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)

A plethora of drugs is available for the treatment of ocular allergy. Traditional treatment includes antihistamine and antihistamine/vasoconstrictor combination eyedrops. These drugs are useful, safe, and readily available. Mast cell stabilizers are safe, effective, and an important component of antiallergic therapy. Nonsteroidal anti-inflammatory drugs also have antiallergic effects. In recent years, drugs with multiple mechanisms of action have proven to be effective antiallergics. These drugs often have mast cell stabilizing, antihistaminic, and anti-inflammatory properties. Corticosteroids are considered to be more potent than other antiallergic drugs, and modifications in their molecular structures have made certain corticosteroids suitable for the treatment of ocular allergy.
Curr Allergy Asthma Rep 2001 Jul
PMID:Overview of ocular allergy treatment. 1189 61

The clinical presentation of the various forms of allergic conjunctivitis varies greatly from mild symptoms to severe disease with vision-threatening complications. Although an IgE-mediated type-1 hypersensitivity reaction has been demonstrated or postulated in many types of allergic eye disease, the pathophysiology underlying the allergic conjunctivitides is not fully understood. The variety of currently available treatment options underscores the complexity of the chemical reactions associated with mast cell degranulation and mediator release causing the onset of allergic signs and symptoms. Many of these treatments are merely palliative and do not eliminate the complex immune response initiating the symptoms, so there is a recurrence of disease as soon as the therapy is discontinued. Models of allergic eye disease have significantly aided the discovery of new anti-allergic and anti-inflammatory compounds that can be used safely in the eye.
Curr Allergy Asthma Rep 2001 Nov
PMID:The pathogenesis of allergic conjunctivitis. 1189 84

Allergic conditions contribute significantly to the burden of chronic disease in the industrialized world. Current treatments offer varying degrees of palliation. The sole proven disease-modifying strategy, specific or whole-allergen immunotherapy, is limited because of the associated risk of systemic adverse effects, such as anaphylaxis. Short, linear allergen-derived peptides, corresponding to T cell epitopes, offer the possibility of a safer approach as they are capable of inducing allergen-specific hyporesponsiveness without cross-linking mast cell-bound IgE. This review evaluates the scientific basis of peptide immunotherapy and clinical experience in allergy up to the present time.
Curr Allergy Asthma Rep 2002 Mar
PMID:The potential of peptide immunotherapy in allergy and asthma. 1189 95

Mast cells are involved in early and late-phase reactions by releasing vasoactive molecules, proteases, and cytokines. Azelastine and olopatadine are histamine 1 receptor (H-1R) antagonists with antiallergic effects present in the ophthalmic solutions Optivar and Patanol, respectively. Because it is difficult to obtain animal or human conjunctival tissue, we first investigated the effect of these compounds on histamine and tryptase release from cultured human mast cells (CHMCs) grown out of human umbilical cord blood-derived CD34+ cells. Sensitized CHMCs were pretreated with various concentrations of azelastine or olopatadine for 5 minutes. Then, CHMCs were challenged with anti-immunoglobulin E (IgE) and the released mediators were quantitated. The greatest inhibition of mediator release was seen when CHMCs were pretreated with 24 microM of azelastine or 133 microM of olopatadine (2% dilution of azelastine or 5% olopatadine original ophthalmic solutions, respectively). We then studied the drug concentrations that gave optimal results on skin vasodilation induced by the mast cell secretagogue compound 48/80. An intradermal injection of 48/80 in rats, to which Evan's blue had been administered via the tail vein, induced substantial dye extravasation. Pretreatment of the injection site for 5 minutes with either 24 microM of azelastine or 133 microM of olopatadine completely prevented extravasation; this effect was quantitated also by fluorometric assessment of Evan's blue extracted in formamide. Evaluation of skin mast cells from injected sites showed that mast cell degranulation was inhibited greatly. These results indicate that on an equimolar basis, azelastine was a more potent inhibitor than olopatadine of both CHMC and rat skin mast cells activation.
Allergy Asthma Proc
PMID:Azelastine's inhibition of histamine and tryptase release from human umbilical cord blood-derived cultured mast cells as well as rat skin mast cell-induced vascular permeability: comparison with olopatadine. 1189 34

Anaphylaxis represents the maximal variant of an immediate-type allergic reaction involving the whole organism with manifestations in different organ systems. IgE-mediated mast cell and basophil activation is the major pathomechanism; however, immune complex and pseudo-allergic reactions also may lead to the same symptomatology. The most common elicitors are drugs, additives, occupational substances, animal venoms, aeroallergens, and contact urticariogens but also physical factors (cold, heat, ultraviolet light, exercise). When no eliciting factors can be detected, the term "idiopathic anaphylaxis" is used. The diagnosis of idiopathic anaphylaxis is, therefore, a diagnosis of exclusion and may be made only after careful allergy history taking and diagnosis involving in vitro tests. Possible mechanisms underlying the pathophysiology of idiopathic anaphylaxis include undetected diseases (eg, mastocytosis occulta), concomitant anaphylaxis-enhancing medication (b-blockers), secretion of histamine-releasing factor from T lymphocytes, autoantibodies against IgE or IgE receptors, and angiotensin II deficiency. One of the many differential diagnoses of anaphylaxis may have been overlooked. The treatment of idiopathic anaphylaxis follows the rules of antianaphylactic therapy.
Curr Allergy Asthma Rep 2002 Jan
PMID:Idiopathic anaphylaxis. 1189 24

