Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine released from skin mast cells in normal skin sites of patients with idiopathic chronic urticaria (CU) and normal volunteers was assessed with the skin chamber technique. Small amounts of histamine were spontaneously and continuously released during the 4-hour observation in both groups but were twofold greater in patients with CU. In addition, histamine levels were significantly more elevated in sites challenged with compound 48/80 than in unstimulated sites. Patients with CU differed from normal volunteers in that histamine release induced by 48/80 compound was significantly greater at 1 and 2 hours after challenge. The number of mast cells and the histamine content of the skin did not differ in the two groups. These observations could suggest a functional defect at the mast cell level rather than a difference in their numbers.
 ...
PMID:Increased compound 48/80 induced local histamine release from nonlesional skin of patients with chronic urticaria. 243 Oct 27

Profiles of histamine release by nonlesional skin mast cells from patients with chronic urticaria (CU) and normal control (NC) subjects were compared on stimulation with a wide range of concentrations of compound 48/80 (0.15 to 4.8 mg/ml). One previous observation demonstrating spontaneous and 48/80-induced release of histamine greater in patients with CU than in NC subjects was confirmed with a concentration of 48/80 believed to produce mast cell activation in most subjects (2.4 mg/ml). In fact, higher concentrations of histamine were released by patients with CU than by NC subjects on stimulation with 48/80 at concentration greater than 0.6 mg/ml. With 0.6 mg/ml of 48/80, the profiles of histamine release were comparable in the two groups, and for concentration less than 0.6 mg/ml, the profiles of release were completely different, being higher in NC subjects than in the group with CU. The peak histamine response was higher in the group of NC subjects (6500 pg/ml) than in the group with CU (5100 pg/ml), and the concentration of 48/80 needed to trigger maximum release was lower in the NC subjects than in the subjects with CU (0.15 versus 0.6 mg/ml). The production of leukotriene B4 and leukotriene C4 was also compared in these two groups after stimulation with 2.4 mg/ml of compound 48/80. No significant amount of leukotriene B4 was found in the collection chambers, but small amounts of leukotriene C4 were measured into skin chamber fluids during a period of 4 hours. No significant difference could then be observed between the two groups.
 ...
PMID:Analysis of compound 48/80-induced skin histamine release and leukotriene production in chronic urticaria. 245 74

Basophil leukocytes and tissue mast cells are inflammatory cells that are found in virtually all human tissues. They appear to be involved in the pathogenesis of such allergic diseases as allergic rhinitis, bronchial asthma, anaphylaxis, atopic and contact dermatitis, chronic urticaria, and hypersensitivity pneumonitis. By releasing a variety of chemical mediators, they could also play a role in the pathophysiology of a wide range of inflammatory disorders of the joints, and of intestine, lung, coronary, and myocardial diseases. Although these two cell types are similar in several aspects, striking differences have also been observed. Moreover, human mast cells from different anatomical sites and within an individual tissue synthesize different mediators and have different release mechanisms. The recent advent of techniques that yield highly purified basophils and mast cells from diverse tissues will probably lead to major advancements in understanding the biochemical and pharmacological mechanisms that control the release process of these cells. The release of mediators from these cells is also controlled by a series of largely undefined biochemical steps that represent the basis of the concept of basophil and mast cell releasability. Alterations of basophil or mast cell releasability have already been detected in patients with allergic rhinitis, bronchial asthma, atopic dermatitis, and chronic urticaria. Taken together, these findings demonstrate that basophils, mast cells, and their chemical mediators play a pivotal role in several inflammatory disorders.
 ...
PMID:Pathophysiology of human basophils and mast cells in allergic disorders. 246 27

Despite the suggestion than an intolerance reaction could be a possible cause of chronic urticaria in some cases, the pathogenesis of this disease remains enigmatic. It is unlikely that an intolerance reaction to substances used in provocation testing is the cause of the daily rashes. It rather seems that the intolerance reaction is an indication of a certain instability of the mast cell membrane of other factors of the reaction cascade leading to the wheals. Fortunately, an effective symptomatic therapy is available in such cases where the cause cannot be detected and the trigger cannot be avoided. The modern, non-sedating H1-antihistamines have been tested in clinical-experimental studies as well as in a multicentric study in patients with chronic urticaria. In histamine-induced wheals, terfenadine was slightly superior to other non-sedating H1-blockers, when the grade of reduction of wheals and flare areas was taken as criterion. In clinical studies, another antihistamine, loratadine, was slightly, but statistically not significantly superior to terfenadine. In cases that cannot be effectively treated with H1-blockers alone, the additional administration of non-steroidal antiphlogistics (acetylsalicylic acid, indomethacin) is recommended. To avoid aggravation of the symptoms caused by the antiphlogistics, the drugs must be given in increasing dosages and after concurrent treatment with H1-blockers. With this combined therapy, about 50% of the patients present amelioration.
 ...
PMID:[Chronic urticaria--still a vexing problem? Progress in diagnosis and therapy]. 290 90

