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)

Systemic Sclerosis is a multisystemic disease characterized by sclerosis of the skin and visceral organs, vasculopathy (Raynaud's phenomenon) and autoantibodies. The criteria for the classification of the disease requires either proximal scleroderma (major criteria) or the presence of 2 of the 3 minor features namely sclerodactyly, digital pitting scars and bibasilar pulmonary fibrosis. There are 3 subsets of this condition--diffuse variant, limited variant (CREST syndrome) and Overlap Syndrome (where patients have features of other rheumatic diseases). There are localized forms of scleroderma and pseudoscleroderma states. The presenting features of Systemic Sclerosis are usually Raynaud's, skin changes and arthralgia. Systemic complaints like breathlessness, dyspepsia, etc depending on the organ involved may be present. Management starts with patient education regarding the disease, skin care, exercises and regular medical check-up. There is no miracle cure but much can be done to improve the quality of life of the patient. Nifedepine and other drugs may improve Raynaud's phenomenon. Drugs can be used to treat other complications. Various medication have been tested as disease modifying drugs for scleroderma. These include drugs which inhibit collagen like D-penicillamine, colchicine, and immunosupressive drugs like cyclosporin. Ketotifen, a mast cell stabilizer has been reported to be effective in scleroderma. As it is a relatively safe drug, clinical trials are underway.
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PMID:Systemic sclerosis. 162 Nov 27

The gastrointestinal tract is a rich source of mast cells with an enormous surface area that permits a high degree of interaction between the mast cell and intestinal luminal contents. The active metabolic products of the mast cell influence gastrointestinal secretion, absorption, and motility through paracrine effects of local mast cell degranulation and also cause systemic effects through the release of cellular products into the blood stream. Systemic mastocytosis influences physiologic function through the systemic effects of mast cell products released from focal (e.g., bone marrow) or wide spread increases in mast cell number. Local gastrointestinal proliferation of mast cells in response to recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter gastrointestinal function and induce systemic symptoms. Celiac sprue, inflammatory bowel disease, and non-ulcer dyspepsia are three examples of gastrointestinal diseases in which mast cells can be implicated in the pathophysiology of the symptoms.
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PMID:The role of the mast cell in clinical gastrointestinal disease with special reference to systemic mastocytosis. 200 61

Both eosinophils and mast cells have been implicated in the generation of abdominal pain. The purposes of this retrospective study were to determine the prevalence of duodenal eosinophilia in pediatric dyspepsia and to determine the clinical response rate of these patients to combined H1 and H2 receptor antagonist and mast cell stabilizer therapy. Fifty-nine patients (ages 3.5-17.7 years) with dyspepsia undergoing endoscopy were evaluated. All patients had a minimum of 2 forceps biopsies obtained from each of the esophagus, antrum, and duodenal bulb. Routine histologic evaluation was performed and duodenal biopsies were additionally evaluated to determine eosinophil counts. Patients with > 10 eosinophils/hpf were treated with ranitidine and hydroxyzine (H1/H2). Nonresponders were then treated with oral cromolyn. Patients were followed up and response recorded in an abdominal pain database and/or medical chart, which were reviewed for this study. Forty-two patients (71%) had duodenal eosinophilia. Twenty-one (50%) of these were responders to H1/H2. The response rate did not differ between patients with and without noneosinophilic esophagitis, gastritis, or duodenitis, respectively. Two patients were lost to follow-up and considered nonresponders. Seventeen of the remaining 19 (89%) were responders to cromolyn. Overall, the response rate to this treatment pathway was 90%. Duodenal eosinophilia is common in pediatric patients with dyspepsia. These patients appear to be clinically amenable to combination H1/H2 therapy and/or oral cromolyn.
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PMID:Mucosal eosinophilia and response to H1/H2 antagonist and cromolyn therapy in pediatric dyspepsia. 1652 34

