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:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antineutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produce a characteristic cytoplasmic staining pattern of neutrophils (c-ANCA) and are directed against proteinase 3 (Pr3), a serine protease from the azurophilic granules. c-ANCA, more or less equivalent to anti-Pr3, occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement, and in some 40% to 50% of patients with vasculitic overlap syndromes suggestive of WG such as microscopic polyarteritis. The presence of c-ANCA is highly specific for those diseases (greater than 98%). Changes of levels of c-ANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (p-ANCA) occur in a wide range of diseases. They are directed against different cytoplasmic constituents of neutrophils. Among those, antibodies to myeloperoxidase are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa with visceral involvement, and vasculitic overlap syndromes. Their specificity for this group of necrotizing vasculitides is high (94% to 99%), although they may occur in patients with hydralazine-induced glomerulonephritis, anti-glomerular basement membrane disease, and possibly in some patients with idiopathic systemic lupus erythematosus. Antibodies to leukocyte elastase are incidentally found in patients with vasculitic disorders, whereas lactoferrin antibodies are detected in patients with primary sclerosing cholangitis with or without ulcerative colitis and in rheumatoid arthritis. Their diagnostic significance awaits further studies. p-ANCA of undefined specificity may distinguish ulcerative colitis (sensitivity of 75%) from Crohn's disease (sensitivity of 20%). p-ANCA also occur in autoimmune liver diseases: in 75% of patients with chronic active hepatitis, in 60% to 85% of those with primary sclerosing cholangitis, and in about 30% of patients with primary biliary cirrhosis. Finally, p-ANCA are detected in chronic arthritides and in some 5% of healthy controls. Assessment of their diagnostic value has to await further characterization of the antigens involved, allowing the development of antigen-specific assays.
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PMID:Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders. 782 11

To assess leukocyte activation during cardiopulmonary bypass, we measured white blood cell and neutrophil counts and lysosomal enzyme release, especially myeloperoxidase and elastase, throughout the operation and for 5 days postoperatively. A newly developed double antibody radioimmunoassay of myeloperoxidase and an enzyme-linked immunosorbent assay for detection of the polymorphonuclear elastase-alpha 1-proteinase inhibitor complex were used to determine their plasma levels in 15 patients undergoing elective aorta-coronary bypass grafting. Preoperatively white blood cell counts and plasmatic levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor were normal. Because no correlation has yet been established between levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor, the aim of this prospective study was to evaluate the use of these enzyme levels as markers for leukocyte activation in vivo. We addressed the clinical situation of cardiopulmonary bypass because it offered the possibility of monitoring the comparative evolution of blood levels of these enzymes in parallel to white blood cell counts through well-defined steps corresponding to known events. We document the advantages of myeloperoxidase blood levels over elastase measurement as reflecting more rapidly the in vivo activation of leukocytes. The time course kinetics of these three measurements were not parallel. White blood cell counts remained stable at the beginning of bypass, whereas myeloperoxidase levels increased sharply and continuously as soon as bypass was instituted until the end of bypass. Elastase levels also increased, but later than myeloperoxidase, beginning when the patients was rewarmed. High elastase plasma levels persisted later than myeloperoxidase after bypass, in parallel with white blood cell counts. It thus clearly appears that changes in myeloperoxidase levels more rapidly reflect the activation state of leukocytes induced by cardiopulmonary bypass and surgery, whereas peak levels of elastase were delayed and parallel to white blood cell counts. From this model, in which the evolution of leukocyte numbers could be followed in relation with known steps of stimulation, it appears that myeloperoxidase is a sensitive marker for monitoring in vivo activation of white blood cells.
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PMID:Myeloperoxidase and elastase as markers of leukocyte activation during cardiopulmonary bypass in humans. 186 4

