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)

The ontogeny and function of gut-associated-lymphoid tissue is known to be critically dependent on the beta7 integrin subfamily. We have investigated the development of intestinal inflammation and pathogen-specific protective immunity to enteric helminth infection in beta7 integrin knockout (KO) mice. During Trichinella spiralis infection of the small intestine there was a significant delay and reduction in the magnitude of intestinal eosinophilia and mastocytosis in the absence of P7 integrin, resulting in impaired host protection. Aberrant distribution of mast cells was also observed in the small intestine of infected KO mice. Adoptive transfer of primed wild-type mesenteric lymph node cells into T. spiralis-infected beta7 KO mice did not restore the intestinal mast cell response, suggesting that the defect in intestinal mastocytosis is due to the absence of beta7 expression on this population rather than an indirect consequence of reduced T cell numbers. In contrast, no impairment in leukocyte recruitment or protection against Trichuris muris infection of the large intestine was observed in KO mice. Taken together the data provide the first description of reduced leukocyte homing and attenuated protective immunity against helminth infection in beta7 KO mice. Furthermore, these results suggest that beta7 integrin-independent adhesion molecule interactions are deployed in the large but not small intestine during intestinal inflammation.
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PMID:Beta7 integrin-deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminth infection. 1089 2

The association of mast cells and lymphoid tissues may reflect either regional overproduction of growth factors for mast cells or a predisposition for mast cells at certain sites within the body, particularly the liver, lymph nodes, and spleen. The significant increase in mast cell number associated with mastocytosis is not sufficient to generate a change in either T-cell or B-cell functions, as evaluated by analyzing cytokine phenotype or immunoglobulin production, respectively, nor to expose these patients to infections or allergic diseases. Mast cells in mastocytosis cannot be said with certainty to be "normal" in all respects, however, and the failure to identify an effect of mast cells on either B-cell Ig production or T-cell cytokine profiles cannot be taken as absolute evidence that mast cell products have no influence on lymphocyte function, particularly at the local tissue level.
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PMID:Lymphoid tissues and the immune system in mastocytosis. 1090 41

The deleterious effects of ultraviolet B radiation (UVR) on cutaneous immunity are mediated in part by cytokines released from cutaneous cells following radiation exposure. On the one hand, TNF-alpha has been advocated as the primary mediator of failed contact hypersensitivity induction, and, on the other hand, IL-10 has been held responsible for tolerance. While keratinocytes exposed to UVR have been found to produce both TNF-alpha and IL-10, there is reason to question whether these major cellular constituents of the epidermis are the relevant source of immunomodulatory cytokines after UVR. Dermal mast cells also produce TNF-alpha and IL-10, and we have recently reported that mast cell-derived TNF-alpha is required for UVR-induced impairment of CH induction. In this study, we have examined whether mast cells are also a relevant source of IL-10 in UVR-dependent tolerance. We found that (a) UVR fails to induce tolerance in mast cell-deficient mice, and (b) that tolerance occurs if mast cells are triggered to degranulate after ligation of the IgE receptor. Both types of tolerance were neutralized with anti-IL-10 antibodies, are hapten specific, and are associated with regulatory lymphoid cells. We conclude that mast cells are required in UVR-induced tolerance and may be one of the major sources of IL-10 that mediates the tolerance induced by acute, low-dose UVR.
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PMID:Hapten-specific tolerance induced by acute, low-dose ultraviolet B radiation of skin requires mast cell degranulation. 1138 18

