Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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

Neutrophil elastase and myeloperoxidase probably play an important role in the development of pulmonary emphysema. We have analyzed drugs from the major classes of agents that alter neutrophil function to determine if there are drugs in use today that can reduce the load of neutrophil elastase or myeloperoxidase in the lungs of smokers. Eleven representative drugs were tested for their ability to inhibit chemotaxis and degranulation. None of the drugs inhibited chemotaxis in a dose-response fashion at concentrations achievable in human plasma. Sulfinpyrazone, phenylbutazone, and auranofin completely inhibited the release of azurophilic granules (myeloperoxidase) and tertiary granules (beta-D-glucuronidase) when formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) was used as the stimulant, and inhibited azurophilic granule release by 69%, 19%, and 64% respectively, but not tertiary granule release when macrophage-conditioned media was used as the stimulus. In conclusion, none of the drugs tested are inhibitors of chemotaxis; however, three are excellent inhibitors of azurophilic granule enzyme release. Of these three, sulfinpyrazone, a drug that is not currently used clinically for its antiinflammatory effects, is the least toxic and should be considered as a potential drug to reduce the elastase and myeloperoxidase load in the lungs of smokers who are developing emphysema.
 ...
PMID:Search for drugs that may reduce the load of neutrophil azurophilic granule enzymes in the lungs of patients with emphysema. 254 34

Bacteria and the inflammatory response they engender are implicated in the pathophysiology of premature rupture of fetal membranes and preterm birth. We tested the hypothesis that bacteria and polymorphonuclear neutrophils may have both separate and combined effects in weakening the amniochorionic membrane, and thus predispose to premature rupture of membranes. We examined how three parameters of membrane integrity (bursting tension, work to rupture, and elasticity) were affected by standardized preparations (10(9) cfu/mL) of group B streptococci or Staphylococcus aureus in the presence or absence of purified human neutrophils (32 x 10(6)/mL). In addition, effects of purified human neutrophil elastase were evaluated. Exposure to either group B streptococcus or S aureus decreased membrane strength, elasticity, and work to rupture. Only activated neutrophils had significant effects on membrane strength. Membrane exposure to S aureus plus neutrophils led to an additive weakening of fetal membranes. On the other hand, group B streptococci did not interact with neutrophils to yield a significant further weakening of the membranes. Elastase (150 U/mL) also weakened the membrane. The results were correlated with measures of protease (Azocoll and ninhydrin assays) and peroxidase (dimethoxybenzidine) activity. Our findings support the concept that human neutrophils and their constituent enzymes may act in concert with bacteria and their protease(s) in weakening amniochorion, and may possibly predispose to premature rupture of membranes in some women. These observations require clinical correlations.
 ...
PMID:Bacteria and inflammatory cells reduce chorioamniotic membrane integrity and tensile strength. 255 66

Tumor necrosis factor (rTNF) has previously been shown to induce PMN chemotaxis, stimulate PMN adhesion to vascular endothelium and stimulate hydrogen peroxide secretion from PMNs adhered to biological surfaces. We investigated the activity of both rTNF alpha and rTNF beta on adherent and suspension cultures of human PMNs. rTNF alpha selectively stimulated the release of the specific granule in a dose dependent manner. Exocytosis of the specific granule was measured with an enzyme-immunoassay for lactoferrin and a radioassay for vitamin B12-binding protein. Adherent PMNs released up to 60% of the total lactoferrin content of the cells with no increase in myeloperoxidase (MPO) secretion when stimulated with 0.1-10 nM rTNF alpha. The PMNs in suspension cultures also selectively released the specific granule, although total release was reduced suggesting that adherence of PMNs increased their ability to respond to physiological stimuli. When PMNs in suspension cultures or adherent cells were stimulated with rTNF alpha, no LTB4 production was detectable, yet the cells retained the ability to synthesize LTB4 when stimulated with calcium ionophore A23187. Neither rTNF alpha or rTNF beta stimulated the release of the azurophilic granule, measured by the secretion of MPO and neutrophil elastase activity. These results suggest that a function of rTNF alpha and rTNF beta on PMNs is the release of the contents within the specific granule.
 ...
PMID:Effect of tumor necrosis factor on granule release and LTB4 production in adherent human polymorphonuclear leukocytes. 255 73

