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Biomedical subjects

X P Xu

Publications and source records attributed to X P Xu.

At least 19 recordsLinked to original sources
PubMed1996

Restenosis is associated with decreased coronary artery nitric oxide synthase.

The purpose of the present study was to test the hypothesis that restenosis is associated with decreased constitutive nitric oxide synthase activity. Male miniswine with moderately elevated serum cholesterol levels underwent cardiac catheterization and oversized balloon injury to the right and left circumflex coronary arteries, followed 2 weeks later by repeat injury on the same coronary segments. After 4 weeks, the coronary arteries were either immediately frozen in liquid nitrogen or pressure-perfusion fixed and prepared for histologic examination. Constitutive nitric oxide synthase activity was quantified using a fibroblast reporter cell method, while constitutive nitric oxide synthase protein was compared between balloon-injured and non-balloon-injured arteries using Western blot analysis. Immunohistochemical studies were performed using a specific antibody against constitutive nitric oxide synthase protein. Following balloon injury, there was decreased constitutive nitric oxide synthase activity in balloon-injured coronary arteries, compared to distal non-balloon-injured segments from the same artery. Histological examination demonstrated an intact endothelium. Specific antibody staining revealed that there was less constitutive nitric oxide synthase protein reactivity by immunohistochemical analysis. Western analysis confirmed less constitutive nitric oxide synthase protein. The data are consistent with the hypothesis that restenosis is associated with decreased endothelial cell nitric oxide production. The data suggest this is secondary to a decreased amount of constitutive nitric oxide synthase enzyme in the endothelium. A deficiency in constitutive nitric oxide synthase enzyme may contribute to the impaired second messenger and paracrine functions of the endothelium observed during restenosis following balloon injury, including abnormal vasomotion, extracellular matrix formation, and platelet aggregation.

Angioplasty, Balloon, Coronary↗
PubMed1996

Differences in nitric oxide production in porcine resistance arteries and epicardial conduit coronary arteries.

The purpose of this study was to test the hypothesis that endothelial cells from resistance arteries and epicardial conduit coronary arteries differ in their expression of nitric oxide synthase (NOS) and calcium metabolism, and that these differences contribute to the mechanism underlying disparate physiological vasodilator responses observed between the two populations of vessels. The functional vasodilator responses of isolated resistance arteries and epicardial conduit coronary arteries were compared in vitro using both the receptor-independent agonist A23187 ionophore to increase intracellular calcium and the receptor-dependent agonist bradykinin. Constitutive NOS (cNOS) activity in monocultures of endothelial cells derived from resistance arteries and conduit arteries was assayed using a fibroblast-reporter cell method. Intracellular calcium concentration was assessed using fura-2 microfluorometry. Nitric oxide production was determined using a chemiluminescence technique, while cNOS protein was quantitated by Western blot analysis. A23187 was a less potent vasodilator of resistance arteries studied in vitro, compared to epicardial conduit arteries (EC50 = 1.6 microM, resistance artery vs. EC50 = 0.03 microM, conduit artery); however, bradykinin was more potent in resistance arteries (EC50 = 0.3 nM, resistance artery vs. EC50 = 2 nM, conduit artery). In pure monocultures of endothelium, nitric oxide production measured by chemiluminescence both basally and in response to A23187 was significantly less in resistance arteries (6.1 +/- 0.5, basal vs. 10.80 +/- 0.55, stimulated nmol/microgram protein), compared to conduit arteries (7.7 +/- 0.5, basal vs. 17.00 +/- 1.52, stimulated nmol/microgram protein; P < 0.05 resistance artery endothelium vs. conduit artery endothelium). cNOS enzyme activity assessed by cGMP production in reporter cell fibroblasts was also lower in resistance arteries compared to conduit arteries (0.17 +/- 0.03 vs. 0.33 +/- 0.05 fmol cGMP/microgram protein, respectively; P < 0.05 resistance artery endothelium vs. conduit artery endothelium). Conduit arteries expressed 2.1 x more cNOS protein than resistance arteries, as assessed by Western blotting of cellular homogenates. No significant differences were found with microfluorimetry in either basal or ionophore-stimulated intracellular calcium concentrations. The results signified that porcine resistance arteries expressed less NOS and produced less nitric oxide than epicardial conduit arteries both basally and in response to an increase in intracellular calcium. This difference was reflected functionally as a decreased vasodilatory response to increased intracellular calcium in resistance arteries that could not be explained on the basis of differences in the metabolism of intracellular calcium. In contrast, the functional vasodilator response of intact vessels to a receptor-mediated agonist was enhanced in resistance arteries compared to conduit arteries, suggesting an important role of signal transduction mechanisms in specific physiological responses. Thus, the ability of the endothelium to regulate on a regional basis the expression of NOS and integrate receptor-mediated responses with these differences may provide a mechanism for diverse vasomotor responses in different populations of vessels.

