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Biomedical subjects

Y Cheng

Publications and source records attributed to Y Cheng.

At least 307 records · Page 17Linked to original sources
PubMed1983

Establishment of dihydrofolate reductase-increased human cell lines and relationship between dihydrofolate reductase levels and gene copy.

A series of methotrexate (MTX)-resistant human sublines developed by step increases in selected MTX concentrations have been cloned and examined for dihydrofolate reductase (DHFR) content, relative DNA copy number, and sensitivity to MTX. These cloned sublines had increased DHFR levels which were dependent on the presence of MTX in the medium. The increased levels of DHFR in the absence of MTX were stable in all the clones examined for over a year. Antibody immunolocalization on Western blots showed good correlation of the intensity of the immunostained DHFR band with enzyme activities. Relative gene copy number in these sublines was low relative to the DHFR increases and was not dependent on the presence of MTX in the medium. The increase in gene copy number in these sublines did not correlate with either the levels of DHFR or the sensitivity to MTX.

Animals↗
PubMed1982

Characterization of the DNA polymerases induced by a group of herpes simplex virus type I variants selected for growth in the presence of phosphonoformic acid.

Five independently derived variants of a herpes simplex virus type I (HSV-1) strain were plaque purified from a virus population passaged in 1 mM phosphonoformic acid (PFA). The DNA polymerase induced by the parent and PFA-resistant viruses were purified and characterized. No differences were observed among the enzymes with respect to their chromatographic properties, specific activities, or polypeptides resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The variant enzymes exhibited levels of PFA resistance which ranged from 15- to 25-fold. Resistance to PFA was always associated with a similar degree of resistance to its congener phosphonoacetic acid, but cross-resistance to beta-phenylphosphonoacetic acid was only seen with two of the five variant enzymes. PFA and pyrophosphate were mutually competitive in PPi exchange reactions, but in DNA synthetic reactions the levels of resistance to PFA and PPi were not equal. The apparent affinities of the enzymes for Mg2+ did parallel their affinities for PFA. Km values of dNTPs were about 2-fold higher than the parent virus enzyme for all of the variant enzymes except one which was 4-fold higher. The processivity of polymerization was apparently unaffected by the enzyme changes related to PFA resistance although one variant enzyme had a lower value. Resistance among the variant enzymes to the triphosphates of 9-(2-hydroxyethoxymethyl)guanine and 2',3'-dideoxyguanosine was directly related to the level of resistance to PFA. The data presented here indicated that (i) PFA resistance may result from several types of active site alterations, since the PFA-resistant enzymes were of three kinetically distinct types. Also, additional enzyme alterations, probably unrelated to PFA resistance, were detected in one enzyme. (ii) PFA and PPi possess some different binding determinants within the active center of herpes simplex virus type I DNA polymerase. (iii) PFA and the triphosphates of 9-(2-hydroxyethoxymethyl)guanine and 2',3'-dideoxyguanosine may have a common ultimate inhibitory mechanism.

Antiviral Agents↗
PubMed1982

Selective antiviral agents. The metabolism of 5-propyl-2'-deoxyuridine and effects on DNA synthesis in herpes simplex virus type 1 infections.

The metabolism and disposition of 5-propyl-2'-deoxyuridine (Pr-dUrd) in herpes simplex virus type 1 infections were investigated in cell culture using [14C]Pr-dUrd, [32P]orthophosphate, and several methods including high pressure liquid chromatography and isopycnic centrifugation. Results in infected cells indicate Pr-dUrd 1) is taken up and phosphorylated to mono-, di-, and triphosphates; 2) is incorporated into DNA; 3) preferentially inhibits synthesis of viral DNA; 4) blocks re-initiation of viral DNA synthesis even after removal of the nucleoside from the culture; and 5) exerts these effects early in the course of infection (before 6 h postinfection). Pr-dUrd was not phosphorylated in uninfected cells, and had little or no effect on apparent cellular DNA synthesis in infected or uninfected cells. Present evidence suggests one possible antiviral event could be the lethal effect of Pr-dUrd after incorporation into viral DNA by alteration of DNA template-directed functions such as replication.

Antiviral Agents↗
PubMed1980

Glycyl-L-histidyl-L-lysine, a growth promoting factor for human cells.

