Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enteric infection of mice with respiratory enteric orphan virus (reovirus) type 1, strain Lang elicits both humoral and cellular immune responses. To investigate the role of CD8+, alpha/beta T-cell receptor (TCR)+ T cells in mucosal immunity to an enteric pathogen, we examined immune responses and viral clearance following enteric reovirus infection in C57BL/6, B6129F2, and beta2-microglobulin-deficient (beta2m-/-) mice. Analysis of Peyer's patch and lamina propria culture supernatants revealed a two- to threefold increase in levels of reovirus-specific immunoglobulin A in beta2m-/- mice compared to normal controls. These data corresponded to a similar increase in the frequency of virus-specific immunoglobulin A-producing cells in Peyer's patches and lamina propria and an increase in immunoglobulin G-producing cells in spleens from beta2m-/- mice compared to controls. These increased humoral immune responses were not due to a difference in B-cell populations because cell counts and flow cytometric analyses showed that beta2m-/- and control mice had similar numbers and percentages of B cells in mucosal and systemic tissues. Analysis of cytokine message by reverse transcriptase-PCR 5 and 10 days after infection revealed no difference in message level for transforming growth factor beta, gamma interferon, interleukin-4, interleukin-5, or interleukin-6 for all mouse strains. Virus tissue titers determined by plaque assay at 5 and 10 days after infection demonstrated that beta2m-/- mice cleared reovirus from the small intestines with the same efficiency as control mice. Collectively, these data suggest that CD8+, alpha/beta TCR+ T cells may regulate mucosal and systemic humoral immune responses to oral infection with reovirus.
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PMID:Enhanced mucosal and systemic immune responses to intestinal reovirus infection in beta2-microglobulin-deficient mice. 922 66

The story of tumor immunology includes periods of hope followed by ones of disenchantment as far as clinical applications are concerned. In antiquity, cancer was considered "contrary to Nature", a concept which was confirmed by Ehrlich at the beginning of our century when the layed down the foundations of immunology. The latter was defined as the defence against all "non-self" intruders, including cancer, as opposed to the protection of "self". This concept was further accentuated by the theory immune surveillance proposed by Burnet in 1969 which implicated a destruction of nascent neoplastic cells by T lymphocytes. To increase host defence was the basis of tumor immunotherapy with BCG, levamisol and other adjuvants. The appearance of the nude mouse, athymic, and yet free of spontaneous tumors, led to a new paradigm, the network theory proposed by Jerne. This was based on immunological homeostasis implicating that both "self" and "non-self" can be rejected and tolerated. Cancer gradually ceased to be considered as "contrary to Nature". As for the proposed viral etiology of cancer which was the basis of the National Cancer Act signed by Nixon in 1971, this led to various breakthroughs and Nobel Prizes (Table 1), to discoveries such as reverse transcriptase, cellular oncogenes, tumor suppressor genes, which gave a new explanation for neoplastic transformation. The latter can now be considered as the consequence of a cascade of molecular events which include oncogene expression, anti-oncogene deletion, etc... converting, step by step, for instance, a polyp into a colon cancer and its metastases. The availability of monoclonal antibodies capable of attacking tumor cells did not lead to the expected success because of the complexity of the immune system. Attempts at a better understanding of the latter have led to a subdivision of the T lymphocyte CD4 population into Th1 and Th2. Th1 favor rejection (tumoral, fetal or of transplants) through the elaboration of IL-2, IFN and TNF while Th2 led to tolerance or acceptation through the production of IL-4, IL-5 and IL-10: both functions neutralize each other establishing a "normal" equilibrium Th1 vs Th2. This could explain the state of "tumor dormancy" or tumors in situ which are apparently quite frequent. That any immunological stimulation would cause these dormant tumors to proliferate is the basis of the immunostimulation theory proposed by Prehn and supported by the clinical observations of Stewart. This new concept has led some authors to propose that instead of destroying the tumor cells an attempt be made to maintain them in a state of dormancy in congenial company with normal cells.
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PMID:[A retrospective view of tumor immunology]. 922 70

