Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bronchial biopsy specimens were obtained by fiberoptic bronchoscopy from 21 atopic subjects with asthma, 10 atopic subjects without asthma, and 12 normal healthy control subjects. With immunohistochemical techniques and a panel of monoclonal antibodies, inflammatory cells were identified and counted in the bronchial mucosa. The mean number of leukocytes (CD45+) and T-lymphocytes (CD3+, CD4+, and CD8+) at two airway levels in the subjects with asthma tended to be higher than in the other groups, but this difference did not achieve statistical significance. Similarly, there were no significant differences in the numbers of mucosal-type or connective tissue-type mast cells, elastase-positive neutrophils, or Leu-M3+ cells in the airway mucosa of subjects with asthma compared with atopic subjects without asthma and healthy control subjects. In contrast, significantly more interleukin-2 receptor-positive (CD25+) cells and "activated" (EG2+) eosinophils (EOSs) were present in the airways of subjects with asthma at both proximal and subsegmental biopsy sites. When the relationships between numbers of T-lymphocytes, activated (CD25+) cells, and EOSs were analyzed, there were positive correlations between CD3 and EG2, between CD3 and CD25, and between CD25 and EG2 positive cells in the airways of subjects with asthma. Furthermore, the ratio of EG2+ to CD45+ cells correlated with the provocative concentration of methacholine that caused a 20% decrease of FEV1 in hyperresponsive subjects. Although these associations do not prove a causal relationship, the results support the hypothesis that activated (CD25) T-lymphocytes release products which regulate recruitment of EOSs into the airway wall. In addition, our findings suggest that, in the large airways at least, asthma is not associated with hyperplasia of either mucosal-type or connective tissue-type mast cell.
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PMID:Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. 191 31

Various cells are associated with inflammatory events characteristic of atopic allergy and asthma. As well as T cells and eosinophils, mast cells, basophils, mononuclear phagocytes and platelets have all to be considered particularly as their mediators have potential for contributing directly to the features of bronchial asthma. Nevertheless, mast cell/T lymphocyte/eosinophil interactions may be of particular significance. For instance, the acute symptoms of allergy and asthma such as sneezing, bronchospasm and hives are believed to be largely the result of mediator release from mast cells whereas chronic symptoms (the result of allergic inflammation) can be explained on the basis of eosinophil-mediated tissue damage. Allergen is recognized directly by T cells. Specialized T cell subsets, possibly the Th2 equivalent, predominate in allergy and elaborate IL-4 (an essential co-factor for IgE production) and IL-5 which brings about terminal differentiation and activation of the eosinophil. Basic proteins derived from the crystalloid granule together with PAF and leukotrienes produce chronic wheeze, bronchial irritability, and might also be involved in permanent nasal blockage in chronic rhinitis. This general hypothesis is continually being tested. It is clearly important to identify precise molecular targets in allergy and asthma in order to construct therapeutic strategies.
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PMID:T lymphocytes and their products in atopic allergy and asthma. 193 73

While most asthma occurs in association with atopy, the relationship of this to clinical expression of the disease is not clearly understood. Allergen provocation causes an immediate bronchoconstriction (early asthmatic reaction) due to the release of mast-cell-derived histamine, prostaglandin D2 and leukotriene C4. The late reaction and attendent increase in bronchial responsiveness are associated with eosinophil influx, activation and mediator secretion, resulting in mucosal swelling in addition to smooth muscle contraction. Endobronchial biopsy and broncho-alveolar lavage have provided compelling evidence that both mast cells and eosinophils contribute to disordered airway function in 'clinical' asthma and that these cells are under the control of T lymphocytes. Topical corticosteroids which produce beneficial clinical effects probably do so by inhibiting those factors that maintain mast cell and eosinophil populations and their enhanced activation. The most likely contenders for these regulatory functions are the cytokines, particularly interleukin-3, -4 and -5.
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PMID:Allergic inflammation and its pharmacological modulation in asthma. 193 76

