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Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 163 records · Page 9Linked to original sources

Mouse model of transplant arteriosclerosis: role of intercellular adhesion molecule-1.

Transplant-accelerated arteriosclerosis in coronary arteries is the major limitation to long-term survival of patients with heart transplantation. The pathogenesis of this disease is not fully understood. Herein, we describe a simplified model of artery allografts in the mouse that allows us to take advantage of transgenic, knockout, or mutant animals. Common carotid arteries or aortic vessels were end-to-end allografted into carotid arteries between C57BL/6J and BALB/c mice. Neointimal lesions were observed as early as 2 weeks after surgery and had progressed at 4 and 6 weeks postoperatively. The lumen of grafted arteries was significantly narrowed due to neointima hyperplasia 4 weeks after transplantation. Using this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of transplant arteriosclerosis in ICAM-1-deficient mice. Neointimal lesions of artery grafts from ICAM-1 -/- C57BL/6J to BALB/c mice were reduced up to 60% compared with wild-type controls. MAC-1 (CD11b/18)-positive cells adhering to the surface of ICAM-1 -/- artery grafts were significantly less as identified by en face immunofluorescence, and these positive cells were more abundant in intimal lesions of artery grafts in wild-type mice. Furthermore, the major cell component of neointimal lesions 4 weeks after surgery was found to be alpha-actin-positive smooth muscle cells, which were significantly reduced in lesions of ICAM-1 -/- artery grafts. Thus, this model has been proven to be useful for understanding the mechanism of transplant arteriosclerosis. Our findings demonstrate that ICAM-1 is critical in the development of allograft arteriosclerosis via mediation of leukocyte adhesion to, and infiltration into, the vessel wall.

Actins↗

Fluid shear stress induces heat shock protein 60 expression in endothelial cells in vitro and in vivo.

Recent investigations indicate that the initial event in the pathogenesis of atherosclerosis involves an (auto)immunologic injury to the vessel wall. Heat shock proteins (hsps), which are expressed on the endothelial cell surface, constitute possible autoantigens. After being exposed to shear stress of 30 dyne/cm(2) in vitro by means of a rotational viscometer, human umbilical vein endothelial cells were immunohistochemically stained for hsp 60 by the monoclonal antibody ML-30; static control cells were negative. Maximal hsp 60 induction was observed after 12 hours of hemodynamic stress. In Northern blots, the level of hsp 60 mRNA was markedly increased after only 1 hour of shear stress in human umbilical vein endothelial cells compared with static control cells. In vivo investigations in Lewis rats confirmed these in vitro findings: the intima and media of frozen sections of the right common carotid artery exposed to increased wall shear stress (after ligation of the left common carotid artery) were stained for hsp 60. The vessel wall of the left low-shear-stress-exposed side was negative. These findings demonstrate that shear stress results in hsp 60 induction in endothelial cells in vivo and in vitro, providing the prerequisite for humoral and cellular reactions to endothelial hsp in the earliest stages of atherosclerosis.

Animals↗

Ras/Rac-Dependent activation of p38 mitogen-activated protein kinases in smooth muscle cells stimulated by cyclic strain stress