Animals↗
PubMed1996

Airway reactivity in welders: a controlled prospective cohort study.

In a 3-year survey, respiratory symptoms, spirometry, and methacholine reactivity were measured annually in welders (n = 51) and non-welder controls subjects (n = 54) to determine whether welding-related symptoms are associated with accelerated decline in lung function or changes in airway reactivity. In the cross-workshift study, maximal midexpiratory flow rate declined reversibly during a welding day, whereas 1-second forced expiratory volume and forced-vital capacity were unchanged. In the longitudinal study, the welders had significantly more reversible work-related symptoms of cough, phlegm, wheeze, and chest tightness than the non-welder shipyard control subjects. In this group of actively working welders, across-workshift changes in midflow and reversible symptoms were related to the welding occupation, but evidence for chronic irreversible effects on spirometry or airway reactivity was not seen over the 3 years of observation. The short period of observation was not optimal for detecting a chronic effect on lung function. Work practices and engineering controls may be successfully preventing irreversible respiratory effects, but not mild reversible effects, in this group of welders.

Adult↗
PubMed1996

[Association of air pollution with unscheduled outpatient visits in Beijing Longfu Hospital, 1991].

Outpatient visits to Beijing Longfu Hospital, a community-based hospital, were analyzed to assess the association of air pollution with daily outpatient visits in 1991. Measurements of total suspended particulate (TSP) were available for 224 days (mean was 359 micrograms/m3) and sulfur dioxide (SO2) for 221 days (mean was 124 micrograms/m3). The effects of TSP and SO2 were assessed by linear regressions adjusting for temperature, humidity, seasons and the workdays as covariables with a Markov correction for auto-correlation in time series data. There was a significant exposure-response relationship between TSP level and non-surgery outpatient visits but not for surgery visits. SO2 was only significantly associated with pediatric visits.

Air Pollutants↗
PubMed1995

Prostaglandin-mediated inhibition of nitric oxide production by bovine aortic endothelium during hypoxia.

OBJECTIVE: The present study utilized a monoculture of vascular endothelium to: (1) determine if nitric oxide (NO) production was decreased during hypoxia, (2) ascertain if specific prostaglandins were released in response to hypoxia, and (3) determine if cyclo-oxygenase inhibition would modulate hypoxia-induced decreases in NO production. METHODS: Bovine aortic endothelial cells (BAE cells) were grown to confluence on microcarrier beads. NO released in response to the receptor-independent agonist, A23187 calcium ionophore, was directly and continuously measured using a sensitive and specific chemiluminescence method. Cells were exposed to either "hypoxia" (pO2 = 10 mmHg) or "normoxia" (pO2 = 160 mmHg) for 30 min. NO was quantitatively measured with and without indomethacin (1.7 microM) in the incubation medium, and also following incubation with the prostacyclin analog, iloprost. The prostaglandins PGI2 and PGE2 released in response to hypoxia were quantitated using an enzyme immunoassay. RESULTS: Hypoxia significantly decreased NO production, resulting in a 22.8(2.1)% reduction in NO from 94.3(5.3) nmol/micrograms protein (during normoxia) to 73.5(2) nmol/micrograms protein (during hypoxia). Hypoxia significantly stimulated the production of PGI2 and PGE2, in excess of that released in response to A23187 when compared with normoxia. Following cyclo-oxygenase inhibition, the hypoxia-induced decrease in NO production was abolished (0.13 [2.7] % change relative to controls). Furthermore, iloprost (10 nM) directly inhibited NO production. CONCLUSIONS: The results demonstrate that ionophore-stimulated NO production is sensitive to oxygen tension, decreasing in response to hypoxia. Inhibition of prostaglandin synthesis restores NO production during hypoxia, while iloprost directly suppresses NO production. Thus, endothelium-derived prostanoids produced in response to hypoxia may modulate NO production via an autocrine negative feedback mechanism.

