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Biomedical subjects

W Y Zhang

Publications and source records attributed to W Y Zhang.

At least 19 recordsLinked to original sources

The common -318C/T polymorphism in the promoter region of CTLA4 gene is associated with reduced risk of ophthalmopathy in Chinese Graves' patients.

Studies in the past have clearly established that CTLA4 is a susceptible gene for Graves' disease (GD). However, association studies between CTLA4 and the risk of developing Graves' ophthalmopathy (GO) in GD patients have shown conflicting results. In this study, associations of five CTLA4 single nucleotide polymorphisms (-1722A/G, -1661A/G, -318C/T, +49G/A, CT60) with GD risk and GO susceptibility in GD patients were investigated in a Chinese population. Our results showed that either +49A/G or CT60 polymorphism was associated with GD susceptibility in the Chinese population. Significant differences in the distribution of the genotypes or alleles evaluated between GD patients with and without clinically evident GO were only found for -318C/T polymorphism (P = 0.03). Multiple logistic regressions revealed that the -318T allele was negatively associated with GO under both additive and dominant genetic models (adjusted OR = 0.56, 95%CI 0.35-0.89, P = 0.014; adjusted OR = 0.51, 95%CI 0.30-0.84, P = 0.009, respectively). Stratification analysis according to gender demonstrated different scenarios concerning the role of the -318T allele in GO risk: a significant protective role for GO was only confirmed in male but not in female GD patients. Haplotype analyses showed that only the haplotypes containing the -318T allele played a protective role in GO. In conclusion, results from this study suggested that the -318T allele might play a protective role in GO susceptibility for GD patients at least in the Chinese population. However, extended analyses with larger sample size should be carried out in patients from different ethnic origins to further verify this association.

Adult↗

Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats.

Ruxiang (Gummi olibanum), the dried gum resin of Boswellia carterii (BC), has been used in traditional Chinese medicine to alleviate pain and inflammation for thousands of years. In this random, blinded study, the anti-arthritic effects of a BC extract were observed and compared to vehicle control in a Lewis rat adjuvant arthritis model (n=8/group). Arthritis was induced by injecting CFA subcutaneously into the base of the tail, and the extract was administered orally (i.g.) for 10 consecutive days beginning on day 16 after the injection. Arthritic scores, paw edema, and the local tissue pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) were assessed. Toxicity and adverse effects of the extract were evaluated. At 0.90 g/kg per day, BC significantly decreased arthritic scores between days 20 and 25 (p<0.05) and reduced paw edema on days 18, 20 and 22 compared to control (p<0.05). It also significantly suppressed local tissue TNF-alpha and IL-1beta (p<0.05). No major adverse effects were observed in animals during the repeated-dose treatment profile although mild fur discoloration was noted. The data show that BC extract has significant anti-arthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines.

Animals↗

Humoral and cellular immune responses to Fasciola gigantica experimental infection in buffaloes.

Humoral and cellular immune responses to Fasciola gigantica experimental infection in buffaloes were studied. The results showed that 33.4+/-9.1% of the infection dose was recovered as adult flukes from infected animals at necropsy. Significant differences of weight gain between infected and non-infected buffaloes was observed at 4 MPI (months post-infection). Anti F. gigantica excretory-secretory products (FgESP)-IgG levels increased significantly from 3 WPI (weeks post-infection) and displayed a peak at 13 WPI. Western blot indicated that in FgESP six major bands of 11.5, 19.0, 23.4, 29.8, 47.5 and 53.2kDa were recognized by F. gigantica-infected buffaloes sera after 0 WPI. Eosinophil numbers increased significantly from 3 WPI in F. gigantica-infected buffaloes and displayed a peak at 8 WPI. Peripheral blood mononuclear cells (PBMC) proliferation induced by FgESP increased from 2 WPI with a peak at 5 WPI. IFNgamma secretion by FgESP-stimulated PBMC appeared early from 1 WPI with three peaks at 2, 5 and 8 WPI, respectively. IL-10 production was observed from 2 WPI with two peaks at 4 and 9 WPI, respectively. Our results suggested that buffaloes were highly susceptible to F. gigantica infection, and this susceptibility could be associated with the late and weak cellular immune response in the early phase of infection and the Th0-like response throughout the infection.

