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)

Oxatomide is an orally active H1-histamine receptor antagonist which, as appears to occur with some other antihistamines, also inhibits mast cell degranulation. Oxatomide has demonstrated response rates similar to those with other more established members of its drug class in a few studies of chronic urticaria and allergic rhinitis. Interestingly, some patients responding to oxatomide were said to be unresponsive to previously administered antihistamines. The effect of oxatomide was little different from placebo in clinical trials of bronchial asthma in adults. While somewhat more encouraging results have been reported in children with bronchial asthma when higher than presently recommended dosages were employed, and in follicular conjunctivitis, atopic dermatitis and food allergy, reports to date are largely preliminary in nature and additional well-controlled studies are needed to clarify the efficacy of oxatomide in such conditions. The drug has been generally well tolerated, but shares some of the familiar H1-histamine receptor antagonist side effects. As with other similarly acting drugs, the 2 primary side effects with oxatomide are drowsiness and weight gain. Thus, on the basis of present evidence, a trial with oxatomide seems a potentially useful alternative in patients with conditions known or thought to be allergic in nature, in whom more established treatments were ineffective or poorly tolerated.
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PMID:Oxatomide. A review of its pharmacodynamic properties and therapeutic efficacy. 620 Feb 90

Cytological examinations of nasal mucosa were made on 60 patients with perennial allergic rhinitis. In the smear of all of the subjects mast cells and eosinophils were present in various quantities, depending on the intensity of the disease. A larger number were observed in periods of exacerbation than in remission. Mast cells were also found to be distinctly diverse morphologically. Apart from intact cells, mast cells of varying degranulation were also observed. Depending on the degree of degranulation, three types of cells were distinguished. On this basis it was assumed that changes in mast cell morphology may be due to changes of their function because of mucosa immunization. It is suggested that both mast cells and eosinophils should be acknowledged as diagnostic indicators in assessing the extent of allergic reactions of nasal mucosa.
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PMID:Mast cells in the cytology of nasal mucosa; a quantitative and morphologic assessment and their diagnostic meaning. 736 82

Allergic rhinitis is the sixth most prevalent chronic health condition in the United States. To study the pathogenesis of the allergic response, we have used a model of nasal provocation with antigen. During the initial reaction of an allergic subject to allergen provocation, increases occur in the levels of histamine, tryptase, and prostaglandin D2. This pattern of mediator release, combined with histologic evidence of mast-cell degranulation, strongly supports the role of the mast cell in the acute allergic reaction. The response to antigen, however, does not end with mast-cell degranulation. Hours after challenge we observed the spontaneous recurrence of symptoms and increased responsiveness to antigenic and nonantigenic stimuli. Our central hypothesis is that cellular infiltration and activation after antigen challenge are responsible for the observed increase in nasal reactivity. The predominant cells in nasal lavage 24 hours after challenge are eosinophils and neutrophils, whereas the predominant cell in the mucosa is the CD4+ lymphocyte. An early step in the movement of cells from the peripheral blood involves adhesion between circulating leukocytes and the endothelium. Evidence suggests that vascular endothelial adhesion molecule may be responsible in part for the selective adherence of eosinophils to the endothelium.
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PMID:Observations on the response of the nasal mucosa to allergens. 752 55

Human mast cells can be divided into two distinct phenotypes based on their content of neutral serine proteases, suggesting that they serve differing biologic and pathologic roles. Recently, it has been demonstrated that human mast cells are a source of several pleiotropic cytokines including IL-4, IL-5, IL-6, IL-8, and TNF-alpha, but not all mast cells contain all of these cytokines, suggesting that there is also functional heterogeneity with respect to cytokine expression. In this study, we have examined the relationship between mast cell neutral protease expression and cytokine content using immunohistochemistry. Bronchial mucosal biopsies from five normal subjects and five patients with allergic asthma, and nasal mucosal biopsies from five normal subjects and three patients with allergic rhinitis were embedded in glycol methacrylate. Sections (2 microns) were stained for IL-4, IL-5, and IL-6, adjacent to serial sections stained for tryptase and chymase. The distribution of cytokines among the tryptase+ chymase- mast cells (MCT) and tryptase+ chymase+ mast cells (MCTC) was examined by co-localization of cytokines to MCTC or MCT in serial sections using the camera-lucida. Although IL-4 was distributed among both mast cell phenotypes, it was expressed preferentially by the MCTC subset (overall 85% MCTC:15% MCT). In contrast, IL-5 and IL-6 were restricted almost exclusively to the MCT subset. Immunostaining of isolated skin mast cells (> 99% MCTC) supported these findings, with strong immunoreactivity present for IL-4 but very little for IL-5 or IL-6. These results indicate that in addition to exhibiting heterogeneity with respect to neutral protease content of the secretory granules, human mast cells are also heterogeneous with respect to cytokine content. This suggests that the biologic functions of MCTC and MCT cells differ as a result of their capacity to generate and release different cytokine profiles.
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PMID:Heterogeneity of human mast cells based on cytokine content. 760 7

Improved treatment approaches for seasonal allergic rhinitis are based on the increasing knowledge about allergic inflammation and on the improved efficacy of newer drugs. The current management concept includes an individualised composition of the different approaches including allergen avoidance, topical treatment and the use of systemic drugs and specific immunotherapy. Allergen avoidance, supported by pollen information, leads to a remarkable reduction of daily challenge situations. There is an increasing trend towards topical use of corticosteroids (e.g. budesonide and fluticasone) and mast cell stabilisers [e.g. sodium cromoglycate (cromolyn sodium), nedocromil and isospaglumic acid (N-acetylaspartylglutamic acid)] because of the potency of these drugs to impair the destructive activity of allergic inflammation. Potent histamine H1-receptor antagonists (e.g. azelastine and levocabastine) are approved for local treatment and lead to prompt relief of troublesome symptoms. A new generation of orally active antihistamines (e.g. astemizole, cetirizine, loratadine and terfenadine) have tended to be called 'antiallergics' because of activity other than H1-blockade. Furthermore, these newer compounds are less likely to cause sedation. Immunotherapy is still an integrated component in the treatment strategy. Standardised allergen extracts of high quality raise the treatment efficacy and safety. Overall, forming an individual combination of treatment approaches gives the best result.
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PMID:Seasonal allergic rhinitis. Newer treatment approaches. 768 72

