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

---

Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunochemical specificity of rabbit antisera to human fibrinopeptide-B (FPB) has been studied by comparing the relative abilities of FPB and of various proteins and peptides containing the NH2-terminal segment of the B beta-chain of human fibrinogen to inhibit the binding of a radioiodinated FPB derivative by each of seven anti-FPB sera. Anti-FBP sera varied in the extent to which they cross-reacted with fibrinogen, the NH2-terminal disulfide knot of fibrinogen (N-DSK), B beta 1(Pyr)-118(Met), B beta 1(Pyr)-42(Arg), and desarginyl-FPB. Anti-FPB sera have been identified that discriminate effectively between FPB and larger FBP-containing peptides; such antisera can be used to measure FPB in the absence of the larger peptides or to demonstrate the presence of larger peptides such as B beta 1(Pyr)-42(Arg) in extracts of clinical plasma samples by means of an increase in FPB immunoreactivity following thrombin treatment. One anti-FPB serum has been identified that is capable of detecting desarginyl-FPB, and this antiserum has been used in the development of a radioimmunoassay for desarginyl-FPB. Thus, by precisely defining the specificity of anti-FPB sera, it has been possible to identify antisera that are useful, not only in the measurement of FPB, but also in the detection of other important related molecules, such as B beta 1(Pyr)-42(Arg) and desarginyl-FPB. The immunochemical detection of these FPB-related peptides should provide useful information concerning the action of proteolytic enzymes, such as plasmin on the NH2-terminal segment of the B beta-chain of fibrinogen, and of carboxypeptidase-B on free FPB, in human plasma.
...
PMID:Immunochemical studies of antisera to human fibrinopeptide-B. 617 83

Plasma concentrations of thrombin sensitive peptide fibrinopeptide A (FpA), plasmin sensitive fibrinogen fragment B beta 1-42 and the platelet release product beta-thromboglobulin (beta TG) have been measured in 36 patients before and after total hip replacement. Statistically significant elevations of all three activation products were observed in the days following operation. There were small differences in plasma concentrations of FpA, B beta 1-42 and beta TG in patients who did (n = 13) and did not (n = 23) develop post operative deep vein thrombosis, as assessed by ascending venography on post operative day 10, but these differences were not statistically significant. It is concluded that coagulation and fibrinolytic systems and also blood platelets are activated following total hip replacement operations. However, the formation of post operative deep vein thrombosis can not be effectively monitored by measurement of the activation products.
...
PMID:Plasma concentrations of fibrinopeptide A, fibrinogen fragment B beta 1-42 and beta-thromboglobulin following total hip replacement. 618 May 1

The kinetics of inhibition of human and bovine alpha-thrombin and human factor Xa by antithrombin III were examined under pseudo-first-order conditions as a function of the concentration of pentosan polysulphate [a fully sulphated (beta 1-4)-linked D-xylopyranose with a single laterally positioned 4-O-methyl-alpha-D-glucuronic acid]. Double-reciprocal plots of the observed first-order rate constant against concentration of pentosan polysulphate gave straight lines, intercepts on the axes giving values for maximum increase in second-order rate constant (by calculation) and apparent dissociation constant. These values were: for human alpha-thrombin 1.52 X 10(7) M-1 . min-1 and 3.6 microM respectively, for bovine alpha-thrombin 6.56 X 10(6) M-1 . min-1 and 0.16 microM and for factor Xa 6.86 X 106 M-1 . min-1 and 20 microM. In the presence of pentosan polysulphate the dissociation constant for the initial complex of antithrombin III and thrombin was shown to be reduced from approx. 2 X 10(-3) M to 61 X 10(-6) M without apparent change in the limiting rate constant of 750 min-1. An oligosaccharide (primarily 8-10 saccharide units) prepared from heparin and with high affinity for antithrombin III but low potency in the thrombin-antithrombin III interaction did not diminish the rate of interaction catalysed by pentosan polysulphate. The catalysis was shown to be due to a weak electrostatic interaction, since it was completely reversed by concentrations of NaCl greater than 0.3 M. It is concluded that the mechanism is independent of the heparin high-affinity binding site on antithrombin III and is probably due to binding of the high-charge-density polysaccharide to the proteinase. It is calculated that the acceleration in rate achieved, although lower than that of heparin, approaches that required to be of physiological significance and may be of importance in the anticoagulation role of antithrombin III at sites of high charge density which may occur in vivo.
...
PMID:Effect of a pentosan polysulphate upon thrombin and factor Xa inactivation by antithrombin III. 620 10

