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

Studies have demonstrated that increased amounts of histamine in the airways of asthmatic patients are associated with increased airway reactivity. However, using routine bronchoalveolar lavage (BAL), histamine can be detected in only a portion of asthmatic subjects and a minority of control populations. To obtain relevant mediators from the airways in higher concentrations by avoiding the dilution inherent with a standard BAL, a technique was developed to lavage isolated airway segments of the human lung that employed a double-lumen bronchoscope and a balloon-tipped catheter. Lavage fluid obtained by this method yielded significantly higher concentrations of histamine than that obtained with routine BAL (asthmatic subjects, 2,403 +/- 633 pg/ml vs 188 +/- 42 pg/ml; rhinitis subjects, 533 +/- 187 pg/ml vs 113 +/- 53 pg/ml; normal subjects, 174 +/- 63 pg/ml vs 11 +/- 11 pg/ml). Similar findings were also noted for prostaglandin D2 (PGD2). Segmental airway lavage also resulted in higher lavage fluid concentrations of LTB, than routine BAL. Segmental airway lavage should help in studying the relationship of mast cell degranulation to airways reactivity in both asthmatic and other study populations.
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PMID:Use of segmental airway lavage to obtain relevant mediators from the lungs of asthmatic and control subjects. 253 58

Previous studies have shown that pretreatment of skin with beta 2-adrenoceptor stimulants antagonizes anti-human IgE elicited wheal and flare reactions in atopic and non-atopic subjects. This experimental system was employed to further study the hypothesis that atopic disease and bronchial asthma unrelated to atopy might be associated with a beta-adrenoceptor defect. Eight patients with extrinsic and 10 patients with intrinsic asthma deprived of oral bronchodilator treatment and corticosteroids for at least a week, and in a clinically stable condition, 10 patients with extrinsic rhinitis and on no treatment, as well as age and sex matched healthy control subjects showed almost identical dose-response relations for the inhibitory effect of intradermally injected terbutaline (0.25-100 ng), on anti-IgE elicited skin reactions. In four asthmatic patients the inhibitory effect of terbutaline did not change following a treatment period with oral terbutaline and theophylline. The data do not support the presence of a cutaneous mast cell beta 2-adrenoceptor defect in patients with atopy or bronchial asthma unrelated to atopy.
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PMID:Equivalent inhibition by terbutaline of anti-human IgE skin responses in atopic and non-atopic subjects. 257 97

Research in molecular biology in the past few years offers new views on vasomotor rhinitis. The key role of mediator substances which contain the mast cell and which, after degranulation, are active immediately by histamine release or act in a delayed manner (eg. leucotriene), is discussed, as well as the "liberofunction" of the neurotransmitter acetylcholine. The contribution to vasomotor rhinitis of other humoral systems, the kinine system and complement factors are also taken into account. The biopharmacological actions of the effector systems of the nasal mucosa (vessels, exocrine glands, nociceptors) are also analyzed. Using clinical examples the differentiation between humoral or neural reflex mediated hyperreflexia is worked out related to the classic triad of sneezing, profuse nasal discharge, nasal obstruction. The causes of vasomotor rhinitis (exogenous endogenous and drugs) are examined in the light of their pathophysiological importance. The differential diagnosis must cover allergic rhinopathy as well as the different kinds of rhinitis medicamentosa, the most important of which are discussed. Drugs which can help are discussed as well as continuous physical therapy.
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PMID:[Hyperreflectoric rhinopathy]. 257 36

