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Biomedical subjects

G Cao

Publications and source records attributed to G Cao.

At least 109 records · Page 6Linked to original sources
PubMed1998

Comparison of different analytical methods for assessing total antioxidant capacity of human serum.

Three assays were compared for the determination of total antioxidant capacity in human serum: the oxygen radical absorbance capacity (ORAC) assay, the Randox Trolox-equivalent antioxidant capacity (Randox-TEAC) assay, and the ferric reducing ability (FRAP) assay. There was a weak but significant linear correlation between serum ORAC and serum FRAP. There was no correlation either between serum ORAC and serum TEAC or between serum FRAP and serum TEAC. The effect of dilution on the serum TEAC value and the use of inhibition percentage at a fixed time, without considering the length of inhibition time in the quantitation of results, adversely affected the Randox-TEAC assay. The FRAP assay is simple and inexpensive but does not measure the SH-group-containing antioxidants. The ORAC assay has high specificity and responds to numerous antioxidants. By utilizing different extraction techniques in the ORAC assay, one can remove serum proteins and also make some gross differentiation between aqueous and lipid-soluble antioxidants. However, the ORAC assay requires approximately 60 min more than the FRAP or Randox-TEAC assay to quantitate results.

Aged↗
PubMed1997

Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor 1.

The scavenger receptor, class B, type 1 receptor (SR-BI) mediates the selective transport of lipids from high density lipoprotein to cells. We describe the structure and subchromosomal location of human SR-BI and provide evidence that it is regulated by the transcription factor, steroidogenic factor 1 (SF-1). SR-BI resides on chromosome 12q24.2-qter, spans approximately 75 kilobase pairs, and contains 13 exons. RNA blot analysis of human tissues reveals an expression pattern similar to that described previously for rodents with the highest levels of mRNA in the adrenal gland, ovary, and liver. Unlike rodents, human SR-BI was expressed at high levels in the placenta. The transcription start site for SR-BI was mapped, and DNA sequence analysis revealed a binding site for SF-1 in the proximal 5'-flanking sequence. SF-1, an orphan member of the nuclear hormone receptor gene family, plays a key role in the regulation of steroidogenesis and is expressed at high levels in steroidogenic tissues. SF-1 binds to the SR-BI promoter in a sequence-specific manner, and efficient transcription from this promoter in adrenocortical Y1 cells is dependent on an intact SF-1 site. These data extend our understanding of SF-1 function within steroidogenic tissues and suggest that SR-BI, which serves to supply selected tissues with lipoprotein-derived lipids, is part of the repertoire of SF-1-responsive genes involved in steroidogenesis.

Base Sequence↗
PubMed1997

Mortality from coronary heart disease and cardiovascular disease among adult U.S. Hispanics: findings from the National Health Interview Survey (1986 to 1994).

OBJECTIVES: We sought to estimate the coronary heart disease (CHD) and cardiovascular disease (CVD) mortality experience of U.S. Hispanics. BACKGROUND: Limited information is available concerning the mortality from CHD among U.S. Hispanics, the nation's second largest minority group. METHODS: The study used data from the National Health Interview Survey (1986 to 1994), including representative national samples of 246,239 non-Hispanic whites, 38,042 blacks and 14,965 Hispanics who were > or = 45 years old at baseline. Mean follow-up of mortality was 5 years (range 1 to 10). RESULTS: During the follow-up period, 27,702 whites (11%), 4,976 blacks (13%) and 1,061 Hispanics (7%) died. Among men, the age-adjusted total mortality per 100,000 person-years was 3,089 in whites and 2,466 in Hispanics, and among women, it was 1,897 and 1,581 in whites and Hispanics, respectively. The Hispanic/white mortality rate ratio for CHD was 0.77 (95% confidence interval [CI] 0.64 to 0.93) and 0.82 (95% CI 0.66 to 1.01) for men and women, respectively. The rate ratio was 0.79 (95% CI 0.68 to 0.91) and 0.80 (95% CI 0.69 to 0.94), respectively, for mortality from cardiovascular diseases. Given the lower all-cause mortality in Hispanics, the proportion of total deaths due to CHD and CVD was similar between the two populations for the same gender and were, respectively, 29.7% and 44.7% in white men, 28.1% and 44.3% in Hispanic men, 24.9% and 43.2% in white women and 24.1% and 41% in Hispanic women. CONCLUSIONS: These data from a cohort of a large national sample are consistent with vital statistics that show that all-cause, CHD and CVD mortality is approximately 20% lower among adult Hispanics than among whites in the United States.

