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Biomedical subjects

X Zhang

Publications and source records attributed to X Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2005

Cyclosporine inhibits the development of green fluorescent protein (GFP)-specific immune responses after transplantation of GFP-expressing hematopoietic repopulating cells in dogs.

Green fluorescent proteins (GFPs) have been widely used to monitor gene transfer and expression after lentiviral and oncoretroviral transduction of hematopoietic cells. Studies have shown a complete disappearance of GFP-containing cells after transplantation of GFP-transduced repopulating cells in nonhuman primates that was further shown to be mediated by transgene-specific immune responses. We wished to evaluate whether cyclosporine could prevent immune responses to GFP. We first determined whether an immune response to GFP was responsible for the disappearance of gene-modified cells in dogs. We performed immune assays in two dogs transplanted with lentivirally transduced CD34+ cells. Blood samples were obtained twice per week for up to 800 days and the GFP transgene product was measured by flow cytometry in blood leukocytes. Peripheral blood leukocytes were stimulated in vitro for 5 days, using a panel of GFP peptides. Intracellular levels of tumor necrosis factor alpha (TNF-alpha), measured by flow cytometry, and T cell proliferation after GFP peptide stimulation were measured. Dogs that exhibited a decrease in GFP marking developed potent immune responses in vitro to the transgene product GFP as shown by an increase in GFP-specific TNF-alpha production (p < 0.05) when compared with nontransplanted controls. T cells from dogs with low GFP marking exhibited a significant increase in proliferation in response to GFP peptide stimulation in vitro (p < 0.05). To study whether cyclosporine could inhibit the development of GFP-specific immune responses, we treated five dogs with cyclosporine after transplantation of GFP-transduced hematopoietic cells. Dogs treated with cyclosporine after hematopoietic stem cell transplantation showed stable GFP marking in blood leukocytes over 800 days. Our data suggest that cyclosporine prevents immunoactivation against transgene products after transplantation of GFP-transduced hematopoietic stem cells as indicated by stable GFP marking.

Animals↗
PubMed2005

Acute stress reduces intraparenchymal lung natural killer cells via beta-adrenergic stimulation.

There are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home-cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed2005

Enhanced maturation and functional capacity of dendritic cells induced by mannosylated L2 domain of ErbB2 receptor.

The nature of antigens and functional state of dendritic cells (DC) are important in antigen presentation. The ability of DC for the induction of T-cell responses is promoted by maturation. It has been confirmed that mannose receptors mediate highly efficient endocytosis and presentation of mannosylated proteins. In the present study, L2 domain of ErbB2 ectodomain was expressed in Escherichia coli, purified and mannosylated. The maturation and functional capacity of DC induced by mannosylated L2 (mL2) protein were investigated. The results showed that L2 protein could induce DC maturation, which was accompanied by elevated expression of MHC and co-stimulatory molecules. The effect of mL2 protein on DC maturation was more remarkable than that of non-mL2 proteins. Uptake of mL2 antigens by DC was more efficient. Furthermore, the T cells can be stimulated to proliferate in vitro and secrete Th1 and Th2 cytokines. Higher levels of both IFN-gamma and IL-10 were detected from the T cells stimulated by mL2-pulsed DC, suggesting a concurrent activation of CD4+ and CD8+ T cells. The results demonstrated that L2 domain of ErbB2 receptor is an immunodominant molecule. The mL2 domain of ErbB2 can induce an enhanced maturation and functional capacity of DC. It may become an effective strategy to induce anti-ErbB2 response.

Antigen Presentation↗
PubMed2005

A novel blocking monoclonal antibody recognizing a distinct epitope of human CD40 molecule.

CD40, a member of the tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Here, we report a blocking mouse antihuman CD40 monoclonal antibody, mAb 3G3, of which the specificity was verified by flow cytometry and Western blot. It was shown by competition test that 3G3 bound to a different site (epitope) of CD40 from the reported CD40 mAbs, including clone mAb89, 3B2, and 5C11. It was also found that mAb 3G3 could inhibit homotypic aggregation of Daudi cells induced by the agonistic anti-CD40 mAb 5C11. Furthermore, mAb 3G3 effectively inhibited the proliferation of peripheral blood mononuclear cells in mixed lymphocyte reaction assay. Finally, a sensitive and specific soluble CD40 (sCD40) ELISA kit was established by matching mAb 3G3 with 5C11, and it was found that the levels of sCD40 in sera from patients with immune disorders such as hyperthyroidism, chronic nephritis, and rheumatoid arthritis were obviously higher than those from normal individuals. Thus, this blocking anti-CD40 mAb provides a novel tool for the study of CD40.

