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)

Human sarcolectin is known as growth promoter and interferon-alpha/beta antagonist. Besides N-acetylneuraminic acid-dependent cell agglutination it also binds to a macrophage migration inhibitory factor (MIF). Several types of negatively charged carbohydrates interfere with this binding, indicating importance of a negatively charged cluster. Since human serum albumin that has very similar properties in gel electrophoretic analysis can also bind to this factor with a comparatively reduced extent, sarcolectin and albumin are compared biochemically and immunologically. Their peptide maps, generated by cleavage with cyanogen bromide and N-chlorosuccinimide, reveal no differences. The N-terminal sequences are identical up to the fourteenth position that have unequivocally been determined. Reactivities to anti-human serum albumin antibody that inhibits binding of sarcolectin to MIF are similar. Fractionation of human albumin by chromatography on hydroxyapatite yields a subfraction with increased specific activity, measured by extent of inhibition of sarcolectin-MIF interaction. It exhibits the same inhibitory capacity as a similarly derived subfraction from sarcolectin. Interestingly, rabbit and pig serum albumins are as active as human albumin to inhibit binding of sarcolectin to MIF, whereas hamster, mouse, horse and bovine albumin preparations were ineffective up to 2.5 mg/ml. Thus, sarcolectin appears to be a subfraction of human serum albumin whose functionally relevant molecular peculiarities are presently unknown. Neither treatment with organic solvents nor with lipases, but exposure to trypsin, chymotrypsin and pronase can impair sarcolectin's ability to bind MIF.
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PMID:Migration inhibitory factor-binding sarcolectin from human placenta is indistinguishable from a subfraction of human serum albumin. 798 Aug 71

Four patients with systemic mastocytosis, two men and two women, are presented. Three of them (patients 1, 2, and 4) developed portal hypertension and ascites without histological evidence of cirrhosis in liver biopsy. The remaining patient (patient 3) had severe bone lesions with multiple vertebral fractures. None of the patients had skin or lymph node involvement. Two patients (patients 1 and 2) died 12 and 9 months after diagnosis with acute nonlymphocytic leukemia and overt mastocytic leukemia, respectively, while the other two (patients 3 and 4) are alive 58 and 14 months after diagnosis. Treatment with hydroxyurea or cytosine arabinoside had not any beneficial effect in two patients, while a substantial amelioration of back pain had been obtained by local irradiation and recombinant human interferon-alpha-2b administration in one patient (patient 3). All patients had laboratory findings compatible with autoimmune cholangitis. We concluded that systemic mastocytosis is a rare cause of noncirrhotic portal hypertension often simulating autoimmune cholangitis and leading to the erroneous diagnosis of liver cirrhosis. Diagnosis is based on the presence of mast cells in Giemsa-stained liver histological sections, and it may be confirmed by immunohistochemical detection of tryptase in the cytoplasm of these abnormally proliferating cells.
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PMID:Systemic mastocytosis: a rare cause of noncirrhotic portal hypertension simulating autoimmune cholangitis--report of four cases. 944 86

Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.
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PMID:Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells. 1203 46

Mastocytoses are a heterogenous group of diseases characterized by proliferation and accumulation of mast cells in the skin and other organs. They are subdivided into cutaneous mastocytoses; systemic forms, which may appear with or without skin lesions; mast cell sarcomas and extracutaneous, localized, benign mastocytomas. Systemic mastocytoses apart from the skin mainly involve bone marrow, gastrointestinal tract, bones, lymph nodes, spleen and liver. Whereas indolent forms of systemic mastocytosis are mainly treated with antihistamines, glucocorticosteroids and PUVA therapy, the more aggressive forms, including mast cell leukemia, often require cytostatic chemotherapy. A 53-year old patient with beginning "smoldering systemic mastocytosis" failed to respond to high-dose systemic glucocorticosteroids and interferon-alpha. Treatment with cladribine led to an impressive improvement of skin lesions, a significant decrease in tryptase serum levels and stabilization of bone marrow infiltrates.
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PMID:["Smoldering systemic mastocytosis. "Successful therapy with cladribine]. 1524 20

Mast cell disease (MCD) is characterized by the abnormal growth and accumulation of neoplastic mast cells (MC) in one or more organs. The diagnosis of systemic MCD is most commonly established by a thorough histological and immunohistochemical examination of a bone marrow (BM) trephine specimen. In cases with pathognomonic perivascular and -trabecular aggregates of morphologically atypical MC and significant BM involvement, the diagnosis may be relatively straightforward. In contrast, when a sparse, loose pattern of MC infiltration predominates, or when MCs are obscured by an associated non-MC hematological neoplasm, a high index of suspicion and use of adjunctive tests, including special stains, such as tryptase and CD25, may be necessary to reach a diagnosis. The updated classification for MCD clarifies the clinical and pathological criteria for categorizing patients into relatively discrete subgroups. Some cases, however, such those with Fip1-like-1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA)(+) clonal eosinophilia associated with elevated serum tryptase levels, with features that overlap MCD and chronic eosinophilic leukemia, may not be easy to categorize on the basis of this classification. There is no standard therapy for MCD and treatment has to be tailored to the needs of the individual patient. MC-cytoreductive therapies, such as interferon-alpha and chemotherapy, are generally reserved for patients with progressive disease and organopathy. A subset of MCD patients with associated eosinophilia who carry the FIP1L1-PDGFRA oncogene will achieve complete clinical, histological, and molecular remissions with imatinib mesylate therapy, in contrast to those with c-kit D816V mutations. The BM pathology, consensus classification, and current therapies for MCD are further discussed in this article.
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PMID:Systemic mastocytosis: bone marrow pathology, classification, and current therapies. 1599 24

Hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), and mast cell disease (MCD) are all considered myeloproliferative neoplasms, and diagnosis in each instance requires bone marrow examination with cytogenetic and molecular studies. HES should be distinguished from both molecularly defined and otherwise uncategorized CEL. The genes that are mutated in molecularly defined CEL include those that encode for platelet-derived growth factor receptors A and B and for fibroblast growth factor receptor 1. Diagnosis of MCD is facilitated by tryptase immunostaining and immunophenotyping to detect abnormal CD25-positive mast cells. Mutation screening for KITD816V is also advised but is not essential for the diagnosis of MCD. Asymptomatic patients with HES and no evidence of organ damage do not necessarily require immediate therapy. The same is true for patients with indolent MCD. At present, effective cytoreductive drugs for HES include corticosteroids, interferon-alpha (IFN-alpha), and hydroxyurea, imatinib for platelet-derived growth factor receptor A or B-rearranged CEL imatinib, and for MCD IFN-alpha and cladribine. In addition, a number of new drugs are currently being tested for their safety and efficacy in all 3 disorders.
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PMID:Hypereosinophilic syndrome, chronic eosinophilic leukemia, and mast cell disease. 1803 76

We describe a case of systemic mastocytosis associated with myelodysplastic syndrome. The bone marrow showed multifocal clusters of mast cells and myeloid dysplasia. Sequencing of the KIT DNA revealed a point mutation at codon 816 including a substitution of valine for aspartic acid (D816V). The patient's tumor did not respond to imatinib; however, interferon-alpha reduced the bone marrow mast cells and serum total tryptase. The patient remains alive at one year after the diagnosis without disease progression.
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PMID:Successful treatment of KIT D816V-positive, imatinib-resistant systemic mastocytosis with interferon-alpha. 1991 99


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