Search PubMed⌕ Search

Biomedical subjects

C Y Wang

Publications and source records attributed to C Y Wang.

At least 19 recordsLinked to original sources
PubMed1992

Evolutionarily conserved Ets family members display distinct DNA binding specificities.

Members of the Ets family of proto-oncogenes encode sequence-specific transcription factors that bind to a purine-rich motif centered around a conserved GGA trinucleotide. Ets binding sites have been identified in the transcriptional regulatory regions of multiple T cell genes including the T cell receptor alpha and beta (TCR-alpha and -beta) enhancers and the IL-2 enhancer, as well as in the enhancers of several T cell-trophic viruses including Maloney sarcoma virus, human leukemia virus type 1, and human immunodeficiency virus-2. T cells express multiple members of the Ets gene family including Ets-1, Ets-2, GABP alpha, Elf-1, and Fli-1. The different patterns of expression and protein-protein interactions of these different Ets family members undoubtedly contribute to their ability to specifically regulate distinct sets of T cell genes. However, previous studies have suggested that different Ets family members might also display distinct DNA binding specificities. In this report, we have examined the DNA binding characteristics of two Ets family members, Ets-1 and Elf-1, that are highly expressed in T cells. The results demonstrate that the minimal DNA binding domain of these proteins consists of adjacent basic and putative alpha-helical regions that are conserved in all of the known Ets family members. Both regions are required for DNA binding activity. In vitro binding studies demonstrated that Ets-1 and Elf-1 display distinct DNA binding specificities, and, thereby interact preferentially with different naturally occurring Ets binding sites. A comparison of known Ets binding sites identified three nucleotides at the 3' end of these sequences that control the differential binding of the Ets-1 and Elf-1 proteins. These results are consistent with a model in which different Ets family members regulate the expression of different T cell genes by binding preferentially to purine-rich sequences that share a GGA core motif, but contain distinct flanking sequences.

Amino Acid Sequence↗
PubMed1992

Phorbol ester-induced hairy cell features on chronic lymphocytic leukemia cells in vitro.

Leukemic cells from eight patients with chronic lymphocytic leukemia were isolated and cultured in the continuous presence of 12-O-tetradecanoylphorbol 13-acetate (TPA) at a concentration of 1.6 x 10(-9) M for 4-10 days. Aliquots of cells were then analyzed at intervals of 24-72 hr for changes in morphology, acid phosphatase staining (AP), and expression of two hairy cell-associated surface antigens, HCL1 (CD22, Leu 14) and HCL3 (CD11c, Leu M5). All cases studied showed typical B-CLL phenotype, and only a small proportion of cells expressed CD22 and CD11c (mean 7% and 4.9%, respectively). TPA treatment induced the coexpression of CD22 (mean 49%) and CD11c (mean 48%) and tartrate-resistant acid phosphatase in seven of eight cases. Morphologically, cells in TPA cultures expressed hairy cell features that were evident in light and electron microscopic studies. Collectively these changes indicate that TPA can induce hairy cell features on CLL cells in vitro, suggesting the later maturational stage of HCL compared with CLL.

Acid Phosphatase↗
PubMed1992

Effect of acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione on 2-acetylaminofluorene-induced glutathione S-transferase positive foci in the rat liver.

Acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (TFPB), 1-benzoyl-2-trifluoromethyl-2-acetoxyethene (BTAE), and 1-benzoyl-2-trifluoromethyl-2-(4-methylthio)benzoyloxyethene (BTME), were synthesized and investigated for inhibition of tRNA binding by N-acetoxy-2-acetylaminofluorene (N-AcO-AAF), and induction of glutathione S-transferase placental form (GST-P) positive foci in the rat liver by 2-acetylaminofluorene (2-AAF). Male F344 rats were given BTAE or BTME intraperitoneally and 2-AAF by intragastric intubation. Two weeks following the treatment, the rats were maintained on the diet containing 0.05% phenobarbital for an additional 6 weeks and then killed. Development of GST-P positive foci was not affected by concomitant treatment with BTAE or BTME. These two compounds inhibited the in vitro binding of N-AcO-AAF to tRNA. Thus, although these diacylmethane derivatives had the in vitro inhibitory activity, they did not inhibit tumor-initiating activity of 2-AAF in the rat liver.

2-Acetylaminofluorene↗
PubMed1992

Chemical carcinogenesis of the urinary bladder--a status report.

