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

Amidolytic chromogenic substrate assays are frequently used to determine the anticoagulant activities of various commercial heparins. With the help of a combined assay method heparin characterization is made possible using the TAT/XAT quotient under consideration of the simultaneous inhibition of the two serine proteases thrombin and factor Xa by antithrombin III. The test is primarily designed for qualitative characterization where a numerical value can be assigned to every heparin. However, quantitative aspects may also be evaluated.
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PMID:Evaluation of an amidolytic test for comparative calibration of HMW- and LMW-heparins. 166 65

In order to assess the thrombin and plasmin generation in vivo in disseminated intravascular coagulation (DIC), plasma levels of thrombin-antithrombin III (ATIII) complex (TAT) and plasmin-alpha 2-antiplasmin (a2AP) complex (PAP) were measured together with standard coagulation and fibrinolytic parameters in 80 patients with DIC. Both TAT and PAP were markedly elevated in patients with DIC. When plotted by the underlying disease categories, differences in the magnitude of the elevations of these complexes were recognized among groups. Patients with acute promyelocytic leukemia (APL) had the highest PAP, the lowest TAT/PAP ratio, low a2AP, and low fibrinogen, indicating that the most excessive fibrinolysis can occur in APL. Similar profiles, although less marked, were observed in patients with other leukemias and vascular diseases. Patients with sepsis showed the highest TAT/PAP ratio and the lowest PAP with no decrease in a2AP or fibrinogen, demonstrating a relatively impaired fibrinolysis. Patients with cancer had a relatively high TAT and high TAT/PAP ratio. In addition, both TAT and PAP were markedly elevated in patients with shock. From these, it was suggested that, although laboratory manifestations in DIC are extremely variable from patient to patient, underlying disorders are, at least in part, responsible for the observed variations. Recognition of this variable activation of coagulation and fibrinolysis would be helpful for the proper management of patients with DIC.
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PMID:Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders. 200 32

Activation of human normal serum with tetanus/antitetanus immune complexes (TAT-IC) resulted in increased binding of 125I-labeled interleukin-1 beta (IL-1 beta) to serum factors, as opposed to untreated serum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by autoradiography showed labeling of two large molecular mass factors of an apparent molecular weight (Mr) of 200,000 and 400,000, respectively. These complexes could be dissociated by reduction. No complexes were formed when reducing compounds were added to serum-TAT-IC-125I-IL-1 beta mixtures. Complex formation was largely prevented by alkylating compounds. Molecular sieve chromatography of TAT-IC-activated serum confirmed that 125I-IL-1 beta became bound to high Mr serum proteins. Fractions containing high molecular 125I-IL-1 serum protein complexes partially retained IL-1-like activity since they induced proliferation of an IL-1-dependent murine T helper (D10G4) cell lineage. The 125I-IL-1 beta binding factors could be immunoprecipitated from TAT-IC-activated serum 125I-IL-1 beta solutions by antisera to alpha 2-macroglobulin (alpha 2M) or to the third complement component (C3). SDS-PAGE of the immunoprecipitates showed radioactive bands corresponding to the expected Mr resulting from complex formation between 125I-IL-1 beta and these two proteins. Treatment of purified plasma alpha 2M and C3 with trypsin or activation with methylamine, which causes cleavage of the internal thiol ester and the appearance of free thiol groups in these proteins, mediated binding of 125I-IL-1 beta to alpha 2M and C3b. The results suggest that cleavage of the internal thiol ester in C3 and alpha 2M makes these plasma proteins susceptible to binding of 125I-IL-1 beta and that free thiol groups do play a role in the formation of 125I-IL-1 beta plasma protein complexes. Activated C3 and alpha 2M may function as IL-1 beta carrier proteins in biologic fluids, in addition to their other physiologic roles.
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PMID:Binding of recombinant interleukin-1 beta to the third complement component and alpha 2-macroglobulin after activation of serum by immune complexes. 169 30

Routine postoperative monitoring of plasma coagulation and fibrinolysis system values after cesarean delivery in 191 women who did not develop thrombosis and 16 who did revealed a preoperative defect in the fibrinolysis (PAI, TAT) and inhibitor (AT III) systems. Significant postoperative correlations in the drop in antithrombin levels could not be explained solely by hemodilution. Moreover, a disturbance of the equilibrium of the alpha-2 increase and plasminogen was observed, favouring alpha-2 antiplasmin. Hydroxyethyl starch is capable of simultaneously influencing hypercoagulability and postoperative status. The only difference noted between the two groups of drugs was in the course of the PAI concentration (P less than 0.02). It would therefore appear logical in clinical practice to extend preoperative tests to include determination of the plasminogen activator inhibitor and the thrombin-antithrombin complex.
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PMID:[Changes in plasma coagulation and fibrinolysis following cesarean section and relationship to deep venous thrombosis. Results of a randomized prospective comparative study with 6% hydroxyethyl starch 0.62 and low-dose heparin as thrombosis prophylaxis]. 171 8

The present study was undertaken to determine whether the extent of Factor VII elevation correlated with the severity of coronary artery disease and whether zymogen or activated Factor VII was responsible for this elevation. A group of 69 patients with coronary artery disease with old myocardial infarction was compared with 28 control subjects. The patient groups showed elevated levels of Factor VII procoagulant activity (FVII:C) and more markedly elevated Factor VII antigen (FVII:Ag) levels than the control group; therefore they had a decreased FVII:C to FVII:Ag ratio. The increased Factor VII level in the patient groups was caused by elevated Factor VII zymogen levels, and not by activated Factor VII. Since FVII:C levels strongly correlated with the titer of thrombin-antithrombin III complexes in all patients, the hypercoagulable state accompanying severe coronary atherosclerosis seems to underlie the increase of FVII and TAT in the stable phase of myocardial infarction.
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PMID:Elevation of factor VII activity and mass in coronary artery disease of varying severity. 174 7

