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

---

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

Hymenoptera venom allergy (HVA) is a typical IgE-dependent allergy. Its diagnosis includes confirmation of the presence of specific IgE antibodies to venom allergens (vsIgE), and its treatment is based on developing of immunotolerance (venom immunotherapy, VIT). In most cases of sting anaphylaxis, vsIgE can be found, in some, however, the antibodies are undetectable, in spite of systemic reaction to venom, which may be due to low specificity of diagnostic methods. Diagnostic methods might be improved by the use of recombinant allergens which, being "uncontaminated" by other venom constituents, allow for a precise setup of "individual allergogram." A diagnostic novelty is the tryptase serum level assay that is capable of confirming ex-post anaphylaxis and coincidence of mastocytosis. The diagnostic procedures applied in venom allergy make possible only to prove the existence of allergy while it is impossible to estimate, on their basis, the risk of development and intensification of future reactions. New diagnostic concept that could supplement the imperfect diagnostic armamentarium is still lacking. Clinical practice has proven that VIT is a very effective method of protection of patients with IgE-dependent wasp-sting anaphylaxis, but both the effectiveness and safety of VIT in patients allergic to bee venom are not optimal. The future of VIT is the use of modified, recombinant allergens or their peptide fragments, but clinical data on their effectiveness are unavailable as yet. The safety of VIT can be increased by means of introducing premedication with antihistamines.
...
PMID:[New variants of diagnostic procedures and therapeutic methods in insect venom allergy]. 1452 9

SERPINB6 (PI6) is a member of the intracellular serine protease inhibitors (serpins). Previous studies showed that SERPINB6 is localized mainly in the cytoplasm of endothelial cells, some epithelial cells, monocytes, and neutrophils. In these cells SERPINB6 is thought to prevent cellular damage by scavenging leaking lysosomal proteases. We show here, using novel, well-defined monoclonal antibodies, that SERPINB6 is abundantly expressed by mast cells in all organs and by the human mast cell line HMC-1. Gel filtration experiments revealed that the latter cells contain a high-molecular-weight form of SERPINB6, which consists of sodium dodecyl sulfate (SDS)-stable complexes of this inhibitor with monomeric beta-tryptase. Expression of SERPINB6 by mast cells was compared with those of tryptase and CD117 (c-kit) in biopsies from patients with different forms of mast cell disease. In all cases the lesional mast cells expressed SERPINB6, and, in diffuse cutaneous mastocytosis and mastocytoma, SERPINB6 was expressed by a substantially higher number of mast cells when compared with tryptase. In conclusion, SERPINB6 is abundantly expressed by normal mast cells and by mast cells in mastocytoma lesions. We suggest that in mast cells, SERPINB6 serves to regulate the activity of endogenous beta-tryptase in the cytoplasm.
...
PMID:Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with beta-tryptase monomers. 1467 Sep 19

Approximately 20% of patients with systemic mastocytosis (SM) have an associated haematological, clonal, non-mast cell lineage disease, and most exhibit an associated myelogenous neoplasm. This report describes a 48 year old man with acute myeloid leukaemia (AML) and a type t(8;21) cytogenetic abnormality. Associated bone marrow mastocytosis (a defined subtype of SM) was only detected after successful polychemotherapy in the state of bone marrow aplasia, and persisted after complete remission of AML. The diagnosis of mastocytosis was based on the demonstration of a multifocal dense mastocytic infiltrate. The atypical mast cells showed prominent spindling and an aberrant immunophenotype, with coexpression of tryptase, chymase, KIT, and CD25-which is expressed only on neoplastic (not normal) mast cells. In addition, the transforming somatic mutation D816V of the c-kit gene was detected. Re-examination of the pretherapeutic (initial) bone marrow revealed a slight diffuse increase in partially spindle shaped mast cells also exhibiting an abnormal immunophenotype, with CD25 expression, although compact mastocytic infiltrates were not detected. Because the D816V mutation was detected in the initial bone marrow specimen, strict application of three minor diagnostic criteria (spindling, CD25, D816V) enabled a diagnosis of SM-AML to be confirmed retrospectively in the initial bone marrow tissue.
...
PMID:Acute myeloid leukaemia with t(8;21) associated with "occult" mastocytosis. Report of an unusual case and review of the literature. 1499 Jun 11

