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)

1. The mast-cell distribution in the various layers of the ileum has been described.2. Histamine-content, anaphylactic histamine-release and the anaphylactic dose-response curve of the full-thickness ileum and of the longitudinal muscle strip have been measured and compared.3. Tetrodotoxin 10(-7) g/ml had no obvious effect on the anaphylactic dose-response curve of either preparation. This suggests that the plexus is not of any great importance in the Schultz-Dale reaction.4. Exposure of the longitudinal muscle strip to octylamine 10(-3) g/ml for 1 min reduced the mast cell content by 95-100%. After this treatment the dose-response curve to antigen was eliminated, although the muscle still responded to small doses of histamine and to anaphylactic mediators. Pretreatment of antibody with octylamine did not impair passive sensitization and subsequent response to antigenic challenge. This suggests that the classical Schultz-Dale reaction in the strip is mediated mainly by mast cells, and possibly other cells, and is probably not due to a direct effect of the antigen-antibody reaction on the smooth muscle.5. The typical three-phase anaphylactic response (quick contraction, quick relaxation, slow contraction) of full-thickness ileum is discussed and compared with the predominantly two-phase response of the longitudinal muscle strip. No evidence was found for the release of a relaxation-factor. It is suggested that the initial fast phase may be due to mediators released from mast cells among the longitudinal muscle fibres, and the sustained contraction to a second wave of mediators reaching the longitudinal muscle from deeper layers of the ileum.
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PMID:The Schultz-Dale response of the longitudinal muscle strip preparation of guinea-pig ileum. 409 38

The acute effects of deflazacort (MDL 458, CAS 14484-47-0) and its metabolite, 21-desacetyl-deflazacort, on allergic reactions in animal models were investigated and compared with those of prednisolone. Deflazacort, 21-desacetyl-deflazacort and prednisolone all inhibited 48-h homologous passive cutaneous anaphylaxis in rats, but had no significant effects on active systemic anaphylaxis in mice, on the Schultz-Dale reaction in the isolated guinea-pig trachea or on compound 48/80-induced histamine release in rat peritoneal mast cells. All three agents inhibited reversed cutaneous anaphylaxis in rats and the Arthus reaction in mice. The inhibitory effects of deflazacort on the passive cutaneous anaphylaxis, the reversed cutaneous anaphylaxis and the Arthus reaction were similar to those of 21-desacetyl-deflazacort and were stronger than those of prednisolone. Delayed type hypersensitivity in mice was also inhibited by deflazacort and 21-desacetyl-deflazacort, but prednisolone, at the doses used in the present study, had little effect on this immune response. These findings indicate that while deflazacort and 21-desacetyl-deflazacort have stronger anti-allergic effects than prednisolone, they seem to have little acute effect on mast cell degranulation or on chemical mediators at the receptor site.
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PMID:Acute effects of deflazacort and its metabolite 21-desacetyl-deflazacort on allergic reactions. 751 3

It has been shown that activation of protein tyrosine kinases (PTKs) is the earliest detectable signaling response to FcepsilonRI cross-linking on mast cells. Following tyrosine kinase activation, a family of mitogen-activated protein kinases (MAPKs) was found to be activated as well. Activation of this PTK signaling cascade will lead to mast cell degranulation. This review summarizes our recent studies on the role of PTK signaling cascade in an in vitro guinea pig model of allergic asthma using PTK inhibitors, genistein and tyrphostin 47, and MAPK kinase inhibitor, PD098059. Inhibitors of the PTK and MAPK signaling pathways significantly attenuated the ovalbumin (OVA)-induced bronchial anaphylactic contraction and enhanced relaxation of constricted airways, respectively, and substantially blocked the release of histamine and peptidoleukotrienes from chopped lung preparations induced by OVA. Based upon their substantial inhibitory effects on the Schultz-Dale reaction, further examination on the potential anti-asthmatic effects of PTK cascade inhibitors in an in vivo model of allergic asthma is recommended.
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PMID:Effects of inhibitors of the tyrosine kinase signaling cascade on an in vitro model of allergic airways. 1069 63

