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: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocytes activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.
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PMID:Biochemical diagnosis of systemic mast cell disorders. 200 47

Systemic mast cell disease/mastocytosis (SMCD) is best defined as a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells (TMC). SMCD preferentially involves the bone marrow, skin, spleen, liver, and lymph nodes. The histopathological diagnosis of SMCD may be very difficult to make, and the disease is often not considered in the differential diagnosis of lymphoreticular neoplasia. In suspected cases of SMCD, basic dyes such as Giemsa and toluidine blue are useful to demonstrate the specific metachromatic granules of TMC. The naphthol AS-D chloroacetate esterase reaction has also proved to be very reliable for enzyme-histochemical identification of TMC. Major diagnostic problems may arise in cases of malignant or "aggressive" SMCD exhibiting tissue infiltrates consisting predominantly of highly atypical, non-metachromatic TMC, which are usually also only weakly reactive for chloroacetate esterase. Immunostaining with antibodies against the mast cell-specific proteases tryptase and chymase has proved to be of great value of establishing the correct diagnosis in such cases. Anti-tryptase antibodies have major diagnostic significance due to their extremely high sensitivity and specificity. The classification of SMCD is controversial, but there is increasing support for the differentiation of at least two major subtypes that differ in prognosis: (i) a benign or "indolent" variant in which skin involvement (urticaria pigmentosa-like skin lesions) is usual, but associated malignant hematological disorders are rare; and (ii) a malignant or "aggressive" variant where skin involvement is usually absent but concomitant malignant hematological disorders (myelodysplastic and myeloproliferative syndromes and acute non-lymphocytic leukemias) are very common. Preliminary molecular biological studies of a few cases of malignant SMCD using the recently developed HUMARA assay have yielded evidence that the disease is monoclonal.
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PMID:Systemic mast cell disease (mastocytosis). General aspects and histopathological diagnosis. 930 69

The term "mastocytosis" is used to describe a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs). Cutaneous and systemic variants exist. Systemic mastocytosis may show an indolent or malignant clinical course. In malignant mastocytosis (MM), the diagnosis often is missed because the MCs are morphologically abnormal and lack metachromatic granules or the underlying histologic picture is complex. The cytoplasmic serine protease tryptase is produced by MCs and is thought to be expressed at all stages of MC maturation. To assess the diagnostic value of tryptase staining in mastocytosis, tissue sections from 93 patients with mastocytosis, including MM (n = 37), systemic indolent mastocytosis (n = 47), urticaria pigmentosa (n = 5), MC leukemia (n = 2), and solitary skin mastocytoma (n = 2) were stained with the antitryptase antibody G3. The results were compared with those of Giemsa and chloroacetate esterase (CAE) staining. Using antitryptase antibody G3, MC infiltrates were identified in all patients examined, including those with MM (37 of 37), and virtually all the neoplastic MCs (> 95%) appeared to react with G3. In MM, significantly fewer MCs were positive in Giemsa (54.5%; p < 0.05) and CAE (78.8%; p < 0.05). Moreover, G3 produced clear diagnostic staining in all cases of MM, but the proportion of cases with clear diagnostic results (> 10% of neoplastic cells positive) was considerably lower with Giemsa (48.6%; p < 0.05) and CAE (75.7%; p < 0.05) staining. By contrast, tryptase, Giemsa, and CAE produced diagnostic staining of MCs in virtually all cases of systemic indolent mastocytosis, urticaria pigmentosa, and solitary skin mastocytoma. In systemic mastocytosis, survival was significantly reduced in cases with Giemsa-/tryptase+ or CAE-/tryptase+ tumor cells compared to those cases with Giemsa+ or CAE+ MC infiltrates (p < 0.001).
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PMID:Diagnostic value of immunostaining for tryptase in patients with mastocytosis. 973 47

