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)

135 patients were entered into a 28-day randomized double-masked multicentre study comparing the efficacy and short-term safety of lodoxamide 0.1% ophthalmic solution (Alomide--Alcon Laboratories), a mast cell stabilizer, with sodium cromoglycate 2% ophthalmic solution (Opticrom--Fisons Pharmaceuticals) in the treatment of allergic eye disease. Patients given lodoxamide 0.1% showed a significantly more rapid and greater improvement in their signs and symptoms of allergic eye disease than patients given sodium cromoglycate 2%. Both treatments were found to be safe, and side-effect profiles were comparable between the two treatment groups, although the overall incidence of side-effects in this study was found to be less frequent in the lodoxamide-treated group.
 ...
PMID:Randomised double-masked trial of lodoxamide and sodium cromoglycate in allergic eye disease. A multicentre study. 145 Jun 59

Sodium cromoglycate stabilizes mast cell membranes and prevents the release of histamine and other biochemical mediators. When topically applied to the eye before allergen exposure, ocular sodium cromoglycate prevents many of the signs and symptoms associated with type I allergic reactions (which includes hayfever, acute allergic and chronic allergic conjunctivitis, and vernal keratoconjunctivitis) and giant papillary conjunctivitis. Although difficulties exist in evaluating clinical trials in allergic eye disease, both open and controlled studies have shown ocular sodium cromoglycate to be very effective in relieving the subjective symptoms and clinical signs of the above ocular disorders. In addition, ocular sodium cromoglycate may decrease the need for supplementary oral antihistamines and, more importantly, the need for ocular corticosteroids, thus decreasing the incidence of steroid-induced ocular side effects. However, in severe cases and in instances of acute exacerbation of symptoms, the combined ocular application of sodium cromoglycate and corticosteroids may be very effective. No systemic or severe adverse reactions have been attributed to ocular sodium cromoglycate, which is not surprising since systemic drug absorption from the eye is minimal. However, transient local stinging and burning have been reported. Thus, although further studies in giant papillary conjunctivitis and comparative studies with corticosteroids in allergic conjunctivitis and vernal keratoconjunctivitis are needed to more clearly define the extent of benefits that may be obtained from ocular sodium cromoglycate, it is clear that the safety and efficacy of the drug in type I allergic eye diseases is such that it should be considered as a first-line agent when drug therapy of these disorders is indicated.
 ...
PMID:Ocular sodium cromoglycate. An overview of its therapeutic efficacy in allergic eye disease. 308 17

Immuno-histopathological studies of conjunctival tissue biopsied from patients with non-sight-threatening allergic conjunctivitis or with sight-threatening allergic keratoconjunctivitis should lead to more effective management of these eye conditions, based on the specific cellular involvement. The major difference between these two categories of eye disease was the occurrence of T-lymphocytes, which were absent in the former but prominent in the sight-threatening disorders. Seasonal and perennial allergic conjunctivitis both showed a heavy mast cell increase, due to infiltration of mucosal type mast cells, and allergen challenge studies linked mast cell histamine release to the early phase reaction occurring within 20 minutes. A second histamine peak at six hours after challenge might implicate basophils (or refractory mast cells) and was accompanied by a rise in eosinophil cationic protein. In sight-threatening, chronic allergic keratoconjunctivitis the responses were clearly directed by T-cells, themselves the primary effector cell in atopic keratoconjunctivitis, whereas vernal keratoconjunctivitis displayed a T-cell driven eosinophilia, with increased expression of the adhesion molecules involved in tissue invasion by these cells. Appropriate therapies for each different category of conjunctivitis should be based on the specific immunopathology, and directed at the activated cell types that are primarily responsible for the disease process.
 ...
PMID:Therapeutic considerations: symptoms, cells and mediators. 754 Mar 64

