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Biomedical subjects

Q Dong

Publications and source records attributed to Q Dong.

At least 109 records · Page 6Linked to original sources
PubMed1996

Repair analysis of 4-hydroperoxycyclophosphamide-induced DNA interstrand crosslinking in the c-myc gene in 4-hydroperoxycyclophosphamide-sensitive and -resistant medulloblastoma cell lines.

Cyclophosphamide is one of the most active agents in the treatment of medulloblastoma. However, development of resistance to this alkylator frequently occurs and is the harbinger of tumor progression and death. In order to understand the biochemical basis of this resistance, we generated a panel of medulloblastoma cell lines in our laboratory that were resistant to 4-hydroperoxycyclophosphamide (4-HC). Previously, we have shown that elevated levels of aldehyde dehydrogenase and glutathione mediate cellular resistance to 4-HC. The present study was conducted to identify the third unknown mechanism mediating the resistance of cell line D283 Med (4-HCR) to 4-HC, testing the hypothesis that this resistance is mediated by an increased repair of DNA interstrand crosslinks (ICLs). The doses of 4-HC that produced a one- and two-log cell kill of D283 Med cells were 25 and 50 microM, respectively, compared with values of 125 and 165 microM in D283 Med (4-HCR), the resistant cell line. The formation and disappearance of 4-HC-induced DNA ICLs at the c-myc gene were subsequently studied by DNA denaturing/renaturing gel electrophoresis and Southern blot analysis. 4-HC-induced DNA ICLs in the c-myc gene exhibited a dose-dependent relationship. The percentage of the c-myc gene that was crosslinked was approximately 1-3% at a dose of 100 microM. More than 50% of the DNA crosslinking in D283 Med (4-HCR) cells was removed by 6 h after drug treatment, whereas, in D283 Med cells, more than 90% of the DNA crosslinking was still present at 6 h. These findings suggest that the increased repair of DNA ICLs in D283 Med (4-HCR) may contribute significantly to its resistance to 4-HC.

Blotting, Southern↗
PubMed1996

The rate and pattern of alcohol consumption among Chinese adolescents.

OBJECTIVE: To assess the prevalence and pattern of alcohol consumption and its relation to participation in other social activities and problem behaviors among adolescents residing in the People's Republic of China. METHODS: Data were collected from a sample of 1,040 students in 6th, 8th, and 10th grades from five public schools in Beijing, China by using a self-administered questionnaire. Chi-square statistics and two-way ANOVA were used to assess the gender and grade difference in lifetime alcohol use of various alcoholic beverages. The age-adjusted and grade-adjusted odds ratio was used to assess the association between alcohol use and selected social activities and problem behaviors. RESULTS: Approximately 70% of the study sample reported prior alcohol consumption. The rate of drinking among males was significantly higher than among females (78% vs. 61%, p < .00001), and the rates among both genders increased with advancing grade (54%, 72%, and 84%, respectively, p < .001). Beer was the most commonly consumed alcoholic beverage. The results also suggested a progression from beer to wine and/or liquor. Drinking behavior was positively associated with participation in unstructured social activities and other problem behaviors. CONCLUSIONS: Alcohol use was prevalent among adolescents residing in China. The findings underscore the need for and importance of intervention efforts targeting alcohol consumption among early adolescents in China.

Adolescent↗
PubMed1996

Analysis of impact of rigid projectiles on compound targets.

We developed a model to simulate a person, with and without protective armor, being subjected to an impact of a high speed, rigid projectile. The complex nature of the head and chest are simulated in our layered, spaced, various thickness targets made of different materials. A rigid projectile-target interaction model is described. Target resistance force was obtained from a generalized Poncelet equation. Good agreement between observed and computed penetration phenomena was obtained.

Computer Simulation↗
PubMed1996

Fears in American, Australian, Chinese, and Nigerian children and adolescents: a cross-cultural study.