Allergen immunotherapy (IT) involves subcutaneous injections of increasing doses of specific allergen over a period of time. It is recognised as highly effective in the treatment of patients with allergic rhinitis. However, the specific immunological mechanisms by which IT achieves its effect have not been fully elucidated. Recent studies, have shown that the clinical effects following IT of allergic individuals is concomitant with a reduced production of IL-4 by allergen specific CD4+ T-cells. The aim of the present study was to gain better knowledge about the immunological mechanisms by which IT exerts its beneficial effects. For this purpose, peripheral blood mononuclear cells (PBMC) from ten individuals receiving birch allergen or placebo in an IT-study performed in a double-blind manner, were analysed for IL-4, IFN-gamma, IL-5 and IL-10 mRNA expression at the onset of the study and during the pollen season, during treatment. Both spontaneous and in vitro allergen-induced cytokine mRNA expression was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). Spontaneous expression of IL-4 mRNA could be detected in most of the allergic patients, but not in healthy donors. The IT-treated patients showed a decrease in the spontaneous expression of IL-4 mRNA during the pollen season as compared to at the onset of the study, while in patients receiving placebo the IL-4 mRNA expression increased or remained unchanged. Similar results were obtained after in vitro stimulation with allergen. This was in contrast to the results for IFN-gamma, which was readily detected in both patient groups with no significant differences between the groups at either timepoint. IL-5 was shown to be increased during the pollen season in both groups and thereby presumably not affected by allergen IT. Taken together, these observations suggest that the cytokine profiles in circulating T lymphocytes change as a consequence of allergen IT.
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PMID:Allergen induced cytokine profiles in type I allergic individuals before and after immunotherapy. 923 48

The cytokine interleukin-5 (IL-5) selectively induces the proliferation, differentiation, and activation of mature eosinophils. The immunosuppressive agents cyclosporin A (CsA) and FK506 ameliorate the influx of eosinophils seen in allergic conditions such as asthma. We investigated the mechanisms controlling IL-5 messenger RNA (mRNA) expression in human T-lymphocytes in the presence of CsA or FK506. Fresh human peripheral blood mononuclear cells (PBMC); 7-day cultured PBMC, which represent a population of activated T-lymphocytes derived from PBMC; and the T-cell line HSB-2 were used. A novel polymerase chain reaction (PCR)-based nuclear run-on assay was employed to investigate the rate of IL-5 gene transcription. IL-5 mRNA degradation was measured by quantitative reverse transcriptase (RT)-PCR. CsA and FK506 strongly inhibited cellular IL-5 mRNA expression in response to phytohemagglutinin (PHA), or to phorbol myristate acetate (PMA), and/or calcium ionophore. Marked inhibition was observed in PBMC, 7-day cultured PBMC, and HSB-2 cells. Nuclear run-on assays done with either 7-day cultured PBMC or HSB-2 cells demonstrated striking inhibition of IL-5 gene transcription by both CsA and FK506 at levels reflecting the degree of reduction of total cellular IL-5 mRNA abundance. Neither CsA or FK506 had any detectable effect on the stability of IL-5 mRNA. Thus, the inhibitory effect of CsA and FK506 on cellular IL-5 mRNA expression can be explained by inhibition of the rate of IL-5 gene transcription.
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PMID:Cyclosporin A and FK506 reduce interleukin-5 mRNA abundance by inhibiting gene transcription. 927 13

