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)

Among the painters handling polyurethane varnish in two furniture manufacturing factories with high toluene diisocyanate (TDI) exposure (0.79 mg/m3 and 0.31 mg/m3), 26.3% and 15% subjects, respectively displayed asthmatic symptoms, lung function loss, and an increment in mast cell degranulation percentage specific to TDI. Some cases of TDI-linked contact dermatitis were also found among them, being elucidated by positive patch testing to TDI. However, the previous abnormalities could not be verified among the painters from another factory with TDI concentration below the TLV of it (0.11 mg/m3). It was concluded that both pulmonary hypersensitivity and contact sensitization to TDI had occurred in some of the painters included in this study, and that the immunologic effects of TDI was concentration dependent.
 ...
PMID:Immunological effects of toluene diisocyanate exposure on painters. 166 30

A cross-sectional investigation for allergology was performed of 15 painters exposed to high concentrations of toluene diisocyanate (TDI) (0.07-0.17 ppm) during the process of handling polyurethane varnish in a furniture manufacturing factory. Asthmatic reactions such as dyspnea, wheezing related to workshifts and contact dermatitis were observed in four and three cases respectively by questionnaire survey. Lung function tests on the painters showed significant decline in FEV1, %FEV1 and MMF compared to the referents. An increment in mast cell degranulation percentage could be seen in the painters. And also, patch testing with TDI were positive in five cases. From the results, it was suggested that both allergic pulmonary effects and contact sensitization had occurred in TDI-exposed painters in this factory.
 ...
PMID:Allergologic evaluation for workers exposed to toluene diisocyanate. 166 72

Inadequate reactions of the immune system, i.e. allergic or hypersensitivity reactions, may lead to lung tissue injury and possibly airway hyperreactivity. In extrinsic asthma, mast cells are considered to play a pivotal role in inducing hyperreactivity by producing various mediators. Immunoglobulin E is a well-known inducer of mast cell mediator release, and is thus often considered important. Asthma induced by a small molecular moiety such as toluene diisocyanate (TDI) is only in 15% of patients associated with increased IgE levels. TDI is a known inducer of cellular immune responses. We are investigating the relationship of type IV hypersensitivity, as an example of IgE-independent cellular hypersensitivity, with the induction of airway hyperreactivity. We have studied mice which were sensitized with picryl chloride. After antigen challenge in such sensitized mice, peribronchial and perivascular accumulation of macrophages and lymphocytes was highest 48 h after challenge. Two hours after challenge and from 7 days onwards no infiltration was found. At several time points after challenge, changes in smooth muscle tone of mouse tracheas were measured isometrically. The response to carbachol increased from 2 h after challenge, reaching a maximum 48 h after challenge and lasted for at least 3 weeks. This hyperreactivity was not found in athymic (nude) mice. We conclude from these preliminary data that airway hyperreactivity can be immunologically induced other than by IgE, and that in this model it is not associated with the presence of a mononuclear infiltrate. These experimental data indicate a potential role for T cells in inducing airway hyperreactivity, a common denominator of patients suffering from asthma.
 ...
PMID:T cell-mediated airway hyperreactivity in mice. 195 13

We quantitated serum neutrophil chemotactic activity (NCA), which is associated with mast cell or basophil activation, to determine if mast cell or basophil mediators are released during bronchoprovocation-inhalation challenge with subirritant levels of toluene diisocyanate (TDI). Four subjects with suspected TDI-induced asthma and four mite-sensitive subjects with asthma who served as a comparison group were studied. NCA was measured in a multiwell, microchemotaxis chamber. Blood samples were collected, and FEV1 measurements were performed before challenge and at regular intervals during the subsequent 24 hours. Three of four workers clinically sensitive to TDI reacted to a subirritant TDI exposure. There was no increase in NCA during placebo challenges. NCA increased in the three TDI-sensitive workers during early and late asthmatic reactions in quantities proportional to the FEV1 decline. No increase in NCA was found during TDI exposures in the TDI-negative worker. Gel filtration analysis demonstrated the main NCA fraction eluted with macromolecules of an estimated molecular weight greater than 440,000 daltons. This characteristic is compatible with neutrophil chemotactic factor of basophil or mast cell origin. The kinetics of NCA release were similar in mite- and TDI-induced asthmatic reactions. A high correlation (r = 0.97; p = 0.0006) was obtained between the percent decrease in FEV1 during early asthmatic reactions and percent increase in NCA. These observations support the hypothesis that activation of mast cells or basophils is associated with TDI-induced early and late asthmatic reaction.
 ...
PMID:Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma. 215 57

