Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteolytic activities were measured in extracts of human skin melanoma, lymphatic metastasis and in nonmalignant naevi by using various proteinase substrates as well as plasminogen activator assay. pH-optima for hydrolysis of various proteinase substrates by these tumors were found to be essentially the same as in healthy human skin. Melanoma extracts were found to especially readily hydrolyze N-alpha-benzoyl-DL-arginine beta-naphthylamine (BANA) at pH 5.8 in the presence of 1 mmol/l dithiothreitol and EDTA (cathepsin B1-like enzyme) as well as histones and p-tosyl-L-arginine methyl ester (TAME) at pH 7.5, and showed increased capacity to activate plasminogen when compared to nonmalignant naevus. The possible role of proteinases in malignant melanoma is discussed.
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PMID:Proteolytic enzymes and plasminogen activator in melanoma. 3 88

Interactions between tranexamic acid and protein were studied in respect of the antifibrinolytic actions of tranexamic acid. Tranexamic acid did neither show any interaction with fibrinogen or fibrin, nor was incorporated into cross-linked fibrin structure by the action of factor XIII. On the other hand, tranexamic acid bound to human plasmin with a dissociation constant of 3.5 X 10-5 M, which was very close to the inhibition constatn (3.6 X 10-5 M1 for this compound in inhibiting plasmin-induced fibrinolysis. The binding site of tranexamic acid on plasmin was not the catalytic site of plasmin, because TLCK-blocked plasmin also showed a similar affinity to tranexamic acid (the dissociation constant, 2.9-4.8 x 10-5m). in the binding studies with the highly purified plasminogen and TLCK-plasmin preparations which were obtained by affinity chromatography on lysine-substituted Sepharose, the molar binding ratio was shown to be 1.5-1.6 moles tranexamic acid per one mole protein. On the basis of these and other findings, a model for the inhibitory mechanism of tranexamic acid is presented.
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PMID:Plasminogen-plasmin system IX. Specific binding of tranexamic acid to plasmin. 12 63

The third component of complement has been purified from fresh human plasma employing an initial fractionation with poly(ethylene glycol) followed by sequential depletion of plasminogen by affinity adsorbents, chromatography on diethylaminoethylcellulose, gel filtration on agarose, and batch adsorption/desorption on hydroxylapatite. Final recoveries of C3 were 33% of the initial protein, as quantitated by radial immunodiffusion, and 31% of the initial hemolytic activity. Apparent homogeneity is indicated by immunological criteria and by polyacrylamide gel electrophoresis. A partial specific volume of 0.736 +/- 0.003 mlgm-1 was determined for C3 by the mechanical oscillator technique. "Low speed" sedimentation equilibrium yielded an apparent weight average molecular weight for the protein of 187 650 +/- 5650. Based upon this molecular weight, a molar extinction coefficient of 1.82 X 10(5) 1. mole-1 cm-1 at 280 nm was calculated from boundary-spreading experiments in the ultracentrifuge and as assumed refractive index increment. Amino acid analyses revealed no unusual or distinctive characteristics. Automated Edman degradation revealed a double N-terminal sequence, Ser-Val,Pro-Glx,Met-Lee,Tyr-Thr,Ser-Glx,Ile-Lys,Gly-Arg,Thr-Met,Pro-Asx, in agreement with the two chain structure observed on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and revealing both chains are available to degradation. Serine is postulated as the initiating sequence in both chains based upon high recoveries of dinitrophenylserine upon hydrolysis of dinitrophenylated C3, and our inability to identify any other dinitrophenyl or phenylthiohydantoin derivatives in this position. Alanine is the ultimate carboxy-terminal amino acid of at least one of the chains, as indicated by the action of carboxypeptidases on C3 in the presence of sodium dodecyl sulfate.
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PMID:Third component of human complement: purification from plasma and physicochemical characterization. 82 64

