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Biomedical subjects

Q Zhou

Publications and source records attributed to Q Zhou.

At least 181 records · Page 10Linked to original sources
PubMed1999

CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin.

OBJECTIVES: Omeprazole is metabolized mainly by CYP2C19 which has two major mutations (CYP2C19*2 in exon5 and CYP2C19*3 in exon4) associated with the poor metabolizer (PM) phenotype. The aim of this study was to examine the relationship between genetic polymorphism of CYP2C19 and metabolism of omeprazole administrated as a single dose or as repeated-doses, which were in both cases co-administered with clarithromycin. METHODS: Twelve healthy Japanese subjects were typed for CYP2C19 polymorphism. In the single-dose study, plasma levels of omeprazole and its metabolites were measured for 24 h after administration of 20 mg omeprazole and 400 mg clarithromycin to six healthy Japanese subjects. In the repeated-dose study, plasma levels of omeprazole and its metabolites were measured after repeated oral administration of 20 mg omeprazole and 400 mg clarithromycin twice daily for 6 days and then after 20 mg omeprazole and 400 mg clarithromycin once on the 7th day to the other 6 healthy Japanese subjects. RESULTS: In the single-dose study, the areas under the plasma concentration-versus-time curve (AUCs) of omeprazole of homozygotes for the wild-type allele (*1/*1 n = 2), heterozygotes (n = 3) for the CYP2C19*2 (*1/ *2) or for the CYP2C19*3 (*1/*3) and heterozygote (n = 1) for the two defects (*2/*3) were on average 450, 1007 and 6710 ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, *1/*2 or *1/*3 and *2/*3 were 1, 2 and 30, respectively. In the repeated-dose study, the AUCs of omeprazole for * 1/ *1, *1/*2 or *1/*3 and *2/*3 were 4041 (n = 2), 3149 (n = 3) and 6684 (n = 1) ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, * 1/*2 or * 1/*3 and *2/*3 were7, 11 and 30, respectively. In the repeated-dose study, the AUC of omeprazole of * 1/*1 genotypes was nine-fold higher, that of *1/*2 and *1/*3 genotypes was three-fold higher, and the Cmax value of omeprazole was three-fold higher compared with subjects with the same genotype in the single-dose study. However, there were few differences in the AUC and Cmax of omeprazole between the *2/*3 genotype in the single-dose study and the homozygote for the CYP2C19*2 (*2/*2) in the repeated-dose study. CONCLUSION: Subjects with *1/*1, *1/*2 and *1/*3 genotypes in the repeated-dose study had lower CYP2C19 activity than subjects of the same genotype in the single-dose study. The difference in omeprazole metabolism between subjects with different genotypes observed on day 1 seemed to disappear after 7 days of repeated-dose administration.

Adult↗
PubMed1999

Dephosphorylation increases insulin-stimulated receptor kinase activity in skeletal muscle of obese Zucker rats.

Serine/threonine phosphorylation of insulin receptor has been implicated in the development of insulin resistance. To investigate whether dephosphorylation of serine/threonine residues of the insulin receptor may restore the decreased insulin-stimulated receptor tyrosine kinase activity in skeletal muscle of obese Zucker rats, insulin receptor tyrosine kinase activity was measured before and after alkaline phosphatase treatment. Compared to lean controls, insulin-stimulated glucose transport was depressed by 61% (p < 0.05) in obese Zucker rats. The insulin receptor and insulin receptor substrate-1 contents were decreased by 14% (p < 0.05) and 16% (p < 0.05), respectively, in skeletal muscle of obese Zucker rats. In vivo insulin-induced tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 was depressed by 82% (p < 0.05) and 86% (p < 0.05), respectively. In the meantime, in vitro insulin-stimulated receptor tyrosine kinase activity in obese rats was decreased by 39% (p < 0.05). Dephosphorylation of the insulin receptor by prior alkaline phosphatase treatment increased insulin-stimulated receptor tyrosine kinase activity in both lean and obese Zucker rats, but the increase was three times greater in obese Zucker rats (p < 0.05). These findings suggest that excessive serine/threonine phosphorylation of the insulin receptor in obese Zucker rats may be a cause for insulin resistance in skeletal muscle.

