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Biomedical subjects

G Yao

Publications and source records attributed to G Yao.

At least 19 recordsLinked to original sources

c-Src induces phosphorylation and translocation of p47phox: role in superoxide generation by angiotensin II in human vascular smooth muscle cells.

OBJECTIVE: The aim of this study was to determine molecular mechanisms whereby c-Src regulates angiotensin II (Ang II)-mediated NAD(P)H oxidase-derived *O2- in human vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: VSMCs from human small arteries were studied. Ang II increased NAD(P)H oxidase-mediated generation of *O2- and H2O2 (P<0.01). PP2, c-Src inhibitor, attenuated these effects by 70% to 80%. Immunoprecipitation of p47phox, followed by immunoblotting with antiphosphoserine antibody, demonstrated a rapid increase (1.5- to 2-fold) in p47phox phosphorylation in Ang II-stimulated cells. This was associated with p47phox translocation from cytosol to membrane, as assessed by immunoblotting and immunofluorescence. PP2 abrogated these effects. Long-term Ang II stimulation (6 to 24 hours) increased NAD(P)H oxidase subunit expression. c-Src inhibition decreased abundance of gp91phox, p22phox, and p47phox. Confirmation of c-Src-dependent regulation of NAD(P)H oxidase was tested in VSMCs from c-Src-/- mice. Ang II-induced *O2- generation was lower in c-Src-/- than c-Src+/+ counterparts. This was associated with decreased p47phox phosphorylation, blunted Ang II-stimulated NAD(P)H oxidase activation, and failure of Ang II to increase subunit expression. CONCLUSIONS: c-Src regulates NAD(P)H oxidase-derived *O2- generation acutely by stimulating p47phox phosphorylation and translocation and chronically by increasing protein content of gp91phox, p22phox, and p47phox in Ang II-stimulated cells. These novel findings identify NAD(P)H oxidase subunits, particularly p47phox, as downstream targets of c-Src.

Angiotensin II↗

Inhibition of Th1- and enhancement of Th2-initiating cytokines and chemokines in trichosanthin- treated macrophages.

Trichosanthin (TCS), the major effective component from Chinese herb Trichosanthes Kirilowii Maxim, is also a potent allergen. Our previous work has shown that TCS can upregulate interleukin-4 (IL-4) and interleukin-13 (IL-13) while inhibit interferon-gamma (IFN-gamma) in mesenteric lymph node cells after TCS immunization. Thus, TCS can arouse a T helper 2 (Th2) response in the draining lymph node. However, little is known about the early effects of TCS on antigen-presenting cells, the initiator of T cell response. In the current study, the effects of TCS on macrophage cytokines and chemokine expression were investigated. Peritoneal macrophages were treated with or without TCS in the presence of lipopolysaccharide (LPS). We found that TCS increased macrophage interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) expression, whereas it decreased interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) expression. Our study clearly demonstrated that TCS, as an allergen, has differential effects on macrophage Th1/Th2 initiative factors, effects that are likely to facilitate its inducing of Th2 and immunoglobulin E (IgE) response.

Allergens↗

Study of microdeletions in the Y chromosome of infertile men with idiopathic oligo- or azoospermia.

PURPOSE: To determine the relationships between idiopathic oligo- or azoospermia and microdeletions of the Y chromosome. METHODS: Eighteen Y-linked sequence-tagged sites (STSs) in AZF (Azoospermia Factor) region were screened by means of multiplex PCR (Polymerase Chain Reaction) in 50 idiopathic infertile men, including 16 patients with azoospermia, 13 severe oligospermia, and 21 oligospermia. RESULTS: Microdeletions in the genomic DNA were observed in 8 of 50 cases, 3 with azoospermia, I severe oligospermia, and 4 oligospermia. Total deletion rate was 16.0% (8/50). The deletion regions were concentrated on AZFd and AZFc. CONCLUSIONS: Microdeletions of the Y chromosome are an important cause for idiopathic oligo- or azoospermia. Multiplex PCR is a useful technique for detecting the microdeletions. To avoid transmission to their offspring, patients with idiopathic oligo- or azoospermia should be screened for microdeletions of the Y chromosome before ICSI treatment for infertility.

