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)

Mastocytosis comprises several diseases characterized by an abnormal increase in tissue mast cells. Cutaneous mastocytosis (CM) is the most common form of mastocytosis, affects predominantly children, and presents as a mast cell hyperplasia limited to the skin. Systemic mastocytosis (SM) comprises multiple distinct entities in which mast cells in filtrate the skin and/or other organs. The diagnosis of SM is based on the presence of one major criterion and one minor criterion or three minor criteria. Major criteria include the presence of multifocal dense infiltrates of > 15 mast cells in bone marrow and/or other extracutaneous organs. Four minor criteria include the presence of elevated serum alpha-tryptase levels > 20 ng/mL, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, the presence of a c-kit mutations on bone marrow and/or other tissues mast cells, and the presence of > 25% abnormal spindle-shaped mast cells in bone marrow and/or tissues. Symptoms of CM include pruritus, flushing urticaria, and dermatographism. Symptoms of SM include cutaneous symptoms in association with syncope, gastric distress, nausea and vomiting, diarrhea, bone pain, and neuropsychiatric symptoms. Activating and nonactivating mutations of c-kit (Asp816Val) are seen in adult SM and in some pediatric CM (Gly839Lys), indicating a clonal dysregulation. There is no cure for mastocytosis but the majority of pediatric CM regress at puberty. Women with mastocytosis are fertile and pregnancy and delivery have been successful by blocking mast cell-mediated symptoms. Symptomatic treatment aimed at reducing the effect of mediators is effective with antihistamines and mast cell-stabilizing agents such as sodium cromolyn. To reduce mast cell burden, interferon alpha, steroids, and purine analogs have been used with varying results. Future directions include tyrosine kinase inhibitors and bone marrow transplant.
Allergy Asthma Proc
PMID:Mastocytosis: classification, diagnosis, and clinical presentation. 1505 60

Azelastine hydrochloride 0.05% and olopatadine hydrochloride 0.1% are topical ocular allergy treatments that have demonstrated multiple pharmacologic actions, including antihistamine, mast cell stabilization, and inhibition of proinflammatory mediators. In this article, the mechanisms of action, efficacy, and tolerability of these two agents on ocular signs and symptoms are examined. By studying the various target sites of drug action, an enhanced clinical response algorithm of these topical ocular agents can be implemented to maximize the response for patients suffering from ocular allergy.
Curr Allergy Asthma Rep 2004 Jul
PMID:Ocular allergy treatment comparisons: azelastine and olopatadine. 1517 48

Asthma represents a chronic inflammatory process of the airways. The neurothrophin (NGF) and neuropeptides such as substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) play important role in stimulation of airways inflammation in asthmatics. NGF stimulates the differentiation and the migration of mast cells to bronchi epithelium. Furthermore, NGF stimulates mast cell degranulation and mediator upregulation and release. It also influences activity of basophils, eosinophils, neurophils, macrophages and T-cells. In addition, its important role in releasing of hyperresponsiveness has been proved. Neuropeptides such as CGRP and SP stimulate migration and degranulation of eosinophils and influence on airway responsiveness in asthmatics. This review article discusses the neuropeptides and NGF actions and mechanisms in the pathogenesis of asthma.
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PMID:[Role of neurotrophin and neuropeptides in bronchial asthma]. 1517 88

The pathogenesis of chronic idiopathic urticaria (CIU) is not understood completely; however, autoimmunity has been implicated. Because membrane and soluble forms of CD154 have been reported to be increased, in several autoimmune diseases, we have quantified the soluble CD154 (sCD154) molecule by a sandwich enzyme-linked immunosorbent assay in serum samples of 32 patients with CIU (aged 32 +/- 12 years) and compared them with 32 age- and sex-matched nonallergic controls. A marked increase was observed in patients with CIU as compared with controls (4.8 +/- 2.6 ng/mL versus 2.9 +/- 0.9 ng/mL; p < 0.0005). No significant differences were found between groups of patients with positive or negative autologous serum skin test. A biological assay to determine sCD154 showed that patients with positive autologous serum skin test have the highest levels (4.9 +/- 1.2 ng/mL) of biologically active sCD154 as compared with their negative counterparts (2.2 +/- 1.3 ng/mL; p < .001) and controls (0.6 +/- 0.3 ng/mL; p < 0.001). Active sCD154 can be derived from mast cell activation or other leukocytes. It is concluded that active sCD154 may be involved in the immune activation observed in patients with CIU.
Allergy Asthma Proc
PMID:Total and biologically active serum-soluble CD154 in patients with chronic idiopathic urticaria. 1517 97