The pattern of arterial supply to the various parts (clavicular, sternocostal and aponeurotic) of the pectoralis major muscle was studied in 7 cadaver dissections and 10 angiograms by injecting a radio-opaque substance. Three main arteries supplied the muscle, i.e. the pectoral branch of the thoracoacromial trunk (TAT-PB), the lateral thoracic artery and the perorating branch of the internal thoracic artery, supported by other branches of the TAT and the superior thoracic artery. It is observed that the TAT-PB, a chief vascular pedicle, anastomoses freely with other arteries and supplies most parts of the muscle. The present study is mainly focussed on the exclusion of the chief vascular pedicle of muscle to eliminate the confusion of previous studies and prevent the unnecessary hindrance and complications of the muscle flap.
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PMID:Anatomical basis for the clinical application of the arterial supply of musculus pectoralis major. 174 31

Several laboratory methods are available to measure r-hirudin, including clot-based, amidolytic, immunologic, and physicochemical techniques. The global tests, such as the PT, APTT, and Heptest, did not show an adequate response to r-hirudin in the range of 0.5 to 10.0 micrograms/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis. The 10 U/ml thrombin time assay was very sensitive to r-hirudin, whereas the 10 U/ml calcium thrombin time gave a dose-dependent response from 0.15 to 10.0 micrograms/ml. Whole blood clotting assays (ACT, TEG) effectively measured r-hirudin levels up to 25 micrograms/ml. The amidolytic anti-Factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective, particularly when modified to decrease the sample: thrombin ratio for higher r-hirudin concentrations. This assay may be useful in quality control, since it is biochemically defined and reagents are easily standardized. Thrombin generation assays based on synthetic substrates showed limited effect of r-hirudin; however, assays based on TAT complex and prothrombin fragment F1+2 generation showed a dose-dependent response. Immunologic methods (ELISA) are under development. Since these assays measure both complexed and noncomplexed hirudin, and since they are only sensitive to submicrogram levels, they may only be useful for the direct quantitation of absolute levels of r-hirudin but not for monitoring clinical anticoagulation. Thus, thrombin-based clotting, amidolytic, and immunologic assays can be used to evaluate and measure r-hirudin. However, optimization of each assay to respond to high and low concentrations of r-hirudin and their application to clinical monitoring, batch control, and standardization needs to be determined.
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PMID:Comparative studies on various assays for the laboratory evaluation of r-hirudin. 177 8

alpha-Anomeric oligonucleotides are resistant to nucleases and display parallel hybridization with complementary DNA and RNA sequences. Although alpha-DNA/beta-RNA duplexes are not substrates for RNases H, alpha-oligos are able to inhibit translation through a RNase H independent mechanism. alpha-Oligos and their alpha-phosphorothioate analogs (12 mer) targeted against the splice acceptor site of the HIV-TAT gene were potent inhibitors of de novo HIV infection. Furthermore alpha-phosphorothioate and dithioate homo-oligomers exhibit an in vitro, nonsequence-specific, inhibitory effect on HIV reverse transcriptase.
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PMID:Alpha-oligonucleotides: a unique class of modified chimeric nucleic acids. 177 67

In liver disorders alterations of the coagulation system are mainly due to a reduced synthesis of coagulation proteins. In addition, an enhanced intravascular consumption of coagulation factors is discussed controversely in liver diseases. By measuring factor IXiAT- and TAT-complexes we tried to find out, whether coagulation activation in liver patients leads to activation of the complete coagulation cascade followed by DIC or whether in some diseases a futile partial coagulation activation develops. In all liver diseases examined, elevated factor IXiAT-complexes were demonstrated, while TAT-complexes were only elevated in chronic active hepatitis, metabolic decompensated liver cirrhosis and in patients suffering from end stage liver disease. We conclude that all liver diseases examined lead to an activation of the coagulation cascade. A complete activation followed by DIC only occurs in patients with very severe liver disorders.
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PMID:Coagulation activation in liver diseases. 181 43

Human immunodeficiency virus type 2 (HIV-2) gene expression is downmodulated by sequence elements downstream of the transcriptional initiation site, corresponding to the U5 region of the long terminal repeat (LTR) and further downstream. This repression appeared to be related more to the length of the sequence intervening the transcriptional initiation site and the coding region than to a particular sequence content. The repressive effect of the downstream segment was not affected by HIV-2 and HIV-1 TAT or by the cytomegalovirus transactivator IE-2 gene. Nor was it affected by T-cell activation signals or by such cytokines as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interferon-gamma (IFN gamma), and interferon-alpha (IFN alpha). In contrast to HIV-1, HIV-2 LTR-directed gene expression was not modulated by TNF-alpha. A specific sequence element, located downstream of the TAR element in the R region, seemed to participate in modulation of gene expression. This element interacted with a nuclear protein with a mobility of about 26 kD. The repressive effect of the downstream sequence was to a certain extent cell type dependent, suggesting the involvement of cell type-specific factors. It was more effective in human lymphocytic CEM cells than in Jurkat cells. This may be relevant to the HIV-2 cell tropism (replication), latency, and virulence.
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PMID:Human immunodeficiency virus type 2 (HIV-2) gene expression: downmodulation by sequence elements downstream of the transcriptional initiation site. 181 41


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