FN Thomson Reuters Web of Science™ VR 1.0 PT J AU ANDERSON, LM LOGSDON, D RUSKIE, S FOX, SD ISSAQ, HJ KOVATCH, RM RIGGS, CM AF ANDERSON, LM LOGSDON, D RUSKIE, S FOX, SD ISSAQ, HJ KOVATCH, RM RIGGS, CM TI PROMOTION BY POLYCHLORINATED-BIPHENYLS OF LUNG AND LIVER-TUMORS IN MICE SO CARCINOGENESIS LA English DT Article ID N-NITROSODIMETHYLAMINE; MOUSE LUNG; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ADIPOSE-TISSUE; BREAST-CANCER; BLOOD; PCBS; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; AROCLOR-1254; CONGENERS AB Polychlorinated biphenyls (PCB), which are tumor promoters, have been found in human tissues for decades. Their contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion. Epidemiological associations have been seen between PCB exposure or tissue content and cancer at several sites. In rodents, tumor promotion by PCBs has been little studied in tissues other than liver. Previously, in an experiment modeling infant carcinogen exposure following PCBs received in milk, lung and liver tumors, initiated neonatally in mice by the environmental nitrosamine N-nitrosodimethylamine (NDMA), were promoted by later treatment with Aroclor 1254. The present study was undertaken to confirm and characterize the effects of Aroclor 1254 on tumor number, latency, size and malignancy. Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 (250 mg/kg) on day 8, and killed at intervals. Eight PCB congeners were quantified in the carcasses. Incidences of mice with NDMA-initiated lung tumors at 28 weeks of age were increased 2.5-fold by PCBs. Multiplicities of lung tumors were enhanced four-fold by PCBs at 28 and 52 weeks. By 72 weeks tumor numbers were similar in the NDMA-only and NDMA-PCB groups. Liver tumors first occurred in significant numbers at 52 weeks and only in mice receiving both NDMA and PCBs. As for the lung, at 72 weeks the incidence was high in both the NDMA-only and NDMA -PCB groups. Sizes of tumors and liver carcinoma incidence were not altered by PCB treatment. Carcass analysis revealed a significant positive association between lung tumor numbers at 28 weeks and relative percentage of 2,2',4,4',5-pentachlorobiphenyl, with no other correlations. The results confirm that PCBs promote lung as well as liver tumors, by triggering the early appearance of latent initiated tumors otherwise presenting in old age. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PATHOL ASSOCIATES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. RP ANDERSON, LM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FT DETRICK,FREDERICK,MD 21702, USA. NR 21 TC 22 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1994 VL 15 IS 10 BP 2245 EP 2248 DI 10.1093/carcin/15.10.2245 PG 4 WC Oncology SC Oncology GA PM733 UT WOS:A1994PM73300028 PM 7955061 ER PT J AU ANNA, CH MARONPOT, RR PEREIRA, MA FOLEY, JF MALARKEY, DE ANDERSON, MW AF ANNA, CH MARONPOT, RR PEREIRA, MA FOLEY, JF MALARKEY, DE ANDERSON, MW TI RAS PROTOONCOGENE ACTIVATION IN DICHLOROACETIC ACID-INDUCED, TRICHLOROETHYLENE-INDUCED AND TETRACHLOROETHYLENE-INDUCED LIVER-TUMORS IN B6C3F1 MICE SO CARCINOGENESIS LA English DT Article ID MOUSE-LIVER; LUNG-TUMORS; MACROMOLECULAR INTERACTIONS; PROTOONCOGENE ACTIVATION; SPECIES-DIFFERENCES; H-RAS; PHARMACOKINETICS; CARCINOGENICITY; RATS; TRICHLOROACETATE AB The frequency and mutation spectra of proto-oncogene activation in hepatocellular neoplasms induced by tetrachloroethylene, trichloroethylene and dichloroacetic acid were examined to help define the molecular basis for their carcinogenicity. H-ras codon 61 activation was not significantly different among dichloroacetic acid-and trichloroethylene-induced and combined historical and concurrent control hepatocellular tumors (62%, 51% and 69% respectively). The mutation spectra of H-ras codon 61 mutations showed a significant decrease in AAA and increase in CTA mutations for dichloroacetic acid-and trichloroethylene-induced tumors when compared to combined controls. The H-ras codon 61 mutation frequency for tetrachloroethylene-induced tumors was significantly lower (24%) than that of combined controls and also that of the two other chemicals. Mutations at codons 13 and 117 plus a second exon insert contributed 4% to the total H-vas frequencies for trichloroethylene and tetrachloroethylene. There was also a higher incidence of K-ras activation (13%) in tetrachloroethylene-induced tumors than in the other chemically induced or control tumors. Four liver tumors were found to contain insertions of additional bases within the second exon of K- or H-ras. These findings suggest that exposure to dichloroacetic acid, trichloroethylene and tetrachloroethylene provides a selective growth advantage to spontaneously occurring mutations in codon 61 of H-ras and, at the same time, is responsible for a small number of unique molecular lesions suggestive of either a random genotoxic mode of action or a non-specific result of secondary DNA damage. However, the absence of ras activation in many of the liver neoplasms suggests that alternative mechanisms are also important in B6C3F1 mouse hepatocarcinogenesis. C1 ENVIRONMENT HLTH RES & TESTING INC, LEXINGTON, KY 40503 USA. RP ANNA, CH (reprint author), NIEHS, ENVIRONM CARCINOGENESIS PROGRAM, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 47 TC 59 Z9 62 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1994 VL 15 IS 10 BP 2255 EP 2261 DI 10.1093/carcin/15.10.2255 PG 7 WC Oncology SC Oncology GA PM733 UT WOS:A1994PM73300030 PM 7955063 ER PT J AU CHEN, LC SLY, L DE LUCA, LM AF CHEN, LC SLY, L DE LUCA, LM TI HIGH DIETARY RETINOIC ACID PREVENTS MALIGNANT CONVERSION OF SKIN PAPILLOMAS INDUCED BY A 2-STAGE CARCINOGENESIS PROTOCOL IN FEMALE SENCAR MICE SO CARCINOGENESIS LA English DT Note ID TUMORS; TUMORIGENESIS; ISOTRETINOIN; INHIBITION; CARCINOMA; CANCER; BETA AB We have previously reported that high dietary retinoic acid (RA; 30 mu g/g diet) inhibits carcinoma formation in a two-stage skin carcinogenesis protocol, using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as the tumor-promoter in female SENCAR mice. We next asked whether switching the diets from high to control levels of RA and vice versa would influence carcinoma formation. Mice at 3 weeks of age were initiated with DMBA (20 mu g) once, followed by 20 weekly applications of TPA (2 mu g). At 3 weeks of age mice were weaned onto a diet containing either 3 (control) or 30 (high) mu g RA/g diet. Half of the mice from either dietary group were switched to the other diet at 20 weeks of age, when papilloma formation was at its peak. These four groups are designated RA 3 mu g, RA 30 mu g, RA 3/30 mu g and RA 30/3 mu g groups. As previously found, papilloma formation (including incidence and yield) was not significantly affected by dietary treatment. However, high dietary RA inhibited carcinoma formation; specifically cumulative carcinoma incidence (18.5-23.1% versus 50%) and yield (0.19-0.23 versus 0.68) were significantly lower (P < 0.05) in the high dietary RA treatment groups than the RA 3 mu g control group, as was the carcinoma conversion efficiency (2.1-3.8% versus 9.4%). The beneficial effect on carcinoma formation was still evident when excess RA was given late during the carcinogenesis process (i.e, the RA 3/30 mu g group). Moreover, a residual effect of excess RA was also seen after the dietary RA was switched to the control level at 20 weeks of age, when papilloma yield was highest (i.e. the RA 30/3 mu g group). It is therefore concluded that the chemopreventive effect of high dietary RA on skin carcinogenesis induced by a two-stage carcinogenesis protocol with DMBA and TPA resides mainly at the step of conversion from benign papillomas to malignant carcinomas. C1 NCI, DIFFERENTIAT CONTROL SECT, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. BIOCON INC, ROCKVILLE, MD 20855 USA. NR 20 TC 26 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1994 VL 15 IS 10 BP 2383 EP 2386 DI 10.1093/carcin/15.10.2383 PG 4 WC Oncology SC Oncology GA PM733 UT WOS:A1994PM73300050 PM 7955082 ER PT J AU LYSZ, TW ARORA, JK LIN, CR ZELENKA, PS AF LYSZ, TW ARORA, JK LIN, CR ZELENKA, PS TI 12(S)-HYDROXYEICOSATETRAENOIC ACID REGULATES DNA-SYNTHESIS AND PROTOONCOGENE EXPRESSION INDUCED BY EPIDERMAL GROWTH-FACTOR AND INSULIN IN RAT LENS EPITHELIUM SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CELL-CYCLE PROGRESSION; MYC MESSENGER-RNA; SERUM-FREE MEDIUM; C-MYC; PROTO-ONCOGENE; 3T3 CELLS; 12-HYDROXYEICOSATETRAENOIC ACID; TRANSCRIPTIONAL ACTIVATION; ENDOTHELIAL-CELLS; CHAIN-REACTION AB Neonatal rat lens epithelium has a high 12(S)hydroxyeicosatetraenoic acid [12(S)-HETE] synthetic capacity, which decreases as epithelial cell proliferation decreases with age. To determine whether products of the 12-lipoxygenase pathway are involved in lens cell proliferation, we measured the effect of 12-lipoxygenase inhibitors on endogenous 12-HETE production, epidermal growth factor/insulin-stimulated DNA synthesis and protooncogene expression in cultured neonatal rat lens epithelial cells. Incubation of neonatal rat lenses in epidermal growth factor plus insulin, which stimulated endogenous 12-HETE production 8- to 10-fold, also produced a transient induction of c-fos and c-myc mRNAs after 2 to 3 h, followed by a round of DNA synthesis approximately 20 h later. The lipoxygenase inhibitor, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, strongly inhibited both the endogenous 12-HETE synthesis and growth factor-stimulated DNA synthesis with a half-maximal inhibition between 10 and 20 mu M Cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (10 mu M) also inhibited the expression of c-fos and c-myc mRNA and, to a lesser extent, c-jun mRNA. The inhibitory effects of cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate on protooncogene expression and DNA synthesis were prevented by 0.3 mu M 12(S)-HETE but not by equivalent concentrations of either 5(S)-HETE or 15(S)-HETE. These findings suggest that endogenously synthesized 12(S)-HETE may mediate epidermal growth factor/insulin-stimulated DNA synthesis in neonatal rat lens epithelial cells by regulating protooncogene expression. C1 NEI,BETHESDA,MD 20892. RP LYSZ, TW (reprint author), UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT SURG,ROOM G-503,185 S ORANGE AVE,NEWARK,NJ 07103, USA. NR 59 TC 18 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1994 VL 5 IS 10 BP 1069 EP 1076 PG 8 WC Cell Biology SC Cell Biology GA PK595 UT WOS:A1994PK59500006 PM 7848908 ER PT J AU FUKASAWA, K MURAKAMI, MS BLAIR, DG KURIYAMA, R HUNT, T FISCHINGER, P VANDEWOUDE, GF AF FUKASAWA, K MURAKAMI, MS BLAIR, DG KURIYAMA, R HUNT, T FISCHINGER, P VANDEWOUDE, GF TI SIMILARITIES BETWEEN SOMATIC-CELLS OVEREXPRESSING THE MOS ONCOGENE AND OOCYTES DURING MEIOTIC INTERPHASE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MURINE SARCOMA-VIRUS; MICROTUBULE-ORGANIZING CENTERS; ACTIVATED PROTEIN-KINASE; SERINE THREONINE KINASES; XENOPUS-OOCYTES; MAP KINASE; MAMMALIAN FIBROBLASTS; MONOCLONAL-ANTIBODIES; 3T3 CELLS; MATURATION AB The mos protooncogene encodes a serine/threonine kinase and is a key regulator of oocyte meiotic maturation. After acute infection of Swiss 3T3 cells with virus containing the v-mos oncogene, cells expressing high levels of v-Mos round up and detach from the monolayer (floating cells), while cells that remain attached express 10-fold lower levels of v-Mos and are transformed. The floating cells are growth arrested with their chromosomes partially condensed in the absence of histone H1 kinase activity, while mitogen-activated protein kinase activity is very high. Collectively, these properties are similar to properties observed in maturing oocytes between meiosis I and II. In v-mos-transformed cell populations, mitogen-activated protein kinase activity is also elevated, correlating with the degree of morphological transformation and the level of Mos expression. Moreover, phosphoprotein modifications specific for M are found in both the floating cells and in v-mos-transformed cells, regardless of their cell cycle stage. One explanation for both morphological transformation and the phenotypes of the floating cells is that Mos imposes a meiotic program on different stages of the somatic cell cycle. The extent of this meiotic phenotype is proportional to the level of v-Mos expression. These results suggest that both morphological transformation and the phenotypes of the floating cells induced by Mos in Swiss 3T3 cells are related to its normal activities during oocyte maturation. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702. UNIV MINNESOTA,SCH MED,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. IMPERIAL CANC RES FUND,CLARE HALL LABS,S MIMMS EN6 3LD,HERTS,ENGLAND. MED UNIV S CAROLINA,CHARLESTON,SC 29425. FU NCI NIH HHS [N01-CO-74101] NR 79 TC 19 Z9 20 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 OCT PY 1994 VL 5 IS 10 BP 1093 EP 1103 PG 11 WC Cell Biology SC Cell Biology GA PK595 UT WOS:A1994PK59500009 PM 7848911 ER PT J AU MCCLOSKEY, P PIERCE, J KOSKI, RA VARNUM, B LIU, ET AF MCCLOSKEY, P PIERCE, J KOSKI, RA VARNUM, B LIU, ET TI ACTIVATION OF THE AXL RECEPTOR TYROSINE KINASE INDUCES MITOGENESIS AND TRANSFORMATION IN 32D CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; HEMATOPOIETIC PROGENITOR-CELL; SIGNAL-TRANSDUCTION; EGF RECEPTOR; GRANULOCYTIC DIFFERENTIATION; MYELOID-LEUKEMIA; EXPRESSION; ONCOGENES; PDGF; LINE AB axl is a transforming receptor tyrosine kinase isolated from DNA of patients with chronic myelogenous leukemia. Association of axl expression with myelogenous leukemias and its expression in primitive hematopoietic cells suggests a role for axl in myeloid biology. To study the cellular function of axl, we constructed a chimeric receptor tyrosine kinase composed of the extracellular and transmembrane domains of the EGF receptor and the cytoplasmic domain of axl; this chimera was named EAK for EGFR-Axl-Kinase. The EAK chimeric receptor was expressed in the mouse myeloid progenitor cell line 32D, which is dependent on interleukin 3 (IL-3) for proliferation and survival. Treatment of the 32D-EAK cells with EGF stimulated the tyrosine phosphorylation of the axl kinase domain and enabled proliferation through EGF rather than IL-3. Thus, axl can effectively couple with mitogenic signaling pathways intrinsic to 32D myeloid cells. Assay of proteins phosphorylated in response to different cytokine treatments showed that IL-3 and EGF exposure produced unique profiles in the 32D-EAK cells. Furthermore, jak-2 is phosphorylated only in response to IL-3 treatment in these cells. This suggests that IL-3 receptor and axl transduce mitogenic signals through separate pathways. In addition, exposure of cells expressing the chimeric receptor to EGF for 19 days converted the cells to factor-independent growth, a phenomenon not seen with other receptor tyrosine kinases. Generation of this transformed phenotype is absolutely dependent on axl activation by foster ligand. The tyrosine phosphorylation level of the axl kinase domain in the factor-independent subclones is 40-fold greater than the factor-dependent cells. The association of a unique axl phosphorylation level with the factor-independent phenotype suggests that there is a threshold phosphorylation level of the axl kinase for transformation. The fact that activation of the axl receptor leads to transformation of 32D cells suggests that axl can play a role in leukemic conversion of myeloid cells, either through inappropriate expression or improper activation. C1 UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD. AMGEN CORP,THOUSAND OAKS,CA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [R0I-CA49240-05] NR 30 TC 35 Z9 35 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 OCT PY 1994 VL 5 IS 10 BP 1105 EP 1117 PG 13 WC Cell Biology SC Cell Biology GA PK595 UT WOS:A1994PK59500010 PM 7848912 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI OXIDATION OF 1,1-DIMETHYLHYDRAZINE (UDMH) IN AQUEOUS-SOLUTION WITH AIR AND HYDROGEN-PEROXIDE SO CHEMOSPHERE LA English DT Article ID HYDRAZINES; NITROSAMINES; MUTAGENICITY; DESTRUCTION AB The degradation of 1,1-dimethylhydrazine (UDMH), a component of some rocket fuels, was investigated using atmospheric oxygen and hydrogen peroxide. The reactions were carried out in the presence and absence of copper catalysis and at varying pH. Reactions were also carried out in the presence of hydrazine, a constituent, along with UDMH, of the rocket fuel Aerozine-50. In the presence of copper, UDMH was degraded by air passed through the solution; the efficiency of degradation increased as the pH increased but the carcinogen N-nitrosodimethylamine (NDMA) was formed at neutral and alkaline pH. Oxidation was not seen in the absence of copper. Production of NDMA occurred even at copper concentrations of < 1 ppm. Oxidation of UDMH with hydrogen peroxide also gave rise to NDMB. When copper was absent degradation of UDMH did not occur at acid pH but when copper was present some degradation occurred at all pH levels investigated. The production of NDMA occurred mostly at neutral and alkaline pH. In general, higher concentrations of hydrogen peroxide and copper favored the production of NDMA. Dimethylamine, methanol, formaldehyde dimethylhydrazone, formaldehyde hydrazone, and tetramethyltetrazene were also produced. The last three compounds were tested and found to be mutagenic. RP LUNN, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ENVIRONM CONTROL & RES PROGRAM,POB B,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-74102] NR 26 TC 24 Z9 30 U1 2 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD OCT PY 1994 VL 29 IS 7 BP 1577 EP 1590 DI 10.1016/0045-6535(94)90287-9 PG 14 WC Environmental Sciences SC Environmental Sciences & Ecology GA PK804 UT WOS:A1994PK80400016 PM 7953474 ER PT J AU RADKEYARROW, M ZAHNWAXLER, C RICHARDSON, DT SUSMAN, A MARTINEZ, P AF RADKEYARROW, M ZAHNWAXLER, C RICHARDSON, DT SUSMAN, A MARTINEZ, P TI CARING BEHAVIOR IN CHILDREN OF CLINICALLY DEPRESSED AND WELL MOTHERS SO CHILD DEVELOPMENT LA English DT Article ID SEX-DIFFERENCES; YOUNG-CHILDREN; EMPATHY; PSYCHOPATHOLOGY; DISTRESS; SEVERITY; PARENTS; WOMEN; RISK AB Young children's sensitivity and responsiveness to mothers' needs were investigated under conditions of high and low parenting risk (depressed and nondepressed mothers, SADS-L). Child characteristics of gender, affect, and impulse control problems and the mother-child attachment relationship were examined as they related to children's caring actions. Children's caring behavior was observed in an experimental situation in which their mothers simulated sadness and in a naturalistic setting. Attachment alone and child's problems alone were not predictors, and maternal diagnosis alone was not a strong predictor. Girls were significantly more caring than boys. Severe maternal depression was necessary to bring out high levels of responding in boys. Highest frequencies of caring were from children with severely depressed mothers, problems of affect regulation, and secure attachment. The importance of recognizing interacting influences and diverse underlying processes in the development of children's caring behavior is discussed. RP RADKEYARROW, M (reprint author), NIMH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 59 Z9 59 U1 2 U2 13 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD OCT PY 1994 VL 65 IS 5 BP 1405 EP 1414 DI 10.1111/j.1467-8624.1994.tb00825.x PG 10 WC Psychology, Educational; Psychology, Developmental SC Psychology GA PR017 UT WOS:A1994PR01700011 PM 7982358 ER PT J AU NUSSBACHER, A SCHULMAN, SP FLEG, JL OCONNOR, F GLOTH, ST TOWNSEND, SN LAKATTA, EG GERSTENBLITH, G AF NUSSBACHER, A SCHULMAN, SP FLEG, JL OCONNOR, F GLOTH, ST TOWNSEND, SN LAKATTA, EG GERSTENBLITH, G TI DECREASING CENTRAL ARTERIAL STIFFNESS ELIMINATES AGE-DIFFERENCES IN CARDIAC EJECTION DURING MAXIMAL EXERCISE SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 15 EP 15 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700113 ER PT J AU SHARIR, T FLEG, J KASS, DA AF SHARIR, T FLEG, J KASS, DA TI MECHANISM OF ABNORMAL EJECTION FRACTION RESPONSE TO EXERCISE IN PATIENTS WITH MODERATE HYPERTENSION SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 90 IS 4 BP 15 EP 15 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700112 ER PT J AU XIAO, RP HOHL, CM ALTSCHULD, RA JONES, L LIVINGSTON, B ZIMAN, B TANTINI, B AF XIAO, RP HOHL, CM ALTSCHULD, RA JONES, L LIVINGSTON, B ZIMAN, B TANTINI, B TI THE BETA-2-ADRENOCEPTOR STIMULATED INCREASE IN CAMP IS NOT COUPLED TO CHANGES IN CA2+ DYNAMICS OR PHOSPHOLAMBAN PHOSPHORYLATION SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. OHIO STATE UNIV,COLUMBUS,OH 43210. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 39 EP 39 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700237 ER PT J AU DOMANSKI, MJ SLOAS, MM FOLLMANN, DA SCALISE, PP TUCKER, EE EGAN, D PIZZO, PA AF DOMANSKI, MJ SLOAS, MM FOLLMANN, DA SCALISE, PP TUCKER, EE EGAN, D PIZZO, PA TI EFFECT OF ZIDOVUDINE AND DIDANOSINE TREATMENT ON CARDIAC-FUNCTION IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 49 EP 49 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700297 ER PT J AU SHAMBUREK, RD ZECH, LA MEYN, S KINDT, M TALLEY, G HEDRICK, C CASTELLANI, L BREWER, HB AF SHAMBUREK, RD ZECH, LA MEYN, S KINDT, M TALLEY, G HEDRICK, C CASTELLANI, L BREWER, HB TI APOA-I AND APOA-II METABOLISM IN TRANSGENIC MICE OVEREXPRESSING APOA-II SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 81 EP 81 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700470 ER PT J AU VAISMAN, B KLEIN, HG BERARD, A ROUIS, M TALLEY, G MARCOVINA, S HOEG, JM HOYT, R BREWER, HB SANTAMARINAFOJO, S AF VAISMAN, B KLEIN, HG BERARD, A ROUIS, M TALLEY, G MARCOVINA, S HOEG, JM HOYT, R BREWER, HB SANTAMARINAFOJO, S TI HUMAN LCAT OVEREXPRESSION IN TRANSGENIC MICE - EFFECT ON PLASMA HDL LEVELS AND POTENTIAL ROLE IN REVERSE CHOLESTEROL TRANSPORT SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MDB,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. RI Rouis, Mustapha/E-4993-2016 NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 81 EP 81 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700472 ER PT J AU BERARD, A SHAMBUREK, RD VAISMAN, B MEYN, S KINDT, M ALBERS, J SANTAMARINAFOJO, S BREWER, HB AF BERARD, A SHAMBUREK, RD VAISMAN, B MEYN, S KINDT, M ALBERS, J SANTAMARINAFOJO, S BREWER, HB TI DIFFERENTIAL DIETARY-RESPONSE OF MICE OVEREXPRESSING HLCAT SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 82 EP 82 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700473 ER PT J AU KITSIOU, AN BARTLETT, ML BACHARACH, SL RAINA, A DILSIZIAN, V AF KITSIOU, AN BARTLETT, ML BACHARACH, SL RAINA, A DILSIZIAN, V TI THE MAGNITUDE OF F-18 FLUORODEOXYGLUCOSE UPTAKE AND NOT O-15-WATER DIFFERENTIATES RECOVERY OF ASYNERGIC REGIONS AFTER REVASCULARIZATION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 113 EP 113 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700644 ER PT J AU CAPE, EG JONES, M MANDULEY, R SOLOWLEJCZYK, D KELLY, D YAMADA, I VALDESCRUZ, LM AF CAPE, EG JONES, M MANDULEY, R SOLOWLEJCZYK, D KELLY, D YAMADA, I VALDESCRUZ, LM TI PRESSURE RECOVERY VISCOUS EFFECT EQUILIBRIUM CONTROLS DOPPLER PREDICTION OF PRESSURE-GRADIENTS IN BILEAFLET MECHANICAL VALVES SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. NHLBI,LAMS,BETHESDA,MD 20892. COLUMBIA UNIV,NEW YORK,NY 10027. MAIMONIDES HOSP,BROOKLYN,NY 11219. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 115 EP 115 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700652 ER PT J AU KASHYAP, V SANTAMARINAFOJO, S BROWN, D APPLEBAUMBOWDEN, D MEYN, S PARROTT, C MAEDA, N BREWER, HB AF KASHYAP, V SANTAMARINAFOJO, S BROWN, D APPLEBAUMBOWDEN, D MEYN, S PARROTT, C MAEDA, N BREWER, HB TI APOE DEFICIENCY - GENE REPLACEMENT USING ADENOVIRUS VECTORS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 134 EP 134 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700752 ER PT J AU DONG, G DICHEK, DA AF DONG, G DICHEK, DA TI REGULATED GENE-EXPRESSION IN ENDOTHELIAL-CELLS FOLLOWING ADENOVIRAL GENE-TRANSFER SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 140 EP 140 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700786 ER PT J AU JENKINS, GM CROW, M BILATO, C RYU, WS LI, ZH STETLERSTEVENSON, W NATER, C FROEHLICH, J LAKATTA, E CHENG, L AF JENKINS, GM CROW, M BILATO, C RYU, WS LI, ZH STETLERSTEVENSON, W NATER, C FROEHLICH, J LAKATTA, E CHENG, L TI THE EXPRESSION OF 72KD TYPE-IV COLLAGENASE AND ITS INHIBITOR (TIMP2) FOLLOWING VASCULAR INJURY SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 142 EP 142 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700797 ER PT J AU RYU, WS NOH, DY JENKINS, GM NATER, C LAKATTA, EG RHEE, SG CHENG, L AF RYU, WS NOH, DY JENKINS, GM NATER, C LAKATTA, EG RHEE, SG CHENG, L TI SELECTIVE INCREASES IN EXPRESSION OF PHOSPHOLIPASE-C ISOFORMS, PLC-GAMMA-1 AND PLC-DELTA-1, FOLLOWING BALLOON INJURY TO THE RAT CAROTID-ARTERY SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 142 EP 142 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700796 ER PT J AU BILATO, C PAULY, RR GLUZBAND, Y MONTICONE, R CROW, MT AF BILATO, C PAULY, RR GLUZBAND, Y MONTICONE, R CROW, MT TI BASIC FIBROBLAST GROWTH-FACTOR STIMULATES PLATELET-DERIVED GROWTH FACTOR-DIRECTED SMOOTH-MUSCLE CELL-MIGRATION BY ACTIVATING CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE-II SO CIRCULATION LA English DT Meeting Abstract C1 NIA,LCS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 145 EP 145 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700812 ER PT J AU PILI, R CHANG, J MUHLHAUSER, J BEWIG, B CRYSTAL, RG CAPOGROSSI, MC PASSANITI, A AF PILI, R CHANG, J MUHLHAUSER, J BEWIG, B CRYSTAL, RG CAPOGROSSI, MC PASSANITI, A TI ADENOVIRUS-MEDIATED GENE-TRANSFER OF ANGIOGENIC GROWTH-FACTORS AND BIOSAFETY - LACK OF INCREASED TUMORIGENICITY IN-VIVO SO CIRCULATION LA English DT Meeting Abstract C1 GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD. GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD. NHLBI,PULM BRANCH,BETHESDA,MD 20892. IDI,ROME,ITALY. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 147 EP 147 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700823 ER PT J AU ATIGA, WL MCAREAVEY, D FANANAPAZIR, L AF ATIGA, WL MCAREAVEY, D FANANAPAZIR, L TI FAILURE OF DDD PACING TO RELIEVE SYMPTOMS AND LV OUTFLOW OBSTRUCTION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY - INCIDENCE, MECHANISMS AND MANAGEMENT SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 171 EP 171 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700955 ER PT J AU SOLLOTT, SJ PAULY, RR CROW, MT BILATO, C ZIMAN, BD MONTICONE, R LAKATTA, EG AF SOLLOTT, SJ PAULY, RR CROW, MT BILATO, C ZIMAN, BD MONTICONE, R LAKATTA, EG TI VASCULAR SMOOTH-MUSCLE CELL-DIFFERENTIATION ALTERS PDGF CA2+-SIGNALING SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GRC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 190 EP 190 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701055 ER PT J AU BROWN, DR HOEG, JM SHAMBUREK, RD BROUSSEAU, ME TALLEY, GD SANTAMARINAFOJO, S BREWER, HB AF BROWN, DR HOEG, JM SHAMBUREK, RD BROUSSEAU, ME TALLEY, GD SANTAMARINAFOJO, S BREWER, HB TI ADENOVIRAL DELIVERY OF LDL RECEPTORS RAISES PLASMA APOLIPOPROTEIN-A-I CONCENTRATIONS BY DELAYING APOLIPOPROTEIN-A-I CATABOLISM SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MDB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 240 EP 240 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701323 ER PT J AU CONRAD, CH BOLUYT, MO BROOKS, WW ONEILL, L CHALETSKY, DM ROBINSON, KG BING, OHL AF CONRAD, CH BOLUYT, MO BROOKS, WW ONEILL, L CHALETSKY, DM ROBINSON, KG BING, OHL TI EFFECT OF CAPTOPRIL ON TGF-BETA GENE-EXPRESSION, MYOCARDIAL STIFFNESS, AND FIBROSIS IN THE SPONTANEOUSLY HYPERTENSIVE RAT SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. VET ADM MED CTR JAMAICA PLAIN,BOSTON,MA 02130. NIA,GRC,BALTIMORE,MD 21224. NR 0 TC 3 Z9 3 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 OCT PY 1994 VL 90 IS 4 BP 261 EP 261 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701436 ER PT J AU OCONNOR, FC FLEG, JL GOLDBERG, A LAKATTA, L SCHULMAN, S AF OCONNOR, FC FLEG, JL GOLDBERG, A LAKATTA, L SCHULMAN, S TI EFFECT OF OBESITY ON CARDIOVASCULAR PERFORMANCE DURING MAXIMAL CYCLE EXERCISE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. US VET ADM,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 273 EP 273 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701500 ER PT J AU ZUKOWSKAGROJEC, Z BERGESON, S KLEINMAN, H GRANT, D AF ZUKOWSKAGROJEC, Z BERGESON, S KLEINMAN, H GRANT, D TI NEUROPEPTIDE-Y (NPY) - A NOVEL MITOGENIC AND ANGIOGENIC FACTOR SO CIRCULATION LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL,WASHINGTON,DC 20007. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 290 EP 290 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701593 ER PT J AU FREDMAN, J PAULY, RR STERN, D SCHMIDT, AM YAN, SD BRETT, J MONTICONE, R CROW, MT AF FREDMAN, J PAULY, RR STERN, D SCHMIDT, AM YAN, SD BRETT, J MONTICONE, R CROW, MT TI ADVANCED GLYCATION ENDPRODUCTS INTERACTING WITH THEIR RECEPTORS ACTIVATE VASCULAR SMOOTH-MUSCLE CELLS - INDUCTION OF CHEMOATTRACTANTS FOR SMOOTH-MUSCLE CELLS AND MONOCYTES SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. COLUMBIA UNIV COLL PHYS & SURG,DEPT PHYSIOL BIOPHYS,NEW YORK,NY 10032. NR 0 TC 3 Z9 3 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 291 EP 291 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701599 ER PT J AU GUZMAN, RJ HERSHKOWITZ, E BRODY, S CRYSTAL, RG EPSTEIN, SE FINKEL, T AF GUZMAN, RJ HERSHKOWITZ, E BRODY, S CRYSTAL, RG EPSTEIN, SE FINKEL, T TI INHIBITION OF IN-VIVO NEOINTIMAL PROLIFERATION USING ADENOVIRAL GENE-TRANSFER OF THE HERPES-SIMPLEX THYMIDINE KINASE GENE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,CARDIOL & PULM BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 292 EP 292 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701601 ER PT J AU JENKINS, GM LEONG, K HELLER, P SOLLOTT, S KINSELLA, J NATER, C OCONNOR, F FROEHLICH, J CHENG, L AF JENKINS, GM LEONG, K HELLER, P SOLLOTT, S KINSELLA, J NATER, C OCONNOR, F FROEHLICH, J CHENG, L TI LOCAL-DELIVERY OF TAXOL INHIBITS NEOINTIMAL REGROWTH FOLLOWING BALLOON INJURY OF THE RAT CAROTID-ARTERY SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOMED ENGN,BALTIMORE,MD 21205. NR 0 TC 1 Z9 1 U1 0 U2 6 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 297 EP 297 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701628 ER PT J AU CORDA, S SPURGEON, HA CAPOGROSSI, MC ZIEGELSTEIN, RC AF CORDA, S SPURGEON, HA CAPOGROSSI, MC ZIEGELSTEIN, RC TI DISTINCT RYANODINE-SENSITIVE AND CAFFEINE-SENSITIVE CALCIUM POOLS IN HUMAN ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 302 EP 302 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701656 ER PT J AU DILSIZIAN, V QUIGG, FJ SHIRANI, J LEE, J ALAVI, K PICK, R BACHARACH, SL AF DILSIZIAN, V QUIGG, FJ SHIRANI, J LEE, J ALAVI, K PICK, R BACHARACH, SL TI HISTOMORPHOLOGIC VALIDATION OF THALLIUM REINJECTION AND FLUORODEOXYGLUCOSE PET FOR ASSESSMENT OF MYOCARDIAL VIABILITY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 90 IS 4 BP 314 EP 314 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701721 ER PT J AU QUYYUMI, AA DAKAK, N ANDREWS, NP HUSAIN, S ARORA, S JOHNSON, G MINCEMOYER, R PANZA, JA CANNON, RO AF QUYYUMI, AA DAKAK, N ANDREWS, NP HUSAIN, S ARORA, S JOHNSON, G MINCEMOYER, R PANZA, JA CANNON, RO TI NITRIC-OXIDE ACTIVITY IN HUMAN CORONARY ATHEROSCLEROSIS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 321 EP 321 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701757 ER PT J AU CHEN, YP OTOOLE, TE SHIPLEY, T FORSYTH, J LAFLAMME, SE YAMADA, KM SHATTIL, SJ GINSBERG, MH AF CHEN, YP OTOOLE, TE SHIPLEY, T FORSYTH, J LAFLAMME, SE YAMADA, KM SHATTIL, SJ GINSBERG, MH TI INSIDE-OUT SIGNAL-TRANSDUCTION INHIBITED BY ISOLATED INTEGRIN CYTOPLASMIC DOMAINS SO CIRCULATION LA English DT Meeting Abstract C1 SCRIPPS RES INST, LA JOLLA, CA USA. NIDR, BETHESDA, MD 20892 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 346 EP 346 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701893 ER PT J AU KUIPERS, F SMIT, JJM ELFERINK, RPJO OTTENHOF, R SCHINKEL, AH VERKADE, HJ VONK, RJ BORST, P GROEN, AK AF KUIPERS, F SMIT, JJM ELFERINK, RPJO OTTENHOF, R SCHINKEL, AH VERKADE, HJ VONK, RJ BORST, P GROEN, AK TI THE ROLE OF BILIARY CHOLESTEROL AND PHOSPHOLIPIDS IN THE REGULATION OF PLASMA-LIPID LEVELS - STUDIES IN MDR2 TRANSGENIC MICE SO CIRCULATION LA English DT Meeting Abstract C1 GRONINGEN INST DRUG STUDIES,GRONINGEN,NETHERLANDS. NCI,BETHESDA,MD 20892. UNIV AMSTERDAM,ACAD MED CTR,1105 AZ AMSTERDAM,NETHERLANDS. NR 1 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 352 EP 352 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701926 ER PT J AU ZIEGELSTEIN, RC BLANK, RS CHENG, L CAPOGROSSI, MC AF ZIEGELSTEIN, RC BLANK, RS CHENG, L CAPOGROSSI, MC TI AN ABRUPT DECREASE IN HEMODYNAMIC SHEAR-STRESS ENHANCES RECOVERY FROM INTRACELLULAR ACIDIFICATION IN VASCULAR ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 357 EP 357 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701955 ER PT J AU GAMBASSI, G CAPOGROSSI, MC AF GAMBASSI, G CAPOGROSSI, MC TI CYTOSOLIC PH RECOVERY FOLLOWING AN ACID LOAD IS DIFFERENTLY AFFECTED BY ALPHA(1) ADRENERGIC-RECEPTOR SUBTYPES VIA PKC-DEPENDENT MODULATION OF NA+/H+ EXCHANGE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 358 EP 358 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701957 ER PT J AU SHIRANI, J PICK, R QUIGG, RJ ROBERTS, WC DILSIZIAN, V AF SHIRANI, J PICK, R QUIGG, RJ ROBERTS, WC DILSIZIAN, V TI PATHOLOGICAL REMODELING OF NON-MYOCYTE COMPARTMENT IN CHRONIC ISCHEMIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 377 EP 377 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702061 ER PT J AU GE, SP JONES, M YAMADA, I AF GE, SP JONES, M YAMADA, I TI QUANTIFICATION OF FORWARD FLOW-THROUGH THE MITRAL-VALVE ORIFICE BY THE COLOR DOPPLER FLOW CONVERGENCE TECHNIQUE - STUDY OF A NEW ISOVELOCITY SURFACE METHOD IN AN ANIMAL-MODEL SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 381 EP 381 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702085 ER PT J AU PANZA, JA CURIEL, RV LAURIENZO, JM UNGER, EF AF PANZA, JA CURIEL, RV LAURIENZO, JM UNGER, EF TI THE NORMAL QUANTITATIVE MYOCARDIAL RESPONSE TO DOBUTAMINE IN HUMANS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 391 EP 391 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702138 ER PT J AU ANDREWS, NP DAKAK, N SCHENKE, WH QUYYUMI, AA AF ANDREWS, NP DAKAK, N SCHENKE, WH QUYYUMI, AA TI PLATELET-ENDOTHELIUM INTERACTIONS IN HUMANS - CHANGES IN PLATELET CYCLIC GUANOSINE-MONOPHOSPHATE CONTENT IN PATIENTS WITH ENDOTHELIAL DYSFUNCTION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 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 OCT PY 1994 VL 90 IS 4 BP 397 EP 397 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702171 ER PT J AU APPLEBAUMBOWDEN, D KOBAYASHI, J BROWN, D MEYN, S HOEG, JM PARROT, C WELCHIN, H MAEDA, N BREWER, HB SANTAMARINAFOJO, S AF APPLEBAUMBOWDEN, D KOBAYASHI, J BROWN, D MEYN, S HOEG, JM PARROT, C WELCHIN, H MAEDA, N BREWER, HB SANTAMARINAFOJO, S TI GENE REPLACEMENT OF A LIPOLYTIC ENZYME IN HL-DEFICIENT MICE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MDB,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 405 EP 405 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702210 ER PT J AU DUGI, KA FEUERSTEIN, IM SANTAMARINAFOJO, S BREWER, HB HOEG, JM AF DUGI, KA FEUERSTEIN, IM SANTAMARINAFOJO, S BREWER, HB HOEG, JM TI LIPOPROTEIN-LIPASE MAY CONTRIBUTE TO THE VARIANT DEGREE OF ATHEROSCLEROSIS IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 90 IS 4 BP 405 EP 405 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702209 ER PT J AU XIAO, RP HOHL, CM JI, XW ZIMAN, BD ALTSCHULD, RA LAKATTA, EG AF XIAO, RP HOHL, CM JI, XW ZIMAN, BD ALTSCHULD, RA LAKATTA, EG TI ADENOSINE ANTAGONIZES BETA(2)-ADRENOCEPTOR STIMULATED INCREASES IN THE CA(I) TRANSIENT AND CONTRACTION IN CANINE HEART-CELLS VIA A CAMP-INDEPENDENT MECHANISMS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RECH INST,BALTIMORE,MD 21224. OHIO STATE UNIV,DEPT MED BIOCHEM,COLUMBUS,OH 43210. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 414 EP 414 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702256 ER PT J AU FANANAPAZIR, L WINKLER, JB SATORIUS, C EPSTEIN, ND AF FANANAPAZIR, L WINKLER, JB SATORIUS, C EPSTEIN, ND TI IDENTIFICATION OF BETA-MYOSIN HEAVY-CHAIN GENE-MUTATIONS IN 31 ATHLETES WITH HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 442 EP 442 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702405 ER PT J AU RYSCHON, TW FOWLER, MD ARAI, AE WYSONG, RE MCAREAVEY, D EPSTEIN, ND FANANAPAZIR, L BALABAN, RS AF RYSCHON, TW FOWLER, MD ARAI, AE WYSONG, RE MCAREAVEY, D EPSTEIN, ND FANANAPAZIR, L BALABAN, RS TI MUSCLE ENERGETICS DURING DYNAMIC EXERCISE IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 90 IS 4 BP 442 EP 442 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702408 ER PT J AU FANANAPAZIR, L EPSTEIN, ND AF FANANAPAZIR, L EPSTEIN, ND TI RISK-EVALUATION, THERAPY, AND PROGNOSIS IN ATHLETES WITH HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 443 EP 443 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702414 ER PT J AU MCAREAVEY, D FANANAPAZIR, L AF MCAREAVEY, D FANANAPAZIR, L TI DDD PACING MAY OBVIATE THE NEED FOR INVESTIGATION OF SYMPTOMS OF IMPAIRED CONSCIOUSNESS IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 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 OCT PY 1994 VL 90 IS 4 BP 443 EP 443 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702410 ER PT J AU ZIEGELSTEIN, RC ZHENG, G MODDO, JM AVERSANO, T OUYANG, P AF ZIEGELSTEIN, RC ZHENG, G MODDO, JM AVERSANO, T OUYANG, P TI THE NADPH OXIDASE INHIBITOR DIPHENYLENEIODONIUM INHIBITS EDRF/NO IN RAT AORTA WITHOUT AFFECTING ENDOTHELIAL [CA2+] SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DIV CARDIOL,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 459 EP 459 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702498 ER PT J AU ZHOU, YF EPSTEIN, SE FINKEL, T AF ZHOU, YF EPSTEIN, SE FINKEL, T TI INCREASED SCAVENGER LDL RECEPTOR ACTIVITY IN RAT SMOOTH-MUSCLE CELLS FOLLOWING HUMAN CYTOMEGALOVIRUS-INFECTION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 462 EP 462 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702516 ER PT J AU MURPHY, E GLASGOW, W FRALIX, T STEENBERGEN, C AF MURPHY, E GLASGOW, W FRALIX, T STEENBERGEN, C TI LIPOXYGENASE METABOLITES AS MEDIATORS OF PRECONDITIONING IN THE RAT-HEART SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,DURHAM,NC 27706. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 478 EP 478 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702601 ER PT J AU LI, ZH CHENG, L JENKINS, GM SMIALEK, JE LI, L CROW, MT STETLERSTEVENSON, W FROEHLICH, J LAKATTA, EG AF LI, ZH CHENG, L JENKINS, GM SMIALEK, JE LI, L CROW, MT STETLERSTEVENSON, W FROEHLICH, J LAKATTA, EG TI LOCALIZATION AND QUANTIFICATION OF 72 KD TYPE-IV COLLAGENASE IN HUMAN SUBCLINICAL AORTIC ATHEROSCLEROTIC LESIONS AND IN THE NEOINTIMA OF RAT CAROTID-ARTERY AFTER DEENDOTHELIALIZATION SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 515 EP 515 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702805 ER PT J AU PILI, R MUHLHAUSER, J MERRILL, MJ MAEDA, H CHANG, J PASSANITI, A BEWIG, B CRYSTAL, RG CAPOGROSSI, MC AF PILI, R MUHLHAUSER, J MERRILL, MJ MAEDA, H CHANG, J PASSANITI, A BEWIG, B CRYSTAL, RG CAPOGROSSI, MC TI ANGIOGENESIS INDUCED BY ADENOVIRUS-MEDIATED GENE-TRANSFER OF SECRETED AND NON-SECRETED FORMS OF ACIDIC FIBROBLAST GROWTH-FACTOR SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NIA,BIOL CHEM LAB,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 516 EP 516 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702810 ER PT J AU SCHULICK, AH NEWMAN, KD DICHEK, DA AF SCHULICK, AH NEWMAN, KD DICHEK, DA TI A THERAPEUTIC WINDOW FOR IN-VIVO ADENOVIRAL VECTOR-MEDIATED GENE-TRANSFER SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 2 TC 2 Z9 2 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 OCT PY 1994 VL 90 IS 4 BP 516 EP 516 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702811 ER PT J AU SCHULICK, AH DONG, G NEWMAN, KD VIRMANI, R DICHEK, DA AF SCHULICK, AH DONG, G NEWMAN, KD VIRMANI, R DICHEK, DA TI IN-VIVO ENDOTHELIAL-SPECIFIC ADENOVIRAL VECTOR-MEDIATED GENE-TRANSFER SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 517 EP 517 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702813 ER PT J AU PANZA, JA CURIEL, RV LAURIENZO, JM QUYYUMI, AA DILSIZIAN, V AF PANZA, JA CURIEL, RV LAURIENZO, JM QUYYUMI, AA DILSIZIAN, V TI ISCHEMIC THRESHOLD MEASURED DURING TRANSESOPHAGEAL DOBUTAMINE STRESS ECHOCARDIOGRAPHY CORRELATES WITH KNOWN INDEXES OF POOR-PROGNOSIS IN CORONARY-ARTERY DISEASE SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 560 EP 560 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703047 ER PT J AU NUSSBACHE, A FLEG, JL SCHULMAN, SP OCONNOR, F GLOTH, ST LIMA, JAC TOWNSEND, SN GERSTENBLITH, G AF NUSSBACHE, A FLEG, JL SCHULMAN, SP OCONNOR, F GLOTH, ST LIMA, JAC TOWNSEND, SN GERSTENBLITH, G TI AGE-RELATED MECHANISMS OF VASODILATOR BLOOD-PRESSURE REDUCTION SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 565 EP 565 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703078 ER PT J AU KEON, CA TUSCHIYA, N KASHIWAYA, Y SATO, K CLARKE, K RADDA, GK VEECH, RL AF KEON, CA TUSCHIYA, N KASHIWAYA, Y SATO, K CLARKE, K RADDA, GK VEECH, RL TI SUBSTRATE DEPENDENCE OF THE MITOCHONDRIAL-MEMBRANE POTENTIAL IN THE ISOLATED WORKING RAT-HEART SO CIRCULATION LA English DT Meeting Abstract C1 UNIV OXFORD,DEPT BIOCHEM,OXFORD,ENGLAND. NIAAA,METAB LAB,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 630 EP 630 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703422 ER PT J AU PAULY, RC MONTICONE, R FREDMAN, J BILATO, C SOLLOTT, SJ JENKINS, M CHENG, L LAKATTA, EG CROW, MT AF PAULY, RC MONTICONE, R FREDMAN, J BILATO, C SOLLOTT, SJ JENKINS, M CHENG, L LAKATTA, EG CROW, MT TI DIFFERENCES IN THE MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS CULTURED FROM THE NEOINTIMA AND MEDIA OF RAT CAROTID ARTERIES SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 652 EP 652 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703540 ER PT J AU CUOCOLO, A PERRONEFILARDI, P MARON, BJ BONOW, RO AF CUOCOLO, A PERRONEFILARDI, P MARON, BJ BONOW, RO TI IMPAIRED DIASTOLIC FILLING AND SYSTOLIC DYSFUNCTION DURING EXERCISE IN HYPERTENSIVE PATIENTS WITHOUT LEFT-VENTRICULAR HYPERTROPHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 90 IS 4 BP 656 EP 656 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703561 ER PT J AU LENFANT, C AF LENFANT, C TI REPORT OF THE NHLBI-WORKING-GROUP ON RESEARCH IN CORONARY HEART-DISEASE IN BLACKS SO CIRCULATION LA English DT Editorial Material DE CARDIOVASCULAR NEWS; RACE; HEART DISEASE; RISK FACTORS ID RACIAL-DIFFERENCES; UNITED-STATES; RISK-FACTORS; WHITE MEN; MORTALITY; POPULATION; PATTERNS; SURGERY; RATES; WOMEN RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 42 TC 13 Z9 13 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 1613 EP 1623 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PM632 UT WOS:A1994PM63200002 PM 7923643 ER PT J AU LEVY, D SALOMON, M DAGOSTINO, RB BELANGER, AJ KANNEL, WB AF LEVY, D SALOMON, M DAGOSTINO, RB BELANGER, AJ KANNEL, WB TI PROGNOSTIC IMPLICATIONS OF BASE-LINE ELECTROCARDIOGRAPHIC FEATURES AND THEIR SERIAL CHANGES IN SUBJECTS WITH LEFT-VENTRICULAR HYPERTROPHY SO CIRCULATION LA English DT Article DE FRAMINGHAM HEART STUDY; HYPERTROPHY; ELECTROCARDIOGRAPHY; MORBIDITY; MORTALITY ID CORONARY-ARTERY DISEASE; HYPERTENSIVE HEART-DISEASE; PATHOPHYSIOLOGIC ASSESSMENT; CRITERIA; ARRHYTHMIAS; RISK; PREVALENCE; MORTALITY; MASS; VALIDATION AB Background During the past half-century, the ECG has been used extensively for the diagnosis of left ventricular hypertrophy. Persons with ECG evidence of left ventricular hypertrophy are at increased risk for the development of cardiovascular disease. Methods and Results Subjects from the Framingham Heart Study with ECG evidence of left ventricular hypertrophy were eligible for this investigation if they were free of cardiovascular disease and did not have complete bundle-branch block or Wolff-Parkinson-White syndrome. Logistic regression analyses of pooled biennial examinations were used to determine risk for cardiovascular disease as a function of baseline voltage (sum of R wave in aVL plus S wave in V-3) and repolarization and as a function of serial changes in these ECG features of hypertrophy. The eligible sample consisted of 274 men (mean age, 60 years) and 250 women (mean age, 64 years) who contributed 2660 person-examinations. During follow-up, there were 269 new cardiovascular events. Compared with subjects in the first guartile of voltage at baseline, the age-adjusted odds ratio for cardiovascular disease among subjects in the fourth quartile was 3.08 (95% confidence interval [CI], 1.87 to 5.07) in men and 3.29 (95% CI, 1.78 to 6.09) in women. Compared with a normal repolarization pattern, the presence of severe repolarization abnormalities was associated with an age-adjusted odds ratio of 5.84 (95% CI, 3.55 to 9.62) in men and 2.47 (95% CI, 1.38 to 4.42) in women. Subjects with a serial decline in voltage were at lower risk for cardiovascular disease than were those with no serial change (men: odds ratio after adjusting for age and baseline voltage, 0.46; 95% CI, 0.26 to 0.84; women: odds ratio, 0.56; 95% CI, 0.30 to 1.04). In contrast, those with a serial increase in voltage were at greater risk for cardiovascular disease (men: odds ratio, 1.86; 95% CI, 1.14 to 3.03; women: odds ratio, 1.61; 95% CI, 0.91 to 2.84). Compared with those with no serial change, an improvement in repolarization was associated with a marginally significant reduction in cardiovascular risk in men (odds ratio after adjusting for age and baseline repolarization, 0.45; 95% CI, 0.20 to 1.01). Worsening of repolarization was associated with increased risk for cardiovascular disease in both sexes (men: odds ratio, 1.89; 95% CI, 1.05 to 3.40; women: odds ratio, 2.02; 95% CI, 1.07 to 3.81). Conclusions The results of this investigation suggest that regression of ECG features of left ventricular hypertrophy confers an improvement in risk for cardiovascular disease, whereas serial worsening imposes increased risk. The benefits to be derived from regression of left ventricular hypertrophy must be confirmed in other clinical settings. C1 NHLBI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,DIV EPIDEMIOL & PREVENT MED,BOSTON,MA. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV EPIDEMIOL,BOSTON,MA 02215. RP LEVY, D (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. NR 44 TC 421 Z9 434 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 OCT PY 1994 VL 90 IS 4 BP 1786 EP 1793 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PM632 UT WOS:A1994PM63200023 PM 7923663 ER PT J AU ZIEGELSTEIN, RC CORDA, S PILI, R PASSANITI, A LEFER, D ZWEIER, JL FRATICELLI, A CAPOGROSSI, MC AF ZIEGELSTEIN, RC CORDA, S PILI, R PASSANITI, A LEFER, D ZWEIER, JL FRATICELLI, A CAPOGROSSI, MC TI INITIAL CONTACT AND SUBSEQUENT ADHESION OF HUMAN NEUTROPHILS OR MONOCYTES TO HUMAN AORTIC ENDOTHELIAL-CELLS RELEASES AN ENDOTHELIAL INTRACELLULAR CALCIUM STORE SO CIRCULATION LA English DT Article DE ENDOTHELIUM; LEUKOCYTES; INDO 1; SHEAR STRESS ID PLATELET-ACTIVATING-FACTOR; POLYMORPHONUCLEAR LEUKOCYTES; VONWILLEBRAND-FACTOR; CYTOSOLIC CALCIUM; ADHERENCE; MONOLAYERS; HISTAMINE; RECEPTOR; CA-2+; CD18 AB Background Increases in both leukocyte and endothelial cytosolic free [Ca2+] may be involved in intercellular adhesion by regulating the affinity of surface adhesion molecules or by facilitating transendothelial leukocyte migration. The purpose of this study was to examine the effect of initial contact and subsequent adhesion of human neutrophils or monocytes on human aortic endothelial [Ca2+]. Methods and Results Endothelial monolayers were loaded with the fluorescent Ca2+ indicator indo 1 and exposed to isolated human peripheral blood neutrophils or to a cultured human monocyte cell line. A rapid, fourfold to fivefold increase in endothelial cytosolic [Ca2+] occurred within seconds of leukocyte contact. No increase in endothelial [Ca2+] occurred on contact of 18.25-mu m inert microspheres, isolated red blood cells, or suspensions of cultured human aortic endothelial cells. In experiments performed on monolayers grown in 1-mm(2) capillary flow tubes, the increase in endothelial cytosolic [Ca2+] On initial leukocyte contact was found to be related to the subsequent resistance to leukocyte detachment during exposure to arterial levels of shear stress (13.4 dyne.cm(-2)). The increase in endothelial cytosolic [Ca2+] during leukocyte contact was not inhibited in Ca2+-free buffer but was abolished by prior depletion of an endoplasmic reticulum Ca2+ store by thapsigargin. Pretreatment of neutrophils with R15.7, a specific monoclonal antibody to the adhesion protein CD-18, inhibited the increase in endothelial cytosolic [Ca2+] on neutrophil contact. Conclusions Initial contact leading to subsequent adhesion of human leukocytes to human aortic endothelial cells releases an endothelial intracellular Ca2+ store. This may, in part, be mediated by specific adhesion proteins and may in turn regulate the affinity of surface adhesion molecules or facilitate transendothelial migration of leukocytes. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. INRCA ANCONA,CARDIOL SPERIMENTALE LAB,ANCONA,ITALY. RP ZIEGELSTEIN, RC (reprint author), JOHS HOPKINS BAYVIEW MED CTR,DIV CARDIOL,CARDIOL B-1 S,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Lefer, David/A-6372-2012 NR 38 TC 37 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 OCT PY 1994 VL 90 IS 4 BP 1899 EP 1907 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PM632 UT WOS:A1994PM63200038 PM 7923678 ER PT J AU GUZMAN, RJ HERSHKOWITZ, E BRODY, S CRYSTAL, RG EPSTEIN, SE FINKEL, T AF GUZMAN, RJ HERSHKOWITZ, E BRODY, S CRYSTAL, RG EPSTEIN, SE FINKEL, T TI INHIBITION OF IN-VIVO NEOINTIMAL PROLIFERATION USING ADENOVIRAL GENE-TRANSFER OF THE HERPES-SIMPLEX THYMIDINE KINASE GENE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,CARDIOL & PULM BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP OI EP PI PN 2 PG 0 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700042 ER PT J AU BERNSTEIN, KA KAHL, LE BALOW, JE LEFKOWITH, JB AF BERNSTEIN, KA KAHL, LE BALOW, JE LEFKOWITH, JB TI SEROLOGIC MARKERS OF LUPUS NEPHRITIS IN PATIENTS - USE OF A TISSUE-BASED ELISA AND EVIDENCE FOR IMMUNOPATHOGENIC HETEROGENEITY SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE LUPUS; GLOMERULONEPHRITIS; ANTI-DNA ID ANTI-DNA ANTIBODIES; FORM IMMUNE DEPOSITS; RENAL-DISEASE; ERYTHEMATOSUS; MURINE; COMPLEXES; MICE; AUTOANTIBODIES; SERUM; BIND AB In order to assess the ability of various serologic assays to correlate with lupus nephritis, we analysed sera obtained from 60 patients with systemic lupus erythematosus (SLE). Patients were categorized as having active nephritis (group 1), active lupus without nephritis (group 2), inactive lupus with prior nephritis (group 3), or inactive lupus without prior nephritis (group 4). Three parameters were assessed including anti-dsDNA antibodies (Farr assay), immune complexes (Clq binding), and anti-Clq antibodies (salt-stable Clq binding). Additionally, glomerular binding activity (GBA) was measured using a new solid-phase immunoassay that detects immune elements by their ability to bind glomerular tissue. We found that patients with nephritis(group 1) exhibited higher mean values for each assay than patients in each of the other three groups (P = 0.001, 0.009, 0.14, and 0.23 in the GBA, Clq, anti-dsDNA, and anti-Clq assays, respectively). The only assay which distinguished patients with nephritis (group 1) from patients having active disease without nephritis (group 2) was the GBA (mean 0.48 +/- 0.09 versus 0.15 +/- 0.04, P < 0.05). In terms of utility, ail tests were specific for diagnosing nephritis among patients with lupus; however, only the GBA was reasonably sensitive. The information provided by the anti-dsDNA and Clq assays were not correlated with one another, nor additive to the GBA. Patients with false negative GBA tended to have received more intensive immunosuppression. The qualitative characteristics of GBA varied among patients with nephritis. These data suggest the pathogenesis of lupus nephritis is complex, and may be mediated by an array of immune elements. Moreover, the data indicate the potential utility for a broad tissue-based approach to detection of pathogenic immune elements over other, specific immunologic markers. C1 WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110. NIDDKD,BETHESDA,MD 20892. RP BERNSTEIN, KA (reprint author), WASHINGTON UNIV,SCH MED,DEPT MED,DIV RHEUMATOL,BOX 8045,ST LOUIS,MO 63110, USA. NR 41 TC 24 Z9 26 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 OCT PY 1994 VL 98 IS 1 BP 60 EP 65 PG 6 WC Immunology SC Immunology GA PJ844 UT WOS:A1994PJ84400011 PM 7923886 ER PT J AU VREMAN, HJ STEVENSON, DK OH, W FANAROFF, AA WRIGHT, LL LEMONS, JA WRIGHT, E SHANKARAN, S TYSON, JE KORONES, SB BAUER, CR STOLL, BJ PAPILE, LA DONOVAN, EF EHRENKRANZ, RA AF VREMAN, HJ STEVENSON, DK OH, W FANAROFF, AA WRIGHT, LL LEMONS, JA WRIGHT, E SHANKARAN, S TYSON, JE KORONES, SB BAUER, CR STOLL, BJ PAPILE, LA DONOVAN, EF EHRENKRANZ, RA TI SEMIPORTABLE ELECTROCHEMICAL INSTRUMENT FOR DETERMINING CARBON-MONOXIDE IN BREATH SO CLINICAL CHEMISTRY LA English DT Article DE END-TIDAL BREATH ANALYSIS; GAS CHROMATOGRAPHY COMPARED; HYPERBILIRUBINEMIA; JAUNDICE; NEONATES ID ORAL VITAMIN-E; CARBOXYHEMOGLOBIN CONCENTRATION; BILIRUBIN PRODUCTION; PRETERM INFANTS; EXCRETION; JAUNDICE; HYDROGEN; BLOOD; TESTS; TERM AB Measurements of carbon monoxide (CO) in breath can be used for the diagnosis of hemolytic disease. A small, semiportable, easy-to-operate CO instrument was developed at Stanford University and tested at 12 Neonatal Research Network Centers of the National Institute of Child Health and Human Development. A syringe pump delivers 7.7 mL of sample per minute through an activated carbon filter to an electrochemical (EC) sensor having a sensitivity of 0.10 +/- 0.01 V per 1 mu L/L CO in air. The electronically processed sensor signal is displayed on a digital multimeter. For a typical end-tidal CO measurement, corrected for inhaled CO, three 10- to 12-mL breath and room air samples are manually or mechanically collected and analyzed. CO determination in breath samples from 108 healthy, 1-day-old infants of nonsmoking mothers compared favorably with determinations by gas chromatography (GC), 1.3 +/- 0.8 vs 1.2 +/- 0.8 (mean +/- SD), respectively, with a regression equation of EC = 0.95 GC + 0.13 (r(2) = 0.98). The results demonstrate that the EC-CO instrument yields results that are comparable with those obtained by the more difficult to perform GC assay. C1 BROWN UNIV,PROVIDENCE,RI 02912. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NICHHD,BETHESDA,MD 20892. INDIANA UNIV,INDIANAPOLIS,IN 46204. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC. WAYNE STATE UNIV,DETROIT,MI. UNIV TEXAS,SW MED CTR,DALLAS,TX. UNIV TENNESSEE,MEMPHIS,TN. UNIV MIAMI,MIAMI,FL 33152. EMORY UNIV,ATLANTA,GA 30322. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. UNIV CINCINNATI,CINCINNATI,OH. YALE UNIV,NEW HAVEN,CT. RP VREMAN, HJ (reprint author), STANFORD UNIV,SCH MED,DEPT PEDIAT,STANFORD,CA 94305, USA. FU NICHD NIH HHS [U10 HD21364, U10 HD27904, U10 HD27880] NR 22 TC 51 Z9 51 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 1994 VL 40 IS 10 BP 1927 EP 1933 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PL016 UT WOS:A1994PL01600013 PM 7923774 ER PT J AU STEVENSON, DK VREMAN, HJ OH, W FANAROFF, AA WRIGHT, LL LEMONS, JA VERTER, J SHANKARAN, S TYSON, JE KORONES, SB BAUER, CR STOLL, BJ PAPILE, LA OKAH, F EHRENKRANZ, RA AF STEVENSON, DK VREMAN, HJ OH, W FANAROFF, AA WRIGHT, LL LEMONS, JA VERTER, J SHANKARAN, S TYSON, JE KORONES, SB BAUER, CR STOLL, BJ PAPILE, LA OKAH, F EHRENKRANZ, RA TI BILIRUBIN PRODUCTION IN HEALTHY TERM INFANTS AS MEASURED BY CARBON-MONOXIDE IN BREATH SO CLINICAL CHEMISTRY LA English DT Article DE END-TIDAL BREATH ANALYSIS; HYPERBILIRUBINEMIA; JAUNDICE; NEONATES; HEMOLYSIS; DIABETES ID PULMONARY EXCRETION; DIABETIC MOTHERS; INDEX; TURNOVER; JAUNDICE; HYDROGEN; BLOOD AB To describe total bilirubin production in healthy term infants, we measured the end-tidal breath CO, corrected for ambient CO (ETCOc), with an automated sampler and electrochemical (EC) CO instrument. For infants of mothers with a negative Coombs' test, the ETCOc was 1.3 +/- 0.7 mu L/L (n = 397) and the serum bilirubin on day 3 postpartum was 73 +/- 35 mg/L (n = 381). In contrast, the ETCOc for infants with ABO or Rh incompatibility, a positive direct Coombs' test, and bilirubin >130 mg/L (n = 9) was significantly higher, 1.8 +/- 0.8 mu L/L, than for those who had a positive Coombs' test result but whose bilirubin was less than or equal to 130 mg/L (n = 12), 1.0 +/- 0.5 mu L/L (P <0.05). At 2 to 8 h postpartum seven term babies from mothers with insulin-dependent diabetes had ETCOc of 1.8 +/- 0.7 mu L/L, significantly higher than that in the other term infants [1.3 F 0.7 mu L/L (n = 390), P <0.04]. Their bilirubin concentration at 72 +/- 12 h was also higher: 121 +/- 45 mg/L (n = 7) vs 73 +/- 34 mg/L (n = 374; P = 0.03). We conclude that ETCOc measurements may be helpful in understanding the mechanisms of jaundice in healthy term infants in a variety of conditions. C1 BROWN UNIV,PROVIDENCE,RI 02912. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NICHHD,BETHESDA,MD 20892. INDIANA UNIV,INDIANAPOLIS,IN 46204. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC. WAYNE STATE UNIV,DETROIT,MI. UNIV TEXAS,SW MED CTR,DALLAS,TX. UNIV TENNESSEE,MEMPHIS,TN. UNIV MIAMI,MIAMI,FL 33152. EMORY UNIV,ATLANTA,GA 30322. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. UNIV CINCINNATI,CINCINNATI,OH. YALE UNIV,NEW HAVEN,CT. RP STEVENSON, DK (reprint author), STANFORD UNIV,SCH MED,DEPT PEDIAT,STANFORD,CA 94305, USA. FU NICHD NIH HHS [U10 HD27904, U10 HD27880, U10 HD21364] NR 25 TC 44 Z9 44 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 1994 VL 40 IS 10 BP 1934 EP 1939 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PL016 UT WOS:A1994PL01600014 PM 7923775 ER PT J AU SAMPSON, M RUDDEL, M ZWEIG, M ELIN, RJ AF SAMPSON, M RUDDEL, M ZWEIG, M ELIN, RJ TI FALSELY HIGH-CONCENTRATION OF SERUM LUTROPIN MEASURED WITH THE ABBOTT IMX SO CLINICAL CHEMISTRY LA English DT Letter ID THYROXINE RP SAMPSON, M (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BETHESDA,MD 20892, USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 1994 VL 40 IS 10 BP 1976 EP 1977 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PL016 UT WOS:A1994PL01600025 PM 7923783 ER PT J AU LEKSTROMHIMES, JA HOLLAND, SM DECARLO, ES MILLER, J LEITMAN, SF CHANG, R BAKER, AR GALLIN, JI AF LEKSTROMHIMES, JA HOLLAND, SM DECARLO, ES MILLER, J LEITMAN, SF CHANG, R BAKER, AR GALLIN, JI TI TREATMENT WITH INTRALESIONAL GRANULOCYTE INSTILLATIONS AND INTERFERON-GAMMA FOR A PATIENT WITH CHRONIC GRANULOMATOUS-DISEASE AND MULTIPLE HEPATIC-ABSCESSES SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID TRANSFUSION THERAPY; HUMAN-NEUTROPHILS; INFECTION; CHILDHOOD AB We present the case of a 16-year-old girl with p22(phox)-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon-gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NCI,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. RP LEKSTROMHIMES, JA (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N228,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 18 Z9 18 U1 0 U2 1 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 OCT PY 1994 VL 19 IS 4 BP 770 EP 773 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PK857 UT WOS:A1994PK85700023 PM 7803648 ER PT J AU BORRADORI, L CALDWELL, JB BRIGGAMAN, RA JAMES, WD YANCEY, KB AF BORRADORI, L CALDWELL, JB BRIGGAMAN, RA JAMES, WD YANCEY, KB TI PASSIVE TRANSFER OF AUTOANTIBODIES FROM A PATIENT WITH MUTILATING EPIDERMOLYSIS-BULLOSA ACQUISITA (EBA) INDUCES SPECIFIC ALTERATIONS IN ME SKIN OF NEONATAL MICE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIH,DERMATOL BRANCH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DERMATOL SERV,WASHINGTON,DC 20307. UNIV N CAROLINA,DEPT DERMATOL,CHAPEL HILL,NC 27514. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A454 EP A454 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500557 ER PT J AU LAZAROVA, Z YANCEY, KB AF LAZAROVA, Z YANCEY, KB TI THE REACTIVITY OF AUTOANTIBODIES FROM PATIENTS WITH DEFINED SUBEPIDERMAL BULLOUS DISEASES AGAINST 1M NACL SPLIT SKIN (SSS) - SPECIFICITY, SENSITIVITY, AND PRACTICAL CONSIDERATIONS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NIH,DERMATOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A463 EP A463 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500599 ER PT J AU MELNICK, L PARSHAD, R SANFORD, KK PRICE, FM NEE, LE TARONE, RE ROBBINS, JH AF MELNICK, L PARSHAD, R SANFORD, KK PRICE, FM NEE, LE TARONE, RE ROBBINS, JH TI DEFECTIVE-DNA REPAIR IN ALZHEIMER-DISEASE - USE IN A PREDICTIVE TEST ON CULTURED-CELL LINES SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD. NINCDS,BETHESDA,MD. HOWARD UNIV,COLL MED,WASHINGTON,DC. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A464 EP A464 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500604 ER PT J AU PANOS, RJ BAK, P RUBIN, JS AF PANOS, RJ BAK, P RUBIN, JS TI INTRATRACHEAL INSTILLATION OF KERATINOCYTE GROWTH-FACTOR PREVENTS HYPEROXIA-INDUCED MORTALITY IN RATS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,DEPT MED,DIV PULM,CHICAGO,IL 60611. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A426 EP A426 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500436 ER PT J AU WINOKUR, PL SARAFI, TR MCBRIDE, AA AF WINOKUR, PL SARAFI, TR MCBRIDE, AA TI ANALYSIS OF THE BOVINE PAPILLOMAVIRUS E2 PROTEIN AND ITS ROLE IN VIRAL REPLICATION SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV IOWA,DEPT MED,IOWA CITY,IA 52242. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A379 EP A379 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500187 ER PT J AU SEIFERT, WE GOTTE, SW LETO, TL WELDON, PJ AF SEIFERT, WE GOTTE, SW LETO, TL WELDON, PJ TI LIPIDS AND PROTEINS IN THE RATHKES GLAND SECRETIONS OF THE NORTH-AMERICAN MUD TURTLE (KINOSTERNON SUBRUBRUM) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE LIPIDS; PROTEINS; RATHKES GLAND SECRETIONS; KINOSTERNON SUBRUBRUM ID SEA-TURTLES; LEPIDOCHELYS-KEMPI; CARETTA-CARETTA AB Lipids and proteins in the Rathke's gland secretions of the North American mud turtle (Kinosternon subrubrum, Kinosternidae) were analyzed by gas chromatography-mass spectrometry (GC-MS) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Analysis by GC-MS indicates 2,3-dihydroxypropanal and C-3-C-24 free or esterified fatty acids. Analysis by SDS-PAGE indicates a major protein component with an approximate molecular mass of 60 kDa and minor components ranging from ca. 23 to 34 kDa. The major component of K. subrubrum glandular secretions exhibits a mobility that matches that of the Kemp's ridley sea turtle (Lepidochelys kempi, Cheloniidae), suggesting that these proteins are evolutionarily conserved. C1 NATL MUSEUM NAT HIST,NATL BIOL SURVEY,BIOL SURVEY PROJECT,WASHINGTON,DC 20560. NIAID,HOST DEF LAB,BETHESDA,MD 20892. TEXAS A&M UNIV,DEPT BIOL,COLLEGE STN,TX 77843. RP SEIFERT, WE (reprint author), UNIV TEXAS,SCH MED,CTR ANALYT CHEM,POB 20708,HOUSTON,TX 77225, USA. NR 9 TC 5 Z9 5 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol B-Biochem. Molec. Biol. PD OCT-NOV PY 1994 VL 109 IS 2-3 BP 459 EP 463 DI 10.1016/0305-0491(94)90029-9 PG 5 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA PZ171 UT WOS:A1994PZ17100029 PM 7553355 ER PT J AU HENKART, PA SITKOVSKY, MV AF HENKART, PA SITKOVSKY, MV TI CYTOTOXIC LYMPHOCYTES - 2 WAYS TO KILL TARGET-CELLS SO CURRENT BIOLOGY LA English DT Note ID LYSIS AB Of the two pathways implicated in target-cell damage by cytotoxic lymphocytes, secretory granule exocytosis seems to dominate in anti-viral immunity whereas the Fas pathway may regulate immune responses. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20814. RP HENKART, PA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20814, USA. NR 13 TC 31 Z9 31 U1 1 U2 5 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 OCT 1 PY 1994 VL 4 IS 10 BP 923 EP 925 DI 10.1016/S0960-9822(00)00207-4 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PN161 UT WOS:A1994PN16100013 PM 7531594 ER PT J AU PARDHASARADHI, K KUTTY, RK PARK, CS KRISHNA, G AF PARDHASARADHI, K KUTTY, RK PARK, CS KRISHNA, G TI CLONING AND SEQUENCING OF HEAT-SHOCK FACTOR (HSF1) CDNA FROM HUMAN RETINA SO CURRENT EYE RESEARCH LA English DT Article DE HEAT SHOCK FACTOR 1; NORTHERN BLOT ANALYSIS; CDNA CLONING; HUMAN RETINA; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION ID TRANSCRIPTION FACTOR; MOLECULAR-CLONING; BINDING; EXPRESSION; PROTEIN; ACTIVATION; GENES AB Transcription of heat shock genes takes place in response to the exposure of cells to elevated temperatures or other stress conditions. Heat shock transcription factor (HSF) plays an important role in the activation of such transcription. We report here the identification of human heat shock factor from human retina by RT-PCR and cloning studies. Human retinal poly A(+) RNA was reverse transcribed and the cDNAs thus obtained were subjected to PCR using a set of primers designed from the reported cDNA sequence for human HSF1. The amplified product showed 100% sequence identity with the appropriate region of HSF1. A human retinal cDNA library was screened to isolate the full length cDNA for heat shock factor, which showed 100% sequence identity to that reported for human HSF1. Northern blot analysis showed the size of human retinal HSF to be similar to 2.4 kb. C1 NHLBI,CHEM PHARMACOL LAB,DRUG TISSUE INTERACT SECT,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 24 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 1994 VL 13 IS 10 BP 739 EP 742 DI 10.3109/02713689409047008 PG 4 WC Ophthalmology SC Ophthalmology GA PL804 UT WOS:A1994PL80400005 PM 7842723 ER PT J AU KOCH, PJ FRANKE, WW AF KOCH, PJ FRANKE, WW TI DESMOSOMAL CADHERINS - ANOTHER GROWING MULTIGENE FAMILY OF ADHESION MOLECULES SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; CELL-ADHESION; PEMPHIGUS-VULGARIS; BETA-CATENIN; CYTOPLASMIC DOMAINS; HUMAN DESMOGLEIN; DESMOPLAKIN-II; MESSENGER-RNAS; PLAKOGLOBIN; IDENTIFICATION AB The formation of supracellular structures, i.e. tissues and organs, is dependent on the spatially and temporally regulated formation of semistable cell-cell contacts. In recent years, the molecular components of such cell junctions, especially those occurring in epithelial cells, have been studied extensively, and the main proteins and glycoproteins of the 'adhering junctions' such as the desmosomes and the zonula adherens of polar epithelial cells have been characterized. We are now beginning to understand the complex protein-protein interactions that contribute to the assembly and disassembly of these structures and their roles in the attachment of specific filaments of the cytoskeleton. C1 GERMAN CANC RES CTR,DIV CELL BIOL,D-69120 HEIDELBERG,GERMANY. RP KOCH, PJ (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 44 TC 171 Z9 171 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1994 VL 6 IS 5 BP 682 EP 687 DI 10.1016/0955-0674(94)90094-9 PG 6 WC Cell Biology SC Cell Biology GA PH465 UT WOS:A1994PH46500006 PM 7833048 ER PT J AU FAST, PE MATHIESON, BJ SCHULTZ, AM AF FAST, PE MATHIESON, BJ SCHULTZ, AM TI EFFICACY TRIALS OF AIDS VACCINES - HOW SCIENCE CAN INFORM ETHICS - GUEST EDITORIAL SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS VACCINE; LYMPHOCYTE PROLIFERATIVE RESPONSES; GP160 RECOMBINANT VACCINIA; EXPRESSING HIV ENVELOPE; MONOCLONAL-ANTIBODY; NAIVE ADULTS; IMMUNIZATION; CHIMPANZEES; INFECTION; SAFETY RP FAST, PE (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 70 TC 8 Z9 8 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 OCT PY 1994 VL 6 IS 5 BP 691 EP 697 DI 10.1016/0952-7915(94)90070-1 PG 7 WC Immunology SC Immunology GA PM735 UT WOS:A1994PM73500001 PM 7826523 ER PT J AU TOPALIAN, SL AF TOPALIAN, SL TI MHC CLASS-II RESTRICTED TUMOR-ANTIGENS AND THE ROLE OF CD4(+) T-CELLS IN CANCER-IMMUNOTHERAPY SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; INFILTRATING LYMPHOCYTES; AUTOLOGOUS TUMOR; CYTOKINE SECRETION; MURINE LEUKEMIA; RECOGNITION; INTERLEUKIN-2; GENERATION; CARCINOMAS AB Recent studies in human and murine systems suggest a central role for CD4(+) T cells in initiating, effecting and maintaining anti-tumor immunity. Characterization of the tumor-associated antigens recognized by CD4(+) T cells may prove critical to the success of cancer immunotherapy strategies. RP TOPALIAN, SL (reprint author), NCI,BLDG 10,ROOM 2B47,BETHESDA,MD 20892, USA. NR 32 TC 96 Z9 97 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1994 VL 6 IS 5 BP 741 EP 745 DI 10.1016/0952-7915(94)90078-7 PG 5 WC Immunology SC Immunology GA PM735 UT WOS:A1994PM73500009 PM 7826529 ER PT J AU OTTESEN, EA AF OTTESEN, EA TI THE HUMAN FILARIASES - NEW UNDERSTANDINGS, NEW THERAPEUTIC STRATEGIES SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Article AB The discovery of techniques to localize and recover Wuchereria bancrofti parasites from patients and the use of molecular toots to probe the genomes of all the filariae have permitted unprecedented advances in understanding the biology of these parasites. Recognition that the immune responses of most infected patients are 'contrainflammatory' suggests that their primary role is to contain or limit inflammation around the parasite, not promote it. Pathology appears to develop either in response to parasite products or when the host is unable to contain local inflammation- around dying microfilariae in the skin of onchocerciasis patients or in response to bacterial or fungal super-infection of tissues with compromised lymphatic function in patients with lymphatic filariasis. Therapeutic strategies to control morbidity associated with these infections are focused on decreasing both the parasite burden and the inflammatory burden caused by super-infecting microorganisms. Effective treatment of affected populations is now possible with single annual doses of ivermectin (onchocerciasis) or diethylcarbamazine with or without ivermectin (lymphatic filariasis). RP OTTESEN, EA (reprint author), NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 0 TC 43 Z9 44 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 1994 VL 7 IS 5 BP 550 EP 558 DI 10.1097/00001432-199410000-00006 PG 9 WC Infectious Diseases SC Infectious Diseases GA PN232 UT WOS:A1994PN23200006 ER PT J AU BAX, A AF BAX, A TI MULTIDIMENSIONAL NUCLEAR-MAGNETIC-RESONANCE METHODS FOR PROTEIN STUDIES SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID ISOTOPICALLY-ENRICHED PROTEINS; HETERONUCLEAR CROSS-POLARIZATION; PULSED-FIELD GRADIENTS; CORRELATING BACKBONE AMIDE; SIDE-CHAIN RESONANCES; COUPLING-CONSTANTS; C-13/N-15-ENRICHED PROTEINS; SENSITIVITY IMPROVEMENT; SEQUENTIAL ASSIGNMENT; C-13-LABELED PROTEINS AB Nuclear magnetic resonance (NMR) technology has advanced significantly over the past few years. After the initial development of three- and four-dimensional NMR spectroscopy, several important improvements on these experiments have been made; these offer significantly higher sensitivity and improved resolution, resulting in additional structural constraints. Other methodological improvements now make it possible to obtain complete resonance assignments, even in partially denatured proteins, opening new windows for studying the protein folding problem. RP BAX, A (reprint author), NIH,BETHESDA,MD 20892, USA. NR 49 TC 168 Z9 173 U1 1 U2 9 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 OCT PY 1994 VL 4 IS 5 BP 738 EP 744 DI 10.1016/S0959-440X(94)90173-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PQ002 UT WOS:A1994PQ00200010 ER PT J AU RICHARDSON, DL LOOMIS, WF KIMMEL, AR AF RICHARDSON, DL LOOMIS, WF KIMMEL, AR TI PROGRESSION OF AN INDUCTIVE SIGNAL ACTIVATES SPORULATION IN DICTYOSTELIUM-DISCOIDEUM SO DEVELOPMENT LA English DT Article DE GENE EXPRESSION; SPIA; 8-BR-CAMP; PROTEIN KINASE A; CULMINATION; EXPRESSION GRADIENT ID DEPENDENT PROTEIN-KINASE; POLARITY GENE HEDGEHOG; CAMP RECEPTOR GENE; CELL-DIFFERENTIATION; EMBRYONIC INDUCTION; EXTRACELLULAR CAMP; STALK CELL; EXPRESSION; PRESPORE; SPORE AB spiA, a marker for sporulation, is expressed during the culmination stage of Dictyostelium development, when the mass of prespore cells has moved partly up the newly formed stalk. Strains containing a full-length spiA promoter/lacZ fusion were stained for beta-galactosidase activity at intervals during development. The results indicate that expression of spiA initiates in prespore cells at the prestalk/prespore boundary (near the apex) and extends downward into the prespore mass as culmination continues. A spatial gradient of staining expands from the top of the prespore mass and intensifies until the front of activation reaches the bottom, whereupon the entire region stains darkly. The spiA promoter can be deleted to within 301 bp of the transcriptional start site with no effect on the relative strength, timing or spatial localization of expression. Further 5' deletions from -301 to -175 reduce promoter strength incrementally, although timing and spatial expression are not affected. Deletions to -159 and beyond result in inactive promoters. Treatment of early developmental structures with 8-Br-cAMP in situ activates the intracellular cAMP-dependent protein kinase (PKA) and precociously induces spiA expression and sporulation. The absence of an apparent gradient of staining in these structures suggests that PKA is equivalently activatable throughout the prespore region and that all prespore cells are competent to express spiA. Thus, we postulate that the pattern of expression of spiA reveals the progression of an inductive signal for sporulation and suggest that this signal may originate from the prestalk cells at the apex. C1 NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. FU NIGMS NIH HHS [GM23822] NR 56 TC 73 Z9 74 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 1994 VL 120 IS 10 BP 2891 EP 2900 PG 10 WC Developmental Biology SC Developmental Biology GA PN076 UT WOS:A1994PN07600014 PM 7607079 ER PT J AU ALMOUZNI, G KHOCHBIN, S DIMITROV, S WOLFFE, AP AF ALMOUZNI, G KHOCHBIN, S DIMITROV, S WOLFFE, AP TI HISTONE ACETYLATION INFLUENCES BOTH GENE-EXPRESSION AND DEVELOPMENT OF XENOPUS-LAEVIS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID SODIUM-BUTYRATE; TRICHOSTATIN-A; TRANSCRIPTION; CHROMATIN; DNA; OOCYTES; CELLS; DIFFERENTIATION; ACTIVATION; NUCLEOSOME AB We examine the potential role of histone hyperacetylation in gene activation during Xenopus development using Trichostatin A, (TSA), a specific inhibitor of histone deacetylase. We find that TSA is very effective in inducing both core histone hyperacetylation and histone H1 degrees gene expression in a Xenopus somatic cell line. In contrast, TSA does not induce histone hyperacetylation or histone H1 degrees transcription in Xenopus oocytes. Histone hyperacetylation is developmentally regulated during Xenopus embryogenesis; hyperacetylated histones first accumulate early in gastrulation. The capacity of TSA to induce histone H1 degrees gene expression correlates with the induction of histone hyperacetylation. Concentrations of TSA sufficient to induce histone hyperacetylation in Xenopus embryos delay gastrulation and cause diminished midtrunk and posterior formation, suggesting defects in mesoderm formation. Although the constitutive hyperacetylation of the histones does not prevent either the cell division or differentiation sufficient for early morphogenesis it has a role in establishing stable states of differential gene activity during gastrulation. (C) 1994 Academic Press, Inc. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI dimitrov, stefan/M-7697-2013; Khochbin, Saadi/M-8090-2013 NR 65 TC 107 Z9 111 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT PY 1994 VL 165 IS 2 BP 654 EP 669 DI 10.1006/dbio.1994.1283 PG 16 WC Developmental Biology SC Developmental Biology GA PP811 UT WOS:A1994PP81100028 PM 7958429 ER PT J AU COWIE, CC HARRIS, MI EBERHARDT, MS AF COWIE, CC HARRIS, MI EBERHARDT, MS TI FREQUENCY AND DETERMINANTS OF SCREENING FOR DIABETES IN THE US SO DIABETES CARE LA English DT Article ID UNITED-STATES POPULATION; BLOOD-GLUCOSE; NIDDM; PREVALENCE; DISEASE; HEALTH; YR AB OBJECTIVE- To determine the prevalence of risk factors for non-insulin-dependent diabetes mellitus (NIDDM) and the frequency of screening for NIDDM in U.S. adults. RESEARCH DESIGN AND METHODS- A detailed questionnaire was administered to a representative sample of 19,680 adults greater than or equal to 18 years of age who reported no medical history of diabetes in the 1989 National Health Interview Survey (NHIS). Information was obtained on risk factors for diabetes, complications related to diabetes, and whether the subjects had been screened for diabetes in the past year. Women reporting pregnancy in the past year were excluded from analysis. The prevalence of undiagnosed NIDDM according to the frequency of risk factors for NIDDM was determined based on oral glucose tolerance data from the National Health and Nutrition Examination Survey (NHANES) II and Hispanic Health and Nutrition Examination Survey (HHANES). RESULTS- Prevalence of undiagnosed NIDDM based on the NHANES II and HHANES increased with age, obesity, and family history of diabetes, reaching 11.7 % in people with all three risk factors. Based on the NHIS, 77.5% of U.S. adults with no medical history of diabetes (131 million people) had at least one risk factor for NIDDM or complication related to NIDDM, and 22.9% (38 million people) had three or more risk factors or complications. Approximately 31% of adults reported being screened for diabetes in the past year. Screening rates increased with an increasing number of risk factors, but even among those with three risk factors, only 38.6% were screened for NIDDM. CONCLUSIONS- More than 7 million U.S. adults have undiagnosed NIDDM. Nevertheless, screening for diabetes in high-risk groups occurs substantially less frequently than necessary to detect undiagnosed NIDDM and institute appropriate hypoglycemic treatment. C1 NIDDKD,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP COWIE, CC (reprint author), SOCIAL & SCI SYST INC,7101 WISCONSIN AVE,STE 1300,BETHESDA,MD 20814, USA. NR 24 TC 29 Z9 31 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1994 VL 17 IS 10 BP 1158 EP 1163 DI 10.2337/diacare.17.10.1158 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ311 UT WOS:A1994PJ31100010 PM 7821136 ER PT J AU KOVAL, A KULIK, V DUGUAY, S PLISETSKAYA, E ADAMO, ML ROBERTS, CT LEROITH, D KAVSAN, V AF KOVAL, A KULIK, V DUGUAY, S PLISETSKAYA, E ADAMO, ML ROBERTS, CT LEROITH, D KAVSAN, V TI CHARACTERIZATION OF A SALMON INSULIN-LIKE GROWTH-FACTOR-I PROMOTER SO DNA AND CELL BIOLOGY LA English DT Article ID MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; IGF-I; GENE; EXPRESSION; SITES; ORGANIZATION; CDNAS AB We have identified four transcription initiation sites in the salmon insulin-like growth factor I (IGF-I) gene. Use of the most upstream transcription start site generates a minor mRNA species with a 5' untranslated region (UTR) of approximately 450-550 nucleotides, whereas transcription starting at the downstream initiation sites results in more abundant IGF-I mRNAs with 5'-UTRs approximately 250,245, and 165 nucleotides in length. No consensus TATA box-like elements are present immediately upstream of the most upstream start site identified, nor is this region particularly GC-rich. Transient expression assays, however, demonstrated orientation-dependent promoter activity in a 386-nucleotide-long fragment containing the major downstream transcription start sites. Additionally, reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated tissue and developmental stage-specific use of the various transcription start sites identified. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,DEPT BIOSYNTHESIS NUCLEIC ACIDS,KIEV 252627,UKRAINE. UNIV WASHINGTON,SCH FISHERIES,SEATTLE,WA 98195. OI Roberts, Charles/0000-0003-1756-5772 NR 26 TC 12 Z9 12 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1994 VL 13 IS 10 BP 1057 EP 1062 DI 10.1089/dna.1994.13.1057 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA PP859 UT WOS:A1994PP85900008 PM 7945938 ER PT J AU CHESKIN, LJ FUDALA, PJ JOHNSON, RE AF CHESKIN, LJ FUDALA, PJ JOHNSON, RE TI A CONTROLLED COMPARISON OF BUPRENORPHINE AND CLONIDINE FOR ACUTE DETOXIFICATION FROM OPIOIDS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE OPIOID; DETOXIFICATION; BUPRENORPHINE; CLONIDINE; CONTROLLED TRIAL ID OPIATE-WITHDRAWAL SYMPTOMS; HEROIN-ADDICTS; RAPID DETOXIFICATION; ABRUPT WITHDRAWAL; METHADONE; DEPENDENCE; MAINTENANCE; GUANFACINE; EFFICACY; NALOXONE AB We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms. C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21224. NR 61 TC 73 Z9 78 U1 2 U2 4 PU ELSEVIER SCI 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 OCT PY 1994 VL 36 IS 2 BP 115 EP 121 DI 10.1016/0376-8716(94)90093-0 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA PL315 UT WOS:A1994PL31500006 PM 7851278 ER PT J AU SCHUTZ, CG RAPITI, E VLAHOV, D ANTHONY, JC AF SCHUTZ, CG RAPITI, E VLAHOV, D ANTHONY, JC TI SUSPECTED DETERMINANTS OF ENROLLMENT INTO DETOXIFICATION AND METHADONE-MAINTENANCE TREATMENT AMONG INJECTING DRUG-USERS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE TREATMENT ENTRY; INJECTING DRUG USE; SUBSTANCE ABUSE; HUMAN IMMUNODEFICIENCY VIRUS; ACQUIRED IMMUNODEFICIENCY SYNDROME ID SEEKING; ADDICTS AB Our primary aim in this study has been to evaluate selected conditions thought to influence the entry of injecting drug users (IDU) into detoxification and methadone maintenance programs, making use of a prospective study design to strengthen a cross-sectional investigation of these conditions. To begin our investigation, we analyzed cross-sectionally gathered data on 2879 IDUs who had been recruited through extensive community outreach efforts and who were interviewed at the time of recruitment. We then tested our hypotheses about suspected determinants of entry into treatment by analyzing prospectively gathered data on 1039 active drug users who had no recent history of being treated for drug problems. Among these 1039 IDUs (a subset of the initial cross-sectional sample), 144 entered a detoxification program between their recruitment interview and their next follow-up interview, conducted about six months after recruitment (range: 3.5-9.5 months) and 64 entered a methadone maintenance program during that observation interval. Using multiple logistic regression analyses, we found that a recent drug overdose, relatively higher frequency of injecting drugs, and a history of prior arrest or treatment were independent predictors of entry into detoxification. Being married or living with a partner, being female, a lengthy duration of drug use (> 10 years), and a history of prior treatment were independent predictors of entry into methadone maintenance. These findings shed light on what appears to be a different profile of suspected determinants of entry into a detoxification treatment versus methadone maintenance treatment, and help to clarify some potential differences between treated and untreated drug users that ought to be considered when evaluating results of investigations with IDU participants recruited solely from treatment settings. C1 LATIUM REG HLTH AUTHOR,EPIDEMIOL UNIT,ROME,ITALY. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD. RP SCHUTZ, CG (reprint author), NIDA,INTRAMURAL RES PROGRAM,ETIOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA 04334, DA 05911] NR 15 TC 56 Z9 57 U1 1 U2 2 PU ELSEVIER SCI 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 OCT PY 1994 VL 36 IS 2 BP 129 EP 138 DI 10.1016/0376-8716(94)90095-7 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA PL315 UT WOS:A1994PL31500008 PM 7851280 ER PT J AU SUSLA, GM DEW, RB AF SUSLA, GM DEW, RB TI ANTIENDOTOXIN MONOCLONAL-ANTIBODIES - WHAT FUTURE NOW SO DRUG SAFETY LA English DT Article RP SUSLA, GM (reprint author), NIH,CTR CLIN,DEPT PHARM,BLDG 10,ROOM 1N-257,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD OCT PY 1994 VL 11 IS 4 BP 215 EP 222 DI 10.2165/00002018-199411040-00001 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA PL658 UT WOS:A1994PL65800001 PM 7848542 ER PT J AU THOMAS, DW BOYD, MR CARDELLINA, JH GEREAU, RE JATO, J SYMONDS, P AF THOMAS, DW BOYD, MR CARDELLINA, JH GEREAU, RE JATO, J SYMONDS, P TI SUSTAINABLE HARVEST OF ANCISTROCLADUS-KORUPENSIS (ANCISTROCLADACEAE) LEAF-LITTER FOR RESEARCH ON HIV SO ECONOMIC BOTANY LA English DT Note C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. MISSOURI BOT GARDEN,ST LOUIS,MO 63166. UNIV YAOUNDE,CTR HLTH SCI,YAOUNDE,CAMEROON. WORLD WIDE FUND NAT,GODALMING GU7 IRK,SURREY,ENGLAND. RP THOMAS, DW (reprint author), OREGON STATE UNIV,OFF INT RES & DEV,CORVALLIS,OR 97331, USA. NR 3 TC 4 Z9 6 U1 0 U2 0 PU NEW YORK BOTANICAL GARDEN PI BRONX PA PUBLICATIONS DEPT, BRONX, NY 10458 SN 0013-0001 J9 ECON BOT JI Econ. Bot. PD OCT-DEC PY 1994 VL 48 IS 4 BP 413 EP 414 DI 10.1007/BF02862237 PG 2 WC Plant Sciences SC Plant Sciences GA PU892 UT WOS:A1994PU89200005 ER PT J AU TORO, C DEUSCHL, G THATCHER, R SATO, S KUFTA, C HALLETT, M AF TORO, C DEUSCHL, G THATCHER, R SATO, S KUFTA, C HALLETT, M TI EVENT-RELATED DESYNCHRONIZATION AND MOVEMENT-RELATED CORTICAL POTENTIALS ON THE ECOG AND EEG SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MOTOR CORTEX; ELECTROPHYSIOLOGY; ELECTROENCEPHALOGRAPHY ID VOLUNTARY MOVEMENTS; FINGER MOVEMENTS; VISUAL-CORTEX; SCALP; TOPOGRAPHY; SYNCHRONIZATION; OSCILLATIONS; FIELDS; CAT AB Event-related desynchronization (ERD) 2.0 sec before and 1.0 sec after movement in the frequency bands of 8-10, 10-12, 12-20 and 20-30 Hz and movement-related cortical potentials (MRCPs) to self-paced movements were studied from subdural recordings over the central region in 3 patients, and from scalp-recorded EEGs in 20 normal volunteers. In direct cortical recordings, the peak ERD response and peak MRCP amplitude to self-paced finger movements were maximal over recording sites in the contralateral hand motor representations. The topography and time of onset of the ERD response to finger and foot movements suggest that the ERD responses in the 8-10 Hz and 10-12 Hz bands are more somatotopically restricted than the responses in the higher frequency hands. The power recovery and subsequent overshoot in the different frequency bands occurred in an orderly fashion with the faster frequencies recovering earlier. The ERD responses on the scalp-recorded EEGs were of lower magnitude and more widely distributed than those occurring on the subdural recordings. Across the population, there was no relation between the magnitude of the ERD response in any of the frequency bands studied and the peak amplitude of the negative slope (pNS') and the frontal peak of the motor potential (fpMP) of the MRCPs. MRCPs and ERD responses originate in similar cortical regions and share some common timing features, but the magnitude and spatial distribution of the two responses appear to be independent of each other, which suggests that the physiological mechanisms governing these two events are different and may represent different aspects of motor cortex activation. Differences in the timing and topographical features of the ERD responses in the various frequency bands also suggest a distinct functional significance for the various spectral components of the electrical activity in the motor cortex. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NINCDS,EEG LAB,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RI Deuschl, Gunther/A-7986-2010 NR 41 TC 203 Z9 208 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1994 VL 93 IS 5 BP 380 EP 389 DI 10.1016/0168-5597(94)90126-0 PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA PN330 UT WOS:A1994PN33000008 PM 7525246 ER PT J AU CHAN, KC MAJADLY, F MCCLOUD, TG MUSCHIK, GM ISSAQ, HJ SNADER, KM AF CHAN, KC MAJADLY, F MCCLOUD, TG MUSCHIK, GM ISSAQ, HJ SNADER, KM TI MICELLAR ELECTROKINETIC CHROMATOGRAPHY OF THE ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) AGENT MICHELLAMINE-B WITH ABSORPTION AND LASER-INDUCED FLUORESCENCE DETECTION SO ELECTROPHORESIS LA English DT Article ID CAPILLARY ELECTROPHORESIS; SEPARATION AB Micellar electrokinetic chromatography (MEKC) was applied to the separation of the anti-HIV agents, michellamines A and B, and two other structurally related monomers found in the extract of the Ancistrocladus plants. Using buffers containing either 10 mM sodium phosphate (pH 7.0), 50 mM sodium deoxycholate and 10-20% acetonitrile or 5 mM sodium phosphate (pH 7.0), 20 mM sodium dodecyl sulfate and 25% acetonitrile allowed baseline separations of the four components in the mixture in less than 10 min. The MEKC methods gave sharper peaks and better resolution compared to high-performance liquid chromatography. For MEKC separation of the plant extracts, UV absorption detection provided adequate sensitivity; however, higher sensitivity could be achieved with UV laser-induced fluorescence detection (LIF). Using the sodium dodecyl sulfate-containing buffer and LIF, the limit of detection for michellamine B was similar to 2 ng/mL. The sensitivity was degraded similar to 100-fold when using the deoxycholate buffer because of high background fluorescence. Preliminary results show that MEKC with LIF is feasible for the sensitive detection of michellamine B in serum. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,DCT,DTP,NAT PROD BRANCH,FREDERICK,MD. NR 15 TC 8 Z9 8 U1 0 U2 0 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 OCT PY 1994 VL 15 IS 10 BP 1310 EP 1315 DI 10.1002/elps.11501501199 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PQ536 UT WOS:A1994PQ53600014 PM 7895724 ER PT J AU NOLAN, EM HELMAN, LJ BURTON, DW DEFTOS, LJ AF NOLAN, EM HELMAN, LJ BURTON, DW DEFTOS, LJ TI CLONING OF THE HUMAN CHROMOGRANIN-A PROMOTER AND IDENTIFICATION OF A SEQUENCE THAT POSSESSES ENHANCER-LIKE ACTIVITY SO ENDOCRINE LA English DT Article ID HUMAN CALCITONIN GENE; CELL-LINES; TRANSCRIPTION FACTOR; RIBONUCLEIC-ACID; SECRETION; PROTEIN; PEPTIDE; PANCREASTATIN; EXPRESSION; HORMONE AB Chromogranin A (CgA) is widely expressed in endocrine organs and in cells of the diffuse neuroendocrine system, An understanding of the transcriptional mechanisms involved in the expression of human CgA should provide insights into its regulation in neuroendocrine cells. As an initial step in investigating the regulation of human CgA gene expression, we cloned the gene from a human genomic library and evaluated the transcriptional activity of DNA sequences at its 5' end; We identified by primer extension studies a single transcription start site located 205 bases upstream from the start of translation. We studied the transcriptional activity of upstream sequences by transfection of human cell lines with CgA promoter-growth hormone reporter fusion constructs that included 2300 bases of promoter sequence. We demonstrated that the region 726 base pairs upstream of the transcriptional start-site had transcriptional activity comparable to that of the largest, - 2300 base pair clone, Restriction analysis revealed that a region between - 726 and - 455 in the CgA promoter increased expression by approximately fivefold over constructs lacking this element, Constructs made by processive exonuclease digestion from - 726 to - 590 demonstrated no reduction in transcriptional activity, whereas further digestion to - 566 significantly inhibited transcription, The CgA sequence associated with this elevated expression, CTCAGCACTGTGAAAGT, contains a motif similar to both the basic helix-loop-helix (bHLH) consensus binding site (CANNTG) and also the AP-3 consensus core binding site (TGTGGAAAG); the sequences of these two motifs overlap each other in the CgA promoter, Our results demonstrate that the basal transcriptional activity of the CgA gene is significantly elevated by an upstream sequence found between - 590 and - 566 base pairs, and that this sequence appears to be a unique element that is required for a high level of expression in human cells. C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92161. VET ADM MED CTR,LA JOLLA,CA 92161. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 43 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0969-711X J9 ENDOCRINE JI Endocrine PD OCT PY 1994 VL 2 IS 10 BP 891 EP 897 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QV199 UT WOS:A1994QV19900005 ER PT J AU RUI, H LEBRUN, JJ KIRKEN, RA KELLY, PA FARRAR, WL AF RUI, H LEBRUN, JJ KIRKEN, RA KELLY, PA FARRAR, WL TI JAK2 ACTIVATION AND CELL-PROLIFERATION INDUCED BY ANTIBODY-MEDIATED PROLACTIN RECEPTOR DIMERIZATION SO ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE RECEPTOR; TYROSINE KINASE; EXTRACELLULAR DOMAIN; ERYTHROPOIETIN RECEPTOR; MONOCLONAL-ANTIBODIES; IL-2 RECEPTOR; RAT-LIVER; SUPERFAMILY; BINDING; FAMILY AB Cytokines that interact with receptors of the hematopoietin superfamily have recently been reported to stimulate receptor-associated JAK tyrosine kinases, including PRL activation of JAK2. Unlike other tyrosine kinases, none of the JAK kinases has thus far been implicated in oncogenesis, and their involvement in growth signaling has not been established. Using the PRL-dependent pre-T-cell line Nb2, the present study provided a link between bivalent dimerization of a hematopoietin receptor and activation of its associated JAK kinase, and demonstrated a strong positive correlation between the mitogenic potency of a series of bivalent anti-PRL receptor antibodies and the degree of induced tyrosine phosphorylation of JAK2. Antibody bivalency was required for JAK2 phosphorylation. Monovalent anti-PRL receptor Fab fragments alone were inactive, but their activity could be partially restored by cross-linking with bivalent anti-Fab antibodies. Additional evidence for antibody-induced receptor dimerization was provided by a bell-shaped dose-response curve for the most potent receptor agonist, monoclonal antibody T6. This phenomenon is typically seen at pharmacological concentrations of bivalent ligands, when bound ligand molecules fail to adjoin a second receptor due to occupancy. The present study provided functional support for a model of PRL receptor triggering by ligand-induced receptor homodimerization and subsequent activation of the associated tyrosine kinase JAK2. C1 FAC MED NECKER ENFANTS MALAD,INSERM,U344,F-75730 PARIS 15,FRANCE. RP RUI, H (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CYTOKINE MOLEC MECH SECT,NOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. RI Kelly, Paul/A-7951-2008 FU FIC NIH HHS [5FO5-TWO4300-02] NR 47 TC 117 Z9 117 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1994 VL 135 IS 4 BP 1299 EP 1306 DI 10.1210/en.135.4.1299 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK877 UT WOS:A1994PK87700003 PM 7925093 ER PT J AU BARON, J KLEIN, KO COLLI, MJ YANOVSKI, JA NOVOSAD, JA BACHER, JD CUTLER, GB AF BARON, J KLEIN, KO COLLI, MJ YANOVSKI, JA NOVOSAD, JA BACHER, JD CUTLER, GB TI CATCH-UP GROWTH AFTER GLUCOCORTICOID EXCESS - A MECHANISM INTRINSIC TO THE GROWTH-PLATE SO ENDOCRINOLOGY LA English DT Article ID BONE-GROWTH; CARTILAGE; RATS AB In humans and other mammals, the release from growth-inhibiting conditions, such as glucocorticoid excess, leads to supranormal linear growth. The prevailing explanation for this catch-up growth involves a central nervous system mechanism that compares actual body size to an age-appropriate set-point and adjusts growth rate accordingly via a circulating factor. Although such a neuroendocrine ''sizostat'' was hypothesized more than 30 yr ago, its existence has never been confirmed experimentally. Here we show that suppression of growth within a single growth plate by locally administered glucocorticoid is followed by local catch-up growth that is restricted to the affected growth plate. Thus, the catch-up growth cannot be explained by a neuroendocrine mechanism but, rather, must arise from a mechanism intrinsic to the growth plate. To explain this finding, we propose that the normal senescent decline in growth plate function depends not on age per se, but on the cumulative number of stem cell divisions, and that glucocorticoid administration, by suppressing stem cell proliferation, delays senescence, resulting in catch-up growth after the growth-inhibiting agent is removed. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,SURG RADIOL & PHARM SECT,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 20 TC 84 Z9 84 U1 0 U2 6 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1994 VL 135 IS 4 BP 1367 EP 1371 DI 10.1210/en.135.4.1367 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK877 UT WOS:A1994PK87700011 PM 7925098 ER PT J AU MA, YJ DISSEN, GA MERLINO, G COQUELIN, A OJEDA, SR AF MA, YJ DISSEN, GA MERLINO, G COQUELIN, A OJEDA, SR TI OVEREXPRESSION OF A HUMAN TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) TRANSGENE REVEALS A DUAL ANTAGONISTIC ROLE OF TGF-ALPHA IN FEMALE SEXUAL DEVELOPMENT SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELEASING HORMONE; CENTRAL-NERVOUS-SYSTEM; OVARIAN GRANULOSA-CELLS; PITUITARY-ADRENAL AXIS; LUTEINIZING-HORMONE; MESSENGER-RNA; RAT-BRAIN; PRECOCIOUS PUBERTY; CULTURED NEURONS; GENE-EXPRESSION AB The importance of transforming growth factor-alpha (TGF alpha) in female reproductive development was assessed using transgenic mice bearing a human TGF alpha complementary DNA under the control of a mouse metallothionein-1 promoter (MT1-hTGF alpha). Examination of the brain and ovaries 5 h after a single sc injection of zinc chloride, administered to activate the MT1-hTGF alpha transgene, revealed that prominent sites of human TGF alpha messenger RNA expression within these tissues were the hypothalamus and ovarian follicles, respectively. In vitro experiments showed that acute transgene activation increased hypothalamic release of LH-releasing hormone. In contrast, the ovarian steroidal response to gonadotropins, examined in vitro, was markedly attenuated. Chronic activation of transgene expression by daily administration of zinc chloride delayed the time of first estrus (an index of peripubertal estrogen secretion), but shortened the interval between first estrus and the onset of estrous cyclicity (an index of reproductive competence). Accumulation of small antral follicles, accompanied by thecal hypertrophy and enhanced androgen production, preceded the acquisition of ovulatory capacity. These changes were accompanied by reduced serum LH levels, suggesting that the relative inability of small antral follicles to develop further in TGF alpha-overexpressing mice is at least in part due to inappropriate gonadotropin support. Serum LH levels in these animals may be reduced by an augmented androgen negative feedback signal. Nontransgenic mouse ovaries, placed under the control of a transgenic hypothalamus by heterologous grafting, rapidly ovulated and initiated estrous cyclicity. In contrast, acquisition of reproductive capacity was severely delayed in nontransgenic mice bearing transgenic ovarian grafts. The results indicate that TGF alpha regulates female reproductive development through two opposing mechanisms: within the brain, it facilitates the neuroendocrine activation of the process; at the ovarian level, it modulates the stimulatory effect of gonadotropin hormones on follicular growth and steroidogenesis. C1 OREGON REG PRIMATE RES CTR,DIV NEUROSCI,BEAVERTON,OR 97006. OREGON HLTH SCI UNIV,DEPT PHYSIOL,PORTLAND,OR 97201. