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)

Many classes of drugs exert anti-inflammatory activity through mechanisms which affect all or part of the inflammatory process. Some of these agents are beneficial in the practice of dermatology, while others, such as penicillamine, mast cell blockers and serotonin antagonists, find little or no application. Corticosteroids, for example, are nonspecific in their anti-inflammatory effects and remain a mainstay of therapy, despite their side effect profile. Other drugs, such as the non-steroidal anti-inflammatory agents or gold, can be used in the treatment of diseases associated with rheumatic or autoimmune states. Moreover, antihistamines play an important role in the control of itching, but are mainly indicated in controlling non-dermatological allergic sequelae. Interestingly, chloroquine and dapsone, which were originally developed for use in malaria prophylaxis and leprosy, respectively, have value in treating a wide range of dermatological conditions via mechanisms which include the inhibition of P-450 isoenzymes. In diseases characterised by disturbed cornification (e.g. psoriasis pustulosa), retinoids are of particular value. These drugs are thought to act by inhibition of collagenases, proteases and granulocyte migration. Undoubtedly, further investigation of drug classes such as oxygen radical controllers and immunomodulators will clarify their mechanisms and establish their therapeutic usefulness among the anti-inflammatory agents now available for dermatological use.
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PMID:The present status of anti-inflammatory agents in dermatology. 307 31

Twenty-one patients were entered into a phase I trial to evaluate toxicity, antitumor effects, and biological responses at tumor sites during treatment of R24, an immunoglobulin G3 (IgG3) mouse monoclonal antibody (mAb) against GD3 ganglioside. Toxicity was related to dose of R24. Urticaria and pruritus were the most prominent side effects, with nausea, vomiting, and diarrhea occurring at the highest dose levels. Partial responses were observed in four patients lasting from 6 to 46 weeks, and mixed responses were seen in two patients. Responses occurred as early as 4 weeks and as late as 10 weeks after beginning treatment. Twenty of the 21 patients developed human IgG antibodies against R24. Antimouse Ig antibodies were first detected at a median of 14 days after starting treatment, but three of the four patients who had a partial response developed the antimouse Ig responses later than 20 days. Peak serum levels of R24 were related to dose and ranged from a mean of 0.9 micrograms/mL at the lowest dose level (1 mg/m2/d) to 44 micrograms/mL at the highest dose (50 mg/m2/d). The amount of R24 reaching tumor sites corresponded to the dose administered, and R24 could be detected in tumors as late as 30 days after finishing treatment. Inflammation at tumor sites was observed during treatment. Biopsies of tumors taken before, during, and after treatment revealed that R24 induced deposition of complement components, increased numbers of mast cells with mast cell degranulation, and infiltration of T lymphocytes. These results suggest that treatment with R24 can produce a localized inflammatory response at tumor sites that is capable of producing tumor regression.
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PMID:Phase I trial of a mouse monoclonal antibody against GD3 ganglioside in patients with melanoma: induction of inflammatory responses at tumor sites. 317 29

Aquagenic pruritus is a disease in which itchy prickling skin discomfort is evoked by contact with water at any temperature without observable cutaneous lesions. Little is known about its etiology and pathogenesis. Previous reports show that increased levels of blood histamine and cutaneous mast cell degranulation are present before water exposure and that they increase still further with water challenge. This paper shows that fibrinolytic activity is markedly increased both before and after water exposure, while circulating fibrinolytic activity is normal before water exposure in three cases of aquagenic pruritus. A patient who was asymptomatic at the time of the study had no observed increase in fibrinolytic activity either before or after water challenge, suggesting that the remission of symptoms of aquagenic pruritus and normalization of cutaneous fibrinolytic activity are interdependent factors.
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PMID:Increased cutaneous fibrinolytic activity in aquagenic pruritus. 377 Oct 51

We have measured skin mast cell numbers, circulating basophils and whole blood histamine in 13 patients with polycythaemia vera. Itching was present in nine cases and correlated well with the numbers of skin mast cells but not with circulating basophils or whole blood histamine. Immediate relief of pruritus was achieved with aspirin, and myelosuppressive therapy was useful for long-term control of symptoms. Neither histamine (H1 or H2) antagonists nor iron replacement therapy were effective forms of treatment. The findings suggest that mast cell prostaglandins are an important factor in the pathogenesis of pruritus and that local vascular responses may trigger mast cell degranulation.
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PMID:Skin mast cells in polycythaemia vera: relationship to the pathogenesis and treatment of pruritus. 381 12

The efficacy, safety and mechanisms of penicillin desensitization were studied in 24 adults and two children with serious infections that required therapy with a beta-lactam drug. Indications for desensitization included debilitating as well as life-endangering infections. Increasing oral doses of phenoxymethyl penicillin were administered at 15-minute intervals to a cumulative dose of 1.3 million units. Parenteral therapy with the beta-lactam drug of choice was instituted at that point. Immunologic complications of desensitization or therapy, ranging from pruritus to serum sickness, occurred in 12 patients. The appearance of gradually worsening wheezing led to abandonment of the procedure in one subject with cystic fibrosis and severe pulmonary disease. The remaining 25 patients were successfully desensitized and received full-dose parenteral therapy. Chronic desensitization was maintained in seven individuals with twice daily oral penicillins for 3 weeks to more than 2 years. No allergic complications of chronic desensitization or recurrent full-dose parenteral therapy were detected. Skin test reactions to one or all penicillin determinants became negative in 11 of 15 patients retested after acute desensitization. Two desensitized patients became skin test negative, remained skin test negative after cessation of desensitization, and tolerated subsequent beta-lactam therapy without allergic reactions or resensitization. The results of this study provide new evidence that acute and chronic penicillin desensitization is useful and an acceptably safe approach and suggest that antigen-specific mast cell desensitization contributes to the protection against anaphylaxis.
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PMID:Acute and chronic desensitization of penicillin-allergic patients using oral penicillin. 381 32

