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)

Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop sequelae of recurrent wheezing and asthma. To determine whether RSV persists within the lung after resolution of acute bronchiolitis, we examined the lungs of guinea pigs 60 days after intranasal inoculation with either human RSV (n = 10) or uninfected cell culture supernatant (n = 11). Evidence of viral persistence within the lung was determined by viral culture to test for replicating virus, immunohistochemistry to test for viral protein, and the reverse transcriptase-polymerase chain reaction (RT-PCR) to test for viral genomic RNA. Lungs were also examined histologically for evidence of bronchiolar inflammation or increased numbers of mast cells in the airway walls. All viral cultures were negative; however, there was positive immunohistochemical staining of occasional alveolar macrophages in six of ten RSV-inoculated guinea pigs while RT-PCR was positive in seven of ten RSV-inoculated animals. The six guinea pigs with evidence of RSV by immunohistochemistry and RT-PCR showed excess bronchiolar polymorphonuclear cell infiltrates (p < 0.005) but no increase in the number of airway wall mast cells. These results show that RSV protein and genomic RNA can persist in the lungs of experimentally inoculated guinea pigs for at least 60 days after infection and that persistence of the virus within alveolar macrophages might contribute to the pathogenesis of chronic bronchiolar inflammation.
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PMID:Persistence of respiratory syncytial virus genome and protein after acute bronchiolitis in guinea pigs. 820 87

Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma. Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself. The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay. All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.
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PMID:Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma. 856 17

Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients with the disease are skin test-negative to common aeroallergens, and have total serum IgE concentrations within the normal range. Nevertheless, the recent demonstration of increased numbers of cells expressing the high-affinity IgE receptor in bronchial biopsies from atopic and nonatopic asthmatic subjects, together with epidemiologic evidence indicating that serum IgE concentrations relate closely to asthma prevalence regardless of atopic status, suggests that IgE-mediated mechanisms may participate in the pathogenesis of both atopic and nonatopic asthma. Furthermore both variants of the disease are associated with bronchial mucosal eosinophilic inflammation. Interleukin-4 (IL-4) is an essential cofactor for IgE synthesis, and there is strong evidence that IL-5 plays a major role in eosinophil accumulation in asthmatic inflammation. For these reasons we compared the expression of IL-4 and IL-5 mRNA and protein product using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification, in situ hybridization, and immunohistochemistry in bronchial biopsies from symptomatic atopic and nonatopic asthmatic subjects and atopic and nonatopic controls. The results showed that as compared with controls, biopsies from both groups of asthmatic subjects had increased numbers of IL-4 and IL-5 mRNA copies relative to beta-actin mRNA as detected by RT-PCR. Similarly, in situ hybridization and immunohistochemistry demonstrated increased numbers of cells expressing IL-4 and IL-5 mRNA and protein in asthmatic subjects, irrespective of their atopic status. We conclude that individuals with either atopic or nonatopic asthma show infiltration of the bronchial mucosa with cells expressing Th2-type cytokines, providing further evidence for similarities in the immunopathogenesis of these clinically distinct forms of asthma.
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PMID:IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity. 891 71

Fiberoptic bronchoscopic methods have greatly improved our understanding of asthma pathogenesis and of the mode of action of established and experimental antiasthma drugs. It is probably most appropriate to study bronchoalveolar lavage (BAL) and bronchial biopsy simultaneously because there are major differences between the airway lumen and tissue compartments: for example, T cells are the most abundant cells in endobronchial biopsy samples but form only 10% to 20% of total BAL cells, and eosinophils and mast cells are more numerous in the airway tissue than in the lumina. Immunostaining is currently the most reliable method for enumerating cells and assessing their activation state with a panel of cell surface and intracellular activation markers. In situ hybridization can be used to study a cell's capacity for cytokine production. Newer techniques allow immunohistochemistry of adjacent cell sections to co-localize staining with different antibodies, showing for example that mast cells contain preformed cytokines IL-4, IL-5, and IL-6 and tumor necrosis factor-alpha A combination of immunohistochemistry and in situ hybridization can colocalize messenger RNA transcription to individual cell types; this approach is useful for T cells, which do not have storage capacity and cannot be shown by immunohistochemistry to contain cytokines. An additional tool to assess cellular activity is reverse transcriptase polymerase chain reaction, which has recently been used to confirm a predominant TH2-type cytokine profile in allergic disease.
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PMID:Bronchoscopy as a research tool for the study of asthma pathogenesis and effects of antiasthma drugs. 893 75

The selective recruitment of eosinophils into the mucosal lining of the airways is a prominent feature of atopic asthma, and is believed to be an important component in the disease pathogenesis. The precise stimuli responsible for the influx of eosinophils remain unclear. Using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique, the numbers of copies (relative to the "housekeeping" gene beta-actin) of messenger ribonucleic acid (mRNA) encoding the eosinophil-active chemotactic cytokines, the factor regulated upon activation in normal T-cells expressed and secreted (RANTES) and monocyte chemotactic protein-3 (MCP-3), was measured in bronchial biopsies from atopic asthmatic patients (n = 9), and compared with atopic nonasthmatic (n = 8) and nonatopic nonasthmatic (n = 8) control subjects. In addition, further biopsies from each subject were prepared for immunohistochemistry and the numbers of activated (EG2+) eosinophils measured. The expression of RANTES mRNA was significantly elevated in the atopic asthmatic group as compared to the atopic nonasthmatic controls (p = 0.013) and the nonatopic nonasthmatic controls (p = 0.007). Similarly, the expression of mRNA encoding MCP-3 was significantly elevated in the atopic asthmatic group, relative to the atopic nonasthmatic controls (p = 0.014) and the nonatopic nonasthmatic control group (p = 0.011). Elevated RANTES and MCP-3 mRNA expression was associated with significantly increased numbers of bronchial mucosal eosinophils in the atopic asthmatic patients as compared to the atopic nonasthmatic (p = 0.03) and nonatopic nonasthmatic (p = 0.006) control subjects. In conclusion, we have identified elevated expression of messenger ribonucleic acid encoding RANTES and monocyte chemotactic protein-3 in the bronchial mucosa of atopic asthmatic patients relative to controls. These findings are compatible with the hypothesis that eosinophil-active beta-chemokines play a role in the mechanism of eosinophil recruitment to the asthmatic bronchial mucosa.
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PMID:Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma. 898 Sep 53