Aged↗
PubMed1997

Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2).

Sterol-regulatory element binding protein (SREBP) 1 and SREBP2 are ubiquitously expressed transcription factors that play key roles in the regulation of cholesterol and fatty acid metabolism. SREBP1 and SREBP2 share approximately 47% sequence identity and map to chromosomes 17 and 22, respectively. The gene encoding SREBP1 (SREBF1) has been cloned and characterized. In this paper we describe the gene structure and 5'-flanking sequence of SREBF2. SREBF2 spans 72 kb and is composed of 19 exons and 18 introns. The locations of the exon/intron boundaries of SREBF2 are remarkably similar to those of SREBF1, but SREBF2 is approximately 2.8 times larger in size. The 5'-flanking regions of SREBF2 and of two alternatively spliced forms of SREBF1, SREBF1a and SREBF1c, were sequenced, and the SREBF2 transcription start site was determined. A perfect 10-bp sterol regulatory element (SRE)-1 sequence was present in the promoter region of SREBF2. No SRE-1 was identified in the 5'-flanking sequences of either SREBF1a or SREBF1c, but several E-box sequences were present in SREBP1c. Thus, analysis of the 5'-flanking regions provides support that these two transcription factors, though similar in their coding sequence and overall gene structure, have different physiological roles. Finally, evidence is presented for the presence of another expressed gene of unknown function located 500 bp upstream of SREBF2.

Amino Acid Sequence↗
PubMed1997

Stress proteins are not induced in mammalian cells exposed to radiofrequency or microwave radiation.

The induction of stress proteins in HeLa and CHO cells was investigated following a 2 h exposure to radiofrequency (RF) or microwave radiation. Cells were exposed or sham exposed in vitro under isothermal (37 +/- 0.2 degrees C) conditions. HeLa cells were exposed to 27- or 2450 MHz continuous wave (CW) radiation at a specific absorption rate (SAR) of 25 W/kg. CHO cells were exposed to CW 27 MHz radiation at a SAR of 100 W/kg. Parallel positive control studies included 2 h exposure of HeLa or CHO cells to 40 degrees C or to 45 microM cadmium sulfate. Stress protein induction was assayed 24 h after treatment by electrophoresis of whole-cell extracted protein labeled with [35S]-methionine. Both cell types exhibited well-characterized responses to the positive control stresses. Under these exposure conditions, neither microwave nor RF radiation had a detectable effect on stress protein induction as determined by either comparison of RF-exposed cells with sham-exposed cells or comparison with heat-stressed or Cd++ positive control cells.

Animals↗
PubMed1997

The effect of erythromycin on the CYP3A component of sertindole clearance in healthy volunteers.

The effect of erythromycin on the pharmacokinetic disposition of oral sertindole, a new antipsychotic compound, was investigated. Ten subjects who completed the study received a single 4-mg dose of sertindole without or with concomitant erythromycin 250 mg taken orally 4 times daily. Coadministration of sertindole and erythromycin led to a 33% decrease (P < 0.05) in mean (+/- SD) time to reach maximum plasma concentration (tmax) value and a 15% elevation (P < 0.05) in the mean maximum plasma concentration (Cmax) value of sertindole. The mean area under the concentration-time curve (AUC) value of sertindole did not change significantly in the presence of erythromycin (alone: 159 +/- 111 ng.hr/mL, in combination: 179 +/- 144 ng.hr/mL, P > 0.05). The presence of erythromycin also significantly increased the dehydrosertindole Cmax and AUC means by 16% and 21%, respectively, possibly due to inhibition of the CYP3A metabolic isozyme responsible for the elimination of this metabolite. The rate of absorption of sertindole and the rate of appearance of dehydrosertindole in the systemic circulation after a 4-mg sertindole single dose were slightly enhanced by concomitant dosing of erythromycin. In conclusion, there is a small but noticeable effect of erythromycin on the pharmacokinetic disposition of sertindole. The effects are believed to have little clinical significance.

Administration, Oral↗
PubMed1997

The pharmacokinetic and pharmacodynamic interaction between zileuton and terfenadine.