R24 is an IgG3 mouse monoclonal antibody that identifies GD3, a prominent ganglioside on the surface of melanoma cells and other cells of neuroectodermal origin. Twelve patients with metastatic melanoma were treated with R24 at three dose levels, 8, 80, or 240 mg/m2, over a period of 2 weeks. Peak antibody levels in the serum were dose related and ranged from less than 0.1 to 62 micrograms/ml. Inflammatory reactions (urticaria, pruritus, erythema, subcutaneous ecchymoses) were observed around tumor sites in patients treated at doses greater than or equal to 80 mg/m2. Tumor biopsies during and after treatment showed lymphocyte and mast cell infiltration, mast cell degranulation, and complement deposition. Side effects were mild and were readily controlled by antihistamines. Major tumor regression has been observed in three patients.
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PMID:Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. 388 55

Forty patients with urticaria, 13 with cholinergic urticaria, 22 with urticaria factitia, and 5 with both types of urticaria, were treated with ketotifen or placebo in a double-blind crossover study. Five patients dropped out, one because of excessive weight gain. In 23 of 24 patients with urticaria factitia, ketotifen caused a marked reduction of wealing and pruritus. In contrast, only 62% of the patients with cholinergic urticaria noticed a reduction of wealing, and 69% had reduced itching. Ketotifen caused few side effects, the most frequent one being mild tiredness in 9% of the patients. The beneficial effect of ketotifen in urticaria factitia and cholinergic urticaria may be due to its ability to reduce the liberation and the effectiveness of mast cell mediators.
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PMID:[Effect of ketotifen in urticaria factitia and urticaria cholinergica in a crossover double-blind trial]. 390 13

Exercise-induced anaphylaxis (EIA) is a unique and an increasingly recognized syndrome consisting of premonitory symptoms and signs of generalized body warmth, pruritus, and erythema, which progresses on continued exertion to confluent urticaria, laryngeal edema with stridor or hoarseness, and gastrointestinal colic and frequently culminates in vascular collapse. Previous studies of five individuals with this condition have demonstrated significant elevations of serum histamine concurrent with the early clinical manifestations after experimental exercise. To assess relevant morphologic alterations in the skin of these patients, cutaneous mast cells were examined by light and transmission electron microscopy before and during the initial erythema elicited by exertion. The marked alterations observed in mast cells immediately after exercise consisted of (1) loss of electron density and internal substructure of granules, (2) fusion of granule membranes with those of adjacent granules and with mast cell membranes creating conduits to the extracellular space, and (3) an apparent decrease in the number of intact granules per cell. Biopsy specimens obtained before exercise from patients with EIA and from two normal individuals who served as control subjects were identical, and the control subjects had normal mast cell morphology after exercise. Serum histamine levels were significantly elevated in patients with EIA after exercise at the time of biopsy, whereas control subjects had normal levels. These observations provide evidence that EIA is a distinct form of physical allergy associated with mast cell degranulation similar in morphology to that of human pulmonary mast cell IgE-Fc-dependent activation secretion. Characterization of this disorder is important because its prevalence may be underestimated, and its clinical consequences, which may include some morbidity, are not fully known.
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PMID:Exercise-induced anaphylaxis: a serious form of physical allergy associated with mast cell degranulation. 398 Aug 83

We studied the relationships between dermal mast cell proliferation and pruritus or hyperparathyroidism in hemodialysis (HD). Skin biopsies were taken from 59 patients in end stage renal failure; 51 were on maintenance HD, and the other 8 were not. As a control, 34 non-renal failure pruritic patients were used. Thirty-one of the 59 end stage renal failure patients (52.5%) had pruritus. The incidences of pruritus found in patients on HD and those not on HD were 56.9% and 25%, respectively. Significantly larger numbers of dermal mast cells were found in HD patients than in the control. There was no clear relationship between dermal mast cell proliferation and serum parathyroid hormone (PTH) levels. We speculated that the cause of pruritus in the patients undergoing maintenance HD was due to an increase of dermal mast cells and a release of histamine as a result of extra-corporeal circulation.
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PMID:Pruritus and mast cell proliferation of the skin in end stage renal failure. 402 25

Exercise-related anaphylaxis is a novel form of physical allergy that is being recognized with increasing frequency in a society with a growing commitment to health through planned exercise. The clinical manifestations progress from pruritus, erythema, and urticaria to some combination of cutaneous angioedema, gastrointestinal and laryngeal symptoms and signs of angioedema, and vascular collapse. The finding of an elevated serum histamine level during experimentally-induced attenuated attacks indicates mast cell participation, as in a physical allergy, and the signs and symptoms are characteristic of a classic anaphylactic reaction to a foreign substance in an allergic human.
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PMID:Exercise-induced anaphylaxis. 671 33


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