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)

Previous studies indicate that there is an increase in the number of detectable mast cells expressing gonadotropin-releasing hormone-like immunoreactivity (GnRH-ir) in the medial habenular region of the brain in ring doves after a period of 2 hr of courtship. In the present experiment the overall distribution of GnRH-ir mast cells in the brain is described, and the influence of behavioral and endocrine state on brain mast cell distribution and detectable mast cell number is explored. Four groups of male birds were studied: (1) paired with a female and displaying courtship behavior, (2) paired with a squab and displaying aggressive behavior, (3) visually isolated from other doves, and (4) long-term castrates housed communally. In all four groups, GnRH-ir mast cells were observed in the following areas: the medial habenula, circumventricular organs, organum vasculosum lamina terminalis and organum subseptale, the pia mater, and blood vessels. Cell counting revealed differences among groups in numbers of habenular mast cells. Courted doves had the most habenular mast cells, followed by doves paired with squabs, and then visually isolated doves, while castrates had the fewest. One-way ANOVA indicates significant differences among groups. All pairwise comparisons show that the courting animals had significantly more detectable mast cells in the habenular area than did visually isolated and castrated groups. These results suggest that the appearance and/or detectability of GnRH-ir mast cells in the habenula is related to the behavioral state and possibly to the endocrine state of the animal and suggest a novel mechanism for interactions among the nervous, endocrine, and immune systems.
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PMID:Reproductive behavior, endocrine state, and the distribution of GnRH-like immunoreactive mast cells in dove brain. 822 53

The principal function of the mucosal immune system is to protect the mucosa from exogenous aggression. It also involves a lymphocyte recirculation phenomenon allowing activated lymphocytes to migrate to the aggressed site, for example the bronchi, and to recirculate and colonize other sites of the mucosal immune system. In asthma, analysis of the other sites of the common mucosal immune system demonstrates asthma-like inflammatory reactions in the accessory salivary glands and the gut: lymphocyte infiltrate, mast cell activation, thickening of the basal membrane, accumulation and activation of eosinophils (gut), activation of endothelial cells expressing ICAM-1. Lymphocyte, eosinophil and mast cell infiltration is observed in the digestive tract as well as increased expression of IL-3, IL-5 and GM-CSF. The similarity of the anomalies observed in BALT and GALT tissues would suggest the entire mucosal immune system is implicated in asthma.
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PMID:[The common mucosal immune system in respiratory disease]. 1113 72

Aggressive mastocytosis is a form of systemic mast cell disease (SMCD) characterized by organ infiltration, bone lesions. eosinophilia and lymphadenopathies. Here we report a patient with unusual clinical features, namely osteolysis without other bone lesions commonly found in SMCD, major eosinophilia and cerebral infarction. The mast cells exhibited a classical immunophenotype (CD2+, CD9+, CD13+, CD25+, CD35+, CD45c+ and CD117+). Cytogenetic investigation showed novel complex aberrations, and clonal evolution was correlated with clinical progression. The screening for recurrent point mutations affecting the c-kit gene was negative. Mainly, the ASP816VAL substitution was not detected in our patient. Treatment with steroids and interferon was only temporarily effective.
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PMID:Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage. 1144 35

Systemic mastocytosis (SM), as opposed to cutaneous-only mastocytosis, implies the presence of neoplastic mast cell infiltration in extracutaneous tissue. Mast cell disease in adults is often systemic and often involves the bone marrow. Typical clinical and laboratory features of SM include urticaria pigmentosa, mast cell mediator symptoms (eg, headache, flushing, lightheadedness, urticaria and pruritus, nausea, diarrhea, abdominal pain, and vasodilatory shock), bone pain (eg, osteoporosis, lytic bone lesions, and fractures), hepatosplenomegaly, cytopenia, eosinophilia, elevated serum tryptase and histamine, and bone marrow fibrosis and angiogenesis. SM may be indolent (no evidence of organ dysfunction), aggressive (presence of organ dysfunction), associated with another often chronic myeloid hematologic disease (SM-AHD), or present as mast cell leukemia or sarcoma. Mast cell-mediator symptoms are treated with histamine antagonists and cromolyn sodium. Indolent SM does not require cytoreductive therapy. Aggressive SM and SM-AHD are managed based on their molecular profile. Recent information suggests that FIP1-like-1-platelet-derived growth factor receptor-alpha(+) SM responds well to imatinib mesylate, whereas interferon-alpha should be considered as a first-line treatment in all of the other cases, including patients with Asp816Val(+) SM. Cladribine has been shown to be effective in patients who develop resistance to interferon treatment.
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PMID:Systemic mastocytosis: current concepts and treatment advances. 1508 68

Aggressive mast cell (MC) tumors are hematopoietic neoplasms characterized by uncontrolled growth of MC and resistance to conventional drugs. In most cases, the tyrosine kinase (TK) receptor KIT is involved in malignant cell growth. Therefore, several KIT TK-targeting drugs are currently being tested for their ability to block growth of neoplastic MC. We examined the effects of four TK inhibitors (imatinib, midostaurin, nilotinib, and dasatinib) on C2 canine mastocytoma cells, as well as primary neoplastic canine MC. As assessed by (3)H-thymidine incorporation experiments, all TK inhibitors produced dose-dependent inhibition of proliferation in C2 cells with the following IC(50) values: imatinib: 269 +/- 180 nM, midostaurin: 157 +/- 35 nM, nilotinib: 55 +/- 24 nM, dasatinib: 12 +/- 3 nM. Growth-inhibitory effects of TK inhibitors were also observed in primary neoplastic mast cells, although IC(50) values for each drug varied from patient to patient, with midostaurin being the most potent agent in all samples tested. In consecutive experiments, we were able to show that TK inhibitors cooperate with each other in producing growth inhibition in C2 cells with synergistic effects observed with most drug combinations. In flow cytometry and TUNEL assay experiments, growth-inhibitory effects of TK inhibitors were found to be associated with cell-cycle arrest and apoptosis. Together, these data show that several TK-targeting drugs induce apoptosis and inhibit proliferation in canine mastocytoma cells in vitro, and that synergistic drug interactions can be obtained. Clinical trials are now warranted to explore whether these TK inhibitors also counteract growth of neoplastic cells in vivo in patients with aggressive MC tumors.
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PMID:Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells. 1768 69