p38, a subfamily of the mitogen-activated protein kinases (MAPKs), is a crucial signal transducer between a variety of extracellular stimuli and gene expression in mammalian cells. This kinase is activated in cultured cells stimulated by heat shock, osmotic stress, and proinflammatory cytokines, but a similar activation of p38 MAPKs in vascular smooth muscle cells (SMCs) stimulated by mechanical stress has yet to be studied. We studied signal pathways leading to time- and strength-dependent p38 activation in rat SMCs in response to cyclic strain stress. p38 phosphorylation in stressed SMCs showed maximal activation at 10 minutes. This activation was significantly inhibited by pretreatment of the SMCs with pertussis toxin, a G-protein antagonist, and enhanced by treatment with suramin, a growth factor receptor antagonist, but opposite effects in the activation of extracellular signal-regulated kinases stimulated by mechanical forces were found. p38 activation was markedly reduced in stressed SMCs after protein kinase C depletion. Interestingly, SMC lines stably expressing dominant-negative ras (ras N17) or rac1 (rac1 N17) almost abolished p38 phosphorylation induced by cyclic strain stress. When p38 activation was inhibited by the specific inhibitor SB 202190, SMC migration, determined in a Boyden chamber in response to stimulation with platelet-derived growth factor-BB, and SMC proliferation, stimulated by cyclic strain stress, were abrogated. Thus, we provide the first evidence that cyclic strain stress rapidly activates p38 MAPKs via activation of protein kinase C ras/rac signal pathways, suggesting that p38 MAPKs are important signal transducers mediating the mechanical stress-induced cell responses essential for SMC migration and proliferation.

Journal Article↗

No association between dehydroepiandrosterone sulfate and development of atherosclerosis in a prospective population study (Bruneck Study).

Antiatherogenic properties of dehydroepiandrosterone (DHEA) have been postulated for >40 years. Large-scale epidemiological studies on this important issue, however, are still sparse, and those available have yielded contradictory results. The Bruneck Study involved a large random sample of men and women aged 40 to 79 years that were enrolled in 1990 and reevaluated 5 years later. Baseline DHEA sulfate (DHEAS) levels were measured in 867 subjects after an overnight fast. Development and progression of carotid atherosclerosis was monitored by high-resolution duplex ultrasound. DHEAS levels declined with advancing age (29% and 44% per decade in men and women) and showed a complex sex-specific association with various vascular risk attributes and factors conferring protection against atherosclerosis. Age- and sex-adjusted DHEAS baseline levels did not differ between subjects with or without incident/progressive atherosclerosis (geometric mean 1161 versus 1253 microg/L). After adjustment for vascular risk factors and potential confounders, the odds ratio of incident/progressive atherosclerosis comparing a 50% increase in DHEAS levels was 0.99 (95% CI 0.89 to 1.11). Lack of an association between DHEAS and atherogenesis was confirmed in sex-specific and a variety of supplementary analyses. Statistical power would be high enough to detect differences in DHEAS between outcome categories as low as 15% (alpha=0.05). This prospective community-based study does not support a role for endogenous DHEA(S) in the development of human atherosclerosis.

Adult↗

A SXRF method for determining the relative concentration of trace elements in plasma protein affected by cisplatin.

This article presents an analytical method for the determination of the relative concentrations of trace elements in plasma protein by gel chromatography combined with SXRF (synchrotron radiation X-ray fluorescence). The fraction of plasma protein of male Kunming mice (body weight 24.2 +/- 0.3 g), treated with a cisplatin i.p. injection at a dose of 10 mg/kg, was obtained by the separation of a Sephadex G-50 column (buffered with ammonium acetate, pH 5.7). The SXRF experiments were performed at the Beijing Electron Positron Collider synchrotron radiation facility. The elements (Pt, S, Ca, Fe, Ni, Cu, Zn, Se, Br, and Sr) in the fraction of the plasma proteins (>22 kDa) were assayed using highly sensitive SXRF. The relative concentrations of elements were calculated by a normalization of Compton scattering intensity around 22 keV, after the normalization for the collection time of the X-ray spectrum and the counting of the ion chamber, and subtracting the contribution of the polycarbonate film for the supporting sample. The determination could prove that the element Pt in plasma was bound with macromolecular protein. Cu and S were present in the fraction of the protein in mice treated with cisplatin increase, and their ratios of treated/control were 1.66 +/- 0.06 and 1.78 +/- 0.33, respectively; Zn decreased to a ratio of 0.78 +/- 0.09. Our results are in agreement with others that cisplatin exposure leads to a marked loss of kidney copper and a moderate rise in kidney zinc. However, this article primarily describes one of the analytical methods used; it does not emphasize the results of the effect of cisplatin on trace elements in plasma protein.