Cross-linked hybrid oligomers of fibrinogen and fibrin are found in plasma from fibrinaemic patients and normal individuals as well as in preparations of purified human fibrinogen. The present study was undertaken to see if such hybrid oligomers have the same stimulatory effect on tissue plasminogen activator (t-PA) conversion of plasminogen as do polymeric and monomeric fibrin. Hybrid oligomeric fibrin(ogen) material was provided by subjecting purified human fibrinogen to gel filtration in urea-containing buffer at pH 5.6. Well separated fractions of hybrid oligomeric material and monomeric fibrinogen were thus obtained. Some of this material was converted to soluble polymeric or monomeric fibrin using insolubilized thrombin. Hybrid polymeric fibrin, polymeric fibrin or monomeric fibrin were then added to citrated, normal plasma to 2.5 or 5 per cent of the plasma fibrinogen concentration. The added material was kept in solution by plasma fibrinogen. The "COA-SET Fibrin Monomer Test" (Kabi,Stocholm,Sweden), based on the ability of fibrin monomers to enhance t-PA mediated plasminogen-plasmin conversion, was used to compare the potential stimulatory effect of the preparations above. The results led to the following conclusions: 1) Cross-linked, soluble fibrin(ogen) hybrid polymers in a concentration of 5 per cent of plasma fibrinogen concentration (w/w) do not stimulate t-PA. 2) Thrombin conversion of the fibrin-fibrinogen hybrid material resulted in an increase in the rate of t-PA mediated plasminogen conversion, corresponding to the one observed with equivalent (w/w) amounts of fibrin monomers. Compared on a mole to mole basis, fibrin oligomers are more powerful than fibrin monomers as stimulators of t-PA activity.
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PMID:Soluble, cross-linked fibrin(ogen) hybrid oligomers do not stimulate t-PA conversion of plasminogen. 141 94

The ability of the COA-SET Fibrin monomer (COA-SET FM) test to detect soluble fibrin was evaluated by comparing the results of the COA-SET FM test with fibrinopeptide A (FPA) determinations following thrombin incubation of plasma or whole blood. In addition, two semiquantitative tests (erythrocytes-agglutination test (FM-test) and ethanol gelation test (EGT] were included in the study. Under the experimental conditions used, the COA-SET FM test proved less sensitive than the FPA-assay. There was a strong correlation between the results obtained by the two tests (r = 0.86, p = 0.0001). When solely regarding low levels of soluble fibrin, however, the correlation was weaker (r = 0.59, p = 0.0003). The FM-test was less sensitive than the COA-SET FM test, but more sensitive than EGT at normal and low fibrinogen concentrations. At high fibrinogen concentrations, however, EGT proved more sensitive than the FM-test. Knowing that 1-2 moles of FPA are released per mole of fibrin monomers formed, a discrepancy was observed between the FPA concentrations and the fibrin monomer concentrations as determined by the COA-SET FM test, the FPA levels being 2-25 times higher than the fibrin monomer levels. The discrepancy was greatest at incipient fibrinogen-fibrin transformation and at high plasma fibrinogen levels. This may suggest that fibrinogen in some way interfered with the stimulating effect of fibrin on the t-PA catalyzed activation of plasminogen, the principle upon which the COA-SET FM test is based.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of methods for detecting soluble fibrin in plasma. An in vitro study. 232 70

Low molecular weight two-chain urokinase is a 33-kD plasminogen activator, which has no innate affinity for fibrin and consequently, its use to facilitate lysis of blood clots may lead to systemic activation of plasminogen. In order to impart clot affinities to this urokinase form (UK) we have generated two novel fibrin-binding derivatives by partially reducing UK and exchanging the native disulfide-linked peptide A with peptide A analogs. The peptide A analogs contained the fibrin-adherent fibrin-derived sequences, GPRP (derived from positions 17-20 of the fibrinogen alpha chain) or QAGDV (407-411 sequence of the fibrinogen gamma chain), each coupled through amino-hexanoic acid to a synthetic peptide, LKFQCGQK, containing the Leu 144-Lys 158 sequence of the urinary plasminogen activator A Chain. The resultant derivatives contained about 0.4 moles peptide analog/mole UK, were 75% active toward synthetic UK substrates, and were recovered in a nearly 80% yield. The two fibrin peptide derivatives had a five-fold greater affinity for the clots.
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PMID:Insertion of fibrin peptides into urokinase enhances fibrin affinity. 235 45