Antibodies, Monoclonal↗
PubMed2005

Identification of a novel HLA-A allele HLA-A*2451 in a Chinese donor.

A novel human leucocyte antigen-A (HLA-A) allele, A*2451, has been identified during routine sequence-specific oligonucleotide typing and sequence-based typing of a sample from a registered donor of the Chinese Marrow Donor Program. The A*2451 allele differs from the closest matching allele A*2415 by one nucleotide substitution in exon 3, nt 363 G-->A, resulting in an amino acid change from M ATG to I ATA at codon 121.

Alleles↗
PubMed2005

Neoadjuvant chemoradiotherapy for esophageal carcinoma.

SUMMARY. Neoadjuvant chemoradiotherapy is often administered to patients with esophageal carcinoma in the belief that this will improve survival. However, its role in the management of esophageal carcinoma remains controversial. In this study we evaluated our experience with neoadjuvant chemoradiotherapy for the treatment of esophageal carcinoma. The study group was 115 patients who underwent esophagectomies between January 1999 and January 2004. Eighty-nine patients had adenocarcinoma and 26 had squamous cell carcinoma. Fifty-six patients underwent neoadjuvant chemoradiotherapy (two cycles of cisplatin and 5-fluorouracil with 45 Gy radiation) followed by esophagectomy. The other 59 patients proceeded directly to esophagectomy. Outcomes were determined prospectively, and follow-up was available for all patients. Neoadjuvant chemoradiotherapy achieved down-staging of the esophageal cancer in 43%, 43% and 46% of patients, according to T, N and TNM classifications, respectively. Neoadjuvant chemoradiotherapy resulted in a complete pathological response in seven (13%) patients. The surgical morbidity rate was 37% (42/115), and in-hospital mortality was 5% (6/115). There were no differences between patients who did and did not undergo neoadjuvant chemoradiotherapy in regard to completeness of resection, perioperative mortality and postoperative morbidity. Four-year survival was 33% following neoadjuvant chemoradiotherapy, compared with 19% for patients undergoing surgery alone. The administration of neoadjuvant chemoradiotherapy in patients with esophageal carcinoma down-staged nearly 50% of tumors, and a complete pathological response occurred in some of these patients. It was not associated with any increase in postoperative morbidity or perioperative mortality. In this non-randomized study, it was also associated with a trend towards a better survival outcome.

Adenocarcinoma↗
PubMed2005

The effectiveness of family interventions in people with diabetes mellitus: a systematic review.

AIMS: To conduct a systematic review of reports of published literature to assess which family interventions are effective in improving diabetes-related outcomes in people with diabetes and family members (blood or non-blood relatives) residing in their homes. METHODS: We searched computerized bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, WOS, ERIC, Cochrane, CDP, and SocAbs) for randomized clinical trials published in any language that evaluated the effectiveness of family-based interventions with no age restriction. Only studies focused on interventions in young populations (< 18 years) and involving a parent were combined in a meta-analysis for glycated haemoglobin (GHb) using DerSimonian and Laird random effects model. Effect sizes for knowledge outcomes were estimated using the Cohen's d (standardized mean differences) formula. RESULTS: Our searches identified 19 randomized controlled trials. Positive effect sizes of family interventions on knowledge for five studies (N = 217) were demonstrated {0.94 [95% confidence interval (CI) 0.67, 1.82]}. A beneficial effect of interventions on GHb for eight studies (N = 505) was also observed using meta-analysis [-0.6 (95% CI -1.2, -0.1)]. CONCLUSIONS: Evidence suggests that family interventions in family or household members of people with diabetes may be effective in improving diabetes-related knowledge and glycaemic control.

Adult↗
PubMed2005

G309D and W437OPA PINK1 mutations in Caucasian Parkinson's disease patients.

OBJECTIVE: To determine whether the G309D and W437OPA mutations in PINK1 gene are present in American Caucasian population of patients with Parkinson's disease (PD). METHODS: We searched for the G309D and W437OPA mutation by sequencing the regions of interest in the PINK1 gene in 237 unrelated Caucasian patients. RESULTS: None of the 237 samples showed the G309D or W437OPA mutations. CONCLUSIONS: The G309D and W437OPA mutations in PINK1 gene probably do not represent common causes of familial or sporadic PD in a Caucasian population.

