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)

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by bronchial colonization with Aspergillus fumigatus that affects approximately 10% of patients with cystic fibrosis (CF). The diagnosis in CF patients is difficult because the cardinal symptoms of ABPA occur frequently in CF, ie, pulmonary infiltrates and wheezing, as well as the frequent colonization with A fumigatus that leads to humoral reactivity. If left untreated, ABPA leads to bronchiectasis and pulmonary fibrosis. The pathogenesis of ABPA seems to be a prolonged asthmatic late-phase reaction orchestrated by CD4+ Th2-like T cells in response to persistent pulmonary A fumigatus allergen exposure. Thus, polyclonal and A fumigatus-specific IgE antibodies (and IgA and IgG) and blood pulmonary eosinophilia are stimulated by Th2-derived cytokines such as IL-4 and IL-5. In addition, IL-4 would also promote pulmonary transendothelial migration of eosinophils, basophils, and lymphocytes via induction of cell adhesion molecules and their ligands. IgE mast cell interactions would also contribute to the bronchial reactivity and inflammation. Recent advances have begun to identify immunodominant A fumigatus allergens. Evaluation of the quantity of IgE antibodies (and IgA and IgG) and T-cell cytokine responses to specific A fumigatus allergens should aid in the diagnosis and immunopathogenesis of ABPA, especially in CF patients.
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PMID:Allergic bronchopulmonary mycosis complicating cystic fibrosis. 147 42

Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research.
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PMID:Precipitating factors of asthma. 161 89

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.
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PMID:Allergologic evaluation for workers exposed to toluene diisocyanate. 166 72

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.
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PMID:Nocturnal asthma: mechanisms and the role of theophylline in treatment. 175 31

Investigators have tried to develop various experimental preparations suitable to study the effects of antigen on skin and airways in order to understand the mechanisms involved in asthma and to develop new methods of diagnosis, prevention and treatment. We have gained considerable experience in studies of specific antigens in inbred dogs with increased levels of serum IgE antibodies to aeroallergens. By using a new method of sensitization, combining an attenuated live virus with a specific and potent antigen, we have developed an experimental preparation that has many features resembling human asthma: High serum levels of IgE antibodies were specifically directed against ragweed antigen. Skin and airway responses to antigen were specific and reproducible. Airway responsiveness to histamine and methacholine aerosols was significantly increased in immunized dogs. Similar to human asthma, ragweed-induced bronchoconstriction in ragweed-sensitized dogs was severe and associated with profound abnormalities in cardiopulmonary function and appeared to be of greater magnitude than usually seen in Ascaris-induced reactions. Ragweed-sensitized dogs had atopic dermatitis, particularly during grass pollen season, confirmed by biopsy and described previously in atopic dogs. Ragweed-sensitized dogs did not have spontaneous wheezing, but usually had diffuse, severe wheezing during induction of anesthesia; cardiac arrhythmias were also common during anesthesia. Ragweed-sensitized dogs appeared to differ from Ascaris-sensitive dogs with respect to skin responsiveness. There was a surprisingly narrow range of skin responsiveness to antigen, whereas Snapper et al. in 1980 reported a wide range of skin responsiveness to Ascaris suum antigen in a group of mongrel dogs. Skin responsiveness to histamine was greater in ragweed-sensitized dogs than in nonimmunized dogs. Similar to human atopic patients, we found frequent late-phase reactions to ragweed antigen. As described below, we showed that antigen-induced mast cell degranulation in skin and airways was associated with inflammation which, in turn, was associated with increased airway responsiveness to pharmacologic agents. The generation of thromboxane by inflammatory cells induced by antigen challenge in ragweed-sensitized dogs appears to play a critical role in altering the response of both airways and skin to pharmacologic agonists.
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PMID:Mechanisms of antigen-induced reactions in skin and lung. 349 83

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

Nocturnal asthma is a common and troublesome problem. Many possible mechanisms have been proposed, including exposure to allergens, sleep itself, the supine posture, withdrawal of bronchodilator drugs, gastric reflux, mucus plugging, and airway cooling. Although these may be contributory factors in individual patients, they cannot provide a universal explanation for the phenomenon of nocturnal and early morning wheezing. It now seems that nocturnal asthma may best be understood in terms of circadian rhythms. A circadian variation in airway caliber has been demonstrated in normal subjects; in asthmatic subjects, the same rhythm is present but with greater amplitude. The amplitude is magnified by bronchial hyper-responsiveness, a cardinal feature of asthma. Evidence now suggests that the fall in circulating epinephrine level at night removes an important defense against bronchoconstriction in asthmatic subjects, and this itself may be magnified by removal of the braking effect of epinephrine on mast cell mediator release. In addition, increased vagal reflex bronchoconstriction and the delayed effects of the fall in plasma cortisol level may also contribute to nocturnal wheezing. Thus, nocturnal asthma may be explained by a complex interaction of several coincident circadian rhythms, which produce only small changes in airway caliber in normal subjects; however, in asthmatic patients, these constrictor effects are magnified to produce bronchospasm severe enough to wake the patient.
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PMID:Circadian variation in airway function. 408 99

