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)

Mastocytosis gives rise to clinical symptoms such as flushing, itching and diarrhoea. We report a patient with urticaria pigmentosa without evidence of systemic involvement but with recurrent episodes of diarrhoea. The patient had elevated circulating levels of calcitonin, which might have been a mediator of her diarrhoea. We suggest that serum calcitonin level should be checked in patients with mast cell disease and diarrhoea.
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PMID:Hypercalcitoninaemia in a patient with urticaria pigmentosa. A possible cause of diarrhoea. 673 Oct 41

The effects of the specific active cancer immunotherapy utilizing autologous tumor tissue particles polymerized with ethylchlorformiate on the immune system of the host were evaluated in DBA/2 mice bearing a malignant mast cell tumor, mastocytoma (P-815 X 2), with the special emphasis placed on the morphologic changes in the lymph nodes. In assessing the lymph node morphology in relation to the immunologically reactive lymphocyte populations (T- and B-cells), the standardized reporting system was employed, and the post-capillary venule score (PCV-S), shown to be related to the T-cell activity, was calculated for each lymph node. The specific cancer immunotherapy instituted along with the PPD tuberculin as adjuvant was capable of reverting to a considerable degree the profound depletion of the T-cell population in the paracortex of the lymph nodes, as well as exerting a stimulatory influence on the B-cells responsible for antibody synthesis in the cortex and medulla of the nodes. The results were interpreted to favor the view that the favorable influence on the tumor rejection previously shown to be exerted by the specific immunotherapy technique studied, most probably is attributable to the observed stimulatory effects of it on the lymphocyte populations involved in cell-mediated and humoral immune responses. The appropriate cooperation of both T- and B-lymphocytes is most probably needed to ensure the most effective host response against the tumor cells in this system.
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PMID:Immunological reactivity in the lymph nodes of the host following experimental cancer immunotherapy utilizing polymerized autologous tumor tissue particles. 677 10

Mastocytosis is a disease in which the mast cell population is increased in various tissues. Although the mechanism for the increased density of mast cells is not understood, recent research into mast cell structure and function has improved our understanding of the symptomatology and prompted newer and better approaches to treatment. To be discussed, and of particular interest to the dermatologist, is the management of, and evaluation for, systemic disease in a patient presenting with cutaneous findings.
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PMID:Mastocytosis and the mast cell. 717 10

A xenoantiserum raised against a mast cell tumor line (FMP1.1) was found to have cross-reactivity with surface antigens on primitive hemopoietic precursor cells in normal mouse bone marrow: erythroid burst-forming units; granulocyte-macrophage colony-forming cells; and high-proliferative-potential granulocyte-macrophage colony-forming cells. In the presence of anti-FMP1.1 serum and complement, only 15 +/- 2% (S.E.) (n = 5) of normal nucleated marrow cells were lysed, demonstrating that the majority of mature hemopoietic cells did not express the antigens detected on their primitive counterparts. A variety of hemopoietic and other tumor cell lines were examined with anti-FMP1.1 serum, and all B- and pre-B-lymphomas, one plasmacytoma, one mastocytoma, and a monocyte-macrophage line exhibited significant lysis. Direct typing of the FMP1.1 tumor demonstrated that it did not express the B-cell surface antigens such as Ia, surface immunoglobulin, Fc, and complement (C3) receptors. Although the Ly.6 alloantigen was present on FMP1.1 cells, this antigen was not found on marrow erythroid burst-forming units and granulocyte-macrophage colony-forming units. Absorption of anti-FMP1.1 serum with cross-reacting (WEHI-3 and W-279.1) and a nonreacting (P-815) cell line confirmed the specificity of the antiserum reaction with these cells and marrow progenitors. These experiments indicated that more than one antibody is contained in anti-FMP1.1 serum. Thus, the mast cell tumor (FMP1.1) carries an unusual array of antigens, which are found on bone marrow progenitors and are not expressed on the majority of differentiated cells. It has been demonstrated that tumor cell lines provide an important basis for the analysis of surface membrane antigens expressed on normal hemopoietic progenitors.
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PMID:Surface membrane antigens of hemopoietic tumor cell lines and normal marrow progenitor cells. 728 8

