Biomedical subjects
Publications and source records attributed to Zheng Xu.
A novel nanostructure of Ni nanotubes encapsulated in carbon nanotubes has been obtained via the pyrolysis of C2H2 on an array of Ni nanotubes in an alumina membrane support and a possible mechanism has been proposed.
A bioinformatics tool called ODS3 has been created for mapping by sequencing. The tool allows the creation of integrated genomic maps from genetic, physical mapping, and sequencing data and permits an integrated genome map to be stored, retrieved, viewed, and queried in a stand-alone capacity, in a client/server relationship with the Fungal Genome Database (FGDB), and as a web-browsing tool for the FGDB. In that ODS3 is programmed in Java, the tool promotes platform independence and supports export of integrated genome-mapping data in the extensible markup language (XML) for data interchange with other genome information systems. The tool ODS3 is used to create an initial integrated genome map of the AIDS-related fungal pathogen, Pneumocystis carinii. Contig dynamics would indicate that this physical map is approximately 50% complete with approximately 200 contigs. A total of 10 putative multigene families were found. Two of these putative families were previously characterized in P. carinii, namely the major surface glycoproteins (MSGs) and HSP70 proteins; three of these putative families (not previously characterized in P. carinii) were found to be similar to families encoding the HSP60 in Schizosaccharomyces pombe, the heat-shock psi protein in S. pombe, and the RNA synthetase family (i.e., MES1) in Saccharomyces cerevisiae. Physical mapping data are consistent with the 16S, 5.8S, and 26S rDNA genes being single copy in P. carinii. No other fungus outside this genus is known to have the rDNA genes in single copy.
Epidemic Vibrio cholerae possess the VPI (Vibrio pathogenicity island) essential virulence gene cluster. The VPI is 41.2 kb in size and encodes 29 potential proteins, several of which have no known function. We show that the VPI-encoded Orf4 is a predicted 34-kDa periplasmic protein containing a zinc metalloprotease motif. V. cholerae seventh-pandemic (El Tor) strain N16961 carrying an orf4 mutation showed no obvious difference relative to its parent in the production of cholera toxin and the toxin-coregulated pilus, motility, azocasein digestion, and colonization of infant mice. However, analysis of rabbit ileal loops revealed that the N16961 orf4 mutant is hypervirulent, causing increased serosal hemorrhage and reactogenicity compared to its parent. Histology revealed a widening of submucosa, with an increase in inflammatory cells, diffuse lymphatic vessel dilatation, edema, endothelial cell hypertrophy of blood vessels, blunting of villi, and lacteal dilatation with lymphocytes and polymorphonuclear leukocytes. The mutant could be complemented in vivo with an orf4 gene on a plasmid but not with an orf4 gene containing a site-directed mutation in the putative zinc metalloprotease motif. Although its mechanism of its action is being studied further, our results suggest that the Orf4 protein is a zinc metalloprotease that modulates the pathogenesis and reactogenicity of epidemic V. cholerae. Based on our findings, we name this VPI-encoded protein Mop (for modulation of pathogenesis).
The Vibrio pathogenicity island (VPI) in epidemic Vibrio cholerae is an essential virulence gene cluster. Like many pathogenicity islands, the VPI has at its termini a phage-like integrase gene (int), a transposase-like gene (vpiT), and phage-like attachment (att) sites, and is inserted at a tRNA-like locus (ssrA). We report that the VPI precisely excises from the chromosome and that its left and right ends join to form an extrachromosomal circular excision product (pVPI). Two-stage nested PCR analysis and DNA sequencing confirmed the int-att-vpiT junction and that the core attP of pVPI is identical to the chromosomal VPI attR site. Excision was independent of toxR and toxT. Excision was independent of recA, suggesting that it is mediated by site-specific recombination. Interestingly, while excision was detected in int and vpiT mutants, excision was abolished in a double (int vpiT) mutant and was restored by plasmids containing genes for either recombinase. Excision results in deletion of A361 in the ssrA locus, which flanks the right junction of the VPI. Since A361 encodes U70 in the critical G. U base pair in the acceptor stem of the ssrA RNA that is the determinant for aminoacylation with alanine, this deletion might have deleterious effects on ssrA function. Also, vpiT may have undergone interchromosomal translocation or may represent an independent integration event, as it was found downstream of hutA in some isolates. Our results provide new insight into the molecular biology of the VPI, and we propose that the process of excision and circularization is important in the emergence, pathogenesis, and persistence of epidemic V. cholerae.