Chronic sinusitis is a recurrent disorder commonly found in atopic individuals, yet few studies have explored the role of inflammatory mediators in sinusitis. Sinus lavage fluid from ten patients with chronic sinusitis obtained during endoscopic surgery was analyzed for total cell counts and then assayed for histamine, immunoreactive leukotriene C4/D4/E4 (LTC4/D4/E4), and prostaglandin D2 (PGD2). All ten patients had been unresponsive to medical treatment, including oral corticosteroids in most cases. High concentrations of histamine, LTC4/D4/E4 and PGD2 were found in sinus fluid and were comparable to levels seen in nasal secretions of allergic rhinitis patients following allergen challenge. In the sinus fluid, inflammatory cells were predominantly neutrophils with only low percentages of mast cells, basophils or eosinophils. On the basis of the histamine and PGD2 concentrations in sinus fluid, we conclude that mast cell/basophil activation does occur in chronic sinusitis and may contribute to the persistent inflammation present in sinusitis.
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PMID:Chronic sinusitis: characterization of cellular influx and inflammatory mediators in sinus lavage fluid. 771 57

This study was designed to compare the differences in morphology of the mast cells from the adenoid in children with otitis media with effusion (OME) and those from children with recurrent tonsillitis. Tissue for electron microscopy was prepared in the standard manner and between three and 10 blocks were examined for each child. All the mast cells with nuclei were photographed and the condition of the granules noted. The number of electron dense granules in each cell was assessed on a scale between zero and 10. Sixteen unselected children with OME were compared with 19 children with recurrent tonsillitis. There were no obvious differences in the degree of degranulation between the two groups although there was more vacuolation than previously described in the normal nose but less than in those patients with perennial allergic rhinitis. Allergy and mast cell reactions do not seem to predispose to OME. It was concluded that the adenoids are not the ideal tissue in which to study normal mast cells.
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PMID:Mast cell ultrastructure in the adenoids of children with and without secretory otitis media. 786 Oct 81

Tryptase, a neutral protease, is selectively concentrated in the secretory granules of human mast cells, and its release into the circulation serves as a clinical marker of mast cell activation. The current study describes a new, more sensitive ELISA utilizing a newly developed, mouse monoclonal IgG1 antibody for capture called B12 and capable of detecting tryptase in normal plasma and serum. The greater sensitivity of the new immunoassay results in part from a greater portion of tryptase being detected. Mean levels of tryptase in serum from normal subjects from Richmond, Virginia (4.9 ng/ml; n = 56), Munich, Germany (3.8 ng/ml; n = 19), and Amersfoort, The Netherlands (1.9 ng/ml; n = 8) were as indicated. In 62 subjects with ongoing allergic rhinitis, tryptase levels were no different in serum than for 19 normal controls, indicating that local mast cell activation is not necessarily reflected in the circulation. In 61 subjects sensitive to honey bee or yellow jacket venom by history, the 17 destined to have a severe, hypotensive response to a sting challenge had higher levels of tryptase at baseline than mild reactors, nonreactors, and controls, suggesting that baseline levels of tryptase may predict the severity of the clinical response to allergen in sensitive subjects.
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PMID:Development of a new, more sensitive immunoassay for human tryptase: use in systemic anaphylaxis. 792 94

The kinetics of mast cell accumulation in the nasal mucosa during allergen exposure were investigated in the animal model of experimentally induced allergic rhinitis. Guinea-pigs were divided into an unsensitized control group and five sensitized groups each containing five animals. Five sensitized groups were immunized intraperitoneally with ovalbumin, followed by intranasal administration of ovalbumin in each of four groups for 1, 2, 3 and 4 weeks, respectively. There were significant increases in the number of mast cells in the epithelium after 2 and 3 weeks in the groups receiving intranasal ovalbumin. No significant changes were detected in the lamina propria and the total number of mast cells. In the lamina propria, the distance between a mast cell and the basement membrane was significantly decreased in the groups after 2, 3 and 4 weeks of intranasal administration. These findings suggest that an infiltration of mast cells from the lamina propria to the epithelium occurred after 2 weeks of intranasal administration of allergen. An electron microscopic study showed no mast cells at the luminal surface of the epithelium and the majority of mast cells lying around the basal cells. This finding suggests that the allergen must penetrate into the epithelium in order to interact with mast cells in guinea-pig nose.
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PMID:Nasal mast cells in experimentally induced allergic rhinitis in guinea-pigs. 801 55

The role of Pavlovian conditioning in humans with perennial allergic rhinitis was investigated using release of tryptase from sensitised mast cells as an indicator of allergic responsiveness. Challenge with house dust mite allergen (unconditioned stimulus) was paired with a drink of novel taste and appearance (conditioned stimulus) in a single conditioning trial. Upon reexposure to the conditioned stimulus alone, levels of mast cell tryptase released in subjects who had received both the novel drink and allergen challenge on the conditioning trial was significantly greater than subjects who had received either the drink or the allergen alone. The results support the involvement of the central nervous system in mast cell degranulation in allergic rhinitis in humans.
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PMID:Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis. 802


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