Animals↗

[Background analysis of chromosome controling genetic of water use efficiency of Triticum].

Water use efficiency (WUE) of flag leaf of different genetic material was measured by LCA-3 model photosynthesis apparatus. The results show as follows: The order of flag leaf WUE of different chromosome set is AA > BB > DD > RR. Among twenty Chinese Spring ditelosomic, the flag leaf WUE of A ditelosomic set is the highest, the high WUE genes locate on 1AL, 2AL, 2AS and 7AS chromosome arm. Among seven wheat-S. Cereals addition lines, the high WUE gene locates on 4R chromosome, the flag leaf WUE of 5R chromosome is the lowest. In the end of this paper, the research advance of stress resistance gene location on the fourth chromosome set of Triticum was discussed.

Chromosome Mapping↗

[Reciprocal modification of Fas activation and stress protein response decides apoptosis or resistance development of cells].

Activation of heat shock factor (HSF)-1 DNA binding and heat shock protein (hsp)-70 expression enable resistance of cells to various forms of stress and maintain cell survival. Fas, a membrane-bound protein, is a central pro-apoptotic factor. Its activation leads to a cascade of events resulting in programmed cell death. Herein, these two mechanisms with contrary functions, promoting either cell survival or death, were addressed for their potential to inhibit each other's activation. Induction of Fas-mediated signalling was followed by a rapid decrease of HSF1 DNA binding and inducible hsp70 expression. Inhibition of HSF1 DNA binding was demonstrated to be based on absent hyperphosphorylation of HSF1 during FAS-signalling. These effects of Fas-activation on the HSF1/hsp70 stress response were blocked by ICE (caspase 1)-inhibitors, suggesting an ICE-mediated process. Furthermore, inhibition of HSF1/hsp70 was accompanied by an increase of apoptosis rates from 20% to 50% in response to heat stress. When analyzing Fas-mediated apoptosis in the presence of HSF1/hsp70 activation, decreased apoptosis rates were detected with induced expression of hsp70 but not with activation of HSF1-DNA binding alone. Thus, we conclude that inhibition of the HSF1/hsp70 stress response during Fas-mediated apoptosis and vice versa may facilitate a cell to pass a previously chosen pathway, stress resistance or apoptosis.

Animals↗

[Studies on the production of 16 beta-methyl-11 alpha,17 alpha,21-trihydroxy-1,4-pregnadiene-3,20-dione from 16 beta-methyl-17 alpha,21-dihydroxy-1,4-pregnadiene-3,20-dione-21-acetate by Absidia].

An Absidia sp. 28 strain was shown to have higher activity of 11 alpha-hydroxylation using 16 beta-methyl-17 alpha,21-dihydroxy-1,4-pregnadiene-3,20-dione as a substrate. It was found that 21-acetylization of substrate could increase 11 alpha-hydroxylation rate conspicuously. The yield of the 11 alpha-hydroxylation by this strain was 73% in the conversion of 0.5% concentration of 21-acetated substrate under optimum conditions.

Absidia↗

Estimation of burden of disease for smear-positive pulmonary TB and its infectivity.

The study investigated the burden of smear-positive pulmonary TB and its infectivity, using DALY (Disability-Adjusted Life Year) as an indicator. An assumed cohort of 2000 cases was set up based on the age-specific incidence of 794 newly registered smear positive cases of TB in Beijing in 1994. Prognostic trees and model diagrams of infectivity under natural history and DOTS (Direct Observed Treatment, Short-course) strategy were established according to the epidemiological evidence. The results show that 29.6% of DALYs would be neglected if the burden caused by the infectivity was not considered. The results also show that DOTS strategy may reduce 97.3% of the number of potential cases infected, 92.9% of DALYs related to TB-patients themselves, and 99.9% of DALYs caused by TB's infectivity as well.

