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)

The inflammatory basis of asthma is now beyond dispute and even mild asthmatics exhibit mast cell degranulation, eosinophil infiltration and increases in mononuclear cells in airway mucosal biopsies. The chronic nature of this endobronchial inflammation may cause damage to ciliated epithelium, which, coupled with laying down of cross-linked collagen within the airway wall, leads to partly irreversible airway obstruction. Corticosteroids, which are potent anti-inflammatory agents, decrease bronchial hyperresponsiveness and the clinical manifestations of asthma. Although inhaled corticosteroids produce fewer side-effects, the use of low-dose (10 mg or less) oral treatment may be recommended for patients unable financially to afford inhaled corticosteroids or who are unable to use them effectively. Other anti-inflammatory drugs, including methotrexate, cyclosporin and the newer leukotriene inhibitors, are not yet in general use and may provide new pharmacological approaches to the treatment of asthma in the near future. In all but the mildest asthma, strategies aimed at preventing and decreasing bronchial inflammation should be the primary aim of treatment. The physician should refrain from prescribing only beta 2-agonists to new asthmatics and patients must be educated to increase understanding of the benefits of preventive rather than symptomatic forms of treatment for this chronic disease.
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PMID:Anti-inflammatory strategies for the treatment of asthma. 157 May 78

In strain-13 guinea-pigs inoculated for chronic relapsing experimental allergic encephalomyelitis (CR-EAE), IgG1 and IgG2 subclass antibody responses were investigated using single radial immunodiffusion and enzyme-linked immunosorbent assays (ELISA) for IgG1 and IgG2 specific for whole cord, myelin, myelin basic protein and Mycobacterium tuberculosis. The early acute stage revealed no increase in IgG1 but was associated with increased levels of IgG2 specific for neural and adjuvant components. Throughout the chronic phase of the disease, there were increased levels of IgG of both subclasses specific for the antigens tested but a preferential synthesis of IgG1. Levels of both IgG1 and IgG2 specific for neuroantigens were lowest in those guinea-pigs which did not develop signs of chronic disease. Immediate skin sensitivity against a wide range of neural antigens was not demonstrated though positive results may have been masked by the ability of myelin basic protein to induce non-specific mast cell degranulation and by altered histamine responsiveness in disease. Guinea-pigs with chronic paralysis had a lower skin sensitivity to histamine, compound 48/80 and M. tuberculosis than those in remission.
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PMID:IgG subclass responses and immediate skin sensitivity in guinea-pigs with chronic relapsing experimental allergic encephalomyelitis. 244 54

Chronic urticaria is a changeable disorder with an unknown length of duration. Thus, an objective method which could differentiate affected individuals from healthy individuals and with predictive information about when treatment might be diminished or stopped would be desirable. Therefore, we have tried to achieve this by means of Multitest, a device rendering good skin reaction reproduction and reagents such as 48/80 Compound (a nonspecific mast cell degranulator) and histamine. These substances were applied on 1 to 10(3) Mol concentrations for histamine and 10 to 10(3) mg/ml as the degranulating agent. Sixteen patients and 10 controls were submitted to this test, variables such as drugs modifying wheals, time of the day, age range and skin area were controlled. In both groups a clear dose-response relationship was demonstrated by either reagent. However, an excessive individual variability appeared in each sample and significant differences could not be shown so much for sensitivity or for reactivity (responses by the lowest and the highest concentrations, respectively). We conclude that the lack of differences observed on cutaneous mast cell "releasability" and skin vessels response to histamine in chronic urticaria patients could be due to a rather outstanding role of other cells and its mediators, in mechanisms of that chronic disease.
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PMID:Skin reactions to histamine and compound 48/80 in chronic urticaria: a diagnostic tool? 338 11