Animals↗
PubMed1995

Hypoxia activates nitric oxide synthase and stimulates nitric oxide production in porcine coronary resistance arteriolar endothelial cells.

OBJECTIVE: Hypoxia significantly alters vascular tone in coronary resistance arterioles during prolonged ischemia, potentially through the modulation of endothelial cell metabolism as well as endothelial function. The objective of this study was to test the hypothesis that constitutive nitric oxide synthase (cNOS) is sensitive to oxygen tension and that hypoxia increases the activity of cNOS and nitric oxide production in the porcine coronary microcirculation. METHODS: Monocultures of porcine coronary resistance arteriolar endothelial cells (RAEC) were isolated and proven to be endothelium based upon morphology, binding of acetylated LDL, and factor VIII antigen positivity. Cells were exposed to either hypoxia (pO2 = 10 mmHg) or normoxia (pO2 = 160 mmHg) for varying periods of time. Nitric oxide production was directly measured using a chemiluminescence method, while cNOS enzyme activity was assayed using a fibroblast-report cell method. cNOS protein was quantitated by Western blot analysis using the H32 monoclonal antibody to the endothelial cell constitutive isoform of NOS. RESULTS: Hypoxia significantly augmented A23187-stimulated nitric oxide production [23.77 (1.73) vs 14.94 (0.66) nmol . micrograms-1 protein, hypoxia vs. normoxia respectively, n = 8, P < 0.01]. Using the fibroblast reporter cell assay, cNOS activity was increased in RAEC after exposure to hypoxia for 30, 120 and 240 min [normoxia control: 0.16 (0.04) fmol . microgram-1 protein; hypoxia: 30 min = 1.00 (0.19), 120 min = 1.08 (0.04), 240 min = 1.26 (0.07) fmol . micrograms-1 protein (n = 6, p < 0.01)]. Western blots showed a single band at 135 kDa that was increased in homogenates of cells previously exposed to hypoxia. CONCLUSIONS: These experiments demonstrated that the regulation of cNOS is sensitive to oxygen tension. Hypoxia significantly activated constitutive nitric oxide synthase in coronary resistance arteriolar endothelial cells, and this was translated to an increased production of nitric oxide.

Animals↗
PubMed1994

Effects of smoking and drinking habits on urinary o-cresol excretion after occupational exposure to toluene vapor among Chinese workers.

The relationship between the time-weighted average intensity of exposure to toluene and o-cresol concentration in shift-end urine was investigated in nearly 500 factory workers of both sexes in China, together with a similar number of nonexposed control subjects. Toluene concentration (25 ppm as geometric mean and 550 ppm as the maximum) was monitored by diffusive sampling using carbon cloth as adsorbent followed by gas chromatographic (GC) analysis. o-Cresol (up to 7 mg/l) was measured by GC after acid hydrolysis of samples. Urinary o-cresol levels correlated significantly (r = 0.69-0.77; p < 0.01) with toluene exposure in men, women and the two sexes in combination, regardless of correction for urine density. When compared with hippuric acid, however, o-cresol was less sensitive as an indicator of exposure to toluene and is not a suitable biological marker for detecting low level toluene exposure. Since urinary o-cresol level was significantly reduced by smoking, drinking, and the two habits combined, it cannot be considered reliable as an indicator of exposure to toluene.

Air Pollutants, Occupational↗
PubMed1994

Women's respiratory health in the cotton textile industry: an analysis of respiratory symptoms in 973 non-smoking female workers.