The results presented during the Third International ANCA Workshop, Washington, DC, 1990, allowed a better definition of the antigenic specificity of the antineutrophil cytoplasmic autoantibodies (ANCA). The large predominance of two major antigen specificities for proteinase 3 (PR3) and myeloperoxidase (MPO), in the group of vasculitic patients, was confirmed. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation and thus are able to interact with ANCA after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, the agreement was reached that PR3 was identical to AGP7, p29, and myeloblastin, described independently and involved in the control of growth and differentiation of leukemic cells. In addition to the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been previously identified (human leukocyte elastase [HLE], lactoferrin). It was established during the Third Workshop that these rare ANCA specificities, occurring in a limited number of patients, include a cationic antimicrobial protein (CAP57) and cathepsin G. However, the variety of ANCA antigen specificities contrasts with the fact that the vast majority of ANCA-positive sera are monospecific for a single ANCA antigen. Finally, the fine specificity of granulocyte-specific antinuclear antibodies (GS-ANA) occurring in rheumatoid arthritis and ulcerative colitis is still unknown, but clearly a substantial proportion of GS-ANA belongs to the ANCA family.
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PMID:Antineutrophil cytoplasmic autoantibodies antigen specificity. 171 31

Nicks, or missing peptide linkages, have been found in hCG beta-subunit between residues 44 and 45 and between residues 47 and 48. We examined the occurrence and biological and immunological activities of nicked hCG. As shown by sequence analysis, CR127 standard hCG is approximately 20% nicked, half at beta 44-45 and half at beta 47-48. Treatment with human leukocyte elastase increased the extent of nicking of CR127 standard hCG. The longer the incubation of CR127 standard with human leukocyte elastase (0, 2, and 21 h), the greater the extent of nicked hCG (20%, 46%, and 89%). As the extent of nicking increased, the receptor-binding ability diminished, as did the ability to stimulate progesterone production by rat corpus luteal cells in vitro (0.9, 0.74, and 0.29 microgram/microgram hCG, respectively). In a regression analysis, a linear relationship was indicated between the extent of nicking and receptor binding values (97% correlation) and between the extent of nicking and steroidogenic activity in vitro (99% correlation). From the intercepts of the regression lines, it was estimated that nicks reduced receptor binding by 11-fold and reduced the steroidogenic activity of hCG by 5-fold. We examined eight individual hCG preparations, three purified from pregnancy urine, three from urine from patients with hydatidiform mole, and two from urine from women with choriocarcinoma. In descending order, the eight individual hCG preparations were 100%, 100%, 85%, 76%, 42%, 41%, 0%, and 0% intact. Although no correlation was observed between the percent intact and the ability of the eight individual samples to displace 50% [125I]hCG in binding CG/LH receptor (r less than 0.5), a close correlation was noted between the percent intact and the steroidogenic activity in vitro (98% correlation). This separated the effects of nicking on receptor binding and steroidogenic activities and indicated that while multiple factors influence receptor binding, only nicking suppresses the steroidogenic activity of bound hCG. We examined the recognition of nicked hCG molecules by different hCG immunoassays. The Hybritech Tandem assay measured total hCG and did not distinguish nicked and intact hCG molecules (in a regression analysis, immunoactivity vs. percent intact hCG, r less than 0.5). In contrast, the immunometric assay using B109 hCG dimer-specific monoclonal antibody and anti-beta-peroxidase only detected the intact component of hCG (in a regression analysis, immunoreactivity vs. percent intact hCG, 98% correlation). We used these assays together to estimate the percentage of intact hCG and to deduce the extent of nicking.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The heterogeneity of human chorionic gonadotropin (hCG). III. The occurrence and biological and immunological activities of nicked hCG. 171 36

