Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

Systemic mastocytosis (SM) are defined by an abnormal growth and accumulation of mast cells in bone marrow and/or other extracutaneous organs. There is currently no cure for this disease. Because of similarities and/or association of mastocytosis with myeloproliferative disorders, interferon alpha has been tested but with contradictory reported results. A first prospective multicenter phase II trial was then started in France. From 1994 to 1997, 20 adult patients with confirmed bone marrow involvement received interferon alpha-2b for at least 6 months, (from 1 million U per day up to 5 million U/m(2)/day). Thirteen patients who presented systemic and/or specific cutaneous manifestations, demonstrated objective responses: seven (35%) were partial, six (30%) minor but no complete response could be observed at the time of analysis. The bone marrow remained unchanged in 12/13. Thus, interferon should be offered to patients with severe systemic manifestations, who have not responded to symptomatic therapies, even in case of non-aggressive mastocytosis, with or without corticosteroids the first weeks. Long-term therapy should be offered to patients with initial positive response. To control more aggressive SM or mastocytosis associated with clonal hematologic non-mast cell lineage or leukaemia mast cell, other chemotherapeutic regimens should be proposed like Cladribine (2-chlorodeoxyadenosine, 2-CDA) or polychemotherapies including interferon as it is being tested in France in a new multicentric protocol, coordinated by the association AFIRMM, with interferon and oral cytarabine.
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PMID:Interest of interferon alpha in systemic mastocytosis. The French experience and review of the literature. 1521 17

Mast cell leukemia (MCL) is a rare form of aggressive mastocytosis with a reported median survival below 6 months. Casuistic reports suggest the effectiveness of allogeneic bone marrow transplantation (BMT) for MCL. However, these reports lack clear evidence for a graft-versus-mast-cell (GvMC) effect. We prospectively investigated the GvMC at different time points after allogeneic BMT and donor-lymphocyte infusions (DLI). Samples were gathered from a patient with MCL treated with allogeneic BMT from an unrelated HLA identical donor. Parameters for detection of a GvMC effect included flow cytometrical analysis of mast cell (MC) populations in peripheral blood and BM, BM smear and histology, chimerism analysis of flow cytometrically sorted BM CD117+/CD34- MC and testing for anti-mast cell reactivity of donor lymphocytes by interferon (IFN)-gamma ELISPOT. DLIs reduced MC from 5 to 0.5%. MC chimerism analysis demonstrated a complete recipient genotype after BMT, suggesting that the persistent mastocytosis was part of residual neoplastic disease. At 3.7 years after BMT, there is some evidence for relapse. In summary, BMT and DLIs attenuated the mastocytosis from an aggressive to an indolent form and may have improved the patients' prognosis. The in vitro data of our study indicate for the first time the existence of a GvMC effect.
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PMID:Evidence for a graft-versus-mast-cell effect after allogeneic bone marrow transplantation. 1527 11

Daily treatment of systemic mastocytosis with high-dose interferon-alfa often is not tolerated because of clinical or hematologic side effects. We report successful treatment of a patient with systemic mastocytosis, who was positive for the D816V mutation, with interferon alfa-2b at 10 million units three times per week. During 5 years of treatment, bone marrow infiltration by mast cells decreased from 50 to < or =5%, and there was a decrease (urinary N-methylhistamine excretion, 75%; serum tryptase concentration, 98%) or normalization (serum calcitonin value, urinary prostaglandin F2alpha excretion) of mast cell mediators. Side effects included mild depression (untreated) and biochemical hypothyroidism easily managed with supplemental levothyroxine.
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PMID:Successful treatment of systemic mastocytosis with high-dose interferon-alfa: long-term follow-up of a case. 1560 59

DNA microarray hybridization was used to measure the changes of mRNA levels over time during the development of delayed pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De. Upregulation of a number of interferon (IFN)-gamma-stimulated genes was detected in delayed pigmented lesions, suggesting that IFN-gamma may play a pivotal role in the development of delayed pigmented spots in this model. Upregulation of these genes was further supported by the increased protein expression level of IFN-gamma in the lesions. Epidermal infiltration of CD8(+) T lymphocytes and mast cell accumulation in the dermis were observed in delayed pigmented spots. Genes encoding chemokines such as monocyte chemoattractant protein-2 (MCP-2), IFN-inducible protein 10 (IP-10), and monokine induced by IFN-gamma (MIG) were among those upregulated by IFN-gamma. We hypothesize that chemokines produced in the epidermis induce migration of inflammatory cells, such as T lymphocytes, mast cells, and macrophages, to the vicinity of melanocytes. Keratinocytes, T lymphocytes, mast cells, and macrophages would become involved in an interactive network, providing a suitable local environment for melanocyte activation. In this environment, melanocytes are exposed to an extensive array of secreted mediators. Reciprocal activation among these cells to maintain this interactive network results in constitutive melanocyte activation and chronic melanin synthesis in delayed pigmented lesions.
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PMID:Upregulation of the IFN-gamma-stimulated genes in the development of delayed pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De. 1585 48