The in vivo platelet release reaction in 22 patients with myeloproliferative disorders has been studied by measuring plasma concentrations of the platelet release product beta-thromboglobulin (beta TG). Mean beta TG and mean beta TG: whole blood platelet count ratio were significantly raised in the patient group taken as a whole compared to an age matched control group. No significant increases were observed in the plasma concentrations of thrombin and plasmin sensitive fibrinogen fragments fibrinopeptide A (FpA) and B beta 1-42. The patients were divided into those who had normal, increased or decreased responses to in vitro ADP-induced platelet aggregation. Mean beta TG and the mean beta TG: whole blood platelet count ratio were higher in the increased and decreased responders to ADP than in the normal aggregation group, but the differences in means were not statistically significant. Aspirin given to six patients at a dose sufficient to eliminate the secondary phase of ADP-induced platelet aggregation reduced mean beta TG and the mean beta TG: whole blood platelet count ratio but did not alter mean FpA and B beta 1-42. It is concluded that the enhanced platelet release reaction seen in myeloproliferative disorders is independent of plasma protease activity that arises when coagulation and fibrinolytic systems are activated.
...
PMID:In vivo platelet release in myeloproliferative disorders. 621 39

When the human blood coagulation and fibrinolytic systems are activated thrombin cleaves fibrinopeptide A (FPA) and plasmin cleaves b beta1 leads to 42 from fibrin(ogen). Elevated plasma concentrations of FPA and B beta 1 leads to 42 are evidence for enhanced thrombin and plasma activities in plasma. We have determined the plasma concentrations of FPA and B beta 1 leads to 42 in patients who have had thrombotic stroke. Patients who were studied immediately following stroke were found to have greatly elevated plasma FPA and B beta 1 leads to 42 levels, but these decreased to the concentrations found in an apparently healthy age-matched control group 1 month after the infarct. In contrast, the plasma concentrations of the platelet release product beta-thromboglobulin (beta TG) were slightly, but significantly, elevated immediately following the stroke and these did not alter with time after the infarct. It is concluded that following thrombotic stroke increased thrombin and plasmin activities are to be found in plasma. These increased protease activities are probably not directly associated with an increased in vivo platelet release reaction and may be useful in deciding which patients are at risk of reinfarction or stroke progression.
...
PMID:Activation of coagulation and fibrinolytic systems following stroke. 621 94

The balance between thrombin and plasmin action has been postulated to be an important determinant of thrombosis. Measurement of plasma concentrations of fibrinopeptide A (FPA), which reflect thrombin action on the NH2-terminal end of the A alpha chain, and of B beta 1-42 (thrombin-increasable fibrinopeptide B immunoreactivity-TIFPB) which reflect plasmin action on the NH2-terminal end of the B beta chain have shown systematic changes in the relative concentrations of the two peptides in thrombotic states. This paper reports kinetic data for TIFPB release by plasmin using fibrinogen, fibrin I monomer, and fibrin I polymer as substrates. For fibrinogen and fibrin I monomer the data fit the Michaelis-Menten equation. Experiments were performed with human proteins in 0.15M Tris-buffered saline at pH 7.4 and at 37 degrees C. With fibrinogen as substrate the Km was calculated to be 0.87 microM and the Vmax 3.75 X 10(-5) M/min/unit of plasmin. With fibrin I monomer as the substrate the Km was calculated to be 1.25 microM and the Vmax 5.5 X 10(-5) M/min/unit of plasmin. With fibrin I polymer as substrate the data did not fit the Michaelis-Menten equation but there appeared to be no dramatic differences in rates from those obtained with the other two substrates. The influence of factor XIIIa-induced cross-linking of fibrin was not examined. It is concluded from these findings that fibrinogen and non-cross-linked fibrin I are equally good substrates for plasmin cleavage of the NH2-terminal end of the B beta chain.
...
PMID:The release of B beta 1-42 from fibrinogen and fibrin by plasmin. 622 8

Employing high-performance liquid chromatography (HPLC), we have isolated and quantified the peptides that are released from the NH2-terminus of human fibrinogen B beta-chains by plasmin proteolysis. The peptides were identified by amino acid composition and by a radioimmunoassay developed for fibrinopeptide B detection. B beta 1-42 was the earliest fragment released during limited plasmin proteolysis. The level of this peptide reached a maximum and then began to decline during the course of the digestion. In addition, increasing levels of B beta 1-21 and of FPB followed the production of B beta 1-42. Using purified B beta 1-42 as a substrate, preferential cleavage was shown to occur at the 21-22 bond, with a minor cleavage at the 14-15 bond. Exhaustive digestion yielded two major components which were separated by HPLC: B beta 1-14 (FPB) and beta 22-42. The rate of cleavage at the 14-15 bond, which is the customary site of thrombin proteolysis, was not affected by the addition of hirudin indicating that this was not the result of trace contamination with thrombin. We have also examined plasmin proteolysis at the NH2-terminal region of the B beta-chains of a variety of fibrinogen derivatives and have found similar patterns of B beta 1-42 release. Using HPLC data, we have estimated the Km for plasmic cleavage of the beta 21-22 bond to be 1.8 X 10(-5) M and of the beta 14-15 bond to be 2.8 X 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Sequence of plasmin proteolysis at the NH2-terminus of the b beta-chain of human fibrinogen. 622 62