Cellular immune responses, particularly those associated with CD3(+) CD8(+) cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defective adenovirus serotype 5 (Ad5) vector, each expressing the same codon-optimized HIV-1 gag gene for immunogenicity in rhesus monkeys. The DNA vaccines were formulated with and without one of two chemical adjuvants (aluminum phosphate and CRL1005). The Ad5-gag vector was the most effective in eliciting anti-Gag CTL. The vaccine produced both CD4(+) and CD8(+) T-cell responses, with the latter consistently being the dominant component. To determine the effect of existing antiadenovirus immunity on Ad5-gag-induced immune responses, monkeys were exposed to adenovirus subtype 5 that did not encode antigen prior to immunization with Ad5-gag. The resulting anti-Gag T-cell responses were attenuated but not abolished. Regimens that involved priming with different DNA vaccine formulations followed by boosting with the adenovirus vector were also compared. Of the formulations tested, the DNA-CRL1005 vaccine primed T-cell responses most effectively and provided the best overall immune responses after boosting with Ad5-gag. These results are suggestive of an immunization strategy for humans that are centered on use of the adenovirus vector and in which existing adenovirus immunity may be overcome by combined immunization with adjuvanted DNA and adenovirus vector boosting.
Two kinds of electroluminescent devices were fabricated by doping the rare earth complex Eu(asprin)3phen into polymer PVK: (1) ITO/PVK:RE/LiF/Al; (2) ITO/PVK:RE/PBD/LiF/Al. A great difference in the EL spectrum was found between the two kinds of devices. In device (2) the intensity of 594 nm was rather weak compared with that of 614 nm. The spectrum was consistent with the photoluminescence (PL) spectrum under the state of thin film. But in device (1), the peak emission of 594 nm was comparable to that of 614 nm. Preliminary discuss on this phenomenon was made; in device (1), the recombination region was close to the metal cathode, effect of metal cathode on the electroluminescence of the rare earth complex caused the changes of the EL emission which was quite different from the TL emission. The phenomenon was not observed in device (2) whose recombination region was far from the cathode because an electron-transport layer was inserted.
The method of recombinant PCR was employed to obtain H310D mutation in 14alpha-demethylase in Candida albicans). The expression vector pYCYPS1M harboning the mutant CYP1M gene was constructed. The mutant CYPS1 was expressed in Sacchromyces cerevisiae induced by 2% galactose. At last the MICs of yeasts to Fluconazole were determined by broth microdilution testing. Expressed protein was 15% of the total microsome proteins. The MICs of yeasts expressed the mutant CYP51 were 4-fold as that of the yeasts expressed the wild CYP51. The increase of the MICs was due to the alteration H310D in CYP51. It could be concluded that the residue of H310 was important to the function of CYPS1.
The regulation of receptor-like protein tyrosine phosphatases (RPTPs) is not well understood. Although CD45 can be negatively regulated by dimerization, how dimerization is modulated is unclear. Here we show that various isoforms of CD45 differentially homodimerize in T cells. The dimerization is modulated by the sialylation and O-glycosylation of alternatively spliced CD45 exons in the extracellular domain. Thus, the smallest isoform, CD45RO--which undergoes the least extracellular sialylation and O-glycosylation--homodimerizes with the highest efficiency, resulting in decreased signaling via the T cell receptor. Because CD45 is required for T cell activation, our findings may reveal a mechanism that contributes to the termination of the primary T cell response. Our results not only demonstrate the biological significance of alternative splicing in the immune system, but also suggest a model for regulating RPTP dimerization and function.
Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. We comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid DNA vector, the modified vaccinia Ankara (MVA) virus, and a replication incompetent adenovirus type 5 (Ad5) vector-expressing the SIV gag protein for their ability to elicit such immune responses in monkeys. The vaccines were tested either as a single modality or in combined modality regimens. Here we show that the most effective responses were elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector. After challenge with a pathogenic HIV-SIV hybrid virus (SHIV), the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the virus infection. The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine.
OBJECTIVE: To investigate the expressions of estrogen (E) receptor and progesterone (P) receptor in human eutopic and ectopic endometrium and the effect of mifepristone (RU486) on them. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Twenty-two patients with ovarian endometriosis and 13 patients with uterine leiomyoma were recruited. INTERVENTION(S): Samples of ovarian endometrioma cyst tissue and endometrium were obtained from the 22 patients. A sample of endometrium was obtained from the 13 patients. MAIN OUTCOME MEASURE(S): Expressions of E and P receptors were determined using immunocytochemical method. RESULT(S): P receptor expression in endometrial epithelial cells with endometriosis was significantly higher than that without endometriosis in the early secretory phase. Estrogen receptor and epithelial P receptor expressions in endometriotic cells were significantly lower than those of endometrial cells during the proliferative phase, similar with the latter during the early secretory phase and significantly higher during the late secretory phase. RU486 down-regulated the expressions of E and P receptors in both the eutopic and the ectopic endometrial cells, and in some cases this down-regulating effect was more apparent when the concentration of RU486 was higher. CONCLUSION(S): Different steroid receptor expressions indicate different hormonal regulation between endometriotic and endometrial cells. The down-regulating effect on E and P receptors may be one of the therapeutic mechanisms of RU486 on endometriosis.
The Akt (or protein kinase B) and Cot (or Tpl-2) serine/threonine kinases are associated with cellular transformation. These kinases have also been implicated in the induction of NF-kappa B-dependent transcription. As a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, Cot can also activate MAP kinase signaling pathways that target AP-1 and NFAT family transcription factors. Here we show that Akt and Cot physically associate and functionally cooperate. Akt appears to function upstream of Cot, as Akt can enhance Cot induction of NF-kappa B-dependent transcription, and dominant-negative Cot blocks the activation of this element by Akt. Furthermore, deletion analysis shows that binding to Akt is critical for Cot function. The regulation of NF-kappa B-dependent transcription by Cot requires Akt-dependent phosphorylation of serine 400 (S400), near the carboxy terminus of Cot. However, phosphorylation at this site is not required for Cot kinase activity or AP-1 induction, suggesting it specifically regulates Cot effector function at the level of the NF-kappa B pathway. Mutation of S400 in Cot does indeed abolish its ability to activate I kappa B-kinase (IKK) complexes, but paradoxically it allows for increased Cot association with the IKK complex. This mutated form of Cot also acts as a dominant negative for T-cell antigen receptor/CD28- or Akt/phorbol myristate acetate-induced NF-kappa B induction, while having relatively little effect on tumor necrosis factor induction of NF-kappa B. These findings suggest that the activation of different signaling pathways by MAP3Ks may be regulated separately and may provide evidence for how such discrimination by one member of this kinase family occurs.
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In this study, we characterize the function of the tumor suppressor gene PTEN in Jurkat T cells. We established stable clones of Jurkat T cells that inducibly express either wild-type or phosphatase-inactive PTEN. We show here that PTEN potently inhibited the growth and reduced the size of Jurkat cells. The growth-suppressive effect of PTEN was associated with its ability to induce apoptotic cell death with little or no effect on cell cycle. PTEN also rendered Jurkat cells more susceptible to apoptosis induced by various stimuli. Furthermore, PTEN expression led to a reduction in the level of 3'-phosphorylated phospholipids and thus altered the activity and localization of Akt. Finally, coexpression of constitutively active Akt reversed the effects caused by PTEN. In summary, our results suggest that PTEN suppresses cell growth, promotes apoptosis, and decreases cell size by negatively regulating the phosphoinositide 3-kinase/Akt pathway in Jurkat T cells.