E-721B, an indigenous herbal combination was investigated for its usefulness in immediate hypersensitivity using different animal models. The drug inhibited the mast cell degranulation induced both by antigen and compound 48/80, the Schultz-Dale response in sensitized guinea pig ileum smooth muscle preparation and the production of precipitating antibodies in 50% of tested rats. It also inhibited the mast cell degranulation in passively sensitized rats indicating its suppressive action on production of reaginic antibody (IgE). However, the drug did not inhibit the 48 hours passive cutaneous anaphylaxis reaction in rats, indicating that a single dose of the drug does not have cromoglycate like properties. All the above results indicate the inhibitory effect of E-721B on immediate hypersensitive reactions such as asthma.
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PMID:Evaluation of E-721B, an indigenous herbal combination in experimental models of immediate hypersensitivity. 1188 71

Acquired agranulocytosis is a rare, life-threatening disorder. The few known causes/associations usually are readily identifiable (e.g., drug reaction, Felty syndrome, megaloblastosis, large granular lymphocytic leukemia, etc.). We report a novel association with mast cell disease. A 61-year-old morbidly obese man developed rheumatoid arthritis unresponsive to several medications. Agranulocytosis developed shortly after sulfasalazine was started but did not improve when the drug was soon stopped. Other symptoms across many systems developed including hives and presyncope. Marrow aspiration and biopsy showed only neutropenia. Serum tryptase was mildly elevated; urinary prostaglandin D2 was markedly elevated. Other causes were not found. Mast cell activation syndrome (MCAS) was diagnosed. Oral antihistamines, montelukast, and cromolyn were unhelpful; aspirin was initially felt contraindicated. Imatinib immediately increased neutrophils from 0% to 25% but did not help symptoms; subsequent addition of aspirin increased neutrophils further and abated symptoms. Different presentations of different MCAS patients reflect elaboration of different mediators likely consequent to different Kit mutations. Mast cells (MCs) help regulate adipocytes, and adipocytes can inhibit granulopoiesis; thus, a Kit-mutated MC clone may have directly and/or indirectly driven agranulocytosis. MCAS should be considered in otherwise idiopathic agranulocytosis presenting with comorbidities best explained by MC mediator release.
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PMID:Mast cell activation syndrome masquerading as agranulocytosis. 2233 92

Mastocytosis is a mast cell disease caused by functionally defective infiltrating mast cells and CD34+ mast cell precursors. The heterogeneous group of mast cell disorders is categorized into five variants in the updated 2017 World Health Organization (WHO) classification among those systemic mastocytosis with an associated neoplasm (SM-AHN). Except for myeloid neoplasia, lymphoproliferative disorders associated to SM-AHN are more scarce. Here, we report the second case ever described of associated mastocytosis and hairy-cell disease. A 38-year-old female patient without any specific medical history was diagnosed a hairy cell leukemia and BRAFV600E mutation was found in hairy cells. Since purine-analogs were avoided to prevent prolonged myelosuppression, she was treated with vemurafenib and rituximab. Despite early discontinuation due to vemurafenib-induced agranulocytosis, a partial response was observed. Strikingly, bone marrow biopsy performed one month after vemurafenib discontinuation revealed a nodular infiltration by 30% tumoral mastocytes. Along with elevated tryptase level, KITD816V mutation on mastocytes and clinical exam, the patient was diagnosed with systemic mastocytosis with an associated hematological neoplasm (SM-AHN). No BRAFV600E mutation was found on mastocytes. The physiopathology of this association is not known and might be only a coincidence or a common genetic driver mutation enhancing mast and hairy cells.
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PMID:Mastocytosis onset in a patient with treated hairy cell leukemia: Just a coincidence? 3179 34