The reasons why severe allergic reactions to bee and wasp stings develop in only a small portion of exposed individuals are incompletely understood, but differences in T cell responses to venom antigens comparing allergic and non-allergic individuals are likely to be important. To identify such differences, venom-induced proliferative responses and cytokine mRNA production by blood mononuclear cells from Vespula venom-allergic patients and non-allergic individuals were compared. Mononuclear cells from most venom-allergic patients proliferated in response to alkylated Vespula venom (7275 +/- 8387 ct/min, n = 19), and the extent of proliferation was greater for patients with a history of multiple prior stings and those with high levels of venom-specific IgE. Although mononuclear cells from non-allergic subjects showed little or no proliferation in response to venom (926 +/- 711 ct/min, n = 8), production of mRNAs coding for IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) in response to Vespula venom by cells from non-allergic subjects was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that these individuals had been previously sensitized to venom antigens. In contrast to the Th0 cytokine mRNA profile observed for non-allergic individuals, venom-allergic patients released a more restricted profile of cytokines following stimulation with venom. Only IFN-gamma mRNA expression was detected in all individuals evaluated, whereas IL-2 mRNA was not detected during the first 48 h of stimulation, and T cells from only one of three venom-allergic individuals produced detectable IL-4 or IL-5 mRNA. The difference in cytokine profiles observed comparing venom-allergic patients and non-allergic controls could not be attributed to intrinsic differences in T cells from these individuals, because polyclonal stimulation with phorbol myristate acetate (PMA) + ionophore induced similar cytokine mRNA profiles in the two groups. These studies demonstrate clear differences in the T cell responses of venom-allergic subjects, that may contribute to the development of severe allergic reactions in these individuals.
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PMID:Characterization of proliferative responses and cytokine mRNA profiles induced by Vespula venom in patients with severe reactions to wasp stings. 927 31

The regulatory functions of IL-12 on granuloma formation by the eggs of S. japonicum in the lungs of BALB/c mice were studied. Mice were injected i.v. with the eggs to induce the pulmonary granuloma. On days 0, 1, 2, 3, 7, 8 after injection, mice were injected i.p. with murine rIL-12 at a dose of 1 microgram day-1 (Group I) or 3 micrograms day-1 (Group II) or with PBS as a control (Group III). On day 10, all mice were sacrificed. The areas of pulmonary granulomas in histological sections were quantitatively measured by image analyser and the levels of mRNA for IL-10, IFN-gamma, IL-12 and IL-5 were assayed by reverse transcriptase PCR (RT-PCR). The results showed that the mean area per granuloma was significantly decreased in Groups I and II as compared with Group III. As for cytokine induction, IL-10- and IFN-gamma-specific bands appeared in Groups I and II, but not in Group III. Bands for IL-5 appeared in all groups, while bands for IL-12 were not detected in any group. It is suggested that IL-12 could inhibit the Th2 dominant granuloma formation induced by the eggs of S. japonicum.
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PMID:Effect of IL-12 on granuloma formation induced by injected Schistosoma japonicum eggs. 927 91

Atopic asthma is characterized by chronic inflammation of the bronchial mucosa in which eosinophil- and immunoglobulin E (IgE)-dependent mechanisms are believed to be prominent. Therefore, specific proeosinophilic mediators such as interleukin (IL)-5 and essential cofactors for IgE switching in B-lymphocytes such as IL-4 could play a pivotal role in asthma. However, the exact role that individual inflammatory mediators play in the development of the disease in humans is still unknown. Using semiquantitative reverse transcriptase-polymerase chain reaction amplification in bronchial biopsies from 10 atopic asthmatics, we have tested the hypothesis that IL-4 and IL-5 mRNA expression relative to beta-actin mRNA correlates with validated indicators of disease severity. IL-4 and IL-5 mRNA copies relative to beta-actin mRNA were detected in bronchial biopsies from atopic asthmatics. The numbers of IL-5 mRNA copies relative to beta-actin mRNA correlated with disease severity assessed by the Aas asthma score (r = 0.70, p = 0.01), baseline FEV1 (r = -0.94, p = 0.001), baseline peak expiratory flow rate (r = -0.77, p = 0.01), peak expiratory flow rate variability over 2 wk (r = 0.69, p = 0.028), and the histamine PC20 (r = -0.72, p = 0.018). Conversely, the numbers of IL-4 mRNA copies relative to beta-actin mRNA did not correlate with asthma severity, but they positively correlated with total serum IgE concentrations (r = -0.90, p = 0.001). Our present results support the concept that IL-5 may determine asthma clinical expression and severity, and by inference they support the development of IL-5 targeted therapies.
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PMID:Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. 930 82