Adolescent↗

Effects of angiotensin II receptor blockade on hepatic fibrosis in rats.

OBJECTIVE: To investigate the effects of angiotensin II type 1 receptor blockade, losartan, on serum levels of components of extracellular matrix in experimental fibrotic rats. METHODS: Fifty male Spague-Dawley rats were separated into five groups (control, model, and 3 treatment groups). Excepting rats in control group, all rats were given subcutaneous injection of 40% carbon tetrachloride (once every 3 days for 6 weeks). Rats in 3 treatment groups were also given losartan of 10mg/kg, 5mg/kg, 2.5mg/kg daily for 6 weeks via gastrogavage, respectively. At the end of sixth week, all rats were sacrificed. Radioimmunoassay was performed to determine the serum levels of hyaluronic acid (HA), Laminin (LN), procollagen type III (PCIII) and collagen type IV. Van Giesion collagen staining was used to evaluate the extracellular matrix of the liver tissue. RESULTS: Compared with model group, losartan significantly reduced the serum levels of HA [from (911.66 +/- 345.49)microg/L to (425.05 +/- 115.80)microg/L], LN [from (209.87 +/- 91.57)microg/L to (83.56 +/- 22.12)microg/L, PCIII [from (31.82 +/- 6.90)microg/L to (22.78 +/- 8.38)microg/L] and collagen IV [from (54.09 +/- 19.81)microg/L to (30.51 +/- 12.39)microg/L] (P<0.05) and greatly attenuated the degree of liver fibrosis (P<0.05). CONCLUSION: Losartan can markedly reduce the serum levels of LN, HA, PCIII and collagen type IV of fibrotic rats induced by CCl(4) and greatly attenuate the degree of liver fibrosis.

Angiotensin Receptor Antagonists↗

[Two different fermentation techniques of steriod 1,4-dehydrogenation and 11 alpha-hydroxylation].

Two kinds of micro-organism, Arthrobacter sp. AX86(1,4-dehdrogenator) and Absidia sp. A28(11 alpha-hydroxylator) were used in this experiment. Two different fermentation techniques were performed to accomplish the multiple conversional reactions for producing 16 beta-methyl-11 alpha,17 alpha,21-trihydroxy-1,4-pregnadiene-3,20-dione(III) from 16 beta-methyl-3 beta,17 alpha,21-trihydroxy-5 alpha-pregnane-20-one-21-acetate(I): 1) To produce product(III) by means of a two-step fermentation method which were independently performed first by Arthrobacter and next by Absiaia, and 2) the product was obtained by a sequential fermentation system of aforesaid two micro-organisms in a single fermentor without isolation of the intermediates from the mixture. Our results showed that in both fermentation systems high yield of product was obtained. However, according to the technical simplicity, shorter duration of fermentation cycle and efficient yield of product, the second method is better than the first one.

Absidia↗

[A quantitative study of poincare dispersed-dot plot for heart rate variability].

Poincare dispersed-dot plot is an important nonlinear dynamics method that can effectively describe the attractor shape. Yet studies in the past generally processed the plot in a graphic mode without further discussion on the quantitative indices. That was not suited for clinical application and studies. So, based on the shape of Poincare dispersed-dot plot, we propose a group of quantitative parameters of Poincare dispersed-dot plot: plot square(SQ), long axis (LA), short axis(SA), and angle related to long-axis and short-axis(ALS). According to the characters of the heart rate Poincare dispersed-dot plot, we have posed the 'tortoise crawling and counting' algorithm to get these four quantitative parameters. We have tested these four quantitative parameters with clinical and animal experiment data. The results demonstrate that these four parameters are of certain specificity to heart diseases, indicating that these parameters might be useful for clinical diagnosis.

Algorithms↗

Cost effectiveness of DOTS and non-DOTS strategies for smear-positive pulmonary tuberculosis in Beijing.