Animals↗

Fasciola hepatica and Fasciola gigantica: comparison of cellular response to experimental infection in sheep.

Cellular responses to Fasciola gigantica and to Fasciola hepatica infection in sheep were compared. Eosinophil numbers increased more quickly and strongly in F. gigantica-infected sheep than in F. hepatica-infected sheep. In both groups, peripheral blood mononuclear cell (PBMC) proliferation in response to the parasitic excretory-secretory products (ESP) showed similar kinetics. Interferon-gamma (IFN-gamma) production by ESP-stimulated PBMC was early and showed similar kinetics in both groups. Interleukin-10 (IL-10) production by FhESP-stimulated PBMC was very high throughout infection even at 0 weeks post-infection (WPI) in F. hepatica-infected sheep, while in F. gigantica-infected sheep, IL-10 production by FgESP-stimulated PBMC increased between 1 and 4 WPI. IL-10 production in F. gigantica-infected sheep was significantly lower than in F. hepatica-infected sheep during infection. The lower susceptibility to F. gigantica infection in sheep could be explained by the more intense cellular response induced by the parasite and the weaker capacity of F. gigantica to evade the immune response.

Animals↗

Preparation of metallodielectric composite particles with multishell structure.

In this article, we demonstrated the synthesis of metallodielectric composite particles comprising a metal shell on a dielectric core and an outer coating of an insulating dielectric layer by depositing silver on silica supporting cores followed by coating of titania. A combination of surface reaction and surface seeding techniques is exploited for the formation of a complete silver shell on silica spheres. The additional outer coating of titania on silver shell particles is then performed by hydrolyzing tetra-n-butyl titanate in ethanol at room temperature. The morphologies of silver shells and titania coating are studied with electron microscopy, and their existences are confirmed with X-ray diffraction and energy-dispersive X-ray measurement.

Journal Article↗

Optical properties of inverted opal photonic band gap crystals with stacking disorder.

We present a detailed study of the effect of planar stacking disorder on optical properties of inverted opal photonic crystals. Systems with periodic stacking sequences are first studied that include face centered cubic, hexagonal close-packed, and doubly hexagonal close-packed photonic crystals. For the structures with periodic stacking order, we evaluate the band structure followed by calculation of transmission spectrum along the direction perpendicular to the hexagonal close-packing plane of the structures. Inverted opal photonic crystals with random stacking sequences are then studied by calculating average transmittance of the photonic crystal slabs over various random stacking configurations. The position and width of the lowest stop gap along the direction normal to the hexagonal close-packing plane is found to be invariant, regardless of the stacking sequence in the photonic crystal. We show how the propagation properties at higher frequencies are affected by the stacking configurations (both periodic and disordered stacking sequences), particularly those near the edges of the absolute band gap. The obtained results are directly relevant to transmission/reflection experiments on inverted opal photonic crystals with complete band gap.

Journal Article↗

Mutations in the hepatocyte nuclear factor-1alpha gene in Chinese MODY families: prevalence and functional analysis.

AIMS/HYPOTHESIS: Maturity-onset diabetes of the young is an autosomal dominant form of diabetes characterised by an early age of onset (usually <25 years). We investigated the prevalence and trans-activating activity of hepatocyte nuclear factor (HNF) -1 alpha mutations in southern Chinese families with MODY. METHODS: We screened for mutations in the HNF-1 alpha gene in 50 unrelated southern Chinese families, which fulfilled the minimum criteria for MODY. Functional properties of the mutant proteins were investigated using site-directed mutagenesis and luciferase reporter assay. RESULTS: Five of the 50 (10%) families were found to have mutations in the coding region, including a new nonsense mutation Q176X and four reported mutations (frameshift mutation P379fsdelCT, nonsense mutation R171X, missense mutations G20R and P112L). These mutations had decreased trans-activating activity on the human insulin gene promoter. We also detected a new intronic sequence variation IVS7nt-6 G-->A, which co-segregated with diabetes. The intronic variation creates a potential splice acceptor site and might alter the splicing of the HNF-1 alpha mRNA. CONCLUSION/INTERPRETATION: Mutations in the HNF-1 alpha gene seem to be an important cause of MODY in southern Chinese. The mutations could affect normal islet function by altering the expression of target genes.