As part of a 1992 survey of both environmental and occupational determinants of health, 973 non-smoking women aged 20-40 years who were employed in three comparable modern Chinese cotton textile mills were given a questionnaire that included questions on standard respiratory history and symptoms. All women had some potential exposure to cotton dust; mean employment was 8.7 years. Comparisons were made between those with lowest or no current exposure (job classification in administration, quality control, and testing, n = 112) and those in the more heavily exposed classifications (yarn production areas, n = 861). Association of symptoms with job was tested by logistic regression, adjusting for age, passive smoking at home, and the use of home coal burning stoves. Odds ratios for prevalence of current frequent symptoms in those working in production jobs, after adjustment for home exposure to passive tobacco smoke and coal heating, were frequent cough 2.23 (95% confidence interval (95% CI) 1.05-4.75), frequent phlegm 3.24 (1.54-6.84), shortness of breath 4.54 (1.40-14.72), and wheeze 2.96 (1.16-7.55). Nine cases with grade I byssinosis (chest tightness or shortness of breath on return to work after two days off) were found; all were in production jobs. In these non-smoking women textile workers, chronic respiratory symptoms were associated with job category after correction for domestic indoor air quality. These data support evidence for an increased prevalence of respiratory disease in populations exposed to cotton dust.

Adult↗
PubMed1994

[Effect of panaxadiol saponin (PDS) on phorbol ester induced change of protein kinase C activity in cardiomyocytes].

Partially purified protein kinase C and protein kinase A were separately incubated with various concentrations of PDS (1-1000 micrograms.ml-1) for 10 min in vitro. The results indicate that protein kinase C activity was inhibited in a dose-dependent manner by PDS, but type I and type II protein kinase A were not. In cardiomyocytes preincubated with PDS (250, 500, 1000 micrograms.ml-1) for 10 min, PMA-induced decrease of cytosol protein kinase C activity and increase of membrane protein kinase C activity were greatly inhibited in the same manner. These results suggest that PDS not only inhibited protein kinase C in vitro, but also inhibited activation of protein kinase C in cardiomyocytes.

Animals↗
PubMed1992

Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.

Air Pollutants, Occupational↗
PubMed1992

Sequencing and population analysis of four novel HLA-DPA1 alleles.

We determined the base sequences of the HLA-DPA1 gene from four B-lymphoblastoid cell lines (CB6B, LKT3, AMAI, and T7526) that showed distinct electrophoretic patterns of single-stranded polymerase chain reaction products of the HLA-DPA1 gene. The novel HLA-DPA1 alleles of CB6B, LKT3, AMAI, and T7526 were designated DPA1*02021, DPA1*02022, DPA1*0301, and DPA1*0401, respectively. Although there was only one base substitution between DPA1*02021 and DPA1*02022, the single-strand conformation polymorphism of these two alleles was clearly demonstrated by electrophoresis in a nondenaturing polyacrylamide gel containing 10% glycerol. In addition, we genotyped for the HLA-DPA1 gene of healthy unrelated Oriental individuals--i.e., 227 Japanese, 88 Papua New Guineans, and 41 Buyi-Chinese--to demonstrate the ethnic distribution of the HLA-DPA1 alleles.

Alleles↗
PubMed1991

Decreased transient outward K+ current in ventricular myocytes from acromegalic rats.

Cardiac hypertrophy and heart failure are common to acromegalic patients who have abnormally high serum growth hormone (GH). While the function of cardiac muscle is clearly affected by chronically elevated GH, the electrical activity of myocytes from hearts with GH-dependent hypertrophy has not been studied. We used adult, female Wistar-Furth rats with induced GH-secreting tumors to study the effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors were induced by subcutaneous inoculation of GH3 cells. Eight weeks after inoculation, the rats had doubled their body weight and heart size compared with age-matched controls. There were no differences in either action potential amplitude or resting potential of right ventricular myocytes from control and tumor-bearing rats. However, action potential duration increased significantly in tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10) compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action potential was mainly due to a decrease in density of a transient outward current (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/- 0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing rats. The decrease in It,o) and increase in heart weight occurred with a similar time course. The increased action potential duration prolongs Ca2+ influx through L-type Ca2+ channels in the tumor-bearing animals; this may be important in cardiovascular adaptation.

Acromegaly↗
PubMed1991

Prevalence of hepatitis B virus infection markers among factory workers in Beijing, China.