The way nasal polyps arise and why they tend to recur is still unknown. Quite frequently they are found in association with asthma, rhinitis and ASA-intolerance, thus suggesting a multifactorial etiopathogenesis. The incidence of atopy in patients affected with nasal polyposis is quite low (16.8%). Recent studies stress the involvement of mast cell mediators due to various degranulating stimuli other than those mediated by IgE. The finding of the interleukin-2 receptor (IL2-R) on murine mast cells and on human peripheral blood basophils, together with the possibility of inducing basophil degranulation through IL2 stimulation, have led the authors to seek IL2R on human nasal polyp mast cells and to study subpopulations of nasal polyp lymphoid infiltrates. Nasal polyps obtained from 4 patients, admitted to the E.N.T. Department of the Catholic University of Rome in 1988, were snap frozen soon after their surgical removal through transmaxillary ethmoidectomy. In this study the following monoclonal antibodies (MoAb) were used: Leu-2a (CD8), Leu-3a/3b (CD4), Leu-4 (CD3), anti-HLA-DR and anti-IL2-R (CD25), OKM1 (CD11), OKB2 (CD24) and 1HT4-4H3 (CD 25). In no patient was there evidence of atopy, asthma or ASA-intolerance. Several mast cells (MC) were observed, chiefly in the connective axis and perivascular areas. These cells were characterized by a large number of cytoplasmatic monomorphic granules. The MC displayed the IL2-R and they were very often close to T-lymphocytes. T-cell subpopulations were predominantly composed of CD4-positive cells (about 75% of all lymphocytes) often associated in clusters and located both in the submucosa and in the connective axis. CD8-positive cells (10-15% of the lymphoid cells) were located most often just under the epithelium. They were hardly ever scattered within the CD4-positive cell clusters. Almost all T cells were activated, above all those surrounding the MC. These results would appear to suggest the presence of a cell-mediated immune response in nasal polyp pathogenesis where MC degranulation, determined by activated T-cell cytokines, plays an important role.
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PMID:[Recent advances concerning etiopathogenesis of nasal polyposis]. 265 69

Review of the atopic diseases suggests a redefinition of the term "atopy" is indicated to reflect new information that has become available during the 60 years since the term was introduced. Atopy may be viewed as a manifestation of a still undefined defect. It is characterized by certain clinical findings and frequently by derangement of the immune and autonomic nervous systems. The atopic diseases are a group of seemingly unrelated conditions--eczema, asthma, rhinitis, hypertrophic sinusitis, and perhaps vernal conjunctivitis and migraine--which cluster in individuals and families. In the respiratory tract and eye, eosinophils in the tissues and secretions are characteristic and are not dependent on the presence of immediate hypersensitivity. Symptoms suggestive of basophil and mast cell mediator release are common to all the atopic diseases, and there is some evidence that nonimmunologic mediator release is enhanced in atopic patients. In the most clearly defined atopic diseases, eczema and asthma, approximately 80% of patients have an increased IgE response to normal environmental allergens. Accompanying and perhaps underlying these enhanced IgE responses are deficiencies of T cell numbers and function particularly in the suppressor T lymphocytes. Evidence exists that decreased beta-2-adrenergic and increased cholinergic and alpha-adrenergic responsiveness accompany and perhaps underlies the atopic diseases irrespective of the presence or absence of allergy.
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PMID:The Bela Schick lecture for 1985. The atopic diseases. 286 4

Rhinitis may be classified as infectious (purulent), seasonal allergic, perennial allergic, perennial nonallergic (vasomotor) and nasal polyps. Pharmacotherapy can be local or systemic. A variety of compounds are available, including alpha adrenergic agonists, mast cell stabilizing agents, Beta-2 agonists, antihistamines, cholinergic antagonists and corticosteroids. In terms of histamine receptors, H1 receptors predominate in the epithelium and glands but both H1 and H2 receptors are present in nasal blood vessels. Trigeminus-reflex mediated nasal secretions, can be treated by parasympatholytic drugs.
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PMID:Pharmacotherapy of nasal disease. 288 12

There is little or no direct in vivo evidence in man to support the involvement of mast cell-mediator release in the pathogenesis of immediate allergic reactions. We have performed a within-subject controlled study to determine the changes that occur in nasal mast cells during allergen-induced rhinitis. Twelve subjects with asymptomatic rhinitis were studied. Nasal biopsy specimens were obtained from each subject after a control solution (isotonic saline, 0.9% w/v) had been nebulized into one nostril and allergen solution (freeze-dried allergen extract reconstituted with isotonic saline) into the other. The tissues obtained were fixed in Carnoy's solution and stained with the alpha-naphthol AS-D chloroacetate esterase reaction (N AS-D CA ER). Mast cells were counted under light microscopy in the epithelium and lamina propria, and the integrity of each cell was assessed. No significant differences were found in the number of epithelial or lamina propria mast cells in biopsy specimens obtained after saline or allergen administration. However, the number of degranulated mast cells after allergen provocation (89%) was significantly greater than after instillation of control solution (15%) (p = 0.003). Changes of mast cell degranulation after allergen provocation were confirmed by electron microscopy. In six nonatopic, control subjects without rhinitis, there was no significant difference between the percentages of degranulated mast cells after allergen provocation (25.8%) and instillation of saline (24.3%). This study provides direct in vivo evidence for allergen-induced mast cell activation in man.
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PMID:Direct in vivo evidence for mast cell degranulation during allergen-induced reactions in man. 309 10

