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)

We evaluated basophil releasability in two groups of allergic patients with positive skin tests to Dermatophagoides pteronyssinus major allergen (Der p l) (29 adults with bronchial asthma and 17 with allergic rhinitis) and in 31 age-matched normal donors. Both basophil reactivity (maximal percent histamine release) and basophil sensitivity (the concentration that causes 50% of maximal percent histamine release: HC50) to Der p l in patients with asthma were similar to those in patients with allergic rhinitis. On the contrary, basophil reactivity to anti-IgE was significantly higher in patients with asthma (58.0 +/- 3.6%) than in patients with allergic rhinitis (46.3 +/- 5.2%; p less than 0.05). Both groups of patients showed an increased releasability compared to control subjects (27.3 +/- 4.6%; p less than 0.001), whereas there were no significant differences in basophil sensitivity to anti-IgE among the three groups of donors. Differences were also found with respect to basophil reactivity and sensitivity to f-met peptide, whereas no differences appeared when basophils from the three groups of donors were challenged with the Ca2+ ionophore A23187. There was a significant correlation between basophil reactivity and sensitivity to Der p l and to anti-IgE in both asthmatic and allergic rhinitis patients. A significant correlation was found between basophil reactivity and sensitivity to anti-IgE and serum IgE level only in patients with bronchial asthma, whereas no correlations were found in patients with allergic rhinitis. There was no correlation between in vivo mast cell releasability and in vitro basophil releasability in response to Der p l in either group of allergic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Human basophil releasability. VI. Changes in basophil releasability in patients with allergic rhinitis or bronchial asthma. 170 Jun 53

Food allergy (FA) is a very important problem affecting numbers of infants and children with protean manifestations which are frequent challenges to the pediatrician and other specialists working with children. Adverse reactions to food are very complex, frequently mediated bu IgE mechanisms, and often by other mechanisms. To make the correct diagnosis and to arrive at a proper therapeutic approach requires all the skill a physician can gather. Only an extensive knowledge of the various mechanisms and pharmacologic agents that can be used to prevent or treat these adverse reactions will allow the physician to approach the problem scientifically and come to a reasonable solution for the patient. The role of dietary factors in atopic dermatitis (AD) has long been a subject of controversies. However, it has been shown that FA plays a role in some children with AD. Therefore, the management of this multifaceted disorder is a challenge for pediatricians, dermatologists, and allergists. SCG, which is the salt of a bis-chromone carboxylic acid, has been shown to be of proven efficacy in the prophylaxis of bronchial asthma, allergic rhinitis, and of other disorders associated with mast cell degranulation. The drug has different modes of action, such as inhibition of rat passive cutaneous anaphylaxis, and the antigen-induced histamine release from passively sensitized peritoneal cells. Recently, clinical studies indicated that SCG has a direct effect on inflammatory cells, inhibiting either various leukocyte functions (membrane receptor expression, cytotoxic capacity), or "in vitro" activation of human neutrophils, eosinophils and monocytes. Although SCG has been widely used for the management of respiratory allergy, conflicting results of FA treatment have been reported by several authors. We have reviewed 18 papers on the use of SCG in the management of children with FA, which included 341 children aged 0.5-15 years. In this paper we discuss 12 studies reporting 281 children affected with AD.
 ...
PMID:Food allergy in children: diagnosis and treatment with sodium cromoglycate. 170 97

Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria-induced mediator release from superficially lying cells in the airways epithelium might be of importance for the precipitation or exacerbation of bronchial asthma in respiratory tract infections.
 ...
PMID:Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes. 170 12