The dual specificity kinases mitogen-activated protein kinase (MAPK) kinase (MKK)7 and MKK4 are the only molecules known to directly activate the stress kinases stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) in response to environmental or mitogenic stimuli. To examine the physiological role of MKK7 in hematopoietic cells, we used a gene targeting strategy to mutate MKK7 in murine T and B cells and non-lymphoid mast cells. Loss of MKK7 in thymocytes and mature B cells results in hyperproliferation in response to growth factor and antigen receptor stimulation and increased thymic cellularity. Mutation of mkk7 in mast cells resulted in hyperproliferation in response to the cytokines interleukin (IL)-3 and stem cell factor (SCF). SAPK/JNK activation was completely abolished in the absence of MKK7, even though expression of MKK4 was strongly upregulated in mkk7(-/-) mast cell lines, and phosphorylation of MKK4 occurred normally in response to multiple stress stimuli. Loss of MKK7 did not affect activation of extracellular signal-regulated kinase (ERK)1/2 or p38 MAPK. mkk7(-/-) mast cells display reduced expression of JunB and the cell cycle inhibitor p16INK4a and upregulation of cyclinD1. Reexpression of p16INK4a in mkk7(-/-) mast cells abrogates the hyperproliferative response. Apoptotic responses to a variety of stimuli were not affected. Thus, MKK7 is an essential and specific regulator of stress-induced SAPK/JNK activation in mast cells and MKK7 negatively regulates growth factor and antigen receptor-driven proliferation in hematopoietic cells. These results indicate that the MKK7-regulated stress signaling pathway can function as negative regulator of cell growth in multiple hematopoietic lineages.
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PMID:The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor receptor-induced proliferation in hematopoietic cells. 1156 Sep 92

By using a serial analysis of gene expression (SAGE), we have identified a novel full-length cDNA that is preferentially expressed in human cord blood-derived mast cells. The predicted protein showed unique primary structure with a nuclear localization signal (NLS), a sterile alpha motif (SAM), and a Src homology 3 domain (SH3) (termed Nash1). Nash1 was mapped to human chromosome 21q11.1 and highly expressed in spleen, liver, peripheral blood, and mast cell lines. In consistent with the presence of NLS, Nash1 was localized in the nucleus. Interestingly, screening gene databases for Nash1-related sequences revealed the existence of a Nash1-related gene termed SLY that was preferentially detected in lymphoid cells. We also found at least two additional candidates for this gene family in the database. These findings suggested that Nash1 and Nash1-related proteins consisted of a novel family of signaling/adaptor proteins, and Nash1 might function as a signaling component of mast cells, possibly in the nucleus.
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PMID:Identification of Nash1, a novel protein containing a nuclear localization signal, a sterile alpha motif, and an SH3 domain preferentially expressed in mast cells. 1159 64

The sonographic findings in 101 cats with splenic abnormalities are presented. Diagnosis was made by ultrasound-guided fine needle aspirate or fine-needle biopsy (n = 91), ultrasound-guided core biopsy (n = 1), surgical core biopsy (n = 1), or necropsy (n = 10). Two cats had more than one diagnostic procedure (fine needle aspirate and necropsy or core biopsy and necropsy). The splenic abnormalities included lymphosarcoma (n = 30), mast cell tumor (n = 27), extramedullary hematopoiesis and/or lymphoid hyperplasia (n = 27), epithelial tumors (n = 6), mesenchymal tumors (n = 4), malignant histiocytosis (n = 2), myeloproliferative disease (n = 2), pyogranulomatous inflammation (n = 2), erythroleukemia (n = 1), eosinophilic syndrome (n = 1), hematoma (n = 1), and granulomatous splenitis (n = 1). Three cats had more than one splenic abnormality (mast cell tumor and metastatic carcinoma, pyogranulomatous inflammation and lymphoid hyperplasia, histiocytic lymphosarcoma, and lymphoid hyperplasia). Pathognomonic changes were not seen for any of the diseases.
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PMID:Ultrasonographic appearance of splenic disease in 101 cats. 1167 67

This review discusses experimental evidences that indicate the IgE participation on the effector mechanisms that leads to gastrointestinal nematode elimination. Data discussed here showed that, for most experimental models, the immune response involved in nematode elimination is regulated by Th-2 type cytokines (especially IL-4). However, the mechanism(s) that result in worm elimination is not clear and might be distinct in different nematode species. Parasite specific IgE production, especially the IgE produced by the intestinal mucosae or associated lymphoid organs could participate in the intestinal elimination of Trichinella spiralis from infected rats. Intestinal IgE may also be important to the protective mechanism developed against other gastrointestinal nematodes that penetrate the murine duodenum mucosa tissue, such as Strongyloides venezuelensis and Heligmosomoides polygyrus. At least in Trichinella spiralis infected rats, the results indicated that intestinal IgE might work independently from mast cell degranulation for worm elimination.
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PMID:Importance of immunoglobulin E (IgE) in the protective mechanism against gastrointestinal nematode infection: looking at the intestinal mucosae. 1169 54