Cigarette smoking and certain types of occupational exposure to arylamines appear to be the main cause of human urinary bladder cancer. Little is known of the promotion of bladder cancer in humans, although this stage has been demonstrated in rodents. Perhaps as a consequence of initiation, multifactorial alterations of cellular genes occur. These genes include the epidermal growth factor receptor gene, erbB-2, int-2, hst, and H-ras, which exert positive control over cell growth, as well as the suppressor genes Rb-1, and the gene coding for p53. Chromosomal changes such as deletions, translocations and/or amplifications related to these genes may be of significance for prognosis of this disease.

Animals↗
PubMed1992

Computationally efficient algorithms for convection-permeation-diffusion models for blood-tissue exchange.

Analysis of data on tissue depositions obtained by positron tomographic or NMR imaging, or of multiple tracer outflow dilution curves, requires fitting data with models composed of aggregates of capillary-tissue units. These units account for heterogeneities of flows and multisolute exchanges between longitudinally distributed regions across capillary and cell barriers within an organ. Because the analytic solutions to the partial differential equations require convolution integration, solutions are obtained relatively efficiently by a fast numerical method. Our approach centers on the use of a sliding fluid element algorithm for capillary convection, with the time step set equal to the length step divided by the fluid velocity. Radial fluxes by permeation between plasma, interstitial fluid, and cells and axial diffusion exchanges within each time step are calculated analytically. The method enforces mass conservation unless there is regional consumption. Solution for a 2-barrier, 3-region model, accurate to within 0.5%, are 100 to 1000 times faster than the corresponding, purely analytic solution, and over 10,000 times for a 4-region model. Applications include multiple indicator dilution studies of kinetics of transcapillary exchange and positron emission tomographic studies of the mechanisms of substrate transport into cells of organs in vivo.

Algorithms↗
PubMed1992

Posttransfusion hepatitis revisited by hepatitis C antibody assays and polymerase chain reaction.

Sera of 40 patients with posttransfusion non-A, non-B hepatitis were tested for hepatitis C and B viral genomes by polymerase chain reaction and for hepatitis C antibodies by synthetic peptide immunoassays. Five were then considered to have chronic hepatitis before transfusion. Six patients without hepatitis C markers and hepatitis B virus DNA recovered. In 29 recipients who became positive for hepatitis C virus RNA, posttransfusion hepatitis C was diagnosed. Of them, 5 were hepatitis B surface antigen carriers. Synthetic peptide immunoassays detected 28 whereas anti-C100 assay detected 23 of the 29 acute hepatitis C patients. Anticapsid antibody appeared earlier than the antinonstructural antibody in 10 seroconverters. They appeared simultaneously in 15 seroconverters but anticapsid antibody appeared later then the antinonstructural antibody in 3 hepatitis B carriers. Transient suppression of hepatitis B surface antigenemia was found in 2, whereas elevated hepatitis B virus DNA was found in 3 carriers during acute hepatitis C superinfection. In 2 carriers whose hepatitis C became chronic, both hepatitis B and C viral genomes persisted throughout 2 years of followup. Therefore these assays define posttransfusion hepatitis C more precisely, and there seems no significant interference between chronic hepatitis B and C virus infections.

Adult↗
PubMed1992

Hepatitis C and B viruses in hepatitis B surface antigen-negative hepatocellular carcinoma.

The relative role of hepatitis C virus and hepatitis B virus in hepatitis B surface antigen-negative hepatocellular carcinoma was evaluated by polymerase chain reaction in 31 patients from Taiwan. Twenty-one were positive for antibody to hepatitis C virus (group 1) and 10 were negative (group 2). Of the group 1 patients, hepatitis C viral RNA was detected in the serum by polymerase chain reaction in 16 and in the liver tissue in 17, whereas hepatitis B viral DNA was found in the liver tissue in only 4, and none were found in the serum. In group 2 patients, hepatitis C viral RNA was detected in the serum of 1 and in the liver tissue of another. In contrast, hepatitis B viral DNA was found in the serum of 4 patients and in the liver tissues of 5. It was concluded that hepatitis C virus plays an important role in hepatocarcinogenesis in hepatitis B surface antigen-negative patients in Taiwan, especially in those who had antibody to hepatitis C virus; in those without antibody to hepatitis C virus, hepatitis B virus might still be associated with the development of hepatocellular carcinoma in a significant proportion of such patients.

Adult↗
PubMed1992

Characterization of sequence changes in kinetoplast DNA maxicircles of drug-resistant Leishmania.