Adult↗

Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai, China.

OBJECTIVE: Hepatitis B virus (HBV) genotype distribution is still unclear in China, where a high prevalence of HBV infection exists, although it is well known that HBV can be classified into six genotypes based on intergroup divergence. The aim of this study was to investigate the epidemiological distribution of HBV genotypes and to clarify further the genotype-related differences in the pathogenicity of HBV. METHODS: Seminested PCR and restriction fragment length polymorphism analysis were conducted in 97 asymptomatic HBV carriers (ASC) and 46 chronic hepatitis (CH), 37 liver cirrhosis (LC) and 44 hepatocellular carcinoma (HCC) patients in Shanghai, China. RESULTS: Two hundred and twenty samples (98.2%) were positive for HBV DNA, and of these, 3 (1.4%), 38 (17.2%) and 179 (81.4%) were classified as genotype A, B and C, respectively. There was a statistically significant difference in the distribution of genotypes B and C among various categories of liver diseases (p < 0.01). The distribution of genotype C showed an increasing trend from ASC, CH and LC to the HCC group; in contrast, the distribution of genotype B showed a decreasing trend in the same order. HBeAg positivity was higher in genotype C than in genotype B in all the subjects or in the ASC group alone (p < 0.05, p < 0.01, respectively). More severe liver damage and a higher mean age were observed in genotype C than in genotype B (p < 0.01, p < 0.05, respectively). CONCLUSIONS: These results indicate the following: (1) genotypes A, B and C of HBV exist in Shanghai, China; (2) genotype C is the major genotype in this area; (3) genotype C is associated with the development of severe liver diseases, and (4) genotype B has a relatively good prognosis.

Adolescent↗

[Evaluation of protective efficacy of two tuberculosis DNA vaccines by lung histopathological analysis].

OBJECTIVE: To evaluate the protective efficacy of MPT64 and ESAT6 DNA vaccines from M. tuberculosis. METHODS: BALB/c mice were randomly divided into five groups and subjected to the following treatments respectively, i.e. immunized with saline (A), plasmid vector (B), M. bovis BCG (C), MPT64 DNA vaccine (D) or ESAT6 DNA vaccine (E); and then infected by intraperitoneal injection with M. tuberculosis H37Rv. The lung histopathological changes were observed 5 or 10 weeks after infection by microscopy. RESULTS: At 5 weeks after infection, the lung lesions in the mice of group A and B had inflammatory infiltration with epithelial cell granulomas. In the mice of group C, main pathological changes were epithelial cell granulomas with moderate granulate hyperplasia in alveolar walls. The lung lesions of 3 mice in group D and 1 mice in group E were similar to those seen in the mice in group A and B. The lung lesions of 2 mice in group D and 4 mice in group E were similar to those seen in the mice in group C. At 10 weeks after infection, their tuberculous pneumonia tended to recovery. For the mice in groups A, B and D, their lung pathology exhibited tuberculous granulomas consisted of numerous macrophages, lymphocytes and a few epithelial cells with moderate granulate hyperplasia in alveolar walls. For the mice in groups of C and E, their lung developed epithelial cell and lymphocytic granulomas with moderate to severe granulate hyperplasia in alveolar walls. Lung tissue necrosis was not observed in any mouse. CONCLUSIONS: MPT64 and ESAT6 DNA vaccines from M. tuberculosis could enhance immunity against M. tuberculosis. The protective efficacy of ESAT6 DNA vaccine is stronger than that of MPT64 DNA vaccine, but not stronger than that of Mycobacterium bovis BCG.

Animals↗

Crystallization and preliminary X-ray analysis of luffaculin, a ribosome-inactivating protein from sponge-gourd seeds.

Luffaculin is a ribosome-inactivating protein. Crystals suitable for X--ray diffraction were first obtained using the hanging-drop vapour-diffusion method. X-ray studies show that the crystals belong to space group C2, with unit-cell parameters a = 89.90, b = 59.82, c = 55.18 A, beta = 120.81 degrees, and have one molecule in the crystallographic asymmetric unit. The crystals diffract X-rays to at least 2.0 A resolution.