Asthma is a disease of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma is still rising and is predicted to continue to rise in the current century. Inhaled beta(2)-adrenoceptor agonists and corticosteroids form the basis of the treatments available to alleviate the symptoms of asthma. There is a need for novel, safe treatments to tackle the underlying inflammation that characterizes asthma pathology. Furthermore, there is a requirement for new treatments to be developed as oral therapy in order to alleviate patient compliance issues, especially in children. A multitude of new approaches and new targets are being investigated, which may provide opportunities for novel therapeutic interventions in this debilitating disease. For simplicity, these approaches can be divided into two categories. The first comprises therapies directed against specific components or steps seen in allergic asthma. By 'components' we mean the key inflammatory cells (T cells [in particular T(h)2], B cells, eosinophils, mast cells, basophils and antigen presenting cells [APC]) and mediators (immunoglobulin E [IgE], cytokines, histamines, leukotrienes and prostanoids) believed to be involved in the chronic inflammation seen in asthma. By 'steps' we mean the allergic response, such as antigen processing and presentation, T(h)2-cell activation, B-cell isotype switching, mast cell involvement and airway remodeling. The other category of novel approaches to disease modification in asthma encompasses general anti-inflammatory therapies including phosphodiesterase 4 (PDE4) inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitors, peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, and lipoxins.
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PMID:New advances and potential therapies for the treatment of asthma. 1524 99

Asthma is characterized by variable airflow obstruction, airway hyperresponsiveness, and airway inflammation. Mast cells have long been thought to play a central role in asthma through their ability to release proinflammatory mediators, but this role has been questioned by the lack of efficacy of antihistamines and so-called mast cell-stabilizing drugs. Recent comparisons between the immunopathology of asthma and eosinophilic bronchitis have led to the re-emergence of the mast cell as a pivotal cell in asthma. Eosinophilic bronchitis is a condition in which patients present with chronic cough, and shares many of the inflammatory features associated with asthma, but without variable airflow obstruction or airway hyperresponsiveness. The only striking pathologic difference between these conditions is that, in asthma, the airway smooth muscle is infiltrated by mast cells. This suggests that interactions between mast cells and airway smooth muscle cells are critical for the development of the disordered airway physiology in asthma.
Curr Allergy Asthma Rep 2005 Mar
PMID:The re-emergence of the mast cell as a pivotal cell in asthma pathogenesis. 1568 13

Immunoglobulin E (IgE) is an important mediator in immediate hypersensitivity, as it facilitates mast cell degranulation and the release of immunomodulatory mediators, such as histamine, prostaglandins, and cytokines. Antigen-specific IgE is a hallmark of allergic diseases. Upon interaction with polyvalent antigen, IgE molecules crosslink and transmit signals that drive this process. Recently, an alternative function of IgE has come to light. Rather than merely priming the mast cell, in the absence of antigen, IgE influences mast cells, including their survival, receptor expression, and mediator release. The mechanisms by which IgE induces these effects and the biological consequences are being discovered and are showing that IgE has an important and active role in facilitating immune responses.
Curr Allergy Asthma Rep 2005 May
PMID:Antigen-independent effects of immunoglobulin E. 1584 55

Chronic idiopathic urticaria (CIU) is diagnosed in patients when urticarial eruptions recur for more than 6 weeks, and no specific cause is determined. Given that urticaria resembles the lesions induced by injection of histamine or allergen into the skin, a role for mast cells or basophils has been proposed in the generation of localized urticarial lesions. However, currently, the exact mechanisms governing regional mast cell or basophil activation are unknown. In the past decade, there has been mounting interest in viewing CIU as an autoimmune disease, given the presence of circulating autoantibodies to IgE or the alpha subunit of the high-affinity IgE receptor (FceRI) in a subset of patients. In this review, we propose that in addition to autoantibodies, specific differences in the expression of FceRI-signaling molecules in the basophils or mast cells of CIU patients may contribute to the generation of urticarial eruptions.
Curr Allergy Asthma Rep 2005 Jul
PMID:Basophils and mast cells in chronic idiopathic urticaria. 1596 67

Asthma is an allergic disease characterized by inflammation that includes an increase in the number and activation of mast cells in the airways. Glucocorticoids, on the other hand, diminish inflammation as well as the number of mast cells in this disease. Stem cell factor (SCF) is a major growth factor for human mast cells, inducing chemotaxis as well as survival of the mast cells. SCF induces proliferation and differentiation of immature mast cells from CD34+ progenitors. It also potentiates the IgE-dependent activation of mast cells. Furthermore, SCF expression is reduced in the airways of asthmatic patients treated with glucocorticoids. Thus, SCF could be involved in mast cell-associated diseases such as asthma. We here review the main effects of glucocorticoids in asthma and on mast cells, with a special interest on SCF, as a potential therapeutic target in asthma.
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PMID:Potential role of stem cell factor in the asthma control by glucocorticoids. 1610 70

Cardiac anaphylaxis refers to the functional and metabolic changes in the heart caused by the anaphylactic release of histamine and vasoactive products of arachidonic acid cascade by mast cells and basophils. As in most type I hypersensitivity-based diseases, histamine plays a key role in the pathophysiology of cardiac anaphylaxis. In the heart, mast cell activation and histamine release are controlled by multiple endogenous mechanisms, including adrenergic neural control, histamine-dependent negative feedback operated through H2 receptors, and the endogenous generation of nitric oxide (NO) and carbon monoxide (CO). All these mechanisms can be targeted by substances that have revealed a clear-cut effect in blunting cardiac anaphylaxis in experimental animal models, and could be developed as potential, novel anti-anaphylactic drugs. In this article, we discuss new findings and significant trends related to this topic.
Curr Allergy Asthma Rep 2006 Feb
PMID:Cardiac anaphylaxis: pathophysiology and therapeutic perspectives. 1647 89


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