Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cervical maturation, dilatation and uterine contraction in imminent premature delivery are closely related to chemical mediators from activated granulocytes which infiltrate into the cervix. It is known that urinastatin (urinary trypsin inhibitor, UTI) inhibits many kinds of chemical mediators from granulocytes and macrophages such as granulocyte elastase (elastase) and interleukin 1. We examined the effect of a UTI suppository on uterine contraction and the elastase level in cervical mucus in cases of imminent premature delivery. We treated 43 cases of imminent premature delivery with tocolysis index 3 or 4 with 4 kinds of therapy: Group A (N = 12): ritodorine drop infusion therapy; Group B (N = 9): daily UTI suppository (1,000U) therapy; Group C (N = 14): daily UTI suppository + ritodorine drop infusion therapy; Group D: daily UTI suppository + ritodorine drop infusion + antibiotics (oral cepharosporine) therapy. The elastase level of cervical mucus before treatment was 0.76 +/- 0.40 micrograms/ml in group A, 0.93 +/- 0.43 micrograms/ml in group B, 0.85 +/- 0.40 micrograms/ml in group C and 0.90 +/- 0.41 micrograms/ml in group D. There was no significant difference between these groups. The elastase level in cervical mucus was 0.75 +/- 0.47 micrograms/ml in group A, 0.27 +/- 0.35 micrograms/ml in group B, 0.27 +/- 0.33 micrograms/ml in group C and 0.30 +/- 0.19 micrograms/ml in group D, respectively. The elastase level was decreased significantly in groups B, C and D. The time taken to depress uterine contraction was 65 +/- 66 min in group A, 375 +/- 336 min in group B, 70 +/- 64 min in group C and 58 +/- 53 min in group D, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The effect of granulocyte elastase inhibitor (urinastatin) vaginal suppository on patients with imminent premature delivery]. 134 16

Inhibitors of human neutrophil elastase were engineered by designing and producing a library of phage-displayed protease inhibitory domains derived from wild-type bovine pancreatic trypsin inhibitor and fractionating the library for binding to the target protease. The affinity of one of the engineered variants for human neutrophil elastase (Kd = 1.0 pM) is 3.6 x 10(6)-fold higher than that of the parental protein and exceeds the highest affinity reported for any reversible human neutrophil elastase inhibitor by 50-fold. Thus the display phage method has allowed us to obtain protein derivatives that exhibit greatly increased affinity for a predetermined target. The technology can be applied to design high-affinity proteins for a wide variety of target molecules.
 ...
PMID:Directed evolution of a protein: selection of potent neutrophil elastase inhibitors displayed on M13 fusion phage. 154 6

We have developed a method for electrotransfer of strongly basic proteins (lysozyme, pI 11; mucus proteinase inhibitor, pI greater than 10; bovine pancreas trypsin inhibitor; pI 10.5; human leukocyte elastase, pI greater than 9) from nondenaturing acid gels (pH 4.5) to nitrocellulose sheets. Buffers were those used in a discontinuous system for transfer from sodium dodecyl sulfate (SDS)-containing polyacrylamide gels with one modification in the cathode buffer which contained 0.1% SDS. This method was compared to electrotransfer performed in 0.7% acetic acid. The basic proteins studied, which were positively charged in the gel, formed with SDS negative complexes which migrated toward the anode and were efficiently transferred to the nitrocellulose. Moreover, their biological properties were preserved: inhibitory activity, enzyme activity, and antigenicity. This method is advantageous because it is simple, is sensitive, and can be applied to various biological fluids to detect inhibitors, enzymes, and other proteins which have a basic character, after electrophoretic separation under their native forms.
 ...
PMID:Electrotransfer of basic proteins from nondenaturing polyacrylamide acid gels to nitrocellulose: detection of enzymatic and inhibitory activities and retention of protein antigenicity. 169 33

Three structurally related but functionally different serpins from horse plasma were isolated and characterized. In spite of their identical N-terminal sequences, which show some similarity to that of human alpha 1-proteinase inhibitor, the reactive-centre loops of each of these proteins show extensive variation. Only inhibitor I, with a P1 methionine residue, resembles human alpha 1-PI with regard to (a) similarity of amino acid sequence in the vicinity of the reactive-site peptide bond, (b) broad inhibitory specificity, (c) sensitivity to oxidative inactivation and (d) high rate of reactivity with neutrophil elastase(s). Inhibitor II, with a P1 arginine residue, is an exclusive trypsin inhibitor, and inhibitor III is an oxidation-resistant slow-reacting elastase inhibitor with a P1 alanine residue. Comparison of association rate constants for the inhibition of horse neutrophil elastases by the three inhibitors indicates that only inhibitor I is likely to be physiologically important in the regulation of these enzymes.
 ...
PMID:Comparative properties of three functionally different but structurally related serpin variants from horse plasma. 200 10

Variants of human secretory trypsin inhibitor were constructed with the aim of producing inhibitors specific for human leukocyte elastase. Models of the hPSTI/HLE and hPSTI/chymotrypsin complexes were generated by computer aided protein design and used to plan better HLE inhibitors. This resulted in the production of the strongest and most specific inhibitors of HLE known.
 ...
PMID:Human leukocyte elastase inhibitors: designed variants of human pancreatic secretory trypsin inhibitor (hPSTI). 240 May 89

