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Li Xie

Publications and source records attributed to Li Xie.

32 records · Page 2Linked to original sources
PubMed2005

Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus.

Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia. We found that HTLV-2 Tax2 protein stimulated reporter gene expression regulated by the interleukin (IL)-2 promoter through the nuclear factor of activated T cells (NFAT) in a human T-cell line (Jurkat). However, the activity of HTLV-1 Tax1 was minimal in this system. T-cell lines immortalized by HTLV-2 but not HTLV-1 constitutively exhibited activated NFAT in the nucleus and constitutively expressed IL-2 mRNA. Cyclosporine A, an inhibitor of NFAT activation, abrogated the induction of IL-2 mRNA in HTLV-2-immortalized T-cell lines and concomitantly inhibited cell growth. This growth inhibition was rescued by the addition of IL-2 to the culture. Furthermore, anti-IL-2 receptor antibodies significantly reduced the proliferation of HTLV-2-infected T-cell lines but not that of HTLV-1-infected cells. Our results suggest that Tax2 activates an IL-2 autocrine loop mediated through NFAT that supports the growth of HTLV-2-infected cells under low-IL-2 conditions. This mechanism would be especially important in vivo, where this autocrine mechanism establishes a nonleukemogenic life-long HTLV-2 infection. The results also suggest that differences in long-term cytokine production between HTLV-1 and HTLV-2 infection are another factor for the differences in pathogenesis.

Base Sequence↗
PubMed2005

Envelope is a major viral determinant of the distinct in vitro cellular transformation tropism of human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2.

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are related deltaretroviruses but are distinct in their disease-inducing capacity. These viruses can infect a variety of cell types, but only T lymphocytes become transformed, which is defined in vitro as showing indefinite interleukin-2-independent growth. Studies have indicated that HTLV-1 has a preferential tropism for CD4+ T cells in vivo and is associated with the development of leukemia and neurological disease. Conversely, the in vivo T-cell tropism of HTLV-2 is less clear, although it appears that CD8+ T cells preferentially harbor the provirus, with only a few cases of disease association. The difference in T-cell transformation tropism has been confirmed in vitro as shown by the preferential transformation of CD4+ T cells by HTLV-1 versus the transformation of CD8+ T cells by HTLV-2. Our previous studies showed that Tax and overlapping Rex do not confer the distinct T-cell transformation tropisms between HTLV-1 and HTLV-2. Therefore, for this study HTLV-1 and HTLV-2 recombinants were generated to assess the contribution of LTR and env sequences in T-cell transformation tropism. Both sets of proviral recombinants expressed p19 Gag following transfection into cells. Furthermore, recombinant viruses were replication competent and had the capacity to transform T lymphocytes. Our data showed that exchange of the env gene resulted in altered T-cell transformation tropism compared to wild-type virus, while exchange of long terminal repeat sequences had no significant effect. HTLV-2/Env1 preferentially transformed CD4+ T cells similarly to wild-type HTLV-1 (wtHTLV-1), whereas HTLV-1/Env2 had a transformation tropism similar to that of wtHTLV-2 (CD8+ T cells). These results indicate that env is a major viral determinant for HTLV T-cell transformation tropism in vitro and provides strong evidence implicating its contribution to the distinct pathogenesis resulting from HTLV-1 versus HTLV-2 infections.

CD4-Positive T-Lymphocytes↗
PubMed2005

The effects of teriparatide on the incidence of back pain in postmenopausal women with osteoporosis.

OBJECTIVES: Back pain is a major cause of suffering, disability, and cost. The risk of developing back pain was assessed following treatment with teriparatide [rh(PTH 1-34)] in postmenopausal women with osteoporosis. RESEARCH DESIGN AND METHODS: A secondary analysis of back pain findings from the global, multi-site Fracture Prevention Trial was conducted where postmenopausal women with prevalent vertebral fractures were administered teriparatide 20 microg (n = 541) or placebo (n = 544) for a median of 19 months. Treatment-emergent back pain data were collected during adverse event monitoring, and spine radiographs were obtained at baseline and study endpoint. MAIN OUTCOME MEASURES: The risk of back pain stratified by severity of new or worsening back pain and the risk of back pain associated with both number and severity of new vertebral fractures. RESULTS: Women randomized to teriparatide 20 microg had a 31% reduced relative risk of moderate or severe back pain (16.5% vs. 11.5%, P = 0.016) and a 57% reduced risk of severe back pain (5.2% vs. 2.2%, P = 0.011). Compared with placebo, teriparatide-treated patients experienced reduced relative risk of developing back pain associated with findings of: one or more new vertebral fractures by 83% (6.5% vs. 1.1%, P < 0.001), two or more new vertebral fractures by 91% (2.5% vs. 0.20%, P = 0.004), and one or more new moderate or severe vertebral fractures by 100% (5.1% vs. 0.0%, P < 0.001). CONCLUSIONS: Teriparatide-treated women had reduced risk for moderate or severe back pain, severe back pain, and back pain associated with vertebral fractures. The mechanism of the back pain reduction likely includes the reduction both in severity and number of new vertebral fractures.