Both stem cells and mast cells express c-kit and proliferate after exposure to c-kit ligand. Mutations in c-kit may enhance or interfere with the ability of c-kit receptor to initiate the intracellular pathways resulting in cell proliferation. These observations suggested to us that mastocytosis might in some patients result from mutations in c-kit. cDNA synthesized from peripheral blood mononuclear cells of patients with indolent mastocytosis, mastocytosis with an associated hematologic disorder, aggressive mastocytosis, solitary mastocytoma, and chronic myelomonocytic leukemia unassociated with mastocytosis was thus screened for a mutation of c-kit. This analysis revealed that four of four mastocytosis patients with an associated hematologic disorder with predominantly myelodysplastic features had an A-->T substitution at nt 2468 of c-kit mRNA that causes an Asp-816-->Val substitution. One of one patient examined who had mastocytosis with an associated hematologic disorder had the corresponding mutation in genomic DNA. Identical or similar amino acid substitutions in mast cell lines result in ligand-independent autophosphorylation of the c-kit receptor. This mutation was not identified in the patients within the other disease categories or in 67 of 67 controls. The identification of the point mutation Asp816Val in c-kit in patients with mastocytosis with an associated hematologic disorder provides insight not only into the pathogenesis of this form of mastocytosis but also into how hematopoiesis may become dysregulated and may serve to provide a means of confirming the diagnosis, assessing prognosis, and developing intervention strategies.
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PMID:Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. 747 40

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in hematopoiesis, especially in mast cell growth and differentiation. Although a number of dominant loss-of-function mutations of c-kit gene have been well characterized in mice, rats, and humans, little is known about the c-kit mutations contributing to ligand-independent activation of the c-kit receptor tyrosine kinase (KIT). In a murine mastocytoma cell line, P-815, KIT has been found to be constitutively phosphorylated on tyrosine and activated in a ligand-independent manner. Sequencing of the whole coding region of c-kit cDNA showed that c-kit cDNA of P-815 cells carries a point mutation in codon 814, resulting in amino acid substitution of Tyr for Asp. Murine wild-type c-kit cDNA and mutant-type c-kit cDNA encoding Tyr in codon 814 were expressed in cells of a human embryonic kidney cell line, 293T. In the transfected cells, mutant-form KITTyr814 was strikingly phosphorylated on tyrosine and activated in immune complex kinase reaction regardless of stimulation with a ligand for KIT (stem cell factor), whereas tyrosine phosphorylation and activation was barely detectable in wild-form KIT. The data presented here provide evidence for a novel activating mutation of c-kit gene that might be involved in neoplastic growth or oncogenesis of some cell types, including mast cells.
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PMID:Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation. 751 8

The c-kit protooncogene encodes a receptor tyrosine kinase that mediates signals required for differentiation, proliferation and survival of mast cells. We have already shown the constitutive activation of c-kit receptor tyrosine kinase (KIT) in a human mast cell leukemia line (HMC-1) and a murine mastocytoma cell line (P-815). We here examined whether such constitutive activation of KIT occurred in the rat tumor mast cell line RBL-2H3 as well, which is frequently used as a tool for studying functions of mast cells. In RBL-2H3 cells, KIT was constitutively phosphorylated on tyrosine and activated in the absence of autocrine production of its ligand, stem cell factor (SCF). Sequencing analysis revealed that one of c-kit genes of RBL-2H3 cells had a point mutation, resulting in amino acid substitution of Tyr for Asp in codon 817. When rat wild-type c-kit cDNA and mutant-type c-kit cDNA encoding KITTyr817 were transfected into cells of a human embryonic kidney cell line (293T), only mutant form KITTyr817 was constitutively phosphorylated on tyrosine and activated in the absence of SCF. Since mutations at the same Asp codon constitutively activated KIT in all the human HMC-1, murine P-815, and rat RBL-2H3 cell lines, and since the incorporation of antisense oligonucleotides of c-kit messenger RNA significantly suppressed the proliferation of RBL-2H3 cells, the activating mutations in the Asp codon of the c-kit gene appeared to be involved in neoplastic growth of mast cells.
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PMID:Substitution of an aspartic acid results in constitutive activation of c-kit receptor tyrosine kinase in a rat tumor mast cell line RBL-2H3. 753 1