Amino Acid Substitution↗

Three-dimensional optical trajectory tracing and energy deposition of a laser beam in a laser-driven fusion.

A convenient method of three-dimensional ray tracing is suggested in the geometrical optical approximation, in which the laser ray propagation is completely based on the concept of optical trajectory tracing rather than depending upon the effective force and propagation time. This tracing has two obvious advantages that the direct application of Snell's law can be avoided when a ray crosses a different density zone and that to any desired accuracy it takes much less computation time than existing tracing. For Gaussian light beam propagation, in a spherically symmetric plasma atmosphere, the results emphasize that the deposition uniformity is strongly dependent not only on the wavelength of the laser but also on the temperature of the plasma.

Journal Article↗

A mimotope of pre-S2 region of surface antigen of viral hepatitis B screened by phage display.

To acquire the phage-displayed mimotopes which mimic the specificity of hepatitis B virus surface antigen (HBsAg), a random peptide library expressing linear peptide with 12 amino acids in length were used to screen with the serum from a hepatitis B virus infected patient in the recovery phase. After 3 rounds of biopanning, the positive phages were confirmed by competitive ELISA using HBsAg/P33. Two phagotopes were identified and one of them was confirmed as mimotope by competition experiment. Based on the mimotpe, a multiple antigenic peptide with four branches was synthesized by solid phase peptide synthesis. The antiginicity and specificity of the synthesized antigen was tested in BALB/c mice compared with the native epitope-based antigen. The results showed that the mimotope-based antigen could evoke higher titer of antibodies with the same specificity of the epitope-based antigen. Those findings indicate mimotopes can be used in antigen and vaccine design.

Animals↗

Surfactant and inhaled nitric oxide in rats alleviate acute lung injury induced by intestinal ischemia and reperfusion.

BACKGROUND: Respiratory distress and acute lung injury (ALI) are severe complications of intestinal ischemia and reperfusion injury (I/R). The authors hypothesize that a combined surfactant and inhaled nitric oxide (iNO) may alleviate I/R-induced ALI. METHODS: Adult rats (body weight 285 to 315 g, n = 45) were allocated randomly to either a negative control group (N-Control, n = 9) with only sham laparotomy, or groups (n = 9 each) for induction of I/R by occlusion of superior mesenteric artery, followed by treatment with (1) surfactant at 100 mg/kg (Surf), (2) iNO at 20 ppm (NO), (3) both surfactant and iNO (SNO), or (4) no surfactant no iNO (a positive control, P-Control). Mechanical ventilation was provided for 120 minutes with variable peak insufflation pressure and FIO2 to achieve adequate arterial pH, PaO2, and PaCO2. Blood gas values, dynamic lung compliance (Cdyn), and airway resistance (Raw) were measured during the 2-hour treatment. Lung wet-to-dry weight ratio (W/D), histopathology, and morphometric analysis of alveolar expansion (V(V)) were determined at the end of the experiment. RESULTS: After 120 minutes of treatment, the SNO group had the highest PaO2 and Cdyn values, close to that of the N-Control group. The Surf, NO, and SNO groups had higher V(V) and lower CV (V(V)) values than the P-Control, but modest decrease of W/D values. The NO group had moderately improved PaO2 but Cdyn and V(V) were as low as that of the P-Control. The lungs of the SNO group had significantly alleviated edema and neutrophil infiltration compared with the P-Control. CONCLUSIONS: The combined surfactant and iNO treatment alleviated rat ALI induced by I/R, and exerted effects better than the use of surfactant or iNO alone.