OBJECTIVES: To establish the testicular fibrosis model in rats. METHODS: Wistar rats were divided into control group(n = 12) and model group(n = 40) randomly. Testicular fibrosis model was built with the classical method of establishing experimental autoimmune orchitis (EAO) combined with injecting Bacille Calmette-Guerin (BCG) into left testis. RESULTS: The incidence rate of EAO and the rate of testicular fibrosis were 100%, 11.1% and 100%, 81.5% at 80, 140 days after the first infection, respectively. CONCLUSIONS: The model of rat testicular fibrosis was established successfully.
Two devices structures of ITO/PVK: Rubrene/Al and ITO/Alq3:MN-PPV/Al were developed. Their characters of photoluminescence and electroluminscence were studied. The result showed that there were great difference between the photoluminescence and electroluminscence at a doping ratio of 2 wt% in ITO/PVK: Rubrene/Al. It is concluded that energy transfer in these dye-doped devices occurred by Förster energy transfer processes. And the trap effect of electrons of Rubrene on holes of PVK resulted in different combination probability of PVK excitation in photoluminescence and electroluminescence. At the same time, the two EL devices were color-tunable when the bias voltage was increased. The mechanisms which cause color variation are different. In the first device, it indicates that the energy transfer process from PVK to Rubrene is not complete. The combination probability of PVK excitation which does not contribute to the emission of Rubrene is increased when the bias voltage increases. But in the second device, there are many micro-interfaces due to the phase-separation just like the interface in a double layer device. The tunneling interface barriers of carriers is the main cause of color variation in the second device.
Semiconductor nanocrystals appear different optical properties from their bulk analogous due to quantum confinement effects. It is well known that optical absorption of nanocrystals shift to higher energy as the sizes decrease, while the emission at the absorption band edge is always too weak to be investigated in details due to much nonradiative recombination at nanoparticle surface. To eliminate the surface defects, some kinds of materials such as organic molecules, polymers and inorganic compounds are used to overcoat the nanoparticles. It has been found that nanocrystals overcoated with high band gap inorganic materials maned core/shell type nanocrystals exhibit high photoluminescence intensity at band edge due to effective elimination of surface nonradiative recombination. In this article we report the characteristics of CdSe/CdS core/shell nanocrystals synthesized with mercapto acid as stabilizer. The effect of CdS shell on the electronic characteristics and the luminescence of CdSe core were investigated by using optical absorption, photoluminescence and photoluminescence excitation spectra. Large band edge luminescence enhancement was found in CdSe nanoparticles overcoated with the CdS shell with a thickness of 0.3 nm due to passivation of nonradiative recombination sites on CdSe surfaces. Such bandadge emission also appeared redshift from the absorption maximum. This Stokes shift of the emission peak from the absorption edge was explained by a model of formation of excimer among the small nanoparticles based on the optical experimental results and the theoretical calculation on fine structures of bandadge excitons.
Regulation of tyrosine phosphorylation is a critical control point for integration of environmental signals into cellular responses. This regulation is mediated by the reciprocal actions of protein tyrosine kinases and phosphatases. CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expressed on all nucleated hematopoietic cells and plays a central role in this process. Studies of CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient humans initially demonstrated the essential role of CD45 in antigen receptor signal transduction and lymphocyte development. It is now known that CD45 also modulates signals emanating from integrin and cytokine receptors. Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity. From these studies, a model is emerging in which CD45 affects cellular responses by controlling the relative threshold of sensitivity to external stimuli. Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states.
To observe therapeutic effects of Lishengsu (recombinant human granulocyte colony stimulating factor, rhG-CSF) on leukopenia induced by chemotherapy, 40 patients with malignant tumor included in the clinical observation were randomly divided into group A and B (20 patients each). Each patient was received two cycles of chemotherapy. In group A Lishengsu was administered in the first cycle and none in the second cycle, while in group B Lishengsu was given in the second cycle, but not in the first cycle. Lishengsu was subcutaneoasly injected for 5 - 7 days at dosage of 75 micro g or 150 micro g per day 24 - 48 hours after completion of chemotherapy. The results showed that Lishengsu remarkably alleviated the degree of leukopenia and neutropenia, and lower the incidence of infection. The curative effect of Lishengsu is reliable with slight side-effects, and it might assist to completion of chemotherapy in tumor patiants.