FN Thomson Reuters Web of Science™ VR 1.0 PT J AU CHIN, KV CHAUHAN, SS ABRAHAM, I SAMPSON, KE KROLCZYK, AJ WONG, M SCHIMMER, B PASTAN, I GOTTESMAN, MM AF CHIN, KV CHAUHAN, SS ABRAHAM, I SAMPSON, KE KROLCZYK, AJ WONG, M SCHIMMER, B PASTAN, I GOTTESMAN, MM TI REDUCED MESSENGER-RNA LEVELS FOR THE MULTIDRUG-RESISTANCE GENES IN CAMP-DEPENDENT PROTEIN-KINASE MUTANT-CELL LINES SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CYCLIC-AMP; P-GLYCOPROTEIN; SOMATOSTATIN GENE; MAMMALIAN-CELLS; MULTIPLE-DRUGS; SUBUNIT GENE; TUMOR-CELLS; MDR GENES; EXPRESSION; TISSUES AB We have previously shown that in Chinese hamster ovary (CHO) cells, a mutant cell line with a defective regulatory subunit (RI) for the cAMP-dependent protein kinase (Abraham et al: Mol. Cell. Biol., 7:3098-3106, 1987), and a transfectant cell line expressing the same mutant kinase, showed increased sensitivity to a number of drugs that are known to be substrates for the multidrug transporter (P-glycoprotein). In the current study we have investigated the mechanism by which cAMP-dependent protein kinase controls drug resistance. We report here that the sensitivity of the kinase defective CHO cell lines to multiple drugs results from decreased RNA levels for the multidrug-resistance gene. Similar results were obtained with mouse Y1 adrenal cells. Wild-type Y1 cells had high levels of P-glycoprotein due to expression of both the mdr1b and mdr2 genes, whereas the cAMP-dependent protein kinase mutant Kin 8 cells had decreased RNA levels for these genes. A Kin 8 transfectant with restored cAMP-dependent protein kinase activity recovered mdr expression, indicating a cause and effect relationship between the protein kinase mutations and mdr expression. No changes in nuclear run-off assays could be detected, suggesting a non-transcriptional mechanism of regulation. Wild-type Y1 cells are more drug sensitive despite having higher levels of P-glycoprotein than the mutant cells. This paradoxical result may be explained by the higher rate of synthesis of steroids by the wild-type Y1 cells, which appear to be inhibitors of P-glycoprotein transport activity. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UPJOHN CO,DEPT CELL BIOL,KALAMAZOO,MI 49001. UNIV TORONTO,DEPT PHARMACOL,TORONTO M5G 1L6,ONTARIO,CANADA. UNIV TORONTO,BANTING & BEST DEPT MED RES,TORONTO M5G 1L6,ONTARIO,CANADA. RI Chin, Khew-Voon/F-2670-2013 NR 53 TC 37 Z9 37 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1992 VL 152 IS 1 BP 87 EP 94 DI 10.1002/jcp.1041520112 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JC609 UT WOS:A1992JC60900011 PM 1352302 ER PT J AU LENANE, MC SWEDO, SE RAPOPORT, JL LEONARD, H SCEERY, W GUROFF, JJ AF LENANE, MC SWEDO, SE RAPOPORT, JL LEONARD, H SCEERY, W GUROFF, JJ TI RATES OF OBSESSIVE-COMPULSIVE DISORDER IN 1ST DEGREE RELATIVES OF PATIENTS WITH TRICHOTILLOMANIA - A RESEARCH NOTE SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE GENETICS; FAMILIAL; TRICHOTILLOMANIA (TTM); OBSESSIVE COMPULSIVE DISORDER (OCD) ID PSYCHIATRIC-DISORDERS; CHILDREN; ADOLESCENTS; CLOMIPRAMINE; DESIPRAMINE; INTERVIEW; AGREEMENT; PARENT AB To explore a possible relationship between trichotillomania, (TTM) (compulsive hair pulling) and Obsessive Compulsive Disorder (OCD), 65 out of 69 (94%) first degree relatives of 16 female probands with severe chronic TTM were compared with two control groups for OCD and for TTM. Three (19%) of the 16 TTM probands had at least one first degree relative with a lifetime history of OCD, and there was an age corrected rate of 6.4% of first degree relatives with OCD. No relative in control group (A) met criteria for OCD. There was a trend (Fishers exact p = .07, two tailed) for a higher rate (age corrected) of OCD in TTM families; these pilot data are consistent with the concept of a spectrum of obsessive compulsive disorders which includes TTM and other pathological grooming behaviours. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP LENANE, MC (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N-240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 86 Z9 87 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD JUL PY 1992 VL 33 IS 5 BP 925 EP 933 DI 10.1111/j.1469-7610.1992.tb01966.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA JD687 UT WOS:A1992JD68700009 PM 1634595 ER PT J AU MILLER, R LAGRONE, J SKOLNICK, P BOJE, KM AF MILLER, R LAGRONE, J SKOLNICK, P BOJE, KM TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR 1-AMINOCYCLOPROPANECARBOXYLIC ACID FROM PLASMA AND BRAIN SO JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS LA English DT Article ID NMDA RECEPTOR COMPLEX; 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID; FUNCTIONAL ANTAGONISTS; EXHIBIT ANTIDEPRESSANT; GLYCINE; PHARMACOKINETICS; CONVULSIONS; ETHYLENE; DILUTION; LIGAND AB A reversed-phase high-performance liquid chromatographic method for the analysis of 1-aminocyclopropanecarboxylic acid (ACPC) from plasma or brain tissue is described. Samples were deproteinized with perchloric acid, centrifuged, alkalinized with potassium hydroxide and recentrifuged. The supernatants were derivatized with o-phthaldialdehyde and injected onto a C18 3-mu-m column (100 mm x 4 mm I.D.) pumped with 1 ml/min methanol-acetonitrile-0.1 M sodium phosphate buffer pH 6.0 (28:5:67, v/v). The retention times for ACPC and the internal standard were 15 and 31 min, respectively. The minimum detectable amount of ACPC was 0.08 nmol. The extraction recovery of ACPC (2.7-270 nmol) from spiked plasma or brain tissue ranged from 88 to 109%. The intra- and inter-day coefficients of variation for 27 nmol ACPC were 3.9 and 4.9%, respectively. This method was utilized to obtain preliminary pharmacokinetic parameters following ACPC administration to mice. C1 NIDDK,NEUROSCI LAB,BLD 8,RM 111,BETHESDA,MD 20892. NR 22 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR-BIOMED JI J. Chromatogr.-Biomed. Appl. PD JUL 1 PY 1992 VL 578 IS 1 BP 103 EP 108 DI 10.1016/0378-4347(92)80230-N PG 6 WC Chemistry, Analytical SC Chemistry GA JF122 UT WOS:A1992JF12200013 PM 1400774 ER PT J AU HAXBY, JV RAFFAELE, K GILLETTE, J SCHAPIRO, MB RAPOPORT, SI AF HAXBY, JV RAFFAELE, K GILLETTE, J SCHAPIRO, MB RAPOPORT, SI TI INDIVIDUAL TRAJECTORIES OF COGNITIVE DECLINE IN PATIENTS WITH DEMENTIA OF THE ALZHEIMER TYPE SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID CEREBRAL METABOLIC ASYMMETRIES; POSITRON EMISSION TOMOGRAPHY; DISEASE; PROGRESSION; PATTERNS AB The course of decline was studied in 16 patients with probable or definite dementia of the Alzheimer type (DAT) over 2.7 to 6.8 years from first to last evaluation. Overall severity of dementia was measured with the Wechsler Adult Intelligence Scale (WAIS), the Dementia Rating Scale (DRS), and the Mini-Mental State Examination (MMSE), at approximately annual intervals. An initial plateau phase, during which language and cognitive functions did not change for periods of 9 to 35 months, was observed in 5 patients who initially had an isolated memory impairment without significant impairment of nonmemory language or visuospatial function. Once nonmemory functions began to decline, the rate of decline was remarkably steady in most individual patients but varied markedly among patients. The initial rate of decline after the plateau phase, as measured with the WAIS and DRS, was a significant predictor of subsequent rate in individual patients (r = .66, p < .01, and r = .67, p < .01, for the WAIS and DRS, respectively). The MMSE was a less reliable measure of longitudinal change in dementia severity and did not predict future rates of decline (r = .29). These results demonstrate a biphasic trajectory of decline in patients with DAT. Stable interindividual differences in rate of decline may provide a basis for designing more sensitive studies of treatments intended to slow or halt the progress of DAT. RP HAXBY, JV (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 97 Z9 97 U1 5 U2 5 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD JUL PY 1992 VL 14 IS 4 BP 575 EP 592 DI 10.1080/01688639208402846 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA JK552 UT WOS:A1992JK55200011 PM 1400920 ER PT J AU SKARULIS, MC WEHMANN, RE NISULA, BC BLITHE, DL AF SKARULIS, MC WEHMANN, RE NISULA, BC BLITHE, DL TI GLYCOSYLATION CHANGES IN HUMAN CHORIONIC-GONADOTROPIN AND FREE ALPHA-SUBUNIT AS GESTATION PROGRESSES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID N-LINKED OLIGOSACCHARIDES; SUGAR CHAINS; CHROMATOGRAPHY; MOLECULES; PREGNANCY; LECTIN; HCG AB Carbohydrate is important to the structure, function, and circulatory survival of the glycoprotein hormones. Human CG (hCG) and the related free-alpha-molecule of pregnancy contain four and two asparagine-linked oligosaccharides, respectively. The present study analyzes changes in the glycosylation patterns of hCG and free-alpha in early vs. late gestation. Five volunteers provided 24-h urine samples, weekly, throughout their pregnancies. Extracts of early pregnancy (weeks 7-12) and late pregnancy (weeks 28-32) urines were pooled. Early and late samples from each patient were subjected to gel filtration to separate hCG and free-alpha, and the populations thus obtained were analyzed by lectin affinity chromatography on Concanavalin A-Sepharose (Con A) and Lens culinaris-agarose (Lch). Using Con A, free-alpha and hCG were separated into an unbound fraction (eluted with Con A buffer), a weakly bound fraction (eluted with 10 mmol alpha-methyl-D-glucoside) and a tightly bound fraction (eluted with 500 mmol alpha-methyl-D-mannoside). For free-alpha-molecule, a significant decrease in tightly bound Con A forms, was noted from early to late pregnancy with a mean difference of 17.0 +/- 2.4% (P < 0.01). Concomitantly, in late pregnancy, an increase in Con A unbound forms of free-alpha was noted with mean difference of 12.5 +/- 1.7% (P < 0.01). These changes indicate the presence of more highly branched oligosaccharides on free-alpha as gestation advances. No changes were noted in the Con A binding of intact hCG; nearly all hCG bound in both early and late pregnancy. Using Lch, free-alpha and hCG were separated into an unbound fraction (eluted with Lch buffer) and a bound fraction (eluted with 500 mmol alpha-methyl-D-mannose). Both free-alpha and intact hCG in late pregnancy exhibited increased binding to Lch, with mean differences from early to late pregnancy of 30.2 +/- 4.8% (P < 0.01) and 11.4 +/- 4.5% (P < 0.05), respectively. These data indicate increased incorporation of fucose into the carbohydrate moieties in late pregnancy. Taken together, these data derived by analysis using lectin specificity imply the presence of more highly branched, fucosylated oligosaccharides as gestation progresses. C1 NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10 N-262, BETHESDA, MD 20892 USA. VET ADM MED CTR, MED SERV, BROOKLYN, NY 11209 USA. NR 27 TC 40 Z9 41 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1992 VL 75 IS 1 BP 91 EP 96 DI 10.1210/jc.75.1.91 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JC175 UT WOS:A1992JC17500017 PM 1377707 ER PT J AU NYOMBA, BL OSSOWSKI, VM SAAD, MF BOGARDUS, C MOTT, DM AF NYOMBA, BL OSSOWSKI, VM SAAD, MF BOGARDUS, C MOTT, DM TI TYROSINE KINASE-ACTIVITY OF SKELETAL-MUSCLE DURING INSULIN INFUSION IN HUMANS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH FACTOR-I; RECEPTOR KINASE; RAT ADIPOCYTES; PROTEIN-KINASE; INVIVO; ACTIVATION; INVITRO; PHOSPHORYLATION; RESISTANCE; MECHANISM AB Insulin receptor tyrosine kinase is stimulated by insulin in vivo, and this provides a mechanism by which the signal from insulin is transmitted into target cells. This study examined the time course of the in vivo activation of the kinase. Five nondiabetic Pima Indians had a euglycemic clamp at an insulin dose of 600 mU/min . m2, resulting in plasma insulin concentrations of about 15 nm by 30 min. Percutaneous muscle biopsies were taken from the vastus lateralis before and at regular intervals during insulin infusion, and the in vivo and in vitro tyrosine kinase activities were measured. There was a rapid in vivo activation of the kinase, detectable at less than 10 min and reaching a maximum within 30 min of insulin infusion. The time course of in vivo kinase activity, plasma insulin concentrations, and insulin-mediated glucose disposal rates displayed parallel patterns, indicating close interrelationships among these variables. The insulin concentration at which the kinase activity was maximal was about 10 nm both in vivo and in vitro. In vitro, however, this maximum increased with the degree of the kinase activation in vivo, indicating that the kinase potential in vitro is dependent on previous insulin exposure in vivo. We conclude that in vivo activation of the insulin receptor tyrosine kinase in human skeletal muscle is a rapid process, related to insulin action on glucose disposal, and that circulating insulin primes inactive insulin receptor molecules for subsequent tyrosine kinase activation by a mechanism that remains to be elucidated. RP NYOMBA, BL (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, 4212 N 16TH ST, ROOM 541, PHOENIX, AZ 85016 USA. NR 34 TC 5 Z9 5 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1992 VL 75 IS 1 BP 218 EP 223 DI 10.1210/jc.75.1.218 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JC175 UT WOS:A1992JC17500039 PM 1619013 ER PT J AU FOLLMANN, D ELLIOTT, P SUH, I CUTLER, J AF FOLLMANN, D ELLIOTT, P SUH, I CUTLER, J TI VARIANCE IMPUTATION FOR OVERVIEWS OF CLINICAL-TRIALS WITH CONTINUOUS RESPONSE SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE CROSSOVER; METAANALYSIS; PARALLEL GROUPS; PRETEST POSTTEST AB Overviews of clinical trials are an efficient and important means of summarizing information about aa particular scientific area. When the outcome is aa continuous variable, both treatment effect and variance estimates are required to construct aa confidence interval for the overall treatment effect. Often, only partial information about the variance is provided in the publication of the clinical trial. This paper provides heuristic suggestions for variance imputation based on partial variance information. Both pretest-posttest (parallel groups) and crossover designs are considered. AA key idea is to use separate sources of incomplete information to help choose aa better variance estimate. The imputation suggestions are illustrated with aa data set. C1 YONSEI UNIV, DEPT PREVENT MED & PUBL HLTH, SEOUL, SOUTH KOREA. UNIV LONDON LONDON SCH HYG & TROP MED, DEPT PUBL HLTH & POLICY, LONDON WC1E 7HT, ENGLAND. RP FOLLMANN, D (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. NR 8 TC 524 Z9 525 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUL PY 1992 VL 45 IS 7 BP 769 EP 773 DI 10.1016/0895-4356(92)90054-Q PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA JC603 UT WOS:A1992JC60300009 PM 1619456 ER PT J AU RITTER, JK YEATMAN, MT FERREIRA, P OWENS, IS AF RITTER, JK YEATMAN, MT FERREIRA, P OWENS, IS TI IDENTIFICATION OF A GENETIC ALTERATION IN THE CODE FOR BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE IN THE UGT1 GENE-COMPLEX OF A CRIGLER-NAJJAR TYPE-I PATIENT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BILIRUBIN; UDP-GLUCURONOSYLTRANSFERASE; HYPERBILIRUBINEMIA; GENETIC DEFECT; DELETION ID URIDINE-DIPHOSPHATE GLUCURONOSYLTRANSFERASE; GUNN-RATS; CLONING; 3-METHYLCHOLANTHRENE; DEFICIENCY; INDUCTION; CELLS; CDNA AB Patients with Crigler-Najjar syndrome (CN) type I inherit an autosomal recessive trait for hyperbilirubinemia, which is characterized by the total absence of bilirubin UDP-glucuronosyltransferase (transferase) activity. The recent identification of two bilirubin transferase isoforms with identical carboxyl termini (Ritter, J. K., J. M. Crawford, and 1. S. Owens. 1991. J. Biol. Chem. 266:1043-1047) led to the discovery of a unique locus, UGT1, which encodes a family of UDP-glucuronosyltransferase isozymes, including the two bilirubin forms (Ritter, J. K., F. Chen, Y. Y. Sheen, H. M. Tran, S. Kimura, M. T. Yeatman, and 1. S. Owens. 1992. J. Biol. Chem. 267:3257-3261). The UGT1 locus features a complex of six overlapping transcriptional units encoding transferases, each of which shares the four most 3' exons (2, 3, 4, and 5) specifying the 3' half of the transferase coding regions (codons 289-533) and the entire 3' untranslated region of each mRNA. This gene model predicts that a single critical mutation in any of these four "common" exons may inactivate the entire family of encoded transferases. In agreement with this prediction, we show here that in the first CN type I individual analyzed (patient F.B.), a 13-bp deletion has occurred in exon 2. Analysis of product generated by the polymerase chain reaction and genomic DNA demonstrated that F.B. is homozygous for the defective allele (UGT1*FB), and that the consanguineous parents are both heterozygotic at this locus. The mutation is predicted to result in the synthesis of severely truncated bilirubin transferase isozymes that are lacking a highly conserved sequence in the carboxyl-terminus and the characteristic membrane (endoplasmic reticulum)-anchoring segment of the protein molecule. C1 NICHHD,HUMAN GENET BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 9S-242,BETHESDA,MD 20892. UNIV ALBERTA,DIV MED GENET,EDMONTON T6G 2E1,ALBERTA,CANADA. NR 32 TC 113 Z9 116 U1 0 U2 1 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 JUL PY 1992 VL 90 IS 1 BP 150 EP 155 DI 10.1172/JCI115829 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JE390 UT WOS:A1992JE39000020 PM 1634606 ER PT J AU SMITH, JW URBA, WJ CURTI, BD ELWOOD, LJ STEIS, RG JANIK, JE SHARFMAN, WH MILLER, LL FENTON, RG CONLON, KC SZNOL, M CREEKMORE, SP WELLS, NF RUSCETTI, FW KELLER, JR HESTDAL, K SHIMIZU, M ROSSIO, J ALVORD, WG OPPENHEIM, JJ LONGO, DL AF SMITH, JW URBA, WJ CURTI, BD ELWOOD, LJ STEIS, RG JANIK, JE SHARFMAN, WH MILLER, LL FENTON, RG CONLON, KC SZNOL, M CREEKMORE, SP WELLS, NF RUSCETTI, FW KELLER, JR HESTDAL, K SHIMIZU, M ROSSIO, J ALVORD, WG OPPENHEIM, JJ LONGO, DL TI THE TOXIC AND HEMATOLOGIC EFFECTS OF INTERLEUKIN-1-ALPHA ADMINISTERED IN A PHASE-I TRIAL TO PATIENTS WITH ADVANCED MALIGNANCIES SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; ACTIVATED KILLER CELLS; CANCER-PATIENTS; RECOMBINANT; INVIVO; MICE; IL-1 C1 FREDERICK MEM HOSP, FREDERICK, MD USA. DAINIPPON PHARMACEUT CO LTD, SUITA, OSAKA 564, JAPAN. BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. PROGRAM RESOURCES INC DYN CORP, FREDERICK, MD USA. DATA MANAGEMENT SERV, FREDERICK, MD USA. FU NCI NIH HHS [N01-CO-74102] NR 39 TC 155 Z9 156 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1992 VL 10 IS 7 BP 1141 EP 1152 PG 12 WC Oncology SC Oncology GA JA771 UT WOS:A1992JA77100017 PM 1607919 ER PT J AU SAROSY, G KOHN, E STONE, DA ROTHENBERG, M JACOB, J ADAMO, DO OGNIBENE, FP CUNNION, RE REED, E AF SAROSY, G KOHN, E STONE, DA ROTHENBERG, M JACOB, J ADAMO, DO OGNIBENE, FP CUNNION, RE REED, E TI PHASE-I STUDY OF TAXOL AND GRANULOCYTE COLONY-STIMULATING FACTOR IN PATIENTS WITH REFRACTORY OVARIAN-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DOSE INTENSITY; TRIAL C1 NCI,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NR 14 TC 195 Z9 196 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1992 VL 10 IS 7 BP 1165 EP 1170 PG 6 WC Oncology SC Oncology GA JA771 UT WOS:A1992JA77100020 PM 1376773 ER PT J AU MUEHRER, P KORETZ, DS AF MUEHRER, P KORETZ, DS TI METHODOLOGICAL LINKAGES FOR PREVENTIVE INTERVENTION RESEARCH - PROCEEDINGS OF A WORKSHOP SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article AB A recent National Institute of Mental Health workshop examined several prominent conceptual models as guides to high-quality preventive intervention research. The conceptual models were compared in terms of four methodological issues, i.e., specifying outcomes to be measured, specifying risk factors or change mechanisms, identifying intervention participants, and designing interventions. This article highlights answers to the methodological linkage questions from the point of view of various models and their implications for preventive intervention research. RP MUEHRER, P (reprint author), NIMH,DIV CLIN RES,PREVENT RES BRANCH,10-85 5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL PSYCHOLOGY PUBL CO PI BRANDON PA 4 CONANT SQUARE, BRANDON, VT 05733 SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JUL PY 1992 VL 20 IS 3 BP 257 EP 267 DI 10.1002/1520-6629(199207)20:3<257::AID-JCOP2290200308>3.0.CO;2-V PG 11 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA JD189 UT WOS:A1992JD18900007 ER PT J AU TANAKA, Y ALBELDA, SM HORGAN, KJ VANSEVENTER, GA SHIMIZU, Y NEWMAN, W HALLAM, J NEWMAN, PJ BUCK, CA SHAW, S AF TANAKA, Y ALBELDA, SM HORGAN, KJ VANSEVENTER, GA SHIMIZU, Y NEWMAN, W HALLAM, J NEWMAN, PJ BUCK, CA SHAW, S TI CD31 EXPRESSED ON DISTINCTIVE T-CELL SUBSETS IS A PREFERENTIAL AMPLIFIER OF BETA-1 INTEGRIN-MEDIATED ADHESION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTES-T; LFA-1; MOLECULE; RECEPTORS; BINDING; ANTIGEN; SURFACE; DIFFERENTIATION; RECOGNITION; ENDOTHELIUM AB The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets, and endothelial cells is postulated to mediate adhesion to endothelial cells and thereby function in immunity, inflammation, and wound healing. We report the following novel features of CD31 which suggest a role for it in adhesion amplification of unique T cell subsets: (a) engagement of CD31 induces the adhesive function of beta-1 and beta-2 integrins; (b) adhesion induction by CD31 immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d) unique subsets of CD4+ and CD8+ T cells express CD31, including all naive (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive function of beta-1 integrins, particularly very late antigen-4, more efficiently than the beta-2 integrin lymphocyte function-associated antigen-1. Conversely, CD3 is more effective in inducing beta-2-mediated adhesion. Taken together, these findings indicate that unique T cell subsets express CD31, and CD31 has the capacity to induce integrin-mediated adhesion of T cells in a sensitive and selective fashion. We propose that, in collaboration with other receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin-mediated adhesion of CD31+ T cells to other cells, particularly endothelial cells. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. WISTAR INST,PHILADELPHIA,PA 19104. BLOOD CTR SE WISCONSIN INC,BLOOD RES INST,MILWAUKEE,WI 53233. UNIV PENN,DEPT MED,PULM & CRIT CARE SECT,PHILADELPHIA,PA 19104. UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. OTSUKA AMER PHARMACEUT INC,DEPT ENDOTHELIAL CELL BIOL,ROCKVILLE,MD 20850. NR 53 TC 349 Z9 350 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1992 VL 176 IS 1 BP 245 EP 253 DI 10.1084/jem.176.1.245 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JA759 UT WOS:A1992JA75900025 PM 1377224 ER PT J AU DEARRY, A AF DEARRY, A TI ELECTRORETINOGRAMS AND CIRCADIAN-RHYTHMS IN GREEN SUNFISH SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Letter ID SPECTRAL SENSITIVITY; RETINA RP DEARRY, A (reprint author), NIH,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 1992 VL 100 IS 1 BP 171 EP 174 DI 10.1085/jgp.100.1.171 PG 4 WC Physiology SC Physiology GA JD493 UT WOS:A1992JD49300010 PM 1512557 ER PT J AU KANAGAWA, O NUSSRALLAH, BA WIEBENGA, ME MURPHY, KM MORSE, HC CARBONE, FR AF KANAGAWA, O NUSSRALLAH, BA WIEBENGA, ME MURPHY, KM MORSE, HC CARBONE, FR TI MURINE AIDS SUPERANTIGEN REACTIVITY OF THE T-CELLS BEARING V-BETA-5 T-CELL ANTIGEN RECEPTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; BETA-CHAIN; MOLECULAR-GENETICS; ALPHA-CHAIN; CLASS-I; EXPRESSION; LYMPHOCYTES; DETERMINANT; IDENTIFICATION; RECOGNITION AB A B cell line, B6-1710, that expresses the defective virus known to induce murine AIDS stimulates a large fraction of nonprimed splenic T cells. Analysis of the T cell population responding to the B6-1710 for TCR V-beta-chain usage revealed that, in addition to the previously reported V-beta-5-chain-positive T cells, T cells bearing V-beta-11 and V-beta-12 are also specifically enriched. We have established V-beta-5+ T cell lines, clones, and hybridomas expressing identical TCR with different CD4/CD8 phenotypes and demonstrated that T cell reactivity to B6-1710 is, although not absolute, dependent on the presence of CD4 molecules. Further analysis of T cell hybridomas with known J-beta-chain usage revealed that D-beta- and J-beta-chain usage do not play crucial roles in T cell reactivity to B6-1710 B cells. However, T cell hybridomas derived from TCR-V-beta gene transgenic mice were found to be heterogeneous for their reactivity to B6-1710, suggesting that the V-alpha-chains associating with the transgenic V-beta-chain determine T cell responsiveness to B6-1710. These data clearly demonstrate that T cell reactivity to a murine AIDS virus expressing B cell line resembles that previously reported for Mls-like superantigens. C1 WASHINGTON UNIV, SCH MED, DEPT MED, ST LOUIS, MO 63110 USA. NIAID, BETHESDA, MD 20892 USA. MONASH UNIV, DEPT PATHOL & IMMUNOL, CLAYTON, VIC 3168, AUSTRALIA. RP KANAGAWA, O (reprint author), WASHINGTON UNIV, SCH MED, DEPT PATHOL, BOX 8118, 660 S EUCLID AVE, ST LOUIS, MO 63110 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [AI 30803] NR 39 TC 52 Z9 52 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 9 EP 16 PG 8 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900002 PM 1351503 ER PT J AU KIM, YH PROUST, JJ BUCHHOLZ, MJ CHREST, FJ NORDIN, AA AF KIM, YH PROUST, JJ BUCHHOLZ, MJ CHREST, FJ NORDIN, AA TI EXPRESSION OF THE MURINE HOMOLOG OF THE CELL-CYCLE CONTROL PROTEIN P34(CDC2) IN LYMPHOCYTES-T SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MATURATION-PROMOTING FACTOR; CONTROL GENE CDC2+; M-PHASE; PHOSPHORYLATION SITES; NUCLEOTIDE-SEQUENCE; NUCLEAR LAMINA; KINASE; INTERLEUKIN-2; ACTIVATION; MITOSIS AB The mammalian homologue of the cdc2 gene of the fission yeast Schizosaccharomyces pombe encodes a p34cdc2 cyclin-dependent kinase that regulates the cell cycle of a wide variety of cell types. Resting murine T lymphocytes contained no detectable p34cdc2 protein, histone kinase activity, or specific mRNA for the cdc2 gene. Activation of the T cells by immobilized anti-CD3 resulted in the expression of specific mRNA late in the G1 phase of the cell cycle, and p34cdc2 protein was detectable at or near G1/S. At this point in the cell cycle, the protein was phosphorylated at tyrosine and displayed no H-1 histone kinase activity. As the cells progressed through the cycle, the amount of specific mRNA and p34cdc2 increased, and H-1 histone kinase activity was detectable when the cells were blocked at G2/M by nocodazole. The activation of T cells by phorbol dibutyrate induced the expression of IL-2R but failed to induce the synthesis of IL-2 or the expression of cdc2-specific mRNA. Under these conditions, the activated cells failed to enter the S phase of the cell cycle. Because the presence of IL-2 added exogenously during activation by phorbol dibutyrate resulted in the expression of cdc2-specific mRNA and progression through the cell cycle, either IL-2 or the interaction with IL-2R may be involved in the expression of cdc2 and regulation of the G1/S transition. C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224. INST UNIV GERIATR GENEVE,IMMUNOBIOL AGING LAB,CH-1226 THONEX,SWITZERLAND. NR 49 TC 54 Z9 54 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 17 EP 23 PG 7 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900003 PM 1637418 ER PT J AU ENK, AH KATZ, SI AF ENK, AH KATZ, SI TI IDENTIFICATION AND INDUCTION OF KERATINOCYTE-DERIVED IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNTHESIS INHIBITORY FACTOR; T-HELPER CELL; LANGERHANS CELLS; TH1 CLONES; EPIDERMAL-CELLS; ACTIVATION; GAMMA; SKIN AB It has previously been demonstrated that the epidermis is a rich source of proinflammatory cytokines and growth factors and that complex interactions between these factors may affect inflammatory responses in skin. To investigate whether IL-10 (cytokine synthesis inhibitory factor) is part of this complex process, RNA was extracted from normal epidermis at various times after application of various chemicals to murine skin and mRNA signals for IL-10 were sought using a quantitative reverse-transcriptase-polymerase chain reaction technique. IL-10 signal strength was normalized to that of beta-actin in each sample. IL-10 mRNA signals were occasionally identified in normal epidermis but were uniformly enhanced 4 h after hapten application, and were maximal after 12 h. Contact allergens induced IL-10 mRNA signals whereas vehicles and irritants did not. Depletion of Langerhans cells, Thy-1+ dendritic epidermal cells, and T lymphocytes demonstrated that keratinocytes were the main source of IL-10 mRNA. IL-10 signals were also detected in mRNA derived from PAM 212 (spontaneously transformed keratinocyte) cells. IL-10 protein could be detected by immunoprecipitation, with an IL-10 mAB, of supernatants obtained 16 h after cultured epidermal cells were coupled with hapten. This study demonstrates that murine keratinocytes are capable of producing IL-10 mRNA and protein, and that signal strength of IL-10 mRNA is enhanced by hapten application. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N 238,BETHESDA,MD 20892. NR 26 TC 310 Z9 313 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 92 EP 95 PG 4 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900014 PM 1607665 ER PT J AU HORGAN, C BROWN, K PINCUS, SH AF HORGAN, C BROWN, K PINCUS, SH TI EFFECT OF H-CHAIN V-REGION ON COMPLEMENT ACTIVATION BY IMMOBILIZED IMMUNE-COMPLEXES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MUTANT MONOCLONAL-ANTIBODIES; INCREASED ANTIGEN-BINDING; CROSS-REACTIVE IDIOTYPE; SURFACE HAPTEN DENSITY; SYNTHETIC POLYPEPTIDES; ALPHA(1->6) DEXTRAN; DNA AUTOANTIBODIES; VARIABLE REGIONS; MOUSE ANTIBODIES AB Activation of C by immune complexes (IC) in tissues and the inflammatory consequences are major determinants in the pathogenesis of many autoimmune disorders. To assess the factors involved in C activation by such IC, we examined the binding of C components by chimeric IgG1 antibodies bound to immobilized Ag. We previously reported that alterations in the H chain V regions can affect the binding of first component of C (Clq) and a major breakdown product of the third C component (C3b) when otherwise identical antibodies were bound to immobilized (Tyr, Glu)-Ala-Lys. To evaluate C activation of these antibodies in well defined IC, we utilized a 9-amino acid peptide conjugated to BSA as Ag. The peptide:BSA conjugate was bound similarly by the two IgG1 antibodies which differed mainly in the CDR3 regions, but also in 9 other amino acids in the H chain V region. When soluble IC were prepared with the two antibodies, they activated C similarly. However, C activation by solid phase Ag:antibody complexes differed; we found that antibody 10B bound more Clq and C3b than antibody B11 did, unless the Ag was present at high density on the plates. These data suggest that the variable region differences affect C activation by these antibody when they are bound to immobilized Ag. Furthermore, these results underscore the differences in C activation by the same antibody depending upon whether the IC are free in solution or immobilized. RP HORGAN, C (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 42 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 127 EP 135 PG 9 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900020 PM 1607649 ER PT J AU GAZZINELLI, R XU, YH HIENY, S CHEEVER, A SHER, A AF GAZZINELLI, R XU, YH HIENY, S CHEEVER, A SHER, A TI SIMULTANEOUS DEPLETION OF CD4+ AND CD8+ LYMPHOCYTES-T IS REQUIRED TO REACTIVATE CHRONIC INFECTION WITH TOXOPLASMA-GONDII SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; IFN-GAMMA; CELLS; ENCEPHALITIS; MICE; RESISTANCE; ANTIBODY; LYT-2+ AB C57BL/6 mice chronically infected with an avirulent strain (ME-49) of Toxoplasma gondii were used to study the mechanisms by which T lymphocytes and IFN-gamma prevent reactivation of latent infection. Infected animals were treated with mAb, either anti-CD8, anti-CD4, anti-CD4 plus anti-CD8, anti-IFN-gamma, or anti-CD4 plus anti-IFN-gamma and the mice followed for survival, histopathology, cyst numbers, and spleen cell cytokine responses. In agreement with previously published findings, treatment with anti-IFN-gamma antibodies fully reactivated the asymptomatic infection, inducing massive necrotic areas in the brain with the appearance of free tachyzoites and death of all animals within 2 wk. Mice treated with the combination of anti-CD4 plus anti-CD8 antibodies showed augmented pathology and mortality nearly identical to the anti-IFN-gamma treated animals. In contrast, treatment with anti-CD4 or anti-CD8 mAb alone failed to result in significantly enhanced brain pathology or mortality. In additional experiments, full reactivation of infection was observed in mice treated with anti-CD4 plus anti-IFN-gamma indicating that CD4+ lymphocytes are not required for the pathology resulting from IFN-gamma neutralization. Cytokine measurements on parasite Ag-stimulated spleen cells from mAb-treated mice indicated that both CD4+ and CD8+ cells produce IFN-gamma whereas only CD4+ cells contribute to parasite Ag-induced IL-2 synthesis. Together, these results suggest that CD4+ and CD8+ lymphocytes act additively or synergistically to prevent reactivation of chronic T. gondii infection probably through the production of IFN-gamma. RP GAZZINELLI, R (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 20 TC 363 Z9 371 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 175 EP 180 PG 6 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900026 PM 1351500 ER PT J AU GOSSELIN, J FLAMAND, L DADDARIO, M HISCOTT, J STEFANESCU, I ABLASHI, DV GALLO, RC MENEZES, J AF GOSSELIN, J FLAMAND, L DADDARIO, M HISCOTT, J STEFANESCU, I ABLASHI, DV GALLO, RC MENEZES, J TI MODULATORY EFFECTS OF EPSTEIN-BARR, HERPES-SIMPLEX, AND HUMAN HERPES-6 VIRAL-INFECTIONS AND COINFECTIONS ON CYTOKINE SYNTHESIS - A COMPARATIVE-STUDY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; T-CELL RECOGNITION; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN B-CELLS; HUMAN HERPESVIRUS-6; EXANTHEM SUBITUM; HUMAN-MONOCYTES; MESSENGER-RNA; LYMPHOCYTES-T; FACTOR-ALPHA AB Herpesviruses such as EBV, HSV, and human herpes virus-6 (HHV-6) have a marked tropism for cells of the immune system and therefore infection by these viruses may result in alterations of immune functions, leading at times to a state of immunosuppression. We report the results of a comparative study in which we found that EBV, HSV-1, and HHV-6 act differentially on the immune system with regard to their effect on the synthesis of IL-1-beta, IL-6, and TNF-alpha, i.e., three immunoregulatory cytokines mainly secreted by activated monocytes/macrophages. Using the polymerase chain reaction technique, analyses of the mRNA levels for each of the three monokines after viral infection indicated that the effect exerted by each of these herpesviruses on cytokine synthesis by human PBMC was detectable at the transcriptional level. Different amounts of IL-1-beta protein were detected in infected PBMC cultures, HHV-6 being the strongest IL-1-beta up-regulator among these three herpesviruses. Spontaneous releases of IL-6 and TNF-alpha were found reduced after infection by HHV-6 and EBV, respectively. In comparison to EBV and HHV-6, HSV-1 proved to be a weak monokine enhancer. Results of coinfection studies indicated that virus-induced suppressive effects on cytokine synthesis are dominant. In fact, EBV inhibited TNF-alpha synthesis even in the presence of HHV-6, a strong up-regulator of TNF-alpha synthesis. Similarly, EBV was unable to stimulate IL-6 production in the presence of HHV-6. Viral structural component(s) appeared to be responsible for the up-regulation of IL-6 by both EBV and HSV-1, and of TNF-alpha by HSV-1. Taken together, our observations illustrate that herpesviruses can selectively regulate cytokine synthesis thereby disturbing immune homeostasis; this effect may favor pathogenic events, including the reactivation and/or spread of other infectious agents within the host. C1 ST JUSTINE HOSP,IMMUNOVIROL LAB,3175 ST CATHERINE RD,MONTREAL H3T 1C5,QUEBEC,CANADA. LADY DAVIS INST MED RES,MONTREAL H3T 1E2,QUEBEC,CANADA. NCI,BETHESDA,MD 20892. UNIV MONTREAL,FAC MED,PEDIAT RES CTR,IMMUNOVIROL LAB,MONTREAL H3C 3J7,QUEBEC,CANADA. NR 63 TC 99 Z9 99 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 JUL 1 PY 1992 VL 149 IS 1 BP 181 EP 187 PG 7 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900027 PM 1318897 ER PT J AU UTZ, U KOENIG, S COLIGAN, JE BIDDISON, WE AF UTZ, U KOENIG, S COLIGAN, JE BIDDISON, WE TI PRESENTATION OF 3 DIFFERENT VIRAL PEPTIDES, HTLV-1 TAX, HCMV GB, AND INFLUENZA-VIRUS M1, IS DETERMINED BY COMMON STRUCTURAL FEATURES OF THE HLA-A2.1 MOLECULE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; SIDE-CHAINS; BINDING; RECOGNITION; EPITOPES; SPECIFICITY; MUTATIONS; FLOOR AB To determine whether similar or dissimilar molecular features of class I molecules are involved in the presentation of structurally distinct peptides, we have investigated the influence of different pockets of the HLA-A2.1 molecule on the presentation of three different viral peptides. HTLV-I Tax peptide 12-19, HCMV gB 619-628, and influenza M1 58-66 are minimal peptides that induce HLA-A2.1-restricted noncross-reactive CTL. A detailed analysis of the stuctural features of HLA-A2.1 that are involved in peptide presentation was undertaken using a panel of 11 HLA-A2 mutants with single amino acid substitutions within pockets present in the peptide binding site. Nine of the 11 mutants affected presentation of each of the three peptides, whereas the other two mutants had negative effects on presentation of only two of these viral peptides. These results indicate that common structural features in HLA-A2 determine the binding of different peptides, and help to provide a plausible explanation for how structurally diverse peptides bind to HLA-A2. C1 MEDIMMUNE INC,GAITHERSBURG,MD 20879. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP UTZ, U (reprint author), NINCDS,NEUROIMMUNOL BRANCH,MOLEC IMMUNOL SECT,BLDG 10,ROOM 5B-16,BETHESDA,MD 20892, USA. NR 37 TC 103 Z9 103 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 214 EP 221 PG 8 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900032 PM 1607654 ER PT J AU VANDERVORT, AL DOERFLER, ME STUETZ, P DANNER, RL AF VANDERVORT, AL DOERFLER, ME STUETZ, P DANNER, RL TI ANTAGONISM OF LIPOPOLYSACCHARIDE-INDUCED PRIMING OF HUMAN NEUTROPHILS BY LIPID-A ANALOGS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; BACTERIAL LIPOPOLYSACCHARIDES; POLYMORPHONUCLEAR LEUKOCYTES; MONOSACCHARIDE PRECURSOR; RESPIRATORY BURST; FREE CALCIUM; ENDOTOXIN; LEUKOTRIENE-B4; RELEASE; SUPEROXIDE AB Lipid X, a monosaccharide precursor of the lipid A component of LPS, has been found to antagonize LPS-induced priming of human neutrophils in a manner consistent with competitive inhibition. In this investigation, the inhibition of neutrophil priming by lipid A analogs was found to be specific for LPS-induced priming. Priming of neutrophils by TNF, IL-8, and C5a were all unaffected by increasing concentrations of 3-aza-lipid X-4-phosphate (compound 3), a monosaccharide LPS-antagonist. Unlike lipid X, the pattern of antagonism exhibited by some monosaccharide LPS-antagonists was noncompetitive-like. The relationship between the chemical structure and inhibition pattern was found to be complex and not simply related to the type of acyl linkage at the C-3 position of the glucosamine backbone. Lipid A analogs were found to antagonize calcium ionophore A23187-stimulated leukotriene B4 (LTB4) production from LPS-primed neutrophils in a pattern of inhibition qualitatively similar to that seen with FMLP-stimulated O2- production. Resting and FMLP-stimulated (peak) cytosolic-free calcium levels did not differ significantly between unprimed and LPS-primed neutrophils, (p = 0.67 and p = 0.97, respectively). Furthermore, antagonism of LPS-mediated priming by 3-aza-lipid X-4-phosphate (compound 3) could not be explained by changes in intracellular calcium flux despite marked inhibition of O2- production (p < 0.0001). Thus, lipid A analogs antagonize only LPS-induced priming and the pattern of inhibition is dependent on the chemical structure. Inhibition of LPS-induced priming by lipid A analogs may involve an early step in the signal transduction pathway common to both O2-and LTB4 generation, but independent of intracellular calcium concentration. C1 SANDOZ GMBH,A-1235 VIENNA,AUSTRIA. RP VANDERVORT, AL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,BETHESDA,MD 20892, USA. NR 47 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1992 VL 149 IS 1 BP 359 EP 366 PG 8 WC Immunology SC Immunology GA HZ479 UT WOS:A1992HZ47900050 PM 1318905 ER PT J AU SCHWARTZENTRUBER, DJ SOLOMON, D ROSENBERG, SA TOPALIAN, SL AF SCHWARTZENTRUBER, DJ SOLOMON, D ROSENBERG, SA TOPALIAN, SL TI CHARACTERIZATION OF LYMPHOCYTES INFILTRATING HUMAN BREAST-CANCER - SPECIFIC IMMUNE REACTIVITY DETECTED BY MEASURING CYTOKINE SECRETION SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE BREAST CANCER; TUMOR-INFILTRATING LYMPHOCYTES; TUMOR NECROSIS FACTOR-ALPHA; GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR; INTERFERON-GAMMA ID PERIPHERAL-BLOOD; CLONAL ANALYSIS; MELANOMA-CELLS; TUMOR; IMMUNOTHERAPY; INTERLEUKIN-2; ANTIGENS; LYSIS AB Primary breast cancers from 19 patients and draining lymph nodes from nine of them (seven containing metastatic tumor) were used in growing tumor-infiltrating lymphocytes (TIL) in culture. TIL were studied for proliferation, phenotype, cytotoxicity, and the ability to secrete cytokines in response to autologous tumor. Lymphocytes from primary breast tumors proliferated in 15 of 19 cultures, a median of 6.7 X 10(3)-fold in 65 days. For eight of nine patients, lymphocytes derived from draining lymph nodes proliferated in culture, a median of 110-fold in 49 days. Breast TIL became predominantly CD4+ cells over time in culture and were 73% CD4+ and 21% CD8+ (means) at 63 days (median). Lymph node lymphocytes were 63% CD4+ at 51 days. TIL were poorly lytic in 4-hour Cr-51 release assays. Lysis of autologous tumor occurred in only one of 12 breast TIL and one of nine lymph node cultures. This lysis was low (15% at effector:target = 40:1) and was nonspecific (non-major-histocompatibility-complex restricted). Cytokine secretion was tested by co-culturing TIL with autologous or allogeneic tumors for 24 hours. Cytokines were measured in culture supernatants by enzyme-linked immunosorbent assay or radioimmunoassay. TIL from three of 11 patients specifically secreted granulocyte macrophage-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma when stimulated by autologous tumor and not by a panel of four to five allogeneic breast cancers. Cytokine secretion has made possible the identification of lymphocytes infiltrating breast cancers with specific immune reactivity. This finding will guide the development of new immunotherapies for patients with breast cancer. C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. RP SCHWARTZENTRUBER, DJ (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B51,BETHESDA,MD 20892, USA. NR 27 TC 81 Z9 82 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1992 VL 12 IS 1 BP 1 EP 12 DI 10.1097/00002371-199207000-00001 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA HZ096 UT WOS:A1992HZ09600001 PM 1637779 ER PT J AU ANDERSON, PM KATSANIS, E SENCER, SF HASZ, D OCHOA, AC BOSTROM, B AF ANDERSON, PM KATSANIS, E SENCER, SF HASZ, D OCHOA, AC BOSTROM, B TI DEPOT CHARACTERISTICS AND BIODISTRIBUTION OF INTERLEUKIN-2 LIPOSOMES - IMPORTANCE OF ROUTE OF ADMINISTRATION SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CYTOKINE; LIPOSOMES; INTERLEUKIN-2; PHARMACOKINETICS ID PURIFIED HUMAN INTERLEUKIN-2; ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; HALF-LIFE; MICE; INVIVO; RATS; IMMUNOTHERAPY; ENHANCEMENT; METASTASES AB Due to rapid clearance of interleukin-2 (IL-2), it has had limited effective use as an in vivo immunostimulant. Current experimental and clinical protocols generally must utilize large doses, multiple injections, or continuous infusions of IL-2 in order to achieve significant immunostimulation, often at the expense of systemic toxicity. Therefore, the pharmacodynamics of IL-2 liposomes were investigated. IL-2 liposome incorporation efficiency was 80.4% (SD 5.5); vesicle diameter was 1.65-mu-m (SD 0.09) as determined by fluorescence-activated cell sorting (FACS). Both formulation (free cytokine vs. IL-2 liposomes) and route of administration were important variables in determination of the biodistribution and pharmacokinetic characteristics of IL-2. When free [I-125]IL-2 was given i.v. to mice, only 6.5% was in the blood and 3% in liver and spleen 2 h after injection; on the other hand, at 2 h > 700% of i.v. [I-125]IL-2 liposomes were detected in the blood, liver, spleen, and lungs. Mean i.v. elimination t 1/2, from the blood of rats given 20 x 10(6) U/kg free cytokine or IL-2 liposomes was 41 versus 102 min, respectively, as measured by bioassay and 59 and 119 min as measured by enzyme immunoassay (EIA). After i.v. administration, the estimated V(d) of IL-2 liposomes was 13-fold smaller than the free cytokine. Intrathoracic (i.tx.), i.p., and s.c. administration of [I-125]IL-2 to mice also demonstrated significant depot effects when IL-2 was incorporated into liposomes. These data suggest IL-2 liposomes may provide in vivo immunostimulation superior to the free cytokine due to biodistribution and depot characteristics. C1 UNIV MINNESOTA,DEPT PEDIAT,DIV HEMATOL ONCOL,MINNEAPOLIS,MN 55455. NCI,FREDERICK CANC CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [IR29-CA53517-01] NR 39 TC 54 Z9 54 U1 2 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1992 VL 12 IS 1 BP 19 EP 31 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA HZ096 UT WOS:A1992HZ09600003 PM 1637781 ER PT J AU MALONEY, EM BIGGAR, RJ NEEL, JV TAYLOR, ME HAHN, BH SHAW, GM BLATTNER, WA AF MALONEY, EM BIGGAR, RJ NEEL, JV TAYLOR, ME HAHN, BH SHAW, GM BLATTNER, WA TI ENDEMIC HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-II INFECTION AMONG ISOLATED BRAZILIAN AMERINDIANS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LEUKEMIA-VIRUS; HTLV-I; HIGH PREVALENCE; DRUG-ABUSERS; TRANSMISSION; ANTIBODY; POPULATIONS; LYMPHOMA; INDIANS; RETROVIRUSES AB Evidence for human T cell lymphotropic viruses (HTLV) was sought in sera and cells collected from adults in 13 isolated South and Central American indian tribes. Serologic tests identified frequent HTLV-II-like reactivity among the Cayapo and Kraho tribes, who live 330 km apart in Central Brazil. Polymerase chain reaction analyses of viral DNA in cell pellet and plasma fractions confirmed the virus as HTLV-II. Both tribes speak Ge and, at the time of blood collection (1974), subsisted as hunter/gatherers and slash and burn agriculturalists. Further testing of plasma from Cayapo and Kraho of all ages revealed overall HTLV-II prevalence rates of 33.3% and 12.2%, respectively, with increasing prevalence associated with age and female gender. These data reveal for the first time a high prevalence of HTLV-II infection in remote South American Indians with little contact with non-Indians. Thus, HTLV-II is postulated to be an ancient human virus in the New World. C1 NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48104. UNIV ALABAMA,DEPT HEMATOL & ONCOL,BIRMINGHAM,AL 35294. FU NCI NIH HHS [CP9-5663, CP7-4102] NR 51 TC 178 Z9 183 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1992 VL 166 IS 1 BP 100 EP 107 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HZ746 UT WOS:A1992HZ74600015 PM 1607683 ER PT J AU WALSH, TJ LEE, JW MELCHER, GP NAVARRO, E BACHER, J CALLENDER, D REED, KD WU, T LOPEZBERESTEIN, G PIZZO, PA AF WALSH, TJ LEE, JW MELCHER, GP NAVARRO, E BACHER, J CALLENDER, D REED, KD WU, T LOPEZBERESTEIN, G PIZZO, PA TI EXPERIMENTAL TRICHOSPORON INFECTION IN PERSISTENTLY GRANULOCYTOPENIC RABBITS - IMPLICATIONS FOR PATHOGENESIS, DIAGNOSIS, AND TREATMENT OF AN EMERGING OPPORTUNISTIC MYCOSIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LATEX AGGLUTINATION-TEST; CANDIDA-ALBICANS; CRYPTOCOCCAL ANTIGEN; BEIGELII INFECTION; PATIENT; KETOCONAZOLE; MICONAZOLE; CUTANEUM; INVITRO; HOST AB Disseminated Trichosporon infection, an uncommon but emerging opportunistic mycosis due to Trichosporon beigelii, is frequently difficult to diagnose, refractory to treatment, and associated with a high attributable mortality. Models of disseminated and gastrointestinal Trichosporon infection were developed in persistently granulocytopenic rabbits. The patterns of infection resembled those of clinical disease, including cutaneous lesions, chorioretinitis, renal infection, pulmonary infection, and antigenemia cross-reactive with cryptococcal capsular polysaccharide. Antigenemia, an early manifestation of disseminated Trichosporon infection, originated in vivo from a fibrillar extracellular matrix. Trichosporon organisms disseminated from the gastrointestinal tract to visceral tissue in colonized immunosuppressed rabbits, whereas there was no dissemination from the gastrointestinal tract of otherwise normal rabbits. The antifungal triazoles, fluconazole and SCH 39304, were most active; maximum tolerated doses of amphotericin B and liposomal amphotericin B were ineffective. Trichosporon antigenemia declined in response to antifungal therapy. These findings contribute to improved understanding of the pathogenesis, diagnosis, and treatment of disseminated Trichosporon infection. C1 NIH,NATL CTR RES RESOURCES,SURG & RADIOL UNIT,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,CLIN MICROBIOL LAB,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,INFECT DIS SERV,LACKLAND AFB,TX 78236. WILFORD HALL USAF MED CTR,DEPT PATHOL,LACKLAND AFB,TX 78236. UNIV TEXAS,MD ANDERSON HOSP & TUMOR INST,DIV MED,IMMUNOL & DRUG CARRIERS SECT,HOUSTON,TX 77030. RP WALSH, TJ (reprint author), NCI,INFECT DIS SECT,PEDIAT BRANCH,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA. NR 36 TC 75 Z9 78 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL PY 1992 VL 166 IS 1 BP 121 EP 133 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HZ746 UT WOS:A1992HZ74600018 PM 1535092 ER PT J AU TANG, A UDEY, MC AF TANG, A UDEY, MC TI EFFECTS OF ULTRAVIOLET-RADIATION ON MURINE EPIDERMAL LANGERHANS CELLS - DOSES OF ULTRAVIOLET-RADIATION THAT MODULATE ICAM-1 (CD54) EXPRESSION AND INHIBIT LANGERHANS CELL-FUNCTION CAUSE DELAYED CYTOTOXICITY INVITRO SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID PROSTAGLANDIN-D SYNTHETASE; COLONY-STIMULATING FACTOR; CONTACT HYPERSENSITIVITY; UV-RADIATION; BONE-MARROW; RAT SKIN; LIGHT; PHOTOIMMUNOLOGY; SUPPRESSION; IRRADIATION AB Low doses (100 J/m2) of ultraviolet B (UVB) radiation from sunlamp fluorescent FS20 tubes inhibit the ability of freshly isolated murine epidermal Langerhans cells (LC) to support anti-CD3 MoAb-induced T-cell mitogenesis and selectively inhibit the upregulation of ICAM-1 expression by LC without causing appreciable cytotoxicity in short-term (less-than-or-equal-to 24 h) incubations (J Immunol 146:3347-3355, 1991). In the present study, epidermal cells (EC) were exposed to UVB radiation or were sham-irradiated and cultured for 24, 48, or 72 h when LC were recovered, enumerated, and assayed for simultaneous expression of I-A antigens and ICAM-1 by flow cytometry. UVB-irradiated LC that had been cultured for 24 h exhibited levels of I-A antigens comparable to those on unirradiated LC but expressed substantially less ICAM-1. After 48 and 72 h, cultured UVB-irradiated LC expressed somewhat lower levels of I-A antigens and markedly less ICAM-1 than unirradiated controls. Although similar numbers of LC were recovered from cultures initiated with UVB-irradiated and unirradiated epidermal cells after 24 h, far fewer identifiable LC were recovered from cultures seeded with irradiated cells at 48 and 72 h (approximately 50 and approximately 10% of control, respectively). The effect of UVB radiation on the survival of LC in vitro was not reversible with exogenous TNF-alpha 125 U/ml) alone or granulocyte/macrophage colony-stimulating factor (5 ng/ml) and IL-1 (50 U/ml) in combination, although these cytokines had modest effects on the expression of I-A antigens and ICAM-1 by cultured UVB-irradiated LC. Results of survival studies performed with enriched LC preparations demonstrated that UVB radiation was clearly cytotoxic for LC and did not merely downregulate surface expression of I-A antigens or alter LC buoyant density. Exposure of LC to radiation from blacklight fluorescent (UVA) tubes (0.25 J/cm2) in the presence of 8-methoxypsoralen (1-mu-g/ml; PUVA) or monochromatic UVC radiation (20 J/m2) also inhibited LC accessory cell function. Results of survival studies performed with EC that had been exposed to PUVA or UVC radiation before culture were similar to those of studies performed with UVB-irradiated cells, although PUVA- and UVC-induced LC cytotoxicity was much more pronounced 48 h after culture initiation than UVB-induced cytotoxicity. UVA radiation alone augmented LC recovery at 24 and 48 h, but did not influence I-A antigen or ICAM-1 expression. The results of these experiments indicate that levels of UV radiation (UVB, UVC, or psoralen + UVA radiation) that inhibit LC accessory cell function and selectively modulate ICAM-1 expression in short-term (less-than-or-equal-to 24 h) cultures are ultimately cytotoxic for LC. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N254,BETHESDA,MD 20892. NR 29 TC 48 Z9 49 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1992 VL 99 IS 1 BP 83 EP 89 PG 7 WC Dermatology SC Dermatology GA JB437 UT WOS:A1992JB43700014 PM 1351507 ER PT J AU MOONEN, CTW SOBERING, G VANZIJL, PCM GILLEN, J VONKIENLIN, M BIZZI, A AF MOONEN, CTW SOBERING, G VANZIJL, PCM GILLEN, J VONKIENLIN, M BIZZI, A TI PROTON SPECTROSCOPIC IMAGING OF HUMAN BRAIN SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; PULSED FIELD GRADIENTS; CHEMICAL-SHIFT; NMR-SPECTROSCOPY; INTRACRANIAL TUMORS; INVIVO; SUPPRESSION; WATER; ECHO; RAT C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,ROCKVILLE,MD 20850. PITTSBURGH NMR INST,PITTSBURGH,PA 15213. NINCDS,NEUROIMAGING SECT,BETHESDA,MD 20892. RP MOONEN, CTW (reprint author), NIH,NCRR,BEIP,INVIVO NMR RES CTR,BLDG 10,ROOM B1D125,BETHESDA,MD 20892, USA. RI van Zijl, Peter/B-8680-2008; Moonen, Chrit/K-4434-2016; OI Moonen, Chrit/0000-0001-5593-3121; von Kienlin, Markus/0000-0002-7972-3003 NR 66 TC 66 Z9 66 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 1992 VL 98 IS 3 BP 556 EP 575 DI 10.1016/0022-2364(92)90007-T PG 20 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JC887 UT WOS:A1992JC88700007 ER PT J AU CECKLER, TL WOLFF, SD YIP, V SIMON, SA BALABAN, RS AF CECKLER, TL WOLFF, SD YIP, V SIMON, SA BALABAN, RS TI DYNAMIC AND CHEMICAL FACTORS AFFECTING WATER PROTON RELAXATION BY MACROMOLECULES SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID MAGNETIC CROSS-RELAXATION; BILAYER-MEMBRANES; CHOLESTEROL; PHOSPHATIDYLCHOLINE; SYSTEM; MODEL C1 JOHNS HOPKINS UNIV,MED CTR,DEPT RADIOL,BALTIMORE,MD 21205. DUKE UNIV,MED CTR,DEPT NEUROBIOL & ANESTHESIOL,DURHAM,NC 27710. RP CECKLER, TL (reprint author), NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. NR 32 TC 72 Z9 73 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD JUL PY 1992 VL 98 IS 3 BP 637 EP 645 DI 10.1016/0022-2364(92)90018-3 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JC887 UT WOS:A1992JC88700018 ER PT J AU KONKEL, ME CORWIN, MD JOENS, LA CIEPLAK, W AF KONKEL, ME CORWIN, MD JOENS, LA CIEPLAK, W TI FACTORS THAT INFLUENCE THE INTERACTION OF CAMPYLOBACTER-JEJUNI WITH CULTURED-MAMMALIAN-CELLS SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; HELA-CELLS; HEP-2 CELLS; ADHESION; ADHERENCE; INFECTION; INVASION; SURFACE; TOXIN AB Although Campylobacter jejuni is now recognised as a common enteric pathogen, the mechanisms by which this organism produces enteritis remain ill-defined. It has been proposed that its abilities to adhere to and enter epithelial cells represent properties essential to virulence. However, the characteristics of these interactions and factors that may influence the association of C. jejuni with epithelial cells are incompletely described. We have determined that the ability of C. jejuni to bind to epithelial cell lines in vitro is significantly affected by the growth temperature and growth stage of the bacteria, but not by growth-medium composition. Binding of C. jejuni to cultured cells is not affected by temperature or phylogenetic origin of the target cell, and exhibits a non-uniform or patchy distribution. In contrast, internalisation is markedly diminished at low temperature, appears to involve active invagination of the target cell membrane via pseudopod formation, and is maximal when cells of human origin are employed. C1 UNIV ARIZONA,DEPT VET SCI,TUCSON,AZ 85721. RP KONKEL, ME (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 22 TC 49 Z9 49 U1 1 U2 3 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JUL PY 1992 VL 37 IS 1 BP 30 EP 37 PG 8 WC Microbiology SC Microbiology GA JC808 UT WOS:A1992JC80800006 PM 1625313 ER PT J AU DAYAN, I HAVLIN, S WEISS, GH AF DAYAN, I HAVLIN, S WEISS, GH TI PHOTON MIGRATION IN A 2-LAYER TURBID MEDIUM - A DIFFUSION ANALYSIS SO JOURNAL OF MODERN OPTICS LA English DT Article ID MODEL; TISSUES; SKIN AB We analyse the diffusion of photons in a two-layer turbid medium, paying specific attention to parameters suggested by the use of lasers for diagnostic purposes in a medical setting. The data produced by such experiments consists of an intensity profile measured on the surface of the medium, which is measured either as a function of time at a fixed distance from the input laser beam, or else as a function of distance keeping the measurement time fixed. In both cases we demonstrate that the presence of a second layer can be detected provided that physical properties of the two layers differ by a sufficient amount, and also show up in calculated values of such parameters as the mean travel time of a photon to the surface of the medium, and the distribution of the maximum depth reached by an arbitrary photon. C1 NIH,BETHESDA,MD 20892. RP DAYAN, I (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. NR 16 TC 44 Z9 44 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0950-0340 J9 J MOD OPTIC JI J. Mod. Opt. PD JUL PY 1992 VL 39 IS 7 BP 1567 EP 1582 DI 10.1080/09500349214551581 PG 16 WC Optics SC Optics GA JH188 UT WOS:A1992JH18800014 ER PT J AU HANSFORD, RG AF HANSFORD, RG TI MITOCHONDRIAL FREE CA2+ IN RELATION TO DEHYDROGENASE ACTIVATION SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract ID FREE CA-2+ CONCENTRATION; PYRUVATE-DEHYDROGENASE; CARDIAC MYOCYTES; TRANSPORT C1 NIA, CARDIOVASC RES LAB, BALTIMORE, MD 21224 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 1992 VL 24 SU 4 BP S32 EP S32 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA JJ556 UT WOS:A1992JJ55600026 ER PT J AU LAKATTA, EG XIAO, RP VENTURA, C GUARNIERI, C SPURGEON, HA CAPOGROSSI, MC GAMBASSI, G AF LAKATTA, EG XIAO, RP VENTURA, C GUARNIERI, C SPURGEON, HA CAPOGROSSI, MC GAMBASSI, G TI NEGATIVE FEEDBACK OF OPIOID PEPTIDE RECEPTOR STIMULATION ON BETA-ADRENERGIC EFFECTS IN HEART-CELLS SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. UNIV SASSARI, INST BIOCHEM, I-07100 SASSARI, ITALY. UNIV BOLOGNA, INST BIOCHEM, I-40126 BOLOGNA, ITALY. NR 6 TC 2 Z9 2 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 1992 VL 24 SU 4 BP S25 EP S25 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA JJ556 UT WOS:A1992JJ55600019 ER PT J AU MASANA, MI BITRAN, JA HSIAO, JK POTTER, WZ AF MASANA, MI BITRAN, JA HSIAO, JK POTTER, WZ TI INVIVO EVIDENCE THAT LITHIUM INACTIVATES-GI MODULATION OF ADENYLATE-CYCLASE IN BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE LITHIUM; CYCLIC AMP; CHOLERA TOXIN; PERTUSSIS TOXIN; FORSKOLIN ID ISLET-ACTIVATING PROTEIN; CYCLIC-AMP ACCUMULATION; PERTUSSIS TOXIN; RAT-BRAIN; CEREBRAL-CORTEX; RECEPTORS; INHIBITION; FORSKOLIN; BINDING; INVITRO AB In vivo microdialysis of cyclic AMP from prefrontal cortex complemented by ex vivo measures was used to investigate the possibility that lithium produces functional changes in G proteins that could account for its effects on adenylate cyclase activity. Four weeks of lithium administration (serum lithium concentration of 0.85 +/- 0.05 mM; n = 11) significantly increased the basal cyclic AMP content in dialysate from prefrontal cortex of anesthetized rats. Forskolin infused through the probe increased dialysate cyclic AMP, but the magnitude of this increase was unaffected by chronic lithium administration. Inactivation of the inhibitory guanine nucleotide binding protein G(i) with pertussis toxin increased dialysate cyclic AMP in control rats, as did stimulation with cholera toxin (which activates the stimulatory guanine nucleotide binding protein G(s)). The effect of pertussis toxin was abolished following chronic lithium, whereas the increase in cyclic AMP after cholera toxin was enhanced. In vitro pertussis toxin-catalyzed ADP ribosylation of alpha(i) (and alpha(o)) was increased by 20% in prefrontal cortex from lithium-treated rats, but the alpha(i) and alpha(s) contents (as determined by immunoblot) as well as the cholera toxin-catalyzed ADP ribosylation of alpha(s) were unchanged. Taken together, these results suggest that chronic lithium administration may interfere with the dissociation of G(i) into its active components and thereby remove a tonic inhibitory influence on adenylate cyclase, with resultant enhanced basal and cholera toxin-stimulated adenylate cyclase activity. RP MASANA, MI (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BLDG 10,ROOM 2D46,BETHESDA,MD 20892, USA. NR 19 TC 70 Z9 72 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1992 VL 59 IS 1 BP 200 EP 205 DI 10.1111/j.1471-4159.1992.tb08891.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA HZ290 UT WOS:A1992HZ29000024 PM 1319465 ER PT J AU MORGANTIKOSSMANN, MC KOSSMANN, T BRANDES, ME MERGENHAGEN, SE WAHL, SM AF MORGANTIKOSSMANN, MC KOSSMANN, T BRANDES, ME MERGENHAGEN, SE WAHL, SM TI AUTOCRINE AND PARACRINE REGULATION OF ASTROCYTE FUNCTION BY TRANSFORMING GROWTH-FACTOR-BETA SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE ASTROCYTE; TRANSFORMING GROWTH FACTOR-BETA; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR; CHEMOTAXIS; PROLIFERATION ID CENTRAL-NERVOUS-SYSTEM; TUMOR NECROSIS FACTOR; CEREBROSPINAL-FLUID; MESSENGER-RNA; TGF-BETA; CELLS; EXPRESSION; RECEPTOR; BRAIN; LIPOPOLYSACCHARIDE AB Recent evidence indicates that astrocytes have a wide range of functions, usually attributed to cells of the immune system, which are critical for maintaining a balanced homeostatic environment in the central nervous system (CNS). Moreover, these cells are known to participate in inflammatory events within the CNS by secreting cytokines such as transforming growth factor-beta (TGF-beta). In this study we have investigated the ability of TGF-beta to influence astrocyte functions. TGF-beta-1 mRNA is constitutively expressed by astrocytes in vitro, and when cultures are stimulated with exogenous TGF-beta-1 an increase in the expression of this mRNA can be shown, suggesting both autocrine and paracrine regulation. In in vitro assays, TGF-beta-1 is chemotactic for astrocytes in a dose-dependent fashion and inhibits astrocyte proliferation. These results indicating signal transduction by TGF-beta-1-prompted studies to explore receptor-ligand interactions on isolated astrocyte populations. In a receptor binding assay, we demonstrate that astrocytes appear to express three distinct TGF-beta receptor subtypes with nearly 10000 receptors per cell. Thus, TGF-beta may play an important role in regulating astrocyte functions pivotal to the evolution of intracerebral immune responses including recruitment and activation of glial cells at local inflammatory sites within the CNS. C1 NIDR, IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30, ROOM 326, BETHESDA, MD 20892 USA. NR 45 TC 84 Z9 86 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 JUL PY 1992 VL 39 IS 1-2 BP 163 EP 174 DI 10.1016/0165-5728(92)90185-N PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA JB483 UT WOS:A1992JB48300017 PM 1320057 ER PT J AU ROY, JP KOMATSU, H WURTZ, RH AF ROY, JP KOMATSU, H WURTZ, RH TI DISPARITY SENSITIVITY OF NEURONS IN MONKEY EXTRASTRIATE AREA MST SO JOURNAL OF NEUROSCIENCE LA English DT Article ID TEMPORAL VISUAL AREA; PURSUIT EYE-MOVEMENTS; MACAQUE MONKEY; EXPANSION CONTRACTION; FUNCTIONAL-PROPERTIES; ROTATION CELLS; RHESUS-MONKEY; DORSAL PART; CORTEX; MT AB We tested the disparity sensitivity of neurons from the medial superior temporal area (MST) in awake behaving monkeys. While the monkey looked at a fixation spot on a screen in front of it, random dot stimuli moved in the preferred direction of the cell under study, and the disparity of the dots made the stimuli appear to move in a frontoparallel plane in front of, on, or behind the screen. Over 90% of the 272 neurons studied were sensitive to the disparity of the visual stimulus. Of those disparity-sensitive cells, 95% were most responsive either to near stimuli (stimuli with crossed disparities appearing to move in front of the screen) or to far stimuli (stimuli with uncrossed disparities appearing to move behind the screen). In a smaller sample of the disparity-sensitive cells, we found cells whose preferred direction of stimulus motion reversed as the disparity of the stimulus reversed. For example, a cell that responded best to rightward motion for near stimuli responded best to leftward motion for far stimuli. We found that 40% of the disparity-sensitive cells had this disparity-dependent direction selectivity. This disparity-dependent direction selectivity was maintained over the entire range of speeds tested (6-56-degrees/sec). We tested whether the disparity sensitivity of the neurons indicated the distance of the stimulus from the screen where the monkey was fixating (relative depth) or the distance of the stimulus from the monkey (absolute depth) by having the monkey fixate at different depths in front of or behind the screen. For most MST neurons, the changes in vergence did not alter the disparity response, indicating that the disparity sensitivity of these neurons conveyed information on depth relative to the plane of fixation. We conclude that the disparity characteristics of cells in the dorsomedial MST are those expected of a system serving primarily coarse rather than fine stereopsis. The correlation between disparity selectivity and direction selectivity in these neurons, as well as their other properties, suggests a role in signaling the direction of self-motion of the observer through the environment. C1 NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C101,BETHESDA,MD 20892. MONTREAL NEUROL HOSP & INST,DEPT NEUROL & NEUROSURG,MONTREAL H3A 2B4,QUEBEC,CANADA. NR 42 TC 181 Z9 184 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1992 VL 12 IS 7 BP 2478 EP 2492 PG 15 WC Neurosciences SC Neurosciences & Neurology GA JC512 UT WOS:A1992JC51200004 PM 1613542 ER PT J AU NOGUCHI, K RUDA, MA AF NOGUCHI, K RUDA, MA TI GENE-REGULATION IN AN ASCENDING NOCICEPTIVE PATHWAY - INFLAMMATION-INDUCED INCREASE IN PREPROTACHYKININ MESSENGER-RNA IN RAT LAMINA-I SPINAL PROJECTION NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DORSAL HORN NEURONS; INSITU HYBRIDIZATION HISTOCHEMISTRY; SPINOTHALAMIC TRACT CELLS; PRIMARY SENSORY NEURONS; LOWER BRAIN-STEM; SUBSTANCE-P; NEUROKININ-A; PARABRACHIAL NUCLEUS; IMMUNOCYTOCHEMICAL IDENTIFICATION; SPINOMESENCEPHALIC TRACT AB Tachykinin peptides are distributed widely in the nervous system and have been shown to play a prominent role in nociceptive pathways in the spinal cord and dorsal root ganglia. This study investigated the inflammation-induced response of dorsal horn projection neurons and local circuit neurons expressing preprotachykinin (PPT) mRNA using RNA blot analysis and in situ hybridization histochemistry. To identify projection neurons, fluorogold was injected into the parabrachial area of the brainstem. In laminae I, II and V/VI ipsilateral to inflammation, there was a differential increase in the number of neurons exhibiting PPT mRNA. In lamina I, the number of spinal projection neurons containing PPT mRNA showed a greater than 200% increase. The identification of spinal projection neurons with inflammation-induced increases in PPT mRNA suggests that tachykinin peptides may act as neurotransmitters in nociceptive CNS projection path ways. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,ROOM B-20,BETHESDA,MD 20892. NR 69 TC 90 Z9 90 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1992 VL 12 IS 7 BP 2563 EP 2572 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JC512 UT WOS:A1992JC51200013 PM 1613548 ER PT J AU HESS, EJ JINNAH, HA KOZAK, CA WILSON, MC AF HESS, EJ JINNAH, HA KOZAK, CA WILSON, MC TI SPONTANEOUS LOCOMOTOR HYPERACTIVITY IN A MOUSE MUTANT WITH A DELETION INCLUDING THE SNAP GENE ON CHROMOSOME-2 SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ATTENTION DEFICIT DISORDER; ANIMAL-MODEL; EXPRESSION; CHILDREN; BEHAVIOR; MARKERS; FAMILY; RAT AB The gene encoding the synaptosomal-associated protein-25 kDa (SNAP-25) was mapped by analysis of somatic cell hybrids and an intersubspecies backcross to mouse Chromosome 2. To identify potential mutants for SNAP-25, mice bearing mutations mapping to this region of Chromosome 2 were screened for Snap gene abnormalities. Mice heterozygous for the semidominant mutation coloboma (Cm/+) were identified that carried a deletion of Snap gene sequence. Analysis of genomic DNA revealed that the Snap gene dosage in Cm/+ mice was 50% lower than control littermates. Additionally, SNAP-25 mRNA and protein expression were 50% lower in coloboma mice than control littermates. The coloboma mouse phenotype is characterized by small eyes and head bobbing; in addition, we observed that these mice were extremely hyperactive with spontaneous locomotor activity exceeding three times control mouse activity. The localization of the genetic abnormality in coloboma mice using the Snap gene marker will provide a powerful tool for studying the biologic basis of locomotor hyperactivity. C1 Scripps Res Inst, DEPT NEUROPHARMACOL, 10666 N TORREY PINE RD CVN9, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, SCH MED, DEPT NEUROSCI, LA JOLLA, CA 92093 USA. NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 33730]; NINDS NIH HHS [NS 23038]; PHS HHS [07456] NR 36 TC 101 Z9 101 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1992 VL 12 IS 7 BP 2865 EP 2874 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JC512 UT WOS:A1992JC51200037 PM 1613559 ER PT J AU WADHWANI, KC SHIMONHOPHY, M RAPOPORT, SI AF WADHWANI, KC SHIMONHOPHY, M RAPOPORT, SI TI ENHANCED PERMEABILITIES OF CATIONIZED-BOVINE SERUM ALBUMINS AT THE BLOOD-NERVE AND BLOOD-BRAIN BARRIERS IN AWAKE RATS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE PERIPHERAL NERVE; PERMEABILITY; SCIATIC NERVE; CAPILLARY ENDOTHELIAL CELLS; RAT ID POLY-L-LYSINE; PERIPHERAL-NERVE; ANIONIC SITES; FACILITATED TRANSPORT; GLYCOSYLATED ALBUMIN; ENDOTHELIAL-CELLS; LUMINAL SURFACE; CAPILLARIES; CHARGE; PROTEIN AB Permeability-surface area products (PAs) of the blood-nerve barrier (BNB) and blood-brain barrier (BBB) to I-125-labeled native bovine serum albumin (nBSA, pI approximately 4), and to 2 cationized albumins (cBSA) of differing pI (pI approximately 8 and 11), were quantitatively determined in awake rats, using an i.v. bolus injection technique. Mean PAs of the BNB and BBB to I-125-nBSA, after a circulation time of up to 120 min, were (0.17 +/- 0.23) and (0.09 +/- 0.05) x 10(-5) ml/s.g. wet wt, respectively (n = 12 rats), and were not significantly different from 0 (P > 0.05). Mean PAs of the BNB and BBB to I-125-cBSA (pI approximately 8), after circulation time of 12 min, were (1.9 +/- 0.1) and (1.7 +/- 0.1) x 10(-5) ml/s.g wet wt, respectively (n = 8). Significant greater PAs, at both the BNB and BBB to I-125-cBSA (pI approximately 11) [(8.2 +/- 1.8) and (3.0 +/- 0.6) x 10(-5) ml/s.g wet wt, respectively (n = 12)], than both PA's of nBSA and cBSA (pI approximately 8) were found. The accumulation of I-125-cBSA in epi-perineurial tissues also was higher than that of I-125-nBSA, and was related to the degree of cationization. Our results indicate that, as at the BBB, the transfer of cationized serum albumin is enhanced over that of native albumin at the BNB of the mammalian peripheral nerve. RP WADHWANI, KC (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C103,BETHESDA,MD 20892, USA. NR 45 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL PY 1992 VL 32 IS 3 BP 407 EP 414 DI 10.1002/jnr.490320312 PG 8 WC Neurosciences SC Neurosciences & Neurology GA JC608 UT WOS:A1992JC60800011 PM 1433388 ER PT J AU CHANDRASEKARAN, K STOLL, J GIORDANO, T ATACK, JR MATOCHA, MF BRADY, DR RAPOPORT, SI AF CHANDRASEKARAN, K STOLL, J GIORDANO, T ATACK, JR MATOCHA, MF BRADY, DR RAPOPORT, SI TI DIFFERENTIAL EXPRESSION OF CYTOCHROME-OXIDASE (COX) GENES IN DIFFERENT REGIONS OF MONKEY BRAIN SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE FRONTAL CORTEX; CDNA LIBRARY; CYTOCHROME OXIDASE; SYNAPSES; DENDRITES; OXIDATIVE METABOLISM ID MESSENGER-RNAS; ALZHEIMERS-DISEASE; C-OXIDASE; HISTOCHEMICAL-CHANGES; CEREBRAL-CORTEX; GROWTH-FACTOR; CLONING; ASSOCIATION; METABOLISM; NEOCORTEX AB A frontal pole cDNA library from monkey (Macaca mulatta) brain was screened to identify mRNAs that are expressed more in frontal pole as compared to primary visual cortex. Three cDNA clones, whose greater expression was confirmed by Northern blot analysis, were identified as cytochrome oxidase (COX) subunits I, II, and III (COX I, II, and III). Each clone showed higher levels of mRNA in the frontal pole, dorsal lateral prefrontal cortex, and hippocampus than in the primary visual or somatosensory cortices. COX histochemistry of prefrontal, visual, and somatosensory cortical regions demonstrated heterogeneous distributions, with highest activity in dendrite-rich neuropil of the cortex. A laminar distribution of COX mRNA expression also was demonstrated with in situ hybridization. mRNA was detected in cell bodies and in apical dendrites. These results indicate region specific differences in the distribution of COX activity and in the corresponding mRNA for three of its subunits within the monkey brain. Such differences may be related to differences in the distribution of neuropil as compared with cell bodies among the brain regions studied, and may be relevant to selective vulnerability in Alzheimer's disease. RP CHANDRASEKARAN, K (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C 103,BETHESDA,MD 20892, USA. NR 43 TC 33 Z9 33 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL PY 1992 VL 32 IS 3 BP 415 EP 423 DI 10.1002/jnr.490320313 PG 9 WC Neurosciences SC Neurosciences & Neurology GA JC608 UT WOS:A1992JC60800012 PM 1279190 ER PT J AU KITTUR, SD SONG, L ENDO, H ADLER, WH AF KITTUR, SD SONG, L ENDO, H ADLER, WH TI NERVE GROWTH-FACTOR RECEPTOR GENE-EXPRESSION IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES IN AGING SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE MESSENGER RNA; IMMUNE SYSTEM; P75NGFR ID MESSENGER-RNA EXPRESSION; INTERLEUKIN-2 RECEPTOR; NEUROTROPHIC FACTOR; MONONUCLEAR-CELLS; OPIATE RECEPTORS; FACTOR FAMILY; MAST-CELLS; RAT; BRAIN; NGF AB Nerve growth factor (NGF) has a modulating effect on immune function, which may occur as a consequence of binding to the NGF receptor (NGF-R). To determine if mRNA for the gene coding for p75NGFR (low affinity NGF-R) is present in lymphocytes, Northern blot analysis of mRNA from human peripheral blood lymphocytes (PBL) and purified T lymphocytes was initiated using cDNA probe for human p75NGFR. p75NGFR mRNA was present in PBL and T lymphocytes, and the mRNA in response to phytohemagglutinin stimulation showed maximum levels at 14 hr of stimulation. p75NGFR mRNA content when analyzed in PBL and T cells from volunteers of various ages showed that p75NGFR mRNA expression does not change with the age of the cell donor. C1 NIA,MOLEC NEUROBIOL SECT,BALTIMORE,MD 21224. NIA,IMMUNOL SECT,BALTIMORE,MD 21224. NR 37 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUL PY 1992 VL 32 IS 3 BP 444 EP 448 DI 10.1002/jnr.490320316 PG 5 WC Neurosciences SC Neurosciences & Neurology GA JC608 UT WOS:A1992JC60800015 PM 1433390 ER PT J AU DOUDET, DJ MCLELLAN, CA AIGNER, TG WYATT, RJ COHEN, RM AF DOUDET, DJ MCLELLAN, CA AIGNER, TG WYATT, RJ COHEN, RM TI DELAYED L-PHENYLALANINE INFUSION ALLOWS FOR SIMULTANEOUS KINETIC-ANALYSIS AND IMPROVED EVALUATION OF SPECIFIC-TO-NONSPECIFIC FLUORINE-18-DOPA UPTAKE IN BRAIN SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; TIME UPTAKE DATA; PARKINSONS-DISEASE; GRAPHICAL EVALUATION; TRANSFER CONSTANTS; METABOLISM; MONKEYS; MPTP; SYSTEM; HUMANS AB The accumulation of 3-O-methyl-6-[F-18]fluoro-L-DOPA (F-18-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during F-18-DOPA positron emission tomography scanning. To increase the sensitivity of F-18-DOPA for imaging presynaptic dopamine systems, we took advantage of F-18-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after F-18-DOPA administration, prevents F-18-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of F-18 accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in F-18-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NIMH,IRP,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892. RP DOUDET, DJ (reprint author), NIMH,IRP,LCM,CLIN BRAIN IMAGING SECT,BLDG 10-4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 9 Z9 9 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1992 VL 33 IS 7 BP 1383 EP 1389 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JB807 UT WOS:A1992JB80700026 PM 1613582 ER PT J AU BHAT, M NELSON, KB CUMMINS, SK GRETHER, JK AF BHAT, M NELSON, KB CUMMINS, SK GRETHER, JK TI PREVALENCE OF DEVELOPMENTAL ENAMEL DEFECTS IN CHILDREN WITH CEREBRAL-PALSY SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE CEREBRAL PALSY; DENTAL ENAMEL; ENAMEL DEFECTS; ENAMEL HYPOPLASIA AB Enamel defects observed in primary anterior teeth of 123 children with congenital cerebral palsy (CP) born 1983 through 1985 in four northern California counties were categorized using an adaptation of the Developmental Defects of Enamel Index. Nineteen children (15%) had crowns or loss of tooth substance (LTS) due to attrition. Missing enamel (ME) including horizontal groove, was observed in 39 children (32%). Twenty-four children without ME (20%) had enamel pits, vertical grooves, or colored enamel opacities. Forty-one (33%) had clinically normal enamel. ME children did not differ significantly from those with normal enamel with respect to race, sex, singleton vs twin, severity or type of CP, or presence of dysmorphic features. ME children more often had shorter gestational ages than children with normal enamel. More ME children, even those who were not low in birth weight, were reported by parents to have required neonatal intensive care. C1 NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. CALIF DEPT HLTH SERV,CALIF BIRTH DEFECTS MONITORING PROGRAM,EMERYVILLE,CA. CALIF DEPT HLTH SERV,ENVIRONM EPIDEMIOL & TOXICOL BRANCH,EMERYVILLE,CA. RP BHAT, M (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,5333 WESTBARD AVE,ROOM 549,BETHESDA,MD 20816, USA. NR 9 TC 7 Z9 8 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD JUL PY 1992 VL 21 IS 6 BP 241 EP 244 DI 10.1111/j.1600-0714.1992.tb01003.x PG 4 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA JE871 UT WOS:A1992JE87100001 PM 1501154 ER PT J AU HUMAYUN, M BERNSTEIN, SL GOULD, HB CHAVIS, RM AF HUMAYUN, M BERNSTEIN, SL GOULD, HB CHAVIS, RM TI ORBITAL CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA AS THE INITIAL PRESENTATION SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article C1 NEI,BLDG 6,ROOM 224,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0191-3913 J9 J PEDIATR OPHTHALMOL JI J. Pediatr. Ophthalmol. Strabismus. PD JUL-AUG PY 1992 VL 29 IS 4 BP 252 EP 254 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA JK328 UT WOS:A1992JK32800014 PM 1512670 ER PT J AU PHILSTROM, BL KINGMAN, A CHILTON, NW IMREY, PB COHEN, M DAGOSTINO, RB HOBERMAN, D FLEISS, JL HOROWITZ, HS PROSKIN, HM LASTER, LL TRUMMEL, CL CATON, J AF PHILSTROM, BL KINGMAN, A CHILTON, NW IMREY, PB COHEN, M DAGOSTINO, RB HOBERMAN, D FLEISS, JL HOROWITZ, HS PROSKIN, HM LASTER, LL TRUMMEL, CL CATON, J TI BIOLOGICAL AND MEASUREMENT ISSUES CRITICAL TO DESIGN OF GINGIVITIS TRIALS (BRIEF SUMMARY OF COMMON GROUND) - GENERAL DISCUSSION SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Discussion C1 NIDR,BETHESDA,MD 20892. TASK FORCE DESIGN & ANAL,LAWRENCEVILLE,NJ. UNIV ILLINOIS,URBANA,IL 61801. USN DENT RES,GREAT LAKES,IL. BOSTON UNIV,BOSTON,MA 02215. US FDA,ROCKVILLE,MD 20857. COLUMBIA UNIV,NEW YORK,NY 10027. EASTMAN DENT CTR,ROCHESTER,NY 14620. UNIV PENN,PHILADELPHIA,PA 19104. UNIV CONNECTICUT,STORRS,CT 06268. RP PHILSTROM, BL (reprint author), UNIV MINNESOTA,MINNEAPOLIS,MN 55455, USA. NR 1 TC 0 Z9 0 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUL PY 1992 VL 27 IS 4 BP 373 EP 377 PN 2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JF125 UT WOS:A1992JF12500018 ER PT J AU KINGMAN, A AF KINGMAN, A TI SPECIFIC STATISTICAL CONSIDERATIONS RELEVANT TO THE DESIGN AND ANALYSIS OF GINGIVITIS TRIALS DEMONSTRATING PRODUCT SUPERIORITY OR EQUIVALENCE SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article; Proceedings Paper CT CONF ON EQUIVALENCY AND SUPERIORITY CLAIMS FOR PRODUCTS FOR GINGIVITIS AND PERIODONTITIS CY MAY 14-16, 1991 CL CHICAGO, IL SP ATRIX LABS, CHESEBROUGH PONDS, CHURCH & DWIGHT, COLGATE PALMOLIVE, JOHNSON & JOHNSON CONSUMER PROD, ORAL B LABS, PROTER & GAMBLE, SMITHKLINE BEECHAM CONSUMER PROD, UNILEVER RES, VIPONT PHARM DE SUPERIORITY; EQUIVALENCE; DESIGN; ANALYSIS ID CLINICAL-TRIALS; DENTAL PLAQUE; MOUTHRINSES; BIOAVAILABILITY; BIOEQUIVALENCE; CHLORHEXIDINE; EFFICACY AB Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence - denoted "least as good" - was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The "least as good" alternative to "equivalence" makes it easier to demonstrate "equivalence" for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for test products not quite as good as the active control. RP KINGMAN, A (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 37 TC 7 Z9 7 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUL PY 1992 VL 27 IS 4 BP 378 EP 389 DI 10.1111/j.1600-0765.1992.tb01701.x PN 2 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JF125 UT WOS:A1992JF12500019 PM 1507027 ER PT J AU KINGMAN, A HOBERMAN, D ZIMMERMAN, S FLEISS, JL LASTER, LL HORROWITZ, HS IMREY, PB WOODALL, I DAGOSTINO, RB PIHLSTROM, BL POLSON, AM CLARK, W JEFFCOAT, M CRAWFORD, JM VINCENT, JW CHILTON, NW AF KINGMAN, A HOBERMAN, D ZIMMERMAN, S FLEISS, JL LASTER, LL HORROWITZ, HS IMREY, PB WOODALL, I DAGOSTINO, RB PIHLSTROM, BL POLSON, AM CLARK, W JEFFCOAT, M CRAWFORD, JM VINCENT, JW CHILTON, NW TI ISSUES OF INDIVIDUAL STUDY ANALYSIS AND SYNTHESIS OF STUDIES SPECIFIC TO EVALUATION OF STUDIES OF PERIODONTITIS - GENERAL DISCUSSION SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Discussion C1 US FDA,ROCKVILLE,MD 20857. UNIV TEXAS,HOUSTON,TX 77025. COLUMBIA UNIV,NEW YORK,NY 10027. UNIV PENN,PHILADELPHIA,PA 19104. UNIV ILLINOIS,COLL DENT,URBANA,IL 61801. VIPONT PHARMACEUT INC,FT COLLINS,CO. BOSTON UNIV,BOSTON,MA 02215. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. ATRIX LABS,FT COLLINS,CO. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV ALABAMA,BIRMINGHAM,AL 35294. WARNER LAMBERT PARKE DAVIS,MORRIS PLAINS,NJ. TASK FORCE DESIGN & ANAL,LAWRENCEVILLE,NJ. RP KINGMAN, A (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUL PY 1992 VL 27 IS 4 BP 450 EP 454 PN 2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JF125 UT WOS:A1992JF12500032 ER PT J AU CHEN, HT CLARK, M GOLDMAN, D AF CHEN, HT CLARK, M GOLDMAN, D TI QUANTITATIVE AUTORADIOGRAPHY OF H-3 PAROXETINE BINDING-SITES IN RAT-BRAIN SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE PAROXETINE BINDING; SEROTONIN UPTAKE; QUANTITATIVE AUTORADIOGRAPHY ID SEROTONIN UPTAKE SITES; IMIPRAMINE BINDING; H-3 PAROXETINE; IMIPRAMINE BINDING; LOCALIZATION; MEMBRANES; TRANSPORTER; CITALOPRAM AB The use of H-3-paroxetine as a ligand for quantitative autoradiography of serotonin (5-HT) transport sites was optimized, and the distribution of H-3-paroxetine binding sites in rat brain was studied. Under the conditions described, H-3-paroxetine binding in forebrain sections was of high affinity and saturable, with a Kd of 0. 18 +/- 0.02 nM (mean +/- SEM) and B(max) of 268 +/- 12 fmol/mg of protein (n = 3). Nonspecific binding was 10.7% +/- 1.0 of the total binding (n = 8). The distribution of 3H-paroxetine binding sites closely matched the regional distribution of 5-HT nerve terminals and cell bodies. The highest concentrations of H-3-paroxetine binding sites were found in the dorsal raphe nucleus (563 +/- 55 fmol/mg tissue, n = 4), and high densities of binding were also found in the locus coeruleus, medial forebrain bundle, substantia nigra, several limbic structures (amygdala, hippocampus, hypothalamus, olfactory tubercle, septum, and thalamus), and components of the visual relay system (superior colliculus and the lateral geniculate body). Although lesioning of 5-HT neurons with p-chloroamphetamine (PCA) drastically eliminated H-3-paroxetine binding in most regions of the rat brain, significant binding remained in the raphe nuclei and medial forebrain bundle suggesting that 3H-paroxetine binding in these regions was to presynaptic sites on cell bodies or axons relatively resistant to PCA. C1 NIAAA,CLINICAL STUDIES,BETHESDA,MD. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 24 TC 42 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD JUL PY 1992 VL 27 IS 4 BP 209 EP 216 DI 10.1016/1056-8719(92)90043-Z PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JP169 UT WOS:A1992JP16900003 PM 1421530 ER PT J AU BOWEN, WD WALKER, JM DECOSTA, BR WU, R TOLENTINO, PJ FINN, D ROTHMAN, RB RICE, KC AF BOWEN, WD WALKER, JM DECOSTA, BR WU, R TOLENTINO, PJ FINN, D ROTHMAN, RB RICE, KC TI CHARACTERIZATION OF THE ENANTIOMERS OF CIS-N-[2-(3,4-DICHLOROPHENYL)ETHYL]-N-METHYL-2-(1-PYRROLIDINYL)CYCLOHEXY LAMINE (BD737 AND BD738) - NOVEL COMPOUNDS WITH HIGH-AFFINITY, SELECTIVITY AND BIOLOGICAL EFFICACY AT SIGMA RECEPTORS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; ANTIPSYCHOTIC-DRUGS; OPIATE RECEPTORS; OPIOID RECEPTOR; BINDING-SITES; LIGANDS; RAT; PHENCYCLIDINE; DOPAMINE; AGONIST AB A novel class of compounds with very high affinity and selectivity for sigma receptors has been discovered. BD614 {(+/-)-cis-N-[2-(3,4-dichlorophenyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine} and its optically pure 1S,2R-(-)- [BD737] and 1R,2S-(+)-[BD738]enantiomers bound to sigma receptors of guinea pig brain with K(i) = 2.0 +/- 0.4, 1.3 +/- 0.3 and 6 +/- 3 nM, respectively. These compounds exhibited little or no affinity for dopamine-D2, kappa opiate or phencyclidine receptors and displayed high biological efficacy in assays of sigma receptor function, ability to produce alterations in motor behavior and inhibition of the muscarinic cholinergic phosphoinositide response. Microinjection of BD614 into the rat red nucleus or substantia nigra produced a dose-dependent alteration in head position and contralateral circling, respectively. BD614, BD737 and BD738 inhibited stimulation of inositol phosphate production by carbachol or oxotremorine-M in a dose-dependent manner. Thus, N-substituted cis-2-(1-pyrrolidinyl)cyclohexylamines may prove useful in studies of sigma receptor structure and function. C1 BROWN UNIV,DEPT PSYCHOL,PROVIDENCE,RI 02912. BROWN UNIV,DIV BIOL & MED,BIOCHEM SECT,PROVIDENCE,RI 02912. RP BOWEN, WD (reprint author), NIDDKD,RECEPTOR BIOCHEM & PHARMACOL UNIT,MED CHEM LAB,BLDG 8,RM B1-23,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [DA04988]; NINDS NIH HHS [NS26746] NR 48 TC 32 Z9 33 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1992 VL 262 IS 1 BP 32 EP 40 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JD136 UT WOS:A1992JD13600005 PM 1320690 ER PT J AU KINDERKNECHT, KE WONG, GK BILLY, EJ LI, SH AF KINDERKNECHT, KE WONG, GK BILLY, EJ LI, SH TI THE EFFECT OF A DEPROGRAMMER ON THE POSITION OF THE TERMINAL TRANSVERSE HORIZONTAL AXIS OF THE MANDIBLE SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID HINGE AXIS AB This study measured the amount of positional change in the terminal transverse horizontal axis of the mandible that results from altering undesirable neuromuscular influence. Centric relation records were made on 19 healthy subjects before and after deprogramming. The axis was located with a computerized axiograph, and the centric relation records were compared in vivo at the axis location. The positional change of the axis was quantified in three dimensions at an accuracy of +/-0.05 mm. The net amount of positional change was compared to scores from the temporomandibular joint scale to test for correlation with the potential for developing a temporomandibular disorder. The findings showed that the amount of positional change in the terminal transverse horizontal axis in 18 of 19 healthy patients after 12 hours of deprogramming was less than 0.5 mm and did not correlate with scores from the TMJ Scale. C1 NATL NAVAL DENT CTR,BETHESDA,MD. NIH,BETHESDA,MD 20892. RP KINDERKNECHT, KE (reprint author), UNIV KENTUCKY,COLL DENT,CHANDLER MED CTR,DEPT ORAL HLTH PRACTICE,LEXINGTON,KY 40356, USA. NR 29 TC 6 Z9 8 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUL PY 1992 VL 68 IS 1 BP 123 EP 131 DI 10.1016/0022-3913(92)90300-Y PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JC173 UT WOS:A1992JC17300028 PM 1403902 ER PT J AU TORII, M NAKAMURA, KI SIEBER, KP MILLER, LH AIKAWA, M AF TORII, M NAKAMURA, KI SIEBER, KP MILLER, LH AIKAWA, M TI PENETRATION OF THE MOSQUITO (AEDES-AEGYPTI) MIDGUT WALL BY THE OOKINETES OF PLASMODIUM-GALLINACEUM SO JOURNAL OF PROTOZOOLOGY LA English DT Article DE ELECTRON MICROSCOPY; MALARIA ID EPITHELIUM AB We observed Plasmodium gallinaceum ookinetes in both intracellular and intercellular positions in the midgut epithelium of the mosquito Aedes aegypti. After epithelial cell invasion intracellular ookinetes lacked a parasitophorous vacuolar membrane and were surrounded solely by their own pellicle. Thus, the ookinete in the midgut epithelium of the mosquito differs from erythrocytic and hepatic stages in that the parasite in the vertebrate host is surrounded by a vacuole. The midgut epithelial cytoplasm around the apical end of invading ookinetes was replaced by fine granular material deprived of normal organelles. Membranous structure was observed within the fine granular area. Most ookinetes were seen intracellularly on the luminal side and intercellularly on the haemocoel side of the midgut epithelial cells. These observations suggest that the ookinete first enters into the midgut epithelial cell, then exits to the space between the epithelial cells and moves to the basal lamina where the ookinete develops to the oocyst. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. FU NCCIH NIH HHS [AT-10645] NR 14 TC 41 Z9 42 U1 0 U2 1 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 0022-3921 J9 J PROTOZOOL PD JUL-AUG PY 1992 VL 39 IS 4 BP 449 EP 454 DI 10.1111/j.1550-7408.1992.tb04830.x PG 6 WC Zoology SC Zoology GA JE021 UT WOS:A1992JE02100002 PM 1403980 ER PT J AU BENCHIMOL, M KACHAR, B DESOUZA, W AF BENCHIMOL, M KACHAR, B DESOUZA, W TI SURFACE DOMAINS IN THE PATHOGENIC PROTOZOAN TRITRICHOMONAS-FETUS SO JOURNAL OF PROTOZOOLOGY LA English DT Article DE ELECTRON MICROSCOPY; FLAGELLAR MEMBRANE; FREEZE ETCHING ID RIEDMULLER; MEMBRANE AB The quick-freezing and freeze-etching techniques were used to analyze surface domains of Tritrichomonas foetus. The surface of the protozoan body was not smooth, presenting surface projections, except on the flagellar surface. Images of the actual surface of the anterior flagella revealed the presence of intramembranous particles that form rosettes, as observed on the protoplasmic fracture face. They may represent integral transmembrane proteins exposed at the cell surface. Surface specializations were also observed at the flagella base and where the recurrent flagellum attaches to the cell body. C1 UNIV FED RIO DE JANEIRO,ILHA FD,INST BIOFIS CARLOS CHAGAS FILHO,DEPT PARASITOL & BIOFIS,BR-21941 RIO DE JANEIRO,BRAZIL. UNIV SAO PAULO,ICB,DEPT HISTOL,BR-01051 SAO PAULO,BRAZIL. NIDCD,MOLEC OTOL LAB,BETHESDA,MD 20892. NR 12 TC 13 Z9 13 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 0022-3921 J9 J PROTOZOOL PD JUL-AUG PY 1992 VL 39 IS 4 BP 480 EP 484 DI 10.1111/j.1550-7408.1992.tb04835.x PG 5 WC Zoology SC Zoology GA JE021 UT WOS:A1992JE02100007 PM 1403983 ER PT J AU DYSKEN, MW MINICHIELLO, MD HILL, JL SKARE, S LITTLE, JT MOLCHAN, SE SUNDERLAND, T AF DYSKEN, MW MINICHIELLO, MD HILL, JL SKARE, S LITTLE, JT MOLCHAN, SE SUNDERLAND, T TI DISTRIBUTION OF PERIPHERAL LYMPHOCYTES IN ALZHEIMER PATIENTS AND CONTROLS SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID PRIMARY DEGENERATIVE DEMENTIA; SENILE DEMENTIA; IMMUNOLOGICAL PARAMETERS; PRESENILE-DEMENTIA; DISEASE; IMMUNOGLOBULINS; SUBPOPULATIONS; PLAQUES; INDEXES; SCALE AB Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reponed to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia. C1 NIMH,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BIOSTAT UNIT,BETHESDA,MD 20892. RP DYSKEN, MW (reprint author), VET ADM MED CTR,GERIATR RES EDUC & CLIN CTR PROGRAM 11G,1 VET DR,MINNEAPOLIS,MN 55417, USA. NR 32 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 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUL PY 1992 VL 26 IS 3 BP 213 EP 218 DI 10.1016/0022-3956(92)90024-I PG 6 WC Psychiatry SC Psychiatry GA JT523 UT WOS:A1992JT52300004 PM 1432847 ER PT J AU TSUNODA, T PARRISH, KM HIGUCHI, S STINSON, FS KONO, H OGATA, M HARFORD, TC AF TSUNODA, T PARRISH, KM HIGUCHI, S STINSON, FS KONO, H OGATA, M HARFORD, TC TI THE EFFECT OF ACCULTURATION ON DRINKING ATTITUDES AMONG JAPANESE IN JAPAN AND JAPANESE-AMERICANS IN HAWAII AND CALIFORNIA SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article AB Data from a joint Japan-U.S. collaborative study were examined to determine the relationship of acculturation to drinking attitudes among Japanese in Japan and Japanese Americans in Hawaii and California. Drinking attitudes (i.e., self-reported acceptable or appropriate levels of drinking) among ethnic groups differed significantly for the nine situations studied: (1) at a bar with friends, (2) at a party at someone else's house. (3) as a parent, spending time with small children. (4) during working hours, (5) visiting in-laws, (6) with friends at home. (7) with friends after work, (8) with people at sports events and (9) before driving a car. Factor analysis was used to determine the differences in drinking attitudes among these ethnic groups. Japanese and Japanese Americans differentiated drinking situations into different categories. The major difference between the two groups was that the Japanese associated spending time with small children with a situation appropriate for drinking, such as being with friends at home, whereas Japanese Americans associated spending time with small children with a situation inappropriate for drinking, such as before driving. RP TSUNODA, T (reprint author), NIAAA,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Makimoto, Kiyoko/0000-0003-0242-1290 NR 19 TC 19 Z9 19 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 1992 VL 53 IS 4 BP 369 EP 377 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA HZ750 UT WOS:A1992HZ75000011 PM 1619931 ER PT J AU PETRONE, RK KLUES, HG PANZA, JA PETERSON, EE MARON, BJ AF PETRONE, RK KLUES, HG PANZA, JA PETERSON, EE MARON, BJ TI COEXISTENCE OF MITRAL-VALVE PROLAPSE IN A CONSECUTIVE GROUP OF 528 PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY ASSESSED WITH ECHOCARDIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SYSTOLIC ANTERIOR MOTION; LEFT-VENTRICULAR HYPERTROPHY; MUSCULAR SUBAORTIC STENOSIS; M-MODE ECHOCARDIOGRAPHY; OBSTRUCTIVE CARDIOMYOPATHY; DIMENSIONAL ECHOCARDIOGRAPHY; CLINICAL MANIFESTATIONS; PRESSURE-GRADIENT; PATHO-PHYSIOLOGY; YOUNG-WOMEN AB Hypertrophic cardiomyopathy and mitral valve prolapse are both conditions that may be genetically transmitted and incur a risk for sudden cardiac death. Although the small left ventricular cavity and distorted geometry characteristic of hypertrophic cardiomyopathy might suggest a predisposition to mitral valve prolapse, the frequency with which these two entities coexist and the potential clinical significance of such an association are not known. To further define the relation of hypertrophic cardiomyopathy and mitral valve prolapse, 528 consecutive patients with hypertrophic cardiomyopathy were studied by echocardiography. Patients ranged in age from 1 to 86 years (mean 45); 335 (63%) were male. Unequivocal echocardiographic evidence of systolic mitral valve prolapse into the left atrium was identified in only 16 (3%) of the 528 patients. The mitral valve excised at operation from three of the patients had morphologic characteristics of a floppy mitral valve, which was judged to be responsible for the echocardiographic findings. Occurrence of clinically evident atrial fibrillation was common in patients with hypertrophic cardiomyopathy and mitral valve prolapse (9 [56%] of 16). Hence, in a large group of patients with hypertrophic cardiomyopathy, the association of echocardiographically documented mitral valve prolapse was uncommon. The coexistence of mitral valve prolapse in patients with hypertrophic cardiomyopathy appears to predispose such patients to atrial fibrillation. C1 NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B 15,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 63 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1992 VL 20 IS 1 BP 55 EP 61 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JB300 UT WOS:A1992JB30000009 PM 1607539 ER PT J AU PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V MAUREA, S MARINNETO, JA ARRIGHI, JA FRANK, JA BONOW, RO AF PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V MAUREA, S MARINNETO, JA ARRIGHI, JA FRANK, JA BONOW, RO TI METABOLIC EVIDENCE OF VIABLE MYOCARDIUM IN REGIONS WITH REDUCED WALL THICKNESS AND ABSENT WALL THICKENING IN PATIENTS WITH CHRONIC ISCHEMIC LEFT-VENTRICULAR DYSFUNCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; NUCLEAR MAGNETIC-RESONANCE; CORONARY-ARTERY DISEASE; BLOOD-FLOW; HIBERNATING MYOCARDIUM; F-18 DEOXYGLUCOSE; HEART-DISEASE; N-13 AMMONIA; INFARCTION; MOTION AB Reduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 +/- 10 %) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) >50 % of that in normal regions. Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxyglucose uptake was observed in 97 % of the hypokinetic and normokinetic regions and in 74 % of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 +/- 4 vs. 7 +/- 3 mm, p < 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74 % and 79 %, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end-diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32). Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium. C1 NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B 15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NR 28 TC 72 Z9 73 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1992 VL 20 IS 1 BP 161 EP 168 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JB300 UT WOS:A1992JB30000025 PM 1607518 ER PT J AU SCHERR, PA LACROIX, AZ WALLACE, RB BERKMAN, L CURB, JD CORNONIHUNTLEY, J EVANS, DA HENNEKENS, CH AF SCHERR, PA LACROIX, AZ WALLACE, RB BERKMAN, L CURB, JD CORNONIHUNTLEY, J EVANS, DA HENNEKENS, CH TI LIGHT TO MODERATE ALCOHOL-CONSUMPTION AND MORTALITY IN THE ELDERLY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR MORTALITY; RISK AB Objective: To determine whether there is a relationship of low to moderate alcohol consumption with cardiovascular mortality in the elderly. Design: Prospective cohort studies with 5-year mortality follow-up. Setting: Three populations of community-dwelling elders. Participants: Population-based cohorts of men and women, aged 65 or older, in three populations. Subjects with prior myocardial infarction, stroke, or cancer, as well as those lacking alcohol consumption data, were excluded from statistical analyses leaving 2,694 subjects in East Boston, Massachusetts, 2,293 subjects in Iowa, and 1,904 subjects in New Haven, Connecticut. Main Outcome Measurements: Alcohol consumption, total mortality, cardiovascular mortality, and cancer mortality. Results: Low to moderate alcohol consumption was associated with statistically significant lowered total as well as cardiovascular mortality in East Boston and New Haven. The relative risks of total mortality for low to moderate consumers of alcohol compared to those consuming no alcohol in the previous year were 0.7 (95% CI 0.6-0.8) in East Boston and 0.6 (95% CI 0.5-0.8) in New Haven. For cardiovascular mortality, the RRs were 0.6 in East Boston and 0.5 in New Haven (95% CI's exclude null). These results persisted after control for potential confounding variables. In Iowa, there were no significant differences in total or cardiovascular mortality according to alcohol consumption patterns. For cancer mortality, there were no significant associations with alcohol consumption in any of the three populations. Conclusions: These data suggest that the relationship of low to moderate alcohol consumption with reduced total and cardiovascular mortality, which are well documented in middle age, also occur in older populations. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA. HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. YALE UNIV,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06510. UNIV IOWA HOSP & CLIN,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. UNIV HAWAII MANOA,SCH MED,HONOLULU,HI 96822. HARVARD UNIV,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01605. FU NIA NIH HHS [N01-AG-0-2107, N01-AG-0-2105, N01-AG-0-2106] NR 25 TC 78 Z9 78 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 JUL PY 1992 VL 40 IS 7 BP 651 EP 657 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JC370 UT WOS:A1992JC37000001 PM 1607579 ER PT J AU AKIYAMA, T PAWITAN, Y CAMPBELL, WB PAPA, L BARKER, AH RUBBERT, P FRIEDMAN, L KELLER, M JOSEPHSON, RA AF AKIYAMA, T PAWITAN, Y CAMPBELL, WB PAPA, L BARKER, AH RUBBERT, P FRIEDMAN, L KELLER, M JOSEPHSON, RA TI EFFECTS OF ADVANCING AGE ON THE EFFICACY AND SIDE-EFFECTS OF ANTIARRHYTHMIC DRUGS IN POSTMYOCARDIAL INFARCTION PATIENTS WITH VENTRICULAR ARRHYTHMIAS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ATTACK TRIAL EXPERIENCE; SUPPRESSION; THERAPY AB Objective: To determine the effect of age on the response to anti-arrhythmic drugs. Design: Randomized controlled trial comparing particular drugs. Setting: Multi-institutional (The Cardiac Arrhythmia Suppression Trial, CAST). Participants: 2,371 patients, age <80, with ventricular arrhythmias after a recent myocardial infarction. Subjects classified by age as less-than-or-equal-to 55, 56-65, and 66-79 years. Intervention: Upwardly titrated doses of encainide, flecainide or moricizine. After identification of a tolerated and effective dose of one of the drugs, participants were randomized to that drug and dose versus its placebo for up to 10 months. Main Outcome Measures: Efficacy of drug (suppression of ventricular premature depolarizations and/or non-sustained ventricular tachycardia), side effects and mortality. Results: Older patients had more previous MIs, congestive heart failure (CHF), hypertension, NSVT, repolarization abnormalities, digitalis use, and diuretic use. They had less pathologic Q-waves or electrocardiographic injury pattern, and their left ventricular ejection fraction (LVEF) was lower. First dose VPD suppression with the first drug averaged 53% and is not associated with age (P = 0.29). Adverse events including death are more frequent in older patients taking study drugs (P < 0.001). This trend is consistent in all three study drugs and at varying LVEFs. History of prior MI, low LVEF, VPD (in log scale), and digitalis therapy also correlates with adverse events (all P < 0.05). Following adjustment for these factors, older age is an independent predictor of adverse events (relative risk 1.30 per decade of age, P < 0.001). Conclusions: Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents. C1 UNIV MED & DENT NEW JERSEY, SCH OSTEOPATH MED, DEPT MED, STRATFORD, NJ USA. SALT LAKE CLIN RES FDN, SALT LAKE CITY, UT USA. AKRON CITY HOSP, DEPT MED, AKRON, OH USA. VANDERBILT UNIV, ST THOMAS HOSP, DIV CARDIOL, NASHVILLE, TN 37240 USA. NHLBI, CLIN APPLICAT & PREVENT PROGRAM, BETHESDA, MD 20892 USA. UNIV WASHINGTON, CTR CARDIAC ARRYTHMIA SUPPRESSION TRIAL, SEATTLE, WA 98195 USA. MIRIAM HOSP, PROVIDENCE, RI 02906 USA. NORTHEASTERN OHIO UNIV, COLL MED, ROOTSTOWN, OH 44272 USA. RP AKIYAMA, T (reprint author), UNIV ROCHESTER, DEPT MED, CARDIOL UNIT, BOX 679, 601 ELMWOOD AVE, ROCHESTER, NY 14642 USA. NR 8 TC 28 Z9 29 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1992 VL 40 IS 7 BP 666 EP 672 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JC370 UT WOS:A1992JC37000004 PM 1607582 ER PT J AU PARKER, CE PERKINS, JR TOMER, KB SHIDA, Y OHARA, K KONO, M AF PARKER, CE PERKINS, JR TOMER, KB SHIDA, Y OHARA, K KONO, M TI APPLICATION OF NANOSCALE PACKED CAPILLARY LIQUID-CHROMATOGRAPHY (75 MU-M ID) AND CAPILLARY ZONE ELECTROPHORESIS ELECTROSPRAY IONIZATION MASS-SPECTROMETRY TO THE ANALYSIS OF MACROLIDE ANTIBIOTICS SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID FAST-ATOM-BOMBARDMENT; ESCHERICHIA-COLI; ERYTHROMYCIN ESTERASE; ATMOSPHERIC-PRESSURE; GLASS-CAPILLARIES; HIGHLY RESISTANT; INNER DIAMETERS; INTERFACE; PROTEINS; STRAIN AB Nanoscale separation techniques, nanoscale packed capillary columns (75-mu-m id), and capillary zone electrophoresis (CZE), on-line with electrospray mass spectrometry (ESI/MS), were applied to the separation of a series of ten macrolide antibiotics. Both techniques use sub-microliter-per-minute flow rates through the analytical column and therefore require an electrospray probe that incorporates coaxial sheath flow. Positive ion electrospray mass spectra of these compounds yielded mainly protonated molecules. Fragmentation to yield structurally significant fragment ions was achieved by collision-induced dissociation (CID) at increased skimmer voltages. Separations were achieved using both techniques, with CZE/ESI/MS showing improved peak shapes and detection limits combined with faster analysis times. Nanoscale packed capillary columns provided better chromatographic resolution and was less susceptible to peak broadening caused by overloading of the analytes. