Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New markers of intravascular activation of coagulation have been developed, based on advance in our understanding of the biochemistry of the haemostatic mechanism. These are sensitive methods for measuring of peptides liberated with the generation of thrombin (factor IX activation peptide, factor X activation peptide, peptide F1 + 2), for measuring concentration of enzyme-inhibitor complexes (eg. thrombin-antithrombin III-TAT complexes), as well as for investigating the effect of thrombin on fibrinogen (fibrinopeptide A-FPA) or on protein C (protein C activation peptide). Studies employing these markers indicate that a state of hypercoagulability can be detected in the blood of humans prior to the appearance of thrombotic phenomena. However, further studies will be required to determine whether these methods can identify individuals who are entering a clinically relevant hypercoagulable state as well as to monitor an antithrombotic treatment.
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PMID:[Markers of intravascular activation of coagulation]. 799 71

The purpose of the present study was to determine the normal sequence for the gene encoding factor IX in cats and to characterize the genetic basis for hemophilia B in 2 unrelated male, domestic, mixed-breed cats. Genomic DNA sequence for the entire coding region of the factor IX gene was determined in the affected cats and compared to the sequence obtained from a healthy cat. The factor IX gene in cats encodes a mature protein consisting of 420 amino acids, unlike genes in humans and dogs that encode 415 and 413 amino acid proteins, respectively. Affected cat 1 had a single nucleotide change in exon 8 at the 1st nucleotide position of the codon encoding an arginine (CGA to TGA) at amino acid position 338. This mutation would be predicted to result in the appearance of a premature stop codon in the portion of the gene encoding much of the catalytic domain of the protein. Affected cat 2 had a single nucleotide change in exon 4 at the 2nd nucleotide position of the codon encoding amino acid 82 (TGT to TAT), which would be predicted to result in the substitution of a tyrosine for a cysteine. This substitution would likely result in disruption of a disulfide bond crucial to normal protein structure and function. This study represents the 1st time hemophilia B has been characterized at the molecular level in cats.
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PMID:Characterization of the mutations causing hemophilia B in 2 domestic cats. 1582 64

Therapeutic options for developing countries have to assure an optimum safety and efficacy and low-cost antihaemophilic concentrates. A single blind randomized crossover study was carried out in 12 previously treated HB patients, comparing the pharmacokinetics (PK), thrombogenicity (TG) and safety of two plasma-derived double-inactivated (solvent/detergent heating at 100 degrees C, 30 min) factor IX (FIX) concentrates, UMAN COMPLEX DI (product A) [plasma-derived prothrombin concentrates (PCC)] and a high purity FIX concentrate AIMAFIX DI (product B, HPFIX). In a non-bleeding state, they received one single intravenous dose 50 IU FIX kg(-1) of PCC or HPFIX, and after a wash-out period of 14 days, the other product. We evaluated acute tolerance and determined PK parameters based on FIX levels measured over a 50 h postinfusion period. We studied fibrinogen, platelets, antithrombin, F1 + 2, TAT, D-dimer, over a 360 min postinfusion period. Ten cases remained in on-demand treatment for 6 months, five with PCC and five with HPFIX. PK and anti-FIX inhibitors were repeated at 3 and 6 months. No inhibitors were detected. PK values (PCC vs. HPFIX): clearence (CL; mL h(-1) kg(-1)) 5.2 +/- 1.4 vs. 6.5 +/- 1.4; the volume of distribution at steady state (mL kg(-1)) 154.9 +/- 54.9 vs. 197.5 +/- 72.5; mean residence time (h) 29.7 +/- 8.1 vs. 30.7 +/- 9.2; T(1/2) (h) 22.3 +/- 7 vs. 23.5 +/- 12.3; incremental recovery (IR; U dL(-1) U(-1) kg(-1)) 0.96 +/- 0.17 vs. 0.76 +/- 0.13. HPFIX showed significant lower IR and higher CL. There were no differences in PK at 3 and 6 months. In TG, significant increments in TAT and F1 + 2 at 30 min and 6 h were found with PCC. Product B PK results agrees with reported results for other HPFIX preparations. Use of PCC product A has to consider its thrombogenic activity.
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PMID:Pharmacokinetics, thrombogenicity and safety of a double viral inactivated factor IX concentrate compared with a prothrombin complex concentrate. 1623 7

Coagulation abnormalities are common in severe pneumonia and sepsis, yet little is known about the presence of coagulopathy or its significance in patients with lesser illness severity. We examined coagulation abnormalities in 939 subjects hospitalized with community-acquired pneumonia (CAP) in 28 US hospitals, hypothesizing that abnormalities would increase with illness severity and poor outcomes. We measured plasma coagulation markers (D-dimer, plasminogen activator inhibitor [PAI], antithrombin, factor IX, and thrombin-antithrombin complex [TAT]) at the time of patient presentation to the emergency department and daily during the first wk of hospitalization. Day-1 clinical laboratory test results for international normalized ratio, activated partial thromboplastin time, and platelet count were recorded from the medical record. In our cohort, 32.5% of patients developed severe sepsis and 11.1% died by d 90. Day-1 coagulation abnormalities were common, especially for D-dimer (80.6%) and TAT (36.0%), and increased with illness severity and poor outcomes. However, abnormalities also occurred in those patients who never developed organ dysfunction and differences between groups were modest. The proportion of patients with abnormalities changed over time, yet the magnitude of change was small and not always in the direction of normality. Many patients remaining in the hospital continued to manifest coagulation abnormalities on d 7, especially for D-dimer (86.5%) and TAT (36.9%). In conclusion, coagulation abnormalities were common and persistent in CAP patients, even among the least ill. These findings underscore the complexity of the coagulation response to infection and may offer insights into coagulation-based therapeutics in clinical sepsis trials.
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PMID:Prevalence and significance of coagulation abnormalities in community-acquired pneumonia. 1975 44