Systemic anaphylaxis arises when mast cells, possibly along with other cell types, are provoked to secrete mediators that evoke a systemic response. Mast cells in perivascular, respiratory, gastrointestinal and cutaneous tissues are likely involved, regardless of whether IgE or non-IgE-dependent pathways are invoked. Alpha/beta tryptases are selectively and abundantly produced by mast cells. Tryptase levels in the circulation provide a precise indicator of mast cell involvement. Mature beta tryptase is stored in secretory granules and is released when the cells are activated to degranulate, as occurs in anaphylaxis. Alpha/beta pro/pro' tryptases are spontaneously secreted by mast cells. Consequently, mature tryptase levels in serum (normally 1 ng/ml) are elevated in systemic anaphylaxis. Total tryptase levels (mature plus precursor forms), normally 1-15 ng/ml in baseline serum samples, are elevated in patients with systemic mastocytosis (> 20 ng/ml), a disease that also predisposes one to anaphylactic reactions. The assessment of basophils in systemic anaphylactic reactions has been problematic, because an assay for a specific releasable marker from this cell type has not been developed. Nevertheless, in cases of anaphylaxis in which elevations of histamine, but not tryptase, have been detected, it is enticing to speculate that basophil-dependent anaphylaxis may have occurred.
...
PMID:Effector cells of anaphylaxis: mast cells and basophils. 1502 92

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.
...
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.
...
PMID:Mastocytosis: classification, diagnosis, and clinical presentation. 1505 60

Monoamine storage in secretory granules is mediated by the vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2). The aim of our study was to identify monoamine-handling normal and neoplastic inflammatory cells in the skin by their expression of VMAT1 and VMAT2. Normal skin from various parts of the body, as well as 21 cases of cutaneous mastocytosis and 10 cases of cutaneous Langerhans cell histiocytosis were analyzed by immunohistochemistry, radioactive in situ hybridization, and double-fluorescence confocal microscopy. VMAT2-positive cells in the subepidermal layer were identified as mast cells by their expression of tryptase. Neoplastic mast cells in all cases of cutaneous mastocytosis retained their VMAT2 positivity. The intraepidermal VMAT2-expressing cells were identified as Langerhans cells by their CD1a positivity. VMAT2 was absent from Langerhans cell histiocytosis. VMAT2 is an excellent marker for normal and neoplastic mast cells. The expression of VMAT2 demonstrates the capacity of mast cells for monoamine storage and handling. The presence of VMAT2 in epidermal Langerhans cells revealed a previously unrecognized monoamine-handling phenotype of these cells and indicates possible involvement of amine storage and release associated with antigen presentation. Absence of VMAT2 in neoplastic Langerhans cells indicates a loss of monoamine handling capacity of these cells during tumorigenesis.
...
PMID:The vesicular monoamine transporter 2 (VMAT2) is expressed by normal and tumor cutaneous mast cells and Langerhans cells of the skin but is absent from Langerhans cell histiocytosis. 1515 Feb 86

An association between mastocytosis and monoclonal gammopathy is a relatively rare but well recognized clinical finding. In the majority of cases, however, overt myeloma or lymphoma is not detectable morphologically. Here we describe the case of a 51 year-old male patient first presenting with paresis of the right facial nerve and the serological finding of IgM kappa paraproteinemia. The patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa-type skin lesions. Histological examination of a trephine biopsy specimen revealed the unusual coexistence of plasma cell myeloma and mastocytosis. Immunohistochemically, plasma cells were found to exhibit a monotypic staining for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic nature. Mast cells showed prominent spindling and formed dense multifocal infiltrates, thus enabling the diagnosis of bone marrow mastocytosis. Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117). In addition, aberrant expression of CD25 on mast cells was detected, confirming the coexistence of a neoplastic mast cell-proliferative disorder. According to the WHO proposal for classification of hematopoietic malignancies, this unique case, showing the association of two very rare haematologic neoplasms, can therefore best be referred to as bone marrow mastocytosis associated with IgM kappa plasma cell myeloma (SM-AHNMD).
...
PMID:Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma. 1516 Sep 59

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.
...
PMID:["Smoldering systemic mastocytosis. "Successful therapy with cladribine]. 1524 20

The diagnosis of systemic mastocytosis (SM) is based primarily on the histologic and immunohistochemical evaluation of a bone marrow trephine biopsy specimen. Although mast cell (MC) specific antigens like tryptase and chymase are detectable in routinely processed tissue, no immunohistochemical markers that can be used to discriminate between normal and neoplastic MCs are yet available. We have investigated the diagnostic value of an antibody against CD25 for the immunohistochemical detection of MCs in bone marrow sections in 73 patients with SM and 75 control cases (reactive marrow, n = 54; myelogenous neoplasms, n = 21) and correlated the results with the presence of c-kit mutations. While MCs in almost all patients with SM (72 of 73) expressed CD25, none of the control samples contained CD25-positive MCs. Irrespective of the SM subtype, most of neoplastic MCs expressed CD25. In 3 patients with advanced MC disease, pure populations of neoplastic MCs were obtained and found to express CD25 mRNA by RT-PCR analysis. In addition, all patients with CD25-positive MCs contained c-kit mutations, while all control cases exhibited wild type c-kit. CD25 therefore appears to be a reliable immunohistochemical marker for the discrimination of neoplastic from normal/reactive MCs, with potential as a diagnostic tool in SM.
...
PMID:CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens. 1537 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---