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)

A man developed acne keloidalis-like lesions in the scalp during treatment with diphenylhydantoin and carbamazepine for epilepsy. These drugs were suspected to play a role in the pathogenesis of this skin disease in an unusual location, based on clinical evidence and on the in vitro test, mast cell degranulation (MCD).
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PMID:Acne keloidalis-like lesions on the scalp associated with antiepileptic drugs. 224 43

Excessive glutamatergic neurotransmission, particularly when mediated by the N:-methyl-D-aspartate (NMDA) subtype of glutamate receptor, is thought to underlie neuronal death in a number of neurological disorders. Histamine has been reported to potentiate NMDA receptor-mediated events under a variety of conditions. In the present study we have utilized primary hippocampal neurone cultures to investigate the effect of mast cell-derived, as well as exogenously applied, histamine on neurotoxicity evoked by excessive synaptic activity. Exposure of mature cultures for 15 min to an Mg(2+)-free/glycine-containing buffer to trigger synaptic transmission through NMDA receptors, caused a 30-35% neuronal loss over 24 h. When co-cultured with hippocampal neurones, activated mast cells increased excitotoxic injury to 60%, an effect that was abolished in the presence of histaminase. Similarly, addition of histamine during magnesium deprivation produced a concentration-dependent potentiation (+ 60%; EC(50) : 5 microM) of neuronal death which was inhibited by sodium channel blockers and NMDA receptor antagonists, although this effect did not involve known histamine receptors. The histamine effect was further potentiated by acidification of the culture medium. Cultures 'preconditioned' by sublethal (5 min) Mg(2+) deprivation exhibited less neuronal death than controls when exposed to a more severe insult. NMDA receptor activation and the extracellular regulated kinase cascade were required for preconditioning neuroprotection. The finding that histamine potentiates NMDA receptor-mediated excitotoxicity may have important implications for our understanding of conditions where enhanced glutamatergic neurotransmission is observed in conjunction with tissue acidification, such as cerebral ischaemia and epilepsy.
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PMID:Potentiation by histamine of synaptically mediated excitotoxicity in cultured hippocampal neurones: a possible role for mast cells. 1114 77

EL mice have been used as a model of epilepsy, whereas ASK mice are an epilepsy-resistant variant originating from a colony of EL mice. Mast cell-dependent anaphylaxis is easily inducible by stimulation with IgE and Ag in ASK mice, whereas EL mice are resistant to such stimuli. In this study we have characterized mast cells derived from these two strains. ASK mast cells proliferated more vigorously than EL cells in response to IL-3 and stem cell factor. Although ASK mast cells degranulated less vigorously than EL mast cells upon stimulation with IgE and Ag, ASK cells produced and secreted several-fold more TNF-alpha and IL-2 than EL cells. Consistent with the similarities of these ASK and EL mast cell responses with phenotypes of lyn(-/-) and wild-type mast cells, respectively, Lyn activity was reduced in ASK cells. In addition to the impaired Lyn activity, ASK cells just like lyn(-/-) cells exhibited reduced Syk activity, prolonged activation of ERK and JNK, and enhanced activation of Akt. Furthermore, the lipid raft-resident transmembrane adaptor protein Cbp/PAG that associates with Lyn was hypophosphorylated in ASK cells. Importantly, similar to lyn(-/-) cells, Fyn was hyperactivated in ASK cells. Therefore, these results are consistent with the notion that Lyn-dependent phosphorylation of Cbp/PAG negatively regulates Src family kinases. This study also suggests that reduced activity of Lyn, a negative regulator of mast cell activation, underlies the susceptibility of ASK mice to anaphylaxis and implies that dysregulation of Lyn and other Src family kinases contributes to epileptogenesis.
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PMID:Dysregulation of Src family kinases in mast cells from epilepsy-resistant ASK versus epilepsy-prone EL mice. 1718 84