Flexible fibre-optic bronchoscopy under local anaesthesia has been used to investigate the cellular airway events in atopic asthma. The findings have been compared to those from atopic individuals without asthma and non-atopic healthy controls, in an attempt to discern those changes relevant to clinical disease expression. Immunohistochemical and electron-microscopic analyses of airway biopsies identified that an atopic diathesis is associated with tissue eosinophil infiltration and mast cell degranulation. The eosinophilia was greatest in those atopic individuals with asthma. Flow-cytometric analysis of airway lavage revealed significantly enhanced T lymphocyte activation in clinical asthma. These findings are consistent with the hypothesis that T lymphocyte activation, through cytokine release, amplifies the tissue eosinophilia in asthma and that this combination is associated with clinical disease expression.
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PMID:Airway inflammation and atopic asthma: a comparative bronchoscopic investigation. 193 87

A group of 187 asthmatics that had been using corticotherapy for at least a year was studied to ascertain the actual necessity of this treatment as well as the clinical and etiologic forms of bronchial asthma in these patients. Thus 3 categories of patients could be delineated; 112 patients with total (permanent) corticodependence, 25 patients with transient (seasonal) corticodependence and 50 patients with pseudocorticodependence. Generally, the category with total corticodependence consisted of patients with intrinsic asthma or with confirmed polyintricated allergic asthma. The criteria for inclusion in this category were: lack of response to bronchodilating treatment, estimated clinically and by FEV1 and/or Raw (resistance of air ways) determinations, and impossibility to achieve corticotherapy "sevrage" by associating mast cell-degranulation inhibitors (ketotifen and/or disodium chromoglycat--DSCG). In the other two categories corticosteroid sevrage could be achieved either transiently in the case of the second category (corticodependent patients only in the warm season--asthmatics with allergy to pollens, resistant to the usual treatment--or in the cold season--some asthmatics with infectious trigger) or completely in the patients of the third category (with pseudocorticodependence). In these latter subjects (about a quarter of the patients with prolonged corticotherapy), mostly asthmatics with ignored allergic etiology, the etiologic approach of disease and the association of Ketotifen and/or DSCG led to disappearance of corticodependence.
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PMID:Contribution to the study of the etiopathogenic and background peculiarities in patients with corticodependent bronchial asthma. Note I. Concepts of corticodependence and pseudocorticodependence. 194 11

The characteristics of the acute and late human response to antigen in the upper and lower airways and in the skin is summarized in TABLE 2. This table makes it clear that while mast cells are responsible for the mediator release of the acute phase, eosinophils and basophils are the cells involved in the mediator release which occurs during the experimental late phase reaction. The pattern of mediators observed during the acute response is quite characteristic of the mast cell. Thus, in the nose, skin, and lungs, the acute response is characterized by significant increases in histamine, PGD2, tryptase, and sometimes LTC4. In the late phase reaction, the pattern of mediator release is characteristic of basophils and eosinophils, and includes histamine, LTC4 (where measurable), and eosinophil-derived proteins, without PGD2 or tryptase. Basophils have been identified at appropriate time-points in each model using morphologic and phenotypic criteria, and their numbers relate to the histamine levels. Finally, treatment with glucocorticosteroids, the most potent drugs available for treating chronic allergic inflammation, obliterates the late phase reaction and decreases both mediator release and the infiltration of eosinophils and basophils. Chronic allergic inflammation is now taken by both the pulmonary and immunologic community as a hallmark of asthma, and it can be stated without equivocation that the basophils are responsible for the mediator release observed in that response.
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PMID:The role of basophils in asthma. 195 78

Inadequate reactions of the immune system, i.e. allergic or hypersensitivity reactions, may lead to lung tissue injury and possibly airway hyperreactivity. In extrinsic asthma, mast cells are considered to play a pivotal role in inducing hyperreactivity by producing various mediators. Immunoglobulin E is a well-known inducer of mast cell mediator release, and is thus often considered important. Asthma induced by a small molecular moiety such as toluene diisocyanate (TDI) is only in 15% of patients associated with increased IgE levels. TDI is a known inducer of cellular immune responses. We are investigating the relationship of type IV hypersensitivity, as an example of IgE-independent cellular hypersensitivity, with the induction of airway hyperreactivity. We have studied mice which were sensitized with picryl chloride. After antigen challenge in such sensitized mice, peribronchial and perivascular accumulation of macrophages and lymphocytes was highest 48 h after challenge. Two hours after challenge and from 7 days onwards no infiltration was found. At several time points after challenge, changes in smooth muscle tone of mouse tracheas were measured isometrically. The response to carbachol increased from 2 h after challenge, reaching a maximum 48 h after challenge and lasted for at least 3 weeks. This hyperreactivity was not found in athymic (nude) mice. We conclude from these preliminary data that airway hyperreactivity can be immunologically induced other than by IgE, and that in this model it is not associated with the presence of a mononuclear infiltrate. These experimental data indicate a potential role for T cells in inducing airway hyperreactivity, a common denominator of patients suffering from asthma.
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PMID:T cell-mediated airway hyperreactivity in mice. 195 13