The REAL Classification of lymphomas, proposed in 1994, represents a new paradigm in lymphoma classification, consisting of a list of biologic entities defined by clinicopathologic and immunogenetic features. The non-Hodgkin's lymphomas comprise precursor lymphoblastic and mature cell neoplasms of B, T or putative natural killer cell lineage. An individual entity can exhibit a range of morphologic appearances and a range of clinical behavior. The categories in Hodgkin's lymphomas are identical to the widely used Rye classification except for the additional of a new category termed 'lymphocyte-rich classical Hodgkin's lymphoma'. The REAL classification has been validated by a major multi-institutional study involving 1378 cases (The Non-Hodgkin's Lymphoma Classification Project), showing that it is both reproducible and clinically relevant. The new World Health Organization classification of hematopoietic and lymphoid tumors, to be published in 2001, is a joint project of the Society for Hematopathology and European Association of Hematopathologists, under the auspices of the World Health Organization. This classification includes not only lymphoid neoplasms, but also myeloid, histiocytic and mast cell neoplasms. The lymphoma component of the classification is merely an update of the REAL classification, with minor changes necessitated by new information that has become available since its proposal. A conceptual grouping of the non-Hodgkin's lymphomas into four categories (indolent, aggressive, highly aggressive, and localized indolent) is also presented in this review. The next major impetus influencing the approach to lymphoma classification will no doubt be molecular genetics, in particular DNA microarrays, which will yield an enormous amount of new data that will aid in the understanding of lymphomas.
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PMID:The new World Health Organization classification of lymphomas: the past, the present and the future. 1175 90

A family with multiple gastrointestinal stromal tumors (GISTs), a new type of germline mutation of KIT gene, and dysphagia is reported. The mutation was observed at Asp-820 in tyrosine kinase (TK) II domain. Mutations in TK II domain have been found in mast cell and germ cell tumors but not in GISTs, and the present family members are the first reported cases of GISTs with TK II domain mutations, including sporadic GISTs. Because interleukin 3-dependent Ba/F3 murine lymphoid cells transfected with the mutant KIT complementary DNA grew autonomously without any growth factors and formed tumors in nude mice, the mutation was considered to be gain-of-function type. Family members with the germline KIT mutation reported dysphagia, but those without the mutation did not. The mechanism of dysphagia was examined with gastrointestinal fiberscopy, endoscopic ultrasonography, and esophageal manometry. No mechanical obstruction was found, and the esophagus was not remarkably dilated. In the family members with dysphagia, endoscopic ultrasonography at the esophagocardiac junction showed a thickened hyperechoic layer between the circular and longitudinal muscle layers, suggesting hyperplasia of interstitial cells of Cajal at the myenteric plexus layer. Manometry showed low resting lower esophageal sphincter pressure and abnormal simultaneous contractions of the esophagus without normal peristalsis. These findings indicate that the dysphagia of the present family is different from typical achalasia. This is the first report of familial dysphagia caused by germline gain-of-function mutation of the KIT gene at the TK II domain.
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PMID:Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene. 1198 33

Neoplasia is common in pet dogs but accurate figures for the incidence of tumours in this, as in other species, are sparse. The purpose of this study was to document the occurrence of tumours in a defined population of dogs. From a database of 130,684 insured dogs, claims relating to the investigation or treatment of tumours or tumour-like lesions during a 12-month period were accessed and followed up. A total of 2,546 claims were tumour related and were classified according to tumour site and type. Because the demographics of the insured population were skewed towards younger animals, a standard population, as described in the veterinary literature, was used in the calculation of tumour incidence rates. The skin and soft tissues were the most common sites for tumour development, with a standardised incidence rate of 1,437 per 100,000 dogs per year, followed by alimentary (210), mammary (205), urogenital (139), lymphoid (134), endocrine (113) and oropharyngeal (112). Canine cutaneous histiocytoma was the most common single tumour type, with a standardised incidence rate of 337 per 100,000 dogs per year, followed by lipoma (318), adenoma (175), soft tissue sarcoma (142), mast cell tumour (129) and lymphosarcoma (114). These data are unique and provide a valuable basis for future research into the aetiology and epidemiology of canine tumours.
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PMID:Canine neoplasia in the UK: estimates of incidence rates from a population of insured dogs. 1207 88


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