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. TEXAS TECH UNIV,HLTH SCI CTR,DEPT CELL BIOL & ANAT,LUBBOCK,TX 79430. FU NICHD NIH HHS [HD-07438, HD-24870, HD-25123] NR 70 TC 52 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1994 VL 135 IS 4 BP 1392 EP 1400 DI 10.1210/en.135.4.1392 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK877 UT WOS:A1994PK87700015 PM 7925101 ER PT J AU OSTROWSKI, NL LOLAIT, SJ YOUNG, WS AF OSTROWSKI, NL LOLAIT, SJ YOUNG, WS TI CELLULAR-LOCALIZATION OF VASOPRESSIN V1A RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN ADULT MALE-RAT BRAIN, PINEAL, AND BRAIN VASCULATURE SO ENDOCRINOLOGY LA English DT Article ID MICROSCOPIC AUTORADIOGRAPHIC LOCALIZATION; INOSITOL PHOSPHOLIPID-METABOLISM; OXYTOCIN BINDING-SITES; ARGININE-VASOPRESSIN; LATERAL SEPTUM; QUANTITATIVE AUTORADIOGRAPHY; CARDIOVASCULAR REGULATION; SUPRACHIASMATIC NUCLEUS; PARAVENTRICULAR NUCLEUS; HORMONE RECEPTOR AB Vasopressin V1a receptor (V1aR) transcripts were localized in brain, pineal, and superficial brain vascular tissues of adult male rats using hybridization histochemistry and an [S-35]riboprobe complementary to the messenger ribonucleic acid (mRNA) encoding the fifth to the midseventh transmembrane regions of the receptor. V1aR mRNA was extensively distributed throughout brain and was expressed in 1) superficial cells of the granule cell layers of the main olfactory bulb, hippocampal dentate gyrus, and cerebellum; 2) numerous anatomically distinct brain nuclei; 3) isolated cells dispersed throughout the central nervous system; 4) cells of the choroid plexus, occasional blood Vessels in the olfactory bulb and interpeduncular nucleus, and extraparenchymal intracranial vasculature; and 5) some white matter structures. Numerous cells expressing V1aR transcripts were found in forebrain structures, including primary olfactory (piriform) cortex, the anterior and posterior olfactory nuclei; dorsal, intermediate, and ventral lateral septal nuclei; the septo-fimbrial nucleus and accumbens nucleus; and numerous hypothalamic regions with the most intense hypothalamic labeling in the arcuate, stigmoid, suprachiasmatic, and periventricular nuclei and the lateral hypothalamic area. Cells expressing V1aR transcripts were ubiquitous throughout the midbrain, pontine, and medullary regions. A lower intensity signal was found in cells of the parvocellular paraventricular and anteroventral nucleus of the thalamus, circumventricular organs including the pineal, and the subfornical organ. V1aR transcripts were not generally detected in parenchymal vasculature, but could be found over large blood vessels in the interpeduncular nucleus and medial olfactory bulb; transcripts were commonly detected in perivascular brain cells. V1aR mRNA was abundantly expressed by choroid plexus, endothelial cells of midline blood vessels between the main olfactory bulbs, and superficial vascular tissue on all brain surfaces. These data confirm the presence of the vascular/hepatic-type V1aR gene in brain tissue and document an extensive expression. The distribution of V1aR mRNA suggests that there are at least two types of vasopressin-responsive cells in brain: one type exemplified by lateral septal area neurons innervated by classical axodendritic/somatic synaptic vasopressinergic terminals and a second, perivascular/vascular type that would facilitate humoral vasopressinergic signaling in the brain. RP OSTROWSKI, NL (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D-10,BETHESDA,MD 20892, USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 82 TC 204 Z9 207 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 OCT PY 1994 VL 135 IS 4 BP 1511 EP 1528 DI 10.1210/en.135.4.1511 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK877 UT WOS:A1994PK87700030 PM 7925112 ER PT J AU BARRETT, JC AF BARRETT, JC TI CELLULAR AND MOLECULAR MECHANISMS OF ASBESTOS CARCINOGENICITY - IMPLICATIONS FOR BIOPERSISTENCE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Biopersistence of Respirable Synthetic Fibers and Minerals CY SEP 07-09, 1992 CL LYON, FRANCE SP INT AGCY RES CANC, INSERM, CNRS DE TUMOR SUPPRESSOR GENES; PROTOONCOGENES; CHROMOSOMAL MUTATIONS; CELL PROLIFERATION; NEOPLASTIC PROGRESSION ID HUMAN-MALIGNANT MESOTHELIOMA; CHROMOSOMAL-ABNORMALITIES; PLEURAL MESOTHELIOMA; CELLS; TRANSFORMATION; CULTURE; GROWTH; FIBERS; LINES; ESTABLISHMENT AB Carcinogenic agents can influence the carcinogenic process either by mutating critical target genes or by increasing the number of cells at risk for mutations. Cytogenetic and molecular studies of asbestos-related cancers indicate that inactivation or loss of multiple tumor suppressor genes occurs during lung cancer development. Aneuploidy and other chromosomal changes induced by asbestos fibers may be involved in genetic alterations in asbestos-related cancers. Furthermore, asbestos fibers may influence the carcinogenic process by inducing cell proliferation, free radicals, or other promotional mechanisms. Therefore, asbestos fibers may act at multiple stages oi the carcinogenic process by both genetic and epigenetic mechanisms. Biopersistence is undoubtedly important in fiber carcinogenicity. However, the time required for a fiber to remain in the lung to exert a cancer-related effect is difficult to specify. RP BARRETT, JC (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 23 Z9 23 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 SU 5 BP 19 EP 23 DI 10.2307/3432053 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PT108 UT WOS:A1994PT10800005 PM 7882928 ER PT J AU POIRIER, MC BELAND, FA AF POIRIER, MC BELAND, FA TI DNA ADDUCT MEASUREMENTS AND TUMOR-INCIDENCE DURING CHRONIC CARCINOGEN EXPOSURE IN RODENTS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 5th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY OCT 18-21, 1992 CL WURZBURG, GERMANY SP DEUT FORSCHUNGSGEMEINSCH, GERMAN SOC PHARM & TOXICOL, NATL CTR TOXOL RES, JEFFERSON, ARKANSAS, UNIV WURZBURG DE AROMATIC AMINES; 2-ACETYLAMINOFLUORENE; 4-AMINOBIPHENYL; DNA ADDUCTS; TUMORIGENESIS; RATS; MICE; CHRONIC DOSING ID DOSE-RESPONSE RELATIONSHIP; CHEMICAL CARCINOGENESIS; MOLECULAR DOSIMETRY; RAT-LIVER; 2-ACETYLAMINOFLUORENE; AFLATOXIN-B1; MICE; 4-(N-METHYL-N-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; DIETHYLNITROSAMINE; INDUCTION AB In an attempt to elucidate the relationship between DNA adduct formation and tumorigenesis, DNA adducts were measured in the livers and bladders of mice during chronic exposure to several different doses of 2-acetylaminofluorene (2-AAF) and 4-aminobiphenyl (4-ABP). Continuous oral administration of these compounds for 4 weeks produced an increase in DNA adduct formation during the first 2 weeks, followed by a plateau, which presumably occurred because the rate of adduct removal offset the rate of adduct formation. The quantity of DNA adducts present at equilibrium correlated directly with the carcinogen concentration; therefore, when exposure was continued for 4 weeks, DNA adducts that reflected the plateau level at each dose could be expressed as a function of dose, liver and bladder DNA adduct profiles thus obtained during administration of multiple doses of 2-AAF (to female mice) and 4-ABP (to male and female mice) were compared to profiles for tumor incidences obtained during lifetime exposures to the same doses. These experiments demonstrated similar profiles for DNA adduct formation and tumorigenesis in liver. In the bladder, DNA adducts were linear, but tumors only appeared at the higher doses in conjunction with cell proliferation. In addition to these aromatic amines, similar data are available for aflatoxin B-1, diethylnitrosamine, and (methylnitrosamino)-1-(3-pyridyl)-1-butanone (also known as nicotine-derived nitrosoketone). Of the nine different biological situations (carcinogen/species/sex/organ) for which data are available, correlations between steady-state DNA adduct levels and tumorigenic response at the different doses were linear in five of the nine biological models. When the relationship between DNA adduct formation and tumor incidence was not linear, the profiles observed were considered to be the result of tissue-specific phenomena such as metabolic activation, cell proliferation, or cytotoxicity. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP POIRIER, MC (reprint author), NCI,DIV CANC ETIOL,BLDG 37,RM 3B25,BETHESDA,MD 20892, USA. NR 22 TC 37 Z9 38 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 SU 6 BP 161 EP 165 DI 10.2307/3432171 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PT120 UT WOS:A1994PT12000029 PM 7889840 ER PT J AU COIN, PG ROGGLI, VL BRODY, AR AF COIN, PG ROGGLI, VL BRODY, AR TI PERSISTENCE OF LONG, THIN CHRYSOTILE ASBESTOS FIBERS IN THE LUNGS OF RATS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Biopersistence of Respirable Synthetic Fibers and Minerals CY SEP 07-09, 1992 CL LYON, FRANCE SP INT AGCY RES CANC, INSERM, CNRS DE ASBESTOS; CHRYSOTILE; PULMONARY CLEARANCE; PARTICLE TRANSLOCATION; PLEURAL DISEASE ID SHORT-TERM EXPOSURE; CROCIDOLITE ASBESTOS; AMOSITE ASBESTOS; ALVEOLAR MACROPHAGES; MOUSE LUNG; CLEARANCE; INHALATION; PATHOGENICITY; DEPOSITION; TOXICITY AB The distribution of inhaled mineral fibers in the lung determines the site and severity of disease caused by the fibers. Some of our recent work has described the fate of inhaled asbestos fibers in rodents. After a brief inhalation exposure, asbestos fibers are deposited primarily at the first alveolar duel bifurcations, and fibrotic lesions are initiated. These sites of deposition occur as close to the Visceral pleura as 220 mu m. Several studies have suggested that short fibers are cleared from the lung more efficiently than long ones, and our data support this view. Our laboratory has shown that aerosolized chrysotile fibers longer than 16 mu m can be deposited in the peripheral lung parenchyma of rats, and the measured clearance rate of these fibers is not significantly different from zero. Chrysotile, but not amphibole, fibers split longitudinally. so that the number of retained chrysotile fibers greater than or equal to 16 mu m in length increases over time, We have not observed significant changes in chemical composition of chrysotile fibers up to 30 days post-deposition in the rat. Nor have we observed translocation of chrysotile fibers from the ''central'' regions of the lung toward the subpleural regions. However, 1 month after a single 3-hr exposure to chrysotile asbestos, the longest, most pathogenic fibers persist throughout the lung parenchyma. These retained fibers have the potential to cause disease in both parenchyma and pleura. C1 DUKE UNIV,DEPT PATHOL,DURHAM,NC. VET ADM MED CTR,DURHAM,NC. TULANE UNIV,MED CTR,DEPT PATHOL & LAB MED,NEW ORLEANS,LA. RP COIN, PG (reprint author), NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 30 Z9 31 U1 0 U2 2 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 SU 5 BP 197 EP 199 DI 10.2307/3432084 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PT108 UT WOS:A1994PT10800036 PM 7882930 ER PT J AU GANT, TW SCHRENK, D SILVERMAN, JA THORGEIRSSON, SS AF GANT, TW SCHRENK, D SILVERMAN, JA THORGEIRSSON, SS TI REQUIREMENT FOR METABOLIC-ACTIVATION OF ACETYLAMINOFLUORENE TO INDUCE MULTIDRUG GENE-EXPRESSION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 5th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY OCT 18-21, 1992 CL WURZBURG, GERMANY SP DEUT FORSCHUNGSGEMEINSCH, GERMAN SOC PHARM & TOXICOL, NATL CTR TOXOL RES, JEFFERSON, ARKANSAS, UNIV WURZBURG DE MULTIDRUG; RESISTANCE; ACETYLAMINOFLUORENE; METABOLISM; HEPATOCYTES ID SURFACE P-GLYCOPROTEIN; MAMMALIAN-CELL LINES; RESISTANCE MDR1 GENE; YA-SUBUNIT GENE; DRUG-RESISTANCE; CYSTIC-FIBROSIS; RAT-LIVER; CANALICULAR MEMBRANE; RESPONSIVE ELEMENT; COMPLEMENTARY-DNA AB Previously we have demonstrated that several xenobiotics can induce multidrug (mdr) gene expression in cultures of primary isolated hepatocytes. One of the best of these xenobiotic inducers in rat hepatocytes is 2-acetylaminofluorene (2-AAF), which induces mdr expression by an enhancement of mdr gene transcription. In all species studied to date, AAF is extensively and variously metabolized. In this study we have sought to determine if AAF per se or a metabolite is responsible for mediating the increase in mdr gene transcription and expression. This study demonstrates that AAF per se is not active, but that the effect of AAF we have observed on mdr gene transcription and expression in the rat is due to the formation of a reactive metabolite(s). Our data indicate that this reactive metabolite is probably N-acetoxy-2-aminofluorene or the sulfate ester of N-hydroxy-AAF. The requirement for the formation of one of these metabolites may explain the differences in species response to AAF, in terms of mdr gene expression, that we have observed. We hypothesize that the mechanism by which mdr gene transcription is increased in response to AAF involves a covalent interaction between a reactive metabolite and an mdr gene regulatory protein. Our current work is concerned with the exploration of this hypothesis. C1 NCI,BETHESDA,MD 20892. NR 46 TC 6 Z9 6 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 SU 6 BP 209 EP 212 DI 10.2307/3432180 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PT120 UT WOS:A1994PT12000038 PM 7889850 ER PT J AU BARRETT, JC AF BARRETT, JC TI PREVENTION OF ENVIRONMENTALLY RELATED DISEASES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID EXPERIMENTAL-ANIMALS; CANCER; CARCINOGENESIS; RISK RP BARRETT, JC (reprint author), NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,BETHESDA,MD, USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 IS 10 BP 812 EP 813 DI 10.2307/3432106 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PP135 UT WOS:A1994PP13500001 PM 9738204 ER PT J AU ROMAGNOLO, D DIAUGUSTINE, RP AF ROMAGNOLO, D DIAUGUSTINE, RP TI TRANSGENIC APPROACHES FOR MODIFYING THE MAMMARY-GLAND TO PRODUCE THERAPEUTIC PROTEINS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE CHRONIC AND HEREDITARY DISEASES; ENVIRONMENTAL AND HEALTH RESEARCH; GENE EXPRESSION; LACTATION; MAMMARY GLAND; THERAPEUTIC PROTEINS; TRANSGENICS ID HIGH-LEVEL EXPRESSION; ACTIVE HUMAN ALPHA-1-ANTITRYPSIN; PROMOTER DIRECTS EXPRESSION; TISSUE-SPECIFIC GENE; TUMOR VIRUS; HORMONAL-REGULATION; EPITHELIAL-CELLS; HYBRID GENE; MOUSE MILK; WAP GENE AB Bioengineering of the mammary gland to produce proteins of therapeutic and industrial value is the result of extensive investigation of the physiology of the mammary gland and the ability to generate transgenic animals. Targeting the expression of heterologous proteins to mammary tissue requires a thorough understanding of the biochemical events that coordinate growth and differentiation of the mammary gland and of the hormonal and developmental regulation of expression of milk protein genes. The characterization of mammary-specific promoter regions in milk protein genes and knowledge of the mechanisms that confer integration site-independent expression of transgenes have significantly contributed to modifying the mammary gland to produce heterologous proteins of therapeutic interest. The generation of large transgenic farm animals provides the opportunity for large-scale production of proteins in milk that have a therapeutic value but art naturally present at low concentrations in biological fluids. Transgenic mammary epithelial cells offer a versatile research model in biomedical, environmental health, and neonatal toxicology research. RP ROMAGNOLO, D (reprint author), NIEHS, BIOCHEM RISK ANAL LAB, MD4-01, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 62 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 IS 10 BP 846 EP 851 DI 10.2307/3432115 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PP135 UT WOS:A1994PP13500014 PM 9644191 ER PT J AU HAVERKOS, HW KOPSTEIN, AN WILSON, H DROTMAN, P AF HAVERKOS, HW KOPSTEIN, AN WILSON, H DROTMAN, P TI NITRITE INHALANTS - HISTORY, EPIDEMIOLOGY, AND POSSIBLE LINKS TO AIDS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE AIDS; HIV INFECTION; IMMUNOSUPPRESSION; KAPOSIS SARCOMA; NITRITE INHALANTS; SEXUAL BEHAVIOR ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; KAPOSIS-SARCOMA; HOMOSEXUAL MEN; ISOBUTYL NITRITE; AMYL NITRITE; DRUG-USE; INHALATION TOXICITY; VOLATILE NITRITES; VIRUS AB Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. C1 COMM MONITOR POPPERS,SAN FRANCISCO,CA 94102. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,ATLANTA,GA 30333. RP HAVERKOS, HW (reprint author), NIDA,ROOM 10A-38,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 65 TC 29 Z9 32 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1994 VL 102 IS 10 BP 858 EP 861 DI 10.2307/3432118 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PP135 UT WOS:A1994PP13500017 PM 9644194 ER PT J AU BLAZKA, ME TEPPER, JS DIXON, D WINSETT, DW OCONNOR, RW LUSTER, MI AF BLAZKA, ME TEPPER, JS DIXON, D WINSETT, DW OCONNOR, RW LUSTER, MI TI PULMONARY RESPONSE OF FISCHER-344 RATS TO ACUTE NOSE-ONLY INHALATION OF INDIUM TRICHLORIDE SO ENVIRONMENTAL RESEARCH LA English DT Article ID AMINOLEVULINIC-ACID DEHYDRATASE; MACROPHAGE FIBRONECTIN RELEASE; AIRWAY INFLAMMATION; RESPIRATORY-TRACT; GALLIUM-ARSENIDE; LUNG INJURY; CHLORIDE; TOXICITY; OZONE; HYPERRESPONSIVENESS AB We have previously shown that rats dosed intratracheally with indium trichloride (InCl3) develop severe lung damage and fibrosis. However, it is not clear what pulmonary effects would result following accidental occupational exposure to low concentrations of indium by inhalation. The present study uses a model of acute lung injury based on single 1-hr nose-only exposures to 0.2, 2.0, or 20 mg InCl3/m(3). Exposure to 0.2 mg InCl3/m(3) was capable of initiating an inflammatory response. Seven days following inhalation of 20 mg InCl3/m(3) the total cell number, fibronectin, and TNF alpha levels in the bronchial alveolar lavage fluid were 8, 40, and 5 times higher than the control, respectively. Commensurate with the level of lung injury 7 days after exposure, an acute restrictive lung lesion and increased airway responsiveness to acetylcholine were observed. Forty-two days after exposure a compensatory increase in lung Volume and carbon monoxide diffusing capacity in the 20 mg InCl3/m(3) group suggested recovery from the lung injury. Lung collagen levels were increased in a concentration-dependent manner 42 days postexposure. These data indicate that inhalation of InCl3/m(3) causes acute inflammatory changes in the lung. (C) 1994 Academic Press, Inc. C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. RP BLAZKA, ME (reprint author), NIEHS,ENVIROM IMMUNOL & NEUROBIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 13 Z9 14 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1994 VL 67 IS 1 BP 68 EP 83 DI 10.1006/enrs.1994.1065 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA PN459 UT WOS:A1994PN45900005 PM 7925195 ER PT J AU JOHNSTON, JA FERRIS, DK WANG, JM LONGO, DL OPPENHEIM, JJ KELVIN, DJ AF JOHNSTON, JA FERRIS, DK WANG, JM LONGO, DL OPPENHEIM, JJ KELVIN, DJ TI STAUROSPORINE RESTORES SIGNALING AND INHIBITS INTERLEUKIN-8-INDUCED CHEMOTACTIC DESENSITIZATION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE STAUROSPORINE; INTERLEUKIN-8; DESENSITIZATION; N-FORMYL-METHIONYL-LEUCYL-PHENYLALANINE ID NEUTROPHIL-ACTIVATING PEPTIDE-1/INTERLEUKIN-8; PROTEIN-KINASE; RECEPTOR; PHOSPHORYLATION; EXPRESSION; PEPTIDE-2; RHODOPSIN; FAMILY; CELLS AB Interleukin 8 (IL-8) is a chemotactic cytokine (chemokine) that plays a key role in the accumulation and activation of neutrophils at inflammatory sites. In this report we demonstrate that homologous chemotactic desensitization occurs upon pretreatment of neutrophils with IL-8 or N-formyl-methionyl-leucyl-phenylalanine (FMLP) and results in the inhibition of neutrophil chemotaxis upon subsequent challenge with the same ligand. This homologous chemotactic desensitization could be prevented by pretreating the neutrophils with the protein kinase inhibitor staurosporine, indicating that protein kinases may play an essential role. The attenuation of homologous desensitization by staurosporine restored chemotaxis but was not associated with a change in IL-8 receptor expression, affinity or the rate of ligand internalization, indicating that homologous desensitization does not alter ligand-receptor interaction. Using two-dimensional analysis we have shown that IL-8 induced a rapid serine/threonine phosphorylation of a number of neutrophil substrates the most prominent being phosphoprotein 39 (pp39), extracellular signal-related kinase-1, pp55 and pp66. Prior desensitization of neutrophils with IL-8 blocked all subsequent phosphorylation upon rechallenge with IL-8. However, the desensitization was specific for IL-8 since normal phosphorylation of identical substrates was observed in response to FMLP. When neutrophils were pretreated with staurosporine, prior to desensitization, phosphorylation of pp39 was observed upon restimulation with IL-8. Further study revealed that pp55 and pp66 were not phosphorylated in the presence of staurosporine. Thus, homologous desensitization of neutrophils in response to IL-8 does not result from changes in receptor expression, but rather from a staurosporine-sensitive inactivation of subsequent signal transduction. This desensitization is selective since the cells are able to respond to other ligands. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP JOHNSTON, JA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BRMP,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [1-CO-74102] NR 26 TC 18 Z9 18 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1994 VL 24 IS 10 BP 2556 EP 2562 DI 10.1002/eji.1830241044 PG 7 WC Immunology SC Immunology GA PL987 UT WOS:A1994PL98700043 PM 7925583 ER PT J AU WEATHERBY, NL NEEDLE, R CESARI, H BOOTH, R MCCOY, CB WATTERS, JK WILLIAMS, M CHITWOOD, DD AF WEATHERBY, NL NEEDLE, R CESARI, H BOOTH, R MCCOY, CB WATTERS, JK WILLIAMS, M CHITWOOD, DD TI VALIDITY OF SELF-REPORTED DRUG-USE AMONG INJECTION-DRUG USERS AND CRACK COCAINE USERS RECRUITED THROUGH STREET OUTREACH SO EVALUATION AND PROGRAM PLANNING LA English DT Article ID HIGH AGREEMENT; LOW KAPPA; PARADOXES AB This paper examines the validity of self-reported drug use as a measure of behavior change for the evaluation of drug use prevention and HIV risk reduction programs. The results of urinalysis are used to evaluate responses from 154 subjects from 4 cities to questions about drug use in the past 48 hours in the National Institute on Drug Abuse's (NIDA) Risk Behavior Assessment (RBA). This instrument is currently being used in 21 studies throughout the United States. Unlike criminal justice or employment settings where there is a tendency to underreport drug use, participants in this research study acted more like a treatment seeking population and were slightly more likely to report drug use than to be tested positive. Urinalysis and self-reports agreed for 86.3% of the subjects who reported use of some form of cocaine (Kappa = .658) and 84.9% of the heroin users (Kappa = .631). The percentage of subjects reporting drug use and testing negative was somewhat higher than the percentage reporting no use and testing positive for both cocaine (7.8% vs. 5.8%) and heroin (9.7% vs. 5.2%). The results suggest that self-reported drug use in not-in-treatment, noninstitutionalized populations is accurate enough for measuring changes in risk behavior practces. Urinalysis may not be necessary if respondents are asked about their drug use in a nonthreatening manner, and if they are assured of the confidentiality of their results. C1 NIDA,LEXINGTON,KY 40583. UNIV COLORADO,ADDICT RES & TREATMENT SERV,BOULDER,CO 80309. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. RP WEATHERBY, NL (reprint author), UNIV MIAMI,SCH MED,COMPREHENS DRUG RES CTR,1400 NW 10TH AVE,SUITE 212 D93,MIAMI,FL 33136, USA. NR 17 TC 289 Z9 290 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7189 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD OCT-DEC PY 1994 VL 17 IS 4 BP 347 EP 355 DI 10.1016/0149-7189(94)90035-3 PG 9 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA PN686 UT WOS:A1994PN68600002 ER PT J AU SCHLENGER, WE ROLAND, EJ KROUTIL, LA DENNIS, ML MAGRUDER, KM RAY, BA AF SCHLENGER, WE ROLAND, EJ KROUTIL, LA DENNIS, ML MAGRUDER, KM RAY, BA TI EVALUATING SERVICES DEMONSTRATION PROGRAMS - A MULTISTAGE APPROACH SO EVALUATION AND PROGRAM PLANNING LA English DT Article ID DRUG-ABUSE; HEALTH; IMPLEMENTATION AB This paper describes the rationale for and an example of a multistage approach to evaluating services demonstration programs that takes account of the important design limitations often found in such programs. These limitations may include one or more of the following: (a) the lack of control or comparison groups - i.e., there is no requirement for experimental or quasi-experimental design; (b) the lack of a common intervention - i.e., the demonstrations involve multiple projects, each of which is implementing a different intervention; and (c) the lack of common data collection structure across projects. We view the evaluation of services demonstration programs as one step in the broader process through which new interventions are conceived, tested, and ultimately disseminated. We describe an approach to the evaluation of services demonstrations that provides an empirical basis for identifying those projects that appear ''promising'' (i.e., appear to be fulfilling the demonstration's objectives), and then describes a subset of promising projects in detail. Findings from such an evaluation can provide the basis for moving into the next phase, in which the effectiveness of one or more promising models is tested experimentally. As an example of how this approach can be applied, we describe the design of the National Evaluation of Models for Linking Drug Abuse Treatment and Primary Care, the evaluation of a federally-funded services demonstration that was aimed at examining alternative strategies for improving the linkage between the drug abuse treatment and primary care systems. C1 NIMH,SERV RES BRANCH,BETHESDA,MD 20892. RP SCHLENGER, WE (reprint author), RES TRIANGLE INST,CTR SOCIAL RES & POLICY ANAL,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 28 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7189 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD OCT-DEC PY 1994 VL 17 IS 4 BP 381 EP 390 DI 10.1016/0149-7189(94)90038-8 PG 10 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA PN686 UT WOS:A1994PN68600005 ER PT J AU DELANY, PJ FLETCHER, BW LENNOX, RD AF DELANY, PJ FLETCHER, BW LENNOX, RD TI ANALYZING SHELTER ORGANIZATIONS AND THE SERVICES THEY OFFER - TESTING A STRUCTURAL MODEL USING A SAMPLE OF SHELTER PROGRAMS SO EVALUATION AND PROGRAM PLANNING LA English DT Article ID HOMELESS AB Although the need for services for homeless people, including health, substance abuse, and mental health treatment, has been widely documented, very little attention has been paid to the structural demands on shelter organizations that deliver these services. The present paper presents an exploratory study of 192 shelters in 29 cities that provide overnight accommodation to individuals and families using structural equation analysis to analyze the characteristics of the organizational and service delivery system. The resulting model suggests that services and amenities offered within the sample of shelter organizations are best understood as being influenced by organizational structure, as measured by occupational specialization, mediated through the organization's relationship with the external actors. This preliminary model offers researchers, policy makers and program planners a tool for analyzing the organizational needs that are necessary to support different services and amenities. C1 PACIFIC INST RES & EVALUAT,CHAPEL HILL,NC 27516. RP DELANY, PJ (reprint author), NATL INST DRUG ABUSE,TREATMENT SERV RES BRANCH,5600 FISHERS LANE,ROOM 10A-30,ROCKVILLE,MD 20857, USA. NR 28 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7189 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD OCT-DEC PY 1994 VL 17 IS 4 BP 391 EP 398 DI 10.1016/0149-7189(94)90039-6 PG 8 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA PN686 UT WOS:A1994PN68600006 ER PT J AU WEATHERBY, NL NEEDLE, R CESARI, H BOOTH, R MCCOY, CB WATTERS, JK WILLIAMS, M CHITWOOD, DD AF WEATHERBY, NL NEEDLE, R CESARI, H BOOTH, R MCCOY, CB WATTERS, JK WILLIAMS, M CHITWOOD, DD TI VALIDITY OF SELF-REPORTED DRUG-USE AMONG INJECTION-DRUG USERS AND CRACK COCAINE USERS RECRUITED THROUGH STREET OUTREACH - REPLY SO EVALUATION AND PROGRAM PLANNING LA English DT Note C1 NIDA,LEXINGTON,KY 40583. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. UNIV COLORADO,ADDICT RES & TREATMENT SERV,BOULDER,CO 80309. RP WEATHERBY, NL (reprint author), UNIV MIAMI,SCH MED,COMPREHENS DRUG RES CTR,1400 NW 10TH AVE,SUITE 212 D93,MIAMI,FL 33136, USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7189 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD OCT-DEC PY 1994 VL 17 IS 4 BP 431 EP 432 DI 10.1016/0149-7189(94)90044-2 PG 2 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA PN686 UT WOS:A1994PN68600011 ER PT J AU KU, WW GHANAYEM, BI CHAPIN, RE WINE, RN AF KU, WW GHANAYEM, BI CHAPIN, RE WINE, RN TI COMPARISON OF THE TESTICULAR EFFECTS OF 2-METHOXYETHANOL (ME) IN RATS AND GUINEA-PIGS SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article ID ETHYLENE-GLYCOL MONOMETHYL; PROGRAMMED CELL-DEATH; ETHER; TOXICITY; INVITRO; APOPTOSIS; 2-BUTOXYETHANOL; METABOLISM; EXPOSURE; ALCOHOL AB Glycol ethers produce both hemato- and testicular toxicity in animals, which is dependent on both the alkyl chain length and animal species used. Ethylene glycol monobutyl ether (2-butoxyethanol, BE) causes hemolytic anemia in rats but not in guinea pigs, and red blood cells from both guinea pigs and humans are minimally affected in vitro by the active metabolite 2-butoxyacetic acid. This demonstrates the importance of animal species selection for assessing human risk to BE exposure. 2-Methoxyethanol (ME) produces testicular lesions in rats characterized primarily by the degeneration of spermatocytes undergoing meiotic division with minimal or no hemolytic changes. Because of the differential hemolytic response to BE between rats and guinea pigs, the present study addressed whether the testicular response to ME was similarly dichotomous. Adult rats or guinea pigs were given a single dose of either 200 or 300 mg ME/kg by gavage, and testicular and hemolytic changes were assessed 24 hr after treatment. Testis histology in rats showed dose-dependent degeneration of dividing spermatocytes in stage XIV tubules as expected, with only minimal hemolytic changes, also as expected. In contrast, no testicular or hemolytic effects were observed in guinea pigs 24 hr after either single ME dose. In a subsequent study, a single dose or multiple (3 daily) doses of 200 mg MEikg were given, and animals were examined at 4 days after the start of treatment. Testes from rats given both single and multiple ME doses showed, as expected, tubules depleted of spermatocytes and early spermatids. In guinea pigs, spermatocyte degeneration was observed in stage III/IV tubules for both dosing schemes, but was much less severe and widespread and differed from rats in morphological characteristics, specifically in the appearance of nuclear chromatin degeneration. In the rat, degenerating spermatocytes showed uniformly condensed and dispersed chromatin, while in the guinea pig they showed marked chromatin condensation at the nuclear periphery. No hemolytic changes were observed in either species or dosing scheme. In summary, although ME-associated testicular lesions were observed in both species, they differed significantly in onset, characteristics, and severity. Both the nature of the differential testicular response to ME and a comparison to the in vitro human testicular response to the active metabolite 2-methoxyacetic acid are subjects of future study. (C) 1991 Academic Press, Inc. C1 NIEHS,RES TRIANGLE PK,NC 27709. OI Chapin, Robert/0000-0002-5997-1261 NR 28 TC 9 Z9 10 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 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD OCT PY 1994 VL 61 IS 2 BP 119 EP 133 DI 10.1006/exmp.1994.1031 PG 15 WC Pathology SC Pathology GA QG506 UT WOS:A1994QG50600005 PM 7859828 ER PT J AU ASANUMA, C AF ASANUMA, C TI GABAERGIC AND PALLIDAL TERMINALS IN THE THALAMIC RETICULAR NUCLEUS OF SQUIRREL-MONKEYS SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE THALAMIC RETICULAR NUCLEUS; GLOBUS PALLIDUS; SYNAPSE; COLLOIDAL GOLD; MONKEY ID LATERAL GENICULATE-NUCLEUS; GLUTAMIC-ACID-DECARBOXYLASE; NIGRA PARS RETICULATA; ELECTRON-MICROSCOPIC EVIDENCE; PRIMATE GLOBUS PALLIDUS; PERIGENICULATE NUCLEUS; HORSERADISH-PEROXIDASE; SYNAPTIC TERMINALS; SUBSTANTIA-NIGRA; FINE-STRUCTURE AB The ultrastructure of synaptic terminals from the external segment of the globus pallidus and of other synaptic terminals positive for gamma-aminobutyric acid (GABA) was examined in the thalamic reticular nucleus (TRN) of squirrel monkeys. Two GABA-positive terminals types were commonly encountered within the TRN neuropil. The most common type of GABAergic terminals (F terminals) are filled with dispersed pleomorphic synaptic vesicles and clusters of mitochondria. These terminals establish multiple symmetric synapses upon the somata and dendrites of TRN neurons. The external pallidal terminals, labeled with WGA-HRP, arise from thinly myelinated axons and correspond to the medium to large F terminals. A less prevalent population of smaller GABAergic synaptic profiles was also identified. The synaptic profiles in this second group contain considerably fewer pleomorphic synaptic vesicles in small irregular clusters and fewer mitochondria, establish symmetric synapses, are postsynaptic to other axonal terminals, are presynaptic to dendrites and soma, and are unlabeled following pallidal injections of WGA-HRP. RP ASANUMA, C (reprint author), NIMH, ANIM CTR, NEUROPHYSIOL LAB, POB 608, POOLESVILLE, MD 20837 USA. NR 94 TC 34 Z9 34 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 1994 VL 101 IS 3 BP 439 EP 451 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PP136 UT WOS:A1994PP13600009 PM 7531651 ER PT J AU IZUMI, H ONO, M USHIRO, S KOHNO, K KUNG, HF KUWANO, M AF IZUMI, H ONO, M USHIRO, S KOHNO, K KUNG, HF KUWANO, M TI CROSS-TALK OF TUMOR-NECROSIS-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR IN HUMAN MICROVASCULAR ENDOTHELIAL-CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTEIN-KINASE-C; NF-KAPPA-B; MOUSE BALB/3T3 CELLS; MIDDLE T-ANTIGEN; FACTOR RECEPTOR; MESSENGER-RNA; PLASMINOGEN-ACTIVATOR; VASCULAR ENDOTHELIUM; SURFACE RECEPTORS; MOLECULAR-CLONING AB Our previous studies imply that tumor necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF) might share a common signal transduction pathway in human omental microvascular endothelial (HOME) cells. Exposure of cultured HOME cells to TNF-alpha for 10 min enhanced EGF receptor phosphorylation at a rate comparable to EGF. Apparent phosphorylation of tyrosine residues was observed in addition to serine/threonine of the EGF receptor by EGF, but only a slightly if any tyrosine phosphorylation by TNF-alpha. lit vitro kinase activity of EGF receptor was also enhanced by TNF-alpha as well as by EGF. Furthermore, expression of the c-fos gene was enhanced in response to either EGF or TNF-alpha. Pretreatment of HOME cells with EGF for 12 h almost completely blocked the induction of the c-fos gene by EGF and partially blocked the c-fos induction by TNF-alpha. TNF-alpha-induced c-fos gene expression appeared to be partly due to its transactivation of EGF receptor. EGF and TNF-alpha could enhance c-fos gene expression when protein kinase C was down-regulated by phorbol ester myristate (PMA). Gel retardation assay with the NF-KB consensus sequence showed that NF-kappa B binding activity was dramatically activated by TNF-alpha, but not by EGF or PMA. The binding of another transcription factor, AP-1 (Jun/Fos), was enhanced by EGF, TNF-alpha, and PMA, whereas TNF-alpha could still activate AP-1 after longer exposure to EGF. TNF-alpha-induced activation of c-fos gene appears to be mediated through pleiotropic mechanisms and partly through a common signal with EGF, possibly through EGF receptor in microvascular endothelial cells. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,MODIFIERS PROGRAM,FREDERICK,MD 21702. RP IZUMI, H (reprint author), KYUSHU UNIV,SCH MED,DEPT BIOCHEM,FUKUOKA 812,JAPAN. NR 59 TC 28 Z9 28 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT PY 1994 VL 214 IS 2 BP 654 EP 662 DI 10.1006/excr.1994.1303 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PK019 UT WOS:A1994PK01900025 PM 7523156 ER PT J AU JACOBSEN, SEW RUSCETTI, FW OKKENHAUG, C LIEN, E ORTIZ, M VEIBY, OP KELLER, JR AF JACOBSEN, SEW RUSCETTI, FW OKKENHAUG, C LIEN, E ORTIZ, M VEIBY, OP KELLER, JR TI DISTINCT AND DIRECT SYNERGISTIC EFFECTS OF IL-1 AND IL-6 ON PROLIFERATION AND DIFFERENTIATION OF PRIMITIVE MURINE HEMATOPOIETIC PROGENITOR CELLS IN-VITRO SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE IL-1; IL-6; PRIMITIVE PROGENITORS ID COLONY-STIMULATING FACTOR; STEM-CELLS; GROWTH-FACTORS; BONE-MARROW; HPP-CFC; INTERLEUKIN-1; RECEPTORS; SURVIVAL; HEMOPOIETIN-1; CULTURE AB While interleukin-1 (IL-1) and IL-6 have been demonstrated to synergize with colony-stimulating factors (CSFs) and stem cell factor (SCF) to stimulate myeloid colony formation of primitive hematopoietic progenitor cells, it has not yet been established whether these effects are directly mediated. In the present study, direct effects of IL-1 and IL-6 were examined on primitive Lin(-)Sca-1(+) murine bone-marrow progenitor cells that were cultured and plated individually. IL-1 and IL-6 showed not only overlapping, but also distinct, patterns of direct synergy. While IL-1 or IL-6 had no proliferative effects as single growth factors, IL-1, in combination with granulocyte-macrophage CSF (GM-CSF), IL-3, CSF-1, and SCF, but not granulocyte-CSF (G-CSF), enhanced the cloning frequency of Lin(-)Sca-1(+) progenitors three- to five-fold, whereas IL-6 increased the cloning frequency in response to all four CSFs and SCF two- to seven-fold. In all cases, the size of the colonies observed were increased as well. Furthermore, the combined action of IL-1 and IL-6 resulted in additive or synergistic enhancement of CSF- and SCF-stimulated colony formation of Lin(-)Sca-1(+) high proliferative potential colony-forming cells (HPP-CFCs). Finally, IL-6, but not IL-1, enhanced the number of immature blast cells observed in CSF- and SCF-stimulated cultures. C1 NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. PRI DYNCORP,FREDERICK,MD 21701. NYCOMED AS,N-0401 OSLO,NORWAY. RP JACOBSEN, SEW (reprint author), NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT IMMUNOL,MONTEBELLO,N-0310 OSLO,NORWAY. FU NCI NIH HHS [N01-CO-74102] NR 46 TC 18 Z9 19 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 1994 VL 22 IS 11 BP 1064 EP 1069 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PL250 UT WOS:A1994PL25000004 PM 7925772 ER PT J AU MACIEJEWSKI, JP HIBBS, JR ANDERSON, S KATEVAS, P YOUNG, NS AF MACIEJEWSKI, JP HIBBS, JR ANDERSON, S KATEVAS, P YOUNG, NS TI BONE-MARROW AND PERIPHERAL-BLOOD LYMPHOCYTE PHENOTYPE IN PATIENTS WITH BONE-MARROW FAILURE SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE APLASTIC ANEMIA; BONE MARROW; ACTIVATED LYMPHOCYTES ID SEVERE APLASTIC-ANEMIA; HEMATOPOIETIC PROGENITOR CELLS; NATURAL-KILLER CELLS; COLONY FORMATION; MYELODYSPLASTIC SYNDROMES; INTERFERON-GAMMA; NORMAL DONORS; DISEASE; INVITRO; SUPPRESSION AB Patients with aplastic anemia (AA) respond to immunosuppressive therapy, and several lines of laboratory evidence support a role for cell-mediated immunity in the pathogenesis of marrow failure including expansion of cytotoxic T lymphocytes (CTL) in the blood of AA patients, overexpression of inhibitors such as IFN-gamma in the marrow of AA patients, and suppression of hematopoietic cells by CTL in vitro. However, the phenotype of immune effecters in the marrow of AA patients remains unknown. We examined severe (sAA) and moderate AA (mAA) patients and compared them to healthy volunteers and patients with myelodysplastic syndrome (MDS). Our study shows that percentages of HLA-DR(+) CD8(+) lymphocytes and natural killer (NK) cells, CD56(+), were elevated in the marrow of AA patients. Peripheral blood (PB), in all instances, did not reflect changes seen in the bone marrow (BM). Increased percentages of activated CD8(+) cells were found in marrow and blood in 43% of AA patients, but in 28% of AA patients, activation of CD8(+) cells was only detectable in the marrow. During hematopoietic recovery, activated CD8(+) cells and NK cells in marrow declined, but not to normal levels. T cells bearing the gamma delta-phenotype were elevated in the blood of sAA patients (p<0.05) but were not significantly increased in BM from sAA and MDS patients. Percentages of activated immune effecters are increased in the marrow of AA patients as is consistent with a localized immune response in this disease. Marrow phenotyping may be more sensitive than peripheral blood analysis for detecting an abnormal cellular immune response. RP MACIEJEWSKI, JP (reprint author), NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 49 TC 89 Z9 102 U1 1 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 1994 VL 22 IS 11 BP 1102 EP 1110 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PL250 UT WOS:A1994PL25000010 PM 7925777 ER PT J AU HUBBSTAIT, L OSOFSKY, JD HANN, DM CULP, AM AF HUBBSTAIT, L OSOFSKY, JD HANN, DM CULP, AM TI PREDICTING BEHAVIOR PROBLEMS AND SOCIAL COMPETENCE IN CHILDREN OF ADOLESCENT MOTHERS SO FAMILY RELATIONS LA English DT Article DE ADOLESCENT MOTHERS; ATTACHMENT; BEHAVIOR PROBLEMS; MATERNAL DEPRESSION; SOCIAL COMPETENCE ID FOLLOW-UP; SELF-ESTEEM; ATTACHMENT; DEPRESSION; ADJUSTMENT; CONSTRUCT; OUTCOMES; PROGRAMS; TEENAGE; SCHOOL AB This longitudinal investigation evaluated an additive model of the impact of adolescent mothers' parenting practices on their children. Infant-mother attachment predicted behavior problems among preschool children of adolescent mothers. Adolescent mothers' depression explained significant additional variance in those same behavior problems. Adolescent mothers' self-esteem predicted their preschool children's social competence. These findings call for interventions for adolescent mothers and their children that alleviate maternal depression and promote infant secure attachment and maternal self-esteem. C1 LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA 70112. NIMH,ROCKVILLE,MD 20857. NIMH,BEHAV COGNIT & SOCIAL PROC RES BRANCH,ROCKVILLE,MD 20857. RP HUBBSTAIT, L (reprint author), OKLAHOMA STATE UNIV,DEPT FAMILY RELAT & CHILD DEV,STILLWATER,OK 74078, USA. NR 69 TC 51 Z9 51 U1 0 U2 3 PU NATL COUNCIL FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0197-6664 J9 FAM RELAT JI Fam. Relat. PD OCT PY 1994 VL 43 IS 4 BP 439 EP 446 DI 10.2307/585376 PG 8 WC Family Studies; Social Work SC Family Studies; Social Work GA PQ431 UT WOS:A1994PQ43100013 ER PT J AU MAHER, F VANNUCCI, SJ SIMPSON, IA AF MAHER, F VANNUCCI, SJ SIMPSON, IA TI GLUCOSE-TRANSPORTER PROTEINS IN BRAIN SO FASEB JOURNAL LA English DT Review DE GLUCOSE TRANSPORT; CEREBRAL GLUCOSE UTILIZATION; NEURONS; GLIA ID RAT-BRAIN; GENE-EXPRESSION; INSITU HYBRIDIZATION; PRIMARY CULTURES; XENOPUS OOCYTES; SMALL-INTESTINE; GROWTH-FACTOR; GLIAL-CELLS; BARRIER; GLUT3 AB Glucose is the principal energy source for the mammalian brain. The presence of glucose transport proteins is essential to supply glucose to the neurons and glia within the brain. At least three glucose transporter isoforms have now been identified, and are thought to play a significant role, in the brain. This review describes our current understanding of cell-specific glucose transporter expression in brain, which includes GLUT1 (55-kDa form) present at a high concentration at the blood-brain barrier as well as in parenchymal cells (45-kDa form), most likely in astrocytes, GLUT3 expressed in neurons, and GLUT5 in microglia. We discuss some potential implications of this glucose transporter heterogeneity for cerebral metabolic activity. C1 NIDDKD, BETHESDA, MD 20892 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, DEPT PEDIAT, HERSHEY, PA 17033 USA. NR 65 TC 318 Z9 324 U1 2 U2 15 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD OCT PY 1994 VL 8 IS 13 BP 1003 EP 1011 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA PN069 UT WOS:A1994PN06900003 PM 7926364 ER PT J AU CHOI, AMK TUCKER, RW CARLSON, SG WIEGAND, G HOLBROOK, NJ AF CHOI, AMK TUCKER, RW CARLSON, SG WIEGAND, G HOLBROOK, NJ TI CALCIUM MEDIATES EXPRESSION OF STRESS-RESPONSE GENES IN PROSTAGLANDIN A(2)-INDUCED GROWTH ARREST SO FASEB JOURNAL LA English DT Article DE GADD153; GENE EXPRESSION; HEME OXYGENASE; HSP70; C-FOS; EGR-1 ID SHOCK TRANSCRIPTION FACTOR; CELL-CYCLE PROGRESSION; FOS PROTO-ONCOGENE; MESSENGER-RNA; C-FOS; CYCLOPENTENONE PROSTAGLANDINS; ELEVATED EXPRESSION; SKIN FIBROBLASTS; HEME OXYGENASE; DNA DAMAGE AB We have explored the mechanisms involved in the induction of five stress-response genes (heme oxygenase [HO], c-fos, Egr-1; gadd153, and HSP70) in human diploid fibroblasts growth-arrested by treatment with the antiproliferative prostaglandin A(2) (PGA(2)). The kinetics of c-fos and Egr-1 induction were found to be rapid with maximum expression occurring within 60 min of treatment, whereas maximum expression of HO, gadd153, and HSP70 occurred between 4 and 8 h of treatment. Nuclear run-on assays and measurements of mRNA clearance in the presence of actinomycin D demonstrated that increases in both the rates of gene transcription and/or mRNA stability contribute to the genetic response to PGA(2). Although the mechanisms responsible for increasing the mRNA levels differ for the individual genes, additional experiments provided evidence that alterations in intracellular calcium ([Ca2+](i)) levels were important in initiating the genetic response to PGA(2). PGA(2) treatment resulted in a rapid increase in [Ca2+](i) with the dose-response relationship for Ca2+ mobilization consistent with that seen for the induction of all five genes. [Ca2+](i) chelators that attenuate Ca2+ mobilization by PGA(2) also blocked the mRNA induction by PGA(2) treatment. Density-inhibited confluent cells were less responsive than proliferating subconfluent cells with respect to Ca2+ mobilization after PGA(2) treatment. This was correlated with a lower level of gene induction. These studies support the hypothesis that increased Ca2+ mobilization is an early and central event in the signal transduction pathway (or pathways) mediating the activation of genes in response to PGA(2) treatment. C1 NIA,GERONTOL RES CTR,GENE EXPRESS & AGING SECT,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DIV PULM & CRIT CARE,BALTIMORE,MD. JOHNS HOPKINS MED INST,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. FU NIA NIH HHS [K11AG00516] NR 41 TC 46 Z9 47 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 1994 VL 8 IS 13 BP 1048 EP 1054 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA PN069 UT WOS:A1994PN06900009 PM 7926370 ER PT J AU ANASTI, JN KIMZEY, LM DEFENSOR, RA WHITE, B NELSON, LM AF ANASTI, JN KIMZEY, LM DEFENSOR, RA WHITE, B NELSON, LM TI A CONTROLLED-STUDY OF DANAZOL FOR THE TREATMENT OF KARYOTYPICALLY NORMAL SPONTANEOUS PREMATURE OVARIAN FAILURE SO FERTILITY AND STERILITY LA English DT Article DE PREMATURE OVARIAN FAILURE; HYPERGONADOTROPIC AMENORRHEA; DANAZOL ID ANTIBODIES; INDUCTION; INVITRO; TRIAL AB Objective: To determine if the immunomodulatory and gonadotropin-suppressing properties of danazol would improve follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. Design: Prospective, double-blind, crossover trial. Setting: Tertiary care research institution. Interventions: Two intervention phases lasting 4 months each: one phase during which patients received a standardized estrogen and progestin replacement regimen and one phase during which each patient received a twice daily 400 mg oral dose of danazol. Patients: Fifty-two patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 21 to 39 years. Main Outcome Measures: We measured serum E(2) and P levels weekly during the 2 months after each intervention. We defined a serum E(2) > 50 pg/mL (184 pmol/L) as evidence of ovarian follicle function and a P > 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. Results: Of the 46 patients who completed the study, danazol did not significantly enhance ovarian follicle function or the chance of ovulation. Eight patients ovulated after danazol and four patients ovulated after estrogen and progestin. The power to detect a 30% and a 5% ovulation success rate with therapy was 0.80 and 0.90, respectively. Overall, 30 of 46 women (65%) demonstrated ovarian follicle function and 10 women (21%) ovulated. Conclusion: We were unable to demonstrate a statistically significant benefit from the immuno-modulatory and gonadotropin-suppressing effects of danazol in patients with karyotypically normal spontaneous premature ovarian failure. These patients often have spontaneous remission. Thus, controlled studies are required to determine the effectiveness of treatments for this condition. C1 NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NIDDKD,CHEM BIOL LAB,BETHESDA,MD. RP ANASTI, JN (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,GYNECOL RES SECT,BLDG 10,ROOM 10N-262,BETHESDA,MD 20892, USA. NR 25 TC 18 Z9 21 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 1994 VL 62 IS 4 BP 726 EP 730 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PJ405 UT WOS:A1994PJ40500010 PM 7926080 ER PT J AU GROSS, EA MELLICK, PW KARI, FW MILLER, FJ MORGAN, KT AF GROSS, EA MELLICK, PW KARI, FW MILLER, FJ MORGAN, KT TI HISTOPATHOLOGY AND CELL REPLICATION RESPONSES IN THE RESPIRATORY-TRACT OF RATS AND MICE EXPOSED BY INHALATION TO GLUTARALDEHYDE FOR UP TO 13 WEEKS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID F344 RATS; FORMALDEHYDE VAPOR; B6C3F1 MICE; VIRAL-INFECTIONS; TUMOR PREVALENCE; NASAL LESIONS; BODY-WEIGHT; PROLIFERATION; TOXICITY; CARCINOGENICITY AB In addition to being a respiratory tract irritant and cross-linking agent, glutaraldehyde has a number of properties in common with the rodent nasal carcinogen, formaldehyde. The acute and subchronic responses to glutaraldehyde in the respiratory tract of rats and mice were characterized using histopathology and epithelial cell labeling index as end points. Male and female F344 rats and B6C3F1 mice were whole-body exposed for 1 day, 4 days, 6 weeks, or 13 weeks to 0, 62.5, 125, 250, 500, or 1000 ppb glutaraldehyde using a recycling inhalation chamber. The respiratory tract, with special reference to the nose, was examined by light microscopy and histoautoradiography. Unit length labeling index (ULLI) was determined by nuclear thymidine labeling for selected sites, chosen on the basis of histopathology. A small number of animals exposed to 1000 ppb (rats and mice) or 500 ppb (mice) died before the 6-week time point; these deaths were attributed to glutaraldehyde exposure-associated occlusion of the external nares. Treatment-induced lesions, including epithelial erosions, inflammation, and squamous metaplasia, were confined to the anterior third of the nose and were present in both sexes and species. No histopathological evidence of glutaraldehyde-induced responses was observed in the trachea, central airways, or lungs, while the larynx showed minimal changes. There were clear increases in ULLI in association with acute and subacute cytotoxic responses, with similar concentration-response relationships. Neutrophilic infiltration of the squamous epithelium of the nasal vestibule, present in both rats and mice, became progressively more severe with increasing exposure time and was associated with increased ULLI. The latter responses were generally most severe at the higher glutaraldehyde exposure concentrations, while in female mice they were present at all concentrations of glutaraldehyde studied. Lesions induced by glutaraldehyde were more anterior in the nose than those reported for formaldehyde, they differed in character, and no evidence of ''pre-neoplastic'' lesions or karyomegaly, reported for formaldehyde, was observed with glutaraldehyde. (C) 1994 Society of Toxicology. C1 PACIFIC NW LAB, RICHLAND, WA 99352 USA. NIEHS, NATL TOXICOL PROGRAM, CHEM PATHOL BRANCH, RES TRIANGLE PK, NC 27709 USA. RP GROSS, EA (reprint author), CHEM IND INST TOXICOL, POB 12137, RES TRIANGLE PK, NC 27709 USA. NR 47 TC 23 Z9 23 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1994 VL 23 IS 3 BP 348 EP 362 DI 10.1006/faat.1994.1115 PG 15 WC Toxicology SC Toxicology GA PL450 UT WOS:A1994PL45000004 PM 7835535 ER PT J AU CUNNINGHAM, ML ELWELL, MR MATTHEWS, HB AF CUNNINGHAM, ML ELWELL, MR MATTHEWS, HB TI RELATIONSHIP OF CARCINOGENICITY AND CELLULAR PROLIFERATION INDUCED BY MUTAGENIC NONCARCINOGENS VS CARCINOGENS .3. ORGANOPHOSPHATE PESTICIDES VS TRIS(2,3-DIBROMOPROPYL)PHOSPHATE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-Toxicology CY FEB 23-27, 1992 CL SEATTLE, WA SP SOC TOXICOL ID HEPATOCELLULAR PROLIFERATION; CHEMICAL CARCINOGENESIS; DNA-SYNTHESIS; RAT-LIVER; HEPATOCARCINOGENICITY; INITIATION; METHYLATION; TOXICITY; RODENTS; INVIVO AB Our laboratory has been examining the mechanisms whereby chemicals produce mutagenicity in short-term in vitro assays yet fail to produce carcinogenesis in 2-year rodent bioassays. Previous studies indicated that some mutagenic hepatocarcinogens increased cell proliferation in the target organ, the liver, while other structurally related mutagens that were noncarcinogenic failed to do so. We demonstrate in this report that another mutagenic carcinogen, tris(2,3-dibromopropyl phosphate), increased eel proliferation that was localized in the outer medulla of the kidney. This was also the target site for carcinogenesis in a 2-year bioassay and is another example of the association between chemically induced cell proliferation and carcinogenesis. This study also reports the absence of increased cell proliferation in the liver or kidney after exposure in the diet to the mutagenic organophosphate insecticides dimethoate, dioxathion, and dichlorvos following dietary exposure for 2 weeks at the same dose levels and routes of exposure that did not increase the tumor incidence in either organ in 2-year carcinogenesis assays. The present studies support the tenet that chemically induced cell proliferation may be a necessary prerequisite for chemical carcinogenesis, since in rat liver and kidney there was neither cell proliferation after 2 weeks nor tumor development after 2 years dietary exposure to the mutagenic organophosphate insecticides dimethoate, dioxathion, and dichlorvos. (C) 1994 Society of Toxicology. C1 NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. RP CUNNINGHAM, ML (reprint author), NIEHS,CHEM BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 24 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1994 VL 23 IS 3 BP 363 EP 369 DI 10.1006/faat.1994.1116 PG 7 WC Toxicology SC Toxicology GA PL450 UT WOS:A1994PL45000005 PM 7835536 ER PT J AU VANDENHEUVEL, JP CLARK, GC TRITSCHER, AM LUCIER, GW AF VANDENHEUVEL, JP CLARK, GC TRITSCHER, AM LUCIER, GW TI ACCUMULATION OF POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS IN LIVER OF CONTROL LABORATORY RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Note AB Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls belong to a class of compounds, the polyhalogenated aromatic hydrocarbons (PHAHs), which are ubiquitous environmental contaminants. Due to the existence of a common mechanism of action, i.e., binding to the Ah receptor, the activity of members of this class of compounds is generally expressed relative to the prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as toxic equivalency factors (TEFs). In the present studies we examined the presence of PCDDs and PCDFs in standard laboratory feed and in the liver of untreated rats at three different ages (60, 140, and 200 days) in terms of concentration and in toxic equivalents (TEQs, TEF x concentration). Feed was shown to contain trace amounts of PCDDs and PCDFs and control rat liver was shown to contain several PCDD and PCDF congeners in terms of concentration of congener and concentration of TEQs contributed by that congener. The total concentration of TEQs increased with increasing age in rat liver, going from 20 ppt TEQ at 60 days to 78 ppt TEQ at 200 days of age. This accumulation in dioxin-like activity was due primarily to PCDFs. In particular the congener 2,3,4,7,8-pentachlorodibenzofuran accrued in untreated rat liver accounting for approximately 80% of the total TEQ at 200 days of age. These studies affirm the pervasive presence of PHAHs and suggest prudence in evaluating chronic rat studies in which interference from background levels of PCDDs and PCDFs may be a factor. (C) 1994 Society of Toxicology. RP VANDENHEUVEL, JP (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1994 VL 23 IS 3 BP 465 EP 469 DI 10.1006/faat.1994.1128 PG 5 WC Toxicology SC Toxicology GA PL450 UT WOS:A1994PL45000017 PM 7835546 ER PT J AU POVOSKI, SP ZHOU, WG LONGNECKER, DS JENSEN, RT MANTEY, SA BELL, RH AF POVOSKI, SP ZHOU, WG LONGNECKER, DS JENSEN, RT MANTEY, SA BELL, RH TI STIMULATION OF IN-VIVO PANCREATIC GROWTH IN THE RAT IS MEDIATED SPECIFICALLY BY WAY OF CHOLECYSTOKININ-A RECEPTORS SO GASTROENTEROLOGY LA English DT Review ID SOYBEAN TRYPSIN-INHIBITOR; EXOCRINE PANCREAS; ACINAR-CELLS; CCK-ANTAGONIST; EXOGENOUS CHOLECYSTOKININ; INOSITOL PHOSPHATES; PROTEASE INHIBITOR; SUCKLING RATS; B RECEPTORS; GASTRIN AB Background/Aims: Cholecystokinin (CCK) and gastrin stimulate growth of rodent pancreas in vivo. However, it remains unclear whether these growth effects are mediated specifically by CCK-A receptors, CCK-B receptors, or both. To clarify this issue, the present study examined the effect of highly selective and biologically active CCK agonists on pancreatic growth. Methods: Rats were subcutaneously injected with either (1) CCK-8, a nonselective CCK agonist (2.50 mu g/kg body wt); (2) A-71623, a selective CCK-A agonist, tert-butyl-oxycarbonyl-Trp-Lys(epsilon-N-2-methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 (1.84 mu g/kg body wt); (3) SNF-8815; a selective CCK-B agonist, [(2R,3S)-beta-MePhe(28), N-MeNle(31)]CCK26-33 (2.40 mu g/kg body wt); or (4) saline (control) for 21 days. Rats were killed, and pancreatic weight, protein content, RNA content, DNA content, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mitoses per 10,000 acinar cells were determined. Results: Nonselective CCK agonist significantly increased pancreatic weight, protein, RNA, and DNA contents, and number of mitoses per 10,000 acinar cells. Likewise, selective CCK-A agonist significantly increased pancreatic weight, protein, RNA, and DNA contents, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mitoses per 10,000 acinar cells. In contrast, selective and biologically active CCK-B agonist had no effect. Conclusion: These findings indicate that pancreatic growth is mediated specifically by CCK-A receptors in the rat in vivo. C1 UNIV CINCINNATI,COLL MED,DEPT SURG,CINCINNATI,OH 45267. VET AFFAIRS MED CTR,CINCINNATI,OH. DARTMOUTH COLL,SCH MED,DEPT PATHOL,HANOVER,NH. NIDDK,DIGEST DIS BRANCH,BETHESDA,MD. RI Povoski, Stephen/E-3887-2011 NR 104 TC 43 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 1994 VL 107 IS 4 BP 1135 EP 1146 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PJ586 UT WOS:A1994PJ58600027 PM 7523219 ER PT J AU OLLER, AR SCHAAPER, RM AF OLLER, AR SCHAAPER, RM TI SPONTANEOUS MUTATION IN ESCHERICHIA-COLI CONTAINING THE DNAE911 DNA-POLYMERASE ANTIMUTATOR ALLELE SO GENETICS LA English DT Article ID LACI GENE; COLONY HYBRIDIZATION; MISMATCH REPAIR; MUTAGENESIS; SPECIFICITY; BACTERIOPHAGE-T4; REPLICATION; MECHANISMS; STRAINS; REPRESSOR AB We have previously isolated mutants of Escherichia coli that replicate their DNA with increased fidelity. These mutants have a mutation in the dnaE gene, encoding the cu subunit of DNA polymerase III. They were isolated in a mismatch-repair-defective mutL background, in which mutations can be considered to represent uncorrected DNA replication errors. In the present study we analyze the effect of one of these alleles, dnaE911, an spontaneous mutagenesis in a mismatch-repair-proficient background. In this background, spontaneous mutations may be the sum of uncorrected replication errors and mutations resulting from other pathways. Hence, the effect of the dnaE allele may provide insights into the contribution of uncorrected DNA replication errors to spontaneous mutation. The data show that dnaE911 decreases the level of Rifr, lad and galK mutations in this background by 1.5-2-fold. DNA sequencing of 748 forward mutants in the lad gene reveals that this effect has a clear specificity. Transversions are decreased by similar to 3-fold, whereas transitions, frameshifts, deletions and duplications remain essentially unchanged. Among the tranversions, A.T --> T.A are affected most strongly (similar to 6-fold). In addition to this effect on transversions within the lacI gene, one previously recognized A.T --> G.C base-pair substitution hotspot in the lac operator is also reduced (similar to 5-fold). The data are discussed in the light of the role of DNA replication errors in spontaneous mutation, as well as other possible explanations for the observed antimutator effects. RP OLLER, AR (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 24 Z9 24 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1994 VL 138 IS 2 BP 263 EP 270 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA PH854 UT WOS:A1994PH85400004 PM 7828810 ER PT J AU MOORE, KJ SWING, DA COPELAND, NG JENKINS, NA AF MOORE, KJ SWING, DA COPELAND, NG JENKINS, NA TI THE MURINE DILUTE SUPPRESSOR GENE ENCODES A CELL AUTONOMOUS SUPPRESSOR SO GENETICS LA English DT Article ID COAT-COLOR PHENOTYPE; BRAIN MYOSIN-V; UNCONVENTIONAL MYOSIN; MOUSE; KINESIN; DSU; LOCALIZATION; ORGANIZATION; TRANSPORT; MUTATIONS AB The murine dilute suppressor gene (dsu) suppresses the coat-color phenotype of three pigment mutations, dilute (d), ashen (ash) and leaden (ln), that each produce adendritic melanocytes. Suppression is due to the ability of dsu to partially restore (ash and ln), or almost completely rescore (d), normal melanocyte morphology. While the ash and ln gene products have yet to be identified, the d gene encodes a novel myosin heavy chain (myosin 12), which is speculated to be necessary for the elaboration, maintenance, and/or function of melanocyte cell processes. To begin to discriminate between different models of dsu action, we have produced aggregation chimeras between mice homozygous for dsu and mice homozygous for d to determine if dsu acts cell autonomously or cell nonautonomously. In addition, we have further refined the map location of dsu in order to examine a number of possible dsu candidate genes mapping in the region and to provide a genetic basis for the positional cloning of dsu. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 35 TC 12 Z9 12 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1994 VL 138 IS 2 BP 491 EP 497 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PH854 UT WOS:A1994PH85400024 PM 7828830 ER PT J AU CLAVERIE, JM AF CLAVERIE, JM TI A STREAMLINED RANDOM SEQUENCING STRATEGY FOR FINDING CODING EXONS SO GENOMICS LA English DT Article ID DNA-SEQUENCE; SIMILARITY SEARCH; HUMAN GENOME; LARGE-SCALE; PROTEIN; REGIONS; SELECTION; GENES; IDENTIFICATION; MOLECULES AB The random (shotgun) DNA sequencing strategy is used for most large-scale sequencing projects, including the identification of human disease genes after positional cloning. The principle of the method-sequence assembly from overlap-requires the candidate gene region to be partitioned into 15- to 20-kb pieces (usually lambda inserts), themselves randomly subcloned into M13 prior to sequencing with a 6- to 8-fold redundancy. Most often, a time-consuming directed strategy must be invoked to close the remaining gaps. Ultimately, computer-based methods are invoked to locate putative coding exons within the finished genomic sequence. Given the small average size of vertebrate exons, I show here that they can be detected from the computer analysis of the individual runs, much before completion of contiguity. However, the successful assessment of coding potential from the raw data depends on a combination of new sequence masking techniques. When the identification of coding exons is the primary goal, the usual random sequencing strategy can thus be greatly optimized. The streamlined approach requires only a 2- to 2.5-fold sequencing re dundancy, can dispense with the subcloning in lambda and the closure of gaps, and can be fully automated. The feasibility of this strategy is demonstrated using data from the X-linked Kallmann syndrome gene region. (C) 1994 Academic Press, Inc. RP CLAVERIE, JM (reprint author), NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, 8600 ROCKVILLE PIKE, BETHESDA, MD 20894 USA. NR 39 TC 24 Z9 24 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 EI 1089-8646 J9 GENOMICS JI Genomics PD OCT PY 1994 VL 23 IS 3 BP 575 EP 581 DI 10.1006/geno.1994.1545 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PN753 UT WOS:A1994PN75300009 PM 7851885 ER PT J AU RICHARD, I BROUX, O CHIANNILKULCHAI, N FOUGEROUSSE, F ALLAMAND, V BOURG, N BRENGUIER, L DEVAUD, C PASTURAUD, P ROUDAUT, C LORENZO, F SEBASTIANIKABATCHIS, C SCHULTZ, RA POLYMEROPOULOS, MH GYAPAY, G AUFFRAY, C BECKMANN, JS AF RICHARD, I BROUX, O CHIANNILKULCHAI, N FOUGEROUSSE, F ALLAMAND, V BOURG, N BRENGUIER, L DEVAUD, C PASTURAUD, P ROUDAUT, C LORENZO, F SEBASTIANIKABATCHIS, C SCHULTZ, RA POLYMEROPOULOS, MH GYAPAY, G AUFFRAY, C BECKMANN, JS TI REGIONAL LOCALIZATION OF HUMAN-CHROMOSOME-15 LOCI SO GENOMICS LA English DT Article ID HUMAN GENOME; MARFAN-SYNDROME; PRADER-WILLI; PROTEIN 4.2; GENE; SEQUENCE; CDNA; HYBRIDIZATION; DEFICIENCY; DELETIONS AB One hundred forty-nine chromosome 15 loci were mapped by PCR with respect to chromosome breakpoints in three somatic cell hybrids retaining total or part of chromosome 15 and to a 10-Mb YAC contig. This chromosome was subdivided into 5 regions, yielding an average resolution of more than 1 sequence tagged site per megabase. The mapped loci included 18 genes, 60 cDNA-derived sequence tagged sites, and 69 microsatellites. In addition, the amount of chromosome 15 retained in line A15.1 has been defined. This work represents the first attempt at an integration of the human physical, expression, and genetic maps of chromosome 15. (C) 1994 Academic Press, Inc. C1 CTR ETUD POLYMORPHISME HUMAIN,FDN JEAN DAUSSET,F-75010 PARIS,FRANCE. GENETHON,DEPT LOCALIZAT,F-91000 EVRY,FRANCE. GENETHON,GENEXPRESS PROGRAM,F-91000 EVRY,FRANCE. GENETHON,DEPT GENET MAPPING,F-91000 EVRY,FRANCE. UNIV TEXAS,SW MED CTR DALLAS,DALLAS,TX 75235. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CNRS,UPR 420,F-94801 VILLEJUIF,FRANCE. RI Beckmann, Jacques S /A-9772-2008; Richard, isabelle/J-8298-2013 OI Beckmann, Jacques S /0000-0002-9741-1900; NR 45 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 1994 VL 23 IS 3 BP 619 EP 627 DI 10.1006/geno.1994.1550 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PN753 UT WOS:A1994PN75300014 PM 7851890 ER PT J AU WANG, M KIM, IG STEINERT, PM MCBRIDE, OW AF WANG, M KIM, IG STEINERT, PM MCBRIDE, OW TI ASSIGNMENT OF THE HUMAN TRANSGLUTAMINASE-2 (TGM2) AND TRANSGLUTAMINASE-3 (TGM3) GENES TO CHROMOSOME-20Q11.2 SO GENOMICS LA English DT Note ID LOCALIZATION; MOUSE C1 NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 13 TC 22 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 1994 VL 23 IS 3 BP 721 EP 722 DI 10.1006/geno.1994.1571 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PN753 UT WOS:A1994PN75300035 PM 7851911 ER PT J AU COLANGELO, AM FINK, DW RABIN, SJ MOCCHETTI, I AF COLANGELO, AM FINK, DW RABIN, SJ MOCCHETTI, I TI INDUCTION OF NERVE GROWTH-FACTOR RESPONSIVENESS IN C6-2B GLIOMA-CELLS BY EXPRESSION OF TRKA PROTOONCOGENE SO GLIA LA English DT Article DE HIGH AND LOW AFFINITY NGF RECEPTOR; TRK PHOSPHORYLATION; PC12 CELLS; SNT PHOSPHORYLATION; K-252A; BFGF ID TYROSINE KINASE-ACTIVITY; ADRENERGIC-RECEPTOR ACTIVATION; MESSENGER-RNA CONTENT; PROTOONCOGENE PRODUCT; LOW-AFFINITY; PC12 CELLS; ASTROCYTOMA-CELLS; NGF RECEPTOR; RAT; DIFFERENTIATION AB Cells that lack the high affinity receptor component (trkA) for nerve growth factor (NGF) are unresponsive to NGF. We investigated whether C6-2B cells, a rat glioma derived cell line, express trkA and, as a consequence, are responsive to NGF. In these cells, NGF (100 ng/ml) failed to induce the mRNA encoding for c-fos protooncogene and the low affinity NGF receptor p75(NGFR), two NGF-responsive genes. In contrast, both mRNAs were induced in PC12 cells by NGF. Using a RNase protection assay with a cRNA probe for rat trkA, the expected trkA RNA protected fragment was detected in PC12 but not in C6-2B glioma cells, indicating that C6-2B cells either do not express the gene or express it only in low amounts. Cross-linking of I-125-labeled NGF to PC12 cells identified two major bands with an apparent molecular weight of 158 kDa and 100 kDa corresponding to trkA and p75(NGFR), respectively. In contrast, only the 100 kDa band could be detected in C6-2B cells by cross-linking analysis. In C6-2B cells stably transfected with the rat trkA cDNA, NGF increased c-fos mRNA, induced tyrosine phosphorylation of gp140(trk), and SNT (suc-associated neurotrophic factor-induced tyrosine-phosphorylated target), and caused morphological changes within 72 h. All of these effects of NGF were blocked by the protein kinase inhibitor K-252a suggesting that NGF signal transduction was restored by trkA expression. Most important, in C6trk(+) cells, NGF was a weaker (2-fold) inducer of [H-3]thymidine incorporation when compared to bFGF (5-fold), suggesting that expression of trkA fails to confer to NGF a strong mitogenic effect. Our findings indicate that C6-2B glioma cells do not possess high affinity NGF receptor and thus are unresponsive to NGF and that expression of trkA in neuroectoderm derived cells elicits some of the NGF responses characteristic of neuronal cells. (C) 1994 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,SCH MED,DEPT CELL BIOL,DIV NEUROBIOL,WASHINGTON,DC 20007. NICHHD,GROWTH FACTORS SECT,BETHESDA,MD. OI COLANGELO, ANNA MARIA/0000-0002-7971-4289 FU NINDS NIH HHS [NS 29664, NS 01675] NR 47 TC 23 Z9 23 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 0894-1491 J9 GLIA JI Glia PD OCT PY 1994 VL 12 IS 2 BP 117 EP 127 DI 10.1002/glia.440120205 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PM664 UT WOS:A1994PM66400004 PM 7868185 ER PT J AU REMMENGA, SW COLCHER, D GANSOW, O PIPPEN, CG RAUBITSCHEK, A AF REMMENGA, SW COLCHER, D GANSOW, O PIPPEN, CG RAUBITSCHEK, A TI CONTINUOUS-INFUSION CHEMOTHERAPY AS A RADIATION-ENHANCING AGENT FOR YTTRIUM-90-RADIOLABELED MONOCLONAL-ANTIBODY THERAPY OF A HUMAN TUMOR XENOGRAFT SO GYNECOLOGIC ONCOLOGY LA English DT Article ID RADIOLABELED ANTIBODIES; DOSE FRACTIONATION; OVARIAN-CANCER; COLON CANCER; X-RAYS; RADIOIMMUNOTHERAPY; 5-FLUOROURACIL; CARCINOMA; B72.3; CELLS AB Radioimmunotherapy using monoclonal antibodies is a promising investigational treatment modality for solid tumors. Use of radiation-enhancing agents could significantly impact on the therapeutic response of this treatment. We evaluated the potential interaction of a known radiation-enhancing agent, 5-fluorouracil (5-FU), with the radioimmunotherapeutic effect of a yttrium-90 (Y-90)-labeled monoclonal antibody in a human adenocarcinoma xenograft. Athymic mice were inoculated subcutaneously with the human colon carcinoma cell line LS-174T. All mice had intraperitoneal 3-day osmotic infusion pumps placed by laparotomy. Half of the pumps were filled with 0.9% saline solution and half were filled with a solution containing 5-FU. Three activity levels of Y-90-radiolabeled CC49 antibody were injected into tail veins of the mice. Each activity level was injected into a group of animals with saline-filled pumps and a group with 5-FU-filled pumps. A significant interaction between treatment group and time was found suggesting that the rate of tumor growth for the group of animals receiving Y-90 at 100 muCi plus 5-FU compared to the group of animals receiving Y-90 alone was significantly delayed (P = 0.0055), showing a radiation enhancing effect by 5-FU. These results suggest that the addition of the radiation-enhancing agent 5-FU to radiolabeled antibody may increase the ability to treat solid tumors. Further investigations with other antibodies, radionuclides, and tumor models are indicated. (C) 1994 Academic Press, Inc. C1 NCI,RADIAT ONCOL BRANCH,CHEM SECT,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,DEPT RADIOIMMUNOTHERAPY,DUARTE,CA 91010. UNIV NEBRASKA,MED CTR,DEPT PATHOL MICROBIOL,OMAHA,NE 68101. RP REMMENGA, SW (reprint author), USN,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,PORTSMOUTH,VA 23708, USA. NR 42 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 1994 VL 55 IS 1 BP 115 EP 122 DI 10.1006/gyno.1994.1259 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA PP046 UT WOS:A1994PP04600024 PM 7959251 ER PT J AU ADAMS, DH AFFORD, S KEOGH, A SHAW, S HUBSCHER, S AF ADAMS, DH AFFORD, S KEOGH, A SHAW, S HUBSCHER, S TI EXPRESSION OF MACROPHAGE INFLAMMATORY PROTEIN (MIP)-1-ALPHA AND MIP-1-BETA IN HUMAN LIVER ALLOGRAFTS - A MECHANISM FOR T-CELL RECRUITMENT DURING GRAFT-REJECTION SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV BIRMINGHAM,LIVER UNIT,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. NCI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 20 IS 4 BP A136 EP A136 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600158 ER PT J AU BODENHEIMER, HC LINDSAY, KL DAVIS, GL LEWIS, IH THUNG, SN MAHANEY, K SEEFF, L AF BODENHEIMER, HC LINDSAY, KL DAVIS, GL LEWIS, IH THUNG, SN MAHANEY, K SEEFF, L TI TOLERANCE AND EFFICACY OF ORAL RIBAVIRIN TREATMENT OF CHRONIC HEPATITIS-C - A MULTICENTER TRIAL SO HEPATOLOGY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV FLORIDA,GAINESVILLE,FL 32611. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NIH,BETHESDA,MD 20892. VET AFFAIRS MED CTR,WASHINGTON,DC. NR 0 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A207 EP A207 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600439 ER PT J AU CHAMULITRAT, W BLAZKA, ME JORDAN, SJ LUSTER, MI MASON, RP AF CHAMULITRAT, W BLAZKA, ME JORDAN, SJ LUSTER, MI MASON, RP TI TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE PRODUCTION IN RATS ADMINISTERED CARBON-TETRACHLORIDE SO HEPATOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. LSU,MED CTR,DEPT PHYSIOL,NEW ORLEANS,LA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A338 EP A338 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600963 ER PT J AU CONJEEVARAM, HS KLEINER, DE SALLIE, R MARRONE, A DIBISCEGLIE, AM HOOFNAGLE, JH AF CONJEEVARAM, HS KLEINER, DE SALLIE, R MARRONE, A DIBISCEGLIE, AM HOOFNAGLE, JH TI GROUND GLASS HEPATOCYTES IN CHRONIC HEPATITIS-B - CHANGES WITH ALPHA-INTERFERON THERAPY SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A299 EP A299 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600805 ER PT J AU DIBISCEGLIE, AM CHUNG, YW DAILEY, PJ SHAKIL, AO KRAWCZYNSKI, K HOOFNAGLE, JH AF DIBISCEGLIE, AM CHUNG, YW DAILEY, PJ SHAKIL, AO KRAWCZYNSKI, K HOOFNAGLE, JH TI HEPATITIS-C VIRAL (HCV) MARKERS IN SERUM AND LIVER OF CHRONICALLY INFECTED PATIENTS SO HEPATOLOGY LA English DT Meeting Abstract C1 ST LOUIS UNIV,ST LOUIS,MO 63103. CHIRON CORP,EMERYVILLE,CA. CTR DIS CONTROL,ATLANTA,GA 30333. NIH,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A236 EP A236 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600554 ER PT J AU DIBISCEGLIE, AM KUHNS, MC MCNAMARA, A HOOFNAGLE, JH AF DIBISCEGLIE, AM KUHNS, MC MCNAMARA, A HOOFNAGLE, JH TI CORRELATION BETWEEN HEPATIC AND SEROLOGIC MARKERS OF HBV INFECTION IN PTS WITH CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Meeting Abstract C1 ST LOUIS UNIV,ST LOUIS,MO 63103. ABBOTT LABS,ABBOTT PK,IL. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A296 EP A296 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600796 ER PT J AU ESPOSTI, SD LOFFREDA, S KRESINA, T THOMPSON, N ZERN, M AF ESPOSTI, SD LOFFREDA, S KRESINA, T THOMPSON, N ZERN, M TI LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) ISOFORMS IN LIVER FIBROSIS SO HEPATOLOGY LA English DT Meeting Abstract C1 BROWN UNIV,PROVIDENCE,RI 02912. NIDDK,BETHESDA,MD. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A291 EP A291 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600775 ER PT J AU FARCI, P MUNOZ, S ALTER, H SHIMODA, A GOVINDARAJAN, S CHUNG, L SHIH, J PURCELL, RH AF FARCI, P MUNOZ, S ALTER, H SHIMODA, A GOVINDARAJAN, S CHUNG, L SHIH, J PURCELL, RH TI HEPATITIS-C VIRUS (HCV) ASSOCIATED FULMINANT-HEPATITIS AND ITS TRANSMISSION TO A CHIMPANZEE SO HEPATOLOGY LA English DT Meeting Abstract C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RANCHO LOS AMIGOS MED CTR,DOWNEY,CA 90242. NR 0 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 OCT PY 1994 VL 20 IS 4 BP A265 EP A265 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600670 ER PT J AU FARCI, P MANDAS, A ORIGIANA, G STRAZZERA, A DEGIOANNIS, D PEDDIS, G CHUNG, I MILLER, RH SHIH, J ALLING, D ALTER, H PURCELL, RH BALESTRIERI, A AF FARCI, P MANDAS, A ORIGIANA, G STRAZZERA, A DEGIOANNIS, D PEDDIS, G CHUNG, I MILLER, RH SHIH, J ALLING, D ALTER, H PURCELL, RH BALESTRIERI, A TI MOLECULAR EPIDEMIOLOGY OF INTRAFAMILIAL TRANSMISSION OF HEPATITIS-C VIRUS - A CONTROLLED-STUDY SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV CAGLIARI,DEPT INTERNAL MED,I-09100 CAGLIARI,ITALY. NIAID,DIV INFECT DIS,BETHESDA,MD 20892. NIAID,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A249 EP A249 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600605 ER PT J AU HADZIYANNIS, E HARRISON, J PALAMAROU, C PAVLAKIS, GN HADZIYANNIS, SJ AF HADZIYANNIS, E HARRISON, J PALAMAROU, C PAVLAKIS, GN HADZIYANNIS, SJ TI EXPRESSION OF INTERFERON AND AN INTERFERON-INDUCIBLE GENE IN THE PBMC OF PATIENTS WITH CHRONIC VIRAL-HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. HIPPOKRATION HOSP,ACAD DEPT MED,ATHENS,GREECE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A207 EP A207 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600440 ER PT J AU HAYASHI, P MARRONE, A KLEINER, D CONJEEVARAM, H MAHANEY, K HOOFNAGLE, JH SALLIE, R AF HAYASHI, P MARRONE, A KLEINER, D CONJEEVARAM, H MAHANEY, K HOOFNAGLE, JH SALLIE, R TI HEPATIC APOPTOSIS IN CHRONIC HEPATITIS-C - ANALYSIS BY IN-SITU TERMINAL TRANSFERASE LABELING (TDTL) SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. NCI,EXTRACELLULAR PATHOL LAB,BETHESDA,MD 20892. NR 0 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 OCT PY 1994 VL 20 IS 4 BP A160 EP A160 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600255 ER PT J AU HSIA, CC SCUDAMORE, CH TABOR, E AF HSIA, CC SCUDAMORE, CH TABOR, E TI ABNORMAL EXPRESSION OF THE C-MYC, P53, RB, AND TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) GENES AND PROGNOSIS IN HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. VANCOUVER GEN HOSP,VANCOUVER V5Z 1M9,BC,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A273 EP A273 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600704 ER PT J AU KAZACHKOV, Y KHAOUSTOV, V YOFFE, B SOLOMON, H KLINTMALM, GBG TABOR, E AF KAZACHKOV, Y KHAOUSTOV, V YOFFE, B SOLOMON, H KLINTMALM, GBG TABOR, E TI HEPATOCELLULAR-CARCINOMA IN THE USA - ABNORMALITIES OF THE P53 TUMOR-SUPPRESSOR GENE SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. BAYLOR COLL MED,VAMC,HOUSTON,TX 77030. BAYLOR UNIV,MED CTR,DALLAS,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A364 EP A364 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55601065 ER PT J AU KHARE, M EVERHART, JE MAURER, KR HILL, MC AF KHARE, M EVERHART, JE MAURER, KR HILL, MC TI PREVALENCE OF GALLSTONE DISEASE IN THE UNITED-STATES SO HEPATOLOGY LA English DT Meeting Abstract C1 NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. NIDDK,BETHESDA,MD. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 20 IS 4 BP A118 EP A118 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600085 ER PT J AU LAU, D MOSTOWSKI, H HOOFNAGLE, JH SALLIE, R AF LAU, D MOSTOWSKI, H HOOFNAGLE, JH SALLIE, R TI NUCLEOSIDE ANALOG TOXICITY AND MITOCHONDRIA SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. US FDA,CTR BIL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A189 EP A189 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600370 ER PT J AU LEVINE, ES COLACINO, JM BOWSHER, RR SALLIE, R LEWIS, W AF LEVINE, ES COLACINO, JM BOWSHER, RR SALLIE, R LEWIS, W TI FIAU INCORPORATES INTO DNA FROM HUMAN LIVER AND FROM HUMAN HEPATOBLASTOMA CELLS SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV CINCINNATI,MED CTR,DEPT PATHOL,CINCINNATI,OH 45267. NIDDK,BETHESDA,MD. ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285. NR 0 TC 2 Z9 2 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 OCT PY 1994 VL 20 IS 4 BP A189 EP A189 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600369 ER PT J AU MANGIA, A MUSHAWAR, IK BERKENMEYER, LG DIBISCEGLIE, AM AF MANGIA, A MUSHAWAR, IK BERKENMEYER, LG DIBISCEGLIE, AM TI LIGASE CHAIN-REACTION FOR DETECTION OF MUTATIONS IN PRECORE REGION OF HBV GENOME SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. ABBOTT LABS,N CHICAGO,IL 60064. IRCCS CASA SOLLIEVO SOFFERENZA,SAN GIOVANNI ROTO,ITALY. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A307 EP A307 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600838 ER PT J AU MARRONE, A KLEINER, D MAHANEY, K CONJEEVERAM, H TADESCHI, V HOOFNAGLE, JH SALLIE, R AF MARRONE, A KLEINER, D MAHANEY, K CONJEEVERAM, H TADESCHI, V HOOFNAGLE, JH SALLIE, R TI THE SIGNIFICANCE OF HEPATIC HCV RNA - ANALYSIS BY SEMIQUANTITATIVE IN-SITU HYBRIDIZATION SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NCI,EXTRACELLULAR PATHOL LAB,BETHESDA,MD 20892. US FDA,CBER,BETHESDA,MD 20014. NR 0 TC 7 Z9 7 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 OCT PY 1994 VL 20 IS 4 BP A236 EP A236 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600555 ER PT J AU MORIMITSU, Y HSIA, CC KOJIRO, M TABOR, E AF MORIMITSU, Y HSIA, CC KOJIRO, M TABOR, E TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND ITS RECEPTOR IN THE DIFFERENT HISTOLOGIC GRADES OF HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. KURUME UNIV,SCH MED,DEPT PATHOL 1,KURUME,FUKUOKA 830,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A377 EP A377 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55601118 ER PT J AU MORIMITSU, Y KLEINER, DE HSIA, CC DIBISCEGLIE, AM TABOR, E AF MORIMITSU, Y KLEINER, DE HSIA, CC DIBISCEGLIE, AM TABOR, E TI TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) IN THE LIVER BEFORE AND AFTER INTERFERON-ALPHA (IFN-ALPHA) FOR CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A299 EP A299 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600807 ER PT J AU PARK, YM YOON, SK KIM, BS TABOR, E AF PARK, YM YOON, SK KIM, BS TABOR, E TI P53 MUTATIONS IN HEPATOCELLULAR CARCINOMAS (HCCS) FROM KOREA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CATHOLIC UNIV,COLL MED,KANGNAM ST MARYS HOSP,DEPT INTERNAL MED,SEOUL,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A384 EP A384 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55601146 ER PT J AU PARK, YM YOON, SK KIM, BS NOMURA, AMY STEMMERMANN, GM TABOR, E AF PARK, YM YOON, SK KIM, BS NOMURA, AMY STEMMERMANN, GM TABOR, E TI GENOMIC VARIATIONS IN PRECORE AND PROXIMAL CORE REGIONS OF HEPATITIS-B VIRUS (HBV) IN HEPATOCELLULAR-CARCINOMA (HCC) SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CATHOLIC UNIV,COLL MED,KANGNAM ST MARYS HOSP,DEPT INTERNAL MED,SEOUL,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A284 EP A284 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600748 ER PT J AU SALLIE, R KLEINER, D RICHARDSON, F CONJEEVARAM, H ZULLO, S MUTIMER, D HOOVER, S FOX, C HOOFNAGLE, JH AF SALLIE, R KLEINER, D RICHARDSON, F CONJEEVARAM, H ZULLO, S MUTIMER, D HOOVER, S FOX, C HOOFNAGLE, JH TI MECHANISMS OF FIAU INDUCED HEPATOTOXICITY SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NCI,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A209 EP A209 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600448 ER PT J AU SCHIRMACHER, P RADWAN, E ODENTHAL, M BURT, A VANDEWOUDE, GF DIENES, HP AF SCHIRMACHER, P RADWAN, E ODENTHAL, M BURT, A VANDEWOUDE, GF DIENES, HP TI HEPATOCYTE GROWTH FACTOR-SCATTER FACTOR AND C-MET EXPRESSION IN NORMAL AND CIRRHOTIC HUMAN LIVER SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV MAINZ,DEPT PATHOL,W-6500 MAINZ,GERMANY. UNIV NEWCASTLE UPON TYNE,INST PATHOL,NEWCASTLE TYNE NE1 7RU,TYNE & WEAR,ENGLAND. NCI,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A221 EP A221 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600495 ER PT J AU SHAKIL, AO CASEY, JL NIRO, GA DIBISCEGLIE, AM HOOFNAGLE, JH GERIN, JL AF SHAKIL, AO CASEY, JL NIRO, GA DIBISCEGLIE, AM HOOFNAGLE, JH GERIN, JL TI GENOTYPIC ANALYSIS OF HEPATITIS-D ISOLATES FROM PATIENTS WITH CHRONIC DELTA-HEPATITIS IN THE UNITED-STATES - DISEASE SEVERITY AND RESPONSE TO INTERFERON SO HEPATOLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,DMVI,ROCKVILLE,MD. NIH,LIVER DIS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A308 EP A308 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600842 ER PT J AU STUVER, S YUWEN, H OKAYAMA, A TACHIBANA, N TSUBOUCHI, H MUELLER, N TABOR, E AF STUVER, S YUWEN, H OKAYAMA, A TACHIBANA, N TSUBOUCHI, H MUELLER, N TABOR, E TI ASSOCIATION BETWEEN HEPATITIS-C VIRUS (HCV) INFECTION AND LIVER-CANCER MORTALITY WITHIN A JAPANESE POPULATION ENDEMIC FOR HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) INFECTION SO HEPATOLOGY LA English DT Meeting Abstract C1 OITA PREFECTURAL INST HLTH & ENVIRONM,OITA,JAPAN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. MIYAZAKI MED COLL,DEPT INTERNAL MED 2,MIYAZAKI 88916,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A285 EP A285 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600750 ER PT J AU SWAIN, MG MOGIAKOU, MA BERGASA, NV CHROUSOS, GP AF SWAIN, MG MOGIAKOU, MA BERGASA, NV CHROUSOS, GP TI FACILITATION OF ACTH AND CORTISOL RESPONSES TO CORTICOTROPIN-RELEASING HORMONE (CRH) IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS (PBC) SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LDS,BETHESDA,MD 20892. NICHHD,DEB,BETHESDA,MD 20892. NR 1 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A146 EP A146 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600196 ER PT J AU TSAREV, SA TSAREVA, TS EMERSON, SU GOVINDARAJAN, S PURCELL, RH AF TSAREV, SA TSAREVA, TS EMERSON, SU GOVINDARAJAN, S PURCELL, RH TI SUCCESSFUL PASSIVE AND ACTIVE IMMUNIZATION OF CYNOMOLGUS MONKEYS AGAINST HEPATITIS-E SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RANCHO LOS AMIGOS MED CTR,PATHOL LAB,DOWNEY,CA 90242. RANCHO LOS AMIGOS MED CTR,CLIN LAB,DOWNEY,CA 90242. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A203 EP A203 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600425 ER PT J AU TSUTSUI, H MATSUI, K NAKANISHI, K HIGASHINO, K OSWALD, IP INOUE, M AF TSUTSUI, H MATSUI, K NAKANISHI, K HIGASHINO, K OSWALD, IP INOUE, M TI FAS-FAS LIGAND INTERACTIONS UNDERLIE THE PATHOGENESIS OF ENDOTOXIN-INDUCED APOPTOTIC LIVER-INJURY SO HEPATOLOGY LA English DT Meeting Abstract C1 TONEYAMA INST TB RES,TONEYAMA,JAPAN. OSAKA CITY UNIV,SCH MED,DEPT BIOCHEM,OSAKA 545,JAPAN. HYOGO MED UNIV,DEPT INTERNAL MED 3,NISHINOMIYA,HYOGO 663,JAPAN. HYOGO MED UNIV,DEPT IMMUNOL & MED ZOOL,NISHINOMIYA,HYOGO 663,JAPAN. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RI OSWALD, Isabelle/A-8497-2013 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A183 EP A183 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600347 ER PT J AU WEISS, P ASHWELL, G AF WEISS, P ASHWELL, G TI ESTIMATION OF SERUM ASIALOGLYCOPROTEINS LEVEL BY HYDROLYSIS AND ANION-EXCHANGE CHROMATOGRAPHY WITH PULSED AMPEROMETRIC DETECTION OF SIALIC-ACID AND GALACTOSE SO HEPATOLOGY LA English DT Meeting Abstract C1 TEL AVIV UNIV,CHAIM SHEBA MED CTR,DEPT MED B,TEL HASHOMER,ISRAEL. TEL AVIV UNIV,CHAIM SHEBA MED CTR,LIVER UNIT,TEL HASHOMER,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,TEL AVIV,ISRAEL. NIDDKD BIOCHEM & METAB LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A413 EP A413 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55601262 ER PT J AU YURDAYDIN, C ENGLER, H WALSH, TJ HA, JH JONES, EA BASILE, AS AF YURDAYDIN, C ENGLER, H WALSH, TJ HA, JH JONES, EA BASILE, AS TI BENZODIAZEPINE RECEPTOR LIGANDS (BRL) ARE SYNTHESIZED DE-NOVO IN THE BRAIN SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. NCI,PAEDIAT BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600051 ER PT J AU YUWEN, H KAZACHKOV, Y MORIMITSU, Y TABOR, E AF YUWEN, H KAZACHKOV, Y MORIMITSU, Y TABOR, E TI WILD-TYPE-P53 PRODUCED BY RECOMBINANT VACCINIA VIRUS FOR THE STUDY OF ITS FUNCTION IN HEPATOCELLULAR-CARCINOMA CELL-LINES SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A286 EP A286 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600753 ER PT J AU WITKOP, B BROSSI, A AF WITKOP, B BROSSI, A TI BAN,YOSHI (1921-1994), A BUILDER OF BRIDGES SO HETEROCYCLES LA English DT Item About an Individual RP WITKOP, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD OCT 1 PY 1994 VL 38 IS 10 BP R1 EP R2 PG 2 WC Chemistry, Organic SC Chemistry GA PM485 UT WOS:A1994PM48500001 ER PT J AU BRODSKY, RA JANE, SM VANIN, EF MITSUYA, H PETERS, TR SHIMADA, T MEDOF, ME NIENHUIS, AW AF BRODSKY, RA JANE, SM VANIN, EF MITSUYA, H PETERS, TR SHIMADA, T MEDOF, ME NIENHUIS, AW TI PURIFIED GPI-ANCHORED CD4DAF AS A RECEPTOR FOR HIV-MEDIATED GENE-TRANSFER SO HUMAN GENE THERAPY LA English DT Article ID DECAY-ACCELERATING FACTOR; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; IMMUNODEFICIENCY-VIRUS INFECTION; SOLUBLE CD4; CELLS; PROTEIN; VECTOR; INHIBITION; LYMPHOCYTES; ACTIVATION AB CD4 is the major cellular receptor for the human immunodeficiency virus (HIV). A hybrid gene encoding the extracellular domains of CD4, linked to the sequence encoding the membrane attachment region of the glycosylphosphatidylinositol (GPI)-anchored protein decay accelerating factor (DAF) was stably transfected into HeLa cells. The resultant cell line (T4HD) expressed GPI-anchored CD4DAF at high levels and was susceptible to gene transfer with a recombinant HIV vector. In an effort to expand the spectrum of cells susceptible to HIV gene transfer, CD4DAF was released from the surface of the T4HD cell line by detergent lysis, purified by immunoaffinity chromatography, and reincorporated into native HeLa cells. Incorporation occurred via the GPI anchor as evidenced by cleavage with phosphatidylinositol-specific phospholipase C. More than 95% of the CD4DAF-treated HeLa cells were CD4-positive by flow cytometry, and kinetic analysis demonstrated that over 75% of the fusion protein remained anchored to the cell membrane after 90 min at 37 degrees C. The purified protein retained its ability to bind the envelope protein of HIV. When incorporated, it bound fluorescein isothiocyanate (FITC)-conjugated gp120, and in its soluble form blocked transduction of CD4-positive cells incubated with an HIV-derived vector containing the Neo(R) gene. In contrast to the T4HD cells, exposure of CD4DAF-treated cells to the Neo(R) HIV vector yielded only transient neomycin-resistant colonies. These results suggest that endogenous synthesis of the CD4 molecule may be necessary for successful HIV genomic integration. C1 ST JUDE CHILDRENS RES HOSP, DIV EXPTL HEMATOL, MEMPHIS, TN 38101 USA. JOHNS HOPKINS UNIV, CTR ONCOL, BALTIMORE, MD 21205 USA. GENET THERAPY INC, GAITHERSBURG, MD 20798 USA. NCI, BETHESDA, MD 20892 USA. NIPPON MED COLL, DEPT BIOCHEM & MOLEC BIOL, TOKYO 113, JAPAN. CASE WESTERN RESERVE UNIV, INST PATHOL, CLEVELAND, OH 44106 USA. RI Jane, Stephen/D-6659-2011 NR 36 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 1994 VL 5 IS 10 BP 1231 EP 1239 DI 10.1089/hum.1994.5.10-1231 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PN314 UT WOS:A1994PN31400006 PM 7531502 ER PT J AU ROME, JJ SHAYANI, V NEWMAN, KD FARRELL, S LEE, SW VIRMANI, R DICHEK, DA AF ROME, JJ SHAYANI, V NEWMAN, KD FARRELL, S LEE, SW VIRMANI, R DICHEK, DA TI ADENOVIRAL VECTOR-MEDIATED GENE-TRANSFER INTO SHEEP ARTERIES USING A DOUBLE-BALLOON CATHETER SO HUMAN GENE THERAPY LA English DT Article ID CORONARY-ARTERIES; EXPRESSION INVIVO; IN-VIVO; WALL; CELLS AB The potential for catheter-based in vivo delivery of genetic material to the arterial wall is incompletely explored. We evaluated the level of recombinant protein production as well as the anatomic distribution and duration of gene expression following adenoviral vector-mediated gene transfer into sheep arteries via a double balloon catheter. Catheters were positioned in the carotid or femoral arteries of 20 sheep via a combined percutaneous and surgical approach, and virions infused over a 30-min period. Three days later, recombinant gene expression was identified in approximately 30% (range 0-80%) of the luminal endothelial cells within the targeted area of the artery. Persistent recombinant protein expression was identified histochemically for up to 4 weeks, although the number of positive cells decreased steadily. High levels of both beta-galactosidase (beta-Gal) activity and protein (mean 20 mU and 44 ng per vessel) were measured in vessel extracts 3 days after gene transfer, again decreasing significantly over a 4-week period. Transgene expression was limited almost entirely to the intima and adventitia; adventitial gene transfer occurred virtually exclusively along the vasa vasorum. In comparison to previous studies of catheter-based gene transfer, adenoviral vectors delivered by double balloon catheter resulted in a particularly high efficiency of endothelial cell gene transfer. The efficiency and amount of recombinant gene expression achieved in this study suggest that catheter-based gene delivery may eventually be applicable to the treatment of focal human arterial disease. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT CARDIOL,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT SURG,WASHINGTON,DC 20010. ARMED FORCES INST PATHOL,CARDIOVASC SECT,WASHINGTON,DC 20307. NR 21 TC 39 Z9 39 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 1994 VL 5 IS 10 BP 1249 EP 1258 DI 10.1089/hum.1994.5.10-1249 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PN314 UT WOS:A1994PN31400008 PM 7849097 ER PT J AU SHAW, S AF SHAW, S TI LEUKOCYTE DIFFERENTIATION ANTIGENS HOW TO KEEP UP WITH THE LITANY OF CD ANTIGENS SO HUMAN IMMUNOLOGY LA English DT Editorial Material RP SHAW, S (reprint author), NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 1994 VL 41 IS 2 BP 103 EP 104 DI 10.1016/0198-8859(94)90001-9 PG 2 WC Immunology SC Immunology GA PN485 UT WOS:A1994PN48500001 PM 7860353 ER PT J AU NAVARROROMAN, L CORBIN, DOC KATZ, D CALLENDER, DPE PRUSSIA, PR GARRIQUES, S FRASER, HS JAFFE, ES ROMAN, GC AF NAVARROROMAN, L CORBIN, DOC KATZ, D CALLENDER, DPE PRUSSIA, PR GARRIQUES, S FRASER, HS JAFFE, ES ROMAN, GC TI HUMAN T-LYMPHOTROPIC VIRUS TYPE-I DNA IN SPINAL-CORD OF TROPICAL SPASTIC PARAPARESIS WITH CONCOMITANT HUMAN T-LYMPHOTROPIC VIRUS TYPE-I NEGATIVE HODGKINS-DISEASE SO HUMAN PATHOLOGY LA English DT Note DE HODGKINS DISEASE; HUMAN T-LYMPHOTROPIC VIRUS TYPE I; LYMPHOMA; MYELOPATHY; RETROVIRUS INFECTIONS; POLYMERASE CHAIN REACTION; TROPICAL SPASTIC PARAPARESIS ID CELL LEUKEMIA-LYMPHOMA; POLYMERASE CHAIN-REACTION; REED-STERNBERG CELLS; HTLV-I; PROVIRAL DNA; MYELOPATHY; REPLICATION; ANTIBODIES; SEQUENCES; SERUM AB We studied a 58-year-old black woman from Barbados who simultaneously developed myelopathy and lymphoma with human T-lymphotropic virus type I (HTLV-I) antibodies in serum and cerebrospinal fluid and died 3 years after onset. Neuropathological examination showed typical tropical spastic paraparesis (TSP). The polymerase chain reaction (PCR) demolzstrated defective proviral genome retaining the HTLV-I pX and env regions in thoracic spinal cord, the level most severely affected. Defective HTLV-I in the nervous system retaining the pX region may be relevant to pathogenesis because circulating CD8+ cytotoxic lymphocytes specific for HTLV-I pX occur in HTLV-I myelopathy. This patient's lymph node biopsy specimen was consistent with Hodgkin's disease (HD), nodular sclerosis subtype, of B-cell origin. The PCR in the paraffin-embedded lymph node involved by HC, failed to amplify HTLV-I poviral sequences. Complete HTLV-I proviral amplification was obtained in paraffin-embedded lymph nodes from positive controls (adult T-cell leukemia). To our knowledge the association of TSP and HD has not been reported previously. Despite claims that HD may be associated with HTLV-I, we demonstrated absence of HTLV-I-infected T cells in the lymphoid infiltrate of HD in this case, positive HTLV-I serology notwithstanding. C1 QUEEN ELIZABETH HOSP,BRIDGETOWN,BARBADOS. NCI,HEMATOPATHOL LAB,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NIH,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. RP NAVARROROMAN, L (reprint author), UNIV TEXAS,HLTH SCI CTR,SCH MED,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1994 VL 25 IS 10 BP 1101 EP 1106 DI 10.1016/0046-8177(94)90072-8 PG 6 WC Pathology SC Pathology GA PL449 UT WOS:A1994PL44900018 PM 7927317 ER PT J AU BROWN, P AF BROWN, P TI VERTICAL TRANSMISSION OF PRION DISEASE SO HUMAN REPRODUCTION LA English DT Note ID CREUTZFELDT-JAKOB DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY RP BROWN, P (reprint author), NIH,BLDG 36,ROOM 5B21,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 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 OCT PY 1994 VL 9 IS 10 BP 1796 EP 1797 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PN837 UT WOS:A1994PN83700005 ER PT J AU DORFMAN, N DIETZSCHOLD, B KAJIYAMA, W FU, ZF KOPROWSKI, H NOTKINS, AL AF DORFMAN, N DIETZSCHOLD, B KAJIYAMA, W FU, ZF KOPROWSKI, H NOTKINS, AL TI DEVELOPMENT OF HUMAN MONOCLONAL-ANTIBODIES TO RABIES SO HYBRIDOMA LA English DT Article ID VIRUS-NEUTRALIZING EPITOPE; QUANTITATION; GLYCOPROTEIN; VACCINE; CELLS AB A total of nine human monoclonal antibodies (MAbs) to rabies virus were generated from peripheral B lymphocytes of subjects immunized with human diploid cell rabies vaccine by somatic cell hybridization. The MAbs were analyzed for their antigen-binding specificities using ELISA, Western blot, and immunoprecipitation assays. The different assays made it possible to identify MAbs directed to the surface glycoprotein, nucleoprotein, nominal phosphoprotein, and matrix protein. One of the MAbs that recognized the surface glycoprotein neutralized rabies virus. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,CTR NEUROVIROL,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. FU NIAID NIH HHS [AI-09706] NR 24 TC 7 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 1994 VL 13 IS 5 BP 397 EP 402 DI 10.1089/hyb.1994.13.397 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA PP892 UT WOS:A1994PP89200008 PM 7860096 ER PT J AU WONG, PMC HAN, XD RUSCETTI, FW CHUNG, SW AF WONG, PMC HAN, XD RUSCETTI, FW CHUNG, SW TI IMMORTALIZED HEMATOPOIETIC-CELLS WITH STEM-CELL PROPERTIES SO IMMUNITY LA English DT Article ID GROWTH-FACTOR-BETA; CFU-S CELL; HEMATOPOIETIC STEM; BONE-MARROW; W/WV MICE; TERATOCARCINOMA CELLS; TRANSCRIPTION FACTOR; INTERLEUKIN-3 GENE; SELF-RENEWAL; V-ABL AB We have established a hemopoietic cell line, BL3, that possesses a rearranged retroviral genome, which we used as a genetic tag for their engraftment into lethally irradiated mice. Analysis of recipients up to 7 months after engraftment indicates that the marker was present in differentiated cells of various hemopoietic organs, in colony-forming cells, pre-CFU-S-forming cells, and in organs of secondary recipients from bone marrow cells of primary recipients. BL3 cells are Thy-1(+), Sca-1(+), B220(-), Mac-1(-), and Gr1(-). They express GATA-1 and are able to develop ''cobblestones'' with stromal cells. They do not express and respond to several hemopoietic growth factors known to facilitate marrow recovery. However, they are negatively regulated by TGF beta and can be stimulated by mitogenstimulated spleen cell-conditioned medium. We conclude that BL3 cells possess properties of hemopoietic stem cells, including their capability to contribute to long-term repopulation. C1 TEMPLE UNIV,FELS INST CANC RES & MOLEC BIOL,DEPT MICROBIOL,PHILADELPHIA,PA 19140. TEMPLE UNIV,FELS INST CANC RES & MOLEC BIOL,DEPT IMMUNOL,PHILADELPHIA,PA 19140. SUNY,MORSE INST MOLEC GENET,DEPT MICROBIOL & IMMUNOL,BROOKLYN,NY 11203. NCI,LEUKOCYTE BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP WONG, PMC (reprint author), TEMPLE UNIV,FELS INST CANC RES & MOLEC BIOL,DEPT BIOCHEM,3307 N BROAD ST,PHILADELPHIA,PA 19140, USA. FU NCI NIH HHS [5P30CA12227]; NHLBI NIH HHS [HL46547]; NIDDK NIH HHS [DK41298] NR 67 TC 18 Z9 18 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1994 VL 1 IS 7 BP 571 EP 583 DI 10.1016/1074-7613(94)90047-7 PG 13 WC Immunology SC Immunology GA PN127 UT WOS:A1994PN12700006 PM 7600286 ER PT J AU SEOW, HF YOSHIMURA, T WOOD, PR COLDITZ, IG AF SEOW, HF YOSHIMURA, T WOOD, PR COLDITZ, IG TI CLONING, SEQUENCING, EXPRESSION AND INFLAMMATORY ACTIVITY IN SKIN OF OVINE INTERLEUKIN-8 SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE EOSINOPHILS; INFLAMMATION; LYMPHOCYTES; NEUTROPHILS; OVINE IL-8; SHEEP ID ATTRACTANT ACTIVATION PROTEIN-1; NEUTROPHIL CHEMOTACTIC FACTOR; MOLECULAR-CLONING; ESCHERICHIA-COLI; LYMPHOCYTES-T; MESSENGER-RNA; CDNA CLONING; FACTOR MDNCF; GUINEA-PIG; INVIVO AB Ovine IL-8 (oIL-8) cDNA was obtained by probing a spleen cell cDNA library with human IL-8 (hIL-8) cDNA. The oIL-8 cDNA was 1434 base pairs long with a single open reading frame encoding a 101 amino acid precursor protein of relative molecular mass 11 268. The inferred amino acid sequence has 78, 82, 84 and 67% similarity with human, rabbit, porcine and guinea-pig IL-8, respectively. By analogy with the most prevalent form of hIL-8, a 72 amino acid form of oIL-8 was expressed as a fusion protein containing glutathione-S-transferase and purified by affinity chromatography on a glutathione-Sepharose column yielding 8 mg IL-8/L broth culture. The fusion protein lacked chemotactic activity for ovine neutrophils, whereas the 72 amino acid form of oIL-8 was equipotent with rhIL-8. At 6 and 24 h after intradermal injection of 10(-9) mol oIL-8, there was intense accumulation of neutrophils, and very mild accumulation of eosinophils, CD5, CD4 and T19 (a gamma delta TCR subset) cells but not CD8 cells. The availability of roIL-8 and its cDNA probes will permit the role of this important member of the IL-8 family of chemotactic cytokines to be determined in inflammatory diseases of sheep. C1 CSIRO,PASTORAL RES LAB,ARMIDALE,NSW 2350,AUSTRALIA. CSIRO,DIV ANIM HLTH,PARKVILLE,VIC,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. RI Colditz, Ian/A-1289-2008; OI Colditz, Ian/0000-0001-9497-5148; Seow, Heng Fong/0000-0002-2189-327X NR 30 TC 33 Z9 34 U1 0 U2 2 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 1994 VL 72 IS 5 BP 398 EP 405 DI 10.1038/icb.1994.59 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PU531 UT WOS:A1994PU53100006 PM 7835984 ER PT J AU KOHLER, H MULLER, S NARA, PL AF KOHLER, H MULLER, S NARA, PL TI DECEPTIVE IMPRINTING IN THE IMMUNE-RESPONSE AGAINST HIV-1 SO IMMUNOLOGY TODAY LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; UNRELATED ALLOANTIGENS; DOMINANT IMMUNIZATION; ANTIGENIC VARIATION; KAPPA-LIGHT; AIDS; ANTIBODIES; INFECTION; GP120 AB The clonal profile of anti-HIV-1 antibodies is established at the time of infection as part of a vigorous immune response against HIV-1, and remains stable during the infection process. This bias towards antibodies specific for the initially, infecting clonal virus population, termed imprinting, is inappropriate for attempts of the infected host to control viral variants that subsequently emerge. Here, Heinz Kohler, Sybille Muller and Peter Nara argue that immunodominant epitopes on viral variants or recombinant proteins are selected that induce and maintain this deceptive state, and thereby remain unrecognized through, a functional and crossreactive hole in the B-cell repertoire. C1 NCI,VIRUS BIOL SECT,TUMOR CELL BIOL LAB,FREDERICK,MD 21702. RP KOHLER, H (reprint author), UNIV KENTUCKY,MED CTR,LUCILLE P MARKEY CANC CTR,COMBS BLDG,800 ROSE ST,LEXINGTON,KY 40536, USA. NR 37 TC 60 Z9 60 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 OCT PY 1994 VL 15 IS 10 BP 475 EP 478 DI 10.1016/0167-5699(94)90192-9 PG 4 WC Immunology SC Immunology GA PK126 UT WOS:A1994PK12600006 PM 7945772 ER PT J AU BORNSTEIN, MH TAMISLEMONDA, CS AF BORNSTEIN, MH TAMISLEMONDA, CS TI ANTECEDENTS OF INFORMATION-PROCESSING SKILLS IN INFANTS - HABITUATION, NOVELTY RESPONSIVENESS, AND CROSS-MODAL TRANSFER SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE HABITUATION; NOVELTY RESPONSIVENESS; CROSS-MODAL TRANSFER; PARENTING INTERACTIONS; PREDICTION ID MOTHER-INFANT; COGNITIVE COMPETENCE; VISUAL HABITUATION; CONTINUITY; PREDICTORS; STABILITY; PERFORMANCE; STATES; CHILD; LIFE AB Three skills which characterize cognitive functioning in human infants in the middle of the first year of life-habituation, novelty responsiveness, and cross-modal transfer-predict mental ability in later childhood. Antecedents of each skill at 5 months postnatal were examined in a shortterm prospective longitudinal study of infant ability and maternal intelligence and interaction style. Infant perceptuocognitive performance at 2 months, maternal intelligence, and maternal responsiveness at 5 months relate to the expression of the three infant cognitive skills, but in different ways. Variation in infant information-processing abilities can be explained by specific child and maternal factors that are evident soon after birth. C1 NYU,NEW YORK,NY. RP BORNSTEIN, MH (reprint author), NICHHD,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 54 TC 19 Z9 19 U1 1 U2 2 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD OCT-DEC PY 1994 VL 17 IS 4 BP 371 EP 380 DI 10.1016/0163-6383(94)90029-9 PG 10 WC Psychology, Developmental SC Psychology GA QN153 UT WOS:A1994QN15300003 ER PT J AU GRANT, CCR MESSER, RJ CIEPLAK, W AF GRANT, CCR MESSER, RJ CIEPLAK, W TI ROLE OF TRYPSIN-LIKE CLEAVAGE AT ARGININE-192 IN THE ENZYMATIC AND CYTOTONIC ACTIVITIES OF ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN SO INFECTION AND IMMUNITY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; ADENOSINE-DIPHOSPHATE-RIBOSYLATION; SITE-SPECIFIC MUTAGENESIS; CHOLERA-TOXIN; VIBRIO-CHOLERAE; PSEUDOMONAS EXOTOXIN; ADENYLATE-CYCLASE; NUCLEOTIDE BINDING; CELLULAR PROTEASE; BREFELDIN-A AB Previous studies of cholera toxin and Escherichia coli heat-labile enterotoxin have suggested that proteolytic cleavage plays an important role in the expression of ADP-ribosyltransferase activity and toxicity. Specifically, several studies have implicated a trypsin-like cleavage at arginine 192, which lies within an exposed region subtended by a disulfide bond in the intact A subunit, in toxicity. To investigate the role of this modification in the enzymatic and cytotonic properties of heat-labile enterotoxin, the response of purified, recombinant A subunit to tryptic activation and the effect of substituting arginine 192 with glycine on the activities of the holotoxin were examined. The recombinant A subunit of heat-labile enterotoxin exhibited significant levels of ADP-ribosyltransferase activity that were only nominally increased (approximately twofold) by prior limited trypsinolysis. The enzymatic activity also did not appear to be affected by auto-ADP-ribosylation that occurs during the high-level synthesis of the recombinant A subunit in E. coli. A mutant form of the holotoxin containing the arginine 192-to-glycine substitution exhibited levels of cytotonic activity for CHO cells that were similar to that of the untreated, wild-type holotoxin but exhibited a marked delay in the ability to increase intracellular levels of cyclic AMP in Caco-2 cells. The results indicate that trypsin-like cleavage of the A subunit of E. coli heat-labile enterotoxin at arginine 192 is not requisite to the expression of enzymatic activity by the A subunit and further reveal that this modification, although it enhances the biological and enzymatic activities of the toxin, is not absolutely required for the enterotoxin to elicit cytotonic effects. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. NR 49 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1994 VL 62 IS 10 BP 4270 EP 4278 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH298 UT WOS:A1994PH29800024 PM 7927684 ER PT J AU PARTA, M CHANG, Y RULONG, S PINTODASILVA, P KWONCHUNG, KJ AF PARTA, M CHANG, Y RULONG, S PINTODASILVA, P KWONCHUNG, KJ TI HYP1, A HYDROPHOBIN GENE FROM ASPERGILLUS-FUMIGATUS, COMPLEMENTS THE RODLETLESS PHENOTYPE IN ASPERGILLUS-NIDULANS SO INFECTION AND IMMUNITY LA English DT Article ID SCHIZOPHYLLUM-COMMUNE; CHEMICAL-COMPOSITION; RHIZOPUS-ORYZAE; TRANSFORMATION; FUNGI; ULTRASTRUCTURE; RESISTANCE; SURFACE; CONIDIA; INVITRO AB Aspergillus fumigatus produces conidia that are highly dispersable and resistant to degradation. We have sought to analyze these properties by studying the rodlets which form the outer spore coat protein. Degenerate primers based on hydrophobins in other fungi were applied to genomic DNA from A. fumigatus in PCR. A product of this reaction with similarity to an Aspergillus nidulans gene as judged by Southern hybridization was chosen for further study. Cloning and sequencing revealed a gene with two introns which encodes a protein of 159 amino acids. Structural characteristics consistent with those of other fungal hydrophobin genes, especially conserved cysteine residues, are present. The expression of the gene is limited to the developmental stages in which maturing conidiophores are present. This A. fumigatus gene, HYP1, was used to transform a mutant strain of A. nidulans that lacks rodlets. Transformants,vith a single copy of HYP1 expressed a rodlet layer on their conidia as observed by freeze-fracture electron microscopy. C1 NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES FACIL, MATH BIOL LAB, MEMBRANE BIOL SECT, FREDERICK, MD USA. NR 24 TC 52 Z9 55 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1994 VL 62 IS 10 BP 4389 EP 4395 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH298 UT WOS:A1994PH29800040 PM 7927700 ER PT J AU SZU, SC TAYLOR, DN TROFA, AC CLEMENTS, JD SHILOACH, J SADOFF, JC BRYLA, DA ROBBINS, JB AF SZU, SC TAYLOR, DN TROFA, AC CLEMENTS, JD SHILOACH, J SADOFF, JC BRYLA, DA ROBBINS, JB TI LABORATORY AND PRELIMINARY CLINICAL CHARACTERIZATION OF VI CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; TYPHOID-FEVER; SALMONELLA-TYPHI; ESCHERICHIA-COLI; CHOLERA-TOXIN; BONE-MARROW; CHILDREN; CULTURES; IMMUNOGENICITY; PREVENTION AB To improve its immunogenicity for children and adults and to make it suitable for routine immunization of infants against typhoid fever, the capsular polysaccharide of Salmonella typhi (Vi) was bound to the B subunit of the heat-labile toxin (LT-B) of Escherichia coli or the recombinant exoprotein ii (rEPA) of Pseudomonas aeruginosa. The conjugates elicited higher levels of antibodies (micrograms per milliliter of serum) in mice and in guinea pigs than did Vi and, unlike Vi alone, elicited booster antibody responses in both species. In adult volunteers, Vi-LT-B and Vi-rEPA respectively, elicited higher levels of antibodies than Vi alone after the first injection (4.74 versus 1.77 and 4.91 versus 1.77; P < 0.005) and 26 weeks later (2.32 and 2.69 versus 0.54; P < 0.04); a second injection of the conjugates did not elicit a booster response of Vi antibodies. None of the 51 vaccinees had fever or significant local reactions. Vi-rEPA elicited slightly higher levels of Vi antibodies than did Vi-LT-B at II intervals after injection, but these differences were not significant. Each conjugate elicited antibodies to its carrier protein. The antibody responses elicited in adults by Vi bound to LT-B and rEPA are similar to those of other polysaccharide-protein conjugates. These conjugates promise to be an improved Vi vaccine. Studies of Vi conjugates with adults and infants in areas where typhoid is endemic are planned. C1 NIDDKD,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. TULANE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,NEW ORLEANS,LA 70112. RP SZU, SC (reprint author), NICHHD,BLDG 6,RM 145,BETHESDA,MD 20892, USA. NR 47 TC 80 Z9 82 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1994 VL 62 IS 10 BP 4440 EP 4444 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH298 UT WOS:A1994PH29800047 PM 7927707 ER PT J AU VOGEL, SN WAX, JS PERERA, PY PADLAN, C POTTER, M MOCK, BA AF VOGEL, SN WAX, JS PERERA, PY PADLAN, C POTTER, M MOCK, BA TI CONSTRUCTION OF A BALB/C CONGENIC MOUSE, C.C3H-LPS(D), THAT EXPRESSES THE LPS(D) ALLELE - ANALYSIS OF CHROMOSOME-4 MARKERS SURROUNDING THE LPS GENE SO INFECTION AND IMMUNITY LA English DT Article ID MICE; LIPOPOLYSACCHARIDE; MACROPHAGES; PLASMACYTOMAGENESIS; ENDOTOXIN; CLONES; FAMILY; MAP; IFA AB Development of a congenic BALB/c mouse strain that contains a segment of chromosome 4 including the Lps(d) allele of the lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ strain is presented. On the basis of LPS-induced spleen cell mitogenesis, macrophage tumor necrosis factor secretion, and tyrosine-phosphorylation in vitro and lethality in galactosamine-sensitized mice in vivo, the C.C3H-Lps(d) strain provides a model of LPS hyporesponsiveness that is comparable to that of the parental C3H/HeJ strain. Analysis of markers in this region indicates that length of the donor fragment is similar to 5.5 centimorgans. Thus, the C.C3H-Lps(d) strain provides an important genetic tool for analysis of markers in this region and for examining functional effects of Lps(d) expression on the BALB/c background. C1 ORGANON TECHN,ROCKVILLE,MD 20850. NCI,GENET LAB,BETHESDA,MD 20892. RP VOGEL, SN (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814, USA. FU NCI NIH HHS [N01-CB-21075]; NIAID NIH HHS [AI-18797]; PHS HHS [R07338] NR 34 TC 41 Z9 41 U1 1 U2 2 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 OCT PY 1994 VL 62 IS 10 BP 4454 EP 4459 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH298 UT WOS:A1994PH29800049 PM 7927709 ER PT J AU KOLENBRANDER, PE ANDERSEN, RN GANESHKUMAR, N AF KOLENBRANDER, PE ANDERSEN, RN GANESHKUMAR, N TI NUCLEOTIDE-SEQUENCE OF THE STREPTOCOCCUS-GORDONII PK488 COAGGREGATION ADHESIN GENE, SCAA, AND ATP-BINDING CASSETTE SO INFECTION AND IMMUNITY LA English DT Article ID ACTINOMYCES-NAESLUNDII PK606; DEPENDENT TRANSPORT-SYSTEMS; CELL-SURFACE POLYPEPTIDE; SALIVARY-AGGLUTININ; ESCHERICHIA-COLI; PROTEIN SSAB; ANTIGEN-I/II; SANGUIS 12; BACTERIA; CLONING AB Human oral viridans group streptococci that coaggregate with Actinomyces naeslundii PK606 express surface proteins related to ScaA, the coaggregation-mediating adhesin of Streptococcus gordonii PK488 (R. N, Andersen, N, Ganeshkumar, and P. E, Kolenbrander, Infect. Immun. 61:981-987, 1993). The nucleotide sequence of the 6,125-bp EcoRI insert of pRA1, containing scaA, the gene encoding ScaA, was determined. Six open reading frames (ORFs) were identified. The orientation of four ORFs, two upstream (ORF 1 and ORF 2) and one downstream (ORF 4) of scaA (ORF 3), indicated transcription in one direction, whereas ORF 5 and ORF 6 were transcribed divergently. Computer analysis of the deduced amino acid sequences identified a consensus binding site for ATP (GxxGxGKS) in the putative 28,054-Da protein encoded by ORF 1. ORF 2 potentially encoded a hydrophobic protein of 29,705 Da with six potential membrane-spanning regions. ScaA was 310 amino acids, 34,787 Da, and contained the lipoprotein consensus sequence LxxC, also reported for the ScaA-related proteins SsaB, FimA, and PsaA from Streptococcus sanguis 12, Streptococcus parasanguis FW213, and Streptococcus pneumoniae R36A, respectively. ORF 4 potentially encoded a 163-amino-acid protein of 17,912 Da, which was nearly identical to the downstream adjacent gene products of ssaB, fim-A, and psaA. No significant homology with other proteins was found with the putative ORF 5 gene product, a 229-amino-acid protein of 25,107 Da. ORF 6 was incomplete and encoded a protein larger than 564 amino acids. This putative protein had a consensus Zn2+ binding motif, HExxH, found among bacterial thermolysins and mammalian neutral endopeptidases and was 40% identical to a homologous 210-amino-acid region of human enkephalinase. The genetic organization of ORFs 1, 2, and 3 was similar to those of the bacterial periplasmic-binding protein-dependent transport systems of gram-negative bacteria and binding-lipoprotein-dependent transport systems of gram-positive bacteria, and these genes appeared to encode ABC (ATP-binding cassette) proteins. This report describes a cell-to-cell adherence function associated with an ATP-binding cassette. RP KOLENBRANDER, PE (reprint author), NIDR,MICROBIAL ECOL LAB,BLDG 30,ROOM 310,BETHESDA,MD 20892, USA. NR 67 TC 91 Z9 98 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1994 VL 62 IS 10 BP 4469 EP 4480 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH298 UT WOS:A1994PH29800051 PM 7927711 ER PT J AU LUJAN, HD BYRD, LG MOWATT, MR NASH, TE AF LUJAN, HD BYRD, LG MOWATT, MR NASH, TE TI SERUM COHN FRACTION IV-1 SUPPORTS THE GROWTH OF GIARDIA-LAMBLIA IN-VITRO SO INFECTION AND IMMUNITY LA English DT Note ID TERMINAL SEQUENCE; SURFACE-PROTEINS; AXENIC CULTURE; HUMAN-PLASMA; FACTOR-II; ERYTHROTROPIN; CULTIVATION; PEPTIDES; ORIGIN; BILE AB Bovine serum Cohn fractions were substituted for whole bovine serum in TYI-S-33 medium. Only fraction IV-1 supported attachment, cysteine uptake, and growth of Giardia lamblia. Among the mammalian sources tested, only goat and horse fractions showed activities comparable to that of the bovine faction. Agglutinating immunoglobulins were identified as deleterious agents to human, rat, rabbit, and dog fractions. RP LUJAN, HD (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 12 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1994 VL 62 IS 10 BP 4664 EP 4666 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH298 UT WOS:A1994PH29800081 PM 7927737 ER PT J AU HENDERSON, DK AF HENDERSON, DK TI HIV SCREENING FOR HEALTH-CARE PROVIDERS - CAN WE PROVIDE SENSE AND SENSIBILITY WITHOUT PRIDE OR PREJUDICE SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID DENTAL PRACTICE; LOOK-BACK; TRANSMISSION; SURGEON; DENTISTS; ABSENCE; RISK; AIDS; HBV RP HENDERSON, DK (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,CTR CLIN,BLDG 10,ROOM 2C 146,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 1994 VL 15 IS 10 BP 631 EP 634 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA PK599 UT WOS:A1994PK59900001 PM 7844333 ER PT J AU ROIZMAN, B JOKLIK, W FIELDS, B MOSS, B AF ROIZMAN, B JOKLIK, W FIELDS, B MOSS, B TI THE DESTRUCTION OF SMALLPOX VIRUS STOCKS IN NATIONAL REPOSITORIES - A GRAVE MISTAKE AND A BAD PRECEDENT SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Editorial Material C1 DUKE UNIV,DEPT MICROBIOL,DURHAM,NC. HARVARD UNIV,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NIH,VIRAL DIS LAB,BETHESDA,MD 20892. RP ROIZMAN, B (reprint author), UNIV CHICAGO,MARJORIE B KOVLER VIRAL ONCOL LABS,910 E 58TH ST,CHICAGO,IL 60637, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD OCT PY 1994 VL 3 IS 5 BP 215 EP 217 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PV665 UT WOS:A1994PV66500001 PM 7866654 ER PT J AU SHIMOJO, N KATSUKI, T COLIGAN, JE NISHIMURA, Y SASAZUKI, T TSUNOO, H SAKAMAKI, T KOHNO, Y NIIMI, H AF SHIMOJO, N KATSUKI, T COLIGAN, JE NISHIMURA, Y SASAZUKI, T TSUNOO, H SAKAMAKI, T KOHNO, Y NIIMI, H TI IDENTIFICATION OF THE DISEASE-RELATED T-CELL EPITOPE OF OVALBUMIN AND EPITOPE-TARGETED T-CELL INACTIVATION IN EGG ALLERGY SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE OVALBUMIN; T CELL LINE; EPITOPE; ANALOG PEPTIDE; CYTOKINE; ALLERGY, HEN EGG ID MULTIPLE-SCLEROSIS PATIENTS; MYELIN BASIC-PROTEIN; LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; LYMPHOKINE PRODUCTION; PEPTIDE; RECOGNITION; RESTRICTION; ANTIGEN; IGE AB An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with hen egg allergy. The TCL was CD4+, expressed alpha beta T cell receptor, and recognized OVA presented by HLA-DR10. Based on the response of the TCL to synthetic OVA peptides, it was found that the TCL recognized OVA 323-339, which is a major T cell epitope presented by murine I-A(d). The TCL secreted high levels of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth and chemotactic factor for eosinophils, it is possible that these OVA 323-339-specific T cells can contribute to human egg allergy. To our knowledge, this is the first demonstration of food allergen-specific TCL establishment and identification of a T cell epitope possibly I-elated to the allergic reaction to food antigens. An analog peptide of the OVA 323-339 which is known to strongly bind to I-A(d) partially inhibited the response of the TCL to OVA 323-339 presented by HLA-DR10, raising the possibility of peptide-based immunotherapy of food allergy. C1 KYUSHU UNIV,INST BIOREGULAT,DEPT MED GENET,FUKUOKA,JAPAN. MEIJI INST HLTH SCI,ODAWARA,JAPAN. SAKURA NATL HOSP,SAKURA,CHIBA,JAPAN. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP SHIMOJO, N (reprint author), CHIBA UNIV,SCH MED,DEPT PEDIAT,CHUO KU,1-8-1 INOHANA,CHIBA 260,JAPAN. NR 30 TC 33 Z9 34 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD OCT PY 1994 VL 105 IS 2 BP 155 EP 161 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA PM572 UT WOS:A1994PM57200008 PM 7522686 ER PT J AU LONE, YC BELLIO, M PROCHNICKACHALUFOUR, A OJCIUS, DM BOISSEL, N OTTENHOFF, THM KLAUSNER, RD ABASTADO, JP KOURILSKY, P AF LONE, YC BELLIO, M PROCHNICKACHALUFOUR, A OJCIUS, DM BOISSEL, N OTTENHOFF, THM KLAUSNER, RD ABASTADO, JP KOURILSKY, P TI ROLE OF THE CDR1 REGION OF THE TCR BETA-CHAIN IN THE BINDING TO PURIFIED MHC-PEPTIDE COMPLEX SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE AFFINITY; AVIDITY; BASOPHIL; MUTAGENESIS ID T-CELL RECEPTOR; ANTIGEN RECOGNITION; LYMPHOCYTE-T; ALPHA-CHAIN; MOLECULE; ANTAGONISTS; ACTIVATION; EXPRESSION; INDUCTION; TOLERANCE AB Single alanine substitutions were introduced into the CDR1 region of the beta chain of a K-d-restricted TCR. Mutants and wild-type TCR were attached to the zeta chain of the CD3 complex and expressed at the surface of a rat basophil cell line. Transfectants were tested for the binding of purified soluble K-d-peptide complexes. With this experimental system, accessory molecules are unlikely to play a major role and the contribution of each residue to the interaction can be addressed. Results show that all positions in the CDR1 region are involved in the binding to the K-d-peptide complex but at varying degrees. These effects are discussed in relation to a molecular model of the TCR. Comparison of these results with previous data obtained in a T cell hybridoma system suggests the existence of a threshold in the TCR affinity necessary for mature T cell activation. C1 INST PASTEUR,SERV INFORMAT SCI,F-75724 PARIS 15,FRANCE. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP LONE, YC (reprint author), INST PASTEUR,DEPT IMMUNOL,INSERM,U277,UNITE BIOL MOLEC GENE,25 RUE DR ROUX,F-75724 PARIS 15,FRANCE. RI Bellio, Maria/K-8470-2012 NR 38 TC 6 Z9 6 U1 0 U2 2 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 OCT PY 1994 VL 6 IS 10 BP 1561 EP 1565 DI 10.1093/intimm/6.10.1561 PG 5 WC Immunology SC Immunology GA PM818 UT WOS:A1994PM81800012 PM 7826946 ER PT J AU LEVINE, PH PALLESEN, G EBBESEN, P HARRIS, N EVANS, AS MUELLER, N AF LEVINE, PH PALLESEN, G EBBESEN, P HARRIS, N EVANS, AS MUELLER, N TI EVALUATION OF EPSTEIN-BARR-VIRUS ANTIBODY PATTERNS AND DETECTION OF VIRAL MARKERS IN THE BIOPSIES OF PATIENTS WITH HODGKINS-DISEASE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MONOCLONAL-ANTIBODIES; CELLS; EXPRESSION; GENOMES; LYMPHOMAS AB We assessed the relationship of Epstein-Barr virus (EBV) serology to the presence or absence of EBV genome in 39 cases of Hodgkin's disease (HD). Biopsies from patients included in 2 previous published studies, 1 involving patients from the United States (eastern Massachusetts) and 1 from Denmark, were evaluated fro EBV RNA (EBER-1) and latent membrane protein (LMP-1). The present of EBV in Reed-Sternberg cells in the biopsies correlated with the histologic subtype of HD (mixed cellularity and lymphocyte depletion) but not with IgG antibody titers against the viral capsid antigen (VCA). These data suggest that, unlike Burkitt's lymphoma, the IgG antibody against VCA is not predictive of the presence or absence of EBV in Reed-Sternberg cells in HD. The predictive value of other antibodies should be evaluated. (C) 1994 Wiley-Liss, Inc. C1 AARHUS KOMMUNE HOSP,IMMUNOPATHOL LAB,DK-8000 AARHUS,DENMARK. DANISH CANC SOC,DEPT VIRUS & CANC,DK-8000 AARHUS,DENMARK. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. RP LEVINE, PH (reprint author), NCI,VRIAL EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 25 TC 25 Z9 26 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 OCT 1 PY 1994 VL 59 IS 1 BP 48 EP 50 DI 10.1002/ijc.2910590111 PG 3 WC Oncology SC Oncology GA PJ348 UT WOS:A1994PJ34800010 PM 7927903 ER PT J AU MELLEMGAARD, A NIWA, S MEHL, ES ENGHOLM, G MCLAUGHLIN, JK OLSEN, JH AF MELLEMGAARD, A NIWA, S MEHL, ES ENGHOLM, G MCLAUGHLIN, JK OLSEN, JH TI RISK-FACTORS FOR RENAL-CELL CARCINOMA IN DENMARK - ROLE OF MEDICATION AND MEDICAL HISTORY SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID KIDNEY CANCER; HYPERTENSION; OBESITY AB Background. Several recent studies of risk factors for renal cell carcinoma have indicated that use of diuretics may increase risk of this cancer. It has also been suggested that use of weak analgesics, which are known to increase risk of cancer of the renal pelvis and ureter, may also be associated with an increased risk of renal cell carcinoma - the most frequent type of kidney cancer. Methods. A population-based case-control study was undertaken to investigate the role of diuretics, other anti-hypertensive drugs, analgesics, and medical history in the aetiology of renal cell carcinoma. The study base was the total Danish population, and 368 histologically verified cases and 396 sex- and age-matched controls who were interviewed from February 1989 to May 1992. Results. Response rates were 76% among cases and 79% among controls. We found no general increase in risk among users of diuretics or analgesics, although women taking loop diuretics and heavy users of acetyl salicylic acid had slightly increased risks. The use of nondiuretic anti-hypertensive medications was associated with decreased risk in women. We found non-significantly increased risks for history of hypertension and other cardiovascular disorders. We also observed elevated risks for urological disorders in both sexes which may be a result of recall bias. Conclusion. This study provides only limited support for the suggested association between risk of renal cell carcinoma and use of diuretics and analgesics. The coexistence of renal cell carcinoma and cardiovascular diseases could be caused by risk factors that are common to these conditions. C1 WESTAT CORP,ROCKVILLE,MD. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. RP MELLEMGAARD, A (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,BOX 839,DK-2100 COPENHAGEN,DENMARK. NR 23 TC 51 Z9 51 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 1994 VL 23 IS 5 BP 923 EP 930 DI 10.1093/ije/23.5.923 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PT303 UT WOS:A1994PT30300007 PM 7860172 ER PT J AU SCHUTZ, CG CHILCOAT, HD AF SCHUTZ, CG CHILCOAT, HD TI BREACH OF PRIVACY IN SURVEYS ON ADOLESCENT DRUG-USE - A METHODOLOGICAL INQUIRY SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article AB Privacy is considered an important issue for surveys of drug use, although few studies have directly assessed its impact, specifically on adolescent reporting. The present study tested for a possible inverse association between breaches of privacy during a national household survey on drug abuse and the prevalence of drug use reported by adolescents who participated in the survey. The study sample consisted of more than 2000 adolescents, 12-17 years old, who participated in the 1990 National Household Survey on Drug Abuse. These youths were interviewed in their households for the survey, and sometimes there were breaches in privacy during the interview, ranging from essentially no disturbance to constant presence of a third party, such as a parent. Using both cross-tabular and stratified analyses, as well as multiple logistic regression models, we found that adolescents less often reported involvement with tobacco, alcohol and controlled substances such as marijuana and cocaine when their parents were present during the interview session. This occurred primarily when the parents were present constantly, but to some extent also when there were less extensive breaches of privacy. On the other hand, more adolescents reported alcohol, tobacco or illicit drug involvement when a non-parent was present during the interview, compared to interviews with complete privacy. These findings are consistent with a small but growing body of evidence that level of privacy affects reporting in drug abuse surveys. They also point toward specific directions for future research that will help explain possible substantive implications of the observed associations. These include the possibility that parents who disturb the privacy of an interview session with an adolescent are engaging in close supervision and monitoring of a dependent child - a parenting behaviour that may have adaptive and generally beneficial consequences in relation to delayed onset or reduced risk of drug use for the offspring. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD 21218. RP SCHUTZ, CG (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 6 TC 9 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1049-8931 J9 INT J METHOD PSYCH JI Int. J. Methods Psychiatr. Res. PD OCT PY 1994 VL 4 IS 3 BP 183 EP 188 PG 6 WC Psychiatry SC Psychiatry GA PJ672 UT WOS:A1994PJ67200005 ER PT J AU MITCHELL, DS GUAN, XY MELTZER, PS AF MITCHELL, DS GUAN, XY MELTZER, PS TI DETECTION OF CHROMOSOME 12Q AMPLIFICATION IN SARCOMAS BY CHROMOSOME MICRODISSECTION AND INTERPHASE FISH SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CHROMOSOME 12Q AMPLIFICATION; SARCOMAS; CHROMOSOME MICRODISSECTION; INTERPHASE FISH ID FLUORESCENCE INSITU HYBRIDIZATION; SOFT-TISSUE SARCOMAS; GENE AMPLIFICATION; AMPLIFIED DNA; IDENTIFICATION; REGION; MDM2; TRANSLOCATIONS; TUMORS; PROBES AB We describe the microdissection of a homogeneously staining region (hsr) in the neuroblastoma cell line NGP-127 which contains the SAS gene. Fluorescence in situ hybridization (FISH) of this probe to NGP-127 cells confirms its derivation from the hsr, while FISH to normal chromosomes establishes that the hsr is composed of sequences from two segments of chromosome 12q. The hsr microdissection probe yields fluorescent signals which are sufficiently intense to readily identify amplification of homologous sequences in interphase nuclei. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT PEDIAT,ANN ARBOR,MI 48109. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 20 TC 2 Z9 2 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1994 VL 5 IS 4 BP 787 EP 792 PG 6 WC Oncology SC Oncology GA PG549 UT WOS:A1994PG54900010 PM 21559643 ER PT J AU ALBORESSAAVEDRA, J HENSON, DE MILCHGRUB, S AF ALBORESSAAVEDRA, J HENSON, DE MILCHGRUB, S TI INTRADUCTAL PAPILLARY CARCINOMA OF THE MAIN PANCREATIC DUCT SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Article; Proceedings Paper CT The NCI Workshop on Investigational Strategies for Detection and Intervention in Early-Stage Pancreatic Cancer CY APR 24-27, 1994 CL ANNAPOLIS, MD SP NCI, ORGAN SYST PROGRAM, DIV CANC BIOL DIAGNOSIS & CTR C1 NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. RP ALBORESSAAVEDRA, J (reprint author), UNIV TEXAS,SW MED CTR,DEPT PATHOL,DIV ANAT PATHOL,DALLAS,TX, USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD OCT-DEC PY 1994 VL 16 IS 2-3 BP 223 EP 224 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PN722 UT WOS:A1994PN72200025 ER PT J AU TULLY, JG WHITCOMB, RF ROSE, DL BOVE, JM CARLE, P SOMERSON, NL WILLIAMSON, DL EDENGREEN, S AF TULLY, JG WHITCOMB, RF ROSE, DL BOVE, JM CARLE, P SOMERSON, NL WILLIAMSON, DL EDENGREEN, S TI ACHOLEPLASMA-BRASSICAE SP-NOV AND ACHOLEPLASMA-PALMAE SP-NOV, 2 NON-STEROL-REQUIRING MOLLICUTES FROM PLANT-SURFACES SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID MYCOPLASMAS AB Two mollicutes (strains 0502(T) [T = type strain] and J233(T)), which were isolated from the surfaces of broccoli (Brassica oleracea var. italica) plants or the crown tissues of the coconut palm (Cocos nucifera), were capable of sustained growth in serum-free (or cholesterol-free) mycoplasma broth media. Examination by electron and dark-field microscopic techniques revealed that the cells of each strain were small, nonhelical, nonmotile, pleomorphic, and coccoid and that each cell was surrounded by a single cytoplasmic membrane. No evidence of a cell wall was found. The organisms were filterable and grew rapidly in most conventional mycoplasma culture medium formulations containing horse or fetal bovine sera under either aerobic or anaerobic conditions. The optimum temperature for growth of both organisms was 30 degrees C, but multiplication occurred over a temperature range from 18 to 37 degrees C. Both strains catabolized glucose, but did not hydrolyze arbutin, arginine, or urea. The genome size of strain 0502(T) was 1,215 kbp, and the DNA base composition (guanine-plus-cytosine content) was 35.5 mol%. The genome size of strain J233(T) was 1,610 kbp, and the DNA base composition was 30.0 mol%. The two isolates were not serologically related to each other or to the type strains of 11 previously described Acholeplasma species. Strain 0502 (= ATCC 49388) is the type strain of Acholeplasma brassicae sp. nov., and strain J233 (= ATCC 49389) is the type strain of Acholeplasma palmae sp. nov. C1 USDA,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. OHIO STATE UNIV,DEPT MICROBIOL,COLUMBUS,OH 43210. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. NAT RESOURCES INST,CHATHAM ME4 4TB,KENT,ENGLAND. RP TULLY, JG (reprint author), NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,BLDG 550,FREDERICK,MD 21702, USA. NR 36 TC 13 Z9 13 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1994 VL 44 IS 4 BP 680 EP 684 PG 5 WC Microbiology SC Microbiology GA PM262 UT WOS:A1994PM26200015 PM 7981098 ER PT J AU TULLY, JG WHITCOMB, RF HACKETT, KJ ROSE, DL HENEGAR, RB BOVE, JM CARLE, P WILLIAMSON, DL CLARK, TB AF TULLY, JG WHITCOMB, RF HACKETT, KJ ROSE, DL HENEGAR, RB BOVE, JM CARLE, P WILLIAMSON, DL CLARK, TB TI TAXONOMIC DESCRIPTIONS OF 8 NEW NON-STEROL-REQUIRING MOLLICUTES ASSIGNED TO THE GENUS MESOPLASMA SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID SUGAR-PHOSPHOTRANSFERASE SYSTEM; ACHOLEPLASMA-FLORUM; CLASSIFICATION; MYCOPLASMAS AB Twenty mollicute strains isolated primarily from insect hosts were characterized and arranged into eight new species in the genus Mesoplasma. Morphological examination of the organisms by electron and dark-field microscopic techniques revealed that the cells of each strain were small, nonhelical, nonmotile, pleomorphic, and coccoid and that each cell was surrounded by a single cytoplasmic membrane,vith no evidence of a cell wall. Although the new mollicutes grew well in media containing horse or fetal bovine serum, growth in serum-free or cholesterol-free medium occurred only when the medium contained 0.04% polyoxyethylene sorbitan (Tween 80). The optimum temperature for growth was usually 30 degrees C, but multiplication generally occurred over a temperature range of 10 to 32 degrees C. All strains catabolized glucose. Most strains did not hydrolyze arginine or urea, although three related strains isolated from fireflies (the strain PUPA-2(T) [T = type strain] group) did hydrolyze arginine. The genome sizes ranged from 825 to 930 kbp, and the DNA base compositions (guanine-plus-cytosine contents) ranged from 26.5 to 31.6 mol%. The proposed type strains of the eight new species were not serologically related to the type strains of four other Mesoplasma species, five Entomoplasma species, 11 Acholeplasma species, and 100 Mycoplasma species and subspecies. Strain PS-1 (= ATCC 49582) is the type strain of Mesoplasma pleciae sp. nov., strain PUPA-2 (= ATCC 49581) is the type strain of Mesoplasma photuris sp. nov., strain YJS (= ATCC 43706) is the type strain of Mesoplasma syrphidae sp. nov., strain CHPA-2 (= ATCC 49578) is the type strain of Mesoplasma chauliocola sp. nov., strain ELCA-2 (= ATCC 49579) is the type strain of Mesoplasma corruscae sp. nov., strain GRUA-1 (= ATCC 49580) is the type strain of Mesoplasma grammopterae sp. nov., strain BARC 779 (= ATCC 49583) is the type strain of Mesoplasma coleopterae sp. nov., and strain BARC 857 (= ATCC 49584) is the type strain of Mesoplasma tabanidae sp. nov. C1 USDA,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. RP TULLY, JG (reprint author), NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,BLDG 550,FREDERICK,MD 21702, USA. NR 36 TC 11 Z9 11 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1994 VL 44 IS 4 BP 685 EP 693 PG 9 WC Microbiology SC Microbiology GA PM262 UT WOS:A1994PM26200016 PM 7726910 ER PT J AU BERNSTEIN, SL KUTTY, G WIGGERT, B ALBERT, DM NICKERSON, JM AF BERNSTEIN, SL KUTTY, G WIGGERT, B ALBERT, DM NICKERSON, JM TI EXPRESSION OF RETINA-SPECIFIC GENES BY MOUSE RETINOBLASTOMA CELLS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE MURINE RETINOBLASTOMA; INTERPHOTORECEPTOR RETINOID BINDING PROTEIN (IRBP); REVERSE-TRANSCRIPTION BASED POLYMERASE CHAIN REACTION (RT-PCR); MESSENGER RNA; RETINA-SPECIFIC GENES ID BINDING PROTEIN IRBP; MESSENGER-RNA; DIFFERENTIATION; OPSIN; MICE AB Purpose. Two cell lines derived from ocular tumors of a transgenic mouse expressing the SV40 large T antigen have been established as models of human retinoblastoma. One line, TM, originated from a metastasis, and the other, TE, originated from the primary tumor. The authors compared these two lines with the normal adult mouse eye by analysis of the expression of five photoreceptor cell-specific proteins: IRBP, opsin, rod- and cone-specific transducins, and S-antigen. The authors sought to determine which of these proteins was expressed qualitatively and to examine semi-quantitatively for changes in the levels of expression in the cell lines. Method. Western blot analysis was used to detect photoreceptor-specific intracellular or secreted proteins. Total RNA was prepared from cultured cells or from mouse adult whole eye. Specific messenger levels in total RNA were determined either by northern hybridization analysis or by a semiquantitative polymerase chain reaction (PCR), coupled to complementary DNA (cDNA) substrates prepared from total RNA. Results. IRBP was present in the retinoblastoma cell lines and secreted into the medium. Neither S-antigen nor opsin were detectable by immunoblotting. IRBP and cone transducin mRNA were present in both cell lines. In contrast, opsin, rod transducin, and S-Antigen mRNAs were not detectable by PCR. p-actin was present in the mRNA populations of whole eye and retinoblastoma. SV40 large T antigen mRNA was present only in retinoblastoma cells. Conclusions. IRBP and cone transducin expression in mouse retinoblastoma cells is independent of signaling provided directly or indirectly through large T antigen or Rb-105 regulatory cascades. The pattern of photoreceptor-specific gene expression is similar to that seen in human retinoblastoma cell lines. These murine-derived cell lines may be useful as a tool to study IRBP and cone transducin expression in vitro and to determine early retinoblast expression patterns in the mouse. C1 UNIV WISCONSIN,DEPT OPHTHALMOL & VISUAL SCI,MADISON,WI. EMORY UNIV,DEPT OPHTHALMOL,ATLANTA,GA. RP BERNSTEIN, SL (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1994 VL 35 IS 11 BP 3931 EP 3937 PG 7 WC Ophthalmology SC Ophthalmology GA PM510 UT WOS:A1994PM51000020 PM 7928191 ER PT J AU DUNN, DT NEWELL, ML MAYAUX, MJ KIND, C HUTTO, C GOEDERT, JJ ANDIMAN, W AF DUNN, DT NEWELL, ML MAYAUX, MJ KIND, C HUTTO, C GOEDERT, JJ ANDIMAN, W TI MODE OF DELIVERY AND VERTICAL TRANSMISSION OF HIV-1 - A REVIEW OF PROSPECTIVE STUDIES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Note ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTION; MOTHER; WOMEN C1 INST CHILD HLTH,DEPT BIOSTAT & EPIDEMIOL,LONDON WC1N 1EH,ENGLAND. KANTONSSPITAL,ST GALLEN,SWITZERLAND. UNIV MIAMI,MIAMI,FL 33152. NCI,ROCKVILLE,MD. YALE UNIV,NEW HAVEN,CT. RI SHCS, MoCHIV/G-4081-2011; SHCS, ch/G-4077-2011; SHCS, all/G-4072-2011; OI Newell, Marie-Louise/0000-0002-1074-7699 NR 16 TC 92 Z9 95 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT PY 1994 VL 7 IS 10 BP 1064 EP 1066 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH776 UT WOS:A1994PH77600010 PM 8083824 ER PT J AU EHMANN, WC EYSTER, ME WILSON, SE ANDES, WA GOEDERT, JJ AF EHMANN, WC EYSTER, ME WILSON, SE ANDES, WA GOEDERT, JJ TI RELATIONSHIP OF CD4 LYMPHOCYTE COUNTS TO SURVIVAL IN A COHORT OF HEMOPHILIACS INFECTED WITH HIV SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE SURVIVAL; HIV-INFECTED HEMOPHILIACS; CD4 LYMPHOCYTE COUNTS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; AIDS; RISK; DEATH AB Although CD4 positive lymphocyte counts are important predictors of clinical events in persons infected with human immunodeficiency virus (HIV), little is known about their predictive value for survival. We analyzed CD4 counts obtained regularly since 1983 with regard to survival in a multicenter cohort study of 921 HIV-infected hemophiliacs of whom 177 have died. Dates of seroconversion were determined from stored serum samples. Cumulative mortality and actuarial survival rates were calculated from the first time the mean of two consecutive CD4 counts decreased from levels of >500 to 20-499, 100-199, 50-99, and <50 cells/mu l. The death rate per 100 patient years of observation was 0.87 (95% CI 0.27, 1.47) for those with CD4 counts of >500 cells/mu l and increased progressively to 26.23 (95% CI 21.29, 31.17) for those with CD4 counts of <50/mu l. HIV-related deaths occurred in 50 of 58 who died with CD4 counts of <300/mu l compared to 0 of 6 who died with CD4 counts of >500/mu l. The median CD4 count most proximal to death was 39.5 (range, 1-945). The 10-year actuarial estimate of survival from seroconversion was 77.3 +/- 2% for 546 persons who seroconverted at age greater than or equal to 18 years compared to 90.5 +/- 2% for 375 persons who seroconverted at age <18. Survival decreased at each CD4 level to a median of 27 months at CD4 counts of <50/mu l. At each CD4 level, younger patients survived longer than older patients. In this cohort, death was 32 times more frequent with very low CD4 counts (<50 cells/mu l) compared to high CD4 counts (>500 cells/mu l). However, among those with very low CD4 counts, survival was much longer than had previously been described and younger age at seroconversion was a positive prognostic factor at all CD4 levels. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. COMP SCI CORP,ROCKVILLE,MD. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. RP EHMANN, WC (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT MED,DIV HEMATOL,POB 850,HERSHEY,PA 17033, USA. NR 13 TC 33 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT PY 1994 VL 7 IS 10 BP 1095 EP 1098 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PH776 UT WOS:A1994PH77600015 PM 7916052 ER PT J AU CONE, EJ HILLSGROVE, MJ JENKINS, AJ KEENAN, RM DARWIN, WD AF CONE, EJ HILLSGROVE, MJ JENKINS, AJ KEENAN, RM DARWIN, WD TI SWEAT TESTING FOR HEROIN, COCAINE, AND METABOLITES SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID EXCRETION; SALIVA; PERSPIRATION; HAIR RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 20 TC 89 Z9 94 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1994 VL 18 IS 6 BP 298 EP 305 PG 8 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA PH544 UT WOS:A1994PH54400002 PM 7823536 ER PT J AU JENKINS, AJ KEENAN, RM HENNINGFIELD, JE CONE, EJ AF JENKINS, AJ KEENAN, RM HENNINGFIELD, JE CONE, EJ TI PHARMACOKINETICS AND PHARMACODYNAMICS OF SMOKED HEROIN SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DELIVERY; MORPHINE; SMOKING; COCAINE C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 22 TC 74 Z9 79 U1 1 U2 8 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1994 VL 18 IS 6 BP 317 EP 330 PG 14 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA PH544 UT WOS:A1994PH54400005 PM 7823539 ER PT J AU SAMUELS, DS MACH, KE GARON, CF AF SAMUELS, DS MACH, KE GARON, CF TI GENETIC-TRANSFORMATION OF THE LYME-DISEASE AGENT BORRELIA-BURGDORFERI WITH COUMARIN-RESISTANT GYRB SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA GYRASE; LINEAR CHROMOSOME; NOVOBIOCIN; TOPOISOMERASES; SELECTION; PROTEIN; RECOMBINATION; MUTATIONS; MECHANISM; FRAGMENT AB No useful method to genetically manipulate Borrelia burgdorferi, the causative agent of Lyme disease, has been developed previously. We have used resistance to the coumarin antibiotic coumermycin A(1), an inhibitor of DNA gyrase, as a genetic marker to monitor the transformation of B. burgdorferi by electroporation. Introduction of site directed mutations into the gyrB gene demonstrated that transformation was successful, provided evidence that homologous recombination occurs on the chromosome, and established that mutations at Arg-133 of DNA gyrase B confer coumermycin A(1) resistance in B. burgdorferi. The coumermycin A(1)-resistant gyrB marker and genetic transformation can now be applied toward dissecting the physiology and pathogenesis of the Lyme disease agent on a molecular genetic level. RP SAMUELS, DS (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 NR 45 TC 97 Z9 101 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1994 VL 176 IS 19 BP 6045 EP 6049 PG 5 WC Microbiology SC Microbiology GA PJ904 UT WOS:A1994PJ90400021 PM 7928965 ER PT J AU ROSNER, JL SLONCZEWSKI, JL AF ROSNER, JL SLONCZEWSKI, JL TI DUAL REGULATION OF INAA BY THE MULTIPLE ANTIBIOTIC-RESISTANCE (MAR) AND SUPEROXIDE (SOXRS) STRESS-RESPONSE SYSTEMS OF ESCHERICHIA-COLI SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OXIDATIVE-STRESS; POSITIVE CONTROL; OMPF PORIN; EXPRESSION; LOCUS; GENE; REGULON; K-12; SALICYLATE; ACTIVATION AB The roles of the marRAB (multiple antibiotic resistance) operon and soxRS (superoxide response) genes in the regulation of inaA, an unlinked weak-acid-inducible gene, were studied. inaA expression was estimated from the beta-galactosidase activity of a chromosomal inaA1::lacZ transcriptional fusion. marR mutations that elevate marRAB transcription and engender multiple antibiotic resistance elevated inaA expression by 10- to 20-fold over that of the wild-type. Similarly, one class of inaA constitutive mutants that mapped to the mar region were multiply antibiotic resistant. Overexpression of marA alone on a multicopy plasmid caused high constitutive expression of inaA in a strain with an extensive (39-kbp) marRAB deletion. Salicylate, an inducer of marRAB and of an unidentified mar-independent antibiotic resistance system, induced inaA by 6-fold. A portion of this induction was: also mar independent. Two soxRS constitutive mutants that were tested showed elevated levels of inaA. Paraquat, an inducer of the soxRS system, elevated inaA expression by 6- to 9-fold. This induction was soxRS dependent and hot mar dependent, whereas induction of inaA by salicylate was not dependent on soxRS. Paraquat induced resistance to norfloxacin in the mar-deleted strain but not in a soxRS-deleted strain. Thus, induction of multiple antibiotic resistance and inaA by salicylate occurs via mar and an unidentified pathway, while induction by paraquat occurs via soxRS. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. KENYON COLL,DEPT BIOL,GAMBIER,OH 43022. NR 38 TC 78 Z9 79 U1 1 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 OCT PY 1994 VL 176 IS 20 BP 6262 EP 6269 PG 8 WC Microbiology SC Microbiology GA PK772 UT WOS:A1994PK77200015 PM 7928997 ER PT J AU BALASUNDARAM, D XIE, QW TABOR, CW TABOR, H AF BALASUNDARAM, D XIE, QW TABOR, CW TABOR, H TI THE PRESENCE OF AN ACTIVE S-ADENOSYLMETHIONINE DECARBOXYLASE GENE INCREASES THE GROWTH DEFECT OBSERVED IN SACCHAROMYCES-CEREVISIAE MUTANTS UNABLE TO SYNTHESIZE PUTRESCINE, SPERMIDINE, AND SPERMINE SO JOURNAL OF BACTERIOLOGY LA English DT Note ID ORNITHINE DECARBOXYLASE; ALPHA-DIFLUOROMETHYLORNITHINE; ESCHERICHIA-COLI; MAMMALIAN-CELLS; YEAST; INHIBITION; ACCUMULATION; POLYAMINES AB Saccharomyces cerevisiae spe1 Delta SPE2 mutants (lacking ornithine decarboxylase) and spe1 Delta spe2 Delta mutants (lacking both ornithine decarboxylase and S-adenosylmethionine decarboxylase) are equally unable to synthesize putrescine, spermidine, and spermine and require spermidine or spermine for growth in amine free media. The cessation of growth, however, occurs more rapidly in spe1 Delta SPE2 cells than in SPE1 spe2 Delta or spe1 Delta spe2 Delta, cells. Since spe1 Delta SPE2 cells can synthesize decarboxylated adenosylmethionine (dcAdoMet), these data indicate that dcAdoMet may be toxic to amine-deficient cells. RP BALASUNDARAM, D (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,BETHESDA,MD 20892, USA. NR 19 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1994 VL 176 IS 20 BP 6407 EP 6409 PG 3 WC Microbiology SC Microbiology GA PK772 UT WOS:A1994PK77200033 PM 7929015 ER PT J AU NIMS, RW LUBET, RA DIWAN, BA MELLINI, DW UTERMAHLEN, WE THOMAS, PE AF NIMS, RW LUBET, RA DIWAN, BA MELLINI, DW UTERMAHLEN, WE THOMAS, PE TI HEPATIC CYTOCHROME-P450 2B INDUCTION BY ETHYL/PHENYL-SUBSTITUTED CONGENERS OF PHENOBARBITAL IN THE B6C3F1 MOUSE SO JOURNAL OF BIOCHEMICAL TOXICOLOGY LA English DT Article DE PHARMACODYNAMICS; INDUCTION OF P450 2B SUBFAMILY; MOUSE LIVER; PHENOBARBITAL; 5-ETHYL-5-PHENYLHYDANTOIN ID MONO-OXYGENASE ACTIVITY; RAT-LIVER; N-NITROSODIETHYLAMINE; ENZYME-INDUCTION; GENE-EXPRESSION; 1,4-BIS<2-(3,5-DICHLOROPYRIDYLOXY)>BENZENE; ISOZYMES; SUBFAMILY; 5-ETHYL-5-PHENYLHYDANTOIN; DEALKYLATION AB The abilities of structural congeners of phenobarbital to induce immunoreactive hepatic cytochrome P450 2B (CYP2B) protein and associated catalytic activity (benzyloxyresorufin 0-dealkylation) in the male B6C3F1 mouse were examined. Interspecies differences in inducing ability were examined through comparison of the results with induction data obtained previously with the male F344/NCr rat. The congeners were administered in the diet for 2 weeks at concentrations equimolar to 500 ppm of the prototype CYP2B inducer, phenobarbital. Of the series of compounds tested, phenobarbital was the most effective inducer of benzyloxyresorufin 0-dealkylation and immunoreactive CYP2B protein, with 2-ethyl-2-phenylsuccinimide, 5-ethyl-5-phenylhydantoin, primidone, and glutethimide being only 19-42% as effective. 5-Ethyl-5-phenyloxazolidinedione and the ring-opened and decarboxylated congeners, N(2-ethyl-2-phenylacetyl)urea and 2-ethyl-2-phenylmalonamide, displayed minimal induction of these catalytic activities. Dose-response experiments performed with 5-ethyl-5-phenylhydantoin indicated that the intrinsic CYP2B-inducing activity of this congener was as great as that of phenobarbital in the mouse, although a fourfold greater dietary concentration of this hydantoin (2000 ppm) was required to elicit a response equivalent to that caused by 500 ppm phenobarbital. When extent of induction was related to serum total xenobiotic concentration rather than to administered dietary concentration, the potencies of the two congeners were determined to be more similar (58 vs. greater than or equal to 78 mu M for phenobarbital and 5-ethyl-5-phenylhydantoin, respectively). C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RUTGERS STATE UNIV,COLL PHARM,DEPT BIOL CHEM,PISCATAWAY,NJ 08855. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0887-2082 J9 J BIOCHEM TOXICOL JI J. Biochem. Toxicol. PD OCT PY 1994 VL 9 IS 5 BP 269 EP 278 DI 10.1002/jbt.2570090507 PG 10 WC Toxicology SC Toxicology GA PP045 UT WOS:A1994PP04500006 PM 7853362 ER PT J AU INANO, K CURTIS, SW KORACH, KS OMATA, S HORIGOME, T AF INANO, K CURTIS, SW KORACH, KS OMATA, S HORIGOME, T TI HEAT-SHOCK PROTEIN-90 STRONGLY STIMULATES THE BINDING OF PURIFIED ESTROGEN-RECEPTOR TO ITS RESPONSIVE ELEMENT SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE ESTROGEN RECEPTOR; ESTROGEN RESPONSIVE ELEMENT; HEAT SHOCK PROTEIN 90; HSP 90; MOLTEN GLOBULE ID ROUS-SARCOMA VIRUS; CELL GLUCOCORTICOID RECEPTOR; REGULATED EIF-2-ALPHA KINASE; MOLTEN-GLOBULE STATE; DNA-BINDING; HORMONE-BINDING; MONOCLONAL-ANTIBODIES; TRANSFORMING PROTEIN; STEROID-RECEPTORS; POLYCLONAL ANTIBODIES AB We previously showed that the 9 S estrogen receptor (ER) could be reconstituted from purified ER and purified heat shock protein 90 (hsp 90). So, we investigated the role of hsp 90 in the binding of purified ER to an estrogen responsive element (ERE) by using the reconstitution system. ER purified from calf uterus showed a very low binding capacity to an ERE from the vitellogenin A2 gene in the gel mobility shift assay. However, the binding was strongly stimulated by reconstitution with hsp 90 and was proportional to the amount of reconstituted 9 S ER. Hsp 70, a typical molecular chaperone and a component of some steroid receptors, did not cause similar stimulation. The equilibrium dissociation constants (K-d) of the occupied and unoccupied 9 S ER for the ERE were the same as each other, indicating that the binding of ER to the ERE was independent of the ligand. H222, a monoclonal antibody which binds to the hormone-binding domain (HBD) of ER, recovered the high affinity ER-ERE binding. The binding of hsp 90 to ER suppressed the Triton X-100 stimulated estradiol-dissociation from the ER. The sedimentation coefficients and Stokes' radii of the purified and unpurified cytosolic ER were compared, and it was shown that the purified ER was not unfolded and had a rather compact structure, similar to the cytosolic ER. From these results and others, the mechanism underlying stimulation of the ER-ERE binding by hsp 90 was speculated to be as follows: i) purified ER exists in a molten globule state, ii) hsp 90 recognizes the state and binds to the HED, and iii) this binding changes the ER to a native form, and thus makes possible the binding of ER to the ERE. C1 NIIGATA UNIV,GRAD SCH SCI & TECHNOL,DEPT BIOSYST SCI,NIIGATA 95021,JAPAN. NIIGATA UNIV,FAC SCI,DEPT BIOCHEM,NIIGATA 95021,JAPAN. NIEHS,RECEPTOR BIOL SECT,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 63 TC 27 Z9 28 U1 0 U2 1 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD OCT PY 1994 VL 116 IS 4 BP 759 EP 766 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK736 UT WOS:A1994PK73600008 PM 7883750 ER PT J AU HANSFORD, RG AF HANSFORD, RG TI PHYSIOLOGICAL-ROLE OF MITOCHONDRIAL CA2+ TRANSPORT SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE OXIDATIVE PHOSPHORYLATION; ION TRANSPORT; TRICARBOXYLATE CYCLE; CARDIOMYOPATHY ID FREE CALCIUM-CONCENTRATION; FREE CA-2+ CONCENTRATION; PERFUSED RAT-HEART; 2-OXOGLUTARATE DEHYDROGENASE COMPLEX; MAGNETIC-RESONANCE SPECTROSCOPY; POSITIVE INOTROPIC AGENTS; CYTOSOLIC FREE CALCIUM; MOUSE SENSORY NEURONS; MATRIX FREE CA-2+; PYRUVATE-DEHYDROGENASE AB A model has been proposed in which mitochondrial Ca2+ ion transport serves to regulate mitochondrial matrix free Ca2+ ([Ca2+](m)), with the advantage to the animal that this allows the regulation of pyruvate dehydrogenase and the tricarboxylate cycle in response to energy demand. This article examines recent evidence for dehydrogenase activation and for increases in [Ca2+](m) in response to increased tissue energy demands, especially in cardiac myocytes and in heart. It critiques recent results on beat-to-beat variation in [Ca2+](m) in cardiac muscle and also briefly surveys the impact of mitochondrial Ca2+ transport on transient changes in cytosolic free Ca2+ in excitable tissues. Finally, it proposes that a failure to elevate [Ca2+](m) sufficiently in response to work load may underlie some cardiomyopathies of metabolic origin. RP HANSFORD, RG (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 132 TC 153 Z9 156 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD OCT PY 1994 VL 26 IS 5 BP 495 EP 508 DI 10.1007/BF00762734 PG 14 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA PV546 UT WOS:A1994PV54600004 PM 7896765 ER PT J AU JIANG, SP RAGHUNATHAN, G TING, KL XUAN, JC JERNIGAN, RL AF JIANG, SP RAGHUNATHAN, G TING, KL XUAN, JC JERNIGAN, RL TI GEOMETRIES, CHARGES, DIPOLE-MOMENTS AND INTERACTION ENERGIES OF NORMAL, TAUTOMERIC AND NOVEL BASES SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID NUCLEIC-ACID BASES; DOUBLE-HELICAL FRAGMENTS; ENZYMATIC INCORPORATION; MOLECULAR-INTERACTIONS; ATOMIC RESOLUTION; GENETIC ALPHABET; DIFFRACTION DATA; DNA; RNA; CRYSTAL AB Ab initio molecular orbital calculations with the STO-3G and 4-31G basis sets are performed to study the geometries and interactions of natural and ''novel'' Watson-Crick base pairs, as well as some non-Watson-Crick base pairs. First the optimized geometries of bases are determined using the STO-3G basis set, and then for the base pairs with the STO-3G and 4-31G basis sets. Interaction energies of these base pairs are evaluated, and their relative stabilities are discussed. Hydrogen bond features, partial charges and dipole moments of the base pairs are described. The calculated stabilities are in reasonable agreement with the limited available experimental data from thermal melting studies. Hydrogen bond geometries at the 4-31G level are in good agreement with the crystal structure data. The order of relative stabilities is found to be: iG:iC > G:C. G:T* > rG:rC > A*:C > Am:U > pi:kappa K > chi:kappa > G*:T > A:C* > U = AT where, A*, T*, G* and C* are tautomers, iG and iC are iso-G and iso-CI Am is 2-amino adenine, chi is xanthosine, kappa is 2,4-diaminopyrimidine, pi is 7-methyloxoformycin B, rG is modified guanine with substitutions at positions 5 and 7, and rC is modified cytosine with a substitution at position 6. Pairing strengths with modified bases may affect the efficiency of protein production. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BRP,CRYSTALLOG LAB,FREDERICK,MD 21702. RP JIANG, SP (reprint author), NCI,MATH BIOL LAB,BETHESDA,MD 20892, USA. RI Jernigan, Robert/A-5421-2012 NR 47 TC 20 Z9 21 U1 0 U2 5 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 OCT PY 1994 VL 12 IS 2 BP 367 EP 382 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW099 UT WOS:A1994PW09900007 PM 7702775 ER PT J AU JIANG, SP JERNIGAN, RL TING, KL SYI, JL RAGHUNATHAN, G AF JIANG, SP JERNIGAN, RL TING, KL SYI, JL RAGHUNATHAN, G TI STABILITY AND COOPERATIVITY OF NUCLEIC-ACID BASE TRIPLETS SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID INTRAMOLECULAR DNA TRIPLEX; HELIX FORMATION; MOLECULAR-STRUCTURE; SEQUENCE; STRAND; FORM; D(T)N.D(A)N.D(T)N; POLYNUCLEOTIDES; RECOGNITION; ASSIGNMENTS AB Geometries and stabilities of various base triplets have been studied using ab initio quantum chemical methods. Their optimized geometries are determined using the STO-3G basis set, and those of Hoogsteen and reverse Hoogsteen base pairs are evaluated with the 4-31 G basis set. Moreover, the preferred hydrogen bond patterns of the bases in triple helices are discussed. A cooperative effect for base pairing in triplets is presented, and it can be either positive or negative. Almost all base triplets that contain Watson-Crick G:C base pairs show a positive cooperativity. Conversely, the base triplets with Watson-Crick A:T base pairs mostly display a negative cooperativity. The interaction energies of base triplets are reported and the relative stabilities of base triplets are found as follows: A(+).GC > C+.GC(H)> C+.GC(rH)> G.GC(H)> G.GC(rH)> A.GC > T.AT(rH)> U.AU(H)> U.AT(H) > A.AT > G.AT > T.AT(m) > G.TA(2) > G.TA(1) H and rH denote the Hoogsteen and reverse Hoogsteen positions of the third base that would lead to parallel and antiparallel orientations respectively of the third chain with respect to the Watson-Crick paired purine chain. 'm' denotes the middle pairing scheme, in which the third base hydrogen bonds to both bases of Watson-Crick pair. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CTR BIOMED SUPERCOMP,FREDERICK,MD 21702. RP JIANG, SP (reprint author), NCI,MATH BIOL LAB,BLDG 10,BETHESDA,MD 20892, USA. RI Jernigan, Robert/A-5421-2012 NR 51 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 OCT PY 1994 VL 12 IS 2 BP 383 EP 399 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW099 UT WOS:A1994PW09900008 PM 7702776 ER PT J AU MACNEIL, RL SHENG, N STRAYHORN, C FISHER, LW SOMERMAN, MJ AF MACNEIL, RL SHENG, N STRAYHORN, C FISHER, LW SOMERMAN, MJ TI BONE SIALOPROTEIN IS LOCALIZED TO THE ROOT SURFACE DURING CEMENTOGENESIS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MINERALIZED-TISSUE FORMATION; MESSENGER-RNA; DEVELOPMENTAL EXPRESSION; MURINE PERIODONTIUM; CELLS; ATTACHMENT; OSTEOPONTIN; MATRIX; BSP; DIFFERENTIATION AB Bone sialoprotein (BSP), an ROD-containing protein with cell attachment properties, is believed to play a regulatory role in the biomineralization of various connective tissues. To determine its possible role in tooth root formation, murine dentoalveolar tissues at sequential phases of development were analyzed immunohistochemically for the presence of BSP. BSP was localized to alveolar bone and cementum at time points associated with initial mineralization of these tissues. In addition, northern blot analyses of dental follicle tissue at day 27 of tooth development indicated that BSP mRNA is expressed by dental follicle cells at a time point coincident with the initiation of cementogenesis on the peripheral tooth root surface. Collectively, these findings indicate that BSP may play an important role in the formation and mineralization of cementum. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,ANN ARBOR,MI 48109. RP MACNEIL, RL (reprint author), UNIV MICHIGAN,SCH DENT,DEPT PERIODONT PREVENT & GERIATR,1011 N UNIV,ANN ARBOR,MI 48109, USA. FU NIDCR NIH HHS [DE09532] NR 50 TC 87 Z9 91 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1994 VL 9 IS 10 BP 1597 EP 1606 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ111 UT WOS:A1994PJ11100012 PM 7817806 ER PT J AU YU, JC GUTKIND, JS MAHADEVAN, D LI, WQ MEYERS, KA PIERCE, JH HEIDARAN, MA AF YU, JC GUTKIND, JS MAHADEVAN, D LI, WQ MEYERS, KA PIERCE, JH HEIDARAN, MA TI BIOLOGICAL FUNCTION OF PDGF-INDUCED PI-3 KINASE-ACTIVITY - ITS ROLE IN ALPHA-PDGF RECEPTOR-MEDIATED MITOGENIC SIGNALING SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PHOSPHOLIPASE-C-GAMMA; GTPASE-ACTIVATING PROTEIN; PHOSPHATIDYLINOSITOL-3 KINASE; TYROSINE PHOSPHORYLATION; EGF RECEPTOR; BETA-RECEPTOR; MAP KINASE; NIH/3T3 CELLS; INSERT DOMAIN AB The tyrosine phosphorylation sites in the human alpha PDGF receptor (alpha PDGFR) required for association with PI-3 kinase have been identified as tyrosines 731 and 742. Mutation of either tyrosine substantially reduced PDGF-induced PI-3 kinase activity but did not impair the receptor-mediated mitogenic response. We sought to determine whether PDGF-induced PI-3 kinase activity could be further ablated so as to exclude a low threshold requirement for PDGFR signal transduction. Thus, we mutated both tyrosine 731 and 742 and expressed the double mutant (Y731F/Y742F) in 32D hematopoietic cells. In such transfectants, PDGF induced no detectable receptor-associated or anti-P-Tyr recoverable PI-3 kinase activity, Under the same conditions, neither mobility shift of raf-1 nor tyrosine phosphorylation of either PLC(gamma) or MAP kinase was impaired. 32D transfectants expressing the double mutant showed wild-type alpha PDGFR levels of mitogenic and chemotactic responses to PDGF. To examine the effect of the double mutation in cells that normally respond to PDGF, we generated chimeras in which the cytoplasmic domains of wild-type alpha PDGFR, Y731F, and Y731F/Y742F were linked to the extracellular domain of colony-stimulating factor-1 (CSF-1) receptor (fms). After introduction of the chimeric receptors into mouse NIH/3T3 fibroblasts, the ability of CSF-1 to stimulate growth of these transfectants was examined. Our data show that all these chimeric receptors exhibited similar abilities to mediate CSF-1-stimulated cell growth. These findings lead us to conclude that PDGF-induced PI-3 kinase activity is not required for PDGF-stimulated mitogenic pathway in both NIH/3T3 fibroblasts and 32D hematopoietic cells. C1 NCI 371E24,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NIDR 30211,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 47 TC 35 Z9 35 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1994 VL 127 IS 2 BP 479 EP 487 DI 10.1083/jcb.127.2.479 PG 9 WC Cell Biology SC Cell Biology GA PM416 UT WOS:A1994PM41600016 PM 7929590 ER PT J AU MASTORAKOS, G WEBER, JS MAGIAKOU, MA GUNN, H CHROUSOS, GP AF MASTORAKOS, G WEBER, JS MAGIAKOU, MA GUNN, H CHROUSOS, GP TI HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVATION AND STIMULATION OF SYSTEMIC VASOPRESSIN SECRETION BY RECOMBINANT INTERLEUKIN-6 IN HUMANS - POTENTIAL IMPLICATIONS FOR THE SYNDROME OF INAPPROPRIATE VASOPRESSIN SECRETION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; FREELY-MOVING RATS; TUMOR-NECROSIS-FACTOR; PLASMA ADRENOCORTICOTROPIN; ARGININE-VASOPRESSIN; MEDIAN-EMINENCE; HORMONE; CYTOKINES; RESPONSES; STRESS AB We recently demonstrated that sc administered interleukin-6 (IL-6) strongly stimulates the human hypothalamic-pituitary-adrenal (HPA) axis, with mild toxicity and no hypotensive effects. In this study, we evaluated the response of the human HPA axis to escalating iv doses of recombinant IL-6 in six patients with cancer and good performance status who received daily, every 8 h, three equal doses of 0.3-30 mu g/kg IL-6. The plasma levels of IL-6 assayed by a specific enzyme-linked immunosorbent assay during the 4 h following the first IL-6 injection were elevated for 2-4 h, proportionally to the amount of injected IL-6. Administration of the cytokine was followed by marked elevations of plasma ACTH (53.0-98.6 pmol/L) and cortisol (824.9-1729.9 nmol/L) independently of the IL-6 dose administered, suggesting that the doses employed were at the tap of the dose-response curve for these hormones. Interestingly, plasma arginine vasopressin (AVP) levels were also elevated during the 2 h after IL-6 injection in all patients who received a dose of 3 mu g/kg or more, suggesting that IL-6 activated the magnocellular AVP-secreting neurons and that it might be involved in the syndrome of inappropriate AVP secretion. Cortisol elevations with peaks similar to those observed after the first injection of IL-6 were also detected in plasma sampled every 2 h after the second and third injections, suggesting that there was no rapid tachyphylaxis in response to IL-6 administration. Plasma IL-1 beta and tumor necrosis factor-alpha concentrations, assayed by specific enzyme-linked immunosorbent assays during the 4 h after the first IL-6 injection, were either within the normal range or undetectable, confirming in vitro observations that IL-6 does not stimulate IL-1 beta or tumor necrosis factor-alpha secretion and suggesting that it exerts its effect on the HPA axis and AVP secretion independently of them. We conclude that IL-6 is a potent stimulator of the human HPA axis and a secretagogue of magnocellular AVP secretion, which might be employed as a challenge test of the axis and the magnocellular AVP neuron. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NCI, SURG BRANCH, BETHESDA, MD 20892 USA. SANDOZ PHARMACEUT INC, CYTOKINE DEV UNIT, E HANOVER, NJ 07936 USA. NR 32 TC 167 Z9 169 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 OCT PY 1994 VL 79 IS 4 BP 934 EP 939 DI 10.1210/jc.79.4.934 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200003 PM 7962300 ER PT J AU ABRAMS, SA YERGEY, AL HEANEY, RP AF ABRAMS, SA YERGEY, AL HEANEY, RP TI RELATIONSHIP BETWEEN BALANCE AND DUAL TRACER ISOTOPIC MEASUREMENTS OF CALCIUM-ABSORPTION AND EXCRETION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STABLE ISOTOPES; METABOLISM; CHILDREN; HUMANS; AGE AB Calcium (Ca) absorption was measured by the balance method and the dual tracer isotopic method in 462 studies of adult women. Results for both fractional absorption and net Ca balance were similar using the 2 methods. Slightly higher values (mean difference, 0.031 +/- 0.092) were found for fractional absorption measured by the balance method than by the isotopic method. No differences in fractional absorption between the methods were seen at a fractional absorption less than 25%. Variability in the data was greater from the balance than the isotopic method. Endogenous fecal Ca excretion was directly related to Ca intake, with an estimated value of 70-80 mg/day for a Ca intake less than 200 mg/day. These findings support the usefulness and accuracy of isotope-based measures of mineral absorption. No evidence is found from these or previous data to suggest that the process of isotopic equilibration falsely increases estimates of absorption or endogenous excretion in tracer studies. Isotopic techniques allow studies of calcium absorption in diverse populations and evaluation of unique aspects of mineral metabolism not accessible through other techniques. C1 TEXAS CHILDRENS HOSP, HOUSTON, TX 77030 USA. NICHHD, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. CREIGHTON UNIV, OMAHA, NE 68178 USA. RP ABRAMS, SA (reprint author), BAYLOR COLL MED, DEPT PEDIAT, USDA ARS, CHILDRENS NUTR RES CTR, 1100 BATES ST, HOUSTON, TX 77030 USA. OI Abrams, Steven/0000-0003-4972-9233 FU NIAMS NIH HHS [AR-07912] NR 28 TC 17 Z9 17 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 OCT PY 1994 VL 79 IS 4 BP 965 EP 969 DI 10.1210/jc.79.4.965 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200009 PM 7962306 ER PT J AU ARAI, K TSIGOS, C SUZUKI, Y IRONY, I KARL, M LISTWAK, S CHROUSOS, GP AF ARAI, K TSIGOS, C SUZUKI, Y IRONY, I KARL, M LISTWAK, S CHROUSOS, GP TI PHYSIOLOGICAL AND MOLECULAR ASPECTS OF MINERALOCORTICOID RECEPTOR ACTION IN PSEUDOHYPOALDOSTERONISM - A RESPONSIVENESS TEST AND THERAPY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-MYC GENE; GLUCOCORTICOID RESISTANCE; INHERITANCE; DEFICIENCY; UNRESPONSIVENESS; FAMILIES; DEFECTS; FORMS; DNA AB Pseudohypoaldosteronism (PHA), characterized by congenital resistance to aldosterone and excessive salt loss, has been traditionally treated with salt replacement. Although the mineralocorticoid receptor (MR) has been suggested as a potential locus of the defect in this disease, no such abnormality has been identified as yet. We studied a 17-yr-old male patient with congenital multifocal target organ resistance to aldosterone. Both carbenoxolone, an 11 beta-hydroxysteroid dehydrogenase inhibitor, and a high dose of fludrocortisone normalized the patient's serum electrolyte concentrations and decreased his urinary excretion of sodium, suggesting that this patient's resistance was partial and could be overcome by high concentrations of endogenous or exogenous mineralocorticoids. We hypothesized that the beneficial effect of these treatments was mostly mediated by the MR, because the administration of dexamethasone, while this patient was receiving a therapeutic dose of carbenoxolone, caused its reversal. These findings convinced us that there was functional, albeit possibly defective, MR in this patient and led us to perform molecular studies. Both alleles of the MR gene were expressed in the patient and his clinically and biochemically normal father. A conservative heterozygous mutation (A(760)-->G(760), Ileu(180)-->Va1(180)) and a nonconservative homozygous mutation (C-944-->T-944, Ala(241)-->Va1(241)) were identified in the complementary DNA of both the patient and his father. The first untranslated exon and 0.9 kilobase of the 5'-regulatory region were also identical in the two men. It appears that the mutations causing amino acid substitutions represent polymorphisms, as we found high frequencies of both in the general population. We conclude that carbenoxolone and fludrocortisone may help define the presence of functional MR in patients with PHA and that the former could be used in the long term therapy of this disease. We hypothesize that the defect causing PHA in this patient might be in a post-MR step of aldosterone action. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP ARAI, K (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 32 TC 45 Z9 45 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 OCT PY 1994 VL 79 IS 4 BP 1019 EP 1023 DI 10.1210/jc.79.4.1019 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200018 PM 7962269 ER PT J AU BACH, MA CHIN, E BONDY, CA AF BACH, MA CHIN, E BONDY, CA TI THE EFFECTS OF SUBCUTANEOUS INSULIN-LIKE GROWTH-FACTOR-I INFUSION IN INSULIN-DEPENDENT DIABETES-MELLITUS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FACTOR BINDING PROTEIN-1; AMINO-ACID-METABOLISM; IGF-I; FACTOR RECEPTOR; HORMONE LEVELS; GLUCOSE; RAT; ADOLESCENTS; SECRETION; HUMANS AB Insulin-dependent diabetes can be associated with low insulin-like growth factor-I(IGF-I) levels despite normal or even high GH secretion. The basis of the diabetic abnormalities in GH-IGF dynamics that contribute to insulin resistance and impaired fuel metabolism are not well understood. To further investigate these matters, this study evaluated baseline IGF system parameters and responses to recombinant human IGF-I in four diabetic adolescents and six pubertal stage-matched controls. Spontaneous overnight and arginine-stimulated GH secretion, insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20 mu g/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were not significantly different in the two groups, but IGF-I levels were significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased dramatically in diabetics and modestly in normal subjects in response to IGF-I infusion, but IGFBP-3 levels were not significantly altered. Spontaneous overnight and arginine-stimulated GH secretion were suppressed by about 50% in both groups after IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I, and insulin secretion was suppressed in normal subjects, with no evidence of a change in insulin half-life. Blood glucose remained stable in both groups throughout saline and IGF-I infusions, and no hypoglycemia or other adverse effect occurred during IGF-I infusions. Further studies are necessary to determine whether the addition of IGF-I to insulin replacement therapy may stably reduce the insulin requirement, maintain normal GH levels, and perhaps achieve better metabolic and anabolic balance in the treatment of insulin-dependent diabetes. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 37 TC 52 Z9 52 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 OCT PY 1994 VL 79 IS 4 BP 1040 EP 1045 DI 10.1210/jc.79.4.1040 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200021 PM 7525624 ER PT J AU MAGIAKOU, MA MASTORAKOS, G CHROUSOS, GP AF MAGIAKOU, MA MASTORAKOS, G CHROUSOS, GP TI FINAL STATURE IN PATIENTS WITH ENDOGENOUS CUSHINGS-SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE; DISEASE AB Growth retardation to complete growth arrest is the hallmark of Cushing's syndrome in children and growing adolescents; however, the effect of endogenous hypercortisolism on the final adult stature of these patients is not known. We examined this in 10 children and adolescents with endogenous Cushing's syndrome who were evaluated and successfully treated at the NIH Clinical Center before having completed their growth. The bone age was consistent with the chronological age or accelerated in four of six (67%) and delayed in two of six patients (33%). The pretreatment height of patients with Cushing's syndrome in SD units was -1.7 +/- 1.3 (mean +/- SD), the final adult height -1.3 +/- 0.9, and the midparental height was 0 +/- 0.8. All patients had a compromised final adult stature compared to their midparental height (162.8 +/- 9.0 vs. 171.7 +/- 6.3 cm; P < 0.05). The mean (midparental height - final adult height) +/- SD was 8.9 +/- 7.3 cm. The final adult height in both centimeters and so units was significantly lower than the midparental height (P < 0.05), whereas it did not differ significantly from the predicted heights by the Bayley-Pinneau and Roche-Wainer-Thissen methods. We conclude that the growth retardation caused during the hypercortisolemic state of Cushing's syndrome is associated with a compromised final adult height, possibly as a result of inadequate postcure catch-up growth. RP MAGIAKOU, MA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 22 TC 70 Z9 71 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 OCT PY 1994 VL 79 IS 4 BP 1082 EP 1085 DI 10.1210/jc.79.4.1082 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200028 PM 7962277 ER PT J AU ZHAO, Y CHEGINI, N FLANDERS, KC AF ZHAO, Y CHEGINI, N FLANDERS, KC TI HUMAN FALLOPIAN-TUBE EXPRESSES TRANSFORMING GROWTH-FACTOR (TGF-BETA) ISOFORMS, TGF-BETA TYPE I-III RECEPTOR MESSENGER-RIBONUCLEIC-ACID AND PROTEIN, AND CONTAINS [I-125] TGF-BETA-BINDING SITES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PERIIMPLANTATION PERIOD; CYCLIC CHANGES; MOUSE UTERUS; FACTOR-ALPHA; CELL HEIGHT; BINDING; CLONING; FACTOR-BETA-1; EPITHELIUM; RNA AB Reverse transcription-polymerase chain reaction analysis of total ribonucleic acid (RNA) from human fallopian tubes revealed that transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 as well as TGF beta type I-III messenger RNA (mRNA) are expressed in this tissue. In situ hybridization and immunohistochemical observations using TGF beta isoform-specific [S-35]40-mer oligonucleotide probes and polyclonal antibodies indicate that all the tubal cell types express TGF beta isoforms and TGF beta type II receptor mRNA and protein. The tubal epithelial cells appeared to express more TGF beta 1 mRNA and TGF beta 1-3 proteins than other cell types, whereas TGF beta 2 and TGF beta 3 mRNA appeared to be equally expressed in the epithelial and other tubal cell types, In the epithelial lining, both ciliated and nonciliated cells in the ampullary and isthmus regions appeared to express mRNA and protein for TGF beta s and TGF beta type II receptor at a similar level. The intensity of immunostaining of TGF beta s in tubal epithelial cells was lower during the early proliferative and late secretory than the mid- to late proliferative and early to midsecretory phases of the menstrual cycle and reduced during the postmenopausal period. However, the intensity of immunoreactive TGF beta type II receptor in these cells did not vary during the cycle as much as that seen with TGF beta s. Quantitative autoradiography of [I-125]TGF beta 1 indicates that fallopian tubes contain specific binding sites for TGF beta 1. Net grain density per 100 mu m(2), calculated for different cell types, indicates that the epithelial cells had a significantly higher grain density than other tubal cell types (P < 0.05), with similar densities in the late proliferative and early secretory phases of the cycle. These results provide the first evidence that human fallopian tubes express mRNA and protein and contain specific binding sites for TGF beta system, suggesting an autocrine/paracrine rob for TGF beta in a variety of tubal functions. C1 UNIV FLORIDA, DEPT OBSTET & GYNECOL, GAINESVILLE, FL 32610 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NR 41 TC 36 Z9 36 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 OCT PY 1994 VL 79 IS 4 BP 1177 EP 1184 DI 10.1210/jc.79.4.1177 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200046 PM 7962292 ER PT J AU MASTORAKOS, G SCOPA, CD VRYONIDOU, A FRIEDMAN, TC KATTIS, D PHENEKOS, C MERINO, MJ CHROUSOS, GP AF MASTORAKOS, G SCOPA, CD VRYONIDOU, A FRIEDMAN, TC KATTIS, D PHENEKOS, C MERINO, MJ CHROUSOS, GP TI PRESENCE OF IMMUNOREACTIVE CORTICOTROPIN-RELEASING HORMONE IN NORMAL AND POLYCYSTIC HUMAN OVARIES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RAT LEYDIG-CELLS; FACTOR RECEPTORS; INVITRO FERTILIZATION; BETA-ENDORPHIN; NERVOUS-SYSTEM; SPINAL-CORD; SECRETION; LOCALIZATION; TESTIS; BIOSYNTHESIS AB Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also present in human ovaries, we examined ovaries from normal women and patients with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutes. No IrCRH was present in oocytes of primordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent from the stroma or the sparsely present corpora lutes and was clearly detected in oocytes of primordial follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries was higher than that in polycystic ovaries (mean +/- so, 0.075 +/- 0.02 vs. 0.038 +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid samples collected from women undergoing ovarian hyperstimulation for assisted reproduction had low, but detectable, levels of IrCRH (mean +/- so, 4.975 +/- 1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH is present in normal human ovaries and follicular fluid, suggesting that this neuropeptide may play a regulatory role in one or more of the various functions of this gonad, such as ovulation and/or luteolysis, through its proinflammatory properties and/or its auto/paracrine regulation of:steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localization in primary oocytes of polycystic ovaries may he related to the increased androgen biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in women with the polycystic ovarian syndrome, respectively. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RED CROSS HOSP, DEPT ENDOCRINOL, ATHENS, GREECE. NR 46 TC 60 Z9 61 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1994 VL 79 IS 4 BP 1191 EP 1197 DI 10.1210/jc.79.4.1191 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200048 PM 7525629 ER PT J AU DIBISCEGLIE, AM SIMPSON, LH LOTZE, MT HOOFNAGLE, JH AF DIBISCEGLIE, AM SIMPSON, LH LOTZE, MT HOOFNAGLE, JH TI DEVELOPMENT OF HEPATOCELLULAR-CARCINOMA AMONG PATIENTS WITH CHRONIC LIVER-DISEASE DUE TO HEPATITIS-C VIRAL-INFECTION SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE HEPATOCELLULAR CARCINOMA; HEPATITIS B VIRUS; HEPATITIS C VIRUS; CIRRHOSIS ID NON-B-HEPATITIS; POST-TRANSFUSION HEPATITIS; POLYMERASE CHAIN-REACTION; CHRONIC NON-A; VIRUS-DNA; UNITED-STATES; FOLLOW-UP; ANTIBODIES; CIRRHOSIS; PREVALENCE AB Although chronic infection with hepatitis C (HCV) and B viruses (HBV) are important risk factors for hepatocellular carcinoma (HCC), their relative roles in causing liver cancer remain poorly defined, particularly in developed Western countries. Thirty-one patients with HCC seen at the Clinical Center of the National Institutes of Health between 1986 and 1992 were evaluated serologically for evidence of HBV and HCV infection: antibodies to HBV and HCV and hepatitis B surface antigen (HBsAg) were detected by conventional immunoassays, and HCV RNA and HBV DNA were detected by polymerase chain reaction (PCR). Serologic evidence of HBV infection was found in 18 patients (56%), 17 with antibodies, 16 with HBV DNA, and 14 with HBsAg. Evidence of HCV infection was found in 10 patients (32%), seven of whom also had HCV RNA. One patient had both anti-HCV and HBsAg. In comparison to patients with HBV-related HCC, those with HCV-related cancer were older and more likely to be white, to have been born in the United States, to have a history of parenteral exposure, and to have cirrhosis. In two patients in whom the course of hepatitis C could be traced from its onset, hepatocellular carcinoma developed after 5 years in one and after 9 years in another case. Thus chronic HCV infection is a common etiology of cirrhosis among United States patients with HCC, often as a late complication of intravenous drug abuse or blood transfusion. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RP DIBISCEGLIE, AM (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 9C 103B,BETHESDA,MD 20892, USA. NR 28 TC 70 Z9 71 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 1994 VL 19 IS 3 BP 222 EP 226 DI 10.1097/00004836-199410000-00011 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PH781 UT WOS:A1994PH78100010 PM 7528758 ER PT J AU WALSH, CE NIENHUIS, AW SAMULSKI, RJ BROWN, MG MILLER, JL YOUNG, NS LIU, JM AF WALSH, CE NIENHUIS, AW SAMULSKI, RJ BROWN, MG MILLER, JL YOUNG, NS LIU, JM TI PHENOTYPIC CORRECTION OF FANCONI-ANEMIA IN HUMAN HEMATOPOIETIC-CELLS WITH A RECOMBINANT ADENOASSOCIATED VIRUS VECTOR SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GENE THERAPY; TRANSDUCTION; DNA REPAIR; HEMATOPOIESIS ID HUMAN GAMMA-GLOBIN; GROUP-C GENE; ADENOASSOCIATED VIRUS; CHROMOSOME BREAKAGE; PROGENITOR CELLS; INVITRO; CYCLE; INTEGRATION; FACC; DNA AB Fanconi anemia (FA) is a recessive inherited disease characterized by defective DNA repair. FA cells are hypersensitive to DNA cross-linking agents that cause chromosomal instability and cell death. FA is manifested clinically by progressive pancytopenia, variable physical anomalies, and predisposition to malignancy. Four complementation groups have been identified, termed A, B, C, and D. The gene for the FA complementation group C, FACC, has been cloned. Expression of the FACC cDNA corrects the phenotypic defect of FA(C) cells, resulting in normalized cell growth in the presence of DNA cross-linking agents such as mitomycin C (MMC). Gene transfer of the FACC gene should provide a survival advantage to transduced hematopoietic cells, suggesting that FA might be an ideal candidate for gene therapy. We demonstrated efficient transduction, expression, and phenotypic correction in lymphoblastoid cell lines derived from FA(C) patients using a recombinant adeno-associated virus (rAAV) vector containing the FACC gene. Molecular characterization of the transduced FACC gene showed an intact unrearranged proviral genome with expression sufficient to normalize cell growth, cell cycle kinetics and chromosomal breakage in the presence of MMC. These observations were extended by testing rAAV transduction in hematopoietic progenitor cells. Peripheral blood CD34(+) cells isolated from a FA(C) patient and transduced with rAAV/FACC virus yielded 5-10-fold more progenitor colonies than mock-infected cells, consistent with genetic ''rescue'' of corrected cells. This is the first demonstration of rAAV gene correction in primary human hematopoietic progenitor cells and has important implications for gene therapy of hematopoietic disorders, specifically FA. C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38112 USA. UNIV N CAROLINA, DEPT PHARMACOL, CHAPEL HILL, NC 27599 USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. RP WALSH, CE (reprint author), NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. NR 47 TC 135 Z9 136 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 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1994 VL 94 IS 4 BP 1440 EP 1448 DI 10.1172/JCI117481 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PK185 UT WOS:A1994PK18500015 PM 7929819 ER PT J AU RIZZO, LV MILLERRIVERO, NE CHAN, CC WIGGERT, B NUSSENBLATT, RB CASPI, RR AF RIZZO, LV MILLERRIVERO, NE CHAN, CC WIGGERT, B NUSSENBLATT, RB CASPI, RR TI INTERLEUKIN-2 TREATMENT POTENTIATES INDUCTION OF ORAL TOLERANCE IN A MURINE MODEL OF AUTOIMMUNITY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AUTOIMMUNE DISEASE; UVEITIS; THERAPY; IMMUNOMODULATION; CYTOKINES ID MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; UVEORETINITIS; ENCEPHALOMYELITIS; TOLERIZATION; ANTIGENS; ANERGY AB The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3X regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) resulted in disease suppression that was equal to that of the protective 5X regimen. The protective effect was maintained across a range of IL-2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3X-fed and IL-2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3X regimen and to animals given the protective 5X regimen. We propose that IL-2 treatment enhances protection from EAU at least in part by stimulating production of antiinflammatory cytokines by regulatory cells in Payer's Patches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3X + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5X regimen might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe and effective way of potentiating oral tolerance. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 NR 17 TC 94 Z9 97 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1994 VL 94 IS 4 BP 1668 EP 1672 DI 10.1172/JCI117511 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PK185 UT WOS:A1994PK18500045 PM 7929845 ER PT J AU DROMER, F VARMA, A RONIN, O MATHOULIN, S DUPONT, B AF DROMER, F VARMA, A RONIN, O MATHOULIN, S DUPONT, B TI MOLECULAR TYPING OF CRYPTOCOCCUS-NEOFORMANS SEROTYPE-D CLINICAL ISOLATES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; CAPSULAR POLYSACCHARIDE; EPIDEMIOLOGIC DIFFERENCES; MONOCLONAL-ANTIBODIES; AIDS; DNA; MENINGITIS; VIRULENCE; STRAINS AB Cryptococcus neoformans serotype A is responsible for the majority of cryptococcal infections in AIDS patients. In France, approximately 17% of the patients are infected with serotype D, regardless of their human immunodeficiency virus status. In a retrospective study of 273 patients, we found that serotype D was unevenly distributed in France. We wondered if this was related to the yeast's genetic background. We used karyotyping and DNA fingerprints generated by UT-4p to analyze 40 serotype D clinical isolates. We found an extensive polymorphism, with only two conserved karyotypes from drug-addicted patients living in the same area. Although highly variable, the DNA fingerprints were classified into 10 groups. Four pairs of isolates were identical; three of these pairs were from patients living in the same area, but there was no other correlation with the geographical area. The two isolates with identical karyotypes belonged to the same fingerprint group. Five of the six isolates that made up fingerprint group I were recovered from drug-addicted patients (P < 0.002; chi-square), and all five isolates found in fingerprint group III were from male homosexual patients (P < 0.02). Finally, five of the seven isolates from patients with cryptococcal pneumonia, were classified as fingerprint group V (P < 0.04). These results suggest that there are possible relationships between characteristics of the isolates and body localization or even risk factors. Results of the present study warrant other studies on isolates of all serotypes and on isolates from clinical and environmental sources. C1 NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892. RP DROMER, F (reprint author), INST PASTEUR,UNITE MYCOL,25 RUE DR ROUX,F-75724 PARIS 15,FRANCE. NR 32 TC 57 Z9 57 U1 1 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 OCT PY 1994 VL 32 IS 10 BP 2364 EP 2371 PG 8 WC Microbiology SC Microbiology GA PG912 UT WOS:A1994PG91200005 PM 7814467 ER PT J AU IHDE, DC MULSHINE, JL KRAMER, BS STEINBERG, SM LINNOILA, RI GAZDAR, AF EDISON, M PHELPS, RM LESAR, M PHARES, JC GRAYSON, J MINNA, JD JOHNSON, BE AF IHDE, DC MULSHINE, JL KRAMER, BS STEINBERG, SM LINNOILA, RI GAZDAR, AF EDISON, M PHELPS, RM LESAR, M PHARES, JC GRAYSON, J MINNA, JD JOHNSON, BE TI PROSPECTIVE RANDOMIZED COMPARISON OF HIGH-DOSE AND STANDARD-DOSE ETOPOSIDE AND CISPLATIN CHEMOTHERAPY IN PATIENTS WITH EXTENSIVE-STAGE SMALL-CELL LUNG-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTENSIVE INDUCTION CHEMOTHERAPY; METASTATIC BREAST-CANCER; SOUTHWEST-ONCOLOGY-GROUP; PHASE-III TRIAL; BRONCHOGENIC-CARCINOMA; COMBINATION CHEMOTHERAPY; PROGNOSTIC FACTORS; CLINICAL-TRIAL; DOSAGE SCHEDULES; CYCLOPHOSPHAMIDE AB Purpose: We performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients. Patients and Methods: Ninety patients with previously untreated extensive-stage SCLC: fulfilled criteria for randomization to standard dose versus high-dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m(2) on days 1 to 3 and cisplatin 80 mg/m(2) on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m(2) on days 1 to 5 and cisplatin 27 mg/m(2) on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor-cell lines established from individual patients. Results: Despite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to chose randomised to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P < .0001), thrombocytopenia (P < .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP. Conclusion: No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities. C1 NCI, USN, MED ONCOL BRANCH, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD USA. NATL NAVAL MED CTR, DEPT MED, BETHESDA, MD USA. UNIFORMED SERV UNIV HLTH SCI, DEPT RADIOL, BETHESDA, MD USA. NR 68 TC 206 Z9 209 U1 1 U2 6 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 OCT PY 1994 VL 12 IS 10 BP 2022 EP 2034 PG 13 WC Oncology SC Oncology GA PL363 UT WOS:A1994PL36300005 PM 7931470 ER PT J AU FOSS, FM IHDE, DC LINNOILA, IR FISCHMANN, AB SCHECHTER, GP COTELINGAM, JD STEINBERG, SM GHOSH, BC STOCKER, JL BASTIAN, A PHARES, JC SAUSVILLE, EA AF FOSS, FM IHDE, DC LINNOILA, IR FISCHMANN, AB SCHECHTER, GP COTELINGAM, JD STEINBERG, SM GHOSH, BC STOCKER, JL BASTIAN, A PHARES, JC SAUSVILLE, EA TI PHASE-II TRIAL OF FLUDARABINE PHOSPHATE AND INTERFERON ALFA-2A IN ADVANCED MYCOSIS-FUNGOIDES SEZARY-SYNDROME SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID T-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; LEUKOCYTE-A-INTERFERON; NON-HODGKINS-LYMPHOMA; LOW-GRADE LYMPHOMA; SEZARY-SYNDROME; RECOMBINANT INTERFERON; CLINICOPATHOLOGIC ENTITY; THERAPY; PENTOSTATIN AB Purpose: This phase It study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sezary syndrome (SS). Patients and Methods: Thirty-five patients were treated with fludarabine 25 mg/m(2) intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m(2) subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/ m(2) at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients herd not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. Results: Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes tester, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis. Conclusion: The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD. NCI,NATL NAVAL MED CTR,BETHESDA,MD. GEORGE WASHINGTON UNIV,WASHINGTON,DC. VET AFFAIRS MED CTR,WASHINGTON,DC. NR 54 TC 69 Z9 69 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 OCT PY 1994 VL 12 IS 10 BP 2051 EP 2059 PG 9 WC Oncology SC Oncology GA PL363 UT WOS:A1994PL36300008 PM 7931473 ER PT J AU LONGO, DL DUFFEY, PL JAFFE, ES RAFFELD, M HUBBARD, SM FISHER, RI WITTES, RE DEVITA, VT YOUNG, RC AF LONGO, DL DUFFEY, PL JAFFE, ES RAFFELD, M HUBBARD, SM FISHER, RI WITTES, RE DEVITA, VT YOUNG, RC TI DIFFUSE SMALL NONCLEAVED-CELL, NON-BURKITTS LYMPHOMA IN ADULTS - A HIGH-GRADE LYMPHOMA RESPONSIVE TO PROMACE-BASED COMBINATION CHEMOTHERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; AGGRESSIVE LYMPHOMAS; MALIGNANT-LYMPHOMA; UNITED-STATES; FEATURES; THERAPY; PROGNOSIS; VARIANTS; CHILDREN; REGIMEN AB Purpose: To review the efficacy of cyclophosphamide, doxorubicin, etoposide, methotrexate with leucovorin, and prednisone (ProMACE)-based combination chemotherapy programs in the treatment of patients with diffuse small noncleaved-cell non-Burkitt's lymphoma. Patients and Methods: Thirty-three patients with diffuse smell noncleaved;cell non-Burkitt's lymphoma were accrued: eight with localized disease were treated with modified ProMACE-mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin, vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median follow-up duration is 10 years. Results: All eight patients with localized disease achieved a complete response, none have relapsed, and one died of intercurrent illness. Among patients with advanced-stage disease, five of eight (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a complete response. If the two ProMACE-MOPP-based groups are considered together, disease-free and overall survival rates at 15 years are projected at 61% and 35%, respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM-induced complete remission, and overall survival of ProMACE-CytaBOM-treated patients (88%) is significantly higher than that for flexitherapy and proMACE-MOPP (P-2 = .04). Conclusion: Adult patients with diffuse small noncleaved-cell non-burkitts lymphoma may be effectively treated with regimens that are effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma). C1 NCI,DIV CANC TREATMENT,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,CTR INT CANC INFORMAT,BETHESDA,MD. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. LOYOLA UNIV,STRITCH SCH MED,MAYWOOD,IL 60153. YALE UNIV,SCH MED,NEW HAVEN,CT. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RP LONGO, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 576,FREDERICK,MD 21702, USA. NR 25 TC 31 Z9 31 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1994 VL 12 IS 10 BP 2153 EP 2159 PG 7 WC Oncology SC Oncology GA PL363 UT WOS:A1994PL36300022 PM 7523607 ER PT J AU CHESON, BD VENA, DA FOSS, FM SORENSEN, JM AF CHESON, BD VENA, DA FOSS, FM SORENSEN, JM TI NEUROTOXICITY OF PURINE ANALOGS - A REVIEW SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; PHASE-II TRIAL; CONTINUOUS-INFUSION SCHEDULE; ACUTE LYMPHOBLASTIC-LEUKEMIA; NERVOUS-SYSTEM TOXICITY; FLUDARABINE PHOSPHATE; PROLYMPHOCYTIC LEUKEMIA; EUROPEAN ORGANIZATION; PEDIATRIC-PATIENTS AB Purpose: The purine analogs, fludarabine, cladribine, and pentostatin, are active against a broad spectrum of indolent lymphoid malignancies. They also have similar toxicities, including myelosuppression, immunosuppression, and sporadic neurotoxicity. This review compares the spectrum of neurotoxicity of each of these agents. Now that these drugs are commercially available and are being widely used, physicians should be aware of potentially serious side effects that may be encountered. Methods: The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the fail of 1993. In addition, case records from National Cancer Institute (NCI) Group C protocols were reviewed for fludarabine in chronic lymphocytic leukemia (CLL), and cladribine and pentostatin in hairy cell leukemia (HCL), as well as adverse drug reactions reported to the NCI from January 1980 through September 1993. Results: At higher than recommended doses, life-threatening and fatal neurotoxicity were encountered with all three drugs. At the recommended doses, each agent induced neurotoxicity in approximately 15% of patients, mostly mild and reversible. However, severe neurologic complications were reported; these were occasionally delayed, sometimes fatal, but often at least partially reversible. Conclusion: The doses of these three agents should not be increased above the recommended levels. Development of moderate or worse neurotoxicity should result in discontinuation of that drug. (C) 1994 by American Society of Clinical Oncology. C1 EMMES CORP,POTOMAC,MD. BOSTON UNIV,MED CTR,MED ONCOL SECT,BOSTON,MA. RP CHESON, BD (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,ROOM 741,BETHESDA,MD 20892, USA. NR 89 TC 125 Z9 127 U1 0 U2 2 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 OCT PY 1994 VL 12 IS 10 BP 2216 EP 2228 PG 13 WC Oncology SC Oncology GA PL363 UT WOS:A1994PL36300030 PM 7931492 ER PT J AU PIGOTT, TA LHEUREUX, F DUBBERT, B BERNSTEIN, S MURPHY, DL AF PIGOTT, TA LHEUREUX, F DUBBERT, B BERNSTEIN, S MURPHY, DL TI OBSESSIVE-COMPULSIVE DISORDER - COMORBID CONDITIONS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on New Developments in the Treatment of OCD CY APR 15, 1994 CL MCLEAN, VA ID BODY-DYSMORPHIC DISORDER; SEROTONIN REUPTAKE INHIBITORS; LA-TOURETTES SYNDROME; 7-YEAR FOLLOW-UP; ANOREXIA-NERVOSA; PANIC DISORDER; PERSONALITY-DISORDERS; BULIMIA-NERVOSA; M-CHLOROPHENYLPIPERAZINE; CLOMIPRAMINE TREATMENT AB According to DSM-IV criteria, obsessive compulsive disorder (OCD) is an anxiety disorder that is characterized by recurrent, intrusive images or thoughts and/or stereotyped, repetitive behaviors that are associated with marked distress, anxiety, or psychosocial impairment. The differential diagnosis of OCD can be quite difficult since OCD symptomatology can occur as either primary or secondary phenomena. Comorbid depression or personality disorder is not uncommon in patients with primary OCD. Other comorbid conditions that occur with OCD can be divided into three major groups based on core features: (1) disorders of altered risk assessment; (2) incompleteness/habit-spectrum disorders; and (3) psychotic spectrum disorders. Such a categorization of core dimensions and comorbid conditions may prove useful in identifying distinct OCD subtypes that share underlying neurobiological or treatment response characteristics. C1 MCGILL UNIV,MONTREAL,PQ H3A 2T5,CANADA. NIMH,CLIN SCI LAB,ROCKVILLE,MD 20857. RP PIGOTT, TA (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,DIV PSYCHOPHARMACOL RES,KOBER COGAN BLDG,6TH FLOOR,WASHINGTON,DC 20007, USA. NR 144 TC 96 Z9 100 U1 4 U2 10 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1994 VL 55 SU S BP 15 EP 32 PG 18 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PW789 UT WOS:A1994PW78900003 PM 7961529 ER PT J AU DANIEL, DG RANDOLPH, C JASKIW, G HANDEL, S WILLIAMS, T ABI-DARGHAM, A SHOAF, S EGAN, M ELKASHEF, A LIBOFF, S LINNOILA, M AF DANIEL, DG RANDOLPH, C JASKIW, G HANDEL, S WILLIAMS, T ABI-DARGHAM, A SHOAF, S EGAN, M ELKASHEF, A LIBOFF, S LINNOILA, M TI COADMINISTRATION OF FLUVOXAMINE INCREASES SERUM CONCENTRATIONS OF HALOPERIDOL SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID FLUOXETINE; SCHIZOPHRENIA; SYMPTOMS; MALEATE AB Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine. C1 NIMH, NEUROSCI CTR ST ELIZABETHS, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NIMH, NEUROSCI CTR ST ELIZABETHS, DEPT INTRAMURAL RES, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA. NIAAA, BETHESDA, MD USA. RP DANIEL, DG (reprint author), WASHINGTON CLIN RES CTR, 6404-P 7 CORNERS PL, FALLS CHURCH, VA 22044 USA. NR 28 TC 88 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 1994 VL 14 IS 5 BP 340 EP 343 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA PH784 UT WOS:A1994PH78400009 PM 7806690 ER PT J AU LAMB, ME AF LAMB, ME TI THE PARENT-INFANT BONDING CONTROVERSY - A CRITIQUE OF THE CRITICS - RESPONSE SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Note ID CONTACT RP LAMB, ME (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 1994 VL 15 IS 5 BP 384 EP 385 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA PL688 UT WOS:A1994PL68800011 ER PT J AU GIACCHETTI, G FALOIA, E TACCALITI, A MOROSINI, PP ARNALDI, G SOLETTI, F MANTERO, F ACCILI, D DEPIRRO, R AF GIACCHETTI, G FALOIA, E TACCALITI, A MOROSINI, PP ARNALDI, G SOLETTI, F MANTERO, F ACCILI, D DEPIRRO, R TI DECREASED EXPRESSION OF INSULIN-SENSITIVE GLUCOSE-TRANSPORTER MESSENGER-RNA (GLUT-4) IN ADIPOSE-TISSUE OF NON-INSULIN-DEPENDENT DIABETIC AND OBESE PATIENTS - EVALUATION BY A SIMPLIFIED QUANTITATIVE PCR ASSAY SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE GLUCOSE-TRANSPORTER INSULIN-RESISTANCE; NON-INSULIN-DEPENDENT DIABETES; ADIPOSE TISSUE ID POLYMERASE CHAIN-REACTION; SKELETAL-MUSCLE; GENE-EXPRESSION; MESSENGER-RNA; NIDDM; RECEPTOR; RESISTANCE; MELLITUS; DEFECT AB Impaired cellular uptake and utilization of glucose is the hallmark of non-insulin-dependent-diabetes (NIDDM). We have developed a quantitative assay to probe the expression of glucose-transporter genes in tissues derived from patients with NIDDM. Using the polymerase chain reaction (PCR), we assessed levels of expression of the insulin responsive glucose transporter GLUT-4 in adipose tissue of patients with NIDDM and in obese patients. We report that expression of GLUT-4 is reduced in NIDDM and in obesity associated with hyperinsulinemia and insulin resistance. These results suggest that reduction of GLUT-4 levels in the adipose cell plays an important role in the pathogenesis of insulin resistance, an early feature of NIDDM. C1 UNIV ANCONA,SCH MED,ENDOCRINOL CLIN,ANCONA,ITALY. OSPED CIVILE C & G MAZZONI,ASCOLI PICENO,ITALY. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 21 TC 14 Z9 15 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 1994 VL 17 IS 9 BP 709 EP 715 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PQ796 UT WOS:A1994PQ79600004 PM 7868815 ER PT J AU WIEST, DL KEARSE, KP SHORES, EW SINGER, A AF WIEST, DL KEARSE, KP SHORES, EW SINGER, A TI DEVELOPMENTALLY-REGULATED EXPRESSION OF CD3 COMPONENTS INDEPENDENT OF CLONOTYPIC T-CELL ANTIGEN RECEPTOR COMPLEXES ON IMMATURE THYMOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODY; CD4+CD8+ THYMOCYTES; SCID MICE; SURFACE EXPRESSION; TYROSINE KINASE; DELTA-CHAIN; BETA-CHAIN; PROTEINS; TCR; IDENTIFICATION AB CD3 signal transducing proteins are thought to be expressed on the surface of T cells only as part of clonotypic T cell receptor (TCR) complexes. Contrary to this paradigm, the present study describes surface expression of CD3 proteins independently of clonotypic TCR complexes, but only on immature thymocytes. Such novel clonotype-independent CD3 (CIC) complexes are composed primarily of CD3 gamma epsilon and secondarily of CD3 delta epsilon heterodimers that are independent of one another and are expressed on the cell surface in association with an unknown 90-100 kD protein termed CD3-associated protein (CD3AP). CIC complexes are expressed in normal mice on early thymocytes through the CD4(+)CD8(+) stage of development, but not on mature peripheral T cells. Furthermore, CIC complexes are expressed by both TCR(-) severe combined immunodeficiency (SCID) thymocytes and thymoma cell lines, in the absence of any clonotypic chains. The isolation and biochemical characterization of surface CIC complexes provides a structural basis for the signaling effects of anti-CD3 epsilon antibody treatment in early thymocyte development. RP WIEST, DL (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Wiest, David/0000-0002-0792-3188 NR 36 TC 51 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1375 EP 1382 DI 10.1084/jem.180.4.1375 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300021 PM 7931071 ER PT J AU ZHAO, TM WHITAKER, SE ROBINSON, MA AF ZHAO, TM WHITAKER, SE ROBINSON, MA TI A GENETICALLY-DETERMINED INSERTION/DELETION RELATED POLYMORPHISM IN HUMAN T-CELL RECEPTOR-BETA CHAIN (TCRB) INCLUDES FUNCTIONAL VARIABLE GENE SEGMENTS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; V-BETA; ANTIGEN RECEPTOR; REGION GENES; HUMAN FAMILIES; MOUSE STRAIN; RECOMBINATION; ORGANIZATION; POPULATIONS; DELETION AB Polymorphism in the human T cell receptor beta chain (TCRB) gene complex includes haplotypes with different numbers of TCRBV genes. An insertion/deletion related polymorphism (IDRP) in the human TCRBV region was found to involve TCRBV gene segments. Inserted TCRB haplotypes contain an additional 21.5 kb in which three TCRBV genes are encoded, members of the TCRBV7, TCRBV9, and TCRBV13 families. Two TCRBV gene segments were present only in inserted haplotypes; one of these, TCRBV7S3, is a functional gene and the other, TCRBV9S2(P), is a pseudogene because of an inframe termination colon. In addition, inserted haplotypes contain two identical copies of the TCRBV13S2 gene, whereas deleted haplotypes have only one copy. Deleted haplotypes could be subdivided into two types, deleted*1 and deleted*2, on the basis of sequence variations in TCRBV6S7 and TCRBV13S2 genes. Both deleted*1 and deleted*2 haplotypes contained the same number of TCRBV genes; both contain 60 genes of which 50 are functional, whereas, inserted haplotypes contained 63 genes of which 52 are functional. Comparisons of inserted region sequences with the homologous region in a deleted haplotype, and with sequences surrounding related TCRBV genes, revealed patterns of similarity that suggest insertion as well as deletion events have occurred in the evolution of the TCRBV gene complex. These data indicate that the genomic TCR repertoire is expanded in individuals who have inserted TCRBV haplotypes. The presence of additional TCRBV genes or, alternatively the absence of certain TCRBV genes may have an impact upon immune responses and susceptibility to autoimmune diseases. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 38 TC 33 Z9 35 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1405 EP 1414 DI 10.1084/jem.180.4.1405 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300024 PM 7931073 ER PT J AU FRANZOSO, G BISWAS, P POLI, G CARLSON, LM BROWN, KD TOMITAYAMAGUCHI, M FAUCI, AS SIEBENLIST, UK AF FRANZOSO, G BISWAS, P POLI, G CARLSON, LM BROWN, KD TOMITAYAMAGUCHI, M FAUCI, AS SIEBENLIST, UK TI A FAMILY OF SERINE PROTEASES EXPRESSED EXCLUSIVELY IN MYELO-MONOCYTIC CELLS SPECIFICALLY PROCESSES THE NUCLEAR FACTOR-KAPPA-B SUBUNIT P65 IN-VITRO AND MAY IMPAIR HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN THESE CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN NEUTROPHIL ELASTASE; HUMAN CATHEPSIN-G; MONONUCLEAR PHAGOCYTES; ONCOPROTEIN BCL-3; POLYMORPHONUCLEAR LEUKOCYTES; TRANSCRIPTIONAL ACTIVATOR; DIFFERENTIATING AGENTS; MOLECULAR-CLONING; LANGERHANS CELLS; TYPE-1 INFECTION AB Two groups of U937 promonocytic cells were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 (HIV-1) replication. ''Plus'' clones replicated the virus efficiently, whereas ''minus'' clones did not. We examined these clones for differences in nuclear factor (NF)-kappa B activity which might account for the observed phenomenon. Stimulation of plus clones liberated the classical p50-p65 complex from cytoplasmic pools, whereas minus clones produced an apparently novel, faster-migrating complex, as judged by electrophoretic mobility shift assays. It is surprising that the faster-migrating complex was composed also of p50 and p65. However, the p65 subunit was COOH-terminally truncated, as shown by immunoprecipitation. The truncation resulted from limited proteolysis of p65 during cellular extraction which released particular lysosomal serine proteases, such as elastase, cathepsin G, and proteinase 3. These specific proteases are coordinately expressed and were present exclusively in the minus U937 clones, but not in the plus clones, as demonstrated in the case of cathepsin G. In addition, these proteases were detected in certain subclones of THP-1 and HL-60 cells and in primary monocytes, in each case correlating with the truncated form of p65. We demonstrate in vitro cleavage of p65 by purified elastase and cathepsin G. It is possible that particular serine proteases may have inhibiting effects on the replication of HIV-1 in myelo-monocytic cells. The data also demonstrate that special precautions must be taken when making extracts from myelomonocytic cells. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 77 TC 84 Z9 84 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1445 EP 1456 DI 10.1084/jem.180.4.1445 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300028 PM 7931077 ER PT J AU CHEN, WS KHILKO, S FECONDO, J MARGULIES, DH MCCLUSKEY, J AF CHEN, WS KHILKO, S FECONDO, J MARGULIES, DH MCCLUSKEY, J TI DETERMINANT SELECTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED ANTIGENIC PEPTIDES IS EXPLAINED BY CLASS I-PEPTIDE AFFINITY AND IS STRONGLY INFLUENCED BY NONDOMINANT ANCHOR RESIDUES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MHC CLASS-I; T-CELL RECEPTOR; SURFACE-PLASMON RESONANCE; TOXIC LYMPHOCYTES-T; SELF-PEPTIDES; ENDOPLASMIC-RETICULUM; SOLUBLE-PROTEIN; BINDING GROOVE; GENE-PRODUCTS; HLA MOLECULES AB The contribution of major histocompatibility complex (MHC) class I-peptide affinity to immunodominance of particular peptide antigens (Ags) in the class I-restricted cytotoxic T lymphocyte (CTL) response is not clearly established. Therefore, we have compared the H-2K(b)-restricted binding and presentation of the immunodominant ovalbumin (OVA)(257-264) (SIINFEKL) determinant to that of a subdominant OVA determinant OVA(55-62) (KVVRFDKL). Immuno-dominance of OVA(257-264) was not attributable to the specific T cell repertoire but correlated instead with more efficient Ag presentation. This enhanced Ag presentation could be accounted for by the higher affinity of K-b/OVA(257-264) compared with K-b/OVA(55-62) despite the presence of a conserved K-b-binding motif in both peptides. Kinetic binding studies using purified soluble H-2K(b) molecules (K-s(b)) and biosensor techniques indicated that the K-on for association of OVA(257-264-C6) and K-s(b) at 25 degrees C was similar to 10-fold faster (5.9 x 10(3) M(-1) s(-1) versus 6.5 x 10(2) M(-1) s(-1)), and the K-off approximately twofold slower (9.1 x 10(-6) s(-1) versus 1.6 x 10(-5) s(-1)), than the rate constants for interaction of OVA(55-62-C6) and K-s(b). The association of these peptides with K-b was significantly influenced by multiple residues at presumed nonanchor sites within the peptide sequence. The contribution of each peptide residue to K-b-binding was dependent upon the sequence context and the summed contributions were not additive. Thus the affinity of MHC class I-peptide binding is a critical factor controlling presentation of peptide Ag and immunodominance in the class I-restricted CTL response. C1 FLINDERS UNIV S AUSTRALIA,MED CTR,CTR TRANSFUS MED & IMMUNOL,BEDFORD PK,SA 5042,AUSTRALIA. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. SWINBURNE UNIV TEHCNOL,DEPT APPL CHEM,HAWTHORN,VIC 3122,AUSTRALIA. RI Chen, Weisan/E-7828-2012; Margulies, David/H-7089-2013; McCluskey, James/A-1291-2007; OI McCluskey, James/0000-0002-8597-815X; Margulies, David/0000-0001-8530-7375 NR 70 TC 196 Z9 198 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1471 EP 1483 DI 10.1084/jem.180.4.1471 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300030 PM 7523572 ER PT J AU ZUNIGAPFLUCKER, JC JIANG, D SCHWARTZBERG, PL LENARDO, MJ AF ZUNIGAPFLUCKER, JC JIANG, D SCHWARTZBERG, PL LENARDO, MJ TI SUBLETHAL GAMMA-RADIATION INDUCES DIFFERENTIATION OF CD4-/CD8- INTO CD4+/CD8+ THYMOCYTES WITHOUT T-CELL RECEPTOR-BETA REARRANGEMENT IN RECOMBINASE ACTIVATION GENE 2-/- MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID RESTORATION; IRRADIATION; EXPRESSION; MUTATIONS; MOUSE AB DNA recombination of the immunoglobulin (Ig) or T cell receptor (TCR) gene loci is an essential step in the production of lymphocytes bearing antigen-specific receptors. Mice that lack the ability to rearrange their Ig and TCR gene loci are devoid of mature B and T cells. Complete rearrangement and expression of the TCR-beta chain has been suggested to allow immature thymocytes to switch from the CD4(-)/CD8(-) to the CD4(+)/CD8(+) stage of thymic development. Thus, thymocytes from severe combined immune deficient (SCID) mice or mice deficient in recombinase activation genes (RAG), which do not undergo proper DNA rearrangement, are arrested at the early CD4(-)/CD8(-) stage of development. B cell precursors in SCID or RAG mice do not progress from the B220(+)/sIgM(-)/heat stable antigen (HSA)(+)/CD43(+) to the B220(+)/sIgM(-)/HSA(+)/ CD43(-) stage. In an attempt to reconstitute RAG-2-/- mice with bone marrow- or fetal liver-derived progenitor cells, we subjected these mice to sublethal doses of gamma-radiation. It is surprising that in the absence of donor cells, irradiated RAG-2-/- mice revealed a dramatic change in their lymphoid phenotype. 14 d after irradiation, the majority of thymocytes had advanced to the CD4(+)/CD8(+) stage of T cell development and a small number of bone marrow precursors had progressed to the CD43(-), HSA(hi) stage of B cell development. Analysis of the resulting CD4(+)/CD8(+) thymocytes revealed no surface expression of the TCR/CD3 complex and no V-D-J rearrangement of the TCR-beta gene locus. Our findings provide evidence for a novel pathway that allows the transition of thymocytes from the CD4(-)/CD8(-) to the CD4(+)/CD8(+) stage and that does not appear to require TCR-beta chain rearrangement. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Zuniga-Pflucker, Juan/H-1295-2012; OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 NR 23 TC 52 Z9 52 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1517 EP 1521 DI 10.1084/jem.180.4.1517 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300034 PM 7931082 ER PT J AU RELLAHAN, BL JENSEN, JP WEISSMAN, AM AF RELLAHAN, BL JENSEN, JP WEISSMAN, AM TI TRANSCRIPTIONAL REGULATION OF THE T-CELL ANTIGEN RECEPTOR ZETA-SUBUNIT - IDENTIFICATION OF A TISSUE-RESTRICTED PROMOTER SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID NATURAL-KILLER-CELLS; ETS GENE FAMILY; CHAIN GENE; COMPLEX; EXPRESSION; ENHANCER; FC; DEGRADATION; LYMPHOCYTES; SPECIFICITY AB The cell surface expression of T cell antigen receptors (TCR) is regulated in part by the limiting synthesis of the zeta subunit. Utilizing fragments from the 5' region of the human zeta gene, two discrete regions that promote transcription were characterized. Both of these elements are located within 125 bases of the most 3' site of transcription initiation. The more proximal (3') promoter exhibits activity in lymphoid as well as nonlymphoid cells. In contrast, the more distal (5') promoter element functions in a tissue-restricted fashion. The tissue-specific promoter is localized to a 29-base fragment. The sequence of this region is remarkable for a stretch of 11 consecutive purines that are required for activity. This element constitutes the only known tissue-specific promoter for an invariant TCR subunit. Consistent with the unique role served by the zeta subunit in assembly of the TCR, this study demonstrates that the expression of the zeta gene is regulated in a fashion distinct from other TCR components. C1 NCI,IMMUNE CELL BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. NR 43 TC 30 Z9 31 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1529 EP 1534 DI 10.1084/jem.180.4.1529 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300036 PM 7931084 ER PT J AU SMITH, PD FOX, CH MASUR, H WINTER, HS ALLING, DW AF SMITH, PD FOX, CH MASUR, H WINTER, HS ALLING, DW TI QUANTITATIVE-ANALYSIS OF MONONUCLEAR-CELLS EXPRESSING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNA IN ESOPHAGEAL MUCOSA SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD; INFECTED-CELLS; AIDS; LIPOPOLYSACCHARIDE; MACROPHAGES; DISEASE; HIV-1; LYMPHOCYTES; REPLICATION AB The mucosa of the gastrointestinal tract is presumably an important reservoir for human immunodeficiency virus type 1 (HIV-1), but the level of virus-expressing cells within the mucosa of infected patients is not known. To study this issue, we identified HIV-1 mRNA-expressing (positive) mononuclear cells by in situ hybridization in specimens of esophageal mucosa from eight patients with acquired immune deficiency syndrome (AIDS) and esophageal infections. Such cells were not found in four patients with AIDS and no esophageal disease. Immunocytochemical staining revealed that the mononuclear cells expressing HIV-1 mRNA were lamina propria macrophages. The prevalence of positive cells was measured by triplicate determinations in each of three experiments using an inverse sampling technique. No significant differences in prevalence were found among patients or among experiments. The overall prevalence of HIV-1 mRNA-expressing cells in the esophageal lamina propria was 0.059 +/- 0.01%. This prevalence of cells expressing HIV-1 mRNA in the mucosa of patients with mucosal infections may reflect the local abundance of stimuli such as bacterial endotoxin and certain cytokines capable of inducing viral transcription. C1 MOLEC HISTOL LABS,GAITHERSBURG,MD 20879. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,OFF INTRAMURAL DIRECTOR,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02118. RP SMITH, PD (reprint author), UNIV ALABAMA,SCH MED,DEPT MED,DIV GASTROENTEROL,UAB STN,BIRMINGHAM,AL 35294, USA. FU NIDDK NIH HHS [DK-47322] NR 31 TC 50 Z9 50 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1541 EP 1546 DI 10.1084/jem.180.4.1541 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300038 PM 7931086 ER PT J AU SERREZE, DV PROCHAZKA, M REIFSNYDER, PC BRIDGETT, MM LEITER, EH AF SERREZE, DV PROCHAZKA, M REIFSNYDER, PC BRIDGETT, MM LEITER, EH TI USE OF RECOMBINANT CONGENIC AND CONGENIC STRAINS OF NOD MICE TO IDENTIFY A NEW INSULIN-DEPENDENT DIABETES RESISTANCE GENE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID GLUTAMIC-ACID DECARBOXYLASE; LT MICE; NONOBESE; MOUSE; ACTIVATION; MELLITUS; LOCUS; IDDM; HLA AB Insulin-dependent diabetes mellitus (IDDM) in NOD/Lt mice represents a complex polygenic disease. NOR/Lt is a recombinant congenic strain (RCS) in which limited regions of the NOD/Lt genome have been replaced by genome from the C57BL/KsJ strain. NOR mice are insulitis resistant and diabetes free despite genetic identity with NOD at numerous chromosomal regions containing previously described insulin-dependent diabetes (Idd) genes, including the strongly diabetogenic H2(g7) major histocompatibility complex (MHC) haplotype. The present study revealed BKs-derived genome on segments of chromosomes (Chr) 1, 2, 4, 5, 7, 11, 12, and 18, approximating 11.6% of the total NOR genome analyzed. (NOD x NOR)F-2 segregation analysis was employed to identify chromosomal regions in NOR containing Idd resistance alleles. IDDM developed in 33% (10/30) of F-1 females, and 29.3% (36/123) of F-2 females aged to 1 yr. A previously unrecognized diabetes resistance locus (designated Idd13(r) strongly protective in homozygous state was identified on NOR Chr 2 in linkage with the Il1 alpha structural gene. The existence of this locus was confirmed by construction of a NOD stock congenic for NOR-derived markers on Chr 2. Our analysis shows the utility of RCS and congenic stocks for the identification and isolation of non-MHC genes with strong antidiabetogenic functions. C1 JACKSON LAB,BAR HARBOR,ME 04609. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. FU NIDDK NIH HHS [DK-27722, DK-36175, DK-46266] NR 27 TC 121 Z9 122 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1553 EP 1558 DI 10.1084/jem.180.4.1553 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300040 PM 7931087 ER PT J AU MUELLER, DL CHEN, ZM SCHWARTZ, RH GORMAN, DM KENNEDY, MK AF MUELLER, DL CHEN, ZM SCHWARTZ, RH GORMAN, DM KENNEDY, MK TI SUBSET OF CD4+ T-CELL CLONES EXPRESSING IL-3 RECEPTOR ALPHA-CHAINS USES IL-3 AS A COFACTOR IN AUTOCRINE GROWTH SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; B-CELL; MONOCLONAL-ANTIBODY; GAMMA-CHAIN; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; MACROPHAGE ACTIVATION; LYMPHOKINE PRODUCTION; FUNCTIONAL COMPONENT; INTERLEUKIN-3 IL-3 AB In this paper we demonstrate that IL-3 can act as a cofactor for the growth of some CD4(+) T cells. This lymphokine synergized with IL-4 to induce both a unique set of protein tyrosine phosphorylations and the vigorous proliferation of the keyhole limpet hemocyanin-specific and I-A(b)-restricted CD4(+) Th0 cell clone, E6. In addition, neutralizing anti-IL-3 Abs specifically inhibited the growth of E6 T cells to Ag or anti-CD3 mAb stimulation. Finally, this T cell clone was shown to express both the IL-3R alpha-chain and an IL-3R beta-chain (AlC2A). An examination of other CD4(+) T cell clones determined that one Th1 clone (A.E7), two Th0 clones (16B.2 and L9A.1), and one Th2 clone (D10.G4.1) were not influenced by the addition of rIL-3. However, proliferation of the Th2 clones CDC25 and CDC35 to CD3-stimulation was significantly enhanced by IL-3. The sensitivity of these latter two clones to IL-3 was also found to be associated with expression of IL-3R alpha-chains. Because E6 T cells are highly dependent on IL-4 for autocrine growth similar to Th2 cells, these results suggest that IL-3 may synergize with IL-4 to enhance the proliferation of a subset of IL-4-dependent CD4(+) T cells, and the study indicates that IL-3R alpha-chain expression may be a specific marker of this CD4(+) T cell subset. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. RP MUELLER, DL (reprint author), UNIV MINNESOTA,SCH MED,DEPT MED,RHEUMATOL SECT,BOX 108 UMHC,MINNEAPOLIS,MN 55455, USA. OI Mueller, Daniel/0000-0003-1621-0419 FU NIAID NIH HHS [5 R29 AI 31669-03, 1 P01 AI 35296-01] NR 69 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1994 VL 153 IS 7 BP 3014 EP 3027 PG 14 WC Immunology SC Immunology GA PG896 UT WOS:A1994PG89600016 PM 7522247 ER PT J AU ROSENTHAL, GI GERMOLEC, DR BLAZKA, ME CORSINI, E SIMEONOVA, P POLLOCK, P KONG, LY KWON, J LUSTER, MI AF ROSENTHAL, GI GERMOLEC, DR BLAZKA, ME CORSINI, E SIMEONOVA, P POLLOCK, P KONG, LY KWON, J LUSTER, MI TI ASBESTOS STIMULATES IL-8 PRODUCTION FROM HUMAN LUNG EPITHELIAL-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NEUTROPHIL CHEMOTACTIC FACTOR; BRONCHOALVEOLAR LAVAGE; ALVEOLAR MACROPHAGES; PULMONARY FIBROSIS; MESSENGER-RNA; FACTOR-ALPHA; EXPRESSION; RELEASE; INTERLEUKIN-8 AB Studies have indicated that soluble products, including chemotactic factors, released by activated lung macrophages and fibroblasts are critical mediators in the pathogenesis of asbestos-induced pulmonary fibrosis. We provide evidence that mediators produced by lung epithelial cells in response to asbestos may also contribute to lung disease. In the present study, the carcinogenic and fibrogenic fibers, chrysotile and crocidolite asbestos, were shown to directly stimulate the human pulmonary type-II epithelial cell line, A549, and to a lesser degree primary human bronchial epithelial cells, to elicit the chemotactic cytokine IL-8 in the absence of endogenous stimuli such as IL-1 and TNF. That the membrane signaling events responsible for asbestos-induced IL-8 production are distinct from those responsible for IL-8 induction by cytokines was confirmed by using membrane-stabilizing agents and protein synthesis inhibitors. Stimulation was not observed with nonfibrogenic fibers, wollastonite and titanium dioxide, and was the direct result of asbestos-induced initiation of transcription. Asbestos failed to stimulate the release of TNF, IL-1 beta, or monocyte chemoattractant protein-1 in A549 or primary bronchial epithelial cells, indicating that cytokine secretion by asbestos is highly selective. However, a slight release of IL-1 a, probably preformed, was released in human bronchial epithelial cells. These data suggest that epithelial cells may, in addition to macrophages and fibroblasts, be an important effector cell in the immunopathogenesis of asbestos-associated diseases and in particular, in the neutrophilic infiltration that is commonly observed after asbestos exposure. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. UNIV MILAN,INST PHARMACOL SCI,MILAN,ITALY. UNIV STRATHCLYDE,DEPT IMMUNOL,GLASGOW G1 1XW,LANARK,SCOTLAND. RI Corsini, Emanuela/B-5602-2011 NR 37 TC 79 Z9 81 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 OCT 1 PY 1994 VL 153 IS 7 BP 3237 EP 3244 PG 8 WC Immunology SC Immunology GA PG896 UT WOS:A1994PG89600039 PM 8089496 ER PT J AU SPARANO, JA FISHER, RI WEISS, GR MARGOLIN, K ARONSON, FR HAWKINS, MJ ATKINS, MB DUTCHER, JP GAYNOR, ER BOLDT, DH DOROSHOW, JH ERNEST, ML SZNOL, M MIER, JW AF SPARANO, JA FISHER, RI WEISS, GR MARGOLIN, K ARONSON, FR HAWKINS, MJ ATKINS, MB DUTCHER, JP GAYNOR, ER BOLDT, DH DOROSHOW, JH ERNEST, ML SZNOL, M MIER, JW TI PHASE-II TRIALS OF HIGH-DOSE INTERLEUKIN-2 AND LYMPHOKINE-ACTIVATED KILLER-CELLS IN ADVANCED BREAST-CARCINOMA AND CARCINOMA OF THE LUNG, OVARY, AND PANCREAS AND OTHER TUMORS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN-2; LAK CELLS; ADVANCED CARCINOMA; BREAST CARCINOMA; PHASE II TRIAL ID NECROSIS-FACTOR-ALPHA; NON-HODGKINS-LYMPHOMA; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; ADOPTIVE IMMUNOTHERAPY; CONTINUOUS-INFUSION; THERAPY; COMBINATION; HEAD; NECK AB Treatment with interleukin-2 (IL-2) used alone or in combination with lymphokine-activated killer (LAK) cells is known to be an active therapy for patients with advanced renal cell carcinoma and melanoma. To further explore the activity of IL-2/LAK cell therapy in patients with advanced cancer of various primary sites, the Extramural IL-2/LAK Working Group (ILWG) initiated two phase II trials of high-dose IL-2/LAK therapy: one in patients with advanced breast carcinoma, and one in patients with advanced cancer arising in other sites. Patients with advanced renal cell carcinoma, melanoma, colorectal carcinoma, and lymphoma (Hodgkin's and B-cell non-Hodgkin's) were not eligible for the latter trial, but were treated on other ILWG trials that have been reported previously. Sixty-nine patients received high-dose IL-2 (600,000 IU/kg administered by a 15-min intravenous infusion every 8 h) on days 1-5 and days 11-15. Leukapheresis was performed for collection and ex vivo expansion of LAK cells on days 7-10, and the LAK cells were reinfused on days 11, 12, and 14. The studies were designed to determine whether treatment with IL-2/LAK resulted in at least a 40% response rate, a level of activity that was believed to be sufficient to justify the toxicity and cost of IL-2/LAK therapy. An adequate number of patients with carcinoma of the breast (N = 12), pancreas (N = 8), ovary (N = 7), and lung (non-small cell; N = 6) were accrued to assess response; most of these patients had prior chemotherapy that had failed. In addition, 32 patients with a variety of other tumor types were accrued, but accrual was not adequate to assess response in other primary tumor sites. One patient with adenocarcinoma of the breast had a partial response of 17 weeks' duration. Two patients had minor tumor regression (adenocarcinoma of the lung and spindle cell sarcoma of the lung). We conclude that high-dose IL-2/LAK is not likely to be associated with a response rate exceeding 40% for patients with carcinomas arising in the breast, pancreas, ovary, and lung (non-small cell). C1 LOYOLA UNIV,MED CTR,MAYWOOD,IL. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. CITY HOPE NATL MED CTR,DUARTE,CA. UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA. RP SPARANO, JA (reprint author), ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,CTR CANC,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [N01-CM73704, N01-CM73702, N01-CM73703] NR 53 TC 21 Z9 21 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1994 VL 16 IS 3 BP 216 EP 223 DI 10.1097/00002371-199410000-00006 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PM631 UT WOS:A1994PM63100006 PM 7834121 ER PT J AU COHEN, R JAFFE, ES STETLERSTEVENSON, MA SAUSVILLE, EA DENIGRIS, EC WOODWORTH, T FOSS, FM AF COHEN, R JAFFE, ES STETLERSTEVENSON, MA SAUSVILLE, EA DENIGRIS, EC WOODWORTH, T FOSS, FM TI BILATERAL ADRENAL HEMORRHAGE AND ADRENAL INSUFFICIENCY IN A PATIENT WITH LYMPHOMATOUS ADRENAL INFILTRATION FOLLOWING ADMINISTRATION OF A FUSION TOXIN (DAB(486)INTERLEUKIN-2) SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE DAB(486)INTERLEUKIN-2; FUSION TOXIN THERAPY ID T-CELL LYMPHOMA; PHASE-I TRIAL; INTERLEUKIN-2 RECEPTOR; PROTEIN; EXPRESSION; MALIGNANCIES; DAB486IL-2 AB DAB(486)IL-2 is a novel fusion toxin in which the ADP-ribosyltransferase and membrane-translocating domains of diphtheria toxin have been combined with the interleukin-2 (IL-2) gene, creating a recombinant protein capable of selectively intoxicating cells bearing the high-affinity IL-2 receptor. Clinical activity has been documented in Hodgkin disease and the non-Hodgkin lymphomas; toxicities have been minimal and include mild hepatic transaminitis, proteinurea, and hypersensitivity reactions. In this report, a patient with tumor-stage cutaneous T-cell lymphoma developed clinical adrenal failure with bilateral adrenal hemorrhage and necrosis 7 weeks after completing a 5-day course of treatment with DAB(486)IL-2. The relationship of fusion toxin therapy to the development of this unusual toxicity is discussed. C1 USN,NCI,MED ONCOL BRANCH,BETHESDA,MD. BETHESDA NAVAL HOSP,DEPT PATHOL,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD. NCI,PATHOL LAB,BETHESDA,MD. NCI,BIOL CHEM LAB,BETHESDA,MD. SERAGEN INC,HOPKINTON,MA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1994 VL 16 IS 3 BP 229 EP 233 DI 10.1097/00002371-199410000-00008 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PM631 UT WOS:A1994PM63100008 PM 7834123 ER PT J AU GIORGI, JV HO, HN HIRJI, K CHOU, CC HULTIN, LE OROURKE, S PARK, L MARGOLICK, JB FERBAS, J PHAIR, JP SAAH, AJ ARMENIAN, H FARZADEGAN, H GRAHAM, N MCARTHUR, J PALENICEK, J MUNOZ, A HOOVER, D GALAI, N JACOBSON, LP PIANTADOSI, S SU, S BAUER, K CHMIEL, JS COHEN, B VARIAKOJIS, D WESCH, J WOLINSKY, SM DETELS, R VISSCHER, BR CHEN, I DUDLEY, J FAHEY, JL MARTINEZMAZA, O NISHANIAN, P TAYLOR, J ZACK, J RINALDO, CR BECKER, JT GUPTA, P HO, M KINGSLEY, L SCHRAGER, L KASLOW, RA VANRADEN, MJ SEMINARA, D AF GIORGI, JV HO, HN HIRJI, K CHOU, CC HULTIN, LE OROURKE, S PARK, L MARGOLICK, JB FERBAS, J PHAIR, JP SAAH, AJ ARMENIAN, H FARZADEGAN, H GRAHAM, N MCARTHUR, J PALENICEK, J MUNOZ, A HOOVER, D GALAI, N JACOBSON, LP PIANTADOSI, S SU, S BAUER, K CHMIEL, JS COHEN, B VARIAKOJIS, D WESCH, J WOLINSKY, SM DETELS, R VISSCHER, BR CHEN, I DUDLEY, J FAHEY, JL MARTINEZMAZA, O NISHANIAN, P TAYLOR, J ZACK, J RINALDO, CR BECKER, JT GUPTA, P HO, M KINGSLEY, L SCHRAGER, L KASLOW, RA VANRADEN, MJ SEMINARA, D TI CD8+ LYMPHOCYTE-ACTIVATION AT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SEROCONVERSION - DEVELOPMENT OF HLA-DR+ CD38- CD8+ CELLS IS ASSOCIATED WITH SUBSEQUENT STABLE CD4+ CELL LEVELS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MULTICENTER AIDS COHORT; IMMUNE-DEFICIENCY-SYNDROME; T-CELLS; HIV-INFECTION; PROGNOSTIC VALUE; HOMOSEXUAL MEN; REPLICATION; EXPRESSION; ANTIGENS; CULTURE AB Subsets of activated CD8(+) lymphocytes defined by membrane expression of the activation antigens HLA-DR and CD38 were counted by three-color flow cytometry in homosexual men who subsequently became seropositive for human immunodeficiency virus type 1 (HIV). Profound CD8(+) cell activation was seen in all subjects at seroconversion and 6 and 12 months later. The HLA-DR(+) CD38(+) CD8(+) cell population, which has potent direct HIV cytotoxic T cell activity, was markedly elevated at seroconversion in all subjects. In some men, these levels remained elevated throughout the first year of infection. During the next 5 years, these men had stable CD4(+) cell levels, whereas the others did not. Long-term survivors (seropositive for 9 years, > 800 CD4(+) cells/mm(3)) also had elevated levels of this subset, despite few other activated CD8(+) cells. Thus, selective elevation of HLA-DR(+) CD38(-) CD8(+) cells was a marker of subsequent stable HIV disease. C1 UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,DEPT BIOMATH,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90024. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. UNIV PITTSBURGH,SCH PUBL HLTH,PITTSBURGH,PA 15260. NORTHWESTERN UNIV,SCH MED,CTR COMPREHENS AIDS,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,HOWARD BROWN MEM CLIN,CHICAGO,IL 60611. NIH,BETHESDA,MD 20892. RI Wolinsky, Steven/B-2893-2012 FU NIAID NIH HHS [AI-32883, AI-35040, AI-28697] NR 29 TC 160 Z9 160 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 OCT PY 1994 VL 170 IS 4 BP 775 EP 781 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PJ694 UT WOS:A1994PJ69400004 PM 7930717 ER PT J AU GRAHAM, BS GORSE, GJ SCHWARTZ, DH KEEFER, MC MCELRATH, MJ MATTHEWS, TJ WRIGHT, PF BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L BOLOGNESI, DP STABLEIN, DM ESTERLITZ, JR HU, SL SMITH, GE AF GRAHAM, BS GORSE, GJ SCHWARTZ, DH KEEFER, MC MCELRATH, MJ MATTHEWS, TJ WRIGHT, PF BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L BOLOGNESI, DP STABLEIN, DM ESTERLITZ, JR HU, SL SMITH, GE TI DETERMINANTS OF ANTIBODY-RESPONSE AFTER RECOMBINANT GP160 BOOSTING IN VACCINIA-NAIVE VOLUNTEERS PRIMED WITH GP160-RECOMBINANT VACCINIA VIRUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ENVELOPE GLYCOPROTEIN; IMMUNODEFICIENCY; IMMUNOGENICITY; VACCINATION; LYMPHOCYTES; ADULTS; SAFETY; HUMANS AB Priming with a live recombinant vector followed by subunit boosting is a promising strategy for human immunodeficiency virus (HIV) immunization. Twenty-nine vaccinia-naive volunteers were primed with gp160-recombinant vaccinia virus (HIVAC-1e) and boosted with recombinant (r) gp160 to define factors associated with the magnitude and specificity of antibody response after booster immunization. A longer interval between inoculation and boost, two inoculations of HIVAC-1e with lesion formation occurring after the first, and Western blot-detectable antibody to gp160 after inoculation were significantly associated with higher neutralizing antibody titers and fusion-inhibiting activity after boosting. HIVAC-1e-primed vaccinees were more likely to have antibody to V3- and CD4-binding regions of gp120 and less likely to have antibody to constant regions 2 and 3 than vaccinees immunized with rgp160 alone. Priming volunteers with HIVAC-1e was a key determinant of the epitope specificity and magnitude of functional antibody responses induced by rgp160 boosting. C1 DUKE UNIV,MED CTR,DURHAM,NC. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63103. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. MICROGENESYS INC,MERIDEN,CT. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD. RP GRAHAM, BS (reprint author), VANDERBILT UNIV,SCH MED,DEPT MED,DIV INFECT DIS,A-3310 MCN,NASHVILLE,TN 37232, USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NIAID NIH HHS [AI-05061, AI-05062, AI-82500] NR 13 TC 43 Z9 44 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1994 VL 170 IS 4 BP 782 EP 786 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PJ694 UT WOS:A1994PJ69400005 PM 7930718 ER PT J AU ROILIDES, E HOLMES, A BLAKE, C VENZON, D PIZZO, PA WALSH, TJ AF ROILIDES, E HOLMES, A BLAKE, C VENZON, D PIZZO, PA WALSH, TJ TI ANTIFUNGAL ACTIVITY OF ELUTRIATED HUMAN MONOCYTES AGAINST ASPERGILLUS-FUMIGATUS HYPHAE - ENHANCEMENT BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERFERON-GAMMA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FUNGICIDAL ACTIVITY; POLYMORPHONUCLEAR LEUKOCYTES; RECOMBINANT; INVITRO; ACTIVATION; MECHANISM; DAMAGE; REQUIREMENTS; NEUTROPHILS; AUGMENTS AB Human monocytes are important effector cells in host defenses against Asgergillus hyphae, and as elutriated monocytes (EHM) they may be transfused in large quantities to leukopenic patients with invasive aspergillosis. The antifungal activity of EHM against Aspergillus hyphae was compared with that of polymorphonuclear leukocytes (PMNL). The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on superoxide anion (O-2(-)) release and on hyphal damage caused by EHM against unopsonized A. fumigatus hyphae was investigated. EHM had antihyphal activity comparable to that of PMNL. GM-CSF significantly augmented O-2(-) release by EHM in response to PMA. Also, both GM-CSF and IFN-gamma significantly enhanced the antifungal activity of EHM compared with untreated controls. Thus, EHM have demonstrable antifungal activity against Aspergillus hyphae that may be increased by GM-CSF and IFN-gamma, suggesting their potential therapeutic role in immune reconstitution of effector cells. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 23 TC 106 Z9 109 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 OCT PY 1994 VL 170 IS 4 BP 894 EP 899 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PJ694 UT WOS:A1994PJ69400022 PM 7930733 ER PT J AU WILLIAMS, ME MONTENEGRO, S DOMINGUES, AL WYNN, TA TEIXEIRA, K MAHANTY, S COUTINHO, A SHER, A AF WILLIAMS, ME MONTENEGRO, S DOMINGUES, AL WYNN, TA TEIXEIRA, K MAHANTY, S COUTINHO, A SHER, A TI LEUKOCYTES OF PATIENTS WITH SCHISTOSOMA-MANSONI RESPOND WITH A TH2 PATTERN OF CYTOKINE PRODUCTION TO MITOGEN OR EGG ANTIGENS BUT WITH A TH0 PATTERN TO WORM ANTIGENS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GRANULOMA-FORMATION; PROTECTIVE IMMUNITY; HELMINTH INFECTION; INTERFERON-GAMMA; PARASITE ANTIGEN; DOWN-REGULATION; IFN-GAMMA; IL-4; INDUCTION; ANTIBODIES AB Cytokine responses of peripheral blood mononuclear cells from humans infected with Schistosoma mansoni were assessed. By ELISA and ELISPOT, persons with acute and hepatosplenic infections produced higher levels of interleukin (IL)-4 and IL-5 and higher frequencies of IL-4-producing cells in response to mitogen than did uninfected persons. In contrast, mitogen-induced production of the Th1 cytokine interferon-gamma (IFN-gamma) did not differ from that of uninfected controls. Upon stimulation with egg antigens, many patients responded with elevated IL-4 mRNA levels but displayed no appreciable increases in Th1 (i.e., IFN-gamma and IL-2) cytokine transcripts. Nevertheless, in cells stimulated with adult worm antigen, a more mixed Th0-type response was observed with production of both Th1 and Th2 cytokines. These results support previous findings in laboratory mice that schistosome infection results in increased production of Th2 cytokines. Unlike mice, infected humans do not display a generalized down-modulation in Th1 responses but instead show a selective deficiency in IFN-gamma and usually IL-2 responses to egg antigens. C1 NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,CLIN PARASITOL SECT,BETHESDA,MD 20892. CTR PESQUISAS AGGEU MAGALHAES,RECIFE,PE,BRAZIL. RI Wynn, Thomas/C-2797-2011; OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 26 TC 70 Z9 70 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 OCT PY 1994 VL 170 IS 4 BP 946 EP 954 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PJ694 UT WOS:A1994PJ69400030 PM 7930740 ER PT J AU STEEL, C LUJANTRANGAY, A GONZALEZPERALTA, C ZEAFLORES, G NUTMAN, TB AF STEEL, C LUJANTRANGAY, A GONZALEZPERALTA, C ZEAFLORES, G NUTMAN, TB TI TRANSIENT CHANGES IN CYTOKINE PROFILES FOLLOWING IVERMECTIN TREATMENT OF ONCHOCERCIASIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL CLONES; MEDIATED IMMUNE-RESPONSES; VOLVULUS INFECTION; PARASITE ANTIGEN; INTERFERON-GAMMA; IL-10; MANSONI; HUMANS; DIETHYLCARBAMAZINE; HYPERSENSITIVITY AB Cytokine production by peripheral blood mononuclear cells after antigen or mitogen stimulation was assessed before and after semiannual ivermectin treatment of 27 patients with onchocerciasis. Before treatment, Onchocerca volvulus antigen (OvA) elicited interleukin (IL)-5 production but inhibited production of IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha. Six months after the first dose of ivermectin, there were increases in the IL-2, IL-4, IL-5, and interferon-gamma responses to mitogen and in the GM-CSF and IL-10 responses to OvA. By 24 months (after four ivermectin doses), OvA-induced GM-CSF production and mitogen-induced IL-2 and IL-10 production remained elevated above pretreatment levels, whereas that of other cytokines returned to or below pretreatment levels. These transient changes in cytokine response profiles of patients with onchocerciasis following ivermectin treatment likely reflect changes in antigen load. C1 MINIST PUBL HLTH,SNEM,GUATEMALA CITY,GUATEMALA. RP STEEL, C (reprint author), NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 41 TC 18 Z9 18 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 OCT PY 1994 VL 170 IS 4 BP 962 EP 970 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PJ694 UT WOS:A1994PJ69400032 PM 7930742 ER PT J AU MCINTOSH, K PITT, J BRAMBILLA, D CARROLL, S DIAZ, C HANDELSMAN, E MOYE, J RICH, K AF MCINTOSH, K PITT, J BRAMBILLA, D CARROLL, S DIAZ, C HANDELSMAN, E MOYE, J RICH, K TI BLOOD CULTURE IN THE FIRST 6 MONTHS OF LIFE FOR THE DIAGNOSIS OF VERTICALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID POLYMERASE CHAIN-REACTION; HIV-INFECTION; CHILDREN; INFANTS; ANTIGEN; TRANSMISSION; MOTHERS; WOMEN AB Serial blood cultures over the first 6 months of life in 310 infants with vertical exposure to human immunodeficiency virus (HIV) in the Women and Infants Transmission Study were analyzed to determine their value for early diagnosis of HIV infection. Cultures were done at 0-7 days and 1, 2, 4, and 6 months of age: 55 infants were infected. Blood culture sensitivity in infected children was 24% (7/29) during the first week of life and 85%, 91%, 82%, and 88%, respectively, at 1, 2, 4, and 6 months. The sensitivity, specificity, and positive and negative predictive values of a single culture between 1 and 6 months of age were, respectively, 86.9%, 99.6%, 97.9%, and 97.5%. Two negative cultures between 1 and 6 months of age defined an uninfected infant with a specificity of 99.2%-100.0%. Blood culture done between 1 and 6 months of age in children of HIV-positive mothers is a sensitive and specific test for HIV infection, with high positive and negative predictive values. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PEDIAT,DIV INFECT DIS,NEW YORK,NY. SUNY HLTH SCI CTR,BROOKLYN,NY. NIAID,DIV AIDS,VACCINE TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD 20892. NICHHD,ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. UNIV PUERTO RICO,DEPT PEDIAT,SAN JUAN,PR 00936. UNIV ILLINOIS,DEPT PEDIAT,CHICAGO,IL. RP MCINTOSH, K (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,DIV INFECT DIS,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [AI-85005, AI-82506, AI-82507] NR 16 TC 95 Z9 95 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1994 VL 170 IS 4 BP 996 EP 1000 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PJ694 UT WOS:A1994PJ69400037 PM 7930747 ER PT J AU NURDEN, P BIHOUR, C COMBRIE, R GRALNICK, H NURDEN, AT AF NURDEN, P BIHOUR, C COMBRIE, R GRALNICK, H NURDEN, AT TI GLYCOPROTEIN IA-IIA (VLA-2) AND GLYCOPROTEIN IB-IX COMPLEXES ARE PROCESSED INDEPENDENTLY DURING THROMBIN-INDUCED PLATELET ACTIVATION SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID ACTIN-BINDING PROTEIN; VONWILLEBRAND-FACTOR-BINDING; MEMBRANE SKELETON; MONOCLONAL-ANTIBODIES; ADHESIVE PROTEINS; IIIA COMPLEX; COLLAGEN; SURFACE; IDENTIFICATION; REDISTRIBUTION AB We have previously shown that when human platelets are stimulated by thrombin, glycoprotein Ib-IX (GP Ib-IX) complexes are cleared to the surface-connected canalicular system (Blood 1990;76:1503). The question arose as to whether GP Ia-IIa complexes (VLA-2), another adhesion receptor thought to be linked to the membrane cytoskeleton, behaved similarly. Monoclonal antibodies to GP Ia-IIa were used in either (1) immunofluorescence procedures and flow cytometry or (2) immunogold staining and electron microscopy. In flow cytometry, VLA-2 was shown to have a low but variable expression in the platelets of different donors. Immunogold staining showed that the complexes were regularly distributed over the platelet surface. This was best seen after staining of paraformaldehyde-fixed whole mounts, where bound antibodies were often visualized in small clusters. The surface expression of VLA-2 receptors increased somewhat after thrombin stimulation, the receptors coming from a small intracellular pool revealed by flow cytometric analysis of Triton X-100-permeabilized cells. Immunogold staining showed that after activation the receptors were equally as present on pseudopods as on the peripheral zone of the platelet. Down-regulation, as seen with GP Ib-IX complexes, was not observed. Our results therefore show that two-way trafficking of adhesion receptors can occur during platelet activation. This would imply that GP Ib-IX and VLA-2 are attached to different elements within the membrane cytoskeleton. C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP NURDEN, P (reprint author), HOP CARDIOL,HEMOBIOL LAB,CNRS,URA 1464,F-33604 PESSAC,FRANCE. NR 43 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD OCT PY 1994 VL 124 IS 4 BP 579 EP 588 PG 10 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA PM244 UT WOS:A1994PM24400018 PM 7930882 ER PT J AU ROSENBERG, HF TIFFANY, HL AF ROSENBERG, HF TIFFANY, HL TI CHARACTERIZATION OF THE EOSINOPHIL GRANULE PROTEINS RECOGNIZED BY THE ACTIVATION-SPECIFIC ANTIBODY EG2 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE GRANULOCYTES; RIBONUCLEASES; TOXINS; MONOCLONAL ANTIBODIES; GLYCOSYLATION ID MESSENGER-RNA EXPRESSION; MAJOR BASIC-PROTEIN; AMINO-ACID-SEQUENCE; CATIONIC PROTEIN; MOLECULAR-CLONING; MONOCLONAL-ANTIBODIES; NEUROTOXIN; RIBONUCLEASE; CDNA AB Monoclonal antibodies EG1. and EG2 have the unique ability to distinguish the storage from the secreted forms of the eosinophil cationic protein (ECP). EG2 has been used extensively as a marker for activated, secreting eosinophils, despite the fact that no biochemical differences between the storage and secreted forms of ECP have been identified. We have determined that the activation-specific EG2 detects only one of three distinct glycosylated forms of ECP (18 kDa); in contrast, both EG1 and polyclonal anti-ECP antiserum can detect three glycosylated forms of this protein (18, 20, and 22 kDa). We have also determined that EG2 detects fully deglycosylated ECP as well as fully deglycosylated eosinophil-derived neurotoxin. Our results indicate that activation-specific EG2 recognizes a polypeptide epitope that is masked in the higher-molecular-weight, more heavily glycosylated forms of ECP. These findings suggest that deglycosylation may occur in conjunction with activation and secretion; alternatively, the 18-kDa form of ECP may be present in the storage granule of resting eosinophils but may remain undetected in an inaccessible location or conformation. C1 GEORGE WASHINGTON UNIV,GRAD PROGRAM GENET,WASHINGTON,DC. RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N104,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 30 Z9 30 U1 0 U2 1 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 OCT PY 1994 VL 56 IS 4 BP 502 EP 506 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA PK360 UT WOS:A1994PK36000012 PM 7930947 ER PT J AU KRAEMER, FB SATHER, SA PARK, B SZTALRYD, C NATU, V MAY, K NISHIMURA, H SIMPSON, I COOPER, AD CUSHMAN, SW AF KRAEMER, FB SATHER, SA PARK, B SZTALRYD, C NATU, V MAY, K NISHIMURA, H SIMPSON, I COOPER, AD CUSHMAN, SW TI LOW-DENSITY-LIPOPROTEIN RECEPTORS IN RAT ADIPOSE-CELLS - SUBCELLULAR-LOCALIZATION AND REGULATION BY INSULIN SO JOURNAL OF LIPID RESEARCH LA English DT Article DE SUBFRACTIONS; SYNTHESIS; HALF-LIFE; RAT ID HEP G2 CELLS; PLASMA-MEMBRANE; LDL-RECEPTOR; GLUCOSE-TRANSPORT; ALPHA-2-MACROGLOBULIN RECEPTOR; STIMULATED TRANSLOCATION; INTRACELLULAR-TRANSPORT; TRANSFERRIN RECEPTORS; CHOLESTEROL-SYNTHESIS; POTENTIAL MECHANISM AB The distribution of LDL receptors within subcellular compartments of isolated rat adipose cells and the effects of insulin on their expression have been assessed. By immunoblotting with specific anti-rat LDL receptor antibodies, LDL receptors were 2.3- and 4.5-fold enriched in endoplasmic reticulum-rich high-density microsomes (HDM) and Golgi complex-rich low-density microsomes (LDM), respectively, compared to plasma membranes (PM). This distribution was similar in cultured cells in which total receptors were increased 2.5-fold compared to freshly isolated cells. After correction for enzyme recoveries, LDL receptors were distributed similar to 4% in HDM, similar to 73% in LDM, and similar to 23% in PM. Insulin decreased total LDL receptors in adipose cells similar to 44%, with a 48% and 49% decrease in HDM and LDM, respectively, without any changes in PM. In contrast, insulin caused an increase of glucose transporters in PM while also decreasing glucose transporters in LDM. When adipose cells were depleted of potassium to inhibit receptor-mediated endocytosis, insulin again caused a decrease of LDL receptors in LDM but now increased LDL receptors in PM. Insulin increased the rate of LDL receptor synthesis similar to 24%, but decreased their half life similar to 40%. Thus, in isolated adipose cells the majority of LDL receptors appear to be located in an intracellular compartment that co-sediments with the Golgi complex rather than located in the PM. The LDL receptors localized in intracellular compartments seem to be functionally regulated as insulin acutely diminishes the number of receptors by apparently accelerating their rate of degradation through, as yet, incompletely determined mechanisms. C1 STANFORD UNIV,SCH MED,DEPT MED,STANFORD,CA 94305. PALO ALTO MED FDN,RES INST,PALO ALTO,CA 94301. NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. RP KRAEMER, FB (reprint author), VET ADM MED CTR,PALO ALTO,CA 94304, USA. FU NHLBI NIH HHS [HL 42865]; NIDDK NIH HHS [DK 38318, DK 36659] NR 58 TC 15 Z9 15 U1 0 U2 1 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 OCT PY 1994 VL 35 IS 10 BP 1760 EP 1772 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PM253 UT WOS:A1994PM25300004 PM 7852853 ER PT J AU IKEWAKI, K RADER, DJ ZECH, LA BREWER, HB AF IKEWAKI, K RADER, DJ ZECH, LA BREWER, HB TI IN-VIVO METABOLISM OF APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-E IN PATIENTS WITH ABETALIPOPROTEINEMIA - IMPLICATIONS FOR THE ROLES OF APOLIPOPROTEIN-B AND APOLIPOPROTEIN-E IN HDL METABOLISM SO JOURNAL OF LIPID RESEARCH LA English DT Article DE APOA-I; APOE; KINETICS; RADIOTRACER; HIGH DENSITY LIPOPROTEINS ID HIGH-DENSITY-LIPOPROTEIN; HUMAN-PLASMA LIPOPROTEINS; ESTER TRANSFER PROTEIN; RECEPTOR-BINDING ACTIVITY; CHOLESTERYL ESTER; APOPROTEIN-E; APOA-I; INVIVO METABOLISM; PARTICLES; SUBPOPULATIONS AB The metabolism of high density lipoproteins (HDL) is tightly linked to the metabolism of apoB-containing lipoproteins through the exchange and transfer of lipids and apolipoproteins within the plasma compartment. Abetalipoproteinemia (ABL), a genetic disease in which apoB is absent from the plasma and HDL are the sole plasma lipoproteins, is a model for the investigation of HDL metabolism without modification by apoB-containing lipoproteins. Apolipoproteins A-I and E are two of the major apolipoproteins in HDL. Plasma apoA-I levels, but not apoE levels, have been reported to be decreased in patients with ABL. Furthermore, HDL from ABL patients is enriched in apoE compared with normal subjects. The purpose of the present study was: 1) to elucidate the metabolic basis of the low apoA-I levels in ABL; 2) to determine whether in vivo apoE production rates are normal in the absence of apoB-lipoprotein secretion; and 3) to test the hypothesis that apoE influences apoA-I and HDL catabolism in ABL. I-131-labeled apoA-I and I-125-labeled apoE were reassociated with autologous lipoproteins and injected into two unrelated ABL patients and control subjects. The mean residence time of apoA-I in ABL (2.4 days) was significantly decreased by nearly 50% compared with control subjects (4.7 +/- 0.6 days). ApoA-I production rates were also significantly decreased by 40% in ABL (7.1 mg/kg-d) compared with control subjects (11.8 +/- 1.7 mg/kg-d). The mean residence lime of apoE in ABL (0.50 days) was somewhat shorter than that of control subjects (0.66 +/- 0.15 days), whereas the mean apoE production rate in ABL (2.14 mg/kg-d) was not substantially different from that of control subjects(1.55 +/- 0.62 mg/kg-d). HDL subfractions LpA-I and LpA-I:A-II were isolated using immunoaffinity chromatography. In contrast to the normal metabolism apoA-I in LpA-I:A-II particles was catabolized at a faster rate than apoA-I in LpA-I, accounting for the greater decrease of plasma LpA-I:A-II relative to LpA-I in the ABL patients. HDL subfractions with and without apoE were also isolated using anti-apoE immunoaffinity chromatography. Labeled apoA-I in apoE-containing HDL was catabolized faster than that in HDL without apoE. Among the three different forms of apoE, the apoE monomer was catabolized at the fastest rate, the apoE homodimer at an intermediate rate, and the apoE-A-II heterodimer had the slowest rate of catabolism. In conclusion, decreased apoA-I levels in ABL are due to both a decreased rate of apoA-I production as well as an increased rate of apoA-I catabolism, in particular that of apoA-I in LpA-I:A-II. Despite the lack of secretion of apoB-containing lipoproteins, apoE production is not impaired in ABL. These results provide insight into the role of apoB and apoE in HDL metabolism. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 67 TC 26 Z9 26 U1 0 U2 1 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 OCT PY 1994 VL 35 IS 10 BP 1809 EP 1819 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PM253 UT WOS:A1994PM25300009 PM 7852858 ER PT J AU ZHU, GA RENWICK, A BAX, A AF ZHU, GA RENWICK, A BAX, A TI MEASUREMENT OF 2-BOND AND 3-BOND H-1-C-13 J-COUPLINGS FROM QUANTITATIVE HETERONUCLEAR J-CORRELATION FOR MOLECULES WITH OVERLAPPING H-1 RESONANCES, USING T(1) NOISE-REDUCTION SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Note ID LONG-RANGE C-13; DETECTED MEASUREMENTS; NMR-SPECTRA; CONSTANTS; PROTEINS; INVERSE; SPECTROSCOPY; ASSIGNMENT C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. INT MED COLL,PETALING JAYA 46050,MALAYSIA. UNIV MARYLAND,DEPT ELECT ENGN,COLLEGE PK,MD 20742. NR 29 TC 36 Z9 36 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD OCT PY 1994 VL 110 IS 2 BP 257 EP 261 DI 10.1006/jmra.1994.1214 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA PL360 UT WOS:A1994PL36000018 ER PT J AU WANG, AC LODI, PJ QIN, J VUISTER, GW GRONENBORN, AM CLORE, GM AF WANG, AC LODI, PJ QIN, J VUISTER, GW GRONENBORN, AM CLORE, GM TI AN EFFICIENT TRIPLE-RESONANCE EXPERIMENT FOR PROTON-DIRECTED SEQUENTIAL BACKBONE ASSIGNMENT OF MEDIUM-SIZED PROTEINS SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID ISOTOPICALLY ENRICHED PROTEINS; NMR-SPECTRA; SPECTROSCOPY; AMIDE; PHASE C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 14 TC 39 Z9 39 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD OCT PY 1994 VL 105 IS 2 BP 196 EP 198 DI 10.1006/jmrb.1994.1123 PG 3 WC Physics, Atomic, Molecular & Chemical SC Physics GA PN454 UT WOS:A1994PN45400015 PM 7952935 ER PT J AU BOLDTHOULE, DM NIGIDA, SM RINALDO, CR EHRLICH, GD AF BOLDTHOULE, DM NIGIDA, SM RINALDO, CR EHRLICH, GD TI THE T-CELL RECEPTOR V-BETA REPERTOIRE IN NAIVE AND HUMAN IMMUNODEFICIENCY VIRUS-1 (HIV-1) INFECTED CHIMPANZEES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE CELLULAR IMMUNOLOGY; POLYMERASE CHAIN REACTION (PCR); ACQUIRED IMMUNODEFICIENCY; SYNDROME (AIDS); SUPERANTIGENS (SASS) ID POLYMERASE CHAIN-REACTION; DIFFERENTIAL EXPRESSION; SEGMENT FREQUENCIES; LYMPHOCYTES-T; GENES; AIDS; SUPERANTIGEN; USAGE; CD4+; DEPLETION AB Using a panel of human T-cell receptor (TCR) variable region beta chain (V beta) polymerase chain reaction (PCR) primers, we performed cross-sectional and longitudinal analyses of the TCR V beta repertoire in naive and HIV-1 infected chimpanzees. We demonstrate that our TCR PCR primer panel will support amplification of chimpanzee cDNA from most of the TCR V beta families. However, no differences in TCR V beta expression were found between the naive and HIV-1 infected chimpanzees, unlike the TCR V beta repertoire perturbation found in HIV-1 infected human subjects. This finding suggests that a complete TCR repertoire in HIV-1 infected chimpanzees is associated with the maintenance CD4 + T-cell numbers and lack of progression to AIDS. C1 UNIV PITTSBURGH,SCH MED,DEPT PATHOL,CORE PCR FACIL,PITTSBURGH,PA 15261. NCI,FREDERICK CTR,VIRAL DIS & IMMUN SECT,FREDERICK,MD 21701. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT INFECT DIS,PITTSBURGH,PA. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT MICROBIOL,PITTSBURGH,PA. UNIV PITTSBURGH,DEPT OTOLARYNGOL,PITTSBURGH,PA 15260. FU NIAID NIH HHS [N01-AI72632] NR 33 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 1994 VL 23 IS 8 BP 432 EP 441 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA QT478 UT WOS:A1994QT47800003 PM 7602579 ER PT J AU FULLER, RW CARDELLINA, JH CRAGG, GM BOYD, MR AF FULLER, RW CARDELLINA, JH CRAGG, GM BOYD, MR TI CUCURBITACINS - DIFFERENTIAL CYTOTOXICITY, DEREPLICATION AND FIRST ISOLATION FROM GONYSTYLUS-KEITHII SO JOURNAL OF NATURAL PRODUCTS LA English DT Note AB A characteristic pattern of differential cytotoxicity of extracts of Iberis amara seeds, predominantly toward renal tumor, brain rumor, and melanoma cell lines in the NCI human disease-oriented tumor screening panel, was traced to cucurbitacins E [1] and I [2]. This same differential cytotoxicity profile was detected in extracts of Begonia plebeja and Gonystylus keithii. Computer-assisted recognition of these profiles was followed by a rapid chemical fractionation, thus permitting the efficient dereplication of chose extracts containing cucurbitacins B [3] and D [4], respectively. This is the first report of cucurbitacins from the genus Gonystylus. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 12 TC 31 Z9 35 U1 1 U2 2 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 1994 VL 57 IS 10 BP 1442 EP 1445 DI 10.1021/np50112a015 PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA PU017 UT WOS:A1994PU01700015 PM 7807128 ER PT J AU BITLER, DA LINNOILA, M GEORGE, DT AF BITLER, DA LINNOILA, M GEORGE, DT TI PSYCHOSOCIAL AND DIAGNOSTIC CHARACTERISTICS OF INDIVIDUALS INITIATING DOMESTIC VIOLENCE SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Note C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. GEORGE MASON UNIV,COLL ARTS & SCI,OFF DEAN,FAIRFAX,VA 22030. NR 9 TC 10 Z9 11 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1994 VL 182 IS 10 BP 583 EP 585 DI 10.1097/00005053-199410000-00009 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PL029 UT WOS:A1994PL02900009 PM 7931207 ER PT J AU NEWMAN, JD AF NEWMAN, JD TI PRIMATE BEHAVIOR - INFORMATION, SOCIAL KNOWLEDGE, AND THE EVOLUTION OF CULTURE - QUIATT,D, REYNOLDS,V SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP NEWMAN, JD (reprint author), NICHHD,POOLESVILLE,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 1994 VL 182 IS 10 BP 598 EP 599 DI 10.1097/00005053-199410000-00025 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PL029 UT WOS:A1994PL02900022 ER PT J AU MOFFETT, JR ESPEY, MG SAITO, K NAMBOODIRI, MAA AF MOFFETT, JR ESPEY, MG SAITO, K NAMBOODIRI, MAA TI QUINOLINIC ACID IMMUNOREACTIVE CELLS IN THE CHOROID-PLEXUS, LEPTOMENINGES AND BRAIN VASCULATURE OF THE IMMUNE-STIMULATED GERBIL SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE IMMUNOHISTOCHEMISTRY; EXCITOTOXIN; MACROPHAGE; CEREBROSPINAL FLUID; BLOOD-BRAIN BARRIER ID KYNURENINE PATHWAY METABOLISM; METHYL-D-ASPARTATE; CEREBROSPINAL-FLUID; NEUROACTIVE KYNURENINES; L-TRYPTOPHAN; RAT; INDOLEAMINE-2,3-DIOXYGENASE; LOCALIZATION; ACTIVATION; INTERFERON AB Antibodies to quinolinic acid were utilized to study the cellular localization of this endogenous neurotoxin in the gerbil brain subsequent to systemic immune stimulation with pokeweed mitogen. Immunohistochemistry of carbodiimide fixed spleen revealed a dramatic increase in the number of quinolinic acid-positive cells in the red pulp in the immune-stimulated animals. Quinolinic acid immunoreactivity in the brain was observed in cells within the choroid plexus, vasculature and leptomeninges of the stimulated group only. No immunoreactivity was observed in brain parenchyma. These results are supportive of an immune system origin for the increases in quinolinic acid in CSF and brain during immune stimulation in a rodent model system. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RP MOFFETT, JR (reprint author), GEORGETOWN UNIV,DEPT BIOL,37TH & 0 STS NW,WASHINGTON,DC 20057, USA. FU NEI NIH HHS [EY09085]; NIDDK NIH HHS [DK37024] NR 24 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 1994 VL 54 IS 1-2 BP 69 EP 73 DI 10.1016/0165-5728(94)90232-1 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PL703 UT WOS:A1994PL70300008 PM 7929805 ER PT J AU PETRALIA, RS WANG, YX WENTHOLD, RJ AF PETRALIA, RS WANG, YX WENTHOLD, RJ TI THE NMDA RECEPTOR SUBUNITS NR2A AND NR2B SHOW HISTOLOGICAL AND ULTRASTRUCTURAL-LOCALIZATION PATTERNS SIMILAR TO THOSE OF NR1 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE EXCITATORY AMINO ACIDS; ULTRASTRUCTURE; IMMUNOCYTOCHEMISTRY; AMPA; HIPPOCAMPUS; CEREBELLUM ID D-ASPARTATE-RECEPTOR; PRESYNAPTIC GLUTAMATE-RECEPTOR; LONG-TERM POTENTIATION; CENTRAL NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; RAT-BRAIN; MOLECULAR-CLONING; IMMUNOCYTOCHEMICAL LOCALIZATION; METABOTROPIC RECEPTOR; SYNAPTIC PLASTICITY AB Neuronal plasticity associated with learning, memory and development is controlled, in part, by NMDA receptors, which are complexes consisting of the subunit NMDAR1 (NR1) and one or more NMDAR2 subunits (NR2A-NR2D). We made a polyclonal antibody to a C-terminus peptide of NR2A. In analysis of transfected cell membranes, this antibody recognizes NR2A and NR2B, and to a slight extent, NR2C and NR2D. In Western blots of rat brain, the antibody labeled a single band that comigrated with NR2A and NR2B. This antibody (NR2A/B) did not cross-react with extracts from transfected cells expressing other glutamate receptor subunits, nor did it label non-neuronal tissues. Immunostained sections of rat brain showed significant staining throughout the nervous system, including olfactory bulb, cerebral cortex, hippocampus, caudate-putamen, and many brainstem nuclei, as well as in neurons of spinal cord and sensory ganglia. This widespread distribution of staining was similar to that found with an antibody to NR1, supporting the presence of functional NR1/NR2 complexes throughout the nervous system. In the cerebellum, in contrast to staining with NR1 antibody, Purkinje cell staining with NR2A/B antibody was low, indicating that these neurons may lack functional NMDA receptors. EM examination revealed dense staining in dendrites and postsynaptic densities in cerebral cortex and hippocampus, similar to those seen with antibody to NR1. Since functional NMDA receptor complexes at synapses appear to require both NR1 and NR2 subunit proteins for full function, this study provides structural evidence for functional NR1/NR2 receptors in vivo in the nervous system. RP PETRALIA, RS (reprint author), NIDCD, NEUROCHEM LAB, BLDG 36, ROOM 5D-08, BETHESDA, MD 20892 USA. NR 72 TC 331 Z9 340 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT PY 1994 VL 14 IS 10 BP 6102 EP 6120 PG 19 WC Neurosciences SC Neurosciences & Neurology GA PL028 UT WOS:A1994PL02800031 PM 7931566 ER PT J AU HUERTA, MF CURVEY, MF KOSLOW, SH AF HUERTA, MF CURVEY, MF KOSLOW, SH TI NEUROTECHNOLOGY - EXPANDING OPPORTUNITIES FOR FUNDING AT THE NATIONAL-INSTITUTE-OF-MENTAL-HEALTH SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article; Proceedings Paper CT Satellite Symposium on Imaging Techniques, at the American-Society-for-Cell-Biology Meeting CY NOV 11, 1993 CL NEW ORLEANS, LA SP AMER SOC CELL BIOL DE BRAIN; BEHAVIORAL SCIENCE; MENTAL HEALTH; TECHNOLOGY RESEARCH ID HUMAN GENOME PROJECT AB The National Institute of Mental Health recognizes the importance that creative development of technology and methodology play in brain and behavioral science research. This institute is making major efforts to support such development through specific initiatives, like the Human Brain Project, In addition, this Institute is actively building bridges between business and academic research communities to make optimal use of funds for the research and development of commercially viable technologies relevant to all aspects of the Institute's mission through the Small Business Innovation Research and Small Business Technology Transfer Programs. Together, these efforts will culminate in a more vigorous scientific enterprise, and ultimately benefit the entire mental health community and society. RP HUERTA, MF (reprint author), NIMH,DIV NEUROSCI & BEHAV SCI,ROOM 11-103,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 8 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT PY 1994 VL 54 IS 2 BP 261 EP 267 DI 10.1016/0165-0270(94)90198-8 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PQ179 UT WOS:A1994PQ17900012 PM 7869757 ER PT J AU CHARNAS, L AF CHARNAS, L TI MYOSITIS ASSOCIATED WITH GROWTH-HORMONE THERAPY SO JOURNAL OF PEDIATRICS LA English DT Letter RP CHARNAS, L (reprint author), NICHHD, BETHESDA, MD 20892 USA. NR 0 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 OCT PY 1994 VL 125 IS 4 BP 671 EP 671 DI 10.1016/S0022-3476(94)70040-0 PG 1 WC Pediatrics SC Pediatrics GA PK529 UT WOS:A1994PK52900034 ER PT J AU YUAN, JH GOEHL, TJ HONG, L CLARK, J MURRILL, E MOORE, R AF YUAN, JH GOEHL, TJ HONG, L CLARK, J MURRILL, E MOORE, R TI TOXICOKINETICS OF OXAZEPAM IN RATS AND MICE SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID DISPOSITION AB The comparative toxicokinetics of oxazepam were studied in F344 rats, B6C3F1 mice, and Swiss-Webster mice of both sexes after an iv dose of 20 mg/kg and oral gavage doses of 50, 200, and 400 mg/kg. In addition, the toxicokinetics of oxazepam in a 3-week dosed-feed study of male B6C3F1 mice at 125 and 2500 ppm were also investigated. Results indicated that the elimination of oxazepam from plasma after iv injection in both rats and mice were first-order and could be best described by a two-compartment model with a terminal elimination half-life of 4-5 h for rats and 5-7 h for mice. After oral gavage dosing the peak oxazepam plasma concentrations in most rodents were reached within 2-3.5 h. At all doses studied, female rodents had significantly higher plasma concentrations than males. Absorption of oxazepam was significantly extended at higher oral doses of 200 and 400 mg/kg. At 50 mg/kg, the bioavailability of oxazepam in rats (<50%) was lower than in Swiss-Webster mice (>80%). The bioavailability of oxazepam in both B6C3F1 and Swiss-Webster mice decreased with increasing dose. A dose proportionality of C-max was not observed in rats and mice after gavage doses of 50, 200, and 400 mg/kg. Plasma concentrations of oxazepam in the dosed-feed study increased with the concentration of oxazepam in the feed, a quasi-steady-state of plasma concentrations of oxazepam was reached after approximately 4 days ad libitum exposure. In B6C3F1 mice, the estimated relative bioavailability of oxazepam from dosed feed (relative to gavage study at 50 mg/kg) was about 43%. C1 MIDWEST RES INST,KANSAS CITY,MO 64110. NIEHS,RES TRIANGLE PK,NC 27709. NR 18 TC 11 Z9 11 U1 0 U2 0 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD OCT PY 1994 VL 83 IS 10 BP 1373 EP 1379 DI 10.1002/jps.2600831002 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA PK992 UT WOS:A1994PK99200001 PM 7884653 ER PT J AU WEISS, GH GOANS, RE GITTERMAN, M ABRAMS, SA VIEIRA, NE YERGEY, AL AF WEISS, GH GOANS, RE GITTERMAN, M ABRAMS, SA VIEIRA, NE YERGEY, AL TI A NON-MARKOVIAN MODEL FOR CALCIUM KINETICS IN THE BODY SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE CALCIUM KINETICS; BONE ID BONE CALCIUM; BINDING AB We present a new generalized compartmental model for calcium kinetics as measured by tracer concentration in blood plasma. The parameter measuring incorporation of calcium in bone discriminates between different levels of physical development in female teenagers and between teenagers and adults. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX 77030. RP WEISS, GH (reprint author), NATL INST HLTH,DCRT,PHYS SCI LAB,BETHESDA,MD 20892, USA. OI Abrams, Steven/0000-0003-4972-9233 NR 19 TC 16 Z9 16 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD OCT PY 1994 VL 22 IS 5 BP 367 EP 379 DI 10.1007/BF02353861 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QT172 UT WOS:A1994QT17200002 PM 7791037 ER PT J AU PRESTON, KL BIGELOW, GE AF PRESTON, KL BIGELOW, GE TI DRUG DISCRIMINATION ASSESSMENT OF AGONIST-ANTAGONIST OPIOIDS IN HUMANS - A 3-CHOICE SALINE-HYDROMORPHONE-BUTORPHANOL PROCEDURE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID STIMULUS PROPERTIES; ABUSE LIABILITY; PRECIPITATED WITHDRAWAL; DEPENDENT HUMANS; HUMAN VOLUNTEERS; MIXED AGONIST; PENTAZOCINE; NALBUPHINE; EFFICACY; MORPHINE AB To assess the discriminative stimulus properties of mixed agonist-antagonist opioids in humans, postaddict volunteers were trained in a three-choice drug discrimination procedure to discriminate among the effects of saline (4 ml i.m.), hydromorphone (3 mg i.m.) and butorphanol (6 mg i.m.). Subjects earned monetary reinforcement by correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were concurrently collected. After training, generalization curves for hydromorphone, butorphanol, pentazocine, nalbuphine and buprenorphine were determined. In generalization testing, both hydromorphone and butorphanol produced dose-related increases in hydromorphone-appropriate and butorphanol-appropriate responses, respectively, and other characteristic subjective effect measures. Nalbuphine produced dose-related increases in discrimination as butorphanol and in those subjective effect measures increased by butorphanol. Buprenorphine produced dose-related increases in discrimination as hydromorphone and in those subjective effect measures increased by hydromorphone. Pentazocine was not consistently discriminated as either butorphanol or hydromorphone. These results differ from those of previous discrimination studies using similar methods but different training drugs. Compared to a previous study in which pentazocine served as the kappa-like training drug, the use as a training drug of the more pharmacologically specific kappa-like drug butorphanol permitted greater differentiation among test drugs and yielded discrimination results more consistent with other pharmacological evidence (buprenorphine being mu-like and nalbuphine being kappa-like). There was a close relationship between results of the discrimination measures and the subjective effect measures. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD. NATL INST DRUG ABUSE,INTRAMURAL RES PROGRAM,BALTIMORE,MD. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [DA-04089, DA-00050] NR 43 TC 35 Z9 35 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 OCT PY 1994 VL 271 IS 1 BP 48 EP 60 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PN490 UT WOS:A1994PN49000008 PM 7525929 ER PT J AU AULAKH, CS MAZZOLAPOMIETTO, P HILL, JL MURPHY, DL AF AULAKH, CS MAZZOLAPOMIETTO, P HILL, JL MURPHY, DL TI ROLE OF VARIOUS 5-HT RECEPTOR SUBTYPES IN MEDIATING NEUROENDOCRINE EFFECTS OF 1-(2,5-DIMETHOXY-4-METHYLPHENYL)-2-AMINOPROPANE (DOM) IN RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GROWTH-HORMONE; SEROTONIN AGONISTS; CORTICOSTERONE; ACTIVATION; BINDING; PLASMA; INVOLVEMENT; RADIOLIGAND; STIMULATION; SECRETION AB The phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats. Pretreatment with metergoline (serotonin, 5-HT1/5-HT2 antagonist), ritanserin and mianserin (5-HT2A/5-HT2C antagonists) significantly attenuated DOM-induced increases in prolactin, ACTH and corticosterone, whereas mesulergine (5-HT2A/5-HT2C antagonist) pretreatment significantly attenuated DOM-induced increases in plasma prolactin and ACTH but not corticosterone. Pretreatment with propranolol (beta adrenoceptor antagonist that also has high binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 and ondansetron (5-HT3 antagonists) attenuated DOM's effect on plasma prolactin, but did not attenuate DOM-induced increases in either ACTH or corticosterone. On the other hand, spiperone (5-HT1A/5-HT2A/D-2 antagonist) pretreatment significantly attenuated DOM-induced increases in ACTH but not corticosterone. These findings demonstrate involvement of 5-HT2A/5-HT2C and 5-HT3 receptors in mediating DOM-induced increases in plasma prolactin, whereas DOM-induced increases in ACTH appear to be mediated by stimulation of 5-HT2A receptors. DOM-induced corticosterone secretion appears to be mediated by stimulation of 5-HT2A and/or 5-HT2C receptors. DOM does not affect growth hormone secretion in rats. RP AULAKH, CS (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 9 Z9 9 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 OCT PY 1994 VL 271 IS 1 BP 143 EP 148 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PN490 UT WOS:A1994PN49000019 PM 7965707 ER PT J AU FAN, P VISENTIN, S WEIGHT, FF AF FAN, P VISENTIN, S WEIGHT, FF TI EFFECTS OF COCAINE ON THE SEROTONIN-INDUCED INWARD CURRENT IN RAT NODOSE GANGLION NEURONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID 5-HT3 RECEPTOR ANTAGONISTS; BINDING; BLOCKADE; IDENTIFICATION; PHARMACOLOGY; TRANSPORTERS; (-)-COCAINE; DOPAMINE; LIGAND; CELLS AB Application of 5-hydroxytryptamine (5-HT) to freshly isolated rat nodose ganglion neurons produced a fast inward current when measured using the whole-cell patch-clamp technique. This current was blocked by the 5-HT3 receptor antagonist MDL72222. The selective 5-HT3 receptor agonist 2-methyl-5-HT induced a similar current. Cocaine (0.1-300 mu M) applied simultaneously with 5-HT (0.25-50 mu M) inhibited the 5-HT-induced current. The inhibition did not appear to be voltage dependent. If cocaine was preapplied for about 30 sec, the effect of cocaine on 5-HT current was increased. Both the peak and the steady-state 5-HT current was depressed by cocaine. However, the peak current was more sensitive to cocaine than the steady-state current. The concentration-response curves of cocaine in different agonist concentrations revealed that cocaine competitively inhibited the 5-HT3 receptor-mediated current with a pA(2) value of 5.8 and an apparent K-D of 1.6 mu M. These results suggest that in addition to the other well known mechanisms, the 5-HT3 receptor-ion channel complex is another site for cocaine action. RP FAN, P (reprint author), NIAAA,CELLULAR & MOLEC NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Visentin, Sergio/G-9779-2016 OI Visentin, Sergio/0000-0001-8510-6987 NR 32 TC 9 Z9 9 U1 2 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 OCT PY 1994 VL 271 IS 1 BP 262 EP 266 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PN490 UT WOS:A1994PN49000034 PM 7965723 ER PT J AU SHAYANI, V NEWMAN, KD DICHEK, DA AF SHAYANI, V NEWMAN, KD DICHEK, DA TI OPTIMIZATION OF RECOMBINANT T-PA SECRETION FROM SEEDED VASCULAR GRAFTS SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID EXPANDED POLYTETRAFLUOROETHYLENE GRAFTS; MODIFIED ENDOTHELIAL-CELLS; MEDIATED GENE-TRANSFER; PLASMINOGEN-ACTIVATOR; ARTERIAL PROSTHESES; SHEAR-STRESS; SAPHENOUS-VEIN; FLOW; COAGULATION; THROMBOSIS AB Seeding of vascular grafts with genetically engineered endothelial cells (EC) secreting anticoagulant or fibrinolytic agents offers a potential means of improving patency rates. Prior to the initiation of in vivo studies, we examined cell retention and tissue plasminogen activator (t-PA) secretion from small-diameter synthetic graft segments seeded with sheep venous EC genetically engineered to secrete human t-PA. Following retroviral-mediated gene transfer, EC were seeded at varying densities onto 4-mm-diameter synthetic graft segments of different composition, achieving confluent coverage of all materials. t-PA production from seeded grafts was evaluated under both static conditions and after flow exposure, for up to 3 days after seeding. t-PA secretion varied directly with increasing seeding density for all graft types, reaching a maximum of 20 ng/cm(2)/24 hr. t-PA secretion correlated highly with the number of seeded cells as determined by measurement of DNA from lysates of seeded grafts (r(2) = 0.90, P < 0.0001). For all graft types tested, approximately 50% of seeded cells were retained after exposure to flow in vitro. Retained EC remained viable as determined by t-PA secretion. The rate of t-PA secretion from collagen-impregnated Dacron grafts was higher than that obtained with other materials both under static conditions and after flow exposure. This higher rate was most likely due to the higher surface area presented by the Dacron grafts. These data demonstrate that small-diameter prosthetic graft materials can be coated with a layer of EC that (i) remains metabolically active and capable of secreting a fibrinolytic agent, and (ii) remains adherent to the graft surface after exposure to flow. These experiments provide a foundation for in vivo studies in which grafts are seeded with EC genetically engineered to increase local fibrinolysis. (C) 1994 Academic Press, Inc. C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. CHILDRENS NATL MED CTR,DEPT SURG,WASHINGTON,DC 20052. RP SHAYANI, V (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 41 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 1994 VL 57 IS 4 BP 495 EP 504 DI 10.1006/jsre.1994.1175 PG 10 WC Surgery SC Surgery GA PL711 UT WOS:A1994PL71100010 PM 7934027 ER PT J AU IWASA, KH AF IWASA, KH TI A MEMBRANE MOTOR MODEL FOR THE FAST MOTILITY OF THE OUTER HAIR CELL SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MECHANICAL RESPONSES; FORCE GENERATION; SHAPE CHANGES; CAPACITANCE AB A model is presented for describing the membrane potential-dependent motility of the outer hair cell. This model assumes that the motility is due to conformational changes of motor molecules in the plasma membrane. Two kinds of experimental observations, elasticity of the cell and stretch dependence of the motor molecule, are important for characterize this motility by the model. The motor molecule can be described by a two-state model which has electrical and mechanical components in the free energy. The electrical component is due to the charge transferred across the membrane and the mechanical component is due to a change in membrane area in the two states. It can be shown that the elastic element and the motor element are connected in series. Thus the apparent strain of the cell is represented by the sum of true elastic strain and changes due to motor molecules, This model predicts the amplitude of the movement and the force produced by the motility. The model predicts the force produced under isometric condition is about 0.1 nN/mV, in agreement with values estimated from in vivo conditions. The effect of an elastic load attached to the cell is also discussed. RP IWASA, KH (reprint author), NIDCD,CELLULAR BIOL LAB,BIOPHYS SECT,NIH BLDG 9,RM 1E120,MSC 0920,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 18 TC 95 Z9 96 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 1994 VL 96 IS 4 BP 2216 EP 2224 DI 10.1121/1.410094 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA PL708 UT WOS:A1994PL70800026 PM 7963034 ER PT J AU ALTURA, BT ALTURA, BM BIRCH, NJ DUTTA, SK ELIN, R FLODIN, N FRANZ, KB HENRIQUEZ, S HOLDEN, M KAMINSKI, MV KOZINN, P LEHR, D LIFSHITZ, F MAGUIRE, ME MIMOUNI, FB PRASAD, AS SEELIG, BJ SEELIG, CB SPENCER, H TSANG, RC WALLACH, S WOOD, TE AF ALTURA, BT ALTURA, BM BIRCH, NJ DUTTA, SK ELIN, R FLODIN, N FRANZ, KB HENRIQUEZ, S HOLDEN, M KAMINSKI, MV KOZINN, P LEHR, D LIFSHITZ, F MAGUIRE, ME MIMOUNI, FB PRASAD, AS SEELIG, BJ SEELIG, CB SPENCER, H TSANG, RC WALLACH, S WOOD, TE TI TRIBUTE TO SEELIG,MILDRED SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Item About an Individual C1 UNIV WOLVERHAMPTON,WOLVERHAMPTON,W MIDLANDS,ENGLAND. UNIV MARYLAND,DIV GASTROENTEROL,COLLEGE PK,MD 20742. NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. UNIV SO ALABAMA,DEPT BIOCHEM,MOBILE,AL. BRIGHAM YOUNG UNIV,PROVO,UT 84602. FREEMAN UNIV HOSP,NEWCASTLE TYNE,TYNE & WEAR,ENGLAND. THOREK MED CTR,CHICAGO,IL. WESTCHESTER CTY MED CTR,VALHALLA,NY. MAIMONIDES HOSP,DEPT PEDIAT,BROOKLYN,NY. CASE WESTERN RESERVE UNIV,DEPT PHARMACOL,CLEVELAND,OH 44106. UNIV DETROIT,CTR HLTH,DETROIT,MI 48221. EMORY UNIV,SCH MED,OUTPATIENT PSYCHOTHERAPY TRAINING PROGRAM,ATLANTA,GA. UNIV N CAROLINA,AMBULATORY SERV,CHAPEL HILL,NC. LOYOLA UNIV,SCH MED,CHICAGO,IL 60611. PERINATAL RES INST,CINCINNATI,OH. RP ALTURA, BT (reprint author), SUNY HLTH SCI CTR,DEPT PHYSIOL,450 CALRKSON AVE,BROOKLYN,NY 11203, USA. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 13 IS 5 BP 401 EP 407 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PK985 UT WOS:A1994PK98500001 ER PT J AU ELIN, RJ HOSSEINI, JM GILL, JR AF ELIN, RJ HOSSEINI, JM GILL, JR TI ERYTHROCYTE AND MONONUCLEAR BLOOD-CELL MAGNESIUM CONCENTRATIONS ARE NORMAL IN HYPOMAGNESEMIC PATIENTS WITH CHRONIC RENAL MAGNESIUM WASTING SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE MAGNESIUM; BARTTERS SYNDROME; TUBULOPATHY; SERUM; ERYTHROCYTES; MONONUCLEAR BLOOD CELLS ID BARTTERS-SYNDROME; DEFICIENCY; BODY; RATS AB Objective: The purpose of this study was to determine the plasma, erythrocyte, and mononuclear blood cell (MBC) magnesium concentrations in patients with chronic, severe hypomagnesemia due to a chronic magnesium-wasting tubulopathy. Methodology: Six patients with Bartter's syndrome and five patients with magnesium-wasting tubulopathy were compared with normal subjects. We determined magnesium in plasma, erythrocytes, and MBCs. Results: Patients with chronic magnesium-wasting tubulopathy had a significantly lower plasma magnesium concentration than controls, but erythrocyte magnesium concentration and MBC magnesium concentration and content did not differ significantly between patients and controls. Conclusion: Two disorders with chronic magnesium-wasting tubulopathies are associated with a low plasma magnesium concentration but normal erythrocyte and MBC magnesium. C1 NHLBI,BETHESDA,MD 20892. RP ELIN, RJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BLDG 10,ROOM 2C-306,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 5 Z9 6 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 OCT PY 1994 VL 13 IS 5 BP 463 EP 466 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PK985 UT WOS:A1994PK98500008 PM 7836624 ER PT J AU LEVINE, R AF LEVINE, R TI POSSIBLE ROLE OF SUPPLEMENTAL CALCIUM IN PREVENTING PREECLAMPSIA SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Meeting Abstract C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 13 IS 5 BP 531 EP 532 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PK985 UT WOS:A1994PK98500063 ER PT J AU BROWN, LJ DEPAOLA, DP DUGONI, AA NIESSEN, LC PRIDE, J AF BROWN, LJ DEPAOLA, DP DUGONI, AA NIESSEN, LC PRIDE, J TI SPOTLIGHT ON TODAYS MAJOR ISSUES - 5 SHARE THEIR VIEWS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 UNIV PACIFIC,SCH DENT,SAN FRANCISCO,CA 94115. BAYLOR COLL DENT,DEPT PUBL HLTH SCI,DALLAS,TX 75246. PRIDE INST,GREENBRAE,CA. RP BROWN, LJ (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1994 VL 125 IS 10 BP 1321 EP 1328 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PY411 UT WOS:A1994PY41100011 PM 7844296 ER PT J AU SNYDER, MP OBARZANEK, E MONTGOMERY, DH FELDMAN, H NICKLAS, T RAIZMAN, D RUPP, J BIGELOW, C LAKATOS, E AF SNYDER, MP OBARZANEK, E MONTGOMERY, DH FELDMAN, H NICKLAS, T RAIZMAN, D RUPP, J BIGELOW, C LAKATOS, E TI REDUCING THE FAT-CONTENT OF GROUND-BEEF IN A SCHOOL FOODSERVICE SETTING SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB Objective The objective was to develop and test the nutrient results of a two-step defatting procedure with ground beef in a school foodservice setting as part of the Eat Smart school lunch component of the Child and Adolescent Trial for Cardiovascular Health (CATCH). Setting and design The procedure was tested in a school foodservice setting to determine the effect of cooking, draining, and subsequent rinsing with hat water on nutrient composition of ground beef. Samples of raw; cooked and drained; and cooked, drained, and rinsed ground beef were collected and chemically analyzed for total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, iron, and niacin content. Results The results indicated that the total fat and the saturated, monounsaturated, and polyunsaturated fatty acids were significantly reduced 31% to 35% from cooking and draining (P<.005) and reduced by an additional 25% to 30% from rinsing (P<.0001). Cholesterol content was not affected. Iron content increased after the cooking and rinsing, although not significantly. Niacin content significantly decreased during rinsing by 28% (P<.005), but the mean value of the cooked, drained, and rinsed ground beef still met the criteria of the Food and Drug Administration for a good source of niacin. Application The two-step defatting procedure developed for use in a school foodservice setting lowers the total fat and saturated fatty acid content of ground beef without substantially reducing its nutritional quality. C1 NHLBI,BETHESDA,MD 20892. UNIV TEXAS,CTR HLTH PROMOT,AUSTIN,TX 78712. NEW ENGLAND RES INST,WATERTOWN,MA 02172. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA. TUFTS UNIV NEW ENGLAND MED CTR,FRANCES STERN NUTR CTR,NEW ENGLAND RES INST,BOSTON,MA. UNIV CALIF SAN DIEGO,DEPT FAMILY MED,SAN DIEGO,CA 92103. UNIV MASSACHUSETTS,DIV PUBL HLTH,AMHERST,MA 01003. SEARLE DRUG CO,SKOKIE,IL. RP SNYDER, MP (reprint author), UNIV MINNESOTA,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [U01HL 39870, U01HL 39852, U01HL 39927] NR 27 TC 18 Z9 18 U1 0 U2 0 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 OCT PY 1994 VL 94 IS 10 BP 1135 EP 1139 DI 10.1016/0002-8223(94)91133-9 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PK778 UT WOS:A1994PK77800011 PM 7930317 ER PT J AU ETTINGER, WH FRIED, LP HARRIS, T SHEMANSKI, L SCHULZ, R ROBBINS, J AF ETTINGER, WH FRIED, LP HARRIS, T SHEMANSKI, L SCHULZ, R ROBBINS, J TI SELF-REPORTED CAUSES OF PHYSICAL-DISABILITY IN OLDER-PEOPLE - THE CARDIOVASCULAR HEALTH STUDY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID IMPACT AB OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community dwelling older people. DESIGN: Cross sectional analyses of data obtained in an observational cohort study. SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA. PARTICIPANTS: 5201 community-dwelling people greater than or equal to 65 years old. RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status. CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27157. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV PITTSBURGH,UNIV CTR SOCIAL & URBAN RES,PITTSBURGH,PA. UNIV CALIF DAVIS,DEPT MED,DAVIS,CA 95616. RP ETTINGER, WH (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. NR 19 TC 193 Z9 195 U1 1 U2 7 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 OCT PY 1994 VL 42 IS 10 BP 1035 EP 1044 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PK179 UT WOS:A1994PK17900001 PM 7930326 ER PT J AU GURALNIK, JM AF GURALNIK, JM TI UNDERSTANDING THE RELATIONSHIP BETWEEN DISEASE AND DISABILITY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID FUNCTIONAL STATUS; ARTHRITIS RP GURALNIK, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,ROOM 3C-309,BETHESDA,MD 20892, USA. NR 13 TC 32 Z9 32 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 OCT PY 1994 VL 42 IS 10 BP 1128 EP 1129 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PK179 UT WOS:A1994PK17900016 PM 7930341 ER PT J AU SHARARA, FI BHARTIYA, D NIEMAN, LK AF SHARARA, FI BHARTIYA, D NIEMAN, LK TI GROWTH-HORMONE RECEPTOR GENE-EXPRESSION IN THE MOUSE UTERUS - MODULATION BY GONADAL-STEROIDS SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE GROWTH HORMONE; GROWTH HORMONE RECEPTOR; PCR; IN-SITU HYBRIDIZATION; UTERUS ID SERUM BINDING-PROTEIN; PROLACTIN RECEPTOR; RIBONUCLEIC-ACID; PROLIFERATION; PREGNANCY; UTERINE; FAMILY; CELLS; RAT AB Objectives: We hypothesized that the mouse uterus expresses a growth hormone receptor (GHR) and that mouse endometrial GHR mRNA may undergo in vivo regulation by estradiol (E2) and progesterone (P). Methods: Two weeks after bilateral ovariectomy, 35-day-old Balb/c mice were randomly assigned to receive either vehicle injections; E2 priming (300 ng/day) on days 1-6 and E2 (50 ng/day) on day 11; P (1 mg/day) on days 8-11; or E2 priming with P (days 8-11) and E2 on day 11, with or without RU 486 on days 8-11. At sacrifice 24 hours after the last injection, the uteri were processed for RNA extraction and in situ hybridization for GHR mRNA. Reverse transcriptase polymerase chain reaction amplification of uterine mRNA was performed to establish whether treatment with gonadal steroids differentially affected GHR gene expression. The GHR primers flanked a 326-bp region from the intracellular domain sharing no homology to the prolactin receptor or to the GH-binding protein. A 48-bp digoxigenin-labeled oligoprobe was used for in situ hybridization. Results: Densitometry analysis of polymerase chain reaction products from total uterine mRNA revealed similar GHR mRNA expression in vehicle- and estrogen-treated animals. The addition of progesterone reduced GHR mRNA expression. In situ hybridization localized the GHR mRNA to the endometrium, glands, stroma, and myometrium. Stromal staining was reduced in the progesterone-treated mice. Conclusions: The identification of GHR message suggests that the mouse uterus is a site of action of GH. The lack of modulation of epithelial GHR by sex steroids does not support a role of GHR in this compartment. C1 NICHHD,DEB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 0N-262,BETHESDA,MD 20892. NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD OCT-DEC PY 1994 VL 1 IS 4 BP 285 EP 289 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QG066 UT WOS:A1994QG06600007 PM 9419785 ER PT J AU PASS, HI POGREBNIAK, HW AF PASS, HI POGREBNIAK, HW TI POTENTIAL USES OF PROSTAGLANDIN E(1) ANALOG FOR CARDIOVASCULAR-DISEASE SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Letter ID MISOPROSTOL; HEART RP PASS, HI (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 1994 VL 108 IS 4 BP 789 EP 790 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PK514 UT WOS:A1994PK51400031 PM 7934121 ER PT J AU SHILYANSKY, J WILSON, W TEMECK, BK PASS, HI AF SHILYANSKY, J WILSON, W TEMECK, BK PASS, HI TI PULMONARY ARTERY-BRONCHIAL FISTULA DURING LYMPHOMA TREATMENT SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Letter C1 NCI,MED ONCOL BRANCH,BETHESDA,MD 20892. RP SHILYANSKY, J (reprint author), NCI,THORAC ONCOL SECT,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 1994 VL 108 IS 4 BP 790 EP 791 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PK514 UT WOS:A1994PK51400032 PM 7934122 ER PT J AU RACE, RE ERNST, D SUTTON, D AF RACE, RE ERNST, D SUTTON, D TI SEVERE AUTOLYSIS DOES NOT PREVENT SCRAPIE DIAGNOSIS IN SHEEP SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Note RP RACE, RE (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI COLUMBIA PA PO BOX 6023, COLUMBIA, MO 65205 SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD OCT PY 1994 VL 6 IS 4 BP 486 EP 489 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA PN460 UT WOS:A1994PN46000015 PM 7858030 ER PT J AU PIRAS, G KASHANCHI, F RADONOVICH, MF DUVALL, JF BRADY, JN AF PIRAS, G KASHANCHI, F RADONOVICH, MF DUVALL, JF BRADY, JN TI TRANSCRIPTION OF THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I PROMOTER BY AN ALPHA-AMANITIN-RESISTANT POLYMERASE SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; TATA-BINDING PROTEIN; TROPICAL SPASTIC PARAPARESIS; EUKARYOTIC RNA-POLYMERASES; COLONY-STIMULATING FACTOR; RECEPTOR GENE-EXPRESSION; HORMONE-RELATED PROTEIN; HUMAN U6 GENE; LEUKEMIA-VIRUS; III TRANSCRIPTION AB The human T-lymphotropic virus type I (HTLV-I) promoter contains the structural features of a typical RNA polymerase II (pol II) template. The promoter contains a TATA box 30 bp upstream of the transcription initiation site and binding sites for several pol II transcription factors, and long poly(A)(+) RNA is synthesized from the integrated HTLV-I proviral DNA in vivo. Consistent with these characteristics, HTLV-I transcription activity was reconstituted in vitro by using TATA-binding protein, TFIIA, recombinant TFIIB, TFIIE, and TFIIF, TFIIH, and pol II. Transcription of the HTLV-I promoter in the reconstituted system requires RNA pol II. In HeLa whole cell extracts, however, the HTLV-I long terminal repeat also contains an overlapping transcription unit (OTU). HTLV-I OTU transcription is initiated at the same nucleotide site as the RNA isolated from the HTLV-I-infected cell line MT-2 but was not inhibited by the presence of cu-amanitin at concentrations which inhibited the adenovirus major late pol II promoter (6 mu g/ml). HTLV-I transcription was inhibited when higher concentrations of cx-amanitin (60 mu g/ml) were used, in the range of a typical pol III promoter (VA-I). Neutralization and depletion experiments with three distinct pol II antibodies demonstrate that RNA pol II is not required for HTLV-I OTU transcription. Antibodies to basal transcription factors TATA-binding protein and TFIIB, but not TFIIIC, inhibited HTLV-I OTU transcription. These observations suggest that the HTLV-I long terminal repeat contains overlapping promoters, a typical pol II promoter and a unique pol III promoter which requires a distinct set of transcription factors. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 99 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1994 VL 68 IS 10 BP 6170 EP 6179 PG 10 WC Virology SC Virology GA PG541 UT WOS:A1994PG54100004 PM 7521915 ER PT J AU MAURY, W AF MAURY, W TI MONOCYTE MATURATION CONTROLS EXPRESSION OF EQUINE INFECTIOUS-ANEMIA VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD MONOCYTES; LONG TERMINAL REPEAT; NF-KAPPA-B; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; LENTIVIRUS INFECTIONS; TISSUE MACROPHAGES; NUCLEAR FACTOR; CELL TROPISM AB In vivo, equine infectious anemia virus (EIAV) replicates in tissues rich in macrophages, and it is widely believed that the tissue macrophage is the principal, if not sole, cell within the host that replicates virus. No viral replication has been detected in circulating peripheral blood monocytes. However, proviral DNA can be detected in these cells, and monocytes may serve as a reservoir for the virus. In this study, an in vitro model was developed to clarify the role of monocyte maturation in regulating EIAV expression. Freshly isolated, nonadherent equine peripheral blood monocytes were infected,vith a macrophage-tropic strain of EIAV, and expression of EIAV was monitored in cells held as nonadherent monocytes and cells allowed to adhere and differentiate into macrophages. A 2- to 3-day delay in viral antigen expression was observed in the nonadherent cells. This restriction of viral expression in monocytes was supported by nuclear run-on studies demonstrating that on day 5 postinfection, the level of actively transcribed viral messages was 4.7-fold lower in monocyte cultures than in macrophage cultures. Electrophoretic mobility shift assays identified three regions of the U3 enhancer that interacted,vith nuclear extracts from normal equine macrophages. Each region contained the core binding motif of a family of transcription factors that includes the product of the proto oncogene ets. Antibodies to the Ets family member PU.1 caused a supershifting of retarded bands in an electrophoretic mobility shift assay. Transfection studies of ets motif mutants demonstrated that the U3 ets sites were important in the regulation of EIAV transcription in macrophages. Interactions between the ets motif and nuclear extracts from freshly isolated, nonadherent monocytes, macrophages adherent for 1 or 2 days, or macrophages adherent for 5 days gave different patterns of retarded bands, although the binding specificities were similar with all three extracts. The different complexes formed by monocyte and macrophage nuclear extracts may explain the enhanced ability of mature macrophages to support EIAV expression. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 59 TC 62 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1994 VL 68 IS 10 BP 6270 EP 6279 PG 10 WC Virology SC Virology GA PG541 UT WOS:A1994PG54100015 PM 8083967 ER PT J AU MILLER, CJ MARTHAS, M TORTEN, J ALEXANDER, NJ MOORE, JP DONCEL, GF HENDRICKX, AG AF MILLER, CJ MARTHAS, M TORTEN, J ALEXANDER, NJ MOORE, JP DONCEL, GF HENDRICKX, AG TI INTRAVAGINAL INOCULATION OF RHESUS MACAQUES WITH CELL-FREE SIMIAN IMMUNODEFICIENCY VIRUS RESULTS IN PERSISTENT OR TRANSIENT VIREMIA SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-INFECTION; GENITAL TRANSMISSION; LYMPHOID-TISSUES; HOMOSEXUAL MEN; SIV; LOCALIZATION; MONKEYS; DISEASE; TYPE-1; NONOXYNOL-9 AB The simian immunodeficiency virus (SN)-rhesus macaque model of heterosexual human immunodeficiency virus transmission consists of atraumatic application of cell-free SIVmac onto the intact vaginal mucosa of mature female rhesus macaques. This procedure results in systemic infection, and eventually infected animals develop the clinical signs and pathologic changes of simian AIDS. To achieve 100% transmission with the virus stocks used to date, multiple intravaginal inoculations are required. The current titration study utilized two stocks of SIVmac and demonstrated that a single intravaginal dose of cell-free SIV can reliably produce infection in rhesus macaques. This study also demonstrated that some animals intravaginally inoculated with cell-free SIVmac develop transient viremia characterized by a limited ability to isolate virus from peripheral blood mononuclear cells and lymph node mononuclear cells and no seroconversion to SIV antigen. SIV could be isolated from the peripheral lymph nodes of transiently viremic animals only during periods of viremia and not at times when SIV was not detected in circulating mononuclear cells. Thus, peripheral lymphoid tissues were not reservoirs of infection in the transiently viremic animals. Taken together, these results suggest either that the SIV infection was cleared in the transiently viremic animals or that SIV infection is limited to a compartment of the genital mucosal immune system that cannot be assessed by monitoring SIV infection in peripheral blood mononuclear cells and peripheral lymphoid tissue. C1 UNIV CALIF DAVIS,SCH VET MED,DEPT VET PATHOL MICROBIOL & IMMUNOL,DAVIS,CA 95616. NICHHD,BETHESDA,MD 20892. AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10018. NYU,SCH MED,NEW YORK,NY 10018. EASTERN VIRGINIA MED SCH,DEPT OBSTET & GYNECOL,CONTRACEPT RES & DEV PROGRAM,NORFOLK,VA 23507. RP MILLER, CJ (reprint author), UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616, USA. FU NIAID NIH HHS [AI31383, AI35545, AI36082] NR 38 TC 163 Z9 163 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1994 VL 68 IS 10 BP 6391 EP 6400 PG 10 WC Virology SC Virology GA PG541 UT WOS:A1994PG54100027 PM 8083977 ER PT J AU KIM, WK TANG, Y KENNY, JJ LONGO, DL MORSE, HC AF KIM, WK TANG, Y KENNY, JJ LONGO, DL MORSE, HC TI IN MURINE AIDS, B-CELLS ARE EARLY TARGETS OF DEFECTIVE VIRUS AND ARE REQUIRED FOR EFFICIENT INFECTION AND EXPRESSION OF DEFECTIVE VIRUS IN T-CELLS AND MACROPHAGES SO JOURNAL OF VIROLOGY LA English DT Note ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CYTOKINE GENES; SYNDROME MAIDS; MICE; MODEL; MOUSE; INDUCTION; LINEAGE AB Previous studies showed that B cells and CD4(+) T cells are required for induction of a murine retrovirus-induced immunodeficiency syndrome, murine AIDS. Using B6 mice deficient in mature B cells as a result of a knockout of the transmembrane exon of the immunoglobulin M gene, we found that spleen and other tissues from murine AIDS virus-infected mice did not express the defective virus (BM5def) required for induction of disease, even though helper viruses were readily detectable and BM5def proviral DNA was present. This indicates that the B-lineage cells are the primary targets for infection and expression of the defective virus and that in the absence of mature B cells, there is inefficient infection of T cells and macrophages. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-72663] NR 20 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1994 VL 68 IS 10 BP 6767 EP 6769 PG 3 WC Virology SC Virology GA PG541 UT WOS:A1994PG54100068 PM 8084011 ER PT J AU AGUILERA, G KAPUR, S FEUILLAN, P SUNARAKBASAK, B BATHIA, AJ AF AGUILERA, G KAPUR, S FEUILLAN, P SUNARAKBASAK, B BATHIA, AJ TI DEVELOPMENTAL-CHANGES IN ANGIOTENSIN-II RECEPTOR SUBTYPES AND AT(1) RECEPTOR MESSENGER-RNA IN RAT-KIDNEY SO KIDNEY INTERNATIONAL LA English DT Article ID MESANGIAL CELLS; GENE-EXPRESSION; GROWTH-FACTOR; RENAL GROWTH; RENIN; FETUS; REVEALS; SYSTEM; PROLIFERATION; CLONING AB The changes in angiotensin II receptor subtypes, type 1 (AT(1)) and type 2 (AT(2)) binding, and AT(1) mRNA levels during development were studied in the rat kidney using autoradiographic and in situ hybridization techniques. Autoradiographic analysis of I-125-[Sar(1), Ile(8)]Ang II binding to slide-mounted kidney sections from 2 and 5 day-old rats discerned AT(2) binding sites associated with advancing tubules and ampullae of the ureteric bud, and in the metanephric mass in the nephrogenic zone of the cortex. AT(1) binding was present in the metanephric mass and immature glomeruli on days 2, 5 and 7 after birth. Differentiating and mature kidneys of 14-day, 21-day and 14-week old adult rats had solely AT(1) receptor binding over glomeruli in renal cortex and in the inner stripe of the outer medulla. AT(1) mRNA was expressed discretely as early as 2 days of age in the immature glomeruli and in a diffuse radiating pattern in the renal cortex. In the medulla, AT(1) receptor mRNA expression appeared discretely on day 7 and reached peak levels on day 21 in the inner stripe of the outer medulla. The data indicate that AT(1) receptor mRNA is developmentally regulated in rat kidney and its expression in the cortex precedes that of AT(1) receptor ligand binding. The temporal pattern of expression of binding for both receptor subtypes suggests that while AT(2) receptors may be involved in cell proliferation and early differentiation of the nephron, AT(1) receptors have a dual role, early in nephron differentiation and later in development in renal function. C1 GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC. RP AGUILERA, G (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BLDG 10,RM 10N262,BETHESDA,MD 20892, USA. NR 51 TC 65 Z9 67 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1994 VL 46 IS 4 BP 973 EP 979 DI 10.1038/ki.1994.356 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PH786 UT WOS:A1994PH78600003 PM 7861723 ER PT J AU WOJNICKI, FHE BACHER, JD GLOWA, JR AF WOJNICKI, FHE BACHER, JD GLOWA, JR TI USE OF SUBCUTANEOUS VASCULAR ACCESS PORTS IN RHESUS-MONKEYS SO LABORATORY ANIMAL SCIENCE LA English DT Article ID CHAIR RESTRAINT; INDIVIDUAL VULNERABILITY; NONHUMAN-PRIMATES; TETHERING SYSTEM; INFUSION; MACAQUES; VEST AB To investigate new approaches for treatment of drug abuse, subcutaneous vascular ports were implanted in rhesus monkeys ((Macaca mulatta) for use in drug self-administration studies. Internal or external jugular veins were cannulated, and the catheter was attached to a subcutaneous port that was positioned on the back between the shoulder blades. This port/catheter system allowed easy serial blood sampling and intravenous drug administration. Daily use of the ports in awake monkeys was simple, effective, and caused no apparent stress over a 2-h experimental session. At the time of submission(1), the mean functional lifetime of the port/catheter system in 20 monkeys implanted longer than 6 months was 243.61 days, with the upper range being 540 days. Several complications developed with this system, and solutions to these problems are described. With proper aseptic use, the subcutaneous vascular port system provided a safe and enduring method for daily access for intravenous sampling and/or drug delivery The duration of the preparation is a considerable improvement compared with exteriorized catheterization. C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NCRR,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 19 TC 45 Z9 45 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1994 VL 44 IS 5 BP 491 EP 494 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA PP079 UT WOS:A1994PP07900012 PM 7844959 ER PT J AU HARALABOPOULOS, GC GRANT, DS KLEINMAN, HK LELKES, PI PAPAIOANNOU, SP MARAGOUDAKIS, ME AF HARALABOPOULOS, GC GRANT, DS KLEINMAN, HK LELKES, PI PAPAIOANNOU, SP MARAGOUDAKIS, ME TI INHIBITORS OF BASEMENT-MEMBRANE COLLAGEN-SYNTHESIS PREVENT ENDOTHELIAL-CELL ALIGNMENT IN MATRIGEL IN-VITRO AND ANGIOGENESIS IN-VIVO SO LABORATORY INVESTIGATION LA English DT Article DE COLLAGEN INHIBITORS; MATRIX; NEOVASCULARIZATION; BLOOD VESSELS; DIFFERENTIATION ID LAMININ-A-CHAIN; CAPILLARY-LIKE STRUCTURES; TUMOR-GROWTH; PHENOTYPIC MODULATION; EXTRACELLULAR-MATRIX; IV COLLAGEN; DIFFERENTIATION; IDENTIFICATION; PEPTIDE; BIOSYNTHESIS AB BACKGROUND: The formation of a basement membrane is the last step in the development of a new blood vessel. Matrigel, a laminin-rich reconstituted basement membrane matrix induces the differentiation of endothelial cells into capillary-like structures. EXPERIMENTAL DESIGN: The effect of inhibitors of basement membrane collagen synthesis, tricyclodecan-9-yl xanthate (D609) and 8,9-dihydroxy-7-methyl-benzo[b] quinolizinium bromide (GPA 1734), was investigated on endothelial cell tube formation on Matrigel in vitro and in an angiogenesis assay in C57 black mice in vivo. RESULTS: D609 and GPA 1734 caused a dose-dependent decrease in tube formation in vitro with complete inhibition at 50 mu g/ml for D609 and 15 mu g/ml for GPA 1734. The inhibitory effect an capillary tube formation by both agents was reversible. Tube formation correlated well with collagenous protein biosynthesis, Parallel studies on endothelial cells cultured on plastic indicate that cell viability, proliferation, attachment, and morphology were not affected by the presence of these collagen inhibitors at doses that blocked tube formation and collagen biosynthesis. D609 and GPA 1734 also inhibited endothelial cell infiltration in response to SIKVAV in an in vivo angiogenesis model system. CONCLUSIONS: These results indicate that newly synthesised collagen is a prerequisite for expression of the endothelial cell phenotype for tube formation and that prevention of collagenous protein biosynthesis inhibits tube formation and angiogenesis in vivo. C1 UNIV PATRAS,SCH MED,DEPT PHARMACOL,GR-26110 PATRAI,GREECE. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. UNIV WISCONSIN,SINAI SAMARITAN MED CTR,DEPT MED,MILWAUKEE,WI 53201. UNIV PATRAS,SCH PHARM,DEPT MOLEC PHARMACOL,GR-26110 PATRAI,GREECE. NR 33 TC 63 Z9 65 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 1994 VL 71 IS 4 BP 575 EP 582 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PP786 UT WOS:A1994PP78600016 PM 7526036 ER PT J AU FELZMANN, T GISSLINGER, H LUDWIG, H AF FELZMANN, T GISSLINGER, H LUDWIG, H TI IMMUNOLOGICAL FINDINGS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME SO LEUKEMIA & LYMPHOMA LA English DT Review DE MYELODYSPLASTIC SYNDROMES; IMMUNOPHENOTYPING; FLOW CYTOMETRY; CYTOKINES AB Activation of monocytes and granulocytes in vitro by cytokines, in vivo administration of cytokines, as well as in vivo cytokine production due to infectious and inflammatory diseases causes changes of the surface expression density of certain membrane molecules. In recent studies we attempted to determine the feasibility of using flow cytometric immunophenotyping as a tool to develop a sensitive parameter for detecting infections at an early stage of disease when clinical parameters are still negative. Since infections are an important factor determining the clinical course of myelodysplastic syndromes (MDS), early detection of infection might be beneficial for these immunocompromised patients. We indeed found activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes of clinically infection free MDS patients suggesting enhanced immune activity in these patients, most likely due to latent or beginning infections. In particular, analyses of the expression density of receptors for IgG (Fc gamma Rs), complement receptors, and certain activation-associated surface molecules such as the CD67 and the M5 molecule seem to be of clinical relevance. We will also discuss findings concerning changes of cytokine levels and functional alterations of immunologic parameters in MDS patients. RP FELZMANN, T (reprint author), NCI,METAB BRANCH,CELLULAR IMMUNOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 6B05,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 1994 VL 15 IS 3-4 BP 201 EP 208 DI 10.3109/10428199409049716 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA PN901 UT WOS:A1994PN90100002 PM 7866269 ER PT J AU POMMIER, Y AF POMMIER, Y TI DNA TOPOISOMERASES - GENOME GATE-KEEPERS AND THEIR INTRUDERS, ANTICANCER AND ANTIBACTERIAL DRUGS SO M S-MEDECINE SCIENCES LA French DT Editorial Material RP POMMIER, Y (reprint author), NCI,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD OCT PY 1994 VL 10 IS 10 BP 953 EP 955 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PM680 UT WOS:A1994PM68000003 ER PT J AU WEN, H CHESNICK, AS BALABAN, RS AF WEN, H CHESNICK, AS BALABAN, RS TI THE DESIGN AND TEST OF A NEW VOLUME COIL FOR HIGH-FIELD IMAGING SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE 4T; HEAD; IMAGING; EFFICIENCY ID SPECTROSCOPY; SYSTEM AB A major problem in the development of high field (>100 MHz) large volume (>6000 cm(3)) MR coils is the interaction of the coil with the subject as well as the radiation loss to the environment. To reduce subject perturbation of the coil resonance modes, a volume coil that uses an array of freely rotating resonant elements radially mounted between two concentric cylinders was designed for operation at 170 MHz. Substantial electromagnetic energy is stored in the resonant elements outside the sample region without compromising the efficiency of the overall coil. This stored energy reduces the effect of the subject on the circuit and maintains a high Q, facilitating the tuning and matching of the coil. The unloaded Q of the coil is 680; when loaded with a head, it was 129. The ratio of 5.3 of the unloaded to loaded Q supports the notion that the efficiency of the coil was maintained in comparison with previous designs. The power requirement and signal-to-noise performance are significantly improved. The coil is tuned by a mechanism that imparts the same degree of rotation on all of the elements simultaneously, varying their degree of mutual coupling and preserving the overall coil symmetry. A thin radiofrequency shield is an integral part of the coil to reduce the radiation effect, which is a significant loss mechanism at high fields. MR images were collected at 4T using this coil design with high sensitivity and B-1 homogeneity. RP WEN, H (reprint author), NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [Z01 HL004606-11] NR 17 TC 48 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD OCT PY 1994 VL 32 IS 4 BP 492 EP 498 DI 10.1002/mrm.1910320411 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PJ323 UT WOS:A1994PJ32300010 PM 7997115 ER PT J AU TURNER, R JEZZARD, P AF TURNER, R JEZZARD, P TI Magnetic resonance functional imaging of the brain at 4 T SO MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 1st Nottingham Symposium on Magnetic Resonance Imaging CY 1994 CL NOTTINGHAM, ENGLAND DE BRAIN MAPPING; FUNCTIONAL MRI; BOLD CONTRAST; 4 TESLA; EPI ID PRIMARY VISUAL-CORTEX; SENSORY STIMULATION; SIGNAL CHANGES; GRADIENT-ECHO; BLOOD; RESOLUTION; ACTIVATION; CONTRAST; TESLA; TIME AB Blood Oxygenation Level Dependent (BOLD) contrast imaging of human brain function using echo-planar imaging at 4 T gives good freedom from motion artifact, high signal-to-noise ratio/unit time, and adequate spatial resolution. Studies were made of brain activation associated with perceptual and cognitive tasks of several minutes duration. Several cortical areas show task-dependent activity consistent across subjects, in images with a spatial resolution of 2.5 mm x 2.5 mm x 5 mm and a temporal resolution of up to 1 s. Multislice data were obtained at a rate of up to five slices per second. At 4 T, fractional changes of magnetic resonance (MR) image intensity up to 25% were observed. Novel cross-correlation methods, including the effect of the temporal point-spread function associated with the relatively slow hemodynamic response of the brain, allow activation maps of the brain to be generated with statistically meaningful thresholds. With appropriate data analysis, it is clear that oxygenation changes in large draining veins distant from active neural tissue do not dominate the changes observed, especially when brain tasks activating only a limited Volume of gray matter are chosen. This is consistent with downstream dilution of brood oxygenation changes and direct optical observations of functional brain activity in animals. C1 INST NEUROL,LONDON WC1N 3BG,ENGLAND. NIH,BETHESDA,MD 20892. OI Jezzard, Peter/0000-0001-7912-2251 NR 43 TC 6 Z9 6 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 1352-8661 J9 MAGN RESON MATER PHY JI Magn. Reson. Mat. Phys. Biol. Med. PD OCT PY 1994 VL 2 IS 3 BP 147 EP 156 DI 10.1007/BF01705234 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QB906 UT WOS:A1994QB90600003 ER PT J AU ASHAR, HR BENSON, KF JENKINS, NA GILBERT, DJ COPELAND, NG CHADA, KK AF ASHAR, HR BENSON, KF JENKINS, NA GILBERT, DJ COPELAND, NG CHADA, KK TI IFG, GLI, MDM1, MDM2, AND MDM3 - CANDIDATE GENES FOR THE MOUSE PG LOCUS SO MAMMALIAN GENOME LA English DT Article ID MOLECULAR ANALYSIS; LINKAGE MAP; CELL-LINE; AMPLIFICATION; CHROMOSOME-10; ORGANIZATION; ONCOGENE; SARCOMAS; DNA AB Various genes that mapped to the distal end of Chromosome (Chr) 10 were considered as possible candidates for the mouse pygmy (pg) locus. Probes derived from Ifg, Gli, Mdm1, Mdm2, and Mdm3 (Mdm2 and Mdm3 are genes that are coamplified with Mdm1 on the same double minute chromosomes in 3T3DM cells) were used for Southern analysis of DNA from wild-type mice and various pg mutants. In addition, the chromosomal locations of Ifg, Gli, Mdm1, Mdm2, and Mdm3 were determined by interspecific backcross analysis with progeny derived from matings of [(C57BL/6J X Mus spretus)F-1 X C57BL/6J] mice. The mapping data indicate that the Mdm loci are linked to each other and to Ifg, pg, and Gli in the distal region of mouse Chr 10. Both the mapping data and the Southern analysis confirm that Mdm1, Mdm2, Mdm3, Ifg, and Gli are distinct from pg. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT BIOCHEM,PISCATAWAY,NJ 08854. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM38731] NR 21 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1994 VL 5 IS 10 BP 608 EP 611 DI 10.1007/BF00411454 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PL429 UT WOS:A1994PL42900002 PM 7849395 ER PT J AU LEE, K KEITZ, B TAIRA, M CHAPMAN, VM AF LEE, K KEITZ, B TAIRA, M CHAPMAN, VM TI LINKAGE OF PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE-1 AND SYNTHETASE-2, PRPS1 AND PRPS2, ON THE MOUSE X-CHROMOSOME SO MAMMALIAN GENOME LA English DT Article ID COMPLETE CDNA SEQUENCE; I PRS-I; PYROPHOSPHATE SYNTHETASE; SUBUNIT-II; PROTEOLIPID PROTEIN; NUCLEOTIDE; CLONING; GENES; LOCALIZATION AB The X Chromosome (Chr) genes for phosphoribosylpyrophosphate synthetases 1 and 2, Prps1 and Prps2, were mapped on the mouse X Chr with interspecific backcrosses between C57BL/6 (B6) and M. spretus (S). Southern analysis showed that Prps1 mapped between Plp and DXWas31, a mouse X Chr region that is homologous to Xq21-24 on the human X Chr while Prps2 mapped between DXWas31 and Amg, a region that is homologous to the map position of PRPS2 on Xp22 of the human X Chr. Additionally, other restriction fragments highlighted by PRS II showed autosomal segregation. In situ hybridization and FISH analysis of metaphase chromosome spreads prepared from lymphocytes of B6 or S male mice confirmed that there were in fact two different locations on the X Chr, X F1-2 and X F2-3 for Prps1 and 2 respectively, as well as two autosomal sites for Prps-like genes. C1 ROSWELL PK CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14263. NIH,GENET MOLEC LAB,BETHESDA,MD 20892. NR 21 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1994 VL 5 IS 10 BP 612 EP 615 DI 10.1007/BF00411455 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PL429 UT WOS:A1994PL42900003 PM 7849396 ER PT J AU FERRARIS, JD FAUCHALD, K KENSLEY, B AF FERRARIS, JD FAUCHALD, K KENSLEY, B TI PHYSIOLOGICAL-RESPONSES TO FLUCTUATION IN TEMPERATURE OR SALINITY IN INVERTEBRATES - ADAPTATIONS OF ALPHEUS-VIRIDARI (DECAPODA, CRUSTACEA), TEREBELLIDES-PARVA (POLYCHAETA) AND GOLFINIGIA-CYLINDRATA (SIPUNCULIDA) TO THE MANGROVE HABITAT SO MARINE BIOLOGY LA English DT Article ID VOLUME REGULATION; DECEREBRATION; NEMERTINA; K+ AB The snapping shrimp Alpheus viridari (Armstrong, 1949), the polychaete Terebellides parva Solis-Weiss, Fauchald and Blankensteyn 1990, and the sipunculan Golfingia cylindrata (Keferstein, 1865) are commonly found in the same mangrove habitat, where they experience frequent, acute fluctuations in temperature and salinity. Ecological studies indicate a temporal variation, including occasional absence, in the distribution of both G. cylindrata and T. parva; this led us to examine the physiological adaptations of the three species (collected at Western Bay, Twin Cays, Belize in 1985, 1986 and 1988). Each was subjected to acute, repeated exposure to either control (35 parts per thousand S) and decreased (25 parts per thousand S) salinity or to control and increased (45 parts per thousand S) salinity. Ability to regulate water and ion content (g H2O or mu mol g(-1) solute free dry wt) was examined. A. viridari behaved as a hyperosmotic conformer at decreased salinity but as an osmoconformer at increased salinity. Regardless of direction of salinity change, A. viridari regulated water content through change in Na+, K+, and Cl- contents. In contrast, G. cylindrata behaved as an osmoconformer and did not demonstrate ability to regulate water content. T. parva behaved as an osmoconformer, showed incomplete regulation of water content via change in Na+, K+, and Cl- contents but had limited survival following exposure to 45 parts per thousand S. Each species was also exposed to change in temperature. Species were subjected to acute, repeated exposure either to control (28 degrees C) and decreased (21 degrees C) temperature or to control and increased (35 degrees C) temperature. A. viridari regulated water and ion content under both experimental conditions. In contrast, T. parva did not regulate water and ion content under either experimental temperature. G. cylindrata did not regulate water and ion content during exposure to decreased temperature and did not survive exposure to increased temperature. For A. viridari, weight specific oxygen uptake rates (mg O-2 g(-1) ash-free dry wt) were determined. Exposure to decreased salinity or to increased temperature resulted in a small sustained elevation in O-2 uptake. It is concluded that, unlike A. viridari, T. parva and G. cylindrata are only marginally adapted to withstand the salinity and temperature stresses, respectively, of the mangrove habitat. The inability of T. parva and G. cylindrata to fully adapt to extremes in the mangrove habitat could well explain the temporal variation seen in the distribution of these two species. C1 NATL MUSEUM NAT HIST, SMITHSONIAN INST, WASHINGTON, DC 20560 USA. RP FERRARIS, JD (reprint author), NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. NR 29 TC 15 Z9 16 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0025-3162 J9 MAR BIOL JI Mar. Biol. PD OCT PY 1994 VL 120 IS 3 BP 397 EP 406 DI 10.1007/BF00680213 PG 10 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA PP945 UT WOS:A1994PP94500008 ER PT J AU MEDIAVILLA, JD JAFFE, ES AF MEDIAVILLA, JD JAFFE, ES TI DIARRHEA, ADENOPATHIES AND PULMONARY-LESIONS IN A 42-YEAR-OLD MALE WITH COMMON VARIABLE IMMUNODEFICIENCY SO MEDICINA CLINICA LA Spanish DT Article ID HYPOGAMMAGLOBULINEMIA; DEFICIENCY; CANCER C1 NCI, PATHOL LAB, HEMATOPATHOL SECT, BETHESDA, MD 20892 USA. RP MEDIAVILLA, JD (reprint author), HOSP CLIN SAN CARLOS, SERV HEMATOL, MADRID, SPAIN. NR 24 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0025-7753 EI 1578-8989 J9 MED CLIN-BARCELONA JI Med. Clin. PD OCT 1 PY 1994 VL 103 IS 10 BP 388 EP 395 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PL874 UT WOS:A1994PL87400010 ER PT J AU CARRERA, L CHIARAMONTE, M KUHN, R MULLER, W SACKS, D SHER, A GAZZINELLI, RT AF CARRERA, L CHIARAMONTE, M KUHN, R MULLER, W SACKS, D SHER, A GAZZINELLI, RT TI LEISHMANIA-MAJOR AND TOXOPLASMA-GONDII HAVE OPPOSITE EFFECTS ON CYTOKINE SYNTHESIS BY MACROPHAGES SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article C1 UNIV COLOGNE,INST GENET,W-5000 COLOGNE,GERMANY. RP CARRERA, L (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20852, USA. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 0 TC 1 Z9 1 U1 0 U2 1 PU MEM INST OSWALDO CRUZ PI RIO DE JANEIRO PA SECRETARY CAIXA POSTAL 926, 20001 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD OCT-DEC PY 1994 VL 89 IS 4 BP 649 EP 650 PG 2 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA QH161 UT WOS:A1994QH16100024 PM 8524067 ER PT J AU VANBEMMEL, JH LINDBERG, DAB BALL, MJ AMAUD, P MACFARLANE, P RUBEL, P ZYWIETZ, C AF VANBEMMEL, JH LINDBERG, DAB BALL, MJ AMAUD, P MACFARLANE, P RUBEL, P ZYWIETZ, C TI IN HONOR OF THE MEMORY OF WILLEMS,JOS SO METHODS OF INFORMATION IN MEDICINE LA English DT Item About an Individual C1 NATL LIB MED,BETHESDA,MD 20894. RP VANBEMMEL, JH (reprint author), ERASMUS UNIV ROTTERDAM,DEPT MED INFORMAT,POB 1738,3000 DR ROTTERDAM,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD OCT PY 1994 VL 33 IS 4 BP R5 EP R5 PG 1 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA PN899 UT WOS:A1994PN89900001 ER PT J AU KANNO, T BROWN, K FRANZOSO, G SIEBENLIST, U AF KANNO, T BROWN, K FRANZOSO, G SIEBENLIST, U TI KINETIC-ANALYSIS OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX-MEDIATED ACTIVATION OF NF-KAPPA-B SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING PROTEINS; TUMOR-NECROSIS-FACTOR; DNA-BINDING; HTLV-I; C-REL; TRANSCRIPTIONAL ACTIVATOR; GENE-PRODUCT; ONCOPROTEIN BCL-3; NUCLEAR TRANSLOCATION; 21-BASE-PAIR REPEATS AB The human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of cellular genes, at least in part, by activating the endogenous NF-kappa B transcription factors. Induced expression of cellular genes is thought to be important for transformation of T cells to continued growth, a prelude to the establishment of adult T-cell leukemia. However, neither underlying mechanisms nor kinetics of the Tax-mediated activation of NF-kappa B are understood, We have analyzed a permanently transfected Jurkat T-cell line in which the expression of Tax is entirely dependent on addition of heavy metals. The initial NF-kappa B binding activity seen after induction of Tax is due almost exclusively to p50/p65 heterodimers. At later times, NF-kappa B complexes containing c-Rel and/or p52 accumulate. The early activation of p50/p65 complexes is a posttranslational event, since neither mRNA nor protein levels of NF-kappa B subunits had increased at that time. We demonstrate for the first time a Tax-induced proteolytic degradation of the NF-kappa B inhibitor, I kappa B-alpha, which may trigger the initial nuclear translocation of NF-kappa B. As nuclear NF-kappa B rapidly and potently stimulates resynthesis of I kappa B-alpha, the steady-state level of I kappa B-alpha does not significantly change, Thus, the dramatic Tax-induced increase in the I kappa B-alpha turnover may continually weaken inhibition and activate NF-kappa B. Additional, distinct actions of Tax may contribute further to the high levels of NP-kappa B activity seen, C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 75 TC 86 Z9 86 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6443 EP 6451 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100004 PM 7935369 ER PT J AU SHARON, G BURKETT, TJ GARFINKEL, DJ AF SHARON, G BURKETT, TJ GARFINKEL, DJ TI EFFICIENT HOMOLOGOUS RECOMBINATION OF TY1 ELEMENT CDNA WHEN INTEGRATION IS BLOCKED SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; POLYMERASE CHAIN-REACTION; SACCHAROMYCES-CEREVISIAE; YEAST RETROTRANSPOSON; DIRECTED MUTAGENESIS; OVERLAP EXTENSION; GENE-EXPRESSION; SPT3 GENE; TRANSPOSITION; DNA AB Integration of the yeast retrotransposon Ty1 into the genome requires the self-encoded integrase (IN) protein and specific terminal nucleotides present on full-length Ty1 cDNA. Ty1 mutants with defects in IN, the conserved termini of Ty1 cDNA, or priming plus-strand DNA synthesis, however, were still able to efficiently insert into the genome when the elements were expressed from the GAL1 promoter present on a multicopy plasmid. As with normal transposition, formation of the exceptional insertions required an RNA intermediate, Ty1 reverse transcriptase, and Ty1 protease. In contrast to Ty1 transposition, at least 70% of the chromosomal insertions consisted of complex multimeric Ty1 elements. Ty1 cDNA was transferred to the inducing plasmid as well as to the genome, acid transfer required the recombination and repair gene RAD52. Furthermore, multimeric insertions occurred without altering the levels of total Ty1 RNA, virus-like particle-associated RNA or cDNA, Ty1 capsid proteins, or IN. These results suggest that Ty1 cDNA is utilized much more efficiently for homologous recombination when IN-mediated integration is blocked. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, EUKARYOT GENE EXPRESS LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101] NR 59 TC 73 Z9 73 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6540 EP 6551 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100014 PM 7523854 ER PT J AU RABINDRAN, SK WISNIEWSKI, J LI, LG LI, GC WU, C AF RABINDRAN, SK WISNIEWSKI, J LI, LG LI, GC WU, C TI INTERACTION BETWEEN HEAT-SHOCK FACTOR AND HSP70 IS INSUFFICIENT TO SUPPRESS INDUCTION OF DNA-BINDING ACTIVITY IN-VIVO SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION DOMAIN; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; FACTOR CONTAINS; HELA-CELLS; YEAST; PROTEIN; GENE; STRESS; OLIGOMERIZATION AB The intracellular level of free heat shock proteins, in particular the 70-kDa stress protein family, has been suggested to be the basis of an autoregulatory mechanism by which the cell measures the level of thermal stress and regulates the synthesis of heat shock proteins. It has been proposed that the DNA-binding and oligomeric state of the heat shock transcription factor (HSF) is a principal step in the induction pathway that is responsive to the level of 70-kDa stress protein. To test this hypothesis, we investigated the association between HSF and 70-kDa stress protein by means of a coimmunoprecipitation assay. We found that 70-kDa stress proteins associate to similar extents with both latent and active forms of HSF, although unlike other 70-kDa stress protein substrates, the association with HSF was not significantly disrupted in the presence of ATP. Gel mobility shift assays indicated that active HSF trimers purified from a bacterial expression system could not be substantially deactivated in vitro with purified 70-kDa stress protein and ATP. In addition, elevated concentrations of hsp70 alone could not significantly inhibit induction of the DNA-binding activity of endogenous HSF in cultured rat cells, and the induction was also not inhibited in cultured rat cells or Drosophila cells containing elevated levels of all members of the heat shock protein family. However, the deactivation of HSF to the non-DNA-binding state after prolonged heat stress or during recovery could be accelerated by increased levels of heat shock proteins. Hence, the level of heat shock proteins may affect the rate of disassembly of HSF trimers, but another mechanism, as yet undefined, appears to control the onset of the oligomeric transitions. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NR 59 TC 120 Z9 121 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6552 EP 6560 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100015 PM 7935376 ER PT J AU HAFNER, S ADLER, HS MISCHAK, H JANOSCH, P HEIDECKER, G WOLFMAN, A PIPPIG, S LOHSE, M UEFFING, M KOLCH, W AF HAFNER, S ADLER, HS MISCHAK, H JANOSCH, P HEIDECKER, G WOLFMAN, A PIPPIG, S LOHSE, M UEFFING, M KOLCH, W TI MECHANISM OF INHIBITION OF RAF-1 BY PROTEIN-KINASE-A SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SERINE-THREONINE KINASE; MAP KINASE; SIGNAL-TRANSDUCTION; BIOLOGICAL-ACTIVITY; TYROSINE KINASE; V-RAF; ACTIVATION; GROWTH; CELLS; PHOSPHORYLATION AB The cytoplasmic Raf-1 kinase is essential for mitogenic signalling by growth factors, which couple to tyrosine kinases, and by tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate, which activate protein kinase C (PKC). Signalling by the Raf-1 kinase can be blocked by activation of the cyclic AMP (cAMP)-dependent protein kinase A (PKA). The molecular mechanism of this inhibition is not precisely known but has been suggested to involve attenuation of Raf-1 binding to Ras. Using purified proteins, we show that in addition to weakening the interaction of Raf-1 with Ras, PKA can inhibit Raf-1 function directly via phosphorylation of the Raf-1 kinase domain. Phosphorylation by PKA interferes with the activation of Raf-1 by either PKC alpha or the tyrosine kinase Lck and even can downregulate the kinase activity of Raf-1 previously activated by PKC alpha or amino-terminal truncation. This type of inhibition can be dissociated from the ability of Raf-1 to associate with Ras, since (i) the isolated Raf-1 kinase domain, which lacks the Ras binding domain, is still susceptible to inhibition by PKA, (ii) phosphorylation of Raf-1 by PKC alpha alleviates the PKA-induced reduction of Ras binding but does not prevent the downregulation of Raf-1 kinase activity by PKA and (iii) cAMP agonists antagonize transformation by v-Raf, which is Ras independent. C1 HAMATOLOGIKUM,INST KLIN MOLEK BIOL & TUMOR GENET GSF,D-81377 MUNICH,GERMANY. UNIV MUNICH,MOLEC BIOL LAB,D-82152 MARTINSRIED,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21072. CLEVELAND CLIN FDN,DEPT CELL BIOL,CLEVELAND,OH 44195. RI Mischak, Harald/E-8685-2011; Lohse, Martin/A-7160-2012; OI Lohse, Martin/0000-0002-0599-3510; Kolch, Walter/0000-0001-5777-5016 NR 48 TC 273 Z9 277 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6696 EP 6703 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100030 PM 7935389 ER PT J AU LI, WQ YU, JC MICHIELI, P BEELER, JF ELLMORE, N HEIDARAN, MA PIERCE, JH AF LI, WQ YU, JC MICHIELI, P BEELER, JF ELLMORE, N HEIDARAN, MA PIERCE, JH TI STIMULATION OF THE PLATELET-DERIVED GROWTH-FACTOR-BETA RECEPTOR SIGNALING PATHWAY ACTIVATES PROTEIN-KINASE C-DELTA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEMATOPOIETIC-CELLS; DOWN-REGULATION; PHORBOL ESTER; DIFFERENTIATION; PDGF; TRANSDUCTION; EXPRESSION; ALPHA; PHOSPHORYLATION; DEGRADATION AB The murine myeloid progenitor cell line 32D was recently shown to undergo monocytic differentiation when protein kinase C-delta (PKC-delta) was overexpressed and activated by 12-O-tetradecanoylphqrbol-13-acetate (TPA) (H. Mischak, J. Il. Pierce, J. Goodnight, M; G. Kazanietz, P. M. Blumberg, and J. F. Mushinski, J. Biol. Chem. 268:20110-20115, 1993). Tyrosine phosphorylation of PKC-delta occurred when PKC-delta-transfected 32D cells were stimulated by TPA (W. Li, H. Mischak, J.-C. Yu, L.-M. Wang, J. F; Mushinski, M. A. Heidaran, and J. H. Pierce, J. Biol. Chem. 269:2349-2352, 1994). In order to elucidate the role played by PKC-delta in response to activation of a receptor tyrosine kinase, we transfected platelet-derived growth factor beta receptor (PDGF-beta R) alone (32D/PDGF-beta R) or together with PKC-delta (32D/PDGF-beta R/PKC-delta) into 32D cells. NIH 3T3 cells which endogenously express both PDGF-alpha R and PDGF-beta R were also transfected with PKC-delta (NIH 3T3/PKC-delta). Like TPA treatment, PDGF-BB stimulation caused striking phosphorylation of PKC-delta in vivo and translocation of some PKC-delta from the cytosol fraction to the membrane fraction in both cell systems. Some of the phosphorylation induced by PDGF-BB treatment was found to be on a tyrosine residue(s). Tyrosine-phosphorylated PKC-delta was observed only for the membrane fraction after stimulation with PDGF-BB or TPA. The enzymatic activity of PKC-delta in the membrane fraction also increased after stimulation with TPA or PDGF, providing a positive correlation between PKC-delta tyrosine phosphorylation and its activation. Overnight treatment Of 32D/PDGF-beta R/PKC-delta cells with PDGF-BB induced monocytic differentiation as judged by an increase in expression of cell surface microphage differentiation markers. PDGF-BB had much weaker effects on 32D/PDGF-beta R cell differentiation, suggesting that increased PKC-delta expression enhanced monocytic differentiation. These results indicate that PKC-delta is a downstream molecule in the PDGFR signaling pathway and may play a pivotal role in PDGF-beta R-mediated cell differentiation. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Michieli, Paolo/A-2588-2011 NR 36 TC 106 Z9 107 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6727 EP 6735 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100033 PM 7935392 ER PT J AU KHOSRAVIFAR, R CHRZANOWSKAWODNICKA, M SOLSKI, PA EVA, A BURRIDGE, K DER, CJ AF KHOSRAVIFAR, R CHRZANOWSKAWODNICKA, M SOLSKI, PA EVA, A BURRIDGE, K DER, CJ TI DBL AND VAV MEDIATE TRANSFORMATION VIA MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAYS THAT ARE DISTINCT FROM THOSE ACTIVATED BY ONCOGENIC RAS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTP-BINDING PROTEINS; GUANINE-NUCLEOTIDE EXCHANGE; TYPE-1 NEUROFIBROMATOSIS; BCR GENE; PRODUCT; DOMAIN; CELLS; SIGNAL; PROTOONCOGENE; GROWTH AB Vav and Dbl are members of a novel class of oncogene proteins that share significant sequence identity in a similar to 250-amino-acid domain, designated the Dbl homology domain. Although Dbl functions as a guanine nucleotide exchange factor (GEF) and activator of Rho family proteins, recent evidence has demonstrated that Vav functions as a GEF for Ras proteins. Thus, transformation by Vav and Dbl may be a consequence of constitutive activation of Ras and Rho proteins, respectively. To address this possibility, we have compared the transforming activities of Vav and Dbl with that of the Ras GEF, GRF/CDC25. As expected, GRF-transformed cells exhibited the same reduction in actin stress fibers and focal adhesions as Res-transformed cells. In contrast, Vav- and Dbl-transformed cells showed the same well-developed stress fibers and focal adhesions observed in normal or RhoA(63L)-transformed NIH 3T3 cells. Furthermore, neither Vav- or Dbl-transformed cells exhibited the elevated levels of Ras-GTP (60%) observed with GRF-transformed cells. Finally, GRF, but not Vav or Dbl, induced transcriptional activation from Ras-responsive DNA elements (ets/AP-1, fos promoter, and kappa B). However, like Ras- and GRF-transformed cells, both Vav- and Dbl-transformed cells exhibited constitutively activated mitogen-activated protein kinases (MAPKs) (primarily p42(MAPK)/ERK2). Since kinase-deficient forms of p42(MAPK)/ERK2 and p44(MAPK)/ERK1 inhibited Dbl transformation, MAPK activation may be an important component of its transforming activity. Taken together, our observations indicate that Vav and Dbl transformation is not a consequence of Ras activation and instead may involve the constitutive activation of MAPKs. C1 UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELLULAR BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Khosravi-Far, Roya/C-3789-2008; Eva, Alessandra/J-8268-2016; OI Eva, Alessandra/0000-0003-2949-078X; Chrzanowska-Wodnicka, Magdalena/0000-0003-4182-2126 FU NCI NIH HHS [CA63071, CA42978, CA52072] NR 60 TC 137 Z9 137 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6848 EP 6857 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100045 PM 7935402 ER PT J AU MEIER, JL LUO, X SAWADOGO, M STRAUS, SE AF MEIER, JL LUO, X SAWADOGO, M STRAUS, SE TI THE CELLULAR TRANSCRIPTION FACTOR USF COOPERATES WITH VARICELLA-ZOSTER VIRUS IMMEDIATE-EARLY PROTEIN-62 TO SYMMETRICALLY ACTIVATE A BIDIRECTIONAL VIRAL PROMOTER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX-LOOP-HELIX; ADENOVIRUS MAJOR LATE; DNA-BINDING PROPERTIES; OPEN READING FRAME-62; RNA POLYMERASE-II; PSEUDORABIES VIRUS; REGULATORY PROTEIN; ZIPPER PROTEIN; MULTIPLE FORMS; GENE AB The mechanisms governing the function of cellular USF and herpesvirus immediate-early transcription factors are subjects of considerable interest. In this regard, we identified a novel form of coordinate gene regulation involving a cooperative interplay between cellular USF and the varicella-zoster virus immediate-early protein 62 (IE 62). A single USF-binding site defines the potential level of IE 62-dependent activation of a bidirectional viral early promoter of the DNA polymerase and major DNA-binding protein genes. We also report a dominant negative USF-2 mutant lacking the DNA-binding domain that permits the delineation of the biological role of both USF-1 and USF-2 in this activation process. The symmetrical stimulation of the bidirectional viral promoter by LE 62 is achieved at concentrations of USF-1 (43 kDa) or USF-2 (44 kDa) already existing in cells. Our observations support the notion that cellular USP can intervene in and possibly target promoters for activation by a herpesvirus immediate-early protein. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC GENET,HOUSTON,TX 77030. FU NIGMS NIH HHS [GM38212] NR 78 TC 101 Z9 102 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6896 EP 6906 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100050 PM 7935407 ER PT J AU DETLOFF, PJ LEWIS, J JOHN, SWM SHEHEE, WR LANGENBACH, R MAEDA, N SMITHIES, O AF DETLOFF, PJ LEWIS, J JOHN, SWM SHEHEE, WR LANGENBACH, R MAEDA, N SMITHIES, O TI DELETION AND REPLACEMENT OF THE MOUSE ADULT BETA-GLOBIN GENES BY A PLUG AND SOCKET REPEATED TARGETING STRATEGY SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; HOMOLOGOUS RECOMBINATION; TRANSGENIC MICE; DNA-SEQUENCES; TRANSCRIPTION; MUTAGENESIS; THALASSEMIA; HEMOGLOBIN; DISRUPTION; EXPRESSION AB We describe a two-step strategy to alter any mouse locus repeatedly and efficiently by direct positive selection. Using conventional targeting for the first step, a functional neo gene and a nonfunctional HPRT minigene (the ''socket') are introduced into the genome of HPRT(-) embryonic stem (ES) cells dose to the chosen locus, in this case the beta-globin locus. For the second step, a targeting construct (the ''plug'') that recombines homologously with the integrated socket and supplies the remaining portion of the HPRT minigene is used; this homologous recombination generates a functional HPRT gene and makes the ES cells hypoxanthine-aminopterin-thymidine resistant. At the same time, the plug provides DNA sequences that recombine homologously with sequences in the target locus and modifies them in the desired manner; the plug is designed so that correctly targeted cells also lose the neo gene and become G418 sensitive. We have used two different plugs to make alterations in the mouse beta-globin locus starting with the same socket-containing ES cell line. One plug deleted 20 kb of DNA containing the two adult beta-globin genes. The other replaced the same region with the human beta-globin gene containing the mutation responsible for sickle cell anemia. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. GLAXO INC,RES INST,DEPT BIOCHEM,RES TRIANGLE PK,NC 27709. GLAXO INC,RES INST,DEPT CELL BIOL,RES TRIANGLE PK,NC 27709. NIEHS,EXPT CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NHLBI NIH HHS [HL37001]; NIGMS NIH HHS [GM20069] NR 26 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6936 EP 6943 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100054 PM 7935410 ER PT J AU MEDIN, JA MINUCCI, S DRIGGERS, PH LEE, IJ OZATO, K AF MEDIN, JA MINUCCI, S DRIGGERS, PH LEE, IJ OZATO, K TI QUANTITATIVE INCREASES IN DNA-BINDING AFFINITY AND POSITIONAL EFFECTS DETERMINE 9-CIS RETINOIC ACID-INDUCED ACTIVATION OF THE RETINOID-X RECEPTOR-BETA HOMODIMER SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE RETINOID X RECEPTOR; 9-CIS-RETINOIC ACID; HOMODIMER; TRANSCRIPTIONAL REGULATION ID THYROID-HORMONE RECEPTOR; RESPONSE ELEMENTS; DIRECT REPEAT; RXR-ALPHA; II GENE; HETERODIMERS; TRANSCRIPTION; PATHWAYS; CELLS; RAR AB Retinoid X receptors (RXRs) exert transcriptional activities through heterodimerization with members of the nuclear hormone receptor superfamily. RXRs also act as homodimers and stimulate transcription from an RXR responsive element (RXRE) when bound to 9-cis-retinoic acid (9cRA). Here direct effects of 9cRA have been examined on biochemical and mechanistic parameters of RXR beta. It is shown that 9cRA significantly increases RXR beta homodimer binding affinity to an RXRE (K-d without ligand = 18 nM, K-d with ligand = 6 nM), while decreasing significantly the affinity of RXR beta/thyroid hormone receptor (T3R alpha) heterodimer binding to the same element. Effects on other response elements are also examined. The RXR beta homodimer was found to contact both halves of the RXRE direct repeat, irrespective of the effect of added ligand, while the RXR beta/T3R alpha heterodimer contacted the element only through a specific half-site. Binding of the homodimer to the element functionally activates RXR beta, since RXR beta enhanced transcription in vitro from a specific template in a ligand-dependent fashion. In agreement, transfection of RXR beta alone (but not RXR beta/T3R alpha) led to ligand-dependent activation of a reporter containing the RXRE. Taken together, 9cRA facilitates functional activation of the RXR beta homodimer in an element-dependent manner. C1 NICHHD,LMGR,BETHESDA,MD 20892. RI Minucci, Saverio/J-9669-2012 NR 40 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT PY 1994 VL 105 IS 1 BP 27 EP 35 DI 10.1016/0303-7207(94)90032-9 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA PJ175 UT WOS:A1994PJ17500004 PM 7821715 ER PT J AU LINDER, B HARRIS, S EISEN, A NISSLEY, P AF LINDER, B HARRIS, S EISEN, A NISSLEY, P TI EVIDENCE AGAINST ROLES FOR PERTUSSIS-TOXIN-SENSITIVE C-PROTEINS OR DIACYLGLYCEROL GENERATION IN INSULIN-LIKE GROWTH-FACTOR-I STIMULATED DNA-SYNTHESIS IN MG-63 OSTEOSARCOMA CELLS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE PERTUSSIS TOXIN; G PROTEINS; INSULIN-LIKE GROWTH FACTOR-I; IGF-I RECEPTOR; DIACYLGLYCEROL; MG-63 HUMAN OSTEOSARCOMA CELLS ID I IGF-I; SIGNAL TRANSDUCTION; KINASE-C; THYROID-CELLS; 3T3 CELLS; RECEPTOR; 1,2-DIACYLGLYCEROL; FIBROBLASTS; ACTIVATION; PATHWAYS AB A pertussis toxin-sensitive G protein has been reported to play a role in the mitogenic response to insulin-like growth factor-I (IGF-I) in mouse fibroblasts, and diacyglycerol generation has been shown to accompany growth stimulation by IGF-I of several cell lines. We have examined the roles of pertussis toxin sensitive G proteins and diacylglycerol generation in signaling by the insulin-like growth factor-I receptor in a cell line that is very responsive to IGF-I, the human osteosarcoma cell line, MG-63. Pertussis toxin failed to inhibit IGF-I induced [H-3]-thymidine incorporation into DNA. Furthermore, the stable analog GTP gamma S had no effect on the binding of I-125-labelled IGF-I to MG-63 membrane preparations. Following addition of IGF-I to growth-arrested MG-63 cells there was no increase in diacylglycerol levels over 30 min. We conclude that the activated IGF-I receptor does not use pertussis toxin sensitive G proteins or diacylglycerol generation in a pathway leading to DNA synthesis in MG-63 cells. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 28 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT PY 1994 VL 105 IS 1 BP 111 EP 118 DI 10.1016/0303-7207(94)90042-6 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA PJ175 UT WOS:A1994PJ17500014 PM 7821713 ER PT J AU LIU, X YAO, DL BONDY, CA BRENNER, M HUDSON, LD ZHOU, J WEBSTER, HD AF LIU, X YAO, DL BONDY, CA BRENNER, M HUDSON, LD ZHOU, J WEBSTER, HD TI ASTROCYTES EXPRESS INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND ITS BINDING-PROTEIN, IGFBP-2, DURING DEMYELINATION INDUCED BY EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; RECEPTOR GENE-EXPRESSION; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; HYPOXIC-ISCHEMIC INJURY; RAT-BRAIN; MESSENGER-RNA; SPINAL-CORD; OLIGODENDROCYTE DEVELOPMENT; CELLULAR-PATTERN; TRANSGENIC MICE AB To assess the distribution of insulin-like growtn-factor-related proteins during autoimmune CNS demyelination and remyelination, experimental autoimmune encephalomyelitis was produced by injecting Lewis rats with an emulsion containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia and incontinence were observed in some animals. From 8-40 days postinoculation (dpi), spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP mRNAs were increased in these lesions and transcripts encoding myelin basic protein (MBP) were greatly reduced. Large lesions with extensive demyelination were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi. MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin regenerating myelin sheaths were found morphologically. Astrocytes, identified by their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2 mRNA and peptide in normal controls; their levels were significantly higher 14 dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels were also elevated around lesions and in some normal-appearing areas of WM and GM 14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP-positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization and immunocytochemistry as well as by double immunostaining. Coexpression of IGF-I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time. This suggests that during lesion progression and recovery, astrocytic expression of IGF-I-related peptides may reduce immune-mediated myelin injury. We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons. (C) 1994 Academic Press, Inc. C1 NINCDS,STROKE BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RP LIU, X (reprint author), NINCDS,EXPTL NEUROPATHOL LAB,BLDG 36,RM 4A-29,BETHESDA,MD 20892, USA. NR 44 TC 76 Z9 76 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD OCT PY 1994 VL 5 IS 5 BP 418 EP 430 DI 10.1006/mcne.1994.1052 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PH399 UT WOS:A1994PH39900005 PM 7529631 ER PT J AU FUKUYAMA, R MURAKAWA, Y RAPOPORT, SI AF FUKUYAMA, R MURAKAWA, Y RAPOPORT, SI TI INDUCTION OF GENE-EXPRESSION OF AMYLOID PRECURSOR PROTEIN (APP) IN ACTIVATED HUMAN LYMPHOBLASTOID-CELLS AND LYMPHOCYTES SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE INFLAMMATION; CALCIUM; SIGNAL TRANSDUCTION; ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN; LYMPHOCYTES ID FAMILIAL ALZHEIMERS-DISEASE; DIFFERENTIAL EXPRESSION; ANTIGEN RECEPTOR; T-CELLS; BRAIN; MUTATION; LEUKOCYTES; SECRETION; INCREASES; ISOFORM AB To understand the possible role of amyloid precursor protein (APP) in human lymphocytes, and the regulation of APP gene expression in this cell type, we determined levels of cellular APP protein and of mRNA in human T-cell-derived Jurkat cells that were treated with lectin, phorbol ester, and calcium ionophore. We also related these levels to cell aggregation and adhesion. Cell-cell aggregation and cell-plastic adhesion were observed over a 24-h period after incubating cells for 2 h with phytohemagglutinin or phorbol myristate acetate. Cells treated with a calcium ionophore showed no aggregation or adhesion. Western blots indicated no obvious alteration in the level of cellular APP with different treatments. Northern blots showed a significant transient increase of APP mRNA after incubation with the calcium ionophore, whereas phorbol ester treatment showed a slight increase of APP mRNA. We analyzed the level of APP mRNA in human peripheral T cells which had been separated from peripheral lymphocytes. The level increased transiently by up to threefold after treatment with calcium ionophore plus phorbol esters. These data suggest that cell-cell aggregation and cell-matrix adhesion by human lymphocytes are not associated with an increased level of cellular APP protein or of mRNA. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP FUKUYAMA, R (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD OCT-DEC PY 1994 VL 23 IS 2-3 BP 93 EP 101 DI 10.1007/BF02815403 PG 9 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PY906 UT WOS:A1994PY90600002 PM 7702710 ER PT J AU RAJASEKARAN, AK HUMPHREY, JS WAGNER, M MIESENBOCK, G LEBIVIC, A BONIFACINO, JS RODRIGUEZBOULAN, E AF RAJASEKARAN, AK HUMPHREY, JS WAGNER, M MIESENBOCK, G LEBIVIC, A BONIFACINO, JS RODRIGUEZBOULAN, E TI TGN38 RECYCLES BASOLATERALLY IN POLARIZED MADIN-DARBY CANINE KIDNEY-CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TRANS-GOLGI NETWORK; LYSOSOMAL ACID-PHOSPHATASE; INTEGRAL MEMBRANE-PROTEIN; BREFELDIN-A; MDCK CELLS; CYTOPLASMIC DOMAIN; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; CACO-2 CELLS; RECEPTOR AB Sorting of newly synthesized plasma membrane proteins to the apical or basolateral surface domains of polarized cells is currently thought to take place within the trans-Golgi network (TGN). To explore the relationship between protein localization to the TGN and sorting to the plasma membrane in polarized epithelial cells, we have expressed constructs encoding the TGN marker, TGN38, in Madin-Darby canine kidney (MDCK) cells. We report that TGN38 is predominantly localized to the TGN of these cells and recycles via the basolateral membrane. Analyses of the distribution of Tac-TGN38 chimeric proteins in MDCK cells suggest that the cytoplasmic domain of TGN38 has information leading to both TGN localization and cycling through the basolateral surface. Mutations of the cytoplasmic domain that disrupt TGN localization also lead to nonpolarized delivery of the chimeric proteins to both surface domains. These results demonstrate an apparent equivalence of basolateral and TGN localization determinants and support an evolutionary relationship between TGN and plasma membrane sorting processes. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. SLOAN KETTERING INST,CELLULAR BIOCHEM & BIOPHYS PROGRAM,NEW YORK,NY 10021. FAC SCI LUMINY,F-13288 MARSEILLE,FRANCE. RP RAJASEKARAN, AK (reprint author), CORNELL UNIV,COLL MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10021, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 FU NIGMS NIH HHS [GM-34107, R01 GM034107] NR 50 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 1994 VL 5 IS 10 BP 1093 EP 1103 PG 11 WC Cell Biology SC Cell Biology GA PP142 UT WOS:A1994PP14200003 PM 7865877 ER PT J AU IKEDA, J NAKAJIMA, T OSBORNE, OC MIES, G NOWAK, TS AF IKEDA, J NAKAJIMA, T OSBORNE, OC MIES, G NOWAK, TS TI COEXPRESSION OF C-FOS AND HSP70 MESSENGER-RNA IN GERBIL BRAIN AFTER ISCHEMIA - INDUCTION THRESHOLD, DISTRIBUTION AND TIME-COURSE EVALUATED BY IN-SITU HYBRIDIZATION SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ISCHEMIA; GERBIL; C-FOS; HSP70; HEAT SHOCK; STRESS PROTEIN; HIPPOCAMPUS ID HEAT-SHOCK PROTEIN; MESSENGER-RNA EXPRESSION; IMMEDIATE-EARLY GENES; RAT CEREBRAL-CORTEX; TRANSIENT GLOBAL-ISCHEMIA; CEREBELLAR GRANULE CELLS; STRESS PROTEIN; INSITU HYBRIDIZATION; FOREBRAIN ISCHEMIA; MAMMALIAN BRAIN AB Levels of mRNAs encoding the proto-oncogene, c-fos, and the 70 kDa stress protein, hsp70, were evaluated in gerbil brain following transient cerebral ischemia of varied duration by in situ and blot hybridization techniques. Blots of total hippocampal RNA obtained after 5 min ischemic insults confirmed a characteristic, transient time course of c-fos expression with a striking elevation within 1 h and a return to control levels by 3 h recirculation. Hsp70 hybridization was significant at 1 h and continued to increase until 3-6 h after the insult. Striking accumulation of c-fos mRNA was detected within 15 min recirculation in dentate granule cells, persisting through 1 h, and a weaker signal was evident in CA1 and CA3 pyramidal neurons of hippocampus, as well as in prepiriform/entorhinal cortex and neocortical regions, during the same interval. Hsp70 hybridization showed an identical distribution at 1 h recirculation. Ischemic insults of 1 min duration resulted in no detectable increase of either mRNA, while 2 min ischemia resulted in changes comparable to those seen after 5 min insults. This common threshold corresponds to the ischemic interval required for energy depletion and resultant failure of intracellular ion homeostasis. In contrast, expression of hsp70 mRNA was not observed under conditions of brief depolarization accompanying cortical or hippocampal spreading depression that were shown to induce c-fos. A delayed component of c-fos mRNA expression was not detected in this model, while persistent hsp70 hybridization, restricted to hippocampal CA1 neurons, was evident at 48 h after either 2 min or 5 min ischemic insults. The parallels in c-fos and hsp70 mRNA expression during early recirculation suggest that overlapping mechanisms triggered following postischemic depolarization contribute to their induction after transient ischemia. C1 NINCDS,NEUROPATHOL & NEUROANAT SCI LAB,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 95 TC 59 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1994 VL 26 IS 1-2 BP 249 EP 258 DI 10.1016/0169-328X(94)90097-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PL657 UT WOS:A1994PL65700031 ER PT J AU CLARK, M MASSENBURG, GS WEISS, SRB POST, RM AF CLARK, M MASSENBURG, GS WEISS, SRB POST, RM TI ANALYSIS OF THE HIPPOCAMPAL GABA(A) RECEPTOR SYSTEM IN KINDLED RATS BY AUTORADIOGRAPHIC AND IN-SITU HYBRIDIZATION TECHNIQUES - CONTINGENT TOLERANCE TO CARBAMAZEPINE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE GABA(A)-BENZODIAZEPINE RECEPTOR COMPLEX; MESSENGER-RNA; KINDLED SEIZURE; HIPPOCAMPUS; CARBAMAZEPINE; RECEPTOR AUTORADIOGRAPHY; CONTINGENT TOLERANCE; IN SITU HYBRIDIZATION ID GAMMA-AMINOBUTYRIC ACID; DORSAL RAPHE NEURONS; BENZODIAZEPINE RECEPTORS; BRAIN; MODEL; LOCALIZATION; SEIZURES; BINDING; EPILEPSY; SUBUNIT AB Tolerance to the anticonvulsant effects of carbamazepine (CBZ) in the amygdala kindling paradigm is a contingent process, since it only develops in rats treated with CBZ before the kindling stimulation and not in those animals treated after the stimulation. The present study was designed to investigate the GABA(A) receptor system in CBZ contingent tolerance. Receptor autoradiography utilizing various radioligands that bind to different components of the GABA(A) receptor system and in situ hybridization with oligonucleotides that recognize different subunits of the GABA(A) receptor were performed. Kindling increased binding to benzodiazepine, picrotoxin, and GABA recognition sites selectively in the dentate gyrus of the hippocampus. Kindling also increased levels of mRNA for the alpha(4), beta(1), and beta(3) subunits but did not change alpha(1), alpha(2), or gamma(2), subunit levels. Rats tolerant to CBZ showed decreased [H-3]muscimol binding, diazepam-insensitive [H-3]Ro 15-4513 binding, and decreased alpha(4) subunit mRNA content compared to non-tolerant rats, whereas [H-3]flunitrazepam binding, [S-35]TBPS binding, and the levels of beta(1), and beta(3) Subunit mRNAs remained elevated. The data suggest an indirect interaction of CBZ with the GABA(A) receptor system, since CBZ reportedly does not bind to this receptor system. RP CLARK, M (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 41 TC 47 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1994 VL 26 IS 1-2 BP 309 EP 319 DI 10.1016/0169-328X(94)90104-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA PL657 UT WOS:A1994PL65700038 PM 7854061 ER PT J AU JOHNSON, M DIMITROV, D VOJTA, PJ BARRETT, JC NODA, A PEREIRASMITH, OM SMITH, JR AF JOHNSON, M DIMITROV, D VOJTA, PJ BARRETT, JC NODA, A PEREIRASMITH, OM SMITH, JR TI EVIDENCE FOR A P53-INDEPENDENT PATHWAY FOR UP-REGULATION OF SDI1/CIP1/WAF1/P21 RNA IN HUMAN-CELLS SO MOLECULAR CARCINOGENESIS LA English DT Note DE SDI1; P53; GROWTH ARREST; DNA DAMAGE; GENE EXPRESSION ID HUMAN-DIPLOID FIBROBLASTS; DNA-DAMAGING AGENTS; GROWTH ARREST; SENESCENT; INHIBITOR; INDUCTION; MUTATIONS; PROTEINS; KINASES; GENE AB SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening cDNAs prepared from senescent, terminally nondividing human cells. Other groups then cloned this gene as a cyclin-dependent kinase (cdk)-interacting protein (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes transactivated by p53 (WAF1). p53 levels are low in senescent and quiescent contact-inhibited or serum-deprived normal human cells, which we have found express high levels of SDI1 mRNA. This indicates that alternate pathways for upregulation of message level of this gene may exist. We therefore proceeded with the study presented here, treating human cells with a variety of growth-arrest-inducing agents, including some that damaged DNA, and found that RNA levels of SDI1 were increased in all cases that resulted in growth inhibition. More important, with the exception of gamma-radiation, most of these agents were able to elevate SDI1 message levels in cells lacking wild-type p53. At least two distinct kinetic profiles for RNA induction were observed, one that implicated p53 transactivation and occurred early enough to cause arrest, and another that clearly was p53 independent and suggested a role for the SDI1 gene product in the maintenance rather than in the cause of inhibition of DNA synthesis. (C) 1994 Wiley-Liss, Inc. C1 BAYLOR COLL MED,HUFFINGTON CTR AGING,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC. FU NIA NIH HHS [AG P01 07123, AG11066, T32 AG00183] NR 25 TC 166 Z9 166 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1994 VL 11 IS 2 BP 59 EP 64 DI 10.1002/mc.2940110202 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA PN369 UT WOS:A1994PN36900001 PM 7522462 ER PT J AU MACE, K GONZALEZ, FJ MCCONNELL, IR GARNER, RC AVANTI, O HARRIS, CC PFEIFER, AMA AF MACE, K GONZALEZ, FJ MCCONNELL, IR GARNER, RC AVANTI, O HARRIS, CC PFEIFER, AMA TI ACTIVATION OF PROMUTAGENS IN A HUMAN BRONCHIAL EPITHELIAL-CELL LINE STABLY EXPRESSING HUMAN CYTOCHROME-P450 1A2 SO MOLECULAR CARCINOGENESIS LA English DT Article DE CARCINOGEN METABOLISM; TRANSFECTION; CYTOCHROME P450; AFLATOXIN; DNA ADDUCTS ID C-MYC PROTOONCOGENES; KI-RAS ONCOGENE; METABOLIC-ACTIVATION; NEOPLASTIC TRANSFORMATION; HEPATOCELLULAR-CARCINOMA; CHEMICAL CARCINOGENS; AFLATOXIN EXPOSURES; TRANSFERRED GENES; P53 GENE; CDNA AB Normal human bronchial epithelial (NHBE) cells are the putative progenitor cells of all types of lung cancer. NHBE cells immortalized by SV40 T-antigen retain many characteristics of the primary cells and are a useful model for investigating the role of oncogenes, tumor suppressor genes, and certain chemical carcinogens in the molecular pathogenesis of lung cancer. In this study, SV40 T-antigen-positive cells (BEAS-2B) were characterized for their metabolic functions and were shown to continue to express epoxide hydrolase, glutathione S-transferase pi, glutathione peroxidase, and catalase. To increase their metabolic activity towards human procarcinogens, human cytochrome P450 1A2 (CYP1A2) was stably expressed by introducing CYP1A2 cDNA into BEAS-2B cells either by infection with a high-titer recombinant retrovirus (pXT-1A2) or by transfection with a CYP1A2 expression vector (pCMV1A2), which produced the cell lines B-1A2 and B-CMV1A2, respectively. Cell lines established with either expression system expressed enzymatically active CYP1A2 protein and were 50- to 400-fold more sensitive to the cytotoxic effect of the carcinogen aflatoxin B-1 (AFB(1)) than the corresponding control cell lines. The cytotoxic effects of AFB(1) were paralleled by increased metabolism of AFB(1) and enhanced formation of the AFB(1)-N-7 guanine adduct in B-CMV1A2 cells. Cytotoxicity and adduct formation correlated with a significantly higher protein expression of CYP1A2 by the cytomegalovirus promoter-driven plasmid. Since this human epithelial cell line is the precursor cell type of lung cancer, has normal phase II enzymes, and exhibits highly reproducible expression of phase I enzymes, this in vitro model should aid in the evaluation of putative human carcinogens and anticarcinogens. (C) 1994 Wiley-Liss, Inc. C1 NESTLE RES CTR,CH-1000 LAUSANNE 26,SWITZERLAND. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV YORK,DEPT BIOL,JACK BIRCH UNIT ENVIRONM CARCINOGENESIS,YORK YO1 5DD,N YORKSHIRE,ENGLAND. NR 53 TC 43 Z9 44 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1994 VL 11 IS 2 BP 65 EP 73 DI 10.1002/mc.2940110203 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA PN369 UT WOS:A1994PN36900002 PM 7916994 ER PT J AU CMARIK, JL HERSCHMAN, H COLBURN, NH AF CMARIK, JL HERSCHMAN, H COLBURN, NH TI PREFERENTIAL PRIMARY-RESPONSE GENE-EXPRESSION IN PROMOTION-RESISTANT VERSUS PROMOTION-SENSITIVE JB6 CELLS SO MOLECULAR CARCINOGENESIS LA English DT Article DE NEOPLASTIC CELL TRANSFORMATION; TUMOR PROMOTERS; 12-O-TETRADECANOYLPHORBOL-13-ACETATE ID MOUSE EPIDERMAL-CELLS; SWISS 3T3 CELLS; PROTEIN-KINASE-C; MESSENGER-RNA; TUMOR PROMOTERS; PHORBOL ESTERS; GROWTH-FACTOR; NGFI-B; ANCHORAGE INDEPENDENCE; DIFFERENTIAL INDUCTION AB The 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequence (TIS) genes are a set of primary response genes induced in Swiss 3T3 cells by TPA. They include three transcription factors, a prostaglandin synthase, and three proteins of unknown function. To ascertain which, if any TIS genes might be involved in tumor promotion, we examined the expression of these genes in response to tumor promoters in transformation promotion-sensitive (P+) and -resistant (P-) JB6 murine epidermal cells, a model used to identify events relevant to promotion. A subset of TIS genes (TIS1, TIS10, and TIS21) was preferentially induced by TPA in P- cells. in addition, TIS1 and TIS21 mRNAs were preferentially induced in P- cells by epidermal growth factor, another transformation promoter that distinguishes P+ from P- cells. TIS1 and TiS21 protein levels were also greater in TPA-treated P- cells than P+ cells. Forskolin, a cAMP-elevating anti-promoter, increased TPA-induced levels of TIS1, TIS10 and TIS21 mRNAs in P+ cells, ruling in potential roles for these genes in modulating tumor promotion. The anti-promoters fluocinolone acetonide, retinoic acid, and superoxide dismutase did not enhance TPA-induced levels of TIS1 and TIS21 mRNAs in P+ cells, suggesting that these inhibitors may act on other promotion-relevant genes. TIS1 encodes a member of the steroid receptor superfamily. TIS21 encodes a protein of unknown function with strong sequence similarity to BTG1, a proposed ''anti-proliferative gene'' (Rouault JP, Rimokh R, Tessa C, et al., EMBO J 11:1663-1670, 1992). Preferential induction by multiple promoters of these TIS genes in P- cells and enhancement of their induction in P+ cells by the anti-promoter forskolin make TIS1 and TIS21 candidates for promotion suppressor genes. (C) 1994 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,INST MOLEC BIOL,BIOMED & ENVIRONM SCI LAB,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOL CHEM,LOS ANGELES,CA 90024. RP CMARIK, JL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,BLDG 560,ROOM 21-4,FREDERICK,MD 21702, USA. NR 41 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1994 VL 11 IS 2 BP 115 EP 124 DI 10.1002/mc.2940110209 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA PN369 UT WOS:A1994PN36900008 PM 7916993 ER PT J AU YANG, YL MINUCCI, S ZAND, DJ OZATO, K ASHWELL, JD AF YANG, YL MINUCCI, S ZAND, DJ OZATO, K ASHWELL, JD TI T-CELL ACTIVATION AND INCREASES IN PROTEIN-KINASE-C ACTIVITY ENHANCE RETINOIC ACID-INDUCED GENE-TRANSCRIPTION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RECEPTOR-BETA; OKADAIC ACID; PHOSPHORYLATION; DIFFERENTIATION; IMMUNODETECTION; EXPRESSION; ALPHA; IDENTIFICATION; INVOLVEMENT; DIVERSITY AB Retinoic acid (RA) has profound effects on cell growth and differentiation. Its receptors are members of the steroid/thyroid hormone receptor superfamily, which regulates nuclear transcription and gene expression by binding specific response elements. Protein kinase C (PKC) is activated during signal transduction initiated by a variety of membrane receptors. Using a RA-responsive element and reporter gene construct transfected into a T cell, we found: 1) T cell activation and PKC activators enhance transactivation by RA, 2) down-regulation of PKC protein has little effect on RA transactivation but abolishes superinduction by phorbol ester, which is restored by cotransfection of a PKC alpha-expression vector, and 3) cotransfection of dominant-negative c-jun does not prevent superinduction by phorbol ester. Together, these data demonstrate that PKC can modulate RA signal transduction, apparently without involvement of AP-1, and provide a new example of cross-talk between signal transduction pathways. C1 NCI, BIOL RESPONSE MODIFIERS PROGRAM, IMMUNE CELL BIOL LAB, BETHESDA, MD 20892 USA. NICHHD, MOLEC GROWTH REGULAT LAB, BETHESDA, MD 20892 USA. RI Minucci, Saverio/J-9669-2012 NR 45 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1994 VL 8 IS 10 BP 1370 EP 1376 DI 10.1210/me.8.10.1370 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PP922 UT WOS:A1994PP92200009 PM 7854354 ER PT J AU BENHAMOU, M BERENSTEIN, EH JOUVIN, MH SIRAGANIAN, RP AF BENHAMOU, M BERENSTEIN, EH JOUVIN, MH SIRAGANIAN, RP TI THE RECEPTOR WITH HIGH-AFFINITY FOR IGE ON RAT MAST-CELLS IS A FUNCTIONAL RECEPTOR FOR RAT IGG2A SO MOLECULAR IMMUNOLOGY LA English DT Article DE FC-EPSILON-RI; RAT MAST CELLS; RAT BASOPHILIC LEUKEMIA CELLS; IGG2A; HISTAMINE RELEASE; PROTEIN TYROSINE PHOSPHORYLATION; FC-GAMMA-R ID FC-EPSILON-RI; BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE PHOSPHORYLATION; HISTAMINE-RELEASE; GAMMA-RIII; IMMUNOGLOBULIN-E; MONOCLONAL-ANTIBODIES; HUMAN-LEUKOCYTES; EXPRESSION; ANTIGEN AB Rat mast cells express high-affinity receptors for IgE (Fc epsilon RI) and low-affinity receptors for IgG (Fc gamma R). In this study, the capacity of Ige to activate the rat basophilic leukemia (RBL-2H3) and rat peritoneal mast cells was investigated. Immune complexes formed with purified rat IgG and antigen as well as chemically cross-linked rat IgG induced histamine release from RBL-2H3 cells. This stimulation was inhibited by pre-incubation of the cells with saturating concentrations of monomeric IgE. With chemically cross-linked rat IgG of each subclass, only IgG2a stimulated histamine release from RBL-2H3 cells and this release was also inhibited by prior saturation of the Fc epsilon RI with monomeric IgE. Identical results were obtained with rat peritoneal mast cells. In binding experiments, IgE and cross-linked rat IgG2a bound to rat Fc epsilon RI transfected into CHO cells. Monomeric rat IgG2a, cross-linked rat IgG1, IgG2b, IgG2c and rabbit IgG did not bind to Fc epsilon RI. Stimulation of RBL-2H3 cells with aggregated IgG2a induced phosphorylation of tyrosines in the beta and gamma subunits of the Fc epsilon RI. Thus, although RBL-2H3 and rat peritoneal mast cells have Fc gamma R, the IgG-mediated stimulation of these cells for histamine release was by the Fc epsilon RI. Altogether, these data demonstrate that the rat Fc epsilon RI is a functional receptor with low affinity for rat IgG2a. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. RP BENHAMOU, M (reprint author), NIDR,IMMUNOL LAB,RECEPTOR & SIGNAL TRANSDUCT SECT,10-1A31,9000 ROCKVILE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 1994 VL 31 IS 14 BP 1089 EP 1097 DI 10.1016/0161-5890(94)90104-X PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA PK643 UT WOS:A1994PK64300006 PM 7523866 ER PT J AU KONKEL, ME MARCONI, RT MEAD, DJ CIEPLAK, W AF KONKEL, ME MARCONI, RT MEAD, DJ CIEPLAK, W TI IDENTIFICATION AND CHARACTERIZATION OF AN INTERVENING SEQUENCE WITHIN THE 23S RIBOSOMAL-RNA GENES OF CAMPYLOBACTER-JEJUNI SO MOLECULAR MICROBIOLOGY LA English DT Article ID GENUS CAMPYLOBACTER; ORGANIZATION; 16S AB Campylobacter jejuni is a significant cause of bacterial enteritis in humans. Three of seven C. jejuni isolates examined were found to contain fragmented 23S rRNA. The occurrence of fragmented 23S rRNA correlated with the presence of an intervening sequence (IVS) within the 23S rRNA genes. The IVS is 157 nucleotides in length and replaces an eight nucleotide sequence in the 23S rRNA genes of C. jejuni isolates that contain intact 23S rRNA. The two ends of the IVS share 31 bases of complementarity that could form a stem-loop structure. Fragmentation of the 23S ribosomal RNA results from the excision of the IVS from the transcribed RNA; the 3' cleavage site maps within the putative stem-loop formed by the IVS. Southern hybridization analysis revealed that the IVS is not present in the genomes of isolates that contain intact 23S rRNA, suggesting that the IVS is not derived from Campylobacter chromosomal sequences. The C. jejuni IVS is located at a position analogous to that of the IVSs found in both Salmonella and Yersinia spp. RP KONKEL, ME (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 26 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1994 VL 14 IS 2 BP 235 EP 241 DI 10.1111/j.1365-2958.1994.tb01284.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA PM675 UT WOS:A1994PM67500005 PM 7530317 ER PT J AU ZUBER, M HOOVER, TA POWELL, BS COURT, DL AF ZUBER, M HOOVER, TA POWELL, BS COURT, DL TI ANALYSIS OF THE RNC LOCUS OF COXIELLA-BURNETII SO MOLECULAR MICROBIOLOGY LA English DT Article ID GTP-BINDING PROTEIN; ESCHERICHIA-COLI; RNASE-III; PSEUDOMONAS-AERUGINOSA; BACTERIOPHAGE-LAMBDA; RIBONUCLEASE-III; S-POMBE; GENE; OPERON; ERA AB A 3.2 kb EcoRI genomic DNA fragment of Coxiella burnetii was isolated by virtue of its ability to suppress mucoidy in Escherichia coli. Nucleotide sequence analysis revealed the presence of the genes homologous to me, era and recO of E. coli. Suppression of capsule synthesis, measured by beta-galactosidase expression in lon(-) cps-lac fusion strains of E. coli, is caused by gene-dosage effects of the plasmid-borne me genes of either C. burnetii or E. coli. The rnc gene of C. burnetii complemented rnc(-) E. coli hosts for lambda plaque morphology and stimulation of lambda N gene expression. We also demonstrated heterologous complementation of an E. coli strain defective for the expression of Era, an essential protein in E. coli, using the plasmid-borne C. burnetii era. Under the control of the bacteriophage lambda P-L promoter, this 3.2 kb EcoRI DNA fragment directed the synthesis in E. coli of three proteins with approximate molecular masses of 35, 27 and 25 kDa. Antibodies against purified E. coli Era protein cross-reacted with the 35 kDa protein of C. burnetii on Western blots. C1 USA,MED RES INST INFECT DIS,DIV TOXICOL,FREDERICK,MD 21702. USA,MED RES INST INFECT DIS,DIV BACTERIOL,FREDERICK,MD 21702. RP ZUBER, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC CONTROL & GENET SECT,CHROMOSOME BIOL LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 43 TC 25 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1994 VL 14 IS 2 BP 291 EP 300 DI 10.1111/j.1365-2958.1994.tb01290.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA PM675 UT WOS:A1994PM67500011 PM 7830573 ER PT J AU BELLAND, RJ MORRISON, SG ISON, C HUANG, WM AF BELLAND, RJ MORRISON, SG ISON, C HUANG, WM TI NEISSERIA-GONORRHOEAE ACQUIRES MUTATIONS IN ANALOGOUS REGIONS OF GYRA AND PARC IN FLUOROQUINOLONE-RESISTANT ISOLATES SO MOLECULAR MICROBIOLOGY LA English DT Article ID COLI DNA GYRASE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; TOPOISOMERASE-IV; GENE; CHROMOSOME; SEQUENCE; CLONING; SUBUNIT; MAP AB Neisseria gonorrhoeae homologues of gyrA and parC have been identified using hybridization probes generated from conserved regions of diverse gyrA genes. These genes have been tentatively identified as gyrA and parC, based on predicted amino acid sequence homologies to known GyrA homologues from numerous bacterial species and to ParC from Escherichia coli and Salmonella typhimurium. The gyrA gene maps to a physical location distant from the gyrB locus on the gonococcal chromosome, which is similar to the situation found in E. coli. The parC gene is not closely linked (i.e. greater than 9 kb) to an identifiable parE gene in N. gonorrhoeae. The gonococcal GyrA is slightly larger than its E. coli homologue and contains several small insertions near the C-terminus of the predicted open reading frame. A series of ciprofloxacin-resistant mutants were selected by passage of N. gonorrhoeae on increasing concentrations of the antibiotic. Sequential passage resulted in the selection of isolates with minimum inhibitory concentrations approximately 10 000-fold higher than the parental strain. Mutations within gyrA resulted in low to moderate levels of resistance, while strains with high-level resistance acquired analogous mutations in both gyrA and parC. Resistance mutations were readily transferred between N. gonorrhoeae strains by transformation. The frequencies of transformation, resulting in different levels of ciprofloxacin resistance, further support the notion that both gyrA and parC genes are involved in the establishment of extreme levels of ciprofloxacin resistance. C1 ST MARYS HOSP,SCH MED,WRIGHT FLEMING INST,DEPT MED MICROBIOL,LONDON W2 1PG,ENGLAND. UNIV UTAH,MED CTR,DEPT CELLULAR VIRAL & MOLEC BIOL,SALT LAKE CITY,UT 84132. RP BELLAND, RJ (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. FU NIGMS NIH HHS [GM21960] NR 37 TC 190 Z9 205 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1994 VL 14 IS 2 BP 371 EP 380 DI 10.1111/j.1365-2958.1994.tb01297.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA PM675 UT WOS:A1994PM67500018 PM 7830580 ER PT J AU DEMORAIS, SMF WILKINSON, GR BLAISDELL, J MEYER, UA NAKAMURA, K GOLDSTEIN, JA AF DEMORAIS, SMF WILKINSON, GR BLAISDELL, J MEYER, UA NAKAMURA, K GOLDSTEIN, JA TI IDENTIFICATION OF A NEW GENETIC-DEFECT RESPONSIBLE FOR THE POLYMORPHISM OF (S)-MEPHENYTOIN METABOLISM IN JAPANESE SO MOLECULAR PHARMACOLOGY LA English DT Article ID MEPHENYTOIN HYDROXYLATION DEFICIENCY; S-MEPHENYTOIN; OXIDATION POLYMORPHISM; DEBRISOQUIN AB A genetic polymorphism in the metabolism of the anticonvulsant drug (S)-mephenytoin has been well documented in humans. There are marked interracial differences in the frequency of the poor metabolizer phenotype, which comprises 2-5% of Caucasian but 18-23% of Asian populations. We have recently reported: that the principal genetic defect responsible for the poor metabolizer phenotype is a single-base pair mutation in exon 5 of CYP2C19 (CYP2C19(m)), which accounts for similar to 75-83% of the defective alleles in both Japanese and Caucasians subjects. In the present study, we have identified a new mutation (CYP2C19(m2)) in Japanese poor metabolizers, consisting of a guanine to adenine mutation at: position 636 of exon 4 of CYP2C19, which creates a premature stop codon. Genotyping of seven Japanese poor metabolizers who were not homozygous for the previously described CYP2C19, defect (now designated CYP2C19(m1)) indicated that they were either homozygous for the new defect (CYP2C19(m2)/CYP2C19(m2)) or heterozygous (CYP2C19(m1)/CYP2C19(m2)) for the two defects. CYP2C19(m1),r accounts for 25 of 34 alleles in Japanese poor metabolizers, whereas CYP2C19(m2) accounts for the remaining nine alleles. Hence, CYP2C19(m1) and CYP2C19(m2) explain 100% of the available Japanese poor metabolizers (34 alleles). In contrast, the CYP2C19(m2) defect was not detected in nine Caucasian poor metabolizers (83% of available poor metabolizer alleles were CYP2C19(m1)), indicating the existence of another, as yet unidentified, mutation. Genetic testing of the families of two Japanese poor metabolizer probands showed that coinheritance of the CYP2C19(m1) and CYP2C19(m2) alleles was concordant with the autosomal recessive inheritance of the poor metabolizer phenotype. C1 NIEHS,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,SCH MED,DEPT PHARMACOL,NASHVILLE,TN 37232. UNIV BASEL,BIOZENTRUM,DEPT PHARMACOL,CH-4056 BASEL,SWITZERLAND. OITA MED SCH,DEPT CLIN PHARMACOL & THERAPEUT,OITA 87955,JAPAN. RI Goldstein, Joyce/A-6681-2012 FU NIGMS NIH HHS [GM-31304] NR 22 TC 587 Z9 608 U1 3 U2 15 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1994 VL 46 IS 4 BP 594 EP 598 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ538 UT WOS:A1994PQ53800002 PM 7969038 ER PT J AU LEE, JS PAULL, K ALVAREZ, M HOSE, C MONKS, A GREVER, M FOJO, AT BATES, SE AF LEE, JS PAULL, K ALVAREZ, M HOSE, C MONKS, A GREVER, M FOJO, AT BATES, SE TI RHODAMINE EFFLUX PATTERNS PREDICT P-GLYCOPROTEIN SUBSTRATES IN THE NATIONAL-CANCER-INSTITUTE DRUG SCREEN SO MOLECULAR PHARMACOLOGY LA English DT Article ID MULTIDRUG RESISTANCE GENE; TUMOR-CELL-LINES; CARCINOMA-CELLS; EXPRESSION; CYTOTOXICITY; MODULATION; MDR-1/P-GLYCOPROTEIN; TRANSPORTER; INHIBITION; PHENOTYPE AB Fifty-eight cell lines in the National Cancer Institute drug screen were analyzed for their ability to efflux the fluorescent dye rhodamine 123 as a functional assay for P-glycoprotein (Pgp). Using flow cytometry, the rhodamine fluorescence was measured for each cell line under four incubation conditions, i.e., after accumulation in the presence or absence of the Pgp antagonist cyclosporin A and after efflux in rhodamine-free medium in the presence or absence of cyclosporin A. The results in some cell lines were compatible with Pgp-mediated efflux. There was a significant correlation between mdr-1 expression and rhodamine efflux in the 58 cell lines (r = 0.788, p = 0.0001). Using the rhodamine efflux data as a seed for COMPARE analysis with the cytotoxicity data on >30,000 compounds in the National Cancer Institute drug screen database, hundreds of compounds with high correlation coefficients were identified. Selected compounds were tested for reversal of cross-resistance in a multidrug-resistant cell line. A high degree of reversibility, up to 10,000-fold, for some of the compounds was noted in the presence of the Pgp antagonist PSC 833. This finding suggested that compounds with predominately Pgp-mediated resistance were being identified. Using these compounds as seeds for COMPARE analysis against a more restricted database of 187 standard agents, a series of standard compounds were repeatedly identified as having high correlation coefficients with the newly identified Pgp substrates. These standard agents, including phyllanthoside, bisantrene, and homoharringtonine, constitute an mdr-1 profile. New agents identified as being highly correlated with these compounds may benefit from clinical trials with Pgp antagonists. C1 NCI,DIV CANC TREATMENT,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NR 38 TC 311 Z9 314 U1 0 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1994 VL 46 IS 4 BP 627 EP 638 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ538 UT WOS:A1994PQ53800007 PM 7969041 ER PT J AU BENCHEKROUN, MN SCHNEIDER, E SAFA, AR TOWNSEND, AJ SINHA, BK AF BENCHEKROUN, MN SCHNEIDER, E SAFA, AR TOWNSEND, AJ SINHA, BK TI MECHANISMS OF RESISTANCE TO ANSAMYCIN ANTIBIOTICS IN HUMAN BREAST-CANCER CELL-LINES SO MOLECULAR PHARMACOLOGY LA English DT Article ID FREE-RADICAL FORMATION; INDUCED LIPID-PEROXIDATION; P-GLYCOPROTEIN; TUMOR-CELLS; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; GLUTATHIONE-PEROXIDASE; HERBIMYCIN-A; NEU ONCOGENE; ADRIAMYCIN AB We recently reported that multidrug-resistant, P-170 glycoprotein-positive, Adriamycin-selected, human breast tumor (MCF7/ADR(R)) cells were resistant to the benzoquinonoid ansamycin antibiotics geldanamycin (GL) and herbimycin A (HA) and that significantly fewer hydroxyl radicals were formed in resistant cells. We have carried out additional studies to define the mechanisms of cytotoxicity of and resistance to GL and HA, by directly examining the interactions of these drugs with P-170 glycoprotein using photoaffinity labeling. We found that both GL and HA inhibited binding of azidopine to P-170 glycoprotein in a dose-dependent manner. We have developed a 10-fold GL-resistant cell line (MCF7/GL(R)) by continuous drug exposure. Our studies indicated no significant differences in free radical formation between wild-type MCF7 cells and MCF7/GL(R) cells. Uptake and efflux studies indicated a small decrease in the GL accumulation but no difference in the efflux of GL in these cells. Verapamil had no effect on cellular accumulation of GL in wild-type MCF7 cells or MCF7/GL(R) cells. Verapamil significantly increased the accumulation of GL in MCF7/ADR(R) cells and enhanced GL cytotoxicity 12-fold, suggesting that GL interacted with the P-170 glycoprotein. Using reverse transcription-polymerase chain reaction, we found no expression of the mdr1 gene; however, expression of the multidrug resistance-associated protein was about 2-fold higher in MCF7/GL(R) cells. Taken together, these studies indicate that the mechanisms of GL resistance are multifactorial. Although decreased free radical formation may not play a significant role in low levels of GL resistance, e.g., in MCF7/GL(R) cells, both overexpression of mdr1 and decreased free radical formation contribute to GL resistance in highly resistant cells such as MCF7/ADR(R) cells. C1 NCI,CLIN PHARMACOL BRANCH,MOLEC & BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892. NCI,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. UNIV CHICAGO,CANC RES CTR,CHICAGO,IL 60637. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27157. FU NCI NIH HHS [CA5678] NR 40 TC 23 Z9 23 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1994 VL 46 IS 4 BP 677 EP 684 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ538 UT WOS:A1994PQ53800013 PM 7969046 ER PT J AU BERGER, SP FARRELL, K CONANT, D KEMPNER, ES PAUL, SM AF BERGER, SP FARRELL, K CONANT, D KEMPNER, ES PAUL, SM TI RADIATION INACTIVATION STUDIES OF THE DOPAMINE REUPTAKE TRANSPORTER PROTEIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID D-GLUCOSE COTRANSPORTER; PHLORIZIN-BINDING; CATECHOLAMINE UPTAKE; SIZE DETERMINATION; H-3 PAROXETINE; UPTAKE SITES; TARGET SIZE; RECEPTORS; COCAINE; EXPRESSION AB Using radiation inactivation, we have estimated the target size for the neuronal dopamine transporter protein. The specific binding of several radioligands previously shown to label the dopamine transporter was determined in an irradiated striatal membrane preparation. The apparent target size of the 1-[1-(2-[H-3] benzo[b]thienyl)cyclohexyl] piperidine site was approximately 98 kDa. However, the apparent target size of the ''cocaine binding site,'' as measured with the cocaine analogue 2 beta-[H-3]carbomethoxy-3 beta-(4-fluorophenyl)tropane in the same assays, was approximately 140 kDa. Radiation inactivation of the binding of other ligands (GBR-12935 and mazindol) led to target size estimates in the same range (94 kDa and 133 kDa, respectively). All of these target sizes are significantly larger than the estimate of 70 kDa derived from the deduced amino acid sequence for the cloned dopamine reuptake transporter cDNA. Larger target sizes than expected have also been reported for ligand binding to the sodium-dependent serotonin transporter and glucose transporter. The estimated sizes for the ligand binding site(s) associated with the dopamine transporter protein are difficult to reconcile with a single transporter protein of 70 kDa. We conclude that the dopamine transporter protein is a homo- or hetero-oligomer when occupied in situ by uptake-blocking drugs like cocaine. C1 NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. NIMH,MOLEC PHARMACOL SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP BERGER, SP (reprint author), UNIV CALIF SAN FRANCISCO,VET ADM MED CTR,PSYCHIAT SERV 116M,PSYCHIAT & NEUROL LAB,SAN FRANCISCO,CA 94121, USA. FU NIDA NIH HHS [1R29-DA07376] NR 39 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1994 VL 46 IS 4 BP 726 EP 731 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ538 UT WOS:A1994PQ53800019 PM 7969052 ER PT J AU GAO, WY JOHNS, DG MITSUYA, H AF GAO, WY JOHNS, DG MITSUYA, H TI ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY OF HYDROXYUREA IN COMBINATION WITH 2',3'-DIDEOXYNUCLEOSIDES SO MOLECULAR PHARMACOLOGY LA English DT Article ID RIBONUCLEOTIDE REDUCTASE; CELLS; DIDEOXYCYTIDINE; PHOSPHORYLATION; AZIDOTHYMIDINE; DIDEOXYINOSINE; THERAPY; DNA AB The effects of hydroxyurea (HU), an inhibitor of ribonucleotide reductase, on the replication of human immunodeficiency virus type 1 (HIV-1) in activated peripheral blood mononuclear cells were studied. The inhibition of HIV-1 replication by HU alone was dose dependent, with a 90% inhibitory concentration of 0.4 mM, a plasma concentration tolerated by patients with oncological diseases. HU at lower concentrations (<0.1 mM) was found to potentiate the antiviral activity of 2',3'-dideoxyinosine (ddl), 3'-azido-2',3'-dideoxythymidine, and 2',3'-dideoxythymidine against HIV-1, with the potentiation being ddl greater than 3'-azido-2',3'-dideoxythymidine = 2',3'-dideoxycytidine. In the presence of 0.1 mM HU, the 90% inhibitory concentration of ddl was reduced by 6-fold in activated peripheral blood mononuclear cells. The potentiating effect of HU on ddl action was time dependent, with the greatest inhibition of HIV-1 growth being seen when HU was present during and after virus adsorption, i.e., apparently coinciding with the time of proviral DNA synthesis. A brief incubation of activated cells with HU and ddl at low concentrations before virus exposure reduced p24 production by >50%. Analyses using high performance liquid chromatography and enzymatic assays suggested that the greater degree of potentiation by HU of the action of ddl, compared with the other dideoxynucleosides, is due to the more effective inhibition by HU of dATP synthesis, compared with the synthesis of the other deoxynucleoside triphosphates (dGTP, dTTP, and dCTP). The present study suggests that, for appropriate agents, pharmacological reduction of deoxynucleoside triphosphate levels represents a potential therapeutic approach for inhibition of HIV-1 replication. C1 NCI,DIV CANC TREATMENT,EXPTL RETROVIROL SECT,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 24 TC 105 Z9 105 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1994 VL 46 IS 4 BP 767 EP 772 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ538 UT WOS:A1994PQ53800025 PM 7969058 ER PT J AU DESERRES, FJ MALLING, HV AF DESERRES, FJ MALLING, HV TI FORWARD-MUTATION TESTS ON THE ANTITUMOR AGENT ICR-170 IN NEUROSPORA-CRASSA DEMONSTRATE THAT IT INDUCES GENE/POINT MUTATIONS IN THE AD-3 REGION AND AN EXCEPTIONALLY HIGH-FREQUENCY OF MULTIPLE-LOCUS AD-3 MUTATIONS WITH CLOSELY LINKED SITES OF RECESSIVE LETHAL DAMAGE SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE HETEROKARYON 12; GENE/POINT MUTATIONS; MULTIPLE-LOCUS MUTATIONS; MULTILOCUS DELETION MUTATIONS; AD-3 REGION; AD-3A LOCUS; AD-3B LOCUS; RECESSIVE LETHAL MUTATIONS; ICR-170; ANTITUMOR AGENT ID GENE POINT MUTATIONS; 2-COMPONENT HETEROKARYONS; RISK ASSESSMENT; SPECIFICITY; SPECTRA; ASSAY AB The mutagenicity of the antitumor agent ICR-170 (2-methoxy-6-chloro-9-[(ethyl-2-chloroethyl)amino propyl-amino] acridine dihydrochloride) in the adenine-3 (ad-3) region was studied with a two-component heterokaryon (H-12) of Neurospora crassa. The objective was to characterize the genetic damage produced by this acridine nitrogen mustard derivative to determine in a lower eukaryotic organism the basis for its potent activity against ascites tumors in mice. As in higher eukaryotes, specific-locus mutations in the ad-3 region of strain H-12 result from gene/point mutations, multiple-locus mutations, and multilocus deletion mutations at the closely linked ad-3A and ad-3B loci. Six different treatments of conidial suspensions of H-12 with ICR-170 were used to obtain dose-response curves for inactivation of conidia as well as the overall induction of ad-3 forward mutations using a direct method based on pigment accumulation rather than a requirement for adenine. These experiments demonstrated that: (1) the slope of the dose-response curve for ICR-170-induced specific-locus mutations in the ad-3 region was 1.97 +/- 0.02, and (2) ICR-170 is a potent mutagen (maximum forward-mutation frequency between 1000 and 10 000 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Both biochemical and classical genetic tests were used to characterize the ICR-170-induced ad-3 mutations from each of the six treatments to distinguish the different genotypic classes and subclasses. The overall data base demonstrates that ICR-170-induced ad-3 mutations result exclusively from gene/point mutations at the ad-3A and ad-3B loci and not multilocus deletion mutations. In addition, the frequency of multiple-locus ad-3 mutations resulting from gene/point mutations at the ad-3A and ad-3B loci with a separate site of recessive lethal damage elsewhere in the genome increases as a function of dose. However, an exceptionally high frequency of multiple-locus ad-3 mutations consisting of gene/point mutations at the ad-3A and ad-3B loci with a separate site of closely linked recessive lethal damage was found at all doses. Comparison of the dose-response curves for the major classes and subclasses of ICR-170-induced ad-3 mutations demonstrates that the gene/point ad-3 mutations and multiple-locus ad-3 mutations with a separate site of recessive lethal damage elsewhere in the genome have different induction kinetics. The potent mutagenic activity of this potent antitumor agent ICR-170 is contrasted with the mutagenic activity of known chemical carcinogens using similar tests in Neurospora. C1 NIEHS,DIV INTRAMURAL RES,GENET LAB,RES TRIANGLE PK,NC 27709. RP DESERRES, FJ (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 1 PY 1994 VL 310 IS 1 BP 15 EP 36 DI 10.1016/0027-5107(94)90005-1 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA PM081 UT WOS:A1994PM08100002 PM 7523879 ER PT J AU SPENCER, DL CASPARY, WJ AF SPENCER, DL CASPARY, WJ TI IN-SITU AND SUSPENSION PROTOCOLS FOR CHEMICALLY-INDUCED MUTATION AT THE TK LOCUS IN L5178Y MOLY CELLS - DOSE-RESPONSE AND COLONY SIZE DISTRIBUTION SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE MUTATION ASSAY; L5178Y MOUSE LYMPHOMA CELL; SMALL AND LARGE COLONIES; IN SITU PROTOCOL; SUSPENSION PROTOCOL; EMS (ETHYL METHANESULFONATE) ID MOUSE LYMPHOMA-CELLS; THYMIDINE KINASE LOCUS; TRIFLUOROTHYMIDINE-RESISTANT; MAMMALIAN-CELLS; ASSAY SYSTEM; CHROMOSOME ANALYSIS; MUTAGENESIS ASSAY; VALIDATION; MUTANTS; TFT AB We used EMS up to concentrations of 0.25 mu l/ml (292 mu g/ml) to induce mutations at the tk locus in L5178Y MOLY cells, measured the cellular response by the in situ mutation assay protocol and compared these results to those obtained in a concomitant suspension assay. EMS induced mutagenic responses with both protocols. The mutant fraction for the solvent control was 89 mutants per million viable colonies for the suspension protocol and 426 mutations per million viable cells plated for the in situ protocol. These numbers increase to 447 and 2073 respectively, with 0.25 mu l/ml EMS treatment. Sizing curves indicated that the in situ protocol detected a greater proportion of smaller colonies than did the suspension protocol. Not only were the number of small colonies greater than large colonies in the in situ protocol, but their rate of increase was also slightly higher than that of the large colonies. The in situ protocol also reduces the time and cost of experimentally performing the assay compared to the suspension protocol. In this paper we compare the use of the suspension and in situ protocols to measure chemically-induced mutations and demonstrate that the latter method detects a larger fraction of induced mutations at the fk locus in L5178Y MOLY cells. RP SPENCER, DL (reprint author), NIH,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD OCT PY 1994 VL 322 IS 4 BP 291 EP 300 DI 10.1016/0165-1218(94)90105-8 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA PM072 UT WOS:A1994PM07200008 PM 7523923 ER PT J AU ROUTLEDGE, MN MIRSKY, FJ WINK, DA KEEFER, LK DIPPLE, A AF ROUTLEDGE, MN MIRSKY, FJ WINK, DA KEEFER, LK DIPPLE, A TI NITRITE-INDUCED MUTATIONS IN A FORWARD MUTATION ASSAY - INFLUENCE OF NITRITE CONCENTRATION AND PH SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE SODIUM NITRITE; PH; SHUTTLE VECTOR; MUTATION; SUPF GENE ID CROSS-LINKED NUCLEOSIDES; SHUTTLE VECTOR PLASMID; NITROUS-ACID; DEOXYRIBONUCLEIC-ACID; ESCHERICHIA-COLI; NITRATE; MODEL; CELLS; GENE; DNA AB The mutagenicity of sodium nitrite at three pHs (7.4, 6.4 and 5.4) has been investigated by treating a shuttle vector plasmid in vitro and assaying for mutations within the supF target gene following replication of the damaged plasmid in human Ad293 cells. Mutation frequency increased with increasing nitrite concentration and decreasing pH. Among treatments from which a significant number of mutants could be collected, the most commonly induced mutations were GC --> AT transitions (44-56% of total mutations), followed by GC --> TA transversions (24-30%). The types of mutations induced at different nitrite concentrations and different pH's were similar, though some differences in their distribution throughout the supF gene were noted. These results provide information on the types of mutations that may be produced following the processing of nitrite-induced DNA damage in human cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-74101] NR 27 TC 24 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD OCT PY 1994 VL 322 IS 4 BP 341 EP 346 DI 10.1016/0165-1218(94)90110-4 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA PM072 UT WOS:A1994PM07200013 PM 7523928 ER PT J AU GUAN, XY MELTZER, PS DALTON, WS TRENT, JM AF GUAN, XY MELTZER, PS DALTON, WS TRENT, JM TI IDENTIFICATION OF CRYPTIC SITES OF DNA-SEQUENCE AMPLIFICATION IN HUMAN BREAST-CANCER BY CHROMOSOME MICRODISSECTION SO NATURE GENETICS LA English DT Article ID HOMOGENEOUSLY STAINING REGIONS; CELL-LINES; INSITU HYBRIDIZATION; MALIGNANT-MELANOMA; RAPID GENERATION; CARCINOMAS; ABNORMALITIES; ONCOGENE; DISEASE; PROBES AB We have performed microdissection of 16 putative homogeneously staining regions (hsrs) from nine different breast cancer cell lines in order to determine their chromosomal origin and composition. As expected, the most commonly amplified chromosomal band-region was 17q12 (containing ERBB2). However, regions not containing known oncogenes were also identified, including 13q31 (5/9 cases) and 20q12-13.2 (4/9 cases). The chromosomal composition of the integrated amplified DNA within each hsr was determined and in 13/16 cases (81%), hsrs were shown to be composed of two or more chromosomal regions. These studies shed light on the mechanism of formation of hsrs, and identify chromosomal regions likely to harbour genes amplified in breast cancer. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV ARIZONA,ARIZONA COMPREHENS CANC CTR,TUCSON,AZ 85719. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCI NIH HHS [CA-23074, CA-41183] NR 30 TC 132 Z9 136 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1994 VL 8 IS 2 BP 155 EP 161 DI 10.1038/ng1094-155 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PL123 UT WOS:A1994PL12300017 PM 7842014 ER PT J AU KALER, SG GALLO, LK PROUD, VK PERCY, AK MARK, Y SEGAL, NA GOLDSTEIN, DS HOLMES, CS GAHL, WA AF KALER, SG GALLO, LK PROUD, VK PERCY, AK MARK, Y SEGAL, NA GOLDSTEIN, DS HOLMES, CS GAHL, WA TI OCCIPITAL HORN SYNDROME AND A MILD MENKES PHENOTYPE ASSOCIATED WITH SPLICE-SITE MUTATIONS AT THE MNK LOCUS SO NATURE GENETICS LA English DT Article ID LINKED CUTIS LAXA; CANDIDATE GENE; NONSENSE MUTATIONS; DISEASE; ENCODES; ATPASE AB We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV ALABAMA,SCH MED,DEPT PEDIAT,BIRMINGHAM,AL 35233. RP KALER, SG (reprint author), NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BLDG 10,ROOM 9S-242,BETHESDA,MD 20892, USA. RI Segal, Neil/B-2049-2008 OI Segal, Neil/0000-0002-8294-080X NR 29 TC 169 Z9 170 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1994 VL 8 IS 2 BP 195 EP 202 DI 10.1038/ng1094-195 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA PL123 UT WOS:A1994PL12300023 PM 7842019 ER PT J AU PATEL, MN PEOPLES, RW YIM, GKW ISOM, GE AF PATEL, MN PEOPLES, RW YIM, GKW ISOM, GE TI ENHANCEMENT OF NMDA-MEDIATED RESPONSES BY CYANIDE SO NEUROCHEMICAL RESEARCH LA English DT Article DE CYANIDE; NMDA RECEPTOR; HIPPOCAMPAL CELL CULTURE; CYTOSOLIC FREE CALCIUM ID D-ASPARTATE RECEPTORS; HIPPOCAMPAL CULTURES; CHANNEL COMPLEX; MK-801 BINDING; RAT-BRAIN; GLUTAMATE; NEUROTOXICITY; ENERGY; INHIBITION; ELEVATION AB The effect of cyanide on NMDA-activated ion current and MK801 binding was studied in cultured rat hippocampal neurons. In microfluorometric analysis using fura-2, removal of extracellular Mg2+ resulted in a five-fold increase in NMDA-induced peak of [Ca2+](i). One mM NaCN enhanced the peak NMDA responses in the presence, but not in the absence of extracellular Mg2+. Cyanide enhanced the immediate rise in [Ca2+](i) produced by NMDA, followed over a 1-5 min period by a gradual increase of [Ca2+](i). Similar results were obtained in whole-cell patch clamp recordings from hippocampal neurons. One mM KCN enhanced the NMDA-activated current in the presence, but not in the absence of extracellular Mg2+. This effect was independent of cyanide-mediated metabolic inhibition since the recording pipette contained ATP (2 mM). In binding assays NaCN (1 mM) increased the binding affinity of [H-3]MK-801 to rat forebrain membranes in the presence of Mg2+, whereas in the absence of Mg2+, NaCN did not influence binding. These results indicate that cyanide enhances NMDA-mediated Ca2+ influx and inward current by interacting with the Mg2+ block of the NMDA receptor. The effect of cyanide can be explained by an initial interaction with the Mg2+ block of the NMDA receptor/ionophore which appears to be energy-independent, followed by a gradual increase in Ca2+ influx resulting from cellular energy reserve depletion. C1 PURDUE UNIV,DEPT PHARMACOL & TOXICOL,W LAFAYETTE,IN 47907. NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,PHYSIOL SECT,ROCKVILLE,MD 20852. FU NIEHS NIH HHS [ES04140] NR 22 TC 21 Z9 21 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD OCT PY 1994 VL 19 IS 10 BP 1319 EP 1323 DI 10.1007/BF01006824 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PQ733 UT WOS:A1994PQ73300015 PM 7534385 ER PT J AU POST, RM SILBERSTEIN, SD AF POST, RM SILBERSTEIN, SD TI SHARED MECHANISMS IN AFFECTIVE-ILLNESS, EPILEPSY, AND MIGRAINE SO NEUROLOGY LA English DT Article; Proceedings Paper CT Neurologic and Psychiatric Comorbidity with Migraine-Consultants Meeting CY OCT 29-30, 1993 CL NAPLES, FL ID FOS MESSENGER-RNA; CORTICOTROPIN-RELEASING HORMONE; CONTINGENT TOLERANCE; SIGNAL TRANSDUCTION; LIMBIC STRUCTURES; PROTEIN-KINASE; RAT-BRAIN; CARBAMAZEPINE; AMYGDALA; EXPRESSION AB For a specific subgroup of patients with migraine or affective illness who experience illness progression and drug tolerance, the amygdala kindling paradigm can be a useful, but nonhomologous, model. Although these patients do not have a seizure or seizure-like disorder, kindling has been used to examine the types of memory-like mechanisms that could underlie syndrome evolution in both migraine and affective illness. While the precipitants, symptomatology, duration of attack, and aura symptoms differ among epilepsy, migraine, and the affective disorders, all are paroxysmal dysregulations that partially share effective drug treatment. The principles of seizure progression presented here may apply to affective and migraine patients whose episodes progress from isolated and intermittent to more chronic or daily. These patients may also develop tolerance to long-term prophylactic treatments. C1 TEMPLE UNIV,SCH MED,PHILADELPHIA,PA 19122. GERMANTOWN HOSP & MED CTR,PHILADELPHIA,PA. RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 72 TC 28 Z9 28 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1994 VL 44 IS 10 SU 7 BP 37 EP 47 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA PT281 UT WOS:A1994PT28100007 ER PT J AU CLARK, K DINSMORE, S GRAFMAN, J DALAKAS, MC AF CLARK, K DINSMORE, S GRAFMAN, J DALAKAS, MC TI A PERSONALITY PROFILE OF PATIENTS DIAGNOSED WITH POSTPOLIO SYNDROME SO NEUROLOGY LA English DT Article ID POLIOMYELITIS AB Post-polio syndrome (PPS) refers to the late development of new neuromuscular symptoms in previously stable poliomyelitis patients. Whether psychological disturbance plays a role in the manifestation of symptoms in these patients is unclear. We examined 22 patients fulfilling the clinical criteria for PPS with the Minnesota Multiphasic Personality Inventory-II (MMPI-II), Beck Depression Inventory, Spielberger State-Trait Anxiety Scales, Chapman and Chapman Psychosis-Proneness Scales, Fatigue Scales, a neurobehavioral rating scale, and Cognitive Symptoms Self-Report Scales, The overwhelming majority of scale scores were within normal limits, and there was no indication that psychopathologic symptoms were associated with the development or severity of new muscle weakness in PPS patients. Women with PPS had significantly more somatic complaints, but were less socially isolated than men with PPS. This study confirms that the development or severity of new muscle weakness in carefully diagnosed PPS patients is not due to, or influenced by, underlying psychopathology. C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. OI Grafman, Jordan H./0000-0001-8645-4457 NR 15 TC 16 Z9 18 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1994 VL 44 IS 10 BP 1809 EP 1811 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA PL591 UT WOS:A1994PL59100009 PM 7936226 ER PT J AU NICHELLI, P APPOLLONIO, I CLARK, K GRAFMAN, J AF NICHELLI, P APPOLLONIO, I CLARK, K GRAFMAN, J TI WORD-FREQUENCY MONITORING IN PARKINSON DISEASE - AN ANALYSIS OF ACCURACY AND PRECISION SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE MEMORY; JUDGMENT OF FREQUENCY; AUTOMATIC ENCODING; PARKINSONS DISEASE ID EFFORTFUL; MEMORY AB The judgment of frequency of occurrence of stimuli appearing in a task is a complicated decision. This decision can be independently analyzed using estimates of subject accuracy (where their estimate resembles the true frequency of the stimuli) and precision (sensitive to response bias). In this study, the accuracy and precision of Parkison's disease (PD) patients estimates of the frequency of occurrence of word stimuli were analyzed. The results indicated that the accuracy estimates of PD patients were not significantly different from normal controls whereas their precision of frequency judgments was impaired. Poorer precision scores were associated with fewer categories achieved on the Wisconsin Card Sorting Test. Using accuracy and precision estimates should improve the characterization of the cognitive processes required in frequency judgments. C1 NINCDS,COGNIT NEUROSCI SECT,BLDT 10,RM 5S209,10 CTR DR,MSC 1440,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. UNIV MODENA,NEUROL CLIN,I-41100 MODENA,ITALY. UNIV MILAN,NEUROL CLIN 5,I-20122 MILAN,ITALY. RI Nichelli, Paolo/F-7336-2015; OI Nichelli, Paolo/0000-0001-9756-6796; Grafman, Jordan H./0000-0001-8645-4457 NR 22 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD OCT PY 1994 VL 7 IS 4 BP 289 EP 294 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA PY002 UT WOS:A1994PY00200007 ER PT J AU KATZ, MM MAAS, JW FRAZER, A KOSLOW, SH BOWDEN, CL BERMAN, N SWANN, AC STOKES, PE AF KATZ, MM MAAS, JW FRAZER, A KOSLOW, SH BOWDEN, CL BERMAN, N SWANN, AC STOKES, PE TI DRUG-INDUCED ACTIONS ON BRAIN NEUROTRANSMITTER SYSTEMS AND CHANGES IN THE BEHAVIORS AND EMOTIONS OF DEPRESSED-PATIENTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ANTIDEPRESSANTS; NEUROTRANSMITTERS; CSF METABOLITES; BEHAVIOR; ANXIETY ID BRANCH COLLABORATIVE PROGRAM; CEREBROSPINAL-FLUID; BIOLOGICAL COMPONENT; PLASMA-LEVELS; AMITRIPTYLINE; METABOLITES; IMIPRAMINE; SEROTONIN; PSYCHOBIOLOGY; METHODOLOGY AB Despite cumulative evidence that the tricyclic drugs result in significant changes in the functioning of brain serotonergic (5-HT) and nordrenergic (NE) systems, such changes have not been found to be associated with recovery from depression. Based upon evidence that the 5-HT anti NE systems were associated with different emotions, it was hypothesized that changes in these systems were associated with different components of behavior in drug-responsive patients and not with changes in the ''whole'' disorder. Findings from this multihospital study of 104 unipolar and bipolar depressed patients showed early drug-associated reductions in anxiety and hostility in treatment responders to precede changes in motor retardation and depressed mood. Adopting this approach of looking for relationships between changes in components of major depression and changes in neurotransmitter system function, decreases in 5-HT and NE metabolite concentrations in cerebrospinal fluid (CSF) in patients treated with tricyclics, were found to be correlated with changes in specific behaviors. Results indicated the following: (1) drug-induced changes in the 5-HT system to be associated with mood aspects, notably anxiety, and depressed mood; changes in NE primarily with the psychomotor, secondarily with the mood components of the depressed state; (2) the pattern of relationships between changes in 5-HT and in mood in the unipolar was different than that in the bipolar subtype. The results indicate that in determining the relationships of biochemical changes to behavioral ones, that it is important to take into account the type of depression (bipolar or unipolar), as well as examining individually and over time those components that make up the disorder of depression. These results support evidence that tricyclics have multiple behavioral actions, that response is mediated through changes in specific behaviors and that this approach warrants further application in prospective studies of antidepressant drug mechanisms and their therapeutic actions. C1 MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT PSYCHIAT,BRONX,NY. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. NIMH,DEPT NEUROSCI & BEHAV SCI,ROCKVILLE,MD. UNIV CALIF LOS ANGELES,HARBOR MED CTR,LOS ANGELES,CA 90024. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,HOUSTON,TX. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. FU NIMH NIH HHS [U01 MH26977, U01 MH26975, U01 MH26976] NR 39 TC 36 Z9 36 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 1994 VL 11 IS 2 BP 89 EP 100 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PM151 UT WOS:A1994PM15100002 PM 7530963 ER PT J AU FAN, P WEIGHT, FF AF FAN, P WEIGHT, FF TI THE EFFECT OF ATROPINE ON THE ACTIVATION OF 5-HYDROXYTRYPTAMINE(3) CHANNELS IN RAT NODOSE GANGLION NEURONS SO NEUROSCIENCE LA English DT Article ID MEDIATED ION CURRENT; 5-HT3 RECEPTORS; SYNAPTIC CURRENTS; ETHANOL POTENTIATION; RADIOLIGAND BINDING; NEUROBLASTOMA-CELLS; KINETIC-ANALYSIS; PHARMACOLOGY; ANTAGONISTS; RABBIT AB It has been suggested that changes in brain 5-hydroxytryptamine(3) receptor function may contribute to some behavior disorders, such as anxiety, schizophrenia and drug abuse. We are using the whole-cell version of the patch-clamp technique to study the function of 5-hydroxytryptamine(3) channels in neurons freshly dissociated from rat nodose ganglion. In these cells, 5-hydroxytryptamine elicits an inward current over the concentration range of 0.25-100 mu M (EC(50) = 2.62 mu M) by activating 5-hydroxytryptamine(3) receptors. The muscarinic cholinergic antagonist atropine reduced the amplitude of 5-hydroxytryptamine activated inward current in a concentration-dependent manner. Other muscarinic antagonists, scopolamine, dexetimide, the M1 muscarinic receptor antagonist pirenzepine, the M(2), receptor antagonist methoctramine and the M(3) receptor antagonist 4-DAMP methiodide also inhibited 5-hydroxytryptamine-induced inward current. Atropine did not appear to change the reversal potential of this current. In the presence of 5 mu M atropine, the concentration-response curve for 5-hydroxytryptamine current was shifted to the right in a parallel fashion. The EC(50) value for 5-hydroxytryptamine was increased from 2.62 to 8.76 mu M. Schild plots of increasing atropine and 5-hydroxytryptamine concentrations revealed a pA(2) value of 5.74 for atropine (apparent K-D = 1.8 mu M). These observations suggest that atropine competitively antagonizes the activation of a receptor for the neurotransmitter serotonin, a novel action of muscarinic antagonists in the nervous system. This effect of atropine may contribute to the clinical symptoms seen in severe atropine intoxication. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 47 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1994 VL 62 IS 4 BP 1287 EP 1292 DI 10.1016/0306-4522(94)90360-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PN544 UT WOS:A1994PN54400025 PM 7531305 ER PT J AU JEONG, JM KINUYA, S PAIK, CH SAGA, T SOOD, VK CARRASQUILLO, JA NEUMANN, RD REYNOLDS, JC AF JEONG, JM KINUYA, S PAIK, CH SAGA, T SOOD, VK CARRASQUILLO, JA NEUMANN, RD REYNOLDS, JC TI APPLICATION OF HIGH-AFFINITY BINDING CONCEPT TO RADIOLABEL AVIDIN WITH TC-99M LABELED BIOTIN AND THE EFFECT OF PI ON BIODISTRIBUTION SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; STREPTAVIDIN; TUMOR; PROTEINS; ELISA AB In order to label avidin with Tc-99m, we took advantage of the high affinity binding of biotin to avidin; we radiolabeled a biotin derivative with Tc-99m and then bound this Tc-99m labeled biotin derivative to avidin. For our labeling approach, N epsilon-biotinyl-L-lysine (Biocytin) was reacted with the N-hydroxy-succinimide ester of benzoylmercaptoacetyltriglycine (Bz-MAG3). The resulting Bz-MAG3-Biocytin was labeled with Tc-99m using Tc-99m glucarate as a Tc-99m transchelating agent and mixed with avidin at a 1:1 molar ratio resulting in almost a quantitative labeling yield. Tc-99m-MAG3-Biocytin/Avidin was stable in serum at 37 degrees C with 97 and 95% of the total Tc-99m activity still bound to avidin at 2 and 24 h, respectively. The biodistribution of Tc-99m-MAG3-Bio-cytin/Avidin in normal Balb/c mice showed a high liver and kidney uptake with 56.6 and 28.9%, respectively at 10 min. We attempted to lower the liver and the kidney activities by reducing the isoelectric point (pI) of avidin by conjugating succinic acid moieties at lysine residues of avidin (pI 10). The kidney uptake decreased to 19.0, 3.1 and 1.7% when the pI of avidin was reduced to 7.0-9.3, 5.5-6.2 and 4.0-4.8, respectively. The lowering of the pI, however, did not change the liver activity appreciably. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. RI Sood, Vinay/B-7109-2008; Carrasquillo, Jorge/E-7120-2010; Jeong, Jae Min/E-2102-2012; OI Jeong, Jae Min/0000-0003-2611-6020; Carrasquillo, Jorge/0000-0002-8513-5734 NR 25 TC 21 Z9 22 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 1994 VL 21 IS 7 BP 935 EP 940 DI 10.1016/0969-8051(94)90082-5 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PL578 UT WOS:A1994PL57800005 PM 9234347 ER PT J AU RARICK, TL AF RARICK, TL TI TIMING OF THE POSTPARTUM PAPANICOLAOU SMEAR - REPLY SO OBSTETRICS AND GYNECOLOGY LA English DT Letter ID ATYPICAL CERVICAL CYTOLOGY RP RARICK, TL (reprint author), NICHHD,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1994 VL 84 IS 4 BP 638 EP 639 PN 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PJ351 UT WOS:A1994PJ35100033 ER PT J AU ZENKLUSEN, JC OSHIMURA, M BARRETT, JC CONTI, CJ AF ZENKLUSEN, JC OSHIMURA, M BARRETT, JC CONTI, CJ TI INHIBITION OF TUMORIGENICITY OF A MURINE SQUAMOUS-CELL CARCINOMA (SCC) CELL-LINE BY A PUTATIVE TUMOR-SUPPRESSOR GENE ON HUMAN-CHROMOSOME-7 SO ONCOGENE LA English DT Article ID IDENTIFICATION; EXPRESSION; DELETION; CANCER; NEUROFIBROMATOSIS; HETEROZYGOSITY; CLONING; DISEASE; HYBRIDS; GROWTH AB Alterations in oncogenes and tumor suppressor genes (TSG) are considered to be critical steps in oncogenesis. However information on putative TSG involved in the developement of squamous cell carcinomas (SCC) is very limited. In this study we confirmed the existence of a tumor suppressor gene (TSG) on human chromosome 7 (hchr 7) that suppresses the tumorigenicity of squamous cell carcinomas (SCCs). We injected seven clones of CH72 cells (a murine SCC-derived cell line) bearing a hchr 7 (CH72/hchr 7) introduced by microcell fusion, two clones bearing human chromosome 12 (CH72/hchr 12) and parental CH72 cells into athymic Balb/c nude mice. The sizes of the tumors were determined twice a week until tumors reached 12 mm diameter. In situ hybridization for centromeric repetitive sequences of the transferred chromosomes were performed on the cell lines injected and the tumors arising after the injection. Southern blots and polymerase chain reaction (PCR) amplifications of near terminal sequences and (CA) microsatellite repeats were done to test the integrity of the introduced chromosomes. Five out of seven CH72/ hchr 7 clones had a twofold and threefold longer latency periods than CH72 cells. The remaining CH72/hchr 7 clones (MF 6 and 13 no. 4) had latency periods similar to that of parental CH72; MF 6 had a deletion in the introduced chromosome 7 involving q31.3-q31.3, whereas the other hybrid (MF 13 no. 4) seemed to have an intact hchr 7. Tumor-derived cells from CH72/hchr 7 hybrids with a delayed latency had lost centromeric and telomeric sequences of Chr 7. In constrast, tumors derived from the MF 6 and MF 13 no. 4 as well as the CH72/hchr 12 clones retained the introduced human chromosome as shown by chromosome 7 or 12 centromeric and telomeric sequences. These results indicate that the tumorigenicity of CH72 murine SCC cells was suppressed by hchr 7 and that the CH72/hchr 7 regain the tumorigenic phenotype after loss of the introduced chromosome, suggesting the presence of a TSG on hchr 7. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DIV RES,SMITHVILLE,TX 78957. TOTTORI UNIV,SCH LIFE SCI,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI,JAPAN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA53123] NR 37 TC 47 Z9 47 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 2817 EP 2825 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200007 PM 8084587 ER PT J AU ROMANO, A WONG, WT SANTORO, M WIRTH, PJ THORGEIRSSON, SS DIFIORE, PP AF ROMANO, A WONG, WT SANTORO, M WIRTH, PJ THORGEIRSSON, SS DIFIORE, PP TI THE HIGH TRANSFORMING POTENCY OF ERBB-2 AND RET IS ASSOCIATED WITH PHOSPHORYLATION OF PAXILLIN AND A 23 KDA PROTEIN SO ONCOGENE LA English DT Article ID GROWTH-FACTOR RECEPTOR; GUANINE-NUCLEOTIDE EXCHANGE; DNA-BINDING PROTEINS; NIH 3T3 CELLS; SIGNAL-TRANSDUCTION; TYROSINE KINASE; EGF RECEPTOR; INTERFERON-GAMMA; ADAPTER PROTEIN; RAS AB Two-dimensional gel maps of proteins phosphorylated by the epidermal growth factor receptor (EGFR) and erbB-2 kinases were obtained, to investigate the molecular basis of the different biological properties of these two molecules. Several proteins were phosphorylated by EGFR or erbB-2 with different stoichiometry. Differences were either quantitative or qualitative. In NIH3T3 cells, erbB-2 is 100-fold more transforming than EGFR. In the same cell line several proteins were preferentially phosphorylated by erbB-2, as compared to EGFR. To identify which of these substrates might be directly involved in mitogenic signaling, we obtained two-dimensional maps of proteins phosphorylated on tyrosine by EGFR/ret and an EGFR/erbB-2(TK) chimeric receptors. Both these chimerae behaved indistinguishably from erbB-2 in a number of bioassays and potently transformed NIH3T3 cells. Paxillin and a 23 kDa substrate were invariably phosphorylated to higher stoichiometry whenever potent mitogenic and transforming signals were activated. We propose that paxillin and the 23 kDa substrate are important elements in the erbB-2 and ret-activated mitogenic and transforming signaling. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. CNR,CTR ENDOCRINOL & ONCOL SPERIMENTALE,I-80125 NAPLES,ITALY. FAC MED & CHIRURG NAPLES,DIPARTIMENTO BIOL & PATOL CELLULARE & MOLEC L CAL,NAPLES,ITALY. FAC MED & CHIRURG BARI,IST MICROBIOL,BARI,ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 50 TC 21 Z9 21 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 2923 EP 2933 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200018 PM 7916147 ER PT J AU SAEZ, R CHAN, AML MIKI, T AARONSON, SA AF SAEZ, R CHAN, AML MIKI, T AARONSON, SA TI ONCOGENIC ACTIVATION OF HUMAN R-RAS BY POINT MUTATIONS ANALOGOUS TO THOSE OF PROTOTYPE H-RAS ONCOGENES SO ONCOGENE LA English DT Article ID GROWTH-FACTOR; NIH3T3 FIBROBLASTS; GENE-PRODUCT; KINASE; RAF-1; TRANSFORMATION; EXPRESSION; CELLS; PROTEINS AB R-ras, K-rev-1/rap and TC21, are more closely related to prototype H-vas than any other known members of the vas superfamily. We recently isolated a mutationally activated TC21 oncogene from a human ovarian carcinoma cell line. Based upon these observations, we sought to re-examine the transforming potential of R-ras, which was reported earlier to lack transforming capacity. Mutations were introduced into the R-uas gene at codons 38 or 87, analogous to positions 12 and 61, respectively, responsible for H-ras oncogene activation. While both mutations resulted in acquisition of R-ras transforming capacity for NIH3T3 cells the position 61 was shown to be more active. Transfectants expressing either R-ras mutant formed colonies in soft agar and were tumorigenic in vivo. As has been reported for H-ras, R-ras cooperated with c-raf-1 in inducing transformation of NIH3T3 cells. These results imply interactions in R-ras and c-raf-1 signaling pathways. We observed R-ras transcripts of 4.6 and 1.2 kb ubiquitously expressed in each of a variety of tissues examined. All these findings raise the possibility that R-ras, like prototype vas genes, may be mutationally activated as an oncogene in some human malignancies. C1 MT SINAI MED CTR,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 30 TC 75 Z9 75 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 2977 EP 2982 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200024 PM 8084601 ER PT J AU HUPPI, K SIWARSKI, D DOSIK, J MICHIELI, P CHEDID, M REED, S MOCK, B GIVOL, D MUSHINSKI, JF AF HUPPI, K SIWARSKI, D DOSIK, J MICHIELI, P CHEDID, M REED, S MOCK, B GIVOL, D MUSHINSKI, JF TI MOLECULAR-CLONING, SEQUENCING, CHROMOSOMAL LOCALIZATION AND EXPRESSION OF MOUSE P21 (WAF1) SO ONCOGENE LA English DT Note ID GENE; INHIBITOR; PROTEIN; KINASES AB The recent discovery that expression of Waf1 (p21), an inhibitor of cyclin-dependent kinases, is induced by the tumor suppressor p53 provides an important linkage between growth suppression and the cell cycle. We report here the cloning and sequencing of a mouse p21 cDNA that contains the entire coding region. Hybridization of the mouse p21 probe in Southern blot analyses confirms that p21 is a single-copy gene and that the corresponding locus, Waf1, lies proximal to H-2 on mouse chromosome 17. In northern analyses, the expression of p21 is found in most normal mouse tissues, but a surprising lack of correlation is found. between mRNA levels of p21 and p53. In order to determine which regions of p21 are most evolutionarily conserved, we have compared the cDNA sequences for the entire p21 coding region in 13 different mouse strains or species and the human p21 sequence. We conclude that two regions (corresponding to human codons 21-60 and 130-164) are strongly conserved in p21 and that these regions may represent domains that are especially critical to a functional p21 protein. C1 SCRIPPS RES INST, LA JOLLA, CA 92037 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP HUPPI, K (reprint author), NCI, GENET LAB, BLDG 37, BETHESDA, MD 20892 USA. RI Michieli, Paolo/A-2588-2011 NR 18 TC 92 Z9 94 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 3017 EP 3020 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200030 PM 8084607 ER PT J AU CHEDID, M MICHIELI, P LENGEL, C HUPPI, K GIVOL, D AF CHEDID, M MICHIELI, P LENGEL, C HUPPI, K GIVOL, D TI A SINGLE NUCLEOTIDE SUBSTITUTION AT CODON-31 (SER/ARG) DEFINES A POLYMORPHISM IN A HIGHLY CONSERVED REGION OF THE P53-INDUCIBLE GENE WAF1/CIP1 SO ONCOGENE LA English DT Note ID CYCLIN-DEPENDENT KINASES; EXPRESSION; INHIBITOR; GROWTH; CELLS; P21 AB The recently discovered WAF1/CTP1 gene is a mediator of p53 tumor suppressor activity. To analyse WAF1/ CIP1 for possible mutations, polymerase chain reaction (PCR) amplified cDNAs from several tumor cell lines were cloned and sequenced. A single point mutation which changes codon 31 from AGC to AGA (Ser to Arg) was found. This change resulted in the loss of a Bpu1102I and gain of an Esp3I restriction site, allowing for rapid screening of this mutation in human DNAs. Analysis of genomic DNAs from 50 randomly selected individuals revealed that this base pair substitution represents a polymorphism with an allelic frequency of 0.14. Transfection studies demonstrated that the expression of the Arg allele of WAF1/CIP1 was not associated with loss of tumor suppressor activity. Moreover, screening of 22 tumor DNA samples revealed no association between the tumor phenotype and the Arg allele of WAF1/CIP1 (two out of 22 tumor DNAs contained the Arg31 allele). This polymorphism will be a useful molecular marker in the analysis of loss of heterozygosity in human cancers, and further studies using a larger panel of tumors may reveal an association between this polymorphism and specific types of cancer. C1 NCI,GENET LAB,BETHESDA,MD 20892. RP CHEDID, M (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Michieli, Paolo/A-2588-2011 NR 17 TC 102 Z9 106 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 3021 EP 3024 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200031 PM 8084608 ER PT J AU WONG, WT CARLOMAGNO, F DRUCK, T BARLETTA, C CROCE, CM HUEBNER, K KRAUS, MH DIFIORE, PP AF WONG, WT CARLOMAGNO, F DRUCK, T BARLETTA, C CROCE, CM HUEBNER, K KRAUS, MH DIFIORE, PP TI EVOLUTIONARY CONSERVATION OF THE EPS8 GENE AND ITS MAPPING TO HUMAN-CHROMOSOME 12Q23-Q24 SO ONCOGENE LA English DT Note ID RECEPTOR TYROSINE KINASES; SIGNALING PROTEINS; SH3 DOMAINS; IDENTIFICATION; PURIFICATION; SUBSTRATE; BINDS; CELLS AB We have previously isolated the coding sequence for a novel substrate for tyrosine kinases, eps8, from NIH3T3 fibroblasts. Eps8 was phosphorylated in vivo by several receptor tyrosine kinases (RTKs) and, upon overexpression, was able to enhance EGFR-mediated mitogenic signaling in NIH3T3 cells. To gain understanding of eps8 function as well as its role in normal and neoplastic proliferation, we cloned the human eps8 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. In addition to a previously identified SH3 domain, the predicted amino acid sequence of human eps8 revealed a non-random distribution of prolines, clustered in a way to suggest SH3-binding sites and a putative PH domain. Eps8 was expressed in all epithelial and fibroblastic lines examined and in some, but not all, hematopoietic cells. An essential function of eps8 in cell growth regulation was underscored by its conservation during evolution, where eps8-related sequences were detected as early as in Saccaromyces cerevisiae. Finally, the human EPS8 locus was mapped to chromosome 12q23-q24. C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. ATENEO FEDERICIANO, FAC MED & CHIRURG, DIPARTIMENTO BIOL & PATOL CELLULARE & MOLEC L CAL, NAPLES, ITALY. THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, JEFFERSON CANC INST, PHILADELPHIA, PA 19107 USA. REGINA ELENA INST CANC RES, MOLEC PATHOL & IMMUNOL LAB, ROME, ITALY. FAC MED & CHIRURG BARI, IST MICROBIOL, BARI, ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NCI NIH HHS [CA51083] NR 35 TC 25 Z9 27 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 3057 EP 3061 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200037 PM 8084614 ER PT J AU SEIDMAN, AD NORTON, L REICHMAN, BS CROWN, JPA YAO, TJ HAKES, TB LEBWOHL, DE GILEWSKI, TA HUDIS, CA SURBONE, A CURRIE, V KLECKER, R JAMISDOW, C COLLINS, J MARKS, L QUINLIVAN, S BERKERY, R CANETTA, R ONETTO, N ARBUCK, S AF SEIDMAN, AD NORTON, L REICHMAN, BS CROWN, JPA YAO, TJ HAKES, TB LEBWOHL, DE GILEWSKI, TA HUDIS, CA SURBONE, A CURRIE, V KLECKER, R JAMISDOW, C COLLINS, J MARKS, L QUINLIVAN, S BERKERY, R CANETTA, R ONETTO, N ARBUCK, S TI TAXOL (PACLITAXEL) PLUS RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN THE TREATMENT OF METASTATIC BREAST-CANCER SO ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on New Directions in Anti-Cancer Chemotherapy/4th International Congress on Anti-Cancer Chemotherapy CY 1993 CL PARIS, FRANCE DE TAXOL; PACLITAXEL; G-CSF; BREAST CANCER ID PHASE-I TRIAL; EVERY 21 DAYS; RESISTANCE; AGENT; DOXORUBICIN; MELANOMA; CELLS; DRUGS AB We treated 28 patients who had no prior chemotherapy for stage IV breast cancer and 51 patients with extensive prior exposure to other chemotherapeutic agents with a 24-hour infusion of Taxol (paclitaxel) as a single agent. Prophylactic recombinant human granulocyte colony-stimulating factor was administered routinely to ameliorate the anticipated dose-limiting toxicity of neutropenia. Nonhematologic toxicity was mild to moderate in most cases. Taxol was more active in patients with chemotherapy-naive stage IV disease, but activity was also observed in extensively treated patients as well. There is a strong clinical suggestion of at least partial noncross-resistance with doxorubicin. Taxol is a very promising agent for the treatment of metastatic breast cancer; its optimal application in this disease will be the subject of future trials. C1 US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,WALLINGFORD,CT 06492. NCI,DIV CANC TREATMENT,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP SEIDMAN, AD (reprint author), MEM SLOAN KETTERING CANC CTR,HOWARD BLDG,ROOM 1009,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-09207-14, 1-CM07311] NR 27 TC 1 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD OCT PY 1994 VL 51 SU 1 BP 33 EP 39 PG 7 WC Oncology SC Oncology GA PW311 UT WOS:A1994PW31100008 PM 7526308 ER PT J AU SHAARMA, R MARQUEZ, VE AF SHAARMA, R MARQUEZ, VE TI A CONCISE SYNTHESIS OF 8-PHENYLOCTADECANOIC ACID SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL LA English DT Note ID CHAIN RP MARQUEZ, VE (reprint author), NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ORGANIC PREP PROCEDURES INC PI NEWTON HIGHLANDS PA PO BOX 9, NEWTON HIGHLANDS, MA 02161 SN 0030-4948 J9 ORG PREP PROCED INT JI Org. Prep. Proced. Int. PD OCT PY 1994 VL 26 IS 5 BP 611 EP 614 PG 4 WC Chemistry, Organic SC Chemistry GA PM454 UT WOS:A1994PM45400022 ER PT J AU LENZ, FA GRACELY, RH HOPE, EJ BAKER, FH ROWLAND, LH DOUGHERTY, PM RICHARDSON, RT AF LENZ, FA GRACELY, RH HOPE, EJ BAKER, FH ROWLAND, LH DOUGHERTY, PM RICHARDSON, RT TI THE SENSATION OF ANGINA CAN BE EVOKED BY STIMULATION OF THE HUMAN THALAMUS SO PAIN LA English DT Article DE ANGINA PECTORIS; ELECTRICAL STIMULATION; NEURON; PAIN MEASUREMENT; VENTRAL POSTERIOR THALAMIC NUCLEUS; VISCERAL PAIN ID CORONARY-ARTERY OCCLUSION; CENTRAL NERVOUS-SYSTEM; INTRACARDIAC INJECTION; NEURONS; RESPONSES; PATHWAYS; NUCLEUS; MICROSTIMULATION; TERMINATIONS; BRADYKININ AB We have performed single-neuron recording and microstimulation in the region of the thalamic principal sensory nucleus (ventrocaudal nucleus, Vc) prior to implantation of a deep brain-stimulating electrode in a patient with pain secondary to arachnoiditis and with a past history of unstable angina. Cells located in the 16 mm lateral plane had cutaneous receptive fields on the chest wall. At and posterior to the location of these cells stimulation coincided precisely with the sensation of angina (stimulation-associated angina). The description of stimulation-associated angina was measured using a questionnaire and was identical to the patient's usual angina except that it began and terminated suddenly. Stimulation-associated angina was coincident with a tingling sensation in the leg. Clinical, hemodynamic, electrophysiologic and biochemical measures of cardiac function showed no evidence of myocardial strain or injury related to stimulation-associated angina. Since cells in the region of the principle sensory nucleus of thalamus respond to cardiac injury in animals, the present results suggest that this region mediates the sensation of angina. C1 JOHNS HOPKINS UNIV,DEPT NEUROSURG,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,DEPT CARDIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,DEPT OPHTHALMOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,ZANVYL KRIEGER MIND BRAIN INST,BALTIMORE,MD 21287. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 21287. OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [K08-NS1384, NS28598] NR 35 TC 51 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 1994 VL 59 IS 1 BP 119 EP 125 DI 10.1016/0304-3959(94)90055-8 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA PL956 UT WOS:A1994PL95600013 PM 7854792 ER PT J AU GRANT, DS KIBBEY, MC KINSELLA, JL CID, MC KLEINMAN, HK AF GRANT, DS KIBBEY, MC KINSELLA, JL CID, MC KLEINMAN, HK TI THE ROLE OF BASEMENT-MEMBRANE IN ANGIOGENESIS AND TUMOR-GROWTH SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE ECM; LAMININ; ANGIOGENESIS; TUMOR GROWTH; FGF; TNF; TAF ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; EXTRACELLULAR-MATRIX; LAMININ; INVITRO; DIFFERENTIATION; CANCER; INVIVO; IDENTIFICATION; BIOSYNTHESIS AB Expansion of the tumor-cell mass is dependent on both the degree of tumor vascularization and the rate of angiogenesis. Blood vessel growth is controlled, in part, by the matrix surrounding it, in particular the basement membrane underlying the endothelium. Here we illustrate that laminin, a major component of basement membrane, has several biologically active sites that can bind to endothelial and tumor cells, and have the ability to regulate angiogenesis and tumor growth. We show that synthetic peptides at two sites in the laminin B1 chain (the RGD and YIGSR sequences) inhibit angiogenesis, whereas a third site in the A chain, designated SIK-VAV, stimulates vessel and tumor cell growth. By developing strategies that promote or inhibit the activities of these sites in laminin, we may obtain methods to inhibit angiogenesis and subsequent tumor growth. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938 NR 53 TC 59 Z9 62 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PD OCT PY 1994 VL 190 IS 9-10 BP 854 EP 863 PG 10 WC Pathology SC Pathology GA PV311 UT WOS:A1994PV31100006 PM 7534913 ER PT J AU LE, DS THOMA, GR WECHSLER, H AF LE, DS THOMA, GR WECHSLER, H TI AUTOMATED PAGE ORIENTATION AND SKEW ANGLE DETECTION FOR BINARY DOCUMENT IMAGES SO PATTERN RECOGNITION LA English DT Article DE PAGE ORIENTATION; PROJECTION PROFILES; COMPONENT LABELING; HOUGH TRANSFORM; DOCUMENT SKEW ANGLE AB We describe the development and implementation of algorithms for detecting the page orientation (portrait/landscape) and the degree of skew for documents available as binary images. A new and fast approach is advanced herein whereby skew angle detection takes advantage of information found using the page orientation algorithm. Page orientation is accomplished using local analysis, while skew angle detection is implemented based on the processing of pixels of last black run-lengths of binary image objects. The experiments carried out on a variety of medical journals show the feasibility of the new approach and indicate that detection accuracy can be improved by minimizing the effects of non-textual data. C1 GEORGE MASON UNIV,DEPT COMP SCI,FAIRFAX,VA 22030. RP LE, DS (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20894, USA. NR 11 TC 86 Z9 90 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-3203 J9 PATTERN RECOGN JI Pattern Recognit. PD OCT PY 1994 VL 27 IS 10 BP 1325 EP 1344 DI 10.1016/0031-3203(94)90068-X PG 20 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA PL624 UT WOS:A1994PL62400004 ER PT J AU PIZZO, PA WILFERT, C AF PIZZO, PA WILFERT, C TI ANTIRETROVIRAL THERAPY FOR INFECTION DUE TO HUMAN-IMMUNODEFICIENCY-VIRUS IN CHILDREN SO PEDIATRIC AIDS AND HIV INFECTION-FETUS TO ADOLESCENT LA English DT Article AB Considerable progress has been made in developing treatment strategies that have improved the quality and duration of life of infants and children with symptomatic infection due to human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). To optimize these advances, antiretroviral therapy must be coupled with comprehensive, multidisciplinary supportive care and psychosocial support. It is also important to note that HIV infection in children differs from that in adults in terms of clinical presentation and rate of disease progression. The period of clinical latency is shorter, and disease progression can be accelerated in some infants and children.1-3 These characteristics of HIV disease in children provide measurable clinical end points that can be used to monitor progression of the disease and response to antiretroviral therapy. For example, the devastating impact of HIV infection on the linear growth, weight gain, and neurocognitive development of infants and children provides disease-specific measures for assessment of the activity and efficacy of antiretroviral agents. Similarly, the potential for immune recovery may be greater in young children; thus the magnitude of immune response to therapeutic interventions may be greater than that in HIV-infected adults. Drugs need to be administered to infants and children according to body weight or surface area, making careful pharmacokinetic monitoring necessary and permitting clinical-pharmacological correlations that can help validate the activity or toxicity of new antiretroviral agents.4-9 In this commentary we will review the current status of antiretroviral treatment of HIV-infected children and convey the current clinical standard of practice as well as areas of ongoing investigation, uncertainty, or controversy. RP PIZZO, PA (reprint author), NCI,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1045-5418 J9 PEDIATR AIDS HIV INF JI Pediatr. AIDS HIV Infect.-Fetus Adolesc. PD OCT PY 1994 VL 5 IS 5 BP 273 EP 295 PG 23 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA PV705 UT WOS:A1994PV70500001 PM 11361369 ER PT J AU WILFERT, CM PIZZO, PA AF WILFERT, CM PIZZO, PA TI A BLUEPRINT FOR CARE, TREATMENT, AND PREVENTION OF HIV/AIDS IN CHILDREN SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 1994 VL 13 IS 10 BP 920 EP 923 DI 10.1097/00006454-199410000-00013 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA PL948 UT WOS:A1994PL94800013 PM 7854893 ER PT J AU ABRAMS, SA SCHANLER, RJ YERGEY, AL VIEIRA, NE BRONNER, F AF ABRAMS, SA SCHANLER, RJ YERGEY, AL VIEIRA, NE BRONNER, F TI COMPARTMENTAL ANALYSIS OF CALCIUM-METABOLISM IN VERY-LOW-BIRTH-WEIGHT INFANTS SO PEDIATRIC RESEARCH LA English DT Article ID ENDOGENOUS FECAL EXCRETION; TERM INFANTS; DUAL-TRACER; HUMAN-MILK; ABSORPTION; KINETICS; FORMULA AB The calcium metabolism of 13 very-low-birth-weight infants fed a high-calcium diet was evaluated by means of stable isotope kinetic and balance studies. The studies used orally and i.v. administered stable isotopes, and the kinetic data were evaluated with the aid of a sequential, three-compartment model. The infants (postmenstrual age 33 +/- 1 wk, weight 1.34 +/- 0.03 kg) had higher bone calcium deposition rates (160 +/- 7 mg.kg(-1)d(-1) or 4.00 +/- 0.18 mmol.kg(-1)d(-1)) than those previously reported for either older children or adults. Furthermore, when analyzed as a function of net calcium absorption, bone calcium deposition rates increased markedly and significantly as net calcium absorption increased (r = 0.70, p < 0.01), whereas in older individuals, bone calcium deposition is a relatively invariant function of absorption. A relatively smaller response of bone calcium removal to calcium absorption was found for the very-low-birth-weight infants in this study (r = -0.39, p = 0.18), whereas in adults, bone calcium removal constitutes the major regulatory response. It is suggested that the calcium kinetic results in the very-low-birth-weight infants reflect the high rate of bone growth typical of the third trimester of gestation. C1 TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,DEPT BIOSTRUCT & FUNCT,FARMINGTON,CT 06030. RP ABRAMS, SA (reprint author), BAYLOR COLL MED,USDA ARS,CHILDRENS NUTR RES CTR,DEPT PEDIAT,110 BATES ST,HOUSTON,TX 77030, USA. OI Abrams, Steven/0000-0003-4972-9233 FU NCRR NIH HHS [M01-RR-01188] NR 36 TC 23 Z9 23 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1994 VL 36 IS 4 BP 424 EP 428 DI 10.1203/00006450-199410000-00002 PG 5 WC Pediatrics SC Pediatrics GA PH403 UT WOS:A1994PH40300002 PM 7816515 ER PT J AU GARTNER, LM CATZ, CS YAFFE, SJ AF GARTNER, LM CATZ, CS YAFFE, SJ TI NEONATAL BILIRUBIN WORKSHOP SO PEDIATRICS LA English DT Editorial Material C1 NICHHD,MOTHERS & CHILDRENS RES CTR,BETHESDA,MD 20892. RP GARTNER, LM (reprint author), UNIV CHICAGO,DEPT PEDIAT,CHICAGO,IL 60637, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1994 VL 94 IS 4 BP 537 EP 540 PN 1 PG 4 WC Pediatrics SC Pediatrics GA PK840 UT WOS:A1994PK84000025 PM 7936867 ER PT J AU BOYLE, WE BULL, MJ KATCHER, ML PALMER, SD RODGERS, GC SMITH, BL TULLY, SB AF BOYLE, WE BULL, MJ KATCHER, ML PALMER, SD RODGERS, GC SMITH, BL TULLY, SB TI OFFICE-BASED COUNSELING FOR INJURY PREVENTION SO PEDIATRICS LA English DT Editorial Material C1 AMBULATORY PEDIAT ASSOC,MCLEAN,VA. NICHHD,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. US DEPT TRANSPORTAT,WASHINGTON,DC 20590. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. US CONSUMER PROD SAFETY COMMISS,BETHESDA,MD 20816. RP BOYLE, WE (reprint author), MATERNAL & CHILD HLTH BUR,ROCKVILLE,MD, USA. NR 0 TC 37 Z9 37 U1 4 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1994 VL 94 IS 4 BP 566 EP 567 PN 1 PG 2 WC Pediatrics SC Pediatrics GA PK840 UT WOS:A1994PK84000033 ER PT J AU KAPLAN, MD TAYLOR, SE AMBUDKAR, IS AF KAPLAN, MD TAYLOR, SE AMBUDKAR, IS TI G-PROTEIN AND CAPACITATIVELY REGULATED CA2+ ENTRY PATHWAYS ARE ACTIVATED BY MUSCARINIC RECEPTOR STIMULATION IN A HUMAN SUBMANDIBULAR DUCTAL CELL-LINE SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CA2+ INFLUX; G-PROTEIN; MUSCARINIC RECEPTOR; CARBACHOL; THAPSIGARGIN; SALIVARY GLAND CELLS ID MEDIATED CALCIUM ENTRY; PAROTID ACINAR-CELLS; PLASMA-MEMBRANE; CA-2+ ENTRY; INFLUX; POOL; THAPSIGARGIN; MOBILIZATION; VOLUME; MN-2+ AB In the human submandibular ductal cell line (HSG) thapsigargin and carbachol stimulated Ca2+ re lease from the internal Ca2+ pool, resulting in the activation of capacitatively regulated Ca2+ entry (CRCE). This entry pathway was permeant to both Ca2+ and Mn2+, blocked by Ni2+ and insensitive to the muscarinic antagonist, atropine. Carbachol also stimulated an increase in cytosolic [Ca2+] in internal Ca2+-pool-depleted (i.e.thapsigargin-treated) cells which was dependent on the presence of external Ca2+ and blocked by Ni2+, demonstrating that it was due to Ca2+ entry. However, under the same experimental conditions, carbachol was unable to stimulate Mn2+ entry. Additionally, this latter carbachol-stimulated Ca2+ entry pathway was blocked by atropine. Pretreatment of HSG cells with AlF4-, increased basal rates of Mn2+ entry due to CRCE activation, but at tenuated carbachol-stimulated Ca2+ entry into thapsigargin-treated cells. The data suggest that two distinct divalent cation entry pathways are activated in muscarinic-receptor-stimulated HSG cells; a CRCE mechanism, permeable to both Mn2+ and Ca2+, and a second entry mechanism, permeable only to Ca2+. The latter does not depend on internal pool depletion, but appears to be regulated via G-protein activation. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. BAYLOR COLL DENT,DEPT ORAL SURG & PHARMACOL,DALLAS,TX 75246. NR 27 TC 21 Z9 21 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 1994 VL 428 IS 5-6 BP 439 EP 445 DI 10.1007/BF00374563 PG 7 WC Physiology SC Physiology GA PM919 UT WOS:A1994PM91900003 PM 7838665 ER PT J AU LI, J NIELSEN, S DAI, YS LAZOWSKI, KW CHRISTENSEN, EI TABAK, LA BAUM, BJ AF LI, J NIELSEN, S DAI, YS LAZOWSKI, KW CHRISTENSEN, EI TABAK, LA BAUM, BJ TI EXAMINATION OF RAT SALIVARY-GLANDS FOR THE PRESENCE OF THE AQUAPORIN CHIP SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AQP-CHIP; WATER CHANNEL; RAT SALIVARY GLANDS; MICROVASCULAR ENDOTHELIAL CELLS; CAPILLARY BED ID INTEGRAL MEMBRANE-PROTEIN; WATER-CHANNEL; FLUID SECRETION; EXPRESSION; KIDNEY; RECONSTITUTION; CDNA AB The aquaporin CHIP, AQP-CHIP, is a 28-kDa integral membrane protein that functions as a water channel in kidney and red blood cells. We have examined rat salivary glands for the presence of this molecule. In Northern blot analyses an AQP-CHIP cDNA hybrid ized to rat kidney mRNA approximately 20-fold more than to mRNA from the rat parotid gland. Western blot analyses, using antisera against human AQP-CHIP, showed that AQP-CHIP was present in crude membranes from rat salivary glands to a much lesser extent than in rat kidney membranes. A 2.8 kb cDNA encoding AQP-CHIP was also isolated from an adult rat parotid gland cDNA library. Immunolocalization studies using thin and ultrathin cryosections and light and electron microscopy, however, revealed that no glandular epithelium was labeled. In contrast, significant immunolabeling was present in microvascular endothelial cells. Non-fenestrated endothelia of capillaries and venules exhibited labeling on both their apical and basolateral membranes. The present study demonstrates that AQP-CHIP is not involved directly in fluid secretion from salivary epithelial cells. Further, this study provides strong evidence that AQP-CHIP is an endothelial cell water channel found within salivary gland tissue which may contribute to wa ter permeability in the capillary beds. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. UNIV ROCHESTER,DEPT DENT RES,ROCHESTER,NY 14642. UNIV ROCHESTER,DEPT BIOCHEM,ROCHESTER,NY 14642. NR 22 TC 49 Z9 54 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 1994 VL 428 IS 5-6 BP 455 EP 460 DI 10.1007/BF00374565 PG 6 WC Physiology SC Physiology GA PM919 UT WOS:A1994PM91900005 PM 7530838 ER PT J AU LANDI, MT BERTAZZI, PA SHIELDS, PG CLARK, G LUCIER, GW GARTE, SJ COSMA, G CAPORASO, NE AF LANDI, MT BERTAZZI, PA SHIELDS, PG CLARK, G LUCIER, GW GARTE, SJ COSMA, G CAPORASO, NE TI ASSOCIATION BETWEEN CYP1A1 GENOTYPE, MESSENGER-RNA EXPRESSION AND ENZYMATIC-ACTIVITY IN HUMANS SO PHARMACOGENETICS LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; SQUAMOUS-CELL CARCINOMA; LUNG-CANCER; CYTOCHROME-P450IA1 GENE; HUMAN-LYMPHOCYTES; SUSCEPTIBILITY; POLYMORPHISMS; POPULATION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; INDUCIBILITY AB Genetic susceptibility factors may play a role in determining adverse effects of exposure to environmental toxins. As a preliminary step to a molecular epidemiological study in a population exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), we investigated 20 healthy Caucasian volunteers with a set of putative susceptibility markers including a CYP1A1 Msp I restriction fragment length genetic polymorphism (RFLP), CYP1A1 mRNA expression, and ethoxyresorufin-O-deethylase (EROD) activity in cultured and mitogen-activated blood lymphocytes. Both basal (p = 0.008) and induced (P = 0.0001) EROD activity was significantly higher among persons with a mutation in one or both alleles of the CYP1A1 gene (variant CYP1A1 genotype). Induction in vitro by TCDD significantly increased EROD activity in both variant and wild-type CYP1A1 subjects; however, the absolute increase was greater in subjects with variant genotypes. An additive interaction between genotype and TCDD induction was suggested. Expression of CYP1A1 mRNA, both basal and induced, did not vary significantly across the genotypes. C1 UNIV MILAN,EPOCA,EPIDEMIOL RES CTR,I-20122 MILAN,ITALY. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. NYU,MED CTR,AJ LANZA RES LAB,TUXEDO PK,NY. RP LANDI, MT (reprint author), NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI Shields, Peter/I-1644-2012; bertazzi, pietro alberto/D-5039-2017 OI bertazzi, pietro alberto/0000-0003-3475-2449 NR 28 TC 185 Z9 195 U1 0 U2 6 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1994 VL 4 IS 5 BP 242 EP 246 DI 10.1097/00008571-199410000-00002 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA PQ676 UT WOS:A1994PQ67600002 PM 7894496 ER PT J AU MCKINNON, RA BURGESS, WM GONZALEZ, FJ GASSER, R MCMANUS, ME AF MCKINNON, RA BURGESS, WM GONZALEZ, FJ GASSER, R MCMANUS, ME TI SPECIES-SPECIFIC EXPRESSION OF CYP4B1 IN RABBIT AND HUMAN GASTROINTESTINAL TISSUES SO PHARMACOGENETICS LA English DT Article ID HUMAN-LIVER; CYTOCHROME-P-450 ISOZYME-5; DEPENDENT EXPRESSION; INSITU HYBRIDIZATION; MUTAGENIC PRODUCTS; MESSENGER-RNA; METABOLISM; LOCALIZATION; ACTIVATION; LUNG AB CYP4B1 is a P450 enzyme displaying tissue and species specific regulation. The rabbit CYP4B1 enzyme exhibits activity towards procarcinogenic aromatic amines. In the present study, CYP4B1 expression has been characterized in rabbit tissues using histological techniques, Northern blotting and Western blotting. Similar analyses were attempted using available human tissues. CYP4B1 mRNA and protein was demonstrated throughout the rabbit small intestine and colon. A unique 1.8 kb transcript, that is smaller than the transcript found in other tissues, was detected in rabbit stomach with a CYP4B1 specific RNA probe. No CYP4B1 protein was detected in this tissue. In rabbit liver, CYP4B1 was induced by phenobarbital primarily in zone 1 hepatocytes (periportal). In humans, CYP4B1 expression was demonstrated at low levels in human colon using in situ hybridization but not in liver or the small intestine. All rabbit gastrointestinal tissues other than stomach possess a high capacity for the activation of 2-aminofluorene compatible with CYP4B1 expression. In contrast, no activity was observed in human gastrointestinal microsomes. The present study therefore shows that CYP4B1 is an abundant P450 in the rabbit gastrointestinal tract and identifies species-specific differences in CYP4B1 expression and function. C1 UNIV QUEENSLAND,DEPT PHYSIOL & PHARMACOL,BRISBANE,QLD 4072,AUSTRALIA. FLINDERS UNIV S AUSTRALIA,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV BASEL,BIOCTR,DEPT PHARMACOL,CH-4056 BASEL,SWITZERLAND. RI McKinnon, Ross /B-9340-2009 OI McKinnon, Ross /0000-0002-3725-793X NR 30 TC 14 Z9 14 U1 0 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1994 VL 4 IS 5 BP 260 EP 270 DI 10.1097/00008571-199410000-00004 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA PQ676 UT WOS:A1994PQ67600004 PM 7894498 ER PT J AU CAPORASO, N WHITEHOUSE, J MONKMAN, S BOUSTEAD, C ISSAQ, H FOX, S MORSE, MA IDLE, JR CHUNG, FL AF CAPORASO, N WHITEHOUSE, J MONKMAN, S BOUSTEAD, C ISSAQ, H FOX, S MORSE, MA IDLE, JR CHUNG, FL TI IN-VITRO BUT NOT IN-VIVO INHIBITION OF CYP2D6 BY PHENETHYL ISOTHIOCYANATE (PEITC), A CONSTITUENT OF WATERCRESS SO PHARMACOGENETICS LA English DT Note ID LUNG-CANCER RISK; VITAMIN-A; POLYMORPHIC HYDROXYLATION; DEBRISOQUINE METABOLISM; EXTENSIVE METABOLIZERS; GENETIC PREDISPOSITION; QUINIDINE TREATMENT; BLADDER-CANCER; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; OXIDATION C1 AMER HLTH FDN,VALHALLA,NY 10595. UNIV NEWCASTLE UPON TYNE,NEWCASTLE TYNE NE1 7RU,TYNE & WEAR,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP CAPORASO, N (reprint author), NCI,GENET EPIDEMIOL BRANCH,EPN439,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. OI Idle, Jeff/0000-0002-6143-1520 FU NCI NIH HHS [CA 46535] NR 40 TC 13 Z9 14 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1994 VL 4 IS 5 BP 275 EP 280 DI 10.1097/00008571-199410000-00006 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA PQ676 UT WOS:A1994PQ67600006 PM 7894500 ER PT J AU ROTHMAN, RB PERT, A AF ROTHMAN, RB PERT, A TI EFFECTS OF ELECTROCONVULSIVE SHOCK ON THE RETENTION OF COCAINE-INDUCED CONDITIONING SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE COCAINE; CONDITIONING; LOCOMOTOR ACTIVITY; ELECTROCONVULSIVE SHOCK ID SENSITIZATION; AMPHETAMINE; DOPAMINE; MEMORY AB The purpose of these studies was to determine if ECS is capable of preventing the retention of cocaine-induced conditioned increases in locomotor behavior. One group of rats (paired) was injected with 40 mg/kg of cocaine immediately before a 30 min exposure to a locomotor monitoring chamber while the other group (unpaired) was injected with saline prior to a similar exposure. One hour following return to their home cages, the paired rats were injected with saline while the unpaired animals were injected with 40 mg/kg of cocaine. On day 2, both groups were injected with 10 mg/kg of cocaine and returned to the test apparatus. The presence of conditioned cocaine effects are indicated by enhanced locomotor output in the paired group relative to the unpaired group on day 2. ECS delivered immediately following training on day 1 was effective in preventing the retention of conditioning. ECS delivered 1 h prior to training, 1 h after or 1 h before on day 2 were ineffective. Cocaine-induced conditioning appears to involve associative learning that can be disrupted by ECS delivered immediately following training. C1 NIMH,BIOL PSYCHIAT BRANCH,ROCKVILLE,MD 20892. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NR 30 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 1994 VL 49 IS 2 BP 399 EP 404 DI 10.1016/0091-3057(94)90440-5 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PG355 UT WOS:A1994PG35500022 PM 7824556 ER PT J AU ALBRO, PW CORBETT, JT SCHROEDER, JL AF ALBRO, PW CORBETT, JT SCHROEDER, JL TI DOUBLY ALLYLIC HYDROPEROXIDE FORMED IN THE REACTION BETWEEN STEROL 5,7-DIENES AND SINGLET OXYGEN SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID METABOLISM AB Ergosterol and 7-dehydrocholesterol, common 5,7-conjugated diene sterols, react with photochemically produced singlet oxygen very efficiently to yield, in parallel pathways, the corresponding 5,8-endoperoxides and the 7 beta-hydroperoxy-5,8(9),22-trienol or -5,8(9)-dienol, respectively. The hydroperoxides decompose in an acid-catalyzed reaction to generate hydrogen peroxide and the 5,7,9(11),22-tetraenol or 5,7,9(11) trienol, respectively, with 1:1 stochiometry. The molar ratio of endoperoxide to hydroperoxide was constant (16:5) with two different reaction solvents, two different photosensitizers, and at all time points between 5 min and 3 h from the start of irradiation. Ergosterol did not react with either hydrogen peroxide or superoxide ion under our reaction conditions. Inhibition studies with nitrogen, 2,5-dimethylfuran, beta-carotene, and tert-butanol confirmed the involvement of singlet oxygen in these reactions. The unstable hydroperoxide would be expected to have undesirable biological consequences if formed in vivo. RP ALBRO, PW (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 28 Z9 29 U1 0 U2 3 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1994 VL 60 IS 4 BP 310 EP 315 DI 10.1111/j.1751-1097.1994.tb05109.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PL411 UT WOS:A1994PL41100003 PM 7991659 ER PT J AU SCHMITT, JM KNUTTEL, A YADLOWSKY, M ECKHAUS, MA AF SCHMITT, JM KNUTTEL, A YADLOWSKY, M ECKHAUS, MA TI OPTICAL-COHERENCE TOMOGRAPHY OF A DENSE TISSUE - STATISTICS OF ATTENUATION AND BACKSCATTERING SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BIOLOGICAL TISSUES; EYE-LENGTH; PERFORMANCE; INTERFEROMETRY; REFLECTOMETRY; ATMOSPHERE; TURBULENCE AB This paper addresses fundamental issues that underlie the interpretation of images acquired from turbid tissues by optical-coherence tomography (OCT). The attenuation and backscattering properties of freshly excised rat arteries and their dependence on the focusing and collection optics of the ocr system were measured at two wavelengths in the near infrared (830 nm and 1300 nm). Determined from the ratio of the magnitudes of the reflections from glass plates placed on both sides of the arteries, the mean attenuation coefficient of the arterial wall was found to be in the range 14 < mu(t) < 22 mm(-1) at 830 nm and 11 < mu(t) < 20 mm(-1) at 1300 nm. The measured values of mu(t) were lowest for the longer source wavelength and for probe beams with the smallest average diameters. The observed dependence of mu(t), on beam size indicates that relatively large-scale Variations in the index of refraction of the tissue contributed to degradation of the tranverse spatial coherence of the beam. We introduce a framework for understanding and quantifying beam-size effects by way of the mutual-coherence function. The fact that spatial variations in backscattering and attenuation (which includes spatial-coherence losses) have similar effects on OCT signals makes the origin of the signals difficult to determine. Evidence is given that suggests that, in spite of this difficulty, certain features of microstructures embedded several hundred micrometres deep in a turbid tissue can still be detected and characterized. C1 NHLBI,CELLULAR BIOL LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP SCHMITT, JM (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 19 TC 227 Z9 230 U1 2 U2 14 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT PY 1994 VL 39 IS 10 BP 1705 EP 1720 DI 10.1088/0031-9155/39/10/013 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA PK957 UT WOS:A1994PK95700013 PM 15551540 ER PT J AU MIYAZAWA, S JERNIGAN, RL AF MIYAZAWA, S JERNIGAN, RL TI PROTEIN STABILITY FOR SINGLE SUBSTITUTION MUTANTS AND THE EXTENT OF LOCAL COMPACTNESS IN THE DENATURED STATE SO PROTEIN ENGINEERING LA English DT Article DE HYDROPHOBIC ENERGY; INTER-RESIDUE CONTACT ENERGY; NATIVE-LIKE COMPACT DENATURED STATE; PROTEIN FOLDING; PROTEIN STABILITY ID SYNTHASE ALPHA-SUBUNIT; MOLTEN-GLOBULE STATE; AMINO-ACID-RESIDUES; T4 LYSOZYME; CONFORMATIONAL STABILITY; COOPERATIVE TRANSITIONS; STAPHYLOCOCCAL NUCLEASE; PACKING INTERACTIONS; FOLDED PROTEINS; UNIQUE POSITION AB The stability changes caused by single amino acid substitutions are studied by a simple, empirical method which takes account of the free energy change in the compact denatured state as well as in the native state. The conformational free energy is estimated from effective inter-residue contact energies, as evaluated in our previous study. When this method is applied, with a simple assumption about the compactness of the denatured state, for single amino acid replacements at Glu49 of the tryptophan synthase a subunit and at Ile3 of bacteriophage T4 lysozyme, the estimates of the unfolding Gibbs free energy changes correlate well with observed values, especially for hydrophobic amino acids, and it also yields the same magnitudes of energy as the observed values for both proteins. When it is also applied for amino acid replacements at various positions to estimate the average number of contacts at each position in the denatured state from the observed value of unfolding free energy change, those values for replacements with Gly and Ala at the same residue position in staphylococcal nuclease correlate well with each other. The estimated numbers of contacts indicate that the protein is not fully expanded in the denatured state and also that the compact denatured state may have a substantially native-like topology, like the molten globule state, in that there is a weak correlation between the estimated average number of contacts at each residue position in the denatured state and the number of contacts in the native structure. These results provide some further evidence that the inter-residue contact energies as applied here (i) properly reflect actual inter-residue interactions and (ii) can be considered to be a pairwise hydrophobicity scale. Also, the results indicate that characterization of the denatured state is critical to understanding the folding process. C1 NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,BETHESDA,MD 20892. RP MIYAZAWA, S (reprint author), GUNMA UNIV,FAC TECHNOL,KIRYU,GUMMA 376,JAPAN. RI Jernigan, Robert/A-5421-2012 NR 41 TC 54 Z9 54 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD OCT PY 1994 VL 7 IS 10 BP 1209 EP 1220 DI 10.1093/protein/7.10.1209 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PM113 UT WOS:A1994PM11300005 PM 7855136 ER PT J AU NORTH, ACT STEINERT, PM PARRY, DAD AF NORTH, ACT STEINERT, PM PARRY, DAD TI COILED-COIL STUTTER AND LINK SEGMENTS IN KERATIN AND OTHER INTERMEDIATE FILAMENT MOLECULES - A COMPUTER MODELING STUDY SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE COILED-COILS; KERATIN; INTERMEDIATE FILAMENT PROTEINS; LINK SEGMENTS; HEPTAD PHASING; COMPUTER MODELING ID AMINO-ACID-SEQUENCE; MOUSE EPIDERMAL KERATIN; II KERATINS; CROSS-LINKING; PROTEIN; DIVERSITY; VIMENTIN; TROPOMYOSIN; INFORMATION; HETERODIMER AB Structural discontinuities have previously been identified in four regions of the coiled-coil rod domain structure present in intermediate filament (IF) protein molecules. These include a point at which a phase shift occurs in the heptad periodicity characteristic of the sequence of polar and apolar residues in a-helical coiled-coils, and three links that lack a heptad substructure. We have studied these regions by computer-based molecular modeling and comparative sequence analysis and conclude that the phasing discontinuity can be accommodated without significant distortion of the overall double-helical chain conformation; the L2 Link has a similar conformation in all different types of IF molecules, a favorable conformation being one in which the two strands wrap tightly around each other; the L12 links vary in length between different IF types but contain important sequence similarities suggestive of a partial beta structure; the L1 links show larger variations in length, a lower degree of similarity, and probably diverse structures. Variations in the overall charges of the different links suggest that ionic interactions may play a significant role in filament assembly. The results also have general significance for other alpha-fibrous proteins in which either the characteristic heptad phasing undergoes a discontinuity or where a short non-coiled-coil sequence occurs within a coiled-coil rod domain structure. (C) 1994 Wiley-Liss, Inc. C1 MASSEY UNIV,DEPT PHYS & BIOPHYS,PALMERSTON NORTH,NEW ZEALAND. UNIV LEEDS,DEPT BIOCHEM & MOLEC BIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. NR 38 TC 37 Z9 38 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD OCT PY 1994 VL 20 IS 2 BP 174 EP 184 DI 10.1002/prot.340200207 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM792 UT WOS:A1994PM79200007 PM 7531336 ER PT J AU MATTHEWS, JH PATTABIRAMAN, N WARD, KB MANTILE, G MIELE, L MUKHERJEE, AB AF MATTHEWS, JH PATTABIRAMAN, N WARD, KB MANTILE, G MIELE, L MUKHERJEE, AB TI CRYSTALLIZATION AND CHARACTERIZATION OF THE RECOMBINANT HUMAN CLARA CELL 10-KDA PROTEIN SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE HUMAN CLARA CELL 10-KDA PROTEIN; X-RAY DIFFRACTION; PHOSPHOLIPASE A(2) INHIBITOR ID ANTIINFLAMMATORY PEPTIDES ANTIFLAMMINS; PLATELET-ACTIVATING-FACTOR; C2221 CRYSTAL FORM; PHOSPHOLIPASE-A2 ACTIVITY; PROGESTERONE-BINDING; OXIDIZED UTEROGLOBIN; RABBIT UTEROGLOBIN; KDA PROTEIN; EXPRESSION; RESOLUTION AB Crystals of recombinant human Clara cell 10-kDa protein were grown both from ammonium sulfate and polyethylene glycol (PEG) solutions. Crystals grown from ammonium sulfate solution have been characterized by X-ray diffraction studies as monoclinic with the space group C2 and lattice constants a = 69.2 Angstrom, b = 83.0 Angstrom, c = 58.3 Angstrom, and beta = 99.7 degrees. The monoclinic crystals diffract to beyond 2.5 Angstrom. Some of the crystals grown from PEG were of a similar habit to those grown from ammonium sulfate, but others were triclinic with the space group P1 and cell constants a = 40.3 Angstrom, b = 46.3 Angstrom, c = 51.3 Angstrom, alpha = 117.7 degrees, beta = 102.3 degrees, and gamma = 71.4 degrees. These crystals diffract to beyond 3.2 Angstrom. (C) 1994 Wiley-Liss, Inc.* C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. GEOCENTERS INC,FT WASHINGTON,MD 20744. MICHIGAN STATE UNIV,DEPT CHEM,E LANSING,MI 48824. NICHHD,HUMAN GENET BRANCH,GENET DEV SECT,BETHESDA,MD 20892. NR 51 TC 12 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 0887-3585 J9 PROTEINS JI Proteins PD OCT PY 1994 VL 20 IS 2 BP 191 EP 196 DI 10.1002/prot.340200209 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PM792 UT WOS:A1994PM79200009 PM 7846028 ER PT J AU POTTER, WZ MANJI, HK AF POTTER, WZ MANJI, HK TI REFRACTORY DEPRESSION - IS THERE A NEXT STEP SO PSYCHIATRIC ANNALS LA English DT Article ID BIPOLAR DISORDER RP POTTER, WZ (reprint author), NIMH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 2D-46,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 1994 VL 24 IS 10 BP 505 EP 507 PG 3 WC Psychiatry SC Psychiatry GA PP675 UT WOS:A1994PP67500001 ER PT J AU TIRELLI, E WITKIN, JM AF TIRELLI, E WITKIN, JM TI VERTICALIZATION OF BEHAVIOR ELICITED BY DOPAMINERGIC MOBILIZATION IS QUALITATIVELY DIFFERENT BETWEEN C57BL/6J AND DBA/2J MICE SO PSYCHOPHARMACOLOGY LA English DT Article DE APOMORPHINE; COCAINE; DOPAMINE RECEPTORS; CLIMBING BEHAVIOR; STEREOTYPED BEHAVIORS; DBA/2J MICE; C57BL/6J MICE ID INBRED MOUSE STRAINS; CLIMBING BEHAVIOR; LOCOMOTOR-ACTIVITY; EXPLORATORY-BEHAVIOR; GENETIC-CONTROL; APOMORPHINE; RECEPTORS; COCAINE; AGONISTS; BRAIN AB Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD. NR 52 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1994 VL 116 IS 2 BP 191 EP 200 DI 10.1007/BF02245062 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PM663 UT WOS:A1994PM66300010 PM 7862948 ER PT J AU MATHIS, C PAUL, SM CRAWLEY, JN AF MATHIS, C PAUL, SM CRAWLEY, JN TI THE NEUROSTEROID PREGNENOLONE SULFATE BLOCKS NMDA ANTAGONIST-INDUCED DEFICITS IN A PASSIVE-AVOIDANCE MEMORY TASK SO PSYCHOPHARMACOLOGY LA English DT Article DE NEUROSTEROID; MEMORY; AMNESIA; NMDA RECEPTOR; ATAXIA; RAT ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; GLUTAMYL-L-ASPARTATE; HIPPOCAMPAL-NEURONS; ANXIOLYTIC ACTIVITY; A RECEPTOR; RAT-BRAIN; STEROIDS; MICE; PROGESTERONE AB The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84-1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84-840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RI MATHIS, CHANTAL/B-6399-2013 NR 38 TC 107 Z9 108 U1 3 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1994 VL 116 IS 2 BP 201 EP 206 DI 10.1007/BF02245063 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PM663 UT WOS:A1994PM66300011 PM 7862949 ER PT J AU KOZIKOWSKI, AP MA, DW DU, LN LEWIN, NE BLUMBERG, PM AF KOZIKOWSKI, AP MA, DW DU, LN LEWIN, NE BLUMBERG, PM TI A PALLADIUM-CATALYZED ROUTE TO A BENZOFURAN ANALOG OF INDOLACTAM-V (ILV) - EFFECTS ON PKC ISOTYPE SELECTIVITY SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT 19th International Symposium on the Chemistry of Natural Products CY JAN 16-20, 1994 CL KARACHI, PAKISTAN SP INT UNION PURE & APPL CHEM, ORGANIC CHEM DIV, CHEM SOC PAKISTAN, H E J RES INST CHEM ID PROTEIN-KINASE-C; CELLS; ALPHA; EPSILON; OVEREXPRESSION; TRANSLOCATION; ACTIVATION; ISOENZYMES; ISOZYMES; GROWTH AB A novel palladium catalyzed synthesis of the benzofuran analogue 11 of n-hexyl-ILV and details of its isoform selectivity are described. Of considerable interest is the unexpected finding that this subtle structural change leads to a compound that is more like phorbol 12,13-dibutyrate (PDBu) and less like n-octyl-ILV in its pattern of activity. C1 NCI,BETHESDA,MD 20892. RP KOZIKOWSKI, AP (reprint author), MAYO FDN,4500 SAN PABLO RD,JACKSONVILLE,FL 32224, USA. NR 32 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD OCT-NOV PY 1994 VL 66 IS 10-11 BP 2087 EP 2090 DI 10.1351/pac199466102087 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA PM114 UT WOS:A1994PM11400027 ER PT J AU STRUDLER, PK AF STRUDLER, PK TI MOLECULAR STUDIES RELEVANT TO RADIATION ONCOLOGY - A RADIATION STUDY SECTION WORKSHOP SO RADIATION RESEARCH LA English DT Editorial Material ID PROTEIN-KINASE-C; IONIZING-RADIATION; DNA-REPAIR; HEME OXYGENASE; PLASMINOGEN-ACTIVATOR; GENETIC INSTABILITY; COLORECTAL-CANCER; MISMATCH REPAIR; MELANOMA-CELLS; EXPRESSION RP STRUDLER, PK (reprint author), NIH,DIV RES GRANTS,WESTWOOD BLDG 328,5333 WESTBARD AVE,BETHESDA,MD 20816, USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 1994 VL 140 IS 1 BP 143 EP 150 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA PK821 UT WOS:A1994PK82100020 ER PT J AU KULLIK, I STORZ, G AF KULLIK, I STORZ, G TI TRANSCRIPTIONAL REGULATORS OF THE OXIDATIVE STRESS-RESPONSE IN PROKARYOTES AND EUKARYOTES SO REDOX REPORT LA English DT Review ID NF-KAPPA-B; DNA-BINDING ACTIVITY; ESCHERICHIA-COLI K-12; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; SALMONELLA-TYPHIMURIUM; SUPEROXIDE-DISMUTASE; METALLOTHIONEIN GENE; POSITIVE REGULATOR; HYDROGEN-PEROXIDE AB Bacteria, yeast and cells of higher eukaryotes specifically induce the expression of genes encoding antioxidant defenses when exposed to reactive oxygen species, Recent studies have also suggested that reactive oxygen intermediates play a role as second messengers in signal transduction pathways, Therefore, cells must possess regulators that sense oxidant signals and transduce the signals into changes in gene expression, This review provides an overview of the transcription factors in Escherichia coli, Saccharomyces cerevisiae and mammalian cells that govern the response to oxidative stress, Some of the regulators function primarily as regulators of antioxidant genes while other regulators of the oxidative stress response also regulate genes important for metal homeostasis or cell metabolism during aerobic or anaerobic growth. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 62 TC 31 Z9 35 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 1351-0002 J9 REDOX REP JI Redox Rep. PD OCT PY 1994 VL 1 IS 1 BP 23 EP 29 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG310 UT WOS:A1994TG31000005 PM 27414173 ER PT J AU POLI, G KINTER, AL VICENZI, E FAUCI, AS AF POLI, G KINTER, AL VICENZI, E FAUCI, AS TI CYTOKINE REGULATION OF ACUTE AND CHRONIC HIV-INFECTION IN-VITRO - FROM CELL-LINES TO PRIMARY MONONUCLEAR-CELLS SO RESEARCH IN IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; DEFICIENCY SYNDROME AIDS; LONG TERMINAL REPEAT; FACTOR-ALPHA; NEF GENE; HTLV-III; EXPRESSION; REPLICATION C1 IST SCI SAN RAFFAELE,DIBIT,AIDS IMMUNOPATHOGENESIS UNIT,MILAN,ITALY. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. OI Vicenzi, Elisa/0000-0003-0051-3968 NR 37 TC 20 Z9 20 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 OCT-DEC PY 1994 VL 145 IS 8-9 BP 578 EP 582 DI 10.1016/S0923-2494(05)80036-7 PG 5 WC Immunology SC Immunology GA QG149 UT WOS:A1994QG14900002 PM 7754203 ER PT J AU GRAZIOSI, C PANTALEO, G FAUCI, AS AF GRAZIOSI, C PANTALEO, G FAUCI, AS TI COMPARATIVE-ANALYSIS OF CONSTITUTIVE CYTOKINE EXPRESSION IN PERIPHERAL-BLOOD AND LYMPH-NODES OF HIV-INFECTED INDIVIDUALS SO RESEARCH IN IMMUNOLOGY LA English DT Article ID T-CELL CLONES; TH1; PROFILES; SUBSETS; AIDS RP GRAZIOSI, C (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 15 TC 15 Z9 15 U1 0 U2 1 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 OCT-DEC PY 1994 VL 145 IS 8-9 BP 602 EP 607 DI 10.1016/S0923-2494(05)80040-9 PG 6 WC Immunology SC Immunology GA QG149 UT WOS:A1994QG14900007 PM 7754207 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI CELLULAR-IMMUNITY AND A TYPE-1 CYTOKINE PROFILE IN PROTECTION AGAINST HIV-INFECTION AND PROGRESSION TO AIDS SO RESEARCH IN IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; HOMOSEXUAL MEN; RESPONSES; INDIVIDUALS; ANTIGENS; PATTERNS; INTERLEUKIN-12; IMMUNIZATION; DYSFUNCTION; VACCINATION C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CLERICI, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. NR 49 TC 14 Z9 14 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 OCT-DEC PY 1994 VL 145 IS 8-9 BP 635 EP 643 DI 10.1016/S0923-2494(05)80046-X PG 9 WC Immunology SC Immunology GA QG149 UT WOS:A1994QG14900013 PM 7754213 ER PT J AU ADAMSON, PC AF ADAMSON, PC TI PHARMACOKINETICS OF ALL-TRANS-RETINOIC ACID - CLINICAL IMPLICATIONS IN ACUTE PROMYELOCYTIC LEUKEMIA SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT Investigators Meeting on Applications for Retinoids in Cancer Therapy CY DEC 03, 1993 CL ST LOUIS, MO SP TRICLINICA COMMUN, ROCHE LABS ID THERAPEUTIC ANTICANCER AGENTS; DIFFERENTIATION THERAPY; INVITRO METABOLISM; BINDING PROTEIN; PHARMACOLOGY; KETOCONAZOLE; EXPRESSION; REDUCTION; INDUCTION; HAMSTER RP ADAMSON, PC (reprint author), NCI,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 24 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1994 VL 31 IS 4 SU 5 BP 14 EP 17 PG 4 WC Hematology SC Hematology GA PM321 UT WOS:A1994PM32100002 PM 7831580 ER PT J AU BREITMAN, TR CHEN, ZX TAKAHASHI, N AF BREITMAN, TR CHEN, ZX TAKAHASHI, N TI POTENTIAL APPLICATIONS OF CYTODIFFERENTIATION THERAPY IN HEMATOLOGIC MALIGNANCIES SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT Investigators Meeting on Applications for Retinoids in Cancer Therapy CY DEC 03, 1993 CL ST LOUIS, MO SP TRICLINICA COMMUN, ROCHE LABS ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; BINDING-PROTEIN CRABP; BREAST-CANCER CELLS; SODIUM-BUTYRATE; GENE-EXPRESSION; HL-60 CELLS; MONOCYTIC DIFFERENTIATION; TERATOCARCINOMA CELLS; ADENOCARCINOMA CELLS RP BREITMAN, TR (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892, USA. NR 102 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1994 VL 31 IS 4 SU 5 BP 18 EP 25 PG 8 WC Hematology SC Hematology GA PM321 UT WOS:A1994PM32100003 PM 7831581 ER PT J AU OSHAUGHNESSY, JA FISHERMAN, JS COWAN, KH AF OSHAUGHNESSY, JA FISHERMAN, JS COWAN, KH TI COMBINATION PACLITAXEL (TAXOL) AND DOXORUBICIN THERAPY FOR METASTATIC BREAST-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID CELL-LINES C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 15 TC 31 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1994 VL 21 IS 5 SU 8 BP 19 EP 23 PG 5 WC Oncology SC Oncology GA PN383 UT WOS:A1994PN38300005 PM 7939757 ER PT J AU CARTER, HB PEARSON, JD AF CARTER, HB PEARSON, JD TI EVALUATION OF CHANGES IN PSA IN THE MANAGEMENT OF MEN WITH PROSTATE-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; TREATED PATIENTS; ANTIGEN; ADENOCARCINOMA; SERUM; DISEASE; HYPERPLASIA; DIAGNOSIS; MARKER; VOLUME C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP CARTER, HB (reprint author), JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,403 MARBURG,BALTIMORE,MD 21205, USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1994 VL 21 IS 5 BP 554 EP 559 PG 6 WC Oncology SC Oncology GA PM940 UT WOS:A1994PM94000006 PM 7524154 ER PT J AU EISENBERGER, MA CRAWFORD, ED WOLF, M BLUMENSTEIN, B MCLEOD, DG BENSON, R DORR, FA BENSON, M SPAULDING, JT AF EISENBERGER, MA CRAWFORD, ED WOLF, M BLUMENSTEIN, B MCLEOD, DG BENSON, R DORR, FA BENSON, M SPAULDING, JT TI PROGNOSTIC FACTORS IN STAGE D-2 PROSTATE-CANCER - IMPORTANT IMPLICATIONS FOR FUTURE TRIALS - RESULTS OF A COOPERATIVE INTERGROUP STUDY (INT.0036) SO SEMINARS IN ONCOLOGY LA English DT Article ID CARCINOMA C1 JOHNS HOPKINS UNIV,CTR ONCOL,DIV MED ONCOL,SW ONCOL GRP,BALTIMORE,MD 21287. UNIV COLORADO,DEPT SURG,DIV UROL,SW ONCOL GRP,DENVER,CO. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. SW ONCOL GRP,CTR STAT,SEATTLE,WA. WALTER REED ARMY MED CTR,DEPT SURG,UROL SERV,WASHINGTON,DC 20307. UNIFORMED UNIV HLTH SCI,UROL SERV,NATL PROSTATE CANC PROJECT,WASHINGTON,DC. MAYO CLIN & MAYO GRAD SCH MED,DEPT UROL,N CENT CANC TREATMENT GRP,ROCHESTER,MN 55901. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,BETHESDA,MD 20892. COLUMBIA UNIV,DEPT UROL,NATL PROSTAT CANC PROJECT,NEW YORK,NY. UNIV CALIF SAN FRANCISCO,DEPT UROL,NO CALIF ONCOL GRP,SAN FRANCISCO,CA 94143. RP EISENBERGER, MA (reprint author), JOHNS HOPKINS UNIV,CTR ONCOL,DIV MED ONCOL,MID ATLANTIC ONCOL PROGRAM,600 N WOLFE ST,BALTIMORE,MD 21287, USA. NR 23 TC 79 Z9 80 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1994 VL 21 IS 5 BP 613 EP 619 PG 7 WC Oncology SC Oncology GA PM940 UT WOS:A1994PM94000012 PM 7939752 ER PT J AU KOHNO, H GANDINI, O CURTIS, SW KORACH, KS AF KOHNO, H GANDINI, O CURTIS, SW KORACH, KS TI ANTIESTROGEN ACTIVITY IN THE YEAST TRANSCRIPTION SYSTEM - ESTROGEN-RECEPTOR MEDIATED AGONIST RESPONSE SO STEROIDS LA English DT Article DE ANTIESTROGEN; YEAST; ESTROGEN RECEPTOR; MOUSE; AGONIST ID PROGESTERONE RECEPTORS; STEROID-RECEPTORS; ACTIVATION; PHOSPHORYLATION; ANTIESTROGEN; EXPRESSION; SPECIFICITY; BINDING; INVIVO; REGION AB The mouse estrogen receptor was expressed in yeast cells to study the mechanism of action of anti-estrogens. Tamoxifen and hydroxytamoxifen, estrogen antagonists in mammalian tissues, failed to antagonize estradiol-induced expression of a VitA2-ERE-CTCl-lacZ reporter gene construct and exhibited full agonist activity, while nafoxidine exhibited partial antagonism as well as partial agonism. ICI 164,384 is a potent anti-estrogen in both mouse and human estrogen receptor systems. Our previous studies in the mouse ute, vs indicated that rapid degradation of the estrogen receptor accounted for the loss of estrogen responsiveness. In yeast however, ICI 164,384 or an isomer ICI 182,780 were unable to antagonize estradiol at concentration of 200 mu M. On the contrary, both ICI compounds exhibited partial agonist activity by stimulating beta-galactosinase activity to 50% that of estradiol. We examined the level of estrogen receptor in the yeast after treatment with estradiol, ICI 164,384 or vehicle by Western blot and found no ICI-induced reduction of estrogen receptor levels, but observed an increase in estrogen receptor following estradiol treatment. This indicates that the proteolytic activity responsible for degrading estrogen receptor in ICI 164,384-treated uteri or eukaryotic cells is not present in yeast. The agonist activity seen with ICI indicated that ICI-bound estrogen receptor is able to induce expression of an estrogen-responsive reporter gene. In support of this, estrogen receptor from ICI 164,384-treated yeast was able to bind an estrogen-responsive element in a gel-shift assay. The inability of ICI 164,384 to antagonize estradiol in the yeast gene-expression system will allow us to investigate mechanisms relevant to hormonal antagonism which are present in mammalian systems, but lacking in yeast. Agonistic activity of ICI 164,384 or ICI 182,780 and the lack of antagonism indicates that an active ICI receptor complex can be formed due to the deficient proteolysis in the yeast compared to mammalian systems where ICI stimulates increased receptor turnover and loss. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 30 TC 40 Z9 40 U1 0 U2 3 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD OCT PY 1994 VL 59 IS 10 BP 572 EP 578 DI 10.1016/0039-128X(94)90050-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PL637 UT WOS:A1994PL63700002 PM 7878684 ER PT J AU HORNE, MK MAYO, DJ ALEXANDER, HR STEINHAUS, EP CHANG, RC WHITMAN, E GRALNICK, HR AF HORNE, MK MAYO, DJ ALEXANDER, HR STEINHAUS, EP CHANG, RC WHITMAN, E GRALNICK, HR TI UPPER EXTREMITY IMPEDANCE PLETHYSMOGRAPHY IN PATIENTS WITH VENOUS ACCESS DEVICES SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID THROMBOSIS; CATHETER; TRIAL AB Central venous access devices (VADs) are often associated with thrombotic obstruction of the axillary-subclavian venous system. To explore the accuracy of impedance plethysmography (IPG) in identifying this complication we performed IPG on 35 adult cancer patients before their VADs were placed and approximately 6 weeks later. At the time of the second IPG the patients also underwent contrast venography of the axillary-subclavian system. The venograms revealed partial venous obstruction in 12 patients (34%) and complete obstruction in two (5.7%). Although the IPG results from venographically normal and abnormal patients overlapped extensively, mean measurements of venous outflow were significantly lower in the patient population with abnormal venograms (P = 0.052 for Vo; P = 0.0036 for Vo/Vc). In our hands, therefore, upper extremity IPG cannot be used to make clinical decisions about individual patients with VADs, but it can distinguish venographically normal and abnormal populations. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. RP HORNE, MK (reprint author), NCI,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,RM 2C390,BLDG 10,BETHESDA,MD 20892, USA. NR 6 TC 13 Z9 13 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 1994 VL 72 IS 4 BP 540 EP 542 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA PL563 UT WOS:A1994PL56300009 PM 7878628 ER PT J AU CONLON, MG FOLSOM, AR FINCH, A DAVIS, CE MARCUCCI, G SORLIE, P WU, KK AF CONLON, MG FOLSOM, AR FINCH, A DAVIS, CE MARCUCCI, G SORLIE, P WU, KK TI ANTITHROMBIN-III - ASSOCIATIONS WITH AGE, RACE, SEX AND CARDIOVASCULAR-DISEASE RISK-FACTORS SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID IMPROVED LIPOLYTIC EFFICIENCY; HEMOSTATIC VARIABLES; ENZYMATIC DETERMINATION; ORAL-CONTRACEPTIVES; DIABETES-MELLITUS; ARTERIAL-DISEASE; COAGULATION; PLASMA; WOMEN; FIBRINOLYSIS AB Antithrombin III (AT III) is a major inhibitor of blood coagulation, and hereditary deficiency is associated with venous thrombotic disease. The Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of 15,800 middle-aged men and women, measured AT III in its baseline examination. AT III levels were significantly higher in women than men, and in blacks than whites. AT III decreased with age in men but increased with age in women. In age- and race-adjusted analyses, ATIII was positively associated with smoking, HDL-cholesterol, triglycerides (men only), and in women, with diabetes and lipoprotein(a). AT III was negatively associated with educational level, body mass index in men, and use of female hormones in women. Most of these associations were confirmed in multivariate analysis. These correlations between AT III and other risk factors must be considered when evaluating AT III as a risk factor for venous or arterial thrombosis. C1 UNIV MINNESOTA,SCH PUBL HLTH,DEPT EPIDEMIOL,MINNEAPOLIS,MN 55454. UNIV TEXAS,SCH MED,DIV HEMATOL ONCOL,HOUSTON,TX. UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINATING,CHAPEL HILL,NC. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55015, N01-HC-55016] NR 50 TC 48 Z9 50 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 1994 VL 72 IS 4 BP 551 EP 556 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA PL563 UT WOS:A1994PL56300012 PM 7878631 ER PT J AU DAVIS, BJ MARONPOT, RR HEINDEL, JJ AF DAVIS, BJ MARONPOT, RR HEINDEL, JJ TI DI-(2-ETHYLHEXYL) PHTHALATE SUPPRESSES ESTRADIOL AND OVULATION IN CYCLING RATS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ESTROUS CYCLES; FOLLICLES; PLASTICIZER AB Di-(2-ethylhexyl) phthalate (DEHP) is a known reproductive toxicant and a carcinogen in rodent animal models. DEHP may also be a reproductive toxicant in women. Its action in female animal models is undetermined, although its potential to target the ovary has recently been shown. We have identified the ovarian toxicity and target cells of DEHP in the female rat. Adult, regularly cycling Sprague-Dawley rats were dosed daily with 2 g/kg DEHP in corn oil by gavage for 1 to 12 days. Ovarian morphology and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone levels were analyzed. DEHP exposure resulted in prolonged estrous cycles. Specifically. 35 of 42 DEHP-treated rats had 5- or 6-day cycles and only 7 of 42 had a 4-day cycle compared to 44 of 45 control rats with 4-day cycle lengths. DEHP treatment also suppressed or delayed ovulations by the first proestrus/estrus after metestrus-initiated dosing. Microscopic evaluation of the ovaries determined that 7 of 10 DEHP-exposed rats had not ovulated by vaginal estrus, whereas 13 of 13 control rats had ovulated by vaginal estrus. Thus, DEHP treatment significantly altered natural ovulation times. Preovulatory follicles were also quantitatively smaller in DEHP-exposed rats than in controls because the granulosa cells were smaller. The mean control rat preovulatory follicle granulosa cell area was 16 +/- 3 X 10(3) mu m, whereas the mean DEHP-treated rat preovulatory follicle granulosa cell area was 12 +/- 4 X 10(3) mu m. DEHP exposure significantly suppressed preovulatory follicle granulosa cell estradiol production over 8 days of exposure. Suppressed serum estradiol ler els caused secondary increases in FSH levels and did not stimulate the LH surge necessary for ovulation. Consequently, ovulation did not occur in DEHP-treated rats, although DEHP-treated rats ovulated after treatment with human chorionic hormone. Vaginal lavage cytology from rats treated with DEHP did not detect the ovarian toxicity as shown by histology and hormone analysis. In summary, exposure to DEHP resulted in hypoestrogenic anovulatory cycles and polycystic ovaries in adult female rats. (C) 1994 Academic Press, Inc. C1 NIEHS, EXPTL PATHOL LAB, RES TRIANGLE PK, NC 27709 USA. N CAROLINA STATE UNIV, COLL VET MED, DEPT MICROBIOL PATHOL & PARASITOL, RALEIGH, NC 27606 USA. RP NIEHS, DEV & REPRODUCT TOXICOL GRP, POB 12233, MDB3-06, RES TRIANGLE PK, NC 27709 USA. FU NIEHS NIH HHS [ES00233-02] NR 25 TC 212 Z9 238 U1 5 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1994 VL 128 IS 2 BP 216 EP 223 DI 10.1006/taap.1994.1200 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PP074 UT WOS:A1994PP07400006 PM 7940536 ER PT J AU DAVIS, BJ WEAVER, R GAINES, LJ HEINDEL, JJ AF DAVIS, BJ WEAVER, R GAINES, LJ HEINDEL, JJ TI MONO-(2-ETHYLHEXYL) PHTHALATE SUPPRESSES ESTRADIOL PRODUCTION INDEPENDENT OF FSH-CAMP STIMULATION IN RAT GRANULOSA-CELLS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID AROMATASE-ACTIVITY; HORMONE; CYTOCHROME-P-450; DIFFERENTIATION; LUTEINIZATION; INDUCTION; CULTURES; CLONING AB Di-(2-ethylhexyl) phthalate (DEHP) exposure suppressed preovulatory granulosa cell estradiol production in adult cycling rats. The active metabolite of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), suppressed follicle-stimulating hormone (FSH)-stimulated cAMP and progesterone production in cultured rat granulosa cells. To examine how DEHP altered granulosa cell estradiol production, the effects of MEHP were studied in cultures of rat granulosa cells. Granulosa cells were obtained from DES-implanted 25-day-old female Fisher 344 rats and exposed in culture to various concentrations of MEHP (0 to 400 mu m) in DMSO. Granulosa cells were stimulated with FSH, 8-bromo cyclic adenosine monophosphate (8br-cAMP), a stable cAMP analog, and various concentrations of testosterone. Estradiol production was measured by standard radioimmunoassays and normalized to cell protein. MEHP suppressed estradiol in a concentration-dependent manner whether granulosa cells were stimulated by FSH or 8-br cAMP. Therefore, MEHP suppressed estradiol independent of its suppression of the FSH-cAMP pathway and, thus, suppressed aromatase conversion of testosterone to estradiol. MEHP (100 mu m) decreased the maximum velocity of aromatase in cells supplied with increasing concentrations of testosterone. However, MEHP did not alter the velocity or affinity of microsomal aromatase isolated from adult virgin Sprague-Dawley rat ovaries. Therefore, MEHP altered the absolute amount or availability of aromatase in granulosa cells. Decreased aromatase in granulosa cells would explain decreased estradiol concentrations from DEHP exposure in vivo. (C) 1994 Academic Press, Inc. C1 N CAROLINA STATE UNIV,COLL VET MED,DEPT MICROBIOL PATHOL & PARASITOL,RALEIGH,NC 27606. RP DAVIS, BJ (reprint author), NIEHS,REPROD & DEV TOXICOL GRP,POB 12233,MDB3-06,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [ES00233-02] NR 16 TC 85 Z9 91 U1 2 U2 11 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1994 VL 128 IS 2 BP 224 EP 228 DI 10.1006/taap.1994.1201 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PP074 UT WOS:A1994PP07400007 PM 7940537 ER PT J AU LUSTER, MI PORTIER, C PAIT, DG GERMOLEC, DR AF LUSTER, MI PORTIER, C PAIT, DG GERMOLEC, DR TI THE USE OF ANIMAL TESTS IN RISK ASSESSMENT FOR IMMUNOTOXICOLOGY SO TOXICOLOGY IN VITRO LA English DT Article; Proceedings Paper CT 4th CFN Symposium on Immunotoxicology and In Vitro Possibilities CY SEP 19-21, 1993 CL STOCKHOLM, SWEDEN SP NATL BOARD LAB ANIM ID GUIDELINES; IMMUNE AB The design and content of a screening battery using a 'tier' approach for detecting potential immunotoxic compounds in mice has been described (M. I. Luster et al., Fundamental and Applied Toxicology 1988, 10, 2-19). The database generated from these studies, which consists of over 50 selected compounds, has been analysed in an attempt to improve future testing strategies and provide information to aid in developing future quantitative risk assessment for immunotoxicity. In a recent study if was shown that as few as two or three immune parameters were needed to predict immunotoxicants in mice (M. I. Luster et al., Fundamental and Applied Toxicology 1992, 18, 200-210). The analyses described here focus on the use of this database to develop statistical models that examine the qualitative and quantitative relationship(s) between the immune function and host resistance tests. The conclusions derived from these analyses are as follows: (1) A good correlation exists between changes in the immune tests and altered host resistance, in that there were no instances where host resistance was altered without affecting one or more immune test(s). However, in some instances immune changes occurred without corresponding changes in host resistance. (2) No single immune test could be identified that was fully predictive for altered host resistance, although most assays were relatively good indicators (i.e. >70%). Several others, such as proliferative response to lipopolysaccharide and leucocyte counts, were found to be relatively poor indicators for host resistance changes. (3) The ability to resist infectious agent challenge is dependent on the degrees of immunosuppression and the quantity of infectious agent administered. (4) Logistic and standard regression modelling using one extensive chemical data set from the immunosuppressive agent, cyclophosphamide, indicated that most immune function-host resistance relationships followed linear rather than linear-quadratic (threshold-like) models. For most of the relationships this could not be confirmed using a large chemical data set and, thus, a more mechanistically based approach for modelling will need to be developed. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP LUSTER, MI (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 11 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD OCT PY 1994 VL 8 IS 5 BP 945 EP 950 DI 10.1016/0887-2333(94)90224-0 PG 6 WC Toxicology SC Toxicology GA PN579 UT WOS:A1994PN57900005 PM 20693051 ER PT J AU SUNDWALL, A ANDERSSON, B BALLS, M DEAN, J DESCOTES, J HAMMARSTROM, S HULTMAN, P KIMBER, I LORENTZ, M LUSTER, M MOLDEUS, P ODLAND, L SJOGREN, HO STEJSKAL, V WALUM, E VERONESI, B WHITE, K VOS, J AF SUNDWALL, A ANDERSSON, B BALLS, M DEAN, J DESCOTES, J HAMMARSTROM, S HULTMAN, P KIMBER, I LORENTZ, M LUSTER, M MOLDEUS, P ODLAND, L SJOGREN, HO STEJSKAL, V WALUM, E VERONESI, B WHITE, K VOS, J TI WORKSHOP - IMMUNOTOXICOLOGY AND IN-VITRO POSSIBILITIES SO TOXICOLOGY IN VITRO LA English DT Article; Proceedings Paper CT 4th CFN Symposium on Immunotoxicology and In Vitro Possibilities CY SEP 19-21, 1993 CL STOCKHOLM, SWEDEN SP NATL BOARD LAB ANIM C1 CALAB,MED LABS,S-10055 STOCKHOLM,SWEDEN. ECVAM,INST ENVIRONM,JOINT RES CTR,I-21020 ISPRA,ITALY. STERLING WINTHROP INC,DRUG DEV & SAFETY ASSESSMENT,COLLEGEVILLE,PA 19426. FAC MED ALEXIS CARREL,INSERM,U80,IMMUNOTOXICOL FONDAMENTALE & CLIN LAB,F-69008 LYON,FRANCE. UMEA UNIV,DEPT IMMUNOL,S-90187 UMEA,SWEDEN. LINKOPING UNIV HOSP,DEPT PATHOL 1,S-58185 LINKOPING,SWEDEN. ZENECA CENT TOXICOL LAB,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. MINIST AGR,CFN,S-10333 STOCKHOLM,SWEDEN. NIEHS,RES TRIANGLE PK,NC 27709. ASTRA RES CTR AB,SAFETY ASSESSMENT,S-15185 SODERTALJE,SWEDEN. LUND UNIV,DEPT TUMORIMMUNOL,WALLENBERG LAB,S-22007 LUND,SWEDEN. UNIV STOCKHOLM,DEPT NEUROCHEM & NEUROTOXICOL,S-10691 STOCKHOLM,SWEDEN. US EPA,DIV CELLULAR & MOLEC TOXICOL NEUROTOXICOL,RES TRIANGLE PK,NC 27711. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOMED ENGN,RICHMOND,VA 23298. NATL INST PUBL HLTH & ENVIRONM PROTECT,3720 BA BILTHOVEN,NETHERLANDS. RP SUNDWALL, A (reprint author), PHARMACIA AB,TOXICOL & SAFETY ASSESSMENT,BIOCHEM TOXICOL UNIT,BOX 941,S-25109 HELSINGBORG,SWEDEN. NR 0 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD OCT PY 1994 VL 8 IS 5 BP 1067 EP 1074 DI 10.1016/0887-2333(94)90246-1 PG 8 WC Toxicology SC Toxicology GA PN579 UT WOS:A1994PN57900027 PM 20693073 ER PT J AU DAVEY, RJ HEATON, WAL SWEAT, LT STEC, NM NELSON, EJ HOLME, S AF DAVEY, RJ HEATON, WAL SWEAT, LT STEC, NM NELSON, EJ HOLME, S TI CHARACTERISTICS OF WHITE CELL-REDUCED RED-CELLS STORED IN TRI-(2-ETHYLHEXYL)TRIMELLITATE PLASTIC SO TRANSFUSION LA English DT Article ID DI-(2-ETHYLHEXYL) PHTHALATE; WHOLE-BLOOD; STORAGE; SURVIVAL; LEUKOCYTE; CONTAINER; BAGS; DEHP AB Background: Standard blood storage containers contain extractable plasticizers that accumulate in blood during storage and are an unintended transfusion product. However, extractable plasticizers have a protective effect on the red cell membrane and improve red cell storage variables. Prestorage white cell reduction also improves selected red cell storage variables. Study Design and Methods: The study evaluated whether the beneficial effect of prestorage white cell reduction would offset the negative effect of the absence of extractable plasticizer in red cells stored in AS-3 for 42 days at 4 degrees C. Filtered red cells stored in polyvinylchroride containers with the nonextracting plasticizer, tri-(2-ethylhexyl)trimellitate (TEHTM), were compared to unfiltered red cells stored in polyvinylchloride containers with the extractable plasticizer di-(2-ethylhexyl)phthalate (DEHP). Results: Poststorage supernatant potassium and red cell osmotic fragility were significantly higher in white cell-reduced TEHTM units than in unfiltered DEHP units. The mean 24-hour recovery of the filtered TEHTM red cells was significantly lower than that of the unfiltered DEHP red cells (69.1 +/- 7.4% vs. 77.1 +/- 5.1%, p<0.05, n = 8). Conclusion: These data demonstrate that white cell reduction before 42-day storage in TEHTM containers with currently approved preservatives does not yield an acceptable red cell component. C1 MILES INC,COVINA,CA. AMER RED CROSS,NORFOLK,VA. RP DAVEY, RJ (reprint author), NIH,DEPT TRANSFUS MED,LAB SERV SECT,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 24 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1994 VL 34 IS 10 BP 895 EP 898 DI 10.1046/j.1537-2995.1994.341095026977.x PG 4 WC Hematology SC Hematology GA PL444 UT WOS:A1994PL44400012 PM 7940663 ER PT J AU BOWMAN, C COTTLERFOX, M AF BOWMAN, C COTTLERFOX, M TI STANDARDIZING FLOW-CYTOMETRY OF CD34+ HEMATOPOIETIC STEM-CELLS USING FROZEN CELL-LINES SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 34 IS 10 SU S BP S58 EP S58 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900229 ER PT J AU CONRYCANTILENA, C KLEIN, HG DHARIWAL, K YU, R LEVINE, MA AF CONRYCANTILENA, C KLEIN, HG DHARIWAL, K YU, R LEVINE, MA TI ASCORBIC-ACID CONCENTRATION AND ACCUMULATION IN APHERESIS PLATELETS OVER 5-DAY STORAGE SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 34 IS 10 SU S BP S16 EP S16 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900063 ER PT J AU DAVEY, RJ PROCTER, JL BROWN, KE AF DAVEY, RJ PROCTER, JL BROWN, KE TI SCREENING FOR P-ANTIGEN NEGATIVE RED-CELLS USING PARVOVIRUS B19 CAPSIDS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 34 IS 10 SU S BP S70 EP S70 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900279 ER PT J AU FITZGERALD, M BUTZ, RE PROCTER, JL DAVEY, RJ AF FITZGERALD, M BUTZ, RE PROCTER, JL DAVEY, RJ TI ADSORPTION OF WARM-REACTIVE RBC AUTOANTIBODIES USING FORMALIN-FIXED PLATELETS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 34 IS 10 SU S BP S78 EP S78 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900310 ER PT J AU KORELITZ, JJ BUSCH, MP KLEINMAN, SH WILLIAMS, AE ZUCK, TF GILCHER, RO CHIEN, HC AF KORELITZ, JJ BUSCH, MP KLEINMAN, SH WILLIAMS, AE ZUCK, TF GILCHER, RO CHIEN, HC TI ABILITY OF ANTI-HBC TO DETECT RETROVIRUS SEROPOSITIVE BLOOD-DONORS SO TRANSFUSION LA English DT Meeting Abstract C1 NHLBI,RETROPVIRUS EPIDEMIOL DONOR STUDY,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 34 IS 10 SU S BP S37 EP S37 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900146 ER PT J AU LEE, JH LEITMAN, SF AF LEE, JH LEITMAN, SF TI A CONTROLLED-STUDY OF THE EFFICACY OF HETASTARCH AND PENTASTARCH IN GRANULOCYTE COLLECTIONS BY CENTRIFUGAL LEUKAPHERESIS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1994 VL 34 IS 10 SU S BP S59 EP S59 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900234 ER PT J AU LEE, JH KLEIN, HG AF LEE, JH KLEIN, HG TI THE EFFECT OF THE DONOR ERYTHROCYTE SEDIMENTATION-RATE ON THE EFFICIENCY OF GRANULOCYTE COLLECTION BY CENTRIFUGAL LEUKAPHERESIS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1994 VL 34 IS 10 SU S BP S3 EP S3 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900012 ER PT J AU LEITMAN, SF YU, M LEKSTROM, J MALECH, HL GALLIN, JI AF LEITMAN, SF YU, M LEKSTROM, J MALECH, HL GALLIN, JI TI CONTROLLED TRIAL OF RECOMBINANT GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) IN HEALTHY LEUKAPHERESIS DONORS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 34 IS 10 SU S BP S5 EP S5 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900019 ER PT J AU STRONCEK, DF LEONARD, K GALLIN, JI MALECH, HL LEITMAN, SF AF STRONCEK, DF LEONARD, K GALLIN, JI MALECH, HL LEITMAN, SF TI ALLOIMMUNIZATION FOLLOWING GRANULOCYTE TRANSFUSIONS SO TRANSFUSION LA English DT Meeting Abstract C1 UNIV MINNESOTA, MINNEAPOLIS, MN USA. NIAID, DEPT TRANSFUS MED, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD OCT PY 1994 VL 34 IS 10 SU S BP S77 EP S77 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900304 ER PT J AU HINNEBUSCH, AG AF HINNEBUSCH, AG TI TRANSLATIONAL CONTROL OF GCN4 - AN IN-VIVO BAROMETER OF INITIATION-FACTOR ACTIVITY SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID NUCLEOTIDE-EXCHANGE FACTOR; PROTEIN-KINASE GCN2; TRANSFER-RNA-SYNTHETASES; OPEN READING FRAMES; SACCHAROMYCES-CEREVISIAE; FACTOR-II; MESSENGER-RNA; ALPHA-SUBUNIT; YEAST; ACTIVATOR AB Phosphorylation of translation initiation factor-2 (elF-2) is an adaptive mechanism for downregulating protein synthesis under conditions of starvation and stress. The yeast Saccharomyces has evolved a sophisticated means of increasing translation of GCN4 mRNA when elF-2 is phosphorylated, allowing the induction of an important stress-response protein when expression of most other genes is decreasing. Because translation of GCN4 mRNA is so tightly coupled to elF-2 activity, genetic analysis of this system has provided unexpected insights into the regulation of elF-2 and its guanine nucleotide exchange factor, elF-2B. RP HINNEBUSCH, AG (reprint author), NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892, USA. NR 36 TC 154 Z9 155 U1 0 U2 4 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 OCT PY 1994 VL 19 IS 10 BP 409 EP 414 DI 10.1016/0968-0004(94)90089-2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP019 UT WOS:A1994PP01900008 PM 7817398 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - BETTER COMPETENT CELLS AND DNA-POLYMERASE CONTAMINANTS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ESCHERICHIA-COLI; TRANSFORMATION; PLASMIDS RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD OCT PY 1994 VL 19 IS 10 BP 426 EP 427 DI 10.1016/0968-0004(94)90092-2 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP019 UT WOS:A1994PP01900011 PM 7817400 ER PT J AU MOODY, EJ HARRIS, BD SKOLNICK, P AF MOODY, EJ HARRIS, BD SKOLNICK, P TI THE POTENTIAL FOR SAFER ANESTHESIA USING STEREOSELECTIVE ANESTHETICS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID CHLORIDE CHANNEL COMPLEX; A RECEPTOR COMPLEX; BENZODIAZEPINE RECEPTOR; INHALATIONAL ANESTHETICS; NEUROCHEMICAL ACTIONS; VOLATILE ANESTHETICS; GENERAL-ANESTHETICS; XENOPUS OOCYTES; BINDING; HALOTHANE AB The molecular mechanisms by which inhalational agents produce anaesthesia remains a subject of controversy, despite a history of clinical use spanning two centuries. The demonstration of a significant difference in the anaesthetic potencies of (+)- and (-)-isoflurane provides compelling evidence for the hypothesis that proteins, rather than lipids, are the primary sites of anaesthetic action. Moreover, the optically active isomers of volatile anaesthetics provide new tools to discriminate among putative molecular targets of anaesthesia. A difference in the anaesthetic potencies of (+)- and (-)-isoflurane, together with an apparent lack of stereoselectivity in their myocardial suppression, raises the possibility that an optically active volatile agent may have clinical advantages over currently available racemic mixtures and is discussed in this article by Eric Moody, Bradford Harris and Phil Skolnick. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. RP MOODY, EJ (reprint author), JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287, USA. NR 44 TC 25 Z9 25 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 OCT PY 1994 VL 15 IS 10 BP 387 EP 391 DI 10.1016/0165-6147(94)90160-0 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ155 UT WOS:A1994PQ15500008 PM 7809955 ER PT J AU LEES, A FINKELMAN, F INMAN, JK WITHERSPOON, K JOHNSON, P KENNEDY, J MOND, JJ AF LEES, A FINKELMAN, F INMAN, JK WITHERSPOON, K JOHNSON, P KENNEDY, J MOND, JJ TI ENHANCED IMMUNOGENICITY OF PROTEIN-DEXTRAN CONJUGATES .1. RAPID STIMULATION OF ENHANCED ANTIBODY-RESPONSES TO POORLY IMMUNOGENIC MOLECULES SO VACCINE LA English DT Article DE PROTEIN-DEXTRAN CONJUGATES; IMMUNOGENICITY; ENHANCED RESPONSE ID THYMUS-INDEPENDENT ANTIGENS; INFLUENZAE TYPE-B; ACTIVATION; CELLS; POLYSACCHARIDE; REQUIREMENTS; COMPLEX; FICOLL; BEADS; MICE AB In view of our observation that anti-immunoglobulin antibody conjugated to high-molecular-weight dextran stimulates high levels of B-cell activation (Brunswick et al. J. Immunol. 