Astemizole (0.5-5 mg/kg, p.o.) dose-dependently inhibited heterologous and homologous PCA reactions in rats at ID50 values of 1.48 mg/kg and 2.37 mg/kg, respectively. The inhibitory effect of astemizole on heterologous PCA was most remarkable when this compound was given p.o. 2 h prior to antigen challenge. Astemizole (0.1-5 mg/kg, p.o.) dose-dependently inhibited experimentally-induced asthma in guinea pigs at an ID50 of 0.86 mg/kg. Ex vivo, astemizole (0.5-5 mg/kg, p.o.) inhibited antigen-induced histamine release from lung pieces of sensitized guinea pigs. In in vitro experiments, the drug dose-dependently inhibited antigen-induced histamine and SRS-A releases from guinea pig lung pieces at concentrations of 0.05-10 microM. Furthermore, astemizole (0.1-10 microM) inhibited the histamine release induced by compound 48/80 and antigen-antibody reaction from rat peritoneal mast cells, and at 0.1-500 nM inhibited both leukotriene C4- and platelet-activating factor (PAF)-induced contraction of isolated guinea pig trachea at submicromolar concentrations. Astemizole not only inhibited 45Ca uptake into rat mast cells but also prevented the Ca2+ release from the intracellular Ca store induced by compound 48/80, although this compound did not affect the histamine release from permeabilized mast cells induced by Ca2+. Our results suggest that one of the antiallergic mechanisms of astemizole may be an inhibition of signal transduction from the mast cell membrane to the intracellular systems.
 ...
PMID:Antiallergic effects of astemizole on immediate type hypersensitivity reactions. 170 34

To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.
 ...
PMID:Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. 171 32

IgG autoanti-IgE is detectable in a large proportion of individuals with allergic asthma, where it is suggested to be potentially involved in modulating IgE-mediated hypersensitivity. Using a series of overlapping recombinant human epsilon-chain peptides, we have shown that circulating IgG anti-IgE antibodies recognise at least 2 epitopes located within the C epsilon 2 and the C epsilon 4 domains, respectively. The C epsilon 2 recognition site is located within the C-terminal portion of the C epsilon 2 domain (i.e. aa301-339) which is thought to contribute residues to the Fc epsilon RI-binding site on IgE. The recognition by autoanti-IgE of an effector function site of such pivotal importance in IgE-mediated hypersensitivity suggests that it plays a possible modulatory role during mast cell and basophil activation.
 ...
PMID:Elucidation of the epitope locations of human autoanti-IgE: recognition of two epitopes located within the C epsilon 2 and the C epsilon 4 domains. 171 4

From current information, a number of conclusions can be drawn. Antigen activation of the allergic reaction in the airways is associated with an immediate rise in mast cell derived mediators, including histamine and tryptase. Associated with antigen activation of the allergic reaction is recruitment of eosinophils to the airways. This can best be seen in the airway lavage 48 hours after challenge with antigen. An increased presence of eosinophils suggests that they are an important contributor to the late allergic reaction and may be one of the major constituents in the development of bronchial inflammation. Although many factors participate in the late allergic inflammatory response, eosinophil-derived proteins are known to cause airway injury. Regulation of eosinophils in this process is not clearly established; however, our findings of increased IL-5 in relationship to the presence of eosinophils and their granular proteins suggests that this cytokine may be an important modulator of eosinophil function and activation following allergen challenge. However, much remains unknown in understanding bronchial inflammation and the eosinophil's role in the process. In conclusion, the eosinophil is a major cellular participant in late phase allergic airway disease. Its presence and known functions suggest that the eosinophil is a significant cellular factor in the development of allergic airways disease in asthma. Further advances in this area will follow continued studies, particularly those which involve biopsy and correlation with airway physiology.
 ...
PMID:The role of eosinophils in the pathophysiology of asthma. 171 54