Mastocytosis is a disease of mast cell hyperplasia that may involve several organ systems, including liver. Between 1988 and 1991, we conducted a retrospective-prospective study of 41 patients with mastocytosis and found 61% had evidence of liver disease. Hepatomegaly was detected in 24%, splenomegaly in 41%, and elevated serum alkaline phosphatase, serum aminotransaminases, 5'nucleotidase, or gamma-glutamyltranspeptidase (GGTP) in 54% of the patients. Alkaline phosphatase levels directly correlated with GGTP levels, hepatomegaly, splenomegaly, and liver mast cell infiltration and fibrosis. Elevated alkaline phosphatase levels and splenomegaly were observed more frequently in patients with categories II and III mastocytosis. Five patients in combined disease categories II or III developed ascites or portal hypertension and died of complications of mastocytosis; three had hypoprothrombinemia at the time of death. Thirty-five liver biopsy specimens from 25 patients were examined. Mast cell infiltration was commonly observed in the biopsy specimens, more severe in those patients with either category II or III disease, and correlated with hepatomegaly, splenomegaly, alkaline phosphatase levels, and GGTP levels. Mast cells were often only detected by using special stains (toluidine blue and chloracetate esterase). Increased portal fibrosis was seen in 68% of the biopsy specimens and correlated with mast cell infiltration and portal inflammation. Cirrhosis was not observed. Nodular regenerative hyperplasia, portal venopathy, and venoocclusive disease was observed in eight biopsy specimens and may have been the cause of the portal hypertension or ascites in four patients. These findings demonstrate that liver disease with mast cell infiltration is a common finding in patients with mastocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases. 755 67

In an effort to identify genes that are differentially regulated during mast cell development, subtracted cDNA prepared from wild-type murine P815 mastocytoma cells and a P815 subline that exhibits properties of mast cell differentiation was used to screen mast cell cDNA libraries. Several known mast cell-specific cDNAs were isolated including mast cell carboxypeptidase A (MC-CPA), murine mast cell protease-5 (MMCP-5), and gp49. A novel cDNA, designated Tbc1, was identified that showed differential expression in the two mast cell lines. The amino acid sequence predicted from the cDNA contains a 200 amino acid domain that is homologous to regions in the tre-2 oncogene and the yeast regulators of mitosis, BUB2 and cdc16. The N-terminal region contains a number of cysteine and histidine residues, potentially encoding a zinc finger domain. Tbc1 is a nuclear protein and is expressed in highest levels in hematopoietic cells, testis and kidney. Within these tissues, expression of Tbc1 is cell- and stage-specific. Based on sequence similarity, pattern of expression and subcellular localization, Tbc1 may play a role in the cell cycle and differentiation of various tissues.
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PMID:Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16. 756 74

A rapid and continuous proteolysis of tryptophan hydroxylase was demonstrated with two mast cell lines derived from rat basophilic leukemia cells (RBL2H3) and mouse mastocytoma (FMA3). Under conditions in which protein biosynthesis was arrested by administration of cycloheximide, the decay profile of tryptophan hydroxylase protein was traced by Western blot analysis. Incorporation of [35S]methionine and the chase experiment performed without interfering with the metabolic stage also showed that tryptophan hydroxylase had been cleaved rapidly. The half life of the enzyme was 11-15 min in RBL2H3 cells and 40-60 min in FMA3 cells, and the process was demonstrated to be dependent on intracellular ATP.
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PMID:Rapid turnover of tryptophan hydroxylase in serotonin producing cells: demonstration of ATP-dependent proteolytic degradation. 761 72


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