The fears of childhood and adolescence may differ from one cultural context to another. We explored this possibility in 1200 American, Australian, Chinese, and Nigerian children and adolescents between 7 and 17 years of age. Responses to a standard fear survey schedule revealed significant differences in the number, content, pattern, and level of fears. Nigerian children and adolescents endorsed fears at higher levels than American, Australian, or Chinese youth who did not differ from one another. However, differences in the pattern and content of fears for boys and girls of different ages were noted across the countries. Results were interpreted within a cultural context, which suggested that cultures which favor inhibition, compliance, and obedience serve to increase levels of fear. Alternative interpretations are offered and limitations of cross-cultural research are explored.

Adolescent↗
PubMed1996

Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s, or thyrotropin-releasing hormone receptor genes.

Activating mutations encoding substitutions at positions Arg201 and Gln227 of the alpha-subunit of the stimulatory G protein. G10 have been found in about 40% of pituitary somatotroph tumors. Although the etiology of thyrotroph adenomas is unknown, their autonomous behavior and blunted response to stimulatory hypothalamic hormone superficially resemble those of somatotroph tumors. We hypothesized that a subset of thyrotroph tumors might be caused by dominant somatic mutations that lead to inappropriate activation of the Gq/phospholipase C beta/Ca2+/protein kinase C. pathway normally triggered by occupancy of the TRH receptor (TRHR). We, therefore, screened samples from nine thyrotroph tumors for the presence of activating mutations of the alpha q, alpha 11, and TRHR genes. Fragments of alpha q and alpha 11 complementary DNA encompassing residues (Arg183 and Gln209) that correspond to Arg201 and Gln227 of alpha q were amplified and sequenced. Temperature gradient gel electrophoresis was used to screen for heterozygous mutations in the TRHR coding sequence as well as for known alpha s mutations. No mutations were detected. We conclude that mutations in these regions of the alpha q, alpha 11, alpha s, and TRHR genes occur infrequently, if at all, in human thyrotroph tumors. Alternative mechanisms underlying thyrotroph tumorigenesis, including changes in the expression levels of G protein alpha-subunits or TRHR, dysregulation of downstream components, inappropriate activation of other stimulatory pathways, or loss of inhibitory inputs, remain to be explored.

Adult↗
PubMed1995

A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5'-d(GAC).

Phosphoramide mustard-induced DNA interstrand cross-links were studied both in vitro and by computer simulation. The local determinants for the formation of phosphoramide mustard-induced DNA interstrand cross-links were defined by using different pairs of synthetic oligonucleotide duplexes, each of which contained a single potentially cross-linkable site. Phosphoramide mustard was found to cross-link dG to dG at a 5'-d(GAC)-3'. The structural basis for the formation of this 1,3 cross-link was studied by molecular dynamics and quantum chemistry. Molecular dynamics indicated that the geometrical proximity of the binding sites also favored a 1,3 dG-to-dG linkage over a 1,2 dG-to-dG linkage in a 5'-d(GCC)-3' sequence. While the enthalpies of 1,2 and 1,3 mustard cross-linked DNA were found to be very close, a 1,3 structure was more flexible and may therefore be in a considerably higher entropic state.

Base Sequence↗
PubMed1995

Molecular cloning of human G alpha q cDNA and chromosomal localization of the G alpha q gene (GNAQ) and a processed pseudogene.

G alpha q is the alpha subunit of one of the heterotrimeric GTP-binding proteins that mediates stimulation of phospholipase C beta. We report the isolation and characterization of cDNA clones from a frontal cortex cDNA library encoding human G alpha q. The encoded protein is 359 amino acids long and is identical in all but one amino acid residue to mouse G alpha q. Analysis of human genomic DNA reveals an intronless sequence with strong homology to human G alpha q cDNA. In comparison to G alpha q cDNA, this genomic DNA sequence includes several small deletions and insertions that alter the reading frame, multiple single base changes, and a premature termination codon in the open reading frame, hallmarks of a processed pseudogene. Probes derived from human G alpha q cDNA sequence map to both chromosomes 2 and 9 in high-stringency genomic blot analyses of DNA from a panel of human-rodent hybrid cell lines. PCR primers that selectively amplify the pseudogene sequence generate a product only when DNA containing human chromosome 2 is used as the template, indicating that the authentic G alpha q gene (GNAQ) is located on chromosome 9. Regional localization by FISH analysis places GNAQ at 9q21 and the pseudogene at 2q14.3-q21.