The growth promoting activity of a synthesis tripeptide, glycyl-L-histidyl-L-lysine (GHL) as a possible serum substitute was determined using human KB cells. GHL was found to stimulate the growth of human KB, and HeLa cells, but not WI-38 cells when employed in serum limited medium containing bovine serum albumin (BSA). The rate of growth of cells in this medium was similar to that of cells grown in medium containing 5% serum. While BSA did enhance slightly the growth of cells, its major function appeared to be in maintaining cellular viability. The growth promoting activity was specific for GHL; other synthetic peptides which were similar in composition had no activity, but they did interfere with the growth promoting activity of GHL. These observations suggest that by modifying GHL, analogues could be developed which might regulate cell growth and be useful in cancer chemotherapy.

Cell Division↗
PubMed1979

Human deoxyuridine triphosphate nucleotidohydrolase. Purification and characterization of the deoxyuridine triphosphate nucleotidohydrolase from acute lymphocytic leukemia.

A new fast assay procedure for increasing deoxyuridine triphosphate nucleotidohydrolase activity was developed. With this assay procedure, this enzyme derived from blast cells of patients with acute lymphocytic leukemia was purified at least 1218-fold. The molecular weight was estimated by gel filtration to be 43,000. The enzyme exhibited optimal activity over a pH range of 7 to 8 and the activation energy was estimated to be 6.5 kcal/mol at pH 7.5. While the enzyme had activity in the absence of added divalent cations, the activity could be inhibited by EDTA but not by phenanthroline. The inhibition caused by EDTA could be reversed by Mg2+ or Zn2+. The enzyme had maximal activity in the presence of Mg2+ (40 muM) and Mg2+ (4 mM) stabilized the enzyme at 37 degrees C. Cupric ion (0.5 mM) inhibited (50%) enzyme activity in the presence or absence of Mg2+. The substrate for the enzyme was dUTP and the apparent Km was 1 muM. No other deoxyribonucleoside or ribonucleoside triphosphate served as a substrate for the enzyme.

Cations, Divalent↗
PubMed1977

Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia.

Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography. The molecular weight was estimated by glycerol gradient centrifugation to be 50,000. This enzyme had an optimal activity at pH 7.1 and required a divalent cation in order to catalyze the reaction. Mg2+ and Mn2+ were found to be the preferential divalent cations. The activation energy was estimated to be 19.1 kcal/mol at pH 7.2. Initial velocity study suggested that the reaction followed a sequential mechanism. Mg2+ ATP had a Km of 0.25 mM and dTMP had a Km of 40 micrometer. The enzyme was unstable even at 4 degrees. In the presence of ATP or dTMP the enzyme maintained its activity. Purine triphosphate nucleosides were found to be better phosphate donors than the pyrimidine triphosphate nucleosides. ATP and dATP had a lower Km and a higher Vmax than GTP and dGTP. dTMP was the only preferred phosphate receptor among all the monophosphate nucleotides tested dTTP and IdUTP competed with both substrates and inhibited the reaction with a Ki of 0.75 mM and 1.1 mM, respectively.

Chromatography, Affinity↗
PubMed1977

Quantitative analysis of tubulin and microtubule compartments in isolated rat hepatocytes.

A combined morphometric and biochemical approach has been used to identify and quantitate microtubules and tubulin in isolated hepatocytes. The total soluble pool of microtubule protein was estimated by specific high affinity binding to radiolabeled colchicine. Scatchard analysis of the data identified two populations of binding sites: high affinity-low capacity sites resembling tubulin and low affinity-high capacity sites believed to represent nonspecific colchicine-binding sites. Data from these studies indicate that tubulin represents 1% of the soluble protein of the cell, that 9.0 X 10(-14) dimers of tubulin are present per microgram soluble hepatocyte protein, and that the average hepatocyte contains 3.1 X 10(7) tubulin dimers. Our calculations suggest that this amount of tubulin would form a microtubule 1.9 cm in length if totally assembled. However, stereological measurements indicate that the actual length of microtubules in the cytosolic compartment of the average hepatocyte is only 0.28 cm. Thus, these experiments suggest that only 15% of the available tubulin in hepatocytes of postabsorptive rats is assembled in the form of microtubules.

Animals↗
PubMedDate not supplied

Unusual liver MR findings of Wilson's disease in an asymptomatic 2-year-old girl.

We describe the unusual magnetic resonance (MR) findings of a case of Wilson's disease (WD) in an asymptomatic 2-year-old girl. Preenhanced computed tomography revealed multiple hyperdense areas in the liver. These lesions were hyperintense on T1-weighted and hypointense on T2-weighted MR images, results that might be ascribed to the paramagnetism of copper deposited in liver at a relatively early stage of the disease before severe liver cirrhosis had evolved.

