THE ESOPHAGUS AND GASTRIC CARDIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BARRETTS-ESOPHAGUS; CIMETIDINE; CANCER AB Objective.-To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC). Design.-A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status. Setting.-A large prepaid health plan. Subjects.-Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership. Main Outcome Measures.-Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H-2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]). Results.-Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H-2 antagonists, the risk was reduced to 1.5 (95% CI, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend=.08). Conclusions.-This study provides reassuring findings that use of H-2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC. C1 INT EPIDEMIOL INST,ROCKVILLE,MD 20850. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. SO CALIF PERMANENTE MED GRP,DEPT MED,LOS ANGELES,CA 90027. SO CALIF PERMANENTE MED GRP,DEPT OBSTET & GYNECOL,LOS ANGELES,CA 90027. FU NCI NIH HHS [N01 CP 95680] NR 25 TC 263 Z9 267 U1 2 U2 7 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 AUG 9 PY 1995 VL 274 IS 6 BP 474 EP 477 DI 10.1001/jama.274.6.474 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA RM699 UT WOS:A1995RM69900027 PM 7629956 ER PT J AU LODI, PJ ERNST, JA KUSZEWSKI, J HICKMAN, AB ENGELMAN, A CRAIGIE, R CLORE, GM GRONENBORN, AM AF LODI, PJ ERNST, JA KUSZEWSKI, J HICKMAN, AB ENGELMAN, A CRAIGIE, R CLORE, GM GRONENBORN, AM TI SOLUTION STRUCTURE OF THE DNA-BINDING DOMAIN OF HIV-1 INTEGRASE SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; NMR-SPECTROSCOPY; ESCHERICHIA-COLI; PROTEIN; IDENTIFICATION; RESOLUTION; DYNAMICS; H-1-NMR; ENERGY; TYPE-1 AB The solution structure of the DNA binding domain of HIV-1 integrase (residues 220-270) has been determined by multidimensional NMR spectroscopy. The protein is a dimer in solution, and each subunit is composed of a five-stranded beta-barrel with a topology very similar to that of the SH3 domain. The dimer is formed by a stacked beta-interface comprising strands 2, 3, and 4, with the two triple-stranded antiparallel beta-sheets, one from each subunit, oriented antiparallel to each other. One surface of the dimer, bounded by the loop between strands beta 1 and beta 2, forms a saddle-shaped groove with dimensions of approximately 24 x 23 x 12 Angstrom in cross section. Lys264, which has been shown from mutational data to be involved in DNA binding, protrudes from this surface, implicating the saddle-shaped groove as the potential DNA binding site. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 48 TC 230 Z9 235 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 8 PY 1995 VL 34 IS 31 BP 9826 EP 9833 DI 10.1021/bi00031a002 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN732 UT WOS:A1995RN73200002 PM 7632683 ER PT J AU SAIKAWA, Y PRICE, K HANCE, KW CHEN, TY ELWOOD, PC AF SAIKAWA, Y PRICE, K HANCE, KW CHEN, TY ELWOOD, PC TI STRUCTURAL AND FUNCTIONAL-ANALYSIS OF THE HUMAN KB CELL FOLATE RECEPTOR GENE P4 PROMOTER - COOPERATION OF 3 CLUSTERED SP1-BINDING SITES WITH INITIATOR REGION FOR BASAL PROMOTER ACTIVITY SO BIOCHEMISTRY LA English DT Article ID RNA POLYMERASE-II; TRANSCRIPTION FACTOR SP1; BOX-BINDING-PROTEINS; LESS PROMOTER; SEQUENCE; CLONING; DNA; EXPRESSION; COMPLEX; ELEMENT AB The human folate receptors (hFRs) are important in the cellular accumulation of folates and antifolates. We described the structure of the human KB cell FR (hFR-KB) gene and identified two discrete promoter regions (P1 and P4) upstream from exons 1 and 4, respectively (Elwood et al., 1993). To further understand the molecular basis of hFR expression, we have now analyzed the basal transcription of the P4 promoter localized upstream of a major transcription start site. The sequence upstream from exon 4 contains several potential transcriptional factor-binding sites and a consensus initiator region sequence at the transcription start site but does not contain canonical TATA or CAAT boxes. While deletion of a 5' flanking sequence from nt - 1023 to nt - 605 of P4 promoter region decreases the luciferase reporter gene expression in KB cells to 54 - 70% of control construct, the removal of the sequence between nt - 292 and nt - 46 markedly decreases the activity to 3%. DNase I footprints and competitive mobility shift and supershift mobility assays indicate that Spl or Spl-related nuclear protein(s) bind to three clustered GC-rich regions within the sequence between nt - 292 and nt - 46 of the hFR-KB P4 promoter. Both in vitro and in vivo analyses of the expression of promoter constructs containing site-specific mutation(s) of these three Spl-binding sites and initiator sequence demonstrate that each of three Spl sites and the initiator sequence are required for optimum promoter activity and that they interact cooperatively in this P4 promoter of the hFR-KB gene. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 49 TC 43 Z9 43 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 8 PY 1995 VL 34 IS 31 BP 9951 EP 9961 DI 10.1021/bi00031a018 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN732 UT WOS:A1995RN73200018 PM 7632694 ER PT J AU GIEDD, JN KOZUCH, P KAYSEN, D VAITUZIS, AC HAMBURGER, SD BARTKO, JJ RAPOPORT, JL AF GIEDD, JN KOZUCH, P KAYSEN, D VAITUZIS, AC HAMBURGER, SD BARTKO, JJ RAPOPORT, JL TI RELIABILITY OF CEREBRAL MEASURES IN REPEATED EXAMINATIONS WITH MAGNETIC-RESONANCE-IMAGING SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE BRAIN, MORPHOLOGY; MRI RESCAN RELIABILITY; CAUDATE NUCLEUS; CEREBRUM; CORPUS CALLOSUM ID MRI; BRAIN AB This study examined the reliability of quantitative measures of cerebral magnetic resonance images (MRI) in repeated scans. Ten subjects were scanned twice, at 2- to 4-week intervals. Volumetric data from 14 regions of the cerebrum, the caudate nucleus, and the lateral ventricles and area measures of the corpus callosum were acquired. Intrarater and scan-rescan reliabilities, including the relative percent error from each of these two sources, were determined for each structure, Intraclass correlations ranged from 0.88 for the head of the caudate nucleus to 0.99 for the ventricular volume, Quantitative cerebral MRI measures of these structures are stable over time intervals of 2-4 weeks. C1 NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. RP GIEDD, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,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; kozuch, patricia/0000-0002-7465-9671 NR 8 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 8 PY 1995 VL 61 IS 2 BP 113 EP 119 DI 10.1016/0925-4927(95)02593-M PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RQ596 UT WOS:A1995RQ59600005 PM 7480388 ER PT J AU ARANGO, V UNDERWOOD, MD GUBBI, AV MANN, JJ AF ARANGO, V UNDERWOOD, MD GUBBI, AV MANN, JJ TI LOCALIZED ALTERATIONS IN PRESYNAPTIC AND POSTSYNAPTIC SEROTONIN BINDING-SITES IN THE VENTROLATERAL PREFRONTAL CORTEX OF SUICIDE VICTIMS SO BRAIN RESEARCH LA English DT Article DE QUANTITATIVE RECEPTOR AUTORADIOGRAPHY; [H-3] 8-OH-DPAT; [3H]CYANOIMIPRAMINE; 5-HT1A RECEPTOR; SEROTONIN TRANSPORTER; HPLC; 5-HIAA ID TRITIATED IMIPRAMINE BINDING; ADRENERGIC-RECEPTOR BINDING; H-3 PAROXETINE BINDING; RAT-BRAIN; MONOAMINE METABOLITES; FRONTAL-CORTEX; CEREBROSPINAL-FLUID; POST-MORTEM; QUANTITATIVE AUTORADIOGRAPHY; HEMISPHERIC-ASYMMETRY AB Altered serotonin indices have been reported in the brain of suicide victims. We sought to localize the changes in presynaptic and postsynaptic serotonin receptors and identify an area of prefrontal cortex that may influence suicide risk. Quantitative autoradiography was performed in coronal sections of prefrontal cortex to determine whether serotonin 5-HT1A receptor (postsynaptic in cortex) and serotonin transporter (presynaptic) binding are different in suicide victims compared to matched controls. 5-HT1A receptor binding was higher in 85 of the 103 sampled areas in the suicide group (n = 18 pairs; P < 0.0001). The increase ranged from 17 to 30%. The increase was more pronounced in the ventrolateral prefrontal cortex. Serotonin transporter binding was found to be lower in the suicide group in all but one of the 43 sampled regions (n = 22 pairs; P < 0.0001). The reduction in binding was most pronounced in the ventrolateral prefrontal cortex, where the difference between suicides and controls ranged between 15 and 27%. Serotonin transporter and 5-HT1A binding were negatively correlated (r = - 0.35 to - 0.44, P = 0.04 to 0.007) within the same brain areas, suggesting common regulatory factors with opposite effects on binding to the two receptors. We conclude that suicide victims have an abnormality in the serotonin system involving predominantly the ventrolateral prefrontal cortex, and hypothesize that the serotonergic dysfunction in this brain region contributes to the risk for suicidal behavior. C1 COLUMBIA UNIV COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,NIMH,CLIN RES CTR,NEW YORK,NY 10032. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,PITTSBURGH,PA 15213. RP ARANGO, V (reprint author), COLUMBIA UNIV COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,DEPT NEUROSCI,722 W 168TH ST,BOX 28,NEW YORK,NY 10032, USA. RI Arango, Victoria/K-9377-2015; Underwood, Mark/N-1412-2015 OI Arango, Victoria/0000-0001-8811-400X; Underwood, Mark/0000-0003-0595-8712 FU NIAAA NIH HHS [AA09004]; NIMH NIH HHS [MH40210, MH47097] NR 79 TC 317 Z9 320 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 7 PY 1995 VL 688 IS 1-2 BP 121 EP 133 DI 10.1016/0006-8993(95)00523-S PG 13 WC Neurosciences SC Neurosciences & Neurology GA RN965 UT WOS:A1995RN96500016 PM 8542298 ER PT J AU PACAK, K MCCARTY, R PALKOVITS, M KOPIN, IJ GOLDSTEIN, DS AF PACAK, K MCCARTY, R PALKOVITS, M KOPIN, IJ GOLDSTEIN, DS TI EFFECTS OF IMMOBILIZATION ON IN-VIVO RELEASE OF NOREPINEPHRINE IN THE BED NUCLEUS OF THE STRIA TERMINALIS IN CONSCIOUS RATS SO BRAIN RESEARCH LA English DT Note DE MICRODIALYSIS; DIHYDROXYPHENYLGLYCOL; DIHYDROXYPHENYLACETIC ACID ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CENTRAL AMYGDALOID NUCLEUS; CELLULAR ARCHITECTURE; STRESS; PROJECTIONS; CYTOARCHITECTURE; CORTICOSTERONE; NORADRENALINE; STIMULATION; RESPONSES AB Release of norepinepriine (NE) and its metabolites in the bed nucleus of the stria terminalis (BNST) was examined using in vivo microdialysis in conscious rats before, during and after 2 h of immobilization. Microdialysate levels of NE and of dihydroxyphenylglycol (DHPG) increased by 170-290% above basal levels during the 1st h of immobilization and decreased gradually thereafter. In contrast, levels of dihydroxyphenylacetic acid (DOPAC) increased gradually over the entire period of immobilzation, peaking at 110% above baseline levels. These findings indicate that in rats a single immobilization is attended by increased synthesis, release and reuptake of NE within the BNST. The results are consistent with previous findings relating to stress-induced release of NE in the hypothalamic paraventricular nucleus, central nucleus of the amygdala and cerebral cortex and suggest concurrent noradrenergic activation in several brains centers during acute stress. C1 UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 25 TC 77 Z9 77 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 AUG 7 PY 1995 VL 688 IS 1-2 BP 242 EP 246 DI 10.1016/0006-8993(95)00566-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA RN965 UT WOS:A1995RN96500034 PM 8542318 ER PT J AU BAKER, RA HERKENHAM, M AF BAKER, RA HERKENHAM, M TI ARCUATE NUCLEUS NEURONS THAT PROJECT TO THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS - NEUROPEPTIDERGIC IDENTITY AND CONSEQUENCES OF ADRENALECTOMY ON MESSENGER-RNA LEVELS IN THE RAT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE POMC; NPY; SOM; FLUOROGOLD; DOUBLE LABEL ID CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RIBONUCLEIC-ACID; PITUITARY ADRENOCORTICAL AXIS; BETA-ENDORPHIN; INSITU HYBRIDIZATION; GLUCOCORTICOID REGULATION; AFFERENT CONNECTIONS; TRACTUS-SOLITARIUS; SUPRAOPTIC NUCLEI; MEDIAN-EMINENCE AB The possible role that the hypothalamic arcuate nucleus might play in mediating the increase in paraventricular nucleus corticotropin-releasing hormone mRNA levels following adrenalectomy was investigated in two series of experiments. In the first series, in situ hybridization histochemistry was used to quantify levels of eight arcuate nucleus neuropeptide and neurotransmitter mRNAs in neurons that potentially relay adrenal steroid feedback to the paraventricular nucleus. In the second series of experiments, arcuate neuropeptidergic projections to the hypothalamic paraventricular nucleus were characterized using retrograde tracing in combination with in situ hybridization histochemistry. Despite an increase in paraventricular nucleus corticotropin-releasing hormone (60%) and pituitary proopiomelanocortin mRNA levels (sixfold), arcuate mRNA levels for proopiomelanocortin, neuropeptide Y, somatostatin, galanin, dynorphin, tyrosine hydroxylase, glutamate decarboxylase, and the glucocorticoid receptor were unchanged 14 days following adrenalectomy. Neuropeptidergic characterization of arcuatoparaventricular projections was achieved by injection of the retrograde tracer fluorogold into the paraventricular nucleus; retrogradely labeled neurons were characterized with polyclonal antisera against fluorogold in combination with oligonucleotide probes directed against neuropeptide Y, proopiomelanocortin, or somatostatin. Out of these three arcuate neuropeptides, neuropeptide Y mRNA was contained in 18% of the fluorogold-positive neurons in the arcuate, proopiomelanocortin mRNA was contained in 8%, and somatostatin mRNA was contained in 6%. Overall, the results from both experiments suggest that the arcuatoparaventricular neuropeptide Y, proopiomelanocortin, and somatostatin projections are not sensitive to a chronic (14 day) lack of adrenal steroids. These projections as well as the other arcuate neurotransmitter and neuropeptide systems appear not to contribute to the persistent elevations in paraventricular nucleus corticotropin-releasing hormone mRNA levels or pituitary proopiomelanocortin mRNA levels found in 14 day adrenalectomized rats. (C) 1995 Wiley-Liss, Inc.* RP BAKER, RA (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D-15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 76 TC 145 Z9 146 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 AUG 7 PY 1995 VL 358 IS 4 BP 518 EP 530 DI 10.1002/cne.903580405 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RL458 UT WOS:A1995RL45800004 PM 7593746 ER PT J AU SCHOEN, TJ MAZURUK, K CHADER, GJ RODRIGUEZ, IR AF SCHOEN, TJ MAZURUK, K CHADER, GJ RODRIGUEZ, IR TI ISOLATION OF CANDIDATE GENES FOR MACULAR DEGENERATION USING AN IMPROVED SOLID-PHASE SUBTRACTIVE CLONING TECHNIQUE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article AB An improved solid-phase subtraction procedure was developed to generate a readily amplifiable library of short cDNA fragments highly enriched in the macula (target) versus the peripheral region (driver) of the monkey neural retina. The generated clones were sequenced and 63 were analyzed by northern blotting using total RNA from the monkey macula and peripheral retina. The results indicate that 32% are highly enriched in macula, 36% are below the limits of detection and 32% are not enriched. No clones were found which were enriched in the peripheral retina. Our technique is therefore successful in identifying novel cDNAs enriched in the macula area of the neural retina that may represent potential candidate genes for hereditary ocular diseases. It should thus be useful in other situations where subtle differences in expression between cell types or tissue areas need to be analyzed. (C) 1995 Academic Press, Inc. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 15 TC 10 Z9 11 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 4 PY 1995 VL 213 IS 1 BP 181 EP 188 DI 10.1006/bbrc.1995.2114 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RN594 UT WOS:A1995RN59400025 PM 7639734 ER PT J AU CRESPO, P MISCHAK, H GUTKIND, JS AF CRESPO, P MISCHAK, H GUTKIND, JS TI OVEREXPRESSION OF MAMMALIAN PROTEIN-KINASE C-ZETA DOES NOT AFFECT THE GROWTH-CHARACTERISTICS OF NIH 3T3 CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SIGNAL-TRANSDUCTION; RAT FIBROBLASTS; ISOFORM; INHIBITION; EPSILON AB The structure of protein kinase C zeta (PKCL zeta) is unusual with respect to other PKCs, as it lacks the C2 domain and possesses only one zinc finger region. Consequently, PKC zeta can not be activated by diacylglycerol or phorbol esters and is not downregulated by prolonged treatment by phorbol esters nor blocked by commonly utilized PKC inhibitors. In this study, we have explored the idea that PKC zeta might participate in proliferative pathways. Our findings show that marked overexpression of mammalian PKC zeta does not alter the growth characteristics of NIH 3T3 cells, nor induces cellular transformation. Furthermore, mammalian PKC zeta does not potentiate the transforming ability of oncogenes such as ras, sis and the muscarinic receptor m1. In this context, PKC zeta or its dominant negative mutant do not affect MAP kinase activation by oncogenes or growth factors. Taken together, our findings demonstrate that mammalian PKC zeta does not directly participate in signaling pathways involved in oncogenic transformation. (C) 1995 Academic Press, Inc. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALING LAB,BETHESDA,MD 20892. GSF MUNICH,INST CLIN MOLEC BIOL,D-81377 MUNICH,GERMANY. RI Gutkind, J. Silvio/A-1053-2009; Mischak, Harald/E-8685-2011; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 18 TC 27 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 4 PY 1995 VL 213 IS 1 BP 266 EP 272 DI 10.1006/bbrc.1995.2125 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RN594 UT WOS:A1995RN59400036 PM 7639744 ER PT J AU ACRI, JB CARTER, SR ALLING, K GETERDOUGLASS, B DIJKSTRA, D WIKSTROM, H KATZ, JL WITKIN, JM AF ACRI, JB CARTER, SR ALLING, K GETERDOUGLASS, B DIJKSTRA, D WIKSTROM, H KATZ, JL WITKIN, JM TI ASSESSMENT OF COCAINE-LIKE DISCRIMINATIVE STIMULUS EFFECTS OF DOPAMINE D-3 RECEPTOR LIGANDS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE DOPAMINE D-3 RECEPTOR; 7-OH-DPAT (7-HYDROXY-2-(N,N-DI-N-PROPYLAMINO)TETRALIN); (+)-PD128907 (4AR,10BR-(+)TRANS-3,4,4A,10B-TETRAHYDRO-4-N-PROPYL-2H,5H[4,3-B]-1,4-OXA ZIN-9-OL) ID RAT AB The highly selective dopamine D-3 receptor ligand, (+)-PD 128907 4aR10bR-(+)-trans-3,4,4a,10b-tetrahydro-4-n-propyl- 2H5H[4,3-b]-1,4-oxazin-9-ol), and other dopamine D-3 receptor ligands, (+/-)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin and (+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin, substituted for the discriminative stimulus effects of cocaine in rats, an animal model of subjective effects in humans. Substitution only occurred at doses that markedly decreased responding. These results suggest that dopamine D-3 receptors may be involved in the subjective effects of cocaine, and therefore may be a target for the discovery of treatments for cocaine dependence. C1 UNIV GRONINGEN,DEPT MED CHEM,9713 AW GRONINGEN,NETHERLANDS. RP ACRI, JB (reprint author), NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 8 TC 68 Z9 68 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 4 PY 1995 VL 281 IS 2 BP R7 EP R9 DI 10.1016/0014-2999(95)00411-D PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RN827 UT WOS:A1995RN82700016 PM 7589197 ER PT J AU RISINGER, JI UMAR, A BARRETT, JC KUNKEL, TA AF RISINGER, JI UMAR, A BARRETT, JC KUNKEL, TA TI A HPMS2 MUTANT-CELL LINE IS DEFECTIVE IN STRAND-SPECIFIC MISMATCH REPAIR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID NONPOLYPOSIS COLON-CANCER; SACCHAROMYCES-CEREVISIAE; GENETIC INSTABILITY; COLORECTAL-CANCER; DNA; MUTATIONS; TOLERANT; HOMOLOG AB Human cells contain several homologs of the bacterial mutL gene required for mismatch repair, including a gene on chromosome 7 designated hPMS2. We have identified an endometrial carcinoma cell line, HEC-1-A, that has a C --> T mutation in hPMS2 that generates a nonsense codon and yields a protein truncated at the C terminus, No wild-type gene or gene product was detected, The missing amino acids in hPMS2 are highly conserved among PMS homologs, suggesting that they may be critical for function, In support of this, extracts of HEC-1-A cells are defective in repairing a variety of mismatched substrates. Moreover, di-, tri-, and tetranucleotide repeated sequences are highly unstable in single cell clones of HEC-1-A cells, and HEC-1-A cells are resistant to killing by N-methyl-N'-nitro-N-nitrosoguanidine. The results provide strong experimental support for the involvement of the hPMS2 gene product in mismatch repair in human cells and support the concept that a defective hPMS2 gene may lead to predisposition to certain forms of cancer. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27599. NR 36 TC 94 Z9 94 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 AUG 4 PY 1995 VL 270 IS 31 BP 18183 EP 18186 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM642 UT WOS:A1995RM64200003 PM 7629132 ER PT J AU KANG, KR WOLFF, EC PARK, MH FOLK, JE CHUNG, SN AF KANG, KR WOLFF, EC PARK, MH FOLK, JE CHUNG, SN TI IDENTIFICATION OF YHR068W IN SACCHAROMYCES-CEREVISIAE CHROMOSOME-VIII AS A GENE FOR DEOXYHYPUSINE SYNTHASE - EXPRESSION AND CHARACTERIZATION OF THE ENZYME SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYPUSINE; PROTEIN; SPERMIDINE; YEAST; PURIFICATION; CLEAVAGE AB Deoxyhypusine synthase catalyzes the formation of deoxyhypusine, the first step in hypusine biosynthesis. Amino acid sequences of five tryptic peptides from rat deoxyhypusine synthase were found to match partially the deduced amino acid sequence of the open reading frame of gene YHR068w of Saccharomyces cerevisiae chromosome VIII (AC:U00061). In order to determine whether the product of this gene corresponds to yeast deoxyhypusine synthase, a 1.17-kilobase pair cDNA with an identical nucleotide sequence to that of the YR068w coding region was obtained from S. cerevisiae cDNA by polymerase chain reaction and was expressed in Escherichia coli B strain BL21(DE3). The recombinant protein was found mostly in the E. coli cytosol fraction and comprised similar to 20% of the total soluble protein. The purified form of the expressed protein effectively catalyzed the formation of deoxyhypusine in yeast eIF-5A precursors as well as in human precursor and in those from Chinese hamster ovary cells. The molecular mass of the enzyme was estimated to be 172,000 a 4,300 Da by equilibrium centrifugation. The mass of its polypeptide subunit was determined to be similar to 43,000 Da, in close agreement with that calculated for the coding region of the YHR068w gene. These findings show that this gene is a coding sequence for yeast deoxyhypusine synthase and that the product of this gene exists in a tetrameric form. C1 NIDR,CELLULAR DEV & ONCOL LAB,ENZYME CHEM SECT,BETHESDA,MD 20892. NR 22 TC 40 Z9 42 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 AUG 4 PY 1995 VL 270 IS 31 BP 18408 EP 18412 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM642 UT WOS:A1995RM64200042 PM 7629166 ER PT J AU WONG, JM SHI, YB AF WONG, JM SHI, YB TI COORDINATED REGULATION OF AND TRANSCRIPTIONAL ACTIVATION BY XENOPUS THYROID-HORMONE AND RETINOID-X RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; AMPHIBIAN METAMORPHOSIS; RESPONSE ELEMENTS; ACID RECEPTORS; BETA GENES; LAEVIS AB Thyroid hormone (T-3) plays a causative role in amphibian metamorphosis, This regulation is thought to be mediated by heterodimers of T-3 receptors (TRs) and retinoid X receptors (RXRs). We report here that Xenopus TRs can indeed form strong heterodimers with Xenopus RXRs on the T-3 response element (TRE) present in Xenopus TRP beta genes. Using a T-3-responsive in vivo tran scription system established by introducing TRs and RXRs into Xenopus oocytes, we demonstrated that TR-RXR heterodimers repressed TR beta gene promoter in the absence of T-3 and activated the promoter in the presence of the hormone. Furthermore, by analyzing the expression of TR and RXR genes, we showed that TR and RXR genes were coordinately regulated in different tissues during metamorphosis. Thus high levels of their mRNAs are present in the limb during early stages of limb development when morphogenesis occurs and in the tail toward the end of metamorphosis when it is being resorbed. Such correlations coupled with our TRE-binding and in vivo transcriptional activation experiments provide strong evidence that TRs and RXRs function together to mediate the effects of T-3 during metamorphosis, These results further suggest a possible molecular basis for the temporal regulation of tissue-specific metamorphosis. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 32 TC 111 Z9 112 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 AUG 4 PY 1995 VL 270 IS 31 BP 18479 EP 18483 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM642 UT WOS:A1995RM64200052 PM 7629175 ER PT J AU YANG, Y MINUCCI, S OZATO, K HEYMAN, RA ASHWELL, JD AF YANG, Y MINUCCI, S OZATO, K HEYMAN, RA ASHWELL, JD TI EFFICIENT INHIBITION OF ACTIVATION-INDUCED FAS LIGAND UP-REGULATION AND T-CELL APOPTOSIS BY RETINOIDS REQUIRES OCCUPANCY OF BOTH RETINOID-X RECEPTORS AND RETINOIC ACID RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; THYROID-HORMONE; SURFACE ANTIGEN; CYCLOSPORINE-A; GLUCOCORTICOID RECEPTOR; DIRECT REPEAT; BINDING-SITE; CYCLE BLOCK; DNA-BINDING; ALL-TRANS AB Two retinoic acid (RA) receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), have been identified. All-trans-RA and its 9-cis-isomer are ligands for RARs, but only 9-cis-RA binds RXRs with high affinity, Activation-induced T cell hybridoma death is mediated via the engagement of Fas by activation-up-regulated Fas ligand, and RA prevents this type of apoptosis by inhibiting the induction of Fas ligand expression. To investigate the mechanism of RA action, T hybridoma cells were transfected with cDNA encoding RXR beta or dominant-negative RXR beta. Cells that overexpressed RXR beta were more sensitive to 9-cis-RA rescue from activation-induced death than cells transfected with vector alone, In contrast, cells expressing the dominant-negative RXR beta could not be rescued from death with 9-cis-RA. In wild type cells, an RAR-selective synthetic retinoid had little effect on activation-induced apoptosis, while an RXR-selective agonist prevented apoptosis but only at concentrations about similar to 10-fold greater than that required for 9-cis-RA. Simultaneous addition of the RAR- and RXR-selective retinoids completely prevented activation-induced apoptosis at concentrations where either alone had relatively little protective effect, The same hierarchy of efficacy was found for activation-induced Fas ligand expression, These data demonstrate that binding of both RARs and RXRs is required for efficient inhibition of activation-induced Fas ligand up-regulation and T cell apoptosis by retinoic acid. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. LIGAND PHARMACEUT INC,SAN DIEGO,CA 92121. RI Minucci, Saverio/J-9669-2012 NR 72 TC 57 Z9 59 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 AUG 4 PY 1995 VL 270 IS 31 BP 18672 EP 18677 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM642 UT WOS:A1995RM64200081 PM 7629199 ER PT J AU CHOLODY, WM HERNANDEZ, L HASSNER, L SCUDIERO, DA DJURICKOVIC, DB MICHEJDA, CJ AF CHOLODY, WM HERNANDEZ, L HASSNER, L SCUDIERO, DA DJURICKOVIC, DB MICHEJDA, CJ TI BISIMIDAZOACRIDONES AND RELATED-COMPOUNDS - NEW ANTINEOPLASTIC AGENTS WITH HIGH SELECTIVITY AGAINST COLON TUMORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA BIFUNCTIONAL INTERCALATORS; ACRIDINE ETHIDIUM HETERODIMER; ANTICANCER AGENTS; MURINE LEUKEMIAS; DEOXYRIBONUCLEIC-ACID; BIOLOGICAL-ACTIVITY; CELL-LINES; BINDING; SERIES; DIMERS AB A new class of potent and highly selective antitumor agents has been synthesized. Bisimidazoacridones, where the tetracyclic ring systems are held together by either a N-2-methyldiethylenetriamine or 3,3'-diamino-N-methyldipropylamine linker, and related asymmetrical compounds, where one of the imidazoacridone ring system was replaced by a triazoloacridone ring system, were found to be cytostatic and cytotoxic in vitro. Some of these compounds, such as 5,5'-[(methylimino)bis(3,1-propanediylimino)]bis[6H-imidazo[4,5,1-de]acridim-6-one] (4b) showed remarkably high activity and selectivity for colon cancer in the National Cancer Institute screen. This antitumor effect was also apparent in colony survival assays utilizing the colon cancer line, HCT-116, and in in vivo assays involving xenografts of tumor derived from HCT-116 in nude mice. The tested compounds exhibited relatively low acute toxicity and were well tolerated by the treated animals. The bisimidazoacridones interact with nucleic acids in vitro but preliminary experimental and modeling data indicate that in spite of their structure, they may not be bis-intercalators. While the precise mode of action of these compounds is not yet understood, they appear to be excellent candidates for clinical development. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,LAB ANIM SCI PROGRAM,FREDERICK,MD 21702. RP CHOLODY, WM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,MSL,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-46000] NR 43 TC 70 Z9 70 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 4 PY 1995 VL 38 IS 16 BP 3043 EP 3052 DI 10.1021/jm00016a007 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RN657 UT WOS:A1995RN65700007 PM 7636867 ER PT J AU LEE, YB PARK, MH FOLK, JE AF LEE, YB PARK, MH FOLK, JE TI DIAMINE AND TRIAMINE ANALOGS AND DERIVATIVES AS INHIBITORS OF DEOXYHYPUSINE SYNTHASE - SYNTHESIS AND BIOLOGICAL-ACTIVITY SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EUKARYOTIC INITIATION FACTOR-5A; HYPUSINE; SPERMIDINE; PROTEIN; PROLIFERATION; CLEAVAGE; CELLS; ACID AB Deoxyhypusine synthase catalyzes the initial step in the posttranslational formation of the amino acid hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic initiation factor 5A (eIF-5A). eIF-5A and its hypusine modification are believed to be essential for cell growth. A number of compounds related to diamines and triamines were synthesized and tested as inhibitors of this enzyme. The findings indicate that the long chain triamines 2a and 2b and their guanyl derivatives 3a, 3b, 4a, and 4b exert inhibition by binding to enzyme through only a portion of their structures at any one time. The inhibition exhibited by N-ethyl-1,7-diaminoheptane 20 and its guanyl derivative 21 supports this notion and is evidence for participation of the secondary amino group in binding to enzyme. There is preliminary evidence that amidino and isothiuronium groups may also serve as basic centers for binding to enzyme. Few of the compounds tested here were comparable in inhibitory potency to 1-guanidino-7-aminoheptane (GC(7)) the most effective known inhibitor of deoxhypusine synthase, and none proved nearly as efficient as GC(7) in inhibiting the enzyme in Chinese hamster ovary cells. Hence, unlike the antiproliferative effect of GC(7), for which there is evidence of cause by interference with deoxhypusine synthase catalysis (Park, M. H.; Wolff, E. C.; Lee, Y. B.; Folk, J. E. J. Biol. Chem. 269, 1994, 27827-27832), of the newly synthesized compounds cannot be the effective growth arrest exerted by several attributed to inhibition of hypusine synthesis. RP LEE, YB (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,ENZYME CHEM SECT,BLDG 30,ROOM 211,30 CONVENT DR,MSC 4330,BETHESDA,MD 20892, USA. NR 37 TC 45 Z9 47 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 4 PY 1995 VL 38 IS 16 BP 3053 EP 3061 DI 10.1021/jm00016a008 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RN657 UT WOS:A1995RN65700008 PM 7636868 ER PT J AU WOLFOVITZ, E PACAK, K ABASSI, Z KOPIN, IJ GOLDSTEIN, DS AF WOLFOVITZ, E PACAK, K ABASSI, Z KOPIN, IJ GOLDSTEIN, DS TI EFFECTS OF HYPERCORTISOLEMIA OR HYPERINSULINEMIA ON NEUROCHEMICAL INDEXES OF CATECHOLAMINE RELEASE AND SYNTHESIS IN CONSCIOUS RATS SO JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM LA English DT Article DE INSULIN; CORTISOL; DOPA; DOPAMINE ID SYMPATHETIC NERVOUS-SYSTEM; PLASMA DOPA RESPONSES; URINARY DOPAMINE; INSULIN; HUMANS; DIHYDROXYPHENYLALANINE; NOREPINEPHRINE; BLOOD; 3,4-DIHYDROXYPHENYLALANINE; SENSITIVITY AB Glucocorticoids and insulin (INS) complexly affect sympathoneural and adrenomedullary outflows. This study assessed effects of chronic hypercortisolemia and effects of INS independent of INS-induced hypoglycemia on neurochemical indices of different aspects of catecholaminergic function in conscious rats. Since r-DOPA is the precursor of the endogenous catecholamines and the immediate product of the rate-limiting enzymatic step in catecholamine biosynthesis, alterations in rates of appearance (spillover) of L-DOPA in arterial plasma may reflect alterations in catecholamine synthesis. The study therefore included examination of whether cortisol (CORT) or INS affects L-DOPA spillover or renal excretion of dopamine (DA) derived from plasma L-DOPA. Arterial plasma levels and urinary excretion rates of endogenous catechols and radiolabelled L-DOPA and DA were measured during systemic intravenous infusions of [H-3]L-DOPA. CORT was administered via a subcutaneous minipump reservoir for one week prior to [H-3]L-DOPA infusion, and INS was infused with glucose to examine effects of hyperinsulinemia independently of hypoglycemia. CORT decreased plasma levels and urinary excretion of norepinephrine (NE). INS did not. Neither CORT nor INS affected levels of other catechols, L-DOPA spillover, or the rate of urinary excretion of [H-3]DA for a given plasma level of [H-3]L-DOPA. The results suggest that CORT inhibits sympathetically-mediated NE release without altering overall rates of catecholamine turnover or synthesis in sympathetic nerves in vivo and that INS effects on catecholaminergic function depend entirely on INS-induced hypoglycemia. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 36 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1838 J9 J AUTONOM NERV SYST JI J. Auton. Nerv. Syst. PD AUG 4 PY 1995 VL 54 IS 2 BP 104 EP 112 DI 10.1016/0165-1838(94)00192-M PG 9 WC Neurosciences SC Neurosciences & Neurology GA RQ393 UT WOS:A1995RQ39300002 PM 7499722 ER PT J AU RANDAD, RS LUBKOWSKA, L BHAT, TN MUNSHI, S GULNIK, SV YU, B ERICKSON, JW AF RANDAD, RS LUBKOWSKA, L BHAT, TN MUNSHI, S GULNIK, SV YU, B ERICKSON, JW TI SYMMETRY-BASED HIV PROTEASE INHIBITORS - RATIONAL DESIGN OF 2-METHYLBENZAMIDES AS NOVEL P2/P2' LIGANDS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID RETROVIRAL PROTEASES; CRYSTAL-STRUCTURE AB Readily accessible, non-peptidic, achiral 2-methylbenzamides were designed to serve as P2/P2' ligands for symmetry-based inhibitors of HIV-1 Protease. Introduction of 3-hydroxy substituent provided a potent inhibitor 7 (K-i = 0.8 nM). RP RANDAD, RS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 22 TC 13 Z9 14 U1 0 U2 2 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 AUG 3 PY 1995 VL 5 IS 15 BP 1707 EP 1712 DI 10.1016/0960-894X(95)00289-6 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA RM790 UT WOS:A1995RM79000028 ER PT J AU MUDD, SH LEW, HL AF MUDD, SH LEW, HL TI PLASMA HOMOCYST(E)INE OR HOMOCYSTEINE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 CHILDRENS HOSP,BOSTON,MA 02115. RP MUDD, SH (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 5 TC 33 Z9 34 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 3 PY 1995 VL 333 IS 5 BP 325 EP 325 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RL694 UT WOS:A1995RL69400035 PM 7596391 ER PT J AU BOICE, JD MANDEL, JS DOODY, MM AF BOICE, JD MANDEL, JS DOODY, MM TI BREAST-CANCER AMONG RADIOLOGIC TECHNOLOGISTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FOLLOW-UP; RISK; RADIATION; THERAPY; MORTALITY; WORKERS; TUBERCULOSIS; EPIDEMIOLOGY; RADIOTHERAPY; CHILDHOOD AB Objective.-To evaluate the risk of breast cancer among women occupationally ex Design.-Case-control study. Participants.-A health survey of 105 385 women radiologic technologists certified by the American Registry of Radiologic Technologists since 1926. Among 79016 respondents, 600 breast cancer cases were identified. Each of 528 eligible subjects with breast cancer was matched to five control subjects based on age, year of certification, and follow-up time. Main Outcome Measures.-Relative risk (RR) estimated as the relative odds ratio for breast cancer over categories of years worked as a radiologic technologist and according to personal and occupational exposure characteristics. Results.-Study subjects had been certified for a mean of 29 years; 63.8% of cases and 62.6% of controls worked as radiologic technologists for 10 years or more. Significant increased risks for breast cancer were associated with early age at menarche (for <11 years of age: RR=1.79; 95% confidence interval [CI], 1.09 to 2.94), nulliparity (RR=1.36; 95% CI, 1.04 to 1.78), first-degree relative with history of breast cancer(RR=2.07; 95% CI, 1.56 to 2.74), prior breast biopsy (RR=1.53; 95% CI, 1.17 to 2.00), alcohol consumption (for >14 alcoholic drinks per week: RR=2.12; 95% CI, 1.06 to 4.27), thyroid cancer (RR=5.36; 95% CI, 1.64 to 17.5), hyperthyroidism (RR=1.66; 95% CI, 1.02 to 2.71), and residence in the northeastern United States (RR=1.66; 95% CI, 1.19 to 2.30). Jobs involving radiotherapy, radioisotopes, or fluoroscopic equipment, however, were not linked to breast cancer risk, nor were personal exposures to fluoroscopy or multifilm procedures. Use of birth control pills, postmenopausal estrogens, or permanent hair dyes also were not risk factors. Based on dosimetry records for 35% of study subjects, cumulative exposures appeared low. Among women who worked more than 20 years, the RR for breast cancer was 1.13 (95% CI, 0.79 to 1.64). Conclusions.-More than 50% of the reported breast cancers could be explained by established risk factors. Employment as a radiologic technologist, however, was not found to increase the risk of breast cancer. The contribution of prolonged exposure to relatively low doses of ionizing radiation to breast cancer risk was too small to be detectable at this time. C1 UNIV MINNESOTA, SCH PUBL HLTH, DIV ENVIRONM & OCCUPAT HLTH, MINNEAPOLIS, MN USA. RP BOICE, JD (reprint author), NCI, RADIAT EPIDEMIOL BRANCH, 6130 EXECUT BLVD, EPN ROOM 408, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N01-CP0-5609, N01-CP8-5604, N01-CP9-5614] NR 42 TC 45 Z9 45 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 2 PY 1995 VL 274 IS 5 BP 394 EP 401 DI 10.1001/jama.274.5.394 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA RL416 UT WOS:A1995RL41600025 PM 7616635 ER PT J AU LAND, CE AF LAND, CE TI STUDIES OF CANCER AND RADIATION-DOSE AMONG ATOMIC-BOMB SURVIVORS - THE EXAMPLE OF BREAST-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IONIZING-RADIATION; MORTALITY; THERAPY; WOMEN; RISK AB A comprehensive program of medical follow-up of survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, by the Radiation Effects Research Foundation (RERF) has produced quantitative estimates of cancer risk from exposure to ionizing radiation. For breast cancer in women, in particular, the strength of the radiation dose response and the generally low level of population risk in the absence of radiation exposure have led to a clear description of excess risk and its variation by age at exposure and over time following exposure. Comparisons of RERF data with data from medically irradiated populations have yielded additional information on the influence of population and underlying breast cancer rates on radiation-related risk. Epidemiological investigations of breast cancer cases and matched controls among atomic bomb survivors have clarified the role of reproductive history as a modifier of the carcinogenic effects of radiation exposure. Finally, a pattern of radiation-related risk by attained age among the survivors exposed during childhood or adolescence suggests the possible existence of a radiation-susceptible subgroup. The hypothetical existence of such a group is lent plausibility by the results of recent family studies suggesting that heritable mutations in certain genes are associated with familial aggregations of breast cancer. The recent isolation and cloning of one such gene, BRCA1, makes it likely that the hypothesis can be tested using molecular assays of archival and other tissue obtained from atomic bomb survivor cases and controls. RP LAND, CE (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,EPN 408,6130 EXECUT BLVD,MS 7362,BETHESDA,MD 20892, USA. NR 33 TC 63 Z9 64 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 AUG 2 PY 1995 VL 274 IS 5 BP 402 EP 407 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RL416 UT WOS:A1995RL41600026 PM 7616636 ER PT J AU SCHATZKIN, A GOLDSTEIN, A FREEDMAN, LS AF SCHATZKIN, A GOLDSTEIN, A FREEDMAN, LS TI WHAT DOES IT MEAN TO BE A CANCER GENE CARRIER - PROBLEMS IN ESTABLISHING CAUSALITY FROM THE MOLECULAR-GENETICS OF CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; CYSTIC-FIBROSIS; BREAST-CANCER; NONSENSE MUTATION; COLON-CANCER; MILD; SPECTRUM; HOMOLOG; DISEASE; RISK AB This article addresses the following question: What does it mean to be a cancer gene carrier? The existence of families prone to cancer has prompted an intense search for predisposing heritable gene mutations. Genes that impart susceptibility to colorectal, breast, and ovarian cancers have been recently identified. It is doubtful, however, that the action of a single mutant gene totally accounts for the development of malignant disease. The mutant gene likely causes cancer in these family members only in conjunction with other genes, environmental factors, or both. Furthermore, although an individual carrier of a mutant gene within a cancer-prone family has an increased risk of malignancy, nutritional, pharmacologic, or other interventions may still confer protection. Extrapolations from cancer-prone families to the general population are even more problematic. The excess risk of malignancy among carriers of mutant genes who are not members of cancer-prone families is unknown. Large-scale epidemiologic studies are needed to determine the magnitude (or even the existence) of such excess risk. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 35 TC 21 Z9 21 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 AUG 2 PY 1995 VL 87 IS 15 BP 1126 EP 1130 DI 10.1093/jnci/87.15.1126 PG 5 WC Oncology SC Oncology GA RL102 UT WOS:A1995RL10200009 PM 7674316 ER PT J AU BROWN, ML KESSLER, LG AF BROWN, ML KESSLER, LG TI THE USE OF GENE TESTS TO DETECT HEREDITARY PREDISPOSITION TO CANCER - ECONOMIC-CONSIDERATIONS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; COST-EFFECTIVENESS; COLON-CANCER; FREQUENCY; HOMOLOG AB Several mutations recently have been shown to be associated with hereditary nonpolyposis colon cancer (HNPCC) in families displaying unusually strong predisposition to colorectal cancer. Laboratory tests to detect such gene mutations soon will be commercially available, raising the possibility for population-wide screening. The purpose of this study was to explore the economic implications of conducting a population-wide screening for HNPCC compared with restricted screening among members of the families at high risk. An exploratory analysis was performed to determine which factors are most important in determining the cost-effectiveness of such a testing program. The base-case analysis focuses on current uncertainty about the population prevalence of the HNPCC genotype and phenotype. The uncertainty with regard to parameters related to the cost-effectiveness of screening and preventive interventions for HNPCC were explored, using additional sensitivity analyses, Cost-effectiveness is achieved for population-wide screening only when assumptions most favorable to that outcome are made regarding the HNPCC prevalence, the cost and effectiveness of screening, and preventive intervention. Information on the population prevalence of HNPCC genotypes and the penetrance of these genotypes is essential for making policy decisions. Additional information is needed regarding the determinants of the cost of genetic testing and counseling, the efficacy of preventive regimens for individuals at high risk, and the accuracy and cost of alternative methods of identifying families at risk. C1 NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. NR 41 TC 36 Z9 36 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 AUG 2 PY 1995 VL 87 IS 15 BP 1131 EP 1136 DI 10.1093/jnci/87.15.1131 PG 6 WC Oncology SC Oncology GA RL102 UT WOS:A1995RL10200010 PM 7674317 ER PT J AU BAKER, SG FREEDMAN, LS AF BAKER, SG FREEDMAN, LS TI POTENTIAL IMPACT OF GENETIC TESTING ON CANCER PREVENTION TRIALS, USING BREAST-CANCER AS AN EXAMPLE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RISK AB Using breast cancer as an example, we explored the potential impact that a highly predictive genetic test could have on the design and analysis of cancer prevention trials. We discuss three situations in this article: 1) trials that are in progress when the genetic test first becomes available as a research tool but is not available for general use, 2) trials in progress when the genetic test becomes generally available to the public, and 3) trials that begin after the test becomes generally available. We have concluded that the availability of a highly predictive genetic test will provide impediments to prevention trials in the form of increased noncompliance and also will provide opportunities in the form of new trials that include only persons at very high risk of developing cancer. Such trial designs could, under favorable circumstances, substantially reduce the size, duration, and cost of cancer prevention trials. The availability of a highly predictive genetic test will make the discovery of effective interventions even more urgent, and the randomized trial will still provide the most reliable method of evaluating prevention strategies. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. NR 19 TC 15 Z9 15 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 AUG 2 PY 1995 VL 87 IS 15 BP 1137 EP 1144 DI 10.1093/jnci/87.15.1137 PG 8 WC Oncology SC Oncology GA RL102 UT WOS:A1995RL10200011 PM 7674318 ER PT J AU DSOUZA, MP MILMAN, G BRADAC, JA MCPHEE, D HANSON, CV HENDRY, RM CORCORAN, T STOTT, J FUNG, M HANSON, C LAMAN, J MASCOLA, J MCPHEE, D RASHEED, S RICHMAN, D SCHUITEMAKER, H THIRIART, C WAINBERG, M WEBER, J BEDDOWS, S TILLEY, S ROBINSON, J ZOLLAPAZNER, S KATINGER, H CUMMINS, L AF DSOUZA, MP MILMAN, G BRADAC, JA MCPHEE, D HANSON, CV HENDRY, RM CORCORAN, T STOTT, J FUNG, M HANSON, C LAMAN, J MASCOLA, J MCPHEE, D RASHEED, S RICHMAN, D SCHUITEMAKER, H THIRIART, C WAINBERG, M WEBER, J BEDDOWS, S TILLEY, S ROBINSON, J ZOLLAPAZNER, S KATINGER, H CUMMINS, L TI NEUTRALIZATION OF PRIMARY HIV-1 ISOLATES BY ANTI-ENVELOPE MONOCLONAL-ANTIBODIES SO AIDS LA English DT Article DE MONOCLONAL ANTIBODIES; PRIMARY ISOLATES; NEUTRALIZATION ASSAYS ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLYCOPROTEIN GP120; SURFACE GLYCOPROTEIN; CD4 BINDING; SOLUBLE CD4; TYPE-1; INFECTION; CHIMPANZEES; PROTECTION; CHALLENGE AB Objective: To evaluate human monoclonal antibodies (MAb) for neutralizing activity against primary HIV-1 isolates in peripheral blood mononuclear cells. Design: Neutralization activity data were obtained from 11 laboratories on a coded panel consisting of six human MAb to HIV envelope V3, CD4-binding region or gp41. Hyperimmune globulin against HIV-1 and normal human immunoglobulin G were supplied as controls. Each laboratory received pre-titered virus for use in the studies. Methods: Each laboratory measured neutralization of the MAb against laboratory strain HIVMN, genomic clone HIVJR-CSF, two subtype B and one subtype D primary isolates. Results: The titers of the centrally supplied virus stocks as determined by re-titration or back-titration varied among laboratories and were generally 10-100-fold less than provided. The neutralizing activity of each MAb varied by as much as a 1000-fold among laboratories. These differences may result from varying sensitivity in neutralization assay protocols and the differing susceptibility of primary cells to infection with HIV-1. Conclusions: To consolidate the data from multiple laboratories, the neutralization titers were compared by classifying antibodies as neutralizing if the antibody concentration for 50% virus inhibition was less than or equal to 10 mu g/ml. By this criterion, the CD4-binding region and gp41 MAb neutralized all four subtype B viruses and the subtype D isolate in a few of the laboratories. The V3 MAb neutralized only HIVMN and the closely related HIVJR-CSF viruses. C1 MACFARLANE BURNET CTR MED RES,NATL CTR HIV VIROL RES,FAIRFIELD,VIC,AUSTRALIA. CALIF DEPT HLTH SERV,VIRAL & RICKETTSIAL LAB,BERKELEY,CA. NATL INST BIOL STAND & CONTROLS,LAB A,LONDON,ENGLAND. TANOX BIOSYST INC,LAB B,HOUSTON,TX 77025. CALIF DEPT HLTH SERV,LAB C,SACRAMENTO,CA 95814. TNO,MED BIOL LAB,THE HAGUE,NETHERLANDS. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,LAB E,WASHINGTON,DC 20307. UNIV SO CALIF,LAB G,LOS ANGELES,CA 90089. UNIV CALIF SAN DIEGO,LAB H,LA JOLLA,CA 92093. NETHERLANDS RED CROSS,LAB I,AMSTERDAM,NETHERLANDS. SMITHKLINE BEECHAM BIOL,LAB J,RIXENSART,BELGIUM. MCGILL AIDS CTR,LAB K,MONTREAL,PQ,CANADA. ST MARYS HOSP,LAB L,LONDON,ENGLAND. PUBL HLTH RES INST,NEW YORK,NY 10016. UNIV CONNECTICUT,STORRS,CT 06268. NYU,MED CTR,NEW YORK,NY 10016. AGR UNIV VIENNA,VIENNA,AUSTRIA. N AMER BIOL INC,MIAMI,FL 33269. RP DSOUZA, MP (reprint author), NIAID,DIV AIDS,PATHOGENESIS & BASIC RES BRANCH,6003 EXECUT BLVD,SOLAR BLDG,ROOM 2C35,BETHESDA,MD 20892, USA. NR 45 TC 48 Z9 48 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 AUG PY 1995 VL 9 IS 8 BP 867 EP 874 DI 10.1097/00002030-199508000-00006 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RN991 UT WOS:A1995RN99100006 PM 7576320 ER PT J AU FRANCHINI, G ROBERTGUROFF, M TARTAGLIA, J AGGARWAL, A ABIMIKU, A BENSON, J MARKHAM, P LIMBACH, K HURTEAU, G FULLEN, J ALDRICH, K MILLER, N SADOFF, J PAOLETTI, E GALLO, RC AF FRANCHINI, G ROBERTGUROFF, M TARTAGLIA, J AGGARWAL, A ABIMIKU, A BENSON, J MARKHAM, P LIMBACH, K HURTEAU, G FULLEN, J ALDRICH, K MILLER, N SADOFF, J PAOLETTI, E GALLO, RC TI HIGHLY ATTENUATED HIV TYPE-2 RECOMBINANT POXVIRUSES, BUT NOT HIV-2 RECOMBINANT SALMONELLA VACCINES, INDUCE LONG-LASTING PROTECTION IN RHESUS MACAQUES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; TOXIC LYMPHOCYTES-T; CONFERS PROTECTION; CYNOMOLGUS MONKEYS; CYTOTOXIC LYMPHOCYTES; SYNTHETIC PEPTIDES; EXPRESSION VECTOR; ORAL SALMONELLA; SIV INFECTION; ENVELOPE AB Immunization schemes employing priming with vector-based vaccine candidates followed by subunit booster administrations have been explored and shown to have merit in the human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus systems, In this study, we have assessed the priming capacity of highly attenuated poxvirus vector (NYVAC and ALVAC)-based HIV-2 recombinants, as well as Salmonella typhimurium HIV-2 recombinants in rhesus macaques, ALVAC- and NYVAC-based vaccine candidates expressing the HIV-2 gag, pol, and env genes or NYVAC-based recombinants expressing either gp160 or gp120 were used to immunize rhesus macaques in combination protocols with alum-adjuvanted HIV-2 rgp160, Following intravenous challenge exposure with 100 infectious doses of the HIV-2(SBL6669) parental virus genotype mixture, seven of eight animals were protected from infection. The seven protected animals were rechallenged 6 months postprimary challenge, without additional booster inoculations, with the same dose of the HIV-2(SBL6669) parental virus. Five of the seven animals remained protected against HIV-2 infection at 6 months following the second challenge. In contrast, oral immunization with recombinant Salmonella expressing the HIV-2 gag and the gp120 portion of the envelope either alone or in combination with alum-adjuvanted rgp160 failed to confer protection. These results suggest that the NYVAC- and ALVAC-based recombinants may confer long-lasting protection and that these two highly attenuated poxvirus vaccine vectors may represent promising candidates for developing an acquired immunodeficiency syndrome vaccine. C1 VIROGENET CORP,TROY,NY 12180. ADV BIOSCI LABS,KENSINGTON,MD 20895. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A11,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 60 TC 55 Z9 55 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1995 VL 11 IS 8 BP 909 EP 920 DI 10.1089/aid.1995.11.909 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RN993 UT WOS:A1995RN99300005 PM 7492438 ER PT J AU GOLDMAN, D AF GOLDMAN, D TI IDENTIFYING ALCOHOLISM VULNERABILITY ALLELES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 1994 Annual Meeting of the Research-Society-on-Alcoholism CY JUN, 1994 CL MAUI, HI SP Res Soc Alcoholism DE SEROTONIN RECEPTORS; LINKAGE ANALYSIS; DIRECT GENE ANALYSIS; SSCP; DRD2 ID DOPAMINE-RECEPTOR GENE; IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; MONOAMINE METABOLITES; AMINE METABOLITES; VIOLENT OFFENDERS; ASSOCIATION; SUICIDE; POLYMORPHISM AB Identification of vulnerability alleles is one starting point for elucidating the web of interactions leading to alcoholism so that treatment and prevention can be improved. Heritability studies indicate that vulnerability alleles exist. Two molecular approaches for identifying them, direct analysis of candidate genes and genetic linkage, are highlighted in this review. Methodological problems that have been partially addressed and limitations for the applicability of the genetic findings are discussed. RP GOLDMAN, D (reprint author), NIAAA,NEUROGENET LAB,FLOW BLDG ROOM 2,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 71 TC 14 Z9 14 U1 2 U2 2 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 AUG PY 1995 VL 19 IS 4 BP 824 EP 831 DI 10.1111/j.1530-0277.1995.tb00953.x PG 8 WC Substance Abuse SC Substance Abuse GA RP721 UT WOS:A1995RP72100006 PM 7485826 ER PT J AU LANDS, WEM AF LANDS, WEM TI CELLULAR SIGNALS IN ALCOHOL-INDUCED LIVER-INJURY - A REVIEW SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review ID PLATELET-ACTIVATING-FACTOR; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; PERFUSED-RAT-LIVER; MICROTUBULE DEPOLYMERIZING AGENTS; ETHANOL-INDUCED VASOCONSTRICTION; VASCULAR ENDOTHELIAL-CELLS; HIGH-MOLECULAR-WEIGHT; ACID-BINDING PROTEIN; FAT-STORING CELLS RP LANDS, WEM (reprint author), NIAAA,DIV BASIC RES,BETHESDA,MD 20892, USA. NR 112 TC 63 Z9 64 U1 0 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 AUG PY 1995 VL 19 IS 4 BP 928 EP 938 DI 10.1111/j.1530-0277.1995.tb00969.x PG 11 WC Substance Abuse SC Substance Abuse GA RP721 UT WOS:A1995RP72100021 PM 7485841 ER PT J AU BORKOWSKI, A BENNETT, WP JONES, RT BORKOWSKI, P HARRIS, CC FERREIRA, LR KAO, GF TRUMP, BF AF BORKOWSKI, A BENNETT, WP JONES, RT BORKOWSKI, P HARRIS, CC FERREIRA, LR KAO, GF TRUMP, BF TI QUANTITATIVE IMAGE-ANALYSIS OF P53 PROTEIN ACCUMULATION IN KERATOACANTHOMAS SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE CARCINOGENESIS; KERATOACANTHOMA; P53; SKIN CANCER; SQUAMOUS CARCINOMA; TUMOR SUPPRESSOR GENE ID SQUAMOUS-CELL CARCINOMA; SKIN-CANCER; MUTANT P53; MUTATIONS; EXPRESSION; GENE AB Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers, Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear stain ing was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis. C1 UNIV MARYLAND,SCH MED,DEPT DERMATOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH DENT,DEPT ORAL PATHOL,BALTIMORE,MD 21201. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. MT SINAI MED CTR,DEPT PATHOL,MIAMI BEACH,FL 33140. NR 23 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD AUG PY 1995 VL 17 IS 4 BP 335 EP 338 PG 4 WC Dermatology SC Dermatology GA RM670 UT WOS:A1995RM67000005 PM 8600795 ER PT J AU PHILIP, RN REINHARD, KR LACKMAN, DB AF PHILIP, RN REINHARD, KR LACKMAN, DB TI OBSERVATIONS ON A MUMPS EPIDEMIC IN A VIRGIN POPULATION (REPRINTED FROM AM J HYG, VOL 69, PG 91-111, 1959) SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Reprint C1 US PHS,NIAID,ROCKY MT LAB,HAMILTON,MT. RP PHILIP, RN (reprint author), US PHS,ARCTIC HLTH RES CTR,DEPT HLTH EDUC & WELFARE,ANCHORAGE,AK, USA. NR 45 TC 5 Z9 5 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 AUG 1 PY 1995 VL 142 IS 3 BP 233 EP 253 PG 21 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RM557 UT WOS:A1995RM55700002 PM 7631629 ER PT J AU HOWARD, BV LEE, ET COWAN, LD FABSITZ, RR HOWARD, WJ OOPIK, AJ ROBBINS, DC SAVAGE, PJ YEH, JL WELTY, TK AF HOWARD, BV LEE, ET COWAN, LD FABSITZ, RR HOWARD, WJ OOPIK, AJ ROBBINS, DC SAVAGE, PJ YEH, JL WELTY, TK TI CORONARY HEART-DISEASE PREVALENCE AND ITS RELATION TO RISK-FACTORS IN AMERICAN-INDIANS - THE STRONG HEART-STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CORONARY DISEASE; DIABETES MELLITUS; HYPERTENSION; INDIANS, NORTH AMERICAN; INSULIN; LIPOPROTEINS; OBESITY ID DEPENDENT DIABETES-MELLITUS; PIMA-INDIANS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; GLUCOSE-TOLERANCE; ALASKA NATIVES; BLOOD-PRESSURE; INSULIN; MORTALITY; POPULATION AB Although coronary heart disease (CHD) is currently the leading cause of death among American Indians, information on the prevalence of CHD and its association with known cardiovascular risk factors is limited. The Strong Heart Study was initiated in 1988 to quantify cardiovascular disease and its risk factors among three geographically diverse groups of American Indians. Members of 13 Indian communities in Arizona, Oklahoma, and South and North Dakota between 45 and 74 years of age underwent a physical examination that included medical history; an electrocardiogram; anthropometric and blood pressure measurements; an oral glucose tolerance test; and measurements of fasting plasma lipoproteins, fibrinogen, insulin, hemoglobin A1(c), and urinary albumin. Prevalence rates of definite myocardial infarction and definite CHD were higher in men than in women at all three centers (p < 0.0001) and higher in those with diabetes mellitus (p = 0.002 in men and p = 0.0003 in women). Diabetes was associated with relatively higher prevalence rates of myocardial infarction (diabetic: nondiabetic prevalence ratio = 3.8 vs. 1.9) and CHD (prevalence ratio = 4.6 vs. 1.8) in women than in men. Prevalence rates of heart disease were lowest in the communities in Arizona; prevalence rates were similar in Oklahoma and South Dakota/North Dakota and were two- to threefold higher than those in Arizona. By logistic regression, prevalent CHD among American Indians was significantly and independently related to age, diabetes, hypertension, albuminuria, percentage of body fat, smoking, high concentrations of plasma insulin, and low concentrations of high density lipoprotein cholesterol. In contrast to reports from other non-Indian populations, diabetes was the strongest risk factor. The lower prevalence of CHD among Indians in Arizona is distinctive in view of their higher rates of diabetes, obesity, hypertension, and albuminuria, but it may be partly related to their low frequency of smoking and their low concentrations of total and low density lipoprotein cholesterol. These findings from the initial Strong Heart Study examination emphasize the importance of diabetes and its associated variables as risk factors for CHD in Native American populations. C1 UNIV OKLAHOMA,HLTH SCI CTR,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK 73190. UNIV OKLAHOMA,DEPT BIOSTAT & EPIDEMIOL,OKLAHOMA CITY,OK 73190. NHLBI,BETHESDA,MD 20892. FITZSIMONS ARMY MED CTR,DENVER,CO. ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD. RP HOWARD, BV (reprint author), MEDLANT RES INST,108 IRVING ST NW,WASHINGTON,DC 20010, USA. FU NHLBI NIH HHS [U01-HL41642, U01HL41652, UL01HL41654] NR 66 TC 171 Z9 171 U1 0 U2 3 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 AUG 1 PY 1995 VL 142 IS 3 BP 254 EP 268 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RM557 UT WOS:A1995RM55700003 PM 7631630 ER PT J AU WELTY, TK LEE, ET YEH, YL COWAN, LD GO, O FABSITZ, RR LEE, NA OOPIK, AJ ROBBINS, DC HOWARD, BV AF WELTY, TK LEE, ET YEH, YL COWAN, LD GO, O FABSITZ, RR LEE, NA OOPIK, AJ ROBBINS, DC HOWARD, BV TI CARDIOVASCULAR-DISEASE RISK-FACTORS AMONG AMERICAN-INDIANS - THE STRONG HEART-STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CARDIOVASCULAR DISEASES; CHOLESTEROL; DIABETES MELLITUS; HYPERTENSION; INDIANS, NORTH AMERICAN; OBESITY; RISK FACTORS; SMOKING ID ACUTE MYOCARDIAL-INFARCTION; PIMA-INDIANS; ALASKA NATIVES; BLOOD-PRESSURE; HYPERTENSION PREVALENCE; CHOLESTEROL LEVELS; DIABETES-MELLITUS; NAVAJO INDIANS; SIOUX INDIANS; MORTALITY AB Strong Heart Study, a study of cardiovascular disease among American Indians, was conducted to determine cardiovascular disease rates and the prevalence of risk factors among members of 13 tribal groups in South Dakota/North Dakota (SD/ND), southeastern Oklahoma, and Arizona. From 1989 to 1992, 4,549 tribal members aged 45-74 years (62% of eligible participants) were surveyed and examined for cardiovascular disease and its risk factors, Mean total cholesterol concentrations were over 20 mg/dl lower among the men and 27 mg/dl lower among the women than national mean levels for the same age groups. Cholesterol levels varied by tribal group; Arizona Indians had mean levels more than 20 mg/dl lower than those of SD/ND Indians. The prevalence of hypercholesterolemia was almost twice as high among SD/ND Indians as among Arizona Indians, but the rates for all three groups were much lower than total US rates (all races). Mean levels of high density lipoprotein cholesterol were lower among Indian men and women than in the US population as a whole. The prevalence of hypertension among Arizona and Oklahoma Indians was higher than that for the entire United States. SD/ND Indians had significantly lower mean blood pressures and prevalence rates of hypertension than Oklahoma and Arizona Indians and the United States as a whole. The prevalence of cigarette smoking was higher for all Indian groups except Arizona women in comparison with US rates. Smoking rates were highest in SD/ND and lowest in Arizona. Indian smokers smoked fewer cigarettes per day than the average US smoker. Arizona Indians had the highest prevalence of diabetes mellitus; over. 60% of those participants were diabetic, In Oklahoma and SD/ND, one third of the men and over 40% of the women were diabetic. In addition, 13-20% of the participants had impaired glucose tolerance. Proteinuria was also a common problem; almost half of the Arizona Indians had micro- or macroalbuminuria, and 20% of Oklahoma and SD/ND Indians had significant proteinuria. The prevalence of obesity was high in all three groups, with Arizona Indians having the highest rates and the highest mean body mass indices, The prevalence of current alcohol use was lower among Indians than in the nation as a whole, but binge drinking was common among those who used alcohol. These results indicate that cardiovascular disease risk factors vary significantly among tribal groups. Prevention programs tailored toward decreasing the prevalence of risk factors are recommended for long-term reduction of cardiovascular disease rates in American Indian communities. C1 UNIV OKLAHOMA,HLTH SCI CTR,COLL PUBL HLTH,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK 73190. ABERDEEN AREA INDIAN HLTH SERV,PROGRAM EPIDEMIOL,RAPID CITY,SD. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. EMORY UNIV,CTR ATHEROSCLEROSIS & LIPID METAB,DEPT MED,ATLANTA,GA 30322. ABERDEEN AREA INDIAN HLTH SERV,DENVER,CO. FITZSIMONS ARMY MED CTR,DENVER,CO. MEDLANT RES INST,WASHINGTON,DC. OI Le, Ngoc-Anh/0000-0002-2634-4798 FU NHLBI NIH HHS [U01HL41652, U01-HL41642, U01HL41654] NR 94 TC 211 Z9 213 U1 1 U2 3 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 AUG 1 PY 1995 VL 142 IS 3 BP 269 EP 287 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RM557 UT WOS:A1995RM55700004 PM 7631631 ER PT J AU DIAMONDSTONE, LS BLAKLEY, SA RICE, JC CLARK, RA GOEDERT, JJ AF DIAMONDSTONE, LS BLAKLEY, SA RICE, JC CLARK, RA GOEDERT, JJ TI PROGNOSTIC FACTORS FOR ALL-CAUSE MORTALITY AMONG HEMOPHILIACS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; FACTOR VIII; HEMOPHILIA; HEPATITIS C VIRUSES; HIV INFECTIONS; MORTALITY ID CD4 LYMPHOCYTE COUNTS; HEPATITIS-B VIRUS; UNITED-STATES; HIV-INFECTION; C VIRUS; AIDS; DEATH; COHORT; RISK; PROGRESSION AB To identify the prognostic significance of hemophilia- and virus-related factors, the authors undertook a survival analysis among 644 human immunodeficiency virus (HIV)-infected subjects enrolled in the Multicenter Hemophilia Cohort Study between 1985 and 1993. Acquired immunodeficiency syndrome (AIDS) was the leading cause of death, followed by hemorrhage and hepatic disease. Adverse prognostic factors included older age and CD4-positive lymphocyte values below 14 percent either at entry (age-adjusted mortality rate ratio (RR) = 6.4, 95% confidence interval (CI) 3.4-12.1) or after entry (time-dependent RR = 4.2, 95% CI 2.6-6.7); indeterminate antibody responses to hepatitis C virus (RR = 3.0, 95% CI 1.8-5.0); and inhibitory antibodies to factor VIII concentrates (RR = 1.8, 95% CI 1.1-3.1), Indeterminate hepatitis C virus status was associated with mortality from hepatic disease but not with AIDS mortality, Factors that were not prognostic included duration of HIV infection, hepatitis B virus infection, and other hemophilia variables, These findings suggest that fatal liver disease among coinfected subjects with an indeterminate hepatitis C virus status is probably related to an insufficient humoral response secondary to HIV immune dysfunction and that the risk of death among HIV-infected subjects is best evaluated with age and duration of low CD4 percentage. C1 TULANE UNIV,SCH PUBL HLTH & TROP MED,DEPT EPIDEMIOL & BIOSTAT,NEW ORLEANS,LA. RP DIAMONDSTONE, LS (reprint author), NATL CANC INST,VIRAL EPIDEMIOL BRANCH,6130 EXECUT BLVD,EPN-434,ROCKVILLE,MD 20852, USA. NR 46 TC 20 Z9 20 U1 1 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 AUG 1 PY 1995 VL 142 IS 3 BP 304 EP 313 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RM557 UT WOS:A1995RM55700007 PM 7631634 ER PT J AU COATES, PM AF COATES, PM TI VERY-LONG-CHAIN ACYL-COA DEHYDROGENASE-DEFICIENCY - MOLECULAR-GENETICS OF A MITOCHONDRIAL-MEMBRANE ENZYME SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID COENZYME-A DEHYDROGENASE; BETA-OXIDATION ENZYMES; RAT-LIVER MITOCHONDRIA; PURIFICATION RP COATES, PM (reprint author), NIDDKD,DIABET PROGRAMS BRANCH,NATCHER BLDG 45,ROOM 5AN-24J,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 15 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 AUG PY 1995 VL 57 IS 2 BP 233 EP 234 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA RL771 UT WOS:A1995RL77100004 PM 7668247 ER PT J AU BLOUIN, JL CHRISTIE, DH GOS, A LYNN, A MORRIS, MA LEDBETTER, DH CHAKRAVARTI, A ANTONARAKIS, SE AF BLOUIN, JL CHRISTIE, DH GOS, A LYNN, A MORRIS, MA LEDBETTER, DH CHAKRAVARTI, A ANTONARAKIS, SE TI A NEW DINUCLEOTIDE REPEAT POLYMORPHISM AT THE TELOMERE OF CHROMOSOME 21Q REVEALS A SIGNIFICANT DIFFERENCE BETWEEN MALE AND FEMALE RATES OF RECOMBINATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DNA POLYMORPHISMS; HUMAN GENOME; REDUCED RECOMBINATION; PARENTAL ORIGIN; TRISOMY-21; SEQUENCE; NONDISJUNCTION; METAPHASE; LINKAGE; MARKERS AB We have used a half-YAC containing the human chromosome 21 long-arm telomere to clone, map, and characterize a new dinucleotide repeat polymorphism (D21S1575) close to 21qter. This marker is <120 kb from the telomeric (TTAGGG)(n) sequences and is the most distal highly polymorphic marker on chromosome 21q. This marker has a heterozygosity of 71% because of a variable (TA), repeat embedded within a long interspersed element (LINE) element. Genotyping of the CEPH families and linkage analysis provided a more accurate determination of the full length of the chromosome 21 genetic map. A highly significant difference was detected between male and female recombination rates in the telomeric region: in the most telomeric 2.3 Mb of chromosome 21q, recombination was only observed in male meioses. C1 CANTONAL HOSP,DIV MED GENET,GENEVA,SWITZERLAND. UNIV GENEVA,SCH MED,DEPT GENET & MICROBIOL,GENES R US LAB HUMAN MOLEC GENET,GENEVA,SWITZERLAND. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH. UNIV HOSP CLEVELAND,CLEVELAND,OH. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. RI Antonarakis, Stylianos/N-8866-2014; Christie, Derek/A-3273-2016 OI Antonarakis, Stylianos/0000-0001-8907-5823; Christie, Derek/0000-0001-7642-0245 NR 35 TC 33 Z9 34 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 AUG PY 1995 VL 57 IS 2 BP 388 EP 394 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA RL771 UT WOS:A1995RL77100022 PM 7668265 ER PT J AU MELTON, T PETERSON, R REDD, AJ SAHA, N SOFRO, ASM MARTINSON, J STONEKING, M AF MELTON, T PETERSON, R REDD, AJ SAHA, N SOFRO, ASM MARTINSON, J STONEKING, M TI POLYNESIAN GENETIC AFFINITIES WITH SOUTHEAST-ASIAN POPULATIONS AS IDENTIFIED BY MTDNA ANALYSIS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN MITOCHONDRIAL-DNA; 9-BP DELETION; GLOBIN GENES; REARRANGEMENTS; POLYMORPHISM; SEQUENCES AB Polynesian generic affinities to populations of Asia were studied using mtDNA markers. A total of 1,037 individuals from 12 populations were screened for a 9-bp deletion in the intergenic region between the COII and tRNA(Lys) genes that approaches fixation in Polynesians. Sequence-specific oligonucleotide probes that identify specific mtDNA control region nucleotide substitutions were used to describe variation in individuals with the 9-bp deletion. The 9-bp deletion was not observed in northern Indians, Bangladeshis, or Pakistanis but was seen at low to moderate frequencies in the nine other Southeast Asian populations. Three substitutions in the control region at positions 16217, 16247, and 16261 have previously been observed at high frequency in Polynesian mtDNAs; this ''Polynesian motif'' was observed in 20% of east Indonesians with the 9-bp deletion but was observed in only one additional individual, mtDNA types related to the Polynesian motif are highest in frequency in the corridor from Taiwan south through the Philippines and east Indonesia, and the highest diversity for these types is in Taiwan. These results are consistent with linguistic evidence of a Taiwanese origin for the proto-Polynesian expansion, which spread throughout Oceania by way of Indonesia. C1 NIAAA,NEUROGENET LAB,BETHESDA,MD. NATL UNIV SINGAPORE HOSP,DEPT PEDIAT,SINGAPORE,SINGAPORE. GAGJAH MADA UNIV,IUC BIOTECHNOL,YPGYAKARTA,INDONESIA. GAGJAH MADA UNIV,FAC MED,YPGYAKARTA,INDONESIA. UNIV OXFORD,INST MOLEC MED,OXFORD,ENGLAND. RP MELTON, T (reprint author), PENN STATE UNIV,DEPT ANTHROPOL,UNIVERSITY PK,PA 16802, USA. NR 37 TC 176 Z9 184 U1 0 U2 4 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 AUG PY 1995 VL 57 IS 2 BP 403 EP 414 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA RL771 UT WOS:A1995RL77100024 PM 7668267 ER PT J AU RUSSELL, MW DICK, M CAMPBELL, RM HULSE, JE MUNROE, DJ BRIC, E HOUSMAN, DE COLLINS, FS BRODY, LC AF RUSSELL, MW DICK, M CAMPBELL, RM HULSE, JE MUNROE, DJ BRIC, E HOUSMAN, DE COLLINS, FS BRODY, LC TI LOCALIZATION OF ROMANO-WARD LONG QT SYNDROME GENE, LQT1, TO THE INTERVAL BETWEEN TYROSINE-HYDROXYLASE (TH) AND D11S1349 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID POLYMORPHISM; LINKAGE C1 UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. EMORY UNIV,EGLESTON CHILDRENS HOSP,CHILDRENS HEART CTR,ATLANTA,GA. MIT,DEPT BIOL,CAMBRIDGE,MA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. RP RUSSELL, MW (reprint author), UNIV MICHIGAN,DEPT PEDIAT & COMMUNICABLE DIS,ANN ARBOR,MI 48109, USA. NR 20 TC 5 Z9 6 U1 0 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 AUG PY 1995 VL 57 IS 2 BP 503 EP 507 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA RL771 UT WOS:A1995RL77100034 PM 7668277 ER PT J AU DEMERS, PA KOGEVINAS, M BOFFETTA, P LECLERC, A LUCE, D GERIN, M BATTISTA, G BELLI, S BOLMAUDORF, U BRINTON, LA COLIN, D COMBA, P HARDELL, L HAYES, RB MAGNANI, C MERLER, E MORCET, JF PRESTONMARTIN, S MATOS, E RODELLA, S VAUGHAN, TL ZHENG, W VAINIO, H AF DEMERS, PA KOGEVINAS, M BOFFETTA, P LECLERC, A LUCE, D GERIN, M BATTISTA, G BELLI, S BOLMAUDORF, U BRINTON, LA COLIN, D COMBA, P HARDELL, L HAYES, RB MAGNANI, C MERLER, E MORCET, JF PRESTONMARTIN, S MATOS, E RODELLA, S VAUGHAN, TL ZHENG, W VAINIO, H TI WOOD DUST AND SINONASAL CANCER - POOLED REANALYSIS OF 12 CASE-CONTROL STUDIES SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE SINONASAL CANCER; ADENOCARCINOMA; WOOD DUST; WOOD-RELATED INDUSTRIES; WOOD-RELATED OCCUPATIONS ID SQUAMOUS-CELL CANCERS; SINONASAL CANCER; PARANASAL SINUSES; RISK-FACTORS; OCCUPATIONAL EXPOSURES; MAXILLARY SINUS; LEATHER DUST; CAVITY; NOSE; FORMALDEHYDE AB In order to examine the relationship between wood dust and sine-nasal cancer, data from 12 case-control studies conducted in seven countries were pooled and reanalyzed. The relative risks associated with wood-related jobs and with exposure to wood dust, measured using a job exposure matrix based on occupation and industry titles, were examined using logistic regression. The combined data set consisted of 680 male cases, 2,349 male controls, 250 female cases, and 787 female controls. A high risk of adenocarcinoma among men was associated with employment in wood-related occupations (odds ratio [OR] = 13.5, 95% confidence interval [CI] = 9.0-20.0) and the risk was greatest among men who had been employed in jobs with the highest wood dust exposure (OR = 45.5, 95% CI = 28.3-72.9) and increased with duration of exposure. The risk of adenocarcinoma also appeared elevated among women employed in wood-related jobs (OR = 2.5, 95% CI = 0.5-12.3), but the small number of exposed cases precluded detailed analysis. Women in wood dust-exposed jobs appeared to have an excess of squamous cell carcinoma (OR = 2.1, 95% CI = 0.8-5.5) which increased with duration of exposure, An increased risk of squamous cell carcinoma in men was seen only among those employed for 30 or more years in jobs with exposure to fresh wood (OR = 2.4, 95% CI = 1.1-5.0). The results of this analysis provide strong support to the association between exposure to wood dust in a variety of occupations and the risk of sine-nasal adenocarcinoma and are consistent with the results of individual participating studies, although the magnitude of the excess risk varied. The evidence in regard to squamous cell carcinomas was ambiguous and there was a great deal of heterogeneity observed in individual study results. This may be due to differences in risk associated with exposure to hardwoods and softwoods or with other, as yet to be identified, aspects of exposure. (C) 1995 Wiley-Liss, Inc. C1 INT AGCY RES CANC,F-69372 LYON,FRANCE. INSERM,PARIS,FRANCE. UNIV MONTREAL,MONTREAL,PQ,CANADA. UNIV SIENA,I-53100 SIENA,ITALY. INST SUPER SANITA,ROME,ITALY. HESS MINIST FRAUEN ARBEIT & SOZIALORDNUNG,WIESBADEN,GERMANY. NCI,BETHESDA,MD 20892. OREBRO MED CTR HOSP,OREBRO,SWEDEN. UNIV TURIN,TURIN,ITALY. CTR STUDIO & PREVENZ ONCOL,I-50131 FLORENCE,ITALY. UNIV SO CALIF,LOS ANGELES,CA. INST ONCOL ANGEL H ROFFO,BUENOS AIRES,DF,ARGENTINA. UNIV VERONA,VERONA,ITALY. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. INST OCCUPAT HLTH,HELSINKI,FINLAND. RP DEMERS, PA (reprint author), UNIV BRITISH COLUMBIA,OCCUPAT HYG PROGRAMME,2206 E MALL,3RD FLOOR,VANCOUVER,BC V6T 1Z3,CANADA. RI Brinton, Louise/G-7486-2015; LUCE, Daniele/J-9125-2015; Kogevinas, Manolis/C-3918-2017 OI Brinton, Louise/0000-0003-3853-8562; NR 36 TC 72 Z9 72 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 1995 VL 28 IS 2 BP 151 EP 166 DI 10.1002/ajim.4700280202 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RL996 UT WOS:A1995RL99600001 PM 8585514 ER PT J AU WALSH, TJ MERZ, WG LEE, JW SCHAUFELE, R SEIN, T WHITCOMB, PO RUDDEL, M BURNS, W WINGARD, JR SWITCHENKO, AC GOODMAN, T PIZZO, PA AF WALSH, TJ MERZ, WG LEE, JW SCHAUFELE, R SEIN, T WHITCOMB, PO RUDDEL, M BURNS, W WINGARD, JR SWITCHENKO, AC GOODMAN, T PIZZO, PA TI DIAGNOSIS AND THERAPEUTIC MONITORING OF INVASIVE CANDIDIASIS BY RAPID ENZYMATIC DETECTION OF SERUM D-ARABINITOL SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID GAS-CHROMATOGRAPHY; CANCER-PATIENTS; AMPHOTERICIN-B; METABOLITE; GRANULOCYTOPENIA; QUANTIFICATION; FUNGEMIA AB BACKGROUND: Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis. PATIENTS AND METHODS: A total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups. RESULTS: A DA/Cr of greater than or equal to 4.0 mu mol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures leg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P <0.01). CONCLUSIONS: Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT LAB MED,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. EMORY UNIV,SCH MED,ATLANTA,GA 30322. SYVA CO,PALO ALTO,CA. RP WALSH, TJ (reprint author), NCI,INFECT DIS SECT,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA. NR 27 TC 56 Z9 59 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 1995 VL 99 IS 2 BP 164 EP 172 DI 10.1016/S0002-9343(99)80136-3 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA RN319 UT WOS:A1995RN31900009 PM 7625421 ER PT J AU BARRETT, RJ HARLAN, LC WESLEY, MN HILL, HA CHEN, VW CLAYTON, LA KOTZ, HL ELEY, W ROBBOY, SJ EDWARDS, BK AF BARRETT, RJ HARLAN, LC WESLEY, MN HILL, HA CHEN, VW CLAYTON, LA KOTZ, HL ELEY, W ROBBOY, SJ EDWARDS, BK TI ENDOMETRIAL CANCER - STAGE AT DIAGNOSIS AND ASSOCIATED FACTORS IN BLACK-AND-WHITE PATIENTS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the South-Atlantic-Association-of-Obstetricians-and-Gynecologists CY JAN 28-31, 1995 CL HOT SPRINGS, VA SP S Atlantic Assoc Obstetricians & Gynecologists DE ENDOMETRIAL CANCER; STAGE; RISK FACTORS; RACE ID RACIAL-DIFFERENCES; RISK-FACTORS; CARCINOMA; SURVIVAL; ADENOCARCINOMA; SUBTYPES; WOMEN AB OBJECTIVE: This study examined the relationship of clinicopathologic, health status, medical system, and socioeconomic factors to differences in stage at diagnosis of endometrial cancer in black and white patients. STUDY DESIGN: A population-based study of 130 black and 329 white patients with invasive endometrial cancer was conducted as part of the National Cancer Institute's Black/White Cancer Survival Study. Logistic regression was used to determine the relative importance of factors thought to be related to stage at diagnosis after age and geographic location were adjusted for. RESULTS: High-grade (poorly differentiated) lesions increased the risk for stage III or IV disease (odds ratio 8.3, 95% confidence interval 3.4 to 20.3), as did serous histologic subtype (odds ratio 3.5, 95% confidence interval 1.4 to 8.8) and no usual source of care (odds ratio 5.5, 95% confidence interval 1.4 to 20.9). In the final statistical model these three factors also accounted for the majority of the excess risk of advanced stage for blacks. CONCLUSION: Black-white racial disparities in stage at diagnosis appear to be related to higher-grade lesions and more aggressive histologic subtypes occurring more frequently in black patients with endometrial cancer. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,DURHAM,NC. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,ATLANTA,GA. LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,SHREVEPORT,LA. NEW YORK CITY HLTH & HOSP CORP,NEW YORK,NY. GEORGE WASHINGTON UNIV HOSP,DEPT OBSTET & GYNECOL,WASHINGTON,DC. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. NR 26 TC 37 Z9 37 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1995 VL 173 IS 2 BP 414 EP 423 DI 10.1016/0002-9378(95)90261-9 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RR029 UT WOS:A1995RR02900010 PM 7645616 ER PT J AU MINKOFF, H BURNS, DN LANDESMAN, S YOUCHAH, J GOEDERT, JJ NUGENT, PP MUENZ, LR WILLOUGHBY, AD AF MINKOFF, H BURNS, DN LANDESMAN, S YOUCHAH, J GOEDERT, JJ NUGENT, PP MUENZ, LR WILLOUGHBY, AD TI THE RELATIONSHIP OF THE DURATION OF RUPTURED MEMBRANES TO VERTICAL TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; RUPTURE OF MEMBRANES; VIRUS TRANSMISSION ID IGA HIV ANTIBODIES; EARLY DIAGNOSIS; INFECTION; WOMEN; INFANTS; RISK AB OBJECTIVE: Intrapartum events may play a role in determining the likelihood of vertical transmission of human immunodeficiency virus-1. Timing and duration of rupture of membranes have been shown to modify transmission risk of other organisms but have not been examined for human immunodeficiency virus. This study was undertaken to assess the relationship between duration of rupture of membranes, maternal immune status, and transmission of human immunodeficiency virus. METHODS: The Mothers' and Infants' Cohort Study enrolled 207 human immunodeficiency virus-positive women and their infants at five study sites in Brooklyn and the Bronx, New York between January 1986 and January 1991. One hundred twenty-seven woman-infant sets for whom antepartum CD4(+) levels were available, the infant's human immunodeficiency virus infection outcome was known, and the duration of ruptured membranes could be determined were included in this analysis. RESULTS: Thirty of the 127 evaluable infants (24%) were infected. Women with low CD4(+) levels (< 20%) were significantly more likely to transmit the virus if rupture of membranes was greater than or equal to 4 hours (relative risk 4.53, 95% confidence interval 1.14 to 1.81, p = 0.02). The same association was not observed among women with higher CD4(+) levels (relative risk 1.11, 95% confidence interval 0.52 to 2.69, p = 0.69). No association with the duration of labor or mode of delivery was seen. CONCLUSIONS: In this urban North American cohort women with low CD4(+) levels were significantly more likely to transmit human immunodeficiency virus to their offspring if the duration of rupture of membranes was greater than or equal to 4 hours. C1 SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY 11203. ALBERT EINSTEIN COLL MED,DEPT GYNECOL & OBSTET,BRONX,NY. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD. WESTAT CORP,ROCKVILLE,MD. FU NCI NIH HHS [N0-1-CP-61013]; NICHD NIH HHS [N0-1-HD-82913, R0-1-HD-25714] NR 23 TC 88 Z9 92 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1995 VL 173 IS 2 BP 585 EP 589 DI 10.1016/0002-9378(95)90286-4 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RR029 UT WOS:A1995RR02900035 PM 7645638 ER PT J AU ANDREWS, WW HAUTH, JC GOLDENBERG, RL GOMEZ, R ROMERO, R CASSELL, GH AF ANDREWS, WW HAUTH, JC GOLDENBERG, RL GOMEZ, R ROMERO, R CASSELL, GH TI AMNIOTIC-FLUID INTERLEUKIN-6 - CORRELATION WITH UPPER GENITAL-TRACT MICROBIAL COLONIZATION AND GESTATIONAL-AGE IN WOMEN DELIVERED AFTER SPONTANEOUS LABOR VERSUS INDICATED DELIVERY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE CHORIOAMNION INFECTION; PRETERM LABOR; PREMATURITY; INTERLEUKIN-6; CHORIOAMNIONITIS ID BLOOD-CELL COUNT; PRETERM LABOR; CHORIOAMNION INFECTION; GRAM STAIN; ASSOCIATION; MEMBRANES; GLUCOSE AB OBJECTIVE: Our purpose was to determine whether amniotic fluid interleukin-6 is increased and inversely proportional to gestational age in women with chorioamnion colonization and spontaneous labor versus women delivered for medical or obstetric indications. STUDY DESIGN: The chorioamnion and amniotic fluid were cultured at cesarean delivery for aerobic and anaerobic bacteria, fungi, mycoplasmas, Chlamydia trachomatis and Trichomonas vaginalis in 269 women with singleton gestations with intact membranes. The amniotic fluid interleukin-6 concentration was also determined. RESULTS: Amniotic fluid interleukin-6 levels were (1) higher in women with spontaneous labor versus those with indicated deliveries (15.8 +/- 5.0 vs 2.2 +/- 0.2 ng/ml, p = 0.01), (2) inversely proportional to gestational age in women with spontaneous labor (<34 weeks: 47.4 +/- 18.0 ng/ml vs greater than or equal to 34 weeks: 8.7 +/- 4.1 ng/ml, p = 0.001) but not in women with indicated deliveries (1.5 +/- 0.4 vs 2.4 +/- 0.3 ng/ml), (3) higher in women with a positive versus a negative chorioamnion (15.1 +/- 4.8 vs 3.0 +/- 0.8 ng/ml, p < 0.001) or amniotic fluid (17.4 +/- 7.7 vs 3.8 +/- 0.9 ng/ml, p < 0.001) culture, and (4) higher in women with a negative amniotic fluid but positive chorioamnion culture compared with women in whom both cultures were negative (10.0 +/- 4.4 vs 3.0 +/- 0.9 ng/ml, p = 0.002). CONCLUSIONS: Amniotic fluid interleukin-6 levels are (1) higher and inversely proportional to gestational age in women with intact membranes and spontaneous labor versus indicated deliveries, (2) higher in women with one or more microorganisms in the chorioamnion or amniotic fluid, and (3) reflective of chorioamnion microbial colonization, even when the amniotic fluid culture is negative, and may be a useful clinical marker for infection-mediated preterm labor. C1 UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35233. UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35294. WAYNE STATE UNIV,DEPT OBSTET & GYNECOL,DETROIT,MI. NICHHD,PERINATOL BRANCH,WASHINGTON,DC. FU NICHD NIH HHS [HD 20928] NR 19 TC 161 Z9 167 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1995 VL 173 IS 2 BP 606 EP 612 DI 10.1016/0002-9378(95)90290-2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RR029 UT WOS:A1995RR02900039 PM 7645642 ER PT J AU DONOVAN, MJ MIRANDA, RC KRAEMER, R MCCAFFREY, TA TESSAROLLO, L MAHADEO, D SHARIF, S KAPLAN, DR TSOULFAS, P PARADA, L TORANALLERAND, CD HAJJAR, DP HEMPSTEAD, BL AF DONOVAN, MJ MIRANDA, RC KRAEMER, R MCCAFFREY, TA TESSAROLLO, L MAHADEO, D SHARIF, S KAPLAN, DR TSOULFAS, P PARADA, L TORANALLERAND, CD HAJJAR, DP HEMPSTEAD, BL TI NEUROTROPHIN AND NEUROTROPHIN RECEPTORS IN VASCULAR SMOOTH-MUSCLE CELLS - REGULATION OF EXPRESSION IN RESPONSE TO INJURY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; FACTOR MESSENGER-RNA; FACTOR FAMILY; INSITU HYBRIDIZATION; MOLECULAR-CLONING; RAT TRKC; NEURONS; BRAIN; SYSTEM AB The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons, Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and mt vascular smooth muscle cells in viva In vitro cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BDNF and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. lit human coronary atherosclerotic lesions, BDNF NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role lit regulating the response of vascular smooth muscle cells to injury. C1 CORNELL UNIV,COLL MED,DEPT PATHOL,DIV HEMATOL,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,DEPT MED,NEW YORK,NY 10021. COLUMBIA UNIV,COLL PHYS & SURG,DEPT ANAT & CELL BIOL,NEW YORK,NY. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA. NCI,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. OI Tsoulfas, Pantelis/0000-0003-1974-6366 FU NHLBI NIH HHS [HL42608, HL46403]; NINDS NIH HHS [NS30687] NR 59 TC 208 Z9 210 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1995 VL 147 IS 2 BP 309 EP 324 PG 16 WC Pathology SC Pathology GA RN764 UT WOS:A1995RN76400009 PM 7639328 ER PT J AU ZHANG, K FLANDERS, KC PHAN, SH AF ZHANG, K FLANDERS, KC PHAN, SH TI CELLULAR-LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA EXPRESSION IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; FACTOR-BETA-1; LUNG; FIBRONECTIN; COLLAGEN; HAMSTER; ALPHA; CELLS; MODEL AB Bleomycin-induced pulmonary, fibrosis is associated with increased lung transforming growth factor-beta(TGF-beta) gene expression, but cellular localization of the source of this expression has not been unequivocally, established In this study, lung fibrosis was induced in rats by endotracheal bleomycin injection on day 0 and on selected days afterwards, lungs were harvested for in situ hybridization, immunohistochemical and histochemical analyses for TGF-beta(1) mRNA and protein expression, and cell identification The results show that control lungs express essentially no detectable TGF-beta(1) mRNA or protein in the parenchyma. Before day 3 after bleomycin treatment, scattered bronchiolar epithelial cells, mononuclear cells, and eosinophils expressed elevated levels of TGF-beta(1). Between days 3 and 14, there was a major increase in the number of eosinophils, myofibroblasts, and fibroblasts strongly expressing TGF-beta(1) mRNA and protein. TGF-beta(1)-producing cells were predominantly localized within areas of injury and active fibrosis. After day 14, the intensity and number of TGF-beta(1)-expressing cells significantly declined and were predominantly found in fibroblasts in fibrotic areas, The expression of TGF-beta(1) Protein was generally coincident with that for mRNA with the exception of bronchiolar epithelial cells in which strong protein expression was unaccompanied by a commensurate increase in mRNA. The study demonstrates that myofibroblasts, fibroblasts, and eosinophils represent the major sources of increased lung TGF-beta(1) expression in this model of pulmonary fibrosis. C1 UNIV MICHIGAN,SCH MED,DEPT PATHOL M0602,ANN ARBOR,MI 48109. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RI Phan, Sem/A-7033-2009; OI Phan, Sem/0000-0002-3711-2159 FU NHLBI NIH HHS [HL28737, HL31963, HL46487] NR 30 TC 142 Z9 158 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1995 VL 147 IS 2 BP 352 EP 361 PG 10 WC Pathology SC Pathology GA RN764 UT WOS:A1995RN76400012 PM 7543734 ER PT J AU HOGG, MG EVANS, CH SMITH, TJ AF HOGG, MG EVANS, CH SMITH, TJ TI LEUKOREGULIN INDUCES PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN HUMAN ORBITAL FIBROBLASTS SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE GRAVES OPHTHALMOPATHY; INFLAMMATION; EXTRACELLULAR MATRIX ID HUMAN DERMAL FIBROBLASTS; GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; GENE-EXPRESSION; GLYCOSAMINOGLYCAN SYNTHESIS; TRANSCRIPTIONAL ACTIVATION; ENDOTHELIAL-CELLS; TISSUE; STIMULATION AB Leukoregulin, a 50-kDa T lymphocyte-derived cytokine, influences the synthesis of collagenase, stromelysin-1, collagen, and hyaluronan in human fibroblasts and is thus a determinant of extracellular matrix economy. We studied the effect of leukoregulin on the expression of plasminogen activator inhibitor type 1 (PAI-1) in human orbital and dermal fibroblasts. The lymphokine upregulated S-35-labeled PAI-1 protein expression in orbital fibroblasts in dose-dependent manner. The effect on extracullular matrix-associated PAI-1 evolved over several hours and was maximal at 10 h, when levels were 75-fold higher than controls, and then fell by 24 h. Leukoregulin treatment increased prostaglandin E(2) production in orbital cultures after 24 h. When this increase was blocked with indomethacin, peak PAI-1 levels were maintained. Northern analysis demonstrated a substantial induction of steady-state PAI-1 mRNA levels within 6 h of treatment in orbital cultures. In contrast, leukoregulin lowered PAI-1 protein levels dramatically in skin fibroblasts from the abdominal wall. With regard to PAI-1 expression, it would appear that the anatomic site of origin of fibroblasts is a crucial determinant of the cellular response to leukoregulin. C1 ALBANY MED COLL, SAMUEL S STRATTON VET AFFAIRS MED CTR, DEPT MED, DIV MOLEC & CELLULAR MED A175, ALBANY, NY 12208 USA. ALBANY MED COLL, SAMUEL S STRATTON VET AFFAIRS MED CTR, DEPT BIOCHEM & MOLEC BIOL, ALBANY, NY 12208 USA. NCI, DIV CANC ETIOL, TUMOR BIOL SECT, BETHESDA, MD 20892 USA. FU NEI NIH HHS [EY-08976] NR 33 TC 25 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 1995 VL 269 IS 2 BP C359 EP C366 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RP469 UT WOS:A1995RP46900008 PM 7653518 ER PT J AU BOLUYT, MO LONG, XL ESCHENHAGEN, T MENDE, U SCHMITZ, W CROW, MT LAKATTA, EG AF BOLUYT, MO LONG, XL ESCHENHAGEN, T MENDE, U SCHMITZ, W CROW, MT LAKATTA, EG TI ISOPROTERENOL INFUSION INDUCES ALTERATIONS IN EXPRESSION OF HYPERTROPHY-ASSOCIATED GENES IN RAT-HEART SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE EXTRACELLULAR MATRIX; ATRIAL NATRIURETIC FACTOR; SKELETAL ALPHA-ACTIN; FIBRONECTIN; TRANSFORMING GROWTH FACTOR-BETA; SARCOPLASMIC RETICULUM CALCIUM ADENOSINE-TRIPHOSPHATASE; PREPROENKEPHALIN ID INDUCED CARDIAC-HYPERTROPHY; MESSENGER-RNA; ALPHA-1-ADRENERGIC RECEPTOR; STIMULATION; GROWTH; ACTIN; BETA; FIBROSIS; COLLAGEN; MUSCLE AB Chronic infusion of isoproterenol (Iso) in rats results in cardiac hypertrophy via incompletely understood mechanisms. Our purpose was to determine whether Iso infusion would alter the expression of genes associated with hypertrophy. Male Wistar rats received either 2.4 mg Iso . kg(-1). day(-1), 9.9 mg propranolol (Prop). kg(-1). day(-1), both Iso and Prop, or vehicle (NaCl) via subcutaneously implanted osmotic pumps. In Iso-treated rats, the ventricular weight-to-body weight ratio was increased by 27% after 1 day and peaked on day 3 (+/-40%). Levels of atrial natriuretic factor (ANF) and fibronectin (FN) mRNA in the left ventricles were elevated 20-fold and 13-fold in Iso-treated rats, respectively, peaking at 3 days of infusion. The increase in FN mRNA accumulation was at least partially accounted for by elevated expression of extra type IIIA and IIIB (EIIIA and EIIIB) splicing variants. Levels of transforming growth factor (TGF)-beta(1) mRNA were elevated twofold after 3 days of Iso infusion. The abundance of skeletal a-actin (SK) mRNA increased fourfold after 1 day of Iso and declined thereafter. Iso infusion decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA) and preproenkephalin (PNK) gene expression by similar to 50% and induced a myosin heavy chain (MHC) isogene switch favoring Rho-MHC. Prop partially inhibited the Iso-evoked increases in ANF and FN mRNA, completely prevented the Iso-induced changes in TGF-beta(1) and SERCA mRNA, but had no effect on the Iso-stimulated changes in SK and PNK gene expression. These results demonstrate that chronic Iso infusion elicits alterations in cardiac gene expression that are consistent with the development of myocyte hypertrophy and interstitial fibrosis and are directionally identical to those previously reported for pressure overload hypertrophy. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. UNIV KRANKENHAUS EPPENDORF, ALLGEMEINE PHARMAKOL ABT, D-20246 HAMBURG, GERMANY. NR 37 TC 105 Z9 113 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1995 VL 269 IS 2 BP H638 EP H647 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA RP467 UT WOS:A1995RP46700028 PM 7653628 ER PT J AU DIENEL, GA TOFELGREHL, B CRUZ, CC LULUDIS, K PETTIGREW, K SOKOLOFF, L GIBSON, GE AF DIENEL, GA TOFELGREHL, B CRUZ, CC LULUDIS, K PETTIGREW, K SOKOLOFF, L GIBSON, GE TI DETERMINATION OF LOCAL-RATES OF CA-45 INFLUX INTO RAT-BRAIN BY QUANTITATIVE AUTORADIOGRAPHY - STUDIES OF AGING SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE CALCIUM; UPTAKE ID CEREBROSPINAL-FLUID CALCIUM; CHRONIC HYPOCALCEMIA; NERVOUS-SYSTEM; AGED RATS; ACCUMULATION; HYPERCALCEMIA; HOMEOSTASIS; PLASMA; SPACE AB Calcium homeostasis in brain is altered in many conditions, but there is no method to assay quantitatively local calcium flux into brain in vivo. Ca-45 uptake into gross-dissected brain regions was measured and compared with results obtained with a quantitative autoradiographic procedure developed to assay influx of Ca-45 into brain. Regional calcium contents, brain-to-plasma distribution ratios for calcium and Ca-45, apparent plasma-to-brain transfer coefficients, and net uptake of Ca-45 into gross-dissected regions varied by as much as 80%. Local rates of net uptake of Ca-45 into 34 structures determined by autoradiography varied by 12- to 14-fold, and rates of movement of Ca-45 down concentrations gradients varied by a factor of 7. Previous studies with gross-dissected brain regions suggested changes in calcium uptake into brain during aging, but the values of all the variables assayed in the present study were similar in young adult, middle-aged, and old male rats. A quantitative autoradiographic procedure to assay levels of Ca-45 in brain provides the anatomical resolution required to investigate local calcium flux in a variety of physiological and pathological conditions. C1 CORNELL UNIV MED COLL, BURKE MED RES INST, DEMENTIA RES PROGRAM, WHITE PLAINS, NY 10605 USA. NIMH, CEREBRAL METAB LAB, BETHESDA, MD 20892 USA. NIMH, DIV EPIDEMIOL & SERV RES, BETHESDA, MD 20892 USA. RI Cruz, Celia/K-3977-2013 OI Cruz, Celia/0000-0001-8922-5713 FU NIA NIH HHS [R01-AG-04171]; NIMH NIH HHS [MH-48325-01A1] NR 30 TC 2 Z9 2 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD AUG PY 1995 VL 269 IS 2 BP R453 EP R462 PG 10 WC Physiology SC Physiology GA RP466 UT WOS:A1995RP46600030 PM 7653670 ER PT J AU MILLER, DS AF MILLER, DS TI DAUNOMYCIN SECRETION BY KILLIFISH RENAL PROXIMAL TUBULES SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE CYCLOSPORINE A; FLUORESCENCE MICROSCOPY; MULTIDRUG-RESISTANCE TRANSPORTER; ORGANIC CATION TRANSPORT SYSTEM; TELEOST FISH; TETRAETHYLAMMONIUM; VIDEO IMAGE ANALYSIS ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN; CYCLOSPORINE-A; ORGANIC ANION; BRUSH-BORDER; TRANSPORT; KIDNEY; MECHANISMS; PRODUCT; DRUGS AB Epifluorescence microscopy and video-image analysis were used to measure the uptake of the fluorescent anthracycline daunomycin by intact killifish renal proximal tubules. When tubules were incubated in medium containing 2-5 mu M daunomycin, the drug accumulated in the cells and the tubular lumen. At steady state, luminal fluorescence was two to three times greater than cellular fluorescence. Luminal accumulation of daunomycin was reduced when tubules were exposed to the multidrug-resistance (MDR) transporter modifiers verapamil and cyclosporin A (CSA), but not tetraethylammonium (TEA), a model substrate for the renal organic cation transport system. NaCN and vanadate reduced luminal drug accumulation. In contrast, cellular daunomycin accumulation was not affected by verapamil, CSA, TEA, or vanadate and was only slightly reduced by NaCN. When the pH of the buffer solution was decreased from 8.25 to 7.25, luminal, but not cellular, accumulation of daunomycin was again reduced by CSA; however, TEA now reduced cellular and luminal accumulation. These findings are consistent with daunomycin being actively secreted in killifish proximal tubule by two mechanisms. At pH 8.25, daunomycin crossed the basolateral membrane by simple diffusion and was secreted into the tubular lumen by the MDR transporter. At pH 7.25, daunomycin was transported across the basolateral membrane by simple diffusion and carrier-mediated uptake on the organic cation transporter and was secreted into the lumen by the MDR transporter and the organic cation/H+ exchanger. RP MILLER, DS (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL LAB, INTRACELLULAR REGULAT SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 34 TC 47 Z9 48 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD AUG PY 1995 VL 269 IS 2 BP R370 EP R379 PG 10 WC Physiology SC Physiology GA RP466 UT WOS:A1995RP46600019 PM 7653659 ER PT J AU HE, CJ ZALUPS, RK HENDERSON, DA STRIKER, GE STRIKER, LJ AF HE, CJ ZALUPS, RK HENDERSON, DA STRIKER, GE STRIKER, LJ TI MOLECULAR ANALYSIS OF SPONTANEOUS GLOMERULOSCLEROSIS IN OS/+ MICE, A MODEL WITH REDUCED NEPHRON MASS SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE CONGENITAL; OLIGONEPHRONIA; GLOMERULAR EXTRACELLULAR MATRIX MESSENGER RIBONUCLEIC ACIDS ID MESANGIAL CELL-PROLIFERATION; COMPENSATORY RENAL GROWTH; GLOMERULAR HYPERTROPHY; EXTRACELLULAR-MATRIX; DIABETIC NEPHROPATHY; TRANSGENIC MICE; REMNANT KIDNEY; SCLEROSIS; RATS; AGE AB Oligosyndactyly mice (ROP Os/+) are a radiation-induced mutant strain with reduced glomerular number and increased glomerular size. We found that they develop glomerulosclerosis. At 3 mo, ROP Os/+ mice had diffuse mesangial expansion by light microscopy, whereas their +/+ littermates did not. Electron microscopic morphometry revealed a twofold increase in mesangial areas but no changes in the thickness of glomerular basal laminae. Mean glomerular volume was increased 1.8-fold. Cell number and thymidine labeling index were increased 1.3- and 2.4-fold, respectively. The amount of glomerular type IV collagen and tenascin but not laminin was increased by immunofluorescence microscopy. mRNA levels in microdissected glomeruli were measured by competitive reverse transcription-polymerase chain reaction and corrected for cell number. alpha(1)-Chain type IV collagen and tenascin mRNAs were increased 3.2-fold and 1.8-fold, whereas laminin B1 mRNA levels were not. The levels of 72-kDa collagenase rnRNA were increased 1.6-fold. Transforming growth factor-beta 1 mRNA levels were elevated 1.8 fold, but platelet-derived growth factor-beta 1 mRNA levels remained normal. This is the first analysis of glomerular molecular and cellular changes in a model of congenital nephron reduction. C1 NIDDK, METAB DIS BRANCH, RENAL CELL BIOL SECT, BETHESDA, MD 20892 USA. MERCER UNIV, SCH MED, DIV BASIC MED SCI, MACON, GA 31207 USA. OKLAHOMA STATE UNIV, COLL OSTEOPATH MED, DEPT RES, TULSA, OK 74107 USA. FU NIEHS NIH HHS [ES-05157] NR 33 TC 39 Z9 39 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD AUG PY 1995 VL 269 IS 2 BP F266 EP F273 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA RP344 UT WOS:A1995RP34400015 PM 7544540 ER PT J AU CORYELL, W ENDICOTT, J WINOKUR, G AKISKAL, H SOLOMON, D LEON, A MUELLER, T SHEA, T AF CORYELL, W ENDICOTT, J WINOKUR, G AKISKAL, H SOLOMON, D LEON, A MUELLER, T SHEA, T TI CHARACTERISTICS AND SIGNIFICANCE OF UNTREATED MAJOR DEPRESSIVE DISORDER SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POPULATION; COMMUNITY; DOCTOR; SAMPLE AB Objective: This study sought to describe the characteristics and consequences of untreated major depressive disorder. Method: As part of a family study of probands with major affective disorders, raters assessed 3,119 first-degree relatives, spouses, and comparison subjects. When 2,237 (71.7%) of these individuals were reassessed 6 years later, 547 had experienced episodes of major depressive disorder in the interval. Those who had sought any form of treatment for any episode of major depressive disorder in the interval were compared, by baseline demographic characteristics and clinical features of their worst episodes of major depressive disorder, to those who had not. Individuals who had had untreated major depressive disorder were then compared, by changes in socioeconomic status and by levels of psychosocial impairment at follow-up, to a matched group with no major depressive disorder in the interval. Results: The worst episodes of 313 treated individuals, compared to those of 234 untreated individuals, were characterized by older age, symptoms of the endogenous subtype, longer durations, and the presence of disruption in role function. Each of these factors contributed independently to she distinction between treated and untreated episodes. Untreated individuals experienced significant psychosocial impairment on follow-up but did not show the economic disadvantages shown elsewhere for probands who began follow-up as they sought treatment at tertiary medical centers. Conclusions: These data suggest that illness characteristics and age determine the decision to seek treatment for major depressive disorder. Untreated depression is apparently associated with long-standing psychosocial difficulties but not with serious economic consequences. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD 20892. NR 16 TC 55 Z9 55 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1995 VL 152 IS 8 BP 1124 EP 1129 PG 6 WC Psychiatry SC Psychiatry GA RL642 UT WOS:A1995RL64200004 PM 7625458 ER PT J AU ALTSHULER, LL POST, RM LEVERICH, GS MIKALAUSKAS, K ROSOFF, A ACKERMAN, L AF ALTSHULER, LL POST, RM LEVERICH, GS MIKALAUSKAS, K ROSOFF, A ACKERMAN, L TI ANTIDEPRESSANT-INDUCED MANIA AND CYCLE ACCELERATION - A CONTROVERSY REVISITED SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIPOLAR AFFECTIVE-DISORDERS; RECURRENT DEPRESSION; LITHIUM-CARBONATE; DOUBLE-BLIND; AFFECTIVE-ILLNESS; ANTI-DEPRESSANTS; TRICYCLIC ANTIDEPRESSANTS; MAINTENANCE THERAPIES; CONTINUATION THERAPY; CONTROLLED TRIAL AB Objective: The longitudinal course of 51 patients with treatment-refractory bipolar disorder was examined to assess possible effects of heterocyclic antidepressants on occurrence of manic episodes and cycle acceleration. Method: Using criteria established from life charts, investigators rated the patients' episodes of mania or cycle acceleration as likely or unlikely to have been induced by antidepressant therapy. Discriminant functions analyses were performed to assess predictors of vulnerability to antidepressant-induced mania or cycle acceleration. Further, the likelihood of future antidepressant-induced episodes in persons who had had one such episode was assessed. Results: Thirty-five percent of the patients had a manic episode rated as likely to have been antidepressant-induced. No variable was a predictor of vulnerability to antidepressant-induced mania. Cycle acceleration was likely to be associated with antidepressant treatment in 26% of the patients assessed. Younger age at first treatment was a predictor of vulnerability to antidepressant-induced cycle acceleration. Forty-six percent of patients with antidepressant-induced mania, but only 14% of those without, also showed antidepressant-induced cycle acceleration at some point in their illness. Conclusions: Mania is likely to be antidepressant-induced and not attributable to the expected course of illness in one-third of treatment-refractory bipolar patients, and rapid cycling is induced in one-fourth. Antidepressant-induced mania may be a marker for increased vulnerability to antidepressant-induced cycle acceleration. Antidepressant-induced cycle acceleration (but not antidepressant-induced mania) is associated with younger age at first treatment and may be more likely to occur in women and in bipolar II patients. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. VET ADM MED CTR BRENTWOOD,LOS ANGELES,CA 90073. NR 90 TC 451 Z9 467 U1 2 U2 10 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1995 VL 152 IS 8 BP 1130 EP 1138 PG 9 WC Psychiatry SC Psychiatry GA RL642 UT WOS:A1995RL64200005 PM 7625459 ER PT J AU ALTSHULER, LL CURRAN, JG HAUSER, P MINTZ, J DENICOFF, K POST, R AF ALTSHULER, LL CURRAN, JG HAUSER, P MINTZ, J DENICOFF, K POST, R TI T-2 HYPERINTENSITIES IN BIPOLAR DISORDER - MAGNETIC-RESONANCE-IMAGING COMPARISON AND LITERATURE METAANALYSIS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID WHITE-MATTER LESIONS; SUBCORTICAL SIGNAL HYPERINTENSITIES; ELDERLY SUBJECTS; MAJOR DEPRESSION; BRAIN; LEUKOENCEPHALOPATHY; MRI; ABNORMALITIES; CRITERIA; FOCI AB Objective: Accumulating evidence suggests a greater number of T-2 abnormalities in the brains of patients with bipolar I disorder. The authors sought to evaluate the presence of signal ''hyperintensities'' in both bipolar I and II subjects and systematically review the existing literature. Method: Magnetic resonance images of the brain were obtained prospectively for 29 patients with bipolar I disorder, 26 patients with bipolar II disorder, and 20 normal comparison subjects. The presence and location of signal hyperintensities in three brain regions (periventricular white matter, subcortical gray matter, and deep white matter) were evaluated. Results: No significant differences were found between groups for the presence of subcortical gray or deep white matter hyperintensities. Periventricular hyperintensities were more common in bipolar I patients (62%) than in bipolar II patients (38%) and normal comparison subjects (30%). Within patient groups, medication use was not significantly different for those with or without the presence of white matter hyperintensities. The literature on bipolar disorder and signal hyperintensities is reviewed. A meta-analysis of the pooled data in the literature on bipolar illness and signal hyperintensities revealed that the odds of having a T-2 hyperintensity are significantly greater for bipolar I than for normal comparison subjects. Conclusions: Having bipolar I disorder significantly increases the chance of having white matter changes in the brain. This study suggests that bipolar II patients may be more similar than bipolar I patients to comparison subjects on T-2 measures. The possible pathophysiological significance of hyperintensities is discussed. C1 UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT RADIOL SCI,LOS ANGELES,CA 90024. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 38 TC 159 Z9 161 U1 1 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1995 VL 152 IS 8 BP 1139 EP 1144 PG 6 WC Psychiatry SC Psychiatry GA RL642 UT WOS:A1995RL64200006 PM 7625460 ER PT J AU TEICHER, MH GLOD, CA OREN, DA SCHWARTZ, PJ LUETKE, C BROWN, C ROSENTHAL, NE AF TEICHER, MH GLOD, CA OREN, DA SCHWARTZ, PJ LUETKE, C BROWN, C ROSENTHAL, NE TI THE PHOTOTHERAPY LIGHT VISOR - MORE TO IT THAN MEETS THE EYE SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; DEPRESSION; THERAPY; MULTICENTER; EFFICACY AB Objective: The purpose of the study was to ascertain whether phototherapy light visors provide an effective treatment for seasonal affective disorder. Previous studies have demonstrated a moderate response rate but have failed to find any difference in efficacy between light intensities. Method: Subjects were randomly assigned to receive, over a 2-week treatment period, 30 minutes of morning phototherapy with a light visor that emitted either a dim (30-lux) red light or a bright (600-lux) white light. Raters were blind to treatment, and patients were unaware of the alternatives. Response was assessed by using the structured 21-item Hamilton Depression Rating Scale, with an eight-item addendum for atypical depressive symptoms. Fifty-seven patients were enrolled across two sites. Results: Patients assigned to the different visors had similar baseline depression scores and similar expectations of outcome. Hamilton depression scale scores declined by 34.6% for subjects given bright white light and by 40.9% for subjects given dim red light. Scores for atypical depressive symptoms fell by 44.1% for patients assigned the bright white light visors and by 43.0% for patients assigned the dim red light visors. Altogether, 39.3% of the patients who received red light and 41.4% of the patients who received bright white light showed a full clinical response. Conclusions: There were no significant differences in therapeutic response between patients who were treated with red or white light. The results of this study suggest that the phototherapy light visor may function as an elaborate placebo. Alternative explanations, however, are considered. C1 MCLEAN HOSP,CLIN CHRONOBIOL LAB,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. RP TEICHER, MH (reprint author), MCLEAN HOSP,DEV BIOPSYCHIAT PROGRAM,115 MILL ST,BELMONT,MA 02178, USA. FU NIMH NIH HHS [MH-48343] NR 21 TC 23 Z9 23 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1995 VL 152 IS 8 BP 1197 EP 1202 PG 6 WC Psychiatry SC Psychiatry GA RL642 UT WOS:A1995RL64200016 PM 7625470 ER PT J AU OZAKI, N ONO, Y ITO, A ROSENTHAL, NE AF OZAKI, N ONO, Y ITO, A ROSENTHAL, NE TI PREVALENCE OF SEASONAL DIFFICULTIES IN MOOD AND BEHAVIOR AMONG JAPANESE CIVIL-SERVANTS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID AFFECTIVE-DISORDER AB Objective: Most prevalence studies of seasonal changes in mood and behavior have come from Western countries. The authors' goal was to determine the prevalence of seasonal changes in mood and behavior in a randomly selected group of Japanese workers. Method: They administered a Japanese translation of the Seasonal Pattern Assessment Questionnaire to 1,276 civil servants in Nagoya, Japan. Results: The estimated prevalence of winter seasonal affective disorder was 0.86%, the estimated Prevalence of winter subsyndromal seasonal affective disorder was 0.86%, the estimated prevalence of summer seasonal affective disorder was 0.94%, and the estimated prevalence of summer subsyndromal seasonal affective disorder was 2.12%. Conclusions: The authors conclude that seasonal changes in mood and behavior occur in Japan, but at a lower frequency and with a different profile than in the United States or Europe. C1 NAGOYA UNIV,SCH MED,DEPT HYG,NAGOYA,AICHI 466,JAPAN. FUJITA HLTH UNIV,SCH MED,DEPT PSYCHIAT,TOYOAKE,AICHI 47011,JAPAN. RP OZAKI, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,RM 4S-239,10 CTR CR,MSC 1390,BETHESDA,MD 20892, USA. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 8 TC 50 Z9 50 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1995 VL 152 IS 8 BP 1225 EP 1227 PG 3 WC Psychiatry SC Psychiatry GA RL642 UT WOS:A1995RL64200025 PM 7625479 ER PT J AU HOUN, F BOBER, MA HUERTA, EE HURSTING, SD LEMON, S WEED, DL AF HOUN, F BOBER, MA HUERTA, EE HURSTING, SD LEMON, S WEED, DL TI THE ASSOCIATION BETWEEN ALCOHOL AND BREAST-CANCER - POPULAR PRESS COVERAGE OF RESEARCH SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BEVERAGE CONSUMPTION; PUBLICATION BIAS; RISK; HEALTH; INFORMATION AB Objectives. This study was undertaken to examine popular press reports of the association between alcohol and breast cancer. Methods. Articles from scientific journals and stories from newspapers and magazines published from January 1, 1985, to July 1, 1992, were retrieved from six on-line databases, Lay press stories were analyzed to determine which medical articles were publicized and what information was reported. Results. Fifty-eight scientific articles on the relationship of alcohol and breast cancer were found, and 64 newspaper and 23 magazine stories were retrieved. The press cited 11 studies, 19% of those published during the study period. Three studies were featured in 77% popular press stories. No scientific review articles were reported. Behavioral recommendations were:given to the public in 63% of stories. Conclusions. The vast majority of scientific studies on alcohol-and breast cancer were ignored In press reports. We encourage researchers and the popular press to give the public a broader understanding of public health issues. C1 NCI,DIV CANC CONTROL & PREVENT,EARLY DETECT & COMMUNITY ONCOL PROGRAM,PREVENT ONCOL BRANCH,BETHESDA,MD 20892. NR 45 TC 21 Z9 21 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1995 VL 85 IS 8 BP 1082 EP 1086 DI 10.2105/AJPH.85.8_Pt_1.1082 PN 1 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RN320 UT WOS:A1995RN32000012 PM 7625500 ER PT J AU RAJ, S NAIR, S MASTORAKOS, G NELSON, LM AF RAJ, S NAIR, S MASTORAKOS, G NELSON, LM TI ANAMNESTIC DEVELOPMENT OF LYMPHOCYTIC INFILTRATION IN MURINE EXPERIMENTAL AUTOIMMUNE OOPHORITIS LS PRIMARILY LOCALIZED IN THE STROMA AND THECA SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Fertility-Society CY NOV 05-10, 1994 CL SAN ANTONIO, TX SP Amer Fertil Soc DE OOPHORITIS; STROMA; THECA ID GLUTAMIC-ACID DECARBOXYLASE; PREMATURE OVARIAN FAILURE; THYMECTOMIZED MICE; CELLULAR EVENTS; CELLS; REQUIREMENT; TOLERANCE; DISEASES; AUTOANTIGEN; MECHANISM AB PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces autoimmune oophoritis and ovarian failure in B6A mice. These mice develop high-titer autoantibodies specific to oocytes, and ultimately the ovaries become fibrotic and devoid of primordial follicles. These findings implicate the oocyte as a primary target of the autoimmune process. However, in previous work we demonstrated that in developing disease the lymphocytic infiltration was confined to the stroma and theca, and not found involving oocytes. Here, we investigate the possibility that lymphocytic infiltration involving oocytes develops as part of end-stage disease. METHOD: We transplanted normal syngeneic ovaries to :B6A mice with confirmed autoimmune ovarian failure, and, as a control, to normal oophorectomized mice. We then defined the time course and histologic distribution of lymphocytic infiltration in the transplanted ovaries. Lymphocytes were identified by morphology with the aid of an immunohistochemical leukocyte marker (CD45). RESULTS: Autoimmune oophoritis developed by 7 days after transplantation to the NTX3 mice. Compared to control mice, in these mice we found significantly increased stromal and thecal lymphocytic infiltration. In no case did we observe lymphocytic infiltration involving oocytes. CONCLUSIONS: Our findings agree with our previous report and suggest that the ovarian failure in this model is not mediated by a direct lymphocytic attack against intact oocytes. Other immune-mediated mechanisms are responsible. The paradoxical development of high-titer oocyte-specific antibodies despite the stromal and thecal location of the lymphocytic infiltration remains to be explained. C1 NICHHD,DEV ENDOCRINOL BRANCH,GYNECOL RES SECT,BETHESDA,MD 20892. LOUISIANA STATE UNIV,MED CTR,DEPT OBSTET & GYNECOL,NEW ORLEANS,LA 70112. NICHHD,DEV ENDOCRINOL BRANCH,PEDIAT ENDOCRINOL SECT,BETHESDA,MD 20892. NR 23 TC 3 Z9 3 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD AUG PY 1995 VL 34 IS 2 BP 125 EP 131 PG 7 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA RU498 UT WOS:A1995RU49800009 PM 8526989 ER PT J AU NAIR, S MASTORAKOS, G RAJ, S NELSON, LM AF NAIR, S MASTORAKOS, G RAJ, S NELSON, LM TI MURINE EXPERIMENTAL AUTOIMMUNE OOPHORITIS DEVELOPS INDEPENDENTLY OF GONADOTROPIN STIMULATION AND IS PRIMARILY LOCALIZED IN THE STROMA AND THECA SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Fertility-Society CY NOV 05-10, 1994 CL SAN ANTONIO, TX SP Amer Fertil Soc DE AUTOIMMUNE OOPHORITIS; GONADOTROPIN; STROMA; THECA ID PREMATURE OVARIAN FAILURE; GLUTAMIC-ACID DECARBOXYLASE; MICE AB PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces experimental autoimmune oophoritis in certain strains of mice. The disease has its onset around the time of the first estrous, suggesting the process may be gonadotropin dependent. Furthermore, one study reported that gonadotropin stimulation exacerbated the ovarian lymphocytic infiltration in NTX3 mice. Here we examine the possibility that gonadotropin ii stimulation of the ovary plays a role in the development of post-thymectomy autoimmune oophoritis. METHOD: Using immunohistochemistry we defined the time course and histologic distribution of the post-thymectomy ovarian lymphocytic infiltration that develops in B6A mice ([C57BL6 X A/J]F-I). We detected ovarian leukocytes using a monoclonal antibody against mouse CD45/T200 and counted those positive staining cells that had the morphologic appearance of lymphocytes. We then treated NTX3 mice to determine if gonadotropin stimulation could exacerbate the disease or cause the disease to appear earlier. We also treated NTX3 mice to determine if gonadotropin suppression could reduce the severity of the disease. RESULTS: Ovarian lymphocytic infiltration was observed as early as 3 weeks after thymectomy, and, during the course of the disease, was primarily located in the stroma and theca. Gonadotropin stimulation did nor exacerbate existing disease or induce an earlier onset of severe disease. Furthermore, gonadotropin suppression did not reduce the degree of lymphocytic infiltration or oocyte destruction. CONCLUSIONS: Our findings suggest that murine experimental autoimmune oophoritis develops independently of gonadotropin stimulation of the ovary. C1 NICHHD,DEV ENDOCRINOL BRANCH,GYNECOL RES SECT,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,PEDIAT ENDOCRINOL SECT,BETHESDA,MD 20892. NR 16 TC 7 Z9 7 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD AUG PY 1995 VL 34 IS 2 BP 132 EP 139 PG 8 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA RU498 UT WOS:A1995RU49800010 PM 8526990 ER PT J AU RAND, CS NIDES, M COWLES, MK WISE, RA CONNETT, J AF RAND, CS NIDES, M COWLES, MK WISE, RA CONNETT, J TI LONG-TERM METERED-DOSE INHALER ADHERENCE IN A CLINICAL-TRIAL SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG HEALTH; EARLY INTERVENTION; ASTHMA; ASSOCIATION; MORTALITY; DESIGN AB Poor adherence to medication regimens is a well-documented phenomenon in clinical practice and an ever-present concern in clinical trials. Little is known about adherence to inhaled medication regimens over extended periods. The present paper describes the 2-yr results of the Lung Health Study (LHS) program, which was developed to maintain long-term adherence to an inhaled medication regimen in 3,923 special intervention participants (as measured by self-report and medication canister weight). The LHS is a double-blind, multicenter, randomized controlled clinical trial of smoking intervention and bronchodilator therapy (ipratropium bromide or placebo) for early intervention in chronic obstructive pulmonary disease (COPD). At the first 4-mo follow-up visit, nearly 70% of participants reported satisfactory or better adherence. Over the next 18 mo, self-reported satisfactory or better adherence declined to about 60%. Canister weight classified adherence as satisfactory or better in 72% of participants returning all canisters at 1 yr, and in 70% of the participants returning all canisters at the 2-yr follow-up. Self-reporting confirmed by canister weight classified 48% of participants at 1 yr as showing satisfactory or better adherence. Overusers were 50% more likely than others to misrepresent their true smoking status, suggesting that canister weights indicating overuse may be deceptive. Results of multiple logistic regression analysis indicate that the best compliance was found in participants who were married, older, white, had more severe airways obstruction, less shortness of breath, and fewer hospitalizations, and who had not been confined to bed for respiratory illnesses. In summary, a structured program for promoting adherence to an inhaled medication regimen was successful in achieving initial satisfactory adherence in the majority of participants; however, adherence declined notably from the conclusion of this program to the first-year follow-up, and more gradually over the second year. C1 JOHNS HOPKINS UNIV,SCH MED,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21218. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV MINNESOTA,DIV BIOSTAT,MINNEAPOLIS,MN 55455. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. HENRY FORD HOSP,DETROIT,MI 48202. MAYO CLIN,ROCHESTER,MN. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV ALABAMA,BIRMINGHAM,AL. UNIV MANITOBA,WINNIPEG,MB R3T 2N2,CANADA. UNIV MINNESOTA,CTR COORDINATING,MINNEAPOLIS,MN 55455. UNIV MIAMI,CORAL GABLES,FL 33124. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV UTAH,SALT LAKE CITY,UT 84112. NHLBI,DIV LUNG DIS,BETHESDA,MD. OI Wise, Robert/0000-0002-8353-2349 FU NHLBI NIH HHS [N01-HR-46016] NR 26 TC 112 Z9 116 U1 1 U2 5 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG PY 1995 VL 152 IS 2 BP 580 EP 588 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RN576 UT WOS:A1995RN57600022 PM 7633711 ER PT J AU KORN, EL GRAUBARD, BI AF KORN, EL GRAUBARD, BI TI EXAMPLES OF DIFFERING WEIGHTED AND UNWEIGHTED ESTIMATES FROM A SAMPLE SURVEY SO AMERICAN STATISTICIAN LA English DT Article DE BIAS; INTERACTION; SAMPLING WEIGHTS; STRATIFICATION ID REGRESSION AB Unweighted estimators using data collected in a sample survey can be badly biased, whereas weighted estimators are approximately unbiased for population parameters. We present four examples using data from the 1988 National Maternal and Infant Health Survey to demonstrate that weighted and unweighted estimators can be quite different, and to show the underlying causes of such differences. C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. RP KORN, EL (reprint author), NCI,BIOMETR RES BRANCH,CLIN TRIALS SECT,BETHESDA,MD 20892, USA. NR 18 TC 110 Z9 111 U1 1 U2 8 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0003-1305 J9 AM STAT JI Am. Stat. PD AUG PY 1995 VL 49 IS 3 BP 291 EP 295 DI 10.2307/2684203 PG 5 WC Statistics & Probability SC Mathematics GA RQ962 UT WOS:A1995RQ96200010 ER PT J AU WAGNER, R KACHAR, B AF WAGNER, R KACHAR, B TI LINEAR GAP AND TIGHT JUNCTIONAL ASSEMBLIES BETWEEN CAPILLARY ENDOTHELIAL-CELLS IN THE EEL RETE-MIRABILE SO ANATOMICAL RECORD LA English DT Article DE ENDOTHELIUM; CAPILLARY; TIGHT JUNCTIONS; GAP JUNCTIONS; CRYOFIXATION; FREEZE-FRACTURE; FREEZE-SUBSTITUTION ID VASCULAR ENDOTHELIUM; PLAKOGLOBIN; MICROSCOPY; PROTEIN; COMMON AB Background: Interendothelial tight junctions and gap junctions have been described in large blood vessels and in cultures of endothelium derived from large blood vessels. Transfer of microinjected small-molecular weight tracers between adjacent endothelial cells also has been demonstrated indicating the presence of gap junctional interendothelial communication, Similar transfer of tracers is evident between microvessel endothelial cells in culture and in microvessels in situ. However, gap junctions have not been detectable by electron microscopy of intact capillary systems. This may be due to limited sampling available in diffuse capillary systems and a small area of overlap between adjacent endothelial membranes. Methods: Thin slices of the parallel, tightly packed capillary bed of the eel rete mirabile were cryofixed and prepared for conventional TEM by freeze-substitution. Other samples were freeze-fractured and replicated for examination of endothelial junctional components. Results: A novel tight-gap junctional complex between rete capillary endothelial cells is described. In freeze-fracture replicas of the membrane P face, rows of gap junction subunits are flanked on either side by Linear depressions representing grooves previously occupied by tight junctional strands that partition to the E face. In thin sections, the junctions appear in profile as short lengths of closely apposed membranes characteristic of gap junctions. Conclusions: The tight junctional components imply a barrier to paracellular transport across the capillary wall between the endothelial cells. The gap junctional component may provide a mechanism for communication between endothelial cells along the length of the vessel wall. (C) 1995 Wiley-Liss, Inc. C1 NIDCD,CELLULAR BIOL LAB,ROCKVILLE,MD. RP WAGNER, R (reprint author), UNIV DELAWARE,DEPT BIOL,NEWARK,DE 19716, USA. NR 17 TC 6 Z9 6 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 0003-276X J9 ANAT REC JI Anat. Rec. PD AUG PY 1995 VL 242 IS 4 BP 545 EP 552 DI 10.1002/ar.1092420410 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA RM011 UT WOS:A1995RM01100009 PM 7486024 ER PT J AU BERGASA, NV ALLING, DW TALBOT, TL SWAIN, MG YURDAYDIN, C TURNER, ML SCHMITT, JM WALKER, EC JONES, EA AF BERGASA, NV ALLING, DW TALBOT, TL SWAIN, MG YURDAYDIN, C TURNER, ML SCHMITT, JM WALKER, EC JONES, EA TI EFFECTS OF NALOXONE INFUSIONS IN PATIENTS WITH THE PRURITUS OF CHOLESTASIS - A DOUBLE-BLIND, RANDOMIZED, CONTROLLED TRIAL SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE NALOXONE; PRURITUS; CHOLESTASIS; NARCOTIC ANTAGONISTS ID PRIMARY BILIARY-CIRRHOSIS; NALMEFENE THERAPY; RAT MODEL; OPIATES; OPIOIDS; STRESS; PLASMA; RELIEF AB Objective: To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. Design: Double-blind, placebo-controlled, crossover trial with four periods. Setting: Clinical research referral center. Patients: 29 pruritic patients with liver diseases of various causes. Intervention: Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. Measurements: During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. Results: One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patients. Conclusions: Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis. C1 NIH,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 36 TC 236 Z9 242 U1 1 U2 2 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 AUG 1 PY 1995 VL 123 IS 3 BP 161 EP 167 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RL104 UT WOS:A1995RL10400001 PM 7598296 ER PT J AU GALLIN, JI FARBER, JM HOLLAND, SM NUTMAN, TB AF GALLIN, JI FARBER, JM HOLLAND, SM NUTMAN, TB TI INTERFERON-GAMMA IN THE MANAGEMENT OF INFECTIOUS-DISEASES SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MYCOBACTERIUM-AVIUM-INTRACELLULARE; SEVERE ATOPIC-DERMATITIS; CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS; PENTAVALENT ANTIMONY; IGE LEVELS; T-CELLS; RECEPTOR; AIDS; RESPONSES AB Interferon-gamma has pleiotropic adjuvant effects on host defenses. These effects have made interferon-gamma particularly useful for enhancing host defenses in patients with chronic granulomatous disease of childhood and thus for reducing the incidence of life-threatening infections in these patients. Increasingly, data suggest that interferon-gamma will be useful for treating infections characterized by intracellular persistence in macrophages, such as toxoplasmosis, leishmaniasis, and mycobacteriosis. Interferon-gamma is emerging as an important cytokine for use in the treatment of infectious diseases. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP GALLIN, JI (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 2C146,10 CTR DR,BETHESDA,MD 20892, USA. NR 63 TC 101 Z9 103 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 AUG 1 PY 1995 VL 123 IS 3 BP 216 EP 224 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA RL104 UT WOS:A1995RL10400009 PM 7598304 ER PT J AU KOVACS, JA AF KOVACS, JA TI TOXOPLASMOSIS IN AIDS - KEEPING THE LID ON SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; MAINTENANCE THERAPY; ENCEPHALITIS; PYRIMETHAMINE; EFFICACY C1 NIH,BETHESDA,MD 20892. NR 20 TC 4 Z9 4 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 AUG 1 PY 1995 VL 123 IS 3 BP 230 EP 231 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RL104 UT WOS:A1995RL10400011 PM 7598306 ER PT J AU ILLA, I ORTIZ, N GALLARD, E JUAREZ, C GRAU, JM DALAKAS, MC AF ILLA, I ORTIZ, N GALLARD, E JUAREZ, C GRAU, JM DALAKAS, MC TI ACUTE AXONAL GUILLAIN-BARRE-SYNDROME WITH IGG ANTIBODIES AGAINST MOTOR AXONS FOLLOWING PARENTERAL GANGLIOSIDES SO ANNALS OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; ANTI-GM1 ANTIBODIES; NEURON DISEASE; GM1 GANGLIOSIDE; M-PROTEIN; POLYNEUROPATHY; GD1B; NEUROPATHY; PATIENT; ASSOCIATION AB We studied 7 patients with an acute motor axonal Guillain-Barre syndrome (GBS), manifested 5 to 15 days after parenteral injection of a commercial ganglioside preparation given for nonspecific pain syndromes. The serum IgG and IgM antibody response to ganglioside was studied serially and the recognition of epitopes on the peripheral nerves and motor end-plates was examined using biotinylated IgG extracted from the patient's serum. Sera from 8 patients treated with the same ganglioside preparation who did not develop neuropathy and from 25 patients with classic GBS never treated with gangliosides were studied concurrently. All patients with ganglioside-related GBS had a rather severe axonal degeneration, incomplete recovery, and high IgG, but not IgM, antiganglioside antibody titers, ranging from 1:320 to 1:10,240. Seven (28%) of the 25 GBS patients had IgG antibody titers, ranging from 1:160 to 1:10,240. None of the ganglioside-treated patients who did not develop GBS and none of the 50 disease control subjects had IgG GM(1) antibodies. Purified IgG from the patients with high GM(1) antibodies, but not from the others, recognized epitopes at the nodes of Ranvier and the distal motor nerve terminals at the end-plate. We conclude that exogenous ganglioside injections can be immunogenic, triggering IgG antiganglioside antibodies with specificity for motor nerve terminals. In some patients with axonal GBS such antibodies may be markers or mediators of axonal involvement. C1 NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. UNIV SANTA CREU & SANTA PAU,DEPT NEUROL,BARCELONA,SPAIN. UNIV SANTA CREU & SANTA PAU,DEPT IMMUNOL,BARCELONA,SPAIN. NR 40 TC 121 Z9 123 U1 2 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1995 VL 38 IS 2 BP 218 EP 224 DI 10.1002/ana.410380214 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RN985 UT WOS:A1995RN98500013 PM 7654069 ER PT J AU GU, ZX SALOMON, H CHERRINGTON, JM MULATO, AS CHEN, MS YARCHOAN, R FOLI, A SOGOCIO, KM WAINBERG, MA AF GU, ZX SALOMON, H CHERRINGTON, JM MULATO, AS CHEN, MS YARCHOAN, R FOLI, A SOGOCIO, KM WAINBERG, MA TI K65R MUTATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE ENCODES CROSS-RESISTANCE TO 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID HIGH-LEVEL RESISTANCE; NONNUCLEOSIDE INHIBITORS; ANTIVIRAL ACTIVITY; ZIDOVUDINE AZT; HIV-1; SENSITIVITY; 2',3'-DIDEOXYCYTIDINE; 2',3'-DIDEOXYINOSINE; DERIVATIVES; VARIANTS AB Cloned variants of human immunodeficiency virus type 1 that contain the K65R mutation in reverse transcriptase have previously been shown to display approximately 10- to 30-fold resistance against 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and 2',3'-dideoxy-3'-thiacytidine. On the basis of tissue culture studies with both primary T cells and established cell lines, we now report that the K65R mutation confers approximately 12- to 15-fold resistance to 9-(2-phosphonylmethoryethyl)adenine (PMEA). Likewise, a chain termination system revealed that mutated recombinant K65R reverse transcriptase displays resistance to PMEA diphosphate, the active metabolite of PMEA, in cell-free enzyme assays. Parallel studies have shown that the M184V mutation in reverse transcriptase, associated with high-level resistance against the (-) enantiomer of 2',3' dideoxy-3'-thiacytidine, does not confer resistance to PMEA in tissue culture. Viruses and enzymes that included both the K65R and M184V mutations were resistant to PMEA and PMEA diphosphate, respectively, but only to the extent conferred by the K65R mutation alone. C1 GILEAD SCI INC,FOSTER CITY,CA 94404. MCGILL UNIV,JEWISH GEN HOSP,CTR AIDS,MONTREAL,PQ H3T 1E2,CANADA. NCI,MED BRANCH,BETHESDA,MD 20892. NR 27 TC 69 Z9 69 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1995 VL 39 IS 8 BP 1888 EP 1891 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RM378 UT WOS:A1995RM37800049 PM 7486942 ER PT J AU CLANTON, DJ BUCKHEIT, RW TERPENING, SJ KISER, R MONGELLI, N BORGIA, AL SCHULTZ, R NARAYANAN, V BADER, JP RICE, WG AF CLANTON, DJ BUCKHEIT, RW TERPENING, SJ KISER, R MONGELLI, N BORGIA, AL SCHULTZ, R NARAYANAN, V BADER, JP RICE, WG TI NOVEL SULFONATED AND PHOSPHONATED ANALOGS OF DISTAMYCIN WHICH INHIBIT THE REPLICATION OF HIV SO ANTIVIRAL RESEARCH LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; ANTIVIRAL ACTIVITY; DISTAMYCIN ANALOG ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; AIDS; MECHANISM; LYMPHOCYTES; RETROVIRUS; ANTIGEN; THERAPY; ASSAY; DYES AB A series of novel distamycin-related polyanionic compounds were compared for their anti-HIV activity. Several were highly potent inhibitors of HIV virus-induced cell killing and viral replication of a wide variety of laboratory isolates, as well as a monocytotropic virus and a clinical isolate in human peripheral:blood lymphocytes. These compounds are structurally different from other sulfonic acid containing compounds reported to be potent inhibitors of the human immunodeficiency virus (HIV) in two respects: (1) they are structurally related to the non-toxic minor groove DNA binder distamycin; and (2) a number of them contain the aromatic phosphonic acid group. The compounds that were evaluated can be categorized into monomeric or dimeric ureido structural classes incorporating the bisamido-N-methylpyrrolenaphthalene-sulfonic acid group, with differences in the number and position of the sulfonic acids on the naphthalene rings. Broader structure-activity studies were made possible through the synthesis and evaluation of the compounds containing only a single N-methylpyrrole unit, those incorporating the N-methylpyrazole structure, and compounds having the isosteric phosphonic acid group substituted for the sulfonic acid group. One of the most potent of the inhibitors was 2,2'[4,4'[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide-1,1'-dimethyl]]-4,6,8 naphthalenetrisulfonic acid] hexasodium salt, NSC 651015. This compound, the phosphonic acid analog NSC 662162, and the monomeric compound NSC 651018 were studied to determine the mechanism of their inhibitory activity. Mechanistic studies revealed that inhibition was due to the disruption of virus attachment to CD4 + -susceptible cells and a further restraint on fusion of virus and cell membranes. The relative tolerance of these compounds in mice suggests that sufficient antiviral concentrations could be reached in vivo and thus may prove valuable in the treatment of AIDS patients. C1 SO RES INST,FREDERICK RES CTR,DEPT MICROBIOL RES,FREDERICK,MD. PHARMACIA FARMITALIA CARLO ERBA,DEPT RES & DEV ONCOL,MILAN,ITALY. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ANTIVIRAL DRUG MECH LAB,FREDERICK,MD 21702. RP CLANTON, DJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CM-37818] NR 33 TC 42 Z9 45 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD AUG PY 1995 VL 27 IS 4 BP 335 EP 354 DI 10.1016/0166-3542(95)00017-G PG 20 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA RQ383 UT WOS:A1995RQ38300002 PM 8540754 ER PT J AU LIPMAN, PD CAPLAN, LJ SCHOOLER, C LEE, JS AF LIPMAN, PD CAPLAN, LJ SCHOOLER, C LEE, JS TI INSIDE AND OUTSIDE THE MIND - THE EFFECTS OF AGE, ORGANIZATION, AND ACCESS TO EXTERNAL SOURCES ON RETRIEVAL OF LIFE EVENTS SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID MEMORY AIDS AB Older and middle-aged adults recorded autobiographical events on one of two forms of a Personal History Calendar, organized either by year-of-occurrence or by life event category. In Experiment 1, calendars were completed in three stages. In Stage 1, subjects completed the calendar from memory (half were told to expect Stage 2). In Stage 2, each subject reviewed Stage 1 responses with his/her spouse. In Stage 3, subjects could consult external sources. The Event Calendar yielded the most complete Stage 1 recall only for the older group. The Year Calendar generally yielded the greatest number of events, but only when members of a couple did not expect Stage 2. In Experiment 2, subjects completed the calendars in one stage, during which they had access to external sources. The Year Calendar elicited more events than the Event Calendar, but only for older subjects. The results are discussed in terms of retrieval processes in autobiographical memory, and implications for survey-based research. C1 NIMH,BETHESDA,MD 20892. US GEN ACCOUNTING OFF,WASHINGTON,DC 20548. NR 20 TC 1 Z9 1 U1 2 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD AUG PY 1995 VL 9 IS 4 BP 289 EP 306 DI 10.1002/acp.2350090403 PG 18 WC Psychology, Experimental SC Psychology GA RQ048 UT WOS:A1995RQ04800002 ER PT J AU NORQUIST, G WELLS, KB ROGERS, WH DAVIS, LM KAHN, K BROOK, R AF NORQUIST, G WELLS, KB ROGERS, WH DAVIS, LM KAHN, K BROOK, R TI QUALITY OF CARE FOR DEPRESSED ELDERLY PATIENTS HOSPITALIZED IN THE SPECIALTY PSYCHIATRIC UNITS OR GENERAL MEDICAL WARDS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PROSPECTIVE PAYMENT SYSTEM; PSYCHOTROPIC-DRUGS; MENTAL-HEALTH; PHYSICIANS; IMPLEMENTATION; RECORD AB Background: Studies to assess quality of care have become increasingly important for research and policy purposes. Objective: To evaluate the difference in quality of care between elderly depressed patients hospitalized in specialty psychiatric units and those hospitalized in general medical wards. Methods: We reviewed retrospectively the medical charts of 2746 patients with depression hospitalized in 297 general medical hospitals in five different states. Quality of care was assessed by clinical review of explicit and implicit information contained in the medical records of patients in specialty psychiatric units (n = 1295) and general medical wards (n = 1451). We also used other secondary data sources to determine postdischarge outcomes. Results: We found that (1) a higher percentage of admissions on the psychiatric units were considered appropriate, (2) overall psychological assessment was better on the psychiatric unit, (3) patients were more likely to receive psychological services on the psychiatric wards but more likely to receive traditional general medical services on medical wards, (4) there were more inpatient general medical complications on the psychiatric wards, and (5) implicit measures of clinical status at discharge were better for those on the psychiatric unit. Conclusions: Although limited by reliance on medical record abstraction and a retrospective study design, our data indicate that the quality of care for the psychological aspects of the treatment of depression may be better on psychiatric units, while the quality of general medical components of care may be better on general medical wards. C1 NIMH,ROCKVILLE,MD 20857. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA. RAND CORP,SANTA MONICA,CA 90406. NR 35 TC 26 Z9 26 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1995 VL 52 IS 8 BP 695 EP 701 PG 7 WC Psychiatry SC Psychiatry GA RN171 UT WOS:A1995RN17100016 PM 7632123 ER PT J AU BREITNER, JCS WELSH, KA GAU, BA MCDONALD, WM STEFFENS, DC SAUNDERS, AM MAGRUDER, KM HELMS, MJ PLASSMAN, BL FOLSTEIN, MF BRANDT, J ROBINETTE, CD PAGE, WF AF BREITNER, JCS WELSH, KA GAU, BA MCDONALD, WM STEFFENS, DC SAUNDERS, AM MAGRUDER, KM HELMS, MJ PLASSMAN, BL FOLSTEIN, MF BRANDT, J ROBINETTE, CD PAGE, WF TI ALZHEIMERS-DISEASE IN THE NATIONAL-ACADEMY-OF-SCIENCES NATIONAL RESEARCH COUNCIL REGISTRY OF AGING TWIN VETERANS .3. DETECTION OF CASES, LONGITUDINAL RESULTS, AND OBSERVATIONS ON TWIN CONCORDANCE SO ARCHIVES OF NEUROLOGY LA English DT Article ID VASCULAR DEMENTIA; APOLIPOPROTEIN-E; TYPE-4 ALLELE; PREVALENCE; DIAGNOSIS; CRITERIA; LOCUS; GENE; CHROMOSOME-14; POPULATION AB Objectives: To detect cases of Alzheimer's disease (AD) in a large population of twins living throughout the United States and to examine concordance for AD in twins as a function of age and genotype for apolipoprotein E (APOE). Setting: Nationwide survey. Design: Multistage screening and field evaluation beginning with two telephone interviews and culminating with laboratory tests, longitudinal neuropsychological measures, physician examination, and diagnostic consensus among experts. Participants: Membership in 1990-1991 of intact pairs in the National Academy of Sciences-National Research Council Registry of veteran twins, then aged 62 to 73 years. Main Outcome Measures: Completeness of case detection was examined in collateral studies. Zygosity and APOE genotypes were determined by restriction mapping. Concordance was calculated by the proband method. Results: Ninety subjects who screened positively for AD were studied in person, and 60 whose differential diagnoses included AD were followed up, as were their cotwins. Sensitivity of screening was estimated at greater than 99%, but 24% of subjects refused participation after initial screening. Seven of 38 diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually met criteria for probable or possible AD (prevalence estimate, 0.42%; 95% confidence interval, 0.29% to 0.56%), with good interrater reliability (intraclass r=.86). Excluding one discordant pair with unknown zygosity, concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4 genotype at APOE, but there were no affected co-twins of 15 probands with onset before age 70 years, no epsilon 4 allele, and no family history of AD. The mean (SD) period of discordance in the latter pairs was 11.3 (3.3) years. Conclusions: The multistage case-detection approach achieved reliable and valid diagnoses of AD with high apparent sensitivity but substantial attrition after initial screening. Genetic influences in AD at this age are limited, except among homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack the epsilon 4 allele are not rare, and their condition appears to have little genetic influence. They should be ideal for studies on environmental causes of AD. C1 DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710. DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. NIMH,SERV RES BRANCH,ROCKVILLE,MD 20857. JOHNS HOPKINS MED INST,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT PSYCHIAT,BOSTON,MA 02111. NATL ACAD SCI,INST MED,MED FOLLOW UP AGCY,WASHINGTON,DC 20418. RP BREITNER, JCS (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT,BOX 3925,DURHAM,NC 27710, USA. FU NIA NIH HHS [AG 05128, AG-07922, AG-08549] NR 55 TC 113 Z9 115 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 1995 VL 52 IS 8 BP 763 EP 771 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA RN516 UT WOS:A1995RN51600006 PM 7639628 ER PT J AU NASH, G HUTTER, RVP HENSON, DE AF NASH, G HUTTER, RVP HENSON, DE TI PRACTICE PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH LUNG-CANCER SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NEEDLE ASPIRATION BIOPSY; PROGNOSTIC IMPLICATIONS; DIAGNOSIS; MEDIASTINOSCOPY; SURVIVAL; STAGE C1 ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ 07039. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. RP NASH, G (reprint author), BAYSTATE MED CTR,DEPT PATHOL,759 CHESTNUT ST,SPRINGFIELD,MA 01199, USA. NR 40 TC 21 Z9 21 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1995 VL 119 IS 8 BP 695 EP 700 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA RN894 UT WOS:A1995RN89400010 PM 7646325 ER PT J AU KATSETOS, CD HERMAN, MM KRISHNA, L VENDER, JR VINORES, SA AGAMANOLIS, DP SCHIFFER, D BURGER, PC URICH, H AF KATSETOS, CD HERMAN, MM KRISHNA, L VENDER, JR VINORES, SA AGAMANOLIS, DP SCHIFFER, D BURGER, PC URICH, H TI CALBINDIN-D-28K IN SUBSETS OF MEDULLOBLASTOMAS AND IN THE HUMAN MEDULLOBLASTOMA CELL-LINE D283 MED SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CALCIUM-BINDING PROTEIN; MALIGNANT RHABDOID TUMOR; CENTRAL-NERVOUS-SYSTEM; PRIMITIVE NEUROECTODERMAL TUMORS; BETA-TUBULIN ISOTYPE; COMPARATIVE IMMUNOBLOT; MICROTUBULE PROTEINS; PALE ISLANDS; ECL CELLS; RAT AB Objective.-To evaluate the antigenic expression of calbindin-D-28k in surgically resected cerebellar medulloblastomas and the human medulloblastoma cell line D283 Med in relation to glial neoplasms, the human glioblastoma (U-251 MG) and rat glioma (C-6) cell lines, and other primary and metastatic brain tumors. Design.-Immunohistochemical staining was performed using an antiserum and a monoclonal antibody against calbindin-D-28k on (1) formalin-fixed, paraffin-embedded human, predominantly posterior fossa, brain tumor specimens (49 medulloblastomas, 59 glial and mesenchymal primary central nervous system tumors, 1 posterior fossa rhabdoid tumor, and 34 metastatic tumors); (2) formalin-, 70% alcohol-, or Bouin's-fixed tumor cell lines (D283 Med, U-251 MG, and C-6) maintained in a three-dimensional gelatin foam (Gelfoam matrix) system, with or without treatment with dibutyryl cyclic adenosine monophosphate; and (3) formalin-fixed, paraffin-embedded C-6 glioma cells transplanted intracerebrally to rats. Results.-Calbindin-D-28k immunohistochemical staining was detected in 20 of 49 cerebellar medulloblastomas and in cells of the human medulloblastoma cell line D283 Med grown in gelatin Gelfoam matrices, with or without treatment with dibutyryl cyclic adenosine monophosphate. In surgical resection specimens, calbindin-D-28k reactivity was evident in populations of poorly differentiated cells of classic (non-nodular) medulloblastomas (16/20) and in mature Purkinje neuronlike phenotypes in medulloblastomas with ganglion cells (4/6) but was absent in desmoplastic medulloblastomas, including in areas of neoplastic neuritogenesis (''pale islands'') (0/23). Calbindin-D-28k staining was also present in D283 Med explants for up to 29 days in vitro. Reactivity was more widespread in dibutyryl cyclic adenosine monophosphate-treated cultures, coinciding with neuronal morphologic alterations of cultured cells. Focal calbindin-D-28k staining was present in neural-like cells of an embryonal cerebellar tumor with divergent mesenchymal, epithelial, and neuroectodermal/neuroendocrine differentiation suggestive of a malignant rhabdoid tumor. No calbindin-D-28k staining was obtained in primary glial and mesenchymal (intra- and extra-axial) brain tumors (0/59), in explants of human glioblastoma cell line U-251 MG, or in the rat glioma line C-6 maintained in Gelfoam matrices or transplanted intracerebrally. Among 34 epithelial and mesenchymal tumors metastatic to the posterior fossa, only subpopulations of cells in two small-cell (neuroendocrine) carcinomas originating in the lung were calbindin positive. Conclusions.-Calbindin-D-28k expression in classic medulloblastomas, medulloblastomas with ganglion cells, and in the human medulloblastoma cell line D283 Med (which was derived from a metastatic classic medulloblastoma) suggests a phenotypic kinship between subsets of this tumor and neuronal progeny of the ventricular neuroepithelium, thus conferring additional support for its neuroblastic nature. C1 HAHNEMANN UNIV,DEPT NEUROSURG,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,DEPT NEUROL,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,DEPT RADIAT ONCOL & NUCL MED,PHILADELPHIA,PA 19102. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,IRP,CLIN BRAIN DISORDERS BRANCH,NEUROPATHOL SECT,WASHINGTON,DC 20032. JOHNS HOPKINS UNIV,SCH MED,WILMER OPHTHALMOL INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. CHILDRENS HOSP,MED CTR,DEPT PATHOL,AKRON,OH. UNIV TURIN,NEUROL CLIN 2,TURIN,ITALY. RP KATSETOS, CD (reprint author), HAHNEMANN UNIV,DEPT PATHOL,NEUROPATHOL LAB,MAIL STOP 435,BROAD & VINE ST,PHILADELPHIA,PA 19102, USA. NR 53 TC 24 Z9 24 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1995 VL 119 IS 8 BP 734 EP 743 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA RN894 UT WOS:A1995RN89400018 PM 7646332 ER PT J AU KIM, HC JHOO, WK KWAN, MS HONG, JS AF KIM, HC JHOO, WK KWAN, MS HONG, JS TI EFFECTS OF CHRONIC DEXTROMETHORPHAN ADMINISTRATION ON THE CELLULAR IMMUNE-RESPONSES IN MICE SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE CHRONIC DEXTROMETHORPHAN; CELLULAR IMMUNE RESPONSES ID PHENCYCLIDINE AB We examined the chronic effect of dextromethorphan (DM) on the cellular immune responses in mice. T cell stimulator, phytohemagglutinin did not show significant effect on lymphocyte proliferation. Costimulator of T and B cell, pokeweed mitogen, and B cell stimulator, lipopolysaccharide exhibited DM-induced decreased lymphocyte proliferation. Significantly suppressed natural killer (NK) cell cytotoxicity was evidenced following 6 months DM exposure. These results suggest that chronic DM administration perturb B cell functioning and NK cell cytotoxicity. In addition, prenatal DM exposure did not potentiate the immunomodulation in postnatal effect induced by chronic-DM. C1 KANGWEON NATL UNIV,COLL PHARM,CHUNCHON 200701,SOUTH KOREA. KANGWEON NATL UNIV,COLL ANIM AGR,CHUNCHON 200701,SOUTH KOREA. NIEHS,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NR 12 TC 6 Z9 6 U1 1 U2 1 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD AUG PY 1995 VL 18 IS 4 BP 267 EP 270 DI 10.1007/BF02976411 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV849 UT WOS:A1995RV84900009 ER PT J AU INSEL, TR HULIHAN, TJ AF INSEL, TR HULIHAN, TJ TI A GENDER-SPECIFIC MECHANISM FOR PAIR BONDING - OXYTOCIN AND PARTNER PREFERENCE FORMATION IN MONOGAMOUS VOLES SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID FEMALE PRAIRIE VOLES; MICROTUS-OCHROGASTER; SOCIAL RECOGNITION; SEXUAL-BEHAVIOR; ARGININE-VASOPRESSIN; RECEPTOR-BINDING; RATS; PROGESTERONE; STIMULATION; INDUCTION AB Previous studies have demonstrated that central administration of vasopressin but not oxytocin facilitates pair bonding in the monogamous male prairie vole. This study tested vasopressin and oxytocin in the formation of the female vole's preference for a particular male partner. Initial studies showed that in monogamous female prairie voles (but not in nonmonogamous congeners), mating was followed by a partner preference that endured for at least 2 weeks. Nonmating prairie vole females developed a partner preference following oxytocin infusions, but not after vasopressin or cerebrospinal fluid infusions. Females given a selective oxytocin antagonist showed normal mating behavior, yet failed to develop a partner preference. The vasopressin antagonist failed to block partner preference formation in mated females. These results suggest that oxytocin, released with mating, may be critical to formation of a partner preference in the female prairie vole; this contrasts to vasopressin, which appears to be more important for pair bonding in the male of this species. C1 NIMH,BETHESDA,MD 20892. NR 41 TC 263 Z9 270 U1 9 U2 51 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD AUG PY 1995 VL 109 IS 4 BP 782 EP 789 DI 10.1037//0735-7044.109.4.782 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA RN164 UT WOS:A1995RN16400021 PM 7576222 ER PT J AU SHOAIB, M SHIPPENBERG, TS GOLDBERG, SR SCHINDLER, CW AF SHOAIB, M SHIPPENBERG, TS GOLDBERG, SR SCHINDLER, CW TI BEHAVIORAL-STUDIES WITH THE GLYCINE PARTIAL AGONIST (+)-HA966 ON COCAINE-INDUCED LOCOMOTOR-ACTIVITY AND REINFORCEMENT SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE COCAINE; GLYCINE; LOCOMOTOR ACTIVITY; NMDA; RAT; SELF-ADMINISTRATION; SENSITIZATION ID NMDA RECEPTOR ANTAGONIST; D-ASPARTATE RECEPTOR; INDUCED SENSITIZATION; NUCLEUS-ACCUMBENS; RAT; ACTIVATION; SYSTEM; R-(+)-HA-966; PHARMACOLOGY; AMPHETAMINE AB Recent evidence suggests that excitatory amino acids may play a critical role in the mediation of the behavioral effects of cocaine. The present experiments were designed to examine the effects of the glycine-site partial agonist (+)-HA966, a compound modulating NMDA receptor function, on the development of sensitization the locomotor activating effects of cocaine and on intravenous cocaine self-administration. After chronic cocaine pretreatment (20 mg/kg i.p. daily for 3 days), Sprague-Dawley rats showed much greater increases in activity after a cocaine challenge (20 mg/kg i.p.) than did saline-pretreated controls. This sensitized response was diminished by (+)-HA966 (30, 100 and 200 mu g), when administered intraventricularly (i.c.v.) 5 min before each of the three cocaine pretreatment injections. (+)-HA966 when given alone for 3 days did not significantly diminish subsequent cocaine-induced locomotor activity. However, a small dose of (+)-HA966 (30 mu g) potentiated the acute stimulatory effects of cocaine on locomotor activity; higher doses were without effect. With limited daily access to intravenous cocaine (0.33 mg/kg/infusion), rats showed reliable patterns of self-administration under a fixed-ratio 3 (FR3) schedule of reinforcement. Pretreatment with small doses of (+)-HA966 administered 5 min prior to cocaine self-administration sessions had little effect. However, larger doses (100 and 200 mu g i.c.v.) significantly decreased responding. This effect was selective, since similar doses produced significantly less suppression of operant responding for food. The non-competitive NMDA receptor antagonist, dizocilpine (0.03-0.3 mg/kg i.p.) administered 30 min prior to sessions, significantly decreased cocaine self-administration without modifying behavior maintained by food. The present findings demonstrate that modulation of NMDA systems can significantly modify the behavioral effects of cocaine. RP SHOAIB, M (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BALTIMORE,MD 21224, USA. NR 27 TC 35 Z9 35 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 1995 VL 6 IS 5-6 BP 568 EP 576 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RW098 UT WOS:A1995RW09800015 ER PT J AU SHOAIB, M SCHINDLER, CW GOLDBERG, SR PAULY, JR AF SHOAIB, M SCHINDLER, CW GOLDBERG, SR PAULY, JR TI BEHAVIORAL AND BIOCHEMICAL ADAPTATIONS TO NICOTINE IN RATS - INFLUENCE OF DIZOCILPINE (MK-801), AN NMDA RECEPTOR ANTAGONIST SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. MED COLL GEORGIA,DEPT PHARMACOL & TOXICOL,AUGUSTA,GA 30912. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 1995 VL 6 IS 5-6 BP 632 EP 633 DI 10.1097/00008877-199508000-00077 PG 2 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RW098 UT WOS:A1995RW09800075 ER PT J AU WITKIN, JM STEELE, TD GETERDOUGLASS, B TORTELLA, FC AF WITKIN, JM STEELE, TD GETERDOUGLASS, B TORTELLA, FC TI PRECLINICAL PHARMACOLOGY OF LIGANDS ACTING AT THE STRYCHNINE-INSENSITIVE GLYCINE RECEPTOR OF THE NMDA RECEPTOR SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 1995 VL 6 IS 5-6 BP 636 EP 636 DI 10.1097/00008877-199508000-00088 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RW098 UT WOS:A1995RW09800086 ER PT J AU SURGUCHOV, AP BOERWINKLE, E SHARRETT, AR PATSCH, W AF SURGUCHOV, AP BOERWINKLE, E SHARRETT, AR PATSCH, W TI EFFECT OF APOLIPOPROTEIN-E POLYMORPHISM ON FASTING RETINYL PALMITATE LEVEL SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Note ID VITAMIN-A; METABOLISM; CLEARANCE AB The effect of apolipoprotein E (apo E) common genotypes on fasting retinyl palmitate (RP) level was studied in 344 white individuals, of which 130 had intimal thickening of the carotid artery (''cases'') and 214 were controls. In this sample the common apo E genotypes possessed a statistically significant effect on fasting RP level in cases, while in controls the effect observed was not statistically significant. It is suggested that the effect of apo E may be expressed at the level of remnant clearance particles. Additionally, in cases other traits interact with the apo E genotype to influence fasting RP level. (C) 1995 Academic Press, Inc. C1 UNIV TEXAS,CTR GENET,HOUSTON,TX 77235. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20814. RP SURGUCHOV, AP (reprint author), BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030, USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD AUG PY 1995 VL 55 IS 2 BP 156 EP 157 DI 10.1006/bmme.1995.1046 PG 2 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA RR147 UT WOS:A1995RR14700010 PM 7582873 ER PT J AU LIPPINCOTTSCHWARTZ, J COLE, NB AF LIPPINCOTTSCHWARTZ, J COLE, NB TI ROLES FOR MICROTUBULES AND KINESIN IN MEMBRANE TRAFFIC BETWEEN THE ENDOPLASMIC-RETICULUM AND THE GOLGI-COMPLEX SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 654th Meeting of the Biochemical-Society CY APR 04-07, 1995 CL LEICESTER, ENGLAND SP Biochem Soc ID BREFELDIN-A; CELLS; PROTEIN; TRANSPORT; ER; IDENTIFICATION; NOCODAZOLE; SECRETION; MOVEMENT; INVITRO RP LIPPINCOTTSCHWARTZ, J (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 18 Z9 18 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1995 VL 23 IS 3 BP 544 EP 548 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU085 UT WOS:A1995RU08500024 PM 8566412 ER PT J AU LONDOS, C BRASAEMLE, DL GRUIAGRAY, J SERVETNICK, DA SCHULTZ, CJ LEVIN, DM KIMMEL, AR AF LONDOS, C BRASAEMLE, DL GRUIAGRAY, J SERVETNICK, DA SCHULTZ, CJ LEVIN, DM KIMMEL, AR TI PERILIPIN - UNIQUE PROTEINS ASSOCIATED WITH INTRACELLULAR NEUTRAL LIPID DROPLETS IN ADIPOCYTES AND STEROIDOGENIC CELLS SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 654th Meeting of the Biochemical-Society CY APR 04-07, 1995 CL LEICESTER, ENGLAND SP Biochem Soc ID HORMONE-SENSITIVE LIPASE; PHOSPHORYLATION; EXPRESSION; SEQUENCE; INSULIN; KINASE RP LONDOS, C (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Brasaemle, Dawn/0000-0002-8553-8285 NR 16 TC 86 Z9 88 U1 0 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1995 VL 23 IS 3 BP 611 EP 615 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU085 UT WOS:A1995RU08500039 PM 8566427 ER PT J AU MOULD, AP GARRATT, AN ASKARI, JA AKIYAMA, SK HUMPHRIES, MJ AF MOULD, AP GARRATT, AN ASKARI, JA AKIYAMA, SK HUMPHRIES, MJ TI REGULATION OF INTEGRIN ALPHA-5-BETA-1 FUNCTION BY ANTI-INTEGRIN ANTIBODIES AND DIVALENT-CATIONS SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Note CT 654th Meeting of the Biochemical-Society CY APR 04-07, 1995 CL LEICESTER, ENGLAND SP Biochem Soc ID CONFORMERS; ADHESION C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP MOULD, AP (reprint author), UNIV MANCHESTER,SCH BIOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND. RI Garratt, Alistair/D-9893-2013 OI Garratt, Alistair/0000-0001-9631-3041 FU Wellcome Trust NR 5 TC 8 Z9 8 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1995 VL 23 IS 3 BP S395 EP S395 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU085 UT WOS:A1995RU08500058 PM 8566283 ER PT J AU BAI, RL TAYLOR, GF CICHACZ, ZA HERALD, CL KEPLER, JA PETTIT, GR HAMEL, E AF BAI, RL TAYLOR, GF CICHACZ, ZA HERALD, CL KEPLER, JA PETTIT, GR HAMEL, E TI THE SPONGISTATINS, POTENTLY CYTOTOXIC INHIBITORS OF TUBULIN POLYMERIZATION, BIND IN A DISTINCT REGION OF THE VINCA DOMAIN SO BIOCHEMISTRY LA English DT Article ID BOVINE BRAIN TUBULIN; ANTINEOPLASTIC AGENTS; HALICHONDRIN-B; PHOMOPSIN-A; HOMOHALICHONDRIN-B; NATURAL-PRODUCTS; EXCHANGEABLE GTP; DOLASTATIN-10; MAYTANSINE; SITE AB The highly cytotoxic, sponge-derived, antimitotic macrolide polyether spongistatin 1 has been previously shown to inhibit microtubule assembly, the binding of vinblastine and GTP to tubulin, and displacement of GDP bound in the exchangeable site of tubulin. We have now examined in detail inhibition by spongistatin 1 of both [H-3]vinblastine and [H-3]dolastatin 10 binding to tubulin, We found spongistatin 1 to be a noncompetitive inhibitor of the binding of both radiolabeled drugs to tubulin, in contrast to competitive patterns obtained with vincristine versus [H-3]viriblastine and with a chiral isomer of dolastatin 10 versus [H-3]dolastatin 10. Since dolastatin 10 is itself a noncompetitive inhibitor of vinca alkaloid binding to tubulin, this implies at least three distinct binding sites for the structurally complex and diverse natural products that interfere with each others binding to tubulin and with nucleotide exchange, Spongistatin 1, in contrast to both vinca alkaloids and peptide antimitotic agents like dolastatin 10, does not induce formation of a GTP-independent, morphologically distinctive polymer (''aggregate''), We also examined eight compounds closely related structurally to spongistatin 1 (spongistatins 2-9). The most distinctive in their properties were spongistatins 6 and 8. These two compounds, despite activity comparable to spongistatin 1 as inhibitors of tubulin polymerization and [H-3]vinblastine binding, had much reduced activity as inhibitors of nucleotide exchange and [H-3]dolastatin 10 binding. Spongistatins 1 and 6 were compared for effects on dolastatin 10-induced aggregate formation in conjunction with effects on [K-3]dolastatin 10 binding. Spongistatin 6 was about 4-fold less active than spongistatin 1 as an inhibitor of aggregation and over 20-fold less active as an inhibitor of dolastatin 10 binding. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. NR 32 TC 108 Z9 110 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 1 PY 1995 VL 34 IS 30 BP 9714 EP 9721 DI 10.1021/bi00030a009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM792 UT WOS:A1995RM79200009 PM 7626642 ER PT J AU SUN, SJ AF SUN, SJ TI A GENETIC ALGORITHM THAT SEEKS NATIVE STATES OF PEPTIDES AND PROTEINS SO BIOPHYSICAL JOURNAL LA English DT Article ID AVIAN PANCREATIC-POLYPEPTIDE; NUCLEAR-MAGNETIC-RESONANCE; X-RAY-ANALYSIS; TERTIARY STRUCTURE; STRUCTURE PREDICTION; CONFORMATIONAL-ANALYSIS; POTENTIAL FUNCTION; CRYSTAL-STRUCTURE; HELIX FORMATION; LATTICE MODEL AB We describe a computer algorithm to predict native structures of proteins and peptides from their primary sequences, their known native radii of gyration, and their known disulfide bonding patterns, starting from random conformations. Proteins are represented as simplified real-space main chains with single-bead side chains. Nonlocal interactions are taken from structural database-derived statistical potentials, as in an earlier treatment. Local interactions are taken from simulations of (phi,psi) energy surfaces for each amino acid generated using the Biosym Discover program. Conformational searching is done by a genetic algorithm-based method. Reasonable structures are obtained for melittin (a 26-mer), avian pancreatic polypeptide inhibitor (a 36-mer), crambin (a 46-mer), apamin (an 18-mer), tachyplesin (a 17-mer), C-peptide of ribonuclease A (a 13-mer), and four different designed helical peptides. A hydrogen bond interaction was tested and found to be generally unnecessary for helical peptides, but it helps fold some sheet regions in these structures. For the few longer chains we tested, the method appears not to converge. In those cases, it appears to recover native-like secondary structures, but gets incorrect tertiary folds. RP SUN, SJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 55 TC 28 Z9 29 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1995 VL 69 IS 2 BP 340 EP 355 PG 16 WC Biophysics SC Biophysics GA RX251 UT WOS:A1995RX25100005 PM 8527647 ER PT J AU SAROFF, HA AF SAROFF, HA TI ENERGETICS OF PROTEIN-DNA INTERACTIONS - AN EXACT CALCULATION FOR BINDING OF LIGANDS TO A LATTICE OF OVERLAPPING SITES SO BIOPOLYMERS LA English DT Article ID NON-COOPERATIVE BINDING; GENE 32 PROTEIN AB Exact equations are developed for analyzing the binding of ligands to a linear lattice of over lapping sites in which occupied-unoccupied as well as occupied-occupied interactions are included for the analysis of the binding isotherms. We demonstrate that positive cooperativity on the binding of ligands to multiple sites may derive from either occupied-unoccupied or occupied-occupied interactions. When the binding of proteins to linear polynucleotides and DNA has exhibited positive cooperativity protein-protein (occupied-occupied), interactions have heretofore been invoked as the sole energetic source in determining the cooperative effect. Models and equations developed previously for the analysis of these binding isotherms have included only the protein-protein interactions (usually characterized with the symbol omega). The exact equations of this paper are capable of analyzing binding data in a manner to evaluate the relative importance of both occupied-unoccupied and occupied-occupied interactions. Relations derived here are employed to analyze some existing data, and the resulting parameter values ave compared to those developed with equations employing only the protein-protein (occupied-occupied) interactions. The resulting parameter values ave qualitatively different. Values of the binding constants differ by about three orders of magnitude. When only protein-protein interactions are taken into account, the resulting free energy of interaction is negative, indicating attractive forces between bound protein molecules; when both occupied-unoccupied and occupied-occupied interactions are applied, the resulting free energies of interaction are positive, indicating destabilizing forces acting primarily on the polynucleotide lattice. (C) 1995 John Wiley & Sons, Inc. RP SAROFF, HA (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 227,BETHESDA,MD 20892, USA. NR 14 TC 8 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD AUG PY 1995 VL 36 IS 2 BP 121 EP 134 DI 10.1002/bip.360360203 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RJ401 UT WOS:A1995RJ40100002 PM 7492741 ER PT J AU ORR, A IVANOVA, VS BONNER, WM AF ORR, A IVANOVA, VS BONNER, WM TI WATERBUG DIALYSIS SO BIOTECHNIQUES LA English DT Note C1 NCI,BETHESDA,MD 20892. NR 2 TC 17 Z9 18 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 1995 VL 19 IS 2 BP 204 EP 206 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN024 UT WOS:A1995RN02400009 PM 8527137 ER PT J AU DOLAN, M ALLY, A PURZYCKI, MS GILBERT, W GILLEVET, PM AF DOLAN, M ALLY, A PURZYCKI, MS GILBERT, W GILLEVET, PM TI LARGE-SCALE GENOMIC SEQUENCING - OPTIMIZATION OF GENOMIC CHEMICAL SEQUENCING REACTIONS SO BIOTECHNIQUES LA English DT Article ID DNA AB We have developed a streamlined reproducible method for performing genomic chemical sequencing reactions on the genomic DNA of Mycoplasma capricolum, which has a genome size of about 750000 base pairs and whose composition is 75% AT The general modifications that ensure reproducibility and allow the processing of multiple samples can be widely adopted to other large-scale sequencing projects, while the specific modifications to the chemical reactions are applicable to the sequencing of other DNAs with a high AT content. C1 LIFE TECHNOL,ROCKVILLE,MD. HARVARD UNIV,CAMBRIDGE,MA 02138. NIH,CAMBRIDGE,MD. RP DOLAN, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. FU NHGRI NIH HHS [R01 HGD0124] NR 10 TC 4 Z9 4 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 1995 VL 19 IS 2 BP 264 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN024 UT WOS:A1995RN02400025 PM 8527148 ER PT J AU SCHIFFMANN, R MEDIN, JA WARD, JM STAHL, S COTTLERFOX, M KARLSSON, S AF SCHIFFMANN, R MEDIN, JA WARD, JM STAHL, S COTTLERFOX, M KARLSSON, S TI TRANSFER OF THE HUMAN GLUCOCEREBROSIDASE GENE INTO HEMATOPOIETIC STEM-CELLS OF NONABLATED RECIPIENTS - SUCCESSFUL ENGRAFTMENT AND LONG-TERM EXPRESSION OF THE TRANSGENE SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; MUCOPOLYSACCHARIDOSIS TYPE-VII; CHRONIC GRANULOMATOUS-DISEASE; GAUCHERS-DISEASE; MICE; INFECTIONS; SPECTRUM; DEFECTS; THERAPY AB In trying to develop methods of gene therapy for Gaucher disease that will avoid the morbidity and mortality associated with bone marrow (BM) ablation, we transplanted BM stem cells transduced with a retroviral vector containing the human glucocerebrosidase cDNA into normal, nonablated, syngeneic mice. Donor BM from untreated male mice or treated with 5-fluorouracil (5-FU) was transduced ex vivo using a standard 4-day transduction protocol. Recipient female mice were injected one time only or once daily for 5 consecutive days or once a week for 5 consecutive weeks using 2 x 10(7) (untreated BM) or 2 x 10(6) (5-FU-treated BM) cells per injection, Initial transduction efficiency into colony-forming unit-spleen (CFU-S) was 80% to 100%. Recipient analysis was performed at least 6 months after the last transplantation, The best engraftment of donor stem cells, up to 5% by secondary CFU-S analysis, was obtained with multiple injections of transduced BM not previously treated with 5-FU. Polymerase chain reaction (PCR) amplification for both the transgene and the Y chromosome identified the progeny of transduced stem cells in various hematopoietic and nonhematopoietic organs. The copy number of the transgene in stem cells was 0.13 to 2.8. Transgene expression was shown by reverse transcriptase PCR, in situ hybridization, and immunohistochemistry. No serious side effects of the procedure were noted. We conclude that multiple transplants of retrovirally transduced BM cells into nonablated recipients may be a safe and effective therapeutic modality for a num ber of genetic hematopoietic disorders. This is a US government work. There are no restrictions on its use. C1 NCI,OFF LAB ANIM SCI,VET TUMOR PATHOL SECT,FREDERICK,MD 21701. NIH,BETHESDA,MD 20892. RP SCHIFFMANN, R (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,MOLEC & MED GENET SECT,BLDG 10,ROOM 3D03,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 38 Z9 38 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 AUG 1 PY 1995 VL 86 IS 3 BP 1218 EP 1227 PG 10 WC Hematology SC Hematology GA RM450 UT WOS:A1995RM45000046 PM 7620175 ER PT J AU GRAFMAN, J LITVAN, I STARK, M AF GRAFMAN, J LITVAN, I STARK, M TI NEUROPSYCHOLOGICAL FEATURES OF PROGRESSIVE SUPRANUCLEAR PALSY SO BRAIN AND COGNITION LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; SUBCORTICAL DEMENTIA; COGNITIVE IMPAIRMENT; ATTENTION; CIRCUITS; BEHAVIOR; DEFICITS; PATTERN AB Progressive supranuclear palsy (PSP) is the epitome of a subcortical dementia process. Due to its relative rarity, there is only a small literature on the neuropsychological consequences of PSP. The findings to date demonstrate that PSP patients have dramatically slowed information processing and motor execution, rapid forgetting, problems in orienting attentional resources, and difficulty in planning and shifting conceptual sets. The pattern and severity of these deficits are unique to PSP and suggest that the study of PSP patients can provide a special insight into brain-behavior relations. (C) 1995 Academic Press, Inc. C1 NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. RP GRAFMAN, J (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5S209,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 44 TC 36 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD AUG PY 1995 VL 28 IS 3 BP 311 EP 320 DI 10.1006/brcg.1995.1260 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA RT796 UT WOS:A1995RT79600009 PM 8546857 ER PT J AU ALOIA, MS LONG, CJ ALLEN, JB AF ALOIA, MS LONG, CJ ALLEN, JB TI DEPRESSION AMONG THE HEAD-INJURED AND NON-HEAD-INJURED - A DISCRIMINANT-ANALYSIS SO BRAIN INJURY LA English DT Article ID MEMORY; DEFICITS; STATE AB Neuropsychologists often use traditional psychological tests to assess depression following a head injury; but the assumption that depression with a head injury resembles that in an uninjured person is suspect. The current study attempts to examine the cognitive manifestations of depression with and without a coexisting head-injury. Advanced statistical methods are used to assess whether or not the two depressions 'look alike' with respect to the neuropsychological sequelae of the disorders. A total of 1182 people were entered into one of two discriminant function analyses (DFA) for depression. Each person was a member of one of the following groups: (a) depressed, (b) non-depressed, (c) head-injured, or (d) head-injured and depressed. Two functions were performed for depression, one on the population of head-injured people and one on the population of uninjured people. Cross-validations were performed for each population and across populations in order to assess the utility of each population's function for the opposite group. This comparison allows the researcher to indirectly compare depression in the two populations. Both functions were successfully applied to either population when MMPI variables were included in the analyses. However, when only cognitive variables were included the function performed on the non-head-injured population did not correctly classify head-injured people as depressed or non-depressed. One explanation for this is that the range of cognitive scores in head-injured people is so great that it allows for a less accurate but more generalizable function. Suggestions for future research are discussed. C1 UNIV MISSISSIPPI,UNIVERSITY,MS 38677. MEMPHIS STATE UNIV,MEMPHIS,TN 38152. RP ALOIA, MS (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 21 TC 9 Z9 10 U1 0 U2 2 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD AUG-SEP PY 1995 VL 9 IS 6 BP 575 EP 583 DI 10.3109/02699059509008216 PG 9 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA RU016 UT WOS:A1995RU01600004 PM 7581353 ER PT J AU RIZZO, LV AF RIZZO, LV TI THE USE OF ORAL TOLERANCE AS A THERAPY FOR OCULAR AUTOIMMUNITY SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT XX Annual Meeting of the Brazilian-Society-of-Immunology CY SEP 10-13, 1995 CL ANGRA DOS REIS, BRAZIL SP Brazilian Soc Immunol DE TOLERANCE; AUTOIMMUNITY; UVEITIS; THERAPY; EYE; CYTOKINES ID MYELIN BASIC-PROTEIN; IMMUNE-RESPONSES; II COLLAGEN; SUPPRESSION; ANTIGEN; ENCEPHALOMYELITIS; MECHANISMS; REJECTION; UVEORETINITIS; TOLERIZATION AB Mucosal surfaces throughout the body are the main protective structures against the heavy antigen burden from the environment. The ability to distinguish between noxious agents that should be kept in check and innocuous or beneficial substances that should be ignored is one of the most interesting phenomenon in immunology. Oral tolerance is the phenomenon by which exposure to a soluble antigen through the mucosal surface results in subsequent inability to mount an immune response to the same antigen upon challenge by a different route. This type of tolerance-inducing mechanism has been recognized for many years as an effective approach to induce peripheral tolerance to soluble proteins. Recent achievements in the use of oral tolerance in the treatment of autoimmune diseases are reviewed here. Special emphasis is placed on the use of this immunotherapeutic approach to uveitis. The role of cytokines, CD4+ cells, CD8+ cells, as well as the putative mechanisms by which oral tolerance is induced, are discussed. RP RIZZO, LV (reprint author), NEI, IMMUNOREGULAT SECT,IMMUNOL LAB, 9000 ROCKVILLE PIKE,BLDG 10, ROOM 10N202, BETHESDA, MD 20892 USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 39 TC 0 Z9 0 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, 00, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD AUG PY 1995 VL 28 IS 8 BP 931 EP 936 PG 6 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA RX535 UT WOS:A1995RX53500015 PM 8555998 ER PT J AU KLEINERMAN, RA BOICE, JD STORM, HH SPAREN, P ANDERSEN, A PUKKALA, E LYNCH, CF HANKEY, BF FLANNERY, JT AF KLEINERMAN, RA BOICE, JD STORM, HH SPAREN, P ANDERSEN, A PUKKALA, E LYNCH, CF HANKEY, BF FLANNERY, JT TI 2ND PRIMARY-CANCER AFTER TREATMENT FOR CERVICAL-CANCER - AN INTERNATIONAL CANCER REGISTRIES STUDY SO CANCER LA English DT Article DE CERVICAL CANCER; RADIOTHERAPY; 2ND CANCER; LATE EFFECTS ID HUMAN PAPILLOMAVIRUS; RADIATION; RADIOTHERAPY; MORTALITY; RISK; LEUKEMIA; EPIDEMIOLOGY; CARCINOMA; LYMPHOMA; VULVA AB Background. The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects. Methods. Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors. Results. Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer. Conclusions. Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels. C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. CANC REGISTRY NORWAY,INST EPIDEMIOL CANC RES,OSLO,NORWAY. FINNISH CANC REGISTRY,INST STAT & EPIDEMIOL CANC RES,SF-00170 HELSINKI,FINLAND. UNIV IOWA,STATE HLTH REGISTRY IOWA,IOWA CITY,IA. NCI,DIV CANC PREVENT & CONTROL,CANC STAT BRANCH,BETHESDA,MD 20892. DEPT HLTH SERV,CONNECTICUT TUMOR REGISTRY,HARTFORD,CT. RP KLEINERMAN, RA (reprint author), NCI,DIV CANC ETIOL,RADIAT EPIDEMIOL BRANCH,EPN 408,6130 EXECUT BLVD MSC 7362,BETHESDA,MD 20892, USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP-85638-02, N01-CP-85626-01, N01-CP-85639-03] NR 42 TC 115 Z9 117 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 AUG 1 PY 1995 VL 76 IS 3 BP 442 EP 452 DI 10.1002/1097-0142(19950801)76:3<442::AID-CNCR2820760315>3.0.CO;2-L PG 11 WC Oncology SC Oncology GA RK630 UT WOS:A1995RK63000014 PM 8625126 ER PT J AU DAWSON, NA COOPER, MR FIGG, WD HEADLEE, DJ THIBAULT, A BERGAN, RC STEINBERG, SM SAUSVILLE, EA MYERS, CE SARTOR, O AF DAWSON, NA COOPER, MR FIGG, WD HEADLEE, DJ THIBAULT, A BERGAN, RC STEINBERG, SM SAUSVILLE, EA MYERS, CE SARTOR, O TI ANTITUMOR-ACTIVITY OF SURAMIN IN HORMONE-REFRACTORY PROSTATE-CANCER CONTROLLING FOR HYDROCORTISONE TREATMENT AND FLUTAMIDE WITHDRAWAL AS POTENTIALLY CONFOUNDING VARIABLES SO CANCER LA English DT Article DE PROSTATIC NEOPLASMS; SURAMIN; HYDROCORTISONE; FLUTAMIDE; PROSTATE SPECIFIC ANTIGEN ID GROWTH-FACTOR RECEPTOR; ADAPTIVE-CONTROL; CELLS; INHIBITION; CARCINOMA; FEEDBACK; DISEASE; ANTIGEN; DRUG AB Background. A prospective Phase II clinical trial was conducted to assess the clinical activity of a pharmacokinetically guided suramin regimen in patients who had documented progression of metastatic prostate cancer after hydrocortisone plus antecedent or simultaneous withdrawal of flutamide. Methods. Fifty-four patients whose disease had progressed after castration and flutamide administration were enrolled on this trial. The study was divided into two parts. Initially, 52 patients received hydrocortisone (30 mg/day) and for those patients receiving flutamide, at study entry (34 patients) flutamide was simultaneously discontinued. Forty-three patients whose disease progressed on hydrocortisone received suramin for 6-8 weeks. Six patients who progressed on hydrocortisone became ineligible for suramin due to clinical deterioration, four patients are still responding to hydrocortisone at more than 1 year, and one patient elected to postpone initiation of suramin. Suramin was given as intermittent infusions at fixed doses on days 1-5 and thereafter dosing was guided by adaptive control with feedback to maintain plasma suramin concentrations between 300-175 mu g/ml, Antitumor activity was assessed by prostate specific antigen (PSA) decline and soft-tissue disease response. Results. Ten patients (19%; 95% CI, 9.6%-32.5%) responded to hydrocortisone therapy with either a 50% or greater PSA decline for at least 4 weeks (9 patients) and/or a partial response of measurable soft-tissue disease (2 patients). Five of these patients (10%) demonstrated a 80% or greater PSA decline. All responders to hydrocortisone had simultaneous flutamide withdrawal, and had been receiving flutamide as part of initial combined androgen blockade. Seven of 37 evaluable patients (19%; 95% CI, 8.0%-35.2%) responded to suramin with a 50% or greater decline in PSA for 4 weeks or longer. One patient (3%) had a 80% or greater decline in PSA, There were no soft-tissue disease responses to suramin, The median time to progression was 1.9 months for hydrocortisone therapy and 2.6 months for suramin therapy. The median survival for all patients was 14.6 months. Conclusion. Suramin has antitumor activity in metastatic prostate carcinoma independent of the therapeutic effect of hydrocortisone administration or flutamide withdrawal. The role of prior flutamide withdrawal and hydrocortisone replacement should be taken into account in future studies of suramin. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. RP DAWSON, NA (reprint author), WALTER REED ARMY MED CTR,HEMATOL ONCOL SERV,WASHINGTON,DC 20307, USA. RI Figg Sr, William/M-2411-2016 NR 43 TC 56 Z9 58 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 AUG 1 PY 1995 VL 76 IS 3 BP 453 EP 462 DI 10.1002/1097-0142(19950801)76:3<453::AID-CNCR2820760316>3.0.CO;2-E PG 10 WC Oncology SC Oncology GA RK630 UT WOS:A1995RK63000015 PM 8625127 ER PT J AU WIDEMANN, BC HETHERINGTON, ML MURPHY, RF BALIS, FM ADAMSON, PC AF WIDEMANN, BC HETHERINGTON, ML MURPHY, RF BALIS, FM ADAMSON, PC TI CARBOXYPEPTIDASE-G(2) RESCUE IN A PATIENT WITH HIGH-DOSE METHOTREXATE-INDUCED NEPHROTOXICITY SO CANCER LA English DT Article DE HIGH DOSE METHOTREXATE; ACUTE RENAL FAILURE; METHOTREXATE TOXICITY; CARBOXYPEPTIDASE-G(2) ID THYMIDINE; TOXICITY; LEUCOVORIN; HEMODIALYSIS; METABOLITE; HUMANS; DRUG AB Background. High dose methotrexate (HDMTX) induced renal failure is a medical emergency, as methotrexate (MTX) is primarily eliminated by renal excretion. High doses of leucovorin (LV) do not necessarily prevent toxicity in the presence of sustained elevated plasma MTX concentrations. The bacterial enzyme carboxypeptidase-G(2) (CPDG(2)) hydrolyzes MTX into inactive metabolites and has been demonstrated to lower plasma MTX concentrations to nontoxic levels rapidly in the nonhuman primate after HDMTX infusion. Therefore, CPDG(2) was evaluated as a rescue agent in a patient with acute renal dysfunction secondary to HDMTX. Methods. A 16 year old patient with osteosarcoma experienced acute renal dysfunction after HDMTX administration, which resulted in markedly elevated and sustained plasma MTX concentrations. She received three doses of CPDG(2) on the fifth day after HDMTX. Plasma MTX concentrations were determined before and after CPDG(2) administration. Results. The plasma MTX concentrations decreased from 60 to 1.2 mu M within 15 minutes after the first dose of CPDG(2). No rebound increase in plasma MTX concentrations or adverse reactions to the enzyme were observed. The patient developed only mild mucositis. Serum creatinine at the time of CPDG(2) administration was 5 mg/dl and returned to normal within 7 weeks of enzyme administration. Conclusions. Carboxypeptidase-G(2) rapidly, markedly, and persistently lowered plasma MTX concentrations to a level that could be rescued safely with LV. Based on the experience with this patient and on preclinical studies in nonhuman primates, CPDG(2) appears to be more effective than hemodialysis or hemoperfusion, and may prove beneficial for patients at risk for life-threatening toxicity secondary to delayed excretion of MTX. C1 CHILDRENS MERCY HOSP,KANSAS CITY,MO 64108. RP WIDEMANN, BC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 47 Z9 50 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 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1995 VL 76 IS 3 BP 521 EP 526 DI 10.1002/1097-0142(19950801)76:3<521::AID-CNCR2820760325>3.0.CO;2-M PG 6 WC Oncology SC Oncology GA RK630 UT WOS:A1995RK63000024 PM 8625136 ER PT J AU SUPKO, JG HICKMAN, RL GREVER, MR MALSPEIS, L AF SUPKO, JG HICKMAN, RL GREVER, MR MALSPEIS, L TI PRECLINICAL PHARMACOLOGICAL EVALUATION OF GELDANAMYCIN AS AN ANTITUMOR AGENT SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE ANSAMYCINS; ANTINEOPLASTIC AGENTS; PHARMACOKINETICS ID TYROSINE KINASE-ACTIVITY; ANTI-TUMOR ANTIBIOTICS; HUMAN-LEUKEMIC-CELLS; ROUS-SARCOMA VIRUS; HERBIMYCIN-A; INHIBITION; PHARMACOKINETICS; DIFFERENTIATION; DERIVATIVES; METABOLISM AB The plasma pharmacokinetics of the antitumor antibiotic geldanamycin (GM; NSC 122750), a naturally occurring benzoquinoid ansamycin, was characterized in mice and a beagle dog. Concentrations of GM well above 0.1 mu g/ml, which was typically effective against neoplastic cell lines responsive to the drug in vitro, were achieved in the plasma of the mice and the dog treated by i.v. injection. However, the systemic duration of the drug was relatively short. Plasma levels decayed below 0.1 mu g/ml within 3-4 h after administration of the apparent maximum tolerated doses, which were approximately 20 mg/kg for the mice and 4 mg/kg for the dog. The drug exhibited linear pharmacokinetic behavior within the dose ranges studied. However, there were significant interspecies differences in its disposition. Whereas the mean biological half-life of GM was slightly longer in the mice (77.7 min) than in the dog (57.9 min), its mean residence time in the dog (46.6 min) was more than twofold greater than that observed in the mice (20.7 min). Nevertheless, the drug was cleared from plasma much faster by the dog (49.4 ml/min per kg) than by the mice (30.5 ml/min per kg). These apparent anomalies were principally associated with differences in the relative significance of the terminal phase upon overall drug disposition. The liver appeared to be the principal target organ of acute drug toxicity in the dog. Doses of 2.0 and 4.2 mg/kg both produced elevations in serum levels of the transaminases and other indicators of liver function characteristic of acute hepatic necrosis. Additional effects included symptoms of minor gastrointestinal toxicity and alterations in serum chemistry parameters consistent with less severe nephrotoxicity. Drug-related toxicity appeared to be reversible. In consideration of the potential for acute hepatotoxic reactions to GM, as well as to the other benzoquinoid ansamycins based upon structural analogy, additional pharmacological and therapeutic information is required to ascertain whether these compounds are viable candidates for clinical development. C1 PATHOL ASSOC INC,FREDERICK,MD 21701. RP SUPKO, JG (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PHARMACEUT CHEM LAB,FREDERICK,MD 21701, USA. NR 39 TC 364 Z9 388 U1 1 U2 15 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD AUG PY 1995 VL 36 IS 4 BP 305 EP 315 DI 10.1007/BF00689048 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA RJ661 UT WOS:A1995RJ66100007 PM 7628050 ER PT J AU NILBERT, M RYDHOLM, A MITELMAN, F MELTZER, PS MANDAHL, N AF NILBERT, M RYDHOLM, A MITELMAN, F MELTZER, PS MANDAHL, N TI CHARACTERIZATION OF THE 12Q13-15 AMPLICON IN SOFT-TISSUE TUMORS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MALIGNANT FIBROUS HISTIOCYTOMA; INSITU HYBRIDIZATION; HUMAN SARCOMAS; GENE; AMPLIFICATION; CHROMOSOME-12; MDM2; LOCALIZATION; PROTEIN; GLI AB Amplification of the genes MDM2, SAS, and CDK4, all located on the long arm of chromosome 12, has recently been demonstrated in human soft tissue tumors. To determine the extent of the amplification unit, we examined 16 soft tissue tumor samples, including pleomorphic liposarcoma, malignant fibrous histiocytoma (MFH), and atypical lipoma, by Southern blot analysis using 13 chromosome 12 probes. All tumors had previously been shown to have 3- to 20-fold amplification of MDM2. In five samples, all MFH, only MDM2 was amplified, whereas in the remaining 11 samples, two to five additional genes were amplified. The amplicon included markers both proximal and distal to MDM2, but was in all but one atypical lipoma confined to the chromosome region 12q13-15. Discontinuous amplicons were found in two of the tumors. This study indicates that MDM2, or possibly an as-yet-unidentified gene in its proximity, is the target gene of the 12q13-15 amplification in soft tissue tumors. C1 UNIV LUND HOSP,DEPT ORTHOPED,S-22185 LUND,SWEDEN. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD. RP NILBERT, M (reprint author), UNIV LUND HOSP,DEPT CLIN GENET,S-22185 LUND,SWEDEN. NR 34 TC 89 Z9 91 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD AUG PY 1995 VL 83 IS 1 BP 32 EP 36 DI 10.1016/S0165-4608(95)00016-X PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA RT846 UT WOS:A1995RT84600007 PM 7656201 ER PT J AU TAKAI, S CHAN, AML YAMADA, K MIKI, T AF TAKAI, S CHAN, AML YAMADA, K MIKI, T TI ASSIGNMENT OF THE HUMAN TIM PROTOONCOGENE TO 7Q33-]Q35 SO CANCER GENETICS AND CYTOGENETICS LA English DT Note ID INSITU HYBRIDIZATION; GENE; PSEUDOGENE; YEAST; CDC24 AB The human transforming gene TIM has been mapped to human chromosome 7 region q33-->q35 by fluorescence in situ hybridization with R-banded chromosomes. Rearrangements within this region have been reported to occur in acute myeloid leukemia cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP TAKAI, S (reprint author), INT MED CTR JAPAN,RES INST,DEPT GENET,SHINJUKU KU,1-21-1 TOYAMA CHO,TOKYO 162,JAPAN. NR 18 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD AUG PY 1995 VL 83 IS 1 BP 87 EP 89 DI 10.1016/S0165-4608(95)00017-8 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA RT846 UT WOS:A1995RT84600018 PM 7656213 ER PT J AU TOMASZEWSKI, JG DELAPENA, L GANTZ, SB BERANTO, DL WOOLERYANTILL, M DILORENZO, K MOLENDA, J FOLTS, S AF TOMASZEWSKI, JG DELAPENA, L GANTZ, SB BERANTO, DL WOOLERYANTILL, M DILORENZO, K MOLENDA, J FOLTS, S TI THE IMMUNE-SYSTEM AND CANCER SO CANCER NURSING LA English DT Article RP TOMASZEWSKI, JG (reprint author), NIH,CTR CLIN,CANC HUMAN GENOME NURSING SERV,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD AUG PY 1995 VL 18 IS 4 BP 313 EP 330 DI 10.1097/00002820-199508000-00009 PG 18 WC Oncology; Nursing SC Oncology; Nursing GA RL937 UT WOS:A1995RL93700009 PM 7664259 ER PT J AU KREITMAN, RJ PURI, RK PASTAN, I AF KREITMAN, RJ PURI, RK PASTAN, I TI INCREASED ANTITUMOR-ACTIVITY OF A CIRCULARLY PERMUTED INTERLEUKIN 4-TOXIN IN MICE INTERLEUKIN-4 RECEPTOR-BEARING HUMAN CARCINOMA SO CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; 3-DIMENSIONAL SOLUTION STRUCTURE; MAGNETIC-RESONANCE SPECTROSCOPY; RECOMBINANT HUMAN INTERLEUKIN-4; SINGLE-CHAIN IMMUNOTOXIN; FUSION TOXIN DAB486IL-2; CELL LEUKEMIA-CELLS; PSEUDOMONAS EXOTOXIN; ANTI-B4-BLOCKED RICIN; DIPHTHERIA-TOXIN AB We reported previously that circularly permuted interleukin-4 (IL4), composed of amino acids 38-129 of IL4 connected by a linker peptide GGNGG to amino acids 1-37, is preferable to native IL4 for fusing to the amino terminus of truncated Pseudomonas exotoxin (PE) to make a recombinant toxin, because the new ligand-toxin junction results in improved IL4 receptor (IL4R)-binding (R. J. Kreitman et al., Proc. Natl. Acad. Sci. USA, 91: 6889-6893, 1994). We now report that the improved binding of circularly permuted IL4-toxin is associated with improved antitumor activity in tumor-bearing mice. For in vivo testing, we made an improved circularly permuted IL4-toxin, termed IL4(38-37)-PE38KDEL. It contains an N38D mutation at the amino terminus, allowing improved expression and large-scale production in Escherichia call. It also contains the truncated toxin PE38KDEL, which is composed of amino acids 253-364 and 381-608 of PE, followed by KDEL. To evaluate antitumor activity, nude mice carrying s.c. tumors composed of IL4R-bearing human A431 epidermoid carcinoma cells were injected with recombinant toxins i.v. every other day for three doses. IL4(38-37)-PE38KDEL induced complete remissions in 80% of mice receiving 50 mu g/kg x 3 and 100% of mice receiving 100 mu g/kg x 3, while only 70% of mice receiving 200 mu g/kg x 3 of the native IL4-toxin IL4-PE38KDEL obtained complete remission. Disease-free survival after obtaining complete remissions was higher in mice treated with IL4(38-37)-PE38KDEL 50 mu g/Kg QOD x 3 than with IL4-PE38KDEL 200 mu g/Kg QOD x 3 (P < 0.03). IL4(38-37)-PE38KDEL and IL4-PE38KDEL exhibited similar toxicity and pharmacokinetics in the mice, indicating that the improved antitumor activity of the circularly permuted IL4-toxin was due to its improved binding to the IL4R on the target cells. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NR 54 TC 67 Z9 71 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 AUG 1 PY 1995 VL 55 IS 15 BP 3357 EP 3363 PG 7 WC Oncology SC Oncology GA RL493 UT WOS:A1995RL49300023 PM 7614471 ER PT J AU HWU, P YANG, JC COWHERD, R TREISMAN, J SHAFER, GE ESHHAR, Z ROSENBERG, SA AF HWU, P YANG, JC COWHERD, R TREISMAN, J SHAFER, GE ESHHAR, Z ROSENBERG, SA TI IN-VIVO ANTITUMOR-ACTIVITY OF T-CELLS REDIRECTED WITH CHIMERIC ANTIBODY T-CELL RECEPTOR GENES SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; NECROSIS-FACTOR; ZETA-CHAIN; CYTOKINE SECRETION; INTERFERON-GAMMA; TISSUE-CULTURE; HUMAN-MELANOMA; ANTIGEN; IMMUNOGLOBULIN; INTERLEUKIN-2 AB In an effort to broaden the applicability of adoptive cellular immunotherapy toward nonmelanoma cancers, we have designed chimeric antibody/T-cell receptor genes composed of the variable domains from mAbs joined to T-cell receptor-signaling chains. We have demonstrated that T cells retrovirally transduced with these genes can recognize antibody-defined antigens and that this recognition leads to T-cell activation, specific lysis, and cytokine release. In this study, we have examined the in vivo activity of murine T cells transduced with a chimeric receptor gene (MOv-gamma) derived from the mAb MOv18, which binds to a folate-binding protein overexpressed on most human ovarian adenocarcinomas. Nude mice that were given i.p. implants of human ovarian cancer (IGROV) cells were treated 3 days later with i.p. murine tumor-infiltrating lymphocytes (TIL) derived from an unrelated tumor. Mice treated with MOv-gamma-transduced TIL (MOV-TIL) had significantly increased survival compared to mice treated with saline only, nontransduced TIL, or Tn, transduced with a control anti-trinitrophenyl chimeric receptor gene (TNP-TIL). In another model, C57BL/6 mice were given i.v. injections of a syngeneic methylcholanthrene-induced sarcoma transduced with the folate-binding protein (FBP) gene. Three days later, mice were treated i.v. with various transduced murine TIL (derived from an unrelated tumor), followed by low-dose systemic interleukin 2. Eleven days after tumor injection, mice were sacrificed, and lung metastases were counted. In multiple experiments, mice receiving MOv-TIL had significantly fewer lung metastases than did mice treated with interleukin 2 alone, nontransduced TIL, or TNP-TIL. These studies indicate that T cells can be gene modified to react in vivo against tumor antigens, defined by mAbs. This approach is potentially applicable to a number of neoplastic and infectious diseases and may allow adoptive immunotherapy against types of cancer not previously amenable to cellular immunotherapy. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP HWU, P (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 190 Z9 193 U1 1 U2 9 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 AUG 1 PY 1995 VL 55 IS 15 BP 3369 EP 3373 PG 5 WC Oncology SC Oncology GA RL493 UT WOS:A1995RL49300025 PM 7614473 ER PT J AU GUAN, XY CARGILE, CB ANZICK, SL THOMPSON, FH MELTZER, PS BITTNER, ML TAETLE, R MCGILL, JR TRENT, JM AF GUAN, XY CARGILE, CB ANZICK, SL THOMPSON, FH MELTZER, PS BITTNER, ML TAETLE, R MCGILL, JR TRENT, JM TI CHROMOSOME MICRODISSECTION IDENTIFIES CRYPTIC SITES OF DNA-SEQUENCE AMPLIFICATION IN HUMAN OVARIAN-CARCINOMA SO CANCER RESEARCH LA English DT Article ID CANCER; ABERRATIONS; GENERATION; ONCOGENE; PROBES AB DNA sequence amplification contributes to the multistep process of carcinogenesis, and overexpression of amplified genes has been shown to contribute to the malignant phenotype. Cytogenetic analyses of human tumor cells, including ovarian malignancies, frequently show cytological evidence of DNA amplification in the form of double minutes and homogeneously staining regions. In this report, we have combined the techniques of chromosome microdissection and fluorescence in situ hybridization (P. S. Meltzer et al., Nat. Genet., 1: 24-28, 1992) to identify the composition and chromosomal origin of seven homogeneously staining regions from seven cases of ovarian cancer. Twelve specific chromosome band regions were identified as amplified including 11q, 12p, 16p, 19p, and 19q. These results provide important insights into the organization of amplified sequences within ovarian malignancies and add further to our recognition of regions likely to harbor genes important to the development or progression of ovarian cancer. C1 NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV ARIZONA,ARIZONA CANC CTR,TUCSON,AZ 85724. UNIV TEXAS,HLTH SCI CTR,DEPT RES,SAN ANTONIO,TX 78229. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCI NIH HHS [CA41183, CA58565-01] NR 25 TC 40 Z9 41 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 AUG 1 PY 1995 VL 55 IS 15 BP 3380 EP 3385 PG 6 WC Oncology SC Oncology GA RL493 UT WOS:A1995RL49300027 PM 7614475 ER PT J AU WATSON, MA DEVEREUX, TR MALARKEY, DE ANDERSON, MW MARONPOT, RR AF WATSON, MA DEVEREUX, TR MALARKEY, DE ANDERSON, MW MARONPOT, RR TI H-RAS ONCOGENE MUTATION SPECTRA IN B6C3F1 AND C57BL/6 MOUSE-LIVER TUMORS PROVIDE EVIDENCE FOR TCDD PROMOTION OF SPONTANEOUS AND VINYL CARBAMATE-INITIATED LIVER-CELLS SO CARCINOGENESIS LA English DT Article ID PROTOONCOGENE ACTIVATION; REGRESSION-ANALYSIS; RISK ASSESSMENT; LUNG-TUMORS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; HEPATOCARCINOGENESIS; MICE; DNA; POLYMERASE; MECHANISM AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin which has been found to be nongenotoxic in short term in vitro tests but strongly carcinogenic in two stage models of hepatocellular carcinogenesis in female rats. Many recent studies have shown that after treatment of mice with various genotoxic or non-genotoxic compounds, the H-ras oncogene mutational patterns exhibited by hepatocellular tumors appear to vary specifically with the chemical. To gain insight into the mechanism of TCDD-associated carcinogenesis, susceptible B6C3F1 mice and resistant C57BL/6 mice were treated with a single dose of vinyl carbamate (VC) or vehicle, and TCDD was administered once every 2 weeks for 1 year to half of the animals in each group. Liver tumor prevalence was assessed and found to be highest in the VC+TCDD treatment groups, reaching nearly 100% at 600 days in both sexes and both strains of mice. DNA was isolated from 20 or more frozen liver tumors (if available) from each exposure group and analyzed for H-ras mutations in codon 61 by sequencing after PCR amplification of exon 2, Fifty-one percent of tumors analyzed from B6C3F1 mice treated with TCDD alone had H-ras codon 61 mutations with a pattern similar to that detected in spontaneous tumors, Seventy-eight percent of tumors from B6C3F1 mice treated with both VC and TCDD had codon 61 mutations, and most mutations were A-->T transversions in the second base as observed similarly with VC alone, In the C57BL/6 strain comparable results were found in the respective exposure groups, These data suggest that TCDD is acting as a promoter of lesions previously initiated either spontaneously or by VC. Moreover, the intrinsic resistance of both male and female C57BL/6 mice to liver tumor formation seemed to disappear after treatment with TCDD. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NR 36 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 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1995 VL 16 IS 8 BP 1705 EP 1710 DI 10.1093/carcin/16.8.1705 PG 6 WC Oncology SC Oncology GA RP924 UT WOS:A1995RP92400006 PM 7634393 ER PT J AU WANG, QZ WORLAND, PJ CLARK, JL CARLSON, BA SAUSVILLE, EA AF WANG, QZ WORLAND, PJ CLARK, JL CARLSON, BA SAUSVILLE, EA TI APOPTOSIS IN 7-HYDROXYSTAUROSPURINE-TREATED T-LYMPHOBLASTS CORRELATES WITH ACTIVATION OF CYCLIN-DEPENDENT KINASE-1 AND KINASE-2 SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; SELECTIVE INHIBITOR; ANTICANCER DRUGS; C-MYC; UCN-01; POTENT; ARREST; PHASE AB 7-Hydroxystaurosporine (UCN-01) is a potent inhibitor of protein kinase C (PKC) isozymes alpha, beta, and gamma [Seynaeve et al., Mel. Pharmacol, 45: 1207-1214, 1994] that also has antitumor effects in vivo. To determine whether inhibition of PKC can be related to inhibition of cell growth with induction of apoptosis, we compared the effects of UCN-01 to those of the highly selective bisindolylmaleimide PKC antagonist CF 109203X in leukemic T-cell lines. Both compounds potently inhibited PKC activity when added to T-cell membrane preparations and reversed phorbol ester-induced c-fos gene expression in intact cells. However, whereas UCN-01 potently inhibited growth of Jurkat, Molt-3, Molt-4, and Hut-78 cells (IC50 = 20-65 nM, irreversible after 24 h of exposure), GF 109203X had IC(50)s for cell growth of 3.6-5.0 mu M. Less than 3 h after addition, UCN-01 but not CF 109203X-treated cells displayed loss of cells with G(2)-M DNA content, appearance of a hypodiploid DNA fraction, and evidence of internucleosomal DNA fragmentation. Six h after treatment, cells appeared to accumulate with S-phase DNA content. These effects correlated with selective UCN-01 but not CF 109203X-induced decrease in total and tyrosine phosphorylation of cyclin-dependent kinases (cdks) 1 and 2, and with increases in the histone H1 kinase activities of cdk1 and cdk2. UCN-01 was relatively less potent in inhibition of properly activated cdk1 and cdk2 when added in vitro to H1 kinase assays (IC50 = 1000 and 600 nM, respectively). We conclude that inhibition of PKC alone is not sufficient to account for the actions of UCN-01 and are led to the hypothesis that inappropriate cdk activation either correlates with or actually mediates cell growth inhibition with apoptosis in T lymphoblasts exposed to UCN-01. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NR 38 TC 151 Z9 152 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1995 VL 6 IS 8 BP 927 EP 936 PG 10 WC Cell Biology SC Cell Biology GA RN567 UT WOS:A1995RN56700003 PM 8547221 ER PT J AU RAMPALLI, AM ZELENKA, PS AF RAMPALLI, AM ZELENKA, PS TI INSULIN REGULATES EXPRESSION OF C-FOS AND C-JUN AND SUPPRESSES APOPTOSIS OF LENS EPITHELIAL-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID DNA FRAGMENTATION; MACROMOLECULAR-SYNTHESIS; ENDONUCLEASE ACTIVATION; NUCLEOTIDE-SEQUENCE; GROWTH-FACTORS; DEATH; DIFFERENTIATION; PROTEIN; GENE; THYMOCYTES AB This study investigates whether insulin (a differentiation factor for lens epithelial cells) acts as a survival factor. In the absence of insulin, 6-day embryonic chicken lens epithelial explants undergo apoptosis as shown by changes in cell morphology, DNA fragmentation, and loss of trypan blue exclusion. Insulin inhibits these changes and promotes survival of the cells. Aurintricarboxylic acid suppresses the apoptosis of lens explants. In contrast to 6-day embryonic explants, 19-day embryonic explants survive in the absence of insulin, presumably due to an endogenous survival factor. To explore the mechanism of the action of insulin as a survival factor for C-day embryonic lens explants, we compared the pattern of cell cycle markers (c-fos, c-jun, c-myc, p53, histone 1-13, thymidine kinase, and cyclin B) in both apoptotic and differentiating lens explants. In the presence of insulin, the expression of c-fos and c-jun was down-regulated after an initial induction. Expression of these genes was also induced in the absence of insulin, but mRNA levels remained elevated as the cells underwent apoptosis. In contrast, expression of c-myc, p53, histone H3, thymidine kinase, and cyclin B showed only minor differences in differentiating and apoptotic cells. Since c-fos and c-jun have been shown to play a role in apoptosis in other cell types, the ability of insulin to regulate expression of these genes may be central to its ability to act as a survival factor for lens epithelial cells. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 50 TC 28 Z9 28 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1995 VL 6 IS 8 BP 945 EP 953 PG 9 WC Cell Biology SC Cell Biology GA RN567 UT WOS:A1995RN56700005 PM 8547223 ER PT J AU HU, ZY EVARTS, RP FUJIO, K MARSDEN, ER THORGEIRSSON, SS AF HU, ZY EVARTS, RP FUJIO, K MARSDEN, ER THORGEIRSSON, SS TI EXPRESSION OF FIBROBLAST GROWTH-FACTOR RECEPTORS FLG AND BEK DURING HEPATIC ONTOGENY AND REGENERATION IN THE RAT SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FGF RECEPTOR; FACTOR-ALPHA; LIVER DEVELOPMENT; POINT MUTATION; DIFFERENTIATION; FAMILY; HEPARIN; MOUSE; GENES; PROLIFERATION AB Fibroblast growth factors (FCFs) mediate their cellular responses through specific cell surface receptors. Previous studies have indicated that acidic FGF is involved in liver regeneration and hepatic differentiation via the stem cell compartment, as well as in liver development (Marsden ef al., Lab. Invest. 67: 427-433, 1992). To further define the role of acidic FCF and its receptor systems in the liver, we examined the expression and cellular localization of FCF receptor-1 (flg)and FGF receptor-2 (bek) in the liver by Northern blot analysis and in situ hybridization techniques during liver regeneration, hepatic differentiation, and ontogenesis. In the normal adult liver, flg is absent in hepatocytes, whereas a low level of bek can be detected. The transcripts for bek increased, while flg exhibited little change during liver regeneration after partial hepatectomy. Both flg and bek were expressed at high levels in the developing liver. flg was expressed at a high level in embryonic liver and further increased after birth, whereas a significant increase of bek occurred at the postnatal stage of liver development. In the 2-acetylaminofluorene/partial hepatectomy model, both flg and bek are expressed at high levels during the period of active proliferation and differentiation of oval cells. In situ hybridization showed that flg was mainly localized in oval cells, whereas bek was highly expressed in both oval and Ito cells. The data suggest that bek is involved in the proliferation of mature hepatocyte proliferation during liver regeneration, while flg is characteristic of primitive hepatic cells. Furthermore, the data indicate that both flg and bek are involved in hepatic differentiation from the liver stem cell compartment as well as in liver development. RP HU, ZY (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,37 CONVENT DR,MSC-4255,BETHESDA,MD 20892, USA. NR 38 TC 32 Z9 32 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1995 VL 6 IS 8 BP 1019 EP 1025 PG 7 WC Cell Biology SC Cell Biology GA RN567 UT WOS:A1995RN56700012 PM 8547216 ER PT J AU MONI, RW ROMERO, FS DALY, JW AF MONI, RW ROMERO, FS DALY, JW TI THE AMPHIPHILIC PEPTIDE ADENOREGULIN ENHANCES AGONIST BINDING TO A(1)-ADENOSINE RECEPTORS AND [S-35] GTP-GAMMA-S TO BRAIN MEMBRANES SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE PEPTIDES; ADENOSINE RECEPTORS; ADRENERGIC RECEPTORS; SEROTONIN RECEPTORS; GUANYL NUCLEOTIDE EXCHANGE ID A1 ADENOSINE RECEPTORS; GUANINE-NUCLEOTIDE; MOLECULAR-CLONING; BOVINE BRAIN; ADENOSINE-A1-RECEPTOR BINDING; PROTEIN-ACTIVATION; CYCLIC-AMP; 2-AMINO-3-BENZOYLTHIOPHENES; STIMULATION; INHIBITION AB 1. Adenoregulin is an amphilic peptide isolated from skin mucus of the tree frog, Phyllomedusa bicolor. Synthetic adenoregulin enhanced the binding of agonists to several G-protein-coupled receptors in rat brain membranes. 2. The maximal enhancement of agonist binding, and in parentheses, the concentration of adenoregulin affording maximal enhancement were as follows: 60% (20 mu M) for A(1)-adenosine receptors, 30% (100 mu M) for A(2a)-adenosine receptors, 20% (2 mu M) for alpha(2)-adrenergic receptors, and 30% (10 mu M) for 5HT(1A) receptors. High affinity agonist binding for A(1-), alpha(2-), and 5HT(1A)-receptors was virtually abolished by GTP gamma S in the presence of adenoregulin, but was only partially abolished in its absence. Magnesium ions increased the binding of agonists to receptors and reduced the enhancement elicited by adenoregulin. 3. The effect of adenoregulin on binding of N-6-cyclohexyladenosine ([H-3]CHA) to A(1)-receptors was relatively slow and was irreversible. Adenoregulin increased the B-max value for [H-3]CHA binding sites, and the proportion of high affinity states, and slowed the rate of [H-3]CHA dissociation. Binding of the A(1)-selective antagonist, [H-3]DPCPX, was maximally enhanced by only 13% at 2 mu M adenoregulin. Basal and A(1)-adenosine receptor-stimulated binding of [S-35]GTP gamma S were maximally enhanced 45% and 23%, respectively, by 50 mu M adenoregulin. In CHAPS-solubilized membranes from rat cortex, the binding of both [H-3]CHA and [H-3]DPCPX were enhanced by adenoregulin. Binding of [H-3]CHA to membranes from DDT1 MF-2 cells was maximally enhanced 17% at 20 mu M adenoregulin. In intact DDT1 MF-2 cells, 20 mu M adenoregulin did not potentiate the inhibition of cyclic AMP accumulation mediated via the adenosine A(1) receptor. 4. It is proposed that adenoregulin enhances agonist binding through a mechanism involving enhancement of guanyl nucleotide exchange at G-proteins, resulting in a conversion of receptors into a high affinity state complexed with guanyl nucleotide-free G-protein. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 29 TC 7 Z9 8 U1 0 U2 6 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD AUG PY 1995 VL 15 IS 4 BP 465 EP 493 DI 10.1007/BF02071881 PG 29 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TA503 UT WOS:A1995TA50300007 PM 8565049 ER PT J AU HAMAWY, MM MERGENHAGEN, SE SIRAGANIAN, RP AF HAMAWY, MM MERGENHAGEN, SE SIRAGANIAN, RP TI PROTEIN-TYROSINE PHOSPHORYLATION AS A MECHANISM OF SIGNALING IN MAST-CELLS AND BASOPHILS SO CELLULAR SIGNALLING LA English DT Review DE MAST CELLS; BASOPHILS; FC-EPSILON-RI; INTEGRIN; C-KIT; TYROSINE PHOSPHORYLATION ID CYTOPLASMIC SIGNALING PROTEINS; X-LINKED AGAMMAGLOBULINEMIA; RECEPTOR-MEDIATED SIGNAL; HIGH-AFFINITY RECEPTOR; LEUKEMIA-CELLS; C-KIT; PHOSPHOLIPASE C-GAMMA-1; T-CELL; PROTOONCOGENE PRODUCT; ANTIGEN RECEPTOR AB Tyrosine phosphorylation of proteins is a mechanism of signalling for different receptors and is important for cell growth and differentiation. Mast cells and basophils are secretory cells that play a role in inflammatory and immediate allergic reactions. The activation/aggregation of different surface receptors on these cells induces tyrosine phosphorylation of proteins. Because these signals are essential for the function of basophils and mast cells, characterizing these pathways could provide methods to specifically regulate the function of these cells. Here we discuss the signals generated by three receptors: the high affinity IgE receptor (Fc epsilon RI), the growth factor receptor, Kit, and integrins. RP HAMAWY, MM (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 90 TC 59 Z9 59 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD AUG PY 1995 VL 7 IS 6 BP 535 EP 544 DI 10.1016/0898-6568(95)00024-J PG 10 WC Cell Biology SC Cell Biology GA RU173 UT WOS:A1995RU17300001 PM 8588970 ER PT J AU GAWLEY, RE REIN, KS JEGLITSCH, G ADAMS, DJ THEODORAKIS, EA TIEBES, J NICOLAOU, KC BADEN, DG AF GAWLEY, RE REIN, KS JEGLITSCH, G ADAMS, DJ THEODORAKIS, EA TIEBES, J NICOLAOU, KC BADEN, DG TI THE RELATIONSHIP OF BREVETOXIN LENGTH AND A-RING FUNCTIONALITY TO BINDING AND ACTIVITY IN NEURONAL SODIUM-CHANNELS SO CHEMISTRY & BIOLOGY LA English DT Article DE BREVETOXIN; PATCH-CLAMP; SINGLE SODIUM CHANNEL CURRENTS; SUBCONDUCTANCE STATES; SYNAPTOSOME BINDING ID RAT-BRAIN SYNAPTOSOMES; RECEPTOR AB Background: Brevetoxins are polyether ladder toxins that are ichthyotoxic at nanomolar concentrations. They bind to voltage-gated sodium channels, causing four distinct electrophysiological effects: (i) a shift of activation potential; (ii) occurrence of subconductance states; (iii) induction of longer mean open times of the channel; and (iv) inhibition of channel inactivation. We set out to determine whether these functions all require the same structural elements within the brevetoxin molecules. Results: Several synthetically prepared structural analogs of brevetoxin B were examined in synaptosome receptor binding assays and by functional electrophysiological measurements. A truncated analog is not ichthyotoxic at micromolar concentrations, shows decreased receptor-binding affinity, and causes only a shift of activation potential without affecting mean open times or channel inactivation. An analog with the A-ring carbonyl removed binds to the receptor with nanomolar affinity, produces a shift of activation potential and inhibits inactivation, but does not induce longer mean open times. An analog in which the A-ring diol is reduced shows low binding affinity, yet populates five subconductance states. Conclusions: Our data are consistent with the hypothesis that binding to sodium channels requires an elongated cigar-shaped molecule, similar to 30 Angstrom long. The four electrophysiological effects of the brevetoxins are not produced by a single structural feature, however, since they can be decoupled by using modified ligands, which are shown here to be partial sodium channel agonists. We propose a detailed model for the binding of brevetoxins to the channel which explains the differences in the effects of the brevetoxin analogs. These studies also offer the potential for developing brevetoxin antagonists. C1 NIEHS, MARINE & FRESHWATER BIOMED SCI CTR, MIAMI, FL 33149 USA. UNIV MIAMI, SCH MED, DEPT MOLEC & CELLULAR PHARMACOL, MIAMI, FL 33101 USA. Scripps Res Inst, DEPT CHEM, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA. RP GAWLEY, RE (reprint author), UNIV MIAMI, DEPT CHEM, POB 249118, CORAL GABLES, FL 33124 USA. RI Theodorakis, Emmanuel/B-5255-2013; OI Adams, David/0000-0002-7030-2288 FU NIEHS NIH HHS [P30 ES 05705, R01 ES 05853]; NIGMS NIH HHS [R01 GM 31398] NR 20 TC 84 Z9 86 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD AUG PY 1995 VL 2 IS 8 BP 533 EP 541 DI 10.1016/1074-5521(95)90187-6 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR275 UT WOS:A1995RR27500006 PM 9383457 ER PT J AU TURNER, EH LEIBENLUFT, E ALBERT, PS WEHR, TA ROSENTHAL, NE AF TURNER, EH LEIBENLUFT, E ALBERT, PS WEHR, TA ROSENTHAL, NE TI EFFECT OF SEASON AND LIGHT TREATMENT UPON HOT FLASHES IN A PERIMENOPAUSAL SAD PATIENT SO CHRONOBIOLOGY INTERNATIONAL LA English DT Note DE MENOPAUSE; HOT FLASH FLUSH; SEASONS; SEASONAL AFFECTIVE DISORDER; PHOTOTHERAPY; CIRCADIAN RHYTHM; MELATONIN ID MELATONIN SECRETION; AFFECTIVE-DISORDER; MENSTRUAL CYCLES; REPRODUCTION; BEHAVIOR; HUMANS AB A perimenopausal woman with seasonal affective disorder (SAD, winter depression) presented with a 2-year history of hot flashes occurring only in the winter-time. Prospectively documented hot flashes appeared to follow a seasonal rhythm and a bimodal circadian rhythm. The hot flashes decreased with morning, but not evening, light therapy. These observations are discussed in the context of the literature regarding light's possible role in animal and human reproductive functioning. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,DIV INTRAMURAL RES,BETHESDA,MD 20892. RP TURNER, EH (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 26 TC 4 Z9 4 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PD AUG PY 1995 VL 12 IS 4 BP 290 EP 297 DI 10.3109/07420529509057277 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA RZ401 UT WOS:A1995RZ40100007 ER PT J AU LENFANT, C AF LENFANT, C TI ENHANCING MINORITY PARTICIPATION IN RESEARCH - THE NHLBI EXPERIENCE SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1995 VL 92 IS 3 BP 279 EP 280 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RL562 UT WOS:A1995RL56200003 PM 7634436 ER PT J AU QUYYUMI, AA DAKAK, N ANDREWS, NP GILLIGAN, DM PANZA, JA CANNON, RO AF QUYYUMI, AA DAKAK, N ANDREWS, NP GILLIGAN, DM PANZA, JA CANNON, RO TI CONTRIBUTION OF NITRIC-OXIDE TO METABOLIC CORONARY VASODILATION IN THE HUMAN HEART SO CIRCULATION LA English DT Article DE ENDOTHELIUM-DERIVED FACTORS; VASODILATION ID ENDOTHELIUM-DEPENDENT VASODILATION; RELAXING FACTOR; SMOOTH-MUSCLE; BLOOD-FLOW; VASOMOTOR RESPONSE; L-ARGININE; MEDIATED DILATION; ANGINA-PECTORIS; ARTERY DISEASE; CONSCIOUS DOGS AB Background The vascular endothelium contributes to smooth muscle relaxation by tonic release of nitric oxide. To investigate the contribution of nitric oxide to human coronary epicardial and microvascular dilation during conditions of increasing myocardial oxygen requirements, we studied the effect of inhibiting nitric oxide synthesis with N-G-monomethyl-L-arginine (L-NMMA) on the coronary vasodilation Juring cardiac pacing in patients with angiographically normal coronary arteries with and without multiple risk factors for coronary atherosclerosis. Methods and Results In 26 patients with angiographically normal or near-normal epicardial coronary arteries, metabolic vasodilation was assessed as a change in coronary vascular resistance and diameter during cardiac pacing (mean heart rate, 141 beats per minute). Endothelium-dependent vasodilation was estimated with intracoronary acetylcholine and endothelium-independent dilation with intracoronary sodium nitro-prusside and adenosine. These measurements were repeated after 64 mu mol/min intracoronary L-NMMA. At rest, L-NMMA produced a 16+/-25% (mean+/-SD) increase in coronary vascular resistance (P<.05) and an 11% reduction in distal epicardial coronary artery diameter (P<.01), indicating tonic basal release of nitric oxide from human coronary epicardial vessels and microvessels. Significant inhibition of pacing-induced metabolic coronary vascular dilation occurred with L-NMMA, coronary vascular resistance was 38+/-56% higher (P<.03), and epicardial coronary dilation during control pacing (9+/-13%) was converted to constriction after L-NMMA and pacing (-6+/-9%, P<.04). L-NMMA specifically inhibited endothelium-dependent vasodilation with acetylcholine (coronary vascular resistance was 72% higher [P<.01]) but did not alter endothelium-independent dilation with sodium nitroprusside and adenosine. Nine patients had no major risk factors for atherosclerosis, defined as serum cholesterol >240 mg/dL, hypertension, or diabetes. The remaining 17 patients with one or more of these risk factors had depressed microvascular vasodilation during cardiac pacing (coronary vascular resistance decreased by 13% versus 36% in those without risk factors, P<.05). The inhibitory effect of L-NMMA on pacing-induced coronary epicardial and microvascular vasodilation was observed only in patients without risk factors, whereas those with risk factors had an insignificant change, indicating that nitric oxide contributes significantly to pacing-induced coronary vasodilation in patients free of risk factors and without endothelial dysfunction. Patients with risk factors also had reduced vasodilation with acetylcholine (40+/-28% versus 68+/-8% decrease in coronary vascular resistance, P<.01), but the responses to sodium nitroprusside were similar in both groups. Conclusions During metabolic stimulation of the human heart, nitric oxide release contributes significantly to microvascular vasodilation and is almost entirely responsible for the epicardial vasodilation. This contribution of nitric oxide is reduced in patients exposed to risk factors for coronary atherosclerosis and leads to a net reduction in vasodilation during stress. An important implication of these findings is that reduced nitric oxide bioavailability during stress in patients with atherosclerosis or risk factors for atherosclerosis may contribute to myocardial ischemia by limiting epicardial and microvascular coronary vasodilation. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV CARDIOL,RICHMOND,VA 23298. RP QUYYUMI, AA (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,10 CTR DR,MSC 1650,BETHESDA,MD 20892, USA. NR 56 TC 223 Z9 225 U1 1 U2 6 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1995 VL 92 IS 3 BP 320 EP 326 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RL562 UT WOS:A1995RL56200011 PM 7634444 ER PT J AU GARDIN, JM WAGENKNECHT, LE ANTONCULVER, H FLACK, J GIDDING, S KUROSAKI, T WONG, ND MANOLIO, TA AF GARDIN, JM WAGENKNECHT, LE ANTONCULVER, H FLACK, J GIDDING, S KUROSAKI, T WONG, ND MANOLIO, TA TI RELATIONSHIP OF CARDIOVASCULAR RISK-FACTORS TO ECHOCARDIOGRAPHIC LEFT-VENTRICULAR MASS IN HEALTHY-YOUNG BLACK-AND-WHITE ADULT MEN AND WOMEN - THE CARDIA STUDY SO CIRCULATION LA English DT Article DE RISK FACTORS; ECHOCARDIOGRAPHY; BLOOD PRESSURE ID BLOOD-PRESSURE; HEART-DISEASE; BODY SIZE; HYPERTENSION; HYPERTROPHY; CHILDREN; IMPACT; POPULATION; GEOMETRY; AGE AB Background The objective of this study was to describe the distribution of echo left ventricular (LV) mass and its association with demographic and cardiovascular risk factors in a large race- and sex-balanced cohort of young adults. Recent epidemiological data have suggested that M-mode echocardiographically determined LV hypertrophy is an independent predictor of mortality and morbidity from coronary heart disease (CHD) in older adults. Echocardiographic LV mass has been associated in middle-aged and older adults with multiple factors including age, arterial blood pressure, body mass, and sex. However, there are few data describing the distribution of echo LV mass among black and white young adult men and women and relating LV mass to cardiovascular disease risk factors within race-sex subgroups. Methods and Results CARDIA (Coronary Artery Risk Development in Young Adults) is a multicenter study of young adults, including approximately equal proportions of black and white men and women aged 23 to 35 years at the time of echo examination (1990 through 1991). Two-dimensionally guided M-mode echocardiograms were attempted in 4243 participants with recordings deemed acceptable for calculation of LV mass, that is, of at least fair quality score, obtained in 3840 (90.5% of the 1990-1991 cohort). M-mode LV mass was calculated from the formula of Devereux and Reichek, adapted for use with measurements made according to the American Society of Echocardiography Standards. LV mass was greater in men than in women and greater in blacks than in whites (P<.001) (mean+/-SD): black men, 176+/-42 g; white men, 169+/-40 g; black women, 135+/-38 g; and white women, 125+/-33 g. In all race-sex groups, LV mass was positively correlated (P<.0001) in bivariate analyses with body weight, subscapular skinfold thickness, height, and systolic blood pressure. In multivariate analyses, LV mass remained independently and positively related to body weight and systolic blood pressure and, when body weight was not considered, with subscapular skinfold thickness and height. In addition, the multivariate models allowed us to infer a direct relation between LV mass and both fatness and lean body mass. Weaker positive associations were noted of LV mass with pulse pressure in white participants and with physical activity in men. After adjustment for subscapular skinfold thickness, height, systolic and diastolic blood pressures, alcohol consumption, pulmonary function, smoking history, physical activity, total serum cholesterol, and family history of hypertension, LV mass remained higher in men than in women (P<.0001), in black men (167+/-43 g) than in white men (156+/-50 g, P<.0001), and in black women (142+/-49 g) than in white women (137+/-43 g, P<.002). Conclusions In the healthy young adults of the CARDIA cohort, LV mass was highly correlated with body weight, subscapular skinfold thickness, height, and systolic blood pressure across race and sex subgroups. Furthermore, after adjustment for anthropometric, blood pressure, and other covariates, LV mass remained higher in men than in women and in blacks than in whites. Longitudinal studies are necessary to delineate the possible roles of these factors in the genesis of LV hypertrophy. C1 UNIV CALIF IRVINE,DEPT MED,DIV EPIDEMIOL,ORANGE,CA 92613. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NORTHWESTERN UNIV,SCH MED,CHICAGO CLIN CTR,CHICAGO,IL. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP GARDIN, JM (reprint author), UNIV CALIF IRVINE,MED CTR,DEPT MED,DIV CARDIOL,POB 14091,ORANGE,CA 92613, USA. FU NHLBI NIH HHS [H01-HC 48047, H01-HC 48048, H01-HC 48049] NR 42 TC 191 Z9 196 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1995 VL 92 IS 3 BP 380 EP 387 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RL562 UT WOS:A1995RL56200019 PM 7634452 ER PT J AU CHEN, W GABEL, S STEENBERGEN, C MURPHY, E AF CHEN, W GABEL, S STEENBERGEN, C MURPHY, E TI A REDOX-BASED MECHANISM FOR CARDIOPROTECTION INDUCED BY ISCHEMIC PRECONDITIONING IN PERFUSED RAT-HEART SO CIRCULATION RESEARCH LA English DT Article DE PRECONDITIONING; THIOL REDOX; GLUTATHIONE; ISCHEMIA REPERFUSION ID FACTOR-KAPPA-B; N-ACETYLCYSTEINE; PROTEIN PHOSPHATASE; REPERFUSION INJURY; GLUTATHIONE; METABOLISM; PROTECTION; RECOVERY; INVITRO; DAMAGE AB Recent studies have suggested that mild redox alterations can regulate cell function. Therefore, we tested the hypothesis that alteration in the thiol redox state might be responsible for the cardioprotective effects conferred by ischemic preconditioning in the perfused rat heart. We find that preconditioning with four 5-minute periods of ischemia, each separated by 5 minutes of reflow, is associated with a significant loss of glutathione (3.98+/-0.32 mu mol/g dry wt, n=8) compared with no preconditioning (6.38+/-0.24 mu mol/g dry wt, n=14). We further find that the addition of N-acetylcysteine (NAG, a glutathione precursor and antioxidant) during the preconditioning protocol not only blocks the loss of glutathione (5.60+/-0.31 mu mol/g dry wt, n=9) but also blocks the protective effects of preconditioning. It is observed that after 20 minutes of ischemia followed by 20 minutes of reflow, untreated hearts recover 38+/-7% (n=5) of their initial preischemic contractile function, whereas preconditioned hearts recover 91+/-11% (n=7). Hearts preconditioned in the presence of NAC recover 24+/-3% (n=7) of their preischemic function. Similarly, the addition of NAC reverses the protective effect of preconditioning on creatine kinase release. On reflow after 60 minutes of ischemia, creatine kinase release from control hearts was 271+/-20 IU . 