A nasal challenge model of allergic rhinitis was used to determine if pretreatment with oral theophylline reduces histamine release in vivo. Ten subjects were entered into a double-blind, cross-over trial. The results showed that both the physiologic response (sneezing) (p = 0.02) and the amount of mediators (histamine, kinins, toluene sulfonyl arginine methyl ester esterase activity) (p less than 0.01 for all) released into nasal secretions were significantly reduced after one week of pretreatment with theophylline. At the time of challenge, the serum concentrations of theophylline were between 8 and 22 micrograms/ml. It is speculated that the ability of theophylline to block the clinical response to antigen challenge and to decrease the release of mast cell mediators contributes to its clinical efficacy in the treatment of asthma.
 ...
PMID:Theophylline reduces the response to nasal challenge with antigen. 241 77

The pathogenesis of rhinitis was investigated using a model of nasal provocation with different types of stimuli. Allergic subjects had an immediate response to antigenic challenge with symptoms of rhinitis highly correlated with increments in the concentrations of histamine, prostaglandin D2, kinins and kininogens, leukotrienes, and toluene sulfonyl arginine methyl ester esterase activity in their nasal secretions. This reaction was abated by a tricyclic antihistamine also capable of inhibiting mediator release from human mast cells in vitro and, in some subjects, by disodium cromoglycate. In a number of patients, symptoms reappeared three to 12 hours after nasal provocation. This late reaction also involves release of all of the aforementioned mediators except for prostaglandin D2, and preliminary data suggest that it can be inhibited by oral or topical steroids. Cold, dry air can induce rhinitis with mast cell mediator release from selected subjects. The pathogenesis of this reaction is unclear, but there are indications that osmolarity changes are responsible for mast cell activation. Thus, mast cells can be induced to release mediators and cause nasal symptoms by both immunologic and physical mechanisms, which may account for the pathophysiology of several types of rhinitis.
 ...
PMID:Mediator release during nasal provocation. A model to investigate the pathophysiology of rhinitis. 408 96

Interrelationships between the catalytic behavior of glucose-6-phosphatase and the structure of rat-liver microsomal membranes were investigated. 2. Rabbit anti-microsomal serum completely inhibited glucose-6-phosphate hydrolysis in detergent-modified microsomes but showed no inhibitory effect on the enzyme activity of intact or mechanically disrupted vesicles. 2. Controlled proteolysis of intact microsomes using carboxypeptidase A and/or aminopeptidase M largely denatured enzymes situated on the outer surface of the microsomal vesicles such as monodehydroascorbate reductase and cytochrome c reductase. However, it did not affect the glucose-6-phosphatase activity at all, which remained in a latent state within the membrane. 3. Temperature studies on glucose-6-phosphatase have revealed that only the enzyme activity of intact microsomes exhibited a nonlinear Arrhenius plot, whereas detergent-modified microsomes showed a linear temperature response. 4. Treatment of microsomes with phospholipase C and toluene-2,4-diisocyanate resulted in an apparent loss of about 65% and 85% of the original glucose-6-phosphatase activity and was closely correlated with hydrolysis and chemical modification of phosphatidylethanolamine, respectively. These apparent inactivations could be reversed by addition of Triton X-114 alone without any phospholipid supplementation. These observations indicate that glucose-6-phosphatase is buried within the microsomal membrane, not exposed on either side. They also suggest that phospholipids are involved in the glucose-6-phosphate transport mechanism.
 ...
PMID:Investigations on the possible involvement of phospholipids in the glucose-6-phosphate transport system of rat-liver microsomal glucose-6-phosphatase. 624 79