Adult↗
PubMed2005

Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring.

BACKGROUND AND AIMS: Acid gastro-oesophageal reflux is one of the most important causes of chronic cough. The response to acid suppression in these patients is not as good as in patients with heartburn but improvement with antireflux surgery has been reported, suggesting the involvement of a non-acidic gastric component in the refluxate. Less acidic reflux may produce symptoms such as regurgitation or chest pain. We investigated whether chronic cough might be associated with weakly acidic reflux. METHODS: We studied 28 patients with chronic cough using 24 hour ambulatory pressure-pH-impedance monitoring. Manometry was used for precise recognition of cough and impedance-pHmetry to detect acid (pH <4), weakly acidic (pH 7-4), and weakly alkaline (impedance drops, pH >/=7) reflux. A symptom association probability (SAP) analysis was performed for each type of reflux. RESULTS: Analysis was completed in 22 patients with 24 cough events (5-92)/patient. The majority of cough events (69.4%) were considered "independent" of reflux whereas 30.6% occurred within two minutes of a reflux episode. Half of these (49%) were "reflux cough" sequences, involving acid (65%), weakly acidic (29%), and weakly alkaline (6%) reflux. Ten patients (45%) had a positive SAP between reflux and cough: five with acid, two with acid and weakly acidic, and three only with weakly acidic reflux. CONCLUSIONS: Ambulatory pressure-pH-impedance monitoring with SAP analysis allowed precise determination of the temporal association between cough and gastro-oesophageal reflux (acid, weakly acidic, and weakly alkaline) and identification of a subgroup of patients with chronic cough clearly associated with weakly acidic gastro-oesophageal reflux.

Adult↗
PubMed2005

Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer.

BACKGROUND: The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (-1377G-->A) and FASL (-844T-->C) and risk of oesophageal cancer. OBJECTIVE: To examine the contribution of these polymorphisms to risk of developing lung cancer. METHODS: Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. RESULTS: Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS -1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL -844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS -1377AA and FASL -844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. CONCLUSION: These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

Aged↗
PubMed2005

The simple ultrastructure of the maize kinetochore fits a two-domain model.

Light microscope observations suggest there are two discrete biochemical domains in the plant kinetochore, an inner domain containing structural proteins, and an outer domain containing proteins involved in motility. We analyzed the ultrastructure of maize meiotic kinetochores following high pressure freezing and freeze substitution, a method that provides excellent sample preservation. Data from meiosis II support previous descriptions of plant kinetochores as diffuse, nearly invisible domains, sometimes nesting in a cup of darkly staining chromatin. The ultrastructure is similar in meiosis I but there are two sister kinetochores that each protrude away from the chromosome and form their own distinct kinetochore fibers. Microtubules terminate within kinetochores where their ends are splayed in a cone-shaped configuration suggestive of microtubule disassembly. We could not detect any significant substructure within the kinetochore proper. We suggest that the diffuse structure classically defined as the kinetochore represents only the outer domain of a two-domain organelle. The inner domain, known to contain chromatin-binding proteins, probably extends into the electron-dense chromatin of the primary constriction.

Chromosomes, Plant↗
PubMed2005

Polymorphic karyotypes and sex chromosomes in the tufted deer (Elaphodus cephalophus): cytogenetic studies and analyses of sex chromosome-linked genes.

Different diploid chromosome numbers have been reported for the tufted deer Elaphodus cephalophus (female, 2n = 46/47; male, 2n = 47/48) in earlier reports. In the present study, chromosomal analysis of seven tufted deer (5 male symbol, 2 female symbol) revealed that the karyotype of these animals contains 48 chromosomes, including a pair of large heteromorphic chromosomes in the male. C-banding revealed these chromosomes to be very rich in constitutive heterochromatin. Chromosome banding and PCR of sex chromosome-linked genes (SRY, ZFX, ZFY) performed on DOP-PCR products of single microdissected X and Y chromosomes confirmed that the large telocentric chromosome without secondary constriction is the X chromosome whereas the subtelocentric chromosome is the Y. The increased size of both, the X and Y chromosome, appears to be at least partially attributable to the presence of substantial amounts of heterochromatin.

