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)

Heparin was covalently bound to solid substrate surfaces by means of four different chemistries. It was coupled to polymethylacrylate (PMA) beads with glutaraldehyde, carbodiimide, or radical polymerization initiated by Ce4+, or to agarose beads with cyanogen bromide. Each of these chemistries produced measurable amounts of surface-bound heparin, which was minimally elutable in contact with plasma. Antithrombin (AT) binding by heparinized PMA materials (compared with PMA control beads) ranged from no AT binding for the material heparinized with carbodiimide (PMA-Alb-Hep(EDC] to 3.6 micrograms/ml packed beads for the material heparinized by radical polymerization (PMA-MA-Hep). Heparin-like catalytic activity of these materials (assayed by measuring the generation of thrombin-antithrombin complex in plasma) correlated well with the amount of heparin bound, but not as well with AT binding capacity. Heparinized agarose, which exhibited a large AT binding capacity (2.2 mg AT per milliliter of packed gel), had virtually no catalytic activity because of its inability to release thrombin-antithrombin complex from the surface. Platelet interaction with heparinized materials that exhibit high AT binding capacity was reduced by pretreatment with normal plasma but not by pretreatment with AT-depleted plasma. Platelet interaction with heparinized materials with low AT binding capacities was not reduced by pretreatment with normal plasma. We conclude that AT binding by heparin reduces the platelet reactivity of heparinized surfaces.
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PMID:Catalytic activity and platelet reactivity of heparin covalently bonded to surfaces. 397 61

The unique finding of normal proalbumin in human plasma provides an insight into the mechanism of propeptide cleavage. Proalbumin, present as 1-5% of the total albumin, was found in a boy whose prime problem was the presence of a mutant proteinase inhibitor, alpha 1-antitrypsin Pittsburgh (358 Met----Arg) [2]. The inferred structure of human proalbumin was confirmed as Arg-Gly-Val-Phe-Arg-Arg-Alb. On incubation with various enzymes (trypsin, tryptase, thrombin, chymotrypsin, chymase and cathepsin B), only trypsin was capable of converting proalbumin to albumin. There was no conversion when proalbumin was incubated with whole blood, plasma or serum. However, intravenous injection of proalbumin into a rat resulted in complete conversion to albumin, the half-life of this process being 6 h. We conclude that propeptide cleavage is dependent on a serine proteinase which is inhibited intracellularly, by the mutant inhibitor, and that all the albumin in the boy was secreted as proalbumin, but was subjected to a separate cleavage process after export from the hepatocyte.
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PMID:Circulating proalbumin associated with a variant proteinase inhibitor. 633 53

The anticoagulant activity of albumin-heparin conjugates covalently immobilized on carboxylated polystyrene beads was determined before and after exposure to different plasma/PBS dilutions using a thrombin inhibition assay, a FXa inhibition assay, and a modified aPTT assay. Exposure of albumin-heparin modified surfaces (alb-hep surfaces) to plasma dilutions resulted in surfaces with a lower anticoagulant activity than surfaces which were not exposed to plasma dilutions. The reduction of the activity increased up to +/- 80% when the surfaces were exposed to solutions containing more than 70% plasma. Alb-hep surfaces incubated in plasma which was preexposed to heparin-Sepharose retained 30% of their initial activity. These observations were attributed to non-specific adsorption of plasma proteins onto the surface and to interaction of heparin binding proteins with the immobilized heparin. Both processes result in a decreased accessibility of the immobilized heparin and thus in a reduced anticoagulant activity displayed by the heparinized surface. Identification of adsorbed proteins with SDS gel electrophoresis and immunoblotting revealed that many different proteins were present at the heparinized surface. Only small differences were observed between the gel electrophoresis pattern of adsorbed proteins obtained from heparinized surfaces and from a surface containing immobilized albumin.
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PMID:The effect of protein adsorption on the anticoagulant activity of surface immobilized heparin. 863 81

In spite of the fact that prothrombin is produced by cells within the central nervous system, its presence in the cerebrospinal fluid (CSF) has not been investigated. We determined the concentration of prothrombin in CSF with reference to the concentration in plasma in paired samples from 18 "normal" control patients and 4 patients with relapsing-remitting type of multiple sclerosis (MS). The newly developed ELISA was very specific (no cross-reactivity with thrombin) and sensitive (detection limit--0.7 ng/ml) with an imprecision of CV = 8.3% (intraseries) and 7.0% (interassay). The mean prothrombin concentration in normal CSF was 0.55 mg/l (CV +/- 33%, range: 0.28-0.93 mg/l), in normal plasma 121.8 mg/l +/- 21%, resulting in a mean CSF/plasma concentration quotient (Q(Proth)--4.5 x 10(-3) (CV +/- 35%, range: 2.1-8.3 x 10(-3)) corresponding to a mean albumin quotient in this group of subjects of Q(Alb) = 5.8 x 10(-3). Due to the Q(Proth) and the molecular weight of prothrombin (72 kDa)--similar to that of albumin--we conclude that prothrombin in normal human CSF originates predominantly (>95%) from blood. The enzymatic activity in CSF is conserved. Comparable results obtained in MS patients with only few small MRI lesions suggest that local chronic inflammatory disease of the central nervous system does not influence prothrombin concentration in the CSF if the blood-CSF barrier function is normal.
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PMID:Prothrombin in normal human cerebrospinal fluid originates from the blood. 970 91