We have compared kinetoplast DNA maxicircles of tunicamycin- and arsenite-resistant variants of repeatedly cloned Leishmania mexicana amazonensis showing DNA amplification with wild-type and arsenite-resistant variants of the same lineage that do not show DNA amplification. DNA restriction patterns and the degree of cross-hybridization between maxicircle DNA fragments of parasites displaying DNA amplification and those of parasites without amplification were examined. In addition, the nucleotide sequence of the cytochrome b (Cyb) gene from the coding region was compared between these two groups of parasites. Extensive changes were found in the nucleotide sequences and the amino acid sequences of the cytochrome gene of the maxicircles of variants with DNA amplification. The Cyb genes from both groups had much shorter open reading frames than the same gene from Leishmania tarentolae and Trypanosoma brucei. The simultaneous changes in maxicircles and minicircles of these variants suggest that they may confer the advantage of maintaining viable mitochondrial function under selective pressure.

Amino Acid Sequence↗
PubMed1992

A MAb-based ELISA for detecting circulating antigen in CSF of patients with neurocysticercosis.

A monoclonal antibody (MAb)-based enzyme-linked immunosorbent assay (ELISA) was evaluated for detecting circulating antigen (CAg) in the cerebrospinal fluid (CSF) of patients with neurocysticercosis. CAg of Cysticercus Cellulosae was detected in 95 out of 116 patients with neurocysticercosis. Of the 21 neurocysticercosis patients in whom CAg was not detected, 14 had only higher density spots, 3 had one or two lower density spots and 4 had no obvious damage in their brain Computed Tomography (CT) scans. CAg was also not detected in CSF samples of patients with other diseases of the central nervous system. These included cerebral tumor, encephalopyosis, brain trauma, viral meningitis and cerebral hemorrhage. Detecting CAg with MAb-based ELISA is better than any previously available methods for the diagnosis of active neurocysticercosis.

Animals↗
PubMed1992

Purification and characterization of rat hepatic microsomal N,O-acyltransferases.

Hepatic microsomes of female F344 rats were capable of N,O-acyltransfer of N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) and N-hydroxy-N-formyl-2-aminofluorene (N-OH-FAF), N-deacetylation of N-OH-AAF and N-acetyl-2-aminofluorene (2-AAF), and O-deacetylation of 4-nitrophenyl acetate (NPA). The activity for N,O-acyltransfer of N-OH-FAF was approximately 20 times greater than that of N-OH-AAF. These microsomal activities were inducible by phenobarbital and were inhibitible by paraoxon. Four distinct N,O-acyltransferases were purified from solubilized hepatic microsomes of phenobarbital pretreated rats. These enzymes were purified to homogeneity, as judged by SDS-PAGE and analytical IEF. Their pIs were approximately 5.0, 5.5, 6.0 and 6.5 and their mol. wts were approximately 60, 61, 180 (a homotrimer of 59 kDa) and 60 kDa respectively. All the enzymes catalyzed the N,O-acyltransfer of N-OH-FAF, the N-deacetylation of N-OH-AAF and 2-AAF and the O-deacetylation of NPA. Among these four enzymes, the hydrolysis of NPA was best catalyzed by pI 6.5 protein, of 2-AAF by the pI 5.5 protein, and of N-OH-AAF by the pI 5.0 protein. The pI 5.5 and pI 6.5 proteins were equally active for N,O-acyltransferase and were more active than the other enzymes. The present study demonstrates that rat hepatic microsomal activities of N,O-acyltransfer, N-deacetylation and O-deacetylation are attributable to the same enzymes.

Acyltransferases↗
PubMed1992

A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells.

Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are structurally related retroviruses which both cause AIDS in humans. Although both viruses establish latency in quiescent human-peripheral-blood T cells, the asymptomatic phase of HIV-2 infection may be more prolonged than that of HIV-1. The latent phases of both HIV-1 and HIV-2 infection have been shown to be disrupted by T-cell activation, a process that requires host cell transcription factors. In the case of HIV-1, the transcription factor NF-kappa B is sufficient for inducible transcriptional activation. In contrast, factors in addition to NF-kappa B are required to activate HIV-2 transcription in infected T cells. In this report, we demonstrate that a novel Ets-related transcription factor, Elf-1, binds specifically to two purine-rich motifs in the HIV-2 enhancer. Mutagenesis experiments demonstrated that these Elf-1 binding sites are required for induction of HIV-2 transcription following T-cell-receptor-mediated T-cell activation. Moreover, Elf-1 is the only factor present in activated T-cell nuclear extracts that binds to these sites in electrophoretic mobility shift assays. Thus, Elf-1 is a novel transcription factor that appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression. These results may explain differences in the clinical spectra of diseases caused by HIV-1 and HIV-2 and may also have implications for the design of therapeutic approaches to HIV-2 infection.

Adult↗
PubMed1992

cis-acting sequences required for inducible interleukin-2 enhancer function bind a novel Ets-related protein, Elf-1.