Animals↗
PubMed1999

Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix contortrix, inhibits angiogenesis.

Contortrostatin, a 13.5 kDa disulfide-linked homodimeric polypeptide possessing an Arg-Gly-Asp sequence, was isolated from venom of the southern copperhead snake. Daily injection of contortrostatin into the primary tumor of human breast cancer MDA-MB-435 carried in nude mice significantly inhibited tumor growth and neovascularization of the tumor tissue. On the chick embryo chorioallantoic membrane, contortrostatin inhibited angiogenesis induced by MDA-MB-435 cells, basic fibroblast growth factor, and vascular endothelial growth factor. In addition, contortrostatin effectively blocked adhesion of human umbilical vein endothelial cells (HUVEC) to immobilized vitronectin and significantly inhibited invasion of HUVEC through a Matrigel barrier. Competitive binding assays and adhesion assays with different integrin antibodies suggested that integrin alpha(v)beta3 is a binding site for contortrostatin on vascular endothelial cells. Detachment of HUVEC from vitronectin by contortrostatin induced apoptosis. HUVEC adhered and spread well on immobilized contortrostatin without undergoing apoptosis, suggesting that it is the inhibition of adhesion and spreading of HUVEC on extracellular matrix proteins, rather than binding of contortrostatin to integrins per se, that triggers apoptosis. We conclude that contortrostatin binds to alpha(v)beta3, and interferes with the anchorage-dependent survival mechanism of the vascular endothelial cells, and the mobility of the cells. The consequent suppression of angiogenesis is an important component of the antineoplastic activity of contortrostatin.

Journal Article↗
PubMed1999

Easy detection of all T cell receptor gamma (TCRG) gene rearrangements by Southern blot analysis: recommendations for optimal results.

Southern blot analysis of T cell receptor (TCR) gene rearrangements has proven to be a helpful tool to establish clonality in T cell leukemias and lymphomas. To improve the detection of clonal TCR gamma (TCRG) gene rearrangements by Southern blot analysis, we designed four new Jgamma probes and determined the most optimal restriction enzymes to be used with these probes. Based on detailed analysis of the sequences as well as on hybridization experiments with the TCRGJ21 probe, the Jgamma1.2 and Jgamma2.1 downstream areas were found to be highly homologous, suggesting that during evolution the duplication of the Jgamma region was followed by deletion of the tentative Jgamma2.2 gene segment. Southern blot analysis of 51 T cell acute lymphoblastic leukemias (T-ALL) revealed that all TCRG gene rearrangements can be detected by use of the TCRGJ13 probe in EcoRI digests and the TCRGJ21 probe in PstI digests. Additional probes and digests allow a more precise identification of the exact type of TCRG gene rearrangements in the majority of cases. Almost 90% of the TCRG gene rearrangements in T-ALL involved the Jgamma2 region (16% Jgamma2.1 and 72% Jgamma2.3), whereas Jgamma1 region rearrangements were particularly found in TCRgammadelta+ T-ALL. This information has implications for design of primer sets for PCR analysis at diagnosis and for PCR target choice in detection of minimal residual disease during follow-up of T-ALL patients.

Blotting, Southern↗
PubMed1999

Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers.

AIMS: Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials in Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV). Therefore, the influence of the CYP2D6 genotypes on venlafaxine pharmacokinetics was examined in a Japanese population. METHODS: Twelve adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotypes were determined by codon 188C/T, 1934G/A, 2938G/A and 4268G/C mutations using endonuclease tests based on PCR and by Xba I-RFLP analysis. Subjects were categorized into the following 3 groups (n=4 in each group); Group1: CYP2D6*10/*10, *5/*10, Group2: CYP2D6*1/*10, *2/*10 and Group3: CYP2D6*1/*1, CYP2D6*1/*2. Venlafaxine (25 mg, n=6; 37.5 mg, n=6) was administered orally at 09.00 h following an overnight fast. Plasma concentrations of venlafaxine and ODV were monitored by h.p.l.c. for 48 h. RESULTS: The Cmax and AUC of venlafaxine were 184% and 484% higher in the group 1 subjects than in the group 3 subjects, and 101% and 203% higher in the group 1 than in the group 2, respectively. CONCLUSIONS: These results suggest that CYP2D6*10 influences the pharmacokinetics of venlafaxine in a Japanese population.