Allergic eye disease has a variety of clinical manifestations including seasonal atopic conjunctivitis (SAC), perennial atopic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), and atopic blepharoconjunctivitis (ABC). We have investigated the number, distribution and protease expression of mast cells in normal and diseased conjunctiva with the use of immunohistochemistry in water-miscible resin sections. The median mast cell densities in normal subjects were 17 mm-2 in the bulbar substantia propria and 9 mm-2 in tarsal substantia propria. Mast cells were absent from the normal conjunctival epithelium at both sites. Mast cell densities were increased in the bulbar substantia propria in SAC, AKC and ABC. Tarsal substantia propria showed a significant increase in mast cells in ABC and AKC disease states. Mast cells express a range of proteases which varies according to their anatomic site. Mast cells in connective tissue are described to contain tryptase, chymase, cathepsin-G and carboxypeptidase-A, whereas mucosal mast cells contain only tryptase. In the diseased conjunctiva there was a marked reduction in proteases other than tryptase in the intraepithelial mast cells. There were also significant reductions in protease expression other than tryptase in the bulbar substantia propria in AKC and ABC. There appear to be specific alterations in the distribution of mast cells in the sub-categories of allergic eye disease. The distinction between mucosal and connective tissue mast cell phenotypes is not clear-cut and may depend on the functional state of the mast cells in relation to the microenvironment.
 ...
PMID:Mast cell distribution and neutral protease expression in acute and chronic allergic conjunctivitis. 772 24

New sources of human and mouse mast cells, which were isolated from individual organs (i.e., lung, colon, synovium, skin, uterus, heart), developed from progenitors in vitro in the presence of stem cell factor and/or interleukin (IL)-3, or enriched from fetal or adult blood, spleen or bone marrow by cell sorting, have made possible new studies of the cell biology of mast cells. Advances resulting from these new mast cell sources as well as from new methods for labeling specific products in subcellular sites and structures in resting and functional mast cells are the subject of this review. Specific advances discussed are as follows: identification of an Fc epsilonRI+ c-kit- mouse basophil population from bone marrow and spleen that is associated with IL-4 production and an Fc epsilonRI- c-kit- granulated mouse mast cell progenitor in fetal blood; identification of hyperplasia and functional activation of human skin mast cells in vivo when exposed to recombinant stem cell factor and spontaneous degranulation in X-linked immunodeficient mouse mast cells; use of an enzyme-affinity-gold method to detect histamine in mature and immature human mast cell granules, in secretion and recovery of histamine during anaphylactic degranulation of human lung mast cells ex vivo, and in secretion of histamine in vivo by piecemeal degranulation of IL-4 transgenic mouse mast cells in inflammatory eye disease and of human gut mast cells in inflammatory bowel disease; use of immunogold methods to localize cyclooxygenase and tumor necrosis factor-alpha to subcellular structures in human and rat mast cells and to localize the Charcot-Leyden crystal protein in human basophils to aid in the identification of mast cells arising in mixed cellular populations; use of a low-density lipoprotein (LDL)-gold affinity method to demonstrate a rat mast cell granule-mediated uptake of LDL by macrophages in peritoneal fluid.
 ...
PMID:New aspects of mast cell biology. 930 24

Atopic keratoconjunctivitis (AKC) is a chronic allergic eye disease. Although the pathogenesis is not fully understood, some impairment in cell-mediated immunity was suggested by histopathological findings in conjunctival specimens obtained from affected individuals. T-cell infiltration and an enhanced T-helper/T-suppressor cell ratio in conjunctival biopsy specimens were observed previously by immunofluorescence procedures. We analyzed the cells in tears of patients with AKC using flow cytometry (FCM) and compared the results to those of normal subjects to identify the role of T lymphocytes in the pathogenesis of the disease. The tear samples of the patients and normal subjects were collected with capillary tubes, and the surface receptors of cells were detected with FCM. Statistical analyses were performed with Student's t test. The percentages of T cells, activated B cells, and T-helper/T-suppressor cell ratios were found to be higher in the tears of patients with AKC than in controls. We propose that a decreased T-suppressor cell concentration in tears may enhance immunoglobulin-E production of B cells, and the signs and symptoms are provoked by inflammatory mediators liberated from mast cell degranulation.
 ...
PMID:Analysis of tears in patients with atopic keratoconjunctivitis, using flow cytometry. 948 87