The presence of mRNA transcripts for cytokines in normal and neoplastic human breast tissue has been investigated. Using reverse transcriptase-linked polymerase chain reaction (RT-PCR), we have specifically screened for the following cytokines: interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon (IFN)-gamma. No significant differences in expression of IL-1alpha, IL-1beta, IL-4, IL-6, TNF-alpha or TNF-beta were observed between the 2 groups of tissues. However, there was a significant difference in expression of IL-8 transcripts (p = 0.0017) which was higher in the neoplastic population. Transcripts for IL-2, IL-3, IL-5, IL-7 and IFN-gamma were not detected in either group. There was no evidence of associations between cytokine expression and tumour histological grade, patient age or lymph node metastases. Correlating tumour types with specific cytokine transcripts revealed high expression of IL-8, and to a lesser extent, IL-8 and TNF-beta irrespective of tumour origin. Analysis of primary epithelial and stromal cultures derived from both types of tissue showed that increased levels of IL-8, but not IL-6, were secreted by cells obtained from tumours. Thus, breast tissue of both normal and neoplastic origin expresses a wide range of cytokines. Increased or aberrant expression of cytokines, in particular IL-8, may be involved in the development/progression of breast cancer.
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PMID:Expression of cytokine messenger RNA in normal and neoplastic human breast tissue: identification of interleukin-8 as a potential regulatory factor in breast tumours. 937 54

Epstein-Barr-virus-associated posttransplant lymphoproliferative disease ranges from transient lymphadenitis to aggressive lymphoma. This study characterizes an in vitro model to study the pathogenesis of this disease with a cell culture system. Five B-cell lines derived from posttransplant lymphoproliferative disease tissue were characterized with regard to immunophenotype, karyotype, molecular genetics, cytokine production, and growth regulation. All cell lines expressed CD19, CD21, CD22, CD43, and CD77, but not CD10 antigens. Immunoglobulin light chain restriction was seen in four of five cell lines, and cytogenetic abnormalities were demonstrable in three of the five. Cells proliferating in culture contained multiple Epstein-Barr virus episomes and showed lytic viral replication. All cell lines produced tumor necrosis factor-beta and interleukin-10 without evidence of autocrine growth regulatory loops involving these cytokines. No evidence of IL-1 alpha, IL-2, IL-4, IL-5 or IL-6 production was found by reverse transcriptase polymerase chain reaction. Adding 500 U IFN-alpha/ml to the culture medium resulted in 30% inhibition of [3H]thymidine incorporation.
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PMID:In vitro culture of B-lymphocytes derived from Epstein-Barr-virus-associated posttransplant lymphoproliferative disease: cytokine production and effect of interferon-alpha. 946 86

Alveolar echinococcosis (AE) is a rare and often fatal disease characterized by a tumorlike expansion of the metacestode Echinococcus multilocularis in the liver. Because of the severe side effects of therapy with benzimidazoles, we treated a patient with recombinant interferon gamma at a dose of 250 microg over a 3-day period once a month. Disease progression was not detected during the observed period of 18 months. Following stimulation with crude Echinococcus antigen, mRNA from interleukin 5 was still detected in peripheral blood mononuclear cells by means of reverse transcriptase polymerase chain reaction analysis, and expression of interleukin 10 in T lymphocytes (as measured by fluorescence-associated cell sorting of intracellular cytokines) was elevated. These results indicate that bolus therapy with interferon gamma has some clinical effect but does not result in a change in the T helper 2 lymphocyte-dominated immune response to this parasite.
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PMID:Clinical efficacy of and immunologic alterations caused by interferon gamma therapy for alveolar echinococcosis. 950 76


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