Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coagulation factor XI is a glycoprotein of the contact factor system. Its deficiency is associated with a highly variable bleeding tendency, thus a role in relation to hemostasis appears to exist. However, the importance of factor XI for stimulating intrinsic coagulation in vivo has not yet been determined. To study the procoagulant effects of human factor XIa in vivo, we infused the purified enzyme into normal chimpanzees (100 micrograms) in the absence or presence of the thrombin inhibitor rec-hirudin (1.0 mg/kg loading dose plus 0.3 mg/kg body wt continuous infusion). Factor XIa elicited an immediate activation of factors IX, X, and prothrombin, as measured by their respective activation fragments. However, whereas the activation of factors IX and X was immediate and shortlasting, (peak increments of 6- and 1.4-fold of baseline at 5 minutes after injection), the conversion of prothrombin gradually increased, reaching a summit of 6-fold baseline values after 60 min, and remaining elevated during the course of the experiments. Thrombin-antithrombin complexes also remained elevated during the study period. In the presence of hirudin, the initial activation of factors IX, X, and prothrombin was unchanged, however the further increment in prothrombin fragment F1 + 2 was markedly inhibited. These results demonstrate that factor XIa is a potential agonist of the intrinsic cascade in vivo, which activity is enhanced in the presence of thrombin.
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PMID:Factor XIa induced activation of the intrinsic cascade in vivo. 870 5

The aim of the present work was to study how human umbilical vein smooth muscle cells (HUVSMC) can initiate the coagulation process and to investigate the responses of these cells to thrombin. Exposure of HUVSMC to recalcified human plasma led to a time-dependent production of thrombin, measured both as amidolytic activity and as release of fibrinopeptide A. Thrombin activity was dose-dependently reduced by an anti-human tissue factor antibody (76 +/- 3% at 10 micrograms/ml) and by inhibitors like heparin, rec-hirudin, hirulog 1, Napap and hirunorm, a novel hirudin-like thrombin inhibitor (IC50 = 2 +/- 0.4, 8 +/- 1, 130 +/- 22, 199 +/- 29 and 68 +/- 8 nM, respectively). The release of fibrinopeptide A was similarly prevented (IC50 = 14 +/- 1, 132 +/- 25 and 50 +/- 8 nM for rec-hirudin, Napap and hirunorm, respectively). Exogenously added thrombin increased thymidine incorporation into HUVSMC to 240 +/- 30% of basal (EC50 = 0.49 +/- 0.09 nM) and thrombin inhibitors blocked this effect (IC50 = 10 +/- 3, 37 +/- 17, 343 +/- 165 and 1402 +/- 758 nM for rec-hirudin, hirunorm, Napap and hirulog-1, respectively). Also recalcified human plasma was mitogenic for HUVSMC and its effect was mainly due to endogenously generated thrombin, as shown by the use of thrombin inhibitors. In conclusion, HUVSMC are capable of initiating the extrinsic coagulation cascade, leading to the formation of thrombin which promotes clotting and stimulates DNA synthesis. Thrombin inhibitors prevent both coagulative and cellular effects of thrombin.
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PMID:Human umbilical vein smooth muscle cells as a model to study thrombin generation and function: effect of thrombin inhibitors. 890 3

Recombinant murine MRP14 (mMRP14) was produced in Escherichia coli using the pGEX expression system. The mass of fusion protein, by electrospray ionization-mass spectrometry (ESI/MS), was 39,213 Da which compares well with the theoretical mass (39,210.4 Da). Thrombin digestion of fusion protein was expected at a cloned thrombin consensus sequence (. LVPRGS. ) located between glutathione S-transferase and mMRP14. Analysis of products of digestion by C4 reverse-phase HPLC and SDS-PAGE/Western blotting revealed two immunoreactive cleavage products with molecular weights around 13, 000. Masses of the two proteins determined by ESI/MS were 13,062 and 11,919 Da. The larger product corresponded to the expected mass of recombinant mMRP14 (13,061.9 Da). Analysis of the protein sequence of recombinant mMRP14 revealed a thrombin-like consensus sequence (. NNPRGH. ) located close to the C-terminus. The smaller protein corresponded to a truncated form of rec mMRP14 (rec MRP141-102) with a calculated mass of 11,918.6 Da. Optimization of the cleavage conditions resulted in >95% full-length rec mMRP14. Native mMRP14 contains one intramolecular disulfide bond between Cys79 and Cys90. The full-length recombinant protein was renatured and oxidized in ammonium acetate (pH approximately 7) for 96 h and formed >95% of the native intramolecular disulfide-bonded form. MRP141-102 bound substantially less 65Zn2+ compared to native mMRP14 or rec mMRP14 after transfer to polyvinylidene difluoride and incubation with 65ZnCl2, implicating the His residues located within the C-terminal domain in Zn2+ binding.
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PMID:Overexpression, oxidative refolding, and zinc binding of recombinant forms of the murine S100 protein MRP14 (S100A9). 1004 80

Secondary haemostasis was evaluated in 26 dogs with leishmaniasis and 10 normal dogs by measurements of modified one-stage prothrombin time (m-OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration and fibrin degradation products. There were no significant differences between the groups in the m-OSPT, fibrinogen concentration, or levels of fibrin degradation products. The APTT was significantly (P = 0.006) longer in the infected dogs than in the control group, and in infected dogs with alanine aminotransferase (ALT) activities > 50 U/litre. There was a significant linear regression between ALT and APTT. Thrombin time was significantly (P = 0.003) longer in the infected dogs than in the normal dogs. There were no significant differences between the thrombin times of sick dogs with different levels of creatinine or activities of ALT, or between male and female dogs, whether diseased or normal.
Vet Rec 1999 Feb 13
PMID:Evaluation of secondary haemostasis in canine leishmaniasis. 1009 24

: Utility of coagulation analyzers in real-world settings depends on characteristics that are often not studied comprehensively. This study aimed to investigate the analytical performance, system functionality, practicability, consistency and throughput of two new automated coagulation analyzers in routine laboratory practice. Real-world settings were simulated in three major European hemostasis laboratories and multiple assays were performed in anonymized plasma samples in parallel with routine clinical practice on the cobas t 711 (high-throughput) and cobas t 511 (mid-throughput) analyzers using activated partial thromboplastin time (aPTT), aPTT Lupus, aPTT Screen, Antithrombin (AT), D-Dimer, Fibrinogen, Prothrombin Time (PT)-derived Fibrinogen, PT Owren, PT Rec (recombinant human thromboplastin reagent) and Thrombin Time assays. Precision was tested in a 21-day experiment and accuracy was compared with reference methods of the same laboratory. A number of experiments simulated challenging real-life situations. Pearson's correlation coefficient was more than 0.98 in all assays. Across assays, coefficients of variation ranged from 0.0 to 1.5% for intermediate precision; 0.2 to 3.0% for repeatability and 0.4 to 3.7% for total precision. Good between-run comparability was seen when testing samples under random conditions. Calculated maximum throughput was 197 and 387-402 tests/h for the cobas t 511 and 711 analyzers, respectively. Practicability met or exceeded user expectations in 98% of cases. In a simulated real-life setting of three major laboratories, the new cobas t 511 and cobas t 711 coagulation analyzers demonstrated a good functionality, practicability and performance and the throughput was high.
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PMID:System performance evaluation of the cobas t 711 and cobas t 511 coagulation analyzers in routine laboratory settings. 3282 93