Systemic mastocytosis is a disease of mast cell proliferation that may be associated with hematologic disorders. There are no features on examination that allow the diagnosis of systemic disease, and mast cell-derived mediators, which may be elevated in urine or blood, may also be elevated in individuals with severe allergic disorders. Thus, the diagnosis usually depends on results of bone marrow biopsy. To facilitate evaluation, surrogate markers of the extent and severity of the disease are needed. Because of the association of mastocytosis with hematologic disease, plasma levels were measured for soluble KIT (sKIT) and soluble interleukin-2 receptor alpha chain (sCD25), which are known to be cleaved in part from the mast cell surface and are elevated in some hematologic malignancies. Results revealed that levels of both soluble receptors are increased in systemic mastocytosis. Median plasma sKIT concentrations as expressed by AU/mL (1 AU = 1.4 ng/mL) were as follows: controls, 176 (n = 60); urticaria pigmentosa without systemic involvement, 194 (n = 8); systemic indolent mastocytosis, 511 (n = 30); systemic mastocytosis with an associated hematologic disorder, 1320 (n = 7); aggressive mastocytosis, 3390 (n = 3). Plasma sCD25 levels were elevated in systemic mastocytosis; the highest levels were associated with extensive bone marrow involvement. Levels of sKIT correlated with total tryptase levels, sCD25 levels, and bone marrow pathology. These results demonstrate that sKIT and sCD25 are useful surrogate markers of disease severity in patients with mastocytosis and should aid in diagnosis, in the selection of those needing a bone marrow biopsy, and in the documentation of disease progression. (Blood. 2000;96:1267-1273)
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PMID:Soluble stem cell factor receptor (CD117) and IL-2 receptor alpha chain (CD25) levels in the plasma of patients with mastocytosis: relationships to disease severity and bone marrow pathology. 1094 67

Recent data suggest that angiogenesis in the bone marrow (BM) is augmented and associated with growth of neoplastic cells in various hematological malignancies. Systemic mastocytosis (SM) is a neoplasm affecting multilineage and mast cell (MC)-committed hemopoietic progenitors. In the present study, we have assessed the BM microvessel density (MVD) by CD34 immunohistochemistry in 21 patients with SM, 5 with cutaneous mastocytosis (no BM infiltrates), and 5 control cases (normal BM). The median BM MVD was significantly higher in SM compared to cutaneous mastocytosis or controls (P < 0.05). In addition, a significant correlation (r = 0.74) between the BM MVD and grade of MC infiltration (percent tryptase(+) BM infiltrates) was found in SM. Moreover, the MVD was higher in MC infiltrates compared to the nonaffected adjacent marrow (P < 0.05). Immunohistochemical staining revealed expression of vascular endothelial growth factor in MC infiltrates. The notion that SM is associated with increased BM angiogenesis and vascular endothelial growth factor expression may have implications for the biology of disease and development of new treatment strategies.
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PMID:Increased angiogenesis in the bone marrow of patients with systemic mastocytosis. 1200 Jul 16

Systemic mastocytosis is a disease defined by an abnormal infiltration of mast cells involving several extra-cutaneous organs. Hepatic involvement is frequent, however it rarely reveals the disease. We report two cases of systemic mastocytosis revealed by hepatic symptoms: liver failure in one case and jaundice in the second case. The diagnosis is often difficult. Mast cell tissular infiltration can be identified on paraffin sections by tryptase or CD117 (c-kit) immuno-staining.
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PMID:[Liver involvement revealing systemic mastocytosis: report of two cases]. 1504 7

Mastocytosis comprises several diseases characterized by an abnormal increase in tissue mast cells. Cutaneous mastocytosis (CM) is the most common form of mastocytosis, affects predominantly children, and presents as a mast cell hyperplasia limited to the skin. Systemic mastocytosis (SM) comprises multiple distinct entities in which mast cells in filtrate the skin and/or other organs. The diagnosis of SM is based on the presence of one major criterion and one minor criterion or three minor criteria. Major criteria include the presence of multifocal dense infiltrates of > 15 mast cells in bone marrow and/or other extracutaneous organs. Four minor criteria include the presence of elevated serum alpha-tryptase levels > 20 ng/mL, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, the presence of a c-kit mutations on bone marrow and/or other tissues mast cells, and the presence of > 25% abnormal spindle-shaped mast cells in bone marrow and/or tissues. Symptoms of CM include pruritus, flushing urticaria, and dermatographism. Symptoms of SM include cutaneous symptoms in association with syncope, gastric distress, nausea and vomiting, diarrhea, bone pain, and neuropsychiatric symptoms. Activating and nonactivating mutations of c-kit (Asp816Val) are seen in adult SM and in some pediatric CM (Gly839Lys), indicating a clonal dysregulation. There is no cure for mastocytosis but the majority of pediatric CM regress at puberty. Women with mastocytosis are fertile and pregnancy and delivery have been successful by blocking mast cell-mediated symptoms. Symptomatic treatment aimed at reducing the effect of mediators is effective with antihistamines and mast cell-stabilizing agents such as sodium cromolyn. To reduce mast cell burden, interferon alpha, steroids, and purine analogs have been used with varying results. Future directions include tyrosine kinase inhibitors and bone marrow transplant.
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PMID:Mastocytosis: classification, diagnosis, and clinical presentation. 1505 60

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

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocyte activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.
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PMID:Biochemical diagnosis of systemic mast cell disorders. 1679 4


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