The involvement of mast cells in the pathogenesis of aspirin (ASA)-induced respiratory reactions was investigated by measuring serum levels of tryptase, a neutral protease that is a specific marker of mast cell activation. ASA challenges were performed in 17 ASA-sensitive patients with asthma and rhinosinusitis, and tryptase and histamine levels were measured in their venous blood samples. In three subjects who experienced moderate to severe respiratory reactions extending to the skin and/or gastrointestinal tract, marked elevations of tryptase levels in postreaction serum samples (peak levels, 51.9 and 40.0 ng/ml) were discovered in two of these three subjects, and a small elevation of tryptase occurred in the serum of the third subject (3.1 ng/ml peak). Plasma histamine levels in postreaction samples were significantly elevated over baseline values in all three subjects (delta mean plasma histamine, 238 pg/ml versus 56 pg/ml for the remaining 14 subjects; p less than 0.04). In the remaining 14 subjects, who experienced similar respiratory reactions without extrapulmonary symptoms during aspirin challenge, changes in tryptase and histamine levels were not observed.
 ...
PMID:Tryptase and histamine release during aspirin-induced respiratory reactions. 172 Jul 95

Exercise-induced asthma (EIA) may affect up to 90% of patients with asthma. Hyperpnea associated with exercise leads to increased airway water and heat loss, which contributes to the development of EIA. Measurement of circulating mediators has suggested that mast cells may participate in the development of EIA via release of histamine and neutrophil chemotactic factor. To evaluate further the contribution of pulmonary mast cell-mediator release in the pathogenesis of EIA and to determine whether EIA is associated with enhancement of airway inflammation, we studied 11 subjects with mild stable asthma (FEV1, 93% +/- 3% predicted; mean +/- SEM) with significant EIA (after exercise fall in FEV1, 41% +/- 5%). Bronchoalveolar lavage (BAL) was performed immediately (less than 1 hour) after exercise challenge (EC) and repeated 24 hours later (exercise studies). On another occasion, paired BALs were done 24 hours apart (control studies). A minimum of 2 weeks separated the exercise and control pairs. No changes were observed in BAL cell counts, differentials, or reactive oxygen species metabolism after EC. Neither BAL histamine nor BAL tryptase levels increased, either shortly (less than 1 hour) or 24 hours after EC. We conclude that EC in subjects with asthma is not associated with cellular influx to airspace and that mechanisms other than histamine release by pulmonary mast cells may be responsible for EIA.
 ...
PMID:Exercise-induced asthma is not associated with mast cell activation or airway inflammation. 173 Aug 41

Asthma is characterized by airway inflammation and hyper-responsiveness. Clinically, these features are manifested by attacks of cough, wheezing, and dyspnoea. Nocturnal asthma symptoms are frequent; 39% of asthmatics awaken nightly, and 94% have nocturnal awakenings at least once a month. A number of mechanisms have been hypothesized to explain the phenomenon of nocturnal asthma, including exposure to dust mite allergen, late-phase allergic reactions, effects of posture and sleep stage on airway tone, gastro-oesophageal reflex, impaired mucociliary clearance, airway cooling, and changes in circadian rhythms of circulating hormones. While no single mechanism can explain these changes, circadian rhythms may be particularly relevant. Normal airway tone increases during sleep and is magnified in asthmatics. Bronchial responsiveness to histamine and allergen challenge increases during sleep and mast cell mediator release is enhanced. Circulating eosinophils increase, which may allow their ingress into pulmonary tissue. Decreases in plasma catecholamine and cortisol levels have also been observed. All of these may influence airway tone, inflammation, and responsiveness during sleep and produce the observed clinical picture. Inhaled sympathomimetics are frequently ineffective in preventing nocturnal symptoms due to their short duration of action. While corticosteroids, cromoglycate, and anticholinergics are effective, sustained-release theophylline is particularly advantageous for controlling nocturnal symptoms. Once-daily theophylline when dosed in the evening not only controls nocturnal symptoms and improves airflow during the early morning hours, but decreases airway responsiveness to histamine as well. The close association between airway inflammation, airway hyper-responsiveness, and nocturnal asthma symptoms makes further studies of the mechanism of action of theophylline especially interesting.
 ...
PMID:Nocturnal asthma: mechanisms and the role of theophylline in treatment. 175 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>