Adult↗
PubMed1999

Severity of nausea and vomiting during pregnancy: what does it predict?

BACKGROUND: Relationships between the severity of nausea and vomiting during pregnancy and selected demographic (employment status, parity, age, smoking) and pregnancy outcome (birthweight, gender) variables are described. METHODS: Women who volunteered for a community-based clinical trial were eligible for inclusion in this study. On three occasions, 12 hours apart, during early pregnancy using a continuous measure of nausea, vomiting, and retching, women assessed the amount, duration, and severity of symptoms as they occurred. After the birth of their infants, they provided information about the duration of nausea, vomiting, and retching as well pregnancy outcome information by responding to a mailed questionnaire. Multivariate methods were used to analyze data. RESULTS: More severe vomiting in early pregnancy was likely to continue for a longer period of time and was related to decreased infant birthweight. Gestational age, parity status, and severity of vomiting were predictors of infant birthweight and together explained 22 percent of the variance in birthweight. A significant relationship between fetal gender and severity of nausea and vomiting was not found. CONCLUSIONS: It may be possible to identify women at risk for third trimester vomiting and to provide appropriate nutritional support and counseling so that their risk of having a low-birthweight infant is reduced. A larger sample would be required to assess the relationship between fetal gender and severity of nausea, vomiting, and retching.

Adult↗
PubMed1999

Effect of trans fatty acids on calcium influx into human arterial endothelial cells.

BACKGROUND: A recent task force of The American Society for Clinical Nutrition and American Society for Nutritional Sciences recommended in a position paper on trans fatty acids that models be developed to assess the effects of changes in fat intake on disease risk. OBJECTIVE: The objective was to investigate, using human arterial endothelial cells as a model, the influence of trans fatty acids and magnesium on cell membrane composition and on calcium influx into arterial cells, a hallmark of atherosclerosis. DESIGN: Endothelial cells were cultured for 3 d in media with high (adequate) or low (inadequate) amounts of magnesium plus various concentrations of trans,trans linoelaidic; cis,cis linoleic; trans elaidic; oleic; or stearic acids. The cells were then harvested and the fatty acid composition and the amount of (45)Ca(2+) incorporated into the cell was determined. RESULTS: The percentage of fatty acids incorporated into the endothelial cells was proportional to the amount added to the culture medium. Adequate magnesium was crucial in preventing calcium influx into endothelial cells. Without an adequate amount of magnesium in the culture medium, linoelaidic and elaidic acids, even at low concentrations, increased the incorporation of (45)Ca(2+) into the cells, whereas stearic acid and oleic acid did not (P < 0.05). CONCLUSION: Our model indicated that a diet inadequate in magnesium combined with trans fat may increase the risk of calcification of endothelial cells.

Calcium↗
PubMed1999

Novel modulation of a nicotinic receptor channel mutant reveals that the open state is stabilized by ethanol.

Ethanol enhances the gating of a family of related ligand-gated ion channels including nicotinic acetylcholine, serotonin type 3, gamma-aminobutyric acid-A, and glycine receptors. This common action may reflect shared molecular and kinetic mechanisms. In all of these receptors, ethanol enhances multichannel currents elicited with low agonist concentrations, but not with high agonist concentrations. A single mutation in the nicotinic receptor beta subunit, betaT263I, causes ethanol to enhance multichannel currents elicited with both low and high acetylcholine concentrations. Based on the ratios of acetylcholine EC50s in the presence and absence of ethanol, this mutant's sensitivity to enhancement is similar to wild type. Ethanol enhancement of betaT263I receptor activation shows no voltage dependence. In the presence of ethanol, the apparent single-channel conductance of the betaT263I receptor is reduced and the apparent channel lifetime is lengthened. Both the 28% increase in maximal current and the 2-fold reduction in EC50 observed at 300 mM ethanol are quantitatively predicted by simulation of a simple kinetic scheme in which ethanol increases by 4-fold the ratio of microscopic opening rate (beta) to closing rate (alpha) for acetylcholine-bound betaT263I receptors. We conclude that ethanol enhancement of betaT263I currents reflects stabilization of its open-channel state relative to agonist-bound closed states. Ethanol effects in wild-type receptors can also be explained by this mechanism.