Nearly 1,000 serum samples were obtained from apparently healthy workers of both sexes in various factories in Beijing during 1988-1989 and were examined for hepatitis B virus infection markers by radioimmunoassay. The overall prevalence (all ages and both sexes combined) of cases positive for HBsAg, anti-HBs and anti-HBc were 3.7%, 36.6% and 37.7%, respectively and the rate of those negative to any of the three markers studied was 56.1%. The infection rate was lower than the values reported early in the 1980s for Beijing populations or the values for populations in other parts of China.

Adolescent↗
PubMed1990

Increase in T-type calcium current in atrial myocytes from adult rats with growth hormone-secreting tumors.

Growth hormone (GH) has pronounced effects on protein synthesis and cell growth in cardiac muscle from adult animals, although the mechanism of its action is not understood. Because Ca2+ has been implicated as a regulator of mitogenic processes in a number of tissues, we investigated whether GH affects the transmembrane movement of Ca2+ through voltage-activated channels of cardiac myocytes. Atrial and ventricular myocytes were isolated from adult rats with GH-secreting tumors and studied electrophysiologically by using patch-clamp techniques. Tumor-bearing rats re-enter an active growth phase and double their body weight over age-matched controls 8 weeks after introduction of the tumor. Atrial myocytes from tumor-bearing animals showed a 3-fold increase in the density of T-type Ca2+ current compared with cells from control animals, although the voltage dependency of activation and inactivation of T-type current was not altered. The increase in T-current density of atrial myocytes preceded by at least a week any measurable change in heart weight, body weight, or myocyte size. L-type Ca2+ currents in atrial and ventricular cells were not affected. The results suggest that a tumor-derived growth factor, most likely GH, can cause a specific enhancement of T-type Ca2+ current in atrial myocytes.

Animals↗
PubMed1990

Longitudinal and cross-sectional estimates of pulmonary function decline in never-smoking adults.

This paper describes methods for simultaneous cross-sectional and longitudinal analysis of repeated measurements obtained in cohort studies with regular examination schedules, then uses these methods to describe age-related changes in pulmonary function level among nonsmoking participants in the Six Cities Study, a longitudinal study of air pollution and respiratory health conducted between 1974 and 1983 in Watertown, Massachusetts; Kingston and Harriman, Tennessee; St. Louis, Missouri; Steubenville, Ohio; Portage, Wisconsin; and Topeka, Kansas. The subjects, initially aged 25-74, were examined on three occasions at 3-year intervals. Individual rates of loss increased more rapidly with age than predicted from the cross-sectional model. For example, for a male of height 1.75 m, the cross-sectional model predicted an increase in the annual rate of loss of FEV1 from 23.7 ml/yr at age 25 to 39.0 ml/yr at age 75, while the longitudinal model gave rates of loss increasing from 12.9 ml/yr at age 25 to 58.2 ml/yr at age 75. These results contrast with those of other studies comparing longitudinal and cross-sectional estimates of pulmonary function loss.

Adult↗
PubMed1989

Risk factors in chronic obstructive pulmonary malfunction and "chronic bronchitis" symptoms in Beijing district: a joint study between Japan and China.

A cross sectional study of risk factors in respiratory diseases was carried out in August 1986, in Beijing, China. Inhabitants greater than or equal to 40 years old were selected at random from a rural area, a residential area and an industrial area, using a two stage sampling method. The analysis presented here is based on the sample population of adults who (1) were prepared to be interviewed, using the British Medical Research Council's questionnaire translated into Chinese (n = 3423) and (2) had lung function measurements at the same time (n = 3373). Obstructive lung disease was defined as forced expiratory volume in 1s (FEV1) less than 68% of forced vital capacity (FVC). Seven variables were considered as potential risk factors or confounding factors: area of residence, sex, age, cigarette smoking, history of respiratory disease, socio-economic status and familial component. A modified binary variable regression method developed by Feldstein was used for the adjustment of rate ratios. The adjusted prevalence of obstructive lung disease was highest in the rural area and lowest in the residential area(s). An increase in age, cigarette smoking, low socio-economic status and positive history of respiratory diseases were associated with significantly higher rates of impaired pulmonary function. The other measured factors did not appear to be related to impaired pulmonary function.

Adult↗