The antigenic specificity and clinical distribution of the antineutrophil cytoplasmic antibodies (ANCA) in kidney diseases have recently been extensively studied. In patients with systemic vasculitis, the great predominance of two major ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO), is now established. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation, and thus are able to interact with autoantibodies after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, it has been shown that PR3 is identical to myeloblastin, which has been described independently and is involved in the control of growth and differentiation of leukemic cells. Aside from the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been identified, including human leukocyte elastase, lactoferrin, CAP57, and cathepsin G. These rare ANCA specificities occur in a limited number of patients. The variety of ANCA antigen specificities contrasts, however, with the fact that the vast majority of ANCA-positive sera are monospecific for one single ANCA antigen. With regard to clinical distribution, ANCA have major diagnostic significance in the four conditions in which they are frequently detected: Wegener's granulomatosis (WG), Churg and Strauss Syndrome (CSS), microscopic periarteritis (MPA), and necrotic and crescentic glomerulonephritis (NCGN). However, the initial dichotomy between MPO-associated vasculitis (NCGN, MPA) and that associated with anti-PR3 antibodies (WG) appears far from absolute.
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PMID:Antigen specificities and clinical distribution of ANCA in kidney diseases. 172 65

Tannins of natural or synthetic origin are well-known adjuvants in topical anti-inflammatory therapy of skin diseases. In this study, the influence of synthetic tannin on neutrophil accumulation, enzyme release, and on the proinflammatory activity of neutrophil-derived enzymes was investigated. The results show that synthetic tannin (Tamol) specifically inhibits the neutrophil serine protease human leukocyte elastase (HLE) in an irreversible manner with a half-maximal inhibitory concentration (IC50) of 0.3 microgram/ml. Exogenous protein partially abolished the tannin-dependent HLE inhibition (IC50 of Tamol at 1% protein-concentration:1.0 microgram/ml). Synthetic tannin did not influence the activities of other neutrophil enzymes like Cathepsin G, beta-glucuronidase, and myeloperoxidase. The specificity of Tamol for HLE was further substantiated by the lack of inhibition of other serine proteases. Additionally, Tamol had no effect on f-met-leu-phe-induced neutrophil chemotaxis and did not alter enzyme degranulation of neutrophils in response to f-met-leu-phe and opsonized zymosan. We conclude from our results that the anti-inflammatory properties of synthetic tannin may at least in part be due to inactivation of the proinflammatory protease HLE.
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PMID:Selective inactivation of human neutrophil elastase by synthetic tannin. 187 53

Control of myeloperoxidase (MPO) may be an important consideration in disorders where excessive PMN elastase activity is a significant factor. There are, however, two mechanisms for the apparent regulation of MPO: 1) inhibit the enzyme directly, and ii) prevent the ensuing HOC1 induced oxidation by using a surrogate reducing agent. Appropriate methodology has been devised to distinguish true MPO inhibitors. With the exception of NaN3, many MPO inhibitors fall into the latter category and do not actually regulate the enzyme. Several potent organic inhibitors have been discovered, which, because of their structural selectivity, appear to associate specifically with a binding site on the enzyme, rather than attaching indiscriminately to a hydrophobic domain. By controlling the enzyme, these compounds protect alpha-1-PI from MPO induced damage, and could serve better than antioxidants to define the role of MPO in elastase induced injury.
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PMID:Naphthalenes as inhibitors of myeloperoxidase: direct and indirect mechanisms of inhibition. 216 Jan 87

We used antibodies to human leukocyte ("neutrophil") elastase and cathepsin G to localize the corresponding antigens in human neutrophils, monocytes, and alveolar macrophages by immunohistochemistry. Furthermore, we combined immunogold localization with enzyme histochemistry to localize proteinase antigens and endogenous peroxidase activity in the same sections. As expected, all neutrophils contained both elastase and cathepsin G, and the proteinases localized to granules with peroxidase activity. In contrast, marked heterogeneity in monocyte staining for elastase, cathepsin G, and endogenous peroxidase was found. Sixty percent or more were unstained, while the remainder varied greatly in staining intensity. The elastase and cathepsin G in monocytes were localized by immunoelectron microscopy, combined with histochemistry, to cytoplasmic granules which had peroxidase activity. Alveolar macrophages were unstained. Therefore, a subpopulation of peripheral blood monocytes contains leukocyte elastase and cathepsin G in a cell compartment from which these enzymes may potentially be released into the extracellular space. The occurrence of peroxidase and neutral proteinases in the same granules in monocytes could permit the H2O2-myeloperoxidase-halide system and the neutral proteinases to act in concert in such functions as microbe killing and extracellular proteolysis.
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PMID:Elastase and cathepsin G of human monocytes: heterogeneity and subcellular localization to peroxidase-positive granules. 216 60