The cost-effectiveness of DOTS (Directly Observed Treatment, short course) and non-DOTS strategies for smear-positive pulmonary tuberculosis in Beijing was evaluated. Cost calculation was based on the expenses of drugs, chest X-ray films, sputum smears and cultures for the patients. Effectiveness of the intervention was assessed in two aspects: direct benefits to the patients treated and indirect benefits to the others through reduced transmission of tuberculosis; disability adjusted life of year (DALY) was used as an index. The results showed that one DALY could be saved with 45.7 Yuan by DOTS and 471.4 Yuan by non-DOTS. DOTS is a good control strategy for smear-positive tuberculosis.

China↗

Impaired gp-91phox gene expression and dysfunction of peripheral blood neutrophils in patients maintaining hemodialysis.

OBJECTIVE: To investigate expressions of gp-91phox and IL-8 gene and the function of neutrophils in hemodialysis (HD) patients, and to understand the relationship between uremia and immune. METHODS: Gene expression was studied by means of reversal transcription polymerase chain reaction (RT/PCR) from the untreated and treated with lipopolysaccharide (LPS) neutrophils in controls and HD patients. Phagocytosis and bactericidal assays were measured as a decrease in the number of viable intracellular and extracellular bacteria by colony counts. RESULTS: Freshly isolated neutrophils express gp-91phox mRNA in controls while no gp-91phox mRNA was detected in HD patients. When challenged with LPS, gp-91phox mRNA exhibited decreased expression. IL-8 mRNA in HD patients could be spontaneously expressed. Phagocytosis and intracellular killing of neutrophils, when exposed to Staphylococcus aureus, were decreased obviously compared with controls. CONCLUSIONS: The impaired gp-91phox gene expression of neutrophils indicates the impaired NADPH-oxidase system and the untreated neutrophils spontaneously express IL-8 mRNA in the HD patients, which is consistent with suppressed phagocytosis and intracellular killing capacity.

Cell Division↗

[AP-1 mediated signal transduction in thrombin-induced regulation of PAL-1 expression in human mesangial cells].

OBJECTIVE: To evaluate activator protein-1 (AP-1) mediated mechanisms in thrombin-induced qlasminogen activator inhibitor-1 (PAI-1) expression in cultured human glomerular mesangial cells (MCs). METHODS: Electrophoretic mobility shift assay (EMSA) was employed to assess AP-1 DNA-binding activity, and Western blot hybridization was used for quantification of c-fos and c-jun, two subunits of AP-1 dimers. PAI-1 activity and mRNA expression were analysed by the fibrin plate assay and Northern hybridization, respectively. RESULTS: Thrombin concentration enhanced PAI-1 activity in the supernatant and stimulated PAI-1 mRNA expression in cultured MCs. PAI-1 activity was blocked by hirudin, a specific inhibitor of thrombin. Further study demonstrated that thrombin promoted AP-1 DNA-binding activity but exerted little effect on c-fos or c-jun. Curcumin (AP-1 inhibitor), staurosporine (PKC inhibitor), and genistein (PTK inhibitor) all reduced AP-1-mediated PAI-1 mRNA expression induced by thrombin in cultured MCs. CONCLUSION: The present study indicates that in cultured human MCs, thrombin stimulates PAI-1 expression through an AP-1 signal pathway, which may be mediated by PKC and PTK.

Cells, Cultured↗

Emodin on hepatic fibrosis in rats.