Endothelial cell (EC) seeding significantly improves the blood compatibility of artificial surfaces. Although a coating consisting of albumin and heparin (alb-hep) is a suitable substrate for seeded ECs, binding of ECs to the substrate further improves when small amounts of fibronectin are present in the alb-hep coating. Alb-hep conjugate was immobilized on carbon dioxide gas plasma-treated polystyrene (PS-CO(2)), thereby significantly increasing the recalcification time of blood plasma exposed to this surface. Furthermore, surface-immobilized alb-hep conjugate inhibited exogenous thrombin. Heparin activity was reduced by adding fibronectin on top of a monolayer of alb-hep conjugate, but not by simultaneous coating of fibronectin and alb-hep conjugate. Coating of PS-CO(2) with alb-hep conjugate significantly decreased contact activation (FXII activation). The number of platelets deposited from blood plasma on PS-CO(2) coated with alb-hep conjugate was twice as high as on PS-CO(2) coated with albumin. Addition of fibronectin to alb-hep conjugate-coated PS-CO(2) had no significant effect on the number of adhered platelets. Seeding of the substrates with ECs significantly reduced the number of adhered platelets under stationary conditions. Platelets deposited onto endothelialized surfaces were primarily found on endothelial cell edges, and sparingly on areas between ECs. In conclusion, alb-hep conjugate-coated surfaces display anticoagulant activity. ECs adhering to and proliferating on this coating significantly decrease the number of platelets which adhere to the surface. Therefore, alb-hep conjugate-coated surfaces form a suitable substrate for seeding of ECs in low density. Although application of fibronectin on top of the coating decreases the anticoagulant activity to some extent, it might be useful in view of the improved adherence of ECs to the coating.
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PMID:Blood compatibility of surfaces with immobilized albumin-heparin conjugate and effect of endothelial cell seeding on platelet adhesion. 1048 78

The blood hemostatic activity of the Tibetan medicinal herb Lamiophlomis rotata was evaluated in BALB/c mice and Wistar rats. L. rotata aqueous extract (LRAE) was given to mice at concentrations of 0.5, 1.0, 2.0 g/kg body weight and 0.75, 1.5, 3.0 g/kg to rats. The hemostatic activity of LRAE was estimated by changes in bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). At the same time hepatic function and blood fat indexes including AST, ALT, Alb, Chol and LDL-C were measured also. The results showed that an appropriate level of LRAE could shorten the BT and TT values and increase the Alb level paralleling that of FIB. However, the shortening of the PT was only possible by a high and long administration of LRAE, and no change in APTT was observed. On the other hand, LRAE showed some effects in improving the liver function and reducing blood lipids by decreasing the levels of AST, ALT, Chol and LDL-C. All these changes had a significant dose-effect and time-effect relationship. These results confirm the hemostatic and thromboplastic effects of L. rotata and these effects might be implemented by improving the synthetic function of the liver.
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PMID:Experimental study on the hemostatic activity of the Tibetan medicinal herb Lamiophlomis rotata. 1844 44

This study was aimed to investigate the correlation of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB), antithrombinIII (ATIII), D-dimer (D-D) levels] with inflammatory markers [procalcitonin (PCT), C reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)] for sepsis in hematologic malignancy patients. A total of 326 febrile in patients with hematologic diseases from 2062 patients in West China Hospital, Sichuan University from March 2011 to April 2013 were retrospectively analyzed. The patients were divided into sepsis group(n = 72), non-sepsis group(n = 176) and non-sepsis with low Alb group (n = 78) according to blood culture. The results showed that the values of PT, APTT, D-dimer, Plt in sepsis group were higher than those in non-sepsis group, and the difference between them was statistically significant. While the ATIII level in the sepsis group was lower than that in non-sepsis group, and the difference between them was statistically significant (P < 0.05). And the four inflammatory biomarkers in the sepsis patients were higher than those in non-sepsis patients (P < 0.05). TT and FIB level were not significantly different (P > 0.05). There was not a significant difference in these indicators between non-sepsis group and non-sepsis with low Alb group. The correlation analysis suggested that the level of PCT positively correlated with APTT, D-dimer level (P < 0.05); and negatively correlated with the ATIII (P < 0.05). It is concluded that sepsis results in the concurrent activation of inflammatory and procoagulant pathways. The hematologic malignancy patients with sepsis have an obviously higher systemic inflammatory response, and accompanied with coagulation dysfunction.
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PMID:[Correlation of coagulation indicators with inflammatory markers for sepsis in the patients with hematological malignancies]. 2533 93