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

To determine the efficacy of the mast cell-stabilizing drug ketotifen in scleroderma, we conducted a 6-month, randomized, prospective, double-blind, placebo-controlled trial in 24 patients. No significant improvement in the clinical parameters, pulmonary function, global assessments, and mast cell releasability was noted. Pruritus tended to improve in the group taking the active drug. Six months of treatment with ketotifen (6 mg/day), therefore, produced no apparent benefit in patients with early scleroderma. We were unable to address the role of mast cells in scleroderma since mast cell suppression was not achieved.
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PMID:A double-blind randomized controlled trial of ketotifen versus placebo in early diffuse scleroderma. 200 58

The significance of the mast cell in the pathogenesis of rheumatic diseases continues to receive attention. Increased numbers of mast cells are found in the synovial tissue and fluid of patients with inflammatory arthritides, and these mast cells can be activated by many of the substances found in inflammatory synovial fluid. This activation results in the release of mediators that are capable of amplifying the inflammatory process within the joint space. Recent research has shown that mast cells also produce a variety of cytokines and hematopoietic growth factors that may have paracrine and autocrine functions that are important to the development of the inflammatory cell infiltrate. Increased numbers of mast cells are also found in many fibrotic conditions, including scleroderma. These mast cells, directly or through mediator generation, affect the function of endothelial cells, fibroblasts, and growth factors important to the proliferation and function of these cells. A clearer understanding of mast cell involvement in the inflammatory arthritides and fibrotic processes should lead to new therapeutic strategies.
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PMID:Arthritis and mast cell activation. 222 35

Paired biopsy samples from involved and uninvolved skin were obtained from 19 patients with generalized scleroderma (11 with early, progressive disease and 8 with late, improving disease). Skin biopsy samples were double stained for mast cell granules and for mast cell membrane. The number of mast cells was increased in patients with systemic sclerosis (SSc), in both involved and uninvolved skin and in both early and late disease. There was an increase in the number of degranulated mast cells in the involved skin of patients with both early and late disease and in the not-yet-involved skin of patients with early disease; however, there was no increase in the number of degranulated mast cells in areas of previously involved but now normal skin of patients with late disease. Increases in mast cell number and degranulation precede clinically apparent dermal fibrosis in SSc. These observations and the absence of mast cell degranulation in regressing skin suggest a participatory role of the mast cell in the clinical progression of skin changes in SSc.
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PMID:Dermal mast cell degranulation in systemic sclerosis. 224 67

Mast cells in the skin of the tight-skin mouse show an enhanced degranulation compared to those of syngeneic litter mates. Oral treatment with ketotifen, an inhibitor of mast cell degranulation, at a dose comparable to that recommended for man, was associated with a decrease in both mast cell degranulation and in skin fibrosis, suggesting the potential for its use in human scleroderma.
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PMID:Ketotifen prevents skin fibrosis in the tight skin mouse. 231 74

Mast cells are being recognized as important constituents in fibrotic processes. This article reviews the evidence for increased mast cell numbers and/or function in a variety of fibrotic conditions. Increased mast cell numbers and activity are seen in chronic murine graft-versus-host disease (a model for scleroderma) and in active scleroderma itself. An integrated schema for scleroderma is presented, emphasizing the interactions among mast cells, endothelial cells, and fibroblasts mediated by heparin and heparin-binding growth factors.
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PMID:Mast cells and fibrosis. The relevance to scleroderma. 240 4

Over the years, many encouraging uncontrolled studies extolling treatments of SSc have appeared, but initial impressions were not corroborated when controlled trials were done. This article points out that certain recent studies have effectively ruled out the use of some specific therapies for the general treatment of systemic sclerosis. Thus, sufficient data has been generated to rule out the use of n-acetylcysteine, colchicine, chlorambucil, cyclofenil, and DMSO, at least in disease of longer duration. Ketanserin and prostaglandin infusions probably also belong in this group, as they affect only Raynaud's phenomenon. Angiotensin enzyme inhibitors, while probably life-saving in renal crises, do not seem to affect the underlying systemic sclerosis per se. Another group of drugs has only limited supportive data and await well-controlled trials to prove or disprove their effectiveness. These include: 5-fluorouracil, D-penicillamine, drugs affecting platelet function (dipyridamole), and para-aminobenzoic acid. There are a few treatments which have potential. Factor XIII has only limited data using controlled trials, but what does exist seems positive. Apheresis is encouraging, although the success of this treatment modality may be dependent upon a "combination" approach. Ongoing studies with gamma-interferon, photopheresis, and the mast cell stabilizer ketotifen appear exciting, and we await reports of their use in scleroderma. On another level, new insights into genomic alterations in skin fibroblasts and T-cell proto-oncogene expression have contributed to the understanding of the pathogenesis of this disease at the cellular level and new methods to measure change in disease will help gauge response to therapy. Thus, we look forward to more definitive treatment of SSc in the future.
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PMID:Treatment of generalized systemic sclerosis. 240 9

To investigate the role of mast cells and cell-mediated immunity in the pathogenesis of scleroderma, we studied wheal size after skin testing with compound 48/80, a liberator of mast cell histamine, and demonstrated increased mast cell releasability in skin that appeared normal, adjacent to involved skin. Immunofluorescent staining for HLA-DR showed dermal positivity in 12 of 13 involved- and 9 of 13 uninvolved-skin biopsy specimens from scleroderma patients, compared with only 1 of 10 controls. By immunoperoxidase staining, most of the DR positivity was found in fibroblast-like cells. These findings further support the notion of immunologic dysfunction in scleroderma.
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PMID:Immunologic dysfunction in scleroderma: evidence for increased mast cell releasability and HLA-DR positivity in the dermis. 245 20

An integrated view of the pathogenesis of scleroderma should include vascular, immunologic, and fibrotic processes. This review introduces the mast cell into this picture, emphasizing recent knowledge gained from a study of experimental chronic graft-vs-host disease and scleroderma itself. In both of these situations, increased mast cell activity occurs. A link between the activation of both endothelial cells and fibroblasts may be provided by the family of heparin-binding growth factors. These cytokines are produced by many cells and are bound, protected, and enhanced by heparin, which may be provided by the activated mast cells. These and other growth factors may be responsible for endothelial proliferation and excess collagen production by fibroblasts. This enlarged schema should provide additional points for therapeutic intervention in scleroderma.
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PMID:On scleroderma. Mast cells, endothelial cells, and fibroblasts. 229 59

A 63-year-old woman had rapidly progressive scleroderma and died 4 months after the clinical appearance of her illness. Extreme itching of the affected skin was prominent. Electron microscopic study of the clinically uninvolved skin showed mainly normal mast cells. Mast cells in clinically involved skin showed a wide morphologic spectrum including evidence of cellular activation. There was an increased amount of cytoplasm occupied by polysomes and mitochondria and less cytoplasm occupied by granules. Most granules were pale and swollen, suggesting active degranulation. In some cases it was difficult to distinguish a hyperactive mast cell with only a few granules remaining from a fibroblast which had acquired granules by transgranulation. This case illustrates the active participation of mast cells in acute scleroderma.
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PMID:Mast cell changes in a case of rapidly progressive scleroderma-ultrastructural analysis. 291 35


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