Disease relevance of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events [1].
• One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter [1].
• In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20) [1].
• Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2 [2].
• Mast cells infiltrate hyperplasias, dysplasias, and invasive fronts of carcinomas, but not the core of solid tumors, where they degranulate in close apposition to capillaries and epithelial basement membranes, releasing mast-cell-specific serine proteases MCP-4 (chymase) and MCP-6 (tryptase) [3].

Psychiatry related information on N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau [4].

High impact information on N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis [1].
• Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation [2].
• Serine proteinases such as thrombin, mast cell tryptase, trypsin, or cathepsin G, for example, are highly active mediators with diverse biological activities [5].
• After coculture with HUVECs, most MCs were of the tryptase and chymase double-positive phenotype (MC(TC)) [6].
• Protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, modulates smooth muscle tone and exocrine secretion in the salivary glands and pancreas [7].

Chemical compound and disease context of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1 [8].
• Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness [9].
• We recently described a subset of patients with a myeloproliferative variant of hypereosinophilic syndrome (MHES) characterized by elevated serum tryptase levels, increased atypical mast cells in the bone marrow, tissue fibrosis, and the presence of the fusion tyrosine kinase, FIP1L1-PDGFRalpha, which is a therapeutic target of imatinib mesylate [10].
• The increases of C3 and CCL2 synthesis by C3a and C3 activation by skin mast cell tryptase delineates a novel amplification loop of complement activation and inflammatory responses that may influence the pathogenesis of allergic/inflammatory skin diseases [11].
• Luminal trypsin and tryptase are elevated in the colon of inflammatory bowel disease patients [12].

Biological context of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• Based on nucleic acid sequence, human tryptase consists of a 244-amino acid catalytic portion of 27,423 D with two putative N-linked carbohydrate binding sites and a 30-amino acid leader sequence of 3,048 D [13].
• Nanomolar concentrations of dog tryptase strongly stimulate thymidine incorporation in Chinese hamster lung and Rat-1 fibroblasts and increase cell density in both subconfluent and confluent cultures of these cell lines [14].
• Inhibitors of catalytic activity decrease the mitogenic capacity of tryptase, suggesting, though not proving, the participation of the catalytic site in cell activation by tryptase [14].
• The catalytic portion of human tryptase had an 84% amino acid sequence similarity with that of dog tryptase; their leader sequences had a 67% similarity [13].
• Tryptase levels then declined under apparent first order kinetics with a t1/2 of approximately 2h [15].

Anatomical context of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation [1].
• Mast cell tryptase is a mitogen for cultured fibroblasts [14].
• Mast cell tryptase causes airway smooth muscle hyperresponsiveness in dogs [16].
• The enhanced contractile response was reversed completely by H1-receptor antagonists and was prevented by an inhibitor of tryptase (a major protease released with histamine from secretory granules of mast cells) [16].
• Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2 [17].

Associations of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester with other chemical compounds

• Second, the NH2-terminal activation dipeptide on beta-pro'tryptase is removed by dipeptidyl peptidase I at acid pH in the absence of heparin to yield an inactive monomeric form of tryptase [18].
• Most imatinib-responsive HES patients show an increased number of bone marrow mast cells and elevated serum tryptase; mast cells, lymphocytes and neutrophils express the novel kinase [19].
• DNA synthesis in tryptase+ mast cells at days 21 and 28 of culture with rhuSCF was demonstrated by incorporation of bromodeoxyuridine [20].
• Mast cells were identified by immunohistochemistry using a specific monoclonal antibody (AA1) raised against mast cell tryptase after an initial study showed this to be more sensitive for the detection of mast cells than the conventional histochemical stain, toluidine blue [21].
• Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase [22].

Gene context of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• One mast-cell product, the serine protease tryptase, is known to activate protease-activated receptor 2 (PAR2) and cause proliferation of fibroblasts [23].
• We found that recombinant tryptase, human mast-cell (HMC-1) supernatant, which contains tryptase, and the PAR2-activating peptide SLIGKV exert fibroproliferative actions in human fibroblasts [23].
• Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARgamma : Possible relevance to human fibrotic disorders [23].
• Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture [8].
• Because MMCP-5 is a chymase and MMCP-6 a tryptase, there was a possibility that the difference in regulation mechanisms was associated with their different characteristics as proteases [24].

Analytical, diagnostic and therapeutic context of N-[(1S)-1-[[(1S)-1-[[(1S)-4-guanidino-1-[(5-methyl-2-oxo-chromen-7-yl)carbamoyl]butyl]carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-phenyl-ethyl]carbamic acid tert-butyl ester

• 5. Gel filtration of released material separated the activity from tryptase and demonstrated an approximate molecular weight of 30-35,000 [25].
• Tryptase was isolated from human lung tissue by ion-exchange and affinity chromatography [26].
• Intravascular tryptase-positive, FITC-avidin-positive, CD11b-negative mast cell precursors were noted in the area of healing and in the cardiac lymph after 48 to 72 hours of reperfusion [27].
• Metachromatic cells in cytospins were identified as mast cells primarily on the basis of tryptase expression, and as MCT or MCTC by immunohistochemistry using monoclonal antibodies against tryptase and chymase, whereas basophils were metachromatic, polymorphonuclear, and lacked these proteases [20].
• In this study, serum total tryptase levels were determined in 150 patients with acute leukemias (de novo acute myeloid leukemia [AML], n = 108; secondary AML, n = 25; acute lymphoid leukemia [ALL], n = 17) by fluoroenzyme immunoassay [28].

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