Animals↗
PubMed1995

Mutational studies of human DNA polymerase alpha. Lysine 950 in the third most conserved region of alpha-like DNA polymerases is involved in binding the deoxynucleoside triphosphate.

The function of a lysine residue, Lys950, of human DNA polymerase alpha located in the third most conserved region and conserved in all of the alpha-like polymerases was analyzed by site-directed mutagenesis. Lys950 was mutagenized to Arg, Ala, or Asn. The mutant enzymes were expressed in insect cells infected with recombinant baculoviruses and purified to near homogeneity. The mutant enzymes had specific activities ranging from 8 to 22% of the wild type. All three Lys950 mutants utilized Mn2+ as metal activator more effectively than the wild type enzyme and showed an increase in Km values for deoxynucleoside triphosphate but not k(cat) values in reactions with either Mg2+ or Mn2+ as the metal activator. Although mutation of the Lys950 residue caused an increase in Km values for deoxynucleoside triphosphates, mutations of Lys950 to Arg, Ala, or Asn did not alter the mutant enzymes' misinsertion efficiency in reactions with Mg2+ as a metal activator as compared with that of the wild type, suggesting that the base of the incoming deoxynucleoside triphosphate is not the structural feature interacting with the Lys950 side chain. In reaction with Mn2+ as a metal activator, all three Lys950 mutants had an improved fidelity for deoxynucleotide misinsertion compared to wild type. Inhibition studies of the three Lys950 mutant derivatives with an inhibitor, structural analogs of deoxynucleoside triphosphate, and pyrophosphate suggest that the deoxyribose sugar and beta-,gamma-phosphate groups are not the structural feature recognized by the Lys950 side chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Interaction of herpes simplex virus 1 origin-binding protein with DNA polymerase alpha.

The herpes simplex virus 1 (HSV-1) genome encodes seven polypeptides that are required for its replication. These include a heterodimeric DNA polymerase, a single-strand-DNA-binding protein, a heterotrimeric helicase/primase, and a protein (UL9 protein) that binds specifically to an HSV-1 origin of replication (oris). We demonstrate here that UL9 protein interacts specifically with the 180-kDa catalytic subunit of the cellular DNA polymerase alpha-primase. This interaction can be detected by immunoprecipitation with antibodies directed against either of these proteins, by gel mobility shift of an oris-UL9 protein complex, and by stimulation of DNA polymerase activity by the UL9 protein. These findings suggest that enzymes required for cellular DNA replication also participate in HSV-1 DNA replication.

Animals↗
PubMed1995

Perceptions of fear in other children and adolescents: the role of gender and friendship status.

Gender differences in fear were examined in 693 Chinese children and adolescents. Subjects were asked to rate their own fears, the fears of their best friends, and the fears of "other" classmates using the Fear Survey Schedule for Children--Revised (Ollendick, 1983). Consistent with previous investigations in Western and Eastern countries, girls rated themselves as more fearful than boys. In addition, both girls and boys rated their best friends as similar in number, content, and intensity of fears. However, girls rated their classmates as less fearful than themselves or their best friends, while boys rated their classmates as more fearful then themselves or their best friends. Findings are discussed in terms of gender role expectations and similarity-attraction hypotheses.

Adolescent↗
PubMed1995

The czc operon of Alcaligenes eutrophus CH34: from resistance mechanism to the removal of heavy metals.

The plasmid-borne czc operon ensures for resistance to Cd2+, Zn2+ and Co2+ ions through a tricomponent export pathway and is associated to various conjugative plasmids of A. eutrophus strains isolated from metal-contaminated industrial areas. The czc region of pMOL30 was reassessed especially for the segments located upstream and downstream the structural genes czc CBA. In cultures grown with high concentrations of heavy metals, czc-mediated efflux of cations is followed by a process of metal bioprecipitation. These observations led to the development of bioreactors designed for the removal of heavy metals from polluted effluents.

ATP-Binding Cassette Transporters↗
PubMed1995

Antithrombotic agents: from RGD to peptide mimetics.