Back Pain↗
PubMed2005

[The in-vitro interferon-gamma release assay for the diagnosis of tuberculosis and Mycobacterium tuberculosis infections].

OBJECTIVE: To investigate the in-vitro interferon-gamma (IFN-gamma) release assay based on three different Mycobacterium tuberculosis antigens in the diagnosis of tuberculosis and Mycobacterium tuberculosis infections. METHODS: The peripheral blood mononuclear cells (PBMC) were collected from the patients with tuberculosis (tuberculosis group, n = 57), patients with lung cancer (lung cancer group, n = 29), and healthy controls (healthy control group 2, n = 27). The PBMCs were co-cultured for 5 days with different antigens: purified protein derivatives (PPD) of tuberculin, early secretary antigenic target 6,000 protein (ESAT6) and 38,000 antigen. The protein levels of IFN-gamma were detected by ELISA, and the results were compared to those with the tuberculin skin test (TST). RESULTS: (1) For healthy controls, the TST was positively related to the history of BCG vaccination and the closeness of contact with sputum-positive tuberculosis patients (P = 0.047, P = 0.041 respectively). The ESAT6 based IFN-gamma release assay was only significantly related to the closeness of contact with sputum-positive tuberculosis patients (P = 0.005), but not to the history of BCG vaccination. (2) There was no significant difference of the TST results among the three groups (P > 0.05). (3) The receiver operating characteristic (ROC) curve analysis indicated that the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the IFN-gamma release assay based on 38,000 antigen were 64.9%, 89.3%, 77.0%, 86.0%, and 71.0% respectively for the diagnosis of tuberculosis. CONCLUSIONS: IFN-gamma release assay based on ESAT6 appears to be better than TST in the diagnosis of infection of Mycobacterium tuberculosis, while IFN-gamma release assay based on 38,000 may be helpful for the diagnosis of tuberculosis.

Adult↗
PubMed2004

GIP1-39, a novel insulinotropic peptide form and aspects on its mechanism of action.

GIP1-39, a novel chain-length form of GIP (gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide), has been purified recently from porcine intestine and found to exist abundantly in this tissue. We have characterized that GIP1-39 is an insulinotropic peptide, and demonstrated that GIP1-39 is more potent in stimulating insulin secretion from rat pancreatic islets than GIP1-42, the insulinotropic polypeptide reported originally. Therefore, we have further investigated some aspects on the mechanism behind the insulinotropic effect of GIP1-39 in single rat pancreatic beta cells. GIP1-39 at 100 nM was able to significantly increase intracellular Ca2+ concentration ([Ca2+]i), and capable of enhancing exocytosis assessed by membrane capacitance measurement. The novel GIP1-39 might be a more optimal molecular pattern in stimulating insulin secretion and deserves to be further investigated biologically and clinically.

Amino Acid Sequence↗
PubMed2004

Adapting the nudged elastic band method for determining minimum-energy paths of chemical reactions in enzymes.

Optimization of reaction paths for enzymatic systems is a challenging problem because such systems have a very large number of degrees of freedom and many of these degrees are flexible. To meet this challenge, an efficient, robust and general approach is presented based on the well-known nudged elastic band reaction path optimization method with the following extensions: (1) soft spectator degrees of freedom are excluded from path definitions by using only inter-atomic distances corresponding to forming/breaking bonds in a reaction; (2) a general transformation of the distances is defined to treat multistep reactions without knowing the partitioning of steps in advance; (3) a multistage strategy, in which path optimizations are carried out for reference systems with gradually decreasing rigidity, is developed to maximize the opportunity of obtaining continuously changing environments along the path. We demonstrate the applicability of the approach using the acylation reaction of type A beta-lactamase as an example. The reaction mechanism investigated involves four elementary reaction steps, eight forming/breaking bonds. We obtained a continuous minimum energy path without any assumption on reaction coordinates, or on the possible sequence or the concertedness of chemical events. We expect our approach to have general applicability in the modeling of enzymatic reactions with quantum mechanical/molecular mechanical models.

Algorithms↗
PubMed2004

Differential gene expression in human hepatocellular carcinoma Hep3B cells induced by apoptosis-related gene BNIPL-2.