20 min(-1). g dry wt(-1) (n=5), whereas preconditioned hearts release only 170+/-26 IU . 20 min(-1). g dry wt(-1) (n=6), and hearts preconditioned in the presence of NAC release 361+/-30 IU . 20 min(-1). g dry wt(-1) (n=5). We also find that hearts preconditioned in the presence of NAC have less attenuation of the decline in pH(i) than hearts preconditioned in the absence of drug. Thus, a redox-sensitive mechanism may be involved in the protection afforded by ischemic preconditioning. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. RP CHEN, W (reprint author), NIEHS,MOLEC BIOPHYS LAB,MD 4A-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NHLBI NIH HHS [R01 HL039752, R01-HL-39752] NR 31 TC 120 Z9 123 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1995 VL 77 IS 2 BP 424 EP 429 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA RK989 UT WOS:A1995RK98900025 PM 7614726 ER PT J AU CHEUNG, SC TAKEDA, S NOTKINS, AL AF CHEUNG, SC TAKEDA, S NOTKINS, AL TI BOTH V-H AND V-L CHAINS OF POLYREACTIVE IGM ANTIBODY ARE REQUIRED FOR POLYREACTIVITY - EXPRESSION OF FAB IN ESCHERICHIA-COLI SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE POLYREACTIVE ANTIBODIES; ANTIBODY GENES; FAB FRAGMENT; ESCHERICHIA COLI; EXPRESSION; SYSTEM; ANTIGEN-BINDING ID B-CELLS; 3-DIMENSIONAL STRUCTURE; CONSTANT REGION; RABIES VIRUS; GENES; AFFINITY; AUTOANTIBODIES; ANTIGENS; SEQUENCE; SELF AB Monoclonal polyreactive antibodies can bind to many structurally dissimilar self and non-self antigens. Neither the precise antigen-binding site on the polyreactive antibody molecule nor the molecular basis of polyreactivity has been elucidated. The present study was initiated to see whether antibody genes encoding the Fab fragment of a human monoclonal polyreactive IgM antibody (MoAb 67) could be efficiently expressed in Escherichia coli, and whether the bacterially expressed Fab fragments possessed biological activity. cDNA encoding the variable domains of the heavy and light chains of MoAb 67 were cloned, amplified by polymerase chain reaction (PCR) and expressed in E. coli. Neither the recombinant heavy nor light chain showed antigen-binding activity. In contrast, the recombinant Fab 67 fragment showed the same antigen-binding reactivity profile as the native IgM antibody. It is concluded that the antigen-binding activity of polyreactive antibodies resides in the Fab fragment, and that both the heavy and light chains are required for activity. RP CHEUNG, SC (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 114,30 CONVENT DR MSC 4322,BETHESDA,MD 20892, USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 1995 VL 101 IS 2 BP 383 EP 386 PG 4 WC Immunology SC Immunology GA RP219 UT WOS:A1995RP21900030 PM 7648724 ER PT J AU HARRIS, MI AF HARRIS, MI TI EPIDEMIOLOGIC STUDIES ON THE PATHOGENESIS OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM) SO CLINICAL AND INVESTIGATIVE MEDICINE-MEDECINE CLINIQUE ET EXPERIMENTALE LA English DT Article; Proceedings Paper CT Symposium on Diabetes Update - New Developments in Pathophysiology and Treatment of NIDDM CY OCT 15-16, 1994 CL VANCOUVER, CANADA SP Bayer Inc DE DIABETES MELLITUS; EPIDEMIOLOGY; POPULATION-BASED STUDIES; ETIOLOGY; PATHOGENESIS ID IMPAIRED GLUCOSE-TOLERANCE; PIMA-INDIANS; MEXICAN-AMERICANS; HIGH PREVALENCE; HIGH-RISK; HIGH-FAT; POPULATION; HYPERINSULINEMIA; DIAGNOSIS; ADULTS AB The diagnostic criteria of the US National Diabetes Data Group and the World Health Organization have stimulated a major increase throughout the world in epidemiologic studies on the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). They have established that much of NIDDM is undiagnosed, that onset of NIDDM occurs at least 7 y before its diagnosis, and that significant morbidity and premature mortality occur in subjects with undiagnosed diabetes. New studies have shown that rural or traditional-living populations are experiencing a major increase in the burden of NIDDM as they move to urban or nontraditional situations, often with 5- to 10-fold increases in NIDDM prevalence. Epidemiologic studies have documented that major risk factors for NIDDM include increasing age, greater obesity, longer duration of obesity, unfavourable body fat distribution, physical inactivity, and hyperinsulinemia. All these factors interact with unknown genetic factors to produce NIDDM. Studies have shown that genes for diabetes, as yet undetermined, are a necessary cause of NIDDM. Hyperinsulinemia exists in childhood in populations at high risk for NIDDM. Stimulated by obesity, upper body obesity, and physical inactivity, insulin resistance develops, accompanied by hypersecretion of insulin and development of impaired glucose tolerance. The pressure of the NIDDM risk factors continues this process of insulin resistance/hyperinsulinemia/hyperglycemia, until glucose toxicity to the beta cell results in inability to secrete sufficient insulin, resulting in decompensated fasting hyperglycemia. RP HARRIS, MI (reprint author), NIDDKD,NATL DIABET DATA GRP,NATCHER BLDG,ROOM 5AN24,45 CTR DR MSC6600,BETHESDA,MD 20892, USA. NR 38 TC 45 Z9 46 U1 1 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med.-Med. Clin. Exp. PD AUG PY 1995 VL 18 IS 4 BP 231 EP 239 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RQ224 UT WOS:A1995RQ22400002 PM 8549007 ER PT J AU Figg, WD Cole, KA Reed, E Steinberg, SM Piscitelli, SC Davis, PA Soltis, MJ Jacob, J Boudoulas, S Goldspiel, B Sarosy, G Liotta, LA Kohn, EC AF Figg, WD Cole, KA Reed, E Steinberg, SM Piscitelli, SC Davis, PA Soltis, MJ Jacob, J Boudoulas, S Goldspiel, B Sarosy, G Liotta, LA Kohn, EC TI Pharmacokinetics of orally administered carboxyamido-triazole, an inhibitor of calcium-mediated signal transduction SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR; L651582; TARGETS; ENTRY; AGENT AB Carboxyamido-triazole (CAI), inhibits proliferation, invasion, and metastatic potential of a number of cancer cell lines at concentrations greater than 0.4 mu g/ml. The objective of this study was to characterize the pharmacokinetic profile from the first Phase I clinical trial of CAI for the single test dose and multiple daily dosing schedule, Two different p.o. formulations (liquid and gelcap) of CAI were administered, Thirty-nine patients with cancer were enrolled, The dose escalation schema was 100, 125, and 150 mg/m(2)/day and 200 and 330 mg/m(2) every other day of the liquid formulation, plus 100 and 125 mg/m(2)/day and 200 mg/m(2) every other day of the gelcap, The CAI pharmacokinetics are best described by a two compartment open linear model, The gelcap was more rapidly absorbed than the liquid [time to maximum plasma concentration (T-max) = 2.06 +/- 1.02 versus 5.31 +/- 3.59 h, P-2 = 0.0012] which resulted in higher peak plasma concentrations, There was no evidence of saturable elimination as the dose was increased, The mean steady-state peak concentration was 5.1 +/- 1.0 mu g/ml for the 150 mg/m(2)/day multiple daily dosing regimen, The terminal half-life of CAI was relatively prolonged, 111 h, and the total body p.o. clearance was low (1.87 liters/h), The peak concentration for all dose levels explored was greater than the targeted concentration suggested by in vitro data for activity, Thus, these data suggest that an effective cytostatic exposure of CAI may be obtained with daily or every other day dosing without severe toxicity. C1 NCI,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BETHESDA,MD 20892. NCI,PATHOL LAB,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. RI Cole, Kristina/M-3922-2015; Figg Sr, William/M-2411-2016 NR 27 TC 17 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1995 VL 1 IS 8 BP 797 EP 803 PG 7 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300003 PM 9816048 ER PT J AU Lorimer, IAJ Wikstrand, CJ Batra, SK Bigner, DD Pastan, I AF Lorimer, IAJ Wikstrand, CJ Batra, SK Bigner, DD Pastan, I TI Immunotoxins that target an oncogenic mutant epidermal growth factor receptor expressed in human tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; LIGAND-BINDING DOMAIN; RECOMBINANT FORM; KINASE-ACTIVITY; ANTIBODIES; TOXIN; GENE AB Human cancers arise from a series of mutations, many of which direct the expression of mutant proteins with altered functions. These aberrant proteins are attractive targets for new therapeutic agents, One such protein is a mutant epidermal growth factor receptor (EGFRvIII) that has an in-frame deletion near the NH2 terminus of its extracellular domain. This protein was first identified in human gliomas, but has also been shown to be present in lung and breast carcinomas. The deletion results in a receptor with constitutive tyrosine kinase activity that enhances the tumorigenicity of glioblastomas irt vivo. The deletion also creates a tumor-specific cell-surface sequence at the deletion junction. Three specific anti-EGFRvIII mAbs have been isolated following immunization with a mixture of a deletion junction synthetic peptide and EGFRvIII as present on cell membranes, We have constructed immunotoxins by conjugating a modified version of Pseudomonas exotoxin A to these mAbs, Immunotoxins were tested on cells that had been transfected with cDNA for the EGFRvIII receptor and expressed receptor protein at 5 x 10(5) receptors/cell. All three immunotoxins were cytotoxic to these cells, with 50% inhibition of protein synthesis occurring in a 15-50 pM range. The immunotoxins specifically targeted EGFRvIII, as their cytotoxicity could be blocked by their respective free antibody. They showed little or no cytotoxicity to cells expressing high levels of normal epidermal growth factor receptors, demonstrating that they are able to discriminate between cells expressing the mutant receptor and those expressing the wild-type receptor, Immunotoxins targeted to mutant epidermal growth factor receptors are promising candidates for further development as tumor cell-specific therapeutic agents. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DUKE COMPREHENS CANC CTR,DURHAM,NC 27710. NR 30 TC 62 Z9 62 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1995 VL 1 IS 8 BP 859 EP 864 PG 6 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300010 PM 9816055 ER PT J AU Prasanna, P Shack, S Wilson, VL Samid, D AF Prasanna, P Shack, S Wilson, VL Samid, D TI Phenylacetate in chemoprevention: In vitro and in vivo suppression of 5-aza-2'-deoxycytidine-induced carcinogenesis SO CLINICAL CANCER RESEARCH LA English DT Article ID FETAL HEMOGLOBIN PRODUCTION; CLINICAL-TRIALS; DNA METHYLATION; PROGRESSION STAGES; CELLS; CANCER; ACID; GENE; 4-PHENYLBUTYRATE; DIFFERENTIATION AB Differentiation inducers selected for their low cytotoxic and genotoxic potential could be of major value in chemoprevention and maintenance therapy, We focus here on phenylacetate, a naturally occurring plasma component recently shown to affect the growth and differentiation of established neoplasms in experimental models, The ability of phenylacetate to prevent carcinogenesis by the chemotherapeutic hypomethylating drug 5-aza-2'-deoxycytidine (5AzadC) was tested in vitro and in mice, Transient exposure of immortalized, but poorly tumorigenic ras-transformed 4C8 fibroblasts to 5AzadC resulted in neoplastic transformation manifested by loss of contact inhibition of growth, acquired invasiveness, and increased tumorigenicity in athymic mice, The latter was associated with elevation in ras expression and a decline in collagen biosynthesis, These profound phenotypic and molecular changes were prevented by a simultaneous treatment with phenylacetate. Protection from 5AzadC carcinogenesis by phenylacetate was: (a) highly efficient despite DNA hypomethylation by both drugs, (b) free of cytotoxic and genotoxic effects, (c) stable after treatment was discontinued, and (d) reproducible in vivo, Whereas athymic mice bearing 4C8 cells developed fibrosarcomas following a single i,p, injection with 5AzadC, tumor development was significantly inhibited by systemic treatment with nontoxic doses of phenylacetate, Phenylacetate and its precursor suitable for oral administration, phenylbutyrate, may thus represent a new class of chemopreventive agents, the efficacy and safety of which should be further evaluated. C1 NCI,CLIN PHARMACOL BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20892. CHILDRENS HOSP,DEPT PATHOL,MOLEC GENET ONCOL LAB,DENVER,CO 80218. NR 41 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1995 VL 1 IS 8 BP 865 EP 871 PG 7 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300011 PM 9816056 ER PT J AU Katayose, D Gudas, J Nguyen, H Srivastava, S Cowan, KH Seth, P AF Katayose, D Gudas, J Nguyen, H Srivastava, S Cowan, KH Seth, P TI Cytotoxic effects of adenovirus-mediated wild-type p53 protein expression in normal and tumor mammary epithelial cells SO CLINICAL CANCER RESEARCH LA English DT Article ID APOPTOSIS; CANCER; GENE; TRANSFORMATION; PROLIFERATION; SUPPRESSION; MUTATIONS; MUTANT; LINE AB To evaluate the effects of the wild-type p53 expression in normal and tumor cells, we have constructed a recombinant adenovirus vector (E1 minus) expressing human wildtype p53 cDNA (AdWTp53). Infection of normal and tumor cells of lung and mammary epithelial origin with AdWTp53 resulted in high levels of wild type p53 expression. Production of p53 protein following infection was dependent on the dose of AdWTp53 with maximum amounts of p53 produced following infection with 50 plaque-forming units/cell, AdWTp53 infection inhibited the growth of all human cell lines studied, However, tumor cells that were null for p53 prior to infection (H-358 and MDA-MB-157) and tumor cells that expressed mutant endogenous p53 protein (MDA-MB-231 and MDA-MB-453) were more sensitive to AdWTp53 cytotoxicity than cells that contained the wild-type p53 (MCF-7, MCF-10, 184B5, and normal mammary epithelial cells), All cells exhibited WAF1/Cip1 mRNA and protein induction following AdWTp53 infection. AdWTp53-induced cytotoxicity of human tumor cell lines expressing mutant p53 was mediated by apoptosis as revealed by nucleosomal DNA fragmentation analysis, No detectable nucleosomal DNA fragmentation was observed following AdWTp53 infection of human cells expressing wild-type p53. These data suggest that endogenous p53 status is a determinant of AdWTp53-mediated cell killing of human tumor cells. C1 NCI,MED BRANCH,MED BREAST CANC SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,CTR PROSTATE DIS RES,BETHESDA,MD 20814. NR 44 TC 118 Z9 119 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1995 VL 1 IS 8 BP 889 EP 897 PG 9 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300014 PM 9816059 ER PT J AU Zeng, ZS Cohen, AM Zhang, ZF StetlerStevenson, W Guillem, JG AF Zeng, ZS Cohen, AM Zhang, ZF StetlerStevenson, W Guillem, JG TI Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph node and distant metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID ERYTHROID-POTENTIATING ACTIVITY; B16-F10 MELANOMA-CELLS; HUMAN COLON CANCER; COLLAGENASE INHIBITOR; DEGRADING METALLOPROTEINASES; MESSENGER-RNA; TUMOR-CELLS; EXPRESSION; TIMP-1; INVASION AB Tissue inhibitor of metalloproteinase (TIMP) inhibits the proteolytic activity of several matrix metalloproteinases centrally involved in tumor invasion and metastases, The purpose of this study was to determine the origin of TIMP-1 mRNA production in both human colorectal cancer (CRC) and metastatic liver lesions as well as define the relationships between TIMP-1 RNA expression and standard clinicopathological variables of CRC, Total cellular RNA, extracted from 56 CRC and 10 liver metastases, were examined by Northern blot hybridization, The mean/normal mucosa fold increase of TIMP-1 RNA was significantly elevated in both CRC (12.1 +/- 1.7) and liver metastases (10.0 +/- 3.6), No relationship was noted between TIMP-1 expression and tumor size, location nor differentiation. Based on lymph node metastases status, significantly higher TIMP-1 RNA levels were found in CRC with metastases than in those without metastases (15.6 +/- 3.3 versus 7.9 +/- 1.3) (P = 0.04), Similarly, TIMP-1 RNA levels were higher in primary CRC with distant metastases than those without distant metastases (17.6 +/- 4.1 versus 9.3 +/- 1.9) (P = 0.04), In situ hybridization localized TIMP-1 mRNA predominantly in tumor stroma within spindle fibroblast-like cells rather than in cancer cells themselves, The correlation between the increased TIMP-1 mRNA level and advanced CRC stage noted in this study reflects a possible growth-promoting function for TIMP-1 in human CRC. C1 MEM SLOAN KETTERING CANC CTR,DEPT SURG,COLORECTAL SERV,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & STAT,EPIDEMIOL SERV,NEW YORK,NY 10021. NCI,DEPT PATHOL,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 41 TC 123 Z9 129 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1995 VL 1 IS 8 BP 899 EP 906 PG 8 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300015 PM 9816060 ER PT J AU Katzenellenbogen, JA Coleman, RE Hawkins, RA Krohn, KA Larson, SM Mendelsohn, J Osborne, CK PiwnicaWorms, D Reba, RC Siegel, BA Welch, MJ Shtern, F AF Katzenellenbogen, JA Coleman, RE Hawkins, RA Krohn, KA Larson, SM Mendelsohn, J Osborne, CK PiwnicaWorms, D Reba, RC Siegel, BA Welch, MJ Shtern, F TI Tumor receptor imaging: Proceedings of the national cancer institute workshop, review of current work, and prospective for further investigations SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID POSITRON EMISSION TOMOGRAPHY; METASTATIC BREAST-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; MULTIDRUG-RESISTANCE; PROGESTERONE-RECEPTOR; ISOLATED HEPATOCYTES; HUMAN NEUROBLASTOMA; ANDROGEN RECEPTOR; P-GLYCOPROTEIN AB In February 1994, the National Cancer Institute held a workshop to evaluate the current and future role of emission tomographic imaging methods, positron emission tomography and single-photon emission computed tomography, in improving the accuracy of cancer diagnosis and the effectiveness of treatment and in elucidating basic aspects of human cancer biology, Reviews covered many of the receptor and transport systems for hormones and growth factors, as well as metabolic changes important in human cancer, and topical presentations reviewed the current status of receptor-based imaging in the most well-characterized systems: somatostatin receptor imaging of neuroendocrine tumors, estrogen receptor imaging of breast cancer, and epidermal growth factor receptor and tumor metabolic imaging, A critical analysis was made of the current research and of new directions for the future development and use of receptor-imaging methods in oncology, In each area, recommendations were made for further investigation, where emerging understanding of tumor cell biology and defined molecular targets might be combined with the methods of radiopharmaceutical design and evaluation, to develop new approaches to critical issues in the diagnosis, staging, and treatment of cancer through tumor receptor imaging. C1 DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT RADIOL,SAN FRANCISCO,CA 94143. MEM SLOAN KETTERING CANC CTR,DEPT MED IMAGING,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,DIV RADIAT SCI,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,DIV NUCL MED,ST LOUIS,MO 63110. UNIV CHICAGO,DEPT RADIOL,CHICAGO,IL 60637. NCI,DIAGNOST IMAGING RES BRANCH,BETHESDA,MD 20852. RP Katzenellenbogen, JA (reprint author), UNIV ILLINOIS,DEPT CHEM,ROGER ADAMS LAB 461,BOX 37,600 S MATHEWS AVE,URBANA,IL 61801, USA. NR 81 TC 20 Z9 21 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1995 VL 1 IS 8 BP 921 EP 932 PG 12 WC Oncology SC Oncology GA TL083 UT WOS:A1995TL08300018 PM 9816063 ER PT J AU GROSS, PA KAPLAN, JE PHAIR, JP MASUR, H WILFERT, CM HOLMES, KK AF GROSS, PA KAPLAN, JE PHAIR, JP MASUR, H WILFERT, CM HOLMES, KK TI INDICATORS FOR ASSESSMENT OF COMPLIANCE WITH QUALITY STANDARDS FOR THE PREVENTION OF OPPORTUNISTIC INFECTIONS IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. NIH,BETHESDA,MD 20892. DUKE UNIV,DURHAM,NC 27706. UNIV WASHINGTON,SEATTLE,WA 98195. RP GROSS, PA (reprint author), HACKENSACK MED CTR,DEPT INTERNAL MED,30 PROSPECT AVE,HACKENSACK,NJ 07601, USA. NR 3 TC 3 Z9 3 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 AUG PY 1995 VL 21 SU 1 BP S138 EP S141 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600026 PM 8547509 ER PT J AU GROSS, PA PHAIR, JP KAPLAN, JE HOLMES, KK MASUR, H AF GROSS, PA PHAIR, JP KAPLAN, JE HOLMES, KK MASUR, H TI QUALITY STANDARD FOR THE ENUMERATION OF CD4(+) LYMPHOCYTES IN ADULTS AND ADOLESCENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MULTICENTER AIDS COHORT; PROPHYLAXIS; TYPE-1 C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. HACKENSACK MED CTR,HACKENSACK,NJ 07604. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NR 7 TC 2 Z9 2 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 AUG PY 1995 VL 21 SU 1 BP S126 EP S127 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600020 PM 8547503 ER PT J AU KAPLAN, JE MASUR, H HOLMES, KK WILFERT, CM SPERLING, R BAKER, SA TRAPNELL, CB FREEDBERG, KA COTTON, D POWDERLY, WG JAFFE, HW LANIER, D SCHRAM, N COOPER, E MAYER, K BLINKHORN, R ELLNER, J ANGULO, J BERKELMAN, R BREIMAN, R BRYAN, R BEUHLER, J CALDWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KELLER, D MARTONE, W MCNEIL, MM MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SCHONBERGER, LB SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M BARR, D TORRES, G STETLER, H GROSS, P ELSADR, W GREAVES, W BARTLETT, J CHAISON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C AF KAPLAN, JE MASUR, H HOLMES, KK WILFERT, CM SPERLING, R BAKER, SA TRAPNELL, CB FREEDBERG, KA COTTON, D POWDERLY, WG JAFFE, HW LANIER, D SCHRAM, N COOPER, E MAYER, K BLINKHORN, R ELLNER, J ANGULO, J BERKELMAN, R BREIMAN, R BRYAN, R BEUHLER, J CALDWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KELLER, D MARTONE, W MCNEIL, MM MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SCHONBERGER, LB SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M BARR, D TORRES, G STETLER, H GROSS, P ELSADR, W GREAVES, W BARTLETT, J CHAISON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C TI USPHS/IDSA GUIDELINES FOR THE PREVENTION OF OPPORTUNISTIC INFECTIONS IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - AN OVERVIEW SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RECOMMENDATIONS; CONSEQUENCES; TUBERCULOSIS; PROPHYLAXIS; PREGNANCY; THERAPY; PEOPLE; TYPE-1; DRUGS; WOMEN C1 NIH, BETHESDA, MD 20892 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. AMER ASSOC PHYSICIANS HUMAN RIGHTS, SAN FRANCISCO, CA USA. AMER FDN AIDS RES, ROCKVILLE, MD USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. BROWN UNIV, PROVIDENCE, RI 02912 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. COUNCIL STATE & TERR EPIDEMIOLGISTS, ATLANTA, GA USA. DALHOUSIE UNIV, HALIFAX, NS, CANADA. DUKE UNIV, DURHAM, NC USA. EMORY UNIV, ATLANTA, GA 30322 USA. US FDA, ROCKVILLE, MD 20857 USA. GAY MENS HLTH CRISIS INC, NEW YORK, NY USA. GEORGIA DEPT HUMAN RESOURCES, ATLANTA, GA USA. HACKENSACK MED CTR, HACKENSACK, NJ 07604 USA. HARLEM HOSP MED CTR, NEW YORK, NY USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HOWARD UNIV, WASHINGTON, DC 20059 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. MARYLAND DEPT HLTH, BALTIMORE, MD USA. MINNESOTA DEPT PUBL HLTH, MINNEAPOLIS, MN USA. MT AUBURN HOSP, CAMBRIDGE, MA USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. NATL ASSOC PERSONS AIDS, WASHINGTON, DC USA. NHLBI, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. NATL MINOR AIDS COUNCIL, WASHINGTON, DC USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. RUSH MED COLL, CHICAGO, IL 60612 USA. SEATTLE KING CTY DEPT HLTH, SEATTLE, WA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. SUNY STONY BROOK, STONY BROOK, NY 11794 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. UNIV ARIZONA, TUCSON, AZ USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV WASHINGTON, ST LOUIS, MO USA. RP KAPLAN, JE (reprint author), CTR DIS CONTROL & PREVENT, DIV HIV AIDS, MAILSTOP G-29, ATLANTA, GA 30333 USA. RI Childs, James/B-4002-2012; mcgowan jr, john/G-5404-2011 NR 56 TC 52 Z9 52 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1995 VL 21 SU 1 BP S12 EP S31 PG 20 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600002 PM 8547500 ER PT J AU KAPLAN, JE MASUR, H HOLMES, KK LANIER, D SCHRAM, N COOPER, E FREEDBERG, KA MAYER, K BLINKHORN, R ELLNER, J ANGULO, F BERKELMAN, R BREIMAN, R BRYAN, R BUEHLER, J CALDWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KELLER, D MARTONE, W MCNEIL, MM MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SCHONBERGER, LB SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M TRAPNELL, CB BARR, D TORRES, G STETLER, H GROSS, P ELSADR, W COTTON, D GREAVES, W BARTLETT, J CHAISSON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M SPERLING, R AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C AF KAPLAN, JE MASUR, H HOLMES, KK LANIER, D SCHRAM, N COOPER, E FREEDBERG, KA MAYER, K BLINKHORN, R ELLNER, J ANGULO, F BERKELMAN, R BREIMAN, R BRYAN, R BUEHLER, J CALDWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KELLER, D MARTONE, W MCNEIL, MM MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SCHONBERGER, LB SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M TRAPNELL, CB BARR, D TORRES, G STETLER, H GROSS, P ELSADR, W COTTON, D GREAVES, W BARTLETT, J CHAISSON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M SPERLING, R AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C TI USPHS/IDSA GUIDELINES FOR THE PREVENTION OF OPPORTUNISTIC INFECTIONS IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - DISEASE-SPECIFIC RECOMMENDATIONS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 UNIV WASHINGTON, SEATTLE, WA 98195 USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. AMER ASSOC PHYSICIANS HUMAN RIGHTS, SAN FRANCISCO, CA USA. AMER FDN AIDS RES, ROCKVILLE, MD USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. BROWN UNIV, PROVIDENCE, RI 02912 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. COUNCIL STATE & TERR EPIDEMIOLOGISTS, ATLANTA, GA USA. DALHOUSIE UNIV, HALIFAX, NS B3H 3J5, CANADA. DUKE UNIV, DURHAM, NC 27706 USA. EMORY UNIV, ATLANTA, GA 30322 USA. US FDA, ROCKVILLE, MD 20857 USA. GAY MENS HLTH CRISIS INC, NEW YORK, NY USA. GEORGIA DEPT HUMAN RESOURCES, ATLANTA, GA USA. HACKENSACK MED CTR, HACKENSACK, NJ 07604 USA. HARLEM HOSP MED CTR, NEW YORK, NY USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HOWARD UNIV, WASHINGTON, DC 20059 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. MINNESOTA DEPT PUBL HLTH, MINNEAPOLIS, MN USA. MT AUBURN HOSP, CAMBRIDGE, MA USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. NATL ASSOC PERSONS AIDS, WASHINGTON, DC USA. NHLBI, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. RUSH MED COLL, CHICAGO, IL 60612 USA. SEATTLE KING CTY DEPT HLTH, SEATTLE, WA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. SUNY STONY BROOK, STONY BROOK, NY 11794 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. UNIV ARIZONA, TUCSON, AZ 85721 USA. UNIV SAN FRANCISCO, SAN FRANCISCO, CA 94117 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV SO CALIF, LOS ANGELES, CA 90089 USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. MARYLAND DEPT HLTH, BALTIMORE, MD USA. NATL MINOR AIDS COUNCIL, WASHINGTON, DC USA. RP KAPLAN, JE (reprint author), CTR DIS CONTROL & PREVENT, DIV HIV AIDS, MAILSTOP G-29, ATLANTA, GA 30333 USA. RI Childs, James/B-4002-2012; mcgowan jr, john/G-5404-2011 NR 8 TC 3 Z9 3 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1995 VL 21 SU 1 BP S32 EP S43 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600003 ER PT J AU KAPLAN, JE MASUR, H HOLMES, KK MCNEIL, MM SCHONBERGER, LB NAVIN, TR HANSON, DL GROSS, PA JAFFE, HW LANIER, D SCHRAM, N COOPER, E FREEDBERG, KA MAYER, K BLINKHORN, R ELLNER, J ANGULO, F BERKELMAN, R BREIMAN, R BRYAN, R BUEHLER, J CLADWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KAPLAN, JE KELLER, D MARTONE, W MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M TRAPNELL, CB BARR, D TORRES, G STETLER, H GROSS, P ELSADAR, W COTTON, D GREAVES, W BARTLETT, J CHAISSON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M SPERLING, R AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C AF KAPLAN, JE MASUR, H HOLMES, KK MCNEIL, MM SCHONBERGER, LB NAVIN, TR HANSON, DL GROSS, PA JAFFE, HW LANIER, D SCHRAM, N COOPER, E FREEDBERG, KA MAYER, K BLINKHORN, R ELLNER, J ANGULO, F BERKELMAN, R BREIMAN, R BRYAN, R BUEHLER, J CLADWELL, B CASTRO, K CHILDS, JE CHU, S CIESIELSKI, C DROTMAN, DP EDLIN, B ELLERBROCK, T FLEMING, P GEITER, L HAJJEH, R HANSON, D HOLMBERG, S HUGHES, J JAFFE, H JONES, J JURANEK, D KAPLAN, JE KELLER, D MARTONE, W MILLER, B NAVIN, T NESLUND, V OSTROFF, S PELLETT, PE PINNER, R REEF, S REEVES, WC REGNERY, R RICHARDS, F ROGERS, M SIMONDS, RJ SIMONE, P SMITH, D SOLOMON, S SPIEGEL, R STEWART, J SWERDLOW, D VERNON, S WARD, J NEAL, J SCHLECH, W WILFERT, C HORSBURGH, R MCGOWAN, J RIMLAND, D GOLDBERGER, M TRAPNELL, CB BARR, D TORRES, G STETLER, H GROSS, P ELSADAR, W COTTON, D GREAVES, W BARTLETT, J CHAISSON, R FEINBERG, J QUINN, T HORMAN, J MACDONALD, K WILSON, M SPERLING, R AVANDANO, A BAKER, AC KALICA, A KOVACS, J POLIS, M SCHNITTMAN, S NELSON, C PHAIR, J BENSON, C WOOD, B HUGHES, W LUFT, B HYSLOP, N WHITLEY, R AMPEL, N DREW, WL KOEHLER, J WOFSY, C TI USPHS/IDSA GUIDELINES FOR THE PREVENTION OF OPPORTUNISTIC INFECTIONS IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - INTRODUCTION SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID IMMUNE-DEFICIENCY-SYNDROME; MYCOBACTERIUM-AVIUM COMPLEX; PNEUMOCYSTIS-CARINII PNEUMONIA; HIV-SEROPOSITIVE PATIENTS; HYDROPHILA-ASSOCIATED COLITIS; CENTRAL-NERVOUS-SYSTEM; ACQUIRED-IMMUNODEFICIENCY; AIDS PATIENT; TRIMETHOPRIM-SULFAMETHOXAZOLE; PULMONARY CRYPTOCOCCOSIS C1 NIH, BETHESDA, MD 20892 USA. WASHINGTON UNIV, SEATTLE, WA USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. AMER ASSOC PHYSICIANS HUMAN RIGHTS, SAN FRANCISCO, CA USA. AMER FDN AIDS RES, ROCKVILLE, MD USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. BROWN UNIV, PROVIDENCE, RI 02912 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. COUNCIL STATE & TERR EPIDEMIOLOGISTS, ATLANTA, GA USA. DALHOUSIE UNIV, HALIFAX, NS, CANADA. DUKE UNIV, DURHAM, NC USA. EMORY UNIV, ATLANTA, GA 30322 USA. US FDA, ROCKVILLE, MD 20857 USA. GAY MENS HLTH CRISIS INC, NEW YORK, NY USA. GEORGIA DEPT HUMAN RESOURCES, ATLANTA, GA USA. HACKENSACK MED CTR, HACKENSACK, NJ 07604 USA. HARLEM HOSP MED CTR, NEW YORK, NY USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HOWARD UNIV, WASHINGTON, DC 20059 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. MARYLAND DEPT HLTH, BALTIMORE, MD USA. MINNESOTA DEPT PUBL HLTH, MINNEAPOLIS, MN USA. MT AUBURN HOSP, CAMBRIDGE, MA 02238 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. NATL ASSOC PERSONS AIDS, WASHINGTON, DC USA. NHLBI, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. NATL MINOR AIDS COUNCIL, WASHINGTON, DC USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. RUSH MED COLL, CHICAGO, IL 60612 USA. SEATTLE KING CTY DEPT HLTH, SEATTLE, WA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. SUNY STONY BROOK, STONY BROOK, NY 11794 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. UNIV ARIZONA, TUCSON, AZ USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV WASHINGTON, ST LOUIS, MO USA. RP KAPLAN, JE (reprint author), CTR DIS CONTROL & PREVENT, NATL IMMUNIZATION PROGRAM, DIV HIV AIDS, MAILSTOP G-29, ATLANTA, GA 30333 USA. RI Childs, James/B-4002-2012 NR 172 TC 42 Z9 42 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1995 VL 21 SU 1 BP S1 EP S11 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600001 PM 8547495 ER PT J AU PHAIR, JP GROSS, PA KAPLAN, JE MASUR, H HOLMES, KK WILFERT, CM MARTONE, WJ CASTRO, KG AF PHAIR, JP GROSS, PA KAPLAN, JE MASUR, H HOLMES, KK WILFERT, CM MARTONE, WJ CASTRO, KG TI QUALITY STANDARD FOR THE IDENTIFICATION AND TREATMENT OF PERSONS COINFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS AND MYCOBACTERIUM-TUBERCULOSIS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 HACKENSACK MED CTR,HACKENSACK,NJ 07604. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. DUKE UNIV,DURHAM,NC 27706. RP PHAIR, JP (reprint author), NORTHWESTERN UNIV,SCH MED,680 N LAKE SHORE DR,SUITE 1106,CHICAGO,IL 60611, USA. NR 5 TC 0 Z9 0 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 AUG PY 1995 VL 21 SU 1 BP S130 EP S131 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600022 PM 8547505 ER PT J AU PHAIR, JP MASUR, H GROSS, PA HOLMES, KK KAPLAN, JE AF PHAIR, JP MASUR, H GROSS, PA HOLMES, KK KAPLAN, JE TI QUALITY STANDARD FOR THE PROPHYLAXIS OF PNEUMOCYSTIS-CARINII PNEUMONIA IN ADULTS AND ADOLESCENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 NIH,BETHESDA,MD 20892. HACKENSACK MED CTR,HACKENSACK,NJ 07604. UNIV WASHINGTON,SEATTLE,WA 98195. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. RP PHAIR, JP (reprint author), NORTHWESTERN UNIV,SCH MED,680 N LAKE SHORE DR,SUITE 1106,CHICAGO,IL 60611, USA. NR 8 TC 1 Z9 1 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 AUG PY 1995 VL 21 SU 1 BP S128 EP S129 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600021 PM 8547504 ER PT J AU PHAIR, JP GROSS, PA KAPLAN, JE MASUR, H HOLMES, KK WILFERT, CM AF PHAIR, JP GROSS, PA KAPLAN, JE MASUR, H HOLMES, KK WILFERT, CM TI QUALITY STANDARDS FOR PREVENTING OPPORTUNISTIC INFECTIONS RELATED TO HUMAN-IMMUNODEFICIENCY-VIRUS AND THEIR IMPLEMENTATION SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 HACKENSACK MED CTR,HACKENSACK,NJ 07604. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. DUKE UNIV,DURHAM,NC 27706. RP PHAIR, JP (reprint author), NORTHWESTERN UNIV,SCH MED,680 N LAKE SHORE DR,SUITE 1106,CHICAGO,IL 60611, USA. NR 5 TC 0 Z9 0 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 AUG PY 1995 VL 21 SU 1 BP S125 EP S125 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600019 PM 8547502 ER PT J AU RICHARDS, FO KOVACS, JA LUFT, BJ AF RICHARDS, FO KOVACS, JA LUFT, BJ TI PREVENTING TOXOPLASMIC ENCEPHALITIS IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; CENTRAL-NERVOUS-SYSTEM; WEEKLY DAPSONE-PYRIMETHAMINE; AEROSOLIZED PENTAMIDINE; CEREBRAL TOXOPLASMOSIS; AIDS PATIENTS; TRIMETHOPRIM-SULFAMETHOXAZOLE; PRIMARY PROPHYLAXIS; COTRIMOXAZOLE; THERAPY AB Toxoplasmic encephalitis CTE) is the second most common AIDS-related opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS who are seropositive for antibodies to Toxoplasma gondii and have CD4(+) T lymphocyte counts of <100/mm(3), Primary toxoplasmic infection usually is acquired by ingestion of T. gondii oocysts from soil contaminated by cat feces or by ingestion of tissue cysts present in undercooked red meats. In patients with AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that remained latent after the primary infection. Detection of IgG antibodies to Toxoplasma indicates prior infection and the possible presence of tissue cysts and, thus, risk for developing TE, A regimen of trimethoprim-sulfamethoxa-zole or dapsone plus pyrimethamine with leucovorin is recommended for persons infected with the human immunodeficiency virus (HIV) and who are seropositive for IgG to Toxoplasma after their CD4(+) T lymphocyte counts fall to <100/mm(3), HIV-infected persons who are seronegative for IgG to Toxoplasma should be counseled to protect themselves from primary toxoplasmic infection by eating only well-cooked meats and washing their hands after outdoor activities involving soil contact; if they have a cat, they should feed it only commercial or well-cooked foods, keep it indoors, and make sure that the litter box is changed daily, HN-infected persons who are Toxoplasma seropositive may also be advised about these preventive behavioral practices. C1 NIH, CTR CLIN, DEPT CRIT CARE MED, BETHESDA, MD 20892 USA. SUNY STONY BROOK, DEPT MED, STONY BROOK, NY 11794 USA. RP RICHARDS, FO (reprint author), CTR DIS CONTROL & PREVENT, NATL CTR INFECT DIS, EPIDEMIOL BRANCH, DIV PARASIT DIS, ATLANTA, GA 30333 USA. NR 44 TC 38 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1995 VL 21 SU 1 BP S49 EP S56 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600005 PM 8547512 ER PT J AU WILFERT, CM GROSS, PA KAPLAN, JE HOLMES, KK MASUR, H PHAIR, JP SIMONDS, RJ AF WILFERT, CM GROSS, PA KAPLAN, JE HOLMES, KK MASUR, H PHAIR, JP SIMONDS, RJ TI QUALITY STANDARD FOR THE ENUMERATION OF CD4(+) LYMPHOCYTES IN INFANTS AND CHILDREN EXPOSED TO OR INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 HACKENSACK MED CTR,HACKENSACK,NJ 07604. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. UNIV WASHINGTON,SEATTLE,WA 98195. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. NIH,BETHESDA,MD 20892. RP WILFERT, CM (reprint author), DUKE UNIV,MED CTR,DEPT PEDIAT,BOX 2951,DURHAM,NC 27710, USA. NR 11 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 AUG PY 1995 VL 21 SU 1 BP S134 EP S135 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600024 PM 8547507 ER PT J AU WILFERT, CM KAPLAN, JE GROSS, PA MASUR, H HOLMES, KK PHAIR, JP AF WILFERT, CM KAPLAN, JE GROSS, PA MASUR, H HOLMES, KK PHAIR, JP TI QUALITY STANDARD FOR THE IMMUNIZATION OF INFANTS AND CHILDREN BORN TO WOMEN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. HACKENSACK MED CTR,HACKENSACK,NJ 07604. NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP WILFERT, CM (reprint author), DUKE UNIV,MED CTR,DEPT PEDIAT,BOX 2951,DURHAM,NC 27710, USA. NR 5 TC 3 Z9 3 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 AUG PY 1995 VL 21 SU 1 BP S136 EP S137 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600025 PM 8547508 ER PT J AU WILFERT, CM MASUR, H GROSS, PA KAPLAN, JE HOLMES, KK PHAIR, JP SIMONDS, RJ AF WILFERT, CM MASUR, H GROSS, PA KAPLAN, JE HOLMES, KK PHAIR, JP SIMONDS, RJ TI QUALITY STANDARD FOR THE PROPHYLAXIS OF PNEUMOCYSTIS-CARINII PNEUMONIA IN INFANTS AND CHILDREN BORN TO WOMEN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 NIH,BETHESDA,MD 20892. HACKENSACK MED CTR,HACKENSACK,NJ 07604. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. UNIV WASHINGTON,SEATTLE,WA 98195. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP WILFERT, CM (reprint author), DUKE UNIV,MED CTR,DEPT PEDIAT,BOX 2951,DURHAM,NC 27710, USA. NR 5 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 AUG PY 1995 VL 21 SU 1 BP S132 EP S133 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RN616 UT WOS:A1995RN61600023 PM 8547506 ER PT J AU MAX, MB BYASSMITH, MG GRACELY, RH BENNETT, GJ AF MAX, MB BYASSMITH, MG GRACELY, RH BENNETT, GJ TI INTRAVENOUS-INFUSION OF THE NMDA ANTAGONIST, KETAMINE, IN CHRONIC POSTTRAUMATIC PAIN WITH ALLODYNIA - A DOUBLE-BLIND COMPARISON TO ALFENTANIL AND PLACEBO SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE PAIN; ANALGESIA; RANDOMIZED CLINICAL TRIALS; NMDA RECEPTOR ANTAGONISTS; REFLEX SYMPATHETIC DYSTROPHY ID MECHANISMS AB NMDA antagonists and opioids relieve experimentally produced hyperalgesia in animals and humans, presumably by attenuating a heightened central nervous system response to afferent input, A few small studies in patients have suggested that intravenous boluses or rapid infusions of the N-methyl-D-aspartate (NMDA) antagonist ketamine relieve some neuropathic pains but also produce disturbances of cognition and mood, In a randomized, double-blind, crossover trial, we treated eight patients with chronic posttraumatic pain and widespread mechanical allodynia with 2-h intravenous infusions of the NMDA antagonist ketamine (mean dose, 58 mg), the opioid mu-receptor agonist alfentanil (mean dose, 11 mg), and placebo. The patients were selected because extensive sensory testing suggested that altered central processing contributed to their symptoms. The slow rate of drug infusion was chosen to see if pain relief would precede dose-limiting side effects. Means of the peak effect scores achieved during the 2-h infusion were for pain relief: ketamine, 65%, alfentanil, 46%, and placebo, 22% (p < 0.01 for ketamine and p = 0.08 for alfentanil, each compared to placebo); and for relief of allodynia: ketamine, 71%, alfentanil, 57%, and placebo, 21% (p < 0.01 for both ketamine and alfentanil). Appreciable symptomatic relief developed only after the onset of unpleasant drug side effects. After the infusion was stopped, pain relief disappeared before the side effects resolved, We conclude that NMDA antagonists may have promise for the treatment of neuropathic pain, but strategies are needed to improve their therapeutic ratio, such as intrathecal administration or systemic treatment with more selective drugs. RP MAX, MB (reprint author), NIDR,PAIN RES CLIN,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 10,ROOM 3C-405,10 CTR DR MSC 1258,BETHESDA,MD 20892, USA. NR 21 TC 128 Z9 129 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD AUG PY 1995 VL 18 IS 4 BP 360 EP 368 DI 10.1097/00002826-199508000-00008 PG 9 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA RL554 UT WOS:A1995RL55400008 PM 8665549 ER PT J AU ROSSE, RB KENDRICK, K TSUI, LC FAYMCCARTHY, M COLLINS, JP ROSENBERG, P WYATT, RJ DEUTSCH, SI AF ROSSE, RB KENDRICK, K TSUI, LC FAYMCCARTHY, M COLLINS, JP ROSENBERG, P WYATT, RJ DEUTSCH, SI TI FAMOTIDINE ADJUNCTIVE PHARMACOTHERAPY OF SCHIZOPHRENIA - A CASE-REPORT SO CLINICAL NEUROPHARMACOLOGY LA English DT Note DE FAMOTIDINE; HISTAMINE; H2 RECEPTOR; H2 ANTAGONIST; SCHIZOPHRENIA ID NEGATIVE SYMPTOMS; SLEEP; DEFINITION; SYSTEMS AB Recent reports suggest some utility for famotidine, a histamine type 2 (H2) antagonist, in the treatment of schizophrenia. The current report describes a treatment-resistant patient with chronic undifferentiated schizophrenia whose most dramatic symptomatic improvements were temporally related to the open-label addition of famotidine (40-100 mg/day) to conventional neuroleptic treatment (molindone 150-200 mg/day) over the course of similar to 10 months. During one 2-week interval, his symptoms were controlled with famotidine (40 mg/day) alone. The case suggests that some adjuvant efficacy exists for famotidine in at least some patients with schizophrenia, Placebo-controlled trials are needed to more fully evaluate the utility of famoditine in the treatment of schizophrenia. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RI Tsui, Lap-chee/A-1081-2010 NR 22 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD AUG PY 1995 VL 18 IS 4 BP 369 EP 374 DI 10.1097/00002826-199508000-00009 PG 6 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA RL554 UT WOS:A1995RL55400009 PM 8665550 ER PT J AU GREEN, SB AF GREEN, SB TI BYAR,DAVID - AN ACCIDENTAL CAREER SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material RP GREEN, SB (reprint author), NCI,EXECUT PLAZA N,ROOM 344,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1995 VL 16 IS 4 BP 189 EP 190 DI 10.1016/S0197-2456(95)80002-6 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RN178 UT WOS:A1995RN17800001 PM 7587205 ER PT J AU GAIL, MH AF GAIL, MH TI BYAR,DAVE CONTRIBUTION TO EPIDEMIOLOGY SO CONTROLLED CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Scientific Workshop on David Byar - An Accidental Career CY NOV 07-08, 1991 CL BETHESDA, MD ID RANDOMIZED CLINICAL-TRIALS; HEART-TRANSPLANT DATA; 2X2 CONTINGENCY-TABLES; HELPER LYMPHOCYTES-T; SCORE TESTS; COVARIATE-INFORMATION; REGRESSION-MODELS; ATTRIBUTABLE RISK; HOMOSEXUAL MEN; BREAST-CANCER AB Some of Dave Byar's personal qualities and his scientific approach are described. His work on substantive epidemiologic projects is mentioned briefly. There follows a review of his work on theoretical issues, including extentions of the Mantel-Haenszel procedure and other contingency table methods, confounding, and estimation of attributable and absolute risk from case-control data. RP GAIL, MH (reprint author), NCI,BIOSTAT BRANCH,EPN-431,ROCKVILLE,MD 20892, USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1995 VL 16 IS 4 BP 230 EP 248 DI 10.1016/S0197-2456(95)80009-3 PG 19 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RN178 UT WOS:A1995RN17800008 PM 7587212 ER PT J AU BUSH, TL ESPELAND, MA MEBANESIMS, I AF BUSH, TL ESPELAND, MA MEBANESIMS, I TI THE POSTMENOPAUSAL ESTROGEN PROGESTIN INTERVENTIONS (PEPI) TRIAL - OVERVIEW SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; DUAL-PHOTON-ABSORPTIOMETRY; CARDIOVASCULAR-DISEASE; REPLACEMENT THERAPY; UNITED-STATES; FOLLOW-UP; ORAL-CONTRACEPTIVES; CLINICAL-TRIALS C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. NHLBI,DIV HEART & VASC DIS,LIPID METAB & ATHEROGENESIS BRANCH,BETHESDA,MD 20892. NR 111 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1995 VL 16 IS 4 SU S BP S1 EP S2 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RN612 UT WOS:A1995RN61200001 PM 7587216 ER PT J AU ESPELAND, MA BUSH, TL MEBANESIMS, I STEFANICK, ML JOHNSON, S SHERWIN, R WACLAWIW, M AF ESPELAND, MA BUSH, TL MEBANESIMS, I STEFANICK, ML JOHNSON, S SHERWIN, R WACLAWIW, M TI RATIONALE, DESIGN, AND CONDUCT OF THE PEPI TRIAL SO CONTROLLED CLINICAL TRIALS LA English DT Article C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. STANFORD UNIV,STANFORD CTR RES DIS PREVENT,PALO ALTO,CA 94304. UNIV IOWA HOSP & CLIN,DEPT OBSTET & GYNECOL,IOWA CITY,IA 52242. UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NHLBI,DIV HEART & VASC DIS,LIPID METAB & ATHEROGENESIS BRANCH,BETHESDA,MD 20892. RP ESPELAND, MA (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103, USA. NR 0 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1995 VL 16 IS 4 SU S BP S3 EP S19 DI 10.1016/0197-2456(94)00033-Y PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RN612 UT WOS:A1995RN61200002 PM 7587218 ER PT J AU JOHNSON, S MEBANESIMS, I HOGAN, PE STOY, DB AF JOHNSON, S MEBANESIMS, I HOGAN, PE STOY, DB TI RECRUITMENT OF POSTMENOPAUSAL WOMEN IN THE PEPI TRIAL SO CONTROLLED CLINICAL TRIALS LA English DT Article C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. GEORGE WASHINGTON UNIV,LIPID RES CLIN,WASHINGTON,DC. NHLBI,DIV HEART & VASC DIS,LIPID METAB & ATHEROGENESIS BRANCH,BETHESDA,MD 20892. RP JOHNSON, S (reprint author), UNIV IOWA HOSP & CLIN,DEPT OBSTET & GYNECOL,IOWA CITY,IA 52242, USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1995 VL 16 IS 4 SU S BP S20 EP S35 DI 10.1016/0197-2456(94)00111-F PG 16 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RN612 UT WOS:A1995RN61200003 PM 7587217 ER PT J AU WOOD, PD KESSLER, G LIPPEL, K STEFANICK, ML WASILAUSKAS, CH WELLS, HB AF WOOD, PD KESSLER, G LIPPEL, K STEFANICK, ML WASILAUSKAS, CH WELLS, HB TI PHYSICAL AND LABORATORY MEASUREMENTS IN THE PEPI TRIAL SO CONTROLLED CLINICAL TRIALS LA English DT Article C1 WASHINGTON UNIV,DEPT MED,ST LOUIS,MO. NHLBI,DIV HEART & VASC DIS,LIPID METAB & ATHEROGENESIS BRANCH,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. RP WOOD, PD (reprint author), STANFORD UNIV,STANFORD CTR RES DIS PREVENT,PALO ALTO,CA 94304, USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1995 VL 16 IS 4 SU S BP S36 EP S53 DI 10.1016/0197-2456(95)96882-C PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA RN612 UT WOS:A1995RN61200004 PM 7587219 ER PT J AU MARTIN, SE AF MARTIN, SE TI A CROSS-BURNING IS NOT JUST AN ARSON - POLICE SOCIAL CONSTRUCTION OF HATE CRIMES IN BALTIMORE COUNTY SO CRIMINOLOGY LA English DT Article; Proceedings Paper CT 1990 Annual Meeting of the Law-and-Society-Association CY MAY 31-JUN 03, 1990 CL BERKELEY, CA SP Law & Soc Assoc ID VIOLENCE AB Growing public concern over racial and ethnic conflict and a perceived increase in hate crimes during the 1980s have led to legislation expanding the scope of the law and the severity of punishment for such offenses and to police-initiated efforts to focus attention on hate crimes. Although a number of critiques have examined the legislative approach, little attention has been devoted to the police response. This article examines the rationale for a police initiative in addressing hate crimes; the characteristics of incidents labeled as such in one jurisdiction, Baltimore County, Maryland; and some of the problems in defining, identifying, and verifying bias motivation. Because about 40% of the offenses initially considered by the Baltimore County Police Department to be motivated by racial, religious, or ethnic (RRE) prejudice subsequently are not verified as RRE motivated, a closer examination of all such cases permits insight into the social construction of ''bias motivation'' and related issues raised by a police hate-crime program. These include determining what forms of bias are eligible for special responses; identifying bias motivation; weighing the victim's perception of the event; determining the line between criminal and noncriminal incidents; and adopting consistent standards for verifying ambiguous events. RP MARTIN, SE (reprint author), NIAAA,PREVENT RES BRANCH,ROCKVILLE,MD 20852, USA. NR 33 TC 41 Z9 41 U1 0 U2 4 PU AMER SOC CRIMINOLOGY PI COLUMBUS PA 1314 KINNEAR RD, COLUMBUS, OH 43212 SN 0011-1384 J9 CRIMINOLOGY JI Criminololgy PD AUG PY 1995 VL 33 IS 3 BP 303 EP 326 DI 10.1111/j.1745-9125.1995.tb01180.x PG 24 WC Criminology & Penology SC Criminology & Penology GA RL928 UT WOS:A1995RL92800001 ER PT J AU BRADY, G BILLIA, F KNOX, J HOANG, T KIRSCH, IR VOURA, EB HAWLEY, RG CUMMING, R BUCHWALD, M SIMINOVITCH, K MIYAMOTO, N BOEHMELT, G ISCOVE, NN AF BRADY, G BILLIA, F KNOX, J HOANG, T KIRSCH, IR VOURA, EB HAWLEY, RG CUMMING, R BUCHWALD, M SIMINOVITCH, K MIYAMOTO, N BOEHMELT, G ISCOVE, NN TI ANALYSIS OF GENE-EXPRESSION IN A COMPLEX DIFFERENTIATION HIERARCHY BY GLOBAL AMPLIFICATION OF CDNA FROM SINGLE CELLS SO CURRENT BIOLOGY LA English DT Article ID ACTIN MESSENGER-RNAS; PROTEIN-TYROSINE KINASES; GAMMA-ACTIN; BETA-ACTIN; MAST-CELLS; MYB GENE; CLONING; SEQUENCE; DNA; IDENTIFICATION AB Background: Many differentiating tissues contain progenitor cells that differ in their commitment states but cannot be readily distinguished or segregated. Molecular analysis is therefore restricted to mixed populations or cell lines which may also be heterogeneous, and the critical differences in gene expression that might determine divergent development are obscured. In this study, we combined global amplification of mRNA transcripts in single cells with identification of the developmental potential of processed cells on the basis of the fates of their sibling cells from clonal starts. Results: We analyzed clones of from four to eight hemopoietic precursor cells which had a variety of differentiative potentials; sibling cells generally each formed clones of identical composition in secondary culture. Globally amplified cDNA was prepared from individual precursors whose developmental potential was identified by tracking sibling fates. Further cDNA samples were prepared from terminally maturing, homogeneous hemopoietic cell populations. Together, the samples represented 16 positions in the hemopoietic developmental hierarchy. Expression patterns in the sample set were determined for 29 genes known to be involved in hemopoietic cell growth, differentiation or function. The cDNAs from a bipotent erythroid/megakaryocyte precursor and a bipotent neutrophil/macrophage precursor were subtractively hybridized, yielding numerous differentially expressed cDNA clones. Hybridization of such clones to the entire precursor sample set identified transcripts with consistent patterns of differential expression in the precursor hierarchy. Conclusions: Tracking of sibling fates reliably identifies the differentiative potential of a single cell taken for PCR analysis, and demonstrates the existence of a variety of distinct and stable states of differentiative commitment. Global amplification of cDNA from single precursor cells, identified by sibling fates, yields a true representation of lineage- and stage-specific gene expression, as confirmed by hybridization to a broad panel of probes. The results provide the first expression mapping of these genes that distinguishes between progenitors in different commitment states, generate new insights and predictions relevant to mechanism, and introduce a powerful set of tools for unravelling the genetic basis of lineage divergence. C1 UNIV TORONTO,ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M4X 1K9,CANADA. UNIV MONTREAL,DEPT PHARMACOL,CLIN RES INST MONTREAL,MONTREAL,PQ H2W 1R7,CANADA. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. UNIV TORONTO,SUNNYBROOK HLTH SCI CTR,DEPT MED BIOPHYS,TORONTO,ON M4N 3M5,CANADA. UNIV TORONTO,HOSP SICK CHILDREN,RES INST,DEPT MOLEC & MED GENET,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,SAMUEL LUNENFELD RES INST,DEPT MED,TORONTO,ON M5G 1X5,CANADA. RI Siminovitch, Katherine/K-1475-2013; Cumming, Robert/G-2185-2010 NR 66 TC 145 Z9 151 U1 0 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 AUG 1 PY 1995 VL 5 IS 8 BP 909 EP 922 DI 10.1016/S0960-9822(95)00181-3 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RN569 UT WOS:A1995RN56900020 PM 7583149 ER PT J AU SHER, A AHMED, R AF SHER, A AHMED, R TI REGULATION OF INNATE AND ADAPTIVE RESPONSES TO INFECTION - NEW AVENUES AND ANGLES SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 EMORY UNIV,SCH MED,GEORGIA VACCINE CTR,DEPT MICROBIOL & IMMUNOL,ATLANTA,GA 30322. RP SHER, A (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1995 VL 7 IS 4 BP 471 EP 473 DI 10.1016/0952-7915(95)80090-5 PG 3 WC Immunology SC Immunology GA RV081 UT WOS:A1995RV08100007 ER PT J AU JONES, B PASCOPELLA, L FALKOW, S AF JONES, B PASCOPELLA, L FALKOW, S TI ENTRY OF MICROBES INTO THE HOST - USING M-CELLS TO BREAK THE MUCOSAL BARRIER SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID INTESTINAL M-CELLS; COLI STRAIN RDEC-1; SALMONELLA-TYPHIMURIUM; EPITHELIAL-CELLS; PEYERS PATCHES; MOLECULAR CHARACTERIZATION; LYMPHOID FOLLICLES; SHIGELLA-FLEXNERI; VIBRIO-CHOLERAE; IDENTIFICATION AB Enteric microbial pathogens interact with the gut epithelium to establish infection. Recently, it has become clear that many microorganisms that colonize or traverse the intestinal mucosa do so via the specialized M cells. Recent work has shown that Shigella flexneri and Salmonella typhimurium specifically target M cells to initiate infection of the host. C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. RP JONES, B (reprint author), UNIV IOWA,SCH MED,DEPT MICROBIOL,IOWA CITY,IA 52242, USA. FU NIAID NIH HHS [AI-26195]; NIDDK NIH HHS [DK38707] NR 46 TC 44 Z9 45 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1995 VL 7 IS 4 BP 474 EP 478 DI 10.1016/0952-7915(95)80091-3 PG 5 WC Immunology SC Immunology GA RV081 UT WOS:A1995RV08100008 PM 7495510 ER PT J AU WYNN, TA CHEEVER, AW AF WYNN, TA CHEEVER, AW TI CYTOKINE REGULATION OF GRANULOMA-FORMATION IN SCHISTOSOMIASIS SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MANSONI-INFECTED MICE; INTERFERON-GAMMA-PRODUCTION; CELL STIMULATORY FACTOR; MURINE SCHISTOSOMIASIS; IFN-GAMMA; T-CELLS; IN-VIVO; IMMUNE-RESPONSES; DOWN-REGULATION; MESSENGER-RNA AB Granuloma induced by the schistosome egg is an inflammatory reaction that is tightly controlled by the interaction of T-helper cell type 1 (Th1) and Th2 cytokines produced locally. Studies focussing on the immunoregulation of the response have yielded numerous insights into the cytokine cascade that controls the formation of the lesions. It is dear from current data that the Th2 cytokines play a primary role in granuloma formation, whereas the Th1-associated lymphokine interferon-gamma acts as an endogenous down regulator of the response. Through recent advances, it may now be possible to design effective cytokine-based vaccination strategies that will suppress the tissue pathology associated with this helminth infection. C1 NIAID,PARASIT DIS LAB,HOST PARASITE RELAT SECT,BETHESDA,MD 20892. RP WYNN, TA (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,BLDG 4-126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 61 TC 124 Z9 124 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1995 VL 7 IS 4 BP 505 EP 511 DI 10.1016/0952-7915(95)80095-6 PG 7 WC Immunology SC Immunology GA RV081 UT WOS:A1995RV08100012 PM 7495514 ER PT J AU CHERNOMORDIK, LV ZIMMERBERG, J AF CHERNOMORDIK, LV ZIMMERBERG, J TI BENDING MEMBRANES TO THE TASK - STRUCTURAL INTERMEDIATES IN BILAYER FUSION SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID INFLUENZA HEMAGGLUTININ; PHASE-TRANSITION; FATTY-ACIDS; MECHANISMS; ENERGETICS; PROTEINS; VESICLES AB Merger of lipid bilayers plays a central role in diverse biological fusion reactions. Recent studies suggest that different membrane fusion systems, including fusion of purely lipid bilayers, involve formation of similar stalk-type intermediates - highly bent (net negative curvature) and transient lipidic connections between fusing membranes. RP CHERNOMORDIK, LV (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 10D14,10 CTR DR MSC 1855,BETHESDA,MD 20892, USA. NR 67 TC 117 Z9 118 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD AUG PY 1995 VL 5 IS 4 BP 541 EP 547 DI 10.1016/0959-440X(95)80041-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV272 UT WOS:A1995RV27200016 PM 8528771 ER PT J AU CROSS, JC FLANNERY, ML BLANAR, MA STEINGRIMSSON, E JENKINS, NA COPELAND, NG RUTTER, WJ WERB, Z AF CROSS, JC FLANNERY, ML BLANAR, MA STEINGRIMSSON, E JENKINS, NA COPELAND, NG RUTTER, WJ WERB, Z TI HXT ENCODES A BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR THAT REGULATES TROPHOBLAST CELL-DEVELOPMENT SO DEVELOPMENT LA English DT Article DE TROPHOBLAST; PLACENTA; TRANSCRIPTION; HELIX-LOOP-HELIX; HXT; MOUSE; RAT ID CHROMOSOMAL LOCALIZATION; EMBRYONIC-DEVELOPMENT; GENE-EXPRESSION; DNA-BINDING; MOUSE; MURINE; ENHANCER; DROSOPHILA; PROTEIN; DIFFERENTIATION AB Trophoblast cells are the first lineage to form in the mammalian conceptus and mediate the process of implantation, We report the cloning of a basic helix-loop-helis (bHLH) transcription factor gene, Hxt, that is expressed in early trophoblast and in differentiated giant cells, A separate gene, Mcd, encodes a related protein that is expressed in maternal deciduum surrounding the implantation site, Overexpression of Hxt in mouse blastomeres directed their development into trophoblast cells in blastocysts, In addition, overexpression of Hxt induced the differentiation of rat trophoblast (Rcho-1) stem cells as assayed by changes in cell adhesion and by; activation of the placental lactogen-I gene promoter, a trophoblast giant cell-specific gene, In contrast, the negative HLH regulator, Id-1, inhibited Rcho-1 differentiation and placental lactogen-I transcription. These data demonstrate a role for HLH factors in regulating trophoblast development and indicate a positive role for Hxt in promoting the formation of trophoblast giant cells. C1 UNIV CALIF SAN FRANCISCO,DEPT ANAT,RADIOBIOL & ENVIRONM HLTH LAB,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEV BIOL PROGRAM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,HORMONE RES INST,SAN FRANCISCO,CA 94143. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Cross, James/F-4814-2011 OI Cross, James/0000-0003-0956-9378 FU NICHD NIH HHS [HD 23539, HD 26732]; NIDDK NIH HHS [DK-21344] NR 55 TC 258 Z9 262 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG PY 1995 VL 121 IS 8 BP 2513 EP 2523 PG 11 WC Developmental Biology SC Developmental Biology GA RN703 UT WOS:A1995RN70300024 PM 7671815 ER PT J AU TOYAMA, R CURTISS, PE OTANI, H KIMURA, M DAWID, IB TAIRA, M AF TOYAMA, R CURTISS, PE OTANI, H KIMURA, M DAWID, IB TAIRA, M TI THE LIM CLASS HOMEOBOX GENE LIM5 - IMPLIED ROLE IN CNS PATTERNING IN XENOPUS AND ZEBRAFISH SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MESODERM INDUCTION; BOX GENE; MIDBLASTULA TRANSITION; DNA-BINDING; EXPRESSION; LAEVIS; EMBRYOS; ACTIVIN; ORGANIZER AB LIM homeobox genes are characterized by encoding proteins in which two cysteine-rich LIM domains are associated with a homeodomain. We report the isolation of a gene, named Xlim-5 in Xenopus and lim5 in the zebrafish, that is highly similar in sequence but quite distinct in expression pattern from the previously described Xlim-1/lim1 gene. In both species studied the lim5 gene is expressed in the entire ectoderm in the early gastrula embryo. The Xlim-5 gene is activated in a cell autonomous manner in ectodermal cells, and this activation is suppressed by the mesoderm inducer activin. During neurulation, expression of the lim5 gene in both the frog and fish embryo is rapidly restricted to an anterior region in the developing neural plate/keel. In the 2-day Xenopus and 24-hr zebrafish embryo, this region becomes more sharply defined, forming a strongly lim5-expressing domain in the diencephalon anterior to the midbrain-forebrain boundary. In addition, regions of less intense lim5 expression are seen in the zebrafish embryo in parts of the telencephalon, in the anterior diencephalon co-incident with the postoptic commissure, and in restricted regions of the mid-brain, hindbrain, and spinal cord. Expression in ventral forebrain is abolished from the li-somite stage onward in cyclops mutant fish. These results imply a role for lim5 in the patterning of the nervous system, in particular in the early specification of the diencephalon. (C) 1995 Academic Press, Inc. RP TOYAMA, R (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 72 TC 59 Z9 62 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 583 EP 593 DI 10.1006/dbio.1995.1238 PG 11 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400027 PM 7649385 ER PT J AU ADLER, R BELECKYADAMS, T TOMAREV, S SUNDIN, O AF ADLER, R BELECKYADAMS, T TOMAREV, S SUNDIN, O TI CORRELATION BETWEEN PROX-1 AND PAX-6 HOMEOBOX GENE-EXPRESSION AND PHENOTYPIC FATE OF RETINAL PRECURSOR CELLS SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NEI,LMDB,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,DEPT OPHTHALMOL,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 740 EP 740 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400061 ER PT J AU STOLOW, MA SHI, YB AF STOLOW, MA SHI, YB TI XENOPUS SONIC HEDGEHOG AS A POTENTIAL MORPHOGEN DURING EMBRYOGENESIS AND THYROID HORMONE-DEPENDENT METAMORPHOSIS SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 752 EP 752 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400133 ER PT J AU SHI, YB STOLOW, M PUZIANOWSKAKUZNICKI, M AF SHI, YB STOLOW, M PUZIANOWSKAKUZNICKI, M TI THYROID HORMONE-DEPENDENT INTESTINAL MORPHOGENESIS - ROLES OF CELL-CELL AND CELL-ECM INTERACTIONS SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 753 EP 753 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400141 ER PT J AU PUZIANOWSKA, M KUZNICKI, Y SHI, B AF PUZIANOWSKA, M KUZNICKI, Y SHI, B TI DEVELOPMENTAL, SPATIAL AND FUNCTIONAL-ANALYSIS OF XENOPUS-LAEVIS NFI TRANSCRIPTION FACTORS SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 755 EP 755 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400154 ER PT J AU ERICKSON, W KOZAK, C KLEEMAN, J MACLEOD, C AF ERICKSON, W KOZAK, C KLEEMAN, J MACLEOD, C TI EXPRESSION OF ALTERNATELY SPLICED FORMS OF A LYMPHOID-SPECIFIC SAR/MAR BINDING-PROTEIN IN T-LYMPHOCYTES AND B-LYMPHOCYTES AND T-LYMPHOMA CELLS SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,BIOMED SCI GRAD PROGRAM,PROGRAM CANC GENET,LA JOLLA,CA 92093. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 757 EP 757 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400163 ER PT J AU STOLOW, DT HAYNES, S AF STOLOW, DT HAYNES, S TI TSR, A DROSOPHILA TESTIS-SPECIFIC RRM PROTEIN REQUIRED FOR SPERMATOGENESIS INTERACTS WITH ARF AND ARL SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 768 EP 768 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400229 ER PT J AU GAGNETEN, S BETHKE, BD SAUER, B AF GAGNETEN, S BETHKE, BD SAUER, B TI CRE RECOMBINASE LOCALIZES TO THE NUCLEUS OF MAMMALIAN-CELLS SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 769 EP 769 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400238 ER PT J AU HUANG, S SATO, S AF HUANG, S SATO, S TI ACTIVELY PROLIFERATING STEM-CELLS IN THE ADULT ZEBRAFISH BRAIN IDENTIFIED BY THE EXPRESSION OF A POU GENE, TAICHI SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 771 EP 771 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400248 ER PT J AU WITTA, SE SATO, SM AF WITTA, SE SATO, SM TI OVEREXPRESSION OF XIPOU-2 IN THE DORSAL MESODERM ALTERS EYE AND FIRST BRANCHIAL ARCH DEVELOPMENT SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1995 VL 170 IS 2 BP 772 EP 772 PG 1 WC Developmental Biology SC Developmental Biology GA RQ084 UT WOS:A1995RQ08400252 ER PT J AU LI, XA MA, W BARKER, JL PIATIGORSKY, J AF LI, XA MA, W BARKER, JL PIATIGORSKY, J TI TRANSIENT EXPRESSION OF GLUTAMATE-DECARBOXYLASE AND GAMMA-AMINO BUTYRIC-ACID IN EMBRYONIC LENS FIBERS OF THE RAT SO DEVELOPMENTAL DYNAMICS LA English DT Article DE LENS; IMMUNOCYTOCHEMISTRY; LENS DEVELOPMENT; TRANSIENT EXPRESSION; GLUTAMATE DECARBOXYLASE (GAD); PCR; RAT ID AMINOBUTYRIC-ACID; SPINAL-CORD; GENE; CELLS; MOUSE; IMMUNOREACTIVITY; LOCALIZATION; FORMS; BRAIN; GABA AB We have determined the localization and developmental expression of glutamate decarboxylase (GAD67) in the rat lens. Immunofluorescence experiments showed that GAD67 was transiently expressed in the nuclear fiber cells of the lens between embryonic days (E) 15 and 20, with maximal immunostaining occurring on E17 and E18. gamma-amino butyric acid (GABA) co-localized with GAD67 in the embryonic nuclear fiber cells, Reverse transcription-polymerase chain reaction (RT-PCR) tests showed that at least three alternatively spliced forms of GAD67 mRNA, including mRNAs with and without the I80 and the I86 insert, were transiently co-expressed with GAD67 in the embryonic lens. The major GAD67 protein in the lens was 67 kDa. We conclude that enzymatically active GAD67 is transiently expressed in the lens nuclear fiber cells of the embryonic rat. The transient expression is regulated by transcriptional and/or posttranscriptional processes. We speculate on the basis of possible common gene regulatory elements for glutamate and ornithine decarboxylases and the involvement of these enzymes with polyamine synthesis, that the transient expression of GAD67 may be connected to nuclear and/or DNA breakdown during lens fiber cell differentiation. (C) 1995 Wiley-Liss, Inc.* C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 38 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 1995 VL 203 IS 4 BP 448 EP 455 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA RN559 UT WOS:A1995RN55900006 PM 7496036 ER PT J AU BORDIN, S CARNEIRO, EM ATWATER, I ROJAS, E BOSCHERO, AC AF BORDIN, S CARNEIRO, EM ATWATER, I ROJAS, E BOSCHERO, AC TI MODULATION OF CA2+ AND K2+ PERMEABILITIES BY OXOTREMORINE-M (OXO-M) IN PANCREATIC B-CELLS SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV ESTADUAL CAMPINAS,BR-13100 CAMPINAS,SP,BRAZIL. NIDDK,BETHESDA,MD. RI Carneiro, Everardo /D-4758-2012; Boschero, Antonio/O-7525-2014 OI Boschero, Antonio/0000-0003-3829-8570 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A118 EP A118 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400455 ER PT J AU NAGI, DK TRACY, RP PRATLEY, R AF NAGI, DK TRACY, RP PRATLEY, R TI EFFECTS OF ENDOGENOUS AND EXOGENOUS HYPERINSULINEMIA ON PLASMINOGEN-ACTIVATOR INHIBITOR (PAI-1) IN PIMA-INDIANS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ. VERMONT TROMBOSIS CTR,BURLINGTON,VT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A139 EP A139 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400535 ER PT J AU NELSON, RG SIEVERS, ML BENNETT, PH AF NELSON, RG SIEVERS, ML BENNETT, PH TI DECLINING DEATH RATE FROM NEPHROPATHY IN PIMA-INDIANS WITH NON-INSULIN-DEPENDENT DIABETES SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A63 EP A63 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400244 ER PT J AU PERFETTI, R MONTROSERAFIZADEH, C EGAN, JM AF PERFETTI, R MONTROSERAFIZADEH, C EGAN, JM TI AGE-RELATED-CHANGES IN RAT ISLET BETA-CELLS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A94 EP A94 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400363 ER PT J AU PETTITT, D ROUMAIN, J HANSON, R KNOWLER, W BENNETT, P AF PETTITT, D ROUMAIN, J HANSON, R KNOWLER, W BENNETT, P TI LOWER GLUCOSE IN PREGNANT AND NONPREGNANT PIMA-INDIANS WHO WERE BREAST-FED AS INFANTS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A61 EP A61 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400233 ER PT J AU ROUDINOUE, C LONDOS, C SMITH, U AF ROUDINOUE, C LONDOS, C SMITH, U TI OKADAIC ACID PREVENTS THE INHIBITORY EFFECT OF STAUROSPORINE ON INSULIN ACTION IN RAT ADIPOCYTES SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. GOTHENBURG UNIV,SAHLGRENS HOSP,DEPT INTERNAL MED,LUNBERG LAB DIABET RES,S-41345 GOTHENBURG,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1995 VL 38 SU 1 BP A122 EP A122 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ184 UT WOS:A1995RQ18400471 ER PT J AU COMBADIERE, C AHUJA, SK MURPHY, PM AF COMBADIERE, C AHUJA, SK MURPHY, PM TI CLONING, CHROMOSOMAL LOCALIZATION, AND RNA EXPRESSION OF A HUMAN BETA CHEMOKINE RECEPTOR-LIKE GENE SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; FAMILY AB A human cDNA encoding a putative G protein-coupled receptor designated chemokine beta receptor-like 1 (CMKBRL1) was isolated from an eosinophilic leukemia library. Its deduced sequence is similar to 40% identical to previously cloned receptors for the beta chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), which are chemoattractants for blood leukocytes, and is 83% identical to the product of the orphan rat cDNA RES 11, Like the MIP-1 alpha/RANTES receptor, CMKBRL1 is encoded by a small, single-copy gene that maps to chromosome 3p21 and is expressed in leukocytes, However, two screening assays with a broad panel of chemokines failed to identify its ligand, CMKBRL1 mRNA was detectable by Northern blot hybridization in neutrophils and monocytes, hut not eosinophils, and was also found in eight solid organs that were tested with particularly high expression in brain, The RNA distribution of the known beta chemokine receptors was overlapping but distinct from that of CMKBRL1. MIP-1 alpha/RANTES receptor mRNA was detectable in neutrophils, monocytes, eosinophils, and in all eight solid organs tested, with particularly high expression in placenta, lung, and Ever, MCP-1 receptor mRNA was found in monocytes, lung, liver, and pancreas, These results suggest that the ligand for the putative CMKBRRL1 receptor is a beta chemokine that targets both neutrophils and monocytes, Moreover, the RNA distributions suggest that CMKBRL1, the MIP-1 alpha/RANTES receptor, and the MCP-1 receptor may have both overlapping and distinct biological roles. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 20 TC 74 Z9 76 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 1995 VL 14 IS 8 BP 673 EP 680 DI 10.1089/dna.1995.14.673 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA RR470 UT WOS:A1995RR47000003 PM 7646814 ER PT J AU CHEN, HW LIN, BC CHEN, CL JOHNSON, PF CHOU, JY AF CHEN, HW LIN, BC CHEN, CL JOHNSON, PF CHOU, JY TI ROLE OF THE TRANSCRIPTION FACTOR C/EBP-BETA IN EXPRESSION OF A RAT PREGNANCY-SPECIFIC GLYCOPROTEIN GENE SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; ENHANCER BINDING-PROTEIN; ALPHA-SUBUNIT GENE; CARCINOEMBRYONIC ANTIGEN; HUMAN TROPHOBLASTS; INTERLEUKIN-6 IL-6; HUMAN PROLACTIN; NUCLEAR FACTOR; HORMONE GENE; C-FMS AB Pregnancy-specific glycoproteins (PSGs), which are the major placental proteins, and the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily, To understand the molecular mechanisms underlying the control of PSG expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3, and showed that DNA elements at nucleotides -326 to -185 (PI) relative to the translation start site of rnCGM3 function as a promoter. The rnCGM3 PI promoter contains two placental factor binding sites, PISI and PISII, Both are transcription activation elements, In the present report, we screened a placental expression cDNA library with a rnCGM3-PISII probe (nucleotides -263 to -233) encompassing two overlapping palindromes (TGTTGCTCAACATGTTG) and demonstrated that the PISII-binding factor is C/EBP beta, a leucine zipper family of transcription factor, Gel mobility-shift and transient expression analyses showed that C/EBP beta and C/EBP isoforms, C/EBP alpha and C/EBP delta, bind to the PISII element and trans-activate rnCGM3 gene expression, Deletion of PISII from the rnCGM3 PI promoter greatly reduced the basal as well as the C/EBP-activated rnCGM3 expression, Gel supershift assays demonstrated that C/EBP beta is the placental isoform that binds to the PISII site rnCGM3. Moreover, C/EBP beta is expressed ion high levels in the placenta, ovary, liver, lung, heart, and spleen, in contrast to C/EBP alpha, which is expressed primarily in the liver and only low levels in the placenta. Our results demonstrate that C/EBP beta is one of the transcription factors that positively regulate rnCGM3 expression during pregnancy. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV FLORIDA,DEPT LARGE ANIM CLIN SCI,GAINESVILLE,FL 32610. FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21712. RI Johnson, Peter/A-1940-2012; Lin, Baochuan/A-8390-2009 OI Johnson, Peter/0000-0002-4145-4725; Lin, Baochuan/0000-0002-9484-0785 NR 52 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 1995 VL 14 IS 8 BP 681 EP 688 DI 10.1089/dna.1995.14.681 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA RR470 UT WOS:A1995RR47000004 PM 7646815 ER PT J AU BOISCLAIR, YR BROWN, AL AF BOISCLAIR, YR BROWN, AL TI USE OF REVERSE LIGATION-PCR TO IDENTIFY TRANSCRIPTIONAL START SITES IN GC-RICH TATA-LESS GENES - APPLICATION TO THE RAT IGFBP-2 GENE SO DNA AND CELL BIOLOGY LA English DT Article ID FACTOR-BINDING PROTEIN-2; RNA POLYMERASE-II; GROWTH FACTOR-I; RECEPTOR PROMOTER; MESSENGER-RNAS; EXPRESSION; CLONING; SP1; IDENTIFICATION; INITIATION AB TATA-less genes are often GC-rich in the region of transcriptional initiation and the corresponding mRNAs are prone to the formation of secondary structure, These properties have made it difficult to determine unambiguously the start sites of transcription for some of these genes by conventional assays such as primer extension and nuclease protection, Using the TATA-less rat IGFBP-2 gene, we demonstrate that tobacco acid pyrophosphatase-reverse ligation polymerase chain reaction (TAP-RLPCR), a novel and sensitive assay, can be used to map the start sites of these genes, First, the validity of TAP-RLPCR was demonstrated by mapping the transcription start site of the rat insulin-Bike growth factor 1 (IGFBP-1) gene to the correct position (nucleotides -173 relative to ATG, +1). Using total RNA obtained from the rat liver cell line BRL-3A, the transcription start sites of the rat IGFBP-2 gene were mapped to a narrow cluster extending from nucleotides -86 to -90 (ATG, +1), 39 bp downstream of three adjacent GC boxes that are essential to the transcriptional activity of the gene, The assay was also used to map the start sites of a luciferase reporter gene driven by the fragment -1,295 to -32 of the rat IGFBP-2 promoter after transfection in the human embryonic kidney cell line 293, The hybrid gene utilized the same transcription start sites as the rat IGFBP-2 gene, indicating that the elements required for positioning of the transcription initiation complex are contained within the 3' end terminating at nucleotide -32, These studies demonstrate the usefulness of the TAP-RLPCR assay for verifying the authenticity of ambiguous start sites, and definitively map the start sites of the rat IGFBP-2 gene. RP BOISCLAIR, YR (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,ROOM 8D14,BETHESDA,MD 20892, USA. NR 33 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 1995 VL 14 IS 8 BP 731 EP 739 DI 10.1089/dna.1995.14.731 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA RR470 UT WOS:A1995RR47000009 PM 7544133 ER PT J AU PICKENS, RW SVIKIS, DS MCGUE, M LABUDA, MC AF PICKENS, RW SVIKIS, DS MCGUE, M LABUDA, MC TI COMMON GENETIC MECHANISMS IN ALCOHOL, DRUG, AND MENTAL DISORDER COMORBIDITY SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE GENETICS; COMORBIDITY; TWINS; ALCOHOLISM; DRUG ABUSE; MENTAL DISORDERS ID PSYCHIATRIC-DISORDERS; FAMILIAL TRANSMISSION; PANIC DISORDER; MAJOR DEPRESSION; ABUSE; RELATIVES; PROBANDS; TWIN; PSYCHOPATHOLOGY; INHERITANCE AB Comorbid drug and mental disorders were assessed in 63 monozygotic (MZ) and 67 dizygotic (DZ) twin pairs. DSM-III alcohol dependence was heritable in males when probands had a comorbid DSM-III drug or mental disorder but not when probands had only alcohol dependence. For males, significantly higher cross-MZ than cross-DZ correlations were found between alcohol dependence in probands and certain mental and drug disorders in cotwins. In contrast, females showed higher within-twin than cross-MZ correlations and similar cross-MZ and cross-DZ correlations between alcohol dependence and all mental and drug disorders. These results suggest comorbidity between alcohol and certain drug and mental disorders in males in epidemiological surveys may be due in part to genetic influences. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. UNIV MINNESOTA,DEPT PSYCHOL,MINNEAPOLIS,MN 55455. RP PICKENS, RW (reprint author), NIDA,DIV INTRAMURAL RES,POB 5180,BALTIMORE,MD 21224, USA. FU NIAAA NIH HHS [AA 06500, AA00175] NR 68 TC 70 Z9 71 U1 3 U2 5 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG PY 1995 VL 39 IS 2 BP 129 EP 138 DI 10.1016/0376-8716(95)01151-N PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA RU986 UT WOS:A1995RU98600006 PM 8529532 ER PT J AU CHESKIN, LJ CHAMI, TN JOHNSON, RE JAFFE, JH AF CHESKIN, LJ CHAMI, TN JOHNSON, RE JAFFE, JH TI ASSESSMENT OF NALMEFENE GLUCURONIDE AS A SELECTIVE GUT OPIOID ANTAGONIST SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE OPIOID ANTAGONISTS; CONSTIPATION; OPIOIDS; NALMEFENE ID ORAL NALOXONE; CONSTIPATION; TRANSIT AB Opioid use often causes troublesome constipation as a side-effect. Selective antagonism of the intestinal actions of opioids might be useful in the treatment of opioid-induced constipation. We tested the inactive metabolite of nalmefene, nalmefene glucuronide, which showed promise of gut selectivity in rodent models, by administering ascending doses in single-blind, placebo-controlled fashion to five methadone-maintained, opioid-dependent male volunteers. Assessment of whether systemic or gut-selective opioid antagonist effects occurred was measured by vital signs, pupillary diameter, opioid withdrawal symptom scales, and bowel function. Oral nalmefene glucuronide precipitated symptoms and signs consistent with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after dosing. We conclude that nalmefene glucuronide does not appear to exert sufficient gut selectivity to be useful in antagonizing constipation due to exogenous opioid administration without antagonizing systemic opioid effects. C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. RP CHESKIN, LJ (reprint author), JOHNS HOPKINS UNIV,SCH MED,BAYVIEW MED CTR,DIV GASTROENTEROL,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG PY 1995 VL 39 IS 2 BP 151 EP 154 DI 10.1016/0376-8716(95)01153-P PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA RU986 UT WOS:A1995RU98600008 PM 8529534 ER PT J AU WEISS, GH GARNER, M YARMOLA, E BOCEK, P CHRAMBACH, A AF WEISS, GH GARNER, M YARMOLA, E BOCEK, P CHRAMBACH, A TI A COMPARISON OF RESOLUTION OF DNA FRAGMENTS BETWEEN AGAROSE-GEL AND CAPILLARY ZONE ELECTROPHORESIS IN AGAROSE SOLUTIONS SO ELECTROPHORESIS LA English DT Article DE RESOLUTION; DNA; CAPILLARY ZONE ELECTROPHORESIS; GEL ELECTROPHORESIS ID POLYACRYLAMIDE AB The resolving power of capillary zone electrophoresis (CZE) is compared to that of gel electrophoresis (GE) under similar conditions (agarose, similar length of DNA fragments, identical buffer) but with differences in temperature and field strength. The comparison is based on the time required to reach a desired degree of resolution by each of the two methods. A resolution parameter is developed which is equally applicable to CZE, with relatively diffuse initial conditions in the absence of stacking and measurements expressed in terms of time, and to GE, in which measurements are expressed in terms of spatial parameters. The resolution time in CZE using agarose solutions at 40 degrees C was found to be greater by at least one order of magnitude than that in GE using agarose gels. Thus, the increased migration velocity due to high field strength in CZE substantially outweighs the lower dispersion in GE. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NATL INST HLTH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD. RUSSIAN ACAD SCI,INST MOLEC BIOL,MOSCOW,RUSSIA. ACAD SCI CZECH REPUBL,INST ANALYT CHEM,CS-61142 BRNO,CZECH REPUBLIC. RI Bocek, Petr/G-6821-2014 NR 15 TC 14 Z9 14 U1 2 U2 7 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 AUG PY 1995 VL 16 IS 8 BP 1345 EP 1353 DI 10.1002/elps.11501601222 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RV111 UT WOS:A1995RV11100006 PM 8529595 ER PT J AU URA, K HAYES, JJ WOLFFE, AP AF URA, K HAYES, JJ WOLFFE, AP TI A POSITIVE ROLE FOR NUCLEOSOME MOBILITY IN THE TRANSCRIPTIONAL ACTIVITY OF CHROMATIN TEMPLATES - RESTRICTION BY LINKER HISTONES SO EMBO JOURNAL LA English DT Article DE HISTONES; LINKER; NUCLEOSOMAL TEMPLATES; REPRESSION; TRANSCRIPTION ID RNA POLYMERASE-II; HIGHER-ORDER STRUCTURE; DNA-REPLICATION; CORE PARTICLE; GENES; SEQUENCE; COMPLEX; INVITRO; ACETYLATION; TRANSCRIBES AB Nucleosome mobility facilitates the transcription of chromatin templates containing only histone octamers. Inclusion of linker histones in chromatin inhibits nucleosome mobility, directs nucleosome positioning and represses transcription. Transcriptional repression by linker histone occurs preferentially on templates associated with histone octamers relative to naked DNA. Mobile nucleosomes and the restriction of mobility by linker histones might be expected to exert a major influence on the accessibility of chromatin to regulatory molecules. RP URA, K (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,RM B1A-13,BETHESDA,MD 20892, USA. NR 80 TC 159 Z9 159 U1 0 U2 2 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 AUG 1 PY 1995 VL 14 IS 15 BP 3752 EP 3765 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RN943 UT WOS:A1995RN94300017 PM 7641694 ER PT J AU KOHN, LD AF KOHN, LD TI THYROGLOBULIN - A NEW CYCLIC ADENOSINE MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE SO ENDOCRINOLOGY LA English DT Editorial Material ID GROWTH FACTOR-I; EXPRESSION; PROMOTER; INSULIN; TISSUE; CELLS; BINDS RP KOHN, LD (reprint author), NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3177 EP 3178 DI 10.1210/en.136.8.3177 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200001 PM 7628348 ER PT J AU MAKINO, S SMITH, MA GOLD, PW AF MAKINO, S SMITH, MA GOLD, PW TI INCREASED EXPRESSION OF CORTICOTROPIN-RELEASING HORMONE AND VASOPRESSIN MESSENGER-RIBONUCLEIC-ACID (MESSENGER-RNA) IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS DURING REPEATED STRESS - ASSOCIATION WITH REDUCTION IN GLUCOCORTICOID RECEPTOR MESSENGER-RNA LEVELS SO ENDOCRINOLOGY LA English DT Article ID REPEATED IMMOBILIZATION STRESS; PITUITARY-ADRENOCORTICAL AXIS; RAT-BRAIN; MINERALOCORTICOID RECEPTOR; TYROSINE-HYDROXYLASE; RNA EXPRESSION; BIOCHEMICAL MANIFESTATIONS; THERAPEUTIC IMPLICATIONS; GENE-EXPRESSION; ADRENAL AXIS AB Hypothalamic-pituitary-adrenal (HPA) responses remain intact or increase after chronic or repeated stress despite robust levels of circulating glucocorticoids that would be expected to restrain the responsiveness of the axis. The purpose of this study was to determine whether chronic stress altered corticosteroid receptor messenger RNA (mRNA) levels at any locus known to mediate glucocorticoid feedback on HPA function (i.e. hippocampus or hypothalamus), whether such effects were glucocorticoid dependent, and whether changes in corticosteroid receptor function could potentially contribute to the putative shift from corticotropin-releasing hormone (CRH) to arginine vasopressin (AVP) in the hypothalamic paraventricular nucleus (PVN) in the modulation of pituitary adrenal function occur ring during chronic stress. We compared the stress responsiveness of sham-operated rats to that of adrenalectomized rats using a moderate dose of corticosterone (CORT) pellet replacement (ADX + CORT group). Acute immobilization caused a significant increase in CRH, but not AVP, mRNA levels in the parvocellular PVN in sham rats. The ADX + CORT group showed significantly greater increases in both CRH and AVP mRNA levels in the PVN compared to sham rats. These data indicate that PVN AVP mRNA levels are more sensitive to glucocorticoid negative feedback than are the levels of CRH mRNA. In repeated stress, the sham groups showed robust increases in PVN CRH and AVP mRNA levels despite high levels of plasma CORT. The rise in AVP mRNA levels was greater than that in CRH mRNA. Type II glucocorticoid receptor mRNA in the hippocampus and PVN was decreased in the repeatedly stressed sham group. These data suggest a decrease in the CORT negative feedback restraint of PVN CRH and AVP mRNA levels after repeated stress and a persistence of relatively greater responsiveness of AVP mRNA levels to CORT negative feedback. After repeated stress in ADX + CORT rats, both PVN CRH and AVP mRNA levels showed robust responses, with a relatively greater increase in AVP mRNA. These data indicate that a CORT-mediated decrease in hippocampal and hypothalamic glucocorticoid receptor mRNA levels is not the only mechanism contributing to the maintenance of a robust HPA response after repeated stress. Similarly, we postulate that the relative shift from CRH to AVP in the PVN after repeated stress is mediated by both a greater sensitivity of AVP to CORT negative feedback and CORT-independent mechanisms. C1 NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. RP NIMH, CLIN NEUROENDOCRINOL BRANCH, BLDG 10, ROOM 3S-231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 53 TC 274 Z9 277 U1 1 U2 9 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3299 EP 3309 DI 10.1210/en.136.8.3299 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200018 PM 7628364 ER PT J AU SZKUDLINSKI, MW THOTAKURA, NR TROPEA, JE GROSSMANN, M WEINTRAUB, BD AF SZKUDLINSKI, MW THOTAKURA, NR TROPEA, JE GROSSMANN, M WEINTRAUB, BD TI ASPARAGINE-LINKED OLIGOSACCHARIDE STRUCTURES DETERMINE CLEARANCE AND ORGAN DISTRIBUTION OF PITUITARY AND RECOMBINANT THYROTROPIN SO ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; GLYCOPROTEIN HORMONES; BIOACTIVITY; RECEPTORS; LIVER; TSH; RAT AB The recombinant human TSH (rhTSH) with highly sialylated oligosaccharide chains showed higher in vivo bioactivity and a lower MCR than the predominantly sulfated pituitary human TSH (phTSH). The aim of the present study was to investigate the role of terminal carbohydrate residues in organ distribution and metabolic clearance of TSH using an in vivo rat model. The different I-125-labeled TSH preparations with distinct carbohydrate composition were injected iv. At various time points (5-180 min) after bolus TSH injection, blood, liver, kidney, spleen, lung, heart, and thyroid samples were collected. TSH uptake was determined by trichloroacetic acid precipitation of [I-125]TSH in the organ homogenates. The rhTSH (solely sialylated) was distributed predominantly to the kidneys 5, 15, and 30 min after injection. In contrast, phTSH (sulfated/sialylated) and bovine TSH (bTSH; solely sulfated) were cleared predominantly by the liver (at 5 min), with a later renal phase of clearance (at 30 min). Asialo-rhTSH was cleared by the liver with only minor involvement of other organs. The early liver uptake (at 5 min) was proportionally highest for the asialo-rhTSH and bTSH preparations and lowest for rhTSH, which correlated inversely with the serum levels and the degree of sialylation. Blockade of the N-acetylgalactosamine (GalNAc) sulfate receptors by injection of bovine LH resulted in a significant decrease in liver uptake of phTSH. Similarly, liver uptake of asialo-rhTSH was significantly inhibited by injection of asialo-fetuin. Thus, phTSH and bTSH preparations containing sulfated oligosaccharide chains are cleared at least in part by the GalNAc sulfate-specific receptors in the liver. In contrast, rhTSH with highly sialylated oligosaccharides in both subunits accumulates predominantly in the kidneys, even at the early phase of clearance, indicating that sialylated glycoprotein hormones escape from specific receptor-mediated clearance mechanisms in the liver. These data indicate that terminal sialic acid and GalNAc sulfate residues, each to a different extent, determine glycoprotein hormone distribution and thereby plasma level, which as we have shown previously is a major factor in determining the in vivo potency of TSH. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 26 TC 59 Z9 60 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3325 EP 3330 DI 10.1210/en.136.8.3325 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200021 PM 7628367 ER PT J AU JOBIN, RM TOMIC, M ZHENG, LX STOJILKOVIC, SS CATT, KJ AF JOBIN, RM TOMIC, M ZHENG, LX STOJILKOVIC, SS CATT, KJ TI GONADOTROPIN-RELEASING HORMONE-INDUCED SENSITIZATION OF CALCIUM-DEPENDENT EXOCYTOSIS IN PITUITARY GONADOTROPHS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; PHORBOL ESTER; SECRETORY RESPONSES; CYTOSOLIC PROTEIN; CHROMAFFIN CELLS; HUMAN-PLATELETS; GH4C1 CELLS; INHIBITION; MECHANISM; OSCILLATIONS AB Agonist-induced increases in cytoplasmic calcium concentration ([Ca2+](i)) play a pivotal role in regulated exocytosis by promoting the fusion of secretory vesicles with the plasma membrane. In permeabilized and ATP-primed pituitary cells, increases in ambient [Ca2+](i) stimulated the release of LH from gonadotrophs with an EC(50) of 2-3 mu M. In contrast, the responses of intact gonadotrophs to agonist stimulation by GnRH were characterized by transient [Ca2+](i) elevations of up to 1.5 mu M, followed by a plateau of 300-400 nM. The sensitivity of the exocytotic response of permeabilized cells to [Ca2+](i) was significantly increased by GnRH, which reduced the EC(50) for [Ca2+](i) to the submicromolar concentration range. The stimulatory action of GnRH on LH release in permeabilized cells was not a consequence of intracellular Ca2+ release, but was associated with increased cytidine diphosphate diacylglycerol production Activation of protein kinase C by phorbol esters caused a similar increase in the Ca2+ sensitivity of LH release from permeabilized cells, and this effect was not additive to that of GnRH. Furthermore, the GnRH-induced increase in the sensitivity of the exocytotic response to Ca2+ was attenuated by inhibitors of protein kinase C. These findings indicate that although elevated [Ca2+](i) per se can promote LH release from permeabilized gonadotrophs, concomitant activation of protein kinase C is necessary to support exocytosis at the physiological [Ca2+](i) levels that prevail in GnRH-stimulated intact cells. Such sensitization of the Ca2+-dependent secretory mechanism by protein kinase C may be an important step in the agonist-induced release of LH from pituitary gonadotrophs. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. RI Tomic, Melanija/C-3371-2016 NR 58 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 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3398 EP 3405 DI 10.1210/en.136.8.3398 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200030 PM 7628375 ER PT J AU TOMIC, M DUFAU, ML CATT, KJ STOJILKOVIC, SS AF TOMIC, M DUFAU, ML CATT, KJ STOJILKOVIC, SS TI CALCIUM SIGNALING IN SINGLE-RAT LEYDIG-CELLS SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; PROTEIN KINASE-C; LUTEINIZING-HORMONE; ADENOSINE-MONOPHOSPHATE; PITUITARY GONADOTROPHS; GRANULOSA-CELLS; CA2+ MOBILIZATION; GNRH RECEPTORS; ACTIVATION; EXPRESSION AB The steroidogenic activity of the Leydig cell is regulated by glycoprotein and peptide hormones with the potential to activate both adenylate cyclase and phospholipase C. Although the control of androgen production by LH is clearly mediated by cAMP, the extent to which Ca2+-mobilizing stimuli control Leydig cell function is less well defined. The basal level of intracellular calcium ([Ca2+](i)) in adult rat Leydig cells was 70-160 nM and was unaffected by high K+ or the dihydropyridine calcium channel agonist, Bay K 8644. These findings are consistent with the absence of voltage-sensitive calcium channels in the Leydig cell. In addition, no increase in [Ca2+]i was observed in cells treated with LH, CRF, and serotonin. However, both GnRH and endothelin-1 (ET-1) induced rapid and transient elevations of [Ca2+](i) that were not associated with a sustained plateau phase and were unaffected by removal of Ca2+ from the incubation medium. The amplitude of the [Ca2+](i) response was not altered by increasing concentrations of GnRH and ET-1, but the number of responsive cells increased progressively to a maximum of about 30% of the Leydig cell population. The calcium-mobilizing actions of GnRH and ET-1 were abolished by the GnRH and ET(A) receptor antagonists, [Dp-Glu(1),D-Phe(2),D-Trp(3,6)]GnRH and BQ-123, respectively. The majority of the cells expressed solely GnRH or ET(A) receptors, and about 10% expressed both receptors. GnRH-induced Ca2+ responses were observed almost exclusively in medium-sized Leydig cells, whereas ET-induced responses were most frequent in large Leydig cells. These data demonstrate that single Leydig cells expressing GnRH and ET(A) receptors exhibit monophasic [Ca2+](i) responses that are activated in an all-or-none fashion. Such transient Ca2+ signaling may trigger short term cellular responses or could modulate the actions of gonadotropins acting through the cAMP signaling pathway. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. RI Tomic, Melanija/C-3371-2016 NR 52 TC 31 Z9 31 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3422 EP 3429 DI 10.1210/en.136.8.3422 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200033 PM 7628378 ER PT J AU KABURAGI, Y YAMAMOTOHONDA, R TOBE, K UEKI, K YACHI, M AKANUMA, Y STEPHENS, RM KAPLAN, D YAZAKI, Y KADOWAKI, T AF KABURAGI, Y YAMAMOTOHONDA, R TOBE, K UEKI, K YACHI, M AKANUMA, Y STEPHENS, RM KAPLAN, D YAZAKI, Y KADOWAKI, T TI THE ROLE OF THE NPXY MOTIF IN THE INSULIN-RECEPTOR IN TYROSINE PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 AND SHC SO ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-I; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; PROTEIN; GRB2; RAS; DOMAIN; NUCLEOTIDE; HOMOLOGY; REGION AB The insulin receptor phosphorylates insulin receptor substrate-1 (IRS-1) and Shc on tyrosine residues, both of which associate with the protein-abundant Src homology/growth factor receptor-bound protein 2 (ASH/GRB2) leading to p21(ras) activation. Juxtamembrane Tyr(960) of the insulin receptor required for tyrosine phosphorylation of both IRS-1 and Shc is contained in the NPXY motif, which is also present in other tyrosine kinase receptors and oncogene products. In this study, the role of this motif in insulin's signaling was examined in Chinese hamster ovary cells expressing insulin receptors with mutations in this motif. All alterations in Tyr(960) examined decreased tyrosine phosphorylation of both IRS-1 and Shc to a similar extent. The replacements of Asn(957) and the deletion of NPE impaired tyrosine phosphorylation of Shc and IRS-1, although tyrosine phosphorylation of Shc was more severely affected than that of IRS-1. The amount of ASH/GRB2 bound to IRS-1 and Shc in vitro and in vivo was also decreased in these cells. These data suggest that the NPXY motif in the insulin receptor is important for tyrosine phosphorylation of both IRS-1 and Shc as well as subsequent signaling. C1 ASAHI LIFE FDN,INST DIABET CARE & RES,CHIYODA KU,TOKYO 100,JAPAN. SANKYO CO LTD,PHARMACOL & MOLEC BIOL RES LABS,SHINAGAWA KU,TOKYO 140,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702. RP KABURAGI, Y (reprint author), UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,7-3-1 HONGO,TOKYO 113,JAPAN. NR 50 TC 37 Z9 38 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1995 VL 136 IS 8 BP 3437 EP 3443 DI 10.1210/en.136.8.3437 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200035 PM 7543044 ER PT J AU ERWIN, RA KIRKEN, RA MALABARBA, MG FARRAR, WL RUI, H AF ERWIN, RA KIRKEN, RA MALABARBA, MG FARRAR, WL RUI, H TI PROLACTIN ACTIVATES RAS VIA SIGNALING PROTEINS SHC, GROWTH-FACTOR RECEPTOR-BOUND-2, AND SON-OF-SEVENLESS SO ENDOCRINOLOGY LA English DT Article ID TYROSINE KINASE; HORMONE; MOUSE AB Identification of the signal transduction pathways used by PRL is essential for understanding the role of PRL receptors in growth and differentiation processes. Early cellular mediators of PRL receptor activation include tyrosine kinases of the Janus kinase (JAK) and SRC families, with rapid nuclear signaling via tyrosine phosphorylated signal transducers and activators of transcription. In the present study we provide the first demonstration of PRL-induced activation of Ras, an oncogenic protein that supports an alternative signaling route from the membrane to the nucleus. PRL stimulated Ras in rat Nb2-SP lymphoma cells, as detected by a 2.0-fold increase in the GTP-bound state of the molecule (P < 0.01). This activation was associated with marked tyrosine phosphorylation and increased membrane association of the 52-kilodalton form of SHC. Moreover, PRL induced binding of SHC to growth factor receptor bound 2 and the guanine-nucleotide exchange factor son of sevenless, a common method used by growth factor receptors to activate Ras. In contrast, no apparent regulation by PRL of Ras via VAV or p120 Ras-guanosine triphosphatase-activating protein was detected, based upon an absence of PRL-inducible tyrosine phosphorylation of these proteins. Collectively, these results provide a molecular bridge between activation of PRL receptor-associated tyrosine kinases and subsequent stimulation of the serine/threonine kinase Raf-1, an established Ras target that was recently shown to be activated by PRL in Nb2 cells. We conclude that PRL is able to activate Ras via recruitment of the signaling proteins SHC, growth factor receptor bound 2, and son of sevenless in Nb2 cells. Moreover, PRL induced tyrosine phosphorylation of SHC in two of three PRL-responsive human breast cancer cell lines, suggesting that SHC-mediated Ras activation is a commonly used signaling strategy by PRL. C1 NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. RI Malabarba, Maria Grazia/L-4805-2015 OI Malabarba, Maria Grazia/0000-0002-9457-2047 NR 41 TC 102 Z9 102 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 AUG PY 1995 VL 136 IS 8 BP 3512 EP 3518 DI 10.1210/en.136.8.3512 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RL632 UT WOS:A1995RL63200044 PM 7628388 ER PT J AU Hayes, HM Tarone, RE Cantor, KP AF Hayes, HM Tarone, RE Cantor, KP TI On the association between canine malignant lymphoma and opportunity for exposure to 2,4-dichlorophenoxyacetic acid SO ENVIRONMENTAL RESEARCH LA English DT Article AB In response to criticisms raised regarding a case-control study of canine malignant lymphoma, the results of several ancillary analyses are reported. The case-control study demonstrated a significant association between risk for canine malignant lymphoma and the opportunity for exposure to 2,4-dichlorophenoxyacetic acid herbicides. It is demonstrated that risk estimates do not vary by type of control group (i.e., tumor control or nontumor control group), by method of response (i.e., self-administered or telephone interview), or by geographic area. Questions related to the potential for referral bias, supposed inconsistencies in subject responses regarding frequency of herbicide use, and ambiguities regarding exposure classification are also examined. (C) 1995 Academic Press, Inc. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. RP Hayes, HM (reprint author), NCI,EPN,ENVIRONM EPIDEMIOL BRANCH,ROOM 443,BETHESDA,MD 20892, USA. NR 12 TC 30 Z9 30 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD AUG PY 1995 VL 70 IS 2 BP 119 EP 125 DI 10.1006/enrs.1995.1056 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA UW191 UT WOS:A1995UW19100006 PM 8674480 ER PT J AU MENDZ, GL BARDEN, JA MARTENSON, RE AF MENDZ, GL BARDEN, JA MARTENSON, RE TI CONFORMATION OF A TETRADECAPEPTIDE EPITOPE OF MYELIN BASIC-PROTEIN SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA Russian DT Article DE CONFORMATION; EPITOPE; MYELIN BASIC PROTEIN; NMR ID MONOCLONAL-ANTIBODIES; ALLERGIC ENCEPHALOMYELITIS; ANTIGENIC DETERMINANT; NMR-SPECTRA; PEPTIDE; MACROMOLECULES; RESIDUES; RABBIT; MONKEY; C-13 AB The peptide AcAla-Ser-Gln-Lys-Arg-Pro-Ser-Gln-Arg-His-Gly-Ser-Lys-Tyr, which comprises the first 14 residues of the acetylated N-terminus of myelin basic protein, is an epitopic site for two monoclonal antibodies to the human protein. The conformations of the tetradecapeptide in aqueous solutions were investigated employing high-resolution H-1- and C-13-NMR spectroscopy. Two-dimensional techniques were used to assign the spectra observed from both nuclei. Nuclear-Overhauser-effect data, amide proton temperature coefficients,C-13 spin-lattice relaxation times, distance geometry calculations and dynamic simulated annealing provided evidence that the solution conformations of the tetradecapeptide included a nascent a-helix in the N-terminal segment, and a loop extending from Ser7 to Ser12 that bring His10 and Tyr14 into close proximity. C1 UNIV SYDNEY,DEPT ANAT & HISTOL,SYDNEY,NSW 2006,AUSTRALIA. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP MENDZ, GL (reprint author), UNIV NEW S WALES,SCH BIOCHEM & MOLEC GENET,SYDNEY,NSW 2052,AUSTRALIA. NR 32 TC 10 Z9 11 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG PY 1995 VL 231 IS 3 BP 659 EP 666 DI 10.1111/j.1432-1033.1995.0659d.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RN395 UT WOS:A1995RN39500019 PM 7544282 ER PT J AU GAO, CY ZELENKA, PS AF GAO, CY ZELENKA, PS TI INDUCTION OF CYCLIN-B AND H1 KINASE-ACTIVITY IN APOPTOTIC PC12 CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID NERVE GROWTH-FACTOR; PHEOCHROMOCYTOMA CELLS; PROTEIN-KINASES; CHAIN-REACTION; CDC2 KINASE; DEATH; DNA; POLYMERASE; EVENTS; INVITRO AB The present study examines whether cyclin B may be involved in apoptosis of neuronally differentiated PC12 cells following withdrawal of NGF. Cyclin B mRNA increased approximately 10-fold 4 days after NGF withdrawal, as indicated by competitive RT/PCR. Sequencing of the PCR product confirmed that it was derived from cyclin B mRNA cyclin B protein increased in parallel with cyclin B mRNA, as shown by immunoblotting. Immunoprecipitation with anti-cyclin B antibody demonstrated that cyclin B was associated with H1K activity, which reached a maximum 5 days after NGF withdrawal. When proteins immunoprecipitated with anti-cyclin B antibody were immunoblotted with anti-PSTAIR antibody, a protein with apparent molecular weight of 34 kDa was detected. This protein was identified as p34(cdc2) On the basis of immunoreactivity with antibody against the C-terminal portion of mouse p34(cdc2). Since cyclin B/p34(cdc2) complexes are known to catalyze chromosomal condensation and nuclear envelope breakdown during mitosis, these results suggest that cyclin B/p34(cdc2) may play some role in the nuclear changes accompanying apoptosis of PC12 cells. (C) 1995 Academic Press, Inc. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 42 TC 56 Z9 58 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG PY 1995 VL 219 IS 2 BP 612 EP 618 DI 10.1006/excr.1995.1271 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA RQ063 UT WOS:A1995RQ06300038 PM 7641812 ER PT J AU KAPUR, R XIAO, XL COOPER, R RESNICK, J DONOVAN, PJ WILLIAMS, DA AF KAPUR, R XIAO, XL COOPER, R RESNICK, J DONOVAN, PJ WILLIAMS, DA TI SPLICING DEFECT OF THE KIT-LIGAND CYTOPLASMIC TAIL IN STEEL(17H) MICE RESULTS IN DIMINISHED CELL-ASSOCIATE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,HOWARD HUGHES MED INST,WELLS CTR PEDIAT RES,INDIANAPOLIS,IN. NCI,ABL,BASIC RES PROGRAM,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 748 EP 748 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600022 ER PT J AU ORLIC, D GIRARD, L LEE, D ANDERSON, S PUCK, J BODINE, D AF ORLIC, D GIRARD, L LEE, D ANDERSON, S PUCK, J BODINE, D TI DIFFERENTIAL EXPRESSION OF INTERLEUKIN-2 RECEPTOR-GAMMA (GAMMA(COMMON)) AND ITS PARTNERS, IL-2R, IL-4R, IL-7R, IL-9R, IN DEVELOPING THYMOCYTES AND BONE-MARROW OF MICE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCHGR,GENE TRANSFER LAB,IMMUNOL GENET SECT,BETHESDA,MD. NCHGR,GENE TRANSFER LAB,HEMATOPOIESIS SECT,BETHESDA,MD. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 820 EP 820 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600273 ER PT J AU ROZEMULLER, H ROMBOUTS, WJC GAISER, JF TOUW, IP FITZGERALD, DJP KREITMAN, RJ PASTAN, I HAGENBEEK, A MARTENS, ACM AF ROZEMULLER, H ROMBOUTS, WJC GAISER, JF TOUW, IP FITZGERALD, DJP KREITMAN, RJ PASTAN, I HAGENBEEK, A MARTENS, ACM TI SPECIFIC IN-VIVO TARGETING OF ACUTE MYELOCYTIC-LEUKEMIA CELLS WITH IL-6 PSEUDOMONAS EXOTOXIN SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,INST HEMATOL,ROTTERDAM,NETHERLANDS. DR DANIEL DEN HOED CANC CTR,3008 AE ROTTERDAM,NETHERLANDS. NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 836 EP 836 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600327 ER PT J AU GRZEGORZEWSKI, KJ KOMSCHLIES, KL RUSCETTI, FW KELLER, JR WILTROUT, RH AF GRZEGORZEWSKI, KJ KOMSCHLIES, KL RUSCETTI, FW KELLER, JR WILTROUT, RH TI MOBILIZATION OF PROGENITORS AND LONG-TERM REPOPULATING STEM-CELLS BY RECOMBINANT HUMAN INTERLEUKIN-7 (RHIL-7) ALONE OR IN COMBINATION WITH RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 848 EP 848 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600365 ER PT J AU DELWEL, R HOL, S VANKAN, Y LOWENBERG, B IHLE, JN COPELAND, NG VALK, P AF DELWEL, R HOL, S VANKAN, Y LOWENBERG, B IHLE, JN COPELAND, NG VALK, P TI THE CANNABINOID RECEPTOR-2 IS A POTENTIAL ONCOGENE IN MYELOID MOUSE LEUKEMIAS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM, INST HEMATOL, ROTTERDAM, NETHERLANDS. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN USA. NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 849 EP 849 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600367 ER PT J AU BOCK, TA ORLIC, D DUNBAR, CE BROXMEYER, HE BODINE, DM AF BOCK, TA ORLIC, D DUNBAR, CE BROXMEYER, HE BODINE, DM TI IMPROVED ENGRAFTMENT OF HUMAN HEMATOPOIETIC-CELLS IN SCID MICE CARRYING HUMAN CYTOKINE GENES AND IN NON OBESE-DIABETIC SCID MICE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,HEMATOPOIESIS SECT,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. UNIV TUBINGEN,MED KLIN,W-7400 TUBINGEN,GERMANY. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 8 BP 939 EP 939 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP116 UT WOS:A1995RP11600694 ER PT J AU JACOBSEN, FW KELLER, JR RUSCETTI, FW VEIBY, OP JACOBSEN, SEW AF JACOBSEN, FW KELLER, JR RUSCETTI, FW VEIBY, OP JACOBSEN, SEW TI DIRECT SYNERGISTIC EFFECTS OF IL-4 AND IL-11 ON PROLIFERATION OF PRIMITIVE HEMATOPOIETIC PROGENITOR CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE IL-4; IL-11; MYELOPOIESIS ID STIMULATORY FACTOR-I; STEM-CELLS; COLONY FORMATION; MURINE HEMATOPOIESIS; GROWTH-FACTORS; BONE-MARROW; HPP-CFC; T-CELL; INTERLEUKIN-11; CULTURE AB The present studies have investigated, for the first time, the synergistic effects of interleukin-4 (IL-4) and IL-11 on the growth of single murine bone marrow progenitor cells. These studies suggest that IL-4 and IL-11 are synergistic hematopoietic growth factors, enhancing colony formation of bone marrow progenitors from normal mice in the presence of colony-stimulating factors or stem cell factor, whereas neither IL-4 nor IL-11, alone or in combination, resulted in colony formation. However, in the presence of a neutralizing anti-TGF-beta antibody, IL-11 plus IL-4 induced clonal growth of primitive Lin(-)Sca-1(+) progenitors. Furthermore, here we report several observations extending the knowledge about IL-4 and IL-11 as synergistic factors. In addition to the established ability of IL-11 to enhance IL-3- and GM-CSF-induced colony formation, IL-11 also enhanced the number of G-CSF- and CSF-1-stimulated colonies of mature (Lin(-)) and primitive (Lin(-)Sca-1(+)) hematopoietic progenitors cultured at the single-cell level. In contrast, IL-4 bifunctionally regulated the growth of Lin(-) progenitors, whereas the growth of single Lin(-)Sca-1(+) progenitors was unaffected or enhanced in the presence of IL-4. Finally, IL-4 and IL-11, in combination, potently synergized to enhance the high-proliferative-potential colony-forming cell colony formation of Lin(-)Sca-1(+) progenitors in response to all four CSFs and to SCF. C1 PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NYCOMED AS,BIOREG,N-0371 OSLO,NORWAY. RP JACOBSEN, FW (reprint author), NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT IMMUNOL,N-0310 OSLO,NORWAY. NR 30 TC 8 Z9 9 U1 0 U2 0 PU CARDEN JENNINGS PUBL COLTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1995 VL 23 IS 9 BP 990 EP 995 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA RP118 UT WOS:A1995RP11800006 PM 7543420 ER PT J AU PERHAM, RN TERRY, TD WILLIS, AE GREENWOOD, J VERONESE, FD APPELLA, E AF PERHAM, RN TERRY, TD WILLIS, AE GREENWOOD, J VERONESE, FD APPELLA, E TI ENGINEERING A PEPTIDE EPITOPE DISPLAY SYSTEM ON FILAMENTOUS BACTERIOPHAGE SO FEMS MICROBIOLOGY REVIEWS LA English DT Article; Proceedings Paper CT EMBO-FEMS Meeting on Bacterial Viruses - Molecular Biology and Biotechnology CY MAR 27-30, 1994 CL GARGNANO, ITALY SP EMBO, Federat European Microbiol Soc DE FILAMENTOUS BACTERIOPHAGE; PHAGE DISPLAY; PEPTIDE EPITOPE; STRUCTURAL MIMICRY; HIVGP120; VACCINE DESIGN ID FOREIGN PEPTIDES; COAT PROTEIN; MULTIPLE DISPLAY; PHAGE; LIBRARIES; ANTIBODY; ENVELOPE; SURFACE; VACCINE; FUSION AB The genome of bacteriophage fd has been engineered to allow foreign amino acid sequences to be displayed in the exposed N-terminal segment of the major coat protein in the virus particle: small peptides can be encoded directly; larger peptides are encoded in hybrid virions, in which wild-type coat protein subunits are interspersed with coat proteins displaying the foreign peptides. Biophysical techniques, such as X-ray diffraction, indicate that the inclusion of the peptides can be achieved without significant disturbance to the helical parameters that define the protein-protein interactions in the assembled virion and the exposure of the peptides can be Verified by analysing the susceptibility to attack by proteolytic enzymes. Peptide sequences from the V3 loop of the surface glycoprotein gp120 of HIV-1 strain MN (HIV-1(MN)) displayed in this way are remarkably effective structural mimics of the natural epitope. They are recognised by human HIV antisera and evoke high titres of virus-neutralizing antibodies in mice. Antibody production is stimulated by simultaneous inoculation with T cell epitopes similarly displayed on filamentous bacteriophage. The bacteriophage display system offers a powerful means of studying the immunological recognition of proteins. The specificity of the immune response, the ability to recruit helper T cells, the lack of need for external adjuvants and the structural mimicry of defined peptide epitopes, suggest that it will also be an inexpensive and simple route to the production of effective vaccines. C1 ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP PERHAM, RN (reprint author), UNIV CAMBRIDGE,DEPT BIOCHEM,CAMBRIDGE CTR MOLEC RECOGNIT,TENNIS COURT RD,CAMBRIDGE CB2 1QW,ENGLAND. NR 33 TC 33 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD AUG PY 1995 VL 17 IS 1-2 BP 25 EP 31 PG 7 WC Microbiology SC Microbiology GA RT110 UT WOS:A1995RT11000003 PM 7545410 ER PT J AU DAVIS, CD SNYDERWINE, EG AF DAVIS, CD SNYDERWINE, EG TI PROTECTIVE EFFECT OF N-ACETYLCYSTEINE AGAINST HETEROCYCLIC AMINE-INDUCED CARDIOTOXICITY IN CULTURED MYOCYTES AND IN RATS SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID OXYGEN FREE-RADICALS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; LIPID-PEROXIDATION; CARDIAC TOXICITY; METABOLIC-ACTIVATION; COVALENT BINDING; DNA ADDUCTS; DOXORUBICIN; ADRIAMYCIN; CARCINOGEN AB Cooked meat contains many mutagenic/carcinogenic heterocyclic amines (HAs), including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The reactive N-hydroxylamine metabolites N-hydroxy-IQ and N-hydroxy-PhIP are toxic to isolated rat cardiomyocytes. This study examined whether antioxidant agents protect against N-hydroxyiamine-induced cardiotoxicity. In isolated rat cardiomyocytes, N-acetylcysteine, alpha-tocopherol and glutathione were protective against N-hydroxylamine-mediated lactate dehydrogenase release into the medium, suggesting that a free radical mechanism may be partly involved in HA-induced cardiotoxicity. Since N-acetylcysteine was by far the most protective of the agents investigated, the effects of N-acetylcysteine on HA-induced ultrastructural damage were further examined both in vitro and in vivo. Isolated cardiomyocytes treated with 1.2 mM N-acetylcysteine before and during exposure to N-hydroxy-IQ or N-hydroxy-PhIP showed a smaller percentage of ultrastructural abnormalities, such as myofilament loss, sarcoplasmic reticulum swelling and abnormal mitochondria. N-Acetylcysteine pretreatment also significantly reduced the percentage of cardiac cells with T-tubule dilation and myelin figures in adult rats dosed with IQ. The protective effect of N-acetylcysteine was not associated with a reduction in HA-DNA adducts, as assessed by P-32-postlabelling analysis of DNA from isolated cardiomyocytes treated with N-hydroxylamines. DNA adduct formation per se, therefore, may not be associated with the observed cardiotoxic effects of the HAs. Further studies are required to confirm the involvement of a free radical mechanism in HA cardiotoxicity. RP DAVIS, CD (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 48 TC 10 Z9 10 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 1995 VL 33 IS 8 BP 641 EP & DI 10.1016/0278-6915(95)00033-X PG 0 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA RV463 UT WOS:A1995RV46300003 PM 7672737 ER PT J AU CHAPIN, RE FAIL, PA GEORGE, JD GRIZZLE, TB HEINDEL, JJ HARRY, GJ COLLINS, BJ TEAGUE, J AF CHAPIN, RE FAIL, PA GEORGE, JD GRIZZLE, TB HEINDEL, JJ HARRY, GJ COLLINS, BJ TEAGUE, J TI THE REPRODUCTIVE AND NEURAL TOXICITIES OF ACRYLAMIDE AND 3 ANALOGS IN SWISS MICE, EVALUATED USING THE CONTINUOUS BREEDING PROTOCOL SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID CD-1 MICE; RATS; FERTILITY; NEUROTOXICITY; TOXICOLOGY; AGENTS; MOUSE AB Acrylamide is a known genetic, reproductive, and neural toxicant, although it is not known if one effect is predominant. The toxicities of several structural analogues of acrylamide have been incompletely characterized, and the relative sensitivity of the second generation is not known. The present studies were designed to explore the relationship between neurotoxicity and reproductive toxicity, to further characterize the toxicities of three acrylamide analogues, and to evaluate the relative sensitivity of a second generation to these compounds. For the Fo generation, male and female Swiss CD-1 mice were provided drinking water containing acrylamide (ACR; 3, 10, 30 ppm), N,N'-methylenebisacrylamide (MBA; 10, 30, 60 ppm), N-(hydroxymethyl)acrylamide (HMA; 60, 180, 360 ppm), or methacrylamide (MACR; 24, 80, 240 ppm) during and after a 14-week cohabitation. The last litter was reared and dosed after weaning until mating at 74 +/- 10 days of age with the same level of compound given to the parents. Neurotoxicity was assessed at several times in both generations by measuring forelimb and hindlimb grip strength. In the F-0 generation, ACR caused an 11% decrease in pup number without measurable neurotoxicity; female fertility was not affected. Although both generations consumed the same amount of ACR, there were larger changes in the fertility-related endpoints in the F-1 mice than in the F-0's, with no concomitant change in organ weights or sperm parameters. In F-0 mice, MBA reduced the number of live pups and their adjusted weight, with no neurotoxicity and no change in F-0 female reproduction. MBA caused greater adverse effects in the second generation, concomitant with increased consumption. In the Fo generation, HMA caused the largest decrease in pup number during cohabitation (26%) together with a small effect on grip strength. Female reproduction was not affected. The second generation consumed more HMA and showed slightly greater toxic effects. In both generations, MACR was negative for both neurotoxicity and reproductive toxicity. Dominant-lethal studies showed that the fertility effects for ACR, MBA, and HMA could be explained by a male-mediated increase in postimplantation loss. These studies found that dominant lethality occurred without structural effects on the reproductive system in the presence of only minor effects on grip strength and without detectable neural histopathology. Female reproduction was not significantly affected by these compounds at the doses used. Thus, these data confirm the male as the affected gender and that the reproductive toxicity was greater than motoneuron toxicity when measured as grip strength. (C) 1995 Society of Toxicology. C1 RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,RES TRIANGLE PK,NC 27709. ANALYT SCI INC,DURHAM,NC 27713. RP CHAPIN, RE (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-65141] NR 31 TC 30 Z9 30 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD AUG PY 1995 VL 27 IS 1 BP 9 EP 24 DI 10.1006/faat.1995.1104 PG 16 WC Toxicology SC Toxicology GA RN522 UT WOS:A1995RN52200002 PM 7589932 ER PT J AU CHAPIN, RE HARRIS, MW HUNTER, ES DAVIS, BJ COLLINS, BJ LOCKHART, AC AF CHAPIN, RE HARRIS, MW HUNTER, ES DAVIS, BJ COLLINS, BJ LOCKHART, AC TI THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF INDIUM IN THE SWISS MOUSE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID BORIC-ACID; CHLORIDE; EMBRYOS; MICE; RAT AB Indium is increasingly used in a variety of industries, and while there are few studies of its developmental toxicity, there are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to determine the relative vulnerability of males and females. We used, initially, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl3 (less than or equal to 250 mg/kg) were without effect on the male reproductive system or liver. A kidney effect was demonstrated in males by a decrease in urinary N-acetyl glucosaminidase. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intrauterine deaths in the presence of reduced maternal weight gain. A developmental toxicity study identified no increase in fetal malformations, but verified the increased fetal deaths, in the absence of effects on adjusted maternal body weight. In vitro toxicity studies showed that the embryolethality was at least in part a result of direct toxicity to the conceptus, with effective doses in the low micromolar range. A limited disposition study showed that fetuses contained low micromolar concentrations of indium, more indium than maternal liver, and comparable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicate that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low micromolar levels in vivo and at exposures that may or may not affect body weight. (C) 1995 Society of Toxicology. C1 NIEHS,NATL TOXICOL PROGRAM,CHEM GRP,RES TRIANGLE PK,NC 27709. ANALYT SCI INC,RES TRIANGLE PK,NC 27709. RP CHAPIN, RE (reprint author), NIEHS,REPROD TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-15307] NR 22 TC 27 Z9 30 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD AUG PY 1995 VL 27 IS 1 BP 140 EP 148 DI 10.1006/faat.1995.1117 PG 9 WC Toxicology SC Toxicology GA RN522 UT WOS:A1995RN52200015 PM 7589924 ER PT J AU CONJEEVARAM, HS HOOFNAGLE, JH AUSTIN, HA PARK, Y FRIED, MW DIBISCEGLIE, AM AF CONJEEVARAM, HS HOOFNAGLE, JH AUSTIN, HA PARK, Y FRIED, MW DIBISCEGLIE, AM TI LONG-TERM OUTCOME OF HEPATITIS-B VIRUS-RELATED GLOMERULONEPHRITIS AFTER THERAPY WITH INTERFERON-ALFA SO GASTROENTEROLOGY LA English DT Article ID MEMBRANOUS GLOMERULONEPHRITIS; SURFACE-ANTIGEN; ALPHA-INTERFERON; NEPHROPATHY; DEPOSITION; INFECTION; CHILDREN; ADULTS; GLOMERULOPATHY; IMPROVEMENT AB Background and Aims: Glomerulonephritis is an uncommon complication of chronic hepatitis B virus (HBV) infection in adults. A high percentage of patients seem to have short-term response to interferon therapy with improvement of proteinuria. The aim of this study was to assess the long-term response of patients with HBV-related glomerulonephritis to interferon alfa therapy. Methods: All patients with chronic hepatitis 8 and glomerulonephritis who were treated with interferon alfa at the National Institutes of Health between 1985 and 1993 were assessed. Results: Of the 15 patients treated, 8 (53%) had a long term serological response with sustained loss of serum hepatitis 8 e antigen and HBV DNA. After 1-7 years of follow-up, all 8 responders have normal serum amino-transferase transferase levels and 5 are hepatitis 8 surface antigen negative. Seven of the responders also showed a gradual but marked improvement in proteinuria. In contrast, the 7 nonresponders continued to have evidence of active renal disease and 1 required long-term dialysis therapy. All 8 responders had membranous glomerulonephritis, whereas 4 of 7 nonresponders had membranoproliferative glomerulonephritis. Conclusions: Interferon alfa therapy resulted in long-term remission in liver disease in 8 of 15 patients with chronic hepatitis B and glomerulonephritis. This response was accompanied by significant improvement in markers of renal disease in the majority of patients. C1 NIH,DEPT NURSING,BETHESDA,MD. NIDDK,KIDNEY DIS SECT,BETHESDA,MD 20892. RP CONJEEVARAM, HS (reprint author), NIDDK,DIGEST DIS BRANCH,LIVER DIS SECT,ROOM 4D-52,BLDG 10,10 CTR DR,MSC 1372,BETHESDA,MD 20892, USA. NR 34 TC 56 Z9 61 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 1995 VL 109 IS 2 BP 540 EP 546 DI 10.1016/0016-5085(95)90343-7 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RM508 UT WOS:A1995RM50800025 PM 7615204 ER PT J AU FRAGOSO, G JOHN, S ROBERTS, MS HAGER, GL AF FRAGOSO, G JOHN, S ROBERTS, MS HAGER, GL TI NUCLEOSOME POSITIONING ON THE MMTV LTR RESULTS FROM THE FREQUENCY-BIASED OCCUPANCY OF MULTIPLE FRAMES SO GENES & DEVELOPMENT LA English DT Article DE MMTV LTR; NUCLEOSOME POSITIONING; PHASING; FREQUENCY-BIASED OCCUPANCY; TRANSLATIONAL FRAMES; HISTONE OCTAMER ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; MICROCOCCAL NUCLEASE; CHROMATIN STRUCTURE; SACCHAROMYCES-CEREVISIAE; DNASE-I; PROMOTER; SEQUENCE; TRANSCRIPTION; EXPRESSION AB The translational positions of nucleosomes in the promoter region of the mouse mammary tumor virus (MMTV) were defined at high resolution. Nucleosome boundaries were determined in primer extension assays using full-length single-stranded mononucleosomal DNA prepared from cells treated with formaldehyde, a reversible protein-DNA cross-linking agent. Multiple boundaries were observed in both the nucleosome A (Nuc-A) and Nuc-B region of the promoter, indicating multiple nucleosome translational frames. The different nucleosome frames in both the Nuc-A and Nuc-B regions were occupied unequally. The most frequently occupied frames were found clustered within 50-60 bases of each other, resulting in a distribution centered in the positions defined previously at low resolution for Nuc-A and Nuc-B. The most abundant 5' ends of the frames in the B region were found between -235 and -187, and the 3' ends between -86 and -36, whereas in the A region the most abundant 5' ends were between -22 and +42, and the 3' ends between +121 and +186. Although frames in the Nuc-B region of the LTR extend at a low frequency in the 5' direction toward the Nuc-C region, there is a sharp discontinuity in the 3' direction toward Nuc-A, suggesting the presence of a boundary constraint in the A-B linker. The positions and relative occupancies of nucleosome frames, in either the B or the A region, did not change when the promoter was activated with dexamethasone. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 62 TC 149 Z9 150 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 AUG 1 PY 1995 VL 9 IS 15 BP 1933 EP 1947 DI 10.1101/gad.9.15.1933 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RQ218 UT WOS:A1995RQ21800011 PM 7649476 ER PT J AU MAI, S HANLEYHYDE, J COLEMAN, A SIWARSKI, D HUPPI, K AF MAI, S HANLEYHYDE, J COLEMAN, A SIWARSKI, D HUPPI, K TI AMPLIFIED EXTRACHROMOSOMAL ELEMENTS CONTAINING C-MYC AND PVT-1 IN A MOUSE PLASMACYTOMA SO GENOME LA English DT Article DE AMPLIFICATION; C-MYC; PVT 1; PLASMACYTOMA ID GENE AMPLIFICATION; TUMOR-CELLS; DNA-SEQUENCES; TRANSLOCATIONS; CHROMOSOMES; LEUKEMIA; REGION; LINES AB After adaptation of a mouse plasma cell tumor, MOPC265, to culture, we have found several unique chromosomal alterations in addition to the T(12;15) translocation and trisomy 11 frequently observed in plasmacytomas. Among these alterations is a specific coamplification of the c-Myc and Pvt I gene loci from mouse chromosome 15. Further analysis by fluorescence in situ hybridization demonstrates that the amplicons of c-Myc and Pvt I exist as extrachromosomal elements as well as within intact chromosomes. Most importantly, the presence of both Pvt I and c-Myc in these extrachromosomal elements indicates ongoing coselection for these loci in the propagation of MOPC265. C1 NCI, GENET LAB, MOLEC GENET SECT, BETHESDA, MD 20892 USA. BASEL INST IMMUNOL, CH-4005 BASEL, SWITZERLAND. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. RI Mai, Sabine/E-5667-2017 OI Mai, Sabine/0000-0002-5797-2201 NR 27 TC 9 Z9 9 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0831-2796 J9 GENOME JI Genome PD AUG PY 1995 VL 38 IS 4 BP 780 EP 785 DI 10.1139/g95-099 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RR174 UT WOS:A1995RR17400020 PM 7672608 ER PT J AU GREEN, ED MAFFEI, M BRADEN, VV PROENCA, R DESILVA, U ZHANG, YY CHUA, SC LEIBEL, RL WEISSENBACH, J FRIEDMAN, JM AF GREEN, ED MAFFEI, M BRADEN, VV PROENCA, R DESILVA, U ZHANG, YY CHUA, SC LEIBEL, RL WEISSENBACH, J FRIEDMAN, JM TI THE HUMAN OBESE (OB) GENE - RNA EXPRESSION PATTERN AND MAPPING ON THE PHYSICAL, CYTOGENETIC, AND GENETIC MAPS OF CHROMOSOME-7 SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME PROJECT; POSITIONAL CLONING; CONSTRUCTION; LIBRARIES; FAMILY; PAX AB The recently identified mouse obese [ob] gene apparently encodes a secreted protein that may function in the signaling pathway of adipose tissue. Mutations in the mouse ob gene are associated with the early development of gross obesity. A detailed knowledge concerning the RNA expression pattern and precise genomic location of the human homolog, the OB gene, would facilitate examination of the role of this gene in the inheritance of human obesity. Northern blot analysis revealed that OB RNA is present at a high level in adipose tissue but at much lower levels in placenta and heart. OB RNA is undetectable in a wide range of other tissues. Comparative mapping of mouse and human DNA indicated that the ob gene is located within a region of mouse chromosome 6 that is homologous to a portion of human chromosome 7q. We mapped the human OB gene on a yeast artificial chromosome [YAC] contig from chromosome 7q31.3 that contains 43 clones and 19 sequence-tagged sites [STSs]. Among the 19 STSs are eight corresponding to microsatellite-type genetic markers, including seven [CA](n) repeat-type Genethon markers. Because of their close physical proximity to the human OB gene, these eight genetic markers represent valuable tools for analyzing families with evidence of hereditary obesity and for investigating the possible association between OB mutations and human obesity. C1 HOWARD HUGHES MED INST,NEW YORK,NY 10021. HUMAN BEHAV & METAB LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,NEW YORK,NY 10021. GENETHON,F-91000 EVRY,FRANCE. INST PASTEUR,UNITE GENET MOLEC HUMAINE,CNRS,URA 1445,F-75724 PARIS,FRANCE. RP GREEN, ED (reprint author), NIA,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [P50-HG00201]; NICHD NIH HHS [HD 28047]; NIDDK NIH HHS [DK 41906] NR 26 TC 146 Z9 148 U1 0 U2 5 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 AUG PY 1995 VL 5 IS 1 BP 5 EP 12 DI 10.1101/gr.5.1.5 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ816 UT WOS:A1995RQ81600002 PM 8717050 ER PT J AU PAVAN, WJ MAC, S CHENG, M TILGHMAN, SM AF PAVAN, WJ MAC, S CHENG, M TILGHMAN, SM TI QUANTITATIVE TRAIT LOCI THAT MODIFY THE SEVERITY OF SPOTTING IN PIEBALD MICE SO GENOME RESEARCH LA English DT Article ID TYROSINE KINASE RECEPTOR; CELL GROWTH-FACTOR; W-LOCUS; NORMAL MELANOCYTES; MENDELIAN FACTORS; PROTO-ONCOGENE; LINKAGE MAP; KIT LIGAND; SI-LOCUS; MOUSE AB Mice homozygous for the recessive mutation piebald [s] exhibit a white-spotted coat caused by the defective development of neural crest-derived melanocytes. The severity of white spotting varies greatly, depending on the genetic background on which s is expressed. A backcross between two inbred strains of s/s mice that exhibit large differences in the degree of spotting was used to identify six genetic modifiers of piebald spotting on chromosomes 2, 5, 7, 8, 10, and 13. The loci differed in their spatial contribution to spotting on the dorsal versus ventral surfaces of mice; nonadditive interactions were observed between loci on chromosomes 2 and 5. This study underscores the power of using genetic analyses to identify and analyze loci involved in modifying the severity of phenotypic traits in mice. C1 PRINCETON UNIV,HOWARD HUGHES MED INST,PRINCETON,NJ 08544. NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. RP PAVAN, WJ (reprint author), PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544, USA. NR 53 TC 45 Z9 45 U1 1 U2 4 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 AUG PY 1995 VL 5 IS 1 BP 29 EP 41 DI 10.1101/gr.5.1.29 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ816 UT WOS:A1995RQ81600005 PM 8717053 ER PT J AU AI, YJ JENKINS, NA COPELAND, NG GILBERT, DJ BERGSMA, DJ STAMBOLIAN, D AF AI, YJ JENKINS, NA COPELAND, NG GILBERT, DJ BERGSMA, DJ STAMBOLIAN, D TI MOUSE GALACTOKINASE - ISOLATION, CHARACTERIZATION, AND LOCATION ON CHROMOSOME-11 SO GENOME RESEARCH LA English DT Article ID THYMIDINE KINASE; MUS-MUSCULUS; GAL OPERON; GENE; ASSIGNMENT; ORGANIZATION; SEQUENCES; CLONING; REGION; MAP AB Elevated galactose levels can be caused by several is galactokinase. Galactokinase deficiency causes congenital cataracts during infancy and presenile cataracts in the adult population. We have isolated the mouse cDNA for galactokinase, which shares extensive amino acid sequence homology 88% identity, with a recently cloned human galactokinase. It is expressed in all tissues examined. In an interspecific backcross analysis galactokinase maps to the distal region of mouse chromosome 11, a region that is homologous to human chromosome 17q22-25. The availability of the mouse gene provides an opportunity to make a knockout model for galactokinase deficiency. C1 UNIV PENN,SCH MED,DEPT OPHTHALMOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. SMITHKLINE BEECHAM PHARMACEUT,DEPT MOLEC GENET,KING OF PRUSSIA,PA 19406. FU NCI NIH HHS [N01-CO-46000]; NEI NIH HHS [R01 EY09404] NR 24 TC 13 Z9 15 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 AUG PY 1995 VL 5 IS 1 BP 53 EP 59 DI 10.1101/gr.5.1.53 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RQ816 UT WOS:A1995RQ81600007 PM 8717055 ER PT J AU MARTIN, GR BAKER, GT AF MARTIN, GR BAKER, GT TI GENES AND AGING - KANUNGO,MS SO GERONTOLOGIST LA English DT Book Review ID MITOCHONDRIAL-DNA; CELLS C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP MARTIN, GR (reprint author), FIBROGEN INC,SCI AFFAIRS,772 LUCERNE DR,SUNNYVALE,CA 94086, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 1995 VL 35 IS 4 BP 564 EP 565 PG 2 WC Gerontology SC Geriatrics & Gerontology GA RY656 UT WOS:A1995RY65600018 ER PT J AU FOZARD, JL BAKER, GT AF FOZARD, JL BAKER, GT TI BIOLOGICAL ANTHROPOLOGY AND AGING - PERSPECTIVES ON HUMAN VARIATION OVER THE LIFE-SPAN - CREWS,DE, GARRUTO,RM SO GERONTOLOGIST LA English DT Book Review RP FOZARD, JL (reprint author), NIA,HOPKINS BAYVIEW MED CTR,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Fozard, James Leonard/B-3660-2009 NR 1 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 1995 VL 35 IS 4 BP 566 EP 567 PG 2 WC Gerontology SC Geriatrics & Gerontology GA RY656 UT WOS:A1995RY65600020 ER PT J AU SPROTT, RL BAKER, GT AF SPROTT, RL BAKER, GT TI HUMAN LONGEVITY - SMITH,DWE SO GERONTOLOGIST LA English DT Book Review C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP SPROTT, RL (reprint author), NIA,BIOL AGING PROGRAM,GATEWAY BLDG,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 1995 VL 35 IS 4 BP 566 EP 566 PG 1 WC Gerontology SC Geriatrics & Gerontology GA RY656 UT WOS:A1995RY65600019 ER PT J AU Israel, BA Cummings, KM Dignan, MB Heaney, CA Perales, DP SimonsMorton, BG Zimmerman, MA AF Israel, BA Cummings, KM Dignan, MB Heaney, CA Perales, DP SimonsMorton, BG Zimmerman, MA TI Evaluation of health education programs: Current assessment and future directions SO HEALTH EDUCATION QUARTERLY LA English DT Article; Proceedings Paper CT Research Meeting on Creating Capacity - Establishing a Health Education Research Agenda CY SEP 25-27, 1994 CL ATLANTA, GA SP Soc Public Hlth Educ, Ctr Dis Control & Prevention ID PHYSICAL-ACTIVITY; CERVICAL-CANCER; FORSYTH COUNTY; PROMOTION; CARE; PREVENTION; CHILDREN; PROJECT; PERSPECTIVE; EMPOWERMENT AB Recently there has been an increase in the different types of strategies used in health education interventions, including an emphasis on broadening programs focused on individual behavior change to include larger units of practice. There has also been an increasing critique of the traditional physical science paradigm for evaluating the multiple dimensions inherent in many interventions. Additionally, there is a growing recognition of the importance of involving multiple stakeholders in designing, implementing, and evaluating interventions. Each of these factors carries specific evaluation challenges. With the overall aim of strengthening the evaluation of health education programs, this article aims to (a) present conceptual and technical design issues and options, (b) describe different approaches to evaluation, (c) highlight evaluation approaches that have been effective, (d) critique the limitations of traditional evaluation approaches, (e) examine promising approaches and implications for future evaluations, and (f) provide recommendations for evaluation designs, data collection methods, roles, responsibilities, and principles for evaluating interventions. C1 ROSWELL PK CANC INST,DEPT CANC CONTROL & EPIDEMIOL,BUFFALO,NY. BOWMAN GRAY SCH MED,DEPT FAMILY & COMMUNITY HLTH,WINSTON SALEM,NC. OHIO STATE UNIV,DEPT PREVENT MED,COLUMBUS,OH 43210. SAN JOSE STATE UNIV,DEPT HLTH SCI,SAN JOSE,CA 95192. NICHHD,NIH,ROCKVILLE,MD. RP Israel, BA (reprint author), UNIV MICHIGAN,SCH PUBL HLTH,DEPT HLTH BEHAV & HLTH EDUC,1420 WASHINGTON HEIGHTS,ANN ARBOR,MI 48109, USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 113 TC 79 Z9 82 U1 14 U2 18 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD AUG PY 1995 VL 22 IS 3 BP 364 EP 389 PG 26 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UD811 UT WOS:A1995UD81100008 PM 7591790 ER PT J AU McLeroy, KR Clark, NM SimonsMorton, BG Forster, J Connell, CM Altman, D Zimmerman, MA AF McLeroy, KR Clark, NM SimonsMorton, BG Forster, J Connell, CM Altman, D Zimmerman, MA TI Creating capacity: Establishing a health education research agenda for special populations SO HEALTH EDUCATION QUARTERLY LA English DT Article; Proceedings Paper CT Research Meeting on Creating Capacity - Establishing a Health Education Research Agenda CY SEP 25-27, 1994 CL ATLANTA, GA SP Soc Public Hlth Educ, Ctr Dis Control & Prevention ID FOLLOW-UP; SMOKING; PERSPECTIVE; PREVENTION AB On Day 2 of the joint CDC/SOPHE conference on Creating Capacity: Establishing a Research Agenda for Health Education, the participants were asked to identify research needs or special issues in working with children and adolescents, the elderly, women, men, and underserved groups. This article presents the priority research areas across subgroups identified by the participants. The cross-group priorities are followed by research recommendations for each subgroup. C1 UNIV MICHIGAN,SCH PUBL HLTH,DEPT HLTH BEHAV & HLTH EDUC,ANN ARBOR,MI 48109. NICHHD,NIH,ROCKVILLE,MD. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV MICHIGAN,SCH PUBL HLTH,DEPT HLTH BEHAV & HLTH EDUC,ANN ARBOR,MI 48109. RP McLeroy, KR (reprint author), UNIV OKLAHOMA,COLL PUBL HLTH,DEPT HLTH PROMOT SCI,801 NE 13TH ST,ROOM 369,POB 26901,OKLAHOMA CITY,OK 73190, USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 31 TC 8 Z9 8 U1 1 U2 1 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD AUG PY 1995 VL 22 IS 3 BP 390 EP 405 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UD811 UT WOS:A1995UD81100009 PM 7591791 ER PT J AU MIZUTA, K IWASA, KH TACHIBANA, M BENOS, DJ LIM, DJ AF MIZUTA, K IWASA, KH TACHIBANA, M BENOS, DJ LIM, DJ TI AMILORIDE-SENSITIVE NA+ CHANNEL-LIKE IMMUNOREACTIVITY IN THE LUMINAL MEMBRANE OF SOME NONSENSORY EPITHELIA OF THE INNER-EAR SO HEARING RESEARCH LA English DT Article DE AMILORIDE-SENSITIVE NA+ CHANNEL; IMMUNOGOLD LABELING; STRIA VASCULARIS; SPIRAL PROMINENCE; AMPULLAR DARK CELL; REISSNERS MEMBRANE ID STRIA VASCULARIS; NONSELECTIVE CATION; APICAL MEMBRANE; SODIUM-CHANNEL; CL CHANNELS; DARK CELLS; K PUMP; LOCALIZATION; MECHANISMS; POTENTIALS AB Some non-sensory epithelia of the inner ear were examined for the localization of immunoreactivity to polyclonal antibodies raised against amiloride-sensitive Na+ channels from the bovine kidney. The pre-embedding immunogold technique was used for this purpose. Labelings were found on the membrane of the endolymphatic surface of strial marginal cells, epithelial cells of spiral prominence and Reissner's membrane, and ampullar dark cells. In contrast, no labeling was found on the luminal membrane of mesothelial cells of Reissner's membrane, the cells lining the supra-strial perilymphatic space, transitional cells and ampullar ceiling cells. Since the antibodies used may also label non-selective cation channels and non-functional sodium channel precursors as suggested by others, it was not possible to determine the labelings are solely due to amiloride-sensitive Na+ channels. However, the observed result was consistent with the previous studies that amiloride blocks ion transport in strial marginal cells and the semicircular canal. It is therefore likely that the observed labeling includes amiloride-sensitive Naf channels. These labeled ion channels in a variety of epithelial cells lining the endolymphatic space could be important in the inner ear fluid regulation. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS,CELLULAR BIOL LAB,BETHESDA,MD 20892. NATL INST DEAFNESS & OTHER COMMUN DISORDERS,GENET MOLEC LAB,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. OI Iwasa, Kuni/0000-0002-9397-7704 NR 29 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD AUG PY 1995 VL 88 IS 1-2 BP 199 EP 205 DI 10.1016/0378-5955(95)00113-I PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA TF523 UT WOS:A1995TF52300021 PM 8575996 ER PT J AU GONZALEZ, A ESTEBAN, JI MADOZ, P VILADOMIU, L GENESCA, J MUNIZ, E ENRIQUEZ, J TORRAS, X HERNANDEZ, JM QUER, J VIDAL, X ALTER, HJ SHIH, JW ESTEBAN, R GUARDIA, J AF GONZALEZ, A ESTEBAN, JI MADOZ, P VILADOMIU, L GENESCA, J MUNIZ, E ENRIQUEZ, J TORRAS, X HERNANDEZ, JM QUER, J VIDAL, X ALTER, HJ SHIH, JW ESTEBAN, R GUARDIA, J TI EFFICACY OF SCREENING DONORS FOR ANTIBODIES TO THE HEPATITIS-C VIRUS TO PREVENT TRANSFUSION-ASSOCIATED HEPATITIS - FINAL REPORT OF A PROSPECTIVE TRIAL SO HEPATOLOGY LA English DT Article ID NON-B-HEPATITIS; NON-A; POSTTRANSFUSION HEPATITIS; CIRCULATING ANTIBODIES; LIVER-DISEASE; BLOOD-DONORS; INFECTION; RISK; RECIPIENTS; ANTIGEN AB Routine screening of blood donors for anti-hepatitis C virus (HCV) has been implemented in most developed countries. However, the independent efficacy of such screening has not been established in a controlled, prospective study. We tracked 478 patients transfused with anti-HCV-negative blood by first-generation enzyme-linked immunoassay (EIA) between July 1989 and May 1990 and compared the incidence of transfusion-associated hepatitis and HCV infections with that found among 280 patients transfused with blood unscreened for anti-HCV during the immediately preceding year. Of the 280 patients who had received transfusions before donors were screened for anti-HCV, 27 (9.6%) developed posttransfusion hepatitis and 1 additional patient sero-converted to anti-HCV without evidence of hepatitis, for a risk of posttransfusion HCV infection of 10.7% (28 of 262 recipients seronegative for anti-HCV before transfusion). Of the 478 patients transfused after July 1989 with blood screened for anti-HCV, only 9 (1.9%) developed posttransfusion hepatitis for a risk reduction of 80%. Seven of the 9 residual cases of hepatitis were caused by HCV (7 of 456 recipients seronegative before transfusion or 1.5%) for a risk reduction of transfusion-associated HCV infection of 86%, in retrospect, an anti-HCV positive donor was detected by second-generation immunoassay in 4 (57%) of the 7 HCV cases from the study cohort and in 19 of the 23 (83%) cases from whom all donor samples were available for testing in the historical cohort. No additional infectious donors were detected by third-generation immunoassay or serum HCV-RNA by polymerase chain reaction. implementation of donor screening for anti-HCV with a first-generation immunoassay appeared to be independently associated with an 80% and 86% reduction in the risks of transfusion-associated hepatitis and HCV infection, respectively. Screening of donors with second-generation immunoassays might have further reduced the risk by 57%. An additional 0.4% may be at risk of developing non-A, non-B, non-C hepatitis. C1 HOSP GEN VALLE HEBRON,DEPT INTERNAL MED,LIVER UNIT,E-08035 BARCELONA,SPAIN. HOSP GEN VALLE HEBRON,CLIN PHARMACOL UNIT,E-08035 BARCELONA,SPAIN. INST CATALA SALUT,BLOOD BANK,BARCELONA,SPAIN. UNIV AUTONOMA BARCELONA,HOSP SANTA CRUZ & SAN PABLO,BLOOD BANK,BARCELONA,SPAIN. UNIV AUTONOMA BARCELONA,HOSP SANTA CRUZ & SAN PABLO,GASTROENTEROL UNIT,BARCELONA,SPAIN. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD. RI Quer, Josep/A-6741-2012; OI Vidal, Xavier/0000-0001-6705-4298; Genesca, Joan/0000-0002-0831-8422 NR 20 TC 33 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 1995 VL 22 IS 2 BP 439 EP 445 DI 10.1016/0270-9139(95)90563-4 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RM337 UT WOS:A1995RM33700010 PM 7635410 ER PT J AU SITZMANN, JV WU, YP AGUILERA, G CAHILL, PA BURNS, RC AF SITZMANN, JV WU, YP AGUILERA, G CAHILL, PA BURNS, RC TI LOSS OF ANGIOTENSIN-II RECEPTORS IN PORTAL HYPERTENSIVE RABBITS SO HEPATOLOGY LA English DT Article ID VASCULAR-RESPONSE; CIRRHOTIC RATS; NITRIC-OXIDE; PROSTACYCLIN; ANTAGONISTS; SUBTYPES; RENIN AB Decreased splanchnic vascular response to exogenous angiotensin-II (A-II) infusion in portal hypertension has recently been documented, A-II receptor density and binding affinity in the mesenteric artery, portal vein, and adrenal gland of normal and portal hypertensive rabbits were studied. Portal hypertension was induced by partial portal vein ligation 3 weeks before study, There were no significant differences in serum concentrations of sodium, potassium, A-II, serum osmolality, or hematocrit between normal and portal hypertensive rabbits, The portal hypertensive portal vein exhibited a 60% fall in A-II receptor number from 65.1 +/- 0.3 fmol/mg in normal to 27.0 +/- 8 fmol/mg (P < .05) in portal hypertension, A significant decrease in receptor number occurred in the portal hypertensive mesenteric artery, 224 +/- 39 fmol/mg compared with 345 +/- 45 fmol/mg in normal rabbits, and in the adrenal cortex 6.8 +/- 1.3 pmol/mg compared with 12.1 +/- 2.5 pmol/mg in normal controls (P < .05), No significant difference in A-II. receptor affinity was observed in tissues studied between normal and portal hypertensive rabbits, Autoradiographic study on A-II receptors was consistent with data from membrane binding assays, Receptor subtype analysis showed exclusive type I receptor binding in the mesenteric artery and portal vein. We conclude there is a global reduction in the A-II receptor number in portal hypertension that may mediate much of the decreased response to A-II seen in this disorder, This loss of the A-II receptor may partially explain hemodynamic derangements peculiar to portal hypertension. C1 JOHNS HOPKINS MED INST,DEPT SURG,BALTIMORE,MD 21205. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RI Cahill, Paul/E-8061-2011 OI Cahill, Paul/0000-0002-5385-6502 FU NHLBI NIH HHS [F32HL089078]; NIDDK NIH HHS [R01 DK47067] NR 26 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 1995 VL 22 IS 2 BP 559 EP 564 DI 10.1016/0270-9139(95)90580-4 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RM337 UT WOS:A1995RM33700027 PM 7635425 ER PT J AU SALLIE, R AF SALLIE, R TI HEPATITIS-C - IIB(IV) OR NOT IIB(IV) THAT IS THE QUESTION SO HEPATOLOGY LA English DT Note ID POLYMERASE CHAIN-REACTION; VIRUS; GENOTYPES; ENTRY; RNA RP SALLIE, R (reprint author), NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 1995 VL 22 IS 2 BP 671 EP 674 DI 10.1016/0270-9139(95)90597-9 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RM337 UT WOS:A1995RM33700044 PM 7635440 ER PT J AU WILLEMSEN, R TIBBE, JJM KROOS, MA MARTIN, BM REUSER, AJJ GINNS, EI AF WILLEMSEN, R TIBBE, JJM KROOS, MA MARTIN, BM REUSER, AJJ GINNS, EI TI A BIOCHEMICAL AND IMMUNOCYTOCHEMICAL STUDY ON THE TARGETING OF ALGLUCERASE IN MURINE LIVER SO HISTOCHEMICAL JOURNAL LA English DT Article ID HUMAN BETA-GLUCOCEREBROSIDASE; GAUCHERS-DISEASE; MONOCLONAL-ANTIBODIES; CELLS AB A current hypothesis is that functional glucocerebrosidase needs to be delivered to the lysosomes of tissue macrophages to guarantee successful enzyme therapy for Gaucher's disease. In this study, biochemical and immunohistochemical techniques were applied to identify in mice the localization of intravenously administered alglucerase (human modified placental glucocerebrosidase). Only in liver and spleen was a significant increase of glucocerebrosidase activity observed, with a maximum level at 15 minutes after enzyme infusion. The uptake of enzyme by liver was sufficiently high to allow more detailed studies on the (sub)cellular distribution of human alglucerase. The enzyme in liver is localized both in the endosomal-lysosomal system of the Kupffer cells and the endothelial cells lining the lumen of the sinusoids. Uptake by both of these types of cell is prevented by mannan. The results suggest that the cellular mechanisms responsible for improvement of Gaucher patients receiving alglucerase treatment is probably more complicated than previously recognized. C1 ERASMUS UNIV ROTTERDAM,DEPT IMMUNOL,3000 DR ROTTERDAM,NETHERLANDS. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP WILLEMSEN, R (reprint author), ERASMUS UNIV ROTTERDAM,DEPT CLIN GENET,3000 DR ROTTERDAM,NETHERLANDS. NR 20 TC 5 Z9 5 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD AUG PY 1995 VL 27 IS 8 BP 639 EP 646 PG 8 WC Cell Biology SC Cell Biology GA RP232 UT WOS:A1995RP23200011 PM 8550385 ER PT J AU BOST, M BERKAW, M MCBRIDE, OW CHAZOT, G ARNAUD, P AF BOST, M BERKAW, M MCBRIDE, OW CHAZOT, G ARNAUD, P TI RESTRICTION POLYMORPHISMS OF THE CERULOPLASMIN GENE ON CHROMOSOME-3 SO HUMAN GENETICS LA English DT Note AB Using a probe isolated from a human liver cDNA library, polymorphisms were observed in the human ceruloplasmin gene with the enzymes PstI and MspI. The PstI polymorphism was frequent (allele frequencies, 0.46 and 0.54) whereas the polymorphisms found with MspI were rare. C1 MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,GENET MOLEC LAB,CHARLESTON,SC 29425. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP BOST, M (reprint author), HOP IANTIQUAILLE,NEUROGENET LAB,1 RUE IANTIQUAILLE,F-69005 LYON,FRANCE. NR 7 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 1995 VL 96 IS 2 BP 239 EP 240 DI 10.1007/BF00207390 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA RK056 UT WOS:A1995RK05600023 PM 7635481 ER PT J AU LAUE, L WU, SM KUDO, M HSUEH, AJW CUTLER, GB GRIFFIN, JE WILSON, JD BRAIN, C BERRY, AC GRANT, DB CHAN, WY AF LAUE, L WU, SM KUDO, M HSUEH, AJW CUTLER, GB GRIFFIN, JE WILSON, JD BRAIN, C BERRY, AC GRANT, DB CHAN, WY TI A NONSENSE MUTATION OF THE HUMAN LUTEINIZING-HORMONE RECEPTOR GENE IN LEYDIG-CELL HYPOPLASIA SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; PRECOCIOUS PUBERTY; MALE PSEUDOHERMAPHRODITISM; CHORIONIC-GONADOTROPIN; CHORIOGONADOTROPIN; EXPRESSION; SURFACE; RAT; LH AB Leydig cell hypoplasia (LCH) is a form of male pseudohermaphroditism in which Leydig cell differentiation and testosterone production are impaired, This report describes the first case of a nonsense mutation (A1635C) in exon 11 of the human luteinizing hormone receptor (hLHR) gene in two sisters with LCH. This mutation causes loss of function of the receptor by introducing a stop codon at residue 545 in transmembrane helix 5 of the hLHR. Surface expression of the truncated hLHR (hLHR-t545) in human embryonic kidney cells stably transfected with cDNA encoding hLHR-t545 was diminished compared to the wild-type hLHR and hCG-induced cAMP accumulation was impaired, These results establish that single base mutations in exon 11 of the hLHR gene can produce inactivation as well as activation of the hLMR. Furthermore, they demonstrate that functional domains between transmembrane helix 5 and the C-terminal cytoplasmic tail of the hLHR are required for normal cell surface expression of the receptor and signal transduction. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL & BIOCHEM,WASHINGTON,DC 20007. STANFORD UNIV,MED CTR,DEPT OBSTET & GYNECOL,STANFORD,CA 94305. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT INTERNAL MED,DALLAS,TX 75235. GREAT ORMOND ST HOSP CHILDREN,LONDON,ENGLAND. GUYS HOSP,LONDON SE1 9RT,ENGLAND. RP LAUE, L (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007, USA. FU NICHD NIH HHS [HD-01109] NR 33 TC 84 Z9 85 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 AUG PY 1995 VL 4 IS 8 BP 1429 EP 1433 DI 10.1093/hmg/4.8.1429 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RM340 UT WOS:A1995RM34000025 PM 7581384 ER PT J AU MAY, M COLLEAUX, L MURGIA, A AYLSWORTH, A NUSSBAUM, R FONTES, M SCHWARTZ, C AF MAY, M COLLEAUX, L MURGIA, A AYLSWORTH, A NUSSBAUM, R FONTES, M SCHWARTZ, C TI MOLECULAR ANALYSIS OF 4 MALES WITH MENTAL-RETARDATION AND DELETIONS OF XQ21 PLACES THE PUTATIVE MR REGION IN XQ21.1 BETWEEN DXS233 AND CHM SO HUMAN MOLECULAR GENETICS LA English DT Note ID X-CHROMOSOME; CHOROIDEREMIA; DEAFNESS; GENE; LOCUS C1 GREENWOOD GENET CTR,GREENWOOD,SC 29646. FAC MED TIMONE,INSERM,U406,MARSEILLE,FRANCE. UNIV PADUA,DEPT PEDIAT,PADUA,ITALY. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CTR BRAIN & DEV,CHAPEL HILL,NC 27599. NCHGR,GENET DIS RES LAB,BETHESDA,MD. FU NEI NIH HHS [R01-EY06566]; NICHD NIH HHS [R01-HD26202] NR 18 TC 20 Z9 20 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 AUG PY 1995 VL 4 IS 8 BP 1465 EP 1466 DI 10.1093/hmg/4.8.1465 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RM340 UT WOS:A1995RM34000032 PM 7581391 ER PT J AU ERICKSON, GF CHUNG, DG SIT, A DEPAOLO, LV SHIMASAKI, S LING, N AF ERICKSON, GF CHUNG, DG SIT, A DEPAOLO, LV SHIMASAKI, S LING, N TI FOLLISTATIN CONCENTRATIONS IN FOLLICULAR-FLUID OF NORMAL AND POLYCYSTIC OVARIES SO HUMAN REPRODUCTION LA English DT Article DE FOLLICULAR FLUID; FOLLISTATIN; OVARY; POLYCYSTIC OVARIAN DISEASE ID ACTIVIN-BINDING PROTEIN; MESSENGER-RIBONUCLEIC-ACID; RAT GRANULOSA-CELLS; HUMAN THECAL CELLS; STIMULATING-HORMONE; PORCINE FOLLISTATIN; ANDROGEN SYNTHESIS; HUMAN SERUM; INHIBIN; EXPRESSION AB Follistatin (FS) is an activin/inhibin binding protein which is believed to act in an autocrine/paracrine manner to regulate growth and differentiation. Although FS has been identified in human follicular fluid, it remains unclear how its concentration changes during selection and atresia, and what the concentrations of FS are in follicles of women with polycystic ovary syndrome (PCOS). Towards this goal, we have measured by radioimmunoassay the concentrations of FS in follicular fluid obtained from dominant and atretic cohort follicles of normal cycling women, preovulatory follicles of in-vitro fertilization (IVF) patients, and small Graafian follicles of patients with PCOS, In all cases, the follicular fluid concentration of FS was much higher (similar to 100-fold) than that reported in serum, The FS concentrations (ng/ml) were 203 +/- 42 (normal dominant), 185 +/- 17 (atretic cohort), 185 +/- 5 (IVF), and 250 +/- 14 (PCOS), There was no statistical difference between these mean values of FS, Further, there were no significant correlations between the follicular fluid concentrations of FS and the concentrations of oestradiol, progesterone, or androstenedione, These results indicate that human Graafian follicles, regardless of whether they are healthy or atretic, normal or PCOS, contain high steady-state concentrations of FS in the micro-environment. Collectively, these data fit with the hypothesis that major increases and decreases in the concentration of FS in the micro-environment may not play a key role in the mechanisms of selection, atresia, and PCOS in women. The possibility of regulation of intrinsic activin and inhibin activity through FS binding is discussed. C1 STANFORD UNIV, SCH MED, STANFORD, CA 94305 USA. NIH, BETHESDA, MD 20892 USA. SCRIPPS RES INST, LA JOLLA, CA 92037 USA. NEUROCRINE BIOSCI INC, LA JOLLA, CA 92037 USA. RP ERICKSON, GF (reprint author), UNIV CALIF SAN DIEGO, DEPT REPROD MED, 9500 GILMAN DR, LA JOLLA, CA 92093 USA. FU NICHD NIH HHS [HD-P50-HD-12303-15, HD-29008] NR 38 TC 22 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD AUG PY 1995 VL 10 IS 8 BP 2120 EP 2124 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA RU037 UT WOS:A1995RU03700037 PM 8567852 ER PT J AU KILPATRICK, KE CARRIER, F SMITH, ML CHEN, CY LEE, AJ RUSNAK, DW KASTAN, MB FORNACE, AJ CHAMPION, BR GILMER, TM SU, JL AF KILPATRICK, KE CARRIER, F SMITH, ML CHEN, CY LEE, AJ RUSNAK, DW KASTAN, MB FORNACE, AJ CHAMPION, BR GILMER, TM SU, JL TI THE PRODUCTION AND CHARACTERIZATION OF MURINE MONOCLONAL-ANTIBODIES TO HUMAN GADD45 RAISED AGAINST A RECOMBINANT PROTEIN SO HYBRIDOMA LA English DT Article ID ELECTROPHORETIC TRANSFER; NITROCELLULOSE SHEETS; POLYACRYLAMIDE GELS; P53 AB The production of two different murine monoclonal antibodies to human Gadd45, a protein that is induced in response to DNA damage, is reported, Antibodies were generated in a SJL mouse using a recombinant form of the human Gadd45 protein. Monoclonal antibody 4TCYA1, which recognizes the denatured form of human Gadd45 in Western blots, was selected based upon the recognition of Gadd45 induced by functional p53 in the human myeloid leukemia cell line, ML-1, A second monoclonal antibody, designated 30T,14, immunoprecipitates native human Gadd45 in lysates produced from RKO cells, a colorectal carcinoma cell line that expresses relatively high basal levels of Gadd45, as well as from cell lysates made from ML-1 cells after exposure to ionizing irradiation (IR), Since 4TCYA1 fails to immunoprecipitate Gadd45, and 30T,14 fails to bind to IR-induced Gadd45 in immunoblotting, these two monoclonal antibodies probably recognize different epitopes. C1 NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21287. GLAXO INC,RES INST,DEPT CELL BIOL,RES TRIANGLE PK,NC 27709. RP KILPATRICK, KE (reprint author), GLAXO INC,RES INST,DEPT CELL PHYSIOL,RES TRIANGLE PK,NC 27709, USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 18 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD AUG PY 1995 VL 14 IS 4 BP 355 EP 359 DI 10.1089/hyb.1995.14.355 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA RN914 UT WOS:A1995RN91400007 PM 8522347 ER PT J AU JOHNSON, CA YAN, YC CARSON, RE MARTINO, RL DAUBEWITHERSPOON, ME AF JOHNSON, CA YAN, YC CARSON, RE MARTINO, RL DAUBEWITHERSPOON, ME TI A SYSTEM FOR THE 3D RECONSTRUCTION OF RETRACTED-SEPTA PET DATA USING THE EM ALGORITHM SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1994 Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) CY OCT 30-NOV 05, 1994 CL NORFOLK, VA SP IEEE ID TOMOGRAPHY; EMISSION AB We have implemented the EM reconstruction algorithm for volume acquisition from current generation retracted-septa PET scanners. Although the software was designed for a GE Advance scanner, it is easily adaptable to other 3D scanners. The reconstruction software was written for an Intel iPSC/860 parallel computer with 128 compute nodes. Running on 32 processors, the algorithm requires approximately 55 minutes per iteration to reconstruct a 128x 128x35 image. No projection data compression schemes or other approximations were used in the implementation. Extensive use of EM system matrix (C-ij) symmetries (including the 8-fold in-plane symmetries, 2-fold axial symmetries, and axial parallelline redundancies) reduces the storage cost by a factor of 188. The parallel algorithm operates on distributed projection data which are decomposed by base-symmetry angles. Symmetry operators copy and index the C-ij chord to the form required for the particular symmetry. The use of asynchronous reads, lookup tables, and optimized image indexing improves computational performance. C1 NIH,CTR CLIN,DEPT PET,BETHESDA,MD 20892. RP JOHNSON, CA (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 11 TC 57 Z9 58 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD AUG PY 1995 VL 42 IS 4 BP 1223 EP 1227 DI 10.1109/23.467875 PN 1 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA RP819 UT WOS:A1995RP81900179 ER PT J AU APASOV, S KOSHIBA, M REDEGELD, F SITKOVSKY, MV AF APASOV, S KOSHIBA, M REDEGELD, F SITKOVSKY, MV TI ROLE OF EXTRACELLULAR ATP AND P1 AND P2 CLASSES OF PURINERGIC RECEPTORS IN T-CELL DEVELOPMENT AND CYTOTOXIC T-LYMPHOCYTE EFFECTOR FUNCTIONS SO IMMUNOLOGICAL REVIEWS LA English DT Review ID DEPENDENT PROTEIN-KINASE; MEDIATED CYTOTOXICITY; ADENOSINE-DEAMINASE; ACTIVATION; LYSIS; THYMOCYTES; MODULATION; ANTIGEN RP APASOV, S (reprint author), NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N-311,BETHESDA,MD 20892, USA. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 40 TC 87 Z9 89 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 1995 VL 146 BP 5 EP 19 DI 10.1111/j.1600-065X.1995.tb00680.x PG 15 WC Immunology SC Immunology GA RP800 UT WOS:A1995RP80000001 PM 7493760 ER PT J AU RAZIN, E PECHT, I RIVERA, J AF RAZIN, E PECHT, I RIVERA, J TI SIGNAL-TRANSDUCTION IN THE ACTIVATION OF MAST-CELLS AND BASOPHILS SO IMMUNOLOGY TODAY LA English DT Article AB Mast cells are gaining recognition as participants in many inflammatory responses in addition to their well-documented role in anaphylaxis. However, the biochemical pathways underlying the ability of extracellular stimuli to activate intracellular events still require resolution. This report, from a recent workshop*, summarizes some of the advances in this field. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NIAMS,CHEM IMMUNOL SECT,BETHESDA,MD 20892. RP RAZIN, E (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT BIOCHEM,IL-91120 JERUSALEM,ISRAEL. NR 0 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD AUG PY 1995 VL 16 IS 8 BP 370 EP 373 DI 10.1016/0167-5699(95)80003-4 PG 4 WC Immunology SC Immunology GA RM704 UT WOS:A1995RM70400003 PM 7546191 ER PT J AU TING, CC WANG, J HARGROVE, ME AF TING, CC WANG, J HARGROVE, ME TI REVERSAL OF MULTIPLE-SITE TUMOR CELL-INDUCED IMMUNOSUPPRESSION BY SPECIFIC CYTOKINES AND PHARMACOLOGICAL AGENTS SO IMMUNOPHARMACOLOGY LA English DT Article DE TUMOR; IMMUNOSUPPRESSION; REVERSAL OF SUPPRESSION ID ACTIVATED KILLER-CELLS; TOXIC LYMPHOCYTES-T; PROTEIN-KINASE; SIGNAL TRANSDUCTION; BEARING MICE; MACROPHAGE; MECHANISM; ANTIBODY; CANCER; EL-4 AB The present study explores a model for tumor cell-induced immunosuppression and reversal of suppression by cytokines and other pharmacological agents. To simulate tumor-cell-induced suppression, a panel of suppressor agents which included CsA (cyclosporin A), SSP (staurosporine), BSO (L-buthionine-[S,R]-sulfoximine) and PMA, and a panel of anti-suppressor agents which included IL-2, IL-4, GSH (glutathione) and amiloride, were tested. These suppressor/anti-suppressor agents acted differently on four specific sites of the immune arm that affected the alpha CD3-induced T cell proliferative and cytotoxic responses. They included (1) IL-2 production, (2) PKC-regulated cytolytic granule production, (3) GSH-regulated maturation of functional granules, and (4) granule exocytosis. When a single suppressor agent was used, all the suppressor agents tested in this study inhibited the generation of alpha CD3-induced activated killer cells (CD3-AK), whereas alpha CD3-induced proliferation was inhibited by CsA, BSO, and EL-4 tumor cells. Except for EL-4, suppression induced by a single suppressor agent could be corrected by an appropriate single anti-suppressor agent. Multiple suppressor agents induced profound suppression of CD3-AK response. In most cases, multiple anti-suppressor agents were required to correct the immune defects induced by multiple suppressor agents. Finally, EL-4 tumor-cell-induced immunosuppression could not be corrected by any single anti-suppressor agent tested, but a combination of IL-4, GSH and amiloride fully restored the CDS-AK response. These results suggest that tumor cells may induce multiple immune defects that require multiple anti-suppressor agents for correcting the defects to restore the host immunocompetence. RP TING, CC (reprint author), NCI,DIV CELL BIOL DIAG & CTR,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 40 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD AUG PY 1995 VL 30 IS 2 BP 119 EP 130 DI 10.1016/0162-3109(95)00013-J PG 12 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA RR794 UT WOS:A1995RR79400002 PM 8530253 ER PT J AU GUPTA, RK EGAN, W BRYLA, DA ROBBINS, JB SZU, SC AF GUPTA, RK EGAN, W BRYLA, DA ROBBINS, JB SZU, SC TI COMPARATIVE IMMUNOGENICITY OF CONJUGATES COMPOSED OF ESCHERICHIA-COLI O111 O-SPECIFIC POLYSACCHARIDE, PREPARED BY TREATMENT WITH ACETIC-ACID OR HYDRAZINE, BOUND TO TETANUS TOXOID BY 2 SYNTHETIC SCHEMES SO INFECTION AND IMMUNITY LA English DT Article ID SHIGELLA-DYSENTERIAE TYPE-1; INFLUENZAE TYPE-B; LIPID-A CORE; CHAIN-LENGTH; LIPOPOLYSACCHARIDE; ANTIGEN; ANTIBODIES; OLIGOSACCHARIDE; IMMUNIZATION; VACCINES AB Escherichia coli O111, of various H types and virulence factors, causes enteritis throughout the world, especially in young children. This O type is found rarely in healthy individuals. Serum antibodies to the O-specific polysaccharide of O111 lipopolysaccharide (LPS) protect mice and dogs against infection with this E. coli serotype. The O111 O-specific polysaccharide is composed of a pentasaccharide repeat unit with two colitoses bound to the C-3 and C-6 of glucose in a trisaccharide backbone; this structure is identical to that of Salmonella adelaide (O35), another enteric pathogen. Nonpyrogenic O111 O-specific polysaccharide was prepared by treatment of its LPS with acetic acid (O-SP) or the organic base hydrazine (DeA-LPS). The O-SP had a reduced concentration of colitose. These products were derivatized with adipic acid dihydrazide (ADH) or thiolated with N-succinimidyl-3(2-pyridyldithio) propionate (SPDP). The four derivatives were covalently bound to tetanus toroid (TT) by carbodiimide-mediated condensation or with SPDP to form conjugates. Immunization of BALB/c and general-purpose mice by a clinically acceptable route showed that DeA-LPST-TTADH, of the four conjugates, elicited the highest level of LPS antibodies. Possible reasons to explain this differential immunogenicity between the four conjugates are discussed. C1 NICHHD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 52 TC 27 Z9 29 U1 1 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 AUG PY 1995 VL 63 IS 8 BP 2805 EP 2810 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000001 PM 7542631 ER PT J AU MUCCI, D FORRISTAL, J STRICKLAND, D MORRIS, R FITZGERALD, D SAELINGER, CB AF MUCCI, D FORRISTAL, J STRICKLAND, D MORRIS, R FITZGERALD, D SAELINGER, CB TI LEVEL OF RECEPTOR-ASSOCIATED PROTEIN MODERATES CELLULAR-SUSCEPTIBILITY TO PSEUDOMONAS EXOTOXIN-A SO INFECTION AND IMMUNITY LA English DT Article ID NEPHRITIS ANTIGENIC COMPLEX; LIPOPROTEIN RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; AERUGINOSA EXOTOXIN; LDL-RECEPTOR; PLASMINOGEN-ACTIVATOR; CHYLOMICRON REMNANTS; HIGH-AFFINITY; BINDING; TOXIN AB Pseudomonas exotoxin A (PE) enters mammalian cells via a receptor-mediated endocytic pathway. The initial step in this pathway is binding to the multiligand receptor termed the alpha(2)-macroglobulin receptor/low-density lipoprotein receptor-related protein (LRP). Binding of toxin, and of the many other ligands that bind to LRP, is blocked by the addition of a 39-kDa receptor-associated protein (RAP), sere we show that approximately 40% of the cell-associated LRP is on the surface of toxin-sensitive mouse LM fibroblasts and thus accessible for toxin internalization. The remainder is located intracellularly, primarily in the Golgi region. Mammalian cells exhibit a wide range of sensitivity to PE. To investigate possible reasons for this, we examined the expression levels of both LRP and RAP. Results from a variety of cell lines indicated that there was a positive correlation between LRP expression and toxin sensitivity. In the absence of LRP, cells were as much as 200-fold more resistant to PE compared with sensitive cells. A second group of resistant cells expressed LRP but had a high level of RAP. Thus, a toxin-resistant phenotype would be expected when cells expressed either low levels of LRP or high levels of LRP in the presence of high levels of RAP. We hypothesize that RAP has a pivotal role in moderating cellular susceptibility to PE. C1 UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET,CINCINNATI,OH 45267. UNIV CINCINNATI,COLL MED,DEPT CELL BIOL,CINCINNATI,OH 45267. AMER RED CROSS,BIOCHEM LAB,ROCKVILLE,MD 20855. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL50787]; NIAID NIH HHS [AI-17529]; NIGMS NIH HHS [GM42581] NR 63 TC 13 Z9 14 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 AUG PY 1995 VL 63 IS 8 BP 2912 EP 2918 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RK640 UT WOS:A1995RK64000017 PM 7622212 ER PT J AU GIESE, T DAVIDSON, WF AF GIESE, T DAVIDSON, WF TI THE ACCUMULATION OF B220(+) CD4(-) CD8(-) (DN) T-CELLS IN C3H-LPR/LPR MICE IS NOT ACCELERATED BY THE STIMULATION OF CD8(+) T-CELLS OR B220(+) DN T-CELLS WITH STAPHYLOCOCCAL-ENTEROTOXIN-B AND OCCURS INDEPENDENTLY OF V(BETA)8(+) T-CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE DELETION; FAS; GLD; LIGAND; IPR; SUPERANTIGEN; TOLERANCE ID LPR MICE; LPR/LPR MICE; MONOCLONAL-ANTIBODY; MRL/LPR MICE; FAS ANTIGEN; RECEPTOR; EXPRESSION; GLD; GENE; APOPTOSIS AB Mice homozygous for Ipr or gld develop lymphoproliferative disease characterized by the progressive accumulation of functionally impaired B220(+) double-negative (DN)T cells and primed CD4(+) and CD8(+) T cells. The mechanisms leading to the accumulation of these T cell subsets are poorly understood but are clearly dependent on lack of expression of Fas in Ipr mice and expression of defective Fast in gld mice. A role for V(beta)8(+) T cells also has been reported. Recently, a variety of experimental approaches revealed that the majority of B220(+) DN T cells are derived from MHC class I-selected CD8(+) precursors. Here we used the potent mitogen, staphylococcal enterotoxin 8 (SEB): (i) to examine the effects of defective Fas-FasL expression on the deletion of peripheral V(beta)8(+) T cells in 6- to 8- and 20-week old C3H-Ipr and -gld mice, (ii) to determine the immunocompetence of B220(+) DN T cells in vivo, and (iii) to determine if activated V(beta)8(+) CD8(+) T cells can differentiate into B220(+) DN T cells. The role of V(beta)8(+) T cells in the accumulation of B220(+) DN T cells also was reinvestigated. These studies showed that deletion pathways independent of Fas-FasL expression function in young Ipr and gld mice and delete CD4(+) T cells more efficiently than CD8(+) T cells. As the mice age, these alternative pathways become less effective and this may explain the progressive accumulation of memory T cells. No abnormalities in tolerance induction were observed in young or diseased mice. Stimulation of +/+, Ipr and gld V(beta)8(+) CD8(+) T cells induced the expression of B220, B220 levels were maximal 2 days after SEE and were undetectable 5 days later, suggesting that B220 is a transiently expressed activation marker on CD8(+) T cells. Neither the B220(+) V(beta)8(+) CD8(+) T cells nor other V(beta)8(+) T cell populations converted with detectable frequency into B220(+) DN T cells after single or multiple doses of SEB. B220(+) DN T cells, which are functionally anergic in vitro, did not proliferate or undergo deletion after SEB stimulation indicating that these cells also are functionally impaired in vivo. In contrast to previous reports, chronic elimination of V(beta)8(+) T cells had no effect on the accumulation of B220(+) DN T cells. These data suggest, first, that the accumulation of B220(+) DN T cells is unlikely to occur solely by antigen-induced proliferation of B220(+) DN T cells but also may be dependent on the continuous conversion of putative CD8(+) MHC class I selected precursors into B220(+) DN T cells. Second, strongly activated CD8(+) T cells that avoid deletion in the periphery are an unlikely source of B220(+) DN T cells. C1 NCI,GENET LAB,BETHESDA,MD 20892. NR 47 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 1995 VL 7 IS 8 BP 1213 EP 1223 DI 10.1093/intimm/7.8.1213 PG 11 WC Immunology SC Immunology GA RP590 UT WOS:A1995RP59000006 PM 7495728 ER PT J AU BURGER, RA ALVAREZSALAS, LM WILCZYNSKI, SP MONK, BJ DIPAOLO, JA AF BURGER, RA ALVAREZSALAS, LM WILCZYNSKI, SP MONK, BJ DIPAOLO, JA TI POLYMORPHISM OF THE HPV-16 E6 GENE OF CERVICAL-CARCINOMA SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE HPV-16; E6 GENE; CERVICAL CARCINOMA ID HUMAN PAPILLOMAVIRUS TYPE-16; SEQUENCE VARIATION; P53; DNA; TRANSACTIVATION; DEGRADATION; VARIANTS; SPREAD AB Polymorphism of the human papillomavirus type 16 (HPV-16) genome has been reported to occur within the noncoding regulatory long control region (LCR) and in the E7 and L1 genes. The current study focuses on the HPV-16 E6 oncogene which interacts with the antioncogenic regulator p53. Seventy-eight HPV-16-positive DNA samples derived from cervical carcinomas were screened for the presence of polymorphism in the HPV-16 E6 gene by polymerase chain reaction (PCR) linked single stranded conformational polymorphism (SSCP) analysis. Nine DNA samples had heterozygous mutations within the same region of the E6 gene 3' terminus; T to C transitions at HPV-16 position 511 (silent) and one of the nine also had a 513 mutation (Met to Thr). These mutations correlated with the clinical aggressiveness of the tumor, suggesting that the presence of these mutations may be due to genomic instability of advanced cervical carcinoma. C1 NCI,BIOL LAB,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,DEPT PATHOL,DUARTE,CA 91010. UNIV CALIF IRVINE,UCI MED CTR,CTR CLIN CANC,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,ORANGE,CA 92717. NR 28 TC 11 Z9 11 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 AUG PY 1995 VL 7 IS 2 BP 261 EP 266 PG 6 WC Oncology SC Oncology GA RK353 UT WOS:A1995RK35300008 PM 21552834 ER PT J AU POPESCU, NC ZIMONJIC, DB SIMPSON, S DIPAOLO, JA AF POPESCU, NC ZIMONJIC, DB SIMPSON, S DIPAOLO, JA TI CUMULATIVE GENE AND CHROMOSOME ALTERATIONS ASSOCIATED WITH IN-VITRO NEOPLASTIC TRANSFORMATION OF HUMAN CERVICAL CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CERVICAL CANCER; HUMAN PAPILLOMAVIRUS; PROTOONCOGENE; TUMOR SUPPRESSOR GENE; CHROMOSOME CHANGES ID HUMAN PAPILLOMAVIRUS-16 DNA; C-MYC ONCOGENE; UTERINE CERVIX; RETINOBLASTOMA PROTEIN; MOLECULAR ALTERATIONS; HUMAN KERATINOCYTES; EPITHELIAL-CELLS; TOPOISOMERASE-II; HELA-CELLS; EXPRESSION AB The development of cancer is a multistep process requiring cumulative genetic alterations. An in vit ro model utilizing human cervical cells and papillomaviruses (HPV) that mimics human cervical cancer has been developed. Chromosome and gene alterations associated with distinctive stages of neoplastic transformation were demonstrated with an exocervical cell line obtained after sequential transfection with recombinant HPV-16 DNA and v-Ha-ras oncogene. Acquisition of immortality after HPV-16 transfection was associated with aneuploidy, structural changes of chromosomes 8, 10, 17, 19, 20, and 21, as well as proto-oncogene alterations. HPV-16 DNA was localized to two sites on chromosome 21, with one site at 21q22.2-22.3 near the ets-2 proto-oncogene. Ets-2 as well as c-myc gene mRNA levels were elevated in HPV immortal cells compared to primary nontransfected exocervical strains. Although the HPV-immortalized cells had several features characteristic of malignant cells, they lacked tumorigenic potential. Tumorigenicity occurred after transfection with v-Ha-ras oncogene, which was found stably integrated on chromosome 12 at the telomeric band q24.3. The tumorigenic line had additional clonal chromosomal abnormalities; consisting of multiple deletions involving regions of chromosomes 1p/q, 3p, 9q, loss of one copy of chromosome 11, and a complex rearrangement of chromosomes 8 and 13 as shown by in situ suppression hybridization with whole chromosome probes. Loss of tumor suppressor genes on deleted regions may have contributed to the acquisition of tumorigenicity. The genetic changes observed in these cells parallel those found in cervical carcinomas, demonstrating the validity of the in vitro model for studying the multistep progression resulting in cervical carcinoma. RP POPESCU, NC (reprint author), NCI,BIOL LAB,BLDG 37,ROOM 2A15,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 60 TC 11 Z9 12 U1 1 U2 2 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 AUG PY 1995 VL 7 IS 2 BP 279 EP 285 PG 7 WC Oncology SC Oncology GA RK353 UT WOS:A1995RK35300011 PM 21552837 ER PT J AU BERNSTEIN, EF PASS, HA GLASS, J DELUCA, AM COOK, S FISHER, J COOK, JA AF BERNSTEIN, EF PASS, HA GLASS, J DELUCA, AM COOK, S FISHER, J COOK, JA TI MODULATION OF CISPLATIN TOXICITY BY GLUTATHIONE SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE GLUTATHIONE; KIDNEY; TUMOR; TOXICITY; PROTECTION; CISPLATIN ID MELPHALAN CYTO-TOXICITY; CANCER CELL-LINE; REDUCED GLUTATHIONE; BUTHIONINE SULFOXIMINE; OVARIAN-CANCER; DEPLETION; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; POTENTIATION; METABOLISM AB Organ toxicity is the major limiting factor associated with chemotherapeutic treatment of malignancy. By raising the toxicity threshold of the organ to the detrimental effects of chemotherapeutic agents, larger and possibly curative doses may be administered without unacceptable side effects. Glutathione (GSH), a major nonprotein cellular thiol, participates in numerous cellular functions, including detoxification of chemotherapeutic agents. Previously, GSH was shown to protect against cisplatin-induced lethal toxicity. We find that in non-tumor bearing animals GSH injections (500 mg/kg body weight) prior to and after a single cisplatin injection (16 mg/kg) provided significant protection against the lethal effects of this drug (90% survival for GSH+cisplatin versus 35% for cisplatin alone). In addition, when GSH was given concurrently with the cisplatin, renal toxicity was markedly reduced as assessed by renal tubular dilation, tubular sloughing, and lumenal casts. When GSH was given with cisplatin no significant differences in the number of tumor cures was observed over cisplatin treatment alone; however, a small but statistically significant increase in tumor size was observed for cisplatin+GSH treated animals. Our results suggest that GSH may protect normal as well as malignant tissue and that further studies should be designed to determine a GSH dose and schedule regimen to be used with higher cisplatin dose schedules. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,PHILADELPHIA,PA 19107. NR 38 TC 7 Z9 7 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1995 VL 7 IS 2 BP 353 EP 358 PG 6 WC Oncology SC Oncology GA RK353 UT WOS:A1995RK35300021 PM 21552847 ER PT J AU DONG, ZG WATTS, RG SUN, Y ZHAN, SN COLBURN, NH AF DONG, ZG WATTS, RG SUN, Y ZHAN, SN COLBURN, NH TI PROGRESSIVE ELEVATION OF AP-1 ACTIVITY DURING PRENEOPLASTIC-TO-NEOPLASTIC PROGRESSION AS MODELED IN MOUSE JB6 CELL VARIANTS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE AP-1; TUMOR PROGRESSION; TUMOR PHENOTYPE EXPRESSION ID TUMOR PROMOTERS; C-JUN; RESISTANT; GENES; CARCINOGENESIS; MECHANISMS; EXPRESSION; ACID AB The JB6 mouse epidermal cell system has been used extensively as an in vitro model for the study of tumor promotion and progression. The present study was directed to assessing the role of basal AP-1 activity in JB6 variants which represent preneoplastic to neoplastic progression and to addressing whether AP-1 activity is required for maintenance of the tumor phenotype. Constitutively higher AP-1 activity was found in tumorigenic JB6 RT101 cells than in later or earlier preneoplastic P+ or P- cells. Levels of c-jun mRNA and protein correlated with progression stage. Enhancement of AP-1 activity by TPA increased the formation of anchorage independent colonies by tumorigenic RT101 cells. Inhibition of AP-1 activity by retinoic acid or fluocinolone acetonide inhibited expression of tumor phenotype as measured by AI growth. These data together with our previous results suggest that in the JB6 model (i) basal levels of Jun and AP-1 appear to be important for preneoplastic-to-neoplastic progression; (ii) induced AP-1 appears to be required for further progression by tumor cells; (iii) constitutively elevated AP-I activity may be important for the expression of transformed phenotype; (iv) inhibition of AP-1 activity by RA or FA is not a general suppression of transcription but is gene-specific; and (v) even though both inhibition of AP-1 activity and activation of RARE-dependent or GRE-dependent gene transcription correlate with inhibition of AI growth in RT101 cells by RA or FA, transactivation of RARE or GRE might better correlate with the inhibition of AI growth than the inhibition of AP-1 activity in RT101 cells. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. RP DONG, ZG (reprint author), UNIV MINNESOTA,HORMEL INST,801 16TH AVE NE,AUSTIN,MN 55912, USA. NR 20 TC 60 Z9 62 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1995 VL 7 IS 2 BP 359 EP 364 PG 6 WC Oncology SC Oncology GA RK353 UT WOS:A1995RK35300022 PM 21552848 ER PT J AU WESTERGAARD, GC GREENE, JA BABITZ, MA SUOMI, SJ AF WESTERGAARD, GC GREENE, JA BABITZ, MA SUOMI, SJ TI PESTLE USE AND MODIFICATION BY TUFTED CAPUCHINS (CEBUS-APELLA) SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE CAPUCHIN; CEBUS; CHIMPANZEE; MORTAR AND PESTLE; PAN; TOOL-USE ID TOOL USE; SENSORIMOTOR INTELLIGENCE; MONKEYS; APES AB We examined the use and modification of pestles by tufted capuchins (Cebus apella). In each of two experiments we presented 18 subjects with an apparatus that held sugarcane along with materials that the animals could use as tools. In Experiment 1 we presented the subjects with sticks, and in Experiment 2 we presented them with sticks, stones, paper towels, and food biscuits. Seven subjects used sticks as pestles to break down fiber to and squeeze sap from sugarcane in Experiment 1. Five of them modified sticks for this purpose. In Experiment 2, 10 animals used pestles and sponges, combined tools, and used pestles to mix together different kinds of food. These results provide further evidence of functional convergence for the use and modification of tools by Cebus and Pan and are consistent with the view that extractive foraging is associated with the tool-using and toolmaking behavior of primates. C1 HARVARD UNIV,DEPT BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,DEPT ANTHROPOL,CAMBRIDGE,MA 02138. UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POB 529,POOLESVILLE,MD 20837, USA. NR 20 TC 12 Z9 12 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD AUG PY 1995 VL 16 IS 4 BP 643 EP 651 PG 9 WC Zoology SC Zoology GA RP893 UT WOS:A1995RP89300005 ER PT J AU ROBISON, WG AF ROBISON, WG TI DIABETIC-RETINOPATHY - GALACTOSE-FED RAT MODEL SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter ID ALDOSE REDUCTASE INHIBITOR; RETINAL CAPILLARIES; PREVENTION; TOLRESTAT; SORBINIL; CATARACT RP ROBISON, WG (reprint author), NEI,BETHESDA,MD 20892, USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 1995 VL 36 IS 9 BP A4 EP & PG 0 WC Ophthalmology SC Ophthalmology GA RN213 UT WOS:A1995RN21300001 PM 7635650 ER PT J AU PRAS, M PRAS, E KASTNER, D AF PRAS, M PRAS, E KASTNER, D TI THE ORIGIN OF THE FMF GENE SO ISRAEL JOURNAL OF MEDICAL SCIENCES LA English DT Editorial Material DE FAMILIAL MEDITERRANEAN FEVER; SEPHARDIC JEWS; GENETICS C1 NIH,BETHESDA,MD 20892. RP PRAS, M (reprint author), CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. NR 8 TC 2 Z9 2 U1 0 U2 0 PU ISRAEL JOURNAL MED SCIENCES PI JERUSALEM PA 2 ETZEL ST, FRENCH HILL, JERUSALEM 97853, ISRAEL SN 0021-2180 J9 ISRAEL J MED SCI JI Isr. J. Med. Sci. PD AUG PY 1995 VL 31 IS 8 BP 503 EP 504 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RR523 UT WOS:A1995RR52300010 PM 7635702 ER PT J AU ZUBER, M HOOVER, TA COURT, DL AF ZUBER, M HOOVER, TA COURT, DL TI ANALYSIS OF A COXIELLA-BURNETII GENE-PRODUCT THAT ACTIVATES CAPSULE SYNTHESIS IN ESCHERICHIA-COLI - REQUIREMENT FOR THE HEAT-SHOCK CHAPERONE DNAK AND THE 2-COMPONENT REGULATOR RCSC SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; POLYSACCHARIDE SYNTHESIS; PLASMID VECTOR; RNC OPERON; K-12; IDENTIFICATION; EXPRESSION; CLONING; PROTEINS; MUTATION AB A 1.2-kb EcoRI genomic DNA fragment of Coxiella burnetii, when cloned onto a multicopy plasmid, was found to induce capsule synthesis (mucoidy) in Escherichia coli. Nucleotide sequence analysis revealed the presence of an open reading frame that could encode a protein of 270 amino acids. Insertion of a tet cassette into a unique NruI restriction site resulted in the loss of induction of mucoidy. Because of its ability to induce mucoidy, we designated this gene mucZ. Computer search for homologies to mucZ revealed 42% identity to an open reading frame located at 1 min of the E. coli chromosome. Interestingly, the C-terminal amino acid residues of MucZ share significant homology with the J domain of the DnaJ protein and its homologs, suggesting potential interactions between MucZ and components of the DnaK-chaperone machinery. Results presented in this paper suggest that E. coli requires DnaK-chaperone machinery for Lon-RcsA-mediated induction of capsule synthesis, as noticed first by S. Gottesman (personal communication). The induction caused by MucZ is independent of Lon-RcsA and is mediated through the two-component regulators RcsC and RcsB. DnaK and GrpE but not DnaJ are also required for the RcsB-mediated MucZ induction, and we propose that MucZ is a DnaJ-like chaperone protein that might be required for the formation of an active RcsA-RcsB complex and for the RcsC dependent phosphorylation of RcsB. Discussions are presented that suggest three different roles for alternative forms of the DnaK-chaperone machinery in capsule production. C1 USA,MED RES INST INFECT DIS,DIV BACTERIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. RP ZUBER, M (reprint author), USA,MED RES INST INFECT DIS,DIV TOXICOL,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-46000] NR 41 TC 36 Z9 38 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 1995 VL 177 IS 15 BP 4238 EP 4244 PG 7 WC Microbiology SC Microbiology GA RL828 UT WOS:A1995RL82800006 PM 7635811 ER PT J AU DEERFIELD, DW PEDERSEN, LG AF DEERFIELD, DW PEDERSEN, LG TI THE FIRST SOLVATION SHELL OF MAGNESIUM AND CALCIUM-IONS IN A MODEL NUCLEIC-ACID ENVIRONMENT - AN AB-INITIO STUDY SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID REPRESSOR OPERATOR COMPLEX; CRYSTAL-STRUCTURE; MOLECULAR MECHANICS; CATION BINDING; PHOSPHATE; QUANTUM; NA+; RECOGNITION; RESOLUTION; ALGORITHM AB The interaction of organophosphate anions with divalent metal ions is central to many biological catalytic events. While experimental structural studies can give insight into the likely geometries that can be adopted, quantum mechanics allows for a more complete exploration of the competing forms. Ab initio quantum mechanical calculations have been performed on a series of complexes comprised of dimethyl phosphate, a divalent metal ion (either Mg(II) or Ca(II)) and water of hydration. An additional series of complexes were studied that included a Cl(I) ion to provide for charge neutrality. The most stable orientation of the hydrated metal ion complexed with the phosphate anion occurs when the metal ion is in a unidentate, rather than bidentate, orientation. The question of whether the divalent metal ion is located in the phosphinyl (-PO2--) plane depends on the identity of the divalent metal ion and on the charge state of the complex. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. RP DEERFIELD, DW (reprint author), PITTSBURGH SUPERCOMP CTR,4400 5TH AVE,PITTSBURGH,PA 15213, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NCRR NIH HHS [1 P41 RR06009]; NHLBI NIH HHS [HL-26309, HL-27995] NR 41 TC 10 Z9 10 U1 0 U2 1 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD AUG PY 1995 VL 13 IS 1 BP 167 EP 180 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RU653 UT WOS:A1995RU65300013 PM 8527028 ER PT J AU BERNIER, SM NAKATA, K YAMADA, Y AF BERNIER, SM NAKATA, K YAMADA, Y TI ANNEXIN-V MESSENGER-RNA IS REGULATED DURING CHONDROCYTIC DIFFERENTIATION IN-VITRO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S232 EP S232 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400373 ER PT J AU FOWLER, S GALLAGHER, JC DAWSONHUGHES, B DALSKY, G SHERMAN, S AF FOWLER, S GALLAGHER, JC DAWSONHUGHES, B DALSKY, G SHERMAN, S TI A COMPARISON OF DIFFERENT INTERVENTIONS ON FEMORAL-NECK BONE LOSS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HENRY FORD HOSP,HLTH SCI CTR,DETROIT,MI 48202. CREIGHTON UNIV,OMAHA,NE 68178. TUFTS UNIV,BOSTON,MA 02111. UNIV CONNECTICUT,FARMINGTON,CT 06032. NIA,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S458 EP S458 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401277 ER PT J AU FREEMAN, S KING, JC VIEIRA, NE WOODHOUSE, L YERGEY, AL AF FREEMAN, S KING, JC VIEIRA, NE WOODHOUSE, L YERGEY, AL TI INTRODUCTION OF A LIFETIME MEASURABLE DOSE OF CA-41 INTO BONE AND MEASUREMENT OF TURNOVER SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94550. UNIV CALIF BERKELEY,DEPT NUTR SCI,BERKELEY,CA 94720. NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S476 EP S476 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401349 ER PT J AU GRZESIK, WJ MAIGRZESIK, Y IVANOV, B ROBEY, PG AF GRZESIK, WJ MAIGRZESIK, Y IVANOV, B ROBEY, PG TI INTERACTION OF HUMAN BONE-CELLS WITH SYNTHETIC PEPTIDES DERIVED FROM BONE SIALOPROTEIN DIFFERING IN THEIR SPATIAL CONFORMATION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIDDK,DIABET BRANCH,BETHESDA,MD. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S319 EP S319 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400723 ER PT J AU JEROME, CP SASS, DA BENNETT, A BOWMAN, AR LEROITH, D EPSTEIN, S AF JEROME, CP SASS, DA BENNETT, A BOWMAN, AR LEROITH, D EPSTEIN, S TI EFFECTS OF SHORT-TERM TREATMENT WITH GROWTH-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I ON VERTEBRAL BONE IN AGED MONKEYS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. ALBERT EINSTEIN MED CTR,NO DIV,PHILADELPHIA,PA 19141. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S254 EP S254 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400463 ER PT J AU KIEL, DP ROUBENOFF, R HANNAN, MT HARRIS, TB FELSON, DT AF KIEL, DP ROUBENOFF, R HANNAN, MT HARRIS, TB FELSON, DT TI THE ASSOCIATION OF PERIPHERAL WBC DERIVED INTERLEUKIN-1 (IL-1) TUMOR-NECROSIS-FACTOR (TNF), INTERLEUKIN-6 (IL-6) WITH BONE-MINERAL DENSITY (BMD) IN A LARGE COHORT STUDY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,HEBREW REHABIL CTR AGED,BOSTON,MA 02118. USDA,HUMAN NUTR RES CTR,BOSTON,MA 02118. TUFTS UNIV,BOSTON,MA 02111. BOSTON UNIV,CTR ARTHRITIS,BOSTON,MA 02118. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S466 EP S466 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401310 ER PT J AU KREBSBACH, PH KUZNETSOV, SA ROWE, DW ROBEY, PG AF KREBSBACH, PH KUZNETSOV, SA ROWE, DW ROBEY, PG TI MARROW STROMAL FIBROBLASTS ACTIVATE A BONE SPECIFIC COLLAGEN-1 CONSTRUCT AND FORM BONE IN-VIVO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S205 EP S205 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400268 ER PT J AU KUZNETSOV, SA ROBEY, PG AF KUZNETSOV, SA ROBEY, PG TI BONE-MARROW CFU-FS (COLONY-FORMING-UNITS FIBROBLAST) REQUIRE BOTH BFGF AND PDGF FOR INITIAL PROLIFERATION IN-VITRO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S205 EP S205 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400266 ER PT J AU LIANG, CT BARNES, J AF LIANG, CT BARNES, J TI RENAL EXPRESSION OF OSTEOPONTIN AND ALKALINE-PHOSPHATASE CORRELATES WITH RENAL-FUNCTION IN OLD AND PARATHYROID HORMONE-TREATED YOUNG-RATS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S379 EP S379 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400959 ER PT J AU LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL AF LOOKER, AC JOHNSTON, CC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP LINDSAY, RL TI DEFINING LOW FEMUR BONE-DENSITY LEVELS IN MEN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NCHS,HYATTSVILLE,MD 20782. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NIA,BETHESDA,MD 20892. US FDA,WASHINGTON,DC 20204. INDIANA UNIV,INDIANAPOLIS,IN 46223. HELEN HAYES HOSP,W HAVERSTRAW,NY 10993. NIAMS,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S468 EP S468 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401318 ER PT J AU MAHMOODIAN, F PETERKOFSKY, B AF MAHMOODIAN, F PETERKOFSKY, B TI REGULATION OF BONE ALKALINE-PHOSPHATASE DURING VITAMIN-C-DEFICIENCY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S239 EP S239 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400401 ER PT J AU OCONNOR, KG HARMAN, SM TOBIN, JD ROY, TA BELLANTONI, MF BLACKMAN, MR AF OCONNOR, KG HARMAN, SM TOBIN, JD ROY, TA BELLANTONI, MF BLACKMAN, MR TI INTERACTIONS AMONG GH, IGF-I, OSTEOCALCIN AND BODY-FAT AS PREDICTORS OF BONE-MINERAL DENSITY IN HEALTHY ELDERLY PEOPLE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S180 EP S180 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400168 ER PT J AU RIMINUCCI, M CORSI, A FISHER, LW ROBEY, P BIANCO, P AF RIMINUCCI, M CORSI, A FISHER, LW ROBEY, P BIANCO, P TI SECRETION OF BONE SIALOPROTEIN IS REGULATED IN PRIMARY RAT OSTEOBLAST-LIKE CELLS AND DEREGULATED IN UMR-106-01-BSP CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. UNIV LAQUILA,I-67100 LAQUILA,ITALY. UNIV ROME,I-00100 ROME,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S320 EP S320 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400724 ER PT J AU SEBAG, M WHITE, J RHIM, J KREMER, R AF SEBAG, M WHITE, J RHIM, J KREMER, R TI DISRUPTION OF VDR/RXR HETERODIMER FORMATION IN A VITAMIN-D-RESISTANT RAS-TRANSFORMED KERATINOCYTE CELL-LINE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MCGILL UNIV,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3A 1A1,CANADA. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S167 EP S167 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400115 ER PT J AU SHERMAN, SS NEER, R GREENDALE, G SOWERS, MF GOLD, E MATTHEWS, K MCKINLAY, S MIDGLEY, AR POWELL, L WEISS, G AF SHERMAN, SS NEER, R GREENDALE, G SOWERS, MF GOLD, E MATTHEWS, K MCKINLAY, S MIDGLEY, AR POWELL, L WEISS, G TI SWAN - A MULTIETHNIC STUDY OF THE PERIMENOPAUSAL TRANSITION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S266 EP S266 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400508 ER PT J AU STUBBS, JT EANES, ED FISHER, LW AF STUBBS, JT EANES, ED FISHER, LW TI THE USE OF NATIVE AND RECOMBINANT FRAGMENTS TO DELINEATE NON-RGD CELL ATTACHMENT DOMAINS AND MINERAL-BINDING DOMAINS OF BONE SIALOPROTEIN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRAIN,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S432 EP S432 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48401174 ER PT J AU VANDERPUIJM, G IVANOV, B ROBEY, F ROBEY, PG PAPAPOULOS, S LOWIK, C AF VANDERPUIJM, G IVANOV, B ROBEY, F ROBEY, PG PAPAPOULOS, S LOWIK, C TI BONE-SIALOPROTEIN PEPTIDES ARE POTENT INHIBITORS OF BREAST-CANCER CELL-ADHESION TO BONE IN-VITRO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 LEIDEN UNIV HOSP,DEPT ENDOCRINOL,2333 AA LEIDEN,NETHERLANDS. NIDR,BRB,LCDO,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1995 VL 10 SU 1 BP S177 EP S177 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN484 UT WOS:A1995RN48400155 ER PT J AU BAINES, IC CORIGLIANOMURPHY, A KORN, ED AF BAINES, IC CORIGLIANOMURPHY, A KORN, ED TI QUANTIFICATION AND LOCALIZATION OF PHOSPHORYLATED MYOSIN-I ISOFORMS IN ACANTHAMOEBA-CASTELLANII SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEAVY-CHAIN KINASE; INTRACELLULAR-LOCALIZATION; PLASMA-MEMBRANES; BRUSH-BORDER; ACTIN; BINDING; IMMUNOFLUORESCENCE; MICROSCOPY; ACTIVATION; SEQUENCE AB The actin-activated Mg2+-ATPase activities of the three myosin I isoforms in Acanthamoeba castellanii are significantly expressed only after phosphorylation of a single site in the myosin I heavy chain. Synthetic phosphorylated and unphosphorylated peptides corresponding to the phosphorylation site sequences, which differ for the three myosin I isoforms, were used to raise isoform-specific antibodies that recognized only the phosphorylated myosin I or the total myosin I isoform (phosphorylated and unphosphorylated), respectively. With these antisera, the amounts of total and phosphorylated isoform were quantified, the phosphomyosin I isoforms localized, and the compartmental distribution of the phosphomyosin isoforms determined. Myosin IA, which was almost entirely in the actin-rich cortex, was 70-100% phosphorylated and particularly enriched under phagocytic cups. Myosins IB and were predominantly associated with plasma membranes and large vacuole membranes, where they were only 10-20% phosphorylated, whereas cytoplasmic myosins IB and IC, like cytoplasmic myosin IA, were mostly phosphorylated (60-100%). Moreover, phosphomyosin IB was concentrated in actively motile regions of the plasma membrane. More than 20-foId more phosphomyosin IC and 10-fold more F-actin were associated with the membranes of contracting contractile vacuoles (CV) than of filling CVs. As the total amount of CV-associated myosin IC remained constant, it must be phosphorylated at the start of CV contraction. These data extend previous proposals for the specific functions of myosin I isozymes in Acanthamoeba (Baines, I. C., H. Brzeska, and E. D. Kern. 1992. J. Cell Biol. 119:1193-1203): phosphomyosin IA in phagocytosis, phosphomyosin IB in phagocytosis and pinocytosis, and phosphomyosin IC in contraction of the CV. RP NHLBI, CELL BIOL LAB, BLDG 3, RM B1-22, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 40 TC 53 Z9 53 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1995 VL 130 IS 3 BP 591 EP 603 DI 10.1083/jcb.130.3.591 PG 13 WC Cell Biology SC Cell Biology GA RL496 UT WOS:A1995RL49600009 PM 7622560 ER PT J AU SENTERRELESENFANTS, S ALAG, AS SOBEL, ME AF SENTERRELESENFANTS, S ALAG, AS SOBEL, ME TI MULTIPLE MESSENGER-RNA SPECIES ARE GENERATED BY ALTERNATE POLYADENYLATION FROM THE HUMAN CALMODULIN-I GENE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ADENINE RICH ELEMENTS; 3 RAPID AMPLIFICATION OF COMPLEMENTARY ENDS; CALMODULIN; POLYADENYLATION ID MESSENGER-RNA DEGRADATION; ENCODING HUMAN CALMODULIN; 3' UNTRANSLATED REGION; NUCLEOTIDE-SEQUENCE; CELL-LINES; RAT; PROTEIN; LOCALIZATION; EXPRESSION; PSEUDOGENE AB Three distinct genes encode an identical calmodulin protein in mammalian cells. In addition, multiple mRNA transcripts, with approximate sizes of 1.6 kb and 4.4 kb, are visualized on Northern blots hybridized to calmodulin-1 cDNA probes. To elucidate the mechanism generating multiple calmodulin mRNAs, the complete sequence of the 4194 base human calmodulin-1 mRNA was determined from cDNA clones and 3' rapid amplification of complementary ends (3' RACE). The 5' untranslated region of calmodulin-1 mRNA contains a GC-rich domain containing multiple repeats of GGC interrupted by a GCA sequence, as well as a tandem repeat sequence of eight GCA triplets. The 3' untranslated region of calmodulin-1 mRNA contains two canonical and one aberrant (ATTAAA) polyadenylation signal, consistent with the sizes of 1.6 kb and 4.4 kb mRNAs visualized on Northern blots, and a potential minor 4.2 kb mRNA detected by 3' RACE. Hybridization experiments using specific probes upstream and downstream of the polyadenylation signals demonstrated that alternate use of polyadenylation signals is the molecular mechanism for multiple calmodulin-1 mRNA transcripts in human cells. Thirteen adenine rich elements with the motif AUUUA were detected in the 3' untranslated region. Three such motifs are embedded in regions that are conserved with the rat 3' untranslated region of calmodulin-1 mRNA. One of these is surrounded by an adenine-uridine rich region that can form an 11-base pair stem structure. We propose that sequences in the 3' untranslated region of calmodulin-1 mRNA may play a role in the regulation of calmodulin expression. (C) 1995 Wiley-Liss, Inc. C1 NCI,PATHOL LAB,MOLEC PATHOL SECT,BETHESDA,MD 20892. NR 37 TC 17 Z9 17 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG PY 1995 VL 58 IS 4 BP 445 EP 454 DI 10.1002/jcb.240580407 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RU727 UT WOS:A1995RU72700006 PM 7593266 ER PT J AU BARNES, DM SYKES, DB SMITH, JJ MILLER, DS AF BARNES, DM SYKES, DB SMITH, JJ MILLER, DS TI MAGNESIUM-DEPENDENT STIMULATION OF PROTEIN-SYNTHESIS BY THE INSULIN MIMIC, PERVANADATE SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID XENOPUS-LAEVIS OOCYTES; GUANINE-NUCLEOTIDES; RECEPTOR KINASE; RAT ADIPOCYTES; VANADATE; GLUCOSE; TRANSLATION; ACTIVATION; HORMONE; CELLS AB The insulin mimic, peroxide of vanadate (pervanadate), stimulated S-35-methionine incorporation into Xenopus oocyte protein in a Mg2+-dependent manner. Reducing the extracellular Mg2+ concentration from 1.0 to 0.1 mM decreased the pervanadate-stimulated component of incorporation by 35%; with 0.01 mM Mg2+ or lower, the pervanadate-stimulated component was abolished. In addition, reducing extracellular Mg2+ to 0.01 mM inhibited about 50% of the insulin-stimulated component of methionine incorporation. Mg2+ depletion had no effects on incorporation in controls or when protein synthesis was stimulated by Zn2+ or bovine growth hormone. Thus, not all substances that stimulated protein synthesis showed a dependence on extracellular Mg2+. Reducing extracellular Ca2+ had no effects on methionine incorporation in control cells or in cells stimulated by pervanadate or insulin. When oocytes maintained in a paraffin oil medium were brought into contact with a 0.5 mu l droplet of buffer containing the Mg2+ indicator dye, mag-fura-2, and pervanadate, apparent droplet Mg2+ decreased rapidly, indicating net uptake by the cells. insulin also caused a net uptake of Mg2+. In contrast, apparent extracellular Mg2+ was constant when cells were in contact with droplets containing no effecters. Together, these data indicate that extracellular Mg2+, but not Ca2+, is involved in the stimulation of protein synthesis by pervanadate, and to a lesser extent by insulin. Pervanadate appears to induce a net uptake of Mg2+, and this change in membrane transport may be an early event in signalling the increase in translation. (C) 1995 Wiley-Liss, Inc.(**) C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 36 TC 3 Z9 3 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1995 VL 164 IS 2 BP 304 EP 314 DI 10.1002/jcp.1041640211 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RK702 UT WOS:A1995RK70200010 PM 7542661 ER PT J AU TANAKA, H LIANG, CT AF TANAKA, H LIANG, CT TI EFFECT OF PLATELET-DERIVED GROWTH-FACTOR ON DNA-SYNTHESIS AND GENE-EXPRESSION IN BONE-MARROW STROMAL CELLS DERIVED FROM ADULT AND OLD RATS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID COLLAGEN MESSENGER-RNA; FACTOR-I; DEVELOPMENTAL EXPRESSION; ALKALINE-PHOSPHATASE; FORMATION INVITRO; CDNA CLONING; AGED RATS; OSTEOPONTIN; CULTURES; MATRIX AB The effects of platelet-derived growth factor (PDGF) on DNA synthesis and mRNA expression of osteoblast markers in marrow stromal cells derived from adult (6 months) and old (24 months) rats were examined. Treatment of stromal cells from adult rats with dexamethasone induced the appearance of osteoblast-like cells. PDGF partially also inhibited the differentiation of stromal cells induced by dexamethasone. In cultures of serum-starved stromal cells, PDGF stimulated [H-3]-thymidine incorporation into DNA in a dose-dependent manner with a maximum stimulation of 15-fold at 500 ng/ml. By comparison, insulin-like growth factor (IGF-I) has a small effect on [H-3]-thymidine incorporation. The effect of PDGF and IGF-I on DNA synthesis was additive. Treatment of the confluent stromal cells from adult rats with PDGF increased the mRNA level of osteopontin fourfold without any significant effect on alkaline phosphatase and type I collagen mRNAs. In contrast, dexamethasone stimulated the mRNA expression of alkaline phosphatase, type I collagen, and osteopontin 2.1-, 2.3-, and 14-fold, respectively. Addition of PDGF to dexamethasone-treated cells failed to induce any further increase in osteopontin expression whereas the expression of alkaline phosphatase and type I collagen was partially reduced. The expression of osteocalcin mRNA was negligible in stromal cells but stimulated several fold by dexamethasone and 1,25(OH)(2)D-3. PDGF inhibited drastically the elevation of osteocalcin mRNA. In contrast, IGF-I stimulated type I collagen expression 100% without any appreciable effect on the expression of osteopontin and alkaline phosphatase. The stimulatory effect of PDGF on osteopontin expression was augmented by IGF-I. Furthermore, PDGF attenuated the stimulatory effect of IGF-I on type I collagen expression. The responses of cultured cells from old rats to growth factors were also examined. PDGF or PDGF plus IGF-I increased [H-3]-thymidine incorporation in stromal cells from old rats but to a lesser extent. However, PDGF was equally effective in stimulating osteopontin expression in cells from both adult and old rats. We concluded that PDGF is a potent mitogen but that the response of stromal cells from old rats is impaired. In addition, PDGF stimulates osteopontin expression in stromal cells and this effect is not age dependent. (C) 1995 Wiley-Liss, Inc.(**) C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 41 TC 39 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1995 VL 164 IS 2 BP 367 EP 375 DI 10.1002/jcp.1041640217 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RK702 UT WOS:A1995RK70200016 PM 7622582 ER PT J AU MIRSKY, AF AF MIRSKY, AF TI PERILS AND PITFALLS ON THE PATH TO NORMAL POTENTIAL - THE ROLE OF IMPAIRED ATTENTION - HOMAGE TO BIRCH,HERBERT,G SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID SCHIZOPHRENIA AB The research of Herbert Birch and colleagues, conducted 30 years ago in a rural area of Guatemala, called attention to the permanent noxious effects on cognitive development associated with conditions of poverty. Half of the world's population, including millions of persons in the United States, are still afflicted by these conditions. Included among these are malnutrition, disease, toxic agents, perinatal injury, and lack of intellectual/social stimulation. Recent research findings on the cognitive effects of these poverty-related variables are presented; the effects appeal to be expressed in a reduction of the brain's capacity to engage in attentive behavior. Neuropsychologists, by virtue of their interests and training, are in a position to develop methods of assessing and correcting these deficits, and must become advocates of improved conditions to foster better brain development for all of the world's children. RP MIRSKY, AF (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,CLIN & EXPTL NEUROPSYCHOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 12 Z9 12 U1 0 U2 1 PU SWETS ZEITLINGER BV PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD AUG PY 1995 VL 17 IS 4 BP 481 EP 498 DI 10.1080/01688639508405140 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA RQ803 UT WOS:A1995RQ80300001 PM 7593470 ER PT J AU KOSMIDIS, MH FANTIE, BD AF KOSMIDIS, MH FANTIE, BD TI IMPAIRED AVOIDANCE-LEARNING AFTER CLOSED-HEAD INJURY - DISSOCIATION BETWEEN 2 TASKS DUE TO CLASSICAL-CONDITIONING SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID ANTICIPATORY BEHAVIOR DEFICITS; ATTENTION; SEQUELAE; DYSFUNCTION; CHILDREN; RECOVERY; BRAIN AB Like controls, a Closed-Head Injury (CHI) group learned quickly to press a button during a 3-s warning stimulus in order to avoid a noxious buzzer. In a similar task, however, the CHI group had greater difficulty achieving the learning criterion compared to controls when required to prevent an innocuous visual display (i.e., a circle). The difficulty levels of these two avoidance tasks were identical. The major differences concerned the temporal contiguity of the warning cue with the stimulus to be avoided and the intrinsic aversiveness of the buzzer compared to the appearance of a circle on a computer screen. We hypothesize that, although both tasks were operant in essential character, the buzzer may have produced a degree of classical conditioning. These results suggest that CHI survivors may have some difficulty forming connections between arbitrary stimuli when performance depends almost entirely upon conscious, effortful processing. When a stimulus is sufficiently noxious to be capable of producing an affective or autonomic response. however, automatic processes may aid in the formation of associations. C1 AMERICAN UNIV,HUMAN NEUROPSYCHOL LAB,WASHINGTON,DC 20016. RP KOSMIDIS, MH (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 53 TC 6 Z9 6 U1 1 U2 1 PU SWETS ZEITLINGER BV PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD AUG PY 1995 VL 17 IS 4 BP 622 EP 633 DI 10.1080/01688639508405150 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA RQ803 UT WOS:A1995RQ80300011 PM 7593480 ER PT J AU DOPPMAN, JL NIEMAN, LK CHANG, R YANOVSKI, J CUTLER, GB CHROUSOS, GP OLDFIELD, EH AF DOPPMAN, JL NIEMAN, LK CHANG, R YANOVSKI, J CUTLER, GB CHROUSOS, GP OLDFIELD, EH TI SELECTIVE VENOUS SAMPLING FROM THE CAVERNOUS SINUSES IS NOT A MORE RELIABLE TECHNIQUE THAN SAMPLING FROM THE INFERIOR PETROSAL SINUSES IN CUSHINGS-SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE AB The purpose of this study was to compare ACTH levels in unstimulated samples obtained from the cavernous sinuses (CS) to unstimulated and CRH-stimulated samples obtained from the inferior petrosal sinuses (IPS) in 15 patients with surgically proven Cushing's disease. After unstimulated samples were obtained through 5-French catheters placed in both IPS, tracker catheters were introduced into both cavernous sinuses, and unstimulated samples were obtained within 5 min of the initial set. The Tracker catheters were removed, CRH was administered, and CRH-stimulated samples were obtained from the IPS. We compared the central to peripheral ACTH ratios in unstimulated samples from the cavernous sinuses to unstimulated and CRH-stimulated samples from the IPS as a basis for distinguishing pituitary from ectopic ACTH production. In addition, we compared the ability of the intercavernous and interpetrosal ACTH ratios to correctly predict the site of the microadenoma. Unstimulated levels of ACTH in the cavernous sinuses were generally higher than unstimulated levels of ACTH in the petrosal sinuses. However, 3 of 15 patients failed to show central to peripheral ACTH ratios greater than 2 in unstimulated samples from the cavernous sinuses and were thus falsely negative for the diagnosis of Cushing's disease (test sensitivity, 80%). By comparison, the test sensitivity for the petrosal sinus samples was 87% for the unstimulated samples and 100% for the CRH-stimulated samples. Lateralization was correct in 6 of 15 patients based on CS samples and in 9 of 15 patients based on IPS samples. Because of the 20% false negative rate, CS sampling without CRH stimulation is not recommended for the differential diagnosis of ACTH-dependent hypercortisolism. C1 NICHHD, WARREN GRANT MAGNUSON CLIN CTR, HENRY M JACKSON FDN, DEPT RADIOL, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NR 9 TC 46 Z9 46 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 AUG PY 1995 VL 80 IS 8 BP 2485 EP 2489 DI 10.1210/jc.80.8.2485 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN312 UT WOS:A1995RN31200036 PM 7629247 ER PT J AU LATRONICO, AC ANASTI, J ARNHOLD, IJP MENDONCA, BB DOMENICE, S ALBANO, MC ZACHMAN, K WAJCHENBERG, BL TSIGOS, C AF LATRONICO, AC ANASTI, J ARNHOLD, IJP MENDONCA, BB DOMENICE, S ALBANO, MC ZACHMAN, K WAJCHENBERG, BL TSIGOS, C TI A NOVEL MUTATION OF THE LUTEINIZING-HORMONE RECEPTOR GENE CAUSING MALE GONADOTROPIN-INDEPENDENT PRECOCIOUS PUBERTY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONSTITUTIVELY ACTIVATING MUTATION; THYROTROPIN TSH RECEPTOR; 3RD CYTOPLASMIC LOOP; RAT; PHOSPHOINOSITIDE; LH AB Familial male-limited precocious puberty (FMPP) is an autosomal dominant gonadotropin-independent disorder. Affected males generally develop signs of precocious puberty in early childhood. They typically show Leydig cell hyperplasia and increased testosterone production typical for their age, whereas circulating LH concentrations remain prepubertal. Several dominant point mutations of the LH receptor gene were identified in pedigrees with familial male-limited precocious puberty and were shown to cosegregate with the disease. Here we report a novel heterozygote point mutation in the LH receptor gene of a Brazilian boy with gonadotropin-independent precocious puberty. This mutation substitutes alanine 568 with valine at the carboxyterminus of the third cytosolic loop of the LH receptor. The unoccupied mutant receptors confer constitutive activation of adenyl cyclase activity when expressed in COS-7 cells, resulting in 4-fold higher cAMP concentrations over baseline compared with cells expressing an equivalent number of wild-type receptors. The affinity of the mutant receptors to I-125-labeled human LH was not altered compared with the wild type. Mutations of the homologue alanine residue in the alpha(1)-adrenergic (in vitro), FSH (in vitro), and TSH (naturally occurring) receptors also result in constitutive adenyl cyclase activation, suggesting that this alanine residue is crucial for signal transduction and a potential site for upregulatory/oncogenic mutations in G-protein coupled receptors. C1 UNIV SAO PAULO, HOSP CLIN, DIV ENDOCRINOL, BR-05403 SAO PAULO, BRAZIL. RP LATRONICO, AC (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Mendonca, Berenice/C-2827-2012; ARNHOLD, IVO/D-2672-2012; Domenice, Sorahia/J-6959-2015; OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X NR 22 TC 86 Z9 93 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1995 VL 80 IS 8 BP 2490 EP 2494 DI 10.1210/jc.80.8.2490 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RN312 UT WOS:A1995RN31200037 PM 7629248 ER PT J AU PINTO, LA SULLIVAN, J BERZOFSKY, JA CLERICI, M KESSLER, HA LANDAY, AL SHEARER, GM AF PINTO, LA SULLIVAN, J BERZOFSKY, JA CLERICI, M KESSLER, HA LANDAY, AL SHEARER, GM TI ENV-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES IN HIV SERONEGATIVE HEALTH-CARE WORKERS OCCUPATIONALLY EXPOSED TO HIV-CONTAMINATED BODY-FLUIDS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIV-SPECIFIC CTL; CLASS I-RESTRICTED CTL; T HELPER RESPONSES; HIV-EXPOSED HEALTH CARE WORKERS ID SEROPOSITIVE INDIVIDUALS; IMMUNE-RESPONSE; ENVELOPE GLYCOPROTEIN; AUTOIMMUNE-DISEASE; PERIPHERAL-BLOOD; DENDRITIC CELLS; VIRUS; INFECTION; PEPTIDE; CHILDREN AB Identification of the components of protective immunity are crucial for the development of effective prophylactic and therapeutic vaccine strategies, Analysis of HIV-specific responses in exposed but uninfected individuals might thus provide a unique resource to elucidate the components and correlates of protective immunity to HIV. In the present study we analyzed HIV-specific cytotoxic and helper T lymphocyte responses in health care workers (HCW) exposed to body fluids from HIV-positive individuals, HCW exposed to blood from HIV-negative individuals as well as healthy donors served as controls, Cytotoxic T lymphocyte (CTL) responses to HIV envelope (env) peptides were detected in 7/20 (35%) HCW exposed to HIV-positive blood and in none of the 20 health care workers exposed to uninfected blood or the seven healthy blood donors studied, HIV-specific CTL responses were detected only after in vitro stimulation, and were MHC class I restricted, No MHC class I restriction elements were uniformly identified among the different responders, 21/28 (75%) HCW exposed to contaminated blood responded to env as measured by IL-2 production to the peptides, in contrast to only 9/38 (24%) HCW exposed to HIV seronegative blood and 3/35 (9%) healthy blood donors. All the HIV exposed individuals were seronegative on repeated ELISA tests, and no evidence of infection was obtained by PCR analysis, These findings indicate that a single exposure to HIV can induce CTL immunity to HIV antigens, in the absence of other evidence of infection. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NCI, METAB BRANCH, BETHESDA, MD 20892 USA. RUSH PRESBYTERIAN ST LUKES MED CTR, DEPT IMMUNOL MICROBIOL, CHICAGO, IL 60612 USA. RUSH PRESBYTERIAN ST LUKES MED CTR, DEPT MED, CHICAGO, IL 60612 USA. UNIV MILAN, CATTEDRA IMMUNOL, MILAN, ITALY. NR 71 TC 205 Z9 207 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 AUG PY 1995 VL 96 IS 2 BP 867 EP 876 DI 10.1172/JCI118133 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600027 PM 7635981 ER PT J AU MCMAHON, JP WHEAT, J SOBEL, ME PASULA, R DOWNING, JF MARTIN, WJ AF MCMAHON, JP WHEAT, J SOBEL, ME PASULA, R DOWNING, JF MARTIN, WJ TI MURINE LAMININ BINDS TO HISTOPLASMA-CAPSULATUM - A POSSIBLE MECHANISM OF DISSEMINATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ATTACHMENT SITES; YEASTS; EXTRACELLULAR MATRIX; GLYCOPROTEINS; IMMUNOSUPPRESSION ID BASEMENT-MEMBRANE LAMININ; HIGH-AFFINITY BINDING; STAPHYLOCOCCUS-AUREUS; HELICOBACTER-PYLORI; ESCHERICHIA-COLI; CELL ATTACHMENT; MONOCLONAL-ANTIBODIES; SYNTHETIC PEPTIDE; MAMMALIAN-CELLS; PROTEINS AB Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues, In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner, Scatchard analysis with I-125-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent K-d for laminin binding of 1.6 x 10(-9) M, Laminin binding to H, capsulatum was decreased from 62+/-1 to 17+/-1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin, A. 50-kD H, capsulatum laminin-binding protein was demonstrated using an I-125-Ln blot of H. capsulatum cell wall proteins, The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related, This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane. C1 INDIANA UNIV,SCH MED,DEPT MED,DIV PULM & CRIT CARE MED,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT PATHOL,DIV INFECT DIS,INDIANAPOLIS,IN 46202. NCI,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-43524, HL-46647, HL-51962] NR 42 TC 48 Z9 48 U1 1 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 AUG PY 1995 VL 96 IS 2 BP 1010 EP 1017 DI 10.1172/JCI118086 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600043 PM 7635937 ER PT J AU SCALA, S BUDILLON, A ZHAN, ZR CHOCHUNG, YS JEFFERSON, J TSOKOS, M BATES, SE AF SCALA, S BUDILLON, A ZHAN, ZR CHOCHUNG, YS JEFFERSON, J TSOKOS, M BATES, SE TI DOWN-REGULATION OF MDR-1 EXPRESSION BY 8-CL-CAMP IN MULTIDRUG-RESISTANT MCF-7 HUMAN BREAST-CANCER CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE P-GLYCOPROTEIN; PROTEIN KINASE A; MDR; CAMP; REVERSAL ID DEPENDENT PROTEIN-KINASE; P-GLYCOPROTEIN EXPRESSION; HL-60 LEUKEMIA-CELLS; DRUG-RESISTANCE; GENE-EXPRESSION; 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE; INDUCED-DIFFERENTIATION; GROWTH-INHIBITION; CARCINOMA-CELLS; RAT-LIVER AB 8-Cl-cAMP, a site-selective analogue of cAMP, decreased mdr-1 expression in multidrug-resistant human breast cancer cells, A sixfold reduction of mdr-1 mRNA expression by 8-Cl-cAMP began within 8 h of treatment and was associated with a decrease in the synthesis of P-glycoprotein and with an increase in vinblastine accumulation A reduction in mdr-1 expression after. 8-Cl-cAMP treatment was also observed in multidrug-resistant human ovarian cancer cell hues, 8-Cl-cAMP is known to change the ratio between the two regulatory subunits, RI and RII, of protein kinase A (pKA), We observed that RI alpha decreased within 24 h of 8-Cl-cAMP treatment, that RII beta increased after as few as 3 h of treatment, and that PKA catalytic activity remained unchanged during 48 h of 8-Cl-cAMP treatment, The results are consistent with the hypothesis that mdr-1 expression is regulated in part by changes in PKA isoenzyme levels, Although 8-Cl-cAMP has been used to differentiate cells in other model systems, the only differentiating effect that could be detected after 8-Cl-cAMP treatment in the MCF-7TH cells was an increase in cytokeratin expression, Evil dence that the reduction of mdr-1 mRNA occurred at the level of gene transcription was obtained by measuring chloramphenicol acetyltransfer;ase (CAT) mRNA in MCF-7TH cells transfected with an mdr-1 promoter-CAT construct prior to 8-Cl-cAMP treatment, Thus, 8-Cl-cAMP is able to downregulate mdr-1 expression and suggests a new approach to reversal of drug resistance in human breast cancer. C1 NCI, MED BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, PATHOL LAB, BETHESDA, MD 20892 USA. NCI, DIV CANC BIOL DIAG & CTR, TUMOR IMMUNOL & BIOL LAB, BETHESDA, MD 20892 USA. RI Scala, Stefania/K-1380-2016; OI Scala, Stefania/0000-0001-9524-2616; Budillon, Alfredo/0000-0002-6330-6053 NR 58 TC 45 Z9 46 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1995 VL 96 IS 2 BP 1026 EP 1034 DI 10.1172/JCI118088 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600045 PM 7543490 ER PT J AU MACIEJEWSKI, JP SELLERI, C SATO, T CHO, HJ KEEFER, LK NATHAN, CF YOUNG, NS AF MACIEJEWSKI, JP SELLERI, C SATO, T CHO, HJ KEEFER, LK NATHAN, CF YOUNG, NS TI NITRIC-OXIDE SUPPRESSION OF HUMAN HEMATOPOIESIS IN-VITRO - CONTRIBUTION TO INHIBITORY-ACTION OF INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BONE MARROW; CYTOKINES; NITRIC OXIDE SYNTHASE; CD34(+) CELLS; APLASTIC ANEMIA ID L-ARGININE; APLASTIC-ANEMIA; BONE-MARROW; MYELODYSPLASTIC SYNDROMES; ANTIGENIC ANALYSIS; PROGENITOR CELLS; SYNTHASE; INVITRO; MACROPHAGES; EXPRESSION AB IFN-gamma and TNF-cu, potent inhibitors of hematopoiesis, induce nitric oxide synthase (NOS) in various cell types. When normal human bone marrow (BM) or CD34(+) cells were exposed to NO, inhibition of colony formation was dose dependent and direct, NO induced apoptosis in BM progenitors, as shown by electrophoretic detection of DNA degradation and deoxynucleotidyl transferase assay, Using PCR and immunoprecipitation, we found inducible NOS (iNOS) mRNA and iNOS protein in BM after stimulation with IFN-gamma or TNF-alpha. iNOS mRNA was also detected by PCR in highly purified CD34(+) cells; TNF-alpha or lFN-gamma increased NOS expression. The presence of iNOS in CD34(+) cells was confirmed in single cells by immunochemical staining. N-G-Monomethyl-L-arginine (MM-Arg), an NOS inhibitor, partially reversed the effects of TNF-cu and, to a lesser extent, IFN-gamma in methylcellulose culture of total BM and CD34(+) cells, and inhibited apoptosis of BM cells induced by these cytokines, When the effects of competitive iNOS inhibition were tested on more immature progenitors, MM-Arg increased the number of long-term BM culture-initiating cells in control cultures but failed to protect these cells from the inhibitory action of IFN-gamma and TNF-alpha. Our results suggest that NIO may be one mediator of cytokine-induced hematopoietic suppression. C1 CORNELL UNIV,COLL MED,DIV HEMATOL ONCOL,NEW YORK,NY 10021. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP MACIEJEWSKI, JP (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,7C106,BETHESDA,MD 20892, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 63 TC 167 Z9 171 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 AUG PY 1995 VL 96 IS 2 BP 1085 EP 1092 DI 10.1172/JCI118094 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600051 PM 7543491 ER PT J AU MANN, WA LOHSE, P GREGG, RE RONAN, R HOEG, JM ZECH, LA BREWER, HB AF MANN, WA LOHSE, P GREGG, RE RONAN, R HOEG, JM ZECH, LA BREWER, HB TI DOMINANT EXPRESSION OF TYPE-III HYPERLIPOPROTEINEMIA - PATHOPHYSIOLOGICAL INSIGHTS DERIVED FROM THE STRUCTURAL AND KINETIC CHARACTERISTICS OF APOE-1(LYS(146)-]GLU) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ATHEROSCLEROSIS; DYSBETALIPOPROTEINEMIA; IN VIVO KINETICS; LOW DENSITY LIPOPROTEIN (APO-B, APOE); RECEPTOR BINDING; HEPARIN BINDING ID LOW-DENSITY-LIPOPROTEIN; HUMAN APOLIPOPROTEIN-E; HEPARAN-SULFATE PROTEOGLYCANS; FIBROBLAST GROWTH-FACTOR; HIGH-AFFINITY RECEPTOR; HUMAN-E APOPROTEIN; FAMILIAL DYSBETALIPOPROTEINEMIA; CELL-SURFACE; HEPG2 CELLS; BINDING AB Type III hyperlipoproteinemia is characterized by delayed chylomicron and VLDL remnant catabolism and is associated with homozygosity for the apoE-2 allele. We have identified a kindred in which heterozygosity for an apoE mutant, apoE-1(Lys(146) --> Glu), is dominantly associated with the expression of type III hyperlipoproteinemia. DNA sequence analysis of the mutant apoE gene revealed a single-point mutation that resulted in the substitution of glutamic acid (GAG) for lysine (AAG) at residue 146 in the proposed receptor-binding domain of apoE, The pathophysiological effect of this mutation was investigated in vivo by kinetic studies in the patient and six normal subjects, and in vitro by binding studies of apoE-1(Lys(146) --> Glu) to LDL receptors on human fibroblasts and to heparin. The kinetic studies revealed that apoE-1(Lys(146) --> Glu) was catabolized significantly slower than apoE-3 in normals (P < 0.005), In the proband, the plasma residence times of both apoEs were substantially longer and the production rate of total apoE was about two times higher than in the control subjects, ApoE-1(Lys(146) --> Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3, The affinity of apoE-1(Lys(146) --> Glu) to heparin was also markedly reduced compared with both apoE-2(Arg(158) --> Cys) and apoE-3. These abnormal in vitro binding characteristics and the altered in vivo metabolism of apoE-1(Lys(146) --> Glu) are proposed to result in the functional dominance of this mutation in the affected kindred. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 63 TC 19 Z9 19 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 AUG PY 1995 VL 96 IS 2 BP 1100 EP 1107 DI 10.1172/JCI118096 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RM466 UT WOS:A1995RM46600053 PM 7635945 ER PT J AU CONVILLE, PS ANDREWS, JWB WITEBSKY, FG AF CONVILLE, PS ANDREWS, JWB WITEBSKY, FG TI EFFECT OF PANTA ON GROWTH OF MYCOBACTERIUM-KANSASII IN BACTEC 12B MEDIUM SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RADIOMETRIC METHOD; SPECIMENS; RECOVERY AB Mycobacterium kansasii isolates from two patients showed relatively slow growth in BACTEC 12B medium (12B) (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) compared with the more rapid growth of these isolates on solid media, This finding prompted an evaluation of the effect of PANTA (Becton Dickinson) on the growth rate of these isolates, Suspensions of one isolate from each of these two patients (A and B), six additional isolates from six other; patients (C through H), and one M. kansasii American Type Culture Collection isolate were inoculated into 12B with PANTA, 12B with reconstituting fluid only and Middlebrook 7H11 agar plates (Remel, Lenexa, Kans,). For the isolates from patients A and B, the average times to detection for 12B with PANTA, 12B with reconstituting fluid, and Middlebrook 7H11 agar were 12.3, 7.4, and 9.0 days, respectively, For the remaining six patient isolates and the American Type Culture Collection strain, the average times to detection for these media were 9.2, 8.1, and 9.6 days, Susceptibility tests performed with the isolates from patients A and B with the individual component antibiotics of PANTA and testing of four of the other isolates with nalidixic acid alone suggested that nalidxic acid exerts some degree of inhibition on the growth of M. kansasii, The eight patient isolates were also inoculated onto Lowenstein Jensen medium (Remel) and onto a variety of selective mycobacterial media containing nalidixic acid and other antimicrobial agents, All isolates showed some degree of inhibition on at least one of these selective media. RP CONVILLE, PS (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 6 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1995 VL 33 IS 8 BP 2012 EP 2015 PG 4 WC Microbiology SC Microbiology GA RJ052 UT WOS:A1995RJ05200008 PM 7559939 ER PT J AU SECCHIERO, P ZELLA, D CROWLEY, RW GALLO, RC LUSSO, P AF SECCHIERO, P ZELLA, D CROWLEY, RW GALLO, RC LUSSO, P TI QUANTITATIVE PCR FOR HUMAN HERPESVIRUS-6 AND HERPESVIRUS-7 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; MARROW TRANSPLANTATION; HUMAN CYTOMEGALOVIRUS; MESSENGER-RNA; CELLULAR DNA; INFECTION; VIRUS; ANTIBODY; QUANTIFICATION; EXPRESSION AB A quantitative PCR assay for the detection of human herpesvirus 6 (HHV-6) (variants A and B) and HHV-7 DNAs in clinical samples was developed. The assay uses a nonhomologous internal standard (IS) for each virus that is coamplified with the wild-type target sequence in the same vial and with the same pair of primers. This method allows for a correction of the variability of efficiency of the PCR technique. A standard curve is constructed for each experiment by coamplification of known quantities of the cloned HHV-6 or HHV-7 target templates with the respective IS. Absolute quantitation of the test samples is then achieved by determining the viral target/IS ratio of the hybridization signals of the amplification products and plotting this value against the standard curve. Using this assay, we quantitated the amount of HHV-6 or HHV-7 DNA in infected cell cultures and demonstrated an inhibitory effect of phosphonoformic acid on the replication of HHV-6 and HHV-7 in vitro. As the first clinical application of this procedure, we performed preliminary measurements of the loads of HHV-6 and HHV-7 in lymph nodes from patients with Hodgkin's disease and AIDS. Application of this quantitative PCR method should be helpful for elucidating the pathogenic roles of HHV-6 and HHV-7. RP SECCHIERO, P (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,37 CONVENT DR,MSC-4255,BETHESDA,MD 20892, USA. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 47 TC 65 Z9 66 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1995 VL 33 IS 8 BP 2124 EP 2130 PG 7 WC Microbiology SC Microbiology GA RJ052 UT WOS:A1995RJ05200029 PM 7559960 ER PT J AU BAILEY, J PLUDA, JM FOLI, A SAVILLE, MW BAUZA, S ADAMSON, PC MURPHY, RF COHEN, RB BRODER, S YARCHOAN, R AF BAILEY, J PLUDA, JM FOLI, A SAVILLE, MW BAUZA, S ADAMSON, PC MURPHY, RF COHEN, RB BRODER, S YARCHOAN, R TI PHASE I/II STUDY OF INTERMITTENT ALL-TRANS-RETINOIC ACID, ALONE AND IN COMBINATION WITH INTERFERON ALFA-2A, IN PATIENTS WITH EPIDEMIC KAPOSIS-SARCOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE PROMYELOCYTIC LEUKEMIA; IMMUNE-DEFICIENCY SYNDROME; HOMOSEXUAL MEN; CELL-LINE; THERAPY; DIFFERENTIATION; REPLICATION; EXPRESSION; HIV-1 AB purpose: A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Patients and Methods: Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/mu L, were entered. The protocol initially called for patients to receive 150 mg/m(2)/d of ATRA every other week. However, this regimen wets associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m(2)/d orally in three divided doses, increasing to a maximum of 100 mg/m(2)/d. After 12 weeks, IFN alfa-2a could be added. Results: The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had a partial response (PR), There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebovfided when treatment was resumed after a week without the drug. Conclusion: Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy, However, we were unable to document antitumor activity in patients with HIV-associated KS. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. NR 50 TC 37 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1995 VL 13 IS 8 BP 1966 EP 1974 PG 9 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300017 PM 7636537 ER PT J AU WILSON, WH JAMISDOW, C BRYANT, G BALIS, FM KLECKER, RW BATES, SE CHABNER, BA STEINBERG, SM KOHLER, DR WITTES, RE AF WILSON, WH JAMISDOW, C BRYANT, G BALIS, FM KLECKER, RW BATES, SE CHABNER, BA STEINBERG, SM KOHLER, DR WITTES, RE TI PHASE-I AND PHARMACOKINETIC STUDY OF THE MULTIDRUG-RESISTANCE MODULATOR DEXVERAPAMIL WITH EPOCH CHEMOTHERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; NON-HODGKINS-LYMPHOMA; DRUG-RESISTANCE; VERAPAMIL; VINCRISTINE; ADRIAMYCIN; CYCLOSPORINE; ETOPOSIDE; EFFICACY; TRIAL AB Purpose: Dexverapamil is a competitive inhibitor of the P-glycoprotein (Pgp) efflux pump, a potent mechanism of multidrug resistance (mdr-1) in vitro. We performed a phase I study to determine the maximvm-tolerated dose (MTD) and pharmacokinetics of dexverapamil with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. Patients and Methods: Eligible patients had relapsed or refractory lymphoma or sarcoma. Patients initially received EPOCH alone, and those with stable or progressive disease were crossed-over to received dexverapamil on subsequent cycles of EPOCH. Dexverapamil was administered orally for 6 days and escalated over eight dose levels ranging from 240 to 1,200 mg/m(2)/d. Pharmacokinetics of dexverapamil and its active metabolite, nor-dexverapamil, were obtained in most patients. In seven patients, pharmacokinetics of doxorubicin, doxorubicinol, and etoposide were determined on paired cycles of EPOCH with or without dexverapamil. Results: Sixty-five patients received 130 cycles of dexverapamil/EPOCH chemotherapy. The MTD of dexverapamil was 150 mg/m(2) every 4 hours (900 mg/m(2)/d), and hypotension was the principal dose-limiting toxicity. The dexverapamil area under the curve (AUG) increased proportionally with dexverapamil dose, but significant interpatient variation occurred. At the MTD, the median plasma overage concentrations of dexverapamil and nor-dexverapamil were 1.2 and 1.4 mu mol/L, respectively. Dexverapamil did not effect the steady-state concentration (C-ss) of etoposide, but increased the C-ss of doxorubicin and doxorubicinol nearly twofold. The absolute neutrophil and platelet nadirs were significantly lower on the dexverapamil cycles compared with cycles of EPOCH alone, but other chemotherapy-related toxicities did not change. Conclusion: The phase II recommended dose of dexverapamil with EPOCH is 150 mg/m(2) every 4 hours. This dose was well tolerated on an outpatient basis and achieved plasma concentrations of dexverapamil and nor-dexverapamil within the effective range for Pgp inhibition in vitro. Although dexverapamil increased the hematopoietic toxicity of EPOCH, it was mild, readily reversible, and offset by EPOCH dose reductions. Dexverapamil should be considered for further study. RP WILSON, WH (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 10,RM 12N-226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 65 Z9 66 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 AUG PY 1995 VL 13 IS 8 BP 1985 EP 1994 PG 10 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300019 PM 7636539 ER PT J AU WILSON, WH BATES, SE FOJO, A BRYANT, G ZHAN, Z REGIS, J WITTES, RE JAFFE, ES STEINBERG, SM HERDT, J CHABNER, BA AF WILSON, WH BATES, SE FOJO, A BRYANT, G ZHAN, Z REGIS, J WITTES, RE JAFFE, ES STEINBERG, SM HERDT, J CHABNER, BA TI CONTROLLED TRIAL OF DEXVERAPAMIL, A MODULATOR OF MULTIDRUG-RESISTANCE, IN LYMPHOMAS REFRACTORY TO EPOCH CHEMOTHERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; DRUG-RESISTANCE; P-GLYCOPROTEIN; MULTIPLE-MYELOMA; CELL-LINES; VERAPAMIL; EXPRESSION; CYCLOSPORINE; VINCRISTINE; ETOPOSIDE AB Purpose: Overexpression of the multidrug resistance gene (mdr-1) is present in vp to 60% of relapsed lymphomas. To study its role in lymphomas, we conducted a controlled trial of dexverapamil, an inhibitor of the mdr-1 gene product, P-glycoprotein (Pgp), in lymphomas refractory to etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. Patients and Methods: Eligible patients had recurrent Hodgkin's (HD) or non-Hodgkin's lymphomas (NHL) and measurable disease. Patients initially received EPOCH alone and those with stable tumor over two cycles or progressive disease crossed over to receive dexverapamil and EPOCH on subsequent cycles. Dexverapamil was escalated eight dose levels, from 240 to 1,200 mg/m(2)/d. When possible, serial biopsies were obtained to measure mdr-1 expression by quantitative polymerase chain reaction (PCR). Results: Of 154 patients entered onto the trial, 109 had NHL and 45 had HD. The median age was 44 years, 67% had stage IV disease, and the median number of prior regimens was two (range, one to 12) in NHL and one (range, one to four) in HD. Sixty-four patients (42%) crossed over, of which eight were not assessable. The maximum-tolerated dose of dexverapamil was 900 mg/m(2)/d. Among 41 NHL patients (excluding mycosis fungoides), there were three complete responses (CRs) and two partial responses (PRs) (12%) and five minor responses (MRs); two of 10 HD patients achieved PRs. The mdr-1 level was measured in 44 biopsies from 19 patients. Pretherapy, mdr-1 was low (median, 2.5 U) but increased (median, 12.2 U) at crossover. Of six patients with mdr-1 levels greater than 15 U, three responded to dexverapamil, while only one of eight patients with mdr-1 levels less than 15 U responded. EPOCH and dexverapamil were well tolerated, bur compared with EPOCH alone, produced more hematologic toxicity. Conclusion: These results suggest that Pgp plays a role in clinical drug resistance of lymphomas. However, they also suggest that mechanisms other than Pgp are prominent in heavily pretreated patients and that, although Pgp inhibition may be necessary, it is probably insufficient. Earlier intervention with dexverapamil may be more effective and warrants further study. RP WILSON, WH (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 10,ROOM 12N-226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 101 Z9 103 U1 0 U2 3 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 AUG PY 1995 VL 13 IS 8 BP 1995 EP 2004 PG 10 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300020 PM 7636540 ER PT J AU BERG, SL TOLCHER, A OSHAUGHNESSY, JA DENICOFF, AM NOONE, M OGNIBENE, FP COWAN, KH BALIS, FM AF BERG, SL TOLCHER, A OSHAUGHNESSY, JA DENICOFF, AM NOONE, M OGNIBENE, FP COWAN, KH BALIS, FM TI EFFECT OF R-VERAPAMIL ON THE PHARMACOKINETICS OF PACLITAXEL IN WOMEN WITH BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-I TRIAL; PLASMA-CONCENTRATIONS; OVARIAN-CANCER; TAXOL; RESISTANCE; INFUSION; VINCRISTINE; DAUNOMYCIN; EFFLUX; CELLS AB Purpose: To study the effect of the multidrug-resistance reversal agent R-verapamil on the pharmacokinetic behavior of poclitaxel. Methods: Six women with breast cancer who received paclitaxel as a 3-hour infusion with and without R-verapamil were monitored with frequent plasma sampling up to 24 hours postinfusion. Paclitaxel concentrations were measured using a reverse-phase high-pressure liquid chromatography assay. Results: Concomitant administration of R-verapamil resulted in a decrease in mean (+/- SD) paclitaxel clearonce from 179 +/- 67 mL/min/m(2) to 90 +/- 34 mL/min/m(2) (P < .03) and in a twofold increase in paclitaxel exposure (area under the curve [AUG]). The mean end-infusion paclitaxel concentration was also twofold higher: 5.1 +/- 1.8 mu mol/L versus 11.3 +/- 4.1 mu mol/L (P < .03). Conclusion: The alteration in paclitaxel pharmacokinetics when paclitaxel and R-verapamil are coadministered complicates the interpretation of response and toxicity data from clinical trials of this drug combination. (C) 1995 by American Society of Clinical Oncology. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,CTR CLIN,BETHESDA,MD 20892. NR 29 TC 62 Z9 62 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 AUG PY 1995 VL 13 IS 8 BP 2039 EP 2042 PG 4 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300026 PM 7636546 ER PT J AU ABRAMS, JS VENA, DA BALTZ, J ADAMS, J MONTELLO, M CHRISTIAN, M ONETTO, N DESMONDHELLMANN, S CANETTA, R FRIEDMAN, MA ARBUCK, SG AF ABRAMS, JS VENA, DA BALTZ, J ADAMS, J MONTELLO, M CHRISTIAN, M ONETTO, N DESMONDHELLMANN, S CANETTA, R FRIEDMAN, MA ARBUCK, SG TI PACLITAXEL ACTIVITY IN HEAVILY PRETREATED BREAST-CANCER - A NATIONAL-CANCER-INSTITUTE TREATMENT REFERRAL CENTER TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TAXOL; AGENT AB Purpose: To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. Patients and Methods: Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m(2) intravenously (IV) over 24 hours or at 135 mg/m(2) if they herd prior irradiation to 30% of marrow-bearing bone or ct cumulative dose of mitomycin greater than or equal to 20 mg/m(2). Results: In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [Cl], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. Conclusion: paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative core, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role if has in patients with less advanced disease. C1 BRISTOL MYERS SQUIBB,WALLINGFORD,CT. EMMES CORP,POTOMAC,MD. RP ABRAMS, JS (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,ROOM 741,BETHESDA,MD 20892, USA. NR 14 TC 131 Z9 131 U1 0 U2 3 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 AUG PY 1995 VL 13 IS 8 BP 2056 EP 2065 PG 10 WC Oncology SC Oncology GA RM473 UT WOS:A1995RM47300029 PM 7543562 ER PT J AU NOWJACKRAYMER, R AINAMO, J SUOMI, JD KINGMAN, A DRISCOLL, WS BROWN, LJ AF NOWJACKRAYMER, R AINAMO, J SUOMI, JD KINGMAN, A DRISCOLL, WS BROWN, LJ TI IMPROVED PERIODONTAL STATUS THROUGH SELF-ASSESSMENT - A 2-YEAR LONGITUDINAL-STUDY IN TEENAGERS SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE ORAL HYGIENE; SELF-CARE; PERIODONTAL DISEASES; ORAL HEALTH EDUCATION; BEHAVIORAL SCIENCE; DENTAL HYGIENIST ID DISEASE; PLAQUE; SCHOOLCHILDREN; HEALTH; DESIGN AB Short-term success of the use of self-assessment for motivating adults to improve their oral health status has been reported. The purpose of this trial was to evaluate the long-term effectiveness of two self-assessment strategies, one focused on gingival bleeding (group I) and another focused on plaque (group II). At baseline, 493 14- and 15-year-olds were assigned randomly to a group. Each subject was given a manual describing one of the self-assessment processes. Dental hygienists provided standardized classroom based instruction and two weeks later, individualized counselling. Examinations were conducted at baseline 6, 12, 18 and 24 months for gingival bleeding on probing, plaque, calculus, and probing depth; and at baseline and 24 months for recession and decayed, missing and filled surfaces (DMFS). Following the 12-month examination, subjects received an oral prophylaxis and individual counselling. The results revealed no statistically significant differences between groups for any clinical parameter at the final examination. However, the mean number of sites with gingival bleeding decreased steadily from baseline to 24 months with a 59% decrease and 55% decrease for groups I and II, respectively. This study suggests that self-assessment approaches can be effective in improving the long-term periodontal health status of teenagers. C1 UNIV HELSINKI,DEPT PERIODONTOL,SF-00300 HELSINKI,FINLAND. RP NOWJACKRAYMER, R (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,NATCHER BLDG,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD AUG PY 1995 VL 22 IS 8 BP 603 EP 608 DI 10.1111/j.1600-051X.1995.tb00812.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RM861 UT WOS:A1995RM86100004 PM 8583016 ER PT J AU KNABLE, MB RICKLER, K AF KNABLE, MB RICKLER, K TI PSYCHOSIS ASSOCIATED WITH FELBAMATE TREATMENT SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID RECEPTORS RP KNABLE, MB (reprint author), NIMH,DIV INTRAMURAL RES,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1995 VL 15 IS 4 BP 292 EP 293 DI 10.1097/00004714-199508000-00014 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA RM826 UT WOS:A1995RM82600014 PM 7593718 ER PT J AU MCCANN, UD RICAURTE, GA AF MCCANN, UD RICAURTE, GA TI ON THE NEUROTOXICITY OF MDMA AND RELATED AMPHETAMINE DERIVATIVES SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID PANIC DISORDER; ECSTASY; FENFLURAMINE C1 JOHNS HOPKINS MED INST,JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD 21205. RP MCCANN, UD (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1995 VL 15 IS 4 BP 295 EP 296 DI 10.1097/00004714-199508000-00017 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA RM826 UT WOS:A1995RM82600017 ER PT J AU ROTH, MJ STERN, JB HAUPT, HM SMITH, RRL BERLIN, SJ AF ROTH, MJ STERN, JB HAUPT, HM SMITH, RRL BERLIN, SJ TI BASAL-CELL CARCINOMA OF THE SOLE SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article AB Basal cell carcinoma (BCC) of the plantar surface of the foot is rare, with only 22 previously reported cases. This clinicopathologic study is based on 20 cases of BCC of the plantar surface and plantar-like surfaces from adjacent lower lateral and medial aspects of the foot, submitted to a large pediatric laboratory from 1986 through June 1992 (total specimens for this period = 518,624; total BCC of lower extremities, below knee = 53). There were 15 women and 5 men. The average patient age was 73 years, with a range from 52 to 92 years. The duration of the lesion before diagnosis was 2 months to 12 years, with an average of 2 years. Three patients had a history of trauma. Pediatric clinical diagnoses included BCC (4), SCC (3), soft tissue tumor (2), nevus (1), granuloma (1), keratosis (2), verucca (1), and psoriasis (1). Follow-up information was available on 10 patients; all were free of disease up to 64 months, with an average follow-up of 15.7 months. Three of 20 BCC showed predominant histologic patterns characteristic of fibroepithelioma,of Pinkus (FEP). An additional three BCC showed focal or suggestive patterns of FEP. Fourteen tumors showed ordinary BCC histologic patterns. No multicentric-superficial or morphea like BCC were observed. The relatively high incidence of FEP in BCC of the sole correlates with abundant sweat glands and lack of hair follicles on the plantar surface, in accordance with the recent proposal that FEP derives its histologic pattern from the spread of BCC do cvn eccrine ducts, eventually replacing them with solid strands of tumor. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. PENN HOSP,PHILADELPHIA,PA. MARYLAND MED METPATH,BALTIMORE,MD. PODIAT PATHOL LABS,BALTIMORE,MD. NR 25 TC 14 Z9 14 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD AUG PY 1995 VL 22 IS 4 BP 349 EP 353 DI 10.1111/j.1600-0560.1995.tb01418.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA RV577 UT WOS:A1995RV57700008 PM 7499575 ER PT J AU BARKSDALE, SK STERN, JB HAUPT, HM MULTHAUPT, H AF BARKSDALE, SK STERN, JB HAUPT, HM MULTHAUPT, H TI PROLIFERATIVE ACTIVITY IN METASTATIC MALIGNANT-MELANOMA - COMPARISON OF PRETREATMENT AND POSTTREATMENT METASTASES SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID NUCLEOLAR ORGANIZER REGIONS; MELANOCYTIC LESIONS; MONOCLONAL-ANTIBODY; LH-RH; BENIGN; AGNORS; PCNA; SOMATOSTATIN; COMBINATION; COUNTS AB In this study, the proliferative activity of malignant melanoma metastases was assessed before and after isolated limb perfusion chemotherapy by quantitating AgNORs, mitoses and PCNA activity. No significant difference in either AgNOR count, mitotic activity or PCNA index was observed. We conclude that AgNOR count, mitotic activity and PCNA index were not significantly effected by isolated limb perfusion chemotherapy. C1 PENN HOSP,DEPT PATHOL,PHILADELPHIA,PA 19107. RP BARKSDALE, SK (reprint author), NIH,PATHOL LAB,BLDG 411,C111,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD AUG PY 1995 VL 22 IS 4 BP 354 EP 358 DI 10.1111/j.1600-0560.1995.tb01419.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA RV577 UT WOS:A1995RV57700009 PM 7499576 ER PT J AU FALK, LA MCNALLY, R PERERA, PY KENNY, J VOGEL, SN AF FALK, LA MCNALLY, R PERERA, PY KENNY, J VOGEL, SN TI LPS-INDUCIBLE RESPONSES IN SEVERE COMBINED IMMUNODEFICIENCY (SCID) MICE SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID GAMMA-INTERFERON-PRODUCTION; EARLY ENDOTOXIN TOLERANCE; MACROPHAGE ACTIVATION; NECROSIS-FACTOR; IFN-GAMMA; LIPID-A; T-CELL; LIPOPOLYSACCHARIDE; PROLIFERATION; STIMULATION AB Lipopolysaccharide (LPS) is a potent bacterial product that has been shown to act on many different cell types both in vivo and in vitro, Injection of immunologically competent mice with LPS results in increased serum cytokine levels, followed by an array of pathophysiologic alterations that can ultimately lead to death, In this study, we examined the response of severe combined immunodeficient (SCID) mice to LPS, These mice lack mature T and B cells and have been shown to be an important model for analyzing the contribution of innate immune responses to infectious agents, Injection of SCID mice with LPS resulted in increases in CSF, TNF, and IFN levels in serum that were similar to the responses of immunocompetent controls, In response to LPS, both SCID and control mice exhibited similar levels of hypoglycemia, LPS-induced toxicity was assessed in D(+)-galactosamine-sensitized animals, SCID mice were comparably sensitive to the lethal effects of LPS as control BALB/c mice. To assess the role of natural killer (NK) cells in LPS-induced cytokine responses, BALB/c and SCID mice were injected with anti-asialo-GM1 antibody prior to injection of LPS, No significant effect on LPS-induced CSF or blood glucose levels were seen, although NK-depleted SCID mice produced somewhat more IFN in response to LPS than normal mice. Thus, NK cells are not a major source of these early LPS-induced cytokines, These data suggest that mature T and B cells and NK cells do not contribute to the initial wave of cytokines produced in response to LPS, but may contribute as secondary producers of cytokines involved in the cytokine cascade elicited by LPS injection. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. US FDA,DIV HEMATOL PROD,BETHESDA,MD 20014. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. NR 43 TC 6 Z9 6 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PD AUG PY 1995 VL 2 IS 4 BP 273 EP 280 PG 8 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA RX432 UT WOS:A1995RX43200007 ER PT J AU BAIN, RL NYBERG, LM AF BAIN, RL NYBERG, LM TI FUNDING FOR UROLITHIASIS RESEARCH - PROGRESS AND STRATEGIES FOR FUTURE NIH SUPPORT SO JOURNAL OF ENDOUROLOGY LA English DT Article AB A review of the National Institutes of Health funding history for urolithiasis shows that support has increased from about $3 million in 1990 to about $4.7 million in 1993 and to an estimated $5.1 million in 1994. The award of large project grants accounts for the increase: individual research project grant funding (R01-type grants) has not increased, The overall funding for urologic research supported by the National Institute of Diabetes and Digestive and Kidney Diseases has more than doubled in this same period, with most of the increase attributable to the award of individual research grants. Although there has been a significant number of urolithiasis research grant applications submitted in this time period, the percent of successful (funded) applications continues to lag behind the number in other urology-related areas, Strategies for improving the award rate for urolithiasis-related research grant applications are reviewed. RP BAIN, RL (reprint author), NIDDK,KUH,DIV KIDNEY UROL & HEMATOL DIS,UROL PROGRAM,NATCHER BLDG,ROOM 6AS-19B,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD AUG PY 1995 VL 9 IS 4 BP 299 EP 300 DI 10.1089/end.1995.9.299 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA RT912 UT WOS:A1995RT91200001 PM 8535455 ER PT J AU GOLDING, EM TEAGUE, WE DOBSON, GP AF GOLDING, EM TEAGUE, WE DOBSON, GP TI ADJUSTMENT OF K' TO VARYING PH AND PMG FOR THE CREATINE-KINASE, ADENYLATE KINASE AND ATP HYDROLYSIS EQUILIBRIA PERMITTING QUANTITATIVE BIOENERGETIC ASSESSMENT SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE CREATINE KINASE; ATP HYDROLYSIS; ADENYLATE KINASE; BIOENERGETICS; METABOLISM; THERMODYNAMICS; FREE MAGNESIUM; PH ID NUCLEAR-MAGNETIC-RESONANCE; OXIDATIVE-PHOSPHORYLATION; RAT-HEART; P-31 NMR; METABOLISM; MUSCLE; SPECTROSCOPY; MYOCARDIUM; TISSUE AB Physiologists and biochemists frequently ignore the importance of adjusting equilibrium constants to the ionic conditions of the cell prior to calculating a number of bioenergetic and kinetic parameters, The present study examines the effect of pH and free magnesium levels (free [Mg2+]) on the apparent equilibrium constants (K') of creatine kinase (ATP: creatine N-phosphotransferase; EC 2.7.3.2), adenylate kinase (ATP:AMP phosphotransferase; EC 2.7.4.3) and adenosinetriphosphatase (ATP phosphohydrolase; EC 3.6.1.3) reactions, We show how K' can be calculated using the equilibrium constant of a specified chemical reaction (K-ref) and the appropriate acid-dissociation and Mg2+-binding constants at an ionic strength (I) of 0.25 mol l(-1) and 38 degrees C, Substituting the experimentally determined intracellular pH and free [Mg2+] into the equation containing a known K-ref and two variables, pH and free [Mg2+], enables K' to be calculated at the experimental ionic conditions, Knowledge of K' permits calculation of cytosolic phosphorylation ratio ([ATP]/[ADP][P-i]), cytosolic free [ADP], free [AMP], standard transformed Gibbs energy of formation (Delta(f)G'degrees(ATP)) and the transformed Gibbs energy of the system (Delta(f)G'(ATP)) for the biological system, Such information is vital for the quantification of organ and tissue bioenergetics under physiological and pathophysiological conditions. C1 JAMES COOK UNIV N QUEENSLAND,DEPT MOLEC SCI,DIV BIOCHEM & HUMAN PHYSIOL,TOWNSVILLE,QLD 4811,AUSTRALIA. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 35 TC 88 Z9 89 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD AUG PY 1995 VL 198 IS 8 BP 1775 EP 1782 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA RM224 UT WOS:A1995RM22400015 PM 7636446 ER PT J AU MASON, LH ORTALDO, JR YOUNG, HA KUMAR, V BENNETT, M ANDERSON, SK AF MASON, LH ORTALDO, JR YOUNG, HA KUMAR, V BENNETT, M ANDERSON, SK TI CLONING AND FUNCTIONAL-CHARACTERISTICS OF MURINE LARGE GRANULAR LYMPHOCYTE-1 - A MEMBER OF THE LY-49 GENE FAMILY (LY-49G2) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; MONOCLONAL-ANTIBODIES; ANTIGEN EXPRESSION; MOLECULAR-CLONING; MHC ANTIGENS; MOUSE NKR-P1; SUSCEPTIBILITY; SENSITIVITY; RESISTANCE AB Large granular lymphocyte (LGL) 1 is a cell surface glycoprotein expressed on a subset (50%) of C57BL/6 natural killer (NK) cells. Immunoprecipitation experiments reveal that the LGL-1 protein exists as a disulfide-linked 40-kD homodimer. Functional studies of LGL-1(+) cells indicate that selected H-2(d) target cells are not lysed efficiently by these interleukin (IL)-2-cultured NK cells. These findings suggested that LGL-1 may be a member of the Ly-49 gene family. Here we report the molecular cloning of the LGL-1 cDNA from a severe combined immunodeficient-adherent lymphokine-activated killer cell library transfected into Cos-7 cells and find LGL-1 to be homologous to the Ly-49 gene at both the nucleotide (85%) and amino acid levels (73%). Sequencing of our LGL-1 cDNA has revealed it to be nearly identical to the Ly-49G2 cDNA recently isolated by cross-hybridization with an Ly-49 probe. LGL-1 represents a type II transmembrane protein of 267 amino acids with its carboxyl end exposed extracellularly. The LGL-1 protein contains 11 highly conserved cysteine residues and a 25-amino acid transmembrane region. Southern blot analysis demonstrates that there are a number of homologous genes in mouse DNA that hybridize strongly to LGL-1. Northern analyses using poly A(+) RNA from LGL-1(+) NK cells indicate that LGL-1 is expressed as a 1.4 kb mRNA. Two-color how cytometry analysis (FCA) of C57BL/6 splenic NK cells demonstrates that LGL-1 and Ly-49 label overlapping subsets of cells. FCA identifies four subsets of NK cells as defined by LGL-1 versus Ly-49 staining. We have sorted these individual subsets, expanded them in IL-2, and performed cytotoxicity experiments to determine their target cell profiles in relation to class I expression. Results of these studies are complex, but indicate that Ly-49 may not be the only molecule that recognizes class I as an inhibitory signal for cytotoxicity. LGL-1(+) cells also fail to lyse several H-2(d)-expressing tumor targets and concanavalin A lymphoblasts from BALB/c but not C57BL/6 mice. This inhibition of lysis by LGL-1(+) NK cells is negated by addition of monoclonal antibody (mAb) 4D11 that recognizes the LGL-1 protein. When mAbs to the class I molecules H-2D(d) and H-2L(d) (alpha(1) alpha(2) domains only) are added to cytotoxicity assays, LGL-1(+) cells lyse H-2(d) targets very effectively. Therefore, LGL-1 recognizes regions of the class I-specific molecules H-2D(d) and H-2L(d). This specificity distinguishes LGL-1 from Ly-49, whose killing was only reversed by antibodies to H-2D(d). The differential specificities recognized by LGL-1 versus Ly-49 support the hypothesis that this family of genes recognizes diverse class I molecules and regulates the lytic activity of NK cells. C1 NCI,FREDERICK CANC RES & DEV CTR,DCT,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. RP MASON, LH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 560,FREDERICK,MD 21702, USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-74101] NR 31 TC 210 Z9 210 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 AUG 1 PY 1995 VL 182 IS 2 BP 293 EP 303 DI 10.1084/jem.182.2.293 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RL098 UT WOS:A1995RL09800005 PM 7629495 ER PT J AU CHEN, T BELLAND, RJ WILSON, J SWANSON, J AF CHEN, T BELLAND, RJ WILSON, J SWANSON, J TI ADHERENCE OF PILUS(-) OPA(+) GONOCOCCI TO EPITHELIAL-CELLS IN-VITRO INVOLVES HEPARAN-SULFATE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; HUMAN FALLOPIAN-TUBES; TISSUE-CULTURE CELLS; HERPES-SIMPLEX VIRUS; MEMBRANE PROTEIN-II; NEISSERIA-GONORRHOEAE; SURFACE RECEPTORS; BORDETELLA-PERTUSSIS; GLYCOPROTEIN-D; ORGAN-CULTURE AB Neisseria gonorrhoeae attaches to host epithelial cells via pill and opacity-associated (Opa) outer membrane proteins. Pilus(-) gonococci (Gc) of strain MS11 adhere to both human and nonhuman cells, but only when particular Cpa proteins are expressed; OpaA(+) variants adhere best, OpaC(+) Variants are next best, and the seven other Opa(+) variants adhere poorly or not at all. The adherence of OpaA(+) Gc to Chinese hamster ovary (CHO) cells is inhibited by heparin or heparan sulfate (HS), but not by chondroitin sulfate. OpaA(+) Gc do not adhere to CHO cells devoid of HS proteoglycans; low concentrations of heparin restore OpaA(+) Gc adherence to these HS-deficient CHO cells and high concentrations inhibit it. H-3-heparin binding to whole Gc parallels their adherence abilities (OpaA(+) > OpaC(+) > OpaH(+) >> Opas B, D, E, F, G, I = Opa(-) = 0). Cpa proteins separated by SDS-PAGE also bind H-3-heparin. These data suggest that adherence of pilus(-), Opa(+) Gc involves HS-proteoglycan of eukaryotic cells. C1 NIAID,ROCKY MT LAB,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. NR 53 TC 127 Z9 127 U1 1 U2 7 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 AUG 1 PY 1995 VL 182 IS 2 BP 511 EP 517 DI 10.1084/jem.182.2.511 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RL098 UT WOS:A1995RL09800026 PM 7629509 ER PT J AU RYAN, JJ KINZER, CA PAUL, WE AF RYAN, JJ KINZER, CA PAUL, WE TI MAST-CELLS LACKING THE HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTOR ARE DEFICIENT IN FC-EPSILON-RI-GAMMA MESSENGER-RNA SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EPIDERMAL LANGERHANS CELLS; IGE RECEPTOR; EXPRESSION; SUBUNIT; CD3-ZETA; FAMILY; CHAIN; GENE AB A population of cells that express mast cell markers, including the membrane protein p161, but that lack expression of the high affinity IgE receptor, Fc epsilon RI, can be routinely grown from bone marrow. Ionomycin, but not IgE immune complexes, causes these cells to release serotonin and to express IL-3 and IL-13 mRNA, consistent with their being FC epsilon RI-deficient mast cells. These p161(+)/Fc epsilon RI(-) mast cells expressed normal amounts of Fc epsilon RI alpha and beta chain mRNA, but extremely low levels of Fc epsilon RI gamma chain mRNA. In addition, this novel mast cell population expressed CD33. chain mRNA, which p161(+)/Fc epsilon RI(+) mast cells did not. CD3 zeta stable transfectants of Abelson-murine leukemia virus-transformed p161(+)/Fc epsilon RI(+) mast cells continued to express Fc epsilon RI. This strongly suggests that the failure of p161(+)/Fc epsilon RI(-) mast cells to express IgE receptors was not caused by the presence of CD3 zeta chain. Transfection of human Fc epsilon RI gamma cDNA into p161(+)/Fc epsilon RI(-) mast cells rescued IgE binding. These stable transfectants released serotonin in response to cross-linkage of Fc epsilon RI, demonstrating that the molecular defect of p161(+)/Fc epsilon RI(-) mast cells is indeed the loss of Fc epsilon RI gamma expression. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 24 TC 12 Z9 12 U1 0 U2 0 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 AUG 1 PY 1995 VL 182 IS 2 BP 567 EP 574 DI 10.1084/jem.182.2.567 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RL098 UT WOS:A1995RL09800032 PM 7629513 ER PT J AU KINZER, CA KEEGAN, AD PAUL, WE AF KINZER, CA KEEGAN, AD PAUL, WE TI IDENTIFICATION OF FC-EPSILON-RI(NEG) MAST-CELLS IN MOUSE BONE-MARROW CELL-CULTURES - USE OF A MONOCLONAL ANTI-P161 ANTIBODY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID RECEPTOR; IGE AB A monoclonal hamster antibody (K-1) specific for a 161-kD mast cell surface glycoprotein was derived. p161 is expressed on normal and cultured mast cells and on some macrophages, but not on basophils or other hematopoietic cells. A population of Fc epsilon R(neg) cells expressing p161 was found in short term cultures of bone marrow cells grown in interleukin (IL)-3. These cells were purified and propagated for extended periods in IL-3. They express c-kit and Fc gamma RII/III, contain alcian blue-positive granules and histamine, and secrete IL-3 in response to ionomycin treatment. Their morphology is consistent with that of mast cells. We propose that they represent Fc epsilon RI(neg) mast cells that can be detected and purified because of their p161 expression. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 11 TC 18 Z9 18 U1 0 U2 0 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 AUG 1 PY 1995 VL 182 IS 2 BP 575 EP 579 DI 10.1084/jem.182.2.575 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RL098 UT WOS:A1995RL09800033 PM 7629514 ER PT J AU KORALNIK, IJ MULLOY, JC ANDRESSON, T FULLEN, J FRANCHINI, G AF KORALNIK, IJ MULLOY, JC ANDRESSON, T FULLEN, J FRANCHINI, G TI MAPPING OF THE INTERMOLECULAR ASSOCIATION OF THE HUMAN T-CELL LEUKAEMIA/LYMPHOTROPIC VIRUS TYPE-I P12(I) AND THE VACUOLAR H+-ATPASE 16 KDA SUBUNIT PROTEIN SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PAPILLOMAVIRUS-E5 TRANSFORMING PROTEIN; LEUKEMIA-LYMPHOMA VIRUS; PORE-FORMING PROTEIN; E5 ONCOPROTEIN; BOVINE PAPILLOMAVIRUS; HTLV-I; TRANSCRIPTIONAL ACTIVATOR; HUMAN RETROVIRUS; TYROSINE KINASE AB The p12(I) protein, a small hydrophobic protein encoded by the human T cell leukaemia/lymphotropic virus type I pX region, contains a proline-rich region located between two putative transmembrane (TM) domains. The p12(I) protein is associated with cellular endomembranes, and physically binds to the 16 kDa subunit of the vacuolar H+-ATPase proton pump. To investigate the nature of the 16 kDa and p12(I) interaction and to determine the oncogenic domain of p12(I), we constructed p12(I) mutant proteins in which various portions of the TM domains were deleted, as well as a p12(I) mutant containing a single amino acid substitution. These mutants were tested for binding to the 16 kDa subunit of the vacuolar H+-ATPase in HeLa/Tat cells and for the capability to potentiate transformation by bovine papillomavirus type 1 E5 oncoprotein in mouse C127 cells. The results indicated that both TM domains of the p12(I) protein were dispensable for its interaction with the 16 kDa protein, whereas partial or complete deletion of the proline-rich region resulted in decreased or no binding of the p12(I) protein to the 16 kDa subunit. Immunofluorescence analysis of HeLa/Tat cells transfected with the p12(I) mutants showed that deletion of the proline-rich region did not alter the subcellular localization of these mutant p12(I) proteins, suggesting direct involvement of the proline-rich domain in binding rather than the failure of these p12(I) mutants to reach the appropriate cellular compartment. Mapping of 16 kDa subunit mutants in binding with the p12(I) protein suggested that molecular determinants located between the second and third TM domain of the 16 kDa protein might be involved in this interaction. Finally, most of the p12(I) mutants lost the ability to potentiate transformation of C127 cells indicating that binding of p12(I) to the 16 kDa subunit does not directly correlate with oncogenicity. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT PATHOL,WASHINGTON,DC 20007. NR 41 TC 32 Z9 34 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1995 VL 76 BP 1909 EP 1916 DI 10.1099/0022-1317-76-8-1909 PN 8 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA RN950 UT WOS:A1995RN95000004 PM 7636472 ER PT J AU MARTINEZ, A MILLER, MJ QUINN, K UNSWORTH, EJ EBINA, M CUTTITTA, F AF MARTINEZ, A MILLER, MJ QUINN, K UNSWORTH, EJ EBINA, M CUTTITTA, F TI NONRADIOACTIVE LOCALIZATION OF NUCLEIC-ACIDS BY DIRECT IN-SITU PCR AND IN-SITU RT-PCR IN PARAFFIN-EMBEDDED SECTIONS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE IN SITU PCR; IN SITU RT-PCR; P53; IGF-1A; TRANSFERRIN; TUMOR CELL LINES; LUNG TUMORS ID POLYMERASE CHAIN-REACTION; IN-SITU; TISSUE-SECTIONS; DNA; EXPRESSION; HYBRIDIZATION; GENE AB Technological developments have made possible extension of polymerase chain reaction (PCR) analysis to individual cells to localize DNA/RNA with non-radioactive labels at the light microscopic level, This approach, in situ PCR, is particularly useful in resolving low-frequency message expression in mixed populations of cells and tissues, We have established a working protocol for direct in situ PCR and have utilized several controls to validate our results, In this report we outline the procedures for detecting either DNA or RNA in a rapid and reproducible manner, We evaluate the sequential steps required for this analysis, such as protease hydrolysis, DNAse digestion, ''hot start'' capabilities, and detection methods, We have applied these methods in several applications, including detection of the p53 gene in human tumor samples, localization of insulin-like growth factor-IA mRNA in cell lines with low levels of expression, and distribution of transferrin mRNA in lung cancer cell lines and tumors, We demonstrate from this study that the in situ PCR technique is an investigative approach capable of detecting specific DNA/RNA sequences at the cellular level and of identifying cells with low levels of mRNA expression. RP MARTINEZ, A (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,ROCKVILLE,MD 20850, USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 34 TC 61 Z9 63 U1 0 U2 3 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 1995 VL 43 IS 8 BP 739 EP 747 PG 9 WC Cell Biology SC Cell Biology GA RL823 UT WOS:A1995RL82300001 PM 7542678 ER PT J AU XU, LL BADOLATO, R MURPHY, WJ LONGO, DL ANVER, M HALE, S OPPENHEIM, JJ WANG, JM AF XU, LL BADOLATO, R MURPHY, WJ LONGO, DL ANVER, M HALE, S OPPENHEIM, JJ WANG, JM TI A NOVEL BIOLOGIC FUNCTION OF SERUM AMYLOID-A - INDUCTION OF T-LYMPHOCYTE MIGRATION AND ADHESION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; A PROTEIN; RECEPTORS; IDENTIFICATION; NEUTROPHILS; DEGRADATION; MONOCYTES; SAA AB In the course of an inflammatory response, the concentration of serum amyloid A (SAA), a hepatocyte-derived acute phase protein, increases up to 1000-fold above the normal level, Although SAA was previously thought to be immunosuppressive, we recently reported that SAA is a potent chemoattractant for monocytes and neutrophils. The present study shows that recombinant human (rh) SAA also induces directional migration oi T cells in vitro. Phenotypic analyses revealed that CD4(+) and CD8(+) T cell subsets were equally responsive to rhSAA, whereas CD45RA cells were also not selectively attracted by rhSAA. The T cell chemotaxis induced by rhSAA was inhibited by pretreatment of cells with pertussis toxin, suggesting the interaction of rhSAA with a G-protein-coupled receptor species. T cells pretreated with an optimal concentration of SAA exhibited enhanced adherence to human umbilical cord endothelial cell monolayers. Subcutaneous administration of rhSAA into huPBL-SCID mice caused the infiltration oi human T lymphocytes at the injection sites by 4 h. These results suggest that SAA may play an important role in recruiting T lymphocytes, as well as neutrophils and monocytes into inflammatory lesions. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RI Badolato, Raffaele/A-8081-2010 OI Badolato, Raffaele/0000-0001-7375-5410 NR 27 TC 134 Z9 137 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1995 VL 155 IS 3 BP 1184 EP 1190 PG 7 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800020 PM 7636186 ER PT J AU GARRAUD, O NKENFOU, C BRADLEY, JE PERLER, FB NUTMAN, TB AF GARRAUD, O NKENFOU, C BRADLEY, JE PERLER, FB NUTMAN, TB TI IDENTIFICATION OF RECOMBINANT FILARIAL PROTEINS CAPABLE OF INDUCING POLYCLONAL AND ANTIGEN-SPECIFIC IGE AND IGG4 ANTIBODIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN HELMINTH INFECTIONS; IMMUNOGLOBULIN PRODUCTION; ONCHOCERCA-VOLVULUS; TH2 CLONES; IFN-GAMMA; CELLS; POPULATIONS; LYMPHOCYTES; RESPONSES; IL-4 AB Filarial infection is characterized by an immune response associated with the production of Ag-specific IgG4 and IgE and IL-4 and IL-5. To identify filarial Ags capable of inducing such responses and to analyze the role Ags themselves play in sustaining it, 24 recombinant filarial parasite proteins were screened for their ability to be recognized by sera from 67 individuals with tissue-invasive filarial infections. Among the recombinant proteins that were recognized by IgG4 or IgE Abs in 25% of the sera or more, two were selected on the basis of their ability to elicit polyclonal and Ag-specific IgE/IgG4 Abs in vitro. Ov27 (analogous to Ov7/cystatin, a cysteine protease inhibitor) and OvD5B (analogous to Ov33, an aspartyl protease inhibitor) induced both a polyclonal and Ag-specific IgE/IgG4 response that was blocked by neutralizing Abs to IL-4 and to IL-13 or by soluble IL-4 receptors. Recombinant human IFN-gamma and IL-12 also led to a decrease in the production of polyclonal and Ag-specific IgE/IgG4 Abs. In addition, these two recombinant proteins preferentially stimulated the secretion of IL-4, IL-5, and IL-10 (in contrast to IFN-gamma). The data suggest that certain epitopes on filarial Ags preferentially elicit a Th2-type response and provide an in vitro model for dissecting the mechanisms underlying this preferential response. C1 UNIV YAOUNDE,IMMUNOL BIOTECHNOL LAB,YAOUNDE,CAMEROON. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,LONDON,ENGLAND. NEW ENGLAND BIOLABS INC,BEVERLY,MA 01915. RP GARRAUD, O (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Bradley, Janette/0000-0003-3973-7977 NR 54 TC 70 Z9 73 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 AUG 1 PY 1995 VL 155 IS 3 BP 1316 EP 1325 PG 10 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800033 PM 7543519 ER PT J AU KANG, XQ KAWAKAMI, Y ELGAMIL, M WANG, RF SAKAGUCHI, K YANNELLI, JR APPELLA, E ROSENBERG, SA ROBBINS, PF AF KANG, XQ KAWAKAMI, Y ELGAMIL, M WANG, RF SAKAGUCHI, K YANNELLI, JR APPELLA, E ROSENBERG, SA ROBBINS, PF TI IDENTIFICATION OF A TYROSINASE EPITOPE RECOGNIZED BY HLA-A24-RESTRICTED, TUMOR-INFILTRATING LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; METASTATIC MELANOMA; AUTOLOGOUS MELANOMA; IMMUNOTHERAPY; CDNA AB A number of Ags recognized by class I-restricted, melanoma-specific T cells have recently been identified. In this report we demonstrated that tumor-infiltrating lymphocytes (TIL) from melanoma patient 1413 recognize a tumor Ag, tyrosinase, in the context of HLA-A24. This Ag had previously been shown to be recognized by an HFA-A24-restricted TIL, TIL 888, as well as HLA-A2-restricted, melanoma-specific T cells isolated from two additional patients. The peptide epitope recognized by TIL 1413 was then identified through the use of sequential deletions of the tyrosinase cDNA, as well as through prediction of HLA-A24 binding peptides based on a previously identified motif. Two peptides, a 9-amino acid peptide (AFLPWHRLF) and an overlapping 10-amino acid peptide (AFLPWHRLFL) containing an additional leucine at the carboxyl terminus, were both recognized by TIL 1413. Anti-peptide-specific CTL could be induced by repeated stimulation of peripheral blood lymphocytes from melanoma patient 1413, and this CTL line specifically recognized both HLA-A24(+) B cell lines pulsed with the peptide and HLA-A24(+) tyrosinase(+) melanoma cells. This peptide thus represents a reagent that may be used to generate melanoma-specific T cells for adoptive immunotherapy, as well as in peptide vaccines for HLA-A24(+) melanoma patients. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP KANG, XQ (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 27 TC 139 Z9 140 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 AUG 1 PY 1995 VL 155 IS 3 BP 1343 EP 1348 PG 6 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800036 PM 7543520 ER PT J AU BOSCO, MC PULKKI, K ROWE, TK ZEA, AH MUSSO, T LONGO, DL VARESIO, L ESPINOZADELGADO, I AF BOSCO, MC PULKKI, K ROWE, TK ZEA, AH MUSSO, T LONGO, DL VARESIO, L ESPINOZADELGADO, I TI IL-4 INHIBITS IL-2-INDUCED TUMORICIDAL ACTIVITY AND SECRETORY FUNCTIONS OF HUMAN MONOCYTES - MODULATION OF IL-2 BINDING AND IL-2 RECEPTOR BETA-GAMMA CHAIN EXPRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATED HUMAN-MONOCYTES; NECROSIS FACTOR-ALPHA; INTERLEUKIN-2 RECEPTOR; IFN-GAMMA; GENE-EXPRESSION; MESSENGER-RNA; KILLER CELLS; B-CELLS; PROLIFERATION; LYMPHOKINE AB Human monocytes express functional IL-2 receptors (IL-2R) and are directly activated by IL-2 to exert effector and secretory functions. In this study, we show that IL-4 selectively suppressed, in a dose-dependent manner, IL-2-induced monocyte tumoricidal activity, without affecting IFN-gamma-dependent cytotoxicity. This effect was specific because a neutralizing anti-IL-4 mAb completely restored IL-2-activated cytolysis. Furthermore, IL-4 effectively blocked the secretion of proinflammatory cytokines by IL-2-stimulated monocytes. Binding studies with biotin-conjugated IL-2 demonstrated that monocyte stimulation with IL-2 increased IL-2 binding to the cell surface, and that treatment with IL-4 inhibited this augmentation, providing a possible explanation for the decreased responsiveness of monocytes to IL-2 in the presence of IL-4. However, IL-4 suppressive effects could not be ascribed to the down-regulation of the individual components of the IL-2R complex. In fact, co-treatment of monocytes with IL-2 and IL-4 increased the expression of IL-2R gamma chain above the levels induced by IL-2 alone, whereas it did not significantly affect the expression of IL-2R beta chain. Thus, the inhibition of IL-2 binding by IL-4 may be due to the recruitment of the gamma chain into the IL-4-IL-4R system, making it unavailable for participation in the formation of IL-2 binding sites. These findings provide the first evidence of the ability of IL-4 to suppress IL-2-mediated activation of human monocytes and suggest that IL-4 may play an important role in vivo as an inhibitory signal that controls the response of monocytes to IL-2. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,CLIN RES BRANCH,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. TURKU UNIV,SF-20520 TURKU,FINLAND. NCI,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20832. RP BOSCO, MC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 57 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1995 VL 155 IS 3 BP 1411 EP 1419 PG 9 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800043 PM 7636206 ER PT J AU GAZZINELLI, RT BALA, S STEVENS, R BASELER, M WAHL, L KOVACS, J SHER, A AF GAZZINELLI, RT BALA, S STEVENS, R BASELER, M WAHL, L KOVACS, J SHER, A TI HIV-INFECTION SUPPRESSES TYPE-1 LYMPHOKINE AND IL-12 RESPONSES TO TOXOPLASMA-GONDII BUT FAILS TO INHIBIT THE SYNTHESIS OF OTHER PARASITE-INDUCED MONOKINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; STIMULATORY FACTOR INTERLEUKIN-12; ACTIVATED HUMAN MACROPHAGES; IMMUNE-DEFICIENCY SYNDROME; CD8+ LYMPHOCYTES-T; GAMMA-INTERFERON; FACTOR-ALPHA; MYCOBACTERIUM-TUBERCULOSIS; CEREBRAL TOXOPLASMOSIS AB Individuals infected with Toxoplasma gondii normally develop resistance to the parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this resistance is lost leading to reactivation of infection and development of encephalitis. To characterize the cytokine response of T. gondii-iniected individuals, PBMC were cultured in vitro in the presence or absence of crude tachyzoite Ags (STAg). When stimulated with STAg, PBMC from T.gondii-infected donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and IFN-gamma) as well as the monokine IL-12, in the absence of detectable Type 2 lymphokines (IL-4 and IL-5). In contrast, cells of individuals from both groups produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag preparation. By using highly purified elutriated cells, we demonstrated that monocytes are a major source of these monokines. The above findings were further expanded by analyzing the cytokine responses induced by STAg in PBMC from patients co-infected with T.gondii and HIV. Our results demonstrate that parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before AIDS development, as is IL-12 synthesis by PBMC from HIV-infected individuals stimulated with STAg. In contrast, the release of IL-6 and TNF-alpha triggered by STAg is either not affected or augmented during HIV infection. C1 NIAID,CCM CC,PARASIT DIS LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. US FDA,DAVDP,ROCKVILLE,MD 20857. PRI DYNCORP,FREDERICK,MD 21701. UNIV FED MINAS GERAIS,INST CIENCIAS BIOL,DEPT BIOCHEM & IMMUNOL,BELO HORIZONT,MG,BRAZIL. NR 56 TC 74 Z9 75 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 AUG 1 PY 1995 VL 155 IS 3 BP 1565 EP 1574 PG 10 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800059 PM 7636218 ER PT J AU SUGIHARA, S FUJIWARA, H NIIMI, H SHEARER, GM AF SUGIHARA, S FUJIWARA, H NIIMI, H SHEARER, GM TI SELF-THYROID EPITHELIAL-CELL (TEC)-REACTIVE CD8(+) T-CELL LINES CLONES DERIVED FROM AUTOIMMUNE-THYROIDITIS LESIONS - THEY RECOGNIZE SELF-THYROID ANTIGENS DIRECTLY ON TEC TO EXHIBIT T-HELPER CELL 1-TYPE LYMPHOKINE PRODUCTION AND CYTOTOXICITY AGAINST TEC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PERIPHERAL-BLOOD LYMPHOCYTES; INTERFERON-GAMMA; MONOCLONAL-ANTIBODY; ALLERGIC ENCEPHALOMYELITIS; HUMAN THYROCYTES; MHC MOLECULES; MICE; RECEPTOR; BETA AB Self-thyroid epithelial cell (TEC)-reactive CD8(+) and CD4(+) T cell lines were established by culturing T cells that infiltrate in autoimmune thyroiditis lesions. We investigated the properties of CD8(+) T cell lines and clones in comparison with previously characterized CD4(+) T cell lines/clones. Although the recognition of self-Ag by anti-TEC CD4(+) T cell lines/clones required the cooperation of syngeneic spleen cells as APC, a representative CD8(+) line (N4C) was stimulated with syngeneic TEC in the absence of APC. Precise analysis of MHC restriction using N4C-derived clones revealed that CD8(+) clones recognize self-Ag on TEC in the context of class I MHC molecules. Most CD8(+) clones were also found to express TCR with V beta specificities that were different from those observed for anti-TEC CD4(+) clones. N4C cells produced IL-2, IFN-gamma, and TNF-alpha beta, but not IL-4 and IL-5 after stimulation with TEC, thus exhibiting the profile of lymphokine production similar to that expressed by CD4(+) Th1 on one hand, but on the other, they showed the functional property that has not been observed for anti-TEC CD4+ clones. Namely, they elicited appreciable levels of cytolytic effects on syngeneic TEC in a short-term (4-h) Cr-51 release assay. Thus, these results indicate that self-TEC-reactive CD8(+) T cell lines/clones recognize Ag directly on TEC in a class I MHC-restricted way so as to exhibit various functions including the Th1-like profile of lymphokine production and anti-TEC cytolysis. The results are also discussed in terms of the nature of self-Ag presented with class I MHC molecules on TEC, as well as the potential roles of anti-TEC CD8(+) T cells in the pathogenesis of thyroiditis. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. OSAKA UNIV,SCH MED,BIOMED RES CTR,OSAKA 553,JAPAN. RP SUGIHARA, S (reprint author), CHIBA UNIV,SCH MED,DEPT PEDIAT,CHUO KU,1-8-1 INOHANA,CHIBA 260,JAPAN. NR 68 TC 24 Z9 24 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 AUG 1 PY 1995 VL 155 IS 3 BP 1619 EP 1628 PG 10 WC Immunology SC Immunology GA RK898 UT WOS:A1995RK89800064 PM 7543527 ER PT J AU RUSSO, TA STAPLETON, A WENDEROTH, S HOOTON, TM STAMM, WE AF RUSSO, TA STAPLETON, A WENDEROTH, S HOOTON, TM STAMM, WE TI CHROMOSOMAL RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM ANALYSIS OF ESCHERICHIA-COLI STRAINS CAUSING RECURRENT URINARY-TRACT INFECTIONS IN YOUNG-WOMEN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TRIMETHOPRIM-SULFAMETHOXAZOLE; NATURAL-HISTORY; DOUBLE-BLIND; DIAGNOSIS; CYSTITIS; TRIAL AB To determine whether recurrent, symptomatic urinary tract infections (UTIs) in a given individual are due to the same or different strains, 71 Escherichia coli strains that caused recurrent UTIs were prospectively collected from 23 infection-prone young women and studied by chromosomal restriction fragment length polymorphism (RFLP) analysis using pulsed-field gel electrophoresis. Thirty-five strains from women with first-episode UTIs were also studied. Overall, 30 (68%) of 44 recurrent UTIs were caused by a strain previously identified in that person. In contrast, 32 of 35 strains from first-episode UTIs had unique RFLP profiles. Analysis of a subset of subjects established that the majority of recurrent UTIs were due to reinfection, not persistence of the pathogen within the urinary tract, and suggested that the colonic flora was the reservoir for these reinfecting strains. C1 UNIV WASHINGTON, DEPT MED, SEATTLE, WA USA. NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. RP RUSSO, TA (reprint author), SUNY BUFFALO, CTR CLIN, DEPT MED, ROOM BB132, 462 GRIDER ST, BUFFALO, NY 14215 USA. RI Stapleton, Ann/N-2428-2015 OI Stapleton, Ann/0000-0003-0130-8659 FU NIAID NIH HHS [AI-01115] NR 23 TC 106 Z9 107 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1995 VL 172 IS 2 BP 440 EP 445 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RK464 UT WOS:A1995RK46400016 PM 7622887 ER PT J AU MCCARTHY, JS GUINEA, A WEIL, GJ OTTESEN, EA AF MCCARTHY, JS GUINEA, A WEIL, GJ OTTESEN, EA TI CLEARANCE OF CIRCULATING FILARIAL ANTIGEN AS A MEASURE OF THE MACROFILARICIDAL ACTIVITY OF DIETHYLCARBAMAZINE IN WUCHERERIA-BANCROFTI INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PARASITE ANTIGENEMIA; ENDEMIC FILARIASIS; PACIFIC ISLAND; IGG4; DIAGNOSIS; IVERMECTIN; ANTIBODIES; ASSAY; IGE AB Small doses of diethylcarbamazine (DEC) clear microfilariae (MF) from the blood of Wuchereria bancrofti-infected persons, but the dose and regimen required to kill adult worms is not clearly defined. A prospective study was undertaken to examine the macrofilaricidal effect of DEC and the ability of an assay for circulating filarial antigen (CFA) to define the effect. Twenty-five MF-positive subjects and 7 MF-negative but CFA-positive subjects were treated with DEC and followed for 18 months. Of the 25 MF-positive patients, 24 cleared MF, and 22 of 26 CFA-positive subjects cleared CFA. A significantly greater decrease in antifilarial IgG4 was seen in patients who cleared CFA than in those who did not. The complete clearance of CFA observed after therapy with DEC indicates that assessment of CFA clearance is a useful means for detecting macrofilaricidal effects of antifilarial chemotherapy. C1 DEPT HLTH,MAUKE,COOK ISLANDS. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. RP MCCARTHY, JS (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 23 TC 53 Z9 54 U1 1 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 AUG PY 1995 VL 172 IS 2 BP 521 EP 526 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RK464 UT WOS:A1995RK46400026 PM 7622896 ER PT J AU PARDI, D COLIGAN, JE LAL, RB AF PARDI, D COLIGAN, JE LAL, RB TI MAPPING OF LINEAR EPITOPES OF THE REGULATORY PROTEINS OF HUMAN T-CELL LYMPHOTROPIC VIRUS (HTLV) TYPE-II - IDENTIFICATION OF AN HTLV-IIB-RESTRICTED EPITOPE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID SUBTYPE-B AB Epitope mapping analyses using synthetic peptides representing the RexII and TaxII proteins identified predominant seroreactivity to the carboxyl terminus of the HTLV-IIG12 TaxII protein (G12Tax 22-G12Tax24, amino acids [aa] 312-356). Moderate reactivity to only 1 RexII peptide (G12Rex9, aa 121-140) was found, while all other RexII and TaxII peptides exhibited minimal reactivity. Peptide G12Tax24 (aa 337-356) corresponded to the extended portion of the TaxII protein characteristic of HTLV-IIb viruses and appeared to represent an HTLV-IIb-restricted epitope. This study showed that this peptide can be used in immunoassays as a quick, simple serologic tool for assessing the minimal number of HTLV-IIb viruses present within specific populations, especially when genomic DNA is not available. C1 NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. RP PARDI, D (reprint author), CTR DIS CONTROL & PREVENT,RETROVIRUS DIS BRANCH,MAIL STOP G-19,1600 CLIFTON RD NE,ATLANTA,GA 30333, USA. NR 13 TC 3 Z9 3 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 AUG PY 1995 VL 172 IS 2 BP 554 EP 557 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RK464 UT WOS:A1995RK46400034 PM 7622904 ER PT J AU MARKUS, NR ROSENBERG, SA TOPALIAN, SL AF MARKUS, NR ROSENBERG, SA TOPALIAN, SL TI ANALYSIS OF CYTOKINE SECRETION BY MELANOMA-SPECIFIC CD4+ T-LYMPHOCYTES SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; AUTOLOGOUS TUMOR; CELL CLONES; APOPTOSIS; RELEASE; GAMMA; CD8+ AB Although specific antitumor immune reactivity has been documented extensively in CD8(+) T cells derived from melanoma patients, relatively little is known about CD4(+) T cell responses against melanoma. Tumorinfiltrating lymphocytes (TIL) cultured from metastatic lesions it five patients yielded cytolytic CD8(+) T cells with specific activity against autologous and MHC class I-compatible allogeneic melanoma targets. In four of the five cases studied, CD4(+) T cells purified from bulk TIL cultures also reacted specifically with autologous melanoma cells, as manifested by the secretion of various cytokines (GM-CSF, TNF-alpha, and IFN-gamma) after a 24 h cocultivation. Cytokine secretion by CD4(+) T cells was MHC class II restricted, and proved to be a more reliable indicator of the immunologic reactivity of CD4(+) T cells than cytolysis. Three of the four reactive CD4(+) TIL failed to recognize allogeneic melanomas, suggesting recognition of Ag with limited expression in the patient population. Cloning such Ags may provide clues to optimizing current antitumor immunization strategies. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NR 23 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 1995 VL 15 IS 8 BP 739 EP 746 DI 10.1089/jir.1995.15.739 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA RP411 UT WOS:A1995RP41100010 PM 8528947 ER PT J AU SCANDURRO, AB WANG, QZ GOODMAN, L LEDBETTER, S DOOLEY, TP YUSPA, SH LICHTI, U AF SCANDURRO, AB WANG, QZ GOODMAN, L LEDBETTER, S DOOLEY, TP YUSPA, SH LICHTI, U TI IMMORTALIZED RAT WHISKER DERMAL PAPILLA CELLS COOPERATE WITH MOUSE IMMATURE HAIR FOLLICLE BUDS TO ACTIVATE TYPE-IV PROCOLLAGENASES IN COLLAGEN MATRIX COCULTURE - CORRELATION WITH ABILITY TO PROMOTE HAIR FOLLICLE DEVELOPMENT IN NUDE-MOUSE GRAFTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE BASIC FIBROBLAST GROWTH FACTOR; TRANSFORMING GROWTH FACTOR; KERATINOCYTE GROWTH FACTOR; ACIDIC FIBROBLAST GROWTH FACTOR ID GROWTH-FACTORS; TISSUE; PROLIFERATION; POPULATIONS; FIBROBLASTS; STROMELYSIN; EXPRESSION AB An in vivo nude mouse graft model and an in vitro collagen matrix culture system were used to study interactions of immature hair follicle buds from new-born mice with clonally derived AdE1A-12S-immortalized rat whisker dermal papilla cell lines, Of the 19 available dermal papilla cell lines, four consistently supported good hair follicle development and hair growth in grafts, Seven cell lines were clearly negative in this assay, and the remaining eight cell lines yielded poor to moderate hair growth, As a correlate to in vivo extracellular matrix remodeling accompanying hair follicle development, type IV collagenase activity in the medium from cocultures of dermal papilla cells and hair follicle buds was analyzed by gelatin zymography, Hair follicle buds cultured alone secrete primarily the 92-kDa type IV procollagenase, Cocultivation of hair follicle buds with eight of the dermal papilla cell lines resulted in activation of this proenzyme and activation of the 72-kDa and 92-kDa type IV procollagenases produced by the dermal papilla cells, Seven of these eight dermal papilla cell lines support hair growth in the graft system, In the absence of dermal papilla cells, several growth factors induced activation of the 92-kDa procollagenase secreted by hair follicle buds cultured in serum-free medium: epidermal growth factor, transforming growth factor alpha, acidic fibroblast growth factor, and keratinocyte growth factor, The current working hypothesis is that a) hair follicle epithelial cells interact with dermal papilla cells in coculture by mutual induction of growth factors and cytokines that stimulate the release and activation of matrix remodeling proteases; and b) the ability of dermal papilla cells to interact with hair follicle epithelial cells in this way may be crucial for controlled dermal matrix remodeling during HF development. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. UPJOHN CO,HAIRGROWTH RES,KALAMAZOO,MI. NR 21 TC 10 Z9 10 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1995 VL 105 IS 2 BP 177 EP 183 DI 10.1111/1523-1747.ep12317089 PG 7 WC Dermatology SC Dermatology GA RM542 UT WOS:A1995RM54200006 PM 7636298 ER PT J AU WALSH, CE MANN, MM EMMONS, RVB WANG, SH LIU, JM AF WALSH, CE MANN, MM EMMONS, RVB WANG, SH LIU, JM TI TRANSDUCTION OF CD34-ENRICHED HUMAN PERIPHERAL AND UMBILICAL-CORD BLOOD PROGENITORS USING A RETROVIRAL VECTOR WITH THE FANCONI-ANEMIA GROUP-C GENE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE TRANSDUCTION; RETROVIRAL VECTOR; ANEMIA; HEMATOPOIESIS; UMBILICAL ID CD34+ MARROW-CELLS; TRANSPLANTATION AB Background: Fanconi anemia (FA) is an autosomal recessive inherited form of bone marrow failure. FA cells are characterized by their extreme sensitivity to DNA cross-linking agents that cause DNA instability and cell death. Four genetic complementation groups for FA have been identified and the gene for the complementation C group (FACC) has been cloned, Genetic transfer of the FACC gene should provide a growth advantage in transduced hematopoietic cells, We have previously demonstrated efficient retroviral-mediated gene transduction and correction of FA(C) cell lines and peripheral blood-derived CD34+ progenitors from patients carrying mutant FACC alleles, In this report we sought to define the optimal conditions for transduction of CD34+ progenitors from mobilized peripheral blood and umbilical cord blood. Methods: Peripheral blood hematopoietic progenitors were obtained by G-CSF mobilization followed by apheresis. Human fetal cord blood cells were obtained from full-term gestation deliveries, Cells were immunoselected for CD34 antigen expression and then incubated with recombinant retroviruses containing a selectable marker gene (neomycin). Recombinant colony stimulating factors were added to facilitate viral transduction. Cells were plated in methylcellulose and resulting hematopoietic colonies were isolated and analyzed by PCR. Results: Transduction efficiency of peripheral blood progenitors (from normal individuals) using a retrovirus encoding the FACC cDNA was comparable to that of the retroviral producer G1Na.40 currently being used in clinical gene therapy marking studies. We extended our standard transduction protocol to analyze CD34+ and CD34+ CD38-subpopulations of progenitors derived from umbilical cord blood (from normal pregnancies). In addition, we tested whether FACC cDNA transduction could be improved by vector infection supported by autologous stroma, For FA(C) hematopoietic cell infection, vector supernatant transduction in the presence of recombinant human IL-3, IL-6, and SCF was found to be superior to transduction supported by autologous FA(C) patient stroma. Conclusions: We documented efficient retroviral transduction of umbilical cord blood and peripheral blood enriched for hematopoietic progenitor cells. These results suggest the feasibility of a clinical gene therapy protocol utilizing progenitor cells from both peripheral blood and umbilical cord blood. C1 GEORGE WASHINGTON UNIV,DEPT OBSTET GYNECOL,DIV MATERNAL FETAL MED,WASHINGTON,DC. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP WALSH, CE (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,SERV HEMATOL,BLDG 10,RM 2C390,BETHESDA,MD 20892, USA. NR 28 TC 13 Z9 13 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Investig. Med. PD AUG PY 1995 VL 43 IS 4 BP 379 EP 385 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA RT746 UT WOS:A1995RT74600007 PM 7552587 ER PT J AU BOERMAN, OC GREGORIO, TA GRZEGORZEWSKI, KJ FALTYNEK, CR KENNY, JJ WILTROUT, RH KOMSCHLIES, KL AF BOERMAN, OC GREGORIO, TA GRZEGORZEWSKI, KJ FALTYNEK, CR KENNY, JJ WILTROUT, RH KOMSCHLIES, KL TI RECOMBINANT HUMAN IL-7 ADMINISTRATION IN MICE AFFECTS COLONY-FORMING UNITS-SPLEEN AND LYMPHOID PRECURSOR CELL LOCALIZATION AND ACCELERATES ENGRAFTMENT OF BONE-MARROW TRANSPLANTS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE HEMATOPOIETIC PRECURSOR MOBILIZATION; LYMPHOID RECONSTITUTION; LYMPHOPOIESIS; MYELOPOIESIS ID GROWTH-PROMOTING ACTIVITY; NECROSIS FACTOR-ALPHA; LONG-TERM CULTURE; T-CELL; THYMOCYTE PROLIFERATION; HUMAN INTERLEUKIN-7; MURINE THYMOCYTES; PROGENITOR CELLS; LYMPHOPOIESIS; PURIFICATION AB Murine reconstitution assays were used to investigate the effects of recombinant human interleukin-7 (rhIL-7) on myeloid and lymphoid precursors and on bone marrow engraftment, Reconstitution with bone marrow from rhIL-7-treated mice results in a 3.4-fold decrease in total colony-forming unit-spleen (CFU-S) activity (day 9) and an 18.1- and 11.9-fold decrease in its ability to generate thymocytes and splenic B lineage cells, respectively, In contrast, after reconstitution with splenocytes from rhIL-7-treated mice, CFU-S activity increased 23.6-fold (day 9) and the thymocyte and splenic B lineage cell regenerative capacity increased by 4.0- and 3.2-fold, respectively, In addition, CD43(low+), B220(low+) cells that contain pre-pro-B cells and pro-B cells were expanded two- to threefold and Ig mu(-), B220(+), CD2(-) and Ig mu(-), B220(+), CD2(+) B lineage cells were expanded approximately 10-fold and 10- to 45-fold (depending on the tissue examined), respectively, after rhIL-7 treatment, Administration of rhIL-7 to irradiated mice transplanted with bone marrow resulted in accelerated T cell and B cell reconstitution by up to 2-4 weeks, Thus, rhIL-7 administration affects the distribution of myeloid and lymphoid precursors, Moreover, rhIL-7 administration accelerates murine bone marrow cell engraftment and therefore may be useful in reducing the engraftment time in bone marrow transplant patients. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD. STERLING WINTHROP INC,COLLEGEVILLE,PA. RI Boerman, Otto/A-8112-2014 OI Boerman, Otto/0000-0001-6832-101X NR 33 TC 20 Z9 21 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 1995 VL 58 IS 2 BP 151 EP 158 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA RP559 UT WOS:A1995RP55900005 PM 7643010 ER PT J AU YE, JP ORTALDO, JR CONLON, K WINKLERPICKETT, R YOUNG, HA AF YE, JP ORTALDO, JR CONLON, K WINKLERPICKETT, R YOUNG, HA TI CELLULAR AND MOLECULAR MECHANISMS OF IFN-GAMMA PRODUCTION INDUCED BY IL-2 AND IL-12 IN A HUMAN NK CELL-LINE SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE IFN-GAMMA; IL-2; IL-12; NK3.3 CELL ID PROTEIN-KINASE-C; NATURAL-KILLER-CELLS; STIMULATORY FACTOR; INTERFERON-GAMMA; INTERLEUKIN-12; ACTIVATION; INDUCTION; GENE; EXPRESSION; INHIBITOR AB Interferon-gamma (IFN-gamma) is an important immunoregulatory protein produced predominantly by T cells and large granular lymphocytes (LGL) in response to different extracellular signals. In particular, two interleukins (ILs), IL-2 and IL-12, have been shown to be potent inducers of IFN-gamma gene expression in both T cells and LGL, Although it has been reported that there are some T cell lines that produce IFN-gamma in response to IL-2 and IL-12 stimulation, there has as yet been no report of a natural killer (NK) cell line that responds in a similar manner, In this report we present evidence that the cell line NK3.3 derived from human NK cells, responds to both IL-2 and IL-12, as measured by increases in IFN-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) cytoplasmic mRNA and protein expression, In addition, when used together IL-2 and IL-12 synergized in the induction of IFN-gamma and GM-CSF and this synergy was attributed to an increased accumulation and stability of the IFN-gamma and GM CSF mRNAs, To investigate the signaling pathways involved in the gene induction, five inhibitors, cyclosporin A (CsA), transforming growth factor-p, cycloheximide, genistein, and staurosporine A, were used in analyzing the effects of IL-2 and IL-12 on NK3.3 cells, The results suggest that activation of protein kinase C, but not new protein synthesis, is required for IL-2 induction of IFN-gamma and GM CSF cytoplasmic mRNA, In contrast, IL-12 induction of IFN-gamma cytoplasmic mRNA appears to only partially depend on activation of protein kinase C, Furthermore, both transforming growth factor-beta and genistein, a tyrosine kinase inhibitor, could suppress IL-2 and IL-12 signaling but CsA was generally inactive, It also was observed that suppression of cytokine gene expression by these agents was independent of the inhibition of proliferation, In addition, IL-2 but not IL-12 induced nuclear factors NF-KB and AP1, and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression, These data indicate that IL-2 and IL-12 may have distinct signaling pathways leading to the induction of IFN-gamma and GM-CSF gene expression, and that the NK3.3 cell line may serve as a novel model for dissecting the biochemical and molecular events involved in these pathways. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NR 42 TC 76 Z9 80 U1 0 U2 2 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 AUG PY 1995 VL 58 IS 2 BP 225 EP 233 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA RP559 UT WOS:A1995RP55900014 PM 7643015 ER PT J AU MASON, AT MCVICAR, DW SMITH, CA YOUNG, HA WARE, CF ORTALDO, JR AF MASON, AT MCVICAR, DW SMITH, CA YOUNG, HA WARE, CF ORTALDO, JR TI REGULATION OF NK CELLS THROUGH THE 80-KDA TNFR (CD120B) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE NK CELLS; TNF RECEPTOR; REGULATION; LAK ACTIVITY; LARGE GRANULAR LYMPHOCYTES ID TUMOR-NECROSIS-FACTOR; NATURAL-KILLER CELLS; FACTOR-ALPHA; T-CELLS; MOLECULAR-CLONING; EMERGING FAMILY; FACTOR RECEPTOR; CYTO-TOXICITY; ACTIVATION; LYMPHOCYTES AB By using monoclonal antibody specific for tumor necrosis factor receptor(80) (TNFR(80)) (CD120b) and TNFR(60) (CD120a), we determined which receptor transduces the signals involved in activating natural killer (NK) cells, Purified CD56(+)CD3(-) large lymphocytes express TNFR(80) but not TNFR(80) and interleukin-2 (IL-2) up-regulates TNFR(80) expression, consistent with NK cells being activated in vivo, Treatment of NK cells with anti-TNFR(80) for 18 h enhanced the NK activity detected on K562 target cells mimicking the effect of TNF, In combination with IL-2, TNF enhanced the development of lymphokine-activated killing. However, only anti-TNFR(80) abrogated IL-2 induction of lymphokine-activated killer cell activity, The activity of TNF or anti-TNFR(80) was selective for NK cytotoxic function because they did not directly mimic IL-2 activation or induce significant proliferation, expression of cell surface activation antigens (CD25 or HLA-DR), or interferon-gamma secretion, These results indicate that TNFR(80) is an important signal transducing receptor for the differentiation of NK cells induced by TNF and IL-2. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. IMMUNEX R&D CORP,SEATTLE,WA. UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. RI McVicar, Daniel/G-1970-2015 NR 41 TC 24 Z9 24 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 1995 VL 58 IS 2 BP 249 EP 255 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA RP559 UT WOS:A1995RP55900017 PM 7543923 ER PT J AU NOVOTNY, JA DUEKER, SR ZECH, LA CLIFFORD, AJ AF NOVOTNY, JA DUEKER, SR ZECH, LA CLIFFORD, AJ TI COMPARTMENTAL ANALYSIS OF THE DYNAMICS OF BETA-CAROTENE METABOLISM IN AN ADULT VOLUNTEER SO JOURNAL OF LIPID RESEARCH LA English DT Article DE BETA-CAROTENE; VITAMIN-A; METABOLISM; MATHEMATICAL MODELS; STABLE ISOTOPE; KINETICS; HUMAN ID VITAMIN-A; HUMAN PLASMA; ABSORPTION; CONVERSION; TISSUES; MODEL AB Metabolism of a 73 mu mol oral dose of beta-carotene-d(8) in olive oil was determined from plasma beta-carotene-d(8) and retinol-d(4) concentration-time curves in an adult male. beta-Carotene-d(8) and retinol-d(4) concentrations in serial plasma were measured using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS), respectively. Plasma beta-carotene-d(8) and retinol-d(4) concentration-time curves were described by a 5-term and a 3-term polyexponential equation, respectively, using an empirical description of beta-carotene metabolism. A physiologic compartmental model of beta-carotene metabolism was also constructed and tested. This model suggests that 22% of the beta-carotene dose is absorbed: 17.8% as intact beta-carotene and 4.2% as retinoid. Also, it suggests that both liver and enterocyte are important in converting beta-carotene to retinoid; 43% is converted in liver and 57% in enterocyte. Finally, it suggests that the mean residence time for beta-carotene is 51 days and that the 73 mu mole dose does not alter the fractional transfer coefficients of the system after absorption takes place. The issue of central versus eccentric cleavage of beta-carotene in humans can be studied with further modeling combined with use of appropriately labeled beta-carotene. C1 UNIV CALIF DAVIS,DEPT NUTR,DAVIS,CA 95616. USDA,BELTSVILLE HUMAN NUTR RES CTR,DIET & HUMAN PERFORMANCE LAB,BELTSVILLE,MD 20705. NCI,MATH BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [R01-DK-43098] NR 41 TC 84 Z9 88 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 1995 VL 36 IS 8 BP 1825 EP 1838 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR474 UT WOS:A1995RR47400018 PM 7595103 ER PT J AU SPIEGEL, S MILSTIEN, S AF SPIEGEL, S MILSTIEN, S TI SPHINGOLIPID METABOLITES - MEMBERS OF A NEW CLASS OF LIPID 2ND-MESSENGERS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE SPHINGOSINE; SPHINGOSINE-1-PHOSPHATE; SIGNAL TRANSDUCTION ID PROTEIN-KINASE-C; GROWTH-FACTOR RECEPTOR; HAMSTER OVARY CELLS; PHOSPHATIDIC-ACID PHOSPHOHYDROLASE; PHOSPHOLIPASE-D ACTIVATION; D-ERYTHRO-SPHINGOSINE; LEUKEMIC HL-60 CELLS; SWISS 3T3 CELLS; JURKAT T-CELLS; SIGNAL TRANSDUCTION C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. RP SPIEGEL, S (reprint author), GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007, USA. FU NIGMS NIH HHS [1RO1GM43880] NR 122 TC 220 Z9 223 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD AUG PY 1995 VL 146 IS 3 BP 225 EP 237 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA RQ270 UT WOS:A1995RQ27000001 PM 8568838 ER PT J AU BUSTAMANTE, JO HANOVER, JA LIEPINS, A AF BUSTAMANTE, JO HANOVER, JA LIEPINS, A TI THE ION-CHANNEL BEHAVIOR OF THE NUCLEAR-PORE COMPLEX SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE NUCLEAR PORE COMPLEX; NUCLEAR ION CHANNELS; GENE ACTIVITY; CONTROL OF GENE EXPRESSION; PATCH CLAMP; CARDIAC MYOCYTES; CELL NUCLEUS ID PERMEABILIZED MAMMALIAN-CELLS; PROTEIN IMPORT; CARDIAC MYOCYTES; ENVELOPE; IDENTIFICATION; ARCHITECTURE; MICROSCOPY; RETICULUM; SINGLE; HEART AB Macromolecule-conducting pores have been recently recognized as a distinct class of ion channels. The poor role of macromolecules as electrical charge carriers can be used to detect their movement along electrolyte-filled pores. Because of their negligible contribution to electrical ion currents, translocating macromolecules reduce the net conductivity of the medium inside the pore, thus decreasing the measured pore ion conductance. In the extreme case, a large translocating macromolecule can interrupt ion flow along the pore lumen, reflected as a negligible pore conductance. Therefore, ion conductance serves as a measurement of macromolecular transport, with lesser values indicating greater macromolecular translocation (in size and/or number). Such is the principle of operation of the widely used Coulter counter, an instrument for counting and sizing particles. It has long been known that macromolecules translocate across the central channel of nuclear pore complexes (NPCs), Recently, large conductance ion channel activity (100-1000 pS) was recorded from the nuclear envelope (NE) of various preparations and it was suggested that NPCs may be the source of this activity. Despite its significance to understanding the regulation of transcription, replication, mRNA export, and thus gene expression of normal and pathological states, no report has appeared demonstrating that this channel activity corresponds to ion flow along the central channel of the NPC, Here we present such a demonstration in adult mouse cardiac myocyte nuclei. In agreement with concepts introduced for macromolecule-conducting channels, our patch clamp experiments showed that ion conductance is reduced, and thus that ion flow is restricted during translocation of macromolecules containing nuclear targeting signals. Ion flow was blocked by mAb414, a monoclonal antibody raised against a major NPC glycoprotein and known to localize on the NPC channel where it blocks macromolecular transport. These results also establish patch clamp as a useful technique for the measurement of macromolecular translocation along the large central channel of the NPC and provide a basis for the design of future investigations of nuclear signaling for control of gene activity, mRNA export for gene expression, as well as other processes subservient to NPC-mediated nucleocytoplasmic exchange. C1 NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. MEM UNIV NEWFOUNDLAND,SCH MED,DIV BASIC MED SCI,ST JOHNS,NF A1B 3V6,CANADA. RP BUSTAMANTE, JO (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201, USA. NR 49 TC 63 Z9 63 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD AUG PY 1995 VL 146 IS 3 BP 239 EP 251 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA RQ270 UT WOS:A1995RQ27000002 PM 8568839 ER PT J AU BUSTAMANTE, JO OBERLEITHNER, H HANOVER, JA LIEPINS, A AF BUSTAMANTE, JO OBERLEITHNER, H HANOVER, JA LIEPINS, A TI PATCH-CLAMP DETECTION OF TRANSCRIPTION FACTOR TRANSLOCATION ALONG THE NUCLEAR-PORE COMPLEX CHANNEL SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE NUCLEAR PORE COMPLEX; NUCLEAR ION CHANNELS; GENE ACTIVITY; CONTROL OF GENE EXPRESSION; TRANSCRIPTION FACTORS; ONCOGENES; PROTOONCOGENES; AP-1; C-JUN; NF-KAPPA-B; SP1; PATCH CLAMP; CARDIAC MYOCYTES; CELL NUCLEUS ID NF-KAPPA-B; DNA-BINDING; CARDIAC MYOCYTES; JUN; FOS; ACTIVATION; PROTEIN; AP-1; PROMOTER; PROLIFERATION AB Transcription factors (TFs) are cytoplasmic proteins that play an essential role in gene expression. These proteins form multimers and this phenomenon is thought to be one of the mechanisms that regulate transcription. TF molecules reach their DNA binding sites through the large central channel of the nuclear pore complex (NPC). However, the NPC channel is known to restrict the translocation of molecules greater than or equal to 20-70 kD. Therefore, during their translocation, TF molecules and/or their multimers may plug the NPC channel and thus, interrupt ion flow through the channel, with a concomitant reduction in the ion conductance of the channel (gamma). Here we show with patch clamp that gamma is reduced during translocation of three major TFs: c-Jun (40 kD), NF-kappa B ( approximate to 50 kD), and SP1 ( approximate to 100 kD). Within a minute, femtomolar concentrations of these proteins reduced gamma suggesting a purely mechanical interaction between single TF molecules and the inner wall of the NPC channel. NPCs remained plugged for 0.5-3 hr in the absence of ATP but when ATP was added, channel plugging was shortened to < 5 min. After unplugging, channel closures were rarely observed and the number of functional channels increased. The transcription factors also stabilized the NPCs as shown by the extended duration of the preparations which allowed recordings for up to 72 hr. These observations are the first direct demonstration of the important role of NPCs in mediating nuclear translocation of TFs and, therefore, in forming part of the mechanisms regulating gene expression. The studies also demonstrate the potential of the patch clamp technique in quantifying TF translocation to the nucleus, mRNA export, and other processes governing gene expression. C1 UNIV WURZBURG,INST PHYSIOL,D-97070 WURZBURG,GERMANY. NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. MEM UNIV NEWFOUNDLAND,SCH MED,DIV BASIC MED SCI,ST JOHNS,NF A1B 3V6,CANADA. RP BUSTAMANTE, JO (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201, USA. NR 46 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD AUG PY 1995 VL 146 IS 3 BP 253 EP 261 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA RQ270 UT WOS:A1995RQ27000003 PM 8568840 ER PT J AU BUSTAMANTE, JO LIEPINS, A PRENDERGAST, RA HANOVER, JA OBERLEITHNER, H AF BUSTAMANTE, JO LIEPINS, A PRENDERGAST, RA HANOVER, JA OBERLEITHNER, H TI PATCH-CLAMP AND ATOMIC-FORCE MICROSCOPY DEMONSTRATE TATA-BINDING PROTEIN (TBP) INTERACTIONS WITH THE NUCLEAR-PORE COMPLEX SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE NUCLEAR PORE COMPLEX; NUCLEAR ION CHANNELS; GENE ACTIVITY; CONTROL OF GENE EXPRESSION; TATA-BINDING PROTEIN; TBP; PATCH CLAMP; ATOMIC FORCE MICROSCOPY; CELL NUCLEUS ID RNA POLYMERASE-II; CYTOPLASMIC PROTEINS; N-ACETYLGLUCOSAMINE; CARDIAC MYOCYTES; GAP-JUNCTIONS; GLYCOSYLATION; TRANSCRIPTION; CHANNELS; CELLS; GLYCOPROTEINS AB The universal TATA-binding protein, TBP, is an essential component of the multiprotein complex known as transcription factor IID (TFIID). This complex, which consists of TBP and TBP-associated factors (TAFs), is essential for RNA polymerase II-mediated transcription. The molecular size of human TBP (37.7 kD) is close to the passive diffusion limit along the transport channel of the nuclear pore complex (NPC), Therefore, the possibility exists that NPCs restrict TBP translocation to the nuclear interior. Here we show for the first time, with patch-clamp and atomic force microscopy (AFM), that NPCs regulate TBP movement into the nucleus and that TBP (10(-15)-10(-10) M) is capable of modifying NPC structure and function, The translocation of TBP was ATP-dependent and could be detected as a transient plugging of the NPC channels, with a concomitant transient reduction in single NPC channel conductance, gamma, to a negligible value. NPC unplugging was accompanied by permanent channel opening at concentrations greater than 250 pM. AFM images demonstrated that the TBP molecules attached to and accumulated on the NPC cytosolic side. NPC channel activity could be recorded for more than 48 hr. These observations suggest that three novel functions of TBP are: to stabilize NPC, to force the NPC channels into an open state, and to increase the number of functional channels. Since TBP is a major component of transcription, our observations are relevant to the understanding of the gene expression mechanisms underlying normal and pathological cell structure and function. C1 MEM UNIV NEWFOUNDLAND,SCH MED,DIV BASIC MED SCI,ST JOHNS,NF A1B 3V6,CANADA. JOHNS HOPKINS UNIV,WILMER EYE INST,BALTIMORE,MD 21287. NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. UNIV WURZBURG,INST PHYSIOL,D-97070 WURZBURG,GERMANY. RP BUSTAMANTE, JO (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201, USA. NR 63 TC 28 Z9 28 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD AUG PY 1995 VL 146 IS 3 BP 263 EP 272 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA RQ270 UT WOS:A1995RQ27000004 PM 8568841 ER PT J AU WEISS, GH GANDJBAKHCHE, AH MASOLIVER, J AF WEISS, GH GANDJBAKHCHE, AH MASOLIVER, J TI ISOTROPIZATION LENGTH FOR RANDOM-WALK MODELS OF PHOTON MIGRATION IN TURBID MEDIA SO JOURNAL OF MODERN OPTICS LA English DT Article ID ANISOTROPIC RANDOM-WALKS; OPTICAL-PROPERTIES; SCALING RELATIONSHIPS; DIFFUSION AB Analyses of photon transport in multiply scattering media are often formulated in terms of diffusion theory. Recently Gandjbakhche et al. have taken forward scattering into account by calculating the mean-squared displacement of an anisotropic random walk as a function of the step number and calculating a diffusion constant in terms of parameters that take anisotropy into account. This cannot yield accurate results at very short times when the motion is ballistic rather than diffusive. We translate the calculation of Gandjbakhche et ad. into continuous time. As expected, the short-time behaviour of the mean squared displacement is proportional to t(2) while at longer times it switches over to being proportional to t. The long-time limit of these results provides an isotropization length for the corresponding diffusion approximation. C1 UNIV BARCELONA,DEPT FIS FONAMENTAL,E-08028 BARCELONA,SPAIN. RP WEISS, GH (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 17 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0950-0340 J9 J MOD OPTIC JI J. Mod. Opt. PD AUG PY 1995 VL 42 IS 8 BP 1567 EP 1574 DI 10.1080/09500349514551371 PG 8 WC Optics SC Optics GA RN929 UT WOS:A1995RN92900002 ER PT J AU SCHOEN, TJ MAZURUK, K WALDBILLIG, RJ POTTS, J BEEBE, DC CHADER, GJ RODRIGUEZ, IR AF SCHOEN, TJ MAZURUK, K WALDBILLIG, RJ POTTS, J BEEBE, DC CHADER, GJ RODRIGUEZ, IR TI CLONING AND CHARACTERIZATION OF A CHICK-EMBRYO CDNA AND GENE FOR IGF-BINDING PROTEIN-2 SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-I; MESSENGER-RNAS; DEVELOPMENTAL REGULATION; SEQUENCE-ANALYSIS; INSULIN; EXPRESSION; RAT; PROMOTER; TRANSCRIPTION; IDENTIFICATION AB We have isolated and characterized a cDNA for IGF-binding protein-2 (IGFBP-2) and its gene from the chick embryo. Using primers from a conserved region of the mammalian IGFBP-2 sequence, a cDNA clone (1.6 kb) was isolated from an embryonic day-18 chick retina cDNA library. Although the clone was truncated at the 5' end,the complete coding sequence was obtained from 5' rapid amplification of cDNA ends and genomic sequencing. The open reading frame encoded a 311 amino acid precursor protein which contains a putative 36 residue signal peptide. The mature 275 amino acid protein had a predicted M(r) of 33 500 and exhibited 71, 68, 68 and 66% identity to rat, bovine, ovine and human IGFBP-2 cDNA respectively, with conservation of all 18 cysteines. The cDNA contained an RGD peptide but lacked a putative ATP-binding motif. A single transcript of approximately 2.3 kb was present in embryonic day-15 eye, brain, skeletal muscle, heart and intestine, but was virtually absent from embryonic day-15 liver. The chicken IGFBP-2 gene spanned approximately 38 kb, consisted of four exons, and was similarly organized to that of the rat and human. Southern blot analysis of chicken genomic DNA suggested that it is encoded by a single gene. The sequence information from the avian IGFBP-2 should be of value in examining the role of IGFBP-2 in vertebrate development. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. RP SCHOEN, TJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 304,9000 ROCKVILLE PIKE,BETHESDA,MD 20905, USA. NR 45 TC 42 Z9 44 U1 0 U2 2 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD AUG PY 1995 VL 15 IS 1 BP 49 EP 59 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RM975 UT WOS:A1995RM97500005 PM 8546813 ER PT J AU PHILLIPS, CL YAMAKAWA, K ADELSTEIN, RS AF PHILLIPS, CL YAMAKAWA, K ADELSTEIN, RS TI CLONING OF THE CDNA-ENCODING HUMAN NONMUSCLE MYOSIN HEAVY CHAIN-B AND ANALYSIS OF HUMAN TISSUES WITH ISOFORM-SPECIFIC ANTIBODIES SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; CELLULAR MYOSIN; DIFFERENTIAL EXPRESSION; VASCULAR DEVELOPMENT; COMPLETE SEQUENCE; MESSENGER-RNAS; NERVOUS-SYSTEM; DNA-SEQUENCE; CELLS; KINASE AB Previously, we reported the sequence of cDNA clones encoding amino acids 63 through 723 of the human nonmuscle myosin heavy chain-B isoform. In this paper, we present the derived sequence of the remaining 1303 amino adds along with 5' and 3' untranslated sequences. We made use of the differences between the derived nonmuscle myosin heavy chain-A and -B amino add sequences to raise isoform-specific antibodies. Immunoblot analysis reveals a differential expression of both myosin heavy chain isoforms in a variety of human adult and foetal tissues and cells. When extracts of human adult aorta were subjected to gel electrophoresis, two distinct Coomassie Blue-stained bands and a fused band were seen migrating at approximately 200 kDa. These bands can be detected with four different specific antibodies recognizing the two different smooth muscle myosin heavy chain isoforms (204 kDa and 200 kDa) and the two different nonmuscle myosin heavy chain isoforms (A and B). Using immunohistochemistry, we confirmed the presence of the four different isoforms in adult and foetal aortas. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. YAMAGUCHI UNIV,SCH MED,DEPT INTERNAL MED 2,UBE,YAMAGUCHI 755,JAPAN. OI Phillips, Carrie/0000-0002-0256-0736; Adelstein, Robert/0000-0002-8683-2144 NR 35 TC 100 Z9 101 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD AUG PY 1995 VL 16 IS 4 BP 379 EP 389 DI 10.1007/BF00114503 PG 11 WC Cell Biology SC Cell Biology GA RP923 UT WOS:A1995RP92300003 PM 7499478 ER PT J AU RALL, JE AF RALL, JE TI INSTRUMENTAL BIOLOGY OR THE DISUNITY OF SCIENCE - ROSENBERG,A SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP RALL, JE (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 1995 VL 183 IS 8 BP 557 EP 558 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RR324 UT WOS:A1995RR32400017 ER PT J AU SAKAI, N KAUFMAN, S MILSTIEN, S AF SAKAI, N KAUFMAN, S MILSTIEN, S TI PARALLEL INDUCTION OF NITRIC-OXIDE AND TETRAHYDROBIOPTERIN SYNTHESIS BY CYTOKINES IN RAT GLIAL-CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CYTOKINES; NITRIC OXIDE; TETRAHYDROBIOPTERIN; MICROGLIA; ASTROCYTES; MACROPHAGES ID MICROGLIAL CELLS; L-ARGININE; ALVEOLAR MACROPHAGES; NEUROLOGICAL DISEASE; ENDOTHELIAL-CELLS; SYNTHASE ACTIVITY; INTERFERON-GAMMA; BLOOD MONOCYTES; BRAIN; INTERLEUKIN-2 AB Activation of monocyte-derived macrophages with cytokines leads to the induction of nitric oxide synthase. Much less is known about the effects of cytokines on microglia, resident brain macrophages, or on astrocytes. In this study, we compared the induction by lipopolysaccharide, interferon-gamma, and tumor necrosis factor-alpha of nitric oxide production and synthesis of tetrahydrobiopterin, the required cofactor for nitric oxide synthase, in microglia and peritoneal macrophages. Activation of microglia induced parallel increases in nitric oxide and intracellular tetrahydrobiopterin levels, although induction of the latter appears to be somewhat more sensitive to diverse stimulators. As with macrophages, inducible nitric oxide production in microglia was blocked by inhibitors of tetrahydrobiopterin biosynthesis. Interleukin-2, an important component of the neuroimmunomodulatory system, was only a weak activator of microglia by itself but potently synergized with interferon-gamma to stimulate production of both nitric oxide and tetrahydrobiopterin, Astrocytes were also activated by lipopolysaccharide and combinations of cytokines but showed a somewhat different pattern of responses than microglia. Biopterin synthesis was increased to higher levels in astrocytes than in microglia, but maximal induction of nitric oxide production required higher concentrations of cytokines than microglia and the response was much lower. These results suggest that tetrahydrobiopterin synthesis in glial cells is a potential target for therapeutic intervention in acute CNS infections whose pathology may be mediated by overproduction of nitric oxide. C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NR 54 TC 50 Z9 50 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 AUG PY 1995 VL 65 IS 2 BP 895 EP 902 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RJ657 UT WOS:A1995RJ65700055 PM 7616251 ER PT J AU SUNDAR, KS KAMARAJU, LS DINGFELDER, J MCMAHON, J GOLLAPUDI, S WILSON, WH KONG, LY HONG, JS WEISS, JM LEE, JE AF SUNDAR, KS KAMARAJU, LS DINGFELDER, J MCMAHON, J GOLLAPUDI, S WILSON, WH KONG, LY HONG, JS WEISS, JM LEE, JE TI BETA-ENDORPHIN ENHANCES THE REPLICATION OF NEUROTROPIC HUMAN-IMMUNODEFICIENCY-VIRUS IN FETAL PERIVASCULAR MICROGLIA SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE AIDS; CYTOKINES; MICROGLIA; OPIATE; HIV REPLICATION ID AIDS DEMENTIA COMPLEX; HIV-INFECTED PATIENTS; CEREBROSPINAL-FLUID; ZIDOVUDINE AZT; RAT-BRAIN; HTLV-III; EXPRESSION; CELLS; MACROPHAGES; MECHANISMS AB The effect of an endogenous opiate, beta-endorphin, on the replication of HIV was investigated in brain perivascular microglia. Beta-endorphin enhanced the synthesis of p-24 antigen and transactivation of HIV promoter. Dialysed culture supernatants of endorphin-treated microglia re-activated latent HIV infection. These culture supernatants showed elevated levels of interleukin-1 beta, IL-6 and tumor necrosis factor alpha. Sub-optimal concentration of beta-endorphin potentiated GP-120-induced synthesis of these cytokines. Nalaxone reversed beta-endorphin-induced, but not GP-120-induced, cytokine production and enhanced HIV replication. These results suggest that endogenous opiates may contribute to the progression of AIDS dementia complex. C1 E TOWNE OBGYN,CHAPEL HILL,NC. EVE SURG CTR,LOS ANGELES,CA. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. NIEHS,MOLEC NEUROSCI LAB,RES TRIANGLE PK,NC 27709. EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30322. RP SUNDAR, KS (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT,NEUROIMMUNOL LAB,BOX 3552,DURHAM,NC 27710, USA. FU NIMH NIH HHS [MH51524] NR 47 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD AUG PY 1995 VL 61 IS 1 BP 97 EP 104 DI 10.1016/0165-5728(95)00089-K PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA RW064 UT WOS:A1995RW06400013 PM 7560019 ER PT J AU ROBINSON, DL BOWMAN, EM KERTZMAN, C AF ROBINSON, DL BOWMAN, EM KERTZMAN, C TI COVERT ORIENTING OF ATTENTION IN MACAQUES .2. CONTRIBUTIONS OF PARIETAL CORTEX SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LIGHT-SENSITIVE NEURONS; LATERAL INTRAPARIETAL AREA; INFERIOR TEMPORAL NEURONS; SACCADE-RELATED ACTIVITY; RHESUS-MONKEY; FUNCTIONAL-PROPERTIES; VISUAL RESPONSES; CORTICOCORTICAL CONNECTIONS; ASSOCIATION CORTEX; EYE-MOVEMENTS AB 1. To understand some of the contributions of parietal cortex to the dynamics of visual spatial attention, we recorded from cortical cells of monkeys performing attentional tasks. We studied 484 neurons in the intraparietal sulcus and adjacent gyral tissue of two monkeys. We measured phasic responses to peripheral Visual stimuli while the monkeys attended toward or away from the stimuli or when attention was not controlled. Neurons were tested while the monkeys gazed at a spot of light (simple fixation task), actively attended to a foveal target (foveal attention task), performed a reaction time task. (cued reaction time task), made saccadic eye movements to visual targets (saccade task), or responded to a repetitious peripheral target (probability task). 2. In a previous paper we demonstrated that monkeys, Like humans, responded more quickly to visual targets when the targets followed briefly flashed visual cues (validly cued targets) (Bowman ct al. 1993). It has been hypothesized that the cue attracts attention to its locus and results in faster reaction times (Posner 1980). In the present physiological studies, visual cues consistently excited these neurons when they were hashed in the receptive held. Such activity might signal a shift of attention. Visual targets that fell within the receptive field and that immediately followed the cue evoked relatively weak responses. This response was due to a relative refractory period. 3. Next we tested attentional processes in these tasks that were independent of the visual response to the cue. We placed the cue outside of the receptive field and the target within the receptive field. We found that 23% of these cells had a significant decrease in their firing rate to validly cued targets in their receptive fields under these conditions. Strong responses were evoked by the same target when the cue was flashed in the opposite hemifield (invalidly cued targets). Thus this group of neurons responded best when attention was directed toward the opposite hemifield. 4. For another group of parietal cells (13%) there was an enhanced response to targets in the visual receptive field when the cue was in the same hemifield. For the remaining 64% of the cells there was no significant modulation in this task. 5. The cued reaction time task involved exogenous control of attention; the sensory cue gave spatial and temporal direction to attention. We used several other tasks to test for endogenous control of attention. For some cells, when a monkey simply gazed at a spot of light there was only a modest response to peripheral visual stimuli; when the monkey performed the foveal attention task there was an increase in the intensity of response of the same cell to the same peripheral stimulus. Thus, when attention was directed away from the Visual receptive held by endogenous control, there was a similar augmentation of response. 6. When an animal responded repetitiously to targets outside of the visual receptive field (probability task), there was a strong response evoked when the stimulus appeared unexpectedly within the receptive field. Weak responses were elicited at expected locations. The modulations in the cued reaction time, foveal attention, and probability tasks were quantitatively similar. These observations are also consistent with other data showing that a group of parietal cells responded best when attention was not directed into the visual receptive field. This was true whether attention was manipulated exogenously or endogenously. 7. Approximately 45% of the neurons tested discharged in relation to saccadic eye movements, and the largest number of such cells was located in the posterior bank of the intraparietal sulcus. 8. We conclude from these experiments that parietal cells participate in attentional processes. All respond to the visual cue that directs attention, and this may signal a shift of attention. When the visual cue was positioned near the receptive held, differential activity was produced, all of which may signal attentional shifts. Certain of these cells also had modulations in endogenous tasks that augmented the response when attention was away from the receptive held; such activity could signal a shift of attention to the receptive field. These data provide some mechanisms for contributions of parietal cortex to the dynamics of visual attention. RP ROBINSON, DL (reprint author), NEI,SENSORIMOTOR RES LAB,VISUAL BEHAV SECT,BLDG 49,RM 2A50,BETHESDA,MD 20892, USA. RI Bowman, Eric/A-3780-2010 NR 65 TC 140 Z9 141 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1995 VL 74 IS 2 BP 698 EP 712 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA RN658 UT WOS:A1995RN65800019 PM 7472375 ER PT J AU ROBINSON, DL KERTZMAN, C AF ROBINSON, DL KERTZMAN, C TI COVERT ORIENTING OF ATTENTION IN MACAQUES .3. CONTRIBUTIONS OF THE SUPERIOR COLLICULUS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VISUAL SPATIAL ATTENTION; PARIETAL ASSOCIATION CORTEX; BEHAVING MONKEY; EYE-MOVEMENTS; RESPONSES; LESIONS; CELLS; MECHANISMS; PULVINAR; MODULATION AB 1. The present experiments were conducted to study physiological mechanisms in the superior colliculus and their relation to visual spatial attention. We used a cued reaction time task studied in detail previously (Bowman et al. 1993; Posner 1980). Monkeys learned to fixate a spot of Light and release a bar when a target light appeared. Cues on the same side as the target(valid cue) were associated with faster reaction times than those on the opposite side (invalid cue). The difference in reaction times is hypothesized to be a measure of attention. 2. A total of 79 neurons within the superficial layers of the superior colliculi of two monkeys were studied. When the cues and targets were positioned so that both were within the visual receptive field, the cues excited the cells, and this produced a refractoriness to the targets for the following 400 ms. Both the ON and OFF responses to the cue were constant under all conditions. 3. These neurons were also tested with the cue just outside of the visual receptive field. This was done to avoid refractory effects from the cue; there was no significant modulation of the response to the target under these conditions. The visual responses of neurons in the intermediate layers of the superior colliculus also responded equivalently under these conditions. 4. When the activity of cells within the foveal representation was compared during the performance of three tasks, there differential activity. The appearance of the fixation point during the performance of the cued reaction time task led to a strong, transient discharge. There was an equivalent response when the monkey performed a foveal attention task; there was little or no; activation to the fixation point during a simple fixation task where no additional behavioral response was required. There was no change in activity of these cells at later times when the cue shifted the direction of attention. 5. Regions of the colliculus were modified with injections of muscimol, a gamma-aminobutyric acid agonist. The injection produced a slowing of reaction times to all targets in the affected representation. The reaction times to targets in the ipsilateral visual field were not changed. Comparable injections of saline had no effect 6. These data show that the visual cells within the superior colliculus were activated in the performance of attentional task that were independent of eye movements. The responses of cells to the onset of the cue could signal exogenously initiated shifts of attention. However, these cells appear to exhibit no endogenous attentional modulations. In contrast, cells in the foveal representation have attentional modulations and may signal engagement of attention at the fovea. RP ROBINSON, DL (reprint author), NEI,SENSORIMOTOR RES LAB,VISUAL BEHAV SECT,BLDG 49,RM 2A50,BETHESDA,MD 20892, USA. NR 37 TC 100 Z9 100 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1995 VL 74 IS 2 BP 713 EP 721 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA RN658 UT WOS:A1995RN65800020 PM 7472376 ER PT J AU FISCHER, C HATZIDIMITRIOU, G WLOS, J KATZ, J RICAURTE, G AF FISCHER, C HATZIDIMITRIOU, G WLOS, J KATZ, J RICAURTE, G TI REORGANIZATION OF ASCENDING 5-HT AXON PROJECTIONS IN ANIMALS PREVIOUSLY EXPOSED TO THE RECREATIONAL DRUG (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA, ECSTASY) SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 5-HT; NEUROTOXICITY; AMPHETAMINES; SPROUTING; REGENERATION; REINNERVATION ID CENTRAL NORADRENALINE NEURONS; CENTRAL SEROTONERGIC NEURONS; NEONATAL 6-HYDROXYDOPAMINE TREATMENT; RAT INFERIOR OLIVE; NONHUMAN-PRIMATES; UPTAKE SITES; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHYLENEDIOXYMETHYLAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; RHESUS-MONKEYS AB The recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, ''ecstasy'') is a methamphetamine derivative that selectively destroys central 5-HT axons and axon terminals in animals and, possibly, humans. The fate of 5-HT neurons following MDMA injury is uncertain. In particular, while it is known that central 5-HT axons can undergo regenerative sprouting after MDMA injury, it has not been determined whether they reestablish the original innervation pattern. To address this question, the present studies examined 5-HT innervation patterns in animals lesioned with MDMA 12-18 months previously. Both rodents (rats) and nonhuman primates (squirrel monkeys) were examined, since there is indication that serotonergic recovery after MDMA injury may be species dependent. 5-HT axon projections were studied neurochemically, autoradiographically and immunocytochemically. In both rodents and nonhuman primates previously lesioned with MDMA, substantial serotonergic axonal sprouting was observed. However, in a few rats and in most squirrel monkeys, the reinnervation pattern was highly abnormal: distant targets (e.g., dorsal neocortex) remained denervated, while some proximal targets (e.g., amygdala, hypothalamus) were reinnervated or hyperinnervated. Although the specific determinants of axonal recovery after MDMA injury remain to be identified, it appears that axons which initially sustain more severe damage, are longer, or are more highly arborized have low probability of recovering. The observation that some brain regions remain denervated, while others are reinnervated or hyperinnervated suggests that, under some circumstances, MDMA injury can lead to a lasting reorganization of ascending 5-HT axon projections. Such lasting changes in brain innervation, documented here in MDMA-treated animals, may have implications for humans using MDMA recreationally. C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA05707, DA06275] NR 74 TC 173 Z9 174 U1 2 U2 7 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 AUG PY 1995 VL 15 IS 8 BP 5476 EP 5485 PG 10 WC Neurosciences SC Neurosciences & Neurology GA RP560 UT WOS:A1995RP56000005 PM 7643196 ER PT J AU NI, BH WU, X YAN, GM WANG, J PAUL, SN AF NI, BH WU, X YAN, GM WANG, J PAUL, SN TI REGIONAL EXPRESSION AND CELLULAR-LOCALIZATION OF THE NA+-DEPENDENT INORGANIC-PHOSPHATE COTRANSPORTER OF RAT-BRAIN SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BRAIN NA+-DEPENDENT INORGANIC PHOSPHATE COTRANSPORTER; REGIONAL AND DEVELOPMENTAL EXPRESSION; PHOSPHATE TRANSPORT AND CELLULAR METABOLISM; NMDA RECEPTOR ID IMPAIRED ENERGY-METABOLISM; DEPLETION; HYPERALIMENTATION; PHOSPHORYLATION; MECHANISMS; RECEPTOR; PROTEIN AB We have recently isolated and identified a brain specific Na+-dependent inorganic phosphate (P-i) cotransporter cDNA (rBNPI) from a rat brain cDNA library (Ni et al., 1994). We now report the regional and developmental expression, as well as the cellular localization, of rBNPI mRNA in the rat brain. In situ hybridization histochemistry reveals that rBNPI mRNA is selectively expressed in neuron-enriched regions of the adult rat brain, such as the cerebral cortex, hippocampus, and cerebellum. Cellular localization of rBNPI transcripts reveals expression in both pyramidal and granule neurons in these regions. By contrast, little to no hybridization signal was observed in white matter-enriched areas such as the corpus callosum. The expression of rBNPI mRNA was determined during pre- and postnatal development of the rat CNS. From embryonic day 17 to early postnatal day 10 (PND 10), there is a rather widespread but diffuse pattern of rBNPI expression in brain. During late postnatal development, however, the expression of rBNPI mRNA becomes confined to discrete populations of neurons in the cerebral cortex, hippocampus, and cerebellum. Thus, rBNPI expression is developmentally regulated and abundant levels of mRNA are found in rather discrete populations of neurons in the adult rat brain. The latter suggests that rBNPI may serve to selectively regulate intracellular P-i transport in certain neurons for either metabolic and (or) signaling events. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202. RP NI, BH (reprint author), ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285, USA. NR 26 TC 113 Z9 121 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 AUG PY 1995 VL 15 IS 8 BP 5789 EP 5799 PG 11 WC Neurosciences SC Neurosciences & Neurology GA RP560 UT WOS:A1995RP56000030 PM 7643219 ER PT J AU WOOD, KA YOULE, RJ AF WOOD, KA YOULE, RJ TI THE ROLE OF FREE-RADICALS AND P53 IN NEURON APOPTOSIS IN-VIVO SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CEREBELLUM; X-IRRADIATION; METHYLAZOXYMETHANOL; APOPTOSIS; P53; FREE RADICALS ID PRIMITIVE NEUROECTODERMAL TUMORS; DEVELOPING MOUSE CEREBELLUM; INDUCED CELL-DEATH; RAT CEREBELLUM; X-IRRADIATION; GENE; MEDULLOBLASTOMA; RADIATION; PROTEIN; CORTEX AB Apoptosis is a mechanism of cell death operative in the normal development and regulation of vertebrate tissues and organ cellularity. During the postnatal development of the mouse cerebellum, extensive granule neuron apoptosis occurs that may regulate the final granule cell to Purkinje cell stoichiometry observed in the adult. Cerebellar granule cells are highly sensitive to genotoxic agents such as gamma-irradiation and methylazoxymethanol during the first 2 weeks of postnatal development. We demonstrate that ionizing radiation induces extensive cerebellar granule cell death via apoptosis in vivo. In p53 null mice, however, the cerebellar granule cells do not undergo apoptosis in response to gamma-irradiation. In mice heterozygous for the p53 allele, the granule cells apoptosis is delayed, indicating an intermediate response. The developmental apoptosis of cerebellar granule cells, however, occurs similarly in wild-type and p53 null mice. Therefore, neurons undergo p53-dependent and p53-independent apoptosis, depending upon the initiating stimulus that triggers DNA fragmentation. In contrast to x-ray damage, the extensive death of cerebellar granule cells induced by methylazoxymethanol was found to be independent of the DNA fragmentation characteristic of apoptosis, and was also independent of expression of p53. Ablation of neuron progenitor cells with genotoxic agents may occur by p53-dependent apoptosis or by p53-independent mechanisms not associated with DNA fragmentation. RP WOOD, KA (reprint author), NIH,SURG NEUROL BRANCH,BIOCHEM SECT,BLDG 10,ROOM 5D37,10 CTR DR,BETHESDA,MD 20892, USA. NR 41 TC 198 Z9 204 U1 0 U2 1 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 AUG PY 1995 VL 15 IS 8 BP 5851 EP 5857 PG 7 WC Neurosciences SC Neurosciences & Neurology GA RP560 UT WOS:A1995RP56000036 PM 7643225 ER PT J AU RAM, Z SHAWKER, TH BRADFORD, MH DOPPMAN, JL OLDFIELD, EH AF RAM, Z SHAWKER, TH BRADFORD, MH DOPPMAN, JL OLDFIELD, EH TI INTRAOPERATIVE ULTRASOUND-DIRECTED RESECTION OF PITUITARY-TUMORS SO JOURNAL OF NEUROSURGERY LA English DT Article DE PITUITARY TUMOR; TRANSSPHENOIDAL SURGERY; ULTRASOUND; MAGNETIC RESONANCE IMAGING ID CUSHING DISEASE; MR; MICROADENOMAS; ADENOMAS; HORMONE AB Microadenomas of the pituitary vary in size, particularly those related to Cushing's disease. They are often not visualized on preoperative magnetic resonance (MR) imaging and may be difficult to find during surgical exploration of the pituitary. To enhance intraoperative localization of pituitary adenomas, we assessed the feasibility of using ultrasound to detect and localize pituitary tumors. Intraoperative ultrasound (IS) in the axial and sagittal planes was performed with an Intrascan system using a 12-MHz mechanically oscillating, end-firing transducer. Interpretation of the scans was performed by two individuals, who were usually blinded to the results of preoperative MR imaging or petrosal sinus sampling. Twenty-eight patients were examined. Eighteen of these patients had microadenomas (1.5-7 mm), all with Cushing's disease; nine had macroadenomas (10-20 mm), three of which were adrenocorticotropic hormone-secreting, three growth hormone-secreting, two thyroid-stimulating hormone-secreting, and one nonfunctioning; and one patient had an intrasellar craniopharyngioma. Normal sellar and parasellar structures, such as intrapituitary cysts, the intracavernous carotid arteries, and the diaphragma sella were easily visualized. Twenty-three of the 28 tumors, including 13 of the 18 microadenomas, were detected on IS (82% sensitivity). Tumors were seen as hyperechoic masses in 19 patients, mixed echogenicity in three, and isoechoic in one. In most macroadenomas IS allowed visualization of the interface between the tumor and the normal pituitary gland. These results indicate the potential of IS to aid the intraoperative localization and definition of pituitary tumors. C1 NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NR 10 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1995 VL 83 IS 2 BP 225 EP 230 DI 10.3171/jns.1995.83.2.0225 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RL110 UT WOS:A1995RL11000007 PM 7616266 ER PT J AU KARAMERIS, AM WORTHY, E GORGOULIS, VG QUEZADO, M ANASTASSIADES, OT AF KARAMERIS, AM WORTHY, E GORGOULIS, VG QUEZADO, M ANASTASSIADES, OT TI P53 GENE ALTERATIONS IN SPECIAL TYPES OF BREAST-CARCINOMA - A MOLECULAR AND IMMUNOHISTOCHEMICAL STUDY IN ARCHIVAL MATERIAL SO JOURNAL OF PATHOLOGY LA English DT Article DE P53; C-ERBB-2; SPECIAL TYPES OF BREAST CARCINOMA; ALLELIC DELETION; GENE MUTATION; PCR HYDROLINK METHOD ID COLORECTAL CARCINOMAS; EMBRYO FIBROBLASTS; ALLELE LOSSES; MUTANT P53; CANCER; MUTATIONS; EXPRESSION; AMPLIFICATION; PROTEIN; CHROMOSOME-17 AB The p53 locus on the short arm of chromosome 17 at 17p13.1 was examined for small genomic deletions and mutations in 23 formalin-fixed, paraffin-embedded cases of special types of breast carcinoma (six medullary, seven apocrine, five differentiated tubular, and five papillary). p53 mutations in the evolutionarily conserved exons 5-9 were detected in 11 cases (four apocrine, two papillary, two medullary, and three differentiated tubular), using the novel non-radioactive PCR-based Hydrolink mutation detection enhancement (MDE) method, and confirmed by direct sequencing of the PCR products. Missense mutations causing amino acid substitutions were evenly distributed among exons. One case of apocrine carcinoma showed a polymorphism at codon 213 (CGA-->CGG). Twelve out of 23 cases were found to express a strong nuclear signal against CM-1 and DO-7, two anti-p53-specific antibodies. Small genomic deletions in the vicinity of the p53 locus were detected in 11 tumours (three papillary, three differentiated tubular, two medullary, and three apocrine carcinomas), using the multiplex PCR method. No statistical correlation was found between deletions at 17p13.1 and p53 mutations (P<0 . 5). In addition, p53 mutations and immunoexpression correlated with the c-erbB-2 gene product, an oncogenic protein that has been implicated in cell cycle control (P<0 . 001). Our findings suggest that genomic alterations of the p53 gene are quite common events associated with special types of breast carcinoma, particularly of the apocrine subtype, but the prognostic value is unlikely to be of clinical importance. C1 ARMY GEN HOSP 401,DEPT PATHOL,ATHENS,GREECE. DICKINSON COLL HUB,PHILADELPHIA,PA. RED CROSS HOSP,DEPT PATHOL,ATHENS,GREECE. NIH,BETHESDA,MD 20892. GEN HOSP,DEPT PATHOL,ATHENS,GREECE. NR 40 TC 20 Z9 20 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD AUG PY 1995 VL 176 IS 4 BP 361 EP 372 DI 10.1002/path.1711760407 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA RR798 UT WOS:A1995RR79800006 PM 7562251 ER PT J AU MUELLER, BU PIZZO, PA AF MUELLER, BU PIZZO, PA TI CANCER IN CHILDREN WITH PRIMARY OR SECONDARY IMMUNODEFICIENCIES - REPLY SO JOURNAL OF PEDIATRICS LA English DT Letter RP MUELLER, BU (reprint author), NCI, PEDIAT BRANCH, BLDG 10, BETHESDA, MD 20892 USA. NR 4 TC 0 Z9 0 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 AUG PY 1995 VL 127 IS 2 BP 335 EP 335 DI 10.1016/S0022-3476(95)70335-7 PG 1 WC Pediatrics SC Pediatrics GA RN497 UT WOS:A1995RN49700043 ER PT J AU COSTA, PT MCCRAE, RR AF COSTA, PT MCCRAE, RR TI PRIMARY TRAITS OF EYSENCK P-E-N SYSTEM - 3-FACTOR AND 5-FACTOR SOLUTIONS SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article ID NEO PERSONALITY-INVENTORY; 5 FACTOR MODEL; 5-FACTOR MODEL; BIG 5; SCALES; DIMENSIONS AB The Eysenck Personality Profiler (EPP) a set of 21 scales measuring primary traits hypothesized to be definers of Neuroticism, Extraversion, and Psychoticism factors, was administered to 229 adults together with the Eysenck Personality Questionnaire-Revised (H. J. Eysenck & S. B. G. Eysenck, 1991) and the Revised NEO Personality Inventory (NEO-PI-R; P. T. Costa & R. R. McCrae, 1992b). Correlations of EPP scales with NEO-PI-R facet scales provided preliminary evidence supporting the convergent and discriminant validity of the EPP scales. However, varimax and targeted validimax factor analyses suggested that some EPP scales were misclassified and that EPP scales could better be understood in terms of the 5-factor model than the intended 3-factor model. RP COSTA, PT (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 47 TC 146 Z9 146 U1 3 U2 29 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD AUG PY 1995 VL 69 IS 2 BP 308 EP 317 DI 10.1037//0022-3514.69.2.308 PG 10 WC Psychology, Social SC Psychology GA RM328 UT WOS:A1995RM32800009 PM 7643307 ER PT J AU XIAO, WH BENNETT, GJ AF XIAO, WH BENNETT, GJ TI SYNTHETIC OMEGA-CONOPEPTIDES APPLIED TO THE SITE OF NERVE INJURY SUPPRESS NEUROPATHIC PAINS IN RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INTRAVENOUS LIDOCAINE INFUSION; DORSAL-ROOT GANGLION; PERIPHERAL NEUROPATHY; SPONTANEOUS DISCHARGE; DIABETIC NEUROPATHY; SENSATION LIKE; NEURALGIA; MONONEUROPATHY; SENSITIZATION; GUANETHIDINE AB In patients and animals with painful peripheral neuropathies, spontaneous ectopic discharge from injured primary afferents is hypothesized to maintain a central state of hyperexcitability that underlies hyperalgesia and allodynia. Temporary suppression of this discharge allows the central state to normalize, such that hyperalgesia and allodynia are absent or reduced until the resumption of the discharge rekindles central hyperexcitability. Previous work suggests that Ca++ channels are involved in the genesis of spontaneous discharge from injured afferents. We applied SNX-111 and SNX-124 (0.13.0 mu g), synthetic homologs of omega-conopeptides (MVIIA and GVIA, respectively) and potent blockers of neuronal N-type voltage-sensitive Ca++ channels, to the site of nerve injury via chronically implanted perineural cannulae in rats with an experimental painful peripheral neuropathy (the chronic constriction injury model). heat-hyperalgesia and mechano-allodynia were reduced for at least 3 hr. Drug application to a normal nerve had no effect on responses to heat or mechanical stimuli. These results suggest that N-type Ca++ channel blockers may be useful in the treatment of the abnormal pains that occur after nerve injury. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 58 TC 95 Z9 101 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1995 VL 274 IS 2 BP 666 EP 672 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RN983 UT WOS:A1995RN98300012 PM 7636726 ER PT J AU BRONSTEIN, DM HONG, JS AF BRONSTEIN, DM HONG, JS TI EFFECTS OF SULPIRIDE AND SCH-23390 ON METHAMPHETAMINE-INDUCED CHANGES IN BODY-TEMPERATURE AND LETHALITY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TYROSINE-HYDROXYLASE ACTIVITY; DOPAMINE RELEASE; RECEPTOR ANTAGONIST; AMPHETAMINE; COCAINE; RATS; SCH-23390; D-1; ANTIDEPRESSANTS; NEUROLEPTICS AB Data from human and animal studies suggest that hyperpyrexia contributes to both the neurotoxic and the lethal effects of stimulant drugs such as methamphetamine (METH). Because many of the effects of METH involve the release of dopamine from CNS neurons, we examined the effects of D-1 and D-2 dopamine receptor antagonists on METH-induced lethality and determined whether these effects correlated with changes in body temperature. In the first set of experiments, we found that the D-2 antagonist sulpiride (SUL; 20, 40 or 80 mg/kg) potentiated the lethality caused by a single injection of METH (10 mg/kg). Pretreatment with the D-1 antagonist SCH 23390 (SCH; 0.5 mg/kg) reduced the lethality induced by METH alone or by SUL/METH. Other D-2 or 5-hydroxytryptamine antagonists prevented, rather than potentiated, METH-induced lethality. In a second set of experiments, rectal temperatures were recorded in METH-injected animals pretreated with SCH or SUL. METH caused a significant increase (i.e., above vehicle-injected levels) in body temperature at 2.5 hr after injection. The effects of SCH or SUL pretreatment on METH-induced changes in body temperature suggest that the lethality-potentiating and -protective effects of SUL and SCH, respectively, were not due to altered thermoregulatory responses. These data support the idea that D-1 receptor activation is an important event in the lethality caused by METH and that SUL may potentiate D-1 receptor activation by augmenting METH-induced DA release. C1 NATL INST ENVIRONM HLTH SCI,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NR 55 TC 20 Z9 20 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 AUG PY 1995 VL 274 IS 2 BP 943 EP 950 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RN983 UT WOS:A1995RN98300049 PM 7636758 ER PT J AU YAN, GM IRWIN, RP LIN, SZ WELLER, M WOOD, KA PAUL, SM AF YAN, GM IRWIN, RP LIN, SZ WELLER, M WOOD, KA PAUL, SM TI DIPHENYLHYDANTOIN INDUCES APOPTOTIC CELL-DEATH OF CULTURED RAT CEREBELLAR GRANULE NEURONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D-ASPARTATE RECEPTOR; GROWTH-FACTOR; PHENYTOIN THERAPY; PROTEIN-SYNTHESIS; NEUROTOXICITY; MECHANISMS; RNA; DEGENERATION; TEMPERATURE; INHIBITION AB Apoptosis is one form of physiological or programmed cell death responsible for the selective elimination of various cell types during development. We have observed and characterized a delayed-type of neurotoxicity induced in cultured cerebellar granule neurons by diphenylhydantoin. Diphenylhydantoin toxicity of cerebellar granule neurons is time and concentration dependent. Morphological studies using Nomarski optics and staining with the fluorescent dye Hoechst 33258 demonstrate that diphenylhydantoin-induced neurotoxicity of cerebellar granule neurons is associated with cytoplasmic blebbing, heterochromatic clumping and condensation of chromatin that precede cell death. Unlike glutamate toxicity (excitotoxicity) diphenylhydantoin-induced neurotoxicity of cerebellar granule neurons is attenuated by actinomycin D and cycloheximide, and is associated with nucleosomal size DNA fragmentation. Since we have previously reported that depolarization of cultured cerebellar granule neurons with high concentrations of K+ promotes the survival of these neurons by blocking apoptosis, we examined the effects of diphenylhydantoin on the K+-evoked increase in intracellular calcium. Using microfluorimetry and fura-2 to measure intracellular calcium we found that neurotoxic concentrations of diphenylhydantoin markedly reduce the increase in intracellular calcium associated with elevated extracellur potassium. Taken together, these data demonstrate that exposure of cultured cerebellar granule neurons to pharmacologically relevant concentrations of diphenylhydantoin results in a delayed type of neurotoxicity characterized by the biochemical and morphological features of apoptosis. C1 LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN. FU FIC NIH HHS [F05-TWO-4591-02] NR 45 TC 34 Z9 59 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1995 VL 274 IS 2 BP 983 EP 990 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RN983 UT WOS:A1995RN98300054 PM 7636763 ER PT J AU URQUHART, SG HITCHCOCK, AP LEAPMAN, RD PRIESTER, RD RIGHTOR, EG AF URQUHART, SG HITCHCOCK, AP LEAPMAN, RD PRIESTER, RD RIGHTOR, EG TI ANALYSIS OF POLYURETHANES USING CORE EXCITATION SPECTROSCOPY .1. MODEL POLYURETHANE FOAM POLYMERS SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Article DE POLYURETHANES; PHASE SEGREGATION; ANALYSIS BY CORE EXCITATION SPECTROSCOPY ID ENERGY-LOSS-SPECTROSCOPY; BLOCK COPOLYMERS; ELECTRON; SPECTROMETER; MORPHOLOGY; XANES AB The C1s, N1s, and O1s excitation spectra of model methylenediphenyldiisocyanate (MDI) polyurethanes with well known structures have been recorded using electron energy loss spectroscopy (EELS) in an electron microscope. These spectra are compared to the core excitation spectra of selected small molecule analogue species (recorded by gas phase EELS) in order to identify transitions characteristic of various structural components found in polyurethanes. A more detailed report on the small molecule analogue spectra is presented in the following article. Spectral features characteristic of the different structural components in polyurethanes are identified in the spectra of the model polymers. These can be used as the basis for chemical studies of micron or submicron sized segregated phases in flexible polyurethane polymers. (C) 1995 John Wiley & Sons, Inc. C1 MCMASTER UNIV,INST MAT RES,HAMILTON,ON L8S 4M1,CANADA. NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. DOW CHEM CO USA,FREEPORT,TX 77541. RI Urquhart, Stephen/A-6237-2014 OI Urquhart, Stephen/0000-0002-6415-6341 NR 37 TC 23 Z9 23 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-6266 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD AUG PY 1995 VL 33 IS 11 BP 1593 EP 1602 DI 10.1002/polb.1995.090331104 PG 10 WC Polymer Science SC Polymer Science GA RJ381 UT WOS:A1995RJ38100004 ER PT J AU ALLEN, AJ LEONARD, H SWEDO, SE AF ALLEN, AJ LEONARD, H SWEDO, SE TI CURRENT KNOWLEDGE OF MEDICATIONS FOR THE TREATMENT OF CHILDHOOD ANXIETY DISORDERS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DRUG THERAPY; ANXIETY DISORDERS; AFFECTIVE DISORDERS; CHILDREN; ADOLESCENTS ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; DOUBLE-BLIND; PANIC DISORDER; SCHOOL PHOBIA; SOCIAL PHOBIA; CLOMIPRAMINE TREATMENT; AUTISTIC DISORDER; CONTROLLED TRIAL; ELECTIVE MUTISM AB Objective: This report will review the costs, risks, and benefits of potentially useful medications for the treatment of children and adolescents with anxiety disorders and will identify areas where data are limited and additional research is needed. Method: A Medline-assisted review of the literature was performed. Attention was given to dosage, response, and side effects of medications. Wherever possible, blinded, controlled medication trials in children with anxiety disorders (diagnosed by structured criteria) were targeted for use as the primary references. Relatively few systematic studies were found, so information from open trials and case reports also was included, as were controlled trials in adult populations. Results: The largest body of work supporting the use of medications for childhood anxiety came from studies of obsessive-compulsive disorder, where clomipramine and fluoxetine have been found effective in systematic studies. in other childhood anxiety disorders, there are conflicting data about the efficacy of medications, such as tricyclic antidepressants, benzodiazepines, serotonin reuptake inhibitors, beta-blockers, and monoamine oxidase inhibitors. Conclusions: This review of the systematic pharmacological trials for childhood anxiety disorders revealed only 13 controlled studies: 5 for obsessive-compulsive disorder, 4 for school refusal/separation anxiety disorder, and 4 for avoidant/overanxious disorder or mixed diagnostic groups. Medications appear to be helpful for childhood anxiety disorders, although definitive pharmacotherapeutic data are lacking for many conditions. A systematic study of these medications is required to establish safety and efficacy in the pediatric age group. Evolving diagnostic criteria and terminology, the presence of comorbid diagnoses (especially affective disorders), and inadequate medication dosages may be factors hindering research in this field. Until additional research is done, clinicians must carefully consider the relative risk-to-benefit ratio when prescribing these medications. C1 NIMH,UNIT CHILDHOOD ANXIETY DISORDERS,BETHESDA,MD 20892. RP ALLEN, AJ (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT SECT,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 84 TC 45 Z9 47 U1 1 U2 4 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 AUG PY 1995 VL 34 IS 8 BP 976 EP 986 DI 10.1097/00004583-199508000-00007 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RL320 UT WOS:A1995RL32000007 PM 7665455 ER PT J AU RICHTERS, JE ARNOLD, LE JENSEN, PS ABIKOFF, H CONNERS, CK GREENHILL, LL HECHTMAN, L HINSHAW, SP PELHAM, WE SWANSON, JM AF RICHTERS, JE ARNOLD, LE JENSEN, PS ABIKOFF, H CONNERS, CK GREENHILL, LL HECHTMAN, L HINSHAW, SP PELHAM, WE SWANSON, JM TI NIMH COLLABORATIVE MULTISITE MULTIMODAL TREATMENT STUDY OF CHILDREN WITH ADHD .1. BACKGROUND AND RATIONALE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE ATTENTION-DEFICIT HYPERACTIVITY DISORDER; CHILDHOOD DISORDERS; MULTIMODAL TREATMENT; PSYCHOPHARMACOLOGICAL TREATMENT; PSYCHOSOCIAL TREATMENT ID ATTENTION-DEFICIT DISORDER; MINIMAL BRAIN-DYSFUNCTION; DSM-III DISORDERS; HYPERACTIVE-CHILDREN; FOLLOW-UP; SELF-CONTROL; HYPERKINETIC-CHILDREN; STIMULANT MEDICATION; CONDUCT DISORDER; PREADOLESCENT CHILDREN AB Objective: The National Institute of Mental Health's recently initiated 5-year, multisite, multimodal treatment study of children with attention-deficit hyperactivity disorder (MTA) is the first major clinical trial in its history focused on a childhood mental disorder. This article reviews the major scientific and clinical bases for initiating the MTA. Method: A selective review of the literature is presented in the service of describing the estimated prevalence of ADHD among children and adolescents, its core clinical features, evidence concerning psychopharmacological and psychosocial treatment effects, and related research issues and trends leading to the development of the MTA. Results: Despite decades of treatment research and clinical practice, there is an insufficient basis for answering the following manifold question: under what circumstances and with what child characteristics (comorbid conditions, gender, family history home environment, age, nutritional/metabolic status, etc.) do which treatments or combinations of treatment (stimulants, behavior therapy parent training, school-based intervention) have what impacts (improvement, stasis, deterioration) on what domains of child functioning (cognitive, academic, behavioral, neurophysiological, neuropsychological, peer relations, family relations), for how long (short versus long term), to what extent (effect sizes, normal versus pathological range), and why (processes underlying change)? Conclusions: The important scientific, clinical, and public health issues nested within this manifold question provide both the impetus and scaffolding for the MTA. C1 LONG ISL JEWISH MED CTR,NEW HYDE PK,NY 11042. DUKE UNIV,DURHAM,NC 27706. COLUMBIA UNIV,NEW YORK,NY 10027. MCGILL UNIV,MONTREAL,PQ,CANADA. UNIV CALIF BERKELEY,BERKELEY,CA. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV CALIF IRVINE,IRVINE,CA 92717. RP RICHTERS, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROOM 18C-17,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650; Richters, John/0000-0002-6780-1828 FU NIMH NIH HHS [MH50467, U01-MH50453, U01-MH50461] NR 153 TC 175 Z9 179 U1 5 U2 18 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 AUG PY 1995 VL 34 IS 8 BP 987 EP 1000 DI 10.1097/00004583-199508000-00008 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RL320 UT WOS:A1995RL32000008 PM 7665456 ER PT J AU SHIRANI, J ZAFARI, AM ROBERTS, WC AF SHIRANI, J ZAFARI, AM ROBERTS, WC TI MORPHOLOGIC FEATURES OF FOSSA OVALIS MEMBRANE ANEURYSM IN THE ADULT AND ITS CLINICAL-SIGNIFICANCE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ATRIAL SEPTAL ANEURYSM; MITRAL-VALVE PROLAPSE; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; PREVALENCE; EVENTS AB Objectives. This study evaluated morphologic features of fossa ovalis membrane aneurysm and associated cardiac abnormalities that may predispose to systemic embolism. Background. An increasing number of fossa ovalis membrane aneurysms are diagnosed by echocardiography. Higher frequencies of such aneurysms have been reported in patients with embolic stroke. Methods. The hearts of 20 adults with fossa ovalis membrane aneurysms (mean [+/-SD] age 62 +/- 19 years, rang 24 to 87; 12 women [60%], 8 men [40%]) were examined. The areas of excised atrial septum, fossa ovalis membrane and fossa ovalis were measured. An aneurysm was defined as the ratio of the fossa ovalis membrane to fossa ovalis area greater than or equal to 1.5. Results. Compared with a control group of 20 adults (mean age 58 +/- 21 years, range 18 to 86; 12 women [60%], 8 men [40%]), the 20 patients with fossa ovalis membrane aneurysm had larger (711 +/- 240 vs. 203 +/- 105 mm(2), p < 0.0001) and thinner fossa ovalis membranes (0.6 +/- 0.1 vs. 1.9 +/- 0.9 mm(2), p < 0.0001). The mean ratio of the fossa ovalis membrane to fossa ovalis area,vas 2.1 +/- 0.4 in patients,vith and 1.2 +/- 0.1 in those without fossa ovalis membrane aneurysm. Patent foramen ovale,vas seen in 14 (70%) of 20 patients with fossa ovalis membrane aneurysm and in 4 (20%) of 20 control subjects (p = 0.0005). Conclusions. Fossa ovalis membrane aneurysm is characterized by thinning and marked redundancy without adherent thrombi or fibrin tags. Mitral valve prolapse, dilated atria, intracardiac thrombi and patent foramen ovale are frequently seen in association with fossa ovalis membrane aneurysm and may explain the increased frequency of embolic stroke in patients with such aneurysms. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 19 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1995 VL 26 IS 2 BP 466 EP 471 DI 10.1016/0735-1097(95)80024-B PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM094 UT WOS:A1995RM09400025 PM 7608452 ER PT J AU SHIOTA, T JONES, M TEIEN, DE YAMADA, I PASSAFINI, A GE, SP SAHN, DJ AF SHIOTA, T JONES, M TEIEN, DE YAMADA, I PASSAFINI, A GE, SP SAHN, DJ TI DYNAMIC CHANGE IN MITRAL REGURGITANT ORIFICE AREA - COMPARISON OF COLOR DOPPLER-ECHOCARDIOGRAPHIC AND ELECTROMAGNETIC FLOWMETER-BASED METHODS IN A CHRONIC ANIMAL-MODEL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FLOW CONVERGENCE REGION; VALVULAR REGURGITATION; VALVE AREA; BLOOD-FLOW; QUANTIFICATION; INVITRO; VOLUME; VALIDATION; MOMENTUM; GEOMETRY AB Objectives. The aim of the present study was to investigate dynamic changes in the mitral regurgitant orifice using electromagnetic flow probes and flowmeters and the color Doppler how convergence method. Background. Methods for determining mitral regurgitant orifice areas have been described using flow convergence imaging with a hemispheric isovelocity surface assumption. However, the shape of how convergence isovelocity surfaces depends on many factors that change during regurgitation. Methods. In seven sheep with surgically created mitral regurgitation, 18 hemodynamic states were studied. The aliasing distances of flow convergence were measured at 10 sequential points using two ranges of aliasing velocities (0.20 to 0.32 and 0.56 to 0.72 m/s), and instantaneous flow rates were calculated using the hemispheric assumption. Instantaneous regurgitant areas were determined from the regurgitant how rates obtained from both electromagnetic flowmeters and flow convergence divided by the corresponding continuous wave velocities. Results. The regurgitant orifice sizes obtained using the electromagnetic how method usually increased to maximal size in early to midsystole and then decreased in late systole. Patterns of dynamic changes in orifice area obtained by flow convergence were not the same as those delineated by the electromagnetic flow method. Time-averaged regurgitant orifice areas obtained by flow convergence using lower aliasing velocities overestimated the areas obtained by the electromagnetic pow method ([mean +/- SD] 0.27 +/- 0,14 vs. 0.12 +/- 0.06 cm(2), p < 0.001), whereas flow convergence, using higher aliasing velocities, estimated the reference areas more reliably (0.15 +/- 0.06 cm(2)). Conclusions. The electromagnetic how method studies uniformly demonstrated dynamic change in mitral regurgitant orifice area and suggested limitations of the Row convergence method. C1 NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,CLIN CARE CTR CNGENITAL HEART DIS,PORTLAND,OR. FU NHLBI NIH HHS [HL 43287] NR 39 TC 33 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1995 VL 26 IS 2 BP 528 EP 536 DI 10.1016/0735-1097(95)80033-D PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RM094 UT WOS:A1995RM09400034 PM 7608460 ER PT J AU MARESPERLMAN, JA SUBAR, AF BLOCK, G GREGER, JL LUBY, MH AF MARESPERLMAN, JA SUBAR, AF BLOCK, G GREGER, JL LUBY, MH TI ZINC INTAKE AND SOURCES IN THE US ADULT-POPULATION - 1976-1980 SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE ZINC; NUTRITION SURVEYS; HUMAN; NUTRIENT INTAKE ID NHANES-II SURVEY; QUANTITATIVE DATA; NUTRIENT SOURCES; AMERICAN DIET; FOODS; MINERALS; ABSORPTION; WOMEN AB Objective: To determine levels of intake and food sources of zinc in 1976-80 in US adults between the ages of 19 and 74. Methods: Dietary data from 24-hour recalls collected in the Second National Health and Nutrition Examination Survey were analyzed. Levels of zinc intake were compared between demographic subgroups using analysis of variance. The contribution of individual foods to overall zinc consumed was also estimated, Results: Mean daily intakes (+/-SEM) were 15.5 mg +/- 0.4 and 9.8 mg +/- 0.2 in white men and women, respectively. Mean daily intake estimates in black men and women (12.3 mg +/- 0.8 and 7.8 mg +/- 0.3, respectively) were significantly lower. Lower intakes were observed in women versus men, in older (65 to 74 years) versus younger (19 to 34 years) age groups, and among people with lower versus higher education and income levels. Lower zinc intakes in women and older persons could be mainly attributed to lower overall energy intake compared with gender and age counterparts. However, lower intakes in blacks and persons with lower education or income levels were not explained by differences in energy intake and may be attributed to differences in food selections. Meat and milk products contributed the majority of zinc in recalled diets, accounting for 56 and 60% of total zinc intake in blacks and whites, respectively. Conclusions: Levels and sources of zinc intake in 1976-80 were higher than in more recent national surveys, suggesting that zinc intakes may be declining. Population groups more likely to have lower intakes were women, older adults, blacks, and those with lower levels of education and higher poverty levels. C1 NCI,BETHESDA,MD 20892. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53706. RP MARESPERLMAN, JA (reprint author), UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,610 N WALNUT ST-405 WARF,MADISON,WI 53705, USA. RI Block, Gladys/E-3304-2010 FU NEI NIH HHS [EY08012] NR 38 TC 37 Z9 39 U1 1 U2 3 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD AUG PY 1995 VL 14 IS 4 BP 349 EP 357 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RN051 UT WOS:A1995RN05100007 PM 8568111 ER PT J AU KANT, AK BALLARDBARBASH, R SCHATZKIN, A AF KANT, AK BALLARDBARBASH, R SCHATZKIN, A TI EVENING EATING AND ITS RELATION TO SELF-REPORTED BODY-WEIGHT AND NUTRIENT INTAKE IN WOMEN, CSFII 1985-86 SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE MEAL PATTERNS; MEAL DISTRIBUTION; DIET QUALITY; BODY WEIGHT; OBESITY; MEAL FREQUENCY; CSFII; NFCS; NUTRITION SURVEY; NUTRIENT INTAKE ID FOOD; MEN AB Objective: We investigated the association of extent of daily energy intake from evening food intake with self-reported body weight and nutrient intake. Design: Using data from the 1985-86 CSFII, we estimated the proportion of daily energy from foods/beverages reportedly consumed after 5 p.m. on 4 non-consecutive days by 1802 women, aged 19-50 years. Results: The mean +/- SE of 4-day average energy from evening food intake was 46 +/- 0.4%. Body mass index was not associated with percent energy from evening food intake in unadjusted or multiple-covariate-adjusted regression analyses. In multiple-covariate-adjusted regression models, percent energy from fat, protein, and grams of alcohol reported were positively associated with percent energy from evening food intake (p < 0.05); while percent energy from carbohydrate, and percent RDA of vitamins C, B-6, and folate were inversely associated with evening eating. Conclusions: The results do not support the hypothesis regarding the association of relative weight with percent energy from evening food intake. However, statistically significant differences in intake of some nutrients in relation to extent of evening food intake were noted. C1 NCI,BETHESDA,MD 20892. RP KANT, AK (reprint author), CUNY QUEENS COLL,FLUSHING,NY 11367, USA. NR 15 TC 19 Z9 19 U1 0 U2 0 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD AUG PY 1995 VL 14 IS 4 BP 358 EP 363 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RN051 UT WOS:A1995RN05100008 PM 8568112 ER PT J AU SLESINSKI, MJ SUBAR, AF KAHLE, LL AF SLESINSKI, MJ SUBAR, AF KAHLE, LL TI TRENDS IN USE OF VITAMIN AND MINERAL SUPPLEMENTS IN THE UNITED-STATES - THE 1987 AND 1982 NATIONAL-HEALTH INTERVIEW SURVEYS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Note C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP SLESINSKI, MJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PL N,SUITE 313,BETHESDA,MD 20892, USA. NR 11 TC 108 Z9 109 U1 0 U2 3 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 1995 VL 95 IS 8 BP 921 EP 923 DI 10.1016/S0002-8223(95)00255-3 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RM863 UT WOS:A1995RM86300019 PM 7636088 ER PT J AU ROBBINS, J WAHL, P SAVAGE, P ENRIGHT, P POWE, N LYLES, M AF ROBBINS, J WAHL, P SAVAGE, P ENRIGHT, P POWE, N LYLES, M TI HEMATOLOGICAL AND BIOCHEMICAL LABORATORY VALUES IN OLDER CARDIOVASCULAR HEALTH STUDY PARTICIPANTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article AB OBJECTIVE: To define reference hematologic and biochemical lab values in older individuals. DESIGN: Randomly selected, age- and gender-stratified participants. SETTING: Visits by participants to four research clinics. PATIENTS: A total of 5201 participants in the Cardiovascular Health Study, an observational study of older Medicare-eligible individuals living at home. MEASUREMENT: Information about health status, previous illness, and medication use was obtained from participants and/or their MDs. This information was used to define a healthy subset of the population. Blood samples were obtained for Cholesterol, HDL and LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen, factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood count, hematocrit, hemoglobin, and platelet count. RESULTS: Significant differences were found for age group and/or gender for all mean values. Many tests were significantly different from the generally accepted reference ranges used in clinical laboratories. CONCLUSIONS: In some situations accepted laboratory norms for the general population can not be extrapolated to older adults. There are implications for both research and clinical practice. C1 UNIV WASHINGTON,DEPT PUBL HLTH,SEATTLE,WA 98195. NHLBI,BETHESDA,MD 20892. UNIV ARIZONA,CTR RESP SCI,TUCSON,AZ. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD. BOWMAN GRAY SCH MED,DEPT GERIATR MED,WINSTON SALEM,NC. RP ROBBINS, J (reprint author), UNIV CALIF DAVIS,DEPT MED,DIV GEN MED,2221 STOCKTON BLVD,SACRAMENTO,CA 95817, USA. NR 16 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1995 VL 43 IS 8 BP 855 EP 859 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RM829 UT WOS:A1995RM82900002 PM 7636091 ER PT J AU BROWN, SL SALIVE, ME PAHOR, M FOLEY, DJ CORTI, MC LANGLOIS, JA WALLACE, RB HARRIS, TB AF BROWN, SL SALIVE, ME PAHOR, M FOLEY, DJ CORTI, MC LANGLOIS, JA WALLACE, RB HARRIS, TB TI OCCULT CAFFEINE AS A SOURCE OF SLEEP PROBLEMS IN AN OLDER POPULATION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID INSOMNIA; ASPIRIN; SYSTEM; HEALTH AB OBJECTIVE: To evaluate the impact of caffeine in medication on sleep complaints in a community population of persons aged 67 or older. DESIGN: Cross-sectional analysis. SETTING: Iowa 65+ Rural Health Study. PARTICIPANTS: Those who completed their own interview, including a section on the use of medications, during the third annual in-person follow-up in 1984-1985. MEASUREMENTS: Main outcomes: trouble falling asleep or other sleep complaints. Covariates: use of caffeine-containing medication, spasmolytic, or sympathomimetic drug; number of drugs used; depressive symptoms; self-perceived perceived health; comorbidity, hip fracture, arthritis, ulcer of stomach or intestines; and consumption of caffeinated beverages. RESULTS: The prevalence of caffeinated medication use by participants was 5.4%. Those reporting the use of any caffeine-containing medication were at an increased risk of having trouble falling asleep (Odds Ratio [OR] = 1.79, 95% confidence interval [CI] = 1.19-2.68). There was no significant risk of other reported nighttime or daytime sleep problems associated with use of caffeine-containing drugs. Even after adjusting for other factors that could interfere with initiation of sleep, such as painful disease, depressive symptoms, polypharmacy, use of specific medications known to interfere with sleep, and coffee consumption, the use of caffeine-containing medication still presented a significantly increased risk of having trouble falling asleep (OR = 1.60, CI 1.04-2.46). Although those participants using over-the-counter analgesic medication containing caffeine had an increased risk of trouble falling asleep (OR = 1.88, CI = 1.22-2.90), there was no significant risk of trouble falling asleep for those who took similar noncaffeinated OTC analgesic drugs (OR = 1.26, CI = 0.87-1.83). CONCLUSIONS: The use of caffeine-containing medication is associated with sleep problems. Healthcare providers should be aware of potential problems associated with over-the-counter medications containing caffeine and should counsel patients about the potential of sleep problems. Older patients should be encouraged to read the label on medications and to select drugs that are caffeine-free when that is possible. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV CATTOLICA SACRO CUORE,CATTEDRA GERONTOL,ROME,ITALY. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA. NR 19 TC 12 Z9 12 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1995 VL 43 IS 8 BP 860 EP 864 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RM829 UT WOS:A1995RM82900003 PM 7636092 ER PT J AU LENFANT, C TAYLOR, O RUFFIN, J EPPS, C AF LENFANT, C TAYLOR, O RUFFIN, J EPPS, C TI PROCEEDINGS OF THE FORUM ON THE STATUS OF CORONARY HEART-DISEASE IN BLACKS - A BLUEPRINT FOR FORGING LINKAGES TO IMPROVE MEDICAL-MANAGEMENT AND TO ENHANCE PUBLIC-HEALTH ACTION - PREFACE SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD AUG PY 1995 VL 87 IS 8 SU S BP 589 EP 589 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RP683 UT WOS:A1995RP68300001 ER PT J AU LENFANT, C STOKES, L EPPS, C TAYLOR, OL RUFFIN, J MALVEAUX, F AF LENFANT, C STOKES, L EPPS, C TAYLOR, OL RUFFIN, J MALVEAUX, F TI FORUM ON THE STATUS OF CORONARY HEART-DISEASE IN BLACKS - OPENING REMARKS SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD AUG PY 1995 VL 87 IS 8 SU S BP 592 EP 595 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA RP683 UT WOS:A1995RP68300002 ER PT J AU LENFANT, C AF LENFANT, C TI SETTING THE AGENDA FOR RESEARCH AND EDUCATION ON CORONARY HEART-DISEASE SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD AUG PY 1995 VL 87 IS 8 SU S BP 596 EP 596 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RP683 UT WOS:A1995RP68300003 ER PT J AU LENFANT, C AF LENFANT, C TI CHD AND AFRICAN-AMERICANS OUTREACH STRATEGY - FOCUS ON HYPERTENSION SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD AUG PY 1995 VL 87 IS 8 SU S BP 604 EP 604 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RP683 UT WOS:A1995RP68300005 ER PT J AU RUFFIN, J AF RUFFIN, J TI FORGING ALLIANCES TO MEET FUTURE-RESEARCH AND RESEARCH TRAINING NEEDS SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article RP RUFFIN, J (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD AUG PY 1995 VL 87 IS 8 SU S BP 624 EP 626 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RP683 UT WOS:A1995RP68300013 PM 7674358 ER PT J AU HEIDENBERG, HB SESTERHENN, IA GADDIPATI, JP WEGHORST, CM BUZARD, GS MOUL, JW SRIVASTAVA, S AF HEIDENBERG, HB SESTERHENN, IA GADDIPATI, JP WEGHORST, CM BUZARD, GS MOUL, JW SRIVASTAVA, S TI ALTERATION OF THE TUMOR-SUPPRESSOR GENE P53 IN A HIGH FRACTION OF HORMONE-REFRACTORY PROSTATE-CANCER SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATIC NEOPLASMS; GENES, P53; PROTEIN P53; GENES, SUPPRESSOR, TUMOR ID LI-FRAUMENI SYNDROME; PRONE FAMILY; CARCINOMA; MUTATIONS; EXPRESSION; MUTANT; ACCUMULATION; PROGRESSION; GROWTH; CELLS AB Purpose: We studied the role of p53 tumor suppressor gene alteration in prostate cancer progression by demonstrating a difference in abnormal p53 findings between early and hormone refractory disease. Materials and Methods: The study included p53 immunohistochemistry of 26 archival transurethral resection specimens from patients with radiation recurrent and hormone refractory disease, 27 untreated primary tumors and 8 untreated metastatic lesions. p53 mutation analysis of tumor deoxyribonucleic acid (DNA) from microdissected specimens was done by cold single strand conformational polymorphism and DNA sequencing. Results: Elevated p53 protein was present in 16 of 17 hormone refractory specimens (94%), 4 of 8 untreated metastatic tumors (50%) and 6 of 27 primary untreated tumors (22%). DNA analysis of representative specimens with elevated p53 confirmed p53 gene alterations in 9 of 11 cases (82%). Conclusions: Our study revealed a clear progression of increased p53 alteration from untreated primary to hormone refractory disease (p<0.00005). C1 UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,BETHESDA,MD 20814. ARMED FORCES INST PATHOL,WALTER REED ARMY MED CTR,DEPT SURG,UROL SERV,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,WALTER REED ARMY MED CTR,DEPT CLIN INVEST,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT GENITOURINARY PATHOL,WASHINGTON,DC 20306. UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,CTR PROSTRATE DIS RES,FREDERICK,MD. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BCDP,FREDERICK,MD 21702. NR 36 TC 138 Z9 138 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 AUG PY 1995 VL 154 IS 2 BP 414 EP 421 DI 10.1016/S0022-5347(01)67065-4 PN 1 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA RJ050 UT WOS:A1995RJ05000023 PM 7609105 ER EF