Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An ability of intravenous nitroglycerin to interfere with the anticoagulant properties of intravenous heparin would have profound clinical implications. To investigation nitroglycerin-heparin interactions, the following pilot study was performed. Patients (N = 18) admitted to the coronary care unit with a diagnosis of either acute myocardial infarction or unstable angina were divided into four treatment groups: (1) intravenous nitroglycerin and intravenous heparin; (2) intravenous nitroglycerin alone; (3) intravenous heparin alone; or (4) neither intravenous nitroglycerin nor intravenous heparin. Serial determinations of activated partial thromboplastin time (APTT), serum heparin concentration, antithrombin III (ATIII) antigen (ATA), and ATIII activity (ATC) were obtained over a 72-hour period. Overall, patients receiving intravenous nitroglycerin did not differ significantly from other patients in APTT, heparin dose, heparin concentration, ATA, ATC, or ATA/ATC ratio (ATR). However, patients receiving intravenous nitroglycerin at a rate exceeding 350 micrograms per minute had a lower APTT (p less than 0.05), lower ATC (p = 0.02), higher ATR (p = 0.004), and a larger heparin dose requirement than patients receiving lower infusion rates. ATR correlated directly (r = 0.91; p less than 0.05) and ATC inversely (r = -0.78; p less than 0.05) with the intravenous nitroglycerin dose. Serum heparin concentration did not correlate with the intravenous nitroglycerin dose. Intravenous nitroglycerin-induced heparin resistance occurs at a critical nitroglycerin dose. A nitroglycerin-induced qualitative ATIII abnormality may be the underlying mechanism.
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PMID:Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin III abnormality. 190 82

DNA sequence analysis of the gene coding for the variant protein, factor IXLong Beach (FIXLB), has identified a transition mutation in an otherwise normal factor IX (FIX) gene. Genomic DNA clones spanning 35 kilobase (kb) pairs of the FIXLB gene were isolated. A gene analysis strategy that specifically characterized exons and their flanking intron sequences predicted the entire amino acid sequence of FIXLB. A thymine to cytosine transition causes the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon VIII of the FIXLB gene. This mutation results in an amino acid substitution at residue 397 of the FIX zymogen and the phenotypic display of hemophilia-B. Previous studies revealed that activated purified FIXLB (FIXaLB) had normal Ca2+, phospholipid, and factor VIIIa binding characteristics. However, FIXaLB activated factor X or factor VII (with their cofactors Ca2+ and phospholipid) at significantly reduced rates, suggesting that the defect in FIXaLB lies near or within the catalytic triad of the FIX heavy chain. Identification of an amino acid substitution near the carboxy-terminus of the FIXaLB heavy chain supports the earlier characterization of this variant protein. Moreover, our data identify a residue in the catalytic domain of FIXa essential for normal function.
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PMID:Genetic defect responsible for the dysfunctional protein: factor IXLong Beach. 340 2

Fucosylated glycosaminoglycan (FG) is a structurally novel glycosaminoglycan derivative, and it has potent anticoagulant activity. Depolymerized FG (dFG) is a selective factor Xase (FXase, FIXa-FVIIIa complex) inhibitor and it has antithrombotic action without major bleeding risks. In this study, we report the effects of dFG-3 (Mw ~14kDa) on the catalysis rates of factor IIa (FIIa), factor Xa (FXa) and factor IXa (FIXa) inhibition by antithrombin (AT), and the kinetic of the interactions between coagulation proteases or inhibitors and dFG-3 were also studied using biolayer interferometry (BLI) technology. We found that dFG-3 had much weaker catalysis activity of coagulation proteases inhibition by AT compared with heparin (UFH). The binding affinity of AT bound to dFG-3 was lower than UFH, and the UFH-AT interaction fitted well with biphasic-binding model while dFG-3-AT interaction was monophasic-binding, suggesting dFG-3 might not have allosteric activation effect on AT. The results are consistent with AT-independent inhibitory activities of dFG-3. dFG-3 could strongly bind to FIXa with much higher affinity than UFH, further explained the reason for its potent FXase inhibitory activity. Additionally, the binding ability of dFG-3 and FIXa decreased with decreasing molecular, and the fucose side chains and carboxyl groups of dFG-3 might be required for its high affinity binding with FIXa. Our data supports further the investigation of dFG-3 as a promising anticoagulant drug inhibiting the intrinsic FXase by binding to FIXa.
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PMID:Interactions between depolymerized fucosylated glycosaminoglycan and coagulation proteases or inhibitors. 2761 97

This study assessed the global hemostasis (including prothrombin time [PT], activated partial thromboplastin time [aPTT], antithrombin activity [ATA], fibrinogen and d-Dimer concentrations, platelet count, plateletcrit and thromboelastometry) in healthy pregnant bitches, comparing the results with those of healthy bitches at different estrous cycle stages, and assessed whether hemostatic changes during pregnancy are associated with serum progesterone concentration or the presence of fetuses in utero. The results show that pregnant bitches have higher fibrinogen concentration, platelet count and platelatecrit, and that fibrin and global clot formations occur faster than in non-pregnant bitches at different estrous cycle stages. Additionally, clot strength was higher in pregnant bitches than in non-pregnant ones. There were no differences in PT, ATA, and D-dimer concentration between all study groups. The aPTT was significantly shorter in bitches at the fourth and last pregnancy weeks, compared to the anestrus group, and shorter in both the fourth and last pregnancy weeks groups, compared to diestrus group. These results all support a hypercoagulable state in healthy pregnant bitches, unassociated with progesterone concentration.
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PMID:Global hemostasis in healthy bitches during pregnancy and at different estrous cycle stages: Evaluation of routine hemostatic tests and thromboelastometry. 2858 9