1989, 143, 1239), we coupled T cell-dependent antigens to dextran. When mice were immunized, in the absence of adjuvant, with a BSA-dextran conjugate (BSA-dex), a persistent, high-titre anti-BSA IgG1 response was induced. Titres were dose-dependent and seen with as little as 10 mu g of conjugated protein. Anti-BSA titres were detected as early as day 7, usually peaked at about day 14 and persisted for at least 4 weeks. Anti-hapten antibodies were also elicited in mice that were immunized with haptenated BSA covalently bound to dextran, and secondary responses could be induced even after inoculation of the unconjugated protein. Covalent attachment of the protein to the polymer was necessary, and the response was specific, as coinjection of BSA-dex and an unrelated antigen, goat IgG, did not elicit detectable anti-goat antibodies. The immunogenic potential of these conjugates did not depend on the ability of the dextran carrier to induce antibody, inasmuch as they stimulated high levels of anti-protein antibody in mice unresponsive to dextran. A minimum size dextran polymer was required for 2000 kDa but not of 70 kDa gave detectable anti-BSA titres. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP LEES, A (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MED,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. FU NIAID NIH HHS [R01 AI21328, R01 AI24273, R01 AI27465] NR 34 TC 23 Z9 24 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD OCT PY 1994 VL 12 IS 13 BP 1160 EP 1166 DI 10.1016/0264-410X(94)90237-2 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PG671 UT WOS:A1994PG67100002 PM 7530886 ER PT J AU JURRIAANS, S VANGEMEN, B WEVERLING, GJ VANSTRIJP, D NARA, P COUTINHO, R KOOT, M SCHUITEMAKER, H GOUDSMIT, J AF JURRIAANS, S VANGEMEN, B WEVERLING, GJ VANSTRIJP, D NARA, P COUTINHO, R KOOT, M SCHUITEMAKER, H GOUDSMIT, J TI THE NATURAL-HISTORY OF HIV-1 INFECTION - VIRUS LOAD AND VIRUS PHENOTYPE INDEPENDENT DETERMINANTS OF CLINICAL COURSE SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; MONONUCLEAR-CELLS; SEROPOSITIVE INDIVIDUALS; TYPE-1 INFECTION; VIRAL BURDEN; AIDS; PLASMA; RNA; EXPRESSION AB Virus load and Virus phenotype have both been indicated as major determinants of disease progression in HIV-I infection. In this study HIV-1 RNA copy numbers in serum, virus phenotype, and CD4+ cell counts were analyzed longitudinally in a group of 20 seroconverters progressing to AIDS within 5.5 years. In this group 12 individuals developed AIDS without syncytium-inducing (SI) viruses ever being isolated, while 8 individuals showed a non-SI (NSI) to SI phenotypic switch prior to AIDS development. HIV-1 RNA copy numbers in sera of all progressors were stable and high from seroconversion until development of AIDS. Twenty-one seroconverters remaining asymptomatic for more than 5.5 years were selected as nonprogressing controls, and both progressors and nonprogressors were evaluated at seroconversion and early in infection (3 years post seroconversion). Comparative analysis revealed that at the point of seroconversion HIV-I RNA copy numbers in sera from NSI progressors, SI progressors, and nonprogressors were not significantly different, nor were their CD4+ cell counts. At seroconversion all individuals harbored viruses with an NSI phenotype. In contrast to the progressors, HIV-1 RNA copy numbers in sera of nonprogressors had declined significantly during the early period of infection. At the second time point RNA copy numbers in the sera of NSI progressors and nonprogressors differed significantly (P = 0.0005), while RNA copy numbers in the sera of SI progressors and nonprogressors did not. However, at this time point the CD4+ cell counts of SI progressors were significantly lower than those from nonprogressors (P = 0.002), while the CD4+ cell counts of NSI progressors and nonprogressors did not differ significantly These results show that early in HIV-I infection progressors and nonprogressors are distinguishable. NSI progressors can be distinguished from nonprogressors on the basis of serum HIV-1 RNA load and SI progressors on the basis of CD4+ cell decline. In addition, a significant decrease in the number of HIV-I RNA copies in the early phase of infection seems to postpone the development of AIDS. (C) 1994 Academic Press, Inc. C1 ORGANON TEKNIKA NV,5281 RM BOXTEL,NETHERLANDS. UNIV AMSTERDAM,ACAD MED CTR,DEPT CLIN EPIDEMIOL & BIOSTAT,1105 AZ AMSTERDAM,NETHERLANDS. NCI,TUMOR CELL BIOL LAB,VIRUS BIOL SECT,FREDERICK,MD 21701. DEPT PUBL HLTH & ENVIRONM,MUNICIPAL HLTH SERV,1018 WT AMSTERDAM,NETHERLANDS. NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,DEPT CLIN VIROIMMUNOL,1066 CX AMSTERDAM,NETHERLANDS. RP JURRIAANS, S (reprint author), UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,MEIBERGDREEF 15,1105 AZ AMSTERDAM,NETHERLANDS. NR 39 TC 173 Z9 174 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 1994 VL 204 IS 1 BP 223 EP 233 DI 10.1006/viro.1994.1526 PG 11 WC Virology SC Virology GA PG067 UT WOS:A1994PG06700023 PM 7916514 ER PT J AU BATTAINI, F PASCALE, A LUCCHI, L RACCHI, M BERGAMASCHI, S PARENTI, M WETSEL, WC GOVONI, S TRABUCCHI, M AF BATTAINI, F PASCALE, A LUCCHI, L RACCHI, M BERGAMASCHI, S PARENTI, M WETSEL, WC GOVONI, S TRABUCCHI, M TI EXPRESSION AND REGULATION OF CALCIUM-INDEPENDENT PROTEIN-KINASE-C IN NG-108-15 CELL-DIFFERENTIATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHORBOL ESTER BINDING; NEURO-BLASTOMA CELLS; RAT-BRAIN; NEUROBLASTOMA-CELLS; SIGNAL TRANSDUCTION; EPSILON-ISOFORM; DOWN-REGULATION; MESSENGER-RNAS; HYBRID-CELLS; PKC-ALPHA AB Protein, mRNA and activity levels of the calcium-independent protein kinase C (nPKC) isoenzymes were examined in NG108-15 cells. Western blot analyses reveal that proliferating NG 108-15 cells express the delta, epsilon and eta, but not the theta species. The atypical specie PKC zeta was also detected. Differentiation of these cells with dibutyryl cAMP was associated with increase in the levels of PKC epsilon, with no significant changes in its steady-state mRNA levels. The levels of the other isoforms were not altered by the differentiated state. Similarly, no changes in nPKC activity were discerned in either the soluble or particulate fractions when histone or other proteins were used as substrates. These data suggest that the PKC epsilon isoform may be important for the production and maintenance of the differentiated state in NG 108-15 cells. (C) 1994 Academic Press, Inc. C1 UNIV ROMA TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,ROME,ITALY. UNIV MILAN,DEPT PHARMACOL CHEMOTHERAPY & MED TOXICOL,MILAN,ITALY. NATL INST ENVIRONM HLTH SCI,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC. RP BATTAINI, F (reprint author), UNIV MILAN,INST PHARMACOL SCI,VIA BALZARETTI 9,I-20133 MILAN,ITALY. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015; OI Govoni, Stefano/0000-0002-7243-6837; Racchi, Marco/0000-0002-7185-7808 NR 49 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1994 VL 203 IS 3 BP 1423 EP 1431 DI 10.1006/bbrc.1994.2344 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PJ526 UT WOS:A1994PJ52600010 PM 7945290 ER PT J AU SHI, XL LENHART, A MAO, Y AF SHI, XL LENHART, A MAO, Y TI ESR SPIN-TRAPPING INVESTIGATION ON PEROXYNITRITE DECOMPOSITION - NO EVIDENCE FOR HYDROXYL RADICAL PRODUCTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE; HYDROPEROXIDE-HEMATIN; LIPID-PEROXIDATION; SUPEROXIDE; GENERATION; OXIDATION; RESONANCE AB The decomposition of peroxynitrite in the presence of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX) without formation of DMPO/OH. Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Glutathione, cysteine, penicillamine, and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The results show that the decomposition of peroxynitrite did not generate any significant amount of OH radicals, and one-electron reduction of peroxynitrite by ascorbate may be one of the important peroxynitrite detoxification pathways. (C) 1994 Academic Press, Inc. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 32 TC 42 Z9 42 U1 2 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1994 VL 203 IS 3 BP 1515 EP 1521 DI 10.1006/bbrc.1994.2357 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PJ526 UT WOS:A1994PJ52600023 PM 7945300 ER PT J AU LAVU, S SRIVASTAVA, M SRIVASTAVA, SK AF LAVU, S SRIVASTAVA, M SRIVASTAVA, SK TI ANALYSIS OF THE TUMOR-SUPPRESSOR GENE P53 IN XERODERMA-PIGMENTOSUM FIBROBLASTS SO CANCER LETTERS LA English DT Article DE MUTATIONS; P53 GENE; XERODERMA PIGMENTOSUM (XP) ID MUTATIONS; CANCER; DNA; SUNLIGHT AB Genetic risk factor(s) for skin cancers have been described in patients with xeroderma pigmentosum (XP). The tumor suppressor gene, p53, is one of the most frequently mutated genes found in human tumors. To evaluate the role of XP-related genetic defects in the p53 gene, skin fibroblast cell lines derived from XP donors were analysed for mutations in exons 5-9 (the regions of gene highly susceptible for mutations) by single-strand conformation polymorphism (SSCP) and nucleotide sequencing. Of the five XP-derived fibroblasts (complementation group A) and two control fibroblast cell lines, only one XP cell line showed an aberrant SSCP banding pattern in the region of the p53 gene (comprising the 7th exon and neighbouring intronic sequences). Nucleotide sequencing of this region confirmed a mutation in the 7th intron adjacent to the 7th exon, which did not affect the RNA splice site. These results suggest that constitutional/germ-line mutations in the p53 gene may not play a role in the occurrence of skin carcinomas in XP patients. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,CTR PROSTATE DIS RES,BETHESDA,MD 20814. RP LAVU, S (reprint author), US FDA,DIV SCI APPL TECHNOL,COSMET TOXICOL BRANCH,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 15 TC 3 Z9 3 U1 0 U2 2 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 SEP 30 PY 1994 VL 85 IS 1 BP 9 EP 12 DI 10.1016/0304-3835(94)90232-1 PG 4 WC Oncology SC Oncology GA PK647 UT WOS:A1994PK64700002 PM 7923108 ER PT J AU TREUNER, M KOZAK, CA GALLAHAN, D GROSSE, R MULLER, T AF TREUNER, M KOZAK, CA GALLAHAN, D GROSSE, R MULLER, T TI CLONING AND CHARACTERIZATION OF THE MOUSE GENE ENCODING MAMMARY-DERIVED GROWTH INHIBITOR HEART-FATTY ACID-BINDING PROTEIN SO GENE LA English DT Note DE RECOMBINANT DNA; GENE CLONING; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; PSEUDOGENE; CHROMOSOME LOCALIZATION; MAMMARY GLAND ID 9-CIS RETINOIC ACID; DNA-BINDING; DEVELOPMENTAL REGULATION; TRANSCRIPTION FACTOR; X RECEPTOR; EXPRESSION; GLAND; SEQUENCE; INDUCTION; IDENTIFICATION AB From a mouse genomic library we isolated and characterized a gene, Fabph1, encoding mammary-derived growth inhibitor (MDGI)/heart fatty-acid-binding protein (H-FABP). Exon sequences were identical with a MDGI-encoding cDNA isolated previously from the mammary gland of pregnant mice. The product of this gene has also been detected in heart, where it had been termed H-FABP. It has an intron/exon structure similar to other FABP-encoding genes. In addition to this expressed gene, we isolated a related intronless pseudogene, Fabph-ps, with an open reading frame which was highly conserved when compared with Fabph1. Fabph1 was positioned on chromosome (Chr) 4 using interspecies crosses. Analysis of somatic cell hybrids was used to assign Fabph-ps to Chr 10, and another MDGI/H-FABP-related sequence locus, Fabph-rs1, to Chr 8. A Mus spretus-specific related sequence, Fabph-rs2, was identified on Chr 17 by analysis of interspecies crosses. The 5'-flanking region of Fabph1 contains putative transcription factor-binding elements which could account for its constitutive expression in muscle tissue, as well as for its developmental stage-dependent expression in mammary epithelium. C1 NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. MAX DELBRUCK CTR MOLEC MED,D-13122 BERLIN,GERMANY. NCI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 38 TC 60 Z9 65 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 30 PY 1994 VL 147 IS 2 BP 237 EP 242 DI 10.1016/0378-1119(94)90073-6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA PK880 UT WOS:A1994PK88000014 PM 7926807 ER PT J AU DELUCA, AM JOHNSTONE, PAS OLLAYOS, CW BACHER, JD TERRILL, RE KINSELLA, TJ SINDELAR, WF AF DELUCA, AM JOHNSTONE, PAS OLLAYOS, CW BACHER, JD TERRILL, RE KINSELLA, TJ SINDELAR, WF TI TOLERANCE OF THE BLADDER TO INTRAOPERATIVE RADIATION IN A CANINE MODEL - A 5-YEAR FOLLOW-UP SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE INTRAOPERATIVE RADIATION; BLADDER; URETERS; NORMAL TISSUE TOLERANCE ID BEAM RADIOTHERAPY; THERAPY; CANCER; IORT AB Purpose: Late effects of intraoperative radiation therapy (IORT) on bladder we Methods and Materials: After laporatomy and cystotomy in adult female foxhounds weighing 25-35 kg, 12 MeV electrons were delivered intraoperatively to a 5 cm circular bladder held which included the trigone and both uretero-vesicle junctions. Each animal received doses of 0, 20, 25, 30, 35, or 40 Gy. All the dogs were followed 5 years postoperatively. An unoperated dog receiving no surgery or radiation treatment was followed as a control. Close clinical monitoring was performed with regular cystometrics and intravenous pyelography. Animals were killed as scheduled with complete necropsies, including histopathology, with special attention to genitourinary structures. Results: There were no acute or late bladder complications detected clinically in any animal. The dog receiving 30 Gy IORT developed rhabdomyosarcoma in the treatment field at 58 months. On follow-up testing over 5 years, there was no loss of bladder contractility on cystometry, and mild changes in the ureters on intravenous pyleography when animals receiving IORT were compared with baseline pretreatment values or with control animals. Histologically, a difference was evident between irradiated and unirradiated animals, but the changes were not clearly dose-related. Conclusion: Intraoperative radiation therapy may by safely delivered to the canine bladder with few acute or chronic complications. It is an approach which has potential for clinical use and should continue to be explored in human clinical trials. C1 NCI, SURG BRANCH, BETHESDA, MD 20892 USA. NCI, OFF ANIM SCI LAB, BETHESDA, MD 20892 USA. NIH, NATL CTR RES RESOURCES, VET RESOURCES PROGRAM, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DIV SURG PATHOL, BETHESDA, MD 20889 USA. RP DELUCA, AM (reprint author), NCI, RADIAT BIOL BRANCH, BLDG 10 B3B69, BETHESDA, MD 20892 USA. NR 21 TC 9 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 30 PY 1994 VL 30 IS 2 BP 339 EP 345 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PK072 UT WOS:A1994PK07200011 PM 7928460 ER PT J AU IVANOVA, VS HATCH, CL BONNER, WM AF IVANOVA, VS HATCH, CL BONNER, WM TI CHARACTERIZATION OF THE HUMAN HISTONE H2A.X GENE - COMPARISON OF ITS PROMOTER WITH OTHER H2A GENE PROMOTERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; CELL-CYCLE; DNA-REPLICATION; S-PHASE; EXPRESSION; SEQUENCE; PROTEIN; PHOSPHORYLATION; TRANSCRIPTION; BINDING AB The human gene for the replication-unlinked histone protein H2A.X is a naturally occurring chimera that contains a replication-unlinked promoter yet produces a stemloop mRNA characteristic of replication-linked histone genes. Consistent with the latter attribute, the H2A.X gene was found to lack introns. The promoter of the H2A.X gene was localized to a 120-base pair region upstream of the transcription start site, a region which included a TATA and two CCAAT sequence elements. The proximal of the two CCAAT elements was shown to be an important determinant of H2A.X gene promoter activity. In a comparative study with the CCAAT elements from the replication-linked H2A.1a gene and the replication-unlinked H2A.Z gene, the proximal CCAAT element of the H2A.X gene was found to bind nuclear factors also bound by CCAAT elements in the latter but not in the former, The specificity of the replication-unlinked H2A.X and H2A.Z gene promoters for CCAAT-binding transcription factors appeared to also reside in short homologous sequences about 10 base pairs away on either side of the CCAAT sequence. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 34 TC 11 Z9 11 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 SEP 30 PY 1994 VL 269 IS 39 BP 24189 EP 24194 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ346 UT WOS:A1994PQ34600055 PM 7929075 ER PT J AU RABEN, N NICHOLS, R DOHLMAN, J MCPHIE, P SRIDHAR, V HYDE, C LEFF, R PLOTZ, P AF RABEN, N NICHOLS, R DOHLMAN, J MCPHIE, P SRIDHAR, V HYDE, C LEFF, R PLOTZ, P TI A MOTIF IN HUMAN HISTIDYL-TRANSFER-RNA SYNTHETASE WHICH IS SHARED AMONG SEVERAL AMINOACYL-TRANSFER-RNA SYNTHETASES IS A COILED-COIL THAT IS ESSENTIAL FOR ENZYMATIC-ACTIVITY AND CONTAINS THE MAJOR AUTOANTIGENIC EPITOPE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; CHAIN-RELEASE FACTOR; ESCHERICHIA-COLI; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE; SACCHAROMYCES-CEREVISIAE; SECONDARY-STRUCTURE; CIRCULAR-DICHROISM; ANTI-JO-1 ANTIBODY; TERMINAL EXTENSION; MYOSITIS AB In myositis, disease-specific autoantibodies may be directed against an aminoacyl-tRNA synthetase, usually histidyl-tRNA synthetase. To explore the basis for this phenomenon, we have made recombinant histidyl-tRNA synthetase in the baculovirus system. It was enzymatically active and recognized by human autoantibodies. A truncated protein lacking the first 60 amino acids was inactive as an antigen and as an enzyme. This region is within the first two exons, is predicted to have a coiled-coil configuration, and is found in some other synthetases but not in Escherichia coli or yeast histidyl-tRNA synthetase. Circular dichroism showed that the peptides from this region (amino acids 1-60 and 1-47) have the predicted high alpha-helical content, but smaller fragments (1-30, 14-45, and 31-60) do not. The peptides with a high alpha-helical content could inhibit autoantibodies almost completely, whereas the smaller peptides were unable to do so. The amino acid sequence of this coiled-coil domain in human histidyl-tRNA synthetase resembles the sequence of the extended this coiled-coil arm near the NH2 terminus of bacterial seryl-tRNA synthetase as well as similar regions in some eukaryotic aminoaayl-tRNA synthetases, raising the possibility that this domain serves a similar tRNA-stabilizing role and has been preserved from a common ancestor. C1 NIDDK,BETHESDA,MD 20892. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP RABEN, N (reprint author), NIAMSD,CTR CLIN 9N244,ARTHRIT & RHEUMATISM BRANCH,CONNECT TISSUE DIS SECT,BETHESDA,MD 20892, USA. NR 62 TC 60 Z9 64 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 SEP 30 PY 1994 VL 269 IS 39 BP 24277 EP 24283 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ346 UT WOS:A1994PQ34600066 PM 7523371 ER PT J AU DING, L SETO, BL AHMED, SA COLEMAN, WG AF DING, L SETO, BL AHMED, SA COLEMAN, WG TI PURIFICATION AND PROPERTIES OF THE ESCHERICHIA-COLI K-12 NAD-DEPENDENT NUCLEOTIDE DIPHOSPHOSUGAR EPIMERASE, ADP-L-GLYCERO-D-MANNOHEPTOSE 6-EPIMERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIPHOSPHATE GALACTOSE 4-EPIMERASE; RFAD GENE; BINDING; BIOSYNTHESIS; ENZYME; EXPRESSION; ADENOSINE; MECHANISM; REDUCTION; SUBSTRATE AB The Escherichia coli K-12 NAD-dependent nucleotide-diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase, catalyzes the conversion of ADP-D-glycero-D-mannoheptose to ADP-L-glycero-D-mannoheptose. ADP-L-glycero-D-mannoheptose is a key intermediate of lipopolysaccharide inner core biosynthesis in several genera of Gram-negative bacteria. Sedimentation equilibrium and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified epimerase revealed that the native enzyme has a molecular mass of 240 kDa and a subunit molecular weight of 37,000 +/- 3,000. Lectin binding studies of the purified epimerase indicated that the protein is glycosylated. There was 1 mol of tightly bound NAD(+) per enzyme subunit. Variable but small fractions of purified preparations of epimerase are highly fluorescent and contain NADH. The native enzyme can be resolved into apoenzyme and NAD(+) by acidic ammonium sulfate precipitation. The catalytic activity can be reconstituted with the addition of NAD(+) to the apoenzyme. Optimum pH range for enzyme activity is broad, between 5.5 and 9.5. It exhibits a temperature optimum at 42 degrees C. The K-m and V-max for the substrate is 0.1 mM and 46 mu mol 30 min(-1) mg(-1), respectively. The native enzyme displays UV and fluorescence spectra that are consistent with the presence of enzyme bound NAD(+). CD spectra of the holoepimerase indicate 11% alpha-helical and 36% beta-sheet structures. C1 NIDDK, BIOCHEM PHARMACOL LAB, PHARMACOL SECT, BETHESDA, MD 20892 USA. NIDDK, BIOCHEM PHARMACOL LAB, ENZYME STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. NR 32 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 30 PY 1994 VL 269 IS 39 BP 24384 EP 24390 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ346 UT WOS:A1994PQ34600083 PM 7929099 ER PT J AU GARRITSEN, A SIMONDS, WF AF GARRITSEN, A SIMONDS, WF TI MULTIPLE DOMAINS OF G-PROTEIN-BETA CONFER SUBUNIT SPECIFICITY IN BETA-GAMMA-INTERACTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING REGULATORY PROTEINS; LIMITED PROTEOLYSIS; COILED-COIL; TRANSDUCIN; ASSOCIATION; PRENYLATION; EXPRESSION; ANTIBODIES; DIMERS; CELLS AB The expression and assembly of particular combinations of beta and gamma subunit isoforms into beta gamma heterodimers may contribute to the specificity of signal transduction mediated by heterotrimeric guanine nucleotide binding regulatory proteins. Using a transient transfection paradigm to examine selectivity in beta gamma heterodimer formation, we find that gamma(1) interacts with beta(1) but not with beta(2), while both beta subunits interact with gamma(2) and that a beta(2)/beta(1) chimera containing the N-terminal 41 residues of beta(2) retained a beta(1), phenotype. These results confirm previous reports and imply that a structure or structures between residues 42 and 340 in the C-terminal region of the beta subunit imparts the ability to distinguish between gamma chains. Extending this chimeric approach to further localize the regions of beta important for selectivity between gamma subunits, we find that the region of beta(1) or beta(2) between residue 215 and the C terminus is sufficient to confer the parental phenotype. Additional mutants implicate multiple regions of beta, including discrete residues in the variable connecting segments joining conserved elements of the fifth and sixth GH-WD repeats toward the C terminus of beta. These findings suggest a multidomain interaction between beta and gamma. C1 NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. NR 33 TC 41 Z9 41 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 SEP 30 PY 1994 VL 269 IS 39 BP 24418 EP 24423 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ346 UT WOS:A1994PQ34600088 PM 7929103 ER PT J AU KRUTH, HS SKARLATOS, SI GAYNOR, PM GAMBLE, W AF KRUTH, HS SKARLATOS, SI GAYNOR, PM GAMBLE, W TI PRODUCTION OF CHOLESTEROL-ENRICHED NASCENT HIGH-DENSITY-LIPOPROTEINS BY HUMAN MONOCYTE-DERIVED MACROPHAGES IS A MECHANISM THAT CONTRIBUTES TO MACROPHAGE CHOLESTEROL EFFLUX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN APOLIPOPROTEIN-E; HYPERLIPIDEMIC RABBIT; A-I; ATHEROSCLEROSIS; METABOLISM; TRANSPORT; SECRETION; VESICLES; PLAQUES; ATHEROGENESIS AB Atherosclerotic lesions have a lipid core containing crystals and liposomes enriched in unesterified cholesterol as well as numerous monocyte-macrophages enriched in cholesteryl ester. Sufficient amounts of plasma-derived high density lipoproteins (HDL) may not reach and efficiently remove the cholesterol deposited in lesion macrophages or in the lipid core of lesions. We examined the potential of human monocyte-macrophages to produce nascent HDL and to solubilize cholesterol derived from interaction of monocyte-macrophages with lipoprotein and non-lipoprotein sources of cholesterol. Monocyte-macrophages produced discoidal (25 +/- 6 nm long and 6 +/- 1 nm wide (mean +/- S.D.)) and vesicular (89 +/- 41 nm in diameter) lipoprotein particles following and during enrichment of macrophages with cholesterol from acetylated low density lipoprotein (AcLDL) or cholesterol crystals. During cholesterol enrichment, discoidal particles progressively accumulated in the medium for up to 6 days. In contrast, vesicles did not increase past 2 days of incubation. Both the discoidal and vesicular lipoprotein particles had a peak density of about 1.09-1.10 g/ml, The discoidal particles contained apolipoprotein E (apoE), whereas the vesicles contained a major protein constituent with a molecular mass of 22,000 daltons. The vesicles did not contain detectable apoE and the 22,000-dalton protein was not the 22,000-dalton thrombolytic fragment of apoE. Following cholesterol enrichment of macrophages with AcLDL or cholesterol crystals, macrophages excreted much of their accumulated cholesterol, even in the absence of exogenously added cholesterol accepters. Most of this excreted cholesterol was recovered from the culture medium and was carried in the apoE discoidal particles that showed cholesterol enrichment up to a 2:1 unesterified cholesterol to phospholipid molar ratio. The findings suggest that sufficient production of these nascent HDL by macrophages within atherosclerotic lesions should facilitate removal of cellular and extracellular cholesterol, even in the absence of plasma-derived HDL. C1 OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,CORVALLIS,OR 97331. RP KRUTH, HS (reprint author), NHLBI,EXPTL ATHEROSCLEROSIS SECT,BLDG 10,RM 5N-113,BETHESDA,MD 20892, USA. NR 44 TC 77 Z9 77 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 SEP 30 PY 1994 VL 269 IS 39 BP 24511 EP 24518 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ346 UT WOS:A1994PQ34600101 PM 7929116 ER PT J AU KIM, HO JI, XD MELMAN, N OLAH, ME STILES, GL JACOBSON, KA AF KIM, HO JI, XD MELMAN, N OLAH, ME STILES, GL JACOBSON, KA TI STRUCTURE-ACTIVITY-RELATIONSHIPS OF 1,3-DIALKYLXANTHINE DERIVATIVES AT RAT A(3) ADENOSINE RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; A1-ADENOSINE RECEPTORS; SELECTIVE ANTAGONISTS; POTENT; CELLS; BRAIN AB 1,3-Dialkylxanthine analogues containing carboxylic acid and other charged groups on 8-position substituents were synthesized. These derivatives were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells using the new radioligand [I-125]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide), and at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. A synthetic strategy for introducing multiple carboxylate groups at the 8-position using iminodiacetic acid derivatives was explored. The presence of a sulfonate, a carboxylate, or multiple carboxylate soups did not result in a significant enhancement of affinity at rat A(3) receptors, although as previously observed an anionic group tended to diminish potency at Ar and A(2a) receptors. The rat A(3) receptor affnity was not highly dependent on the distance of a carboxylate group from the xanthine pharmacophore. 2-Thio vs 2-oxo substitution favored A(3) potency, and 8-alkyl vs 8-aryl substitution favored A(3) selectivity, although few derivatives were truly selective for rat A(3) receptors. 1,3-Dimethyl-8-(3-carboxypropyl)-2-thioxanthine was 7-fold selective for A(3) VS A(2)a receptors. 1,3,7-Trimethyl-8-(trans-2-carboxyvinyl) was somewhat selective for A(3) VS A(1) receptors. For 8-arylxanthines affinity at A(3) receptors was enhanced by 1,3-dialkyl substituents, in the order dibutyl > dipropyl > diallyl. C1 NIDDKD,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 35 TC 63 Z9 64 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 30 PY 1994 VL 37 IS 20 BP 3373 EP 3382 DI 10.1021/jm00046a022 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PJ909 UT WOS:A1994PJ90900022 PM 7932565 ER PT J AU ZHAO, M KLEINMAN, HK MOKOTOFF, M AF ZHAO, M KLEINMAN, HK MOKOTOFF, M TI SYNTHETIC LAMININ-LIKE PEPTIDES AND PSEUDOPEPTIDES AS POTENTIAL ANTIMETASTATIC AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EXPERIMENTAL METASTASIS FORMATION; BASEMENT-MEMBRANE; RECEPTOR ANTAGONISTS; MELANOMA-CELLS; BOND ISOSTERE; TUMOR-GROWTH; AMINO-ACIDS; ANALOGS; PENTAPEPTIDE; INHIBITION AB This paper describes our efforts to study structure-activity relationships, improve the antimetastatic potency, and limit the in vivo enzymatic degradation of YIGSR-NH2, a synthetic peptide from the B1 chain of laminin, which reportedly has potential as an antimetastatic agent. To this end we have synthesized a series of psi(CH2NH) peptide analogs (5-9) of YIGSR-NH2 and a number of peptides in which the Tyr residue was replaced with D-Tyr (1), Phe (2), Phe (p-F) (3), and Phe(p-NH2) (4). All new peptides were assayed in vitro for their ability to promote cell attachment in both B16F10 mouse melanoma cells and HT-1080 human fibrosarcoma cells. On the basis of the in vitro assay results, peptides 3-5, 8, and 9 were tested in vivo for their ability to inhibit tumor metastasis to the lungs in mice that were coinjected in the tail vein with B16F10 melanoma cells and 1 mg of peptide. In summary, of the nine new peptides only the Phe(p-NH2) peptide 4 showed consistent in vitro cell attachment activity, but only low in vivo antimetastatic activity. C1 UNIV PITTSBURGH, SCH PHARM, DEPT PHARMACEUT SCI, PITTSBURGH, PA 15261 USA. NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [RR04664-01] NR 49 TC 17 Z9 17 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 30 PY 1994 VL 37 IS 20 BP 3383 EP 3388 DI 10.1021/jm00046a023 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PJ909 UT WOS:A1994PJ90900023 PM 7932566 ER PT J AU RODRIGUEZ, JB MARQUEZ, VE NICKLAUS, MC MITSUYA, H BARCHI, JJ AF RODRIGUEZ, JB MARQUEZ, VE NICKLAUS, MC MITSUYA, H BARCHI, JJ TI CONFORMATIONALLY LOCKED NUCLEOSIDE ANALOGS - SYNTHESIS OF DIDEOXYCARBOCYCLIC NUCLEOSIDE ANALOGS STRUCTURALLY RELATED TO NEPLANOCIN-C SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUGAR-PHOSPHATE BACKBONE; NUCLEIC-ACID ANALOGS; REVERSE-TRANSCRIPTASE; BICYCLO<3.1.0>HEXANE DERIVATIVES; CARBOCYCLIC ANALOGS; 2',3'-DIDEOXYCYTIDINE; 2',3'-DIDEOXYNUCLEOSIDES; SPECTROSCOPY; INVITRO AB The glycon moiety of nucleosides in solution is known to exist in a rapid dynamic equilibrium between extreme northern and southern conformations as defined by the pseudorotation cycle. The concept of preparing rigid nucleoside analogues with the glycan conformation locked in one of these two extremes was tested with the synthesis of some cyclopropane-fused dideoxycarbocyclic nucleosides, similar to the well-known class of anti-HIV active dideoxynucleosides. The new compounds described here are dideoxynucleoside analogues of the fermentation product neplanocin C (6) which exhibits a typical northern geometry for its 6-oxabicyclo[3.1.0]hexane pseudosugar moiety. However, in view of the lability of the epoxide ring in this system, the equivalent cyclopropane-fused bicyclo[3.1.0]hexane system was used instead to prepare the corresponding dideoxynucleoside analogues bearing all the common bases [(+)-9-13]. Due to the well-documented preference of unrestricted bicyclo[3.1.0]hexane systems to exist exclusively in a boat conformation, the resulting nucleosides are structurally locked in a typical northen conformation similar to that of neplanocin C. The locked northern conformation in these nucleosides remained unchanged in solution in the 20-80 degrees C temperature range according to variable temperature H-1 NMR studies. For the synthesis of these compounds, racemic trans-1-[(benzyloxy)methyl]-4-hydroxybicyclo[3.1.0]hexane [(+/-)-18] was prepared by a samarium-promoted cyclopropanation reaction with the antecedent cyclopentenol. AU of the bases were incorporated under Mitsunobu conditions and converted to the desired final products following a standard methodology. Anti-HIV evaluation revealed that only the adenosine analogue (+/-)-9 possessed enough activity to warrant resolution into its optical antipodes. This was realized by chiral HPLC chromatography to give the individual enantiomers (-)-32 and (+)-33. Adenosine deaminase was used to identify isomer (+)-33 as the enantiomer with the ''natural'' configuration which was solely responsible for the observed biological activity and toxicity of (+/-)-9. It is possible that the exclusive northern conformation adopted by these nucleosides reduces their substrate affinity far the various activating kinases, except in the case of the adenosine analogue. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RI Nicklaus, Marc/N-4183-2014; Barchi Jr., Joseph/N-3784-2014; OI Rodriguez, Juan Bautista/0000-0002-5180-096X NR 48 TC 93 Z9 93 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 30 PY 1994 VL 37 IS 20 BP 3389 EP 3399 DI 10.1021/jm00046a024 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PJ909 UT WOS:A1994PJ90900024 PM 7932567 ER PT J AU LI, LP WANG, HK KUO, SC WU, TS MAUGER, A LIN, CM HAMEL, E LEE, KH AF LI, LP WANG, HK KUO, SC WU, TS MAUGER, A LIN, CM HAMEL, E LEE, KH TI ANTITUMOR AGENTS .155. SYNTHESIS AND BIOLOGICAL EVALUATION OF 3',6,7-SUBSTITUTED 2-PHENYL-4-QUINOLONES AS ANTIMICROTUBULE AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUBULIN; COLCHICINE; COMBRETASTATIN-A-4; PODOPHYLLOTOXIN; INHIBITION; SEPARATION; BINDING AB A series of 3',6,7-substituted 2-phenyl-4-quinolones were designed and synthesized as antimitotic antitumor agents. All compounds showed cytotoxic effects (log GI(50) less than or equal to -4.0; log drug molar concentration required to cause 50% inhibition) against the growth of a variety of human tumor cell lines, including those derived from solid tumors such as non-small cell lung, colon, central nervous system, ovary, prostate, and breast cancers, when evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. The most potent compound (26) demonstrated strong cytotoxic effects with GI(50) values in the nanomolar or subnanomolar range in almost all the tumor cell lines. Compound 26 was also a potent inhibitor of tubulin polymerization and radiolabeled colchicine binding to tubulin, with activity comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG 400,TAIWAN. NATL CHENG KUNG UNIV,DEPT CHEM,TAINAN 70101,TAIWAN. NCI,DRUG SYNTH & CHEM BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [CA 17625] NR 16 TC 126 Z9 132 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 30 PY 1994 VL 37 IS 20 BP 3400 EP 3407 DI 10.1021/jm00046a025 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PJ909 UT WOS:A1994PJ90900025 PM 7932568 ER PT J AU MAY, EL ACETO, MD BOWMAN, ER BENTLEY, C MARTIN, BR HARRIS, LS MEDZIHRADSKY, F MATTSON, MV JACOBSON, AE AF MAY, EL ACETO, MD BOWMAN, ER BENTLEY, C MARTIN, BR HARRIS, LS MEDZIHRADSKY, F MATTSON, MV JACOBSON, AE TI ANTIPODAL ALPHA-N-(METHYL THROUGH DECYL)-N-NORMETAZOCINES (5,9-ALPHA-DIMETHYL-2'-HYDROXY-6,7-BENZOMORPHANS) - IN-VITRO AND IN-VIVO PROPERTIES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG BRAIN; PROTEIN-COUPLED RECEPTORS; DELTA-OPIOID RECEPTOR; SIGMA-RECEPTORS; BINDING-SITES; RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; H-3 (+)-PENTAZOCINE; N-NORMETAZOCINES AB The enantiomeric (-)- and (+)-N-(methyl through decyl) normetazocines (5,9 alpha-dimethyl-2'hydroxy-6,7-benzomorphans) were synthesized and their in vitro and in vivo activities determined. Increasingly bulky enantiomeric N-alkyl homologs were prepared until their interaction with the or receptor decreased and their insolubility became a hindrance to their evaluation in vivo and/or in vitro. The(-)-methyl, -pentyl, -hexyl, and -heptyl homologs were essentially as potent as, or more potent than, morphine in the tail-flick, phenylquinone, and hot-plate assays for antinociceptive activity; the (-)-propyl homolog had narcotic antagonist activity between that of nalorphine and naloxone in the tail-flick vs morphine assay, and it also displayed antagonist properties in the single-dose suppression assay in the rhesus monkey. The antinociceptively potent (-)-heptyl homolog did not substitute for morphine in monkeys but did show morphine-like properties in a primary physical-dependence study in continuously infused rats. All five potent compounds showed high affinity for the mu opioid receptor from both rat and monkey preparations and the kappa opioid receptor (<0.05 mu M), and all except the (-)-methyl homolog interacted reasonably well at the delta receptor (K-i <0.1 mu M). The (-)-propyl compound was equipotent (K-i 1.5-2.0 nM) at mu and kappa receptors. The pattern of interaction of the (-)-enantiomeric homologs with mu receptors from rat and monkey preparations was similar, but not identical. The enantioselectivity of the homologs for mu receptors was greater in the rat than in the monkey preparation for all but the N-H and butyl compounds, and the enantioselectivity of the lower homologs (methyl through butyl) for the mu (monkey) receptor was greater than for the kappa or delta receptors. However, bulkier homologs (hexyl through decyl) displayed higher enantioselectivity at kappa or delta receptors than at the mu (monkey) receptor. The (+)-butyl through (+)-octyl homologs were essentially equipotent with, or more potent than, (+)-pentazocine at the sigma receptor. Only the (+)-H and (+)-methyl homologs had high affinity(<0.05 mu M) at PCP binding sites. C1 UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,ANN ARBOR,MI 48109. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP MAY, EL (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298, USA. FU NIDA NIH HHS [DA 271-90-7200, DA00490, DA02396] NR 83 TC 44 Z9 44 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 30 PY 1994 VL 37 IS 20 BP 3408 EP 3418 DI 10.1021/jm00046a026 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PJ909 UT WOS:A1994PJ90900026 PM 7932569 ER PT J AU BOGUSKI, MS TOLSTOSHEV, CM BASSETT, DE AF BOGUSKI, MS TOLSTOSHEV, CM BASSETT, DE TI GENE DISCOVERY IN DBEST SO SCIENCE LA English DT Letter ID EXPRESSED SEQUENCE TAGS; HUMAN GENOME PROJECT C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. RP BOGUSKI, MS (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 12 TC 111 Z9 128 U1 4 U2 25 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 30 PY 1994 VL 265 IS 5181 BP 1993 EP 1994 DI 10.1126/science.8091218 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ912 UT WOS:A1994PJ91200002 PM 8091218 ER PT J AU COX, DR GREEN, ED LANDER, ES COHEN, D MYERS, RM AF COX, DR GREEN, ED LANDER, ES COHEN, D MYERS, RM TI ASSESSING MAPPING PROGRESS IN THE HUMAN-GENOME-PROJECT SO SCIENCE LA English DT Editorial Material ID CHROMOSOMES; MODEL C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. CTR ETUD POLYMORPHISME HUMAIN,F-75010 PARIS,FRANCE. RP COX, DR (reprint author), STANFORD UNIV,DEPT GENET,STANFORD,CA 94305, USA. NR 7 TC 29 Z9 29 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 30 PY 1994 VL 265 IS 5181 BP 2031 EP 2032 DI 10.1126/science.8091223 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ912 UT WOS:A1994PJ91200018 PM 8091223 ER PT J AU KORN, EL MIDTHUNE, D CHEN, TT RUBINSTEIN, LV CHRISTIAN, MC SIMON, RM AF KORN, EL MIDTHUNE, D CHEN, TT RUBINSTEIN, LV CHRISTIAN, MC SIMON, RM TI A COMPARISON OF 2 PHASE-I TRIAL DESIGNS SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS; CANCER AB Phase I cancer chemotherapy trials are designed to determine rapidly the maximum tolerated dose of a new agent for further study. A recently proposed Bayesian method, the continual reassessment method, has been suggested to offer an improvement over the standard design of such trials. We find the previous comparisons did not completely address the relative performance of the designs as they would be used in practice. Our results indicate that with the continual reassessment method, more patients will be treated at very high doses and the trials will take longer to complete. We offer some suggested improvements to both the standard design and the Bayesian method. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP KORN, EL (reprint author), NCI,BIOMETR RES BRANCH,EPN-739,BETHESDA,MD 20892, USA. NR 10 TC 146 Z9 147 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1994 VL 13 IS 18 BP 1799 EP 1806 DI 10.1002/sim.4780131802 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PH440 UT WOS:A1994PH44000001 PM 7997713 ER PT J AU GROSSMAN, J PARMAR, MKB SPIEGELHALTER, DJ FREEDMAN, LS AF GROSSMAN, J PARMAR, MKB SPIEGELHALTER, DJ FREEDMAN, LS TI A UNIFIED METHOD FOR MONITORING AND ANALYZING CONTROLLED TRIALS SO STATISTICS IN MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; GROUP SEQUENTIAL-METHODS; INTERIM ANALYSES; OVERVIEWS; DESIGN AB Group sequential methods are becoming increasingly popular for monitoring and analysing large controlled trials, especially clinical trials. They not only allow trialists to monitor the data as it accumulates, but also reduce the expected sample size. Such methods are traditionally based on preserving the overall type I error by increasing the conservatism of the hypothesis tests performed at any single analysis. Using methods which are based on hypothesis testing in this way makes point estimation and the calculation of confidence intervals difficult and controversial. We describe a class of group sequential procedures based on a single parameter which reflects initial scepticism towards unexpectedly large effects. These procedures have good expected and maximum sample sizes, and lead to natural point and interval estimates of the treatment difference. Hypothesis tests, point estimates and interval estimates calculated using this procedure are consistent with each other, and tests and estimates made at the end of the trial are consistent with interim tests and estimates. This class of sequential tests can be considered in both a traditional group sequential manner or as a Bayesian solution to the problem. C1 UNIV CAMBRIDGE,ADDENBROOKES HOSP,MED RES COUNCIL,BIOSTAT UNIT,CAMBRIDGE CB2 2QQ,ENGLAND. MRC,CANC TRIALS OFF,CAMBRIDGE,ENGLAND. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. RP GROSSMAN, J (reprint author), UNIV SYDNEY,DEPT COMMUNITY MED,SYDNEY,NSW 2006,AUSTRALIA. NR 20 TC 21 Z9 21 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1994 VL 13 IS 18 BP 1815 EP 1826 DI 10.1002/sim.4780131804 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PH440 UT WOS:A1994PH44000003 PM 7997715 ER PT J AU CANNON, RO AF CANNON, RO TI IMIPRAMINE IN PATIENTS WITH CHEST PAIN DESPITE NORMAL CORONARY ANGIOGRAMS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID POSTHERPETIC NEURALGIA; DIABETIC NEUROPATHY; AMITRIPTYLINE RP CANNON, RO (reprint author), NIH,BETHESDA,MD 20892, 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 SEP 29 PY 1994 VL 331 IS 13 BP 882 EP 883 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PH530 UT WOS:A1994PH53000029 ER PT J AU GALLO, RC AF GALLO, RC TI KAPOSIS-SARCOMA, VASCULAR-PERMEABILITY, AND SCIENTIFIC INTEGRITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP GALLO, RC (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 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 SEP 28 PY 1994 VL 272 IS 12 BP 916 EP 917 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PG737 UT WOS:A1994PG73700008 PM 8084052 ER PT J AU ENSOLI, B AF ENSOLI, B TI KAPOSIS-SARCOMA, VASCULAR-PERMEABILITY, AND SCIENTIFIC INTEGRITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP ENSOLI, B (reprint author), NCI,BETHESDA,MD 20892, USA. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 7 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 SEP 28 PY 1994 VL 272 IS 12 BP 918 EP 919 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PG737 UT WOS:A1994PG73700011 PM 8084055 ER PT J AU BRYANT, JL AF BRYANT, JL TI KAPOSIS-SARCOMA, VASCULAR-PERMEABILITY, AND SCIENTIFIC INTEGRITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP BRYANT, JL (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 1 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 SEP 28 PY 1994 VL 272 IS 12 BP 921 EP 921 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PG737 UT WOS:A1994PG73700014 PM 8084056 ER PT J AU POLLACK, MM CUERDON, TT PATEL, KM RUTTIMANN, UE GETSON, PR LEVETOWN, M AF POLLACK, MM CUERDON, TT PATEL, KM RUTTIMANN, UE GETSON, PR LEVETOWN, M TI IMPACT OF QUALITY-OF-CARE FACTORS ON PEDIATRIC INTENSIVE-CARE UNIT MORTALITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HOSPITAL CHARACTERISTICS; VOLUME; OUTCOMES; PERFECT; TIME AB Objective.-To determine the importance of the following care factors previously associated with hospital quality on survival from pediatric intensive care: size of the intensive care unit (ICU), medical school teaching status of the hospital housing the ICU, specialist status (pediatric intensivist), and unit coordination. Design.-After a national survey, consecutive case series were collected at 16 sites randomly selected to represent unique combinations of quality-of-care factors. Setting.-Pediatric ICUs. Patients.-Consecutive admissions to each site. Main Outcome Measure.-Patient mortality adjusted for physiologic status, diagnosis, and other mortality risk factors. Results.-There were 5415 pediatric ICU admissions and 248 ICU deaths. The ICUs differed significantly with respect to descriptive variables, including mortality (range, 2.2% to 16.4%). Analysis of risk-adjusted mortality indicated that the hospital teaching status and the presence of a pediatric intensivist were significantly associated with a patient's chance of survival. The probability of patient survival after hospitalization in an ICU located in a teaching hospital was decreased (relative odds of dying, 1.79; 95% confidence interval [CI], 1.23 to 2.61; P=.002). In contrast, the probability of patient survival after hospitalization in an ICU with a pediatric intensivist was improved (relative odds of dying, 0.65; 95% CI, 0.44 to 0.95; P=.027). Post hoc analysis indicated that the higher severity-adjusted mortality in teaching hospitals may be explained by the presence of residents caring for ICU patients. Conclusion.-Characteristics indicative of the best overall hospital quality may not be associated, or may be negatively associated, with quality of care in specialized care areas, including the pediatric ICU. C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED,DEPT ANESTHESIOL,WASHINGTON,DC. CHILDRENS NATL MED CTR,DEPT PEDIAT,WASHINGTON,DC. CHILDRENS NATL MED CTR,DEPT CRIT CARE MED,WASHINGTON,DC. NIAAA,BETHESDA,MD. RP POLLACK, MM (reprint author), CHILDRENS NATL MED CTR,CHILDRENS RES INST,CTR HLTH SERV & CLIN RES,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. FU PHS HHS [MCH-110584] NR 30 TC 147 Z9 151 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 SEP 28 PY 1994 VL 272 IS 12 BP 941 EP 946 DI 10.1001/jama.272.12.941 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PG737 UT WOS:A1994PG73700021 PM 8084061 ER PT J AU ELEY, JW HILL, HA CHEN, VW AUSTIN, DF WESLEY, MN MUSS, HB GREENBERG, RS COATES, RJ CORREA, P REDMOND, CK HUNTER, CP HERMAN, AA KURMAN, R BLACKLOW, R SHAPIRO, S EDWARDS, BK AF ELEY, JW HILL, HA CHEN, VW AUSTIN, DF WESLEY, MN MUSS, HB GREENBERG, RS COATES, RJ CORREA, P REDMOND, CK HUNTER, CP HERMAN, AA KURMAN, R BLACKLOW, R SHAPIRO, S EDWARDS, BK TI RACIAL-DIFFERENCES IN SURVIVAL FROM BREAST-CANCER - RESULTS OF THE NATIONAL-CANCER-INSTITUTE BLACK/WHITE CANCER SURVIVAL STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BLACK-WHITE DIFFERENCES; SOCIOECONOMIC-STATUS; WOMEN; STAGE; RACE; EXPERIENCE; ESTROGEN; PROJECT; DELAY AB Objective.-To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. Design and Participants.-Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. Main Outcome Measure.-Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. Results.-After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio=1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer-specific mortality. Conclusions.-Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. WAKE FOREST UNIV,CTR COMPREHENS CANC,WINSTON SALEM,NC. UNIV PITTSBURGH,DEPT BIOSTAT,PITTSBURGH,PA 15261. OFF RES WOMENS HLTH,BETHESDA,MD. NICHHD,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT OBSTET GYNECOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD. RP ELEY, JW (reprint author), EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA 30322, USA. FU NCI NIH HHS [N01-CN-45174, N01-CN-35043, N01-CN-25501] NR 26 TC 416 Z9 417 U1 3 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 28 PY 1994 VL 272 IS 12 BP 947 EP 954 DI 10.1001/jama.272.12.947 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PG737 UT WOS:A1994PG73700022 PM 8084062 ER PT J AU KREITMAN, RJ PURI, RK LELAND, P LEE, B PASTAN, I AF KREITMAN, RJ PURI, RK LELAND, P LEE, B PASTAN, I TI SITE-SPECIFIC CONJUGATION TO INTERLEUKIN-4 CONTAINING MUTATED CYSTEINE RESIDUES PRODUCES INTERLEUKIN 4-TOXIN CONJUGATES WITH IMPROVED BINDING AND ACTIVITY SO BIOCHEMISTRY LA English DT Article ID 3-DIMENSIONAL SOLUTION STRUCTURE; MAGNETIC-RESONANCE SPECTROSCOPY; PSEUDOMONAS EXOTOXIN-A; RECEPTOR GAMMA-CHAIN; STIMULATORY FACTOR-I; PROLIFERATIVE ACTIVITY; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; CARCINOMA-CELLS; FUSION PROTEIN AB Fusion of a ligand to another protein frequently impairs the binding of the ligand. Recombinant toxins composed of mutants of Pseudomonas exotoxin (PE) fused to the C-terminus of human interleukin 4 (IL4) are cytotoxic to IL4 receptor- (IL4R-) bearing tumor cells but bind to the IL4R with only 1% the affinity of IL4. We have developed a method to connect a toxin to a ligand which allows the junction to be moved to a location on the ligand which would minimize the binding impairment. We designed mutants of IL4 in which residue 28, 38, 68, 70, 97, or 105 was substituted with cysteine. All purified mutants bound to the IL4R with 60-100% the affinity of IL4, indicating that the IL4 structure was essentially unchanged. The IL4 mutants were then each conjugated through a disulfide bond to PE35, a truncated form of PE which contains a single cysteine. IL4 conjugated to PE35 at residue 28, 38, or 105 of IL4 bound with 10-fold improved affinity and was 10-fold more cytotoxic than the recombinant IL4-toxin in which PE is fused to position 129 at the C-terminus of IL4. IL4 containing PE35 conjugated at position 68, 70, or 97 had lower binding affinity and cytotoxic activity. These results indicate that the location of the ligand-protein junction can be selectively moved to enhance conjugate effectiveness, and implications could be made regarding which regions of IL4 are important for binding. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. US FDA,NIH,CTR BIOL EVALUAT & RES,DIV CELLULAR GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NR 48 TC 15 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 27 PY 1994 VL 33 IS 38 BP 11637 EP 11644 DI 10.1021/bi00204a027 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PJ293 UT WOS:A1994PJ29300027 PM 7918378 ER PT J AU FURTH, PA STONGE, L BOGER, H GRUSS, P GOSSEN, M KISTNER, A BUJARD, H HENNIGHAUSEN, L AF FURTH, PA STONGE, L BOGER, H GRUSS, P GOSSEN, M KISTNER, A BUJARD, H HENNIGHAUSEN, L TI TEMPORAL CONTROL OF GENE-EXPRESSION IN TRANSGENIC MICE BY A TETRACYCLINE-RESPONSIVE PROMOTER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTORS; EUKARYOTIC CELLS; FUSION GENES; ELEMENTS; ENHANCER; ANIMALS; INT-2 AB Promoters whose temporal activity can be directly manipulated in transgenic animals provide a tool for the study of gene functions in vivo, We have evaluated a tetracycline-responsive binary system for its ability to temporally control gene expression in transgenic mice. In this system, a tetracycline-controlled trans-activator protein (tTA), composed of the repressor of the tetracycline-resistance operon (tet from Escherichia coli transposon Tn10) and the activating domain of viral protein VP16 of herpes simplex virus, induces transcription from a minimal promoter (P-hCMV*-1; see below) fused to seven tet operator sequences in the absence of tetracycline but not in its presence. Transgenic mice were generated that carried either a luciferase or a beta-galactosidase reporter gene under the control of P-hCMV*-1 Or a transgene containing the tTA coding sequence under the control of the human cytomegalovirus immediate early gene 1 (hCMV IE1) promoter/enhancer, Whereas little luciferase or beta-galactosidase activity was observed in tissues of mice carrying only the reporter genes, the presence of tTA in double-transgenic mice induced expression of the reporter genes up to several thousand-fold, This induction was abrogated to basal levels upon administration of tetracycline. These findings can be used, for example, to design dominant gain-of-function experiments in which temporal control of transgene expression is required. C1 MAX PLANCK INST BIOPHYS CHEM, DEPT MOLEC CELL BIOL, D-37018 GOTTINGEN, GERMANY. UNIV MARYLAND, SCH MED, DEPT MED, DIV INFECT DIS, BALTIMORE, MD 21201 USA. UNIV HEIDELBERG, ZENTRUM MOLEK BIOL, D-69120 HEIDELBERG, GERMANY. NIDDKD, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA. RI Gossen, Manfred/K-9602-2013 NR 28 TC 598 Z9 614 U1 3 U2 10 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 SEP 27 PY 1994 VL 91 IS 20 BP 9302 EP 9306 DI 10.1073/pnas.91.20.9302 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800023 PM 7937760 ER PT J AU POLLARD, JW HENNIGHAUSEN, L AF POLLARD, JW HENNIGHAUSEN, L TI COLONY-STIMULATING FACTOR-1 IS REQUIRED FOR MAMMARY-GLAND DEVELOPMENT DURING PREGNANCY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE OSTEOPETROTIC MOUSE; OP; BRANCHING MORPHOGENESIS ID MILK PROTEIN GENE; FACTOR-I CSF-1; OP OP MOUSE; GROWTH-FACTOR; PLACENTAL DEVELOPMENT; ALVEOLAR DEVELOPMENT; HUMAN UTERUS; EXPRESSION; RECEPTOR; OSTEOPETROSIS AB The study of colony stimulating factor 1 (CSF-1), a homodimeric serum growth factor that regulates mononuclear phagocytes and is involved in maternal-fetal interactions during pregnancy, was dramatically enhanced by the observation that the recessive mutation osteopetrosis, op, is an inactivating mutation in the CSF-1-encoding gene. Homozygous mutant (op/op) mice completely lack CSF-1, are osteopetrotic consequent to a deficiency in osteoclasts, have severely reduced numbers of macrophages, and have reduced fertility evident at the pre- and postimplantation stages of pregnancy. We show here that op/op females have a lactational defect, and consequently, although some are able to produce offspring, few nurture any pups and none feeds a full litter. This lactational defect is due to incomplete mammary gland ductal growth during pregnancy, a precocious development of the lobulo-alveolar system, and despite expression of milk proteins, a failure to switch to a lactational state. These data show that CSF-1 has a role in the development of the mammary gland during pregnancy. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT OBSTET & GYNECOL, BRONX, NY 10461 USA. NIDDKD, DEV BIOL SECT, BETHESDA, MD 20892 USA. RP POLLARD, JW (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT DEV & MOLEC BIOL, 1300 MORRIS PK AVE, BRONX, NY 10461 USA. FU NCI NIH HHS [P30-CA13330] NR 30 TC 116 Z9 116 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 SEP 27 PY 1994 VL 91 IS 20 BP 9312 EP 9316 DI 10.1073/pnas.91.20.9312 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800025 PM 7937762 ER PT J AU TSUJI, S QURESHI, MA HOU, EW FITCH, WM LI, SSL AF TSUJI, S QURESHI, MA HOU, EW FITCH, WM LI, SSL TI EVOLUTIONARY RELATIONSHIPS OF LACTATE-DEHYDROGENASES (LDHS) FROM MAMMALS, BIRDS, AN AMPHIBIAN, FISH, BARLEY, AND BACTERIA - LDH CDNA SEQUENCES FROM XENOPUS, PIG, AND RAT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMINO-ACID-SEQUENCE; COMPLETE NUCLEOTIDE-SEQUENCE; A ISOZYME; PROTEIN SEQUENCES; B HEART; GENE; MOUSE; MUSCLE; CLONING; TESTIS AB The nucleotide sequences of the cDNAs encoding LDH (EC 1.1.1.27) subunits LDH-A (muscle), LDH-B (liver), and LDH-C (oocyte) from Xenopus laevis, LDH-A (muscle) and LDH-B (heart) from pig, and LDH-B (heart) and LDH-C (testis) from rat were determined. These seven newly deduced amino acid sequences and 22 other published LDH sequences, and three unpublished fish LDH-A sequences kindly provided by G. N. Somero and D. A. Powers, were used to construct the most parsimonious phylogenetic tree of these 32 LDH subunits from mammals, birds, an amphibian, fish, barley, and bacteria. There have been at least six LDH gene duplications among the vertebrates. The Xenopus LDH-A, LDH-B, and LDH-C subunits are most closely related to each other and then are more closely related to vertebrate LDH-B than LDH-A. Three fish LDH-As, as well as a single LDH of lamprey, also seem to be more related to vertebrate LDH-B than to land vertebrate LDH-A. The mammalian LDH-C (testis) subunit appears to have diverged very early, prior to the divergence of vertebrate LDH-A and LDH-B subunits, as reported previously. C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. UNIV CALIF IRVINE,SCH BIOL SCI,DEPT ECOL & EVOLUTIONARY BIOL,IRVINE,CA 92717. NR 43 TC 54 Z9 67 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 1994 VL 91 IS 20 BP 9392 EP 9396 DI 10.1073/pnas.91.20.9392 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800041 PM 7937776 ER PT J AU YANG, CW VLASSARA, H PETEN, EP HE, CJ STRIKER, GE STRIKER, LJ AF YANG, CW VLASSARA, H PETEN, EP HE, CJ STRIKER, GE STRIKER, LJ TI ADVANCED GLYCATION END-PRODUCTS UP-REGULATE GENE-EXPRESSION FOUND IN DIABETIC GLOMERULAR-DISEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DIABETES MELLITUS; COMPETITIVE PCR; EXTRACELLULAR MATRIX; GROWTH FACTOR; AMINOGUANIDINE ID GLUCOSE-MODIFIED PROTEINS; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; MESSENGER-RNA; HUMAN GLOMERULOSCLEROSIS; MESANGIAL CELLS; TRANSGENIC MICE; NEPHROPATHY; TISSUE; AMINOGUANIDINE AB Several lines of evidence suggest that the excessive accumulation of extracellular matrix in the glomeruli of diabetic kidneys may be due to reactive intermediates forming between glucose and matrix proteins called advanced glycation end products (AGEs). Normal mice received AGE-modified mouse serum albumin i.p. for 4 weeks, and glomerular extracellular matrix, growth factor mRNA levels, and morphology were examined. We found that AGE induced an increase in glomerular extracellular matrix alpha 1(IV) collagen, laminin B1, and transforming growth factor beta(1) mRNA levels, as measured by competitive PCR, as well as glomerular hypertrophy. The AGE response was specific because the coadministration of an AGE inhibitor, aminoguanidine, reduced all these changes. We conclude that AGEs affected expression of genes implicated in diabetic kidney disease and may play a major role in nephropathy. C1 NIDDKD, METAB DIS BRANCH, RENAL CELL BIOL SECT, BETHESDA, MD 20892 USA. PICOWER INST MED RES, MANHASSET, NY 11030 USA. FU NIA NIH HHS [5 RO1 AGO9453-04, R01 AGO6943-07] NR 40 TC 254 Z9 264 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 SEP 27 PY 1994 VL 91 IS 20 BP 9436 EP 9440 DI 10.1073/pnas.91.20.9436 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800050 PM 7937785 ER PT J AU TOPALIAN, SL RIVOLTINI, L MANCINI, M MARKUS, NR ROBBINS, PF KAWAKAMI, Y ROSENBERG, SA AF TOPALIAN, SL RIVOLTINI, L MANCINI, M MARKUS, NR ROBBINS, PF KAWAKAMI, Y ROSENBERG, SA TI HUMAN CD4+ T-CELLS SPECIFICALLY RECOGNIZE A SHARED MELANOMA-ASSOCIATED ANTIGEN ENCODED BY THE TYROSINASE GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CULTURED HUMAN MELANOCYTES; EXPRESSION; CLONES; HLA; IDENTIFICATION; CD4+; CTL; IMMUNOSELECTION; IMMUNOTHERAPY AB Although commonly expressed human melanoma-associated antigens recognized by CD8(+) cytolytic T cells have been described, little is known about CD4(+) T-cell recognition of melanoma-associated antigens. Epstein-Barr virus-transformed B cells were used to present antigens derived from whole cell lysates of autologous and allogeneic melanomas for recognition by melanoma-specific CD4(+) T-cell lines and clones cultured from tumor-infiltrating lymphocytes. HLA-DR-restricted antigens were detected in the lysates on the basis of specific release of cytokines from the responding T cells. Antigen sharing was demonstrated in the majority of melanomas tested, as well as in cultured normal melanocytes, but not in other normal tissues or nonmelanoma tumors. T-cell clones manifested a single recognition pattern, suggesting the presence of an immunodominant epitope. This epitope was identified as a product of the tyrosinase gene, which has also been shown to encode class I-restricted epitopes recognized by CD8(+) T cells from melanoma patients. Identification of commonly expressed tumor-associated protein molecules containing epitopes presented by both class I and class II major histocompatibility molecules may provide optimal reagents for cancer immunization strategies. RP TOPALIAN, SL (reprint author), NCI,SURG BRANCH,10-2B47,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini, Licia/0000-0002-2409-6225 NR 42 TC 239 Z9 241 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 1994 VL 91 IS 20 BP 9461 EP 9465 DI 10.1073/pnas.91.20.9461 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800055 PM 7937789 ER PT J AU OCONNOR, PM FERRIS, DK HOFFMANN, I JACKMAN, J DRAETTA, G KOHN, KW AF OCONNOR, PM FERRIS, DK HOFFMANN, I JACKMAN, J DRAETTA, G KOHN, KW TI ROLE OF THE CDC25C PHOSPHATASE IN G(2) ARREST INDUCED BY NITROGEN-MUSTARD SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL CYCLE; CHECKPOINTS; CDC2 KINASE; DNA DAMAGE ID CELL-CYCLE; PROTEIN PHOSPHATASE; KINASE; PHOSPHORYLATION; MITOSIS; CHECKPOINTS; INVOLVEMENT; ACTIVATION; P34CDC2; G2 AB G(2) arrest induced by nitrogen mustard in human lymphoma CA46 cells is associated with a failure to activate hyperphosphorylated cdc2/cyclin B1 complexes. We investigated the possibility that this might be due to a suppression of cdc25C phosphatase activity. cdc25C from interphase cells migrated as a 54- to 57-kDa doublet in SDS gels and exhibited basal phosphatase activity. cdc25C from mitotic cells migrated as a 66-kDa hyperphosphorylated species and exhibited elevated phosphatase activity. cdc25C hyperphosphorylation and activation were mediated by cdc2, supporting the view of a cdc2-cdc25C autocatalytic feedback loop. Immunofluorescence and cell fractionation studies suggested cdc2-cdc25C interaction occurred within the cytoplasm. Cells arrested in G(2) phase following nitrogen mustard treatment or cells arrested in S phase with aphidicolin failed to dephosphorylate and activate cdc2, and this correlated with failure to convert cdc25C into the most active hyperphosphorylated species. Our findings suggest that checkpoints guarding against mitotic entry in the presence of unreplicated or damaged DNA suppress formation of the cdc2-cdc25C autocatalytic feedback loop that normally brings about rapid activation of cdc2. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. EUROPEAN MOLEC BIOL LAB,CELL BIOL PROGRAM,D-69012 HEIDELBERG,GERMANY. MITOTIX,CAMBRIDGE,MA 02139. RP OCONNOR, PM (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 26 TC 97 Z9 97 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 1994 VL 91 IS 20 BP 9480 EP 9484 DI 10.1073/pnas.91.20.9480 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800059 PM 7937793 ER PT J AU XIAO, RP CHENG, HP LEDERER, WJ SUZUKI, T LAKATTA, EG AF XIAO, RP CHENG, HP LEDERER, WJ SUZUKI, T LAKATTA, EG TI DUAL REGULATION OF CA2+/CALMODULIN-DEPENDENT KINASE-II ACTIVITY BY MEMBRANE VOLTAGE AND BY CALCIUM INFLUX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AUTOPHOSPHORYLATION; CALCIUM CHANNEL FACILITATION; HEART CELLS; CONFOCAL MICROSCOPY ID DEPENDENT PROTEIN-KINASE; SARCOPLASMIC-RETICULUM; MAMMALIAN HEART; CYTOSOLIC CA2+; PHOSPHORYLATION; POTENTIATION; CHANNEL; MUSCLE; CELLS; AUTOPHOSPHORYLATION AB Calcium entry through voltage-gated Ca2+ channels is critical in cardiac excitation-contraction coupling and calcium metabolism. In this report, we demonstrate both spatially resolved and temporally distinct effects of Ca2+/ calmodulin-dependent protein kinase II (CaMKII) on L-type Ca2+ channel current (I-Ca) in rat cardiac myocytes. Either depolarization alone or calcium influx can increase the amplitude and slow the inactivation of I-Ca. The distinct voltage- and Ca2+-dependent effects persist with time constants of approximate to 1.7 sec and 9 sec, respectively. Both effects are completely abolished by a specific peptide inhibitor of CaMKII. This CaMKII inhibitor also suppresses the prolongation of I-Ca induced by depolarizing holding potentials. Furthermore, using an antibody specific for the autophosphorylated (activated) CaMKII, we find that this kinase is localized close to sarcolemmal membranes and that the profile of CaMKII activation correlates qualitatively with the changes in I-Ca under various conditions. Therefore, we conclude that the action of CaMKII on I-Ca is dually regulated by membrane depolarization and by Ca2+ influx; the latter directly activates CaMKII, whereas the former likely promotes the interaction between constitutive CaMKII and the membrane-channel proteins. These regulatory mechanisms provide positive-feedback control of Ca2+ channels and are probably important in the regulation of cardiac contractility and other intracellular Ca2+-regulated processes. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. NAGOYA CITY UNIV,SCH MED,DEPT BIOCHEM,MIZUHO KU,NAGOYA,AICHI 467,JAPAN. RI Lederer, William/B-1285-2010 NR 24 TC 155 Z9 157 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 1994 VL 91 IS 20 BP 9659 EP 9663 DI 10.1073/pnas.91.20.9659 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800096 PM 7937825 ER PT J AU FIEDLER, JL EPSTEIN, CJ RAPOPORT, SI CAVIEDES, R CAVIEDES, P AF FIEDLER, JL EPSTEIN, CJ RAPOPORT, SI CAVIEDES, R CAVIEDES, P TI REGIONAL ALTERATION OF CHOLINERGIC FUNCTION IN CENTRAL NEURONS OF TRISOMY-16 MOUSE FETUSES, AN ANIMAL-MODEL OF HUMAN TRISOMY-21 (DOWN-SYNDROME) SO BRAIN RESEARCH LA English DT Article DE ACETYLCHOLINE; TRISOMY; NERVOUS SYSTEM ID DORSAL-ROOT GANGLION; NERVE GROWTH-FACTOR; ELECTRICAL MEMBRANE-PROPERTIES; EMBRYONIC BRAIN-DEVELOPMENT; DOWNS-SYNDROME; BASAL FOREBRAIN; ALZHEIMERS-DISEASE; SPINAL-CORD; MICE; ABNORMALITIES AB The trisomy-16 (TS16) mouse is considered to be a model of human trisomy 21 (Down syndrome) because of genetic homology between mouse chromosome 16 and human chromosome 21. We examined cholinergic function of brain and spinal cord tissue and in cultured neurons from TS16 mouse compared with that of age matched controls. Mean acetylcholinesterase activity in both tissue types did not differ between trisomic and control conditions. Acetylcholine (ACh) synthesis, measured as choline O-acetyltratransferase (acetyl-CoA) activity, was reduced to 67% of control in TS16 brain but not in TS16 spinal cord. Steady-state accumulation of ACh precursor, [H-3]choline, was measured in primary cell cultures. Steady-state choline uptake was reduced to 35% and to 61% in neurons of TS16 brain and spinal cord, respectively, when compared with controls. Kinetics experiments in TS16 brain cells showed a 50% reduction of the maximal velocity of choline uptake when compared to controls. Further, the ACh release induced by KCl depolarization in TS16 spinal card neurons did not differ from control neurons but was reduced in TS16 brain neurons. This effect cannot be explained solely by a reduction in ACh synthesis. The results indicate that the TS16 condition in mice significantly modified the cholinergic function in brain, and to a lesser degree in spinal cord, suggesting that the higher gene dosage inherent to the trisomic condition affects cholinergic neurons in different regions of the central nervous system in a differential fashion. C1 UNIV CHILE,FAC MED,DEPT FIS & BIOFIS,CASILLA 70005,CHILE. CTR ESTUDIOS CIENT SANTIAGO,CASILLA 16443,CHILE. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP FIEDLER, JL (reprint author), UNIV CHILE,FAC MED,DEPT BIOQUIM & QUIM,CORREO 7,CASILLA 70086,CHILE. RI Fiedler, Jenny/I-5617-2016 NR 38 TC 30 Z9 30 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 SEP 26 PY 1994 VL 658 IS 1-2 BP 27 EP 32 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PH002 UT WOS:A1994PH00200005 PM 7834352 ER PT J AU MCMILLIAN, MK MULLIS, SB WU, GC HUDSON, PM PENNYPACKER, KR HONG, JS AF MCMILLIAN, MK MULLIS, SB WU, GC HUDSON, PM PENNYPACKER, KR HONG, JS TI REGULATION OF TYROSINE-HYDROXYLASE IN OLFACTORY-BULB CULTURES - SELECTIVE-INHIBITION OF DEPOLARIZATION-INDUCED INCREASE BY ENDOGENOUS OPIOIDS SO BRAIN RESEARCH LA English DT Article DE TYROSINE HYDROXYLASE; OLFACTORY BULB; DOPAMINE; ENKEPHALIN; NEURONAL CULTURE; NALOXONE; NIMODIPINE ID ADRENAL CHROMAFFIN CELLS; GENE-RELATED PEPTIDE; NERVE GROWTH-FACTOR; DOPAMINE RELEASE; NARIS CLOSURE; MESSENGER-RNA; EXPRESSION; NEURONS; SYSTEM; ACTIVATION AB Regulation of tyrosine hydroxylase (TH) by second messenger pathway activators was examined in rat olfactory bulb cell cultures. The number of TH-immunoreactive neurons was increased 2-3-fold by 36 h treatments with forskolin (Fsk, 10(-6) M) or phorbol myristate acetate (PMA, 10(-7) M), but was not significantly increased by a depolarizing concentration of KCl (45 mM). In contrast, KCl increased media [Met(5)]enkephalin (ME) immunoreactivity 2-fold in these cultures, equivalent to stimulation with Fsk or PMA. The possibility was examined that ME or another opioid produced by the cultures selectively inhibited the TH response to KCl. Pretreatment with the opioid receptor antagonist naloxone (10(-6) M) greatly increased the number of TR-immunoreactive neurons observed in response to KCl treatment, but had no effect on basal or Fsk-stimulated TH immunostaining, nor on basal or stimulated ME release. The increase in TH-immunoreactivity observed with combined KCl plus naloxone treatment was prevented by pretreating the cultures with the calcium channel blocker nimodipine (10(-6) M), which had no effect on Fsk stimulation or basal TH immunostaining. These data suggest that endogenous opioids selectively inhibit KCl-stimulated Ca2+ entry and thus TH induction in olfactory bulb cell cultures. These cultures offer a simple model system for further study of TH regulation in dopaminergic neurons. RP MCMILLIAN, MK (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,MD E1-01,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 30 TC 20 Z9 21 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 SEP 26 PY 1994 VL 658 IS 1-2 BP 105 EP 111 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PH002 UT WOS:A1994PH00200014 PM 7834330 ER PT J AU KIRKPATRICK, B KIM, JW INSEL, TR AF KIRKPATRICK, B KIM, JW INSEL, TR TI LIMBIC SYSTEM FOS EXPRESSION ASSOCIATED WITH PATERNAL BEHAVIOR SO BRAIN RESEARCH LA English DT Article DE PATERNAL BEHAVIOR; MATERNAL BEHAVIOR; MICROTUS, AMYGDALA; FOS ID BIPARENTAL CALIFORNIA MOUSE; FEMALE PRAIRIE VOLES; MATERNAL-BEHAVIOR; PEROMYSCUS-CALIFORNICUS; MICROTUS-OCHROGASTER; SUBSTANTIA INNOMINATA; MEDIAL AMYGDALA; PREOPTIC AREA; LESIONS; RATS AB Axon-sparing lesions of the medial nucleus of the amygdala (MeA) decrease male parental behavior in the highly social prairie vole. To assess further the role of the amygdala in paternal behavior, male and female prairie voles were exposed to a pup or a non-social olfactory stimulus for 3 hours, and cells expressing Fos peptide were labelled using immunocytochemistry. Compared to controls, males exposed to a pup showed an increase in Fos expression in the MeA, as well as in several areas with connections to it: the accessory olfactory bulb, lateral septum, medial preoptic area, medial bed nucleus of the stria terminalis, nucleus reuniens and paraventricular nucleus of the thalamus. There was no increase in Fos immunoreactivity in the paraventricular nucleus of the hypothalamus or piriform cortex. The same pattern of Fos expression was found in female voles, with the exception of the thalamic paraventricular nucleus, where there was an increase in the pup-exposed group that was not statistically significant (P = 0.11). In addition, the magnitude of induction in females was markedly less than that in males in the medial preoptic area. These results provide further evidence that the MeA is involved in paternal behavior, and suggest certain other areas previously implicated in maternal behavior may also be involved in the control of paternal behavior in this species. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD. RP KIRKPATRICK, B (reprint author), UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,POB 21247,CATONSVILLE,MD 21228, USA. FU NIMH NIH HHS [MH-00925, MH-40279] NR 51 TC 73 Z9 73 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 26 PY 1994 VL 658 IS 1-2 BP 112 EP 118 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PH002 UT WOS:A1994PH00200015 PM 7834331 ER PT J AU VISWANATHAN, M DEOLIVEIRA, AM CORREA, FMA SAAVEDRA, JM AF VISWANATHAN, M DEOLIVEIRA, AM CORREA, FMA SAAVEDRA, JM TI EXPRESSION OF A NOVEL NON-ANGIOTENSIN-II [I-125] CGP-42112 BINDING-SITE IN HEALING WOUNDS OF THE RAT-BRAIN SO BRAIN RESEARCH LA English DT Note DE BRAIN INJURY; MICROGLIA; MACROPHAGE; CGP 42112; WOUND HEALING; INFLAMMATION ID MONONUCLEAR PHAGOCYTES; MAMMALIAN BRAIN; RECEPTORS; MICROGLIA; ASSOCIATION; INHIBITION; CGP-42112A; DISEASE; INJURY; SKIN AB We characterized a novel non-angiotensin II binding site that is recognized by the angiotensin II AT(2) receptor ligand [I-125]CGP 42112, in healing brain wounds of adult rats. The binding, which was highest at 3 days after injury, appears to be localized to activated microglia surrounding the wound. The novel CGP 42112 binding site may have a role in the function of microglia and in mechanisms of tissue repair in the brain. RP VISWANATHAN, M (reprint author), NIMH,PHARMACOL SECT,CLIN SCI LAB,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 28 TC 26 Z9 26 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 SEP 26 PY 1994 VL 658 IS 1-2 BP 265 EP 270 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PH002 UT WOS:A1994PH00200034 PM 7834351 ER PT J AU GARRAFFO, HM SIMON, LD DALY, JW SPANDE, TF JONES, TH AF GARRAFFO, HM SIMON, LD DALY, JW SPANDE, TF JONES, TH TI CIS-CONFIGURATIONS AND TRANS-CONFIGURATIONS OF ALPHA,ALPHA'-DISUBSTITUTED PIPERIDINES AND PYRROLIDINES BY GC-FTIR - APPLICATION TO DECAHYDROQUINOLINE STEREOCHEMISTRY SO TETRAHEDRON LA English DT Article ID ALKALOIDS; VENOM; MONOMORIUM; ANT; SOLENOPSIS; CHEMISTRY AB GC-FTIR spectroscopy provides a convenient, rapid method to distinguish cis- and trans-alpha,alpha'-disubstituted piperidines and pyrrolidines; the pyrrolidines usually first require N-methylation. Cis-isomers exhibit significant Bohlmann bands, transisomers only very weak bands. The method is also applicable to alkaloids containing a piperidine ring. For example, a 2-propyl-5-methyldecahydroquinoline, named trans-195A, recently detected in skin extracts of a dendrobatid frog is shown by GC-FTIR to have C(2) and C(8a) in a cis-orientation, C1 VIRGINIA MIL INST,DEPT CHEM,LEXINGTON,VA 24450. RP GARRAFFO, HM (reprint author), NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 17 TC 21 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD SEP 26 PY 1994 VL 50 IS 39 BP 11329 EP 11338 PG 10 WC Chemistry, Organic SC Chemistry GA PH432 UT WOS:A1994PH43200001 ER PT J AU LE, SY PATTABIRAMAN, N MAIZEL, JV AF LE, SY PATTABIRAMAN, N MAIZEL, JV TI RNA TERTIARY STRUCTURE OF THE HIV RRE DOMAIN-II CONTAINING NON-WATSON-CRICK BASE-PAIRS GG AND GA - MOLECULAR MODELING STUDIES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHENYLALANINE TRANSFER-RNA; REV-RESPONSE ELEMENT; TARGET SEQUENCE; VIRAL-RNA; PROTEIN; BINDING; RECOGNITION; EXPRESSION; ACTIVATOR AB We have used molecular modeling techniques to model the RNA tertiary structure of the viral RNA element (referred to as domain II of Rev responsive element, RRE) bound by the Rev protein of HIV. In this study, the initial three-dimensional model was built from its established RNA secondary structure, including three non-Watson-Crick G:G, G:A and G:U base pairs. Molecular dynamics (MD) simulations were performed with hydrated or unhydrated sodium ions. Our results indicate that the non-Watson-Crick base pairs in the simulation with unhydrated sodium ions and water are more stable than those with hydrated sodium ions only. The RNA can maintain its compact double helical structure throughout the course of the MD simulations with water and unhydrated sodium ions, although the non-Watson-Crick base pairs and two bulge loops show much more flexibility and conformational distortion than the classical RNA helical region. The distinct distortion of the sugar-phosphate backbone significantly widens the RNA major groove so that the major groove is readily accessible for hydrogen bonding by specific Rev binding. This model emphasizes the importance of specific hydrogen bonding in the stabilization of the three-dimensional structure of the HIV Rev core binding element, not only between the nucleotide bases, but also among the ribose hydroxyls, phosphate anionic oxygens, base oxygens and nitrogens, and bridging water molecules. Moreover, our results suggest that sodium ions play an important role in the formation of base pairs G:G and G:A of the RRE by a manner similar to the arginine of the Rev-RRE complex. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. RP LE, SY (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,FREDERICK,MD 21702, USA. NR 44 TC 11 Z9 11 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 25 PY 1994 VL 22 IS 19 BP 3966 EP 3976 DI 10.1093/nar/22.19.3966 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK953 UT WOS:A1994PK95300023 PM 7937119 ER PT J AU GAUSE, GG GONDA, MA AF GAUSE, GG GONDA, MA TI SOLID-PHASE ASSAYS FOR THE DETECTION OF INHIBITORS OF HIV REVERSE-TRANSCRIPTASE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP GAUSE, GG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,POB B,FREDERICK,MD 21702, USA. NR 5 TC 1 Z9 2 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 SEP 25 PY 1994 VL 22 IS 19 BP 4018 EP 4019 DI 10.1093/nar/22.19.4018 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK953 UT WOS:A1994PK95300031 PM 7524032 ER PT J AU EVANS, GA GARCIA, GG ERWIN, R HOWARD, OMZ FARRAR, WL AF EVANS, GA GARCIA, GG ERWIN, R HOWARD, OMZ FARRAR, WL TI PERVANADATE SIMULATES THE EFFECTS OF INTERLEUKIN-2 (IL-2) IN HUMAN T-CELLS AND PROVIDES EVIDENCE FOR THE ACTIVATION OF 2 DISTINCT TYROSINE KINASE PATHWAYS BY IL-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P70-75 BETA-SUBUNIT; SIGNAL TRANSDUCTION; RECEPTOR COMPLEX; PROTEIN-KINASE; LYMPHOCYTES-T; PHOSPHORYLATION; ASSOCIATION AB Pervanadate has been shown to rapidly increase the level of tyrosine phosphorylation in intact cells. Because one of the most rapidly detectable events following treatment of human T cells with interleukin-2 (IL-2) is tyrosine kinase activation, we were interested to determine whether pervanadate could act to induce IL-2-associated events. We show here that pervanadate does act to induce IL-2 signal transduction pathways as determined by induction of mitogenesis and interferon gamma production in normal human T cells and the factor independent T cell line YT. Analysis of signal transduction events shows that pervanadate induces the activity of the src family of tyrosine kinases lck and fyn and the tyrosine phosphorylation of a major IL-2 responsive protein of 97 kDa. Pervanadate does not, however, induce the activity of tyrosine kinases associated with the IL-2 receptor or the phosphorylation of a major IL-2 responsive protein of 116 kDa (Jak-3). Together these data suggest that src family kinase activation is a down stream event following IL-2 stimulation and is not directly associated with the activation of the IL-2 receptor-associated tyrosine kinase. The data also imply that tyrosine phosphorylation of p116/Jak-3 is strictly associated with activation of tyrosine kinases associated with the IL-2 receptor. With the use of pervanadate as a tool, we have established a dissociation of src family kinases with IL-2 receptor activation and imply the involvement of two distinct tyrosine kinase pathways, a receptor-associated pathway closely coupled with Jak-3 phosphorylation and a downstream pathway involving src family kinase activation. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, CYTOKINE MECHANISMS SECT, FREDERICK, MD 21702 USA. RP EVANS, GA (reprint author), NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 29 TC 45 Z9 45 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 SEP 23 PY 1994 VL 269 IS 38 BP 23407 EP 23412 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ345 UT WOS:A1994PQ34500007 PM 8089104 ER PT J AU PAPP, PP MUKHOPADHYAY, G CHATTORAJ, DK AF PAPP, PP MUKHOPADHYAY, G CHATTORAJ, DK TI NEGATIVE CONTROL OF PLASMID DNA-REPLICATION BY ITERONS - CORRELATION WITH INITIATOR BINDING-AFFINITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SHOCK PROTEINS DNAJ; P1-PLASMID REPLICATION; P1 REPLICATION; REPA PROTEIN; ORIGIN; SEQUESTRATION; SEQUENCES; GENE AB Initiation of DNA replication and negative control of initiation frequency in many bacterial plasmids are mediated by multiple binding sites (iterons) for the replicon-encoded initiator protein. Here we show that a single iteron of plasmid P1, when cloned in a multicopy vector, pUC19, can control replication of a miniP1 plasmid effectively. Using this assay system, several iterons with single point mutations were analyzed. The degree of control was directly correlated with the binding affinity of the iterons for the initiator protein in vitro. The control was also unaffected whether or not a wild type iteron was flanked with strong transcription terminators. We conclude that initiator binding is the only activity of p1 iteron sequences relevant to replication control. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Papp, Peter/A-6907-2013 NR 25 TC 25 Z9 25 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 SEP 23 PY 1994 VL 269 IS 38 BP 23563 EP 23568 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ345 UT WOS:A1994PQ34500029 PM 8089124 ER PT J AU OTSUKA, F IWAMATSU, A SUZUKI, K OHSAWA, M HAMER, DH KOIZUMI, S AF OTSUKA, F IWAMATSU, A SUZUKI, K OHSAWA, M HAMER, DH KOIZUMI, S TI PURIFICATION AND CHARACTERIZATION OF A PROTEIN THAT BINDS TO METAL-RESPONSIVE ELEMENTS OF THE HUMAN METALLOTHIONEIN II(A) GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR FACTOR; TRANSCRIPTION FACTOR; REGULATORY ELEMENTS; I PROMOTER; DEPENDENT BINDING; IIA GENE; ENCODING METALLOTHIONEIN; GEL-ELECTROPHORESIS; HEAVY-METALS; INTERACTS AB Metal responsive element (MRE) is a cis-acting DNA motif located in the upstream region of vertebrate metallothionein genes, which can confer metal responsiveness on downstream heterologous promoters. A protein that binds to the MRE sequence in a zinc-dependent manner (zinc regulatory factor; ZRF) was purified 16,000-fold from HeLa cell nuclear extracts by means of the avidin-biotin method, in which a complex formed between ZRF and a biotinylated probe containing MRE was trapped by streptavidin-agarose beads, and ZRF was recovered by salt extraction. By repeating the method three times, a homogeneous 116-kDa protein was obtained whose recovery was zinc-dependent and MRE sequence-specific. UV cross-linking analysis also revealed that a protein that specifically binds to MRE has the same molecular mass as the purified protein. Zinc-dependent and MRE sequence-specific footprints of ZRF were obtained on MREa and MREb in the upstream region of the human metallothionein IIA, gene. The ZRF MRE complex dissociates by the addition of chelating reagents, suggesting a direct role of zinc ions in the DNA binding of ZRF. Partial amino acid sequences of ZRF were found to be highly homologous to those of a mouse MRE-binding protein, mMTF-1. C1 KIRIN BREWERY CO LTD,CENT LABS KEY TECHNOL,YOKOHAMA,KANAGAWA 236,JAPAN. NATL INST IND HLTH,DEPT EXPTL TOXICOL,KAWASAKI,KANAGAWA 214,JAPAN. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP OTSUKA, F (reprint author), TEIKYO UNIV,FAC PHARMACEUT SCI,DEPT ENVIRONM TOXICOL,SAGAMIKO,KANAGAWA 19901,JAPAN. NR 45 TC 62 Z9 62 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 23 PY 1994 VL 269 IS 38 BP 23700 EP 23707 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ345 UT WOS:A1994PQ34500049 PM 8089141 ER PT J AU TAKAGI, Y SHRIVASTAV, S MIKI, T SAKAGUCHI, K AF TAKAGI, Y SHRIVASTAV, S MIKI, T SAKAGUCHI, K TI MOLECULAR-CLONING AND EXPRESSION OF THE ACIDIC FIBROBLAST GROWTH-FACTOR RECEPTORS IN A RAT PARATHYROID CELL-LINE (PT-R) - PARATHYROID CELL-SPECIFIC CALCIUM-DEPENDENT CHANGE OF LIGAND ACCESSIBILITY AND COVALENT ATTACHMENT OF HEPARAN-SULFATE GLYCOSAMINOGLYCAN TO THE RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CDNA CLONING; SYSTEM AB We have previously identified two fibroblast growth factor (FGF) receptors with higher affinity for acidic FGF rather than basic FGF in a rat parathyroid cell line (PT-r). Carbohydrate analyses of the receptors suggested the presence of three different types of FGF receptors, a 150-kDa glycoprotein receptor a similar to 150-kDa heparan sulfate-proteoglycan receptor, and a 130-kDa glycoprotein receptor (Sakaguchi, K., Yanagishita, M., Takeuchi, Y., and Aurbach, G. D. (1991) J. Biol. Chem. 266, 7270-7278). Here, we have cloned two isoforms of the FGF receptors from PT-r cells; one with two immunoglobulin (Ig) like domains (clone a), and the other with an additional Ig-like domain and an acidic box (clone b). They showed highest homology to the mouse and human keratinocyte growth factor receptors among the FGF receptors reported, Clones a and b had one and three possible glycosaminoglycan attachment sites, respectively. Heparitinase treatment of PT-r cells transfected with clone a suggested that the protein for the 150-kDa glycoprotein receptor was encoded by clone a, and that the same protein also served as a core protein for the similar to 150-kDa heparan sulfate proteoglycan receptor. Heparan sulfate glycosaminoglycan attachment to the 150-kDa receptor encoded by clone b was not detectable by the same enzyme treatment. Site-directed mutagenesis (from Ser to Ala) studies of the consensus sequence for the attachment of glycosaminoglycans further supported the presence of covalently attached heparan sulfate glycosaminoglycan in the similar to 150-kDa heparan sulfate proteoglycan receptor. These receptors overexpressed in PT-r cells changed ligand accessibility or apparently translocated after changing extracellular calcium concentrations in a manner similar to the native receptors in PT-r cells (Sakaguchi, K. (1992) J. Biol. Chem. 267, 24554-24562), whereas those expressed in CHO-K1 or NIH/3T3 cells did not. These findings strongly suggest that the two FGF receptor isoforms cloned here represent the acidic FGF receptors that we reported earlier. A subpopulation of the receptors carries heparan sulfate glycosaminoglycan covalently attached to the core protein, and the change in ligand accessibility in response to the shift in ambient calcium concentration is specific to the parathyroid cells. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 12 TC 11 Z9 11 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 23 PY 1994 VL 269 IS 38 BP 23743 EP 23749 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ345 UT WOS:A1994PQ34500055 PM 8089146 ER PT J AU HAGEN, SJ AF HAGEN, SJ TI HANDEDNESS - BASIC PHYSICS SO SCIENCE LA English DT Letter RP HAGEN, SJ (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 23 PY 1994 VL 265 IS 5180 BP 1792 EP 1792 DI 10.1126/science.7993483 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PH258 UT WOS:A1994PH25800008 PM 7993483 ER PT J AU VONLUBITZ, DKJE LIN, RCS POPIK, P CARTER, MF JACOBSON, KA AF VONLUBITZ, DKJE LIN, RCS POPIK, P CARTER, MF JACOBSON, KA TI ADENOSINE A(3) RECEPTOR STIMULATION AND CEREBRAL-ISCHEMIA SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ADENOSINE RECEPTOR; BRAIN ISCHEMIA, THERAPY; CEREBRAL BLOOD FLOW; (GERBIL) ID MOLECULAR-CLONING; FOREBRAIN ISCHEMIA; BLOOD-FLOW; RAT-BRAIN; RESUSCITATION; SEIZURES; GLUCOSE; THERAPY; ARREST; NUMBER AB Chronic treatment with the selective adenosine A(3) receptor agonist N-6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A(1) nor A(2) receptors are involved in these actions. The data indicate that stimulation of adenosine A(3) receptors may play an important role in the development of ischemic damage, and that adenosine A(3) receptors may offer a new target for therapeutic interventions. C1 HAHNEMANN UNIV,DEPT PHYSIOL & BIOPHYS,PHILADELPHIA,PA 19102. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP VONLUBITZ, DKJE (reprint author), NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BLDG 8,RM 111,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009; Popik, Piotr/R-5383-2016 OI Jacobson, Kenneth/0000-0001-8104-1493; Popik, Piotr/0000-0003-0722-1263 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 49 TC 207 Z9 208 U1 0 U2 3 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 SEP 22 PY 1994 VL 263 IS 1-2 BP 59 EP 67 DI 10.1016/0014-2999(94)90523-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ163 UT WOS:A1994PJ16300008 PM 7821362 ER PT J AU HULIHANGIBLIN, BA PARK, YD AULAKH, CS AF HULIHANGIBLIN, BA PARK, YD AULAKH, CS TI DIFFERENTIAL-EFFECTS OF CHRONIC ANTIDEPRESSANT TREATMENT ON 5-HT1C RECEPTOR-BINDING SITES IN WISTAR RAT-BRAIN SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE 5-HT1C RECEPTOR; [H-3] MESULERGINE; CLOMIPRAMINE; IMIPRAMINE; CLORGYLINE; (WISTAR RAT) ID ELECTROCONVULSIVE SHOCK; SEROTONIN RECEPTOR; 8-OH-DPAT; TURNOVER; DRUGS AB The effects of chronic clomipramine, imipramine and clorgyline on 5-HT1C receptors were studied in discrete brain regions, in male Wistar rats, using [H-3]mesulergine to label the receptor binding sites. Clorgyline treatment significantly reduced [H-3]mesulergine binding (B-max values) in both the hypothalamus and striatum compared to saline-treated animals. There were no differences in the maximum number of [H-3]mesulergine binding sites following clorgyline in the hippocampus, frontal cortex or brainstem. Neither clomipramine or imipramine treatment resulted in any significant changes in 5-HT1C receptor number in the brain regions examined here. Furthermore, the K-d Values (receptor affinity) for [H-3]mesulergine binding were not significantly different comparing treatment groups to control animals. The significant changes in discrete brain regions following chlorgyline treatment suggest that 5-HT1C receptors may be involved in the clinical efficacy for the treatment of depression and other neuropsychiatric disorders. C1 NIAAA,CTR CLIN,NEUROGENET LAB,BETHESDA,MD 20892. NIMH,CTR CLIN,CLIN SCI LAB,BETHESDA,MD 20892. RP HULIHANGIBLIN, BA (reprint author), NIAAA,CTR CLIN,NEUROCHEM & NEUROENDOCRINOL SECT,CLIN STUDIES LAB,ROOM 3C-216,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 7 Z9 7 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 SEP 22 PY 1994 VL 263 IS 1-2 BP 213 EP 216 DI 10.1016/0014-2999(94)90545-2 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ163 UT WOS:A1994PJ16300030 PM 7821356 ER PT J AU MOFFETT, JR PALKOVITS, M NAMBOODIRI, MAA NEALE, JH AF MOFFETT, JR PALKOVITS, M NAMBOODIRI, MAA NEALE, JH TI COMPARATIVE DISTRIBUTION OF N-ACETYLASPARTYLGLUTAMATE AND GAD(67) IN THE CEREBELLUM AND PRECEREBELLAR NUCLEI OF THE RAT UTILIZING ENHANCED CARBODIIMIDE FIXATION AND IMMUNOHISTOCHEMISTRY SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NAAG; GLUTAMIC ACID DECARBOXYLASE; MESSY FIBERS; DEEP CEREBELLAR NUCLEI; PONTINE NUCLEI ID ACETYL-ASPARTYL-GLUTAMATE; ACIDIC DIPEPTIDASE ACTIVITY; PARALLEL FIBER TERMINALS; OLFACTORY-BULB; NERVE-TERMINALS; CAT CEREBELLUM; VISUAL-SYSTEM; IMMUNOREACTIVITY; NEURONS; LOCALIZATION AB The most prevalent peptide in the nervous system, N-acetylaspartylglutamate (NAAG), specifically activates N-methyl D-aspartate (NMDA) receptors and a subclass of metabotropic glutamate receptors. One action of this peptide may be to modulate the release of other neurotransmitters, including gamma-aminobutyric acid (GABA). The present study describes the cellular distribution of NAAG, relative to GABA, in the cerebellum and precerebellar nuclei as a foundation for further physiological investigations. Numerous cells of origin for messy fibers, including many of the larger neurons of the pontine nuclei, lateral reticular nuclei, vestibular nuclei, reticulotegmental nuclei, and spinal grey, were moderately to strongly stained for NAAG. Many NAAG-labeled fibers were clearly visible in the cerebellar peduncles and central white matter. Messy fibers and messy endings were among the most prominent NAAG-immunoreactive elements in the cerebellar cortex. Most neurons in the inferior olive were not stained for NAAG, and only sparse, lightly immunoreactive, climbing fiber-like endings could be identified in restricted regions of the cortical molecular layer. Purkinje neurons ranged from nonreactive to moderately positive, with the great majority being unstained. Cerebellar granule cells did not exhibit any NAAG immunoreactivity. A population of neurons in the deep cerebellar nuclei was highly immunoreactive for NAAG. Additionally, many neurons of the red nucleus were intensely stained for NAAG. Comparisons with staining for the 67 kD form of glutamic acid decarboxylase in serial sections revealed complementary distributions, with NAAG in excitatory pathways and cell groups, and glutamic acid decarboxylase in inhibitory systems. These findings suggest a significant functional involvement of NAAG in the excitatory afferent and efferent projection systems and provide an anatomical basis for investigations into the interactions of NAAG and GABA in the cerebellum. (C) 1994 Wiley-Liss, Inc. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP MOFFETT, JR (reprint author), GEORGETOWN UNIV,DEPT BIOL,37TH & O ST NW,WASHINGTON,DC 20057, USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU NEI NIH HHS [EY09085]; NIDA NIH HHS [DA02297] NR 58 TC 24 Z9 24 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 SEP 22 PY 1994 VL 347 IS 4 BP 598 EP 618 DI 10.1002/cne.903470410 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA PF029 UT WOS:A1994PF02900009 PM 7814677 ER PT J AU HELD, PJ KAHAN, BD HUNSICKER, LG LISKA, D WOLFE, RA PORT, FK GAYLIN, DS GARCIA, JR AGODOA, LYC KRAKAUER, H AF HELD, PJ KAHAN, BD HUNSICKER, LG LISKA, D WOLFE, RA PORT, FK GAYLIN, DS GARCIA, JR AGODOA, LYC KRAKAUER, H TI THE IMPACT OF HLA MISMATCHES ON THE SURVIVAL OF FIRST CADAVERIC KIDNEY-TRANSPLANTS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RENAL-TRANSPLANTATION; GRAFT-SURVIVAL; CYCLOSPORINE; RECIPIENTS; EXPERIENCE; THERAPY AB Background. The benefits of HLA-A, B, and DR matching of cadaveric kidney grafts and recipients remain controversial when viewed from the perspective of social equity and graft survival. Methods. We estimated graft survival using proportional-hazards techniques, adjusting for patient and donor characteristics, for a series of 30,564 Medicare patients receiving a first cadaveric kidney transplant between 1984 and 1990. The effects of minimal achievable HLA mismatches and maximal matching on graft survival were estimated by simulated allocation of a sample of organs to a sample of 20,000 candidates for transplantation. Results. The adjusted one-year graft survival was 84.3 percent for grafts with no mismatches and 77.0 percent for grafts with four mismatches. National rationing of donor organs to achieve minimal mismatching and maximal matching could potentially decrease the average number of HLA mismatches from 3.6 to 1.2, with a corresponding increase in the number of matches, As a consequence, projected five-year graft survival could potentially increase from 58.5 percent to 62.9 percent. This would be associated with a decrease in the proportion of kidneys allocated to black recipients from 22.2 to 15.0 percent. Conclusions, Under ideal circumstances, a policy of maximal matching of cadaveric renal transplants would increase five-year graft survival by a comparatively small 4.4 percentage points, but the actual benefit is likely to be smaller. C1 UNIV MICHIGAN,SCH PUBL HLTH,DEPT HLTH SERV MANAGEMENT & POLICY,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH PUBL HLTH,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. UNIV TEXAS,SCH MED,DIV IMMUNOL & ORGAN TRANSPLANTAT,HOUSTON,TX 77030. UNIV IOWA HOSP & CLIN,DEPT INTERNAL MED,IOWA CITY,IA 52242. URBAN INST,CTR HLTH POLICY,WASHINGTON,DC 20037. NIDDKD,BETHESDA,MD 20892. PRINCETON UNIV,WOODROW WILSON SCH,PRINCETON,NJ 08544. UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT PREVENT MED,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,SCH MED,DIV BIOMETR,BETHESDA,MD 20814. RP HELD, PJ (reprint author), UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,315 W HURON ST,SUITE 240,ANN ARBOR,MI 48103, USA. FU NIDDK NIH HHS [N01-DK-8-2234] NR 24 TC 152 Z9 154 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 22 PY 1994 VL 331 IS 12 BP 765 EP 770 DI 10.1056/NEJM199409223311203 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PG301 UT WOS:A1994PG30100003 PM 8065404 ER PT J AU CRESTEIL, T MARIE, S SONNIER, M KERSUAL, J GONZALEZ, FJ AF CRESTEIL, T MARIE, S SONNIER, M KERSUAL, J GONZALEZ, FJ TI EVIDENCE FOR THE TRANSIENT EXPRESSION OF P-450 DURING THE NEONATAL-PERIOD IN RAT SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE CYTOCHROME P-450; DEVELOPMENT; PURIFICATION ID MICROSOMAL CYTOCHROME-P-450; LIVER CYTOCHROME-P-450; PURIFICATION; ISOZYMES; 3-METHYLCHOLANTHRENE; INDUCTION; SEQUENCE; CDNA AB A cytochrome P-450 N (N for Neonatal) was resolved and partially purified from 15-day-old newborn rat livers. Antibody raised in rabbit against P-450 N detects two bands in liver microsomes, the major one comigrating with the partially purified P-450 N. This protein is not expressed in lung and kidney and exhibits an unusual ontogenic profile in the liver with maximal levels in 2-week-old animals. Expression of P-450 N is not modified in animals given beta-naphthoflavone or pregnenolone 16 alpha-carbonitrile, but is markedly increased by phenobarbital. Its amino-acid composition differs from that of other P-450s and it is not recognized by antibodies directed against CYP1A, CYP2A1, CYP2B, CYP2C11, CYP3A or epoxide hydrolase. It could thus be considered as an unique P-450 expressed transiently before puberty. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP CRESTEIL, T (reprint author), UNIV PARIS 05,INSERM,U75,156 RUE VAUGIRARD,F-75730 PARIS 15,FRANCE. NR 18 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD SEP 21 PY 1994 VL 1208 IS 1 BP 111 EP 117 DI 10.1016/0167-4838(94)90167-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PH592 UT WOS:A1994PH59200016 PM 8086424 ER PT J AU LENFANT, C AF LENFANT, C TI LIFE-STYLE CHANGES, LOW-DOSE DIURETICS SHOULD BE FIRST CHOICE FOR TREATING HYPERTENSION IN THE ELDERLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 31,ROOM 2B19,BETHESDA,MD 20892, USA. NR 3 TC 7 Z9 7 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 SEP 21 PY 1994 VL 272 IS 11 BP 842 EP 842 DI 10.1001/jama.272.11.842 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PG182 UT WOS:A1994PG18200005 PM 8078153 ER PT J AU HOOK, EW SPITTERS, C REICHART, CA NEUMANN, TM QUINN, TC AF HOOK, EW SPITTERS, C REICHART, CA NEUMANN, TM QUINN, TC TI USE OF CELL-CULTURE AND A RAPID DIAGNOSTIC ASSAY FOR CHLAMYDIA-TRACHOMATIS SCREENING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; POLYMERASE CHAIN-REACTION; TESTPACK CHLAMYDIA; INFECTION; WOMEN; CLINICS; SPECIMENS; TESTS; MEN AB Objective.-To compare a rapid, office-based test with standard cell culture for screening of women for Chlamydia trachomatis infections. Design and Settings.-An 8-month prospective crossover trial used alternating screening protocols in two Baltimore (Md) sexually transmitted disease clinics from January 2 through August 14, 1991. Participants.-Consecutive women attending the two clinics who had no indication for administration of antichlamydial antibiotic therapy (eg, history of recent sexual contact with a partner with a sexually transmitted disease, mucopurulent cervicitis, pelvic inflammatory disease, known gonorrhea, or previously diagnosed Chlamydia infections). Interventions.