In serum and sputum samples from 15 patients with cystic fibrosis (CF) suffering from chronic Pseudomonas aeruginosa lung infections, concentrations and/or activities of elastase derived from polymorphonuclear leukocytes (PMN), cathepsin G, myeloperoxidase (MPO), and superoxide dismutase (SOD), as well as concentrations of the proteinase inhibitors alpha 1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M), were determined. High enzyme concentrations compared with those in normal control subjects were found for PMN elastase (mean, 96.1 +/- 91.7 micrograms/ml), cathepsin G (mean, 5.9 +/- 6.0 micrograms/ml), and MPO (mean, 138.0 +/- 177 micrograms/ml) in patients' sputum samples. Superoxide dismutase was not detectable in any of the sputum specimens (below 1 ng/ml). Proteinase inhibitor concentrations were elevated in serum samples (alpha 1-PI: mean, 3,457 +/- 1,084 micrograms/ml; alpha 2-M: mean, 4,835 +/- 1,334 micrograms/ml). Means of 61 +/- 38 micrograms/ml alpha 1-PI and 29 +/- 31 micrograms/ml alpha 2-M were present in the sputum specimens. Both proteinase inhibitors were functional in the serum samples. However, sputum alpha 1-PI was proteolytically degraded, as shown by western blot technique, and was not able to bind 125I-labeled PMN elastase, as shown by autoradiography. Only 10.9 +/- 8.5% of the total alpha 1-PI in the sputum samples was complexed to PMN elastase and 3.6 +/- 3.2% to cathepsin G. On the other hand, 96.2 +/- 96.8% of the total PMN elastase and 78.0 +/- 100% of cathepsin G were unbound in the sputum samples. The study suggests that the imbalance between PMN proteinases and their inhibitors is due to inactivation of alpha 1-PI in the sputum caused by proteolytic or oxidative attack from PMN enzymes.
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PMID:Lysosomal enzymes from polymorphonuclear leukocytes and proteinase inhibitors in patients with cystic fibrosis. 242 73

Nonporous, microparticulate, monodisperse silicas with particle diameters between 0.7 and 2.1 microns are introduced as stationary phases in high-performance affinity chromatography. The immobilization of m-aminophenylboronic acid, p-aminobenzamidine, tri-L-alanine, and concanavalin A onto these silicas was successfully achieved using 3-isothiocyanatopropyl-triethoxysilane as an activation reagent. Immobilized phenylboronic acid was applied to the isolation of nucleosides, nucleotides, and glycoprotein hormones such as bovine follicotropin and human chorionic gonadotropin, while immobilized benzamidine was employed for the isolation of the serine proteases thrombin and trypsin, immobilized tri-L-alanine for the separation of pig pancreatic elastase and human leukocyte elastase, and immobilized concanavalin A for the isolation of horseradish peroxidase. In all affinity chromatographic systems studied, the nonporous monodisperse silicas showed improved chromatographic performance compared to results obtained with porous silica supports using identical activation and immobilization procedures. Furthermore, frontal analysis was used as a method to evaluate the influence of experimental parameters on biological activity and accessible ligand densities. Only minor changes in bioactivity were found with the nonporous affinity supports, where accessibilities were typically higher than ca. 60%. The immobilization of affinity ligands onto porous supports as used in this and associated papers thus represents a successful general procedure for the preparation of stable matrices with fast kinetics for use in high-performance affinity chromatography.
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PMID:High-performance liquid affinity chromatography with phenylboronic acid, benzamidine, tri-L-alanine, and concanavalin A immobilized on 3-isothiocyanatopropyltriethoxysilane-activated nonporous monodisperse silicas. 254 22


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