Previous studies have identified two ultrastructurally distinct forms of mast cell (MC) degranulation following activation. Immunoglobulin E (IgE)-mediated reactions are characterized by a very rapid swelling and fusion of MC granules and abrupt mediator release. In certain chronic disease states (e.g., bullous pemphigoid), there is "piecemeal" degranulation with a more-gradual mediator release effected by microvesicular transport of "pieces" of granules to the cell surface. It is unclear whether these two degranulation patterns are determined by the different natures of the stimuli, heterogeneity among responding MC granules, or temporal factors. To investigate these issues, we have carried out electron microscopic studies with skin biopsies obtained from ragweed-sensitive subjects 15 and 30 s and 1, 3, 5, and 10 min after intradermal ragweed injection. "Anaphylactic"-type granule changes began by 15 s after ragweed injection and were complete by 5 min; unaffected granules were juxtaposed with granules that were swollen and fused. The remaining granules subsequently underwent changes in appearance similar to those seen in piecemeal degranulation. However, microvesicular transport of granule components to the surface was not observed. These findings indicate that skin MC changes in sites of IgE-mediated reactions include not only the typical very rapid anaphylactic degranulation but also a slower onset of gradual alteration of other granules, frequently within the same MC. These different patterns could reflect MC granule heterogeneity with attendant different responses to IgE-mediated stimuli.
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PMID:Connective tissue mast cells exhibit time-dependent degranulation heterogeneity. 766 75

Systemic mastocytosis is a rare and chronic disorder characterized by a pathologically increased number of mast cells in various tissues and overproduction of mast cell mediators. From a group of 15 patients (10 females, 5 males) with systemic mastocytosis five female patients presented with a history of an anaphylactoid shock reaction to wasp sting. Three of them had no demonstrable specific IgE against wasp or bee venom in serum, and a skin test that was only weakly positive for wasp venom. One patient had specific IgE against wasp venom and a clearly positive skin test to wasp venom. The other patient had specific IgE against both wasp and bee venom and a skin test that was only weakly positive to wasp venom. Two patients had to stop a hyposensitization procedure because of systemic side effects. The five patients did not differ from the other patients with systemic mastocytosis with regard to either clinical symptoms and signs or urinary excretion of histamine metabolites. From the latter group two female and three male patients said they had been stung by a wasp in the past. Thus, anaphylactoid shock after Hymenoptera sting can be a presenting symptom of systemic mastocytosis and may be caused by an IgE- as well as a non-IgE-mediated mechanism. In cases of anaphylactoid reaction to Hymenoptera sting, especially when there is no IgE demonstrable in serum or in cases of intolerance of hyposensitization, the diagnosis of systemic mastocytosis should be considered, also in the absence of the clinical hallmarks of urticaria pigmentosa.
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PMID:Anaphylactoid shock following Hymenoptera sting as a presenting symptom of systemic mastocytosis. 845 Feb 93

Systemic mastocytosis is a chronic disease with proliferation of mastocytes in organs separate from skin. We report the case of a systemic mastocytosis revealed by a lymphocytic ascites in the absence of cutaneous involvement. The diagnosis was established by the ultrastructural examination of the bone marrow. Identification of few mastocytes in ascites suggested a mast cell infiltration of the peritoneum. A treatment by alpha-2b interferon was unsuccessful, and death rapidly occurred.
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PMID:[Lymphocytic ascites revealing systemic mastocytosis]. 874 56

We have recently phenotyped inflammation in non-infectious allergic and non-allergic chronic maxillary sinusitis using sinus biopsies and lavage fluids. In this first paper, we have concentrated our work on the eosinophil, T cell, mast cell and macrophage infiltrates. However, many unresolved questions remain and particularly the role of neutrophils needed to be addressed. In the present study, we focused on the neutrophilic inflammation: myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured by immunoassays and neutrophils were enumerated by conventional staining in the sinus lavage fluids of 16 patients with chronic sinusitis and six control subjects. Both MPO and IL-8 levels were significantly higher in patients than in controls (P < 0.01 and 0.005, respectively). There was a significant correlation between MPO levels and neutrophil numbers, and between MPO and IL-8 levels in the sinus lavage fluid (P < 0.0001, Spearman rank correlation). The presence of high levels of IL-8 in the lavage fluids of patients suffering from chronic sinusitis, levels which correlate with those of MPO, suggests that this cytokine may activate neutrophils in this chronic disease.
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PMID:Myeloperoxidase and interleukin-8 levels in chronic sinusitis. 920 88