Acetylcholine↗
PubMed1999

Tat activates human immunodeficiency virus type 1 transcriptional elongation independent of TFIIH kinase.

Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of Cdk9 and cyclin T1, to the HIV-1 promoter via cooperative binding to the nascent HIV-1 transactivation response RNA element. The Cdk9 kinase activity has been shown to be essential for P-TEFb to hyperphosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II and mediate Tat transactivation. Recent reports have shown that Tat can also interact with the multisubunit transcription factor TFIIH complex and increase the phosphorylation of CTD by the Cdk-activating kinase (CAK) complex associated with the core TFIIH. These observations have led to the proposal that TFIIH and P-TEFb may act sequentially and in a concerted manner to promote phosphorylation of CTD and increase polymerase processivity. Here, we show that under conditions in which a specific and efficient interaction between Tat and P-TEFb is observed, only a weak interaction between Tat and TFIIH that is independent of critical amino acid residues in the Tat transactivation domain can be detected. Furthermore, immunodepletion of CAK under high-salt conditions, which allow CAK to be dissociated from core-TFIIH, has no effect on either basal HIV-1 transcription or Tat activation of polymerase elongation in vitro. Therefore, unlike the P-TEFb kinase activity that is essential for Tat activation of HIV-1 transcriptional elongation, the CAK kinase associated with TFIIH appears to be dispensable for Tat function.

Cyclin T↗
PubMed1999

Evaluation of induction of CYP3A mRNA using the HepG2 cell line and reverse transcription-PCR.

Cytochrome P-450 3A (CYP3A) is a drug-metabolizing enzyme dominant in the human liver. We have designed a useful method for evaluation of induction of CYP3A mRNA by various drugs using HepG2 cells known to retain liver-cellular functions. Using semi-quantitative reverse transcription-PCR (RT-PCR), we demonstrated that cultured HepG2 cells constitutively expressed CYP3A mRNA. This mRNA was expressed at high levels in culture for several days and was further induced by several drugs (e.g. rifampicin (RFP), dexamethasone). Treatment of HepG2 cells with RFP induced CYP3A mRNA in a dose- and time-dependent manner. Cells in culture for 48 h with 1 and 50 micromol/l RFP increased 2.7- and 5.0-fold in CYP3A mRNA expression in comparison with untreated controls, respectively. In contrast, no change in the amount of CYP3A mRNA was observed when the cells were treated with cimetidine which has been shown to inhibit CYP3A activity. Our method using a combination of HepG2 cells and RT-PCR allowed evaluation of the degree of induction of CYP3A mRNA both easily and rapidly.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Influence of low magnesium concentrations in the medium on the antioxidant system in cultured human arterial endothelial cells.

Using cultured human endothelial cells, we investigated the contribution of concentrations of magnesium to the antioxidant system and oxidative stress. Cells were cultured at decreasing magnesium levels (569, 380, 190 and 95 microM) for 72 h. We then measured the amount of released hydrogen peroxide (H2O2) from the cells, the consumption of exogenous H2O2, the intracellular reduced glutathione (GSH) and the oxidized glutathione (GSSG) contents and the activities of glutathione reductase and catalase. Magnesium at a level of 949 microM was used as a control. The effect of magnesium deficiency on cellular membrane permeability was determined by measurement of the amount of [14C] amino acid mixture released from the cells. The results showed that during 72 h of magnesium-deficient treatment, the H2O2 release from the cells gradually increased and consumption of exogenous H2O2 was enhanced during the first 48 h of treatment. GSH content gradually decreased but GSSG was not affected. The activity of glutathione reductase was first stimulated and then inhibited. Catalase activity was gradually reduced. [14C]Amino acid mixture release from the cells continuously increased. We suggest that magnesium deficiency affected the intracellular antioxidant system in cultured endothelial cells.