Animals↗

The hinge of the human papillomavirus type 11 E2 protein contains major determinants for nuclear localization and nuclear matrix association.

The E2 protein of papillomaviruses is a site-specific DNA binding nuclear protein. It functions as the primary replication origin recognition protein and assists in the assembly of the preinitiation complex. It also helps regulate transcription from the native viral promoter. The E2 protein consists of an amino-terminal (N) trans-acting domain, a central hinge (H) domain, and a carboxyl-terminal (C) protein dimerization and DNA binding domain. The hinge is highly divergent among papillomaviruses, and little is known about its functions. We fused the enhanced green fluorescent protein (GFP) with the full-length human papillomavirus type 11 (HPV-11) E2 protein and showed that the resultant fusion, called gfpE2, maintained transcription and replication functions of the wild-type protein and formed similar subnuclear foci. Using a series of GFP fusion proteins, we showed that the hinge conferred strong nuclear localization, whereas the N or C domain was present in both cytoplasm and nucleus. Biochemical fractionation demonstrated that the N domain and hinge, but not the C domain, independently associated with the nuclear matrix. Mutational analyses showed that a cluster of basic amino acid residues, which is conserved among many mucosotropic papillomaviruses, was required for efficient nuclear localization and nuclear matrix association. This mutation no longer repressed the HPV-11 upstream regulatory region-controlled reporter expression. However, a very small fraction of this mutant colocalized with E1 in the nucleus, perhaps by a piggyback mechanism, and was able to support transient replication. We propose that the hinge is critical for the diverse regulatory functions of the HPV-11 E2 protein during mRNA transcription and viral DNA replication.

Animals↗

Testing Thurstonian Case V ranking models using posterior predictive checks.

This paper presents the results of a Monte Carlo study which investigates the validity of the method of posterior predictive checks (PPC) for testing the fit of a Thurstonian Case V ranking model. The PPC method is employed as an alternative to standard goodness-of-fit tests which are of limited use even when the number of items to be ranked is small. Several test quantities are formed to assess the fit of the Case V ranking model to data for various sample sizes and for two types of violations of the Case V assumptions: heterogeneous stimulus variances and rankers from different populations. The study concludes that the PPC method is useful in detecting local and global misfits of a Thurstonian Case V model, even when the ranking data are sparse.

Humans↗

[Dural arterovenous fistula involving cavernous sinus].

OBJECTIVE: To study the pathogenesis and treatment of dural arteriovenous fistulas (DAVFS) involving the cavernous sinus. METHODS: 32 cases were embolized with particle by microcatheterization via endovascular approach and ervation by digital substraction angiography. Of the 32 cases, 14 were embolized by microsoils through superior petrosal sinus approach into the cavernous sinus. RESULTS: In 28 of the 32 cases the fistulas were completely embolized angiographically. The fistulas were partly embolized in 4 of the 32 cases. The carotid artery was compressed for 6 months. One week later, the fistula disappeared angiographically. No fistulas were found during the follow-up for 6 months to 8 years. CONCLUSION: Endovascular treatment of DAVFS involving the cavernous sinus is effective.

Adolescent↗

Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways. Demonstration of competition and compensation.

The aryl hydrocarbon receptor (AHR) and the alpha-class hypoxia inducible factors (HIF1alpha, HIF2alpha, and HIF3alpha) are basic helix-loop-helix PAS (bHLH-PAS) proteins that heterodimerize with ARNT. In response to 2,3,7,8-tetrachlorodibenzo-p-dioxin, the AHR. ARNT complex binds to "dioxin responsive enhancers" (DREs) and activates genes involved in the metabolism of xenobiotics, e.g. cytochrome P4501A1 (Cyp1a1). The HIF1alpha.ARNT complex binds to "hypoxia responsive enhancers" and activates the transcription of genes that regulate adaptation to low oxygen, e.g. erythropoietin (Epo). We postulated that activation of one pathway would inhibit the other due to competition for ARNT or other limiting cellular factors. Using pathway specific reporters in transient transfection assays, we observed that DRE driven transcription was markedly inhibited by hypoxia and that hypoxia responsive enhancer driven transcription was inhibited by AHR agonists. When we attempted to support this cross-talk model using endogenous loci, we observed that activation of the hypoxia pathway inhibited Cyp1a1 up-regulation, but that activation of the AHR actually enhanced the induction of Epo by hypoxia. To explain this unexpected additivity, we examined the Epo gene and found that its promoter harbors DREs immediately upstream of its transcriptional start site. These experiments outline conditions where inhibitory and additive cross-talk occur between the hypoxia and dioxin signal transduction pathways and identify Epo as an AHR-regulated gene.