A sixty-four year old man with a past history of hypercholesterolemia, asthma, food allergy, epilepsy and myocardial infarction was admitted to the emergency department because of a generalized erythema, nausea, vomiting, and chest pain after taking an oral dose of amoxicillin. Electrocardiography showed ST segment elevation in anterior leads. After coronary angiography, type 2 variant of Kounis syndrome was diagnosed. We present the first case of oral amoxicillin induced Kounis syndrome in an asthmatic patient with severe anaphylactic shock. The present report also shows that atopic people expressing an amplified mast cell degranulation may have more serious hemodynamic decompensation during hypersensitivity reactions. Case selective mast cell surface membrane stabilization should be considered a potential therapeutic strategy for people with food induced allergy, for atopic patients and for patients who have already experienced a first Kounis syndrome.
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PMID:Kounis syndrome secondary to amoxicillin use in an asthmatic patient. 2022 32

One of the more important recent advances in neuroscience research is the understanding that there is extensive communication between the immune system and the central nervous system (CNS). Proinflammatory cytokines play a key role in this communication. The emerging realization is that glia and microglia, in particular, (which are the brain's resident macrophages), constitute an important source of inflammatory mediators and may have fundamental roles in CNS disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Microglia respond also to proinflammatory signals released from other non-neuronal cells, principally those of immune origin. Mast cells are of particular relevance in this context. These immunity-related cells, while resident in the CNS, are capable of migrating across the blood-spinal cord and blood-brain barriers in situations where the barrier is compromised as a result of CNS pathology. Emerging evidence suggests the possibility of mast cell-glia communications and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization, both peripherally and centrally. This review aims to provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of microglia, neuroimmune interactions involving mast cells, in particular, and the possibility that mast cell-microglia crosstalk may contribute to the exacerbation of acute symptoms of chronic neurodegenerative disease and accelerate disease progression, as well as promote pain transmission pathways. We conclude by considering the therapeutic potential of treating systemic inflammation or blockade of signaling pathways from the periphery to the brain in such settings.
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PMID:Microglia and mast cells: two tracks on the road to neuroinflammation. 2251 95

Communication between the immune and nervous systems depends a great deal on pro-inflammatory cytokines. Both astroglia and microglia, in particular, constitute an important source of inflammatory mediators and may have fundamental roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Glial cells respond also to pro-inflammatory signals released from cells of immune origin. In this context, mast cells are of particular relevance. These immune-related cells, while resident in the CNS, are able to cross a compromised blood-spinal cord and blood-brain barrier in cases of CNS pathology. Emerging evidence suggests the possibility of mast cell-glia communication, and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. This review aims to provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of glia, neuro-immune interactions involving mast cells and the possibility that glia-mast cell interactions contribute to exacerbation of acute symptoms of chronic neurodegenerative disease and accelerated disease progression, as well as promotion of pain transmission pathways. Using this background as a starting point for discussion, we will consider the therapeutic potential of naturally occurring fatty acid ethanolamides, such as palmitoylethanolamide in treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.
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PMID:Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide. 2310 49

Glia and microglia in particular elaborate pro-inflammatory molecules that play key roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Microglia respond also to pro-inflammatory signals released from other non-neuronal cells, mainly those of immune origin such as mast cells. The latter are found in most tissues, are CNS resident, and traverse the blood-spinal cord and blood-brain barriers when barrier compromise results from CNS pathology. Growing evidence of mast cell-glia communication opens new perspectives for the development of therapies targeting neuroinflammation by differentially modulating activation of non-neuronal cells that normally control neuronal sensitization - both peripherally and centrally. Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can be up-regulated as a result of tissue damage or stimulation of inflammatory responses. Such molecules include the N-acylethanolamine family. One such member, N-palmitoylethanolamine is proposed to have a key role in maintenance of cellular homeostasis in the face of external stressors provoking, for example, inflammation. N-Palmitoylethanolamine has proven efficacious in mast-cell-mediated experimental models of acute and neurogenic inflammation. This review will provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of microglia, neuroimmune interactions involving mast cells and the possibility that mast cell-microglia cross-talk contributes to the exacerbation of acute symptoms of chronic neurodegenerative disease and accelerates disease progression, as well as promoting pain transmission pathways. We will conclude by considering the therapeutic potential of treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.
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PMID:Mast cells, glia and neuroinflammation: partners in crime? 2403 75

The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.
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PMID:Complex disease and phenotype mapping in the domestic dog. 2679 39