Although the etiology of rheumatoid interstitial lung disease (RILD) remains unknown, bronchoalveolar lavage (BAL) has been useful in studying potentially pathogenic mechanisms in this disorder. Previous investigations in patients with rheumatoid arthritis (RA) and RILD revealed abnormal BAL T-lymphocyte subpopulations and a significant elevation in BAL neutrophils. Because neutrophils have been implicated as important effector cells in inflammatory disorders such as ARDS and idiopathic pulmonary fibrosis, we evaluated BAL fluid in patients with RA for neutrophil chemotactic and activating properties and for evidence of neutrophil activation. The BAL fluid from patients with RILD contained significant neutrophil chemotactic activity derived from both lipid and nonlipid components. Evidence for neutrophil stimulation in the lower respiratory tract of patients with RILD was suggested by elevations in both myeloperoxidase activity and immunologically determined levels of human neutrophil elastase in BAL fluid. Free uninhibited elastolytic activity, however, was not demonstrated, suggesting that adequate protease inhibitor levels were present to inhibit active elastase activity. In addition to elevated myeloperoxidase activity, a potential role for neutrophil-derived oxidant injury was indirectly suggested by the enhanced release of superoxide anion (O2-) from resting normal human blood neutrophils challenged with concentrated BAL fluid from patients with RA and interstitial lung disease. Significant correlations were found between physiologic parameters and the percentage of BAL neutrophils, as well as levels of neutrophil-derived mediators. For example, levels of human neutrophil elastase were strongly correlated with diminished diffusion capacity (r = -0.73, p less than 0.001) and reduced forced vital capacity (r = -0.63, p less than 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lower respiratory tract abnormalities in rheumatoid interstitial lung disease. Potential role of neutrophils in lung injury. 282 54

The gene for human neutrophil elastase (NE), a powerful serine protease carried by blood neutrophils and capable of destroying most connective tissue proteins, was cloned from a genomic DNA library of a normal individual. The NE gene consists of 5 exons and 4 introns included in a single copy 4-kilobase segment of chromosome 11 at q14. The coding exons of the NE gene predict a primary translation product of 267 residues including a 29-residue N-terminal precursor peptide and a 20-residue C-terminal precursor peptide. Analysis of the N-terminal peptide sequence suggests it contains a 27-residue "pre" signal peptide followed by a "proN" dipeptide, similar to that of other blood cell lysosomal proteases. The sequences for the mature 218-residue NE protein are included in exons II-V. The 5'-flanking region of the gene includes typical TATA, CAAT, and GC sequences within 61 base pairs (bp) of the cap site. The sequence 1.5 kilobases 5' to exon I contains several interesting repetitive sequences including six tandem repeats of unique 52- or 53-bp sequences. The 5'-flanking region also contains a 19-bp segment with 90% homology to a segment of the 5'-flanking region of the human myeloperoxidase (MPO) gene, a gene also expressed in bone marrow precursor cells and a protein stored in the same neutrophil granules as NE. In addition, like the MPO gene, the NE 5'-flanking region has several regions with greater than or equal to 75% homology to sequences 5' to c-myc, but there is no overlap between the NE-c-myc and MPO-c-myc homologous sequences.
 ...
PMID:Structure of the human neutrophil elastase gene. 290 87

Alpha-1-proteinase inhibitors (alpha 1PI) containing methionine (Met-358) or valine (Met----Val-358) at the reactive center were synthesized in and purified to homogeneity from recombinant yeast. The pure proteins were exposed to 1 of 4 different oxidizing systems: N-chlorosuccinimide (chemical oxidation), myeloperoxidase plus peroxide and halide (enzymatic oxidation), activated neutrophils (cellular oxidation), or gas-phase cigarette smoke. The effect of these treatments on the leukocyte elastase inhibitory function of both proteins was then assessed. After brief exposures, substantial inactivation of the normal inhibitor occurred, whereas the mutant inhibitor remained fully active. More prolonged exposures led to complete inactivation of the normal protein and partial inactivation of the mutant inhibitor. These results suggest that the reactive center methionyl residue in alpha 1PI is more rapidly affected by oxidants than are other oxidizable residues in the inhibitor; however, Met-358 is not the only residue in alpha 1PI whose modification can lead to the inactivation of the elastase inhibitory capacity of this protein.
 ...
PMID:A genetically engineered, mutant human alpha-1-proteinase inhibitor is more resistant than the normal inhibitor to oxidative inactivation by chemicals, enzymes, cells, and cigarette smoke. 300 58