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. TOKYO COLL PHARM,DEPT MICROBIOL,TOKYO 110,JAPAN. TOKYO COLL PHARM,DEPT CHEM ANAL,TOKYO 110,JAPAN. RI Tomer, Kenneth/E-8018-2013 NR 63 TC 46 Z9 46 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUL PY 1992 VL 3 IS 5 BP 563 EP 574 DI 10.1016/1044-0305(92)85034-H PG 12 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA JB461 UT WOS:A1992JB46100011 PM 24234500 ER PT J AU KILBOURN, RG GROSS, SS LODATO, RF ADAMS, J LEVI, R MILLER, LL LACHMAN, LB GRIFFITH, OW AF KILBOURN, RG GROSS, SS LODATO, RF ADAMS, J LEVI, R MILLER, LL LACHMAN, LB GRIFFITH, OW TI INHIBITION OF INTERLEUKIN-1-ALPHA-INDUCED NITRIC-OXIDE SYNTHASE IN VASCULAR SMOOTH-MUSCLE AND FULL REVERSAL OF INTERLEUKIN-1-ALPHA-INDUCED HYPOTENSION BY N-OMEGA-AMINO-L-ARGININE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-NECROSIS-FACTOR; METHYL-L-ARGININE; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; NITROGEN-OXIDES; RELAXING FACTOR; BLOOD-PRESSURE; INTERLEUKIN-1; MACROPHAGE; ENDOTOXIN AB Background: Interleukin-1-alpha (IL-1) is a cytokine with potentially therapeutic immunoproliferative and tumoricidal activities. Preliminary clinical studies suggest that use of IL-1 may be restricted by dose-limiting hypotension. Purpose: The purpose of this study was to investigate the role of nitric oxide (NO.) as a possible mediator of this hypotension. Methods: Cytokine-treated rat aortic smooth muscle cells were assayed for nitrite production, a stable breakdown product of nitric oxide. Nitric oxide synthase from smooth muscle cells was partially characterized in cytosol preparations using a novel Fe2+-myoglobin method to test for nitric oxide production. To determine the role of NO. on the immunorestorative and antineoplastic activity of IL-1, N(omega)-amino-L-arginine (NAA) or N(omega)-monomethyl-L-arginine (NMA), inhibitors of nitric oxide synthase, were added to either cultures of IL-1-dependent T cells or A375 melanoma cells exposed to IL-1. To investigate the effects of NAA in vivo, pentobarbital anesthetized dogs, which were made hypotensive by administration of IL-1, received a single intravenous bolus dose of NAA. The effects of NAA were then reversed by the administration of L-arginine. Results: Our results show that cultured IL-1-activated rat aortic smooth muscle cells synthesize nitric oxide, a potent vasodilator. Induction of nitric oxide synthase is augmented by interferon-gamma and blocked by IL-1 receptor antagonist and by inhibitors of RNA or protein synthesis. Nitric oxide synthesis by IL-1-activated smooth muscle cells is inhibited by NAA, NMA, and N(omega)-nitro-L-arginine (NNA) with ED50 (i.e., effective dose for 50% inhibition) values of 20, 60, and 1000-mu-M, respectively; this rank order of inhibition is characteristic of an agonist-unregulated, inducible isoform of nitric oxide synthase. In smooth muscle cells, inhibition of NO. synthesis by NAA is reversed by excess L-arginine. Consistent with the induction of unregulated NO. synthesis in vascular smooth muscle in vivo, administration of IL-1 (50-mu-g/kg) to dogs caused a 33.5% decrease in systemic vascular resistance and a 28% decrease in blood pressure within 3 hours. Subsequent administration of NAA (20 mg/kg) rapidly and completely reversed the hypotension and increased systemic vascular resistance; these effects of NAA were reversed by L-arginine. Neither the immunoproliferative nor the tumoricidal activity of IL-1 was diminished by NAA. Conclusions: Our results indicate that (a) vascular smooth muscle is a likely source as well as a target of IL-1-induced NO. synthesis, causing vasodilatation and hypotension, (b) nitric oxide synthase inhibitors can fully reverse this hypotension, and (c) the therapeutically useful properties of IL-1 are not diminished by nitric oxide synthase inhibitors. Implications: Administration of inhibitors of nitric oxide synthase can reverse the pathological cardiovascular effects of IL-1 at concentrations that do not interfere with the potentially useful immunoproliferative or tumoricidal effects of this cytokine. In the context of the current clinical trials of IL-1, this finding would represent a very significant advantage. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030. NCI,DIV CANC TREATMENT,CANC THERAPY & EVALUAT PROGRAM,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,COLL MED,DEPT PHARMACOL,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,DEPT BIOCHEM,NEW YORK,NY 10021. UNIV TEXAS,HLTH SCI CTR,DIV PULM & CRIT CARE MED,HOUSTON,TX 77225. RP KILBOURN, RG (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED ONCOL,BOX 13,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HL-34215, HL-46403]; NIDDK NIH HHS [DK-37116] NR 55 TC 74 Z9 74 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 JUL 1 PY 1992 VL 84 IS 13 BP 1008 EP 1016 DI 10.1093/jnci/84.13.1008 PG 9 WC Oncology SC Oncology GA JA762 UT WOS:A1992JA76200011 PM 1376778 ER PT J AU WELLER, M AF WELLER, M TI ELEVATED LEVELS OF FIBRONECTIN IN THE CSF - WHAT DO THEY SIGNIFY SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Letter ID CENTRAL NERVOUS-SYSTEM; PROTEIN RP WELLER, M (reprint author), NIH,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 3N256,BETHESDA,MD 20892, USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUL PY 1992 VL 110 IS 1-2 BP 232 EP 233 DI 10.1016/0022-510X(92)90033-H PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JD132 UT WOS:A1992JD13200032 PM 1506864 ER PT J AU FIERER, DS CHALLBERG, MD AF FIERER, DS CHALLBERG, MD TI PURIFICATION AND CHARACTERIZATION OF UL9, THE HERPES-SIMPLEX VIRUS TYPE-1 ORIGIN-BINDING PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID ENCODED DNA-POLYMERASE; GENE-PRODUCT; COOPERATIVE BINDING; PUTATIVE HELICASES; REPLICATION ORIGIN; ESCHERICHIA-COLI; SITES; IDENTIFICATION; REPRESSOR; CLONING AB UL9, the origin-binding protein of herpes simplex virus type 1 (HSV-1), has been overexpressed in an insect cell overexpression system and purified to homogeneity. In this report, we confirm and extend recent findings on the physical properties, enzymatic activities, and binding properties of UL9. We demonstrate that UL9 exists primarily as a homodimer in solution and that these dimers associate to form a complex nucleoprotein structure when bound to the HSV origin of replication. We also show that UL9 is an ATP-dependent helicase, capable of unwinding partially duplex DNA in a sequence-independent manner. Although the helicase activity of UL9 is demonstrable on short duplex substrates in the absence of single-stranded DNA-binding proteins, the HSV single-stranded DNA-binding protein ICP8 (but not heterologous binding proteins) stimulates UL9 to unwind long DNA sequences of over 500 bases. We were not able to demonstrate unwinding of fully duplex DNA sequences containing the HSV origin of replication. However, in experiments designed to detect origin-dependent unwinding, we did find that UL9 wraps supercoiled DNA independent of sequence or ATP hydrolysis. C1 NIAID,VIRAL DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 54 TC 88 Z9 88 U1 3 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 3986 EP 3995 PG 10 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600002 PM 1318393 ER PT J AU PERRY, ST FLAHERTY, MT KELLEY, MJ CLABOUGH, DL TRONICK, SR COGGINS, L WHETTER, L LENGEL, CR FULLER, F AF PERRY, ST FLAHERTY, MT KELLEY, MJ CLABOUGH, DL TRONICK, SR COGGINS, L WHETTER, L LENGEL, CR FULLER, F TI THE SURFACE ENVELOPE PROTEIN GENE REGION OF EQUINE INFECTIOUS-ANEMIA VIRUS IS NOT AN IMPORTANT DETERMINANT OF TROPISM INVITRO SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEQUENCE-ANALYSIS; PERSISTENT INFECTION; NUCLEOTIDE-SEQUENCE; ANTIGENIC VARIATION; MOLECULAR CLONE; CELL TROPISM; VARIANTS; DNA; EIAV AB Virulent, wild-type equine infectious anemia virus (EIAV) is restricted in one or more early steps in replication in equine skin fibroblast cells compared with cell culture-adapted virus, which is fully competent for replication in this cell type. We compared the sequences of wild-type EIAV and a full-length infectious proviral clone of the cell culture-adapted EIAV and found that the genomes were relatively well conserved with the exception of the envelope gene region, which showed extensive sequence differences. We therefore constructed several wild-type and cell culture-adapted virus chimeras to examine the role of the envelope gene in replication in different cell types in vitro. Unlike wild-type virus, which is restricted by an early event(s) for replication in equine dermis cells, the wild-type outer envelope gene chimeras are replication competent in this cell type. We conclude that even though there are extensive sequence differences between wild-type and cell culture-adapted viruses in the surface envelope gene region, this domain is not a determinant of the differing in vitro cell tropisms. C1 N CAROLINA STATE UNIV,COLL VET MED,DEPT MICROBIOL PATHOL & PARASITOL,BOX 8401,RALEIGH,NC 27606. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [R01-AI24904, 1K11-AI00963] NR 53 TC 58 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4085 EP 4097 PG 13 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600012 PM 1318398 ER PT J AU SHIRAI, M AKATSUKA, T PENDLETON, CD HOUGHTEN, R WYCHOWSKI, C MIHALIK, K FEINSTONE, S BERZOFSKY, JA AF SHIRAI, M AKATSUKA, T PENDLETON, CD HOUGHTEN, R WYCHOWSKI, C MIHALIK, K FEINSTONE, S BERZOFSKY, JA TI INDUCTION OF CYTOTOXIC T-CELLS TO A CROSS-REACTIVE EPITOPE IN THE HEPATITIS-C VIRUS NONSTRUCTURAL RNA POLYMERASE-LIKE PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; HUMAN IMMUNODEFICIENCY VIRUS; TOXIC LYMPHOCYTES-T; MAJOR HISTOCOMPATIBILITY COMPLEX; RECOMBINANT VACCINIA VIRUS; NON-A-HEPATITIS; SYNTHETIC PEPTIDES; TRANSPLANTATION ANTIGENS; FINE SPECIFICITY; CYTO-TOXICITY AB Cytotoxic T lymphocytes (CTL) have been found to mediate protection in vivo against certain virus infections. CTL also may play an important role in control of infection by hepatitis C virus (HCV), but no CTL epitopes have yet been defined in any HCV protein. The nonstructural protein with homology to RNA polymerase should be a relatively conserved target protein for CTL. To investigate the epitope specificity of CTL specific for this protein, we used 28 peptides from this sequence to study murine CTL. Mice were immunized with a recombinant vaccinia virus expressing the HCV nonstructural region corresponding to the flavivirus NS5 gene (RNA polymerase), and the primed spleen cells were restimulated in vitro with peptides. CTL from H-2d mice responded to a single 16-residue synthetic peptide (HCV 2422 to 2437). This relatively conserved epitope was presented by H-2d class I major histocompatibility complex (MHC) molecules to conventional CD4- CD8+ CTL but was not recognized by CTL restricted by H-2b. Moreover, exon shuffle experiments using several transfectants expressing recombinant D(d)/L(d) and K(d) demonstrated that this peptide is seen in association with alpha-1 and alpha-2 domains of the D(d) class I MHC molecule. This peptide differs from the homologous segments of this nonstructural region from three other HCV isolates by one residue each. Variant peptides with single amino acid substitutions were made to test the effect of each residue on the ability to sensitize targets. Neither substitution affected recognition. Therefore, these conservative mutations affected peptide interaction neither with the D(d) class I MHC molecule nor with the T-cell receptor. Because these CTL cross-react with all four sequenced isolates of HCV in the United States and Japan, if human CTL display similar cross-reactivity, this peptide may be valuable for studies of HCV diagnosis and vaccine development. Our study provides the first evidence that CD8+ CTL can recognize an epitope from the HCV sequence in association with a class I MHC molecule. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. TORREY PINES INST MOLEC STUDIES,SAN DIEGO,CA 92121. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BETHESDA,MD 20014. RI Yang, Chen/G-1379-2010 NR 69 TC 70 Z9 70 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4098 EP 4106 PG 9 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600013 PM 1376366 ER PT J AU BLASCO, R MOSS, B AF BLASCO, R MOSS, B TI ROLE OF CELL-ASSOCIATED ENVELOPED VACCINIA VIRUS IN CELL-TO-CELL SPREAD SO JOURNAL OF VIROLOGY LA English DT Article ID RELEASE; DISSEMINATION; N1-ISONICOTINOYL-N2-3-METHYL-4-CHLOROBENZOYLHYDRAZINE; IDENTIFICATION; HEMAGGLUTININ; CYTOSKELETON; POLYPEPTIDE; INHIBITORS; MEMBRANES; ANTIGEN AB The roles of intracellular naked (INV), cell-associated enveloped (CEV), and extracellular enveloped (EEV) forms of vaccinia virus in cell-to-cell and longer-range spread were investigated by using two closely related strains of vaccinia virus, WR and IHD-J. We confirmed previous results that WR and IHD-J produced similar amounts of INV and formed similar-size primary plaques but that IHD-J produced 10 to 40 times more EEV and spread to distant cells much more efficiently than did WR. Nevertheless, cells infected with WR and IHD-J had similar amounts of CEV, indicating that wrapping and transport of WR virions were unimpaired. A WR mutant with a deletion in VP37, the major outer envelope protein, formed normal amounts of INV; however, the generation of CEV was blocked and plaque formation was inhibited. These results suggested that CEV is the form of virus that mediates cell-to-cell spread. Marker rescue experiments indicated that the differences in EEV production by WR and IHD-J were not due to sequence differences in VP37. The low amount of WR EEV could be attributed to retention of CEV on the cell membrane. In support of this hypothesis, mild treatment with trypsin released as much or more infectious virus from cells infected with WR as it did with cells infected with IHD-J. Most of the virus released by trypsin sedimented with the buoyant density of EEV. Also, addition of trypsin to cells following inoculation with WR led to a comet-shaped distribution of secondary plaques characteristic of IHD-J. These results demonstrated that the release of CEV from the cell surface was limiting for extracellular virus formation and affirmed the role of EEV in long-range spread. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI Blasco, Rafael/B-5829-2016 NR 31 TC 195 Z9 198 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 JUL PY 1992 VL 66 IS 7 BP 4170 EP 4179 PG 10 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600021 PM 1602540 ER PT J AU SEDMAN, SA HUBBERT, NL VASS, WC LOWY, DR SCHILLER, JT AF SEDMAN, SA HUBBERT, NL VASS, WC LOWY, DR SCHILLER, JT TI MUTANT P53 CAN SUBSTITUTE FOR HUMAN PAPILLOMAVIRUS TYPE-16 E6 IN IMMORTALIZATION OF HUMAN KERATINOCYTES BUT DOES NOT HAVE E6-ASSOCIATED TRANSACTIVATION OR TRANSFORMING ACTIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID E2 TRANSCRIPTION UNIT; CARCINOMA CELL-LINES; WILD-TYPE; TUMOR-ANTIGEN; E1A-INDUCIBLE PROMOTER; ESSENTIAL ELEMENT; EARLY GENES; ONCOGENE; MUTATIONS; PROTEIN AB Human papillomavirus type 16 (HPV16) E6 and E7 are selectively retained and expressed in HPV16-associated human genital tumors. E6 is active in several cell culture assays, including transformation of NIH 3T3 cells, trans activation of the adenovirus E2 promoter, and cooperation with E7 to immortalize normal human keratinocytes. Biochemically, the HPV16 E6 protein has been shown to bind to tumor suppressor protein p53 in vitro and induce its degradation in a rabbit reticulocyte lysate. To examine the relationship between the various biological activities of E6 and inactivation of p53, we tested the abilities of dominant negative mutants of p53 to substitute functionally for E6 in the three cell culture assays. While wild-type p53 inhibited keratinocyte proliferation, both mouse and human mutant p53s, in conjunction with E7, increased proliferation of the keratinocytes, resulting in generation of immortalized lines. However, in contrast to E6, mutant p53 was unable to induce transformation or trans activate the adenovirus E2 promoter in NIH 3T3 cells. These results suggest that inactivation of wild-type p53 is necessary for HPV-induced immortalization of human keratinocytes and that different or additional activities are required for E6-dependent transformation and trans activation of NIH 3T3 cells. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [TA-CA-B032] NR 45 TC 85 Z9 86 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4201 EP 4208 PG 8 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600024 PM 1318401 ER PT J AU GORZIGLIA, M KAPIKIAN, AZ AF GORZIGLIA, M KAPIKIAN, AZ TI EXPRESSION OF THE OSU ROTAVIRUS OUTER CAPSID PROTEIN-VP4 BY AN ADENOVIRUS RECOMBINANT SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODIES; BACULOVIRUS RECOMBINANT; CELL LINE; GENE; VIRUS; SPECIFICITIES; INFECTIVITY; VP3; IDENTIFICATION; MECHANISMS AB Full-length cDNA of the VP4 gene of porcine rotavirus strain OSU was cloned into adenovirus type 5 (Ad5) downstream of the E3 promoter. The plaque-purified recombinant (Ad5-OSU VP4) expressed apparently authentic VP4 rotavirus outer capsid protein. The protein had the same molecular size (85 kDa) and electrophoretic mobility as did native OSU VP4 and was immunoprecipitated by a polyclonal antiserum raised to OSU VP4. Cotton rats that possessed prechallenge rotavirus antibodies that may have been acquired either passively or actively developed neutralizing antibodies against the OSU strain following intranasal administration of the live Ad5-OSU VP4 recombinant. The neutralizing activity was enhanced by a parenteral booster injection with baculovirus-expressed OSU VP4 antigen. In addition, a high titer of neutralizing antibodies was induced by parenteral administration of the latter antigen and subsequent intranasal administration of the Ad5-OSU VP4 recombinant. These observations indicate that the VP4 outer capsid protein of a rotavirus strain can be expressed by a recombinant adenovirus vector. This approach warrants further exploration for immunization against rotavirus disease. RP GORZIGLIA, M (reprint author), NIAID,INFECT DIS LAB,EPIDEMIOL SECT,BETHESDA,MD 20892, USA. NR 32 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4407 EP 4412 PG 6 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600049 PM 1318411 ER PT J AU FUJITA, K SILVER, J PEDEN, K AF FUJITA, K SILVER, J PEDEN, K TI CHANGES IN BOTH GP120 AND GP41 CAN ACCOUNT FOR INCREASED GROWTH-POTENTIAL AND EXPANDED HOST RANGE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR-BINDING; MACROPHAGE TROPISM; CD4 RECEPTOR; DNA; HIV-1; MUTATIONS; SEQUENCE; GLYCOPROTEIN; CELLS; CYTOPATHOGENICITY AB Virus derived from an infectious molecular clone of the ELI strain of human immunodeficiency virus type 1 (HIV-1) replicates well in peripheral blood mononuclear cells and in some CD4-positive cell lines but exhibits a delayed time course of infection in CEM and H9 cells and fails to infect SupT1 and U937 cells. If the virus that emerges from infected H9 cells is used to infect CEM and H9 cells, the time course of infection is accelerated and the virus is able to infect U937 and SupT1 cells. In this study, we used the technique of polymerase chain reaction-single-strand conformation polymorphism to localize changes in both the extracellular gp120 and the transmembrane gp41 components of the envelope gene associated with adaptation to growth in tissue culture cell lines. Specifically, mutations were identified both in a region of gp120 implicated in CD4 binding and in the amino-terminal portion of gp41 adjacent to the region involved in fusion. No changes were found in the V3 loop of gp120, a region previously shown to be involved in viral tropism. When these mutations were introduced into the original molecular clone, they conferred an enhanced replicative capacity on ELI. These results demonstrate that two additional determinants in the HIV-1 envelope protein influence viral tropism and growth in vitro. They also may have important implications for the generation of viruses with increased growth potential and expanded host range seen in the late stages of HIV disease. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 43 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4445 EP 4451 PG 7 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600053 PM 1602552 ER PT J AU MIYAZAWA, M NISHIO, J CHESEBRO, B AF MIYAZAWA, M NISHIO, J CHESEBRO, B TI PROTECTION AGAINST FRIEND RETROVIRUS-INDUCED LEUKEMIA BY RECOMBINANT VACCINIA VIRUSES EXPRESSING THE GAG GENE SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; SYNTHETIC PEPTIDES; NEUTRALIZATION EPITOPE; IMMUNE-RESPONSE; CELL CLONES; ERYTHROLEUKEMIA; ANTIBODIES; ANTIGENS; HIV-1 AB High sequence variability in the envelope gene of human immunodeficiency virus has provoked interest in nonenvelope antigens as potential immunogens against retrovirus infection. However, the role of core protein antigens encoded by the gag gene in protective immunity against retroviruses is unclear. By using recombinant vaccinia viruses expressing the Friend murine leukemia helper virus (F-MuLV) gag gene, we could prime CD4+ T-helper cells and protectively immunize susceptible strains of mice against Friend retrovirus infection. Recovery from leukemic splenomegaly developed more slowly after immunization with vaccinia virus-F-MuLV gag than with vaccinia virus-F-MuLV env; however, genetic nonresponders to the envelope protein could be partially protected with Gag vaccines. Class switching of F-MuLV-neutralizing antibodies from immunoglobulin M to immunoglobulin G after challenge with Friend virus complex was facilitated in mice immunized with the Gag antigen. Sequential deletion of the gag gene revealed that the major protective epitope was located on the N-terminal hydrophobic protein p15. C1 NIAID,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 53 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4497 EP 4507 PG 11 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600060 PM 1534853 ER PT J AU PIFAT, DY ENNIS, WH WARD, JM OBERSTE, MS GONDA, MA AF PIFAT, DY ENNIS, WH WARD, JM OBERSTE, MS GONDA, MA TI PERSISTENT INFECTION OF RABBITS WITH BOVINE IMMUNODEFICIENCY-LIKE VIRUS SO JOURNAL OF VIROLOGY LA English DT Note ID BIOLOGICALLY-ACTIVE PROVIRUSES; CELL LEUKEMIA-VIRUS; T-CELL; MOLECULAR-CLONING; HIV-INFECTION; AIDS VIRUS; PATHOGENESIS; MACROPHAGE; GENE; RETROVIRUSES AB Chronic infection of rabbits was induced by a single intraperitoneal injection of bovine immunodeficiency-like virus (BIV-infected cells. Ten BIV-infected animals were monitored serologically for up to 2 years. Results of serologic and virus rescue assays indicated that all animals became infected and demonstrated a rapid and sustained BIV-specific humoral response. BIV was rescued by cocultivation from spleen, lymph nodes, and peripheral blood leukocytes of infected animals. Viral DNA in immune tissues was confirmed by polymerase chain reaction amplification of BIV sequences. These data and specific immunohistochemical staining of mononuclear cells of the spleen for BIV antigen suggest that the infection is targeted to immune system cells. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 42 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4518 EP 4524 PG 7 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600062 PM 1318416 ER PT J AU BOERI, E GIRI, A LILLO, F FERRARI, G VARNIER, OE FERRO, A SABBATANI, S SAXINGER, WC FRANCHINI, G AF BOERI, E GIRI, A LILLO, F FERRARI, G VARNIER, OE FERRO, A SABBATANI, S SAXINGER, WC FRANCHINI, G TI INVIVO GENETIC-VARIABILITY OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 V3-REGION SO JOURNAL OF VIROLOGY LA English DT Note ID GENOME ORGANIZATION; PROVIRAL CLONE; HIV-2; SEQUENCE; ANTIBODIES; INFECTION; ISOLATE; AIDS; NEUTRALIZATION; RETROVIRUS AB The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cysteines of the V3 regions, but its functional similarity with the HIV-1 principal neutralizing epitope is uncertain. We studied the degree of genetic variation of the HIV-2 V3 region in fresh blood samples from 12 HIV-2-seropositive individuals from Guinea-Bissau. Polymerase chain reaction was used to amplify viral fragments of 465 bp containing the V3 region from cellular DNA. Nucleotide sequence analysis of the entire envelope fragment from each patient revealed that the degree of variation among field isolates of HIV-2 is comparable to that observed in the analogous region of HIV-1. Most of the HIV-2 isolates studied were highly related, suggesting the existence of a limited number of different viral strains in the cohort studied. Thus, the HIV-2 and HIV-1 V3 regions vary to a similar degree and may also have analogous functions. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. MAGGIORE HOSP,INFECT DIS CLIN,BOLOGNA,ITALY. HOSP SIMAO MENDEZ,BLOOD BANK,BISSAU,GUINEA BISSAU. INST MICROBIOL,HUMAN RETROVIROL LAB,GENOA,ITALY. RI Ferrari, Guido/A-6088-2015 NR 41 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4546 EP 4550 PG 5 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600067 PM 1602560 ER PT J AU ALONSO, A DERSE, D PETERLIN, BM AF ALONSO, A DERSE, D PETERLIN, BM TI HUMAN CHROMOSOME-12 IS REQUIRED FOR OPTIMAL INTERACTIONS BETWEEN TAT AND TAR OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN RODENT CELLS SO JOURNAL OF VIROLOGY LA English DT Note ID LONG TERMINAL REPEAT; TRANS-ACTIVATION; HIV-1 TAT; TRANSCRIPTIONAL REGULATION; MUTATIONAL ANALYSIS; MESSENGER-RNA; FUNCTIONAL DOMAINS; GENE-EXPRESSION; LOOP SEQUENCE; HUMAN HYBRIDS AB Levels of trans activation of the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) by the virally encoded transactivator Tat show marked species-specific differences. For example, levels of transactivation observed in Chinese hamster ovary (CHO) rodent cells are 10-fold lower than those in human cells or in CHO cells that contain the human chromosome 12. Thus, the human chromosome 12 codes for a protein or proteins that are required for optima Tat activity. Here, the function of these cellular proteins was analyzed by using a number of modified HIV-1 LTRs and Tats. Neither DNA-binding proteins that bind to the HIV-1 LTR nor proteins that interact with the activation domain of Tat could be implicated in this defect. However, since species-specific differences were no longer observed with hybrid proteins that contain the activation domain of Tat fused to heterologous RNA-binding proteins, optimal interactions between Tat and the trans-acting responsive RNA (TAR) must depend on this factor(s). C1 UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. NR 59 TC 82 Z9 82 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1992 VL 66 IS 7 BP 4617 EP 4621 PG 5 WC Virology SC Virology GA HY086 UT WOS:A1992HY08600080 PM 1602563 ER PT J AU CHERRYPEPPERS, G SORKIN, J ANDRES, R BAUM, BJ SHIP, JA AF CHERRYPEPPERS, G SORKIN, J ANDRES, R BAUM, BJ SHIP, JA TI SALIVARY-GLAND FUNCTION AND GLUCOSE METABOLIC STATUS SO JOURNALS OF GERONTOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; DIFFERENT AGE-GROUPS; FLOW-RATE; AUTONOMIC NEUROPATHY; XEROSTOMIA; SECRETION; THIRST AB To study the relationship between glucose metabolic status and salivary gland function in different-aged persons, subjects with diabetes mellitus (DM = 11), impaired glucose tolerance (IGT = 26), and controls (n = 26), aged 24 to 93, were examined in the oral physiology component of the Baltimore Longitudinal Study of Aging. All were generally healthy (except DM) and nonmedicated. The controls and subjects with IGT were classified using World Health Organization criteria, and diabetic status was assessed using Hb1Ac levels. Unstimulated and 2% citrate-stimulated parotid and submandibular salivary flow rates were collected, and subjective responses to questions about salivary hypofunction were evaluated. No statistically significant differences were observed between the three groups, nor between young and old subjects with altered glucose metabolism. These findings suggest that among well-controlled individuals with altered glucose metabolism, salivary gland function is not significantly impaired. C1 NIA,METAB SECT,CLIN PHYSIOL LAB,BETHESDA,MD 20892. RP CHERRYPEPPERS, G (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 48 TC 22 Z9 22 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1992 VL 47 IS 4 BP M130 EP M134 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JC386 UT WOS:A1992JC38600013 PM 1624696 ER PT J AU GREENBERGER, JS SAKAKEENY, MA LEIF, J ANKLESARIA, P PIERCE, JH SHADDUCK, RK AF GREENBERGER, JS SAKAKEENY, MA LEIF, J ANKLESARIA, P PIERCE, JH SHADDUCK, RK TI EXPRESSION OF M-CSF AND ITS RECEPTOR (C-FMS) DURING FACTOR-INDEPENDENT CELL-LINE EVOLUTION FROM HEMATOPOIETIC PROGENITOR CELLS COCULTIVATED WITH GAMMA-IRRADIATED MARROW STROMAL CELL-LINES SO LEUKEMIA LA English DT Article ID COLONY-STIMULATING FACTOR; REVERSIBLE MONOCYTIC DIFFERENTIATION; PROTEIN KINASE-C; GROWTH-FACTOR; MALIGNANT TRANSFORMATION; AUTOCRINE SECRETION; PHORBOL ESTERS; MYELOID CELLS; X-IRRADIATION; FACTOR GENES AB Gamma irradiation of plateau-phase clonal bone marrow stromal cell lines produces factor-independent growth of cocultivated clonal interleukin-3/granulocyte-macrophage colony-stimulating factor-dependent hematopoietic progenitor cell lines. The process is associated with three biologic changes including: (i) adherence of hematopoietic cells to stromal cells forming 'cobblestone islands'; (ii) an intermediate stage [during which the cells show proliferation in suspension in the presence in leukemogenic stromal factor (LSF), a factor similar to macrophage colony-stimulating factor (M-CSF) released by irradiated stromal cells, and transient hematopoietic cell surface expression of MAC-1, and c-fms (M-CSF receptor)]; and (iii) a third stage of factor-independence. A monoclonal antibody to M-CSF receptor inhibited proliferation of intermediate stage but not all factor-independent cell subclones. In the present studies, a subclonal factor-independent malignant subline of FDC-P1JL26 derived by cocultivation with gamma-irradiated stromal cells as wall as the parent clone and intermediate stage cells were shown to express significant levels of M-CSF polyA+ mRNA and M-CSF of at least two sizes (23 and 16 kDa) as detected by S-35-methionine labelling and immunoprecipitation with polyclonal anti-M-CSF antiserum. There was no significant difference in intracellular M-CSF protein size between cells at each of the three stages of biologic change. This M-CSF was not detected on the cell surface by fluorescence-activated cell sorting (FACS). In contrast, c-fms expression at the cell surface was detected by FACS analysis and c-fms polyA+ mRNA was only detected during the intermediate stage of induction of factor-independence. FDC-P1JL26 parent cells, the subclone stimulated by LSF, and the factor-independent subclone, showed little or no detectable autophosphorylation of the c-fms receptor at tyrosine. There was no detectable rearrangement of the M-CSF or c-fms genes by Southern analysis between clonal lines during the three stages. While we cannot rule out an autocrine mechanism or mutated c-fms receptor mechanism, the data also suggest that evolution of hemopoietic cell factor-independence during cocultivation with irradiated stromal cells may involve a mechanism distal to the c-fms receptor/M-CSF interaction. C1 NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. WESTERN PENN HOSP,PITTSBURGH,PA 15224. RP GREENBERGER, JS (reprint author), UNIV MASSACHUSETTS,MED CTR,DEPT RADIAT ONCOL,55 LAKE AVE N,WORCESTER,MA 01655, USA. FU NCI NIH HHS [CA 15237, CA 39851]; NIDCR NIH HHS [DE 08798] NR 34 TC 10 Z9 10 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 1992 VL 6 IS 7 BP 626 EP 633 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA JE496 UT WOS:A1992JE49600004 PM 1385639 ER PT J AU MOONEN, CTW LIU, GY VANGELDEREN, P SOBERING, G AF MOONEN, CTW LIU, GY VANGELDEREN, P SOBERING, G TI A FAST GRADIENT-RECALLED MRI TECHNIQUE WITH INCREASED SENSITIVITY TO DYNAMIC SUSCEPTIBILITY EFFECTS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Letter ID CONTRAST; BRAIN RP MOONEN, CTW (reprint author), NIH,INVIVO NMR RES CTR,BEIP,NCRR,BLDG 10,ROOM BID123,BETHESDA,MD 20892, USA. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 13 TC 81 Z9 81 U1 0 U2 3 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 JUL PY 1992 VL 26 IS 1 BP 184 EP 189 DI 10.1002/mrm.1910260118 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JB377 UT WOS:A1992JB37700017 PM 1625564 ER PT J AU ATKINSON, TP KALINER, MA AF ATKINSON, TP KALINER, MA TI ANAPHYLAXIS SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID EXERCISE-INDUCED ANAPHYLAXIS; INSECT HYPERSENSITIVITY; IDIOPATHIC ANAPHYLAXIS; RECURRENT ANAPHYLAXIS; PENICILLIN ALLERGY; RUBBER; IMMUNOTHERAPY; SENSITIVITY; DRUGS; RISK RP ATKINSON, TP (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 47 TC 29 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 1992 VL 76 IS 4 BP 841 EP 855 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA JB112 UT WOS:A1992JB11200004 PM 1614236 ER PT J AU MORGAN, MJ KIMES, AS LONDON, ED AF MORGAN, MJ KIMES, AS LONDON, ED TI POSSIBLE ROLES FOR NITRIC-OXIDE IN AIDS AND ASSOCIATED PATHOLOGY SO MEDICAL HYPOTHESES LA English DT Article ID HOMOSEXUAL MEN; KAPOSIS SARCOMA; QUINOLINIC ACID; NERVOUS-SYSTEM; AMYL NITRITE; RAT; NEUROTOXICITY AB The endogenous free radical, nitric oxide (NO), plays a neurotransmitter-like role in vascular endothelium, a second messenger role in N-methyl-D-aspartate (NMDA)-responsive neurons in the central nervous system (CNS), a neurotoxic role after its release from these neurons, and a cytotoxic role after its release by macrophages. NO also derives from exogenous sources, such as the nitrite inhalants, amyl, butyl and isobutyl nitrite. There is evidence that abuse of nitrite inhalants can affect immunomodulation, and epidemiological studies suggest that such abuse may be a cofactor in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Hitherto, however, the potential role of NO in such pathogenesis has not been examined. This paper presents some current evidence that implicates both endogenous and exogenous sources of NO in AIDS and associated pathology. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 38 TC 18 Z9 18 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUL PY 1992 VL 38 IS 3 BP 189 EP 193 DI 10.1016/0306-9877(92)90092-Q PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JB943 UT WOS:A1992JB94300003 PM 1513271 ER PT J AU ABASSI, Z GOLOMB, E KEISER, HR AF ABASSI, Z GOLOMB, E KEISER, HR TI NEUTRAL ENDOPEPTIDASE INHIBITION INCREASES THE URINARY-EXCRETION AND PLASMA-LEVELS OF ENDOTHELIN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID RESPONSES; PEPTIDE RP ABASSI, Z (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 10 TC 42 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 1992 VL 41 IS 7 BP 683 EP 685 DI 10.1016/0026-0495(92)90303-R PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JB355 UT WOS:A1992JB35500001 PM 1535677 ER PT J AU COON, PJ ROGUS, EM GOLDBERG, AP AF COON, PJ ROGUS, EM GOLDBERG, AP TI TIME COURSE OF PLASMA-FREE FATTY-ACID CONCENTRATION IN RESPONSE TO INSULIN - EFFECT OF OBESITY AND PHYSICAL-FITNESS SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CLAMP TECHNIQUE; GLUCOSE; RESISTANCE; SENSITIVITY; MECHANISMS C1 FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,METAB SECT,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. FU NCRR NIH HHS [MO1 RR02719]; NIA NIH HHS [KO8 AG00347, P01 AG04402-05] NR 26 TC 24 Z9 24 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 1992 VL 41 IS 7 BP 711 EP 716 DI 10.1016/0026-0495(92)90309-X PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JB355 UT WOS:A1992JB35500007 PM 1619988 ER PT J AU MAGUIRE, JE FRELS, WI RICHARDSON, JC WEISSMAN, JD SINGER, DS AF MAGUIRE, JE FRELS, WI RICHARDSON, JC WEISSMAN, JD SINGER, DS TI INVIVO FUNCTION OF REGULATORY DNA-SEQUENCE ELEMENTS OF A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHLORAMPHENICOL ACETYLTRANSFERASE; INTERFERON TREATMENT; TRANSGENIC MICE; MAMMALIAN-CELLS; EXPRESSION; ANTIGENS; ENHANCER; PROMOTER; REGION; GAMMA AB Major histocompatibility complex class I genes are expressed in nearly all somatic tissues, although their level of expression varies. By analysis of a set of promoter deletion mutants introduced into transgenic mice, a complex regulatory element, consisting of overlapping enhancer and silencer activities, is demonstrated to function as a tissue-specific regulator of class I expression. The enhancer activity predominates in lymphoid tissues but not in nonlymphoid tissues. In contrast to the tissue-specific function of the complex regulatory element, a second novel silencer element is shown to function in both lymphoid and nonlymphoid tissues. The complement of DNA-binding factors in different cell lines is shown to correlate with the levels of class I expression. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. NR 27 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1992 VL 12 IS 7 BP 3078 EP 3086 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JA250 UT WOS:A1992JA25000020 PM 1620117 ER PT J AU BARRETT, J BIRRER, MJ KATO, GJ DOSAKAAKITA, H DANG, CV AF BARRETT, J BIRRER, MJ KATO, GJ DOSAKAAKITA, H DANG, CV TI ACTIVATION DOMAINS OF L-MYC AND C-MYC DETERMINE THEIR TRANSFORMING POTENCIES IN RAT EMBRYO CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING PROTEINS; LEUCINE ZIPPER; GENE; EXPRESSION; SEQUENCE; DIFFERENTIATION; TRANSCRIPTION; FIBROBLASTS; ONCOGENES; REGIONS AB Members of the Myc family of proteins share a number of protein motifs that are found in regulators of gene transcription. Conserved stretches of amino acids found in the N-terminal transcriptional activation domain of c-Myc are required for cotransforming activity. Most of the Myc proteins contain the basic helix-loop-helix zipper (bHLH-Zip) DNA-binding motif which is also required for the cotransforming activity of c-Myc. L-Myc, the product of a myc family gene that is highly amplified in many human lung carcinomas, was found to cotransform primary rat embryo cells with an activated ras gene. However, L-Myc cotransforming activity was only 1 to 10% of that of c-Myc (M. J. Birrer, S. Segal, J. S. DeGreve, F. Kaye, E. A. Sausville, and J. D. Minna, Mol. Cell. Biol. 8:2668-2673, 1988). We sought to determine whether functional differences between c-Myc and L-Myc in either the N-terminal or the C-terminal domain could account for the relatively diminished L-Myc cotransforming activity. Although the N-terminal domain of L-Myc could activate transcription when fused to the yeast GAL4 DNA-binding domain, the activity was only 5% of that of a comparable c-Myc domain. We next determined that the interaction of the C-terminal bHLH-Zip region of L-Myc or c-Myc with that of a Myc partner protein, Max, was equivalent in transfected cells. A Max expression vector was found to augment the cotransforming activity of L-Myc as well as that of c-Myc. In addition, a bacterially synthesized DNA-binding domain of L-Myc, like that of c-Myc, heterodimerizes with purified Max protein to bind the core DNA sequence CACGTG. To determine the region of L-Myc responsible for its relatively diminished cotransforming activity, we constructed chimeras containing exons 2 (constituting activation domains) and 3 (constituting DNA-binding domains) of c-Myc fused to those of L-Myc. The cotransforming potencies of these chimeras were compared with those of full-length L-Myc or c-Myc in rat embryo cells. The relative cotransforming activities suggest that the potencies of the activation domains determine the cotransforming efficiencies for c-Myc and L-Myc. This correlation supports the hypothesis that the Myc proteins function in neoplastic cotransformation as transcription factors. C1 JOHNS HOPKINS UNIV,SCH MED,DIV HEMATOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. NCI,BIOMARKERS & PREVENT RES BRANCH,KENSINGTON,MD 20895. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU NCI NIH HHS [CA51497, K11CA01622] NR 52 TC 52 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1992 VL 12 IS 7 BP 3130 EP 3137 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JA250 UT WOS:A1992JA25000025 PM 1620120 ER PT J AU KANG, SM TSANG, W DOLL, S SCHERLE, P KO, HS TRAN, AC LENARDO, MJ STAUDT, LM AF KANG, SM TSANG, W DOLL, S SCHERLE, P KO, HS TRAN, AC LENARDO, MJ STAUDT, LM TI INDUCTION OF THE POU DOMAIN TRANSCRIPTION FACTOR OCT-2 DURING T-CELL ACTIVATION BY COGNATE ANTIGEN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN INTERLEUKIN-2 GENE; BINDING-PROTEIN; EXPRESSION; RECEPTOR; ENHANCER; REGION; IDENTIFICATION; PROLIFERATION; LYMPHOCYTES; ELEMENTS AB Oct-2 is a transcription factor that binds specifically to octamer DNA motifs in the promoters of immunoglobulin and interleukin-2 genes. All tumor cell lines from the B-cell lineage and a few from the T-cell lineage express Oct-2. To address the role of Oct-2 in the T-cell lineage, we studied the expression of Oct-2 mRNA and protein in nontransformed human and mouse T cells. Oct-2 was found in CD4+ and CD8+ T cells prepared from human peripheral blood and in mouse lymph node T cells. In a T-cell clone specific for pigeon cytochrome c in the context of I-E(k), Oct-2 was induced by antigen stimulation, with the increase in Oct-2 protein seen first at 3 h after activation and continuing for at least 24 h. Oct-2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A, as well as by protein synthesis inhibitors. These results suggest that Oct-2 participates in transcriptional regulation during T-cell activation. The relatively delayed kinetics of Oct-2 induction suggests that Oct-2 mediates the changes in gene expression which occur many hours or days following antigen stimulation of T lymphocytes. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. NR 33 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1992 VL 12 IS 7 BP 3149 EP 3154 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JA250 UT WOS:A1992JA25000027 PM 1620122 ER PT J AU RESNICK, MA ZGAGA, Z HIETER, P WESTMORELAND, J FOGEL, S NILSSONTILLGREN, T AF RESNICK, MA ZGAGA, Z HIETER, P WESTMORELAND, J FOGEL, S NILSSONTILLGREN, T TI RECOMBINATIONAL REPAIR OF DIVERGED DNAS - A STUDY OF HOMOEOLOGOUS CHROMOSOMES AND MAMMALIAN YACS IN YEAST SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE RECOMBINATIONAL REPAIR; DOUBLE-STRAND BREAKS; YACS; DIVERGENT DNA; MISMATCH REPAIR ID DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; MISMATCH-REPAIR; GENE CONVERSION; NUCLEOTIDE-SEQUENCE; ARTIFICIAL CHROMOSOMES; S-CEREVISIAE; HIS4 REGION; CARLSBERGENSIS; MUTANTS AB Recombinational repair is the means by which DNA double-strand breaks (DSBs) are repaired in yeast. DNA divergence between chromosomes was shown previously to inhibit repair in diploid G1 cells, resulting in chromosome loss at low nonlethal doses of ionizing radiation. Furthermore, 15-20% divergence prevents meiotic recombination between individual pairs of Saccharomyces cerevisiae and S. carlsbergensis chromosomes in an otherwise S. cerevisiae background. Based on analysis of the efficiency of DSB-induced chromosome loss and direct genetic detection of intragenic recombination, we conclude that limited DSB recombinational repair can occur between homoeologous chromosomes. There is no difference in loss between a repair-proficient Pms+ strain and a mismatch repair mutant, pms1. Since DSB recombinational repair is tolerant of diverged DNAs, this type of repair could lead to novel genes and altered chromosomes. The sensitivity to DSB-induced loss of 11 individual yeast artificial chromosomes (YACs) containing mouse or human (chromosome 21 or HeLa) DNA was determined. Recombinational repair between a pair of homologous HeLa YACs appears as efficient as that between homologous yeast chromosomes in that there is no loss at low radiation doses. Single YACs exhibited considerable variation in response, although the response for individual YACs was highly reproducible. Based on the results with the yeast homoeologous chromosomes, we propose that the potential exists for intra- YAC recombinational repair between diverged repeat DNA and that the extent of repair is dependent upon the amount of repeat DNA and the degree of divergence. The sensitivity of YACs containing mammalian DNA to ionizing radiation-induced loss may thus be an indicator of the extent of repeat DNA. C1 UNIV ZAGREB, BIOL & MICROBIAL GENET, YU-41000 ZAGREB, YUGOSLAVIA. JOHNS HOPKINS UNIV, SCH MED, DEPT MOLEC BIOL & GENET, BALTIMORE, MD 21205 USA. UNIV CALIF BERKELEY, DEPT PLANT BIOL, BERKELEY, CA 94720 USA. UNIV COPENHAGEN, INST GENET, DK-1353 COPENHAGEN, DENMARK. RP NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. FU NCI NIH HHS [5PO1CA16519] NR 47 TC 34 Z9 34 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JUL PY 1992 VL 234 IS 1 BP 65 EP 73 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JF256 UT WOS:A1992JF25600008 PM 1495486 ER PT J AU STEPHENS, JC GILBERT, DA YUHKI, N OBRIEN, SJ AF STEPHENS, JC GILBERT, DA YUHKI, N OBRIEN, SJ TI ESTIMATION OF HETEROZYGOSITY FOR SINGLE-PROBE MULTILOCUS DNA FINGERPRINTS SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE HYPERVARIABLE MINISATELLITES; GENETIC RELATEDNESS; POLYMORPHISM; GENE DIVERSITY; POPULATION GENETICS ID HIGHLY VARIABLE MINISATELLITES; VNTR MARKERS; POPULATION; PATERNITY; DIVERSITY; STRAINS AB In spite of the increasing application of DNA fingerprinting to natural populations and to the genetic identification of humans, explicit methods for estimation of basic population genetic parameters from DNA fingerprinting data have not been developed. Contributing to this omission is the inability to determine, for multilocus fingerprinting probes, relatively important genetic information, such as the number of loci, the number of alleles, and the distribution of these alleles into specific loci. One of the most useful genetic parameters that could be derived from such data would be the average heterozygosity, which has traditionally been employed to measure the level of genetic variation within populations and to compare genetic variation among different loci. We derive here explicit formulas for both the estimation of average heterozygosity at multiple hypervariable loci and a maximum value for this estimate. These estimates are based upon the DNA restriction-pattern matrices that are typical for fingerprinting studies of humans and natural populations. For several empirical data sets from our laboratory, estimates of average and maximal heterozygosity are shown to be relatively close to each other. Furthermore, variances of these statistics based on simulation studies are relatively small. These observations, as well as consideration of the effect of missing alleles and alternate numbers of loci, suggest that the average heterozygosity can be accurately estimated using phenotypic DNA fingerprint patterns, because this parameter is relatively insensitive to the lack of certain genetic information. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP STEPHENS, JC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 30 TC 113 Z9 120 U1 1 U2 1 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUL PY 1992 VL 9 IS 4 BP 729 EP 743 PG 15 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA JB378 UT WOS:A1992JB37800013 PM 1630309 ER PT J AU SIMONS, SS OSHIMA, H SZAPARY, D AF SIMONS, SS OSHIMA, H SZAPARY, D TI HIGHER LEVELS OF CONTROL - MODULATION OF STEROID HORMONE-REGULATED GENE-TRANSCRIPTION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GLUCOCORTICOID RECEPTOR-BINDING; BREAST CANCER-CELLS; ALPHA-FETOPROTEIN GENE; RAT HEPATOMA-CELLS; CALF THYMUS DNA; ESTROGEN-RECEPTOR; RESPONSE ELEMENT; TYROSINE AMINOTRANSFERASE; PROGESTERONE-RECEPTOR; AGONIST ACTIVITY RP SIMONS, SS (reprint author), NIDDKD, STEROID HORMONES SECT, BLDG 8, ROOM B2A-07, BETHESDA, MD 20892 USA. NR 100 TC 70 Z9 69 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1992 VL 6 IS 7 BP 995 EP 1002 DI 10.1210/me.6.7.995 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JF421 UT WOS:A1992JF42100001 PM 1324423 ER PT J AU PINCUS, SH CARMACK, CE AF PINCUS, SH CARMACK, CE TI VARIABLE REGIONS OF ANTIBODIES TO SYNTHETIC POLYPEPTIDES .3. ANTIBODIES ARISING IN RESPONSE TO ADMINISTRATION OF ANTIIDIOTOPE SO MOLECULAR IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSE; IDIOTYPIC NETWORKS; GENES; IMMUNIZATION; DNA; MANIPULATION; SPECIFICITY; (T,G)-A-L AB Antibodies elicited by the synthetic polypeptide antigen (T,G)-A-L are directed against two distinct epitopes. The majority of antibodies bind to a GT containing epitope and bear an idiotope defined by monoclonal antibodies 17 and 19. In this study, we have examined the effect of in vivo administration of the 17 and 19 antibodies to mice. Administration of anti-idiotope elicits anti-(T,G)-A-L antibodies in all strains of mice tested, including genetic non-responders to (T,G)-A-L. These antibodies bind to GT and express the idiotope. Additionally, idiotope expressing antibodies that fail to bind to antigen are also produced. Monoclonal anti-(anti-idiotope) antibodies were made. One antibody bound to (T,G)-A-L, the other did not. Sequence analysis was performed and the V-regions of (T,G)-A-L binding antibodies were compared to those of the antibody that failed to bind antigen. Both sets of antibodies are derived from the same germline V-genes as the anti-(T,G)-A-L antibodies. These results have implications for understanding the nature of network regulation of the immune system and for those attempting idiotypic vaccination. C1 MED BIOL INST,LA JOLLA,CA 92037. RP PINCUS, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 26 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL-AUG PY 1992 VL 29 IS 7-8 BP 811 EP 819 DI 10.1016/0161-5890(92)90118-H PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA JD342 UT WOS:A1992JD34200001 PM 1378927 ER PT J AU SAUNERONAVA, L COE, JE MOLD, C DUCLOS, TW AF SAUNERONAVA, L COE, JE MOLD, C DUCLOS, TW TI HAMSTER FEMALE PROTEIN-BINDING TO CHROMATIN, HISTONES AND DNA SO MOLECULAR IMMUNOLOGY LA English DT Article ID C-REACTIVE PROTEIN; AMYLOID-P-COMPONENT; ACUTE-PHASE REACTANT; SYRIAN-HAMSTER; MYELOMA PROTEIN; SERUM; PENTRAXIN; CALCIUM; MOUSE; PHOSPHOCHOLINE AB Hamster female protein (FP) is a member of the family of proteins known as pentraxins which share amino acid sequence homology, cyclic pentameric structure and calcium-dependent binding to ligands. Other members of this family include C-reactive protein (CRP) and serum amyloid P component (SAP), and most species synthesize both CRP and SAP. FP is unusual in that it is apparently the only pentraxin produced in hamsters, it is under hormonal control and it shares binding characteristics with both CRP and SAP. CRP has been defined and isolated by its calcium-dependent binding to pneumococcal C-polysaccharide via phosphocholine (PC) residues. SAP has been isolated by calcium-dependent binding to agarose. FP binds to both PC and agarose. Recently, both SAP and CRP have been found to bind to chromatin in a calcium-dependent manner and involvement of these proteins in the clearance of nuclear material has been proposed. In this paper we test whether FP shares the ability to bind to chromatin and histones, and compare its relative avidities for these ligands. Similar to CRP, FP bound to histones H1 and H2A, and chromatin. FP shared with SAP the ability to bind to DNA. However, FP binding was inhibited by PC for all ligands, whereas SAP binding was not. FP and SAP also failed to compete with each other for binding to DNA. By cross-inhibition FP bound much less well to PC than CRP, but was a very effective inhibitor of CRP binding to H2A. These studies demonstrate that chromatin and histone binding are conserved among these pentraxins. The role of the proposed PC binding site in these binding reactions is discussed. C1 VET ADM MED CTR,2100 RIDGECREST DR SE,ALBUQUERQUE,NM 87108. UNIV NEW MEXICO,SCH MED,DEPT MED,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT MICROBIOL,ALBUQUERQUE,NM 87131. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [AI28358] NR 44 TC 4 Z9 4 U1 0 U2 1 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 JUL-AUG PY 1992 VL 29 IS 7-8 BP 837 EP 845 DI 10.1016/0161-5890(92)90121-D PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA JD342 UT WOS:A1992JD34200004 PM 1378928 ER PT J AU BELLAND, RJ CHEN, T SWANSON, J FISCHER, SH AF BELLAND, RJ CHEN, T SWANSON, J FISCHER, SH TI HUMAN NEUTROPHIL RESPONSE TO RECOMBINANT NEISSERIAL OPA PROTEINS SO MOLECULAR MICROBIOLOGY LA English DT Article ID GONOCOCCUS INFECTION; ESCHERICHIA-COLI; HELA-CELLS; GONORRHOEAE; OPACITY; EXPRESSION; ATTACHMENT; LEUKOCYTES; VARIANTS AB Interactions of human neutrophils with recombinant Escherichia coli expressing gonococcal outer membrane Opa proteins were examined using chemiluminescent and biological assays. Seven opa loci from Neisseria gonorrhoeae MS11 4.8 were expressed as beta-lactamase-Opa fusion proteins that contained all but the mature N-terminal amino acid of the full-length Opa protein fused to three N-terminal amino acids derived from the mature beta-lactamase. The Opa fusion proteins were exported and assembled in the outer membrane of E. coli in a manner similar to that of Opa in N. gonorrhoeae, as evaluated by antibody binding and in situ proteolytic cleavage. All fusion proteins exhibited the characteristic heat-modifiable migration in SDS-polyacrylamide gel electrophoresis that typifies Opa proteins of neisseriae. Opa fusion proteins conferred on E. coli the ability to stimulate a chemiluminescent response from human neutrophils in the absence of antibody or complement. The nature of the response in terms of chemiluminescence, phagocytosis, and killing was in all cases analogous to that seen using N. gonorrhoeae expressing the equivalent Opa protein. Neither E. coli nor gonococci expressing OpaA elicited a response from neutrophils. Use of E. coli expressing Opa fusions should be useful in defining their biological activities and pathogenic roles. RP BELLAND, RJ (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 32 TC 54 Z9 54 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 1992 VL 6 IS 13 BP 1729 EP 1737 DI 10.1111/j.1365-2958.1992.tb01345.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA JC204 UT WOS:A1992JC20400002 PM 1630313 ER PT J AU OGINO, Y FRASER, CM COSTA, T AF OGINO, Y FRASER, CM COSTA, T TI SELECTIVE INTERACTION OF BETA-2-ADRENERGIC AND ALPHA-2-ADRENERGIC RECEPTORS WITH STIMULATORY AND INHIBITORY GUANINE NUCLEOTIDE-BINDING PROTEINS SO MOLECULAR PHARMACOLOGY LA English DT Note ID CATALYZED ADP-RIBOSYLATION; CHOLERA-TOXIN; ADENYLATE-CYCLASE; REGULATORY COMPONENT; PHOSPHOLIPASE-C; ACTIVATION; MEMBRANES; CELLS; SITE; TRANSDUCIN AB In Chinese hamster ovary cells expressing recombinant beta(2)-adrenergic receptors, isoproterenol enhanced cholera toxin-catalyzed ADP-ribosylation of the large form of G(s-alpha). The effect was stereoselectively blocked by the enantiomers of propranolol, indicating receptor mediation. The ADP-ribosylated form of G(s) alpha-subunit was resolved into a triplet in gradient gels. Beta(2)-Adrenergic receptors increased both the labeling and the apparent mass of the slower migrating forms of large G(s-alpha), as determined by autoradiography and immunoblotting, suggesting that G(s-alpha) can incorporate more than one ADP-ribose per molecule. In cells coexpressing similar amounts of beta(2)-adrenergic, alpha(2)-adrenergic, and m1 muscarinic receptors, beta(2) receptors stimulated the ADP-ribosylation of only large G(s) and alpha(2) receptors that of only G(i); muscarinic receptors had no apparent effect. Thus, in native membranes there appears to be a selectivity for the interaction between adrenergic receptor subtypes and G(s-alpha) or G(i-alpha) subunits. C1 NIAAA,NEUROGENET LAB,MOLEC NEUROBIOL SECT,12501 WASHINGTON AVE,ROCKVILLE,MD 20852. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 28 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1992 VL 42 IS 1 BP 6 EP 9 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JE032 UT WOS:A1992JE03200002 PM 1321955 ER PT J AU RUSSELL, LB HUNSICKER, PR SHELBY, MD AF RUSSELL, LB HUNSICKER, PR SHELBY, MD TI MELPHALAN, A 2ND CHEMICAL FOR WHICH SPECIFIC-LOCUS MUTATION-INDUCTION IN THE MOUSE IS MAXIMUM IN EARLY SPERMATIDS SO MUTATION RESEARCH LA English DT Article DE CHLORAMBUCIL; GERM-CELL STAGES; SPERMATOGONIAL STEM CELLS; MELPHALAN ID CELLS AB Melphalan (MLP), a bifunctional alkylating agent structurally related to the highly mutagenic chemical chlorambucil (CHL), was found to induce high frequencies of specific-locus mutations in postspermatogonial germ cells of the mouse, and to be one of only a few chemicals that is also mutagenic in spermatogonial stem cells. Productivity patterns following MLP exposures resembled those that had been found for CHL. Mutation rates in successive male germ-cell stages were measured at three MLP-exposure levels in a total of 95 375 offspring. While the induced (experimental minus historical-control) mutation rate is relatively low in stem-cell spermatogonia (1.2 x 10(-5) per locus at a weighted-mean exposure of 7.3 mg/kg), it is about 5 times higher in poststem-cell stages overall, and peaks at 26.7 x 10(-5) per locus in early spermatids at a weighted-mean exposure of only 5.7 mg/kg. This "type-2 pattern" of mutation yield (Russell et al., 1990), i.e., peak sensitivity in early spermatids, has heretofore been found for only one other chemical, CHL. Mutation-rate data earlier reported for CHL (Russell et al., 1989) were augmented in the present study for comparison with MLP-induced rates. Because of the greater toxicity of MLP, average exposures used for this chemical were only about one-half of those for CHL. When MLP and CHL mutation rates are extrapolated to equimolar doses, they appear very similar for poststem-cell stages overall. However, in the case of CHL, a somewhat higher proportion of the mutations is induced in early spermatids than in the case of MLP. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP RUSSELL, LB (reprint author), OAK RIDGE NATL LAB,DIV BIOL,POB 2009,OAK RIDGE,TN 37831, USA. FU NIEHS NIH HHS [22Y01-ES-10067] NR 10 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1992 VL 282 IS 3 BP 151 EP 158 DI 10.1016/0165-7992(92)90089-Z PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JD345 UT WOS:A1992JD34500004 PM 1378547 ER PT J AU KLIGERMAN, AD ALLEN, JW BRYANT, MF CAMPBELL, JA COLLINS, BW DOERR, CL EREXSON, GL KWANYUEN, P MORGAN, DL AF KLIGERMAN, AD ALLEN, JW BRYANT, MF CAMPBELL, JA COLLINS, BW DOERR, CL EREXSON, GL KWANYUEN, P MORGAN, DL TI CYTOGENETIC STUDIES OF MICE EXPOSED TO STYRENE BY INHALATION SO MUTATION RESEARCH LA English DT Article DE STYRENE; CHROMOSOME ABERRATIONS; SISTER-CHROMATID EXCHANGE; MICRONUCLEI; MICE; INHALATION ID PERIPHERAL-BLOOD LYMPHOCYTES; SISTER CHROMATID EXCHANGE; CHROMOSOMAL-ABERRATIONS AB The data for the in vivo genotoxicity of styrene (STY) are equivocal. To evaluate the clastogenicity and sister-chromatid exchange (SCE)-inducing potential of STY in vivo under carefully controlled conditions, B6C3F1 female mice were exposed by inhalation for 6 h/day for 14 consecutive days to either 0, 125, 250 or 500 ppm STY. One day after the final exposure, peripheral blood, spleen, and lungs were removed and cells were cultured for the analysis of micronucleus (MN) induction using the cytochalasin B-block method, chromosome breakage, and SCE induction. Peripheral blood smears were also made for scoring MN in erythrocytes. There was a significant concentration-related elevation of SCE frequency in lymphocytes from the spleen and the peripheral blood as well as in cells from the lung. However, no statistically significant concentration-related increases were found in the frequency of chromosome aberrations in the cultured splenocytes or lung cells, and no significant increases in MN frequencies were observed in binucleated splenocytes or normochromatic erythrocytes in peripheral blood smears. C1 US EPA,RES TRIANGLE PK,NC 27711. ENVIRONM HLTH RES & TESTING INC,RES TRIANGLE PK,NC. NIEHS,RES TRIANGLE PK,NC 27709. NR 21 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1992 VL 280 IS 1 BP 35 EP 43 DI 10.1016/0165-1218(92)90016-S PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JC401 UT WOS:A1992JC40100005 PM 1377343 ER PT J AU EDLER, L AF EDLER, L TI STATISTICAL-METHODS FOR SHORT-TERM TESTS IN GENETIC TOXICOLOGY - THE 1ST 15 YEARS SO MUTATION RESEARCH LA English DT Review DE AMES TEST, DESIGN AND ANALYSIS; GENOTOXICOLOGY; SHORT-TERM TESTS; STATISTICAL METHODS ID SALMONELLA-MICROSOME TEST; HAMSTER OVARY CELLS; AMES TEST DATA; DOSE-RESPONSE; MUTAGENICITY DATA; MICRONUCLEUS TEST; POISSON REGRESSION; LINEAR-MODELS; ASSAY; PROPORTIONS AB Short-term tests (STTs) for detecting and assessing genotoxic or mutagenic effects have catalyzed the development of biostatistical methods for more than one decade. Most notably, the Ames Salmonella/microsome assay created statistical methodology with a range of applications going beyond genotoxicity. Early approaches with parametric statistical methods appeared to be insufficient and have been replaced by non-parametric ones requiring less restrictive distributional assumptions. There have also been successful attempts to use biomathematical models for establishing dose-response relationships. Overdispersion has been recognized as a major problem for the evaluation of mutagenic count data and methods to cope with it have became available. A theory of generalized linear modelling is emerging to combine dose-response modeling with much less restrictive distributional assumptions, while allowing the inclusion of concomitant factors arising from the experimental conditions. The methodological survey below reviews the present state of this development and is intended to promote further research into biostatistical issues and methods of analysis. Appropriate methods for the design and analysis of STTs are discussed. The progress for the Ames assay was only partially transmitted to the analysis of the large number of other short-term assays. Several such assays are reviewed with respect to their present state of statistical evaluation. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. NR 125 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES JI Mutat. Res. PD JUL PY 1992 VL 277 IS 1 BP 11 EP 33 DI 10.1016/0165-1110(92)90024-4 PG 23 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA HZ214 UT WOS:A1992HZ21400002 PM 1376440 ER PT J AU JONG, SC HO, HH MCMANUS, C KRICHEVSKY, MI AF JONG, SC HO, HH MCMANUS, C KRICHEVSKY, MI TI COMPUTER CODING OF STRAIN FEATURES OF THE GENUS PYTHIUM SO MYCOTAXON LA English DT Article ID DNA AB The fungal genus Pythium is a large group of aquatic and terrestrial species that are essentially worldwide in distribution. Identification of Pythium isolates to species level is often difficult because species are separated mainly by quantitative differences in the morphology of reproductive structures that are frequently overlapping in some species or absent in others. A data coding system used for computer storage and analysis of microbial strain data was expanded to include features specifically applicable to the identification of Pythium species. C1 SUNY COLL NEW PALTZ,NEW PALTZ,NY 12561. NIDR,MICROBIAL SYSTEMAT SECT,BETHESDA,MD 20892. RP JONG, SC (reprint author), AMER TYPE CULTURE COLLECT,12301 PARICLAWN DR,ROCKVILLE,MD 20852, USA. NR 31 TC 3 Z9 3 U1 0 U2 0 PU MYCOTAXON LTD PI ITHACA PA PO BOX 264, ITHACA, NY 14851-0264 SN 0093-4666 J9 MYCOTAXON JI Mycotaxon PD JUL-SEP PY 1992 VL 44 IS 2 BP 301 EP 314 PG 14 WC Mycology SC Mycology GA JC643 UT WOS:A1992JC64300004 ER PT J AU BOINSKI, S AF BOINSKI, S TI MONKEYS WITH INFLATED SEX APPEAL SO NATURAL HISTORY LA English DT Article C1 NIH,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RP BOINSKI, S (reprint author), UNIV FLORIDA,DEPT ANTHROPOL,GAINESVILLE,FL 32611, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER MUSEUM NAT HISTORY PI NEW YORK PA ATTN: LIBRARY SERIALS UNIT CENTRAL PK WEST AT 79TH ST, NEW YORK, NY 10024-5192 SN 0028-0712 J9 NAT HIST JI Nat. Hist. PD JUL PY 1992 IS 7 BP 42 EP 49 PG 8 WC Biodiversity Conservation; Ecology SC Biodiversity & Conservation; Environmental Sciences & Ecology GA HY892 UT WOS:A1992HY89200012 ER PT J AU COMPTON, JG DIGIOVANNA, JJ SANTUCCI, SK KEARNS, KS AMOS, CI ABANGAN, DL KORGE, BP MCBRIDE, OW STEINERT, PM BALE, SJ AF COMPTON, JG DIGIOVANNA, JJ SANTUCCI, SK KEARNS, KS AMOS, CI ABANGAN, DL KORGE, BP MCBRIDE, OW STEINERT, PM BALE, SJ TI LINKAGE OF EPIDERMOLYTIC HYPERKERATOSIS TO THE TYPE-II KERATIN GENE-CLUSTER ON CHROMOSOME-12Q SO NATURE GENETICS LA English DT Article ID CYTOKERATIN GENES; COMPLETE SEQUENCE; LOCALIZATION AB We investigated the molecular genetics of epidermolytic hyperkeratosis (EHK), a dominant disorder characterized by epidermal blistering, hyperkeratosis, vacuolar degeneration and clumping of keratin filaments. Based on this pathology, we have excluded by linkage analysis several candidate genes for the disease; in contrast, complete linkage was obtained with the type II keratin, K1, on 12q11-q13. Linkage in this region of chromosome 12 was confirmed using several other markers, and multi-locus linkage analyses further supported this location. Keratins are excellent EHK gene candidates since their expression is specific to the suprabasal epidermal layers. In the pedigree studied here, a type II keratin gene, very probably K1, is implicated as the site of the molecular defect causing EHK. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAG,BETHESDA,MD 20892. NR 36 TC 91 Z9 94 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1992 VL 1 IS 4 BP 301 EP 305 DI 10.1038/ng0792-301 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA JC984 UT WOS:A1992JC98400016 PM 1284546 ER PT J AU RINZEL, J FRANKEL, P AF RINZEL, J FRANKEL, P TI ACTIVITY PATTERNS OF A SLOW SYNAPSE NETWORK PREDICTED BY EXPLICITLY AVERAGING SPIKE DYNAMICS SO NEURAL COMPUTATION LA English DT Article ID REPETITIVE ACTIVITY; NEURONS; CIRCUITS; MODEL AB When postsynaptic conductance varies slowly compared to the spike generation process, a straightforward averaging scheme can be used to reduce the system's complexity. Our model consists of a Hodgkin-Huxley-like membrane description for each cell; synaptic activation is described by first order kinetics, with slow rates, in which the equilibrium activation is a sigmoidal function of the presynaptic voltage. Our work concentrates on a two-cell network and it applies qualitatively to the activity patterns, including bistable behavior, recently observed in simple in vitro circuits with slow synapses (Kleinfeld et al. 1990). The fact that our averaged system is derived from a realistic biophysical model has important consequences. In particular, it can preserve certain hysteresis behavior near threshold that is not represented in a simple ad hoc sigmoidal input-output network. This behavior enables a coupled pair of cells, one excitatory and one inhibitory, to generate an alternating burst rhythm even though neither cell has fatiguing properties. C1 BROWN UNIV,DIV APPL MATH,PROVIDENCE,RI 02912. RP RINZEL, J (reprint author), NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD JUL PY 1992 VL 4 IS 4 BP 534 EP 545 DI 10.1162/neco.1992.4.4.534 PG 12 WC Computer Science, Artificial Intelligence SC Computer Science GA JF872 UT WOS:A1992JF87200005 ER PT J AU CUNNINGHAM, ET WADA, E CARTER, DB TRACEY, DE BATTEY, JF DESOUZA, EB AF CUNNINGHAM, ET WADA, E CARTER, DB TRACEY, DE BATTEY, JF DESOUZA, EB TI DISTRIBUTION OF TYPE-I INTERLEUKIN-1 RECEPTOR MESSENGER-RNA IN TESTIS - AN INSITU HISTOCHEMICAL-STUDY IN THE MOUSE SO NEUROENDOCRINOLOGY LA English DT Article DE EPIDIDYMIS; HYBRIDIZATION INSITU; INTERLEUKIN-1; LEYDIG CELLS; RECEPTORS; SERTOLI CELLS; TESTIS ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE-INDUCED DIFFERENTIATION; PORCINE GRANULOSA-CELLS; RAT; SECRETION; STEROIDOGENESIS; MACROPHAGES; PHYSIOLOGY; EXPRESSION; CULTURES AB The cytokine interleukin-I (IL-1) has been reported to inhibit the hypothalamic-pituitary-gonadal axis, both through actions in brain and at the gonadal level. Recently, high affinity binding sites for I-125-recombinant human IL-1-alpha have been identified in the mouse testis with characteristics similar to those of type I IL-1 receptors on T lymphocytes and fibroblasts. The present study employed in situ hybridization histochemistry with S-35-labeled antisense cRNA probes derived from a murine type I IL-1 receptor cDNA to identify type I IL-1 receptor mRNA in the mouse testis. An intense signal was observed over interstitial cells, and over the cytoplasm of the epithelium of epididymal ducts, most prominently in the head region. The signal over seminiferous tubules, and over sperm cells within tubules and epididymal ducts, was comparable to background. This distribution of type I IL-1 receptor mRNA was similar to that recently reported for I-125-IL-1-alpha binding sites, and supports evidence implicating IL-1 as a direct regulator of gonadal function. C1 NIDA,ADDICT RES CTR,NEUROBIOL LAB,BALTIMORE,MD. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. UPJOHN CO,MOLEC BIOL,KALAMAZOO,MI 49001. UPJOHN CO,HYPERSENSITIV DIS RES,KALAMAZOO,MI 49001. NR 41 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1992 VL 56 IS 1 BP 94 EP 99 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA JC216 UT WOS:A1992JC21600013 PM 1386414 ER PT J AU LUGER, A WATSCHINGER, B DEUSTER, P SVOBODA, T CLODI, M CHROUSOS, GP AF LUGER, A WATSCHINGER, B DEUSTER, P SVOBODA, T CLODI, M CHROUSOS, GP TI PLASMA GROWTH-HORMONE AND PROLACTIN RESPONSES TO GRADED-LEVELS OF ACUTE EXERCISE AND TO A LACTATE INFUSION SO NEUROENDOCRINOLOGY LA English DT Article DE GROWTH HORMONE; PROLACTIN; LACTATE; EXERCISE ID METABOLIC RESPONSES; STRESS; SECRETION; MEN; RELEASE AB The effect of acute exercise at three graded intensities on plasma growth hormone (GH) and prolactin (PRL) concentrations was examined in three groups of healthy male volunteers. According to their training status these subjects were divided into untrained, moderately trained and highly trained. A clear response of GH to exercise was registered already at an intensity of 50% of maximal oxygen uptake (V(O2max)) with a maximal response at 70% V(O2max) and no further effect at 90% V(O2max). In contrast, no PRL response was observed at 50% V(O2max), a small PRL rise was seen at 70% V(O2max) and the highest response occurred at 90% V(O2max). Basal and exercise-stimulated plasma GH and PRL concentrations were similar in the three groups tested at similar relative workloads, suggesting that physical training induces adaptive changes whereby higher absolute workloads induce similar hormonal and metabolic changes. To examine a potential causative role of lactate in inducing the GH and PRL responses, sodium L-lactate was infused intravenously to normal sedentary volunteers at doses producing plasma lactate concentrations within the range of those seen between 70 and 90% V(O2max). This resulted in a significant elevation of plasma GH and PRL concentrations, which, however, were smaller than those obtained at an exercise-induced matched plasma lactate concentration. We conclude that physical training causes adaptive changes in highly trained runners so that identical GH and PRL responses to exercise are recorded at higher absolute workloads. Lactate may be involved in the exercise-induced GH and PRL response; however, it does not appear to play an exclusive role. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT MIL MED,HUMAN PERFORMANCE LAB,BETHESDA,MD 20814. RP LUGER, A (reprint author), UNIV VIENNA,DEPT MED 2,WAHRINGER GURTEL 18-20,A-1090 VIENNA,AUSTRIA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 27 TC 78 Z9 79 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1992 VL 56 IS 1 BP 112 EP 117 DI 10.1159/000126912 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA JC216 UT WOS:A1992JC21600016 PM 1641069 ER PT J AU KURTZKE, JF PAGE, WF MURPHY, FM NORMAN, JE AF KURTZKE, JF PAGE, WF MURPHY, FM NORMAN, JE TI EPIDEMIOLOGY OF MULTIPLE-SCLEROSIS IN UNITED-STATES VETERANS .4. AGE AT ONSET SO NEUROEPIDEMIOLOGY LA English DT Article DE MULTIPLE SCLEROSIS, AGE AT ONSET; MULTIPLE SCLEROSIS, GEOGRAPHY; MULTIPLE SCLEROSIS, MIGRATION; MULTIPLE SCLEROSIS, UNITED-STATES VETERANS ID RISK AB Age at onset of multiple sclerosis (MS) symptoms was ascertained for subsets of some 4,400 veterans of World War II who had been adjudged 'service-connected' for this condition. Average age at onset was 27.0 years for white men, 27.7 for white women, and 27.5 for black men. The unexpectedly older age for women is attributed to their older age at entry into service. When the coterminous United States was divided into three horizontal tiers of states, we found a strong effect of geography on age at onset. By state of residence at entry into active duty (EAD), white men had an average age at onset of 26.4 years in the northern tier, 27.3 years in the middle, and 28.8 years in the south. Trends were similar for white women and black men. Migrants, defined as those whose birth and EAD tiers differed, showed increasing ages at onset with southward moves. A statistical model used to discriminate between the influence of birth and EAD tiers on age at onset confirmed the significant effect of EAD alone. These data are compatible with the theses that the cause of MS is less common (or less efficient) in locations where the clinical disease is less common, and that its acquisition therefore occurs at an older age in those locales. C1 DEPT VET AFFAIRS MED CTR,NEUROEPIDEMIOL RES PROGRAM,WASHINGTON,DC. DEPT VET AFFAIRS MED CTR,NEUROL SERV,WASHINGTON,DC. NHLBI,BETHESDA,MD 20892. NATL ACAD SCI,INST MED,MED FOLLOW UP AGCY,WASHINGTON,DC 20418. NR 15 TC 21 Z9 21 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD JUL-DEC PY 1992 VL 11 IS 4-6 BP 226 EP 235 DI 10.1159/000110935 PG 10 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA KK601 UT WOS:A1992KK60100008 PM 1291886 ER PT J AU BRASILNETO, JP COHEN, LG PASCUALLEONE, A JABIR, FK WALL, RT HALLETT, M AF BRASILNETO, JP COHEN, LG PASCUALLEONE, A JABIR, FK WALL, RT HALLETT, M TI RAPID REVERSIBLE MODULATION OF HUMAN MOTOR OUTPUTS AFTER TRANSIENT DEAFFERENTATION OF THE FOREARM - A STUDY WITH TRANSCRANIAL MAGNETIC STIMULATION SO NEUROLOGY LA English DT Article ID REORGANIZATION FOLLOWING MOTOR; DIGIT AMPUTATION; ADULT-RATS; SOMATOSENSORY CORTEX; DYNAMIC ORGANIZATION; CEREBRAL-CORTEX; TARGET MUSCLES; NERVE LESIONS; REPRESENTATION; RESPONSES AB Reorganization of corticospinal pathways after spinal cord injury and amputations leads to increased excitability of motor pathways targeting muscles proximal to the level of interruption of efferents from the CNS. To study the timing of these changes, we have recorded motor evoked potentials (MEPs) in the arm muscles of three normal subjects before, during, and after anesthetic block of the forearm and hand. The amplitudes of MEPs from biceps, which was the muscle immediately proximal to the block, gradually increased with anesthesia and then returned to preanesthesia levels within approximately 20 minutes after anesthesia was ended. MEPs from the contralateral arm were unaffected. Such rapid changes strongly suggest unmasking of preexisting synaptic connections, due to disinhibition at cortical or subcortical levels, as the mechanism underlying acute modulation of motor outputs. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BLDG 10,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,ANESTHESIOL SERV,BETHESDA,MD 20892. RI Pascual-Leone, Alvaro/G-6566-2011 NR 27 TC 206 Z9 210 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1992 VL 42 IS 7 BP 1302 EP 1306 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA JC955 UT WOS:A1992JC95500010 PM 1620338 ER PT J AU PAIK, CH SOOD, VK LE, N CIOLOCA, L CARRASQUILLO, JA REYNOLDS, JC NEUMANN, RD REBA, RC AF PAIK, CH SOOD, VK LE, N CIOLOCA, L CARRASQUILLO, JA REYNOLDS, JC NEUMANN, RD REBA, RC TI RADIOLABELED PRODUCTS IN RAT-LIVER AND SERUM AFTER ADMINISTRATION OF ANTIBODY-AMIDE-DTPA-INDIUM-111 SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID INDIUM-111-LABELED MONOCLONAL-ANTIBODY; NORMAL TISSUE; IN-111; MICE; TUMOR; DTPA; RADIOIMMUNODETECTION; METABOLISM; CHELATE; BIODISTRIBUTION AB Anti-human serum albumin antibody (Ab) was used as a model antibody. Ab was conjugated with DTPA using cyclic DTPA dianhydride reaction and radiolabeled with In-111. The labeled Ab was purified by affinity chromatography. Size exclusion HPLC of this product showed 62% of In-111 bound to monomeric Ab and 38% of the activity bound to antibody oligomers with molecular weights ranging from 300.000 to 450,000. The labeled antibody preparation was injected into the tail vein of rats. The radioactive substances in serum and the supernatant from liver homogenates were analyzed for molecular weight and immunoreactivity. Size exclusion HPLC of the serum samples indicated that the monomeric and dimeric Abs disappeared from the serum at a similar rate over a 48 h period. In addition, a new radioactive substance with an estimated molecular weight of 35,000 appeared in the serum. The immunoreactive fraction of the circulating In-111 substances decreased slowly, somewhat proportional to the appearance of the metabolite. On the other hand, the immunoreactivity of the In-111 substances in the supernatant from the liver homogenate decreased rapidly and no appreciable immunoreactivity was observed after 48 h. The labeled antibody was catabolized very rapidly in the liver and the major activity in the supernatant was associated with a small molecular weight metabolite which had a HPLC retention time identical to that of DTPA-In-111. The second metabolite had an estimated molecular weight of 35,000. No radioactivity was associated with transferrin. C1 GEORGE WASHINGTON UNIV,MED CTR,DIV NUCL MED,RADIOPHARMACEUT CHEM SECT,WASHINGTON,DC 20037. RP PAIK, CH (reprint author), NIH,DEPT NUCL MED,WARREN G MAGNUSON CLIN CTR,BLDG 21,ROOM 136,BETHESDA,MD 20892, USA. RI Sood, Vinay/B-7109-2008; Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 30 TC 24 Z9 25 U1 0 U2 1 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 JUL PY 1992 VL 19 IS 5 BP 517 EP 522 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HZ339 UT WOS:A1992HZ33900002 ER PT J AU SEGATTO, O LONARDO, F HELIN, K WEXLER, D FAZIOLI, F RHEE, SG DIFIORE, PP AF SEGATTO, O LONARDO, F HELIN, K WEXLER, D FAZIOLI, F RHEE, SG DIFIORE, PP TI ERBB-2 AUTOPHOSPHORYLATION IS REQUIRED FOR MITOGENIC ACTION AND HIGH-AFFINITY SUBSTRATE COUPLING SO ONCOGENE LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PHOSPHOLIPASE-C-GAMMA; PHOSPHOTYROSINE-CONTAINING PROTEINS; TYROSINE KINASE-ACTIVITY; FACTOR RECEPTOR; EGF RECEPTOR; ONCOGENE PRODUCT; NEU ONCOGENE; 3T3 CELLS; GENE AB Autophosphorylation of gp185(erbB-2) in vivo is confined to its carboxy terminus and is required for optimal erbB-2 transforming activity under conditions of receptor overexpression. It remains unresolved, however, to what extent autophosphorylation regulates erhB-2 mitogenic signaling in normal cells, nor is the biochemical basis for such a regulatory function known. To address these issues, we utilized a chimeric molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and intracellular domains of the erbB-2 product. In this EGFR/erbB-2 chimera, erbB-2 kinase activity is regulated by EGF binding. An EGFR/erbB-2 mutant bearing multiple Tyr --> Phe substitutions at erbB-2 autophosphorylation sites (EGFR/erbB-2 5P) displayed markedly reduced phosphotyrosine content following EGF stimulation in comparison with the non-mutated chimera. When expressed in NR6 cells, the EGFR/erhB-2 5P mutant was unable to deliver a sizeable mitogenic signal when activated by EGF at physiological levels. In intact cells, the 5P mutant was still able to stimulate phosphorylation of the gamma-isozyme of phospholipase C (PLC-gamma), a prototype erhB-2 substrate, although with a delayed time course, indicating that the 5P mutation decreased the affinity of the erbB-2 kinase for this substrate. This conclusion was further supported by the inability of the 5P mutant to associate with PLC-gamma in co-immunoprecipitation experiments. We infer that a major role of autophosphorylation is to increase the affinity of the erbB-2 kinase for its cellular substrates, so that, under physiological conditions, autophosphorylation is absolutely required for erbB-2 mitogenic signaling. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1D23,BETHESDA,MD 20892. REGINA ELENA INST CANC RES,I-00158 ROME,ITALY. UNIV COPENHAGEN,INST MICROBIOL,DK-1168 COPENHAGEN,DENMARK. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 41 TC 20 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1992 VL 7 IS 7 BP 1339 EP 1346 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HZ971 UT WOS:A1992HZ97100012 PM 1352397 ER PT J AU FLEMING, TP MATSUI, T HEIDARAN, MA MOLLOY, CJ ARTRIP, J AARONSON, SA AF FLEMING, TP MATSUI, T HEIDARAN, MA MOLLOY, CJ ARTRIP, J AARONSON, SA TI DEMONSTRATION OF AN ACTIVATED PLATELET-DERIVED GROWTH-FACTOR AUTOCRINE PATHWAY AND ITS ROLE IN HUMAN TUMOR-CELL PROLIFERATION INVITRO SO ONCOGENE LA English DT Article ID SIMIAN SARCOMA-VIRUS; SIS-TRANSFORMED-CELLS; V-SIS; FACTOR RECEPTORS; GENE; EXPRESSION; CDNA; STIMULATION; SURAMIN; CLONING AB In tumor cells expressing platelet-derived growth factor (PDGF) ligand(s) and receptor(s), immunoblot analysis established tyrosine phosphorylation of PDGF receptors (PDGFRs) in the absence of any exogenous ligand, implying chronic receptor activation. Exposure to suramin resulted in diminished receptor autophosphorylation and/or up-regulation of receptor protein. In a subset of such tumor lines, there was a marked reduction in DNA synthesis in response to suramin or PDGF-neutralizing antiserum. These findings demonstrate that autocrine PDGF stimulation contributes to proliferation of some human tumors and that agents which interfere with ligand-receptor interactions at the cell surface can significantly interfere in this process. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892. RI Matsui, Toshimitsu/E-8065-2010; Molloy, Christopher/A-6821-2013 OI Molloy, Christopher/0000-0003-2964-6166 NR 31 TC 51 Z9 52 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1992 VL 7 IS 7 BP 1355 EP 1359 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HZ971 UT WOS:A1992HZ97100014 PM 1320245 ER PT J AU LASA, MSM DATILES, MB PODGOR, MJ MAGNO, BV AF LASA, MSM DATILES, MB PODGOR, MJ MAGNO, BV TI CONTRAST AND GLARE SENSITIVITY - ASSOCIATION WITH THE TYPE AND SEVERITY OF THE CATARACT SO OPHTHALMOLOGY LA English DT Article ID VISUAL-ACUITY; VISION AB Purpose: Contrast and glare sensitivity tests are now being used as adjuncts to visual acuity in the assessment of visual function. Limited data are available on the associations of the former tests with cataract type and severity. The aim of the study is to assess these associations using standardized techniques. Methods: Contrast sensitivity tests (using the Pelli-Robson chart) and glare sensitivity tests (using the Vistech MCT 8000) were done on 128 patients with cataracts and no other ocular disease and on 29 control volunteers. The cataracts were graded using the Lens Opacities Classification System II (LOCS II). Data from the left eyes were analyzed using logistic regression models. Results: Contrast sensitivity loss was associated with cataract severity for cortical (P < 0.0001) and posterior subcapsular (P = 0.0001) cataracts and with decreased visual acuity (P = 0.0001). Night and day glare sensitivity were each associated only with increased severity of posterior subcapsular cataracts (P less-than-or-equal-to 0.003) and with decreased visual acuity (P < 0.001). Additional analyses showed that contrast and glare sensitivity were similar in eyes with no cataracts and early cataracts. Conclusion: These results suggest that the Pelli-Robson Chart and the Vistech MCT 8000 are good techniques for evaluating visual function in moderate to advanced cataracts. However, for early cataracts, other techniques need to be explored to assess visual function loss. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,RM 10N226,BETHESDA,MD 20892. NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 20 TC 23 Z9 25 U1 1 U2 9 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1992 VL 99 IS 7 BP 1045 EP 1049 PG 5 WC Ophthalmology SC Ophthalmology GA JC543 UT WOS:A1992JC54300018 PM 1495782 ER PT J AU WEISS, JS RODRIGUES, MM KRUTH, HS RAJAGOPALAN, S RADER, DJ KACHADOORIAN, H AF WEISS, JS RODRIGUES, MM KRUTH, HS RAJAGOPALAN, S RADER, DJ KACHADOORIAN, H TI PANSTROMAL SCHNYDERS CORNEAL-DYSTROPHY - ULTRASTRUCTURAL AND HISTOCHEMICAL-STUDIES SO OPHTHALMOLOGY LA English DT Article ID CRYSTALLINE STROMAL DYSTROPHY; ULTRATHIN FROZEN-SECTIONS; UNESTERIFIED CHOLESTEROL; CLINICAL-FEATURES; DEFICIENCY; MICROSCOPY; LIGHT; LOCALIZATION; METABOLISM; DISEASE AB Background: A large cohort comprising four kindreds of patients with Schnyder's dystrophy has been identified in central Massachusetts. All patients were Swede-Finn with ancestry from the southwest Finnish coast on the Bay of Bothnia. Methods: Of 60 members of this cohort examined by one of the authors (JSW), 18 had evidence of Schnyder's dystrophy. One femal with Schnyder's dystrophy from each of three kindreds underwent penetrating keratoplasty for decreased visual acuity. We examined 4 corneal buttons from these unrelated women, aged 47, 63, and 72 years. Results: The fluorescent probe filipin revealed that the majority of the lipid deposits were rich in unesterified cholesterol. Electron microscopy demonstrated abnormal accumulation of lipid and dissolved cholesterol in the epithelium, Bowman's layer, and throughout the stroma. Examination of the kindreds reflected the variable expression of crystals, which were present only in two patients, the 47-year-old and 63-year-old women. Conclusion: Ultrastructural and histochemical studies showed the panstromal localization of lipid in Schnyder's corneal dystrophy in three patients with Schnyder's dystrophy who underwent penetrating keratoplasty. C1 UNIV MARYLAND,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21201. NHLBI,MOLEC DIS BRANCH,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892. RP WEISS, JS (reprint author), UNIV MASSACHUSETTS,SCH MED,DEPT SURG,DIV OPHTHALMOL,ROOM S7-834,55 LAKE AVE N,WORCESTER,MA 01655, USA. NR 36 TC 30 Z9 29 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1992 VL 99 IS 7 BP 1072 EP 1081 PG 10 WC Ophthalmology SC Ophthalmology GA JC543 UT WOS:A1992JC54300023 PM 1495786 ER PT J AU RUTTIMANN, UE WEBBER, RL HAZELRIG, JB AF RUTTIMANN, UE WEBBER, RL HAZELRIG, JB TI FRACTAL DIMENSION FROM RADIOGRAPHS OF PERIDONTAL ALVEOLAR BONE - A POSSIBLE DIAGNOSTIC INDICATOR OF OSTEOPOROSIS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID SUBTRACTION RADIOGRAPHY AB The purpose of this study was to investigate whether a radiographic estimate of osseous fractal dimension is useful in the characterization of structural changes in alveolar bone. Ten dry mandibular bone segments were radiographed from three controlled projection angles (-5, 0, +5 degrees), before and after acid-induced partial decalcification. Fractal dimension was estimated by regression analysis of power spectra computed by Fourier transform of selected regions of interest in digitized images of the radiographs. Repeated-measures ANOVA showed that fractal dimension so determined varied over anatomic locations (p < .01), but increased after acid-induced demineralization (p < .0005), irrespective of the radiographic projection angles (p > .99). In vivo fractal dimension was computed from randomly selected intraoral radiographs of six premenopausal (ages, 32.8 +/- 3.9) and six postmenopausal (ages, 62.5 +/- 4.1) women. A significantly (p < .01) higher fractal dimension was observed in the older group. C1 BOWMAN GRAY SCH MED,DEPT DENT,MED CTR BLVD,WINSTON SALEM,NC 27157. BOWMAN GRAY SCH MED,DEPT RADIOL,WINSTON SALEM,NC 27157. NIDR,DIAGNOST SYST BRANCH,BETHESDA,MD 20892. UNIV ALABAMA,BIRMINGHAM,AL 35294. NR 27 TC 120 Z9 121 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUL PY 1992 VL 74 IS 1 BP 98 EP 110 DI 10.1016/0030-4220(92)90222-C PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JD623 UT WOS:A1992JD62300018 PM 1508517 ER PT J AU CLARK, AP SCHUTTINGA, JA AF CLARK, AP SCHUTTINGA, JA TI TARGETED ESTROGEN PROGESTOGEN REPLACEMENT THERAPY FOR OSTEOPOROSIS - CALCULATION OF HEALTH-CARE COST SAVINGS SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE BONE MINERAL DENSITY SCREENING; HEALTH CARE COSTS; HIP FRACTURE; HORMONE REPLACEMENT THERAPY; OSTEOPOROSIS ID POSTMENOPAUSAL WOMEN; BONE DENSITOMETRY; HIP FRACTURE; WHITE WOMEN; RISK; FOREARM; MASS AB Osteoporosis is a crippling affliction in which bone mass decreases, making it more susceptible to fracture. In postmenopausal women it presents most often as a hip, spinal, or forearm fracture. Adult women face a 15% lifetime risk of a hip fracture, and the annual costs of hip fractures alone are estimated at $7.3 billion in the United States. Since the 1970s, estrogen/progestogen therapy has been recognized as an effective intervention that reduces the risk of fractures. Recently, the development of methods for accurately determining bone mass and thus helping to predict bone fracture risk has made this intervention attractive for use in a targeted population. This report analyzes the health care costs and calculates the cost savings of coupling bone mineral density screening at the time of menopause with long-term estrogen/progestogen therapy for those most at risk for developing fractures. The model assumes that a cohort of 100000 American white women, aged 50, are screened for bone mineral density and that 90% of the high-risk group (density <0.85 g/cm3) and 70% of the mid-risk group (density between 0.85 and 1.00 g/cm3) elect to take hormone replacement therapy for 15 years. Based on calculations of the costs of screening and hormone replacement therapy, and the savings in cost of treatment and lost productivity from reduced fractures, it is estimated that the present value of savings in cost of illness for this cohort over a 40-year period is $5.1 million. In present value terms, total net savings of $27.6 million attributable to screening and hormonal therapy are projected, over a 40-year period, assuming that 50% of the 1.09 million American white women who reached age 50 in 1988 are screened as described for the cohort. Similar, if not greater, savings could be expected for populations reaching age 50 in subsequent years. C1 NIH,OFF DIRECTOR,OFF SCI POLICY LEGISLAT,BETHESDA,MD 20892. RP CLARK, AP (reprint author), NIH,DIV RES GRANTS,5333 WESTBARD AVE,RM A10,BETHESDA,MD 20892, USA. NR 21 TC 28 Z9 28 U1 2 U2 2 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING, SURREY, ENGLAND GU7 3DJ SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JUL PY 1992 VL 2 IS 4 BP 195 EP 200 DI 10.1007/BF01623926 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JB386 UT WOS:A1992JB38600007 PM 1611225 ER PT J AU MAX, MB AF MAX, MB TI UNITED-STATES GOVERNMENT DISSEMINATES ACUTE PAIN TREATMENT GUIDELINES - WILL THEY MAKE A DIFFERENCE SO PAIN LA English DT Article RP MAX, MB (reprint author), NIDR,PAW RES CLIN,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 10,ROOM 3C-405,BETHESDA,MD 20892, USA. NR 6 TC 3 Z9 3 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 JUL PY 1992 VL 50 IS 1 BP 3 EP 4 DI 10.1016/0304-3959(92)90106-L PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA JH084 UT WOS:A1992JH08400001 PM 1381069 ER PT J AU ARGENT, BE GITHENS, S KALSER, S LONGNECKER, DS METZGAR, R WILLIAMS, JA AF ARGENT, BE GITHENS, S KALSER, S LONGNECKER, DS METZGAR, R WILLIAMS, JA TI THE PANCREATIC DUCT CELL SO PANCREAS LA English DT Article DE PANCREATIC DUCTS AB A conference entitled "The Pancreatic Duct Cell: Physiology and Pathophysiology" was held September 26-29, 1991, at the Engineering Society Club of Baltimore. The conference was organized by a committee consisting of John Williams of the University of Michigan (Co-Chair), Daniel Longnecker of Dartmouth Medical School (Co-Chair), Barry Argent of Newcastle Upon Tyne, Raymond Frizzell of the University of Alabama at Birmingham, Sherwood Githens of the University of New Orleans, and Sarah Kalser of the NIDDK. The meeting was sponsored by the NIDDK with contributions from NCI, NIDR, ADAMHA, and the American Gastroenterological Association. About 100 investigators from the United States, England, Canada, Germany, Norway, and Israel attended the conference. The participants were based in a number of distinct disciplines including both basic and clinical sciences. While the main focus was on pancreatic ducts, comparison of salivary and bile ducts was also included. C1 NIDDKD,WESTWOOD BLDG,RM 3A-17,5333 WESTBARD AVE,BETHESDA,MD 20892. OI Williams, John/0000-0002-6063-7615 NR 0 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 1992 VL 7 IS 4 BP 403 EP 419 DI 10.1097/00006676-199207000-00001 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JA638 UT WOS:A1992JA63800001 PM 1353627 ER PT J AU PATTO, RJ VINAYEK, R JENSEN, RT GARDNER, JD AF PATTO, RJ VINAYEK, R JENSEN, RT GARDNER, JD TI CARBACHOL DOES NOT DOWN-REGULATE SUBSTANCE-P RECEPTORS IN PANCREATIC ACINI SO PANCREAS LA English DT Article DE PANCREATIC ACINI; SUBSTANCE-P AB In a previous study, we found that first incubating guinea pig pancreatic acini with carbachol caused desensitization of the enzyme secretory response to cholecystokinin-octapeptide (CCK-8), bombesin, and carbachol but not that to substance P. This carbachol-induced desensitization could be accounted for by carbachol-induced down-regulation of receptors for CCK-8, bombesin, and carbachol. Although carbachol did not desensitize the enzyme secretory response to substance P, an effect of carbachol on substance P receptors was not examined. In the present study, in dispersed acini from guinea pig pancreas, substance P caused a twofold increase in amylase secretion. Stimulation was half-maximal at 0.7 nM and was maximal at 10 nM. Analysis of the ability of substance P to inhibit binding of I-125-substance P to substance P receptors indicated that acini possess a single class of receptors for substance P (K(d) = 0.8 +/- 0.1 nM; B(max) = 1,037 +/- 145 fmol/mg of DNA). There was a close correlation between the relative potency with which substance P stimulated amylase secretion (0.7 nM) and the potency for inhibiting binding of I-125-substance P (K(d) = 0.8 nM). First incubating pancreatic acini with carbachol did not alter either substance P-stimulated enzyme secretion or binding of I-125-substance P to substance P receptors, whereas in the same experiments, carbachol reduced binding of I-125-CCK-8 to cholecystokinin receptors by 50% and decreased in CCK-8-stimulated enzyme secretion by 50%. These findings indicate that there is specificity in the action of carbachol on secretagogue receptors in pancreatic acini in that carbachol reduces the number of receptors for cholecystokinin but does not alter the number of receptors for substance P. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD. NR 0 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 1992 VL 7 IS 4 BP 447 EP 452 DI 10.1097/00006676-199207000-00005 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JA638 UT WOS:A1992JA63800005 PM 1379366 ER PT J AU TRIGLIA, T WELLEMS, TE KEMP, DJ AF TRIGLIA, T WELLEMS, TE KEMP, DJ TI TOWARDS A HIGH-RESOLUTION MAP OF THE PLASMODIUM-FALCIPARUM GENOME SO PARASITOLOGY TODAY LA English DT Review ID YEAST ARTIFICIAL CHROMOSOMES; P-FALCIPARUM; SIZE VARIATION; LARGE SEGMENTS; PHYSICAL MAP; DELETIONS; CLONING; GENES; DNA; AMPLIFICATION AB Until recently very little was known about the genome of Plasmodium falciparum. The situation has changed considerably with the advent of pulsed field gradient electrophoresis and yeast artificial chromosome technologies. It should now be possible to generate a high-resolution map within a few years. Here, Tony Triglia, Thomas Wellems and David Kemp review current knowledge. C1 NIH,MALARIA RES LAB,BETHESDA,MD 20892. RP TRIGLIA, T (reprint author), ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,PARKVILLE,VIC 3050,AUSTRALIA. NR 47 TC 62 Z9 63 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUL PY 1992 VL 8 IS 7 BP 225 EP 229 DI 10.1016/0169-4758(92)90118-L PG 5 WC Parasitology SC Parasitology GA JA414 UT WOS:A1992JA41400006 PM 15463622 ER PT J AU NASH, T AF NASH, T TI SURFACE-ANTIGEN VARIABILITY AND VARIATION IN GIARDIA-LAMBLIA SO PARASITOLOGY TODAY LA English DT Review ID EXCRETORY-SECRETORY PRODUCTS; PROTEIN; GENE; IDENTIFICATION; HOMEODOMAIN; INFECTIONS; ANIMALS AB Recent studies show that Giardia isolates are heterogeneous but fall into at least three groups as determined by a number of complementary techniques. Giardia undergoes surface antigenic variation, both in vitro, and in humans and other animal model infections. Many of the characteristics of antigenic variation and the proteins involved, called variant-specific surface proteins (VSPs), are unique. The sequences of five VSPs reveal a family of cysteine-rich proteins. Here Theodore Nash reviews the relationship between antigenic variation and Giardia heterogeneity. RP NASH, T (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 37 TC 108 Z9 111 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUL PY 1992 VL 8 IS 7 BP 229 EP 234 DI 10.1016/0169-4758(92)90119-M PG 6 WC Parasitology SC Parasitology GA JA414 UT WOS:A1992JA41400007 PM 15463623 ER PT J AU POLI, G FAUCI, AS AF POLI, G FAUCI, AS TI THE ROLE OF MONOCYTE MACROPHAGES AND CYTOKINES IN THE PATHOGENESIS OF HIV-INFECTION SO PATHOBIOLOGY LA English DT Article DE MONOCYTE; MACROPHAGE; CYTOKINES; HIV; TRANSCRIPTION ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; PRIMARY MONONUCLEAR PHAGOCYTES; HUMAN PERIPHERAL-BLOOD; NF-KAPPA-B; FACTOR-ALPHA; BONE-MARROW; HTLV-III; PROGENITOR CELLS AB The monocyte/macrophage system, which is characterized by a high degree of heterogeneity, is a target of the human immunodeficiency virus (HIV) in vitro as well as in vivo. Both bone-marrow-derived precursor elements and circulating monocytes are infectable in vitro and have also been found infected in seropositive individuals. However, terminally differentiated macrophages are the most commonly infected cells found in vivo in addition to the CD4+ T lymphocytes. Several immunoregulatory cytokines have been shown to either up-regulate or suppress virus replication/expression in vitro in cells belonging to the monocyte/macrophage lineage by affecting both transcriptional as well as posttranscriptional events. The observation that elevated levels of several of these cytokines are present in HIV-infected individuals suggests that they may play an important role as regulators of virus expression in vivo. RP POLI, G (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 48 TC 74 Z9 74 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JUL-AUG PY 1992 VL 60 IS 4 BP 246 EP 251 DI 10.1159/000163729 PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA JL308 UT WOS:A1992JL30800010 PM 1388722 ER PT J AU VESIKARI, T RUUSKA, T GREEN, KY FLORES, J KAPIKIAN, AZ AF VESIKARI, T RUUSKA, T GREEN, KY FLORES, J KAPIKIAN, AZ TI PROTECTIVE EFFICACY AGAINST SEROTYPE-1 ROTAVIRUS DIARRHEA BY LIVE ORAL RHESUS-HUMAN REASSORTANT ROTAVIRUS VACCINES WITH HUMAN ROTAVIRUS VP7 SEROTYPE-1 OR SEROTYPE-2 SPECIFICITY SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE ROTAVIRUS VACCINE; RHESUS-HUMAN REASSORTANT ROTAVIRUSES; ROTAVIRUS IMMUNITY; VACCINE EFFICACY ID VENEZUELAN INFANTS; CHILDREN; TRIAL; ANTIBODIES; USA AB Rhesus-human rotavirus (RV) reassortant vaccine strains D x RRV or DS 1 x RRV with VP7 serotype 1 or 2 specificity were evaluated for safety, immunogenicity and protective efficacy in a double blind placebo-controlled three cell trial involving 359 infants ages 2 to 5 months. The titer of the D x RRV vaccine was 10(4) and that of the DS 1 x RRV vaccine was 10(5) plaque-forming units/1-ml dose. The vaccines were acceptably reactogenic, each inducing a transient febrile response in fewer than one-third of the vaccinees. Seroconversion by RV enzyme-linked immunosorbent assay IgA antibody was detected in 61 and 75% of the vaccinees receiving a single dose of the serotype 1 or 2 reassortant vaccine, respectively. Efficacy against RV diarrhea was evaluated in two successive epidemic seasons; RV serotype 1 was prevalent in both. Clinical efficacy was observed with both vaccines and was associated with seroconversion after vaccination; considering only such vaccinees both vaccines showed equal efficacy. The overall rates of protection for the two vaccines combined against clinical RV disease in children with seroconversion after vaccination were 92 and 59% in the first and second RV epidemic seasons, respectively. Protection against asymptomatic RV infection, as measured by serologic responses, was 59% in the first season and nil in the second season. It is concluded that each of the reassortant RV vaccines was effective in inducing protection against symptomatic RV disease associated with RV serotype 1. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP VESIKARI, T (reprint author), UNIV HOSP TAMPERE,DEPT BIOMED SCI,POB 60M,SF-33101 TAMPERE,FINLAND. NR 23 TC 50 Z9 51 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 JUL PY 1992 VL 11 IS 7 BP 535 EP 542 DI 10.1097/00006454-199207000-00006 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA JC746 UT WOS:A1992JC74600006 PM 1326741 ER PT J AU ROILIDES, E BUTLER, KM HUSSON, RN MUELLER, BU LEWIS, LL PIZZO, PA AF ROILIDES, E BUTLER, KM HUSSON, RN MUELLER, BU LEWIS, LL PIZZO, PA TI PSEUDOMONAS INFECTIONS IN CHILDREN WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE BACTERIAL INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PSEUDOMONAS SPP; XANTHOMONAS-MALTOPHILIA; CHILDREN ID BACTEREMIA; INVITRO; CANCER AB Thirteen bacteremias and 25 nonbacteremic infections caused by Pseudomonas spp. occurred in 22 of 236 children with human immunodeficiency virus infection with a rate of infection of 0.098 (bacteremia, 0.030) per patient year. Four patients were neutropenic (<500/-mu-l). Central venous catheter (CVC)-related infections were most frequent (n = 20) followed by otitis externa (n = 6) and pneumonia (n = 5). Pseudomonas aeruginosa was the most common isolate and caused both CVC-related and CVC-unrelated infections, whereas other Pseudomonas spp. and Xanthomonas maltophilia were almost exclusively associated with CVC-related infections. The children who received appropriate therapy had a favorable outcome. In 7 CVC-related infections (35%) the catheter was removed. Pseudomonas spp. are of increasing importance in human immunodeficiency virus-infected children causing significant morbidity and increased hospitalization. These infections may be life-threatening if appropriate therapy is not vigorously initiated. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N240,BETHESDA,MD 20892. NR 24 TC 44 Z9 45 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 1992 VL 11 IS 7 BP 547 EP 553 DI 10.1097/00006454-199207000-00008 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA JC746 UT WOS:A1992JC74600008 PM 1528645 ER PT J AU QUINN, TC RUFF, A HALSEY, N AF QUINN, TC RUFF, A HALSEY, N TI PEDIATRIC ACQUIRED-IMMUNODEFICIENCY-SYNDROME - SPECIAL CONSIDERATIONS FOR DEVELOPING-NATIONS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; CLINICAL CASE DEFINITION; HAITIAN INFANTS 6; 12 MONTHS OLD; VIRUS-INFECTION; HIV-INFECTION; MATERNAL ANTIBODIES; VERTICAL TRANSMISSION; OCCUPATIONAL EXPOSURE; CONCURRENT ILLNESSES C1 JOHNS HOPKINS UNIV,SCH MED,SCH HYG & PUBL HLTH,DEPT INT HLTH PEDIAT,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP QUINN, TC (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BLALOCK 1111,600 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-26521] NR 113 TC 22 Z9 22 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 JUL PY 1992 VL 11 IS 7 BP 558 EP 568 PG 11 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA JC746 UT WOS:A1992JC74600011 PM 1528647 ER PT J AU BENNETT, LC BIER, DM BRUSILOW, SW DANFORD, DE DIETZ, WH FERNSTROM, JD GARZA, C GRAVE, GD GREENE, HL HAMBIDGE, KM HEIRD, WC HILL, JG LEVIN, EY MARTORELL, R SACKS, F SPARKS, JW UNDERWOOD, LE WALKER, WA AF BENNETT, LC BIER, DM BRUSILOW, SW DANFORD, DE DIETZ, WH FERNSTROM, JD GARZA, C GRAVE, GD GREENE, HL HAMBIDGE, KM HEIRD, WC HILL, JG LEVIN, EY MARTORELL, R SACKS, F SPARKS, JW UNDERWOOD, LE WALKER, WA TI 5-YEAR PLAN FOR NUTRITION RESEARCH AND TRAINING - EXECUTIVE SUMMARY SO PEDIATRIC RESEARCH LA English DT Editorial Material C1 NICHHD,ENDOCRINOL NUTR & GROWTH BRANCH,EXECUT PLAZA N BLDG,ROOM 637,BETHESDA,MD 20892. RI Martorell, Reynaldo /I-2539-2012 NR 0 TC 0 Z9 0 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 JUL PY 1992 VL 32 IS 1 BP 1 EP 9 PG 9 WC Pediatrics SC Pediatrics GA HZ976 UT WOS:A1992HZ97600001 ER PT J AU KAUFFMAN, RE BANNER, W BERLIN, C GORMAN, RL LAMBERT, GH WILSON, G BENNETT, DR CORDERO, JF TOMICH, P LICATA, SA KAUFMAN, P TROENDLE, G YAFFE, SJ COTE, CJ SNODGRASS, W TEMPLE, AR AF KAUFFMAN, RE BANNER, W BERLIN, C GORMAN, RL LAMBERT, GH WILSON, G BENNETT, DR CORDERO, JF TOMICH, P LICATA, SA KAUFMAN, P TROENDLE, G YAFFE, SJ COTE, CJ SNODGRASS, W TEMPLE, AR TI RETINOID THERAPY FOR SEVERE DERMATOLOGICAL DISORDERS SO PEDIATRICS LA English DT Editorial Material C1 AMER MED ASSOC,CHICAGO,IL 60610. CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. PHARMACEUT MANUFACTURERS ASSOC,WASHINGTON,DC. NR 5 TC 12 Z9 12 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1992 VL 90 IS 1 BP 119 EP 120 PN 1 PG 2 WC Pediatrics SC Pediatrics GA JA854 UT WOS:A1992JA85400030 ER PT J AU CHANOCK, RM PARROTT, RH CONNORS, M COLLINS, PL MURPHY, BR AF CHANOCK, RM PARROTT, RH CONNORS, M COLLINS, PL MURPHY, BR TI SERIOUS RESPIRATORY-TRACT DISEASE CAUSED BY RESPIRATORY SYNCYTIAL VIRUS - PROSPECTS FOR IMPROVED THERAPY AND EFFECTIVE IMMUNIZATION SO PEDIATRICS LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; F-GLYCOPROTEIN; COTTON RATS; MONOCLONAL-ANTIBODIES; IMMUNOLOGICAL RESPONSE; VIRAL-INFECTION; IMMUNE-RESPONSE; SUBGROUP-A; INFANTS; CHILDREN C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,NATL MED CTR,WASHINGTON,DC 20010. NR 56 TC 67 Z9 68 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1992 VL 90 IS 1 SU S BP 137 EP 143 PG 7 WC Pediatrics SC Pediatrics GA JB167 UT WOS:A1992JB16700003 PM 1603639 ER PT J AU STOPA, EG UHL, GR OHARA, BF CHORSKY, RL KING, JC BIRD, ED WOLFE, H AF STOPA, EG UHL, GR OHARA, BF CHORSKY, RL KING, JC BIRD, ED WOLFE, H TI SOMATOSTATIN-GENE EXPRESSION IN THE POSTMORTEM ADULT AND FETAL HUMAN BRAIN SO PEPTIDE RESEARCH LA English DT Article ID MESSENGER-RNA; SENILE DEMENTIA; INSITU HYBRIDIZATION; CEREBRAL-CORTEX; NEUROPEPTIDE-Y; ALZHEIMER TYPE; IMMUNOREACTIVITY; DISEASE; NEURONS; LOCALIZATION AB We have examined the utility of in situ hybridization for detecting pre-prosomatostatin mRNA in postmortem human brain. In preliminary studies, Northern blot analysis using a rat model, which simulates the normal pattern of human postmortem brain cooling, revealed retention of significant amounts of hybridizable somatostatin mRNA relative to control levels between 12 and 24 hours after death. mRNA extracted from postmortem fetal human brain specimens showed hybridization to cRNA probes directed against preprosomatostatin mRNA. We thus undertook in situ hybridization studies. Antisense RNA probes were hybridized to neurons that expressed pre-prosomatostatin in 10-mu-m sections of adult and fetal human brain. The distribution of pre-prosomatostatin mRNA-containing neurons was similar to that observed for somatostatin-like immunoreactivity; however, the in situ hybridization technique was a more sensitive marker of neuronal perikarya. Our results indicate that hybridization to pre-prosomatostatin mRNA is a useful method for localizing these peptidergic neurons in postmortem human brain tissue. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. HARVARD UNIV,MCLEAN HOSP,BELMONT,MA 02178. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,BOSTON,MA 02111. RP STOPA, EG (reprint author), SUNY SYRACUSE,HLTH SCI CTR,DEPT PATHOL NEUROPATHOL,750 E ADAMS ST,SYRACUSE,NY 13210, USA. FU NIA NIH HHS [AG00295] NR 16 TC 6 Z9 6 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 1040-5704 J9 PEPTIDE RES JI Peptide Res. PD JUL-AUG PY 1992 VL 5 IS 4 BP 201 EP 205 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JH085 UT WOS:A1992JH08500004 PM 1384822 ER PT J AU ROTHMAN, RB BYKOV, V JACOBSON, AE RICE, KC LONG, JE BOWEN, WD AF ROTHMAN, RB BYKOV, V JACOBSON, AE RICE, KC LONG, JE BOWEN, WD TI A STUDY OF THE EFFECT OF THE IRREVERSIBLE DELTA-RECEPTOR ANTAGONIST [D-ALA(2),LEU(5),CYS(6)]-ENKEPHALIN ON DELTA(CX) AND DELTA(NCX) OPIOID BINDING-SITES INVITRO AND INVIVO SO PEPTIDES LA English DT Article DE [D-ALA(2),LEU(5),CYS(6)]ENKEPHALIN; DALCE; OPIOID RECEPTORS; ANTINOCICEPTION ID NALTRINDOLE 5'-ISOTHIOCYANATE; OPIATE RECEPTORS; ENKEPHALIN; MORPHINE; NALTREXONE; TOLERANCE; SUBTYPES; COMPLEX; LIGAND AB Several lines of data support the existence of two classes of delta receptors: the delta(cx)-binding site, which is the delta-binding site of the mu-delta opioid receptor complex, and the delta(ncx), which is the noncomplexed delta-receptor. [D-Ala2,Leu5,Cys6]Enkephalin (DALCE) is an extended analog of [Leu5]enkephalin, which has been shown to bind irreversibly to delta-receptors via the terminal cysteine by formation of a disulfide bond with the receptor. In vivo studies have shown that DALCE produces short-lived antinociceptive actions, followed by long-term antagonism of delta-receptor-mediated antinociception. The major goal of the present study was to examine the effect of DALCE on the delta(cx) and delta(ncx)-binding sites in vitro and in vivo. Intracerebroventricular administration of 40-mu-g DALCE failed to decrease [H-3][D-Ala2,D-Leu5]enkephalin binding to the delta(cx) and delta(ncx)-binding sites. Pretreatment of membranes with DALCE in vitro greatly reduced the B(max) of the delta(ncx)-binding site, without significantly altering the B(max) of the delta(cx)-binding site. These findings suggest that when administered in vivo, DALCE fails to distribute uniformly throughout the brain, and that it therefore binds covalently to opioid receptors mostly in the periventricular regions. Viewed collectively, these data support the hypothesis that DALCE acts as a selective delta(ncx)-antagonist, and that the delta(ncx) binding site, which is sensitive to DALCE, is most likely synonymous with the recently described delta-1 receptor. C1 NIDDK,MED CHEM,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT MED NEUROSCI,WASHINGTON,DC 20307. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL-AUG PY 1992 VL 13 IS 4 BP 691 EP 694 DI 10.1016/0196-9781(92)90174-2 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA JL834 UT WOS:A1992JL83400010 PM 1331996 ER PT J AU COY, DH MUNGAN, Z ROSSOWSKI, WJ CHENG, BL LIN, JT MROZINSKI, JE JENSEN, RT AF COY, DH MUNGAN, Z ROSSOWSKI, WJ CHENG, BL LIN, JT MROZINSKI, JE JENSEN, RT TI DEVELOPMENT OF A POTENT BOMBESIN RECEPTOR ANTAGONIST WITH PROLONGED INVIVO INHIBITORY ACTIVITY ON BOMBESIN-STIMULATED AMYLASE AND PROTEIN RELEASE IN THE RAT SO PEPTIDES LA English DT Article DE BOMBESIN ANTAGONISTS; BINDING; RAT ACINI; C6 CELLS; AMYLASE RELEASE ID SWISS 3T3 CELLS; ANTIMITOTIC ACTIVITY; PANCREATIC ACINAR; MUSCLE-CELLS; PEPTIDES; ANALOGS; SECRETION; SUBTYPES AB Of the various types of potent bombesin(Bn)/gastrin releasing peptide receptor antagonists that have been discovered, the desMet14-methyl ester peptides are devoid of residual agonist activity and are among the most potent in terms of in vitro receptor blockade and also in terms of their prolonged inhibition of bombesin-stimulated amylase and protein release in the mt. We have now examined the in vitro and in vivo properties of a new series of methyl ester analogues, [D-Phe6]Bn(6-13)OMe, [D-Phe6,D-Ala11]Bn(6-13)OMe, N(alpha)-propionyl-[D-Ala24]GRP(20-26)OMe, and [D-pentafluoro-Phe6,D-Ala11]Bn(6-13)OMe, which have an additional D-amino acid substituent and some highly lipophilic moieties at the N-terminus. All analogues were able to potently antagonize the ability of Bn to stimulate amylase release from rat acinar cells, with IC50 values of 2.4, 2.5, 0.6, and 1.3 nM, respectively. The four peptides were found to have binding affinities for these cells comparable to Bn itself, with K(i)s of 10.3, 2.8, 5.5, and 3.6 nM, respectively, but all had little or no affinity for neuromedin B receptors on murine C6 cells. Single bolus IV injections of these peptides were found to potently inhibit amylase and protein release caused by IV infusion of bombesin into the rat. Generally the peptides containing the D-Ala substituent were longer acting than [D-Phe 6]Bn(6-13)OMe, so that [D-PheD-Ala11]Bn(6-13)OMe and N(alpha)-propionyl-[D-Ala24]GRP(20-26)OMe displayed significant inhibitory effects for up to 1.5 h after administration. The most lipophilic analogue, [D-pentafluoro-Phe6,D-Ala11]Bn(6-13) OMe, however, was active for up to 4.5 h after injection and, at the same dose level as the other peptides, it had a fifteenfold longer duration of action. This analog appears to be a good candidate for clinical studies where prolonged blockade of endogenous bombesin-like peptides is desirable. C1 TULANE UNIV,MED CTR,DEPT MED,GASTROENTEROL SECT,NEW ORLEANS,LA 70112. NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP COY, DH (reprint author), TULANE UNIV,MED CTR,DEPT MED,PEPTIDE RES LABS,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. FU NCI NIH HHS [CA-45153] NR 34 TC 50 Z9 50 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL-AUG PY 1992 VL 13 IS 4 BP 775 EP 781 DI 10.1016/0196-9781(92)90186-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA JL834 UT WOS:A1992JL83400022 PM 1279632 ER PT J AU VISWANATHAN, M SAAVEDRA, JM AF VISWANATHAN, M SAAVEDRA, JM TI EXPRESSION OF ANGIOTENSIN-II AT(2) RECEPTORS IN THE RAT SKIN DURING EXPERIMENTAL WOUND-HEALING SO PEPTIDES LA English DT Article DE ANGIOTENSIN-II; AT(1) RECEPTORS; AT(2) RECEPTORS; SKIN; WOUND HEALING ID SUBTYPES; AUTORADIOGRAPHY; IDENTIFICATION; GROWTH AB We localized and characterized angiotensin II AT1 and AT2 receptors in the skin of 2-week-old rats during experimental wound healing. Both AT1 and AT2 were present in the skin. Three days after wounding, the expression of angiotensin II receptors was significantly enhanced in the dermis as well as in a localized band within the superficial dermis of the skin surrounding the wound. The major proportion of this increase was due to angiotensin II AT2 receptors. Our results suggest a physiological role for AT2 receptors in the process of tissue repair. RP VISWANATHAN, M (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,RM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 152 Z9 154 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL-AUG PY 1992 VL 13 IS 4 BP 783 EP 786 DI 10.1016/0196-9781(92)90187-8 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA JL834 UT WOS:A1992JL83400023 PM 1437716 ER PT J AU MERCHENTHALER, I MADERDRUT, JL OHARTE, F CONLON, JM AF MERCHENTHALER, I MADERDRUT, JL OHARTE, F CONLON, JM TI LOCALIZATION OF NEUROKININ-B IN THE CENTRAL-NERVOUS-SYSTEM OF THE RAT SO PEPTIDES LA English DT Article DE BRAIN; HYPOTHALAMUS; IMMUNOCYTOCHEMISTRY; NEUROKININ-B; PEPTIDES; RADIOIMMUNOASSAY; SUBSTANCE-P; TACHYKININS ID SUBSTANCE-P PRECURSOR; PORCINE SPINAL-CORD; MESSENGER-RNA; REGIONAL DISTRIBUTION; INSITU HYBRIDIZATION; NEUROMEDIN-K; IMMUNOCYTOCHEMICAL LOCALIZATION; TYROSINE-HYDROXYLASE; TISSUE DISTRIBUTION; PERIPHERAL-TISSUES AB The distribution of neurokinin B (NKB) was determined by immunocytochemistry with antisera directed toward its amino terminus. Immunoreactive perikarya were detected in the main and accessory olfactory bulbs, cortical regions, the olfactory tubercle, the bed nucleus of the stria terminalis, the diagonal band of Broca, the nucleus accumbens, the septum, the neostriatum, several hypothalamic nuclei, the superior colliculus, the central gray, the substantia nigra the medullary reticular formation, and the external cuneate nucleus. The distribution of NKB-containing perikarya revealed by immunocytochemistry was similar to the distribution of protachykinin B-containing cells previously by in situ hybridization. Immunoreactive nerve fibers and terminals were detected in all major subdivisions of the brain. The levels of NK.B measured by radioimmunoassay were highest in the hypothalamus. The distribution of NKB in the rat brain was similar to the distribution of substance P; however, there were several regions where the two distributions were clearly different. C1 CREIGHTON UNIV,COLL MED,DIV BIOCHEM,DEPT BIOMED SCI,OMAHA,NE 68178. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,MD C4-07,RES TRIANGLE PK,NC 27709, USA. OI Conlon, John Michael/0000-0002-4343-1551 NR 57 TC 60 Z9 63 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL-AUG PY 1992 VL 13 IS 4 BP 815 EP 829 DI 10.1016/0196-9781(92)90192-6 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA JL834 UT WOS:A1992JL83400028 PM 1437720 ER PT J AU HIENZ, RD TURKKAN, JS SPEAR, DJ SANNERUD, CA KAMINSKI, BJ ALLEN, RP AF HIENZ, RD TURKKAN, JS SPEAR, DJ SANNERUD, CA KAMINSKI, BJ ALLEN, RP TI GENERAL ACTIVITY IN BABOONS MEASURED WITH A COMPUTERIZED, LIGHTWEIGHT PIEZOELECTRIC MOTION SENSOR - EFFECTS OF DRUGS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE MOTOR ACTIVITY; DRUGS; D-AMPHETAMINE; COCAINE; DELTA-9 THC; VERAPAMIL; HYDROCHLOROTHIAZIDE; BABOON; NONHUMAN PRIMATES AB A small, 1-oz activity-monitoring device is described for measuring motor activity continuously for periods of up to 42 days. The monitor employs a piezoelectric sensor that detects extremely small accelerations induced by movements. The monitor can be placed on collars or harnesses (e.g., for rabbits, cats, dogs, nonhuman primates, etc.). The use of the monitor is described within numerous laboratories studying the behavioral pharmacology of drugs in individually caged laboratory baboons. Patterns of daily activity were reliably recorded over periods of several months, and reflected the normal activity patterns of animals. The activity monitor recorded reliable, drug-induced changes in general activity that paralleled the known effects of the same drugs on learned behaviors. Low doses of the stimulants cocaine and d-amphetamine both increased general activity. Marked reductions in general activity were observed following both the administration of DELTA-9-tetrahydrocannabinol and an antihypertensive drug combination of diuretic and verapamil. C1 NIDR,ADDICT RES CTR,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,CTR HEARING SCI,BALTIMORE,MD 21224. FRANCIS SCOTT KEY MED CTR,SLEEP DISORDERS CLIN,BALTIMORE,MD 21224. RP HIENZ, RD (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,DIV BEHAV BIOL,BEHAV BIOL RES CTR,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA 01147, DA 02490, DA 04731] NR 31 TC 7 Z9 8 U1 4 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1992 VL 42 IS 3 BP 497 EP 507 DI 10.1016/0091-3057(92)90145-6 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JA636 UT WOS:A1992JA63600016 PM 1329115 ER PT J AU VANGIERSBERGEN, PLM PALKOVITS, M DEJONG, W AF VANGIERSBERGEN, PLM PALKOVITS, M DEJONG, W TI INVOLVEMENT OF NEUROTRANSMITTERS IN THE NUCLEUS-TRACTUS-SOLITARII IN CARDIOVASCULAR REGULATION SO PHYSIOLOGICAL REVIEWS LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; THYROTROPIN-RELEASING-HORMONE; RAT MEDULLA-OBLONGATA; LOWER BRAIN-STEM; SPONTANEOUSLY-HYPERTENSIVE RATS; DORSAL VAGAL COMPLEX; GAMMA-AMINOBUTYRIC ACID; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; NEUROPEPTIDE-Y (NPY)-LIKE; GENE-RELATED PEPTIDE C1 STRASBOURG CTR,STRASBOURG,FRANCE. SEMMELWEIS UNIV MED,DEPT ANAT,H-1085 BUDAPEST 8,HUNGARY. UNIV CINCINNATI,COLL MED,DEPT PHARMACOL & CELL BIOPHYS,CINCINNATI,OH 45221. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP VANGIERSBERGEN, PLM (reprint author), MERRELL DOW PHARMACEUT INC,RES INST,CINCINNATI,OH 45215, USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 447 TC 226 Z9 228 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JUL PY 1992 VL 72 IS 3 BP 789 EP 824 PG 36 WC Physiology SC Physiology GA JC867 UT WOS:A1992JC86700006 PM 1352638 ER PT J AU GORZIGLIA, MI COLLINS, PL AF GORZIGLIA, MI COLLINS, PL TI INTRACELLULAR AMPLIFICATION AND EXPRESSION OF A SYNTHETIC ANALOG OF ROTAVIRUS GENOMIC RNA BEARING A FOREIGN MARKER GENE - MAPPING CIS-ACTING NUCLEOTIDES IN THE 3'-NONCODING REGION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RNA TRANSFECTION; VIRAL PROMOTER MAPPING; MUTAGENESIS; INTERSEROTYPE COMPLEMENTATION ID DOUBLE-STRANDED-RNA; CELLS AB cDNAs were constructed to encode plus- or minus-sense analogs of gene 9 RNA of porcine rotavirus strain OSU in which the bacterial chloramphenicol acetyltransferase (CAT) reporter gene was flanked by the 5'-terminal 44 nucleotides (nt) and 3'-terminal 35 nt of the authentic rotavirus gene. Transfection of plus-sense gene-9-CAT RNA into rotavirus-infected cells resulted in its amplification and in the efficient expression of CAT; this was greatly enhanced by the presence of a 5' cap structure. Amplification was ablated by omitting the rotavirus superinfection or by removing- the 3'-terminal 35-nt rotavirus sequence from the RNA. This result indicated that amplification depended both on rotavirus proteins supplied in trans and on cis-acting rotavirus sequences. Minus-sense or double-stranded gene-9-CAT RNA was essentially inactive, indicating that synthetic RNAs can be introduced into the rotavirus replicative cycle in vivo only when provided in the plus sense. However, incorporation of the CAT-bearing RNA into infectious rotavirus was not detected. Two heterologous rotaviruses, the simian RRV and chicken Ch2 strains, efficiently complemented the OSU-based gene-9-CAT RNA, even though the Ch2 strain was only 50%-66% related in the noncoding regions. Mutational analysis of the 35-nt 3'-noncoding region showed that the 3'-terminal 12 or 17 nt were sufficient for reduced (12% or 23%, respectively) levels of amplification, whereas inclusion of the 3'-terminal 19 nt fully restored amplification. Thus, the 3'-terminal cis-acting signals required for amplification include the 7-nt-terminal consensus sequence together with 12 nt of adjoining, less-well-conserved sequence. RP GORZIGLIA, MI (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,BETHESDA,MD 20892, USA. NR 17 TC 23 Z9 24 U1 1 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1992 VL 89 IS 13 BP 5784 EP 5788 DI 10.1073/pnas.89.13.5784 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC868 UT WOS:A1992JC86800018 PM 1321421 ER PT J AU YOU, M WANG, YA STONER, G YOU, LA MARONPOT, R REYNOLDS, SH ANDERSON, M AF YOU, M WANG, YA STONER, G YOU, LA MARONPOT, R REYNOLDS, SH ANDERSON, M TI PARENTAL BIAS OF KI-RAS ONCOGENES DETECTED IN LUNG-TUMORS FROM MOUSE HYBRIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CARCINOGENESIS; GENETIC SUSCEPTIBILITY ID MICE; SUSCEPTIBILITY; GENE; ACTIVATION; CELLS; DNA; PROTOONCOGENE; AMPLIFICATION; POLYMERASE; SEQUENCES AB A mouse strain with low, lung tumor susceptibility (C3H) and a strain with high lung tumor susceptibility (A/J) were reciprocally crossed to produce C3A and AC3 F1 hybrid mice. Ki-ras oncogenes were detected in spontaneous and chemically induced lung tumors obtained from the C3A and AC3 mice. To further explore the genetics of the Ki-ras gene in mouse lung tumor susceptibility, the parental origin of Ki-ras oncogenes detected in lung tumors from the F1 hybrids was determined by a strategy based on a 37-base-pair deletion in the second intron of the A/J Ki-ras allele. Ki-ras oncogenes were derived from the A/J parent in 38 of 40 tumors obtained from C3A mice and 30 of 30 tumors from AC3 mice. The observation that the activated oncogene in hybrids originates from the susceptible parent suggests that the Ki-ras gene is directly linked to mouse lung tumor susceptibility. This finding may have implications for pulmonary adenocarcinoma development in humans, since Ki-ras oncogenes are detected in 35% of this human tumor type. C1 NIEHS,RES TRIANGLE PK,NC 27709. MED COLL OHIO,TOLEDO,OH 43699. NR 26 TC 101 Z9 102 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1992 VL 89 IS 13 BP 5804 EP 5808 DI 10.1073/pnas.89.13.5804 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC868 UT WOS:A1992JC86800022 PM 1352876 ER PT J AU FRIEDMAN, JM VITALE, M MAIMON, J ISRAEL, MA HOROWITZ, ME SCHNEIDER, BS AF FRIEDMAN, JM VITALE, M MAIMON, J ISRAEL, MA HOROWITZ, ME SCHNEIDER, BS TI EXPRESSION OF THE CHOLECYSTOKININ GENE IN PEDIATRIC TUMORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ECTOPIC HORMONE PRODUCTION; SMALL-ROUND-CELL TUMORS; NEUROEPITHELIOMA; EWING SARCOMA; NEUROPEPTIDES ID TERMINAL FLANKING PEPTIDE; CELL-LINES; EWINGS-SARCOMA; PERIPHERAL NEUROEPITHELIOMA; NERVOUS-SYSTEM; PIG BRAIN; RAT-BRAIN; ESTABLISHMENT; OCTAPEPTIDE; VERTEBRATE AB We have examined a wide range of cultured human tumor cell lines and found that a specific subset of tumors expresses the cholecystokinin (CCK) gene. All neuroepitheliomas (eight) and Ewing sarcoma (eight) cell lines that were tested express CCK RNA. In addition, two of six rhabdomyosarcoma cell lines also express the CCK gene, suggesting that rhabdomyosarcomas are probably heterogenous and that a subset may be similar to Ewing sarcoma and neuroepithelioma. Very few of the positive tumors express completely processed immunoreactive CCK. However, we have used a radioimmunoassay that detects the CCK precursor to demonstrate synthesis of CCK precursor-like peptides by all of the Ewing sarcoma and neuroepithelioma lines that were tested and by the rhabdomyosarcoma cell line that expresses CCK mRNA. These data demonstrate a consistent association of CCK gene expression with a specific group of human neoplasms. The data also add credence to the theory that Ewing sarcoma and neuroepithelioma are derived from the same transformed cell type. Finally, our results suggest that CCK gene expression may serve as a marker to distinguish these tumors, which are considered to be small-round-cell tumors of childhood, from other pediatric tumors. C1 LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT MED,DIV ENDOCRINOL & METAB,NEW HYDE PK,NY 11042. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. ROCKEFELLER UNIV,MOLEC BIOL LAB,NEW YORK,NY 10021. NCI,DIV CANC THERAPEUT PEDIAT BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,BRAIN TUMOR RES CTR,SAN FRANCISCO,CA 94143. RI Vitale, Maria/J-7277-2016 OI Vitale, Maria/0000-0003-2084-2718 FU NIMH NIH HHS [MH41960-03] NR 46 TC 14 Z9 15 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1992 VL 89 IS 13 BP 5819 EP 5823 DI 10.1073/pnas.89.13.5819 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC868 UT WOS:A1992JC86800025 PM 1631063 ER PT J AU COULTER, S RODBELL, M AF COULTER, S RODBELL, M TI HETEROTRIMERIC G-PROTEINS IN SYNAPTONEUROSOME MEMBRANES ARE CROSS-LINKED BY PARA-PHENYLENEDIMALEIMIDE, YIELDING STRUCTURES COMPARABLE IN SIZE TO CROSS-LINKED TUBULIN AND F-ACTIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; BIOPOLYMERS; GUANINE NUCLEOTIDE-BINDING PROTEIN ID REGULATORY PROTEINS; CGMP PHOSPHODIESTERASE; GUANINE-NUCLEOTIDES; SIGNAL TRANSDUCTION; GLUCAGON RECEPTOR; BINDING; ACTIVATION; COMPLEXES; RHODOPSIN; SUBUNITS AB We have treated rat brain synaptoneurosomes with the crosslinking agent N,N'-1,4-phenylenedimaleimide under conditions that cause extensive crosslinking of tubulin, F-actin, and the alpha and beta-subunits of three major types of heterotrimeric GTP-binding regulatory proteins (G(o), G(s), G(i)) present in brain membranes. The major crosslinked products are coeluted from Bio-Gel sizing columns as very large structures that do not penetrate stacking gels during SDS/PAGE. The alpha-subunits but not the beta-subunits of G(s), G(o), and G(i) also yield crosslinked products of intermediate sizes. None of the products are as small as the heterotrimeric G proteins extracted from brain by cholate or Lubrol. However, the large and intermediate crosslinked structures are strikingly similar to the large, polydisperse structures of the alpha-subunits of G(s), G(i), and G(o) extracted from synaptoneurosomes by the detergent octyl glucoside, which have sedimentation properties of multimeric proteins. Several ways in which multimeric forms of G proteins can explain the dynamic and pleiotropic actions of hormones and GTP on signal-transducing systems are discussed. RP NIEHS, CELLULAR & MOLEC PHARMACOL LAB, SIGNAL TRANSDUCT SECT, RES TRIANGLE PK, NC 27709 USA. OI Coulter, Sherry/0000-0002-2732-3470 NR 32 TC 40 Z9 40 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1992 VL 89 IS 13 BP 5842 EP 5846 DI 10.1073/pnas.89.13.5842 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC868 UT WOS:A1992JC86800030 PM 1631066 ER PT J AU BATRA, JK KASPRZYK, PG BIRD, RE PASTAN, I KING, CR AF BATRA, JK KASPRZYK, PG BIRD, RE PASTAN, I KING, CR TI RECOMBINANT ANTI-ERBB2 IMMUNOTOXINS CONTAINING PSEUDOMONAS EXOTOXIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHEMOTHERAPY; MONOCLONAL ANTIBODIES; GROWTH FACTOR RECEPTORS ID ESCHERICHIA-COLI; PROTO-ONCOGENE; RECEPTOR; BREAST; EXPRESSION; DOMAINS; CANCER; GENE AB Immunotoxins were made using five different murine monoclonal antibodies to the human erbB2 gene product and LysPE40, a 40-kDa recombinant form of Pseudomonas exotoxin (PE) lacking its cell-binding domain. All five conjugates were specifically cytotoxic to cancer cell lines overexpressing erbB2 protein. The most active conjugate was e23LysPE40, generated by chemical crosslinking of anti-erbB2 monoclonal antibody e23 to LysPE40. In addition, a recombinant immunotoxin, e23(Fv)PE40, was constructed that consists of the light-chain variable domain of e23 connected through a peptide linker to its heavy-chain variable domain, which in turn is fused to PE40. The recombinant protein was made in Escherichia coli, purified to near homogeneity, and shown to selectively kill cells expressing the erbB2 protooncogene. To improve the cytotoxic activity of e23(Fv)PE40, PE40 was replaced with a variant, PE38KDEL, in which the carboxyl end of PE is changed from Arg-Glu-Asp-Leu-Lys to Lys-Asp-Glu-Leu and amino acids 365-380 of PE are deleted. The e23(Fv)PE38KDEL protein inhibits the growth of tumors formed by the human gastric cancer cell line N87 in immunodeficient mice. C1 MOLEC ONCOL INC,19 FIRSTFIELD RD,GAITHERSBURG,MD 20878. NCI,DIV CANC BIOL DIAG & CENTERS,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 24 TC 134 Z9 141 U1 1 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1992 VL 89 IS 13 BP 5867 EP 5871 DI 10.1073/pnas.89.13.5867 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC868 UT WOS:A1992JC86800035 PM 1352878 ER PT J AU INSEL, TR SHAPIRO, LE AF INSEL, TR SHAPIRO, LE TI OXYTOCIN RECEPTOR DISTRIBUTION REFLECTS SOCIAL-ORGANIZATION IN MONOGAMOUS AND POLYGAMOUS VOLES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MICROTINE; AFFILIATION; PARENTAL BEHAVIOR; AMYGDALA; SEPTUM ID MICROTUS-OCHROGASTER; MATERNAL-BEHAVIOR; PRAIRIE VOLES; FEMALE RATS; AFFILIATIVE BEHAVIOR; SEXUAL-BEHAVIOR; BRAIN; AUTORADIOGRAPHY; PENNSYLVANICUS; PINETORUM AB The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor expression in brain. By in vitro receptor autoradiography with an iodinated oxytocin analogue, specific binding to brain oxytocin receptors was observed in both the monogamous prairie vole (Microtus ochrogaster) and the polygamous montane vole (Microtus montanus). In the prairie vole, oxytocin receptor density was highest in the prelimbic cortex, bed nucleus of the stria terminalis, nucleus accumbens, midline nuclei of the thalamus, and the lateral aspects of the amygdala. These brain areas showed little binding in the montane vole, in which oxytocin receptors were localized to the lateral septum, ventromedial nucleus of the hypothalamus, and cortical nucleus of the amygdala. Similar differences in brain oxytocin receptor distribution were observed in two additional species, the monogamous pine vole (Microtus pinetorum) and the polygamous meadow vole (Microtus pennsylvanicus). Receptor distributions for two other neurotransmitter systems implicated in the mediation of social behavior, benzodiazepines, and mu-opioids did not show comparable species differences. Furthermore, in the montane vole, which shows little affiliative behavior except during the postpartum period, brain oxytocin receptor distribution changed within 24 hr of parturition, concurrent with the onset of maternal behavior. We suggest that variable expression of the oxytocin receptor in brain may be an important mechanism in evolution of species-typical differences in social bonding and affiliative behavior. RP INSEL, TR (reprint author), NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 54 TC 414 Z9 419 U1 5 U2 66 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 1992 VL 89 IS 13 BP 5981 EP 5985 DI 10.1073/pnas.89.13.5981 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JC868 UT WOS:A1992JC86800058 PM 1321430 ER PT J AU GLOWA, JR STERNBERG, EM GOLD, PW AF GLOWA, JR STERNBERG, EM GOLD, PW TI DIFFERENTIAL BEHAVIORAL-RESPONSE IN LEW/N AND F344/N RATS - EFFECTS OF CORTICOTROPIN RELEASING HORMONE SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE AUTOIMMUNE DISEASE; BEHAVIOR; CORTICOTROPIN RELEASING HORMONE; RAT STRAINS; STRESS ID WALL-INDUCED ARTHRITIS; BIOCHEMICAL MANIFESTATIONS; NERVOUS-SYSTEM; LEWIS RATS; INTERLEUKIN-1; SECRETION; NEUROBIOLOGY; DEPRESSION; STRESS AB 1. Previous studies have documented that LEW/N rats exhibit an inflammatory response when challenged with a variety of stressful stimuli while histocompatible F344/N rats do not. These differences are thought to be regulated by the HPA axis. 2. In order to examine behavioral correlates of suspected differences in HPA activity in these strains, the baseline response to an open field as well as the effects of 3-mu-g/rat of CRH i.c.v. were compared across strains. 3. Significant differences in the pattern of activity in the open field, rearing, and grooming, as well as effects of CRH were found between strains. 4. The differences found are consistent with the notion that differences in endogenous CRH may form the basis for the differential susceptibility of these strains to autoimmune disease, and provide a model to study genetic determinants of CNS-immune system interactions. RP GLOWA, JR (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BIOPSYCHOL UNIT,BLDG 14D,RM 311,BETHESDA,MD 20892, USA. NR 29 TC 43 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL PY 1992 VL 16 IS 4 BP 549 EP 560 DI 10.1016/0278-5846(92)90060-R PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HY865 UT WOS:A1992HY86500010 PM 1641498 ER PT J AU SUGUNA, K PADLAN, EA BOTT, R BOGER, J PARRIS, KD DAVIES, DR AF SUGUNA, K PADLAN, EA BOTT, R BOGER, J PARRIS, KD DAVIES, DR TI STRUCTURES OF COMPLEXES OF RHIZOPUSPEPSIN WITH PEPSTATIN AND OTHER STATINE-CONTAINING INHIBITORS SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE ASPARTIC PROTEINASE; RENIN INHIBITORS; X-RAY DIFFRACTION ID LEAST-SQUARES REFINEMENT; ASPARTIC PROTEINASE; X-RAY; MACROMOLECULAR STRUCTURES; BINDING; RESOLUTION; CHINENSIS; PROTEASE; PENICILLOPEPSIN; MECHANISM AB The three-dimensional structures of the complexes of the aspartic proteinase from Rhizopus chinensis (Rhizopuspepsin, EC 3.4.23.6) with pepstatin and two pepstatin-like peptide inhibitors of renin have been determined by X-ray diffraction methods and refined by restrained least-squares procedures. The inhibitors adopt an extended conformation and lie in the deep groove located between the two domains of the enzyme. Inhibitor binding is accompanied by a conformational change at the "flap," a beta-hairpin loop region, that projects over the binding cleft and closes down over the inhibitor, excluding water molecules from the vicinity of the scissile bond. The hydroxyl group of the central statyl residue of the inhibitors replaces the water molecule found between the two active aspartates, Asp-35 and Asp-218, in the native structure. The refined structures provide additional data to define the specific subsites of the enzyme and also show a system of hydrogen bonding to the inhibitor backbone similar to that observed for a reduced inhibitor. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 49 TC 37 Z9 37 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD JUL PY 1992 VL 13 IS 3 BP 195 EP 205 DI 10.1002/prot.340130303 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HU487 UT WOS:A1992HU48700002 PM 1603809 ER PT J AU PANLILIO, LV WEISS, SJ THOMAS, DA GLOWA, JR AF PANLILIO, LV WEISS, SJ THOMAS, DA GLOWA, JR TI FG-7142 SELECTIVELY DECREASES NONPUNISHED RESPONDING, BUT HAS NO ANXIOGENIC EFFECTS ON TIME ALLOCATION IN A CONFLICT SCHEDULE SO PSYCHOPHARMACOLOGY LA English DT Article DE CONFLICT SCHEDULE; FG-7142; INVERSE AGONIST; PUNISHMENT; RAT ID BENZODIAZEPINE; RATS; CHLORDIAZEPOXIDE; RO-15-1788; FLUMAZENIL; ENHANCE; DRUGS AB Previous work (Thomas et al. 1990) showed that an anxiolytic benzodiazepine increased the time allocated to responding in a conflict situation (where responses were both food-reinforced and shock-punished) versus a nonpunishment situation. The present experiment tested whether a benzodiazepine-receptor inverse agonist (FG 7142, 1-30 mg/kg) would have the opposite effect (i.e., decrease time spent responding in a punishment situation). Chain pulls determined whether a rat's lever presses were reinforced on 1) a lean variable-interval schedule, or 2) a richer variable-interval schedule in which responding also produced shock intermittently. FG 7142 dose-dependently decreased nonpunished lever responding, but did not affect punished responding. The drug nonselectively decreased chain pulling (the schedule-switching response). Like chlordiazepoxide, FG 7142 increased the time spent in the punishment component, showing that not all effects of benzodiazepine-receptor agonists and inverse agonists are opposite. These results are inconsistent with expectations that anxiogenic actions of FG 7142 should 1) decrease punished responding; 2) increase the rate of responses that terminate the punishment condition; and 3) decrease time spent in the punishment component. Rather, nonsuppressed responding seems most sensitive to decreases by FG 7142. C1 NIDR,NEUROBIOL & ANESTHESIOL,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BIOPSYCHOL UNIT,BETHESDA,MD 20892. RP PANLILIO, LV (reprint author), AMERICAN UNIV,DEPT PSYCHOL,WASHINGTON,DC 20016, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1992 VL 108 IS 1-2 BP 185 EP 188 DI 10.1007/BF02245305 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HZ555 UT WOS:A1992HZ55500029 PM 1329131 ER PT J AU KAHN, RS KLING, MA WETZLER, S ASNIS, GM VANPRAAG, H AF KAHN, RS KLING, MA WETZLER, S ASNIS, GM VANPRAAG, H TI EFFECT OF M-CHLOROPHENYLPIPERAZINE ON PLASMA ARGININE-VASOPRESSIN CONCENTRATIONS IN HEALTHY-SUBJECTS SO PSYCHOPHARMACOLOGY LA English DT Article DE SEROTONIN; ARGININE-VASOPRESSIN; M-CHLOROPHENYLPIPERAZINE; HUMAN ID PHARMACOLOGICAL CHARACTERIZATION; SEROTONIN RECEPTORS; PROLACTIN SECRETION; NEURO-ENDOCRINE; ACTIVATION; RATS; STIMULATION; AGONIST; BASAL AB It has been demonstrated convincingly that ACTH and prolactin release are under the stimulatory control of serotonin (5-hydroxytryptamine, 5HT). Recent animal studies suggest that stimulation of 5HT activity also induces the release of arginine-vasopressin (AVP). More specifically, m-chlorophenylpiperazine (MCPP), a 5HT agonist widely used to examine 5HT receptor responsivity in human subjects, has been found to induce AVP release in rodents. This study examined whether MCPP increased plasma AVP levels in healthy human subjects. MCPP was administered orally to 17 healthy subjects in a placebo-controlled design in doses of 0.25 and 0.5 mg/kg. AVP was measured twice hourly over a 210 min period after administration of capsules. MCPP did not significantly alter AVP levels as compared to placebo. However, female subjects had significantly lower plasma AVP levels than males. Since it has been suggested that MCPP-induced AVP release in animals is due to stimulation of 5HT1c receptors, the fact that MCPP did not induce the release of AVP in humans suggests that either MCPP is not a potent 5HT1c agonist or that AVP is not released by stimulation of 5HT(1c) receptors in human subjects. The observation of gender differences in plasma AVP levels suggests that this factor should be taken into account in future studies of AVP secretion in plasma. C1 VET ADM MED CTR,BRONX,NY 10468. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,DEPT PSYCHIAT,BRONX,NY 10467. RP KAHN, RS (reprint author), MT SINAI HOSP,SCH MED,DEPT PSYCHIAT,140 W KINGSBRIDGE RD,BRONX,NY 10468, USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 24 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 1992 VL 108 IS 1-2 BP 225 EP 228 DI 10.1007/BF02245312 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HZ555 UT WOS:A1992HZ55500036 PM 1410142 ER PT J AU SRIVASTAVA, S SMART, C MARCINIAK, TA DERRICK, L AF SRIVASTAVA, S SMART, C MARCINIAK, TA DERRICK, L TI ACCESSING NCIS SEER CANCER DATA-BASE WITH SEERQUERY AND CD-ROM SO PUBLIC HEALTH REPORTS LA English DT Article AB The National Cancer Institute operates the Surveillance, Epidemiology, and End Results (SEER) cancer data base. SEER data are obtained from participating population-based registries that monitor cancer incidence and patient survival in a representative 10 percent sample of the general population. The data cover all cancers (except superficial skin cancers) in the defined regional populations. SeerQuery is a personal computer program for accessing that data on IBM-compatible personal computer compact diskettes in read-only memory (CD-ROM) form. SeerQuery facilitates rapid access to cancer data at minimal cost and effort to the user. SeerQuery is menu-driven, enabling physicians and other health care professionals to query the data base directly. They can use the data to determine cancer frequency, perform cross-tabulation, determine incidence, and calculate survival using such variables as primary cancer site, histologic type, stage, sex, age, and race. The comprehensive data base lacks many selection biases that are inherent in data reported from other sources. SeerQuery has applications in professional education and in cancer control program planning and resource allocation. C1 NCI,COMP SYST BRANCH,BETHESDA,MD 20892. UNIV UTAH,ROCKY MT CANC DATA SYST,SALT LAKE CITY,UT 84112. RP SRIVASTAVA, S (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1992 VL 107 IS 4 BP 397 EP 401 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JH966 UT WOS:A1992JH96600004 PM 1641435 ER PT J AU ROGOT, E SORLIE, PD JOHNSON, NJ AF ROGOT, E SORLIE, PD JOHNSON, NJ TI LIFE EXPECTANCY BY EMPLOYMENT STATUS, INCOME, AND EDUCATION IN THE NATIONAL LONGITUDINAL MORTALITY STUDY SO PUBLIC HEALTH REPORTS LA English DT Article ID CENSUS SAMPLES; DEATH-INDEX AB Based on data from the National Longitudinal Mortality Study for 1979-85, life expectancies are estimated for white men and white women by education, by family income, and by employment status. Life expectancy varies directly with amount of schooling and with family income. Differences in life expectancy at age 25 between the highest and the lowest levels of education completed were about 6 years for white men and about 5 years for white women. For family income, differences between the highest and the lowest income groups were about 10 years for white men and 4.3 years for white women. The largest differences in life expectancy were between employment categories. At age 25, white men in the labor force lived on average about 12 more years than those not in the labor force, and white women lived on average about 9 more years. For those who were unable to work compared with those in the labor force, the difference for white men was about 20 years; for white women, 29 years. Results in this study showed much the same differentials in life expectancy for education as the earlier Kitagawa-Hauser study. C1 US BUR CENSUS,DIV STAT METHODS,WASHINGTON,DC 20233. RP ROGOT, E (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,FED BLDG,ROOM 2C08,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 11 TC 90 Z9 91 U1 0 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1992 VL 107 IS 4 BP 457 EP 461 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JH966 UT WOS:A1992JH96600012 PM 1641443 ER PT J AU CHOYKE, PL AF CHOYKE, PL TI THE UROGRAM - ARE RUMORS OF ITS DEATH PREMATURE SO RADIOLOGY LA English DT Article DE DEVILS ADVOCATE; GENITOURINARY SYSTEM, US; URETER, CALCULI; UROGRAPHY ID CALCULI; MANAGEMENT C1 GEORGETOWN UNIV MED CTR,DEPT RADIOL,WASHINGTON,DC. RP CHOYKE, PL (reprint author), NIH,DEPT RADIOL,BLDG 10,RM 1C660,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 23 Z9 23 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1992 VL 184 IS 1 BP 33 EP 36 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HZ682 UT WOS:A1992HZ68200006 PM 1609097 ER PT J AU DOPPMAN, JL PASS, HI NIEMAN, LK MILLER, DL CHANG, R CUTLER, GB CHROUSOS, GP JAFFE, GS NORTON, JA AF DOPPMAN, JL PASS, HI NIEMAN, LK MILLER, DL CHANG, R CUTLER, GB CHROUSOS, GP JAFFE, GS NORTON, JA TI CORTICOTROPIN-SECRETING CARCINOID-TUMORS OF THE THYMUS - DIAGNOSTIC UNRELIABILITY OF THYMIC VENOUS SAMPLING SO RADIOLOGY LA English DT Article DE CUSHING SYNDROME; HORMONES, ECTOPIC; THYMUS, NEOPLASMS; VEINS, BLOOD SAMPLING ID CUSHINGS-SYNDROME; PULMONARY AB Three patients with Cushing syndrome due to ectopic production of corticotropin underwent total thymectomy on the basis of elevated concentrations of corticotropin in selective samples from thymic veins but in the absence of a radiographically detectible thymic mass. In one patient, radiologic examination demonstrated hyperplasia of neuroendocrine cells staining positively for corticotropin throughout the thymus but no discrete mass. This patient had complete remission after total thymectomy. The other two patients had no evidence of an intrathymic source of corticotropin, and both had persistent Cushing syndrome. Elevated levels of corticotropin in thymic vein samples may reflect corticotropin production by pulmonary bronchial carcinoid tumors, mediastinal metastases, thymic carcinoids, or diffuse hyperplasia of intrathymic neuroendocrine elements. In the absence of a demonstrable intrathymic mass, corticotropin gradients in thymic veins do not reliably indicate a thymic source of corticotropin and should not necessarily be used as a basis for exploratory thoracotomy or blind thymectomy. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NCI,DIV CANC BIOL,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. RP DOPPMAN, JL (reprint author), NCI,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 15 TC 23 Z9 23 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1992 VL 184 IS 1 BP 71 EP 74 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HZ682 UT WOS:A1992HZ68200016 PM 1319078 ER PT J AU WILSKE, B BARBOUR, AG BERGSTROM, S BURMAN, N RESTREPO, BI ROSA, PA SCHWAN, T SOUTSCHEK, E WALLICH, R AF WILSKE, B BARBOUR, AG BERGSTROM, S BURMAN, N RESTREPO, BI ROSA, PA SCHWAN, T SOUTSCHEK, E WALLICH, R TI ANTIGENIC VARIATION AND STRAIN HETEROGENEITY IN BORRELIA SPP SO RESEARCH IN MICROBIOLOGY LA English DT Article DE BORRELIA, ANTIGENICITY; ANTIGENIC VARIATION AND HETEROGENEITY, RECOMBINANT PROTEINS, VACCINATION ID LYME-DISEASE SPIROCHETE; IMMUNOGLOBULIN-G RESPONSE; VARIABLE MAJOR PROTEINS; OUTER SURFACE PROTEIN; BURGDORFERI STRAINS; IMMUNOLOGICAL ANALYSIS; MONOCLONAL-ANTIBODY; INVITRO CULTIVATION; MOLECULAR ANALYSIS; NORTH-AMERICAN AB Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In relapsing fever, new borrelia serotypes emerge at a high rate spontaneously, a mechanism that is caused by DNA rearrangements on linear plasmid translocating genes coding for variable major proteins from previous silent to expression sites (i.e. from inner sites to telomeric sites of the plasmid). As a result of this variation, the borreliae escape the immune response of the host, thus leading to the relapse phenomenon. In B. burgdorferi, which is the causative agent of the multisystem disorder Lyme borreliosis, there is also a growing body of findings that antigenic variation is involved in pathogenesis of the disease. Phenotypic variation of strains in vitro concerns the size and the amount of surface-associated proteins (OspA, OspB and pC). There are indications that OspA and OspB truncations are due to deletions within the ospAB operon caused by recombination events, and that OspA/OspB-less mutants lack the 49-kb plasmid that bears the ospAB operon. With the increasing number of isolates obtained from various geographic and biological sources, it became apparent that B. burgdorferi is immunologically and genetically more heterogeneous, as previously believed. The major outer surface proteins OspA and OspB (which have been efficient antigens in vaccine studies) are heterogeneous at a genetic level. The same degree of genetic non-identity was observed for the pC protein. Other proteins like flagellin and the highly specific immunodominant p100 range protein show a lower degree of non-identity. Recombinant OspA, pC, p100 range protein and flagellin have been hyperexpressed in E. coli and these proteins are immunologically reactive. This allows further research for development of vaccines and diagnostic tools. B. burgdorferi isolates have been investigated with genotyping (DNA hybridization, PCR and 16S rRNA analysis) as well as serotyping by various authors. Comparison of the different methods has shown good agreement when the same strains have been investigated. No correlation could be found between different phenotypic and genotypic groups with respect to the ability to cause arthritis in SCID mice. A serotyping system based on immunological differences in OspA detected by a panel of monoclonal antibodies has been proposed. Serotyping a large number of B. burgdorferi isolates has shown a striking predominance of the OspA serotype 2 among European isolates from human skin, in contrast to isolates from ticks or CSF. Genetic and immunological diversity among B. burgdorferi strains and immunodominant proteins (including respective recombinant proteins) of these strains raises many questions in the development of vaccines as well as diagnostic antigens, DNA probes and PCR primers. However, the knowledge of conserved and variable regions among the different protein-encoding genes of B. burgdorferi may help to develop efficient diagnostic reagents and vaccines. C1 UMEA UNIV, DEPT MICROBIOL, S-90187 UMEA, SWEDEN. NIH, ROCKY MT LABS, HAMILTON, MT 59840 USA. MIKROGEN GMBH, W-8000 MUNICH 2, GERMANY. GERMAN CANC RES CTR, DEPT APPL IMMUNOL, W-6900 HEIDELBERG, GERMANY. UNIV TEXAS, HLTH SCI CTR, DEPT MICROBIOL, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. RP WILSKE, B (reprint author), UNIV MUNICH, MAX VON PETTENKOFER INST HYG & MED MIKROBIOL, PETTENKOFER STR 9A, W-8000 MUNICH 2, GERMANY. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 NR 61 TC 81 Z9 82 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0923-2508 EI 1769-7123 J9 RES MICROBIOL JI Res. Microbiol. PD JUL-AUG PY 1992 VL 143 IS 6 BP 583 EP 596 DI 10.1016/0923-2508(92)90116-6 PG 14 WC Microbiology SC Microbiology GA JM117 UT WOS:A1992JM11700006 PM 1475519 ER PT J AU BERGSTROM, S GARON, CF BARBOUR, AG MACDOUGALL, J AF BERGSTROM, S GARON, CF BARBOUR, AG MACDOUGALL, J TI EXTRACHROMOSOMAL ELEMENTS OF SPIROCHETES SO RESEARCH IN MICROBIOLOGY LA English DT Article; Proceedings Paper CT 1ST INTERNATIONAL MEETING ON THE MOLECULAR BIOLOGY OF SPIROCHETES CY OCT 21-23, 1991 CL ANNECY, FRANCE SP MARDX DIAGNOST, MEDIMMUNE & SPECIALTY LABS, FDN MARCEL MERIEUX, ABBOTT LABS, BIOCHIM, CONNAUGHT LABS, FT DODGE LABS, HOECHST ROUSSEL DE CHROMOSOME, SPIROCHETE, VIRULENCE, PLASMID; MINICHROMOSOME, MAXICHROMOSOME, GENETIC CAPACITY, LINEAR REPLICONS ID BACTERIUM BORRELIA-BURGDORFERI; LYME-DISEASE SPIROCHETE; TREPONEMA-DENTICOLA; SEQUENCE-ANALYSIS; PLASMID; AGENT; LEPTOSPIRA; CLONING; DNA; IDENTIFICATION AB The spirochetes include some important pathogenic bacteria, Treponema, Borrelia and Leptospira. The pathogeneses of these spirochetes are very diverse. In an attempt to learn more about the virulence factors among the spirochetes, their genetic organization and capacity have been studied. Structural analysis of the genome in Borrelia has shown that the genome is composed of one linear maxichromosome with additional linear minichromosomes as well as several supercoiled circular plasmids. Moreover, the molecular analysis of the terminal ends of one of the linear minichromosomes has revealed that this unique replicon has sequence similarities with poxviruses and particularly the viral agent of African swine fever. The presence of nucleic-acid-containing vesicles and its possible role in mediating DNA transfer between borreliae is an additional, very interesting feature of these organisms. Treponema does not contain any linear DNA, chromosomal or extrachromosomal, however molecular characterization of a 2.6-kb plasmid of Treponema denticola has been performed with the aim of establishing cloning vehicles to study the virulence properties of the genus Treponema. C1 INST PASTEUR,UNITE BACTERIOL MOLEC & MED,F-75724 PARIS 15,FRANCE. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NIAID,VECTORS & PATHOGENS LAB,ROCKY MT LABS,HAMILTON,MT 59840. RP BERGSTROM, S (reprint author), UMEA UNIV,DEPT MICROBIOL,S-90187 UMEA,SWEDEN. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 NR 50 TC 21 Z9 21 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD JUL-AUG PY 1992 VL 143 IS 6 BP 623 EP 628 DI 10.1016/0923-2508(92)90120-D PG 6 WC Microbiology SC Microbiology GA JM117 UT WOS:A1992JM11700010 PM 1475522 ER PT J AU RAGLAND, JD GOLDBERG, TE WEXLER, BE GOLD, JM TORREY, EF WEINBERGER, DR AF RAGLAND, JD GOLDBERG, TE WEXLER, BE GOLD, JM TORREY, EF WEINBERGER, DR TI DICHOTIC-LISTENING IN MONOZYGOTIC TWINS DISCORDANT AND CONCORDANT FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MONOZYGOTIC TWINS; DICHOTIC LISTENING; (SCHIZOPHRENIA) ID ACUTE PSYCHOTIC ILLNESS; HEMISPHERE DYSFUNCTION; PERCEPTUAL ASYMMETRY; CEREBRAL LATERALITY; CHILDREN; RISK AB Emotional and neutral word versions of the fused rhymed words dichotic listening test were administered to members of 18 pairs of monozygotic twins discordant for schizophrenia, 7 pairs concordant for schizophrenia, and 7 pairs of normal twins. In the discordant group, affected twins had smaller right ear advantages than did their unaffected cotwins for neutral words. The difference was completely attenuated with the presentation of emotional words or in less powerful between-group comparisons that included twins concordant for schizophrenia and normal twins. It is unlikely that this finding reflects an abnormality in the lateralized representation of language, both because we did not find a correlation between handedness scores and dichotic listening scores and because emotional stimuli normalized results. The finding may reflect abnormalities in the allocation of attention for priming language centers in the left hemisphere. 'At risk' subjects, i.e., the unaffected members of the discordant pairs, did not differ significantly from normal monozygotic twins on measures of dichotic listening. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. YALE UNIV,DEPT PSYCHIAT,NEW HAVEN,CT 06508. YALE UNIV,CONNECTICUT MENTAL HLTH CTR,NEW HAVEN,CT 06508. NR 45 TC 23 Z9 23 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 1992 VL 7 IS 2 BP 177 EP 183 DI 10.1016/0920-9964(92)90048-A PG 7 WC Psychiatry SC Psychiatry GA JJ736 UT WOS:A1992JJ73600011 PM 1515379 ER PT J AU PASS, HI POGREBNIAK, H AF PASS, HI POGREBNIAK, H TI PHOTODYNAMIC THERAPY FOR THORACIC MALIGNANCIES SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE EARLY STAGE LUNG CANCER; DYE LASER; PHOTOFRIN II; INTRAPLEURAL THERAPY AB Photodynamic therapy (PDT) is an experimental form of cancer therapy which employs photoactivation of a sensitizing chemical by light of a given wavelength via the production of toxic oxygen species. PDT causes local destruction of cancer, and relies on a therapeutic index between normal and malignant tissue since the latter seems to selectively retain the sensitizer. PDT has both direct tumoricidal effects as well as indirect effects on tumor vasculature causing an early hemorrhagic necrosis of tissue. The treatment has been used for the treatment of endobronchial obstruction by primary and metastatic tumors. Most recently, trials are being performed to evaluate this therapy as a surgical adjunct in the treatment of pleural malignancies such as mesothelioma. RP PASS, HI (reprint author), NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD JUL-AUG PY 1992 VL 8 IS 4 BP 217 EP 225 DI 10.1002/ssu.2980080407 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA JC721 UT WOS:A1992JC72100006 PM 1386470 ER PT J AU NUGENT, RP HILLIER, SL AF NUGENT, RP HILLIER, SL TI MUCOPURULENT CERVICITIS AS A PREDICTOR OF CHLAMYDIAL INFECTION AND ADVERSE PREGNANCY OUTCOME SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID TRACHOMATIS INFECTION; FEMALE ADOLESCENTS; PREVALENCE; DIAGNOSIS; WOMEN; MANIFESTATIONS; RISK AB The role of mucopurulent cervicitis in identifying pregnant women with Chlamydia trachomatis infection and poor pregnancy outcome was examined at the Johns Hopkins Hospital Obstetric Clinic in Baltimore, Maryland. The women studied were at high risk for chlamydial infection (14%), low birthweight (12%), and preterm delivery (13%). Yellow endocervical discharge on a cotton swab had a sensitivity of 23.9%, specificity of 89.4%, and positive predictive value of 28.6% for predicting chlamydial infection. The presence of greater-than-or-equal-to 30 polymorphonuclear cells per 1000 X field had a sensitivity of 25.0%, specificity of 87.6% and positive predictive value of 24.3%. Women with cervicitis defined by greater-than-or-equal-to 30 polymorphonuclear cells per 1000 X field were twice as likely to deliver a low-birthweight infant. Adjustment for potential confounding variables did not explain this association. The poor sensitivity, specificity, and positive predictive value of mucopurulent cervicitis suggests that this parameter is not a useful screening tool for chlamydial infection in pregnant women. However, mucopurulent cervicitis may be an indicator of increased risk for poor pregnancy outcome. C1 UNIV WASHINGTON,DEPT OBSTET & GYNECOL,SEATTLE,WA 98195. RP NUGENT, RP (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CRMC,PAMA,EXECUT PLAZA S,ROOM 450,ROCKVILLE,MD 20892, USA. FU NICHD NIH HHS [HD-3-2813] NR 16 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL-AUG PY 1992 VL 19 IS 4 BP 198 EP 202 DI 10.1097/00007435-199207000-00003 PG 5 WC Infectious Diseases SC Infectious Diseases GA JE766 UT WOS:A1992JE76600003 PM 1411834 ER PT J AU SCHIEWE, MC HANSEN, CT SCHMIDT, PM AF SCHIEWE, MC HANSEN, CT SCHMIDT, PM TI LACK OF ANTIBODY SPECIFICITY BY MOUSE TROPHECTODERM DURING IMMUNOSURGERY SO THERIOGENOLOGY LA English DT Article DE ANTIBODY; BLASTOCYST; IMMUNOSURGERY; INNER CELL MASS; TROPHECTODERM ID INNER CELL MASS; CHIMERAS; BLASTOCYST; TROPHOBLAST; EMBRYOS; TRANSPLANTATION; TISSUES; INVITRO; SHEEP; FATE AB Immunosurgery of blastocyst-stage embryos is an effective procedure for isolating the inner cell mass. The ability of rabbit sera antibodies produced to interspecific types of cells to bind to mouse trophectoderm antigens and mediate complement-reactive lysis was investigated. Fifty hatched and 25 expanded blastocysts per treatment were exposed to 1 of 7 heat-inactivated polyclonal antibodies (1:10 DMEM dilution) produced in rabbits to mouse brain cells (MBr), mouse lymphocytes (MLy), rat lymphocytes (RLy), hamster lymphocytes (HLy), cattle splenocytes (CSp), sheep splenocytes (SSp), and pig splenocytes (PSp). After subsequent incubation in a guinea pig complement solution (1:16 dilution) the embryos were assessed for trophectoderm lysis, and the inner cell masses were pipetted free of cellular debris. Fewer (P<0.01) hatched blastocysts were lysed completely when treated with RLy (60%), CSp (50%) and PSp (14%) antibodies compared the other treatment groups (100%). A similar response was observed with expanded blastocysts, with the exception that even fewer (P<0.01; RLy, 24%; CSp, 40%; PSp, 0%) were lysed completely. Forty percent of the PSp expanded blastocysts experienced no lysis, which was different (P<0.01) than in all the other treatments. Secondary experiments were performed to explain the cause of partial lytic response. Overall, the results indicate that interspecific antibodies can bind to murine trophectoderm surface antigens and mediate immunosurgical inner cell mass isolation, although the trophectoderm lytic response varied with antibody source. RP SCHIEWE, MC (reprint author), NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892, USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD JUL PY 1992 VL 38 IS 1 BP 21 EP 32 DI 10.1016/0093-691X(92)90215-D PG 12 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA JD227 UT WOS:A1992JD22700003 PM 16727115 ER PT J AU HEINDEL, JJ POWELL, CJ AF HEINDEL, JJ POWELL, CJ TI PHTHALATE ESTER EFFECTS ON RAT SERTOLI-CELL FUNCTION-INVITRO - EFFECTS OF PHTHALATE SIDE-CHAIN AND AGE OF ANIMAL SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INDUCED TESTICULAR ATROPHY; N-PENTYL PHTHALATE; DI-(2-ETHYLHEXYL) PHTHALATE; ACID ESTERS; DI(2-ETHYLHEXYL) PHTHALATE; PRIMARY CULTURES; TOXICITY; ZINC; TESTIS; MONO-(2-ETHYLHEXYL)PHTHALATE RP HEINDEL, JJ (reprint author), NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 73 Z9 75 U1 1 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL PY 1992 VL 115 IS 1 BP 116 EP 123 DI 10.1016/0041-008X(92)90374-2 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JC474 UT WOS:A1992JC47400015 PM 1321518 ER PT J AU ALBRIGHT, JF GOLDSTEIN, RA AF ALBRIGHT, JF GOLDSTEIN, RA TI IS THERE EVIDENCE OF AN IMMUNOLOGICAL BASIS FOR MULTIPLE CHEMICAL-SENSITIVITY SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT WORKSHOP ON MULTIPLE CHEMICAL SENSITIVITY CY SEP 20-21, 1991 CL WASHINGTON, DC SP ASSOC OCCUPAT & ENVIRONM CLIN ID FORMALDEHYDE; EXPOSURE; FOOD RP ALBRIGHT, JF (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,SOLAR BLDG,ROOM 4A22,BETHESDA,MD 20892, USA. NR 18 TC 10 Z9 10 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-AUG PY 1992 VL 8 IS 4 BP 215 EP 219 PG 5 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA JJ338 UT WOS:A1992JJ33800021 PM 1412488 ER PT J AU GAWLEY, RE REIN, KS KINOSHITA, M BADEN, DG AF GAWLEY, RE REIN, KS KINOSHITA, M BADEN, DG TI BINDING OF BREVETOXINS AND CIGUATOXIN TO THE VOLTAGE-SENSITIVE SODIUM-CHANNEL AND CONFORMATIONAL-ANALYSIS OF BREVETOXIN-B SO TOXICON LA English DT Note ID RED TIDE ORGANISM; PTYCHODISCUS-BREVIS; BRAIN SYNAPTOSOMES; GYMNODINIUM-BREVE; UNIQUE ACTIVATORS; TOXIN; RAT; ETHERS AB The marine toxins known generically as brevetoxins, as well as their structural relative ciguatoxin, are known as polyether ladder toxins, and bind uniquely to site 5 of the voltage-sensitive sodium channel. Rat brain synaptosome binding data show similarities in binding affinity for brevetoxins having the same structural (ladder) backbone, but different affinities between brevetoxins having different backbones. Ciguatoxin has a different backbone from the brevetoxins, but binds even more strongly to the same site. Could the flexibility of the backbone be related to their relative toxicities? As part of an effort to identify the common pharmacophore for the toxins, Monte Carlo methods were used to generate conformational models of the polyether ladder toxin brevetoxin B (PbTx-2) which shows significant flexibility at the juncture of the two 7-membered rings. C1 UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CORAL GABLES,FL 33124. RP GAWLEY, RE (reprint author), UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,DEPT CHEM,POB 249118,CORAL GABLES,FL 33124, USA. NR 30 TC 54 Z9 56 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD JUL PY 1992 VL 30 IS 7 BP 780 EP 785 DI 10.1016/0041-0101(92)90014-V PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JD020 UT WOS:A1992JD02000014 PM 1324537 ER PT J AU DEKABAN, G INWOOD, M WATERS, D DROUIN, J TEITEL, J AF DEKABAN, G INWOOD, M WATERS, D DROUIN, J TEITEL, J TI ABSENCE OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II INFECTION IN AN ONTARIO HEMOPHILIA POPULATION SO TRANSFUSION LA English DT Article ID MULTIPLE-SCLEROSIS; GENE; RETROVIRUSES; DISEASE AB Two hundred ninety-three serum samples from Ontario hemophiliacs and 200 samples from human immunodeficiency virus-positive blood donors were screened for the presence of antibodies to human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunosorbent assay, radioimmunoassay, and Western blot techniques. None of the serum samples provided unequivocal positive results, but several samples gave inconclusive results. Of the hemophiliacs with inconclusive serologic results from whom peripheral blood lymphocyte DNA could be obtained, all were negative for HTLV-I and HTLV type II (HTLV-II) sequences as determined by polymerase chain reaction (PCR). PCR was also performed on a lymph node biopsy sample taken from a hemophiliac who developed a rare T-cell lymphoma; the sample was negative for HTLV-I and -II sequences. These results indicate that Ontario hemophiliacs have not been exposed to HTLV-I or HTLV-II. C1 UNIV WESTERN ONTARIO, ST JOSEPHS HLTH CTR, S WESTERN ONTARIO REG HEMOPHILIA PROGRAM, LONDON N6A 3K7, ONTARIO, CANADA. ST MICHAELS HOSP, ADULT REG HEMOPHILIA PROGRAM, TORONTO M5B 1W8, ONTARIO, CANADA. UNIV OTTAWA, OTTAWA GEN HOSP, ADULT REG HEMOPHILIA PROGRAM, OTTAWA K1N 6N5, ONTARIO, CANADA. NCI, FREDERICK CANC RES & DEV CTR, AIDS VACCINE PROGRAM, FREDERICK, MD 21701 USA. RP DEKABAN, G (reprint author), UNIV WESTERN ONTARIO, JOHN ROBERTS RES INST, IMMUNOL GRP, LONDON N6A 3K7, ONTARIO, CANADA. FU NCI NIH HHS [N01-CO-74102] NR 9 TC 3 Z9 3 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 JUL-AUG PY 1992 VL 32 IS 6 BP 513 EP 516 DI 10.1046/j.1537-2995.1992.32692367193.x PG 4 WC Hematology SC Hematology GA JJ564 UT WOS:A1992JJ56400005 PM 1502703 ER PT J AU DAVEY, RJ MCCOY, NC YU, M SULLIVAN, JA SPIEGEL, DM LEITMAN, SF AF DAVEY, RJ MCCOY, NC YU, M SULLIVAN, JA SPIEGEL, DM LEITMAN, SF TI THE EFFECT OF PRESTORAGE IRRADIATION ON POSTTRANSFUSION RED-CELL SURVIVAL SO TRANSFUSION LA English DT Article ID VERSUS-HOST DISEASE; POTASSIUM LEVELS; BLOOD PRODUCTS; TRANSFUSION; GRAFT; GUIDELINES; STORAGE AB Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4-degrees-C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4-degrees-C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/-206 vs. 429 +/- 194 g/d L [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p < 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p < 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3-mu-M/g Hb, p < 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p < 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy. RP DAVEY, RJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,LAB SERV SECT,BETHESDA,MD 20892, USA. NR 23 TC 73 Z9 74 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL-AUG PY 1992 VL 32 IS 6 BP 525 EP 528 DI 10.1046/j.1537-2995.1992.32692367195.x PG 4 WC Hematology SC Hematology GA JJ564 UT WOS:A1992JJ56400007 PM 1502705 ER PT J AU HAYES, JJ WOLFFE, AP AF HAYES, JJ WOLFFE, AP TI EXPERIMENTAL-DETERMINATION OF DNA HELICAL REPEATS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter ID NUCLEOSOME CORE DNA; PERIODICITY; CHROMATIN; SEQUENCE RP HAYES, JJ (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1992 VL 17 IS 7 BP 250 EP 250 DI 10.1016/0968-0004(92)90403-V PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE102 UT WOS:A1992JE10200004 PM 1502726 ER PT J AU UHL, GR AF UHL, GR TI NEUROTRANSMITTER TRANSPORTERS (PLUS) - A PROMISING NEW GENE FAMILY SO TRENDS IN NEUROSCIENCES LA English DT Review ID GAMMA-AMINOBUTYRIC ACID; XENOPUS-LAEVIS OOCYTES; RAT-BRAIN; EXPRESSION; NA+/GLUCOSE; COCAINE; NEUROTOXIN; CLONING; CHOLINE; NEURONS AB Neurotransmitter transporter genes encode proteins with 12 putative transmembrane regions, which mediate Na+-dependent reaccumulation of released neurotransmitters into presynaptic terminals and are the sites of action of important abused and therapeutic drugs. Studies of these genes show promise for improving our understanding of transport mechanisms and modes of drug action, and may even uncover previously unanticipated neurotransmitters. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP UHL, GR (reprint author), NIDA,CTR ADDICT RES,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21224, USA. NR 45 TC 167 Z9 169 U1 3 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 1992 VL 15 IS 7 BP 265 EP 268 DI 10.1016/0166-2236(92)90068-J PG 4 WC Neurosciences SC Neurosciences & Neurology GA HZ488 UT WOS:A1992HZ48800013 PM 1381123 ER PT J AU MORGANTIKOSSMANN, MC KOSSMANN, T WAHL, SM AF MORGANTIKOSSMANN, MC KOSSMANN, T WAHL, SM TI CYTOKINES AND NEUROPATHOLOGY SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID TUMOR-NECROSIS-FACTOR; CENTRAL NERVOUS-SYSTEM; IMMUNODEFICIENCY-VIRUS EXPRESSION; GROWTH-FACTOR; FACTOR-ALPHA; BRAIN-TISSUE; CELLS; INTERLEUKIN-1; ASTROCYTES; HIV-1 AB Inflammatory processes in the brain require the cooperation of immunocompetent cells and glial cells, which communicate by secreting bidirectional mediators. Resident cells within the nervous system can synthesize and secrete inflammatory cytokines, as well as neuropeptides, contributing to the response within the CNS to injury or immunological challenge. Although the mechanisms of cell activation and immune interaction are poorly understood, accumulating evidence implicates these pathways in neuropathogenesis, as described here by Sharon Wahl and colleagues. For example, in the acquired immune deficiency syndrome (AIDS), HIV-1-induced nervous system dysfunction and dementia are associated with the presence of infiltrating leukocytes and the release of inflammatory cytokines. Defining the pathways of cytokine dysregulation and neurotoxicity invoked by the infiltrating leukocytes, as well as the contribution of the neural cells themselves, may help to identify mechanisms of intervention in this and other debilitating CNS diseases. C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. RP MORGANTIKOSSMANN, MC (reprint author), UNIV HOSP ZURICH,DEPT SURG,DIV TRAUMA SURG,CH-8091 ZURICH,SWITZERLAND. NR 49 TC 143 Z9 143 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 JUL PY 1992 VL 13 IS 7 BP 286 EP 291 DI 10.1016/0165-6147(92)90087-M PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JC389 UT WOS:A1992JC38900008 PM 1509523 ER PT J AU TAKAHASHI, K MAITA, K KUWAHARA, M HARADA, T MARONPOT, RR AF TAKAHASHI, K MAITA, K KUWAHARA, M HARADA, T MARONPOT, RR TI EOSINOPHILIC GLOBULE CELLS IN MOUSE MFH-LIKE SARCOMAS - LECTIN HISTOCHEMISTRY SO VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY LA English DT Article DE MOUSE; EOSINOPHILIC GLOBULE CELL; MALIGNANT FIBROUS HISTIOCYTOMA; GRANULAR METRIAL GLAND CELL; LECTIN HISTOCHEMISTRY ID METRIAL GLAND-CELLS; EUROPAEUS-I LECTIN; BINDING-SITES; DIFFERENTIATION; HISTIOCYTES; LESIONS; MARKER; TUMORS; UTERUS AB Lectin binding patterns in ten mouse malignant fibrous histiocytoma (MFH)-like sarcomas containing eosinophilic globule (EG) cells and in granular metrial gland (GMG) cells of mouse placenta were stained with nine lectins (Con A, LCA, WGA, DBA, SBA, e-PHA, PNA, RCA-1 and UEA-1) by an avidin-biotin-peroxidase-complex method. EG cells stained strongly with DBA, SBA and PNA which are specific for N-acetyl-D-galactosamine and/or D-galactose. DBA and SBA bound throughout the cytoplasm including the globules; PNA reacted preferentially at the cell surface. There was no evidence that these three lectins were reactive for immature EG cells. WGA, RCA-1 and e-PHA also gave a slightly to moderately positive reaction to globules of EG cells. The results indicate that the globules contain abundant O-linked sequences of sugars, but also a few N-linked residues. MFH tumor cells showed a variable degree of binding with Con A, RCA-I, and WGA, but did not react with DBA, SBA and PNA. On the other hand, GMG cells exhibited specific affinities for DBA, SBA and PNA with staining patterns similar to those of EG cells. These findings suggest that EG and GMG cells may be of the same cellular lineage. C1 INST ENVIRONM TOXICOL,DIV TOXICOL,SUZUKI CHO 2,772 KODAIRA SHI,TOKYO 187,JAPAN. NIEHS,RES TRIANGLE PK,NC 27709. NR 22 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6075 J9 VIRCHOWS ARCH B JI Virchows Arch. B-Cell Molec. Pathol. PD JUL PY 1992 VL 62 IS 2 BP 89 EP 95 DI 10.1007/BF02899669 PG 7 WC Pathology SC Pathology GA JF152 UT WOS:A1992JF15200003 PM 1355325 ER PT J AU STOHLMAN, SA KYUWA, S COHEN, M BERGMANN, C POLO, JM YEH, J ANTHONY, R KECK, JG AF STOHLMAN, SA KYUWA, S COHEN, M BERGMANN, C POLO, JM YEH, J ANTHONY, R KECK, JG TI MOUSE HEPATITIS-VIRUS NUCLEOCAPSID PROTEIN-SPECIFIC CYTOTOXIC LYMPHOCYTES-T ARE L(D) RESTRICTED AND SPECIFIC FOR THE CARBOXY TERMINUS SO VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; JHM MHV-4 VIRUS; MONOCLONAL-ANTIBODIES; MURINE CORONAVIRUSES; CELL CLONES; ANTIGENIC RELATIONSHIPS; STRAIN JHM; EXPRESSION; INFECTION; PROTECTION C1 UNIV SO CALIF,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90033. UNIV TOKYO,DEPT ANIM PATHOL,TOKYO 113,JAPAN. NIH,VIRAL DIS LAB,BETHESDA,MD 20892. RP STOHLMAN, SA (reprint author), UNIV SO CALIF,SCH MED,DEPT MICROBIOL,LOS ANGELES,CA 90033, USA. FU NINDS NIH HHS [NS18146] NR 34 TC 45 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1992 VL 189 IS 1 BP 217 EP 224 PG 8 WC Virology SC Virology GA HY278 UT WOS:A1992HY27800023 PM 1376538 ER PT J AU GAZIT, A SARID, R MASHIAH, P ARCHAMBAULT, D DAHLBERG, JE TRONICK, SR YANIV, A AF GAZIT, A SARID, R MASHIAH, P ARCHAMBAULT, D DAHLBERG, JE TRONICK, SR YANIV, A TI DEFECTIVE VIRAL PARTICLES IN CAPRINE ARTHRITIS ENCEPHALITIS-VIRUS INFECTION SO VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; MOLECULAR-CLONING; IMMUNODEFICIENCY DISEASE; ANEMIA VIRUS; NUCLEOTIDE-SEQUENCE; DNA; RETROVIRUS; INTEGRATION; PROVIRUSES C1 TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN MICROBIOL, TEL AVIV, ISRAEL. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 36 TC 3 Z9 3 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 0042-6822 J9 VIROLOGY JI Virology PD JUL PY 1992 VL 189 IS 1 BP 344 EP 349 DI 10.1016/0042-6822(92)90713-Y PG 6 WC Virology SC Virology GA HY278 UT WOS:A1992HY27800039 PM 1318611 ER PT J AU JENSEN, RT ZHOU, ZC GU, ZF KITSUKAWA, Y HONDA, T MATON, PN AF JENSEN, RT ZHOU, ZC GU, ZF KITSUKAWA, Y HONDA, T MATON, PN TI INTERACTION OF CALCITONIN GENE RELATED PEPTIDES WITH PANCREATIC ACINAR-CELLS AND DISPERSED GASTRIC SMOOTH-MUSCLE CELLS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID VASOACTIVE INTESTINAL PEPTIDE; COOH-TERMINAL FRAGMENTS; GUINEA-PIG; SENSORY NEURONS; ACID SECRETION; BINDING-SITES; SUBSTANCE-P; RECEPTOR; CGRP; RAT RP JENSEN, RT (reprint author), NIH,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892, USA. NR 61 TC 11 Z9 11 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 30 PY 1992 VL 657 BP 268 EP 288 DI 10.1111/j.1749-6632.1992.tb22775.x PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JL499 UT WOS:A1992JL49900023 PM 1379015 ER PT J AU SKOFITSCH, G JACOBOWITZ, DM AF SKOFITSCH, G JACOBOWITZ, DM TI CALCITONIN AND CALCITONIN GENE RELATED PEPTIDE RECEPTOR-BINDING SITES IN THE RAT CENTRAL-NERVOUS-SYSTEM SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NIMH,CLIN SCI LAB,HISTOPHARMACOL SECT,BETHESDA,MD 20892. RP SKOFITSCH, G (reprint author), GRAZ UNIV,DEPT ZOOL,A-8010 GRAZ,AUSTRIA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 30 PY 1992 VL 657 BP 420 EP 422 DI 10.1111/j.1749-6632.1992.tb22788.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JL499 UT WOS:A1992JL49900036 PM 1322092 ER PT J AU KRESSE, A JACOBOWITZ, DM SKOFITSCH, G AF KRESSE, A JACOBOWITZ, DM SKOFITSCH, G TI DISTRIBUTION OF CALCITONIN GENE RELATED PEPTIDE IN THE CENTRAL-NERVOUS-SYSTEM OF THE RAT BY IMMUNOCYTOCHEMISTRY AND INSITU HYBRIDIZATION HISTOCHEMISTRY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 GRAZ UNIV,DEPT ZOOL,A-8010 GRAZ,AUSTRIA. NIMH,CLIN SCI LAB,HISTOPHARMACOL SECT,BETHESDA,MD 20892. NR 3 TC 12 Z9 14 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 30 PY 1992 VL 657 BP 455 EP 457 DI 10.1111/j.1749-6632.1992.tb22798.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JL499 UT WOS:A1992JL49900046 PM 1637098 ER PT J AU MIYASAKA, H LI, SSL AF MIYASAKA, H LI, SSL TI THE CDNA CLONING, NUCLEOTIDE-SEQUENCE AND EXPRESSION OF AN INTRACELLULAR PROTEIN TYROSINE PHOSPHATASE FROM MOUSE TESTIS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MALE GERM LINE; TRANSCRIPT; FAMILY; KINASES; ENCODES; CELLS C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 25 TC 20 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 30 PY 1992 VL 185 IS 3 BP 818 EP 825 DI 10.1016/0006-291X(92)91700-Z PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JB541 UT WOS:A1992JB54100004 PM 1378268 ER PT J AU CECCHINI, S IOSSA, A BONARDI, R GUSTAVINO, C CIATTO, S AF CECCHINI, S IOSSA, A BONARDI, R GUSTAVINO, C CIATTO, S TI EVALUATION OF THE SENSITIVITY OF CERVICOGRAPHY IN A CONSECUTIVE COLPOSCOPIC SERIES SO TUMORI LA English DT Article ID INVASIVE CERVICAL-CANCER; PAPANICOLAOU SMEAR; SCREENING-PROGRAM; CYTOLOGY; RATES; FLORENCE AB Cervicography was performed in 606 women referred for colposcopy. Cervigrams were blindly reviewed by two independent readers. The positivity rate at cervicography was high (operator A = 50 %, B = 58.8 %). The sensitivity for papillomavirus infection (HPV)/cervical intraepithelial neoplasia I (CIN I) (n = 141) was 79.4 % for operator A and 80.8 % for operator B. The sensitivity for CIN II or more severe lesions (n = 22) was 95.2 % and 90.5 % for operators A and B, respectively. The positive predictive value for HPV/CIN I or CIN II, or more severe lesions was 36.9 % and 6.9 % for operator A and 32.1 % and 5.3 % for operator B, respectively. Interobserver variability was acceptable (kappa = 0.62). Cervicography suspected 27 HPV/CIN I, 1 CIN II and 1 CIN III which showed no cytologic abnormalities. This study confirms that cervicography has a good sensitivity for cervical lesions, but it is based on a selected series, not representative of a screening condition. The combination of cervicography and cytology in screening is presently under evaluation in a prospecitve study of screened women. C1 NATL CANC INST,GENOA,ITALY. RP CECCHINI, S (reprint author), CTR STUDIO PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. NR 18 TC 9 Z9 9 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD JUN 30 PY 1992 VL 78 IS 3 BP 211 EP 213 PG 3 WC Oncology SC Oncology GA JQ023 UT WOS:A1992JQ02300013 PM 1332234 ER PT J AU HERKENHAM, M AF HERKENHAM, M TI CANNABINOID RECEPTOR LOCALIZATION IN BRAIN - RELATIONSHIP TO MOTOR AND REWARD SYSTEMS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FREELY-MOVING RATS; ANALGESIC PROPERTIES; MULTIPLE-SCLEROSIS; RHESUS-MONKEYS; BASAL GANGLIA; DELTA-9-TETRAHYDROCANNABINOL; TETRAHYDROCANNABINOLS; PHARMACOLOGY; SITES; SPASTICITY RP HERKENHAM, M (reprint author), NIMH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D-15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 59 TC 71 Z9 73 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1992 VL 654 BP 19 EP 32 DI 10.1111/j.1749-6632.1992.tb25953.x PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM220 UT WOS:A1992JM22000004 PM 1385932 ER PT J AU HOFFMAN, PL GRANT, KA SNELL, LD REINLIB, L IORIO, K TABAKOFF, B AF HOFFMAN, PL GRANT, KA SNELL, LD REINLIB, L IORIO, K TABAKOFF, B TI NMDA RECEPTORS - ROLE IN ETHANOL WITHDRAWAL SEIZURES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID GAMMA-AMINOBUTYRIC ACID; OPERATED CHLORIDE CHANNELS; SPINAL-CORD NEURONS; AUDIOGENIC-SEIZURES; RAT-BRAIN; GABA; ALCOHOL; COMPLEX; MICE; INHIBITION C1 NIAAA, PHYSIOL & PHARMACOL STUDIES, ROCKVILLE, MD 20852 USA. RP HOFFMAN, PL (reprint author), UNIV COLORADO, HLTH SCI CTR, DEPT PHARMACOL, C236, 4200 E 9TH AVE, DENVER, CO 80262 USA. NR 55 TC 48 Z9 48 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1992 VL 654 BP 52 EP 60 DI 10.1111/j.1749-6632.1992.tb25955.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM220 UT WOS:A1992JM22000006 PM 1321581 ER PT J AU BOJA, JW CLINE, EJ CARROLL, FI LEWIN, AH PHILIP, A DANNALS, R WONG, D SCHEFFEL, U KUHAR, MJ AF BOJA, JW CLINE, EJ CARROLL, FI LEWIN, AH PHILIP, A DANNALS, R WONG, D SCHEFFEL, U KUHAR, MJ TI HIGH POTENCY COCAINE ANALOGS - NEUROCHEMICAL, IMAGING, AND BEHAVIORAL-STUDIES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CENTRAL NERVOUS-SYSTEM; LIGAND-BINDING; DOPAMINE TRANSPORTERS; NONHUMAN-PRIMATES; CAUDATE-PUTAMEN; H-3 WIN-35,428; RAT STRIATUM; SITES; RECEPTORS; BRAIN C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. JOHNS HOPKINS MED INST,DIV NUCL MED & RADIAT HLTH SCI,BALTIMORE,MD 21205. RP BOJA, JW (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 28 Z9 28 U1 2 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1992 VL 654 BP 282 EP 291 DI 10.1111/j.1749-6632.1992.tb25974.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM220 UT WOS:A1992JM22000025 PM 1632587 ER PT J AU POST, RM WEISS, SRB FONTANA, D PERT, A AF POST, RM WEISS, SRB FONTANA, D PERT, A TI CONDITIONED SENSITIZATION TO THE PSYCHOMOTOR STIMULANT COCAINE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PIMOZIDE BLOCKS ESTABLISHMENT; C-FOS; AMPHETAMINE-PSYCHOSIS; REWARD ASSOCIATIONS; NUCLEUS-ACCUMBENS; VENTRAL STRIATUM; ANIMAL-MODEL; TOLERANCE; AMYGDALA; DOPAMINE RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 63 TC 69 Z9 70 U1 2 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1992 VL 654 BP 386 EP 399 DI 10.1111/j.1749-6632.1992.tb25983.x PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM220 UT WOS:A1992JM22000034 PM 1632592 ER PT J AU COLOMBO, G GRANT, KA AF COLOMBO, G GRANT, KA TI NMDA RECEPTOR COMPLEX ANTAGONISTS HAVE ETHANOL-LIKE DISCRIMINATIVE STIMULUS EFFECTS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID ASPARTATE RP COLOMBO, G (reprint author), NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,RECEPTOR MECHANISMS SECT,ROCKVILLE,MD 20852, USA. NR 5 TC 23 Z9 23 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 28 PY 1992 VL 654 BP 421 EP 423 DI 10.1111/j.1749-6632.1992.tb25986.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM220 UT WOS:A1992JM22000037 PM 1385933 ER PT J AU BIGGAR, RJ DUNSMORE, N KURMAN, RJ SHAH, KV KORDOR, J COTTONI, F HATZAKIS, A GIGASE, PL AF BIGGAR, RJ DUNSMORE, N KURMAN, RJ SHAH, KV KORDOR, J COTTONI, F HATZAKIS, A GIGASE, PL TI FAILURE TO DETECT HUMAN PAPILLOMAVIRUS IN KAPOSIS-SARCOMA SO LANCET LA English DT Letter C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. RETPATOL INST,ODENSE,DENMARK. CLIN DERMATOL,SASSARI,ITALY. UNIV ATHENS,SCH MED,ATHENS,GREECE. INST TROP MED PRINCE LEOPOLD,B-2000 ANTWERP,BELGIUM. RP BIGGAR, RJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 7 TC 19 Z9 19 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 27 PY 1992 VL 339 IS 8809 BP 1604 EP 1605 DI 10.1016/0140-6736(92)91866-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JB202 UT WOS:A1992JB20200027 PM 1351572 ER PT J AU DELCERRO, M NOTTER, MF SEIGEL, G LAZAR, E CHADER, G DELCERRO, C AF DELCERRO, M NOTTER, MF SEIGEL, G LAZAR, E CHADER, G DELCERRO, C TI INTRARETINAL XENOGRAFTS OF DIFFERENTIATED HUMAN RETINOBLASTOMA CELLS INTEGRATE WITH THE HOST RETINA SO BRAIN RESEARCH LA English DT Article DE RETINOBLASTOMA; Y79-CELL; TRANSPLANT; MITOTIC ARREST; XENOGRAFT; DIFFERENTIATION ID NEURO-BLASTOMA CELLS; GLIAL MARKERS; Y-79; EXPRESSION; BUTYRATE; BRAIN; LINES; GENE; RAT AB We report on the successful use of chemically modified Y79 human retinoblastoma cells for intraretinal xenografting into damaged adult mammalian eyes. Y79 cells were exposed in vitro to retinoic acid/butyrate to induce differentiation. Using a multisite transplantation method, the suspension was injected into the subretinal space of Fischer 344 rats. The survival, integration, and differentiation potential of these cells was studied, following their return to the intraocular milieu from which the progenitor cells originated. The grafted cells survived and differentiated into immature photoreceptor elements in the subretinal and intraretinal locations, as multiple clusters of rosette-forming cells intimately attached to the host neuroretina. The differentiation process included development of synaptic connectivity of the ribbon type with the surrounding neuropil. No signs of renewed cell division were found within grafts performed on 42 rat eyes, and there was no indication of cell-mediated host reaction against the transplants. This study indicates that tumorigenicity can be suppressed in mitotically arrested Y79 cells. and that these cells are capable of undergoing differentiation in vivo. This provides evidence of the remarkable differentiation properties of human retinoblastomas while indicating that Y79 cells may ultimately be able to substitute for fetal cells in experimental retinal transplantation. C1 NIH,BETHESDA,MD 20892. RP DELCERRO, M (reprint author), UNIV ROCHESTER,SCH MED,DEPT NEUROBIOL & ANAT,PO 603,ROCHESTER,NY 14642, USA. FU NIA NIH HHS [T32AG00107]; PHS HHS [NEI05262, NEI052314] NR 28 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 26 PY 1992 VL 583 IS 1-2 BP 12 EP 22 PG 11 WC Neurosciences SC Neurosciences & Neurology GA JD615 UT WOS:A1992JD61500002 PM 1504822 ER PT J AU BELENKY, M CASTEL, M YOUNG, WS GAINER, H COHEN, S AF BELENKY, M CASTEL, M YOUNG, WS GAINER, H COHEN, S TI ULTRASTRUCTURAL IMMUNOLOCALIZATION OF RAT OXYTOCIN-NEUROPHYSIN IN TRANSGENIC MICE EXPRESSING THE RAT OXYTOCIN GENE SO BRAIN RESEARCH LA English DT Note DE PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEUS; OXYTOCIN; NEUROPHYSIN; IMMUNOCYTOCHEMISTRY ID CORTICOTROPIN-RELEASING FACTOR; HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; NEUROSECRETORY NEURONS; MONOCLONAL-ANTIBODIES; VASOPRESSIN; LOCALIZATION; INNERVATION; NUCLEUS; MOUSE; GOLD AB Cell-specific expression of the rat oxytocin (OT)-neurophysin transgene in mice was achieved using a construct containing both OT and vasopressin genes (Young III, W.S., Reynolds, K., Shepard, E.A., Gainer, H. and Castel, M., Cell-specific expression of the rat oxytocin gene in transgenic mice, J. Neuroendocrinol., 2 (1990) 1-9). The present study describes the distribution of the protein products of these genes in various regions of the cell, and determines whether the transgenic rat and endogenous mouse OT-neurophysins are colocalized within the same neurosecretory granules. Two monoclonal antibodies against OT-neurophysins were used: PS38 which can react with both rat and mouse OT-neurophysin (pan-specific), and PS67 which is specific for rat OT-neurophysin only. Various approaches to double immunolabeling at the ultrastructural level were employed; these included: (1) pre-embedding immunoperoxidase followed by post-embedding immunogold; (2) Post-embedding immunolabeling using gold particles of different sizes; and (3) labeling of consecutive ultrathin sections with different antibodies. Results from each of these approaches showed that both in the transgenic mouse and in the rat (used as control), immunocytochemical labeling for both PS38 and PS67 occurred in the same OT-ergic neurosecretory granules. In the control mouse, only PS38 elicited labeling. Hence, it may be concluded that the protein and peptide products of the transgene and the endogenous gene for OT-neurophysin are being processed similarly in the cell and finally concentrated together in the same neurosecretory granules. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NICH,NEUROCHEM LAB,BETHESDA,MD. RP BELENKY, M (reprint author), HEBREW UNIV JERUSALEM,SILBERMAN INST LIFE SCI,DEPT EXPTL ZOOL,IL-91904 JERUSALEM,ISRAEL. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 24 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 26 PY 1992 VL 583 IS 1-2 BP 279 EP 286 PG 8 WC Neurosciences SC Neurosciences & Neurology GA JD615 UT WOS:A1992JD61500031 PM 1504834 ER PT J AU ZATZ, M AF ZATZ, M TI AGENTS THAT AFFECT CALCIUM INFLUX CAN CHANGE CYCLIC-NUCLEOTIDE LEVELS IN CULTURED CHICK PINEAL CELLS SO BRAIN RESEARCH LA English DT Note DE MELATONIN; CIRCADIAN RHYTHM ID N-ACETYLTRANSFERASE ACTIVITY; PHOTOENDOCRINE TRANSDUCTION; MELATONIN PRODUCTION; GMP; LIGHT; OSCILLATION; RHYTHM; GLAND; CAMP; PACEMAKER AB Previous experiments examined interactions among the effects of cyclic AMP and calcium-related agents on melatonin output by cultured chick pineal cells, and suggested that changes in calcium influx might act through cyclic AMP. Here, effects of calcium-related agents and manipulations on cyclic AMP (and cyclic GMP) levels are demonstrated directly. These effects support a role for cyclic AMP (but not cyclic GMP) in the effects of changes in calcium influx on melatonin production by these cells. RP ZATZ, M (reprint author), NIMH,BIOCHEM PHARMACOL SECT,CELL BIOL LAB,BLDG 36,RM 2A-17,BETHESDA,MD 20892, USA. NR 27 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 26 PY 1992 VL 583 IS 1-2 BP 304 EP 307 PG 4 WC Neurosciences SC Neurosciences & Neurology GA JD615 UT WOS:A1992JD61500036 PM 1380398 ER PT J AU ROBEY, EA RAMSDELL, F KIOUSSIS, D SHA, W LOH, D AXEL, R FOWLKES, BJ AF ROBEY, EA RAMSDELL, F KIOUSSIS, D SHA, W LOH, D AXEL, R FOWLKES, BJ TI THE LEVEL OF CD8 EXPRESSION CAN DETERMINE THE OUTCOME OF THYMIC SELECTION SO CELL LA English DT Article ID T-CELL-RECEPTOR; TRANSGENIC MICE; NEGATIVE SELECTION; POSITIVE SELECTION; ANTIGEN RECEPTOR; LYMPHOCYTES-T; KINASE P56LCK; TOLERANCE; DELETION; SELF AB During thymic development, thymocytes that can recognize major histocompatability complex (MHC) molecules on thymic epithelial cells are selected to survive and mature (positive selection), whereas thymocytes that recognize MHC on hematopoietic cells are destroyed (negative selection). It is not known how MHC recognition can mediate both death and survival. One model to explain this paradox proposes that thymocytes whose T cell antigen receptors (TCRs) recognize MHC with high affinity are eliminated by negative selection, whereas low affinity TCR-MHC interactions are sufficient to mediate positive selection. Here we report that, while the expression of a 2C TCR transgene leads to positive selection of thymocytes in H-2b mice, expression of both a CD8 transgene and a 2C TCR transgene causes negative selection. This observation indicates that quantitative differences in TCR-MHC recognition are a critical determinant of T cell fate, a finding predicted by the affinity model for thymic selection. C1 WASHINGTON UNIV,DEPT IMMUNOL,ST LOUIS,MO 63110. WASHINGTON UNIV,HOWARD HUGHES MED INST,ST LOUIS,MO 63110. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NATL INST MED RES,GENE STRUCT & EXPRESS LAB,LONDON NW7 1AA,ENGLAND. COLUMBIA UNIV,DEPT BIOCHEM & MOLEC BIOPHYS,NEW YORK,NY 10032. COLUMBIA UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10032. NR 38 TC 143 Z9 144 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 26 PY 1992 VL 69 IS 7 BP 1089 EP 1096 DI 10.1016/0092-8674(92)90631-L PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JA431 UT WOS:A1992JA43100004 PM 1617724 ER PT J AU LETOURNEUR, F KLAUSNER, RD AF LETOURNEUR, F KLAUSNER, RD TI A NOVEL DI-LEUCINE MOTIF AND A TYROSINE-BASED MOTIF INDEPENDENTLY MEDIATE LYSOSOMAL TARGETING AND ENDOCYTOSIS OF CD3 CHAINS SO CELL LA English DT Article ID CELL ANTIGEN RECEPTOR; ENDOPLASMIC-RETICULUM; MEMBRANE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; TRANSMEMBRANE PROTEINS; INTERLEUKIN-2 RECEPTOR; MOLECULAR-CLONING; ACID-PHOSPHATASE; INTERNALIZATION; DEGRADATION AB Partial complexes of the T cell antigen receptor lacking zeta-chains are delivered to lysosomes. Chimeric proteins composed of the Tac antigen fused to the cytoplasmic domains of each CD3 chain has allowed the identification of lysosomal targeting sequences. Tac-gamma and Tac-delta chimeras are retained in the endoplasmic reticulum because of the presence of basic residues reminiscent of sequences responsible for the localization of endoplasmic reticulum resident proteins. Truncation of these retention motifs revealed lysosomal targeting of both Tac-gamma and delta-chimeras. A di-leucine- and a tyrosine-based motif are individually sufficient to induce both endocytosis and delivery to lysosomes of Tac. In contrast with chimeras containing only one of these motifs, the chimera containing both was predominantly delivered directly to lysosomes without going through the cell surface. These two sequences may represent two families of targeting motifs that determine the fate of proteins within the peripheral membrane system. RP LETOURNEUR, F (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 59 TC 486 Z9 489 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 26 PY 1992 VL 69 IS 7 BP 1143 EP 1157 DI 10.1016/0092-8674(92)90636-Q PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JA431 UT WOS:A1992JA43100009 PM 1535555 ER PT J AU TORRES, AR PETERSON, EA AF TORRES, AR PETERSON, EA TI PURIFICATION OF COMPLEX PROTEIN MIXTURES BY ION-EXCHANGE DISPLACEMENT CHROMATOGRAPHY USING SPACER DISPLACERS SO JOURNAL OF CHROMATOGRAPHY LA English DT Article; Proceedings Paper CT HONORARY SYMP ON THE OCCASION OF THE SEVENTIETH BIRTHDAY OF JERKER O PORATH : BIOCHEMICAL SEPARATION TECHNOLOGY CY JUN 16-19, 1991 CL UPPSALA, SWEDEN ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CARBOXYMETHYLDEXTRANS; ELECTROPHORESIS; SERUM AB The anion-exchange separation of complex protein mixtures by displacement chromatography using spacer displacers driven by high-affinity final displacers is demonstrated. Guinea pig serum was separated on a medium-resolution adsorbent using a single heterogenous mixture of carboxymethyldextran displacers to space the protein components. Mouse liver cytosol was separated on a low-resolution adsorbent using six carboxymethyldextran spacer displacers of increasing column affinity. The demonstration of the purification of alkaline phosphatase from E. coli periplasm by displacement chromatography on a high-performance liquid chromatography column is reviewed. The benefits of spacer displacers for separating minor components from complex biological protein mixtures is discussed. A simplified method for preparing carboxymethyldextran displacers is presented. C1 NCI,BIOCHEM LAB,BALTIMORE,MD 21201. RP TORRES, AR (reprint author), BIOFRACTIONAT,1725 S STATE HIGHWAY 89-91,LOGAN,UT 84321, USA. NR 23 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD JUN 26 PY 1992 VL 604 IS 1 BP 39 EP 46 DI 10.1016/0021-9673(92)85526-Y PG 8 WC Chemistry, Analytical SC Chemistry GA JC599 UT WOS:A1992JC59900007 PM 1379252 ER PT J AU HURYN, DM SLUBOSKI, BC TAM, SY WEIGELE, M SIM, I ANDERSON, BD MITSUYA, H BRODER, S AF HURYN, DM SLUBOSKI, BC TAM, SY WEIGELE, M SIM, I ANDERSON, BD MITSUYA, H BRODER, S TI SYNTHESIS AND ANTI-HIV ACTIVITY OF ISONUCLEOSIDES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; CARBOCYCLIC NUCLEOSIDES; AZIDOTHYMIDINE AZT; DOUBLE-BLIND; ANALOGS; 2',3'-DIDEOXYADENOSINE AB A series of isomeric 2',3'-dideoxynucleosides which contains a modified carbohydrate moiety has been prepared. This class of compounds was designed to mimic the activity of known anti-HIV dideoxynucleosides, while imparting enhanced chemical and enzymatic stability. Isonucleosides containing the standard heterocyclic bases (A, C, G, T) were synthesized via nucleophilic addition of the base to an isomeric sugar unit. Modified derivatives were generated by manipulation of the intact isonucleoside. Two of the compounds prepared, iso-ddA (1) and iso-ddG (6), exhibit significant and selective anti-HIV activity, as well as beneficial hydrolytic stability. C1 NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP HURYN, DM (reprint author), HOFFMANN LA ROCHE INC,ROCHE RES CTR,NUTLEY,NJ 07110, USA. OI Huryn, Donna/0000-0001-5542-4968 NR 39 TC 62 Z9 63 U1 1 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 JUN 26 PY 1992 VL 35 IS 13 BP 2347 EP 2354 DI 10.1021/jm00091a001 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JB463 UT WOS:A1992JB46300001 PM 1619614 ER PT J AU CARROLL, FI ABRAHAM, P LEWIN, AH PARHAM, KA BOJA, JW KUHAR, MJ AF CARROLL, FI ABRAHAM, P LEWIN, AH PARHAM, KA BOJA, JW KUHAR, MJ TI ISOPROPYL AND PHENYL-ESTERS OF 3-BETA-(4-SUBSTITUTED PHENYL)TROPAN-2-BETA-CARBOXYLIC ACIDS - POTENT AND SELECTIVE COMPOUNDS FOR THE DOPAMINE TRANSPORTER SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID COCAINE; SEROTONIN; BRAIN C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP CARROLL, FI (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIDA NIH HHS [DA 05477] NR 18 TC 90 Z9 90 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 26 PY 1992 VL 35 IS 13 BP 2497 EP 2500 DI 10.1021/jm00091a019 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JB463 UT WOS:A1992JB46300019 PM 1619622 ER PT J AU WLODAWER, A AF WLODAWER, A TI ANOTHER PIECE OF THE HIV PUZZLE FALLS INTO PLACE SO SCIENCE LA English DT Editorial Material ID PROTEASE RP WLODAWER, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 26 PY 1992 VL 256 IS 5065 BP 1766 EP 1766 DI 10.1126/science.1377402 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA434 UT WOS:A1992JA43400024 PM 1377402 ER PT J AU ANSARI, A JONES, CM HENRY, ER HOFRICHTER, J EATON, WA AF ANSARI, A JONES, CM HENRY, ER HOFRICHTER, J EATON, WA TI THE ROLE OF SOLVENT VISCOSITY IN THE DYNAMICS OF PROTEIN CONFORMATIONAL-CHANGES SO SCIENCE LA English DT Article ID GEMINATE RECOMBINATION; GLASS-TRANSITION; CARBON-MONOXIDE; LIGAND-BINDING; HEME-PROTEINS; MYOGLOBIN; PHOTODISSOCIATION; SPECTROSCOPY; DIFFUSION; KINETICS AB Nanosecond lasers were used to measure the rate of conformational changes ir myoglobin after ligand dissociation at ambient temperatures. At low solvent viscosities the rate is independent of viscosity, but at high viscosities it depends on approximately the inverse first power of the viscosity. Kramers theory for unimolecular rate processes can be used to explain this result if the friction term is modified to include protein as well as solvent friction. The theory and experiment suggest that the dominant factor in markedly reducing the rate of conformational changes in myoglobin at low temperatures (<200 K) is the very high viscosity (>10(7) centipoise) of the glycerol-water solvent. That is, at low temperatures conformational substates may not be "frozen" so much as "stuck." C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 34 TC 395 Z9 400 U1 4 U2 56 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 26 PY 1992 VL 256 IS 5065 BP 1796 EP 1798 DI 10.1126/science.1615323 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA434 UT WOS:A1992JA43400029 PM 1615323 ER PT J AU PIMENTA, PFP TURCO, SJ MCCONVILLE, MJ LAWYER, PG PERKINS, PV SACKS, DL AF PIMENTA, PFP TURCO, SJ MCCONVILLE, MJ LAWYER, PG PERKINS, PV SACKS, DL TI STAGE-SPECIFIC ADHESION OF LEISHMANIA PROMASTIGOTES TO THE SANDFLY MIDGUT SO SCIENCE LA English DT Article ID MAJOR PROMASTIGOTES; TRYPANOSOMA-CRUZI; LIPOPHOSPHOGLYCAN; METACYCLOGENESIS; IDENTIFICATION; GLYCOCONJUGATE; ATTACHMENT; GUT AB Although leishmaniasis is transmitted to humans almost exclusively by the bite of infected phlebotomine sandflies, little is known about the molecules controlling the survival and development of Leishmania parasites in their insect vectors. Adhesion of Leishmania promastigotes to the midgut epithelial cells of the sandfly was found to be an inherent property of noninfective-stage promastigotes, which was lost during their transformation to metacyclic forms, thus permitting the selective release of infective-stage parasites for subsequent transmission by bite. Midgut attachment and release was found to be controlled by specific developmental modifications in terminally exposed saccharides on lipophosphoglycan, the major surface molecule on Leishmania promastigotes. C1 NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT ENTOMOL,WASHINGTON,DC 20307. UNIV KENTUCKY,MED CTR,DEPT BIOCHEM,LEXINGTON,KY 40536. UNIV DUNDEE,DEPT BIOCHEM,DUNDEE DD1 4HN,SCOTLAND. NR 26 TC 178 Z9 180 U1 0 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 26 PY 1992 VL 256 IS 5065 BP 1812 EP 1815 DI 10.1126/science.1615326 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA434 UT WOS:A1992JA43400034 PM 1615326 ER PT J AU HUNT, DF MICHEL, H DICKINSON, TA SHABANOWITZ, J COX, AL SAKAGUCHI, K APPELLA, E GREY, HM SETTE, A AF HUNT, DF MICHEL, H DICKINSON, TA SHABANOWITZ, J COX, AL SAKAGUCHI, K APPELLA, E GREY, HM SETTE, A TI PEPTIDES PRESENTED TO THE IMMUNE-SYSTEM BY THE MURINE CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE-I-A(D) SO SCIENCE LA English DT Article ID MHC CLASS; PROTEIN ANTIGENS; BINDING PEPTIDES; SEQUENCE AB Between 650 and 2000 different peptides are associated with the major histocompatibility complex class II molecule I-A(d). Sequences for nine of these were obtained by a combination of automated Edman degradation and tandem mass spectrometry. All of the peptides are derived from secretory or integral membrane proteins that are synthesized by the antigen-presenting cell itself. Peptides were 16 to 18 residues long, had ragged NH2- and COOH-termini, and contained a six-residue binding motif that was variably placed within the peptide chain. Binding data on truncated peptides suggest that the peptide binding groove on class II molecules can be open at both ends. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. CYTEL CORP,SAN DIEGO,CA 92121. RP HUNT, DF (reprint author), UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22901, USA. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NIAID NIH HHS [AI18634]; NIGMS NIH HHS [GM37357] NR 28 TC 631 Z9 636 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 26 PY 1992 VL 256 IS 5065 BP 1817 EP 1820 DI 10.1126/science.1319610 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA434 UT WOS:A1992JA43400036 PM 1319610 ER PT J AU RHEE, SG CHOI, KD AF RHEE, SG CHOI, KD TI REGULATION OF INOSITOL PHOSPHOLIPID-SPECIFIC PHOSPHOLIPASE-C ISOZYMES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID EPIDERMAL GROWTH-FACTOR; PROTEIN; BETA RP RHEE, SG (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,RM 122,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 731 Z9 734 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 12393 EP 12396 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300001 PM 1319994 ER PT J AU KOUNNAS, MZ MORRIS, RE THOMPSON, MR FITZGERALD, DJ STRICKLAND, DK SAELINGER, CB AF KOUNNAS, MZ MORRIS, RE THOMPSON, MR FITZGERALD, DJ STRICKLAND, DK SAELINGER, CB TI THE ALPHA-2-MACROGLOBULIN RECEPTOR LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN BINDS AND INTERNALIZES PSEUDOMONAS EXOTOXIN-A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID LDL-RECEPTOR; CULTURED FIBROBLASTS; ESCHERICHIA-COLI; APOLIPOPROTEIN-E; PLASMA-MEMBRANE; MAMMALIAN-CELLS; DOMAIN-I; AERUGINOSA; TOXIN; SEQUENCE AB The alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha-2MR/LRP) is a large cell-surface glycoprotein consisting of a 515-kDa and an 85-kDa polypeptide; this receptor is thought to be responsible for the binding and endocytosis of activated alpha-2-macroglobulin and apoE-enriched beta-very low density lipoprotein. A similar high molecular weight glycoprotein has been identified as a potential receptor for Pseudomonas exotoxin A (PE). We demonstrate that the alpha-2MR/LRP and the PE-binding glycoprotein have a similar mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and are immunologically indistinguishable. Furthermore, affinity-purified alpha-2MR/LRP binds specifically to PE but not to a mutant toxin defective in its ability to bind cells. The 39-kDa receptor-associated protein, which blocks binding of ligands to alpha-2MR/LRP, also prevents binding and subsequent toxicity of PE for mouse fibroblasts. The concentration of receptor-associated protein that was required to reduce binding and toxicity to 50% was approximately 14 nM, a value virtually identical to the, K(D) measured for the interaction of receptor-associated protein with the purified receptor. Overall, the studies strongly suggest that the alpha-2MR/LRP is responsible for internalizing PE. C1 UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. AMER RED CROSS,BIOCHEM LAB,ROCKVILLE,MD 20855. UNIV CINCINNATI,COLL MED,DEPT ANAT & CELL BIOL,CINCINNATI,OH 45267. UNIV CINCINNATI,COLL MED,DIV DIGEST DIS,CINCINNATI,OH 45267. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL30200/ +]; NIAID NIH HHS [AI17529]; NIGMS NIH HHS [GM42581] NR 47 TC 382 Z9 390 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 12420 EP 12423 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300008 PM 1618748 ER PT J AU KUSTER, H ZHANG, L BRINI, AT MACGLASHAN, DWJ KINET, JP AF KUSTER, H ZHANG, L BRINI, AT MACGLASHAN, DWJ KINET, JP TI THE GENE AND CDNA FOR THE HUMAN HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTOR BETA-CHAIN AND EXPRESSION OF THE COMPLETE HUMAN RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAST-CELL RECEPTOR; IGE RECEPTOR; TRANSFECTED CELLS; ALPHA-SUBUNIT; SURFACE EXPRESSION; MOUSE CHROMOSOME-1; GAMMA-SUBUNIT; FC-GAMMA; FAMILY AB The high affinity IgE receptor (Fc-epsilon-RI) is a tetrameric hetero-oligomer composed of an alpha-chain, a beta-chain, and two disulfide-linked gamma-chains. The beta-chain contains four transmembrane (TM) segments and long cytoplasmic domains that are thought to play an important role in intracellular signaling. We now report the structural characterization and the sequence of the complete human beta-gene and cDNA. The gene spans approximately 10 kilobases and contains seven exons. There is a single transcription initiation site preceded by a TATA box. The first exon codes for the 5'-untranslated region and a portion of the N-terminal cytoplasmic tail. TM-1 is encoded in exons 2 and 3, TM-2 in exons 3 and 4, TM-3 in exon 5, and TM-4 in exon 6. The seventh and final exon encodes the end of the C-terminal cytoplasmic tail and the 3'-untranslated sequence. The human beta-gene appears to be a single copy gene. Two corresponding transcripts, detected as a doublet around 3.9 kilobases, are present in cells of mast cell and basophil lineage from different individuals, but not in the other hematopoietic cells tested here. The human beta-protein is homologous to rodent-beta. The consensus amino acid sequences of human, mouse, and rat-beta show 69% identical residues. Analysis of the surface expression of transfected receptors indicates that human alpha-gamma and alpha-beta-gamma complexes are expressed with comparable efficiency. Human-beta interacts with human-alpha more efficiently than does rat-beta, and both rat and mouse-beta interact with their corresponding alpha more efficiently than does human-beta, demonstrating a species specificity of the alpha/beta interaction. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,TWINBROOK II BLDG,12441 PARKLAWN DR,ROCKVILLE,MD 20852. JOHNS HOPKINS UNIV,CTR ASTHMA & ALLERGY,BALTIMORE,MD 21224. NR 25 TC 78 Z9 79 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 12782 EP 12787 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300061 PM 1535625 ER PT J AU DING, RC POMMIER, Y KANG, VH SMULSON, M AF DING, RC POMMIER, Y KANG, VH SMULSON, M TI DEPLETION OF POLY(ADP-RIBOSE) POLYMERASE BY ANTISENSE RNA EXPRESSION RESULTS IN A DELAY IN DNA STRAND BREAK REJOINING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTI-SENSE RNA; POLY(ADENOSINE DIPHOSPHATE RIBOSE); NUCLEAR-PROTEIN MODIFICATION; MAMMALIAN-CELLS; EXCISION REPAIR; GENE-EXPRESSION; CHROMATIN; GROWTH; DIFFERENTIATION; ONCOGENE AB The effects of inducible expression of poly(ADP-ribose) polymerase (PADPRP) antisense RNA in HeLa cells were determined in order to gain further insight into the biological roles of the poly(ADP-ribosyl)ation modification of nuclear proteins. A recombinant expression plasmid was prepared with the mouse mammary tumor virus (MMTV) promoter upstream of the antisense-oriented PADPRP cDNA. Expression of the antisense RNA was under strict control, with negligible effects on cell growth being apparent in the absence of inducer. Consistent with the previously described stability of PADPRP (half-life of at least 2 days, in vivo), 48-72 h were required after induction of antisense RNA expression by dexamethasone for the abundant concentration of PADPRP, normally present in HeLa cells, to be reduced by greater than 80%. The depletion of endogenous PADPRP as mediated by induced antisense RNA expression was established by: (i) a progressive synthesis of antisense transcripts in cells as assessed by Northern analysis; (ii) an 80% decrease in activity of the enzyme; and (iii) a greater than 90% reduction in the cellular content of PADPRP protein, as demonstrated by both immunoblotting and immunohistochemical analysis in intact cells. Several biological parameters were monitored in cells depleted of PADPRP. The chromatin of PADPRP-depleted cells was shown to have an altered structure as assessed by deoxyribonuclease I susceptibility. Cell morphology was also altered, with multinucleated aggregates being evident 72 h after induction of antisense RNA expression. Cells depleted of PADPRP were not able to commence DNA strand break joining of damaged DNA. However, DNA repair capacity was re-established at later time periods, indicating that PADPRP may contribute to alterations in chromatin structure that occur initially in DNA strand break rejoining and that the concentration of the enzyme in nuclei exceeds the requirement for DNA repair/replication. C1 GEORGETOWN UNIV, DEPT BIOCHEM & MOLEC BIOL, 3900 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. NCI, MOLEC PHARMACOL LAB, BALTIMORE, MD 21201 USA. FU NCI NIH HHS [CA25344] NR 49 TC 138 Z9 146 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 12804 EP 12812 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300064 PM 1618781 ER PT J AU BONNER, JC GOODELL, AL LASKY, JA HOFFMAN, MR AF BONNER, JC GOODELL, AL LASKY, JA HOFFMAN, MR TI REVERSIBLE BINDING OF PLATELET-DERIVED GROWTH FACTOR-AA, FACTOR-AB, AND FACTOR-BB ISOFORMS TO A SIMILAR SITE ON THE SLOW AND FAST CONFORMATIONS OF ALPHA-2-MACROGLOBULIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IDIOPATHIC PULMONARY FIBROSIS; ALPHA-MACROGLOBULIN; ALVEOLAR MACROPHAGES; HUMAN-FIBROBLASTS; FACTOR-BETA; PROTEASE COMPLEXES; SURFACE-RECEPTORS; FAST FORMS; PDGF; CELLS AB The mechanism by which the platelet-derived growth factor (PDGF)-binding protein, alpha-2-macroglobulin (alpha-2M), modulates PDGF bioactivity is unknown, but could involve reversible PDGF-alpha-2M binding. Herein we report that >70% of I-125-PDGF-BB or -AB complexed to alpha-2M was dissociated by SDS-denaturation followed by SDS-polyacrylamide gel electrophoresis, i.e. most of the binding was noncovalent. Reduction of the PDGF.alpha-2M complex following denaturation dissociated the cytokine from alpha-2M by >90%, suggesting covalent disulfide bond formation. Approximately 50% of the growth factor was dissociated by lowering the pH from 7.5 to 4.0. I-125-PDGF-BB bound alpha-2M in a time-dependent manner (t1/2 = approximately 1 h), reaching equilibrium after 4 h. The I-125-pDGF.BB/alpha-2M complex dissociated more slowly (t1/2 = approximately 2.5 h). "Slow" and "fast" alpha-2M bound nearly equal amounts of PDGF-AB or -BB. Trypsin treatment converted PDGF-BB/alpha-2M complex to the fast conformation but did not release bound I-125-PDGF-BB. All PDGF-isoforms (AA, -AB, and -BB) competed for binding with I-125-PDGF-BB binding to slow alpha-2M and fast alpha-2M-methylamine by 65-80%. Other cytokines that bind alpha-2M (transforming growth factor-beta-1 and -beta-2, tumor necrosis factor-alpha, basic fibroblast growth factor, interleukin-1-beta, and -6) did not compete for I-125-PDGF-BB binding slow alpha-2M, but transforming growth factor-beta-1 and basic fibroblast growth factor inhibited I-125-PDGF-BB binding alpha-2M-methylamine by 30-50%. The reversible nature of the PDGF.alpha-2M complex could allow for targeted PDGF release near mesenchymal cells which possess PDGF receptors. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. RP BONNER, JC (reprint author), NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 54 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 12837 EP 12844 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300069 PM 1377675 ER PT J AU LEE, SW KAHN, ML DICHEK, DA AF LEE, SW KAHN, ML DICHEK, DA TI EXPRESSION OF AN ANCHORED UROKINASE IN THE APICAL ENDOTHELIAL-CELL MEMBRANE - PRESERVATION OF ENZYMATIC-ACTIVITY AND ENHANCEMENT OF CELL-SURFACE PLASMINOGEN ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-TRANSFER; ARTERIAL-WALL; TISSUE-TYPE; LINE; IDENTIFICATION; ATTACHMENT; RECEPTORS; MECHANISM; PROTEINS; BINDING AB A mutant single chain urokinase plasminogen activator (scu-PA) was constructed by the addition of an apical membrane targeting signal from decay accelerating factor to the scu-PA carboxyl terminus. Bovine aortic endothelial cells (EC) were transduced with the mutant scu-PA. Metabolic labeling, immunoprecipitation, and gel electrophoresis revealed that the mutant scu-PA was present in a single-chain form at the EC surface. Immunohistochemistry and enzyme-linked immunosorbent assay before and after treatment of EC with phosphotidylinositol-specific phospholipase C confirmed that scu-PA was attached to the EC surface by a glycosyl-phosphotidylinositol anchor. Approximately 10(6) anchored scu-PA molecules/cell were present; however, anchoring was not 100% efficient, with scu-PA released into the medium as well. Selective biotinylation of the apical and basolateral surfaces revealed that anchored scu-PA was polarized to the apical surface. Apically anchored scu-PA could be converted by plasmin to two-chain urokinase, with a normal specific activity (140,000 IU/mg) as measured with the chromogenic substrate S-2444. Expression of anchored scu-PA resulted in an increase in EC surface plasminogen activator activity, as compared with the activity of either untransduced EC or EC transduced with a wild type scu-PA. These experiments demonstrate: 1) apical membrane targeting can be accomplished in EC; 2) scu-PA can be anchored to the EC surface with preservation of enzymatic activity; 3) EC surface plasminogen activator activity is significantly increased by the presence of anchored scu-PA. Cell surface targeted plasminogen activators may eventually be useful in the prevention and treatment of intravascular thrombosis. C1 NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,RM 7D-18,BETHESDA,MD 20892. NR 50 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 13020 EP 13027 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300093 PM 1535628 ER PT J AU BRZOVIC, PS SAWA, Y HYDE, CC MILES, EW DUNN, MF AF BRZOVIC, PS SAWA, Y HYDE, CC MILES, EW DUNN, MF TI EVIDENCE THAT MUTATIONS IN A LOOP REGION OF THE ALPHA-SUBUNIT INHIBIT THE TRANSITION FROM AN OPEN TO A CLOSED CONFORMATION IN THE TRYPTOPHAN SYNTHASE BIENZYME COMPLEX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; ESCHERICHIA-COLI; L-SERINE; SALMONELLA-TYPHIMURIUM; BETA-SUBUNIT; TRIOSEPHOSPHATE ISOMERASE; 3-DIMENSIONAL STRUCTURE; CATALYTIC MECHANISM; MULTIENZYME COMPLEX; SECONDARY STRUCTURE AB Rapid-scanning stopped-flow (RSSF) UV-visible spectroscopy has been used to investigate the effects of single amino acid mutations in the alpha-subunit of the Salmonella typhimurium tryptophan synthase bienzyme complex on the reactivity at the beta-subunit active site located 25 to 30 angstrom distant. The pyridoxal 5'-phosphate (PLP) cofactor provides a convenient spectroscopic probe to directly monitor catalytic events at the beta-active site. Single substitutions of Phe for Glu at position 49, Leu for Gly at position 51, or Tyr for Asp at position 60 in the alpha-subunit strongly alter the observed steady state and pre-steady state inhibitory effects of the alpha-subunit-specific ligand alpha-glycerophosphate (GP) on the PLP-dependent beta-reaction. However, similar GP-induced allosteric effects on the distribution of covalent intermediates bound at the beta-site that are observed with the wild-type enzyme (Houben, K. F., and Dunn, M. F. (1990) Biochemistry 29, 2421-2429) also are observed for each of the mutant bienzyme complexes. These results support the hypothesis that the preferred pathway of indole from solution into the beta-site is via the a-site and the interconnecting tunnel (Dunn, M. F., Aguilar, V., Brzovic', P., Drewe, W. F., Houben, K. F., Leja, C. A., and Roy, M. (1990) Biochemistry 29, 8598-8607). Residues alpha-E49, alpha-G51, and alpha-D60 are part of a highly conserved inserted sequence in the alpha/beta-barrel topology of the alpha-subunit. We propose that the GP-induced inhibition of the beta-reaction results, in part, from a ligand-dependent conformational change from an "open" to a "closed" structure of the alpha-subunit which involves this region of the alpha-subunit and serves to obstruct the direct access of indole into the tunnel. Our findings suggest that the altered kinetic behavior observed for the alpha-mutants in the presence of GP reflects an impaired ability of the modified bienzyme complex to undergo the conformational transition from the open to the closed form. C1 UNIV CALIF RIVERSIDE, DEPT BIOCHEM, RIVERSIDE, CA 92521 USA. NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 48 TC 66 Z9 66 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 13028 EP 13038 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300094 PM 1618800 ER PT J AU KAHN, RA RANDAZZO, P SERAFINI, T WEISS, O RULKA, C CLARK, J AMHERDT, M ROLLER, P ORCI, L ROTHMAN, JE AF KAHN, RA RANDAZZO, P SERAFINI, T WEISS, O RULKA, C CLARK, J AMHERDT, M ROLLER, P ORCI, L ROTHMAN, JE TI THE AMINO TERMINUS OF ADP-RIBOSYLATION FACTOR (ARF) IS A CRITICAL DETERMINANT OF ARF ACTIVITIES AND IS A POTENT AND SPECIFIC INHIBITOR OF PROTEIN-TRANSPORT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GOLGI STACK; ADENYLATE-CYCLASE; CHOLERA-TOXIN; REGULATORY COMPONENT; VESICULAR TRANSPORT; RNA-POLYMERASE; BOVINE BRAIN; BINDING; PURIFICATION; EXPRESSION AB Deletion of the amino-terminal 17 residues from human ADP-ribosylation factor (ARF) resulted in a protein ([DELTA-1-17]mARF1p) devoid of ARF activity but which retained the ability to bind guanine nucleotides with high affinity. Unlike the wild type, the binding of guanine nucleotides to this deletion mutant was found to be independent of added phospholipids. A chimeric protein was produced, consisting of 10% (the amino-terminal 17 amino acids) human ARF1p and 90% ARL1p, an ARF-like protein (55% identical protein sequence) from Drosophila. This chimera was found to have ARF activity, lacking in the parental ARL1 protein. Thus, the amino terminus of ARF1p was shown to be a critical component of ARF activity. A synthetic peptide, derived from the amino terminus of ARF1p, has no ARF activity. Rather, the peptide was found to be a specific inhibitor of ARF activities. This peptide was also found to be a potent and specific inhibitor of both an in vitro intra-Golgi transport assay and the guanosine 5'-3-O-(thio)triphosphate-stimulated accumulation of coated vesicles and buds from Golgi preparations. We conclude that ARF is required for the budding of coated vesicles from the Golgi stacks and serves a regulatory role in protein secretion through the Golgi in eukaryotic cells. C1 NCI, DIV CANC TREATMENT, MEDICINAL CHEM LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. PRINCETON UNIV, DEPT BIOL, PRINCETON, NJ 08544 USA. UNIV GENEVA, INST HISTOL & EMBRYOL, DEPT MORPHOL, CH-1211 GENEVA 4, SWITZERLAND. RP NCI, BIOL CHEM LAB, BETHESDA, MD 20892 USA. NR 33 TC 230 Z9 233 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 13039 EP 13046 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300095 PM 1618801 ER PT J AU LENHARD, JM KAHN, RA STAHL, PD AF LENHARD, JM KAHN, RA STAHL, PD TI EVIDENCE FOR ADP-RIBOSYLATION FACTOR (ARF) AS A REGULATOR OF INVITRO ENDOSOME-ENDOSOME FUSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENYLATE-CYCLASE; G-PROTEINS; BINDING; TRANSPORT AB We have used an in vitro endosome fusion assay, recombinant ARF, synthetic peptides, and guanosine 5'-3-O-(thio)triphosphate (GTP-gamma-S) to study the role of ARF during endocytosis. Previous work has shown that GTP-gamma-S stimulates in vitro endosome fusion in dilute cytosol (<0.5 mg/ml) but inhibits fusion in concentrated cytosol (>1.0 mg/ml). Two peptides corresponding to the NH2-terminal 16 amino acids of human ARF1 and ARF4 blocked GTP-gamma-S stimulation of fusion in dilute cytosol and reversed GTP-gamma-S inhibition of fusion in concentrated cytosol. The addition of recombinant human ARF1 to endosomes in dilute or concentrated cytosol resulted in GTP-gamma-S-dependent inhibition of fusion. Only the myristoylated form of ARF inhibited fusion. The NH2-terminal ARF1 peptide reversed inhibition by recombinant ARF1. Preincubation experiments showed that endosomes could form an ARF-resistant intermediate during the fusion process. Western blot analysis revealed clathrin-coated vesicles extracted with detergent retained ARF. The results suggest that ARF is involved in both the stimulatory and inhibitory effects of GTP-gamma-S in dilute and concentrated cytosol, respectively. Furthermore, myristoylation, the NH2-terminal domain, and binding to GTP appear to be critical for ARF activity during an early prefusion step required for endocytosis. C1 WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,660 S EUCLID,ST LOUIS,MO 63110. NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RI Stahl, Philip/D-6315-2012 FU NIAID NIH HHS [AI20015]; NIGMS NIH HHS [GM42259] NR 25 TC 176 Z9 176 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 13047 EP 13052 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300096 PM 1618802 ER PT J AU BALCH, WE KAHN, RA SCHWANINGER, R AF BALCH, WE KAHN, RA SCHWANINGER, R TI ADP-RIBOSYLATION FACTOR IS REQUIRED FOR VESICULAR TRAFFICKING BETWEEN THE ENDOPLASMIC-RETICULUM AND THE CIS-GOLGI COMPARTMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING-PROTEIN; YPT1 GENE-PRODUCT; SECRETORY PATHWAY; EUKARYOTIC PROTEIN; ADENYLATE-CYCLASE; CHOLERA-TOXIN; BREFELDIN-A; YEAST YPT1; TRANSPORT; APPARATUS AB We describe the potential role of ADP-ribosylation factor (ARF) in vesicular trafficking using an in vitro assay that efficiently reconstitutes transport between the endoplasmic reticulum (ER) and the cis-Golgi compartment in mammalian semi-intact cells, a population of cells in which the plasma membrane is physically perforated to reveal intact ER and Golgi compartments. We demonstrate that peptides identical to the amino-terminal domain of ARF, which inhibit ARF cofactor activity in cholera toxin-catalyzed ADP-ribosylation of G(alpha-s) (Kahn, R. A., Randazzo, P., Serafini, T., Weiss, O., Rulka, C., Clark, J., Amherdt, M., Roller, P., Orci, L., and Rothman, J. E. (1992) J. Biol. Chem. 267, 13039-13046), inhibit transport of the vesicular stomatitis virus G protein between the ER and cis-Golgi compartment. Inhibition of transport was rapid (t1/2 = 30-60 s) and irreversible. Half-maximal inhibition was observed at concentrations of 15 and 22-mu-M with peptides identical to the amino-terminal domain of the human ARF4 (hARF4) protein and the human ARF1 protein, respectively. Kinetic analysis of vesicular stomatitis virus G protein transport suggested that the hARF4 peptide inhibits a late vesicle fusion step. In addition, incubation of semi-intact cells in the presence of the myristoylated form human ARF1 (hARF1myr) protein, but not the nonmyristoylated form of ARF1, inhibited transport. In contrast to peptide, the hARF1myr blocked an early transport step, similar to that observed with guanosine 5'-3-O-(thio)triphosphate. These results suggest that ARF and components facilitating ARF function play an important role in the cyclical fission and fusion of transport vesicles mediating ER to Golgi trafficking. C1 SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. NCI, DIV CANC TREATMENT, BIOL CHEM LAB, BETHESDA, MD 20892 USA. RP BALCH, WE (reprint author), SCRIPPS RES INST, DEPT CELLULAR BIOL, LA JOLLA, CA 92037 USA. FU NCI NIH HHS [CA 27489]; NIGMS NIH HHS [GM 42336, GM33301] NR 66 TC 192 Z9 192 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1992 VL 267 IS 18 BP 13053 EP 13061 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ483 UT WOS:A1992HZ48300097 PM 1618803 ER PT J AU OKEEFE, SJ TAMURA, J KINCAID, RL TOCCI, MJ ONEILL, EA AF OKEEFE, SJ TAMURA, J KINCAID, RL TOCCI, MJ ONEILL, EA TI FK-506-SENSITIVE AND CSA-SENSITIVE ACTIVATION OF THE INTERLEUKIN-2 PROMOTER BY CALCINEURIN SO NATURE LA English DT Article ID EXPRESSION; CALMODULIN; DOMAIN; CELLS AB ANTIGEN recognition by the T-cell receptor (TCR) initiates events including lymphokine gene transcription 1, particularly interleukin-2, that lead to T-cell activation. The immunosuppressive drugs, cyclosporin A (CsA) and FK-506, prevent T-cell proliferation by inhibiting a Ca2+-dependent event required for induction of interleukin-2 transcription 2. Complexes of FK-506 or CsA and their respective intracellular binding proteins inhibit the calmodulin-dependent protein phosphatase, calcineurin, in vitro 3. The pharmacological relevance of this observation to immunosuppression or drug toxicity is undetermined. Calcineurin, although present in lymphocytes 4, has not been implicated in TCR-mediated activation of lymphokine genes or in transcriptional regulation in general. Here we report that transfection of a calcineurin catalytic subunit increases the 50% inhibitory concentration (IC50) of the immunosuppressants FK-506 and CsA, and that a mutant subunit acts in synergy with phorbol ester alone to activate the interleukin-2 promoter in a drug-sensitive manner. These results implicate calcineurin as a component of the TCR signal transduction pathway by demonstrating its role in the drug-sensitive activation of the interleukin-2 promoter. C1 NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,IMMUNOL SECT,ROCKVILLE,MD 20852. RP OKEEFE, SJ (reprint author), MERCK SHARP & DOHME LTD,DEPT MOLEC IMMUNOL,RAHWAY,NJ 07065, USA. NR 19 TC 809 Z9 821 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 25 PY 1992 VL 357 IS 6380 BP 692 EP 694 DI 10.1038/357692a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA430 UT WOS:A1992JA43000072 PM 1377361 ER PT J AU MALNATI, MS MARTI, M LAVAUTE, T JARAQUEMADA, D BIDDISON, W DEMARS, R LONG, EO AF MALNATI, MS MARTI, M LAVAUTE, T JARAQUEMADA, D BIDDISON, W DEMARS, R LONG, EO TI PROCESSING PATHWAYS FOR PRESENTATION OF CYTOSOLIC ANTIGEN TO MHC CLASS-II-RESTRICTED T-CELLS SO NATURE LA English DT Article ID TOXIC LYMPHOCYTES-T; LYMPHOBLASTOID-CELLS; EXPRESSION; REGION; HEMAGGLUTININ; TRANSPORTERS; RECOGNITION; SEQUENCES AB ANTIGENS presented to CD4+ T cells derive primarily from exogenous proteins that are processed into peptides capable of binding to class II major histocompatibility complex (MHC) molecules in an endocytic compartment 1-4. In contrast, antigens presented to CD8+ T cells derive mostly from proteins processed in the cytosol, and peptide loading onto class I MHC molecules in an early exocytic compartment is dependent on a transporter for antigen presentation encoded in the class II MHC region 5-11. Endogenous cytosolic antigen can also be presented by class II molecules 12,13. Here we show that, unlike class I-restricted recognition of antigen, HLA-DR1-restricted recognition of cytosolic antigen occurs in mutant cells without a transporter for antigen presentation. In contrast, DR1-restricted recognition of a short cytosolic peptide is dependent on such a transporter. Thus helper T-cell epitopes can be generated from cytosolic antigens by several mechanisms, one of which is distinct from the classical class I pathway. C1 NIAID,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852. HOSP GERMANS TRIAS & PUJOL,IMMUNOL UNIT,E-08916 BADALONA,SPAIN. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 28 TC 178 Z9 178 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 25 PY 1992 VL 357 IS 6380 BP 702 EP 704 DI 10.1038/357702a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA430 UT WOS:A1992JA43000076 PM 1614517 ER PT J AU CURTIS, RE BOICE, JD STOVALL, M BERNSTEIN, L GREENBERG, RS FLANNERY, JT SCHWARTZ, AG WEYER, P MOLONEY, WC HOOVER, RN AF CURTIS, RE BOICE, JD STOVALL, M BERNSTEIN, L GREENBERG, RS FLANNERY, JT SCHWARTZ, AG WEYER, P MOLONEY, WC HOOVER, RN TI RISK OF LEUKEMIA AFTER CHEMOTHERAPY AND RADIATION TREATMENT FOR BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HODGKINS-DISEASE; ADJUVANT CHEMOTHERAPY; OVARIAN-CANCER; CYCLOPHOSPHAMIDE; RADIOTHERAPY; MALIGNANCIES; MELPHALAN; NEOPLASMS; CERVIX AB Background. Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail. Methods. We conducted a case-control study in a cohort of 82,700 women given a diagnosis of breast cancer from 1973 to 1985 in five areas of the United States. Detailed information about therapy was obtained for 90 patients with leukemia and 264 matched controls. The dose of radiation to the active marrow was estimated from individual radiotherapy records (mean dose, 7.5 Gy). Results. The risk of acute nonlymphocytic leukemia was significantly increased after regional radiotherapy alone (relative risk, 2.4), alkylating agents alone (relative risk, 10.0), and combined radiation and drug therapy (relative risk, 17.4). Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide. Melphalan was 10 times more leukemogenic than cyclophosphamide (relative risk, 31.4 vs. 3.1). There was little increase in the risk associated with total cyclophosphamide doses of less than 20,000 mg. Conclusions. Although leukemia occurs in few patients with breast cancer, significantly elevated risks were linked to treatments with regional radiation and alkylating agents. Melphalan is a more potent leukemogen than cyclophosphamide or radiotherapy. Low risks were associated with the levels of cyclophosphamide in common use today. Systemic drug therapy combined with radiotherapy that delivers high doses to the marrow appears to enhance the risk of leukemia. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIAT PHYS,HOUSTON,TX 77025. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. EMORY UNIV,SCH PUBL HLTH,ATLANTA,GA 30322. DEPT HLTH SERV,CONNECTICUT TUMOR REGISTRY,HARTFORD,CT. MICHIGAN CANC FDN,DETROIT,MI 48201. STATE HLTH REGISTRY IOWA,IOWA CITY,IA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CURTIS, RE (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 23 TC 270 Z9 274 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 25 PY 1992 VL 326 IS 26 BP 1745 EP 1751 DI 10.1056/NEJM199206253262605 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA HZ894 UT WOS:A1992HZ89400005 PM 1594016 ER PT J AU DOPPMAN, JL AF DOPPMAN, JL TI PANCREATIC ENDOCRINE TUMORS - THE SEARCH GOES ON SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LOCALIZATION; GASTRINOMAS; INJECTION; SECRETIN RP DOPPMAN, JL (reprint author), NIH,BETHESDA,MD 20892, USA. NR 10 TC 32 Z9 32 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 25 PY 1992 VL 326 IS 26 BP 1770 EP 1772 DI 10.1056/NEJM199206253262609 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA HZ894 UT WOS:A1992HZ89400009 PM 1317507 ER PT J AU YOSHIMURA, K ROSENFELD, MA NAKAMURA, H SCHERER, EM PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF YOSHIMURA, K ROSENFELD, MA NAKAMURA, H SCHERER, EM PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI EXPRESSION OF THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE IN THE MOUSE LUNG AFTER INVIVO INTRATRACHEAL PLASMID-MEDIATED GENE-TRANSFER SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; MAMMALIAN-CELLS; CHLORIDE CHANNELS; ESCHERICHIA-COLI; DNA; IDENTIFICATION; RETROVIRUS; MUTATIONS; FRAGMENTS; BINDING AB As an approach to gene therapy for the respiratory manifestations of cystic fibrosis (CF), in vivo plasmid-mediated direct transfer of the normal CF transmembrane conductance regulator (CFTR) gene to the airway epithelium was investigated in mice. To evaluate the feasibility of this strategy, pRSVL, a plasmid composed of a firefly luciferase gene driven by the Rous sarcoma virus long terminal repeat (RSV-LTR), along with cationic liposomes was instilled into the trachea of C57BI/6NCR mice. With administration of 200 - 400-mu-g plasmid DNA, luciferase expression could be detected in the mouse lung homogenates for at least 4 wk. With this background, a CFTR expression plasmid vector (pRSVCFTR) constructed by replacing the luciferase cDNA from pRSVL with the normal human CFTR cDNA was evaluated in vivo in mice. Intratracheal instillation of pRSVCFTR with cationic liposomes followed by analysis of mouse lung RNA by polymerase chain reaction amplification (after conversion of mRNA to cDNA) using a RSV-LTR specific sense primer and a human CFTR-specific antisense primer demonstrated human CFTR mRNA transcripts from one day to 4 wk after instillation. Further, in vivo evaluation of beta-galactosidase activity after intratracheal administration of an E. coli lacZ gene expression plasmid vector directed by the cytomegalovirus promoter (pCMV-beta) demonstrated that the airway epithelium was the major target of transfer and expression of the exogenous gene. These observations demonstrate successful plasmid-mediated gene transfer to the airway epithelium in vivo. This strategy may be feasible as a form of gene therapy to prevent the pulmonary manifestations of CF. C1 TRANSGENE SA,F-67000 STRASBOURG,FRANCE. RP YOSHIMURA, K (reprint author), NHLBI,PULM BRANCH,BETHESDA,MD 20892, USA. NR 54 TC 156 Z9 158 U1 0 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 25 PY 1992 VL 20 IS 12 BP 3233 EP 3240 DI 10.1093/nar/20.12.3233 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC850 UT WOS:A1992JC85000045 PM 1377820 ER PT J AU REMINGTON, MP HOFFMAN, PM RUSCETTI, SK MASUDA, M AF REMINGTON, MP HOFFMAN, PM RUSCETTI, SK MASUDA, M TI COMPLETE NUCLEOTIDE-SEQUENCE OF A NEUROPATHOGENIC VARIANT OF FRIEND MURINE LEUKEMIA-VIRUS PVC-211 SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. VET ADM MED CTR,RETROVIRUS RES CTR,BALTIMORE,MD 21218. NR 7 TC 16 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 25 PY 1992 VL 20 IS 12 BP 3249 EP 3249 DI 10.1093/nar/20.12.3249 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JC850 UT WOS:A1992JC85000047 PM 1620621 ER PT J AU PIERCE, JP GILPIN, E BURNS, DM SHOPLAND, D JOHNSON, M AF PIERCE, JP GILPIN, E BURNS, DM SHOPLAND, D JOHNSON, M TI TOBACCO - PROMOTION AND SMOKING - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI,BETHESDA,MD 20892. CALIF DEPT HLTH,SACRAMENTO,CA. RP PIERCE, JP (reprint author), UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093, USA. NR 8 TC 1 Z9 1 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 JUN 24 PY 1992 VL 267 IS 24 BP 3283 EP 3284 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HY944 UT WOS:A1992HY94400013 ER PT J AU HADORN, DC MCCORMICK, K DIOKNO, A AF HADORN, DC MCCORMICK, K DIOKNO, A TI AN ANNOTATED ALGORITHM APPROACH TO CLINICAL GUIDELINE DEVELOPMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PATIENT-CARE; MEDICINE AB The Urinary Incontinence in Adults Guideline Panel facilitated the ready elucidation of its guideline's management recommendations through the use of an annotated algorithm approach. The algorithms created as part of this guideline differ from previous algorithms in two ways: (1) they employ systematic annotation to link explicitly the algorithms' recommendations to the literature, and (2) they contain patient counseling and decision nodes to depict the major preference-dependent decision or branch points in the algorithm. We believe that these two innovations can help ensure the clinical validity of guidelines' algorithms while preserving appropriate clinical flexibility and respecting patient preferences. C1 WILLIAM BEAUMONT HOSP,ROYAL OAK,MI 48072. RAND CORP,SANTA MONICA,CA 90406. NIA,GERIATR RES CTR,BETHESDA,MD 20892. FU AHRQ HHS [T32 HS 00007] NR 13 TC 41 Z9 41 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 24 PY 1992 VL 267 IS 24 BP 3311 EP 3314 DI 10.1001/jama.267.24.3311 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA HY944 UT WOS:A1992HY94400030 PM 1597913 ER PT J AU BAI, R FRIEDMAN, SJ PETTIT, GR HAMEL, E AF BAI, R FRIEDMAN, SJ PETTIT, GR HAMEL, E TI DOLASTATIN-15, A POTENT ANTIMITOTIC DEPSIPEPTIDE DERIVED FROM DOLABELLA-AURICULARIA - INTERACTION WITH TUBULIN AND EFFECTS ON CELLULAR MICROTUBULES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ANTINEOPLASTIC AGENTS; THIOCOLCHICINE; NUCLEOTIDE; PROTEINS; BINDING AB Dolastatin 15, a seven-subunit depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent dolastatin 10, a five-subunit peptide obtained from the same organism. We have compared dolastatin 15 with dolastatin 10 for its effects on cells grown in culture and on biochemical properties of tubulin. The IC50 values for cell growth were obtained for dolastatin 15 with L1210 murine leukemia cells, human Burkitt lymphoma cells, and Chinese hamster ovary (CHO) cells (3,3, and 5 nM with the three cell lines, respectively). For dolastatin 10, IC50 values of 0.4 and 0.5 nM were obtained with the L1210 and CHO cells, respectively. At toxic concentrations dolastatin 15 caused the leukemia and lymphoma cells to arrest in mitosis. In the CHO cells both dolastatin 15 and dolastatin 10 caused moderate loss of microtubules at the IC50 values and complete disappearance of microtubules at concentrations 10-fold higher. Despite its potency and the loss of microtubules in treated cells, the interaction of dolastatin 15 with tubulin in vitro was weak. Its IC50 value for inhibition of glutamate-induced polymerization of tubulin was 23-mu-M, as compared to values of 1.2-mu-M for dolastatin 10 and 1.5-mu-M for vinblastine. Dolastatin 10 noncompetitively inhibits the binding of vincristine to tubulin, inhibits nucleotide exchange, stabilizes the colchicine binding activity of tubulin, and inhibits tubulin-dependent GTP hydrolysis (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990; Bai et al. J Biol Chem 265: 17141-17149, 1990). Only the latter reaction was inhibited by dolastatin 15. Nevertheless, its structural similarity to dolastatin 10 indicates that dolastatin 15 may bind weakly in the "vinca domain" of tubulin (a region of the protein we postulate to be physically close to but not identical with the specific binding site of vinca alkaloids and maytansinoids), presumably in the same site as dolastatin 10 (the "peptide site"). C1 NCI,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5025,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. FU NCI NIH HHS [CA-443440-1A1-02] NR 22 TC 108 Z9 116 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 23 PY 1992 VL 43 IS 12 BP 2637 EP 2645 DI 10.1016/0006-2952(92)90153-A PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JC915 UT WOS:A1992JC91500018 PM 1632820 ER PT J AU BABBITT, PC KENYON, GL MARTIN, BM CHAREST, H SLYVESTRE, M SCHOLTEN, JD CHANG, KH LIANG, PH DUNAWAYMARIANO, D AF BABBITT, PC KENYON, GL MARTIN, BM CHAREST, H SLYVESTRE, M SCHOLTEN, JD CHANG, KH LIANG, PH DUNAWAYMARIANO, D TI ANCESTRY OF THE 4-CHLOROBENZOATE DEHALOGENASE - ANALYSIS OF AMINO-ACID-SEQUENCE IDENTITIES AMONG FAMILIES OF ACYL-ADENYL LIGASES, ENOYL-COA HYDRATASES ISOMERASES, AND ACYL-COA THIOESTERASES SO BIOCHEMISTRY LA English DT Article ID DEHYDROGENASE BIFUNCTIONAL ENZYME; COMPLETE NUCLEOTIDE-SEQUENCE; PSEUDOMONAS-SPEC CBS-3; IRON UPTAKE SYSTEM; SP STRAIN CBS3; ESCHERICHIA-COLI; VIBRIO-ANGUILLARUM; MOLECULAR-CLONING; ASPERGILLUS-NIDULANS; GENE AB We have deduced the nucleotide sequence of the genes encoding the three components of 4-chlorobenzoate (4-CBA) dehalogenase from Pseudomonas sp. CBS-3 and examined the origin of these proteins by homology analysis. Open reading frame 1 (ORF1) encodes a 30-kDa 4-CBA-coenzyme A dehalogenase related to enoyl-coenzyme A hydratases functioning in fatty acid beta-oxidation. ORF2 encodes a 57-kDa protein which activates 4-CBA by acyl adenylation/thioesterification. This 4-CBA:coenzyme A ligase shares significant sequence similarity with a large group of proteins, many of which catalyze similar chemistry in beta-oxidation pathways or in siderophore and antibiotic synthetic pathways. These proteins have in common a short stretch of sequence, (T,S)(S,G)G(T,S)(T,E)G(L,X)PK(G,-), which is particularly highly conserved and which may represent an important new class of "signature" sequence. We were unable to find any proteins homologous in sequence to the 16-kDa 4-hydroxybenzoate-coenzyme A thioesterase encoded by ORF3. Analysis of the chemistry and function of the proteins found to be structurally related to the 4-CBA:coenzyme A ligase and the 4-CBA-coenzyme A dehalogenase supports the proposal that they evolved from a beta-oxidation pathway. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNITS,BETHESDA,MD 20892. UNIV QUEBEC,INRS SANTE,QUEBEC CITY H9R 1G6,QUEBEC,CANADA. UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. RP BABBITT, PC (reprint author), UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143, USA. RI Liang, Po-Huang /H-6610-2015; OI Sylvestre, Michel/0000-0002-6942-3373 FU NIAMS NIH HHS [AR17323]; NIGMS NIH HHS [GM40570, GM-28688] NR 75 TC 172 Z9 184 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 23 PY 1992 VL 31 IS 24 BP 5594 EP 5604 DI 10.1021/bi00139a024 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JA432 UT WOS:A1992JA43200024 PM 1351742 ER PT J AU BUENGER, GS MARQUEZ, VE AF BUENGER, GS MARQUEZ, VE TI CARBOCYCLIC RING-ENLARGED OXETANOCIN ANALOGS SO TETRAHEDRON LETTERS LA English DT Article AB Carbocyclic versions of 2'3'-dideoxy-3'C-hydroxymethyl nucleosides with adenine, guanine, uracil and cytosine bases were synthesized from a common cyclopentenone precursor. The extra hydroxymethyl moiety was introduced by photochemical addition of methanol to an alpha-enone system. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 12 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 23 PY 1992 VL 33 IS 26 BP 3707 EP 3710 DI 10.1016/S0040-4039(00)91993-2 PG 4 WC Chemistry, Organic SC Chemistry GA JA943 UT WOS:A1992JA94300001 ER PT J AU CRYSTAL, RG AF CRYSTAL, RG TI GENE-THERAPY STRATEGIES FOR PULMONARY-DISEASE SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT INVESTIGATORS MEETING ON ADVANCES IN OUTPATIENT ANTIMICROBIAL THERAPY : LORACARBEF CY JUN 12-15, 1991 CL SAN FRANCISCO, CA SP ELI LILLY ID ALPHA-1-ANTITRYPSIN DEFICIENCY; EMPHYSEMA; INVIVO; CELLS; DNA AB The two most common hereditary lung disorders in Caucasians, alpha-1-antitrypsin (alpha-1-AT) deficiency and cystic fibrosis, have their major clinical manifestations in the lung. Rapid advances in biotechnology have resulted in a variety of gene therapy strategies for the potential treatment of these disorders. Three vector systems-plasmid, retrovirus, and adenovirus-have been evaluated for their possible utility in transferring genes in a fashion that would either alter the milieu of the lung or directly alter the genetic program of lung parenchymal cells. Two general strategies can be used: ex vivo modification of autologous cells with subsequent transplantation to the patient and in vivo modification with an appropriate vector containing the exogenous gene. Studies carried out in experimental animals show that it is theoretically possible to treat both alpha-1-AT deficiency and cystic fibrosis with gene therapy if the safety hurdles can be overcome to minimize the risks involved. RP CRYSTAL, RG (reprint author), NHLBI,PULM BRANCH,6DO3 BLDG 10,BETHESDA,MD 20892, USA. NR 40 TC 29 Z9 30 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN 22 PY 1992 VL 92 SU 6A BP S44 EP S52 DI 10.1016/0002-9343(92)90607-D PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA JB170 UT WOS:A1992JB17000009 PM 1621744 ER PT J AU NOWAK, R AF NOWAK, R TI THE DUTCH WAY OF DEATH SO NEW SCIENTIST LA English DT Article RP NOWAK, R (reprint author), JOURNAL NIH RES,WASHINGTON,DC, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NEW SCIENTIST PUBL EXPEDITING INC PI ELMONT PA 200 MEACHAM AVE, ELMONT, NY 11003 SN 0262-4079 J9 NEW SCI JI New Sci. PD JUN 20 PY 1992 VL 134 IS 1826 BP 28 EP 30 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JA284 UT WOS:A1992JA28400035 PM 11656121 ER PT J AU CHANG, K PASTAN, I WILLINGHAM, MC AF CHANG, K PASTAN, I WILLINGHAM, MC TI FREQUENT EXPRESSION OF THE TUMOR-ANTIGEN CAK1 IN SQUAMOUS-CELL CARCINOMAS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MONOCLONAL-ANTIBODY; LUNG; DIAGNOSIS; CANCER AB K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples. C1 NCI,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NR 24 TC 51 Z9 51 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 19 PY 1992 VL 51 IS 4 BP 548 EP 554 DI 10.1002/ijc.2910510408 PG 7 WC Oncology SC Oncology GA JA553 UT WOS:A1992JA55300007 PM 1351045 ER PT J AU POWERS, R GARRETT, DS MARCH, CJ FRIEDEN, EA GRONENBORN, AM CLORE, GM AF POWERS, R GARRETT, DS MARCH, CJ FRIEDEN, EA GRONENBORN, AM CLORE, GM TI 3-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 BY MULTIDIMENSIONAL HETERONUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY SO SCIENCE LA English DT Article ID RESTRAINED MOLECULAR-DYNAMICS; CYTOKINE RECEPTOR SUPERFAMILY; CELL-STIMULATING FACTOR; 2D NMR-SPECTRA; DISTANCE GEOMETRY; FACTOR-I; COUPLING-CONSTANTS; HYDROGEN-EXCHANGE; PROTEINS; ASSIGNMENT AB The three-dimensional solution structure of recombinant human interleukin-4, a protein of 133 residues and 15.4 kilodaltons that plays a key role in the immune and inflammatory systems, has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is dominated by a left-handed four-helix bundle with an unusual topology comprising two overhand connections. The linker elements between the helices are formed by either long loops, small helical turns, or short strands. The overall topology is remarkably similar to that of growth hormone and granulocyte-macrophage colony stimulating factor, despite the absence of any sequence homology, and substantial differences in the relative lengths of the helices, the length and nature of the various connecting elements, and the pattern of disulfide bridges. These three proteins, however, bind to cell surface receptors belonging to the same hematopoietic superfamily, which suggests that interleukin-4 may interact with its receptor in an analogous manner to that observed in the crystal structure of the growth hormone-extracellular receptor complex. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. IMMUNEX CORP,SEATTLE,WA 98101. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 50 TC 145 Z9 147 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 19 PY 1992 VL 256 IS 5064 BP 1673 EP 1677 DI 10.1126/science.256.5064.1673 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HZ174 UT WOS:A1992HZ17400043 PM 1609277 ER PT J AU FULTZ, PN NARA, P BARRESINOUSSI, F CHAPUT, A GREENBERG, ML MUCHMORE, E KIENY, MP GIRARD, M AF FULTZ, PN NARA, P BARRESINOUSSI, F CHAPUT, A GREENBERG, ML MUCHMORE, E KIENY, MP GIRARD, M TI VACCINE PROTECTION OF CHIMPANZEES AGAINST CHALLENGE WITH HIV-1 INFECTED PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRUS; SECRETIONS; MACAQUES; ANTIBODY; TYPE-1; WOMEN; AIDS AB Because human immunodeficiency virus (HIV) can be transmitted as cell-free virus or as infected cells (cell-associated virus), vaccines must protect against infection by both viral forms. Vaccine-mediated protection of nonhuman primates against low doses of cell-free HIV-1, HIV-2, or simian immunodeficiency virus (SIV) has been demonstrated. It is now shown that multiple immunizations of chimpanzees with HIV-1 antigens protected against infection with cell-associated virus. Protection can persist for extended periods (one animal had not been exposed to viral antigens for 1 year before challenge). These results show that it is possible to elicit long-lasting protective immunity against cell-associated HIV-1. C1 NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. INST PASTEUR,F-75724 PARIS 15,FRANCE. NYU MED CTR,EXPTL MED & SURG PRIMATES LAB,NEW YORK,NY 10016. TRANSGENE SA,F-67082 STRASBOURG,FRANCE. DUKE UNIV,MED CTR,DURHAM,NC 27710. RP FULTZ, PN (reprint author), UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294, USA. RI Barre-Sinoussi, Francoise/G-8355-2011 NR 27 TC 150 Z9 150 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 JUN 19 PY 1992 VL 256 IS 5064 BP 1687 EP 1690 DI 10.1126/science.256.5064.1687 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HZ174 UT WOS:A1992HZ17400047 PM 1609280 ER PT J AU BIJUR, PE KURZON, M OVERPECK, MD SCHEIDT, PC AF BIJUR, PE KURZON, M OVERPECK, MD SCHEIDT, PC TI PARENTAL ALCOHOL-USE, PROBLEM DRINKING, AND CHILDRENS INJURIES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective. - Millions of US children are exposed to parents who are problem drinkers, yet there is little evidence about the effect of parental alcohol consumption on children's health. The aim of this study was to assess the association between children's injuries and parental drinking. Design. - Survey of a nationally representative sample of the US population by household interview. Participants. - 12360 children and parents from single-family households, with data from the Alcohol and Child Health supplements to the 1988 National Health Interview Survey. Main Outcome Measure. - Serious injuries-injuries resulting in hospitalization, surgical treatment, missed school, one half day or more in bed. Results. - Children of mothers categorized as problem drinkers had 2.1 times the risk of serious injury as children of mothers who were nondrinkers (95% CI, 1.3 to 3.5). Other measures of mothers' alcohol consumption (ie, average, maximum, and self-rated consumption) were unrelated to child injuries, as were all measures of fathers' drinking. Children of women who were problem drinkers married to men rated as moderate or heavy drinkers had a relative risk of serious injury of 2.7 (95% CI, 0.8 to 8.6) compared with children of nondrinkers. Conclusion. - Children of women who are problem drinkers have an elevated injury risk; children with two parents who are problem drinkers are at higher risk. Further research is needed on potential mechanisms and interventions. Primary prevention might be enhanced if physicians elicited information about parental drinking, helped secure appropriate treatment, and participated in public health efforts to reduce the deleterious effects of alcohol. C1 NICHHD,ROCKVILLE,MD. RP BIJUR, PE (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PEDIAT,ROOM 920,ROSE F KENNEDY CTR,BRONX,NY 10461, USA. FU NICHD NIH HHS [R01-HD25416-02] NR 28 TC 62 Z9 62 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 17 PY 1992 VL 267 IS 23 BP 3166 EP 3171 DI 10.1001/jama.267.23.3166 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA HX918 UT WOS:A1992HX91800025 PM 1593737 ER PT J AU LINEHAN, WM LONG, JP STEEG, PS GNARRA, JR AF LINEHAN, WM LONG, JP STEEG, PS GNARRA, JR TI METASTATIC MODELS AND MOLECULAR-GENETICS OF PROSTATE-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NCI,DIV CANC BIOL DIAGN & CTR,PATHOL LAB,BETHESDA,MD 20892. RP LINEHAN, WM (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,RM 2B47,BETHESDA,MD 20892, USA. NR 15 TC 7 Z9 8 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 17 PY 1992 VL 84 IS 12 BP 914 EP 915 DI 10.1093/jnci/84.12.914 PG 2 WC Oncology SC Oncology GA HY129 UT WOS:A1992HY12900001 PM 1629908 ER PT J AU SZNOL, M CLARK, JW SMITH, JW STEIS, RG URBA, WJ RUBINSTEIN, LV VANDERMOLEN, LA JANIK, J SHARFMAN, WH FENTON, RG CREEKMORE, SP KREMERS, P CONLON, K HURSEY, J BEVERIDGE, J LONGO, DL AF SZNOL, M CLARK, JW SMITH, JW STEIS, RG URBA, WJ RUBINSTEIN, LV VANDERMOLEN, LA JANIK, J SHARFMAN, WH FENTON, RG CREEKMORE, SP KREMERS, P CONLON, K HURSEY, J BEVERIDGE, J LONGO, DL TI PILOT-STUDY OF INTERLEUKIN-2 AND LYMPHOKINE-ACTIVATED KILLER-CELLS COMBINED WITH IMMUNOMODULATORY DOSES OF CHEMOTHERAPY AND SEQUENCED WITH INTERFERON-ALFA-2A IN PATIENTS WITH METASTATIC MELANOMA AND RENAL-CELL CARCINOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CONTINUOUS INFUSION INTERLEUKIN-2; RECOMBINANT HUMAN INTERLEUKIN-2; MALIGNANT-MELANOMA; PHASE-II; ANTITUMOR-ACTIVITY; ADVANCED CANCER; THERAPY; IMMUNOTHERAPY; INVIVO; CYCLOPHOSPHAMIDE AB Background: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclophosphamide or doxorubicin or by the biologic agent interferon-alpha. Purpose: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN alpha-2a) in patients with metastatic melanoma and renal cell carcinoma. Methods: IL-2 (3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN alpha-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. Results: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. Conclusions: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN alpha-2a as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen. C1 FREDERICK MEM HOSP,FREDERICK,MD. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP SZNOL, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74102] NR 47 TC 32 Z9 32 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 17 PY 1992 VL 84 IS 12 BP 929 EP 937 DI 10.1093/jnci/84.12.929 PG 9 WC Oncology SC Oncology GA HY129 UT WOS:A1992HY12900007 PM 1629914 ER PT J AU COATES, RJ BRANSFIELD, DD WESLEY, M HANKEY, B ELEY, JW GREENBERG, RS FLANDERS, D HUNTER, CP EDWARDS, BK FORMAN, M CHEN, VW REYNOLDS, P BOYD, P AUSTIN, D MUSS, H BLACKLOW, RS AF COATES, RJ BRANSFIELD, DD WESLEY, M HANKEY, B ELEY, JW GREENBERG, RS FLANDERS, D HUNTER, CP EDWARDS, BK FORMAN, M CHEN, VW REYNOLDS, P BOYD, P AUSTIN, D MUSS, H BLACKLOW, RS TI DIFFERENCES BETWEEN BLACK-AND-WHITE WOMEN WITH BREAST-CANCER IN TIME FROM SYMPTOM RECOGNITION TO MEDICAL CONSULTATION SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RACIAL-DIFFERENCES; SEEKING CARE; SURVIVAL; DELAY; STAGE; DIAGNOSIS; DISEASE; DETERMINANTS; INITIATION; RACE AB Background: Studies in the United States have reported that Black women have higher fatality rates than White women following a diagnosis of breast cancer and are more likely to be diagnosed with late-stage cancers. Purpose: To evaluate reasons for these racial differences, we explored the difference between Black and White women in the length of time from symptom recognition to initial medical consultation. We also evaluated the extent to which other factors related to the length of this interval might contribute to any observed racial difference. Methods: As part of a collaborative study of differences in the survival rates of Black patients and White patients with cancer, we interviewed a sample of 410 Black women and 325 White women from Atlanta, New Orleans, and San Francisco/Oakland who were newly diagnosed in 1985 or 1986 with invasive breast cancer. Retrospective data were collected on symptoms, dates of symptom recognition and initial medical consultation, and several other factors which may affect the interval between symptom recognition and medical consultation. Data were analyzed as if from a follow-up study, using product limit procedures and proportional hazards regression. Results: At diagnosis, Black women with breast cancer were two times more likely to have stage IV breast cancer and one and one-half times more likely to have stage III breast cancer than White women with breast cancer and were only approximately one-half as likely to have stage I breast cancer. Similarly, Black women were almost twice as likely as White women to have tumors that were larger than 5 cm or tumors that had extensions to the chest wall or skin at presentation. However, the average rate at which Black women with breast cancer obtained an initial medical consultation lagged behind that for White women by only a slight but statistically significant difference (15%). The median time between symptom recognition and medical consultation was slightly longer for Black women (16 days) than for White women (14 days) (P = .06). Adjustment for other characteristics predictive of the length of this interval had little effect on racial differences. The racial differences tended to vary somewhat by age and metropolitan area, suggesting that the results may not apply equally to all demographic subgroups and regions in the United States. Conclusion: This small difference in the time from symptom recognition to medical consultation is unlikely to account for the large racial differences in survival rates and in stage of disease at the time of diagnosis. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. CALIF DEPT HLTH,EMERYVILLE,CA. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,HEMATOL & ONCOL SECT,WINSTON SALEM,NC 27103. NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. VET ADM MED CTR,NASHVILLE,TN 37203. VANDERBILT UNIV,NASHVILLE,TN 37240. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,PHILADELPHIA,PA 19107. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. LOUISIANA STATE UNIV,MED CTR,SCH MED,DEPT PATHOL,NEW ORLEANS,LA 70112. RP COATES, RJ (reprint author), EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,1599 CLIFTON RD NE,ATLANTA,GA 30329, USA. FU NCI NIH HHS [N01CN-05227, N01CN-45174, N01CN-45175] NR 44 TC 98 Z9 99 U1 3 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 17 PY 1992 VL 84 IS 12 BP 938 EP 950 DI 10.1093/jnci/84.12.938 PG 13 WC Oncology SC Oncology GA HY129 UT WOS:A1992HY12900008 PM 1629915 ER PT J AU WILLIAMS, JC PEACOCK, MG WAAG, DM KENT, G ENGLAND, MJ NELSON, G STEPHENSON, EH AF WILLIAMS, JC PEACOCK, MG WAAG, DM KENT, G ENGLAND, MJ NELSON, G STEPHENSON, EH TI VACCINES AGAINST COXIELLOSIS AND Q-FEVER - DEVELOPMENT OF A CHLOROFORM-METHANOL RESIDUE SUBUNIT OF PHASE-I COXIELLA-BURNETII FOR THE IMMUNIZATION OF ANIMALS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SCN MICE; SHEEP; IMMUNITY; EXPOSURE; VACCINATION; CHALLENGE; PNEUMONIA; EWES C1 USA,MED RES INST INFECT DIS,DEPT INTRACELLULAR PATHOGENS,DIV BACTERIOL,FREDERICK,MD 21701. USA,MED RES INST INFECT DIS,DIV BIOMETR & INFORMAT MANAGEMENT,FREDERICK,MD 21701. NIAID,OFF SCI DIRECTOR,BETHESDA,MD 20892. ROCKY MT LABS,HAMILTON,MT 59840. UNIV MARYLAND,VIRGINIA MARYLAND REG COLL VET COLL,COLL PK,MD 20742. USA,MED RES INST INFECT DIS,FREDERICK,MD 21701. HOSP SICK CHILDREN,TORONTO M5G 1X8,ONTARIO,CANADA. NR 40 TC 15 Z9 15 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 16 PY 1992 VL 653 BP 88 EP 111 DI 10.1111/j.1749-6632.1992.tb19633.x PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM564 UT WOS:A1992JM56400012 PM 1626897 ER PT J AU HAYUNGA, EG SUMNER, MP DUNCAN, JF CHAKRABARTI, EK WEBERT, DW AF HAYUNGA, EG SUMNER, MP DUNCAN, JF CHAKRABARTI, EK WEBERT, DW TI PRODUCTION OF ANTIIDIOTYPIC ANTIBODIES AS POTENTIAL IMMUNOREAGENTS FOR THE SEROLOGICAL DIAGNOSIS OF BOVINE CYSTICERCOSIS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID HYDROPHOBIC CHROMATOGRAPHY; MONOCLONAL-ANTIBODIES; CYST FLUID; TAENIA C1 KIRKEGAARD & PERRY LABS INC,GAITHERSBURG,MD 20879. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,DIV TROP PUBL HLTH,BETHESDA,MD 20814. USDA,FOOD SAFETY & INSPECT SERV,DIV PATHOL & SEROL,BELTSVILLE,MD 20705. RP HAYUNGA, EG (reprint author), NIH,DIV RES GRANTS,BETHESDA,MD 20892, USA. NR 13 TC 12 Z9 13 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 16 PY 1992 VL 653 BP 178 EP 183 DI 10.1111/j.1749-6632.1992.tb19642.x PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM564 UT WOS:A1992JM56400021 PM 1626868 ER PT J AU WILLIAMS, JC KOCAN, KM AHL, AS KAKOMA, I GIBBS, EPJ AF WILLIAMS, JC KOCAN, KM AHL, AS KAKOMA, I GIBBS, EPJ TI 1ST BIENNIAL CONFERENCE OF THE AMERICAN-SOCIETY-OF TROPICAL-VETERINARY-MEDICINE WHICH WAS HELD BY THE AMERICAN-SOCIETY-OF-TROPICAL-VETERINARY-MEDICINE ON FEBRUARY 5-8, 1991 IN SAN-JUAN, PUERTO-RICO - PREFACE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material C1 USA,MED RES INST INFECT DIS,DEPT INTRACELLULAR PATHOGENS,DIV BACTERIOL,FREDERICK,MD 21701. NIAID,OFF SCI DIRECTOR,BETHESDA,MD 20892. OKLAHOMA STATE UNIV,COLL VET MED,DEPT VET PATHOL,STILLWATER,OK 74078. USDA,ANIM & PLANT HLTH INSPECT SERV,RISK ANAL SECT,HYATTSVILLE,MD 20782. UNIV FLORIDA,COLL VET MED,GAINESVILLE,FL 32610. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 16 PY 1992 VL 653 BP R11 EP R12 DI 10.1111/j.1749-6632.1992.tb19622.x PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM564 UT WOS:A1992JM56400001 ER PT J AU NICHOLSON, LK KAY, LE BALDISSERI, DM ARANGO, J YOUNG, PE BAX, A TORCHIA, DA AF NICHOLSON, LK KAY, LE BALDISSERI, DM ARANGO, J YOUNG, PE BAX, A TORCHIA, DA TI DYNAMICS OF METHYL-GROUPS IN PROTEINS AS STUDIED BY PROTON-DETECTED C-13 NMR-SPECTROSCOPY - APPLICATION TO THE LEUCINE RESIDUES OF STAPHYLOCOCCAL NUCLEASE SO BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE RELAXATION; MODEL-FREE APPROACH; DIFFRACTION STRUCTURE DETERMINATION; SPERM WHALE MYOGLOBIN; POLARIZATION TRANSFER; MOLECULAR-STRUCTURE; BACKBONE DYNAMICS; ACID COMPONENTS; SPIN RELAXATION; H-1 AB This paper describes the application of recently developed nuclear magnetic resonance (NMR) pulse sequences to obtain information about the internal dynamics of isotopically enriched hydrophobic side chains in proteins. The two-dimensional spectra provided by the pulse sequences enable one to make accurate measurements of nuclear Overhauser effects (NOE) and longitudinal (T1) and transverse (T2) relaxation times of enriched methyl carbons in proteins. Herein, these techniques are used to investigate the internal dynamics of the 11 leucine side chains of staphylococcal nuclease (SNase), a small enzyme having M(r) = 16.8K, in the absence and presence of ligands thymidine 3',5'-bisphosphate (pdTp) and Ca2+. We report the synthesis of [5,5'-C-13(2)]leucine, the preparation of SNase containing the labeled leucine, the sequential assignment of the leucine methyl carbons and protons in the liganded and unliganded proteins, and the measurement of the C-13 T1, T2, and NOE values for the SNase leucine methyl carbons. Analysis of the relaxation parameters using the formalism of Lipari and Szabo shows that the internal motions of the leucine methyl carbons are characterized by effective correlation times tau(f) (5-80 ps) and tau(s) (<2 ns). The fast motion is identified with the rapid rotation of the methyl group about the C(gamma)-C(delta) bond axis, while the slow motion is associated with reorientation of the C(gamma)-C(delta) bond axis itself. The mean squared order parameters associated with the latter motion, S(s)2, lie in the range 0.34-0.92. The values of S(s)2 correlate reasonably well with the temperature factors of the leucine methyl carbons obtained from the crystal structures, but some are smaller than anticipated on the basis of the fact that nearly all leucine methyl carbons are buried and have temperature factors no larger than that of the leucine backbone atoms. Five leucine residues in liganded SNase and eight in unliganded SNase have values of S(s)2 less than 0.71. These order parameters correspond to large amplitude motions (angular excursions of 27-67-degrees) of the C(gamma)-C(delta) bond axis. These results indicate that, in solution, the internal motions of the leucine side chains of SNase are significantly larger than suggested by the X-ray structures or by qualitative analysis of NOESY spectra. Comparison of S(s)2 values obtained from liganded and unliganded SNase reveals a strong correlation between DELTA-S(s)2 and distance between the leucine methyl carbon and the ligands. A significant increase in S(s)2 upon ligand binding occurs exclusively in those leucine side chains in the vicinity (<10 angstrom) of either the Ca2+ atom or the pdTp heavy atoms, indicating a localized stiffening of the protein structure in regions near the ligand-binding sites. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. CUNY YORK COLL,DEPT CHEM,JAMAICA,NY 11451. FU NCRR NIH HHS [RR08153] NR 57 TC 243 Z9 245 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 16 PY 1992 VL 31 IS 23 BP 5253 EP 5263 DI 10.1021/bi00138a003 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ176 UT WOS:A1992HZ17600003 PM 1606149 ER PT J AU BARBATO, G IKURA, M KAY, LE PASTOR, RW BAX, A AF BARBATO, G IKURA, M KAY, LE PASTOR, RW BAX, A TI BACKBONE DYNAMICS OF CALMODULIN STUDIED BY N-15 RELAXATION USING INVERSE DETECTED 2-DIMENSIONAL NMR-SPECTROSCOPY - THE CENTRAL HELIX IS FLEXIBLE SO BIOCHEMISTRY LA English DT Article ID MODEL-FREE APPROACH; STOCHASTIC SIMULATIONS; TROPONIN-C; 3D NMR; PROTEINS; C-13; MACROMOLECULES; ASSIGNMENT; CRYSTAL; BINDING AB The backbone dynamics of Ca2+-saturated recombinant Drosophila calmodulin has been studied by N-15 longitudinal and transverse relaxation experiments, combined with N-15{H-1} NOE measurements. Results indicate a high degree of mobility near the middle of the central helix of calmodulin, from residue K77 through S81, with order parameters (S2) in the 0.5-0.6 range. The anisotropy observed in the motion of the two globular calmodulin domains is much smaller than expected on the basis of hydrodynamic calculations for a rigid dumbbell type structure. This indicates that, for the purposes of N-15 relaxation, the tumbling of the N-terminal (L4-K77) and C-terminal (E82-S147) lobes of calmodulin is effectively independent. A slightly shorter motional correlation time (tau(c) almost-equal-to 6.3 ns) is obtained for the C-terminal domain compared to the N-terminal domain (tau(c) almost-equal-to 7.1 ns), in agreement with the smaller size of the C-terminal domain. A high degree of mobility, with order parameters of approximately 0.5, is also observed in the loop that connects the first with the second EF-hand type calcium binding domain and in the loop connecting the third and fourth calcium binding domain. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. RI Barbato, Gaetano/G-4904-2011 NR 42 TC 794 Z9 798 U1 6 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 16 PY 1992 VL 31 IS 23 BP 5269 EP 5278 DI 10.1021/bi00138a005 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ176 UT WOS:A1992HZ17600005 PM 1606151 ER PT J AU KONSTAM, MA KRONENBERG, MW UDELSON, JE KINAN, D METHERALL, J DOLAN, N EDENS, T HOWE, D KILCOYNE, L BENEDICT, C YOUNGBLOOD, M BARRETT, J YUSUF, S AF KONSTAM, MA KRONENBERG, MW UDELSON, JE KINAN, D METHERALL, J DOLAN, N EDENS, T HOWE, D KILCOYNE, L BENEDICT, C YOUNGBLOOD, M BARRETT, J YUSUF, S TI EFFECTIVENESS OF PRELOAD RESERVE AS A DETERMINANT OF CLINICAL STATUS IN PATIENTS WITH LEFT-VENTRICULAR SYSTOLIC DYSFUNCTION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; IDIOPATHIC DILATED CARDIOMYOPATHY; PRESSURE-VOLUME RELATIONS; MYOCARDIAL-INFARCTION; EXERCISE; HEMODYNAMICS; RELAXATION; UPRIGHT; DISEASE; RATS AB The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve - LV distension during exercise - was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less-than-or-equal-to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p <0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p <0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p <0.000.5]), contributing to a greater increase in LV minute output (p <0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p <0.0005) and LV output response increased slightly (p <0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response. In patients with symptomatic heart failure, preload reserve is absent, and the cardiac output response depends solely on heart rate. Enalapril may augment preload reserve. C1 TUFTS UNIV,NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA 02111. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT RADIOL,NASHVILLE,TN 37232. UNIV TEXAS,HLTH SCI CTR,DEPT MED,HOUSTON,TX 77225. UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINATING,DEPT BIOSTAT,CHAPEL HILL,NC 27514. NHLBI,CLIN TRIAL BRANCH,BETHESDA,MD 20892. RP KONSTAM, MA (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR,DEPT MED,BOX 108,750 WASHINGTON ST,BOSTON,MA 02111, USA. FU NHLBI NIH HHS [N01-HC55010] NR 30 TC 29 Z9 29 U1 1 U2 1 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 JUN 15 PY 1992 VL 69 IS 19 BP 1591 EP 1595 DI 10.1016/0002-9149(92)90709-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HY864 UT WOS:A1992HY86400015 PM 1598875 ER PT J AU DIODATI, JG SCHENKE, WH WACLAWIW, MA MCINTOSH, CL CANNON, RO AF DIODATI, JG SCHENKE, WH WACLAWIW, MA MCINTOSH, CL CANNON, RO TI PREDICTORS OF EXERCISE BENEFIT AFTER OPERATIVE RELIEF OF LEFT-VENTRICULAR OUTFLOW OBSTRUCTION BY THE MYOTOMY-MYECTOMY PROCEDURE IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TERM FOLLOW-UP; SUBAORTIC STENOSIS; CLINICAL MANIFESTATIONS; SYMPTOMATIC STATUS; PATHO-PHYSIOLOGY; SEPTAL MYOTOMY; INTERRELATIONS; DETERMINANTS; PERFORMANCE; THERAPY AB To determine predictors of exercise benefit in patients with hypertrophic cardiomyopathy after operative relief of left ventricular (LV) outflow tract obstruction, 30 patients underwent catheterization and exercise testing before and 6 months after operation, and hemodynamic measurements were obtained. The increase in maximal oxygen consumption (VO2max) during treadmill exercise testing was chosen as an index of exercise benefit. Univariate analysis showed a significant positive correlation of operative change in VO2max with preoperative LV end-diastolic and pulmonary arterial wedge pressures, operative change in exercise duration, and operative reductions in LV end-diastolic and pulmonary arterial wedge pressures and resting LV outflow tract gradient, and a significant negative correlation with preoperative VO2max and percent predicted VO2max. Multivariate analysis by stepwise linear regression of only significant univariate variables selected only preoperative percent predicted VO2max, and operative reduction in LV end-diastolic pressure and resting LV outflow tract gradient as significant predictors of postoperative change in VO2max. Stepwise regression analysis, applied only to preoperative exercise and catheterization hemodynamic variables, selected only preoperative percent predicted VO2max and preoperative LV end-diastolic pressure as predictors of improvement in exercise capacity. Thus, patients with obstructive hypertrophic cardiomyopathy, after failing medical therapy, are most likely to demonstrate improvement in exercise capacity if preoperative exercise testing demonstrates limited exercise capacity and if surgery achieves reduction in elevated resting LV outflow tract gradients and LV filling pressures. RP DIODATI, JG (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B15,BETHESDA,MD 20892, USA. NR 18 TC 13 Z9 13 U1 0 U2 1 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 JUN 15 PY 1992 VL 69 IS 19 BP 1617 EP 1622 DI 10.1016/0002-9149(92)90713-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HY864 UT WOS:A1992HY86400019 PM 1598879 ER PT J AU DOSEMECI, M WACHOLDER, S LUBIN, JH AF DOSEMECI, M WACHOLDER, S LUBIN, JH TI DOES NONDIFFERENTIAL MISCLASSIFICATION OF EXPOSURE ALWAYS BIAS A TRUE EFFECT TOWARD THE NULL VALUE - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP DOSEMECI, M (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BLDG EPN,ROOM 418,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 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 JUN 15 PY 1992 VL 135 IS 12 BP 1430 EP 1431 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KT259 UT WOS:A1992KT25900018 ER PT J AU DESMET, MD RUBIN, BI WHITCUP, SM LOPEZ, JS AUSTIN, HA NUSSENBLATT, RB AF DESMET, MD RUBIN, BI WHITCUP, SM LOPEZ, JS AUSTIN, HA NUSSENBLATT, RB TI COMBINED USE OF CYCLOSPORINE AND KETOCONAZOLE IN THE TREATMENT OF ENDOGENOUS UVEITIS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID BEHCETS-DISEASE; THERAPY AB Ten patients with endogenous uveitis were in clinical remission attributable to treatment with cyclosporine and prednisone. After the cyclosporine dose was reduced by two thirds, these patients were randomly assigned to treatment with or without ketoconazole, a potent inhibitor of cytochrome P-450, in a double-masked placebo-controlled study. The dose was reduced over three days. During a three-month follow-up, no patients treated with ketoconazole had a relapse of uveitis, while four of six (66%) control subjects had a flare-up. Toxicity in the ketoconazole-treated group was limited to a transient decrease in glomerular filtration rate (20% from baseline) at one month in two of six (33%) patients. Renal function was stabilized by further reduction of the cyclosporine dose. C1 NIADDKD,BETHESDA,MD 20892. RP DESMET, MD (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N202,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 11 TC 11 Z9 12 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN 15 PY 1992 VL 113 IS 6 BP 687 EP 690 PG 4 WC Ophthalmology SC Ophthalmology GA HX952 UT WOS:A1992HX95200012 PM 1598960 ER PT J AU TORRENCE, PF BROZDA, D ALSTER, DK PABUCCUOGLU, A LESIAK, K AF TORRENCE, PF BROZDA, D ALSTER, DK PABUCCUOGLU, A LESIAK, K TI A NEW AND POTENT 2-5A ANALOG WHICH DOES NOT REQUIRE A 5'-POLYPHOSPHATE TO ACTIVATE MOUSE L-CELL RNASE-L SO ANTIVIRAL RESEARCH LA English DT Article DE INTERFERON; ANTIVIRAL AGENT; PROTEIN SYNTHESIS INHIBITION ID DOUBLE-STRANDED-RNA; BIOLOGICAL-ACTIVITIES; 2-5A-DEPENDENT RNASE; CHEMICAL SYNTHESIS; INTERFERON; INHIBITION; BINDING; 2',5'-OLIGOADENYLATES; PHOSPHORYLATION; SYNTHETASE AB In order to explore the possibility of supplanting the requirement of a 5'-triphosphate moiety for the activation of the 2-5A-dependent endonuclease (RNase L) of mouse L-cells, two new tetrameric analogues of 2-5A were synthesized. The first tetramer, obtained by both a modified prebiotic synthetic approach as well as a phosphite triester solid phase oligonucleotide synthesis method, was p5'A2'p5'A2'p5'(br8A)2'p5'(br8A). The second oligonucleotide was derived from the former by a sequence involving periodate oxidation, reaction with n-hexylamine, and cyanoborohydride reduction, resulting in conversion of the 2'-terminal adenosine residue to 9-(3'-aza-4'-hexyl-1',2',3',4'-tetradeoxyhexopyranos-l(1)-yl)-8-bromoadenine. Both of these oligomers, bearing only 5'-monophosphate groups, were found to be as potent as 2-5A itself as activators of the RNase L of mouse L-cells. RP TORRENCE, PF (reprint author), NIDDKD,MED CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892, USA. NR 27 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN 15 PY 1992 VL 18 IS 3-4 BP 275 EP 289 DI 10.1016/0166-3542(92)90061-9 PG 15 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA JA499 UT WOS:A1992JA49900004 PM 1416909 ER PT J AU WATANABE, T JIMENEZMOLINA, JL CHOU, JY AF WATANABE, T JIMENEZMOLINA, JL CHOU, JY TI CHARACTERIZATION OF A RAT VARIANT ALPHA-FETOPROTEIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LIVER DIFFERENTIATION INVITRO; MESSENGER-RNA; SEQUENCE ORGANIZATION; GENE-EXPRESSION; ALBUMIN GENES; FETAL; ALPHA-1-FETOPROTEIN; REGION; TRANSCRIPTION; HYBRIDIZATION C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 34 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1992 VL 185 IS 2 BP 648 EP 656 DI 10.1016/0006-291X(92)91674-F PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HZ252 UT WOS:A1992HZ25200024 PM 1376990 ER PT J AU PARK, KS SOHN, DH VEECH, RL SONG, BJ AF PARK, KS SOHN, DH VEECH, RL SONG, BJ TI PRETRANSLATIONAL INDUCTION OF PENTOXYRESORUFIN O-DEPENTYLASE BY PYRIDINE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT-LIVER; CYTOCHROME-P-450; HYBRIDIZATION; ACETONE RP PARK, KS (reprint author), NIAAA,METAB & MOLEC BIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1992 VL 185 IS 2 BP 676 EP 682 DI 10.1016/0006-291X(92)91678-J PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HZ252 UT WOS:A1992HZ25200028 PM 1610360 ER PT J AU MAUVIEL, A EVANS, CH UITTO, J AF MAUVIEL, A EVANS, CH UITTO, J TI LEUKOREGULIN DOWN-REGULATES TYPE-I COLLAGEN MESSENGER-RNA LEVELS AND PROMOTER ACTIVITY IN HUMAN DERMAL FIBROBLASTS, AND COUNTERACTS THE UP-REGULATION ELICITED BY TRANSFORMING GROWTH-FACTOR-BETA SO BIOCHEMICAL JOURNAL LA English DT Article ID HUMAN-SKIN FIBROBLASTS; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; RECOMBINANT INTERLEUKIN-1; INTERFERON-GAMMA; CELLS; FACTOR-BETA-1; MODULATION; ACTIVATION; MECHANISMS AB Leukoregulin (LR), a T-cell-derived growth factor, modulates fibroblast functions in vitro [Mauviel, Redini, Hartmann, Loyau & Pujol (1991) J. Cell Biol. 113, 1455-14621. In the present study, incubation of human dermal fibroblasts with LR (0.1-2 units/ml) resulted in decreases in the mRNA steady-state levels for alpha-1(I), alpha-2(I) and alpha-1(III), but not alpha-2(V), collagen genes. LR also down-regulated alpha-2(I) collagen promoter activity in transient cell transfections of control cells as well as those incubated with transforming growth factor-beta, a potent up-regulator of collagen type I gene expression. Thus LR is a strong inhibitor of type I collagen gene expression, acting at the level of transcription. C1 THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT DERMATOL, PHILADELPHIA, PA 19107 USA. THOMAS JEFFERSON UNIV, JEFFERSON INST MOLEC MED, MOLEC DERMATOL SECT, PHILADELPHIA, PA 19107 USA. THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT BIOCHEM & MOLEC BIOL, PHILADELPHIA, PA 19107 USA. NCI, DIV CANC ETIOL, TUMOR BIOL SECT, BIOL LAB, BETHESDA, MD 20892 USA. RI MAUVIEL, Alain/F-6251-2013 FU NIAMS NIH HHS [T32-AR0751, AR-41439] NR 40 TC 10 Z9 10 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1992 VL 284 BP 629 EP 632 PN 3 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JA275 UT WOS:A1992JA27500004 PM 1622385 ER PT J AU GUTIERREZ, MI BHATIA, K BARRIGA, F DIEZ, B MURIEL, FS DEANDREAS, ML EPELMAN, S RISUENO, C MAGRATH, IT AF GUTIERREZ, MI BHATIA, K BARRIGA, F DIEZ, B MURIEL, FS DEANDREAS, ML EPELMAN, S RISUENO, C MAGRATH, IT TI MOLECULAR EPIDEMIOLOGY OF BURKITT-LYMPHOMA FROM SOUTH-AMERICA - DIFFERENCES IN BREAKPOINT LOCATION AND EPSTEIN-BARR-VIRUS ASSOCIATION FROM TUMORS IN OTHER WORLD REGIONS SO BLOOD LA English DT Article ID C-MYC ONCOGENE; EXPRESSION C1 NCI,CLIN ONCOL PROGRAM,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. CATHOLIC UNIV CHILE,CTR INVEST MED,SANTIAGO,CHILE. HOSP NINOS DR RICARDO GUTIERREZ,BUENOS AIRES,ARGENTINA. HOSP NACL PEDIAT,BUENOS AIRES,ARGENTINA. HOSP AC CARMARGO FUNDACAO ANTONIO PRUDENTE,SAO PAULO,BRAZIL. NR 16 TC 88 Z9 89 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1992 VL 79 IS 12 BP 3261 EP 3266 PG 6 WC Hematology SC Hematology GA HY946 UT WOS:A1992HY94600020 PM 1317726 ER PT J AU LYNCH, JW LINOILLA, I SAUSVILLE, EA STEINBERG, SM GHOSH, BC NGUYEN, DT SCHECHTER, GP FISCHMANN, AB IHDE, DC STOCKER, JL BASTIAN, A TURNER, R COTELINGAM, JD GAZDAR, AF FOSS, FM AF LYNCH, JW LINOILLA, I SAUSVILLE, EA STEINBERG, SM GHOSH, BC NGUYEN, DT SCHECHTER, GP FISCHMANN, AB IHDE, DC STOCKER, JL BASTIAN, A TURNER, R COTELINGAM, JD GAZDAR, AF FOSS, FM TI PROGNOSTIC IMPLICATIONS OF EVALUATION FOR LYMPH-NODE INVOLVEMENT BY T-CELL ANTIGEN RECEPTOR GENE REARRANGEMENT IN MYCOSIS-FUNGOIDES SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SEZARY SYNDROME; MARKERS; CHAIN C1 USN HOSP,NCI,MED ONCOL BRANCH,BLDG 8,RM 5101,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. VET AFFAIRS MED CTR,WASHINGTON,DC. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NR 22 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1992 VL 79 IS 12 BP 3293 EP 3299 PG 7 WC Hematology SC Hematology GA HY946 UT WOS:A1992HY94600024 PM 1596570 ER PT J AU BRODER, S AF BRODER, S TI THE BETHESDA SYSTEM FOR REPORTING CERVICAL VAGINAL CYTOLOGIC DIAGNOSIS - REPORT OF THE 1991 BETHESDA WORKSHOP SO CANCER LA English DT Editorial Material RP BRODER, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1992 VL 69 IS 12 BP 3020 EP 3020 DI 10.1002/1097-0142(19920615)69:12<3020::AID-CNCR2820691228>3.0.CO;2-I PG 1 WC Oncology SC Oncology GA HX306 UT WOS:A1992HX30600031 ER PT J AU BELL, RH KUHLMANN, ET JENSEN, RT LONGNECKER, DS AF BELL, RH KUHLMANN, ET JENSEN, RT LONGNECKER, DS TI OVEREXPRESSION OF CHOLECYSTOKININ RECEPTORS IN AZASERINE-INDUCED NEOPLASMS OF THE RAT PANCREAS SO CANCER RESEARCH LA English DT Article ID EXOGENOUS CHOLECYSTOKININ; NUDE-MICE; GROWTH; CANCER; ANTAGONIST; SECRETIN; CERULEIN; STIMULATION; BOMBESIN; FLOUR AB Cholecystokinin (CCK) is a growth factor for normal pancreas. Numerous studies also suggest that CCK promotes pancreatic carcinogenesis in the rat. Our previous studies suggested that growth of preneoplastic pancreatic foci was stimulated by CCK more than that of normal pancreas. We hypothesized that such differential growth might be due to increased numbers of CCK receptors in neoplastic tissue. Azaserine-induced pancreatic carcinoma (DSL6) had an increased high-affinity CCK receptor binding capacity of 122 +/- 23 (SD) fmol/mg protein compared to 12 +/- 2 fmol/mg protein in normal pancreas (P < 0.001). The K(d) of the high-affinity site was 0.33 +/- 0.04 nm for carcinoma and 0.46 +/- 0.08 nm for normal pancreas (P < 0.01). The amount of cholecystokinin octapeptide (CCK-8) bound to high-affinity receptor was 8.6 +/- 1.9 fmol/mg protein for DSL6 compared to 0.6 +/- 0.2 fmol/mg protein in normal pancreas (P < 0.001). Azaserine-induced premalignant nodules were compared to remaining internodular pancreas. Nodules demonstrated a mean high-affinity CCK receptor binding capacity of 38 +/- 9 fmol/mg protein compared to 6 +/- 3 fmol/mg protein in internodular pancreas (P < 0.001). The amount of CCK-8 bound to high-affinity receptor was 3.1 +/- 0.8 fmol/mg protein in nodules compared to 0.6 +/- 0.3 fmol/mg protein in internodular pancreas (P < 0.001). Overexpression of high-affinity CCK-8 receptor in premalignant and malignant azaserine-induced tumors may result in a growth advantage relative to normal pancreas. C1 DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT PATHOL,BOX 7600,HANOVER,NH 03756. NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA 23108, CA 47327]; NIEHS NIH HHS [ES-03687] NR 28 TC 44 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3295 EP 3299 PG 5 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400007 PM 1596887 ER PT J AU KROEGERKOEPKE, MB KOEPKE, SR HERNANDEZ, L MICHEJDA, CJ AF KROEGERKOEPKE, MB KOEPKE, SR HERNANDEZ, L MICHEJDA, CJ TI ACTIVATION OF A BETA-HYDROXYALKYLNITROSAMINE TO ALKYLATING-AGENTS - EVIDENCE FOR THE INVOLVEMENT OF A SULFOTRANSFERASE SO CANCER RESEARCH LA English DT Article ID SULFURIC-ACID ESTERS; HYDROXYLATED NITROSAMINES; CARCINOGENIC METABOLITE; N-NITROSODIETHANOLAMINE; SALMONELLA-TYPHIMURIUM; BRACHYMORPHIC MICE; RAT; LIVER; DNA; NITROSODIMETHYLAMINE AB N-Nitrosomethyl(2-hydroxyethyl)amine (NMHEA), when administered by gavage, is a strong liver carcinogen in F344 female rats, but a weak liver carcinogen in male rats. After repeated exposure to NMHEA, either in drinking water or by gavage, female rats accumulated higher levels of DNA-guanine adducts than did their male counterparts, suggesting a correlation with the observed disparity in carcinogenicity. NMHEA has been shown to alkylate rat liver DNA in vivo in a dose-dependent manner. Chemical investigations of NMHEA suggest that it becomes a strong electrophile when a good leaving group is substituted on the hydroxyl. We have proposed that NMHEA is activated to its ultimate carcinogenic form by conjugation with sulfate. The sulfate ester was postulated to undergo rapid cyclization to 3-methyl-1,2,3-oxadiazolinium ion, which has previously been found to be a potent methylating agent in vitro. The effect of sulfotransferase inhibitors on the DNA alkylation in rats by NMHEA was studied in vivo. Dichloronitrophenol, a powerful inhibitor of phenol sulfotransferase, had little effect on the methylation and O6-hydroxyethylation of DNA guanine in female rats, while depressing the hydroxyethylation of the N-7 position of guanine. Dichloronitrophenol, however, dramatically enhanced the methylation of DNA in male rats. It also slightly inhibited the N-nitrosodimethylamine-induced methylation of DNA. On the other hand, propylene glycol, an alcohol sulfotransferase inhibitor, had a profound inhibitory effect on DNA methylation induced by NMHEA, very little effect on the formation of N7-(2-hydroxyethyl)guanine, but a very strong effect on the O6-hydroxyethylguanine lesions. NMHEA-induced alkylation was also studied in male and female brachymorphic mice, which are deficient in the ability to synthesize the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate required for sulfotransferase activity, and their heterozygous siblings. No significant differences were seen between the heterozygous and brachymorphic mice in overall levels of alkylation, except in the case of 7-hydroxyethylation. In contrast to rats, male mice showed higher levels of formation of all DNA guanine adducts than did the females. However, propylene glycol was found to depress all the levels of alkylation in the brachymorphic mice, except for N-(2-hydroxyethyl)guanine, as was observed in rats. Additional DNA alkylation experiments in vitro showed that methylation occurred in a dose-dependent manner with added inorganic sulfate when NMHEA was activated by either freshly isolated primary hepatocytes or intact cultured hepatocytes. Methylation of calf thymus DNA by [methyl-C-14]NMHEA was independently demonstrated by the production of [C-14]7-methylguanine in the presence of 3'-phosphoadenosine 5'-phosphosulfate and rat liver cytosol. These data support the hypothesis that methylation of DNA, at least in part, is due to an intermediate formed by the interaction of NMHEA with sulfate. The sulfotransferase enzyme responsible for NMHEA conjugation is not inhibited by dichloronitrophenol but is strongly inhibited by propylene glycol. 7-Hydroxyethylation of DNA must occur by a mechanism different from that of methylation or O6-hydroxyethylation. RP KROEGERKOEPKE, MB (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702, USA. FU PHS HHS [N01-74101] NR 30 TC 26 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3300 EP 3305 PG 6 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400008 PM 1596888 ER PT J AU CARTER, HB MORRELL, CH PEARSON, JD BRANT, LJ PLATO, CC METTER, EJ CHAN, DW FOZARD, JL WALSH, PC AF CARTER, HB MORRELL, CH PEARSON, JD BRANT, LJ PLATO, CC METTER, EJ CHAN, DW FOZARD, JL WALSH, PC TI ESTIMATION OF PROSTATIC GROWTH USING SERIAL PROSTATE-SPECIFIC ANTIGEN MEASUREMENTS IN MEN WITH AND WITHOUT PROSTATE DISEASE SO CANCER RESEARCH LA English DT Article ID MIXED-EFFECTS MODELS; HYPERPLASIA; ADENOCARCINOMA; CANCER; AGE AB Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT LAB MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP CARTER, HB (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205, USA. RI Fozard, James Leonard/B-3660-2009 NR 18 TC 177 Z9 181 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 JUN 15 PY 1992 VL 52 IS 12 BP 3323 EP 3328 PG 6 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400012 PM 1375867 ER PT J AU KAUR, G VIALLET, J LABORDA, J BLAIR, O GAZDAR, AF MINNA, JD SAUSVILLE, EA AF KAUR, G VIALLET, J LABORDA, J BLAIR, O GAZDAR, AF MINNA, JD SAUSVILLE, EA TI GROWTH-INHIBITION BY CHOLERA-TOXIN OF HUMAN LUNG-CARCINOMA CELL-LINES - CORRELATION WITH GM1 GANGLIOSIDE EXPRESSION SO CANCER RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; L-DOPA DECARBOXYLASE; BACTERIAL TOXINS; CANCER; DIFFERENTIATION; CHROMOGRANIN; ACTIVATION; ENDOCRINE; CALCIUM; MARKERS AB The effect of cholera toxin (CT) on the growth of 12 small cell lung carcinoma (SCLC) and 15 non-small cell lung carcinoma (NSCLC) cell lines is presented. CT inhibited the growth of nine SCLC cell lines (concentration for 50% inhibition of growth, 27-700 ng/ml), all of which had abundant expression of G(M1) ganglioside, the surface receptor for CT. CT-resistant SCLC all had greatly decreased G(M1) expression. In contrast, CT inhibited the growth of only four of 15 NSCLC cell lines. Seven of the 11 CT-resistant NSCLC had levels of G(M1) comparable to CT-sensitive NSCLC or SCLC. In a limited panel of cell lines, cyclic AMP (cAMP) agonists including forskolin, 8Br[cAMP], and dibutyryl[cAMP] did not consistently reproduce CT-mediated inhibition of cell growth, nor did these compounds overcome resistance of cells to the growth inhibitory effects of CT. Expression of the R(I) and R(II) regulatory subunits of cAMP-dependent protein kinase was similar in CT-resistant and CT-sensitive SCLC or NSCLC cell lines. In the presence of isobutylmethylxanthine, intracellular cAMP levels induced by CT in a CT-resistant, G(M1)(+) NSCLC cell line were comparable to those achieved in a CT-sensitive NSCLC cell line. We conclude that inhibition of lung carcinoma cell growth by CT in all cases requires expression of G(M1), and in the case of SCLC cell lines the presence of G(M1) is sufficient. In NSCLC cell lines, expression of G(M1) is not sufficient for growth inhibition by CT. These findings imply refractoriness to growth inhibition by cAMP in G(M1)(+), CT-resistant NSCLC cell lines and the possibility of non-cAMP-related mechanisms for growth inhibition in CT-sensitive cell lines. C1 NCI,BIOL CHEM LAB,USN,MED ONCOL BRANCH,BLDG 37,RM 5D02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. RI Laborda, Jorge/L-5726-2014 OI Laborda, Jorge/0000-0002-9210-838X NR 28 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3340 EP 3346 PG 7 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400015 PM 1375868 ER PT J AU YOKOTA, T MILENIC, DE WHITLOW, M SCHLOM, J AF YOKOTA, T MILENIC, DE WHITLOW, M SCHLOM, J TI RAPID TUMOR PENETRATION OF A SINGLE-CHAIN FV AND COMPARISON WITH OTHER IMMUNOGLOBULIN FORMS SO CANCER RESEARCH LA English DT Article ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; HUMAN-COLON; MODELING ANALYSIS; ESCHERICHIA-COLI; ATHYMIC MICE; BINDING; ANTIGEN; B72.3; PROTEIN; RADIOLOCALIZATION AB Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid plasma and whole body clearance, as compared to intact IgG or Ig fragments. One potential consequence of the rapid sFv pharmacokinetic properties was the reduced percentage of injected dose/g of the radiolabeled sFv found in the tumor throughout a range of time points. The present study was designed to define the tumor penetration properties of a radiolabeled sFv in comparison with other Ig forms. I-125-labeled sFv, Fab', F(ab')2, and IgG forms of monoclonal antibody CC49, directed against the human pancarcinoma antigen TAG-72, were used to target the LS-174T human colon carcinoma xenograft in athymic mice. At various time points after systemic Ig administration, quantitative autoradiographic analyses of surgically removed tumors were used to define the rate and degree of penetration of the various Ig forms. These studies revealed that most of the intact IgG delivered to the tumor was concentrated in the region of or immediately adjacent to vessels, while the sFv was more evenly distributed throughout the tumor mass. The distributions of the Fab' and F(ab')2 fragments showed intermediate penetration in a size-related manner. The sFv demonstrated maximum tumor penetration at 0.5 h postinjection, while the intact IgG reached an equivalent degree of penetration at 48 to 96 h postinjection. These studies thus reveal a greater degree of uptake throughout the tumor for the sFv than would be expected by gross analyses of percentage injected dose/g and demonstrate an extremely rapid tumor penetration of the sFv. These studies should aid in the rational design of potential applications of drug-, toxin-, and radionuclide-conjugated sFvs in cancer therapy. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. ENZON INC,GAITHERSBURG,MD 20877. NR 34 TC 642 Z9 671 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3402 EP 3408 PG 7 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400025 PM 1596900 ER PT J AU TRITSCHER, AM GOLDSTEIN, JA PORTIER, CJ MCCOY, Z CLARK, GC LUCIER, GW AF TRITSCHER, AM GOLDSTEIN, JA PORTIER, CJ MCCOY, Z CLARK, GC LUCIER, GW TI DOSE-RESPONSE RELATIONSHIPS FOR CHRONIC EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN A RAT-TUMOR PROMOTION MODEL - QUANTIFICATION AND IMMUNOLOCALIZATION OF CYP1A1 AND CYP1A2 IN THE LIVER SO CANCER RESEARCH LA English DT Article ID AH-RECEPTOR; 2-HYDROXYLASE ACTIVITY; TISSUE DISTRIBUTION; UNTREATED RATS; BINDING; CYTOCHROME-P-450; MICROSOMES; TCDD; 3-METHYLCHOLANTHRENE; LOCALIZATION AB The mechanisms responsible for the broad spectrum of effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are not entirely clear but seem to involve an initial interaction with the Ah receptor. A major uncertainty in risk assessment for TCDD is the lack of adequate dose-response relationships following chronic exposure to TCDD. Induction of cytochrome P-450 enzymes (CYP1A1 and CYP1A2) is one of the most sensitive responses to TCDD and its structural analogues. We have used a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats to evaluate dose-response relationships for induction of CYP1A1 and CYP1A2 in diethylnitrosamine-initiated as well as in noninitiated rats. After initiation with a single dose of diethylnitrosamine, TCDD was administered biweekly by p.o. gavage at doses equivalent to 3.5, 10.7, 35.7, and 125 ng/kg/day for 30 weeks. CYP1A1 and CYP1A2 concentrations were quantified in hepatic microsomes by radioimmunoassay and localized in hepatic tissue slices by immunohistochemical techniques. Radioimmunoassay data revealed a maximum induction of 200-fold for CYP1A1 and 10-fold for CYP1A2 and there were no statistically significant differences between initiated and noninitiated rats. Induction at the lowest dose (3.5 ng/kg/day) was 20-fold for CYP1A1 and 3-fold for CYP1A2. Mathematical analysis indicates that the best fit of the induction data are inconsistent with a threshold for this response. There was a linear relationship between administered dose and TCDD liver concentration over the entire dose range of the study. This indicates that induction of CYP1A2 does not significantly alter the distribution of TCDD in our chronic dosing regimen. Immunolocalization of CYP1A1 and CYP1A2 revealed the same localization and induction pattern for both isozymes in the cytoplasm of hepatocytes. However, the hepatic distribution pattern was not uniform with the most intense staining observed around central veins. These studies help to clarify dose-response relationships for dioxin-mediated effects and demonstrate different sensitivity of hepatocytes to the effects of TCDD. RP TRITSCHER, AM (reprint author), NIEHS,MD D4-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010; Goldstein, Joyce/A-6681-2012 OI Portier, Christopher/0000-0002-0954-0279; NR 50 TC 154 Z9 155 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3436 EP 3442 PG 7 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400030 PM 1596902 ER PT J AU SAEKI, T STROMBERG, K QI, CF GULLICK, WJ TAHARA, E NORMANNO, N CIARDIELLO, F KENNEY, N JOHNSON, GR SALOMON, DS AF SAEKI, T STROMBERG, K QI, CF GULLICK, WJ TAHARA, E NORMANNO, N CIARDIELLO, F KENNEY, N JOHNSON, GR SALOMON, DS TI DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION OF AMPHIREGULIN AND CRIPTO IN HUMAN NORMAL COLON AND COLORECTAL TUMORS SO CANCER RESEARCH LA English DT Article ID GROWTH FACTOR-ALPHA; CARCINOMA CELL-LINES; FACTOR RECEPTORS; MESSENGER-RNA; BREAST-CANCER; FACTOR-BETA; EXPRESSION; MODEL; GENE; ADENOCARCINOMAS AB Thirty-six primary human colorectal tumors, 43 noninvolved colon samples that were adjacent to either carcinomas or adenomas, 22 adenomas, and nine normal colon specimens were immunohistochemically examined for the presence and localization of two epidermal growth factor-related peptides, amphiregulin (AR) and cripto. Within the primary tumors, 18 (50%) showed moderate levels of AR expression. Approximately 60% of the tubular and tubulovillous adenomas were positive for AR expression, whereas only 15% of the adjacent, noninvolved colon mucosa expressed AR. A greater proportion of well-differentiated tumors (71%) were positive for AR expression than were poorly differentiated tumors (18%). All of the nine normal colon specimens were positive. Consequently, AR expression appeared to be associated with both normal and malignant epithelial cells that were more differentiated. The distribution of cripto expression was different. Seventy-nine % of the colon tumors expressed cripto with a frequency of expression that was approximately equivalent between well-differentiated and poorly differentiated tumors. Approximately 86% of the tubulovillous adenomas, but only 43% of the tubular adenomas, were positive for cripto expression. In contrast, whereas AR was expressed in normal colon specimens, none of these tissues expressed cripto, and only 12% of the noninvolved normal colon samples adjacent to tumors or adenomas were positive for cripto. Cripto expression therefore appeared related to neoplasia. These data suggest that AR and cripto may be functioning as potential autocrine and/or paracrine growth factors in the colon and that the differential expression of cripto may serve as a potential tumor marker for colonic carcinogenesis. C1 NCI,DIV CANC BIOL & DIAG,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON W12 0H8,ENGLAND. HIROSHIMA UNIV HOSP,SCH MED,DEPT PATHOL,MINAI KU,HIROSHIMA,JAPAN. NAPLES UNIV,FAC MED & CHIRURG 2,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 48 TC 139 Z9 141 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3467 EP 3473 PG 7 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400035 PM 1596904 ER PT J AU YANG, JH THRAVES, P DRITSCHILO, A RHIM, JS AF YANG, JH THRAVES, P DRITSCHILO, A RHIM, JS TI NEOPLASTIC TRANSFORMATION OF IMMORTALIZED HUMAN KERATINOCYTES BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN SO CANCER RESEARCH LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; EPITHELIAL-CELLS; MECHANISMS; CONVERSION; PROMOTION; TOXICITY; PROTEIN; DNA AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most powerful carcinogen ever tested in animals. Recent epidemiological studies have suggested its carcinogenic potential in humans. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus 12-simian virus 40 (Ad12-SV40) were transformed by exposures of TCDD equal to or greater than 0.1 nM for 2 wk. These transformed cells showed morphological alterations and induced carcinomas when transplanted into nude mice, whereas no such transformation phenotypes were observed with exposures of less than 0.1 nM for 2 wk. Primary human epithelial keratinocytes exposed to various concentrations of TCDD failed to show any evidence of transformation. Induction of aryl hydrocarbon hydroxylase activity was dose dependent, as was transformation. Thus, the carcinogenicity of TCDD in this human cell system appears to be an Ah receptor-mediated process. The present study represents the first evidence of neoplastic conversion of human cells exposed to this environmentally important chemical. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT RADIAT MED,WASHINGTON,DC 20007. NR 29 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3478 EP 3482 PG 5 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400037 PM 1596905 ER PT J AU ICHIKAWA, T ICHIKAWA, Y DONG, J HAWKINS, AL GRIFFIN, CA ISAACS, WB OSHIMURA, M BARRETT, JC ISAACS, JT AF ICHIKAWA, T ICHIKAWA, Y DONG, J HAWKINS, AL GRIFFIN, CA ISAACS, WB OSHIMURA, M BARRETT, JC ISAACS, JT TI LOCALIZATION OF METASTASIS SUPPRESSOR GENE(S) FOR PROSTATIC-CANCER TO THE SHORT ARM OF HUMAN CHROMOSOME-11 SO CANCER RESEARCH LA English DT Article ID RAS ONCOGENE; WILMS-TUMOR; EXPRESSION; ABILITY; PROBES; CELLS AB Previous studies using somatic cell hybridization of highly metastatic and nonmetastatic rat prostatic cancer cells demonstrated that the resultant hybrids were nonmetastatic if all of the parental chromosomes were retained. Somatic hybrid segregants which underwent nonrandom chromosomal losses reexpressed high metastatic ability. These results demonstrated that there are gene(s) the expression of which can suppress metastatic ability of prostatic cancer cells. To identify the location of homologous gene(s) in the human, specific human chromosomes were introduced into highly metastatic rat prostatic cancer cells using the microcell-mediated chromosome transfer. Introduction of human chromosome 11 into highly metastatic rat prostate cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells. Spontaneous deletion of portions of human chromosome 11 in some of the clones delineated the minimal portion of human chromosome 11 capable of suppressing prostatic cancer metastases as the region between 11p11.2-13 but not including the Wilms' tumor-1 locus. C1 JOHNS HOPKINS UNIV,CTR ONCOL,SCH MED,BALTIMORE,MD 21231. JOHNS HOPKINS UNIV,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,BALTIMORE,MD 21205. TOTTORI UNIV,SCH LIFE SCI,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI 683,JAPAN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [2P30CA06973-29] NR 20 TC 122 Z9 125 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3486 EP 3490 PG 5 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400039 PM 1596907 ER PT J AU BLANEY, SM BALIS, FM GREM, J COLE, DE ADAMSON, PC POPLACK, DG AF BLANEY, SM BALIS, FM GREM, J COLE, DE ADAMSON, PC POPLACK, DG TI MODULATION OF THE CYTOTOXIC EFFECT OF CYCLOPENTENYLCYTOSINE BY ITS PRIMARY METABOLITE, CYCLOPENTENYLURIDINE SO CANCER RESEARCH LA English DT Article ID ANTITUMOR; CYTOSINE AB Cyclopentenylcytosine (CPE-C), a synthetic cytidine analogue with significant preclinical antitumor activity against both solid tumor xenografts and 1-beta-D-arabinofuranosylcytosine resistant murine leukemia cell lines, will soon enter phase I clinical trials. Unlike 1-beta-arabinofuranosylcytosine which is activated by deoxycytidine kinase, the enzyme responsible for the phosphorylation of CPE-C is uridine/cytidine kinase. Preclinical pharmacokinetic studies of CPE-C in nonhuman primates revealed that the primary route of elimination in this species was deamination to cyclopentenyluridine (CPE-U), an inhibitor of uridine/cytidine kinase. Since CPE-C is likely to be deaminated in humans, we investigated the modulating effect of CPE-U on the in vitro cytotoxicity of CPE-C in Molt-4 lymphoblasts. Concurrent exposure of cells to cytotoxic concentrations of CPE-C and 50-mu-M CPE-U resulted in the rescue of 50% of cells and exposure to CPE-U concentrations in excess of 100-mu-M resulted in the rescue of greater than 90% of cells. Progressive attenuation of the rescue effect was observed with delayed administration of CPE-U and no cells were rescued when addition of CPE-C was delayed for more than 2 h. At the intracellular level it was observed that the formation of the cytotoxic metabolite, cyclopentenylcytosine triphosphate, was blocked by increasing concentrations of CPE-U presumably secondary to inhibition of uridine/cytidine kinase by CPE-U. Although CPE-U can modulate the cytotoxic effects of CPE-C in vitro, the minimum CPE-U levels that are required for modulation coupled with the available preclinical pharmacokinetic data from nonhuman primates suggests that this modulation is not likely to impact on the antitumor effects of CPE-C in humans. C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NCI,NATL NAVAL MED CTR,MED ONCOL BRANCH,BETHESDA,MD 20899. RP BLANEY, SM (reprint author), NCI,PEDIAT BRANCH,BLDG 10,RM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1992 VL 52 IS 12 BP 3503 EP 3505 PG 3 WC Oncology SC Oncology GA HY054 UT WOS:A1992HY05400043 PM 1596909 ER PT J AU MEDDA, S PROIA, RL AF MEDDA, S PROIA, RL TI THE CARBOXYLESTERASE FAMILY EXHIBITS C-TERMINAL SEQUENCE DIVERSITY REFLECTING THE PRESENCE OR ABSENCE OF ENDOPLASMIC-RETICULUM-RETENTION SEQUENCES SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID RAT-LIVER; NUCLEOTIDE-SEQUENCE; ER PROTEINS; ESTERASE; CDNA; IDENTIFICATION; MEMBRANE; CLONING; YEAST AB Resident proteins of the endoplasmic reticulum lumen are continuously retrieved from an early Golgi compartment by a receptor-mediated mechanism. The sorting or retention sequence on the endoplasmic reticulum proteins is located at the C-terminus and was initially shown to be the tetrapeptide KDEL in mammalian cells and HDEL in Saccharomyces cerevisiae. The carboxylesterases are a large family of enzymes primarily localized to the lumen of the endoplasmic reticulum. Retention sequences in these proteins have been difficult to identify due to atypical and heterogeneous C-terminal sequences. Utilizing the polymerase chain reaction with degenerate primers, we have identified and characterized the C-termini of four members of the carboxylesterase family from rat liver. Three of the carboxylesterases sequences contained C-terminal sequences (HVEL, HNEL or HTEL) resembling the yeast sorting signal which were reported to be non-functional in mammalian cells. A fourth carboxylesterase contained a distinct C-terminal sequence, TEHT. A full-length esterase cDNA clone, terminating in the sequence HVEL, was isolated and was used to assess the retention capabilities of the various esterase C-terminal sequences. This esterase was retained in COS-1 cells, but was secreted when its C-terminal tetrapeptide, HVEL, was deleted. Addition of C-terminal sequences containing HNEL and HTEL resulted in efficient retention. However, the C-terminal sequence containing TEHT was not a functional retention signal. Both HDEL, the authentic yeast retention signal, and KDEL were efficient retention sequences for the esterase. These studies show that some members of the rat liver carboxylesterase family contain novel C-terminal retention sequences that resemble the yeast signal. At least one member of the family does not contain a C-terminal retention signal and probably represents a secretory form. C1 NIDDKD,GENET & BIOCHEM BRANCH,BLDG 10,ROOM 9D-15,BETHESDA,MD 20892. RI Proia, Richard/A-7908-2012 NR 28 TC 36 Z9 37 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN 15 PY 1992 VL 206 IS 3 BP 801 EP 806 DI 10.1111/j.1432-1033.1992.tb16987.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY404 UT WOS:A1992HY40400023 PM 1606962 ER PT J AU LEIKINA, E ONARAN, HO ZIMMERBERG, J AF LEIKINA, E ONARAN, HO ZIMMERBERG, J TI ACIDIC PH INDUCES FUSION OF CELLS INFECTED WITH BACULOVIRUS TO FORM SYNCYTIA SO FEBS LETTERS LA English DT Article DE MEMBRANE FUSION; VIRAL FUSION; ENVELOPED VIRUS; CELL-CELL FUSION; BACULOVIRUS EXPRESSION SYSTEM ID MEMBRANE-FUSION; INSECT CELLS; VIRUS; VECTOR; HEMAGGLUTININ; EXPRESSION; PROTEIN AB The enveloped baculovirus/insect cell system has been used extensively for expression of recombinant proteins, including viral fusion proteins. We tested wild-type baculovirus for endogenous fusion protein activity. Syncytia formation, dye transfer, and capacitance changes were observed after incubating infected Spodoptera frugiperda cells in acidic media, consistent with fusion protein activity. Only a short acidic pulse of 10 s is needed to trigger syncytia formation. Identical results were obtained with recombinant baculovirus. This new system is convenient for studying pH activated cell-cell fusion. However, using this enveloped virus to study the mechanism of recombinant fusion proteins requires caution. C1 NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 6C101,BETHESDA,MD 20892. NR 13 TC 42 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 15 PY 1992 VL 304 IS 2-3 BP 221 EP 224 DI 10.1016/0014-5793(92)80623-O PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JA748 UT WOS:A1992JA74800026 PM 1618326 ER PT J AU LELONG, IH PADMANABHAN, R LOVELACE, E PASTAN, I GOTTESMAN, MM AF LELONG, IH PADMANABHAN, R LOVELACE, E PASTAN, I GOTTESMAN, MM TI ATP AND GTP AS ALTERNATIVE ENERGY-SOURCES FOR VINBLASTINE TRANSPORT BY P-170 IN KB-V1 PLASMA-MEMBRANE VESICLES SO FEBS LETTERS LA English DT Article DE MULTIDRUG RESISTANCE; UPTAKE; VESICLE ID MULTIDRUG RESISTANCE; DEPENDENT TRANSPORT; CELL-LINES; BINDING AB Purified plasma membrane vesicles isolated from multidrug-resistant human KB-V1 cells accumulate [H-3]vinblastine in an energy-dependent manner. The accumulation of [H-3]vinblastine in the presence of ATP is a saturable process. ATP can be replaced by other purine nucleotide triphosphates, of which GTP is the most efficient. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 17 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 15 PY 1992 VL 304 IS 2-3 BP 256 EP 260 DI 10.1016/0014-5793(92)80632-Q PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JA748 UT WOS:A1992JA74800035 PM 1352260 ER PT J AU WANGE, RL KONG, ANT SAMELSON, LE AF WANGE, RL KONG, ANT SAMELSON, LE TI A TYROSINE-PHOSPHORYLATED 70-KDA PROTEIN BINDS A PHOTOAFFINITY ANALOG OF ATP AND ASSOCIATES WITH BOTH THE ZETA-CHAIN AND CD3 COMPONENTS OF THE ACTIVATED T-CELL ANTIGEN RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MONOCLONAL-ANTIBODIES; SURFACE-ANTIGENS; SUBUNIT; COMPLEX; LYMPHOCYTES; KINASE AB An early event in T cell antigen receptor (TCR)-mediated signal transduction is the activation of a protein tyrosine kinase (PTK) pathway. An unidentified PTK activity and a kinase substrate termed ZAP-70 have previously been shown to associate with TCR-zeta upon cross-linking of TCR-beta. Here we report that TCR activation, by antibody cross-linking of either TCR-beta or CD3-epsilon, results in the association of a PTK activity with both CD3 and TCR-zeta. A number of in vitro PTK substrates are also associated with CD3 and TCR-zeta, including CD3-epsilon, TCR-zeta, p60fyn, p62yes, and a predominant 70-kDa protein (ZAP-70). The shared PTK activity and PTK substrates suggest that both CD3 and TCR-zeta are involved in signal transduction via a shared pathway. We used [alpha-P-32]gamma-azidoanilido ATP, a photoreactive analogue of ATP, to detect CD3-associated proteins that bound ATP upon TCR activation, reasoning that such proteins could represent PTKs. A 70-kDa protein bound [alpha-P-32]gamma-azidoanilido ATP only upon TCR activation, and we propose that this protein and the 70-kDa PTK substrate are the same protein. Furthermore, we propose that this protein is responsible for the PTK activity observed to be associated with TCR-zeta and CD3 upon TCR activation. RP WANGE, RL (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 26 TC 147 Z9 147 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1992 VL 267 IS 17 BP 11685 EP 11688 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY947 UT WOS:A1992HY94700007 PM 1534800 ER PT J AU NEWTON, DL WALES, R RICHARDSON, PT WALBRIDGE, S SAXENA, SK ACKERMAN, EJ ROBERTS, LM LORD, JM YOULE, RJ AF NEWTON, DL WALES, R RICHARDSON, PT WALBRIDGE, S SAXENA, SK ACKERMAN, EJ ROBERTS, LM LORD, JM YOULE, RJ TI CELL-SURFACE AND INTRACELLULAR FUNCTIONS FOR RICIN GALACTOSE BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-SYNTHESIS INACTIVATION; CHAIN-CONTAINING IMMUNOTOXINS; B-CHAIN; A-CHAIN; INTERNALIZED RICIN; GOLGI-APPARATUS; ANTIBODY; MACROPHAGES; SITE; RECEPTORS AB The role of the two galactose binding sites of ricin B chain in ricin toxicity was evaluated by studying a series of ricin point mutants. Wild-type (WT) ricin and three ricin B chain point mutants having mutations in either 1) the first galactose binding domain (site 1 mutant, Met in place of Lys-40 and Gly in place of Asn-46), 2) the second galactose binding domain (site 2 mutant, Gly in place of Asn-255), or 3) both galactose binding domains (double site mutant containing all three amino acid replacements formerly stated) were expressed in Xenopus oocytes and then reassociated with recombinant ricin A chain. The different ricin B chains were mannosylated to the same extent. Cytotoxicity of these toxins was evaluated when cell entry was mediated either by galactose-containing receptors or through an alternate receptor, the mannose receptor of macrophages. WT ricin and each of the single domain mutants was able to kill Vero cells following uptake by galactose containing receptors. Lactose blocked the toxicity of each of these ricins. Site 1 and 2 mutants were 20-40 times less potent than WT ricin, and the double site mutant had no detectable cytotoxicity. WT ricin, the site 1 mutant, and the site 2 mutant also inhibited protein synthesis of mannose receptor-containing cells. Ricin can enter these cells through either a cell-surface galactose-containing receptor or through the mannose receptor. By including lactose in the cell medium, galactose-containing receptor-mediated uptake is blocked and cytotoxicity occurs solely via the mannose receptor. WT ricin, site 1, and site 2 mutants were cytotoxic to macrophages in the presence of lactose with the relative potency, WT > site 2 mutant> site 1 mutant. The double site mutant lacked cytotoxicity either in the absence or presence of lactose. Thus, even for mannose receptor-mediated toxicity of ricin, at least one galactose binding site remains necessary for cytotoxicity and two galactose binding sites further increases potency. These results are consistent with the model that the ricin B chain galactose binding activity plays a role not only in cell surface binding but also intracellularly for ricin cytotoxicity. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. UNIV WARWICK,DEPT BIOL SCI,COVENTRY CV4 7AL,W MIDLANDS,ENGLAND. RP NEWTON, DL (reprint author), NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892, USA. OI Saxena, Shailendra K/0000-0003-2856-4185 NR 45 TC 71 Z9 71 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 JUN 15 PY 1992 VL 267 IS 17 BP 11917 EP 11922 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY947 UT WOS:A1992HY94700042 PM 1601861 ER PT J AU SEBAG, M HENDERSON, J RHIM, J KREMER, R AF SEBAG, M HENDERSON, J RHIM, J KREMER, R TI RELATIVE RESISTANCE TO 1,25-DIHYDROXYVITAMIN-D3 IN A KERATINOCYTE MODEL OF TUMOR PROGRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-MYC GENE; FACTOR-ALPHA; CELLS; DIFFERENTIATION; RECEPTOR; GROWTH; DNA; INHIBITION; EXPRESSION; ONCOGENES AB We have examined the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on mitogen-stimulated growth and on c-myc proto-oncogene expression in a keratinocyte model of tumor progression. A dose-dependent inhibition of cell growth by 1,25-(OH)2D3 was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells. However, this inhibition was observed with the addition of 1,25-(OH)2D3 at a higher concentration in HPK1A-ras cells than in HPK1A cells. Cell cycle analysis revealed a blockage of the normal progression of the cell cycle from G0 to S phase in the presence of 1,25-(OH)2D3. A higher concentration of 1,25-(OH)2D3 was required in HPK1A-ras cells to overcome the mitogen-stimulated progression into S phase, when compared with HPK1A cells. Analysis of c-myc messenger RNA revealed a strong inhibition of its expression at early time points with higher concentrations of 1,25-(OH)2D3 being required to obtain an inhibition in HPK1A-ras cells similar to that obtained in HPK1A cells. 1,25-(OH)2D3 receptor characterization by sucrose gradient analysis and equilibrium binding demonstrated the presence of a single 3.7 S protein with similar receptor numbers and affinity in both cell lines. These observations therefore demonstrate that an alteration of the growth inhibitory response to 1,25-(OH)2D3 occurs when keratinocytes acquire the malignant phenotype and suggest that the alteration lies beyond the interaction of the ligand with its receptor. In addition, relative resistance to 1,25-(OH)2D3 was also observed in the expression of the cell-cycle associated oncogene c-myc. These studies may therefore have important implications in vivo in the development and growth of epithelial cell cancers. C1 MCGILL UNIV,DEPT MED,MONTREAL H3A 1A1,QUEBEC,CANADA. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20812. NR 41 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1992 VL 267 IS 17 BP 12162 EP 12167 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY947 UT WOS:A1992HY94700076 PM 1318311 ER PT J AU LUDWIG, T RUTHER, U METZGER, R COPELAND, NG JENKINS, NA LOBEL, P HOFLACK, B AF LUDWIG, T RUTHER, U METZGER, R COPELAND, NG JENKINS, NA LOBEL, P HOFLACK, B TI GENE AND PSEUDOGENE OF THE MOUSE CATION-DEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR - GENOMIC ORGANIZATION, EXPRESSION, AND CHROMOSOMAL LOCALIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-II; ALPHA-AMYLASE GENE; TRANSCRIPTION FACTOR; LYSOSOMAL-ENZYMES; BINDING-PROTEIN; CELLS; CLONING; SEQUENCES; CDNA; RNA AB The cation-dependent mannose 6-phosphate receptor (CD-MPR) is one of the two transmembrane proteins involved in transport of lysosomal enzymes. We have cloned the mouse CD-MPR gene and also a very unusual processed-type CD-MPR pseudogene. They are both present at one copy per haploid genome and map to chromosomes 6 and 3, respectively. Comparison of the complete 10-kilobase (kb) sequence of the functional gene with the cDNA indicates that it contains seven exons. Exon 1 encodes the 5'-untranslated region of the mRNA, the others (exons 2-7) encode the luminal, transmembrane, and cytoplasmic domains of the CD-MPR. Exon 7 also contains a 1.2-kb-long 3'-untranslated region of the mRNA. A unique transcription-initiation site was determined by primer extension of mouse liver mRNA. The promoter elements in the 5' upstream region of this site resemble those contained in genes constitutively transcribed. However, Northern blot analysis demonstrates that the CD-MPR is variably expressed in adult mouse tissues and during mouse development. The pseudogene, which is flanked by direct repeats, is almost colinear with the cDNA indicating that it presumably arose by reverse transcription of an mRNA. However, the pseudogene differs from the cDNA. It contains at its 5' end, an additional 340-nucleotide (nt) sequence homologous to the promoter region of the functional gene. This sequence exhibits some promoter activity in vitro. Furthermore, a 24-nt insertion interrupts the region homologous to the 5'-noncoding region of the cDNA. In the functional gene, this 24-nt sequence occurs between exon 1 and 2, where it is flanked by typical consensus sequences of exon/intron boundaries. Therefore, it may represent an additional exon of the functional gene. These two features of the pseudogene suggest that expression of the CD-MPR gene may be regulated by use of different promoters and/or alternative splicing. C1 UNIV HEIDELBERG,DEPT PHARMACOL,W-6900 HEIDELBERG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21701. CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. UNIV MED & DENT NEW JERSEY,PISCATAWAY,NJ 08854. RP LUDWIG, T (reprint author), EUROPEAN MOLEC BIOL LAB,DIFFERENTIAT PROGRAMME,POSTFACH 102209,MEYERHOFSTR 1,W-6900 HEIDELBERG,GERMANY. RI Ludwig, Thomas/Q-6484-2016 OI Ludwig, Thomas/0000-0003-3461-2585 FU NCI NIH HHS [N01-CO-74101] NR 49 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1992 VL 267 IS 17 BP 12211 EP 12219 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY947 UT WOS:A1992HY94700084 PM 1376319 ER PT J AU THOMAS, PM SAMELSON, LE AF THOMAS, PM SAMELSON, LE TI THE GLYCOPHOSPHATIDYLINOSITOL-ANCHORED THY-1 MOLECULE INTERACTS WITH THE P60FYN PROTEIN TYROSINE KINASE IN T-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; CO-EXPRESSION; ACTIVATION; PHOSPHORYLATION; MEMBRANE; COMPLEX; ASSOCIATION; CHAIN AB Stimulation of murine T cells by engagement of the multi-component T cell antigen receptor or by cross-linking the Thy-1 molecule leads to a similar response characterized by lymphocyte activation and lymphokine production. The early biochemical events induced by engaging these molecules also are similar and begin with activation of a tyrosine kinase pathway and tyrosine phosphorylation of a comparable set of substrates. Previous work demonstrates that the protein tyrosine kinase p60(fyn) is associated with the antigen receptor and therefore it may participate in the tyrosine phosphorylations that are observed with antigen receptor signaling. In this study we demonstrate that the Thy-1 molecule is also associated with p60(fyn) in a murine T cell hybridoma and in murine thymocytes. The interaction is independent of antigen receptor expression. Thy-1 is a member of the class of molecules anchored to the plasma membrane by a glycophosphatidylinositol (GPI) group. The association of Thy-1 with p60(fyn) is dependent on the GPI linkage, since cleavage of the GPI anchor disrupts the interaction. The association of Thy-1 and p60(fyn) suggests a means by which Thy-1 cross-linking leads to tyrosine phosphorylation and T cell activation. RP THOMAS, PM (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 31 TC 206 Z9 207 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 1992 VL 267 IS 17 BP 12317 EP 12322 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY947 UT WOS:A1992HY94700099 PM 1351058 ER PT J AU OTTEN, GR BIKOFF, E RIBAUDO, RK KOZLOWSKI, S MARGULIES, DH GERMAIN, RN AF OTTEN, GR BIKOFF, E RIBAUDO, RK KOZLOWSKI, S MARGULIES, DH GERMAIN, RN TI PEPTIDE AND BETA-2-MICROGLOBULIN REGULATION OF CELL-SURFACE MHC CLASS-I CONFORMATION AND EXPRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; HLA-B-ANTIGENS; BREFELDIN-A; ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODIES; HEAVY-CHAINS; SERUM BETA-2-MICROGLOBULIN; TRANSPLANTATION ANTIGENS; GOLGI PROTEINS AB We have examined the roles of peptide and beta-2-microglobulin (beta-2m) in regulating the conformation and expression level of class I molecules on the cell surface. Using a cell line synthesizing H-2D(d) H chain and mouse beta-2m but defective in endogenous peptide loading, we demonstrate the ability of either exogenous peptide or beta-2m alone to increase surface H-2D(d) expression at both 25-degrees-C and 37-degrees-C. Peptide and beta-2m show marked synergy in their abilities to increase surface class I expression, with minimal increases promoted by peptide in the absence of free beta-2m. Low temperature-induced molecules have indistinguishable rates of loss of beta-2m and alpha-1/alpha-2 domain conformational epitopes during culture at 37-degrees-C. However, the rate of alpha-3 epitope loss is much slower, indicating a minimum of two steps in class I loss from the cell surface: 1) loss of beta-2m binding to H chain and unfolding of the alpha-1/alpha-2 region; then 2) denaturation, degradation, or internalization of the free H chains possessing alpha-3 epitopes. These data show for the first time that free H chains survive for a finite time on the membrane in a form capable of refolding into alpha-1/alpha-2 epitope positive molecules upon addition of beta-2m and peptide. This refolding in the presence of beta-2m and peptide can explain the reported requirement for both components in sensitizing cells for class I-dependent CTL lysis. It also indicates that such conformational changes in class I molecules are not strictly dependent on either newly synthesized H chains or on intracellular chaperons. The study of H chain-peptide-beta-2m interaction on the cell surface may be relevant to understanding intracellular peptide loading events. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BLDG 10,ROOM 11N311,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,DEPT OBSTET & GYNECOL,NEW YORK,NY 10029. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NICHD NIH HHS [HD-25926] NR 64 TC 127 Z9 131 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1992 VL 148 IS 12 BP 3723 EP 3732 PG 10 WC Immunology SC Immunology GA HY056 UT WOS:A1992HY05600006 PM 1602127 ER PT J AU ABRAHAM, VS SACHS, DH SYKES, M AF ABRAHAM, VS SACHS, DH SYKES, M TI MECHANISM OF PROTECTION FROM GRAFT-VERSUS-HOST DISEASE MORTALITY BY IL-2 .3. EARLY REDUCTIONS IN DONOR T-CELL SUBSETS AND EXPANSION OF A CD3+CD4-CD8- CELL-POPULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL SUPPRESSOR CELLS; ACTIVATED KILLER CELLS; BONE-MARROW; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; INTERLEUKIN-2; RECIPIENTS; REJECTION; LEUKEMIA; ANTIGEN AB Reducing the graft-vs-host disease (GVHD)-promoting capacity of allogeneic T cells while maintaining alloengraftment and graft-vs-leukemia effects remains an important but elusive goal in clinical bone marrow transplantation (BMT). We have recently demonstrated that a short course of high dose IL-2 administered at the time of BMT has a powerful protective effect against GVHD mortality in mice. This short course of IL-2 is able to protect mice from both acute and chronic GVHD without sacrificing alloengraftment or graft-vs-leukemia effects of allogeneic T cells. Because the early administration of IL-2 seems to be crucial for this effect, we have studied the early lymphoid repopulation events after lethal irradiation and allogeneic BMT. These studies show that there are consistent delays in splenic repopulation by allogeneic cells after BMT in IL-2-treated animals compared with their untreated cohorts. Even greater percent reductions were seen in donor splenic T cell populations in the first few days after BMT in IL-2-treated animals. Splenic cells with the CD3+CD4-CD8- phenotype were increased in IL-2 treated animals at days 3 and 4 after BMT. This phenotype resembles that of bone marrow-derived cells which have been previously shown to inhibit GVHD, suggesting a possible mechanism for the protective effect of IL-2. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP E,SCH MED,TRANSPLANTAT BIOL RES CTR,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI 31158-01] NR 33 TC 39 Z9 40 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1992 VL 148 IS 12 BP 3746 EP 3752 PG 7 WC Immunology SC Immunology GA HY056 UT WOS:A1992HY05600009 PM 1534824 ER PT J AU MURPHY, WJ DURUM, SK ANVER, MR LONGO, DL AF MURPHY, WJ DURUM, SK ANVER, MR LONGO, DL TI IMMUNOLOGICAL AND HEMATOLOGIC EFFECTS OF NEUROENDOCRINE HORMONES - STUDIES ON DW/J DWARF MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-HORMONE; SOMATOMEDIN-C; SNELL AB DW/J dwarf mice lack acidophilic anterior pituitary cells and are deficient in growth hormone and other neuroendocrine mediators. These mice were examined to determine the effects of these deficiencies on hematopoietic and immune system development. Previous studies have suggested that these mice had immunologic defects primarily involving T cell development. However, we have found that these mice exhibit decreased peripheral blood cell counts affecting all lineages (erythrocytic, leukocytic, and platelets). Examination of lymphoid tissues of dwarf mice indicated that their spleens were hypoplastic. Treatment of these mice with recombinant human growth hormone resulted in a significant improvement of peripheral blood counts and spleen cell number. Analysis of the bone marrow indicated a profound deficiency of B cell progenitors in the dwarf mice. However, in untreated dwarf mice, mature B cells and T cells were observed in the spleens. Although treatment with recombinant human growth hormone could correct the hematopoietic deficiencies in these mice, it did not restore the B cell progenitor populations, suggesting that an absence of growth hormone is not solely responsible for this deficiency. Thus, these mice display significant myeloid and lymphoid deficiencies that have been previously undetected. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-74102] NR 19 TC 117 Z9 117 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1992 VL 148 IS 12 BP 3799 EP 3805 PG 7 WC Immunology SC Immunology GA HY056 UT WOS:A1992HY05600016 PM 1602129 ER PT J AU EHRHARDT, RO STROBER, W HARRIMAN, GR AF EHRHARDT, RO STROBER, W HARRIMAN, GR TI EFFECT OF TRANSFORMING GROWTH-FACTOR (TGF)-BETA-1 ON IGA ISOTYPE EXPRESSION - TGF-BETA-1 INDUCES A SMALL INCREASE IN SIGA+ B-CELLS REGARDLESS OF THE METHOD OF B-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR-BETA; LYMPHOCYTES-B; LIPOPOLYSACCHARIDE; DIFFERENTIATION; FACTOR-BETA-1; PROLIFERATION AB Transforming growth factor-beta (TGF-beta) has been reported to play an important role in IgA isotype expression when B cells are stimulated with LPS. The goal of the present study was to determine whether TGF-beta has similar effects on IgA isotype expression under more physiologic conditions utilizing a variety of B cell activation systems. As previously reported, in the LPS system TGF-beta caused a small, but significant, absolute increase in surface IgA (sIgA) expression and a very definite increase in IgA secretion; these effects were enhanced by IL-2 and IL-5. In the case of B cell stimulation with another B cell stimulant, the thymus-independent type II mitogen, anti-IgD-dextran, TGF-beta led to a similar small increase in sIgA expression, but caused suppression of IgA secretion. Using the Th2 cell clones CDC35 and D10 to stimulate resting B cells in a cognate and non-cognate T cell-dependent fashion, respectively, TGF-beta again increased sIgA expression to a similar small extent. TGF-beta at low doses (0.1 ng/ml) did not increase IgA secretion significantly and, at higher doses (1.0 ng/ml) caused significant suppression of IgA secretion. Addition of various cytokines (IL-2, -4, -5, D10sup) other than TGF-beta to stimulated B cells did not increase sIgA expression, but did give rise to increased amounts of IgA secretion, especially when activated D10 T cells were used as the B cell stimulant. Finally, the addition of an antibody against TGF-beta to cultures containing TGF-beta on day 2 led to partial or complete reversal of the inhibitory effects of TGF-beta on IgA secretion. In conclusion, TGF-beta causes a consistent, but small increase in sIgA+ B cells, in cultures of B cells stimulated by a variety of T cell-dependent or independent stimuli. In contrast, TGF-beta either promotes or inhibits B cell survival and IgA secretion, depending on the method of B cell activation. These results are most consistent with the view that TGF-beta provides only a partial or incomplete IgA switch signal but that additional factors are involved in IgA isotype switching and differentiation. RP EHRHARDT, RO (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N250,BETHESDA,MD 20892, USA. NR 23 TC 67 Z9 70 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1992 VL 148 IS 12 BP 3830 EP 3836 PG 7 WC Immunology SC Immunology GA HY056 UT WOS:A1992HY05600020 PM 1602131 ER PT J AU MONGINI, PKA BLESSINGER, CA HIGHET, PF INMAN, JK AF MONGINI, PKA BLESSINGER, CA HIGHET, PF INMAN, JK TI MEMBRANE IGM-MEDIATED SIGNALING OF HUMAN B-CELLS - EFFECT OF INCREASED LIGAND-BINDING SITE VALENCY ON THE AFFINITY AND CONCENTRATION REQUIREMENTS FOR INDUCING DIVERSE STAGES OF ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SURFACE-IMMUNOGLOBULIN; INDEPENDENT ANTIGENS; LYMPHOCYTES-B; ANTIBODIES; PROLIFERATION; TOLERANCE; MODEL; DIFFERENTIATION; IMMUNOGENICITY; POPULATIONS AB The potential for ligand-initiated signal transduction through B cell membrane IgM is assessed in terms of ligand concentration, binding site valency, and binding site affinity for membrane Ig. Estimates of the physicochemical requirements for achieving G0* enhancement of class II MHC expression, G1 entry, and S phase entry in human B cells were made by comparing the stimulatory effects of three affinity-diverse anti-C-mu-2 mAb when in bivalent (unconjugated) form, or as mAb-dextran conjugates with low binding site valency (oligovalent ligands) or high binding site valency (multivalent ligands). An increase in binding site number (and concomitant molecular mass) caused a profound reduction in both the minimal concentration and affinity requisites for B cell activation. The enhancing effect of increased binding site valency was most evident for the signaling of those most distal stages in B cell activation, i.e., G1 and S phase, which were difficult to induce with bivalent ligands. The results suggest that highly multimeric TI-2 Ag may be good immunogens because they are able to elicit a full activation response not only from infrequent high affinity B cells, but also from a substantial proportion of the many lower affinity Ag-specific B cells in virgin B cell populations. Interestingly, the activation of B cells by ligands with binding sites of high intrinsic affinity (K(a) = 5 x 10(8) M-1) was less influenced by increases in binding site valency than was B cell activation by ligands with intermediate binding site affinity (K(a) = 2 x 10(7) M-1). This suggests that the minimal epitope valency requirement for T cell-independent B cell activation by mIg cross-linking Ag may be dependent on the intrinsic affinity with which membrane Ig molecules on a given B cell interact with the redundantly expressed epitopes. C1 NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,DEPT PATHOL,NEW YORK,NY 10016. NIH,IMMUNOL LAB,BETHESDA,MD 20892. RP MONGINI, PKA (reprint author), HOSP JOINT DIS & MED CTR,DEPT RHEUMAT DIS,301 E 17TH ST,NEW YORK,NY 10003, USA. FU NIGMS NIH HHS [GM-35174] NR 51 TC 41 Z9 42 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1992 VL 148 IS 12 BP 3892 EP 3901 PG 10 WC Immunology SC Immunology GA HY056 UT WOS:A1992HY05600028 PM 1376344 ER PT J AU HILLMAN, K QIAN, JH SIEGEL, JN RODERIQUEZ, G BLACKBURN, R MANISCHEWITZ, J NORCROSS, M GOLDING, H AF HILLMAN, K QIAN, JH SIEGEL, JN RODERIQUEZ, G BLACKBURN, R MANISCHEWITZ, J NORCROSS, M GOLDING, H TI REDUCED SUSCEPTIBILITY TO HIV-1 INFECTION OF ETHYL-METHANESULFONATE-TREATED CEM SUBCLONES CORRELATES WITH A BLOCKADE IN THEIR PROTEIN-KINASE-C SIGNALING PATHWAY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; T-CELL ACTIVATION; NECROSIS FACTOR-ALPHA; GENE-EXPRESSION; TRANSCRIPTION FACTOR; ANTIGEN RECEPTOR; NUCLEAR-PROTEIN; PHORBOL ESTERS; HTLV-III/LAV AB We have described the isolation of chemically induced CEM subclones that express CD4 receptors and bind soluble gp120, yet show a markedly reduced susceptibility to infection with HIV-1. Two subclones were found to have an abnormal response to the protein kinase C (PKC) activator PMA. PMA treatment induced CD3 and CD25 (IL-2R) receptors on the parental line and on other ethyl-methanesulfonate-derived subclones, but not on these two mutants. Direct assays of PKC activity were conducted. Total cellular PKC enzymatic activity was found to be normal in these subclones. PMA-induced CD4 down-modulation occurred normally. In addition, activation of c-raf kinase was normal. Since HIV-1 long terminal repeat contains two functional nuclear factor kB (NF-kB) regulatory elements, we studied the ability of PMA to induce NF-kB binding activity by different assays. Chloramphenicol acetyl transferase (CAT) assays using the HIV-1 (-139)long terminal repeat-CAT construct showed no PMA induction of CAT activity in these subclones (unlike the parental line and other subclones). Okadaic acid, an inhibitor of phosphatases 1 and 2A, did not overcome the defect in these subclones. Gel retardation assays, using a P-32-probe containing the HIV-1 NF-kB probe and nuclear extracts from PMA-treated cells, showed significantly reduced induction of nuclear NF-kB binding proteins in these two subclones compared with wild type CEM and a control subclone. Deoxycholate treatment of cytoplasmic extracts from these subclones released much reduced NF-kB binding proteins from their cytoplasmic pools. Thus, reduced levels of PKC-induced nuclear NF-kB activity in two T cell subclones did not affect their normal cell growth, but correlated with a pronounced reduction in their susceptibility to HIV-1 infection. C1 US FDA, CBER,DIV VIROL,FDA BLDG 29A,ROOM 2C15, HFB 555,8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. US FDA, CBER, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NR 45 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1992 VL 148 IS 12 BP 3991 EP 3998 PG 8 WC Immunology SC Immunology GA HY056 UT WOS:A1992HY05600041 PM 1351090 ER PT J AU VUISTER, GW BAX, A AF VUISTER, GW BAX, A TI RESOLUTION ENHANCEMENT AND SPECTRAL EDITING OF UNIFORMLY C-13-ENRICHED PROTEINS BY HOMONUCLEAR BROAD-BAND C-13 DECOUPLING SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID 3D NMR-SPECTROSCOPY; LINEAR PREDICTION; 2D; PHASE; EXTRAPOLATION; MAGNETIZATION; ASSIGNMENT; H-1 RP VUISTER, GW (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 25 TC 411 Z9 412 U1 0 U2 12 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD JUN 15 PY 1992 VL 98 IS 2 BP 428 EP 435 DI 10.1016/0022-2364(92)90144-V PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA HZ623 UT WOS:A1992HZ62300016 ER PT J AU BULDYREV, SV BARABASI, AL CASERTA, F HAVLIN, S STANLEY, HE VICSEK, T AF BULDYREV, SV BARABASI, AL CASERTA, F HAVLIN, S STANLEY, HE VICSEK, T TI ANOMALOUS INTERFACE ROUGHENING IN POROUS-MEDIA - EXPERIMENT AND MODEL SO PHYSICAL REVIEW A LA English DT Note ID GROWTH AB We report measurements of the interface formed when a wet front propagates in paper by imbibition and we find anomalous roughening with exponent-alpha = 0.63 +/- 0.04. We also formulate an imbibition model that agrees with the experimental morphology. The main ingredient of the model is the propagation and pinning of a self-affine interface in the presence of quenched disorder, with erosion of overhangs. By relating our model to directed percolation, we find alpha congruent-to 0.63. C1 BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. EOTVOS LORAND UNIV,DEPT ATOM PHYS,H-1445 BUDAPEST,HUNGARY. RP BULDYREV, SV (reprint author), BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215, USA. RI Vicsek, Tamas/A-3305-2009; Buldyrev, Sergey/I-3933-2015 NR 22 TC 287 Z9 287 U1 3 U2 15 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD JUN 15 PY 1992 VL 45 IS 12 BP R8313 EP R8316 PG 4 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA JA214 UT WOS:A1992JA21400002 ER PT J AU LIPKOWITZ, S GARRY, VF KIRSCH, IR AF LIPKOWITZ, S GARRY, VF KIRSCH, IR TI INTERLOCUS V-J RECOMBINATION MEASURES GENOMIC INSTABILITY IN AGRICULTURE WORKERS AT RISK FOR LYMPHOID MALIGNANCIES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HYBRID ANTIGEN RECEPTOR GENES; LEUKEMIA; LYMPHOMA ID CELL RECEPTOR GENES; ATAXIA-TELANGIECTASIA; B-CELL; CHROMOSOME-14 INVERSION; REGION GENES; GAMMA-GENES; IMMUNOGLOBULIN; TRANSLOCATIONS; LYMPHOCYTES; DIVERSITY AB V(D)J [variable-(diversity)-joining] rearrangements occur between, as well as within, immune receptor loci, resulting in the generation of hybrid antigen-receptor genes and the formation of a variety of lymphocyte-specific chromosomal aberrations. Such hybrid genes occur at a low frequency in the peripheral blood lymphocytes (PBL) of normal individuals but show a markedly increased incidence in the PBL of individuals with the autosomal recessive disease ataxia-telangiectasia. In this manuscript we demonstrate that the frequency of hybrid antigen-receptor genes is 10- to 20-fold increased in the PBL of an occupational group, agriculture workers, with related environmental exposures. Both ataxia-telangiectasia patients and this population of agriculture workers are at increased risk for lymphoid malignancy. This result suggests that the measurement of hybrid antigen receptor-genes in PBL may be a sensitive assay for a type of lymphocyte-specific genomic instability. As a corollary, this assay may identify populations at risk of developing common types of lymphoid malignancy. C1 UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55414. RP LIPKOWITZ, S (reprint author), BETHESDA NAVAL HOSP,NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 36 TC 85 Z9 85 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5301 EP 5305 DI 10.1073/pnas.89.12.5301 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300021 PM 1608939 ER PT J AU SHIMIZU, YK IWAMOTO, A HIJIKATA, M PURCELL, RH YOSHIKURA, H AF SHIMIZU, YK IWAMOTO, A HIJIKATA, M PURCELL, RH YOSHIKURA, H TI EVIDENCE FOR INVITRO REPLICATION OF HEPATITIS-C VIRUS GENOME IN A HUMAN T-CELL LINE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CDNA; PCR ID NON-B-HEPATITIS; NON-A; DELTA-VIRUS; CHIMPANZEES; ANTIBODIES; POLYMERASE; ASSAY AB A human T-cell line, MOLT-4, either uninfected or infected with murine retroviruses, was tested for its susceptibility to hepatitis C virus (HCV) infection. The cell cultures were inoculated with a serum containing HCV and then examined for the presence of viral sequences by cDNA/PCR. In murine retrovirus-infected MOLT-4 (MOLT-4 Ma) cells, intracellular minus-strand viral RNA, a putative replication intermediate, was first detected 3 days after inoculation, and the maximum signal was seen on day 7. When the cells were continuously subcultured in fresh medium, HCV sequences were intermittently detected in cells over a period of 3 weeks. In MOLT-4 cells free of retroviruses, replication of minus-strand HCV RNA appeared less efficient than in MOLT-4 Ma cells. The presence of minus-strand viral RNA in MOLT-4 Ma cells inoculated with HCV was confirmed by in situ hybridization with a strand-specific RNA probe. Immunofluorescence tests with antibodies specific for HCV core and NS4 antigens showed that MOLT-4 Ma cells were positive for viral antigen 7 days after inoculation. Thus, it appears likely that the HCV genome can replicate in the human T-cell line MOLT-4. C1 UNIV TOKYO,FAC MED,DEPT BACTERIOL,TOKYO 113,JAPAN. NIH,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. RP SHIMIZU, YK (reprint author), NATL INST HLTH,DEPT ENTEROVIRUSES,MURAYAMA ANNEX,MUSASHIMURAYAMA,TOKYO 19012,JAPAN. NR 24 TC 307 Z9 310 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5477 EP 5481 DI 10.1073/pnas.89.12.5477 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300057 PM 1319062 ER PT J AU DEMCHYSHYN, L SUNAHARA, RK MILLER, K TEITLER, M HOFFMAN, BJ KENNEDY, JL SEEMAN, P VANTOL, HHM NIZNIK, HB AF DEMCHYSHYN, L SUNAHARA, RK MILLER, K TEITLER, M HOFFMAN, BJ KENNEDY, JL SEEMAN, P VANTOL, HHM NIZNIK, HB TI A HUMAN SEROTONIN 1D RECEPTOR VARIANT (5HT1D-BETA) ENCODED BY AN INTRONLESS GENE ON CHROMOSOME-6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POLYMERASE CHAIN REACTION; SUMATRIPTAN; GUANINE NUCLEOTIDE-BINDING PROTEIN; LIMBIC SYSTEM ID 5-HT1A RECEPTOR; MOLECULAR PHARMACOLOGY; FUNCTIONAL EXPRESSION; ADENYLATE-CYCLASE; BRAIN MEMBRANES; 5-HYDROXYTRYPTAMINE; BINDING; RAT; SUBTYPE; CLONING AB An intronless gene encoding a serotonin receptor (5HT1D-beta) has been cloned and functionally expressed in mammalian fibroblast cultures. Based on the deduced amino acid sequence, the gene encodes a 390-amino acid protein displaying considerable homology, within putative transmembrane domains (almost-equal-to 75% identity) to the canine and human 5HT1D receptors. Membranes prepared from CHO cells stably expressing the receptor bound [H-3]serotonin with high affinity (K(d) 4 nM) and displayed a pharmacological profile consistent, but not identical, with that of the characterized serotonin 5HTlD receptor. Most notably, metergoline and serotonergic piperazine derivatives, as a group, display 3- to 8-fold lower affinity for the 5HT1D-beta receptor than for the 5HT1D receptor, whereas both receptors display similar affinities for tryptamine derivatives, including the antimigraine drug sumatriptan. Northern blot analysis revealed an mRNA of almost-equal-to 5.5 kilobases expressed in human and monkey frontal cortex, medulla, striatum, hippocampus and amygdala but not in cerebellum, olfactory tubercle, and pituitary. The 5HT1D-beta gene maps to human chromosome 6. The existence of multiple neuronal 5HT1D-like receptors may help account for some of the complexities associated with [H-3]serotonin binding patterns in native membranes. C1 UNIV TORONTO,DEPT PSYCHIAT,TORONTO M5S 1A8,ONTARIO,CANADA. UNIV TORONTO,DEPT PHARMACOL,TORONTO M5S 1A8,ONTARIO,CANADA. UNION UNIV,DEPT PHARMACOL & TOXICOL,ALBANY,NY 12208. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. CLARKE INST PSYCHIAT,MOLEC GENET LAB,TORONTO M5T 1R8,ONTARIO,CANADA. CLARKE INST PSYCHIAT,MOLEC NEUROBIOL LAB,TORONTO M5T 1R8,ONTARIO,CANADA. FU NHLBI NIH HHS [HL07194]; NIDA NIH HHS [DA-07223-01]; NIMH NIH HHS [MH40716] NR 44 TC 101 Z9 104 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5522 EP 5526 DI 10.1073/pnas.89.12.5522 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300066 PM 1351684 ER PT J AU KRISHNA, MC GRAHAME, DA SAMUNI, A MITCHELL, JB RUSSO, A AF KRISHNA, MC GRAHAME, DA SAMUNI, A MITCHELL, JB RUSSO, A TI OXOAMMONIUM CATION INTERMEDIATE IN THE NITROXIDE-CATALYZED DISMUTATION OF SUPEROXIDE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ELECTRON PARAMAGNETIC RESONANCE; HYDROGEN PEROXIDE; SUPEROXIDE RADICAL; SUPEROXIDE DISMUTASE; OXOAMMONIUM CATION ID ELECTRON-SPIN-RESONANCE; RAT-LIVER; METABOLISM; LABELS; CELLS; REDUCTION; RADICALS; MICROSOMES; OXYGEN AB Dismutation of superoxide has been shown previously to be catalyzed by stable nitroxide compounds. In the present study, the mechanism of superoxide (.O2-) dismutation by various five-membered ring and six-membered ring nitroxides was studied by electron paramagnetic resonance spectrometry, UV-visible spectrophotometry, cyclic voltammetry, and bulk electrolysis. Electron paramagnetic resonance signals from the carbocyclic nitroxide derivatives (piperidinyl, pyrrolidinyl, and pyrrolinyl) were unchanged when exposed to enzymatically generated .O2-, whereas, in the presence of .O2- and reducing agents such as NADH and NADPH, the nitroxides underwent reduction to their respective hydroxylamines. The reaction of 4-hydroxy-2,2,6,6-tetramethyl-1-hydroxypiperidine (Tempol-H) with .O2- was measured and, in agreement with earlier reports on related compounds, the rate was found to be too slow to be consistent with a mechanism of .O2- dismutation involving the hydroxylamine as an intermediate. Voltammetric analyses of the carbocyclic nitroxide derivatives revealed a reversible one-electron redox couple at positive potentials. In contrast, oxazolidine derivatives were irreversibly oxidized. At negative potentials, all of the nitroxides studied exhibited a broad, irreversible reductive wave. The rate of .O2- dismutation correlated with the reversible midpoint redox potential. Bulk electrolysis at positive potentials was found to generate a metastable oxidized form of the nitroxide. The results indicate that the dismutation of .O2- is catalyzed by the oxoammonium/nitroxide redox couple for carbocyclic nitroxide derivatives. In addition to the one-electron mitochondrial reduction pathway, the present results suggest the possibility that cellular bioreduction by a two-electron pathway may occur subsequent to oxidation of stable nitroxides. Furthermore, the cellular destruction of persistent spin adduct nitroxides might also be facilitated by a primary univalent oxidation. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3 B69,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,IL-91010 JERUSALEM,ISRAEL. NR 36 TC 271 Z9 274 U1 3 U2 28 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5537 EP 5541 DI 10.1073/pnas.89.12.5537 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300069 PM 1319064 ER PT J AU EIDELMAN, O GUAYBRODER, C VANGALEN, PJM JACOBSON, KA FOX, C TURNER, RJ CABANTCHIK, ZI POLLARD, HB AF EIDELMAN, O GUAYBRODER, C VANGALEN, PJM JACOBSON, KA FOX, C TURNER, RJ CABANTCHIK, ZI POLLARD, HB TI A1 ADENOSINE-RECEPTOR ANTAGONISTS ACTIVATE CHLORIDE EFFLUX FROM CYSTIC-FIBROSIS CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CFPAC CELLS; XANTHINES ID LINE T84; EPITHELIUM; SECRETION; GENE; 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE; IDENTIFICATION; PERMEABILITY; CHANNELS; INVITRO; DISEASE AB A1 adenosine-receptor-antagonist drugs such as 8-cyclopentyl-1,3-dipropylxanthine (CPX) and xanthine amine congener (XAC) are found to activate the efflux of Cl-36 from CFPAC cells. These cells are a pancreatic adenocarcinoma cell line derived from a cystic fibrosis (CF) patient homozygous for the common mutation, deletion of Phe-508. The active concentrations for these compounds are in the low nanomolar range, consistent with action on A1 adenosine receptors. In addition, drug action can be blocked by exogenous agonists such as 2-chloroadenosine and also can be antagonized by removal of endogenous agonists by treatment with adenosine deaminase. Cells lacking the CF genotype and phenotype, such as HT-29 and T84 colon carcinoma cell lines, appear to be resistant to activation of chloride efflux by either drug. CFPAC cells transfected with the CF transmembrane regulator gene, CFTR, are also resistant to activation by CPX. We conclude that, since these antagonists are of relatively low toxicity and appear to act somewhat selectively, they might be considered as promising therapeutic candidates for CF. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 401,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,DEPT BIOL CHEM,JERUSALEM,ISRAEL. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20]; NHLBI NIH HHS [HL-40518] NR 43 TC 84 Z9 84 U1 2 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5562 EP 5566 DI 10.1073/pnas.89.12.5562 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300074 PM 1376923 ER PT J AU HALLENBECK, PL MARKS, MS LIPPOLDT, RE OZATO, K NIKODEM, VM AF HALLENBECK, PL MARKS, MS LIPPOLDT, RE OZATO, K NIKODEM, VM TI HETERODIMERIZATION OF THYROID-HORMONE (TH) RECEPTOR WITH H-2RIIBP (RXR-BETA) ENHANCES DNA-BINDING AND TH-DEPENDENT TRANSCRIPTIONAL ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RESPONSE ELEMENT; NEGATIVE REGULATION; NUCLEAR-PROTEIN; DIMER FORMATION; LEUCINE-ZIPPER; DOMAIN; COMPLEXES; SEQUENCE; GENE; FOS AB Steroid/TH receptors mediate transcriptional induction of promoters containing hormone response elements (HREs) through an unclear mechanism that involves receptor binding to both hormone and a HRE. Here we demonstrate that both HRE binding and the transcriptional inducing activities of one member of this family, TH receptor, were markedly enhanced by heterodimerization with H-2RIIBP, a non-TH-binding member of the steroid hormone receptor superfamily. H-2RIIBP, the mouse homologue of human retinoic acid-related receptor, was shown to form stable heterodimers with the TH receptor either in solution or when bound to a TH response element. The results presented indicate that it might be necessary for the TH receptor or other members of this superfamily to have specific partners for heterodimer formation to elicit maximal hormone-specific gene regulation from particular HREs. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NR 51 TC 88 Z9 90 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5572 EP 5576 DI 10.1073/pnas.89.12.5572 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300076 PM 1608968 ER PT J AU UCHIDA, K STADTMAN, ER AF UCHIDA, K STADTMAN, ER TI SELECTIVE CLEAVAGE OF THIOETHER LINKAGE IN PROTEINS MODIFIED WITH 4-HYDROXYNONENAL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COVALENT MODIFICATION OF PROTEINS; LIPID PEROXIDATION; CYSTEINE RESIDUES; RANEY NICKEL ID LOW-DENSITY LIPOPROTEIN; GLUTAMINE-SYNTHETASE; CATALYZED OXIDATION; LIVER; PEROXIDATION; PRODUCTS; IDENTIFICATION; GLUTATHIONE; ALDEHYDES; MECHANISM AB The peroxidation of polyunsaturated fatty acids leads to numerous products including 4-hydroxynonenal (HNE). That 4-hydroxy-2-alkenal compounds react with sulfhydryl groups of proteins to form thioether adducts possessing a carbonyl function has been established [Schauenstein, E. & Esterbauer, H. (1979) Ciba Found. Symp. 67, 225-244]. Taking advantage of the fact that Raney nickel catalyzes cleavage of thioether bonds, we have developed a procedure to quantitate the amount of HNE moiety bound to protein by means of a thioether linkage. Adducts of HNE with N-acetylcysteine and glutathione were prepared, labeled with NaB[H-3]H-4, and then treated with Raney nickel. The H-3-labeled product was recovered in 85-90% yield from both HNE-N-acetylcysteine and HNE-glutathione adducts in a solvent [10% (vol/vol) methanol/ chloroform]-extractable form. Treatment of proteins with HNE led to the disappearance of protein sulfhydryl groups. However, <10% of the labeled adducts obtained after subsequent reduction with NaB[H-3]H-4 could be released in a solvent-extractable form upon treatment with Raney nickel. This and the observation that HNE reacts with proteins lacking a sulfhydryl group attests to the fact that HNE can react with amino acid residues other than cysteinyl residues. C1 NHLBI,BIOCHEM LAB,9000 ROCKVILLE PIKE,BLDG 3,ROOM 222,BETHESDA,MD 20892. NR 32 TC 131 Z9 134 U1 0 U2 8 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5611 EP 5615 DI 10.1073/pnas.89.12.5611 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300084 PM 1608970 ER PT J AU KWONG, KK BELLIVEAU, JW CHESLER, DA GOLDBERG, IE WEISSKOFF, RM PONCELET, BP KENNEDY, DN HOPPEL, BE COHEN, MS TURNER, R CHENG, HM BRADY, TJ ROSEN, BR AF KWONG, KK BELLIVEAU, JW CHESLER, DA GOLDBERG, IE WEISSKOFF, RM PONCELET, BP KENNEDY, DN HOPPEL, BE COHEN, MS TURNER, R CHENG, HM BRADY, TJ ROSEN, BR TI DYNAMIC MAGNETIC-RESONANCE-IMAGING OF HUMAN BRAIN ACTIVITY DURING PRIMARY SENSORY STIMULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; FUNCTIONAL ARCHITECTURE; INTRINSIC SIGNALS; STRIATE CORTEX; DEPENDENCE; CONTRAST; FIELDS; INVIVO AB Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P < 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (Ml) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. MASSACHUSETTS EYE & EAR INFIRM,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP KWONG, KK (reprint author), MASSACHUSETTS GEN HOSP,CTR MGH NMR,DEPT RADIOL,BOSTON,MA 02114, USA. RI Turner, Robert/C-1820-2008; Kennedy, David/H-3627-2012; Li, Chong/F-4265-2015; Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NCI NIH HHS [5PO1CA48729-02, R01-CA40303]; NHLBI NIH HHS [R01-HL39810] NR 38 TC 2711 Z9 2774 U1 18 U2 169 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 1992 VL 89 IS 12 BP 5675 EP 5679 DI 10.1073/pnas.89.12.5675 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY053 UT WOS:A1992HY05300097 PM 1608978 ER PT J AU ESPELAND, MA BYINGTON, RP HIRE, D DAVIS, VG HARTWELL, T PROBSTFIELD, J AF ESPELAND, MA BYINGTON, RP HIRE, D DAVIS, VG HARTWELL, T PROBSTFIELD, J TI ANALYSIS STRATEGIES FOR SERIAL MULTIVARIATE ULTRASONOGRAPHIC DATA THAT ARE INCOMPLETE SO STATISTICS IN MEDICINE LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; GROWTH-CURVES; EM-ALGORITHM; REGRESSION-ANALYSIS; MAXIMUM-LIKELIHOOD; EFFECTS MODELS; MATRICES; WEIGHTS AB Ultrasonographic measurement of intima-media thicknesses in the carotid artery has emerged as an important non-invasive means of assessing atherosclerosis, and has served to define primary outcome measures related to progression of arterial lesions in several large clinical trials and epidemiologic studies. It is characteristic that measurements often cannot be obtained from all sites during repeated examinations. This leads to incomplete multivariate serial data, for which the set and number of visualized sites may vary across time. We have contrasted several conditional and unconditional maximum likelihood analytical approaches, and have evaluated these with a simulation experiment based on characteristics of ultrasound measurements collected during the course of the Asymptomatic Carotid Artery Plaque Study. We examined analyses based on unweighted and generalized least squares regression in which we estimated cross-sectional summary statistics using raw means, unconditional maximum likelihood estimates and full maximum likelihood estimates. Since the genesis of missing data is not fully clear, and since the approaches we examined are based, to some degree, on the assumption that data are missing at random, we also examined the relative impact of deviations from such an assumption on each of the approaches considered. We found that maximum likelihood based approaches increased the expected efficiency of the analysis of serial ultrasound data over ignoring missing data by up to 21 per cent. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NHLBI,DECA,CLIN TRIALS BRANCH,BETHESDA,MD 20892. RP ESPELAND, MA (reprint author), BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [R01-HL-38194] NR 29 TC 42 Z9 42 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1992 VL 11 IS 8 BP 1041 EP 1056 DI 10.1002/sim.4780110806 PG 16 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 JB429 UT WOS:A1992JB42900005 PM 1496192 ER PT J AU INSEL, TR SHAPIRO, LE AF INSEL, TR SHAPIRO, LE TI OXYTOCIN RECEPTORS AND MATERNAL-BEHAVIOR SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID RAT-BRAIN; PARAVENTRICULAR NUCLEUS; MICROTUS-OCHROGASTER; BINDING-SITES; FEMALE RATS; VAGINOCERVICAL STIMULATION; NEUROHYPOPHYSEAL PEPTIDES; AFFILIATIVE BEHAVIOR; CEREBROSPINAL-FLUID; ESTROGEN-TREATMENT RP INSEL, TR (reprint author), NIMH,CLIN SCI LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 74 TC 41 Z9 41 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 12 PY 1992 VL 652 BP 122 EP 141 DI 10.1111/j.1749-6632.1992.tb34350.x PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM567 UT WOS:A1992JM56700010 PM 1320825 ER PT J AU CARTER, CS WILLIAMS, JR WITT, DM INSEL, TR AF CARTER, CS WILLIAMS, JR WITT, DM INSEL, TR TI OXYTOCIN AND SOCIAL BONDING SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID VOLES MICROTUS-OCHROGASTER; PRAIRIE VOLES; SEXUAL-BEHAVIOR; MATING SYSTEM; FEMALE RATS; RELEASE; MEMORY C1 NIMH,CLIN SCI LAB,POOLESVILLE,MD 20837. RP CARTER, CS (reprint author), UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742, USA. NR 44 TC 127 Z9 128 U1 4 U2 24 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 12 PY 1992 VL 652 BP 204 EP 211 DI 10.1111/j.1749-6632.1992.tb34356.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM567 UT WOS:A1992JM56700016 PM 1626829 ER PT J AU WITT, DM INSEL, TR AF WITT, DM INSEL, TR TI CENTRAL OXYTOCIN ANTAGONISM DECREASES FEMALE REPRODUCTIVE-BEHAVIOR SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID LORDOSIS BEHAVIOR; RATS; FACILITATION; RECEPTORS RP WITT, DM (reprint author), NIMH,CLIN SCI LAB,POOLESVILLE,MD 20837, USA. NR 7 TC 11 Z9 11 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 12 PY 1992 VL 652 BP 445 EP 447 DI 10.1111/j.1749-6632.1992.tb34379.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM567 UT WOS:A1992JM56700039 PM 1320836 ER PT J AU SHAPIRO, LE INSEL, TR AF SHAPIRO, LE INSEL, TR TI OXYTOCIN RECEPTOR DISTRIBUTION REFLECTS SOCIAL-ORGANIZATION IN MONOGAMOUS AND POLYGAMOUS VOLES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article RP SHAPIRO, LE (reprint author), NIMH,CLIN SCI LAB,POOLESVILLE,MD 20837, USA. NR 5 TC 13 Z9 13 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 12 PY 1992 VL 652 BP 448 EP 451 DI 10.1111/j.1749-6632.1992.tb34380.x PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM567 UT WOS:A1992JM56700040 PM 1320837 ER PT J AU WINSLOW, JT INSEL, TR AF WINSLOW, JT INSEL, TR TI SOCIAL AND ENVIRONMENTAL DETERMINANTS OF CENTRALLY ADMINISTERED OXYTOCIN EFFECTS ON MALE SQUIRREL-MONKEY BEHAVIOR SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FEMALE RATS; RECEPTORS; BRAIN RP WINSLOW, JT (reprint author), NIMH,HIHAC,CLIN SCI LAB,POOLESVILLE,MD 20837, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 12 PY 1992 VL 652 BP 452 EP 455 DI 10.1111/j.1749-6632.1992.tb34381.x PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM567 UT WOS:A1992JM56700041 PM 1626846 ER PT J AU WILLIAMS, JR CARTER, CS INSEL, T AF WILLIAMS, JR CARTER, CS INSEL, T TI PARTNER PREFERENCE DEVELOPMENT IN FEMALE PRAIRIE VOLES IS FACILITATED BY MATING OR THE CENTRAL INFUSION OF OXYTOCIN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NIMH,CLIN SCI LAB,POOLESVILLE,MD 20847. RP WILLIAMS, JR (reprint author), UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742, USA. NR 4 TC 67 Z9 68 U1 1 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 12 PY 1992 VL 652 BP 487 EP 489 DI 10.1111/j.1749-6632.1992.tb34393.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM567 UT WOS:A1992JM56700053 PM 1626857 ER PT J AU SIDDIQUI, MA DRISCOLL, JS MARQUEZ, VE ROTH, JS SHIRASAKA, T MITSUYA, H BARCHI, JJ KELLEY, JA AF SIDDIQUI, MA DRISCOLL, JS MARQUEZ, VE ROTH, JS SHIRASAKA, T MITSUYA, H BARCHI, JJ KELLEY, JA TI CHEMISTRY AND ANTI-HIV PROPERTIES OF 2'-FLUORO-2',3'-DIDEOXYARABINOFURANOSYLPYRIMIDINES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIVIRAL ACTIVITY; NUCLEOSIDE ANALOGS; III INFECTIVITY; 2',3'-DIDEOXYCYTIDINE; INVITRO; REPLICATION; METABOLISM; INHIBITION; TOXICITY; AGENTS AB The synthesis, chemistry, biochemistry, and anti-HIV activity of a series of 1-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)pyrimidines have been studied in an attempt to find useful anti-AIDS drugs. Synthesis is carried out via a 2,3-dideoxyribose intermediate which facilitates the preparation of analogues by removing the sugar 3'-hydroxyl group prior to, rather than after, condensation with a uracil or cytosine aglycon. The 2'-F-dd-uridine analogues 7a-d (with H, F, Cl, and CH3 substitution in the 5-position) as well as the 4-deoxy compound (12b) are nonprotective to ATH8 or CEM cells infected with HIV-1. In the corresponding cytidine series, the 5-chloro analogue (11) is inactive. However, 2'-fluoro-2',3'-dideoxyarabinosylcytosine, 10a, and its 5-fluoro analogue, 10b, are both active. While neither compound is as potent as ddC or 5-F-ddC (2b), 10b gives complete protection against the cytopathic effects of HIV in both host cell lines. 2-Fluoro substitution confers increased chemical and enzymatic stability on dideoxynucleosides. Even though dideoxy pyrimidine nucleosides are inherently more stable than the corresponding purine analogues toward acid-catalyzed cleavage of the glycosidic bond, 2'-fluoro substitution (10a) still increases stabilization relative to ddC (2b). No detectable deamination by partially purified cytidine deaminase is observed with the 2'-fluoro compounds 10a, 10b, or 11 under conditions which rapidly deaminate cytidine. A small amount of 2'-F-dd-ara-U (7a) is formed from 10a in monkey plasma after >24 h of exposure. The octanol-water partition coefficients for the dideoxynucleosides in this study indicate their hydrophilic character, with log P values varying from -0.28 to -1.18. C1 NCI,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,MED BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NR 35 TC 18 Z9 18 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 12 PY 1992 VL 35 IS 12 BP 2195 EP 2201 DI 10.1021/jm00090a008 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA HZ303 UT WOS:A1992HZ30300008 PM 1351945 ER PT J AU DECOSTA, B RADESCA, L DOMINGUEZ, C DIPAOLO, L BOWEN, WD AF DECOSTA, B RADESCA, L DOMINGUEZ, C DIPAOLO, L BOWEN, WD TI SYNTHESIS AND RECEPTOR-BINDING PROPERTIES OF FLUORO-SUBSTITUTED AND IODO-SUBSTITUTED HIGH-AFFINITY SIGMA-RECEPTOR LIGANDS - IDENTIFICATION OF POTENTIAL PET AND SPECT SIGMA-RECEPTOR IMAGING AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN; BENZODIAZEPINE RECEPTORS; VAS-DEFERENS; SITE; INHIBITION; F-18 AB Unlabeled fluoro- and iodo-substituted ligands exhibiting very high affinity and selectivity for sigma-receptors were synthesized based on three different structural classes of sigma-receptor ligands. These compounds were evaluated for sigma-receptor affinity and specificity in order to assess their potential as PET/SPECT imaging agents. Thus, (+)- and (-)-N-(5-fluoro-1-pentyl)normetazocines [(+)- and (-)-41 based on the (+)-benzomorphan class of sigma-ligands were synthesized via N-alkylation of optically pure (+)- and (-)-normetazocine with 5-[(methylsulfonyl)oxyl-l-pentyl fluoride (11). (+)- and (-)-4 displaced [H-3](+)-3-PPP with K(i) values of 0.29 and 73.6 nM and [H-3](+)-pentazocine with K(i) values of 10.5 and 38.9 nM, respectively. The second class of PET/SPECT ligands was based upon the N-(arylethyl)-N-alkyl-2-(1-pyrrolidinyl)ethylamine class of sigma-ligands; N-[2-(3,4-dichlorophenyl)-l-ethyl]-N-(3-fluoro-1-propyl)-2-(1-pyrrolidinyl)ethylamine (5) was obtained via N-alkylation of N-[2-(3,4-dichlorophenyl)-l-ethyl]-2-(1-pyrrolidinyl)ethylamine (14) with 3-fluoropropyl p-toluenesulfonate. 5 exhibited K(i) values of 4.22 and 5.07 nM for displacement of [H-3] (+)-3-PPP and [H-3] (+)-pentazocine, respectively, comparable with the parent N-propyl compound. Attempts to synthesize N-[2-(3,4-dichlorophenyl)-1-ethyl]-N-[3-[(methylsulfonyl)oxy]-1-propyl]-2-(1-pyrrolidinyl)ethylamine (26), a precursor to 5 that could conceivably be converted to [F-18]-5 by treatment with F-18, proved unsuccessful. The sequence of regioselective nitration, catalytic hydrogenation, and diazotization followed by NaI quench of N-[2-(3,dichlorophenyl)-1-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) afforded the iodinated ethylenediamine N-[2-(2-iodo-4,5-dichlorophenyl)-1-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (8), a potential SPECT ligand for sigma-receptors. This compound showed an affinity of 0.54 nM ([H-3](+)-3-PPP) comparable with the parent compound 2 (K(i) = 0.34 nM, [H-3](+)-3-PPP). Ligand 8 exhibited a similar potency against [H-3](+)-pentazocine. The third class of high-affinity sigma-receptor ligands was rationalized based on rearrangement of the bonds in ethylenediamine 2 to give 1-[2-(3,4-dichlorophenyl)-l-ethyl]-4-(1-propyl)piperazine (3). This compound exhibited very high affinity (K(i) = 0.31 nM, [H-3](+)-3-PPP) and selectivity for sigma-receptors. Compound 3 was synthesized in three steps from commercially available 1-propylpiperazine and served as a template for the synthesis of PET and SPECT compounds 1-[3-fluoro-(1-propyl)]4[2-(3,4-dichlorophenyl)ethyl]piperazine (6) (K(i) = 4.24 nM, [H-3](+)-3-PPP), 1-(5-fluoro-1-pentyl)-4-[2-(3,4-dichlorophenyl)ethyl]piperazine (7) (K(i) = 0.86 nM, [H-3](+)-3-PPP), and 1-(3-iodo-1-propyl)-4- [2-(3,4-dichlorophenyl)ethyl]piperazine (9) (K(i) = 1.32 nM, [H-3] (+)-3-PPP). Compound 7 was synthesized via N-alkylation of 1-(3,4-dichlorophenylacetyl)piperazine (19) with 11, followed by AlH3 reduction. Ligands 6 and 9 were obtained via reaction between 1-[3-[(methylsulfonyl)oxy]-1-propyl]-4-[2-(3,4-dichlorophenyl)ethyl]piperazine (22) and the corresponding anions F- (in acetonitrile) and I- (in acetone). The ease of generation of 6 and 9 from methanesulfonate ester 22 and of 8 from the corresponding aniline 29 combined with their very high affinity identifies them as potentially useful PET/SPECT ligands. All compounds 4-9 displayed very high a receptor affinity and showed low to negligible affinity for several receptor systems which commonly cross-react with sigma-ligands (kappa, phencyclidine, D2-dopamine, and muscarinic/cholinergic). In general, it appeared that the K(i) values for displacement of [H-3](+)-3-PPP correlated with those obtained for displacement of [H-3](+)-pentazocine, suggesting that these compounds interact with the same population of sigma-receptors. However, exceptions observed with (+)-4 and 6 suggest a more complex interaction with a sites. C1 BROWN UNIV,DEPT BIOL & MED,BIOCHEM SECT,PROVIDENCE,RI 02912. RP DECOSTA, B (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [DA04988]; NINDS NIH HHS [NS26746] NR 46 TC 20 Z9 20 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 12 PY 1992 VL 35 IS 12 BP 2221 EP 2230 DI 10.1021/jm00090a012 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA HZ303 UT WOS:A1992HZ30300012 PM 1319493 ER PT J AU CUSHMAN, M NAGARATHNAM, D GOPAL, D HE, HM LIN, CM HAMEL, E AF CUSHMAN, M NAGARATHNAM, D GOPAL, D HE, HM LIN, CM HAMEL, E TI SYNTHESIS AND EVALUATION OF ANALOGS OF (Z)-1-(4-METHOXYPHENYL)-2-(3,4,5-TRIMETHOXYPHENYL)ETHENE AS POTENTIAL CYTOTOXIC AND ANTIMITOTIC AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID INHIBIT TUBULIN POLYMERIZATION; ANTITUBULIN ACTIVITY; CELL-LINES; PODOPHYLLOTOXIN; THIOCOLCHICINE; COLCHICINE; CONGENERS; COMBRETASTATIN-A4; DERIVATIVES; STEGANACIN AB A series of stilbenes has been prepared and tested for cytotoxicity in the five human cancer cell lines A-549 non-small cell lung, MCF-7 breast, HT-29 colon, SKMEL-5 melanoma, and MLM melanoma. The cis stilbenes 6a-f proved to be cytotoxic in all five cell lines, with potencies comparable to that of combretastatin A-4. These cytotoxic compounds were all potent inhibitors of tubulin polymerization. The corresponding trans stilbenes 7b-f were inactive as tubulin polymerization inhibitors and were significantly less cytotoxic in the five cancer cell lines. In the dihydro series, 8b, 8c, and 8f were inactive as tubulin polymerization inhibitors, while 8a, 8d, and 8e were less active than the corresponding cis compounds 6a, 6d, and 6e. The lack of tubulin polymerization inhibitory activity and cytotoxicity displayed by the phenanthrene 23b, which was synthesized as a conformationally rigid analogue of the lead compound 1, indicates that the activity of the stilbenes is not due to a totally planar conformation. Similarly, inactivity of the conformationally restricted analogue 26 suggests that the biologically active conformation of 1a resembles that of the cis alkene 1. Additional inactive compounds prepared include the benzylisoquinoline series 28-32 as well as the protoberberines 38 and 39. Shortening the two-carbon bridge of la to a one-carbon bridge in the diphenylmethane 20 resulted in a decrease in cytotoxicity and tubulin polymerization inhibitory activity. Although the corresponding benzophenone 18 was as active as 1a as a tubulin polymerization inhibitor, it was less cytotoxic than 1a, and the benzhydrol 19 was essentially inactive. With the exception of the amide 15c, which displayed low antitubulin activity, all of the phenylcinnamic acid derivatives 14a-c and 15a-f were inactive in the tubulin polymerization inhibition assay. The acid 14b and the ester 15a were cytotoxic in several of the cancer cell cultures in spite of their inactivity as tubulin polymerization inhibitors. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP CUSHMAN, M (reprint author), PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907, USA. FU NCI NIH HHS [CA47476, N01-CM-17512] NR 42 TC 195 Z9 198 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 12 PY 1992 VL 35 IS 12 BP 2293 EP 2306 DI 10.1021/jm00090a021 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA HZ303 UT WOS:A1992HZ30300021 PM 1613753 ER PT J AU CULVER, KW RAM, Z WALLBRIDGE, S ISHII, H OLDFIELD, EH BLAESE, RM AF CULVER, KW RAM, Z WALLBRIDGE, S ISHII, H OLDFIELD, EH BLAESE, RM TI INVIVO GENE-TRANSFER WITH RETROVIRAL VECTOR PRODUCER CELLS FOR TREATMENT OF EXPERIMENTAL BRAIN-TUMORS SO SCIENCE LA English DT Article ID THYMIDINE KINASE GENES; RAT-BRAIN; INTERLEUKIN-2; POTENT AB Direct in situ introduction of exogenous genes into proliferating tumors could provide an effective therapeutic approach for treatment of localized tumors. Rats with a cerebral glioma were given an intratumoral stereotaxic injection of murine fibroblasts that were producing a retroviral vector in which the herpes simplex thymidine kinase (HS-tk) gene had been inserted. After 5 days during which the HS-tk retroviral vectors that were produced in situ transduced the neighboring proliferating glioma cells, the rats were treated with the anti-herpes drug ganciclovir. Gliomas in the ganciclovir- and vector-treated rats regressed completely both macroscopically and microscopically. This technique exploits what was previously considered to be a disadvantage of retroviral vectors-that is, their inability to transfer genes into nondividing cells. Instead, this feature of retroviruses is used to target gene delivery to dividing tumor cells and to spare nondividing neural tissue. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP CULVER, KW (reprint author), NCI,METAB BRANCH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 17 TC 1436 Z9 1466 U1 3 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 JUN 12 PY 1992 VL 256 IS 5063 BP 1550 EP 1552 DI 10.1126/science.1317968 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HY075 UT WOS:A1992HY07500027 PM 1317968 ER PT J AU MOFENSON, LM SHEARER, WT MOYE, J NUGENT, R WILLOUGHBY, A AF MOFENSON, LM SHEARER, WT MOYE, J NUGENT, R WILLOUGHBY, A TI MANIPULATING THE IMMUNE-SYSTEM WITH IMMUNE GLOBULIN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MOFENSON, LM (reprint author), NIH,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 11 PY 1992 VL 326 IS 24 BP 1636 EP 1637 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HX633 UT WOS:A1992HX63300024 PM 1584276 ER PT J AU GANT, TW SILVERMAN, JA THORGEIRSSON, SS AF GANT, TW SILVERMAN, JA THORGEIRSSON, SS TI REGULATION OF P-GLYCOPROTEIN GENE-EXPRESSION IN HEPATOCYTE CULTURES AND LIVER-CELL LINES BY A TRANS-ACTING TRANSCRIPTIONAL REPRESSOR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MULTIDRUG-RESISTANT CELLS; HAMSTER OVARY CELLS; PROTEIN-SYNTHESIS; MESSENGER-RNA; GROWTH-FACTOR; C-MYC; AMPLIFICATION; RAT; OVEREXPRESSION; INDUCTION AB Previously we have demonstrated that expression of the multidrug resistance (mdr) genes in rat liver and primary rat hepatocyte cultures is induced by exposure to 2-acetylaminofluorene and 3-methylcholanthrene. The mdr expression induced by both of these compounds occurs primarily via increased gene transcription. To determine the nature of possible regulatory proteins involved in mdr gene regulation we inhibited protein synthesis using cycloheximide or emetine in primary rat hepatocyte cultures, mouse (HePa 1), human (Hep G2) and rat (H4-II-E) cell lines. Each cell type responded by strongly increasing its steady state mdr1 mRNA levels. In hepatocytes increased mdr expression was observed after greater than 50% inhibition of protein synthesis, and was first detected after 2h of protein synthesis inhibition with maximal induction occurring by 24h. Nuclear run-on analysis showed that the increased steady state mRNA level was due to increased gene transcription without alteration of the transcription start site. Combined these data indicate that one regulatory mechanism by which mdr gene expression is controlled is via a trans-acting transcriptional repressor. RP GANT, TW (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 56 TC 64 Z9 64 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1992 VL 20 IS 11 BP 2841 EP 2846 DI 10.1093/nar/20.11.2841 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ673 UT WOS:A1992HZ67300030 PM 1352042 ER PT J AU LANDSMAN, D AF LANDSMAN, D TI RNP-1, AN RNA-BINDING MOTIF IS CONSERVED IN THE DNA-BINDING COLD SHOCK DOMAIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN; MESSENGER-RNA; Y-BOX; PROTEINS; GENE; DROSOPHILA; SEQUENCE; SEX; CONSENSUS AB Sequence analysis has shown that there is a short motif of 8 amino acids, corresponding to the RNP-1 motif found in canonical RNA-binding domains, which is common to two families of apparently unrelated proteins. Many RNA-binding proteins contain the RNP-1 and RNP-2 motifs in an RNA-binding domain. The cold shock domain (CSD) family of proteins, which includes several transcription factors which have been shown to bind to DNA, has now been identified to contain a motif similar to RNP-1. A non-redundant protein sequence database was searched with regular expressions and with a weight/residue position matrix of the RNP-1 motif resulting in the identification of numerous known members of the RNA-binding family of proteins. In addition, the search identified that the CSD-containing family of proteins includes a motif which is almost identical to the RNP-1 motif. A determination of the statistical significance of this analysis showed that the RNP-1 motifs from these two families of proteins are indeed similar. RP LANDSMAN, D (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N-807,BETHESDA,MD 20892, USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 27 TC 106 Z9 106 U1 3 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1992 VL 20 IS 11 BP 2861 EP 2864 DI 10.1093/nar/20.11.2861 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ673 UT WOS:A1992HZ67300033 PM 1614871 ER PT J AU TAYLOR, JA LI, Y YOU, M WILCOX, AJ LIU, E AF TAYLOR, JA LI, Y YOU, M WILCOX, AJ LIU, E TI B-REGION VARIANT OF THE ESTROGEN-RECEPTOR GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27514. MED COLL OHIO,TOLEDO,OH 43699. RP TAYLOR, JA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27516, USA. RI Liu, Edison/C-4141-2008; OI Wilcox, Allen/0000-0002-3376-1311; taylor, jack/0000-0001-5303-6398 NR 2 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 11 PY 1992 VL 20 IS 11 BP 2895 EP 2895 DI 10.1093/nar/20.11.2895 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HZ673 UT WOS:A1992HZ67300047 PM 1614882 ER PT J AU CHOW, WH DEVESA, SS AF CHOW, WH DEVESA, SS TI DEATH CERTIFICATE REPORTING OF COLON AND RECTAL CANCERS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP CHOW, WH (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 10 PY 1992 VL 267 IS 22 BP 3028 EP 3028 DI 10.1001/jama.267.22.3028 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HW970 UT WOS:A1992HW97000014 PM 1588710 ER PT J AU BRUZIK, KS MOROCHO, AM JHON, DY RHEE, SG TSAI, MD AF BRUZIK, KS MOROCHO, AM JHON, DY RHEE, SG TSAI, MD TI PHOSPHOLIPIDS CHIRAL AT PHOSPHORUS - STEREOCHEMICAL MECHANISM FOR THE FORMATION OF INOSITOL 1-PHOSPHATE CATALYZED BY PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE-C SO BIOCHEMISTRY LA English DT Article ID MYOINOSITOL 1-2-CYCLIC PHOSPHATE; BACILLUS-CEREUS; GLYCOSYL-PHOSPHATIDYLINOSITOL; 2ND MESSENGERS; P-31 NMR; STEREOSPECIFICITY; PURIFICATION; CLEAVAGE; O-18 AB The phosphatidylinositol-specific phospholipase C (PI-PLC) from mammalian sources catalyzes the simultaneous formation of both inositol 1,2-cyclic phosphate (IcP) and inositol 1-phosphate (IP). It has not been established whether the two products are formed in sequential or parallel reactions, even though the latter has been favored in previous reports. This problem was investigated by using a stereochemical approach. Diastereomers of 1,2-dipalmitoyl-sn-glycero-3-(1D-[O-16, O-17]phosphoinositol) ([O-16, O-17]DPPI) and 1,2-dipalmitoyl-sn-glycero-3-(1D-thiophosphoinositol) (DPPsI) were synthesized, the latter with known configuration. Desulfurization of the DPPsI isomers of known configurations in (H2O)-O-18 gave [O-16, O-18]DPPI with known configurations, which allowed assignment of the configurations of [O-16, O-17]DPPI on the basis of P-31 NMR analyses of silylated [O-16, O-18] DPPI and [O-16, O-18] DPPI (the inositol moiety was fully protected in this operation). (R(p))- and (S(p))-[O-16, O-17]DPPI were then converted into trans- and CiS-[O-16, O-17]Icp, respectively, by PI-PLC from Bacillus cereus, which had been shown to proceed with inversion of configuration at phosphorus [Lin, G., Bennett, F. C., & Tsai, M.-D. (1990) Biochemistry 29, 2747-2757]. P-31 NMR analysis was again used to differentiate the silylated products of the two isomers of IcP, which then permitted assignments of IcP with unknown configuration derived from transesterification of (R(p))- and (S(p))-[O-16, O-17]DPPI by bovine brain PI-PLC-beta-1. The results indicated inversion of configuration, in agreement with the steric course of the same reaction catalyzed by PI-PLCs from B. cereus and guinea pig uterus reported previously. For the steric course of the formation of inositol 1-phosphate catalyzed by PI-PLC, (R(p))- and (S(p))-[O-16, O-17]DPPI were hydrolyzed in (H2O)-O-18 to afford 1-[O-16, O-17, O-18]IP, which was then converted to IcP chemically and analyzed by P-31 NMR. The results indicated that both B. cereus PI-PLC and the PI-PLC-beta-1 from bovine brain catalyze conversion of DPPI to IP with overall retention of configuration at phosphorus. These results suggest that both bacterial and mammalian PI-PLCs catalyze the formation of IcP and IP by a sequential mechanism. However, the conversion of IcP to IP was detectable by P-31 NMR only for the bacterial enzyme. Thus an alternative mechanism in which IcP and IP are formed by totally independent pathways, with formation of IP involving a covalent enzyme-phosphoinositol intermediate, cannot be ruled out for the mammalian enzyme. It was also found that both PI-PLCs displayed lack of stereospecifically toward the 1,2-diacylglycerol moiety, which suggests that the hydrophobic part of phosphatidylinositol is not recognized by PI-PLC. C1 NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA. RP OHIO STATE UNIV, DEPT CHEM, COLUMBUS, OH 43210 USA. FU NCRR NIH HHS [RR 01458]; NIGMS NIH HHS [GM 30327] NR 43 TC 57 Z9 57 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 9 PY 1992 VL 31 IS 22 BP 5183 EP 5193 DI 10.1021/bi00137a014 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX912 UT WOS:A1992HX91200014 PM 1318746 ER PT J AU GRIFFITHS, JT PHYLIP, LH KONVALINKA, J STROP, P GUSTCHINA, A WLODAWER, A DAVENPORT, RJ BRIGGS, R DUNN, BM KAY, J AF GRIFFITHS, JT PHYLIP, LH KONVALINKA, J STROP, P GUSTCHINA, A WLODAWER, A DAVENPORT, RJ BRIGGS, R DUNN, BM KAY, J TI DIFFERENT REQUIREMENTS FOR PRODUCTIVE INTERACTION BETWEEN THE ACTIVE-SITE OF HIV-1 PROTEINASE AND SUBSTRATES CONTAINING -HYDROPHOBIC-ASTERISK HYDROPHOBIC- OR -AROMATIC-ASTERISK PRO- CLEAVAGE SITES SO BIOCHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS-1; CRYSTAL-STRUCTURE; PROTEASE; INHIBITOR; COMPLEX; RESOLUTION; DESIGN AB The sequence requirements for HIV-1 proteinase catalyzed cleavage of oligopeptides containing two distinct types of junctions (-hydrophobic*hydrophobic- or -aromatic*Pro-) has been investigated. For the first type of junction (-hydrophobic*hydrophobic-) the optimal residues in the P2 and P2' positions were found to be Val and Glu, respectively, in accord with recent statistical analysis of natural cleavage sites [Poorman, R. A., Tomasselli, A. G., Heinrikson, R. L., & Kezdy, F. J. (1991) J. Biol. Chem. 266, 14554-14561]. For the -aromatic*Pro- type of junction, in the specific sequence context studied here, the value of Glu in the P2' position was again observed. An explanation for the inefficient cleavage observed for peptides with the sequence -Val-Tyr*Pro- has been provided from molecular modeling of the putative enzyme-substrate complex. A significant effect upon cleavage rates due to the amino acid in the P5 position has also been documented. While lysine in the P5 position in one sequence of the -hydrophobic*hydrophobic-type produces a peptide cleaved very efficiently (k(cat) > 15 s-1 for Lys-Ala-Arg-Val-Nle*p-nitrophenyl-alanine-P2'-Ala-Nle-NH2, for P2' = Glu, Gln, Ile, Val, or Ala), for substrates of the -aromatic*Pro- type, the P5 residue can exert either a positive or negative effect on cleavage rates. These results have again been interpreted in light of molecular modeling. We suggest that interaction of the substrate sequence on the periphery of the active site cleft may influence the match of the enzyme-substrate pair and, hence, control the efficiency of catalysis. Thus, ability of HIV-1 PR to selectively and efficiently cleave a variety of totally different sequences may be derived, in part, from extensive interactions at long distances from the actual scissile peptide bond and the inherent flexibility of several key loops of polypeptide structure of the enzyme. C1 UNIV FLORIDA, DEPT BIOCHEM & MOLEC BIOL, BOX 100245, GAINESVILLE, FL 32610 USA. UNIV WALES COLL CARDIFF, DEPT BIOCHEM, CARDIFF CF1 1ST, WALES. CZECHOSLOVAK ACAD SCI, INST ORGAN CHEM & BIOCHEM, CS-16610 PRAGUE 6, CZECHOSLOVAKIA. NCI, FREDERICK CANC RES & DEV CTR, MACROMOLEC STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Konvalinka, Jan/G-7518-2014 FU NCI NIH HHS [N01-CO74101]; NIAID NIH HHS [AI28571] NR 34 TC 92 Z9 93 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 9 PY 1992 VL 31 IS 22 BP 5193 EP 5200 DI 10.1021/bi00137a015 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX912 UT WOS:A1992HX91200015 PM 1606143 ER PT J AU PELTON, JG TORCHIA, DA MEADOW, ND ROSEMAN, S AF PELTON, JG TORCHIA, DA MEADOW, ND ROSEMAN, S TI STRUCTURAL COMPARISON OF PHOSPHORYLATED AND UNPHOSPHORYLATED FORMS OF III(GLC), A SIGNAL-TRANSDUCING PROTEIN FROM ESCHERICHIA-COLI, USING 3-DIMENSIONAL NMR TECHNIQUES SO BIOCHEMISTRY LA English DT Article ID BACTERIAL PHOSPHOTRANSFERASE SYSTEM; HISTIDINE-CONTAINING PROTEIN; NUCLEAR MAGNETIC-RESONANCE; TWO-DIMENSIONAL NMR; PHOSPHOCARRIER PROTEIN; SUGAR-TRANSPORT; SALMONELLA-TYPHIMURIUM; STAPHYLOCOCCUS-AUREUS; TERTIARY STRUCTURE; BACILLUS-SUBTILIS AB The 18.1-kDa protein III(Glc) from Escherichia coli acts as both a phosphocarrier protein in the phosphoenolpyruvate:glycose phosphotransferase system (PTS) and as a signal-transducing protein with respect to the uptake of non-PTS sugars. Phosphorylation of III(Glc) at the N(epsilon) (N3) position of His-90 was effected through a regeneration system that included MgCl2, DTT, excess PEP, and catalytic amounts of Enzyme I and HPr. NH, N-15, and C-13-alpha signal assignments for P-III(Glc) were made through comparison of N-15-H-1 correlation spectra (HSQC) of uniformly N-15-labeled preparations of phosphorylated and unphosphorylated protein and through analysis of three-dimensional triple-resonance HNCA spectra of P-III(Glc) uniformly labeled with both N-15 and C-13. Backbone and side-chain H-1 and C-13-beta signals were assigned using 3D heteronuclear HCCH-COSY and HCCH-TOCSY spectra of P-III(Glc). Using this approach, the assignments were made without reference to nuclear Overhauser effect data or assumptions regarding protein structure. The majority of NH, N-15, H-alpha, and C-13-alpha chemical shifts measured for P-III(Glc) were identical to those obtained for the unphosphorylated protein [Pelton, J. G., Torchia, D. A., Meadow, N. D., Wong C.-Y., & Roseman, S. (1991) Biochemistry 30, 100431. Those signals that exhibited shifts corresponded to residues within four segments (1) Leu-87-Gly-100, (2) Val-36-Val-46, (3) His-75-Ser-78, and (4) Ala-131-Val-138. These four segments are in close proximity to the active site residues His-75 and His-90 in the unphosphorylated protein [Worthylake, D., Meadow, N. D., Roseman, S., Liao, D., Hertzberg, O., & Remington, S. J. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 10382], and the chemical shift data provide strong evidence that if any structural changes accompany phosphorylation, they are confined to residues in these four segments. This conclusion is confirmed by comparing NOEs observed in 3D N-15/C-13 NOESY-HMQC spectra of the two forms of the protein. No NOE differences are seen for residues having the same chemical shifts in III(GlC) and P-III(Glc). Furthermore, with the exception of residues Ala-76, Asp-94, and Val-96, the NOEs of residues (in the four segments) which exhibited chemical shift differences also had the same NOEs in III(Glc) and P-III(Glc). In the case of residues Ala-76, Asp-94, and Val-96, minor differences in NOEs, corresponding to interproton distances changes of less than 1.5 angstrom, were observed. Together, the data show that no large structural rearrangements occur in III(Glc) upon phosphorylation and that the minor structural changes (< 1.5 angstrom) seen are limited to the active site. Hence, the results of structural studies of III(Glc) may be appropriate to modeling studies of the interaction of P-III(Glc) with HPr and other PTS and non-PTS proteins. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,MCCOLLUM PRATT INST,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. FU NIGMS NIH HHS [GM 38759] NR 59 TC 34 Z9 35 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 JUN 9 PY 1992 VL 31 IS 22 BP 5215 EP 5224 DI 10.1021/bi00137a017 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX912 UT WOS:A1992HX91200017 PM 1606145 ER PT J AU ZAJC, B LAKSHMAN, MK SAYER, JM JERINA, DM AF ZAJC, B LAKSHMAN, MK SAYER, JM JERINA, DM TI EPOXIDE AND DIOL EPOXIDE ADDUCTS OF POLYCYCLIC AROMATIC-HYDROCARBONS AT THE EXOCYCLIC AMINO GROUP OF DEOXYGUANOSINE SO TETRAHEDRON LETTERS LA English DT Article DE POLYCYCLIC HYDROCARBONS; DIOL EPOXIDE; 2'-DEOXYGUANOSINE ADDUCTS ID DNA ADDUCTS AB Synthesis and separation of the diastereomeric trans N2-2'-deoxyguanosine adducts of tetrahydrophenanthrene 3,4-epoxide and benzo[a]pyrene 7,8-diol 9, 10-epoxide (benzylic hydroxyl group and epoxide oxygen trans), as well as the incorporation of the former into the pentanucleotide TpApG*pApT, are described. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 16 TC 44 Z9 44 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 9 PY 1992 VL 33 IS 24 BP 3409 EP 3412 DI 10.1016/S0040-4039(00)92649-2 PG 4 WC Chemistry, Organic SC Chemistry GA HY607 UT WOS:A1992HY60700003 ER PT J AU SZALLASI, A BLUMBERG, PM AF SZALLASI, A BLUMBERG, PM TI VANILLOID RECEPTOR LOSS IN RAT SENSORY GANGLIA ASSOCIATED WITH LONG-TERM DESENSITIZATION TO RESINIFERATOXIN SO NEUROSCIENCE LETTERS LA English DT Article DE VANILLOID RECEPTOR; RESINIFERATOXIN; SENSORY GANGLION; RAT ID ULTRAPOTENT CAPSAICIN ANALOG; PHARMACOLOGY AB A dose-dependent loss of vanilloid receptors (specific [H-3]resiniferatoxin binding sites) was found in sensory ganglia of rats 24 h after s.c. administration of resiniferatoxin (RTX), an ultrapotent capsaicin analog. This receptor loss displayed an ED50 of 30-mu-g/kg both in dorsal root and trigeminal ganglia; the ED50 was 6-fold higher than the ED50 for loss of the neurogenic inflammatory response and 30-60-fold higher than the ED50 for desensitization in the standard eye-wiping (chemogenic pain) response. The receptor loss appeared later (24 h) than the loss of the physiological responses (6 h) and showed modest recovery (to 20-30% of control levels) over the following 4 weeks. This vanilloid receptor loss may represent a novel, specific mechanism for vanilloid-induced chronic desensitization. C1 NCI,CELLULAR CARCINOGENESIS LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 18 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 8 PY 1992 VL 140 IS 1 BP 51 EP 54 DI 10.1016/0304-3940(92)90679-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA HZ798 UT WOS:A1992HZ79800013 PM 1407700 ER PT J AU THOMPSON, AM BLUNT, JW MUNRO, MHG PERRY, NB PANNELL, LK AF THOMPSON, AM BLUNT, JW MUNRO, MHG PERRY, NB PANNELL, LK TI CHEMISTRY OF THE MYCALAMIDES, ANTIVIRAL AND ANTITUMOR COMPOUNDS FROM A MARINE SPONGE .3. ACYL, ALKYL AND SILYL DERIVATIVES SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID NEW-ZEALAND SPONGE; ONNAMIDE; MYCALE AB Acyl, alkyl and silyl derivatives of the hydroxy and N-amido functionalities of the antitumour and antiviral marine sponge metabolites mycalamides A and B have been prepared, their relative reactivities established and in vitro P388 leukemia bioassays performed. C1 UNIV CANTERBURY,DEPT CHEM,CHRISTCHURCH 1,NEW ZEALAND. NIDDKD,BETHESDA,MD 20892. RI Perry, Nigel/G-5574-2010 OI Perry, Nigel/0000-0003-3196-3945 NR 17 TC 35 Z9 35 U1 1 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD JUN 7 PY 1992 IS 11 BP 1335 EP 1342 DI 10.1039/p19920001335 PG 8 WC Chemistry, Organic SC Chemistry GA HX970 UT WOS:A1992HX97000011 ER PT J AU PASCUALLEONE, A HOUSER, CM GRAFMAN, J HALLETT, M AF PASCUALLEONE, A HOUSER, CM GRAFMAN, J HALLETT, M TI REACTION-TIME AND TRANSCRANIAL MAGNETIC STIMULATION SO LANCET LA English DT Letter RP PASCUALLEONE, A (reprint author), NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 7 Z9 7 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 6 PY 1992 VL 339 IS 8806 BP 1420 EP 1420 DI 10.1016/0140-6736(92)91245-4 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HX636 UT WOS:A1992HX63600047 PM 1350834 ER PT J AU GIVENS, BS OLTON, DS CRAWLEY, JN AF GIVENS, BS OLTON, DS CRAWLEY, JN TI GALANIN IN THE MEDIAL SEPTAL AREA IMPAIRS WORKING MEMORY SO BRAIN RESEARCH LA English DT Article DE COEXISTENCE; CHOLINERGIC; GALANIN; HIPPOCAMPUS; MEDIAL SEPTUM; MEMORY; THETA RHYTHM; WORKING MEMORY ID RAT; IMMUNOREACTIVITY; STIMULATION; HIPPOCAMPUS; BEHAVIOR; RECEPTOR; NUCLEUS; LESIONS; CORTEX; SYSTEM AB Galanin, a peptide of 29 amino acids, is co-localized with acetylcholine in a subpopulation of neurons of the medial septal area (MSA) that project to the hippocampus. Galanin reverses the actions of acetylcholine in several biochemical and behavioral procedures, and may be involved in memory processes. To test the possibility that galanin acts on the cell bodies of MSA neurons, two measures of septohippocampal function were assessed following intra-septal microinfusion of galanin or two synthetic fragments of galanin (1-16 and 21-29). The behavioral measure was choice accuracy in a working memory task in a T-maze. The electrophysiological measure was hippocampal theta activity recorded from the dentate hilus. The galanin fragment, 1-16, and the complete peptide, 1-29, decreased choice accuracy and decreased hippocampal theta activity in a dose-dependent fashion. Saline and the 21-29 fragment had no effect on choice accuracy and hippocampal theta. Sensorimotor performance was unaffected. These findings demonstrate that galanin impairs working memory when administered directly into the MSA and suggest that galanin inhibits MSA neural activity. C1 JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218. NIMH,BEHAV NEUROPHARMACOL UNIT,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. FU NINDS NIH HHS [NS-08616] NR 28 TC 75 Z9 75 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 5 PY 1992 VL 582 IS 1 BP 71 EP 77 DI 10.1016/0006-8993(92)90318-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JC223 UT WOS:A1992JC22300009 PM 1379875 ER PT J AU CLARK, M POST, RM WEISS, SRB NAKAJIMA, T AF CLARK, M POST, RM WEISS, SRB NAKAJIMA, T TI EXPRESSION OF C-FOS MESSENGER-RNA IN ACUTE AND KINDLED COCAINE SEIZURES IN RATS SO BRAIN RESEARCH LA English DT Article DE COCAINE; KINDLING, SEIZURE; C-FOS; MESSENGER RNA; HYBRIDIZATION; INSITU; RAT BRAIN ID MOUSE-BRAIN; HIPPOCAMPUS; NEURONS; PROTEIN; STIMULATION; ACTIVATION AB In situ hybridization for c-fos mRNA was performed on brain sections (a) from rats after an acute cocaine-induced seizure or from saline-injected controls and (b) from rats after their first cocaine-kindled seizure, as well as from rats that had not yet developed cocaine-kindled seizures (but were exposed to the same amount of cocaine as those that did exhibit convulsions) and from saline-injected controls. Increased expression of c-fos mRNA was observed in animals demonstrating cocaine-induced seizures acutely or following pharmacological kindling. Rats that experienced acute seizures after cocaine (65 mg/kg) showed pronounced increase in expression of c-fos mRNA in the dentate gyrus of the hippocampus and olfactory bulb. Increases were also observed in several other limbic cortical regions, as well as the striatum and ventromedial hypothalamic nucleus (VMH). In rats that were injected daily with an initially subconvulsive dose of cocaine-HCI (40 mg/kg), the cocaine-kindled seizures induced elevations in c-fos mRNA in the same brain regions as with an acute cocaine-induced seizure with the single exception of the VMH. These findings not only suggest the involvement of limbic, cortical and striatal structures in the cocaine-induced seizure, but also raise the possibility that alterations in the proto-oncogene c-fos and its subsequent impact on gene expression could play a rol in the changes in neural excitability associated with cocaine-induced kindling. RP CLARK, M (reprint author), NIMH,BIOL PSYCHIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 3N212,BETHESDA,MD 20892, USA. NR 32 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 JUN 5 PY 1992 VL 582 IS 1 BP 101 EP 106 DI 10.1016/0006-8993(92)90322-Z PG 6 WC Neurosciences SC Neurosciences & Neurology GA JC223 UT WOS:A1992JC22300013 PM 1498673 ER PT J AU VILLALOBOSMOLINA, R MIYAMOTO, A KOWATCH, MA ROTH, GS AF VILLALOBOSMOLINA, R MIYAMOTO, A KOWATCH, MA ROTH, GS TI ALPHA-1-ADRENOCEPTORS IN PAROTID CELLS - AGE DOES NOT ALTER THE RATIO OF ALPHA-1A AND ALPHA-1B SUBTYPES SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE ALPHA-1-ADRENOCEPTOR SUBTYPES; PAROTID CELLS; AGING ID RECEPTOR SUBTYPES; CHLORETHYLCLONIDINE; RESPONSIVENESS; ACTIVATION AB Epinephrine stimulation of Ca-45(2+) efflux and inositol 1,4,5-trisphosphate ((1,4,5)IP3) production in parotid cell aggregates from mature rats was greatly inhibited (almost-equal-to 70%) by WB 4101 and 5-methylurapidil as compared to a small decrease by chloroethylclonidine (almost-equal-to 30%). The combination of WB 4101 or 5-methylurapidil and chloroethylclonidine completely blocked the action of epinephrine. The same relative inhibition was observed with senescent animals. The results suggest (1) that rat parotids contain both alpha-1-adrenoceptor subtypes, i.e., alpha-1A and alpha-1B, in an approximate functional ratio of 70:30, (2) that this relative ratio is not altered during aging, and (3) that both receptors partially mediate Ca-45(2+) efflux and (1,4,5)IP3 production in this system. C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NR 13 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD JUN 5 PY 1992 VL 226 IS 2 BP 129 EP 131 DI 10.1016/0922-4106(92)90173-S PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HZ784 UT WOS:A1992HZ78400004 PM 1353450 ER PT J AU TSUTSUMI, K ZORAD, S SAAVEDRA, JM AF TSUTSUMI, K ZORAD, S SAAVEDRA, JM TI THE AT2 SUBTYPE OF THE ANGIOTENSIN-II RECEPTORS HAS DIFFERENTIAL SENSITIVITY TO DITHIOTHREITOL IN SPECIFIC BRAIN NUCLEI OF YOUNG-RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Note DE ANGIOTENSIN-II RECEPTOR SUBTYPES; AT2 RECEPTORS; SULFHYDRYL REDUCING AGENTS; DITHIOTHREITOL; LOSARTAN (DUP 753); BRAIN DEVELOPMENT AB We studied the effect of the sulfhydryl reducing agent dithiothreitol on the binding of the angiotensin II agonist [I-125][Sar1]-angiotensin II to AT2 receptors in selected brain areas of young (2-week-old) rats. In the inferior olive and the hypoglossal nucleus, angiotensin II binding to AT2 receptors was insensitive to 5 mM dithiothreitol. Conversely, in the ventral and mediodorsal thalamic, medial geniculate, and oculomotor nuclei, the superior colliculus and the cerebellar cortex, incubation with 5 mM dithiothreitol significantly decreased angiotensin II binding to AT2 receptors to about 40% of control. These data suggest that brain AT2 receptors are heterogeneous with respect to their sensitivity to sulfhydryl reducing agents. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,ROOM 2D-45,BLDG 10,BETHESDA,MD 20892. NR 10 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD JUN 5 PY 1992 VL 226 IS 2 BP 169 EP 173 DI 10.1016/0922-4106(92)90179-Y PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HZ784 UT WOS:A1992HZ78400010 PM 1639112 ER PT J AU LEE, YC OEDA, T DRISCOLL, WJ FALES, HM STROTT, CA AF LEE, YC OEDA, T DRISCOLL, WJ FALES, HM STROTT, CA TI PURIFICATION AND IDENTIFICATION OF THE HEAT-STABLE FACTOR REQUIRED FOR PREGNENOLONE-BINDING PROTEIN-ACTIVITY - EVIDENCE THAT THE FACTOR IS ADENOSINE 3',5'-DIPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PIG ADRENAL-CORTEX; GUINEA-PIG; SOLUBLE FRACTION; PHOSPHORYLATION; ZONES AB This paper presents data identifying adenosine 3',5'-diphosphate (3',5'-ADP) as the small heat-stable factor essential for the active steroid binding complex of the adrenocortical pregnenolone-binding protein (PBP). Factor activity obtained from the boiled supernatant of partially purified PBP was isolated by high performance liquid chromatography using weak anion-exchange and hydrophobic (C18) chromatography sequentially. The purified material retained characteristic factor activity and presented a UV spectrum identical to that for authentic 3',5'-ADP. Mass spectroscopic analysis of the isolated factor revealed an M-H ion of appropriate mass (m/z = 426) and a decomposition pattern for the M-H ion that was consistent with the structure of 3',5'-ADP. The studies presented here demonstrate that authentic 3',5'-ADP can categorically substitute for factor prepared from the soluble fraction of the guinea pig adrenal. Specifically, 3',5'-ADP potentiated ligand binding of partially purified native PBP and restored binding capacity to alkaline phosphatase-inactivated PBP in a dose-dependent manner. As is the case for adrenocortical factor activity, these effects were negated by pretreating the 3',5'-ADP with calf intestinal alkaline phosphatase. Other nucleotides similarly tested, including ADP isomers, were ineffective as factor substitutes. The sulfated form of 3',5'-ADP (i.e. 3'-phosphoadenosine 5-phosphosulfate) demonstrated some potential for restoring binding capacity to phosphatase-inactivated PBP; however, this compound was clearly inhibitory rather than stimulatory for native PBP activity. Taken collectively, the data overwhelmingly demonstrate that 3',5'-ADP is in fact the molecule required by the PBP for high affinity steroid binding complex formation. It is not yet known whether 3',5'-ADP acts allosterically or contributes directly to the structure of the steroid binding site. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,ADRENAL CELL BIOL SECT,BLDG 10,RM B1-L400,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 20 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1992 VL 267 IS 16 BP 10982 EP 10987 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900011 PM 1597440 ER PT J AU YOO, SH LEWIS, MS AF YOO, SH LEWIS, MS TI EFFECTS OF PH AND CA2+ ON MONOMER-DIMER AND MONOMER-TETRAMER EQUILIBRIA OF CHROMOGRANIN-A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-BINDING PROTEIN; RABBIT SKELETAL-MUSCLE; ADRENAL CHROMAFFIN GRANULES; PURIFIED RYANODINE RECEPTOR; AMINO-ACID SEQUENCE; SARCOPLASMIC-RETICULUM; HIGH-AFFINITY; TERMINAL CISTERNAE; MOLECULAR-CLONING; RELEASE CHANNEL AB Chromogranin A is a high capacity, low affinity Ca2+ binding protein which undergoes Ca2+- and pH-dependent conformational changes, and has recently been suggested to play a Ca2+-buffering role in the secretory vesicle of adrenal medullary chromaffin cell, the major inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store of chromaffin cell (Yoo, S. H., and Albanesi, J. P. (1990) J. Biol. Chem. 265, 13446-13448). In the present study, it is shown that chromogranin A exists in a monomer-dimer equilibrium at pH 7.5 and in a monomer-tetramer equilibrium at pH 5.5. The pH appears to be a necessary and sufficient factor determining the types of oligomers formed. Although Ca2+ did not change the type of oligomerization, it had a very significant effect on the values of the thermodynamic parameters characterizing the associations. The DELTA-G0 values for a monomer-dimer equilibrium were -7 to -8 kcal/mol, while those for a monomer-tetramer equilibrium were -20 to -23 kcal/mol. At pH 5.5, the values of DELTA-H0, DELTA-S0, and DELTA-C(p)0 were large and negative in the absence of Ca2+ and large and positive in the presence of 35 mM Ca2+, implying markedly different reaction mechanisms. Extrapolation of the results to 37-degrees-C and 1 mM chromogranin A suggests that chromogranin A is virtually 100% tetramer at pH 5.5 in the presence of 35 mM Ca2+ but is 96% dimer at pH 7.5 in the absence of Ca2+, the two conditions resembling those seen in vivo. These results suggest that chromogranin A is mostly dimer in the endoplasmic reticulum and cis-Golgi area and is essentially all tetramer in the vesicle. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP YOO, SH (reprint author), NIDOCD,CELLULAR BIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 63 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 JUN 5 PY 1992 VL 267 IS 16 BP 11236 EP 11241 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900049 PM 1597459 ER PT J AU CHAKRABORTI, PK GARABEDIAN, MJ YAMAMOTO, KR SIMONS, SS AF CHAKRABORTI, PK GARABEDIAN, MJ YAMAMOTO, KR SIMONS, SS TI ROLE OF CYSTEINE-640, CYSTEINE-656, AND CYSTEINE-661 IN STEROID BINDING TO RAT GLUCOCORTICOID RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TISSUE-CULTURE CELLS; AMINO-ACID-RESIDUES; DNA-BINDING; DEXAMETHASONE 21-MESYLATE; TRANSCRIPTIONAL ENHANCEMENT; MONOCLONAL-ANTIBODY; HORMONE RECEPTORS; SULFHYDRYL-GROUPS; DOMAINS; ACTIVATION AB The involvement of a vicinally spaced dithiol group in steroid binding to the glucocorticoid receptor has been deduced from experiments with the thiol-specific reagent methyl methanethiolsulfonate and the vicinal dithiol-specific reagent sodium arsenite. The vicinally spaced dithiol appears to reside in the 16-kDa trypsin fragment of the receptor, which is thought to contain 3 cysteines (Cys-640, -656, and -661 of the rat receptor) and binds hormone with an approximately 23-fold lower affinity than does the intact 98-kDa receptor. We now report that the steroid binding specificity of preparations of this 16-kDa fragment and the intact receptor are virtually identical. This finding supports our designation of the 16-kDa fragment as a steroid-binding core domain and validates our continued use of this tryptic fragment in studies of steroid binding. To identify the cysteines which comprise the vicinally spaced dithiol group, and to examine further the role of cysteines in steroid binding, a total of five point mutant receptors were prepared: cysteine-to-serine for each suspected cysteine, cysteine-to-glycine for Cys-656, and the C656,661S double mutant. Unexpectedly, each receptor with a single point mutation still bound steroid. Even the double mutant (C656,661S) bound steroid with wild type affinity. These results suggest that none of these cysteines are directly required either for steroid binding to the glucocorticoid receptor or for heat shock protein 90 association with the receptor. However, the presence of Cys-656 was obligatory for covalent labeling of the receptor by [H-3]dexamethasone 21-mesylate. Studies with preparations of the 98 and 16 kDa forms of these mutant receptors revealed both that Cys-656 and -661 comprise the vicinally spaced dithiols reacting with arsenite and that any two of the three thiols could form an intramolecular disulfide after treatment with low concentrations of methyl methanethiolsulfonate. These data, in conjunction with those from experiments on the effects of steric bulk on various receptor functions, support a model for the ligand binding cavity of the receptor that involves all three thiols in a flexible cleft but where thiol-steroid interactions are not essential for binding. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,STEROID HORMONES SECT,BLDG 8,RM B2A-07,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM,SAN FRANCISCO,CA 94143. NR 69 TC 78 Z9 79 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1992 VL 267 IS 16 BP 11366 EP 11373 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900067 PM 1597467 ER PT J AU MENENDEZARIAS, L RISCO, C OROSZLAN, S AF MENENDEZARIAS, L RISCO, C OROSZLAN, S TI ISOLATION AND CHARACTERIZATION OF ALPHA-2-MACROGLOBULIN-PROTEASE COMPLEXES FROM PURIFIED MOUSE MAMMARY-TUMOR VIRUS AND CULTURE SUPERNATANTS FROM VIRUS-INFECTED CELL-LINES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTICATALYTIC PROTEINASE COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; MOLECULAR-WEIGHT PROTEASE; MAMMALIAN-CELLS; TISSUE-CULTURE; RAT-LIVER; GAG; INHIBITORS; RETROVIRUSES; PURIFICATION AB Cleavage of oligopeptide substrates mimicking the maturation sites in the Gag polyproteins of the mouse mammary tumor virus was assayed using lysed virus. Cleavage at the expected P1-P1' positions was detected in four of seven synthetic peptides. However, studies with specific inhibitors of retroviral proteases showed that only two of them could be unequivocally attributed to the viral enzyme. In an attempt to characterize other proteolytic activities that copurify with the virus, we isolated a multicatalytic high molecular mass protease (700 kDa) that copurifies with the virus. This protein has been identified as an alpha-2-macroglobulin-protein complex according to its biochemical properties and ultrastructure. The proteases forming these complexes are mainly serine proteases and can be inhibited by phenylmethylsulfonyl fluoride. However, other compounds such as chymostatin and elastatinal are more effective inhibitors. The relative efficacy of each compound depends on the substrate, since the complexes described herein appear to be multicatalytic. Elastatinal is a very good inhibitor of the cleavages found at Ala-Ala bonds in peptides representing the capsid/nucleocapsid site, while chymostatin inhibits certain cleavages at the carboxyl terminus of bonds involving leucine and valine in three of the substrates used. Therefore, the alpha-2-macroglobulin present in the cell culture medium is able to bind proteases, forming high molecular weight complexes, which are active against peptide substrates, copurify with the virus and are responsible for the nonviral proteolytic activities found in the purified virus. Elastase appears to be the main proteolytic activity which can be detected in the alpha-2-macroglobulin-protease complexes associated with the virus. C1 NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, STRUCT BIOL SECT, FREDERICK, MD 21702 USA. RP MENENDEZARIAS, L (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RI Menendez Arias, Luis /G-2436-2016; OI Menendez Arias, Luis/0000-0002-1251-6640 FU NCI NIH HHS [N01-CO-74101] NR 39 TC 10 Z9 10 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 JUN 5 PY 1992 VL 267 IS 16 BP 11392 EP 11398 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900071 PM 1375941 ER PT J AU SAVARESE, TM WANG, CD FRASER, CM AF SAVARESE, TM WANG, CD FRASER, CM TI SITE-DIRECTED MUTAGENESIS OF THE RAT M(1) MUSCARINIC ACETYLCHOLINE-RECEPTOR - ROLE OF CONSERVED CYSTEINES IN RECEPTOR FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC RECEPTORS; AFFINITY AGONIST BINDING; LIGAND-BINDING; BETA-2-ADRENERGIC RECEPTOR; SULFHYDRYL-REAGENTS; GUANINE-NUCLEOTIDES; SELECTIVELY COUPLE; ANTAGONIST BINDING; DISULFIDE BOND; B82 CELLS AB There are 9 cysteine residues in the rat m1 muscarinic acetylcholine receptor (mAChR) that are conserved among all five mammalian mAChR subtypes sequenced to date. To study the role of these cysteines in rat m1 mAChR function, site-directed mutagenesis was used to convert each Cys residue to Ser, and the mutant receptor genes were transfected into mAChR-deficient Chinese hamster ovary (CHO) cells. Substitution of Cys391 (extracellular loop III) or Cys421 and Cys435 (carboxyl terminus) produces receptors with wild type phenotype. Cells transfected with Ser98 or Ser178 (extracellular loops I and II, respectively) receptor genes display no carbachol-mediated hydrolysis of phosphoinositides (PI), and membranes prepared from these cells do not bind the muscarinic antagonist [H-3] quinuclidinyl benzilate, even though the cells express transcripts of the m1 mAChR as determined by RNA hybridization analysis. Since biochemical evidence suggests that these cysteines form a disulfide bridge (Curtis, C. A. M., Wheatley, M., Bansal, S., Birdsall, N. J. M., Eveleigh, P., Pedder, E. K., Poyner, D., and Hulme, E. C. (1989) 264, 489-495), our findings imply that this disulfide linkage may be critical for formation of the ligand binding domain or for proper protein folding. The Ser394 mAChR (extracellular loop III) exhibits a 44% decrease in efficacy for carbachol-mediated stimulation of PI hydrolysis relative to the wild type receptor, but displays normal ligand binding affinities. The Ser-407 m1 mAChR (transmembrane helix VII) displays a decreased efficacy for eliciting carbachol-mediated PI hydrolysis (39% that of CHO cells transfected with the wild type receptor) and a 4-fold shift to the right in the carbachol dose-response curve, which is consistent with the 4-fold decrease in carbachol affinity at the Ser407 m1 mAChR. In contrast, the Ser417 m1 mAChR (transmembrane helix VII) displays an increase in carbachol affinity and a shift to the left in the carbachol dose-response curve for PI hydrolysis. These findings suggest that cysteine residues in the seventh transmembrane helix of the m1 mAChR may influence agonist binding and the efficiency of receptor activation. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,MOLEC NEUROBIOL SECT,ROCKVILLE,MD 20852. OI Fraser, Claire/0000-0003-1462-2428 FU NCI NIH HHS [CA-01241] NR 45 TC 122 Z9 126 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1992 VL 267 IS 16 BP 11439 EP 11448 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900077 PM 1317867 ER PT J AU MACKAY, K DANIELPOUR, D MILLER, D BORDER, WA ROBBINS, AR AF MACKAY, K DANIELPOUR, D MILLER, D BORDER, WA ROBBINS, AR TI THE 260-KDA TRANSFORMING GROWTH-FACTOR (TGF)-BETA BINDING-PROTEIN IN RAT GLOMERULI IS A COMPLEX COMPRISED OF 170-KDA AND 85-KDA TGF-BETA BINDING-PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR; CELLS AB In a previous study (MacKay, K., Robbins, A. R., Bruce, M. D., and Danielpour, D. (1990) J. Biol. Chem. 265, 9351-9356) we showed that rat glomeruli contain transforming growth factor (TGF)-beta-1 binding proteins with apparent molecular masses of 260, 170, and 85 kDa (Gl-260, Gl-170, Gl-85) as determined by electrophoresis under nonreducing conditions. We demonstrate here that Gl-260 is a complex of 170- and 85-kDa TGF-beta binding proteins. Under denaturing conditions the integrity of Gl-260 is maintained through the cross-linking of one monomer of the disulfide-linked TGF-beta-1 homodimer to Gl-85 and of the other monomer to the 100-kDa subunit of Gl-170. In addition, some Gl-260 complexes are maintained by direct cross-linking of Gl-85 to the 100-kDa subunit of Gl-170. One-dimensional peptide maps of Gl-85 and the 100-kDa subunit of Gl-170 indicate that they have distinctly different ligand binding domains. In contrast, peptide maps of Gl-85 and the type II receptor of normal rat kidney fibroblasts are similar. The biological responses of isolated glomeruli to TGF-beta appear to parallel those of cultured glomerular cells which are without detectable Gl-170 and Gl-260 binding proteins. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV UTAH,SCH MED,DIV NEPHROL,SALT LAKE CITY,UT 84132. RP MACKAY, K (reprint author), NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK43609] NR 20 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 JUN 5 PY 1992 VL 267 IS 16 BP 11449 EP 11454 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900078 PM 1597472 ER PT J AU WADAKIYAMA, Y PETERS, B NOGUCHI, CT AF WADAKIYAMA, Y PETERS, B NOGUCHI, CT TI THE EPSILON-GLOBIN GENE SILENCER - CHARACTERIZATION BY INVITRO TRANSCRIPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FRACTIONATED NUCLEAR EXTRACT; DOMINANT CONTROL REGION; TRANSGENIC MICE; ACCURATE TRANSCRIPTION; NEGATIVE REGULATION; DNA-REPLICATION; GAMMA-GLOBIN; ENHANCER; PROTEIN; EXPRESSION AB K562 human erythroleukemia cells constitutively express epsilon- and gamma- but not beta-globin genes. We have previously shown that the differential expression of globin genes observed in intact K562 cells could be simulated in vitro as K562 nuclear extract (NE) actively transcribes the epsilon-globin (with 2 kilobases of 5'-flanking sequence) and gamma-globin gene DNA templates but not beta-globin gene templates. We have now used the K562 in vitro transcription system to examine a silencer transcriptional control element which has been reported to be localized between -177 and -392 base pairs (bp) 5' of the canonical cap site for the epsilon-globin gene. We find that K562 NE has markedly reduced synthesis of RNA in vitro from epsilon-globin gene DNA deletion templates which contain the silencer sequence, or part thereof, but not the adjacent 5'-positive regulatory region (-453 to -535 bp). Furthermore, those transcripts generated in vitro from DNA templates extending to -453 bp or less of the epsilon-globin gene were not correctly initiated at the canonical cap site. Separating the K562 NE by ion exchange chromatography, we isolated a fraction (F175) transcriptionally active for all tested globin genes including the epsilon-globin gene containing the silencer sequence and a fraction (F50) which contains the trans-acting factors associated with the silencer activity. F50 showed a strong dose-dependent inhibitory effect on correctly initiated epsilon-globin gene transcription directed by either unfractionated K562 NE or F175. This suppression by F50 was not observed on transcriptional activity of the permissive adenovirus 2 major late promoter. In electrophoretic mobility shift assays using the epsilon-globin gene silencer region as probe, F50 and F175 exhibited different DNA binding protein patterns; a specific protein band in F50 appears to be associated with the silencer activity. These studies suggest that this protein may be specifically responsible for the activity of the silencer element of the epsilon-globin gene. The expression and silencing of the epsilon-globin gene during development may be modulated by the interactions of this protein with the cis-acting DNA silencer. C1 NIDDK,CHEM BIOL LAB,BLDG 10,RM 9N307,BETHESDA,MD 20892. NR 45 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1992 VL 267 IS 16 BP 11532 EP 11538 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900091 PM 1597481 ER PT J AU SEGUCHI, T GOTO, Y ONO, M FUJIWARA, T SHIMADA, T KUNG, HF NISHIOKA, M IKEHARA, Y KUWANO, M AF SEGUCHI, T GOTO, Y ONO, M FUJIWARA, T SHIMADA, T KUNG, HF NISHIOKA, M IKEHARA, Y KUWANO, M TI BREFELDIN-A-RESISTANT MUTANTS OF HUMAN EPIDERMOID CARCINOMA CELL-LINE WITH STRUCTURAL-CHANGES OF THE GOLGI-APPARATUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; CULTURED RAT HEPATOCYTES; SECRETORY PROTEINS; INTRACELLULAR-TRANSPORT; VARIANTS RESISTANT; MONENSIN; ACCUMULATION; PATHWAY; ER AB We have isolated brefeldin A (BFA)-resistant cell lines, KB/BF-1 and KB/BF-2, from the human epidermoid carcinoma KB cell line. The BFA-resistant phenotypes have been stably maintained for more than 3 months in the absence of BFA. KB/BF-1 and KB/BF-2 showed 10-30-fold higher resistance to cytotoxicity of BFA but were 2-3-fold more sensitive to monensin and nigericin, than KB cells. KB/BF-1 showed aberrant structures of the Golgi complex with poorly developed cisternae surrounded by many small vesicles. Immunocytochemical studies were done with antibodies against a Golgi-specific antigen (chronic rheumatoid arthritis antigen) and a coatomer subunit (beta-subunit for coat proteins of non-clathrin-coated vesicles). Golgi-specific markers were distributed into the small vesicles which were localized diffusely in cytoplasm of KB/BF-1 cells. Such Golgi markers were observed in a strictly confined perinuclear region of the parental KB cells, whereas in the mutant cells the markers were distributed more diffusely in dot-like structures at perinuclear regions. In addition, when exposed to BFA, the mutant and parental cells showed a different distribution of these markers. Synthesis and maturation of low density lipoprotein receptor showed apparently slower rates in processing of low density lipoprotein receptor in KB/BF-1 and KB/BF-2 cells than those observed in their parental KB cells. Protein secretion in KB/BF-1 and KB/BF-2 cells was about 30% less than that in KB cells. Much less inhibition by BFA on the secretion was observed in KB/BF-1 and KB/BF-2 cells. A BFA-resistant mutation in BFA-resistant KB cell lines appears to affect assembly of the Golgi apparatus as well as some Golgi-specific functions. C1 OITA MED UNIV,DEPT ANAT,OITA 87955,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. FUKUOKA UNIV,SCH MED,DEPT BIOCHEM,FUKUOKA 81401,JAPAN. KAGAWA MED SCH,DEPT INTERNAL MED,KAGAWA 76107,JAPAN. RP SEGUCHI, T (reprint author), OITA MED UNIV,DEPT BIOCHEM,OITA 87955,JAPAN. NR 35 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 5 PY 1992 VL 267 IS 16 BP 11626 EP 11630 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX169 UT WOS:A1992HX16900105 PM 1597488 ER PT J AU LAKSHMAN, MK SAYER, JM JERINA, DM AF LAKSHMAN, MK SAYER, JM JERINA, DM TI SYNTHESIS AND SITE-SPECIFIC INCORPORATION OF A BAY-REGION CIS RING-OPENED TETRAHYDRO EPOXIDE DEOXYADENOSINE ADDUCT INTO A DNA OLIGOMER SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ABSOLUTE STEREOCHEMISTRY; NUCLEOSIDE ADDUCTS; PHENANTHRENE; DIBENZANTHRACENE; 1,2-EPOXIDES AB Chemical synthesis of the 1,2,3,4-tetrahydrophenanthrene 3,4-epoxide adducts resulting from benzylic, cis ring-opening of the epoxide by the exocyclic amino group of 2'-deoxyadenosine (dA) is described. The approach taken consists of coupling (+/-)-cis-3-hydroxy-4-amino-1,2,3,4-tetrahydrophenanthrene with a 6-fluoro analogue of dA in which the furanose hydroxyl groups are protected. The required amino alcohol was obtained by reaction of 1,2-dihydrophenanthrene with osmium tetraoxide to form the cis 3,4-diol, conversion to the trans chlorohydrin benzoate via its orthobenzoate, displacement of the benzylic chloride by azide, hydrolysis to the cis azido alcohol, and reduction to the racemic cis amino alcohol. Coupling of the amino alcohol with the 3',5'-bis-O-(tert-butyldimethylsilyl) derivative of 6-fluoro-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine results in a pair of diastereomers that are readily separated by HPLC on silica gel. Replacement of the previously used pyridine by 2,6-lutidine significantly improved the yield for the coupling step. Both adducts were acetylated on the hydroxyl group of the hydrocarbon and then desilylated on the sugar. Absolute configurations were assigned to the adducts on the basis of the shapes of their CD spectra. The 3S,4R diastereomer (derived from the more polar, late-eluting adduct) was blocked at the 5'-sugar hydroxyl group with the 4,4'-dimethoxytrityl group and allowed to react with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite to produce the desired activated nucleoside. Incorporation into the deoxynucleotide TpGpA*pGpT as the central base proceeded in good yield with minor modifications to the standard DNA synthesizer protocol. C1 NIDDK,BIOORGAN CHEM LAB,OXIDAT MECH SECT,BETHESDA,MD 20892. NR 28 TC 32 Z9 32 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 5 PY 1992 VL 57 IS 12 BP 3438 EP 3443 DI 10.1021/jo00038a037 PG 6 WC Chemistry, Organic SC Chemistry GA HX971 UT WOS:A1992HX97100037 ER PT J AU SCHNEIDER, J AF SCHNEIDER, J TI NIH LEAKS SO SCIENCE LA English DT Letter RP SCHNEIDER, J (reprint author), NIH,OFF DIRECTOR,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 JUN 5 PY 1992 VL 256 IS 5062 BP 1379 EP 1379 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HX337 UT WOS:A1992HX33700008 PM 1604308 ER PT J AU KANG, SM TRAN, AC GRILLI, M LENARDO, MJ AF KANG, SM TRAN, AC GRILLI, M LENARDO, MJ TI NF-KAPPA-B SUBUNIT REGULATION IN NONTRANSFORMED CD4+ LYMPHOCYTES-T SO SCIENCE LA English DT Article ID ANTIGEN-PRESENTING CELLS; HUMAN INTERLEUKIN-2 GENE; DNA-BINDING SUBUNIT; PROTEIN-BINDING; REL ONCOGENE; EXPRESSION; ENHANCER; ACTIVATION; IDENTIFICATION; TRANSCRIPTION AB Regulation of interleukin-2 (IL-2) gene expression by the p50 and p65 subunits of the DNA binding protein NF-kappa-B was studied in nontransformed CD4+ T lymphocyte clones. A homodimeric complex of the NF-kappa-B p50 subunit was found in resting T cells. The amount of p50-p50 complex decreased after full antigenic stimulation, whereas the amount of the NF-kappa-B p50-p65 heterodimer was increased. Increased expression of the IL-2 gene and activity of the IL-2 kappa-B DNA binding site correlated with a decrease in the p50-p50 complex. Overexpression of p50 repressed IL-2 promoter expression. The switch from p50-p50 to p50-p65 complexes depended on a protein that caused sequestration of the p50-p50 complex in the nucleus. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 66 TC 302 Z9 313 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 5 PY 1992 VL 256 IS 5062 BP 1452 EP 1456 DI 10.1126/science.1604322 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HX337 UT WOS:A1992HX33700038 PM 1604322 ER PT J AU LI, BQ KAPLAN, D KUNG, HF KAMATA, T AF LI, BQ KAPLAN, D KUNG, HF KAMATA, T TI NERVE GROWTH-FACTOR STIMULATION OF THE RAS-GUANINE NUCLEOTIDE EXCHANGE FACTOR AND GAP ACTIVITIES SO SCIENCE LA English DT Article ID GTPASE ACTIVATING PROTEIN; PC12 CELLS; TYROSINE PHOSPHORYLATION; BOVINE BRAIN; DIFFERENTIATION; MICROINJECTION; PURIFICATION; P21RAS; ONCOGENES; INDUCTION AB The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LAB,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101] NR 37 TC 121 Z9 122 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 5 PY 1992 VL 256 IS 5062 BP 1456 EP 1459 DI 10.1126/science.1604323 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HX337 UT WOS:A1992HX33700039 PM 1604323 ER PT J AU ROTROSEN, D YEUNG, CL LETO, TL MALECH, HL KWONG, CH AF ROTROSEN, D YEUNG, CL LETO, TL MALECH, HL KWONG, CH TI CYTOCHROME-B558 - THE FLAVIN-BINDING COMPONENT OF THE PHAGOCYTE NADPH OXIDASE SO SCIENCE LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; RESPIRATORY BURST OXIDASE; AMINO-ACID-SEQUENCE; HUMAN-NEUTROPHILS; NADPH-CYTOCHROME-P-450 REDUCTASE; FLAVOPROTEIN COMPONENT; GLUTATHIONE-REDUCTASE; DIPHENYLENE IODONIUM; GENERATING OXIDASE; PLASMA-MEMBRANE AB The phagocyte respiratory burst oxidase is a flavin-adenine dinucleotide (FAD)-dependent dehydrogenase and an electron transferase that reduces molecular oxygen to superoxide anion, a precursor of microbicidal oxidants. Several proteins required for assembly of the oxidase have been characterized, but the identity of its flavin-binding component has been unclear. Oxidase activity was reconstituted in vitro with only the purified oxidase proteins p47phox, p67phox, Rac-related guanine nucleotide (GTP)-binding proteins, and membrane-bound cytochrome b558. The reconstituted oxidase required added FAD, and FAD binding was localized to cytochrome b558. Alignment of the amino acid sequence of the beta-subunit of cytochrome b558 (gp91phox) with other flavoproteins revealed similarities to the nicotinamide adenine dinucleotide phosphate (reduced) (NADPH)-binding domains. Thus flavocytochrome b558 is the only obligate electron transporting component of the NADPH oxidase. RP ROTROSEN, D (reprint author), NIAID,HOST DEF LAB,BETHESDA,MD 20892, USA. NR 48 TC 352 Z9 355 U1 2 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 5 PY 1992 VL 256 IS 5062 BP 1459 EP 1462 DI 10.1126/science.1318579 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HX337 UT WOS:A1992HX33700040 PM 1318579 ER PT J AU YUSUF, S GARG, R HELD, P GORLIN, R AF YUSUF, S GARG, R HELD, P GORLIN, R TI NEED FOR A LARGE RANDOMIZED TRIAL TO EVALUATE THE EFFECTS OF DIGITALIS ON MORBIDITY AND MORTALITY IN CONGESTIVE-HEART-FAILURE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT SYMP ON MANAGEMENT OF HEART FAILURE IN THE 1990S : A REASSESSMENT OF THE ROLE OF DIGOXIN THERAPY CY JUL 27-28, 1991 CL NEW YORK, NY SP BURROUGHS WELLCOME ID ACUTE MYOCARDIAL-INFARCTION; SINUS RHYTHM; DIGOXIN; SURVIVAL; THERAPY; PLACEBO; OUTPATIENTS; WITHDRAWAL; DRUG AB Despite major advances in the prevention and treatment of cardiovascular diseases, the incidence and prevalence af congestive heart failure (CHF) have been increasing in recent years. As the average age of the population increases, the prevalence of CHF is expected to continue to increase. The number deaths in which CHF was considered the underlying or contributing increased from 51,000 in 1955 to 274,000 by 1988 in the United States. Even accounting for population growth and an increase in the number of elderly, this represents a 2-fold increase. Additionally, CHF was responsible for about 643,000 hospitalizations in 1988. Digitalis is one of the drugs most commonly prescribed for CHF and has been used for >200 years. In 1990, digoxin was one of the most commonly prescribed drugs in the United States, accounting for > 21 million prescriptions. There has been little decline in the drug's use over the last 5 years, indicating that newer treatments for CHF have not replaced the widespread use of digitalis. Despite these findings, considerable controversy surrounds the appropriateness of its role and value in treating CHF patients who are in sinus rhythm. A number af recent, uncontrolled studies have arrived at apparently contradictory conclusions concerning the effects of digitalis on mortality in postmyocardial infarction and heart failure patients. A large, double-blind, randomized, controlled clinical trial to evaluate the effects of digitalis on mortality, morbidity and quality of life is being sponsored by the National Heart, Lung, and Institute in conjunction with the Department of Veterans Affairs Cooperative Studies Program. Patients with CHF and an ejection fraction less-than-or-equal-to 0.45 will be randomized to receive digoxin or placebo along with other standard therapy. Patients with an ejection fraction >0.45 also will be enrolled in a parallel but separate ancillary study. Patient recruitment started in early March 1991, and about 7,500 to 8,000 patients are expected to be enrolled over 3 years and followed for a minimum of 2 further years or until the end of the study. Results are expected to become available in 1995 or 1996. C1 MT SINAI HOSP,NEW YORK,NY. GOTHENBURG UNIV,S-41124 GOTHENBURG,SWEDEN. RP YUSUF, S (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,FED BLDG,BETHESDA,MD 20892, USA. NR 41 TC 55 Z9 55 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 JUN 4 PY 1992 VL 69 IS 18 BP G64 EP G70 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HX955 UT WOS:A1992HX95500008 PM 1626493 ER PT J AU TYBULEWICZ, VLJ TREMBLAY, ML LAMARCA, ME WILLEMSEN, R STUBBLEFIELD, BK WINFIELD, S ZABLOCKA, B SIDRANSKY, E MARTIN, BM HUANG, SP MINTZER, KA WESTPHAL, H MULLIGAN, RC GINNS, EI AF TYBULEWICZ, VLJ TREMBLAY, ML LAMARCA, ME WILLEMSEN, R STUBBLEFIELD, BK WINFIELD, S ZABLOCKA, B SIDRANSKY, E MARTIN, BM HUANG, SP MINTZER, KA WESTPHAL, H MULLIGAN, RC GINNS, EI TI ANIMAL-MODEL OF GAUCHERS-DISEASE FROM TARGETED DISRUPTION OF THE MOUSE GLUCOCEREBROSIDASE GENE SO NATURE LA English DT Article ID CELLS; MUTATIONS AB GAUCHER's disease is the most prevalent lysosomal storage disorder in humans and results from an autosomally inherited deficiency of the enzyme glucocerebrosidase (beta-D-glucosyl-N-acylsphingosine glucohydrolase) 1-6, which is responsible for degrading the sphingolipid glucocerebroside. An animal model for Gaucher's disease would be important for investigating its phenotypic diversity and pathogenesis and for evaluating therapeutic approaches. A naturally occurring canine model has been reported but not propagated 7. Attempts to mimic the disease in animals by inhibiting glucocerebrosidase have been inadequate 8. Here we generate an animal model for Gaucher's disease by creating a null allele in embryonic stem cells through gene targeting and using these genetically modified cells to establish a mouse strain carrying the mutation 9,10. Mice homozygous for this mutation have < 4% Of normal glucocerebrosidase activity, die within twenty-four hours of birth and store glucocerebroside in lysosomes of cells of the reticuloendothelial system. C1 NIMH,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. ERASMUS UNIV,DEPT CELL BIOL & GENET,3000 DR ROTTERDAM,NETHERLANDS. NR 25 TC 217 Z9 219 U1 2 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 4 PY 1992 VL 357 IS 6377 BP 407 EP 410 DI 10.1038/357407a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HX172 UT WOS:A1992HX17200064 PM 1594045 ER PT J AU PRAS, E AKSENTIJEVICH, I GRUBERG, L BALOW, JE PROSEN, L DEAN, M STEINBERG, AD PRAS, M KASTNER, DL AF PRAS, E AKSENTIJEVICH, I GRUBERG, L BALOW, JE PROSEN, L DEAN, M STEINBERG, AD PRAS, M KASTNER, DL TI MAPPING OF A GENE CAUSING FAMILIAL MEDITERRANEAN FEVER TO THE SHORT ARM OF CHROMOSOME-16 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LINKAGE ANALYSIS; DNA; AMYLOIDOSIS; IDENTIFICATION; POLYSEROSITIS; C5A-INHIBITOR; LOCALIZATION; ARMENIANS; FREQUENCY; COMMITTEE AB Background. Familial Mediterranean fever is an autosomal-recessive disease characterized by acute attacks of fever with sterile peritonitis, pleurisy, or synovitis. The biochemical basis of the disease is unknown, but determining the chromosomal location of the gene for the disorder should be a first step toward defining the biochemical events. Methods and Results. As part of a systematic genome-wide search, we sought evidence of linkage between familial Mediterranean fever and chromosome 16 DNA markers in 27 affected non-Ashkenazi Jewish families from Israel. Two loci from the subtelomeric region of the short arm of chromosome 16 (16p) had lod scores sufficient to establish linkage (a score greater-than-or-equal-to 3). One DNA marker (D16S84) gave a maximal lod score of 9.17 (odds of 10(9.17) to 1 in favor of linkage) at a recombination frequency (theta) of 0.04. A probe associated with the hemoglobin-alpha complex (5'HVR) gave a maximal lod score of 14.47 at a theta of 0.06. Multipoint linkage analysis indicated that the following was the most likely gene order: the centromere, the gene for familial Mediterranean fever, D16S84, hemoglobin-alpha, and the telomere. The maximal multipoint lod score was 19.86. There was a striking degree of homozygosity at chromosome 16p loci in the affected offspring of eight consanguineous couples. Conclusions. The gene that causes familial Mediterranean fever in non-Ashkenazi Jews maps to the short arm of chromosome 16. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BLDG 6,RM 112,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT MED,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 41 TC 202 Z9 204 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 4 PY 1992 VL 326 IS 23 BP 1509 EP 1513 DI 10.1056/NEJM199206043262301 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA HW972 UT WOS:A1992HW97200001 PM 1579134 ER PT J AU HEALY, B AF HEALY, B TI FROM FORM TO FUNCTION - BETTER IMAGING TECHNIQUES EXTEND STUDY OF LIVING SYSTEMS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 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 JUN 3 PY 1992 VL 267 IS 21 BP 2863 EP 2863 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HW133 UT WOS:A1992HW13300005 PM 1583743 ER PT J AU CALLAHAN, R AF CALLAHAN, R TI P53 MUTATIONS, ANOTHER BREAST-CANCER PROGNOSTIC FACTOR SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP CALLAHAN, R (reprint author), NCI,DIV CANC BIOL DIAGNOSIS & CTR,TUMOR IMMUNOL & BIOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 15 TC 75 Z9 75 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 3 PY 1992 VL 84 IS 11 BP 826 EP 827 DI 10.1093/jnci/84.11.826 PG 2 WC Oncology SC Oncology GA HW636 UT WOS:A1992HW63600001 PM 1593647 ER PT J AU OCHOA, JB CURTI, B PEITZMAN, AB SIMMONS, RL BILLIAR, TR HOFFMAN, R RAULT, R LONGO, DL URBA, WJ OCHOA, AC AF OCHOA, JB CURTI, B PEITZMAN, AB SIMMONS, RL BILLIAR, TR HOFFMAN, R RAULT, R LONGO, DL URBA, WJ OCHOA, AC TI INCREASED CIRCULATING NITROGEN-OXIDES AFTER HUMAN TUMOR-IMMUNOTHERAPY - CORRELATION WITH TOXIC HEMODYNAMIC-CHANGES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; NITRIC-OXIDE; L-ARGININE; NITRATE BIOSYNTHESIS; INTERFERON-GAMMA; NECROSIS-FACTOR; BLOOD-PRESSURE; ENDOTOXIN; CANCER; INVIVO AB Background: Toxicity to interleukin-2 (IL-2) tumor immunotherapy is manifested principally by the vascular leak syndrome, hypotension, and a hyperdynamic response with low systemic vascular resistance. Nitric oxide (.N = O), a recently discovered biological mediator of vascular smooth muscle relaxation, is produced in increased amounts by numerous cell types exposed to a number of inflammatory cytokines. Purpose: Our purpose was to determine if there is an increased production of .N = O in patients receiving IL-2 tumor immunotherapy, and, if so, whether increases in .N = O production correlate with hemodynamic instability. Methods: Twelve patients undergoing immunotherapy trials with IL-2 and anti-CD3 monoclonal antibody-activated lymphocytes (T-AK cells) were studied. Plasma levels of nitrate (NO3-), the stable end metabolic product of .N = O synthesis, were measured before and at the end of IL-2 treatment cycles. Results: We observed a ninefold increase in plasma levels of NO3 in patients after 7 days of treatment (P < .0001). A significant decrease in both systolic and diastolic blood pressures was observed in all patients (P < .001). Conclusions: We propose that mediated induction of .N = O synthase enzyme leads to progressive increases in .N = O production which, in turn, produces clinically significant hypotension. Implications: Since .N = O synthesis can be competitively inhibited by L-arginine analogues, a possible pharmacologic modulation of .N = O production could potentially contribute to better management of toxic side effects seen in IL-2 cancer therapies. C1 UNIV PITTSBURGH,DEPT MED,PITTSBURGH,PA 15261. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21701. RP OCHOA, JB (reprint author), UNIV PITTSBURGH,DEPT SURG,497 SCAIFE HALL,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [N01-CO-74102]; NIGMS NIH HHS [GM-44100, GM-37753] NR 30 TC 135 Z9 136 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 3 PY 1992 VL 84 IS 11 BP 864 EP 867 DI 10.1093/jnci/84.11.864 PG 4 WC Oncology SC Oncology GA HW636 UT WOS:A1992HW63600011 PM 1375656 ER PT J AU FREY, CM MCMILLEN, MM COWAN, CD HORM, JW KESSLER, LG AF FREY, CM MCMILLEN, MM COWAN, CD HORM, JW KESSLER, LG TI REPRESENTATIVENESS OF THE SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS PROGRAM DATA - RECENT TRENDS IN CANCER MORTALITY-RATES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article AB Background: Mortality, incidence, and survival rates are the primary measures used by the National Cancer Institute (NCI) to monitor cancer in the United States. The Surveillance, Epidemiology, and End Results (SEER) data system collects data on all cancers diagnosed among residents in geographically defined populations, which comprise about 10% of the U.S. population. This data system is the major component of the NCI system for tracking these rates. Thus, it is important to assess the degree to which SEER data are representative of the entire U.S. population. Purpose: National data on mortality, but not on incidence or survival, are available from the National Center for Health Statistics. These data provide a census against which mortality data from the subset of the SEER regions may be compared. Methods: Multivariate regression analyses of age-adjusted mortality rates from 1975 to 1988, computed for the SEER areas and for the entire United States, were performed for race- and sex-specific data from 15 cancer sites. Representativeness was evaluated by testing for differences in trends and levels between the data from the U.S. population and those from the SEER Program. Results: Data from the SEER regions reflected the correct direction of trend for all sites, although some race-, sex-, and site-specific differences existed for the magnitude of the trends and levels of mortality when compared with data from the U.S. population. Conclusions: The demonstration that data from the SEER population do occasionally yield mortality rates that differ from those for the entire U.S. population suggests that data from the SEER coverage population are, in some cases, not representative of the greater U.S. population. Implications: This issue is of particular relevance to the interpretation of incidence measures, computed from the SEER data, for which there is no national data-base. Future efforts should be directed at a better understanding of how the SEER population differs from the U.S. population so that SEER rates can be adjusted to be more nationally representative. C1 OPIN RES CORP,WASHINGTON,DC. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP FREY, CM (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 12 TC 78 Z9 79 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 3 PY 1992 VL 84 IS 11 BP 872 EP 877 DI 10.1093/jnci/84.11.872 PG 6 WC Oncology SC Oncology GA HW636 UT WOS:A1992HW63600013 PM 1593655 ER PT J AU TORRI, V SIMON, R RUSSEKCOHEN, E MIDTHUNE, D FRIEDMAN, M AF TORRI, V SIMON, R RUSSEKCOHEN, E MIDTHUNE, D FRIEDMAN, M TI RELATIONSHIP BETWEEN RESPONSE AND SURVIVAL IN PATIENTS WITH ADVANCED OVARIAN-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID RANDOMIZED TRIAL; COMPARING CISPLATIN; CYCLOPHOSPHAMIDE; DOXORUBICIN C1 NCI,DIV CANC TREATMENT,EXECUT PLAZA N,RM 739,BETHESDA,MD 20892. NR 7 TC 5 Z9 5 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 3 PY 1992 VL 84 IS 11 BP 899 EP 899 DI 10.1093/jnci/84.11.899 PG 1 WC Oncology SC Oncology GA HW636 UT WOS:A1992HW63600018 PM 1593657 ER PT J AU FOLEY, CK PEDERSEN, LG CHARIFSON, PS DARDEN, TA WITTINGHOFER, A PAI, EF ANDERSON, MW AF FOLEY, CK PEDERSEN, LG CHARIFSON, PS DARDEN, TA WITTINGHOFER, A PAI, EF ANDERSON, MW TI SIMULATION OF THE SOLUTION STRUCTURE OF THE H-RAS P21-GTP COMPLEX SO BIOCHEMISTRY LA English DT Article ID TWO-DIMENSIONAL NMR; RELATE 2 SETS; TRIPHOSPHATE CONFORMATION; ACTIVATING PROTEIN; MOLECULAR-DYNAMICS; BINDING DOMAIN; GTP HYDROLYSIS; NUCLEIC-ACIDS; FORCE-FIELD; P21 AB An unconstrained simulation of the GTP-bound form of the H-ras protein p21 is performed in an aqueous environment with charge-neutralizing counterions. The simulation is compared to the 1.35-angstrom structure of Pai et al. [(1990) EMBO J. 9, 2351] and a proposed alternate structure, in which the loop at residues 60-65 is modeled into a form which may activate a water molecule for the GTP hydrolysis. The simulation suggests that some protein intermolecular H-bond contacts which are present in the crystal structure are lost in the solvation process and this loss may lead to localized refolding of the molecule. For instance, we find that the gamma-phosphate of the GTP has somewhat weaker contact with the protein in the simulation structure. The antiparallel beta-sheet (residues 38-57) partially melts. The 60-65 loop, which is hypervariable in the X-ray study, is initially relatively distant from the gamma-phosphate region. However, this loop moves so as to sample the space around the gamma-phosphate. For a significant fraction of the simulation time, forms similar to the alternate structure are observed, and a water molecule is localized near the hydrolytic site. The molecular dynamics simulations of p21-GTP in solution support a postulated hydrolysis mechanism for the biological inactivation of the nucleotide complex based on crystallographic data. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. CRAY RES INC,RES TRIANGLE PK,NC 27709. MAX PLANCK INST MED RES,BIOPHYS ABT,W-6900 HEIDELBERG 1,GERMANY. RP DARDEN, TA (reprint author), NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. RI Pai, Emil/D-2526-2013; Pedersen, Lee/E-3405-2013; OI Pedersen, Lee/0000-0003-1262-9861; Foley, Charles/0000-0001-6578-9629 FU NHLBI NIH HHS [HL27995] NR 36 TC 44 Z9 44 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 2 PY 1992 VL 31 IS 21 BP 4951 EP 4959 DI 10.1021/bi00136a005 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HX170 UT WOS:A1992HX17000005 PM 1599919 ER PT J AU VAKKUR, M BROADHEAD, WE ANDOLSEK, KM MAGRUDER, K AF VAKKUR, M BROADHEAD, WE ANDOLSEK, KM MAGRUDER, K TI IMPACT OF A SUBSTANCE-ABUSE CURRICULUM ON PRIMARY CARE PHYSICIANS ATTITUDES SO ACADEMIC MEDICINE LA English DT Note C1 DUKE UNIV,SCH MED,DURHAM,NC 27706. DUKE UNIV,MED CTR,DEPT COMMUNITY & FAMILY MED,DURHAM,NC 27710. NIMH,BETHESDA,MD 20892. FU NIAAA NIH HHS [R01 AA 07138] NR 1 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1992 VL 67 IS 6 BP 414 EP 414 DI 10.1097/00001888-199206000-00019 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA HZ569 UT WOS:A1992HZ56900020 PM 1596346 ER PT J AU ELTOUM, IA SULAIMAN, S ISMAIL, BM ALI, MMM ELFATIH, M HOMEIDA, MMA AF ELTOUM, IA SULAIMAN, S ISMAIL, BM ALI, MMM ELFATIH, M HOMEIDA, MMA TI EVALUATION OF HEMATURIA AS AN INDIRECT SCREENING-TEST FOR SCHISTOSOMIASIS-HAEMATOBIUM - A POPULATION-BASED STUDY IN THE WHITE-NILE PROVINCE, SUDAN SO ACTA TROPICA LA English DT Article DE SCHISTOSOMA-HAEMATOBIUM; HEMATURIA; REAGENT STRIPS; SUDAN ID URINARY SCHISTOSOMIASIS; INFECTION; HEMATURIA; SCHOOLCHILDREN AB Haematuria elicited in the history, seen macroscopically or detected by reagent strips, was used as an indirect screening test for Schistosoma haematobium infection in Um-Hani Irrigation Scheme in the White Nile province, Sudan. These approaches were used separately or combined in different sequences. Reagent strips alone detected 81% of cases and 88% of those who excreted 50 egg/10 ml of urine or more. The sequence of observation of gross haematuria followed by screening with reagent strips and then taking history of haematuria had the highest sensitivity of all the orders, 0.87, and it saved 18% of reagent strips. If history and inspection were done first, followed by reagent strips, the sensitivity would be 0.86 and 47% of strips would be saved. The specificity of haematuria as a diagnostic index for schistosomiasis, however, was low. C1 MINIST HLTH SUDAN,DEPT PATHOL,KHARTOUM,SUDAN. MINIST HLTH SUDAN,FAC MED,DEPT MED,KHARTOUM,SUDAN. MINIST HLTH SUDAN,BILHARZIA RES UNIT,KHARTOUM,SUDAN. RP ELTOUM, IA (reprint author), NIAID,SUDAN MRC NIH USA MED PARASITOL PROJECT,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-706X J9 ACTA TROP JI Acta Trop. PD JUN PY 1992 VL 51 IS 2 BP 151 EP 157 DI 10.1016/0001-706X(92)90057-5 PG 7 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA JC125 UT WOS:A1992JC12500006 PM 1354933 ER PT J AU COOPER, JK MUNGAS, D AF COOPER, JK MUNGAS, D TI SEROTONIN RESPONSE IN SWEET-FOOD CRAVING ALZHEIMERS-DISEASE SUBJECTS SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; DIETARY BEHAVIOR; FENFLURAMINE; PROLACTIN; SEROTONIN AB Abnormal sweet-food craving may occur in subjects with Alzheimer's disease. This behavior may be due to abnormalities in the brain serotonin system. Fenfluramine stimulates the brain serotonin neurosystem, producing an increase in systemic prolactin. Using the fenfluramine stimulation test, brain serotonin system response was evaluated in 12 subjects with probable Alzheimer's disease. The subjects' caregivers completed questionnaires concerning subject food preferences and behaviors. Alzheimer's disease subjects with sweet-food craving were found to. have a significantly higher response to fenfluramine than non sweet-food craving subjects. This preliminary study is limited by small sample size. Allowing for assumptions concerning central nervous system regulatory processes, the data suggest a possible role for the serotonin system in sweet-food craving in Alzheimer's disease. RP COOPER, JK (reprint author), NIA,BLDG 31,ROOM 5C27,BETHESDA,MD 20892, USA. RI Mungas, Dan/E-6810-2011 NR 0 TC 5 Z9 6 U1 1 U2 3 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD JUN PY 1992 VL 4 IS 2 BP 165 EP 169 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JF968 UT WOS:A1992JF96800009 PM 1504133 ER PT J AU YARCHOAN, R MITSUYA, H BRODER, S AF YARCHOAN, R MITSUYA, H BRODER, S TI THE IMMUNOLOGY OF HIV-INFECTION - IMPLICATIONS FOR THERAPY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; AIDS-RELATED COMPLEX; TUMOR-NECROSIS-FACTOR; IMMUNE-DEFICIENCY SYNDROME; T-CELL CLONES; ZIDOVUDINE AZT; PHASE-I; ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE AB It is known that antiretroviral drugs can induce immunologic improvement in patients with acquired immunodeficiency syndrome (AIDS) and other manifestations of HIV infection. However, the improvements so attained are often partial and transient. This may result from a number of factors, including incomplete inhibition of human immunodeficiency virus (HIV) replication by available agents, the development of viral drug resistance, the effect of cytokines, or thymic damage. An understanding of this problem may be important in further development of AIDS therapies. It will also be important to learn how to best assess the response to various therapies. In this regard, the CD4 count is evolving as a mortality risk indicator in AIDS and as such may find utility in assessing new therapeutic approaches. We have observed that in a cohort of py men receiving antiretroviral therapy in a research environment, nearly all deaths occurred in individuals with fewer than 50 CD4 cells/mm3. However, the relationship between the CD4 count and the hazard of dying may be influenced by a number of factors (e.g., active intravenous drug use, extreme poverty, etc.), and further studies are needed to define the relationship between CD4 and clinical endpoints under a variety of conditions. RP YARCHOAN, R (reprint author), NCI,MED BRANCH,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 104 TC 7 Z9 7 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1992 VL 8 IS 6 BP 1023 EP 1031 DI 10.1089/aid.1992.8.1023 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JG873 UT WOS:A1992JG87300005 PM 1503817 ER PT J AU HUSSON, RN PIZZO, PA AF HUSSON, RN PIZZO, PA TI THE USE OF NUCLEOSIDE ANALOGS IN THE TREATMENT OF HIV-INFECTED CHILDREN SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; TERM ZIDOVUDINE THERAPY; PEDIATRIC-PATIENTS; CUBIC MILLIMETER; ORAL ZIDOVUDINE; DOUBLE-BLIND; INFANTS; TYPE-1 C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N240,BETHESDA,MD 20892. NR 45 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1992 VL 8 IS 6 BP 1059 EP 1064 DI 10.1089/aid.1992.8.1059 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JG873 UT WOS:A1992JG87300009 PM 1323984 ER PT J AU VERONESE, FD RAHMAN, R PAL, R BOYER, C ROMANO, J KALYANARAMAN, VS NAIR, BC GALLO, RC SARNGADHARAN, MG AF VERONESE, FD RAHMAN, R PAL, R BOYER, C ROMANO, J KALYANARAMAN, VS NAIR, BC GALLO, RC SARNGADHARAN, MG TI DELINEATION OF IMMUNOREACTIVE, CONSERVED REGIONS IN THE EXTERNAL GLYCOPROTEIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HTLV-III LAV; MONOCLONAL-ANTIBODIES; ENVELOPE PROTEIN; MONONUCLEAR PHAGOCYTES; TRANSMEMBRANE PROTEIN; NUCLEOTIDE-SEQUENCE; CD4-BINDING DOMAIN; HIV INFECTION; GP120; CD4 AB Immunization of mice and rats with purified external glycoprotein gp120 from two divergent human immunodeficiency virus type 1 (HIV-1) isolates resulted in the development of seven hybridomas secreting monoclonal antibodies able to recognize regions of gp120 which are common among divergent strains of HIV-1. These monoclonal antibodies cross-reacted with env glycoproteins from one African (Rutz), one Haitian (RF), and three North American viral isolates, namely IIIB, MN, and 451 by either immunoblot or radioimmunoprecipitation assays. All recognized denatured gp120 in immunoblots with the exception of one which required a conformationally intact glycoprotein for reactivity. The gp120 epitopes identified by these antibodies were mapped by screening of an env gene library in the lambda gt11 expression system. Three out of four epitopes were found to reside in the amino-terminal half of gp120 (Cys9 to Cys35, Thr44 to Glu72 and Val108 to Met130 ), the other was located in the middle region (Thr221 to Ser255). By virtue of their extent of cross-reactivity these reagents might provide a unique resource for the detection of new viral isolates related to HIV-1. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP VERONESE, FD (reprint author), ADV BIOSCI LABS INC,DEPT CELL BIOL,5510 NICHOLSON LANE,KENSINGTON,MD 20895, USA. NR 31 TC 20 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 1992 VL 8 IS 6 BP 1125 EP 1132 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JG873 UT WOS:A1992JG87300018 ER PT J AU MEADOWS, GG WALLENDAL, M KOSUGI, A WUNDERLICH, J SINGER, DS AF MEADOWS, GG WALLENDAL, M KOSUGI, A WUNDERLICH, J SINGER, DS TI ETHANOL INDUCES MARKED CHANGES IN LYMPHOCYTE POPULATIONS AND NATURAL-KILLER-CELL ACTIVITY IN MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CELLULAR DEPLETION; LYMPHOCYTE SUBPOPULATIONS; NK ACTIVITY ID EXPRESSION; TOXICITY AB Treatment of mice in vivo with 5% w/v ethanol given in a liquid diet causes marked changes in spleen, peripheral blood, and thymus lymphocytes. In both the thymus and spleen, there is an acute cellular depletion resulting in a significant decrease in gross tissue size and cell number. In spleen and peripheral blood, the percentage of T lymphocytes is increased relative to B lymphocytes, but the ratio of CD4+/CD8+ T cell sub-populations remains unchanged. Splenic natural killer (NK) cell activity is increased in ethanol-consuming mice, although the percentage of NK1.1+ cells is relatively unchanged. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. WASHINGTON STATE UNIV,COLL PHARM,PULLMAN,WA 99164. FU NIAAA NIH HHS [AA08386] NR 17 TC 48 Z9 48 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1992 VL 16 IS 3 BP 474 EP 479 DI 10.1111/j.1530-0277.1992.tb01403.x PG 6 WC Substance Abuse SC Substance Abuse GA HZ911 UT WOS:A1992HZ91100010 PM 1626648 ER PT J AU LANCASTER, FE AF LANCASTER, FE TI ALCOHOL, NITRIC-OXIDE, AND NEUROTOXICITY - IS THERE A CONNECTION - A REVIEW SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE NEUROTOXICITY; NITRIC OXIDE; ALCOHOL; EXCITOTOXICITY; GLUTAMATE ID SENSITIVE CALCIUM CHANNELS; NADPH-DIAPHORASE; NMDA RECEPTOR; NEUROPEPTIDE-Y; NERVOUS-SYSTEM; ETHANOL; ARGININE; NEURONS; BRAIN; SOMATOSTATIN AB A hypothesis is presented to explain the influence of alcohol on glutamate generated excitotoxicity. Chronic alcohol exposure is reported to increase glutamate-N-methyl-D-aspartate (NMDA) receptors and calcium ion channel activity, resulting in the neurotoxicity and seizure activity associated with alcohol withdrawal in certain persons. Recent information indicates that nitric oxide is responsible for the neurotoxicity associated with excessive glutamate stimulation of NMDA receptors. Thus, it is hypothesized that nitric oxide is involved in producing the neurotoxicity and cell disturbances associated with chronic alcohol exposure. RP LANCASTER, FE (reprint author), NIAAA,DIV BASIC RES,NEUROSCI & BEHAV RES BRANCH,5600 FISHERS LANE,ROOM 16C-05,ROCKVILLE,MD 20857, USA. NR 53 TC 62 Z9 62 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1992 VL 16 IS 3 BP 539 EP 541 DI 10.1111/j.1530-0277.1992.tb01413.x PG 3 WC Substance Abuse SC Substance Abuse GA HZ911 UT WOS:A1992HZ91100020 PM 1320808 ER PT J AU DAWSON, DA HARFORD, TC GRANT, BF AF DAWSON, DA HARFORD, TC GRANT, BF TI FAMILY HISTORY AS A PREDICTOR OF ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE FAMILY HISTORY; ALCOHOL DEPENDENCE; ALCOHOLISM ID ADOPTEES RAISED APART; RELATIVES; MEN AB The effects of various levels of positive family history of alcoholism on the probability of past year alcohol dependence were investigated using a general population sample of 23,152 drinkers 18 years of age and older. Forty percent reported a positive family history. After adjustment for age, race, gender, and poverty and compared with persons with a negative family history, the odds of alcohol dependence were increased by 45% among persons with alcoholism in second or third degree relatives only, by 86% among those with alcoholism in first degree relatives only, and by 167% among those with alcoholism in first and second or third degree relatives. The effects of family history did not vary among population subgroups as defined by age, race, gender, and poverty. RP DAWSON, DA (reprint author), NIAAA,DBE,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20852, USA. NR 17 TC 86 Z9 90 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1992 VL 16 IS 3 BP 572 EP 575 DI 10.1111/j.1530-0277.1992.tb01419.x PG 4 WC Substance Abuse SC Substance Abuse GA HZ911 UT WOS:A1992HZ91100026 PM 1626658 ER PT J AU TERI, L RABINS, P WHITEHOUSE, P BERG, L REISBERG, B SUNDERLAND, T EICHELMAN, B PHELPS, C AF TERI, L RABINS, P WHITEHOUSE, P BERG, L REISBERG, B SUNDERLAND, T EICHELMAN, B PHELPS, C TI MANAGEMENT OF BEHAVIOR DISTURBANCE IN ALZHEIMER-DISEASE - CURRENT KNOWLEDGE AND FUTURE-DIRECTIONS SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Review DE BEHAVIOR DISTURBANCE; COGNITION; DEMENTIA; MANAGEMENT ID AGGRESSIVE-BEHAVIOR; DEMENTIA PATIENTS; NURSING-HOME; DEPRESSION; SYMPTOMS; CAREGIVERS; PREDICTORS; PREVALENCE; RESIDENTS; PSYCHOSIS AB Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition. C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. WASHINGTON UNIV,ST LOUIS,MO 63130. NYU MED CTR,NEW YORK,NY 10016. NIMH,BETHESDA,MD 20892. TEMPLE UNIV,PHILADELPHIA,PA 19122. ALZHEIMERS ASSOC,CHICAGO,IL. RP TERI, L (reprint author), UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,RP-10,SEATTLE,WA 98195, USA. NR 59 TC 86 Z9 88 U1 1 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD SUM PY 1992 VL 6 IS 2 BP 77 EP 88 DI 10.1097/00002093-199206020-00003 PG 12 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA JM239 UT WOS:A1992JM23900003 PM 1389083 ER PT J AU KITTUR, SD ENDO, H ADLER, WH MARTIN, GR MARKESBERY, WR KLEINMAN, HK WEEKS, BS AF KITTUR, SD ENDO, H ADLER, WH MARTIN, GR MARKESBERY, WR KLEINMAN, HK WEEKS, BS TI ALZHEIMER-DISEASE BRAIN EXTRACT STIMULATES BRANCHING OF LAMININ-MEDIATED NEURONAL PROCESSES SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE BRANCHING; NEURONAL PROCESSES; NEUROFIBRILLARY TANGLE ID AMYLOID-BETA-PROTEIN; GROWTH-FACTOR; CORTICAL-NEURONS; DIAGNOSIS; SURVIVAL AB Patients with Alzheimer disease (AD) suffer mental deterioration associated with neurofibrillary tangle and senile plaque formation in the brain. Here we have determined the effects of brain extracts from normal and from AD patients on neuronal process formation by a pheochromocytoma (PC-12) and a neuroblastoma x glioma hybrid cell line (NG108-15). PC12 cells show a dose-related stimulation of branching of neuronal processes by AD brain extracts with cells cultured on a laminin substrate. The neurotrophic effects of extracts of AD brains may be related to the abnormal sprouting and neurofibrillary tangle formation observed in the brain in this disorder. C1 UNIV KENTUCKY,SANDERS BROWN CTR AGING,LEXINGTON,KY 40506. NIDR,BETHESDA,MD 20892. RP KITTUR, SD (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 28 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD SUM PY 1992 VL 6 IS 2 BP 103 EP 110 DI 10.1097/00002093-199206020-00005 PG 8 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA JM239 UT WOS:A1992JM23900005 PM 1389079 ER PT J AU ROBERTS, WC AF ROBERTS, WC TI MORPHOLOGICAL ASPECTS OF CARDIAC-VALVE DYSFUNCTION SO AMERICAN HEART JOURNAL LA English DT Review ID BICUSPID AORTIC-VALVE; SEVERE MITRAL REGURGITATION; OPERATIVELY-EXCISED VALVES; MARFAN-SYNDROME; INFECTIVE ENDOCARDITIS; CARDIOVASCULAR-DISEASE; DISSECTING ANEURYSM; GENERAL-POPULATION; SURGICAL PATHOLOGY; CALCIFIC DEPOSITS RP ROBERTS, WC (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 112 TC 17 Z9 17 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1992 VL 123 IS 6 BP 1610 EP 1632 DI 10.1016/0002-8703(92)90817-F PG 23 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HX943 UT WOS:A1992HX94300026 PM 1595543 ER PT J AU MILEI, J MAUTNER, B STORINO, R SANCHEZ, JA FERRANS, VJ AF MILEI, J MAUTNER, B STORINO, R SANCHEZ, JA FERRANS, VJ TI DOES CHAGAS-DISEASE EXIST AS AN UNDIAGNOSED FORM OF CARDIOMYOPATHY IN THE UNITED-STATES SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID TRYPANOSOMA-CRUZI INFECTION; AMERICAN TRYPANOSOMIASIS; IMMIGRANTS; CALIFORNIA C1 HOSP FERNANDEZ,CTR ENFERMEDAD CHAGAS,DIV CARDIOL,BUENOS AIRES,ARGENTINA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. OI MILEI, JOSE/0000-0003-4029-5993 NR 38 TC 42 Z9 42 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1992 VL 123 IS 6 BP 1732 EP 1735 DI 10.1016/0002-8703(92)90855-P PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HX943 UT WOS:A1992HX94300064 PM 1595572 ER PT J AU MANOLIO, TA BAUGHMAN, KL RODEHEFFER, R PEARSON, TA BRISTOW, JD MICHELS, VV ABELMANN, WH HARLAN, WR AF MANOLIO, TA BAUGHMAN, KL RODEHEFFER, R PEARSON, TA BRISTOW, JD MICHELS, VV ABELMANN, WH HARLAN, WR TI PREVALENCE AND ETIOLOGY OF IDIOPATHIC DILATED CARDIOMYOPATHY (SUMMARY OF A NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE WORKSHOP) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CARDIAC TRANSPLANTATION; ACTIVE MYOCARDITIS; RISK-FACTORS; DOXORUBICIN CARDIOTOXICITY; CONGESTIVE CARDIOMYOPATHY; VASODILATOR THERAPY; BETA-BLOCKADE; FAILURE; MORTALITY AB Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood institute convened a workshop on the Prevalence and Etiology of idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions. C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. MAYO CLIN & MED CTR,DEPT MED GENET,DIV CARDIOVASC DIS,ROCHESTER,MN. COLUMBIA UNIV,MARY IMOGENE BASSETT RES INST,COOPERSTOWN,NY. OREGON HLTH SCI UNIV,DIV CARDIOL,PORTLAND,OR 97201. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN & GENET EPIDEMIOL BRANCH,EBP,BETHESDA,MD 20892, USA. NR 82 TC 279 Z9 293 U1 1 U2 9 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 JUN 1 PY 1992 VL 69 IS 17 BP 1458 EP 1466 DI 10.1016/0002-9149(92)90901-A PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HW170 UT WOS:A1992HW17000017 PM 1590237 ER PT J AU MICOZZI, MS BROWN, ED EDWARDS, BK BIERI, JG TAYLOR, PR KHACHIK, F BEECHER, GR SMITH, JC AF MICOZZI, MS BROWN, ED EDWARDS, BK BIERI, JG TAYLOR, PR KHACHIK, F BEECHER, GR SMITH, JC TI PLASMA CAROTENOID RESPONSE TO CHRONIC INTAKE OF SELECTED FOODS AND BETA-CAROTENE SUPPLEMENTS IN MEN SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE BETA-CAROTENE; CAROTENOIDS; FOODS; LYCOPENE; LUTEIN; ALPHA-CAROTENE; SUPPLEMENTS ID PERFORMANCE LIQUID-CHROMATOGRAPHY; INDIVIDUAL CAROTENOIDS; VITAMIN-A; CANCER; RETINOL; QUANTIFICATION; VEGETABLES; TOCOPHEROL; ANCIENT; REDUCE AB We determined serial changes in four major plasma carotenoid fractions (alpha-carotene, beta-carotene, lutein/zeaxanthin, and lycopene) in 30 men consuming defined daily doses of carotenoids from foods (broccoli, carrots, or tomato juice) or from purified-beta-carotene in capsules (12 or 30 mg) for 6 wk while fed a controlled diet. Compared with baseline, beta-carotene increased in the 30- and 12-mg-capsule and carrot groups whereas alpha-carotene increased in the carrot group and lutein increased in the broccoli group. Lower lutein concentrations in recipients of beta-carotene capsules suggested an interaction between these two carotenoids. Lycopene declined in all groups except the tomato-juice group. Total carotenoid concentration changes only reflected the large increases in beta-carotene concentrations and not the smaller changes observed in other individual carotenoids. Overall, purified-beta-carotene produced a greater plasma response than did similar quantities of carotenoids from foods sources. However, some foods increased plasma concentrations of certain carotenoids. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,NATL MUSEUM HLTH & MED,WASHINGTON,DC 20306. USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. RI Khachik, Frederick/C-5055-2009 NR 28 TC 235 Z9 241 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1992 VL 55 IS 6 BP 1120 EP 1125 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA HX173 UT WOS:A1992HX17300013 PM 1595584 ER PT J AU SIDRANSKY, E GINNS, EI AF SIDRANSKY, E GINNS, EI TI ERYTHROPOIETIN LEVELS IN GAUCHER PATIENTS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID DISEASE RP SIDRANSKY, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892, USA. NR 6 TC 3 Z9 3 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 1992 VL 40 IS 2 BP 153 EP 154 DI 10.1002/ajh.2830400216 PG 2 WC Hematology SC Hematology GA HU705 UT WOS:A1992HU70500015 PM 1585915 ER PT J AU HORAN, MJ MOCKRIN, SC AF HORAN, MJ MOCKRIN, SC TI HETEROGENEITY OF HYPERTENSION SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE HETEROGENEITY; HYPERTENSION; PATHOPHYSIOLOGY; RISK STRATIFICATION; TREATMENT RESPONSES AB Although all forms of hypertension have in common the finding of elevated blood pressure, further examination reveals great heterogeneity. The risk of hypertension is related not only to the level of blood pressure but also to the presence of other risk factors; the prevalence of hypertension is affected by demographic, clinical, and psychologic characteristics; the pathophysiology of hypertension reflects varying participation of salt-sensitivity, the renin-angiotensin system, and other control mechanisms; and treatment responses differ among patients both with regard to the degree of blood pressure lowering by various therapies and the clinical benefit obtained. Knowledge of these heterogeneities at present is useful but only partial. Additional research is needed to improve prediction of hypertension, to enhance stratification of patients by the mechanisms and risk of their hypertension, to refine the matching of specific therapies and treatment goals to the underlying pathophysiology, and to facilitate transfer of evolving information to the clinician. RP HORAN, MJ (reprint author), NHLBI,FED BLDG,ROOM 320,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 1992 VL 5 IS 6 SU S BP S110 EP S113 PN 2 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JA998 UT WOS:A1992JA99800002 PM 1632931 ER PT J AU MCLAUGHLIN, JK MALKER, HSR BLOT, WJ WEINER, JA STONE, BJ ERICSSON, JLE FRAUMENI, JF AF MCLAUGHLIN, JK MALKER, HSR BLOT, WJ WEINER, JA STONE, BJ ERICSSON, JLE FRAUMENI, JF TI RENAL-CELL CANCER AMONG ARCHITECTS AND ALLIED PROFESSIONALS IN SWEDEN SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE LINKED-REGISTRY ANALYSIS; OCCUPATIONAL CANCER; KIDNEY CANCER; CONSTRUCTION; ASBESTOS ID OCCUPATION; MORTALITY AB The Swedish Cancer-Environment Registry was used to evaluate a recent report of a large excess risk of renal cell cancer among architects in Los Angeles. We identified 131 renal cell cancers among male Swedish architects and allied professionals during a 19-year follow-up period (1961-1979). Compared with the Swedish population, there was no significant excess of renal cell cancer among architects and allied professionals (standardized incidence ratio (SIR) = 1.15; 131 cases). Although it was not possible to estimate the risk for architects alone, the SIR was only 1.06 (16 cases) in a subset of professionals employed in architectural and engineering firms. However, a significant increase in risk (SIR = 1.38) was observed in a related group of workers employed as engineers and construction supervisors in the home construction industry. C1 NATL BOARD OCCUPAT SAFETY & HLTH,S-17184 SOLNA,SWEDEN. NATL BOARD HLTH & WELF,STOCKHOLM,SWEDEN. RP MCLAUGHLIN, JK (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 20 TC 6 Z9 6 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1992 VL 21 IS 6 BP 873 EP 876 DI 10.1002/ajim.4700210610 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HV345 UT WOS:A1992HV34500009 PM 1621695 ER PT J AU ZHENG, W MCLAUGHLIN, JK GAO, YT SILVERMAN, DT GAO, RN BLOT, WJ AF ZHENG, W MCLAUGHLIN, JK GAO, YT SILVERMAN, DT GAO, RN BLOT, WJ TI BLADDER-CANCER AND OCCUPATION IN SHANGHAI, 1980-1984 SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE BLADDER CANCER; OCCUPATION; CHINA; PLASTICS AND CHEMICAL WORKERS ID UNITED-STATES; RISKS; BENZIDINE; WOMEN; DYES; MEN AB To investigate occupational determinants of bladder cancer in the urban area of Shanghai, occupation and industry information for 1,219 incident bladder cancer cases diagnosed during the period 1980 to 1984 were compared with 1982 census data on employment. Standardized incidence ratios (SIR) for bladder cancer were estimated for occupation and industry classifications. Significant excess risks were observed for plastic products workers (male: SIR = 432; female: SIR = 368); textile bleachers, dyers, and finishers (male: SIR = 169); metal refining and processing workers (male: SIR = 139; female: SIR = 197); petroleum refining workers (male: SIR = 2152); railway engine drivers and firemen (male: SIR = 683); and workers employed in industries of apparel and other textile products manufacturing (female: SIR = 204); paper processing (male: SIR = 146; female: SIR = 226); organic chemical manufacturing (male: SIR = 186); plastic product manufacturing (male: SIR = 218; female: SIR = 272); and metallurgy (male: SIR = 107; female: SIR = 561). This study indicates that many of the industries and occupations that are responsible for increased risk throughout the world are also associated with occupational bladder cancer in Shanghai. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN-415,BETHESDA,MD 20892. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NR 21 TC 16 Z9 16 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1992 VL 21 IS 6 BP 877 EP 885 DI 10.1002/ajim.4700210611 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HV345 UT WOS:A1992HV34500010 PM 1621696 ER PT J AU STEENLAND, K SILVERMAN, D ZAEBST, D AF STEENLAND, K SILVERMAN, D ZAEBST, D TI EXPOSURE TO DIESEL EXHAUST IN THE TRUCKING INDUSTRY AND POSSIBLE RELATIONSHIPS WITH LUNG-CANCER SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Note DE DIESEL EXPOSURES; TRUCKING; INDUSTRIAL HYGIENE DATA; LUNG CANCER ID WORKERS AB We previously reported that long-term truck drivers and mechanics in the Teamsters Union had higher lung cancer risks than Teamsters outside the trucking industry. We now summarize results from an industrial hygiene survey of current exposures to diesel exhaust in the trucking industry, and relate these to our prior results pertaining to lung cancer risk. C1 NCI,BETHESDA,MD 20892. RP STEENLAND, K (reprint author), NIOSH,MAILSTOP R13,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 9 TC 47 Z9 47 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1992 VL 21 IS 6 BP 887 EP 890 DI 10.1002/ajim.4700210612 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HV345 UT WOS:A1992HV34500011 PM 1621697 ER PT J AU STAUB, JJ ALTHAUS, BU ENGLER, H RYFF, AS TRABUCCO, P MARQUARDT, K BURCKHARDT, D GIRARD, J WEINTRAUB, BD AF STAUB, JJ ALTHAUS, BU ENGLER, H RYFF, AS TRABUCCO, P MARQUARDT, K BURCKHARDT, D GIRARD, J WEINTRAUB, BD TI SPECTRUM OF SUBCLINICAL AND OVERT HYPOTHYROIDISM - EFFECT ON THYROTROPIN, PROLACTIN, AND THYROID RESERVE, AND METABOLIC IMPACT ON PERIPHERAL TARGET TISSUES SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; L-THYROXINE THERAPY; SUB-CLINICAL HYPOTHYROIDISM; AUTOIMMUNE-THYROIDITIS; HYPO-THYROIDISM; TSH RESPONSE; DOUBLE-BLIND; RISK-FACTORS; HORMONE; WOMEN AB PURPOSE: Subclinical hypothyroidism is found in about 7.5% of females and in about 3% of males. It appears to be a risk factor for atherosclerosis and for coronary heart disease and can affect various other target organs. The morbidity and clinical significance of subclinical hypothyroidism are controversial. Therefore, we evaluated the metabolic impact of progressive thyroid failure in patients with various degrees of hypothyroidism compared with control subjects. PATIENTS AND METHODS: We investigated 86 female patients with the whole spectrum of subclinical hypothyroidism (n = 69) and of overt hypothyroidism (n = 17) and 52 euthyroid women as controls. All subjects underwent full medical and endocrine evaluations (including measurements of thyrotropin [TSH], TSH beta- and alpha-subunits, and prolactin before and after oral administration of thyrotropin-releasing hormone [TRH]) as well as lipid profiles and different tests of peripheral thyroid hormone action. All hypothyroid patients were divided into rive categories according to disease severity grades I to III (subclinical hypothyroidism, with normal thyroxine [T4] levels) and grades IV and V (overt hypothyroidism, with diminished T4). RESULTS: In grade I subclinical hypothyroidism (basal TSH below 6 mU/L), we found significant changes in the clinical index (p <0.05), apoprotein A-I level (p <0.05), and stimulated prolactin level after oral TRH (p <0.001). The findings were similar in grade II (TSH 6 to 12 mU/L). Further changes could be demonstrated in grade III (TSH above 12 mU/L) with a definite elevation of ankle reflex time (p <0.001), serum myoglobin level (p <0.01), and, to a lesser extent, creatine kinase (p >0.1). The mean low-density lipoprotein cholesterol (LDL-C) level showed an increase of 18%, which was not significant because of marked individual variations (p = 0.15). The frequency of elevated LDL-C levels was definitely higher in patients with grade III disease compared with the controls (42.9% versus 11.4%, p <0.05) and with patients with grades I and II disease. Total cholesterol, triglycerides, apoprotein B, and the systolic time intervals (pre-ejection period, corrected for heart rate [PEPc]) were clearly elevated only in overt hypothyroidism (grades IV and V) (p <0.01). CONCLUSION: Subclinical hypothyroidism has significant effects on some peripheral target organs at an early stage (grades I and II), but affects LDL-C, skeletal muscle, and myocardial contractility only at a later stage (grades III, IV, and V). Our data of elevated LDL-C in grade III subclinical hypothyroidism provide a likely pathophysiologic explanation for the reported association of coronary heart disease with this syndrome. The impact of increased prolactin secretion, observed in subclinical hypothyroidism, on gonadal function and infertility has yet to be clarified. Therapy with thyroxine should be recommended in at least some patients with subclinical hypothyroidism. Patients with high TSH levels (above 12 mU/L) will require treatment because of the metabolic effects on several target organs. Before treatment is advocated in all patients with subclinical hypothyroidism, the benefits and long-term side effects of thyroid hormone therapy should be clarified by prospective studies in larger groups of patients. C1 UNIV BASEL,CHILDRENS HOSP,DEPT MED,DIV CARDIOL,CH-4031 BASEL,SWITZERLAND. UNIV BASEL,CHILDRENS HOSP,DIV ENDOCRINOL,CH-4031 BASEL,SWITZERLAND. UNIV BASEL,CHILDRENS HOSP,HORMONE LAB,CH-4031 BASEL,SWITZERLAND. NIH,MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP STAUB, JJ (reprint author), UNIV BASEL,CHILDRENS HOSP,DEPT MED,DIV ENDOCRINOL & METAB,CH-4031 BASEL,SWITZERLAND. NR 44 TC 212 Z9 223 U1 1 U2 9 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1992 VL 92 IS 6 BP 631 EP 642 DI 10.1016/0002-9343(92)90782-7 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA HY439 UT WOS:A1992HY43900010 PM 1605145 ER PT J AU ESCHENBACH, DA HILLIER, S NUGENT, RP AF ESCHENBACH, DA HILLIER, S NUGENT, RP TI UREAPLASMA-UREALYTICUM RESISTANCE TO ERYTHROMYCIN - CONFIRMED BY CLINICAL-TRIAL - REPLY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD,BETHESDA,MD 20892. RP ESCHENBACH, DA (reprint author), UNIV WASHINGTON,DEPT OBSTET & GYNECOL,SEATTLE,WA 98195, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 1992 VL 166 IS 6 BP 1864 EP 1865 PN 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JA206 UT WOS:A1992JA20600038 ER PT J AU GREEN, JE BAIRD, AM HINRICHS, SH KLINTWORTH, GK JAY, G AF GREEN, JE BAIRD, AM HINRICHS, SH KLINTWORTH, GK JAY, G TI ADRENAL-MEDULLARY TUMORS AND IRIS PROLIFERATION IN A TRANSGENIC MOUSE MODEL OF NEUROFIBROMATOSIS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; COLONY-STIMULATING FACTOR; INTERLEUKIN-2 RECEPTOR; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; LISCH NODULES; GENE; EXPRESSION; HTLV-1 AB The expression of the human T-cell lymphotropic virus type 1 (HTLV-1) tax gene in transgenic mice has been shown to result in the development of neurofibromas. 1 Further characterization of these transgenic mice bas revealed other significant pathologic similarities between this transgenic mouse model and human neurofibromatosis (NF). Pheochromocytomas of the adrenal medulla and hamartomas of the iris are well-recognized manifestations of human NF. Adrenal medullary tumors have been found in 68% of transgenic animals that were studied. They appear, however, not to be pheochromocytomas, but rather composed of undifferentiated spindle cells. Proliferation of fibroblastlike cells in the iris also occurs in one-half of the transgenic animals surviving more than 6 months. Melanocytes, however, have not been found in the transgenic iris lesion although they are characteristically found in the Lisch nodules of human NF. The similarities between human neurofibromatosis and this transgenic mouse model (in which the overexpression of a single gene results in neoplasia) are discussed This transgenic system may provide further insights into molecular mechanisms involved in the pathogenesis of neurofibromatosis. C1 UNIV CALIF DAVIS,DAVIS,CA 95616. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT OPHTHALMOL,DURHAM,NC 27710. AMER RED CROSS,JEROME H HOLLAND LAB,VIROL LAB,ROCKVILLE,MD. RP GREEN, JE (reprint author), NCI,FCRDC,MOLEC ONCOL LAB,POB B,BLDG 469,ROOM 237,FREDERICK,MD 21702, USA. RI Jay, Gregory/C-6346-2013 FU NCI NIH HHS [CA 496624, CA 51779-01] NR 46 TC 24 Z9 25 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1992 VL 140 IS 6 BP 1401 EP 1410 PG 10 WC Pathology SC Pathology GA HY135 UT WOS:A1992HY13500014 PM 1605307 ER PT J AU FINZI, E BLAKE, MJ CELANO, P SKOUGE, J DIWAN, R AF FINZI, E BLAKE, MJ CELANO, P SKOUGE, J DIWAN, R TI CELLULAR-LOCALIZATION OF RETINOIC ACID RECEPTOR-GAMMA EXPRESSION IN NORMAL AND NEOPLASTIC SKIN SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CYSTIC ACNE; VITAMIN-A; 13-CIS-RETINOIC ACID; LAMELLAR ICHTHYOSIS; CORNIFIED ENVELOPE; MOUSE; DIFFERENTIATION; ISOTRETINOIN; CARCINOMA; KERATINOCYTES AB Retinoids profoundly affect the normal growth and differentiation of epithelial tissues. Retinoic acid receptor-gamma (RAR-gamma) is a member of a family of retinoid receptors, and bas been shown to be expressed almost exclusively in skin However, little is known about the cellular localization of this receptor in human skin. The authors studied the expression of RAR-gamma in normal skin and human skin tumors by Northern blot analysis and in situ hybridization RAR-gamma mRNA was detected in normal skin as well as in cultures of neonatal keratinocytes. Using an oligonucleotide specific for the RAR-gamma cDNA isoform 1 (RAR-gamma-1), RAR-gamma-1 mRNA was localized to all layers of the epidermis the outer root sheath of hair follicles, follicular hair bulbs, eccrine and sebaceous glands. Basal cell carcinoma constitutively expressed gamma-1 mRNA and one of seven squamous cell carcinomas showed loss of gamma-1 mRNA expression, relative to adjacent epithelium. By contrast, normal melanocytic nevi and tumor-associated lymphocytes expressed little or no RAR-gamma mRNA. These results suggest that RAR-gamma-1 may play an important role in the maintenance and differentiation of normal epidermis and skin appendages. C1 JOHNS HOPKINS MED INST,DEPT ONCOL,BALTIMORE,MD 21205. NIA,MOLEC GENET LAB,BETHESDA,MD 20892. RP FINZI, E (reprint author), JOHNS HOPKINS MED INST,DEPT DERMATOL,BLALOCK 920,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 52 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1992 VL 140 IS 6 BP 1463 EP 1471 PG 9 WC Pathology SC Pathology GA HY135 UT WOS:A1992HY13500020 PM 1318641 ER PT J AU PRALONGZAMOFING, D YI, QH SCHMALZING, G GOOD, P GEERING, K AF PRALONGZAMOFING, D YI, QH SCHMALZING, G GOOD, P GEERING, K TI REGULATION OF ALPHA-1-BETA-3-NA+-K+-ATPASE ISOZYME DURING MEIOTIC MATURATION OF XENOPUS-LAEVIS OOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SODIUM-POTASSIUM-ADENOSINE-TRIPHOSPHATASE ISOFORMS; PROGESTERONE-INDUCED OOCYTE MATURATION; XENOPUS EMBRYOS; ENDOCYTOSIS ID NA,K-ATPASE BETA-SUBUNIT; NA+-K+-ATPASE; DOWN-REGULATION; VOLTAGE DEPENDENCE; ALPHA-SUBUNITS; SODIUM PUMPS; MEMBRANE; EXPRESSION; TRANSPORT; CELLS AB During progesterone-induced maturation of Xenopus oocytes, the transport and ouabain binding capacity of Na+-K+-ATPase at the plasma membrane is completely downregulated. To elucidate the mechanism and the physiological significance of this process, we have followed the fate of oocyte alpha-beta-3-Na+-K+-ATPase complexes during meiotic maturation and early embryonic development. An immunocytochemical follow-up of the catalytic alpha-subunit, ouabain binding studies, cell surface iodination, and oocyte cell fractionation combined with immunochemical subunit detection provides evidence that following progesterone treatment Na+ K+-ATPase molecules are retrieved from the oocyte plasma membrane, The enzyme complexes are recovered in an active form in an intracellular compartment in both in vitro and in vivo matured eggs. Exogenous Xenopus alpha-1- and beta-1-complexes expressed in the oocyte from injected cRNAs are regulated by progesterone similar to endogenous Na+-K+-ATPase complexes. Finally, active Na+-K+ pumps internalized during oocyte maturation appear to be redistributed to plasma membrane fractions during blastula formation in Xenopus embryos. In conclusion, our data suggest that endocytosis of alpha-1- and beta-1-complexes during meiotic maturation of Xenopus oocytes is responsible for downregulation of Na+-K+-ATPase activity and results in an intracellular pool of functional enzymes, which might be reexpressed during early development in response to physiological needs. C1 UNIV LAUSANNE,INST PHARMACOL & TOXICOL,RUE BUGNON 27,CH-1005 LAUSANNE,SWITZERLAND. MAX PLANCK INST BIOPHYS,W-6000 FRANKFURT,GERMANY. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 41 TC 19 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1992 VL 262 IS 6 BP C1520 EP C1530 PN 1 PG 11 WC Physiology SC Physiology GA JC376 UT WOS:A1992JC37600025 ER PT J AU LAUGHLIN, MR TAYLOR, JF CHESNICK, AS BALABAN, RS AF LAUGHLIN, MR TAYLOR, JF CHESNICK, AS BALABAN, RS TI REGULATION OF GLYCOGEN-METABOLISM IN CANINE MYOCARDIUM - EFFECTS OF INSULIN AND EPINEPHRINE INVIVO SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GLUCOSE; LACTATE; CARBON-13-NUCLEAR MAGNETIC RESONANCE; MYOCARDIAL METABOLISM; OXYGEN CONSUMPTION ID RAT-HEART; CONSCIOUS DOG; EXERCISE; SYNTHASE; MUSCLE; REPLETION; CATECHOLAMINES; GLUCAGON; GLUCOSE AB Myocardial glycogen synthesis and glucose, lactate, and oxygen extraction were measured in the hearts of anesthetized dogs during infusions of insulin and epinephrine. Glycogen was monitored in vivo using C-13-nuclear magnetic resonance during an infusion of [1-C-13]glucose into the left anterior descending artery. Glycogen synthesis was observed during a venous infusion of insulin (1.8-mu-U . min-1 . kg-1), and this newly synthesized glycogen was neither broken down nor was more glycogen synthesized during a subsequent epinephrine infusion (0.5-mu-g . min-1 . kg-1). During recovery from epinephrine, glycogen synthesis occurred at 2.1 times the rate seen in the control period. Glycogen synthesis was not stimulated in the absence of epinephrine by control infusions of saline. Glucose uptake was increased by insulin during the control period (from 0.09 to 0.39-mu-mol . min-1 . g-1), so that the combined extraction of glucose and lactate exceeded the requirement for oxidizable substrate calculated from oxygen consumption. The "excess" glucose (0.15-mu-mol . min-1 . g wet wt-1) is presumably available for glycogen synthesis. During recovery from epinephrine, lactate uptake was increased over threefold. Because this additional lactate supplies most of the fuel required for oxidation, the excess glucose available for glycogen synthesis during this period was two times that seen before epinephrine (an average of 0.32-mu-mol . min-1 . g wet wt-1 between 20 and 40 min postepinephrine). These data are consistent with the notion that glycogen synthesis can be activated in the heart without an accompanying increase in glucose uptake by providing an alternative substrate (i.e., lactate) for oxidation. RP LAUGHLIN, MR (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 1,RM B307,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 33 TC 33 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1992 VL 262 IS 6 BP E875 EP E883 PN 1 PG 9 WC Physiology SC Physiology GA JC376 UT WOS:A1992JC37600042 PM 1616021 ER PT J AU WALL, SM HAN, JS CHOU, CL KNEPPER, MA AF WALL, SM HAN, JS CHOU, CL KNEPPER, MA TI KINETICS OF UREA AND WATER PERMEABILITY ACTIVATION BY VASOPRESSIN IN RAT TERMINAL IMCD SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE URINARY CONCENTRATION; ISOLATED PERFUSED TUBULE; FLUORESCEIN SULFONATE; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE ID MEDULLARY COLLECTING DUCT; TOAD BLADDER; ANTIDIURETIC-HORMONE; URINARY-BLADDER; TRANSPORT; TUBULE; CELLS; MEMBRANES; PERMEATION; ENDOSOMES AB The vasopressin-regulated urea carrier and the vasopressin-regulated water channel are distinct transporters present in the apical membrane of the inner medullary collecting duct (IMCD) cells. To assess whether these transporters may be activated by common mechanisms, we investigated the time course of increase of urea and water permeability in response to vasopressin in isolated perfused terminal IMCD segments. The permeability responses were determined through the use of a specially designed continuous-flow fluorometer for rapid analysis of collected tubule fluid samples. The time courses of activation of the two transporters by vasopressin were virtually identical. Both urea and water permeability displayed a rapid initial increase for the first 10 min followed by a slower secondary response lasting at least 30 additional min. The lag periods between vasopressin addition and the initial rise in permeability were the same for urea (34.2 +/- 8.8 s) and water (34.8 +/- 8.9 s) transport activation. Furthermore, the initial rate of permeability increase (normalized by the total increase) was not significantly different for the two transport processes. The lag periods for the increase in urea permeability in response to 8-bromoadenosine 3',5'-cyclic monophosphate and vasopressin were not significantly different. The results are consistent with the view that the rate-limiting step in vasopressin-induced activation is the same for both the urea carrier and water channel and may lie at a step beyond generation of adenosine 3',5'-cyclic monophosphate. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,RM6N307,BLDG 10,BETHESDA,MD 20892. NR 39 TC 96 Z9 97 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1992 VL 262 IS 6 BP F989 EP F998 PN 2 PG 10 WC Physiology SC Physiology GA JC377 UT WOS:A1992JC37700090 PM 1320335 ER PT J AU WRIGHT, PA PACKER, RK GARCIAPEREZ, A KNEPPER, MA AF WRIGHT, PA PACKER, RK GARCIAPEREZ, A KNEPPER, MA TI TIME COURSE OF RENAL GLUTAMATE-DEHYDROGENASE INDUCTION DURING NH4CL LOADING IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AMMONIUM EXCRETION; GLUTAMATE DEHYDROGENASE MESSENGER RIBONUCLEIC ACID; METABOLIC ACIDOSIS; AMMONIAGENESIS; ACID-BASE BALANCE ID PHOSPHATE-DEPENDENT GLUTAMINASE; METABOLIC-ACIDOSIS; NUCLEOTIDE-SEQUENCE; KIDNEY; LIVER; CDNA; RECOVERY; NEPHRON; PH AB To study mechanisms involved in renal glutamate dehydrogenase (GDH) regulation in response to systemic acid loading, we have measured blood pH, ammonium excretion, renal GDH mRNA levels, and GDH activity in rats. Acid intake (0.28 M NH4Cl in drinking water for 3 days) increased GDH mRNA levels in the renal cortex, but had no effect in the outer stripe of the outer medulla, inner stripe of the outer medulla, or the inner medulla. Rats were subjected to a step change in acid intake by alkali loading for 3 days (7.2 meq NaHCO3 per day in food slurry) and shifting to acid loading for up to 7 days (7.2 meq NH4Cl in food slurry). Ammonium excretion rose rapidly, increasing by 14-fold in the first 24-h period and 38-fold in the second 24-h period. Cortical GDH mRNA levels were increased relative to alkali-loaded values by 3.7-fold in 24 h, 4.3-fold in 4 days, but only 2.2-fold in 7 days. GDH activity was unchanged after 24 h of acid intake, but was significantly increased after 48 h. We concluded the following: 1) GDH mRNA is present in all regions of the kidney, but levels increase in response to acid loading only in the renal cortex; 2) GDH mRNA levels increase within 1 day after the initiation of acid loading, but the associated increase in functional enzyme activity takes 2 or more days; and 3) the large increases in ammonium excretion that occur in the first day after initiation of acid loading are not dependent on increased GDH activity. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, RM 6N307, BLDG 10, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, DEPT BIOL SCI, WASHINGTON, DC 20052 USA. NR 31 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1992 VL 262 IS 6 BP F999 EP F1006 PN 2 PG 8 WC Physiology SC Physiology GA JC377 UT WOS:A1992JC37700091 PM 1621822 ER PT J AU SOLLOTT, SJ ZIMAN, BD LAKATTA, EG AF SOLLOTT, SJ ZIMAN, BD LAKATTA, EG TI NOVEL TECHNIQUE TO LOAD INDO-1 FREE ACID INTO SINGLE ADULT CARDIAC MYOCYTES TO ASSESS CYTOSOLIC CA2+ SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CYTOSOLIC CALCIUM; MANGANOUS ION ID INTRACELLULAR FREE CALCIUM; RAT VENTRICULAR MYOCYTES; FLUORESCENT DYES; PLASMA-MEMBRANE; HEART-MUSCLE; FURA-2; CELLS; INDICATORS; FLUCTUATIONS; CALIBRATION AB This report introduces a novel method to load indo-1 "free acid" selectively into the cytosol of cardiac myocytes, presumably by diffusion through momentarily permeable gap junction sites during mechanical dissociation after low-Ca2+ collagenase treatment. Calibration of indo-1 fluorescence in these cells has been accomplished after subtracting average autofluorescence (AF) from time-matched non-indo-loaded cells, taking into account apparent changes in cell AF due to indo-1. There is wide variation in the degree of uncertainty of individual intracellular Ca2+ concentration ([Ca2+]i) determinations among cells, related principally to differences in cellular indo-1 content, to nonlinear aspects of the [Ca2+]-to-fluorescence ratio relationship, and to the uncertainty in the AF subtraction. Consequently, a quantitative estimate of uncertainty also may be employed in formulating weighted estimates of cytosolic [Ca2+]i. The following [Ca2+]i values in rat ventricular cells (nM; in 1 mM bathing extracellular Ca2+ concentration, 25-degrees-C) are given as weighted means +/- 95% confidence intervals (unweighted values in parentheses): 138 +/- 5 (136 +/- 6, n = 44) in quiescent cells, 435 +/- 74 (482 +/- 76, n = 43) at the [Ca2+]i-transient peak during 0.5 Hz steady-state stimulation, and 760 +/- 124 (1,027 +/- 250, n = 42) at the [Ca2+]i-transient peak, postrest. Moreover, these peak [Ca2+]i values fall near the steepest portion of the force-Ca2+ curve (from intact cardiac muscle), consistent with sensitive inotropic regulation and maximal contractile reserve. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NR 33 TC 38 Z9 38 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1992 VL 262 IS 6 BP H1941 EP H1949 PN 2 PG 9 WC Physiology SC Physiology GA JC377 UT WOS:A1992JC37700044 ER PT J AU GROSSMAN, E GOLDSTEIN, DS HOFFMAN, A WACKS, IR EPSTEIN, M AF GROSSMAN, E GOLDSTEIN, DS HOFFMAN, A WACKS, IR EPSTEIN, M TI EFFECTS OF WATER IMMERSION ON SYMPATHOADRENAL AND DOPA-DOPAMINE SYSTEMS IN HUMANS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NOREPINEPHRINE; SYMPATHETIC NERVOUS SYSTEM; ATRIAL NATRIURETIC PEPTIDE; BLOOD VOLUME; HOMEOSTASIS ID ATRIAL-NATRIURETIC-FACTOR; VOLUME EXPANSION; URINARY DOPAMINE; DECOMPENSATED CIRRHOSIS; PLASMA-CATECHOLAMINES; CENTRAL HYPERVOLEMIA; SALINE INFUSION; SODIUM; NOREPINEPHRINE; EXCRETION AB Water immersion to the neck increases central blood volume and evokes a marked diuresis and natriuresis. The present study examined simultaneously effects of water immersion on activities of three endogenous systems thought to participate in sodium homeostasis: the sympathetic nervous system, the atrial natriuretic peptide system, and the renal dopa-dopamine system. Hourly urine collections and antecubital venous blood samples were obtained from 10 normal subjects before, during, and after sitting in a water-immersion tank for 3 h; four control subjects were studied while seated without immersion. Urine volume was increased by more than threefold after 1 h of immersion (from 1.2 +/- 0.2 ml/min at baseline to 5.9 +/- 0.7 ml/min, P < 0.001) and peaked during the second hour. Urinary sodium excretion increased by more than twofold (from 103 +/- 17-mu-eq/min at baseline to 196 +/- 36-mu-eq/min at 1 h, P < 0.001) and peaked during the third hour. Plasma levels and urinary excretion of norepinephrine (NE) and epinephrine were suppressed consistently during immersion (P < 0.05). There was a marked, prompt, and sustained increase in plasma levels of immunoreactive atrial natriuretic factor (irANF), from 6.9 +/- 1.9 pg/ml at baseline to 17.3 +/- 4.3 pg/ml at 1 h (P < 0.001). Urinary excretion of dopa, dopamine, and 3,4-dihydroxyphenylglycol, a neuronal metabolite of NE, changed in a triphasic pattern, with decreased excretion during the first hour of immersion (P < 0.01), small but consistent increases during the next 2 h, and decreased excretion, to below baseline, during recovery (P < 0.01 for dopa and dopamine). Excretion rates of all these compounds were unchanged in the seated control subjects. The findings suggest that central hypervolemia inhibits sympathoadrenal outflow, stimulates release of atrial natriuretic peptide into the bloodstream, and produces a multiphasic effect on renal dopa-dopamine system activity. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,RM 5N262,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. UNIV MIAMI,VET AFFAIRS MED CTR,SCH MED,NEPHROL SECT,MIAMI,FL 33125. NR 35 TC 23 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUN PY 1992 VL 262 IS 6 BP R993 EP R999 PN 2 PG 7 WC Physiology SC Physiology GA JC377 UT WOS:A1992JC37700055 PM 1535759 ER PT J AU MANJI, HK AF MANJI, HK TI G-PROTEINS - IMPLICATIONS FOR PSYCHIATRY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID ADENYLATE-CYCLASE ACTIVITY; BETA-ADRENERGIC RECEPTORS; NUCLEOTIDE-BINDING-PROTEINS; TRICYCLIC ANTIDEPRESSANT DESIPRAMINE; PHOSPHOLIPASE-C ACTIVITY; RAT LOCUS COERULEUS; GTP-BINDING; CEREBRAL-CORTEX; ALPHA-SUBUNIT; HETEROLOGOUS DESENSITIZATION AB There is mounting evidence that a family of guanosine triphosphate binding proteins (G proteins) play an obligatory role in the transduction of a vast array of extracellular, receptor-detected signals across cell membranes to intracellular effectors. The author reviews the literature dealing with G protein coupling to second messenger generation, the role of G proteins in regulating both the convergence and divergence of neurotransmitter action in the CNS, and the involvement of G proteins in a variety of clinical conditions, with an emphasis on psychiatric conditions and their treatments. G proteins form the basis of signal integration in the CNS, endowing the neuron with a large degree of functional diversity. Abnormalities in the function and/or expression of G proteins have been implicated in a variety of pathophysiologic states, and a number of currently available psychotropic drugs affect G proteins. The understanding of the mechanisms by which G proteins modulate neuronal activity may be one of the keys to understanding the functioning and the complexities of the nervous system. Given their widespread, critical roles in the regulation of neuronal function, it seems likely that G proteins are involved in the pathophysiology of various major psychiatric illnesses. The development of novel, site-specific drugs with primary G protein targets remains an exciting prospect for the future. RP MANJI, HK (reprint author), NIMH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,BLDG 10,RM 2D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 128 TC 169 Z9 173 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1992 VL 149 IS 6 BP 746 EP 760 PG 15 WC Psychiatry SC Psychiatry GA HW163 UT WOS:A1992HW16300003 PM 1350427 ER PT J AU EGAN, MF HYDE, TM ALBERS, GW ELKASHEF, A ALEXANDER, RC REEVE, A BLUM, A SAENZ, RE WYATT, RJ AF EGAN, MF HYDE, TM ALBERS, GW ELKASHEF, A ALEXANDER, RC REEVE, A BLUM, A SAENZ, RE WYATT, RJ TI TREATMENT OF TARDIVE-DYSKINESIA WITH VITAMIN-E SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 144TH ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOC CY MAY 11-16, 1991 CL NEW ORLEANS, LA SP AMER PSYCHIAT ASSOC ID FREE-RADICALS; 6-HYDROXYDOPAMINE; TOXICITY; DAMAGE; CELLS; SCALE AB Objective: Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group. Method: Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis. Results: Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who bad had tardive dyskinesia for S years or less bad significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment. Conclusions: Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for S years or less. This effect was not due to an increase in blood levels of neuroleptic medications. C1 STANFORD UNIV,MED CTR,SCH MED,MENLO PK & PALO ALTO VET ADM HOSP,STANFORD,CA 94305. RP EGAN, MF (reprint author), NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 28 TC 118 Z9 118 U1 2 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1992 VL 149 IS 6 BP 773 EP 777 PG 5 WC Psychiatry SC Psychiatry GA HW163 UT WOS:A1992HW16300006 PM 1350428 ER PT J AU DREYER, G OTTESEN, EA GALDINO, E ANDRADE, L ROCHA, A MEDEIROS, Z MOURA, I CASIMIRO, I BELIZ, F COUTINHO, A AF DREYER, G OTTESEN, EA GALDINO, E ANDRADE, L ROCHA, A MEDEIROS, Z MOURA, I CASIMIRO, I BELIZ, F COUTINHO, A TI RENAL ABNORMALITIES IN MICROFILAREMIC PATIENTS WITH BANCROFTIAN FILARIASIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID IMMUNE-COMPLEXES; ANTIGEN; ANTIBODY; INFECTION; GLOMERULONEPHRITIS AB To determine the frequency of renal abnormalities occurring with Bancroftian filarial infections and to assess the effects of treatment on such abnormalities, we initiated a prospective, hospital-based study of 20 microfilaremic and five amicrofilaremic patients with Wuchereria bancrofti infections. Thorough clinical evaluations and detailed renal assessments were made prior to treatment and at multiple time points for 60 days following a standard twelve-day course of treatment with diethylcarbamazine (DEC). There were two important findings. First, even prior to DEC treatment, almost half of the microfilaremic patients had hematuria and/or proteinuria. Second, treatment with DEC induced these same abnormalities in almost all of the remaining microfilaremic patients. However, this DEC-induced hematuria and/or proteinuria was transient, and the long-term response to DEC in all of the microfilaremic patients was resolution of the abnormal renal findings during the two-month followup period. In the amicrofilaremic study patients, no hematuria or proteinuria was detected before, during, or after treatment with DEC. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV FED PERNAMBUCO,HOSP CLIN,BR-50000 RECIFE,PE,BRAZIL. RP DREYER, G (reprint author), CTR PESQUISAS AGGEU MAGALHAES,RECIFE,BRAZIL. NR 33 TC 54 Z9 59 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1992 VL 46 IS 6 BP 745 EP 751 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA JD142 UT WOS:A1992JD14200018 PM 1621900 ER PT J AU CHEEVER, AW MACEDONIA, JG ERIK, SD CHEEVER, EA MOSIMANN, JE AF CHEEVER, AW MACEDONIA, JG ERIK, SD CHEEVER, EA MOSIMANN, JE TI PERSISTENCE OF EGGS AND HEPATIC-FIBROSIS AFTER TREATMENT OF SCHISTOSOMA-MANSONI-INFECTED MICE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MURINE SCHISTOSOMIASIS; CHEMOTHERAPY; REVERSAL AB In 1971 we estimated that Schistosoma mansoni eggs in the tissues of mice were destroyed with an approximate half-life of four weeks. Our present results of five experiments suggest that egg destruction is not as rapid, and no significant destruction of eggs was detected for up to 26 weeks after treatment. However, in these experiments, a mean of 60% of the eggs in intestinal tissues were found in the feces at the time of treatment. In previously reported experiments, only 15% of gut eggs were passed in the feces. We now believe that underestimation of the number of eggs passed in the feces led to an overestimation of the number of eggs destroyed in the tissues. We analyzed liver eggs separately because eggs lost from this site are unaffected by eggs passed in the feces. No significant decrease in liver eggs occurred in the present experiments, but reanalysis of previously published data showed significant egg destruction in the liver in several experiments, although at a much slower rate than previously estimated. However, inspection of the data in the previously published and present experiments does not show a convincing difference in the number of eggs in the liver after treatment. The persistence of egg shells is probably not important in the pathogenesis of disease, but is of concern in calculating worm fecundity. Hepatic collagen levels increased markedly two weeks after treatment and subsequently decreased significantly in some, but not all, experiments. C1 NIH,DIV COMP RES & TECHNOL,STAT & MATH METHODOL LAB,BETHESDA,MD 20892. SWARTHMORE COLL,DEPT ENGN,SWARTHMORE,PA 19081. RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 20 TC 11 Z9 12 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1992 VL 46 IS 6 BP 752 EP 758 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA JD142 UT WOS:A1992JD14200019 PM 1320344 ER PT J AU RACE, R ERNST, D JENNY, A TAYLOR, W SUTTON, D CAUGHEY, B AF RACE, R ERNST, D JENNY, A TAYLOR, W SUTTON, D CAUGHEY, B TI DIAGNOSTIC IMPLICATIONS OF DETECTION OF PROTEINASE K-RESISTANT PROTEIN IN SPLEEN, LYMPH-NODES, AND BRAIN OF SHEEP SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID SCRAPIE PRION; INACTIVATION; IRRADIATION; INFECTIVITY; CLEAVAGE; FIBRILS; AGENT AB Brain, spleen, and selected lymph nodes from sheep with clinical signs of scrapie were analyzed for presence of proteinase K-resistant protein (PrP-res). Diagnosis of scrapie on the basis of detection of PrP-res was compared with diagnosis on the basis of histologic evaluation of the brain from clinically affected or exposed sheep. Proteinase K-resistant protein was found in every brain that was histologically positive for scrapie, and in addition, was found in the brain of several clinically positive sheep that were not diagnosed as scrapie-positive by histologic evaluation. Proteinase K-resistant protein was also found in 87% of the spleens and lymph nodes from sheep that had PrP-res detected in brain homogenates. Therefore, analysis of sheep brain, spleen, or lymph nodes for PrP-res provided a diagnostic approach that was superior to histologic examination alone for detection of naturally scrapie agent-infected sheep. C1 USDA,ANIM & PLANT HLTH INSPECT SERV,NATL VET SERV LABS,AMES,IA 50010. USDA,ANIM & PLANT HLTH INSPECT SERV,VET SERV,SCRAPIE INVEST CTR,AMES,IA 50010. RP RACE, R (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LAB,HAMILTON,MT 59480, USA. NR 26 TC 64 Z9 64 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD JUN PY 1992 VL 53 IS 6 BP 883 EP 889 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA HY072 UT WOS:A1992HY07200003 PM 1352664 ER PT J AU SUFFREDINI, AF SHELHAMER, JH NEUMANN, RD BRENNER, M BALTARO, RJ PARRILLO, JE AF SUFFREDINI, AF SHELHAMER, JH NEUMANN, RD BRENNER, M BALTARO, RJ PARRILLO, JE TI PULMONARY AND OXYGEN-TRANSPORT EFFECTS OF INTRAVENOUSLY ADMINISTERED ENDOTOXIN IN NORMAL HUMANS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID TUMOR NECROSIS FACTOR; HEALTHY HUMANS; INJURY; INTERLEUKIN-1; NEUTROPHILS; ACTIVATION; COMPLEMENT; SHOCK AB Little data are available describing the initial changes in pulmonary function and oxygen transport during human endotoxemia. We studied 26 normal humans after intravenously administered endotoxin (4 ng/kg). To evaluate alterations in gas exchange, hemodynamic monitoring was performed in nine subjects given endotoxin and six subjects given saline only. Compared with the control subjects, no changes in gas exchange occurred at 3 h, but after volume loading (mean, 2.2 L saline infused from 3 to 5 h) the Pa(O2) fell (86.1 +/- 2.3 mm Hg, p = 0.042), and the AaPO2 widened (18.5 +/- 1.7 mm Hg, p = 0.005). Oxygen consumption and delivery both increased significantly at 3 h (219 +/- 17 and 1,030 +/- 43 ml/min.min 2) and 5 h (203 +/- 7 and 949 +/- 48 ml/min.min2) (p less-than-or-equal-to 0.035), whereas oxygen extraction fell at 3 h (p = 0.041). Seventeen subjects underwent bronchoalveolar lavage 14 +/- 4 days before and at 1.5 to 3 h (n = 8) or 5 h after (n = 9) the administration of endotoxin. No increase in the total number of cells or percent or absolute number of neutrophils was found at either time point. The rate of clearance of inhaled Tc-99m-diethylenetriamine pentacetate aerosol, a measure of alveolar epithelial permeability, increased in subjects scanned before 3 h (n = 8; p<0.05), whereas no significant changes occurred in subjects scanned 5 h after endotoxin (n = 5) or in control subjects (n = 6). Early inflammatory responses after intravenous administration of endotoxin to normal humans result in alterations in gas exchange and lung permeability. Because these changes occur without an increase in alveolar neutrophils, they may represent an effect of nonalveolar parenchymal neutrophils or they may occur by non-neutrophil-dependent mechanisms. Early responses of oxygen transport variables during endotoxemia include a hyperdynamic cardiovascular state, with increased oxygen consumption, and a normal capacity to utilize oxygen. These changes may represent some of the early alterations in human pulmonary function and oxygen transport that occur at the onset of gram-negative infections. C1 NIH,WARREN MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. NIH,WARREN MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP SUFFREDINI, AF (reprint author), NIH,WARREN MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,7-D-43,CC,BETHESDA,MD 20892, USA. NR 37 TC 45 Z9 45 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JUN PY 1992 VL 145 IS 6 BP 1398 EP 1403 PG 6 WC Respiratory System SC Respiratory System GA HX941 UT WOS:A1992HX94100029 PM 1596009 ER PT J AU CRAPO, J MILLER, FJ MOSSMAN, B PRYOR, WA KILEY, JP AF CRAPO, J MILLER, FJ MOSSMAN, B PRYOR, WA KILEY, JP TI ENVIRONMENTAL LUNG-DISEASES - RELATIONSHIP BETWEEN ACUTE INFLAMMATORY RESPONSES TO AIR-POLLUTANTS AND CHRONIC LUNG-DISEASE SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Editorial Material C1 NHLBI,DIV LUNG DIS,AIRWAYS DIS BRANCH,WESTWOOD BLDG,ROOM 6A15,BETHESDA,MD 20892. NR 0 TC 23 Z9 23 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JUN PY 1992 VL 145 IS 6 BP 1506 EP 1512 PG 7 WC Respiratory System SC Respiratory System GA HX941 UT WOS:A1992HX94100049 PM 1596028 ER PT J AU GERSTEN, DM GABRIEL, O AF GERSTEN, DM GABRIEL, O TI STAINING FOR ENZYMATIC-ACTIVITY AFTER GEL-ELECTROPHORESIS .2. ENZYMES MODIFYING NUCLEIC-ACIDS SO ANALYTICAL BIOCHEMISTRY LA English DT Review ID DNA-POLYMERASE-ALPHA; SODIUM DODECYL-SULFATE; MONKEY KIDNEY-CELLS; POLYACRYLAMIDE-GEL; RAT-LIVER; POLY(ADP-RIBOSE) POLYMERASE; REVERSE-TRANSCRIPTASE; MOLECULAR-WEIGHT; BLOOMS SYNDROME; POLYNUCLEOTIDE PHOSPHORYLASE C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,ROCKVILLE,MD 20850. RP GERSTEN, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PATHOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 96 TC 12 Z9 12 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN PY 1992 VL 203 IS 2 BP 181 EP 186 DI 10.1016/0003-2697(92)90300-V PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA HX741 UT WOS:A1992HX74100001 PM 1384381 ER PT J AU TOYODA, T WOLFFE, AP AF TOYODA, T WOLFFE, AP TI INVITRO TRANSCRIPTION BY RNA POLYMERASE-II IN EXTRACTS OF XENOPUS OOCYTES, EGGS, AND SOMATIC-CELLS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID RIBONUCLEIC-ACID POLYMERASE; DEVELOPMENTAL REGULATION; AMPHIBIAN EGGS; MULTIPLE FORMS; GENE; DNA; EXPRESSION; LAEVIS; INITIATION; ENHANCER C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892. NR 35 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN PY 1992 VL 203 IS 2 BP 340 EP 347 DI 10.1016/0003-2697(92)90322-X PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA HX741 UT WOS:A1992HX74100023 PM 1416031 ER PT J AU GERGEN, PJ TURKELTAUB, PC KRAMER, RA AF GERGEN, PJ TURKELTAUB, PC KRAMER, RA TI AGE OF ONSET IN CHILDHOOD ASTHMA - DATA FROM A NATIONAL COHORT SO ANNALS OF ALLERGY LA English DT Article ID UNITED-STATES; CHANGING PATTERNS; NATURAL-HISTORY; FOLLOW-UP; CHILDREN; PREVALENCE; PROGNOSIS; EXTRACTS; ALLERGY; POLLEN AB There is controversy over the role of age of asthma onset in childhood asthma. Data collected on self-reported physician-diagnosed asthmatic children and young adults aged 6-24 years (N = 352), who participated in the second National Health and Nutritional Examination, 1976-80 (NHANES II), a national sample, were examined to see whether reported age at onset was associated with the future course of the asthma. Three definitions were used for early onset asthma: asthma beginning before the second birthday, before the third birthday, and before the fourth birthday. Late-onset asthma was defined as asthma beginning on or after the second birthday, the third birthday, and the fourth birthday, respectively. Among 6-14 year olds, late-onset asthmatic subjects as compared with early-onset asthmatic subjects using the three definitions reported more allergic rhinitis OR = 3.79 (95% CI 1.53, 9.41), 3.06 (1.33, 7.07), 2.71 (1.18, 6.22), and were more likely to have at least one positive allergen skin test OR = 2.21 (95% CI 1.02, 4.79), 2.90 (1.29, 6.49), 3.41 (1.50, 7.75). Late-onset asthmatic subjects tended to report that their asthma was active, have more problems during the past 12 months with wheezing, and have lower values for predicted FVC and FEV1. No difference was found in reported chronic rhinitis, sinusitis, other allergies, problems within the last 12 months with cough attacks, or during the past 3 years a period of cough and phlegm lasting more than 3 weeks. Among 15-24 year olds, the age of asthma onset was not associated with the factors examined. In this group the association may be obscured by inaccurate recall of asthma onset or no longer be present due to the dominant role of other factors. The role allergy plays among 6-14 year old late-onset asthmatic subjects requires additional investigation. C1 CTR DIS CONTROL,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD. RP GERGEN, PJ (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,SOLAR RM 4A29,BETHESDA,MD 20892, USA. NR 39 TC 16 Z9 17 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD JUN PY 1992 VL 68 IS 6 BP 507 EP 514 PG 8 WC Allergy SC Allergy GA HY076 UT WOS:A1992HY07600009 PM 1610027 ER PT J AU FRICKHOFEN, N ARNOLD, R HERTENSTEIN, B WIESNETH, M YOUNG, NS AF FRICKHOFEN, N ARNOLD, R HERTENSTEIN, B WIESNETH, M YOUNG, NS TI PARVOVIRUS-B19 INFECTION AND BONE-MARROW TRANSPLANTATION SO ANNALS OF HEMATOLOGY LA English DT Article; Proceedings Paper CT SYMP ON BONE MARROW TRANSPLANTATION AND VIRUS INFECTIONS CY MAY 31-JUN 01, 1991 CL TUBINGEN, GERMANY DE PARVOVIRUS-B19; INFECTION; BONE MARROW TRANSPLANTATION; CHRONIC ANEMIA ID RED-CELL APLASIA; B19 PARVOVIRUS; INVITRO; ANTIBODY; ANEMIA; VIRUS; TRANSMISSION; DURATION; HUMANS AB Parvovirus B 19 lytically infects erythroid progenitor cells and thereby causes cessation of erythropoiesis in infected individuals. Anemia develops only if red cell turnover is increased, as in patients with chronic hemolysis (transient aplastic crisis). In addition to transient marrow failure, B 19 can cause chronic anemia and, rarely, pancytopenia in immunodeficient patients who are not able to mount an adequate immune response to clear the virus. Bone marrow transplantation, although causing significant immunosuppression, is rarely complicated by symptomatic B 19 infection. This is probably due to effective passive immunotherapy by immunoglobulin infusions immediately after transplantation and early reconstitution of antibody responses after uncomplicated transplantation. C1 RED CROSS BLOOD TRANSFUS CTR,ULM,GERMANY. NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. RP FRICKHOFEN, N (reprint author), UNIV ULM,DEPT MED 3,ROBERT KOCH STR 8,W-7900 ULM,GERMANY. NR 28 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD JUN PY 1992 VL 64 SU S BP A121 EP A124 DI 10.1007/BF01715363 PG 4 WC Hematology SC Hematology GA JC383 UT WOS:A1992JC38300001 PM 1637889 ER PT J AU SUH, I SHATEN, BJ CUTLER, JA KULLER, LH AF SUH, I SHATEN, BJ CUTLER, JA KULLER, LH TI ALCOHOL-USE AND MORTALITY FROM CORONARY HEART-DISEASE - THE ROLE OF HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE CORONARY DISEASE; ALCOHOL DRINKING; LIPOPROTEINS, HDL CHOLESTEROL; MORTALITY; DOSE-RESPONSE RELATIONSHIP, DRUG ID CARDIOVASCULAR MORTALITY; CONSUMPTION; MEN; SUBFRACTIONS; FRAMINGHAM; DRINKING AB Objective: To study the association between alcohol consumption and death from coronary heart disease and to determine the extent to which the association can be explained by the high-density lipoprotein (HDL) cholesterol level. Design: A cohort study involving men enrolled in the Multiple Risk Factor Intervention Trial (MRFIT). Setting: Community-based study. Participants: Men (n = 11 688) at high risk for developing coronary heart disease but without clinical evidence of it. More than 90% of the men were white, and the average age was 46 years. Five percent of the men abstained from alcohol during the trial, 81% consumed fewer than 21 alcoholic drinks per week, and 14% consumed more than 21 alcoholic drinks per week. Measurements: Average alcohol intake over 7 years was calculated for MRFIT participants who were alive at the end of the trial and who had at least three follow-up records of alcohol consumption. Post-trial mortality during a 3.8-year period was assessed. Results: The adjusted relative risk for death from coronary heart disease for each increase of 7 drinks per week was 0.89 (95% Cl, 0.80 to 1.00), with an apparent dose-response relationship. The average HDL level was associated with the average alcohol intake in a least-squares regression model (beta = -0.0074; P < 0.01). When the average HDL level was included in the proportional hazards model for mortality from coronary heart disease, the absolute value of the coefficient for average drinks per week declined 45%, yielding an adjusted relative risk for each additional 7 drinks per week of 0.94 (Cl, 0.84 to 1.05). Conclusion: In middle-aged men who are light to moderate drinkers, the inverse association between alcohol consumption and death from coronary heart disease can be explained, in large part, by the HDL cholesterol level, which increases with alcohol consumption. However, alcohol consumption cannot be recommended because of the known adverse effects of excess alcohol use. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,COORDINATING CTR BIOMETR RES,2221 UNIV AVE SE,SUITE 200,MINNEAPOLIS,MN 55414. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20814. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15261. FU NHLBI NIH HHS [HC22971] NR 29 TC 252 Z9 253 U1 0 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1992 VL 116 IS 11 BP 881 EP 887 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA HW137 UT WOS:A1992HW13700001 PM 1580443 ER PT J AU DAUNE, GC FARRER, RG DALAKAS, MC QUARLES, RH AF DAUNE, GC FARRER, RG DALAKAS, MC QUARLES, RH TI SENSORY NEUROPATHY ASSOCIATED WITH MONOCLONAL IMMUNOGLOBULIN-M TO GD1B GANGLIOSIDE SO ANNALS OF NEUROLOGY LA English DT Note ID ANTIBODIES AB A 67-year-old woman with a sensory polyneuropathy was shown to have a serum monoclonal immunoglobulin M-lambda antibody with a titer of 1: 10,000 toward GD1b ganglioside. The immunoglobulin M also reacted with some other gangliosides containing disialosyl groups such as GD2, GD3, and GQ1b, but it did not react with GM 1, LM1, or GD1a. The principal reactive ganglioside in human cauda equina was GD1b. C1 NINCDS, MOLEC & CELLULAR NEUROBIOL LAB, MYELIN & BRAIN DEV SECT, PK BLDG, BETHESDA, MD 20892 USA. NINCDS, MED NEUROL BRANCH, NEUROMUSCULAR DIS SECT, BETHESDA, MD 20892 USA. NR 9 TC 59 Z9 60 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1992 VL 31 IS 6 BP 683 EP 685 DI 10.1002/ana.410310621 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HY141 UT WOS:A1992HY14100020 PM 1381168 ER PT J AU PASS, HI POGREBNIAK, HW STEINBERG, SM MULSHINE, J MINNA, J AF PASS, HI POGREBNIAK, HW STEINBERG, SM MULSHINE, J MINNA, J TI RANDOMIZED TRIAL OF NEOADJUVANT THERAPY FOR LUNG-CANCER - INTERIM ANALYSIS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 38TH ANNUAL MEETING OF THE SOUTHERN THORACIC SURGICAL ASSOC CY NOV 07-09, 1991 CL ORLANDO, FL SP SOC THORAC SURGEONS ID CARCINOMA; CISPLATIN AB The role of neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer remains undefined. Since 1987, 27 patients with non-small cell lung cancer, all with histologically confirmed metastases to the ipsilateral mediastinal lymph nodes, have been enrolled in an ongoing prospective, randomized trial at our institution. Thirteen patients have been randomized to preoperative etoposide-platinum (EP) chemotherapy-surgery-postoperative EP, and 14 other patients have been randomized to surgery-postoperative mediastinal irradiation (SRT). Both groups are similar in sex, age, weight loss, tumor location, preoperative pulmonary function, physiologic grade, and tumor histology. Eight of the 13 EP patients have responded as evidenced by a 50% or greater radiographic tumor shrinkage after two cycles. Complete tumor and nodal resection rates were similar: 11/13 EP patients versus 12/14 SRT patients. There was no operative mortality for the 27 patients. Median potential follow-up is 29.9 months for the EP group and 34.9 months for the SRT group. Preliminary results suggest a trend toward increased survival time for the EP group (median, 28.7 months) versus the SRT group (median, 15.6 months) (p2 = 0.095). Eleven of 12 resected SRT patients have had recurrence versus 8 of 11 resected EP patients. Time to recurrence reveals no significant differences between the two groups but a trend toward increased disease-free interval in the EP group (12.7 months versus 5.8 months, EP versus SRT). This interim analysis demonstrates the feasibility of such a trial; however, despite the trends, definitive conclusions await further accrual and study maturation. RP PASS, HI (reprint author), NCI,THORAC ONCOL SECT,SURG BRANCH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 12 TC 240 Z9 242 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1992 VL 53 IS 6 BP 992 EP 998 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA HX177 UT WOS:A1992HX17700009 PM 1317697 ER PT J AU JAROSZEWSKI, JW SYI, JL MAIZEL, J COHEN, JS AF JAROSZEWSKI, JW SYI, JL MAIZEL, J COHEN, JS TI TOWARDS RATIONAL DESIGN OF ANTISENSE DNA - MOLECULAR MODELING OF PHOSPHOROTHIOATE DNA ANALOGS SO ANTI-CANCER DRUG DESIGN LA English DT Article DE ANTISENSE DNA; PHOSPHOROTHIOATE ISOMERS; MOLECULAR MODELING ID NUCLEIC-ACIDS; STEREOSELECTIVE SYNTHESIS; CRYSTAL-STRUCTURE; FORCE-FIELD; BOND ORDER; B-DNA; PHOSPHORUS; METHANEPHOSPHONATES); DYNAMICS; PROTEINS AB In order to assess the effects of substitution of one of the non-bridging oxygens in the phosphodiester group with sulfur, molecular dynamics calculations were performed on duplex oligodeoxynucleotides having a complete helical turn, {d(CpGpCpGpApApTpTpCpGpCpG)}2. The calculations were carried out with the unmodified duplex, as well as with duplexes having one phosphorothioate strand with uniform phosphorus stereochemistry (S(P) or R(P)). The electrostatic and structural (equilibrium molecular dimensions as well as force constants) parameters of the phosphorothioate group for molecular mechanics and dynamics calculations were derived from ab initio quantum mechanics optimizations of conformers of O,O'-dimethyl phosphorothioate. Molecular dynamics simulations (30 ps) were carried out using the AMBER force field, with explicit inclusion of all hydrogen atoms, counterions, and water. The simulations indicate a significant decrease of stability of the model containing the homochiral R(P)-phosphorothioate strand, whereas the model containing the homochiral S(P)-phosphorothioate strand has practically the same energy as the unmodified oligodeoxynucleotide duplex. The energy difference determined indicates some preference for the use of stereochemically pure S(P)-phosphorothioates as antisense gene inhibitors. Moreover, the significance of these results in connection with use of phosphorodithioates is discussed. C1 ROYAL DANISH SCH PHARM,PHARMABIOTEC RES CTR,DK-2100 COPENHAGEN,DENMARK. FREDERICK CANC RES & DEV CTR,ADV SCI COMP LAB,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCE INC DYNCORP,FREDERICK,MD 21701. NCI,MATH BIOL LAB,FREDERICK,MD 21701. GEORGETOWN UNIV,MED CTR,ROCKVILLE,MD 20850. RP JAROSZEWSKI, JW (reprint author), ROYAL DANISH SCH PHARM,DEPT ORGAN CHEM,UNIV PK 2,DK-2100 COPENHAGEN,DENMARK. FU NCI NIH HHS [N01-CO-74012] NR 28 TC 24 Z9 24 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD JUN PY 1992 VL 7 IS 3 BP 253 EP 262 PG 10 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA JA505 UT WOS:A1992JA50500005 PM 1610482 ER PT J AU HAMEL, E LIN, CM KENNEY, S SKEHAN, P VAUGHNS, J AF HAMEL, E LIN, CM KENNEY, S SKEHAN, P VAUGHNS, J TI MODULATION OF TUBULIN-NUCLEOTIDE INTERACTIONS BY METAL-IONS - COMPARISON OF BERYLLIUM WITH MAGNESIUM AND INITIAL STUDIES WITH OTHER CATIONS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; GUANOSINE 5'-TRIPHOSPHATE HYDROLYSIS; GTP HYDROLYSIS; GUANINE-NUCLEOTIDE; BINDING-SITE; CHROMIUM(III)-NUCLEOTIDE COMPLEXES; DIVALENT-CATIONS; BRAIN TUBULIN; ALUMINUM ION; POLYMERIZATION C1 NCI, F44K-CW00J-RR84FFREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BETHESDA,MD 20892. RP HAMEL, E (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 65 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1992 VL 295 IS 2 BP 327 EP 339 DI 10.1016/0003-9861(92)90525-2 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HU937 UT WOS:A1992HU93700017 PM 1586162 ER PT J AU KRUESI, MJP HIBBS, ED ZAHN, TP KEYSOR, CS HAMBURGER, SD BARTKO, JJ RAPOPORT, JL AF KRUESI, MJP HIBBS, ED ZAHN, TP KEYSOR, CS HAMBURGER, SD BARTKO, JJ RAPOPORT, JL TI A 2-YEAR PROSPECTIVE FOLLOW-UP-STUDY OF CHILDREN AND ADOLESCENTS WITH DISRUPTIVE BEHAVIOR DISORDERS - PREDICTION BY CEREBROSPINAL-FLUID 5-HYDROXYINDOLEACETIC ACID, HOMOVANILLIC-ACID, AND AUTONOMIC MEASURES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MONOAMINE METABOLITES; HYPERACTIVE-CHILDREN; DIAGNOSTIC-INTERVIEW; ANTISOCIAL-BEHAVIOR; AGGRESSIVE-BEHAVIOR; PSYCHIATRIC STATUS; SUICIDAL-BEHAVIOR; CONDUCT DISORDER; CHILDHOOD; SCHIZOPHRENIA AB A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted. C1 NIMH,DIV APPL & SERV RES,BETHESDA,MD 20892. NIMH,CHILD PSYCHIAT BRANCH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,BETHESDA,MD 20892. NR 62 TC 175 Z9 175 U1 3 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1992 VL 49 IS 6 BP 429 EP 435 PG 7 WC Psychiatry SC Psychiatry GA HX957 UT WOS:A1992HX95700001 PM 1376104 ER PT J AU HIGLEY, JD MEHLMAN, PT TAUB, DM HIGLEY, SB SUOMI, SJ LINNOILA, M VICKERS, JH AF HIGLEY, JD MEHLMAN, PT TAUB, DM HIGLEY, SB SUOMI, SJ LINNOILA, M VICKERS, JH TI CEREBROSPINAL-FLUID MONOAMINE AND ADRENAL CORRELATES OF AGGRESSION IN FREE-RANGING RHESUS-MONKEYS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CERCOPITHECUS-AETHIOPS-SABAEUS; VERVET MONKEYS; 5-HYDROXYINDOLEACETIC ACID; AMINE METABOLITES; HOMOVANILLIC-ACID; PLASMA-CORTISOL; MACACA-MULATTA; BEHAVIOR; TESTOSTERONE; TRYPTOPHAN AB Clinical and preclinical studies involving several different mammalian species and research paradigms suggest a negative correlation between aggression and central serotonin activity. To test the generalizability of laboratory findings in rhesus monkeys that show a negative correlation between cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and aggression, we obtained cisternal cerebrospinal fluid and blood plasma samples from monkeys living in naturalistic conditions. During a semiannual trapping 28 juvenile and adolescent male rhesus monkeys were chosen from a population of 4200 provisioned, free-ranging rhesus monkeys living on Morgan Island, a sea island located off the coast of South Carolina. Based on direct observations of participation or avoidance of aggressive behavior and examinations of apparent fight wounds, 18 monkeys were selected for cerebrospinal fluid taps and blood samples. The remaining 10 monkeys were selected at random. Descriptions of aggressive behavior and the number of old scars and recent wounds were carefully transcribed, and a photograph showing wounds and scars was obtained for each animal. Using the transcriptions and photographs, researchers experienced in rhesus monkey behavior, but blind to the subjects' monoamine and hormone concentrations, were asked to rank the monkeys from the most to the least aggressive. The results showed a significant negative correlation between high rankings for aggression and cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. There was evidence that aggression was associated with stress, in that cerebrospinal fluid, norepinephrine, and plasma corticotropin and cortisol concentrations were positively correlated with high rankings of aggression. C1 NIAAA,DIV INTRAMURAL & CLIN BIOL RES,CLIN STUDIES LAB,NEUROCHEM & NEUROENDOCRINOL SECT,BETHESDA,MD. LAB ANIM BREEDERS & SERV,YEMASSEE,SC. US FDA,CTR BIOL EVALUAT & RES,OFF BIOL PROD REVIEW,BETHESDA,MD 20205. NICHHD,CTR ANIM HLTH,COMPARAT ETHOL LAB,BETHESDA,MD 20892. NR 45 TC 232 Z9 233 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1992 VL 49 IS 6 BP 436 EP 441 PG 6 WC Psychiatry SC Psychiatry GA HX957 UT WOS:A1992HX95700002 PM 1376105 ER PT J AU MANN, JJ MCBRIDE, PA BROWN, RP LINNOILA, M LEON, AC DEMEO, M MIECZKOWSKI, T MYERS, JE STANLEY, M AF MANN, JJ MCBRIDE, PA BROWN, RP LINNOILA, M LEON, AC DEMEO, M MIECZKOWSKI, T MYERS, JE STANLEY, M TI RELATIONSHIP BETWEEN CENTRAL AND PERIPHERAL SEROTONIN INDEXES IN DEPRESSED AND SUICIDAL PSYCHIATRIC-INPATIENTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID; RESPONSIVITY; FENFLURAMINE; METABOLITES; ADULTS; BRAIN AB Serious suicidal behavior, affective disorders, and a variety of other psychopathologic behaviors and syndromes have been found to correlate with measures of the serotonin system. Clinical studies have employed a range of serotonin indexes, including the cerebrospinal fluid level of 5-hydroxyindoleacetic acid, the prolactin response to serotonin agonists, such as fenfluramine hydrochloride, and platelet serotonin-related proteins or serotonin content. Many of these indexes are correlated with suicidal behavior, but the interrelationship of these biologic measures has been uncertain. We studied the relationship of a series of serotonin indexes in patients in whom these measures were correlated with suicidal behavior. A positive correlation was found between cerebrospinal fluid 5-hydroxyindoleacetic acid and the maximal prolactin response to fenfluramine but not with platelet serotonin2 receptor indexes. The fenfluramine-stimulated maximal prolactin response correlated with platelet serotonin2 receptor number, particularly in older patients. We conclude that cerebrospinal fluid 5-hydroxyindoleacetic acid measurements cannot be replaced but can be complemented by less invasive procedures, such as a fenfluramine challenge test or platelet serotonin2 measures, in the study of the relationship of the serotonin system to psychiatric disorders. C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD. CORNELL UNIV,MED CTR,COLL MED,DEPT PSYCHIAT,NEW YORK,NY 10021. COLUMBIA UNIV COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. RP MANN, JJ (reprint author), UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,SCH MED,DEPT PSYCHIAT,NEUROPHARMACOL LABS,PITTSBURGH,PA 15213, USA. FU NIMH NIH HHS [IP50-MH46745, MH-41847] NR 26 TC 193 Z9 195 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1992 VL 49 IS 6 BP 442 EP 446 PG 5 WC Psychiatry SC Psychiatry GA HX957 UT WOS:A1992HX95700003 PM 1376106 ER PT J AU ROY, A KAROUM, F POLLACK, S AF ROY, A KAROUM, F POLLACK, S TI MARKED REDUCTION IN INDEXES OF DOPAMINE METABOLISM AMONG PATIENTS WITH DEPRESSION WHO ATTEMPT SUICIDE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MONOAMINE METABOLITES; HOMOVANILLIC-ACID; BEHAVIOR; BRAIN; CSF; MONKEYS; OUTPUT; MHPG; MPTP; HVA AB Cerebrospinal fluid studies have reported that low concentrations of the dopamine metabolite homovanillic acid are associated with suicidal behavior in depression. Although only a small proportion of homovanillic acid in the urine derives from the brain, we decided to examine 24-hour urinary outputs of homovanillic acid in relation to suicidal behavior in depression. Patients with depression who had attempted suicide had significantly smaller urinary outputs of homovanillic acid, dihydroxyphenylacetic acid, and total body output of dopamine (sum dopamine) than did patients with depression who had not attempted suicide. Patients with depression who reattempted suicide during 5-year follow-up had significantly smaller urinary outputs of homovanillic acid and sum dopamine than did patients who did not reattempt suicide, patients who never attempted suicide, and normal control subjects, and had significantly smaller outputs of dihydroxyphenylacetic acid than patients who never attempted suicide or control subjects. These data suggest that urinary outputs of homovanillic acid may be peripheral correlates of suicidality in depression. These data add to data on the low levels of homovanillic acid in cerebrospinal fluid in suggesting that diminished dopaminergic neurotransmission may play a part in suicidal behavior in depression. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. ST JOHNS UNIV,DEPT QUANTITAT ANAL,JAMAICA,NY 11439. RP ROY, A (reprint author), HILLSIDE HOSP,POB 38,GLEN OAKS,NY 11004, USA. NR 26 TC 66 Z9 67 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1992 VL 49 IS 6 BP 447 EP 450 PG 4 WC Psychiatry SC Psychiatry GA HX957 UT WOS:A1992HX95700004 PM 1376107 ER PT J AU BROMFIELD, EB ALTSHULER, L LEIDERMAN, DB BALISH, M KETTER, TA DEVINSKY, O POST, RM THEODORE, WH AF BROMFIELD, EB ALTSHULER, L LEIDERMAN, DB BALISH, M KETTER, TA DEVINSKY, O POST, RM THEODORE, WH TI CEREBRAL METABOLISM AND DEPRESSION IN PATIENTS WITH COMPLEX PARTIAL SEIZURES SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; TEMPORAL-LOBE EPILEPSY; REPRODUCTIVE ENDOCRINE DISORDERS; BRAIN GLUCOSE-METABOLISM; CHRONIC-SCHIZOPHRENIA; PARKINSONS-DISEASE; MOOD DISORDERS; ORIGIN; PHENOMENOLOGY; INVENTORY AB Twenty-three patients with complex partial seizures were evaluated with F-18-2-deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions. C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 61 TC 139 Z9 143 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 1992 VL 49 IS 6 BP 617 EP 623 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA HX958 UT WOS:A1992HX95800008 PM 1596197 ER PT J AU AZEN, SP BARLOW, W BOONE, DC QUILLENTHOMAS, B CHEN, A LEE, MB LINTON, KLP LAI, MY LEE, K BOCHYNSKI, E COX, MS BLUMENKRANZ, MS MARGHERIO, RR MURPHY, PL TRESE, MT WILLIAMS, GA WITKOP, C MANATREY, P LICHTERMAN, S CUMMING, K MCCURLEY, S SNYDER, V COX, S BRIDGES, G JOHNSON, J SOBEL, J STREASICK, P VALENZUELA, CL FLYNN, H BLANKENSHIP, GW CLARKSON, J OLSEN, K VANDENBROUCKE, R ROBEY, M ESPINAL, M ATTAWAY, J BUZNEGO, A CARRICO, D DENBESTE, B EUGENIDES, J LEMKIN, P KIPPENBROCK, R MCCLINTOCH, M NODA, N OLIVA, O PHILLIPS, B HESS, D DURIA, E MCCUEN, BW ANDERSON, B DEJUAN, E JAFFE, GJ MACHEMER, R STEFANSSON, E TIEDEMAN, JS ANDERSON, MM SCHIRMER, R BENETZ, BA AABERG, TM MEREDITH, TA KAPLAN, HJ STERNBERG, P CURTIS, L BOYLES, D MOORE, K LASALLE, J GILMAN, J MAIO, M SWORDS, R FREEMAN, HM TOLENTINO, FI DORRIEN, K BUSBY, A RAPP, E ANDERSON, S FRIEDMAN, G IMMERMAN, R MORANDI, T ODAY, T ROSENBLUM, A GLASER, BM DEBUSTROS, S MICHELS, R ALFORD, A HUPP, J NUNEZ, MA GEORGE, T BURTON, T HAN, DA MIELER, WF REKOW, S PRESCOTT, A RICHIE, MN WIPPLINGER, W KREIGER, A DIDDIE, KR SIDIKARO, J YOSHIZUMI, M EURE, J ARMSTRONG, P KILBURN, D MARK, B PETRUS, R WELLS, P GREENSPAN, J THAYER, D STERN, WH IRVINE, AR STONE, RD BALLESTEROS, F MORRIS, B NARAHARA, M WANNER, M LEAN, JS LIGGETT, PE RYAN, SJ WALONKER, AF HOWARD, E CLARK, T DELGADO, S NICHOLS, T ROZIER, MR TETREAULT, G FEDERMAN, JL FISCHER, D SARIN, LK TASMAN, WS REBER, R NICHOL, J HUTTON, WL FULLER, DG JOST, B SNYDER, WR SPENCER, WB VAISER, A ANDERSON, T POWELL, D DALRYMPLE, D NORK, C AGUADO, H EVANS, R BARR, CC ISERNHAGEN, RA JAEGERS, K RADTKE, ND WOOD, WJ WAGNER, F WHITTINGTON, GK CARPENTER, M COONS, K GILKEY, LA ROGERS, C SAUER, L HUELSMAN, S SLADE, E RAMSAY, RC CANTRILL, HL KNOBLOCK, WH RYAN, EH COOK, S MCDONOUGH, G MONAHAN, M PHILIP, D PONWITH, L STINSON, L ANDERSON, K OESTREICH, N MCMICHAEL, B VAGSTAD, G IRVINE, A HILTON, G LONN, L SCHWARTZ, A HOFFMAN, J HILLIS, A AFIFI, AA FINKELSTEIN, D MCLEAN, EB RUDISILL, AS WILKINSON, CP ABRAMS, GW DAVIS, MD MOWERY, R DUDLEY, P GOLDBERG, I MCLAUGHLIN, J RATHJEN, A HUBBARD, L AF AZEN, SP BARLOW, W BOONE, DC QUILLENTHOMAS, B CHEN, A LEE, MB LINTON, KLP LAI, MY LEE, K BOCHYNSKI, E COX, MS BLUMENKRANZ, MS MARGHERIO, RR MURPHY, PL TRESE, MT WILLIAMS, GA WITKOP, C MANATREY, P LICHTERMAN, S CUMMING, K MCCURLEY, S SNYDER, V COX, S BRIDGES, G JOHNSON, J SOBEL, J STREASICK, P VALENZUELA, CL FLYNN, H BLANKENSHIP, GW CLARKSON, J OLSEN, K VANDENBROUCKE, R ROBEY, M ESPINAL, M ATTAWAY, J BUZNEGO, A CARRICO, D DENBESTE, B EUGENIDES, J LEMKIN, P KIPPENBROCK, R MCCLINTOCH, M NODA, N OLIVA, O PHILLIPS, B HESS, D DURIA, E MCCUEN, BW ANDERSON, B DEJUAN, E JAFFE, GJ MACHEMER, R STEFANSSON, E TIEDEMAN, JS ANDERSON, MM SCHIRMER, R BENETZ, BA AABERG, TM MEREDITH, TA KAPLAN, HJ STERNBERG, P CURTIS, L BOYLES, D MOORE, K LASALLE, J GILMAN, J MAIO, M SWORDS, R FREEMAN, HM TOLENTINO, FI DORRIEN, K BUSBY, A RAPP, E ANDERSON, S FRIEDMAN, G IMMERMAN, R MORANDI, T ODAY, T ROSENBLUM, A GLASER, BM DEBUSTROS, S MICHELS, R ALFORD, A HUPP, J NUNEZ, MA GEORGE, T BURTON, T HAN, DA MIELER, WF REKOW, S PRESCOTT, A RICHIE, MN WIPPLINGER, W KREIGER, A DIDDIE, KR SIDIKARO, J YOSHIZUMI, M EURE, J ARMSTRONG, P KILBURN, D MARK, B PETRUS, R WELLS, P GREENSPAN, J THAYER, D STERN, WH IRVINE, AR STONE, RD BALLESTEROS, F MORRIS, B NARAHARA, M WANNER, M LEAN, JS LIGGETT, PE RYAN, SJ WALONKER, AF HOWARD, E CLARK, T DELGADO, S NICHOLS, T ROZIER, MR TETREAULT, G FEDERMAN, JL FISCHER, D SARIN, LK TASMAN, WS REBER, R NICHOL, J HUTTON, WL FULLER, DG JOST, B SNYDER, WR SPENCER, WB VAISER, A ANDERSON, T POWELL, D DALRYMPLE, D NORK, C AGUADO, H EVANS, R BARR, CC ISERNHAGEN, RA JAEGERS, K RADTKE, ND WOOD, WJ WAGNER, F WHITTINGTON, GK CARPENTER, M COONS, K GILKEY, LA ROGERS, C SAUER, L HUELSMAN, S SLADE, E RAMSAY, RC CANTRILL, HL KNOBLOCK, WH RYAN, EH COOK, S MCDONOUGH, G MONAHAN, M PHILIP, D PONWITH, L STINSON, L ANDERSON, K OESTREICH, N MCMICHAEL, B VAGSTAD, G IRVINE, A HILTON, G LONN, L SCHWARTZ, A HOFFMAN, J HILLIS, A AFIFI, AA FINKELSTEIN, D MCLEAN, EB RUDISILL, AS WILKINSON, CP ABRAMS, GW DAVIS, MD MOWERY, R DUDLEY, P GOLDBERG, I MCLAUGHLIN, J RATHJEN, A HUBBARD, L TI VITRECTOMY WITH SILICONE OIL OR SULFUR-HEXAFLUORIDE GAS IN EYES WITH SEVERE PROLIFERATIVE VITREORETINOPATHY - RESULTS OF A RANDOMIZED CLINICAL-TRIAL - SILICONE STUDY REPORT .1. SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID COMPLICATIONS; SURGERY AB Between September 1985 and September 1987, 101 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy but without prior vitrectomy were treated with vitrectomy and randomized to either a mixture of 20% sulfur hexafluoride gas and air or to 1 000 centistokes of silicone oil. Between 50% and 60% of eyes that received silicone oil had visual acuity better than or equal to 5/200 compared with 30% to 40% of the eyes that received sulfur hexafluoride gas (P<.05). Macula attachment was more frequent in eyes that received silicone oil than in those that received sulfur hexafluoride gas (80% vs 60%, P<.05). Hypotony was more prevalent in eyes with a detached macula (40% to 50% for sulfur hexafluoride gas vs 25% to 30% for silicone oil) when compared with those with attached maculas (<5% for either modality). Keratopathy was more prevalent in eyes with detached maculas (about 55% to 60% for either modality) compared with eyes with attached maculas (25% to 30% for sulfur hexafluoride gas vs 10% to 15% for silicone oil). In a companion article, we show that these differences between a gas tamponade and silicone oil are not found for perfluoropropane gas. C1 UNIV SO CALIF, CTR COORDINATING, LOS ANGELES, CA 90089 USA. ASSOCIATED RETINAL CONSULTANTS, ROYAL OAK, MI USA. UNIV MIAMI, SCH MED, BASCOM PALMER EYE INST, MIAMI, FL 33152 USA. DUKE UNIV, MED CTR, DURHAM, NC 27710 USA. EMORY UNIV, SCH MED, ATLANTA, GA 30322 USA. RETINA ASSOCIATES, BOSTON, MA USA. JOHNS HOPKINS UNIV HOSP, WILMER OPHTHALMOL INST, BALTIMORE, MD 21205 USA. MED COLL WISCONSIN, INST EYE, MILWAUKEE, WI 53226 USA. UNIV CALIF LOS ANGELES, JULES STEIN EYE INST, LOS ANGELES, CA 90024 USA. UNIV CALIF SAN FRANCISCO, SCH MED, SAN FRANCISCO, CA 94143 USA. UNIV SO CALIF, DOHENY EYE INST, LOS ANGELES, CA 90089 USA. WILLS EYE HOSP & RES INST, PHILADELPHIA, PA 19107 USA. TEXAS RETINA ASSOCIATES, DALLAS, TX USA. KENTUCKY RETINA GRP, LOUISVILLE, KY USA. KENTUCKY RETINA GRP, LEXINGTON, KY USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV CALIF SAN FRANCISCO, CTR FUNDUS PHOTOG READING, SAN FRANCISCO, CA 94143 USA. NEI, BETHESDA, MD 20892 USA. UNIV WISCONSIN, CTR FUNDUS PHOTOG READING, MADISON, WI 53706 USA. DOW CORNING CORP, SERV MED RES, MIDLAND, MI 48640 USA. RP AZEN, SP (reprint author), UNIV SO CALIF, SCH MED,DEPT PREVENT MED,DIV BIOMETRY, 1420 SAN PABLO AVE, PMB B101, LOS ANGELES, CA 90033 USA. NR 14 TC 113 Z9 119 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1992 VL 110 IS 6 BP 770 EP 779 PG 10 WC Ophthalmology SC Ophthalmology GA HX947 UT WOS:A1992HX94700016 ER PT J AU AZEN, SP BARLOW, W BOONE, DC QUILLENTHOMAS, B CHEN, A LEE, MB LINTON, KLP LAI, MY LEE, K BOCHYNSKI, E LUNSFORD, M COX, MS BLUMENKRANZ, MS MARGHERIO, RR MURPHY, PL TRESE, MT WILLIAMS, GA WITKOP, C MANATREY, P LICHTERMAN, S CUMMING, K MCCURLEY, S SNYDER, V COX, S BRIDGES, G JOHNSON, J SOBEL, J STREASICK, P VALENZUELA, CL FLYNN, H BLANKENSHIP, GW CLARKSON, J OLSEN, K VANDENBROUCKE, R ROBEY, M ESPINAL, M ATTAWAY, J BUZNEGO, A CARRICO, D DENBESTE, B EUGENIDES, J LEMKIN, P KIPPENBROCK, R MCCLINTOCH, M NODA, N OLIVA, O PHILLIPS, B HESS, D DURIA, E MCCUEN, BW ANDERSON, B DEJUAN, E JAFFE, GJ MACHEMER, R STEFANSSON, E TIEDEMAN, JS ANDERSON, MM SCHIRMER, R BENETZ, BA AABERG, TM MEREDITH, TA KAPLAN, HJ STERNBERG, P CURTIS, L BOYLES, D MOORE, K LASALLE, J GILMAN, J MAIO, M SWORDS, R FREEMAN, HM TOLENTINO, FI DORRIEN, K BUSBY, A RAPP, E ANDERSON, S FRIEDMAN, G IMMERMAN, R MORANDI, T ODAY, T ROSENBLUM, A GLASER, BM DEBUSTROS, S MICHELS, R ALFORD, A HUPP, J NUNEZ, MA GEORGE, T BURTON, T HAN, DA MIELER, WF REKOW, S PRESCOTT, A RICHIE, MN WIPPLINGER, W KREIGER, A DIDDIE, KR SIDIKARO, J YOSHIZUMI, M EURE, J ARMSTRONG, P KILBURN, D MARK, B PETRUS, R WELLS, P GREENSPAN, J THAYER, D STERN, WH IRVINE, AR STONE, RD BALLESTEROS, F MORRIS, B NARAHARA, M WANNER, M LEAN, JS LIGGETT, PE RYAN, SJ WALONKER, AF HOWARD, E CLARK, T DELGADO, S NICHOLS, T ROZIER, MR TETREAULT, G FEDERMAN, JL FISCHER, D SARIN, LK TASMAN, WS REBER, R NICHOL, J HUTTON, WL FULLER, DG JOST, B SNYDER, WR SPENCER, WB VAISER, A ANDERSON, T POWELL, D DALRYMPLE, D NORK, C AGUADO, H EVANS, R BARR, CC ISERNHAGEN, RA JAEGERS, K RADTKE, ND WOOD, WJ WAGNER, F WHITTINGTON, GK CARPENTER, M COONS, K GILKEY, LA ROGERS, C SAUER, L HUELSMAN, S SLADE, E RAMSAY, RC CANTRILL, HL KNOBLOCK, WH RYAN, EH COOK, S MCDONOUGH, G MONAHAN, M PHILIP, D PONWITH, L STINSON, L ANDERSON, K OESTREICH, N MCMICHAEL, B VAGSTAD, G IRVINE, A HILTON, G LONN, L SCHWARTZ, A HOFFMAN, J HILLIS, A AFIFI, AA FINKELSTEIN, D MCLEAN, EB RUDISILL, AS WILKINSON, CP ABRAMS, GW DAVIS, MD MOWERY, R DUDLEY, P GOLDBERG, I MCLAUGHLIN, J RATHJEN, A HUBBARD, L AF AZEN, SP BARLOW, W BOONE, DC QUILLENTHOMAS, B CHEN, A LEE, MB LINTON, KLP LAI, MY LEE, K BOCHYNSKI, E LUNSFORD, M COX, MS BLUMENKRANZ, MS MARGHERIO, RR MURPHY, PL TRESE, MT WILLIAMS, GA WITKOP, C MANATREY, P LICHTERMAN, S CUMMING, K MCCURLEY, S SNYDER, V COX, S BRIDGES, G JOHNSON, J SOBEL, J STREASICK, P VALENZUELA, CL FLYNN, H BLANKENSHIP, GW CLARKSON, J OLSEN, K VANDENBROUCKE, R ROBEY, M ESPINAL, M ATTAWAY, J BUZNEGO, A CARRICO, D DENBESTE, B EUGENIDES, J LEMKIN, P KIPPENBROCK, R MCCLINTOCH, M NODA, N OLIVA, O PHILLIPS, B HESS, D DURIA, E MCCUEN, BW ANDERSON, B DEJUAN, E JAFFE, GJ MACHEMER, R STEFANSSON, E TIEDEMAN, JS ANDERSON, MM SCHIRMER, R BENETZ, BA AABERG, TM MEREDITH, TA KAPLAN, HJ STERNBERG, P CURTIS, L BOYLES, D MOORE, K LASALLE, J GILMAN, J MAIO, M SWORDS, R FREEMAN, HM TOLENTINO, FI DORRIEN, K BUSBY, A RAPP, E ANDERSON, S FRIEDMAN, G IMMERMAN, R MORANDI, T ODAY, T ROSENBLUM, A GLASER, BM DEBUSTROS, S MICHELS, R ALFORD, A HUPP, J NUNEZ, MA GEORGE, T BURTON, T HAN, DA MIELER, WF REKOW, S PRESCOTT, A RICHIE, MN WIPPLINGER, W KREIGER, A DIDDIE, KR SIDIKARO, J YOSHIZUMI, M EURE, J ARMSTRONG, P KILBURN, D MARK, B PETRUS, R WELLS, P GREENSPAN, J THAYER, D STERN, WH IRVINE, AR STONE, RD BALLESTEROS, F MORRIS, B NARAHARA, M WANNER, M LEAN, JS LIGGETT, PE RYAN, SJ WALONKER, AF HOWARD, E CLARK, T DELGADO, S NICHOLS, T ROZIER, MR TETREAULT, G FEDERMAN, JL FISCHER, D SARIN, LK TASMAN, WS REBER, R NICHOL, J HUTTON, WL FULLER, DG JOST, B SNYDER, WR SPENCER, WB VAISER, A ANDERSON, T POWELL, D DALRYMPLE, D NORK, C AGUADO, H EVANS, R BARR, CC ISERNHAGEN, RA JAEGERS, K RADTKE, ND WOOD, WJ WAGNER, F WHITTINGTON, GK CARPENTER, M COONS, K GILKEY, LA ROGERS, C SAUER, L HUELSMAN, S SLADE, E RAMSAY, RC CANTRILL, HL KNOBLOCK, WH RYAN, EH COOK, S MCDONOUGH, G MONAHAN, M PHILIP, D PONWITH, L STINSON, L ANDERSON, K OESTREICH, N MCMICHAEL, B VAGSTAD, G IRVINE, A HILTON, G LONN, L SCHWARTZ, A HOFFMAN, J HILLIS, A AFIFI, AA FINKELSTEIN, D MCLEAN, EB RUDISILL, AS WILKINSON, CP ABRAMS, GW DAVIS, MD MOWERY, R DUDLEY, P GOLDBERG, I MCLAUGHLIN, J RATHJEN, A HUBBARD, L TI VITRECTOMY WITH SILICONE OIL OR PERFLUOROPROPANE GAS IN EYES WITH SEVERE PROLIFERATIVE VITREORETINOPATHY - RESULTS OF A RANDOMIZED CLINICAL-TRIAL - SILICONE STUDY REPORT .2. SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PERFLUOROCARBON GASES; MANAGEMENT; COMPLICATIONS AB Between September 1987 and October 1990, 265 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy were treated with vitrectomy and randomized to treatment with perfluoropropane gas or silicone oil; 131 eyes had undergone no prior vitrectomy (group 1) while 134 eyes had undergone vitrectomy with intraocular gas tamponade (group 2). At the last examination, there were no differences between perfluoropropane gas and silicone oil in achieving visual acuity greater than or equal to 5/200 (43% vs 45% for group 1, 38% vs 33% for group 2) and complete posterior retinal reattachment (73% vs 64% for group 1, 73% vs 61% for group 2). For group 1 eyes followed up for at least 18 months, there was an advantage favoring perfluoropropane gas in achieving complete posterior retinal reattachment (83% vs 60% at 36 months, P=.045). The rates of reoperation and keratopathy were similar, while hypotony was more prevalent in eyes randomized to perfluoropropane gas (group 2). Regardless of tamponade, groups 1 and 2 had similar anatomic and visual success. However, hypotony was twice as prevalent in group 2 (perfluoropropane), and the prevalence of keratopathy increased with follow-up in group 2 (either tamponade). Either tamponade produced better results than those seen with sulfur hexafluoride gas (Silicone Study Report 1). C1 UNIV SO CALIF, CTR COORDINATING, LOS ANGELES, CA 90089 USA. ASSOCIATED RETINAL CONSULTANTS, ROYAL OAK, MI USA. UNIV MIAMI, SCH MED, BASCOM PALMER EYE INST, MIAMI, FL 33152 USA. DUKE UNIV, MED CTR, DURHAM, NC 27710 USA. EMORY UNIV, SCH MED, ATLANTA, GA 30322 USA. RETINA ASSOCIATES, BOSTON, MA USA. JOHNS HOPKINS UNIV HOSP, WILMER OPHTHALMOL INST, BALTIMORE, MD 21205 USA. MED COLL WISCONSIN, INST EYE, MILWAUKEE, WI 53226 USA. UNIV CALIF LOS ANGELES, JULES STEIN EYE INST, LOS ANGELES, CA 90024 USA. UNIV CALIF SAN FRANCISCO, SCH MED, SAN FRANCISCO, CA 94143 USA. UNIV SO CALIF, DOHENY EYE INST, LOS ANGELES, CA 90089 USA. WILLS EYE HOSP & RES INST, PHILADELPHIA, PA 19107 USA. TEXAS RETINA ASSOCIATES, DALLAS, TX USA. KENTUCKY RETINA GRP, LOUISVILLE, KY USA. KENTUCKY RETINA GRP, LEXINGTON, KY USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV CALIF SAN FRANCISCO, CTR FUNDUS PHOTOG READING, SAN FRANCISCO, CA 94143 USA. NEI, BETHESDA, MD 20892 USA. UNIV WISCONSIN, CTR FUNDUS PHOTOG READING, MADISON, WI 53706 USA. DOW CORNING CORP, SERV MED RES, MIDLAND, MI 48640 USA. RP AZEN, SP (reprint author), UNIV SO CALIF, SCH MED,DEPT PREVENT MED,DIV BIOMETRY, 1420 SAN PABLO AVE, PMB B101, LOS ANGELES, CA 90033 USA. NR 18 TC 117 Z9 120 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1992 VL 110 IS 6 BP 780 EP 792 PG 13 WC Ophthalmology SC Ophthalmology GA HX947 UT WOS:A1992HX94700017 ER PT J AU REBLIN, T RADER, DJ BEISIEGEL, U GRETEN, H BREWER, HB AF REBLIN, T RADER, DJ BEISIEGEL, U GRETEN, H BREWER, HB TI CORRELATION OF APOLIPOPROTEIN(A) ISOPROTEINS WITH LP(A) DENSITY AND DISTRIBUTION IN FASTING PLASMA SO ATHEROSCLEROSIS LA English DT Article DE ATHEROSCLEROSIS; LIPOPROTEINS; CHOLESTEROL; TRIGLYCERIDES ID LINKED IMMUNOSORBENT-ASSAY; GLYCOPROTEIN PHENOTYPES; LIPOPROTEIN CHOLESTEROL; MONOCLONAL-ANTIBODIES; GEL-ELECTROPHORESIS; SIZE HETEROGENEITY; DISEASE; QUANTIFICATION; PRECIPITATION; ASSOCIATION AB Lp(a) is an LDL-like lipoprotein which contains an additional apolipoprotein called apo(a). Apo(a) exhibits a significant size polymorphism and its size is inversely correlated with plasma Lp(a) levels. We investigated the distribution of different apo(a) isoproteins in lipoprotein density fractions. Fasting plasma samples were subjected to non-equilibrium density gradient ultracentrifugation. After SDS-PAGE and anti-apo(a) immunoblotting, apo(a) concentrations in individual density fractions were evaluated by densitometry. In series I, analysis of selected density fractions from 35 coronary heart disease (CHD) patients demonstrated that although most of the apo(a) was present in the Lp(a) density range, apo(a) was consistently found in both the VLDL and IDL fractions as well. In series II, density fractions from 9 normolipidemic subjects with 6 different apo(a) isoproteins were evaluated. A strong association between the size of the apo(a) isoprotein and the density of the associated Lp(a) particle was established (r = 0.976, P < 0.001). Lp(a) densities ranged from 1.057 g/ml for the B isoprotein to 1.09 g/ml for the S5 isoprotein. Overall, 75% of the total apo(a) was detected in the Lp(a) density range (d = 1.05-1.12 g/ml), with 9% and 10% in the LDL (d = 1.019-1.05 g/ml) and HDL (d = 1.12-1.21 g/ml) fractions, respectively. VLDL contained an average of 4% of the total apo(a) in fasting normolipidemic plasma. Two hypertriglyceridemic subjects had substantially greater amounts of apo(a) in the fasting triglyceride-rich fraction. The results of this study indicate that the size of the apo(a) isoprotein strongly influences the density of its associated Lp(a) particle and that apo(a) is consistently found in the triglyceride-rich lipoproteins of fasting plasma. C1 NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV HAMBURG,KRANKENHAUS EPPENDORF,MED KERNKLIN & POLIKLIN,W-2000 HAMBURG 20,GERMANY. NR 41 TC 31 Z9 32 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUN PY 1992 VL 94 IS 2-3 BP 223 EP 232 DI 10.1016/0021-9150(92)90247-E PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JA204 UT WOS:A1992JA20400014 PM 1385958 ER PT J AU GAUVIN, DV SANNERUD, CA HOLLOWAY, FA AF GAUVIN, DV SANNERUD, CA HOLLOWAY, FA TI 2ND-ORDER (ENVIRONMENTAL) CONDITIONING OF A TASTE-AVERSION IN RATS SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE CLASSICAL CONDITIONING; CONDITIONED TASTE AVERSION; MORPHINE; NALOXONE-PRECIPITATED WITHDRAWAL; RATS ID MORPHINE-TOLERANCE; LEARNED RESPONSE; BEHAVIOR; OVERDOSE; DEATH AB Four groups of rats (n = 10/group) were conditioned in a taste aversion task using a second-order reinforcer associated with precipitated morphine withdrawal. Rats in CS+, CS-and CS(random) groups were exposed to a chronic morphine (morphine sulfate, MS) dosing regimen. A control group received equivalent volumes of saline. All rats then received daily i.p. injections of naloxone HCl (1.0-3.2 mg/kg), inducing precipitated morphine withdrawal in group-dependent unique environments. The 4-h withdrawal trials were terminated by a 20 mg/kg MS injection (MS treatment groups only) and returned to their home cage. After a 1-week wash-out was imposed, all subjects were exposed to a conditioned taste aversion (CTA) task using environmental stimuli (CS1) from Phase 1 paired with saccharin (CS2) in a second-order conditioning procedure. The CS+ group developed a significant CTA; the CS- and CS(random) groups increased their consumption of saccharin. The saline group was unaffected by the treatment conditions. The data demonstrate the salience and importance of environmental stimuli and suggest a role for such conditioning in drug relapse phenomena. C1 NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET LAB,BALTIMORE,MD 21224. RP GAUVIN, DV (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,DEPT PSYCHIAT & BEHAV SCI,PSYCHOBIOL RES LABS,OKLAHOMA CITY,OK 73190, USA. NR 33 TC 5 Z9 5 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUN PY 1992 VL 3 IS 3 BP 249 EP 254 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JC919 UT WOS:A1992JC91900008 ER PT J AU SANGER, DJ TERRY, P KATZ, JL AF SANGER, DJ TERRY, P KATZ, JL TI MEMANTINE HAS PHENCYCLIDINE-LIKE BUT NOT COCAINE-LIKE DISCRIMINATIVE STIMULUS EFFECTS IN RATS SO BEHAVIOURAL PHARMACOLOGY LA English DT Note DE AMANTADINE; COCAINE; DRUG DISCRIMINATION; MEMANTINE; PHENCYCLIDINE; RAT ID RECEPTORS AB It has recently been reported that the amantadine derivative, memantine, which is used in the treatment of Parkinsonism, has N-methyl-D-aspartate (NMDA) antagonist properties. In order to investigate whether the behavioural effects of memantine could also be mediated through this mechanism the drug was administered to rats trained to discriminate phencyclidine (3 mg/kg) from saline. Memantine produced a dose-related (2.5-10 mg/kg) substitution for phencyclidine. Neither amantadine nor cocaine substituted for phencyclidine. In rats trained to discriminate cocaine (10 mg/kg) memantine did not substitute. These results show that memantine has phencyclidine-like but not cocaine-like discriminative stimulus effects indicating that the behavioural actions of memantine, like those of phencyclidine, are probably produced by a non-competitive inhibition of NMDA receptors. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP SANGER, DJ (reprint author), SYNTHELABO LERS,RECH,31 AVE PV COUTURIER,F-92220 BAGNEUX,FRANCE. OI Katz, Jonathan/0000-0002-1068-1159 NR 23 TC 29 Z9 29 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUN PY 1992 VL 3 IS 3 BP 265 EP 268 PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JC919 UT WOS:A1992JC91900011 ER PT J AU BUCHNER, J BRINKMANN, U PASTAN, I AF BUCHNER, J BRINKMANN, U PASTAN, I TI RENATURATION OF A SINGLE-CHAIN IMMUNOTOXIN FACILITATED BY CHAPERONES AND PROTEIN DISULFIDE ISOMERASE SO BIO-TECHNOLOGY LA English DT Article ID RNA-POLYMERASE; ATP; B3 AB B3(Fv)-PE38KDEL, a recombinant immunotoxin, forms inclusion bodies when produced in Escherichia coli. In renaturation experiments, nonspecific aggregation of non-native polypeptide chains, and the formation of incorrect disulfide linkages lead to inactive molecules. To prevent these side reactions, we added molecular chaperones and protein disulfide isomerase (PDI) to the refolding buffer. Both DnaK and GroEL/S influenced the reactivation process. GroEL alone inhibited reactivation, but in the presence of ATP, GroEL and GroES significantly increased the yield of active protein. DnaK also increased the yield of properly folded protein and the stimulating effect of DnaK was also observed using immobilized Dnak, which can be used repeatedly without significant loss of activity. PDI, which catalyzes disulfide bridging of proteins, so stimulated reactivation of the immunotoxin. Under optimum conditions, reactivation yields in the presence of PDI were about twice that obtained with nonenzymatic disulfide bond formation. Furthermore, DnaK and PDI were additive when renaturation was performed in the presence of both proteins. C1 NCI, DIV CANC BIOL,MOLEC BIOL LAB,9000 ROCKVILLE PIKE, 37-4E16, BETHESDA, MD 20892 USA. RI Buchner, Johannes/A-2651-2010 NR 23 TC 72 Z9 73 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD JUN PY 1992 VL 10 IS 6 BP 682 EP 685 DI 10.1038/nbt0692-682 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA JH553 UT WOS:A1992JH55300027 PM 1369490 ER PT J AU MCCONNELL, FM SHEARS, SB LANE, PJL SCHEIBEL, MS CLARK, EA AF MCCONNELL, FM SHEARS, SB LANE, PJL SCHEIBEL, MS CLARK, EA TI RELATIONSHIPS BETWEEN THE DEGREE OF CROSS-LINKING OF SURFACE-IMMUNOGLOBULIN AND THE ASSOCIATED INOSITOL 1,4,5-TRISPHOSPHATE AND CA2+ SIGNALS IN HUMAN B-CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN TYROSINE PHOSPHORYLATION; INTRACELLULAR IONIZED CALCIUM; ANTIGEN RECEPTOR COMPLEX; LYMPHOCYTES-B; PHOSPHOLIPASE-C; MOLECULAR-COMPONENTS; ACTIVATION; STIMULATION; IGM; TRISPHOSPHATE AB Cross-linking of surface immunoglobulin (Ig) receptors on human B cells leads to the activation of a tyrosine kinase. The activated tyrosine kinase subsequently phosphorylates a number of substrates, including phospholipase C-gamma. This enzyme breaks down phosphoinositol bisphosphate to form two intracellular messengers, diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C and the release of intracellular Ca2+ respectively. We have used h.p.l.c. and flow cytometry to measure accurately the inositol phosphate turnover and Ca2+ release in anti-Ig-stimulated human B cells. In particular, we have examined the effect of dose of the cross-linking antibody on the two responses. The identity of putative messenger inositol phosphates has been verified by structural analysis, and the amounts of both inositol phosphates and Ca2+ present have been quantified. In the Ramos Burkitt lymphoma. which is verv sensitive to stimulus through its Ig receptors. both inositol phosphate production and Ca2+ release were found to be related to the dose of anti-Ig antibody applied. This suggests that phospholipase C-mediated signal transduction in human B cells converts the degree of cross-linking of the immunoglobulin receptor quantitatively into intracellular signals. C1 UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. NIEHS,LCMP,RES TRIANGLE PK,NC 27709. RI Clark, Edward/K-3462-2012 FU NCRR NIH HHS [RR00166]; NIDCR NIH HHS [DE-08229]; NIGMS NIH HHS [GM-42508] NR 55 TC 19 Z9 19 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 1992 VL 284 BP 447 EP 455 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY203 UT WOS:A1992HY20300024 PM 1599430 ER PT J AU EGAN, MF HYDE, TM TIRSCHWELL, DL KLEINMAN, JE WEINBERGER, DR AF EGAN, MF HYDE, TM TIRSCHWELL, DL KLEINMAN, JE WEINBERGER, DR TI LATERALITY OF APPENDICULAR TARDIVE-DYSKINESIA IN CHRONIC-SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Article ID LEFT HEMISPHERE DYSFUNCTION; ASYMMETRY; BRAIN; DOPAMINE; PATHOLOGY AB The notion that the neuropathology of schizophrenia is lateralized is supported, in part, by findings of asymmetries in tardive dyskinesia (TD). To verify the existence of asymmetric TD, this study used the AIMS examination to look for lateralization of limb movements in a sample of 58 patients with TD. Patients with schizophrenia were compared with patients with affective and schizoaffective disorders. Asymmetry was seen in the majority of patients, regardless of psychiatric diagnosis. There was no preference for one side over the other. In a subgroup of 16 patients rated repeatedly over 13 weeks, the presence and sidedness of asymmetry fluctuated. At least four ratings were needed to accurately predict the presence and sidedness of "persistent" asymmetry. This study does not support the notion that there is a consistent, lateralized asymmetry of TD in patients with schizophrenia. Moreover, it raises questions about the reliability of assessment of persistent laterality in TD using a single exam. C1 CORNELL UNIV,MED CTR,COLL MED,NEW YORK,NY 10021. RP EGAN, MF (reprint author), NIMH,NEUROSCI RES CTR,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 44 TC 1 Z9 1 U1 2 U2 2 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 JUN 1 PY 1992 VL 31 IS 11 BP 1098 EP 1109 DI 10.1016/0006-3223(92)90154-R PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JK718 UT WOS:A1992JK71800003 PM 1525274 ER PT J AU WELCH, JE SWINNEN, JV OBRIEN, DA EDDY, EM CONTI, M AF WELCH, JE SWINNEN, JV OBRIEN, DA EDDY, EM CONTI, M TI UNIQUE ADENOSINE 3',5'-CYCLIC-MONOPHOSPHATE PHOSPHODIESTERASE MESSENGER RIBONUCLEIC-ACIDS IN RAT SPERMATOGENIC CELLS - EVIDENCE FOR DIFFERENTIAL GENE-EXPRESSION DURING SPERMATOGENESIS SO BIOLOGY OF REPRODUCTION LA English DT Article ID MOUSE OOCYTE MATURATION; NUCLEOTIDE PHOSPHODIESTERASE; MORPHOLOGICAL CHARACTERIZATION; CAMP PHOSPHODIESTERASE; AMP PHOSPHODIESTERASE; DNA FRAGMENTS; SERTOLI-CELL; IN-VITRO; INHIBITORS; RNA AB Four cAMP phosphodiesterase (cAMP-PDE) genes (ratPDE1, ratPDE2, ratPDE3, and ratPDE4) are expressed in the rat testis (Swinnen et al., PNAS USA 1989; 86:5325). Since multiple ratPDE1 and ratPDE2 mRNAs were present in male germ cells, their developmental expression was investigated by using purified spermatogenic cell populations. RatPDE1 mRNAs (4.0 and 2.8 kb) were found to be abundant in pachytene spermatocytes. RatPDE1 mRNA levels were decreased in round spermatids and absent from condensing spermatids/residual bodies. However, multiple ratPDE2 mRNAs (4.0, 3.5, 3.1, 2.8, and 2.4 kb) were abundant in round spermatids, and lower amounts were present in condensing spermatids/residual bodies. Transcripts related to ratPDE2 were also present in mouse round spermatids. Chromatography of germ cell cytosol identified two peaks of cAMP-PDE activity. Whereas peak A was evident in all germ cell populations examined, peak B was present in pachytene spermatocytes and round spermatids, but was at the limit of detection in condensing spermatids/residual bodies. The large decrease in peak B activity in condensing spermatids/residual bodies may be related to the drop in ratPDE1 mRNA levels observed during spermatogenesis. The sustained peak A activity in condensing spermatids/residual bodies coincides with the presence of ratPDE2 mRNA in these cells and suggests that the ratPDE2 enzyme may function during spermiogenesis and in spermatozoa. C1 UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & DNA,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PHYSIOL,CHAPEL HILL,NC 27599. RP WELCH, JE (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,BLDG 101,C4-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Swinnen, Johannes/0000-0002-7720-5077 FU NICHD NIH HHS [P30-HD-18968, HD-20788, HD-26485, R01 HD026485] NR 56 TC 24 Z9 24 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 1992 VL 46 IS 6 BP 1027 EP 1033 DI 10.1095/biolreprod46.6.1027 PG 7 WC Reproductive Biology SC Reproductive Biology GA HV727 UT WOS:A1992HV72700007 PM 1327199 ER PT J AU NAM, JM AF NAM, JM TI SAMPLE-SIZE DETERMINATION FOR CASE CONTROL STUDIES AND THE COMPARISON OF STRATIFIED AND UNSTRATIFIED ANALYSIS SO BIOMETRICS LA English DT Article DE CASE-CONTROL STUDIES; COCHRAN TEST; OPTIMUM ALLOCATION; SAMPLE SIZE ID SIMPLE APPROXIMATION; PROPORTIONS; POWER AB Woolson, Bean, and Rojas (1986, Biometrics 42, 927-932) present a simple approximation of sample size for Cochran's (1954, Biometrics 10, 417-451) test for detecting association between exposure and disease. It is useful in the design of case-control studies. We derive a sample size formula for Cochran's statistic with continuity correction which guarantees that the actual Type I error rate of the test does not exceed the nominal level. The corrected sample size is necessarily larger than the uncorrected one given by Woolson et al. and the relative difference between the two sample sizes is considerable. Allocation of equal number of cases and controls within each stratum is asymptotically optimal when the costs per case and control are the same. When any effect of stratification is absent, Cochran's stratified test, although valid, is less efficient than the unstratified one except for the important case of a balanced design. RP NAM, JM (reprint author), NCI,MATH STAT & APPL MATH SECT,BIOSTAT BRANCH,EPN 403,BETHESDA,MD 20892, USA. NR 15 TC 17 Z9 17 U1 1 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1992 VL 48 IS 2 BP 389 EP 395 DI 10.2307/2532298 PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA HY938 UT WOS:A1992HY93800004 PM 1637968 ER PT J AU HU, YL ZIFFER, H LI, GY YEH, HJC AF HU, YL ZIFFER, H LI, GY YEH, HJC TI MICROBIAL OXIDATION OF THE ANTIMALARIAL DRUG ARTEETHER SO BIOORGANIC CHEMISTRY LA English DT Article ID ARTEMISININ; METABOLISM C1 NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. RP HU, YL (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 15 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 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD JUN PY 1992 VL 20 IS 2 BP 148 EP 154 DI 10.1016/0045-2068(92)90035-2 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA HZ571 UT WOS:A1992HZ57100006 ER PT J AU AYROLDI, E BLASI, E VARESIO, L WILTROUT, RH AF AYROLDI, E BLASI, E VARESIO, L WILTROUT, RH TI INHIBITION OF PROLIFERATION OF RETROVIRUS-IMMORTALIZED MACROPHAGES BY LPS AND IFN-GAMMA - POSSIBLE AUTOCRINE DOWN-REGULATION OF CELL-GROWTH BY INDUCTION OF IL1 AND TNF SO BIOTHERAPY LA English DT Article DE AUTOCRINE; CYTOKINES; IMMORTALIZED; MACROPHAGES; PROLIFERATION ID TUMOR NECROSIS FACTOR; FRESH BONE-MARROW; V-MYC ONCOGENES; INTERFERON-GAMMA; BACTERIAL LIPOPOLYSACCHARIDES; C3H-HEJ MICE; LIPID-A; RECOMBINANT INTERLEUKIN-1; MOUSE MACROPHAGES; ACTIVATING FACTOR AB The GG2EE macrophage tumor cell line was previously established by immortalization of C3H/HeJ mouse bone marrow cells with the J2 retrovirus which contains the v-myc and v-raf oncogenes. Studies on the control of GG2EE cell proliferation in vitro have recently been performed. We observed that the combination of 5-25 U/ml recombinant mouse interferon-gamma (rmIFN-gamma) plus 0.03-0.3-mu-g/ml lipopolysaccharide (LPS) markedly inhibited the proliferation of GG2EE cells (by >95%) in vitro, while either agent alone inhibited only by <40% and 0-10%, respectively. Subsequent studies established that biologically active IL1-like (2-4 U/ml) and TNF alpha-like (50-100 U/ml) activities were released into the supernatants of LPS-treated GG2EE cells. The combination of IFN-gamma + LPS induced more (6-8 U/ml) IL1 release. These results suggested that the inhibition of proliferation of GG2EE cells by IFN-gamma + LPS could have been mediated in part by cytokines produced by the cells themselves. rhIL1-alpha at a concentration of 10 U/ml inhibited GG2EE proliferation by 25-30%, while rmIFN-gamma (25 U/ml) + rhIL1-alpha (10 U/ml) inhibited proliferation by 98%. Thus, 10 U/ml rhIL1-alpha could completely replace LPS in the LPS + rmIFN-gamma combination. Further, the combination of low doses of rhIL1-alpha (0.1 to 1 U/ml) plus rmTNF-alpha (250 U/ml), which together inhibited proliferation by <20% synergized with doses of 5 to 25 U/ml rmIFN-gamma to inhibit proliferation of GG2EE cells by 98-99%. These results suggest that cytokines produced by the cells themselves can synergize with rmIFN-gamma to inhibit the oncogene-driven proliferation of GG2EE cells. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. RI varesio, luigi/J-8261-2016; Blasi, Elisabetta/F-5870-2015; OI varesio, luigi/0000-0001-5659-2218; Blasi, Elisabetta/0000-0002-4202-8293; Ayroldi, Emira/0000-0002-9073-7297 NR 49 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PD JUN PY 1992 VL 4 IS 4 BP 267 EP 276 DI 10.1007/BF02172656 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA JC409 UT WOS:A1992JC40900004 PM 1622740 ER PT J AU DEGUCHI, Y KIRSCHENBAUM, A KEHRL, JH AF DEGUCHI, Y KIRSCHENBAUM, A KEHRL, JH TI A DIVERGED HOMEOBOX GENE IS INVOLVED IN THE PROLIFERATION AND LINEAGE COMMITMENT OF HUMAN HEMATOPOIETIC PROGENITORS AND HIGHLY EXPRESSED IN ACUTE MYELOGENOUS LEUKEMIA SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR; MYELOID-LEUKEMIA; MESSENGER-RNA; BONE-MARROW; STEM-CELLS; PROTEIN; GROWTH; IDENTIFICATION; DOMAIN C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 49 TC 43 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1992 VL 79 IS 11 BP 2841 EP 2848 PG 8 WC Hematology SC Hematology GA JA203 UT WOS:A1992JA20300005 PM 1375114 ER PT J AU HIRUMA, K HIRSCH, R PATCHEN, M BLUESTONE, JA GRESS, RE AF HIRUMA, K HIRSCH, R PATCHEN, M BLUESTONE, JA GRESS, RE TI EFFECTS OF ANTI-CD3 MONOCLONAL-ANTIBODY ON ENGRAFTMENT OF T-CELL DEPLETED BONE-MARROW ALLOGRAFTS IN MICE - HOST T-CELL SUPPRESSION, GROWTH-FACTORS, AND SPACE SO BLOOD LA English DT Article ID GRAFT-REJECTION; TRANSPLANT RECIPIENTS; LYMPHOCYTES-T; APLASTIC-ANEMIA; OKT3; ANTIGEN; INVIVO; EXPERIENCE; ACTIVATION; LEUKEMIA C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814. NR 40 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1992 VL 79 IS 11 BP 3050 EP 3058 PG 9 WC Hematology SC Hematology GA JA203 UT WOS:A1992JA20300033 PM 1534027 ER PT J AU PARASURAMAN, R GREENWOOD, PM HAXBY, JV GRADY, CL AF PARASURAMAN, R GREENWOOD, PM HAXBY, JV GRADY, CL TI VISUOSPATIAL ATTENTION IN DEMENTIA OF THE ALZHEIMER TYPE SO BRAIN LA English DT Article ID CEREBRAL METABOLIC ASYMMETRIES; NUCLEUS RAPHE DORSALIS; MILD SENILE DEMENTIA; VISUAL-ATTENTION; SPATIAL ATTENTION; CLINICAL-DIAGNOSIS; DIVIDED ATTENTION; SELECTIVE ATTENTION; COGNITIVE DEFICITS; DIRECTED ATTENTION AB Cue-directed shifts of spatial attention were examined for a letter-discrimination task in 15 patients with mild to moderate dementia of the Alzheimer type (DAT) and 15 healthy, age-matched controls. Spatial cues were valid, invalid or neutral in indicating probable target location and were presented either centrally at fixation or peripherally 6.7-degrees to the left or right of fixation. Stimulus-onset asynchrony (SOA) between cue and target was varied between 200 ms and 2000 ms. Reaction time (RT) benefits conferred by valid cues did not differ between the DAT group and the controls. However, RT costs incurred by invalid cues were significantly greater in the DAT group than in the control group. Group differences in RT costs plus benefits occurred at short SOAs (< 500 ms) for peripheral cues and at long SOAs (> 500 ms) for central cues. Reaction time costs plus benefits were correlated with right-left asymmetry in resting levels of cerebral glucose metabolism in the superior parietal lobe for DAT patients but not for controls. The results indicate that focusing of attention to spatial location is intact in early DAT, whereas the disengagement of visuospatial attention is impaired. Automatic attention shifts elicited by peripheral cues reveal abnormalities earlier than attention shifts initiated 'effortfully' by central cues. Intact focusing and impaired disengagement of visuospatial attention may be linked to dysfunction in early DAT of cortico-cortical networks linking the posterior parietal and frontal lobes. C1 CATHOLIC UNIV AMER, COGNIT SCI LAB, WASHINGTON, DC 20064 USA. NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. RP PARASURAMAN, R (reprint author), CATHOLIC UNIV AMER, DEPT PSYCHOL, WASHINGTON, DC 20064 USA. FU NIA NIH HHS [AG07569] NR 102 TC 213 Z9 215 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 1992 VL 115 BP 711 EP 733 DI 10.1093/brain/115.3.711 PN 3 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JF845 UT WOS:A1992JF84500004 PM 1628198 ER PT J AU HARFORD, TC AF HARFORD, TC TI FAMILY HISTORY OF ALCOHOLISM IN THE UNITED-STATES - PREVALENCE AND DEMOGRAPHIC CHARACTERISTICS SO BRITISH JOURNAL OF ADDICTION LA English DT Article ID ADOPTEES RAISED APART AB National estimates of the prevalence of family history for alcoholism in the USA were investigated using a general population sample of 43 809 respondents 18 years of age and older. Approximately 38% of the total sample reported a positive history for alcoholism. Positive reports were highest for Native Americans and lowest for Asian Americans. RP HARFORD, TC (reprint author), NATL INST ALCOHOL ABUSE & ALCOHOLISM,DIV BIOMET & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20879, USA. NR 11 TC 28 Z9 28 U1 1 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD JUN PY 1992 VL 87 IS 6 BP 931 EP 935 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA HZ735 UT WOS:A1992HZ73500019 PM 1525535 ER PT J AU CASSEDY, JH AF CASSEDY, JH TI NUMBERING THE NORTHS MEDICAL EVENTS - HUMANITARIANISM AND SCIENCE IN CIVIL-WAR STATISTICS SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Article RP CASSEDY, JH (reprint author), NATL LIB MED,DIV HIST MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 67 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD SUM PY 1992 VL 66 IS 2 BP 210 EP 233 PG 24 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA HY196 UT WOS:A1992HY19600002 PM 1290489 ER PT J AU MCLAUGHLIN, JK BLOT, WJ FRAUMENI, JF AF MCLAUGHLIN, JK BLOT, WJ FRAUMENI, JF TI A COHORT STUDY OF STOMACH-CANCER IN A HIGH-RISK AMERICAN POPULATION - REPLY SO CANCER LA English DT Letter RP MCLAUGHLIN, JK (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1992 VL 69 IS 11 BP 2868 EP 2868 PG 1 WC Oncology SC Oncology GA HV177 UT WOS:A1992HV17700040 ER PT J AU ADAMSON, PC ZIMM, S RAGAB, AH BALIS, F STEINBERG, SM KAMEN, BA VIETTI, TJ GILLESPIE, A POPLACK, DG AF ADAMSON, PC ZIMM, S RAGAB, AH BALIS, F STEINBERG, SM KAMEN, BA VIETTI, TJ GILLESPIE, A POPLACK, DG TI A PHASE-II TRIAL OF CONTINUOUS-INFUSION 6-MERCAPTOPURINE FOR CHILDHOOD LEUKEMIA SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Note DE 6-MERCAPTOPURINE; CONTINUOUS INFUSION; LEUKEMIA ID MERCAPTOPURINE AB A phase II pediatric trial of a continuous intravenous infusion of 6-mercaptopurine (6MP) in patients with refractory leukemia was performed. The dosing schedule, 50 mg m-2 h-1 for 48 h, was based on the results of a previous phase I trial of this approach, Among the 40 children treated for acute lymphoblastic leukemia (ALL), all of whom had received prior therapy with oral 6MP, 1 complete and 1 partial response were achieved. No response was observed in 17 patients with refractory acute nonlymphocytic leukemia (ANLL). Reversible hepatotoxicity, the primary dose-limiting toxicity, was observed in approximately 50% of cases. Mucositis was encountered infrequently and was usually not severe. 6MP given on the present continuous intravenous infusion schedule overcomes the limited and variable bioavailability of oral 6MP but shows limited activity as induction agent in children with recurrent ALL. C1 EMORY UNIV,SCH MED,DIV PEDIAT HEMATOL ONCOL,ATLANTA,GA 30322. UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DALLAS,TX 75235. WASHINGTON UNIV,SCH MED,MALLINKRODT DEPT PEDIAT,ST LOUIS,MO 63110. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1992 VL 30 IS 2 BP 155 EP 157 DI 10.1007/BF00686410 PG 3 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA HV543 UT WOS:A1992HV54300014 PM 1600597 ER PT J AU SEGUIN, LR GANGES, MB TARONE, RE ROBBINS, JH AF SEGUIN, LR GANGES, MB TARONE, RE ROBBINS, JH TI SKIN-CANCER AND CHROMOSOMAL-ABERRATIONS INDUCED BY ULTRAVIOLET-RADIATION - EVIDENCE FOR LACK OF CORRELATION IN XERODERMA-PIGMENTOSUM VARIANT AND GROUP-E PATIENTS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID SISTER CHROMATID EXCHANGES; COMPLEMENTATION GROUP-C; COCKAYNE SYNDROME; CULTURED-CELLS; DNA-SYNTHESIS; LIGHT; REPAIR; SENSITIVITY; INDUCTION; STRAINS AB Ultraviolet radiation (UV) in sunlight induces an abnormally high incidence of skin cancer in patients with xeroderma pigmentosum (XP), an autosomal recessive disease with defects in the repair of damaged DNA. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblast lines from a patient with the variant form of XP, from a patient with the complementation group E form, and from two patients with the complementation group C form. In contrast to results with patients having other forms of XP, the group E and variant patients showed no abnormal increase in UV-induced chromosomal aberrations. Even in the presence of caffeine, which exacerbates the postreplication repair defect of UV-irradiated XP variant cells, there was still no abnormally elevated frequency of UV-induced chromosomal aberrations in the variant cells. These results, indicating that the level of UV-induced chromosomal aberrations is not correlated with these patients marked susceptibility to skin cancer, suggests that some mechanism other than genetic transposition is causatively related to these XP patients' high incidence of sunlight-induced skin cancer. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 29 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1992 VL 60 IS 2 BP 111 EP 116 DI 10.1016/0165-4608(92)90001-O PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JB575 UT WOS:A1992JB57500001 PM 1606553 ER PT J AU POPESCU, NC DIPAOLO, JA AF POPESCU, NC DIPAOLO, JA TI CYTOGENETICS OF CERVICAL NEOPLASIA SO CANCER GENETICS AND CYTOGENETICS LA English DT Letter ID HUMAN PAPILLOMAVIRUS-16 DNA; HELA-CELLS; INTEGRATION; CHROMOSOME-1; INDUCTION; CARCINOMA; SEQUENCES; LINES; SITES RP POPESCU, NC (reprint author), NCI,BIOL LAB,BETHESDA,MD 20892, USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1992 VL 60 IS 2 BP 214 EP 215 DI 10.1016/0165-4608(92)90024-3 PG 2 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA JB575 UT WOS:A1992JB57500024 PM 1318784 ER PT J AU EWEL, CH URBA, WJ KOPP, WC SMITH, JW STEIS, RG ROSSIO, JL LONGO, DL JONES, MJ ALVORD, WG PINSKY, CM BEVERIDGE, JM MCNITT, KL CREEKMORE, SP AF EWEL, CH URBA, WJ KOPP, WC SMITH, JW STEIS, RG ROSSIO, JL LONGO, DL JONES, MJ ALVORD, WG PINSKY, CM BEVERIDGE, JM MCNITT, KL CREEKMORE, SP TI POLYINOSINIC-POLYCYTIDYLIC ACID COMPLEXED WITH POLY-L-LYSINE AND CARBOXYMETHYLCELLULOSE IN COMBINATION WITH INTERLEUKIN-2 IN PATIENTS WITH CANCER - CLINICAL AND IMMUNOLOGICAL EFFECTS SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER CELLS; RECOMBINANT INTERLEUKIN-2; INTERFERON-ALPHA; POLY(I,C)-LC; RESPONSES; MELANOMA; TOXICITY; TRIAL; MICE AB We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater-than-or-equal-to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment. C1 NCI,FREDERICK CANC RES DEV CTR,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,POB B,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. FREDERICK MEM HOSP,FREDERICK,MD 21701. IMMUNOMED INC,WARREN,NJ 07060. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 23 TC 42 Z9 43 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 JUN 1 PY 1992 VL 52 IS 11 BP 3005 EP 3010 PG 6 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400001 PM 1591717 ER PT J AU WU, L SMYTHE, AM STINSON, SF MULLENDORE, LA MONKS, A SCUDIERO, DA PAULL, KD KOUTSOUKOS, AD RUBINSTEIN, LV BOYD, MR SHOEMAKER, RH AF WU, L SMYTHE, AM STINSON, SF MULLENDORE, LA MONKS, A SCUDIERO, DA PAULL, KD KOUTSOUKOS, AD RUBINSTEIN, LV BOYD, MR SHOEMAKER, RH TI MULTIDRUG-RESISTANT PHENOTYPE OF DISEASE-ORIENTED PANELS OF HUMAN TUMOR-CELL LINES USED FOR ANTICANCER DRUG SCREENING SO CANCER RESEARCH LA English DT Article ID HUMAN-LEUKEMIC CELLS; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; TRANSPORT PROTEINS; HUMAN-TISSUES; MDR1 GENE; CDNA; COLCHICINE; SEQUENCES; CLONING AB Disease-oriented panels of human tumor cell lines used by the National Cancer Institute for large-scale in vitro anticancer drug screening were evaluated for multidrug-resistant phenotype at the functional (in vitro drug sensitivity) and molecular levels. The cell line panels manifested a broad range of sensitivities to drugs typically associated with multidrug resistance (MDR) as well as to drugs not associated with MDR. Individual cell lines displayed unique and characteristic profiles of response. Patterns of correlated response were observed among, but not between, MDR and non-MDR drugs. Strong evidence of correlated response was limited to drugs sharing an intracellular mechanism of action. Several tumor cell lines exhibited a high degree of resistance to MDR drugs and relative sensitivity to non-MDR drugs, contained high levels of MDR-1 mRNA, and expressed cell surface P-glycoprotein detectable with one or more monoclonal antibodies. Parallel expression of all of these features representing the classic MDR phenotype was observed among members of the colon and renal tumor panels. Certain individual cell lines among other panels (lung, ovarian, melanoma, and central nervous system) also manifested some aspects of the MDR phenotype to various extents. Identification of MDR cell lines used for large-scale in vitro anticancer drug screening will facilitate interpretation of data in a way which may allow identification of new drug leads of potential value in treatment of MDR tumor cell populations. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NCI,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. NCI,BIOMETRIC RES BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NR 43 TC 144 Z9 144 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3029 EP 3034 PG 6 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400005 PM 1350507 ER PT J AU HILDESHEIM, A WEST, S DEVEYRA, E DEGUZMAN, MF JURADO, A JONES, C IMAI, J HINUMA, Y AF HILDESHEIM, A WEST, S DEVEYRA, E DEGUZMAN, MF JURADO, A JONES, C IMAI, J HINUMA, Y TI HERBAL MEDICINE USE, EPSTEIN-BARR-VIRUS, AND RISK OF NASOPHARYNGEAL CARCINOMA SO CANCER RESEARCH LA English DT Article ID TRANSFORMATION; ANTIBODIES; GUANGZHOU; CELLS; CHINA AB Herbal medicine use is thought to be linked to nasopharyngeal carcinoma (NPC) either through its ability to reactivate the Epstein-Barr virus (EBV) or through a direct promoting effect on EBV-transformed cells. To investigate this, 104 histologically confirmed NPC cases and 205 matched controls were studied in The Philippines. Blood was collected to assess antibody titers against EBV, and an interview was administered which elicited information concerning herbal medicine use and other risk factors for NPC. Subjects strongly positive for anti-EBV antibodies (Epstein-Barr nuclear antigen [EBNA]) (titers greater-than-or-equal-to 1:80) were at a 21-fold excess risk of disease (95% confidence interval, 8.4, 51.8). Herbal medicine use was also associated with NPC (relative risk, 2.5; 95% confidence interval, 1.4, 4.5). Associations persisted after adjustment for education, smoking, Chinese ancestry, and consumption of salted fish. Exposure to herbal medicines among subjects testing negative/weakly positive for anti-EBNA antibodies was not associated with an elevation in risk (relative risk, 0.6), strong positivity to anti-EBNA antibodies in the absence of herbal medicine use was associated with a significant 16-fold excess risk of disease, and exposure to herbal medicines among subjects testing strongly positive for anti-EBNA antibodies was associated with a significant 49-fold excess risk of NPC when cases were compared to controls. Similar results were obtained when other serological measures of EBV exposure were used. Anti-EBV antibody titers were elevated in herbal medicine users compared to nonusers among cases but not among control subjects. This suggests that, if herbal medicines interact with EBV in the development of NPC, they do not do so by reactivating EBV infection but rather through a direct proliferative effect on EBV-transformed cells. Although the interaction between EBV and herbal medicines is biologically plausible, larger, more detailed studies need to be conducted to validate this preliminary finding. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21205. UNIV PHILIPPINES,PHILIPPINE GEN HOSP,DEPT PATHOL,MANILA,PHILIPPINES. UNIV PHILIPPINES,PHILIPPINE GEN HOSP,DEPT EAR NOSE & THROAT,MANILA,PHILIPPINES. KYOTO UNIV,INST VIRUS RES,KYOTO 606,JAPAN. RP HILDESHEIM, A (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. NR 22 TC 29 Z9 32 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3048 EP 3051 PG 4 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400008 PM 1317256 ER PT J AU POMMIER, Y ORR, A KOHN, KW RIOU, JF AF POMMIER, Y ORR, A KOHN, KW RIOU, JF TI DIFFERENTIAL-EFFECTS OF AMSACRINE AND EPIPODOPHYLLOTOXINS ON TOPOISOMERASE-II CLEAVAGE IN THE HUMAN C-MYC PROTOONCOGENE SO CANCER RESEARCH LA English DT Article ID ANTITUMOR DRUGS; DNA CLEAVAGE; REGULATORY ELEMENTS; NUCLEOTIDE-SEQUENCE; BURKITT-LYMPHOMA; GENE-EXPRESSION; SITES; TRANSCRIPTION; CELLS; IDENTIFICATION AB Amsacrine and demethylepipodophyllotoxins (etoposide and teniposide) are potent topoisomerase II inhibitors which have optimum activity in different cancers. To investigate whether these differences are due to different activity on cellular oncogenes, drug-induced topoisomerase II cleavage sites were mapped and sequenced in the human c-myc protooncogene. In the presence of purified murine L1210 topoisomerase II, amsacrine induces prominent cleavage in the P2 promoter (site 2499/2502). Footprinting experiments indicate that topoisomerase II binds to the entire promoter region (approximately 20 base pairs on the sides of the P2 site). In the case of teniposide or etoposide, cleavage is more diffuse and markedly less at the P2 site. Mapping of cleavage sites in human small cell lung carcinoma cells (NCI N417) also shows that cleavage in the P2 promoter region is induced preferentially by amsacrine but not by demethylepipodophyllotoxins. Thus, selective gene damage among topoisomerase II inhibitors may contribute to differential anticancer activity. C1 RHONE POULENC RORER,CTR RECH VITRY ALFORTVILLE,F-94403 VITRY,FRANCE. RP POMMIER, Y (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BLDG 37,RM 5C27,BETHESDA,MD 20892, USA. NR 45 TC 68 Z9 68 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3125 EP 3130 PG 6 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400021 PM 1317259 ER PT J AU MORGAN, D WELTY, D GLICK, A GREENHALGH, D HENNINGS, H YUSPA, SH AF MORGAN, D WELTY, D GLICK, A GREENHALGH, D HENNINGS, H YUSPA, SH TI DEVELOPMENT OF AN INVITRO MODEL TO STUDY CARCINOGEN-INDUCED NEOPLASTIC PROGRESSION OF INITIATED MOUSE EPIDERMAL-CELLS SO CANCER RESEARCH LA English DT Article ID MURINE SARCOMA-VIRUS; SKIN PAPILLOMAS; MALIGNANT CONVERSION; TERMINAL DIFFERENTIATION; RAS GENE; HA-RAS; TUMOR PROGRESSION; BENZOYL PEROXIDE; V-RAS; KERATINOCYTES AB Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-ras(Ha) oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-ras(Ha)-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater-than-or-equal-to benzo(a)pyrene diolexpoxide I > N-methyl-N'-nitro-N-nitrosoguanidine greater-than-or-equal-to 4-nitroquinoline-N-oxide > N-acetoxyacetyl-aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-ras(Ha) genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-ras(Ha) keratinocytes expressed keratin 8, a marker of v-ras(Ha) expression in cultured keratinocytes. Cells in foci, but not v-ras(Ha) control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to study chemically induced focal neoplastic progression at the cellular level and to identify agents which may be selective for enhancing malignant conversion. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,BETHESDA,MD 20892. NR 45 TC 15 Z9 16 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3145 EP 3156 PG 12 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400024 PM 1375535 ER PT J AU BELINSKY, SA DEVEREUX, TR FOLEY, JF MARONPOT, RR ANDERSON, MW AF BELINSKY, SA DEVEREUX, TR FOLEY, JF MARONPOT, RR ANDERSON, MW TI ROLE OF THE ALVEOLAR TYPE-II CELL IN THE DEVELOPMENT AND PROGRESSION OF PULMONARY TUMORS INDUCED BY 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN THE A/J MOUSE SO CANCER RESEARCH LA English DT Article ID TOBACCO-SPECIFIC CARCINOGEN; LUNG-TUMORS; CHEMICAL CARCINOGENESIS; N-NITROSAMINES; DOSE-RESPONSE; F344 RATS; MICE; DNA; 4-(N-METHYL-N-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; METABOLISM AB The role of the type II cell in the development of pulmonary tumors induced in the adult A/J mouse (6 weeks of age) by treatment with a single dose (100 mg/kg, i.p.) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ( (NNK) was investigated. Twenty-four h following treatment with NNK, the concentration of O6-methylguanine was similar in Clara and type II cells. However, hyperplasias were detected only along the alveolar septa in lungs 14 weeks after carcinogen treatment. Examination of the ultrastructure of several hyperplasias revealed that the proliferating cells resembled type II pneumocytes. The proliferating cells were cuboidal in shape, with centrally localized ovoid nuclei characterized by minor indentations. Lamellar bodies, one of the major hallmarks of the type II cell, were present in the cytoplasm. The progression of pulmonary lesions was followed by sacrificing mice at 4-week intervals from 14 to 54 weeks after treatment with NNK. From 34 to 42 weeks after treatment, progression to neoplasia was demonstrated by a decline in the frequency of hyperplasias and an increase in the frequency of adenomas. Approximately 50% of the adenomas were observed arising within hyperplasias. Carcinomas appeared to increase in frequency 34 weeks after carcinogen treatment and comprised greater than 50% of the pulmonary lesions by 54 weeks. Approximately 30% of the carcinomas were observed arising within adenomas. The growth pattern of carcinomas began to change from solid to mixed (solid and papillary) 42 weeks after NNK. Moreover, electron micrographic analysis demonstrated that, within a hyperplasia, proliferating type II cells could change from cuboidal to columnar in shape and could also exhibit nuclear indentations, both characteristics displayed by the Clara cell. Thus, this divergence of the type II cell from its well characterized morphological features indicates that the selective growth advantage which these initiated cells possess can result in changes to the normal ultrastructure of this cell as it progresses toward malignancy. DNA was isolated from 20 hyperplasias and screened for the presence of an activated K-ras gene. This gene was activated in 17 of 20 lesions, with 85% of the mutations involving a GC to AT transition within codon 12 (GGT to GAT), a mutation consistent with base mispairing produced by the formation of the O6-methylguanine adduct. This specificity for activation of the K-ras gene was identical to that observed previously in adenocarcinomas induced by NNK. These results indicate that the genesis of pulmonary neoplasia induced in the A/J mouse by NNK involves formation of the O6-methylguanine adduct within type II cells, which leads to the activation of the K-ras gene, followed by proliferation of type II cells and subsequent progression to a malignant tumor. C1 NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 41 TC 143 Z9 143 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3164 EP 3173 PG 10 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400026 PM 1591728 ER PT J AU PAI, LH BATRA, JK FITZGERALD, DJ WILLINGHAM, MC PASTAN, I AF PAI, LH BATRA, JK FITZGERALD, DJ WILLINGHAM, MC PASTAN, I TI ANTITUMOR EFFECTS OF B3-PE AND B3-LYSPE40 IN A NUDE-MOUSE MODEL OF HUMAN BREAST-CANCER AND THE EVALUATION OF B3-PE TOXICITY IN MONKEYS SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; IMMUNOTOXINS AB B3 is a tumor-reactive monoclonal antibody (mAb) that binds to a limited number of normal tissues. Immunotoxins made with B3 coupled to either Pseudomonas exotoxin (PE) or recombinant forms of PE with a deletion of the cell-binding domain (LysPE40) have been shown to cause complete tumor regression in nude mice bearing a rapidly growing A431 (L. H. Pai et al., Proc. Natl. Acad. Sci. USA, 88. 3358-3362, 1991) human epidermoid carcinoma. In this study we show that an immunotoxin composed of mAb B3 when chemically coupled to LysPE40 (B3-LysPE40) led to complete regression of a slowly growing breast cancer, MCF-7, in nude mice when given i.v. every other day for five doses. mAb B3 coupled to native PE also produced significant regression of the MCF-7 tumor. The reactivity of mAb B3 was evaluated using an immunohistochemical method on the two responsive tumors, MCF-7 and A431, and compared with a typical human colon carcinoma specimen that has B3 antigen on its surface. The results showed that both A431 and MCF-7 xenograft tumors have similar reactivity to B3 when compared with the human colon carcinoma specimen. To evaluate the toxicity of B3-PE in primates, Cynomolgus monkeys received escalating doses of B3-PE i.v. on Days 1, 3, and 5. Based on antibody localization studies using frozen sections of normal human and monkey tissue, gastric, trachea, and bladder mucosal injury could have occurred. However, no clinical signs of injury or histological damage to these organs were seen at the doses administered. Chemical hepatitis due to PE was transient and well tolerated at doses up to 50-mu-g/kg for three doses. The lethal dose was about 100-mu-g/kg, and the cause of death was liver necrosis, as shown by necropsy. We conclude that mAb B3, when coupled to PE40 or PE, can produce strong antitumor activity in vivo. The similar level of reactivity of the B3 antibody in our tumor models with a surgical specimen of a human colon carcinoma and the toxicity study in monkeys indicate that therapeutic doses of B3-PE and B3-LysPE40 can be delivered without causing toxicity to normal organs that express B3 antigen. Although both B3-PE and B3-LysPE40 have antitumor activity in nude mice bearing a human xenograft, B3-LysPE40 is better tolerated and should be further evaluated as a therapeutic agent for cancer patients. C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 12 TC 32 Z9 35 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3189 EP 3193 PG 5 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400029 PM 1591729 ER PT J AU KOHN, EC SANDEEN, MA LIOTTA, LA AF KOHN, EC SANDEEN, MA LIOTTA, LA TI INVIVO EFFICACY OF A NOVEL INHIBITOR OF SELECTED SIGNAL TRANSDUCTION PATHWAYS INCLUDING CALCIUM, ARACHIDONATE, AND INOSITOL PHOSPHATES SO CANCER RESEARCH LA English DT Article ID MUSCARINIC RECEPTOR SUBTYPES; PHOSPHOLIPASE-C; MALIGNANT TRANSFORMATION; G-PROTEIN; CELLS; ONCOGENES; STIMULATION; EXPRESSION; GENES; RAS AB Aberrant signal transduction has been implicated in malignant transformation, growth, and progression. This has led to the proposal to use inhibitors of signal transduction pathways to treat cancer. One approach to circumventing potential toxicity and improving efficacy would be to target pathways upon which cancer cells selectively depend. Pathways associated with the malignant process involve calcium fluxes, the release of arachidonic acid, and the generation of phosphoinositides. In this report, CAI (L651582, NSC 609974), a substituted carboxyamido-imidazole and novel inhibitor of these selected signal transduction pathways, inhibits anchorage-dependent and -independent growth in a large series of human cancer cell lines. CAI pretreatment of HT-29 human colon cancer and 5R ras-transfected rat embryo fibroblast cells inhibits the formation and growth of experimental pulmonary metastases in nude mice. Oral administration of CAI in PEG400 vehicle arrests growth and metastasis of transplanted human melanoma and ovarian cancer xenografts. No significant gross or histological toxicity was observed at CAI doses yielding blood levels in the concentration range demonstrated to inhibit select signal transduction pathways in vitro. These data indicate the feasibility and demonstrate a potential selectivity and sensitivity of using specific signal transduction inhibitors for the experimental treatment of cancer. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,LAB ANIM SCI PROGRAM,FREDERICK,MD 21702. RP KOHN, EC (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74102] NR 27 TC 104 Z9 105 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1992 VL 52 IS 11 BP 3208 EP 3212 PG 5 WC Oncology SC Oncology GA HW134 UT WOS:A1992HW13400032 PM 1591730 ER PT J AU KOPPSCHNEIDER, A PORTIER, CJ AF KOPPSCHNEIDER, A PORTIER, CJ TI BIRTH AND DEATH DIFFERENTIATION RATES OF PAPILLOMAS IN MOUSE SKIN SO CARCINOGENESIS LA English DT Article ID NMRI MICE; CARCINOGENESIS; INITIATION; CONVERSION; MODELS; TUMORS AB A simple one-stage model for the formation of papillomas is used to evaluate data from a series of initiation/promotion/stop-promotion experiments performed on NMRI mice. These experiments used a single application of 100 nmol 7,12-dimethylbenz[a]anthracene followed by twice weekly applications of 5 nmol 12-0-tetradecanoylphorbol-13-acetate. It is shown that, on the basis of this model, the data considered here provide no evidence for a growth advantage of initiated cells versus normal cells. Although model estimates always have to be treated with utmost caution, they can at least be interpreted in a qualitative way. In consequence, it has to be concluded either that the mechanism upon which the model is based fails to describe properly the growth behaviour of initiated cells, or that initiated cells do not possess a growth advantage over normal cells, even in the presence of a promoter. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP KOPPSCHNEIDER, A (reprint author), DEUTSCH KREBSFORSCHUNGSZENTRUM,BIOSTAT ABT,NEUENHEIMER FELD 280,W-6900 HEIDELBERG,GERMANY. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 27 TC 34 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1992 VL 13 IS 6 BP 973 EP 978 DI 10.1093/carcin/13.6.973 PG 6 WC Oncology SC Oncology GA HZ880 UT WOS:A1992HZ88000011 PM 1600619 ER PT J AU KULKARNI, N ZANG, E KELLOFF, G REDDY, BS AF KULKARNI, N ZANG, E KELLOFF, G REDDY, BS TI EFFECT OF THE CHEMOPREVENTIVE AGENTS PIROXICAM AND D,L-ALPHA-DIFLUOROMETHYLORNITHINE ON INTERMEDIATE BIOMARKERS OF COLON CARCINOGENESIS SO CARCINOGENESIS LA English DT Article ID CELL-PROLIFERATION; 16,16-DIMETHYL PROSTAGLANDIN-E2; INTESTINAL CARCINOGENESIS; END-POINTS; CANCER; RATS; INDOMETHACIN; EPITHELIUM; INHIBITION; CARCINOMA AB Our previous studies have shown that dietary piroxicam, a non-steroidal anti-inflammatory drug (NSAID), and D,L-alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, act as potential chemopreventive agents in inhibiting azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The present study was designed to determine the effect of these chemopreventive agents on intermediate biomarkers, namely colonic epithelial cell proliferation and levels of prostaglandins, which can be used as effective predictors of colon cancer. Starting at 6 weeks of age, groups of animals were fed the control diet and experimental diets containing piroxicam or DFMO. At 7 weeks of age, all animals, except the vehicle controls, were injected s.c. with AOM at a dose level of 15 mg/kg body wt/week for 4 weeks. Vehicle controls received an equal volume of normal saline. Groups of animals were then killed at the end of last AOM or saline injection (baseline) and at week 4, 16, 24 and 32 following the last AOM or saline treatment. Animals intended for cell proliferation study were injected with bromodeoxyuridine (BrdU) at a dose level of 20 mg/kg body wt 1 h prior to being killed. The rate of colonic cell proliferation at all time points was assessed immunohistochemically using anti-BrdU. The levels of colonic mucosal prostaglandins were estimated by radioimmunoassay. The results indicate that carcinogen treatment increased the colonic cell proliferation measured as the crypt labeling index in proximal and distal colons and the concentrations of colonic prostaglandin E2 (PGE2) and 6-keto PGF1-alpha. The data demonstrate that DFMO significantly inhibited the AOM-induced labeling index in the distal and proximal colon at all time points, whereas piroxicam slightly decreased the labeling index. On the other hand, piroxicam exerted a pronounced inhibitory effect on the levels of both PGE2 and 6-keto PGF1-alpha. DFMO suppressed the colonic PGE2 levels to a lesser degree than piroxicam. The results demonstrate that DFMO, an inhibitor of ODC, suppresses cell proliferation, whereas piroxicam, a NSAID, inhibits prostaglandins, and emphasize the need to develop agent-dependent intermediate biomarker(s) to validate the efficacy of chemopreventive agent(s) in colon carcinogenesis. C1 AMER HLTH FDN,DIV NUTR CARCINOGENESIS,1 DANA RD,VALHALLA,NY 10595. NCI,DIV CANC CONTROL & PREVENT,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-17613, N01-CN-85095-03] NR 50 TC 38 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1992 VL 13 IS 6 BP 995 EP 1000 DI 10.1093/carcin/13.6.995 PG 6 WC Oncology SC Oncology GA HZ880 UT WOS:A1992HZ88000014 PM 1600622 ER PT J AU REDDY, BS TOKUMO, K KULKARNI, N ALIGIA, C KELLOFF, G AF REDDY, BS TOKUMO, K KULKARNI, N ALIGIA, C KELLOFF, G TI INHIBITION OF COLON CARCINOGENESIS BY PROSTAGLANDIN SYNTHESIS INHIBITORS AND RELATED-COMPOUNDS SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; AUTOCHTHONOUS INTESTINAL TUMORS; GLYCYRRHETIC ACID; PROMOTING ACTIVITY; DIETARY-FAT; PIROXICAM; RATS; MOUSE; INDOMETHACIN; CANCER AB The inhibitory effect of 40 and 80% maximum tolerated dose (MTD) levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid on colon carcinogenesis was investigated in male F344 rats. The MTD levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid as determined in male F344 rats were 500, 500, 250 and 3000 p.p.m. respectively. At 5 weeks of age, groups of male F344 rats were fed the control (AIN-76A) diet and 40 and 80% MTD levels of each test agent in AIN-76A diet. At 7 weeks of age, all animals except the vehicle (saline)-treated controls received azoxy-methane (AOM) at a dose rate of 15 mg/kg body wt, once weekly for 2 weeks. All animals were necropsied 50 weeks after the second AOM injection and colon tumor incidences were compared among the groups fed the control diet and chemopreventive agents. Animals fed 400 (80% MTD) and 200 p.p.m. (40% MTD) of piroxicam, 400 p.p.m. (80% MTD) of ibuprofen and 200 p.p.m. (80% MTD) of ketoprofen showed a significant inhibition of colon tumorigenesis as compared to those fed the control diet. Results analyzed by the linear regression method suggested a dose-dependent inhibition of colon carcinogenesis with increasing levels of piroxicam or ibuprofen. In contrast, glycyrrhetinic acid had no measurable chemopreventive effect on colon carcinogenesis. C1 NCI,DIV CANC CONTROL & PREVENT,CHEMOPREVENT BRANCH,BETHESDA,MD 20856. RP REDDY, BS (reprint author), AMER HLTH FDN,DIV NUTR CARCINOGENESIS,VALHALLA,NY 10595, USA. FU NCI NIH HHS [CP-17613, N01-CN-85095-02] NR 47 TC 139 Z9 140 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1992 VL 13 IS 6 BP 1019 EP 1023 DI 10.1093/carcin/13.6.1019 PG 5 WC Oncology SC Oncology GA HZ880 UT WOS:A1992HZ88000018 PM 1600605 ER PT J AU ABASSI, ZA GOLOMB, E KLEIN, H KEISER, HR AF ABASSI, ZA GOLOMB, E KLEIN, H KEISER, HR TI URODILATIN - A NATRIURETIC PEPTIDE OF RENAL ORIGIN SO CARDIOVASCULAR DRUG REVIEWS LA English DT Review DE URODILATION; NATRIURETIC PEPTIDE; KIDNEY ID EXPERIMENTAL HEART-FAILURE; CENTRAL NERVOUS-SYSTEM; ATRIAL PEPTIDE; SEQUENCE-ANALYSIS; ALPHA-HANP; SODIUM-EXCRETION; FACTOR PRECURSOR; BLOOD-PRESSURE; PORCINE BRAIN; RAT ATRIA AB More than three decades ago, H. W. Smith and H. E. DeWardener reported, in separate studies, that the natriuresis observed after volume expansion or sodium loading could not be attributed solely to increases in the glomerular filtration rate or changes in plasma levels of aldosterone (69,82). In addition, DeWardener showed, in a classic experiment, that infusion of blood from "volume-expanded" dogs into normal dogs induced an increase in the excretion of sodium by the recipients (82,83). These findings provided strong evidence for the existence of a circulating natriuretic substance, regulated by the central blood volume. At about the same time, Kisch reported the presence of secretory granules in guinea pig atrial cardiocytes (41). In 1976, Marie et al. demonstrated that a high salt intake, with or without desoxycorticosterone (DOCA), decreased the concentration of these granules, whereas sodium and water depletion increased their number (48). In 1979, deBold confirmed these findings, suggesting that the atrial granularity was related to changes in fluid balance in the body and that the content of these secretory granules could affect renal function (11). Two years later, deBold et al. (12) reported that injection of an extract of rat atria produced increases of approximately 30-fold and 10-fold in sodium excretion and urine flow, respectively. Injections of extracts of ventricular tissue did not exert a significant effect on these parameters (12). This work was the first to provide proof that the atria contain a natriuretic substance, which is presumably released into the circulation in response to volume expansion or other stimuli that increase atrial stretch. The substance was referred to as atrial natriuretic factor (ANF) (12), atrial natriuretic peptide (ANP), cardiodilatin (13), atriopeptin (16), or auriculin (7). Within a few years, the biochemistry, molecular biology and physiology of ANF were described. C1 NHLBI,HYPERTENS ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 84 TC 7 Z9 7 U1 0 U2 0 PU NEVA PRESS PI BRANFORD PA P O BOX 347, BRANFORD, CT 06405 SN 0897-5957 J9 CARDIOVASC DRUG REV JI Cardiovasc. Drug Rev. PD SUM PY 1992 VL 10 IS 2 BP 199 EP 210 DI 10.1111/j.1527-3466.1992.tb00246.x PG 12 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA JN615 UT WOS:A1992JN61500006 ER PT J AU CARAFOLI, E KLEE, CB AF CARAFOLI, E KLEE, CB TI NEW DEVELOPMENTS IN THE CALMODULIN FIELD - PREFACE SO CELL CALCIUM LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP CARAFOLI, E (reprint author), SWISS FED INST TECHNOL,BIOCHEM LAB,CH-8092 ZURICH,SWITZERLAND. RI Carafoli, Ernesto/K-5192-2016 OI Carafoli, Ernesto/0000-0002-7826-0094 NR 0 TC 4 Z9 4 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JUN-JUL PY 1992 VL 13 IS 6-7 BP 353 EP 354 DI 10.1016/0143-4160(92)90048-W PG 2 WC Cell Biology SC Cell Biology GA JF053 UT WOS:A1992JF05300001 ER PT J AU IKURA, M BARBATO, G KLEE, CB BAX, A AF IKURA, M BARBATO, G KLEE, CB BAX, A TI SOLUTION STRUCTURE OF CALMODULIN AND ITS COMPLEX WITH A MYOSIN LIGHT CHAIN KINASE FRAGMENT SO CELL CALCIUM LA English DT Article ID 3-DIMENSIONAL NMR-SPECTROSCOPY; RESOLUTION; PROTEINS; SPECTRA; PEPTIDE; C-13 AB The solution structure of Ca2+ ligated calmodulin and of its complex with a 26-residue peptide fragment of skeletal muscle myosin light chain kinase (skMLCK) have been investigated by multi-dimensional NMR. In the absence of peptide, the two globular domains of calmodulin adopt the same structure as observed in the crystalline form [2]. The so-called 'central helix' which is observed in the crystalline state is disrupted in solution. N-15 relaxation studies show that residues Asp78 through Ser81, located near the middle of this 'central helix', form a very flexible link between the two globular domains. In the presence of skMLCK target peptide, the peptide-protein complex adopts a globular ellipsoidal shape. The helical peptide is located in a hydrophobic channel that goes through the center of the complex and makes an angle of approximately 45-degrees with the long axis of the ellipsoid. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP IKURA, M (reprint author), NIDDKO CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Barbato, Gaetano/G-4904-2011 NR 25 TC 47 Z9 49 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JUN-JUL PY 1992 VL 13 IS 6-7 BP 391 EP 400 DI 10.1016/0143-4160(92)90052-T PG 10 WC Cell Biology SC Cell Biology GA JF053 UT WOS:A1992JF05300005 PM 1505004 ER PT J AU BINO, T FREY, JL ORTALDO, JR AF BINO, T FREY, JL ORTALDO, JR TI MECHANISM OF TARGET-CELL RECOGNITION BY CD3- LGL .1. DEVELOPMENT OF A MONOCLONAL-ANTIBODY TO A K562-ASSOCIATED TARGET-CELL ANTIGEN SO CELLULAR IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; LARGE GRANULAR LYMPHOCYTES; CYTO-TOXICITY; NK CELLS; INTERFERON; PROTEINS; LINES C1 NCI,FCRDC,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RP BINO, T (reprint author), ISRAEL INST BIOL RES,NESS ZIONA,ISRAEL. NR 33 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 1992 VL 142 IS 1 BP 28 EP 39 DI 10.1016/0008-8749(92)90266-R PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA HZ071 UT WOS:A1992HZ07100003 PM 1586958 ER PT J AU TING, CC HARGROVE, ME LIANG, SM LIANG, CM SHARROW, SO AF TING, CC HARGROVE, ME LIANG, SM LIANG, CM SHARROW, SO TI DICHOTOMY OF GLUTATHIONE REGULATION OF THE ACTIVATION OF RESTING AND PREACTIVATED LYMPHOCYTES SO CELLULAR IMMUNOLOGY LA English DT Article ID T-CELL FUNCTION; KILLER CELLS; INTRACELLULAR GLUTATHIONE; DIFFERENTIATION FACTOR; NATURAL-KILLER; FRIEND VIRUS; ANTIBODY; GENERATION; IDENTIFICATION; TRANSLOCATION C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP TING, CC (reprint author), NCI,DIV CANC BIOL DIAGN & CTR,BETHESDA,MD 20892, USA. NR 34 TC 19 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 1992 VL 142 IS 1 BP 40 EP 53 DI 10.1016/0008-8749(92)90267-S PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA HZ071 UT WOS:A1992HZ07100004 PM 1534039 ER PT J AU GOLDSTEIN, RA HURD, S AF GOLDSTEIN, RA HURD, S TI THE RISING PROBLEMS OF ASTHMA - MECHANISMS AND MANAGEMENT - INTRODUCTION SO CHEST LA English DT Editorial Material C1 NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. RP GOLDSTEIN, RA (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1992 VL 101 IS 6 SU S BP S355 EP S356 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JA186 UT WOS:A1992JA18600001 PM 1350525 ER PT J AU HURD, SS LENFANT, C AF HURD, SS LENFANT, C TI THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE ASTHMA PROGRAM SO CHEST LA English DT Article ID SELF-MANAGEMENT; EDUCATION RP HURD, SS (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1992 VL 101 IS 6 SU S BP S359 EP S361 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JA186 UT WOS:A1992JA18600003 PM 1591931 ER PT J AU PROGRAIS, LJ ZUNICH, KM AF PROGRAIS, LJ ZUNICH, KM TI NIAID PROGRAMS FOR ASTHMA RESEARCH, EDUCATION, AND OUTREACH SO CHEST LA English DT Article RP PROGRAIS, LJ (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1992 VL 101 IS 6 SU S BP S357 EP S358 DI 10.1378/chest.101.6_Supplement.357S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JA186 UT WOS:A1992JA18600002 PM 1591930 ER PT J AU WEISS, KB GERGEN, PJ CRAIN, EF AF WEISS, KB GERGEN, PJ CRAIN, EF TI INNER-CITY ASTHMA - THE EPIDEMIOLOGY OF AN EMERGING UNITED-STATES PUBLIC-HEALTH CONCERN SO CHEST LA English DT Article ID CHILDHOOD ASTHMA; PERSISTENT WHEEZE; MEXICAN-AMERICAN; SOCIAL-CLASS; VENTILATORY FUNCTIONS; CHANGING PATTERNS; PERINATAL EVENTS; NATIONAL SAMPLE; NORMAL-CHILDREN; LUNG-FUNCTION C1 GEORGE WASHINGTON UNIV,CTR HLTH POLICY RES,WASHINGTON,DC 20052. NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,BETHESDA,MD 20892. BRONX MUNICIPAL HOSP CTR,DIV GEN PEDIAT EMERGENCY MED,BRONX,NY 10461. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10461. RP WEISS, KB (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT HLTH CARE SCI,RM 2B-401,2150 PENN AVE NW,WASHINGTON,DC 20037, USA. NR 87 TC 88 Z9 89 U1 3 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1992 VL 101 IS 6 SU S BP S362 EP S367 DI 10.1378/chest.101.6_Supplement.362S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JA186 UT WOS:A1992JA18600004 PM 1591932 ER PT J AU FANANAPAZIR, L CANNON, RO TRIPODI, D PANZA, JA AF FANANAPAZIR, L CANNON, RO TRIPODI, D PANZA, JA TI IMPACT OF DUAL-CHAMBER PERMANENT PACING IN PATIENTS WITH OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY WITH SYMPTOMS REFRACTORY TO VERAPAMIL AND BETA-ADRENERGIC BLOCKER THERAPY SO CIRCULATION LA English DT Article DE DUAL-CHAMBER PACING; OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY ID MITRAL-VALVE REPLACEMENT; LEFT-VENTRICULAR HYPERTROPHY; MUSCULAR SUBAORTIC STENOSIS; SYSTOLIC ANTERIOR MOTION; SUB-AORTIC STENOSIS; OPERATIVE TREATMENT; PRESSURE-GRADIENT; SEPTAL MYOTOMY; EXERCISE PERFORMANCE; CLINICAL COURSE AB Background. Patients with obstructive hypertrophic cardiomyopathy (HCM) with symptoms refractory to drugs (beta-blockers or verapamil) are candidates for cardiac surgery (left ventricular septal myectomy or mitral valve replacement). The present study examines prospectively the ability of dual-chamber (DDD) pacing to improve symptoms and relieve left ventricular outflow obstruction in such patients. Methods and Results. Forty-four consecutive patients with obstructive HCM who had failed to benefit from pharmacotherapy underwent treadmill exercise tests, echocardiography, and cardiac catheterization before and 1.5-3 months after implantation of a DDD pacemaker. Symptoms (angina, dyspnea, palpitations, presyncope, and syncope), New York Heart Association functional class status (1.7+/-0.7 versus 3.4+/-0.5, p<0.00001), and exercise durations were improved at follow-up evaluation. This was associated with significant reduction in left ventricular outflow tract gradient (38+/-38 versus 87+/-43 mm Hg, p<0.0001) and significant increases in cardiac output and systemic arterial pressures. Notably, when pacing was discontinued and comparisons were made in sinus rhythm, treadmill exercise durations were greater and left ventricular outflow tract gradients were less at the follow-up evaluation compared with the baseline study. Conclusions. DDD pacing is an effective alternative to surgery in most patients with obstructive HCM with drug-refractory symptoms. The beneficial effects of pacing continue to be evident when pacing is acutely discontinued. C1 NHLBI,CARDIOL BRANCH,ELECTROPHYSIOL SECT,BETHESDA,MD 20892. NR 64 TC 224 Z9 225 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 JUN PY 1992 VL 85 IS 6 BP 2149 EP 2161 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HX707 UT WOS:A1992HX70700020 PM 1350522 ER PT J AU STEINBERG, D BERLINER, JA BURTON, GW CAREW, TE CHAIT, A CHISOLM, GM ESTERBAUER, H FOGELMAN, AM FOX, PL FURBERG, CD GAZIANO, JM GEY, KF GRUNDY, SM HARLAN, WR HAVEL, RJ HENNEKENS, CH HOFF, HF JACKSON, RL KAYDEN, HJ KEECH, A KRINSKY, NI MANSON, J PARTHASARATHY, S PROBSTFIELD, J PRYOR, WA RIFKIND, B STADTMAN, ER WALLACE, RB WITZTUM, JL YLAHERTTUALA, S YUSUF, S AF STEINBERG, D BERLINER, JA BURTON, GW CAREW, TE CHAIT, A CHISOLM, GM ESTERBAUER, H FOGELMAN, AM FOX, PL FURBERG, CD GAZIANO, JM GEY, KF GRUNDY, SM HARLAN, WR HAVEL, RJ HENNEKENS, CH HOFF, HF JACKSON, RL KAYDEN, HJ KEECH, A KRINSKY, NI MANSON, J PARTHASARATHY, S PROBSTFIELD, J PRYOR, WA RIFKIND, B STADTMAN, ER WALLACE, RB WITZTUM, JL YLAHERTTUALA, S YUSUF, S TI ANTIOXIDANTS IN THE PREVENTION OF HUMAN ATHEROSCLEROSIS - SUMMARY OF THE PROCEEDINGS OF A NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE WORKSHOP - SEPTEMBER 5-6, 1991, BETHESDA, MARYLAND SO CIRCULATION LA English DT Article DE ATHEROGENESIS; ATHEROSCLEROSIS; LOW DENSITY LIPOPROTEIN; FREE RADICALS; VITAMIN-E; VITAMIN-C; BETA-CAROTENE; PROBUCOL C1 UNIV CALIF LOS ANGELES,PATHOL,LOS ANGELES,CA 90024. NATL RES COUNCIL CANADA,STEACIE INST,OTTAWA K1A 0R6,ONTARIO,CANADA. UNIV CALIF SAN DIEGO,MED,LA JOLLA,CA 92093. UNIV WASHINGTON,MED,SEATTLE,WA 98195. CLEVELAND CLIN EDUC FDN,RES INST,DEPT VASC CELL BIOL,CLEVELAND,OH 44106. GRAZ UNIV,BIOCHEM,A-8010 GRAZ,AUSTRIA. UNIV CALIF LOS ANGELES,MED,LOS ANGELES,CA 90024. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,PUBL HLTH SCI,WINSTON SALEM,NC 27103. INST BIOCHEM & MOLEC BIOL,VITAMIN UNIT,BERN,SWITZERLAND. UNIV TEXAS,SW MED CTR,CTR HUMAN NUTR,DALLAS,TX 75235. NIH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,MED,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,MED & PREVENT MED,BOSTON,MA 02115. NYU MED CTR,MED,NEW YORK,NY 10016. UNIV OXFORD,CLIN TRIAL SERV UNIT,OXFORD,ENGLAND. UNIV OXFORD,DEPT CARDIOL,OXFORD,ENGLAND. TUFTS UNIV,SCH MED,BIOCHEM,BOSTON,MA 02111. HARVARD UNIV,SCH MED,MED,BOSTON,MA 02115. NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892. LOUISIANA STATE UNIV,INST BIODYNAM,BATON ROUGE,LA 70803. NHLBI,LIPID METAB ATHEROGENESIS BRANCH,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. UNIV TAMPERE,TAMPERE,FINLAND. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP STEINBERG, D (reprint author), UNIV CALIF SAN DIEGO,DIV ENDOCRINCOL & METAB 0613D,BASIC SCI BLDG,ROOM 1080,LA JOLLA,CA 92093, USA. RI Parthasarathy, Sampath/G-5602-2011 NR 0 TC 161 Z9 161 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 JUN PY 1992 VL 85 IS 6 BP 2338 EP 2344 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HX707 UT WOS:A1992HX70700051 ER PT J AU VENTURA, C MILLER, R WOLF, HP BEIER, N JONAS, R KLOCKOW, M LUES, I HANO, O SPURGEON, HA LAKATTA, EG CAPOGROSSI, MC AF VENTURA, C MILLER, R WOLF, HP BEIER, N JONAS, R KLOCKOW, M LUES, I HANO, O SPURGEON, HA LAKATTA, EG CAPOGROSSI, MC TI NOVEL DIAZINONE DERIVATIVES SEPARATE MYOFILAMENT CA2+ SENSITIZATION AND PHOSPHODIESTERASE-III INHIBITORY EFFECTS IN GUINEA-PIG MYOCARDIUM SO CIRCULATION RESEARCH LA English DT Article DE CARDIOTONIC AGENTS; DIAZINONE; CALCIUM; CA2+ SENSITIZATION; PHOSPHODIESTERASE-III ID CYCLIC-AMP PHOSPHODIESTERASE; BETA-ADRENERGIC STIMULATION; RAT CARDIAC MYOCYTES; INOTROPIC AGENTS; MYOFIBRILLAR RESPONSIVENESS; VENTRICULAR MYOCARDIUM; CONTRACTILE PROTEINS; CALCIUM; MUSCLE; RABBIT AB The inotropic state of the myocardium can be enhanced via an increase in cell Ca2+ loading or in myofilament responsiveness to Ca2+. Although different pharmacological agents combine these properties, no presently available drug acts predominantly as a myofilament sensitizer in situ. We have investigated the effects and the mechanism of action of novel diazinone derivatives, EMD 54622, EMD 53998, and EMD 54650 (developed by E. Merck, Darmstadt), on guinea pig myocardial preparations. Force- and ATPase-pCa relations in skinned fibers show differing potencies of these agents on myofilament sensitization: EMD 54622 > EMD 53998 >> EMD 54650. This is in contrast to their relative potencies to inhibit isolated myocardial phosphodiesterase III: EMD 54650 > EMD 53998 > EMD 54622. In isolated hearts studied at constant coronary flow, each of the three diazinone derivatives had a positive inotropic effect. In enzymatically dissociated left ventricular myocytes loaded with the Ca2+ probe indo-1, the positive inotropic effect of EMD 54622 occurred with no change in the amplitude of the cytosolic [Ca2+] (Ca(i)) transient. In contrast, both EMD 53998 and EMD 54650 enhanced Ca(i) transient and twitch contraction amplitudes. Length-indo-1 fluorescence relations were analyzed to determine the effects of the three substances on myofilament responsiveness to Ca2+. EMD 54622 enhanced and EMD 54650 had no effect on myofilament responsiveness to Ca2+. Less uniform results were obtained with EMD 53998 (in two of five cells the myofilament responsiveness to Ca2+ was increased, whereas in three other cells it was unaltered). Our results indicate that structural changes in the diazinone molecule shift the mechanism of action for the positive inotropic effect of the diazinone derivatives in the intact cell from a predominant myofilament sensitization (EMD 54622) to an enhancement in cell Ca2+ loading and an augmentation in the Ca(i) transient (EMD 54650). C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 37 TC 43 Z9 43 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN PY 1992 VL 70 IS 6 BP 1081 EP 1090 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA HV923 UT WOS:A1992HV92300001 PM 1533576 ER PT J AU SHAI, SY FISHEL, RS MARTIN, BM BERK, BC BERNSTEIN, KE AF SHAI, SY FISHEL, RS MARTIN, BM BERK, BC BERNSTEIN, KE TI BOVINE ANGIOTENSIN CONVERTING ENZYME CDNA CLONING AND REGULATION - INCREASED EXPRESSION DURING ENDOTHELIAL-CELL GROWTH ARREST SO CIRCULATION RESEARCH LA English DT Article DE CDNA; CLONING; DNA; RNASE PROTECTION ID RIBONUCLEIC-ACID; RAT LUNG; INHIBITORS; INDUCTION; CULTURE; MOUSE; RNA AB Angiotensin converting enzyme (ACE) is a zinc-containing dipeptidase that converts angiotensin I to angiotensin II, a powerful vasoconstrictor and smooth muscle growth factor. ACE activity has been shown to be dynamically regulated by hormones, ACE inhibitors, and endothelial cell growth state. To study how ACE expression is regulated, we isolated and sequenced the bovine ACE gene using both ACE-specific cDNA and genomic clones. Bovine ACE cDNA encodes a single polypeptide of 1,306 residues with a molecular mass of 150 kd. Bovine ACE is approximately 80% homologous to that of other species. lt contains two homologous domains of equal size. Alignment of ACE sequences from bovine, human, mouse, and rabbit reveals that during evolution both domains have been highly conserved. We used the bovine ACE cDNA to study regulation of ACE gene expression during density-dependent growth arrest. As endothelial cells became growth-arrested (6 days after confluence), there was a 12-fold increase in ACE activity and a 90% decrease in DNA synthesis. Immunocytochemically detectable ACE markedly increased in growth-arrested cells. The increase in ACE was due to increased ACE gene expression, as assayed by RNase protection, which showed a 20-fold increase in ACE-specific mRNA. The present study shows that bovine ACE is highly regulated by endothelial cell growth state at the level of protein and mRNA expression. Such dynamic regulation may have important consequences for angiotensin II production during endothelial cell proliferation after arterial injury. C1 EMORY UNIV,SCH MED,DEPT PATHOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT MED,ATLANTA,GA 30322. ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD. FU NIDDK NIH HHS [DK-39777] NR 35 TC 59 Z9 62 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN PY 1992 VL 70 IS 6 BP 1274 EP 1281 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA HV923 UT WOS:A1992HV92300022 PM 1315639 ER PT J AU GERBERDING, JL HENDERSON, DK AF GERBERDING, JL HENDERSON, DK TI MANAGEMENT OF OCCUPATIONAL EXPOSURES TO BLOODBORNE PATHOGENS - HEPATITIS-B VIRUS, HEPATITIS-C VIRUS, AND HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ZIDOVUDINE PROPHYLAXIS; IMMUNE GLOBULIN; FINAL REPORT; TRANSMISSION; 3'-AZIDO-3'-DEOXYTHYMIDINE; SUPPRESSION; HIV-1; RISK; AIDS AB Being a health care worker in today's world is not without risks. Accidental exposure to blood carries with it a definite risk of transmission of infection by various bloodborne pathogens, especially the hepatitis B, hepatitis C, and human immunodeficiency viruses. While infectious disease specialists, hospital epidemiologists, and infection control clinicians can develop many important strategies to reduce this risk-aggressive training, utilization of safer needles, identification of high-risk activities, and efficient disposal systems-their overriding responsibility is to design and implement a comprehensive plan for expeditiously and effectively dealing with accidental exposures when they occur. Among other things, the plan must address a number of key issues, including testing, administering postexposure prophylaxis, providing short- and long-term follow-up care, and, particularly, counseling for helping the health care worker deal with the tremendous anxiety associated with the injury. Drs. Julie L. Gerberding of the University of California, San Francisco, and San Francisco General Hospital and David K. Henderson of the National Institutes of Health and the Warren G. Magnuson Clinical Center have both made significant contributions in this area; in this month's AIDS Commentary they discuss the essential elements of such a plan. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP GERBERDING, JL (reprint author), SAN FRANCISCO GEN HOSP,MED SERV 5H-22,1001 POTRERO AVE,SAN FRANCISCO,CA 94110, USA. NR 31 TC 61 Z9 61 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1992 VL 14 IS 6 BP 1179 EP 1185 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HW264 UT WOS:A1992HW26400002 PM 1623073 ER PT J AU WEINBERGER, M BERG, SL FEUERSTEIN, IM PIZZO, PA WITEBSKY, FG AF WEINBERGER, M BERG, SL FEUERSTEIN, IM PIZZO, PA WITEBSKY, FG TI DISSEMINATED INFECTION WITH MYCOBACTERIUM-GORDONAE - REPORT OF A CASE AND CRITICAL-REVIEW OF THE LITERATURE SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACQUIRED IMMUNODEFICIENCY SYNDROME; PULMONARY INFECTION; ATYPICAL MYCOBACTERIA; PERITONEAL PATHOGEN; PATIENT; PSEUDOINFECTION; SPECIMENS AB Mycobacterium gordonae is only rarely a cause of infection despite its ubiquity in the environment. We describe an 11-year-old girl with disseminated infection due to M. gordonae whose course was complicated by renal failure requiring hemodialysis but who recovered after 15 months of chemotherapy. In a literature search we identified 23 additional cases of infection attributed to M. gordonae, with involvement of the lungs (eight), soft tissue (seven), the peritoneal cavity (three), the cornea (one), and with disseminated disease (five patients, including ours). Two patients were infected with human immunodeficiency virus. We assessed the patterns of infection characteristic of each site and the antibiotic sensitivities of the isolates. Adequate documentation of M. gordonae infection (e.g., amount of growth per culture, detection of specific biochemical characteristics, and confirmation of the organism's identity by a reference center) was lacking in many reports. M. gordonae should not automatically be dismissed as a contaminant when isolated from clinical material. Additional studies are required to establish the extent of this organism's pathogenic role. C1 NIH,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C385,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT RADIOL,WASHINGTON,DC 20057. NR 47 TC 61 Z9 63 U1 0 U2 4 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 JUN PY 1992 VL 14 IS 6 BP 1229 EP 1239 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HW264 UT WOS:A1992HW26400008 PM 1623079 ER PT J AU EASTELL, R VIEIRA, NE YERGEY, AL WAHNER, HW SILVERSTEIN, MN KUMAR, R RIGGS, BL AF EASTELL, R VIEIRA, NE YERGEY, AL WAHNER, HW SILVERSTEIN, MN KUMAR, R RIGGS, BL TI PERNICIOUS-ANEMIA AS A RISK FACTOR FOR OSTEOPOROSIS SO CLINICAL SCIENCE LA English DT Article DE BONE DENSITY; OSTEOCALCIN; OSTEOPOROSIS; PERNICIOUS ANEMIA ID BONE-MINERAL DENSITY; CALCIUM-ABSORPTION; LIQUID-CHROMATOGRAPHY; DIETARY CALCIUM; L-THYROXINE; SERUM; WOMEN; MASS; ACHLORHYDRIA; RATES AB 1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51-76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51-79 years). 2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P<0.001). 3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r=0.61, P<0.01). 4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. 5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism vet to be identified. C1 MAYO CLIN & MAYO FDN,NEPHROL RES UNIT,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,ENDOCRINE RES UNIT,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DIAGNOST NUCL MED SECT,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DIV HEMATOL & INTERNAL MED,ROCHESTER,MN 55905. NICHHD,METAB ANAL & MASS SPECT SECT,BETHESDA,MD 20892. RI Eastell, Richard/G-5851-2011 OI Eastell, Richard/0000-0002-0323-3366 FU NCRR NIH HHS [RR-00585]; NIA NIH HHS [AG-04875]; NIDDK NIH HHS [R01 DK025409, R01 DK058546] NR 49 TC 35 Z9 35 U1 0 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD JUN PY 1992 VL 82 IS 6 BP 681 EP 685 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HY225 UT WOS:A1992HY22500013 PM 1320549 ER PT J AU RUCHKIN, DS JOHNSON, R GRAFMAN, J CANOUNE, H RITTER, W AF RUCHKIN, DS JOHNSON, R GRAFMAN, J CANOUNE, H RITTER, W TI DISTINCTIONS AND SIMILARITIES AMONG WORKING-MEMORY PROCESSES - AN EVENT-RELATED POTENTIAL STUDY SO COGNITIVE BRAIN RESEARCH LA English DT Article DE EVENT-RELATED POTENTIAL; SLOW WAVE; WORKING MEMORY; SHORT-TERM MEMORY; VISUOSPATIAL SKETCH PAD; ARTICULATORY REHEARSAL ID SHORT-TERM-MEMORY; MENTAL ROTATION; VISUAL MEMORY; FACES; INTERFERENCE; IMAGERY; MODELS AB Working memory has been conceptualized as consisting of a number of components, such as an articulatory loop for rehearsing verbal material, a visuo-spatial sketch pad for maintaining visual images and a central executive that controls which information is made available for conscious processing. We recorded event-related brain potentials (ERPs) from normal human subjects while they maintained either visuo-spatial or phonological material in short-term memory for a 5-s interval. The results indicated that specialized brain systems for short-term storage of phonological and visuo-spatial information could be identified on the basis of marked differences between the topographies and morphologies of the ERP components elicited during these two types of short-term memory. The differences emerged during early encoding stages and continued through later retention stages. C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. CUNY HERBERT H LEHMAN COLL,DEPT PSYCHOL,BRONX,NY 10468. RP RUCHKIN, DS (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201, USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 36 TC 157 Z9 164 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD JUN PY 1992 VL 1 IS 1 BP 53 EP 66 DI 10.1016/0926-6410(92)90005-C PG 14 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA MU331 UT WOS:A1992MU33100003 ER PT J AU FRIEDMAN, RB HADLEY, JA AF FRIEDMAN, RB HADLEY, JA TI LETTER-BY-LETTER SURFACE ALEXIA SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID WORD RECOGNITION; READING ALOUD; AGRAPHIA; DYSLEXIA; ACTIVATION; LEXICON AB Patterson and Kay (1982) described two cases of letter-by-letter readers who also appeared to display the symptoms of surface alexia. Both of these patients suffered damage to the occipital and temporal lobes of the left hemisphere subsequent to haematomas. Two possible accounts of these patients' dual alexias were put forward. Each of these accounts was based upon a model that posits separate orthographic lexicons for reading and spelling. The current paper describes a patient who developed letter-by-letter reading and the symptoms of surface alexia following a left-hemisphere infarct in the territory of the posterior cerebral artery. The differences between this case and those reported by Patterson and Kay are discussed, and a third possible account of this combination of alexias, based upon a model that posits one shared orthographic lexicon, is presented. RP FRIEDMAN, RB (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5C-422,BETHESDA,MD 20892, USA. NR 33 TC 40 Z9 41 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0264-3294 J9 COGNITIVE NEUROPSYCH JI Cogn. Neuropsychol. PD JUN PY 1992 VL 9 IS 3 BP 185 EP 208 DI 10.1080/02643299208252058 PG 24 WC Psychology; Psychology, Experimental SC Psychology GA HY308 UT WOS:A1992HY30800001 ER PT J AU WRIGHT, JT CUTTER, GR DASANAYAKE, AP MACSTILES, H CAUFIELD, PW AF WRIGHT, JT CUTTER, GR DASANAYAKE, AP MACSTILES, H CAUFIELD, PW TI EFFECT OF CONVENTIONAL DENTAL RESTORATIVE TREATMENT ON BACTERIA IN SALIVA SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE DENTAL CARIES; LACTOBACILLI; MUTANS STREPTOCOCCI; RESTORATIVE TREATMENT ID HUMAN FISSURE DECAY; STREPTOCOCCUS-MUTANS; S-MUTANS; PROPHYLAXIS; PREVALENCE AB Dental caries results from the dissolution of mineralized dental tissues by the metabolic by-products of oral bacteria colonizing the surface of teeth. The principal modality for dealing with this infectious process is through restorative treatment which removes the pathologic tissue and replaces it with a variety of inert materials. The purpose of this study was to evaluate the effect of traditional restorative treatment on select oral bacterial populations. Fifty-two females demonstrating high levels of mutans streptococci (greater-than-or-equal-to 2.5 x 10(4) colony forming units (cfu) per ml saliva) with no more than four missing posterior teeth were recruited for this study. Salivary levels of mutans streptococci, lactobacilli, total streptococci, and total cultivable bacteria were evaluated before, during, and after restorative treatment. Initial DMFS scores were established by two standardized examiners using bitewing radiographs and clinical examination. which was conducted under optimal conditions. All restorative treatment was completed by faculty members of the University of Alabama School of Dentistry using treatment plans developed by the DMFS examiners. The participants received a mean of 16.4 restored surfaces. which resulted in significant reductions of all the bacterial populations tested. All microbial populations monitored were predicted to return to their baseline levels within 151 days after restorative treatment in 50% of the participants. This study shows that conventional restorative treatment results in a significant reduction of bacterial populations including those associated with the dental caries process, i.e., mutans streptococci and lactobacilli. Although restorative treatment is essential for replacing form and function to the dentition. it does not appear to have a prolonged effect on any of the salivary bacterial populations monitored. including those thought responsible for dental caries. Ideally comprehensive treatment of dental caries should address the infectious nature of this disease through modalities directed at controlling bacterial colonization as well as restoring the afflicted dentition. C1 UNIV ALABAMA,SCH DENT,UNIV STN,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH PUBL HLTH,UNIV STN,BIRMINGHAM,AL 35294. NIH,DIV RES GRANTS,BETHESDA,MD 20892. FU NIDCR NIH HHS [DE-42552 RFP-5-83-3R] NR 21 TC 26 Z9 27 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD JUN PY 1992 VL 20 IS 3 BP 138 EP 143 DI 10.1111/j.1600-0528.1992.tb01548.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA HX294 UT WOS:A1992HX29400007 PM 1623705 ER PT J AU HAASCH, ML SUTHERLAND, LA WEJKSNORA, PJ LECH, JJ AF HAASCH, ML SUTHERLAND, LA WEJKSNORA, PJ LECH, JJ TI EFFECT OF ACRYLAMIDE MONOMER ON HEPATIC CYP1A1 MONOOXYGENASE INDUCTION IN RAINBOW-TROUT SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Article ID BETA-NAPHTHOFLAVONE; O-DEALKYLATION; CYTOCHROME-P-450; PROTEIN; ISOZYME; AGENTS; DNA; MICROSOMES AB 1. Rainbow trout hepatic microsomes were pre-incubated in vitro with 1 pM, 1 nM, and 1- mu-M acrylamide for 20 or 30 min and ethoxyresorufin-O-deethylase (EROD) was measured. In vitro preincubation did not produce a significant decrease in EROD catalytic activity. 2. The effects of 50 ppm acrylamide monomer on hepatic CYP1A1 mRNA and CYP1A1 isozyme steady state levels in rainbow trout were determined after 6, 10, and 14 days of exposure. 3. Acrylamide monomer produced a 35% increase, 51% decrease and 140% increase in CYP1A1 mRNA at 6, 10 and 14 days, respectively, while at the same time CYP1A1 isozyme levels were decreased 12%, 67%, and 62% and EROD activity was decreased 33%, 90%, and 86%, respectively. 4. This indicates that acrylamide treatment may result in either a change in the translation of CYP1A1 mRNA or an isozyme selective inactivation of CYP1A1 resulting in loss of CYP1A1 apoprotein. 5. The effect of acrylamide treatment on hepatic CYP1A1 induction was determined using 10 or 14 day treatment with 50 ppm acrylamide monomer in a flowthrough exposure and induction with beta-naphthoflavone (beta-NF; 100 mg/kg i.p.) for 1 or 4 days. 6. Acrylamide and 1-day beta-NF had no effect on CYP1A1 mRNA levels when compared to 1-day beta-NF treatment alone, but acrylamide and 4-day beta-NF resulted in a 74% decrease in CYP1A1 mRNA compared to 4-day beta-NF treatment alone. 7. This indicates that while the initial induction response (1-day) to beta-NF is not affected by acrylamide treatment, the full induction response over 4 days was inhibited by acrylamide due to decreased CYP1A1 mRNA levels. possibly by effects of acrylamide and/or a metabolite(s) on the transcription of CYP1A1 mRNA or by decreasing the stability of CYP1A1 mRNA. C1 MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,8701 WATERTOWN PLANK RD,MILWAUKEE,WI 53226. UNIV WISCONSIN,NIEHS,MARINE FRESHWATER BIOMED RES CORE CTR,MILWAUKEE,WI 53204. LAPHAM HALL UNIV,DEPT BIOL SCI,MILWAUKEE,WI 53201. FU NIEHS NIH HHS [ES 01080, ES 04184] NR 31 TC 6 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD JUN PY 1992 VL 102 IS 2 BP 281 EP 286 DI 10.1016/0742-8413(92)90112-K PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA JC670 UT WOS:A1992JC67000009 PM 1358542 ER PT J AU SHIN, DG LEE, CH ZHANG, JH RUDD, KE BERG, CM AF SHIN, DG LEE, CH ZHANG, JH RUDD, KE BERG, CM TI REDESIGNING, IMPLEMENTING AND INTEGRATING ESCHERICHIA-COLI GENOME SOFTWARE TOOLS WITH AN OBJECT-ORIENTED DATABASE SYSTEM SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID MAP AB This paper reports our exploratory work to redesign, implement and integrate a collection of genome software tools with an object-oriented database system. Our software tools deal with genome data from Escherichia coli K-12, a bacterium that has been studied intensively and provides richer data sets than any other living organism. The object-oriented DBMS used for the integration is ONTOS, a commercial object-oriented system from Ontologic Inc. This redesign and implementation task was performed in two steps. First, C programs were converted into C++, and then the C++ version programs were modified and integrated with an object-oriented modeling of the data to form an ONTOS database application. The first step helps us develop a conceptual view for a DBMS-independent object-oriented construct. The second step elucidates what additional DBMS-dependent modification steps are needed to provide persistency to the objects. Examples are included to illustrate steps of the redesign and implementation. Overall, the outcome of this project demonstrates that programs and data can be successfully integrated with an object-oriented database, while providing the objects with persistency and shareability. This paper includes discussions using concrete examples on what advantage the object-oriented database approach provides over the relational database approach. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL,BETHESDA,MD 20894. UNIV CONNECTICUT,DEPT MOLEC & CELL BIOL,STORRS,CT 06269. RP SHIN, DG (reprint author), UNIV CONNECTICUT,DEPT COMP SCI & ENGN,STORRS,CT 06269, USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUN PY 1992 VL 8 IS 3 BP 227 EP 238 PG 12 WC Computer Science, Interdisciplinary Applications SC Computer Science GA HY586 UT WOS:A1992HY58600003 PM 1633564 ER PT J AU CHEN, JH LE, SY MAIZEL, JV AF CHEN, JH LE, SY MAIZEL, JV TI A PROCEDURE FOR RNA PSEUDOKNOT PREDICTION SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID MOSAIC-VIRUS RNA; MESSENGER-RNA; REGION; SECONDARY; STABILITY; PRINCIPLE AB The RNA pseudoknot has been proposed as a significant structural motif in a wide range of biological processes of RNAs. A pseudoknot involves intramolecular pairing of bases in a hairpin loop with bases outside the stem of the loop to form a second stem and loop region. In this study, we propose a method for searching and predicting pseudoknots that are likely to have functional meaning. In our procedure, the orthodox hairpin structure involved in the pseudoknot is required to be both statistically significant and relatively stable to the others in the sequence. The bases outside the stem of the hairpin loop in the predicted pseudoknot are not entangled with any formation of a highly stable secondary structure in the sequence. Also, the predicted pseudoknot is significantly more stable than those that can be formed from a large set of scrambled sequences under the assumption that the energy contribution from a pseudoknot is proportional to the size of second loop region and planar energy contribution from second stem region. A number of functional pseudoknots that have been reported before can be identified and predicted from their sequences by our method. C1 NCI,DIV CANC BIOL & DIAG,MATH BIOL LAB,FREDERICK,MD 21702. NATL RES COUNCIL CANADA,INST BIOL SCI,OTTAWA K1A 0R6,ONTARIO,CANADA. RP CHEN, JH (reprint author), NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,ADV SCI COMP LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 23 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUN PY 1992 VL 8 IS 3 BP 243 EP 248 PG 6 WC Computer Science, Interdisciplinary Applications SC Computer Science GA HY586 UT WOS:A1992HY58600005 PM 1378773 ER PT J AU CUNNION, RE AF CUNNION, RE TI CLINICAL-TRIALS OF IMMUNOTHERAPY FOR SEPSIS SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE IMMUNOGLOBULINS; SHOCK, SEPTIC; GRAM-NEGATIVE BACTERIA; ENDOTOXINS; MONOCLONAL ANTIBODIES; PATIENT OUTCOME ASSESSMENT; MORTALITY; CRITICAL CARE RP CUNNION, RE (reprint author), NIH,BLDG 10,ROOM 7-D-43,BETHESDA,MD 20892, USA. NR 6 TC 8 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 1992 VL 20 IS 6 BP 721 EP 723 DI 10.1097/00003246-199206000-00001 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA HX520 UT WOS:A1992HX52000001 PM 1597020 ER PT J AU BOULAY, JL PAUL, WE AF BOULAY, JL PAUL, WE TI THE INTERLEUKIN-4 FAMILY OF LYMPHOKINES SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID EOSINOPHIL DIFFERENTIATION FACTOR; CYTOKINE RECEPTOR SUPERFAMILY; GROWTH-FACTOR RECEPTORS; GM-CSF; HUMAN CHROMOSOME-5; NUCLEOTIDE-SEQUENCE; MYELOID DISORDERS; MOLECULAR-CLONING; GENE-CLUSTER; CELL-LINES AB Evidence has accumulated indicating that four T-cell derived lymphokines, interleukin-4, interleukin-5, granulocyte-macrophage colony stimulating factor and interleukin-3, are closely related. The genes encoding these lymphokines are clustered within a region of 1000kb, the proteins have a common secondary and spatial organization, and their corresponding receptors are all members of the hemopoietin family of receptors. RP BOULAY, JL (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 45 TC 53 Z9 56 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 JUN PY 1992 VL 4 IS 3 BP 294 EP 298 DI 10.1016/0952-7915(92)90079-T PG 5 WC Immunology SC Immunology GA JD797 UT WOS:A1992JD79700009 PM 1418708 ER PT J AU SALUSTRI, A YANAGISHITA, M UNDERHILL, CB LAURENT, TC HASCALL, VC AF SALUSTRI, A YANAGISHITA, M UNDERHILL, CB LAURENT, TC HASCALL, VC TI LOCALIZATION AND SYNTHESIS OF HYALURONIC-ACID IN THE CUMULUS CELLS AND MURAL GRANULOSA-CELLS OF THE PREOVULATORY FOLLICLE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; OOCYTE COMPLEX; MOUSE OOCYTES; RAT; INVITRO; EXPANSION; BINDING; DIFFERENTIATION C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT ANAT & CELL BIOL,WASHINGTON,DC 20007. UNIV UPPSALA,DEPT MED & PHYSIOL CHEM,S-75123 UPPSALA,SWEDEN. RP SALUSTRI, A (reprint author), UNIV ROME 2,FAC MED,DEPT SANITA PUBBL & BIOL CELLULARE,I-00173 ROME,ITALY. OI SALUSTRI, ANTONIETTA/0000-0002-8731-1041 FU NHLBI NIH HHS [HL 401565]; NICHD NIH HHS [HD 26758] NR 36 TC 136 Z9 137 U1 2 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 JUN PY 1992 VL 151 IS 2 BP 541 EP 551 DI 10.1016/0012-1606(92)90192-J PG 11 WC Developmental Biology SC Developmental Biology GA HY740 UT WOS:A1992HY74000020 PM 1601185 ER PT J AU GIRI, PR MARIETTA, CA HIGUCHI, S KINCAID, RL AF GIRI, PR MARIETTA, CA HIGUCHI, S KINCAID, RL TI MOLECULAR AND PHYLOGENETIC ANALYSIS OF CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE (CALCINEURIN) CATALYTIC SUBUNIT GENES SO DNA AND CELL BIOLOGY LA English DT Article ID BINDING PROTEINS; BRAIN; PHOSPHODIESTERASE; PHOSPHORYLATION; IDENTIFICATION; PURIFICATION; EXPRESSION; ANTIBODIES; ISOFORMS; CLONING AB In the mammalian brain, there are multiple catalytic subunits for the Ca2+- and calmodulin-dependent protein phosphatase [also called protein phosphatase 2B (PP-2B) and calcineurin] that are derived from two structural genes. The coding sequences of these two genes are distinguished by the absence (PP2B-alpha-1) or the presence (PP2B-alpha-2) of an amino terminus containing polyproline. Both of these genes can produce intragenic isoforms through alternative splicing. In the present study, a potential phylogenetic relationship of these genes was inferred from analysis of genomic DNA and from studies of mRNA and protein expression. Southern blot analysis showed unique restriction fragments for both genes in seven mammalian species; however, in organisms from two nonmammalian vertebrates (chicken and lizard), hybridization was observed only for PP2B-alpha-1. In agreement with these results, Northern blots of mammalian brain RNA showed transcripts for both genes, with about two to three times more of the PP2B-alpha-1 mRNAs, whereas in chicken and lizard, only PP2B-alpha-1 transcripts were detected. An analysis of protein expression by two-dimensional electrophoresis was also consistent with these findings. For the purified mammalian brain protein, eight to ten variants were observed with isoelectric points of 5.2-5.8; immunoblot analysis using anti-peptide antibodies indicated that the majority of these were PP2B-alpha-1 forms. In chicken brain, multiple isoforms were recognized by antibodies against the PP2B-alpha-1 forms, but no reactivity was seen with those against the PP2B-alpha-2 forms. Taken together, these findings suggest that: (i) in mammals, the predominant catalytic subunit isoforms in brain are PP2B-alpha-1 products and (ii) the gene for the polyproline-containing catalytic subunit of calmodulin-dependent phosphatase (PP2B-alpha-2) may have evolved after the avian/reptilian branching point, perhaps to carry out a role(s) of particular significance in mammals. RP GIRI, PR (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,IMMUNOL SECT,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 37 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 1992 VL 11 IS 5 BP 415 EP 424 DI 10.1089/dna.1992.11.415 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA JH634 UT WOS:A1992JH63400008 PM 1318721 ER PT J AU PICKENS, RW JOHANSON, CE AF PICKENS, RW JOHANSON, CE TI CRAVING - CONSENSUS OF STATUS AND AGENDA FOR FUTURE-RESEARCH SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE CRAVING; DETERMINANTS OF DRUG ABUSE; DETERMINANTS OF RELAPSE; RESEARCH AGENDA ID ABSTINENCE; SMOKING AB The term craving is used frequently in relationship to drug abuse and its treatment but there is disagreement over its definition and role. In February 1991, a meeting of experts from several disciplines, sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse, was convened with the goal of reaching consensus about the importance of craving and to suggest a future research program. The participants agreed that craving is a subjective state in humans that is associated with drug dependence but little is known about its determinants, relationship to drug taking, and measurement. To advance our knowledge, a substantial research program is required. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RP PICKENS, RW (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA06030, DA06175] NR 5 TC 120 Z9 121 U1 1 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 JUN PY 1992 VL 30 IS 2 BP 127 EP 131 DI 10.1016/0376-8716(92)90017-7 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA JB721 UT WOS:A1992JB72100004 PM 1633752 ER PT J AU CLEVENGER, CV SILLMAN, AL HANLEYHYDE, J PRYSTOWSKY, MB AF CLEVENGER, CV SILLMAN, AL HANLEYHYDE, J PRYSTOWSKY, MB TI REQUIREMENT FOR PROLACTIN DURING CELL-CYCLE REGULATED GENE-EXPRESSION IN CLONED LYMPHOCYTES-T SO ENDOCRINOLOGY LA English DT Article ID NB2 LYMPHOMA-CELLS; DNA-SYNTHESIS; HELPER LYMPHOCYTE; ADRENAL-CORTEX; G-PROTEINS; RECEPTOR; GROWTH; INTERLEUKIN-2; CLONING; CDNA AB The neuroendocrine hormone PRL acts as a progression factor during interleukin-2 (IL2) stimulated lymphocyte proliferation. Since the sequential expression of cell cycle regulated genes occurs during this process, we examined the contribution of IL2 and PRL to specific RNA accumulation. Stimulation of the cloned T cell line L2 with IL2 and PRL induced the sequential expression of interferon regulatory factor-1, c-myc, proliferating cell nuclear antigen, thymidine kinase, cyclin B, and histone H3. Stimulation of L2 cells with PRL alone, however, induced only the expression of interferon regulatory factor-1. Depletion of PRL, through the use of an anti-PRL antiserum, inhibited IL2 driven proliferation and the expression of cyclin B and histone H3. These results demonstrate that PRL may regulate T cell proliferation by enhancing the expression of some genes necessary for entry into S-phase. C1 NCI, GENET LAB, BETHESDA, MD 20892 USA. RP UNIV PENN, DEPT PATHOL & LAB MED, 545 CLIN RES BLDG, 422 CURIE BLVD, PHILADELPHIA, PA 19104 USA. FU NIGMS NIH HHS [GM-13901, GM-36962] NR 58 TC 81 Z9 81 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3216 EP 3222 DI 10.1210/en.130.6.3216 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300016 PM 1534539 ER PT J AU CHIN, E ZHOU, J BONDY, C AF CHIN, E ZHOU, J BONDY, C TI ANATOMICAL RELATIONSHIPS IN THE PATTERNS OF INSULIN-LIKE GROWTH-FACTOR (IGF)-I, IGF BINDING PROTEIN-1, AND IGF-I RECEPTOR GENE-EXPRESSION IN THE RAT-KIDNEY SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; TISSUE CONCENTRATIONS; RENAL HYPERTROPHY; SOMATOMEDIN-C; CELLS; PARACRINE; INCREASES; DISTINCT; MICE AB The rat kidney is both a target of circulating insulin-like growth factor-I (IGF-I) and a site of local IGF-I production. In order to identify which renal structures produce IGF-I and the functionally related IGF binding protein 1 (IGFBP-1), and which structures are potential sites of circulating or endogenous renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP-1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF-I receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are both localized in the epithelial cells of medullary thick ascending limbs (TALs) of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant in TALs, but, in addition, is distributed throughout the distal nephron and collecting duct, and in the glomerulus, with lowest levels found in proximal tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I receptor mRNA levels were not significantly effected by either treatment. However, the most dramatic effect produced by the interruption of the pituitary-renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene expression in individual kidneys and even in individual nephrons, suggesting a local interaction between IGF-I and IGFBP-1 in the regulation of their respective mRNA levels. Functional implications issuing from these anatomical relationships in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP-1, may act on luminal TAL and downstream receptor sites. The specific physiological role of IGF-I produced in TALs is open to speculation. Glomerular IGF-I receptor sites, based on their localization upstream and distant from local sources of IGF-I production, are predicted to be targets for circulating IGFs. RP CHIN, E (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10-10N262, BETHESDA, MD 20892 USA. NR 37 TC 86 Z9 86 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3237 EP 3245 DI 10.1210/en.130.6.3237 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300019 PM 1375897 ER PT J AU LEBON, TR KASUYA, J PAXTON, RJ BELFRAGE, P HOCKMAN, S MANGANIELLO, VC FUJITAYAMAGUCHI, Y AF LEBON, TR KASUYA, J PAXTON, RJ BELFRAGE, P HOCKMAN, S MANGANIELLO, VC FUJITAYAMAGUCHI, Y TI PURIFICATION AND CHARACTERIZATION OF GUANOSINE 3',5'-MONOPHOSPHATE-INHIBITED LOW K(M)-ADENOSINE 3',5'-MONOPHOSPHATE PHOSPHODIESTERASE FROM HUMAN PLACENTAL CYTOSOLIC FRACTIONS SO ENDOCRINOLOGY LA English DT Article ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; KM CAMP PHOSPHODIESTERASE; AMP PHOSPHODIESTERASE; ADIPOSE-TISSUE; FAT-CELLS; MICROSEQUENCE ANALYSIS; RAT-LIVER; INSULIN; PROTEINS; PHOSPHORYLATION AB We previously characterized human placental cytosolic cAMP phosphodiesterase (PDE) and found that two low K(m) cAMP PDE isoforms that were very sensitive to inhibition by cGMP and cilostamide were activated by insulin. As a first step toward understanding the mechanisms by which insulin activates this enzyme, we purified the cGMP-inhibited low K(m) cAMP PDE (cGI-PDE) from human placentas. The enzyme was purified 11,700-fold from a pool of 100,000 x g supernatant fractions of 10-15 placentas by ammonium sulfate precipitation, diethylaminoethyl-cellulose chromatography, and affinity chromatography, using an isothiocyanate derivative of cilostamide (CIT-agarose). The specific activity of the affinity-purified enzyme was 432 +/- 17 nmol/min.mg (mean +/- SD; n = 4). Gel permeation chromatography of the CIT-agarose eluates revealed one protein peak that coincided with PDE activity at an elution position of 135,000 daltons. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of this protein peak and CIT-agarose eluates revealed the same patterns, indicating that the purified PDE preparations contained multiple proteins with apparent mol wt of 138K, 83K, 72K, 67K, 63K, and 44K. The 138K form appears to be an intact enzyme; an analogous approximately 135K form has recently been identified in rat adipocyte particulate fractions by specific immunoprecipitation or Western immunoblots. In addition, other smaller forms eluted at 135,000 daltons on gel permeation chromatography, suggesting that, although proteolyzed, they must have been associated by either noncovalent interactions or disulfide bonds. All of the protein bands observed on the sodium dodecyl sulfate-polyacrylamide electrophoresis gel reacted with rabbit antibodies raised against human platelet cGI-PDE. Ten peptides from endoproteinase Lys-C-digests of the affinity-purified placental cGI-PDE were isolated and sequenced; sequences of eight peptides were identical to the deduced amino acid sequences in the C-terminal half of a human heart cGI-PDE cDNA, while those of two peptides were not found in the heart enzyme. The sequences of the eight peptides also matched peptide sequences derived from a purified human platelet cGI-PDE. These results provide evidence that the catalytic C-terminal half domain of the placental insulin-sensitive cGI-PDE shares homology with those of human heart and platelet cGI-PDEs. K(m) and maximum velocity values for cAMP and cGMP were 0.57-mu-M and 862 nmol/min.mg, and 15-mu-M and 467 nmol/min.mg, respectively. ED50 values for cGMP, cilostamide, and Ro 20-1724 were 0.12, 0.22, and 120-mu-M, respectively. The results suggest that although human placental cGI-PDE is closely related to previously characterized cGI-PDEs, there are subtle differences in specific activity, susceptibility to proteases, and inhibitor sensitivity. C1 CITY HOPE NATL MED CTR, BECKMAN RES INT, DEPT MOLEC GENET, 1450 E DUARTE RD, DUARTE, CA 91010 USA. CITY HOPE NATL MED CTR, BECKMAN RES INT, DIV IMMUNOL, DUARTE, CA 91010 USA. UNIV LUND, DEPT PHYSIOL CHEM, S-22101 LUND, SWEDEN. NHLBI, CELLULAR METAB LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA-33572]; NIDDK NIH HHS [DK-29770] NR 28 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3265 EP 3274 DI 10.1210/en.130.6.3265 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300022 PM 1317779 ER PT J AU DAS, SK FLANDERS, KC ANDREWS, GK DEY, SK AF DAS, SK FLANDERS, KC ANDREWS, GK DEY, SK TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS (BETA-2 AND BETA-3) IN THE MOUSE UTERUS - ANALYSIS OF THE PERIIMPLANTATION PERIOD AND EFFECTS OF OVARIAN-STEROIDS SO ENDOCRINOLOGY LA English DT Article ID CELL-ADHESION RECEPTORS; SMOOTH-MUSCLE CELLS; SEQUENCE-ANALYSIS; GENE-EXPRESSION; 1ST TRIMESTER; CDNA CLONING; TGF-BETA; PRECURSOR; ESTROGEN; RAT AB Expression of beta-type transforming growth factor genes (TGF-beta-2 and TGF-beta-3) in the mouse uterus during the periimplantation period and in response to an acute exposure to 17-beta-estradiol (E2) and progesterone (P4) was studied using Northern blot hybridization and/or immunocytochemistry. Polyclonal antipeptide antibodies specific for TGF-beta-2 or TGF-beta-3 were employed for immunocytochemistry. In the preimplantation uterus [days (D) 1-4 of pregnancy; day 1 = vaginal plug], immunostaining for TGF-beta-2 was observed in luminal and glandular epithelia as well as in myometrium and vascular smooth muscle. In the postimplantation period (D5-D8), TGF-beta-2 immunostaining was also detected in decidual cells. In contrast, TGF-beta-3 immunostaining was restricted to the myometrium and vascular smooth muscle throughout the periimplantation period (D1-D8). Antisense TGF-beta-2 and TGF-beta-3 RNA probes were employed for Northern blotting. Northern blot hybridization revealed four TGF-beta-2 transcripts (approximately 6.0, 5.0, 4.0, and 3.5 kilobases) in total uterine poly(A)+ RNA on D1-D6 and in poly(A)+ RNA from the deciduum and myometrium collected on D7 and D8 of pregnancy. These TGF-beta-2 transcripts were also detected in isolated samples of deciduomata or myometrium obtained from D8 pseudopregnant mice in which the decidual cell reaction was induced experimentally on D4. The levels of these transcripts remained relatively constant during the periimplantation period. Northern blot analysis detected a 3.8-kilobase TGF-beta-3 transcript in total uterine poly(A)+ RNA on D1-D6. This transcript was detected in myometrial RNA samples on D7 and D8 of pregnancy or D8 of psuedopregnancy, but was not detected in RNA from the deciduum on D7 and D8 or in that from deciduomata on D8. The effects of ovarian steroids on TGF-beta-2 and TGF-beta-3 mRNAs were examined in uteri of adult ovariectomized mice. Uterine TGF-beta-2 or TGF-beta-3 mRNA persisted in ovariectomized mice. However, an injection of E2 induced a rapid (6 h), but transient, induction (approximately 3- to 4-fold) of TGF-beta-2 mRNA. An injection of P4 had no effect on TGF-beta-2 mRNA levels, and coinjection of P4 with E2 did not antagonize the E2-stimulated transient accumulation of TGF-beta-2 mRNA. In comparison, neither an injection of E2 nor one of P4 exerted significant effects on TGF-beta-3 mRNA levels. The results of this study establish that 1) TGF-beta-2 and TGF-beta-3 genes are expressed in the periimplantation uterus; 2) epithelial, myometrial, and decidual cells are primary sites of TGF-beta-2 synthesis, whereas myometrial cells are the primary site of synthesis of TGF-beta-3 during the periimplantation period; and 3) E2 may play a role in the regulation of TGF-beta-2 mRNA levels, but an acute treatment with P4 and/or E2 does not regulate TGF-beta-3 gene expression. The distinct uterine cell type-specific expression of TGF-beta-2 and TGF-beta-3 suggests that these growth factors may have different functional roles during the periimplantation period. C1 UNIV KANSAS, MED CTR,RALPH L SMITH RES CTR,DEPT OBSTET GYNECOL, MRRC 37-317,39TH & RAINBOW BLVD, KANSAS CITY, KS 66160 USA. UNIV KANSAS, MED CTR, RALPH L SMITH RES CTR, DEPT PHYSIOL, KANSAS CITY, KS 66160 USA. UNIV KANSAS, MED CTR, RALPH L SMITH RES CTR, DEPT BIOCHEM & MOLEC BIOL, KANSAS CITY, KS 66160 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-12304]; NIEHS NIH HHS [ES-04725] NR 63 TC 148 Z9 149 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3459 EP 3466 DI 10.1210/en.130.6.3459 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300046 PM 1375903 ER PT J AU SKLAR, MM THOMAS, CL MUNICCHI, G ROBERTS, CT LEROITH, D KIESS, W NISSLEY, P AF SKLAR, MM THOMAS, CL MUNICCHI, G ROBERTS, CT LEROITH, D KIESS, W NISSLEY, P TI DEVELOPMENTAL EXPRESSION OF RAT INSULIN-LIKE GROWTH FACTOR-II/MANNOSE 6-PHOSPHATE RECEPTOR MESSENGER-RIBONUCLEIC-ACID SO ENDOCRINOLOGY LA English DT Article ID FACTOR-II RECEPTOR; MULTIPLICATION-STIMULATING ACTIVITY; IGF-II; BINDING; CELLS; GENE; RNA; SERUM; MANNOSE-6-PHOSPHATE; CHICKEN AB We have examined the developmental pattern of the insulin-like growth factor-II (IGF-II)/mannose 6-phosphate (M6P) receptor mRNA in various rat tissues from 20-day gestation fetuses and 20-day postnatal animals by Northern blotting and solution hybridization/RNase protection assays. The major mRNA species in all fetal and postnatal tissues was 9.0 kilobases. The rank order of receptor mRNA concentrations among the fetal tissues was heart > limb/muscle, lung, intestine, kidney, liver > brain, which agrees with the previously reported rank order of the tissue concentrations of receptor protein. The concentration of IGF-II/M6P receptor mRNA was significantly lower in postnatal tissues, again reflecting the relative levels of receptor protein in fetal and postnatal tissues. We measured IGF-II/M6P receptor mRNA copy number in fetal heart, the tissue with the highest concentration of receptor protein and mRNA, by including in the solution hybridization/RNase protection assay known amounts of a sense strand transcript of the receptor cDNA. This sense strand standared was quantitated by incorporating a tracer amount of [P-32]UTP into the transcript and measuring the radioactivity in the product purified by gel electrophoresis. The receptor mRNA copy number in fetal heart was 74 molecules/cell. We conclude that the IGF-II/M6P receptor mRNA concentration is an important determinant of the level of receptor protein in most tissues. C1 NCI, METAB BRANCH, BLDG 10, ROOM 4N115, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 44 TC 31 Z9 31 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3484 EP 3491 DI 10.1210/en.130.6.3484 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300049 PM 1317785 ER PT J AU SZAPARY, D OSHIMA, H SIMONS, SS AF SZAPARY, D OSHIMA, H SIMONS, SS TI MODULATION OF GLUCOCORTICOID INDUCTION OF STABLY TRANSFECTED TYROSINE AMINOTRANSFERASE GENE CONSTRUCTS INVOLVES ELEMENTS UP-STREAM OF THE GLUCOCORTICOID-RESPONSIVE ELEMENT SO ENDOCRINOLOGY LA English DT Article ID TISSUE-CULTURE CELLS; RAT HEPATOMA-CELLS; DEXAMETHASONE 21-MESYLATE; TRANSCRIPTION FACTORS; BIOLOGICAL-ACTIVITY; AGONIST ACTIVITY; NUCLEAR-BINDING; MESSENGER-RNA; ALBINO LOCUS; RECEPTORS AB Previous studies have documented that the amount of agonist activity expressed by the antiglucocorticoid dexamethasone 21-mesylate (Dex-Mes) for tyrosine aminotransferase (TAT) induction in two rat hepatoma cell lines (Fu5-5 and HTC) is greater in Fu5-5 cells and could be varied in each cell line with changes in cell density. We have proposed that both phenomena are mediated by the binding of a trans-acting factor, the concentration or activity of which is lower in HTC cells. We have now used DNase-I hypersensitivity studies to identify a possible binding site for this factor at around -3.6 kilobases (kb) of the TAT gene. Fu5-5 and HTC cells were then stably transfected with hybrid constructs either with (3.9TATCAT) or without (2.9TATCAT) this region of the TAT gene fused up-stream of a chloramphenicol acetyltransferase (CAT) reporter gene. High levels of Dex-Mes agonist activity for the induction of CAT activity in Fu5-5 cells were seen only with the 3.9TATCAT construct, indicating that the 0.97-kb region unique to this construct controlled the high levels of Dex-Mes agonist activity. Furthermore, variations in Fu5-5 cell density caused major quantitative changes in the amount of Dex-Mes agonist activity only in cells containing the 3.9TATCAT construct, consistent with the same 0.97-kb sequences also controlling the variations in Dex-Mes agonist activity. Additional studies at high and low cell densities revealed that the modulation of Dex-Mes agonist activity for both the endogenous TAT gene and the transfected TAT/CAT gene was not due to changes in the start site of gene transcription. These studies both support our previous hypothesis that modulation of Dex-Mes agonist activity results from changes in a trans-acting factor and localize a necessary cis-acting element to sequences between -3.9 and -2.9 kb of the TAT gene. These studies, thus, define a potentially new element for glucocorticoid regulation of TAT gene transcription. C1 NIDDKD, STEROID HORMONES SECT, BETHESDA, MD 20892 USA. NR 57 TC 29 Z9 28 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3492 EP 3502 DI 10.1210/en.130.6.3492 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300050 PM 1350762 ER PT J AU MATSUMOTO, K GAETANO, C DAUGHADAY, WH THIELE, CJ AF MATSUMOTO, K GAETANO, C DAUGHADAY, WH THIELE, CJ TI RETINOIC ACID REGULATES INSULIN-LIKE GROWTH FACTOR-II EXPRESSION IN A NEUROBLASTOMA CELL-LINE SO ENDOCRINOLOGY LA English DT Article ID NEURO-BLASTOMA CELLS; GENE-EXPRESSION; WILMS TUMOR; RECEPTOR AB Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides that play an important role in normal growth and development. IGF-II has been shown to stimulate the growth of neuroblastoma tumors in an autocrine and paracrine fashion. Critical in determining the role of IGF-II in tumorigenesis is the necessity to delineate factors affecting the transcription of IGF-II in normal and tumor tissues. To date such factors are poorly characterized. In this study we find that retinoic acid (RA), a naturally occurring morphogen, that has been shown to be indispensable in the development of the chick limb bud, stimulates an increase in IGF-II messenger RNA (mRNA) in the Lan-1-15N neuroblastoma cell line. This increase in IGF-II is coincident with RA mediated inhibition of DNA synthesis. An increase in the steady state levels of IGF-II mRNA is detectable within 2 h of RA treatment and maximal by 24 h. In RA-treated Lan-1-15N cells, IGF-II mRNA levels are regulated at the level of new gene transcription and result in an increase in IGF-II protein in the culture supernatant. These studies suggest one mechanism affecting the production of IGF-II in vivo may be mediated by RA and detail a model system by which transcriptional regulation of IGF-II mRNA can be analyzed. C1 NCI, DIV CANC TREATMENT, PEDIAT BRANCH, MOLEC GENET SECT, BETHESDA, MD 20892 USA. WASHINGTON UNIV, SCH MED, DEPT INTERNAL MED, ST LOUIS, MO 63110 USA. OI Gaetano, Carlo/0000-0002-5238-1832 NR 28 TC 34 Z9 34 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1992 VL 130 IS 6 BP 3669 EP 3676 DI 10.1210/en.130.6.3669 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HW763 UT WOS:A1992HW76300071 PM 1375906 ER PT J AU COIN, PG ROGGLI, VL BRODY, AR AF COIN, PG ROGGLI, VL BRODY, AR TI DEPOSITION, CLEARANCE, AND TRANSLOCATION OF CHRYSOTILE ASBESTOS FROM PERIPHERAL AND CENTRAL REGIONS OF THE RAT LUNG SO ENVIRONMENTAL RESEARCH LA English DT Article ID SHORT-TERM EXPOSURE; CROCIDOLITE ASBESTOS; AMOSITE ASBESTOS; PULMONARY MACROPHAGES; SHORT FIBERS; MOUSE LUNG; LONG; FIBROSIS; ACCUMULATION; INHALATION C1 DUKE UNIV,DEPT PATHOL,DURHAM,NC 27706. VET ADM MED CTR,DURHAM,NC 27705. RP COIN, PG (reprint author), NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 50 TC 51 Z9 52 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JUN PY 1992 VL 58 IS 1 BP 97 EP 116 DI 10.1016/S0013-9351(05)80207-5 PG 20 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA HX721 UT WOS:A1992HX72100008 PM 1317793 ER PT J AU MIYAZAWA, M NISHIO, J WEHRLY, K JAY, G MELVOLD, RW CHESEBRO, B AF MIYAZAWA, M NISHIO, J WEHRLY, K JAY, G MELVOLD, RW CHESEBRO, B TI DETAILED MAPPING OF THE RFV-1 GENE THAT INFLUENCES SPONTANEOUS-RECOVERY FROM FRIEND RETROVIRUS-INDUCED LEUKEMIA SO EUROPEAN JOURNAL OF IMMUNOGENETICS LA English DT Note ID LYMPHOCYTE-T RESPONSE; TUMOR NECROSIS FACTOR; LEUKEMIA-VIRUS; IDENTIFICATION; COMPLEX; MICE; H-2D; RESPONSIVENESS; LYMPHOTOXIN; IMMUNITY AB Using H-2 recombinant and mutant mice, the Rfv-1 gene influencing spontaneous recovery from Friend retrovirus (FV)-induced leukaemia was mapped in the D locus. Two D(b) alleles were required for full recovery, and a single D(d) transgene did not convey increased susceptibility to FV in the presence of homozygous D(b/b) genotype. The results suggest that an increase in the expression of D(b) may lead to more effective stimulation of FV-specific CTL. C1 NORTHWESTERN UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,CHICAGO,IL 60611. AMER RED CROSS,JEROME H HOLLAND LAB,VIROL LAB,BETHESDA,MD 20814. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 23 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7420 J9 EUR J IMMUNOGENET JI Eur. J. Immunogenet. PD JUN PY 1992 VL 19 IS 3 BP 159 EP 164 DI 10.1111/j.1744-313X.1992.tb00054.x PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA HX117 UT WOS:A1992HX11700005 PM 1627536 ER PT J AU MURPHY, WJ BENNETT, M ANVER, MR BASELER, M LONGO, DL AF MURPHY, WJ BENNETT, M ANVER, MR BASELER, M LONGO, DL TI HUMAN-MOUSE LYMPHOID CHIMERAS - HOST-VS-GRAFT AND GRAFT-VS-HOST REACTIONS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID COMBINED IMMUNE-DEFICIENCY; IMMUNODEFICIENT SCID MICE; CELLS; LYMPHOCYTES; EXPRESSION; RECEPTOR AB Human peripheral blood lymphocytes (huPBL) were injected into mice with severe combined immune deficiency (SCID). It was ascertained that murine natural killer (NK) cells were capable of affecting engraftment of human lymphocytes in SCID mice. The presence of host NK cells resulted in the clearance of the human lymphocytes. Human T lymphocytes were the primary cell to engraft in the SCID recipients, with human T cells being detected in the spleen, lymph nodes, bone marrow and peritoneal cavity of the mice up to several months after transfer. No human T cells were detected in the murine thymus and the level of engraftment in the periphery could be highly variable. Additionally, there appeared to be significant reactions between the human lymphocytes and the murine host resulting in a xenogeneic graft-vs. -host reaction (XGVHR). The predominant manifestation involved splenomegaly resulting from an expansion of murine hematopoietic cells in the spleens of these xenogeneic chimeras. The severity of the XGVHR could be correlated with the extent of human T cell engraftment and the recovered human T cells were found to be in a proliferative state. Thus, there appear to be significant host-vs.-graft and graft-vs.-host interactions occurring in human/mouse lymphocyte chimeras. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21701. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75230. NCI,LAB ANIM SCI PROGRAM,FREDERICK,MD 21701. NCI,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21701. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 14 TC 109 Z9 108 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 JUN PY 1992 VL 22 IS 6 BP 1421 EP 1427 DI 10.1002/eji.1830220614 PG 7 WC Immunology SC Immunology GA JA024 UT WOS:A1992JA02400013 PM 1534757 ER PT J AU COSTA, PT MCCRAE, RR AF COSTA, PT MCCRAE, RR TI MULTIPLE USES FOR LONGITUDINAL PERSONALITY DATA SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article ID 5-FACTOR MODEL; SELF-REPORTS; NEUROTICISM; DISEASE; CONTINUITY; COMPLAINTS; VALIDATION; ADULTHOOD; STABILITY; INVENTORY AB Most longitudinal studies are designed to serve fairly narrow purposes, such as the prediction of life outcomes from theoretically relevant antecedent variables, or the documentation of age-related changes in the level of personality or cognitive variables. However, the accumulation of data on a single group of people observed over a period of many years permits a variety of other types of analyses. Creative use of a longitudinal archive can amply justify the costs of maintaining the sample and should encourage investigators to initiate more longitudinal projects. Findings from the Baltimore Longitudinal Study of Aging are used to illustrate both traditional and alternative uses of personality data, including (a) development of nomological nets for the interpretation of personality measures, (b) evaluation of state effects in personality measurement, (c) validation of retrospective reports, and (d) heuristic exploratory analyses. Current knowledge on the stability of personality in adulthood, the correspondence of observer ratings and self-reports, and the comprehensiveness of the five-factor model can enhance the design of future longitudinal studies. RP COSTA, PT (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 78 TC 24 Z9 26 U1 1 U2 11 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD JUN PY 1992 VL 6 IS 2 BP 85 EP 102 DI 10.1002/per.2410060203 PG 18 WC Psychology, Social SC Psychology GA JA366 UT WOS:A1992JA36600002 ER PT J AU VICZIAN, A SANYAL, S TOFFENETTI, J CHADER, GJ FARBER, DB AF VICZIAN, A SANYAL, S TOFFENETTI, J CHADER, GJ FARBER, DB TI PHOTORECEPTOR-SPECIFIC MESSENGER-RNAS IN MICE CARRYING DIFFERENT ALLELIC COMBINATIONS AT THE RD AND RDS LOCI SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RD MOUSE; RDS MOUSE; RETINAL DEGENERATION; 48-KDA PROTEIN; OPSIN; ALPHA-SUBUNIT OF TRANSDUCIN; BETA-SUBUNIT OF CGMP-PHOSPHODIESTERASE ID DEGENERATION SLOW RDS; CYCLIC-GMP PHOSPHODIESTERASE; RETINAL DEGENERATION; MUTANT MICE; MOUSE RETINA; OUTER SEGMENTS; DISK MEMBRANE; GENE; LIGHT; EXPRESSION C1 UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. ERASMUS UNIV,DEPT ANAT,3000 DR ROTTERDAM,NETHERLANDS. NEI,BETHESDA,MD 20892. FU NEI NIH HHS [EY08285, EY02651, EY06841] NR 30 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 1992 VL 54 IS 6 BP 853 EP 860 DI 10.1016/0014-4835(92)90148-L PG 8 WC Ophthalmology SC Ophthalmology GA JF056 UT WOS:A1992JF05600004 PM 1381682 ER PT J AU SMITH, SB LEE, L NICKERSON, J SI, JS CHADER, GJ WIGGERT, B AF SMITH, SB LEE, L NICKERSON, J SI, JS CHADER, GJ WIGGERT, B TI SYNTHESIS AND SECRETION OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) AND DEVELOPMENTAL EXPRESSION OF IRBP MESSENGER-RNA IN NORMAL AND RD MOUSE RETINAS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN; MOUSE; RETINA; RETINAL DEGENERATION; RD MOUSE ID PHOTORECEPTOR CELLS; RHODOPSIN; DEGENERATION; SINGLE; MICE C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NEI NIH HHS [EY 06859] NR 25 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 1992 VL 54 IS 6 BP 957 EP 963 DI 10.1016/0014-4835(92)90160-T PG 7 WC Ophthalmology SC Ophthalmology GA JF056 UT WOS:A1992JF05600016 PM 1521586 ER PT J AU RUHL, S BEGLEY, CG BICKEL, M PLUZNIK, DH AF RUHL, S BEGLEY, CG BICKEL, M PLUZNIK, DH TI TRANSIENT EXPRESSION OF THE IL-2 RECEPTOR ALPHA-CHAIN IN IL-6-INDUCED MYELOID CELLS IS REGULATED BY AUTOCRINE PRODUCTION OF PROSTAGLANDIN-E2 SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 1991 ANNUAL MEETING OF THE INTERNATIONAL SOC FOR EXPERIMENTAL HEMATOLOGY CY JUL, 1991 CL PARMA, ITALY SP INT SOC EXPTL HEMATOL DE INTERLEUKIN-2 RECEPTOR; MYELOID DIFFERENTIATION; INTERLEUKIN-6; LEUKEMIA INHIBITORY FACTOR; PROSTAGLANDIN-E2 ID LEUKEMIA-INHIBITORY FACTOR; COLONY-STIMULATING FACTOR; INTERLEUKIN-2 RECEPTOR; GENE-EXPRESSION; SEQUENTIAL EXPRESSION; MOLECULAR-CLONING; BLOOD MONOCYTES; DIFFERENTIATION; MACROPHAGES; GROWTH AB The alpha-chain of the interleukin 2 receptor (IL-2R-alpha) is expressed on monocytes and macrophages after activation by bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). In the present study, we investigated whether the expression of IL-2R-alpha is associated with the process of differentation of myeloid cells to mature macrophages and how this expression is regulated. The murine myeloid M1 cell line, which can be induced by leukemia inhibitory factor (LIF) or interleukin 6 (IL-6) to differentiate from blast cells to mature macrophages, was used as a model system for myeloid differentiation. Bone marrow (BM)-derived macrophages were used as mature myeloid cells. Cytofluorometry revealed that IL-2R-alpha is transiently expressed during M1 cell differentiation, with peak levels 24 h after induction by LIF or IL-6, whereas the high affinity receptor for monomeric IgG2a (FcR), a surface marker typical for macrophage differentiation, continues to rise up to 72 h. BM-derived macrophages already expresses FcR but not Il-2R-alpha. IL-2R-alpha expression is induced on these cells after treatment by IL-6 for up to 48 h. Treatment of IL-6-induced M1 cells with indomethacin permitted a sustained expression of IL-2R-alpha beyond 24 h, and this effect was reversed by the addition of prostaglandin E2 (PGE2). Northern analysis showed that in M1 cells the expression of mRNA for IL-2R-alpha, but not for IL-2R-beta, is also transient, indicating that cell surface expression of IL-2R-alpha is regulated at the mRNA level. These data show that inducers of macrophage differentiation such as LIF and IL-6 can induce a transient expression of the IL-2R-alpha-chain in differentiating murine myeloid M1 cells and that autocrine production of PGE2 is involved in the control of the transient expression of this receptor. However, induction of expression of IL-2R-alpha by IL-6 appears to be independent of differentiation because it can be induced on fully differentiated BM-derived macrophages as well. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,HFB-800,BLDG 29A,ROOM 3B-19,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NIH,METAB BRANCH,BETHESDA,MD 20892. NR 40 TC 12 Z9 12 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 1992 VL 20 IS 5 BP 619 EP 625 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA HV569 UT WOS:A1992HV56900015 PM 1587308 ER PT J AU GYANG, FN PETERSON, DS WELLEMS, TE AF GYANG, FN PETERSON, DS WELLEMS, TE TI PLASMODIUM-FALCIPARUM - RAPID DETECTION OF DIHYDROFOLATE-REDUCTASE MUTATIONS THAT CONFER RESISTANCE TO CYCLOGUANIL AND PYRIMETHAMINE SO EXPERIMENTAL PARASITOLOGY LA English DT Note ID THYMIDYLATE SYNTHASE GENE; MOLECULAR-BASIS; MALARIA C1 UNIV GHANA,DEPT BIOCHEM,LEGON,GHANA. RP GYANG, FN (reprint author), NIAID,MALARIA RES LAB,BLDG 4 ROOM 126,BETHESDA,MD 20892, USA. NR 14 TC 33 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUN PY 1992 VL 74 IS 4 BP 470 EP 472 DI 10.1016/0014-4894(92)90209-S PG 3 WC Parasitology SC Parasitology GA HY296 UT WOS:A1992HY29600011 PM 1592095 ER PT J AU MELNICK, RL AF MELNICK, RL TI DOES CHEMICALLY-INDUCED HEPATOCYTE PROLIFERATION PREDICT LIVER CARCINOGENESIS SO FASEB JOURNAL LA English DT Review DE CELL PROLIFERATION; CELL LOSS; CHEMICAL CARCINOGENESIS; LIVER; S-PHASE HEPATOCYTES; ALTERED HEPATIC LOCI; NONGENOTOXIC CARCINOGENS; INITIATION; PROMOTION ID <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; INDUCED CELL-PROLIFERATION; UNSCHEDULED DNA-SYNTHESIS; CHOLINE-DEVOID DIET; MALE B6C3F1 MICE; RAT-LIVER; PEROXISOME PROLIFERATOR; INDUCED HYPERPLASIA; HEPATIC TUMORIGENESIS; CHRONIC TOXICITY AB Cell proliferation has long been recognized as having an important role in chemically induced carcinogenesis. Based on findings that certain nongenotoxic chemical carcinogens induced cell proliferation in the same organ that had an increased incidence of tumors, it has been hypothesized that a chemically induced response of enhanced DNA synthesis and cellular division causes cancer by increasing the rate of spontaneous mutations. It was further suggested that there would be no increased human risk of cancer by non-DNA-reactive compounds at doses that do not cause a proliferative response. An evaluation of the literature on the relationship between chemically induced cell proliferation and liver carcinogenesis reveals that very few systematic cell proliferation studies have been conducted over periods of extended exposure, and in many cases the exposure concentrations were not similar to those used in the cancer studies. The proliferative response resulting from exposure to many nongenotoxic carcinogens is not well sustained, whereas the carcinogenic response by these chemicals often requires prolonged exposure. The available literature leads to the conclusion that quantitative correspondences between cellular proliferation and carcinogenic responses have not been demonstrated and do not support the hypothesis that chemically induced cell proliferation is the primary mechanism by which nongenotoxic chemicals cause liver cancer. Studies of liver carcinogenesis in two-stage models point out the need to better understand chemical effects on cell loss as well as on cell replication, and demonstrate that measurements of cell proliferation alone are not sufficient to elucidate mechanisms of tumor development. RP MELNICK, RL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 63 TC 75 Z9 75 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 JUN PY 1992 VL 6 IS 9 BP 2698 EP 2706 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HZ481 UT WOS:A1992HZ48100011 PM 1612294 ER PT J AU FRANZOSO, G DIMITROV, DS BLUMENTHAL, R BARILE, MF ROTTEM, S AF FRANZOSO, G DIMITROV, DS BLUMENTHAL, R BARILE, MF ROTTEM, S TI FUSION OF MYCOPLASMA-FERMENTANS STRAIN INCOGNITUS WITH LYMPHOCYTES-T SO FEBS LETTERS LA English DT Article DE MYCOPLASMA-FERMENTANS; FUSION; LYMPHOCYTE; AIDS ID CELLS; INFECTIVITY; INHIBITION; BINDING AB The ability of Mycoplasma fermentans (strain incognitus) to fuse with cultured lymphocytes was investigated and the fusion process was characterized. Fusion was measured using an assay to determine lipid mixing based on the dequenching of the fluorescent probe, octadecylrhodamine (R18), that was incorporated into the mycoplasma cells. Fusion of M. fermentans was detected with both CD4+ (Molt 3) and CD4- (12-E1) cells. The amount of fusion induced was relatively low and ranged from 5-10% with either cell culture. When primary peripheral blood lymphocytes were used the fusion yield was somewhat higher, reaching 12% of the cell population. Similar findings were obtained with fluorescent microscopy analysis suggesting that a predetermined, but unidentified subpopulation of cultured lymphocytes. were being fused. The rate of fusion was temperature dependent. Following a short lag period fusion at 37-degrees-C was virtually completed in 60 min. The lymphocytes remained intact throughout the fusion process, as determined by the Trypan blue staining procedure. Fusion was almost completely inhibited by anti-M. fermentans antisera and by pretreatment of M. fermentans cells with proteolytic enzymes, suggesting that a surface-exposed proteinaceous component is involved in the fusion process. C1 US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20892. NCI,MATH BIOL LAB,MEMBRANE STRUCT & FUNCT LAB,BETHESDA,MD 20892. NR 14 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 1 PY 1992 VL 303 IS 2-3 BP 251 EP 254 DI 10.1016/0014-5793(92)80531-K PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA HZ693 UT WOS:A1992HZ69300033 PM 1607025 ER PT J AU BROOCKS, A AF BROOCKS, A TI ONDANSETRON - THE 1ST HIGHLY SELECTIVE 5-HT3 ANTAGONIST IN THE TREATMENT OF MENTAL DISEASES SO FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE LA German DT Article ID OBSESSIVE-COMPULSIVE DISORDER; 5-HYDROXYTRYPTAMINE UPTAKE BLOCKADE; CISPLATIN-INDUCED EMESIS; H-3 ICS 205-930; META-CHLOROPHENYLPIPERAZINE; SEROTONIN RECEPTORS; ALZHEIMERS-DISEASE; LABORATORY RATS; BEHAVIORAL-RESPONSES; RECOGNITION SITES AB Ondansetron is a highly selective 5-HT3 antagonist, which has recently become available for the control of chemotherapy-induced emesis. Since 5-HT3 receptors not only have a high density in the area postrema but also in the hippocampal and amygdala region of the limbic system, it has been suspected that 5-HT3 selective agents have psychotropic effects. In animal models of anxiety ondansetron showed a benzodiazepine-like anxiolytic effect without any sedation or withdrawal effects. Other states of withdrawal have been prevented with ondansetron. This agent might also exert neuroleptic effects since dopaminergic hyperactivity in the mesolimbic system was antagonised by ondansetron. In different models of memory and learning a positive effect on basal learning behaviour and on scopolamin-induced memory impairment was noted. This manuscript reviews essential pharmacological and behavioural effects of ondansetron as well as preliminary data from clinical studies. The role of highly-selective ligands for a more differentiated view of serotonergic subsystems are discussed. RP BROOCKS, A (reprint author), NIMH,CLIN SCI LAB,BLDG 10,3D41,BETHESDA,MD 20892, USA. NR 92 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0720-4299 J9 FORTSCHR NEUROL PSYC JI Forschritte Neurol. Psychiatr. PD JUN PY 1992 VL 60 IS 6 BP 227 EP 236 DI 10.1055/s-2007-999142 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JC994 UT WOS:A1992JC99400003 PM 1386589 ER PT J AU WELLER, M AF WELLER, M TI ANTI-PHOSPHOLIPID-ANTIBODIES AND CEREBRAL-ISCHEMIA SO FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE LA German DT Note ID ANTIPHOSPHOLIPID ANTIBODIES RP WELLER, M (reprint author), NIH,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 3N256,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0720-4299 J9 FORTSCHR NEUROL PSYC JI Forschritte Neurol. Psychiatr. PD JUN PY 1992 VL 60 IS 6 BP 246 EP 247 DI 10.1055/s-2007-999144 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JC994 UT WOS:A1992JC99400005 PM 1644403 ER PT J AU DIBISCEGLIE, AM AXIOTIS, CA HOOFNAGLE, JH BACON, BR AF DIBISCEGLIE, AM AXIOTIS, CA HOOFNAGLE, JH BACON, BR TI MEASUREMENTS OF IRON STATUS IN PATIENTS WITH CHRONIC HEPATITIS SO GASTROENTEROLOGY LA English DT Article ID CONTROLLED TRIAL; HEMOCHROMATOSIS; LIVER; INTERFERON; OVERLOAD; FERRITIN C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. LOUISIANA STATE UNIV,SCH MED,GASTROENTEROL & HEPATOL SECT,SHREVEPORT,LA 71105. RP DIBISCEGLIE, AM (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 4D 52,BETHESDA,MD 20892, USA. NR 21 TC 311 Z9 315 U1 1 U2 5 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 JUN PY 1992 VL 102 IS 6 BP 2108 EP 2113 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HW356 UT WOS:A1992HW35600037 PM 1587431 ER PT J AU LISKERMELMAN, M DIBISCEGLIE, AM USALA, SJ WEINTRAUB, B MURRAY, LM HOOFNAGLE, JH AF LISKERMELMAN, M DIBISCEGLIE, AM USALA, SJ WEINTRAUB, B MURRAY, LM HOOFNAGLE, JH TI DEVELOPMENT OF THYROID-DISEASE DURING THERAPY OF CHRONIC VIRAL-HEPATITIS WITH INTERFERON ALFA SO GASTROENTEROLOGY LA English DT Note ID CONTROLLED TRIAL; ALPHA-INTERFERON; AUTOIMMUNITY; EXPRESSION; HYPOTHYROIDISM; ANTIGEN C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 10,ROOM 4D 52,BETHESDA,MD 20892. NIDDKD,MOLEC CELLULAR & NUTR ENDOCRINOL,BETHESDA,MD 20892. NR 18 TC 213 Z9 215 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1992 VL 102 IS 6 BP 2155 EP 2160 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HW356 UT WOS:A1992HW35600046 PM 1587439 ER PT J AU SMITH, PD MAI, UEH AF SMITH, PD MAI, UEH TI IMMUNOPATHOPHYSIOLOGY OF GASTROINTESTINAL-DISEASE IN HIV-INFECTION SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; NECROSIS FACTOR-ALPHA; T-CELL SUBPOPULATION; LONG TERMINAL REPEAT; INTESTINAL M-CELLS; HOMOSEXUAL MEN; KAPOSIS-SARCOMA; SYNDROME AIDS; IMMUNOGLOBULIN PRODUCTION RP SMITH, PD (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30,ROOM 322,BETHESDA,MD 20892, USA. NR 100 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 1992 VL 21 IS 2 BP 331 EP 345 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HW327 UT WOS:A1992HW32700005 PM 1355076 ER PT J AU IRVING, JD OWEN, WJ LINSELL, J MCCULLAGH, M KEIGHTLEY, A ANGGIANSAH, A AF IRVING, JD OWEN, WJ LINSELL, J MCCULLAGH, M KEIGHTLEY, A ANGGIANSAH, A TI MANAGEMENT OF DIFFUSE ESOPHAGEAL SPASM WITH BALLOON DILATATION SO GASTROINTESTINAL RADIOLOGY LA English DT Article DE ESOPHAGUS, MOTILITY DISORDERS; DIFFUSE ESOPHAGEAL SPASM, DIAGNOSIS; ESOPHAGUS, BALLOON DILATATION ID PNEUMATIC DILATATION; CHEST PAIN AB Of 1200 patients referred to the esophageal laboratory at Guy's Hospital for investigation of suspected esophageal motility disorders, 61 (5.1%) were diagnosed as diffuse esophageal spasm. Twenty of these patients whose symptoms were severe did not respond to conservative treatment and were treated by balloon dilatation. Results were good in 14 and poor in six patients, which included one esophageal perforation. Diffuse esophageal spasm was diagnosed where more than 30% nonperistaltic activity was demonstrated by manometry. Lower esophageal sphincter pressure and relaxation were normal in all cases except one. Gastroesophageal reflux was present in four of five poor responders who were examined by 24-h ambulatory pH monitoring, and in only one of 10 good responders. Three of the six patients in whom balloon dilatation was successful proceeded to full-length myotomy, with relief of symptoms in two. The indications for, and results of, balloon dilatation in this condition are discussed, and a new radiological sign is described. C1 GUYS HOSP,DEPT RADIOL,LONDON SE1 9RT,ENGLAND. NIGMS,DEPT SURG,BETHESDA,MD 20892. NR 8 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2356 J9 GASTROINTEST RADIOL PD SUM PY 1992 VL 17 IS 3 BP 189 EP 192 DI 10.1007/BF01888544 PG 4 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA HQ609 UT WOS:A1992HQ60900001 PM 1612298 ER PT J AU THON, G KLAR, AJS AF THON, G KLAR, AJS TI THE CLR1 LOCUS REGULATES THE EXPRESSION OF THE CRYPTIC MATING-TYPE LOCI OF FISSION YEAST SO GENETICS LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; SEXUAL-DIFFERENTIATION; DNA STRANDS; GENES; TRANSPOSITION; CASSETTES; TRANSCRIPTION; MUTANTS; BREAKS AB The mat2-P and mat3-M loci of fission yeast contain respectively the plus (P) and minus (M) mating-type information in a transcriptionally silent state. That information is transposed from the mat2 or mat3 donor locus via recombination into the expressed mating-type locus (mat1) resulting in switching of the cellular mating type. We have identified a gene, named clr1 (for cryptic loci regulator), whose mutations allow expression of the mat2 and mat3 loci. clr1 mutants undergo aberrant haploid meiosis, indicative of transcription of the silent genes. Production of mRNA from mat3 is detectable in clr1 mutants. Furthermore, the ura4 gene inserted near mat3, weakly expressed in wild-type cells, is derepressed in clr1 mutants. The clr1 mutations also permit meiotic recombination in the 15-kb mat2-mat3 interval, where recombination is normally inhibited. The clr1 locus is in the right arm of chromosome II. We suggest that clr1 regulates silencing of the mat2 and mat3 loci, and participates in establishing the "cold spot" for recombination by organizing the chromatin structure of the mating-type region. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, EUKARYOT GENE EXPRESS LAB, FREDERICK, MD 21702 USA. RI Thon, Genevieve/L-9497-2014 OI Thon, Genevieve/0000-0001-8550-5945 FU NCI NIH HHS [N01-CO-74101] NR 46 TC 84 Z9 86 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD JUN PY 1992 VL 131 IS 2 BP 287 EP 296 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA HW759 UT WOS:A1992HW75900005 PM 1644273 ER PT J AU AVRAHAM, KB PREZIOSO, VR CHEN, WS LAI, E SLADEK, FM ZHONG, WM DARNELL, JE JENKINS, NA COPELAND, NG AF AVRAHAM, KB PREZIOSO, VR CHEN, WS LAI, E SLADEK, FM ZHONG, WM DARNELL, JE JENKINS, NA COPELAND, NG TI MURINE CHROMOSOMAL LOCATION OF 4 HEPATOCYTE-ENRICHED TRANSCRIPTION FACTORS - HNF-3-BETA, HNF-3-BETA, HNF-3-GAMMA, AND HNF-4 SO GENOMICS LA English DT Article ID MOUSE; LINKAGE; MAP C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,POB B,BLDG 539,FREDERICK,MD 21702. ROCKEFELLER UNIV,MOLEC CELL BIOL LAB,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021. FU NCI NIH HHS [N01-CO-74101] NR 21 TC 32 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1992 VL 13 IS 2 BP 264 EP 268 DI 10.1016/0888-7543(92)90241-J PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600004 PM 1612587 ER PT J AU TORY, K LATIF, F MODI, W SCHMIDT, L MING, HW HUA, L COBLER, P ORCUTT, ML DELISIO, J GEIL, L ZBAR, B LERMAN, MI AF TORY, K LATIF, F MODI, W SCHMIDT, L MING, HW HUA, L COBLER, P ORCUTT, ML DELISIO, J GEIL, L ZBAR, B LERMAN, MI TI A GENETIC-LINKAGE MAP OF 96-LOCI ON THE SHORT ARM OF HUMAN CHROMOSOME-3 SO GENOMICS LA English DT Article ID VONHIPPEL-LINDAU DISEASE; RENAL-CELL CARCINOMA; FRAGMENT LENGTH POLYMORPHISMS; LUNG-CANCER; LAMBDA-LIB28-56'' D3S207; INSITU HYBRIDIZATION; ALPHA-SATELLITE; MAPPING PANEL; DNA-SEQUENCE; HUMAN GENOME C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 74 TC 61 Z9 61 U1 1 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1992 VL 13 IS 2 BP 275 EP 286 DI 10.1016/0888-7543(92)90243-L PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600006 PM 1612588 ER PT J AU MANROW, RE LEONE, A KRUG, MS ESCHENFELDT, WH BERGER, SL AF MANROW, RE LEONE, A KRUG, MS ESCHENFELDT, WH BERGER, SL TI THE HUMAN PROTHYMOSIN-ALPHA GENE FAMILY CONTAINS SEVERAL PROCESSED PSEUDOGENES LACKING DELETERIOUS LESIONS SO GENOMICS LA English DT Article ID AUG INITIATOR CODON; MESSENGER-RNA; SEQUENCES; PROTEIN; CELLS; DNA; IDENTIFICATION; TRANSLATION; EXPRESSION; BINDING RP MANROW, RE (reprint author), NCI,BIOCHEM LAB,GENES & GENE PROD SECT,BETHESDA,MD 20892, USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 30 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1992 VL 13 IS 2 BP 319 EP 331 DI 10.1016/0888-7543(92)90248-Q PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600011 PM 1612591 ER PT J AU KELLEY, KA STAMM, S KOZAK, CA AF KELLEY, KA STAMM, S KOZAK, CA TI EXPRESSION AND CHROMOSOME LOCALIZATION OF THE MURINE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR SO GENOMICS LA English DT Article ID POLYMERASE CHAIN-REACTION; RIBONUCLEIC-ACID; DNA; GENE; IDENTIFICATION; MUTATIONS; RNA; CLUSTER; PROBES; LOCUS C1 NIAID,BETHESDA,MD 20892. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. RP KELLEY, KA (reprint author), CUNY MT SINAI SCH MED,ARTHUR M FISHBERG RES CTR NEUROBIOL,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. FU NIDDK NIH HHS [DK-43973] NR 28 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1992 VL 13 IS 2 BP 381 EP 388 DI 10.1016/0888-7543(92)90257-S PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600020 PM 1377165 ER PT J AU LOCK, LF PINES, J HUNTER, T GILBERT, DJ GOPALAN, G JENKINS, NA COPELAND, NG DONOVAN, PJ AF LOCK, LF PINES, J HUNTER, T GILBERT, DJ GOPALAN, G JENKINS, NA COPELAND, NG DONOVAN, PJ TI A SINGLE CYCLIN-A GENE AND MULTIPLE CYCLIN-B1-RELATED SEQUENCES ARE DISPERSED IN THE MOUSE GENOME SO GENOMICS LA English DT Article ID ALBINO-DELETION COMPLEX; BACKCROSS LINKAGE MAP; INTERSPECIFIC BACKCROSS; MESSENGER-RNA; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL LOCATION; PROTEIN-KINASE; T/T COMPLEX; M-PHASE C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. SALK INST BIOL STUDIES,MOLEC BIOL & VIROL LAB,SAN DIEGO,CA 92186. OI Pines, Jonathon/0000-0002-5227-6004 FU PHS HHS [N01-C0-74101] NR 78 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1992 VL 13 IS 2 BP 415 EP 424 DI 10.1016/0888-7543(92)90262-Q PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600025 PM 1535334 ER PT J AU CEBRATHOMAS, JA TSAI, JY PILDER, SH COPELAND, NG JENKINS, NA SILVER, LM AF CEBRATHOMAS, JA TSAI, JY PILDER, SH COPELAND, NG JENKINS, NA SILVER, LM TI LOCALIZATION OF THE MAS PROTOONCOGENE TO A DENSELY MARKED REGION OF MOUSE CHROMOSOME-17 ASSOCIATED WITH GENOMIC IMPRINTING SO GENOMICS LA English DT Note ID T-HAPLOTYPES; RAT-BRAIN; COMPLEX C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP CEBRATHOMAS, JA (reprint author), PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544, USA. FU PHS HHS [N01-C0-74101] NR 19 TC 15 Z9 15 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 JUN PY 1992 VL 13 IS 2 BP 444 EP 446 DI 10.1016/0888-7543(92)90267-V PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600030 PM 1612602 ER PT J AU TRAUPE, H VANDENOUWELAND, AMW VANOOST, BA VOGEL, W VETTER, U WARREN, ST ROCCHI, M DARLISON, MG ROPERS, HH AF TRAUPE, H VANDENOUWELAND, AMW VANOOST, BA VOGEL, W VETTER, U WARREN, ST ROCCHI, M DARLISON, MG ROPERS, HH TI FINE MAPPING OF THE HUMAN BIGLYCAN (BGN) GENE WITH THE XQ28 REGION EMPLOYING A HYBRID CELL PANEL SO GENOMICS LA English DT Note ID DOMINANT CHONDRODYSPLASIA PUNCTATA; GROWTH-FACTOR-BETA; DECORIN; PROTEOGLYCANS; LOCALIZATION; EXPRESSION; LINKAGE; LOCUS C1 UNIV ULM, DEPT CLIN GENET, W-7900 ULM, GERMANY. MRC, MOLEC NEUROBIOL UNIT, CAMBRIDGE CB2 2QH, ENGLAND. EMORY UNIV, SCH MED, DEPT PEDIAT, ATLANTA, GA 30322 USA. UNIV BARI, INST GENET, I-70126 BARI, ITALY. EMORY UNIV, SCH MED, DEPT BIOCHEM, ATLANTA, GA 30322 USA. EMORY UNIV, SCH MED, HOWARD HUGHES MED INST, ATLANTA, GA 30322 USA. NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. RP TRAUPE, H (reprint author), UNIV HOSP NIJMEGEN, DEPT HUMAN GENET, POB 9101, 6500 HB NIJMEGEN, NETHERLANDS. RI Warren, Stephen/A-2498-2012 NR 19 TC 37 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1992 VL 13 IS 2 BP 481 EP 483 DI 10.1016/0888-7543(92)90279-2 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HT926 UT WOS:A1992HT92600042 PM 1612609 ER PT J AU BUTLER, RN FINKEL, SI LEWIS, MI SHERMAN, FT SUNDERLAND, T AF BUTLER, RN FINKEL, SI LEWIS, MI SHERMAN, FT SUNDERLAND, T TI AGING AND MENTAL-HEALTH - DIAGNOSIS OF DEMENTIA AND DEPRESSION - A ROUND-TABLE DISCUSSION .2. SO GERIATRICS LA English DT Article AB In this second segment of a panel discussion on aging and mental health, panelists focus on the primary care evaluation and management of the patient with dementia, including differential diagnosis of depression. Other topics of discussion include the roles of psychiatric referral and psychotherapy in patient management suicide prevention, and alcoholism in elderly patients. C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NW MEM HOSP,GEROPSYCHIATR SERV,CHICAGO,IL 60611. CUNY MT SINAI SCH MED,DEPT COMMUNITY MED,DIV SOCIAL WORK,NEW YORK,NY 10029. NIMH,CHEVY CHASE,MD. RP BUTLER, RN (reprint author), CUNY MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD JUN PY 1992 VL 47 IS 6 BP 49 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA HX664 UT WOS:A1992HX66400004 PM 1592268 ER PT J AU GAGE, DA RATHKE, E COSTELLO, CE JONES, MZ AF GAGE, DA RATHKE, E COSTELLO, CE JONES, MZ TI DETERMINATION OF SEQUENCE AND LINKAGE OF TISSUE OLIGOSACCHARIDES IN CAPRINE BETA-MANNOSIDOSIS BY FAST-ATOM-BOMBARDMENT, COLLISIONALLY ACTIVATED DISSOCIATION TANDEM MASS-SPECTROMETRY SO GLYCOCONJUGATE JOURNAL LA English DT Article DE BETA-MANNOSIDOSIS OLIGOSACCHARIDES; SEQUENCE AND LINKAGE DETERMINATION; ABEE DERIVATIVES ID STRUCTURAL-ANALYSIS; KIDNEY; IONS AB Fast atom bombardment, collisionally activated dissociation tandem mass spectrometry (FAB-CAD-MS/MS), combined with p-aminobenzoic acid ethyl ester (ABEE) derivatization, were used to confirm the sequence and linkage pattern of subnanomolar amounts of the previously characterized three major thyroid gland oligosaccharides accumulated in caprine beta-mannosidosis. Positive ion FAB-CAD-MS/MS of both the [M + H]+ and [M + Na]+ ions from the ABEE derivatized oligosaccharides produced product ions derived from cleavage of the glycosidic bonds which allowed the sequences to be determined. Several fragments resulting from cleavages across the sugar ring permitted the assignment, in some cases, of the linkage positions between the sugar residues. The natriated molecule yielded several fragments of this type which were not observed when the protonated molecule was selected as the precursor ion. Use of these techniques gave the complete sequence and linkage characterization of the disaccharide and complete sequence and partial linkage information for the two higher oligosaccharides. C1 MIT,DEPT CHEM,NIH,MASS SPECT FACIL,CAMBRIDGE,MA 02139. MICHIGAN STATE UNIV,DEPT PATHOL,E LANSING,MI 48824. RP GAGE, DA (reprint author), MICHIGAN STATE UNIV,DEPT BIOCHEM,NIH,MASS SPECT FACIL,E LANSING,MI 48824, USA. FU NCRR NIH HHS [RR-00317, RR-00480]; NINDS NIH HHS [NS-16886] NR 19 TC 9 Z9 9 U1 1 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD JUN PY 1992 VL 9 IS 3 BP 126 EP 131 DI 10.1007/BF00780759 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JD845 UT WOS:A1992JD84500004 PM 1422131 ER PT J AU RECHLER, MM BROWN, AL AF RECHLER, MM BROWN, AL TI INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS - GENE STRUCTURE AND EXPRESSION SO GROWTH REGULATION LA English DT Review DE IGF; IGF BINDING PROTEIN; TRANSCRIPTION; PROMOTER; LIVER FACTOR-B1; INSULIN RESPONSE ELEMENT ID FOLLICLE-STIMULATING-HORMONE; HUMAN CHROMOSOMAL GENE; BREAST-CANCER-CELLS; FACTOR IGF BINDING; MESSENGER-RNA; TISSUE DISTRIBUTION; FETAL-RAT; CEREBROSPINAL-FLUID; COMPLEMENTARY-DNA; PROMOTER ACTIVITY RP RECHLER, MM (reprint author), NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, GROWTH & DEV SECT, BLDG 10, ROOM 8D14, BETHESDA, MD 20892 USA. NR 100 TC 140 Z9 140 U1 3 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD JUN PY 1992 VL 2 IS 2 BP 55 EP 68 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JA002 UT WOS:A1992JA00200001 PM 1283099 ER PT J AU SUZUKI, H LEE, YC TACHIBANA, M HOZAWA, K WATAYA, H TAKASAKA, T AF SUZUKI, H LEE, YC TACHIBANA, M HOZAWA, K WATAYA, H TAKASAKA, T TI QUANTITATIVE CARBOHYDRATE ANALYSES OF THE TECTORIAL AND OTOCONIAL MEMBRANES OF THE GUINEA-PIG SO HEARING RESEARCH LA English DT Article DE TECTORIAL MEMBRANE; OTOCONIAL MEMBRANE; CARBOHYDRATE COMPOSITION; HIGH-PERFORMANCE ANION-EXCHANGE CHROMATOGRAPHY; GLYCOPEPTIDASE-F; ENDO-BETA-GALACTOSIDASE ID ANION-EXCHANGE CHROMATOGRAPHY; LOCALIZATION; COLLAGEN; LECTINS; PROTEIN AB Carbohydrate composition of the tectorial membrane (TM) and the otoconial membrane (OM) of the guinea pig was analyzed after hydrolysis, using high-performance anion-exchange chromatography and pulsed amperometric detection. Both of the tissues were highly glycosylated; the carbohydrate content being 24-42% of protein. GlcN, Gal, Glc and Man were found to be the major component sugars of TM, whereas little GalN was found. Fuc and NANA were also present, but NGNA was not detectable. After digestion with thermolysin for solubilization, OM was separated into two fractions: insoluble mineral particles of the otoconia (OM-ppt) and a soluble fraction from the gelatinous layer (OM-sup). These two fractions showed distinct carbohydrate composition from each other. Further analyses using glycosidases revealed that TM contained asialyl and monosialyl but little di-, tri- and tetrasialyl N-glycosides, and OM-sup did not seem to be susceptible to endo-beta-galactosidase, which is known to cleave some N-acetyl-polylactosamine and keratan sulfate. Based on these analyses, it can be suggested that most of the carbohydrates in TM are likely to be asialyl and monosialyl N-glycosides. N-Glycosides may be predominant in the otoconia as well, and a polymer structure consisting of GlcN(Ac) and Gal other than N-acetyl-poly-lactosamine may exist in the gelatinous layer of OM. O-Glycosylation of the usual type appeared to be minor in all the fractions. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NIDOCD,MOLEC BIOL LAB,BETHESDA,MD. RP SUZUKI, H (reprint author), TOHOKU UNIV,SCH MED,DEPT OTOLARYNGOL,1-1 SEIRYO CHO,SENDAI,MIYAGI 980,JAPAN. NR 40 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 1992 VL 60 IS 1 BP 45 EP 52 DI 10.1016/0378-5955(92)90057-T PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA JB648 UT WOS:A1992JB64800006 PM 1500376 ER PT J AU SHINDO, M DIBISCEGLIE, AM HOOFNAGLE, JH AF SHINDO, M DIBISCEGLIE, AM HOOFNAGLE, JH TI LONG-TERM FOLLOW-UP OF PATIENTS WITH CHRONIC HEPATITIS-C TREATED WITH ALPHA-INTERFERON SO HEPATOLOGY LA English DT Article ID NON-B-HEPATITIS; NON-A-HEPATITIS; CONTROLLED TRIAL; VIRUS; GENOME; ALFA AB We reanalyzed the results of a pilot study of recombinant alpha-interferon therapy for chronic non-A, non-B hepatitis in light of the recent discovery of the hepatitis C virus and the development of diagnostic assays for this agent. Stored serum samples from 10 patients treated between 1984 and 1986 were tested for antibody to hepatitis C virus and hepatitis C virus RNA before, during and after therapy. In addition, the current clinical, serum biochemical and virological statuses of these patients were evaluated to determine the long-term effects of interferon therapy. All patients had evidence of hepatitis C virus infection, with hepatitis C viral RNA, antibody to hepatitis C virus or both markers detectable in serum. Serum hepatitis C virus RNA was found to disappear in seven of eight patients whose aminotransferase levels became normal with interferon therapy but remained present in two patients who did not respond to therapy. Levels of hepatitis C virus RNA decreased and disappeared when serum aminotransferases fell to normal levels but rose with subsequent elevation of aminotransferase levels in two patients who had relapses in disease when interferon was stopped. During a follow-up of 3 to 6 yr, hepatitis C virus RNA remained undetectable in the six patients whose serum aminotransferase levels remained normal after interferon therapy. However, neither initial titers of hepatitis C virus RNA nor disappearance of viral RNA from serum during treatment predicted a sustained response. Thus long-term beneficial responses to alpha-interferon can occur in patients with chronic hepatitis C and are associated with sustained loss of hepatitis C virus RNA from serum. RP SHINDO, M (reprint author), NIDDK,LIVER DIS SECT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 15 TC 222 Z9 222 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1992 VL 15 IS 6 BP 1013 EP 1016 DI 10.1002/hep.1840150607 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HX532 UT WOS:A1992HX53200006 PM 1317338 ER PT J AU ANDERSON, WF AF ANDERSON, WF TI MUSINGS ON THE STRUGGLE .1. THE PHONEBOOK SO HUMAN GENE THERAPY LA English DT Editorial Material ID MEDIATED GENE-TRANSFER; ADENOSINE-DEAMINASE RP ANDERSON, WF (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,7D-18,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN PY 1992 VL 3 IS 3 BP 251 EP 252 DI 10.1089/hum.1992.3.3-251 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA HZ454 UT WOS:A1992HZ45400001 PM 1643146 ER PT J AU CORNETTA, K TRICOT, G BROUN, ER HROMAS, R SROUR, E HOFFMAN, R ANDERSON, WF MOEN, RC MORGAN, RA AF CORNETTA, K TRICOT, G BROUN, ER HROMAS, R SROUR, E HOFFMAN, R ANDERSON, WF MOEN, RC MORGAN, RA TI RETROVIRAL-MEDIATED GENE-TRANSFER OF BONE-MARROW CELLS DURING AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIA SO HUMAN GENE THERAPY LA English DT Editorial Material ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN ADENOSINE-DEAMINASE; ACUTE NONLYMPHOBLASTIC LEUKEMIA; TUMOR INFILTRATING LYMPHOCYTES; ACUTE MYELOGENOUS LEUKEMIA; 1ST COMPLETE REMISSION; ACUTE MYELOID-LEUKEMIA; MONOCLONAL-ANTIBODIES; METASTATIC MELANOMA C1 GENET THERAPY INC,GAITHERSBURG,MD 20878. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. RP CORNETTA, K (reprint author), DEPT MED,HEMATOL ONCOL SECT,MED RES & LIB BLDG,975 W WALNUT ST,INDIANAPOLIS,IN 46202, USA. NR 54 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN PY 1992 VL 3 IS 3 BP 305 EP 318 DI 10.1089/hum.1992.3.3-305 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA HZ454 UT WOS:A1992HZ45400008 PM 1643150 ER PT J AU HOEHE, MR PLAETKE, R OTTERUD, B STAUFFER, D HOLIK, J BYERLEY, WF BAETGE, EE GERSHON, ES LALOUEL, JM LEPPERT, M AF HOEHE, MR PLAETKE, R OTTERUD, B STAUFFER, D HOLIK, J BYERLEY, WF BAETGE, EE GERSHON, ES LALOUEL, JM LEPPERT, M TI GENETIC-LINKAGE OF THE HUMAN GENE FOR PHENYLETHANOL-AMINE N-METHYLTRANSFERASE (PNMT), THE ADRENALINE-SYNTHESIZING ENZYME, TO DNA MARKERS ON CHROMOSOME-17Q21-Q22 SO HUMAN MOLECULAR GENETICS LA English DT Article ID STRAIN-SPECIFIC DIFFERENCES; BRAIN-STEM; HYPERTENSIVE RATS; BLOOD-PRESSURE; METHYL TRANSFERASE; RECEPTOR NUMBER; HPNMT GENE; EPINEPHRINE; NEURONS; POLYMORPHISM AB We have determined the genetic location of the human gene encoding phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine pathway catalyzing the synthesis of epinephrine (adrenaline) from norepinephrine. This gene is linked to DNA markers on the long arm of chromosome 17, q21-q22, most closely to the DNA markers MFD15 (D17S250) (Z(max) = 15.0, theta = 0.065) and fLB17.1 (Z(max) = 14.6, theta = 0.045). Multipoint linkage analysis placed the PNMT locus in the interval fLB17.1-CMM86 (D17S74), at 4 centiMorgans (cM) distal to fLB17.1, and at 17 cM proximal to CMM86. Mapping of the PNMT gene will provide the basis for genetic linkage studies in families with diseases which might pathogenetically involve this enzyme. The human chromosomal region 17q21-22 identified here to harbour the PNMT gene may be syntenic to the chromosomal region in the stroke-prone spontaneously hypertensive rat (SHR-SP) recently linked to blood-pressure regulation. As an increase of PNMT activity has been associated with the development of hypertension in SHR-SP, it will be of interest to perform comparative mapping of the PNMT gene. C1 NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. UNIV UTAH, SCH MED, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84132 USA. UNIV UTAH, SCH MED, DEPT HUMAN GENET, SALT LAKE CITY, UT 84132 USA. UNIV UTAH, SCH MED, DEPT PSYCHIAT, SALT LAKE CITY, UT 84132 USA. BRISTOL MEYERS SQUIBB, WALLINGFORD, CT 06492 USA. NR 38 TC 17 Z9 17 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1992 VL 1 IS 3 BP 175 EP 178 DI 10.1093/hmg/1.3.175 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JN242 UT WOS:A1992JN24200007 PM 1303174 ER PT J AU BHATIA, K GUTIERREZ, MI MAGRATH, IT AF BHATIA, K GUTIERREZ, MI MAGRATH, IT TI A NOVEL MUTATION IN THE P53 GENE IN A BURKITTS-LYMPHOMA CELL-LINE SO HUMAN MOLECULAR GENETICS LA English DT Article ID LUNG-CANCER; MUTANT P53; ONCOGENE; TRANSFORMATION; FREQUENT C1 NCI, PEDIAT BRANCH, LYMPHOMA BIOL SECT, BETHESDA, MD 20892 USA. NR 17 TC 5 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1992 VL 1 IS 3 BP 207 EP 208 DI 10.1093/hmg/1.3.207 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JN242 UT WOS:A1992JN24200015 PM 1303181 ER PT J AU WILCOX, ER RIVOLTA, MN PLOPLIS, B POTTERF, SB FEX, J AF WILCOX, ER RIVOLTA, MN PLOPLIS, B POTTERF, SB FEX, J TI THE PAX3 GENE IS MAPPED TO HUMAN CHROMOSOME-2 TOGETHER WITH A HIGHLY INFORMATIVE CA DINUCLEOTIDE REPEAT SO HUMAN MOLECULAR GENETICS LA English DT Article C1 NIDCD, MOLEC BIOL LAB, BETHESDA, MD USA. NR 5 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1992 VL 1 IS 3 BP 215 EP 215 DI 10.1093/hmg/1.3.215-a PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JN242 UT WOS:A1992JN24200021 PM 1303187 ER PT J AU MOSKALUK, CA MERINO, MJ DANFORTH, DN MEDEIROS, LJ AF MOSKALUK, CA MERINO, MJ DANFORTH, DN MEDEIROS, LJ TI LOW-GRADE ANGIOSARCOMA OF THE SKIN OF THE BREAST - A COMPLICATION OF LUMPECTOMY AND RADIATION-THERAPY FOR BREAST-CARCINOMA SO HUMAN PATHOLOGY LA English DT Article DE ANGIOSARCOMA; RADIATION THERAPY; BREAST CARCINOMA ID CUTANEOUS ANGIOSARCOMA; CHEST WALL C1 NCI,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 13 TC 55 Z9 56 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 1992 VL 23 IS 6 BP 710 EP 714 DI 10.1016/0046-8177(92)90331-V PG 5 WC Pathology SC Pathology GA HX651 UT WOS:A1992HX65100021 PM 1317346 ER PT J AU BHAT, NK PAPAS, TS AF BHAT, NK PAPAS, TS TI CHARACTERIZATION AND USES OF MONOCLONAL-ANTIBODY DERIVED AGAINST DNA-BINDING DOMAIN OF THE ETS FAMILY OF GENES SO HYBRIDOMA LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; LONG TERMINAL REPEAT; C-ETS; PROTO-ONCOGENE; TRANSCRIPTIONAL ACTIVATION; C-ETS-1 PROTOONCOGENE; ACTIVITY INVITRO; LEUKEMIA-VIRUS; IDENTIFICATION; PROTEINS AB A monoclonal antibody recognizing ets proteins from a variety of species has been developed. This antibody recognizes ets1, ets2, erg, and other related proteins. It has a high affinity for the etsl protein. The epitope for the pan ets mAb consists of about 13 amino acids. This antibody can be used to isolate and characterize new members of ets gene family derived from a c-DNA expression library, as well as to identify other "ets motif" binding proteins. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP BHAT, NK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,POB B,BLDG 469,ROOM 221,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 58 TC 17 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1992 VL 11 IS 3 BP 277 EP 294 DI 10.1089/hyb.1992.11.277 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA JK419 UT WOS:A1992JK41900002 PM 1500064 ER PT J AU RUTAN, GH HERMANSON, B BILD, DE KITTNER, SJ LABAW, F TELL, GS AF RUTAN, GH HERMANSON, B BILD, DE KITTNER, SJ LABAW, F TELL, GS TI ORTHOSTATIC HYPOTENSION IN OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY SO HYPERTENSION LA English DT Article DE ORTHOSTATIC HYPOTENSION; CARDIOVASCULAR DISEASE; CEREBROVASCULAR DISEASE; AGING; SYSTOLIC HYPERTENSION ID BLOOD-PRESSURE; POSTURAL CHANGES; COGNITIVE PERFORMANCE; HYPERTENSION; DEMENTIA; DISEASE; RISK AB The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology. C1 CHS COORDINATING CTR,1107 NE 45TH,ROOM 530,SEATTLE,WA 98105. UNIV TENNESSEE CTR HLTH SCI,DEPT VET AFFAIRS,MEMPHIS,TN 38163. UNIV TENNESSEE CTR HLTH SCI,DEPT MED,MEMPHIS,TN 38163. UNIV TENNESSEE CTR HLTH SCI,DEPT PREVENT MED,MEMPHIS,TN 38163. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT EPIDEMIOL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PREVENT MED,BALTIMORE,MD 21201. UNIV CALIF DAVIS,SACRAMENTO MED CTR,DEPT COMMUNITY HLTH,SACRAMENTO,CA 95817. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086] NR 37 TC 319 Z9 328 U1 5 U2 17 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1992 VL 19 IS 6 BP 508 EP 519 PN 1 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HX022 UT WOS:A1992HX02200002 PM 1592445 ER PT J AU ENSOLI, B BARILLARI, G GALLO, RC AF ENSOLI, B BARILLARI, G GALLO, RC TI CYTOKINES AND GROWTH-FACTORS IN THE PATHOGENESIS OF AIDS-ASSOCIATED KAPOSIS-SARCOMA SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ACQUIRED IMMUNODEFICIENCY SYNDROME; TUMOR NECROSIS FACTOR; IMMUNE-DEFICIENCY SYNDROME; YOUNG HOMOSEXUAL MEN; CELLS; EXPRESSION; HIV-1; PDGF; INTERLEUKIN-1; AUTOCRINE C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 49 TC 129 Z9 130 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1992 VL 127 BP 147 EP 155 DI 10.1111/j.1600-065X.1992.tb01412.x PG 9 WC Immunology SC Immunology GA JD818 UT WOS:A1992JD81800007 PM 1506004 ER PT J AU SHER, A GAZZINELLI, RT OSWALD, IP CLERICI, M KULLBERG, M PEARCE, EJ BERZOFSKY, JA MOSMANN, TR JAMES, SL MORSE, HC SHEARER, GM AF SHER, A GAZZINELLI, RT OSWALD, IP CLERICI, M KULLBERG, M PEARCE, EJ BERZOFSKY, JA MOSMANN, TR JAMES, SL MORSE, HC SHEARER, GM TI ROLE OF T-CELL DERIVED CYTOKINES IN THE DOWN-REGULATION OF IMMUNE-RESPONSES IN PARASITIC AND RETROVIRAL INFECTION SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ACQUIRED IMMUNODEFICIENCY SYNDROME; INTERFERON-GAMMA; MACROPHAGE ACTIVATION; MURINE LEISHMANIASIS; TOXOPLASMA-GONDII; NITROGEN-OXIDES; C57BL/6 MICE; IMMUNOREGULATION; ABNORMALITIES; SUBSETS C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT MICROBIOL IMMUNOL & PARASITOL,ITHACA,NY 14853. UNIV ALBERTA,DEPT IMMUNOL,EDMONTON T6G 2E1,ALBERTA,CANADA. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RP SHER, A (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI OSWALD, Isabelle/A-8497-2013; OI Morse, Herbert/0000-0002-9331-3705; OSWALD, Isabelle/0000-0001-9918-277X NR 64 TC 438 Z9 445 U1 0 U2 10 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1992 VL 127 BP 183 EP 204 DI 10.1111/j.1600-065X.1992.tb01414.x PG 22 WC Immunology SC Immunology GA JD818 UT WOS:A1992JD81800009 PM 1354651 ER PT J AU URBAN, JF MADDEN, KB SVETIC, A CHEEVER, A TROTTA, PP GAUSE, WC KATONA, IM FINKELMAN, FD AF URBAN, JF MADDEN, KB SVETIC, A CHEEVER, A TROTTA, PP GAUSE, WC KATONA, IM FINKELMAN, FD TI THE IMPORTANCE OF TH2-CYTOKINES IN PROTECTIVE IMMUNITY TO NEMATODES SO IMMUNOLOGICAL REVIEWS LA English DT Review ID STIMULATORY FACTOR-I; T-CELL SUBSETS; INTERFERON-GAMMA; LYMPHOCYTES-T; B-CELLS; NIPPOSTRONGYLUS-BRASILIENSIS; MURINE LEISHMANIASIS; MONOCLONAL-ANTIBODY; INFECTED-RATS; IGE RESPONSE C1 USDA ARS,BELTSVILLE AGR RES CTR,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BELTSVILLE,MD 20705. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PEDIAT,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT MICROBIOL,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT MED,BETHESDA,MD 20814. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. SCHERING RES INST,SCHERING RES,DIV BIOTECHNOL BIOCHEM,BLOOMFIELD,NJ 07003. OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [AI-21328, AI-26150] NR 70 TC 315 Z9 320 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1992 VL 127 BP 205 EP 220 DI 10.1111/j.1600-065X.1992.tb01415.x PG 16 WC Immunology SC Immunology GA JD818 UT WOS:A1992JD81800010 PM 1354652 ER PT J AU BENHAMOU, M SIRAGANIAN, RP AF BENHAMOU, M SIRAGANIAN, RP TI PROTEIN-TYROSINE PHOSPHORYLATION - AN ESSENTIAL COMPONENT OF FC-EPSILON-RI SIGNALING SO IMMUNOLOGY TODAY LA English DT Article ID HISTAMINE-RELEASE AB Mast cell and basophil activation can be achieved by antigen-mediated aggregation of cell surface Fc-epsilon-RI molecules. At least two signaling pathways are triggered by this activation. Both involve tyrosine phosphorylation. This aspect of Fc-epsilon-RI signaling is examined here in detail and its position in a complex network of post-binding events assessed. RP BENHAMOU, M (reprint author), NIDR,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 15 TC 153 Z9 153 U1 0 U2 1 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 JUN PY 1992 VL 13 IS 6 BP 195 EP 197 DI 10.1016/0167-5699(92)90152-W PG 3 WC Immunology SC Immunology GA HW968 UT WOS:A1992HW96800001 PM 1320890 ER PT J AU EIDEN, LE LIFSON, JD AF EIDEN, LE LIFSON, JD TI HIV INTERACTIONS WITH CD4 - A CONTINUUM OF CONFORMATIONS AND CONSEQUENCES SO IMMUNOLOGY TODAY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III/LAV ENVELOPE; BINDING-SITE; SYNCYTIUM FORMATION; AIDS RETROVIRUS; SOLUBLE CD4; GLYCOPROTEIN; INFECTION; GP120; RECEPTOR AB Here, Lee Eiden and Jeffrey Lifson present a model for HIV envelope glycoprotein-CD4 interactions that attempts to reconcile recent, seemingly conflicting, structural, biochemical and biological observations. Central to this model is the involvement of both the CDR2-like and CDR3-like domains of CD4 in the interaction with gp120, leading to a conformational change and dissociation of gp120 from the gp120-gp41 complex. C1 GENELABS INC,DIV HUMAN IMMUNODEFICIENCY VIRUS & EXPLORAT RES,REDWOOD CITY,CA 94063. RP EIDEN, LE (reprint author), NIMH,CELL BIOL LAB,MOLEC & CELLULAR BIOL UNIT,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X FU NIAID NIH HHS [AI25922] NR 52 TC 59 Z9 59 U1 0 U2 3 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 JUN PY 1992 VL 13 IS 6 BP 201 EP 206 DI 10.1016/0167-5699(92)90154-Y PG 6 WC Immunology SC Immunology GA HW968 UT WOS:A1992HW96800004 PM 1627247 ER PT J AU HARRISON, ET LUYTEN, FP REDDI, AH AF HARRISON, ET LUYTEN, FP REDDI, AH TI TRANSFORMING GROWTH-FACTOR-BETA - ITS EFFECT ON PHENOTYPE REEXPRESSION BY DEDIFFERENTIATED CHONDROCYTES IN THE PRESENCE AND ABSENCE OF OSTEOGENIN SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE TGF-BETA; OSTEOGENIN; CHONDROCYTE PHENOTYPE REEXPRESSION ID EXTRACELLULAR-MATRIX; COLLAGEN; BONE; DIFFERENTIATION; STIMULATION; EXPRESSION; PROTEOGLYCANS; PURIFICATION; FIBRONECTIN; FIBROBLASTS AB The single and combined actions of transforming growth factor (TGF)-beta and osteogenin were evaluated with regard to induction of colony formation and reexpression of the differentiated phenotype by dedifferentiated rabbit articular chondrocytes in soft agarose under serum-free conditions. TGF-beta alone did not promote colony formation and induced accumulation of proteoglycans and type II collagen at significantly lower levels than those induced by osteogenin. Although synergism between these two growth factors occurred with respect to the induction of colony formation, their joint action on reexpression of the differentiated phenotype was additive. Complex interactions between the two growth factors may explain the latter phenomenon. RP HARRISON, ET (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BONE CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 24 TC 16 Z9 16 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DR,STE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUN PY 1992 VL 28A IS 6 BP 445 EP 448 PG 4 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA JE072 UT WOS:A1992JE07200014 ER PT J AU YUAN, Y LYNG, K ZHANG, YX ROCKEY, DD MORRISON, RP AF YUAN, Y LYNG, K ZHANG, YX ROCKEY, DD MORRISON, RP TI MONOCLONAL-ANTIBODIES DEFINE GENUS-SPECIFIC, SPECIES-SPECIFIC, AND CROSS-REACTIVE EPITOPES OF THE CHLAMYDIAL 60-KILODALTON HEAT-SHOCK PROTEIN (HSP60) - SPECIFIC IMMUNODETECTION AND PURIFICATION OF CHLAMYDIAL HSP60 SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI; ULTRASTRUCTURAL ANALYSIS; DISEASE PATHOGENESIS; INTERFERON-GAMMA; TRACHOMATIS; ANTIGEN; BACTERIAL; PSITTACI; GROWTH AB Ocular and urogenital tract infections with Chlamydia trachomatis can progress to chronic inflammatory diseases that produce blindness and tubal infertility. The pathophysiology of these chronic disease conditions is thought to be immunologically mediated, and the chlamydial 60-kDa heat shock protein (hsp60) has been implicated as a major target antigen that stimulates the immunopathological response. The lack of chlamydial hsp60 antibodies and purified hsp60 has severely restricted studies to define more thoroughly the role of this protein in the immunopathogenesis of chlamydial disease. We produced a panel of antichlamydial hsp60 monoclonal antibodies (MAbs) and defined their specificities by immunoblotting against lysates of C. trachomatis, C. psittaci, and six other genera of bacteria. Three patterns of anti-hsp60 immunoreactivity were observed: chlamydial species specific, chlamydial genus specific, and cross-reactive. The epitopes recognized by these MAbs were localized within the primary amino acid sequence of hsp60 by immunoblotting against recombinant amino-terminal truncated hsp60 fusion polypeptides and then precisely mapped by use of overlapping synthetic peptides. The majority of the MAbs mapped to either the amino or the carboxyl termini of hsp60. Epitopes defining all three MAb reactivities mapped within amino-terminal residues 6 to 16. Genus-specific hsp60 MAbs mapped to epitopes located within this region and to residues 17 to 28 and 177 to 189. Antichlamydial hsp60 MAbs stained inclusions as effectively as MAbs specific for the major outer membrane protein. Homogeneous preparations of full-length recombinant chlamydial hsp60 and amino-terminal truncated recombinant hsp60 polypeptides were obtained by immunoabsorption chromatography with an hsp60 MAb reactive to the carboxyl terminus of the protein. Thus, the antichlamydial MAbs described here should be extremely useful for the specific immunodetection of hsp60 in tissues from individuals having different disease manifestations and for the purification of hsp60 or truncated hsp60 polypeptides for use in serologic and lymphocyte proliferation assays. The availability of these MAbs will facilitate studies to define more precisely the role of hsp60 in the immunopathogenesis of chlamydial disease. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NR 43 TC 69 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1992 VL 60 IS 6 BP 2288 EP 2296 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HX421 UT WOS:A1992HX42100021 PM 1375196 ER PT J AU FURTADO, GC SLOWIK, M KLEINMAN, HK JOINER, KA AF FURTADO, GC SLOWIK, M KLEINMAN, HK JOINER, KA TI LAMININ ENHANCES BINDING OF TOXOPLASMA-GONDII TACHYZOITES TO J774 MURINE MACROPHAGE CELLS SO INFECTION AND IMMUNITY LA English DT Article ID A-CHAIN; RECEPTOR; INTEGRIN; ATTACHMENT; SEQUENCE; ADHESION; IDENTIFICATION; PROTEIN; P1 AB We investigated the effects of the extracellular matrix proteins laminin and fibronectin on the attachment of tachyzoites of Toxoplasma gondii to the murine macrophage cell line J774. Laminin but not fibronectin increased parasite attachment to J774 cells in a dose-dependent fashion. Cyclic YIGSR, a laminin-derived peptide which inhibits laminin binding to the 32/67-kDa laminin-binding protein on host cells, blocked the laminin-mediated enhancement of parasite attachment. An antiserum to the 32/67-kDa laminin-binding protein also inhibited binding of parasites to J774 cells. These results, in conjunction with our previous observations (G. C. Furtado, F. L. Collins, and K. A. Joiner, submitted for publication), demonstrate that tachyzoites bearing surface laminin bind to multiple laminin receptors in attaching to different target cells. C1 YALE UNIV,SCH MED,INFECT DIS SECT,NEW HAVEN,CT 06510. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [R01-AI30060-01] NR 32 TC 70 Z9 70 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 JUN PY 1992 VL 60 IS 6 BP 2337 EP 2342 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HX421 UT WOS:A1992HX42100028 PM 1534073 ER PT J AU KOZIOL, DE KURTZMAN, G AYUB, J YOUNG, NS HENDERSON, DK AF KOZIOL, DE KURTZMAN, G AYUB, J YOUNG, NS HENDERSON, DK TI NOSOCOMIAL HUMAN PARVOVIRUS-B19 INFECTION - LACK OF TRANSMISSION FROM A CHRONICALLY INFECTED PATIENT TO HOSPITAL STAFF SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RED-CELL APLASIA; B19 PARVOVIRUS; HEREDITARY SPHEROCYTOSIS; ERYTHEMA-INFECTIOSUM; HEMOLYTIC-ANEMIA; B19-PARVOVIRUS INFECTION; EMERGING STORY; 5TH DISEASE; CRISIS; PREGNANCY AB OBJECTIVE: To assess the potential for nosocomial spread of parvovirus B19 from a chronically infected patient. DESIGN: Employees exposed to the index case and control (unexposed) employees were evaluated by baseline and follow up parvovirus B19 serologies and hematologic assessments, and completed baseline and follow up epidemiologic questionnaires. SETTING: A chronically infected patient was hospitalized on a hematology ward in a research referral hospital for 3.5 weeks prior to a diagnosis of parvovirus B19 infection and the institution of isolation precautions. METHODS: Sera were screened for parvovirus B19 DNA (dot blot analysis), and IgG and IgM anti-B 19 antibodies (capture immunoassay). Hematologic assessment included CBC, differential, and reticulocyte count. RESULTS: The index case had parvovirus B19 DNA at approximately 10(6) genome copies per ml of serum, elevated IgM and low levels of IgG B19 antibodies. Of the 21 exposed staff, 11 (52%) had IgG B19 antibodies and were immune; of the 8 unexposed staff, 6 (75%) had IgG B19 antibodies. No employees developed IgM B19 antibodies, B19 DNA, hematologic abnormalities, or clinical symptoms. CONCLUSIONS: In contrast to reports of documented nosocomial transmission of B19 parvovirus from patients in transient aplastic crisis, nosocomial transmission did not occur-even in the absence of isolation precautions-presumably from the lower level of B19 viremia in our chronically infected (rather than acutely infected) patient. C1 NHLBI,MOLEC DIS BRANCH,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. NHLBI,MOLEC DIS BRANCH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP KOZIOL, DE (reprint author), NHLBI,MOLEC DIS BRANCH,HOSP EPIDEMIOL SERV,BLDG 10,ROOM 4A 21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 68 TC 17 Z9 17 U1 0 U2 0 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 JUN PY 1992 VL 13 IS 6 BP 343 EP 348 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA HY768 UT WOS:A1992HY76800006 PM 1619271 ER PT J AU INSEL, TR AF INSEL, TR TI NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER - A REVIEW SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID CLOMIPRAMINE RP INSEL, TR (reprint author), NIMH,NEUROPHYSIOL LAB,NIH ANIM CTR,BLDG 110,ELMER SCH RD,POOLESVILLE,MD 20837, USA. NR 10 TC 17 Z9 17 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JUN PY 1992 VL 7 SU 1 BP 31 EP 33 DI 10.1097/00004850-199206001-00008 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA JG476 UT WOS:A1992JG47600007 PM 1517554 ER PT J AU BEVERLY, B KANG, SM LENARDO, MJ SCHWARTZ, RH AF BEVERLY, B KANG, SM LENARDO, MJ SCHWARTZ, RH TI REVERSAL OF INVITRO T-CELL CLONAL ANERGY BY IL-2 STIMULATION SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE COSTIMULATION; LIMITING DILUTION ANALYSIS; PRECURSOR FREQUENCY; LYMPHOKINE PRODUCTION ID LYMPHOCYTES-T; SELF-TOLERANCE; ANTIGEN; INDUCTION; UNRESPONSIVENESS; PROLIFERATION; INTERLEUKIN-2; INACTIVATION; ACTIVATION; ANTIBODY AB Stimulation of a normal type I mouse T helper cell clone (T(H)1) with concanavalin A in the absence of antigen presenting cells (APC) in vitro results in the induction of a hyporesponsive state known as T cell clonal anergy. This state is characterized by a decrease in proliferation following stimulation with antigen and APC resulting from a decrease in the production of IL-2. Production of the lymphokines IL-3/granulocyte macrophage colony stimulating factor and IFN-gamma is also reduced, although to a lesser degree. Stimulation of such anergic cells with IL-2 results in proliferation and a complete reversal of the state. We demonstrate that this reversal is not due to the outgrowth of a subpopulation of cells that had escaped anergy induction, but rather occurs in all the cells. Anergy also dissipated spontaneously, although much more slowly, in the absence of T cell antigen receptor occupancy. Finally, we show that a similar state can be produced by normal activation with antigen and APC if IL-2 and other factors are removed at 16-20 h. These results indicate that the anergic state is not a permanent change in the T(H)1 cell. Anergy induction appears to be a consequence of the inability of the cell to divide extensively following stimulation through the antigen-specific receptor. We propose a model to explain these results in terms of a relatively stable negative regulatory factor. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP BEVERLY, B (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 34 TC 326 Z9 329 U1 1 U2 7 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 JUN PY 1992 VL 4 IS 6 BP 661 EP 671 DI 10.1093/intimm/4.6.661 PG 11 WC Immunology SC Immunology GA JA071 UT WOS:A1992JA07100005 PM 1616898 ER PT J AU GREEN, KJ VIRATA, MLA ELGART, GW STANLEY, JR PARRY, DAD AF GREEN, KJ VIRATA, MLA ELGART, GW STANLEY, JR PARRY, DAD TI COMPARATIVE STRUCTURAL-ANALYSIS OF DESMOPLAKIN, BULLOUS PEMPHIGOID ANTIGEN AND PLECTIN - MEMBERS OF A NEW GENE FAMILY INVOLVED IN ORGANIZATION OF INTERMEDIATE FILAMENTS SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE INTERMEDIATE FILAMENTS; DESMOSOMES; HEMIDESMOSOMES ID HEMIDESMOSOMES; TROPOMYOSIN; DESMOSOMES; PROTEINS; CDNA AB Desmoplakins (DP) and bullous pemphigoid antigen (BPA) are major plaque components of the desmosome and hemidesmosome, respectively. These cell adhesion structures are both associated intimately with the intermediate filament (IF) network. Structural analyses of DP and BPA sequences have indicated that these molecules are likely to form extended dumbbell-shaped dimers with a central rod and globular end domains. Recent sequence data have indicated that the N-terminal domains of both DP and BPA (like their C-terminal domains) are highly relate& the former contain regions of heptad repeats that are predicted to form several alpha-helical bundles. Comparisons of DP and BPA protein sequences with that of plectin (PL), a 466 kDa IF-associated protein, have also revealed large scale homology. Identities between their N-terminal domains are: DP:BPA = 35%, DP:PL = 32%, BPA:PL = 40%, suggesting that BPA is more closely related to PL than DP in this region. In the C-terminal domains, which contain a 38-residue repeating motif, however, DP and PL are closer relatives (identities: DP:BPA = 38%, BPA:PL = 40%, DP:PL = 49%). The central domains of all three proteins have extensive heptad repeat substructure, express the same periodic distribution of charged residues, and are predicted to form two-stranded alpha-helical coiled-coil ropes. These observations suggest that DP, BPA and PL belong to a new gene family encoding proteins involved in IF organization. C1 NORTHWESTERN UNIV,SCH MED,CTR CANC,CHICAGO,IL 60611. NIH,DERMATOL BRANCH,BETHESDA,MD 20892. MASSEY UNIV,DEPT PHYS & BIOPHYS,PALMERSTON NORTH,NEW ZEALAND. RP GREEN, KJ (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. FU NICHD NIH HHS [HD24430] NR 32 TC 156 Z9 156 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD JUN PY 1992 VL 14 IS 3 BP 145 EP 153 DI 10.1016/S0141-8130(05)80004-2 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA HW552 UT WOS:A1992HW55200004 PM 1390446 ER PT J AU GILLIGAN, DM STEWART, R CHAN, WL OAKLEY, CM JOSHI, J KRIKLER, S AF GILLIGAN, DM STEWART, R CHAN, WL OAKLEY, CM JOSHI, J KRIKLER, S TI XAMOTEROL IN HYPERTROPHIC CARDIOMYOPATHY - EFFECTS ON DIASTOLIC FUNCTION AND HEART-RATE SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE HYPERTROPHIC CARDIOMYOPATHY; BETA-1-ADRENOCEPTOR; XAMOTEROL; DIASTOLIC FUNCTION; HOLTER; AMBULATORY ELECTROCARDIOGRAPHIC MONITORING ID BETA-1-ADRENOCEPTOR PARTIAL AGONIST; ADRENOCEPTOR PARTIAL AGONIST; CLINICAL MANIFESTATIONS; MYOCARDIAL-INFARCTION; PATHO-PHYSIOLOGY; IMPROVEMENT; RELAXATION; THERAPY; INTERRELATIONS; DYSFUNCTION AB The aims of this study were to determine the effects of the partial beta-1-adrenergic agonist, xamoterol, on diastolic function and ambulatory heart rate in hypertrophic cardiomyopathy. Eleven patients with non-obstructive hypertrophic cardiomyopathy were studied with cross-sectional and Doppler echocardiography and 24-h Holter monitoring before and after a single intravenous dose of xamoterol. Resting heart rate (mean +/- SD) increased from 76 +/- 16 before, to 83 +/- 15 beats/ min 15 min after xamoterol, p=0.03. In the 4-h period after xamoterol, maximum heart rate was reduced (127 +/- 21 to 112 +/- 19, p=0.01) and minimum heart increased (60 +/- 16 to 67 +/- 17, p=0.04) compared to the same 4-h period of the previous day. There were no significant changes in cross-sectional or Doppler echocardiographic measurements of left ventricular function following xamoterol. Xamoterol stabilises the heart rate in hypertrophic cardiomyopathy. The absence of a significant effect on Doppler measurements does not preclude a beneficial effect on diastolic function. This initial study suggests that xamoterol should be further investigated as a new medical therapy for hypertrophic cardiomyopathy. C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT MED CLIN CARDIOL,LONDON W12 0HS,ENGLAND. RP GILLIGAN, DM (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD JUN PY 1992 VL 35 IS 3 BP 377 EP 386 DI 10.1016/0167-5273(92)90237-W PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HY550 UT WOS:A1992HY55000012 PM 1351887 ER PT J AU FORMAN, MR YAO, SX GRAUBARD, BI QIAO, YL MCADAMS, M MAO, BL TAYLOR, PR AF FORMAN, MR YAO, SX GRAUBARD, BI QIAO, YL MCADAMS, M MAO, BL TAYLOR, PR TI THE EFFECT OF DIETARY-INTAKE OF FRUITS AND VEGETABLES ON THE ODDS RATIO OF LUNG-CANCER AMONG YUNNAN TIN MINERS SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID VITAMIN-A; RISK; CONSUMPTION; CAROTENE; HAWAII AB All newly diagnosed cases of lung cancer (N = 183) among male tin miners of Yunnan Province, China and age-sex matched occupational controls (N = 183 aged 45-79 years) were interviewed within 3 months following cancer diagnosis. The questionnaire included information about usual adult diet as well as employment and smoking histories. Over 95% of cases and controls were current smokers. The 27-item food frequency questionnaire included 11 fruits and vegetables rich in vitamin A and/or carotenoids. The effect of dietary intake of fruits and vegetables on risk of lung cancer was examined with adjustment for exposures to radon, arsenic, and smoking as previously documented risk factors for lung cancer. Tin miners with reduced intake of yellow and light green vegetables had statistically significant increased odds ratios (OR) of lung cancer (OR = 2.26 and OR = 2.39 for the lowest two quartiles of intake; P value for trend = 0.02) among cases compared with controls after multiple logistic regression adjustment for covariates; and this relationship was monotonic. Tin miners with reduced intake of tomatoes had statistically significant increased adjusted OR of lung cancer (OR = 2.64, OR = 3.09, OR = 2.36 for the three lowest quartiles of intake; P value for trend = 0.04). This is the first study to demonstrate a protective effect of vegetable intake versus the strong effects of smoking and occupational exposures on lung cancer risk. C1 INFORMAT MANAGEMENT SYST,SILVER SPRING,MD. YUNNAN TIN MINER CORP,GEJIU,PEOPLES R CHINA. RP FORMAN, MR (reprint author), NCI,DCPL,CPRP,CANC PREVENT STUDIES BRANCH,EXECUT PLAZA N,ROOM 211C,BETHESDA,MD 20892, USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 17 TC 39 Z9 41 U1 1 U2 4 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 JUN PY 1992 VL 21 IS 3 BP 437 EP 441 DI 10.1093/ije/21.3.437 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JB408 UT WOS:A1992JB40800001 PM 1634303 ER PT J AU BOLIG, R PRICE, CS ONEILL, PL SUOMI, SJ AF BOLIG, R PRICE, CS ONEILL, PL SUOMI, SJ TI SUBJECTIVE ASSESSMENT OF REACTIVITY LEVEL AND PERSONALITY-TRAITS OF RHESUS-MONKEYS SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE MACACA-MULATTA; SUBJECTIVE; ASSESSMENT; REACTIVITY; PERSONALITY AB The purposes of this study are to determine whether subjective assessment of reactivity level in rhesus macaques, between 1 and 14 years old, is related to assessment of personality traits and whether a configuration of personality traits most salient for assessment of reactivity can be defined. Results indicate that subjective assessment of reactivity is complementary to that of personality traits. Interrater reliability and convergent validity are establishea. Principal-component and discriminant analyses of the present data show that 10 personality traits can assign all subjects to reactivity level, but as few as 3 traits may be sufficient. C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RP BOLIG, R (reprint author), OHIO STATE UNIV,DEPT FAMILY RELAT & HUMAN DEV,COLUMBUS,OH 43210, USA. NR 16 TC 55 Z9 55 U1 1 U2 8 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD JUN PY 1992 VL 13 IS 3 BP 287 EP 306 DI 10.1007/BF02547817 PG 20 WC Zoology SC Zoology GA JA862 UT WOS:A1992JA86200003 ER PT J AU BORNSTEIN, MH AF BORNSTEIN, MH TI CROSS-CULTURAL PERSPECTIVES ON PARENTING SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 1992 VL 27 IS 3-4 BP 4 EP 4 PG 1 WC Psychology, Multidisciplinary SC Psychology GA JF420 UT WOS:A1992JF42000017 ER PT J AU VYT, A BORNSTEIN, MH AF VYT, A BORNSTEIN, MH TI EARLY BILINGUAL EDUCATION AND LEFT-HANDEDNESS AS POTENTIAL RISK-FACTORS FOR LANGUAGE-ACQUISITION SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 STATE UNIV GHENT,B-9000 GENT,BELGIUM. NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 1992 VL 27 IS 3-4 BP 215 EP 215 PG 1 WC Psychology, Multidisciplinary SC Psychology GA JF420 UT WOS:A1992JF42001122 ER PT J AU SHAW, GA GIAMBRA, LM AF SHAW, GA GIAMBRA, LM TI TASK-UNRELATED-THOUGHTS OF COLLEGE-STUDENTS DIAGNOSED AS HYPERACTIVE IN CHILDHOOD SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 GEORGETOWN COLL,GEORGETOWN,KY. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 1992 VL 27 IS 3-4 BP 390 EP 390 PG 1 WC Psychology, Multidisciplinary SC Psychology GA JF420 UT WOS:A1992JF42002093 ER PT J AU KELTY, EJ AF KELTY, EJ TI BEHAVIORAL CONTRIBUTIONS TO ENVIRONMENTAL-ISSUES SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIMH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 1992 VL 27 IS 3-4 BP 610 EP 610 PG 1 WC Psychology, Multidisciplinary SC Psychology GA JF420 UT WOS:A1992JF42003246 ER PT J AU KELTY, MF AF KELTY, MF TI FOCUSING RESEARCH ON AGING SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 1992 VL 27 IS 3-4 BP 622 EP 622 PG 1 WC Psychology, Multidisciplinary SC Psychology GA JF420 UT WOS:A1992JF42003308 ER PT J AU SIRIGU, P SHEN, RL DASILVA, PP AF SIRIGU, P SHEN, RL DASILVA, PP TI HUMAN MEIBOMIAN GLANDS - THE ULTRASTRUCTURE OF ACINAR-CELLS AS VIEWED BY THIN-SECTION AND FREEZE-FRACTURE TRANSMISSION ELECTRON MICROSCOPIES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE (HUMAN) MEIBOMIAN GLAND; SEBACEOUS GLAND; HOLOCRINE SECRETION ID MALE-PATTERN BALDNESS; SEBACEOUS GLANDS; LIPIDS; SCALP; SKIN AB Heightened interest in meibomian glands dysfunction prompted the authors to examine the ultrastructure of the glandular epithelium in specimens of surgical origin, by thin section and freeze-fracture electron microscopies. In meibomian glands, the morphology and ultrastructure of acinar cells varies considerably according to their stage of holocrine differentiation. This study shows close interdependence between fat droplets and Golgi apparatus or endoplasmic reticulum. As the cells initiate their differentiation, the smooth endoplasmic reticulum and the Golgi apparatus become prominent and the first small lipid droplets appear in the cytoplasm. When fractured through a plane close to their surface, lipid droplets appear onion-like structured, ie made up of a variable number of irregular shaped concentric lamellae. This lamellar organization suggests that membranes are not only involved in synthesis, but also that some of their components are incorporated in the fat droplets. The authors conclude that human meibomian glands are a holocrine glandular complex that, despite great differences in type and location, present basic similarities with sebaceous glands. C1 NCI,FREDERICK CANC RES & DEV CTR,MEMBRANE BIOL SECT,MATH BIOL LAB,BLDG 538,ROOM 104,FREDERICK,MD 21702. UNIV CAGLIARI,DEPT CYTOMORPHOL,I-09100 CAGLIARI,ITALY. RI Shen, Rulong/E-4079-2011 NR 30 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1992 VL 33 IS 7 BP 2284 EP 2292 PG 9 WC Ophthalmology SC Ophthalmology GA HZ007 UT WOS:A1992HZ00700028 PM 1607240 ER PT J AU GUO, HG CHANG, KSS AF GUO, HG CHANG, KSS TI A VERTICALLY TRANSMITTED HIV-1 GAG-SUBTYPE VARIANT DETECTED IN TAIWAN SO JAPANESE JOURNAL OF MEDICAL SCIENCE & BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; GENETIC-VARIATION; PERIPHERAL-BLOOD; TYPE-1; AIDS; NEUTRALIZATION; INFECTION; INFANTS; INVIVO AB We used polymerase chain reaction (PCR) to amplify a segment, about 560 base pairs (bp), of HIV-1 gag DNA prepared from peripheral blood mononuclear cells of a seropositive Taiwanese pair of mother and infant. TM-1 and TC-1 clones of PCR-amplified DNA derived from the mother and infant, respectively, showed a 94.5% homology with each other. However, the TM-1 and TC-1 sequences exhibited lower degrees of homology, i.e. only 85.1% and 85.8%, respectively, with the corresponding gag segment of a North American HIV-1 subtype (HXB2), and 86.4% and 87.0%, respectively, with that of a Zairean HIV-1 subtype (Z2Z6). The divergence of TM-1 and TC-1 sequences from those of HXB2 and Z2Z6 is particularly prominent in the first (5' proximal) 200 bp of the cloned DNA segment, involving transitions more frequently than transversions. Two additional clones TM-2 and TC-2 derived from the mother and infant were sequenced for the first 200 bp. These four clones showed a high degree of homology (94.7-97.5%) among themselves, providing an evidence for transmission of the virus from the mother to the infant. These findings show the epidemiological value of PCR, and indicate the presence of a gag subtype of HIV-1 which is distinct from both the North American and Zairean subtypes according to the phylogenetic tree constructed. C1 CHANG GUNG MED COLL,GRAD INST CLIN MED,TAOYUAN,TAIWAN. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 26 TC 0 Z9 0 U1 0 U2 0 PU NATL INST HEALTH PI TOKYO PA C/O JPN J MED SCI BIOL, 23-1, TOYAMA 1-CHOME, SHINJUKU-KU, TOKYO 162, JAPAN SN 0021-5112 J9 JPN J MED SCI BIOL JI Jpn. J. Med. Sci. Biol. PD JUN PY 1992 VL 45 IS 3 BP 127 EP 136 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA KD800 UT WOS:A1992KD80000003 PM 1291763 ER PT J AU IGARASHI, Y LUNDGREN, JD DOERFLER, ME SHELHAMER, JH KALINER, MA WHITE, MV AF IGARASHI, Y LUNDGREN, JD DOERFLER, ME SHELHAMER, JH KALINER, MA WHITE, MV TI HUMAN NEUTROPHIL-DERIVED HISTAMINE-RELEASING ACTIVITY (HRA-N) CAUSES THE RELEASE OF SEROTONIN BUT NOT ARACHIDONIC-ACID METABOLITES FROM RAT BASOPHILIC LEUKEMIA-CELLS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE NEUTROPHIL; HISTAMINE-RELEASING FACTOR; BASOPHIL; RAT BASOPHILIC LEUKEMIA CELL; SEROTONIN; ARACHIDONIC ACID; PROSTAGLANDIN; LEUKOTRIENE ID LUNG MAST-CELLS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; SLOW REACTING SUBSTANCE; HUMAN MONONUCLEAR-CELLS; MOUSE BONE-MARROW; LATE-PHASE; DIFFERENTIAL RELEASE; ANTIGEN CHALLENGE; LEUKOTRIENE C-4; HUMAN AIRWAYS AB The effects of neutrophil-derived histamine-releasing activity (HRA-N) on arachidonic acid (AA) metabolism is unknown. Human basophils exposed to HRA-N released 25% of total histamine but no leukotriene C4 (LTC4). To confirm this phenomenon, rat basophilic leukemia (RBL) cells were exposed to HRA-N as well as anti-IgE, or calcium ionophore A23187. RBL cells incubated with A23187 released 44% of available serotonin and 59 and 124 pmol/10(6) cells of prostaglandin D2 (PGD2) and LTC4, respectively. Anti-IgE stimulation resulted in 34% serotonin release and the generation of 34 pmol PGD, per 10(6) cells and 72 pmol LTC4 per 10(6) cells. In contrast, HRA-N (2 U/ml) induced 20% serotonin release, 4 pmol PGD, per 10(6) cells, and 0.6 pmol LTC4 per 10(6) cells. Neither increasing the dose nor the incubation time of HRA-N enhanced the generation of AA metabolite. Additionally, the spectrum of AA metabolites generated by RBL cells in response to those agents was examined by reverse-phase high-performance liquid chromatography. RBL cells stimulated with A23187 released PGD2, LTB4, and its isomers, LTC4, and 5-hydroxyeicosatetraenoic acid. In contrast, HRA-N stimulation resulted in only minimal PGD2 generation and no other discernable AA metabolites. Thus, HRA-N causes selective release of serotonin without inducing AA metabolites. These data suggest that HRA-N activates mast cells through a unique pathway. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11C207,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. OI Lundgren, Jens/0000-0001-8901-7850 NR 54 TC 5 Z9 5 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1992 VL 89 IS 6 BP 1085 EP 1097 DI 10.1016/0091-6749(92)90292-A PG 13 WC Allergy; Immunology SC Allergy; Immunology GA HZ748 UT WOS:A1992HZ74800003 PM 1376734 ER PT J AU OKAYAMA, M BARANIUK, JN HAUSFELD, JN MERIDA, M KALINER, MA AF OKAYAMA, M BARANIUK, JN HAUSFELD, JN MERIDA, M KALINER, MA TI CHARACTERIZATION AND AUTORADIOGRAPHIC LOCALIZATION OF HISTAMINE H1 RECEPTORS IN HUMAN NASAL TURBINATES SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE HUMAN NASAL MUCOSA; H1 RECEPTORS; [3H]PYRILAMINE; AUTORADIOGRAPHY; HISTAMINE; VASCULAR PERMEABILITY; NASAL SECRETION ID H-1 RECEPTORS; SMOOTH-MUSCLE; BINDING;