-Chlamydia screening was offered according to one of two protocols. Use of the two screening protocols was alternated between clinics each month. In the ''rapid test clinic,'' eligible women were screened with both a 30-minute enzyme immunoassay test and tissue culture. Patients screened with the rapid test were asked to remain in the clinic until their rapid assay results were available so that, if positive, the patients could be treated. In the ''routine screening clinic,'' eligible women were screened for Chlamydia by cell culture. Women identified as being infected with Chlamydia by screening culture were later confidentially notified of their test results by health department disease intervention specialists and referred for therapy. Main Outcome Measures.-Performance of screening tests for bringing infected patients to therapy; time intervals between initial clinic visits and therapy; and pelvic inflammatory disease occurring between initial visits and therapy. Results.-Chlamydia cultures were positive in 100 (6.6%) of 1526 women screened with the solid-phase immunoassay, 47 of which were detected and treated on the basis of rapid test results. In contrast, 93 (74%) of 126 women with positive screening cultures returned to the clinic and received therapy. The median interval between testing and therapy for women with positive screening cultures was 14 days, and three (3.2%) developed pelvic inflammatory disease in the interval between testing and return for therapy. Conclusions.-Neither cell culture nor a rapid diagnostic test performed well for ensuring therapy of women with Chlamydia infections. The sensitivity of the rapid diagnostic test was low, and nearly one fourth of the women with positive screening cultures did not return for therapy. Evaluation of screening for Chlamydia should consider the utility of strategies for bringing patients to treatment, as well as the more usual measures of test performance, such as sensitivity, specificity, and predictive values. C1 BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT PREVENT MED,BALTIMORE,MD. NIAID,BETHESDA,MD 20892. RP HOOK, EW (reprint author), UNIV ALABAMA,DEPT MED,229 THT,1900 UNIV BLVD,BIRMINGHAM,AL 35294, USA. FU PHS HHS [R30/CCR302723] NR 21 TC 61 Z9 62 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 SEP 21 PY 1994 VL 272 IS 11 BP 867 EP 870 DI 10.1001/jama.272.11.867 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PG182 UT WOS:A1994PG18200025 PM 8078164 ER PT J AU HANCOCK, RD CUKROWSKI, I CUKROWSKA, E HOSKEN, GD ICCHARAM, V BRECHBIEL, MW GANSOW, OA AF HANCOCK, RD CUKROWSKI, I CUKROWSKA, E HOSKEN, GD ICCHARAM, V BRECHBIEL, MW GANSOW, OA TI DESIGN OF LIGANDS CONTAINING THE O-HYDROXYBENZYL GROUP - METAL-COMPLEXING PROPERTIES OF N,N''-BIS(2-HYDROXYBENZYL)DIETHYLENETRIAMINE-N,N',N''-TRIACETIC ACID SO JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS LA English DT Article ID AQUEOUS-SOLUTION; SELECTIVITY; CONSTANTS; IONS; SIZE AB The ligand N,N''-bis(2-hydroxybenzyl)diethylenetriamine-N,N',N''-triacetic acid (H(5)L) has been synthesised and the protonation constants for L determined by potentiometric methods in 0.5 mol dm(-3) NaNO3, and spectrophotometric methods in 0.5 and 0.1 mol dm(-3) NaCl, all at 25 degrees C. The sites of protonation have been inferred from H-1 NMR studies in D2O. The complex formation constants of Ca-II, Zn-II Cd-II, Cu-II, Pb-II and Bi-III have been determined at 25 degrees C by potentiometric methods in 0.5 mol dm(-3) NaNO3, and spectrophotometric methods in 0.5 mol dm(-3) NaCl. The results show that at biological pH the hydroxybenzyl groups tend to remain protonated, and over most of the pH range protonated complexes dominate, with fully deprotonated complexes occurring only at pH values above 9 or 10. The ligand L is, compared to some of its analogues, effectively a weak complexing agent. This is rationalised in terms of the six-membered chelate rings formed in the complex, which include the hydroxybenzyl group. The six-membered chelate rings destabilize complexes of the larger metal ions with which the octadentate ligand should prefer to co-ordinate. C1 UNIV WITWATERSRAND,DEPT CHEM,JOHANNESBURG 2050,SOUTH AFRICA. NCI,CHEM SECT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 19 TC 7 Z9 7 U1 1 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-9246 J9 J CHEM SOC DALTON JI J. Chem. Soc.-Dalton Trans. PD SEP 21 PY 1994 IS 18 BP 2679 EP 2685 DI 10.1039/dt9940002679 PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA PH539 UT WOS:A1994PH53900013 ER PT J AU BRINTON, LA AF BRINTON, LA TI WAYS THAT WOMEN MAY POSSIBLY REDUCE THEIR RISK OF BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PREVENTION; HYPOTHESIS; EXPOSURE RP BRINTON, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 443,6130 EXECUTIVE BLVD,MSC 737,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 23 TC 16 Z9 16 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 SEP 21 PY 1994 VL 86 IS 18 BP 1371 EP 1372 DI 10.1093/jnci/86.18.1371 PG 2 WC Oncology SC Oncology GA PG024 UT WOS:A1994PG02400002 PM 8072025 ER PT J AU GOLDSTEIN, AM FRASER, MC CLARK, WH TUCKER, MA AF GOLDSTEIN, AM FRASER, MC CLARK, WH TUCKER, MA TI AGE AT DIAGNOSIS AND TRANSMISSION OF INVASIVE MELANOMA IN 23 FAMILIES WITH CUTANEOUS MALIGNANT-MELANOMA DYSPLASTIC NEVI SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MYOTONIC-DYSTROPHY; DYSPLASTIC NEVUS; SKIN-CANCER; REPEAT; CHROMOSOME-1P; ANTICIPATION; AUSTRALIA; LOCUS; GENE AB Background: Familial melanoma patients tend to have an earlier age at first melanoma diagnosis, thinner lesions, a different histologic distribution, and a higher frequency of multiple primary melanomas than patients with nonfamilial melanoma. Previous examination of a large melanoma kindred from Texas suggested that although cutaneous malignant melanoma (CMM) was transmitted in an autosomal dominant fashion, there were sex differences in penetrance and disease expression. Purpose: This study further evaluated the age at diagnosis, sex difference in penetrance and disease expression, and segregation of familial CMM. Methods: We evaluated the age at diagnosis and transmission of CMM in 23 U.S. white families with CMM/dysplastic nevi who had been followed 5-17 years. We estimated the median and mean ages at diagnosis of invasive melanoma for all individuals, for men and women separately, and by generation. Using the computer program BMDP1L, we also estimated the cumulative probability of an offspring developing CMM as a function of age according to whether the mother or father had melanoma. In addition, we used a life-table approach to estimate the probability that offspring of CMM parents were affected with CMM (penetrance). Results: The median age at diagnosis in the 23 kindreds (n = 106) was 33 years, substantially less than that of patients with sporadic melanomas in the U.S. white population. For females, the median age at diagnosis was 29 years; for males, it was 36 years. Nine percent of the case patients developed CMM before age 20 compared with 2% in the general population. There was little difference in the transmission pattern of melanoma between males and females in the 23 families, although sons of CMM parents had a higher risk of CMM than daughters of CMM parents. This difference was, however, based on small numbers and was not statistically significant. The penetrance estimates for CMM were high. They rose rapidly from 6% at age 18 to 85% by age 48. The median age at diagnosis of invasive melanoma decreased dramatically in successive generations; the reduction was 11-16 years per generation and was statistically significant (P<.0001). Conclusions and Implications: Although this reduction in median age at diagnosis may result partly from increased surveillance in hereditary melanoma families and the fact that individuals in the younger generations have not yet reached the highest at-risk ages for developing melanoma, the possibility of changes in melanoma risk and risk factors, genetic and/or environmental, across generations should be considered. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. UNIV PENN,SCH MED,PIGMENTED LES STUDY GRP,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT DERMATOL,PHILADELPHIA,PA 19104. RP GOLDSTEIN, AM (reprint author), NCI,DIV CANC ETIOL,GENET EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 439,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 33 TC 30 Z9 30 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 SEP 21 PY 1994 VL 86 IS 18 BP 1385 EP 1390 DI 10.1093/jnci/86.18.1385 PG 6 WC Oncology SC Oncology GA PG024 UT WOS:A1994PG02400008 PM 8072031 ER PT J AU JAIN, M MILLER, AB TO, T AF JAIN, M MILLER, AB TO, T TI PREMORBID DIET AND THE PROGNOSIS OF WOMEN WITH BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURVIVAL; RISK; FAT; HABITS; COHORT; QUESTIONNAIRE; EPIDEMIOLOGY; RECEPTORS; WEIGHT; MODELS AB Background: Consumption of a high-fat diet has been associated with poor survival in breast cancer patients. However, studies examining this association are limited and have not used adjustment of energy in their estimates. Purpose: The effect of usual diet before diagnosis of breast cancer on the risk of dying of breast cancer was examined in a cohort of women with breast cancer from the National Breast Screening Study (NBSS) in Canada. Methods: From a cohort of 89 835 women in the NBSS, a total of 1270 histologically confirmed cases of invasive carcinoma of the breast were identified by active follow-up, supplemented by passive follow-up involving record linkage to provincial cancer registries. Of these, 678 case patients who had completed a diet history and were diagnosed from January 1982 up to June 1992 formed the cohort for this investigation. Diet was ascertained from a self-administered diet-history questionnaire. Mortality data were obtained by linkage to the Canadian Mortality Data Base of Statistics Canada, provincial cancer registries, and annual follow-up of cases through physicians. Risk of dying and survival probabilities were estimated by the Cox proportional hazards method and the actuarial life-table method. Results: There were 83 deaths in this study cohort of 678 women; 76 deaths were due to breast cancer, and the remaining seven resulted from other causes. The 5-year survival rate was 90%. For every 5% increase in energy from saturated fat, the risk of dying of breast cancer increased by 50% (hazard ratio = 1.50; 95% confidence interval [CI]: 1.08-2.08). No significant increase in risk was seen with total fat intake (hazard ratio = 1.21; 95% CI = 0.91-1.61) or oleic acid intake (hazard ratio = 1.25; 95% CI = 0.90-1.74). There was a lower risk of dying of breast cancer in the highest quartiles of beta carotene intake (hazard ratio = 0.48; 95% CI = 0.23-0.99) and vitamin C intake (hazard ratio = 0.43; 95% CI: 0.21-0.86); both vitamins showed a significant dose-response relationship (P for trend, less than or equal to.05). These effects varied with menopausal status at diagnosis and tumor characteristics. Conclusions: These results suggest an increased risk of dying of breast cancer with higher intakes of saturated fat before diagnosis and slightly reduced risk with higher intakes of beta carotene and vitamin C. implications: More attention should be paid to premorbid dietary habits in relation to breast cancer prognosis. Further studies, however, need to be done with ascertainment of dietary changes prior to and subsequent to diagnosis. C1 SUNNYBROOK HLTH SCI CTR,INST CLIN EVALUAT SCI,N YORK,ON,CANADA. RP JAIN, M (reprint author), UNIV TORONTO,DEPT PREVENT MED & BIOSTAT,NCI,EPIDEMIOL UNIT,MCMURRICH BLDG,TORONTO M5S 1A8,ON,CANADA. NR 33 TC 93 Z9 93 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 21 PY 1994 VL 86 IS 18 BP 1390 EP 1397 DI 10.1093/jnci/86.18.1390 PG 8 WC Oncology SC Oncology GA PG024 UT WOS:A1994PG02400009 PM 8072032 ER PT J AU RISCH, HA JAIN, M MARRETT, LD HOWE, GR AF RISCH, HA JAIN, M MARRETT, LD HOWE, GR TI DIETARY-FAT INTAKE AND RISK OF EPITHELIAL OVARIAN-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STATES CASE-CONTROL; COLLABORATIVE ANALYSIS; WOMEN; MORTALITY; PATHOGENESIS; VEGETARIAN; FOOD AB Background: Evidence exists that dietary fat may be a contributory factor in the development of hormone-related cancers such as ovarian cancer. Previous studies have demonstrated significantly higher circulating-estrogen levels among nonvegetarian women than among vegetarian women; the increase correlated directly with consumption of saturated fat, However, the contribution that dietary fat plays in the development of hormone-related cancers remains unresolved. Purpose: Our purpose was to evaluate whether saturated fat intake increases the risk of ovarian cancer development. Methods: Population-based sampling was used to acquire cases and controls over a 3-year period from the study area, which included the highly populated region surrounding the western end of Lake Ontario, Canada. From the Ontario Cancer Registry, all histologically confirmed, primary malignant or borderline malignant epithelial ovarian tumors first diagnosed from November 1989 through October 1992 among study-area residents aged 35-79 years were determined. In total, 631 eligible case subjects were identified, of whom 450 (71.3%) were interviewed concerning reproduction and diet; 564 randomly selected population control subjects were similarly interviewed. From the quantitative diet-history information, average daily intakes of macronutrients and micronutrients were calculated. Unconditional continuous logistic regression methods were used for analysis, with adjustment for age at interview, number of full-term pregnancies, years of oral contraceptive use, and total daily caloric intake. Results: Saturated fat consumption was associated with increasing risk of ovarian cancer (odds ratio [OR] = 1.20 for each 10 g/day of intake; 95% confidence interval [CI] = 1.03-1.40; one-sided P =.0082). No relationship was seen with intake of unsaturated fats. Egg consumption also appeared related to increased risk (OR = 1.42 for each 100 mg of egg cholesterol per day; 95% CI = 1.18-1.72; two-sided P = .0002), though this association may have resulted from disease-related changes in the dietary practices of case subjects prior to diagnosis. Consumption of vegetable fiber (but not fruit or cereal fiber) was associated with decreased risk (OR = 0.63 for each 10 g/day; 95% CI = 0.49-0.80; two-sided P =.0001). All three nutrients (saturated fat, egg cholesterol, and vegetable fiber) remained statistically significant when included in the same regression model. Conclusion: Diet may contribute to risk of ovarian cancer development. Implication: If confirmed in further studies, this association may allow women to appreciably lower their risk of ovarian cancer through dietary modifications: reducing the intake of saturated fats and eating more vegetables. C1 UNIV TORONTO,DEPT PREVENT MED & BIOSTAT,NCI,EPIDEMIOL UNIT,TORONTO,ON,CANADA. ONTARIO CANC TREATMENT & RES FDN,TORONTO,ON,CANADA. RP RISCH, HA (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,60 COLL ST,POB 3333,NEW HAVEN,CT 06510, USA. NR 49 TC 103 Z9 103 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 21 PY 1994 VL 86 IS 18 BP 1409 EP 1415 DI 10.1093/jnci/86.18.1409 PG 7 WC Oncology SC Oncology GA PG024 UT WOS:A1994PG02400012 PM 8072035 ER PT J AU MCLAUGHLIN, JK FRAUMENI, JF OLSEN, J MELLEMKJAER, L AF MCLAUGHLIN, JK FRAUMENI, JF OLSEN, J MELLEMKJAER, L TI BREAST IMPLANTS, CANCER, AND SYSTEMIC-SCLEROSIS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID AUGMENTATION; RISK C1 DANISH CANC REGISTRY,COPENHAGEN,DENMARK. RP MCLAUGHLIN, JK (reprint author), NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD, USA. NR 7 TC 44 Z9 44 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 SEP 21 PY 1994 VL 86 IS 18 BP 1424 EP 1424 DI 10.1093/jnci/86.18.1424 PG 1 WC Oncology SC Oncology GA PG024 UT WOS:A1994PG02400015 PM 8072038 ER PT J AU CAMPAIN, JA GOTTESMAN, MM PASTAN, I AF CAMPAIN, JA GOTTESMAN, MM PASTAN, I TI A NOVEL MUTANT TOPOISOMERASE II-ALPHA PRESENT IN VP-16-RESISTANT HUMAN-MELANOMA CELL-LINES HAS A DELETION OF ALANINE-429 SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; AMSACRINE-MEDIATED FORMATION; DNA TOPOISOMERASE; ESCHERICHIA-COLI; POINT MUTATION; DRUG-RESISTANCE; LEUKEMIA-CELLS; CYTO-TOXICITY; PHORBOL ESTER; GYRB GENE AB The human melanoma cell line FEM-X was selected in multiple steps with VP-16 (etoposide) and an inhibitor of P-glycoprotein (Campain ef al., 1993). The resulting clones, FVP1b and FVP3, are highly resistant to the nonintercalative epipodophyllotoxins and exhibit moderate levels of resistance to doxorubicin. The topoisomerase II activity present in crude nuclear extracts from mutant and wild-type cells is similar in amount and equally sensitive to VP-16. However, in live cells, the topoisomerase II from FVP1b and FVP3 is much less susceptible to drug-induced cleavable complex formation than is that from FEM-X. Using reverse transcription followed by the polymerase chain reaction (RT-PCR), we have cloned and sequenced the entire cDNA for topoisomerase II alpha from FEM-X and FVP3. The only sequence change unique to the cDNA from drug-resistant cells is a 3 bp deletion of nucleotide 1320-1322, resulting in a deletion of Ala429. Three FEM-X sublines of increasing resistance were tested, and the prevalence of the mutant RNA over wild-type increases in these cells in parallel with their resistance to VP-16. In FVP3, the most highly resistant line, expression of the wild-type allele is barely detectable. Analysis of genomic DNA shows that FEM-X is homozygous for the wild-type topoisomerase II alpha sequence and that each of the drug-resistant clones possesses both wild-type and mutant alleles. Although not definitive, these genetic results suggest that the deletion of Ala429 from topoisomerase II alpha makes the enzyme less susceptible to drug-induced cleavable complex formation and confers a growth advantage upon cells in the presence of VP-16. Since topoisomerase II alpha activity in extracts from these drug-resistant FEM-X lines is normally sensitive to drugs, the deletion of an Ala at residue 429 may alter intracellular localization of the enzyme or change its interaction with other factors, which could then decrease the DNA-topoisomerase II alpha complexes trapped in the presence of VP-16. However, proof that the mutant topoisomerase II alpha is responsible for drug resistance requires its successful expression in drug-sensitive cells. C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,DCBDC,CELL BIOL LAB,BETHESDA,MD 20892. NR 52 TC 31 Z9 31 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 20 PY 1994 VL 33 IS 37 BP 11327 EP 11332 DI 10.1021/bi00203a030 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PH174 UT WOS:A1994PH17400030 PM 7727383 ER PT J AU IDRISS, H KUMAR, A CASASFINET, JR GUO, H DAMUNI, Z WILSON, SH AF IDRISS, H KUMAR, A CASASFINET, JR GUO, H DAMUNI, Z WILSON, SH TI REGULATION OF IN-VITRO NUCLEIC-ACID STRAND ANNEALING ACTIVITY OF HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN PROTEIN AL BY REVERSIBLE PHOSPHORYLATION SO BIOCHEMISTRY LA English DT Article ID PRE-MESSENGER-RNA; BOVINE KIDNEY CORTEX; DNA-BINDING PROTEINS; PROTAMINE-KINASE; PREMESSENGER-RNA; HNRNP PROTEINS; COMPLEX PROTEIN-A1; TERMINAL DOMAIN; CORE PROTEINS; PHOSPHATASE-2A AB Phosphorylation in vivo of several proteins in the mammalian heterogeneous nuclear ribonucleoprotein complex (hnRNP), including A1, has been observed and proposed as a regulatory step in pre-mRNA splicing [Mayrand, S. H., Dwen, P., and Pederson, T. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7764-7768]. We examined the ability of recombinant hnRNP protein Al to act as a substrate for a number of purified Ser/Thr protein kinases in vitro. A survey of seven protein kinases showed that A1 was heavily phosphorylated by protein kinase C (PKC) and also was phosphorylated by casein kinase II, protamine kinase, and protein kinase A. In contrast, autophosphorylation-activated protein kinase and two forms of myelin basic protein kinase failed to phosphorylate A1, Proteolysis with trypsin and V8 protease revealed that PKC phosphorylates Al at three main sites, two in the N-terminal domain (spanning residues 2-196) and one in the C-terminal domain (spanning residues 197-320). Amino acid sequencing revealed that these sites were Ser(95), Ser(192), and Ser(199); phosphorylation at Ser(192) was more abundant than at Ser(95) and Ser(199). Phosphorylation by PKC inhibited the strand annealing activity of A1. Protein phosphatase 2A, but not protein phosphatase 1, dephosphorylated A1 and reversed the inhibitory effect of PKC phosphorylation on the strand annealing activity. A conformational change in the C-terminal domain of A1 was observed upon PKC phosphorylation, and this was associated with a decrease in A1's affinity for single-stranded polynucleotides. The results are consistent with a role of phosphorylation of A1 in regulating its strand annealing activity in vivo. C1 UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX 77555. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,STRUCT BIOCHEM LAB,FREDERICK,MD 21702. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. NR 53 TC 39 Z9 39 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 20 PY 1994 VL 33 IS 37 BP 11382 EP 11390 DI 10.1021/bi00203a037 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PH174 UT WOS:A1994PH17400037 PM 7727389 ER PT J AU MAKINO, S GOLD, PW SCHULKIN, J AF MAKINO, S GOLD, PW SCHULKIN, J TI EFFECTS OF CORTICOSTERONE ON CRH MESSENGER-RNA AND CONTENT IN THE BED NUCLEUS OF THE STRIA TERMINALIS - COMPARISON WITH THE EFFECTS IN THE CENTRAL NUCLEUS OF THE AMYGDALA AND THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS SO BRAIN RESEARCH LA English DT Article DE CORTICOSTERONE; CORTICOTROPIN-RELEASING HORMONE; BED NUCLEUS OF THE STRIA TERMINALIS; MESSENGER-RNA; AMYGDALA; PARAVENTRICULAR NUCLEUS ID CORTICOTROPIN-RELEASING-FACTOR; FACTOR-LIKE IMMUNOREACTIVITY; MESSENGER RIBONUCLEIC-ACID; RAT-BRAIN REGIONS; BIOCHEMICAL MANIFESTATIONS; CELLULAR ARCHITECTURE; PARABRACHIAL NUCLEUS; ACOUSTIC STARTLE; PREOPTIC AREA; STRESS AB We previously reported that corticosterone (CORT) increased corticotropin-releasing hormone (CRH) mRNA in the central nucleus of the amygdala (CEA), while reducing it in the paraventricular nucleus (PVN) of the hypothalamus by using in situ hybridization histochemistry. The bed nucleus of the stria terminalis (BNST) is closely related to the amygdala, and it is also a source of extrahypothalamic CRH; therefore, we examined CRH mRNA changes in the BNST following systemic treatment with CORT in adrenally-intact rats. Effects of adrenalectomy on CRH mRNA in the BNST, PVN and CEA were also examined. In addition, CRH content in these nuclei and in the median eminence (ME) were determined by micropunch dissection technique combined with CRH radioimmunoassay in CORT pellet implanted rats. Subcutaneous injections of high CORT (5 mg/day, over 14 days) increased CRH mRNA in the dorsal part of the lateral BNST (BSTLD) at 2, 4 and 8 days, although the low dose of CORT (1 mg/kg/day) had no significant effects. By contrast, in the ventral part of the BNST (BSTV) neither the high nor low dose of CORT altered CRH mRNA levels. In a second experiment, a slowly-releasing CORT pellet (200 mg, 60-day release) ,produced an elevation of CRH mRNA at both 1 and 2 weeks or at 1 week in the BSTLD or in the BSTV, respectively. These results show that glucocorticoids can facilitate CRH mRNA expression in the BSTLD in the same manner as seen in the CEA, and that CRH mRNA in the BSTLD can respond to CORT more than in the BSTV. In a third experiment, bilateral adrenalectomy, however, did not affect CRH mRNA in the BNST although there was a modest decrease in the CEA and a robust increase in the PVN. Finally, in CORT pellet (200 mg, for 2 weeks) implanted rats, CRH content in the ME significantly decreased and modestly increased in the CEA compared with control rats, whereas it did not change in the PVN and BNST. Taken together, these results suggest that (1) CRH in the BNST and the CEA may share some common functions in neuroendocrine and behavioral changes, but that (2) mechanisms of CRH synthesis or its releasing sites may be different in the BNST and CEA. RP NIMH, CLIN NEUROENDOCRINOL BRANCH, BLDG 10, ROOM 35-231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 57 TC 174 Z9 176 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD SEP 19 PY 1994 VL 657 IS 1-2 BP 141 EP 149 DI 10.1016/0006-8993(94)90961-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA PG393 UT WOS:A1994PG39300016 PM 7820612 ER PT J AU INOUE, K CREVELING, CR KARASAWA, N ISOMURA, G NAGATSU, I AF INOUE, K CREVELING, CR KARASAWA, N ISOMURA, G NAGATSU, I TI MEASUREMENT OF DOPA AND IMMUNOLOCALIZATION OF L-DOPA-POSITIVE NERVE-FIBERS IN RAT DENTAL-PULP SO BRAIN RESEARCH LA English DT Note DE 3,4-DIHYDROXYPHENYLALAMINE; NERVE FIBER; DENTAL PULP; RAT; MEASUREMENT; IMMUNOLOCALIZATION ID ENDOGENOUS L-DOPA; IMMUNOREACTIVITY; NEURONS AB DOPA, norepinephrine, and traces of dopamine, epinephrine were present in rat dental pulp. L-DOPA was localized in nerve fibers in dental pulp. The results suggest that L-DOPA-positive nerve fibers are present in dental pulp as well as classical adrenergic fibers. C1 NIH,BIOORGAN CHEM LAB,BETHESDA,MD. FUJITA HLTH UNIV,SCH MED,DEPT ANAT,AICHI,JAPAN. RP INOUE, K (reprint author), MATSUMOTO DENT COLL,INST DENT SCI,1780 GOBARA HIROOKA,SHIOJIRI,NAGANO 39907,JAPAN. NR 22 TC 4 Z9 4 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 SEP 19 PY 1994 VL 657 IS 1-2 BP 307 EP 309 DI 10.1016/0006-8993(94)90981-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA PG393 UT WOS:A1994PG39300036 PM 7820632 ER PT J AU GOEDERT, JJ COHEN, AR KESSLER, CM EICHINGER, S SEREMETIS, SV RABKIN, CS YELLIN, FJ ROSENBERG, PS ALEDORT, LM AF GOEDERT, JJ COHEN, AR KESSLER, CM EICHINGER, S SEREMETIS, SV RABKIN, CS YELLIN, FJ ROSENBERG, PS ALEDORT, LM TI RISKS OF IMMUNODEFICIENCY, AIDS, AND DEATH RELATED TO PURITY OF FACTOR-VIII CONCENTRATE SO LANCET LA English DT Note ID INFECTED HEMOPHILIACS AB In HIV-infected subjects with haemophilia, CD4 counts seem to fall more slowly in those on high-purity factor VIII (FVIII) than on intermediate-purity product. We evaluated whether risks for AIDS or death were associated with either product among 411 HIV-infected individuals. The relative hazard of AIDS was slightly elevated for both current (1.34 per month) and cumulative (1.01 per month) use of high-purity products (neither significant). The corresponding hazards for death were 1.49 and 1.03 (neither significant). Thus we found no evidence that high-purity FVIII concentrates retard the development of AIDS. C1 NCI,VIRAL EPIDEMIOL BRANCH,AIDS & CANC SECT,ROCKVILLE,MD. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. GEORGE WASHINGTON UNIV HOSP,WASHINGTON,DC. UNIV VIENNA,VIENNA,AUSTRIA. MT SINAI MED CTR,NEW YORK,NY 10029. COMP SCI CORP,PROFESS SERV GRP,ROCKVILLE,MD. NCI,EPIDEMIOL METHODS SECT,ROCKVILLE,MD. NR 9 TC 45 Z9 45 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 17 PY 1994 VL 344 IS 8925 BP 791 EP 792 DI 10.1016/S0140-6736(94)92345-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PG178 UT WOS:A1994PG17800014 PM 7916077 ER PT J AU DONOVAN, JA WANGE, RL LANGDON, WY SAMELSON, LE AF DONOVAN, JA WANGE, RL LANGDON, WY SAMELSON, LE TI THE PROTEIN PRODUCT OF THE C-CBL PROTOONCOGENE IS THE 120-KDA TYROSINE-PHOSPHORYLATED PROTEIN IN JURKAT CELLS ACTIVATED VIA THE T-CELL ANTIGEN RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ZETA-CHAIN; SIGNAL TRANSDUCTION; LYMPHOCYTES-T; V-CBL; KINASE; SH2; ASSOCIATION; ONCOGENE; BINDING; ZAP-70 AB Tyrosine phosphorylation of multiple cellular proteins is a critical event in T cell receptor (TCR)-mediated activation. This pathway has also been implicated in cellular transformation in multiple systems. The viral oncogene v-cbl is the transforming gene of a murine retrovirus that induces pre-B cell lymphomas and myelogenous leukemias. The product of its cellular homolog, p120(cbl), is a 120-kDa cytoplasmic protein that is nontransforming when overexpressed. Here we show that the 120-kDa protein tyrosine phosphorylated in Jurkat T cells upon TCR engagement is p120(cbl). Following stimulation through the TCR, this tyrosine phosphorylation is rapid and reversible. Tyrosine-phosphorylated p120(cbl) binds to glutathione S-transferase fusion proteins generated from SH2 domains of the Fyn, Lck, and Blk protein tyrosine kinases, GTPase-activating protein and phospholipase Cy. The p120(cbl) from unactivated and activated cells also binds to full-length glutathione S-transferase-Grb2 and the Grb2 N-terminal SH3 domain, but not to the Grb2 C-terminal SH3 domain. Additionally, p120(cbl) binds to SH3 domains of Fyn and Lck, but not Blk. These data expand our knowledge of protein tyro sine kinase signaling pathways in T cells by identifying a prominent tyrosine kinase substrate. This protein, the product of the cellular homolog of a transforming oncogene, can interact with several known signaling molecules. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. UNIV WESTERN AUSTRALIA,DEPT BIOCHEM,NEDLANDS,WA 6009,AUSTRALIA. NR 35 TC 300 Z9 303 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 16 PY 1994 VL 269 IS 37 BP 22921 EP 22924 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400003 PM 8083187 ER PT J AU LIOTTA, AS KOLE, HK FALES, HM ROTH, J BERNIER, M AF LIOTTA, AS KOLE, HK FALES, HM ROTH, J BERNIER, M TI A SYNTHETIC TRIS-SULFOTYROSYL DODECAPEPTIDE ANALOG OF THE INSULIN-RECEPTOR 1146-KINASE DOMAIN INHIBITS TYROSINE DEPHOSPHORYLATION OF THE INSULIN-RECEPTOR IN-SITU SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSYL-PROTEIN PHOSPHATASES; GROWTH-FACTOR RECEPTORS; AUTOPHOSPHORYLATION SITES; KINASE-ACTIVITY; HUMAN-PLACENTA; PARTICULATE; PHOSPHORYLATION; PEPTIDE; BETA AB A synthetic tris-sulfotyrosyl dodecapeptide (TRDIY-(S)ETDY(S)Y(S)RK-amide), whose primary sequence is identical to the 1142-1153 sequence of the insulin proreceptor, inhibited insulin receptor dephosphorylation in solubilized membranes, and digitonin-permeabilized cells derived from Chinese hamster ovary (CHO) cells expressing high levels of human insulin receptors (CHO/HIRc). It also inhibited the dephosphorylation of a synthetic tyrosine phosphorylated substrate by recombinant PTP-1B, a protein tyrosine phosphatase (PTPase), indicating that it acted via interaction with PTPase(s). A N-stearyl derivative of the peptide caused an similar to 4.5-fold increase in insulin-stimulated receptor autophosphorylation in intact CHO/HIRe cells. The peptide displayed specificity toward tyrosine-class phosphatases only, as it had no effect on the activities of the serine/threonine phosphatases PP-1 and PP-2A, or alkaline phosphatase. The tyrosine sulfate ester bonds of the peptide were stable when incubated with PTP-1B (1 h, 30 degrees C). These data suggest that the sulfotyrosyl peptide functions as a nonhydrolyzable phosphotyrosyl peptide analogue capable of direct interaction with PTPase catalytic domain. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,DIABET UNIT,BALTIMORE,MD 21224. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. OI Bernier, Michel/0000-0002-5948-368X NR 34 TC 52 Z9 55 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 SEP 16 PY 1994 VL 269 IS 37 BP 22996 EP 23001 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400017 PM 8083198 ER PT J AU GERMANO, P GOMEZ, J KAZANIETZ, MG BLUMBERG, PM RIVERA, J AF GERMANO, P GOMEZ, J KAZANIETZ, MG BLUMBERG, PM RIVERA, J TI PHOSPHORYLATION OF THE GAMMA-CHAIN OF THE HIGH-AFFINITY RECEPTOR FOR IMMUNOGLOBULIN-E BY RECEPTOR-ASSOCIATED PROTEIN-KINASE C-DELTA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; TYROSINE KINASE; T-CELL; SIGNAL-TRANSDUCTION; RBL-2H3 CELLS; ZETA-CHAIN; MAST-CELLS; HISTAMINE-RELEASE; PHORBOL ESTER AB The gamma chain of the high affinity receptor for immunoglobulin E is a member of the T-cell antigen receptor zeta chain family and a functional subunit common to both T-cell and Fc receptors. Here we report that the gamma chain is phosphorylated on threonine in response to protein kinase C activation. Furthermore, the threonine phosphorylation of the gamma chain correlates with the endocytosis of this receptor. We identified a receptor-associated kinase as the calcium-independent protein kinase C-delta and found that it associates with the carboxyl-terminal cytoplasmic domain of the beta chain. In addition, protein kinase C-delta was the only isozyme capable of phosphorylating the gamma chain in vitro. These findings provide evidence for the functional role of protein kinase C-delta in early signal transduction events in the mast cell and suggest a more general mechanism of activation for receptors that share subunits of the zeta chain family. C1 NIAMSD,CHEM IMMUNOL SECT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 38 TC 54 Z9 54 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 SEP 16 PY 1994 VL 269 IS 37 BP 23102 EP 23107 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400033 PM 8083212 ER PT J AU JENNINGS, GT SECHI, S STEVENSON, PM TUCKEY, RC PARMELEE, D MCALISTERHENN, L AF JENNINGS, GT SECHI, S STEVENSON, PM TUCKEY, RC PARMELEE, D MCALISTERHENN, L TI CYTOSOLIC NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE - ISOLATION OF RAT CDNA AND STUDY OF TISSUE-SPECIFIC AND DEVELOPMENTAL EXPRESSION OF MESSENGER-RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE MAMMARY-GLAND; NADP+; MITOCHONDRIAL; PURIFICATION; SEQUENCE; PROTEINS; DNA; OVARY AB Immunoscreening and DNA hybridization were used to isolate a 1.72-kilobase pair cDNA encoding cytosolic NADP(+)-dependent isocitrate dehydrogenase from a rat liver, lambda gt11 cDNA library. The identity of the cDNA was confirmed by comparison of the deduced amino acid sequence with sequences of peptides obtained from purified ovarian cytosolic isocitrate dehydrogenase. The 1.72-kilobase pair cDNA sequence translated into a protein of 414 amino acid residues with a molecular mass of 46,681 Da. The amino acid sequence contains a tripeptide (AKL) at the COOH terminus which represents a possible peroxisomal targeting sequence. The deduced amino acid sequence of the rat liver cytosolic isocitrate dehydrogenase showed 70 and 59% identity with sequences reported for NADP(+)-dependent isocitrate dehydrogenases from porcine mitochondria and yeast cytosol respectively. Northern blot analysis demonstrated a 13-fold increase in expression of cytosolic NADP(+)-dependent isocitrate dehydrogenase mRNA during the gonadotropin-induced development of the immature rat ovary. In comparative studies, the cytosolic and mitochondrial isocitrate dehydrogenase mRNAs were found to differ in size (2.2 and 1.8 kilobases, respectively) and to be differentially expressed in various tissues of the rat. Distinct digestion patterns were also obtained in Southern blot analysis of rat genomic DNA. C1 UNIV WESTERN AUSTRALIA,DEPT BIOCHEM,NEDLANDS,WA 6009,AUSTRALIA. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20894. RP JENNINGS, GT (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. RI Tuckey, Robert/H-5983-2014 FU NIGMS NIH HHS [GM51265] NR 32 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 SEP 16 PY 1994 VL 269 IS 37 BP 23128 EP 23134 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400037 PM 8083215 ER PT J AU YOKOTA, H FERNANDEZSALGUERO, P FURUYA, H LIN, KM MCBRIDE, OW PODSCHUN, B SCHNACKERZ, KD GONZALEZ, FJ AF YOKOTA, H FERNANDEZSALGUERO, P FURUYA, H LIN, KM MCBRIDE, OW PODSCHUN, B SCHNACKERZ, KD GONZALEZ, FJ TI CDNA CLONING AND CHROMOSOME MAPPING OF HUMAN DIHYDROPYRIMIDINE DEHYDROGENASE, AN ENZYME ASSOCIATED WITH 5-FLUOROURACIL TOXICITY AND CONGENITAL THYMINE URACILURIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEVERE FLUOROURACIL TOXICITY; DIHYDROTHYMINE DEHYDROGENASE; FAMILIAL PYRIMIDINEMIA; CANCER-PATIENTS; HUMAN-LIVER; RAT-LIVER; PIG-LIVER; DEFICIENCY; PURIFICATION; PROTEINS AB The pig and human dihydropyrimidine dehydrogenase (DPD) cDNAs were cloned and sequenced. The pig enzyme, expressed in Escherichia coli, catalyzed the reduction of uracil, thymine, and 5-fluorouracil with kinetics approximating those published for the enzyme purified from mammalian liver. DPD could be expressed in significant quantities only when uracil was added to the bacterial growth medium. The pig and human enzymes contained 1025 amino acids and calculated M(r) = 111,416 and 111,398, respectively. Conserved domains corresponding to a possible NADPH binding site and FAD binding site were found in the NH2-terminal half of the proteins and two motifs of putative [4Fe-4S] binding sites were found near to the carboxyl terminus of the enzyme. The latter corresponds to the labile COOH-terminal fragment previously shown to contain the iron sulfur centers. A sequence encompassing a peptide corresponding to the uracil binding site was found between the NADPH/FAD-containing NH2-terminal portion of the protein and the iron-sulfur binding sites near to the COOH terminus. Thus, the DPD appears to be derived from at least three distinct domains. The DPYD gene was localized to the centromeric region of human chromosome 1 between 1p22 and q21. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. THEODOR BOVERI INST BIOWISSENSCH,D-97074 WURZBURG,GERMANY. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 44 TC 107 Z9 113 U1 1 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 SEP 16 PY 1994 VL 269 IS 37 BP 23192 EP 23196 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400046 PM 8083224 ER PT J AU BATTEY, FD GAFVELS, ME FITZGERALD, DJ ARGRAVES, WS CHAPPELL, DA STRAUSS, JF STRICKLAND, DK AF BATTEY, FD GAFVELS, ME FITZGERALD, DJ ARGRAVES, WS CHAPPELL, DA STRAUSS, JF STRICKLAND, DK TI THE 39-KDA RECEPTOR-ASSOCIATED PROTEIN REGULATES LIGAND-BINDING BY THE VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEPHRITIS ANTIGENIC COMPLEX; ACTIVATOR INHIBITOR TYPE-1; ALPHA-2-MACROGLOBULIN RECEPTOR; LDL-RECEPTOR; PLASMINOGEN-ACTIVATOR; HEYMANN NEPHRITIS; CELL-SURFACE; IN-VITRO; GLYCOPROTEIN; VIVO AB A 39-kDa receptor associated protein (RAP) binds and inhibits ligand binding by two members of the low density lipoprotein (LDL) receptor family, gp330 and low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor. To determine if additional members of the LDL receptor family may interact with RAP, Chinese hamster ovary cells were transfected with plasmids directing expression of the very low density lipoprotein (VLDL) receptor cDNA or the LDL receptor cDNA Detergent-soluble extracts from these and normal Chinese hamster ovary cells were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, after which the proteins were transferred to nitrocellulose membranes and incubated with RAP. When detergent extracts from normal cells were incubated with RAP, several polypeptides, including a 130-kDa protein, were observed to bind RAP. In cells transfected with the VLDL receptor cDNA, a substantial increase in RAP binding to the 130-kDa polypeptide was noted. This protein was identified as the VLDL receptor by immunoblotting. The VLDL receptor present in detergent extracts from transfected cells bound to RAP-Sepharose, and a K-D of 0.7 nM for the interaction between RAP and the purified VLDL receptor was determined using enzyme-linked immunosorbant assay. The purified VLDL receptor bound I-125-labeled VLDL, but not I-125-labeled LDL, and the binding of I-125-labeled VLDL was completely inhibited by RAP. Further, RAP inhibited the uptake and degradation of I-125-VLDL by cells overexpressing the VLDL receptor. Thus the VLDL receptor represents the third member of the LDL receptor family whose ligand binding properties are antagonized by RAP. This suggests a common functional role for RAP in modulating ligand binding by members of the LDL receptor family. C1 AMER RED CROSS,HOLLAND LAB,DEPT BIOCHEM,ROCKVILLE,MD 20855. UNIV IOWA,COLL MED,DEPT MED,IOWA CITY,IA 52242. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT OBSTET & GYNAECOL,PHILADELPHIA,PA 19104. FU NHLBI NIH HHS [HL49264, HL50787]; NIGMS NIH HHS [GM42581] NR 39 TC 166 Z9 166 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 SEP 16 PY 1994 VL 269 IS 37 BP 23268 EP 23273 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400056 PM 8083232 ER PT J AU CUSHMAN, M GOLEBIEWSKI, WM MCMAHON, JB BUCKHEIT, RW CLANTON, DJ WEISLOW, O HAUGWITZ, RD BADER, JP GRAHAM, L RICE, WG AF CUSHMAN, M GOLEBIEWSKI, WM MCMAHON, JB BUCKHEIT, RW CLANTON, DJ WEISLOW, O HAUGWITZ, RD BADER, JP GRAHAM, L RICE, WG TI DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF COSALANE, A NOVEL ANTI-HIV AGENT WHICH INHIBITS MULTIPLE FEATURES OF VIRUS REPRODUCTION SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; AIDS-RELATED COMPLEX; LYMPHADENOPATHY-ASSOCIATED VIRUS; AURINTRICARBOXYLIC ACID ATA; PLACEBO-CONTROLLED TRIAL; MOLECULAR-WEIGHT; DEXTRAN SULFATE; REPLICATION INVITRO; AZIDOTHYMIDINE AZT AB Cosalane (3), a novel anti-HIV agent having a disalicylmethane unit linked to C-3 of cholestane by a three-carbon Linker, was synthesized from commercially available starting materials by a convergent route. Cosalane proved to be a potent inhibitor of HIV with a broad range of activity against a variety of laboratory, drug-resistant, and clinical HIV-1 isolates, HIV-2, and Rauscher murine leukemia virus. The cytotoxicity of cosalane is relatively low as reflected by an in vitro therapeutic index of > 100. Although cosalane inhibits HIV-1 reverse transcriptase and protease, time of addition experiments indicate that it prevents the cytopathic effect of HIV by acting earlier than reverse transcription in the viral replication cycle. The available evidence indicates that the primary mechanism of action of cosalane involves inhibition of gp120-CD4 binding as well as inhibition of a postattachment event prior to reverse transcription. C1 PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,PROGRAM RESOURCES,ANTIAIDS VIRUS DRUG SCREENING L,FREDERICK,MD 21702. SRA TECHNOL INC,ROCKVILLE,MD 20850. NCI,DRUG SYNTH & CHEM BRANCH,ROCKVILLE,MD 20852. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,ROCKVILLE,MD 20852. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CM-17513, N01-CM-37818, N01-CO-74102] NR 51 TC 57 Z9 57 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 16 PY 1994 VL 37 IS 19 BP 3040 EP 3050 DI 10.1021/jm00045a008 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PH073 UT WOS:A1994PH07300008 PM 7932526 ER PT J AU BERTHA, CM MATTSON, MV FLIPPENANDERSON, JL ROTHMAN, RB XU, H CHA, XY BECKETTS, K RICE, KC AF BERTHA, CM MATTSON, MV FLIPPENANDERSON, JL ROTHMAN, RB XU, H CHA, XY BECKETTS, K RICE, KC TI A MARKED CHANGE OF RECEPTOR AFFINITY OF THE 2-METHYL-5-(3-HYDROXYPHENYL)MORPHANS UPON ATTACHMENT OF AN (E)-8-BENZYLIDENE MOIETY - SYNTHESIS AND EVALUATION OF A NEW CLASS OF SIGMA-RECEPTOR LIGANDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG BRAIN; OPIOID BINDING-SITES; H-3 (+)-PENTAZOCINE; OPIATE RECEPTOR; PHENCYCLIDINE; IDENTIFICATION; HALOPERIDOL; DRUGS; MEMBRANES; ANALOGS AB The (E)-8-benzylidene and (E)-8-(3,4-dichlorobenzylidene), 7-ketone derivatives, 5 and 6, of the synthetic opiate 2-methyl-5-(3-hydraxyphenyl)morphan [5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1], were synthesized from the 7-ketone derivatives 2 or 4 via the Claisen-Schmidt reaction. The corresponding enantiomers of 5 and 6 were obtained in > 99% optical purity from the optical isomers of 4, resolved with the 0,0'-dibenzoyltartaric acids. The absolute configurations of the enantiomers of 4 were determined by conversion, via Clemmensen reduction, to the enantiomers of 1, the configurations of which are known. The determination of the regioisomer and configurational isomer of 5, with respect to the introduced benzylidene group, was determined from a single-crystal X-ray analysis. H-1 NMR data was used to confirm that 6 possessed the same configuration as 5. Radioreceptor binding studies in rat and guinea pig brain preparations revealed that (-)-(1S,5S)-5 displayed an 11-fold decrease in affinity for the opioid mu receptor and an increase in affinity for a receptors of 81-fold (low nanomolar affinity) relative to the ketone precursor (+)-(1S,5S)-4. An analogous, albeit less dramatic, trend was seen with compound (-)-(1S,5S)-6. Compounds (-)-(1S,5S)-5 and (-)-(1S,5S)-6 are distinct from the typical a-opiates in that they have very low affinity for either PCP sites or muscarinic receptors. The high affinity and selectivity of these novel a receptor ligands suggests that they will be valuable for the elucidation of the functional roles of sigma receptors. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NR 62 TC 16 Z9 17 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 16 PY 1994 VL 37 IS 19 BP 3163 EP 3170 DI 10.1021/jm00045a022 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PH073 UT WOS:A1994PH07300022 PM 7932540 ER PT J AU FERNICOLA, DJ ROBERTS, WC AF FERNICOLA, DJ ROBERTS, WC TI PURE MITRAL REGURGITATION ASSOCIATED WITH A MALFUNCTIONING CONGENITALLY BICUSPID AORTIC-VALVE NECESSITATING COMBINED MITRAL AND AORTIC-VALVE REPLACEMENT SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID ACTIVE INFECTIVE ENDOCARDITIS; NECROPSY PATIENTS; PROLAPSE; DYSFUNCTION C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 17 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1994 VL 74 IS 6 BP 619 EP 624 DI 10.1016/0002-9149(94)90758-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PF094 UT WOS:A1994PF09400020 PM 8074052 ER PT J AU LITTLE, RE LAMBERT, MD WORTHINGTONROBERTS, B ERVIN, CH AF LITTLE, RE LAMBERT, MD WORTHINGTONROBERTS, B ERVIN, CH TI MATERNAL SMOKING DURING LACTATION - RELATION TO INFANT SIZE AT ONE-YEAR OF AGE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BODY MASS INDEX; BREAST FEEDING; GROWTH; INFANT; LACTATION; SMOKING ID PASSIVE SMOKING; POST-PARTUM; PREGNANCY; GROWTH; CHILDREN; ALCOHOL; CAFFEINE; EXPOSURE; TOBACCO; MILK AB This study was conducted to test the hypothesis that breast-fed infants of smokers are smaller in size at 1 year of age than breast-fed infants of nonsmokers. Three groups of infants were selected from all singletons born to women who were seen for prenatal care in their 6th month of pregnancy at a health maintenance organization in Seattle, Washington, between January 1982 and April 1983. Breast-fed infants of smokers (n = 74) were compared with breast-fed infants of nonsmokers (n = 195) and with bottle-fed infants of smokers (n = 64). Mothers were interviewed at 1 and 3 months after delivery; both the mother and the infant were seen at 1 year. Among breast feeders, smokers' infants were twice as likely as nonsmokers' infants to have body mass more than 1 standard deviation above the mean (relative risk = 2.04, 95% confidence interval 1.15-3.61). This relation persisted after control for gestational age and weight at birth, length of lactation, mother's size and diet, exposure to other drugs in breast milk, and all other variables measured in this study. Every 10 cigarettes smoked while breast feeding predicted an additional 3% infant body mass at 1 year. In summary, breast-fed infants of smokers in this study gained more weight after birth than the other two groups; at 1 year of age, they were heavier and had significantly higher body mass. Reasons for this paradoxical finding are explored. C1 UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT,SEATTLE,WA. UNIV WASHINGTON,SCH PUBL HLTH,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,CTR CHILD DEV & MENTAL RETARDAT,SEATTLE,WA. RP LITTLE, RE (reprint author), NIEHS,EPIDEMIOL BRANCH,A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NICHD NIH HHS [HD14689] NR 19 TC 22 Z9 22 U1 1 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 544 EP 554 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600007 PM 8067348 ER PT J AU SPERDUTO, RD PODGER, MJ HILLER, R FREIDLIN, V MILTON, RC WOLF, PA MYERS, RH DAGOSTINO, RB ROSEMAN, MJ STOCKMAN, ME WILSON, PWF AF SPERDUTO, RD PODGER, MJ HILLER, R FREIDLIN, V MILTON, RC WOLF, PA MYERS, RH DAGOSTINO, RB ROSEMAN, MJ STOCKMAN, ME WILSON, PWF TI FAMILIAL AGGREGATION OF LENS OPACITIES - THE FRAMINGHAM EYE STUDY AND THE FRAMINGHAM OFFSPRING EYE STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CATARACT; GENETICS; MODELS, STATISTICAL ID CORRELATED BINARY REGRESSION; MODELS; EPIDEMIOLOGY; CATARACTS AB Eye examination data from 1,086 parents examined in the Framingham Eye Study (1973-1975) and 896 offspring examined in the Framingham Offspring Eye Study (1989-1991) were used to study familial associations for nuclear, cortical, and posterior subcapsular lens opacities. Associations between spouses, between parents and offspring, and between siblings were explored. The generalized estimating equations (GEE2) approach to logistic regression was used to simultaneously model risk of lens opacity and familial associations. Specifically, this provided odds ratios, adjusted for age (the age range was 50-74 years) and sex, for the familial associations. For any pair of siblings, the odds of nuclear opacity for one sibling was estimated to more than triple if the other sibling had a nuclear opacity. Similar findings were noted for posterior subcapsular opacity. No significant associations were noted for any of the opacity types between spouses or between parents and offspring. The strong associations between siblings for nuclear and posterior subcapsular opacities suggest there is clustering of lens opacities within families. The clustering may be due to genetic or environmental factors. C1 NEI, DIV BIOMETRY & EPIDEMIOL, BETHESDA, MD 20892 USA. BOSTON UNIV, BOSTON, MA 02215 USA. NHLBI, FRAMINGHAM, MA USA. NR 18 TC 30 Z9 30 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 555 EP 564 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600008 ER PT J AU WEINBERG, CR UMBACH, DM GREENLAND, S AF WEINBERG, CR UMBACH, DM GREENLAND, S TI WHEN WILL NONDIFFERENTIAL MISCLASSIFICATION OF AN EXPOSURE PRESERVE THE DIRECTION OF A TREND SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BIAS (EPIDEMIOLOGY); BIOMETRY; EPIDEMIOLOGIC METHODS ID DIFFERENTIAL MISCLASSIFICATION; ALWAYS BIAS; NULL VALUE; ERRORS AB Dosemeci et al. (Am J Epidemiol 1990;132:756-8) gave examples in which nondifferential misclassification of exposure reversed the direction of a trend. Gilbert (Am J Epidemiol 1991;134:440-1) proposed that these examples occurred because the errors in exposure were systematic, and she pointed out that the relation between the measured and the true exposure was not monotonic. Assuming that the mean response either monotonically increases or decreases with the true exposure and that the exposure misclassification is nondifferential, the authors show that if the mean value of the measured exposure increases with the true exposure, then the direction of the trend cannot be reversed. Consequently, gilberts intimation that reversal of trend can only occur when errors are systematic is correct. However, the present authors' result is stronger in that even when errors in assessing exposure do not include a systematic component, if monotonicity can be assumed, reversal of trend cannot occur. The weaker condition of positive correlation between the measured and true exposure in not sufficient to guarantee nonreferral of trend, as they show by example. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. RP WEINBERG, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 15 TC 50 Z9 52 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 565 EP 571 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600009 PM 8067350 ER PT J AU BRAUN, MM CAPORASO, NE BRINTON, L AF BRAUN, MM CAPORASO, NE BRINTON, L TI RE - TWIN MEMBERSHIP AND BREAST-CANCER RISK SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP BRAUN, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20852, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 6 TC 7 Z9 7 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 575 EP 576 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600010 PM 8067351 ER PT J AU FRIEDENREICH, CM HOWE, GR MILLER, AB AF FRIEDENREICH, CM HOWE, GR MILLER, AB TI RE - A COMPARISON OF PROSPECTIVE AND RETROSPECTIVE ASSESSMENTS OF DIET IN THE STUDY OF BREAST-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID RECALL BIAS; ASSOCIATION C1 UNIV TORONTO,NCI,EPIDEMIOL UNIT,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,DEPT PREVENT MED & BIOSTAT,TORONTO M5S 1A8,ON,CANADA. RP FRIEDENREICH, CM (reprint author), UNIV CALGARY,DEPT COMMUNITY HLTH SCI,CALGARY T2N 4N1,AB,CANADA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 579 EP 580 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600015 PM 8067354 ER PT J AU URSIN, G ZIEGLER, RG HOOVER, R HAILE, RW SUBAR, AF GRAUBARD, B AF URSIN, G ZIEGLER, RG HOOVER, R HAILE, RW SUBAR, AF GRAUBARD, B TI RE - DIETARY PATTERNS ASSOCIATED WITH A LOW-FAT DIET IN THE NATIONAL-HEALTH EXAMINATION FOLLOW-UP-STUDY - IDENTIFICATION OF POTENTIAL CONFOUNDERS FOR EPIDEMIOLOGIC ANALYSES AND TOWARD A CLEARER DEFINITION OF CONFOUNDING - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP URSIN, G (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033, USA. NR 5 TC 0 Z9 0 U1 0 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 582 EP 583 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600018 ER PT J AU WEINBERG, CR AF WEINBERG, CR TI RE - DIETARY PATTERNS ASSOCIATED WITH A LOW-FAT DIET IN THE NATIONAL-HEALTH EXAMINATION FOLLOW-UP-STUDY - IDENTIFICATION OF POTENTIAL CONFOUNDERS FOR EPIDEMIOLOGIC ANALYSES AND TOWARD A CLEARER DEFINITION OF CONFOUNDING - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP WEINBERG, CR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1994 VL 140 IS 6 BP 583 EP 584 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PG136 UT WOS:A1994PG13600019 ER PT J AU FREID, KM ANTON, K AF FREID, KM ANTON, K TI GROWTH-HORMONE AS AN ADJUNCT TO PARENTERAL-NUTRITION SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID FACTOR-I; PROTEIN; SUPPORT; OPERATION C1 NIH,CTR CLIN,BETHESDA,MD 20892. NIH,DRUG INFORMAT SERV,BETHESDA,MD 20892. RP FREID, KM (reprint author), GRANT MED CTR,COLUMBUS,OH 43215, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD SEP 15 PY 1994 VL 51 IS 18 BP 2244 EP & PG 0 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PH671 UT WOS:A1994PH67100003 PM 7801985 ER PT J AU DETERAWADLEIGH, SD HSIEH, WT BERRETTINI, WH GOLDIN, LR ROLLINS, DY MUNIEC, D GREWAL, R GUROFF, JJ TURNER, G COFFMAN, D BARRICK, J MILLS, K MURRAY, J DONOHUE, SJ KLEIN, DC SANDERS, J NURNBERGER, JI GERSHON, ES AF DETERAWADLEIGH, SD HSIEH, WT BERRETTINI, WH GOLDIN, LR ROLLINS, DY MUNIEC, D GREWAL, R GUROFF, JJ TURNER, G COFFMAN, D BARRICK, J MILLS, K MURRAY, J DONOHUE, SJ KLEIN, DC SANDERS, J NURNBERGER, JI GERSHON, ES TI GENETIC-LINKAGE MAPPING FOR A SUSCEPTIBILITY LOCUS TO BIPOLAR ILLNESS - CHROMOSOME-2, CHROMOSOME-3, CHROMOSOME-4, CHROMOSOME-7, CHROMOSOME-9, CHROMOSOME-10P, CHROMOSOME-11P, CHROMOSOME-22, AND CHROMOSOME-XPTER SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE MANIC-DEPRESSIVE; POLYMORPHISM; GENOTYPE; DOMINANT MODEL ID MANIC-DEPRESSIVE ILLNESS; OLD ORDER AMISH; AFFECTIVE-DISORDER; COMPLEMENTARY-DNA; PEDIGREES; RECEPTOR; MARKERS; SEARCH; DISEASE; COMPLEX AB We are conducting a genome search for a predisposing locus to bipolar (manic-depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than -2 at Theta = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at Theta = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage but for PLANH1, at the weighting functions f(p)=1 and f(p)=1/sqrt(p) borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralocorticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of <-2 at Theta = 0.01 were found. (C) 1994 Wiley-Liss, Inc. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT,PHILADELPHIA,PA 19107. UNIV IOWA,DEPT PEDIAT,IOWA CITY,IA 52242. UNIV HOUSTON,SCH MED,HOUSTON,TX. INDIANA UNIV,MED CTR,INST PSYCHIAT RES,INDIANAPOLIS,IN. RP DETERAWADLEIGH, SD (reprint author), NIMH,NICHHD,CLIN NEUROGENET BRANCH,BLDG 10,RM 3N218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 45 Z9 45 U1 2 U2 2 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 SEP 15 PY 1994 VL 54 IS 3 BP 206 EP 218 DI 10.1002/ajmg.1320540307 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA PE378 UT WOS:A1994PE37800006 PM 7810578 ER PT J AU WOODAGE, T DENG, ZM PRASAD, M SMART, R LINDEMAN, R CHRISTIAN, SL LEDBETTER, DH ROBSON, L SMITH, A TRENT, RJ AF WOODAGE, T DENG, ZM PRASAD, M SMART, R LINDEMAN, R CHRISTIAN, SL LEDBETTER, DH ROBSON, L SMITH, A TRENT, RJ TI A VARIETY OF GENETIC MECHANISMS ARE ASSOCIATED WITH THE PRADER-WILLI-SYNDROME SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE PRADER-WILLI SYNDROME; CHROMOSOME 15; GENETIC IMPRINTING; CHROMOSOMAL DELETION; UNIPARENTAL DISOMY ID DINUCLEOTIDE REPEAT POLYMORPHISM; UNIPARENTAL DISOMY; CRITICAL REGION; D15S11 LOCUS; PROXIMAL 15Q; LINKAGE MAP; ANGELMAN; CHROMOSOME-15; DELETIONS; ORIGIN AB An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis with four markers mapping to the Prader-Willi chromosome region (PWCR) of chromosome 15 have been used to characterize a cohort of 30 subjects with classical Prader-Willi syndrome (PWS). Molecular analysis enabled the classification of the PWS subjects into four groups: (A) 18 subjects (60%) had deletions of paternal 15q11-13 involving a common set of DNA markers. Two subjects had differently sized deletions, one larger and one smaller than the other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15. (C) One (3%) had a marker chromosome carrying an extra copy of the PWCR. The marker chromosome was demonstrated to be of paternal origin and the two intact chromosomes were maternally derived. This case represents an apparent exception to the generally held view that PWS is associated with an absence of paternally inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had none of the above abnormalities. This last subgroup of patients has not previously been well characterized but could represent limited deletions not detectable with the markers used or abnormalities in the imprinting process. These cases represent potentially valuable resources to elucidate more precisely the fundamental disorders responsible for PWS. (C) 1994 Wiley-Liss, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. CHILDRENS HOSP,DEPT MED GENET,CAMPERDOWN,NSW,AUSTRALIA. RP WOODAGE, T (reprint author), ROYAL PRINCE ALFRED HOSP,DEPT MOLEC GENET,MISSENDEN RD,CAMPERDOWN 2050,NSW,AUSTRALIA. NR 39 TC 30 Z9 30 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 15 PY 1994 VL 54 IS 3 BP 219 EP 226 DI 10.1002/ajmg.1320540308 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA PE378 UT WOS:A1994PE37800007 PM 7810579 ER PT J AU PERKINS, JR TOMER, KB AF PERKINS, JR TOMER, KB TI CAPILLARY ELECTROPHORESIS ELECTROSPRAY MASS-SPECTROMETRY USING A HIGH-PERFORMANCE MAGNETIC-SECTOR MASS-SPECTROMETER SO ANALYTICAL CHEMISTRY LA English DT Article ID ELECTROSPRAY IONIZATION INTERFACE; ZONE ELECTROPHORESIS; NAJA-MELANOLEUCA; LIQUID-JUNCTION; PROTEINS; PEPTIDES; SEPARATION; VENOM; BIOMOLECULES; CONJUNCTION AB Capillary electrophoresis/electrospray mass spectrometry using a high-performance magnetic sector mass spectrometer has been performed with both bare fused silica and 3-(aminopropyl)trimethoxysilane-derivatized silica columns for simple peptide mixtures and for a snake venom. The latter is essentially a naturally occurring complex mixture of small proteins. Adaptation of the existing electrospray system to accommodate capillary electrophoresis methodologies was extremely simple. Full-scan CE/MS on a sector mass spectrometer combined sensitivity with high resolution for discrimination between species of similar mass to charge ratios. C1 KRATOS ANALYT,MANCHESTER M31 2LD,LANCS,ENGLAND. NIEHS,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 46 TC 34 Z9 34 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 15 PY 1994 VL 66 IS 18 BP 2835 EP 2840 DI 10.1021/ac00090a008 PG 6 WC Chemistry, Analytical SC Chemistry GA PG636 UT WOS:A1994PG63600011 ER PT J AU LEBEAU, MC MYAGKIKH, I ROUVIEREFOURMY, N BAULIEU, EE KLEE, CB AF LEBEAU, MC MYAGKIKH, I ROUVIEREFOURMY, N BAULIEU, EE KLEE, CB TI RABBIT FKBP-59/HBI DOES NOT INHIBIT CALCINEURIN ACTIVITY IN-VITRO SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEAT-SHOCK PROTEIN; STEROID-RECEPTOR COMPLEXES; CIS-TRANS ISOMERASE; CYCLOSPORINE-A; LYMPHOCYTES-T; LIMITED PROTEOLYSIS; BINDING PROTEIN; IMMUNOPHILIN; FK506; FK-506 AB The effect of recombinant FKBP-59/HBI or of its first N-terminal domain FKBP-59/HBI-I on the phosphatase activity of calcineurin (a Ca+2-calmodulin dependent phosphatase) was tested in vitro in the presence or absence of the immunosuppressant drug FK506. Contrarily to the inhibition observed with the immunosuppressant complex FKBP-12-FK506, no significant inhibition was observed with FKBP59/HBI or FKBP-59/HBI-I in the presence of FK506, even though FKBP-59/HBI-1 is nearly 55% homologous to the immunophilin FKBP-12. Inhibition was rested both with native calcineurin (calcineurin A: Mr 58-59 kDa) and with protease activated, calmodulin independent calcineurin (calcineurin A: Mr 45 kDa). There was no competitive effect of FKBP-59 on the inhibitory activity of the FKBP-12-FK506 complex, even when the molar concentration of FKBP-59/HBI was 100 times higher than that of FKBP-12. Clearly, although the first domain of FKBP-59/HBI displays several structural and functional features of FKBP-12, it does not interact with calcineurin. (C) 1994 Academic Press, Inc. C1 NCI,BETHESDA,MD 20892. RP LEBEAU, MC (reprint author), INSERM,U33,80 RUE GEN LECLERC,F-94276 LE KREMLIN BICETR,FRANCE. NR 26 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 15 PY 1994 VL 203 IS 2 BP 750 EP 755 DI 10.1006/bbrc.1994.2246 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PG801 UT WOS:A1994PG80100002 PM 7522447 ER PT J AU VORCE, RL LEE, B HOWARD, BH AF VORCE, RL LEE, B HOWARD, BH TI METHYLATION-DEPENDENT AND MUTATION-DEPENDENT STIMULATION OF ALU TRANSCRIPTION IN-VITRO SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA METHYLATION; REPEATED SEQUENCES; INHIBITS TRANSCRIPTION; POLYMERASE-III; SOURCE GENES; RNA; FAMILY; SUBFAMILIES; EXPRESSION; REPRESSION AB Alu genes are GC-rich, highly repetitive genetic elements whose functions remain unknown. Members of this family are readily transcribed in vitro by RNA polymerase III, but RNA corresponding to only a small sub-set of Alu elements has been found in vivo. Based on the hypothesis that methylation of Alu elements affects their transcription, the transcriptional activity of unmethylated and methylated template DNA was assessed in vitro. It was found that methylation of a single CG site just 5' to Alu functions to stimulate transcription; the base composition in this region also affects transcriptional activity. These results indicate that the methylation state and sequence of DNA flanking Alu elements influence its transcription rate. (C) 1994 Academic Press, Inc. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD. NR 29 TC 7 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 15 PY 1994 VL 203 IS 2 BP 845 EP 851 DI 10.1006/bbrc.1994.2260 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PG801 UT WOS:A1994PG80100016 PM 8093066 ER PT J AU LETEURTRE, F KOHLHAGEN, G POMMIER, Y AF LETEURTRE, F KOHLHAGEN, G POMMIER, Y TI STREPTONIGRIN-INDUCED TOPOISOMERASE-II SITES EXHIBIT BASE PREFERENCES IN THE MIDDLE OF THE ENZYME STAGGER SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DRUG-INTERACTION DOMAINS; MEDIATED DNA CLEAVAGE; C-MYC; EUKARYOTIC TOPOISOMERASE; SEQUENCE REQUIREMENTS; CAMPTOTHECIN; BINDING; PROTEIN; IDENTIFICATION; RECOGNITION AB The non DNA intercalator streptonigrin was shown to inhibit topoisomerase II by stabilizing cleavable complexes (Yamashita et al, Cancer Res. 1990, 50, 5841). Streptonigrin-induced topoisomerase II cleavage sites were mapped in the c-myc proto-oncogene DNA. Streptonigrin induced a unique cleavage pattern. Its cleavage sites were less frequent than those induced by other topoisomerase II inhibitors. Strongly preferred bases were found in the middle of topoisomerase II DNA stagger, with thymine at position +2 and adenine at position +3, position +1 being the nucleotide covalently linked to topoisomerase II. Preference for bases not immediately flanking the cleavage sites has not been reported previously and indicates that a mechanism other than ''drug stacking'' within the DNA break is taking place with streptonigrin to stabilize cleavable complexes. An alternative model taking into account the unusual DNA binding properties of streptonigrin is proposed. (C) 1994 Academic Press, Inc. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 37 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 15 PY 1994 VL 203 IS 2 BP 1259 EP 1267 DI 10.1006/bbrc.1994.2318 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PG801 UT WOS:A1994PG80100074 PM 8093042 ER PT J AU KISS, Z TOMONO, M ANDERSON, WB AF KISS, Z TOMONO, M ANDERSON, WB TI PHORBOL EATER SELECTIVELY STIMULATES THE PHOSPHOLIPASE D-MEDIATED HYDROLYSIS OF PHOSPHATIDYLETHANOLAMINE IN MULTIDRUG-RESISTANT MCF-7 HUMAN BREAST-CARCINOMA CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; RAT MESANGIAL CELLS; PHOSPHATIDIC-ACID FORMATION; NIH 3T3 FIBROBLASTS; DRUG-RESISTANCE; GROWTH-FACTOR; P-GLYCOPROTEIN; PHOSPHATIDYLCHOLINE BREAKDOWN; ULTRASTRUCTURAL ALTERATIONS; PLASMA-MEMBRANES AB The phospholipase D (PLD)-mediated synthesis of phosphatidylethanol (PtdEtOH) and the hydrolysis of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) were examined in drug-sensitive and multidrug-resistant lines of MCF-7 human breast carcinoma cells. In drug-sensitive (MCF-7/WT) cells, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) failed to enhance either the synthesis of PtdEtOH or the hydrolysis of either phospholipid. In the drug-resistant (MCF-7/MDR) cells, 100 nM PMA greatly enhanced both the synthesis of PtdEtOH (similar to 21-fold) and the hydrolysis of PtdEtn (similar to 29-fold), but had no effect on the hydrolysis of PtdCho. The PLD activators sphingosine and H2O2 were found to elicit only a slight (1.28-1.4-fold) stimulatory effect on PtdCho hydrolysis in both the MCF-7/WT and MCF-7/MDR cell types, and had only a small effect on PtdEtn hydrolysis in the MCF-7/WT cells as well. However, these agents significantly (similar to 2.6-3.5-fold) stimulated PtdEtn hydrolysis in the MCF-7/ MDR cells. These data indicate that MCF-7/MDR cells contain a PtdEtn-specific PLD activity which can be selectively stimulated by PMA, sphingosine and H2O2. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. RP KISS, Z (reprint author), UNIV MINNESOTA,HORMEL INST,801 16TH AVE NE,AUSTIN,MN 55912, USA. NR 56 TC 29 Z9 29 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 SEP 15 PY 1994 VL 302 BP 649 EP 654 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PJ337 UT WOS:A1994PJ33700003 PM 7945188 ER PT J AU BURNETT, D ADAMS, DH MARTIN, TJM LIU, Q GRANT, RA STOCKLEY, RA LORD, JM AF BURNETT, D ADAMS, DH MARTIN, TJM LIU, Q GRANT, RA STOCKLEY, RA LORD, JM TI INHIBITION BY FK506 OF FORMYL PEPTIDE-INDUCED NEUTROPHIL ACTIVATION AND ASSOCIATED PROTEIN-SYNTHESIS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE FORMYL-PEPTIDE; RECEPTOR; IMMUNOPHILIN; SIGNALING ID CALCINEURIN PHOSPHATASE-ACTIVITY; T-CELL ACTIVATION; CYCLOSPORINE-A; IMMUNOSUPPRESSANT FK506; SIGNAL TRANSDUCTION; ALLOGRAFT-REJECTION; INDUCED ARTHRITIS; LYMPHOCYTES-T; FK-506; COMPLEXES AB The macrolide FK506 inhibited, by up to 50%, neutrophil migration and the production of the superoxide radical in response to the formyl peptide, formyl-methionyl-leucyl-phenylalanine (FMLP). The production of the superoxide radical in response to phorbol 12-myristate 13-acetate (PMA) was unaffected by FK506. The inhibition of neutrophil functions was accompanied by a partial reversal of FMLP-induced synthesis of cellular proteins, despite a rise in intracellular Ca2+. Neutrophils treated with FK506 demonstrated a small (average 23%) though significant decrease in formyl-peptide receptor numbers but receptor binding affinity was unaffected. The effects of FK506 on neutrophil activation appear to be analogous to those in T-lymphocytes. The incomplete inhibition, by FK506, of neutrophil responses suggests further that activation by FMLP is mediated via distinct multiple signalling pathways, including protein kinase activation and protein synthesis. The inability of FK506 to reduce FMLP-induced rises in cellular Ca2+ or PMA-induced activation of neutrophils suggests that its action is distal to Ca2+ mobilization and distinct from pathways relying on PKC activation. Thus the immunosuppressive effects of FK506 in vivo might be mediated through the inhibition of inflammatory cells other than lymphocytes and the drug therefore has therapeutic potential in a variety of inflammatory conditions. The drug also has potential in vitro for the characterization of signalling pathways from the plasma membrane to the nucleus. C1 GEN HOSP,CLIN TEACHING BLOCK,LUNG IMMUNOBIOCHEM RES LAB,BIRMINGHAM,W MIDLANDS,ENGLAND. UNIV BIRMINGHAM,DEPT MED,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. QUEEN ELIZABETH HOSP,LIVER UNIT,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD. RP BURNETT, D (reprint author), UNIV BIRMINGHAM,SCH MED,DEPT IMMUNOL,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. FU Wellcome Trust NR 42 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 15 PY 1994 VL 48 IS 6 BP 1081 EP 1088 DI 10.1016/0006-2952(94)90143-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ959 UT WOS:A1994PJ95900003 PM 7524504 ER PT J AU SZIGETHY, E CONWELL, Y FORBES, NT COX, C CAINE, ED AF SZIGETHY, E CONWELL, Y FORBES, NT COX, C CAINE, ED TI ADRENAL WEIGHT AND MORPHOLOGY IN VICTIMS OF COMPLETED SUICIDE SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADRENAL; WEIGHT; MORPHOLOGY; SUICIDE; DEPRESSION; HPA AXIS ID DEXAMETHASONE SUPPRESSION TEST; CORTICOTROPIN-RELEASING HORMONE; DEPRESSED-PATIENTS; MAJOR DEPRESSION; ADRENOCORTICAL FUNCTION; ENDOGENOUS-DEPRESSION; COMPUTED-TOMOGRAPHY; HEALTHY-VOLUNTEERS; IMIPRAMINE BINDING; CORTISOL-LEVELS AB Several lines of evidence have implicated hypothalamic-pituitary-adrenal (HPA) axis dysfunction in major depression and suicidal behavior. In the present study the weight and morphology of postmortem adrenal glands were compared between suicide victims and sudden death, nonpsychiatric controls. The mean adrenal weight of the combined left and right glands was significantly higher in the suicide group; this difference was accounted for specifically by increases in left adrenal weight of suicides compared with the control group. There was a positive correlation between adrenal weight and total cortical thickness in both left and right glands, providing direct evidence that increased adrenal weight in suicide victims is due to cortical hypertrophy. The finding of left-right adrenal weight asymmetry in suicides is consistent with the hypothesis of abnormal lateralized input from higher control centers of the HPA axis. C1 UNIV ROCHESTER,MED CTR,SCH MED,ROCHESTER,NY 14642. UNIV ROCHESTER,NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,DEPT PSYCHIAT,ROCHESTER,NY. UNIV ROCHESTER,NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,DEPT BIOSTAT,ROCHESTER,NY. OFF MED EXAMINER MONROE CTY,ROCHESTER,NY. RI Szigethy, Eva/I-7860-2013 FU NIMH NIH HHS [MH40381] NR 72 TC 61 Z9 61 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1994 VL 36 IS 6 BP 374 EP 380 DI 10.1016/0006-3223(94)91212-2 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PJ338 UT WOS:A1994PJ33800004 PM 7803598 ER PT J AU FOSS, FM BORKOWSKI, TA GILLIOM, M STETLERSTEVENSON, M JAFFE, ES FIGG, WD TOMPKINS, A BASTIAN, A NYLEN, P WOODWORTH, T UDEY, MC SAUSVILLE, EA AF FOSS, FM BORKOWSKI, TA GILLIOM, M STETLERSTEVENSON, M JAFFE, ES FIGG, WD TOMPKINS, A BASTIAN, A NYLEN, P WOODWORTH, T UDEY, MC SAUSVILLE, EA TI CHIMERIC FUSION PROTEIN TOXIN DAB(486) IL-2 IN ADVANCED MYCOSIS-FUNGOIDES AND THE SEZARY-SYNDROME - CORRELATION OF ACTIVITY AND INTERLEUKIN-2 RECEPTOR EXPRESSION IN A PHASE-II STUDY SO BLOOD LA English DT Article ID T-CELL LYMPHOMA; IL-2 RECEPTOR; TRIAL; DAB486IL-2; TAC; CHEMOTHERAPY; MALIGNANCIES; DISORDERS; LEUKEMIA; ANTIGENS AB DAB(486)IL-2 is a recombinant toxin with the cell surface-binding domain of diphtheria toxin (DT) replaced by interleukin-2 (IL-2). To correlate clinical response with expression of components of the IL-2 receptor (IL-2R), 14 patients with cutaneous T-cell lymphoma (CTCL) received five daily 90-minute infusions every 21 days. There were no complete responses, 1 partial response (PR), 2 major biologic effects (major cutaneous improvement without change in circulating neoplastic cells), 3 stable disease (SD), and 8 progressive disease (PD). Responders had easily detected expression of CD25 (Tac; alpha-chain of IL-2R) in skin, and in two responders expression of the beta chain of the IL-2 receptor (beta-IL-SR) was detectable by reverse transcriptase-polymerase chain reaction. CD25 was also detected in 8 of 11 SD or PD patients, with beta-IL-2R in 3 of 8 SD or PD patients. Two of the three responders had anti-DT antibodies before treatment. Reversible increased hepatic transaminases occurred in 13 of 14 patients during the first course, with decreased frequency in repeated courses. The maximal serum concentration after the first infusion of DAB(486)IL-2 varied (1,369 +/- 1,155 ng/mL [mean +/- SD]; n = 14; range, 55 to 3,999 ng/mL) with a short half-life (T(1/2)beta = 0.21 +/- 0.12 h [mean +/- SD]; range, 0.099 to 0.57 h). The area under the concentration curve varied inversely with anti-DT antibody titer. We conclude that DAB(486)IL-2 has valuable activity in certain patients with CTCL. Expression of the IL-2R may be necessary but is not sufficient to predict response. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. USN HOSP,BETHESDA,MD. SERAGEN INC,HOPKINTON,MA. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 41 TC 61 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 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1994 VL 84 IS 6 BP 1765 EP 1774 PG 10 WC Hematology SC Hematology GA PG388 UT WOS:A1994PG38800009 PM 8080984 ER PT J AU DAWSEY, SM LEWIN, KJ WANG, GQ LIU, FS NIEBERG, RK YU, Y LI, JY BLOT, WJ LI, B TAYLOR, PR AF DAWSEY, SM LEWIN, KJ WANG, GQ LIU, FS NIEBERG, RK YU, Y LI, JY BLOT, WJ LI, B TAYLOR, PR TI SQUAMOUS ESOPHAGEAL HISTOLOGY AND SUBSEQUENT RISK OF SQUAMOUS-CELL CARCINOMA OF THE ESOPHAGUS - A PROSPECTIVE FOLLOW-UP-STUDY FROM LINXIAN, CHINA SO CANCER LA English DT Article DE ESOPHAGUS; ESOPHAGEAL NEOPLASMS; PRECANCEROUS CONDITIONS; ENDOSCOPY; PATHOLOGY; SQUAMOUS DYSPLASIA; SQUAMOUS CELL CARCINOMA; FOLLOW-UP STUDIES ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; PRECURSOR LESIONS; CANCER INCIDENCE; DYSPLASIA; POPULATIONS; SUPPLEMENTATION; EPITHELIUM; IRAN AB Background. Linxian, China, has some of the highest rates of esophageal cancer in the world. Previous authors have proposed that esophagitis, atrophy, and dysplasia may be precursor lesions of esophageal cancer in such high risk populations. Methods. To examine the relationship between squamous esophageal histology and subsequent esophageal cancer in Linxian, the authors prospectively followed 682 participants of a 1987 endoscopic survey for 3.5 years and compared their initial biopsy diagnoses with the occurrence of squamous cell carcinoma during this follow-up period. Results. Squamous cell carcinoma of the esophagus was identified in 52 (7.6%) of the participants during the follow-up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for squamous cell carcinoma incidence by initial histologic diagnoses were as follows: normal, 1.0 (reference); basal cell hyperplasia, 2.1 (0.4-9.8); mild dysplasia, 2.2 (0.7-7.5); moderate dysplasia, 15.8 (5.9-42.2); severe dysplasia, 72.6 (29.8-176.9); dysplasia not otherwise specified, 22.9 (6.7-78.0); and carcinoma in situ, 62.5 (24.1-161.9). Conclusion. In this study, moderate dysplasia, severe dysplasia, and carcinoma in situ were the only histologic lesions associated with a significantly increased risk of developing squamous cell carcinoma of the esophagus within 3.5 years after endoscopy. Increasing grades of dysplasia were associated with increasing risk, but severe dysplasia and carcinoma in situ had similar degrees of risk, findings that suggest a continuous spectrum of esophageal intraepithelial neoplasia, without morphologically distinguishable dysplasia and in situ carcinoma. A longer follow-up will be necessary to fully evaluate the less severe diagnostic categories, which may take more than 3.5 years to affect the occurrence of squamous cell carcinoma in this high risk population. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90024. CHINESE ACAD MED SCI,INST CANC,DEPT CHEST SURG,BEIJING 100021,PEOPLES R CHINA. CHINESE ACAD MED SCI,INST CANC,DEPT PATHOL,BEIJING 100021,PEOPLES R CHINA. CHINESE ACAD MED SCI,INST CANC,DEPT EPIDEMIOL,BEIJING 100021,PEOPLES R CHINA. CHINA CANC RES FDN,BEIJING,PEOPLES R CHINA. RP DAWSEY, SM (reprint author), NCI,CANC PREVENT STUDIES BRANCH,EXEC PLAZA N,ROOM 211,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-05634, N01-CP-95616] NR 24 TC 105 Z9 126 U1 1 U2 4 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 SEP 15 PY 1994 VL 74 IS 6 BP 1686 EP 1692 DI 10.1002/1097-0142(19940915)74:6<1686::AID-CNCR2820740608>3.0.CO;2-V PG 7 WC Oncology SC Oncology GA PG098 UT WOS:A1994PG09800007 PM 8082069 ER PT J AU GREENBLATT, MS BENNETT, WP HOLLSTEIN, M HARRIS, CC AF GREENBLATT, MS BENNETT, WP HOLLSTEIN, M HARRIS, CC TI MUTATIONS IN THE P53 TUMOR-SUPPRESSOR GENE - CLUES TO CANCER ETIOLOGY AND MOLECULAR PATHOGENESIS SO CANCER RESEARCH LA English DT Review ID CELL LUNG-CANCER; HEPATITIS-B VIRUS; STRAND CONFORMATION POLYMORPHISM; HUMAN HEPATOCELLULAR CARCINOMAS; DENATURANT GEL-ELECTROPHORESIS; UPPER AERODIGESTIVE TRACT; XERODERMA-PIGMENTOSUM PATIENTS; HUMAN-MALIGNANT MELANOMA; HAMSTER OVARY CELLS; MURINE SKIN TUMORS C1 NCI, DIV CANC ETIOL, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. GERMAN CANC RES CTR, DIV TOXICOL, D-69120 HEIDELBERG, GERMANY. NR 287 TC 3176 Z9 3251 U1 27 U2 117 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1994 VL 54 IS 18 BP 4855 EP 4878 PG 24 WC Oncology SC Oncology GA PF791 UT WOS:A1994PF79100007 PM 8069852 ER PT J AU BEUSCHLEIN, F REINCKE, M KARL, M TRAVIS, WD JAURSCHHANCKE, C ABDELHAMID, S CHROUSOS, GP ALLOLIO, B AF BEUSCHLEIN, F REINCKE, M KARL, M TRAVIS, WD JAURSCHHANCKE, C ABDELHAMID, S CHROUSOS, GP ALLOLIO, B TI CLONAL COMPOSITION OF HUMAN ADRENOCORTICAL NEOPLASMS SO CANCER RESEARCH LA English DT Article ID DEPENDENT CUSHINGS-SYNDROME; DISCOVERED ADRENAL MASS; HUMAN-TUMORS; LOCUS DXS255; METHYLATION; HYPERPLASIA; M27-BETA; ORIGIN AB The mechanisms of tumorigenesis of adrenocortical neoplasms are still not understood. Tumor formation may be the result of spontaneous transformation of adrenocortical cells by somatic mutations. Another factor stimulating adrenocortical cell growth and potentially associated with formation of adrenal adenomas and, less frequently, carcinomas is the chronic elevation of proopiomelanocortin-derived peptides in diseases like ACTH-dependent Cushing's syndrome and congenital adrenal hyperplasia. To further investigate the pathogenesis of adrenocortical neoplasms, we studied the clonal composition of such tumors using X-chromosome inactivation analysis of the highly polymorphic region Xcen-Xp11.4 with the hybridization probe M27 beta, which maps to a variable number of tandem repeats on the X-chromosome. In addition, polymerase chain reaction amplification of a phosphoglycerokinase gene polymorphism was performed. After DNA extraction from tumorous adrenal tissue and normal leukocytes in parallel, the active X-chromosome of each sample was digested with the methylation-sensitive restriction enzyme HpaII. A second digestion with an appropriate restriction enzyme revealed the polymorphism of the region Xcen-Xp11.4 and the phosphoglycerokinase locus. Whereas in normal polyclonal tissue both the paternal and maternal alleles are detected, a monoclonal tumor shows only one of the parental alleles. A total of 21 female patients with adrenal lesions were analyzed; 17 turned out to be heterozygous for at least one of the loci. Our results were as follows: diffuse (n = 4) and nodular (n = 1) adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome, polyclonal pattern; adrenocortical adenomas (n = 8), monoclonal (n = 7), as well as polyclonal (n = 1); adrenal carcinomas (n = 3), monoclonal pattern. One metastasis of an adrenocortical carcinoma showed a pattern most likely due to tumor-associated loss of methylation. In the special case of a patient with bilateral ACTH-independent macronodular hyperplasia, diffuse hyperplastic areas and a small nodule showed a polyclonal pattern, whereas a large nodule was monoclonal. We conclude that most adrenal adenomas and carcinomas are monoclonal, whereas diffuse and nodular adrenal hyperplasias are polyclonal. The clonal composition of ACTH-independent massive macronodular hyperplasia seems to be heterogeneous, consisting of polyclonal and monoclonal areas. C1 UNIV WURZBURG,MED KLIN,D-97080 WURZBURG,GERMANY. UNIV HAMBURG,INST HORMON & FERTILITATSFORSCH,HAMBURG,GERMANY. DEUTSCH KLIN DIAGNOST,W-6200 WIESBADEN,GERMANY. NCI,DEPT CLIN PATHOL,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 38 TC 107 Z9 107 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 SEP 15 PY 1994 VL 54 IS 18 BP 4927 EP 4932 PG 6 WC Oncology SC Oncology GA PF791 UT WOS:A1994PF79100015 PM 7915195 ER PT J AU SEKIDO, Y BADER, SA CARBONE, DP JOHNSON, BE MINNA, JD AF SEKIDO, Y BADER, SA CARBONE, DP JOHNSON, BE MINNA, JD TI MOLECULAR ANALYSIS OF THE HUD GENE ENCODING A PARANEOPLASTIC ENCEPHALOMYELITIS ANTIGEN IN HUMAN LUNG-CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article ID FREE DEFINED MEDIUM; SENSORY NEURONOPATHY; SEX-LETHAL; CIRCULATING ANTIBODIES; CLINICAL SPECIMENS; ONCOGENE PRODUCT; MESSENGER-RNAS; PROTEIN P53; DROSOPHILA; EXPRESSION AB Small cell lung cancer (SCLC) is known to express the HuD protein, the neuronal antigen homologous to Drosophila Elav and Sxl genes involved in neuronal and sex development. HuD is the target of an immune response including high titered antibodies causing paraneoplastic encephalomyelitis and sensory neuropathy. Because the p53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HuD antibodies signaled the presence of HuD mutations in lung cancer. The HuD gene was mapped to chromosome region 1p using a human-mouse hybrid cell panel. We confirmed that 26 of 46 cancer (43 lung cancer and 3 mesothelioma) cell lines expressed HuD mRNA and that this expression, as well as protein expression by Western blot, correlated strongly with the SCLC neuroendocrine phenotype. Southern blot and single-strand conformation polymorphism analyses showed that HuD was not mutated in 78 lung cancers, including patients with the severe paraneoplastic syndrome. Northern blot analysis showed that lung cancer cell lines expressed two major mRNAs (43 and 4.0 kilobases) of HuD. We found the three previously described alternative spliced mRNA forms (HuDpro, HuD, and HuDmex). In addition, we also found HuD mRNA had an alternative splicing form in its 5'-coding region This alternative splice introduced 87 base pairs of sequence and a termination codon resulting in a predicted small, truncated protein (11 amino acids) reminiscent of the male-specific truncated protein in the Sex-lethal (Sxl) gene of Drosophila. However, mRNAs encoding both full-length and truncated proteins were expressed in all SCLCs. These results show that the HuD gene is not mutated in lung cancer, including tumors from patients producing anti-HuD antibodies, but HuD expression is an independent marker or determinant of the neuroendocrine differentiation seen in SCLC. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DEPT INTERNAL MED,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DEPT PHARMACOL,DALLAS,TX 75235. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. RI Sekido, Yoshitaka/P-9756-2015 FU NCI NIH HHS [P 20 CA58220-01] NR 43 TC 47 Z9 47 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1994 VL 54 IS 18 BP 4988 EP 4992 PG 5 WC Oncology SC Oncology GA PF791 UT WOS:A1994PF79100024 PM 8069866 ER PT J AU KIM, WH SCHNAPER, HW NOMIZU, M YAMADA, Y KLEINMAN, HK AF KIM, WH SCHNAPER, HW NOMIZU, M YAMADA, Y KLEINMAN, HK TI APOPTOSIS IN HUMAN FIBROSARCOMA CELLS IS INDUCED BY A MULTIMERIC SYNTHETIC TYR-ILE-GLY-SER-ARG (YIGSR)-CONTAINING POLYPEPTIDE FROM LAMININ SO CANCER RESEARCH LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; EXPERIMENTAL METASTASIS FORMATION; BASEMENT-MEMBRANE; TUMOR-GROWTH; TISSUE TRANSGLUTAMINASE; EXTRACELLULAR-MATRIX; LUNG METASTASIS; PEPTIDE; DEATH; INHIBITION AB The YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide, derived from the laminin beta(1) chain, decreases tumor metastasis and growth in experimental animals. The mechanism responsible fdr this inhibition is not known. We now report that a 16-mer branched form of YIGSR, synthesized by the multimeric antigen peptide system, induced the apoptosis of HT-1080 cells in vitro at 30 mu g/ml (approximately 3 mu M). Tumor cells treated with this peptide showed the expected morphological changes associated with apoptosis, acridine orange staining of nuclei, increased numbers of 3'-OH ends of DNA in nuclei, a DNA ladder pattern on agarose gels, and increased transforming growth factor beta(1) mRNA by Northern blot. The specificity of this peptide was confirmed by inhibition of apoptosis with a neutralizing antibody to the peptide. In addition, the branched 16-mer peptides of scrambled sequence did not induce apoptosis. Our in vitro results suggest that apoptosis may play a role in the antimetastatic and antitumor effects associated with the YIGSR peptide. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. SEOUL NATL UNIV,COLL MED,DEPT PATHOL,SEOUL 110799,SOUTH KOREA. RI Kim, Wooho/G-3703-2011; Seoul National University, Pathology/B-6702-2012 NR 45 TC 57 Z9 57 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 SEP 15 PY 1994 VL 54 IS 18 BP 5005 EP 5010 PG 6 WC Oncology SC Oncology GA PF791 UT WOS:A1994PF79100027 PM 8069868 ER PT J AU THORGEIRSSON, SS AF THORGEIRSSON, SS TI ALTERATIONS OF TUMOR-SUPPRESSOR GENES AND ALLELIC LOSSES IN HUMAN HEPATOCELLULAR CARCINOMAS IN CHINA - REPLY SO CANCER RESEARCH LA English DT Letter RP THORGEIRSSON, SS (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 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 SEP 15 PY 1994 VL 54 IS 18 BP 5022 EP 5023 PG 2 WC Oncology SC Oncology GA PF791 UT WOS:A1994PF79100032 ER PT J AU NICHOLSON, JKA RAO, PE CALVELLI, T STETLERSTEVENSON, M BROWNING, SW YEUNG, L MARTI, GE AF NICHOLSON, JKA RAO, PE CALVELLI, T STETLERSTEVENSON, M BROWNING, SW YEUNG, L MARTI, GE TI ARTIFACTUAL SHINING OF MONOCLONAL-ANTIBODIES IN 2-COLOR COMBINATIONS IS DUE TO AN IMMUNOGLOBULIN IN THE SERUM AND PLASMA SO CYTOMETRY LA English DT Article DE FLOW CYTOMETRY; IMMUNOPHENOTYPING; MONOCLONAL ANTIBODIES; FLUORESCEIN; PHYCOERYTHRIN AB Two-color whole blood lysis is the assay of choice for lymphocyte immunophenotyping because of the additional information it provides. Recently, artifactual double-staining of some specimens has been observed with this assay. In these cases, the samples appear to be uncompensated for spectral overlap or to inappropriately coexpress two antigens simultaneously. This artifact can result in the apparent coexpression of CD4 and CD8 (observed in lymphoblastic processes) or of CD5 and CD20 (characteristic of chronic lymphocytic leukemia) in normal persons, leading to an erroneous diagnosis. Using plasma, serum, or immunoglobulin preparations from donors who exhibit this artifact we sought to determine 1) the source of the artifact and 2) ways to overcome it. This staining is apparently due to an immunoglobulin in the donors' serum and plasma which does not have specific reactivity with mouse immunoglobulin. Washing whole blood samples or blocking with mouse immunoglobulin is a convenient way of avoiding this artifact. (C) 1994 Wiley-Liss, Inc. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,ATLANTA,GA 30341. ORTHODIAGNOST SYST INC,ORTHOMUNE RES,RARITAN,NJ. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. NCI,DEPT PATHOL,BETHESDA,MD 20892. FED DRUG ADM,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPIES,MED & MOLEC GENET LAB,BETHESDA,MD. NR 6 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD SEP 15 PY 1994 VL 18 IS 3 BP 140 EP 146 DI 10.1002/cyto.990180305 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PE248 UT WOS:A1994PE24800004 PM 7529155 ER PT J AU NUNESDUBY, SE TIRUMALAI, RS DORGAI, L YAGIL, E WEISBERG, RA LANDY, A AF NUNESDUBY, SE TIRUMALAI, RS DORGAI, L YAGIL, E WEISBERG, RA LANDY, A TI LAMBDA INTEGRASE CLEAVES DNA IN CIS SO EMBO JOURNAL LA English DT Article DE DNA CLEAVAGE; HK022 INTEGRASE; HOLLIDAY JUNCTIONS; LAMBDA INTEGRASE; SITE-SPECIFIC RECOMBINATION ID SITE-SPECIFIC RECOMBINATION; STEP-ARREST MUTANTS; FLP RECOMBINASE; ACTIVE-SITE; BACTERIOPHAGE-LAMBDA; SACCHAROMYCES-CEREVISIAE; HOLLIDAY STRUCTURES; TOPOISOMERASE-I; STRAND TRANSFER; GENE-PRODUCT AB In the Int family of site-specific recombinases, DNA cleavage is accomplished by nucleophilic attack on the activated scissile phosphodiester bond by a specific tyrosine residue, It has been proposed that this tyrosine is contributed by a protomer bound to a site other than the one being cleaved ('trans' cleavage). To test this hypothesis, the difference in DNA binding specificity between closely related integrases (Ints) from phages lambda and HK022 was exploited to direct wild type Ints and cleavage- or activation-defective mutants to particular sites on bispecific substrates. Analysis of Int cleavage at individual sites strongly indicates that DNA cleavage is catalyzed by the Int bound to the cleaved site ('cis' cleavage). This conclusion contrasts with those from previous experiments with two members of the Int family, FLP and lambda Int, that supported the hypothesis of trans cleavage. We suggest explanations for this difference and discuss the implications of the surprising finding that Int-family recombinases appear capable of both cis and trans mechanisms of DNA cleavage. C1 BROWN UNIV,DIV BIOL & MED,PROVIDENCE,RI 02912. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,IL-69978 TEL AVIV,ISRAEL. FU NIAID NIH HHS [AI 13544]; NIGMS NIH HHS [GM 33928] NR 48 TC 57 Z9 57 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 SEP 15 PY 1994 VL 13 IS 18 BP 4421 EP 4430 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PJ303 UT WOS:A1994PJ30300024 PM 7925285 ER PT J AU SHPAKOVSKI, GV AF SHPAKOVSKI, GV TI THE FISSION YEAST SCHIZOSACCHAROMYCES-POMBE RPB6 GENE ENCODES THE COMMON PHOSPHORYLATED SUBUNIT OF RNA-POLYMERASE AND COMPLEMENTS A MUTATION IN THE CORRESPONDING GENE OF SACCHAROMYCES-CEREVISIAE SO GENE LA English DT Article DE GENE CLONING; NUCLEOTIDE SEQUENCING; RPB6 HOMOLOG; INTRON; INTERGENERIC COMPLEMENTATION; DISTANTLY RELATED YEASTS ID SEQUENCE DETERMINATION; DNA; CLONING; FEATURES AB A single-copy gene, homologous to the RPB6 gene from Saccharomyces cerevisiae, encoding a small phosphorylated subunit common to all three forms of nuclear DNA-dependent RNA polymerase was isolated from the fission yeast Schizosaccharomyces pombe. Its cDNA copy consists of an open reading frame of 142 codons and encodes an acidic protein (predicted pI 4.1) with a M(r), of 15 730. The genomic copy of Sz, pombe rpb6 contains an intron (219 nucleotides) located at codon 92, a position which does not correspond to the single intron of the S. cerevisiae gene. The sequencing of both genomic and cDNA copies of rpb6 allowed us to determine the probable positions of the start and stop of rpb6 transcription and to identify a putative TATA box. The primary structures of the St. pombe and S. cerevisiae Rpb6 proteins have 60.7% identity, with the same general organization: a highly acidic N-terminal region followed by a short basic region and a C terminus featuring a putative heptad Leu repeat. The C-terminal half of the sequence is particularly well conserved and, therefore, probably contains the most important functional domain. Moreover, a heterospecific complementation test showed that rpb6 from Sz. pombe fully complements a complete deletion of its S. cerevisiae homologue. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NIMH,GENOM UNIT,BETHESDA,MD 20892. BYELARUSSIAN ACAD SCI,INST BIOORGAN CHEM,MINSK 220141,BYELARUS. FU NCIPC CDC HHS [CEEI-93] NR 26 TC 33 Z9 34 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 SEP 15 PY 1994 VL 147 IS 1 BP 63 EP 69 DI 10.1016/0378-1119(94)90039-6 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PH564 UT WOS:A1994PH56400008 PM 8088549 ER PT J AU HEINZMANN, C KOJIS, TL GONZALEZ, P RAO, PV ZIGLER, JS POLYMEROPOULOS, MH KLISAK, I SPARKES, RS MOHANDAS, T BATEMAN, JB AF HEINZMANN, C KOJIS, TL GONZALEZ, P RAO, PV ZIGLER, JS POLYMEROPOULOS, MH KLISAK, I SPARKES, RS MOHANDAS, T BATEMAN, JB TI ASSIGNMENT OF THE ZETA-CRYSTALLIN GENE (CRYZ) TO HUMAN-CHROMOSOME 1P22-P-31 AND IDENTIFICATION OF RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISMS SO GENOMICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; HEREDITARY CATARACT; LENS; HAPTOGLOBIN; PROTEIN; LINKAGE; FAMILY AB zeta-Crystallin is a lens protein that has been associated with autosomal dominant congenital cataracts in guinea pigs and thus is a candidate for human congenital cataracts. We have assigned the zeta-crystallin gene (CRYZ) to human chromosome 1 using a Southern panel of 17 human-mouse somatic cell hybrids and regionally localized it to 1p22-p31 by fluorescence in situ hybridization. Five restriction fragment length polymorphisms were identified by analyzing the DNA from 10 unrelated, unaffected individuals. Our results will permit evaluation of its role in human cataractogenesis. (C) 1994 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,CTR HLTH SCI,SCH MED,JULES STEIN EYE INST,CTR VIS GENET,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NEI,BETHESDA,MD 20892. NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DIV MED GENET,TORRANCE,CA 90509. FU NEI NIH HHS [EY00331, EY08282] NR 22 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 15 PY 1994 VL 23 IS 2 BP 403 EP 407 DI 10.1006/geno.1994.1516 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PK060 UT WOS:A1994PK06000011 PM 7835889 ER PT J AU ROTHNAGEL, JA LONGLEY, MA BUNDMAN, DS NAYLOR, SL LALLEY, PA JENKINS, NA GILBERT, DJ COPELAND, NG ROOP, DR AF ROTHNAGEL, JA LONGLEY, MA BUNDMAN, DS NAYLOR, SL LALLEY, PA JENKINS, NA GILBERT, DJ COPELAND, NG ROOP, DR TI CHARACTERIZATION OF THE MOUSE LORICRIN GENE - LINKAGE WITH PROFILAGGRIN AND THE FLAKY TAIL AND SOFT COAT MUTANT LOCI ON CHROMOSOME-3 SO GENOMICS LA English DT Article ID CROSS-LINKED ENVELOPE; EPIDERMAL DIFFERENTIATION; STRATUM-CORNEUM; INTERMEDIATE FILAMENTS; CORNIFIED ENVELOPE; TRICHOHYALIN GENE; BINDING PROTEINS; KERATINOCYTE; PRECURSOR; FILAGGRIN AB Loricrin is the major component of a specialized structure, teamed the cornified cell envelope, that is formed beneath the plasma membrane of stratified squamous epithelial cells and is coexpressed with profilaggrin in terminally differentiating epidermal keratinocytes. Full-length cDNAs for both mouse and human loricrin have been cloned and characterized, as has the human gene. Here we report the isolation and characterization of the mouse loricrin gene. The gene has a simple structure consisting of a single intron of 1091 bp within the 5' noncoding sequence and an uninterrupted open reading frame. Using PCR analyses of DNAs isolated from mouse x Chinese hamster somatic cell hybrids, we have mapped both the loricrin and the profilaggrin genes to chromosome 3. Genetic linkage analysis has shown that mouse loricrin and profilaggrin lie within 1.5 +/- 1.1 centimorgans of each other. We have further shown that both genes map in the vicinity of the flaky tail (ft) and soft coat (soc) loci. These mouse mutants exhibit a number of changes in their integument, suggesting that abnormalities in these genes may contribute to the mutant phenotype. (C) 1994 Academic Press, Inc. C1 BAYLOR COLL MED,DEPT CELL BIOL & DERMATOL,HOUSTON,TX 77030. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78274. ROCHESTER INST TECHNOL,CTR BACCALAUREATE & GRAD STUDIES,ROCHESTER,NY 14623. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Rothnagel, Joe/A-4874-2010 OI Rothnagel, Joe/0000-0002-6710-3165 FU NCI NIH HHS [N01-CO-74101]; NHGRI NIH HHS [HG00470]; NIAMS NIH HHS [AR40240] NR 39 TC 41 Z9 41 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 15 PY 1994 VL 23 IS 2 BP 450 EP 456 DI 10.1006/geno.1994.1522 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PK060 UT WOS:A1994PK06000017 PM 7835895 ER PT J AU KOZAK, CA ADAMSON, MC HOROWITZ, M AF KOZAK, CA ADAMSON, MC HOROWITZ, M TI GENETIC-MAPPING OF THE MOUSE PROSAPOSIN GENE (PSAP) TO MOUSE CHROMOSOME-10 SO GENOMICS LA English DT Note ID SPHINGOLIPID ACTIVATOR PROTEIN-2; CO-BETA-GLUCOSIDASE; SULFATIDE ACTIVATOR; MOLECULAR-CLONING; SAPOSIN; PRECURSOR; DEGRADATION; ASSIGNMENT; EXPRESSION; CDNA C1 NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,DEPT CELL RES & IMMUNOL,IL-69978 RAMAT AVIV,ISRAEL. NR 31 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 15 PY 1994 VL 23 IS 2 BP 508 EP 510 DI 10.1006/geno.1994.1534 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PK060 UT WOS:A1994PK06000029 PM 7835907 ER PT J AU KARLHOFER, FM HUNZIKER, R REICHLIN, A MARGULIES, DH YOKOYAMA, WM AF KARLHOFER, FM HUNZIKER, R REICHLIN, A MARGULIES, DH YOKOYAMA, WM TI HOST MHC CLASS-I MOLECULES MODULATE IN-VIVO EXPRESSION OF A NK CELL-RECEPTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; MARROW GRAFT-REJECTION; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; BONE-MARROW; T-CELLS; HEMATOPOIETIC-CELLS; ANTIGEN RECOGNITION; NK1.1 ANTIGEN AB Target cell expression of certain MHC class I molecules correlates with resistance to lysis by NK cells. To explain this correlation, one hypothesis states that NK cells may possess two types of receptors; one may activate NK cells whereas another, specific for target cell MHC class I molecules, may inhibit natural killing by transducing negative signals. The cell surface molecule, Ly-49, is expressed on an NK cell subpopulation (15% to 20%) in spleens from C57BL/6 (H-2(b)) mice. Previously, we showed that lysis by Ly-49(+) Il-2-activated NK cells was globally inhibited when targets expressed either H-2D(d) or an H-2(kappa)-class I molecule, consistent with the hypothesis that Ly-49 is an inhibitory NK cell receptor that engages these MHC class I molecules. We now have determined the influence of specific host MHC class I molecules on Ly-49 expression. In two-color flow cytometric examination of splenic cells, Ly-49(+)NK1.1(+) cells were undetectable in MHC-congenic strains expressing Dd or D-kappa, in C57BL/6 mice transgenic for membrane-bound Dd, and in B1O.D2(dm1) mice. These data establish that Dd itself is sufficient for this effect and suggest that Ly-49 engages D-d-alpha l/alpha 2 domains. Cross-linking of Ly-49 with membrane-bound Dd may be required because Ly-49(+)NK1.1(+) cells were readily detectable in C57BL/6 strains transgenic for soluble forms of Dd. To examine whether this effect could be the result of down-regulation of Ly-49 expression or negative selection of Ly-49(+) cells, we determined Ly-49 expression on highly purified, freshly isolated NK cell populations (>90% NK1.1(+) CD3(-) cells). These experiments demonstrated that Ly-49(+) cells were present in normal numbers but that Ly-49 expression was markedly decreased in congenic mice expressing H-2D(d) or D-kappa, and in the strain transgenic for membrane-bound H-2D(d). Thus, expression of a putative MHC class I-specific NK cell receptor is modulated by its apparent interaction with alpha 1/alpha 2 domains of host MHC class I molecules. C1 MT SINAI MED CTR,DEPT MED,NEW YORK,NY 10029. UNIV CALIF SAN FRANCISCO,DEPT MED,ROSALIND RUSSELL ARTHRIT RES LAB,SAN FRANCISCO,CA 94110. SAN FRANCISCO GEN HOSP,MED SERV,SAN FRANCISCO,CA 94110. MT SINAI MED CTR,DEPT MICROBIOL,NEW YORK,NY 10029. MT SINAI MED CTR,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029. MT SINAI MED CTR,DEPT PEDIAT,NEW YORK,NY 10029. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 59 TC 119 Z9 119 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 SEP 15 PY 1994 VL 153 IS 6 BP 2407 EP 2416 PG 10 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900005 PM 8077656 ER EF