The gastrointestinal tract is a rich source of mast cells with an enormous surface area that permits a high degree of interaction between the mast cell and intestinal luminal contents. The active metabolic products of the mast cell influence gastrointestinal secretion, absorption, and motility through paracrine effects of local mast cell degranulation and also cause systemic effects through the release of cellular products into the blood stream. Systemic mastocytosis influences physiologic function through the systemic effects of mast cell products released from focal (e.g., bone marrow) or wide spread increases in mast cell number. Local gastrointestinal proliferation of mast cells in response to recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter gastrointestinal function and induce systemic symptoms. Celiac sprue, inflammatory bowel disease, and non-ulcer dyspepsia are three examples of gastrointestinal diseases in which mast cells can be implicated in the pathophysiology of the symptoms.
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PMID:The role of the mast cell in clinical gastrointestinal disease with special reference to systemic mastocytosis. 1679 7

The aims of the current study were to determine the activation states of antral eosinophils and mast cells and to evaluate the interactions of antral inflammatory cells with gastric emptying and electrogastrography (EGG) in 30 pediatric patients with functional dyspepsia. Eosinophil degranulation was moderate in 42% and extensive in 54% of patients. Mast cell degranulation was > 50% in 81% of patients. Elevated mast cell density was associated with slower one hour gastric emptying and increased preprandial dysrhythmia. Mast cell density correlated with the preprandial percentage tachygastria. CD3+ cell density correlated with the preprandial percentage tachygastria also, but only in patients with increased eosinophil density. In conclusion, antral eosinophils and mast cells are significantly activated in pediatric functional dyspepsia. Mast cell density is associated with delayed gastric emptying and preprandial dysrhythmia, suggesting that there may be an interaction between antral inflammation and gastric electromechanical dysfunction in the pathophysiology of pediatric functional dyspepsia.
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PMID:Antral inflammatory cells, gastric emptying, and electrogastrography in pediatric functional dyspepsia. 1832 Mar 15

The eosinophil-mast cell-neural pathway may be important in the pathophysiology of functional gastrointestinal disorders characterized by unexplained abdominal pain, disordered defecation, or meal-related discomfort. There is evidence that duodenal eosinophils are increased in functional dyspepsia, whereas mast cells are increased in the lower gut in irritable bowel syndrome, directly supporting a role for a hypersensitivity-type reaction in these disorders. The trigger may be a pathogen, food, or other allergen in the gut mucosa. This trigger may evoke eosinophils, mast cells, and other components to cascade to up-regulate serotonin release, with modulation of the enteric and central nervous systems, creating a vicious cycle. If correct, this theory suggests treatment should specifically target the eosinophil-mast cell pathway.
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PMID:Functional gastrointestinal disorders and the potential role of eosinophils. 1849 26

Mast cell disorders are defined by an abnormal accumulation of tissue mast cells in one or more organ systems. In systemic mastocytosis, at least one extracutaneous organ is involved by definition. Although, systemic mastocytosis usually represents with skin lesion called urticaria pigmentosa, in a small proportion, there is extracutaneous involvement without skin infiltration. Other manifestations are flushing, tachycardia, dyspepsia, diarrhea, hypotension, syncope, and rarely fever. Various medications have been used but there is not a definite cure for systemic mastocytosis. The principles of treatment include control of symptoms with measures aimed to decrease mast cell activation. We describe a case of systemic mastocytosis presenting with hypotension, syncope attacks, fever, and local flushing. In bone marrow biopsy, increased mast cell infiltration was demonstrated. She had no skin infiltration. A good clinicopathological response was obtained acutely with combination therapy of glucocorticoid and cyclosporine.
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PMID:Hypotension, Syncope, and Fever in Systemic Mastocytosis without Skin Infiltration and Rapid Response to Corticosteroid and Cyclosporin: A Case Report. 2120 30