OBJECTIVE: To investigate effect of emodin on hepatic fibrosis in rats. METHODS: The rat hepatic fibrosis model was induced by the subcutaneous injection of 40% CCl4 (twice a week for 6 weeks) dissolved in olive oil. The emodin-treated rats were treated with low-dose, mediate-dose and high-dose emodin (20, 40 and 80 mg/kg body weight, once a day for 42 days) dissolved in 0.5% sodium carboxymethylcellulose (CMC), except receiving CCl4. Control group received only olive oil and 0.5% CMC. Liver functions were determined by standard procedure. Serum hyaluronic acid and laminin were determined by radioimmunoassay. Liver hydroxyprolines were determined. Histopathological changes were examined by optical microscopy. RESULTS: Compared with model group, the emodin-treated rats showed (1) liver functions were improved, alanine transaminase (ALT) and alkaline phosphatase (AKP) were obviously reduced, and total protein (TP) and albumin (ALB) were significantly increased; (2) serum hyaluronic acid and laminin were markedly reduced; (3) liver hydroxyproline was significantly decreased; (4) the degrees of fibrosis were reduced. The changes of parameters mentioned above were significant (P < 0.05 or P < 0.01). CONCLUSION: Emodin has effect on hepatic fibrosis in rats. The hepatoprotective of emodin may be one of mechanisms for liver fibrosis.

Animals↗

[Influence of androgen on Bcl-2 mRNA expression in BPH tissue].

OBJECTIVE: To study the expression of Bcl-2 mRNA in BPH tissue and the influence of androgen. METHODS: The circulating testosterone level of BPH patients and rats was decreased by administration of medroxyprogesterone and stilbestrol as well as castration. Using RNA dot blot hybridization technic, we detected the Bcl-2mRNA expression in human BPH tissue and rat prostate under different level of androgen. RESULTS: The average dot IOD (integrated optical density, IOD) value ratio of the untreated patient group to the treated group was 1.71 (P < 0.01). There was an decrease of intensity of Bcl-2 mRNA expression in the latter group compared with the former group. The ratio of the normal rat prostates to the castrated rat prostates was 1.28 (P < 0.05). The Bcl-2 mRNA expression was decreased after castration. CONCLUSIONS: The expression of Bcl-2 plays a role in the development of BPH. The decrease of prostatic cell death is important in the BPH pathogenesis. Apart from promoting the proliferation of prostatic epithelia and stroma cells, androgen might prohibit apoptosis by increasing the expression of Bcl-2 in BPH development.

Androgens↗

[Clinical results of transmyocardial laser revascularization for 77 patients with coronary artery disease].

OBJECTIVE: To analyses the clinical results of transmyocardial laser revascularization (TMLR) for 77 patients with coronary artery diseases (CAD). METHODS: The mean age of the patients was (65 +/- 7) years. Previous medical record included CABG (6 patients), PTCA (9), AMI (66.2%), hypertension (70.1%), and diabetes mellitus (45.5%). TMLR was performed on the beating heart via a left anterolateral thoracotomy at the fifth intercostal space. Transesophageal echocardiography showed transmyocardial penetration of 23 +/- 6 channels. RESULTS: The hospital mortality was 3.8%, and postoperative complications were AMI (3.8%), left ventricular failure (2.6%), PVC (5.2%). After operation, the mean CCS angina class was improved from the baseline 3.5 +/- 0.7 to 2.1 +/- 0.3 at 3 months, 1.7 +/- 0.3 at 6 months, 1.7 +/- 0.3 at 12 months and 1.8 +/- 0.4 at 24 months. One patient died of AMI and two died not due to cardiac events during a follow-up of 3 to approximately 24 months. Echocardiography showed that the average of left ventricular ejection fractions was improved significantly at 6 months after operation compared with the preoperative value (P = 0.0457). (201)TI-SPECT showed a remarkable improvement in reversible ischemia in 70% patients followed up. Metabolic stress test for 20 patients followed up patients demonstrated an average increase in exercise tolerance from 7.1 +/- 3.2 min at the baseline to 9.6 +/- 1.3 min at 12 months (P = 0.021). Similarly the METs increased from 4.3 +/- 2.1 at the baseline to 5.4 +/- 2.0 at 12 months. CONCLUSIONS: TMLR is a safe and effective procedure for the treatment of end stage coronary artery diseases not amenable to PTCA or CABG. The effect of TMLR is associated with indication, correct evaluation of myocardial ischemia, and management for postoperative complications.

Aged↗