We have investigated the interaction of alpha 2-macroglobulin (alpha 2M) with the serine proteinase urokinase, an activator of plasminogen. Urokinase formed sodium dodecyl sulfate stable complexes with purified alpha 2M and with alpha 2M in plasma. These complexes could be visualized after polyacrylamide gel electrophoresis by protein blots using 125I-labeled anti-urokinase antibody or by fibrin autography, a measure of fibrinolytic activity. According to gel electrophoretic analyses under reducing conditions, urokinase cleaved alpha 2M subunits and formed apparently covalent complexes with alpha 2M. Urokinase cleaved only about 60% of the alpha 2M subunits maximally at a mole ratio of 2:1 (urokinase: alpha 2M). Binding of urokinase to alpha 2M protected the urokinase active site from inhibition by antithrombin III-heparin and inhibited, to a significant extent, plasminogen activation by urokinase. Reaction of urokinase with alpha 2M caused an increase in intrinsic protein fluorescence and, thus, induced the conformational change in alpha 2M that is characteristic of its interactions with active proteinases. Our results indicate that both in plasma and in a purified system the alpha 2M-urokinase reaction is functionally significant.
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PMID:Structural and functional characterization of the inhibition of urokinase by alpha 2-macroglobulin. 241 80

Dermal nevocytic nevi (NN) were histochemically studied with the help of FITC-conjugated lectins as well as antisera against keratin and plasminogen activators of the urokinase type. 3 out of 18 NN showed interpenetrating nevus cells in atrophic parts of the epidermis. These cells revealed strong lectin reactivity both with Con A (cytoplasmatic binding) and WGA/RCA II (membraneous binding). In addition we found membraneous reaction with anti-urokinase, whereas there was no anti-keratin staining. Our findings suggest active transepidermal elimination of nevus cells in dermal nevocytic nevi.
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PMID:[Histochemical studies of transepidermal elimination of nevus cells in nevus cell nevi of the corium]. 247 58

The ability of the native form of plasminogen (Glu-plasminogen) to form complexes with fibrinogen and its fragments immobilized on CNBr-agarose was studied. It was found that unlike Lys-plasminogen, the native form of the proenzyme does not bind to fibrinogen agarose. Limited proteolysis of fibrinogen by plasmin involving alpha C-domains results in the appearance of Glu-plasminogen binding sites at fibrinogen surface. The X2 fragment of fibrinogen binds to about 0.5 moles of Glu-plasminogen at an equimolar ratio of the interacting proteins. Under these conditions, the amount of bound Glu-plasminogen does not increase as a result of subsequent hydrolysis of fibrinogen down to end products, fragments E and D. It was found that Glu-plasminogen interacts with both E- and D-fragments of fibrinogen. Similar to Lys-plasminogen, Glu-plasminogen exhibits a high affinity for the E-fragment. The maximal quantity of the bound protein under the given experimental conditions is 2 moles per mole of the immobilized E-fragment. The interaction of Glu-plasminogen with the E-fragment is mediated by the lysine-binding sites of the proenzyme with a high and low affinity [Kd = 1.8.10(-6) and 7.5.10(-5) M, respectively]. Glu-plasminogen, unlike Lys-plasminogen, shows a low affinity for the D-fragment (Kd = 2.10(-5) M). Glu-plasminogen cannot be adsorbed by arginine-binding sites at the DH fragment-agarose.
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PMID:[Binding of Glu-plasminogen by fibrinogen and byproducts of its proteolysis]. 252 32

The lytic therapy using Urokinase (UK) as well as Streptokinase (SK) has a significant risk of complications such as systemic bleeding. We aimed to develop the autologous plasmin (AP) solution as a potential lytic agent and to evaluate its lytic efficacy. Method; The AP solution was aseptically prepared by adding UK to autologous plasma separated by centrifugation (at 4 degrees C, 3,000 rpm, 10 min). The induced plasmin activity of the AP solution was measured by plasminogen-free fibrin plate method and spectrophotometric method with substrate S-2251. In vitro study, we made a fibrin clot by adding CaCl2 (1/40 mole, 0.2 ml) to autologous plasma (0.2 ml). The clot weight was measured before and after incubation for 60 min at 37 degrees C to estimate the lytic effects of the AP solution and the UK solution. In animal study, femoral artery of anesthetized mongrel dogs (n = 20) was narrowed by ligation (1 mm in diameter) and the fibrin clot was embolized into this portion. AP (n = 8), UK (n = 6) or saline (n = 6) was selectively injected for 3 min into the arterial lumen, after the temporary flow obstruction was completed by inflation of balloon tip catheter located proximal to the embolized site of the artery. Lytic effects on the embolized fibrin clot were sequentially observed by the extra-vascular ultrasound flow meter (equipped with pencil probe) for 60 min. For this study, the AP solution was prepared by adding dose of 12,000 IU/ml of UK. The same dose of the UK solution was also used as a control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The potential thrombolysis under selective infusion of the autologous plasmin (AP) solution]. 296 1


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