Significant chemotactic activity for eosinophils was detected in soluble egg antigen (SEA) preparations of both Schistosoma japonicum and S. mansoni in dose-dependent fashion. The activity of S. japonicum SEA was higher than that of S. mansoni SEA. Gel filtration on Sephadex G-150 showed that S. japonicum SEA was composed of two groups of eosinophil chemotactic factors (ECFs), one of high molecular weight (JEE-H) and the other of low molecular weight (JEE-L). S. mansoni SEA showed ECF composition similar to that of S. japonicum SEA. JEE-H was stable on heating (100 degrees C, 60 min) and resistant to pronase digestion, but was sensitive to periodate oxidation. JEE-L was also stable on heating and resistant to pronase and carboxypeptidase A digestions. These properties of the ECFs were also held in common with those of S. mansoni SEA. JEE-L was extractable by toluene, indicating a hydrophobic nature. These results suggest that schistosome eggs themselves contain ECFs, and that the composition of S. mansoni and S. japonicum SEA-derived ECFs is essentially the same. However, they differ from the other ECFs which have already been described in schistosome infections.
 ...
PMID:Eosinophil chemotactic factor in schistosome eggs: a comparative study of eosinophil chemotactic factors in the eggs of Schistosoma japonicum and S. mansoni in vitro. 668 96

Fluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti-inflammatory activity which has been effectively used, intranasally, as therapy for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP has shown significant therapeutic efficacy in the management of asthma. Fluticasone propionate is a highly lipophilic molecule with good uptake, binding and retention characteristics in human lung tissue. Fluticasone propionate has high glucocorticoid receptor selectivity and affinity, demonstrating rapid receptor association and slow receptor dissociation. In vitro, FP has been shown to potently inhibit T lymphocyte proliferation, cytokine generation, tumour necrosis factor alpha (TNF-alpha)-induced adhesion molecule expression, interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate-induced mast cell proliferation, while promoting secretory leucocyte protease inhibitor production and eosinophil apoptosis. In human studies, FP has demonstrated marked vasoconstrictor potency in normal subjects and inhibited antigen-induced mucosal platelet activating factor/eicosanoid production, T lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells, with an accompanying reduction in eosinophil and mast cell markers. Clinical studies have evaluated lung function, bronchial reactivity, exacerbation rates and oral corticosteroid-sparing effect. Results show that FP has at least twice the clinical potency of beclomethasone dipropionate and budesonide. This appears to be achieved without an accompanying increase in systemic effects, suggesting a therapeutic index which may be higher than other currently available inhaled corticosteroids.
 ...
PMID:Fluticasone propionate--an update on preclinical and clinical experience. 756 73

Fluticasone propionate is a new corticosteroid based on the androstane nucleus. It is more lipophilic than beclomethasone dipropionate (BDP) and budesonide, and binds more avidly to human lung tissue. It has an absolute affinity (KD) of 0.5 nM for the glucocorticoid receptor and a relative receptor affinity 1.5- and 3.0-times greater than that of beclomethasone-17-monopropionate (17-BMP) and budesonide, respectively. The rate of association with the receptor is faster and the rate of dissociation slower than with standard corticosteroids. As a result, the half-life of the corticosteroid-receptor complex is > 10 h. Fluticasone propionate is also highly selective for the glucocorticoid receptor, with little or no activity at other steroid receptors. Pretreatment with fluticasone propionate significantly inhibits the increase in mast cell numbers in the nasal mucosa of rats chronically exposed to toluene di-isocyanate (TDI), and suppresses TDI-induced mast cell degranulation. It is more potent in vitro than dexamethasone, BDP and budesonide in inhibiting anti-CD3-induced human T-lymphocyte proliferation, in attenuating tumour necrosis factor-alpha-induced endothelial cell adhesion molecule expression, and in increasing secretory leucocyte protease inhibitor levels in airway epithelial cells. It is also more potent and longer-acting than other corticosteroids in inhibiting oedema formation, interleukin-5 (IL-5)-induced blood eosinophilia, and IL-5- or platelet activating factor-stimulated eosinophil accumulation in the lung. Fluticasone propionate therefore has increased intrinsic glucocorticoid potency and high topical anti-inflammatory activity.
 ...
PMID:The anti-inflammatory profile of fluticasone propionate. 760 48


1 2 Next >>