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)

Thromboembolism and infection remain potential threats for long-term circulatory assist and replacement devices. The alteration of the hemostatic system and of blood cell functions caused by device implantation may predispose the recipient to these complications. Many sensitive coagulation assays and the technology of flow cytometry would be powerful tools for this investigation. The availability of such immunologic technologies for animal species other than humans has yet to be established. In a series of in vitro tests we found that the following assays, among others, are usable in calves: TAT, TxB2, platelet surface glycoprotein IIbIIIa, and membrane aminophospholipid. F1.2, D-dimer, beta TG, PF-4, and platelet surface expression of GMP-140 and receptors for fibronectin, thrombospondin, and vWF were not measurable. A sustained mild decrease in hematocrit levels in six calves with the Cleveland Clinic-Nimbus total artificial heart for 11-120 days was attributed to an increase in circulating blood volume, but not to red blood cell damage. Whole blood platelet aggregation was suppressed only for the first 3 post operative days, with decreased GPIIbIIIa expression. Polymorphonuclear phagocytosis, chemotaxis, and superoxide anion production were not altered. Device infection and thromboembolism occurred in one of 13 cases overall.
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PMID:A comprehensive hematologic study in calves with total artificial hearts. 857 3

For rehabilitation training it is recommended that the intensity of exercise should be distinctly below the individual anaerobic threshold (IAT). We investigated platelet activity, reactivity and platelet-leukocyte conjugate formation following a stardardized treadmill (TR) ergometer test at 90% IAT for 60-120 min. Seventeen healthy male non-smokers underwent TR. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Platelets were detected flow cytometrically by CD41 in whole blood, activated platelets by CD62P. In addition, stimulation of platelets in vitro with 7.5 microM TRAP-6 was performed. For testing platelet-leukocyte conjugates, antibodies against CD45 and CD41 were used. After TR the percent of non-stimulated CD62P-positive platelets (%PC) remained unchanged (1.65 +/- 0.56 to 1.73 +/- 0.79%PC) (mean +/- SD). In contrast, an increase (P<0.05) from 31.9 +/- 13.5 to 37.4 +/- 15.0 %PC in CD62P, TRAP-6 stimulated and enhanced (P<0.01) platelet-leukocyte conjugates (11.7 +/- 3.7 to 16.1 +/- 6.9, CD41-%PC) after TR were observed. Both changes were independent of thrombin generation measured by F1+2 and TAT, and reversible after 2 h. Long-term exercise (90% IAT) on a treadmill ergometer only leads to a moderate increase of platelet reactivity and platelet-leukocyte conjugates. The determination of platelet-leukocyte conjugates may offer the possibility to detect an early activation stage of platelets in vivo.
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PMID:Platelet activity, sensitivity to agonist, and platelet--leukocyte conjugate formation after long-term exercise. 1218 12

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories-coagulation (thrombin-antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems.
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PMID:Hemocompatibility of silicon-based substrates for biomedical implant applications. 2128 75

Clinical xenotransplantation will only be feasible when present limitations can be controlled sufficiently. Activation of endothelium and complement as well as coagulopathy and thrombotic microangiopathy (TMA) is important barriers. Transgenic expression of hTBM on porcine endothelial cells is a reasonable approach to reduce activation of haemostasis. Endothelial cells from wild-type pigs as well from pigs expressing hTBM alone or in combination with hCD46 and knockout of the alpha-1,3,-galactosyltransferase (GTKO) were perfused with platelet-rich plasma in a microfluidic flow chamber. Platelet aggregation and activation, coagulation, complement and endothelial cell activation were assessed. Perfusion of wild-type porcine aortic endothelial cells (PAEC) resulted in distinct platelet aggregation. Expression of hTBM in either mono-transgenic or triple-transgenic (GTKO/hCD46/hTBM) PAEC showed significantly reduced or absent platelet aggregation. Flow cytometric analysis of platelets showed an increased CD62P expression in wild-type PAEC and significantly reduced expression in mono- or triple-transgenic PAEC. Activation of coagulation measured by TAT occured in WT PAEC and was clearly reduced in hTBM and GTKO/hCD46/hTBM PAEC. Activation of complement and endothelial cells was only reduced in GTKO/hCD46/hTBM but not in PAEC expressing hTBM alone. Expression of hTBM was able to prevent activation of coagulation and platelet aggregation in mono- and triple-transgenic PAEC, while activation of complement and endothelial cells was not reduced in mono-transgenic PAEC.
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PMID:Expression of human thrombomodulin on porcine endothelial cells can reduce platelet aggregation but did not reduce activation of complement or endothelium - an experimental study. 3192 34