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)

Multiple early untreated lesions of angiomatosis retinae in the peripheral retina and optic disk were discovered after death in both eyes of a patient with von Hippel-Lindau disease. Each of the four peripheral angiomas was studied by a different technique: routine light microscopy of serial histologic sections, electron microscopy, flat mount and trypsin digestion, and frozen section with special stains for lipid. The large capillaries comprising the core of each angioma displayed normal endothelium, basement membrane, and pericytes. Thus, capillary hemangioma of the retina is a more correct histopathologic designation for the von Hippel angioma than terms such as hemangioblastoma or hemangioendothelioma. Interstitial cells separating the vascular channels of the angioma were identified as astrocytes that contain large lipid-filled cacuoles. Serial histologic sections demonstrated that both retinal and choroidal vessels communicate with vascular channels of the juxtapapillary capillary hemangiomas.
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PMID:Light and electron microscopic study of early lesions in angiomatosis retinae. 98 18

Mast cells play an essential role during development of inflammation after chemical and immunological insults and have been implicated in tissue fibrosis and angiogenesis. The exact contribution of mast cells to these conditions is largely unknown. In this study, we found that a potent angiogenic and mitogenic polypeptide, basic fibroblast growth factor (bFGF), is localized to the majority of mast cells from normal skin and lung and in tissue samples characterized by fibrosis, hyperplasia, and neovascularization. Using specific antibodies to mast cell tryptase, tissue macrophage, and bFGF, we demonstrate that cytoplasmic bFGF immunoreactivity is localized to 96.8 +/- 9.6% of tryptase-positive cells in human fibrotic lung tissue (n = 10), 82.3 +/- 6.9% of tryptase-positive cells in rheumatoid synovia (n = 6), and 93.1 +/- 4.8% of tryptase-positive cells in skin hemangioma (n = 5). Moreover, these tryptase-positive cells comprise a major portion (86 to 97%) of nonvascular cells exhibiting cytoplasmic bFGF staining in these tissues. In contrast, macrophage-like cells contribute less than 10% of the bFGF-positive cells in the same samples. The specificity of the immunostaining results was supported by the finding that cultured human mast cells (HMC-1) express both bFGF mRNA and protein. Our data indicate that mast cells, a primary source of heparin, also serve as a significant source of a heparin-binding growth factor, bFGF, in these disease processes. These observations suggest that mast cells may contribute to these pathological conditions by releasing this polypeptide.
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PMID:Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. 754 72

The "densities" of mast cells (MCs) in six kinds of vascular proliferation, pyogenic granuloma, portwine stain, cavernous hemangioma, cherry angioma, Kaposi's sarcoma, and malignant hemangioendothelioma (MHE), measured per mm2 were studied using respective specimens prepared with tryptase stain and a personal computer. The average densities of MCs in pyogenic granuloma and MHE were 103.5 +/- 25.2/mm2 (n = 10) and 106.3 +/- 40.2/mm2 (n = 10) [mean +/- standard deviation (SD)]; that in normal skin was 6.85 +/- 4.9/mm2 (n = 20) (mean +/- SD). is a significant difference [t-test (p < 0.0001) and Wilcoxon-test (p < 0.01)]. The results in portwine stain (n = 4), cavernous hemangioma (n = 9), cherry angioma (n = 4), and Kaposi's sarcoma (n = 4) were 68.6 +/- 28.9/mm2, 105.7 +/- 56.9/mm2, 85.3 +/- 45.6/mm2, 82.2 +/- 28.4/mm2 (mean +/- SD), respectively, all of which were greater than that in normal skin by a simple comparison. The results of immunofluorescence microscopy were positive with basic fibroblast growth factor staining in the tissues of pyogenic granuloma, Kaposi's sarcoma and MHE. These facts may morphologically indicate a role of MCs in the angiogenesis of these vascular tumors.
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PMID:Mast cell "densities" in vascular proliferations: a preliminary study of pyogenic granuloma, portwine stain, cavernous hemangioma, cherry angioma, Kaposi's sarcoma, and malignant hemangioendothelioma. 1053 52

Polydocanol has a wide range of medical applications, especially in sclerotherapy of many diseases such as gastrointestinal antiplastia, oesophageal haemangioma etc. It is of interest to study the mode of binding of this medically important detergent and its subsequent action on proteins. Here, three crystal structures of serine protease trypsin are reported in the presence of varying concentrations of polydocanol in order to elucidate its mode of binding and interactions with proteins. Polydocanol binds to the protein with its hydrophilic head rather than the hydrophobic tail as is the case with other detergents such as SDS and MEGA-8. This hydrophilic binding mode results in the binding sites of polydocanol being distributed on the surface of the enzyme. There are at least 11 binding sites for polydocanol in trypsin. Polydocanol forms part of the large-scale water networks which connect distant regions of the enzyme, thereby stabilizing it. The hydrophilic binding of polydocanol also results in cross-linked pairs of trypsin molecules.
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PMID:Structures of porcine beta-trypsin-detergent complexes: the stabilization of proteins through hydrophilic binding of polydocanol. 1167 13