Amino Acids↗
PubMed1999

The accentuating effect of low magnesium concentration on cholestane-3 beta, 5 alpha, 6 beta-triol-induced decrease of LDL uptake by cultured endothelial cells.

The effects of cholestane-3 beta, 5 alpha, 6 beta-triol (TriolC) and/or low magnesium on uptake, internalization, surface binding and degradation of 125I-LDL were investigated in cultured endothelial cells. TriolC (at a level of 1 microgram/ml and higher) or magnesium (at a level of 188 microM and lower) in cultured medium decreased significantly the uptake, internalization, surface binding and degradation of 125I-LDL. When TriolC and low magnesium were combined, the significant inhibitions of uptake, internalization, surface binding and degradation of 125I-LDL were also observed although by themselves at these levels (TriolC lower than 1 microgram/ml and magnesium higher than 188 microM) they had no obvious effects. Our work suggests that a combination of low magnesium and TriolC have additive inhibitive effects on uptake, internalization, surface binding and degradation of 125I-LDL.

Cell Membrane↗
PubMed1999

Reversal effect of TTD on human multidrug resistant KBV200 cell line.

The reversal effect of TTD (a Chinese medicine) on human multidrug- resistant KBV200 cell line was studied and compared with verapamil (VPL). The chemosensitivity of KBV200 was detected by MTT assay in vitro and the level of MDR1 mRNA of KBV200 was investigated by RT-PCR. The cytotoxicity of TTD to KBV200 and the parent sensitive cell line KB is very low and nearly same with a concentration of 10(-6) mol x L(-1). With the concentration TTD increased VCR cytotoxicity on KBV200, 50% inhibitory concentration (IC50) decreased from 1122.5+/-72.36 mol x L(-1) to 31.76+/-5.4 nmol x L(-1) (p<0.001). It was more effective than VPL was (p<0.01). The combination of low concentration of TTD (10(-8) mol x L(-1)) and VCR (100 nmol x L(-1)) has significantly increased VCR cytotoxicity on KBV200, cell Surviving Fraction decreased from 0.91+/-0.056 to 0.74+/-0.07 (p<0.02). TTD did not inhibit the expression of MDR1 mRNA of KBV200 with the concentration of 10(-6) mol x L(-1). These data indicated that TTD could reverse VCR resistance of KBV200 and may be useful in enhancing the clinical effectiveness of VCR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

[Over-expression of a polyketide synthase (PKS) module of a giant polyene antibiotic gene cluster in E. coli by double induction].

A 2,671 bp DNA carrying a type I PKS module with KS and AT domains from Streptomyces sp. FR-008 was cloned in-frame into the BamHI site immediately downstream of the PT7 promoter of the E. coli expression vector pET-15b, no considerable expression under IPTG induction was detected. The same PKS gene cloned downstream of the tandem PRPL promoters of pBV220 also yielded no over-expression under 42 degrees C induction. This gene was, however, over-expressed when it was cloned downstream of the tandem PRPT7 or PRPLPT7 promoters. In the case of the tandem PRPLPT7 promoters, the over-expression was dependent on the 42 degrees C plus IPTG double induction. While in the case of the tandem PRPT7 promoters, over-expression could be achieved when the gene was induced by IPTG or 42 degrees C individually or by IPTG and 42 degrees C double induction. Based on these experiences an expression vector pHZ330 containing the tandem PRPT7 promoters was constructed. In addition, the PKS protein expressed in E. coli was injected into rabbits to generate PKS-specific antibodies. Western blotting experiment indicated that these antibodies were PKS-specific which could be used either for the study of the PKS gene cluster or for the detection of the heterologous expression of Streptomyces sp. FR-008 PKS genes.