Mastocytosis is a heterogeneous entity that may present as either a cutaneous or systemic disease. Progression of pediatric cutaneous mastocytosis (CM) is uncommon, but in adults, this condition persists and often progresses to systemic disease. Mast cell proliferation and differentiation from stem cell precursors depend on a number of factors, including a mast cell tyrosine kinase receptor (kit) and its ligand (the stromal cell-derived cytokine stem cell factor). A gain-of-function mutation in codon 816 of c-kit is frequently present in mast cells of patients with systemic mastocytosis (SM). The diagnostic approach for a patient with suspected mast cell disease includes a thorough skin examination, a skin biopsy, a serum tryptase level, and bone marrow aspiration and biopsy. The treatment is directed toward avoidance of triggers of mast cell mediator release and management of symptoms. Aggressive cases are managed with cytoreductive therapies, such as interferon alfa-2b and cladribine. Research has been directed at more specific treatment modalities, including specific kit tyrosine kinase inhibitors.
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PMID:Systemic mastocytosis: classification, pathogenesis, diagnosis, and treatment. 1927 68

Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3-1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin.
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PMID:Bifidobacterium longum lysate, a new ingredient for reactive skin. 1962 30

Mastocytosis (MC) encompasses a range of disorders characterized by a clonal, pathological accumulation of mast cells having a somatic activating mutation of the tyrosine kinase receptor Kit (exon 17, codon 816; D816V) in more than 90 % of adult patients. The mutation is much less common in children. Skin and bone marrow are most often affected. Symptoms and clinical course are very heterogeneous due to a variable degree of local or systemic mediator release or organ dysfunction as a result of mast cell infiltrates. Pruritus, wheals, flushing and gastrointestinal symptoms are often reported. The majority of pediatric patients experience spontaneous remission of MC. Adults usually have chronic disease, rarely transforming into an aggressive or lethal type. Indolent systemic MC with involvement of skin and bone is the most common type. In MC the risk for anaphylactic reactions following an insect sting (and other causes of mast cell activation) is increased significantly. Diagnostic hallmarks are biopsies from skin and bone marrow using tryptase antibodies for staining as well as serum tryptase levels. At present a curative treatment for MC is not available. Systemic histamine H(1) receptor antagonists are widely used. Aggressive types of MC respond partially to IFN-alpha or cladribine. A variety of receptor tyrosine kinase inhibitors is still under critical evaluation for systemic treatment of MC. After introduction of the WHO classification for MC and the development a German MC guideline, as well as the foundation of national and international competence networks for MC, a significantly improved quality of medical care for MC patients can be expected for the future.
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PMID:Mastocytosis - an update. 2067 51

A 12-year-old male presented with an 8-year history of five firm cream colored papules on the right vertex of the scalp. A biopsy showed a dense infiltrate of monomorphous mast cells involving the dermis and extending into the subcutis. A relatively well-circumscribed cluster of larger cells showed pleomorphic nuclei with bilobed and multilobed morphology. Both mast cell populations had an eosinophilic cytoplasm filled with granules ranging in size from small to giant forms. By immunohistochemistry, the cells expressed CD117, tryptase and CD68, and were negative for AE1/AE3, CD1a, CD2 and CD25. S-100 staining revealed only faint cytoplasmic positivity and myeloperoxidase had an inhomogeneous patchy pattern, with an overall staining of less than 5% of the cells. A diagnosis of cutaneous mastocytosis was made and after 6 months follow-up, no progression observed. Clinical correlation and awareness of these unusual morphologic features as being part of the spectrum of cutaneous mastocytosis are important to avoid an erroneous diagnosis of malignancy. Although pleomorphic, multilobed nuclear morphology and giant cytoplasmic granules have not been associated with an aggressive behavior or systemic mastocytosis, close clinical observation is warranted in this context.
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PMID:Cutaneous mastocytosis with atypical mast cells and giant cytoplasmic granules. 2272 60

Mast cell tumors are uncommon in horses and typically have a benign clinical course, but there are occasional reports of more aggressive behavior. The objective of this study was to review histologic features and KIT expression patterns of 72 previously diagnosed equine cutaneous mast cell tumors to determine if either is associated with clinical outcomes. Biopsy specimens were reviewed using histologic criteria derived from grading schemes, and KIT antibody expression patterns used in canine tumors and surveys were sent to referring veterinarians for follow-up clinical data. Arabians were overrepresented relative to the reference population. Most tumors were well differentiated with low mitotic rates (96%), and aberrant KIT staining patterns, as described in dogs, were uncommonly identified (12%). Associated clinical disease was uncommon and no tumors exhibited malignant behavior. Overall, KIT staining pattern and histologic features were not associated with poor clinical outcome or abnormal tumor behavior.
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PMID:Histologic characteristics and KIT staining patterns of equine cutaneous mast cell tumors. 2379 48


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