Nasal lavage after antigenic and nonantigenic nasal stimulation has become an important tool for the study of inflammatory phenomena in the upper airway. Biochemical and cytologic information is relatively easily obtainable, and pharmacologic manipulations can be readily monitored. This article is of several studies aiming toward a more profound understanding of the mechanisms of allergic and nonallergic rhinitis by the use of laboratory-challenge procedures and nasal-lavage techniques. An early and a late reaction are detected clinically in the nose after antigen challenge of allergic individuals. In addition, the sensitivity to antigen significantly increases after the initial challenge, and this phenomenon is not obligatorily linked to the presence of a late-phase reaction (LPR). Inflammatory mediators, mostly mast cell- and/or basophil-derived, are detected in the nasal washes and correlate with the symptomatology in both the early and the late reactions. The allergen-induced LPR is marked by an early influx of eosinophils and, later, basophils and neutrophils. Elevation of major basic protein and histamine, but not prostaglandin D2, is detected during the LPR, giving evidence of active eosinophil and basophil participation. Systemic steroids can effectively suppress the clinical, biochemic, and cellular manifestations of antigen-induced LPR. Topical steroids have a similar effect but are also capable of suppressing the early reaction to antigen. A nonallergic form of rhinitis can be induced in the laboratory by nasal inhalation of dry air at freezing temperatures in individuals who report sensitivity to cold and windy environments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the allergic and nonallergic nasal inflammation. 328 18

Kinins are generated in nasal secretions during allergic reactions and during induced rhinovirus colds. To determine if kinins may contribute to the symptomatology of these inflammatory reactions, 8 subjects were challenged with increasing doses of bradykinin or with placebo. Levels of albumin, histamine, and N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase were measured in nasal lavages, and symptom scores were noted. No symptoms or increases in mediators or protein were observed after placebo challenge. Symptom scores increased in a dose-dependent manner, however, in response to bradykinin challenge. Increased symptoms were associated with significant increases in albumin and TAME-esterase activity, but no increases in histamine were observed. Nasal conductance measurements confirmed that bradykinin induces dose-dependent unilateral obstruction in the challenged nostril. Other common symptoms were rhinorrhea and, of particular relevance to rhinovirus infections, a persistent sore throat. We conclude that bradykinin causes increased vascular permeability and rhinitis, which are independent of mast cell mediator release. Kinins may, therefore, contribute to the symptomatology of inflammatory reactions of the upper airways, including the common cold.
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PMID:Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat. 334 41

In vivo studies have shown that human C5a, a potent complement-derived anaphylatoxin and chemoattractant, produces immediate inflammatory reactions following intradermal injection in human skin. At concentrations within its potential physiologic range, intradermal injection of C5a elicits immediate wheal and flare reactions, increased vascular permeability, mast cell degranulation, and neutrophil-rich infiltrates. To assess the relative contribution of interacting cellular elements to C5a-induced inflammation in normal human skin, purified human C5a was tested intradermally in 8 patients with bone marrow failure (BMF). Reactions to C5a in patients with BMF were compared with responses at identical test sites in healthy volunteers and other patients with cutaneous disorders. Patients with BMF demonstrated significantly less wheal and flare reactivity following intradermal injection of C5a than controls (p less than 0.05 and less than 0.02, respectively). In these studies, patients with the greatest cytopenia generally showed the least cutaneous reactivity to human C5a. Biopsies of C5a test sites in patients with BMF revealed an absence of leukocytes in marked contrast to neutrophil-rich infiltrates observed at test sites in healthy volunteers. Avidin-fluorescent and/or Giemsa staining of skin biopsies revealed no difference between the number of dermal mast cells in patients with BMF and samples of normal human skin. In addition, skin test studies with histamine (2 micrograms) and morphine (5 micrograms) performed to assess cutaneous vascular and mast cell responsiveness in patients with BMF, normal volunteers and controls with rhinitis revealed no significant differences in cutaneous reactivity to these pharmacologic agents. These in vivo studies demonstrate that patients with BMF specifically exhibit decreased cutaneous reactivity to human C5a and suggest that neutrophils make an important and an immediate contribution to inflammatory responses elicited by this anaphylatoxin.
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PMID:Patients with bone marrow failure demonstrate decreased cutaneous reactivity to human C5a. 355 64


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