AIM: Bcl-2/adenovirus E1B 19 ku interacting protein 2-like (BNIPL-2) is a novel protein recently identified in our laboratory. BNIPL-2 is homologous to human BNIP-2, a potentially proapoptotic protein, and can interact with Bcl-2 and Cdc42GAP and promote apoptosis in BEL-7402 cells. Here we report the gene-expression profile regulated by BNIPL-2 in human hepatocarcinoma Hep3B cells and the analysis of its potential roles in cell apoptosis. METHODS: BNIPL-2 was overexpressed in Hep3B cells using tetracycline inducible or Tet-on system. Screened by Western blot, the cells with low background and high induction fold of BNIPL-2 were obtained. We performed Atlas human cDNA expression array hybridization on these cells and analyzed the data with Quantarray software to identify BNIPL-2-regulated genes and their expression profile. RT-PCR was used to confirm the altered expression level of part of genes identified by the Atlas array hybridization. RESULTS: Fifteen of 588 genes spotted on the Atlas membrane showed altered expression levels in BNIPL-2-transfected Hep3B-Tet-on cells, in which 8 genes involved in cell apoptosis or growth inhibition were up-regulated and 7 genes involved in cellular proliferation were down-regulated following overexpression of BNIPL-2. CONCLUSION: cDNA array is a powerful tool to explore gene expression profiles under inducible conditions. The data obtained using the cDNA expression microarray technology indicates that BNIPL-2 may play its roles in apoptosis through regulating the expression of genes associated with cell apoptosis, growth inhibition and cell proliferation.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Transformation studies with a human T-cell leukemia virus type 1 molecular clone.

In in vitro studies human T-cell leukemia virus type 1 (HTLV-1) may be produced by stable or transient transfection of target cells with an infectious molecular clone. Studies using primary human T cells, the natural targets of HTLV-1 infection, are hampered by difficulty in achieving significant infection with cell-free virus and a poor efficiency of transfection of primary cells. A method is described for the generation of stable cell lines expressing HTLV-1 from an infectious proviral clone. The stably transfected cells can be irradiated and cocultured with human peripheral blood mononuclear cells (PBMC) resulting in infected primary cells. These cells become immortalized, IL-2 dependent lines, which contain integrated copies of provirus and express a full spectrum of viral proteins. Analysis of cellular markers indicates that immortalized cell lines consist of CD3+/CD4+ T cells, matching the most common adult T-cell leukemia (ATL) cell phenotype. The method described has great utility in the study of the replication and transformation capacity of HTLV and HTLV mutant viruses in their natural targets, primary human T lymphocytes.

Base Sequence↗
PubMed2003

Tax and overlapping rex sequences do not confer the distinct transformation tropisms of human T-cell leukemia virus types 1 and 2.

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are distinct oncogenic retroviruses that infect several cell types but display their biological and pathogenic activity only in T cells. Previous studies have indicated that in vivo HTLV-1 has a preferential tropism for CD4+ T cells, whereas HTLV-2 in vivo tropism is less clear but appears to favor CD8+ T cells. Both CD4+ and CD8+ T cells are susceptible to HTLV-1 and HTLV-2 infection in vitro, and HTLV-1 has a preferential immortalization and transformation tropism of CD4+ T cells, whereas HTLV-2 immortalizes and transforms primarily CD8+ T cells. The molecular mechanism that determines this tropism of HTLV-1 and HTLV-2 has not been determined. HTLV-1 and HTLV-2 carry the tax and rex transregulatory genes in separate but partially overlapping reading frames. Since Tax has been shown to be critical for cellular transformation in vitro and interacts with numerous cellular processes, we hypothesized that the viral determinant of transformation tropism is encoded by tax. Using molecular clones of HTLV-1 (Ach) and HTLV-2 (pH6neo), we constructed recombinants in which tax and overlapping rex genes of the two viruses were exchanged. p19 Gag expression from proviral clones transfected into 293T cells indicated that both recombinants contained functional Tax and Rex but with significantly altered activity compared to the wild-type clones. Stable transfectants expressing recombinant viruses were established, irradiated, and cocultured with peripheral blood mononuclear cells. Both recombinants were competent to transform T lymphocytes with an efficiency similar to that of the parental viruses. Flow cytometry analysis indicated that HTLV-1 and HTLV-1/TR2 had a preferential tropism for CD4+ T cells and that HTLV-2 and HTLV-2/TR1 had a preferential tropism for CD8(+) T cells. Our results indicate that tax/rex in different genetic backgrounds display altered functional activity but ultimately do not contribute to the different in vitro transformation tropisms. This first study with recombinants between HTLV-1 and HTLV-2 is the initial step in elucidating the different pathobiologies of HTLV-1 and HTLV-2.