Accumulation of mast cells can be causally related to several allergic inflammations. Stem cell factor (SCF) as a mast cell chemotaxin induces mast cell migration. To clarify a new effect of Pyeongwee-San extract (KMP6, a drug for indigestion) for the treatment of allergy, we investigated the effects of KMP6 on SCF-induced migration of rat peritoneal mast cells (RPMCs). A molecular docking simulation showed that hesperidin, a major component of KMP6, controls the SCF and c-kit binding by interaction with the active site of the c-kit. KMP6 and hesperidin significantly inhibited SCF-induced migration of RPMCs (P<0.05). The ability of the SCF to enhance morphological alteration and F-actin formation was also abolished by treatment with KMP6 or hesperidin. KMP6 and hesperidin inhibited SCF-induced p38 MAPK activation. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with KMP6 or hesperidin (P<0.05). Our results show for the first time that KMP6 potently regulates SCF-induced migration, p38 MAPK activation and inflammatory cytokines production through hindrance of SCF and c-kit binding in RPMCs. Such modulation may have functional consequences during KMP6 treatment, especially mast cell-mediated allergic inflammation disorders.
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PMID:C-kit binding properties of hesperidin (a major component of KMP6) as a potential anti-allergic agent. 2155 59

At upper gastrointestinal endoscopy to investigate unexplained diarrhea and iron deficiency anemia, duodenal biopsies are often taken to exclude a diagnosis of coeliac disease. While histology remains the gold standard for this diagnosis, recent developments in serological testing may overtake this as a first line test and biopsy restricted to confirming the diagnosis. Established coeliac disease on biopsy is straightforward, but early lesions may pose a challenge. Newer endoscopic procedures such as push-pull enteroscopy (balloon enteroscopy) with biopsy allow access to the small bowel beyond the second part of the duodenum. Controversy remains as to what constitutes the normal histology of the duodenum, and small bowel. Lymphocytic duodenosis (increased intraepithelial lymphocytes with normal villous architecture) in patients with negative coeliac serology can be associated with Helicobacter pylori, drugs, autoimmune and other diseases including food allergy. Full thickness small intestinal biopsies can aid in investigation of enteric neuropathies in severe dysmotility disorders. Biopsies are also taken to investigate malabsorption due to suspected infectious and metabolic disorders. Despite highly active anti-retroviral therapy (HAART), immunosuppressed patients may be affected by duodenal pathogens. The histology of duodenal mucosa in acid related disorders reflects the damage seen at endoscopy. Although the prevalence of duodenal ulcer disease is decreasing, drugs causing ulceration remain an important disease entity. Recent observations in functional bowel disorders suggest that the duodenum may be a key site for pathology. In functional dyspepsia, patients with early satiety may have excess eosinophil infiltration, and the mast cell is probably a key player in the irritable syndrome in the small intestine.
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PMID:Clinical value of duodenal biopsies--beyond the diagnosis of coeliac disease. 2232 33

Indolent systemic mastocytosis (SM) patients have a varied clinical presentation, ranging from predominantly cutaneous symptoms to recurrent systemic symptoms (eg, flushing, palpitations, dyspepsia, diarrhea, bone pain) that can be severe and potentially life threatening (anaphylaxis). Mastocytosis patients without skin involvement pose a diagnostic challenge; a high index of suspicion is needed in those with mast cell-degranulation symptoms, including anaphylaxis following Hymenoptera stings or other triggers. Modern-era molecular and flow-cytometric diagnostic methods are very sensitive and can detect minimal involvement of bone marrow with atypical/clonal mast cells; in some cases, full diagnostic criteria for SM are not fulfilled. An important aspect of treatment is avoidance of known symptom triggers; other treatment principles include a stepwise escalation of antimediator therapies and consideration of cytoreductive therapies for those with treatment-refractory symptoms. The perioperative management of mastocytosis patients is nontrivial; a multidisciplinary preoperative assessment, adequate premedications, and close intra- and postoperative monitoring are critical. Smoldering mastocytosis is a variant with high systemic mast cell burden. While its clinical course can be variable, there is greater potential need for cytoreductive therapies (eg, interferon-alpha, cladribine) in this setting. A systematic approach to the diagnosis and treatment of indolent SM using a case-based approach of representative clinical scenarios is presented here.
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PMID:How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). 2342 50


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