OBJECTIVES: The effects of zileuton on terfenadine pharmacokinetics, and the effects of terfenadine alone and the combination on the duration of the QTc interval and the morphology of the TU complex were examined. METHODS: The study was double-blind, randomized, placebo-controlled, two period cross-over in 16 healthy volunteers. During each period, subjects received 60 mg of terfenadine every 12 h on days 1 to 7 and 600 mg of either zileuton or placebo for zileuton every 6 h on days 1 to 10. Blood samples were obtained on days 7 to 10 and serial ECGs were performed on days -1 and 7 in both periods. RESULTS: The combination of zileuton and terfenadine was well tolerated. Coadministration of zileuton with terfenadine resulted in a significant increase in the mean AUC and Cmax of terfenadine by approximately 35% and the mean AUC and Cmax of carboxyterfenadine by approximately 15%. The maximum concentration of terfenadine observed in the study was 9.6 ng.ml-1. The addition of zileuton to terfenadine did not result in significant changes in the evaluated ECG-recordings (QTc interval and morphology of TU complex). The difference in means for both maximum and average QTc interval was very small (< or = 2.3 ms), and there were no clinically significant changes in individual values. CONCLUSIONS: The relatively small pharmacokinetic effect of zileuton on terfenadine metabolism, with no change in the QTc interval, is unlikely to be of clinical significance. The interaction is minimal in comparison to the background variability of the population.

Adult↗
PubMed1997

Pharmacokinetics of sertindole in healthy young and elderly male and female subjects.

OBJECTIVE: The pharmacokinetic disposition of oral sertindole, a new selective antipsychotic compound, in young and elderly male and female subjects was investigated. STUDY DESIGN: A total of 46 subjects (12 young males, 11 elderly males, 11 young females, and 12 elderly females) received 4 mg/day sertindole (once a day; days 1 through 3) for 3 consecutive days, 8 mg/day sertindole for 3 consecutive days (days 4 through 6), and 12 mg/day sertindole for 10 consecutive days (days 7 through 16). RESULTS: Age and gender did not appear to have any effect on the plasma binding of sertindole, despite a lower albumin concentration in elderly subjects. After multiple dosing of 12 mg sertindole, the mean peak plasma concentration (Cmax) values for young and elderly female subjects were 20% and 31% higher than those observed for male subjects of comparable age (p < 0.05). The mean values for area under the plasma concentration-time curve [AUC(0-24)] of female subjects were 29% higher than those observed in male subjects of similar age (p < 0.05). There were no statistically significant age-related differences in Cmax and AUC(0-24) (or apparent total plasma clearance), and there were no gender- or age-related differences for the elimination rate constant or values for apparent volume of distribution during the terminal elimination phase after the last 12 mg dose on day 16 (p > 0.05). CONCLUSIONS: There are no differences between young and elderly subjects in the absorption and elimination of sertindole. The higher Cmax and AUC values in females may be a result of a higher extent of absorption or a dependence of sertindole clearance on lean body mass.

Absorption↗
PubMed1997

Population analysis of the pharmacokinetics and pharmacodynamics of seratrodast in patients with mild to moderate asthma.

BACKGROUND: Seratrodast, a potent thromboxane receptor antagonist, is approved in Japan for the treatment of asthma and currently is being developed in the United States. METHODS: This was a phase II, randomized, double-blind, parallel-group, placebo-controlled 15-center study of seratrodast in patients with mild to moderate asthma. A total of 183 patients were randomly assigned to receive daily doses of either placebo, or 80 mg seratrodast, or 120 mg seratrodast for 8 weeks. Pharmacokinetic and pharmacodynamic modeling was carried out by means of the population approach. A two-compartment model with zero-order input and first-order elimination best fitted the plasma concentration-time data. RESULTS AND CONCLUSIONS: The pharmacokinetics of seratrodast were linear after single and multiple dosing for 8 weeks. The population estimates for oral clearance and apparent volume of distribution were 8.5 ml/hr/kg and 43.3 ml/kg, respectively. All pharmacokinetic parameters (the oral central compartment clearance, the volumes of distribution of the central and peripheral compartments, and the intercompartmental clearance) were estimated with a precision of 10% or less and were found to be associated with body weight. The residual variability was 30%. The values of oral clearance estimated in this study in male patients were similar to those previously estimated in healthy male subjects. Seratrodast at a dose of 120 mg daily produced an increase in forced expiratory volume in 1 second (FEV1) from baseline that was linearly correlated with its plasma concentrations. The average slope of the concentration-effect relationship was 0.222% and 0.470% per microgram/ml after single and multiple dosing, respectively. Interpatient variability in response was mainly affected by the initial severity of the disease. A lower percentage of predicted FEV1 (i.e., more severe obstruction) was associated with higher slopes, and greater increases in FEV1.