Administration, Inhalation↗

New 2-(2-phenylethyl) chromones from Bothriochloa ischaemum.

Two new 2-(2-Phenylethyl) chromones were isolated from Bothriochloha ischaemum (Gramineae). They were characterized as 5-hydroxy-6-methoxy-2-[2-(2-hydroxyphenyl)-ethyl]-chromone(1) and 5-hydroxy-2-[2-(2-hydroxyphenyl)-ethyl]-chromone(2) by means of spectroscopic analysis, especially 2D-NMR experiments.

China↗

Meta-analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension.

AIM: To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs). METHODS: Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects. RESULTS: Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6). CONCLUSION: This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.

Adrenergic beta-Antagonists↗

A benefit-risk assessment of caffeine as an analgesic adjuvant.

Caffeine has been an additive in analgesics for many years. However, the analgesic adjuvant effects of caffeine have not been seriously investigated since a pooled analysis conducted in 1984 showed that caffeine reduces the amount of paracetamol (acetaminophen) necessary for the same effect by approximately 40%. In vitro and in vivo pharmacological research has provided some evidence that caffeine can have anti-nociceptive actions through blockade of adenosine receptors, inhibition of cyclo-oxygenase-2 enzyme synthesis, or by changes in emotion state. Nevertheless, these actions are only considered in some cases. It is suggested that the actual doses of analgesics and caffeine used can influence the analgesic adjuvant effects of caffeine, and doses that are either too low or too high lead to no analgesic enhancement. Clinical trials suggest that caffeine in doses of more than 65 mg may be useful for enhancement of analgesia. However, except for in headache pain, the benefits are equivocal. While adding caffeine to analgesics increases the number of patients who become free from headache [rate ratio = 1.36, 95% confidence interval (CI) 1.17 to 1.58], it also leads to more patients with nervousness and dizziness (relative risk = 1.60, 95% CI 1.26 to 2.03). It is suggested that long-term use or overuse of analgesic medications is associated with rebound headache. However, there is no robust evidence that headache after use or withdrawal of caffeine-containing analgesics is more frequent than after other analgesics. Case-control studies have shown that caffeine-containing analgesics are associated with analgesic nephropathy (odds ratio = 4.9, 95% CI 2.3 to 10.3). However, no specific contribution of caffeine to analgesic nephropathy can be identified from these studies. Whether caffeine produces nephrotoxicity on its own, or increases nephrotoxicity due to analgesics, is yet to be established.

Adjuvants, Pharmaceutic↗

Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking.

The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The cholesterol microdomains were visualized with a monoclonal antibody that specifically detects ordered cholesterol arrays. These unique cholesterol microdomains were induced on macrophages and fibroblasts when they were enriched with cholesterol in the presence of an ACAT inhibitor, to block esterification of excess cellular cholesterol. Induction of the plasma membrane cholesterol microdomains could be blocked by agents that inhibit trafficking of cholesterol to the plasma membrane and by cholesterol acceptors that remove cholesterol from the plasma membrane. In addition, plasma membrane cholesterol microdomains did not develop in mutant Niemann-Pick type C fibroblasts, consistent with the defect in cholesterol trafficking reported for these cells. The induction of plasma membrane cholesterol microdomains on inhibition of ACAT helps explain how ACAT inhibition promotes cholesterol efflux from cells in the presence of cholesterol acceptors such as HDL. The anti-cholesterol monoclonal antibody also detected extracellular cholesterol-containing particles that accumulated most prominently during cholesterol enrichment of less differentiated human monocyte-macrophages. For the first time, cholesterol microdomains have been visualized that function in cholesterol trafficking to and from the plasma membrane.

Animals↗

Effects of depressed myocardial contractility induced by microgravity on cardiovascular response to orthostatic stress: a computer simulation.