Systemic mastocytosis is characterized by abnormal mast cell proliferation in different organs. The 2001 consensus classification distinguishes in separate categories indolent systemic mastocytosis, systemic mastocytosis with concomitant blood disease, aggressive systemic mastocytosis and mast cell leukemia. Clinical manifestations are caused by tissue infiltration by proliferating mastocytes and by release of mediators. The principal organs affected are the skin, bones, digestive tract, liver, spleen and lymph nodes. Diagnosis of mastocytosis is based on appropriate stains (Giemsa, toluidine blue) and immunophenotype features (tryptase, CD117, also known as c-KIT and stem cell factor receptor). Serum tryptase levels reflect the total mast cell burden. Treatment must prevent release of mast cell mediators (histamine antagonists, cromolyn sodium, corticosteroids, or leukotriene-receptor inhibitors), limit bone involvement (bisphosphonates) and reduce the number of circulating mast cells (interferon, cladribine, or tyrosine kinase inhibitors). Enhanced understanding of the pathogenic mechanisms (mutation of c-kit and platelet-derived growth factor receptor alpha has led to the development of targeted treatments, including new inhibitors of tyrosine kinase and of nuclear factor Kappa B.
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PMID:[Systemic mastocytosis]. 1598 48

Systemic mastocytosis is characterized by mast cell proliferation in different organs. Classification delineates 4 categories: indolent systemic mastocytosis, systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease, aggressive systemic mastocytosis and mast cell leukaemia. Clinical manifestations are due to organ infiltration (skin, bone, gut, liver, spleen, lymph nodes) and release of mast-cell mediators. Diagnosis of mastocytosis is based on appropriate stains (Giemsa, Toluidine) and immunophenotype features (tryptase, CD117). Serum level of tryptase reflects the total burden of mast cells. Treatment must prevent mast cell mediators release (histamine antagonists, cromolyn sodium, corticosteroids, leukotriene-receptor inhibitors) and have a cytoreductive effect (interferon, cladribine, tyrosine kinase inhibitors).
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PMID:[Systemic mastocytosis]. 1633 97

A 64-year-old man was diagnosed as having urticaria pigmentosa in 1998, and treated with PUVA therapy. In January 2002, X-ray imaging revealed osteosclerosis was detected in the systemic bone and bone scintigraphy. A bone marrow aspiration sample was not obtained due to a dry tap. CT scans showed hepatosplenomegaly and mesenteric lymphadenopathy. Myelofibrosis and diffuse mast cell infiltration were revealed by a bone marrow biopsy, and a diagnosis of systemic mastocytosis with severe osteosclerosis and myelofibrosis was made. In October 2003, he was admitted to our hospital because of mid back pain. A neurological examination showed muscle weakness in the upper and lower limbs, sensory disturbance below the level of Th4 and urinary obstruction. T1 and T2 weighted images of MRI demonstrated a high intensity epidural mass lesion extending from the vertebral level of C5 to Th2 and severely compressing the spinal cord. We considered the possibility of the invasion of the spinal canal by the mastocytosis. The patient was treated with interferon alpha-2b (IFN-alpha2b) and prednisolone. Subsequently, the motor and sensory disturbances were gradually alleviated, and spinal MRI confirmed a marked reduction in the size of the epidural tumor. However, the patient became resistant to interferon, and died of multiple organ failure in spite of steroid pulse and cladribine therapies. Multiple organ infiltration by mast cells was revealed at autopsy.
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PMID:[Case of intraspinal epidural tumor developing after systemic mastocytosis with marked osteosclerosis and myelofibrosis]. 1644 Jul 79

Mice experimentally infected with H. nana and injected with immunosuppressant {cyclophosphamide (Cp) and lead nitrate (Ln)} showed significant increase in infection intensity, significant decrease in intestinal mast cell count, dissemination of larvae to the liver, toxic hepatitis and absence of specific serum IgG. Cyclophosphamide caused morphological abnormallities in adult worms, prolongation of patent period and more severe villous changes. Immuno-stimulants represented by Levamisol (Lv) and gamma interferon (IFN-alpha) caused significant decrease in infection intensity, significant shortening of patent period and early improvement of histopathological changes. Immunostimulants, particularly IFN-alpha, were highly effective in counteracting hyperinfection seen with immuno-suppression. The study confirmed the deleterious effects of immunosuppression on hymenolepiasis and suggested a beneficial role for immunotherapy for immunosuppressed patients.
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PMID:Effect of some immunomodulators on the host-parasite system in experimental Hymenolepiasis nana. 1660 1

Interleukin-12 (IL-12), a heterodimeric cytokine (p35/p40) produced mainly from macrophages and dendritic cells, is an important regulator of T-helper 1 cell responses and for host defense. We found that interferon (IFN) consensus sequence binding protein (ICSBP), which is a transcription factor essential for the expression of p40, was expressed in mouse bone marrow-derived mast cells (BMMCs). The transcription levels of p35 and p40 were increased by stimulation of BMMCs with IFN-gamma/lipopolysaccharide (LPS). IL-12 was secreted from BMMCs in response to LPS but not by FcepsilonRI cross-linking. The p40 levels in the peritoneal cavity of mast cell-deficient W/W(v) and W/W(v) reconstituted with p40(-/-) BMMCs were significantly lower than those of WBB6F(1)(+/+) and wild-type (WT) BMMC-reconstituted W/W(v) in the acute septic peritonitis model. The survival rate of W/W(v) reconstituted with p40(-/-) BMMCs was significantly decreased compared to those of WBB6F(1)(+/+) and WT-BMMC-reconstituted W/W(v), which was due to reduced production of IFN-gamma and subsequent impaired activation of neutrophils in the peritoneal cavity. Survival rate of p40(-/-) mice was also restored by adoptive transfer of WT-BMMCs. These results demonstrate that mast cells play a significant role in the production of IL-12 required for host defense. This is the first report to demonstrate that mast cells are a crucial source of functional IL-12.
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PMID:Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections. 1728 16


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