This review covers the recent advances in the development of highly potent inhibitors of platelet aggregation as potential therapeutic drugs for thrombosis related to cardiovascular and cerebrovascular diseases. The discovery of RGD sequence-directed cell surface receptors (the integrins) has led to extensive research in the development of small RGD containing peptides and their mimetics as antithrombotic agents. These agents work by inhibiting platelet aggregation through competitive blocking of fibrinogen to the platelet surface receptor, GPIIb/IIIa. The pharmacophoric nature of the aspartic acid and arginine side chains of the RGD unit has allowed the development of strategies for rational design, largely based on assumed bioactive RGD conformations and lead optimization. Applications of such strategies, from RGD peptides to peptide hybrids and then to non-peptide mimetics, are described. Also discussed is the important issue of specificity toward GPIIb/IIIa, keeping in view that the RGD unit is a key recognition signal for a variety of cell surface receptors.

Amino Acid Sequence↗
PubMed1995

The stability and prediction of fears in Chinese children and adolescents: a one-year follow-up.

The stability in number, level, content, and pattern of fears over a one-year period was examined in Chinese children and adolescents aged 7-17. In addition, perceptions of fear in friends and parents as well as perceptions of the controllability and modifiability of fears were explored as predictors of subsequent fear level. Evidence for moderate stability of fears was obtained. However, stability was qualified by age and sex interaction effects. A developmental-cultural hypothesis was put forth to account for those findings. Hierarchical regression analyses revealed that perceptions of fears in friends and parents, along with perceptions of the controllability and modifiability of fears, were predictive of fear level at follow-up. Limitations of the study are noted.

Adolescent↗
PubMed1995

Only children and children with siblings in the People's Republic of China: levels of fear, anxiety, and depression.

In 1979, China implemented its one-child-per-family policy in order to control its burgeoning population. Subsequently, concern has been raised about the policy and its potentially negative effects on children. In the present study, we examined these presumed effects on 202 adolescents born before the policy went into effect, 290 preadolescents born during the period in which the policy was being implemented, and 239 children who were born after the policy went into effect. Measures of fear, anxiety, and depression were obtained. Contrary to our hypotheses, based on concerns raised by the one-child policy, children with siblings reported significantly higher levels of fear, anxiety, and depression than only children, regardless of when they were born. For depression, this effect was qualified by a sibling status x age interaction. Children with siblings born after the policy went into effect, or during its implementation, reported higher levels of depression than did only children; however, only children and children with siblings born before the policy went into effect did not differ significantly from one another. Sociocultural factors associated with these findings are explored.

Adolescent↗
PubMed1994

Characterization of the activating region of Escherichia coli catabolite gene activator protein (CAP). I. Saturation and alanine-scanning mutagenesis.

It has been proposed that the surface loop consisting of amino acid residues 152 to 166 of the catabolite gene activator protein (CAP) of Escherichia coli makes direct protein-protein contact with RNA polymerase at the lac promoter. In this work, we have used targeted saturation mutagenesis of codons 152 to 166 of the gene encoding CAP, followed by a screen, to isolate more than 200 independent mutants of CAP defective in transcription activation but not defective in DNA binding. All isolated single-substitution mutants map to just eight amino acid residues; 156, 157, 158, 159, 160, 162, 163 and 164. We propose that these residues define the full extent of the epitope on CAP for the proposed CAP-RNA polymerase interaction. In addition, we have constructed alanine substitutions at each position from residue 152 to 166 of CAP, and we have analyzed the effects on transcription activation at the lac promoter and on DNA binding. Alanine substitution of Thr158 results in an approximately eightfold specific defect in transcription activation. In contrast, alanine substitution of no other residue tested results in a more than twofold specific defect in transcription activation. We conclude that, for Thr158, side-chain atoms beyond C beta are essential for transcription activation at the lac promoter, and we propose that Thr158 OH7 gamma makes direct contact with RNA polymerase in the ternary complex of lac promoter, CAP and RNA polymerase. We conclude further that for no residue other than Thr158 are side-chain atoms beyond C beta essential for transcription activation at the lac promoter.

Alanine↗