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)

IkappaBgamma (IkappaBgamma) is a 70-kDa protein that is encoded by the C-terminal part of the NF-kappaB p105 gene and acts as an inhibitor of the transcription factor NF-kappaB. Until now, IkappaBgamma expression has only been described in cell-culture models of B-lymphocytes and enterocytes but not in tissues. In a model of radiation-induced pulmonary damage, we found that mast cells accumulating after irradiation are the only cells in the rat lung that are positive for IkappaBgamma. The mast cells were characterised by their metachromatic staining with toluidine blue and by double immunofluorescence labelling with mast-cell tryptase. Western blotting revealed that the lung mast cells expressed the 70-kDa form of IkappaBgamma cytoplasmatically and that no alternative splicing variants were expressed. In addition, we studied 11 cases of systemic mastocytosis, as well as 5 cases of mast-cell hyperplasia. In all cases, the mast cells stained strongly with IkappaBgamma. Rat peritoneal mast cells also contained high levels of IkappaBgamma. Since NF-kappaB is an important regulator of mast-cell functions, IkappaBgamma is likely to play a central role in the maintenance of the mast-cell phenotype and possibly in the modification of mast-cell-dependent immune responses.
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PMID:IkappaBgamma is expressed in mast cells. 1537 59

In patients with mastocytosis, gastrointestinal symptoms are a frequent phenomenon. However, there are only limited data about the quantity and distribution pattern of mast cells in the gastrointestinal mucosa. We stained gastroduodenal biopsy specimens from 27 patients with mastocytosis and 48 control subjects for mast cell tryptase, CD117, and CD25. The numbers of mucosal mast cells per high-power field showed wide variation in all groups and were decreased markedly in biopsy specimens of corpus and duodenum and statistically significantly decreased in antrum biopsy specimens from patients with systemic mastocytosis compared with patients with pure urticaria pigmentosa and with control subjects. Staining for tryptase showed highly significant correlation with staining for CD117. All mast cells were negative for CD25, which is expressed characteristically by neoplastic mast cells. Causes of the decrease of mucosal mast cells remain enigmatic, but our results show that gastrointestinal symptoms of patients with mastocytosis are most likely mediator-related and not due to an increase of local mast cells.
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PMID:Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? 1548 54

Mastocytosis comprises a heterogeneous group of disorders characterized by proliferation and accumulation of mast cells in 1 or more organ systems. Mast cell leukemia (MCL) is an extremely rare subtype of mastocytosis in which a leukemic spread of mast cells and a rapid progression of disease is seen. In typical cases, mast cells are found in the peripheral blood. However, an aleukemic variant of MCL (formerly termed malignant mastocytosis) has also been described. We here report a case of aleukemic MCL with abnormal immunophenotype of mast cells and the classical c-kit point mutation Asp-816-Val (=D816V). The 75-year-old male patient had a short history of weight loss and lymphadenopathy. There were no urticaria pigmentosa-like skin lesions. The bone marrow was diffusely infiltrated with atypical mast cells that comprised more than 80% of all nucleated cells on a bone marrow smears. As assessed by immunohistochemistry, neoplastic mast cells expressed tryptase, chymase, CD2, CD25, CD68, and the KIT protein (CD117). Mutation analysis revealed the c-kit mutation D816V. Since circulating mast cells could not be detected in the peripheral blood, the diagnosis of aleukemic MCL was established in accordance to the updated WHO consensus classification. This case further supports the notion that the pathogenesis (c-kit mutation D816V) in MCL is closely related to that found in indolent mast cell disorders. However, additional (but yet unknown) molecular (genetic) defects have to be considered to explain the extremely heterogenous clinical course in these patients.
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PMID:Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation D816V. 1551 20

With the occurrence of unclear consciousness conditions primarily internal or neurological causes are considered. Of a systemic mastocytosis one thinks only rarely, which can accompany without or with slight clinically visible skin changes. In the following we report on a patient who has repeated unclear shock conditions and required resuscitation several times without a recognizable cause, with whom a systemic mastocytosis could be proven. Clinically very discrete lesions of mastocytosis were recognizable from the skin. Only an increased tryptase level referred to being present an occult systemic mastocytosis. The diagnostics, potential triggers and therapy of this disease are to be discussed on the basis the available case.
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PMID:[Anaphylactoid reaction in occult systemic mastocytosis. A rare dermatologic emergency ]. 1561 82