Base Sequence↗

Monte Carlo simulation of an optical coherence tomography signal in homogeneous turbid media.

The Monte Carlo technique with angle biasing is used to simulate the optical coherence tomography (OCT) signal from homogeneous turbid media. The OCT signal is divided into two categories: one is from a target imaging layer in the medium (Class I); the other is from the rest of the medium (Class II). These two classes of signal are very different in their spatial distributions, angular distributions and the numbers of experienced scattering events. Multiply scattered light contributes to the Class I signal as well as the Class II signal. The average number of scattering events increases linearly with the probing depth. The Class II signal decays much more slowly than the Class I signal whose decay constant is close to the total attenuation coefficient of the turbid medium. The effect of the optical properties of the medium on the Class I signal decay is studied.

Anisotropy↗

Full-field mapping of ultrasonic field by light-source-synchronized projection.

A simple method for imaging ultrasonic fields in clear media is introduced. A modulated laser source is used to project the ultrasonic field onto a CCD camera. By use of the source-synchronized lock-in detection scheme, 2D images of the amplitude and phase distributions can be determined simultaneously. This technique is experimentally demonstrated with a 1-MHz and a 3.5-MHz ultrasonic transducer operated in continuous-wave mode. This method is very straightforward to implement and can be combined with the traditional tomographic reconstruction technique to obtain the 3D distribution of an ultrasonic field.

Humans↗

[Long-term effect of lamivudine treatment in chronic hepatitis B virus infection].

OBJECTIVE: To evaluate the long-term effect of lamivudine on the loss of serum HBV DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance with multi-center, randomized, double blind and placebo controlled trial. METHOD: 429 patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. 322 patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks of open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: After 12 weeks treatment, HBV DNA response (serum HBV DNA < 1.6 ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P < 0.01); but at week 52, there was no difference between lamivudine and placebo/lamivudine groups (71.0% VS 77.7%, P > 0.05). Rate of HBV DNA breakthrough in lamivudine group was higher than in placebo/lamivudine group (24.4% VS 8.5%, P < 0.01). Proportion of HBeAg/anti-HBe seroconversion had no difference in two groups (7.5% VS 5.2%, P > 0.05). By week 12, ALT normalization rate in lamivudine group was higher than in placebo group (60.3% VS 27.5%, P < 0.01); but after 52 weeks treatment, there was no difference between two groups (70.9% VS 74.5%, P > 0.05). At week 48, HBV YMDD mutation rate in lamivudine group was higher than in placebo/lamivudine group (14.6% VS 5.0%, P < 0.05). The incidence of adverse events was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There was few severe drug-related adverse event. CONCLUSION: Sustained HBV replication suppression could be obtained from long-term treatment with lamivudine 100 mg daily accompanied with good tolerance and safety.

Adolescent↗

A randomized double-blind placebo-controlled study of lamivudine in the treatment of patients with chronic hepatitis B virus infection.

OBJECTIVE: To evaluate the effect of lamivudine on the loss of serum hepatitis B virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance compared with placebo. METHODS: Four hundred and twenty-nine patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty-two patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 9-month open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: During the 12-week treatment period, 92.2% of lamivudine treated patients became HBV DNA negative (below 1.6 pg/ml) compared with only 14.1% of those receiving placebo (P < 0.01). At the end of 12 week, the sustained negative rate for HBV DNA in the lamivudine treated group was 78.5% compared with the placebo group (11.1%; P < 0.01). There was a trend to a high proportion of patients treated with lamivudine to lose HBeAg (8.1%) and develop antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this difference was not statistically significant. Patients with elevated ALT levels at baseline became normal in 60. 3% of the lamivudine treated group compared with the placebo group where only 27.5% were normal (P < 0.01). Lamivudine was well tolerated in a dose of (100 mg daily) and the overall incidence of adverse events was similar to that of the placebo. CONCLUSIONS: Lamivudine (100 mg daily) is very effective in the inhibition of HBV replication, indicated by the rapid loss of serum HBV DNA, and often accompanied by a decrease of serum ALT levels. Lamivudine is well tolerated without severe adverse events during treatment.