Adult↗
PubMed1997

Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships.

The antioxidant and prooxidant behavior of flavonoids and the related activity-structure relationships were investigated in this study using the oxygen radical absorbance capacity assay. Three different reactive species were used in the assay: 2,2'-azobis(2-amidino-propane) dihydrochloride, a peroxyl radical generator; Cu(2+)-H2O2, mainly a hydroxyl radical generator; and Cu2+, a transition metal. Flavonoids including flavones, isoflavones, and flavanones acted as antioxidants against peroxyl and hydroxyl radicals and served as prooxidants in the presence of Cu2+. Both the antioxidant and the copper-initiated prooxidant activities of a flavonoid depend upon the number of hydroxyl substitutions in its backbone structure, which has neither antioxidant nor prooxidant action. In general, the more hydroxyl substitutions, the stronger the antioxidant and prooxidant activities. The flavonoids that contain multiple hydroxyl substitutions showed antiperoxyl radical activities several times stronger than Trolox, an alpha-to copherol analogue. The single hydroxyl substitution at position 5 provides no activity, whereas the di-OH substitution at 3' and 4' is particularly important to the peroxyl radical absorbing activity of a flavonoid. The conjugation between rings A and B does not affect the antioxidant activity but is very important for the copper-initiated prooxidant action of a flavonoid. The O-methylation of the hydroxyl substitutions inactivates both the antioxidant and the prooxidant activities of the flavonoids.

Antioxidants↗
PubMed1997

Complete regression of established murine hepatocellular carcinoma by in vivo tumor necrosis factor alpha gene transfer.

BACKGROUND & AIMS: Although tumor necrosis factor (TNF)-alpha possesses a potent antitumor activity, systemic administration of TNF-alpha causes severe side effects. To circumvent this, the efficacy of tumor cell-targeted TNF-alpha gene therapy was investigated. METHODS: Murine hepatocellular carcinoma (HCC) cells were infected with MNSM-Alb e/p-TNF-alpha retroviruses carrying the murine TNF-alpha gene under the transcriptional control of the murine albumin gene promoter, and antitumor effects induced by TNF-alpha gene transfer were examined in vitro and in vivo. RESULTS: Although MNSM-Alb e/p-TNF-alpha retrovirally infected HCC cells showed the same in vitro cell growth as parental HCC cells, they lost their tumorigenicity when implanted in syngeneic mice and induced tumor immunity against parental HCCs. The retrovirally infected HCC cells also significantly inhibited the tumorigenicity of previously implanted parental HCCs. Furthermore, intratumoral administration of MNSM-Alb e/p-TNF-alpha retroviruses showed the antitumor effect against established HCCs, resulting in significantly prolonged survival periods. Most importantly, intratumoral implantation of MNSM-Alb e/p-TNF-alpha retroviral-producing cells completely abrogated established HCCs in mice. CONCLUSIONS: These results indicate the potential efficacy of transferring the TNF-alpha gene via retroviral vectors directly into tumors for gene therapy against HCCs.

Animals↗
PubMed1997

Exercise-induced oxidative stress before and after vitamin C supplementation.

Vitamin C (ascorbic acid) was supplemented (1 g/day) for 1 day and 2 weeks in the same subjects. Plasma thiobarbituric acid reacting substances (TBARS) and oxygen radical absorbance capacity (ORAC) before and after 30 min submaximal exercise were measured. Different vitamin C supplementations did not affect resting TBARS or ORAC. Following 30 min exercise, values for TBARS were 12.6 and 33% above rest with 1 day and 2 weeks of vitamin C supplementation, respectively, compared to 46% higher with placebo. ORAC did not significantly change (11%) after exercise with a placebo, nor when subjects were given vitamin C supplements for 1 day or 2 days (4.9% and 5.73%, respectively). TBARS:ORAC, a ratio representing oxidative stress, increased 32% (p < .05) with placebo compared to 5.8 and 25.8% with vitamin C supplements for 1 day and 2 weeks, respectively. It was concluded that exercise-induced oxidative stress was highest when subjects did not supplement with vitamin C compared to either 1 day or 2 weeks of vitamin C supplementation.

Adult↗
PubMed1997

[Effects of cytokines on somatostatin in nude mice bearing human renal cell carcinoma].