A synthetic gene encoding the protein sequence of mature bovine pancreatic trypsin inhibitor (BPTI) has been cloned into a novel E. coli expression vector. After in vitro gene amplification by successive DNA duplications, more than 600 000 mostly inactive inhibitor molecules may be recovered from a single cell. After purification the inhibitory activity can be reconstituted almost completely. The specificity of BPTI for trypsin is abolished by a single amino acid exchange from lysine to isoleucine at position 15. The altered protein is shown to be an efficient inhibitor of human leukocyte elastase.
 ...
PMID:A synthetic operon containing 14 bovine pancreatic trypsin inhibitor genes is expressed in E. coli. 243 25

The conversion of inter-alpha-trypsin inhibitor (I alpha I) into active, acid-stable derivatives by proteolytic degradation has been tested with 10 different proteinases. Of these, only plasma kallikrein, cathepsin G, neutrophil elastase, and the Staphylococcus aureus V-8 proteinase were found to be effective, each releasing more than 50% of this activity. However, a strong correlation between inhibitor degradation and significant release of acid-stable activity could only be found with the V-8 enzyme. Inhibition kinetics for the interaction of native I alpha I, the inhibitory fragment released by digestion with S. aureus V-8 proteinase, or the related urinary trypsin inhibitor, with seven different proteinases indicated that all had essentially identical Ki values with an individual enzyme and, where measurements were possible, nearly identical second order association rate constants. Significantly, none of the five human proteinases tested, including trypsin, chymotrypsin, plasmin, neutrophil elastase, and cathepsin G, would appear to have low enough Ki values to be physiologically relevant. Thus, the role of native I alpha I or its degradation products in controlling a specific proteolytic activity is still unknown.
 ...
PMID:Inter-alpha-trypsin inhibitor. Inhibition spectrum of native and derived forms. 247 94

Bovine pancreatic trypsin inhibitor (BPTI, also known as aprotinin or Kunitz inhibitor, a mini-protein composed of 58 amino-acid residues, containing a single methionine residue at position 52) has been selectively oxidized by treatment with chloramine T, under mild conditions, to the methionyl sulfoxide derivative. Spleen inhibitor II (SI II, an isoform of BPTI containing two methionine residues at positions 18 and 52) has been oxidized under the same conditions. Oxidation affects the functional properties of the two inhibitors differently: the antiproteolytic activity of BPTI towards bovine trypsin and chymotrypsin, porcine kallikrein and human leukocyte elastase is not changed upon oxidation, while in the oxidized SI II, the affinity for both chymotrypsin and elastase decreases, with respect to the native protein. These results have been directly related to the oxidation of Met18 in SI II, located at the P'3 site in the contact area with the proteases.
 ...
PMID:Selective oxidation of methionine residues in Kunitz-type protease inhibitors. 247 60

Using the solid-phase procedure an analog of trypsin inhibitor CMTI III containing Val5 instead of Arg5 in position P1, was synthesized. The substitution in only this one position P1 increased the affinity of synthetic inhibitor to porcine pancreatic elastase and human leukocyte elastase by the factor of 10(3) and 10(7), respectively.
 ...
PMID:Synthesis of an elastase inhibitor by monosubstitution of arginine-5 with valine at the reactive site in a trypsin inhibitor from squash seeds (CMTI III). 274 57

Strong activity of acid-stable trypsin inhibitor (ASTI) was confirmed in some clinical thrombin preparations. Thrombin preparations of human plasma origin had no detectable ASTI activity, whereas some preparations of bovine plasma origin revealed more than 5,000 U/vial (5,000 thrombin units), indicating a higher content of ASTI than of thrombin in terms of protein concentration. Contamination by other biologically active substances was also suggested by variations in amidolytic activity with several synthetic substrates (S-2238, S-2251, S-2444, S-2266 and Bz-L-Arg-pNA). On isoelectric focussing, the ASTI activities migrated in acidic positions with pI values of 3.9, 4.5, 5.0, 5.9 and 6.5, respectively. They were almost parallel to the thrombin Bz-L-Arg-pNA hydrolytic activity, and differed from that of the purified thrombin preparation (pI = 7.0). By gel filtration on Sephadex G-100, the molecular weights of the inhibitors as calculated using standard proteins were 140,000 (main), 70,000 and less than 10,000 (minor), respectively. An immunological difference between the main inhibitor (pI = 3.9, mol wt 140,000) and previously reported plasma ASTI was also confirmed with goat anti-UTI serum by the double immunodiffusion and ELISA methods. The inhibitor exerted a strong inhibitory effect not only on trypsin and chymotrypsin, but also on non-plasmic fibrinolysis with human leukocyte elastase, and to a lesser extent on the blood coagulation system (lengthening of APTT and PT). Clearly, when using thrombin preparations and analyzing the data obtained after their administration, the effects of this and other contaminant biologically active substances must be taken into account.
 ...
PMID:Strong activity of acid-stable trypsin inhibitor in bovine thrombin for clinical use. 314 Oct 90


1 2 3 4 5 6 7 Next >>