Animals↗
PubMed2005

Oligomeric structure of nitrilases: effect of mutating interfacial residues on activity.

Nitrilases are important industrial enzymes that convert nitriles into their corresponding acids or, occasionally, amides. Atomic resolution structures of four members of the nitrilase superfamily have been determined, but these differ from microbial nitrilases in that they do not form typical large homo-oligomeric complexes. At least two nitrilases, the cyanide dihydratases from Pseudomonas stutzeri AK61 and Bacillus pumilus C1, form unusual spiral structures of 14 and 18 subunits, respectively. Evidence suggests that the formation of the spiral structure is essential for activity. Sequence analysis reveals that the nitrilases differ from the nonspiral-forming homologs by two insertions of between 12 and 14 amino acids and a C-terminal extension of up to 35 amino acids. The insertions are positioned at an intermolecular interface in the spiral and probably contribute to its formation. The other interfaces responsible for the formation and/or stabilization of the spirals can also be identified. Comparative structure modeling enables identification of the residues involved in these interacting surfaces, which are remote from the active site. Mutation of these interacting residues usually leads to loss of activity. The effect of the mutations on activity in most cases can be rationalized in terms of a possible effect on spiral formation.

Amino Acid Sequence↗
PubMed2005

betaA- and betaC-activin, follistatin, activin receptor mRNA and betaC-activin peptide expression during rat liver regeneration.

The mRNA expression of two activin growth factor subunits (betaA- and betaC-activin), activin receptor subunits (ActRIIA, ActRIIB) and the activin-binding protein follistatin, and peptide expression of betaA-activin and betaC-activin subunits, were examined in regenerating rat liver after partial hepatectomy (PHx). Liver samples were collected from adult, male Sprague-Dawley rats, 12-240 h (n=3-5 rats per time point) after PHx or from sham-operated controls at the same time points. Hepatocyte mitosis and apoptosis were assessed histologically and by in situ cell death detection. RT and PCR were used to assess relative gene expression. betaA- and betaC-activin peptide immunoreactivity was assessed in liver and serum samples by western blotting, whereas cellular expression was investigated by immunohistochemistry, using specific monoclonal antibodies. betaA- and betaC-activin mRNA dropped to < 50% of sham control values 12 h after PHx and remained at this level until 168 h post-PHx, when betaA-activin expression increased to three times sham control values and betaC-activin mRNA returned to pre-PHx levels. A peak in follistatin expression was observed 24-48 h post-PHx, coincident with an increase in hepatocyte mitosis. No changes were observed in ActRIIA mRNA, whereas ActRIIB expression paralleled that of betaA-activin mRNA. betaC-activin immunoreactive homo- and heterodimers were observed in regenerating liver and serum. Mitotic hepatocytes frequently contained betaC-activin immunoreactivity, whereas apoptotic hepatocytes were often immunoreactive for betaA-activin. We conclude that betaA- and betaC-activin subunit proteins are autocrine growth regulators in regenerating liver and when expressed independently lead to hepatocyte apoptosis or mitosis in a subset of hepatocytes.

Activin Receptors↗
PubMed2005

Inhibition of hepatitis B virus replication by recombinant small interfering RNAs.

RNA interference (RNAi) is a biological phenomenon in which introduction of a small, double-stranded interfering RNAs (siRNAs) into a cell causes a specific degradation of homologous single-stranded RNA. siRNA can be delivered into the cell by different approaches including synthetic RNA, in vitro transcribed RNA and RNA transcribed from polymerase III-based recombinant vectors. As hepatitis B (HB) represents a worldwide health problem, we attempted to develop a fast and easy approach to generation and screening of specific siRNA-targeted HB virus (HBV) genes. Using PCR amplification, specific siRNA expression cassettes (SECs) were developed and used to generate effective siRNAs against HB virus (HBV) replication and gene expression in mammalian cells. After screening, we identified two SECs that expressed siRNAs which efficiently decreased the level of HBV pre-c/c gene expression in transfected Bel-7402 cells by 81.9% and 87.3%, respectively. In addition, the level of HBV DNA was decreased by 83.5% and 85.2% in HepG2 2.2.15 cells, respectively. This study provides (i) a new effective application of RNA interference to study viral gene function and viral replication and (ii) a new tool for the prevention and treatment of human HBV infection.

DNA, Viral↗