Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The report refers to substitution therapy of 33 patients who suffered consumption coagulopathy. Various blood coagulation and fibrinolytic variables were measured. After successful AT III donation to patients suffering DIC, soluble fibrin monomer complexes (SFMC) disappeared within 0.5-12 hours. If AT III decreases SFMC proves positive again. In addition to analysis of AT III we recommend to analyse SFMC to detect thrombin induced consumption reaction (DIC). Furthermore we found the fibrin split product D-dimer was a particularly sensitive indicator of DIC in case of hyperfibrinolysis (D-dimer was analysed in six patients). The reactions of fibronectin and SFMC proved inversely proportional.
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PMID:Fibrin monomer complexes (SFMC) after substitution of antithrombin III (AT III) in consumption coagulopathy. 246 77

Vitronectin is a plasma glycoprotein that has regulatory activity in the complement and the coagulation systems, in cell-cell and cell-substrate interactions, and in monocyte/macrophage function. Because of its potential to participate in several of the processes of inflammation and repair, the association of vitronectin with platelets was investigated. Immunochemical studies demonstrated that the majority of the platelet associated vitronectin was intracellular, while a relatively modest amount was localized to the ectoplasmic portion of the plasma membrane. Analysis by Western blot showed that the electrophoretic mobility of platelet associated vitronectin was indistinguishable from that of vitronectin isolated from plasma. In response to thrombin, approximately 1 microgram of vitronectin was released into the supernate of 10(9) platelets, while somewhat less than one-half of the total platelet vitronectin remained cell associated. The binding of vitronectin to platelets was investigated by comparing the capacity of unlabelled vitronectin and fibronectin to inhibit binding of radiolabelled fibronectin to thrombin stimulated platelets. On a weight basis, inhibition by the two proteins was equivalent, suggesting that vitronectin competes with fibronectin for binding to platelet glycoprotein IIb/IIIa. These results demonstrate that vitronectin is a platelet specific protein which, because of its multifunctional properties, may participate in physiological and pathophysiological events associated with thrombosis and haemostasis.
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PMID:Vitronectin (S protein) is associated with platelets. 246 74

Guanidinobenzoatase is a proteolytic enzyme capable of degrading fibronectin and is a tumour associated enzyme. Guanidinobenzoatase has been shown to be an arginine selective protease and is distinct from trypsin, plasmin and thrombin, the latter enzymes can be assayed with bis(carbobenzyloxycarbonyl-L-argininamido)-Rhodamine or BZAR. Guanidinobenzoatase is inhibited by BZAR when the enzyme is assayed in free solution and when the enzyme is cell-bound in frozen sections of tumour containing tissues. It is proposed that BZAR and its analogues may be of value in inhibiting tumour cell invasion in vivo and also that the selectivity of BZAR may be used to direct cytotoxic drugs to tumour cells possessing active guanidinobenzoatase.
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PMID:Inhibition of guanidinobenzoatase by a substrate for trypsin-like enzymes. 246 71

The role of glycoprotein IV (GPIV) in platelet activation processes has been examined by several different approaches: (i) Fab fragments of a monospecific polyclonal antibody to purified platelet GPIV (approximately 20 micrograms/ml) completely inhibited platelet shape change, aggregation, and secretion induced by collagen. Aggregation and secretion by ADP (but not shape change) and by epinephrine were also inhibited, but there was no effect on platelet activation induced by thrombin, arachidonate, or ionophore A23187. (ii) Purified GPIV was able to compete completely with membrane-bound GPIV to inhibit platelet activation induced by collagen, including shape change, but not in activation induced by any of the other platelet agonists. 50% inhibition of collagen-induced activation and secretion were obtained at GPIV concentrations of approximately 10 nM (1 micrograms/ml). (iii) Purified GPIV bound rapidly and reversibly to collagen Type I fibrils, and binding was not inhibited by adhesive proteins such as denatured collagen, fibronectin, fibrinogen, or von Willebrand factor. The direct binding of purified GPIV to collagen Type I fibrils fit best to a single site model with Kd 0.34 +/- 0.10 nM. (iv) Using a microtiter assay, platelet adhesion to collagen was shown to be inhibited by Fab fragments of monospecific polyclonal anti-GPIV antibodies, but adhesion to other adhesive proteins was unaffected. (v) When anti-GPIV was added at various times during adhesion the time dependence of inhibition was seen to be biphasic. Anti-GP antibody was able to reverse adhesion that occurred within the first 5-8 min and to inhibit adhesion occurring thereafter. These results demonstrate that GPIV mediates the early stages of platelet recognition by and attachment to collagen but that there may be a second GPIV-independent mechanism that mediates the subsequent anchorage of these adherent platelets.
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PMID:Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. 246 70

Although the fibrin adhesion enjoys increasing success in many areas of surgery, it has not, however, become fully established in nerve anastomosis. It was in this area particularly that significant advantages were expected. As the fibrin clot dissolved prematurely, however, and dehiscences ensued, antifibrinolytic substances had to be added to the adhesive. Fibroses occurred frequently as a result, which to date encumber nerve adhesive. We examined various factors of the adhesive system for their fibrosis-inducing effect. We were able to establish that no additional fibrosis-promoting effect emanated from aprotinin and the fibrin clot as a supply barrier, whereas thrombin, Factor XIII and fibronectin possess a fibrosis-promoting effect.
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PMID:Problems of fibrin adhesion of the nerves. 247 44

