Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics and function of human lymphocytes in tuberculous morbid site were studied. Exudative-sensitized lymphocytes in tuberculous pleural fluid reacted to the specific antigen more effectively and produced higher titers of cytokines including interferon gamma (IFN-gamma) than circulating lymphocytes. CD4+/CD8- T-cell subset is responsible for the antigen-specific IFN-gamma production in pleural T lymphocytes of patients with tuberculous pleurisy. Thus, activated T lymphocytes concern the production of cytokines at the morbid site and they effectively exert local cellular immunity through the action of such cytokines. Immunofluorescence study showed increased production of inducible nitric oxide synthase (iNOS) and peroxynitrite in BCG-inoculated human alveolar macrophages (AM). Reverse transcriptase-polymerase chain reaction methods also revealed the higher expression of iNOS-coding mRNA. Colony assay demonstrated that human AM effectively killed BCG in their cytoplasm. However, treatment of AM with NG-monomethyl-L-arginine monoacetate resulted in markedly reduced killing activity. These results clearly show that BCG-induced NO and its reactive product with the oxygen radical, peroxynitrite, could play an important role in BCG killing in human AM. We measured the pleural concentrations of IFN-gamma, interferon-gamma-inducing cytokines; interleukin (IL)-12 and IL-18 and interferon-gamma-inducible chemokines; IFN-gamma-inducible protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T cell alpha chemoattractant (I-TAC). These cytokines and chemokines in tuberculous pleural effusions were much higher than those in malignant pleural effusions. These findings indicate that IFN-gamma plays an important role in the cell mediated immunity in tuberculosis.
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PMID:[Tuberculous infection and biological response in man]. 1555 42

Recent data suggest that new treatment options for superficial bladder cancer are necessary, owing to the high recurrence rate after conventional treatment, especially in T1G3 and Bacillus Calmette-Guerin-refractory patients. Phase I and II studies have demonstrated that gemcitabine may represent a candidate for intravesical therapy in superficial bladder cancer. Despite clinical trials, the in-vitro cytotoxic and proapoptotic effects of gemcitabine have been poorly investigated. In the present study, we investigated how gemcitabine affects apoptosis in bladder cancer cell line 5637, which has the same molecular features of high-risk superficial bladder cancer. Apoptosis was evaluated by DNA fragmentation, flow cytometry and caspase activation. bcl-2, bcl-X, bax, survivin and fas gene expression were also evaluated by reverse-transcriptase polymerase chain reaction. Nuclear factor-kappa B activation was assessed by immunofluorescence. Gemcitabine induced apoptosis in 5637 cells in a time-dependent manner, with activation of caspase-3, -8 and -9. Expression of bcl-2, bax, survivin and bcl-X was not affected by treatment, whereas fas strongly increased after 24 h of treatment. After treatment, we failed to find any nuclear localization of nuclear factor-kappa B. As gemcitabine-induced apoptosis involves fas upregulation, these results may encourage the investigation of intravesical gemcitabine in fas-negative bladder tumors. Furthermore, as nuclear factor-kappa B activation by cisplatin, doxorubicin and adriamycin may result in enhanced proliferation, migration, immortality and inhibition of apoptosis, the observation that gemcitabine does not activate nuclear factor-kappa B may have implications in intravesical therapy of high-risk superficial bladder cancer.
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PMID:Gemcitabine-induced apoptosis in 5637 cell line: an in-vitro model for high-risk superficial bladder cancer. 1715 4

Mycobacterium tuberculosis CRP(Mt), encoded by Rv3676 (crp), is a CRP-like transcription factor that binds with the serC-Rv0885 intergenic region. In the present study, we evaluated CRP(Mt) 's regulation of serC and Rv0885 in M. tuberculosis and M. bovis BCG, using site-specific mutagenesis, promoter fusions and reverse-transcriptase PCR (RT-PCR). The CRP(Mt) binding site was required for full expression of serC and Rv0885, and expression of both genes was reduced in M. tuberculosis and M. bovis BCG crp mutants. These data show that CRP(Mt) binding directly activates both serC and Rv0885 expression. M. tuberculosis serC restored the ability of an Escherichia coli serC mutant to grow in serine-dropout medium, demonstrating that M. tuberculosis serC encodes a phosphoserine aminotransferase. Serine supplementation, or overexpression of serC, accelerated the growth of M. tuberculosis and M. bovis BCG crp mutants in mycomedium, but not within macrophages. These results establish a role for CRP(Mt) in the regulation of amino acid biosynthesis, and show that reduced serine production contributes to the slow-growth phenotype of M. tuberculosis and M. bovis BCG crp mutants in vitro. Restoration of serine biosynthesis by serC expression will facilitate identification of additional CRP(Mt)-regulated factors required by M. tuberculosis during macrophage and host infection.
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PMID:Dysregulation of serine biosynthesis contributes to the growth defect of a Mycobacterium tuberculosis crp mutant. 2190 33