Search

Interleukin (IL)-9 is a pleiotropic T helper 2-type cytokine that has been shown to be up-regulated in allergic airway disease, including asthma. IL-9 has been demonstrated to be a potent stimulus for the production and secretion of mucus from airway epithelial cells via induction of a calcium-activated chloride channel, hCLCA1. The objective of this study was to investigate the expression of IL-9 and hCLCA1 following allergen challenge in the nasal mucosa of allergic rhinitis patients. Nasal biopsies were obtained from allergic rhinitis patients out of allergen season both before (baseline) and after local antigen challenge with either ragweed or diluent (control). Immunohistochemistry and in situ hybridization were used to assess IL-9 protein and hCLCA1 messenger ribonucleic acid. Eosinophils and T cells were detected using immunohistochemistry. IL-9 and hCLCA1 were very low at baseline, and expression was significantly up-regulated following ragweed challenge. Whereas the number of eosinophils increased after allergen challenge, T-cell counts did not change significantly. The results of this study demonstrate the relationship between specific allergen challenge and expression of both IL-9 and hCLCA1, suggesting a possible mechanism for the increased production of mucus from airway epithelial cells in allergic rhinitis.

The optimal location of sales facility or branch factory of a firm entering a market area can be analyzed using a market-area based analytical method. Market boundary analysis shows (i) [...]

Presents a paper which incorporates interdependent relationship of firms and increasing consumer density into a framework of spatial equilibrium analysis and studies the location of firms and price system on a plane market. Behavior principle and basic assumptions; Analysis of a new firm's market entry; Formation of a non-uniform structure.

Provides information on a study which developed a guinea pig model of chronic asthma with markedly thickened airway walls by repeated antigen challenge in sensitized animals, to assess questions in regard to airway remodeling. Element which is thought to correspond to bronchial biopsy sites in humans; Overview of the model; Measurement of airway hyper-responsiveness.

Background: Asthma is characterized by a chronic inflammatory process involving high numbers of inflammatory cells and mediators which have multiple inflammatory effects on the airway. Interferon (IFN)-alpha, which is used widely for treating chronic hepatitis C, is reported to have an effect on patients with Churg-Strauss syndrome. Therefore, it may also be suitable for patients with severe asthma., Objective: We studied the effect of IFN-alpha on airway eosinophilia in a guinea pig model of asthma and the expression of adhesion molecules on human eosinophils and vascular endothelial cells., Methods: After antigen challenge, airway hyperresponsiveness and airway eosinophilia were measured in a guinea pig asthma model with or without airway IFN-alpha administration. Expression of adhesion molecules on eosinophils and cultured human umbilical vein endothelial cells (HUVECs) was also evaluated with or without IFN-alpha., Results: IFN-alpha inhibited eosinophil recruitment into the tracheal wall and improved airway hyperresponsiveness in sensitized guinea pigs. IFN-alpha also significantly suppressed IL-1 beta-induced intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. However, IFN-alpha did not suppress platelet-activating factor-induced macrophage antigen-1 expression on human eosinophils. IFN-alpha significantly inhibited eosinophil adhesion to IL-1 beta-induced HUVECs and migration through IL-1 beta induced HUVECs., Conclusion: The findings suggest that the modulation of ICAM-1 in lung with pre-existing inflammation following treatment with IFN-alpha may be a novel and selective treatment for control of chronic airway inflammation and hyperresponsiveness associated with asthma.

Background: Exacerbation of asthma has a negative impact on quality of life and increases the risk of fatal asthma. One of the known risk factors for patients with a history of near-fatal asthma is reduced sensitivity to dyspnea., Objective: We aimed to identify patients with such risk before they experienced severe exacerbation of asthma., Methods: We analyzed asthma symptoms and peak expiratory flow rate (PEFR) values of 53 patients recorded daily in a diary over a mean period of 274 days. Patients matched their symptoms to one of eight categories ranging in severity from 'absent' to 'severe attack'. We then analyzed the relationship between PEFR and asthma symptoms by dividing the PEFR value by the values of clinical parameters, including asthma symptom level., Results: Average PEFR was 75.2% (50.5-100%) in the 'absent' symptom category, 64.5% (36.6-92.6%) in 'wheeze', 57.3% (25.0-94.7%) in 'mild attack' and 43.6% (20.4-83.1%) in 'moderate attack', with the personal best reading taken as 100%. Thus, differences in PEFR in patients in the same symptom category varied widely. PEFR in wheeze, mild attack and moderate attack did not correlate significantly with duration of asthma, forced expiratory volume in one second or proportion of personal best to standard predicted PEFR values. These PEFRs showed no significant difference in groups divided by type of regular treatment, but showed a significant negative correlation with the coefficient of variation (CV) of PEFR when asthma symptoms were absent. CV for absent symptoms should be between +4.0 and -4.0% when using regression analysis to measure PEFR if the decreased PEFR is in agreement with guidelines., Conclusion: To determine which patients have reduced sensitivity to dyspnea, CV of PEFR should be considered when asthma symptoms are reported as absent. When patients present with more than 8% fluctuation in PEFR, we should intervene in their treatment, even when they claim to be stable.

Hypothesis: Activated CD8 as well as CD4 T cells contribute to the production of asthma-relevant cytokines in both atopic and nonatopic childhood asthma., Objectives: To measure the percentages of peripheral blood CD4 and CD8 T cells expressing naïve/memory (CD45RA/CD45RO) and activation (HLA-DR, CD25) markers, as well as mRNA-encoding interleukin-4 (IL-4) and interleukin-5 (IL-5) in atopic and nonatopic childhood asthmatics and in nonasthmatic controls matched for age and atopic status; and to study the effects of inhaled glucocorticoid therapy of the asthmatics on these measurements., Methods: Peripheral blood mononuclear cells were isolated from 17 atopic and 8 nonatopic stable (not acutely ill) asthmatics aged 7 to 16 years with moderate-to-severe disease and from 15 nonasthmatic controls matched for age and atopic status. Activation markers on CD4 and CD8 T cells were measured by flow cytometry, and expression of cytokine mRNA by in situ hybridization with CD4 and CD8 T cells were isolated using magnetic beads. Measurements were repeated in 18 of the asthmatics 4 to 6 months after initiation or escalation of inhaled glucocorticoid therapy for inadequately controlled asthma., Results: The percentages of CD4 T cells expressing CD45RO but not CD45RA were elevated in both asthma groups as compared with the relevant controls and were reduced in association with de novo or augmented inhaled glucocorticoid therapy. The percentages of CD8 T cells expressing both markers were not elevated in asthmatics as compared with controls. The percentages of both CD4 and CD8 T lymphocytes expressing HLA-DR and CD25 were elevated in the asthmatics as compared with controls, and significantly reduced in association with de novo or augmented inhaled glucocorticoid therapy. Elevated percentages of CD4 T cells expressing mRNA encoding IL-4 and IL-5, and CD8 T lymphocytes expressing IL-5, were found in asthmatics as compared with the controls. De novo or augmented inhaled glucocorticoid therapy was associated with significant reductions in the percentages of CD4 T cells expressing IL-5 and IL-4 mRNA, as well as improvements in lung function, symptom scores, and bronchial hyperresponsiveness to metacholine (PD20) in both the atopic and nonatopic asthmatics., Conclusions: The data are consistent with the hypothesis that both activated CD4 and CD8 T cells are associated with child asthma, and that CD4 T cells make a greater contribution to IL-4 and IL-5 synthesis. Increased dosages of inhaled glucocorticoid resulted in clinical improvement in the asthmatics along with reduced T-cell activation and cytokine mRNA expression, suggesting a possible causal association.