Mast cells occur throughout most tissues although they are more prevalent in areas which come into contact with the external environment such as the skin, lungs, and gastrointestinal tract. The physiologic role of this cell is not known; however, it has a recognized pathophysiologic role as an effector cell in immediate hypersensitivity reactions. Such mast cells, when activated by either immunologic or non-immunologic stimuli, both release and generate chemical mediators such as histamine and leukotrienes which then act on surrounding tissues. Depending upon the site of mast cell degranulation, a variety of clinical findings ensue. For example, mast cell degranulation in the lungs may lead to wheezing, while mast cell degranulation in the gastrointestinal tract may lead to vomiting and diarrhea. It is now recognized that not all mast cells are identical. The best example of this mast cell heterogeneity is found in the gastrointestinal tract. There is evidence that certain gastrointestinal mast cells both contain and generate mediators either distinct from or differing in quantity from those of mast cells found at other sites. Such observations suggest that a knowledge of these differences is required to understand gastrointestinal diseases in which mast cell activation plays a part.
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PMID:Mast cell mediators with emphasis on intestinal mast cells. 609 3

Infection of airway epithelial cells with respiratory syncytial virus (RSV) results in the production of a restricted number of cytokines, which may modulate the inflammatory response to infection. To get a better understanding of epithelial cell-mediated inflammatory processes in RSV disease, the aim of the present study was to identify the production of mononuclear cell/eosinophil/mast cell inflammatory chemokines [monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein-1beta, and RANTES] during productive RSV infection in airway epithelial cells. Normal human primary bronchial epithelial cell cultures, nasal epithelial cell explants, and the BEAS-2B airway epithelial cell line were inoculated with RSV, and chemokine induction was assessed during the phase of logarithmic increase in infectious virus production. Only RANTES was found to increase in epithelial cell cultures in an infection-dependent manner. Furthermore, RANTES was released only by RSV-producing cells. To determine whether RANTES was induced by RSV infection in vivo, RANTES was measured in nasal lavage fluids (NLF) from children with RSV-positive and RSV-negative upper respiratory infection and children when they were well. RANTES was increased significantly during RSV infection (128 +/- 38 pg/ml NFL) compared with non-RSV infection (42 +/- 12 pg/ml NFL) and with asymptomatic baseline (13 +/- 4 ng/ml NFL) in the same children. Because RANTES is an effective eosinophil and memory T cell chemoattractant and activator and because eosinophil-dominated inflammation is a hallmark of asthmatic airways, RANTES may play a role in the pathogenesis of RSV-induced exacerbations of airway reactivity and wheezing.
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PMID:RSV infection of human airway epithelial cells causes production of the beta-chemokine RANTES. 912 9

Respiratory infections are common causes of increased asthma for patients of all ages. Current evidence indicates that viral, and not bacterial, infections are the most important respiratory illnesses which increase the severity of asthma. Of the respiratory viral infections associated with increased asthma, rhinoviruses, i.e. the cause of common colds, have proven to be the virus most often found in association with increased asthma severity. Although the association between rhinovirus infections and asthma is most dramatically illustrated in children, asthma patients of all ages can be affected and the attacks of asthma can be severe. Studies to establish the mechanisms by which rhinoviruses enhance asthma severity have begun to focus on how this virus promotes allergic inflammation. We have found that experimental rhinovirus infections enhance airway responsiveness and, perhaps most importantly, the likelihood that a late allergic reaction will occur to an antigen challenge. Furthermore, using bronchoscopy and segmental antigen challenge, we have found that rhinovirus infections promote mast cell release of histamine and the recruitment of eosinophils to the airways. These data support the concept that rhinovirus infections act to promote allergic inflammation and by this mechanism increase both the likelihood of asthma occurring and the severity of wheezing.
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PMID:The role of respiratory viruses in asthma. 925 14


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