We describe the case of a 56-year-old man with rapidly progressive osteoporosis culminating in pathologic fractures of multiple lumbar vertebrae. With the exception of discrete brown-reddish cutaneous lesions, low back pain was the only prominent symptom. Laboratory evaluations excluded metabolic or endocrinological abnormalities. Serum tryptase was highly increased, as was urinary excretion of histamine. Iliac crest biopsy demonstrated mastocytosis, which was confirmed by skin biopsy and which was consistent with teleangiectasia macularis eruptiva perstans, a rare form of cutaneous mastocytosis. In cases of unusually marked osteoporosis, especially in men, mastocytosis should be considered in the differential diagnosis.
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PMID:A case of systemic mastocytosis associated with severe osteoporosis and pathologic fractures. 1566 93

The clinical spectrum of mast cell disease ranges from relatively innocuous and histologically subtle urticarial skin lesions to an aggressive and fatal leukemic form of mast cell proliferation. Not surprisingly, mast cell infiltrates may show significant microscopic heterogeneity, particularly in the bone marrow, the most common site of involvement in systemic mastocytosis (SM). Herein, 3 cases are presented to illustrate the clinical and morphologic heterogeneity of mast cell disease: the first patient, with long standing urticaria pigmentosa, developed anemia and thrombocytopenia; the second patient presented with a pathologic fracture; and the third patient was suspected to have refractory anemia. Upon bone marrow examination, all 3 patients showed mast cell infiltration with distinct morphologic features and all met the WHO criteria for aggressive systemic mastocytosis. Histochemical methods continue to play a role in the identification of mast cells, with some limitations depending on the degree of differentiation of the mast cells and tissue processing methods. Immunohistochemistry has contributed to the identification of mast cells. Coexpression of CD117 and CD25, as well as expression of the more specific immunohistochemical marker tryptase, is seen in systemic SM. The latter may also be employed as a serum marker in the diagnosis and follow-up of patients with SM. The mast cells, in the majority adults with SM, have somatic point mutations of KIT.
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PMID:The faces of mast cell disease: bone marrow infiltrates in 3 patients with systemic mastocytosis. 1580 14

Mastocytosis is often associated with organ involvement and hematological disorders. Patients may also exhibit elevated levels of plasma IL-6. To gain insight into the relevance of this observation, we correlated plasma levels of IL-6 and soluble IL-6 receptor (sIL-6R) with multiple disease parameters in 29 patients with mastocytosis. Mean plasma IL-6 levels were elevated in patients compared to healthy controls (P < 0.0001). Disease category significantly correlated with plasma IL-6 levels, as did severity of bone marrow pathology, organomegaly, and extent of skin involvement. In plasma, there was a positive correlation of IL-6 to total tryptase, alkaline phosphatase, IgM, white blood cell count, prothrombin time, partial thromboplastin time, and neutrophil numbers. There was an inverse correlation to hemoglobin. sIL-6R levels were not elevated. These observations demonstrate that IL-6 is a useful surrogate marker of severity of hematologic disease and suggest that IL-6 contributes to pathology.
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PMID:IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis. 1588 46

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

Uptake of monoamines into secretory granules is mediated by the vesicular monoamine transporters VMAT1 and VMAT2. In this study, we analyzed their expression in inflammatory and hematopoietic cells and in patients suffering from systemic mastocytosis (SM) and chronic myelogenous leukemia (CML). Normal human and monkey tissue specimens and tissues from patients suffering from SM and CML were analyzed by means of immunohistochemistry, radioactive in situ hybridization, real time RT-PCR, double fluorescence confocal laser scanning microscopy, and immunoelectron microscopy. In normal tissue specimens, VMAT2, but not VMAT1, was expressed in mast cells, megakaryocytes, thrombocytes, basophil granulocytes, and cutaneous Langerhans cells. Further hematopoietic and lymphoid cells showed no expression of VMATs. VMAT2 was expressed in all types of SM, as indicated by coexpression with the mast cell marker tryptase. In CML, VMAT2 expression was retained in neoplastic megakaryocytes and basophil granulocytes. In conclusion, the identification of VMAT2 in mast cells, megakaryocytes, thrombocytes, basophil granulocytes, and cutaneous Langerhans cells provides evidence that these cells possess molecular mechanisms for monoamine storage and handling. VMAT2 identifies normal and neoplastic mast cells, megakaryocytes, and basophil granulocytes and may therefore become a valuable tool for the diagnosis of mastocytosis and malignant systemic diseases involving megakaryocytes and basophil granulocytes.
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PMID:Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis. 1611 33

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.
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PMID:Diagnosis of Hymenoptera venom allergy. 1619 64


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