Biochemical determinations of the histamine content and secretion from basophils and mast cells have been available for some time, and much of the complex anatomy of these cellular populations and their release reactions has been documented using the electron microscope. The ultrastructural analyses led to the description of vesicular transport between secretory granules and the plasma membrane as a mechanism for secretion from basophils and mast cells--a process termed piecemeal degranulation. Proof of concepts incorporated in a general degranulation model put forth in 1975 (DVORAK, H.F. and DVORAK, A.M.) requires high magnification imaging of a granule constituent in trafficking vesicles in the process of a stimulated release reaction in which the constituent release is monitored biochemically. Development and application of a new enzyme-affinity method to detect histamine at high magnifications in well-preserved ultrastructural samples have provided the necessary means to establish proof that appropriate secretagogues can stimulate the vesicular transport of histamine in basophils and mast cells during release reactions monitored biochemically. The background information necessary to the understanding of this result is presented here, as well as the development and verification of the diamine oxidase-gold method to image histamine in human mast cell granules as the test system. Also presented are applications using this technology to examine histamine stores and secretion in vitro, in vivo, and ex vivo in human basophils and mast cells and in mouse mast cells. Specifically examined are histamine stores developing in maturing mast cells induced to develop de novo from cultured human cord blood cells, secretagogue-stimulated release and recovery of histamine stores from isolated, purified human lung mast cells ex vivo, cytokine-stimulated degranulation of human skin mast cells and their histamine stores in vivo, piecemeal degranulation of human gut mast cells and their histamine stores in inflammatory bowel disease in vivo, piecemeal degranulation of mouse skin mast cells and their histamine stores in inflammatory eye disease in an interleukin-4 transgenic mouse model in vivo, and the stimulated secretion and recovery of histamine from human basophils ex vivo.
 ...
PMID:Histamine content and secretion in basophils and mast cells. 1031 76

Allergic eye disease is a common clinical problem adversely affecting the quality of life for millions of sufferers. This ocular process is associated with IgE-mediated conjunctival inflammation leading to signs of immediate hypersensitivity including redness, itching, and tearing. Pathologic studies have shown that the conjunctiva contains mast cells that when sensitized with IgE antibody and exposed to environmental allergens can release mediators of allergic inflammation. The type, release kinetics, and concentration of these mediators in the conjunctiva have not been completely characterized. The ability to isolate and purify mast cells and epithelial cells from human conjunctival tissue has permitted the study of mediator release and cell-to-cell signaling in this tissue. Our laboratory has developed in vitro and in vivo models to better understand how inflammatory cells are recruited to and infiltrate conjunctival tissues. These models demonstrate that mast cell activation may supply sufficient cytokine signaling to initiate and direct the well-orchestrated trafficking of eosinophils to the ocular surface, facilitate their adhesion, and cause release of potent mediators of ocular inflammation.
 ...
PMID:Conjunctival mast cells in ocular allergic disease. 1142 71

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.
 ...
PMID:The pathogenesis of allergic conjunctivitis. 1189 84

Ocular allergies are very common and range in intensity from mild, self-resolving, acute conditions to serious, chronic disease that can severely affect vision. The vast majority of sufferers experience relatively mild symptoms, which are often seasonal in nature. Treatments should be simple, comfortable and very safe. They should be able to respond to an ongoing attack but also provide long-term relief from symptoms. Mast cell degranulation is central to all forms of ocular allergic disease and so treatment has concentrated on preventing this process or antagonizing the effects of the primary mediator, histamine. Olopatadine is a relatively new selective H1 antagonist that has mast cell stabilizing properties and has been shown to affect release of TNFalpha and various cytokines from conjunctival epithelial cells. This paper reviews the local ocular use of olopatadine and discusses the place of the drug in the treatment of allergic eye disease.
 ...
PMID:A review of the use of olopatadine in allergic conjunctivitis. 1584 17


1 2 Next >>