Adolescent↗

[Morphological cure of cerebral arteriovenous malformations by endovascular therapeutics].

OBJECTIVE: To sum up the clinical characteristics and typical manifestation by analysing clinical materials from total embolized cerebral arteriovenous malformations (AVM) via endovascular embolization. METHODS: We reviewed clinical and image materials of 50 patients whose cerebral AVM were embolized entirely and found the cerebral AVM morphological cure by endovascular embolization after studying the size, position, artery supply, therapeutics and follow-up. RESULTS: 50 patients with cerebral AVM were embolized by endovascular therapy, accounting for 17% of all patients. Malformation lesions were medium or small type, with a diameter less than 3 cm, 95% of them were located in the tentorium superior. Terminal end blood supply was common to AVM and especially medium cerebral artery (MCA) or its branches. 97% of the patients were graded III or below by spectzler grading system. 70% of them had a history of intracranial hemorrhage and were cured by one therapy. CONCLUSIONS: It is a reliable and feasible method for morphological cure in cerebral AVM via endovascular therapeutics only, but case selection is important, that is, medium or small AVM with single branch terminal end blood supply in the tentorium superior.

Adolescent↗

Long-term efficacy of recombinant interferon alpha 2a in the treatment of chronic hepatitis C: a randomized prospective study comparing two dose schedules in Chinese patients.

OBJECTIVE: To compare the long-term efficacy of a dose of 3 million units (MU) of r-IFN alpha 2a (IFN-alpha 2a) three times a week (t.i.w.) for 6 months with a starting dose 6 MU for 3 months and subsequent reduction to 3 MU t.i.w for further 3 months. METHODS: Sixty-eight serological and histological chronic hepatitis C patients with elevated serum alanine aminotransferase (ALT) were enrolled and randomized into two groups. Sixty-three patients were completed with full course of treatment. Five patients were withdrawn from trial (2 due to personal reasons and 3 due to adverse drug reactions during treatment). Thirty patients received 6 MU IFN-alpha 2a t.i.w., 3 months followed by 3 MU t.i.w. for another 3 months (Group A). Thirty-three patients received 3 MU IFN-alpha 2a t.i.w. for 6 months (Group B). RESULTS: The sex, age, baseline serum bilirubin, ALT and aspartate aminotransferase (AST) levels were matched in both groups. At the end of the 6th month, the complete and partial response rates in Group A were 60.0% and 16.7% respectively, and the clearance of serum HCV-RNA was 53.3%. In Group B, the complete and partial response rates were 72.7% and 6.1% respectively, and the clearance of HCV-RNA was 61.3%. The patients were followed up for 6, 12, and 18 months after stopping treatment. In Group A, the rates of complete normalization of ALT and clearance of serum HCV-RNA at 24 months were 50.0% and 60.0% respectively. In Group B, the rates of normalization of ALT and clearance of HCV-RNA at 24 months were 54.4% and 41.9% respectively. The efficacy between the two groups showed no statistically significant difference. The response rates of treatment were similar to those in the patients with HCV genotype 1b and 2a. Six patients (10.8% of the study population) developed neutralization antibodies to IFN-alpha 2a during treatment, and four of them were responded to the treatment. Adverse drug reactions (ADR), were common, but most of them were tolerable, and the incidence of ADR was in both groups, but the severity was higher in Group A. CONCLUSIONS: IFN-alpha 2a is effective in the treatment of Chinese patients with chronic hepatitis C. The sustained response rates and adverse drug reactions among two dose schedule groups are similar.

Adolescent↗