Serial measurements of the plasma concentration of fibrinopeptide A, thrombin-increasable fibrinopeptide B (reflecting B beta 1-42), desarginyl fibrinopeptide B, beta thromboglobulin, and platelet factor 4 were made before, during, and after delivery in patients with preeclampsia/eclampsia. The data were correlated with routine coagulation studies, hematologic and renal status, as well as with the clinical manifestations. In 11 patients with mild preeclampsia, there were small increases in the fibrinopeptides at the time of delivery, but no other hematologic changes. In 5 patients with severe preeclampsia/eclampsia, there were marked increases in plasma levels of fibrinopeptides and platelet alpha granule proteins, which correlated in time with the clinical manifestations. When the changes in these patients were compared with those occurring in patients undergoing intraamniotic hypertonic saline infusion, it was noted that: (1) patients with severe preeclampsia/eclampsia usually presented when plasmin action on fibrinogen exceeded that of thrombin; (2) in patients with preeclampsia/eclampsia the increase in fibrinopeptides lasted from 3 to 7 days, rather than for several hours as occurred after the infusion of hypertonic saline, indicating a more persistent stimulus to intravascular coagulation in preeclampsia/eclampsia; (3) severe thrombocytopenia and increased platelet protein levels were seen in these patients and were disproportionate to the degree of increase in the fibrinopeptide A level, suggesting that a mechanism other than thrombin must have contributed to the platelet changes; and (4) in two patients with severe preeclampsia/eclampsia, high desarginyl fibrinopeptide B levels preceded renal insufficiency, possibly reflecting fibrin II formation in renal vessels.
...
PMID:Fibrinogen proteolysis and platelet alpha-granule release in preeclampsia/eclampsia. 623 Jan 18

A stable hybridoma secreting homogeneous antibody (immunoglobulin class IgG2a) has been prepared by fusion using cells of immunoglobulin non-secreter myeloma (P3X63Ag8.653) and spleen cells of mice which had previously been immunized with the NH2-terminal CNBr fragment of human fibrinogen, the so-called N-DSK [(A alpha 1-51, B beta 1-118, gamma 1-78)2]. In competitive ELISA or radioimmunoassay this antibody (MAb/1-8C6) cross-reacted with intact fibrinogen, N-DSK, a des fibrinopeptide A (des FPA) variant of N-DSK, the so-called (B)N-DSK, as well as the intact B beta chain (B beta 1-118) obtained from N-DSK. Also, and mot importantly, cross-reactivity was observed with fibrinogen-free ethanol extracts of plasma obtained from patients known to contain high levels of fibrinogen or fibrin degradation products. In vitro thrombin digestion of any of these competitors resulted in complete loss of cross-reactivity. MAb/1-8C6 did not react with the A alpha or gamma-chains of N-DSK, free fibrinopeptide B(FPB), free B beta 15-42, as well as equimolar mixtures of the latter two peptides. These results suggest that MAb/1-8C6 may be to an epitope in or around the thrombin-susceptible B beta 14 Arg-25 Gly bond. Furthermore, due to its reactivity with patient plasma extracts, this antibody may be useful in clinical investigations dealing with fibrino(geno)lysis.
...
PMID:A monoclonal antibody with ability to distinguish between NH2-terminal fragments derived from fibrinogen and fibrin. 665 69

Finback-whale (Balaenoptera physalus L.) heparin was partially digested with a purified heparinase and an octasaccharide with high affinity for antithrombin III was isolated from the digest by gel filtration, followed by affinity chromatography on a column of antithrombin III immobilized on Sepharose 4B. This octasaccharide possessed high inhibitory activity for Factor Xa in the presence of antithrombin III, but was essentially inactive for thrombin-antithrombin III reaction. The anticoagulant activity determined by the activated-partial-thromboplastin-time method was very low (40-70 units/mg), although the initial whale heparin exhibited high activity (252 units/mg). On the basis of the results of chemical analyses, 13C n.m.r. spectrum and enzymic studies with purified heparinase, heparitinases 1 and 2, the predominant structure of the octasaccharide was proposed as follows: delta UA(2S) alpha 1 leads to 4GlcNS alpha 1 leads to 4IdUA alpha 1 leads to 4GlcNAc(6S) alpha 1 leads to 4GlcUA beta 1 leads to 4GlcNS(3S) alpha 1 leads to 4IdUA(2S) alpha 1 leads to 4GlcNS. Comparing this structure with those of the heparin octasaccharides so far reported, the presence of the critical structural elements for binding to antithrombin III was suggested in the pentasaccharide region situated at the reducing end of this octasaccharide. Binding to antithrombin III of the critical structural elements alone would appear to elicit the acceleration of the Factor Xa-antithrombin III reaction. Additional structural elements required for the acceleration of the thrombin-antithrombin III reaction and for the manifestation of high anticoagulant activity are discussed.
...
PMID:Structure and biological activity of finback-whale (Balaenoptera physalus L.) heparin octasaccharide. Chemical, carbon-13 nuclear-magnetic-resonance, enzymic and biological studies. 712 78


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

---