Atopic dermatitis (AD), a common, multifactorial, and extremely complex disorder, should be examined from various points of view, and it requires all the skill a physician can gather because it can be a challenge for pediatricians, dermatologists, and allergists. The role of dietary factors in AD has long been a subject of controversies, and several investigators have demonstrated the effectiveness of elimination diets in the management of AD. The treatment of choice for AD due to food sensitivity (FS) is the elimination of the offending food(s). This can be easily achieved when the child is allergic to foods that are not common items in the diet or when the offending food is not an important nutrient. Problems arise when the child is allergic to food(s) common in the diet and/or that have a high nutritional value, SCG, the salt of a bischromone carboxylic acid, has been shown to be of some efficacy in the prophylaxis of bronchial asthma, allergic rhinitis, and other disorders associated with mast cell degranulation, such as mastocytosis. We reviewed 12 papers on the use of SCG in the management of AD children, which included 281 children aged 0.5 to 15 years. Analysis of the studies shows that five were carried out in the open, one in the single-blind, six in the double-blind fashion. Four out of five open trials yielded positive results, that is, SCG was effective in the management of AD. The double-blind studies were positive in three cases and negative in three. The only trial with doubtful results was conducted in the open fashion.
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PMID:Oral sodium cromoglycate in the management of atopic dermatitis in children. 195 71

Sympathomimetic bronchodilators with preferential specificity for the beta-2 receptor subtype are routinely used in asthma therapy. In addition to their ability to dilate bronchial smooth muscle following beta-2 receptor stimulation, these agents also inhibit mast cell mediator release and alter airway responsiveness. The importance of this class of drugs in asthma therapy has prompted the development of multiple asthma agents with the hope of achieving greater beta-2 receptor specificity, a quicker onset or more prolonged duration of action, a greater peak effect, or fewer side effects. This review compares the beta-2 agonists, as a group, with other asthma medications and, when data are available, makes comparison among various drugs within the group.
J Asthma 1990
PMID:Beta-2 receptor agonists in asthma: a comparison. 197 21

H1-receptor antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which histamine is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression. While there is considerable indirect evidence to implicate histamine in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity. In addition, H1-receptor antagonists have been shown to have effects on mast cell function. In low concentrations in vitro, antihistamines have been found to inhibit immunologically stimulated mast cell mediator release, with the IC50 in the nanomolar to micromolar range, while at higher concentrations they induce histamine release. The potency of these drugs in producing such effects is unrelated to their H1-receptor blocking activity. Furthermore the sedative effects of these therapeutic agents limit the tolerable administrable dose and thus the degree of H1-receptor blockade achievable within the airways. The recent development of H1-receptor antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of histamine in this condition. Furthermore, the receptor specificity of many of these agents has been focused such that terfenadine, astemizole, loratadine and cetirizine are devoid of anticholinergic activity and exhibit little alpha-antagonistic or anti-serotonin activity of clinical relevance. However, of these agents both loratadine and cetirizine possess additional actions likely to be of relevance to asthma. Pretreatment with loratadine has been shown to reduce the recovery of both histamine and prostaglandin D2 (PGD2) in nasal lavage fluid following nasal allergen challenge, a finding interpreted as indicative of in vivo mast cell stabilization, and cetirizine has been shown in vivo at therapeutic doses to inhibit allergen-induced eosinophil chemotaxis. Thus while both these agents offer the potential of an oral therapy for asthma based on an H1-receptor antagonist, their additional actions do not make them ideally suited to the exploration of the role of histamine in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Histamine and asthma: an appraisal based on specific H1-receptor antagonism. 197 6


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