Allergic conditions contribute significantly to the burden of chronic disease in the industrialized world. Current treatments offer varying degrees of palliation. The sole proven disease-modifying strategy, specific or whole-allergen immunotherapy, is limited because of the associated risk of systemic adverse effects, such as anaphylaxis. Short, linear allergen-derived peptides, corresponding to T cell epitopes, offer the possibility of a safer approach as they are capable of inducing allergen-specific hyporesponsiveness without cross-linking mast cell-bound IgE. This review evaluates the scientific basis of peptide immunotherapy and clinical experience in allergy up to the present time.
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PMID:The potential of peptide immunotherapy in allergy and asthma. 1189 95

Bronchial asthma is a chronic disease of the respiratory tract. Search for alternative to presently used therapies seems to be the way to obtain a better control of asthma. Heparin is an acidic mucopolysaccharide and in the past years there has been a number of reports on the role of heparin and low-molecular-weight heparin (LMWH) in chronic inflammatory disorders of the respiratory tract. Our aim was to estimate the effect of long-time LMWH nebulization on selected parameters in asthmatic patients. Twenty-four patients entered the study. All of them were subjected to bronchoscopy with BAL, in 8 patients this procedure was performed twice: before and after heparin treatment. After 14 days of treatment we observed an increase in FEV1 (from 73.93 +/- 14.14% (in % of nominal value) to 89.62 +/- 10.08% (p = 0.0049). Additionally we noted a decrease in the percentage of eosinophils and lymphocytes in BAL sediments, from 4.86 +/- 3.48% to 1.25 +/- 2.76%; p = 0.0006 and from 5.39 +/- 2.25% to 2.94 +/- 1.23%; p = 0.0209, respectively. This changes were paralleled by a drop of EG2 in BAL supernatant from 1.00 +/- 0.99 to 0.13 +/- 0.35, p = 0.0256. In blood serum level of histamine 0.74 +/- 0.77 to 0.1 +/- 0.22; p = 0.0493. We did not observe significant changes in IL-5, sVCAM-1 or ECP concentrations in serum. Also different LMWH dosing (5-10 kUIC anti-Xa b.i.d.) did not produce any dose-response effect. We conclude, that LMWH in nebulization can be a valuable add-on treatment in bronchial asthma, and its most likely mechanisms of action are: prevention of mast cell degranulation (histamine decrease), decreased eosinophil activation (lower EG2), and modification of inflammatory cells influx (decreased percentages of eosinophils and lymphocytes in BAL).
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PMID:[Mechanisms of action of nebulized low molecular weights heparin in patients with bronchial asthma]. 1505 58

Allergic conjunctivitis is in actuality a group of diseases affecting the ocular surface and is usually associated with type 1 hypersensitivity reactions. Two acute disorders, seasonal allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do 3 chronic diseases, vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis. The ocular surface inflammation (usually mast cell driven) results in itching, tearing, lid and conjunctival edema-redness, and photophobia during the acute phase and can lead to a classic late-phase response (with associated eosinophilia and neutrophilia) in a subset of individuals. As is the case in other allergic diseases, a chronic disease can also develop, accompanied by remodeling of the ocular surface tissues. In severe cases the patient experiences extreme discomfort and sustains damage to the ocular surface. For such cases, there is no highly effective and safe treatment regimen. Topical administration of corticosteroids is used in severe cases but is associated with an increased risk for the development of cataracts and glaucoma. Thus there is a worldwide search for new biotargets for the treatment of these diseases. Here we provide a brief update of the clinical symptoms associated with these diseases, the rationale for disease classification, recent advances in our understanding of the pathogenesis of the diseases, and an update on both preclinical and clinical advances toward refined therapies for these diseases.
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PMID:Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. 1563 56


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