The generation of trace amounts of thrombin at artificial surfaces in contact with blood is likely to be a contributing factor in thrombosis on biomaterials. Using an in vitro capillary perfusion system, platelet accumulation on glass surfaces, uncoated or precoated with purified bovine collagen or human plasma proteins, was determined in the presence or absence of preadsorbed purified human thrombin. Static adsorption for 15 min at 22 degrees C from solutions of thrombin 100 NIH units (33 micrograms)/ml gave surface concentrations in the range 0.019-0.101 micrograms/cm2. Protein coated capillaries, thrombin treated or untreated, were perfused for 2 min at 37 degrees C with suspensions of washed 111In-labeled human platelets in Tyrode's-albumin buffer containing 40% washed red blood cells, under conditions of controlled, non pulsatile laminar flow (50 s-1 or 2,000 s-1). Platelet accumulation was increased in the presence of surface adsorbed thrombin on uncoated and albumin or fibrinogen coated glass but little affected on fibronectin or collagen coated glass. On von Willebrand factor (vWF) coated glass, thrombin enhancement was observed only at high shear forces. In experiments using antibodies against human platelet alpha-granule proteins, thrombin stimulated platelet deposition in uncoated glass capillaries was inhibited at 2,000 s-1 by anti-vWF and to a lesser extent by anti-fibrinogen but not by anti-thrombospondin antibodies.
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PMID:Thrombin stimulated platelet accumulation on protein coated glass capillaries: role of adhesive platelet alpha-granule proteins. 248 Jun 55

The fibrinous adhesion, although generally adopted and more and more successfully applied in many sectors of surgery, is not yet fully established in the anastomosis of separated nerves. Initially, the adhesion was expected to offer some essential advantages in this domain, especially in the prevention of suture granulomas. However, the blood clots dissolved too early, and this resulted in the formation of dehiscences. So antifibrinolytic substances had to be added to the adhesive, and this led to a frequent appearance of fibroses. The adhesion of nerves is still hampered by this fact. Now we have examined the fibrosis-inducing effect of different factors of the adhesive system. We found that aprotinin and the fibrin clot as an obstacle to supply had no additional fibrotic effect, whereas thrombin, factor XIII and fibronectin promoted the formation of fibroses.
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PMID:[The effect of fibrin gluing and its important components on fibrosis of nerve anastomoses]. 248 67

Platelets hyperaggregability and hypersecretion fibronectin (Fn) are known to occur in peripheral vascular disease (PVD) and diabetes mellitus (DM) with microangiopathy. To determine whether an increase in platelet membrane bound Fn constitutes to hyperaggregability of platelets, washed platelets from normal subjects and from patients with peripheral vascular disease and patients with diabetes mellitus were examined for the presence of fibronectin (Fn) by means of fluorescein linked antibody to Fn. Platelets from peripheral vascular disease and diabetes mellitus patients tended to aggregate during preparation and apparently exhibited greater fluorescence in platelet "smears" than was observed in smears from controls. In contrast, when washed platelet "smears" were prepared from platelet preparations containing iloprost, an analogue of prostacyclin, platelet aggregates did not form and the 'excess' of fluorescence disappeared from all the three groups. When platelets were stained for Fn fluorescence in suspensions, no fluorescence was observed on the surface of platelets from peripheral vascular disease and diabetes mellitus patients or controls. On stimulation with thrombin washed platelet suspension showed fluorescence for Fn. Platelet activation leads to Fn appearing on platelet surface but this effect cannot be quantified by optical fluorescence microscopy.
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PMID:A study of platelet fibronectin immunofluorescence in peripheral vascular disease and diabetes mellitus. 248 53

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.
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PMID:Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S. 252 Dec 76

We investigated the effect of agents which raise intracellular levels of cyclic AMP (cAMP) on the secretion of tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) by cultured human umbilical-vein endothelial cells. Significant inhibition of baseline (unstimulated) t-PA and PAI-1 secretion was observed in response to several agents which, when added exogenously, cause increased intracellular cAMP: cholera toxin, 1-methyl-3-isobutylxanthine (MIX), dibutyryl-cAMP, and prostaglandin E1. These agents also significantly reduced or abolished the previously reported stimulatory effects of thrombin and histamine on t-PA secretion, and, with the exception of MIX, significantly reduced the previously reported stimulatory effect of thrombin on PAI-1 secretion. MIX at a concentration (10 microM) below that required to inhibit t-PA and PAI-1 secretion when tested alone, significantly increased the inhibitory effects of cholera toxin, dibutyryl-cAMP, and prostaglandin E1 on both t-PA and PAI-1 secretion. The data suggest that elevated intracellular levels of cAMP inhibit both spontaneous endothelial secretion of t-PA and PAI-1, and secretion induced by agents (thrombin and histamine) which stimulate endothelial phosphoinositide metabolism, consistent with bidirectional regulation of endothelial fibrinolytic protein secretion by the adenylate cyclase and phosphoinositide signal transduction pathways. The inhibitory effects of cAMP do not appear to be specific for t-PA and PAI-1, since cholera toxin and MIX also inhibited endothelial secretion of the adhesive protein, fibronectin. Significant inhibition of baseline endothelial t-PA and PAI-1 secretion was also caused by the stable prostacyclin analogue iloprost (ZK 36 374) and by arachidonic acid, which is converted by endothelial cells to prostacyclin, suggesting that prostacyclin produced endogenously by endothelial cells may inhibit secretion of fibrinolytic proteins by increasing intracellular cAMP.
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PMID:Inhibition of endothelial secretion of tissue-type plasminogen activator and its rapid inhibitor by agents which increase intracellular cyclic AMP. 254 66


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