Biopsy↗
PubMedDate not supplied

Summer and winter patterns of seasonality in Chinese college students: a replication.

The goal of this study is to replicate an earlier epidemiological finding of seasonal changes in mood and behavior among Chinese medical students using an independent study population. Three hundred nineteen college students were surveyed with a Chinese version of the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI) in Jining, China, during March of 1996. The frequency of seasonal patterns and prevalence rates of seasonal affective disorder (SAD) were estimated and compared with data from the medical student survey conducted in the same city. The mean Global Seasonality Score (GSS) of this college student sample was 9.9 +/- 4.9; 84% of the subjects reported some problems with the changing seasons. Summer difficulties were more prevalent than winter difficulties by a ratio of 1.9 to 1 (38.9% v 20.1%). The estimated rates of summer SAD and subsyndromal-SAD (s-SAD) were 7.5% and 11.9%, respectively, as compared with the corresponding winter figures of 5.6% and 6.3%. In addition, the prevalence estimates of winter pattern or winter SADs were higher in males than in females, but the corresponding summer figures showed no gender difference. Compared with the data from the medical student survey, this college student sample had a higher GSS (P < .01) but comparable summer to winter and female to male ratios for the prevalence of SADs (P > .05). These results replicate our previous findings that seasonal problems are common in China, but the predominant problems are summer difficulties rather than winter difficulties, and there is no female preponderance in the prevalence estimates of such problems. Both findings stand in contrast to most Western studies but are consistent with the only other published study performed in the Orient.

Adult↗
PubMedDate not supplied

Initial characterization of PMMA as a discriminative stimulus.

The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It has also been shown, however, that stimulus generalization does occur in animals trained to discriminate the designer drug MDMA ("Ecstasy" or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane) from vehicle. In order to further characterize this unique agent, we trained a group of six Sprague-Dawley rats to discriminate 1.25 mg/kg of PMMA (ED50 = 0.44 mg/kg) from saline vehicle. The PMMA stimulus failed to generalize to the phenylisopropylamine stimulant (+)amphetamine, or to the phenylisopropylamine hallucinogen DOM. Stimulus generalization occurred to (+/-)MDMA (ED50 = 1.32 mg/kg) and S(+)MDMA (ED50 = 0.48 mg/kg). Partial generalization occurred with R(+)MDMA, PMA, 3.4-DMA, and fenfluramine. The PMMA stimulus also generalized to the alpha-ethyl homolog of PMMA (EH/PMMA, ED50 = 1.29 mg/kg). Taken together, the results of these studies suggest that PMMA is an MDMA-like agent that lacks the amphetamine-like stimulant character of MDMA. These findings support our previous suggestion that PMMA be considered the structural parent of the MDMA-like family of designer drugs.

Animals↗
PubMedDate not supplied

Prevalence and correlates of sexual dysfunction among young adult married women in rural China: a population-based study.

The study investigates prevalence of sexual dysfunction (SD), sexual satisfaction and their correlates in the rural female population in China. An anonymous cross-sectional study was carried out in a random sample of 1178 married of age 20-39 years in Dengfeng County, Henan, China. The prevalence of having at least one SD was 43 and 38% of the respondents were satisfied with their sexual life; 64.0% thought that sex was not important to them; and 85.7% believed that they do not have adequate sex-related knowledge. Having SD and high sexual satisfaction were associated with high mental health or vitality quality of life scores and better perceived health status. Other independent predictors of SD included sociodemographic variables, biological variables, life style factors and masturbation. It is concluded that SD was prevalent among the studied women and were associated with mental health. The sexual health among married women needs to be improved in rural China.

Adult↗
PubMedDate not supplied

Co-occurrence of sexual dysfunction within young married couple dyads living in rural China: a population-based study.

A total of 298 randomly selected married couple dyads in rural China were studied. Sexual dysfunction (SD) was reported by 84 (28.2%) of the husbands and 136 (45.6%) of the wives. Co-occurrence of SD was reported by 51 of the married couples; hence, SD co-occurred in the spouses of 60.7% of the husbands with SD and 37.5% of wives reporting SD. Pain during intercourse but not other SD of the wives was associated with SD of the husbands. Men's SD including inability to achieve orgasm, finding sex not pleasurable and lack of interest in sex, but not premature ejaculation or erectile dysfunction, were associated with the presence of SD among the wives. Decision-making control on sexual matters, communication between the spouses on sexual problems, the seeking of professional help, perceived adequacy of sexual knowledge as well as mental health and vitality quality of life indices were associated with co-occurrence of SD within the couple dyads.

Adult↗