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.
 ...
PMID:Skin reactions to histamine and compound 48/80 in chronic urticaria: a diagnostic tool? 338 11

Oxatomide is an orally active H1-histamine receptor antagonist which, as appears to occur with some other antihistamines, also inhibits mast cell degranulation. Oxatomide has demonstrated response rates similar to those with other more established members of its drug class in a few studies of chronic urticaria and allergic rhinitis. Interestingly, some patients responding to oxatomide were said to be unresponsive to previously administered antihistamines. The effect of oxatomide was little different from placebo in clinical trials of bronchial asthma in adults. While somewhat more encouraging results have been reported in children with bronchial asthma when higher than presently recommended dosages were employed, and in follicular conjunctivitis, atopic dermatitis and food allergy, reports to date are largely preliminary in nature and additional well-controlled studies are needed to clarify the efficacy of oxatomide in such conditions. The drug has been generally well tolerated, but shares some of the familiar H1-histamine receptor antagonist side effects. As with other similarly acting drugs, the 2 primary side effects with oxatomide are drowsiness and weight gain. Thus, on the basis of present evidence, a trial with oxatomide seems a potentially useful alternative in patients with conditions known or thought to be allergic in nature, in whom more established treatments were ineffective or poorly tolerated.
 ...
PMID:Oxatomide. A review of its pharmacodynamic properties and therapeutic efficacy. 620 Feb 90

Skin biopsy specimens were obtained from 43 consecutive patients with chronic idiopathic urticaria and from seven normal controls. Of 43 patients, 42 had a non-necrotizing perivascular infiltrate composed primarily of mononuclear cells. There was no evidence of damage to vessel walls, of nuclear debris, or of extravasation of red blood cells, and most cells were seen around vessels rather than within the vessel wall. One patient had vasculitis with a neutrophilic infiltrate, nuclear debris, and positive immunofluorescence. Quantitative cell counts revealed four times the number of mononuclear cells and 10 times the number of mast cells in urticaria biopsy sites vs normal skin. Thus chronic urticaria is characterized by an accumulation of mononuclear cells and mast cells with mast cell degranulation presumably associated with hive formation. In our series, the characteristic lesion is not vasculitic. The stimulus responsible for the infiltration of skin with these cells is unknown.
 ...
PMID:Histologic studies of chronic idiopathic urticaria. 682 93

Early wheal responses to intracutaneous codeine injection have virtually no tendency to proceed to late cutaneous responses in normal subjects and patients with chronic urticaria. This finding is taken to indicate that the transient burst of mast cell mediator release/activation in a quantity sufficient to elicit a sizable early response may not, by itself, fulfill conditions required to lead to late cutaneous allergic responses. In patients with angioedema and a recent requirement for steroid therapy early wheals followed by small late cutaneous responses were elicited by codeine and histamine. This effect by histamine, not observed in normals, indicates a unique host susceptibility to prolonged responses in these individuals. The inhibition of these small late responses by ingested prednisone may be representative of the mechanism of therapeutic efficacy of the drug in these cases.
 ...
PMID:Does non-immunologic mast cell mediator release/activation elicit a late cutaneous response? 683 21

Chronic urticaria can be produced by a number of stimuli that cause mast cell mediator release. Patients with urticaria caused by physical agents account for roughly one-fifth of all cases of chronic urticaria. There are about 20 different types of physical urticaria. Two forms, dermographism and cholinergic urticaria, are quite common and represent more than two-thirds of all cases of physically caused urticaria. More than one agent may precipitate urticaria in a given individual. Urticarial response can be easily reproduced in the sensitive patient and, generally, lasts less than one hour. Systemic features such as flushing, dizziness, headaches, and even hypotension, may occur during severe episodes. Identification of the causative physical agent is necessary for effective therapy.
 ...
PMID:Physical urticarias. 817 38

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.
 ...
PMID:Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria. 861 29


<< Previous 1 2 3 4 5 6 7 8 9 Next >>