We studied the relationship between the production of SS and treatment with cytokines and a new method for the treatment of renal cell carcinoma. 4.4 x 10(6)RCC94616 cells were injected subcutaneously into the back of nude mice. Five groups with TNF, IL-2, rIFN, TNF + IL-2, TNF + rIFN and controls were randomly divided according to the mean diameter of experimental tumor. After the last injection of cytokines, 0.5-0.8 ml blood, 1g tumor tissue, para-tissue and normal tissue were havested respectively. Contents of SS were tested by radioimmunoassay. In the treatment groups with cytokines, the concentration of SS was changed, siginificantly increased in the TNF + IL-2 group (P < 0.01). The effect on distribution of SS by cytokines may also be mediated by the regulation of human immunity and antitumor activity. It may be suggested that the method of TNF + IL-2 + SS is best to treat renal cell carcinoma.

Adenocarcinoma, Clear Cell↗
PubMed1997

[ICAM-1 mRNA expression in the bronchial tissue of asthmatic guinea pigs].

To determine the expression of ICAM-1 mRNA in the bronchial tissue of asthmatic guinea pigs. The guinea pigs were divided randomly in to asthma, asthma treated with dexamethasone (DEX), and control groups. ICAM-1 expression was analyzed by in situ hybridization and the cellular infiltrate was evaluated by HE staining. In situ hybridization demonstrated ICAM-1 mRNA was mainly expressed in the cytoplasm of epithelial cells and endothelial cells. Compared with the control and DEX groups, a significant increase of ICAM-1 mRNA expression was observed in the bronchial tissue (P < 0.02 and 0.05 respectively). In asthmatic guinea-pigs, the intensity of ICAM-1 mRNA expression in bronchial tissue was correlated with total leucocyte infiltrate (P < 0.05). ICAM-1 expression in bronchial tissue may be related with the leucocyte infiltration and glucocorticoid may inhibit the expression of cell adhesion molecules.

Animals↗
PubMed1997

Evaluation of the effect of fluconazole on the pharmacokinetics of ritonavir.

The effects of fluconazole on the pharmacokinetics of the HIV protease inhibitor ritonavir were investigated after multiple dosing in an open-label study. In this randomized, two-period crossover study, eight healthy subjects received ritonavir alone (200 mg every 6 hr for 4 days) and ritonavir with fluconazole (400 mg on day 1, 200 mg every day on days 2-5) with a 2-week washout period. Ritonavir plasma concentrations were measured during the final four ritonavir dosing intervals (24 hr) and a 12-hr washout period. There were statistically significant increases in ritonavir C(max) and AUC0-24 (p < 0.02), with concurrent administration of fluconazole compared with administration of ritonavir alone. The difference between regimens in C(min) was marginally statistically significant (p = 0.089), and t(max) and beta were not statistically significantly different. Although some ritonavir parameters were affected by fluconazole, mean increases in C(max) and AUC were < or = 15% for the 24-hr period, and only 7-19% for individual dose intervals. Thus, the pharmacokinetics of ritonavir may be influenced only to a small extent when administered with fluconazole. These changes are probably of limited clinical significance and do not necessitate dosage adjustment of ritonavir when fluconazole is added to the regimen.

Adult↗
PubMed1996

Complementation of mutation in acyl-CoA:cholesterol acyltransferase (ACAT) fails to restore sterol regulation in ACAT-defective sterol-resistant hamster cells.

A previously described mutant line of Chinese hamster ovary cells, designated SRD-4, fails to synthesize cholesteryl esters, owing to a deficiency in the activity of acyl-CoA:cholesterol acyltransferase (ACAT). These cells also fail to suppress low density lipoprotein receptors or cholesterol synthesizing enzymes in the presence of 25-hydroxycholesterol. In the current studies we show that SRD-4 cells have three defects: 1) a point mutation in one allele at the ACAT locus that changes codon 265 from Ser to Leu, resulting in an inactive enzyme; 2) a silent allele at the other ACAT locus that does not produce detectable mRNA; and 3) a mutation, as yet undefined, that abolishes the ability of 25-hydroxycholesterol to inhibit the cleavage of both sterol regulatory element binding proteins (SREBP-1 and SREBP-2). Correction of the ACAT deficiency by transfection of a wild-type cDNA failed to restore inhibition of SREBP cleavage by 25-hydroxycholesterol, indicating that the ACAT deficiency and the sterol regulatory defect are caused by independent mutations. These data provide further insight into the interplay between ACAT activation and inhibition of SREBP cleavage by 25-hydroxycholesterol, and they indicate that these two processes can be disrupted independently by mutation.

Amino Acid Sequence↗