Local secretion of cytokines by T cells within the bronchial mucosa, with consequent selective eosinophil influx, has been implicated in the pathogenesis of bronchial asthma. The cytokine IL-13 exhibits activities (selective eosinophil vascular adhesion by very late antigen-4/vascular cell adhesion molecule-1 interaction and promotion of IgE synthesis and "T112-type" T cell responses) that may be relevant to this process. We hypothesized that, compared with conditions in control subjects, elevated expression of messenger ribonucleic acid (mRNA) encoding IL-13 is a feature of the bronchial mucosa of both atopic (positive skin prick test result to at least one of a range of common aeroallergens) and nonatopic (negative skin prick test results and serum total IgE concentrations within the normal range) subjects with asthma. With use of a semiquantitative reverse transcriptase-polymerase chain reaction technique, we measured the quantities (relative to beta-actin) of IL-13 mRNA in bronchial mucosal biopsy specimens from atopic and nonatopic subjects with asthma and atopic and nonatopic control subjects. Biopsy specimens from the subjects with asthma, whether the subjects were atopic or nonatopic, had statistically equivalent quantities of IL-13 mRNA relative to beta-actin, and these quantities were significantly elevated compared with those in specimens from both the atopic and nonatopic control subjects (p < or = 0.02 in each case), in which the quantities of IL-13 mRNA relative to beta-actin were also statistically equivalent. The quantities of IL-13 mRNA reflected the numbers of EG2+ eosinophils per unit area of submucosa in the biopsy specimens as determined by immunohistochemistry, which were statistically equivalent in the atopic and nonatopic subjects with asthma and significantly elevated as compared with those in both the atopic and nonatopic control subjects without asthma (p < or = 0.007 in each case). Taking the subjects with asthma as a group, no correlations were observed between the quantities of IL-13 mRNA (relative to beta-actin) and several measures of disease severity. These data are consistent with the hypothesis that IL-13 plays a role in the pathogenesis of both atopic and nonatopic asthma, at least partly through promoting recruitment of eosinophils to the bronchial mucosa, although other factors may be more important in regulating the severity of the disease.
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PMID:Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. 915 33

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

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

T cells play a pivotal role in initiating and orchestrating allergic responses in asthma. The goal of this work was to learn whether ragweed challenge in the lungs alters the T-cell repertoire expressed in the blood and lungs of atopic asthmatics. Analyses of cell numbers, differentials, and T-cell subsets in bronchoalveolar lavage (BAL) fluids showed that ragweed challenge was associated with preferential recruitment of CD4+ T cells into the lungs. A reverse transcriptase-polymerase chain reaction (RT-PCR) was used to amplify T-cell receptor (TCR) gene transcripts from unfractionated, CD4+, and CD8+ T cells in blood and BAL fluids. As judged by RT-PCR, the usage of TCR Valpha and Vbeta gene families in BAL fluids was similar to that in blood. Ragweed challenge did not change the levels of expression of these V gene families. The clonality of T cells was estimated by analyzing the diversity of TCR V-(D)-J junctional region nucleotide lengths associated with each Valpha and Vbeta gene family, using sequencing gel electrophoresis. Most V gene families in blood and BAL fluids were associated with multiple junctional region lengths before and after ragweed challenge, indicating polyclonal expression. Some V gene families were expressed in an oligoclonal manner in unfractionated, CD4+, and CD8+ T cells in BAL fluids before ragweed challenge, as indicated by a few predominant junctional region lengths. The majority of these V gene families became polyclonal after challenge, compatible with polyclonal T-cell influx during inflammation immediately after ragweed challenge. However, some V gene families became oligoclonal or developed a new oligoclonal pattern of junctional region lengths in BAL T cells after ragweed challenge. Surprisingly, this occurred in both CD4+ and CD8+ T cells. In one of these instances, DNA sequencing of Vbeta21 junctional regions in CD8+ T cells confirmed a change from polyclonal to oligoclonal expression after ragweed challenge. These findings show that ragweed challenge is associated with polyclonal influx and oligoclonal activation of both CD4+ and CD8+ T cells in the lungs.
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PMID:T-Cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge. 949 Jun 55

The most frequent viruses associated with respiratory infections are human rhinoviruses (HRVs). Although the majority of HRV infections are mild and self-limited, HRV is an important cause of respiratory disease across all age groups. Recent studies using reverse transcriptase polymerase chain reaction to detect HRV genomes have established the importance of HRVs in predisposing to or causing otitis media, sinusitis and exacerbations of asthma, as well as other lower respiratory tract disorders. Among elderly people, infants and immunocompromised hosts HRV infections are often associated with lower respiratory tract morbidity and rarely mortality. How often active viral replication occurs in the middle ear, sinuses or the lower respiratory tract remains to be determined. However, the high incidence of HRV infections and their frequent association with upper and lower respiratory tract complications highlight the need for more effective means of prevention and treatment.
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PMID:Rhinoviruses: important respiratory pathogens. 992 Mar 54


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