Asthma therapy, like other therapies, has been moving towards a molecular basis for several years. This year, there have been several preclinical studies published which utilize attributes or facets of DNA to address asthma therapeutics. These include antisense oligonucleotides (against the nuclear transcription factor GATA-3 and the mast cell chemotactic agent, stem cell factor), gene transfer (of interleukin-18, both by plasmid and viral vectors), and CpG oligodeoxynucleotides (which suppress Th2 and stimulate Th1 responses). No clinical experience has yet been reported for any of these areas of research in asthma, but clinical trials are ongoing utilizing CpG oligonucleotides.
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PMID:DNA therapy for asthma. 1196 53

Paclitaxel (Taxol) a taxane antineoplastic agent causing irreversible microtubule aggregation with activity against breast, ovarian, lung, head and neck, bladder, testicular, esophageal, endometrial and other less common tumors was derived from the bark of the Pacific yew (Taxus brevifolia). Phase I trials conducted in the late 1980s were almost halted because of the high frequency of hypersensitivity-like reactions. Respiratory distress (dyspnea and/or bronchospasm), hypotension, and angioedema were the major manifestations, but flushing, urticaria, chest, abdomen, and extremity pains were described also. Reactions occurred on first exposure in the majority of cases raising etiologic questions. The vehicle for paclitaxel Cremophor EL (polyoxyethylated castor oil in 50% ethanol) was strongly suspect as a direct (non-immunoglobulin E dependent) histamine releaser. Premedication regimens and longer infusion times lowered the incidence of reactivity allowing phase II and III trials to progress through the early 1990s. The mechanism(s) underlying paclitaxel hypersensitivity-like reactions is still unknown, and clinical data on probable complement and mast cell activation are lacking. The original clinical trial protocols for paclitaxel required discontinuation of therapy for patients who experienced hypersensitivity-like reactions. Here, we review the current etiologic knowledge of these reactions and describe our clinical approach to allow completion of chemotherapy with this powerful plant-derived agent.
Allergy Asthma Proc
PMID:Taxol reactions. 1212 9

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.
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PMID:New insights into the relationship between airway inflammation and asthma. 1214 12

Asthma is a complex condition in which exposure to environmental antigens induces inflammatory reactions in the airway characterized by activation of mast cells and eosinophils. Mast cells are known to be the main effector cells in eliciting IgE-mediated allergic response. These cells secrete various substances that perpetuate inflammation and provoke airway smooth muscle (ASM) contraction. A newly recognized addition to the repertoire of FcepsilonRI-mediated signaling events is the activation of sphingosine kinase leading to the generation of the potent sphingolipid mediator, sphingosine-1-phosphate (S1P) from sphingosine. S1P secretion by the lung significantly increases after challenge with an allergen, adding this sphingolipid metabolite to the variety of mediators that are released during an allergic reaction [FASEB J. 15 (2001) 1212]. Indeed, similar to previous reports, we found that FcepsilonRI cross-linking not only increased cellular levels of S1P, it also markedly enhanced its secretion from rat basophilic leukemia RBL-2H3 cells. Moreover, S1P induced degranulation of RBL and bone marrow derived mast cells (BMMCs) cells as determined by hexosaminidase release. Treatment of BMMCs with the sphingosine kinase inhibitors, DL-threo-dihydrosphingosine and dimethylsphingosine, reduced IgE/Ag stimulated histamine release. RT-PCR analysis demonstrated that these mast cells express S1P receptors EDG-1 and EDG-5 but not EDG-3, EDG-6 or EDG-8 transcripts. Further studies are needed to determine whether IgE triggering results in transactivation of EDG-1 or EDG-5 present on mast cells and whether this is a critical event for mast cell activation.
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PMID:The roles of sphingosine-1-phosphate in asthma. 1221 90

Interleukin (IL) 6 is a pleiotropic cytokine (26 kDa) that originally was named interferon beta 2 or B cell-stimulating factor or differentiating B cell factor inducing immunoglobulin production. IL-6 is produced in many diseases. After secretion, IL-6 binds to its receptor IL-6R alpha (gp 80), the IL-6R alpha complex then recruits the signal-transducing beta-subunit (gp 130), which is the functional complex for signal transduction. In addition, activation of Th2 cells or mast cells also produce IL-6, which mediates immune responses, inflammation, acute phase responses, hematopoiesis, cancer, inflammatory bowel disease, etc. IL-6 also is a crucial cytokine for mast cell maturation. Human cord blood CD34+ cells differentiate and grow into mast cells in the presence of stem cell factor (SCF) and IL-6, causing increases in cell size, frequency of chymase positive cells, and intracellular histamine levels when compared with cells treated with SCF alone. Activated mast cells increase IL-6 mRNA associated with protein kinase C (PKC) activity. IL-6 also up-regulates histamine production rather than increases its storage and is an important inducing factor for the expression of immunoglobulin E (IgE) Fc epsilon RI.
Allergy Asthma Proc
PMID:Interleukin-6 and mast cells. 1247 43


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