Animals↗
PubMed1999

[Clinical significance of cardiac axis determination in prenatal echocardiographic diagnosis of fetal congenital heart disease].

OBJECTIVE: To investigate the clinical significance of cardiac axis determined by echocardiography in prenatal diagnosis of fetal congenital heart disease (CHD). METHODS: 518 high risk fetuses for CHD were and 90 normal fetuses were examined by echocardiography. Cardiac axis was measured on four-chamber view and fetal cardiac anatomical structure was examined in multiple views to determine CHD. RESULTS: The 35 fetuses with CHD diagnosed by prenatal echocardiography. There is significant difference of caidiac axis between CHD group (58.1 +/- 15.7 degree) and normal group (44.8 +/- 10.3 degree, P < 0.01). Sensitivity of CHD diagnosis using four-chamber view alone is 68.5%, it will be elevated to 91.4% by combination of four-chamber view and cardiac axis determination (P < 0.05). CONCLUSION: Cardiac axis play an important role in fetal echocardiographic screening for CHD and it should be measured routinely as part of the four-chamber view of the fetal heart. The normal range of fetal cardiac axis is 20 to 75 degree. If it was more than 75 degree, the CHD should be suspected.

Adult↗
PubMed1999

[In vitro reversal effect of cyclosporin A in combination with cytokines on multidrug resistant cell line K562/A02].

OBJECTIVE: To explore the reversal effect of cyclosporin A(CsA) in combination with cytokines on multidrug resistant cell line K562/A02. METHOD: The cytotoxicities of daunorubicin(DNR) were assayed by MTT method. Intracellular rhodamine(Rh123) concentration was measured by flow cytometry. P-glycoprotein(p-gp) expression was analyzed for staining with monoclonal JSB-1. Mdr1 mRNA expression was detected by RT-PCR. RESULTS: The cytotoxicities of DNR to K562/A02 were enhanced by 1 mumol/L CsA, 500 U/ml IFN-alpha and 200 U/ml, IL-2 respectively, and their IC50 was (3.78 +/- 0.03), (13.77 +/- 0.38) mu/ml, (18.5 +/- 0.60) micrograms/ml. Their reversal effect was 6.70, 1.84 and 1.37 times than that of K562/A02. But IC50 of combined CsA and IFN-alpha was (1.71 +/- 0.19) micrograms/ml; its reverse effect increased in 14.8 times. The combination could increase intracellular Rh123 accumulation significantly as compared with either of them alone, but p-gp and mdr1 mRNA expression were not decreased obviously. CsA in combination with IL-2 didn't show a synergistic effect. CONCLUSION: Mdr could be partially reversed by cytokines or low doses CsA(1 mumol/L), but the combination of CsA and IFN-alpha showed a greater synergistic reversal interaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Relationship between bone mineral density and polymorphism of the estrogen receptor gene in healthy postmenopausal women in China.

OBJECTIVE: To investigate the possible relationship between bone mineral density and polymorphism of the estrogen receptor (ER) gene in Shanghai healthy postmenopausal women. METHODS: 250 unrelated healthy postmenopausal women were selected for bone mineral density (BMD) determination by Dual energy X-ray absorptiometry (DEXA) and polymorphism of estrogen receptor gene analyses by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Pvu II polymorphisms of ER gene was associated with low Troch BMD (P = 0.0153) while there was no significant relationship between Xba I polymorphism of ER gene and BMD at any of skeletal sites included in the present study, and the combination of Pvu II and Xba I polymorphisms of ER gene was significantly associated with both low Lumbar 2-4 (P = 0.0369) and Troch (P = 0.0384) BMD. Multiple stepwise regression analysis also indicated that two combined polymorphisms were correlated significantly with Lumbar 2-4 BMD (P = 0.0254) while this correlation was not revealed at any other skeletal sites. CONCLUSION: There is significant relationship between the polymorphism of ER gene and both Lumbar 2-4 BMD and Troch BMD. It is significant to explore the pathogenesis of osteoporosis and to prevent the development of osteoprosis by use of molecular genetics.

Absorptiometry, Photon↗