CD4-Positive T-Lymphocytes↗
PubMed2003

[Nitric oxide production and expression of cytokines by macrophages infected by M. tuberculosis H(37)R(v)].

OBJECTIVE: To study nitric oxide (NO) production and cytokine expression by macrophages infected by M. tuberculosis H(37)R(v), and to compare the difference between dead and live M. tuberculosis in the induction of immune responses, and thus to show if dead bacteria could be a possible candidate for new vaccines. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and ELISA were used to measure the production of NO and cytokines in macrophages infected by H(37)R(v). RESULTS: Macrophages infected by viable M. tuberculosis produced more NO, IL-1, IL-12, IL-18, TNF-alpha and inducible nitric oxide synthases (iNOS), as compared with macrophages infected by dead bacteria. The number of bacteria was also an important factor determining the production of NO and cytokines. CONCLUSIONS: Viable M. tuberculosis H(37)R(v) can induce the activation of macrophages and the production of more NO and cytokines which play important roles in the host immune response. Heat-killed M. tuberculosis H(37)R(v) failed to induce activation of macrophages and the production of NO and cytokines, which makes it unlikely to be a candidate for vaccine development.

Cells, Cultured↗
PubMed2002

The treatment of solvation by a generalized Born model and a self-consistent charge-density functional theory-based tight-binding method.

We present a model to calculate the free energies of solvation of small organic compounds as well as large biomolecules. This model is based on a generalized Born (GB) model and a self-consistent charge-density functional theory-based tight-binding (SCC-DFTB) method with the nonelectrostatic contributions to the free energy of solvation modeled in terms of solvent-accessible surface areas (SA). The parametrization of the SCC-DFTB/GBSA model has been based on 60 neutral and six ionic molecules composed of H, C, N, O, and S, and spanning a wide range of chemical groups. Effective atomic radii as parameters have been obtained through Monte Carlo Simulated Annealing optimization in the parameter space to minimize the differences between the calculated and experimental free energies of solvation. The standard error in the free energies of solvation calculated by the final model is 1.11 kcal mol(-1). We also calculated the free energies of solvation for these molecules using a conductor-like screening model (COSMO) in combination with different levels of theory (AM1, SCC-DFTB, and B3LYP/6-31G*) and compared the results with SCC-DFTB/GBSA. To assess the efficiency of our model for large biomolecules, we calculated the free energy of solvation for a HIV protease-inhibitor complex containing 3,204 atoms using the SCC-DFTB/GBSA and the SCC-DFTB/COSMO models, separately. The computed relative free energies of solvation are comparable, while the SCC-DFTB/GBSA model is three to four times more efficient, in terms of computational cost.

HIV Protease↗
PubMed2002

[The developing trend of the clinical laboratory].

The clinical laboratory technology has gradually changed the traditional detection methods. The new detection technology provides a more rapid and more accurate way for the disease diagnosis. The designs of the clinical laboratory equipments pay more attention to human factors, low cost and benefit for environment protection.

Clinical Laboratory Information Systems↗
PubMedDate not supplied

Protein transfer through polyacrylamide hydrogel membranes polymerized in lyotropic phases.

A way to control the average pore size in cross-linked polyacrylamide-based membranes is by altering the ratio of cross-linker to acylamide monomer. Larger pore sizes are prepared with a minimum amount of cross-linker, resulting in membranes that are mechanically weak and have short lifetimes. The aim of this study was to prepare cross-linked polyacrylamide membranes with large pore sizes and with good mechanical integrity. The methodology was to carry out the polymerization in a template, formed from the self-aggregation of surfactant. Two surfactant templates were used, and their pore size was examined with proteins of different sizes. The surfactants chosen for this study were sodium dodecyl sulfate (SDS, ionic surfactant) and TERIC BL8 (nonionic surfactant), both of which have very different aggregation properties. The data showed that at 10% and greater of TERIC BL8, a very different and open gel structure is formed, in which the pore size was significantly increased. SDS seemed to have little effect on the pore size. The data suggests that the gel structures for both surfactants up to 4% (w/v) are similar and micellular, because SDS is known to favor a micelle structure. Above 4% (w/v), TERIC BL8 then goes through a change in its lyotropic phase, thus, producing membranes of a large pore size. In conclusion, the pore size and gel structure of polyacrylamide hydrogel membranes can be significantly increased using TERIC BL8 (nonionic) surfactant. This allows large-pore-size membranes with a high cross-link density and consequently high mechanical strength to be prepared for the separation of large biomolecules.

Acrylic Resins↗