FN Thomson Reuters Web of Science™ VR 1.0 PT J AU ZAHN, TP PICKAR, D HAIER, RJ AF ZAHN, TP PICKAR, D HAIER, RJ TI EFFECTS OF CLOZAPINE, FLUPHENAZINE, AND PLACEBO ON REACTION-TIME MEASURES OF ATTENTION AND SENSORY DOMINANCE IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE ATTENTION; REACTION TIME; SENSORY DOMINANCE; CLOZAPINE; HALLUCINATION; (SCHIZOPHRENIA) ID VISUAL DOMINANCE; PERFORMANCE; SYMPTOMS; DISORDER AB Two reaction time (RT) paradigms were used to study clozapine's effects on sustained and selective attention compared to fluphenazine and placebo in 25 chronic schizophrenic patients. Sensory dominance was studied via simple and choice RTs to lights and tones, and on double-stimulus trials in which the two stimuli were presented simultaneously. Although 8 of the 25 patients could not perform the RT tasks when taking placebo, there were no effects of clozapine on simple or choice RT compared to placebo or fluphenazine. Subjects on all 3 treatments showed visual dominance: faster RT to lights than to tones on choice and double-stimulus trials. However, clozapine reduced this by means of a selective increase in RT to lights. Clozapine reduced failures to respond to the tone on double-stimulus trials. This was shown to be due to reductions in hallucinations. Clozapine does not generally improve attention, but it may increase the ability of schizophrenic persons to process nondominant or unattended stimuli possibly by increasing the efficiency of resource allocation. This may be partially mediated by a reduction in hallucinations. C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. UNIV CALIF IRVINE,COLL MED,DEPT PSYCHIAT & HUMAN BEHAV,IRVINE,CA 92717. RP ZAHN, TP (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,RM 4C110,BETHESDA,MD 20892, USA. NR 28 TC 50 Z9 50 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 1994 VL 13 IS 2 BP 133 EP 143 DI 10.1016/0920-9964(94)90094-9 PG 11 WC Psychiatry SC Psychiatry GA PE016 UT WOS:A1994PE01600005 PM 7986770 ER PT J AU ELKASHEF, AM ISSA, F GINDRAW, A WYATT, RJ KIRCH, DG AF ELKASHEF, AM ISSA, F GINDRAW, A WYATT, RJ KIRCH, DG TI EFFECTS OF WATER LOADING IN SCHIZOPHRENIC-PATIENTS WITH POLYDIPSIA-HYPONATREMIA - AN MRI PILOT-STUDY SO SCHIZOPHRENIA RESEARCH LA English DT Article DE POLYDIPSIA; MRI; (SCHIZOPHRENIA) ID CT-BRAIN-SCAN; INTOXICATION AB We conducted an MRI pilot study of three schizophrenic patients with the syndrome of polydipsia-hyponatremia. Paired MRI scans were obtained at baseline and in the water-loaded state to study the acute effects of water loading and accompanying changes in serum sodium and osmolality on brain structures. We report the pilot data on the observed individual MRI changes of reduced volume of the lateral ventricles in all three patients, and the third ventricles in two patients, in the water-loaded state. These changes were not statistically significant possibly because of small sample size. C1 MED COLL GEORGIA,SCH MED,OFF DEAN,AUGUSTA,GA 30912. RP ELKASHEF, AM (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 1994 VL 13 IS 2 BP 169 EP 172 DI 10.1016/0920-9964(94)90098-1 PG 4 WC Psychiatry SC Psychiatry GA PE016 UT WOS:A1994PE01600009 PM 7986774 ER PT J AU ALDROUBI, A EDEN, M UNSER, M AF ALDROUBI, A EDEN, M UNSER, M TI DISCRETE SPLINE FILTERS FOR MULTIRESOLUTIONS AND WAVELETS OF L(2) SO SIAM JOURNAL ON MATHEMATICAL ANALYSIS LA English DT Article DE MULTIRESOLUTION; WAVELETS; SPLINES; SAMPLING; IDEAL FILTER; PYRAMID ID COMPACTLY SUPPORTED WAVELETS; STURM-LIOUVILLE PROBLEMS; LAGRANGE INTERPOLATION; ORTHONORMAL BASES; SAMPLING THEOREM; CUBIC-SPLINES; RECONSTRUCTION; REPRESENTATION; CONVERGENCE; DESIGN AB The authors consider the problem of approximation by B-spline functions, using a norm compatible with the discrete sequence-space l2 instead of the usual norm L2. This setting is natural for digital signal/image processing and for numerical analysis. To this end, sampled B-splines are used to define a family of approximation spaces S(m)n subset-of l2. For n odd, S(m)n is partitioned into sets of multiresolution and wavelet spaces Of l2. It is shown that the least squares approximation in S(m)n of a sequence s is-an-element-of l2 is obtained using translation-invariant filters. The authors study the asymptotic properties of these filters and provide the link with Shannon's sampling procedure. Two pyramidal representations of signals are derived and compared: the l2-optimal and the stepwise l2-optimal pyramids, the advantage of the latter being that it can be computed by the repetitive application of a single procedure. Finally, a step by step discrete wavelet transform Of l2 is derived that is based on the stepwise optimal representation. As an application, these representations are implemented and compared with the Gaussian/Laplacian pyramids that are widely used in computer vision. RP NIH, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 47 TC 39 Z9 41 U1 0 U2 1 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1410 EI 1095-7154 J9 SIAM J MATH ANAL JI SIAM J. Math. Anal. PD SEP PY 1994 VL 25 IS 5 BP 1412 EP 1432 DI 10.1137/S0036141092234086 PG 21 WC Mathematics, Applied SC Mathematics GA PD760 UT WOS:A1994PD76000010 ER PT J AU YAROSLAVSKY, L EDEN, M AF YAROSLAVSKY, L EDEN, M TI CORRELATIONAL ACCUMULATION AS A METHOD FOR SIGNAL RESTORATION SO SIGNAL PROCESSING LA English DT Article DE CORRELATION; LOCALIZATION ACCURACY; SIGNAL AVERAGING; SIGNAL REGISTRATION; SIGNAL RESTORATION AB This work analyses the method of correlational accumulation (averaging) of a set of multiple copies of a signal from the same object arbitrarily displaced with relation to one another and observed in a mixture with additive signal independent sensor noise in which the signal displacements are measured by localization of maximum of the signal cross-correlation function. Three main problems are addressed and investigated both analytically and by computer simulation: optimality of the correlational accumulation method, signal distortions which originate from the signal registration errors and noise reduction capability of the correlational accumulation as a function of signal-to-noise ratio in the observed signal-plus-noise realizations. RP YAROSLAVSKY, L (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1684 J9 SIGNAL PROCESS JI Signal Process. PD SEP PY 1994 VL 39 IS 1-2 BP 89 EP 106 DI 10.1016/0165-1684(94)90126-0 PG 18 WC Engineering, Electrical & Electronic SC Engineering GA PM211 UT WOS:A1994PM21100007 ER PT J AU SCHOOLER, C AF SCHOOLER, C TI A WORKING CONCEPTUALIZATION OF SOCIAL-STRUCTURE - MERTONIAN ROOTS AND PSYCHOLOGICAL AND SOCIOCULTURAL RELATIONSHIPS SO SOCIAL PSYCHOLOGY QUARTERLY LA English DT Article ID EXCHANGE NETWORKS; JAPAN; POWER AB Using a small set of interlocking definitions, this paper presents a generally applicable conceptualization of social structure developed from recollections of Merton's late-1950s formulation. A brief review of the literature supports the view that the proposed conceptualization provides sociological researchers with a relatively simple and logically consistent overall framework, generally continuous with past theorizing, in which to place their own findings. The paper pays particular attention to how social structures are related causally and epistemologically to more micro-level psychological and more macrolevel sociocultural phenomena. Theoretical considerations and empirical evidence suggest a decrease in the likelihood and speed of change as we move from psychological- to social structural- to sociocultural-level phenomena. Although they require proof in each instance, these postulated differences in the relative speed with which psychological-, social structural-, and sociocultural-level phenomena tend to affect each other provide a new and potentially useful tool for unraveling the knotted causal connections among these different-level phenomena. RP SCHOOLER, C (reprint author), NIMH,LSES,ROOM B1-A-14,FED BLDG,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 55 TC 13 Z9 13 U1 0 U2 1 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036-2981 SN 0190-2725 J9 SOC PSYCHOL QUART JI Soc. Psychol. Q. PD SEP PY 1994 VL 57 IS 3 BP 262 EP 273 DI 10.2307/2786880 PG 12 WC Psychology, Social SC Psychology GA PT527 UT WOS:A1994PT52700008 ER PT J AU SCHOOLER, C SCHOENBACH, C AF SCHOOLER, C SCHOENBACH, C TI SOCIAL-CLASS, OCCUPATIONAL-STATUS, OCCUPATIONAL SELF-DIRECTION, AND JOB INCOME - A CROSS-NATIONAL EXAMINATION SO SOCIOLOGICAL FORUM LA English DT Article DE SOCIAL CLASS; OCCUPATIONAL STATUS; SELF-DIRECTION; JOB INCOME; CROSS-NATIONAL ID EXPERIENCE; INEQUALITY; JAPAN AB This paper evaluates the relationships of social class position, occupational status, and occupational self-direction to job income in three modern industrial societies, the United States, Japan, and Poland. In doing so, it goes beyond Wright and Perrone's analysis of 1977, which sought to establish the importance of social class by comparing the relative power with which occupational status and social class, defined in terms of relationship to the means of production, predict income. In carrying out analyses, we have also had to face the basic sociological issue of the nature and measurement of occupational status and have adopted a confirmatory factor analytic approach to the problem. Our substantive findings show that social class position has its strongest effect on income in Poland, and occupational self-direction also has an uniquely strong effect there. The singular importance of occupational status in Japan is noted and contrasted with the United States, where occupational status, social class, and education all have significant independent effects on job income. RP SCHOOLER, C (reprint author), NIMH,SOCIOENVIRONM STUDIES LAB,FED BLDG,ROOM B1 A14,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 48 TC 11 Z9 11 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0884-8971 J9 SOCIOL FORUM JI Sociol. Forum PD SEP PY 1994 VL 9 IS 3 BP 431 EP 458 DI 10.1007/BF01466317 PG 28 WC Sociology SC Sociology GA PJ003 UT WOS:A1994PJ00300006 ER PT J AU ROCCHI, M ARCHIDIACONO, N ANTONACCI, R FINELLI, P DAIUTO, L CARBONE, R LINDSAY, E BALDINI, A AF ROCCHI, M ARCHIDIACONO, N ANTONACCI, R FINELLI, P DAIUTO, L CARBONE, R LINDSAY, E BALDINI, A TI CLONING AND COMPARATIVE MAPPING OF RECENTLY EVOLVED HUMAN-CHROMOSOME 22-SPECIFIC ALPHA-SATELLITE DNA SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Note ID SEQUENCE; SUBFAMILIES; HYBRIDIZATION; ORGANIZATION AB We have isolated and characterized a new alphoid probe, named p190.22. Its chromosomal location was investigated using fluorescence in situ hybridization. Under high stringency conditions p190.22 recognizes specifically the centromere of chromosome 22. A chromosome 22-specific alphoid subset has been previously reported in the literature (p22/1:2.1). The pal tial sequence and the genomic organization comparison strongly suggests that they recognize distinct subsets both specific for chromosome 22. The comparative mapping of probes p190.22 and p22/1:2.1 on chimpanzee (PTR and PPA) and gorilla (GGO) chromosomes was investigated The two probes showed different hybridization results. p190.22, in particular, did not show any hybridization signal in these three species, subggesting a recent evolution. C1 IST ANAT UMANA NORMALE,CATTEDRA ISTOL & EMBRIOL,I-41100 MODENA,ITALY. NIH,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT HUMAN & MOLEC GENET,HOUSTON,TX 77030. BAYLOR COLL MED,CTR HUMAN GENOME,HOUSTON,TX 77030. RP ROCCHI, M (reprint author), UNIV BARI,IST GENET,VIA AMENDOLA 165-A,I-70126 BARI,ITALY. RI genes, anthony/F-2541-2012; Antonacci, Rachele/C-5635-2013; Finelli, Palma/A-3578-2016; OI Antonacci, Rachele/0000-0002-5601-1118; Finelli, Palma/0000-0001-8464-6906; archidiacono, nicoletta/0000-0002-1439-9521 FU NHGRI NIH HHS [HG00210] NR 19 TC 19 Z9 19 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD SEP PY 1994 VL 20 IS 5 BP 443 EP 448 DI 10.1007/BF02257462 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA QE099 UT WOS:A1994QE09900010 PM 7825067 ER PT J AU SANTUCCI, MA PIERCE, JH ZANNINI, S FORTUNA, A FREZZA, G BABINI, L ROSENSTEIN, MM GREENBERGER, JS AF SANTUCCI, MA PIERCE, JH ZANNINI, S FORTUNA, A FREZZA, G BABINI, L ROSENSTEIN, MM GREENBERGER, JS TI ERYTHROPOIETIN INCREASES THE RADIORESISTANCE OF A CLONAL HEMATOPOIETIC PROGENITOR-CELL LINE EXPRESSING A TRANSGENE FOR THE ERYTHROPOIETIN RECEPTOR SO STEM CELLS LA English DT Article DE ERYTHROPOIETIN; HEMATOPOIETIC CELLS; RADIATION REPAIR ID LOW-DOSE-RATE; COLONY-STIMULATING FACTORS; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION; RADIATION-RESISTANCE; IONIZING-RADIATIONS; CYCLE PROGRESSION; SURVIVAL; PROTEIN; ONCOGENES AB Erythropoietin(Epo) is a serum glycoprotein growth factor required for the survival, proliferation and differentiation of committed erythroid progenitor cells. In the present study, we sought to determine whether the action of Epo via its receptor is also implicated in the repair of radiation-induced cell damage. Overexpression of the Epo receptor (Epo-R) was achieved as a result of transfection of the 32D cl 3 clonal hematopoietic cell line. These clonal lines allowed us to investigate the effects of Epo on the radiation sensitivity in vitro of a clonal murine hematopoietic progenitor cell line. Low level expression of Epo R on many hematopoietic cell types was thus circumvented. Ligand binding of Epo resulted in increased radioresistance of 32D cl 3 subclonal lines expressing the Epo-R transgene. The D-0 of 32D Epo-R cells at 1.49 Gy/min was 1.33 Gy and ($) over bar n was 1.39. The D-0 of parental clonal cell line 32D cl 3 cells at 1.49 Gy/min was 1.36 Gy and ($) over bar n was 1.39. In contrast, at the low dose rate of 0.0595 Gy/min, the D-0 of 32D Epo-R cells was 2.0 Gy and ($) over bar n was 1.24, while parental clonal line 32D cl 3 showed a D-0 of 1.35 Gy and ($) over bar n was 1.39. The increased radioresistance was statistically significant at low dose rate (p < 0.05). Combined exposure to Epo and interleukin 3 (IL-3) increased proliferation of 32D Epo-R cells but did not induce a detectable further increase in radioresistance. Temporal dissociation between growth factor-activated tyrosine phosphorylation of intracellular substrates, and the radioprotective effect was observed. We searched for possible involvement of an Epo-mediated alteration of cell cycle progression as a cause of radioprotection. A 24-h exposure to Epo alone or in combination with IL-3 did not significantly expand the relative size of the cell population in the relatively radioresistant S phase. The present results indicate that Epo can be considered as one of the group of cytokines that demonstrates a radioprotective effect in vitro. Administration of Epo may have a role in some radiotherapy protocols where specific erythroid hematopoietic toxicity is expected. C1 UNIV PITTSBURGH, SCH MED, DEPT RADIAT ONCOL, PITTSBURGH, PA 20892 USA. UNIV BOLOGNA, SCH MED, IST CANCEROL, I-80121 BOLOGNA, ITALY. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD USA. STAZ ZOOL ANTON DOHRN, NAPLES, ITALY. UNIV BOLOGNA, SCH MED, IST RADIOTERAPIA, BOLOGNA, ITALY. RI Zannini, Mariastella/I-1735-2012 FU NCI NIH HHS [CA39851]; NIDCR NIH HHS [DE08798] NR 35 TC 10 Z9 10 U1 1 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 1994 VL 12 IS 5 BP 506 EP 513 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA PE523 UT WOS:A1994PE52300006 PM 7804124 ER PT J AU POGUN, S DAWSON, V KUHAR, MJ AF POGUN, S DAWSON, V KUHAR, MJ TI NITRIC-OXIDE INHIBITS H-3 GLUTAMATE TRANSPORT IN SYNAPTOSOMES SO SYNAPSE LA English DT Article DE H-3 GLU; NITRIC OXIDE; SYNAPTOSOMES; GLUTAMATE UPTAKE; GLUTAMATE TRANSPORT ID LONG-TERM POTENTIATION; GLUTAMATE NEUROTOXICITY; CYCLIC-GMP; NERVOUS-SYSTEM; BRAIN; MESSENGER; NEUROTRANSMITTER; ENHANCEMENT; CULTURES; CELLS AB H-3-glutamate (GLU) uptake was measured in hippocampal synaptosomes from rat brain. Addition of sodium nitroprusside (SNP) (Sodium nitroferricyanide), a generator of nitric oxide (NO), produced a time-, temperature-, and dose-dependent inhibition of H-3-GLU uptake. The inhibition was due to changes in both Kd and Vmax of GLU uptake, and it was at least partially reversible upon washing. Addition of reduced hemoglobin (Hb), a substance that binds NO, prevented the SNP-induced depression of uptake. Potassium ferricyanide, a compound similar to SNP, did not cause a reduction in H-3-GLU uptake. Utilization of another generator of NO, S-nitroso-N-acetyl-penicillamine (SNAP), produced similar results as did NO itself. Decreases in uptake were also observed in the striatum and cerebellum. Similar treatments did not consistently affect H-3-norepinephrine (NE) uptake, suggesting some selectivity in the NO effect. Thus, the observed inhibition of H-3-GLU uptake appears to be produced by NO, and it may represent a novel type of transynaptic retrograde regulation of transport. If found in vivo, inhibition of uptake activity could also be involved in the toxic effects of NO, the neurotoxicity of glutamate, and other potential neuronal changes associated with NO such as hippocampal long-term potentiation. (C) 1994 Wiley-Liss, Inc. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RI Pogun, Sakire/A-5816-2010 NR 34 TC 92 Z9 92 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1994 VL 18 IS 1 BP 21 EP 26 DI 10.1002/syn.890180104 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PE144 UT WOS:A1994PE14400003 PM 7825120 ER PT J AU ALI, SF DAVID, SN NEWPORT, GD CADET, JL SLIKKER, W AF ALI, SF DAVID, SN NEWPORT, GD CADET, JL SLIKKER, W TI MPTP-INDUCED OXIDATIVE STRESS AND NEUROTOXICITY ARE AGE-DEPENDENT - EVIDENCE FROM MEASURES OF REACTIVE OXYGEN SPECIES AND STRIATAL DOPAMINE LEVELS SO SYNAPSE LA English DT Article DE AGING; DOPAMINE; MPTP; NEUROTOXICITY; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; STRIATUM ID HYDROXYL RADICAL GENERATION; MONOAMINE OXIDASE-B; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; 1-METHYL-4-PHENYLPYRIDINIUM MPP+; INTRACRANIAL MICRODIALYSIS; CATECHOLAMINE NEURONS; SUBSTANTIA NIGRA; TOXICITY; MICE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AB 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes marked depletion of dopamine (DA) levels and reduction in the activity of tyrosine hydroxylase (TH) in the nigrostriatal DA pathway. In the brain, the enzyme monoamine oxidase B converts MPTP to 1-methyl-4-phenylpyridinium (MPP(+)) which enters DA terminals via DA uptake sites. Within the DA terminals, MPP(+) blocks the mitochondrial complex I and causes ATP depletion. This is thought to be the main cause of MPTP-induced terminal degeneration. In addition, reactive oxygen species (ROS) generated after blockade of the complex I as well as those generated due to DA oxidation may participate in MPTP-induced dopaminotoxicity. The present study sought to determine if a single injection of a large dose of MPTP generates ROS. We also sought to determine if these changes as well as changes in DA levels were correlated and age-dependent. Toward that end, we have used C57/B6N male mice that were 22 days or 12 months old. These animals were injected with a single dose of MPTP (40 mg/kg, ip). Animals were sacrificed at various times after drug administration. MPTP produced no significant increase in ROS nor decreases in DA or HVA concentrations in the striatum of the younger mice. However, DOPAC concentrations were significantly decreased from 15-120 min after drug administration. In the older mice, MPTP caused significant increases in ROS from the beginning to the end of the study period. DA concentrations were decreased from 60 min onward. DOPAC concentrations were decreased significantly after 15-120 min while HVA concentrations were significantly increased after 60 and 120 min. These data demonstrate that in older mice, a single dose of MPTP can cause increases of ROS which were associated with subsequent decreases in DA concentrations. Younger mice were not similarly affected. These results suggest that MPTP-induced neurotoxicity is age-dependent and may be mediated by oxidative stress. (C) 1994 Wiley-Liss, Inc. C1 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. ARKANSAS STATE UNIV,DEPT SCI BIOL,STATE UNIV,AR 72467. NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. RP ALI, SF (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,HFT-132,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 40 TC 93 Z9 93 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1994 VL 18 IS 1 BP 27 EP 34 DI 10.1002/syn.890180105 PG 8 WC Neurosciences SC Neurosciences & Neurology GA PE144 UT WOS:A1994PE14400004 PM 7825121 ER PT J AU BENVENGA, S CAHNMANN, HJ RADER, D KINDT, M FACCHIANO, A ROBBINS, J AF BENVENGA, S CAHNMANN, HJ RADER, D KINDT, M FACCHIANO, A ROBBINS, J TI THYROID-HORMONE BINDING TO ISOLATED HUMAN APOLIPOPROTEINS A-II, C-I, C-II, AND C-III - HOMOLOGY IN THYROXINE-BINDING SITES SO THYROID LA English DT Article ID HIGH-DENSITY-LIPOPROTEINS; MULTIGENE FAMILY; GLOBULIN; LOCALIZATION; CHOLESTEROL; PREALBUMIN; PARTICLES; EVOLUTION; SEQUENCE AB Thyroid hormone binding to lipid-free apolipoprotein (ape) A-II, C-I, C-II, and C-III isolated from human plasma was investigated by photoaffinity labeling with [I-125]T-4 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both the monomeric and polymeric forms were specifically labeled. Inhibition by 10 mu M unlabeled L-T-4 was greater than or equal to 50%, suggesting affinity constants in the nM to mu M range; the least inhibition was seen with apoA-II. Unlabeled D-T-4 and reverse T-3 (rT(4)) gave the same inhibition as unlabeled L-T-4. Inhibitors of thyroid hormone binding to plasma proteins showed a different inhibitor potency with each apolipoprotein and a pattern different from that seen with T-4 binding globulin (TBG) and transthyretin (TTR). Also in contrast to TBG, where only unsaturated nonesterified fatty acids (NEFA) are effective inhibitors, both unsaturated and saturated NEFA as well as other lipids inhibited T-4 labeling. The flavonoid EMD 21388 was ineffective, confirming that it is a selective inhibitor of T-4 binding to TTR. T-4 binding to the apoCs was confirmed by the quenching of tryptophan fluorescence by unlabeled L-T-4. (ApoA-II was not studied since it lacks tryptophan.) Since the self-association of apolipoproteins involves interaction between amphipathic alpha-helices, and since the polymeric forms show specific T-4 binding properties as in the parent monomer, the T-4-binding domain appears to be outside the alpha-helical domain, as previously seen with apoA-I. The position of the T-4 binding sites of apoA-I, A-II, C-I, C-II, C-III, and E in the N-terminal, exon 3-coded regions (and in the exon 2-coded region of A-IV) is associated with amino acid homology, which is also shared with the T-4 binding domains of TBG, TTR, and serum albumin. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. UNIV MESSINA,SCH MED,INST CLIN MED 1,ENDOCRINOL SECT,I-98125 MESSINA,ITALY. NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. UNIV NAPLES,DEPT BIOCHEM & BIOPHYS,I-80135 NAPLES,ITALY. RI Facchiano, Antonio/K-5984-2016 OI Facchiano, Antonio/0000-0002-4243-2392 NR 28 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FAL PY 1994 VL 4 IS 3 BP 261 EP 267 DI 10.1089/thy.1994.4.261 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH851 UT WOS:A1994PH85100006 PM 7833661 ER PT J AU ROBBINS, J AF ROBBINS, J TI APPROACHES TO THE TREATMENT OF HIGH-RISK THYROID-CANCER SO THYROID LA English DT Article ID CARCINOMAS; METASTASES; RADIATION; MUTATIONS; ONCOGENE; GLAND RP ROBBINS, J (reprint author), NIDDKD,GENET & BIOCHEM BRANCH,BLDG 10,ROOM 8N315,BETHESDA,MD 20892, USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FAL PY 1994 VL 4 IS 3 BP 385 EP 387 DI 10.1089/thy.1994.4.385 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH851 UT WOS:A1994PH85100028 PM 7833681 ER PT J AU GHANAYEM, BI SANCHEZ, IM MATTHEWS, HB ELWELL, MR AF GHANAYEM, BI SANCHEZ, IM MATTHEWS, HB ELWELL, MR TI DEMONSTRATION OF A TEMPORAL RELATIONSHIP BETWEEN ETHYL ACRYLATE-INDUCED FORESTOMACH CELL-PROLIFERATION AND CARCINOGENICITY SO TOXICOLOGIC PATHOLOGY LA English DT Article DE MALE FISCHER-344 RATS; SUSTAINABILITY; REVERSIBILITY; CARCINOGENESIS AB Ethyl acrylate (EA) is a known forestomach carcinogen in both rats and mice. Recent work in this laboratory indicated that carcinogenic doses of EA administered by gavage for 13 wk resulted in a sustained increase in forestomach epithelial hyperplasia as long as exposure to EA continued. However, hyperplasia regressed and no forestomach neoplasms were seen after a 19-mo recovery period. Current studies were designed to further investigate the time required for sustained hyperplasia to lead to neoplasia as well as the organ specificity of EA-induced cell proliferation/hyperplasia vs carcinogenicity. EA was administered at 200 mg/kg (po) to male Fischer-344 rats, 5 days/wk. Squamous cell proliferation/hyperplasia was observed in the forestomach of all rats that received EA for 6 or 12 mo. Treatment of rats with EA for 12 mo followed by 2 mo of recovery resulted in the development of forestomach papillomas in 2 of 5 treated rats. Furthermore, animals treated for 12 mo and allowed 9 mo of recovery exhibited an increase in forestomach squamous cell carcinomas and papillomas at a combined incidence of 4 in 13. In contrast, animals treated with EA for 6 mo and allowed 2 or 15 mo of recovery exhibited a time-dependent regression of cell proliferation and did not develop forestomach neoplasms, No significant elevation in liver cell proliferation or neoplasia was seen at any time in any of the rats included in the present study, further confirming the organ specificity in the relationship between EA-induced cell proliferation and carcinogenicity. In conclusion, EA resulted in increased cell proliferation in the target organ of carcinogenicity (forestomach) but not in nontarget organs such as the lives. This work indicates that cell proliferation, sustained for a sufficient period of time, results in the development of neoplasia despite cessation of chemical administration. Furthermore, a temporal relationship exists between EA-induced epithelial cell proliferation and forestomach carcinogenicity. RP GHANAYEM, BI (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1994 VL 22 IS 5 BP 497 EP 509 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA PX206 UT WOS:A1994PX20600004 PM 7899778 ER PT J AU NII, A FUJIMOTO, R OKAZAKI, A NARITA, K MIKI, H AF NII, A FUJIMOTO, R OKAZAKI, A NARITA, K MIKI, H TI INTRAMEMBRANOUS AND ENDOCHONDRAL BONE CHANGES INDUCED BY A NEW BISPHOSPHONATE (YM175) IN THE BEAGLE DOG SO TOXICOLOGIC PATHOLOGY LA English DT Article DE ENDOCHONDRAL OSSIFICATION; INTRAMEMBRANOUS OSSIFICATION; PRIMARY SPONGIOSA; WOVEN BONE AB Oral treatment with a new bisphosphonate, YM175, for 13 wk resulted in increased bone tissue mass by both intramembranous and endochondral ossification processes in adult beagle dogs. Intramedullary bone formation due to intramembranous process was observed in dogs treated with a highly toxic dose of YM175. The newly formed woven bone trabeculae, showing immature to relatively mature figures, were present between the preexisting cancellous bone. The immature bone consisted of spindle-shaped mesenchymal cells with osteoid tissues. Many active osteoblasts surrounded the immature woven bone, while only few osteoclasts were seen on the surfaces of the new bone. Endochondral bone change was observed at the costochondral junction in ah YM175-treated groups. Accumulation of unresorbed mineralized cartilage with its covering of bone at this site resulted in an increase in length of the area of primary spongiosa. Although the endochondral bone change induced by YM175 was due to a bisphosphonate-induced inhibitory effect on bone resorption, the intramedullary bone formation is unique to YM175. RP NII, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FAIRVIEW 201,FREDERICK,MD 21702, USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1994 VL 22 IS 5 BP 536 EP 544 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA PX206 UT WOS:A1994PX20600009 PM 7899783 ER PT J AU BOORMAN, GA HAILEY, R GRUMBEIN, S CHOU, BJ HERBERT, RA GOEHL, T MELLICK, PW ROYCROFT, JH HASEMAN, JK SILLS, R AF BOORMAN, GA HAILEY, R GRUMBEIN, S CHOU, BJ HERBERT, RA GOEHL, T MELLICK, PW ROYCROFT, JH HASEMAN, JK SILLS, R TI TOXICOLOGY AND CARCINOGENESIS STUDIES OF OZONE AND OZONE 4-(N-NITROSOMETHYLAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN FISCHER-344/N RATS SO TOXICOLOGIC PATHOLOGY LA English DT Article DE HAZARD IDENTIFICATION; CHEMICAL CARCINOGENESIS; 2-YR STUDIES; AIR POLLUTION AB The purpose of this study was to evaluate the toxicity and potential carcinogenicity or cocarcinogenicity of ozone exposure in rats. Fischer-344/N (F-344/N) rats were exposed 6 hr/day, 5 days/wk, to 0, 0.12, 0.5, or 1.0 ppm ozone by inhalation for 2-yr and lifetime exposures. The cocarcinogenicity study included subcutaneous administration of 0, 0.1, or 1.0 mg/kg body weight of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and inhalation of 0 or 0.5 ppm ozone to male rats. NNK was administered by subcutaneous injections 3 times per week for the first 20 wk with ozone inhalation exposure. The ozone inhalation exposure was for 2 yr (104 wk), including the first 20 wk of NNK treatment and continuing for 84 wk after the last NNK injection. Ozone exposure caused a concentration-related increase in inflammation of the centriacinar region of the lung. There was also increased fibrosis and an extension of the bronchiolar epithelium in these centriacinar regions to involve the proximal alveoli. There was no increased incidence of neoplasms at any site, including the lung, that was associated with ozone exposure. Rats administered 1.0 mg/kg body weight NNK alone had an increased incidence of bronchiolar/alveolar neoplasms, but this effect was not enhanced by ozone exposure. Ozone exposure for 2 yr and lifetime was associated with site-specific toxic alterations in the nasal passage and lung similar to those previously described for short-term exposures. While there was significant attenuation of the pulmonary lesions as compared to short-term exposures, lesions persisted in the lifetime study and there was evidence of a mild progressive fibrosis. We conclude that under the conditions of these studies: (a) ozone exposure is not carcinogenic to either male or female F-344/N rats, (b) ozone does not enhance the incidence of pulmonary neoplasms in F-344/N rats exposed to a known pulmonary carcinogen (NNK), and (c) mild site-specific toxic lesions characteristic of ozone exposure persist in the nasal passage and lung throughout the lifetime of the rat with continued ozone exposure. RP BOORMAN, GA (reprint author), NIEHS,DIV INTRAMURAL RES,PATHOL BRANCH,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 18 Z9 19 U1 1 U2 2 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1994 VL 22 IS 5 BP 545 EP 554 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA PX206 UT WOS:A1994PX20600010 PM 7899784 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - RECOVERING DNA FROM AGAROSE GELS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note ID INEXPENSIVE MICRO-ELECTROELUTION; MOLECULAR-WEIGHT DNA; NUCLEIC-ACID; ELECTROPHORESIS; PURIFICATION; ACRYLAMIDE; ELUTION; EFFICIENT; FRAGMENTS AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. A commonly occurring theme on the net is the recovery of DNA, and this month's column discusses the pros and cons of various methods used to extract DNA fragments directly from agarose gels. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 17 TC 8 Z9 9 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD SEP PY 1994 VL 19 IS 9 BP 388 EP 389 DI 10.1016/0968-0004(94)90117-1 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PG895 UT WOS:A1994PG89500010 ER PT J AU LIBERSKI, PP RODGERSJOHNSON, P YANAGIHARA, R LEE, JW KRAMER, BS PICCARDO, P MORA, CA GIBBS, CJ GAJDUSEK, DC AF LIBERSKI, PP RODGERSJOHNSON, P YANAGIHARA, R LEE, JW KRAMER, BS PICCARDO, P MORA, CA GIBBS, CJ GAJDUSEK, DC TI ULTRASTRUCTURAL PATHOLOGY OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I ENCEPHALOMYELOPATHY IN A WHITE PATIENT WITH ADULT T-CELL LEUKEMIA/LYMPHOMA SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE I; MYCOSIS FUNGOIDES; RETROVIRUS; SPASTIC PARAPARESIS ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; MYELOPATHY; INFECTION; VISNA; ANTIBODIES; LYMPHOMA; DISEASE AB A white patient with human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma for 10 years died 4 months after the onset of spastic myelopathy. Ultrastructurally, the neuropathologic findings consisted of dystrophic neurites (spheroids) filled with neurofilaments or electron-dense bodies, intense astrocytic reaction with abundant formation of corpora amylacea, and multilamellar bodies. Demyelination and spongiform change were absent. Viruslike particles resembling HTLV-I were detected adjacent to brain endothelial cells. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NCI,NAVAL MED ONCOL BRANCH,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. NR 32 TC 5 Z9 5 U1 1 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD SEP-OCT PY 1994 VL 18 IS 5 BP 511 EP 518 PG 8 WC Microscopy; Pathology SC Microscopy; Pathology GA PG647 UT WOS:A1994PG64700008 PM 7810002 ER PT J AU REHM, S LIJINSKY, W AF REHM, S LIJINSKY, W TI SQUAMOUS METAPLASIA OF BRONCHIOLAR CELL-DERIVED ADENOCARCINOMA INDUCED BY N-NITROSOMETHYL-N-HEPTYLAMINE IN SYRIAN-HAMSTERS SO VETERINARY PATHOLOGY LA English DT Article DE CARCINOGENESIS; CLARA CELL; IMMUNOELECTRON MICROSCOPY; KERATIN; LUNG CANCER; SYRIAN HAMSTERS; TONOFILAMENTS ID LUNG-TUMORS; CLARA CELL; RESPIRATORY EPITHELIUM; EPIDERMOID METAPLASIA; ELECTRON-MICROSCOPY; CARCINOMA INSITU; LOCALIZED AREA; GOLDEN-HAMSTER; HISTOGENESIS; FEATURES AB Morphology and development of experimental bronchiolar lung tumors were studied in Syrian hamsters, using light and electron microscopic techniques. At the age of 9 weeks, 46 hamsters were each given one weekly gavage of 6.8 mg N-nitrosomethyl-n-heptylamine for 35 weeks, and hamsters were examined at intervals from 2 to 46 weeks. The present report describes the progression of adenocarcinomas of bronchiolar cell origin to adenosquamous and squamous cell carcinomas. Squamous metaplasia was commonly noted at the tumor periphery, i.e., zone of growth. In 20 hamsters, 22 adenosquamous and two squamous cell carcinomas (one a large cell carcinoma) were diagnosed by light microscopy. Overt keratinization was infrequent. Squamous cell metaplasia was not a feature of papillary neoplasms but was seen mainly with acinar structures. Ultrastructurally, squamous differentiation (metaplasia) appeared to develop along two different pathways. First, secretory cells were observed with large numbers of intermediate filaments and tonofilaments, with concurrent loss of organelles such as secretory granules and microvilli. Second, squamous metaplasia also appeared to develop from a progeny of tumor cells that failed to mature into secretory cells. Such cells were often present within the basal layer of secretory acini and resembled basal cells of the tracheobronchial tree. These observations were supported by increased expression of cytokeratins, as revealed by immunohistochemical procedures. Immunoelectron microscopic examination localized hamster Clara cell antigen in secretory granules of neoplastic Clara cells, in the cytoplasm between granules, and at the microvillous border. With the onset of squamous differentiation, Clara cell antigen was progressively lost from secretory cells and was only rarely seen in cells with tonofilaments. No labeling was present in squamous cells arising at the base of tumor acini. These results suggest that pulmonary squamous cell carcinomas may develop by direct squamous differentiation of secretory cells or may proceed from undifferentiated tumor cells. C1 NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,TUMOR PATHOL & PATHOGENESIS SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 58 TC 4 Z9 4 U1 0 U2 1 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 1994 VL 31 IS 5 BP 561 EP 571 PG 11 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA PE961 UT WOS:A1994PE96100008 PM 7801434 ER PT J AU FEDERSPIEL, MJ HUGHES, SH AF FEDERSPIEL, MJ HUGHES, SH TI EFFECTS OF THE GAG REGION ON GENOME STABILITY - AVIAN RETROVIRAL VECTORS THAT CONTAIN SEQUENCES FROM THE BRYAN STRAIN OF ROUS-SARCOMA VIRUS SO VIROLOGY LA English DT Article ID HIGH-TITER STRAIN; NUCLEOTIDE-SEQUENCE; GERM LINE; GENE; CHICKENS; INSERTION; ENV; SRC; DNA AB We have previously described replication-competent Schmidt Ruppin-A Rous sarcoma virus (RSV)-based retroviral vectors that can be used to deliver and express genes in avian cells. We have continued to modify the prototype vectors to develop a more versatile and efficient system. Substitution of the polymerase (pol) region from the Bryan high-titer RSV (BH-RSV) for the SR-A RSV pol region of these retroviral vectors causes these viruses to replicate more efficiently. We cloned the gag regions from two independent BH-RSV-transformed cell lines and tested whether substituting either of these gag regions would improve the replication and/or gene expression of the vectors. Chimeric vectors were constructed in which the gag region of the prototype vector (SR-A RSV) was replaced with the corresponding segment of BH-RSV gag in vectors that had either the original SR-A RSV pol or the BH-RSV pol region. All vectors contained the bacterial chloramphenicol acetyltransferase gene (CAT). The results indicate that different SR-A RSV and BH-RSV gag-pol chimeras can significantly affect the level of viral and CAT gene expression. The insertion of one of the BH-RSV gag regions, but not the other, gave rise to viruses with unstable genomes. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 26 TC 20 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP PY 1994 VL 203 IS 2 BP 211 EP 220 DI 10.1006/viro.1994.1478 PG 10 WC Virology SC Virology GA PB658 UT WOS:A1994PB65800002 PM 8053145 ER PT J AU YIN, SR PURCELL, RH EMERSON, SU AF YIN, SR PURCELL, RH EMERSON, SU TI A NEW CHINESE ISOLATE OF HEPATITIS-E VIRUS - COMPARISON WITH STRAINS RECOVERED FROM DIFFERENT GEOGRAPHICAL REGIONS SO VIRUS GENES LA English DT Article DE HEV GENOME; PCR; GENETIC HETEROGENEITY ID NON-B-HEPATITIS; TRANSMITTED NON-A; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; EPIDEMIC; RECOMBINATION; TRANSMISSION; EXPRESSION; PARTICLES; PAKISTAN AB The full-length cDNA of a new Chinese strain (KS2-87) of Hepatitis E virus (HEV) has been constructed and sequenced. The 5' noncoding region of KS2-87 is 26 nucleotides in length, which is one nucleotide shorter than that of HEV (B1) (Burma) and 23 nucleotides longer than that of HEV (Mexico). Comparison of the nucleotide and amino acid sequences of KS2-87 with all other published HEV sequences showed that KS2-87 was closer to two other Chinese strains (CHT-88, CHT-87) and SAR-55 (Pakistan) than to HEV (B1) and HEV (B2) (Burma) or HEV (Mexico). Comparisons of partial sequences of genes encoding a nonstructural and a structural protein revealed the existence of genetically related groups of HEV within geographical regions, whereas larger nucleotide differences were seen among isolates that were more geographically and epidemiologically distant. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. INST MICROBIOL & EPIDEMIOL,BEIJING,PEOPLES R CHINA. NR 28 TC 44 Z9 49 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD SEP PY 1994 VL 9 IS 1 BP 23 EP 32 DI 10.1007/BF01703432 PG 10 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA PP607 UT WOS:A1994PP60700003 PM 7871758 ER PT J AU SEGRAVES, MA GOLDBERG, ME AF SEGRAVES, MA GOLDBERG, ME TI EFFECT OF STIMULUS POSITION AND VELOCITY UPON THE MAINTENANCE OF SMOOTH-PURSUIT EYE VELOCITY SO VISION RESEARCH LA English DT Article DE OCULOMOTOR; SMOOTH PURSUIT; EYE MOVEMENTS; MACACA MULATTA ID MOVEMENTS; MOTION; CORTEX AB The relative contributions of retinal slip velocity and position errors to the generation of smooth pursuit eye movements were examined in three rhesus monkeys. Recognizing the unlikelihood of producing a pure retinal slip velocity or position error signal, these two stimulus parameters were combined under open-loop conditions. Both slip velocity and position error were used by the monkey to maintain an established eye velocity. Both parameters had the greatest effects upon eye velocity when they were in the same direction, enabling the monkey to maintain an established pursuit velocity. When slip velocity and position error were in the direction opposite to the initial pursuit, eye velocity reversed direction and moved very quickly towards zero. When the two parameters were in opposite directions, their effect upon eye velocity was minimized. C1 NORTHWESTERN UNIV,DEPT NEUROBIOL & PHYSIOL,EVANSTON,IL 60208. RP SEGRAVES, MA (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 15 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD SEP PY 1994 VL 34 IS 18 BP 2477 EP 2482 DI 10.1016/0042-6989(94)90291-7 PG 6 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA PB297 UT WOS:A1994PB29700013 PM 7975286 ER PT J AU PURCELL, RH MANNUCCI, PM GDOVIN, S GRINGERI, A COLOMBO, M MELE, A SCHINAIA, N CIAVARELLA, N EMERSON, SU AF PURCELL, RH MANNUCCI, PM GDOVIN, S GRINGERI, A COLOMBO, M MELE, A SCHINAIA, N CIAVARELLA, N EMERSON, SU TI VIROLOGY OF THE HEPATITIS-A EPIDEMIC IN ITALY SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT Symposium on Viral Safety of Plasma-Derived Replacement Factors for Hemophilia: How Safe is Safe, held Preceding the 35th Annual Meeting of the American-Society-of-Hematology CY DEC 03, 1993 CL ST LOUIS, MO SP AMER SOC HEMATOL ID VIRUS; PCR AB We studied the virologic aspects of a hepatitis A epidemic that occurred among hemophilia patients in Italy between 1989 and 1992. Twelve lots of factor VIII concentrate manufactured by the solvent-detergent chromatographic technique and suspected of contamination by the hepatitis A virus (HAV) were analyzed by a two-step, nested polymerase chain reaction (PCR) procedure. PCR was applied to 1-ml samples of factor VIII concentrate and 100-mu l serial serum samples available from 2 patients. Particular care was taken to rule out the possibility of false-positive results during analysis. Results demonstrated PCR amplification of the 3'-region of the VP3 gene in 5 of the 12 implicated lots of factor VIII and in the serial serum samples of both patients. PCR amplification also revealed that the gene sequences detected in patients' sera were identical to the sequences detected in the product they had received. In all, 3 VP3 sequences (found to be 96-99% identical) were amplified. Further characterization of the HAV found in the factor VIII concentrate and the patients' sera was attempted by PCR amplification of the VP1/2A region. Successful amplification of this region was achieved in the serum of only 1 patient and in the concentrate he received. This fourth amplified sequence was identical in both serum and factor VIII concentrate. Attempts to transmit hepatitis A from the contaminated lots to 3 chimpanzees resulted in no signs of infection after 10 months of observation. Based on the Italian experience, persons with severe hemophilia who receive large-pool concentrate are at potential risk for HAV infection and should be vaccinated against HAV or use an alternative to solvent-detergent-prepared concentrate. Since June 1992, no cases of HAV have been reported in Italian hemophiliacs, most of whom have been vaccinated. C1 NIAID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. MAGGIORE HOSP,IRCCS,ANGELO BIANCHI BONOMI HEMOPHILIA & THROMBOSIS CTR,MILAN,ITALY. MAGGIORE HOSP,IRCCS,INST INTERNAL MED,MILAN,ITALY. UNIV MILAN,MILAN,ITALY. IST SUPER SANITA,I-00161 ROME,ITALY. HEMOPHILIA & THROMBOSIS CTR,BARI,ITALY. RI Mannucci, Pier/C-3102-2014 NR 11 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD SEP PY 1994 VL 67 SU 4 BP 2 EP 7 PG 6 WC Hematology SC Hematology GA PK900 UT WOS:A1994PK90000002 PM 7831866 ER PT J AU MOSLEY, JW LEMON, SM FRICKE, W VERMYLEN, J PURCELL, RH MANNUCCI, PM HOROWITZ AF MOSLEY, JW LEMON, SM FRICKE, W VERMYLEN, J PURCELL, RH MANNUCCI, PM HOROWITZ TI VIRAL SAFETY OF PLASMA-DERIVED REPLACEMENT FACTORS FOR HEMOPHILIA - HOW SAFE IS SAFE - PROCEEDINGS OF A SYMPOSIUM HELD PRECEDING THE 35TH ANNUAL-MEETING AND EXPOSITION OF THE AMERICAN-SOCIETY-OF-HEMATOLOGY, DECEMBER 3, 1993, ST-LOUIS, MO - DISCUSSION SO VOX SANGUINIS LA English DT Discussion C1 NIAID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. MAGGIORE HOSP,IRCCS,INST INTERNAL MED,MILAN,ITALY. MAGGIORE HOSP,IRCCS,ANGELO BIANCHI BONOMI HEMOPHILIA & THROMBOSIS CTR,MILAN,ITALY. UNIV MILAN,MILAN,ITALY. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. US FDA,BETHESDA,MD 20014. CATHOLIC UNIV LEUVEN,CTR MOLEC & VASC BIOL,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,DIV BLEEDING & VASC DISORDERS,B-3000 LOUVAIN,BELGIUM. RP MOSLEY, JW (reprint author), CALIF STATE UNIV LOS ANGELES,SCH MED,DEPT MED,1840 N SOTO ST EDM 108,LOS ANGELES,CA 90032, USA. RI Mannucci, Pier/C-3102-2014 FU NHLBI NIH HHS [N01-HB-4-7002, N01-HB-4-7003, N01-HB-9-7074] NR 0 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD SEP PY 1994 VL 67 SU 4 BP 24 EP 26 PG 3 WC Hematology SC Hematology GA PK900 UT WOS:A1994PK90000007 PM 8091731 ER PT J AU HASAN, JAK CHOWDHURY, MAR SHAHABUDDIN, M HUQ, A LOOMIS, L COLWELL, RR AF HASAN, JAK CHOWDHURY, MAR SHAHABUDDIN, M HUQ, A LOOMIS, L COLWELL, RR TI CHOLERA-TOXIN GENE POLYMERASE CHAIN-REACTION FOR DETECTION OF NON-CULTURABLE VIBRIO-CHOLERAE O1 SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE CHOLERA TOXIN; NON-CULTURABLE; PCR; VIBRIO-CHOLERAE ID ENVIRONMENTAL-SAMPLES; VULNIFICUS; BACTERIA; CELLS AB Cholera enterotoxin is a major antigenic determinant for virulence of Vibrio cholerae O1 which can enter into a viable but non-culturable (N-C) state, not detectable by conventional culture methods, yet remain capable of producing enterotoxin and potentially pathogenic. PCR was applied in the current study to detect the cholera toxin (ctx) gene of N-C cells, thus eliminating the necessity of culture. Sets of oligonucleotide primers were designed, based on the ctxAB operon of V. cholerae O1, to detect the presence of the ctx gene. DNA from both culturable and N-C cells of V. cholerae O1 was amplified by PCR using sets of primers flanking 302-, 564- and 777-bp fragments of the ctx gene. The PCR method employed was capable of detecting the ctx gene in N-C V. cholerae in aquatic microcosms and in diarrheal stool samples from three patients who had distinct clinical symptoms of cholera but were culture-negative for V. cholerae O1 and non-O1 and enterotoxigenic Escherichia coli. Forty cycles of a two-step reaction (30 s each at 94 and 60-degrees-C) were optimal and more time efficient than a three-step PCR described previously. The procedure, from the point of heating microcosms or broth culture samples to observation on gels, requires < 4 h to complete. C1 NEW HORIZONS DIAGNOST CORP,COLUMBIA,MD. UNIV MARYLAND,DEPT MICROBIOL,COLLEGE PK,MD 20742. NIH,BETHESDA,MD 20892. NR 17 TC 10 Z9 10 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD SEP PY 1994 VL 10 IS 5 BP 568 EP 571 DI 10.1007/BF00367669 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA PG361 UT WOS:A1994PG36100020 PM 24421136 ER PT J AU JENG, JJ HUH, TL SONG, BJ AF JENG, JJ HUH, TL SONG, BJ TI PRODUCTION OF AN ENZYMATICALLY ACTIVE E1 COMPONENT OF HUMAN PYRUVATE-DEHYDROGENASE COMPLEX IN ESCHERICHIA-COLI - SUPPORTING ROLE OF E1-BETA SUBUNIT IN E1 ACTIVITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID E1-ALPHA SUBUNIT; LACTIC-ACIDOSIS; CDNA CLONES; RAT-LIVER; SEQUENCE; PURIFICATION; DEFICIENCY; PRECURSOR; CLONING AB A co-expression plasmid containing the coding sequence of both the human liver pyruvate dehydrogenase (PDH) E1 alpha and E1 beta subunits was constructed. Functionally active PDH E1 protein was produced when this co-expression plasmid was introduced into the host Escherichia coli cell, BL21 (DE3)/plysS. In contrast, the production of E1 alpha alone resulted in a catalytically inactive protein, suggesting an important role of the E1 beta subunit in constituting enzyme activity. The PDH E1 protein produced in E. coli was capable of being phosphorylated by PDH-specific kinase. This co-expression system will provide a useful tool for studying the biochemical properties of human PDH E1. (C) 1994 Academic Press, Inc. C1 KYUNGPOOK NATL UNIV,DEPT GENET ENGN,TAEGU 702701,SOUTH KOREA. RP JENG, JJ (reprint author), NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852, USA. NR 25 TC 10 Z9 10 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 AUG 30 PY 1994 VL 203 IS 1 BP 225 EP 230 DI 10.1006/bbrc.1994.2171 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300032 PM 8074659 ER PT J AU GOMEZ, DE LINDSAY, CK COTTAM, DW NASON, AM THORGEIRSSON, UP AF GOMEZ, DE LINDSAY, CK COTTAM, DW NASON, AM THORGEIRSSON, UP TI EXPRESSION AND CHARACTERIZATION OF HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES-1 IN A BACULOVIRUS-INSECT CELL SYSTEM SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COLLAGENASE INHIBITOR; FIBROBLAST COLLAGENASE; PURIFICATION; TUMOR; GLYCOSYLATION; PROTEINASES; INVITRO; VECTORS; TIMP-1; SERUM AB The baculovirus expression system was used to overexpress human tissue inhibitor of metalloproteinases-1 (TIMP-1). Approximately 5 mg of recombinant TIMP-1 was produced per 10(9) Sf9 insect cells infected with the recombinant baculovirus. The optimum time point for the production of biologically active rTIMP-1 was 20 hours postinfection. TIMP-1 activity was demonstrated by a soluble collagenase inhibition assay and reverse zymography. The baculovirus system has the advantage over previously described methods for generating human rTIMP-1 in that it generates large amounts of a fully glycosylated and active protein. (C) 1994 Academic Press, Inc. RP GOMEZ, DE (reprint author), NCI,DIV CANC ETIOL,BLDG 37,ROOM 2D-02,BETHESDA,MD 20892, USA. OI Gomez, Daniel E/0000-0002-8629-0787 NR 25 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 30 PY 1994 VL 203 IS 1 BP 237 EP 243 DI 10.1006/bbrc.1994.2173 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300034 PM 8074661 ER PT J AU JI, XD GALLORODRIGUEZ, C JACOBSON, KA AF JI, XD GALLORODRIGUEZ, C JACOBSON, KA TI A SELECTIVE AGONIST AFFINITY LABEL FOR A(3) ADENOSINE RECEPTORS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BINDING AB A newly synthesized, chemically reactive adenosine derivative, N-6-(3-isothiocyanatobenzyl)adenosine-5'-N-methyluronamide, was found to bind selectively to A(3) receptors. K-i values for this isothiocyanate derivative in competition binding at rat brain A(1), A(2a), and A(3) receptors were 145, 272 and 10.0 nM, respectively. A preincubation with this derivative resulted in irreversible inhibition of radioligand binding at rat A(3) receptors in membranes of transfected CHO cells or RBL-2H3 mast cells, but not at rat A(1) or A(2a) receptors. The loss of binding sites for 0.1 nM [(125)l]N-6-(4-aminobenzyl)adenosine-5'-N-methyluronamide, a high affinity A(3) receptor radioligand, in transfected CHO cell membranes was concentration-dependent with an IC50 of 50 n M. No change was observed in the K-d value of the remaining A(3) receptor sites. The inhibition was also insensitive to theophylline (1 mM), consistent with the pharmacology of rat A(3) receptors. Structurally similar adenosine analogues lacking the chemically reactive isothiocyanate group failed to irreversibly inhibit A(3)-binding. (C) 1994 Academic Press, Inc. C1 NIDDKD, BIOORGAN CHEM LAB, MOLEC RECOGNIT SECT, BETHESDA, MD 20892 USA. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 21 TC 15 Z9 15 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 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 30 PY 1994 VL 203 IS 1 BP 570 EP 576 DI 10.1006/bbrc.1994.2220 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300081 PM 8074705 ER PT J AU DYER, KD ROSENBERG, HF AF DYER, KD ROSENBERG, HF TI HSP70RY - FURTHER CHARACTERIZATION OF A NOVEL MEMBER OF THE HSP70 PROTEIN FAMILY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEAT-SHOCK PROTEINS; UNCOATING PROTEIN; CELL LINE; EXPRESSION; CLATHRIN; GENES; BINDING AB Hsp70RY was identified as a member of the hsp70 protein family on the basis of cDNA sequence homology (Fathallah, et. al. (1993) J. Immunol. 151, 810-813). We have shown that mRNA encoding hsp70RY is expressed in a variety of human cell lines and that mRNA expression remains unchanged in human promyelocytic HL-60 cells induced to differentiate with phorbol 12-myristate 13-acetate (PMA). We have also shown that the predicted amino acid sequence of hsp70RY diverges significantly from the other human hsp70 proteins and that it contains a unique glutamate-rich region near its carboxy-terminus. Finally, we have demonstrated the existence of a murine homolog of hsp70RY. (C) 1994 Academic Press, Inc. RP DYER, KD (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 6 Z9 7 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 AUG 30 PY 1994 VL 203 IS 1 BP 577 EP 581 DI 10.1006/bbrc.1994.2221 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300082 PM 8074706 ER PT J AU SETH, P AF SETH, P TI A SIMPLE AND EFFICIENT METHOD OF PROTEIN DELIVERY INTO CELLS USING ADENOVIRUS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MEMBRANE PERMEABILITY; PENTON BASE; KB-CELLS; TOXICITY; PH; ENHANCEMENT; INTERNALIZATION; PARTICLES; RELEASE AB Human adenovirus type 2 has been previously shown to increase the delivery of a variety of proteins into cells when Ad is co-internalized with the protein ligands. To increase the efficiency of adenoviral-mediated delivery of proteins, I have linked adenovirus, separately with two proteins, epidermal growth factor and an antibody against human transferrin receptor through disulfide and thioether linkages. Competition experiments indicate that the conjugates are taken up into the cells through adenovirus receptor. During the internalization of adenovirus-protein conjugates into KB cells, the conjugates were equally effective as the native adenovirus in disrupting endocytic vesicles and releasing their protein content into the cytosol. This implies the possible use of adenovirus to deliver a large number of protein molecules into the cells. (C) 1994 Academic Press, Inc. C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 26 TC 16 Z9 16 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 AUG 30 PY 1994 VL 203 IS 1 BP 582 EP 587 DI 10.1006/bbrc.1994.2222 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PD473 UT WOS:A1994PD47300083 PM 8074707 ER PT J AU LUBKOWSKI, J WLODAWER, A AMMON, HL COPELAND, TD SWAIN, AL AF LUBKOWSKI, J WLODAWER, A AMMON, HL COPELAND, TD SWAIN, AL TI STRUCTURAL CHARACTERIZATION OF PSEUDOMONAS 7A GLUTAMINASE-ASPARAGINASE SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI ASPARAGINASE; CRYSTAL-STRUCTURE; ACINETOBACTER; REFINEMENT; ENZYMES; SITE AB The amino acid sequence and a 2-Angstrom-resolution crystallographic structure of Pseudomonas 7A glutaminase-asparaginase (PGA) have been determined. PGA, which belongs to the family of tetrameric bacterial amidohydrolases, deamidates glutamine and asparagine. The amino acid sequence of PGA has a high degree of similarity to the sequences of other members of the family. PGA has the same fold as other bacterial amidohydrolases, with the exception of the position of a 20-residue loop that forms part of the active site. In the PGA structure presented here, the active site loop is observed clearly in only one monomer, in an open position, with a conformation different from that observed for other amidohydrolases. In the other three monomers the loop is disordered and cannot be traced. This phenomenon is probably a direct consequence of a very low occupancy of product(s) of the enzymatic reaction bound in the active sites of PGA in these crystals. The active sites are composed of a rigid part and the flexible loop. The rigid part consists of the residues directly involved in the catalytic reaction as well as residues that assist in orienting the substrate. Two residues that are important for activity reside on the flexible loop. We suggest that the flexible loops actively participate in the transport of substrate and product molecules through the amidohydrolase active sites and participate in orienting the substrate molecules properly in relation to the catalytic residues. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. FU NCI NIH HHS [N01-CO-74101] NR 31 TC 52 Z9 55 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 AUG 30 PY 1994 VL 33 IS 34 BP 10257 EP 10265 DI 10.1021/bi00200a005 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE328 UT WOS:A1994PE32800005 PM 8068664 ER PT J AU BURROUGHS, SE HORROCKS, WD REN, H KLEE, CB AF BURROUGHS, SE HORROCKS, WD REN, H KLEE, CB TI CHARACTERIZATION OF THE LANTHANIDE ION-BINDING PROPERTIES OF CALCINEURIN-B USING LASER-INDUCED LUMINESCENCE SPECTROSCOPY SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN PHOSPHATASE; TRANSFER DISTANCE MEASUREMENTS; CALCIUM-BINDING; ENERGY-TRANSFER; TROPONIN-C; EUROPIUM(III) LUMINESCENCE; EXCITATION SPECTROSCOPY; BRAIN CALCINEURIN; CYCLOSPORINE-A; CDNA CLONE AB Calcineurin (CaN) is a Ca2+/calmodulin-dependent protein phosphatase found in brain a nd other tissues. It is a heterodimer consisting of a catalytic subunit (CaN-A) and a Ca2+-binding regulatory subunit (CaN-B). The primary structure of CaN-B indicates that it, like calmodulin, is an EF-hand protein and binds four Ca2+ ions. Eu3+, due to its favorable spectroscopic and chemical properties, has been substituted for Ca2+ in CaN-B to determine the metal ion-binding properties of this ''calmodulin-like'' protein. Excitation of the F-7(0)-->D-5(0) transition of Eu3+ results in a spectrum similar to that of calmodulin, consisting of three peaks. Analysis of the spectral titration curves reveals four Eu3+-binding sites in CaN-B. The affinities vary: sites I and II have dissociation constants of 1.0 +/- 0.2 and 1.6 +/- 0.4 mu M, respectively; the values for sites III and IV are K-d = 140 +/- 20 and K-d = 20 +/- 10 nM, respectively. Binding of Tb3+ is slightly weaker. Tb3+ luminescence, sensitized by tyrosine, reveals that for lanthanides the highest affinity sites lie in the C-terminal domain. Energy transfer distance measurements between Eu3+ and Nd3+ in sites III and IV reveal a separation of 10.5 +/- 0.5 Angstrom, which suggests that these sites are arranged in a typical EF-hand pair. This information indicates that the overall structure of CaN-B is similar to the dumbbell-shaped proteins troponin-C and calmodulin, but is more like TnC in its metal-binding properties. C1 PENN STATE UNIV, DEPT CHEM, UNIVERSITY PK, PA 16802 USA. NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM23599] NR 67 TC 42 Z9 42 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 30 PY 1994 VL 33 IS 34 BP 10428 EP 10436 DI 10.1021/bi00200a026 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE328 UT WOS:A1994PE32800026 PM 8068681 ER PT J AU WHITESELL, L MIMNAUGH, EG DECOSTA, B MYERS, CE NECKERS, LM AF WHITESELL, L MIMNAUGH, EG DECOSTA, B MYERS, CE NECKERS, LM TI INHIBITION OF HEAT-SHOCK PROTEIN HSP90-PP60(V-SRC) HETEROPROTEIN COMPLEX-FORMATION BY BENZOQUINONE ANSAMYCINS - ESSENTIAL ROLE FOR STRESS PROTEINS IN ONCOGENIC TRANSFORMATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GELDANAMYCIN; TYROSINE KINASE ID ROUS-SARCOMA VIRUS; TYROSINE KINASE ONCOGENES; CELLULAR PROTEINS; HERBIMYCIN-A; MAMMALIAN-CELLS; HSP90; ASSOCIATION; PHOSPHORYLATION; MUTAGENESIS; PP60(V-SRC) AB The molecular mechanisms by which oncogenic tyrosine kinases induce cellular transformation are unclear. Herbimycin A, geldanamycin, and certain other benzoquinone ansamycins display an unusual capacity to revert tyrosine kinase-induced oncogenic transformation, As an approach to the study of v-src-mediated transformation, we examined ansamycin action in transformed cells and found that drug-induced reversion could be achieved without direct inhibition of src phosphorylating activity. To identify mechanisms other than kinase inhibition for drug-mediated reversion, we prepared a solid phase-immobilized geldanamycin derivative and affinity precipitated the molecular targets with which the drug interacted. In a range of cell lines, immobilized geldanamycin bound elements of a major class of heat shock protein (HSP90) in a stable and pharmacologically specific manner. Consistent with these binding data, we found that soluble geldanamycin and herbimycin A inhibited specifically the formation of a previously described src-HSP90 heteroprotein complex. A related benzoquinone ansamycin that failed to revert transformed cells did not inhibit the formation of this complex. These results demonstrate that HSP participation in multimolecular complex formation is required for src-mediated transformation and can provide a target for drug modulation. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NR 36 TC 1073 Z9 1101 U1 0 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 1994 VL 91 IS 18 BP 8324 EP 8328 DI 10.1073/pnas.91.18.8324 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800004 PM 8078881 ER PT J AU WANG, XM YEW, N PELOQUIN, JG VANDEWOUDE, GF BORISY, GG AF WANG, XM YEW, N PELOQUIN, JG VANDEWOUDE, GF BORISY, GG TI MOS ONCOGENE PRODUCT ASSOCIATES WITH KINETOCHORES IN MAMMALIAN SOMATIC-CELLS AND DISRUPTS MITOTIC PROGRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEIOTIC MATURATION; XENOPUS OOCYTES; MAP KINASE; CYTOPLASMIC DYNEIN; PROTO-ONCOGENE; MOUSE OOCYTES; METAPHASE; MITOSIS; MICROTUBULES; FIBROBLASTS AB The mos protooncogene has opposing effects on cell cycle progression. It is required for reinitiation of meiotic maturation and for meiotic progression through metaphase II, yet it is an active component of cytostatic factor. mos is a potent oncogene in fibroblasts, but high levels of expression are lethal. The lethality of mos gene expression in mammalian cells could be a consequence of a blockage induced by its cytostatic factor-related activity, which may appear at high dosage in mitotic cells. We have directly tested whether expression of the Mos protein can block mitosis in mammalian cells by microinjecting a fusion protein between Escherichia coli maltose-binding protein and Xenopus c-Mos into PtK1 epithelial cells and analyzing the cells by video time-lapse and immunofluorescence microscopy. Time-course analyses showed that Mos blocked mitosis by preventing progression to a normal metaphase. Chromosomes frequently failed to attain a bipolar orientation and were found near one pole. Injection of a kinase-deficient mutant Mos had no effect on mitosis, indicating that the blockage of mitotic progression required Mos kinase activity. Antitubulin immunostaining of cells blocked by Mos showed that microtubules were present but that spindle morphology was abnormal. Immunostaining for the Mos fusion protein showed that both wild-type and kinase mutant proteins Idealized at the kinetochores. Our results suggest that mitotic blockage by Mos may result from an action of the Mos kinase on the kinetochores, thus increasing chromosome instability and preventing normal congression. C1 UNIV WISCONSIN,MOLEC BIOL LAB,MADISON,WI 53706. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. OI Borisy, Gary/0000-0002-0266-8018 FU NIGMS NIH HHS [GM25062]; PHS HHS [N01-C0-74101] NR 32 TC 31 Z9 31 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 1994 VL 91 IS 18 BP 8329 EP 8333 DI 10.1073/pnas.91.18.8329 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800005 PM 8078882 ER PT J AU MIYAMURA, K KAJIGAYA, S MOMOEDA, M SMITHGILL, SJ YOUNG, NS AF MIYAMURA, K KAJIGAYA, S MOMOEDA, M SMITHGILL, SJ YOUNG, NS TI PARVOVIRUS PARTICLES AS PLATFORMS FOR PROTEIN PRESENTATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CAPSID; B19; LYSOZYME; GENE THERAPY; VACCINE ID EGG-WHITE LYSOZYME; B19 PARVOVIRUS; IMMUNE-RESPONSE; ANTIBODY; POLIOVIRUS; EXPRESSION; INFECTION; CELLS; RECOGNITION; RECEPTOR AB Empty capsids of the human pathogenic parvovirus B19 can be produced in a baculovirus system. B19 capsids are composed mainly of major capsid protein (VP2) and a small amount of minor capsid protein (VP1); VP1 is identical to VP2 but contains an additional 227-aa N-terminal region (''unique'' region). A portion of that region of VP1 is external to the capsid, and VP1 is not required for capsid formation. We substituted the unique region with a sequence encoding the 147 aa of hen egg white lysozyme (HEL) and constructed recombinant baculoviruses with variable amounts of retained VP1 sequence joined to the VP2 backbone. After cotransfection with VP2 baculovirus and expression in insect cells, capsids were purified by density sedimentation. Purified recombinant capsids contained HEL, External presentation of HEL was demonstrated by immunoprecipitation, ELISA, and immune electron microscopy using anti-lysozyme monoclonal antibodies or specific rabbit antisera. Empty particles showed enzymatic activity in a micrococcal cell wall digestion assay. Rabbits inoculated with capsids made antibodies to HEL. Intact heterologous protein can be incorporated in B19 particles and presented on the capsid surface, properties that may be useful in vaccine development, cell targeting, and gene therapy. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. NR 37 TC 32 Z9 33 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 1994 VL 91 IS 18 BP 8507 EP 8511 DI 10.1073/pnas.91.18.8507 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800041 PM 8078912 ER PT J AU RYU, S GARGES, S ADHYA, S AF RYU, S GARGES, S ADHYA, S TI AN ARCANE ROLE OF DNA IN TRANSCRIPTION ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CAMP RECEPTOR PROTEIN; COLI RNA-POLYMERASE; LAMBDA PL PROMOTER; ESCHERICHIA-COLI; ALPHA-SUBUNIT; BINDING; INVITRO; INITIATION; INVIVO; ACID AB The mechanism by which the cAMP receptor protein (CRP) activates transcription has been investigated using the lac promoter of Escherichia coli. For transcription activation, an interaction between DNA-bound CRP and RNA polymerase is not sufficient. CRP must bind to a site in the same DNA and close to the promoter. CRP action requires an intact spacer DNA to provide a rigid support in building a CRP-RNA polymerase protein bridge or to allow a conformational change in the DNA to be transmitted to the lac promoter using the protein bridge as a structural support. C1 NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 36 TC 25 Z9 25 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 1994 VL 91 IS 18 BP 8582 EP 8586 DI 10.1073/pnas.91.18.8582 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800056 PM 7811325 ER PT J AU YORK, DM WLODAWER, A PEDERSEN, LG DARDEN, TA AF YORK, DM WLODAWER, A PEDERSEN, LG DARDEN, TA TI ATOMIC-LEVEL ACCURACY IN SIMULATIONS OF LARGE PROTEIN CRYSTALS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; MOLECULAR-DYNAMICS; NUCLEIC-ACIDS; FORCE-FIELD; ENVIRONMENT; SYSTEMS; EWALD AB Proper treatment of long-range Coulombic forces presents a major obstacle to providing realistic molecular dynamics simulations of macromolecules. Traditional approximations made to lessen computational cost ultimately lead to unrealistic behavior, The particle mesh Ewald method accommodates long-range Coulombic forces accurately and efficiently by use of fast Fourier transform techniques. We report a 1-ns simulation of bovine pancreatic trypsin inhibitor in a crystal unit cell using the particle mesh Ewald methodology. We iind an rms backbone deviation from the x-ray structure (0.33 Angstrom) that is lower than that observed between bovine pancreatic trypsin inhibitor in different crystal forms and much lower than those of previous simulations. These results bridge the gap between structures obtained from molecular simulation and those from experiment. C1 NIEHS,RES TRIANGLE PK,NC 27709. DUKE UNIV,DEPT CHEM,DURHAM,NC 27706. MICROELECTR CTR N CAROLINA,N CAROLINA SUPERCOMP CTR,RES TRIANGLE PK,NC 27709. NCI,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU PHS HHS [N01-C0-74101] NR 27 TC 141 Z9 144 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 1994 VL 91 IS 18 BP 8715 EP 8718 DI 10.1073/pnas.91.18.8715 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800083 PM 7521533 ER PT J AU SHINDO, M DIBISCEGLIE, AM AKATSUKA, T FONG, TL SCAGLIONE, L DONETS, M HOOFNAGLE, JH FEINSTONE, SM AF SHINDO, M DIBISCEGLIE, AM AKATSUKA, T FONG, TL SCAGLIONE, L DONETS, M HOOFNAGLE, JH FEINSTONE, SM TI THE PHYSICAL STATE OF THE NEGATIVE STRAND OF HEPATITIS-C VIRUS-RNA IN SERUM OF PATIENTS WITH CHRONIC HEPATITIS-C SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-B HEPATITIS; NON-A; VIRAL-RNA; GENOME; ORGANIZATION; REPLICATION; SEQUENCES; INFECTION; REGION AB Negative strands of the hepatitis C virus (HCV) genome (a positive-stranded RNA virus) have been found in a nuclease-resistant form in the serum of patients with HCV infections. We determined whether a complete negative-strand copy is present in the serum, whether the negative strand is particle-associated, and finally, whether it is virion-associated and encapsidated like the positive (genomic) strand. Isopyknic sucrose and cesium chloride density ultracentrifugation followed by a strand-specific reverse transcription-polymerase chain reaction on the collected fractions was performed to determine whether both positive and negative strands were associated with similar particles. Both strands comigrated to approximately the same density (1.11-1.16 g/cm(3)) in sucrose. After treatment of the plasma with detergent (0.1% Nonidet P-40) to remove the viral envelope and centrifugation on cesium chloride gradients, the positive strands shifted to a density of 1.35 g/cm(3), and the negative strands were not detected. By using antibodies specific for the HCV core or envelope glycoproteins E1 or E2 coated onto the wells of a microtiter plate, it was possible to specifically bind HCV or viral cores to the solid phase. Pelleted virus particles were resuspended in either PBS or PBS with 0.1% Nonidet P-40 to expose the core. These pellets were then incubated in antibody-coated microtiter wells. RNA extracted from the bound and unbound fractions was tested for HCV RNA. The anti-core antibody was able to bind positive strands but not negative strands only in detergent-treated samples. In the nondetergent-treated pellets, the anti-E1 and -E2 bound the positive strand, but only anti-E1 bound the negative strands. These findings indicate that while both strands of HCV RNA can be detected in serum, the positive strand is encapsidated within the enveloped core, and the negative strand appears to be in a membrane particle associated with the viral envelope protein E1 but does not appear to be within the HCV core of circulating virions. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,HEPATITIS RES LAB,BETHESDA,MD 20892. NR 25 TC 31 Z9 31 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 30 PY 1994 VL 91 IS 18 BP 8719 EP 8723 DI 10.1073/pnas.91.18.8719 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE388 UT WOS:A1994PE38800084 PM 8078948 ER PT J AU ICHIKAWA, H DEGUCHI, T NAKAGO, T JACOBOWITZ, DM SUGIMOTO, T AF ICHIKAWA, H DEGUCHI, T NAKAGO, T JACOBOWITZ, DM SUGIMOTO, T TI PARVALBUMIN, CALRETININ AND CARBONIC-ANHYDRASE IN THE TRIGEMINAL AND SPINAL PRIMARY NEURONS OF THE RAT SO BRAIN RESEARCH LA English DT Note DE PARVALBUMIN; CARBONIC ANHYDRASE; CALRETININ; TRIGEMINAL GANGLION; DORSAL ROOT GANGLION; RAT ID DORSAL-ROOT GANGLIA; PRIMARY SENSORY NEURONS; CELL-SIZE ANALYSIS; TOOTH PULPS; IMMUNOHISTOCHEMICAL LOCALIZATION; TRANSGANGLIONIC TRANSPORT; HORSERADISH-PEROXIDASE; CENTRAL PROJECTIONS; MANDIBULAR MOLAR; NERVOUS-SYSTEM AB The cell-body size of parvalbumin-immunoreactive (-ir) primary neurons was measured in the trigeminal (TG) and lumber dorsal root ganglia (DRG). In the DRG, parvalbumin-ir was mostly detected in large cells (94% in the range of 600-2800 mu m(2)). Parvalbumin-ir TG cells were smaller than similar DRG cells and yet parvalbumin-ir TG cells of < 400 mu m(2) (2.86%) were rare. Trichrome stains for parvalbumin, calretinin (CR) and carbonic anhydrase (CA), and for parvalbumin, calcitonin gene-related peptide (CGRP) and CB were performed to estimate possible overlap of these substances. Virtually all parvalbumin-ir DRG cells contained CA activity while a small subpopulation (28.5%) of CR-ir DRG cells lacked CA activity. All the CR-ir DRG cells that exhibited CA were also ir for parvalbumin. 31.1% of parvalbumin-ir DRG cells exhibited CR-ir while 71.5% of CR-ir DRG cells showed parvalbumin-ir. All the CR-ir DRG cells of < 400 mu m(2) lacked CA activity and parvalbumin-ir while all those of > 800 mu m(2) exhibited both activities. similar to 30% of CR-ir DRG cells in the size range of 400-800 mu m(2) co-expressed CA. DRG cells co-expressing parvalbumin and CGRP were rare (similar to 1%). As was the case for the DRG, most of parvalbumin-ir TG cells exhibited CA activity (89.24%) and lacked CGRP-ir (96.6%). CR-ir TG cells were also subdivided into two groups; one with and the other without co-expression of CA. Unlike in the DRG, however, co-expression of parvalbumin and CR could never be detected in the TG. C1 OKAYAMA UNIV,SCH DENT,DEPT ORTHODONT,OKAYAMA 700,JAPAN. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP ICHIKAWA, H (reprint author), OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,2-5-1 SHIKATA CHO,OKAYAMA 700,JAPAN. NR 28 TC 64 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 29 PY 1994 VL 655 IS 1-2 BP 241 EP 245 DI 10.1016/0006-8993(94)91620-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PD247 UT WOS:A1994PD24700032 PM 7812779 ER PT J AU CADET, JL LADENHEIM, B BAUM, I CARLSON, E EPSTEIN, C AF CADET, JL LADENHEIM, B BAUM, I CARLSON, E EPSTEIN, C TI CUZN SUPEROXIDE-DISMUTASE (CUZNSOD) TRANSGENIC MICE SHOW RESISTANCE TO THE LETHAL EFFECTS OF METHYLENEDIOXYAMPHETAMINE (MDA) AND OF METHYLENEDIOXYMETHAMPHETAMINE (MDMA) SO BRAIN RESEARCH LA English DT Note DE TRANSGENIC MOUSE; SUPEROXIDE DISMUTASE; METHYLENEDIOXYAMPHETAMINE; METHYLENEDIOXYMETHAMPHETAMINE; LETHALITY; FREE RADICAL ID PARKINSONS-DISEASE; NEUROTOXICITY; BRAIN; NEURONS; GENDER; AGE AB We have used female and male transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene in order to assess the lethal effects of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA). In contrast to non-Tg mice, both heterozygous and homozygous SOD-Tg mice showed resistance to the lethal effects of both drugs. Females of both SOD-Tg and non-Tg strains were somewhat more resistant to the effects of these drugs in comparison to males. In general, homozygous animals show greater resistance to the effects of the two drugs. These results suggest that the acute lethal effects of amphetamine-substituted analogs might involve the intracellular overproduction of the superoxide radicals secondary to hypoxic injury. The gender differences suggest that there might be hormonal-free radical scavenger interactions that offer better protection to female mice. This might be related both to the lifespan of and to the lower prevalence of Parkinson's disease in women. Future studies will need to address these issues further. C1 UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. RP CADET, JL (reprint author), NIDA,ADDICT RES CTR,MOLEC NEUROPSYCHIAT SECT,POB 5180,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [AG-08938] NR 22 TC 76 Z9 77 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 29 PY 1994 VL 655 IS 1-2 BP 259 EP 262 DI 10.1016/0006-8993(94)91624-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA PD247 UT WOS:A1994PD24700036 PM 7812784 ER PT J AU CHRAPUSTA, SJ EGAN, MF MASSERANO, JM WYATT, RJ AF CHRAPUSTA, SJ EGAN, MF MASSERANO, JM WYATT, RJ TI DOPAMINE RELEASE IN THE RAT CEREBELLUM AND HIPPOCAMPUS - A TISSUE 3-METHOXYTYRAMINE STUDY SO BRAIN RESEARCH LA English DT Note DE 3-METHOXYTYRAMINE; DOPAMINE RELEASE; CEREBELLUM; HIPPOCAMPUS; ELECTROCONVULSIVE SHOCK; HALOPERIDOL; MASS FRAGMENTOGRAPHY ID INVIVO MICRODIALYSIS; ELECTROCONVULSIVE SHOCK; INTRACEREBRAL DIALYSIS; BRAIN; STRIATUM; METABOLITES; RECEPTORS; CORTEX; LOCALIZATION; HALOPERIDOL AB Multiple lines of evidence indicate dopamine is a neurotransmitter or neuromodulator in the cerebellum and hippocampus. In this study, we explored the utility of 3-methoxytyramine as an index of dopamine release in these regions. We found that: (1) cerebellar and hippocampal 3-methoxytyramine levels can be measured by combined gas chromatography-mass fragmentography with negative chemical ionization; (2) basal 3-methoxytyramine accumulation rates following monoamine oxidase inhibition, but not the steady-state tissue levels, are several times lower in these regions than in the frontal cortex; (3) accumulation of 3-methoxytyramine in the hippocampus and cerebellum can be enhanced following electroconvulsive shock, but not acute haloperidol (0.4 mg/kg) treatment. We conclude that 3-methoxytyramine accumulation may be a useful index of dopamine release in the cerebellum and hippocampus, but dopamine release is regulated differently in these regions than in the frontal cortex and striatum. RP CHRAPUSTA, SJ (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WAW BLDG,R 531,ML KING JR AVE,WASHINGTON,DC 20032, USA. NR 29 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 29 PY 1994 VL 655 IS 1-2 BP 271 EP 275 DI 10.1016/0006-8993(94)91627-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PD247 UT WOS:A1994PD24700039 PM 7812787 ER PT J AU DAVIS, CD GHOSHAL, A SCHUT, HAJ SNYDERWINE, EG AF DAVIS, CD GHOSHAL, A SCHUT, HAJ SNYDERWINE, EG TI METABOLIC-ACTIVATION OF HETEROCYCLIC AMINE FOOD MUTAGENS IN THE MAMMARY-GLAND OF LACTATING FISCHER-344 RATS SO CANCER LETTERS LA English DT Article DE 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE; 2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE; MUTAGENICITY; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE ID DNA-ADDUCTS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; BROILED SARDINE; COOKED FOODS; BEEF EXTRACT; CARCINOGENICITY; MEIQX; MICE; COMPOUND; MONKEYS AB We investigated the ability of the mammary gland to metabolically activate 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Although mammary gland microsomes had almost no capacity to metabolically activate the parent compounds, mammary gland cytosol was able to esterify the N-hydroxylamines. Acetyltransferase was the primary enzyme responsible for the phase II activation of the N-hydroxylamines. The level of acetyl CoA-stimulated binding when N-hydroxy PhIP served as the substrate was approximately 3- and 17-fold higher than when IQ and MeIQx served as substrates, respectively. N-Hydroxy-IQ and N-hydroxy PhIP can also be activated by tRNA synthetase and phosphatase, but not by sulfotransferase. However, the levels of proline- and ATP-enhanced DNA binding was approximately 30- and 60-fold lower than the acetyl CoA-enhanced DNA binding of lQ and PhIP, respectively. Differences observed in the phase II activation of the various heterocyclic amines in the mammary gland may explain why the mammary gland is a target organ for PhIP-induced carcinogenicity but not for IQ- or MeIQx-induced carcinogenicity in Fischer 344 rats. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. RP DAVIS, CD (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 29 PY 1994 VL 84 IS 1 BP 67 EP 73 DI 10.1016/0304-3835(94)90359-X PG 7 WC Oncology SC Oncology GA PF478 UT WOS:A1994PF47800009 PM 7915639 ER PT J AU YUSUF, S ZUCKER, D PEDUZZI, P FISHER, LD TAKARO, T KENNEDY, JW DAVIS, K KILLIP, T PASSAMANI, E NORRIS, R MORRIS, C MATHUR, V VARNAUSKAS, E CHALMERS, TC AF YUSUF, S ZUCKER, D PEDUZZI, P FISHER, LD TAKARO, T KENNEDY, JW DAVIS, K KILLIP, T PASSAMANI, E NORRIS, R MORRIS, C MATHUR, V VARNAUSKAS, E CHALMERS, TC TI EFFECT OF CORONARY-ARTERY BYPASS GRAFT-SURGERY ON SURVIVAL - OVERVIEW OF 10-YEAR RESULTS FROM RANDOMIZED TRIALS BY THE CORONARY-ARTERY BYPASS GRAFT-SURGERY TRIALISTS COLLABORATION SO LANCET LA English DT Article ID DISEASE AB We carried out a systematic overview using individual patient data from the seven randomised trials that have compared a strategy of initial coronary artery bypass graft (CABG) surgery with one of initial medical therapy to assess the effects on mortality in patients with stable coronary heart disease (stable angina not severe enough to necessitate surgery on grounds of symptoms alone, or myocardial infarction). 1324 patients were assigned CABG surgery and 1325 medical management between 1972 and 1984. The proportion of patients in the medical treatment group who had undergone CABG surgery was 25% at 5 years, 33% at 7 years, and 41% at 10 years: 93.7% of patients assigned to the surgery group underwent CABG surgery. The CABG group had significantly lower mortality than the medical treatment group at 5 years (10.2 vs 15.8%; odds ratio 0.61 [95% CI 0.48-0.77], p=0.0001), 7 years (15.8 vs 21.7%; 0.68 [0.56-0.83], p<0.001), and 10 years (26.4 vs 30.5%; 0.83 [0.70-0.98]; p=0.03). The risk reduction was greater in patients with left main artery disease than in those with disease in three vessels or one or two vessels (odds ratios at 5 years 0.32, 0.58, and 0.77, respectively). Although relative risk reductions in subgroups defined by other baseline characteristics were similar, the absolute benefits of CABG surgery were most pronounced in patients in the highest risk categories. This effect was most evident when several prognostically important clinical and angiographic risk factors were integrated to stratify patients by risk levels and the extension of survival at 10 years was examined (change in survival -1.1 [SE 3.1] months in low-risk group, 5.0 [4.2] months in moderate-risk group, and 8.8 [5.4] months in high-risk group; p for trend < 0.003). A strategy of initial CABG surgery is associated with lower mortality than one of medical management with delayed surgery if necessary, especially in high-risk and medium-risk patients with stable coronary heart disease. In low-risk patients, the limited data show a non-significant trend towards greater mortality with CABG. C1 NHLBI,BETHESDA,MD. MCMASTER UNIV,HAMILTON,ON,CANADA. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. VET AFFAIRS COOPERAT STUDIES PROGRAM,W HAVEN,CT. UNIV WASHINGTON,SEATTLE,WA. BETH ISRAEL HOSP,NEW YORK,NY. GREEN LANE HOSP,AUCKLAND,NEW ZEALAND. OREGON HLTH SCI UNIV,PORTLAND,OR. TEXAS HEART INST,HOUSTON,TX. GOTHENBURG UNIV,GOTHENBURG,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. TUFTS UNIV,BOSTON,MA. NR 20 TC 1175 Z9 1216 U1 4 U2 29 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 27 PY 1994 VL 344 IS 8922 BP 563 EP 570 DI 10.1016/S0140-6736(94)91963-1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PD424 UT WOS:A1994PD42400007 PM 7914958 ER PT J AU HILBERT, DM ANDERSON, AO HOLMES, KL RUDIKOFF, S AF HILBERT, DM ANDERSON, AO HOLMES, KL RUDIKOFF, S TI LONG-TERM LYMPHOID RECONSTITUTION OF SCID MICE SUGGESTS SELF-RENEWING B-CELL AND T-CELL POPULATIONS IN PERIPHERAL AND MUCOSAL TISSUES SO TRANSPLANTATION LA English DT Article ID MURINE PEYERS PATCH; GUT LAMINA PROPRIA; IGA PLASMA-CELLS; IMMUNOGLOBULIN PRODUCTION; HOMING RECEPTOR; LYMPHOCYTES; EXPRESSION; MOLECULE; GLYCOPROTEIN; SPECIFICITY AB Peyer's patch, peripheral lymph node, and mesenteric lymph node cells were transferred to immunodeficient SCID mice to assess the long-term (150-300 days) potential of these cells to repopulate the host's immune system. Results demonstrate that, irrespective of donor population, total serum Ig and isotype distribution appear normal within 4 weeks of reconstitution and remain at normal levels for up to one year following cell transfer. At the cellular level, each donor population reconstitutes splenic T and B cell compartments in a progressive and quantitatively indistinguishable manner. Immunohistological analyses of reconstituted mice indicate that, although some qualitative differences are evident, normal splenic composition and architecture are observed. In contrast, gut reconstitution varies significantly with donor population. Peyer's patch cells yield normal-appearing gut tissue with extensive infiltration of the lamina propria and intraepithelial compartments by T cells and IgA-secreting plasma cells. Peripheral lymph node cells give rise to T cells found almost exclusively in the lamina propria, while IgA secreting plasma cells are rarely detected. The course and extent of reconstitution further suggest that all donor populations contain long-lived T and B cells as well as self-renewing lymphocytes capable of extensive expansion. This latter observation has potentially important implications for both transplantation biology and gene therapy applications. C1 NIH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DEPT RESP & MUCOSAL IMMUNOL,FT DETRICK,MD 21701. NIAID,BIOL RESOURCES BRANCH,FLOW CYTOMETRY SECT,BETHESDA,MD 20892. RP HILBERT, DM (reprint author), NCI,GENET LAB,BLDG 37,RM 2B15,BETHESDA,MD 20892, USA. NR 39 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1994 VL 58 IS 4 BP 466 EP 475 DI 10.1097/00007890-199408270-00013 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PE120 UT WOS:A1994PE12000013 PM 8073516 ER PT J AU STEINBACH, PJ BROOKS, BR AF STEINBACH, PJ BROOKS, BR TI PROTEIN SIMULATION BELOW THE GLASS-TRANSITION TEMPERATURE - DEPENDENCE ON COOLING PROTOCOL SO CHEMICAL PHYSICS LETTERS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; NEUTRON-SCATTERING; MYOGLOBIN; HYDRATION; WATER AB To examine the discrepancy between experimentally observed and computer-simulated low-temperature protein motion, molecular dynamics (MD) simulations of hydrated and dry carboxymyoglobin (MbCO) were performed at 100 K following cooling at different rates and from different temperatures. Simulations were also performed at nine temperatures, from 100 to 300 K, after cooling both systems from 300 K at 0.2 K/ps. 'Slow' cooling resulted in low-energy structures that exhibited atomic fluctuation 25% closer to experimental levels than those employed in previous simulations. The additional electrostatic interactions accompanying hydration increased the need to cool slowly. Cooling hydrated MbCO from 400 K at 2 K/ps balanced realism and efficiency. RP STEINBACH, PJ (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BLDG 12A,ROOM 2041,BETHESDA,MD 20892, USA. NR 17 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD AUG 26 PY 1994 VL 226 IS 5-6 BP 447 EP 452 DI 10.1016/0009-2614(94)00754-3 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA PE005 UT WOS:A1994PE00500003 ER PT J AU DITTMER, J GEGONNE, A GITLIN, SD GHYSDAEL, J BRADY, JN AF DITTMER, J GEGONNE, A GITLIN, SD GHYSDAEL, J BRADY, JN TI REGULATION OF PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) GENE-EXPRESSION - SP1 BINDS THROUGH AN INVERTED CACCC MOTIF AND REGULATES PROMOTER ACTIVITY IN COOPERATION WITH ETS1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; LONG TERMINAL REPEAT; TRANSCRIPTIONAL ACTIVATION; RESPONSIVE ELEMENT; CONTROL REGION; PEPTIDE GENE; HTLV-I; C-ETS; GROWTH AB We have previously shown that mutations in the GGAA core motif of the Ets1 binding site, EBSI, or deletion of EBSI, reduced basal and Tax, transactivation of the PTHrP P2 promoter. Here we demonstrate that, in addition to EBSI, a CACCC-like motif located between -53 and -58 is required for full basal activity of this promoter in Jurkat T-cells. Site-specific mutations in the CACCC motif decreased promoter activity approximately 5-fold. In an effort to identify transcription factors that bind to the CACCC element, we found that purified human Sp1, as well as Sp1 in HeLa nuclear extract, can specifically bind to a DNA probe that corresponds to the PTRrP-specific sequence between -94 and -34. Gel shift competition studies and DNase I footprinting analyses revealed that Sp1 specifically interacts with the CACCC motif. In the presence of Ets1, the mobility of the Sp1-specific gel shift complex with the PTHrP DNA decreased. DNase I footprint analysis of this gel shift complex showed an extended footprint over both the Sp1 and the Ets1 binding site, demonstrating that Sp1 and Ets1 form a ternary complex with the PTRrP DNA. Cotransfection of an Ets1 and Sp1 expression vector into Drosophila Schneider cells demonstrated that Sp1 can functionally cooperate with Ets1 to transactivate the PTHrP promoter. We conclude from these data that Ets1 and Sp1 can cooperatively regulate PTHrP P2 promoter activity. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. CTR UNIV ORSAY,INST CURIE,BIOL SECT,F-91405 ORSAY,FRANCE. RI GHYSDAEL, Jacques/F-3377-2013; Dittmer, Juergen/G-1160-2011 NR 55 TC 64 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 AUG 26 PY 1994 VL 269 IS 34 BP 21428 EP 21434 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300009 PM 8063775 ER PT J AU SHEIKH, MS SHAO, ZM LI, XS DAWSON, M JETTEN, AM WU, SL CONLEY, BA GARCIA, M ROCHEFORT, H FONTANA, JA AF SHEIKH, MS SHAO, ZM LI, XS DAWSON, M JETTEN, AM WU, SL CONLEY, BA GARCIA, M ROCHEFORT, H FONTANA, JA TI RETINOID-RESISTANT ESTROGEN RECEPTOR-NEGATIVE HUMAN BREAST-CARCINOMA CELLS TRANSFECTED WITH RETINOIC ACID RECEPTOR-ALPHA ACQUIRE SENSITIVITY TO GROWTH-INHIBITION BY RETINOIDS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX GLA PROTEIN; X-RECEPTOR; CANCER CELLS; THYROID-HORMONE; GENE-EXPRESSION; GRANULOCYTIC DIFFERENTIATION; RAR-ALPHA; PROLIFERATION; IDENTIFICATION; SUPERFAMILY AB Retinoids mediate their actions via RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each class of these nuclear retinoid receptors is further subdivided into three species, namely alpha, beta, and gamma. Recent studies demonstrate that estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines and tumor samples exhibit significantly higher levels of RAR alpha than their ER-negative counterparts. ER-positive HBC cell lines are sensitive to, and ER-negative cell Lines are resistant to, growth inhibitory effects of retinoic acid (RA). We previously demonstrated that the expression of functional ERs in an established ER-negative cell line resulted in higher levels of RAR alpha and sensitivity to growth inhibition by RA. To further investigate the major role of RAR alpha in retinoid-mediated inhibition of growth, we transfected RAR alpha cDNA in two RA-resistant ER-negative HBC cell lines. Analyses of different clonal populations of RAR alpha transfectants from each cell line revealed growth inhibition by retinoids. Utilizing RAR- and RXR-class selective retinoids, we further demonstrated that only the RAR alpha-selective retinoids mediated the growth inhibition in these cells, while the RXR-selective retinoids were biologically inert. We thus provide evidence that the molecular mechanisms of retinoid inhibition of HBC proliferation predominantly involve RAR alpha. C1 UNIV MARYLAND,SCH MED,CTR CANC,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT MED,DIV ONCOL,BALTIMORE,MD 21201. UNIV MONTPELLIER 1,FAC MED,INSERM,U148,F-34090 MONTPELLIER,FRANCE. SRI INT,DIV LIFE SCI,MENLO PK,CA 94025. NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. OI Jetten, Anton/0000-0003-0954-4445; Fontana, Joseph/0000-0003-3829-3358 FU NCI NIH HHS [CA63335] NR 54 TC 108 Z9 109 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 26 PY 1994 VL 269 IS 34 BP 21440 EP 21447 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300011 PM 8063776 ER PT J AU KOHN, EC JACOBS, W KIM, YS ALESSANDRO, R STETLERSTEVENSON, WG LIOTTA, LA AF KOHN, EC JACOBS, W KIM, YS ALESSANDRO, R STETLERSTEVENSON, WG LIOTTA, LA TI CALCIUM INFLUX MODULATES EXPRESSION OF MATRIX METALLOPROTEINASE-2 (72-KDA TYPE-IV COLLAGENASE, GELATINASE-A) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; BASEMENT-MEMBRANE COLLAGEN; PROTEIN-KINASE-C; GENE-EXPRESSION; INTERSTITIAL COLLAGENASE; MAMMALIAN COLLAGENASES; INOSITOL PHOSPHATES; TISSUE INHIBITOR; PHORBOL ESTERS; MESSENGER-RNA AB Altered regulation of metalloproteinases may play a role in a variety of pathologic conditions including cancer. Previous studies have demonstrated transforming growth factor-beta(1) (TGF-beta(1))-mediated stimulation of expression and activation, and phorbol ester-mediated inhibition of matrix metalloproteinase (MMP)-2 (72-kDa type IV collagenase/gelatinase A), indicating a role for transmembrane signal transduction in MMP-2 regulation. We now describe a role for calcium mobilization in the regulation of MMP-2 expression. Receptor operated calcium influx has been shown to be inhibited by a novel synthetic inhibitor carboxy amido-triazole (CAI). Incubation of A2058 human melanoma, HT-1080 human fibrosarcoma, and OVCAR3 human ovarian cancer cells with CAI (0-10 mu M) resulted in a dose-dependent reduction in MMP-2 latent and activated species activity by zymogram analysis of conditioned medium. This reduction is not due to direct inhibition of the enzyme by CAI or CAI-induced MMP-2 degradation. Decreased quantity of secreted MMP-2 protein in CAI treated cells was shown by immunoblot and pulse-chase analysis of newly synthesized MMP-2. Cell coincubation with CAI (2 mu M) and TGF-beta(1) (5 ng/ml) caused a decrease in the overall amount of latent and activated MMP-2 by zymogram and immunoblot analysis and showed that CAI inhibited TGF-beta(1) stimulation of MMP-2 production at the level of RNA expression, This was confirmed by Northern analysis of A2058 cells treated with CAI (2 mu M) for 24 and 48 h and demonstrated a 55% reduction in message for MMP-2 and a 61% reduction in message for MMP-1, 54-kDa interstitial collagenase, Specificity for CAI action was demonstrated by equivalent MMP-2 inhibitory activity from analogs of CAI that retained the ability to inhibit calcium influx and by lack of inhibition by exposure to inactive CAI analogs that could not inhibit calcium influx. As an independent verification of specificity, a marked reduction in MMP-2 gelatinase activity by zymogram was shown after treatment of A2058 cells with SK&F 96365, an unrelated inhibitor of receptor-operated calcium influx. These results suggest a role for calcium-mediated signal transduction in the expression of metalloproteinases. RP KOHN, EC (reprint author), NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,SIGNAL TRANSDUCT & PREVENT UNIT,BLDG 10,RM 2A33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 46 TC 116 Z9 120 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 26 PY 1994 VL 269 IS 34 BP 21505 EP 21511 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300021 PM 8063786 ER PT J AU LEE, FJS STEVENS, LA HALL, LM MURTAGH, JJ KAO, YL MOSS, J VAUGHAN, M AF LEE, FJS STEVENS, LA HALL, LM MURTAGH, JJ KAO, YL MOSS, J VAUGHAN, M TI CHARACTERIZATION OF CLASS-II AND CLASS-III ADP-RIBOSYLATION FACTOR GENES AND PROTEINS IN DROSOPHILA-MELANOGASTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING PROTEINS; GLUTATHIONE-S-TRANSFERASE; CHOLERA-TOXIN; SACCHAROMYCES-CEREVISIAE; ADENYLATE-CYCLASE; ESCHERICHIA-COLI; MESSENGER-RNA; FACTORS ARFS; EXPRESSION; GTP AB ADP-ribosylation factors (ARFs) are ubiquitous similar to 20kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin and are involved in intracellular vesicular transport. Based on size, phylogenetic analysis, amino acid identity, and gene structure, mammalian ARFs fall into three classes (class I, ARF1, -2, and -3; class II, ARF4 and -5; class III, ARF6). A class I ARF had been identified in Drosophila melanogaster. To search for ARFs of other classes in Drosophila, polymerase chain reaction-based tech niques were used, resulting in cloning of Drosophila ARF (dARF) II and dARF III with deduced amino acid sequences similar to those of class II and class III mammalian ARFs, respectively. The three Drosophila ARF genes map to different chromosomes and the coding regions have different splicing sites. dARF II mRNA, like ARF I mRNA, is fairly uniformly distributed throughout adult flies, whereas dARF III mRNA is significantly more abundant in heads than in legs or bodies. Recombinant dARF II and dARF III have biochemical and immunological properties similar to those of human ARF5 (hARF5) and hARF6, respectively. These observations are consistent with the conclusion that the three classes of ARFs are present in non-mammalian as well as mammalian species. C1 SUNY BUFFALO,DEPT BIOCHEM PHARMACOL,AMHERST,NY 14260. RP LEE, FJS (reprint author), NHLBI,CELLULAR METAB LAB,RM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. OI LEE, FANG-JEN/0000-0002-2167-2426 FU NINDS NIH HHS [NS 16204] NR 41 TC 29 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 26 PY 1994 VL 269 IS 34 BP 21555 EP 21560 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300028 PM 8063793 ER PT J AU FRIGUET, B STADTMAN, ER SZWEDA, LI AF FRIGUET, B STADTMAN, ER SZWEDA, LI TI MODIFICATION OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE BY 4-HYDROXY-2-NONENAL - FORMATION OF CROSS-LINKED PROTEIN THAT INHIBITS THE MULTICATALYTIC PROTEASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; LIPOFUSCIN-LIKE SUBSTANCES; GLUTAMINE-SYNTHETASE; APOLIPOPROTEIN-B; OXIDATIVE STRESS; OXIDIZED LDL; MACROPHAGES; DEGRADATION; COMPLEX; LIVER AB Incubation of glucose-6-phosphate dehydrogenase (Glu-6-PDH) from Leuconostoc mesenteroides with the lipid peroxidation product 4-hydroxy-2-nonenal leads to the formation of cross-linked protein. This is accompanied by the appearance of protein-associated fluorescence with excitation and emission maxima of 340 and 415 nm, respectively, and with the disappearance of histidine and lysine residues. Cross-linked protein is less susceptible than native Glu-6-PDH to proteolysis by the multicatalytic protease, a multienzymic proteolytic complex involved in the intracellular degradation of damaged proteins. In addition, 4-hydroxy-2-nonenal-modified Glu-6-PDH inhibits the multicatalytic protease and can therefore prevent the efficient degradation of oxidized protein. These findings may have important implications for the accumulation of altered protein and fluorescent material in vivo, processes that are believed to be involved in age- and disease-related impairment of cellular function. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 39 TC 272 Z9 277 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 26 PY 1994 VL 269 IS 34 BP 21639 EP 21643 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK973 UT WOS:A1994PK97300041 PM 8063806 ER PT J AU WEISZ, A ANDRZEJEWSKI, D ITO, Y AF WEISZ, A ANDRZEJEWSKI, D ITO, Y TI PREPARATIVE SEPARATION OF COMPONENTS OF THE COLOR ADDITIVE D-AND-C RED NO-28 (PHLOXINE B) BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID STANDARDIZATION; PURIFICATION; PERFORMANCE; DERIVATIVES; STAINS; DYES AB A pH-zone-refining counter-current chromatographic method was developed for the preparative (multigram) separation and purification of components of the commercial color additive D&C Red No. 28 (phloxine B). The chromatography of 3 and 6 g of color additive yielded 1.07 and 4.06 g, respectively, of pure 2',4',5',7'-tetrabromo-4,5,6,7-tetrachlorofluorescein, the principal component of D&C Red No. 28. The importance of the quantity of retainer acid (trifluoroacetic acid) relative to the amount of salt in the color additive is discussed. C1 US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP WEISZ, A (reprint author), US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204, USA. NR 20 TC 28 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 26 PY 1994 VL 678 IS 1 BP 77 EP 84 DI 10.1016/0021-9673(94)87076-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PE486 UT WOS:A1994PE48600009 PM 7921192 ER PT J AU LEWIS, LK HARLOW, GR GREGGJOLLY, LA MOUNT, DW AF LEWIS, LK HARLOW, GR GREGGJOLLY, LA MOUNT, DW TI IDENTIFICATION OF HIGH-AFFINITY BINDING-SITES FOR LEXA WHICH DEFINE NEW DNA DAMAGE-INDUCIBLE GENES IN ESCHERICHIA-COLI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE LEXA; UMUDC; DNA REPAIR; SOS RESPONSE; DATABASE ID NUCLEOTIDE-SEQUENCE; REGULATORY PROTEINS; NEURAL NETWORKS; ANTISENSE RNA; RECA GENE; OOP RNA; REPRESSOR; PROMOTERS; K-12; MUTAGENESIS AB A multi-step screening procedure was devised to identify new operators for the LexA repressor in the sequenced portions of the genomes of Escherichia coli and its plasmids and bacteriophages. Sequence analysis methods were employed initially to distinguish true LexA operators from ''operator-like'' sequences stored within the GenBank and EMBL databases. The affinity of purified LexA protein for cloned DNA fragments containing several of the prospective new sites was then assessed using quantitative electrophoretic mobility shift assays and site-directed mutagenesis. Calculated binding affinities were compared directly with values determined for known and mutant LexA operators in concurrent experiments. Three E. coli chromosomal segments (near pyrC, hsdS and ntrla) and two bacteriophage sequences (near the P1 cre and lambda oop genes) bound LexA protein specifically. These sites and most others identified in the screening are located immediately upstream of known genes and/or large open reading frames. These results and additional transcription data demonstrate that several of the sequences define new DNA damage-inducible (din) genes and include the previously uncharacterized dinD locus. Furthermore, the search identified an SOS gene within the genome of P1 which encodes a protein that is homologous to UmuD', the RecA-promoted cleavage product of the umuD gene. The success of the combinatorial approach described here suggests that analogous searches for new regulatory sequences within the E. coli genome and the genomes of other organisms will also yield favorable results. C1 UNIV ARIZONA,DEPT MOLEC & CELLULAR BIOL,TUCSON,AZ 85721. RP LEWIS, LK (reprint author), NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA09213]; NIGMS NIH HHS [GM24496] NR 72 TC 135 Z9 139 U1 0 U2 6 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 26 PY 1994 VL 241 IS 4 BP 507 EP 523 DI 10.1006/jmbi.1994.1528 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD619 UT WOS:A1994PD61900001 PM 8057377 ER PT J AU FULLER, RW BOKESCH, HR GUSTAFSON, KR MCKEE, TC CARDELLINA, JH MCMAHON, JB CRAGG, GM SOEJARTO, DD BOYD, MR AF FULLER, RW BOKESCH, HR GUSTAFSON, KR MCKEE, TC CARDELLINA, JH MCMAHON, JB CRAGG, GM SOEJARTO, DD BOYD, MR TI HIV-INHIBITORY COUMARINS FROM LATEX OF THE TROPICAL RAIN-FOREST TREE CALOPHYLLUM-TEYSMANNII VAR INOPHYLLOIDE SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE AB In an effort to identify an adequate and sustainable natural source of the recently described anti-HIV drug development candidate calanolide A, we undertook chemical and biological studies of the latex exuded from trees of the genus Calophyllum. Although we found that calanolide A was not present in latex from the original source species, C. lanigerum var. austrocoriaceum, we did observe that a related coumarin, costatolide, was abundant in latex of C. teysmannii var. inophylloide. Costatolide is currently being evaluated as a possible alternative to calanolide A for drug development. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 9 TC 68 Z9 69 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 25 PY 1994 VL 4 IS 16 BP 1961 EP 1964 DI 10.1016/S0960-894X(01)80543-6 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PF115 UT WOS:A1994PF11500013 ER PT J AU XING, X GEDANKEN, A SHEYBANI, AH MCDIARMID, R AF XING, X GEDANKEN, A SHEYBANI, AH MCDIARMID, R TI THE 198-225-NM TRANSITION OF NORBORNADIENE SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID MULTI-PHOTON IONIZATION; SPECTROSCOPY; SPECTRA; BONDS AB An optical and two-photon resonant multiphoton ionization and photoacoustic spectroscopic investigation of the second transition region of norbornadiene was conducted on static and jet-cooled samples. Transitions to both the 3s Rydberg and the NV2 valence states were observed. The substructure of the 3s Rydberg <-- X transition was deduced to arise from fundamentals, overtones, and combinations of a(1), nu(4), nu(8), nu(10), and nu(12) and overtones and combinations of a(2), nu(18), and nu(20) vibrational modes. Displacements from the ground-state equilibrium geometry were determined for the a(1) modes. The 3s Rydberg state was shown to decay rapidly to the higher energy NV2 valence state via the nu(20) vibrational mode when energetically possible. The diffuse substructure of the NV2 transition was deduced to arise from nu(7), an ethylenic CH bending mode. Comparisons were made between results obtained here and those observed for similar molecules, observed for other states of this molecule, and calculated for these states of norbornadiene. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 25 TC 8 Z9 8 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD AUG 25 PY 1994 VL 98 IS 34 BP 8302 EP 8309 DI 10.1021/j100085a007 PG 8 WC Chemistry, Physical SC Chemistry GA PD464 UT WOS:A1994PD46400007 ER PT J AU SADEGHNASSERI, S STERN, LJ WILEY, DC GERMAIN, RN AF SADEGHNASSERI, S STERN, LJ WILEY, DC GERMAIN, RN TI MHC CLASS-II FUNCTION PRESERVED BY LOW-AFFINITY PEPTIDE INTERACTIONS PRECEDING STABLE BINDING SO NATURE LA English DT Article ID ANTIGENIC PEPTIDE; INVARIANT-CHAIN; HISTOCOMPATIBILITY MOLECULES; MICE LACKING; HLA-DR; EXPRESSION; COMPLEXES; HLA-DR1 AB MAJOR histocompatibility complex class II molecules and their peptide ligands show unusual interaction kinetics, with slow association and dissociation rates that yield an apparent equilibrium constant of similar to 10(-6)-10(-8) M (refs 1-5). However, there is evidence for a specific, rapidly formed, short-lived complex(6). The altered migration on SDS-polyacrylamide gel electrophoresis of class II molecules upon stable peptide binding(7-9) has led to the hypothesis that the two kinetically distinguishable types of class II-peptide complexes correspond to different structures. In accord with this model, we demonstrate here that insert cell-derived HLA-DR1 class II molecules show fast, almost stoichiometric occupancy with rapidly dissociating peptide while remaining sensitive to SDS-induced chain dissociation. The same DR1 molecules slowly and quantitatively form long-lived complexes resistant to SDS-induced denaturation. Surprisingly, low-affinity interaction with peptide protects class II from denaturation at physiological temperature, a finding that has implications for understanding the role of invariant chain in the intracellular behaviour of class II molecules. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. OI Sadegh-Nasseri, Scheherazade/0000-0002-8127-1720 NR 22 TC 127 Z9 127 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 AUG 25 PY 1994 VL 370 IS 6491 BP 647 EP 650 DI 10.1038/370647a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PD310 UT WOS:A1994PD31000049 PM 8065450 ER PT J AU HEISS, JD DOPPMAN, JL OLDFIELD, EH AF HEISS, JD DOPPMAN, JL OLDFIELD, EH TI RELIEF OF SPINAL-CORD COMPRESSION FROM VERTEBRAL HEMANGIOMA BY INTRALESIONAL INJECTION OF ABSOLUTE ETHANOL SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID PREOPERATIVE EMBOLIZATION; MALFORMATIONS; RADIOTHERAPY; RESECTION; BODY C1 NIH,WARREN B MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD. RP HEISS, JD (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10,RM 5D-37,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 55 Z9 57 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 25 PY 1994 VL 331 IS 8 BP 508 EP 511 DI 10.1056/NEJM199408253310804 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PD072 UT WOS:A1994PD07200004 PM 8041416 ER PT J AU ZULL, JE TAYLOR, RC MICHAELS, GS RUSHFORTH, NB AF ZULL, JE TAYLOR, RC MICHAELS, GS RUSHFORTH, NB TI NUCLEIC-ACID SEQUENCES CODING FOR INTERNAL ANTISENSE PEPTIDES - ARE THERE IMPLICATIONS FOR PROTEIN-FOLDING AND EVOLUTION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BINDING PEPTIDE; MESSENGER-RNA; GENETIC-CODE; RECEPTOR; COMPLEMENTARY; SIMILARITY; STRANDS; SENSE; DNA AB We have asked whether coding segments of nucleic acids generate amino acid sequences which have an antisense relationship to other amino acid sequences in the same chain (i.e. 'Internal Antisense'), and if so, could the internal antisense content be related to the structure of the encoded protein? Computer searches were conducted with the coding sequences for 132 proteins. The result for each search of a specific sequence was compared to the mean result obtained from 1000 randomly assembled nucleic acid chains whose length and base composition were identical to that of the native sequences. The study was conducted in all three reading frames. The normal reading frame (frame one) was found to be contain lower amounts of internal antisense than the randomly assembled chains, whereas the frame two results were much higher. The internal antisense content in frame three was not significantly different from that in the random chains. The amount of internal antisense in frames two and three was correlated with the GC content at the center position of the codons in that frame, but this correlation was absent in frame one. No correlation with chain length was found. Qualitatively similar results were obtained when the random model was limited to retain the same purine/pyrimidine ratio as the native chains at each position in the codons, but in this case the internal antisense in frame three was also significantly greater than the computer-generated sequences. The results suggest that the internal antisense content in the correct reading frame has a qualitatively different origin from that in the other two frames. The high amount in frames two and three is apparently an artifact resulting from the asymmetric distribution of G and C in the codons, while the low amount in frame one may suggest evolutionary selection against internal antisense. Thus, the results do not support a relationship between internal antisense and protein structure. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. GEORGE MASON UNIV,INST COMP SCI & INFORMAT,FAIRFAX,VA 22030. RP ZULL, JE (reprint author), CASE WESTERN RESERVE UNIV,DEPT BIOL,CLEVELAND,OH 44106, USA. NR 19 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 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 25 PY 1994 VL 22 IS 16 BP 3373 EP 3380 DI 10.1093/nar/22.16.3373 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF591 UT WOS:A1994PF59100014 PM 8078773 ER PT J AU JINADU, BA WELCH, G TALBOT, R CALDWELL, J JOHNSON, R BLUME, D EINSTEIN, H LARWOOD, T HARGRAVE, M JACKSON, RJ WERNER, SB DUFFEY, P RUTHERFORD, GW KIRKLAND, T PAPPAGIANIS, D SWATEK, F DIXON, DM AF JINADU, BA WELCH, G TALBOT, R CALDWELL, J JOHNSON, R BLUME, D EINSTEIN, H LARWOOD, T HARGRAVE, M JACKSON, RJ WERNER, SB DUFFEY, P RUTHERFORD, GW KIRKLAND, T PAPPAGIANIS, D SWATEK, F DIXON, DM TI UPDATE - COCCIDIOIDOMYCOSIS - CALIFORNIA, 1991-1993 (REPRINTED FROM MMWR, VOL 43, PG 421-423, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 CALIF DEPT HLTH SERV,SACRAMENTO,CA. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333. NIAID,BETHESDA,MD 20892. RP JINADU, BA (reprint author), KERN CTY HLTH DEPT,BAKERSFIELD,CA 93301, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 24 PY 1994 VL 272 IS 8 BP 585 EP 585 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PC398 UT WOS:A1994PC39800007 ER PT J AU PAHOR, M GURALNIK, JM SALIVE, ME CHRISCHILLES, EA BROWN, SL WALLACE, RB AF PAHOR, M GURALNIK, JM SALIVE, ME CHRISCHILLES, EA BROWN, SL WALLACE, RB TI PHYSICAL-ACTIVITY AND RISK OF SEVERE GASTROINTESTINAL HEMORRHAGE IN OLDER PERSONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANTI-INFLAMMATORY DRUGS; CORONARY HEART-DISEASE; COMMUNITY-BASED SAMPLE; BLEEDING PEPTIC-ULCER; DIVERTICULAR-DISEASE; EXERCISE; MEN; MORTALITY; ADULTS; FICSIT AB Objective.-To assess whether regular physical activity is associated with a decreased risk of severe gastrointestinal hemorrhage (GIH) in older persons. Design.-Cohort study with 3 years of follow-up. Setting.-Three communities of the Established Populations for Epidemiologic Studies of the Elderly. Participants.-A total of 8205 persons aged 68 years or older, yielding 22 277 person-years of follow-up. Measurements.-The occurrence of severe GIH was defined as either a hospital discharge diagnosis of gastrointestinal bleeding associated with blood transfusion or death during the hospital stay or a nonhospital death with mention of GIH on the death certificate. Physical activity was measured by self-reported frequency of walking, gardening, or doing vigorous physical activity. Those participants doing the activity three times per week or more were compared with the remaining participants. Adjusted relative risks (RRs) of GIH were controlled for age, gender, body mass index, blood pressure, chronic conditions, number of hospital admissions in the past year, and number and types of drugs taken. Results.-Severe GIH occurred in 241 participants (rate, 10.8 per 1000 person-years). After adjusting for potential confounding variables, the RRs and 95% confidence intervals (Cls) for severe GIH associated with walking, gardening, and vigorous physical activity were 0.6 (0.4 to 0.8), 0.8 (0.5 to 1.1), and 0.7 (0.4 to 1.2), respectively. The RR associated with a summary variable for the three activities was 0.7 (95% Cl, 0.5 to 0.9). These results were consistent after stratifying on health status and disability or by excluding those who were not mobile, ie, not able to walk half a mile or climb a flight of stairs. Conclusions.-Regular physical activity is associated with a decreased risk for severe GIH in older persons. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP PAHOR, M (reprint author), UNIV CATTOLICA SACRO CUORE,DEPT GERONTOL,LGO F VITO 1,I-00168 ROME,ITALY. NR 54 TC 31 Z9 31 U1 5 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 24 PY 1994 VL 272 IS 8 BP 595 EP 599 DI 10.1001/jama.272.8.595 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA PC398 UT WOS:A1994PC39800028 PM 8057514 ER PT J AU LONG, JB SKOLNICK, P AF LONG, JB SKOLNICK, P TI 1-AMINOCYCLOPROPANECARBOXYLIC ACID PROTECTS AGAINST DYNORPHIN A-INDUCED SPINAL-INJURY SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ACPC (1-AMINOCYCLOPROPANECARBOXYLIC ACID); NMDA (N-METHYL-D-ASPARTATE); NEURONAL INJURY; DYNORPHIN A; GLYCINE ID ASPARTATE RECEPTOR COMPLEX; GLYCINE MODULATORY SITE; RAT HINDLIMB PARALYSIS; CORD BLOOD-FLOW; NMDA RECEPTOR; NONOPIOID MECHANISMS; ANTAGONISTS; PEPTIDES; MOTOR; DYSFUNCTION AB Lumbar subarachnoid injection of dynorphin A causes an ischemia-induced neuronal degeneration and persistent hindlimb paralysis. The protective effects of a variety of competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists indicate that activation of the NMDA receptor complex is essential for dynorphin A-induced spinal cord injury. 1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity, partial agonist at strychnine-insensitive glycine receptors associated with the NMDA receptor complex. Pretreatment of rats with ACPC (100 and 200 mg/kg, i.p., 30 min prior to dynorphin A) significantly eliminated the persistent hindlimb motor deficits and neuropathological changes produced by 20 nmol of this peptide. The neuroprotective effects of ACPC (100 mg/kg, i.p.) were abolished by parenteral administration of glycine (800 mg/kg, 30 min prior to ACPC), consistent with other in vivo and in vitro studies indicating that the pharmacological actions of ACPC are effected through strychnine-insensitive glycine receptors. When given instead as six daily injections (200 mg/kg, i.p.) followed by an injection-free day, ACPC also significantly improved neurological recovery following dynorphin-A injection. These results support earlier indications that: (1) activation of the NMDA receptor complex plays a critical role in mediating dynorphin A-induced rat spinal cord injury; (2) ACPC provides an effective means of antagonizing excitotoxic phenomena; and (3) chronic administration of ACPC can elicit a persistent change in the NMDA receptor complex. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP LONG, JB (reprint author), WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT MED NEUROSCI,DIV NEUROPSYCHIAT,WASHINGTON,DC 20307, USA. NR 40 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 22 PY 1994 VL 261 IS 3 BP 295 EP 301 DI 10.1016/0014-2999(94)90120-1 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PD756 UT WOS:A1994PD75600009 PM 7813551 ER PT J AU RUBINEK, T MCMAHON, JB HIZI, A AF RUBINEK, T MCMAHON, JB HIZI, A TI INHIBITION OF REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND CHIMERIC ENZYMES OF HUMAN IMMUNODEFICIENCY VIRUSES TYPE-1 AND TYPE-2 BY 2 NOVEL NONNUCLEOSIDE INHIBITORS SO FEBS LETTERS LA English DT Article DE REVERSE TRANSCRIPTASE; HIV-1; HIV-2; UC-38; NITROPHENYL PHENYL SULFONE ID ESCHERICHIA-COLI; ANGSTROM RESOLUTION; HIV-1 REPLICATION; CRYSTAL-STRUCTURE; DERIVATIVES; POTENT; DNA AB We have studied the effects of two non-nucleoside reverse transcriptase inhibitors (NNRTI), nitrophenyl phenyl sulfone (NPPS) and a potent derivative of oxathiin carboxanilide (UC-38), on enzymatically active molecular chimeras composed of complementary segments of the reverse transcriptases (RTs) of human immunodeficiency virus type 1 (HIV-1) and -2 (HIV-2). The substances inhibit only the DNA polymerase activity of HIV-I RT with no effect on HIV-2 RT. The results suggest that there is a protein segment located between residues 158 and 190 that is critical for the inhibition by both compounds. However, there is probably a second segment that resides between residues 192 and 202, as in the case of NPPS, or residues 203 and 224, as in the case of UC-38, that is also crucial for the sensitivity of HIV-1 RT to both inhibitors. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HISTOL & CELL BIOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. FU NIAID NIH HHS [AI-31790] NR 25 TC 7 Z9 7 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 AUG 22 PY 1994 VL 350 IS 2-3 BP 299 EP 303 DI 10.1016/0014-5793(94)00793-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PD820 UT WOS:A1994PD82000034 PM 7520874 ER PT J AU RAHN, T RIDDERSTRALE, M TORNQVIST, H MANGANIELLO, V FREDRIKSON, G BELFRAGE, P DEGERMAN, E AF RAHN, T RIDDERSTRALE, M TORNQVIST, H MANGANIELLO, V FREDRIKSON, G BELFRAGE, P DEGERMAN, E TI ESSENTIAL ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE IN INSULIN-INDUCED ACTIVATION AND PHOSPHORYLATION OF THE CGMP-INHIBITED CAMP-PHOSPHODIESTERASE IN RAT ADIPOCYTES - STUDIES USING THE SELECTIVE INHIBITOR WORTMANNIN SO FEBS LETTERS LA English DT Article DE INSULIN; PHOSPHATIDYLINOSITOL 3-KINASE; INHIBITOR; ADIPOCYTE; LIPOLYSIS; CGMP-INHIBITED CAMP PHOSPHODIESTERASE ID DEPENDENT PROTEIN-KINASE; BOVINE BRAIN; FAT-CELLS; PURIFICATION; STIMULATION; LIPOLYSIS; RECEPTOR; IRS-1; 3'-KINASE; DOMAINS AB Incubation of rat adipocytes with wortmannin, a potent and selective phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, completely blocked the antilipolytic action of insulin (IC(50)approximate to 100 nM), the insulin-induced activation and phosphorylation of cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) as well as the activation of the insulin-stimulated cGI-PDE kinase (IC(50)approximate to 10-30 nM). No direct effects of the inhibitor on the insulin-stimulated cGI-PDE kinase, the cGI-PDE and the hormone-sensitive lipase were observed. These data suggest that activation of PI 3-kinase upstream of the insulin-stimulated cGI-PDE kinase in the antilipolytic insulin signalchain has an essential role for insulin-induced cGI-PDE activation/ phosphorylation and anti-lipolysis. C1 LUND UNIV,DEPT PAEDIAT,S-22100 LUND,SWEDEN. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. RP RAHN, T (reprint author), LUND UNIV,DEPT MED & PHYSIOL CHEM,POB 94,S-22100 LUND,SWEDEN. RI Ridderstrale, Martin/F-7678-2012 NR 39 TC 110 Z9 110 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 22 PY 1994 VL 350 IS 2-3 BP 314 EP 318 DI 10.1016/0014-5793(94)00797-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PD820 UT WOS:A1994PD82000037 PM 8070584 ER PT J AU ACKERMAN, MJ ANDERSON, R PERRY, M AF ACKERMAN, MJ ANDERSON, R PERRY, M TI THE TOXICOLOGY AND ENVIRONMENTAL-HEALTH INFORMATION PROGRAM OF THE NATIONAL-LIBRARY-OF-MEDICINE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL LIB MED,DIV SPECIALIZED INFORMAT SERV,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 1 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100919 ER PT J AU HUMPHREY, SM AF HUMPHREY, SM TI THE MEDINDEX KNOWLEDGE-BASED EXPERT-SYSTEM SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL LIB MED,CTR BIOMED COMMUN,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 5 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100945 ER PT J AU SHAFER, WS AF SHAFER, WS TI NIH-SUPPORTED RESEARCH - AN OPPORTUNITY FOR YOU SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIGMS,OFF PROGRAM ACT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 7 EP YCC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26902080 ER PT J AU WANG, AC GRZESIEK, S BAX, A AF WANG, AC GRZESIEK, S BAX, A TI ATTEMPTS AT CHARACTERIZING HYDROGEN-BONDS IN PROTEINS BY NMR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 7 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900620 ER PT J AU MARKS, C BREEN, JJ PALMER, C PRICE, E ANDERSON, D AF MARKS, C BREEN, JJ PALMER, C PRICE, E ANDERSON, D TI CHEMICAL SOCIETY OF WASHINGTON KIDS AND CHEMISTRY PROGRAM - CHEMISTS AND THEIR LOCAL SECTION IN-SERVICE TO THE COMMUNITY THROUGH CHEMICAL EDUCATION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SAIC INC,TYSONS CORNER,VA. US GEOL SURVEY,RESTON,VA 22092. US EPA,WASHINGTON,DC 20460. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 10 EP ENVR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101517 ER PT J AU MARQUEZ, VE LEE, J SHARMA, R LEWIN, NE BLUMBERG, PM MILNE, GWA WANG, S AF MARQUEZ, VE LEE, J SHARMA, R LEWIN, NE BLUMBERG, PM MILNE, GWA WANG, S TI THE DESIGN OF POTENT PK-C AGONISTS BASED ON A CONSTRAINED DIACYLGLYCEROL TEMPLATE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,DCT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENES & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 14 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102811 ER PT J AU ANDERSON, LM AF ANDERSON, LM TI RISK OF PERINATAL CARCINOGENESIS FROM WORKPLACE EXPOSURES - EVIDENCE FROM RODENT AND PRIMATE MODELS AND EPIDEMIOLOGY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 22 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100935 ER PT J AU JAIN, R AVRAMOVITCH, B COHEN, LA AF JAIN, R AVRAMOVITCH, B COHEN, LA TI SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF RING-HALOGENATED HISTIDINES AND HISTAMINES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 23 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102816 ER PT J AU GANSOW, OA WU, C BRECHBIEL, M AF GANSOW, OA WU, C BRECHBIEL, M TI DENDRIMER-BASED METAL-CHELATES - LINKAGE TO MONOCLONAL-ANTIBODIES AS ISOTOPE CARRIERS IN RADIOIMMUNOTHERAPY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,ROB,CHEM SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 24 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900024 ER PT J AU BUOLAMWINI, JK RAGHAVAN, K FESEN, M POMMIER, Y KOHN, KW WEINSTEIN, JN AF BUOLAMWINI, JK RAGHAVAN, K FESEN, M POMMIER, Y KOHN, KW WEINSTEIN, JN TI APPLICATION OF ELECTROTOPOLOGICAL STATE INDEXES TO QSAR STUDIES OF FLAVONES AS HIV-1 INTEGRASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 26 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102819 ER PT J AU LANG, L LEE, JT PAIK, CH ECKELMAN, WC AF LANG, L LEE, JT PAIK, CH ECKELMAN, WC TI SYNTHESIS OF [F-18] N-SUCCINIMIDYL 4-(FLUOROMETHYL)BENZOATE FROM N-SUCCINIMIDYL-4-[(4-NITROBENZENESULFONYL)OXYMETHYL]BENZOATE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 27 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900027 ER PT J AU JEONG, LS NICKLAUS, MC MARQUEZ, VE AF JEONG, LS NICKLAUS, MC MARQUEZ, VE TI SYNTHESIS AND ANTI-HIV ACTIVITY OF SUGAR-FLUORINATED 4'-THIO-2',3'-DIDEOXYNUCLEOSIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,DCT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 31 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102824 ER PT J AU HALLOCK, YF MANFREDI, KP BLUNT, JW CARDELLINA, JH BRINGMANN, G CLARDY, J FRANCOIS, G BOYD, MR AF HALLOCK, YF MANFREDI, KP BLUNT, JW CARDELLINA, JH BRINGMANN, G CLARDY, J FRANCOIS, G BOYD, MR TI NOVEL ANTIMALARIAL NAPHTHYLISOQUINOLINE ALKALOIDS FROM ANCISTROCLADUS-KORUPENSIS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 INST ORGAN CHEM,D-97074 WURZBURG,GERMANY. CORNELL UNIV,DEPT CHEM,ITHACA,NY 14853. NCI,FREDERICK CANC RES FACIL,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. INST TROP MED PRINCE LEOPOLD,B-2000 ANTWERP,BELGIUM. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 32 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102825 ER PT J AU PATTABIRAMAN, N GUSSIO, R TOPOL, I BURT, SK ERICKSON, JW AF PATTABIRAMAN, N GUSSIO, R TOPOL, I BURT, SK ERICKSON, JW TI AN ELECTRONIC CHARACTERIZATION OF A CONGENERIC SERIES OF NEVIRAPINE ANALOGS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 33 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102826 ER PT J AU GUSSIO, R PATTABIRAMAN, N KELLOGG, G BHAT, TN COLLINS, J BURT, SK ERICKSON, JW AF GUSSIO, R PATTABIRAMAN, N KELLOGG, G BHAT, TN COLLINS, J BURT, SK ERICKSON, JW TI HIV-1 REVERSE-TRANSCRIPTASE NEVIRAPINE BINDING-SITE MODEL - A 3D STRUCTURAL QSAR FOR LIGAND DESIGN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 34 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102827 ER PT J AU LAMBERT, C MEASE, RC LE, T SABET, H AVREN, LI MCAFEE, JG AF LAMBERT, C MEASE, RC LE, T SABET, H AVREN, LI MCAFEE, JG TI PREPARATION OF A HIGH SPECIFIC ACTIVITY I-125 LABELED STYRYL DYE FOR LEUKOCYTE MEMBRANE LABELING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 44 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900044 ER PT J AU BAKER, DC YAN, S COONEY, DA ZHANG, H AF BAKER, DC YAN, S COONEY, DA ZHANG, H TI SYNTHESIS AND BIOCHEMICAL-STUDIES ON THE 2,3-DIDEOXY-D-GLYCERO-PENTOFURANOSYL MOIETY OF 2',3'-DIDEOXY NUCLEOSIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 46 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100583 ER PT J AU BURKE, TR SMYTH, MS KOLE, HK AF BURKE, TR SMYTH, MS KOLE, HK TI PHOSPHONATE-CONTAINING PROTEIN-TYROSINE-PHOSPHATASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DTP,MED CHEM LAB,BALTIMORE,MD 21201. NCI,DCT,BALTIMORE,MD 21201. NIA,GRC,DIABET UNIT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 46 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102840 ER PT J AU JOHN, CS VILNER, BJ BOWEN, WD AF JOHN, CS VILNER, BJ BOWEN, WD TI THE DEVELOPMENT OF SIGMA-RECEPTOR SPECIFIC RADIOPHARMACEUTICALS FOR SPECT IMAGING OF HUMAN TUMORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20037. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 52 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900051 ER PT J AU KIESEWETTER, DO LEE, JT LANG, LX PARK, SG PAIK, CH ECKELMAN, WC AF KIESEWETTER, DO LEE, JT LANG, LX PARK, SG PAIK, CH ECKELMAN, WC TI SEARCH FOR A SUBTYPE-SELECTIVE MUSCARINIC LIGAND FOR RECEPTOR IMAGING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 54 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900053 ER PT J AU CHEN, XY SHEN, LX HINES, JV TINOCO, I CHAMORRO, M VARMUS, HE AF CHEN, XY SHEN, LX HINES, JV TINOCO, I CHAMORRO, M VARMUS, HE TI STRUCTURAL BASIS FOR PSEUDOKNOT-PROMOTED FRAMESHIFTING IN RETROVIRUSES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 60 EP BIOL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100497 ER PT J AU CACHAU, RE ERICKSON, JW AF CACHAU, RE ERICKSON, JW TI INTERMOLECULAR INTERACTION MAP REPRESENTATION IN DRUG DESIGN STUDIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYN CORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 61 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101368 ER PT J AU CACHAU, RE VILLAR, HO AF CACHAU, RE VILLAR, HO TI CALIBRATION OF THE ONSAGER CAVITY RADII ON GAUSSIAN-92 HF-SCRF CALCULATIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYN CORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. TERRAPIN TECHNOL INC,S SAN FRANCISCO,CA 94080. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 62 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101369 ER PT J AU CACHAU, RE ERICKSON, JW AF CACHAU, RE ERICKSON, JW TI FEEDBACK RESTRAINED MOLECULAR-DYNAMICS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYN CORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 63 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101370 ER PT J AU SHARMA, R WANG, S MILNE, GWA LEWIN, N BLUMBERG, PM MARQUEZ, VE AF SHARMA, R WANG, S MILNE, GWA LEWIN, N BLUMBERG, PM MARQUEZ, VE TI DISCOVERY OF N,N-BIS(2-HYDROXYETHYL)SULFONAMIDES AS NOVEL PROTEIN-KINASE-C (PK-C) AGONISTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,DCT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 71 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102865 ER PT J AU WANG, SM MILNE, GWA ZAHAREVITZ, DW SHARMA, R MARQUEZ, VE LEWIN, NE BLUMBERG, PM AF WANG, SM MILNE, GWA ZAHAREVITZ, DW SHARMA, R MARQUEZ, VE LEWIN, NE BLUMBERG, PM TI THE DISCOVERY OF NOVEL PK-C-AGONISTS THROUGH COMPUTER 3D-DATABASE PHARMACOPHORE SEARCH - MOLECULAR MODELING STUDIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK RES & DEV CTR,MED CHEM LAB,FREDERICK,MD 21701. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 72 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102866 ER PT J AU LEE, J MARQUEZ, VE BLUMBERG, PM LEWIN, NE AF LEE, J MARQUEZ, VE BLUMBERG, PM LEWIN, NE TI PROTEIN-KINASE-C AGONISTS - CONFORMATIONALLY CONSTRAINED DIACYLGLYCEROLS (DAG) ANALOGS BUILT ON A 2-DEOXYAPIOLACTONE TEMPLATE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,DCT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 73 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102867 ER PT J AU MARKOVIC, M FOWLER, BO HAILER, AW TUNG, MS AF MARKOVIC, M FOWLER, BO HAILER, AW TUNG, MS TI PREPARATION AND CHARACTERIZATION OF A CALCIUM HYDROXYAPATITE REFERENCE MATERIAL SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL INST STAND & TECHNOL,PRC ADAHF,GAITHERSBURG,MD 20899. NATL INST STAND & TECHNOL,NIDR,BRBRP,GAITHERSBURG,MD 20899. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 77 EP COLL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101136 ER PT J AU WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y AF WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y TI PREPARATIVE SEPARATION OF 4'-BROMO-4,5,6,7-TETRACHLOROFLUORESCEIN BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY WITH COMPUTERIZED SCANNING UV-VIS DETECTION AND CONTINUOUS PH MONITORING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 77 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100356 ER PT J AU SPENCE, C KREITMAN, RJ PASTAN, I BAILON, P AF SPENCE, C KREITMAN, RJ PASTAN, I BAILON, P TI AFFINITY PURIFICATION AND CHARACTERIZATION OF ANTI-TAC(FV)-C3-PE38KDEL - A HIGHLY POTENT CYTOTOXIC AGENT SPECIFIC TO CELLS BEARING IL-2 RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 HOFFMANN LA ROCHE INC,DEPT PROT BIOCHEM,NUTLEY,NJ 07110. NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 82 EP BIOL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100519 ER PT J AU HICKMAN, AB ENGELMAN, A PALMER, I WINGFIELD, P CRAIGIE, R DAVIES, DR AF HICKMAN, AB ENGELMAN, A PALMER, I WINGFIELD, P CRAIGIE, R DAVIES, DR TI BIOPHYSICAL CHARACTERIZATION OF TRUNCATED FORMS OF HIV-1 INTEGRASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 84 EP BIOL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100521 ER PT J AU ADACHI, YE PAVLAKIS, GN COPELAND, TD AF ADACHI, YE PAVLAKIS, GN COPELAND, TD TI IN-VIVO PHOSPHORYLATION SITES OF NUCLEAR-PROTEIN SET SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABI,BASIC RES PROGRAM,FREDERICK,MD 21702. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 87 EP BIOL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100524 ER PT J AU KOLECK, MP HO, DK CHMURNY, GN PAUKSTELIS, JV KLOSE, JR CONSTANTINESCU, A VATAKIS, AM MUSCHIK, GM MILLER, DA ROSS, JT POOLE, KK ROACH, JM LEBHERZ, WB SNADER, KM AF KOLECK, MP HO, DK CHMURNY, GN PAUKSTELIS, JV KLOSE, JR CONSTANTINESCU, A VATAKIS, AM MUSCHIK, GM MILLER, DA ROSS, JT POOLE, KK ROACH, JM LEBHERZ, WB SNADER, KM TI GELDANAMYCIN AND DERIVATIVES - PRODUCTION AND CHEMICAL STUDIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FERMENTAT PROD FACIL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DCT,DTP,NAT PROD BRANCH,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 89 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102883 ER PT J AU FULLER, RW CARDELLINA, JH JUREK, J SCHEUER, PJ ALVARADOLINDER, B MCGUIRE, M GRAY, GN STEINER, JR CLARDY, J MENEZ, E NEWMAN, DJ SNADER, KM BOYD, MR AF FULLER, RW CARDELLINA, JH JUREK, J SCHEUER, PJ ALVARADOLINDER, B MCGUIRE, M GRAY, GN STEINER, JR CLARDY, J MENEZ, E NEWMAN, DJ SNADER, KM BOYD, MR TI HALOMON ANALOGS - ADDITIONAL HALOGENTATED MONOTERPENES FROM PORTIERIA-HORNEMANNII WITH A NOVEL IN-VITRO ANTITUMOR RESPONSE PROFILE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYN CORP,FREDERICK,MD 21701. UNIV HAWAII,DEPT CHEM,HONOLULU,HI 96822. CORNELL UNIV,BAKER LAB,ITHACA,NY 14853. SMITHSONIAN INST,WASHINGTON,DC 20560. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 92 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102886 ER PT J AU ZHANG, HP FORD, H KELLEY, JA AF ZHANG, HP FORD, H KELLEY, JA TI ENHANCEMENT OF THE REVERSED-PHASE HPLC ANALYSIS OF 2'-FLUORO-2',3'-DIDEOXYADENOSINE, A NEW ANTI-AIDS DRUG, THROUGH FLUOROGENIC DERIVATIZATION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 96 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26100375 ER PT J AU MONSHIPOURI, M RUDOLPH, AS AF MONSHIPOURI, M RUDOLPH, AS TI A METHOD FOR FABRICATION OF MONODISPERSE HYDROGEL PARTICLES USING LIPOSOMES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NRL,WASHINGTON,DC 20375. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 108 EP POLY PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26901123 ER PT J AU KIRSCHENBAUM, LJ MISIK, V RIESZ, P AF KIRSCHENBAUM, LJ MISIK, V RIESZ, P TI A SONOCHEMICAL STUDY OF DIMETHYLFORMAMIDE-WATER MIXTURES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV RHODE ISL,DEPT CHEM,KINGSTON,RI 02881. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 153 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26900765 ER PT J AU CALDERON, SN KAYAKIRI, H RICE, KC AF CALDERON, SN KAYAKIRI, H RICE, KC TI DEVELOPMENT OF HIGHLY SELECTIVE NONPEPTIDIC DELTA-OPIOID RECEPTOR LIGANDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 159 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102952 ER PT J AU CONSTABLE, KP BLOUGH, BE MASCARELLA, SW ROTHMAN, RB CARROLL, FI AF CONSTABLE, KP BLOUGH, BE MASCARELLA, SW ROTHMAN, RB CARROLL, FI TI SYNTHESIS AND LIGAND-BINDING STUDIES AT PCP SITE-1 AND SITE-2 FOR SOME SUBSTITUTED BENZAZEPINES AND BENZAZOCINES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 169 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102962 ER PT J AU LEWIS, D MATECKA, D ROTHMAN, RB DERSCH, C PARTILLA, J PERT, A GLOWA, J WOJNICKI, F JACOBSON, AE RICE, KC AF LEWIS, D MATECKA, D ROTHMAN, RB DERSCH, C PARTILLA, J PERT, A GLOWA, J WOJNICKI, F JACOBSON, AE RICE, KC TI DISUBSTITUTED PIPERAZINES AS DOPAMINE REUPTAKE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,LMC,BETHESDA,MD 20892. NIDA,CPS,ADDICT RES CTR,BALTIMORE,MD 21224. NIMH,BPB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 173 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102966 ER PT J AU SHAH, JH NOWAK, G IZENWASSER, S WITKIN, JM NEWMAN, AH AF SHAH, JH NOWAK, G IZENWASSER, S WITKIN, JM NEWMAN, AH TI N-ALKYLAMINOBENZAZEPINE ANALOGS ARE HIGHLY SELECTIVE DOPAMINE-D(1) RECEPTOR ANTAGONISTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD 21224. UNIV MISSISSIPPI,MED CTR,DEPT PSYCHIAT & HUMAN BEHAV,JACKSON,MS 39216. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 174 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102967 ER PT J AU KEVERLINE, KI BOJA, JW KUHAR, MJ ABRAHAM, P LEWIN, AH CARROLL, FI AF KEVERLINE, KI BOJA, JW KUHAR, MJ ABRAHAM, P LEWIN, AH CARROLL, FI TI SYNTHESIS AND LIGAND-BINDING OF TROPANE ANALOGS - NEW SELECTIVE COMPOUNDS FOR THE SEROTONIN TRANSPORTER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 181 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102974 ER PT J AU KELKAR, SV IZENWASSER, S KATZ, JL KLEIN, CL TRUDELL, ML AF KELKAR, SV IZENWASSER, S KATZ, JL KLEIN, CL TRUDELL, ML TI SYNTHESIS AND BIOLOGICAL EVALUATION OF WIN-35,065-2 ANALOGS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL LAB,BALTIMORE,MD 21224. UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. XAVIER UNIV,DEPT CHEM,NEW ORLEANS,LA 70125. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 184 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102976 ER PT J AU HOULIHAN, WJ BOJA, JW PARRINO, VA KUHAR, MJ KOPAJTIC, TA AF HOULIHAN, WJ BOJA, JW PARRINO, VA KUHAR, MJ KOPAJTIC, TA TI HALOGENATED MAZINDOL ANALOGS AS POTENTIAL INHIBITORS OF THE COCAINE BINDING-SITE AT THE DOPAMINE TRANSPORTER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. SANDOZ INC,RES INST,E HANOVER,NJ 07936. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 185 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102977 ER PT J AU JOHN, CS VILNER, BJ BOWEN, WD AF JOHN, CS VILNER, BJ BOWEN, WD TI SYNTHESIS AND CHARACTERIZATION OF [I-125] N-(N-BENZYLPIPERIDIN-4-YL)-4-IODOBENZ AMIDE, A POTENTIAL HIGH-AFFINITY SIGMA-LIGAND FOR IMAGING BREAST-CANCER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 187 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102979 ER PT J AU ZHANG, Y BOWEN, WD WILLIAMS, W HE, XS DECOSTA, BR RICE, KC AF ZHANG, Y BOWEN, WD WILLIAMS, W HE, XS DECOSTA, BR RICE, KC TI SYNTHESIS AND RECEPTOR-BINDING OF SOME DIAMINE COMPOUNDS AS SIGMA-RECEPTOR LIGANDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,LMC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 188 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102980 ER PT J AU BERTHA, CM VILNER, BJ BOWEN, WD RICE, KC AF BERTHA, CM VILNER, BJ BOWEN, WD RICE, KC TI E-8-BENZYLIDENE 2-METHYL-5-PHENYLMORPHANS - POTENT SIGMA-RECEPTOR LIGANDS WITH SUBTYPE SELECTIVITY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 189 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102981 ER PT J AU ANANTHAN, S CLAYTON, SD WONG, G HARRIS, B SKOLNICK, P AF ANANTHAN, S CLAYTON, SD WONG, G HARRIS, B SKOLNICK, P TI GABA(A)/BENZODIAZEPINE RECEPTOR LIGANDS - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 3-SUBSTITUTED IMIDAZO[2,1-B]BENZOTHIAZOLE-2-CARBOXYLIC ESTERS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 193 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102985 ER PT J AU MATECKA, D WONG, G GU, ZQ SKOLNICK, P KORPI, E RICE, KC AF MATECKA, D WONG, G GU, ZQ SKOLNICK, P KORPI, E RICE, KC TI 8-AMINOALKYL-DERIVATIVES AND 8-ALKOXY-DERIVATIVES OF IMIDAZO[1,5-A][1,4]BENZODIAZEPINE T-BUTYL ESTERS AS NOVEL AND POTENT BENZODIAZEPINE RECEPTOR LIGANDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. ALKO BIOMED RES CTR,SF-00101 HELSINKI,FINLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 194 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102986 ER PT J AU SIDDIQI, SM PEARLSTEIN, RA SANDERS, LH JACOBSON, KA AF SIDDIQI, SM PEARLSTEIN, RA SANDERS, LH JACOBSON, KA TI QUANTITATIVE STRUCTURE-ACTIVITY STUDIES OF SELECTIVE A3 ADENOSINE AGONISTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 204 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102996 ER PT J AU VANRHEE, AM FISCHER, B JACOBSON, KA AF VANRHEE, AM FISCHER, B JACOBSON, KA TI MODELING THE P(2Y1) PURINOCEPTOR USING RHODOPSIN AS TEMPLATE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. BAR ILAN UNIV,DEPT CHEM,IL-52900 RAMAT GAN,ISRAEL. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 205 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102997 ER PT J AU KIM, HO JI, XD OLAH, ME STILES, GL JACOBSON, KA AF KIM, HO JI, XD OLAH, ME STILES, GL JACOBSON, KA TI STRUCTURE-ACTIVITY-RELATIONSHIPS OF ALKYLXANTHINE DERIVATIVES AT RAT A(3)-RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 206 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102998 ER PT J AU HUTCHINSON, KD SHAMIM, MT SHI, D DALY, JW AF HUTCHINSON, KD SHAMIM, MT SHI, D DALY, JW TI 1-METHYL-4-SUBSTITUTED-1H-PYRAZOLO[3,4-B]PYRIDINE-5-CARBOXYLIC ACID-DERIVATIVES - STRUCTURE-ACTIVITY-RELATIONSHIPS AT ADENOSINE RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 207 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102999 ER PT J AU ZHANG, Y KING, MM COHEN, LA AF ZHANG, Y KING, MM COHEN, LA TI STEREOPOPULATION CONTROL - APPLICATION TO PRODRUGS .2. RELATIONSHIP BETWEEN STRUCTURE AND REDUCTION POTENTIAL OF NITRO AROMATICS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 252 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26103045 ER PT J AU MILNE, GWA WANG, SM AF MILNE, GWA WANG, SM TI USE OF COMPUTERS IN TOXICOLOGY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 273 EP ENVR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26101780 ER PT J AU ANTONUCCI, JM AF ANTONUCCI, JM TI BIOACTIVE POLYMERIC DENTAL MATERIALS BASED ON AMORPHOUS CALCIUM-PHOSPHATE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIST,DIV POLYMERS,GAITHERSBURG,MD 20899. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 321 EP POLY PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26901335 ER PT J AU DOUGLAS, J HUBBARD, J ZHOU, HX AF DOUGLAS, J HUBBARD, J ZHOU, HX TI FRICTION COEFFICIENT OF POLYMER-CHAINS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL INST STAND & TECHNOL,DIV POLYMERS,GAITHERSBURG,MD 20899. NIDDKD,BETHESDA,MD 20892. NATL INST STAND & TECHNOL,DIV TECHNOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 347 EP PMSE PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26901871 ER PT J AU KHANGULOV, SV GLADYSHEV, VN DISMUKES, GC STADTMAN, TC AF KHANGULOV, SV GLADYSHEV, VN DISMUKES, GC STADTMAN, TC TI ACTIVE-CENTER OF MOLYBDENUM-SELENIUM CONTAINING OXOTRANSFERASES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. PRINCETON UNIV,DEPT CHEM,PRINCETON,NJ 08544. RI Dismukes, Gerard/I-4905-2012 OI Dismukes, Gerard/0000-0003-0155-0541 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 364 EP INOR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA261 UT WOS:A1994PA26102540 ER PT J AU KRUEGER, S ANDREWS, AP NOSSA, R AF KRUEGER, S ANDREWS, AP NOSSA, R TI SANS STUDIES OF AGAROSE GELS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 COLL WOOSTER,DEPT PHYS,WOOSTER,OH 44691. NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 21 PY 1994 VL 208 BP 381 EP PMSE PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA PA269 UT WOS:A1994PA26901905 ER PT J AU SMOLEN, P SHERMAN, A AF SMOLEN, P SHERMAN, A TI PHASE INDEPENDENT RESETTING IN RELAXATION AND BURSTING OSCILLATORS SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID PANCREATIC BETA-CELL; ELECTRICAL-ACTIVITY; CALCIUM CURRENTS; B-CELLS; MOUSE; ISLETS; MODEL; INACTIVATION; HETEROGENEITY; LANGERHANS AB Relaxation oscillators that depend on one slow variable, such as the Fitzhugh-Nagumo oscillator, reset in a phase-dependent manner. A complete oscillation can be divided into two parts, the ''plateau'' and ''trough'', and a prematurely induced plateau or trough is significantly shorter than normal. The class of square-wave bursting oscillators can be viewed as relaxation oscillators with rapid spikes during the plateau, and reset similarly when modeled with one slow variable. However, it has been reported that a physiological bursting oscillator, the membrane potential of the pancreatic beta-cell, resets in a phase-independent manner, such that a prematurely induced plateau/trough has normal length. A possible model for such an oscillator requires two slow variables, one to control the length of the plateau and the other the length of the trough. Here, we explore the geometric solution structure of two such models, which exhibit the desired resetting. One is a generalization of the Fitzhugh-Nagumo equations, and the other is a bursting oscillator using known beta-cell electrical currents with an additional hypothetical slow outward current. RP SMOLEN, P (reprint author), NIDDK,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 32 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD AUG 21 PY 1994 VL 169 IS 4 BP 339 EP 348 DI 10.1006/jtbi.1994.1156 PG 10 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA PG298 UT WOS:A1994PG29800004 PM 7967627 ER PT J AU MCCANCE, DR PETTITT, DJ BENNETT, PH KNOWLER, WC AF MCCANCE, DR PETTITT, DJ BENNETT, PH KNOWLER, WC TI TESTS FOR DIAGNOSING DIABETES-MELLITUS - REPLY SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ 85014. NIAMSD,PHOENIX,AZ 85014. RP MCCANCE, DR (reprint author), ROYAL VICTORIA HOSP,REG CTR ENDOCRINOL & DIABET,SIR GEORGE E CLARK METAB UNIT,BELFAST BT12 6BA,ANTRIM,NORTH IRELAND. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD AUG 20 PY 1994 VL 309 IS 6953 BP 538 EP 538 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PD308 UT WOS:A1994PD30800048 ER PT J AU RAYMOND, EG TAFARI, N TROENDLE, JF CLEMENS, JD AF RAYMOND, EG TAFARI, N TROENDLE, JF CLEMENS, JD TI DEVELOPMENT OF A PRACTICAL SCREENING TOOL TO IDENTIFY PRETERM, LOW-BIRTH-WEIGHT NEONATES IN ETHIOPIA SO LANCET LA English DT Article ID LOW-BIRTH-WEIGHT; INTRAUTERINE GROWTH-RETARDATION; DEVELOPING-COUNTRIES; MORTALITY; CIRCUMFERENCE; INFANTS; ARM; PREMATURITY; MORBIDITY; HEAD AB Preterm, low-birthweight (LBW) newborn infants are at high risk of neonatal mortality and morbidity and need early referral for special paediatric care. In developing countries, birthweight and gestational age often cannot be measured and a practical screening tool based on surrogate neonatal body measurements to identify high-risk infants would be very useful. We studied a consecutive series of 843 singleton infants born at a referral hospital in Addis Ababa, Ethiopia. Gestational age, birthweight, and four body measurements (chest, head, and mid-arm circumferences and length) were accurately recorded. We randomly divided the series into equal-sized training and validation groups. In the training group, we used a recursive partitioning technique to develop a simple predictive algorithm-infants were classified as high risk if head circumference was 31 cm or less or if chest circumference was 30 cm or less, and were classified as low risk otherwise. When tested in the validation group, this algorithm had sensitivity, specificity, and negative predictive value for prediction of preterm and LBW births above 90%. Thus, neonatal body measurements can be combined into a pragmatic, accurate screening tool suitable for clinical use in developing countries. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,ROCKVILLE,MD 20852. UNIV ADDIS ABABA,FAC MED,DEPT PEDIAT,ADDIS ABABA,ETHIOPIA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 20 PY 1994 VL 344 IS 8921 BP 524 EP 527 DI 10.1016/S0140-6736(94)91905-4 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PC535 UT WOS:A1994PC53500016 PM 7914620 ER PT J AU KONKEL, ME MARCONI, RT MEAD, DJ CIEPLAK, W AF KONKEL, ME MARCONI, RT MEAD, DJ CIEPLAK, W TI CLONING AND EXPRESSION OF THE HUP GENE ENCODING A HISTONE-LIKE PROTEIN OF CAMPYLOBACTER-JEJUNI SO GENE LA English DT Note DE RECOMBINANT DNA; DNA-BINDING PROTEIN; HU; PROMOTER; ENTERIC PATHOGEN ID ESCHERICHIA-COLI; DNA; HU-1 AB A Campylobacter jejuni gene, designated hup, that appears to encode a homolog of the histone-like DNA-binding protein, HU, has been cloned, sequenced and expressed in Escherichia coli. Immunoblotting and in vitro transcription/translation analyses revealed a 11-kDa protein that was produced by recombinant plasmids containing hup. The gene contains an open reading frame (ORF) sufficient to encode a protein of 98 amino acids (aa) with a calculated molecular mass of 10 267 Da and a predicted isoelectric point of 10.1. The deduced aa sequence of the protein, designated HCj, exhibits considerable sequence identity with members of the HU family of proteins from other eubacterial species. The transcription start point was identified by primer extension analysis and appropriately spaced promoter sequences were found which exhibit considerable similarity to E. coli and Bacillus promoters. Southern hybridization analyses indicate that C. jejuni has a single copy of hup. C1 NIAID, ROCKY MT LABS, VECTORS & PATHOGENS LAB, HAMILTON, MT 59840 USA. NR 20 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD AUG 19 PY 1994 VL 146 IS 1 BP 83 EP 86 DI 10.1016/0378-1119(94)90837-0 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA PD300 UT WOS:A1994PD30000012 PM 8063109 ER PT J AU LEE, FJS STEVENS, LA KAO, YL MOSS, J VAUGHAN, M AF LEE, FJS STEVENS, LA KAO, YL MOSS, J VAUGHAN, M TI CHARACTERIZATION OF A GLUCOSE-REPRESSIBLE ADP-RIBOSYLATION FACTOR-3 (ARF3) FROM SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING-PROTEINS; GLUTATHIONE-S-TRANSFERASE; CHOLERA-TOXIN; ESCHERICHIA-COLI; FACTOR-I; SELECTIVE AMPLIFICATION; ENDOPLASMIC-RETICULUM; GENE DISRUPTION; FACTOR-III; GOLGI AB ADP-ribosylation factors (ARFs) are highly conserved similar to 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin, and are believed to participate in vesicular transport in both exocytic and endocytic pathways. Based on size, phylogenetic analysis, amino acid sequence, and gene structure, mammalian ARFs fall into three classes (class I, ARFs 1, 2, 3; class II, ARFs 4, 5; class III, ARF6). Two ARF genes (gamma ARF1, gamma ARF2) are known in Saccharomyces cerevisiae and believed to participate in vesicular trafficking in the Golgi system; the double deletion mutant is not viable. A third yeast ARF (gamma ARF3) cDNA has been cloned by polymerase chain reaction-based procedures. It contains an open reading frame of 549 bases encoding a protein of 183 amino acids, with a deduced amino acid sequence more identical (60%) to that of the class III mammalian ARF than to those of the other two classes (52-56%). The gamma ARF3 protein, however, reacted poorly with antibodies against any of the three classes of mammalian ARFs. In the presence of GTP, recombinant gamma ARF3 protein stimulated cholera toxin catalyzed auto-ADP-ribosylation, gamma ARF3 gene transcription, similar to that of gamma ARF2, was repressed by glucose. As gamma ARF3 was not essential for cell viability and was not required for endoplasmic reticulum to Golgi protein transport, it may provide an opportunity to define an ARF function in another kind of vesicular trafficking. RP LEE, FJS (reprint author), NHLBI, CELLULAR METAB LAB, RM 5N-307, BLDG 10, BETHESDA, MD 20892 USA. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 50 TC 53 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 20931 EP 20937 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300021 PM 8063710 ER PT J AU CRESPO, P XU, NZ DANIOTTI, JL TROPPMAIR, J RAPP, UR GUTKIND, JS AF CRESPO, P XU, NZ DANIOTTI, JL TROPPMAIR, J RAPP, UR GUTKIND, JS TI SIGNALING THROUGH TRANSFORMING G-PROTEIN-COUPLED RECEPTORS IN NIH 3T3 CELLS INVOLVES C-RAF ACTIVATION - EVIDENCE FOR A PROTEIN KINASE-C-INDEPENDENT PATHWAY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; C-RAF-1 PROTEIN; EGF RECEPTOR; V-RAF; TRANSDUCTION; ONCOGENE; EXPRESSION; FAMILY; GENES AB We have studied the role of Raf-1 in mitogenesis and cellular transformation induced by G protein-coupled receptors in NIH 3T3 cells transfected with the human m1 muscarinic receptor. We have observed that in m1- expressing NIH 3T3 cells, the cholinergic agonist carbachol induces a dose- and time-dependent shift in the electrophoretic mobility of p72(Raf-1), equivalent to that observed when using phorbol esters or platelet-derived growth factor as stimulants. Phosphoamino acid analysis of slower mobility forms of p72(Raf-1) revealed both phosphoserine and phosphothreonine. Carbachol potently induced c-Raf activity as judged by its in vitro phosphorylating activity using MEK as a substrate. However, induction of Raf-1 kinase activity by carbachol occurred much earlier than changes in its electrophoretic mobility. Raf-1 kinase activation followed a kinetic similar to that exhibited by an epitope-tagged ERK2 protein when coexpressed in the same cells. Conventional protein kinase C (PKC) inactivation by means of sustained phorbol ester treatment or by a new nontoxic PKC-specific inhibitor, GF 109203X, abolished p72(Raf-1) mobility shift induced by carbachol or by phorbol esters. However, c-Raf and ERK2 enzymatic activity in response to carbachol was at least 50-80% PKC-independent. Furthermore, inhibition of PKC failed to affect DNA synthesis or focus formation induced by carbachol in cells expressing mi receptors. In contrast, cotransfection of NIH 3T3 cells with the Raf-1 dominant negative mutant Raf-301 (K375W) drastically decreased the transforming ability of mi receptors. Thus, our findings implicate Raf-1 activation in transformation by G protein-coupled receptors. In addition, our data suggest that activation of p72(Raf-1) and ERK2 by G protein-coupled receptors involves PKC-independent pathways. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALING UNIT,BETHESDA,MD 20892. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 61 TC 89 Z9 90 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 21103 EP 21109 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300045 PM 8063729 ER PT J AU BRESNICK, EH FELSENFELD, G AF BRESNICK, EH FELSENFELD, G TI THE LEUCINE-ZIPPER IS NECESSARY FOR STABILIZING A DIMER OF THE HELIX-LOOP-HELIX TRANSCRIPTION FACTOR USF BUT NOT FOR MAINTENANCE OF AN ELONGATED CONFORMATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOCUS-CONTROL REGION; MAJOR LATE PROMOTER; DOMINANT CONTROL REGION; DNA-BINDING; UPSTREAM ELEMENT; TRANSGENIC MICE; GLOBIN GENE; PROTEINS; DOMAIN; OLIGOMERIZATION AB The basic helix-loop-helix transcription factor USF43 binds to E box motifs on certain promoters and enhancers, as well as the beta-globin locus control region. We have used gel filtration chromatography, velocity centrifugation, and chemical cross-linking methods to investigate the stoichiometry and shape of USF43 in solution and when bound to DNA. USF43 has a very large Stokes' radius (44 Angstrom) and a high frictional ratio (1.64), consistent with an asymmetric elongated oligomer. Under a variety of conditions, the only detectible USF43 species in solution and bound to DNA is a dimer. The carboxyl-terminal leucine zipper is absolutely essential for a stable dimer but not for the elongated conformation. We used a protease footprinting assay to demonstrate that, when USF43 binds to DNA, a approximate to 15-kDa USF43 domain becomes resistant to cleavage with trypsin. This domain includes sequences that are not expected to interact with the DNA helix, suggesting that trypsin cleavage sites are masked by a conformational change. Our results show that the oligomerization state of USF43 does not change upon binding to DNA, and the helix-loop-helix oligomerization motif of USF43 is not itself sufficient to form a high affinity dimerization interface. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 39 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 21110 EP 21116 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300046 PM 8063730 ER PT J AU HOPE, JN CHEN, HC HEJTMANCIK, JF AF HOPE, JN CHEN, HC HEJTMANCIK, JF TI AGGREGATION OF BETA-A3-CRYSTALLIN IS INDEPENDENT OF THE SPECIFIC SEQUENCE OF THE DOMAIN CONNECTING PEPTIDE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTALLIN GENE FAMILY; MONOMERIC GAMMA-CRYSTALLIN; LENS BETA-CRYSTALLIN; X-RAY-ANALYSIS; EYE-LENS; EVOLUTIONARY RELATIONSHIPS; 3-DIMENSIONAL STRUCTURE; NUCLEOTIDE-SEQUENCE; CIRCULAR-DICHROISM; BP CHAIN AB The beta- and gamma-crystallins are structural proteins whose high concentration and close packing are important in maintaining transparency of the eye lens. The beta gamma-crystallin superfamily includes proteins with similar core structures consisting of two compact domains linked by a short connecting peptide. In gamma-crystallins, the connecting peptide folds back on itself, allowing the amino and carboxyl domains to participate in close interactions. The beta-crystallin connecting peptide is extended so that dimerization of two beta-crystallin monomers is required for similar interdomain interactions. In order to examine the role of the sequence of the connecting peptide in determining the extended beta-crystallin conformation and hence their association into dimers, we have exchanged the 10 residues of the beta A3-crystallin connecting peptide with the 9-residue connecting peptide sequence of mouse gamma B-crystallin by site-directed mutagenesis. Unaltered and modified recombinant beta A3-crystallins were expressed in a baculovirus system and purified by sequential anion exchange chromatography and gel filtration. Integrity of the recombinant crystallins was confirmed by NH2-terminal sequence analysis, immunoblots, and CD spectrometry. Reconstitution of the mutant recombinant protein with crystallins from mouse lens soluble extract resulted in aggregates of identical size distribution as normal beta A3-crystallin. We conclude that the sequence of the connecting peptide is not critical for the association of beta A3-crystallin into dimers and higher order aggregates as had been postulated. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 32 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 21141 EP 21145 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300051 PM 8063735 ER PT J AU XIAO, S ROSE, DW SASAOKA, T MAEGAWA, H BURKE, TR ROLLER, PP SHOELSON, SE OLEFSKY, JM AF XIAO, S ROSE, DW SASAOKA, T MAEGAWA, H BURKE, TR ROLLER, PP SHOELSON, SE OLEFSKY, JM TI SYP (SH-PTP2) IS A POSITIVE MEDIATOR OF GROWTH FACTOR-STIMULATED MITOGENIC SIGNAL-TRANSDUCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; INSULIN-RECEPTOR; KINASE; SH2; PHOSPHORYLATION; CORKSCREW; BINDING; ASSOCIATION; ACTIVATION AB Syp (SH-PTP2) was recently identified as a phosphotyrosine phosphatase containing two SH2 domains within its primary structure. In response to appropriate growth factor stimulation, Syp becomes phosphorylated on tyrosine residues and associates with insulin receptor substrate 1 (IRS-1) and/or the corresponding growth factor receptor via its SH2 domains, leading to increased Syp activity. To assess the importance of Syp in mitogenic signaling, we microinjected mammalian fibroblasts with several reagents designed to interfere with Syp SH2/phosphotyrosine interaction in vivo. Insulin-, insulin-like growth factor-1-, and epidermal growth factor-stimulated DNA synthesis, indicated by bromodeoxyuridine (BrdUrd) incorporation, was dramatically decreased following microinjection of a Syp antibody (Ab) (65-85%) or a Syp GST-SH2 fusion protein (similar to 90%) in comparison with cells microinjected with control IgG or glutathione S-transferase (GST), respectively. In addition, microinjection of an IRS-1-derived phosphonopeptide, which inhibits in vitro binding of Syp-SH2 to IRS-1 with an ED(50) value of similar to 23 mu M, also decreased BrdUrd incorporation in vivo by approximately 50-75%. Microinjection of the Syp Ab, Syp GST-SH2 fusion protein, or the phosphonopeptide had no effect on serum-stimulated BrdUrd incorporation. In conclusion, disruption of Syp function in living cells inhibited cell cycle progression in response to growth factor stimulation, indicating that Syp is a critical positive regulator of mitogenic signal transduction. C1 UNIV CALIF SAN DIEGO,DEPT MED,DIV ENDOCRINOL & METAB,LA JOLLA,CA 92093. VET ADM MED CTR,MED RES SERV,SAN DIEGO,CA 92126. SHIGA UNIV MED SCI,DEPT MED 3,OTSU,SHIGA 52021,JAPAN. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK33651] NR 31 TC 253 Z9 253 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 21244 EP 21248 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300065 PM 8063747 ER PT J AU MERTZ, PM DEWITT, DL STETLERSTEVENSON, WG WAHL, LM AF MERTZ, PM DEWITT, DL STETLERSTEVENSON, WG WAHL, LM TI INTERLEUKIN 10 SUPPRESSION OF MONOCYTE PROSTAGLANDIN-H SYNTHASE-2 - MECHANISM OF INHIBITION OF PROSTAGLANDIN-DEPENDENT MATRIX METALLOPROTEINASE PRODUCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROPHAGE COLLAGENASE PRODUCTION; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA; CYTOKINE PRODUCTION; B-CELLS; ACTIVATED MACROPHAGES; ALVEOLAR MACROPHAGES; INTERFERON-GAMMA; GENE-EXPRESSION; CYCLOOXYGENASE AB Monocytes/macrophages are associated with chronic inflammatory lesions, such as periodontal disease and rheumatoid arthritis, in which there is extensive connective tissue destruction. Stimulation of human monocytes results in the production of matrix metalloproteinases (MMPs) via a prostaglandin E(2) (PGE(2))-cAMP-dependent pathway. Modulation of many monocyte functions by interleukin 10 (IL-10) suggested that this cytokine may influence the signal transduction pathway leading to the production of MMPs by monocytes. Preincubation of monocytes with IL-10 for 1 h prior to stimulation with ConA resulted in significant inhibition of prostaglandin H synthase-2 (PGHS-2, the inducible form of prostaglandin synthase). In contrast, PGHS-1, the constitutive PGHS, was not affected by IL-10. Suppression of PGHS-2 mRNA and protein levels was detected at 1 ng/ml of IL-10 with maximal inhibition at 20 ng/ml Nuclear run-on transcription assays performed on monocytes exposed to ConA or the combination of ConA and IL-10 indicated that IL-10 treatment suppressed PGHS-2 expression at the level of transcription. Attenuation of PGHS-2 by IL-10 was accompanied by decreased prostaglandin production, including PGE(2). The decrease in prostaglandin production was primarily related to the effect of IL-10 on PGHS-2 since the release of arachidonic acid was unaffected by this cytokine. The inhibition of PGE(2) production by IL-10 resulted in the suppression of mRNA and protein for interstitial collagenase and 92-kDa type IV collagenase/ gelatinase (gelatinase B). This conclusion is supported by the ability of exogenously added PGE(2) or dibutyryl cAMP to restore the production of MMPs in IL-10-treated monocytes. Additionally, PGHS-2 was also restored by PGE(2) or dibutyryl cAMP, indicating that PGHS-2 is regulated through a PGE(2)-cAMP amplification pathway. These data add further support to the anti-inflammatory properties of IL-10. C1 NCI,PATHOL LAB,EXTRACELLULAR MATRIX PATHWAY SECT,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. RP MERTZ, PM (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,9000 ROCKVILLE PIKE,BLDG 30,RM 325,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 62 TC 170 Z9 171 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 21322 EP 21329 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300075 PM 8063757 ER PT J AU MURPHY, JE HANOVER, JA FROEHLICH, M DUBOIS, G KEEN, JH AF MURPHY, JE HANOVER, JA FROEHLICH, M DUBOIS, G KEEN, JH TI CLATHRIN ASSEMBLY PROTEIN AP-3 IS PHOSPHORYLATED AND GLYCOSYLATED ON THE 50-KDA STRUCTURAL DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINKED N-ACETYLGLUCOSAMINE; NUCLEAR-PORE; O-GLCNAC; CYTOPLASMIC GLYCOPROTEINS; MONOCLONAL-ANTIBODIES; INTACT NEURONS; CONTAIN; IDENTIFICATION; RESIDUES; CLONING AB AP-3 (AP180) in rat sympathetic neurons maintained in culture was analyzed by pulse-chase labeling with [S-35]methionine to look for post-translational modifications. At early times, two lower molecular weight precursors of the mature species were detected. By 10 min, all of the AP-3 was found in the mature form which is stable for at least 9 h. me show here that at least one of these processing events is due to the addition of O-linked N-acetylglucosamine (GlcNAc) which is present on the mature form of the protein. Wheat germ agglutinin, a GlcNAc-specific probe, bound to AP-3 and the binding was blocked by excess GlcNAc but not by excess mannose. Purified AP-3, and AP-3 in coated vesicles derived from bovine brain. served as substrates for beta-D-galactosyltransferase which is specific for terminal GlcNAc residues. Analysis of the disaccharide released by beta-elimination indicated that single GlcNAc residues are attached to AP-3 through an O-glycosidic linkage to threonine or serine residues. In vivo P-32-labeled AP-3, the result of serine phosphorylation (Keen J. H., and Black, M. M. (1986) J. Cell Biol. 102, 1325-1333), bound to wheat germ agglutinin-Sepharose indicating that phosphorylation and glycosylation can occur simultaneously on the same molecule. Both modifications have been mapped to the central 50-kDa structural domain that is responsible for the anomalous migration of AP-3. Consistent with localization to the nonclathrin binding domain, the O-GlcNAc modification does not play a discernible role in the interaction of AP-3 with clathrin. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. FU NIGMS NIH HHS [GM-28526] NR 37 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 19 PY 1994 VL 269 IS 33 BP 21346 EP 21352 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC403 UT WOS:A1994PC40300078 PM 8063760 ER PT J AU LUNNEY, EA HAGEN, SE DOMAGALA, JM HUMBLET, C KOSINSKI, J TAIT, BD WARMUS, JS WILSON, M FERGUSON, D HUPE, D TUMMINO, PJ BALDWIN, ET BHAT, TN LIU, BS ERICKSON, JW AF LUNNEY, EA HAGEN, SE DOMAGALA, JM HUMBLET, C KOSINSKI, J TAIT, BD WARMUS, JS WILSON, M FERGUSON, D HUPE, D TUMMINO, PJ BALDWIN, ET BHAT, TN LIU, BS ERICKSON, JW TI A NOVEL NONPEPTIDE HIV-1 PROTEASE INHIBITOR - ELUCIDATION OF THE BINDING MODE AND ITS APPLICATION IN THE DESIGN OF RELATED ANALOGS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; CRYSTAL-STRUCTURE; ANTIVIRAL ACTIVITY; 4-HYDROXYCOUMARINS; DERIVATIVES; PROTEINASE; RESOLUTION; PEPTIDE AB HIV-1 protease has been identified as a significant target enzyme in AIDS research. While numerous peptide-derived inhibitors have been described, the identification of a nonpeptide inhibitor remains an important goal. Using an HIV-1 protease mass screening technique, 4-hydroxy-3-(3-phenoxypropyl)-2H-1-benzopyran-2-one (1) was identified as a nonpeptide competitive inhibitor of the enzyme. Employing a Monte Carlo-based docking procedure, the coumarin was docked in the active site of the enzyme, revealing a binding mode that was later confirmed by the X-ray crystal analysis, Several analogs were prepared to test the binding interactions and improve the overall binding affinity. The most active compound in the study was 4,7-dihydroxy-3-[4-(2-methoxyphenyl)butyl]-2H-1-benzopyran-2-one (31). C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. RP LUNNEY, EA (reprint author), PARKE DAVIS PHARMACEUT RES,2800 PLYMOUTH RD,ANN ARBOR,MI 48105, USA. NR 43 TC 79 Z9 84 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 AUG 19 PY 1994 VL 37 IS 17 BP 2664 EP 2677 DI 10.1021/jm00043a006 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PD149 UT WOS:A1994PD14900006 PM 8064795 ER PT J AU PALUMBO, A NAPOLITANO, A DEMARTINO, L VIEIRA, W HEARING, VJ AF PALUMBO, A NAPOLITANO, A DEMARTINO, L VIEIRA, W HEARING, VJ TI SPECIFIC INCORPORATION OF 2-THIOURACIL INTO BIOLOGICAL MELANINS SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE MELANIN; THIOURACIL; MELANOGENESIS; PIGMENTATION; MELANOMA ID NEUTRON-CAPTURE THERAPY; MELANOMA-CELLS; CYTO-TOXICITY; TYROSINASE; MELANOCYTES; DOPA; MICE; USA AB 2-Thiouracil (TU), an antithyroid drug, is generally recognized as a highly specific melanoma seeker owing to its capability of being selectively accumulated into active melanin-producing tissues. We recently reported evidence that in vitro TU is capable of reacting with dopaquinone (DQ), an early intermediate in melanin biosynthesis, to give an addition product characterized as 6-S-thiouracildopa (TD). However, several aspects of the mechanism of the uptake of TU into melanin in vivo still need to be clarified. We report here the extremely rapid incorporation of [2-C-14]thiouracil into melanoma tumors growing subcutaneously in mice and show its selective accumulation into melanin by isolation and purification of the pigment fraction. Formation of the TD adduct in the tumor was examined by HPLC analysis of the soluble fractions of the tissue homogenates: however, no trace of TD could be detected on account of its rapid oxidation by the melanogenic enzyme tyrosinase, as evidenced by in vitro kinetic measurements. Monitoring the course of the tyrosinase-catalyzed oxidation of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the presence of TU, at various molar ratios, provided evidence for the ability of the drug to affect melanogenesis by interaction with biosynthetic intermediates beyond the DQ stage, suggesting other possible modes for its chemical binding to the growing pigment. C1 UNIV NAPLES, DEPT ORGAN & BIOL CHEM, I-80134 NAPLES, ITALY. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP PALUMBO, A (reprint author), Staz Zool Anton Dohrn, DEPT BIOCHEM, VILLA COMUNALE, I-80121 NAPLES, ITALY. RI Napolitano, Alessandra /E-9761-2011 NR 30 TC 17 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD AUG 18 PY 1994 VL 1200 IS 3 BP 271 EP 276 DI 10.1016/0304-4165(94)90167-8 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PE781 UT WOS:A1994PE78100006 PM 8068712 ER PT J AU NAKAJIMA, T WANG, RS ELOVAARA, E GONZALEZ, FJ GELBOIN, HV VAINIO, H AOYAMA, T AF NAKAJIMA, T WANG, RS ELOVAARA, E GONZALEZ, FJ GELBOIN, HV VAINIO, H AOYAMA, T TI CYP2C11 AND CYP2B1 ARE MAJOR CYTOCHROME-P450 FORMS INVOLVED IN STYRENE OXIDATION IN LIVER AND LUNG MICROSOMES FROM UNTREATED RATS, RESPECTIVELY SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE MONOCLONAL ANTIBODY; ETHANOL; PHENOBARBITAL; 3-METHYLCHOLANTHRENE; ENZYME INDUCTION; METABOLIC INTERACTION ID ANTIBODY-DIRECTED CHARACTERIZATION; MONOCLONAL-ANTIBODIES; ISOZYMES; METABOLISM; ENZYMES; BENZENE; HYDROCARBONS; EXPRESSION; TOLUENE; ETHANOL AB The contribution of cytochrome P450s (P450s) to the formation of styrene glycol from styrene in rat liver microsomes was investigated using monoclonal antibodies to P450s. Anti-CYP2E1 inhibited the formation to a similar extent in ethanol-treated microsomes and in control microsomes in terms of percentage inhibition, whereas to a greater extent in the former than the latter in terms of net inhibition, and only at low substrate concentration. Anti-CYP2C11/6 also inhibited the formation in control and in ethanol-treated microsomes at both low and high concentrations of styrene, and the net degree of inhibition was greater than that obtained with anti-CYP2E1, even in ethanol-treated microsomes where CYP2E1 was induced. Anti-CYP2B 1/2 and anti-CYP1A1/2 inhibited the formation only in phenobarbital (PB)- and 3-methylcholanthrene (MC)-induced microsomes, respectively. These results suggest that (1) at least four P450s, CYP2C11/6, CYP2E1, CYP2B1/2 and CYP1A1/2, contribute to the metabolism of styrene, (2) CYP2C11/6, which probably corresponds to CYP2C11, is the major form of P450 responsible for the metabolism in untreated rat liver microsomes, and also in those treated with ethanol. Anti-CYP2E1 inhibited styrene oxidation more prominently in microsomes from styrene-treated rats than in those from control rats at a low substrate concentration. Although styrene treatment did not influence the total metabolism of styrene in liver microsomes at a high substrate concentration, inhibition of the metabolism by anti-CYP2C11/6 decreased with increasing styrene dose, whereas that by anti-CYP2B1/2 increased, suggesting that styrene treatment increases CYP2B1/2 but decreases CYP2C11/ 6 in rat liver, and the major form of P450 which mediates styrene oxidation is CYP2B1/2 after the treatment. Only anti-CYP2B1/2, which probably corresponds to CYP2B1, inhibited styrene oxidation in lung microsomes from untreated and even styrene-treated rats. Thus, the major form of P450 responsible for the metabolism of styrene is different in each tissue. C1 SHINSHU UNIV,SCH MED,DEPT BIOCHEM,MATSUMOTO,NAGANO 390,JAPAN. INST OCCUPAT HLTH,DEPT IND HYG & TOXICOL,SF-00250 HELSINKI,FINLAND. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. INT AGCY RES CANC,F-69372 LYON,FRANCE. RP NAKAJIMA, T (reprint author), SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NR 27 TC 54 Z9 55 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 17 PY 1994 VL 48 IS 4 BP 637 EP 642 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE244 UT WOS:A1994PE24400002 PM 8080435 ER PT J AU ELANI, D JACOBSON, KA SHAINBERG, A AF ELANI, D JACOBSON, KA SHAINBERG, A TI CHARACTERIZATION OF ADENOSINE RECEPTORS IN INTACT CULTURED HEART-CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CPX; HEART-RATE; NOREPINEPHRINE; THYROID HORMONES ID MAMMALIAN VENTRICULAR MYOCYTES; ADENYLATE-CYCLASE ACTIVITY; CHICK ATRIAL MYOCYTES; GTP-BINDING PROTEINS; CORONARY BLOOD-FLOW; RADIOLIGAND BINDING; MYOCARDIAL-CELLS; GUINEA-PIGS; RAT; CONTRACTILITY AB Adenosine receptors were studied on heart cells grown in cultures by the radioligand binding technique. We used the hydrophilic A(1) adenosine receptor radioligand [H-3]-8-cyclopentyl-1,3-dipropylxanthine ([H-3]CPX), to monitor the level of the receptors on intact cardiocytes. The binding showed high affinity (K-d = 0.13 nM) and the number of [H-3]CPX binding sites (B-max) was 23.1 fmol/dish (21 fmol/mg protein). The K-i of the agonists R-N-6-(2-phenylisopropyl)-adenosine (R-PIA) and S-N-6-(2-phenylisopropyl)-adenosine (S-PIA), and of the antagonists CPX and theophylline were 3.57, 49.0, 1.63 and 4880 nM, respectively. The number of adenosine receptors was very low during the first days in cultures (5 fmol/dish) and increased gradually until it reached a plateau on days 8-10. Treatment with norepinephrine or isoproterenol which accelerated the rate of contractions, induced up regulation of the receptors. B-max increased 2-3 fold by application of norepinephrine for 4 days, while receptor affinity to the radioligand was unaffected. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity increased only by 22 and 38%, respectively. Similarly, 3 days treatment with triiodothyronine (T-3, 10(-8) M), which also accelerated heart rate, increased the number of adenosine receptors by 56% without a significant change in the affinity of the receptors to [H-3]CPX. Carbamylcholine (5 x 10(-6) M), which reduced the rate of heart contractions, caused 26% down regulation while the affinity of the receptors remained unchanged. It is concluded that there is a linkage between the rate of cardiac contractions and the level of adenosine receptors. Thus, the level of adenosine receptors may respond to drug-induced chronic changes in cardiac contractile activity so as to restore conditions to normal (basal) contractions. C1 BAR ILAN UNIV,OTTO MEYERHOF DRUG RECEPTOR CTR,DEPT LIFE SCI,IL-52900 RAMAT GAN,ISRAEL. NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 46 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 17 PY 1994 VL 48 IS 4 BP 727 EP 735 DI 10.1016/0006-2952(94)90050-7 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE244 UT WOS:A1994PE24400013 PM 8080445 ER PT J AU FULLER, RK GORDIS, E AF FULLER, RK GORDIS, E TI REFINING THE TREATMENT OF ALCOHOL-WITHDRAWAL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DETOXIFICATION; TRIAL RP FULLER, RK (reprint author), NIAAA,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 13 TC 8 Z9 8 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 17 PY 1994 VL 272 IS 7 BP 557 EP 558 DI 10.1001/jama.272.7.557 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PB229 UT WOS:A1994PB22900035 PM 8046812 ER PT J AU KARP, JE MCCAFFREY, RP AF KARP, JE MCCAFFREY, RP TI NEW AVENUES OF TRANSLATIONAL RESEARCH IN LEUKEMIA AND LYMPHOMA - OUTGROWTH OF A LEUKEMIA-SOCIETY-OF-AMERICA NATIONAL-CANCER-INSTITUTE WORKSHOP SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FIBROBLAST GROWTH-FACTOR; MARROW STROMAL CELLS; HUMAN BONE-MARROW; INTERLEUKIN-2 RECEPTOR; GENE-TRANSFER; ANTIBODY; THERAPY; DEATH C1 BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,MED ONCOL SECT,BOSTON,MA. RP KARP, JE (reprint author), NCI,OFF DIRECTOR,BLDG 31,RM 11A29,BETHESDA,MD 20892, USA. NR 52 TC 5 Z9 5 U1 2 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 17 PY 1994 VL 86 IS 16 BP 1196 EP 1201 DI 10.1093/jnci/86.16.1196 PG 6 WC Oncology SC Oncology GA PB103 UT WOS:A1994PB10300007 PM 8040886 ER PT J AU NAYFIELD, SG BONGIOVANNI, GC ALCIATI, MH FISCHER, RA BERGNER, L AF NAYFIELD, SG BONGIOVANNI, GC ALCIATI, MH FISCHER, RA BERGNER, L TI STATUTORY REQUIREMENTS FOR DISCLOSURE OF BREAST-CANCER-TREATMENT ALTERNATIVES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID GEOGRAPHIC-VARIATION; INFORMED CONSENT; CLINICAL-TRIALS; SURGERY; MANAGEMENT; MASTECTOMY; CHOICE; RADIOTHERAPY; EXPERIENCE; DIAGNOSIS AB Therapeutic options for breast cancer, particularly for early-stage disease, and increased patient participation in medical decision-making have oriented state legislatures toward ensuring that women with breast cancer have adequate information about treatment alternatives. Currently, 18 states have enacted statutes regarding physician disclosure of treatment alternatives to breast cancer patients. This paper reviews these statutes in the context of the requirements imposed on the physician as health care provider and the content of medical information presented to the patient as a consequence of the laws. State statutes were identified through the National Cancer Institute's State Cancer Legislative Database, and the statutory requirements were analyzed. For statutes requiring development of a written summary of treatment alternatives, the most recent summary was obtained through the responsible state agency, and informational content was analyzed for relevance to treatment decisions in early-stage disease. As a group, these laws address informed consent for treatment, physician behavior within the patient-physician relationship, and the medical information upon which treatment decisions are based. Individual statutes vary in the scope of the issues addressed, particularly in the responsibility placed on physicians, and treatment option summaries developed in response to this legislation vary widely in content and scope. Despite broad implications of these statutes in oncology practice, little is known about their effects on breast cancer care. Additional research is needed to define the impact of these statutes on breast cancer care, as such legislation is considered by other states for this and other diseases. C1 NCI,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,PUBL HLTH APPLICAT RES BRANCH,BETHESDA,MD 20892. VANDERBILT UNIV,SCH LAW,NASHVILLE,TN 37240. NATL OPINION RES CTR,WASHINGTON,DC. MAYATECH CORP,SILVER SPRING,MD. OI Alciati, Marianne/0000-0001-6294-1090 NR 43 TC 46 Z9 47 U1 1 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 AUG 17 PY 1994 VL 86 IS 16 BP 1202 EP 1208 DI 10.1093/jnci/86.16.1202 PG 7 WC Oncology SC Oncology GA PB103 UT WOS:A1994PB10300008 PM 8040887 ER PT J AU WARD, JM FOX, JG ANVER, MR HAINES, DC GEORGE, CV COLLINS, MJ GORELICK, PL NAGASHIMA, K GONDA, MA GILDEN, RV TULLY, JG RUSSELL, RJ BENVENISTE, RE PASTER, BJ DEWHIRST, FE DONOVAN, JC ANDERSON, LM RICE, JM AF WARD, JM FOX, JG ANVER, MR HAINES, DC GEORGE, CV COLLINS, MJ GORELICK, PL NAGASHIMA, K GONDA, MA GILDEN, RV TULLY, JG RUSSELL, RJ BENVENISTE, RE PASTER, BJ DEWHIRST, FE DONOVAN, JC ANDERSON, LM RICE, JM TI CHRONIC ACTIVE HEPATITIS AND ASSOCIATED LIVER-TUMORS IN MICE CAUSED BY A PERSISTENT BACTERIAL-INFECTION WITH A NOVEL HELICOBACTER SPECIES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CAMPYLOBACTER-JEJUNI; SP-NOV; VIRUS; PYLORI; CARCINOGENESIS; EPITHELIUM; IMMUNOBLOT; MUSTELAE; FERRETS; MUCOSA AB Background: In the autumn of 1992, a novel form of chronic, active hepatitis of unknown etiology was discovered in mice at the National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, Md. A high incidence of hepatocellular tumors occurred in affected animals. The disease entity was originally identified in A/JCr mice that were untreated controls in a long-term toxicologic study. Purpose: Our original purpose was to determine the origin and etiology of the chronic hepatitis and to quantify its association with hepatocellular tumors in mice of low liver tumor incidence strains. After a helical microorganism was discovered in hepatic parenchyma of diseased mice, we undertook characterization of the organism and investigation of its relationship to the disease process. Methods: Hepatic histopathology of many strains of mice and rats, as well as guinea pigs and Syrian hamsters, in our research and animal production facilities was reviewed. Steiner's modification of the Warthin-Starry stain and transmission electron microscopy were used to identify bacteria in the liver. We transmitted the hepatitis with liver suspensions from affected mice and by inoculation with bacterial cultures. Bacteria were cultivated on blood agar plates maintained under anaerobic or microaerophilic conditions and characterized morphologically, biochemically, and by 16S rRNA sequence. Results: We report here the isolation of a new species of Helicobacter (provisionally designated Helicobacter hepaticus sp. nov.) that selectively and persistently colonizes the hepatic bile canaliculi of mice (and possibly the intrahepatic biliary system and large bower), causing a morphologically distinctive pattern of chronic, active hepatitis and associated with a high incidence of hepatocellular neoplasms in infected animals. Conclusions: The novel Helicobacter is a likely candidate for the etiology of hepatocellular tumors in our mice. The Helicobacter-associated chronic active hepatitis represents a new model to study mechanisms of carcinogenesis by this genus of bacteria. Implications: Adenocarcinoma of the stomach, the second most prevalent of all human malignancies worldwide, is associated with infection at an early age with Helicobacter pylori. Infection leads to several distinctive forms of gastritis, including chronic atrophic gastritis, which is a precursor of adenocarcinoma. H. hepaticus infection in mice constitutes the only other parallel association between a persistent bacterial infection and tumor development known to exist naturally. Study of the H. hepaticus syndrome of chronic active hepatitis and liver tumors in mice may yield insights into the role of H. pylori in human stomach cancer and gastric lymphoma. C1 NCI,OFF LAB ANIM SCI,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NIAID,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,HARLAN SPRAGUE INC,FREDERICK,MD. FORSYTH DENT CTR,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,FAIRVIEW 201,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01CO74102] NR 38 TC 313 Z9 326 U1 0 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 17 PY 1994 VL 86 IS 16 BP 1222 EP 1227 DI 10.1093/jnci/86.16.1222 PG 6 WC Oncology SC Oncology GA PB103 UT WOS:A1994PB10300011 PM 8040890 ER PT J AU LETEURTRE, F KOHLHAGEN, G PAULL, KD POMMIER, Y AF LETEURTRE, F KOHLHAGEN, G PAULL, KD POMMIER, Y TI TOPOISOMERASE II INHIBITION AND CYTOTOXICITY OF THE ANTHRAPYRAZOLES DUP-937 AND DUP-941 (LOSOXANTRONE) IN THE NATIONAL-CANCER-INSTITUTE PRECLINICAL ANTITUMOR DRUG DISCOVERY SCREEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-CELL-LINES; DNA CLEAVAGE; BIOCHEMICAL PHARMACOLOGY; LEUKEMIA-CELLS; BREAST-CANCER; MITOXANTRONE; AGENTS; BINDING; PHARMACOKINETICS; IDENTIFICATION AB Background: The cumulative cardiotoxicity of anthracyclines is thought to result from the generation of free radicals. New DNA topoisomerase II inhibitors less prone to redox reactions, such as mitoxantrone and more recently the anthrapyrazoles, were developed to circumvent this toxicity. Purpose: Two anthrapyrazoles currently in clinical evaluation, DuP 941 (Losoxantrone) and DuP 937, were compared to other topoisomerase II inhibitors with respect to their cytotoxic potency and selectivity and with respect to topoisomerase II inhibition. Methods: Cytotoxicity was tested in the 60 cell lines of the National Cancer Institute preclinical antitumor drug discovery screen (NCI screen). The potency of anthrapyrazoles to inhibit purified topoisomerase II was determined, The specificity of drug-induced topoisomerase II pattern of cleavage, one of the cellular determinants of cytotoxicity, was investigated in human c-myc DNA. Results: Using the COMPARE analysis, we found that the most closely related cytotoxic profiles in the NCI screen were between the anthrapyrazoles and mitoxantrone. Among topoisomerase II inhibitors, the cytostatic potency was by decreasing order: mitoxantrone; doxorubicin, which was slightly greater than DuP 941, azatoxin; DuP 937; and amsacrine, which was much greater than VP-16. The potency of mitoxantrone and anthrapyrazoles to generate DNA double-strand breaks, by induction of the topoisomerase II cleavable complexes in nuclear extracts, was in agreement with cytotoxicity. Sequencing of drug-induced topoisomerase II cleavages in c-myc DNA showed a common cleavage pattern for anthrapyrazoles and mitoxantrone. This pattern was different from the patterns obtained with other topoisomerase II inhibitors. Conclusion: At the molecular and cellular levels, anthrapyrazoles are potent topoisomerase II inhibitors closely related to mitoxantrone. Implications: These results validate the COMPARE analysis using the NCI screen to predict molecular mechanisms of drug action. Anthrapyrazoles, which are unlikely to produce free radicals, might be useful in the same indications as mitoxantrone, especially for patients with cardiac risks, for pediatric patients, and for patients treated with intensified protocols. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. NR 37 TC 59 Z9 59 U1 0 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 AUG 17 PY 1994 VL 86 IS 16 BP 1239 EP 1244 DI 10.1093/jnci/86.16.1239 PG 6 WC Oncology SC Oncology GA PB103 UT WOS:A1994PB10300014 PM 8040892 ER PT J AU WU, AM CSAKO, G HERP, A AF WU, AM CSAKO, G HERP, A TI STRUCTURE, BIOSYNTHESIS, AND FUNCTION OF SALIVARY MUCINS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Review DE OLIGOSACCHARIDES; TANDEM SEQUENCES; CDNA; RECEPTORS; BLOOD GROUP ANTIGENS; IMMUNE RESPONSE ID BOVINE SUBMAXILLARY MUCIN; SECRETORY IMMUNOGLOBULIN-A; SUBMANDIBULAR-SUBLINGUAL SALIVA; HUMAN TRACHEOBRONCHIAL MUCIN; O-LINKED GLYCOPROTEINS; BLOOD-GROUP-H; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; MOLECULAR-CLONING; INTESTINAL MUCIN AB The glandular secretions of the oral cavity lining the underlying buccal mucosa are highly specialized fluids which provide lubrication, prevent mechanical damage, protect efficiently against viral and bacterial infections, and promote the clearance of external pollutants. This mucus blanket contains large glycoproteins termed mucins which contribute greatly to the viscoelastic nature of saliva and affect its complex physiological. activity. The protein core of mucins consists of repetitive sequences, rich in O-glycosylated serine and threonine, and containing many helix-breaking proline residues. These features account for the extended, somewhat rigid structure of the molecule, a high hydrodynamic volume, its high buoyant density, and high viscosity. The oligosaccharide moiety of salivary mucins accounts for up to 85% of their weight. The oligosaccharide side chains exhibit an astonishing structural diversity. The isolation, composition, structure, molecular characteristics, and functional relevance of salivary mucins and their constituents is discussed in relation to recent advancements in biochemistry and molecular biology. C1 NIH,WG MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. CHANG GUNG COLL MED & TECHNOL,GLYCOIMMUNOCHEM RES LAB,TAYUAN,TAIWAN. NR 164 TC 82 Z9 84 U1 0 U2 20 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG 17 PY 1994 VL 137 IS 1 BP 39 EP 55 DI 10.1007/BF00926038 PG 17 WC Cell Biology SC Cell Biology GA PL162 UT WOS:A1994PL16200006 PM 7845377 ER PT J AU CHEN, HW CHEN, CL CHOU, JY AF CHEN, HW CHEN, CL CHOU, JY TI CHARACTERIZATION OF 2 PROMOTERS OF A RAT PREGNANCY-SPECIFIC GLYCOPROTEIN GENE SO BIOCHEMISTRY LA English DT Article ID CARCINOEMBRYONIC ANTIGEN; ADHESION MOLECULE; NUCLEAR FACTORS; CONTROL ELEMENT; TATA BOX; FAMILY; TRANSCRIPTION; EXPRESSION; BETA-1-GLYCOPROTEIN; PROTEIN AB Pregnancy-specific glycoproteins (PSGs) are the major placental glycoproteins, that together with the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. In order to develop an animal model for understanding the molecular mechanisms underlying the control of PSG expression, we isolated and characterized cDNA and genomic clones encoding a rodent PSG, rnCGM3. The rnCGM3 cDNA is 2761 bp in length and contains an open reading frame that encodes a 475 amino acid polypeptide with a domain arrangement of L(1)N(1)-L(2)N(2)-L(3)N(3)-A. The sequence in the 5'-untranslated and L(1) regions of rnCGM3 is identical to a previously identified cDNA, rnCGM6. The transcription initiation sites of both genes are located at nucleotide -197 upstream of the translation start site. In transient transfection assays using a chloramphenicol acetyltransferase (CAT) reporter gene, we demonstrated that DNA elements at nucleotides -326 to -185 (PI) and -147 and -86 (PII) relative to the translation start site of rnCGM3 could both function as promoters. The downstream promoter, PII, which is located within the first exon, shares high sequence identity with the minimal promoters of human PSG genes. Electrophoretic mobility shift assays (EMSAs) showed that protein factors in placental cell extracts formed three complexes (PIICI, PIICII, and PIICIII) with the PII promoter element. The PIICIII complex was also observed by DNase I footprinting analysis. Unlike PII, the upstream promoter, PI, contains a TATA box. DNase I footprinting analysis revealed two nuclear protein binding sites at nucleotides -311 to -290 (PISI) and -257 to -239 (PISII) in PI, EMSAs showed that protein factors in placental cell extracts bound to both sites and deletion of either site markedly reduced CAT expression. PISII contains a palindromic motif, TGTTGCTCAACA, and protein cross-linking and Southwestern hybridization analyses demonstrated that the protein factor binding to PISII had an apparent molecular mass of 40 kDa. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV FLORIDA,COLL VET MED,DEPT LARGE ANIM CLIN SCI,GAINESVILLE,FL 32610. NR 46 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 16 PY 1994 VL 33 IS 32 BP 9615 EP 9626 DI 10.1021/bi00198a030 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC545 UT WOS:A1994PC54500030 PM 8068638 ER PT J AU BHAT, MK ASHIZAWA, K CHENG, SY AF BHAT, MK ASHIZAWA, K CHENG, SY TI PHOSPHORYLATION ENHANCES THE TARGET GENE SEQUENCE-DEPENDENT DIMERIZATION OF THYROID-HORMONE RECEPTOR WITH RETINOID-X RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HETERODIMER; TRANSACTIVATION; HORMONE RESPONSE ELEMENT; DNA BINDING; 9-CIS-RETINOIC ACID ID DNA-BINDING; NUCLEAR RECEPTOR; ACID; HETERODIMERIZATION; TRANSCRIPTION; INVITRO; DOMAIN; LIGAND; SITE AB To understand the molecular basis of the phosphorylation-enhanced transcriptional activity of human thyroid hormone nuclear receptor subtype beta 1 (hTR beta 1), we studied the effect of phosphorylation on the interaction of hTR beta 1 with the retinoid X receptor beta (RXR beta). In vitro, the extent of hTR beta 1.RXR beta heterodimer bound to various thyroid hormone response elements (TREs) was compared before and after phosphorylation of hTR beta 1. Without phosphorylation, hTR beta 1.RXR beta heterodimer was barely detectable under the experimental conditions. After phosphorylation of hTR beta 1, heterodimer bound to (i) the chicken lysozyme gene TRE, (ii) a TRE consisting of direct repeats of half-site binding moths separated by four gaps, and (iii) a palindromic TRE was enhanced by approximately 10-, 7-, and 6-fold, respectively. The effect of phosphorylation on hTR beta 1.RXR beta heterodimerization was reversible. Dephosphorylation of the phosphorylated hTR beta 1 by alkaline phosphatase led to loss of the ability of hTR beta 1 to form a heterodimer with RXR beta in either the absence or the presence of DNA. These results indicate that the heterodimerization is enhanced by phosphorylation, To evaluate the effect of phosphorylation on the interaction of hTR beta 1 with RXR beta in vivo, we cotransfected hTR beta 1, RXR beta and TRE-chloramphenicol acetyltransferase (CAT) expression plasmids into CV-1 cells. CAT activity was assessed in the presence or absence of okadaic acid. Okadaic acid is a potent inhibitor of phosphatases 1 and 2A and increases the in vivo phosphorylation of hTR beta 1 by approximate to 10-fold. Using the CAT reporter gene under control of the TRE from the mafic enzyme gene, we found that RXR beta increased the okadaic acid-enhanced hTR beta 1-mediated CAT activity by 2- to 3-fold in the presence of 3,3',5-triiodo-L-thyronine, However, 9-cis-retinoic acid did not enhance the effect of okadaic acid. Our results indicate that phosphorylation is essential for the interaction of hTR beta 1 with RXR beta. Thus, phosphorylation plays a pivotal role in the gene-regulating activity of hTR beta 1. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 22 TC 47 Z9 47 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 7927 EP 7931 DI 10.1073/pnas.91.17.7927 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200021 PM 8058736 ER PT J AU LISZIEWICZ, J SUN, D WEICHOLD, FF THIERRY, AR LUSSO, P TANG, JY GALLO, RC AGRAWAL, S AF LISZIEWICZ, J SUN, D WEICHOLD, FF THIERRY, AR LUSSO, P TANG, JY GALLO, RC AGRAWAL, S TI ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE COMPLEMENTARY TO GAG MESSENGER-RNA BLOCKS REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN HUMAN PERIPHERAL-BLOOD CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; THERAPY ID CHRONICALLY INFECTED-CELLS; GENE-EXPRESSION; CULTURED-CELLS; OLIGONUCLEOTIDES; INHIBITION; REGION; RNA AB Gene-expression modulator 91 (GEM91) is a 25-nt antisense oligodeoxynucleotide phosphorothioate complementary to the Gag mRNA of human immunodeficiency virus type 1 (HIV-1). Cellular uptake and intracellular distribution of GEM91 within cells suggest that this oligomer is readily available for antisense activity. GEM91 inhibited HIV-1 replication in a dose-dependent and sequence-specific manner. In a comparative study, 2 mu M GEM91 was as effective as 5 mu M 3'-azido-3'-deoxythymidine in blocking virus replication during the 28-day treatment of an HIV-1-infected T-cell line. GEM91 also completely inhibited (> 99%) the growth of three different HIV-1 isolates in primary lymphocytes and prevented the cytopathic effect of the virus in primary CD4(+) T cells. Similarly, treatment with GEM91 for 3 weeks of HIV-1/BaL-infected primary macrophages blocked virus replication. Based on GEM91 anti-HIV-activity, safety, and pharmacokinetic profile in animals, a clinical trial was started using this compound as an antisense oligonucleotide drug for the treatment of the acquired immunodeficiency syndrome. C1 HYBRIDON INC,WORCESTER,MA 01605. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI thierry, alain/F-9492-2014 NR 29 TC 97 Z9 99 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 7942 EP 7946 DI 10.1073/pnas.91.17.7942 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200024 PM 8058738 ER PT J AU LOUIS, JM NASHED, NT PARRIS, KD KIMMEL, AR JERINA, DM AF LOUIS, JM NASHED, NT PARRIS, KD KIMMEL, AR JERINA, DM TI KINETICS AND MECHANISM OF AUTOPROCESSING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROTEASE FROM AN ANALOG OF THE GAG-POL POLYPROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETROVIRAL PROTEASES; HIV-1 PROTEINASE; VIRAL INFECTIVITY; CRYSTAL-STRUCTURE; MALTOSE-BINDING; RESOLUTION; PEPSINOGEN; ASSAY; PEPSTATIN; CLEAVAGE AB Upon renaturation, the polyprotein MBP-Delta TF-Protease-Delta Pol, consisting of HIV-1 protease and short native sequences from the trans-frame protein (Delta TF) and the polymerase (Delta Pol) fused to the maltose-binding protein (MBP) of Escherichia coli, undergoes autoprocessing to produce the mature protease in two steps. The initial step corresponds to cleavage of the N-terminal sequence to release the protein intermediate Protease-Delta Pol, which has enzymatic activity comparable to that of the mature enzyme. Subsequently, the mature enzyme is formed by a slower cleavage at the C terminus. The rate of increase in enzymatic activity is identical to that of the appearance of MBP-Delta TF and the disappearance of the MBP-Delta TF-Protease-Delta Pol. Initial rates are linearly dependent on the protein concentration, indicating that the N-terminal cleavage is first-order in protein concentration. The reaction is competitively inhibited by pepstatin A and has a pH rate profile similar to that of the mature enzyme. These results and molecular modeling studies are discussed in terms of a mechanism in which a dimeric full-length fusion protein must form prior to rate-limiting intramolecular cleavage of the N-terminal sequence that leads to an increase in enzymatic activity. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 26 TC 79 Z9 79 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 7970 EP 7974 DI 10.1073/pnas.91.17.7970 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200030 PM 8058744 ER PT J AU BLUML, K MUTSCHLER, E WESS, J AF BLUML, K MUTSCHLER, E WESS, J TI INSERTION MUTAGENESIS AS A TOOL TO PREDICT THE SECONDARY STRUCTURE OF A MUSCARINIC RECEPTOR DOMAIN DETERMINING SPECIFICITY OF G-PROTEIN COUPLING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G PROTEIN-COUPLED RECEPTORS; PHOSPHATIDYLINOSITOL HYDROLYSIS; RECEPTOR; G PROTEIN INTERACTIONS; SITE-DIRECTED MUTAGENESIS ID BETA-ADRENERGIC-RECEPTOR; 3RD CYTOPLASMIC LOOP; ACETYLCHOLINE-RECEPTOR; PHOSPHATIDYLINOSITOL HYDROLYSIS; SYNTHETIC PEPTIDES; INTRACELLULAR LOOP; LIGAND-BINDING; AMINO-ACIDS; SELECTIVITY; ACTIVATION AB The N-terminal segment of the third intra cellular loop (i3) of muscarinic acetylcholine receptors and other G protein coupled receptors has been shown to largely determine the G-protein coupling selectivity displayed by a given receptor subtype. Based on secondary-structure prediction algorithms, we have tested the hypothesis that this region adopts an alpha-helical secondary structure. Using the rat m3 muscarinic receptor as a model system, a series of five mutant receptors, m3(+1A) to m3(+5A), were created in which one to five additional alanine residues were inserted between the end of the fifth transmembrane domain and the beginning of i3. We speculated that this manipulation should lead to a rotation of the N-terminal segment of the i3 domain (if it is in fact alpha-helically arranged), thus producing pronounced effects on receptor/G protein coupling. Pharmacological analysis of the various mutant receptors expressed in COS-7 cells showed that m3(+1A), m3(+3A), and m3(+4A) retained strong functional activity, whereas m3(+2A) and m3(+5A) proved to be virtually inactive. Helical wheel models show that this pattern is fully consistent with the notion that the N-terminal portion of i3 forms an amphiphilic alpha-helix and that the hydrophobic side of this helix represents the G protein recognition surface. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV FRANKFURT,DEPT PHARMACOL,D-60439 FRANKFURT,GERMANY. NR 35 TC 39 Z9 39 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 7980 EP 7984 DI 10.1073/pnas.91.17.7980 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200032 PM 8058746 ER PT J AU VERES, Z STADTMAN, TC AF VERES, Z STADTMAN, TC TI A PURIFIED SELENOPHOSPHATE-DEPENDENT ENZYME FROM SALMONELLA-TYPHIMURIUM CATALYZES THE REPLACEMENT OF SULFUR IN 2-THIOURIDINE RESIDUES IN TRANSFER-RNAS WITH SELENIUM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SELENO-TRANSFER-RNA SYNTHESIS ID TRANSFER-RNAS; ESCHERICHIA-COLI; 5-METHYLAMINOMETHYL-2-SELENOURIDINE; CHROMATOGRAPHY; BIOSYNTHESIS; NUCLEOSIDE; DONOR AB A tRNA-modifying enzyme tentatively termed tRNA 2-selenouridine synthase was purified by a five-step procedure that resulted in 50-60% pure preparations. This enzyme catalyzes the conversion of a 5-methylaminomethyl-2-thiouridine residue in the tRNA substrate to 5-methylaminomethyl-2-selenouridine. The selenium donor substrate for this reaction is shown to be selenophosphate which is formed from ATP and selenide by selenophosphate synthetase. Replacement of sulfur with selenium in tRNAs catalyzed by tRNA 2-selenouridine synthase occurs in the absence of ATP. The dependence of reaction velocity on selenophosphate concentration obeys Michaelis-Menten kinetics indicating an apparent K-m value of 17.1 mu M. Bulk thio-tRNA preparations from Escherichia coli and Salmonella typhimurium are equally effective as substrates for the selenium incorporation reaction. An intact 3' end of the tRNA molecule does not seem to be essential for selenium incorporation. Identity of the product of the reaction was confirmed by HPLC analysis of digests of [Se-75]seleno-tRNAs labeled by incubation with the purified enzyme. A labeled compound in the nucleoside mixture was coeluted with authentic 5-methylaminomethyl-2-selenouridine. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,CENT RES INST CHEM,H-1525 BUDAPEST,HUNGARY. NR 14 TC 25 Z9 27 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 8092 EP 8096 DI 10.1073/pnas.91.17.8092 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200055 PM 7520175 ER PT J AU MOLCHAN, SE SUNDERLAND, T MCINTOSH, AR HERSCOVITCH, P SCHREURS, BG AF MOLCHAN, SE SUNDERLAND, T MCINTOSH, AR HERSCOVITCH, P SCHREURS, BG TI A FUNCTIONAL ANATOMICAL STUDY OF ASSOCIATIVE LEARNING IN HUMANS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CLASSICAL CONDITIONING; AUDITORY CORTEX; CEREBELLUM; POSITRON EMISSION TOMOGRAPHY; REGIONAL CEREBRAL BLOOD FLOW ID INFERIOR TEMPORAL CORTEX; AUDITORY-CORTEX; INTRAVENOUS (H2O)-O-15; HIPPOCAMPAL-FORMATION; PREFRONTAL CORTEX; PET IMAGES; MEMORY; BRAIN; PATTERNS; 2-DEOXYGLUCOSE AB The purpose of the study was to map the functional neuroanatomy of simple associative learning in humans. Eyeblink conditioning was studied in eight normal volunteers using positron emission tomography and (H2O)-O-15. Regional cerebral blood flow was assessed during three sequential phases: (i) explicitly unpaired presentations of the unconditioned stimulus (air puff to the right eye) and conditioned stimulus (binaural tone), (ii) paired presentations of the two stimuli (associative teaming), and (iii) presentation of the conditioned stimulus alone. During associative learning, relative to the unpaired phase, blood now was significantly increased in primary auditory and left posterior cingulate cortices and significantly decreased in areas of the right cerebellar, right prefrontal, right parietal, and insular cortices and right neostriatum. The lateralization of the changes may relate to the functional organization of memory and learning processes in the brain. The activation in primary auditory cortex is an example, using a neuroimaging technique, of a learning-related change in primary sensory cortex in humans. The changes in areas such as the cerebellum, prefrontal cortex, and neostriatum provide support for their roles in associative learning as proposed by animal models. Moreover, these findings show that in humans, even simple classical conditioning involves distributed changes in multiple neural systems. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIH, DEPT NUCL MED, BETHESDA, MD 20892 USA. NINCDS, ADAPT SYST LAB, BETHESDA, MD 20892 USA. RP MOLCHAN, SE (reprint author), NIMH, CLIN SCI LAB,GERIATR PSYCHIAT SECT, 9000 ROCKVILLE PIKE,BLDG 10, ROOM 3D41, BETHESDA, MD 20892 USA. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662; Schreurs, Bernard/0000-0002-5776-0807 NR 46 TC 184 Z9 185 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 8122 EP 8126 DI 10.1073/pnas.91.17.8122 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200061 PM 8058767 ER PT J AU LI, CY PEOPLES, RW WEIGHT, FF AF LI, CY PEOPLES, RW WEIGHT, FF TI ALCOHOL ACTION ON A NEURONAL MEMBRANE-RECEPTOR - EVIDENCE FOR A DIRECT INTERACTION WITH THE RECEPTOR PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUROTRANSMITTER RECEPTOR; ION CHANNEL; MEMBRANE FLUIDITY; LIPID; HYDROPHOBICITY ID BULLFROG SENSORY NEURONS; ATP-ACTIVATED CHANNELS; CHAIN ALCOHOLS; ANESTHETICS; INTOXICATION; MECHANISMS; CURRENTS; CUTOFF; SERIES; RAT AB For almost a century, alcohols have been thought to produce their effects by actions on the membrane Lipids of central nervous system neurons-the well known ''lipid theory'' of alcohol action. The rationale for this theory is the correlation of potency with oil/water or membrane/buffer partition coefficient. Although a number of recent studies have shown that alcohols can affect the function of certain neuronal neurotransmitter receptors, there is no evidence that the alcohols interact directly with these membrane proteins. In the present study, we report that inhibition of a neuronal neurotransmitter receptor, an ATP-gated ion channel, by a series of alcohols exhibits a distinct cutoff effect. For alcohols with a molecular volume of less than or equal to 42.2 ml/mol, potency for inhibiting ATP-activated current was correlated with lipid solubility (order of potency: 1-propanol = trifluoroethanol > monochloroethanol > ethanol > methanol). However, despite increased lipid solubility, alcohols with a molecular volume of greater than or equal to 46.1 ml/mol (1-butanol, 1-pentanol, trichloroethanol, and dichloroethanol) were without effect on the ATP-activated current. The results suggest that alcohols inhibit the function of this neurotransmitter receptor by interacting with a small hydrophobic pocket on the receptor protein. RP LI, CY (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 35 TC 101 Z9 103 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 8200 EP 8204 DI 10.1073/pnas.91.17.8200 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200077 PM 8058780 ER PT J AU BUKH, J PURCELL, RH MILLER, RH AF BUKH, J PURCELL, RH MILLER, RH TI SEQUENCE-ANALYSIS OF THE CORE GENE OF 14 HEPATITIS-C VIRUS GENOTYPES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NON-A, NON-B HEPATITIS; GENETIC HETEROGENEITY; POLYMERASE CHAIN REACTION; PHYLOGENETIC TREE; TAXONOMY ID POLYMERASE CHAIN-REACTION; 5' NONCODING REGION; DISTINCT; SUBTYPES; PROTEINS; GENOME; ORGANIZATION; DIVERSITY; PRIMERS; ASSAY AB We previously sequenced the 5' noncoding region of 44 isolates of hepatitis C virus (HCV), as well as the envelope 1 (E1) gene of 51 HCV isolates, and provided evidence for the existence of at least 6 major genetic groups consisting of at least 12 minor genotypes of HCV (i.e., genotypes I/1a, II/1b, III/2a, IV/2b, 2c, V/3a, 4a-4d, 5a, and 6a), We now report the complete nucleotide sequence of the putative core (C) gene of 52 HCV isolates that represent all or these 12 genotypes as well as two additional genotypes provisionally designated 4e and 4f that we identified in this study. The phylogenetic analysis of the C gene sequences was in agreement with that of the E1 gene sequences. A major division in the genetic distance was observed between HCV isolates of genotype 2 and those of the other genotypes in analysis of both the E1 and C genes. The C gene sequences of 9 genotypes have not been reported previously (i.e., genotypes 2c, 4a-4f, 5a, and 6a). Our analysis indicates that the C gene-based methods currently used to determine the HCV genotype, such as PCR with genotype-specific primers, should be revised in light of these data, We found that the predicted C gene was exactly 573 nt long in all 52 HCV isolates, with an N-terminal start codon and no in-frame stop codons. The nucleotide and predicted amino acid identities of the C gene sequences were in the range of 79.4-99.0% and 85.3-100%, respectively. Furthermore, we mapped universally conserved, as well as genotype-specific, nucleotide and deduced amino acid sequences of the C gene. The predicted C proteins of the different HCV genotypes shared the following features: (i) high content of proline residues, (ii) high content of arginine and lysine residues located primarily in three domains with 10 such residues invariant at positions 39-62, (iii) a cluster of 5 conserved tryptophan residues, (iv) two nuclear localization signals and a DNA-binding motif, (v) a potential phosphorylation site with a serine-proline motif, and (vi) three conserved hydrophilic domains that have been shown by others to contain immunogenic epitopes. Thus, we have extended analysis of the predicted C protein of HCV to all of the recognized genotypes, confirmed the existence of highly conserved regions of this important structural protein, and demonstrated that the genetic relatedness of HCV isolates is equivalent when analyzing the most conserved (i.e., C) and the most variable (i.e., E1) genes of the HCV genome. RP BUKH, J (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 26 TC 254 Z9 261 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 16 PY 1994 VL 91 IS 17 BP 8239 EP 8243 DI 10.1073/pnas.91.17.8239 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PC242 UT WOS:A1994PC24200085 PM 8058787 ER PT J AU DOMANSKI, MJ FRIEDMAN, LM AF DOMANSKI, MJ FRIEDMAN, LM TI RELATIVE ROLE OF METAANALYSIS AND RANDOMIZED CONTROLLED TRIALS IN THE ASSESSMENT OF MEDICAL THERAPIES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; METAANALYSIS C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,OFF DIRECTOR,BETHESDA,MD 20892. RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 12 Z9 12 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 AUG 15 PY 1994 VL 74 IS 4 BP 395 EP 396 DI 10.1016/0002-9149(94)90411-1 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PB381 UT WOS:A1994PB38100017 PM 8059705 ER PT J AU WACHOLDER, S BENICHOU, J HEINEMAN, EF HARTGE, P HOOVER, RN AF WACHOLDER, S BENICHOU, J HEINEMAN, EF HARTGE, P HOOVER, RN TI ATTRIBUTABLE RISK - ADVANTAGES OF A BROAD DEFINITION OF EXPOSURE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE BIAS (EPIDEMIOLOGY); BIOMETRY; CASE-CONTROL STUDIES; EPIDEMIOLOGIC METHODS; OCCUPATIONAL EXPOSURE; ODDS RATIO; SENSITIVITY AND SPECIFICITY; STATISTICS AB Classification of exposure into two levels-one consisting exclusively of unexposed individuals and the other consisting of exposed and perhaps unexposed ones-yields an unbiased estimate of attributable risk when misclassification is nondifferential. The authors advocate, therefore, the use of a broad definition of exposure when estimating attributable risk. Based on this idea, they justify a simple and robust method for estimating the overall attributable risk from several exposures that is based on a division of subjects into two groups, a baseline consisting of those unexposed to all exposures and everyone else. RP WACHOLDER, S (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD, USA. NR 8 TC 98 Z9 99 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1994 VL 140 IS 4 BP 303 EP 309 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC269 UT WOS:A1994PC26900001 PM 8059765 ER PT J AU LUBIN, JH AF LUBIN, JH TI LUNG-CANCER AND EXPOSURE TO RESIDENTIAL RADON SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID URANIUM MINERS; INDOOR RADON; TIN MINERS; STATES; CHINA; WOMEN; RISK; RN; DAUGHTERS RP LUBIN, JH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN,RM 403,6130 EXECUT PLAZA BLVD,ROCKVILLE,MD 20852, USA. NR 36 TC 62 Z9 63 U1 2 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1994 VL 140 IS 4 BP 323 EP 332 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC269 UT WOS:A1994PC26900003 PM 8059767 ER PT J AU OLAH, Z LEHEL, C JAKAB, G ANDERSON, WB AF OLAH, Z LEHEL, C JAKAB, G ANDERSON, WB TI A CLONING AND EPSILON-EPITOPE-TAGGING INSERT FOR THE EXPRESSION OF POLYMERASE CHAIN REACTION-GENERATED CDNA FRAGMENTS IN ESCHERICHIA-COLI AND MAMMALIAN-CELLS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SIGNAL TRANSDUCTION; PROTEIN-KINASE; ONCOGENE; COMPLEX AB An intercompatible gene-tagging insert sequence was designed to conveniently introduce epitope-tagged polypeptides into bacteria and mammalian cells. The presence of rare restriction enzyme sites located between the ATG codon and the sequence encoding the introduced epsilon-tag creates a general cloning site which allows efficient cloning of virtually any desired cDNA fragment produced by the polymerase chain reaction (PCR). The tagging insert sequence encodes a KGF-SYFGEDLMP peptide, derived from the last 12 amino acids of the protein kinase C epsilon gene, to serve as a C-terminal epitope tag of the expressed protein. While the insert can be readily adapted for insertion into any expression vector, this paper details the introduction and characterization of the epsilon-epitope-tagging insert into the bacterial pTrcHis A (epsilon TrcHis A) vector and into the metallothionein promoter-driven eukaryotic (epsilon MTH) expression vector. The expressed epsilon-tagged proteins can be readily detected with a commercially available antibody specific for the epsilon-peptide. Immunoscreening of Escherichia coli colonies transformed with the PCR-generated cDNA inserted into the epsilon TrcHis A vector enables rapid, direct biochemical characterization of the PCR product. The biochemically characterized gene constructs from the epsilon TrcHis A plasmid can be inserted into the epsilon MTH vector by a single subcloning step using the introduced compatible cohesive ends. This epsilon-epitope-tagging insert provides investigators with a versatile, uncomplicated, and reliable method of expressing an epitope-tagged PCR product in the cell type of interest. The epsilon-epitope tagging of the expressed peptide facilitated: (1) immunoscreening of NIH 3T3 transfectants by Western blot analysis for the introduced polypeptide, (2) immunoprecipitation of the overexpressed gene products following metabolic labeling with [S-35]methionine and [P-32]orthophosphate, and (3) subcellular localization of different recombinant proteins by immunocytochemistry. (C) 1994 Academic Press,Inc. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 16 TC 69 Z9 69 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 AUG 15 PY 1994 VL 221 IS 1 BP 94 EP 102 DI 10.1006/abio.1994.1384 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PB292 UT WOS:A1994PB29200014 PM 7527191 ER PT J AU DETTORRE, C LEVINE, RL AF DETTORRE, C LEVINE, RL TI REACTIVITY OF CYSTEINE-67 OF THE HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE - STUDIES ON A PEPTIDE SPANNING RESIDUE-59 TO RESIDUE-75 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS PROTEASE; CYSTEINE RESIDUE REACTIVITY; PROTEIN STRUCTURE AND ELECTROSTATIC INTERACTIONS; PEPTIDE MODELS FOR PROTEIN STRUCTURE ID HIV-1 PROTEASE; VIRAL INFECTIVITY; ASPARTIC PROTEASE; CRYSTAL-STRUCTURE; ION-PAIR; AIDS; TARGET AB The protease encoded by the human immunodeficiency virus-1 (HIV-1) is essential for the processing of viral polyproteins into mature viral proteins. The 99-residue protease from HIV-1 contains two generally conserved cysteine residues, one of which (Cys-67) is located on the solvent-exposed surface. It was shown previously that Cys-67 of the native enzyme reacted with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB, Ellman's reagent) at pH 6.2, causing a reversible inactivation of the protease. However, there was no reaction when the protein was denatured in 6 M guanidine hydrochloride, implying that the native conformation rendered Cys-67 more reactive. To investigate the structural basis of the lowered pK(a) in the native protein, we synthesized a 17-residue peptide matching the sequence of residues 59-75. The reactivity of this synthetic peptide with DTNB mimicked that of the protease, being more reactive in the absence of 6 hi guanidine hydrochloride than in its presence. It was possible that His-69 or Lys-70 could facilitate ionization of the SH group of Cys-67, which is required for reaction with DTNB. Apparently both residues are important, because increased reactivity of the native peptide was eliminated when either His-69 or Lys-70 were changed to Ala. Replacement of His-69 by Glu reversed the reactivity, so that the native peptide was less reactive than that denatured in guanidine hydrochloride. Thus, the reactivity of Cys-67 is modulated by the charges on residues 69 and 70 in the protein. The presence of His-69 and Lys-70 renders the native protease especially susceptible to oxidation and disulfide formation. The resulting reversible inactivation of the protease may be important in the normal regulation of the viral life cycle, a suggestion supported by the strong conservation of the residues in this region. C1 NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 28 TC 8 Z9 8 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 15 PY 1994 VL 313 IS 1 BP 71 EP 76 DI 10.1006/abbi.1994.1360 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PB624 UT WOS:A1994PB62400011 PM 8053689 ER PT J AU IRANI, K HERZLINGER, S FINKEL, T AF IRANI, K HERZLINGER, S FINKEL, T TI RAS PROTEINS REGULATE MULTIPLE MITOGENIC PATHWAYS IN A10 VASCULAR SMOOTH-MUSCLE CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NIH 3T3 CELLS; GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; REQUIREMENT; FIBROBLASTS; ACTIVATION; MIGRATION; MUTATION; P21(RAS) AB We examined the role of ras proteins in mitogenesis and proliferation of A10 smooth muscle cells. An assay was developed in which a dominant negative ras gene could be transiently expressed in vascular smooth muscle cells. As opposed to cells transfected with a control plasmid, those transfected with a dominant negative ras expression plasmid exhibited a decrease in thymidine uptake in response to serum, platelet-derived growth factor, epidermal growth factor, fibroblast growth factor and thrombin stimulation. In addition, expression of dominant negative ras blocked smooth muscle cell proliferation as assessed by the number of surviving colonies after transfection and neomycin selection. Our data is the first to show that ras is essential for smooth muscle cell proliferation and is a mediator in multiple smooth muscle cell mitogenic signalling pathways. (C) 1994 Academic Press, Inc. RP IRANI, K (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 19 TC 26 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 15 PY 1994 VL 202 IS 3 BP 1252 EP 1258 DI 10.1006/bbrc.1994.2065 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PB553 UT WOS:A1994PB55300009 PM 8060300 ER PT J AU CHUANG, LF CHUANG, TK KILLAM, KP CHUANG, AJ KUNG, H YU, L CHUANG, RY AF CHUANG, LF CHUANG, TK KILLAM, KP CHUANG, AJ KUNG, H YU, L CHUANG, RY TI DELTA-OPIOID RECEPTOR GENE-EXPRESSION IN LYMPHOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PERIPHERAL-BLOOD; OPIATE RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; MORPHINE; CELLS; REPLICATION; INVIVO; BRAIN AB Previous studies have shown that morphine stimulates simian immunodeficiency virus (SIV) replication in SIV-infected human CEM x174 cells as well as in monkey lymphocytes through a mechanism of delaying the lysis of infected cells (Biochem. Biophys. Res. Commun. 195:1165-1173, 1993). The present study describes the identification of brain-like opioid receptor sequences in RNA transcripts of both CEM x174 cells and monkey lymphocytes. Study of the gene sequence of a lymphocyte opioid receptor encompassing the third transmembrane domain and the third cytoplasmic loop indicates a 96% homology in amino acid composition to the delta opioid receptor in brain cells. Expression of such an opioid receptor sequence in,lymphocytic cells is constitutive, since it could be detected in both saline-treated and morphine-treated monkeys as well as in morphine-treated monkeys after detoxification. (C) 1994 Academic Press, Inc. C1 UNIV CALIF DAVIS,DEPT MED PHARMACOL & TOXICOL,DAVIS,CA 95616. NCI,FREDERICK,MD 21701. INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. FU NIDA NIH HHS [DA05901] NR 29 TC 118 Z9 121 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 AUG 15 PY 1994 VL 202 IS 3 BP 1291 EP 1299 DI 10.1006/bbrc.1994.2071 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PB553 UT WOS:A1994PB55300015 PM 8060306 ER PT J AU NISHIMURA, H SIMPSON, IA AF NISHIMURA, H SIMPSON, IA TI STAUROSPORINE INHIBITS PHORBOL 12-MYRISTATE 13-ACETATE-STIMULATED AND INSULIN-STIMULATED TRANSLOCATION OF GLUT1 AND GLUT4 GLUCOSE TRANSPORTERS IN RAT ADIPOSE-CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; 3T3-L1 ADIPOCYTES; PHENYLARSINE OXIDE; HEXOSE-TRANSPORT; INCREASES MEMBRANE; POTENT INHIBITOR; SKELETAL-MUSCLE; BC3H-1 MYOCYTES; TYROSINE KINASE; FAT-CELLS AB Staurosporine, a widely used protein kinase C inhibitor, completely inhibited both phorbol 12-myristate 13-acetate (PMA)- and insulin-stimulated glucose transport activity in isolated rat adipocytes. The inhibition was non-competitive and was attributed to a blockade of the PMA- and insulin-induced translocation of both GLUT1 and GLUT4 glucose transporters. The PMA-stimulated glucose transport activity was more sensitive to inhibition by staurosporine than was insulin-stimulated transport activity (PMA, IC50 = 1.1 +/- 0.1 mu M; insulin, IC50 = 6.4 +/- 0.7 mu M; P < 0.05, n = 3). At 1 mu M staurosporine the insulin-sensitivity was decreased, i.e. EC(50) increased from 0.12 nM to 5.4 nM, but the maximum response to insulin and the time course for stimulation were unaffected. At 6 mu M staurosporine the insulin-sensitivity was further decreased, the maximal stimulation was decreased by 25%, and the apparent half-time for stimulation was extended from 2.5 min in control cells to 9.4 min. Staurosporine (30 mu M) was able to block insulin's ability to stimulate glucose transport, whether added before or after insulin, by a mechanism that did not alter the rate of GLUT4 internalization. In intact adipose cells, staurosporine (30 mu M) induced a slight (30%) decrease in the maximal insulin-induced receptor autophosphorylation and a similar decrease in the tyrosine phosphorylation of pp60 and pp160 (insulin-receptor substrate-1: 'IRS-1'), but was without effect on insulin binding to its receptor. Conversely, staurosporine induced a concentration-dependent inhibition of the constitutively tyrosine-phosphorylated (pp120) protein and of an insulin-stimulated protein pp53 in the cytosol. The locus of staurosporine's action appears to be distal from the initial insulin-receptor signalling, at a step that regulates the specific translocation of the glucose transporters to the plasma membranes. C1 NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NR 46 TC 63 Z9 63 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 15 PY 1994 VL 302 BP 271 EP 277 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC828 UT WOS:A1994PC82800038 PM 8068015 ER PT J AU EYSTER, ME FRIED, MW DIBISCEGLIE, AM GOEDERT, JJ AF EYSTER, ME FRIED, MW DIBISCEGLIE, AM GOEDERT, JJ TI INCREASING HEPATITIS-C VIRUS-RNA LEVELS IN HEMOPHILIACS - RELATIONSHIP TO HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AND LIVER-DISEASE SO BLOOD LA English DT Note ID NATURAL-HISTORY; MULTITRANSFUSED HEMOPHILIACS; HCV; PREVALENCE; ANTIBODY; SUBSETS; THERAPY C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. RP EYSTER, ME (reprint author), PENN STATE UNIV,COLL MED,DEPT MED,DIV HEMATOL,POB 850,HERSHEY,PA 17033, USA. FU NCI NIH HHS [N01-CP-33002-21, N01-CP-85649] NR 22 TC 321 Z9 327 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1994 VL 84 IS 4 BP 1020 EP 1023 PG 4 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200003 PM 8049420 ER PT J AU WRIGHT, DG KENNEY, RF OETTE, DH LARUSSA, VF BOXER, LA MALECH, HL AF WRIGHT, DG KENNEY, RF OETTE, DH LARUSSA, VF BOXER, LA MALECH, HL TI CONTRASTING EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (CSF) AND GRANULOCYTE CSF TREATMENT ON THE CYCLING OF BLOOD-ELEMENTS IN CHILDHOOD-ONSET CYCLIC NEUTROPENIA SO BLOOD LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; GM-CSF; DRUG-THERAPY; GRANULOPOIESIS C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. SANDOZ INC,RES INST,E HANOVER,NJ 07936. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. UNIV MICHIGAN,CS MOTT CHILDRENS HOSP,MED CTR,PEDIAT HEMATOL ONCOL SECT,ANN ARBOR,MI 48109. BOSTON CITY HOSP,WILLIAM CASTLE HEMATOL RES LAB,BOSTON,MA 02118. RP WRIGHT, DG (reprint author), BOSTON UNIV,SCH MED,BCH THORNDIKE 2,818 HARRISON AVE,BOSTON,MA 02118, USA. FU NCRR NIH HHS [MO1RR0042]; NIAID NIH HHS [R01AI20065] NR 26 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1994 VL 84 IS 4 BP 1257 EP 1267 PG 11 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200034 PM 7519479 ER PT J AU CUNNINGHAM, JM PURUCKER, ME JANE, SM SAFER, B VANIN, EF NEY, PA LOWREY, CH NIENHUIS, AW AF CUNNINGHAM, JM PURUCKER, ME JANE, SM SAFER, B VANIN, EF NEY, PA LOWREY, CH NIENHUIS, AW TI THE REGULATORY ELEMENT 3' TO THE (A)GAMMA-GLOBIN GENE BINDS TO THE NUCLEAR MATRIX AND INTERACTS WITH SPECIAL A-T-RICH BINDING-PROTEIN-1 (SATB1), AN SAR/MAR-ASSOCIATING REGION DNA-BINDING PROTEIN SO BLOOD LA English DT Article ID GAMMA-GLOBIN GENE; TRANSGENIC MICE; RNA-POLYMERASE; EXPRESSION; PROMOTER; SEQUENCES; LOCUS; IDENTIFICATION; ENHANCER; SITES C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NHLBI,MOLEC HEMATOL LAB,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD. NR 48 TC 54 Z9 54 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1994 VL 84 IS 4 BP 1298 EP 1308 PG 11 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200039 PM 8049444 ER PT J AU ANASETTI, C HANSEN, JA WALDMANN, TA APPELBAUM, FR DAVIS, J DEEG, HJ DONEY, K MARTIN, PJ NASH, R STORB, R SULLIVAN, KM WITHERSPOON, RP BINGER, MH CHIZZONITE, R HAKIMI, J MOULD, D SATOH, H LIGHT, SE AF ANASETTI, C HANSEN, JA WALDMANN, TA APPELBAUM, FR DAVIS, J DEEG, HJ DONEY, K MARTIN, PJ NASH, R STORB, R SULLIVAN, KM WITHERSPOON, RP BINGER, MH CHIZZONITE, R HAKIMI, J MOULD, D SATOH, H LIGHT, SE TI TREATMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE WITH HUMANIZED ANTI-TAC - AN ANTIBODY THAT BINDS TO THE INTERLEUKIN-2 RECEPTOR SO BLOOD LA English DT Article ID MONOCLONAL-ANTIBODY; MARROW TRANSPLANTATION; IL-2 RECEPTOR; RETROSPECTIVE ANALYSIS; ACUTE GVHD; PHASE-I; THERAPY; PHARMACOKINETICS; CELLS; METHOTREXATE C1 NIH,METAB BRANCH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. RP ANASETTI, C (reprint author), UNIV WASHINGTON,FRED HUTCHINSON CANC RES CTR,DEPT MED,DIV CLIN RES,DIV ONCOL,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. FU NCI NIH HHS [CA 18029, CA 18221]; NHLBI NIH HHS [HL36444] NR 35 TC 147 Z9 150 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1994 VL 84 IS 4 BP 1320 EP 1327 PG 8 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200042 PM 8049447 ER PT J AU TIBERGHIEN, P REYNOLDS, CW KELLER, J SPENCE, S DESCHASEAUX, M CERTOUX, JM CONTASSOT, E MURPHY, WJ LYONS, R CHIANG, YW HERVE, P LONGO, DL RUSCETTI, FW AF TIBERGHIEN, P REYNOLDS, CW KELLER, J SPENCE, S DESCHASEAUX, M CERTOUX, JM CONTASSOT, E MURPHY, WJ LYONS, R CHIANG, YW HERVE, P LONGO, DL RUSCETTI, FW TI GANCICLOVIR TREATMENT OF HERPES-SIMPLEX THYMIDINE KINASE-TRANSDUCED PRIMARY T-LYMPHOCYTES - AN APPROACH FOR SPECIFIC IN-VIVO DONOR T-CELL DEPLETION AFTER BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; TUMOR-INFILTRATING LYMPHOCYTES; HLA-IDENTICAL SIBLINGS; ACUTE GRAFT; GENE-TRANSFER; ADOPTIVE IMMUNOTHERAPY; BRAIN-TUMORS; PHASE-I; LEUKEMIA; ANTIBODY C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. GENET THERAPY INC,GAITHERSBURG,MD. RP TIBERGHIEN, P (reprint author), CTR REG TRANSFUS SANGUINE,HISTOCOMPATIBIL & IMMUNOMOLEC THERAPEUT LAB,BUD FLEMING,F-25000 BESANCON,FRANCE. NR 38 TC 189 Z9 191 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1994 VL 84 IS 4 BP 1333 EP 1341 PG 9 WC Hematology SC Hematology GA PC402 UT WOS:A1994PC40200044 PM 8049449 ER PT J AU SHOU, MS KORZEKWA, KR KRAUSZ, KW CRESPI, CL GONZALEZ, FJ GELBOIN, HV AF SHOU, MS KORZEKWA, KR KRAUSZ, KW CRESPI, CL GONZALEZ, FJ GELBOIN, HV TI REGIOSELECTIVE AND STEREOSELECTIVE METABOLISM OF PHENANTHRENE BY 12 CDNA-EXPRESSED HUMAN, RODENT, AND RABBIT CYTOCHROMES P-450 SO CANCER LETTERS LA English DT Article DE PHENANTHRENE METABOLISM; HUMAN; CYTOCHROME P-450; CDNA EXPRESSION; HIGH-PRESSURE LIQUID CHROMATOGRAPHY ID POLYCYCLIC AROMATIC-HYDROCARBONS; TUMOR-INITIATING ACTIVITY; STEREOSELECTIVE METABOLISM; MONOOXYGENASE INDUCERS; LIVER MICROSOMES; MUTAGENICITY; CHRYSENE; CELLS; CARCINOGENESIS; TUMORIGENICITY AB The regio- and stereoselective metabolism of phenanthrene (PA) by seven cDNA-expressed human and five rodent and rabbit cytochromes P-450 has been examined using reverse-phase and chiral stationary phase high-pressure liquid chromatography (HPLC). Turnover numbers ranged from 0.2 to 55 nmol/min per nmol. Using vaccinia virus expression of P-450 enzymes in Hep G2 cells, m1A1 and m1A2 were found to be the most active P-450s. Of the human P-450s, 1A2 and 2B6 have the highest activity and 2C9 has moderate activity. Using cytochrome P-450s expressed in a lymphoblastoid cell line in presence of epoxide hydrolase (EH), human 1A1 had approximately twice the activity of human 1A2. Regioselectivities for PA metabolism were found to be both isozyme and species-dependent. Stereochemical analysis revealed that the P-450s 1A1, m1A1, m1A2, r2A1, r2B1, PB- and 3MC-treated rat liver microsomes preferentially formed 3R,4R-diol enantiomer (88-97%), whereas rabbit 4B formed the 3S,4S-diol enantiomer (72%). Eleven P-450s, 3MC and PB microsomes preferentially formed 1R,2R-diol enantiomer (80-96%). This is the same stereochemistry as the precursors to some diol epoxides that are potent carcinogens. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. GENTEST CORP,WOBURN,MA 01801. NR 32 TC 59 Z9 61 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 15 PY 1994 VL 83 IS 1-2 BP 305 EP 313 DI 10.1016/0304-3835(94)90334-4 PG 9 WC Oncology SC Oncology GA PD151 UT WOS:A1994PD15100045 PM 8062229 ER PT J AU FUJINO, T RISINGER, JI COLLINS, NK LIU, FS NISHII, H TAKAHASHI, H WESTPHAL, EM BARRETT, JC SASAKI, H KOHLER, MF BERCHUCK, A BOYD, J AF FUJINO, T RISINGER, JI COLLINS, NK LIU, FS NISHII, H TAKAHASHI, H WESTPHAL, EM BARRETT, JC SASAKI, H KOHLER, MF BERCHUCK, A BOYD, J TI ALLELOTYPE OF ENDOMETRIAL CARCINOMA SO CANCER RESEARCH LA English DT Note ID TUMOR SUPPRESSOR GENES; HUMAN PROSTATE-CANCER; K-RAS ACTIVATION; ALLELIC LOSS; COLORECTAL CARCINOMAS; OVARIAN-CANCER; FREQUENT LOSS; HETEROZYGOSITY; MUTATIONS; DELETION AB An allelotype analysis of endometrial carcinoma was undertaken to identify chromosomal loci that are relevant to this tumor type. A total of 70 highly polymorphic microsatellite markers, distributed among all nonacrocentric chromosome arms, were examined for evidence of loss of heterozygosity or allelic imbalance in DNA samples from matched normal and tumor tissues. An average of 21 informative tumor cases were obtained for each marker. Allelic deletions or imbalance were observed on 31 of 41 chromosome arms with no marker showing an allelic loss ratio of greater than 33%. Those chromosome arms most frequently involved were 3p, 8p, 9p 14q, 16q, and 18q. There was a strong correlation between loss of heterozygosity on chromosome 14q and death from disease. These data indicate that the molecular genetic character of endometrial carcinoma is complex and that a relatively large number of different chromosomal loci are likely to play a role in the etiology and progression of this tumor type. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. JIKEI UNIV,SCH MED,DEPT OBSTET & GYNECOL,TOKYO 105,JAPAN. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 48 TC 97 Z9 99 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1994 VL 54 IS 16 BP 4294 EP 4298 PG 5 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200011 PM 8044774 ER PT J AU REIFENBERGER, G REIFENBERGER, J ICHIMURA, K MELTZER, PS COLLINS, VP AF REIFENBERGER, G REIFENBERGER, J ICHIMURA, K MELTZER, PS COLLINS, VP TI AMPLIFICATION OF MULTIPLE GENES FROM CHROMOSOMAL REGION 12Q13-14 IN HUMAN-MALIGNANT GLIOMAS - PRELIMINARY MAPPING OF THE AMPLICONS SHOWS PREFERENTIAL INVOLVEMENT OF CDK4, SAS, AND MDM2 SO CANCER RESEARCH LA English DT Note ID CYCLIN-DEPENDENT KINASES; HUMAN MAMMARY-TUMORS; HUMAN SARCOMAS; MYXOID LIPOSARCOMA; PHYSICAL MAP; N-MYC; GLI; PROTEIN; OVEREXPRESSION; FUSION AB We have investigated 234 tumors of the central nervous system for amplification of 9 different loci from 12q13 14 and report that about 15% of the anaplastic astrocytomas and glioblastomas show amplification at this chromosomal region. The genes most frequently amplified were CDK4 and SAS (18 of 19 cases). MDM2 was coamplified with CDK4 and SAS in 11 tumors while one glioblastoma showed only MDM2 amplification. Some amplicons additionally included GADD153 (9 cases), GLI (6 cases), A2MR (3 cases), and the anonymous locus D12S8 (2 cases). Either MDM2 or CDK4 and SAS showed the highest amplification level in each individual amplicon and amplification of these genes was consistently accompanied by strong overexpression. Our results thus suggest CDK4, SAS, and MDM2 as main targets for the amplification; however, the possibility exists that all amplicons share a common amplified region between MDM2 and CDK4/SAS which might contain one or more as yet unidentified genes. C1 KAROLINSKA HOSP,DEPT PATHOL,S-17176 STOCKHOLM,SWEDEN. SAHLGRENS UNIV HOSP,DEPT PATHOL,S-41345 GOTHENBURG,SWEDEN. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV DUSSELDORF,DEPT NEUROPATHOL,D-40225 DUSSELDORF,GERMANY. LUDWIG INST CANC RES,STOCKHOLM BRANCH,S-17176 STOCKHOLM,SWEDEN. NR 34 TC 264 Z9 267 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 AUG 15 PY 1994 VL 54 IS 16 BP 4299 EP 4303 PG 5 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200012 PM 8044775 ER PT J AU KOI, M UMAR, A CHAUHAN, DP CHERIAN, SP CARETHERS, JM KUNKEL, TA BOLAND, CR AF KOI, M UMAR, A CHAUHAN, DP CHERIAN, SP CARETHERS, JM KUNKEL, TA BOLAND, CR TI HUMAN-CHROMOSOME-3 CORRECTS MISMATCH REPAIR DEFICIENCY AND MICROSATELLITE INSTABILITY AND REDUCES N-METHYL-N'-NITRO-N-NITROSOGUANIDINE TOLERANCE IN COLON-TUMOR CELLS WITH HOMOZYGOUS HMLH1 MUTATION SO CANCER RESEARCH LA English DT Note ID GENETIC INSTABILITY; COLORECTAL-CANCER; DNA; POLYMORPHISMS; EXTRACTS; HOMOLOG; BINDING; LINE AB The human colon tumor cell line HCT 116 is known to have a homozygous mutation in the mismatch repair gene hMLH1 on human chromosome 3, to exhibit microsatellite instability, and to be defective in mismatch repair. In order to determine whether the introduction of a normal copy of hMLH1 gene restores mismatch repair activity and corrects microsatellite instability, a single human chromosome 3 from normal fibroblasts was transferred to HCT 116 cells via microcell fusion. As a control, human chromosome 2 was also transferred to HCT 116 cells. Two HCT 116 microcell hybrid clones that received a single copy of chromosome 2 (HCT 116+ch2) and two that received a single copy of chromosome 3 (HCT 116+ch3) were isolated and characterized. A G G mismatch in MW-derived heteroduplex DNA was efficiently repaired in cell extracts from HCT 116+ch3 cells, but not in those of parent HCT 116 cells or HCT 116+ch2 cells. Microsatellite alterations at the D5S107 locus containing CA repeats were seen in 8 of 80 subclones from HCT 116 cells, and in 13 of 150 subclones from HCT 116+ch2 cells. In contrast, none of the 225 subclones derived from mismatch repair-proficient HCT 116+ch3 cells showed alterations in the microsatellite at the same locus. The effect of introducing chromosome 3 on the sensitivity of HCT 116 cells to N-methyl-N' nitro-N nitrosoguanidine (MNNG) was examined, since enhanced tolerance to MNNG is accompanied by loss of mismatch repair activity in several cell lines. Within 3 days after treatment with 5 mu 3 MNNG, HCT 116+ch3 cells became morphologically flat and stopped growing. Their colony-forming ability, determined 10 days after treatment, was reduced 200-fold when compared to MNNG-treated parental HCT 116 and HCT 116+ch2 cells. These results support the hypothesis that mutations in both alleles of the hMLH1 gene are necessary for the manifestation of defective mismatch repair and microsatellite instability and for enhanced MNNG tolerance. The results also suggest that the mismatch repair system contributes to the process that causes growth arrest in response to DNA damage by alkylating agents. C1 UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,DIV GASTROENTEROL,ANN ARBOR,MI 48109. VET ADM MED CTR,GASTROENTEROL SECT,ANN ARBOR,MI 48105. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 FU NCI NIH HHS [CA39233, CA46592-06]; NIDDK NIH HHS [P30 DK34933] NR 31 TC 448 Z9 451 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 AUG 15 PY 1994 VL 54 IS 16 BP 4308 EP 4312 PG 5 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200014 PM 8044777 ER PT J AU HARTMANN, F HORAK, EM GARMESTANI, K WU, CC BRECHBIEL, MW KOZAK, RW TSO, J KOSTEINY, SA GANSOW, OA NELSON, DL WALDMANN, TA AF HARTMANN, F HORAK, EM GARMESTANI, K WU, CC BRECHBIEL, MW KOZAK, RW TSO, J KOSTEINY, SA GANSOW, OA NELSON, DL WALDMANN, TA TI RADIOIMMUNOTHERAPY OF NUDE-MICE BEARING A HUMAN INTERLEUKIN-2 RECEPTOR ALPHA-EXPRESSING LYMPHOMA UTILIZING THE ALPHA-EMITTING RADIONUCLIDE-CONJUGATED MONOCLONAL-ANTIBODY BI-212-ANTI-TAC SO CANCER RESEARCH LA English DT Article ID BETA-CHAIN; TAC; THERAPY; CELLS; IMMUNOTHERAPY; ANTIFERRITIN; LEUKEMIA; CANCER; TARGET; BI-212 AB The efficacy, specificity, and toxicity of bismuth (Bi-212) alpha particle-mediated radioimmunotherapy was evaluated in nude mice bearing a murine lymphoma transfected with the human CD25 [human Tac; interleukin 2 receptor alpha (IL-2R alpha)] gene, The therapeutic agent used was the tumor-specific humanized monoclonal antibody anti-Tac conjugated to Bi-212. The human IL-2R alpha-expressing cell line was produced by transfecting the gene encoding human Tac into the murine plasmacytoma cell line SP2/0. The resulting cell line, SP2/Tac, expressed approximately 18,000 human IL-2R alpha molecules/cell. Following s.c. or i.p. injection of 2 x 10(6) SP2/Tac cells into nude mice, rapidly growing tumors developed in all animals after a mean of 10 and 13 days, respectively. The bifunctional chelate cyclohexyldiethylenetriaminepentaacetic acid was used to couple Bi-212 to the humanized anti-Tac monoclonal antibody. This immunoconjugate was shown to be stable in vivo. Specifically, in pharmacokinetic studies in nude mice, the blood clearance patterns of i.v. administered Bi-205/206-anti-Tac and coinjected I-125-anti-Tac were comparable. The toxicity and therapeutic efficacy of Bi-212-anti-Tac were evaluated in nude mouse ascites or solid tumor models wherein SP2/Tac cells were administered either i.p. or s.c., respectively. The i.p. administration of Bi-212-anti-Tac, 3 days following i.p. tumor inoculation, led to a dose-dependent, significant prolongation of tumor-free survival. Doses of 150 or 200 mu Ci prevented tumor occurrence in 75% (95% confidence interval, 41-93%) of the animals. In the second model, i.v. treatment with Bi-212-anti-Tac 3 days following s.c. tumor inoculation also resulted in a prolongation of the period before tumor development. However, prevention of tumor occurrence decreased to 30% (95% confidence interval, 11-60%). In both the i.p. and s.c. tumor trials, Bi-212-anti-Tac was significantly more effective for i.p. (P2 = 0.0128 50/100 mu Ci Bi-212-anti-Tac versus 50/100 mu Ci Mik beta; P2 = 0.0142 150/200 mu Ci anti-Tac versus 150/200 mu Ci Mik beta) and for s.c. tumors (P2 = 0.0018 100 mu Ci anti-Tac versus 100 mu Ci Mik beta; P2 = 0.0042 200 mu Ci anti-Tac versus 200 mu Ci Mik beta 1) than the control antibody Mik beta 1 coupled to Bi-212 at comparable dose levels. In contrast to the efficacy observed in the adjuvant setting, therapy of large, established s.c. SP-2/ Tac-expressing tumors with i.v. administered Bi-212-anti-Tac (at doses up to 200 mu Ci/animal) failed to induce tumor regression. Pharmacokinetic and tissue distribution studies of radiolabeled anti-Tac in this particular therapeutic situation provided an explanation for this observation. Only 5-6% of the injected dose of radiolabeled antibody was present per g of tumor at 2 h following injection at a time when 75% of the administered Bi-212 radioactivity had decayed. Furthermore, at this time point, there was no greater uptake of Bi-anti-Tac into Tac-expressing tumors than was observed with Tac-nonexpressing variants of SP2/0. Finally, the specific antibody Bi-212/206-anti-Tac was not enriched in the tumor when compared to the irrelevant monoclonal antibody Bi-205/206-Mik beta 1. Although specific enrichment of radiolabeled Bi-anti-Tac was not seen at 2 h, such enrichment in the tumor was observed at 5 and 24 h postinjection with up to 15.6% injected dose present per g of tumor. The dose limiting acute toxicity following i.v. administration of Bi-212 anti-Tac was bone marrow suppression, which was observed at doses above 200 mu Ci. In summary, Bi-212-anti-Tac as a complete antibody may be of only limited value in the therapy of bulky solid tumors due to the short physical half-life of Bi-212 and the time required to achieve a useful tumor:normal tissue ratio of the radionuclide following administration of the radiolabeled antibody. However, this radionuclide may be useful in select situations such as adjuvant or intracavitary therapy, strategies that target the vascular endothelial cells of tumors, or in the treatment of leukemias. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,INORGAN & RADIOIMMUNE CHEM SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,BETHESDA,MD 20892. PROT DESIGN LABS INC,MT VIEW,CA 94043. NR 41 TC 63 Z9 65 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 AUG 15 PY 1994 VL 54 IS 16 BP 4362 EP 4370 PG 9 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200022 PM 8044783 ER PT J AU FLESSNER, MF DEDRICK, RL AF FLESSNER, MF DEDRICK, RL TI MONOCLONAL-ANTIBODY DELIVERY TO INTRAPERITONEAL TUMORS IN RATS - EFFECTS OF ROUTE OF ADMINISTRATION AND INTRAPERITONEAL SOLUTION OSMOLALITY SO CANCER RESEARCH LA English DT Article ID BIDIRECTIONAL PERITONEAL TRANSPORT; QUANTITATIVE AUTORADIOGRAPHY; IMMUNOGLOBULIN; ABSORPTION; TISSUE; CARCINOMA; PRESSURE; DIALYSIS; PROTEIN AB Monoclonal antibody (MAb) transport in peritoneal tissue is dominated by convection, which is dependent on the net driving force of i.p. hydrostatic and osmotic pressure. To test the hypothesis that the i.p. osmolality has significant effects on IgG delivery to the tumor during the acute period after injection, solid tumors (FEMX-II) were transplanted into the anterior abdominal wall of nude rats. The wall is subject to well-defined pressure forces from the solution in the cavity. MAb 96.5, which specifically binds to FEMX-II cells, was simultaneously injected i.v. (In-111-MAb 96.5 in Krebs Ringer solution) and i.p. (I-125-MAb 96.5 in dialysis solution). Intraperitoneal hydrostatic pressure was held constant, and the osmolality of the i.p. solution was varied between isotonic and hypertonic (with the addition of 4% mannitol to an isotonic salt solution) in order to vary the direction of net convection. Plasma and peritoneal concentrations of both isotopes were measured at intervals over 200 min, and tissue concentration profiles in tumor and adjacent normal tissue were determined by dual-label quantitative autoradiography at 200 min. After i.v. administration, profiles were relatively flat and little affected by i.p. osmolality. After i.p. injection, profiles demonstrated steep concentration decreases from the peritoneal surface into the tissue for several hundred mu m. Despite the change from the condition of water absorption from the cavity into the body (isotonic solution) to one of net volume gain by the cavity (hypertonic solution), tumor profiles were affected by i.p. osmolality only near the surface. Specific binding properties of the tumor were determined for the tumors studied and were consistent with high surface concentrations relative to normal tissue. Variation of the i.p. solution osmolality by changes in concentration of small molecules exerts only minor effects on the short-term MAb delivery from either systemic or regional administration to a target tumor in the anterior abdominal wall in the rat. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 18 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1994 VL 54 IS 16 BP 4376 EP 4384 PG 9 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200024 PM 8044785 ER PT J AU FASSANITO, MA LOFTUS, D DELEO, RM LAW, LW APPELLA, E DELEO, AB AF FASSANITO, MA LOFTUS, D DELEO, RM LAW, LW APPELLA, E DELEO, AB TI CHARACTERIZATION OF CLONED CLASS-I MHC-RESTRICTED, CD8+ ANTI-METH-A CYTOTOXIC T-LYMPHOCYTES - RECOGNITION OF AN EPITOPE DERIVED FROM THE METH-A GP110 TUMOR REJECTION ANTIGEN SO CANCER RESEARCH LA English DT Article ID CHEMICALLY-INDUCED SARCOMAS; INFILTRATING LYMPHOCYTES; UNIQUE ANTIGEN; CELLS; EXPRESSION; PEPTIDES; PROTEIN; INDUCTION; IMMUNITY; MUTANT AB Meth A gp110 has been tentatively identified as a tumor rejection antigen. Following isolation of a class I major histocompatibility complex (MHC)-restricted, CD8(+) anti-Meth A cytotoxic T-lymphocyte (CTL), we sought to determine whether the determinant recognized by this CTL was: (a) functional in tumor rejection of Meth A sarcoma; and (b) derived from Meth A gp110. Initially, we isolated an anti-Meth A CTL-resistant variant of Meth A sarcoma, Meth A4R, by immunoselection. The results of the subsequent analysis of Meth A4R cells showed the CTL-defined determinant as having a functional role in transplantation rejection of Meth A sarcoma. Walker et al. (Proc. Natl. Acad. Sci. USA, 89: 7915-7918, 1993) showed that the cationic lipid, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium-methyl sulfate, mediated delivery of a recombinant glycoprotein into the cytosol of target cells, making it available for processing and presentation by class I MHC molecules. As a result, the cells were sensitized for cytolysis by a class I MHC-restricted CD8+ CTL, which recognized an epitope expressed by the glycoprotein. In a similar manner, we treated the SV40-transformed BALB/c cell line, SVBalb, which is relatively insensitive to cytolysis by the anti-Meth A CTL, with Meth A gp110 and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate. The sensitivities of the treated cells and control cell lines to the anti-Meth A CTL were then examined. The results of these experiments permit us to conclude that the determinant recognized by the anti Meth A CTL line is derived from Meth A gp110. C1 UNIV PITTSBURGH,SCH MED,PITTSBURGH CANC INST,DIV BASIC SCI,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA 15213. NCI,BETHESDA,MD 20892. NR 38 TC 9 Z9 9 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1994 VL 54 IS 16 BP 4424 EP 4429 PG 6 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200031 PM 7519121 ER PT J AU TENDLER, CL BURTON, JD JAFFE, J DANIELPOUR, D CHARLEY, M MCCOY, JP PITTELKOW, MR WALDMANN, TA AF TENDLER, CL BURTON, JD JAFFE, J DANIELPOUR, D CHARLEY, M MCCOY, JP PITTELKOW, MR WALDMANN, TA TI ABNORMAL CYTOKINE EXPRESSION IN SEZARY AND ADULT T-CELL LEUKEMIA-CELLS CORRELATES WITH THE FUNCTIONAL DIVERSITY BETWEEN THESE T-CELL MALIGNANCIES SO CANCER RESEARCH LA English DT Article ID GROWTH FACTOR-BETA; I-ASSOCIATED MYELOPATHY; NATURAL-KILLER CELLS; MYCOSIS-FUNGOIDES; IFN-GAMMA; LYMPHOMA; IL-4; PROLIFERATION; LYMPHOCYTES; TRANSACTIVATION AB The Sezary syndrome (SzS) and adult T-cell leukemia (ATL) are malignant proliferations of mature T-lymphocytes that possess distinct functions. Sezary cells function as helper cells, whereas ATL cells are usually suppressor effecters. Although phenotypically similar (CD4+/CD7-/CD8-), these functional differences between the T-cell lymphoproliferative disorders suggest different patterns of cytokine expression. We wished to delineate the cytokine mechanisms potentially underlying the diverse functional characteristics of SzS and ATL. Therefore, we analyzed the expression of interleukins (IL) 2, 4, and 5, gamma-interferon, and transforming growth factor beta(1) in the highly purified leukemic T-cells from 5 SzS and 5 ATL patients. Decreased mRNA and protein levels of IL-2, gamma-interferon, and IL-5 were detected in mitogen-stimulated ATL and SzS cells when compared to similarly cultured normal CD4+ cells. In contrast, IL-4 production was markedly up-regulated in the leukemic cells of 4/5 SzS patients as compared to ATL and normal controls. Finally, fresh ATL cells secreted higher levels of transforming growth factor beta(1) into the culture medium than the malignant T-cells from SzS patients. Collectively these results suggest that, similar to the murine CD4-expressing T-cell subsets Th1 and Th2, different cytokine profiles exist in a human population of CD4+ T-cells. Moreover, the distinct patterns of IL-4 and transforming growth factor beta(1) expression by SzS and ATL cells, respectively, are most consistent with the functional differences (i.e., helper versus suppressor activity) between these T cell malignancies and thus may play important roles in the pathogenesis of the paraneoplastic features associated with these two leukemias. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. HAHNEMANN UNIV,DIV ALLERGY & PULM MED,PHILADELPHIA,PA 19102. UNIV PITTSBURGH,SCH MED,DEPT DERMATOL,PITTSBURGH,PA 15260. MAYO CLIN & MAYO FDN,DEPT DERMATOL,ROCHESTER,MN 55905. RP TENDLER, CL (reprint author), MT SINAI MED CTR,MT SINAI SCH MED,DIV PEDIAT ONCOL,BOX 1208,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. FU NICHD NIH HHS [NICHD 5P30 HD28822] NR 33 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1994 VL 54 IS 16 BP 4430 EP 4435 PG 6 WC Oncology SC Oncology GA PB502 UT WOS:A1994PB50200032 PM 7913876 ER PT J AU KEARSE, KP WILLIAMS, DB SINGER, A AF KEARSE, KP WILLIAMS, DB SINGER, A TI PERSISTENCE OF GLUCOSE RESIDUES ON CORE OLIGOSACCHARIDES PREVENTS ASSOCIATION OF TCR-ALPHA AND TCR-BETA PROTEINS WITH CALNEXIN AND RESULTS SPECIFICALLY IN ACCELERATED DEGRADATION OF NASCENT TCR-ALPHA PROTEINS WITHIN THE ENDOPLASMIC-RETICULUM SO EMBO JOURNAL LA English DT Article DE CALNEXIN; ENDOPLASMIC RETICULUM; GLUCOSE TRIMMING; T-CELL RECEPTOR ID CELL ANTIGEN RECEPTOR; PRE-GOLGI COMPARTMENT; T-CELL; MONOCLONAL-ANTIBODY; RAPID DEGRADATION; COMPLEX; CHAINS; IDENTIFICATION; BIOSYNTHESIS; RECOGNITION AB The alpha beta T-cell antigen receptor (TCR) is a multisubunit transmembrane complex composed of at least six different proteins (alpha, beta, gamma, delta, epsilon and zeta) that are assembled in the endoplasmic reticulum (ER). In this report we have examined the role of oligosaccharide processing on survival and assembly of nascent TCR proteins within the ER and their associations with molecular chaperone proteins important in TCR assembly. We found that treatment of BW5147 T cells with the glucosidase inhibitor castanospermine resulted in markedly accelerated degradation of nascent TCR alpha proteins with a half-life of similar to 20 min. Accelerated degradation was unique to TCR alpha proteins, as the stability of nascent TCR beta and CD3 gamma,epsilon chains was unaltered. Consistent with a requirement for glucose (Glc) trimming for survival of nascent TCR alpha proteins within the ER, we found that newly synthesized TCR alpha chains were innately unstable in the glucosidase II-deficient BW5147 mutant cell line PHAR2.7. In addition to destabilizing nascent TCR alpha proteins we found that persistence of Glc residues on core oligosaccharides markedly interfered with association of both TCR alpha and TCR beta glycoproteins with the molecular chaperone calnexin. Finally, using 2B4 T hybridoma cells in which TCR complexes are efficiently assembled, we found that rapid degradation of nascent TCR alpha proteins induced by impaired Glc trimming severely limits assembly of TCR alpha proteins with TCR beta proteins. These results demonstrate that the persistence of Glc residues on asparagine-linked (N-linked) oligosaccharide side chains (i) disrupts associations of calnexin with both TCR alpha and TCR beta proteins, (ii) results in destabilization of nascent TCR alpha proteins, and (iii) restricts the ability of TCR alpha and TCR beta proteins to assemble together. Thus, association with calnexin is uniquely important for the stabilization of nascent TCR alpha proteins within the ER. C1 UNIV TORONTO,DEPT BIOCHEM,TORONTO M5S 1A8,ON,CANADA. RP KEARSE, KP (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 40 TC 112 Z9 112 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1994 VL 13 IS 16 BP 3678 EP 3686 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PD661 UT WOS:A1994PD66100003 PM 7915231 ER PT J AU RASMUSSEN, C GAREN, C BRINING, S KINCAID, RL MEANS, RL MEANS, AR AF RASMUSSEN, C GAREN, C BRINING, S KINCAID, RL MEANS, RL MEANS, AR TI THE CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE CATALYTIC SUBUNIT (CALCINEURIN-A) IS AN ESSENTIAL GENE IN ASPERGILLUS-NIDULANS SO EMBO JOURNAL LA English DT Article DE ASPERGILLUS NIDULANS; CALCINEURIN A; CALMODULIN; CELL CYCLE PROGRESSION; CNAA(+) GENE ID CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; KINASE; EXPRESSION; CLONING; CALCIUM; YEAST; ACTIVATION; MITOSIS; NIMA AB The gene encoding the homologue of the catalytic subunit of the Ca2+/calmodulin-regulated protein phosphatase 2B (calcineurin A) has been isolated from Aspergillus nidulans. This gene, cna(A+), is essential in this fungal system. Analysis of growth-arrested cells following gene disruption by homologous recombination reveals that they are blocked early in the cell cycle. The cna(A+) gene encodes a 2.5 kb mRNA and the deduced protein sequence is highly homologous to the calcineurin A subunit of other species. The mNRA varies in a cell cycle-dependent manner with maximal levels found early in G(1) and considerably before the G(1)/S boundary. As calmodulin is also essential for A.nidulans cell cycle progression and levels rise before the G(1)/S boundary, our data suggest that calcineurin may represent a primary target for calmodulin at this cell cycle transition point. C1 DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. UNIV ALBERTA,DEPT ANAT & CELL BIOL,EDMONTON,AB,CANADA. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON,AB,CANADA. UNIV ALBERTA,DEPT ONCOL,EDMONTON,AB,CANADA. UNIV ALBERTA,NCI,MOLEC MECHANISMS GROWTH CONTROL GRP,EDMONTON,AB,CANADA. NIAAA,IMMUNOL SECT,ROCKVILLE,MD. NR 37 TC 40 Z9 41 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1994 VL 13 IS 16 BP 3917 EP 3924 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PD661 UT WOS:A1994PD66100028 PM 8070419 ER PT J AU PRASAD, GL FULDNER, RA BRAVERMAN, R MCDUFFIE, E COOPER, HL AF PRASAD, GL FULDNER, RA BRAVERMAN, R MCDUFFIE, E COOPER, HL TI EXPRESSION, CYTOSKELETAL UTILIZATION AND DIMER FORMATION OF TROPOMYOSIN DERIVED FROM RETROVIRAL-MEDIATED CDNA TRANSFER - METABOLISM OF TROPOMYOSIN FROM TRANSDUCED CDNA SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID CHICKEN-EMBRYO FIBROBLASTS; SMOOTH-MUSCLE TROPOMYOSIN; VIRUS-TRANSFORMED CELLS; RAT CULTURED-CELLS; NATIVE HETERODIMER; EPITHELIAL-CELLS; CHAIN EXCHANGE; SUPPRESSION; PROTEINS; ISOFORMS AB Expression of the tropomyosin-1 isoform was enhanced by cDNA transfer in non-transformed murine 3T3 fibroblasts and also in v-Ki-ras transformed fibroblasts in which native tropomyosin-1 expression had been reduced and tropomyosin-2 synthesis virtually eliminated by action of the oncogene. The level of synthesis of insert-derived tropomyosin-1 was similar in normal and transformed transductants (3-5 times normal levels). The high level of insert-derived tropomyosin-1 expression resulted in a considerable increase in tropomyosin-1 utilization in the cytoskeleton of transformed cells, but this expression still did not reach normal levels, suggesting an oncogene related inhibition of tropomyosin utilization. A large proportion of newly synthesized native tropomyosin-1 in normal, unmodified fibroblasts appeared in homodimers which, upon prolonged incubation, were largely converted to the heterodimers. Excess tropomyosin-1 derived from the inserted cDNA also appeared largely as the homodimer in both normal and transformed cells. This homodimer was utilized effectively in the formation of cytoskeletal structures but was partially converted to heterodimer by chain exchange. Under steady-state conditions, approximately 33% of the cytoskeletal tropomyosin-1-containing dimers were homodimers, compared to approximately 10% in normal fibroblasts. The results show that the increased amount of tropomyosin-1 homodimer entering the cytoskeleton under conditions of tropomyosin-1 excess, results in an atypical microfilament composition. The effect of this excess of tropomyosin-1 homodimers on stability or function of microfilament fibers remains to be determined. The results also confirm that the mechanisms of rapid homodimer formation with conversion to heterodimers by chain exchange, known from in vitro studies, also occur in vivo. C1 NCI,CELL MOLEC PHYSIOL SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD. NR 43 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 15 PY 1994 VL 224 IS 1 BP 1 EP 10 DI 10.1111/j.1432-1033.1994.tb19988.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC432 UT WOS:A1994PC43200001 PM 8076628 ER PT J AU TANCREDI, T SALVADORI, S AMODEO, P PICONE, D LAZARUS, LH BRYANT, SD GUERRINI, R MARZOLA, G TEMUSSI, PA AF TANCREDI, T SALVADORI, S AMODEO, P PICONE, D LAZARUS, LH BRYANT, SD GUERRINI, R MARZOLA, G TEMUSSI, PA TI CONVERSION OF ENKEPHALIN AND DERMORPHIN INTO DELTA-SELECTIVE OPIOID ANTAGONISTS BY SINGLE-RESIDUE SUBSTITUTION SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID CONFORMATIONAL PROPERTIES; RECEPTOR ANTAGONIST; LINEAR PEPTIDES; AMPHIBIAN SKIN; NUCLEIC-ACIDS; HIGH-AFFINITY; FORCE-FIELD; DELTORPHIN; PROTEINS; SPECTROSCOPY AB The properties of di- and tri-peptides containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in second position suggest that the message domain of opioid peptides can be composed of only two residues [Temussi, P. A., Salvadori, S., Amodeo, P., Guerrini, R., Tomatis, R., Lazarus, L. H., Picone, D. gr Tancredi, T. (1994) Biochem. Biophys. Res. Commun. 198, 933-939]. As a crucial test of the possibility that the Sr-Tic segment be a message domain in longer peptide sequences, we have inserted it in the sequences of two typical opioid peptides: [Leu]enkephalin, a non-selective agonist, and dermorphin, a selective mu agonist. Here we report the synthesis and biological activity of [L-Tic(2)]enkephalin, [L-Tic(2)]dermorphin, [L-Tic(2)]dermorphin carboxylic acid and [D-Tic(2)]dermorphin: all [L-Tic(2)]peptides were converted from agonists to delta-selective antagonists. The NMR conformational study in a dimethylsulfoxide/water cryoprotective mixture at low temperature shows diagnostic side-chain - side-chain NOEs in the spectra of all [L-Tic(2)]peptides and hints that the 90 degrees arrangement of the the two aromatic rings found in the cis-Tyr-L-Tic moiety, typical of N-methyl naltrindole and other delta-selective opiate antagonists, is responsible for the antagonist activity of all these peptides. C1 UNIV NAPLES,DIPARTIMENTO CHIM,I-80134 NAPLES,ITALY. CNR,IST CHIM MOLEC INTERESSE BIOL,NAPLES,ITALY. NIEHS,LMNI,RES TRIANGLE PK,NC. UNIV FERRARA,IST FARMACOL,I-44100 FERRARA,ITALY. RI Picone, Delia/I-5605-2012; Amodeo, Pietro/P-1800-2015; OI Picone, Delia/0000-0002-7582-2581; Amodeo, Pietro/0000-0002-6439-7575; Guerrini, Remo/0000-0002-7619-0918 NR 39 TC 39 Z9 39 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 15 PY 1994 VL 224 IS 1 BP 241 EP 247 DI 10.1111/j.1432-1033.1994.tb20017.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PC432 UT WOS:A1994PC43200030 PM 8076645 ER PT J AU PURI, RK LELAND, P KREITMAN, RJ PASTAN, I AF PURI, RK LELAND, P KREITMAN, RJ PASTAN, I TI HUMAN NEUROLOGICAL CANCER-CELLS EXPRESS INTERLEUKIN-4 (IL-4) RECEPTORS WHICH ARE TARGETS FOR THE TOXIC EFFECTS OF IL4-PSEUDOMONAS EXOTOXIN CHIMERIC PROTEIN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PSEUDOMONAS EXOTOXIN; HIGH-AFFINITY; CARCINOMA-CELLS; TUMOR-CELLS; GAMMA-CHAIN; GROWTH; INHIBITION; IDENTIFICATION; THERAPY; INVIVO AB Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL-4 receptors (IL-4R) by now cytometric analysis and I-125-IL-4 binding. These cancer cell lines expressed IL-4R which were of high affinity (K-D = 700 x 10(-12) M) on glioblastoma cells. To investigate the function of these receptors and to target potent cytotoxic antitumor agents to human neurological cancers, we utilized IL4-PE4E, which is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). This chimeric molecule was cytotoxic toward human glioblastoma, neuroblastoma and glioma tumor cells in a dose-dependent manner. The cytotoxicity of IL4-PE4E was specific, since it was neutralized by excess IL-4, and by an anti-IL-4 monoclonal antibody in all types of brain tumor tested. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mutant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediated cytotoxicity of the brain tumor cells required both IL-4R binding and enzymatic toxin activity. These data indicate that human neurological cancer cells express IL-4R which are targets for the cytotoxic effects of IL4-toxin. In addition, our data also suggest that IL4-PE4E should be studied further as a potential treatment for human neurological cancers. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RP PURI, RK (reprint author), NIH,US FDA,CBER,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LA,BLDG 29A,ROOM 2B23,BETHESDA,MD 20892, USA. NR 29 TC 94 Z9 98 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 15 PY 1994 VL 58 IS 4 BP 574 EP 581 DI 10.1002/ijc.2910580421 PG 8 WC Oncology SC Oncology GA PB589 UT WOS:A1994PB58900020 PM 8056454 ER PT J AU NAKANISHI, H TAYLOR, RM HAWKINS, AL GRIFFIN, CA MARTIN, GR PASSANITI, A AF NAKANISHI, H TAYLOR, RM HAWKINS, AL GRIFFIN, CA MARTIN, GR PASSANITI, A TI ESTABLISHMENT OF HORMONE-DEPENDENT AND HORMONE-INDEPENDENT CARCINOMA CELL-LINES WITH DIFFERENT METASTATIC POTENTIALS FROM SPONTANEOUS MAMMARY-TUMORS IN AGED WISTAR RATS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NEGATIVE BREAST-CANCER; PROGESTERONE RECEPTORS; ESTROGEN; MUTATIONS; P53; ABNORMALITIES; TUMORIGENESIS; EXPRESSION; VIMENTIN AB Three stable carcinoma cell lines, designated RM22-F5, RM17-5R, and RM1-4, were established from spontaneously occurring mammary carcinomas in old, outbred, female Wistar rats. The RM22-F5 and RM17-5R cells were keratin-positive and formed epithelial monolayers, whereas RM1-4 cells exhibited a spindlelike morphology and intense vimentin staining. When injected into nude mice, RM22-F5, RM17-5R and RM1-4 cells formed well differentiated, poorly differentiated and undifferentiated carcinomas, respectively. The relative growth rates of the tumor cells in vitro were RM1-4 > RM22-F5 > RM17-5R. The growth of RM22-F5, but not of RM17-5R and RM1-4 cells, was significantly stimulated by insulin, epidermal growth factor, dexamethasone, 17 beta-estradiol and progesterone in vitro. Ovariectomy reduced the growth of RM22-F5 cells in vivo and these cells (but not RM1-4 or RM17-5R) were estrogen-receptor (ER)-positive. None of the lines were positive for the progesterone receptor (PR), Spontaneous lung and lymph-node metastases were observed in nude mice injected with RM22-F5 or RM17-5R cells, respectively. In contrast, RM1-4 cells were non-metastatic but invasive. Karyotype analysis revealed that RM22-F5 cells were hyperdiploid, RM17-5R were hypotetraploid, and RM1-4 were diploid with a sizeable insertion in chromosome I.A point mutation in codon 12 (G to A transition) and loss of the normal allele of the H-ras-1 gene was detected in the DNA from RM22-F5 cells. No p53 mutations were apparent in any of the cell lines. The results indicate that RM22-F5 cells are hormone-dependent with an ER(+)/PR(-) phenotype, while the RM17-5R and RM1-4 lines are hormone-independent and ER(-)/PR(-). These cell lines exhibit the spectrum of biological properties and genetic alterations observed in human breast cancers and may, therefore, be novel and useful models for understanding sporadic breast cancer in post-menopausal women. (C) 1994 Wiley-Liss, Inc. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT PATHOL & DERMATOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,CTR ONCOL,CYTOGENET LAB,BALTIMORE,MD 21205. NR 31 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 15 PY 1994 VL 58 IS 4 BP 592 EP 601 DI 10.1002/ijc.2910580424 PG 10 WC Oncology SC Oncology GA PB589 UT WOS:A1994PB58900023 PM 8056457 ER PT J AU KITANI, A STROBER, W AF KITANI, A STROBER, W TI DIFFERENTIAL REGULATION OF C-ALPHA-1 AND C-ALPHA-2 GERM-LINE AND MATURE MESSENGER-RNA TRANSCRIPTS IN HUMAN PERIPHERAL-BLOOD B-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN TRANSCRIPTS; CONSTANT-REGION GENES; C-EPSILON TRANSCRIPTS; IMMUNOGLOBULIN-A; CD40 LIGAND; LYMPHOCYTES-B; TYROSINE PHOSPHORYLATION; SWITCH RECOMBINATION; MONOCLONAL-ANTIBODY; IGA SUBCLASSES AB In this study, we investigated the regulation of germ-line and mature C alpha mRNA transcript expression in human peripheral blood B cells. In initial studies, we found that C alpha germ-line and mature transcripts were constitutively expressed in total peripheral blood B cells but not in high density surface IgM(+) (surface IgA(-)) B cells; the latter cells were therefore used in subsequent studies. Focusing first on regulation of germ-line (I alpha-C alpha) transcripts, we showed that C alpha 1 germ-line transcripts are induced by TGF-beta 1 alone but such induction is enhanced by Staphylococcus aureus, Cowan I (SAC). In contrast, C alpha 2 germ-line transcripts are optimally induced by TGF-beta 1 in the absence of a B cell stimulus. In addition, although SAC alone induced both C alpha 1 and C alpha 2 germ-line transcripts, such induction is dependent on endogenous (B cell-derived) TCF-beta 1 production, because no induction is detected in cells cultured in the presence of neutralizing anti-TGF-beta 1. Turning next to mature (VDJ-C alpha) transcripts we showed that SAC plus TGF-beta 1 induces mature C alpha 1 transcripts, and such induction is IL-10 dependent because it is enhanced by exogenous IL-10 and abrogated by the presence of anti-IL-10. In contrast, SAC plus TGF-beta 1 does not induce C alpha 2 mature transcripts, even in the presence of exogenous IL-10; such transcripts are induced, however, by T cell stimuli such as anti-CD40 (presented by CDw32-transfected L cells) in the presence of TGF-beta 1/IL-10 or by PWM-activated T cells. In summary, these studies show that C alpha 1 and C alpha 2 germ-line transcript induction is differentially regulated, in keeping with previous studies of differences in germ-line CH transcript induction in the first and second IgH duplication units. Furthermore, C alpha 1 and C alpha 2 mature transcript induction is also differentially regulated, with C alpha 2 requiring a T cell signal such as that delivered by the CD40 ligand. Finally, IL-10 appears to be uniquely supportive of the induction of both C alpha 1 and C alpha 2 mature transcripts. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 55 TC 33 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1466 EP 1477 PG 12 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600007 PM 8046226 ER PT J AU LONG, EO LAVAUTE, T PINET, V JARAQUEMADA, D AF LONG, EO LAVAUTE, T PINET, V JARAQUEMADA, D TI INVARIANT CHAIN PREVENTS THE HLA-DR-RESTRICTED PRESENTATION OF A CYTOSOLIC PEPTIDE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ROUGH ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; HISTOCOMPATIBILITY ANTIGENS; MICE LACKING; BETA-DIMERS; T-CELLS; COMPLEX; GENE; EXPRESSION; MOLECULES AB Three properties of the HLA-DR-associated invariant chain (li) may contribute to the distinction between the class I and class II Ag presentation pathways. First, li prevents peptide binding to alpha beta li complexes. Second, li promotes assembly of class II alpha beta heterodimers and their transport out of the endoplasmic reticulum. Third, li provides a targeting signal for the transport of class II molecules to endocytic compartments. However, it is not known whether li can prevent class li-restricted T cell recognition of endogenous peptides transported into the endoplasmic reticulum. In addition, recent evidence has indicated that, in the absence of li, newly synthesized class II molecules cannot form stable complexes with peptides. In this study, transfected human fibroblast cells expressing HLA-DR1 alone or with an excess of li were tested for their ability to present a DR1-restricted epitope of the influenza virus matrix protein produced as a short cytosolic peptide by use of an episomal expression vector. Presentation to a DR1-restricted T cell clone was very efficient in cells expressing class II molecules without li, but not in cells expressing class II with li. The inhibition by li was specific for the endogenous cytosolic peptide, because the same epitope processed from exogenous influenza virus particles was presented only by cells expressing class II with li. li did not inhibit the HLA-A2-restricted presentation of another cytosolic peptide. Thus, T cells can detect a cytosolic peptide loaded onto class II alpha beta heterodimers, and li prevents such endogenous peptide presentation. RP LONG, EO (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011; PINET, Valerie/G-6085-2012 OI Long, Eric/0000-0002-7793-3728; NR 42 TC 46 Z9 46 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1487 EP 1494 PG 8 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600009 PM 8046228 ER PT J AU NETA, R OPPENHEIM, JJ WANG, JM SNAPPER, CM MOORMAN, MA DUBOIS, CM AF NETA, R OPPENHEIM, JJ WANG, JM SNAPPER, CM MOORMAN, MA DUBOIS, CM TI SYNERGY OF IL-1 AND STEM-CELL FACTOR IN RADIOPROTECTION OF MICE IS ASSOCIATED WITH IL-1 UP-REGULATION OF MESSENGER-RNA AND PROTEIN EXPRESSION FOR C-KIT ON BONE-MARROW CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; RECOMBINANT INTERLEUKIN 1-ALPHA; IRRADIATED MICE; GROWTH-FACTOR; FACTOR-ALPHA; INVIVO; MODULATION; LIGAND; IDENTIFICATION AB Administration of IL-1 and stem cell factor (SCF) to mice 18 h before lethal Co-60 whole-body irradiation resulted in synergistic radioprotection, as evidenced by increased numbers of mice surviving 1,200 to 1,300 cGy doses of radiation and the recovery of increased numbers of c-kit(+) bone marrow cells at 1 and 4 days after the lethal dose of 950 cGy. Anti-SCF Ab inhibited IL-1-induced radioprotection, indicating that endogenous production of SCF is necessary for radioprotection by IL-1. Conversely, radioprotection induced by SCF was reduced by anti-IL-1R Ab, indicating that endogenous IL-1 contributes to SCF radioprotection. SCF, unlike IL-1, does not induce hemopoietic CSFs and IL-6 or gene expression of a scavenging mitochondrial enzyme manganese superoxide dismutase in the bone marrow, suggesting that SCF and IL-1 radioprotect by distinct pathways. The mRNA expression for c-kit (by Northern blot analysis) and I-125-SCF binding on bone marrow cells was elevated within 2 and 4 h of IL-1 administration respectively. Four days after LD 100/30 radiation the recovery of c-kit(+) bone marrow cells was increased sixfold in IL-1-treated mice, almost 20-fold in SCF-treated mice, and 40-fold in mice treated with the combination of the two cytokines. Thus, endogenous production of both IL-1 and SCF is required for resistance to lethal irradiation and the synergistic radioprotective effect of the two cytokines may, in part, depend on IL-1 and SCF-induced increases in numbers of c-kit(+) hemopoietic stem and progenitors cells that survive lethal irradiation. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20889. UNIV SHERBROOKE,SHERBROOKE J1K 2R1,PQ,CANADA. RP NETA, R (reprint author), ARMED FORCES RADIOBIOL RES INST,DEPT EXPTL HEMATOL,BETHESDA,MD 20889, USA. NR 37 TC 51 Z9 56 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1536 EP 1543 PG 8 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600014 PM 7519205 ER PT J AU VOGT, AB KROPSHOFER, H KALBACHER, H KALBUS, M RAMMENSEE, HG COLIGAN, JE MARTIN, R AF VOGT, AB KROPSHOFER, H KALBACHER, H KALBUS, M RAMMENSEE, HG COLIGAN, JE MARTIN, R TI LIGAND MOTIFS OF HLA-DRB5-ASTERISK-0101 AND DRB1-ASTERISK-1501 MOLECULES DELINEATED FROM SELF-PEPTIDES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS PATIENTS; T-CELL RESPONSE; HLA-DR ALLELES; FINE SPECIFICITY; BINDING; RECOGNITION; HLA-DR1; IDENTIFICATION; RESTRICTION AB Antigenic peptides are presented to CD4(+) T cells by MHC class II molecules via a highly polymorphic peptide-binding groove. The two HLA-DR alleles isotypically expressed on HLA-DR15Dw2-positive cells, DRB1*1501 (DR2b) and DRB5*0101 (DR2a) molecules, show a number of differences in polymorphic residues of the beta-chain, including the Gly-Val-dimorphism at position beta 86. Therefore, different requirements for interaction of peptides with these alleles must be expected. In this study, naturally processed self-peptides were eluted from purified HLA-DR15Dw2 molecules and related to DRB1*1501 or DRB5*0101 molecules by binding assays. An alignment of self-peptides and foreign peptides allowed the delineation of putative anchor motifs. N- and C-terminally truncated and alanine-substituted derivatives of the DR15Dw2 restricted myelin basic protein epitope MBP(85-105) confirmed their validity. Thus, DRB5*0101 requires a bulky hydrophobic residue (F or Y) at position i as a primary anchor, and Q or an aliphatic residue, such as V, I, or M, at position 1 + 3; positively charged residues at positions 1 + 7 and 1 + 8 are secondary anchors. For DRB1*1501, a nonaromatic, hydrophobic anchor (L, V, or I) at position i is supplemented by a bulky hydrophobic residue (F or Y) at position i + 3 as primary anchor; an additional hydrophobic side chain respresented by M, I, V, or F occurs at position i + 6. Therefore, MBP(85-105) seems to contain two MHC interaction sites for DRB1*1501 and DRB5*0101, respectively, that may contribute to its immunodominance. Because HLA-DR15 Dw2 is associated with susceptibility to develop multiple sclerosis, the delineation of ligand motifs of the two DR2 alleles may help to study the interaction between potential autoantigenic peptides and these molecules in the future. C1 UNIV TUBINGEN,SCH MED,DEPT NEUROL,D-72076 TUBINGEN,GERMANY. UNIV TUBINGEN,CTR MED & NAT SCI,TUBINGEN,GERMANY. GERMAN CANC RES CTR,TUMOR IMMUNOL PROGRAM,W-6900 HEIDELBERG,GERMANY. GERMAN CANC RES CTR,DEPT TUMORVIRUS IMMUNOL,W-6900 HEIDELBERG,GERMANY. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. NR 33 TC 147 Z9 148 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1665 EP 1673 PG 9 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600026 PM 7519208 ER PT J AU OSWALD, IP CASPAR, P JANKOVIC, D WYNN, TA PEARCE, EJ SHER, A AF OSWALD, IP CASPAR, P JANKOVIC, D WYNN, TA PEARCE, EJ SHER, A TI IL-12 INHIBITS TH2 CYTOKINE RESPONSES INDUCED BY EGGS OF SCHISTOSOMA-MANSONI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; CD4+ T-CELLS; NATURAL-KILLER-CELLS; GRANULOMA-FORMATION; STIMULATORY FACTOR; IFN-GAMMA; INTERLEUKIN-12; INDUCTION; MICE; MACROPHAGES AB In the mouse, infection with the helminth parasite Schistosoma mansoni results in the selective induction of CD4(+) T lymphocytes belonging to the Th2 subset. Schistosome ova are responsible for the development of Th2 responses seen in patently infected animals and the injection of eggs s.c. into the footpad leads to the development of elevated Th2 cytokine production by T cells in the draining popliteal lymph node. Using the egg injection model, we have shown that IL-12 suppresses schistosome egg-induced Th2 responses as evidenced by decreased IL-4, IL-5, and IL-10 secretion in vitro while increasing the production of the Th1 cytokine IFN-gamma. Similar responses were obtained using either total lymph node cells or purified CD4(+) T cells, indicating that IL-12 acts at the T cell level. When given as a single injection IL-12 was most effective at inhibiting Th2 responses when administered 2 days after egg inoculation, a time when T cells are still in a Th0 phase. The suppression of Th2 responses induced by IL-12 was blocked when the animals were simultaneously injected with neutralizing anti-IFN-gamma mAb, either systemically or systemically plus locally. Anti-IFN-gamma also inhibited the enhancement of IFN-gamma responses induced by IL-12 but only if the mAb was administered systemically plus locally. NK cells are likely to be a major source of the immunoregulatory IFN-gamma, because the effects of IL-12 on Th2 cytokine production were suppressed in mice treated with anti-asialo-GM1 Abs. Together these results suggest that IL-12 may have potential use in preventing or treating parasite-induced pathology resulting from Th2 cytokine production. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20814. CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT MICROBIOL IMMUNOL & PARASITOL,ITHACA,NY 14853. RI Wynn, Thomas/C-2797-2011; OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 28 TC 107 Z9 110 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1707 EP 1713 PG 7 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600030 PM 7913944 ER PT J AU JOHNSTON, JA TAUB, DD LLOYD, AR CONLON, K OPPENHEIM, JJ KEVLIN, DJ AF JOHNSTON, JA TAUB, DD LLOYD, AR CONLON, K OPPENHEIM, JJ KEVLIN, DJ TI HUMAN T-LYMPHOCYTE CHEMOTAXIS AND ADHESION INDUCED BY VASOACTIVE-INTESTINAL-PEPTIDE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; CELLS; BINDING; CLONING; NEUROENDOCRINE; MIP-1-BETA; GROWTH; LUNG AB Vasoactive intestinal peptide (VIP), a 28-amino acid peptide of the glucagon-secretin family, has been reported to have significant immunoregulatory properties. In the present study, we demonstrate that VIP has potent chemotactic effects on T lymphocytes. At concentrations of between 10(-8) and 10(-9) M, VIP stimulated significant in vitro chemotaxis of T lymphocytes from both CD4(+) and CD8(+) subsets. VIP produced more potent chemotactic effects on unstimulated T cells than on anti-CD3-activated cells. Following anti-CD3 activation, binding of I-125-labeled VIP to T cells was reduced and this correlated with a reduction in receptor number without any change in affinity. Preincubation of unstimulated T cells with VIP produced increases in adhesion to ICAM and VCAM integrins. In addition, VIP pretreatment significantly increased unstimulated T cell adhesion to the extracellular matrix protein fibronectin. However, VIP induced less binding of activated T cells to fibronectin. Taken together these results suggest that VIP is a potent chemoattractant and stimulant of adhesion for T lymphocytes. In contrast to chemokines that are more active on stimulated T cells, such as RANTES, this neuropeptide preferentially targets unactivated T cells, suggesting that it may play a greater role in homing and distribution of lymphocytes. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP JOHNSTON, JA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [1-CO-74102] NR 25 TC 85 Z9 86 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1762 EP 1768 PG 7 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600036 PM 7519212 ER PT J AU YAN, L VANDIVIER, RW SUFFREDINI, AF DANNER, RL AF YAN, L VANDIVIER, RW SUFFREDINI, AF DANNER, RL TI HUMAN POLYMORPHONUCLEAR LEUKOCYTES LACK DETECTABLE NITRIC-OXIDE SYNTHASE ACTIVITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; TUMOR-NECROSIS-FACTOR; MONOMETHYL-L-ARGININE; HUMAN-NEUTROPHILS; PLATELET-AGGREGATION; CYCLIC-GMP; MONONUCLEAR PHAGOCYTES; ENDOTHELIAL-CELLS; CATHEPSIN-G; TNF-ALPHA AB Nitric oxide regulates polymorphonuclear leukocyte (PMN) function, but whether or not human PMNs express nitric oxide synthase (NOS) activity is controversial. We studied NOS activity in human PMNs by using human aortic endothelial cells (HAECs) for comparison. The conversion of L-arginine to L-citrulline, a relatively specific measure of NOS activity, was easily measured and inducible in fractionated HAECs, and >90% of all L-arginine conversion was blocked by the NOS inhibitor, N-omega-amino-L-arginine (L-NAA). In fractionated PMNs, L-arginine conversion was low and was unaffected by L-NAA. In addition, NOS activity was not induced in PMNs by LPS, IL-1 beta, or IFN-gamma. In a whole-cell assay, total L-arginine conversion was much lower in human PMNs compared with HAECs (3.38 +/- 0.21 vs 157.5 +/- 10.28 pmol/h/10(6) cells, respectively; p < 0.01). This conversion in whole PMNs was not increased in vitro by LPS, IFN-gamma, IL-1 beta, or TNF-alpha nor decreased by W13, a calmodulin inhibitor. Furthermore, PMNs isolated from four volunteers before and after challenge with i.v. LPS (4 ng/kg) showed no increase in L-arginine to L-citrulline conversion. Nitrite and nitrate release from human PMNs was 35-fold lower than for HAECs and was not inhibited by L-NAA. These data suggest that human PMNs do not express NOS activity. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 70 TC 88 Z9 91 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1994 VL 153 IS 4 BP 1825 EP 1834 PG 10 WC Immunology SC Immunology GA PB406 UT WOS:A1994PB40600043 PM 7519215 ER PT J AU ELLENBERG, JH GAIL, MH SIMON, RH AF ELLENBERG, JH GAIL, MH SIMON, RH TI NATIONAL-INSTITUTES-OF-HEALTH CONFERENCE ON CURRENT TOPICS IN BIOSTATISTICS (VOL 13, PG 1600, 1994) SO STATISTICS IN MEDICINE LA English DT Correction, Addition C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP ELLENBERG, JH (reprint author), US FDA,CBER,OELPS,DIV BIOSTAT & EPIDEMIOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 15 PY 1994 VL 13 IS 15 BP 1600 EP 1600 PG 1 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PF482 UT WOS:A1994PF48200009 ER PT J AU AGBANDJE, M KAJIGAYA, S MCKENNA, R YOUNG, NS ROSSMANN, MG AF AGBANDJE, M KAJIGAYA, S MCKENNA, R YOUNG, NS ROSSMANN, MG TI THE STRUCTURE OF HUMAN PARVOVIRUS-B19 AT 8-ANGSTROM RESOLUTION SO VIROLOGY LA English DT Article ID FUNCTIONAL IMPLICATIONS; BACULOVIRUS SYSTEM; APLASTIC CRISIS; EMPTY CAPSIDS; VIRUS; INFECTION; PROTEINS; ANEMIA; PARTICLES; SEQUENCE AB Empty capsids of the human parvovirus B19, self-assembled in a baculovirus expression system, have been crystallized in a cubic space group P2,3 with a = 362 Angstrom. In spite of extensive purifications, the crystals diffract X-rays to only 8.0 Angstrom A resolution. Diffraction data were collected using oscillation photography with synchrotron radiation. The orientations of the particles in the unit cell were determined with a self-rotation function and their positions were obtained with an R-factor search using the known homologous canine parvovirus (CPV) structure. The resultant phases were improved by electron density averaging and solvent flattening to include all the terms between 23.0 and 8.0 Angstrom resolution. The central eight-stranded antiparallel beta-barrel, common to many viruses, is situated similarly in B19 with respect to the icosaheral symmetry axes to that observed for feline panleukopenia virus (FPV) and CPV. However, the surface structure of B19 is significantly different from the other known parvoviruses. The most striking difference is that B19 lacks the prominent spikes on the threefold icosahedral axes observed in FPV and CPV. This spike region contains residues involved in host recognition and antigenicity for the latter viruses, showing that there are major differences between subgroups of autonomous parvoviruses. (C) 1994 Academic Press, Inc, C1 PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 43 TC 82 Z9 85 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 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 1994 VL 203 IS 1 BP 106 EP 115 DI 10.1006/viro.1994.1460 PG 10 WC Virology SC Virology GA NZ236 UT WOS:A1994NZ23600013 PM 8030266 ER PT J AU BRAUN, MM CAPORASO, NE PAGE, WF HOOVER, RN AF BRAUN, MM CAPORASO, NE PAGE, WF HOOVER, RN TI GENETIC COMPONENT OF LUNG-CANCER - COHORT STUDY OF TWINS SO LANCET LA English DT Article ID RISK; SUSCEPTIBILITY; ASSOCIATION; STATISTICS; MUTATIONS; MORTALITY; REGISTRY; SMOKING; LOCUS AB Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15 924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0.75 [95% CI 0.35-1.6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4.09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur. C1 NATL ACAD SCI,INST MED,MED FOLLOW UP AGCY,WASHINGTON,DC 20418. RP BRAUN, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 443,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 30 TC 50 Z9 50 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 13 PY 1994 VL 344 IS 8920 BP 440 EP 443 DI 10.1016/S0140-6736(94)91770-1 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PB761 UT WOS:A1994PB76100010 PM 7914565 ER PT J AU CHU, E VOELLER, DM MORRISON, PF JONES, KL TAKECHI, T MALEY, GF MALEY, F ALLEGRA, CJ AF CHU, E VOELLER, DM MORRISON, PF JONES, KL TAKECHI, T MALEY, GF MALEY, F ALLEGRA, CJ TI THE EFFECT OF REDUCING REAGENTS ON BINDING OF THYMIDYLATE SYNTHASE PROTEIN TO THYMIDYLATE SYNTHASE MESSENGER-RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATION-REDUCTION; REDOX REGULATION; COAT PROTEIN; SYNTHETASE; SEQUENCE; SITE; DNA; INVITRO; BACTERIOPHAGE-T4; TRANSLATION AB Human thymidylate synthase (TS) protein specifically binds to its own TS mRNA and functions as a translational repressor. In the presence of reducing agents, the RNA binding activity of TS protein is significantly enhanced. In contrast, treatment of TS protein with the oxidizing agent diamide inhibits RNA binding. Scatchard analysis reveals that in the presence of the reducing agent 2-mercaptoethanol, the TS protein/TS mRNA interaction changes from low (K-d = 66 nM) to high (K-d = 2.6 nM) apparent affinity. The catalytic activity of TS is increased by up to 6.5-fold in the presence of 2-mercaptoethanol. These studies demonstrate that the interaction between TS protein and its target TS mRNA is sensitive to the presence of reducing reagents and is dependent upon a reversible sulfhydryl switch mechanism. C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. RP CHU, E (reprint author), USN HOSP,NCI,NAVY MED ONCOL BRANCH,BLDG 8,RM 5101,8901 WISCONSIN AVE,BETHESDA,MD 20889, USA. NR 38 TC 34 Z9 35 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 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 12 PY 1994 VL 269 IS 32 BP 20289 EP 20293 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700015 PM 8051122 ER PT J AU LAZAR, J DESVERGNE, B ZIMMERMAN, EC ZIMMER, DB MAGNUSON, MA NIKODEM, VM AF LAZAR, J DESVERGNE, B ZIMMERMAN, EC ZIMMER, DB MAGNUSON, MA NIKODEM, VM TI A ROLE FOR INTRONIC SEQUENCES ON EXPRESSION OF THYROID-HORMONE RECEPTOR-ALPHA GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAVY-CHAIN PROMOTER; DOMAIN TRANSCRIPTION FACTORS; RESPONSE ELEMENT; REGULATORY ELEMENTS; MEDIATES INDUCTION; C-ERBA-1 GENE; OCTAMER MOTIF; DNA-BINDING; 1ST INTRON; PROTEIN AB We have cloned and characterized the organization of the rat thyroid hormone receptor alpha (THR) gene. Multiple transcription start sites were mapped by RNA primer extension analyses. The promoter of the rat THR alpha gene does not contain a TATA or CAAT box. Deletion analyses of the 5' region of THR alpha gene and transfection assays, using NIH3T3 and NG108-15 cells, revealed that the sequences from -137 to +205 (+205 resides in the first intron) are necessary for efficient expression of this gene. This region contains two positively acting elements, the sequence -137 to -60 upstream from the major start of transcription and three copies of an AGG sequence located in the first intron. In contrast, two octamer-binding motifs in the first intron function as the negative regulatory elements. Gel mobility shift assays showed that the purine-rich sequence and the octamer-binding motifs bind to a protein(s) present in NIH3T3 and NG108-15 cells, the recipients in transient transfection assays. Genomic sequence comparison of THR alpha and beta revealed the presence of the purine-rich track in both genes, while the octamer-binding motifs were found only in the alpha gene. These results might explain the differential regulation of THR alpha and beta gene expression previously noted. C1 NIDDKD,GENET & BIOCHEM BRANCH,MECHANISMS GENE REGULAT SECT,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT MOLEC PHYSIOL & BIOPHYS,NASHVILLE,TN 37232. RI Magnuson, Mark/B-1335-2009; Desvergne, Beatrice/C-8892-2016 OI Magnuson, Mark/0000-0002-8824-6499; Desvergne, Beatrice/0000-0001-5483-288X NR 44 TC 16 Z9 16 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 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 12 PY 1994 VL 269 IS 32 BP 20352 EP 20359 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700025 PM 8051130 ER PT J AU KOHNO, K TANIMURA, H SATO, S NAKAYAMA, Y MAKINO, Y WADA, M FOJO, AT KUWANO, M AF KOHNO, K TANIMURA, H SATO, S NAKAYAMA, Y MAKINO, Y WADA, M FOJO, AT KUWANO, M TI CELLULAR CONTROL OF HUMAN MULTIDRUG-RESISTANCE-1 (MDR-1) GENE-EXPRESSION IN ABSENCE AND PRESENCE OF GENE AMPLIFICATION IN HUMAN CANCER-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DRUG-RESISTANCE; CARCINOMA-CELLS; HEAT-SHOCK; DNA; PROMOTER; LINES; ACTIVATION; MODULATION; SEQUENCE; AGENTS AB The Kst-6 cell line is a human KB carcinoma cell line that has a stably integrated chloramphenicol acetyltransferase (CAT) reporter gene under the control of the human mdr-1 promoter. Using Kst-6 cells as the parental cell line, five vincristine resistant sublines, designated Kst-V5, -V25, V50, -V75, and -V100, were isolated by exposure to increasing concentrations of drug. These sublines showed increased resistance to vincristine when compared with parental Kst-6 cells. Two sublines, V25-1 and V25-2, were further isolated from Kst-V25 after culture in the presence of vincristine, and V100-1 and V100-2 were also isolated from Kst-V100. Southern analysis demonstrated mdr-1 gene amplification in Kst-V50, Kst-V75, Kst-V100, V100-1, and V100-2 cells, respectively, but not in Kst-V5, Kst-V25, V25-1, and V25-2 cells. In contrast, increased mdr-1 expression was documented by Northern analysis in Kst-V25, V25-1, and V25-2 cells and five cell lines with mdr-1 amplification. Southern blot analysis utilizing a CAT probe demonstrated a stable copy number in all vincristine-resistant sublines. However, Northern analysis documented increased CAT expression in Kst-V5, Kst-V25, V25-1, and V25-2 cells but reduced mRNA levels in the cell line with amplification of the endogenous mdr-1 gene. Expression of the CAT gene was increased along with the endogenous mdr-1 gene in the early steps of the selection but decreased with the onset of gene amplification. There appeared almost similar mRNA levels of two trans-acting factor genes, SP-1 and MDR-NF1/YB-1, which are supposed to be involved in mdr-1 gene promoter activation, among all cell lines used in this study. These findings suggest that transcription of both the CAT gene fused to the mdr-1 promoter and the endogenous mdr-1 gene is enhanced through activation by trans-acting factors in the early steps of drug selection. However, the quantity of trans-activating factor is limiting, and with the onset of gene amplification, less is available for activation of the CAT gene, resulting in decreased expression. C1 NCI, MED BRANCH, BETHESDA, MD 20892 USA. RP KOHNO, K (reprint author), KYUSHU UNIV, SCH MED, DEPT BIOCHEM, FUKUOKA 812, JAPAN. NR 37 TC 45 Z9 45 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 AUG 12 PY 1994 VL 269 IS 32 BP 20503 EP 20508 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700047 PM 7914196 ER PT J AU SURRATT, CK JOHNSON, PS MORIWAKI, A SEIDLECK, BK BLASCHAK, CJ WANG, JB UHL, GR AF SURRATT, CK JOHNSON, PS MORIWAKI, A SEIDLECK, BK BLASCHAK, CJ WANG, JB UHL, GR TI -MU OPIATE RECEPTOR - CHARGED TRANSMEMBRANE DOMAIN AMINO-ACIDS ARE CRITICAL FOR AGONIST RECOGNITION AND INTRINSIC ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; DELTA-OPIOID RECEPTOR; HUMAN BETA-2-ADRENERGIC RECEPTOR; SCHIFF-BASE COUNTERION; LIGAND-BINDING; RAT-BRAIN; FUNCTIONAL EXPRESSION; BOVINE RHODOPSIN; ASPARTIC-ACID AB The mu opiate receptor is a principal brain site for activities of morphine, other opiate drugs, and opioid peptides in modulating pain and altering mood. Recent cloning of cDNAs encoding rat and human mu receptors reveals charged amino acid residues within putative transmembrane domains (TMs) II, III, and VI, a substantial N-terminal extracellular domain, and a C-terminal intracellular domain. Deletion of 64 N-terminal amino acids produced little effect on receptor function (Wang, J. B., Imai, Y., Eppler, C. M., Gregor, P., Spivak, C. E., and Uhl, G. R. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 10230-10234). Further deletion of 33 C-terminal amino acids yielded a receptor at which morphine, but not the substituted enkephalin DAMGO ([D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin), inhibited adenylate cyclase. Alanine substitution for each charged TM residue in the N-terminally deleted receptor reduced affinities for morphine, DAMGO, and the opiate antagonist naloxone. Replacement of TM II Asp(114) with asparagine or glutamic acid increased p receptor affinity for naloxone. TM II and TM III glutamic acid substitutions for Asp(114) and Asp(147) reduced agonist binding affinities but allowed full inhibition of adenylate cyclase at high agonist concentrations. TM VI histidine substitution with alanine yielded a receptor that produced almost twice the cyclase inhibition displayed by the wild type receptor in parallel transient expression assays. These findings underscore the importance of charged residues in TM II, III, and VI for different receptor functions and the modest involvement of extensive portions of N and C-terminaI receptor domains in these processes. C1 NIDA,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,INTRAMURAL RES PROGRAM,OFF DIRECTOR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 53 TC 223 Z9 227 U1 2 U2 5 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 AUG 12 PY 1994 VL 269 IS 32 BP 20548 EP 20553 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700054 PM 8051154 ER PT J AU SCHNIERLE, BS GERSHON, PD MOSS, B AF SCHNIERLE, BS GERSHON, PD MOSS, B TI MUTATIONAL ANALYSIS OF A MULTIFUNCTIONAL PROTEIN, WITH MESSENGER-RNA 5' CAP-SPECIFIC (NUCLEOSIDE-2'-O-)-METHYLTRANSFERASE AND 3'-ADENYLYLTRANSFERASE STIMULATORY ACTIVITIES, ENCODED BY VACCINIA VIRUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA GUANYLYLTRANSFERASE; POLY(A) POLYMERASE; CATALYTIC SUBUNIT; POLYADENYLATION; EXPRESSION; GENE; PURIFICATION; RNA(NUCLEOSIDE-2'-)-METHYLTRANSFERASE; (GUANINE-7-)METHYLTRANSFERASE; METHYLTRANSFERASES AB The vaccinia virus-encoded protein VP39 is a poly(A) polymerase subunit that stimulates the formation of long poly(A) tails as well as a cap-specific mRNA (nucleoside-2'-O-)-methyltransferase. We have carried out mutagenesis studies aimed at locating regions of VP39 which are important for these activities. The open reading frame encoding VP39 was expressed in Escherichia coli as a glutathione S-transferase fusion protein. The affinity-purified protein had both mRNA modification activities, before and after removal of the glutathione S-transferase domain. Truncation, charge cluster --> Ala scanning, and Cys --> Ser substitution mutations of VP39 were made, and the proteins were synthesized, purified, and analyzed. Deletion of the RNA binding domain, experimentally localized within the carboxyl-terminal 112 amino acids, resulted in the loss of both mRNA modification activities. Eleven of the 21 charge cluster --> Ala mutated proteins had low to nondetectable methyltransferase activity. Four of those 11 also lacked adenylyl-transferase stimulatory function, whereas the remainder had amino acid substitutions that selectively affected methyltransferase activity. However, no mutated proteins lacking adenylyltransferase stimulatory function but possessing methyltransferase activity were isolated by the procedures used. Neither of the 2 cysteine residues in VP39 was necessary for either mRNA modification activity. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 35 TC 28 Z9 28 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 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 12 PY 1994 VL 269 IS 32 BP 20700 EP 20706 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB317 UT WOS:A1994PB31700075 PM 8051170 ER PT J AU MARTINO, RL JOHNSON, CA SUH, EB TRUS, BL YAP, TK AF MARTINO, RL JOHNSON, CA SUH, EB TRUS, BL YAP, TK TI PARALLEL COMPUTING IN BIOMEDICAL-RESEARCH SO SCIENCE LA English DT Article ID RECONSTRUCTION; VIRUS AB Scalable parallel computer architectures provide the computational performance needed for advanced biomedical computing problems. The National Institutes of Health have developed a number of parallel algorithms and techniques useful in determining biological structure and function. These applications include processing electron micrographs to determine the three-dimensional structure of viruses, calculating the solvent-accessible surface area of proteins to help predict the three-dimensional conformation of these molecules from their primary structures, and searching for homologous DNA or amino acid sequences in large biological databases. Timing results demonstrate substantial performance improvements with parallel implementations compared with conventional sequential systems. C1 NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP MARTINO, RL (reprint author), NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892, USA. NR 28 TC 32 Z9 32 U1 1 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 AUG 12 PY 1994 VL 265 IS 5174 BP 902 EP 908 DI 10.1126/science.8052847 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB499 UT WOS:A1994PB49900030 PM 8052847 ER PT J AU CORR, M SLANETZ, AE BOYD, LF JELONEK, MT KHILKO, S ALRAMADI, BK KIM, YS MAHER, SE BOTHWELL, ALM MARGULIES, DH AF CORR, M SLANETZ, AE BOYD, LF JELONEK, MT KHILKO, S ALRAMADI, BK KIM, YS MAHER, SE BOTHWELL, ALM MARGULIES, DH TI T-CELL RECEPTOR-MHC CLASS-I PEPTIDE INTERACTIONS - AFFINITY, KINETICS, AND SPECIFICITY SO SCIENCE LA English DT Article ID SURFACE-PLASMON RESONANCE; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; BINDING; COMPLEX; ANTIGEN; MOLECULE; RECOGNITION; PROTEINS; ANTISERA AB The critical discriminatory event in the activation of T lymphocytes bearing alpha beta T cell receptors (TCRs) is their interaction with a molecular complex consisting of a peptide bound to a major histocompatibility complex (MHC)-encoded class I or class II molecule on the surface of an antigen-presenting cell. The kinetics of binding were measured of a purified TCR to molecular complexes of a purified soluble analog of the murine MHC class I molecule H-2L(d) (sH-2L(d)) and a synthetic octamer peptide p2CL in a direct, real-time assay based on surface plasmon resonance. The kinetic dissociation rate of the MHC-peptide complex from the TCR was rapid (2.6 x 10(-2) second(-1), corresponding to a half-time for dissociation of approximately 27 seconds), and the kinetic association rate was 2.1 x 10(5) M(-1) second(-1). The equilibrium constant for dissociation was approximately 10(-7) M. These values indicate that TCRs must interact with a multivalent array of MHC-peptide complexes to trigger T cell signaling. C1 NIAID,MOLEC BIOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT BIOL,NEW HAVEN,CT 06520. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 30 TC 289 Z9 298 U1 0 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 12 PY 1994 VL 265 IS 5174 BP 946 EP 949 DI 10.1126/science.8052850 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB499 UT WOS:A1994PB49900040 PM 8052850 ER PT J AU MANSOUR, SJ MATTEN, WT HERMANN, AS CANDIA, JM RONG, S FUKASAWA, K VANDEWOUDE, GF AHN, NG AF MANSOUR, SJ MATTEN, WT HERMANN, AS CANDIA, JM RONG, S FUKASAWA, K VANDEWOUDE, GF AHN, NG TI TRANSFORMATION OF MAMMALIAN-CELLS BY CONSTITUTIVELY ACTIVE MAP KINASE KINASE SO SCIENCE LA English DT Article ID PROTEIN S6 KINASE; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; XENOPUS-OOCYTES; PHOSPHORYLATION; MOS; ACTIVATION; CASCADE; INVITRO; RAS AB Mitogen-activated protein (MAP) kinase kinase (MAPKK) activates MAP kinase in a signal transduction pathway that mediates cellular responses to growth and differentiation factors. Oncogenes such as ras, src, raf, and mos have been proposed to transform cells by prolonging the activated state of MAPKK and of components downstream in the signaling pathway. To test this hypothesis, constitutively active MAPKK mutants were designed that had basal activities up to 400 times greater than that of the unphosphorylated wild-type kinase. Expression of these mutants in mammalian cells activated AP-1-regulated transcription. The cells formed transformed foci, grew efficiently in soft agar, and were highly tumorigenic in nude mice. These findings indicate that constitutive activation of MAPKK is sufficient to promote cell transformation. C1 UNIV COLORADO,HOWARD HUGHES MED INST,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. UNIV COLORADO,DEPT MOLEC CELLULAR & DEV BIOL,BOULDER,CO 80309. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM48521] NR 51 TC 1236 Z9 1253 U1 0 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 12 PY 1994 VL 265 IS 5174 BP 966 EP 970 DI 10.1126/science.8052857 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB499 UT WOS:A1994PB49900047 PM 8052857 ER PT J AU SAMUELS, DS SHIMIZU, Y NAKABAYASHI, T SHIMIZU, Y AF SAMUELS, DS SHIMIZU, Y NAKABAYASHI, T SHIMIZU, Y TI PHOSPHORYLATION OF DNA TOPOISOMERASE-I IS INCREASED DURING THE RESPONSE OF MAMMALIAN-CELLS TO MITOGENIC STIMULI SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE DNA TOPOISOMERASE I; PHOSPHORYLATION; 12-O-TETRADECANOYLPHORBOL 13-ACETATE; TPA; EPIDERMAL GROWTH FACTOR; INSULIN; CAMPTOTHECIN; (FIBROBLAST); (HEPATOMA CELL); (MOUSE) ID PROTEIN-KINASE-C; SCLERODERMA PATIENTS; GENETIC-EVIDENCE; PHORBOL-ESTER; CALF THYMUS; SIGNAL TRANSDUCTION; REGENERATING LIVER; NUCLEAR-MEMBRANE; TUMOR PROMOTERS; LEUKEMIA-CELLS AB DNA topoisomerase I is phosphorylated after mitogenic stimulation of 3T3-L1 mouse fibroblasts by 12-O-tetradecanoylphorbol 13-acetate (TPA), a phorbol ester tumor promoter. In vivo labeling with [P-32]orthophosphate and immunoprecipitation with an anti-DNA topoisomerase I antibody has demonstrated an increase in the phosphorylation of DNA topoisomerase I in Swiss/3T3 mouse fibroblasts treated with epidermal growth factor (EGF) and H35 rat hepatoma cells treated with insulin. The only phosphorylated form of DNA topoisomerase I observed was the 100-kDa protein. Digestion of DNA topoisomerase I with trypsin revealed two phosphopeptides. In addition, VT-1, a non-responsive genetic variant of 3T3-L1, and the DNA topoisomerase I inhibitor camptothecin were used to further study TPA-induced DNA topoisomerase I phosphorylation. Our results indicate that the phosphorylation of DNA topoisomerase I may be an ubiquitous response of cultured mammalian cells to mitogenic agents, even in the absence of DNA replication. C1 UNIV ARIZONA,DEPT MOLEC & CELLULAR BIOL,TUCSON,AZ. MUKOGAWA WOMENS UNIV,FAC PHARMACEUT SCI,BIOCHEM LAB,NISHINOMIYA,HYOGO 663,JAPAN. KEIO UNIV,SCH MED,DEPT MOLEC BIOL,SHINJUKU KU,TOKYO 160,JAPAN. RP SAMUELS, DS (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 FU NCI NIH HHS [CA-09213]; NIGMS NIH HHS [GM-24375] NR 61 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD AUG 11 PY 1994 VL 1223 IS 1 BP 77 EP 83 DI 10.1016/0167-4889(94)90075-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PD311 UT WOS:A1994PD31100010 PM 8061056 ER PT J AU ROLLER, PP OTAKA, A NOMIZU, M SMYTH, MS BARCHI, JJ BURKE, TR CASE, RD WOLF, G SHOELSON, SE AF ROLLER, PP OTAKA, A NOMIZU, M SMYTH, MS BARCHI, JJ BURKE, TR CASE, RD WOLF, G SHOELSON, SE TI NORLEUCINE AS A REPLACEMENT FOR METHIONINE IN PHOSPHATASE-RESISTANT LINEAR AND CYCLIC-PEPTIDES WHICH BIND TO P85 SH2 DOMAINS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; SOLID-PHASE SYNTHESIS; PHOSPHATIDYLINOSITOL 3-KINASE; TARGETS; ANALOGS; BOC AB A Met residue in the pTyr+3 position has previously been shown to be an important determinant for high affinity binding of peptides to PI 3-kinase p85 SH2 domains. In the present work, a series of linear and cyclic peptides based on the sequence ''Gly-pTyr-Val-Pro-Met-Leu'' as well as analogues having pTyr replaced by the phosphatase-resistant pTyr mimetics, phosphonomethyl phenylalanine (Pmp) or difluorophosphonomethyl phenylalanine (F(2)Pmp), were synthesized and their binding potency in p85 SH2 domain preparations compared with corresponding peptides in which the Met has been substituted by Nle. Nle is a chemically more stable, isosteric Met homologue in which the sulfur has been replaced by a methylene. Significant binding potency was retained by the Nle-containing peptides, indicating that Met is not absolutely essential for high affinity binding to this SH2 domain. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20893. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RI Barchi Jr., Joseph/N-3784-2014 NR 25 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 11 PY 1994 VL 4 IS 15 BP 1879 EP 1882 DI 10.1016/S0960-894X(01)80389-9 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PB556 UT WOS:A1994PB55600019 ER PT J AU PANTALEO, G DEMAREST, JF SOUDEYNS, H GRAZIOSI, C DENIS, F ADELSBERGER, JW BORROW, P SAAG, MS SHAW, GM SEKALY, RP FAUCI, AS AF PANTALEO, G DEMAREST, JF SOUDEYNS, H GRAZIOSI, C DENIS, F ADELSBERGER, JW BORROW, P SAAG, MS SHAW, GM SEKALY, RP FAUCI, AS TI MAJOR EXPANSION OF CD8+ T-CELLS WITH A PREDOMINANT V-BETA USAGE DURING THE PRIMARY IMMUNE-RESPONSE TO HIV SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VARIABLE REGION GENES; CD8+ LYMPHOCYTES-T; VACCINIA VIRUS; EXPRESSION VECTOR; INFECTION; CHAIN; RECOGNITION; SEQUENCES; DIVERSITY AB A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV)(1-4). We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia(2-5). To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain beta-chain (V beta) families. Cells expressing the expanded V beta s predominantly expressed the CD8 T-cell differentiation antigen and mediated HIV-specific cytotoxicity. Major oligoclonal expansions of these CD8(+) T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection. C1 INST RECH CLIN MONTREAL, IMMUNOL LAB, MONTREAL H2W 1R7, PQ, CANADA. PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21702 USA. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. Scripps Res Inst, DEPT NEUROPHARMACOL, DIV VIROL, LA JOLLA, CA 92037 USA. UNIV MONTREAL, DEPT MICROBIOL & IMMUNOL, MONTREAL H3C 3J7, PQ, CANADA. MCGILL UNIV, DEPT MICROBIOL & IMMUNOL, MONTREAL H3A 2B4, PQ, CANADA. RP PANTALEO, G (reprint author), NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 26 TC 548 Z9 558 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 AUG 11 PY 1994 VL 370 IS 6489 BP 463 EP 467 DI 10.1038/370463a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB407 UT WOS:A1994PB40700057 PM 8047166 ER PT J AU KOCISKO, DA COME, JH PRIOLA, SA CHESEBRO, B RAYMOND, GJ LANSBURY, PT CAUGHEY, B AF KOCISKO, DA COME, JH PRIOLA, SA CHESEBRO, B RAYMOND, GJ LANSBURY, PT CAUGHEY, B TI CELL-FREE FORMATION OF PROTEASE-RESISTANT PRION PROTEIN SO NATURE LA English DT Article ID SCRAPIE-ASSOCIATED FORM; CULTURED-CELLS; PRP; CONVERSION; DISEASES; FIBRILS; BIOLOGY; ACID AB THE infectious agent (or 'prion') of the transmissible spongiform encephalopathies (TSEs) such as scrapie resembles a virus in that it replicates in vivo and has distinct strains(1), but it was postulated long ago to contain only protein(2-3). More recently, PrPSc, a pathogenic, scrapie-associated form of the host-encoded prion protein (PrP), was identified as a possible primary TSE agent protein(4-6). PrPSc is defined biochemically by its insolubility and resistance to proteases(7) and is derived post-translationally from normal, protease-sensitive PrP (PrPc)(8,9). The conversion seems to involve conformational change rather than covalent modification(10-13) However, the conversion mechanism and the relationship of PrPSc formation to TSE agent replication remain unclear. Here we report the conversion of PrPc to protease-resistant forms similar to PrPSc in a cell-free system composed of substantially purified constituents. This conversion was selective and required the presence of preexisting PrPSc, providing direct evidence that PrPSc derives from specific PrPc-PrPSc interactions. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 30 TC 701 Z9 722 U1 5 U2 26 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 11 PY 1994 VL 370 IS 6489 BP 471 EP 474 DI 10.1038/370471a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PB407 UT WOS:A1994PB40700059 PM 7913989 ER PT J AU LARMINAT, F BOHR, VA AF LARMINAT, F BOHR, VA TI ROLE OF THE HUMAN ERCC-1 GENE IN GENE-SPECIFIC REPAIR OF CISPLATIN-INDUCED DNA-DAMAGE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HAMSTER OVARY CELLS; NUCLEOTIDE EXCISION REPAIR; INTERSTRAND CROSS-LINKS; PIGMENTOSUM GROUP-F; ESCHERICHIA-COLI; ABC EXCINUCLEASE; CHO CELLS; ADDUCTS; EXTRACTS; YEAST AB The human excision repair gene ERCC-1 gene restores normal resistance to UV and mitomycin C in excision repair deficient chinese hamster ovary cells of complementation group 1. To investigate the involvement of the ERCC-1 gene in gene-specific repair of bulky lesions, we have studied the removal of damage induced by the antitumor agent cisplatin in CHO mutant 43-3B cells of group 1, with or without transfection with the ERCC-1 gene. Firstly, we determined the contribution of the ERCC-1 gene to the repair of interstrand crosslinks (ICL) induced by cisplatin and found efficient removal of ICLs from the dihydrofolate reductase (DHFR) gene in the ERCC-1 transfected 43-3B cells. We then assessed the contribution of ERCC-1 to the repair of intrastrand adducts (IA) induced by cisplatin. Compared to the wild-type parental cell line, the ERCC-1 transfected 43-3B cells repaired the IAs in the DHFR gene inefficiently. Thus, our data suggest that the ERCC-1 gene is more involved in the repair of interstrand crosslinks than in the removal of intrastrand adducts. C1 NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. NR 33 TC 54 Z9 55 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 11 PY 1994 VL 22 IS 15 BP 3005 EP 3010 DI 10.1093/nar/22.15.3005 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD657 UT WOS:A1994PD65700021 PM 8065913 ER PT J AU LEEM, SH ROPP, PA SUGINO, A AF LEEM, SH ROPP, PA SUGINO, A TI THE YEAST SACCHAROMYCES-CEREVISIAE DNA-POLYMERASE-IV - POSSIBLE INVOLVEMENT IN DOUBLE-STRAND BREAK DNA-REPAIR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MEIOTIC RECOMBINATION; EXCISION REPAIR; CHROMOSOME-III; MATING-TYPE; PROBABLE HOMOLOG; S-CEREVISIAE; CDC2 GENE; REPLICATION; BETA; PURIFICATION AB We identified and purified a new DNA polymerase (DNA polymerase IV), which is similar to mammalian DNA polymerase beta, from Saccharomyces cerevisiae and suggested that it is encoded by YCR14C (POLX) on chromosome III. Here, we provided a direct evidence that the purified DNA polymerase IV is indeed encoded by POLX. Strains harboring a pol4 deletion mutation exhibit neither mitotic growth defect nor a meiosis defect, suggesting that DNA polymerase IV participates in nonessential functions in DNA metabolism. The deletion strains did not exhibit UV- sensitivity. However, they did show weak sensitivity to MMS-treatment and exhibited a hyper-recombination phenotype when intragenic recombination was measured during meiosis. Furthermore, MAT alpha pol4 Delta segregants had a higher frequency of illegitimate mating with a MAT alpha tester strain than that of wild-type cells. These results suggest that DNA polymerase IV participates in a double-strand break repair pathway. A 3.2kb of the POL4 transcript was weakly expressed in mitotically growing cells. During meiosis, a 2.2 kb POL4 transcript was greatly induced, while the 3.2 kb transcript stayed at constant levels. This induction was delayed in a swi4 Delta strain during meiosis, while no effect was observed in a swi6 Delta strain. C1 OSAKA UNIV,MICROBIAL DIS RES INST,DEPT MOLEC IMMUNOL,SUITA,OSAKA 565,JAPAN. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 47 TC 48 Z9 53 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 11 PY 1994 VL 22 IS 15 BP 3011 EP 3017 DI 10.1093/nar/22.15.3011 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD657 UT WOS:A1994PD65700022 PM 8065914 ER PT J AU MARAIA, RJ SASAKITOZAWA, N DRISCOLL, CT GREEN, ED DARLINGTON, GJ AF MARAIA, RJ SASAKITOZAWA, N DRISCOLL, CT GREEN, ED DARLINGTON, GJ TI THE HUMAN Y4 SMALL CYTOPLASMIC RNA GENE IS CONTROLLED BY UPSTREAM ELEMENTS AND RESIDES ON CHROMOSOME-7 WITH ALL OTHER HY SCRNA GENES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; YEAST ARTIFICIAL CHROMOSOMES; SS-A ANTIGEN; DNA-SEQUENCES; HUMAN GENOME; SMALL RIBONUCLEOPROTEINS; RO RIBONUCLEOPROTEINS; HEART-BLOCK; PSEUDOGENES; CELLS AB Ro ribonucleoproteins (RNP) constitute a class of evolutionarily conserved small cytoplasmic (sc) RNPs whose functions are unknown. In human cells four distinctive scRNAs designated hY1, hY3, hY4 and hY5 are synthesized by RNA polymerase III (poi III) and accumulate as components of Ro scRNPs. The previously isolated hY1 and hY3 genes contain upstream sequences similar to the class III promoters for Us and 7SK snRNAs. Additional mammalian Y scRNA genes have been refractory to cloning due to interference from numerous hY-homologous pseudogenes and studies of hY RNA genes have been sparse. Although homologs of hY1 and hY3 RNAs exist in rodent cells, the smaller Y4 and Y5 RNAs do not which has allowed us to localize the hY4 scRNA gene to human chromosome 7 by assaying for its transcript in rodent X human somatic cell hybrids (SCH). A chromosome 7-enriched yeast artificial chromosome (YAC) library was then screened and the authentic hY4 sequence was isolated by strepavidin - biotin-mediated hybrid-selection followed by poly(dA)-tailing and hemispecific PCR. The region upstream of the hY4 sequence contains a TATAAAA motif centered at - 26, a candidate proximal sequence element at - 63, and three octamer-like sequences located between - 260 and - 200. hY4 RNA is readily detectable on Northern blots after transient transfection of the hY4 gene into mouse cells but not after transfection of a construct in which the 5' flanking region was deleted. SCHs and chromosome 7-enriched YACs were used to demonstrate that all four hY RNA genes reside on human chromosome 7. C1 WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. TEXAS CHILDRENS HOSP,DEPT PATHOL,HOUSTON,TX 77030. RP MARAIA, RJ (reprint author), NICHHD,MOLEC GROWTH REGULAT LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [P50-HG00201]; NIDDK NIH HHS [DK45285, DK44080] NR 43 TC 27 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 11 PY 1994 VL 22 IS 15 BP 3045 EP 3052 DI 10.1093/nar/22.15.3045 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PD657 UT WOS:A1994PD65700027 PM 7520568 ER PT J AU SCHNEIDER, L GEHA, R AF SCHNEIDER, L GEHA, R TI OUTBREAK OF HEPATITIS-C ASSOCIATED WITH INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION - UNITED-STATES, OCTOBER-1993 JUNE-1994 (REPRINTED FROM MMWR, VOL 43, PG 505-509, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID INFECTION C1 WALTER REED ARMY INST RES,WASHINGTON,DC. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITED DIS,WASHINGTON,DC. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,OFF BLOOD RES & REVIEW,WASHINGTON,DC. NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD. NHLBI,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA. RP SCHNEIDER, L (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 10 PY 1994 VL 272 IS 6 BP 424 EP 425 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PA278 UT WOS:A1994PA27800006 ER PT J AU VOLBERDING, PA LAGAKOS, SW GRIMES, JM STEIN, DS BALFOUR, HH REICHMAN, RC BARTLETT, JA HIRSCH, MS PHAIR, JP MITSUYASU, RT FISCHL, MA SOEIRO, R AF VOLBERDING, PA LAGAKOS, SW GRIMES, JM STEIN, DS BALFOUR, HH REICHMAN, RC BARTLETT, JA HIRSCH, MS PHAIR, JP MITSUYASU, RT FISCHL, MA SOEIRO, R TI THE DURATION OF ZIDOVUDINE BENEFIT IN PERSONS WITH ASYMPTOMATIC HIV-INFECTION - PROLONGED EVALUATION OF PROTOCOL-019 OF THE AIDS-CLINICAL-TRIALS-GROUP SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; CD4+ CELL COUNTS; CUBIC MILLIMETER; DOUBLE-BLIND; EFFICACY; COMPLEX; AZT AB Objective.-To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4(+) cell count. Design and Interventions.-Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo. Setting.-University-based and university-affiliate AIDS research clinics participating in AIDS Clinical Trials Group protocol 019. Patients.-A total of 1565 asymptomatic HIV-infected subjects with entry CD4(+) cell counts less than 0.50x10(9)/L (500/mu L). Main Outcome Measure.-Time to progression to AIDS or death. Results.-During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P=.008, .004, .007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P=.002, .08, .04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4(+) cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo. Conclusions.-Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished overtime especially in subjects with entry CD4(+) cell counts less than 0.30x10(9)/L (300/mu L). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NIAID,BETHESDA,MD. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY. DUKE UNIV,MED CTR,DURHAM,NC. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV MIAMI,SCH MED,MIAMI,FL. ALBERT EINSTEIN MONTEFIORE MED CTR,NEW YORK,NY. RP VOLBERDING, PA (reprint author), SAN FRANCISCO GEN HOSP,AIDS PROGRAM,WARD 84,995 POTRERO AVE,SAN FRANCISCO,CA 94110, USA. NR 21 TC 127 Z9 127 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 10 PY 1994 VL 272 IS 6 BP 437 EP 442 DI 10.1001/jama.272.6.437 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PA278 UT WOS:A1994PA27800024 PM 7913730 ER PT J AU BELSHE, RB GRAHAM, BS KEEFER, MC GORSE, GJ WRIGHT, P DOLIN, R MATTHEWS, T WEINHOLD, K BOLOGNESI, DP SPOSTO, R STABLEIN, DM TWADDELL, T BERMAN, PW GREGORY, T IZU, AE WALKER, MC FAST, P AF BELSHE, RB GRAHAM, BS KEEFER, MC GORSE, GJ WRIGHT, P DOLIN, R MATTHEWS, T WEINHOLD, K BOLOGNESI, DP SPOSTO, R STABLEIN, DM TWADDELL, T BERMAN, PW GREGORY, T IZU, AE WALKER, MC FAST, P TI NEUTRALIZING ANTIBODIES TO HIV-1 IN SERONEGATIVE VOLUNTEERS IMMUNIZED WITH RECOMBINANT GP120 FROM THE MN STRAIN OF HIV-1 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLYCOPROTEIN GP120; TYPE-1 HIV-1; GP160; CHIMPANZEES; VACCINE; PROTECTION; INFECTION; IMMUNOGENICITY; PREVENTION AB Objective.-To evaluate the safety and immunogenicity of the MN strain of recombinant gp120 (MN rgpl20) as a vaccine prototype to prevent human immunodeficiency virus (HIV). Design.-Double-blind, randomized, placebo-controlled study with subjects vaccinated at 0, 4, 24, and 48 weeks and followed up through 64 weeks. Setting.-The AIDS Vaccine Evaluation Units in St Louis, Mo, Nashville, Tenn, and Rochester, NY, conducted the clinical study. Laboratory studies were conducted at Duke University, Raleigh, NC; data analysis was done by the Data Coordinating and Analysis Center at the EMMES Corporation, Potomac, Md: Participants.-Fifty-seven persons seronegative for HIV, at low risk for acquiring HIV infection, and 18 to 60 years of age. Interventions.-The MN rgpl20 vaccine was administered to 12 volunteers each in doses of 100 mu g, 300 mu g, or 600 mu g, and 12 volunteers received a combination of 300 mu g of MN rgp1 20 vaccine and 300 mu g of vaccine from rgpl20 of strain IIIB. Nine volunteers received alum adjuvant alone (control). Main Outcome Measures.-Safety was assessed by monitoring lymphocyte subsets, serum creatinine, and liver enzymes. Immunogenicity was measured by enzyme-linked immunosorbent assay using the immunogen and synthetic peptide corresponding to the variable region 3 domain of gp120. Functional antibody assays included CD4 binding blocking; antibody-dependent, cell-mediated cytotoxicity; and neutralization of homologous and heterologous HIV strains. Results.-No severe adverse reactions occurred. In 33 of 48 volunteers, two doses of vaccine induced antibodies that neutralized the homologous strain HIV1/MN. Three doses of vaccine induced antibodies that neutralized MN (in 46 of 48 volunteers), SF-2 (in 45 of 48 volunteers), or IIIB strains of HIV-1 (in 30 of 48 volunteers). Conclusion.-The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response. C1 VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. DUKE UNIV,SCH MED,DEPT SURG,RALEIGH,NC. EMMES CORP,POTOMAC,MD. GENENTECH INC,S SAN FRANCISCO,CA 94080. NIAID,DIV AIDS,BETHESDA,MD 20892. RP BELSHE, RB (reprint author), ST LOUIS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,1402 S GRAND BLVD,ST LOUIS,MO 63104, USA. FU NIAID NIH HHS [AI-05064, AI-05062, AI-05063] NR 23 TC 120 Z9 121 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 10 PY 1994 VL 272 IS 6 BP 475 EP 480 DI 10.1001/jama.272.6.475 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PA278 UT WOS:A1994PA27800030 PM 7913731 ER PT J AU BARASCH, D KRISHNA, MC RUSSO, A KATZHENDLER, J SAMUNI, A AF BARASCH, D KRISHNA, MC RUSSO, A KATZHENDLER, J SAMUNI, A TI NOVEL DMPO-DERIVED C-13-LABELED SPIN TRAPS YIELD IDENTIFIABLE STABLE NITROXIDES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID 5,5-DIMETHYL-1-PYRROLINE N-OXIDE; CENTERED FREE-RADICALS; HUMAN-NEUTROPHILS; QUANTITATIVE ASPECTS; SUPEROXIDE REACTION; OXYL RADICALS; RESONANCE; SYSTEMS; ADDUCTS; SPECTRA AB The nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is the most common spin trap used for studying free radicals, yet its spin adducts are rapidly and irreversibly destroyed by cells. A methyl substitution at the 2-position of DMPO results in the nitrone 2,5,5-trimethyl-1-pyrroline N-oxide (M(3)PO). Radical addition to M(3)PO is expected to produce stable spin adducts; however, they have almost the same N hyperfine splitting (hfs), and, in the absence of a beta-hydrogen, different adducts are not distinguishable. To overcome this limitation, the synthesis of M(3)PO labeled with C-13 at the nitronyl (C-2) or the 2-methyl (alpha or beta to the aminoxyl group in the spin abduct, respectively) has been undertaken. [alpha-C-13]M(3)PO was synthesized from [2-C-13]acetone in a three-step pathway while [beta-C-13]M(3)PO was obtained from DMPO and [C-13]iodomethane. For M(3)PO, the nuclear magnetic moment of C-13 replaces that of the beta-hydrogen of DMPO and provides the additional hfs necessary for spin adduct identification. Primary radicals, such as *CH3, *CO2- and *OH were generated radiolytically, sonolytically, or enzymatically, trapped by [C-13]M(3)PO, and gave rise to nitroxide spin adducts which were identified and their magnetic parameters determined. The [C-13]M(3)PO spin adducts were far more stable than those of DMPO. Moreover, they were less susceptible to cellular-induced destruction. However, the superoxide adduct of M(3)PO was unstable and did not persist. C1 HEBREW UNIV JERUSALEM,SCH MED,DEPT MOLEC BIOL,IL-91120 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,SCH PHARM,DEPT PHARMACEUT CHEM,IL-91120 JERUSALEM,ISRAEL. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 57 TC 22 Z9 22 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 10 PY 1994 VL 116 IS 16 BP 7319 EP 7324 DI 10.1021/ja00095a040 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA PB764 UT WOS:A1994PB76400040 ER PT J AU HAFT, CR TAYLOR, SI AF HAFT, CR TAYLOR, SI TI DELETION OF 343 AMINO-ACIDS FROM THE CARBOXYL-TERMINUS OF THE BETA-SUBUNIT OF THE INSULIN-RECEPTOR INHIBITS INSULIN SIGNALING SO BIOCHEMISTRY LA English DT Article ID TYROSINE KINASE DOMAIN; GROWTH-FACTOR RECEPTOR; PLASMA-MEMBRANE; JUXTAMEMBRANE REGION; MUTANT ALLELES; RAT-LIVER; AUTOPHOSPHORYLATION; PHOSPHORYLATION; GENE; RESISTANCE AB Naturally occurring mutations in the insulin receptor gene that impair the receptor tyrosine kinase activity cause insulin resistance in vivo in a dominant fashion. Previously, two unrelated families have been described that express an insulin receptor with a truncation due to a premature chain termination at codon 1000 (Delta 1000), thereby deleting 343 amino acids from the carboxyl terminus of the beta-subunit. While clinical findings suggest that the truncated receptor does not mediate insulin action in vivo, a recent study suggested that a similarly truncated receptor enhanced insulin sensitivity in transfected cells by augmenting the signaling by endogenous receptors [Sasaoka, T., Takata, Y., Kusari, J., Anderson, C. M., Langlois, W. J., & Olefsky, J. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 4379-4383]. To investigate these paradoxical data, we studied the structure and function of Delta 1000 truncated insulin receptors when expressed in NIH-3T3 cells. We found that, despite the deletion of most of the tyrosine kinase domain and all of the C-terminal domain of the beta-subunit of the insulin receptor, the Delta 1000 mutant receptors were processed normally and were transported to the plasma membrane where they bind insulin with high affinity. Following ligand addition, the truncated receptors are degraded with a normal half-life. However, they fail to undergo insulin-stimulated internalization, do not regulate the phosphorylation of insulin receptor substrate 1, and are unable to mediate an insulin-stimulated increase in DNA synthesis and c-jun and c-fos expression. These results demonstrate that the Delta 1000 truncated receptors, expressed in our in vitro model system, faithfully mirror the in vivo findings that this mutation causes insulin resistance. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 63 TC 8 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 9 PY 1994 VL 33 IS 31 BP 9143 EP 9151 DI 10.1021/bi00197a017 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB763 UT WOS:A1994PB76300017 PM 8049217 ER PT J AU PAULY, GT HUGHES, SH MOSCHEL, RC AF PAULY, GT HUGHES, SH MOSCHEL, RC TI RESPONSE OF REPAIR-COMPETENT AND REPAIR-DEFICIENT ESCHERICHIA-COLI TO 3 O-6-SUBSTITUTED GUANINES AND INVOLVEMENT OF METHYL-DIRECTED MISMATCH REPAIR IN THE PROCESSING OF O-6-METHYLGUANINE RESIDUES SO BIOCHEMISTRY LA English DT Article ID SITE-SPECIFIC MUTAGENESIS; DNA-REPAIR; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; SINGLE O6-ALKYLGUANINE; ADAPTIVE RESPONSE; MAMMALIAN-CELLS; EXCISION REPAIR; HELA-CELLS; O6-METHYLGUANINE; INVIVO AB Plasmids containing a site-specifically incorporated O-6-methyl- (m(6)G), O-6-ethyl- (e(6)G), or O-6-benzylguanine (b(6)G) within the ATG initiation codon of the lacZ' gene were used to transform Escherichia coli that were repair proficient or deficient in one or both of the E. coli O-6-alkylguanine-DNA alkyltransferases, the uvr(ABC) excision repair system, the recA-mediated recombination system, or the methylation-directed mismatch repair system. Colonies were scored phenotypically for adduct-induced mutations. With plasmids containing either e(6)G or b(6)G, the frequency of adduct-induced mutation was low and independent of the repair proficiency of the strain transformed. Plasmids containing an m(6)G residue elicited similar responses in all but the mismatch repair-deficient strain. The generally low mutagenicity of all the O-6-substituted guanines was interpreted as reflecting an adduct-induced arrest of replication of the modified strand while the unmodified complementary strand was replicated normally. Studies of the involvement of mismatch repair in m(6)G mutagenesis showed that m(6)G:T base pairs were more readily processed than m(6)G:C base pairs, indicating that mismatch repair involving m(6)G residues occurs after replication. These data support a model in which the E. coli methylation-directed mismatch repair system diverts plasmids containing promutagenic m(6)G:T base pairs into replication-arrested complexes providing another line of defense against O-6-methylguanine mutagenicity in addition to O-6-alkylguanine-DNA alkyltransferase repair and excision repair mechanisms. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, CHEM CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC MECHANISMS CARCINOGENESIS LABS, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101] NR 62 TC 34 Z9 34 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 9 PY 1994 VL 33 IS 31 BP 9169 EP 9177 DI 10.1021/bi00197a020 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB763 UT WOS:A1994PB76300020 PM 8049220 ER PT J AU MAKHATADZE, GI CLORE, GM GRONENBORN, AM PRIVALOV, PL AF MAKHATADZE, GI CLORE, GM GRONENBORN, AM PRIVALOV, PL TI THERMODYNAMICS OF UNFOLDING OF THE ALL BETA-SHEET PROTEIN INTERLEUKIN-1-BETA SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MOLAR HEAT-CAPACITY; 3-DIMENSIONAL STRUCTURE; FOLDING THERMODYNAMICS; HYDRATION; RESOLUTION; STABILITY; ENTROPY; ENERGY; CHAIN AB The thermal denaturation of interleukin-1 beta in solution has been studied by differential scanning calorimetry at various pH values. It is shown that the thermal transition of interleukin-1 beta is completely reversible below pH 2.5, only partly reversible in the pH range 2.5-3.5, and irreversible above pH 3.5. Analysis of the reversible unfolding of interleukin-1 beta shows that the heat denaturation is well approximated by a two-state transition and is accompanied by a significant increase of heat capacity. The partial heat capacity of denatured interleukin-1 beta is very close to that expected for the completely unfolded protein. This permitted us to assign the thermodynamic characteristics of interleukin-1 beta denaturation to its complete unfolding and to correlate them with structural features of the protein. The contributions of hydrogen bonding and hydrophobic interactions to the stability of interleukin-1 beta are analyzed and compared to those for other globular proteins. It is shown that the Gibbs energy of a hydrogen bond in a beta-sheet structure is greater than in 1 alpha-helices. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU NIGMS NIH HHS [GM48036-01] NR 41 TC 37 Z9 37 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 9 PY 1994 VL 33 IS 31 BP 9327 EP 9332 DI 10.1021/bi00197a037 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB763 UT WOS:A1994PB76300037 PM 8049234 ER PT J AU YAMAMOTO, M SOBUE, G LI, M MITSUMA, T KIMATA, K YAMADA, Y AF YAMAMOTO, M SOBUE, G LI, M MITSUMA, T KIMATA, K YAMADA, Y TI CAMP-DEPENDENT DIFFERENTIAL REGULATION OF EXTRACELLULAR-MATRIX (ECM) GENE-EXPRESSION IN CULTURED RAT SCHWANN-CELLS SO BRAIN RESEARCH LA English DT Note DE EXTRACELLULAR MATRIX; CAMP; GENE EXPRESSION; SCHWANN CELL ID NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR; CYCLIC-AMP; MULTIDOMAIN PROTEIN; FACTOR RECEPTOR; MESSENGER-RNA; FACTOR NGF; CHAIN; LAMININ; ADENOSINE-3',5'-MONOPHOSPHATE AB cAMP-dependent regulation of the steady-state mRNA levels for the ECM components, laminin A, B-1 and B-2 chains, collagen types I, III and IV were examined by Northern blot analysis in cultured rat Schwann cells. ECM mRNAs of laminin B-1 chain and collagen types I and IV were expressed at high levels in the control Schwann cells, while laminin B-2 chain and collagen type III mRNA levels were low, and laminin A chain mRNA was not detectable. When Schwann cells were treated with forskolin or cAMP derivatives, the gene expression for the ECM molecules constituting the Schwann cell basement membrane, laminin B-1 and B-2 chains, and collagen type IV, was enhanced in time- and dose-dependent manners for exogenously administered forskolin or cAMP derivatives, while the mRNA levels for the ECM molecules, which are not the major components of the basement membrane, fibrillary collagen types I and III were significantly suppressed. This cAMP-dependent differential regulation of Schwann cell ECM gene expression may be related to the role of each ECM molecule in the peripheral nerve development and regeneration. C1 AICHI MED UNIV,DEPT INTERNAL MED 4,DIV NEUROL,AICHI 48011,JAPAN. CHUBU NATL HOSP,DEPT CLIN RES,AICHI 474,JAPAN. AICHI MED UNIV,INST MOLEC SCI MED,AICHI 48011,JAPAN. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. NR 32 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 8 PY 1994 VL 653 IS 1-2 BP 335 EP 339 DI 10.1016/0006-8993(94)90409-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA PA036 UT WOS:A1994PA03600046 PM 7982070 ER PT J AU BRINGMANN, G HARMSEN, S HOLENZ, J GEUDER, T GOTZ, R KELLER, PA WALTER, R HALLOCK, YF CARDELLINA, JH BOYD, MR AF BRINGMANN, G HARMSEN, S HOLENZ, J GEUDER, T GOTZ, R KELLER, PA WALTER, R HALLOCK, YF CARDELLINA, JH BOYD, MR TI ACETOGENIC ISOQUINOLINE ALKALOIDS .69. BIOMIMETIC OXIDATIVE DIMERIZATION OF KORUPENSAMINE A - COMPLETION OF THE FIRST TOTAL SYNTHESIS OF MICHELLAMINE-A, MICHELLAMINE-B, AND MICHELLAMINE-C SO TETRAHEDRON LA English DT Article ID ANCISTROCLADUS AB A first synthetic access to michellamine A (1), a C-2-symmetric antiviral naturally occurring quateraryl, is described, by oxidative 'dimerization' of an appropriately protected 'monomeric' naphthylisoquinoline alkaloid, named korupensamine A (2). Due to the synthetic availability of 2 recently achieved and given the published interconversion of michellamines A - C, this coupling reaction simultaneously represents the completion of a first total synthesis of a representative and thus of all hitherto known michellamines. C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RP BRINGMANN, G (reprint author), UNIV WURZBURG,INST ORGAN CHEM,AM HUBLAND,D-97074 WURZBURG,GERMANY. NR 15 TC 55 Z9 55 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD AUG 8 PY 1994 VL 50 IS 32 BP 9643 EP 9648 DI 10.1016/S0040-4020(01)85532-0 PG 6 WC Chemistry, Organic SC Chemistry GA PB704 UT WOS:A1994PB70400006 ER PT J AU GUSTAFSON, KR BOKESCH, HR FULLER, RW CARDELLINA, JH KADUSHIN, MR SOEJARTO, DD BOYD, MR AF GUSTAFSON, KR BOKESCH, HR FULLER, RW CARDELLINA, JH KADUSHIN, MR SOEJARTO, DD BOYD, MR TI CALANONE, A NOVEL COUMARIN, FROM CALOPHYLLUM-TEYSMANNII SO TETRAHEDRON LETTERS LA English DT Article AB During a survey of latex samples of Calophyllum teysmannii for anti-HIV coumarins (calanolide A, costatolide), calanone (5), an unprecedented benzoyl substituted coumarin, was isolated and its structure determined by spectroscopic analyses. The known soulattrolide (3), and the related ketone 4 were also isolated. Soulanrolide inhibited the cytopathic effect of in vitro HIV-1 infection, while calanone (5) and the ketone 4 were inactive. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 9 TC 31 Z9 32 U1 0 U2 3 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 AUG 8 PY 1994 VL 35 IS 32 BP 5821 EP 5824 DI 10.1016/S0040-4039(00)78193-7 PG 4 WC Chemistry, Organic SC Chemistry GA PA845 UT WOS:A1994PA84500019 ER PT J AU BANERJEEBASU, S BUONANNO, A AF BANERJEEBASU, S BUONANNO, A TI ISOLATION AND STRUCTURE OF THE RAT GENE ENCODING TROPONIN I-SLOW SO GENE LA English DT Note DE SKELETAL MUSCLE; MYOGENESIS; CONTRACTILE PROTEINS; FIBER-TYPE; MINI-EXON ID SKELETAL-MUSCLE; MESSENGER-RNAS; EXPRESSION; CDNA AB Troponin I is a myofibrillar protein involved in the Ca2+-mediated regulation of actomyosin ATPase activity. We report here the isolation and characterization of the gene coding for the slow-muscle-specific isoform of the rat troponin I polypeptide (TpnI). Using restriction mapping, PCR mapping and partial DNA sequencing, we have determined the exon/intron arrangement of this gene. The transcription unit is 10.5-kb long and contains nine exons ranging in size from 4 bp to 330 bp. The rat TpnI(slow) gene is interrupted by large intervening sequences; a 3.3-kb intron separates the 5' untranslated exons from the protein-coding exons. Comparison of the structure of rat TpnI(slow) with that of quail TpnI(fast) reveals that they have a similar intron/exon organization. The 5' untranslated region of the rat gene contains an additional exon, otherwise, the positions of introns and coding exons map to essentially identical regions in both genes, C1 NIH,DEV NEUROBIOL LAB,MOLEC NEUROBIOL UNIT,BETHESDA,MD 20892. 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 0378-1119 J9 GENE JI Gene PD AUG 5 PY 1994 VL 145 IS 2 BP 241 EP 244 DI 10.1016/0378-1119(94)90013-2 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA PB581 UT WOS:A1994PB58100013 PM 8056338 ER PT J AU ELKHARROUBI, A VERDIN, E AF ELKHARROUBI, A VERDIN, E TI PROTEIN-DNA INTERACTIONS WITHIN DNASE I-HYPERSENSITIVE SITES LOCATED DOWNSTREAM OF THE HIV-1 PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCIBLE ENHANCER ELEMENT; T-CELL ACTIVATION; TRANSCRIPTION FACTOR; GENE-EXPRESSION; BINDING-PROTEINS; C-MYC; INITIATION SITE; NUCLEAR FACTOR; MMTV PROMOTER AB We have examined by in vitro footprinting a region located downstream of the human immunodeficiency virus, type 1 (HIV-1) promoter found to be hypersensitive to DNase I digestion in vivo. Recognition sites for several constitutive or inducible DNA binding factors were identified. Three AP-1 binding sites and an AP-3-like motif were situated within the R-U5 region of the long terminal repeat. A novel purine-rich motif (5-GAAAGC-GAAAGDD- 3' (D represents G, A, or T residues)), which interacts with a nuclear factor designated downstream binding factor 1 (DBF1), and two juxtaposed Sp-1 binding sites were located in the untranslated sequence immediately downstream of the 5'-long terminal repeat. Genomic footprinting of these sequence elements in the HIV-1 chronically infected cell lines revealed that the DBF1 and Sp-1 sites are occupied in vivo. Furthermore, transient transfection assays showed that point mutations in the DBF1 binding site decreased significantly the HIV-1 basal promoter activity. Taken together, these results suggest that the DBF1 play a role in the HIV-1 transcription regulation. C1 NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RP ELKHARROUBI, A (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 337,BETHESDA,MD 20892, USA. OI Verdin, Eric/0000-0003-3703-3183 NR 55 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 1994 VL 269 IS 31 BP 19916 EP 19924 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA126 UT WOS:A1994PA12600041 PM 8051074 ER PT J AU HARRISON, KA DRUEY, KM DEGUCHI, Y TUSCANO, JM KEHRL, JH AF HARRISON, KA DRUEY, KM DEGUCHI, Y TUSCANO, JM KEHRL, JH TI A NOVEL HUMAN HOMEOBOX GENE DISTANTLY RELATED TO PROBOSCIPEDIA IS EXPRESSED IN LYMPHOID AND PANCREATIC TISSUES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; DROSOPHILA HOMEOTIC GENES; CELL-SURFACE-ANTIGEN; HUMAN-BONE-MARROW; ANTENNAPEDIA HOMEODOMAIN; TRANSCRIPTION FACTOR; DNA-SEQUENCES; HUMAN PROTEIN; BINDING; DOMAIN AB A novel human homeobox gene, HB9, was isolated from a cDNA library prepared from in vitro stimulated human tonsil B lymphocytes and from a human genomic library. The HB9 gene is composed of 3 exons spread over 6 kilobases of DNA. An open reading frame of 1206 nucleotides is in frame with a diverged homeodomain. The predicted HB9 protein has a molecular mass of 41 kilodaltons and is enriched for alanine, glycine, and leucine. The HB9 homeodomain is most similar to that of the Drosophila melanogaster homeobox gene proboscipedia. Northern blot analysis of poly(A) RNA purified from the human B cell line RPMI 8226 and from activated T cells revealed a major mRNA transcript of 2.2 kilobases. Similar analysis of poly(A) RNA from a variety of adult tissues demonstrated HB9 transcripts in pancreas, small intestine, and colon. Reverse transcriptase-polymerase chain reaction was used to examine HB9 RNA transcripts in hematopoietic cell lines. HB9 RNA transcripts were most prevalent in several human B cell lines and K562 cells. In addition, transcripts were detected in RNA prepared from tonsil B cells and in situ hybridization studies localized them in the germinal center region of adult tonsil. These findings suggest the involvement of HB9 in regulating gene transcription in lymphoid and pancreatic tissues. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 66 TC 64 Z9 66 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 1994 VL 269 IS 31 BP 19968 EP 19975 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA126 UT WOS:A1994PA12600049 PM 7914194 ER PT J AU SYLVESTER, SL APRHYS, CMJ LUETHYMARTINDALE, JD HOLBROOK, NJ AF SYLVESTER, SL APRHYS, CMJ LUETHYMARTINDALE, JD HOLBROOK, NJ TI INDUCTION OF GADD153, A CCAAT ENHANCER-BINDING PROTEIN (C/EBP)-RELATED GENE, DURING THE ACUTE-PHASE RESPONSE IN RATS - EVIDENCE FOR THE INVOLVEMENT OF C/EBPS IN REGULATING ITS EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-PROTEIN; LEUCINE ZIPPER; MESSENGER-RNA; INTERLEUKIN-6; NF-IL6; FAMILY; TRANSCRIPTION; ACTIVATION; ISOFORMS; PROMOTER AB CCAAT/enhancer-binding proteins (C/EBPs) comprise a homologous group of transcriptional regulators that control liver and fat differentiation and are involved in regulating the expression of acute phase reactants during the host response to inflammation. GADD153, a unique member of the C/EBP family, has been proposed to act as a dominant negative inhibitor of other C/EBPs, but little is known about its expression in liver or its role in the processes described above. We have examined its expression during the acute phase response (APR) and have shown that like C/EBP beta and C/EBP delta, GADD153 mRNA is markedly induced in livers of rats treated with lipopolysaccharide to initiate the APR. Interestingly, its induction is temporally delayed relative to that of C/EBP beta and C/EBP delta but is similar to that of acute phase reactants shown to be regulated by C/EBPs. Footprint analysis of the GADD153 promoter showed binding of proteins in liver extracts of both untreated and lipopolysaccharide-injected rats to a putative C/EBP regulatory site. Gel shift analysis showed that although present constitutively, binding activity was increased in extracts from lipopolysaccharide-treated animals. Both C/EBP alpha and C/EBP beta were shown to contribute to the binding activity with the contribution by C/EBP beta increasing during the APR. Support for the functional role of this C/EBP-binding site and its interaction with C/EBPs in regulating GADD153 expression was obtained with cultured HepG2 hepatoma cells in which overexpression of C/EBP beta was found to transactivate expression of a plasmid containing the GADD153 promoter linked to a reporter gene. These findings suggest that the GADD153 gene is itself regulated by C/EBPs during the host response to inflammation and that GADD153 is likely to contribute to the regulation of other genes whose expression is altered during the APR. C1 NIA,GERONTOL RES CTR,GENE EXPRESS & AGING SECT,BALTIMORE,MD 21224. NR 34 TC 84 Z9 85 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 1994 VL 269 IS 31 BP 20119 EP 20125 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA126 UT WOS:A1994PA12600069 PM 8051100 ER PT J AU PAVELKA, MS HAYES, SF SILVER, RP AF PAVELKA, MS HAYES, SF SILVER, RP TI CHARACTERIZATION OF KPST, THE ATP-BINDING COMPONENT OF THE ABC-TRANSPORTER INVOLVED WITH THE EXPORT OF CAPSULAR POLYSIALIC ACID IN ESCHERICHIA-COLI K1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE CHAIN-REACTION; NUCLEOTIDE-BINDING; MALTOSE TRANSPORT; SALMONELLA-TYPHIMURIUM; MULTIDRUG-RESISTANCE; GENE-CLUSTER; PERIPLASMIC PERMEASES; BACTERIAL TRANSPORT; STRUCTURAL MODEL; CYSTIC-FIBROSIS AB The 17-kilobase kps gene cluster of Escherichia coli K1 contains all the information necessary for the expression of capsular polysaccharide. Region 3 of the cluster encodes two genes, kpsM and kpsT, whose products belong to the (A) under bar TP-(B) under bar inding (C) under bar assette (ABC)-transporter protein family. The KpsMT system is involved with the export of capsular polysaccharide in E. coli. Earlier work indicated that interaction between KpsT and ATP is important for transport. In this study, we report that KpsT, a peripheral inner membrane protein, can be photolabeled by the ATP analog, 8-N-3[gamma-P-32]ATP. The derivatiza- tion of KpsT by this reagent is inhibited by cold ATP or ATP gamma S. Furthermore, the protein seems to require a membrane environment for efficient photolabeling, but does not require any other hps gene products. Results obtained from saturation mutagenesis of the ATP-binding consensus sequence of KpsT and the phenotypes of strains with defined mutations in the chromosomal gene, are consistent with the view that ATP-binding by KpsT is required for transport of polymer across the inner membrane. The structure of KpsT was compared to a model developed for other ABC-transport proteins, and important functional regions were determined. The results obtained from chemical mutagenesis of kpsT are consistent with the model and revealed characteristics particular to capsule transporters. C1 UNIV ROCHESTER, MED CTR, DEPT MICROBIOL & IMMUNOL, ROCHESTER, NY 14642 USA. NIAID, ROCKY MT LABS, VECTORS & PATHOGENS LAB, HAMILTON, MT 59840 USA. FU NIAID NIH HHS [5-T32-AI07362, AI26655] NR 68 TC 50 Z9 54 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 5 PY 1994 VL 269 IS 31 BP 20149 EP 20158 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA126 UT WOS:A1994PA12600073 PM 8051103 ER PT J AU MAKHOV, AM HANNAH, JH BRENNAN, MJ TRUS, BL KOCSIS, E CONWAY, JF WINGFIELD, PT SIMON, MN STEVEN, AC AF MAKHOV, AM HANNAH, JH BRENNAN, MJ TRUS, BL KOCSIS, E CONWAY, JF WINGFIELD, PT SIMON, MN STEVEN, AC TI FILAMENTOUS HEMAGGLUTININ OF BORDETELLA-PERTUSSIS - A BACTERIAL ADHESIN FORMED AS A 50-NM MONOMERIC RIGID-ROD BASED ON A 19-RESIDUE REPEAT MOTIF RICH IN BETA-STRANDS AND BETA-TURNS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; ADHESIN; LEUCINE-RICH REPEATS; BETA-HELIX PROTEINS ID RESPIRATORY-EPITHELIAL-CELLS; MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; SECONDARY STRUCTURE; TAIL-FIBER; MOLECULAR-STRUCTURE; ESCHERICHIA-COLI; ADENOVIRUS FIBER; PROMOTING FACTOR; SHEET STRUCTURE AB The filamentous hemagglutinin (FHA) of Bordetella pertussis is an adhesin that binds the bacteria to cells of the respiratory epithelium in whooping-cough infections. Mature FNA is a 220 kDa secretory protein that is highly immunogenic and has been included in acellular vaccines. We have investigated its structure by combining electron microscopy and circular dichroism spectroscopy (CD) with computational analysis of its amino acid sequence. The FHA molecule is 50 nm in length and has the shape of a horseshoe nail: it has a globular head that appears to consist of two domains; a 35 nm-long shaft that averages 4 nm in width, but tapers slightly from the head end; and a small, flexible, tail. Mass measurements by scanning transmission electron microscopy establish that FHA is a monomer. Its sequence contains two regions of tandem 19-residue pseudo-repeats: the first, of 38 cycles, starts at residue 344; the second, of 13 cycles, starts at residue 1440. The repeat motifs are predicted to consist of short beta-strands separated by beta-turns, and secondary structure measurements by CD support this prediction. We propose a hairpin model for FHA in which the head is composed of the terminal domains; the shaft consists mainly of the repeat regions conformed as amphipathic, hyper-elongated beta-sheets, with their hydrophobic faces apposed and the tail is composed of the intervening sequence. Further support for the model was obtained by immuno-labeling electron microscopy. The 19-residue repeats of FHA have features in common with the leucine-rich repeats (LRRs) that are present in many eukaryotic proteins, including some adhesion factors. The model is also compared with the two other classes of filamentous proteins that are rich in beta-structure, i.e. viral adhesins and two beta-helical secretory proteins. Our proposed structure implies how the functionally important adhesion sites and epitopes of PHB are distributed: its tripeptide (RGD) integrin-binding site is assigned to the tail; the putative hemagglutination site forms part of the head. and two classes of immunodominant epitopes are assigned to opposite ends of the molecule. Possible mechanisms are discussed for two modes of FHA-mediated adhesion. C1 NIH,US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOL & ENGN LAB,BETHESDA,MD 20892. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 78 TC 79 Z9 81 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 5 PY 1994 VL 241 IS 1 BP 110 EP 124 DI 10.1006/jmbi.1994.1478 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA947 UT WOS:A1994PA94700012 PM 7519681 ER PT J AU MARAN, A MAITRA, RK KUMAR, A DONG, BH XIAO, W LI, GY WILLIAMS, BRG TORRENCE, PF SILVERMAN, RH AF MARAN, A MAITRA, RK KUMAR, A DONG, BH XIAO, W LI, GY WILLIAMS, BRG TORRENCE, PF SILVERMAN, RH TI BLOCKAGE OF NF-KAPPA-B SIGNALING BY SELECTIVE ABLATION OF AN MESSENGER-RNA TARGET BY 2-5A ANTISENSE CHIMERAS SO SCIENCE LA English DT Article ID ACTIVATED PROTEIN-KINASE; CONSTITUTIVE EXPRESSION; BETA-INTERFERON; RNA; GENE; 2',5'-OLIGOADENYLATE; CELLS; RESISTANCE; INDUCTION; PROMOTER AB Activation of 2-5A-dependent ribonuclease by 5'-phosphorylated, 2',5'-linked oligoadenylates, known as 2-5A, is one pathway of interferon action. Unaided uptake into HeLa cells of 2-5A linked to an antisense oligonucleotide resulted in the selective ablation of messenger RNA for the double-stranded RNA (dsRNA)-dependent protein kinase PKR. Similarly, purified, recombinant human 2-5A-dependent ribonuclease was induced to selectively cleave PKR messenger RNA. Cells depleted of PKR activity were unresponsive to activation of nuclear factor-kappa B (NF-kappa B) by the dsRNA poly(l):poly(C), which provides direct evidence that PKR is a transducer for the dsRNA signaling of NF-kappa B. C1 CLEVELAND CLIN FDN,DEPT CANC BIOL,CLEVELAND,OH 44195. NIDDKD,BIOMED CHEM SECT,BETHESDA,MD 20892. RI Williams, Bryan/A-5021-2009 OI Williams, Bryan/0000-0002-4969-1151 FU NCI NIH HHS [CA 44059]; NIAID NIH HHS [AI 28253, AI 34039-02] NR 37 TC 212 Z9 216 U1 1 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 AUG 5 PY 1994 VL 265 IS 5173 BP 789 EP 792 DI 10.1126/science.7914032 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA372 UT WOS:A1994PA37200035 PM 7914032 ER PT J AU DING, HF RIMSKY, S BATSON, SC BUSTIN, M HANSEN, U AF DING, HF RIMSKY, S BATSON, SC BUSTIN, M HANSEN, U TI STIMULATION OF RNA-POLYMERASE-II ELONGATION BY CHROMOSOMAL PROTEIN HMG-14 SO SCIENCE LA English DT Article ID ASSEMBLED CHROMATIN TEMPLATES; MOBILITY GROUP PROTEIN-14; ACCURATE TRANSCRIPTION; NUCLEOSOMES; GENES; DNA; EXPRESSION; SEQUENCE; INVITRO; CELLS AB The high-mobility group protein 14 (HMG-14) is a non-histone chromosomal protein that is preferentially associated with transcriptionally active chromatin. To assess the effect of HMG-14 on transcription by RNA polymerase II, in vivo-assembled chromatin with elevated amounts of HMG-14 was obtained. Here it is shown that HMG-14 enhanced transcription on chromatin templates but not on DNA templates. This protein stimulated the rate of elongation by RNA polymerase II but not the level of initiation of transcription. These findings suggest that the association of HMG-14 with nucleosomes is part of the cellular process involved in the generation of transcriptionally active chromatin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 FU NIGMS NIH HHS [GM-36667] NR 33 TC 74 Z9 75 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 5 PY 1994 VL 265 IS 5173 BP 796 EP 799 DI 10.1126/science.8047885 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA372 UT WOS:A1994PA37200037 PM 8047885 ER PT J AU RALL, JE AF RALL, JE TI PROOF POSITIVE SO NATURE LA English DT Letter RP RALL, JE (reprint author), NIDDKD,BLDG 10,RM 8N 307,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 4 PY 1994 VL 370 IS 6488 BP 322 EP 322 DI 10.1038/370322c0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA304 UT WOS:A1994PA30400022 PM 8047130 ER PT J AU DOMENE, HM MEIDAN, R YAKAR, S SHENORR, Z CASSORLA, F ROBERTS, CT LEROITH, D AF DOMENE, HM MEIDAN, R YAKAR, S SHENORR, Z CASSORLA, F ROBERTS, CT LEROITH, D TI ROLE OF GI-I AND IGF-I IN THE REGULATION OF IGF-I, IGF-I RECEPTOR AND IGF BINDING-PROTEIN GENE-EXPRESSION IN THE RAT SPLEEN SO REGULATORY PEPTIDES LA English DT Article DE INSULIN-LIKE GROWTH FACTOR; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN; GENE EXPRESSION; MESSENGER-RNA LEVEL; SPLENIC GROWTH ID GROWTH FACTOR-I; HUMAN CULTURED LYMPHOCYTES; RIBONUCLEIC-ACID; DEVELOPMENTAL REGULATION; TISSUE DISTRIBUTION; HORMONAL-REGULATION; MOLECULAR-CLONING; MESSENGER-RNAS; INSULIN; CELLS AB To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 mu g/animal/day), or recombinant human IGF-I (rhIGF-I; 125 mu g/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 +/- 5.6 g (mean +/- S.E.M.) vs. 268.6 +/- 6.0 g; P < 0.001) and spleen weights (0.42 +/- 0.03 g vs. 0.84 +/- 0.06 g; P < 0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 +/- 5.3 g (P < 0.001) after bGH and 213.8 +/- 6.3 g (P < 0.05) after rhIGF-I. Spleen weights were 0.56 +/- 0.048 after bGH P < 0.01 and 0.53 +/- 0.05 g after rhIGF-I (P < 0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 +/- 7.5 % of control values; P < 0.05) and this reduction was prevented by bcH (96.6 +/- 24.2%; NS) but not by rhIGF-I (39.9 +/- 5.0%, NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 +/- 7.4% of control values, P < 0.05) and bGH treatment prevented this reduction (95.5 +/- 12.2%,, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 +/- 3.0%, P < 0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 +/- 15.9% of control values, P < 0.05) and bGH treatment prevented this increase. These data demonstrate that several components of the IGF system are expressed in rat spleen and that following hypophysectomy, there is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioavailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 gene expression. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 48 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 EI 1873-1686 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 4 PY 1994 VL 52 IS 3 BP 215 EP 226 DI 10.1016/0167-0115(94)90056-6 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PC317 UT WOS:A1994PC31700008 PM 7528435 ER PT J AU FESEN, MR POMMIER, Y LETEURTRE, F HIROGUCHI, S YUNG, J KOHN, KW AF FESEN, MR POMMIER, Y LETEURTRE, F HIROGUCHI, S YUNG, J KOHN, KW TI INHIBITION OF HIV-1 INTEGRASE BY FLAVONES, CAFFEIC ACID PHENETHYL ESTER (CAPE) AND RELATED-COMPOUNDS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE HIV; AIDS; INTEGRASE; FLAVONE; CAFFEIC ACID ESTERS ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAMMALIAN TOPOISOMERASE-II; DNA CLEAVAGE; ACCEPTOR OXIDOREDUCTASE; SEQUENCE REQUIREMENTS; REVERSE-TRANSCRIPTASE; GENE-EXPRESSION; RNA-POLYMERASES; CELLULAR DNA; RAT-LIVER AB The inhibition of HIV-1 integrase by flavones and related compounds was investigated biochemically and by means of structure-activity relationships. Purified enzyme and synthetic oligonucleotides were used to assay for three reactions catalysed by integrase: (1) processing of 3' termini by cleavage of the terminal dinucleotide; (2) strand transfer, which models the integration step; and (3) ''disintegration,'' which models the reversal of the strand transfer reaction. Inhibitions of all three reactions by flavones generally occurred in parallel, but caffeic acid phenethyl ester (CAFE) appeared to inhibit reaction 2 selectively. CAFE, however, inhibited reactions 1 and 3 effectively when preincubated with the enzyme, suggesting that this compound differs from the flavones primarily in requiring more time to block the enzyme. The core integrase fragment consisting of amino acids 50-212 retained the ability to catalyse reaction 3, and flavones and CAFE retained the ability to inhibit. Hence, the putative zinc-finger region that is deleted in this fragment is probably not the target of inhibition. Inhibition by flavones usually required the presence of at least one ortho pair of phenolic hydroxyl groups and at least one or two additional hydroxyl groups. Potency was enhanced by the presence of additional hydroxyl groups, especially when present in ortho pairs or in adjacent groups of three. Inhibitory activity was reduced or eliminated by methoxy or glycosidic substitutions or by saturation of the 2,3 double bond. These structure-activity findings for flavones were generally concordant with those previously reported for reverse transcriptase and topoisomerase II. These findings are discussed in the context of a review of the effects of flavones on various enzymes, the possible mechanisms of inhibition, and the potential for building upon a general pharmacophore to generate target specificity. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 52 TC 269 Z9 275 U1 0 U2 9 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 AUG 3 PY 1994 VL 48 IS 3 BP 595 EP 608 DI 10.1016/0006-2952(94)90291-7 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC354 UT WOS:A1994PC35400020 PM 7520698 ER PT J AU GREEN, GM GORDIS, L BINGHAM, E ESCHENBACHER, W GORMAN, DW MARCUS, M RILEY, LW SCHAUMBURG, HH SINGER, MT SPENGLER, JD SUTULA, TP TAYLOR, RE BASCOM, R BERG, SW BLANCK, RR BOLTON, HT CORTIVEAU, J DAXON, EG EITZEN, EM EVENSON, ET FAGAN, JG FELDMAN, EL FRIEDMAN, GK FRIEDMAN, MJ FRY, SA FUKUDA, K HAGAR, B HELLER, J HYAMS, C IREY, NS JOHNSON, DL KANG, HK MAGILL, AJ MARLOWE, DH MATTISON, DR MILLER, CS MOHR, SN MURPHY, FM ODONNELL, FL PILLEMER, SR ROSS, D ROSWELL, RH SHAYEVITZ, M SIDELL, FR STRAUS, SE TARVER, RS TERR, AI WADE, JV FOX, MA ROBERTSON, S WOLFE, K ZUSPANN, B GERRITY, T BEACH, PEM CAMP, T CUSTIS, DL ETZEL, RA FERGUSON, JH GRIESEMER, R HALL, WH HARLAN, WR HICKMAN, JG KEHRL, H RAUCH, T SPHAR, RL THACKER, S VENEGAS, TN AF GREEN, GM GORDIS, L BINGHAM, E ESCHENBACHER, W GORMAN, DW MARCUS, M RILEY, LW SCHAUMBURG, HH SINGER, MT SPENGLER, JD SUTULA, TP TAYLOR, RE BASCOM, R BERG, SW BLANCK, RR BOLTON, HT CORTIVEAU, J DAXON, EG EITZEN, EM EVENSON, ET FAGAN, JG FELDMAN, EL FRIEDMAN, GK FRIEDMAN, MJ FRY, SA FUKUDA, K HAGAR, B HELLER, J HYAMS, C IREY, NS JOHNSON, DL KANG, HK MAGILL, AJ MARLOWE, DH MATTISON, DR MILLER, CS MOHR, SN MURPHY, FM ODONNELL, FL PILLEMER, SR ROSS, D ROSWELL, RH SHAYEVITZ, M SIDELL, FR STRAUS, SE TARVER, RS TERR, AI WADE, JV FOX, MA ROBERTSON, S WOLFE, K ZUSPANN, B GERRITY, T BEACH, PEM CAMP, T CUSTIS, DL ETZEL, RA FERGUSON, JH GRIESEMER, R HALL, WH HARLAN, WR HICKMAN, JG KEHRL, H RAUCH, T SPHAR, RL THACKER, S VENEGAS, TN TI THE PERSIAN-GULF EXPERIENCE AND HEALTH SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. UNIV CINCINNATI,COLL MED,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. BAYLOR COLL MED,DEPT MED,CLIN SERV,HOUSTON,TX 77030. DIASABLED AMER VET,WASHINGTON,DC. EMORY UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & ENVIRONM & OCCUPAT HLTH,ATLANTA,GA. CUNY MT SINAI SCH MED,DIV ENVIRONM & OCCUPAT MED,NEW YORK,NY 10029. CORNELL UNIV,COLL MED,DEPT MED,DIV INT MED,NEW YORK,NY. YESHIVA UNIV,ALBERT EINSTEIN COLL MED,CTR NEUROTOXICOL,DEPT NEUROL,NEW YORK,NY. UNIV CALIF BERKELEY,BERKELEY,CA. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,ENVIRONM SCI & ENGN PROGRAM,BOSTON,MA 02115. UNIV WISCONSIN,SCH MED,DEPT NEUROL,MADISON,WI. HOWARD UNIV,COLL MED,DEPT PHARMACOL,CLIN PHARMACOL PROGRAM,WASHINGTON,DC. VET FOREIGN WARS,WASHINGTON,DC. NATL LEGISLAT COMMISS,AMER LEG,WASHINGTON,DC. DESERT STORM VET ASSOC,HEWITT,TX. US EPA,CLIN RES BRANCH,RES TRIANGLE PK,NC. US DEPT HHS,OFF VET AFFAIRS & MIL LIAISON,WASHINGTON,DC. PARALYZED VET AMER,WASHINGTON,DC. CTR DIS CONTROL & PREVENT,AIR POLLUT & RESP HLTH BRANCH,ATLANTA,GA. NIH,OFF MED APPLICAT RES,BETHESDA,MD. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD. NIEHS,RES TRIANGLE PK,NC. US DEPT DEF,DEPT VET AFFAIRS,ENVIRONM EPIDEMIOL SERV,WASHINGTON,DC. US DEPT DEF,DEPT VET AFFAIRS,COMPENSAT & PENS SERV,WASHINGTON,DC. US DEPT DEF,OFF HLTH AFFAIRS,WASHINGTON,DC. US DEPT DEF,DEPT VET AFFAIRS,WASHINGTON,DC. US DEPT HHS,OFF PUBL AFFAIRS,SPECIAL OUTREACH PROGRAM,WASHINGTON,DC. RI Mattison, Donald/C-2015-2009 NR 0 TC 118 Z9 118 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 3 PY 1994 VL 272 IS 5 BP 391 EP 396 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NY903 UT WOS:A1994NY90300033 ER PT J AU CHOW, WH GRIDLEY, G MCLAUGHLIN, JK MANDEL, JS WACHOLDER, S BLOT, WJ NIWA, S FRAUMENI, JF AF CHOW, WH GRIDLEY, G MCLAUGHLIN, JK MANDEL, JS WACHOLDER, S BLOT, WJ NIWA, S FRAUMENI, JF TI PROTEIN-INTAKE AND RISK OF RENAL-CELL CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIETARY-PROTEIN; CARCINOMA; DISEASE; EPIDEMIOLOGY; KIDNEY; HYPERTENSION; CONSUMPTION; OBESITY; COFFEE AB Background: Penal cell cancer, although still relatively uncommon, has been increasing in incidence in the United States and other countries around the world. Purpose: Since previous studies have suggested an association with high intake of meat, we sought to further examine the role of diet in renal cell cancer risk. Methods: Patients with histologically confirmed renal cell cancer that had been diagnosed between July 1, 1988, and December 31, 1990, were identified through the Minnesota Cancer Surveillance System, a statewide cancer registry. The patients eligible for inclusion in this study were white residents of Minnesota between 20 and 79 years of age. Control subjects were selected from the general population of Minnesota residents; subjects under age 65 were selected by use of a random-digit-dialing method and those 65 years or older were sampled from the Health Care Financing Administration files. Population-based control subjects were frequency-matched to cases by sex and 5-year age groups. A total of 690 patients and 707 control subjects were interviewed. Patients and control subjects were similar in distribution by sex, age, and educational level. Usual adult dietary intakes were assessed by questionnaire, and odds ratios were calculated by logistic regression analyses. Results: Significantly increased risks of renal cell cancer were observed with increasing consumption of several food groups, including red meat (P for trend = .05), high-protein foods (P = .01), and staple (grains, breads, and potatoes) foods (P = .009). When examined by macronutrient status, risks increased monotonically with the amount of protein intake, from 1.2 (95% confidence interval [CI] = 0.7-1.9) to 1.4 (95% CI = 0.8-2.5) and 1.9 (95% CI = 1.0-3.6) (P for trend = .03) in the second, third, and fourth quartiles of intake, respectively, after adjustment for age, sex, caloric intake, body mass index, and cigarette smoking. No significant or consistent associations were detected with the intake of other dietary nutrients or beverages. Conclusion: Although an independent effect of dietary protein has not been previously associated with renal cell cancer, high protein consumption has been related to development of other chronic renal conditions that may predispose an individual to this cancer. Implication: These findings should prompt further study of dietary protein and its potential contribution to the origins of renal cell cancer. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. WESTAT CORP,ROCKVILLE,MD. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 43 TC 66 Z9 66 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 AUG 3 PY 1994 VL 86 IS 15 BP 1131 EP 1139 DI 10.1093/jnci/86.15.1131 PG 9 WC Oncology SC Oncology GA NZ235 UT WOS:A1994NZ23500008 PM 8028035 ER PT J AU MYERS, RB SRIVASTAVA, SS OELSCHLAGER, DK GRIZZLE, WE AF MYERS, RB SRIVASTAVA, SS OELSCHLAGER, DK GRIZZLE, WE TI EXPRESSION OF P160(ERBB-3) AND P185(ERBB-2) IN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATIC ADENOCARCINOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR RECEPTOR; HUMAN-BREAST CANCER; NEU ONCOGENE; BENIGN; OVEREXPRESSION; HYPERPLASIA; HER-2/NEU; C-ERBB-2; CARCINOMA; INDICATOR AB Background: Although prostatic adenocarcinoma is the most frequent malignancy among American men, little is known concerning the roles of growth factors, growth factor receptors, or proto-oncogene products in the development and progression of this malignancy. Purpose: We examined and compared the expression and cellular distribution of the erbB-3 protein (p160(erbB-3)) and the erbB-2 protein (p185(erbB-2)) in various stages of development and progression of prostatic adenocarcinoma. Methods: Immunoperoxidase staining was used to determine the expression of p160(erbB-3) and p185(erbB-2) in benign prostatic epithelium, prostatic intraepithelial neoplasia, localized adenocarcinomas (pathologic stages B and C) as well as matching primary and lymph node lesions from patients with stage D adenocarcinoma. In order to test antibody specificity, we used Western blot analysis to examine the expression of pl60(erbB-3) and p185(erbB-2) in selected prostatic adenocarcinomas. Results: Within benign glands, immunostaining for p160(erbB-3) or p185(erbB-2) mag strongest in the basal cells and was typically absent or weak in the luminal (secretory) cells. Expression of both proteins within luminal cells was localized to cell membranes. We examined the expression of p(160erbB-3) and p185(erbB-2) in the prostatic intraepithelial neoplastic lesions of 22 radical prostatectomy specimens. Like benign glands, the basal cells of these neoplastic lesions typically demonstrated strong to moderate immunostaining when stained with either antibody. In contrast to benign glands, moderate to strong immunostaining for p160(erbB-3) and p185(erbB-2) was frequently observed within the cytoplasm and cell membranes of the prostatic intraepithelial neoplastic luminal cells. p160(erbB-3) and p185(erbB-2) were detected within the malignant cells in 28 and 29 of 29 localized adenocarcinomas, respectively. Immunostaining with either antibody was typically moderate to strong in the malignant cells. Both proteins were expressed on the cellular membranes as well as in the cytoplasm of malignant cells. Immunostaining for p160(erbB-3) was detected in the matching primary and metastatic lesions (lymph nodes) in 10 of 11 patients with stage D adenocarcinoma. carcinoma. Immunostaining for p185(erbB-2) was detected in matching primary and metastatic lesions (lymph nodes) obtained from 16 patients with stage D adenocarcinoma. Western blot analysis confirmed the specificity of the antibodies. Conclusions: These results suggest that increased expression and changes in the subcellular distribution of both p160(erbB-3) and p185(erbB-2) represent early events in the development and progression of prostatic adenocarcinomas. The high expression and distribution of both p160(erbB-3) and p185(erbB-2) are retained both in advanced-stage primary and metastatic tumors. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. FU NCI NIH HHS [N01CN1534002] NR 32 TC 138 Z9 141 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 3 PY 1994 VL 86 IS 15 BP 1140 EP 1145 DI 10.1093/jnci/86.15.1140 PG 6 WC Oncology SC Oncology GA NZ235 UT WOS:A1994NZ23500009 PM 7913137 ER PT J AU ROSENBERG, SA YANNELLI, JR YANG, JC TOPALIAN, SL SCHWARTZENTRUBER, DJ WEBER, JS PARKINSON, DR SEIPP, CA EINHORN, JN WHITE, DE AF ROSENBERG, SA YANNELLI, JR YANG, JC TOPALIAN, SL SCHWARTZENTRUBER, DJ WEBER, JS PARKINSON, DR SEIPP, CA EINHORN, JN WHITE, DE TI TREATMENT OF PATIENTS WITH METASTATIC MELANOMA WITH AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES AND INTERLEUKIN-2 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACTIVATED KILLER CELLS; ESTABLISHED PULMONARY METASTASES; INVIVO ANTITUMOR-ACTIVITY; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; GENE-THERAPY; ADOPTIVE IMMUNOTHERAPY; CYTOKINE SECRETION; NECROSIS-FACTOR; ANTIGENS AB Background: Studies of human tumorinfiltrating lymphocytes (TILs) derived from patients with a variety of histologic types of cancer have demonstrated that cellular immune reactions against established malignancy exist in humans. Purpose: We report the results of using autologous TILs plus high-dose bolus interleukin 2 (IL-2), with or without the concomitant administration of cyclophosphamide, in the treatment of 86 consecutive patients with metastatic melanoma. Methods: From May 1987 through December 1992, 86 patients (38 female and 48 male) with metastatic melanoma were treated (145 courses) with autologous TILs plus high-dose intravenous bolus IL-2 (720000 IU/kg every 8 hours). TILs plus 1L-2 were administered in two cycles separated by approximately 2 weeks. Two treatment cycles constituted one treatment course. Patients received a maximum of 15 doses of IL-2 per cycle given every 8 hours until grade 3 or 4 toxicity was reached that could not easily be reversed by standard supportive measures. All patients received con comitant medications to abrogate some of the side effects of 1L-2 administration: acetaminophen (650 mg every 4 hours), indomethacin (50 mg every 8 hours), and ranitidine (150 mg every 12 hours). Fifty-seven of the 86 patients received a single intravenous dose of 25 mg/kg cyclophosphamide approximately 36 hours before receiving the first intravenous infusion of TILs plus IL-2. Six weeks after treatment, all known sites of disease were evaluated. Results: The overall objective response rate in these patients was 34% and was similar in patients receiving TILs and IL-2 alone (31%) or in conjunction with cyclophosphamide (35%). There was no significant difference in the objective response rate in patients whose therapy with high-dose IL-2 had failed (32%) compared with patients not previously treated with IL-2 (34%). The frequency of response to treatment was greater in those patients who were treated with TILs from younger cultures (P = .0001), TILs with shorter doubling times (P = .03), and TILs that exhibited higher lysis against autologous tumor targets (P = .0008). Patients who received TILs generated from subcutaneous tumor deposits had higher response rates (49%) compared with those receiving TILs from lymph nodes (17%; P = .006). There was one treatment-related death due to respiratory insufficiency. Conclusions: Treatment with TILs and IL-2 with or without cyclophosphamide can result in objective responses in about one third of patients with metastatic melanoma. The side effects of treatment are transient in most patients, and this treatment can be safely administered. These results illustrate the potential value of immune lymphocytes for the treatment of patients with melanoma. RP ROSENBERG, SA (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,RM 2B44,BETHESDA,MD 20892, USA. NR 53 TC 584 Z9 592 U1 5 U2 16 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 3 PY 1994 VL 86 IS 15 BP 1159 EP 1166 DI 10.1093/jnci/86.15.1159 PG 8 WC Oncology SC Oncology GA NZ235 UT WOS:A1994NZ23500012 PM 8028037 ER PT J AU CROPP, CS LIDEREAU, R LEONE, A LISCIA, D CAPPA, APM CAMPBELL, G BARKER, E LEDOUSSAL, V STEEG, PS CALLAHAN, R AF CROPP, CS LIDEREAU, R LEONE, A LISCIA, D CAPPA, APM CAMPBELL, G BARKER, E LEDOUSSAL, V STEEG, PS CALLAHAN, R TI NME1 PROTEIN EXPRESSION AND LOSS OF HETEROZYGOSITY MUTATIONS IN PRIMARY HUMAN BREAST-TUMORS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID GOOD PROGNOSIS; NM23; CANCER; GENE; TRANSFECTION; ASSOCIATION; CARCINOMAS C1 NCI,DIV CANC BIOL DIAG & CTR,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BETHESDA,MD 20892. CTR RENE HUGUENIN,INSERM,ST CLOUD,FRANCE. S GIOVANNI HOSP,TURIN,ITALY. NINCDS,BETHESDA,MD 20892. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 16 TC 34 Z9 34 U1 0 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 AUG 3 PY 1994 VL 86 IS 15 BP 1167 EP 1169 DI 10.1093/jnci/86.15.1167 PG 3 WC Oncology SC Oncology GA NZ235 UT WOS:A1994NZ23500013 PM 8028038 ER PT J AU YAMAZAKI, T BENEDETTI, E KENT, D GOODMAN, M AF YAMAZAKI, T BENEDETTI, E KENT, D GOODMAN, M TI CONFORMATIONAL REQUIREMENTS FOR SWEET-TASTING PEPTIDES AND PEPTIDOMIMETICS SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Review ID ASPARTYL DIPEPTIDE ESTERS; X-RAY CRYSTALLOGRAPHY; METHYL-ESTER; COMPUTER-SIMULATIONS; CRYSTAL-STRUCTURE; RETRO-INVERSO; RECEPTOR-SITE; ACID; ENERGY; STEREOISOMERS C1 UNIV CALIF SAN DIEGO, DEPT CHEM, LA JOLLA, CA 92093 USA. NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. NR 51 TC 43 Z9 45 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD AUG 2 PY 1994 VL 33 IS 14 BP 1437 EP 1451 DI 10.1002/anie.199414371 PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA PA498 UT WOS:A1994PA49800002 ER PT J AU ZHU, ZW DEROSE, EF MULLEN, GP PETERING, DH SHAW, CF AF ZHU, ZW DEROSE, EF MULLEN, GP PETERING, DH SHAW, CF TI SEQUENTIAL PROTON-RESONANCE ASSIGNMENTS AND METAL CLUSTER TOPOLOGY OF LOBSTER METALLOTHIONEIN-1 SO BIOCHEMISTRY LA English DT Article ID RABBIT-LIVER METALLOTHIONEIN-2; NUCLEAR MAGNETIC-RESONANCE; SECONDARY STRUCTURE; H-1-NMR SPECTRA; NMR; SPECTROSCOPY; PROTEINS; EXCHANGE; BINDING; DOMAIN AB NMR studies of Cd-111(6)-MT 1 from lobster have been conducted to determine coordination structure of Cd-thiolate binding in the protein. Sequential proton resonance assignments were made using standard two-dimensional H-1 NMR methods. Two-dimensional H-1-Cd-111 HMQC experiments were then carried out to determine the cadmium-cysteine connectivities in the protein. With this information, it was established that the six Cd ions exist in two different Cd3S9 clusters, each involving three bridging and six terminal thiolate ligands. Sequential cysteines in the sequence provide the sulfhydral ligands for each cluster and do not overlap, as has been found in mammalian metallothionein. Comparison of the N-terminal, Cd3S9 B-type cluster of lobster MT 1 with the Cd3S9 cluster from rabbit MT 2 shows that while eight of the nine cysteine residues occupy homologous positions in their sequences, three of the 12 Cd-thiolate connectivities are different. Similarly, the C-terminal B-cluster of lobster MT 1 was compared with the Cd4S11 cluster of mammalian MT 2, excluding the two terminal cysteine sulfhydryl groups that convert this cluster from A- to B-type. As above, eight of nine cysteine positions are identical, yet five of 12 Cd-sulfhydryl connections are different. These differences are expanded when the role of each cysteine as bridging or terminal ligands in the clusters is considered. C1 UNIV WISCONSIN,DEPT CHEM,MILWAUKEE,WI 53211. UNIV WISCONSIN,NIEHS,MARINE & FRESHWATER BIOMED SCI CTR,MILWAUKEE,WI 53211. FU NIEHS NIH HHS [ES-04184, ES-04026] NR 31 TC 25 Z9 28 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 AUG 2 PY 1994 VL 33 IS 30 BP 8858 EP 8865 DI 10.1021/bi00196a002 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA375 UT WOS:A1994PA37500002 PM 8043573 ER PT J AU LELONG, IH CARDARELLI, CO GOTTESMAN, MM PASTAN, I AF LELONG, IH CARDARELLI, CO GOTTESMAN, MM PASTAN, I TI GTP-STIMULATED PHOSPHORYLATION OF P-GLYCOPROTEIN IN TRANSPORTING VESICLES FROM KB-V1 MULTIDRUG-RESISTANT CELLS SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PLASMA-MEMBRANE GLYCOPROTEIN; HAMSTER LUNG-CELLS; KB CARCINOMA-CELLS; DRUG ACCUMULATION; PHORBOL ESTERS; CANCER-CELLS; HL60 CELLS; ADRIAMYCIN; INHIBITION AB We have previously shown that GTP can replace ATP as an energy source to support vinblastine transport by the multidrug transporter P-glycoprotein (Pgp) in plasma membrane vesicles isolated from the multidrug resistant cell line KB-V1 [Lelong et al. (1992) FEBS Lett. 304, 256-260]. Like [gamma-(32)p] ATP, [gamma-P-32]GTP was also able to phosphorylate Pgp in vitro. Unlabeled GTP enhanced the phosphorylation of the transporter by [gamma-P-32]ATP, whereas unlabeled ATP inhibited incorporation of label. While phosphorylation by [gamma-P-32]ATP was Mg2+-dependent, the enhanced phosphorylation of Pgp by GTP was supported by Mg2+ or Mn2+ and to a lesser extent, Ca2+ Specific inhibitors of cAMP-dependent protein kinase, protein kinase C and cGMP-dependent protein kinase, did not affect phosphorylation. The phosphoprotein phosphatase inhibitor okadaic acid slightly enhanced phosphorylation, and vanadate more dramatically increased phosphorylation of the transporter. Tryptic maps of Pgp phosphorylated peptides indicate that addition of GTP altered the relative labeling of phosphopeptides. These results suggest that the overall phosphorylation of Pgp in vitro is determined by several different protein kinases and phosphatases, at least one of which may be GTP-regulated. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 59 TC 21 Z9 21 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 AUG 2 PY 1994 VL 33 IS 30 BP 8921 EP 8929 DI 10.1021/bi00196a009 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA375 UT WOS:A1994PA37500009 PM 7913830 ER PT J AU CHAN, AML MIKI, T MEYERS, KA AARONSON, SA AF CHAN, AML MIKI, T MEYERS, KA AARONSON, SA TI HUMAN ONCOGENE OF THE RAS SUPERFAMILY UNMASKED BY EXPRESSION CDNA CLONING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION; KINASE; GENES; CELLS; SYSTEM AB As an approach to identify human oncogenes, we generated an expression cDNA library from an ovarian carcinoma line. A potent transforming gene was detected by transfection analysis and identified as TC21, a recently cloned member of the RAS gene superfamily. A single point mutation substituting glutamine for leucine at position 72 was shown to be responsible for activation of transforming properties. While the cDNA clone possessed high transforming activity, the ovarian tumor genomic DNA, which contained the mutated TC21 allele, failed to induce transformed foci. Thus, expression cDNA cloning made it possible to identify and isolate a human oncogene that has evaded detection by conventional approaches. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP CHAN, AML (reprint author), MT SINAI MED CTR,MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,1 GUSTAVE LEVY PL,POB 1130,NEW YORK,NY 10029, USA. NR 27 TC 72 Z9 75 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7558 EP 7562 DI 10.1073/pnas.91.16.7558 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600038 PM 8052619 ER PT J AU LONETTO, MA BROWN, KL RUDD, KE BUTTNER, MJ AF LONETTO, MA BROWN, KL RUDD, KE BUTTNER, MJ TI ANALYSIS OF THE STREPTOMYCES-COELICOLOR SIGE GENE REVEALS THE EXISTENCE OF A SUBFAMILY OF EUBACTERIAL RNA-POLYMERASE SIGMA-FACTORS INVOLVED IN THE REGULATION OF EXTRACYTOPLASMIC FUNCTIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; SEQUENCE-ANALYSIS; CYSTIC-FIBROSIS; TRANSCRIPTION; SUBUNIT; A3(2); DNA; EXPRESSION; REGION AB sigma(E), an RNA polymerase a factor of apparent M(r) 28,000, was previously identified by its ability to direct transcription from the P2 promoter of the agarase gene (dagA) of Streptomyces coelicolor. A degenerate oligonucleotide probe, designed from the N-terminal sequence of purified sigma(E), was used to isolate the sigma(E) gene (sigE). The predicted sequence of sigma(E) shows greatest similarity to sequences of seven other proteins: Myxococcus xanthus CarQ, Pseudomonas aeruginosa AlgU, Pseudomonas syringae HrpL, Escherichia coli sigma(E), Alcaligenes eutrophus CnrH, E. coli FecI, and Bacillus subtilis SigX, a protein of unknown function. These eight proteins define a subfamily of eubacterial RNA polymerase factors sufficiently different from other sigma s that, in many cases, they are not identified by standard similarity searching methods. Available information suggests that all of them regulate extracytoplasmic functions and that they function as effector molecules responding to extracytoplasmic stimuli. A. eutrophus CnrH appears to be a plasmid-encoded factor. C1 JOHN INNES CTR PLANT SCI RES,DEPT GENET,NORWICH NR4 7UH,ENGLAND. UNIV CALIF SAN FRANCISCO,SCH DENT,DEPT STOMATOL,SAN FRANCISCO,CA 94143. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706. UNIV E ANGLIA,SCH BIOL SCI,NORWICH NR4 7TJ,NORFOLK,ENGLAND. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. FU NIGMS NIH HHS [GM36278] NR 35 TC 357 Z9 370 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7573 EP 7577 DI 10.1073/pnas.91.16.7573 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600041 PM 8052622 ER PT J AU EICHHORN, GL CHUKNYISKY, PP BUTZOW, JJ BEAL, RB GARLAND, C JANZEN, CP CLARK, P TARIEN, E AF EICHHORN, GL CHUKNYISKY, PP BUTZOW, JJ BEAL, RB GARLAND, C JANZEN, CP CLARK, P TARIEN, E TI A STRUCTURAL MODEL FOR FIDELITY IN TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RNA SYNTHESIS; RNA POLYMERASE ID COLI RNA-POLYMERASE; RIBONUCLEIC-ACID POLYMERASE; NUCLEAR MAGNETIC-RESONANCE; ESCHERICHIA-COLI; NUCLEOTIDE INCORPORATION; GLUTAMINE-SYNTHETASE; INTRINSIC METAL; BINDING-SITES; ACTIVE-SITE; DNA AB Distances between the metal ions bound to the product terminus i site and the substrate i+ 1 site of Escherichia coli RNA polymerase range from 5.0 to 5.6 Angstrom when the substrate is complementary to a template base and from 6.5 to 7.0 Angstrom for a noncomplementary relationship. The metal bound to the substrate at the i + 1 site exhibits a constant distance to the three phosphates on the substrate regardless of complementarity, but the distance to base and ribose protons changes. The differences in these geometric parameters are explained by the ability of the enzyme to assume two conformations, one to place correct nucleotide substrates in optimal position for bond formation and the other to prevent incorrect nucleotides from assuming such a position. In this scheme a metal-triphosphate complex can move toward or away from the terminal 3' OH group of the growing RNA chain, to assure fidelity of transcription, RP EICHHORN, GL (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 44 TC 7 Z9 7 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7613 EP 7617 DI 10.1073/pnas.91.16.7613 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600049 PM 8052629 ER PT J AU GLADYSHEV, VN KHANGULOV, SV AXLEY, MJ STADTMAN, TC AF GLADYSHEV, VN KHANGULOV, SV AXLEY, MJ STADTMAN, TC TI COORDINATION OF SELENIUM TO MOLYBDENUM IN FORMATE DEHYDROGENASE-H FROM ESCHERICHIA-COLI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SELENOCYSTEINE; SELENOENZYME; MO(V) ELECTRON PARAMAGNETIC RESONANCE SIGNAL; MOLYBDOPTERIN ID SELENOCYSTEINE-CONTAINING POLYPEPTIDE; NUCLEOTIDE-SEQUENCE; ENCODES SELENOCYSTEINE; NITRATE REDUCTASE; XANTHINE-OXIDASE; HYDROGEN-LYASE; GENE-PRODUCT; COFACTORS; CLONING; BIOCHEMISTRY AB Formate dehydrogenase H from Escherichia coli contains multiple redox centers, which include a molybdopterin cofactor, an iron-sulfur center, and a selenocysteine residue (SeCys-140 in the polypeptide chain) that is essential for catalytic activity. Here we show that addition of formate to the native enzyme induces a signal typical of Mo(V) species. This signal is detected by electron paramagnetic resonance (EPR) spectroscopy. Substitution of Se-77 for natural isotope abundance Se leads to transformation of this signal, indicating a direct coordination of Se with Mo. Mutant enzyme with cysteine substituted at position 140 for the selenocysteine residue has decreased catalytic activity and exhibits a different EPR signal. Since determination of the Se content of wild-type enzyme indicates approximate to 1 gram atom per mel, we conclude that it is the Se atom of the SeCys-140 residue in the protein that is coordinated directly with Mo. The amino acid sequence flanking the selenocysteine residue in formate dehydrogenase H is similar to a conserved sequence found in several other prokaryotic molybdopterin-dependent enzymes. In most of these other enzymes a cysteine residue, or in a few cases a serine or a selenocysteine residue, occurs in the position corresponding to SeCys-140 of formate dehydrogenase H. By analogy with formate dehydrogenase H in these other enzymes, at least one of the ligands to Mo should be provided by an amino acid residue of the protein. This ligand could be the Se of a selenocysteine residue, sulfur of a cysteine residue, or, in the case of a serine residue, oxygen. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD 20889. NR 32 TC 67 Z9 68 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7708 EP 7711 DI 10.1073/pnas.91.16.7708 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600068 PM 8052647 ER PT J AU RAZIN, E SZALLASI, Z KAZANIETZ, MG BLUMBERG, PM RIVERA, J AF RAZIN, E SZALLASI, Z KAZANIETZ, MG BLUMBERG, PM RIVERA, J TI PROTEIN-KINASES C-BETA AND C-EPSILON LINK THE MAST-CELL HIGH-AFFINITY RECEPTOR FOR IGE TO THE EXPRESSION OF C-FOS AND C-JUN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; FC(EPSILON) RECEPTOR TYPE I; GENE EXPRESSION ID BASOPHILIC RBL-2H3 CELLS; GENE-EXPRESSION; PHORBOL ESTER; MESSENGER-RNA; TRANSCRIPTION; ACTIVATION; ANTIGEN; PHOSPHORYLATION; ONCOGENE; AP-1 AB In this report we identify the specific isozymes of protein kinase C (PKC) that are involved in c-fos and c-jun mRNA accumulation in the rat basophilic leukemia cell line RBL-2H3. These cells could be largely depleted of the endogenous PKC isozymes by chronic treatment with phorbol 12-myristate 13-acetate followed by permeabilization of the cells with streptolysin O. The reconstitution of these cells with defined concentrations of either PKC-beta or PKC-epsilon up to 10 nM and 20 nM, respectively, induced c-fos and c-jun in a dose-dependent manner. At high concentrations of PKC-beta and -epsilon the induction of c-fos and c-jun was independent of the aggregation of the high-affinity IgE receptors (Fc(epsilon) type I receptors). In contrast, at limiting concentrations of these two PKC isozymes, 1 nM, the increase in c-fos and c-jun mRNAs was dependent on the aggregation of the Fc(epsilon) type I receptors. Unlike PKC-beta and -epsilon, PKC-alpha and PKC-delta failed to reconstitute c-fos and c-jun induction at any dose over the range examined. We conclude that PKC-beta and PKC-epsilon serve as a link between the cell surface receptor and gene expression. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NIAMSD,CHEM IMMUNOL SECT,BETHESDA,MD 20892. RP RAZIN, E (reprint author), HEBREW UNIV JERUSALEM,SCH MED,IL-91120 JERUSALEM,ISRAEL. NR 33 TC 63 Z9 63 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7722 EP 7726 DI 10.1073/pnas.91.16.7722 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600071 PM 8052650 ER PT J AU THOMAS, DC VEAUTE, X KUNKEL, TA FUCHS, RPP AF THOMAS, DC VEAUTE, X KUNKEL, TA FUCHS, RPP TI MUTAGENIC REPLICATION IN HUMAN CELL-EXTRACTS OF DNA CONTAINING SITE-SPECIFIC N-2-ACETYLAMINOFLUORENE ADDUCTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUTATION HOT SPOT; UV-IRRADIATED DNA; ACETYLAMINOFLUORENE ADDUCT; FRAMESHIFT MUTAGENESIS; ESCHERICHIA-COLI; INVITRO; SEQUENCES; TEMPLATES; STRAND; BYPASS AB We have analyzed the effects of site-specific N-2-acetylaminofluorene (AAF) adducts on the efficiency and frameshift fidelity of bidirectional replication of double-stranded DNA in a human cell extract. Plasmid vectors were constructed containing the simian virus 40 origin of replication and single AAF adducts at one of three guanines in the Nar I sequence GGCGCC in a lacZ reporter gene. The presence of an AAF adduct diminishes replication efficiency in HeLa cell extracts by 70-80%. Replication product analyses reveal unique termination sites with each damaged vector, suggesting that when the replication fork encounters an AAF adduct, it often stops before incorporation opposite the adduct. We also observed a higher proportion of products representing replication of the undamaged strand compared to the damaged strand. This suggests that the undamaged strand is replicated more readily, either by uncoupling the first fork to encounter the lesion or by replication using the fork arriving from the other direction. Also included among replication products are covalently closed monomer-length molecules resistant to cleavage at the AAF-modified Nor I site. This resistance is characteristic of substrates containing the AAF adduct, suggesting that translesion bypass had occurred. Transformation of Escherichia coli cells with the replicated damaged DNA yielded lacZ alpha revertant frequencies significantly above values obtained with undamaged DNA or with damaged DNA not replicated in vitro. This increase was only seen with the substrate modified at the third guanine position. Analysis of mutant DNA demonstrated the loss of a GC dinucleotide at the Nar I sequence. Generation of this position-dependent AAF-induced frameshift error in a human replication system is consistent with previous observations in E. coli suggesting that, after incorporation of dCMP opposite modified guanine in the third position, realignment of the template-primer occurs to form an intermediate with two unpaired nucleotides in the template strand. C1 NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. ECOLE SUPER BIOTECHNOL STRASBOURG, CNRS, CANCEROGENESE & MUTAGENESE MOLEC & STRUCT GRP, F-67400 ILLKIRCH GRAFFENSTADEN, FRANCE. NR 20 TC 39 Z9 39 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 AUG 2 PY 1994 VL 91 IS 16 BP 7752 EP 7756 DI 10.1073/pnas.91.16.7752 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600077 PM 8052656 ER PT J AU FARCI, P ALTER, HJ WONG, DC MILLER, RH GOVINDARAJAN, S ENGLE, R SHAPIRO, M PURCELL, RH AF FARCI, P ALTER, HJ WONG, DC MILLER, RH GOVINDARAJAN, S ENGLE, R SHAPIRO, M PURCELL, RH TI PREVENTION OF HEPATITIS-C VIRUS-INFECTION IN CHIMPANZEES AFTER ANTIBODY-MEDIATED IN-VITRO NEUTRALIZATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUTRALIZING ANTIBODIES; POLYMERASE CHAIN REACTION ID NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC NON-A; NATURAL-HISTORY; LONG-TERM; SEQUENCE; HCV; IMMUNITY; GLYCOPROTEIN; VARIABILITY AB Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B hepatitis and is a major cause of chronic liver disease and hepatocellular carcinoma, Development of an effective vaccine would be the most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronically infected patient, and the residual infectivity was evaluated by inoculation of eight seronegative chimpanzees. The source of HCV was plasma obtained from a patient during the acute phase of posttransfusion non-A, non-B hepatitis, which had previously been titered for infectivity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but not with plasma obtained 11 yr later, although both plasmas contained antibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infection. However, the HCV recovered from the patient 2 yr after the infection had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier. This evidence, together with the different sequences of HCV recovered from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experimental evidence in vivo that HCV infection elicits a neutralizing antibody response in humans but suggest that such antibodies are isolate-specific. This result raises concerns for the development of a broadly reactive vaccine against HCV. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV SO CALIF,RANCHO LOS AMIGOS HOSP,DOWNEY,CA 90242. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. BIOQUAL INC,ROCKVILLE,MD 20852. RP FARCI, P (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI-05069] NR 38 TC 383 Z9 394 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7792 EP 7796 DI 10.1073/pnas.91.16.7792 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600085 PM 7519785 ER PT J AU HAYES, JJ PRUSS, D WOLFFE, AP AF HAYES, JJ PRUSS, D WOLFFE, AP TI CONTACTS OF THE GLOBULAR DOMAIN OF HISTONE H5 AND CORE HISTONES WITH DNA IN A CHROMATOSOME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NUCLEOSOME; CHROMATIN; 5S RIBOSOMAL-RNA GENE; XENOPUS ID RIBOSOMAL-RNA GENE; NUCLEOSOME CORE; CRYSTAL-STRUCTURE; LINKER HISTONES; CROSS-LINKING; ORGANIZATION; PAIRS; PARTICLES; BINDING; INVITRO AB The globular domain of histone H5 is found to asymmetrically associate with a nucleosome core including the Xenopus borealis somatic 5S RNA gene. Histones H2A and H2B are required for association of histone H5. Strong crosslinking of the globular domain of histone H5 to the 5S DNA in the nucleosome occurs at a single site to one side of the dyad axis. This site is also in contact with the core histones, and the interactions of the core histones with 5S DNA change as a result of association of the globular domain of histone H5. We discuss evidence for an allosteric change in core histone-5S DNA interactions following the association of the linker histone in the nucleosome. RP HAYES, JJ (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. NR 38 TC 72 Z9 72 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7817 EP 7821 DI 10.1073/pnas.91.16.7817 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600090 PM 8052665 ER PT J AU HANSEN, LA TENNANT, RW AF HANSEN, LA TENNANT, RW TI FOLLICULAR ORIGIN OF EPIDERMAL PAPILLOMAS IN V-HA-RAS TRANSGENIC TG.AC MOUSE SKIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR RECEPTORS; STEM-CELLS; ADHESION MOLECULES; CARCINOGENESIS; CYCLE; MICE; MORPHOGENESIS; INITIATION; FOLLICLES; ANAGEN AB A follicular origin for some skin tumors has been hypothesized in both humans and animal models. Because of its rapid and sensitive response to tumor promoter treatment, a v-Ha-ras transgenic (TG.AC) mouse line was used to determine the origins of epidermal papillomas. Using histological studies and transgene expression as a marker for papilloma development, we determined that pedunculated papillomas arose from focal hyperplasias of the permanent portion of the follicular epithelium in phorbol 12-myristate 13-acetate-treated TG.AC mouse skin. Damage to the hair follicle by depilation was also sufficient to induce papillomas that were histologically indistinguishable from those produced by chemical exposure. Identification of the cellular origins of papillomas in this transgenic mouse model will allow for an analysis of the role of the hair follicle and hair cycle-associated signaling in tumor development. C1 NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 33 TC 72 Z9 72 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 1994 VL 91 IS 16 BP 7822 EP 7826 DI 10.1073/pnas.91.16.7822 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PA376 UT WOS:A1994PA37600091 PM 8052666 ER PT J AU FOWLER, MG AF FOWLER, MG TI PEDIATRIC HIV-INFECTION - NEUROLOGIC AND NEUROPSYCHOLOGIC FINDINGS SO ACTA PAEDIATRICA LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CHILDREN; AIDS RP FOWLER, MG (reprint author), NICHHD,NIAID,DIV AIDS,VACCINE TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD, USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 1994 VL 83 SU 400 BP 59 EP 62 DI 10.1111/j.1651-2227.1994.tb13337.x PG 4 WC Pediatrics SC Pediatrics GA PK300 UT WOS:A1994PK30000016 ER PT J AU HOFF, R MCNAMARA, J FOWLER, MG MCCAULEY, M AF HOFF, R MCNAMARA, J FOWLER, MG MCCAULEY, M TI HIV VACCINE DEVELOPMENT AND CLINICAL-TRIALS SO ACTA PAEDIATRICA LA English DT Article DE CLINICAL TRIALS; HUMAN IMMUNODEFICIENCY VIRUS (HIV); HIV VACCINES; IMMUNE GLOBULIN; VERTICAL TRANSMISSION ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREVENTION; INFECTION AB The magnitude of HIV pandemic has made the development of HIV vaccines an urgent biomedical research priority. Although the biologic problems in designing a vaccine for a chronic viral infection like HIV are formidable, there has been encouraging progress. More than a dozen first generation prophylactic HIV vaccine candidates have completed phase I human trials that have established the safety and immunogenicity of these products in adults. A phase II trial of two HIV subunit envelope vaccines in adults at high risk of HIV infection is underway in the United States, and preparations for phase III efficacy trials have begun. Preliminary studies are under way to evaluate the potential application of active and passive immunization for preventing vertical transmission of HIV. Because of the higher rate of HIV transmission and a more abbreviated time course to disease, it may be more efficient to evaluate the efficacy of HIV vaccines in HIV infected pregnant women and their offspring than in adults who are exposed sexually to HIV. RP HOFF, R (reprint author), NIAID,DIV AIDS,SOLAR BLDG,6003 EXECUTIVE BLVD,ROOM 2B12,ROCKVILLE,MD 20892, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 1994 VL 83 SU 400 BP 73 EP 77 DI 10.1111/j.1651-2227.1994.tb13340.x PG 5 WC Pediatrics SC Pediatrics GA PK300 UT WOS:A1994PK30000019 ER PT J AU MOSS, N AF MOSS, N TI BEHAVIORAL RISKS FOR HIV IN ADOLESCENTS SO ACTA PAEDIATRICA LA English DT Article DE ADOLESCENCE; SEXUAL BEHAVIOR; SUBSTANCE USE; CONDOMS ID SEXUAL-ACTIVITY; CONDOM USE; DRUG-USE; INTERCOURSE; WOMEN; MALES; AIDS AB A psychosocial perspective on adolescent risk behavior is used to highlight aspects of psychological development and social environment that are relevant to sexual activity and substance use. Differences in behavior are also related to factors such as age and gender that have biological, developmental, and demographic implications. Sexual activity and substance use increase during adolescence, and are often interrelated. In the USA in 1992, 69% of 8th graders and 88% of 12th graders had drunk alcohol. In 1990, 54% of high school students had had sexual intercourse. Age of sexual initiation has decreased in recent cohorts, but condom use by adolescents has increased, with 35% of 15-19-year-old women reporting using condoms. Interventions that successfully change adolescent risk behavior take account of the teen's level of development and social context. RP MOSS, N (reprint author), NICHHD,DEMOG & BEHAV SCI BRACH,6100 EXECUT BLVD,ROOM 8B13,BETHESDA,MD 20892, USA. NR 33 TC 0 Z9 0 U1 2 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 1994 VL 83 SU 400 BP 81 EP 87 DI 10.1111/j.1651-2227.1994.tb13342.x PG 7 WC Pediatrics SC Pediatrics GA PK300 UT WOS:A1994PK30000021 ER PT J AU BLANK, A MOFENSON, LM WILLOUGHBY, A YAFFE, SJ AF BLANK, A MOFENSON, LM WILLOUGHBY, A YAFFE, SJ TI MATERNAL AND PEDIATRIC AIDS IN THE UNITED-STATES - THE CURRENT SITUATION AND FUTURE-RESEARCH DIRECTIONS SO ACTA PAEDIATRICA LA English DT Article AB The epidemic of HIV infection and disease in women, adolescents and children represents a complexly intertwined biological and social challenge to health care workers and researchers alike. When considering various issues in confronting this epidemic, women must be viewed as individuals important in their own right, as the primary caretaker of their family members (both infected and uninfected), and as the sexual partners of men who may or may not be infected. Of the myriad of compelling biological questions facing AIDS researchers today, two of the most interesting involve the timing and determinants of vertical transmission and the natural history of HIV infection and disease in women. Scientifically, confronting this epidemic involves research into pathogenesis, epidemiology, natural history, treatment, and prevention of HIV infection. Primary emphasis in the research arena in HIV/AIDS in the United States is focused on therapeutic and prophylactic research. Other research issues are very important, including studies of early diagnostic techniques, behavioral research concerning reproductive choices, the role of breastfeeding in HIV transmission, HIV-specific adolescent issues, and surrogate markers of disease progression. RP BLANK, A (reprint author), NICHHD,BETHESDA,MD 20892, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 0 TC 0 Z9 0 U1 1 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 1994 VL 83 SU 400 BP 106 EP 110 DI 10.1111/j.1651-2227.1994.tb13348.x PG 5 WC Pediatrics SC Pediatrics GA PK300 UT WOS:A1994PK30000027 ER PT J AU CANOSA, CA WILLOUGHBY, A YAFFE, SJ AF CANOSA, CA WILLOUGHBY, A YAFFE, SJ TI HIV-INFECTION IN CHILDREN - FOREWORD SO ACTA PAEDIATRICA LA English DT Editorial Material C1 NICHHD,BETHESDA,MD 20892. RP CANOSA, CA (reprint author), CHILDRENS HOSP LA FE,E-46009 VALENCIA,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 1994 VL 83 SU 400 BP R5 EP R5 PG 1 WC Pediatrics SC Pediatrics GA PK300 UT WOS:A1994PK30000001 ER PT J AU MICHELSON, D MISIEWICZPOLTORAK, B RAYBOURNE, RB GOLD, PW STERNBERG, EM AF MICHELSON, D MISIEWICZPOLTORAK, B RAYBOURNE, RB GOLD, PW STERNBERG, EM TI IMIPRAMINE REDUCES THE LOCAL INFLAMMATORY RESPONSE TO CARRAGEENAN SO AGENTS AND ACTIONS LA English DT Article DE ANTIDEPRESSANTS; IMIPRAMINE; CRH; CORTISOL; INFLAMMATION ID CORTICOTROPIN-RELEASING HORMONE; WALL-INDUCED ARTHRITIS; LEWIS RATS; SUSCEPTIBILITY; EXPRESSION; SECRETION AB Imipramine was administered chronically to LEW/N, outbred and F344/N rats which were then exposed to the aseptic irritant carrageenin in order to determine whether the decreased hypothalamic expression of CRH m-RNA previously shown to be associated with imipramine affects peripheral immune processes. Both LEW/N and outbred but not F344/N rats had vigorous inflammatory responses to carrageenin, and imipramine was associated with significant decreases in the local cellular inflammatory response to carrageenin. Imipramine was also associated with changes in the expression of peripheral blood cell MHC class II expression in LEW/N and outbred rats. These results suggest that at doses comparable to those used clinically imipramine has significant effects on response to an inflammatory stimulus. C1 US FDA,LAUREL,MD 20708. RP MICHELSON, D (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 10 ROOM 3S231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 17 Z9 19 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0065-4299 J9 AGENTS ACTIONS JI Agents Actions PD AUG PY 1994 VL 42 IS 1-2 BP 25 EP 28 DI 10.1007/BF02014295 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA PE662 UT WOS:A1994PE66200007 PM 7847180 ER PT J AU LAKATTA, EG AF LAKATTA, EG TI CARDIOVASCULAR RESERVE CAPACITY IN HEALTHY OLDER HUMANS SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE AGING; ADRENERGIC FUNCTION; CARDIOVASCULAR SYSTEM; CHRONIC PHYSICAL CONDITIONING; LEFT VENTRICULAR RESERVE AB In healthy normotensive individuals who have been rigorously screened to exclude coronary disease, the cardiovascular reserve capacity decreases with aging. A reduction in the maximum aerobic capacity is accompanied by a reduction in the maximum heart rate. Stroke volume during vigorous exercise in the upright position does not decline with aging in healthy individuals, because the left ventricular end-diastolic volume dilates more in older than in younger individuals; however the reduction in left ventricular end-systolic volume that occurs during exercise is blunted in older individuals, resulting in a lesser increase in the left ventricular ejection fraction. This pattern of altered cardiac reserve resembles that caused by beta-adrenergic blockade, and substantial evidence indicates that the efficacy of the beta-adrenergic post synaptic response of cardiovascular tissues declines with aging. Changes in cardiac structure, e.g., enlargement of cardiac myocytes leading to a moderate heart wall thickening, and changes in vascular proper ties, e.g., aortic wall thickening and increased stiffness, also likely have a role in the reduction in left ventricular reserve in older individuals. Chronic exercise conditioning in older individuals increases aerobic capacity, decreases arterial stiffness and left ventricular function. The exercise heart rate deficit that occurs with aging, however is not affected by physical conditioning. RP LAKATTA, EG (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 0 TC 21 Z9 21 U1 0 U2 1 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 AUG PY 1994 VL 6 IS 4 BP 213 EP 223 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PK432 UT WOS:A1994PK43200002 PM 7880870 ER PT J AU OCONNOR, F FLEG, JL GERSTENBLITH, G BECKER, LC GOLDBERG, AP HAGBERG, JM LAKATTA, L LAKATTA, EG SCHULMAN, SP AF OCONNOR, F FLEG, JL GERSTENBLITH, G BECKER, LC GOLDBERG, AP HAGBERG, JM LAKATTA, L LAKATTA, EG SCHULMAN, SP TI EFFECT OF BODY-FAT ON EXERCISE HEMODYNAMICS IN SEDENTARY OLDER MEN SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CARDIAC RESERVE; LEFT VENTRICULAR FUNCTION; OBESITY AB Morbid obesity is often associated with cardiac dilatation and left ventricular dysfunction. The present study investigated whether a similar relationship exists between mild and moderate obesity and left ventricular reserve function in 28 middle aged and older men (58.6+/-6.1 years, mean+/-SD). Subjects had a body mass index of 26.4+/-2.9 kg/m(2), ct percent body fat determined by hydrodensitometry ranging from 9.5% to 33.8%, and were carefully screened to exclude cardiovascular disease. Left ventricular function was assessed by gated blood pool scans at rest and during exhaustive upright cycle exercise. There were no significant relationships between resting or exercise cardiac volumes or ejection fraction with percent body fat; however, peak work rate/kg correlated inversely with percent body fat (r=-0.68, p<0.0001), Heart rate reserve, defined as heart rate at peak work rate minus resting heart rate, declined significantly with increasing percent body fat (r=-0.47, p=O.01). End diastolic volume index reserve also tended to decline with increasing percent body fat, but stroke volume index and cardiac index reserve were maintained because the decrease in end systolic volume index from rest to maximal exercise was greatest in those subjects with highest percent body fat (r=-0.41, p=0.03). Therefore, rest and exercise left ventricular function are not related to percent body fat in healthy older men. However; older more obese men have a smaller increase in heart rate and end diastolic volume and a greater decrease in end systolic volume from rest to peak effort as ct mechanism to augment exercise cardiac output. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. FU NIA NIH HHS [P01-AG-0-4402-10] NR 0 TC 3 Z9 3 U1 0 U2 1 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 AUG PY 1994 VL 6 IS 4 BP 257 EP 265 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PK432 UT WOS:A1994PK43200006 PM 7880874 ER PT J AU LOYA, S BAKHANASHVILI, M TAL, R HUGHES, SH BOYER, PL HIZI, A AF LOYA, S BAKHANASHVILI, M TAL, R HUGHES, SH BOYER, PL HIZI, A TI ENZYMATIC-PROPERTIES OF 2 MUTANTS OF REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (TYROSINE-181 -] ISOLEUCINE AND TYROSINE-188 -] LEUCINE), RESISTANT TO NONNUCLEOSIDE INHIBITORS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TIBO DERIVATIVES; ANGSTROM RESOLUTION; HIV-1 REPLICATION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; DNA; FIDELITY; MUTAGENESIS; RETROVIRUS; EXTENSION AB A number of structurally diverse compounds have been shown to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus (HIV-1) reverse transcriptase (RT). The compounds can be grouped into two broad classes: nucleoside analogs and nonnucleoside inhibitors. The nonnucleoside inhibitors are quite specific for the polymerase activity of HIV-1 RT; they do not affect the polymerase activity of HIV-2 RT or the ribonuclease H (RNase H) activity of either HIV-1 RT or HIV-2 RT. Structural, biochemical, and genetic analyses showed that this group of inhibitors binds in a hydrophobic pocket near the polymerase active site. Mutations in amino acids that line this hydrophobic pocket, for example at tyrosine 181, tyrosine 188, or lysine 103, lead to enzymes that are resistant to the nonnucleoside inhibitors. We have investigated the enzymatic properties of two mutants of HIV-1 RT in which residues 181 and 188 were replaced by the corresponding amino acids in HIV-2 RT (tyrosine 181 --> isoleucine and tyrosine 188 --> leucine). The two tyrosine mutants closely resemble the wild-type HIV-1 RT in almost all the catalytic functions tested, including the heat stability, sensitivity of the DNA polymerase activity to inhibition by deoxynucleoside analogs, inhibition by the zinc chelator o-phenanthroline, and the K-m values calculated for the DNA polymerase activity. There is, however, a slight difference in the effect of orthophenanthroline on the RNase H activity. In addition, there is a subtle disparity in the fidelity of DNA synthesis (analyzed by a mispair extension assay), thus indicating that these mutant RTs are not likely to confer any selective advantages or disadvantages to the variant virions over wildtype virus. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [AI-27035] NR 44 TC 17 Z9 18 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 AUG PY 1994 VL 10 IS 8 BP 939 EP 946 DI 10.1089/aid.1994.10.939 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PE522 UT WOS:A1994PE52200012 PM 7529032 ER PT J AU MASOOD, R LUNARDIISKANDAR, Y JEAN, LFL MURPHY, JR WATERS, C GALLO, RC GILL, P AF MASOOD, R LUNARDIISKANDAR, Y JEAN, LFL MURPHY, JR WATERS, C GALLO, RC GILL, P TI INHIBITION OF AIDS-ASSOCIATED KAPOSIS-SARCOMA CELL-GROWTH BY DAB(389)-INTERLEUKIN-6 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IL-6 SIGNAL TRANSDUCER; LONG-TERM CULTURE; DIPHTHERIA-TOXIN; INTERFERON-ALPHA; FUSION PROTEIN; T-CELLS; INTERLEUKIN-6; RECEPTOR; EXPRESSION; LESIONS AB Acquired immune deficiency syndrome-associated Kaposi's sarcoma (AIDS-KS)-derived spindle cells produce and use interleukin 6 (IL-6) among several other cytokines as a growth factor. In this study we show that AIDS-KS cells express approximately 1100 high-affinity IL-6 receptors (IL-6R) per cell with a dissociation constant (K-d) of 110 pM. Furthermore, AIDS-KS cells express the IL-6R alpha subunit, detected as a single 5.0-kb messenger ribonucleic acid species, and the high-affinity converting, signal-transducing IL-6R beta subunit designated as gp130. Similarly, tumor tissue obtained from patients with KS and AIDS expresses IL-6R messenger ribonucleic acid. We have exploited the chimeric fusion toxin DAB(389)-IL-6, which exerts cellular toxicity only to the cells expressing IL-6R. This chimeric protein was engineered by fusion of a truncated diphtheria toxin structural gene, in which the region encoding the native receptor-binding domain was removed and replaced with the gene encoding IL-6. DAB(389)-IL-6 inhibited protein synthesis in AIDS-KS-derived spindle cells at very low concentrations (IC50 of 3.4 x 10(-11) M). Similarly, inhibition of cell viability by DAB(389)-IL-6 was observed at equivalent dose levels (IC50 of 5 X 10(-11)). These effects on protein synthesis and cell viability can be abrogated by recombinant human IL-6, indicating receptor specificity. Thus, DAB(389)-IL-6 is a potential agent for the treatment of AIDS-associated KS. C1 UNIV SO CALIF,SCH MED,DEPT INTERNAL MED,LOS ANGELES,CA 90033. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,EVANS DEPT CLIN RES,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. SERAGEN INC,HOPKINTON,MA 01748. FU NCI NIH HHS [CA 51621] NR 26 TC 27 Z9 27 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 AUG PY 1994 VL 10 IS 8 BP 969 EP 975 DI 10.1089/aid.1994.10.969 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PE522 UT WOS:A1994PE52200016 PM 7811548 ER PT J AU KAMINCHIK, J MARGALIT, R YAISH, S DRUMMER, H AMIT, B SARVER, N GORECKI, M PANET, A AF KAMINCHIK, J MARGALIT, R YAISH, S DRUMMER, H AMIT, B SARVER, N GORECKI, M PANET, A TI CELLULAR-DISTRIBUTION OF HIV TYPE-1 NEF PROTEIN - IDENTIFICATION OF DOMAINS IN NEF REQUIRED FOR ASSOCIATION WITH MEMBRANE AND DETERGENT-INSOLUBLE CELLULAR MATRIX SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID GENE-PRODUCT; PLASMA-MEMBRANE; SARCOMA-VIRUS; T-CELLS; EXPRESSION; LOCALIZATION; RECEPTOR; AFFINITY; BINDING; PP60V-SRC AB Cellular distribution of HIV-1 Nef protein was studied by expressing the protein in mammalian cells. Cell extracts were fractionated by low- and high-speed centrifugation and by nonionic detergents. Two Nef-related proteins were expressed in COS cells, Nef-27kD and Nef-25kD. Nef-27kD, an N-myristoylated form of Nef, was found in the cytosol and in association with a particulate fraction of the cytoplasm. Treatment of the particulate cytoplasmic fraction with nonionic detergents, using three different protocols designed to isolate the cytoskeleton matrix, indicated that part of Nef was sensitive and part was resistant to detergent solubilization. These two cellular fractions represent membrane- and cytoskeleton-associated Nef. Nef-25kD, initiated from an in-frame AUG codon, was not modified with myristic acid at the amino terminus. Consequently, this protein was present in a soluble form in the cytosol. Furthermore, a mutant of Nef-27kD, in which the myristoylation signal is deleted, appears as a cytoplasmic soluble protein. To determine domains in Nef that are responsible for its subcellular distribution, successive internal deletions of 14-20 amino acids were introduced at the N-terminal portion of the protein. Five mutants were evaluated with respect to their cellular localization. One mutant (pSVLA-5), from which amino acids 73-88 were deleted, did not copurify with the detergent-insoluble fraction. The protein was, however, present in the particulate cytoplasmic fraction, presumably in association with membranes. Taken together, these results suggest that N-myristoylation of Nef affects its association with both membranes and cytoskeleton. Deletion of amino acids 73-88, on the other hand, specifically abolishes the association of Nef with the cytoskeleton matrix. C1 NIAID,DIV AIDS,BASIC RES & DEV PROGRAM,DEV THERAPEUT BRANCH,BETHESDA,MD 20892. RP KAMINCHIK, J (reprint author), BIOTECHNOL GEN LTD,IL-76326 REHOVOT,ISRAEL. NR 26 TC 50 Z9 50 U1 1 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 AUG PY 1994 VL 10 IS 8 BP 1003 EP 1010 DI 10.1089/aid.1994.10.1003 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PE522 UT WOS:A1994PE52200020 PM 7811531 ER PT J AU BASKAR, PV RAY, SC RAO, R QUINN, TC HILDRETH, JEK BOLLINGER, RC AF BASKAR, PV RAY, SC RAO, R QUINN, TC HILDRETH, JEK BOLLINGER, RC TI PRESENCE IN INDIA OF HIV TYPE-1 SIMILAR TO NORTH-AMERICAN STRAINS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Note C1 JOHNS HOPKINS UNIV,DEPT PHARMACOL & MOLEC SCI,DIV INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. APOLLO HOSP,HYDERABAD,INDIA. NIAID,BETHESDA,MD 20892. RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU FIC NIH HHS [43 TW0000]; NCRR NIH HHS [5M01RR00722]; NIAID NIH HHS [AI 33879-02] NR 9 TC 30 Z9 31 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 AUG PY 1994 VL 10 IS 8 BP 1039 EP 1041 DI 10.1089/aid.1994.10.1039 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PE522 UT WOS:A1994PE52200024 PM 7811535 ER PT J AU ABIMIKU, A FRANCHINI, G TARTAGLIA, J ALDRICH, K MYAGKIKH, M MARKHAM, P CHONG, P KLEIN, M KIENY, MP PAOLETTI, E GALLO, R ROBERTGUROFF, M AF ABIMIKU, A FRANCHINI, G TARTAGLIA, J ALDRICH, K MYAGKIKH, M MARKHAM, P CHONG, P KLEIN, M KIENY, MP PAOLETTI, E GALLO, R ROBERTGUROFF, M TI IMMUNE-RESPONSES IN RHESUS MACAQUES PROTECTED AGAINST AN HIV-2 CHALLENGE FOLLOWING VACCINATION WITH ATTENUATED POXVIRUSES CARRYING HIV-1 GENES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. VIROGENET CORP,TROY,NY 12180. ADV BIOSCI LABS,KENSINGTON,MD. CONNAUGHT LABS,N YORK,ON,CANADA. TRANSGENE SA,STRASBOURG,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S45 EP S45 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600098 ER PT J AU AGRAWAL, S TANG, JY SUN, D WEICHOLD, F GALLO, R LISZIEWICZ, J AF AGRAWAL, S TANG, JY SUN, D WEICHOLD, F GALLO, R LISZIEWICZ, J TI GEM-91 - ANTISENSE OLIGONUCLEOTIDE BASED THERAPEUTIC AGENT FOR AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HYBRIDON INC,WORCESTER,MA. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20852. NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S30 EP S30 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600047 ER PT J AU ARTHUR, LO ROSSIO, JL BESS, JW HENDERSON, LE AF ARTHUR, LO ROSSIO, JL BESS, JW HENDERSON, LE TI HIV-ASSOCIATED MHC ANTIGENS - POTENTIAL ROLE IN IMMUNOPATHOGENESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S41 EP S41 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600084 ER PT J AU BARTHOLOMEW, C EDWARDS, J JACK, N WHITE, F CLEGHORN, F BLATTNER, W AF BARTHOLOMEW, C EDWARDS, J JACK, N WHITE, F CLEGHORN, F BLATTNER, W TI STUDIES AND THEORIES ON PATHOGENESIS OF ATL SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 GEN HOSP,PORT OF SPAIN,TRINID & TOBAGO. CARIBBEAN EPIDEMIOL CTR,PORT OF SPAIN,TRINID & TOBAGO. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S111 EP S111 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600332 ER PT J AU BENVENISTE, R AGY, M ARTHUR, L BESS, J COREY, L SCHMIDT, A MORTON, W AF BENVENISTE, R AGY, M ARTHUR, L BESS, J COREY, L SCHMIDT, A MORTON, W TI TITRATION IN PIG-TAILED MACAQUES OF THE HIV-1 III-B CHIMPANZEE VIRUS CHALLENGE STOCK SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,CTR PRIMATE,SEATTLE,WA 98195. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S88 EP S88 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600257 ER PT J AU BENVENISTE, R KULLER, L HU, SL CLARK, M CLERICI, M SHEARER, G MORTON, W AF BENVENISTE, R KULLER, L HU, SL CLARK, M CLERICI, M SHEARER, G MORTON, W TI EXPOSURE TO SUBINFECTIOUS DOSES OF SIV PROTECTS MACAQUES FROM SUBSEQUENT VIRUS CHALLENGE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. WASHINGTON PRIMATE CTR,SEATTLE,WA 98195. NCI,FREDERICK,MD 21702. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S85 EP S85 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600242 ER PT J AU BERMAN, PW NAKAMURA, GR HASTINGS, R WILKES, D FOX, J BYRN, R SCHWARTZ, D BELSHE, R MATTHEWS, T NORCROSS, MA AF BERMAN, PW NAKAMURA, GR HASTINGS, R WILKES, D FOX, J BYRN, R SCHWARTZ, D BELSHE, R MATTHEWS, T NORCROSS, MA TI ANALYSIS OF THE IMMUNOGENICITY OF RECOMBINANT GP120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA. GENENTECH INC,DEPT PHARMACOL,S SAN FRANCISCO,CA. NEW ENGLAND DEACONESS HOSP,DEPT HEMATOL & ONCOL,BOSTON,MA. US FDA,NAIAD,AIDS VACCINE EVALUAT NETWORK,BETHESDA,MD. US FDA,DIV VIROL,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S46 EP S46 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600102 ER PT J AU BERNEMAN, ZN SIMPSON, S READCONNOLE, E LUSSO, P REITZ, MS AF BERNEMAN, ZN SIMPSON, S READCONNOLE, E LUSSO, P REITZ, MS TI GENOMIC STRUCTURE OF HUMAN HERPESVIRUS-7 (HHV-7) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,BIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S123 EP S123 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600373 ER PT J AU BERZOFSKY, JA AHLERS, JD SHIRAI, M PENDLETON, CD TAKESHITA, T DUNLOP, N MINASSIAN, A NEWMAN, M NARA, PL AF BERZOFSKY, JA AHLERS, JD SHIRAI, M PENDLETON, CD TAKESHITA, T DUNLOP, N MINASSIAN, A NEWMAN, M NARA, PL TI CONSTRUCTION OF CANDIDATE SYNTHETIC PEPTIDE VACCINES FOR HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,FREDERICK,MD. PRI,FREDERICK,MD. CAMBRIDGE BIOTECH,WORCESTER,MA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S35 EP S35 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600063 ER PT J AU BIGGAR, RJ HAHN, B TAYLOR, M BLACK, F HJELLE, B NEEL, J AF BIGGAR, RJ HAHN, B TAYLOR, M BLACK, F HJELLE, B NEEL, J TI THE VIRAL ARCHAEOLOGY OF HTLV-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD. UNIV ALABAMA,TUSCALOOSA,AL 35487. YALE UNIV,NEW HAVEN,CT 06520. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. UNIV MICHIGAN,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S113 EP S113 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600339 ER PT J AU BIGGAR, RJ CURTIS, R RABKIN, C COTE, T MELBYE, M AF BIGGAR, RJ CURTIS, R RABKIN, C COTE, T MELBYE, M TI CANCER RISK IN AIDS PATIENTS WITH KAPOSIS-SARCOMA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S55 EP S55 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600135 ER PT J AU BISWAS, P POLI, G FRANZOSO, G SIEBENLIST, U FAUCI, AS AF BISWAS, P POLI, G FRANZOSO, G SIEBENLIST, U FAUCI, AS TI ENDOGENOUS TUMOR-NECROSIS-FACTOR (TNF-A) AND ITS INDUCIBLE FACTOR NF-KB ARE CRITICAL IN THE REGULATION OF HIV-INFECTION IN U937 CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,LIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S75 EP S75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600207 ER PT J AU BLATTNER, W AF BLATTNER, W TI HUMAN RETROVIRUSES - INTERVENTION STRATEGIES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S105 EP S105 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600310 ER PT J AU BLUMENTHAL, R PAK, C KRUMBIEGEL, M DIMITROV, DS PURI, A AF BLUMENTHAL, R PAK, C KRUMBIEGEL, M DIMITROV, DS PURI, A TI INTERACTIONS OF CD4 BEARING PLASMA-MEMBRANE VESICLES WITH GP120-GP41 EXPRESSING CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD. NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S28 EP S28 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600041 ER PT J AU BROWN, K PARK, S KANNO, T FRANZOSO, G SIEBENLIST, U AF BROWN, K PARK, S KANNO, T FRANZOSO, G SIEBENLIST, U TI MUTUAL REGULATION OF THE TRANSCRIPTIONAL ACTIVATOR NF-KAPPA-B AND ITS INHIBITOR, I-KAPPA-B-ALPHA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S96 EP S96 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600281 ER PT J AU BROWNING, PJ SECHLER, JMG ENSOLI, B KAPLAN, M WASHINGTON, RH GENDELMAN, R YARCHOAN, R GALLO, RC AF BROWNING, PJ SECHLER, JMG ENSOLI, B KAPLAN, M WASHINGTON, RH GENDELMAN, R YARCHOAN, R GALLO, RC TI IDENTIFICATION AND CULTURE OF KS-LIKE SPINDLE CELLS FROM THE PERIPHERAL-BLOOD OF HIV-1-INFECTED INDIVIDUALS AND NORMAL CONTROLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MED BRANCH,LTCB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. N SHORE UNIV HOSP,DEPT INTERNAL MED,DIV INFECT DIS & IMMUNOL,MANHASSET,NY 11030. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S51 EP S51 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600121 ER PT J AU BRUGGEMAN, LA ADLER, SH KOPP, JB NOTKINS, AL RAPPAPORT, J KLOTMAN, PE AF BRUGGEMAN, LA ADLER, SH KOPP, JB NOTKINS, AL RAPPAPORT, J KLOTMAN, PE TI BINDING OF HOST TRANSCRIPTIONAL PROTEINS, NF-KB AND SPL, TO THE HIV-1 LTR IN TRANSGENIC MOUSE-TISSUES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S95 EP S95 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600277 ER PT J AU BUONAGURO, L BUONAGURO, FM GALLO, RC ENSOLI, B GIRALDO, G AF BUONAGURO, L BUONAGURO, FM GALLO, RC ENSOLI, B GIRALDO, G TI RESPONSIVE SEQUENCES OF THE TUMOR-NECROSIS-FACTOR-BETA (TNF-BETA) PROMOTER INVOLVED IN THE HIV-1 TAT-MEDIATED TRANSACTIVATION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. IST NAZL TUMORI FOND G PASCALE,NAPLES,ITALY. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S98 EP S98 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600290 ER PT J AU CAFARO, A GIDLUND, M ROBERTGUROFF, M ROSENBERG, Y WIGZELL, H THIELE, C AF CAFARO, A GIDLUND, M ROBERTGUROFF, M ROSENBERG, Y WIGZELL, H THIELE, C TI HIV-1 NEUTRALIZING SERA MEDIATE THE ENHANCEMENT OF VIRAL-INFECTION IN A CD4-NEGATIVE MONOCYTIC CELL CLONE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HENRY M JACKSON FDN,ROCKVILLE,MD. KAROLINSKA INST,DEPT IMMUNOL,S-10401 STOCKHOLM,SWEDEN. NCI,PEDIAT BRANCH,MOLEC GENET SECT,BETHESDA,MD 20892. RI Gidlund, Magnus/C-6408-2008; Cafaro, Aurelio/K-5314-2016 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S73 EP S73 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600201 ER PT J AU CARA, A GUARNACCIA, F GALLO, RC REITZ, MS LORI, F AF CARA, A GUARNACCIA, F GALLO, RC REITZ, MS LORI, F TI DIFFERENT REPLICATION OF HIV-1 INTEGRASE DEFECTIVE MUTANT IN PBL AND MACROPHAGES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,LTCB,BETHESDA,MD. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S97 EP S97 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600287 ER PT J AU CHANG, HK GENDELMAN, R LISZIEWICZ, J GALLO, RC ENSOLI, B AF CHANG, HK GENDELMAN, R LISZIEWICZ, J GALLO, RC ENSOLI, B TI BLOCK OF HIV-1 INFECTION BY A COMBINATION OF ANTISENSE TAT RNA AND TAR DECOYS - A STRATEGY FOR CONTROL OF HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S22 EP S22 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600019 ER PT J AU CHANNAVAJJALA, LS AYUB, J SAXINGER, WC AF CHANNAVAJJALA, LS AYUB, J SAXINGER, WC TI CELL-ADHESION TO HIV-1 TAT IS PREDOMINANTLY MEDIATED THROUGH THE BASIC REGION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S54 EP S54 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600131 ER PT J AU CLERICI, M AXBERG, I POLACINOFIRPO, P KULLER, L MORTON, WR BENVENISTE, RE SHEARER, GM CLARK, EA AF CLERICI, M AXBERG, I POLACINOFIRPO, P KULLER, L MORTON, WR BENVENISTE, RE SHEARER, GM CLARK, EA TI SIV-SPECIFIC IMMUNITY IN MACAQUES EXPOSED INTRARECTALLY TO LOW OR HIGH-DOSES OF SIV/MNE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. ASTRA RES CTR AB,S-15185 SODERTALJE,SWEDEN. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98103. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S85 EP S85 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600244 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI DEVELOPING AN EFFECTIVE AIDS VACCINE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S35 EP S35 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600064 ER PT J AU CONLEY, S MERGES, M NARA, P AF CONLEY, S MERGES, M NARA, P TI NATIVE PARTICLE SUSPENSION ELISA (NPSE) - A NOVEL METHOD FOR STUDYING THE IMMUNOCHEMISTRY OF HIV-1 GP120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BCDP,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,LTCB,VBS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S68 EP S68 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600180 ER PT J AU CONSTANTOULAKIS, P NASIOULAS, G AFONINA, E TURPIN, J CUNNINGHAM, CP HARRISON, J FELBER, BK PAVLAKIS, GN AF CONSTANTOULAKIS, P NASIOULAS, G AFONINA, E TURPIN, J CUNNINGHAM, CP HARRISON, J FELBER, BK PAVLAKIS, GN TI AN INTERFERON-INDUCIBLE GENE FAMILY ENCODES RNA-BINDING PROTEINS THAT INHIBIT REV-MEDIATED HIV-1 EXPRESSION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NR 2 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S94 EP S94 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600273 ER PT J AU DECLUE, JE JOHNSON, MR CEN, H ZHANG, K LOWY, DR AF DECLUE, JE JOHNSON, MR CEN, H ZHANG, K LOWY, DR TI POSITIVE AND NEGATIVE REGULATION OF MAMMALIAN RAS PROTEINS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. AMGEN CORP,THOUSAND OAKS,CA 91320. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S56 EP S56 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600139 ER PT J AU DIGILIO, L SCHLEGEL, R SPARKOWSKI, JJ NAKAMURA, Y ERDOS, M LEONARD, W FRANCHINI, G AF DIGILIO, L SCHLEGEL, R SPARKOWSKI, JJ NAKAMURA, Y ERDOS, M LEONARD, W FRANCHINI, G TI THE BOVINE PAPILLOMAVIRUS-1 (BPV-1) E5 ONCOPROTEIN BINDS TO THE BETA-CHAIN OF THE INTERLEUKIN-2 RECEPTOR (IL-2R) - MAPPING OF THE BETA-CHAIN BINDING DOMAIN SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD. GEORGETOWN UNIV,WASHINGTON,DC 20057. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S57 EP S57 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600143 ER PT J AU DIMITROV, D LITTMAN, D MANISCHEWITZ, J BLUMENTHAL, R GOLDING, H AF DIMITROV, D LITTMAN, D MANISCHEWITZ, J BLUMENTHAL, R GOLDING, H TI KINETICS OF CELL-FUSION, MEDIATED BY THE HIV-1 ENVELOPE GLYCOPROTEIN INTERACTION WITH A HYBRID CD4.CD8 MOLECULE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S72 EP S72 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600196 ER PT J AU DITTMER, J GITLIN, SD REID, RL BRADY, JN AF DITTMER, J GITLIN, SD REID, RL BRADY, JN TI TRANSACTIVATION OF THE P2 PROMOTER OF THE PARATHYROID-HORMONE RELATED PROTEIN (PTHRP) BY HTLV-I TAX(1) - EVIDENCE FOR THE INVOLVEMENT OF PROTOONCOGENE PRODUCT ETSL SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S117 EP S117 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600352 ER PT J AU DUNBAR, CE BODINE, DM SORRENTINO, B DONAHUE, R MCDONAGH, K KARLSSON, S NIENHUIS, AW AF DUNBAR, CE BODINE, DM SORRENTINO, B DONAHUE, R MCDONAGH, K KARLSSON, S NIENHUIS, AW TI GENE-TRANSFER INTO HEMATOPOIETIC STEM-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S20 EP S20 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600012 ER PT J AU ENSOLI, B BARILLARI, G ALBINI, A FIORELLI, V MARKHAM, P GENDELMAN, R GALLO, RC AF ENSOLI, B BARILLARI, G ALBINI, A FIORELLI, V MARKHAM, P GENDELMAN, R GALLO, RC TI COOPERATION OF HIV-1 TAT PROTEIN, INFLAMMATORY CYTOKINES AND BASIC FIBROBLAST GROWTH-FACTOR (BFGF) IN THE PATHOGENESIS OF AIDS-KAPOSIS SARCOMA (AIDS-KS) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NATL CANC INST,I-16132 GENOA,ITALY. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S53 EP S53 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600129 ER PT J AU ENSOLI, B MARKHAM, P KAO, V RAFFELD, M GENDELMAN, R BARILLARI, G ZON, G GALLO, RC AF ENSOLI, B MARKHAM, P KAO, V RAFFELD, M GENDELMAN, R BARILLARI, G ZON, G GALLO, RC TI BASIC FIBROBLAST GROWTH-FACTOR (BFGF) INDUCES LESIONS IN MICE RESEMBLING KAPOSIS-SARCOMA (KS) AND ANTISENSE OLIGONUCLEOTIDES AGAINST THIS CYTOKINE INHIBIT THE GROWTH AND ANGIOGENIC ACTIVITY OF KS SPINDLE CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. LYNX THERAPEUT INC,FOSTER CITY,CA 94404. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S51 EP S51 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600119 ER PT J AU ENSOLI, F ENSOLI, B CAFARO, A VANELLI, GB GALLO, C PIZZO, PA THIELE, CJ AF ENSOLI, F ENSOLI, B CAFARO, A VANELLI, GB GALLO, C PIZZO, PA THIELE, CJ TI PRODUCTIVE HIV-1 INFECTION OF PRIMARY HUMAN NEUROBLASTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HENRY M JACKSON FDN,ROCKVILLE,MD. UNIV FLORENCE,DEPT ANAT & HISTOL,FLORENCE,ITALY. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,LTCB,BETHESDA,MD. RI Ensoli, Barbara/J-9169-2016; Cafaro, Aurelio/K-5314-2016 OI Ensoli, Barbara/0000-0002-0545-8737; NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S79 EP S79 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600222 ER PT J AU FAST, P KETTER, N WALKER, MC WESCOTT, SL SCHULTZ, AM AF FAST, P KETTER, N WALKER, MC WESCOTT, SL SCHULTZ, AM TI PHASE I/II TRIALS OF CANDIDATE HIV-1 VACCINES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,DIV AIDS,AIDS VACCINE CLIN TRIALS NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S49 EP S49 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600111 ER PT J AU FAUCI, AS AF FAUCI, AS TI IMMUNOPATHOGENIC MECHANISMS OF HIV-INFECTION - AN UPDATE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S77 EP S77 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600214 ER PT J AU FELBER, BK SONG, S CONSTANTOULAKIS, P SCHNEIDER, R NASIOULAS, G CUNNINGHAM, CP PAVLAKIS, GN AF FELBER, BK SONG, S CONSTANTOULAKIS, P SCHNEIDER, R NASIOULAS, G CUNNINGHAM, CP PAVLAKIS, GN TI NEW GENE-TRANSFER VECTORS FOR THE INHIBITION OF HIV-1 EXPRESSION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S20 EP S20 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600013 ER PT J AU FIORELLI, V GALLO, RC ENSOLI, B AF FIORELLI, V GALLO, RC ENSOLI, B TI THE EFFECT OF HIV-1 TAT PROTEIN ON THE CELL-CYCLE OF CYTOKINE-ACTIVATED ENDOTHELIAL-CELLS RESEMBLES THAT OF BASIC FIBROBLAST GROWTH-FACTOR (BFGF) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S53 EP S53 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600128 ER PT J AU FOLI, A SAVILLE, MW YARCHOAN, R AF FOLI, A SAVILLE, MW YARCHOAN, R TI MECHANISMS FOR THE OVERPRODUCTION OF INTERLEUKIN-6 (IL-6) AND TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN HIV-INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S75 EP S75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600209 ER PT J AU FOX, LM POLI, G STANLEY, SK FAUCI, AS AF FOX, LM POLI, G STANLEY, SK FAUCI, AS TI PENTOXIFYLLINE CAN INHIBIT HIV THROUGH MECHANISMS INDEPENDENT OF INHIBITION OF TNFA SECRETION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,LIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S28 EP S28 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600040 ER PT J AU FRANCHINI, G MULLOY, J KORALNIK, I BOERI, E LOMONICO, A SCHLEGEL, R LEONARD, W GALLO, RC AF FRANCHINI, G MULLOY, J KORALNIK, I BOERI, E LOMONICO, A SCHLEGEL, R LEONARD, W GALLO, RC TI BIOLOGICAL FEATURES OF THE HTLV-I P12(I) PROTEIN AND ITS POSSIBLE ROLE IN HTLV-I PATHOGENESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIHLB,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD. GEORGETOWN UNIV,WASHINGTON,DC. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S114 EP S114 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600342 ER PT J AU FRANCHINI, G MULLOY, J KORALNIK, I BOERI, E LOMONICO, A SCHLEGEL, R LEONARD, W GALLO, RC AF FRANCHINI, G MULLOY, J KORALNIK, I BOERI, E LOMONICO, A SCHLEGEL, R LEONARD, W GALLO, RC TI BIOLOGICAL FEATURES OF THE HTLV-I P12(I) PROTEIN AND ITS POSSIBLE ROLE IN HTLV-I PATHOGENESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIHLB,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD. GEORGETOWN UNIV,WASHINGTON,DC. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S114 EP S114 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600341 ER PT J AU FRANCHINI, G GUROFF, M TARTAGLIA, J AGGARAWAL, A ABIMIKU, A MARKHAM, P LIMBACH, K SADOFF, HJ PAOLETTI, E GALLO, RC AF FRANCHINI, G GUROFF, M TARTAGLIA, J AGGARAWAL, A ABIMIKU, A MARKHAM, P LIMBACH, K SADOFF, HJ PAOLETTI, E GALLO, RC TI PRIME/BOOST PROTOCOLS UTILIZING HIGHLY ATTENUATED POXVIRUS VECTORS CONFER PROTECTION AGAINST HIV-2 CHALLENGE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. VIROGENET CORP,TROY,NY 12180. ADV BIOSCI LABS,KENSINGTON,MD. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S43 EP S43 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600089 ER PT J AU FRANZOSO, G BOURS, V AZARENKO, V PARK, S TOMITAYAMAGUCHI, M SIEBENLIST, U AF FRANZOSO, G BOURS, V AZARENKO, V PARK, S TOMITAYAMAGUCHI, M SIEBENLIST, U TI AN INDIRECT ROLE FOR BCL-3 IN NF-KAPPA-B-MEDIATED TRANSACTIVATION AFTER CELLULAR-STIMULATION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S96 EP S96 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600280 ER PT J AU GALLO, RC KLOTMAN, ME AF GALLO, RC KLOTMAN, ME TI ABSTRACTS AND SELECTED PAPERS FROM THE 1993 ANNUAL-MEETING OF THE LABORATORY OF TUMOR-CELL BIOLOGY - AUGUST 22-28, 1993, BETHESDA, MARYLAND - INTRODUCTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material RP GALLO, RC (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A11,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S1 EP S1 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600001 ER PT J AU GAO, F YUE, L BIGGAR, RJ NEEQUAYE, AE HO, DD SHARP, PM SHAW, GM HAHN, BH AF GAO, F YUE, L BIGGAR, RJ NEEQUAYE, AE HO, DD SHARP, PM SHAW, GM HAHN, BH TI GENETIC AND BIOLOGICAL VARIATION OF HIV-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. UNIV GHANA,DEPT MED,ACCRA,GHANA. AARON DIAMOND AIDS RES CTR,NEW YORK,NY. UNIV DUBLIN TRINITY COLL,DEPT GENET,DUBLIN 2,IRELAND. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S107 EP S107 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600318 ER PT J AU GAO, WY SHIRASAKA, T JOHNS, DG BRODER, S MITSUYA, H AF GAO, WY SHIRASAKA, T JOHNS, DG BRODER, S MITSUYA, H TI DISPROPORTIONATE ANTI-HIV-1 ACTIVITY OF DIDEOXYNUCLEOSIDE ANALOGS IN RESTING AND ACTIVATED HUMAN-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S25 EP S25 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600029 ER PT J AU GARRITY, R RIMMELZWAAN, G MINASSIAN, A TSAI, WP CONLEY, S DUNLOP, N DEJONG, J KEULEN, W GOUDSMIT, J NARA, P AF GARRITY, R RIMMELZWAAN, G MINASSIAN, A TSAI, WP CONLEY, S DUNLOP, N DEJONG, J KEULEN, W GOUDSMIT, J NARA, P TI INTRODUCTION OF POTENTIAL N-LINKED GLYCOSYLATION SITES INTO V3 DOMAIN OF HIV-1 GP120 - EFFECTS ON VIRUS VIABILITY ANTIGENICITY AND IMMUNOGENICITY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIV AMSTERDAM,ACAD MED CTR,1105 AZ AMSTERDAM,NETHERLANDS. NCI,FCDRF,LTCB,BETHESDA,MD. NCI,FCDRF,PRI DYNCORP,BCDP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S37 EP S37 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600072 ER PT J AU GARZINODEMO, A JOLICOEUR, P HANNA, Z GALLO, RC LUSSO, P AF GARZINODEMO, A JOLICOEUR, P HANNA, Z GALLO, RC LUSSO, P TI TRANSACTIVATION OF CD4 PROMOTERS BY HUMAN HERPESVIRUS-6 (HHV-6) INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, TUMOR CELL BIOL LAB, BETHESDA, MD 20892 USA. CLIN RES INST MONTREAL, MONTREAL H2W 1R7, PQ, CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S123 EP S123 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600375 ER PT J AU GARZINODEMO, A GALLO, RC ARYA, SK AF GARZINODEMO, A GALLO, RC ARYA, SK TI TOWARDS DEVELOPING HIV-2 BASED RETROVIRAL VECTORS FOR GENE-THERAPY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S22 EP S22 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600018 ER PT J AU GITLIN, SD DITTMER, J SHIN, RC BRADY, JN AF GITLIN, SD DITTMER, J SHIN, RC BRADY, JN TI TRANSCRIPTIONAL ACTIVATION OF THE HTLV-I LTR BY FUNCTIONAL INTERACTION OF TAX, AND ETS1 WITH CELLULAR TRANSCRIPTION FACTORS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S116 EP S116 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600350 ER PT J AU GIUSTI, RM GRACIA, F STEPHENS, K FUKUDA, K VITEK, C HARTGE, P LEVIN, A BLATTNER, W LEVINE, P KAPLAN, J AF GIUSTI, RM GRACIA, F STEPHENS, K FUKUDA, K VITEK, C HARTGE, P LEVIN, A BLATTNER, W LEVINE, P KAPLAN, J TI A SEARCH FOR DISEASES ASSOCIATED WITH HTLV-II AMONG GUAYMI PATIENTS, PANAMA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. GORGAS MEM LAB,PANAMA CITY,PANAMA. CDC,RETROVIRUS DIS BRANCH,ATLANTA,GA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S112 EP S112 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600336 ER PT J AU GONDA, MA PALLANSCH, LA OBERSTE, MS CENTANNI, JM GREENWOOD, JD WILLIAMSON, JC AF GONDA, MA PALLANSCH, LA OBERSTE, MS CENTANNI, JM GREENWOOD, JD WILLIAMSON, JC TI PATHOGENESIS OF VIRAL GENE-EXPRESSION IN BOVINE IMMUNODEFICIENCY VIRUS (BIV) TRANSGENIC MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S87 EP S87 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600253 ER PT J AU GORELICK, RJ CHABOT, DJ HENDERSON, LE ARTHUR, LO AF GORELICK, RJ CHABOT, DJ HENDERSON, LE ARTHUR, LO TI MUTAGENESIS STUDIES OF THE CONSERVED PTAPP SEQUENCE IN THE P6 PROTEIN OF HIV-1 - EFFECTS ON FULL-LENGTH GENOMIC RNA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NR 3 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S97 EP S97 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600284 ER PT J AU GURGO, C LUSSO, P CROWLEY, R REITZ, MS GALLO, RC AF GURGO, C LUSSO, P CROWLEY, R REITZ, MS GALLO, RC TI DYNAMICS OF EXPRESSION OF CD4 AND VIRUS PRODUCTION IN CLONES OF JURKAT CELLS OBTAINED FROM AN HIV-1 TRANSFECTED LINE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. CEOS,NAPLES,ITALY. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S83 EP S83 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600239 ER PT J AU HAVERKOS, HW DROTMAN, DP HANSON, D AF HAVERKOS, HW DROTMAN, DP HANSON, D TI EPIDEMIOLOGY OF AIDS-RELATED KAPOSIS-SARCOMA (KS) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 CTR DIS CONTROL,ATLANTA,GA. NIDA,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S55 EP S55 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600136 ER PT J AU HENDERSON, LE SOWDER, RC BESS, JW CASASFINET, JR YU, X FENSELAU, C RICE, WG MENDELEYEV, J WINK, DA KUN, E ARTHUR, LO AF HENDERSON, LE SOWDER, RC BESS, JW CASASFINET, JR YU, X FENSELAU, C RICE, WG MENDELEYEV, J WINK, DA KUN, E ARTHUR, LO TI HIV-1 ZINC FINGERS - A TARGET FOR RATIONAL DRUG DEVELOPMENT SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702. UNIV MARYLAND,DEPT BIOCHEM & CHEM,BALTIMORE,MD 21228. OCTAMER INC,ENVIRONM BIOCHEM LAB,TIBURON,CA 94920. NCI,DCE,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S27 EP S27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600039 ER PT J AU HOFF, R LAWRENCE, DN FISCHER, R VERMUND, S BARKER, L AF HOFF, R LAWRENCE, DN FISCHER, R VERMUND, S BARKER, L TI PRIMARY AND SECONDARY END-POINTS FOR HIV VACCINE EFFICACY TRIALS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,DIV AIDS,TRP,VACCINE TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S49 EP S49 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600113 ER PT J AU HOLMES, AM BARILLARI, G GALLO, RC ENSOLI, B AF HOLMES, AM BARILLARI, G GALLO, RC ENSOLI, B TI INTEGRIN-MEDIATED UPTAKE OF HIV-1 TAT PROTEIN BY CYTOKINE-ACTIVATED ENDOTHELIAL-CELLS (EC) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S53 EP S53 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600130 ER PT J AU HOPE, TJ HUNTER, J MANCUSO, VA DERSE, D PHILLIPS, T PARSLOW, TG AF HOPE, TJ HUNTER, J MANCUSO, VA DERSE, D PHILLIPS, T PARSLOW, TG TI POSTTRANSCRIPTIONAL REGULATORY DOMAINS FROM RETROVIRAL REV AND REX PROTEINS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 SCRIPPS CLIN & RES FDN,DEPT NEUROPHARMACOL,LA JOLLA,CA 92037. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S94 EP S94 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600274 ER PT J AU JACOBSON, S ELOVAARA, I LEHKY, T WALTER, M FOX, C AF JACOBSON, S ELOVAARA, I LEHKY, T WALTER, M FOX, C TI IMMUNOPATHOGENIC ROLE OF HTLV-I SPECIFIC CYTOTOXIC T-CELL RESPONSES IN PATIENTS WITH HTLV-I-ASSOCIATED NEUROLOGIC DISEASE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S115 EP S115 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600346 ER PT J AU JOHNSON, RP KALAMS, S BLATTNER, W WALKER, BD AF JOHNSON, RP KALAMS, S BLATTNER, W WALKER, BD TI HIV SEQUENCE VARIATION AS A MECHANISM OF ESCAPE FROM CYTOTOXIC T-LYMPHOCYTES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02129. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S39 EP S39 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600077 ER PT J AU JORDAN, EK FRANK, JA GRIMLEY, P SNOY, PJ HEYES, MP STONE, G POSSE, S LEBIHAN, D CUENOD, C TORNATORE, G AF JORDAN, EK FRANK, JA GRIMLEY, P SNOY, PJ HEYES, MP STONE, G POSSE, S LEBIHAN, D CUENOD, C TORNATORE, G TI NEUROLOGICAL AIDS IN THE RHESUS-MONKEY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NINCDS,AHCS,BETHESDA,MD. US FDA,DOQC,CBER,ROCKVILLE,MD. NIMH,LCS,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIH,OD,LDR,BETHESDA,MD. NINCDS,LCNSS,BETHESDA,MD. NIH,BEIP,BETHESDA,MD. NIH,CC,DR,BETHESDA,MD. NINCDS,LVMP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S80 EP S80 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600227 ER PT J AU KASHANCHI, F THOMPSON, J SADAIE, R BRADY, J DONIGER, J ROSENTHAL, LJ AF KASHANCHI, F THOMPSON, J SADAIE, R BRADY, J DONIGER, J ROSENTHAL, LJ TI THE ORF-1 GENE WITHIN HHV-6 SALI-L UP-REGULATES HIV-1 EXPRESSION AND REACTIVATES HIV-1 LATENT INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20007. NIDR,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S124 EP S124 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600376 ER PT J AU KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A BRADY, JN AF KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A BRADY, JN TI DIRECT INTERACTION OF THE HIV-1 TRANSACTIVATOR TAT WITH HUMAN TFIID SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S95 EP S95 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600276 ER PT J AU KINDT, TJ HAGUE, BF CHO, SG ZHAO, TM SIMPSON, RM AF KINDT, TJ HAGUE, BF CHO, SG ZHAO, TM SIMPSON, RM TI RABBIT INFECTION WITH HIV-1 - MAKING IT BETTER SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S89 EP S89 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600260 ER PT J AU KINTER, AL POLI, G FAUCI, AS AF KINTER, AL POLI, G FAUCI, AS TI ENDOGENOUS CYTOKINES DRIVE HIV-1 REPLICATION IN PRIMARY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS (PBMC) STIMULATED WITH IL-2 IN THE ABSENCE OF MITOGENS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S76 EP S76 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600210 ER PT J AU KLOTMAN, ME LI, G THOMSON, M ROSS, M NELSON, P ZON, G WHITTAKER, P GALLO, RC AF KLOTMAN, ME LI, G THOMSON, M ROSS, M NELSON, P ZON, G WHITTAKER, P GALLO, RC TI EVALUATION OF MOLECULAR APPROACHES TO INHIBITING REV/RRE INTERACTIONS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LYNX THERAPEUT,FOSTER CITY,CA. RI klotman, mary/A-1921-2016 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S30 EP S30 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600049 ER PT J AU KLOTMAN, P KOPP, J OWENS, J RAY, P BROWNING, P ADLER, S RICHARDSON, M BRYANT, J BRUGGEMAN, L RAPPAPORT, J NOTKINS, A AF KLOTMAN, P KOPP, J OWENS, J RAY, P BROWNING, P ADLER, S RICHARDSON, M BRYANT, J BRUGGEMAN, L RAPPAPORT, J NOTKINS, A TI TRANSGENIC MICE AS MODELS FOR HIV PATHOGENESIS AND THERAPY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIH,LDB,BETHESDA,MD. NIH,LOM,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S87 EP S87 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600251 ER PT J AU KOJIMA, E SHIRASAKA, T ANDERSON, B CHOKEKIJCHAI, S YARCHOAN, R MITSUYA, H AF KOJIMA, E SHIRASAKA, T ANDERSON, B CHOKEKIJCHAI, S YARCHOAN, R MITSUYA, H TI ANTI-HIV THERAPY AND MONITORING ITS EFFECT USING POLYMERASE CHAIN-REACTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S79 EP S79 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600221 ER PT J AU KOLESNITCHENKO, V TIAN, H HARTMANN, D DONOGHUE, E MCGOWAN, C COSSMAN, J RUSSELL, P SAMELSON, L SHAW, G COHEN, DI AF KOLESNITCHENKO, V TIAN, H HARTMANN, D DONOGHUE, E MCGOWAN, C COSSMAN, J RUSSELL, P SAMELSON, L SHAW, G COHEN, DI TI ABNORMAL-CELL CYCLE EVENTS TRIGGERED IN HIV-MEDIATED T-CELL KILLING SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, SCH MED, DEPT PATHOL, WASHINGTON, DC 20007 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. UNIV ALABAMA, BIRMINGHAM, AL 35294 USA. NICHHD, CBMB, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S62 EP S62 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600158 ER PT J AU KRONER, BL CARRINGTON, M GOEDERT, JJ MANN, DL AF KRONER, BL CARRINGTON, M GOEDERT, JJ MANN, DL TI CONCORDANCE OF HLA HAPLOTYPE SHARING AND AIDS/CD4 DECLINE IN HEMOPHILIC SIBLING PAIRS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,PRI DYNCORP,RTI,ROCKVILLE,MD. NCI,PRI DYNCORP,RTI,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S107 EP S107 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600321 ER PT J AU LAGRENADE, L PATE, E RODGERSJOHNSON, P HANCHARD, B CRANSTON, B JOHNSON, BK VENKATESHAN, CN GIBBS, CJ BLATTNER, W AF LAGRENADE, L PATE, E RODGERSJOHNSON, P HANCHARD, B CRANSTON, B JOHNSON, BK VENKATESHAN, CN GIBBS, CJ BLATTNER, W TI HTLV-1, FAMILIAL OCCURRENCE OF INFECTIVE DERMATITIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NCI,ENVIRONM EPIDEMIOL BRANCH,VIRAL EPIDEMIOL SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S112 EP S112 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600337 ER PT J AU LEE, SG KALYAN, NK WILHELM, J PISANO, MR HUM, WT ROBERTGUROFF, M HUNG, PP AF LEE, SG KALYAN, NK WILHELM, J PISANO, MR HUM, WT ROBERTGUROFF, M HUNG, PP TI GENERATION OF CUSTOM-DESIGNED MONO-SPECIFIC ANTIBODIES BY USE OF AN IMMUNOGENIC PROTEIN CARRIER SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 WYETH AYERST RES,DIV BIOTECH & MICRO,PHILADELPHIA,PA 19101. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S47 EP S47 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600105 ER PT J AU LEMPICKI, RA TANI, Y GEIGER, S ZOLLAPAZNER, S LANE, HC COHEN, DI AF LEMPICKI, RA TANI, Y GEIGER, S ZOLLAPAZNER, S LANE, HC COHEN, DI TI EVALUATION OF T-LYMPHOCYTES EXPRESSING GENETICALLY-ENGINEERED HIV-ENV SPECIFIC RECEPTORS AS AN EFFECTIVE THERAPY FOR HIV-1 INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S34 EP S34 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600061 ER PT J AU LEVINE, PH WHIDESIDE, T HERBERMAN, RB AF LEVINE, PH WHIDESIDE, T HERBERMAN, RB TI LOW NATURAL-KILLER-CELL ACTIVITY AND ITS POSSIBLE RELATIONSHIP TO CHRONIC FATIGUE SYNDROME AND CANCER SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. PITTSBURGH CANC INST,PITTSBURGH,PA 15213. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S125 EP S125 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600381 ER PT J AU LEVINE, PH STEMMERMAN, G LENETTE, E HILDESHEIM, A AF LEVINE, PH STEMMERMAN, G LENETTE, E HILDESHEIM, A TI PATTERNS OF EPSTEIN-BARR-VIRUS ANTIBODY PRIOR TO THE DIAGNOSIS OF EBV-ASSOCIATED GASTRIC-CARCINOMA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. HONOLULU HEART PROGRAM,HONOLULU,HI. VIROLABS,SAN FRANCISCO,CA. NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S125 EP S125 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600382 ER PT J AU LEVINE, PH AF LEVINE, PH TI AN EPSTEIN-BARR-VIRUS VACCINE TO PREVENT CANCER - PROS AND CONS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S125 EP S125 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600380 ER PT J AU LI, G THOMSON, MM ZON, G WHITTAKER, P GALLO, RC KLOTMAN, ME AF LI, G THOMSON, MM ZON, G WHITTAKER, P GALLO, RC KLOTMAN, ME TI SIMULTANEOUS TREATMENT OF HIV-1-INFECTED CELLS WITH ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE ANALOGS (S-ODN) DIRECTED AGAINST MULTIPLE TARGETS IN THE HIV-1 GENOME HAVE ADDITIVE ANTIVIRAL EFFECTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LYNX THERAPEUT,FOSTER CITY,CA 94404. RI klotman, mary/A-1921-2016 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S31 EP S31 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600051 ER PT J AU LINDHOLM, PF REID, RL KASHANCHI, F BRADY, JN AF LINDHOLM, PF REID, RL KASHANCHI, F BRADY, JN TI HTLV-1 TAX(1) PROTEIN PHYSICALLY INTERACTS WITH PROTEIN-KINASE-C IN-VITRO SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S116 EP S116 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600351 ER PT J AU LISZIEWICZ, J SUN, D SMYTHE, J LUSSO, P LORI, F ENSOLI, B CHANG, HK PENG, B TRAPNELL, B WEICHOLD, F KLOTMAN, M AGRAWAL, S REITZ, M GALLO, RC AF LISZIEWICZ, J SUN, D SMYTHE, J LUSSO, P LORI, F ENSOLI, B CHANG, HK PENG, B TRAPNELL, B WEICHOLD, F KLOTMAN, M AGRAWAL, S REITZ, M GALLO, RC TI MOLECULAR APPROACHES FOR THE TREATMENT OF HIV-1 INFECTION - GENE-THERAPY AND ANTISENSE THERAPY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. JOHNSON & JOHNSON RES PTY LTD SYDNEY,RUS,NSW 2010,AUSTRALIA. GENET THERAPY INC,GAITHERSBURG,MD. HYBRIDON INC,WORCESTER,MA 01605. RI klotman, mary/A-1921-2016; Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S19 EP S19 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600007 ER PT J AU LORI, F GAO, WY CARA, A GALLO, RC AF LORI, F GAO, WY CARA, A GALLO, RC TI MECHANISM OF HIV-1 REPLICATION AND LATENCY IN QUIESCENT LYMPHOCYTES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S94 EP S94 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600272 ER PT J AU LUCEY, D GARTNER, S AF LUCEY, D GARTNER, S TI GOES THE SUBSTANCE-P RECEPTOR CONTRIBUTE TO THE FUSION PROCESS OF RETROVIRUSES AND TO THE PATHOGENESIS OF HIV/AIDS - AN HYPOTHESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. HENRY M JACKSON FDN,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S74 EP S74 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600205 ER PT J AU LUNARDIISKANDAR, Y BRYANT, J LAM, VH ZEMAN, RA GESSAIN, A VARRICCHIO, F GALLO, RC AF LUNARDIISKANDAR, Y BRYANT, J LAM, VH ZEMAN, RA GESSAIN, A VARRICCHIO, F GALLO, RC TI A MODEL OF TROPICAL SPASTIC PARAPARESIS HTLV-I-ASSOCIATED MYELOPATHY (TSP/HAM) DISEASE IN IMMUNODEFICIENT MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. INST PASTEUR,PARIS,FRANCE. US FDA,CBER,ROCKVILLE,MD. NR 1 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S120 EP S120 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600362 ER PT J AU LUNARDIISKANDAR, Y LAM, V GILL, P ZEMAN, RA MICHAELS, F REITZ, MS BERNEMAN, ZA BRYANT, J GALLO, RC AF LUNARDIISKANDAR, Y LAM, V GILL, P ZEMAN, RA MICHAELS, F REITZ, MS BERNEMAN, ZA BRYANT, J GALLO, RC TI THE FIRST KAPOSIS-SARCOMA (KS)-DERIVED CELL-LINE (KSY-1) - RELATED TO AND DIFFERENCES FROM KS CELL STRAINS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES,CA 90033. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S52 EP S52 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600124 ER PT J AU LUSSO, P SECCHIERO, P CROWLEY, RW GARZINODEMO, A BERNEMAN, ZN GALLO, RC AF LUSSO, P SECCHIERO, P CROWLEY, RW GARZINODEMO, A BERNEMAN, ZN GALLO, RC TI HUMAN HERPESVIRUS-7 (HHV-7) USES CD4 AS A RECEPTOR AND INTERFERES WITH HIV-INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S24 EP S24 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600026 ER PT J AU MALYKH, A LORI, F HALL, L GALLO, RC REITZ, MS AF MALYKH, A LORI, F HALL, L GALLO, RC REITZ, MS TI THE V3 LOOP OF HIV-1 IS NOT SUFFICIENT FOR GROWTH IN MONOCYTE-MACROPHAGES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S42 EP S42 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600087 ER PT J AU MANN, DL ODONNELL, M HARDING, A MARDI, D CARRINGTON, M GOEDERT, JJ AF MANN, DL ODONNELL, M HARDING, A MARDI, D CARRINGTON, M GOEDERT, JJ TI A ROLE FOR THE MAJOR HISTOCOMPATABILITY COMPLEX IN HIV-1 PATHOGENESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,VIRAL CARCINOGENESIS BRANCH,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,VIRAL EPIDEMIOL BRANCH,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S71 EP S71 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600191 ER PT J AU MARSH, J RHEE, S DE, S AF MARSH, J RHEE, S DE, S TI HIV-1 NEF ACTIVITY IS NEITHER SPECIES-RESTRICTED NOR LIMITED TO T-CELL FUNCTIONS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S93 EP S93 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600271 ER PT J AU MERGES, MJ LAYNE, SP SPOUGE, JL NARA, PL AF MERGES, MJ LAYNE, SP SPOUGE, JL NARA, PL TI HIV-1 V3-SPECIFIC NEUTRALIZATION - VALENCY, REVERSIBILITY, AND THE STATE OF THE VIRION DETERMINE IN-VITRO EFFICACY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FCRDC,LTCB,VBU,FREDERICK,MD. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NIH,NATL LIB MED,NCBI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S42 EP S42 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600088 ER PT J AU MORGAN, RA RAGHEB, J CHUAHVANDENDENDRIESSCHE, M VANDENDENDRIESSCHE, T DETTENHOFER, M BRESSLER, P AF MORGAN, RA RAGHEB, J CHUAHVANDENDENDRIESSCHE, M VANDENDENDRIESSCHE, T DETTENHOFER, M BRESSLER, P TI PROGRESS TOWARDS GENE-THERAPY FOR AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S21 EP S21 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600015 ER PT J AU MORTON, WR SCHMIDT, AM AGY, MB KATZE, MG FLOREY, MJ COREY, L FRUMKIN, LR OCHS, HD HU, SL MCCLURE, J BENVENISTE, RE AF MORTON, WR SCHMIDT, AM AGY, MB KATZE, MG FLOREY, MJ COREY, L FRUMKIN, LR OCHS, HD HU, SL MCCLURE, J BENVENISTE, RE TI INFECTION OF MACACA-NEMESTRINA BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. BRISTOL MYERS SQUIBB CO,SEATTLE,WA. UNIV WASHINGTON,PRIMATE RES CTR,SEATTLE,WA. UNIV WASHINGTON,DEPT LAB MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT PEDIAT,SEATTLE,WA 98195. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S86 EP S86 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600247 ER PT J AU MULLOY, JC BOERI, E KORALNIK, IJ GALLO, RC LEONARD, W FRANCHINI, G AF MULLOY, JC BOERI, E KORALNIK, IJ GALLO, RC LEONARD, W FRANCHINI, G TI THE HTLV-I P12(I) PROTEIN, SIMILAR TO P56(LCK), PHYSICALLY BINDS TO THE ACIDIC REGION OF THE BETA-CHAIN OF THE INTERLEUKIN-2 RECEPTOR (IL-2R) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NHLBI,PULMONARY & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S117 EP S117 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600354 ER PT J AU MURPHEYCORB, M OHKAWA, S WILSON, LA DETRICH, B VOGEL, F SCHULTZ, A AF MURPHEYCORB, M OHKAWA, S WILSON, LA DETRICH, B VOGEL, F SCHULTZ, A TI COMPARATIVE EFFICACY OF WHOLE KILLED SIV VACCINES WITH VARIOUS ADJUVANTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,DIV AIDS,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,WASHINGTON,DC. TULANE PRIMATE CTR,COVINGTON,LA. NR 0 TC 1 Z9 1 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 AUG PY 1994 VL 10 SU 1 BP S86 EP S86 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600246 ER PT J AU NARA, PL MERGES, M MUSSON, S CONLEY, S HOGERVORST, E GOUDSMIT, J HENDERSON, L ARTHUR, L DUNLOP, N AF NARA, PL MERGES, M MUSSON, S CONLEY, S HOGERVORST, E GOUDSMIT, J HENDERSON, L ARTHUR, L DUNLOP, N TI HUMAN PLASMA-PROTEINS AND HIV-1 - A MISSING LINK IN OUR UNDERSTANDING OF THE PATHOBIOLOGY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,LTCB,VBU,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BCDP,FREDERICK,MD 21702. UNIV AMSTERDAM,ACAD MED CTR,1105 AZ AMSTERDAM,NETHERLANDS. NR 0 TC 2 Z9 2 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 AUG PY 1994 VL 10 SU 1 BP S71 EP S71 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600193 ER PT J AU NEUMANN, M KLEINSCHMIDT, A ERFLE, V FELBER, BK PAVLAKIS, G BRACKWERNER, R AF NEUMANN, M KLEINSCHMIDT, A ERFLE, V FELBER, BK PAVLAKIS, G BRACKWERNER, R TI INTRACELLULAR RESTRICTION OF HIV-1 PRODUCTION IN HUMAN ASTROCYTES IS ASSOCIATED WITH IMPAIRED REV FUNCTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. GSF MUNICH,INST MOLEC VIROL,W-8042 NEUHERBERG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S98 EP S98 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600291 ER PT J AU NIGIDA, SM SMITH, CH SHOEMAKER, MR ARTHUR, LO AF NIGIDA, SM SMITH, CH SHOEMAKER, MR ARTHUR, LO TI CLONED HIV-1(MN)-EXPRESSING CELL-LINES - SELECTION OF SPECIFIC VIRUS GENOTYPES AND PHENOTYPES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE DEV PROGRAM,VIRAL DIS & IMMUN SECT,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S83 EP S83 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600240 ER PT J AU NOGUCHI, M YI, HF ROSENBLATT, HM FILIPOVICH, AH ADELSTEIN, S MODI, WS MCBRIDE, OW LEONARD, WJ AF NOGUCHI, M YI, HF ROSENBLATT, HM FILIPOVICH, AH ADELSTEIN, S MODI, WS MCBRIDE, OW LEONARD, WJ TI INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN (IL-2R-GAMMA) MUTATION RESULTS IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY (XSCID) IN HUMANS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD. NCI,BIOCHEM LAB,BETHESDA,MD. BAYLOR COLL MED,HOUSTON,TX. NCI,FCRDC,PRI DYNCORP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S102 EP S102 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600302 ER PT J AU NORCROSS, MA RODERIQUEZ, G YANAGISHITA, M BOUHABIB, D PATEL, M ORAVECZ, T AF NORCROSS, MA RODERIQUEZ, G YANAGISHITA, M BOUHABIB, D PATEL, M ORAVECZ, T TI CELL-SURFACE HEPARAN-SULFATE INTERACTS WITH THE V3 REGION ON GP120/41 OLIGOMERS TO MEDIATE HIV-1 BINDING AND INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20014. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S75 EP S75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600206 ER PT J AU OBRIEN, JR DIAMONDSTONE, L GOEDERT, J AF OBRIEN, JR DIAMONDSTONE, L GOEDERT, J TI IDIOPATHIC CD4+ T-LYMPHOCYTOPENIA (ICL) AMONG HIV-1 SERONEGATIVE HEMOPHILIACS AND FEMALE PARTNERS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S80 EP S80 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600226 ER PT J AU OBRIEN, SJ DEAN, M WINKLER, C STEPHENS, JC MANN, D GOEDERT, J GOMPERTS, E KASLOW, R BUCKBINDER, S AF OBRIEN, SJ DEAN, M WINKLER, C STEPHENS, JC MANN, D GOEDERT, J GOMPERTS, E KASLOW, R BUCKBINDER, S TI AIDS AND THE HUMAN GENOME PROJECT SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 SAN FRANCISCO CITY CLIN,SAN FRANCISCO,CA. NIAID,BETHESDA,MD 20892. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. NCI,BETHESDA,MD 20892. PRI DYNCORP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S82 EP S82 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600236 ER PT J AU OPPENHEIM, JJ LLOYD, A TAUB, D WANG, JM KELVIN, D AF OPPENHEIM, JJ LLOYD, A TAUB, D WANG, JM KELVIN, D TI CONTRIBUTION OF RECEPTORS AND ADHESION MOLECULES TO CHEMOKINE ACTIVITIES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BRMP,LMI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP INC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S102 EP S102 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600303 ER PT J AU OTT, DE SOWDER, RC NIGIDA, SM GORELICK, RJ HENDERSON, LE ARTHUR, LO AF OTT, DE SOWDER, RC NIGIDA, SM GORELICK, RJ HENDERSON, LE ARTHUR, LO TI A CONSERVED GAG PROTEIN MOTIF IS DUPLICATED IN A NOVEL HIV-1(MN) PROVIRUS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S97 EP S97 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600285 ER PT J AU PAUL, WE AF PAUL, WE TI IL-4 - SIGNALING MECHANISMS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S101 EP S101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600299 ER PT J AU PINCUS, SH MESSER, KG AF PINCUS, SH MESSER, KG TI FINE SPECIFICITY ANALYSIS OF ANTIBODY-RESPONSE TO HIV ENVELOPE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S35 EP S35 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600065 ER PT J AU POLI, G WEISSMAN, D KINTER, AL FAUCI, AS AF POLI, G WEISSMAN, D KINTER, AL FAUCI, AS TI IL-10 AND THE TH-2 CYTOKINE IL-4 REGULATE HIV REPLICATION IN HUMAN MACROPHAGES IN CONCERT WITH PROINFLAMMATORY CYTOKINES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,LIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S71 EP S71 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600190 ER PT J AU POTTER, M JONES, G MULLER, J JANZ, S AF POTTER, M JONES, G MULLER, J JANZ, S TI CHROMOSOMAL TRANSLOCATION IS AN EARLY STEP IN MOUSE PLASMACYTOMAGENESIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,DIV CANC BIOL DIAG & CTR,GENET LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S59 EP S59 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600151 ER PT J AU RABKIN, CS WILSON, SE GOEDERT, JJ AF RABKIN, CS WILSON, SE GOEDERT, JJ TI CHANGES IN RISKS OF OPPORTUNISTIC INFECTIONS AND CANCER WITH CD4 LYMPHOPENIA IN THE THERAPY ERA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. ARC,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S108 EP S108 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600325 ER PT J AU RAPPAPORT, J BRUGGEMAN, L ADLER, S KLOTMAN, P AF RAPPAPORT, J BRUGGEMAN, L ADLER, S KLOTMAN, P TI POSITIVE AND NEGATIVE REGULATION OF HIV THROUGH VIRAL AND CELLULAR FACTORS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIDR,ORAL MED LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S95 EP S95 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600278 ER PT J AU RAUSCH, DM EIDEN, LE KALYANARAMAN, VS LIFSON, JD AF RAUSCH, DM EIDEN, LE KALYANARAMAN, VS LIFSON, JD TI CD4(81-92) PEPTIDES BLOCK INFECTION BY PEDIATRIC CLINICAL ISOLATES OF HIV-1 RESISTANT TO NEUTRALIZATION BY SCD4 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD. GENELABS INC,REDWOOD CITY,CA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S26 EP S26 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600034 ER PT J AU RAUSCH, DM EIDEN, LE AF RAUSCH, DM EIDEN, LE TI AZT TREATMENT DECREASES VIRUS IN SERUM AND CSF, AND DELAYS ONSET OF CNS IMPAIRMENTS IN INFANT RHESUS MACAQUES PERINATALLY INFECTED WITH SIVSMM/B670 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S25 EP S25 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600030 ER PT J AU RAY, PE BRUGGEMAN, LA WEEKS, BS KOPP, JB MESRI, EA NOTKINS, AL KLOTMAN, PE AF RAY, PE BRUGGEMAN, LA WEEKS, BS KOPP, JB MESRI, EA NOTKINS, AL KLOTMAN, PE TI ALTERATIONS IN EPIDERMAL GROWTH-FACTOR (EGF) AND BASIC FIBROBLAST GROWTH-FACTOR (BFGF) EXPRESSION IN HIV-1 TRANSGENIC MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 CHILDRENS NATL MED CTR,MD & CRI,WASHINGTON,DC 20010. NIDR,LBD & LOM,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S89 EP S89 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600261 ER PT J AU READCONNOLE, EL HALL, L REITZ, M POPOVIC, M AF READCONNOLE, EL HALL, L REITZ, M POPOVIC, M TI CELLULAR AND MOLECULAR CHARACTERIZATION OF 3 EARLY ISOLATES OF HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 ADV BIOSCI LAB,CELL BIOL SECT,KENSINGTON,MD 20893. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S92 EP S92 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600270 ER PT J AU REITZ, M VERONESE, FD LOUIE, A WATKINS, B GUPTA, G LUSSO, P GALLO, RC ROBERTGUROFF, M AF REITZ, M VERONESE, FD LOUIE, A WATKINS, B GUPTA, G LUSSO, P GALLO, RC ROBERTGUROFF, M TI CONFORMATIONAL ASPECTS OF V3 IN HIV-1 NEUTRALIZATION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87544. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S39 EP S39 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600076 ER PT J AU ROBERTGUROFF, M WATKINS, B STERN, TL ALDRICH, K KLASSE, PJ MCKEATING, J REITZ, MS GALLO, RC AF ROBERTGUROFF, M WATKINS, B STERN, TL ALDRICH, K KLASSE, PJ MCKEATING, J REITZ, MS GALLO, RC TI IMMUNOLOGICAL AND BIOLOGIC CONSEQUENCES OF HIV VARIABILITY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,LTCB,BETHESDA,MD 20892. CHESTER BEATTY LABS,LONDON,ENGLAND. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S39 EP S39 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600078 ER PT J AU ROSSIO, JL BESS, JW HENDERSON, LE ARTHUR, LO AF ROSSIO, JL BESS, JW HENDERSON, LE ARTHUR, LO TI MHC CLASS-II ANTIGEN ON HIV-1 IS FUNCTIONAL IN SUPERANTIGEN PRESENTATION TO HUMAN T-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S63 EP S63 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600164 ER PT J AU SADAIE, MR HAGER, GL AF SADAIE, MR HAGER, GL TI ACTIVATION OF DORMANT HIV-1 IS ASSOCIATED WITH DEVELOPMENTALLY PROGRAMMED CELL-DEATH SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NIDR,ORAL MED LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S63 EP S63 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600162 ER PT J AU SAMANIEGO, F KAO, V ZON, G GALLO, RC ENSOLI, B AF SAMANIEGO, F KAO, V ZON, G GALLO, RC ENSOLI, B TI INFLAMMATORY CYTOKINES INCREASED IN HIV-1-INFECTED INDIVIDUALS STIMULATE AIDS-KAPOSIS SARCOMA (AIDS-KS) CELL-GROWTH AND THIS EFFECT IS BLOCKED BY ANTISENSE OLIGONUCLEOTIDES AGAINST BASIC FIBROBLAST GROWTH-FACTOR (BFGF) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LYNX THERAPEUT INC,FOSTER CITY,CA 94404. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S53 EP S53 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600127 ER PT J AU SAVILLE, MW TOSATO, G TAGA, K FOLI, A BRODER, S YARCHOAN, R AF SAVILLE, MW TOSATO, G TAGA, K FOLI, A BRODER, S YARCHOAN, R TI INHIBITION OF HIV REPLICATION IN MONOCYTE/MACROPHAGES (M/M) BY INTERLEUKIN-10 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. US FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S27 EP S27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600038 ER PT J AU SCHLOM, J KANTOR, J ABRAMS, S TSANG, A DOBRZANSKI, M AF SCHLOM, J KANTOR, J ABRAMS, S TSANG, A DOBRZANSKI, M TI RECOMBINANT VACCINES FOR THE ACTIVE SPECIFIC IMMUNOTHERAPY OF HUMAN CANCER SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S58 EP S58 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600147 ER PT J AU SECCHIERO, P BERNEMAN, ZN GALLO, RC LUSSO, P AF SECCHIERO, P BERNEMAN, ZN GALLO, RC LUSSO, P TI CHARACTERIZATION OF 2 NOVEL ISOLATES OF HUMAN HERPESVIRUS-7 (HHV-7) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S124 EP S124 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600379 ER PT J AU SIMPSON, RM LENO, M SAWASDIKOSOL, S ZHAO, TM KINDT, TJ AF SIMPSON, RM LENO, M SAWASDIKOSOL, S ZHAO, TM KINDT, TJ TI A RABBIT HTLV-I LETHAL LEUKEMOGENIC LINE AND VIRUS ISOLATE CAUSE LYMPHOCYTE APOPTOSIS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S121 EP S121 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600367 ER PT J AU SPOUGE, JL NARA, PL MERGES, MJ LAYNE, SP AF SPOUGE, JL NARA, PL MERGES, MJ LAYNE, SP TI VIRAL MULTIPLICITY OF ADSORPTION - A QUANTITATIVE ANALOG OF TARGET-CELL MULTIPLICITY INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NCI,FREDERICK CANC RES & DEV CTR,LTCB,VIRUS BIOL SECT,FREDERICK,MD 21702. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S67 EP S67 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600176 ER PT J AU SUN, D WEICHOLD, FF LUSSO, P CROWLEY, R AGRAWAL, S ZAMECNIK, P GALLO, RC LISZIEWICZ, J AF SUN, D WEICHOLD, FF LUSSO, P CROWLEY, R AGRAWAL, S ZAMECNIK, P GALLO, RC LISZIEWICZ, J TI ANTISENSE OLIGONUCLEOTIDE PHOSPHOROTHIOATES INHIBIT PRIMARY HIV-1 ISOLATES IN PERIPHERIAL BLOOD-LYMPHOCYTES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S32 EP S32 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600056 ER PT J AU THIERRY, AR GALLO, RC LISZIEWICZ, J AF THIERRY, AR GALLO, RC LISZIEWICZ, J TI LIPOSOME-MEDIATED GENE-TRANSFER SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI thierry, alain/F-9492-2014 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S32 EP S32 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600055 ER PT J AU THOMSON, MM TUDORWILLIAMS, D ROBERTSON, J RADTKE, M GALLO, RC KLOTMAN, ME AF THOMSON, MM TUDORWILLIAMS, D ROBERTSON, J RADTKE, M GALLO, RC KLOTMAN, ME TI COMPETITIVE RT-PCR FOR QUANTITATION OF HIV-1 TAT RNAS BY USING FLUORESCENTLY LABELED PRIMERS AND POLYACRYLAMIDE DENATURING GELS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. APPL BIOSYST INC,FOSTER CITY,CA. RI klotman, mary/A-1921-2016 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S68 EP S68 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600182 ER PT J AU THOMSON, MM LI, G ZON, G GALLO, RC KLOTMAN, ME AF THOMSON, MM LI, G ZON, G GALLO, RC KLOTMAN, ME TI RAPID SCREENING OF PHOSPHOROTHIOATE ANTISENSE OLIGONUCLEOTIDES (S-ODNS) DIRECTED AGAINST HIV-1 - SEQUENCE-SPECIFIC DOSE-RESPONSE CURVES WITH S-ODNS TARGETED TO RRE AND REV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LYNX THERAPEUT,FOSTER CITY,CA. RI klotman, mary/A-1921-2016 NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S31 EP S31 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600053 ER PT J AU VERMUND, SH FISCHER, RD WEBER, DJ SHEON, AR HOFF, R AF VERMUND, SH FISCHER, RD WEBER, DJ SHEON, AR HOFF, R TI RESEARCH PRIORITIES FOR HIV PREVENTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID,DIV AIDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S106 EP S106 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600317 ER PT J AU VITEK, CR GRACIA, F FUKUDA, K GREEN, D GIUSTI, R KHABBAZ, R LEVINE, P KAPLAN, J BLATTNER, W AF VITEK, CR GRACIA, F FUKUDA, K GREEN, D GIUSTI, R KHABBAZ, R LEVINE, P KAPLAN, J BLATTNER, W TI EVIDENCE FOR SEXUAL AND MOTHER-TO-CHILD TRANSMISSION OF HTLV-II AMONG GUAYMI INDIANS, PANAMA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 CDC,RETROVIRUS DIS BRANCH,ATLANTA,GA. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD. GORGAS MEM LAB,PANAMA CITY,PANAMA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S119 EP S119 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600360 ER PT J AU VOEVODIN, A FRANCHINI, G KORALNIK, I SCHATZL, H CHIKOBAVA, M SAMILCHUK, E BOERI, E AF VOEVODIN, A FRANCHINI, G KORALNIK, I SCHATZL, H CHIKOBAVA, M SAMILCHUK, E BOERI, E TI INTERSPECIES TRANSMISSION OF STLV-1 RESULTED IN THE OUTBREAK OF MALIGNANT-LYMPHOMA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 KUWAIT UNIV,FAC MED,KUWAIT,KUWAIT. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD. UNIV CALIF SAN FRANCISCO,DEPT NEUROL,SAN FRANCISCO,CA 94143. MOSCOW MED PRIMATOL INST,MOSCOW,RUSSIA. RI Schatzl, Hermann/G-4958-2011 NR 0 TC 2 Z9 2 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 AUG PY 1994 VL 10 SU 1 BP S121 EP S121 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600366 ER PT J AU WANG, LM MYERS, MG SUN, XJ AARONSON, SA WHITE, M PIERCE, JH AF WANG, LM MYERS, MG SUN, XJ AARONSON, SA WHITE, M PIERCE, JH TI EXPRESSION OF IRS-1 RESTORES INSULIN-MEDIATED AND IL-4-MEDIATED MITOGENESIS IN HEMATOPOIETIC-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,BOSTON,MA 02215. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S101 EP S101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600298 ER PT J AU WATERS, DJ WILSON, C MILEY, W ARTHUR, L BLATTNER, W REITZ, M AF WATERS, DJ WILSON, C MILEY, W ARTHUR, L BLATTNER, W REITZ, M TI A RAPID, WORKING ADHERENT CELL ASSAY FOR THE DETECTION AND QUANTITATION OF INFECTIOUS HIV-1 AND HIV-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NCI,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S67 EP S67 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600175 ER PT J AU WATKINS, BA VERONESE, F DAVIS, AE REITZ, MS AF WATKINS, BA VERONESE, F DAVIS, AE REITZ, MS TI RECOMBINANT ANTIBODY FRAGMENTS TO HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S73 EP S73 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600198 ER PT J AU WEICHOLD, FF SUN, D ZEMAN, RA AGRAWAL, S ZAMECMIK, PC GALLO, RC LISZIEWICZ, J AF WEICHOLD, FF SUN, D ZEMAN, RA AGRAWAL, S ZAMECMIK, PC GALLO, RC LISZIEWICZ, J TI INHIBITION OF HIV-1 REPLICATION BY ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES IN CULTURED HUMAN MACROPHAGES AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S32 EP S32 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600054 ER PT J AU WEISS, SH CLARICI, M MAYUR, RK DENNY, TN QUIRINALE, JE HEWLETT, IK EPSTEIN, J PALUMBO, PE BERZOFSKY, JA SHEARER, GM AF WEISS, SH CLARICI, M MAYUR, RK DENNY, TN QUIRINALE, JE HEWLETT, IK EPSTEIN, J PALUMBO, PE BERZOFSKY, JA SHEARER, GM TI IMMUNOLOGICAL AND VIROLOGICAL RESPONSES TO HIV EXPOSURE AMONG A HIGH-RISK BUT LONG-TERM HIV ANTIBODY NEGATIVE COHORT OF DRUG-USERS, AND INTERACTIONS WITH HTLV-II SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. US FDA,BETHESDA,MD 20014. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S106 EP S106 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600314 ER PT J AU WEISSMAN, D ZHOU, LJ TEDDER, TF FAUCI, AS AF WEISSMAN, D ZHOU, LJ TEDDER, TF FAUCI, AS TI 2 POPULATIONS OF CELLS WITH A DENDRITIC MORPHOLOGY EXIST IN PERIPHERAL-BLOOD SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NIAID,LIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 10 SU 1 BP S72 EP S72 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600194 ER PT J AU YARCHOAN, R SAVILLE, MW PLUDA, JM FOLI, A BAILEY, J WILSON, W BRODER, S AF YARCHOAN, R SAVILLE, MW PLUDA, JM FOLI, A BAILEY, J WILSON, W BRODER, S TI APPROACHES TO THE DEVELOPMENT OF THERAPY FOR KAPOSISS SARCOMA (KS) - A REPORT ON ONGOING STUDIES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract ID GROWTH C1 NCI,OFF DIRECTOR,BETHESDA,MD. NCI,MED BRANCH,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1994 VL 10 SU 1 BP S52 EP S52 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PF066 UT WOS:A1994PF06600125 ER PT J AU ALLEN, JP LITTEN, RZ ANTON, RF CROSS, GM AF ALLEN, JP LITTEN, RZ ANTON, RF CROSS, GM TI CARBOHYDRATE-DEFICIENT TRANSFERRIN AS A MEASURE OF IMMODERATE DRINKING - REMAINING ISSUES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CDT; ANION-EXCHANGE CHROMATOGRAPHY; ISOELECTRIC FOCUSING; SCREENING; BIOCHEMICAL MARKERS ID ANION-EXCHANGE CHROMATOGRAPHY; MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE; ALCOHOL-CONSUMPTION; DESIALYLATED TRANSFERRIN; SERUM TRANSFERRIN; ABNORMAL MICROHETEROGENEITY; LABORATORY MARKERS; LIVER-DISEASES; HEAVY DRINKING; TF-INDEX AB A growing body of investigations demonstrate that elevated levels of carbohydrate-deficient transferrin (CDT) effectively distinguishes alcoholics recently consuming large amounts of alcohol from light social drinkers or teetotalers. Nevertheless, important questions still remain concerning the value of CDT as a more generalized marker of alcohol consumption. Most important, the nature of the drinking pattern, including quantity and frequency, necessary to raise levels of CDT significantly remains unclear. Neither has research convincingly demonstrated that CDT is as accurate a marker for women, young adults, or non-Caucasian ethnic groups as for White, middle-aged men. Whereas CDT might serve as a useful outcome measure in trials of alcoholism treatment effectiveness, current research suggests that CDT is of limited value in identifying problematic drinking in general medical or community settings in which a broad continuum of drinkers is represented. Combining CDT with other biochemical or self-report screening measures may, however, improve sensitivity in these contexts. At present, the most accurate laboratory technique to detect CDT seems to be isoelectric focusing. Additional research, however, is needed to resolve the issue of whether CDT is best quantitated as a simple value or if its ratio to total transferrin or non-CDT results in higher predictive validity. C1 MED UNIV S CAROLINA,INST PSYCHIAT,COLUMBIA,SC. USA,OFF SURGEON GEN,WASHINGTON,DC 20310. RP ALLEN, JP (reprint author), NIAAA,DIV CLIN & PREVENT RES,TREATMENT RES BRANCH,ROOM 14C-20,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 60 TC 153 Z9 156 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1994 VL 18 IS 4 BP 799 EP 812 DI 10.1111/j.1530-0277.1994.tb00043.x PG 14 WC Substance Abuse SC Substance Abuse GA PC774 UT WOS:A1994PC77400006 PM 7978088 ER PT J AU TSUJI, H VENDITTI, FJ EVANS, JC LARSON, MG LEVY, D AF TSUJI, H VENDITTI, FJ EVANS, JC LARSON, MG LEVY, D TI THE ASSOCIATIONS OF LEVELS OF SERUM POTASSIUM AND MAGNESIUM WITH VENTRICULAR PREMATURE COMPLEXES (THE FRAMINGHAM HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SYSTEMIC HYPERTENSION; ECTOPIC ACTIVITY; RISK FACTOR; ARRHYTHMIAS; DIURETICS AB There are conflicting data regarding the impact of serum potassium and magnesium levels on susceptibility to ventricular premature complexes (VPCs) in the clinical setting. The associations of serum potassium and magnesium levels with the prevalence of complex or frequent (>30/hour, multiform or repetitive) VPCs were examined after adjusting for age, sex, smoking, caffeinated coffee consumption, alcohol consumption, and left ventricular mass in Framingham Offspring Study subjects who were free of clinically apparent heart disease. There were 3,327 eligible subjects (mean age 44 years). Complex or frequent VPCs were present in 183 subjects (5.5%). When age-adjusted prevalences of complex or frequent VPCs were compared among quartiles of serum potassium and magnesium using a trend test, lower potassium (p = 0.002) and lower magnesium (p = 0.010) levels were associated with higher prevalence rates of arrhythmia. In logistic regression analyses that included potassium and magnesium simultaneously, potassium (p = 0.0021) and magnesium (p = 0.0311) levels were inversely associated with the occurrence of complex or frequent VPCs after adjustment for age, sex, smoking, coffee and alcohol consumption, diuretic use, and systolic blood pressure. These associations remained significant after accounting for left ventricular mass. A 1 SD decrement in potassium (0.48 mEq/liter) or magnesium (0.16 mEq/liter) level was associated with a 27% (95% confidence interval 6% to 51%) and a 20% (95% confidence interval 3% to 41%) greater odds of complex or frequent VPCs, respectively. Lower levels of serum potassium and magnesium were concurrently associated with higher prevalence rates of ventricular arrhythmias. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA 01701 USA. LAHEY CLIN MED CTR, BURLINGTON, MA 01803 USA. BOSTON UNIV, SCH MED, DIV PREVENT MED, BOSTON, MA 02118 USA. BETH ISRAEL HOSP, DIV CARDIOL, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV CLIN EPIDEMIOL, BOSTON, MA 02215 USA. NHLBI, BETHESDA, MD 20892 USA. NR 30 TC 52 Z9 55 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1994 VL 74 IS 3 BP 232 EP 235 DI 10.1016/0002-9149(94)90362-X PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NY796 UT WOS:A1994NY79600005 PM 7518645 ER PT J AU FURBERG, CD PSATY, BM MANOLIO, TA GARDIN, JM SMITH, VE RAUTAHARJU, PM AF FURBERG, CD PSATY, BM MANOLIO, TA GARDIN, JM SMITH, VE RAUTAHARJU, PM TI PREVALENCE OF ATRIAL-FIBRILLATION IN ELDERLY SUBJECTS (THE CARDIOVASCULAR HEALTH STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID POPULATION; STROKE; ABNORMALITIES; OLDER AB Atrial fibrillation (AF) is a common arrhythmia in elderly persons and a common cause of embolic stroke. Most studies of the prevalence and correlates of AF have used selected, hospital-based populations. The Cardiovascular Health Study is a population-based, longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged greater than or equal to 65 years. AF was diagnosed in 4.8% of women and in 6.2% of men at the baseline examination, and prevalence was strongly associated with advanced age in women. Prevalence of AF was 9.1% in men and women with clinical cardiovascular disease, 4.6% in patients with evidence of subclinical but no clinical cardiovascular disease, and only 1.6% in subjects with neither clinical nor subclinical cardiovascular disease. A history of congestive heart failure, valvular heart disease and stroke, echocardiographic evidence of enlarged left atrial dimension, abnormal mitral or aortic valve function, treated systemic hypertension, and advanced age were independently associated with the prevalence of AF. The low prevalence of AF in the absence of clinical and subclinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called ''lone atrial fibrillation'' in the elderly. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV & MED,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV CALIF IRVINE,DEPT MED,ORANGE,CA 92668. ALBANY MED COLL,DEPT MED,ALBANY,NY. UNIV ALBERTA,EPICORE CTR,DIV CARDIOL,EDMONTON,AB,CANADA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 29 TC 654 Z9 709 U1 1 U2 5 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 AUG 1 PY 1994 VL 74 IS 3 BP 236 EP 241 DI 10.1016/0002-9149(94)90363-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NY796 UT WOS:A1994NY79600006 PM 8037127 ER PT J AU ATKINSON, RL HUBBARD, VS AF ATKINSON, RL HUBBARD, VS TI REPORT ON THE NIH WORKSHOP ON PHARMACOLOGICAL TREATMENT OF OBESITY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material DE OBESITY; PHARMACOLOGICAL AGENTS; DRUGS; WEIGHT LOSS; OBESITY COMPLICATIONS; ADRENERGIC AGENTS; SEROTONINERGIC AGENTS; SYMPATHETIC NERVOUS SYSTEM; FOOD AND DRUG ADMINISTRATION ID TERM WEIGHT CONTROL; ADRENOCEPTOR AGONIST BRL-26830A; FENFLURAMINE PLUS PHENTERMINE; BEHAVIOR-MODIFICATION; CALORIC RESTRICTION; OPEN-LABEL; DEXFENFLURAMINE; PLACEBO; MEDICATION; APPETITE AB A National Institutes of Health workshop on pharmacologic treatment of obesity concluded that pharmacologic agents may be effective in reducing body weight over an extended period of time. Drugs should be used as only one component of a comprehensive weight-reduction program, and additional research is needed on the long-term efficacy and safety of drugs for obesity, and especially for combinations of drugs. Improvement in comorbidities and risk factors of obesity should be used along with weight reduction as an outcome measure in clinical trials. Industry, professional societies, and governmental agencies should work together to explore the potential for drugs for obesity and to reassess the regulatory and administrative controls on the use of currently available drugs for obesity and on the approval process for future drugs. C1 UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53706. NIDDK,NUTR SCI BRANCH,BETHESDA,MD. RP ATKINSON, RL (reprint author), UNIV WISCONSIN,DEPT MED,NUTR SCI BLDG,1415 LINDEN DR,MADISON,WI 53706, USA. NR 33 TC 33 Z9 33 U1 0 U2 0 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 AUG PY 1994 VL 60 IS 2 BP 153 EP 156 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NY101 UT WOS:A1994NY10100001 PM 7913290 ER PT J AU HALLFRISCH, J MULLER, DC SINGH, VN AF HALLFRISCH, J MULLER, DC SINGH, VN TI VITAMIN-A AND VITAMIN-E INTAKES AND PLASMA-CONCENTRATIONS OF RETINOL, BETA-CAROTENE, AND ALPHA-TOCOPHEROL IN MEN AND WOMEN OF THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE RETINOL; CAROTENE; TOCOPHEROL; ANTIOXIDANTS; AGING; VITAMIN INTAKE ID HEALTHY ELDERLY POPULATION; NUTRITIONAL-STATUS; A SUPPLEMENTATION; BINDING-PROTEIN; SERUM RETINOL; CANCER; RISK; CATARACT; DIETARY; ESTERS AB Antioxidants have been linked to protection against degenerative diseases associated with aging. Plasma concentrations were determined for and 7-d diet records collected from 200 women and 231 men aged 20-95 y who took part in the Baltimore Longitudinal Study of Aging. Men consumed more vitamin A from animal and less from vegetable sources than did women. These sex differences are reflected in plasma concentrations of retinol and beta-carotene. About 20% of subjects had vitamin A intakes less than recommended dietary allowances; however, no men and only two women had marginal plasma retinol (< 0.35 mu mol/L) concentrations. Older people had higher plasma alpha-tocopherol, which correlated with total intake. Forty-two men and 35 women had plasma alpha-tocopherol concentrations that were considered marginal. Sex differences in sources of dietary and plasma vitamin A may have consequences in relation to aging and longevity. Apparent marginal intakes and plasma concentrations of vitamin E need to be further examined to determine effects on health status. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. RP HALLFRISCH, J (reprint author), USDA,BELTSVILLE HUMAN NUTR RES CTR,CARBOHYDRATE NUTR LAB,BLDG 307,ROOM 323,BELTSVILLE,MD 20705, USA. NR 48 TC 74 Z9 75 U1 0 U2 2 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 AUG PY 1994 VL 60 IS 2 BP 176 EP 182 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NY101 UT WOS:A1994NY10100005 PM 8030594 ER PT J AU INSULL, W SILVERS, A HICKS, L PROBSTFIELD, JL AF INSULL, W SILVERS, A HICKS, L PROBSTFIELD, JL TI PLASMA-LIPID EFFECTS OF 3 COMMON VEGETABLE-OILS IN REDUCED-FAT DIETS OF FREE-LIVING ADULTS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE DIETARY FATS; FATTY ACIDS; UNSATURATED FATTY ACIDS; MONOUNSATURATED FATTY ACIDS; POLYUNSATURATED FATTY ACIDS; LIPOPROTEINS; REDUCED-FAT DIETS; PHYTOSTEROL; TRANS FATTY ACID ID DENSITY-LIPOPROTEIN-CHOLESTEROL; NORTH-AMERICAN POPULATIONS; CORONARY HEART-DISEASE; RESEARCH CLINICS PREVALENCE; POLY-UNSATURATED FAT; SERUM-LIPOPROTEINS; MONOUNSATURATED FAT; LOWERING DIETS; LINOLEIC-ACID; PLANT STEROLS AB We compared plasma lipid changes due to the polyunsaturated fatty acids (PUFAs) in partially hydrogenated soybean oil, corn oil, and sunflower oil fed in reduced-fat diets (22-26% of total energy). Each oil was the dominant fat in isoenergetic diets of centrally prepared foods consumed by 26 male and 35 female normolipidemic, free-living individuals. Test diets were consumed double-blind, alternating with self-selected diets for 5 wk each. The ranges of proportions of total fat were: 4.7-9.7% polyunsaturated fat, 8.9-14.2% monounsaturated fat and 5.4-7.4% saturated fat. All three diets lowered (P < 0.0001) total cholesterol(11%), LDL cholesterol (13%), and HDL cholesterol (10%), without triglyceride changes. We conclude that PUFAs at approximate to 6% of total energy result in clinically relevant plasma cholesterol-lowering and that the proportion of polyunsaturated fat must be an important consideration when planning reduced-fat, reduced-saturated-fat diets. C1 BAYLOR COLL MED,METHODIST HOSP,DEPT MED,LIPID RES CLIN,HOUSTON,TX 77030. ELECT POWER RES INST,PALO ALTO,CA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HV 1-2156] NR 65 TC 7 Z9 7 U1 0 U2 0 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 AUG PY 1994 VL 60 IS 2 BP 195 EP 202 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NY101 UT WOS:A1994NY10100008 PM 8030596 ER PT J AU YONG, LC FORMAN, MR BEECHER, GR GRAUBARD, BI CAMPBELL, WS REICHMANN, ME TAYLOR, PR LANZA, E HOLDEN, JM JUDD, JT AF YONG, LC FORMAN, MR BEECHER, GR GRAUBARD, BI CAMPBELL, WS REICHMANN, ME TAYLOR, PR LANZA, E HOLDEN, JM JUDD, JT TI RELATIONSHIP BETWEEN DIETARY-INTAKE AND PLASMA-CONCENTRATIONS OF CAROTENOIDS IN PREMENOPAUSAL WOMEN - APPLICATION OF THE USDA NCI CAROTENOID FOOD-COMPOSITION DATABASE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE CAROTENOIDS; DIETARY ASSESSMENT; PLASMA ID ALPHA-TOCOPHEROL LEVELS; SERUM BETA-CAROTENE; MIDDLE-AGED MEN; VITAMIN-E; FREQUENCY QUESTIONNAIRE; ALCOHOL-CONSUMPTION; CANCER; RETINOL; RISK; VEGETABLES AB The diet-plasma relationships for carotenoids were examined in a group of 98 nonsmoking premenopausal women who participated in the cross-sectional phase of the National Cancel Institute (NCI)-US Department of Agriculture (USDA) diet study on alcohol-hormone metabolism, 1988-90. With use of the newly developed USDA-NCI carotenoid food-composition database, the mean daily intakes of carotenoids were significantly higher when estimated from the food-frequency questionnaire (FFQ) than from the 7-d diet records. Lycopene (($) over bar x = 0.58 mmol/L), lutein plus zeaxanthin (($) over bar x = 0.46 mmol/L), and beta-carotene (($) over bar x = 0.34 mmol/L) were the major plasma carotenoids. After adjustment for body mass index, energy and alcohol intakes, and total plasma cholesterol concentration, the following significant correlations (P < 0.05) were observed between the diet record and the FFQ-estimated carotenoid intakes and their respective plasma concentrations: alpha-carotene (r = 0.58 vs 0.49), beta-carotene (r = 0.51 vs 0.49), beta-cryptoxanthin (r = 0.49 vs 0.36). lutein plus zeaxanthin (r = 0.31 vs 0.37), lycopene (r = 0.50 vs 0.26), and total carotenoids (r = 0.57 vs 0.49). These data indicate that plasma carotenoid concentrations are reflective of dietary intake, but the magnitude of the con elation varies depending on the specific carotenoid and on the dietary assessment tool. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,ROCKVILLE,MD. USDA,CTR AGR RES SERV,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. RP YONG, LC (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,EPN 211,ROCKVILLE,MD 20892, USA. NR 45 TC 82 Z9 83 U1 1 U2 4 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 AUG PY 1994 VL 60 IS 2 BP 223 EP 230 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NY101 UT WOS:A1994NY10100012 PM 8030600 ER PT J AU JOHNSTONE, PAS MICAN, JM METCALFE, DD DELANEY, TF AF JOHNSTONE, PAS MICAN, JM METCALFE, DD DELANEY, TF TI RADIOTHERAPY OF REFRACTORY BONE PAIN DUE TO SYSTEMIC MAST-CELL DISEASE SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE MAST CELL DISEASE; RADIOTHERAPY; PAIN; PALLIATION ID RADIATION-THERAPY; MASTOCYTOSIS; MANAGEMENT AB Systemic mastocytosis is a rare disease characterized by mast cell infiltration of organs. Bony pain is present in up to 28% of cases and is frequently chronic and difficult to palliate. Historical attempts at pain control have exclusively involved medical therapy. We report three cases of refractory bone pain in two patients with advanced systemic mast cell disease and associated bony involvement, which were treated with radiotherapy. This report represents some of the first uses of radiotherapy in this disease. Two patients with a primary diagnosis of systemic mastocytosis and bony pain unresponsive to medical therapy were referred for palliative radiotherapy. In the first case, referral was made because of a painful thoracolumbar spine and left shoulder, and in the second, for bilateral lower extremity pain. Patients were irradiated on megavoltage equipment to 30 Gy in 200 and 300 cGy daily fractions. For the first patient, treatment reduced pain scores from 8/10 (severe) to 3-4/10 (moderate) by 1 month posttreatment, with subsequent varying pain until his death 4 months after his second treatment. The second patient achieved pain relief from 10/10 pretreatment to 1-2/10 while on treatment. This proved durable for 9 months until her death due to disease progression. The first patient had a slight exacerbation of his thrombocytopenia during his initial treatment, but otherwise neither patient experienced any acute complications from the radiation treatments. When patients with advanced systemic mastocytosis require large narcotic doses for incomplete bone pain control associated with demonstrable bony involvement, the relatively slight risks of palliative radiation to bone may be favorably weighed against the likelihood of pain relief. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NR 7 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 1994 VL 17 IS 4 BP 328 EP 330 DI 10.1097/00000421-199408000-00009 PG 3 WC Oncology SC Oncology GA NZ450 UT WOS:A1994NZ45000009 PM 7519391 ER PT J AU SHERMAN, ME SCHIFFMAN, MH LORINCZ, AT MANOS, MM SCOTT, DR KURMAN, RJ KIVIAT, NB STOLER, M GLASS, AG RUSH, BB AF SHERMAN, ME SCHIFFMAN, MH LORINCZ, AT MANOS, MM SCOTT, DR KURMAN, RJ KIVIAT, NB STOLER, M GLASS, AG RUSH, BB TI TOWARD OBJECTIVE QUALITY ASSURANCE IN CERVICAL CYTOPATHOLOGY - CORRELATION OF CYTOPATHOLOGIC DIAGNOSES WITH DETECTION OF HIGH-RISK HUMAN PAPILLOMAVIRUS TYPES SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE; THE BETHESDA SYSTEM; CERVICAL CYTOPATHOLOGY; CERVICAL INTRAEPITHELIAL NEOPLASIA; CONDYLOMATOUS ATYPIA; HUMAN PAPILLOMAVIRUS; KOILOCYTOSIS; KOILOCYTOTIC ATYPIA; MILD DYSPLASIA; QUALITY ASSURANCE; REPRODUCIBILITY; SQUAMOUS INTRAEPITHELIAL LESION ID ATYPICAL PAPANICOLAOU SMEARS; INTRAEPITHELIAL NEOPLASIA; INFLAMMATORY ATYPIA; SQUAMOUS CELLS; COLPOSCOPY; CYTOLOGY AB Using The Bethesda System, five pathologists independently diagnosed 200 smears that originally had been classified as ''atypical,'' and the results were correlated with concurrent detection of human papillomavirus (HPV) DNA by Southern analysis and by polymerase chain reaction amplification. The smears were reclassified as benign reactive changes (negative), atypical squamous cells of undetermined significance, or squamous intraepithelial lesion (SIL). Exact five-way cytologic agreement was achieved in only 29% of smears, and no slide was diagnosed as atypical squamous cells of undetermined significance by all reviewers. The detection of high-risk types of HPV correlated strongly with the likelihood of a diagnosis of squamous intraepithelial lesion. High-risk HPV types were detected in approximately 60% of smears reclassified as squamous intraepithelial lesion compared with 30% of those reclassified as atypical squamous cells of undetermined significance and 10% of negative smears (P < .001). Every smear unanimously diagnosed by the panel as squamous intraepithelial lesion was associated with detectable HPV DNA, mainly of high-risk types. Low-risk HPV DNA types were found with similar frequency in all diagnostic categories assigned by the reviewers. Based on the consistent relation between high-risk HPV detection and diagnoses according to the Bethesda System, the authors conclude that HPV testing may have an important role in quality assurance in cervical cytopathology. C1 JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. DIGENE DIAGNOST INC,SILVER SPRING,MD. KAISER PERMANENTE,DEPT PATHOL,PORTLAND,OR. UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. CLEVELAND CLIN FDN,DEPT PATHOL,CLEVELAND,OH 44195. CETUS CORP,EMERYVILLE,CA. NR 20 TC 167 Z9 169 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 1994 VL 102 IS 2 BP 182 EP 187 PG 6 WC Pathology SC Pathology GA PA500 UT WOS:A1994PA50000009 PM 8042586 ER PT J AU SHERMAN, JB RABEN, N NICASTRI, C ARGOV, Z NAKAJIMA, H ADAMS, EM ENG, CM COWAN, TM PLOTZ, PH AF SHERMAN, JB RABEN, N NICASTRI, C ARGOV, Z NAKAJIMA, H ADAMS, EM ENG, CM COWAN, TM PLOTZ, PH TI COMMON MUTATIONS IN THE PHOSPHOFRUCTOKINASE-M GENE IN ASHKENAZI JEWISH PATIENTS WITH GLYCOGENESIS-VII - AND THEIR POPULATION FREQUENCY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; SOMATIC-CELL HYBRIDS; SINGLE-BASE CHANGES; MESSENGER-RNA; REGIONAL ASSIGNMENT; NONSENSE MUTATIONS; DNA FRAGMENTS; GC-CLAMP; MUSCLE; DEFICIENCY AB Phosphofructokinase (PFK) catalyzes the rate-limiting step of glycolysis. Deficiency of the muscle enzyme is manifested by exercise intolerance and a compensated hemolytic anemia. Case reports of this autosomal recessive disease suggest a predominance in Ashkenazi Jews in the United States. We have explored the genetic basis for this illness in nine affected families and surveyed the normal Ashkenazi population for the mutations we have found. Genomic DNA was amplified using PCR, and denaturing gradient-gel electrophoresis was used to localize exons with possible mutations. The polymorphic exons were sequenced or digested with restriction enzymes. A previously described splicing mutation, Delta 5, accounted for 11 (61%) of 18 abnormal alleles in the nine families. A single base deletion leading to a frameshift mutation in exon 22 (Delta C-22) was found in six of seven alleles. A third mutation, resulting in a nonconservative amino acid substitution in exon 4, accounted for the remaining allele. Thus, three mutations could account for all illness in this group, and two mutations could account for 17 of 18 alleles. In screening 250 normal Ashkenazi individuals for all three mutations, we found only one Delta 5 allele. Clinical data revealed no correlation between the particular mutations and symptoms, but male patients were more symptomatic than females, and only males had frank hemolysis and hyperuricemia. Because PFK deficiency in Ashkenazi Jews is caused by a limited number of mutations, screening genomic DNA from peripheral blood for the described mutations in this population should enable rapid diagnosis without muscle biopsy. C1 NIAMS,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT NEUROL,IL-91010 JERUSALEM,ISRAEL. CUNY MT SINAI SCH MED,DEPT HUMAN GENET,NEW YORK,NY 10029. UNIV MARYLAND,SCH MED,DIV HUMAN GENET,BALTIMORE,MD 21201. NR 41 TC 54 Z9 54 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1994 VL 55 IS 2 BP 305 EP 313 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA NZ336 UT WOS:A1994NZ33600011 PM 8037209 ER PT J AU MACCOLLIN, M RAMESH, V JACOBY, LB LOUIS, DN RUBIO, MP PULASKI, K TROFATTER, JA SHORT, MP BOVE, C ELDRIDGE, R PARRY, DM GUSELLA, JF AF MACCOLLIN, M RAMESH, V JACOBY, LB LOUIS, DN RUBIO, MP PULASKI, K TROFATTER, JA SHORT, MP BOVE, C ELDRIDGE, R PARRY, DM GUSELLA, JF TI MUTATIONAL ANALYSIS OF PATIENTS WITH NEUROFIBROMATOSIS-2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; TUMOR-SUPPRESSOR; DISEASE AB Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins, which we have named merlin. To define the molecular basis of NF2 in affected individuals, we have used SSCP analysis to scan the exons of the NF2 gene from 33 unrelated patients with NF2. Twenty unique SSCP variants were seen in 21 patients; 10 of these individuals were known to be the only affected person in their kindred, while 7 had at least one other known affected relative. In all cases in which family members were available, the SSCP variant segregated with the disease; comparison of sporadic cases with their parents confirmed the de novo variants. DNA sequence analysis revealed that 19 of the 20 variants observed are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. A single patient carried a 3-bp deletion removing a phenylalanine residue. We conclude that the majority of NF2 patients carry an inactivating mutation of the NF2 gene and that neutral polymorphism in the gene is rare. C1 MASSACHUSETTS GEN HOSP E,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,NEUROSURG SERV,BOSTON,MA. MASSACHUSETTS GEN HOSP E,MOLEC NEUROONCOL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. US PHS,BETHESDA,MD. NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Rubio, Mari-Paz/K-4364-2014 OI Rubio, Mari-Paz/0000-0003-3963-5903 FU NHGRI NIH HHS [HG00317]; NIDCD NIH HHS [NIDCD DC01291]; NINDS NIH HHS [NS24279] NR 19 TC 101 Z9 104 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1994 VL 55 IS 2 BP 314 EP 320 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NZ336 UT WOS:A1994NZ33600012 PM 7913580 ER PT J AU HEINEMAN, EF COCCO, P GOMEZ, MR DOSEMECI, M STEWART, PA HAYES, RB ZAHM, SH THOMAS, TL BLAIR, A AF HEINEMAN, EF COCCO, P GOMEZ, MR DOSEMECI, M STEWART, PA HAYES, RB ZAHM, SH THOMAS, TL BLAIR, A TI OCCUPATIONAL EXPOSURE TO CHLORINATED ALIPHATIC-HYDROCARBONS AND RISK OF ASTROCYTIC BRAIN CANCER SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE BRAIN CANCER; GLIOMA; SOLVENTS; METHYLENE CHLORIDE; TETRACHLOROETHYLENE ID RETROSPECTIVE COHORT MORTALITY; DRY CLEANING WORKERS; PRIMARY LIVER-CANCER; METHYLENE-CHLORIDE; UNITED-STATES; CASE-REFERENT; TUMORS; TRICHLOROETHYLENE; CARCINOGENS; INDUSTRY AB Chlorinated aliphatic hydrocarbons (CAHs) were evaluated as potential risk factors for astrocytic brain tumors. Job-exposure matrices for six individual CAHs and for the general class of organic solvents were applied to data from a case-control study of brain cancer among white men. The matrices indicated whether the CAHs were likely to have been used in each industry and occupation by decade (1920-1980), and provided estimates of probability and intensity of exposure for ''exposed'' industries and occupations. Cumulative exposure indices were calculated for each subject. Associations of astrocytic brain cancer were observed with likely exposure to carbon tetrachloride, methylene chloride, tetrachloroethylene, and trichloroethylene, but were strongest for methylene chloride. Exposure to chloroform or methyl chloroform showed little indication of an association with brain cancer. Risk of astrocytic brain tumors increased with probability and average intensity of exposure, and with duration of employment in jobs considered exposed to methylene chloride, but not with a cumulative exposure score. These trends could not be explained by exposures to the other solvents. (C) 1994 Wiley-Liss, Inc.* C1 NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. RI Zahm, Shelia/B-5025-2015 NR 59 TC 66 Z9 66 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 1994 VL 26 IS 2 BP 155 EP 169 DI 10.1002/ajim.4700260203 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NY093 UT WOS:A1994NY09300002 PM 7977393 ER PT J AU GOMEZ, MR COCCO, P DOSEMECI, M STEWART, PA AF GOMEZ, MR COCCO, P DOSEMECI, M STEWART, PA TI OCCUPATIONAL EXPOSURE TO CHLORINATED ALIPHATIC-HYDROCARBONS - JOB EXPOSURE MATRIX SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE EXPOSURE ASSESSMENT METHODS; CHLORINATED SOLVENTS; SIC; SOC; FALSE POSITIVE EXPOSURE ASSESSMENTS ID MORTALITY; WORKERS; RISK AB A job exposure matrix combining features to increase the accuracy of exposure assessment was developed to evaluate cancer risks from workplace exposures to six chlorinated aliphatic hydrocarbons (CAHs). A detailed description of the matrix is provided to satisfy the need for more in-depth discussion of exposure assessment methods than is typical in today's epidemiologic literature. The matrix assigns semiquantitative estimates of the probability and intensity of exposure to each four-digit Standard Industrial Classification (SIC) and Standard Occupational Classification (SOC) code potentially associated with exposure to each CAH. The matrix also accounts for the changing patterns of use of the CAHs by decade from the 1920s to the 1980s. An algorithm combines these parameters to assign each study subject a unique lifetime probability of exposure and an estimated score of cumulative exposure for each CAH. These assignments can then become the subjects of analyses. The ability of the matrix to reduce the number of false positive exposure assessments is discussed and illustrated. A companion paper describes the detailed epidemiologic findings of this application of the matrix. (C) 1994 Wiley-Liss, Inc.* C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,OCCUPAT STUDIES SECT,ROCKVILLE,MD. IST MED LAVORO,I-09124 CAGLIARI,ITALY. NR 37 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 1994 VL 26 IS 2 BP 171 EP 183 DI 10.1002/ajim.4700260204 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NY093 UT WOS:A1994NY09300003 PM 7977394 ER PT J AU POWELL, CM TAGGART, RT DRUMHELLER, TC WANGSA, D QIAN, CP NELSON, LM WHITE, BJ AF POWELL, CM TAGGART, RT DRUMHELLER, TC WANGSA, D QIAN, CP NELSON, LM WHITE, BJ TI MOLECULAR AND CYTOGENETIC STUDIES OF AN X-AUTOSOME TRANSLOCATION IN A PATIENT WITH PREMATURE OVARIAN FAILURE AND REVIEW OF THE LITERATURE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE PREMATURE OVARIAN FAILURE; OVARIAN FUNCTION; X CHROMOSOME TRANSLOCATION ID COMPLETE LINKAGE MAP; DINUCLEOTIDE REPEAT; CHROMOSOME RFLP; TURNER SYNDROME; CANDIDATE GENE; SEX-CHROMOSOME; HUMAN FEMALE; LONG-ARM; CHOROIDEREMIA; LOCUS AB We have identified a patient with premature ovarian failure (POF) and a balanced X;autosome translocation: 46,X,t(X;6)(q13.3 or q21;p12) using high-resolution cytogenetic analysis and FISH. BrdU analysis showed that her normal X was late-replicating and translocated X earlier-replicating which is typical of balanced X;autosome rearrangements. Molecular studies were done to characterize the breakpoint on Xq and to determine the parental origin. PCR probes of tetranucleotide and dinucleotide repeat polymorphisms, and genomic probes were used to study DNA from the patient, her chromosomally normal parents and brother, and somatic cell hybrids containing each translocation chromosome. The translocation is paternally derived and is localized to Xq13.3-proximal Xq21.1, between PGK1 and DXS447 loci, a distance of 0.1 centimorgans. A ''critical region'' for normal ovarian function has been proposed for Xq13-q26 [Sarto et al., Am J Hum Genet 25:262-270, 1973; Phelan et al., Am J Obstet Gynecol 129:607-613, 1977; Summitt et al., BD:OAS XIV(6C):219-247, 1978] based on cytogenetic and clinical studies of patients with X;autosome translocations. Few cases have had molecular characterization of the breakpoints to further define the region. While translocations in the region may lead to ovarian dysfunction by disrupting normal meiosis or by a position effect, two recent reports of patients with premature ovarian failure and Xq deletions suggest that there is a gene (POF1) localized to Xq21.3-q27 [Krauss et al., N Engl J Med 317:125-131, 1987; Davies et al., Cytogenet Cell Genet 58:853-966, 1991] or within Xq26.1-q27 [Tharapel et al., Am J Hum Genet 52:463-471, 1993] responsible for POF. We now propose that there may be a second gene for POF (POF2) located at Xq13.3-q21.1. (C) 1994 Wiley-Liss, Inc. C1 NICHHD,INTERINST MED GENET PROGRAM,BETHESDA,MD 20892. NICHHD,CTR CLIN,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIDDK,BIOL CHEM LAB,CYTOGENET UNIT,BETHESDA,MD. WAYNE STATE UNIV,SCH MED,DEPT MOLEC BIOL & GENET,DETROIT,MI 48201. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC. NR 51 TC 111 Z9 119 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 1 PY 1994 VL 52 IS 1 BP 19 EP 26 DI 10.1002/ajmg.1320520105 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA NY099 UT WOS:A1994NY09900004 PM 7977456 ER PT J AU CRANE, JP LEFEVRE, ML WINBORN, RC EVANS, JK EWIGMAN, BG BAIN, RP FRIGOLETTO, FD MCNELLIS, D KANE, D BOYD, L CORNELISON, S PLATTNER, M CRAMER, DW HARLOW, BL TURLINGTON, T BURROWS, PK YAFFE, S CATZ, C QUILLIGAN, EJ HADLOCK, F HOBBINS, JC WILLIAMS, G AF CRANE, JP LEFEVRE, ML WINBORN, RC EVANS, JK EWIGMAN, BG BAIN, RP FRIGOLETTO, FD MCNELLIS, D KANE, D BOYD, L CORNELISON, S PLATTNER, M CRAMER, DW HARLOW, BL TURLINGTON, T BURROWS, PK YAFFE, S CATZ, C QUILLIGAN, EJ HADLOCK, F HOBBINS, JC WILLIAMS, G TI A RANDOMIZED TRIAL OF PRENATAL ULTRASONOGRAPHIC SCREENING - IMPACT ON THE DETECTION, MANAGEMENT, AND OUTCOME OF ANOMALOUS FETUSES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ULTRASONOGRAPHY; FETAL ANOMALIES; RADIUS ID LOW-RISK POPULATION; CONGENITAL-MALFORMATIONS; ULTRASOUND; ABNORMALITIES; PREGNANCY AB OBJECTIVE: The objective of this randomized clinical trial was to test the hypothesis that ultrasonographic screening would significantly alter perinatal outcome as a result of the antenatal detection of fetal congenital malformations. STUDY DESIGN: Pregnant women without a specific indication for ultrasonography were randomly assigned to have either two screening sonograms (15 to 22 weeks and 31 to 35 weeks) or conventional obstetric care with ultrasonography used only as determined by the clinical judgment of the patient's physician. The frequency of birth defect detection in the screened and control populations was compared, as was the impact of discovery on pregnancy outcome. RESULTS: Major congenital malformations occurred in 2.3% of the 15,281 fetuses and infants in this study. Antenatal ultrasonography detected 35% of the anomalous fetuses in the screened group versus only 11% in the control population (relative detection rate 3.1; 95% confidence interval 2.0 to 5.1). Ultrasonography screening did not, however, significantly influence the management or outcome of pregnancies complicated by congenital malformations. Specifically only 9 abortions were performed for anomalies among 7685 fetuses in the screened group whereas 4 pregnancies were terminated for fetal anomalies detected among 7596 control subjects. Ultrasonography screening also had no significant impact on survival rates among infants with potentially treatable, life-threatening anomalies despite the opportunity to take precautionary measures such as delivery in a tertiary center. CONCLUSIONS: Ultrasonography screening in a low-risk pregnant population had no significant impact on the frequency of abortion for fetal anomalies. Survival rates for anomalous fetuses were also unaffected by screening. C1 WASHINGTON UNIV,SCH MED,DEPT OBSTET & GYNECOL,ST LOUIS,MO 63110. UNIV MISSOURI,DEPT FAMILY & COMMUNITY MED,COLUMBIA,MO 65211. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NICHHD,BETHESDA,MD 20892. FU NICHD NIH HHS [HD 21140, HD 19897, HD 21017] NR 16 TC 233 Z9 240 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1994 VL 171 IS 2 BP 392 EP 399 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PC795 UT WOS:A1994PC79500016 PM 8059817 ER PT J AU NEWMAN, NJ TORRONI, A BROWN, MD LOTT, MT FERNANDEZ, MM WALLACE, DC AF NEWMAN, NJ TORRONI, A BROWN, MD LOTT, MT FERNANDEZ, MM WALLACE, DC TI EPIDEMIC NEUROPATHY IN CUBA NOT ASSOCIATED WITH MITOCHONDRIAL-DNA MUTATIONS FOUND IN LEBERS HEREDITARY OPTIC NEUROPATHY PATIENTS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TOBACCO-ALCOHOL AMBLYOPIA; CLINICAL MANIFESTATIONS; COMPLEX-I; CYANIDE; AFFINITIES; DEFICIENCY; PEDIGREES; DISEASES; SEQUENCE; ATROPHY AB An epidemic neuropathy in Cuba has caused bilateral optic neuropathies in more than 26,000 people during the past three years. Various pathogenetic factors have been proposed, including toxins, nutritional deficiencies, and an underlying genetic predisposition involving mitochondrial DNA. As part of a case-control collaborative investigation, 135 Cuban blood samples were analyzed for the most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. None of the participants tested were found to have the mitochondrial DNA mutations at nucleotide positions 11778, 3460, 14484, 7444, or 9804. Of 57 definite case subjects and 69 normal control subjects, three case and three control subjects had the mutation at nucleotide position 9438, three different case and three different control subjects had the mutation at position 13708, and one case and one control subject had the mutation at position 15257 in association with the mutation at position 13708. The most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy do not appear to be contributing factors in the epidemic neuropathy in Cuba. We also identified a large Cuban family with maternally related members who experienced visual loss consistent with the diagnosis of Leber's hereditary optic neuropathy. Maternal family members harbored the highly pathogenetic mutation at nucleotide position 11778. C1 EMORY UNIV,SCH MED,DEPT OPHTHALMOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROSURG,ATLANTA,GA. HOSP AMEIJEIRAS,HAVANA,CUBA. CUBAN MINIST PUBL HLTH,HAVANA,CUBA. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. PAN AMER HLTH ORG,WASHINGTON,DC. PAN AMER HLTH ORG,HAVANA,CUBA. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RP NEWMAN, NJ (reprint author), EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,1462 CLIFTON RD NE,ROOM 403,ATLANTA,GA 30322, USA. RI Torroni, Antonio/E-1557-2011 OI Torroni, Antonio/0000-0002-4163-4478 FU NEI NIH HHS [P30 EY06360]; NINDS NIH HHS [NS21468, NS30164] NR 54 TC 44 Z9 46 U1 1 U2 1 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 AUG PY 1994 VL 118 IS 2 BP 158 EP 168 PG 11 WC Ophthalmology SC Ophthalmology GA PA910 UT WOS:A1994PA91000003 PM 8053461 ER PT J AU CAMPO, E MUNOZ, J MIQUEL, R PALACIN, A CARDESA, A SLOANE, BF EMMERTBUCK, R AF CAMPO, E MUNOZ, J MIQUEL, R PALACIN, A CARDESA, A SLOANE, BF EMMERTBUCK, R TI CATHEPSIN-B EXPRESSION IN COLORECTAL CARCINOMAS CORRELATES WITH TUMOR PROGRESSION AND SHORTENED PATIENT SURVIVAL SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PLASMA-MEMBRANE; IV COLLAGENASE; PROTEINASE; ADENOCARCINOMA; DEGRADATION; UROKINASE; NEOPLASIA; RECEPTOR; TISSUES; CANCER AB Cathepsin B is a lysosomal cysteine proteinase that has the ability, to degrade several extracellular matrix components at both neutral and acidic pH and has been implicated in the progression of several human and rodent tumors. We have studied the expression of cathepsin B in human colorectal tissues using a monospecific polyclonal rabbit antibody raised against human liver cathepsin B. In immunoblots of normal and neoplastic colorectal tissues this antibody specifically recognized only cathepsin B. We studied 101 cases of formalin-fixed, paraffin-embedded tissue (15 normal mucosa, 17 adenomas, and 69 carcinomas). Epithelial cells of normal mucosa and adenomas were either negative or showed a weak granular reactivity located in the paranuclear and apical cytoplasm of superficial cells. Small clusters of histiocytes were also positive in the region of the superficial area of the lamina propria. In carcinomas, increased expression of cathepsin B correlated with advanced stage of the disease. Increased immunoreactivity of cathepsin B in malignant cells was associated with either a diffuse cytoplasmic staining or was polarized to the basal pole of the cells. This is in contrast to the punctate paranuclear staining pattern observed is normal colonic mucosal cells. In tumor stromal cells, increased expression of the enzyme correlated with neoplastic progression. Expression of high levels of cathepsin B in the tumor epithelial cells was associated with a significantly shorter survival of the patients. In conclusion, our results indicate that cathepsin B expression is up-regulated in human colorectal carcinomas compared with normal mucosa and adenomas and correlates with tumor progression. C1 NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BETHESDA,MD 20892. UNIV BARCELONA,HOSP CLIN PROV,ANAT PATHOL LAB,BARCELONA,SPAIN. UNIV LLEIDA,SCH MED,DEPT BASIC MED SCI,LLEIDA,SPAIN. WAYNE STATE UNIV,SCH MED,DEPT PHARMACOL,DETROIT,MI 48201. RI Sloane, Bonnie/A-1050-2009; OI Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [CA 36481] NR 37 TC 179 Z9 181 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1994 VL 145 IS 2 BP 301 EP 309 PG 9 WC Pathology SC Pathology GA PB283 UT WOS:A1994PB28300009 PM 7519824 ER PT J AU WEBBER, EM WU, JC WANG, LQ MERLINO, G FAUSTO, N AF WEBBER, EM WU, JC WANG, LQ MERLINO, G FAUSTO, N TI OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA CAUSES LIVER ENLARGEMENT AND INCREASED HEPATOCYTE PROLIFERATION IN TRANSGENIC MICE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ADULT-RAT HEPATOCYTES; TGF-ALPHA; HEPATOCELLULAR-CARCINOMA; C-MYC; PARTIAL-HEPATECTOMY; EXPRESSION; REGENERATION; DIFFERENTIATION; ONCOGENESIS; PANCREAS AB Transforming growth factor-alpha (TGF-alpha) expression is associated with hepatocyte DNA replication both in vivo and in culture. Our previous work, using TGF-alpha transgenic mice showed that constitutive overexpression of this growth factor in the liver causes hepatic tumors in 75 to 80% of the animals at 12 to 15 months of age. To understand the cellular events by which TGF-alpha overexpression leads to abnormal liver growth, we examined hepatocyte proliferative activity in young and old TGF-alpha transgenic mice and hepatocyte ploidy in normal, dysplastic, and neoplastic fivers of these animals. At 4 weeks of age, transgenic mice had higher liver weights and liver weight/body weight ratios than non-transgenic mice of the same age and hepatocyte proliferative activity, measured by H-3-thymidine incorporation after 3- and 7-day infusion, proliferating cell nuclear antigen staining, and mitotic index determination, was 2 to 3 times higher than in controls. In both transgenic and non-transgenic mice hepatocyte proliferation declined with age but the decrease was much more pronounced in control animals, so that at 8 months of age, hepatocyte replication was 8 to 10 times higher in transgenic animals. Surprisingly, however, transgenic and non-transgenic mice at this age had similar liver weight/body weight ratios. Labeling studies done in 3-month-old animals revealed that hepatocyte turnover was much faster in transgenic than in control animals, suggesting that a homeostatic compensatory mechanism involving cell death tended to restore normal liver weight/body weight ratios in older transgenic mice. Ploidy analyses showed that at 4 weeks of age transgenic mice had a higher proportion of diploid and tetraploid hepatocytes and that the hepatocellular turners which developed in TGF-alpha transgenic mice at 13 months of age contained a higher fraction of diploid hepatocytes than that present in adjacent tissue or in dysplastic livers. The results demonstrate that constitutive overexpression of TGF-alpha causes increased hepatocyte proliferation and fitter enlargement in young animals and is associated with a delay in the establishment of hepatic polyploidy. These findings as well as the response of transgenic mice to partial hepatectomy show that constitutive overexpression of TGF-alpha initially caused increased but regulated hepatocyte proliferation which in older animals was compensated in part by a faster cell turnover At 8 to 10 months of age, proliferative activity may become constitutive in some TGF-alpha expressing hepatocytes. The data also suggest that replicative diploid and tetraploid hepatocytes, rather than large dysplastic cells are the source of the tumors which develop several months later in these animals. C1 BROWN UNIV,SCH MED,DEPT PATHOL & LAB MED,PROVIDENCE,RI 02912. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA23226] NR 41 TC 96 Z9 102 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1994 VL 145 IS 2 BP 398 EP 408 PG 11 WC Pathology SC Pathology GA PB283 UT WOS:A1994PB28300019 PM 8053497 ER PT J AU FACTOR, VM RADAEVA, SA THORGEIRSSON, SS AF FACTOR, VM RADAEVA, SA THORGEIRSSON, SS TI ORIGIN AND FATE OF OVAL CELLS IN DIPIN-INDUCED HEPATOCARCINOGENESIS IN THE MOUSE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RAT-LIVER; STEM-CELL; HEPATOCELLULAR-CARCINOMA; LINEAGE RELATIONSHIPS; ALPHA-FETOPROTEIN; EARLY STAGE; BILE-DUCTS; HEPATOCYTES; CARCINOGENESIS; PROLIFERATION AB We have studied the development and differentiation of oval cells in the Dipin model of hepatocarcinogenesis in the mouse and compared this process to generation of biliary, epithelial cells by bile duct ligation using light and electron microscopy. The Dipin model of hepatocarcinogenesis consists of a single injection of an alkylating drug, Dipin (1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine), followed by partial hepatectomy. The Dipin treatment resulted in irreversible damage and gradual death of hepatocytes by necrosis and apoptosis. Earlier work provided evidence that regeneration of parenchyma occurred via oval cell proliferation and subsequent differentiation into hepatocytes that replaced the degenerating hepatocytes. Both autoradiographic and morphological data indicated that oval cells were derived from ductular cells of Hering canals. The first oval cells labeled with [H-3]thymidine were similar in size and ultrastructure to ductular cells of Hering canals with whom intracellular connections existed. The proliferation of ductular cells of Hering canals gave rise to a new system of oval cell ducts that spread into the liver acinus. In the periportal areas, the transition of oval cells into hepatocytes was observed inside the ducts. Both growth patterns and ultrastructure of oval cells were different from the biliary epithelial cells in bile duct-ligated liver Also, oval cells retained the property to interact with adjacent hepatocytes through desmosomes and intermediate junctions. Oval cell population was heterogeneous in terms of proliferating potential. A proportion of proliferating cells (38 to 45%) in the Hering canals and small oval cell ducts located in the periportal areas was similar throughout the period of oval cell development. The extent of proliferation of oval cells decreased from 62% at the stage of active migration into the acinus to 22% at maximum formation of oval cell ducts. These data suggest that in the mouse fiver cells of the terminal biliary ductules harbor the hepatic stem cell compartment from which oval cells, capable of differentiating into hepatocytes, may be derived. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. AN KOLTSOV INST DEV BIOL,CYTOL LAB,MOSCOW 117334,RUSSIA. NR 52 TC 141 Z9 143 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1994 VL 145 IS 2 BP 409 EP 422 PG 14 WC Pathology SC Pathology GA PB283 UT WOS:A1994PB28300020 PM 8053498 ER PT J AU NAPATHORN, S SPRING, KR AF NAPATHORN, S SPRING, KR TI FURTHER CHARACTERIZATION OF THE SORBITOL PERMEASE IN PAP-HT25 CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CULTURED RABBIT PAPILLARY CELLS; SORBITOL EFFLUX ID PAPILLARY EPITHELIAL-CELLS; VOLUME REGULATION; ALDOSE REDUCTASE; RENAL-CELLS; TRANSPORT; MECHANISM; PROTEIN; SYSTEMS; EFFLUX; NACL AB The sorbitol permease enables the efflux of sorbitol from cultured rabbit papillary cells (PAP-HT25) in response to a reduction in osmolality. The anion transport inhibitor 5-nitro-2-(3-phenylpropylamino)benzoate (100 mu M) inhibited efflux by 92%, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.5 mN) reduced efflux by 40%. 2,4-DinitrobenzenesuIfonate and p-chloromercuriphenylsulfonic acid had no effect. The protease trypsin (0.05 mg/ml) reduced sorbitol efflux by 53%, pronase (0.01 mg/ml) by 47%, and papain (0.1 mg/ml) by 49%; chymotrypsin had no effect. Sugars and sugar alcohols at different concentrations (10-200 mM) in the bathing solution did not influence sorbitol efflux. Determination of the osmotically induced influx of sugar alcohols showed that xylitol uptake was faster than that of sorbitol; 6-deoxysorbitol was slower; L-sorbitol, arabitol, galactitol, and 2-deoxysorbitol entered at the same rate as sorbitol; and maltitol did not enter the cells. Sorbitol and 6-deoxysorbitol at 9 mM competitively inhibited [C-14]sorbitol influx by 24 and 32%, respectively, whereas xylitol, taurine, betaine, and myo-inositol showed no inhibition. We conclude that 1) a specific inhibitor of the permease was not found, 2) the sorbitol permease or associated regulator is a protein, and 3) the C-6 atom of sorbitol is important in the selectivity of the permease. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 23 TC 14 Z9 14 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 AUG PY 1994 VL 267 IS 2 BP C514 EP C519 PN 1 PG 6 WC Physiology SC Physiology GA PC439 UT WOS:A1994PC43900022 PM 8074186 ER PT J AU BIKLE, DD HARRIS, J HALLORAN, BP ROBERTS, CT LEROITH, D MOREYHOLTON, E AF BIKLE, DD HARRIS, J HALLORAN, BP ROBERTS, CT LEROITH, D MOREYHOLTON, E TI EXPRESSION OF THE GENES FOR INSULIN-LIKE GROWTH-FACTORS AND THEIR RECEPTORS IN BONE DURING SKELETAL GROWTH SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE DEVELOPMENT; AGE; FETUS; TIBIA; POSTNATAL ID I IGF-I; MESSENGER-RIBONUCLEIC-ACID; OSTEOBLAST-ENRICHED CULTURES; FETAL-RAT BONE; PARATHYROID-HORMONE; SOMATOMEDIN-C; DEVELOPMENTAL EXPRESSION; TISSUES; INVIVO; LIVER AB Insulin-like growth factors (IGF) are important regulators of skeletal growth. To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. The mRNA levels remained high during fetal development but fell after birth, reaching a nadir by 3-6 wk. This fall was most pronounced for IGF-II and IGF-IIR mRNA,4 and least pronounced for IGF-I mRNA. However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. We conclude that, during development, rat bone changes its capacity to produce and respond to IGFs with a progressive trend toward the dominance of IGF-I. C1 NIH,DIABET BRANCH,BETHESDA,MD 20892. NASA,AMES RES CTR,MOFFETT FIELD,CA 94035. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94121. NR 29 TC 10 Z9 10 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 AUG PY 1994 VL 267 IS 2 BP E278 EP E286 PN 1 PG 9 WC Physiology SC Physiology GA PC439 UT WOS:A1994PC43900050 PM 8074208 ER PT J AU BURSON, JM AGUILERA, G GROSS, KW SIGMUND, CD AF BURSON, JM AGUILERA, G GROSS, KW SIGMUND, CD TI DIFFERENTIAL EXPRESSION OF ANGIOTENSIN RECEPTOR 1A AND 1B IN MOUSE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE; RENIN-ANGIOTENSIN SYSTEM ID VASCULAR SMOOTH-MUSCLE; II TYPE-1 RECEPTOR; TRANSGENIC MICE; GENE-EXPRESSION; MESSENGER-RNA; RAT; RENIN; CELLS; CLONING; LOCALIZATION AB At least two distinct genes (AT(1A) and AT(1B)) encode type 1 angiotensin II (AT(1)) receptors in rodents. Receptor binding and Northern blot analysis have clearly demonstrated the presence of AT(1) receptors and AT(1)-receptor mRNA in many tissues but fail to differentiate which type 1 receptor subtype is expressed. A reverse-transcriptase polymerase chain reaction restriction fragment length polymorphism (RT-PCR-RFLP) assay was developed to differentiate the expressed mRNA by subtype. Expression of AT(1A) was clearly evident in kidney, liver, adrenal gland, ovary, brain, testes, adipose tissue, lung, and heart of adult mice. AT(1B) was absent from most of these tissues but was detectable in brain, testes, and adrenal gland. No significant differences in expression were evident in kidney, liver, brain, lung, or heart from 16.5- or 18.5-gestation-day fetuses, and only AT(1A) was evident in placenta. Expression of AT(1B) was confirmed in adrenal gland, brain, and testes, using a primer set that specifically amplifies only AT(1B) mRNA. Expression of AT(1A) and AT(1B) was also examined in As4.1 cells, a renin-expressing mouse kidney tumoral cell line. Receptor binding and competition assays using AT(1)- and AT(2)-receptor antagonists revealed that only AT(1) receptors are present on the cell surface. Extremely low levels of AT(1)-receptor mRNA was detected by Northern blot, and RT-PCR-RFLP analysis revealed that only the AT(1A) subtype is expressed in this cell line. Despite the high homology between the coding sequence of the AT(1A) and AT(1B) genes, they exhibit disparate tissue-specific expression profiles. C1 UNIV IOWA,COLL MED,DEPT MED,IOWA CITY,IA 52242. NICHHD,BETHESDA,MD 20592. ROSWELL PK CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14263. UNIV IOWA,COLL MED,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242. FU NHLBI NIH HHS [HL-48459, HL-48058] NR 38 TC 166 Z9 171 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 AUG PY 1994 VL 267 IS 2 BP E260 EP E267 PN 1 PG 8 WC Physiology SC Physiology GA PC439 UT WOS:A1994PC43900047 PM 8074205 ER PT J AU JOANNIDIS, M SPOKES, K NAKAMURA, T FALETTO, D CANTLEY, LG AF JOANNIDIS, M SPOKES, K NAKAMURA, T FALETTO, D CANTLEY, LG TI REGIONAL EXPRESSION OF HEPATOCYTE GROWTH-FACTOR C-MET IN EXPERIMENTAL RENAL HYPERTROPHY AND HYPERPLASIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE KIDNEY; ISCHEMIA; UNINEPHRECTOMY ID FACTOR MESSENGER-RNA; EPITHELIAL-CELLS; UNILATERAL NEPHRECTOMY; RAT-KIDNEY; INJURY; REGENERATION; GENE; IDENTIFICATION; NA,K-ATPASE; MECHANISMS AB Hepatocyte growth factor (HGF) and its high-affinity receptor, c-met, have been found to increase in the whole kidney of the rat following several types of renal injury or renal hypertrophy. In an attempt to determine whether the upregulation of this growth factor and its receptor is selective for the regions of greatest anatomic change, and therefore likely to be important in regulating renal tubular hyperplasia and/or hypertrophy, we examined their expression in liver, whole kidney, and subsections of the kidney following either sham operation, transient ischemia of one kidney, or unilateral nephrectomy. The message for HGF was increased in both liver and kidney by all surgical procedures tested, including sham operation, and was seen predominantly in the outer cortex, the site of least morphological change. However, c-met was not upregulated by sham operation or in the liver, but rather was selectively upregulated only in the kidney in both the hypertrophy and hyperplasia (ischemia/reflow) models. Renal subsections revealed that this increase was confined to the renal medulla, with the greatest change in the outer medulla. Thus induction of the message for HGF can occur nonselectively and at sites distant to the injurious stimulus, whereas the target for HGF, c-met, is upregulated selectively at the site of greatest tubular injury or hypertrophy. These results support a role for HGF/c-met in regulation of these renal tubular events. C1 NCI,FREDERICK,MD 21702. KYUSHU UNIV,DEPT BIOL,FUKUOKA 812,JAPAN. RP JOANNIDIS, M (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV RENAL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-18078] NR 24 TC 58 Z9 59 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 AUG PY 1994 VL 267 IS 2 BP F231 EP F236 PN 2 PG 6 WC Physiology SC Physiology GA PC441 UT WOS:A1994PC44100096 PM 8067383 ER PT J AU VENTURA, C FERRONI, C FLAMIGNI, F STEFANELLI, C CAPOGROSSI, MC AF VENTURA, C FERRONI, C FLAMIGNI, F STEFANELLI, C CAPOGROSSI, MC TI POLYAMINE EFFECTS ON [CA2+](I) HOMEOSTASIS AND CONTRACTILITY IN ISOLATED RAT VENTRICULAR CARDIOMYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE INDO 1; CYTOSOLIC CALCIUM; BETA-ADRENERGIC STIMULATION; ORNITHINE DECARBOXYLASE; ALPHA-DIFLUOROMETHYLORNITHINE ID ORNITHINE DECARBOXYLASE ACTIVITY; MEMBRANE-TRANSPORT; CARDIAC MYOCYTES; CELLS; HEART; SPERMINE; CURRENTS; RELEASE; MUSCLE; WAVES AB In electrically stimulated myocytes loaded with the fluorescent Ca2+ indicator indo 1-acetoxymethyl ester, spermine induced a dose-dependent (100-500 mu M) negative inotropic effect, which was associated with a decrease in the magnitude of the cytosolic Ca2+ concentration ([Ca2+](i)) transient but not with changes in myofilament responsiveness to Ca2+. Spermidine induced a less pronounced negative inotropic effect, whereas putrescine did not modify myocyte contraction. In the unstimulated state, spermine did not alter resting [Ca2+](i). Superfusion of the cardiac myocytes with 10 mM alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, did not modify cellular responses to isoproterenol (10(-9)-10(-7)M). beta-Adrenergic stimulation did not affect either ornithine decarboxylase activity or intracellular polyamine levels within a 10-s to 15-min period of treatment. In summary, only exogenously administered polyamines were able to influence myocyte contractility. Their negative inotropic effect resulted from changes in [Ca2+](i) homeostasis and required cellular depolarization. C1 ITALIAN NATL RES CTR AGING,EXPTL CARDIOL LAB,I-60100 ANCONA,ITALY. UNIV BOLOGNA,DEPT BIOCHEM G MORUZZI,I-40126 BOLOGNA,ITALY. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP VENTURA, C (reprint author), UNIV SASSARI,SCH MED,INST BIOL CHEM A BONSIGNORE,VIALE SAN PIETRO 43-B,I-07100 SASSARI,ITALY. NR 29 TC 24 Z9 24 U1 0 U2 2 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 AUG PY 1994 VL 267 IS 2 BP H587 EP H592 PN 2 PG 6 WC Physiology SC Physiology GA PC441 UT WOS:A1994PC44100025 PM 8067415 ER PT J AU CANTORGRAAE, E MCNEIL, TF TORREY, EF QUINN, P BOWLER, A SJOSTROM, K RAWLINGS, R AF CANTORGRAAE, E MCNEIL, TF TORREY, EF QUINN, P BOWLER, A SJOSTROM, K RAWLINGS, R TI LINK BETWEEN PREGNANCY COMPLICATIONS AND MINOR PHYSICAL ANOMALIES IN MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSTETRIC COMPLICATIONS; PRENATAL EXPOSURE; MEDICAL RECORDS; CHILDREN; MALFORMATIONS; RECALL AB Objective: The aim of the current study was to explore the relevancy of early pregnancy complications for the development of minor physical anomalies in monozygotic twins discordant and concordant for schizophrenia. Method: Pregnancy complications and minor physical anomalies were independently assessed in 22 discordant, 10 concordant, and six normal comparison monozygotic twin pairs. Results: Complications occurring during early pregnancy were associated with a higher frequency of minor physical anomalies in the total group and in the discordant twin pairs particularly. While no significant differences ill anomaly rates were observed among the discordant, concordant, and normal comparison groups, the discordant ill twins showed a trend toward having more anomalies than their well co-twins. Conclusions: Complications occurring early in pregnancy are relevant for the development of minor physical anomalies and may be of particular importance for the development of these anomalies in twin pairs discordant for schizophrenia. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. RP CANTORGRAAE, E (reprint author), LUND UNIV,MALMO GEN HOSP,DEPT PSYCHIAT,S-21401 MALMO,SWEDEN. FU NIMH NIH HHS [NIMH MH-41176] NR 37 TC 38 Z9 38 U1 1 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1994 VL 151 IS 8 BP 1188 EP 1193 PG 6 WC Psychiatry SC Psychiatry GA NZ334 UT WOS:A1994NZ33400015 PM 8037254 ER PT J AU CANTORGRAAE, E MCNEIL, TF RICKLER, KC SJOSTROM, K RAWLINGS, R HIGGINS, ES HYDE, TM AF CANTORGRAAE, E MCNEIL, TF RICKLER, KC SJOSTROM, K RAWLINGS, R HIGGINS, ES HYDE, TM TI ARE NEUROLOGICAL ABNORMALITIES IN WELL DISCORDANT MONOZYGOTIC CO-TWINS OF SCHIZOPHRENIC SUBJECTS THE RESULT OF PERINATAL TRAUMA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SOFT SIGNS; OBSTETRIC COMPLICATIONS; CHILDREN; RISK AB Objective: Neurological abnormalities found in schizophrenic subjects and their healthy relatives have raised questions concerning etiology. The aim of the present study was to investigate the genetic and environmental antecedents of neurological impairment in monozygotic twins discordant for schizophrenia, with particular focus on the well discordant twins. The etiological factors of interest were history of obstetric complications, family history of psychosis, history of substance abuse, and history of postnatal cerebral trauma. Method: History of obstetric complications, including information from pregnancy through the neonatal period, and data on neurological ''hard'' and ''soft'' signs were obtained blindly and separately for each member of 22 monozygotic twin pairs discordant for schizophrenia and seven normal comparison monozygotic twin pairs. Clinical and family interviews provided information about background factors. Results: Degree of neurological impairment in the well discordant monozygotic twins was significantly positively related to history of both neonatal and total obstetric complications. None of the three other background factors investigated was related to degree of neurological impairment in the ill or well co-twins. Conclusions: The contribution of obstetric complications to the current level of neurological impairment in well discordant co-twins suggests that the spectrum of neuroabnormality, ranging from neurological signs to schizophrenia, in monozygotic discordant twins may be the result of subtle gene-environment interaction. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. RP CANTORGRAAE, E (reprint author), LUND UNIV,MALMO GEN HOSP,DEPT PSYCHIAT,S-21401 MALMO,SWEDEN. FU NIMH NIH HHS [NIMH MH-41176] NR 36 TC 50 Z9 50 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1994 VL 151 IS 8 BP 1194 EP 1199 PG 6 WC Psychiatry SC Psychiatry GA NZ334 UT WOS:A1994NZ33400016 PM 8037255 ER PT J AU CANTOR, KP AF CANTOR, KP TI WATER CHLORINATION, MUTAGENICITY, AND CANCER-EPIDEMIOLOGY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID POTENT BACTERIAL MUTAGEN; DRINKING-WATER; 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE RP CANTOR, KP (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 14 TC 22 Z9 24 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1994 VL 84 IS 8 BP 1211 EP 1213 DI 10.2105/AJPH.84.8.1211 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC266 UT WOS:A1994PC26600001 PM 8059872 ER PT J AU RILEY, MW AF RILEY, MW TI CHANGING LIVES AND CHANGING SOCIAL-STRUCTURES - COMMON CONCERNS OF SOCIAL-SCIENCE AND PUBLIC-HEALTH SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material RP RILEY, MW (reprint author), NIA,7201 WISCONSIN AVE,GATEWAY BLDG,525A,BETHESDA,MD 20892, USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1994 VL 84 IS 8 BP 1214 EP 1217 DI 10.2105/AJPH.84.8.1214 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC266 UT WOS:A1994PC26600003 PM 8059874 ER PT J AU WARREN, JL BACON, WE HARRIS, T MCBEAN, AM FOLEY, DJ PHILLIPS, C AF WARREN, JL BACON, WE HARRIS, T MCBEAN, AM FOLEY, DJ PHILLIPS, C TI THE BURDEN AND OUTCOMES ASSOCIATED WITH DEHYDRATION AMONG US ELDERLY, 1991 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PROTECTIVE EFFICACY; VACCINE; RISK AB Objectives, De-hydration has been underappreciated as a cause of hospitalization and increased hospital-associated mortality in older people. This study used national data to analyze the burden and outcomes following hospitalizations with dehydration in the elderly. Methods. Data from 1991 Medicare files were used to calculate rates of hospitalization with dehydration, to examine demographic characteristics and concomitant diagnoses associated with dehydration, and to analyze the contribution of dehydration to mortality. Results. In 1991, 6.7% (731695) of Medicare hospitalizations had dehydration listed as one of the five reported diagnoses, a rate of 236.2/10000 elderly Medicare beneficiaries. In 1991, Medicare reimbursed over $446 million for hospitalizations with dehydration as the principal diagnosis. Older people, men, and Blacks had elevated risks for hospitalization with dehydration, Acute infections, such as pneumonia and urinary tract infections, were frequent concomitant diagnoses. About 50% of elderly Medicare beneficiaries hospitalized with dehydration died within a year of admission. Conclusions, Hospitalization of elderly people with dehydration is a serious and costly medical problem. Attention should be focused on understanding predisposing factors and devising strategies for prevention. C1 CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRM,BETHESDA,MD 20892. RP WARREN, JL (reprint author), HLTH CARE FINANCING ADM,RES OFF,EPIDEMIOL BRANCH,2504 OAK MEADOWS BLDG,6325 SECUR BLVD,BALTIMORE,MD 21207, USA. NR 20 TC 100 Z9 100 U1 0 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1994 VL 84 IS 8 BP 1265 EP 1269 DI 10.2105/AJPH.84.8.1265 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC266 UT WOS:A1994PC26600012 PM 8059883 ER PT J AU DWYER, JT MADANS, JH TURNBULL, B CORNONIHUNTLEY, J DRESSER, C EVERETT, DF PERRONE, RD AF DWYER, JT MADANS, JH TURNBULL, B CORNONIHUNTLEY, J DRESSER, C EVERETT, DF PERRONE, RD TI DIET, INDICATORS OF KIDNEY-DISEASE, AND LATER MORTALITY AMONG OLDER PERSONS IN THE NHANES-I EPIDEMIOLOGIC FOLLOW-UP-STUDY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RENAL-INSUFFICIENCY; PROTEIN RESTRICTION; PROGRESSION AB Objectives. The purpose of this study was to determine whether diet adversely affected survival among 2572 older persons with indicators of kidney disease in a population-based cohort. Average follow-up time for survivors, of whom 1453 (57%) had died at analysis, was 14.5 years. Methods. Kidney disease indicators were a ''yes'' response to ''Has a doctor ever told you that you have kidney disease or renal stones?'' and/or trace or greater amounts of protein in urine. Dietary protein intakes were calculated from 24-hour recalls. Results. Cox proportional hazards models were used, stratified by sex, with age, body mass index, blood pressure, education, smoking status, total caloric intake, and diabetes mellitus as covariates. Relative risk of total mortality with an additional 15 g of protein per day was 1.25 (95% confidence interval [CI] = 1.09, 1.42) among White men with kidney disease indicators, vs 1.00 (95% CI = 0.95, 1.06) among those without them; relative risks of renal-related mortality were 1.32 (95% CI = 0.97, 1.79) and 0.95 (95% CI = 0.81, 1.11), respectively. No significant differences were found for White women. Conclusions, Once chronic renal disease is present, diet may be associated with earlier mortality in White males. C1 TUFTS UNIV,SCH MED,BOSTON,MA 02111. TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. NATL CTR HLTH STAT,DIV ANAL,HYATTSVILLE,MD 20782. NIA,BETHESDA,MD 20892. NCI,PUBL HLTH APPL RES BRANCH,ROCKVILLE,MD. NEI,COLLABORAT CLIN RES BRANCH,BETHESDA,MD 20892. RP DWYER, JT (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR HOSP,FRANCES STERN NUTR CTR,DIV NEPHROL,BOX 783,750 WASHINGTON ST,BOSTON,MA 02111, USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 36 TC 8 Z9 9 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1994 VL 84 IS 8 BP 1299 EP 1303 DI 10.2105/AJPH.84.8.1299 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PC266 UT WOS:A1994PC26600018 PM 8059889 ER PT J AU FIDEL, PL ROMERO, R RAMIREZ, M CUTRIGHT, J EDWIN, SS LAMARCHE, S COTTON, DB MITCHELL, MD AF FIDEL, PL ROMERO, R RAMIREZ, M CUTRIGHT, J EDWIN, SS LAMARCHE, S COTTON, DB MITCHELL, MD TI INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL-1RA) PRODUCTION BY HUMAN AMNION, CHORION, AND DECIDUA SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE IL-1 RECEPTOR ANTAGONIST; INTRAUTERINE TISSUE; CYTOKINE; ENDOTOXIN; PRETERM LABOR ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; PRETERM PARTURITION; FACTOR-ALPHA; PROSTAGLANDIN BIOSYNTHESIS; PRIMARY CULTURE; CELLS; LABOR; INFECTION; EXPRESSION AB PROBLEM: This study was conducted to determine whether (1) conditioned media from unstimulated primary cultures of human amnion, chorion, or decidua contain detectable concentrations of IL-1ra in vitro, and (2) bacterial endotoxin (LPS), tumor necrosis factor-alpha ( TNF-alpha), or IL-1-beta (IL-1beta) stimulate amnion, chorion, or decidua to produce increased amounts of IL-1ra. METHOD: Placentae were obtained from women at term with intact membranes before the onset of labor. Amnion, chorion, and decidual cells were isolated by standard procedures and grown to confluence. Cells were then cultured in quadruplicate for 16 h in tissue culture medium supplemented with 10% fetal calf serum or, additionally, with various concentrations of Eschrichia coli LPS, TNF-alpha, or IL-1beta. Culture supernatants were collected, and concentrations of IL-1ra were quantitated by a sensitive and specific enzyme-linked immunosorbent assay for IL-1ra. RESULTS: Results showed that primary cultures of amnion and chorion from 4 of 9 and decidua from 10 of 12 placentae had detectable rates of production of IL-1ra (ranges: 0.08-6.5, 0.42-12.1, and 1.55-96.5 pg IL-1ra/mug protein/16 h, respectively). In addition, LPS (10-1,000 ng/ml) and IL-1beta (0.1-10 ng/ml), but not TNF-alpha (0.01-100 ng/ml), stimulated decidual cells to release/secrete increased amounts of IL-1ra compared with media alone (range: 2.5-400 pg IL-1ra/pg protein/16 h, P < 0.0001). In contrast, neither LPS, TNF-alpha, or IL-1beta could stimulate amnion or chorion to release/secrete IL-1ra. CONCLUSIONS: These results indicate (1) that amnion, chorion, and predominantly decidua, can release or secrete IL-1ra in vitro, and (2) that LPS and IL-1beta can stimulate decidual cells to produce increased amounts of IL-1ra. C1 NICHHD,PERINATOL BRANCH,BETHESDA,MD. WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. UNIV UTAH,DEPT OBSTET & GYNECOL,SALT LAKE CITY,UT 84112. RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 NR 27 TC 41 Z9 41 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD AUG PY 1994 VL 32 IS 1 BP 1 EP 7 PG 7 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA NX982 UT WOS:A1994NX98200001 PM 7945810 ER PT J AU SAUNDERS, NA SMITH, RJ JETTEN, AM AF SAUNDERS, NA SMITH, RJ JETTEN, AM TI DIFFERENTIAL RESPONSIVENESS OF HUMAN BRONCHIAL EPITHELIAL-CELLS, LUNG-CARCINOMA CELLS, AND BRONCHIAL FIBROBLASTS TO INTERFERON-GAMMA IN-VITRO SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID BINDING PROTEIN; ALPHA-INTERFERON; IFN-GAMMA; T-CELLS; MACROPHAGES; EXPRESSION; TRANSCRIPTION; GENE; TRANSGLUTAMINASE; KERATINOCYTES AB The present study examines interferon-gamma (IFN gamma)-induced changes in the expression of immunomodulatory genes, proliferation-associated genes, and squamous-specific genes in primary cultures of human bronchial epithelial cells and fibroblasts. IFN gamma induced the expression of guanylate binding protein (GBP or p67) and the MHC class II antigen, HLADR alpha, in both epithelial cells and fibroblasts. In contrast, the expression of complement component C3 was induced in bronchial epithelial cells but not in fibroblasts. Similarly, IFN gamma induced growth arrest (EC(50) approximately 50 U/ml) only in bronchial epithelial cells. This growth arrest was accompanied by a down-regulation of cdc2, E2F-1, and p53 mRNA levels and was associated with expression of the squamous-specific marker genes, transglutaminase type I and cornifin. These findings are consistent with IFN gamma inducing squamous differentiation in bronchial epithelial cells. In contrast, several lung carcinoma cell lines did not respond to IFN gamma with respect to the downregulation of proliferation-associated genes or the induction of squamous-specific genes. However, GBP expression was induced in all the cell lines in response to IFN gamma. The present study demonstrates that cultured human bronchial epithelial cells are sensitive to the immunomodulatory, growth-inhibitory, and differentiation-inducing properties of IFN gamma. In contrast, several lung carcinoma cell lines are insensitive to the growth-inhibitory and differentiation-inducing actions of IFN gamma, suggesting they may have acquired defects in certain IFN gamma signaling pathways. Although the growth of human bronchial fibroblasts is not altered, expression of certain immunomodulatory genes is induced by IFN gamma. Our data support the hypothesis that both human bronchial epithelial cells and fibroblasts are important targets of IFN gamma action in vivo. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 31 TC 41 Z9 41 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1994 VL 11 IS 2 BP 147 EP 152 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PC052 UT WOS:A1994PC05200004 PM 8049075 ER PT J AU FELLEYBOSCO, E AMBS, S LOWENSTEIN, CJ KEEFER, LK HARRIS, CC AF FELLEYBOSCO, E AMBS, S LOWENSTEIN, CJ KEEFER, LK HARRIS, CC TI CONSTITUTIVE EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN HUMAN BRONCHIAL EPITHELIAL-CELLS INDUCES C-FOS AND STIMULATES THE CGMP PATHWAY SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID INTERFERON-GAMMA; MURINE MACROPHAGES; RAT LUNG; INHIBITION; MECHANISM; RELEASE; DIFFERENTIATION; ACTIVATION; MODULATION; CYTOKINES AB Two major roles have been defined for nitric oxide (NO): cell-cell communication mediated by the stimulation of cyclic guanosine 3',5'-monophosphate (cGMP) synthesis and cytotoxicity by direct or indirect interaction of the free radical NO with cellular targets. Thus, pathologic states might result from an alteration of NO pathways, e.g., by deregulated activity of NO synthase. To investigate this hypothesis, we introduced the murine-inducible NO synthase (iNOS) sequence into immortalized human bronchial epithelial cells (BEAS-2B). iNOS activity, measured by conversion of [C-14]arginine to [C-14]citrulline in the presence of 1 mM EGTA, was higher than 100 pmol/min/mg protein in early passages of iNOS-transfected cells but decreased with cell subculturing. No iNOS activity could be detected in control vector-transfected cells. NO stimulated cGMP production in iNOS-transfected cells, and this effect was inhibited by the iNOS inhibitor N-G-monomethyl-L-arginine. In addition, NO production induced c-fos expression and did not interfere with clonal cell growth. These results suggest that BEAS-2B cells constitute a suitable model to study the consequences of iNOS activity on signal transduction pathways in bronchial epithelium. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD. RI Keefer, Larry/N-3247-2014; Felley-Bosco, Emanuela/E-7484-2017 OI Keefer, Larry/0000-0001-7489-9555; Felley-Bosco, Emanuela/0000-0002-3408-0294 NR 35 TC 44 Z9 45 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1994 VL 11 IS 2 BP 159 EP 164 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PC052 UT WOS:A1994PC05200006 PM 7519434 ER PT J AU OHKUBO, K LEE, CH BARANIUK, JN MERIDA, M HAUSFELD, JN KALINER, MA AF OHKUBO, K LEE, CH BARANIUK, JN MERIDA, M HAUSFELD, JN KALINER, MA TI ANGIOTENSIN-CONVERTING ENZYME IN THE HUMAN NASAL-MUCOSA SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID PATHO-PHYSIOLOGY; KININASE-II; SECRETIONS; RHINITIS; HYDROLYSIS; BRADYKININ; PROTEIN; SERUM; INVIVO AB Angiotensin-converting enzyme (ACE; EC 3.4.15.1) may participate in respiratory inflammatory diseases by regulating levels of inflammatory peptides such as bradykinin. The presence of ACE in the human nasal mucosa and in nasal secretions was determined by immunohistochemistry, measures of enzyme activity, and immunoblot. ACE activity was significantly more abundant in the membrane-rich fraction than in the soluble cytosolic fraction of nasal mucosal extracts (74.18 +/- 24.50 versus 3.99 +/- 1.83 pmol/min/mg protein, respectively, P < 0.01 by an enkephalin degradation assay; 89.16 +/- 16.17 versus 2.30 +/- 0.89 mU/mg protein, P < 0.01 by colorimetric assessment of Bz-Gly-Gly-Gly degradation). Topical application of histamine stimulated secretion of ACE activity into nasal lavage fluid (2.90 +/- 0.88 versus 1.53 +/- 0.45 U/liter after saline provocation, P < 0.05 by Bz-Gly-Gly-Gly assay). Allergen challenge also induced nasal secretion of ACE. In both histamine and allergen challenges, ACE release correlated closely with that of the vascular proteins IgG and albumin. Methacholine, a stimulant of glandular secretions, failed to augment ACE levels above baseline. ACE-immunoreactive material was localized by the immunogold technique with silver enhancement to the glycocalyx, between epithelial cells, and to interstitial, extracellular sites in the superficial lamina propria, with the highest intensity of staining immediately beneath the basement membrane. Some ACE was detectable in the mucus material of gland and duct lumens but not in gland cells themselves. Endothelial cells and some interstitial mononuclear cells also stained for ACE. ACE was identified by immunoblotting as a 150 kD band on SDS-PAGE. Membrane fractions contained more immunoreactive material than cytosolic fractions. These data suggest that ACE originates from plasma and possibly endothelial or mononuclear cell membranes and that plasma-derived ACE enters nasal secretions by extravasation from vessels in the superficial lamina propria, followed by exudation through the interstitial space and between epithelial cells to reach the nasal epithelial lining fluid. ACE in the interstitial or epithelial lining fluids may regulate the actions of peptides such as bradykinin, substance P, or other substrates in vivo. C1 GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,DIV RHEUMATOL IMMUNOL & ALLERGY,WASHINGTON,DC 20007. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. WASHINGTON HOSP CTR,DEPT FACIAL PLAST & RECONSTRUCT SURG,WASHINGTON,DC 20010. WASHINGTON HOSP CTR,INST ASTHMA & ALLERGY,WASHINGTON,DC 20010. NR 36 TC 6 Z9 6 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1994 VL 11 IS 2 BP 173 EP 180 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PC052 UT WOS:A1994PC05200008 PM 8049077 ER PT J AU LARIVEE, P LEVINE, SJ MARTINEZ, A WU, T LOGUN, C SHELHAMER, JH AF LARIVEE, P LEVINE, SJ MARTINEZ, A WU, T LOGUN, C SHELHAMER, JH TI PLATELET-ACTIVATING-FACTOR INDUCES AIRWAY MUCIN RELEASE VIA ACTIVATION OF PROTEIN-KINASE-C - EVIDENCE FOR TRANSLOCATION OF PROTEIN-KINASE-C TO MEMBRANES SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID RESPIRATORY GLYCOCONJUGATE RELEASE; FACTOR STIMULATES SECRETION; BRONCHIAL EPITHELIAL-CELLS; DEPENDENT MECHANISM; HUMAN-NEUTROPHILS; RAT-BRAIN; EXPRESSION; PURIFICATION; POTENT; ALPHA AB Platelet-activating factor (PAF), a proinflammatory lipid mediator, is a potent airway mucin secretagogue. This study assessed the role of protein kinase C (PKC) in PAF-induced mucin release from primary cultures of feline tracheal epithelial cells (FTEC). Mucin secretion was quantitated by enzyme-linked immunosorbent assay using a monoclonal antibody raised against airway mucin-type glycoproteins. Coincubation of FTEC with PAF (5 mu M) and pharmacologic PKC inhibitors, sphingosine, H7, or calphostin C, inhibited PAF-induced mucin secretion at 30 min. The PKC inhibitors produced a concentration-dependent, noncytotoxic inhibition. Exposure of FTEC with the PKC activator phorbol 12-myristate 13-acetate (PMA), failed to increase the release of mucin. Stimulation of FTEC with PAF caused a transient increase of membrane-bound PKC activity after 5 min of stimulation. PMA also induced the translocation of PKC activity from the cytosol to the membrane fraction, which was still present after 15 min of exposure. Determination of the specific PKC isozyme(s) involved in PAF-induced mucin release was performed by immunoblot analysis of the subcellular fractions using a battery of antibodies against various PKC isozymes (anti-PKC alpha, beta, delta, gamma, epsilon, and zeta). We found that PKC zeta (mol wt approximate to 70 kD) was a major identifiable PKC isozyme present in the cytosolic fraction of FTEC. Furthermore, PKC zeta isozyme was also found to translocate to the membrane fraction following PAF exposure. Thus, these results demonstrate the crucial role of PKC in the intracellular events that culminate in mucin release following PAF stimulation. However, our data indicate that although PKC appears to be involved in signaling pathways regulating airway mucin secretion, isolated PKC activation alone is insufficient for mucin exocytosis. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 45 TC 41 Z9 41 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1994 VL 11 IS 2 BP 199 EP 205 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PC052 UT WOS:A1994PC05200011 PM 8049080 ER PT J AU GIERKE, CL KING, BF BOSTWICK, DG CHOYKE, PL HATTERY, RR AF GIERKE, CL KING, BF BOSTWICK, DG CHOYKE, PL HATTERY, RR TI LARGE-CELL CALCIFYING SERTOLI-CELL TUMOR OF THE TESTIS - APPEARANCE AT SONOGRAPHY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID MASSES C1 MAYO CLIN & MAYO FDN,DEPT DIAGNOST RADIOL,ROCHESTER,MN 55905. UNIV N DAKOTA,SCH MED,MANDAN,ND 58554. MAYO CLIN & MAYO FDN,DEPT LAB MED & PATHOL,ROCHESTER,MN 55905. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 8 TC 22 Z9 24 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1994 VL 163 IS 2 BP 373 EP 375 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE289 UT WOS:A1994QE28900029 PM 8037034 ER PT J AU GUINEE, D JAFFE, E KINGMA, D FISHBACK, N WALLBERG, K KRISHNAN, J FRIZZERA, G TRAVIS, W KOSS, M AF GUINEE, D JAFFE, E KINGMA, D FISHBACK, N WALLBERG, K KRISHNAN, J FRIZZERA, G TRAVIS, W KOSS, M TI PULMONARY LYMPHOMATOID GRANULOMATOSIS - EVIDENCE FOR A PROLIFERATION OF EPSTEIN-BARR-VIRUS INFECTED B-LYMPHOCYTES WITH A PROMINENT T-CELL COMPONENT AND VASCULITIS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LYMPHOMATOID GRANULOMATOSIS; ANGIOCENTRIC IMMUNOPROLIFERATIVE LESION; EPSTEIN-BARR VIRUS; B-CELL LINEAGE; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE ID ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; POLYMERASE CHAIN-REACTION; CENTRAL NERVOUS-SYSTEM; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LYMPHADENOPATHY-LIKE LYMPHOMA; RENAL-TRANSPLANT RECIPIENT; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; MALIGNANT-LYMPHOMA; GENE REARRANGEMENT AB Similarities have been noted in the histologic patterns of lymphomatoid granulomatosis and Epstein-Barr virus associated lymphoproliferative disease involving the lung. Epstein-Barr virus has also been identified by polymerase chain reaction in most cases of lymphomatoid granulomatosis; however, the precise cellular localization of Epstein-Parr virus sequences has not been extensively studied. We analyzed 10 cases of lymphomatoid granulomatosis involving the lung by immunohistochemistry and combined immunohistochemistry with in situ hybridization for Epstein-Barr virus, CD20, and CD45RO. All cases were selected from the files of the Armed Forces Institute of Pathology and met the clinical and histologic criteria for the diagnosis of lymphomatoid granulomatosis, grades 1 through 3. In all 10 cases, immunohistochemistry showed that most of the cells-small to medium-sized lymphocytes-were T cells (CD45RO+); however, a much smaller population of medium-sized to large atypical cells were B cells (CD20+). In each case, combined immunohistochemistry and in situ hybridization confirmed the presence of Epstein-Barr virus sequences within B (CD20+) cells and the absence of Epstein-Parr within T-cells (CD45RO+). Polymerase chain reaction analysis for immunoglobulin heavy-chain gene rearrangement identified a monoclonal pattern in six of nine cases tested, whereas analysis for T-cell receptor gamma-chain gene rearrangements was negative in three cases tested. On the basis of these findings, we hypothesize that most cases of lymphomatoid granulomatosis involving the lung represent a proliferation of Epstein-Barr virus infected B-cells with a prominent T-cell reaction and vasculitis, distinguishing these cases from angiocentric ''T-cell lymphomas'' in other sites, such as the head and neck. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT HEMATOPATHOL,WASHINGTON,DC 20306. RP GUINEE, D (reprint author), ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306, USA. NR 65 TC 172 Z9 174 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1994 VL 18 IS 8 BP 753 EP 764 DI 10.1097/00000478-199408000-00001 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA NZ050 UT WOS:A1994NZ05000001 PM 8037289 ER PT J AU WESTERGAARD, GC HOPKINS, WD AF WESTERGAARD, GC HOPKINS, WD TI THEORIES OF MIND AND SELF-RECOGNITION SO AMERICAN PSYCHOLOGIST LA English DT Letter ID CHIMPANZEES PAN-TROGLODYTES C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD, USA. NR 9 TC 0 Z9 0 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD AUG PY 1994 VL 49 IS 8 BP 761 EP 761 PG 1 WC Psychology, Multidisciplinary SC Psychology GA PA480 UT WOS:A1994PA48000012 ER PT J AU DEUTSCH, J GRANGE, E RAPOPORT, SI PURDON, AD AF DEUTSCH, J GRANGE, E RAPOPORT, SI PURDON, AD TI ISOLATION AND QUANTITATION OF LONG-CHAIN ACYL-COENZYME-A ESTERS IN BRAIN-TISSUE BY SOLID-PHASE EXTRACTION SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID COA ESTERS; A ESTERS; RAT; LIVER AB Long-chain acyl-CoA's are important intermediates in fatty acid oxidation and phospholipid metabolism. For quantitative analysis of brain acyl-CoA's, and to avoid decomposition due to high brain acyl-CoA hydrolase activity, a fast and efficient analytical method was developed for isolation and determination of acyl-CoA's. The analysis includes solid-phase extraction by an oligonucleotide purification cartridge and HPLC measurements using a synthetic internal standard. Estimates of concentration in rat brain are oleoyl-CoA (11.0 nmol/g), palmitoyl-CoA (6.0 nmol/g), stearoyl-CoA (4.0 nmol/g), and linoleoyl and arachidonoyl-CoA (2.0 nmol/g) for a total concentration of 23 nmol/g brain. (C) 1994 Academic Press, Inc. C1 HEBREW UNIV JERUSALEM,SCH PHARM,IL-91120 JERUSALEM,ISRAEL. RP DEUTSCH, J (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 18 TC 99 Z9 99 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 AUG 1 PY 1994 VL 220 IS 2 BP 321 EP 323 DI 10.1006/abio.1994.1344 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NY758 UT WOS:A1994NY75800013 PM 7978274 ER PT J AU LEE, SP PORTER, D CHIRIKJIAN, JG KNUTSON, JR HAN, MK AF LEE, SP PORTER, D CHIRIKJIAN, JG KNUTSON, JR HAN, MK TI FLUOROMETRIC ASSAY FOR DNA CLEAVAGE REACTIONS CHARACTERIZED WITH BAMHI RESTRICTION-ENDONUCLEASE SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID FLUORESCENCE ENERGY-TRANSFER; HYBRIDIZATION PROBES; BIOTIN; OLIGONUCLEOTIDES; MOLECULES; JUNCTION AB Fluorescently labeled oligonucleotides and DNA fragments have promise in nucleic acid research with applications that include DNA hybridization, automated DNA sequencing, fluorescence anisotropy, and resonance energy transfer studies. Past concerns with fluorescent-labeled DNA arose from interactions between fluorophores and DNA that result in quenched fluorescence. This quenching phenomenon is most problematic in fluorescence resonance energy transfer studies because quenching of the donor fluorescence could result from either resonance energy transfer or nontransfer effects. In the present study, relief of nontransfer quenching of a 14-mer fluorescein 5-isothiocyanate (FITC)-labeled oligonucleotide containing the BamHI restriction site was characterized with both steady-state and time-resolved fluorescence techniques. The FITC-labeled single strand was best fit by a triexponential decay with lifetimes of 0.5, 2.7, and 4.2 ns. The 4.2-ns component was found to contribute more than 80% of the total steady-state intensity. Upon annealing with an unmodified complementary strand, the contribution from the 4.2-ns component was significantly decreased, resulting in twofold quenching of total fluorescence. We reasoned that this quenching phenomenon should be a reversible process and could be employed to study strand separation processes in molecular biology. Hence, cleavage of the fluorescently labeled substrate was examined using DNase I and BamHI restriction endonuclease. Our results show that the quenched fluorescence is totally recovered upon cleavage (compared to that of the single strand). The extent of cleavage measured by fluorescence was confirmed by nondenaturing polyacrylamide gel electrophoresis analysis. We believe this fluorescence ''dequenching'' technique may be used to quantify the kinetics of other DNA strand separation and cleavage processes in molecular biology. (C) 1994 Academic Press, Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM,WASHINGTON,DC 20007. NHLBI,BETHESDA,MD 20892. NR 25 TC 41 Z9 41 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 1994 VL 220 IS 2 BP 377 EP 383 DI 10.1006/abio.1994.1353 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NY758 UT WOS:A1994NY75800022 PM 7978282 ER PT J AU KATO, K MORIKAWA, H KIMOTO, H KIRK, KL AF KATO, K MORIKAWA, H KIMOTO, H KIRK, KL TI CRYSTAL-STRUCTURE OF O,O'-DIMETHYL-N-TRIFLUOROACETYL-6-TRIFLUOROMETHYLDOPAMINE SO ANALYTICAL SCIENCES LA English DT Article ID PHOTOCHEMICAL TRIFLUOROMETHYLATION; IMIDAZOLES C1 NIDDKD,BETHESDA,MD 20892. RP KATO, K (reprint author), NATL IND RES INST NAGOYA,HIRATE CHO,KITA KU,NAGOYA 462,JAPAN. NR 5 TC 2 Z9 2 U1 1 U2 2 PU JAPAN SOC ANALYTICAL CHEM PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO 141, JAPAN SN 0910-6340 J9 ANAL SCI JI Anal. Sci. PD AUG PY 1994 VL 10 IS 4 BP 693 EP 694 DI 10.2116/analsci.10.693 PG 2 WC Chemistry, Analytical SC Chemistry GA PB414 UT WOS:A1994PB41400033 ER PT J AU LIM, DJ BLUESTONE, CD AF LIM, DJ BLUESTONE, CD TI RECENT ADVANCES IN OTITIS-MEDIA - REPORT OF THE 5TH RESEARCH CONFERENCE - INTRODUCTION SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Editorial Material C1 CHILDRENS HOSP PITTSBURGH,DEPT PEDIAT OTOLARYNGOL,PITTSBURGH,PA 15213. RP LIM, DJ (reprint author), NIDOCD,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1994 VL 103 IS 8 SU 164 BP 6 EP 7 PN 2 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA PC386 UT WOS:A1994PC38600001 ER PT J AU NAUNTON, RF AF NAUNTON, RF TI RECENT ADVANCES IN OTITIS-MEDIA - REPORT OF THE 5TH RESEARCH CONFERENCE - SPECIAL REMARKS SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Editorial Material RP NAUNTON, RF (reprint author), NIDCD,DIV COMMUN SCI & DISORDERS,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1994 VL 103 IS 8 SU 164 BP 8 EP 8 PN 2 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA PC386 UT WOS:A1994PC38600002 ER PT J AU PAPARELLA, MM LIM, DJ ARNOLD, WJ DOYLE, WJ GOYCOOLEA, MV HELLSTROM, SOM HUSSL, B ISHII, T JUNG, TTK KUIJPERS, W SANDO, I TAKASAKA, T AF PAPARELLA, MM LIM, DJ ARNOLD, WJ DOYLE, WJ GOYCOOLEA, MV HELLSTROM, SOM HUSSL, B ISHII, T JUNG, TTK KUIJPERS, W SANDO, I TAKASAKA, T TI ANATOMY, CELL BIOLOGY, AND PATHOLOGY SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID ROUND WINDOW MEMBRANE; EXPERIMENTAL OTITIS-MEDIA; MIDDLE-EAR MUCOSA; EUSTACHIAN-TUBE CARTILAGE; CLEFT-PALATE; HORSERADISH-PEROXIDASE; TYMPANIC MEMBRANES; TEMPORAL BONE; HISTOPATHOLOGY; CHOLESTEATOMA C1 UNIV MINNESOTA, DEPT OTOLARYNGOL, MINNEAPOLIS, MN 55455 USA. NIH, NATL INST DEAFNESS & OTHER COMMUNICAT DISORDERS, BETHESDA, MD 20892 USA. CHILDRENS HOSP PITTSBURGH, DEPT PEDIAT OTOLARYNGOL, PITTSBURGH, PA 15213 USA. UNIV MINNESOTA, SCH MED, DEPT OTOLARYNGOL, MINNEAPOLIS, MN 55455 USA. UNIV INNSBRUCK, DEPT OTOLARYNGOL, A-6020 INNSBRUCK, AUSTRIA. TOKYO WOMENS MED COLL, DEPT OTOLARYNGOL, TOKYO, JAPAN. LOMA LINDA UNIV, DEPT OTOLARYNGOL, LOMA LINDA, CA 92350 USA. UNIV NIJMEGEN, DEPT OTOLARYNGOL, NIJMEGEN, NETHERLANDS. EYE & EAR INST PITTSBURGH, ELIZABETH MCCULLOUGH KNOWLES OPOPATHOL LAB, PITTSBURGH, PA 15213 USA. TOHOKU UNIV, SCH MED, DEPT OTOLARYNGOL, SENDAI 982, JAPAN. RP PAPARELLA, MM (reprint author), TECH UNIV MUNICH, DEPT OTORHINOLARYNGOL, W-8000 MUNICH, GERMANY. NR 77 TC 0 Z9 0 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1994 VL 103 IS 8 SU 164 BP 20 EP 26 PN 2 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA PC386 UT WOS:A1994PC38600005 ER PT J AU OGRA, PL BARENKAMP, SJ MOGI, G PELTON, SI JUHN, SK KARMA, P BAKALETZ, LO BERNSTEIN, JM DEMARIA, TF DIVEN, WF FADEN, H GIEBINK, GS HELLSTROM, SOM HOWIE, VM KLEIN, DL KUIJPERS, W MCINNES, PM PRELLNER, K RYAN, AF RYNNELDAGOO, B AF OGRA, PL BARENKAMP, SJ MOGI, G PELTON, SI JUHN, SK KARMA, P BAKALETZ, LO BERNSTEIN, JM DEMARIA, TF DIVEN, WF FADEN, H GIEBINK, GS HELLSTROM, SOM HOWIE, VM KLEIN, DL KUIJPERS, W MCINNES, PM PRELLNER, K RYAN, AF RYNNELDAGOO, B TI MICROBIOLOGY, IMMUNOLOGY, BIOCHEMISTRY, AND VACCINATION SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 5th Research Conference on Recent Advances in Otitis Media CY MAY 20-24, 1991 CL FT LAUDERDALE, FL SP Ohio State Univ, Coll Med, Dept Otolaryngol, Ohio State Univ, Coll Med, Ctr Continuing Med Educ ID ACUTE OTITIS-MEDIA; NONTYPABLE HEMOPHILUS-INFLUENZAE; MIDDLE-EAR EFFUSIONS; RESPIRATORY VIRUS-INFECTION; PROTEIN CONJUGATE VACCINE; OUTER-MEMBRANE PROTEIN; STREPTOCOCCUS-PNEUMONIAE; HAEMOPHILUS-INFLUENZAE; IMMUNE-RESPONSE; BRANHAMELLA-CATARRHALIS C1 UNIV TEXAS,MED BRANCH,DEPT PEDIAT,GALVESTON,TX 77550. CARDINAL GLENNON MEM HOSP CHILDREN,DIV INFECT DIS,ST LOUIS,MO 63104. OITA MED UNIV,DEPT OTOLARYNGOL,OITA,JAPAN. BOSTON UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02118. UNIV MINNESOTA,SCH MED,DEPT OTOLARYNGOL,MINNEAPOLIS,MN 55455. UNIV HELSINKI,CENT HOSP,DEPT OTORHINOLARYNGOL,HELSINKI,FINLAND. OHIO STATE UNIV,COLL MED,OTOL RES LAB,COLUMBUS,OH 43210. SUNY COLL BUFFALO,DEPT COMMUN DISORDERS & SCI,BUFFALO,NY 14222. UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA. CHILDRENS HOSP,DIV INFECT DIS,BUFFALO,NY 14222. UNIV MINNESOTA,DEPT PEDIAT & OTOLARYNGOL,MINNEAPOLIS,MN 55455. CHILDRENS HOSP,DEPT PEDIAT,GALVESTON,TX. UNIV NIJMEGEN,DEPT OTOLARYNGOL,NIJMEGEN,NETHERLANDS. UNIV LUND HOSP,DEPT OTORHINOLARYNGOL,S-22185 LUND,SWEDEN. UNIV CALIF SAN DIEGO,DEPT SURG OTOLARYNGOL & NEUROSCI,LA JOLLA,CA 92093. HUDDINGE HOSP,DEPT OTOLARYNGOL,S-14186 HUDDINGE,SWEDEN. RP OGRA, PL (reprint author), NIAID,ROCKVILLE,MD, USA. OI Barenkamp, Stephen/0000-0002-3054-8910 NR 115 TC 2 Z9 2 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1994 VL 103 IS 8 SU 164 BP 27 EP 43 PN 2 PG 17 WC Otorhinolaryngology SC Otorhinolaryngology GA PC386 UT WOS:A1994PC38600006 ER PT J AU GIEBINK, GS MEYERHOFF, WL CANAFAX, DM HOWIE, VM LUNDGREN, K MAW, AR NAUNTON, RF NELSON, JD PARADISE, JL SHURIN, PA THOMSEN, J TOS, M AF GIEBINK, GS MEYERHOFF, WL CANAFAX, DM HOWIE, VM LUNDGREN, K MAW, AR NAUNTON, RF NELSON, JD PARADISE, JL SHURIN, PA THOMSEN, J TOS, M TI TREATMENT SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 5th Research Conference on Recent Advances in Otitis Media CY MAY 20-24, 1991 CL FT LAUDERDALE, FL SP Ohio State Univ, Coll Med, Dept Otolaryngol, Ohio State Univ, Coll Med, Ctr Continuing Med Educ ID ACUTE OTITIS-MEDIA; MIDDLE-EAR EFFUSION; RANDOMIZED CLINICAL-TRIAL; TYMPANOSTOMY-TUBE PLACEMENT; TRIMETHOPRIM-SULFAMETHOXAZOLE; DOUBLE-BLIND; GLUE EAR; CHILDREN; ADENOIDECTOMY; AMOXICILLIN C1 UNIV TEXAS,SOUTHWESTERN MED CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,DALLAS,TX 75235. UNIV MINNESOTA,COLL PHARM,DEPT PHARM PRACTICE,MINNEAPOLIS,MN 55455. CHILDRENS HOSP,DEPT PEDIAT,GALVESTON,TX. CENT HOSP KRISTIANSTAD,DEPT OTOLARYNGOL,KRISTIANSTAD,SWEDEN. BRISTOL ROYAL INFIRM & GEN HOSP,DEPT OTOLARYNGOL,BRISTOL,AVON,ENGLAND. NIH,CTR CLIN,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,DEPT PEDIAT,PITTSBURGH,PA. COLUMBIA UNIV,COLL PHYS & SURG,DEPT CLIN PEDIAT,NEW YORK,NY. GENTOFTE UNIV HOSP,DEPT OTOLARYNGOL HEAD & NECK SURG,HELLERUP,DENMARK. GENTOFTE UNIV HOSP,DEPT OTOLARYNGOL,HELLERUP,DENMARK. RP GIEBINK, GS (reprint author), UNIV MINNESOTA,DEPT PEDIAT & OTOLARYNGOL,MINNEAPOLIS,MN 55455, USA. NR 90 TC 2 Z9 2 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1994 VL 103 IS 8 SU 164 BP 58 EP 66 PN 2 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA PC386 UT WOS:A1994PC38600010 ER PT J AU TEMECK, BK VENZON, DJ MOSKALUK, CA PASS, HI AF TEMECK, BK VENZON, DJ MOSKALUK, CA PASS, HI TI THORACOTOMY FOR PULMONARY MYCOSES IN NON-HIV-IMMUNOSUPPRESSED PATIENTS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 1994 CL NEW ORLEANS, LA SP SOC THORAC SURGEONS ID IMMUNOCOMPROMISED PATIENTS; FUNGAL-INFECTIONS; ASPERGILLOSIS; SPECTRUM; DISEASE; HOST AB Pulmonary mycoses can be life threatening in patients who are in an immunocompromised state stemming from defective host defenses or the use of certain treatment regimens. In 36 immunosuppressed patients undergoing thoracotomy for the treatment of pulmonary fungal disease, the underlying cause of immunosuppression was malignancy (n = 9), Wegener's granulomatosis (n = 4), hematologic disorders (aplastic anemia, 5-Q minus syndrome, or myelofibrosis) (n = 6), or chronic granulomatous disease of childhood (n = 17). The mean age of the patients was 25 years, and 89% were symptomatic (fever, n = 27; cough, n = 20; chest pain, n = 14; and other, n = 13%. Chest x-ray studies revealed the presence of cavitary disease (n = 7), a mass (n = 8), infiltrates (n = 20), or cavity and infiltrate (n = 1). A preoperative diagnosis was lacking in 23 of the 36 patients. Procedures included wedge biopsy (n = 13), segmentectomy with or without wedge or chest wall resection (n = 5), lobectomy with or without chest wall resection (n = 16), wedge resection plus completion pneumonectomy (n = 1), and segmentectomy plus completion pneumonectomy (n = 1). Fungi identified included Aspergillus (n = 23), Zygomycetes (n = 4), Cryptococcus (n = 3), and other (n = 6; 1 each), and specific antifungal treatment was instituted in 34 of the patients (94%). The 31% operative tie, <30-day or inhospital) mortality was chiefly due to multiorgan system failure (9/11). Univariate analysis identified the following as prognostic of death during hospitalization: underlying hematologic disease (p(2) = 0.012), angioinvasive disease (p(2) = 0.0064), treatment with chemotherapy and steroids (p(2) = 0.052), and a granulocyte percentage of 30% or less or a granulocyte count of 100 or less (p(2) = 0.048). Moreover, multivariate analysis revealed that angioinvasion correlated with all risk factors and operative mortality. Nineteen patients are still alive at a mean follow-up period of 2.8 years. These data reinforce the risk of operation for the treatment or diagnosis of angioinvasive fungal disease in selected groups of immunosuppressed patients, and the need for improved pharmacologic agents in these high-risk populations. C1 NCI,DEPT SURG PATHOL,BIOSTAT & DATA MANAGEMENT SECT,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 19 TC 18 Z9 19 U1 0 U2 0 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 AUG PY 1994 VL 58 IS 2 BP 333 EP 338 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PD589 UT WOS:A1994PD58900011 PM 8067828 ER PT J AU TAGLIAFERRI, P CARAGLIA, M MURARO, R PINTO, A BUDILLON, A ZAGONEL, V BIANCO, AR AF TAGLIAFERRI, P CARAGLIA, M MURARO, R PINTO, A BUDILLON, A ZAGONEL, V BIANCO, AR TI PHARMACOLOGICAL MODULATION OF PEPTIDE GROWTH-FACTOR RECEPTOR EXPRESSION ON TUMOR-CELLS AS A BASIS FOR CANCER-THERAPY SO ANTI-CANCER DRUGS LA English DT Review DE CYTOKINES; DRUGS; EGF-R; IL-2-R; PEPTIDE GROWTH FACTOR RECEPTORS; TARGETING MODULATION ID MULTICHAIN INTERLEUKIN-2 RECEPTOR; REED-STERNBERG CELLS; MONOCLONAL-ANTIBODY; HODGKINS-DISEASE; TRANSFERRIN RECEPTOR; PSEUDOMONAS EXOTOXIN; ALPHA-INTERFERON; HUMAN-BREAST; SIGNAL TRANSDUCTION; ENHANCED EXPRESSION AB Membrane receptors for peptide growth factor receptors (PGF-R) play a crucial role in the regulation of cancer cell proliferation and may behave as tumor associated antigens (TAA), which are currently regarded as specific targets for immunodetection and immunotherapy of human cancer. PGF-R are often more expressed by tumor cells than by normal counterparts and, by analogy to TAA, their surface expression may be regulated by cytokines. Moreover, the biological functions and specific ligands of most PGF-R are presently well elucidated as opposed to the great majority of TAA. PGF-R may, therefore, represent ideal cellular targets for at least two different therapeutic approaches: (i) naked or conjugated monoclonal antibodies and (ii) genetically engineered fusion proteins composed of PGF-R physiological ligands linked to genetically modified bacterial toxins. To date, clinical studies based on targeting of receptors for epidermal growth factor and interleukin-2 on tumor cells have been performed. Information from such studies suggests that PGF-R as well as TAA targeting strategies are clinically feasible, but that they still have to be optimized. A variety of host and tumor factors which affect targeting of neoplastic cells have been recently identified. For instance, it has been demonstrated that the antigenic density of the targeted molecule at the tumor cell surface is an important factor. In this view upregulation of PGF-R on cancer cells could be of major clinical advantage in immunotargeting. It has been reported that several cytokines and chemical compounds can induce PGF-R modulation on tumor cells. This paper reviews therapeutic opportunities related to the pharmacologic modulation of PGF-R expression. In addition a mechanistic hypothesis regarding PGF-R upregulation induced by cytostatic drugs and cytokines is proposed. C1 UNIV G DANNUNZIO,FAC MED,IST PATOL UMANA & MED SOCIALE,CHIETI,ITALY. IST NAZL RICOVERO & CURA CARATTERE SCI,CTR RIFERIMENTO ONCOL,DIV ONCOL MED,I-33081 AVIANO,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. IST NAZL RICOVERO & CURA CARATTERE SCI,CTR RIFERIMENTO ONCOL,UNITA OPERAT LEUCEMIE,I-33081 AVIANO,ITALY. RP TAGLIAFERRI, P (reprint author), UNIV FEDERICO II NAPOLI,FAC MED,CATTEDRA ONCOL MED,VIA S PANSINI 5,I-80131 NAPLES,ITALY. RI zagonel, vittorina/F-4226-2014; Caraglia, Michele/N-5670-2015; OI zagonel, vittorina/0000-0002-0829-2525; Caraglia, Michele/0000-0003-2408-6091; Budillon, Alfredo/0000-0002-6330-6053 NR 164 TC 21 Z9 21 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD AUG PY 1994 VL 5 IS 4 BP 379 EP 393 DI 10.1097/00001813-199408000-00001 PG 15 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NZ584 UT WOS:A1994NZ58400001 PM 7949241 ER PT J AU BLAGOSKLONNY, MV NECKERS, LM AF BLAGOSKLONNY, MV NECKERS, LM TI OLIGONUCLEOTIDES PROTECT CELLS FROM THE CYTOTOXICITY OF SEVERAL ANTICANCER CHEMOTHERAPEUTIC DRUGS SO ANTI-CANCER DRUGS LA English DT Article DE ANTINEOPLASTIC DRUGS; ANTISENSE; CYTOPROTECTION; DRUG INTERACTION; OLIGONUCLEOTIDES ID ACTINOMYCIN-D; BINDING; DNA AB The possibility of inhibiting gene expression with antisense oligonucleotides (AS ODNs) in combination with more conventional chemotherapy is a very attractive modality in oncology. However, possible interaction between the ODN and drug must be considered. Here we show that ODNs protect cells from the cytostatic/cytotoxic action of actinomycin D (AMD), adriamycin, daunomycin or quinacrine, but not mitomycin, camptothecin, vincristine, cisplatin, etoposide (VP-16) or cycloheximide. The cytoprotective effect depends on ODN length as well as ability to interact directly with the cytotoxic drug and is only slightly sequence selective. RP BLAGOSKLONNY, MV (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 9 TC 14 Z9 14 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD AUG PY 1994 VL 5 IS 4 BP 437 EP 442 DI 10.1097/00001813-199408000-00008 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NZ584 UT WOS:A1994NZ58400008 PM 7949248 ER PT J AU DRUSANO, GL BALIS, FM GITTERMAN, SR PIZZO, PA AF DRUSANO, GL BALIS, FM GITTERMAN, SR PIZZO, PA TI QUANTITATIVE RELATIONSHIPS BETWEEN ZIDOVUDINE EXPOSURE AND EFFICACY AND TOXICITY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; AZIDOTHYMIDINE AZT; HIV-INFECTION; DOUBLE-BLIND; INFUSION; CHILDREN; PHASE AB We examined the relationship between the concentrations of zidovudine in plasma given by continuous intravenous infusion to human immunodeficiency virus-positive pediatric patients and a surrogate marker of outcome (measured by the increase in the number of CD4-positive T cells) as well as drug-mediated toxicity (change in granulocyte count). The return of CD4-positive T cells was most strongly related to the number of these cells present at the start of therapy. Drug concentration data added little explanatory power to this relationship, indicating that the effect of zidovudine was near maximal throughout the range of concentrations examined. The change in granulocyte count was significantly correlated with zidovudine concentration both from weeks 1 through 8 and from weeks 8 through 12. These findings imply that it may be wise to stratify phase I antiretrovirus drug trials for the entry level of CD4-positive T cells if pharmacodynamic relationships with this marker as the dependent variable are to be sought. Continued efforts need to be made to derive quantitative relationships between drug exposure and measures of both efficacy and toxicity so that the maximal amount of information is derived from small phase I studies. C1 UNIV MARYLAND,DIV INFECT DIS,PROGRAM CLIN PHARMACOL,BALTIMORE,MD. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP DRUSANO, GL (reprint author), ALBANY MED COLL,DIV CLIN PHARMACOL,ALBANY,NY 12208, USA. NR 17 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1994 VL 38 IS 8 BP 1726 EP 1731 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NZ449 UT WOS:A1994NZ44900006 PM 7986002 ER PT J AU ROSNER, JL STORZ, G AF ROSNER, JL STORZ, G TI EFFECTS OF PEROXIDES ON SUSCEPTIBILITIES OF ESCHERICHIA-COLI AND MYCOBACTERIUM-SMEGMATIS TO ISONIAZID SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SALMONELLA-TYPHIMURIUM; OXIDATIVE STRESS; TUBERCULOSIS; RESISTANT; MUTANTS; TRANSFORMATION; EXTRACTS; REGULON; AURUM AB Escherichia coli strains were previously found to be susceptible to the antituberculosis drug isonicotinic acid hydrazide (isoniazid [INH]) when they carried certain mutations that also sensitize them to peroxides: a deletion in oxyR, a redox-sensitive regulator of hydrogen peroxide-inducible genes, or mutations in both katG and ahpCF, OxyR-regulated genes encoding hydroperoxidase I, and an alkyl hydroperoxide reductase. To test whether INH, like peroxides, activates OxyR, the effect of INH on OxyR regulation was examined. Primer extension assays showed that transcription of the OxyR-regulated oxyS gene was not significantly induced by INH in wild-type cells, indicating that INH does not activate OxyR. However, the INH-susceptibie katG ahpCF mutant strain was found to have constitutively high levels of oxyS transcription. This suggested that the lack of peroxidase expression in these strains allows endogenous oxidants to accumulate, and this leads not only to constitutive OxyR activation but also to INH susceptibility. Consistent with this concept, hydrogen peroxide or cumene hydroperoxide potentiated the INH susceptibilities of wild-type cells, while the antioxidant ascorbic acid protected the susceptible katG ahpCF mutant strain from INH. Superoxide radicals, generated by paraquat, did not enhance the INH susceptibilities of wild-type cells. Hydrogen peroxide also potentiated the INH susceptibilities of susceptible and resistant (katG mutant) Mycobacterium smegmatis strains. Our results suggest that INH is converted to a more active drug by reaction with peroxides and that the INH susceptibilities of enterobacteria and mycobacteria are mechanistically related. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP ROSNER, JL (reprint author), NIDDKD,MOLEC BIOL LAB,RM 333,BLDG 5,BETHESDA,MD 20892, USA. OI Storz, Gisela/0000-0001-6698-1241 NR 19 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1994 VL 38 IS 8 BP 1829 EP 1833 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NZ449 UT WOS:A1994NZ44900021 PM 7986015 ER PT J AU ASAWAMAHASAKDA, W ITTARAT, I PU, YM ZIFFER, H MESHNICK, SR AF ASAWAMAHASAKDA, W ITTARAT, I PU, YM ZIFFER, H MESHNICK, SR TI REACTION OF ANTIMALARIAL ENDOPEROXIDES WITH SPECIFIC PARASITE PROTEINS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; ARTEMISININ QINGHAOSU; SUPEROXIDE-DISMUTASE; SURFACE; DRUG; ERYTHROCYTES; ARTEETHER; ANTIGEN; CULTURE AB The endoperoxides are a new class of antimalarial agents, of which artemisinin (qinghaosu) is the prototype. We have previously shown that artemisinin is capable of alkylating proteins in model reactions. In the present study, we showed that when Plasmodium falciparum-infected erythrocytes are treated with a radiolabeled antimalarial endoperoxide, either arteether, dihydroartemisinin, or Ro 42-1611 (arteflene), the radioactivity is largely coverted into a form which can be extracted with sodium dodecyl sulfate (SDS). Autoradiograms of SDS-polyacrylamide gels showed that six malarial proteins are radioactively labeled by the three endoperoxides. This labeling occurs at physiological concentrations of drug and is not stage nor strain specific. The labeled proteins were not the most abundant proteins seen on Coomassie-stained gels. No proteins were labeled when uninfected erythrocytes were treated with these drugs, nor when infected erythrocytes were treated with the inactive analog deoxyarteether. Thus, the antimalarial endoperoxides appear to react with specific malarial proteins. C1 UNIV MICHIGAN,SCH PUBL HLTH,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI26848] NR 31 TC 166 Z9 168 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1994 VL 38 IS 8 BP 1854 EP 1858 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NZ449 UT WOS:A1994NZ44900026 PM 7986020 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI DEGRADATION AND DISPOSAL OF SOME ENZYME-INHIBITORS SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Note DE SAFETY; DEGRADATION; STABILITY; ENZYME INHIBITORS; PMSF; APMSF; AEBSF; TLCK; TPCK; HPLC ID FLUORIDE AB Five enzyme inhibitors (phenylmethylsulfonyl fluoride, 4-amidinophenylmethanesulfonyl fluoride, 4-(2-aminoethyl)benzenesulfonyl fluoride, Nor-p-tosyl-L-lysine chloromethyl ketone, and N-tosyl-L-phenylalanine chloromethyl ketone) in buffer, DMSO, or stock solutions were completely degraded by adding 1M NaOH and the final reaction mixtures were not mutagenic. The stability of these compounds decreased as the pH increased. RP LUNN, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ENVIRONM CONTROL & RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [NCI NO1-CO-74102] NR 7 TC 2 Z9 2 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0273-2289 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD AUG PY 1994 VL 48 IS 2 BP 57 EP 59 DI 10.1007/BF02796162 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PE226 UT WOS:A1994PE22600001 PM 7944352 ER PT J AU IMAI, Y YANAGISHITA, M HASCALL, VC AF IMAI, Y YANAGISHITA, M HASCALL, VC TI MEASUREMENT OF CONTRIBUTION FROM INTRACELLULAR CYSTEINE TO SULFATE IN PHOSPHOADENOSINE PHOSPHOSULFATE IN RAT OVARIAN GRANULOSA-CELLS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID DERMATAN SULFATE; CHONDROITIN SULFATES; SKIN FIBROBLASTS; HYALURONIC-ACID; PROTEOGLYCANS; SULFUR; CHROMATOGRAPHY; CULTURE; SO42 AB Synthesis of the large dermatan sulfate (DS) proteoglycan by rat ovarian granulosa cells was studied using metabolic radiolabel precursors in culture media with varying concentrations of environmental sulfate (20-800 mu M) and cysteine (130 and 650 mu M). Experiments using [H-3]glucosamine and [S-35]sulfate showed that the average size of the DS chains and the rate of DS proteoglycan synthesis were independent of the sulfate and cysteine concentrations in the medium. Experiments with [S-35]cysteine were then used to determine the contribution that metabolic conversion of cysteine sulfur to sulfate makes to the 3'-phosphoadenosine 5'-phosphosulfate (PAPS) pool which provides the substrate for sulfoester formation in DS synthesis. When S-35 in cysteine is metabolized into [S-35]PAPS, the specific activity is reduced from that of the [S-35]cysteine pool, by dilution with other sulfur sources such as extracellular sulfate, and this dilution factor directly reflects the contribution of cysteine to the PAPS pool. The decreases of S-35 specific activity were measured under various sulfate-depleted and cysteine-supplemented conditions by comparing the specific activity of [S-35]sulfate ester in the DS chains with that of [S-35]cysteine residues in the core protein of the DS proteoglycan. The contribution of sulfur in cysteine to the intracellular PAPS pool was 0.03% in culture medium with normal sulfate (800 mu M). Depleted environmental sulfate (20 mu M) and increased cysteine supply (650 mu M) only increased the sulfur contribution from cysteine to PAPS up to 0.74 and 1.5%, respectively, even though the DS chains were greatly undersulfated (55 and 82% of the control value). Thus, the source of sulfur in the intracellular pool of PAPS was mainly derived from environmental sulfate, and the contribution from cysteine was minimal in these cells. (C) 1994 Academic Press, Inc. C1 NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 1994 VL 312 IS 2 BP 392 EP 400 DI 10.1006/abbi.1994.1324 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX805 UT WOS:A1994NX80500010 PM 8037451 ER PT J AU YANCEY, KB AF YANCEY, KB TI FROM BEDSIDE TO BENCH AND BACK - THE DIAGNOSIS AND BIOLOGY OF BULLOUS DISEASES SO ARCHIVES OF DERMATOLOGY LA English DT Article ID DYSTROPHIC EPIDERMOLYSIS-BULLOSA; PEMPHIGUS-VULGARIS; BASEMENT-MEMBRANES; PASSIVE TRANSFER; GENETIC-LINKAGE; CELL-ADHESION; VII COLLAGEN; ANTIGEN; AUTOANTIBODIES; ACQUISITA AB The history of dermatology is replete with examples where astute physicians have made key observations that have led to the recognition of distinct diseases and syndromes. While clinicians may be either lumpers or splitters, their unifying theme has been that of identifying common elements among patients to assist in their diagnosis, classification, and treatment. Light microscopy, electron microscopy, immunopathologic techniques, and molecular biology have provided dermatologists additional data to assist in their analysis of incompletely understood and poorly classified skin diseases. Application of these techniques over the past 40 years to patients with bullous diseases has led to the development of many new concepts including the following: (1) patients with bullous diseases have autoantibodies that target disease-specific antigens that represent important structural components of normal human skin; (2) autoantibodies from patients with certain-bullous diseases are pathogenic in experimental animal models; and (3) some of the same structural proteins targeted by autoantibodies in patients with acquired autoimmune bullous diseases are mutated in patients with inherited bullous diseases. An overview of these concepts is the subject of this brief review. RP YANCEY, KB (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 40 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 1994 VL 130 IS 8 BP 983 EP 987 DI 10.1001/archderm.130.8.983 PG 5 WC Dermatology SC Dermatology GA PC020 UT WOS:A1994PC02000003 PM 8053715 ER PT J AU KRAEMER, KH LEE, MM ANDREWS, AD LAMBERT, WC AF KRAEMER, KH LEE, MM ANDREWS, AD LAMBERT, WC TI THE ROLE OF SUNLIGHT AND DNA-REPAIR IN MELANOMA AND NONMELANOMA SKIN-CANCER - THE XERODERMA-PIGMENTOSUM PARADIGM SO ARCHIVES OF DERMATOLOGY LA English DT Article ID COCKAYNE-SYNDROME CELLS; PHOTOPRODUCTS; MUTATIONS AB Background and Design: The frequency of melanoma and nonmelanoma skin cancer is increasing rapidly in the United States. However, the linkage of these cancers to sun exposure has been questioned because of differences in anatomic site distribution. To obtain insights into the development of these skin cancers, we examined reports of 132 patients with xeroderma pigmentosum (XP), an inherited cancer-prone, DNA repair-deficient disorder with marked clinical and laboratory UV hypersensitivity. Results: Malignant skin neoplasms were present in 70% of the patients with XP at a median age of 8 years, which is 50 years earlier than in the US white population. Fifty-seven percent of the patients had basal cell or squamous cell carcinoma, and 22% had melanoma. The frequency of melanomas, like the frequency of nonmelanoma skin cancers (basal cell and squamous cell carcinomas), anterior eye cancers, and tongue cancers, but unlike that of internal neoplasms, was increased 1000-fold or more in patients with XP who were younger than 20 years. As in the general population, the anatomic distribution of melanomas was different from that of nonmelanoma in the patients with XP. Conclusions: These data suggest that (1) DNA repair plays a major role in the prevention of cutaneous cancers in the general population and (2) sunlight exposure is responsible for the induction of melanoma as well as nonmelanoma skin cancer in patients with XP, although acting by different mechanisms for the two types of skin cancer. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT DERMATOL,NEW YORK,NY. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT LAB MED & PATHOL,NEWARK,NJ 07103. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT DERMATOL,NEWARK,NJ 07103. RP KRAEMER, KH (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 12 TC 349 Z9 358 U1 2 U2 56 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 1994 VL 130 IS 8 BP 1018 EP 1021 DI 10.1001/archderm.130.8.1018 PG 4 WC Dermatology SC Dermatology GA PC020 UT WOS:A1994PC02000009 PM 8053698 ER PT J AU DIGIOVANNA, JJ BALE, SJ AF DIGIOVANNA, JJ BALE, SJ TI CLINICAL HETEROGENEITY IN EPIDERMOLYTIC HYPERKERATOSIS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID KERATIN GENE-CLUSTER; INVOLVEMENT; MUTATIONS; LINKAGE AB Background and Design: Epidermolytic hyperkeratosis (EHK) is a rare autosomal dominant disorder of cornification. While different clinical presentations of EHK have been described, the distinctions have not been clear. We have examined 52 patients with EHK from 21 families in an effort to define and characterize the specific clinical features of this disorder. Results: We found that several features were useful for separating patients with EHK into clinical groups. The most distinctive characteristic was presence vs absence of severe palmoplantar hyperkeratosis. Twenty-nine patients in six families had this finding and were grouped into ''PS types'' (those with severe palm/sole hyperkeratosis). The remaining 23 patients (from 15 families) were classified as ''NPS types'' (those without severe palm/sole hyperkeratosis). We identified three distinct PS types and three distinct NPS types. The classification was always found to be consistent in all affected family members. In those families in which mutations were defined, keratin 1 mutations were identified in the PS types and keratin 10 mutations in the NPS types. Conclusions: We were able to classify our cohort of 52 patients with EHK from 21 families into distinct types. There was a correlation between presence or absence of severe palm/sole hyperkeratosis and the specific keratin involved. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP DIGIOVANNA, JJ (reprint author), NIAMSD,SKIN BIOL LAB,GENET STUDIES SECT,BLDG 6,ROOM 429,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 85 Z9 88 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 1994 VL 130 IS 8 BP 1026 EP 1035 DI 10.1001/archderm.130.8.1026 PG 10 WC Dermatology SC Dermatology GA PC020 UT WOS:A1994PC02000011 PM 8053700 ER PT J AU SUNDERLAND, T COHEN, RM MOLCHAN, S LAWLOR, BA MELLOW, AM NEWHOUSE, PA TARIOT, PN MUELLER, EA MURPHY, DL AF SUNDERLAND, T COHEN, RM MOLCHAN, S LAWLOR, BA MELLOW, AM NEWHOUSE, PA TARIOT, PN MUELLER, EA MURPHY, DL TI HIGH-DOSE SELEGILINE IN TREATMENT-RESISTANT OLDER DEPRESSIVE PATIENTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MONOAMINE-OXIDASE INHIBITORS; PRETREATMENT ORTHOSTATIC HYPOTENSION; ALZHEIMER-TYPE DEMENTIA; L-DEPRENYL; GERIATRIC DEPRESSION; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; BLOOD-PRESSURE; HUMAN-BRAIN; TREATMENT RESPONSE AB Background: We examined the effect of high-dose selegiline in 16 treatment-resistant older depressive patients. We hypothesized that selegiline, at a dosage of 60 mg/d, would be at least partially effective but that the higher doses would not maintain the monoamine oxidase B selectivity observed with the lower doses of selegiline. Methods: Sixteen treatment-resistant subjects (mean [+/-SD] age, 65.6+/-9.3 years) entered a double-blind, randomized, crossover study of placebo vs 3 weeks of selegiline at a dosage of 60 mg/d. Objective measures of mood and behavior were obtained in all subjects, and 10 of the subjects underwent repeated lumbar punctures for analysis of monoamine metabolites in the cerebrospinal fluid. Results: Objective measures of mood and behavior revealed significant improvement in the Hamilton Depression Rating Scale score (37.4% decrease), the Global Depression score (22.7% decrease), and the Brief Psychiatric Rating Scale score (19.3% decrease); subjective behavioral measures, however, did not show significant improvement during the 3-week medication trial. Cerebrospinal fluid values revealed a statistically significant drop in 3-methoxy-4-hydroxyphenylglycol (51%) and 5-hydroxyindoleacetic acid (17%) levels, and there was a significant lowering of systolic blood pressure on standing (15%), but these changes were not accompanied by clinical side effects. Conclusions: Our results suggest that high-dose selegiline can be an effective antidepressant in treatment-resistant older depressive patients. While the selegiline dose required has nonselective monoamine oxidase effects and thus would not be free of possible tyramine interactions, other advantages suggest that further investigations with selegiline are warranted in this population. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. ST JAMES HOSP,DEPT PSYCHIAT,DUBLIN 8,IRELAND. UNIV MICHIGAN,SCH MED,DEPT PSYCHIAT,ANN ARBOR,MI. UNIV VERMONT,SCH MED,DEPT PSYCHIAT,BURLINGTON,VT 05405. UNIV ROCHESTER,MED CTR,DEPT PSYCHIAT,ROCHESTER,NY 14642. RP SUNDERLAND, T (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,GERIATR PSYCHIAT SECT,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Newhouse, Paul/J-4597-2014 NR 79 TC 86 Z9 88 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1994 VL 51 IS 8 BP 607 EP 615 PG 9 WC Psychiatry SC Psychiatry GA PB415 UT WOS:A1994PB41500002 PM 7519005 ER PT J AU MARANGELL, LB GEORGE, MS BISSETTE, G PAZZAGLIA, P HUGGINS, T POST, RM AF MARANGELL, LB GEORGE, MS BISSETTE, G PAZZAGLIA, P HUGGINS, T POST, RM TI CARBAMAZEPINE INCREASES CEREBROSPINAL-FLUID THYROTROPIN-RELEASING-HORMONE LEVELS IN AFFECTIVELY ILL PATIENTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; AFFECTIVE-ILLNESS; THYROID-FUNCTION; ENDOGENOUS-DEPRESSION; TRH AB Background: Thyrotropin-releasing hormone is an endogenous tripeptide with endocrine-independent neurophysiologic properties that may be relevant to affective or seizure disorders. We studied the effect of carbamazepine, which has both mood-stabilizing and anticonvulsant properties, on cerebrospinal fluid thyrotropin-releasing hormone levels in affectively ill patients. Method: Paired cerebrospinal fluid samples were collected from nine inpatients with mood disorders, both while medication free and while taking carbamazepine for an average of longer than 1 month at 950 mg/d, achieving blood levels of 8.8 mg/L. Results: Carbamazepine treatment was consistently and significantly associated with increased cerebrospinal fluid thyrotropin-releasing hormone levels (P<.0001). Conclusion: As carbamazepine-induced increases in thyrotropin-releasing hormone levels could be relevant to either its psychotropic or anticonvulsant properties, further clinical and preclinical investigation of this finding appears indicated. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. FU NIMH NIH HHS [MH-45975] NR 32 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1994 VL 51 IS 8 BP 625 EP 628 PG 4 WC Psychiatry SC Psychiatry GA PB415 UT WOS:A1994PB41500004 PM 8042911 ER PT J AU FENTON, WS WYATT, RJ MCGLASHAN, TH AF FENTON, WS WYATT, RJ MCGLASHAN, TH TI RISK-FACTORS FOR SPONTANEOUS DYSKINESIA IN SCHIZOPHRENIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TARDIVE-DYSKINESIA; NEGATIVE SYMPTOMS; INVOLUNTARY MOVEMENTS; NATURAL-HISTORY; NEUROLEPTIC DRUGS; NONDEFICIT FORMS; DEFICIT SYNDROME; DISORDERS; ABNORMALITIES; PARADIGMS AB Objective: We describe the prevalence, clinical correlates, and prognostic significance of spontaneous dyskinesias among 100 patients with schizophrenia from the Chestnut Lodge Follow-up Study who had never received treatment with neuroleptic agents up to and including the baseline assessment. Design: Extensive case records were screened and descriptions of abnormal movements were recorded verbatim for blind rating. Neuroleptic-naive patients with and without abnormal oral-facial movements were compared across sign and symptom, schizophrenia subtype, and illness natural history variables. Results: Excluding three patients with motor symptoms who had a history of neurologic illness or injury and three who had received prochlorperazine maleate therapy (Compazine), 23% of patient records documented some form of movement disorder; 15% documented oral-facial dyskinesias with sufficient detail so that their presence was considered nearly certain. Compared with patients with schizophrenia without oral-facial movements, patients with oral-facial dyskinesias were more likely to demonstrate a lower IQ score, had more negative symptoms at index admission, and were more symptomatic at follow-up an average of 23 years later. Both the classic hebephrenic schizophrenia subtype and Carpenter's Criteria for the Deficit Syndrome defined high-risk groups for spontaneous oral-facial dyskinesia. Conclusions: In previous studies, intellectual impairment and negative symptoms have been described as risk factors for neuroleptic-induced tardive dyskinesia. The present data, however, suggest that in many cases oral-facial dyskinesias in patients with intellectual impairment and negative symptoms may actually represent spontaneous movement disorders associated with hebephrenic or deficit forms of schizophrenia. C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,WASHINGTON,DC. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. YALE UNIV,INST PSYCHIAT,NEW HAVEN,CT. RP FENTON, WS (reprint author), CHESTNUT LODGE RES INST,500 W MONTGOMERY AVE,ROCKVILLE,MD 20850, USA. NR 54 TC 100 Z9 100 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1994 VL 51 IS 8 BP 643 EP 650 PG 8 WC Psychiatry SC Psychiatry GA PB415 UT WOS:A1994PB41500006 PM 8042913 ER PT J AU SCHWANKHAUS, JD KATZ, DA ELDRIDGE, R SCHLESINGER, S MCFARLAND, H AF SCHWANKHAUS, JD KATZ, DA ELDRIDGE, R SCHLESINGER, S MCFARLAND, H TI CLINICAL AND PATHOLOGICAL FEATURES OF AN AUTOSOMAL-DOMINANT, ADULT-ONSET LEUKODYSTROPHY SIMULATING CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS SO ARCHIVES OF NEUROLOGY LA English DT Article ID TOMOGRAPHY; DISEASE AB Objective: To study the clinical and pathological features of a kindred with an adult-onset autosomal dominant leukodystrophy. Patients: Five symptomatic and nine asymptomatic at-risk members of the kindred. Interventions: Subjects underwent detailed histories and general and neurologic examinations. Further evaluation included electroencephalography, evoked potentials, electromyography, autonomic testing, and analysis of serum, urine, and cerebrospinal fluid. One patient underwent sural nerve biopsy and analysis. Another, previously studied patient, underwent a limited autopsy. Results: Cerebellar and pyramidal dysfunction began in the fourth and fifth decades of life; subtle autonomic symp-toms were often present years earlier. Frontal lobe dysfunction and abnormalities of the central visual pathways were mild and of late onset. Sensorineural hearing loss was common. The peripheral nervous system was spared. Autopsy results of one patient revealed severe degeneration of the white matter at all levels of the neuraxis, but most prominent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations failed to show evidence of a specific pathogenetic mechanism or etiology. Conclusion: This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,INTERINST MED GENET PROGRAM,BETHESDA,MD 20892. RP SCHWANKHAUS, JD (reprint author), TEXAS TECH UNIV,HLTH SCI CTR,DEPT MED & SURG NEUROL,LUBBOCK,TX 79430, USA. NR 31 TC 42 Z9 43 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 1994 VL 51 IS 8 BP 757 EP 766 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA PB130 UT WOS:A1994PB13000007 PM 8042923 ER PT J AU HENSON, DE HUTTER, RVP FARROW, GM BOSTWICK, DG HAMMOND, EM AYALA, AG GAETA, JF MOSTOFI, FK SOBIN, LH YAGODA, A HANKS, G LEE, F PILEPICH, M MURPHY, GP WHITMORE, W GARNETT, J DROLLER, MJ SMART, CR BOWMAN, HE GORSTEIN, F NIELSEN, ML SCULLY, RE TAYLOR, DG AF HENSON, DE HUTTER, RVP FARROW, GM BOSTWICK, DG HAMMOND, EM AYALA, AG GAETA, JF MOSTOFI, FK SOBIN, LH YAGODA, A HANKS, G LEE, F PILEPICH, M MURPHY, GP WHITMORE, W GARNETT, J DROLLER, MJ SMART, CR BOWMAN, HE GORSTEIN, F NIELSEN, ML SCULLY, RE TAYLOR, DG TI PRACTICE PROTOCOL FOR THE EXAMINATION OF SPECIMENS REMOVED FROM PATIENTS WITH CARCINOMA OF THE PROSTATE-GLAND - A PUBLICATION OF THE CANCER-COMMITTEE, COLLEGE-OF-AMERICAN-PATHOLOGISTS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID LYMPH-NODE METASTASIS; INTRAEPITHELIAL NEOPLASIA; RADICAL PROSTATECTOMIES; INCIDENTAL CARCINOMA; CYTOLOGICAL GRADE; DNA PLOIDY; PROGNOSIS; ADENOCARCINOMA; STAGE; INVOLVEMENT C1 ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ 07039. MAYO CLIN & MAYO FDN,DEPT PATHOL,ROCHESTER,MN 55905. RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EPN BLDG,ROOM 305,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 97 Z9 97 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1994 VL 118 IS 8 BP 779 EP 783 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA PB262 UT WOS:A1994PB26200007 PM 8060223 ER PT J AU OLEARY, TJ STETLERSTEVENSON, M AF OLEARY, TJ STETLERSTEVENSON, M TI DIAGNOSIS OF T(1418) BY POLYMERASE CHAIN-REACTION - THE NATURAL EVOLUTION OF A LABORATORY TEST SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID T(14-18) CHROMOSOMAL TRANSLOCATION; STAGE FOLLICULAR LYMPHOMA; NON-HODGKINS-LYMPHOMA; BCL-2 GENE; BONE-MARROW; DISEASE; CELLS; REARRANGEMENTS; AMPLIFICATION; REMISSION C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP OLEARY, TJ (reprint author), ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306, USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1994 VL 118 IS 8 BP 789 EP 790 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA PB262 UT WOS:A1994PB26200009 PM 8060225 ER PT J AU GUINEE, DG FEUERSTEIN, I KOSS, MN TRAVIS, WD AF GUINEE, DG FEUERSTEIN, I KOSS, MN TRAVIS, WD TI PULMONARY LYMPHANGIOLEIOMYOMATOSIS - DIAGNOSIS BASED ON RESULTS OF TRANSBRONCHIAL BIOPSY AND IMMUNOHISTOCHEMICAL STUDIES AND CORRELATION WITH HIGH-RESOLUTION COMPUTED-TOMOGRAPHY FINDINGS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Note ID TUBEROUS SCLEROSIS; LYMPHANGIOMYOMATOSIS; CT AB The diagnosis of lymphangioleiomyomatosis was established in a 35-year-old woman with hemoptysis, mild cough, and dyspnea based on histologic review of results of a transbronchial biopsy correlated with high-resolution computed tomographic scan findings. A chest x-ray film revealed diffuse interstitial lung disease, and a high-resolution computed tomographic scan showed diffuse cystic changes throughout both lungs. The transbronchial biopsy specimen revealed cystic changes and a patchy, sometimes nodular proliferation of smooth muscle that focally expanded the interstitium suggestive of lymphangioleiomyomatosis. The smooth-muscle nature of the cells was confirmed by positive immunohistochemical stains for actin and desmin; positive staining for HMB-45 was also observed. Although the diagnosis of lymphangioleiomyomatosis usually requires an open lung biopsy, this case shows that rarely, in the appropriate clinical setting, the diagnosis may be rendered based on results of a transbronchial biopsy in conjunction with findings from ancillary immunohistochemical studies and high-resolution computed tomography. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. RP GUINEE, DG (reprint author), ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306, USA. NR 19 TC 24 Z9 24 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1994 VL 118 IS 8 BP 846 EP 849 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA PB262 UT WOS:A1994PB26200026 PM 8060240 ER PT J AU BROWN, AK SLEEPER, LA MILLER, ST PEGELOW, CH GILL, FM WACLAWIW, MA AF BROWN, AK SLEEPER, LA MILLER, ST PEGELOW, CH GILL, FM WACLAWIW, MA TI REFERENCE VALUES AND HEMATOLOGIC CHANGES FROM BIRTH TO 5 YEARS IN PATIENTS WITH SICKLE-CELL-DISEASE SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID FETAL-HEMOGLOBIN; CLINICAL EXPRESSION; ALPHA-THALASSEMIA; GLOBIN GENE; ANEMIA; DISORDERS; DYSFUNCTION; MORTALITY; SURVIVAL; NEWBORN AB Objective: To examine hematologic changes from birth to 5 years of age and establish hematologic reference values for infants and children with sickle cell disease. Research Design: Prospective natural history study. Setting: Nineteen pediatric sickle cell centers across the United States. Patients: Six hundred ninety-four infants with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and sickle-beta-thalassemia) who were enrolled in the Cooperative Study of Sickle Cell Disease at younger than 6 months of age. Median follow-up time through 5 years of age was 4.1 years. Measurements and Results: We present longitudinal analyses of total hemoglobin concentration, percent fetal hemoglobin values, mean corpuscular volumes, total bilirubin concentration, and red blood cell (RBC), ''pocked'' RBC, white blood cell, platelet, and reticulocyte counts. Anemia was apparent by 10 weeks of life in infants with sickle cell anemia (SS infants). This anemia was associated with a rising reticulocyte count consistent with a hemolytic process. The reticulocyte count of SS infants increased steadily, exceeding 12% at 5 years of age. The fetal hemoglobin concentration of SS infants declined more slowly than that of infants with sickle cell hemo globin C disease (SC infants). Pocked RBC counts rose sharply after 6 months of age, and by 1 year, 28% of SS infants had abnormal counts, above 3.5%, indicating poor splenic function. At 3 years of age, 78% of SS patients and 32% of SC patients had abnormal pocked RBC counts. The SS patients with concurrent alpha-thalassemia had, after 6 months of age and throughout early childhood, a slightly higher mean total hemoglobin concentration and lower mean pocked RBC and reticulocyte counts than SS patients without alpha-thalassemia. The hematologic profile of SC infants more closely resembled that of normal black infants, but there was mild anemia (10.5 g/dL) and slightly elevated mean values for reticulocytes (3%) and fetal hemoglobin (3%) during early childhood. C1 SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV MIAMI,DIV PEDIAT HEMATOL,MIAMI,FL 33152. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 31 TC 60 Z9 60 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 1994 VL 148 IS 8 BP 796 EP 804 PG 9 WC Pediatrics SC Pediatrics GA PB264 UT WOS:A1994PB26400004 PM 7519102 ER PT J AU JACOBSSON, LTH HANSON, RL KNOWLER, WC PILLEMER, S PETTITT, DJ MCCANCE, DR BENNETT, PH AF JACOBSSON, LTH HANSON, RL KNOWLER, WC PILLEMER, S PETTITT, DJ MCCANCE, DR BENNETT, PH TI DECREASING INCIDENCE AND PREVALENCE OF RHEUMATOID-ARTHRITIS IN PIMA-INDIANS OVER A 25-YEAR PERIOD SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SHARED EPITOPE HYPOTHESIS; YAKIMA INDIANS; HLA; MORTALITY; WOMEN; PILL; RISK AB Objective. To evaluate temporal trends in the incidence of rheumatoid arthritis (RA). Methods. Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965-1990. Results. Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (P-trend = 0.225), and by 57% in women (P-trend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (P-trend = 0.63) and by 40% in women (P-trend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990. Conclusion. The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded. C1 NIAMSD,PHOENIX,AZ. NIAMSD,BETHESDA,MD 20892. NIDDKD,PHOENIX,AZ. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 35 TC 76 Z9 77 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1994 VL 37 IS 8 BP 1158 EP 1165 DI 10.1002/art.1780370808 PG 8 WC Rheumatology SC Rheumatology GA PA916 UT WOS:A1994PA91600007 PM 8053953 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD TI SERUM LEVELS OF INSULIN-LIKE GROWTH-FACTOR-1 IN SUBJECTS WITH OSTEOARTHRITIS OF THE KNEE - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BOVINE ARTICULAR-CARTILAGE; FACTOR-I; CHONDROCYTES; PROTEOGLYCANS; HORMONE; METABOLISM; EXPLANTS; CULTURE; PLATE; AGE AB Objective. To examine the relationship between serum levels of insulin-like growth factor 1 (IGF-1) and osteoarthritis (OA) of the knee. Methods. Serum IGF-1 levels were compared in 162 male and 101 female subjects age greater than or equal to 20 stratified by presence of radiographic changes of OA of the knee. Results. Mean serum IGF-1 levels were significantly lower in subjects with knee OA; however, after adjustment for age-related changes in IGF-1 levels, these differences were no longer significant. Conclusion. These data fail to support the hypothesis that serum IGF-1 levels are reduced in subjects with OA of the knee independent of the known age-related changes in these levels. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP HOCHBERG, MC (reprint author), UNIV MARYLAND,SCH MED,PROFESS BLDG,419 W REDWOOD ST,SUITE 620,BALTIMORE,MD 21201, USA. NR 27 TC 36 Z9 36 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1994 VL 37 IS 8 BP 1177 EP 1180 DI 10.1002/art.1780370811 PG 4 WC Rheumatology SC Rheumatology GA PA916 UT WOS:A1994PA91600010 PM 8053956 ER PT J AU RUBIN, LA AMOS, CI WADE, JA MARTIN, JR BALE, SJ LITTLE, AH GLADMAN, DD BONNEY, GE RUBENSTEIN, JD SIMINOVITCH, KA AF RUBIN, LA AMOS, CI WADE, JA MARTIN, JR BALE, SJ LITTLE, AH GLADMAN, DD BONNEY, GE RUBENSTEIN, JD SIMINOVITCH, KA TI INVESTIGATING THE GENETIC-BASIS FOR ANKYLOSING-SPONDYLITIS - LINKAGE STUDIES WITH THE MAJOR HISTOCOMPATIBILITY COMPLEX REGION SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOD SCORES; HLA-B27; ANTIGEN; ASSOCIATION; MOLECULES; SUSCEPTIBILITY; INHERITANCE; HAPLOTYPES; DISEASE; FAMILY AB Objective. To assess the hypothesis that B27 or a gene(s) in close proximity (e.g., within or near the major histocompatibility complex [MHC]) represents a disease-causing ankylosing spondylitis (AS) gene, and therefore contributes directly to the pathogenesis of this disorder. Methods. MHC haplotypes were determined by both serologic and molecular analyses in 15 multiple-case AS families from Toronto and Newfoundland. Segregation of MHC haplotypes with AS within these families was examined by linkage and identity-by-descent analyses. Attributable risk estimates for various genetic markers and for sex were calculated. Results. Linkage analyses established significant linkage between AS and the MBC, the maximal logarithm of odds (LOD) score being 3.48 at a recombination frequency (Theta) of 0.05. In a second analysis in which the population association of the MWC gene HLA-B27 with AS was taken into account, the maximal LOD score was 7.5 at Theta = 0.05. Identity-by-descent analyses showed a significant departure from random segregation among affected avuncular (P < 0.05) and cousin (P < 0.01) pairs. The presence of HLA-B40 in HLA-B27 positive individuals increased the risk for disease more than 3-fold, confirming previous reports. Disease susceptibility modeling suggested an autosomal dominant pattern of inheritance, with penetrance of approximately 20%. Conclusion. These data provide the first conclusive demonstration of linkage between the MHC region and AS, and confirm that genes within this region contribute directly to the genetic susceptibility for AS. C1 UNIV TORONTO,TORONTO,ON,CANADA. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. TORONTO HOSP,TORONTO M5T 2S8,ON,CANADA. MEM UNIV NEWFOUNDLAND,ST JOHNS,NF,CANADA. NIAMS,BETHESDA,MD. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RI Siminovitch, Katherine/K-1475-2013 NR 45 TC 87 Z9 92 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1994 VL 37 IS 8 BP 1212 EP 1220 DI 10.1002/art.1780370816 PG 9 WC Rheumatology SC Rheumatology GA PA916 UT WOS:A1994PA91600015 PM 8053961 ER PT J AU BARTENS, W RADER, DJ TALLEY, G BREWER, HB AF BARTENS, W RADER, DJ TALLEY, G BREWER, HB TI DECREASED PLASMA-LEVELS OF LIPOPROTEIN(A) IN PATIENTS WITH HYPERTRIGLYCERIDEMIA SO ATHEROSCLEROSIS LA English DT Article DE APOLIPOPROTEIN (A); ATHEROSCLEROSIS; CHOLESTEROL; HYPERTRIGLYCERIDEMIA ID LP(A) GLYCOPROTEIN PHENOTYPES; B-CONTAINING LIPOPROTEINS; CORONARY HEART-DISEASE; APOLIPOPROTEIN-B; FAMILIAL HYPERCHOLESTEROLEMIA; RECEPTOR GENE; DENSITY; ATHEROSCLEROSIS; HETEROGENEITY; ASSOCIATION AB Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors modulating plasma Lp(a) concentrations are poorly understood. To investigate the possible interaction of Lp(a) with triglycerides, we determined the apo(a) phenotype, Lp(a) concentration, and distribution of Lp(a) in a group of patients with triglycerides > 400 mg/dl (n = 60) compared with a control group (n = 128). Lp(a) concentrations were significantly lower in hypertriglyceridemic patients (mean +/- S.E., 13 +/- 4 mg/dl; median, 6 mg/dl; 25/75 percentile, 2-13 mg/dl) as compared with the controls (mean, 22 +/- 2 mg/dl; median, 10 mg/dl; 25/75 percentile, 7-30 mg/dl). Plasma Lp(a) concentrations in the hypertriglyceridemic patients correlated negatively with triglyceride levels (r = -0.69, P = 0.03). The difference in Lp(a) levels between patients and controls was maintained when subjects were stratified by apo(a) phenotype and type of hyperlipidemia. After subdividing the hypertriglyceridemic patients into one group with apo(a) isoforms less than or equal to S2 and one group with apo(a) isoforms greater than or equal to S3, we found that the differences in plasma Lp(a) concentrations between patients and controls were more pronounced in the group with the lower molecular weight apo(a) isoforms. These data indicate that hypertriglyceridemia is associated with lower plasma Lp(a) concentrations and suggest that increased levels of triglyceride-rich lipoproteins may influence the metabolism of Lp(a). C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 38 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 AUG PY 1994 VL 108 IS 2 BP 149 EP 157 DI 10.1016/0021-9150(94)90109-0 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PD601 UT WOS:A1994PD60100004 PM 7980714 ER PT J AU BOINSKI, S MORAES, E KLEIMAN, DG DIETZ, JM BAKER, AJ AF BOINSKI, S MORAES, E KLEIMAN, DG DIETZ, JM BAKER, AJ TI INTRAGROUP VOCAL BEHAVIOR IN WILD GOLDEN LION TAMARINS, LEONTOPITHECUS-ROSALIA - HONEST COMMUNICATION OF INDIVIDUAL ACTIVITY SO BEHAVIOUR LA English DT Article ID FOOD-ELICITED VOCALIZATIONS; FEMALE SQUIRREL-MONKEYS; DESIGN-FEATURES; CALLS; FIELD; COORDINATION; REPERTOIRE; HANDICAP; CONTEXT; CUES AB We report the first field study of the intra-group vocal behaviour of golden lion tamarins (Leontopithecus rosalia). We present the contexts in which the five predominant intra-group vocalizations (cluck, whine, wah-wah, tsick, and trill) were emitted, including the behavioural responses elicited from other group members, for 25 adult and subadult golden lion tamarins in five wild groups. No age (subadult versus adult), sex, age of nearest neighbour, and few group differences in call usage were identified. Each intra-group vocalization was associated with a specific ecological context; few vocalizations were produced during dyadic social interactions. Clucks predominated during foraging. Clucks were also relatively more common when the group was travelling, but the focal tamarin was stationary (not locomoting). Whines were more likely when the animal was in a travelling group, stationary, not foraging or locomoting, and when the nearest neighbour was further away than five m. Trills were almost exclusively emitted when a tamarin was leaping, and were a strong predictor of foraging upon landing. No change in the mean distance to the nearest neighbour was detected subsequent to the production of a cluck, whine or trill, although juveniles immediately approached to obtain food items when tsick calls were uttered. Wah-wahs were more likely when the caller was on the group periphery and may function in the initiation and leading of group movement; a stationary group usually moved in the trajectory predicted by the wah-wahing tamarin's location relative to the group center. These findings suggest that the intra-group vocalizations of this small arboreal primate provide honest information regarding numerous aspects of the caller's immediate location, activity and intent. Directly and indirectly these vocalizations may function to facilitate group cohesion and the coordination of group movement by enhancing cooperation among group members. C1 UNIV FLORIDA,DIV COMPARAT MED,GAINESVILLE,FL 32611. NIH,CTR ANIM,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837. BIOL RESERVE POCO ANTAS,SILVA JARDIM,RJ,BRAZIL. SMITHSONIAN INST,NATL ZOOL PK,DEPT ZOOL RES,WASHINGTON,DC 20008. UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. PHILADELPHIA ZOOL GARDENS,PHILADELPHIA,PA 19104. RP BOINSKI, S (reprint author), UNIV FLORIDA,DEPT ANTHROPOL,1350 TURLINGTON,GAINESVILLE,FL 32611, USA. NR 56 TC 23 Z9 23 U1 1 U2 28 PU E J BRILL PI LEIDEN PA PO BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD AUG PY 1994 VL 130 BP 53 EP 75 DI 10.1163/156853994X00145 PN 1-2 PG 23 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA PR385 UT WOS:A1994PR38500005 ER PT J AU ZHANGKECK, ZY SRIVASTAVA, M KOZAK, CA CAOHUY, H SHIRVAN, A BURNS, AL POLLARD, HB AF ZHANGKECK, ZY SRIVASTAVA, M KOZAK, CA CAOHUY, H SHIRVAN, A BURNS, AL POLLARD, HB TI GENOMIC ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF THE MOUSE SYNEXIN GENE SO BIOCHEMICAL JOURNAL LA English DT Article ID UPSTREAM ACTIVATION SITE; CALCIUM-CHANNEL ACTIVITY; EPIDERMAL GROWTH-FACTOR; MEMBRANE-FUSION; MESSENGER-RNA; ANNEXIN-VII; TRANSCRIPTION FACTOR; CHROMAFFIN GRANULES; CDNA SEQUENCE; GCN4 PROTEIN AB We have isolated and characterized the gene encoding mouse synexin, which consists of 14 exons and spans approximately 30 kbp of genomic DNA. The protein's unique N-terminal domain is encoded by six exons, and the C-terminal tetrad repeat, the site of the membrane-fusion and ion-channel domain, is encoded by seven exons. The first exon encodes the 5'-untranslated region. Analysis of synexin-gene expression in different mouse tissues shows that mRNA with exon 6 is only present in brain, heart and skeletal muscle, mRNA lacking exon 6 is expressed in all tissues we have examined. The initiation site for transcription was determined by primer-extension analysis and S1 nuclease mapping. Sequence analysis of the 1.3 kb 5'-flanking region revealed that the promoter has a TATA box located at position -25 and a number of potential promoter and regulatory elements. A CCAAT motif was not observed but CCATT is located in an appropriate position for the CCAAT motif upstream from the transcription-initiation start site. In addition, the 5'-flanking region contains two sets of palindromic sequences. Finally, we have determined that the functional synexin gene (Anx7) is located on mouse chromosome 14 and that a pseudogene (Anx7-ps1) is located on chromosome 10. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 56 TC 9 Z9 9 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 1994 VL 301 BP 835 EP 845 PN 3 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PB311 UT WOS:A1994PB31100029 PM 8053909 ER PT J AU SIMPSON, IA VANNUCCI, SJ MAHER, F AF SIMPSON, IA VANNUCCI, SJ MAHER, F TI GLUCOSE TRANSPORTERS IN MAMMALIAN BRAIN SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 650th Meeting of the Biochemical-Society CY APR 12-14, 1994 CL UNIV WALES, CARDIFF, WALES SP BIOCHEM SOC HO UNIV WALES ID RAT-BRAIN; GENE-EXPRESSION; INSITU HYBRIDIZATION; PRIMARY CULTURES; XENOPUS OOCYTES; SMALL-INTESTINE; GLIAL-CELLS; BARRIER; GLUT3; PROTEIN RP SIMPSON, IA (reprint author), NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892, USA. NR 43 TC 23 Z9 23 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1994 VL 22 IS 3 BP 671 EP 675 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE775 UT WOS:A1994PE77500027 PM 7821661 ER PT J AU RUSH, ME RINZEL, J AF RUSH, ME RINZEL, J TI ANALYSIS OF BURSTING IN A THALAMIC NEURON MODEL SO BIOLOGICAL CYBERNETICS LA English DT Article ID THALAMOCORTICAL RELAY NEURONS; LATERAL GENICULATE-NUCLEUS; GUINEA-PIG; CALCIUM CURRENTS; IONIC CURRENTS; ELECTROPHYSIOLOGICAL PROPERTIES; POTASSIUM CURRENT; OSCILLATIONS; TRANSIENT; INACTIVATION AB We extend a quantitative model for low-voltage, slow-wave excitability based on the T-type calcium current (Wang et al. 1991) by juxtaposing it with a Hodgkin-Huxley-like model for fast sodium spiking in the high voltage regime to account for the distinct firing modes of thalamic neurons. We employ bifurcation analysis to illustrate the stimulus-response behavior of the full model under both voltage regimes. The model neuron shows continuous sodium spiking when depolarized sufficiently from rest. Depending on the parameters of calcium current inactivation, there are two types of low-voltage responses to a hyperpolarizing current step: a single rebound low threshold spike (LTS) upon release of the step and periodic LTSs. Bursting is seen as sodium spikes ride the LTS crest. In both cases, we analyze the LTS burst response by projecting its trajectory into a fast/slow phase plane. We also use phase plane methods to show that a potassium A-current shifts the threshold for sodium spikes, reducing the number of fast sodium spikes in an LTS burst. It can also annihilate periodic bursting. We extend the previous work of Rose and Hindmarsh (1989a-c) for a thalamic neuron and propose a simpler model for thalamic activity. We consider burst modulation by using a neuromodulator-dependent potassium leakage conductance as a control parameter. These results correspond with experiments showing that the application of certain neurotransmitters can switch firing modes. C1 UNIV MARYLAND,DEPT MATH APPL,COLLEGE PK,MD 20742. NIDDK,MATH RES BRANCH,BETHESDA,MD 20892. NR 37 TC 47 Z9 49 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD AUG PY 1994 VL 71 IS 4 BP 281 EP 291 DI 10.1007/BF00239616 PG 11 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA PE407 UT WOS:A1994PE40700001 PM 7948220 ER PT J AU RUMSEY, JM ANDREASON, P ZAMETKIN, AJ KING, AC HAMBURGER, SD AQUINO, T HANAHAN, AP PIKUS, A COHEN, RM AF RUMSEY, JM ANDREASON, P ZAMETKIN, AJ KING, AC HAMBURGER, SD AQUINO, T HANAHAN, AP PIKUS, A COHEN, RM TI RIGHT FRONTOTEMPORAL ACTIVATION BY TONAL MEMORY IN DYSLEXIA, AN O-15 PET STUDY SO BIOLOGICAL PSYCHIATRY LA English DT Article DE DYSLEXIA; CEREBRAL BLOODFLOW; POSITRON EMISSION TOMOGRAPHY; COGNITIVE ACTIVATION; TONAL MEMORY ID HUMAN CEREBRAL METABOLISM; DEVELOPMENTAL DYSLEXIA; BRAIN MORPHOLOGY; LANGUAGE; COORDINATION; STIMULATION AB A prior study documented the failure of dyslexic men to activate left temporoparietal cortex during phonologic processing. Because of reports of an anomalous right planum temporale in developmental dyslexia, the functional implications of which are unknown, this study examined the ability of dyslexics to activate right temporal cortex. Regional cerebral blood flow was measured in 15 right-handed dyslexic men during rest and during a tonal memory task expected to activate right-sided cortex in controls. A matched control sample (n = 18) showed significant activation of several right frontotemporal regions as well as of left temporal cortex. In contrast, severely dyslexic men activated fewer right frontotemporal regions, while making many more errors than controls, but showed normal activation of left mid to anterior temporal cortex. These results support hypothesized underlying deficits in rapid temporal processing and possible involvement of right (in addition to left) temporal cortex in severe dyslexia. C1 NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. NIDCD,HEARING SECT,CLIN AUDIOL BRANCH,BETHESDA,MD. RP RUMSEY, JM (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. NR 33 TC 23 Z9 23 U1 1 U2 1 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 AUG 1 PY 1994 VL 36 IS 3 BP 171 EP 180 DI 10.1016/0006-3223(94)91222-X PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PB801 UT WOS:A1994PB80100004 PM 7948454 ER PT J AU CACHAU, RE AF CACHAU, RE TI MOLECULAR-DYNAMICS SIMULATIONS OF WATER USING A FLOATING POLYNOMIAL FORCE-FIELD AND AN INTERPOLATING ELECTROSTATIC-FIELD REPRESENTATION SO BIOPHYSICAL CHEMISTRY LA English DT Article DE MOLECULAR DYNAMICS; WATER; FLOATING POLYNOMIAL FORCE FIELD; INTERPOLATING ELECTROSTATIC FIELD REPRESENTATION ID LIQUID WATER; POTENTIAL FUNCTIONS; PROTEIN DYNAMICS; ENERGY; ASSOCIATIONS; MODELS; ATOMS AB The ability to accurately describe the force field of a molecule is of great importance in spectroscopic and drug design studies. However, the fitting of accurate potential energy functions has proved to be a highly complex task. The description through a simple generic formula of all conformations of a molecule has proved to be a seldom reliable procedure, while more complex representations are increasingly difficult to fit, slower to compute, and difficult to program. In this work, alternative procedures are explored: (1) the intramolecular force fields are expanded in a floating polynomial representation; (2) a fast treatment for the non-bonded interactions is applied. The advantage of these treatments is in their ability to describe highly accurate representations of molecules in a very efficient manner. The main difficulty is a heavy trade off in computer memory usage. Some of the more frequently used force fields for water, and a first principle force field are used as a test of these techniques. RP CACHAU, RE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702, USA. NR 34 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD AUG PY 1994 VL 51 IS 2-3 BP 217 EP 233 DI 10.1016/0301-4622(94)00043-3 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA PA335 UT WOS:A1994PA33500009 PM 7919033 ER PT J AU LEE, B AF LEE, B TI RELATION BETWEEN VOLUME CORRECTION AND THE STANDARD STATE SO BIOPHYSICAL CHEMISTRY LA English DT Article DE VOLUME CORRECTION; STANDARD STATE; HYDROPHOBICITY ID FREE-ENERGIES; SOLUTES; WATER AB The suggestion by Sharp et al. (Biochemistry 30 (1991) 9686) that a volume correction should be made to the standard chemical potential of a non-polar solute molecule in water is examined by re-deriving their results using an exact statistical mechanical procedure and comparing them with those of a couple of other similar schemes. It is shown that their suggestion is equivalent to choosing a standard state based on the ideal gas behavior. RP LEE, B (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37,RM 4B15,BETHESDA,MD 20892, USA. NR 15 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD AUG PY 1994 VL 51 IS 2-3 BP 263 EP 269 DI 10.1016/0301-4622(94)00047-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA PA335 UT WOS:A1994PA33500013 PM 7919037 ER PT J AU LEE, B AF LEE, B TI ENTHALPY-ENTROPY COMPENSATION IN THE THERMODYNAMICS OF HYDROPHOBICITY SO BIOPHYSICAL CHEMISTRY LA English DT Article DE ENTHALPY; ENTROPY; COMPENSATION; HYDROPHOBIC; THERMODYNAMIC ID SOLVENT; WATER; SOLUBILITY; MOLECULES AB Using Widom's potential distribution theory (J. Chem. Phys. 39 (1963) 2808; J. Phys. Chem. 86 (1982) 869), a general and a special theorems are derived, by means of which one can judge whether a particular sub-process of an overall process will produce compensating changes in enthalpy and entropy. The enthalpy-entropy compensation phenomena that are observed in the transfer process of a hydrophobic molecule from a non-aqueous phase to water are examined in the light of these theorems. It is concluded that most sub-processes involved in the hydrophobic transfer process are compensating except one, that of inserting a cavity corresponding to the solute molecule in the liquid. The reason that this process is non-compensating, and therefore most responsible for the hydrophobicity, is traced to the hard core overlap between solvent and the solute molecules. RP LEE, B (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37,RM 4B15,BETHESDA,MD 20892, USA. NR 22 TC 155 Z9 155 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD AUG PY 1994 VL 51 IS 2-3 BP 271 EP 278 DI 10.1016/0301-4622(94)00048-4 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA PA335 UT WOS:A1994PA33500014 PM 7919038 ER PT J AU MADAN, B LEE, B AF MADAN, B LEE, B TI ROLE OF HYDROGEN-BONDS IN HYDROPHOBICITY - THE FREE-ENERGY OF CAVITY FORMATION IN WATER MODELS WITH AND WITHOUT THE HYDROGEN-BONDS SO BIOPHYSICAL CHEMISTRY LA English DT Article DE HYDROPHOBICITY; WATER STRUCTURE; CAVITY FREE ENERGY; SIMULATION ID MOLECULAR-DYNAMICS; NONPOLAR SOLUTES; MONTE-CARLO; SIZE DEPENDENCE; LIQUID WATER; HYDRATION; SOLVENT; SIMULATION; SOLUBILITY; SOLVATION AB The free energies of cavity formation in water with and without hydrogen bonding potential were computed from the results of a set of Monte Carlo simulation calculations on pure liquid TIP4P water model and on the same model but with the electrostatic charges turned off (Lennard-Jones liquid). The free energies of cavity formation in the Lennard-Jones liquids are higher than or approximately equal to those in TIP4P water, depending, respectively, on whether the Lennard-Jones size parameter sigma is set equal to 3.15 Angstrom which is the value of sigma for TIP4P water, or to 2.8 Angstrom which is the commonly assumed value for the oxygen-oxygen distance between two hydrogen-bonded water molecules. This result indicates that changes in the hydrogen-bonded structure of water and/or in the orientational degree of freedom of water are not essential features in the production of the large free energy change upon cavity formation. C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 37 TC 111 Z9 111 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD AUG PY 1994 VL 51 IS 2-3 BP 279 EP 289 DI 10.1016/0301-4622(94)00049-2 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA PA335 UT WOS:A1994PA33500015 PM 7919039 ER PT J AU RASHIN, AA YOUNG, L TOPOL, IA AF RASHIN, AA YOUNG, L TOPOL, IA TI QUANTITATIVE-EVALUATION OF HYDRATION THERMODYNAMICS WITH A CONTINUUM MODEL SO BIOPHYSICAL CHEMISTRY LA English DT Article DE HYDRATION; CONTINUUM MODEL; THERMODYNAMICS ID DENSITY FUNCTIONAL CALCULATIONS; PROTEIN-FOLDING THERMODYNAMICS; BOUNDARY ELEMENT METHOD; ELECTROSTATICS; MOLECULES; ENERGIES; CHARGES; MACROMOLECULES; STABILITY; ENTROPIES AB We attempt to analyze whether experimental entropies, enthalpies and free energies of hydration of small uncharged molecules can be quantitatively rationalized with a continuum model including a classical reaction field formalism. We find that a simple proportionality to accessible surface with five different atom types allows satisfactory (within 1-1.5 kcal/mol) reproduction of hydration entropies (T Delta S) of over 40 solutes. The agreement with experiment can possibly be improved if proximity effects and configurational contributions to transfer entropies are taken into account. In calculations of hydration enthalpies a reasonable agreement with experimental data can be obtained only when solute polarizability is taken into account. Electrostatic contributions to calculated hydration enthalpies exhibit strong dependencies on both the magnitude and the direction of molecular dipole moments. We demonstrate that for 20 molecules with experimentally measured vacuum dipole moments density functional calculations with DZVPD basis set including diffuse functions on d-orbitals allows prediction of experimental dipole moments within 0.1 D. At a fixed direction of the molecular dipole moment, mu, the electrostatic component of hydration enthalpy varies as mu(2). Thus an uncertainty of 0.1 D corresponds to uncertainties of 0.5-0.7 kcal/mol in hydration enthalpies of most small dipolar solutes. A 30 degrees change in the direction of the molecular dipole together with the corresponding change in the quadrupole moment can result in a change of hydration enthalpy of 3 kcal/mol. Changes in the quadrupole moment alone can result in hydration enthalpy changes of over 1 kcal/mol. Representations of multipole expansions by point charges on nuclei fitted to molecular electrostatic potentials cannot accurately reproduce all these factors. Use of such point charges in calculations of hydration enthalpies predictably leads to discrepancies with experiment of approximate to 3 kcal/mol for some solutes. However, errors in hydration enthalpies and hydration entropies are usually compensating leading in most cases to agreement between calculated and experimental free energies of hydration within 1.5 kcal/mol. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702. RP RASHIN, AA (reprint author), BIOCHEMCOMP INC,543 SAGAMORE AVE,TEANECK,NJ 07666, USA. NR 39 TC 49 Z9 50 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD AUG PY 1994 VL 51 IS 2-3 BP 359 EP 374 DI 10.1016/0301-4622(94)00058-1 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA PA335 UT WOS:A1994PA33500021 PM 7919043 ER PT J AU POLLARD, JR ARISPE, N ROJAS, E POLLARD, HB AF POLLARD, JR ARISPE, N ROJAS, E POLLARD, HB TI A GEOMETRIC SEQUENCE THAT ACCURATELY, DESCRIBES ALLOWED MULTIPLE CONDUCTANCE LEVELS OF ION CHANNELS - THE 3-HALVES (3/2)-RULE SO BIOPHYSICAL JOURNAL LA English DT Article ID FORMS CALCIUM CHANNELS; GUINEA-PIG HEART; BILAYER-MEMBRANES; CHLORIDE CHANNELS; UNIT CONDUCTANCE; HUMAN PLATELETS; SODIUM-CHANNEL; ANION CHANNEL; STATES; NEURONS AB Ion channels can express multiple conductance levels that are not integer multiples of some unitary conductance, and that interconvert among one another. We report here that for 26 different types of multiple conductance channels, all allowed conductance levels can be calculated accurately using the geometric sequence g(n) = g(o)(3/2)(n), where g(n) is a conductance level and n is an integer greater than or equal to 0. We refer to this relationship as the ''3/2 Rule,'' because the value of any term in the sequence of conductances (g(n)) can be calculated as 3/2 times the value of the preceeding term (g(n-1)). The experimentally determined average Value for ''3/2'' is 1.491 +/- 0.095 (sample size = 37, average +/- SD). We also verify the choice of a 3/2 ratio on the basis of error analysis over the range of ratio values between 1.1 and 2.0. In an independent analysis using Marquardt's aligorithm, we further verified the 3/2 ratio and the assignment of specific conductances to specific terms in the geometric sequence. Thus, irrespective of the open time probability, the allowed conductance levels of these channels can be described accurately to within similar to 6%. We anticipate that the ''3/2 Rule'' will simplify description of multiple conductance channels in a wide variety of biological systems and provide an organizing principle for channel heterogeneity and differential effects of channel blockers. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 49 TC 11 Z9 11 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1994 VL 67 IS 2 BP 647 EP 655 PG 9 WC Biophysics SC Biophysics GA NY823 UT WOS:A1994NY82300017 PM 7524712 ER PT J AU SHAPIRO, SG WILLIS, B AF SHAPIRO, SG WILLIS, B TI A PLASMID VECTOR, PTG-LINK, FOR CONVENIENT ASSEMBLY OF DNA FRAGMENTS FOR TRANSGENIC ANIMAL PRODUCTION SO BIOTECHNIQUES LA English DT Note RP SHAPIRO, SG (reprint author), NIDDKD,BIOL CHEM LAB,BLDG 10,ROOM 9N-3-7,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 1994 VL 17 IS 2 BP 254 EP 256 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA948 UT WOS:A1994PA94800010 PM 7980918 ER PT J AU GU, J STEPHENSON, CG IADAROLA, MJ AF GU, J STEPHENSON, CG IADAROLA, MJ TI RECOMBINANT PROTEINS ATTACHED TO A NICKEL-NTA COLUMN - USE IN AFFINITY PURIFICATION OF ANTIBODIES SO BIOTECHNIQUES LA English DT Note RP GU, J (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 90 Z9 91 U1 2 U2 9 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 1994 VL 17 IS 2 BP 257 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PA948 UT WOS:A1994PA94800011 PM 7980919 ER PT J AU SADLER, JE GRALNICK, HR AF SADLER, JE GRALNICK, HR TI A NEW CLASSIFICATION FOR VON-WILLEBRAND DISEASE - COMMENTARY SO BLOOD LA English DT Editorial Material ID MOLECULAR-WEIGHT MULTIMERS; VIII-VONWILLEBRAND-FACTOR; PLASMA; PLATELETS; DEFECT C1 WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOPHYS,ST LOUIS,MO 63110. WASHINGTON UNIV,JEWISH HOSP ST LOUIS,SCH MED,ST LOUIS,MO 63110. NIH,CTR CLIN,SERV HEMATOL,BETHESDA,MD 20892. RP SADLER, JE (reprint author), WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,660 S EUCLID,BOX 8022,ST LOUIS,MO 63110, USA. RI Sadler, Evan/D-8556-2011; OI Sadler, J. Evan/0000-0001-5705-469X NR 11 TC 80 Z9 83 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1994 VL 84 IS 3 BP 676 EP 679 PG 4 WC Hematology SC Hematology GA NZ250 UT WOS:A1994NZ25000002 PM 8043857 ER PT J AU BHATIA, K SPANGLER, G GAIDANO, G HAMDY, N DALLAFAVERA, R MAGRATH, L AF BHATIA, K SPANGLER, G GAIDANO, G HAMDY, N DALLAFAVERA, R MAGRATH, L TI MUTATIONS IN THE CODING REGION OF C-MYC OCCUR FREQUENTLY IN ACQUIRED IMMUNODEFICIENCY SYNDROME-ASSOCIATED LYMPHOMAS SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; BURKITT-LYMPHOMA; VIRUS; BINDING; PROTEIN; AIDS C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,DIV ONCOL,NEW YORK,NY. RP BHATIA, K (reprint author), NCI,LYMPHOMA BIOL SECT,BLDG 10-13C205,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-37295] NR 13 TC 67 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1994 VL 84 IS 3 BP 883 EP 888 PG 6 WC Hematology SC Hematology GA NZ250 UT WOS:A1994NZ25000029 PM 8043869 ER PT J AU VESOLE, DH BARLOGIE, B JAGANNATH, S CHESON, B TRICOT, G ALEXANIAN, R CROWLEY, J AF VESOLE, DH BARLOGIE, B JAGANNATH, S CHESON, B TRICOT, G ALEXANIAN, R CROWLEY, J TI HIGH-DOSE THERAPY FOR REFRACTORY MULTIPLE-MYELOMA - IMPROVED PROGNOSIS WITH BETTER SUPPORTIVE CARE AND DOUBLE TRANSPLANTS SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; INTENSIVE THERAPY; MELPHALAN C1 UNIV ARKANSAS MED SCI HOSP,DIV HEMATOL ONCOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,ARKANSAS CANC RES CTR,LITTLE ROCK,AR 77205. NCI,ROCKVILLE,MD. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. FU NCI NIH HHS [CA 55819] NR 23 TC 150 Z9 153 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1994 VL 84 IS 3 BP 950 EP 956 PG 7 WC Hematology SC Hematology GA NZ250 UT WOS:A1994NZ25000039 PM 7913845 ER PT J AU MIYAMURA, K BARRETT, AJ KODERA, Y SAITO, H AF MIYAMURA, K BARRETT, AJ KODERA, Y SAITO, H TI MINIMAL RESIDUAL DISEASE AFTER BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA AND IMPLICATIONS FOR GRAFT-VERSUS-LEUKEMIA EFFECT - A REVIEW OF RECENT RESULTS SO BONE MARROW TRANSPLANTATION LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; CHROMOSOME-POSITIVE CELLS; T-CELL; PHILADELPHIA-CHROMOSOME; MESSENGER-RNA; INTERFERON THERAPY; CHRONIC PHASE; HOST DISEASE AB Cure of leukemia by allogeneic BMT is achieved by the combined effect of the myeloablative preparative regimen and an allo-immune response of donor cells to residual leukemia termed the graft-versus-leukemia (GVL) effect. In the first year following BMT for CML, PCR used to detect the leukemia-specific BCR/ABL message frequently reveals subclinical levels of persisting leukemia. In a meta-analysis of reports on qualitative PCR findings after BMT for CML in 12 recently published series, we found that for unmanipulated BMT in chronic phase, PCR detection was not associated with a higher relapse risk and that most patients became PCR negative within 2 years post-BMT. In contrast, PCR detection of BCR/ABL transcripts was a more reliable predictor in recipients of T cell-depleted BMT and in those transplanted in accelerated or blastic phase of their disease. For accurate prediction of relapse, serial quantitative PCR is necessary. It could also be used to monitor efficacy of experimental treatments of relapse with interferon or donor lymphocyte transfusions. Furthermore, studies of the association of GVHD with PCR detection of BCR/ABL message may shed light on the relationship of GVL with minimal residual disease in CML. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NAGOYA FIRST HOSP,JAPANESE RED CROSS,DEPT INTERNAL MED,NAGOYA,AICHI,JAPAN. NAGOYA BONE MARROW TRANSPLANTAT GRP,NAGOYA,AICHI,JAPAN. RP MIYAMURA, K (reprint author), NAGOYA UNIV,SCH MED,DEPT INTERNAL MED 1,SHOWA KU,65 TSURUMAI,NAGOYA,AICHI 466,JAPAN. NR 64 TC 49 Z9 49 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 1994 VL 14 IS 2 BP 201 EP 209 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA PE172 UT WOS:A1994PE17200005 PM 7994233 ER PT J AU VARGHAKHADEM, F ISAACS, E MISHKIN, M AF VARGHAKHADEM, F ISAACS, E MISHKIN, M TI AGNOSIA, ALEXIA AND A REMARKABLE FORM OF AMNESIA IN AN ADOLESCENT BOY SO BRAIN LA English DT Article DE AGNOSIA; ALEXIA; AMNESIA; PEDIATRIC; AUTOMATIC WRITING ID CRANIAL IRRADIATION; BRAIN-TUMORS; MEMORY; CHILDHOOD; MEDULLOBLASTOMA; PERFORMANCE; LEUKEMIA; CHILDREN; DISORDER; IMAGERY AB Childhood cases of global anterograde amnesia, visual agnosia or alexia without agraphia, either alone or in any combination, are extremely rare. Here we report the case of a male adolescent, Neil (a pseudonym), who consequent to a pineal tumour began to exhibit all three disorders in the presence of normal verbal intelligence. The most surprising aspect of Neil's case, however, is his ability to retrieve postmorbid memories through the net of writing without being able to provide any oral account of the content of his written reports. His memory retrieval thus has some of the character of 'automatic writing'. This evidence pointing to possession of a dissociated form of episodic memory presents a new challenge to our understanding of the organization of memory and of the cerebral systems underlying it. C1 UNIV LONDON,INST CHILD HLTH,NEUROSCI UNIT,LONDON WC1N 1EH,ENGLAND. GREAT ORMOND ST HOSP CHILDREN NHS TRUST,DEPT PSYCHOL MED,LONDON,ENGLAND. NIMH,BETHESDA,MD 20892. RI Vargha-Khadem, Faraneh/C-2558-2008 FU Wellcome Trust NR 60 TC 16 Z9 16 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 1994 VL 117 BP 683 EP 703 DI 10.1093/brain/117.4.683 PN 4 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PQ948 UT WOS:A1994PQ94800005 PM 7922457 ER PT J AU DEUSCHL, G TORO, C VALLSSOLE, J ZEFFIRO, T ZEE, DS HALLETT, M AF DEUSCHL, G TORO, C VALLSSOLE, J ZEFFIRO, T ZEE, DS HALLETT, M TI SYMPTOMATIC AND ESSENTIAL PALATAL TREMOR .1. CLINICAL, PHYSIOLOGICAL AND MRI ANALYSIS SO BRAIN LA English DT Article DE PALATAL TREMOR; PALATAL MYOCLONUS; TREMOR; MRI; INFERIOR OLIVE ID OLIVARY HYPERTROPHY; INFERIOR OLIVE; PURKINJE-CELLS; MYOCLONUS; NEURONS; CAT; DISORDER; INVITRO; REFLEX; RAT AB Palatal tremor (brief rhythmic involuntary movements of the soft palate) apparently comprises two different nosological entities: essential palatal tremor (EPT) and symptomatic palatal tremor (SPT). The site of the abnormality in EPT is unknown, whereas SPT is believed to arise from a lesion of the brainstem or cerebellum (within the Guillain-Mollaret triangle). The clinical and physiological properties of these conditions were studied in four patients with EPT and six patients with SPT Patients with EPT had normal cerebellar function, but those with SPT had clinical signs of cerebellar dysfunction. The palatal movements were consistent with activation of the tenser veli palatini muscle in EPT and of the levator veli palatini muscle in SPT. During sleep, EPT stopped, whereas SPT continued with only slight variations in the tremor rate. The cycle of palatal tremor could not be reset by stimulation of trigeminal afferents in either EPT or SPT patients, and Valsalva's manoeuvre did not consistently affect the rhythm of the tremor in either group. The palatal tremor cycle exerted remote effects on the tonic electromyographic activity of the upper and lower extremities only in patients with SPT. These effects were present only on the side of the cerebellar signs (opposite the side with the enlarged inferior olive) in patients with a unilateral syndrome. Essential palatal tremor patients had only polysynaptic brain stem reflex abnormalities, whereas SPT patients had abnormalities of monosynaptic, oligosynaptic and polysynaptic brainstem reflexes. Magnetic resonance imaging showed no evidence of structural abnormalities in EPT patients, but SPT patients had a hyperdense signal of the ventral upper medulla (the region of the inferior olive) on T-2-weighted images. These observations support the hypothesis that EPT and SPT are two different diseases. In SPT cerebellar dysfunction ipsilateral to the palatal tremor may be due, in part, to abnormal function of the contralateral hypertrophic inferior olive. The proposed basis of SPT is a disturbance of electrotonic coupling between the cells of the inferior olive induced by a lesion of the dentato-olivary pathway. Similar mechanisms could be responsible for postural tremors in general. The pathophysiological basis of EPT remains unknown. C1 NINCDS, MED NEUROL BRANCH, HUMAN MOTOR CONTROL SECT, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV HOSP, DEPT NEUROL, BALTIMORE, MD 21205 USA. RI Deuschl, Gunther/A-7986-2010 NR 57 TC 140 Z9 142 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 1994 VL 117 BP 775 EP 788 DI 10.1093/brain/117.4.775 PN 4 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PQ948 UT WOS:A1994PQ94800013 PM 7922465 ER PT J AU PASCUALLEONE, A VALLSSOLE, J WASSERMANN, EM HALLETT, M AF PASCUALLEONE, A VALLSSOLE, J WASSERMANN, EM HALLETT, M TI RESPONSES TO RAPID-RATE TRANSCRANIAL MAGNETIC STIMULATION OF THE HUMAN MOTOR CORTEX SO BRAIN LA English DT Article DE RAPID-RATE TRANSCRANIAL MAGNETIC STIMULATION; MOTOR CORTEX; EPILEPSY; PHYSIOLOGY; ELECTROMYOGRAPHY (EMG) ID CORTICAL STIMULATION; HUMAN-BRAIN; INTACT MAN; SPREAD; EPILEPSY; MUSCLES; REPRESENTATIONS; EXCITABILITY; CONNECTIONS; MECHANISMS AB We applied trains of focal, rapid-rate transcranial magnetic stimulation (rTMS) to the motor cortex of 14 healthy volunteers with recording of the EMG from the contralateral abductor pollicis brevis, extensor carpi radialis, biceps brachii and deltoid muscles. Modulation of the amplitude of motor evoked potentials (MEPs) produced in the target muscle during rTMS showed a pattern of inhibitory and excitatory effects which depended on the rTMS frequency and intensity. With the magnetic coil situated over the optimal scalp position for activating the abductor pollicis brevis, rTMS led to spread of excitation, as evident from the induction of progressively larger MEPs in the other muscles. The number of pulses inducing this spread of excitation decreased with increasing rTMS frequency and intensity. Latency of the MEPs produced in the other muscles during the spread of excitation was significantly longer than that produced by single-pulse TMS applied to the optimal scalp positions for their activation. The difference in MEP latency could be explained by a delay in intracortical conduction along myelinated cortico-cortical pathways. Following rTMS, a 3-4 min period of increased excitability was demonstrated by an increase in the amplitude of MEPs produced in the target muscles by single-pulse TMS. Nevertheless, repeated rTMS trains applied 1 min apart led to similar modulation of the responses and to spread of excitation after approximately the same number of pulses. This suggests that the spread might be due to the breakdown of inhibitory connections or the recruitment of excitatory pathways, whereas the post-stimulation facilitation may be due to a transient increase in the efficacy of excitatory synapses. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BETHESDA,MD 20892. RI Pascual-Leone, Alvaro/G-6566-2011 NR 48 TC 718 Z9 739 U1 5 U2 35 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 1994 VL 117 BP 847 EP 858 DI 10.1093/brain/117.4.847 PN 4 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PQ948 UT WOS:A1994PQ94800018 PM 7922470 ER PT J AU KANNEL, WB HO, KL THOM, T AF KANNEL, WB HO, KL THOM, T TI CHANGING EPIDEMIOLOGIC FEATURES OF CARDIAC-FAILURE SO BRITISH HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; ISOSORBIDE DINITRATE; UNITED-STATES; FRAMINGHAM; MORTALITY; CARDIOMYOPATHY; HYDRALAZINE; VARIABLES; ENALAPRIL; SURVIVAL C1 BOSTON UNIV,SCH MED,EVANS MEM RES FDN,DEPT MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,DIV CARDIOVASC,HARVARD THORNDIKE LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. NR 22 TC 117 Z9 119 U1 1 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0769 J9 BRIT HEART J JI Br. Heart J. PD AUG PY 1994 VL 72 IS 2 SU S BP 3 EP 9 PG 7 WC Cardiac & Cardiovascular Systems; History & Philosophy Of Science SC Cardiovascular System & Cardiology; History & Philosophy of Science GA PB901 UT WOS:A1994PB90100002 ER PT J AU BENNETT, JM CATOVSKY, D DANIEL, MT FLANDRIN, G GALTON, DAG GRALNICK, H SULTAN, C COX, C AF BENNETT, JM CATOVSKY, D DANIEL, MT FLANDRIN, G GALTON, DAG GRALNICK, H SULTAN, C COX, C TI THE CHRONIC MYELOID LEUKEMIAS - GUIDELINES FOR DISTINGUISHING CHRONIC GRANULOCYTIC, ATYPICAL CHRONIC MYELOID, AND CHRONIC MYELOMONOCYTIC LEUKEMIA - PROPOSALS BY THE FRENCH-AMERICAN-BRITISH-COOPERATIVE-LEUKEMIA-GROUP SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CHRONIC MYELOID LEUKEMIAS; ATYPICAL CML; PHILADELPHIA-NEGATIVE CML; CMML ID CHRONIC MYELOGENOUS LEUKEMIA; CLUSTER REGION REARRANGEMENT; MYELODYSPLASTIC SYNDROMES; RAS MUTATIONS; CLASSIFICATION; FEATURES; CMML AB We have reviewed our experience with four of the entities that are included under the generic term chronic myeloid leukaemia (CML), namely the classic Ph(+) CGL, both BCR(+) and BCR(-), aCML and CMML. We have developed a statistical model that confirms that CGL, aCML and CMML can be distinguished from each other with reasonable success employing five quantitative parameters (WBC, percentage immature granulocytes, percentage monocytes, percentage basophils, percentage erythroid precursors in bone marrow) and one qualitative parameter (granulocytic dysplasia). It is hoped that these detailed recommendations will enable investigators to improve their diagnostic accuracy. This should permit more uniform comparisons of molecular biologic and clinical studies. C1 ROYAL MARSDEN HOSP,ACAD DEPT HAEMATOL & CYTOGENET,LONDON SW3 6JJ,ENGLAND. HOP ST LOUIS,CENT LAB HAEMATOL & CYTOL,PARIS,FRANCE. GRP HOSP NECKER ENFANTS MALADES,CENT LAB HAEMATOL,PARIS,FRANCE. ROYAL POSTGRAD MED SCH,MRC,LEUKAEMIA UNIT,LONDON,ENGLAND. NIH,CTR CLIN,SERV HEMATOL,BETHESDA,MD 20892. HENRI MONDOR HOSP,CENT LAB HAEMATOL & IMMUNOL,CRETEIL,FRANCE. UNIV ROCHESTER,MED CTR,DEPT BIOSTAT,ROCHESTER,NY 14642. RP BENNETT, JM (reprint author), UNIV ROCHESTER,CTR CANC,BOX 704,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. NR 27 TC 289 Z9 299 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 1994 VL 87 IS 4 BP 746 EP 754 DI 10.1111/j.1365-2141.1994.tb06734.x PG 9 WC Hematology SC Hematology GA PB740 UT WOS:A1994PB74000013 PM 7986717 ER PT J AU FRICKHOFEN, N CHEN, ZJ YOUNG, NS COHEN, BJ HEIMPEL, H ABKOWITZ, JL AF FRICKHOFEN, N CHEN, ZJ YOUNG, NS COHEN, BJ HEIMPEL, H ABKOWITZ, JL TI PARVOVIRUS B19 AS A CAUSE OF ACQUIRED CHRONIC PURE RED-CELL APLASIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE PARVOVIRUS; ANEMIA; PURE RED CELL APLASIA; INFECTION; DNA; PCR ID POLYMERASE CHAIN-REACTION; IMMUNOGLOBULIN THERAPY; LYMPHOCYTIC-LEUKEMIA; HUMAN-SERUM; INFECTION; VIRUS; ANTIBODIES; ANEMIA; DNA; CYCLOSPORINE AB Parvovirus B19 infection causes chronic anaemia in immunodeficient individuals by selective suppression of erythropoiesis. The bone marrow morphology is characteristic of pure red cell aplasia (PRCA). To determine the frequency of B19-induced PRCA we retrospectively analysed a series of 57 PRCA patients. B19 DNA was present in serum of eight patients (14%) and could be extracted from bone marrow aspirate slides from five of these patients. Recent exposure to the virus was confirmed by the presence of anti-B19 IgM in sera from four and by the finding of giant pronormoblasts in marrow aspirates from five of the B19 DNA-positive patients. The sensitivities of anti-B19 IgM and of giant pronormoblasts were only 50% and 63%, respectively; specificities were 90% and 92%. Unexpectedly, PRCA in two B19 DNA-positive patients remitted after antilymphocyte globulin or cyclosporin A therapy, suggesting that the clinical course of B19-induced PRCA may be indistinguishable from other forms of PRCA. As therapy with immunoglobulin is uniformly effective for treatment of B19-associated anaemia, our data suggest that all patients with acquired PRCA should be evaluated for evidence of B19 infection. B19 DNA analysis is the most reliable method to demonstrate infection. C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. CENT PUBL HLTH LAB,LONDON,ENGLAND. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. RP FRICKHOFEN, N (reprint author), UNIV ULM,DEPT MED 3,D-89081 ULM,GERMANY. FU NHLBI NIH HHS [R0I HL 31826] NR 29 TC 48 Z9 51 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 1994 VL 87 IS 4 BP 818 EP 824 DI 10.1111/j.1365-2141.1994.tb06743.x PG 7 WC Hematology SC Hematology GA PB740 UT WOS:A1994PB74000022 PM 7986722 ER PT J AU BRODSKY, RA HASEGAWA, S FIBACH, E DUNBAR, CE YOUNG, NS RODGERS, GP AF BRODSKY, RA HASEGAWA, S FIBACH, E DUNBAR, CE YOUNG, NS RODGERS, GP TI ACQUIRED SIDEROBLASTIC ANEMIA FOLLOWING PROGESTERONE THERAPY SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Note DE SIDEROBLASTIC ANEMIA; PROGESTERONE; HEME; ERYTHROPOIESIS; PORPHYRIN ID PROLIFERATION; UTEROFERRIN; ANEMIA AB We report a case of acquired sideroblastic anaemia precipitated by progesterone. On two separate occasions, over 15 years apart, the patient developed sideroblastic anaemia with iron overload shortly after the administration of progesterone. No other cause for sideroblastic anaemia was found, and treatment with folic acid, pyridoxine or androgens corrected the anaemia. In both instances removal of the progestational agent led to prompt disappearance of the anaemia as well as the ringed sideroblasts. Using a two-phase liquid culture procedure in which human peripheral blood-derived progenitor cells undergo erythroid proliferation and differentiation, we demonstrated enhanced sensitivity of the patient's erythroid progenitors to progesterone. We conclude that progesterone should be added to the list of medications known to be associated with acquired sideroblastic anaemia. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIDDKD,BIOL CHEM LAB,BETHESDA,MD. NR 10 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 1994 VL 87 IS 4 BP 859 EP 862 DI 10.1111/j.1365-2141.1994.tb06753.x PG 4 WC Hematology SC Hematology GA PB740 UT WOS:A1994PB74000032 PM 7986730 ER PT J AU BO, XN FISCHER, B MAILLARD, M JACOBSON, KA BURNSTOCK, G AF BO, XN FISCHER, B MAILLARD, M JACOBSON, KA BURNSTOCK, G TI COMPARATIVE-STUDIES ON THE AFFINITIES OF ATP DERIVATIVES FOR P-2X-PURINOCEPTORS IN RAT URINARY-BLADDER SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE P-2X-PURINOCEPTORS; URINARY BLADDER; [H-3] ALPHA,BETA-METHYLENE ATP; ATP DERIVATIVES; SURAMIN; REACTIVE BLUE 2; PPADS; RADIOLIGAND BINDING ASSAY ID PIG TAENIA-COLI; H-3 ALPHA,BETA-METHYLENE ATP; VAS-DEFERENS; BINDING-SITES; DIADENOSINE TETRAPHOSPHATE; SYNAPTIC TRANSMISSION; ADENINE DINUCLEOTIDES; MAMMALIAN NEURONS; SMOOTH-MUSCLE; NUCLEOTIDES AB 1 Radioligand binding assays have been used to determine the affinities of a series of ATP derivatives with modifications of the polyphosphate chain, adenine and ribose moieties of the ATP molecule for [H-3]-alpha,beta-methylene ATP ([H-3]-alpha,beta-MeATP) binding sites in rat urinary bladder. 2 The replacement of the bridging oxygen in the triphosphate chain of ATP (pIC(50) = 5.58) with a methylene or imido group markedly increased the affinity (691 fold in IC50 values for beta,gamma-imidoATP, 15 fold for beta,gamma-methylene ATP), and the replacement of an ionized oxygen on the gamma-phosphate with a sulphur (ATP gamma S) also led to increased affinity (5623 fold in IC50 values). 3 Modifications at N-6, N-1, and C-8 positions on the purine base usually reduced the affinity of ATP (a decrease of 2.8 fold in IC50 values for N-6-methylATP and 8.9 fold for 8-bromo ATP), while the attachment of an alkylthio group to the C-2 position greatly increased the affinity for P-2X-purinoceptors (from 3.5 to 98 fold increase in IC50 values). 4 Replacement of the 3'-hydroxyl group on the ribose with substituted amino or acylamino groups produced more potent P-2X-purinoceptor agonists (an increase of 447 fold in IC50 values for 3'-deoxy-3'-benzylamino ATP and 28 fold for 3'-deoxy-3'-(4-hydroxyphenylpropionyl)amino ATP. 5 Diadenosine polyphosphates (Ap[n]A) were also shown to displace the [H-3]-alpha,beta-MeATP binding. The rank order of potency was Ap6A > Ap5A > Ap4A >> Ap3A >> Ap2A. 6 Suramin, PPADS, and reactive blue 2 could competitively displace the binding of [H-3]-alpha,beta-MeATP to P-2X-purinoceptors, with pIC(50) values of 6.26, 5.35, and 6.22, respectively. C1 UNIV LONDON UNIV COLL,DEPT ANAT & DEV BIOL,LONDON WC1E 6BT,ENGLAND. UNIV LONDON UNIV COLL,CTR NEUROSCI,LONDON WC1E 6BT,ENGLAND. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Bo, Xuenong/E-9845-2012; Jacobson, Kenneth/A-1530-2009 OI Bo, Xuenong/0000-0002-9202-3562; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 52 TC 54 Z9 55 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 1994 VL 112 IS 4 BP 1151 EP 1159 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ829 UT WOS:A1994NZ82900025 PM 7952876 ER PT J AU MEHNERT, R AF MEHNERT, R TI COMPUTER ACCESS TO CLINICAL-PRACTICE GUIDELINES SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Letter RP MEHNERT, R (reprint author), NIH,NATL LIB MED,OFF PUBL INFORMAT,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD AUG 1 PY 1994 VL 151 IS 3 BP 273 EP 273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NZ083 UT WOS:A1994NZ08300015 PM 8039078 ER PT J AU YAMAMOTO, N TOKUNAGA, M UEMURA, Y TANAKA, S SHIRAHAMA, H NAKAMURA, T LAND, CE SATO, E AF YAMAMOTO, N TOKUNAGA, M UEMURA, Y TANAKA, S SHIRAHAMA, H NAKAMURA, T LAND, CE SATO, E TI EPSTEIN-BARR-VIRUS AND GASTRIC REMNANT CANCER SO CANCER LA English DT Article DE EPSTEIN-BARR VIRUS; GASTRIC CANCER; GASTRIC REMNANT CANCER; EBER-1 IN SITU HYBRIDIZATION ID BENIGN GASTRODUODENAL DISEASES; PARTIAL GASTRECTOMY; STUMP CANCER; CARCINOMA; STOMACH; SURGERY; JAPAN AB Background. Carcinoma arising in the gastric remnant many years after partial gastrectomy for benign disease, referred to as gastric remnant cancer (GRC) is well known, and many causal explanations have been proposed. Elsewhere, Epstein-Barr virus (EBV) involvement has been demonstrated in a small but significant fraction of gastric cancers, and evidence has been presented suggesting that, in positive cases, EBV may have played a causal role. The present report is concerned with EBV involvement in GRC in particular. Methods. Paraffin sections from 48 cases of GRC were studied by EBER-1 in situ hybridization. Results. Thirteen cases (27.1%) showed uniform hybridized signals restricted to the carcinoma cells in contrast to no hybridization in the normal mucosa, intestinal metaplasia, or hyperplastic epithelium. The prevalence of EBV involvement in GRC was significantly higher (P < 0.0001) than in gastric carcinomas from 1825 nonremnant cases; the difference remained highly significant even when the comparison was restricted to nonremnant cancers arising in the cardia and middle stomach, for which EBV-positive rates were highest. Conclusion. The EBV may play an important role in the carcinogenesis of GRC. C1 KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA 892,JAPAN. KAGOSHIMA UNIV,SCH MED,DEPT PATHOL 2,KAGOSHIMA 890,JAPAN. KAGOSHIMA CITY MED ASSOC HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. KAGOSHIMA PREVENT MED INST,DEPT PATHOL,IJYUIN,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 19 TC 53 Z9 56 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1994 VL 74 IS 3 BP 805 EP 809 DI 10.1002/1097-0142(19940801)74:3<805::AID-CNCR2820740304>3.0.CO;2-L PG 5 WC Oncology SC Oncology GA NZ352 UT WOS:A1994NZ35200003 PM 8039108 ER PT J AU SONDIK, EJ AF SONDIK, EJ TI BREAST-CANCER TRENDS - INCIDENCE, MORTALITY, AND SURVIVAL SO CANCER LA English DT Article; Proceedings Paper CT Conference on Breast Cancer Research: Current Issues - Future Directions CY APR 25-28, 1993 CL ATLANTA, GA AB This paper describes trends in the primary measures of breast cancer. Data on incidence and mortality are drawn from the Surveillance, Epidemiology, and End Results Program, and those on mortality are from the National Center for Health Statistics. There has been a steady increase in the rate of breast cancer cases since 1950, with a sharp rise in the 1980s because of the increased use of mammography. Conversely, mortality since 1973 has declined by 11% for women younger than 50 (the decrease is primarily in the 70s) and increased by 6% for women aged 50 and older. There are different racial experiences in breast cancer incidence, with African-American women aged 40 and older having a lower incidence rate, and those younger than 40 having a higher one. For all ages, there is a greater likelihood of mortality (lower survival) for each case. This paper explores these trends and their implications for the future impact of this disease. RP SONDIK, EJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,BLDG 31,ROOM 10-A-49,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 3 TC 55 Z9 56 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1994 VL 74 IS 3 SU S BP 995 EP 999 DI 10.1002/1097-0142(19940801)74:3+<995::AID-CNCR2820741504>3.0.CO;2-M PG 5 WC Oncology SC Oncology GA NZ821 UT WOS:A1994NZ82100002 PM 8039156 ER PT J AU SNYDERWINE, EG AF SNYDERWINE, EG TI SOME PERSPECTIVES ON THE NUTRITIONAL ASPECTS OF BREAST-CANCER RESEARCH - FOOD-DERIVED HETEROCYCLIC AMINES AS ETIOLOGIC AGENTS IN HUMAN MAMMARY-CANCER SO CANCER LA English DT Article; Proceedings Paper CT Conference on Breast Cancer Research: Current Issues - Future Directions CY APR 25-28, 1993 CL ATLANTA, GA DE MUTAGENS; COOKED MEATS; MAMMARY GLAND CANCER; HETEROCYCLIC AMINES; METABOLIC ACTIVATION; DIETARY CARCINOGENS ID FRIED GROUND-BEEF; PAN-BROILED PORK; COOKED FOOD; AROMATIC-AMINES; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE IQ; METABOLIC-ACTIVATION; PYROLYSIS PRODUCTS; HUMAN-URINE; MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; TRYPTOPHAN-PYROLYSATE AB Epidemiologic and experimental evidence indicates that dietary factors influence the incidence of mammary gland cancer. The dietary causes of this cancer, however, remain largely unknown. This paper reviews the experimental studies implicating the food-derived heterocyclic amines (HAs) in human breast cancer. Heterocyclic amines are formed at the parts-per-billion levels in meats, such as beef, chicken, pork, and fish, cooked by ordinary methods. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is among the most prevalent of the HAs in fried and barbecued beef, a staple of the American diet. Chronic administration of PhIP in the diet has been shown to cause mammary gland cancer in rats. Two other food-derived HAs, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, also have been shown to be mammary carcinogens in rodent models. In rats, heterocyclic amines produce DNA adducts in the mammary gland after metabolic activation. Studies examining human urine for HAs and metabolites confirm that humans who consume cooked meats are exposed to HAs. Studies also reveal that humans can activate HAs metabolically. Therefore, the experimental evidence suggests that the food-derived HAs may be etiologic agents in human breast cancer. Humans, however, are exposed to a complex mixture of carcinogenic and anticarcinogenic agents through their diets. Experimental studies examining the interaction between HAs and other dietary factors with respect to mammary carcinogenesis are warranted. RP SNYDERWINE, EG (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 88 TC 93 Z9 95 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1994 VL 74 IS 3 SU S BP 1070 EP 1077 DI 10.1002/1097-0142(19940801)74:3+<1070::AID-CNCR2820741515>3.0.CO;2-7 PG 8 WC Oncology SC Oncology GA NZ821 UT WOS:A1994NZ82100013 PM 8039141 ER PT J AU BALLARDBARBASH, R AF BALLARDBARBASH, R TI ANTHROPOMETRY AND BREAST-CANCER - BODY-SIZE - A MOVING TARGET SO CANCER LA English DT Article; Proceedings Paper CT Conference on Breast Cancer Research: Current Issues - Future Directions CY APR 25-28, 1993 CL ATLANTA, GA DE BREAST CANCER; DEVELOPMENT; PROGNOSIS; HEIGHT; WEIGHT; BODY-FAT DISTRIBUTION; WEIGHT GAIN; OVARIAN HORMONES; INSULIN; METABOLISM ID ESTROGEN REPLACEMENT THERAPY; HORMONE BINDING GLOBULIN; FAT DISTRIBUTION; RISK-FACTORS; POSTMENOPAUSAL WOMEN; SEX-HORMONES; WEIGHT-GAIN; MASS INDEX; REPRODUCTIVE FACTORS; PREMENOPAUSAL WOMEN AB Body size is one of the few breast cancer risk factors that can be modified throughout life and therefore should be considered in research on breast cancer prevention. The contrasting effects of body size on premenopausal breast cancer compared with postmenopausal breast cancer and the lack of a strong association between body mass and postmenopausal breast cancer in some cohort studies has led to a view that obesity has little influence on breast cancer risk. These conclusions are based on analyses that consider relative weight at one point in time as an adequate measure of lifelong weight patterns and their metabolic consequences. Recent research suggests that, compared to body mass indices, adult weight gain and increased central body fat may be more specific markers of the metabolic consequences of obesity and therefore may predict health outcomes more consistently. Adult weight gain and increases in central body fat, which commonly occur during menopause, have been associated consistently with an increased risk of postmenopausal breast cancer. The timing of weight gain also appears to influence breast cancer risk; increased relative weight and weight gain after menopause have been associated with the largest increases in relative risks. Overall levels of adiposity, increased central fat deposition, and weight gain are associated with alterations in ovarian hormone and glucose metabolism and in growth factors that may promote breast cancer cell growth. Data on lifelong weight changes and the location of fat depots may more precisely identify women with high risk patterns of sex steroid and glucose metabolism. Similarly, research is needed to determine if weight gain during periods of hormonal change, such as menarche, pregnancy, and menopause, have different biologic effects, perhaps because of differences in the location of fat deposition during these periods. Research also is needed on whether there are critical times relative to breast cancer promotion when excessive weight gain should be avoided. Data are lacking on the influence of weight loss or avoidance of weight gain on breast cancer risk or prognosis. Cancer 1994; 74:1090-100. C1 NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,BETHESDA,MD 20892. NR 112 TC 126 Z9 127 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1994 VL 74 IS 3 SU S BP 1090 EP 1100 DI 10.1002/1097-0142(19940801)74:3+<1090::AID-CNCR2820741518>3.0.CO;2-X PG 11 WC Oncology SC Oncology GA NZ821 UT WOS:A1994NZ82100016 PM 8039144 ER PT J AU SCHATZKIN, A LONGNECKER, MP AF SCHATZKIN, A LONGNECKER, MP TI ALCOHOL AND BREAST-CANCER - WHERE ARE WE NOW AND WHERE DO WE GO FROM HERE SO CANCER LA English DT Article; Proceedings Paper CT Conference on Breast Cancer Research: Current Issues - Future Directions CY APR 25-28, 1993 CL ATLANTA, GA DE ETHANOL; BREAST NEOPLASMS; EPIDEMIOLOGY; METAANALYSIS; ESTROGENS ID SELF-ADMINISTERED QUESTIONNAIRE; PITUITARY-GONADAL-HORMONES; BEVERAGE CONSUMPTION; POSTMENOPAUSAL WOMEN; CIGARETTE-SMOKING; RISK-FACTORS; MAMMARY TUMORIGENESIS; PREMENOPAUSAL WOMEN; LUTEINIZING-HORMONE; SEX-HORMONES AB The alcohol-breast cancer hypothesis is important because (1) breast cancer is a major source of morbidity and mortality, (2) alcohol consumption is common, and (3) drinking is modifiable. Reports from more than 50 epidemiologic investigations of this hypothesis have now appeared. A recent metaanalysis of these studies indicates both a modest positive association between alcohol and breast cancer (an approximate 25% increase in risk with daily intake of the equivalent of two drinks) and a dose-response relation. Data suggest that risk increases with consumption of alcohol in general, regardless of beverage type. Several factors, including age, weight, and estrogen usage, have been shown to modify this relation in some studies. The authors discuss a series of methodologic issues in the study of alcohol and breast cancer. These include error in alcohol assessment, difficulties in evaluating small relative risks, and the potential for confounding. Several biologic mechanisms could account for an alcohol-breast cancer relation, with increasing attention being paid to a possible mediating effect of reproductive steroid hormones. Animal studies are a relatively recent development in this area; results have been mixed. Incorporation of more refined temporal, quantitative, and qualitative indicators of alcohol exposure in future epidemiologic studies would be valuable, as would further exploration of the endocrine and other metabolic effects of moderate alcohol consumption. The alcohol-breast cancer hypothesis remains intriguing, but causality has not been established. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. RP SCHATZKIN, A (reprint author), NCI,DIV CANC PREVENT & CONTROL,9000 ROCKVILLE PIKE,EPN 211,BETHESDA,MD 20892, USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 112 TC 62 Z9 62 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1994 VL 74 IS 3 SU S BP 1101 EP 1110 DI 10.1002/1097-0142(19940801)74:3+<1101::AID-CNCR2820741519>3.0.CO;2-X PG 10 WC Oncology SC Oncology GA NZ821 UT WOS:A1994NZ82100017 PM 8039145 ER PT J AU ABRAMS, JS MOORE, TD FRIEDMAN, M AF ABRAMS, JS MOORE, TD FRIEDMAN, M TI NEW CHEMOTHERAPEUTIC-AGENTS FOR BREAST-CANCER SO CANCER LA English DT Article; Proceedings Paper CT Conference on Breast Cancer Research: Current Issues - Future Directions CY APR 25-28, 1993 CL ATLANTA, GA DE CHEMOTHERAPY; TAXOL; TAXOTERE; VINORELBINE; EDATREXATE ID PHASE-I TRIAL; PRECLINICAL ANTITUMOR-ACTIVITY; SQUAMOUS-CELL CARCINOMA; METHYL-N-NITROSOUREA; TRANS-RETINOIC ACID; FOLATE ANALOGS; 10-DEAZA-AMINOPTERIN SERIES; TUMOR-CELLS; 13-CIS-RETINOIC ACID; SCHEDULE DEPENDENCE AB The drug discovery programs of the National Cancer Institute and the pharmaceutical industry recently have provided oncologists with a wide array of new chemotherapeutic agents that have considerable potential for breast cancer treatment. Foremost among these new agents are the taxanes, of which paclitaxel and docetaxel, the only members of this class currently in clinical use, have been associated with impressive response rates in patients with metastatic disease. Importantly, they display some evidence clinically of not being cross-resistant with the anthracyclines. Efforts now are being directed toward optimizing dose and schedule in the metastatic setting while integrating these agents into standard adjuvant regimens. Other agents that have undergone Phase II testing in breast cancer include vinorelbine, edatrexate, and losoxantrone. It remains to be determined, however, whether these drugs possess substantial advantages over other members of their class. Newer compounds, such as pyrazoloacridine, ICI D1694, topoisomerase-I inhibitors, temozolomide, penclomidine, fumagillin (TNP-470), and differentiators like the retinoids, hold substantial promise because of their unique mechanisms of action; however, Phase II testing of these agents is just beginning. Although alternative approaches to treatment, such as gene therapies, monoclonal antibodies, and growth factor inhibitors, are likely to have a positive impact, it is probable that progress will best be made by combining these strategies with chemotherapy. Therefore, continuation of the search for more effective chemotherapeutic agents should remain a high priority. C1 NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. NCI,CLIN INVEST BRANCH,BETHESDA,MD 20892. RP ABRAMS, JS (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,ROOM 741,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 127 TC 28 Z9 28 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1994 VL 74 IS 3 SU S BP 1164 EP 1176 DI 10.1002/1097-0142(19940801)74:3+<1164::AID-CNCR2820741528>3.0.CO;2-K PG 13 WC Oncology SC Oncology GA NZ821 UT WOS:A1994NZ82100026 PM 7913662 ER PT J AU SHAMAMIAN, P MANCINI, M KAWAKAMI, Y RESTIFO, NP ROSENBERG, SA TOPALIAN, SL AF SHAMAMIAN, P MANCINI, M KAWAKAMI, Y RESTIFO, NP ROSENBERG, SA TOPALIAN, SL TI RECOGNITION OF NEUROECTODERMAL TUMORS BY MELANOMA-SPECIFIC CYTOTOXIC T-LYMPHOCYTES - EVIDENCE FOR ANTIGEN SHARING BY TUMORS DERIVED FROM THE NEURAL CREST SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE MELANOMA; NEURAL CREST; EWINGS SARCOMA; TUMOR-INFILTRATING LYMPHOCYTE ID INFILTRATING LYMPHOCYTES; EWINGS-SARCOMA; CELL CLONES; IFN-GAMMA; RESTRICTION; EXPRESSION; GENE; HLA; IDENTIFICATION; IMMUNOTHERAPY AB Melanomas from different patients have been shown to express shared tumor antigens, which can be recognized in the context of the appropriate MHC class I molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens are expressed on other tumors of neuroectodermal origin, four melanoma-specific cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes (TIL) were tested for lysis of a panel of 23 HLA-A2(+) neuroectodermal tumor cell lines of various histologies, including retinoblastoma (1), neuroblastoma (8), neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5). Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23 neuroectodermal tumor lines, and could be enhanced by treatment with interferon gamma (IFN gamma). Following TFN gamma treatment, three Ewing's sarcoma lines were lysed by at least one melanoma TIL culture, and levels of lysis were comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal antibodies directed against MHC class I molecules and against CD3, indicating specific immune recognition of tumor-associated antigens. None of the other neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non-MHC-restricted lymphokine-activated killer cells. This demonstration of immunological cross-reactivity between Ewing's sarcomas, two tumors of distinct histological types with a common embryonic origin, has implications for the developmental nature of these CTL-defined tumor antigens. It also raises the possibility that specific antitumor immunotherapies, such as vaccines, may be reactive against more than one form of cancer. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 31 TC 16 Z9 16 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD AUG PY 1994 VL 39 IS 2 BP 73 EP 83 DI 10.1007/BF01525312 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA NX358 UT WOS:A1994NX35800001 PM 7519127 ER PT J AU SALGALLER, ML WEBER, JS KOENIG, S YANNELLI, JR ROSENBERG, SA AF SALGALLER, ML WEBER, JS KOENIG, S YANNELLI, JR ROSENBERG, SA TI GENERATION OF SPECIFIC ANTIMELANOMA REACTIVITY BY STIMULATION OF HUMAN TUMOR-INFILTRATING LYMPHOCYTES WITH MAGE-1 SYNTHETIC PEPTIDE SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE MELANOMA; MAGE-1; TUMOR-INFILTRATING LYMPHOCYTES; IMMUNOTHERAPY; PEPTIDE ID T-CELL CLONES; HUMAN GENE MAGE-1; CLASS-I ANTIGENS; ADOPTIVE IMMUNOTHERAPY; PROLIFERATE INVIVO; REJECTION ANTIGEN; INTERFERON-GAMMA; NECROSIS-FACTOR; B-CELLS; VIRUS AB The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a patient with melanoma. We have produced a MAGE-1-specific CTL line derived from the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1-restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277.A TIL line grew in long-term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen-specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-(1+) cell lines. Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY was superior to that of cells pulsed with the immunodominant nonapeptide. Single amino-acid or even side-chain substitutions in the immunodominant nonamer abrogated cytolysis. 1277.A TIL specifically secreted tumor necrosis factor a after co-incubation with HLA-A1-expressing MAGE-(1+) cell lines or fresh tumor. These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown from TIL in the presence of synthetic epitope peptides and expanded for adoptive immunotherapy in melanoma patients. C1 MEDIMMUNE INC,GAITHERSBURG,MD 20877. RP SALGALLER, ML (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B08,BETHESDA,MD 20892, USA. NR 56 TC 70 Z9 71 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD AUG PY 1994 VL 39 IS 2 BP 105 EP 116 DI 10.1007/s002620050101 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA NX358 UT WOS:A1994NX35800005 PM 7519125 ER PT J AU HERZOG, CR WISEMAN, RW YOU, M AF HERZOG, CR WISEMAN, RW YOU, M TI DELETION MAPPING OF A PUTATIVE TUMOR-SUPPRESSOR GENE ON CHROMOSOME-4 IN MOUSE LUNG-TUMORS SO CANCER RESEARCH LA English DT Note ID HOMOZYGOUS DELETIONS; CRITICAL REGION; INTERFERON; MELANOMA; HYBRIDS; ALPHA AB Genetic and molecular studies have implicated the region of the alpha-interferon gene cluster on mouse chromosome 4 as the location of a putative tumor suppressor gene. A region of homology on human chromosome 9p21-22 that is frequently deleted in multiple human cancers has recently been found to contain a candidate tumor suppressor gene called multiple tumor suppressor-1 (MTS1), which was previously shown to encode an inhibitor of cyclin-dependent kinase 4. We performed loss of heterozygosity and deletion analyses to map the most commonly deleted region on chromosome 4 in F-1 hybrid mouse lung tumors. Ten simple sequence length polymorphism markers were analyzed with focus on the alpha-interferon region. Allelic losses were detected in 29 of 61 (48%) of the lung adenocarcinomas but in only 1 of 38 (3%) of the lung adenomas examined. In most cases, the losses appeared to occur by nondisjunction. However, in three carcinomas, we detected homozygous deletions that overlapped at simple sequence length polymorphism marker D4MIT77. These data suggest a critical region of about 2 cM immediately distal to the alpha-interferon locus as the likely domain of a novel tumor suppressor gene on mouse chromosome 4, the loss of which appears to be involved in the progression of mouse lung tumorigenesis. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. NIEHS,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA58554] NR 21 TC 62 Z9 62 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 AUG 1 PY 1994 VL 54 IS 15 BP 4007 EP 4010 PG 4 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600014 PM 8033131 ER PT J AU STUBBS, M RODRIGUES, L HOWE, FA WANG, J JEONG, KS VEECH, RL GRIFFITHS, JR AF STUBBS, M RODRIGUES, L HOWE, FA WANG, J JEONG, KS VEECH, RL GRIFFITHS, JR TI METABOLIC CONSEQUENCES OF A REVERSED PH GRADIENT IN RAT-TUMORS SO CANCER RESEARCH LA English DT Article ID P-31-NMR SPECTROSCOPY; INTRACELLULAR PH; CANCER-CELLS; INVIVO; MAGNESIUM; LACTATE; LIVER; MRS; NMR AB We have previously demonstrated (M. Stubbs, Z. M. Bhujwalla, G. M. Tozer, L. M. Rodrigues, R. J. Maxwell, R. Morgan, P. A. Howe, and J. R Griffiths, NMR Biomed., 5: 351, 1992) that the intracellular pH (pH(i)) of several rat tumors is higher (> pH 7.0) than that of the tumor extracellular fluid (pH(e)), in contrast to normal tissues (e.g., liver) in which pH(i) is lower than pH(e)). In this paper we confirm a pH(e) of 6.8 +/- 0.07 (SEM) in Morris hepatoma 9618a by an independent method and report the tissue content of other ions by both P-31 magnetic resonance spectroscopy and by conventional analysis in hepatomas and livers in rats. Compared with liver, tissue Na+ was 2-fold higher and tissue K+ was lower. Tissue Ca2+ was 8-fold higher (7.4 +/- 4.3 mu mol/g wet weight) and tissue P-i was 2-fold higher (8.5 +/- 1.3 mu mol/g wet weight) suggesting the presence of insoluble calcium phosphate. Cl- was unchanged (similar to 40 mu mol/g wet weight), whereas HCO3- was lower in the hepatoma (12.4 +/- 0.83 compared to 15.5 +/- 0.76 mu mol/g wet weight). Total tissue Mg2+ was similar in both tissues, but free [Mg2+] (calculated by two different methods) was similar to 5-fold lower in the hepatoma. The ATP values were 3.5-fold and [NAD]/[NADH] 9-fold lower in the hepatoma. The results are compatible with the hypothesis that the chronic partial hypoxia of tumor tissue involves changes in the linked equilibria of many ions and metabolites and may help explain such pathologies as calcification. C1 ST GEORGE HOSP,SCH MED,DIV BIOCHEM,CANC RES CAMPAIGN,BIOMED MAGNET RESONANCE RES GRP,LONDON SW17 0RE,ENGLAND. NIAAA,METAB LAB,ROCKVILLE,MD 20892. RI Howe, Franklyn/C-3307-2008; Griffiths, John/F-2853-2010 NR 48 TC 106 Z9 107 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1994 VL 54 IS 15 BP 4011 EP 4016 PG 6 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600015 PM 8033132 ER PT J AU LEWIS, KC ZECH, LA PHANG, JM AF LEWIS, KC ZECH, LA PHANG, JM TI EFFECTS OF N-(4-HYDROXYPHENYL)RETINAMIDE SUPPLEMENTATION ON VITAMIN-A METABOLISM SO CANCER RESEARCH LA English DT Article ID RETINOL-BINDING PROTEIN; BREAST-CANCER PATIENTS; PLASMA RETINOL; PROSTATE-CANCER; A STATUS; FENRETINIDE; RATS; LIVER; CAROTENOIDS; PREVENTION AB The efficacy of the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been demonstrated in the inhibition of cancers in a variety of tissues. Moreover, toxicity effects following administration of 4-HPR have been found to be reduced or absent when compared to other retinoids. Pharmacokinetic studies in both animals and humans have focused on the metabolism of 4-HPR and its metabolites, and relatively little information has been published detailing the effects of long-term administration of 4-HPR upon normal endogenous vitamin A metabolism. Thus, the present study was carried out to examine the effects of long-term administration of 4-HPR upon plasma and tissue vitamin A kinetics. Male Sprague-Dawley rats were fed either a control diet sufficient in vitamin A [CON group; 1.0 retinol (ROH) equivalents/g diet] or a CON diet supplemented with 4-HPR (CON+4HPR group; 1173 mu g 4-HPR/g diet). Following i.v. injection of a physiologically radiolabeled dose of ROH, ROH tracer and tracee kinetics were monitored in plasma and tissues over a 41-day period. Kinetic parameters were determined using the SAAM/CONSAM computer modeling programs to carry out graphical analysis of the tracer concentration curves. Mean plasma ROH levels measured for the CON+4HPR group were reduced to one-third of those of the CON group. Most of the kinetic parameters calculated were found to be significantly altered by the inclusion of 4-HPR in the diet. The fraction of the plasma ROH being catabolized per day (fractional catabolic rate) was nearly twice as high in the CON+4HPR treated group (3.61 +/- 0.49 day(-1); mean +/- SD) as compared to the CON group (2.00 +/- 0.68 day(-1)). The amount of time that vitamin A molecules spent in the body before being lost irreversibly from the system (system residence time) was decreased by half in the CON+4HPR group (19.20 +/- 7.13 days) versus the CON group (38.63 +/- 9.62 days). Despite the increased catabolic rates and decreased system residence times measured for the CON+4HPR group, the estimated vitamin A use in these animals (11.01 +/- 3.10 mu g/day) was 33% less than that used by the CON group (16.31 +/- 2.47 mu g/day). Studies investigating the mechanisms by which 4-HPR alters vitamin A kinetics are presently under way in our laboratory. Nevertheless, these results suggest that long-term administration of 4-HPR markedly perturbs normal vitamin A metabolism in rats. Whether 4-HPR similarly alters human vitamin A metabolism with untoward clinical consequences deserves careful evaluation. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP LEWIS, KC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,NUTR & MOLEC REGULAT LAB,POB B,FREDERICK,MD 21702, USA. NR 31 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1994 VL 54 IS 15 BP 4112 EP 4117 PG 6 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600029 PM 8033144 ER PT J AU MINEV, BR MCFARLAND, BJ SPIESS, PJ ROSENBERG, SA RESTIFO, NP AF MINEV, BR MCFARLAND, BJ SPIESS, PJ ROSENBERG, SA RESTIFO, NP TI INSERTION SIGNAL SEQUENCE FUSED TO MINIMAL PEPTIDES ELICITS SPECIFIC CD8+ T-CELL RESPONSES AND PROLONGS SURVIVAL OF THYMOMA-BEARING MICE SO CANCER RESEARCH LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC LYMPHOCYTES-T; FREE SYNTHETIC PEPTIDE; CLASS-I MOLECULES; ENDOPLASMIC-RETICULUM; SOLUBLE-PROTEIN; DENDRITIC CELLS; INVIVO; ANTIGEN; INDUCTION AB CD8(+) T-lymphocytes (T-CD8+) recognize minimal peptides of 8-10 residues which are the products of intracellularly processed proteins and are presented at the cell surface by major histocompatibility complex class I molecules. An important step in this process is the translocation of processed proteins from the cytosol across the endoplasmic reticulum membrane, mediated by transporter associated with antigen-processing proteins or alternatively by endoplasmic reticulum-insertion signal sequences located at the NH2-terminus of the precursor molecules. We report here that the addition of an endoplasmic reticulum-insertion signal sequence at the NH2-terminus of T-CD8+ epitopes from chicken ovalbumin (amino acids 257-264) or a naturally occurring tumor antigen expressed by the murine mastocytoma P815 (P1A amino acids 35-43) significantly enhanced the priming of specific T-CD8+ in vivo. The signal sequence did not enhance peptide immunogenicity by merely increasing the hydrophobicity of the peptide, since ovalbumin amino acids 257-264 peptide with the signal sequence at its COOH-terminus did not demonstrate enhanced efficacy. The signal sequence did not act as a helper epitope, since T-CD8+ responses were not diminished in class II-deficient transgenic mice or in mice depleted of CD4(+) T-cells in vivo. Importantly, a single immunization with the fusion peptide significantly prolonged survival of mice challenged with E.G7OVA, a thymoma transfected with the complementary DNA of chicken ovalbumin. C1 NIH,NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,ROOM 2B-54,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 45 TC 74 Z9 74 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1994 VL 54 IS 15 BP 4155 EP 4161 PG 7 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600036 PM 7518351 ER PT J AU PRESTON, GA LANG, JE MARONPOT, RR BARRETT, JC AF PRESTON, GA LANG, JE MARONPOT, RR BARRETT, JC TI REGULATION OF APOPTOSIS BY LOW SERUM IN CELLS OF DIFFERENT STAGES OF NEOPLASTIC PROGRESSION - ENHANCED SUSCEPTIBILITY AFTER LOSS OF A SENESCENCE GENE AND DECREASED SUSCEPTIBILITY AFTER LOSS OF A TUMOR-SUPPRESSOR GENE SO CANCER RESEARCH LA English DT Article ID HAMSTER EMBRYO FIBROBLASTS; WILD-TYPE P53; V-HA-RAS; C-MYC; ANDROGEN ABLATION; TRANSGENIC MICE; DEATH; TRANSFORMATION; EXPRESSION; ONCOGENE AB A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup(+)I) and non-tumor suppressor stage II (sup(-)II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup(+)I and sup(-)II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup(+)I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G(0)/G(1) phase of the cell cycle. The sup(-)II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup(+)I cells, and sup(-)II cells were injected s.c. into nude mice. At 5 or 21 days after injection, the normal SHE cells were readily retrieved from the mice and grew well in culture. In contrast, few sup(+)I cells were retrieved 5 days after injection and no viable cells were retrieved after 21 days. Sup(-)II cells were not retrieved at either the 5-day or 21-day harvest, and histological examinations of the sites of injection showed the presence of macrophages, eosinophils, and neutrophils, indicating an inflammatory response associated with necrotic cell death. These results indicate that normal SHE cells, although nontumorigenic, were quiescent in vitro and in vivo, whereas sup(+)I and sup(-)II cells died in vitro and in vivo. These findings suggest that in vivo conditions are similar to limited serum conditions in culture. Normal cells in low serum undergo growth arrest and do not die. Cells that have lost a senescence gene and are immortal but at an early stage of preneoplastic progression activate apoptosis when placed in low serum. Cells that have lost a tumor suppressor gene and are at a later stage of preneoplastic progression have decreased susceptibility to apoptotic death. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM CARINOGENESIS PROGRAM,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. NR 44 TC 51 Z9 54 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1994 VL 54 IS 15 BP 4214 EP 4223 PG 10 WC Oncology SC Oncology GA NZ246 UT WOS:A1994NZ24600045 PM 8033154 ER PT J AU DAVIS, LM CASPARY, WJ SAKALLAH, SA MARONPOT, R WISEMAN, R BARRETT, JC ELLIOTT, R HOZIER, JC AF DAVIS, LM CASPARY, WJ SAKALLAH, SA MARONPOT, R WISEMAN, R BARRETT, JC ELLIOTT, R HOZIER, JC TI LOSS OF HETEROZYGOSITY IN SPONTANEOUS AND CHEMICALLY-INDUCED TUMORS OF THE B6C3F1 MOUSE SO CARCINOGENESIS LA English DT Article ID HEPATOCELLULAR-CARCINOMA; SUPPRESSOR GENE; COLORECTAL-CANCER; IDENTIFICATION; MUTATIONS; MARKERS; LOCUS; DNA; HEPATOCARCINOGENESIS; CHROMOSOME-5Q21 AB The B6C3F1 mouse is used worldwide to gauge the carcinogenic hazard posed by chemicals to humans. An assessment of the ability of this rodent model to predict human neoplasia requires an evaluation of similarities and differences in the genetics of tumor formation between these two species. We examined 142 spontaneous and chemically-induced liver tumors isolated from the B6C3F1 mouse for losses of heterozygosity (LOH) at 78 polymorphic loci and compared these results to genetic changes known to occur in human hepatocellular carcinoma. Approximately a third of the 142 mouse tumors exhibited LOH, suggesting that tumor suppressor gene inactivation may be involved in the formation of mouse liver tumors. Most of the LOH observed was restricted to seven chromosome sites and most of the tumors that underwent LOH lost alleles from only one of those seven sites. The relatively few losses seen in these mouse tumors distinguished them from clinical stage human tumors in that, in the mouse tumors, interstitial deletions appeared more frequently than losses of whole chromosomes. Only four mouse tumors lost a whole chromosome. LOH occurred at loci of the. mouse genome syntenic to areas of the human genome known to harbor the Wilms', retinoblastoma, APC, MCC and DCC tumor suppressor genes; these genes have never been associated with hepatocellular carcinomas. Losses observed on chromosomes 5 and 8 (syntenic to human chromosomes 4 and 16) suggest tumor suppressor genes that are common to hepatocellular carcinomas from both species, while losses on chromosome 9 suggest involvement of a previously unidentified tumor suppressor gene. C1 NIH,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC. NIH,EXPTL PATHOL LAB,RES TRIANGLE PK,NC. NIH,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC. APPL GENET LABS INC,MELBOURNE,FL. ROSWELL PK CANC INST,DEPT MOLEC & CELL BIOL,BUFFALO,NY. NR 43 TC 49 Z9 49 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1994 VL 15 IS 8 BP 1637 EP 1645 PG 9 WC Oncology SC Oncology GA PC325 UT WOS:A1994PC32500026 PM 8055644 ER PT J AU WEI, SJC CHANG, RL HENNIG, E CUI, XX MERKLER, KA WONG, CQ YAGI, H JERINA, DM CONNEY, AH AF WEI, SJC CHANG, RL HENNIG, E CUI, XX MERKLER, KA WONG, CQ YAGI, H JERINA, DM CONNEY, AH TI MUTAGENIC SELECTIVITY AT THE HPRT LOCUS IN V-79 CELLS - COMPARISON OF MUTATIONS CAUSED BY BAY-REGION BENZO[A]PYRENE 7,8-DIOL-9,10-EPOXIDE ENANTIOMERS WITH HIGH AND LOW CARCINOGENIC ACTIVITY SO CARCINOGENESIS LA English DT Article ID HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; DOSE-DEPENDENT DIFFERENCES; DIPLOID HUMAN FIBROBLASTS; OPTICAL ENANTIOMERS; CODING REGION; DIOL EPOXIDE; 7,8-DIOL 9,10-EPOXIDES; MAMMALIAN-CELLS; EXCISION REPAIR; DNA AB Earlier studies from our laboratories characterized the mutation profile of the optically active (+)-7R,8S-dihydroxy-9S,10R -epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-BPDE-the ultimate carcinogenic metabolite of benzo[a]pyrene] in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene of Chinese hamster V-79 cells. In the present study, we evaluated the mutation profile of (-)-7S,8R-dihydroxy-9R, 10S-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(-)-BPDE-a weakly carcinogenic or inactive enantiomer] and compared its mutation profile with that of (+)-BPDE. In both diol epoxide enantiomers, the benzylic 7-hydroxy group and epoxide oxygen are trans. The mutation frequency for V-79 cells treated with DMSO vehicle or with a low non-cytotoxic dose (0.5 mu M) or a high cytotoxic dose (2.0 mu M) of (-)-BPDE was 1,25 or 185 8-azaguanine-resistant colonies/10(5) survivors, respectively. Independent 8-azaguanine-resistant clones were isolated, and complementary DNAs were prepared by reverse transcription. The coding region of the HPRT gene was amplified by the polymerase chain reaction and sequenced. Altogether, 92 (-)-BPDE-induced mutant clones were examined. At both doses, base substitutions were the most prevalent mutations observed (present in similar to 70% of the mutant clones), followed by exon deletions (present in similar to 22% of the mutant clones) and frame shift mutations (present in similar to 6% of the mutant clones) in the cDNAs analyzed. At the high cytotoxic dose, 5 out of 36 base substitutions occurred at AT base pairs (14%) and 31 at GC base pairs (86%). At the low non-cytotoxic dose, 7 out of 34 base substitutions were at AT base pairs (21%) and 27 were at GC base pairs (79%). Although there was a trend towards an increase in the proportion of mutations at AT base pairs when the dose of (-)-BPDE was decreased, this trend was not statistically significant. The data also indicated no dose-dependent differences in the kinds of base substitutions or exon deletions in cDNAs induced by (-)-BPDE. Ninety-one per cent of the (-)-BPDE-induced mutations that occurred at guanine were on the non-transcribed strand of DNA and 9% were on the transcribed strand. In contrast to these results, 50% of the (-)-BPDE-induced mutations that occurred at adenine were on the transcribed strand and 50% on the non-transcribed strand. A comparison of the mutation profiles of (-)- and (+)-BPDE revealed that (i) (+)-BPDE is more mutagenic than (-)-BPDE, (ii) (+)-BPDE caused a significantly higher proportion of mutations at AT base pairs as the dose decreased, but this was not observed for (-)-BPDE, (iii) (+)-BPDE showed high selectivity for GC --> TA transversions, but considerably less selectivity was observed for (-)-BPDE, and (iv) (-)-BPDE had different hot spots for base substitutions than did (+)-BPDE. C1 NIDDKD,BIOORGAN CHEM LAB,OXIDAT MECH SECT,BETHESDA,MD 20892. RP WEI, SJC (reprint author), RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,CANC RES LAB,PISCATAWAY,NJ 08855, USA. FU NCI NIH HHS [CA49756]; NIEHS NIH HHS [ES05022] NR 28 TC 72 Z9 73 U1 1 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 AUG PY 1994 VL 15 IS 8 BP 1729 EP 1735 DI 10.1093/carcin/15.8.1729 PG 7 WC Oncology SC Oncology GA PC325 UT WOS:A1994PC32500040 PM 8055656 ER PT J AU HOU, XY JOHNSON, AC ROSNER, MRR AF HOU, XY JOHNSON, AC ROSNER, MRR TI INDUCTION OF EPIDERMAL GROWTH-FACTOR RECEPTOR GENE-TRANSCRIPTION BY TRANSFORMING GROWTH-FACTOR-BETA-1 - ASSOCIATION WITH LOSS OF PROTEIN-BINDING TO A NEGATIVE REGULATORY ELEMENT SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID NUCLEAR FACTOR-I; FACTOR-BETA; TGF-BETA-1 INHIBITION; MOLECULAR-CLONING; EXPRESSION; PROMOTER; COLLAGEN; CELLS; FOS; IDENTIFICATION AB Transforming growth factor beta (TGF-beta) is a potent modulator of cell growth in many systems. In normal rat kidney fibroblasts, TGF-beta1 increases epidermal growth factor (EGF) receptor gene transcription and synergizes with EGF to stimulate growth in soft agar, a characteristic of the transformed phenotype. In order to identify the target of TGF-beta1 action, we have used a series of 5' deletion mutants of the EGF receptor promoter linked to a chloramphenicol acetyltransferase reporter gene (ERCAT). The TGF-beta response element(s) was localized to a cis-regulatory region which resides between positions -919 and -860 relative to the ATG translation initiation codon of the EGF receptor promoter. This 60-base pair region contains a repressor of the EGF receptor promoter and a TGF-beta inhibitory element that mediates TGF-beta1 suppression of transin/stromelysin gene transcription through binding of a Fos-containing protein complex. Cotransfection of c-fos, c-jun, or both expression vectors with the intact or 5'-deleted ERCAT constructs identified several Fos-responsive inhibitory regions within the EGF receptor promoter, but these did not localize to the -919 to -860 promoter region. Mobility shift assays showed binding of the 60-base pair DNA fragment to proteins in extracts from untreated normal rat kidney cells; the binding was specifically competed by oligonucleotides containing a CAGATG sequence but not by oligonucleotides containing the EGF receptor repressor or the TGF-beta inhibitory element. TGF-beta1 treatment but not anti-Fos antibody caused a decrease in specific 60-base pair DNA-protein complex formation. These results provide evidence for a model in which TGF-beta1 stimulates EGF receptor gene transcription through a Fos-independent mechanism involving loss of binding of proteins to the CAGATG element in the EGF receptor gene promoter. C1 UNIV CHICAGO,BEN MAY INST,5841 S MARYLAND AVE,BOX MC 6027,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 35541] NR 36 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1994 VL 5 IS 8 BP 801 EP 809 PG 9 WC Cell Biology SC Cell Biology GA PB149 UT WOS:A1994PB14900002 PM 7986746 ER EF