The recent definition of a consensus DNA binding sequence for the Ets family of transcription factors has allowed the identification of potential Ets binding sites in the promoters and enhancers of many inducible T-cell genes. In the studies described in this report, we have identified two potential Ets binding sites, EBS1 and EBS2, which are conserved in both the human and murine interleukin-2 enhancers. Within the human enhancer, these two sites are located within the previously defined DNase I footprints, NFAT-1 and NFIL-2B, respectively. Electrophoretic mobility shift and methylation interference analyses demonstrated that EBS1 and EBS2 are essential for the formation of the NFAT-1 and NFIL-2B nuclear protein complexes. Furthermore, in vitro mutagenesis experiments demonstrated that inducible interleukin-2 enhancer function requires the presence of either EBS1 or EBS2. Two well-characterized Ets family members, Ets-1 and Ets-2, are reciprocally expressed during T-cell activation. Surprisingly, however, neither of these proteins bound in vitro to EBS1 or EBS2. We therefore screened a T-cell cDNA library under low-stringency conditions with a probe from the DNA binding domain of Ets-1 and isolated a novel Ets family member, Elf-1. Elf-1 contains a DNA binding domain that is nearly identical to that of E74, the ecdysone-inducible Drosophila transcription factor required for metamorphosis (hence the name Elf-1, for E74-like factor 1). Elf-1 bound specifically to both EBS1 and EBS2 in electrophoretic mobility shift assays. It also bound to the purine-rich CD3R element from the human immunodeficiency virus type 2 long terminal repeat, which is required for inducible virus expression in response to signalling through the T-cell receptor. Taken together, these results demonstrate that multiple Ets family members with apparently distinct DNA binding specificities regulate differential gene expression in resting and activated T cells.

Adult↗
PubMed1992

Synthesis of dibenzoylmethane derivatives and inhibition of mutagenicity in Salmonella typhimurium.

Twenty dibenzoylmethanes with methyl, methoxy, bromo, chloro, or fluoro substitution on either one or both benzene rings were synthesized and assayed for inhibition of the mutagenicity of 2-nitrofluorene in S. typhimurium TA98. 2,2-Dimethoxy, 3,3-dimethoxy and 3,3,4,4-tetramethoxydibenzoylmethane was as active as dibenzoylmethane. None of the halogen-substituted dibenzoylmethanes were active. These results demonstrate that dibenzoylmethanes can inhibit the mutagenicity of 2-nitrofluorene, and that modifications made on the benzene rings of dibenzoylmethane cannot enhance the antimutagenicity of this parent compound.

Antimutagenic Agents↗
PubMed1992

Purification and characterization of hamster hepatic microsomal N,O-acetyltransferase.

A microsomal N,O-acetyltransferase which activates carcinogenic arylacetohydroxamic acids was purified 75-fold from hamster liver sequentially by anion exchange column chromatography, chromatofocusing, gel filtration, and hydroxyapatite column chromatography. The purified enzyme, AT-2, was a glycoprotein with a molecular weight of 60000 and a pI value of 5.4. The N-terminal amino acid sequence of AT-2 was: 60000 and a pI value of 5.4. The N-terminal amino acid sequence of AT-2 was: Asp-Ser-Pro-Ser-Pro-Ile-Arg-Asn-Thr-His-Thr-Gly-Gln-Val-Arg-Gly-Leu-Val- His- Lys-. This sequence was highly homologous to that of the form 2 carboxylesterase of rabbit liver, but not to that of major hepatic microsomal carboxylesterases of hamster and other species. AT-2 catalyzed the hydrolysis of 4-nitrophenyl acetate and the N,O-acetyltransfer of N-hydroxy-2-acetylaminofluorene. Both enzyme activities were strongly inhibited by paraoxon, but not by iodoacetamide. These results demonstrate that this N,O-acetyltransferase is a member of carboxylesterase (EC 3.1.1.1).

Acetyltransferases↗
PubMed1992

Going deep into chemical burns.

This is a five year retrospective study of chemical burn injury in our burn center between 1 January 1987 and 31 December 1991. Of the 1,226 total burn cases, 131 patients had chemical burns. We noted a constant prevailing incidence of 10.7% per year. Males (72%) are more common than females (28%). Most of those injured are in the working age group (65%). Majority of cases had deep full thickness burn involving less than 10% of their total body surface area. Sulfuric acid is the most common chemical agent encountered. We had three mortality cases with deep third degree burns covering 60% of their total body surface area. Some clinical cases are demonstrated. Lastly, proposed solutions for the prevention of chemical burns are cited.

Accidents, Occupational↗