Plasma C3a and C5a levels as well as plasma levels of granulocyte lactoferrin, granulocyte myeloperoxidase and granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) were investigated in 10 patients (52.7 +/- 5.9 years) undergoing maintenance hemodialysis (39.4 +/- 12.4 months) with hollow fiber dialyzers made from polymethylmethacrylate. Plasma levels of lactoferrin increased from 166.5 +/- 28.5 to 712.5 +/- 165.9 ng/ml, myeloperoxidase from 59.0 +/- 15.3 to 210.5 +/- 33.9 ng/ml and E-alpha 1PI from 114.2 +/- 18.1 to 681.8 +/- 102.6 ng/ml during dialysis. In contrast, plasma C3a levels rose from 179.8 +/- 33.6 to maximal 276.2 +/- 45.4 ng/ml and C5a from 55.7 +/- 8.1 to maximal 101.1 +/- 14.8 ng/ml. Our data indicate that degranulation of granulocytes occurs during dialysis despite only little complement activation and mild initial granulocytopenia.
 ...
PMID:Different complement and granulocyte activation in patients dialyzed with PMMA dialyzers. 301 63

Plasma levels of granulocyte lactoferrin, granulocyte myeloperoxidase and granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) were investigated in regular hemodialysis patients dialyzed with hollow-fiber dialyzers made from polycarbonate (FD 100) or cuprophan (GFS 120 H). Plasma levels of all these main granulocyte components increased significantly during hemodialysis. E-alpha 1PI levels were significantly higher in patients dialyzed with the polycarbonate compared with the cuprophan membrane, whereas the increases of myeloperoxidase and lactoferrin were not different for the two dialyzers. On the other hand, plasma C3a levels were higher in patients dialyzed with the cuprophan compared with the polycarbonate dialyzer. Therefore, granulocyte activation during hemodialysis does not necessarily need complement activation.
 ...
PMID:Plasma levels of main granulocyte components in patients dialyzed with polycarbonate and cuprophan membranes. 303 92

Oxidant species produced by human polymorphonuclear leukocytes (PMN) inactivate alpha-1-protease inhibitor and thus may indirectly enhance neutrophil elastase-induced proteolysis. It is unclear, however, if PMN-derived oxidants directly enhance proteolysis of extracellular matrix by neutrophil elastase. Matrix was produced by neonatal rat aortic smooth muscle cells and pulse-labeled with 3H-lysine to allow identification of the collagen-specific amino acid, hydroxylysine (3H-HL), and the elastin specific amino acid, desmosine (3H-DES). The smooth muscle cells were lysed, and the remaining matrix was used as a culture surface and a proteolytic substrate for intact PMN and purified neutrophil elastase. Proteolysis of collagen and elastin were quantified by chromatographic separation of the marker amino acids 3H-HL and 3H-DES, which were released into the supernatant or remained in the matrix after a 3-h incubation at 37 degrees C. The peptide, formyl-methionine-leucine-phenylalanine (FMLP), produced more rapid release of myeloperoxidase than did phorbol myristate acetate (PMA), which produced more release of O2- and H2O2 than did FMLP. The percent release of total matrix 3H-DES in the presence of PMN + FMLP was 2.45 +/- 0.19% (mean +/- SE, n = 6) and with PMN + PMA it was 1.32 +/- 0.1% (n = 6, p less than 0.01). The release of matrix 3H-HL did not differ. Neutrophil cytoplasts, which produced O-2 and H2O2 but lacked azurophilic granules, did not significantly enhance either elastin or collagen degradation by purified neutrophil elastase (NE).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Direct effects of neutrophil oxidants on elastase-induced extracellular matrix proteolysis. 303 75


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