The aim of present study is to investigate the role played by the depression of myocardial contractility in the mechanism of cardiovascular deconditioning and orthostatic intolerance (OI) induced by space weightlessness. Based on our previous model, which was used to simulate cardiovascular response to lower body negative pressure (LBNP), we incorporated the factor of changes of myocardial contractility into the model by multiplying a coefficient to the time-varying elastance that represents the changes of cardiac contractility. By decreasing the coefficient progressively, we simulated the changes of heart rate (HR), blood pressure (BP), and cardiac output (CO) during LBNP after 0-30% of myocardial contractility depression combined with 12% decrease of the total blood volume. Simulation results indicate that depressed myocardial contractility induces more augment of HR, and more decrement of BP and CO during LBNP and suggest that the depression of myocardial contractility degenerate cardiovascular response to orthostatic stress.

Blood Pressure↗

Coinduction of inducible nitric oxide synthase and arginine recycling enzymes in cytokine-stimulated PC12 cells and high output production of nitric oxide.

Nitric oxide (NO) is involved in many physiological and pathological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS), and the citrulline generated as a by-product can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) via the citrulline-NO cycle. When neuronal PC12 cells differentiated with nerve growth factor were treated with interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), iNOS and AS mRNAs and proteins were markedly induced, with AL mRNA and protein being weakly induced. Cationic amino acid transporter-1 and -2 were not induced. IFNgamma or TNFalpha alone was ineffective. A large amount of NO (190 microM NO(2)(-) plus NO(3)(-) in culture medium in 24 h) was produced from arginine by cytokine-stimulated cells, and arginine could be replaced by citrulline. iNOS induction and NO production were attenuated by dexamethasone and dibutyryl cAMP and even more strongly so when combined. Therefore, a large amount of NO is produced in cytokine-stimulated PC12 cells following to induction of iNOS and citrulline-arginine recycling is important for NO production.

Animals↗

Plasmin-mediated macrophage reversal of low density lipoprotein aggregation.

Evidence suggests that aggregated low density lipoprotein (AgLDL) accumulates in atherosclerotic lesions. Previously, we showed that AgLDL induces and enters surface-connected compartments (SCC) in human monocyte-derived macrophages by a process we have named patocytosis. Most AgLDL taken up by these macrophages in the absence of serum is stored in SCC and remains undegraded. We now show that macrophages released AgLDL (prepared by vortexing or treatment with phospholipase C or sphingomyelinase) from their SCC when exposed to 10% human lipoprotein-deficient serum (LPDS). Macrophages also took up AgLDL in the presence of LPDS, but subsequently released it. In both cases, the released AgLDL was disaggregated. Although the AgLDL that macrophages took up could not pass through a 0.45-micrometer filter, >60% of AgLDL could pass this filter after release from the macrophages. Disaggregation of AgLDL was verified by gel-filtration chromatography and electron microscopy that also showed particles larger than LDL, reflecting fusion of LDL that aggregates. The factor in serum that mediated AgLDL release and disaggregation was plasmin generated from plasminogen by macrophage urokinase plasminogen activator. AgLDL release was decreased >90% by inhibitors of plasmin (epsilon-amino caproic acid and anti-plasminogen mAb), and also by inhibitors of urokinase plasminogen activator (plasminogen activator inhibitor-1 and anti-urokinase plasminogen activator mAb). Moreover, plasminogen could substitute for LPDS and produce similar macrophage release and disaggregation of AgLDL. Because only plasmin bound to the macrophage surface is protected from serum plasmin inhibitors, interaction of AgLDL with macrophages was necessary for reversal of its aggregation by LPDS. The released disaggregated LDL particles were competent to stimulate LDL receptor-mediated endocytosis in cultured fibroblasts. Macrophage-mediated disaggregation of aggregated and fused LDL is a mechanism for transforming LDL into lipoprotein structures size-consistent with lipid particles found in atherosclerotic lesions.

Cell Membrane↗