Hemangioma is a primary tumor of the microvasculature in which angiogenesis is initially excessive, followed by spontaneous regression of the newly formed vessels, with the cellular parenchyma gradually being replaced with fibrofatty tissue. Mast cells, which are highly heterogenous in terms of their morphology, function, and metabolic products, have been implicated in the pathophysiology of hemangioma. Csaba stain shows that mast cells are predominantly of the biogenic amine phenotype throughout the development of hemangioma. The predominance of this phenotype remains unaltered following successful steroid therapy, although their number increases fourfold. Mast cells, all of which stain positive for tryptase, and those that stain positive for chymase as well, have been identified in hemangioma biopsy specimens throughout the three developmental phases. The total number of mast cells is highest during the involuting phase, less in the involuted phase, and least in the proliferative phase. The proportion of mast cells that contain both tryptase and chymase decreases from the proliferative through involuting to the involuted phase. This decreasing proportion of mast cells that contain both tryptase and chymase with ongoing involution parallels that of progressive deposition of the extracellular matrix as indicated by increasing fibrosis and fatty deposition. The short-chain type VIII collagen, thought to play a key role in angiogenesis, has been detected throughout the developmental phases of hemangioma. It has been postulated that this collagen, which is produced early in new vessel development, provides a substratum to facilitate the migration of endothelial cells. It may also facilitate the deposition of other extracellular constituents and influence cell movement and the maintenance of cell phenotypes. The intracellular localization of type VIII collagen in mast cells only in the early proliferative phase suggests that there is an active synthesis by mast cells during this phase. The increasing extracellular localization during hemangioma development may be caused by an increased secretion of protein from intracellular stores. The increased number of mast cells during the involuting phase indicates that these cells may play a role in the regression of hemangioma. This is in contrast to the large body of evidence showing the proangiogenic role of mast cells. The proportion of proliferating mast cells decreases, whereas the proportion of mast cells positive for clusterin/apolipoprotein J increases with ongoing involution of hemangioma. Clusterin/apolipoprotein J expression has been considered as a prominent marker of apoptotic cell loss. The presence of clusterin/apolipoprotein J granules both in the adjacent endothelial cells and in capillary lumens suggests that mast cells may be secreting this apoptotic modulator to promote the regression of hemangioma. Certain effectors produced by mast cells may participate in the development of hemangioma. It has been proposed that one of the functions of mast cells is to release factors leading to the regression of hemangioma. The evidence suggests that although mast cells may have a function in the endothelial proliferation in hemangioma, they also play a crucial role in the regression of this tumor. However, the roles of mast cells in the life cycle of hemangioma are likely to be complex and may involve stimulators of angiogenesis in the proliferative phase but inhibitors in later phases.
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PMID:Mast cells and hemangioma. 1510 98

We report the morphological characteristics of 30 cases of sclerosing hemangioma (SH) of the lung and explore the histological origin of the major cells in these tumors. In addition to routine light and electron microscopy, immunohistochemistry was performed by using 12 monoclonal primary and 5 polyclonal primary antibodies. These included surfactant protein B (SP-B), thyroid transcription factor-1 (TTF-1), mast cell trypsin, CD68, epithelial antigen markers (high molecular weight cytokeratin, low molecular weight cytokeratin [CK-L], epithelial membrane antigen [EMA], cancer embryonic antigen), mesothelial antigen, neuroendocrine markers (neuron-specific enolase [NSE], chromogranin A, synaptophysin, calcitonin, adrenocorticotropic hormone, human growth hormone [hHG]), vimentin, and CD34. Surface cuboidal cells have short microvilli and have lamellar bodies in their cytoplasm. They can sometimes merge into multinuclear giant cells. Immunohistochemical results showed that these cells are strongly positive for SP-B, TTF-1, CK-L, EMA, and cancer embryonic antigen, whereas polygonal cells, previously also described as round or pale cells, were strongly positive for vimentin and TTF-1, and positive or weakly positive for 2 to 3 kinds of neuroendocrine markers. Sparse neuroendocrine granules and abundant microfilaments were observed in their cytoplasm. Some cell clusters in the solid regions were positive for SP-B and EMA. Mast cells existed sparsely in almost every field. Both cuboidal and polygonal cells were negative to CD34 and mesothelial antigen staining. We conclude that cuboidal cells of SH originate from reactive proliferating type II pneumocytes, which can fuse into multinuclear giant cells. Polygonal cells, as true tumor cells, likely originate from multipotential primitive respiratory epithelium and possess the capability for multipotential differentiation. The antibodies of SP-B, TTF-1, vimentin, and CK-L are very helpful to diagnosis and differential diagnosis of SH.
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PMID:Immunohistochemical and ultrastructural markers suggest different origins for cuboidal and polygonal cells in pulmonary sclerosing hemangioma. 1511 33

Propranolol is increasingly used to treat problematic infantile haemangioma (IH), although its molecular mechanisms remain unclear. A key feature of propranolol therapy is the decreased deposition of fibrofatty residuum compared with spontaneously involuting IH. This study investigated the molecular consequences of propranolol treatment for IH in vivo.Immunohistochemical and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining was performed on five age matched patients with proliferative IH. Two patients (A and B) were undergoing propranolol treatment at the time of surgical resection.Propranolol treatment increased apoptosis, and induced mast cells to degranulate and secrete tryptase into the interstitium. The microvessels of patient A were immature [weak von Willibrand Factor (vWF), and strong osteoprotegerin (OPG) staining], comparable to untreated proliferative IH, while those of patient B were mature (strong vWF staining, and no OPG staining). The perivascular CD90 mesenchymal stem cell population was preserved in both propranolol treated patients.Using rarely obtained biopsies from IH patients treated with propranolol, we show increased apoptosis by propranolol for the first time in vivo. We also suggest that mast cells, through secreted proteases, may contribute to the decreased fibrofatty residuum seen with propranolol treatment.
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PMID:Increased apoptosis and secretion of tryptase by mast cells in infantile haemangioma treated with propranolol. 2515 19