APO‐1 (Fas/CD95), a member of the tumor necrosis factor receptor superfamily, induces apoptosis upon receptor oligomerization. In a search to identify intracellular signaling molecules coupling to oligomerized APO‐1, several cytotoxicity‐dependent APO‐1‐associated proteins (CAP) were immunoprecipitated from the apoptosis‐sensitive human leukemic T cell line HUT78 and the lymphoblastoid B cell line SKW6.4. CAP1–3 (27–29 kDa) and CAP4 (55 kDa), instantly detectable after the crosslinking of APO‐1, were associated only with aggregated (the signaling form of APO‐1) and not with monomeric APO‐1. CAP1 and CAP2 were identified as serine phosphorylated MORT1/FADD. The association of CAP1–4 with APO‐1 was not observed with C‐terminally truncated non‐signaling APO‐1. In addition, CAP1 and CAP2 did not associate with an APO‐1 cytoplasmic tail carrying the lprcg amino acid replacement. Moreover, no APO‐1‐CAP association was found in the APO‐1+, anti‐APO‐1‐resistant pre‐B cell line Boe. Our data suggest that in vivo CAP1–4 are the APO‐1 apoptosis‐transducing molecules.
Thrombin is the pivotal enzyme in the biochemistry of secondary hemostasis crucial to maintaining homeostasis of hemostasis. In contrast to routine coagulation tests (PT or aPTT) or procoagulant or anticoagulant factor assays (e.g. fibrinogen, factor VIII, antithrombin or protein C), the thrombin generation assay (TGA), also named thrombin generation test (TGT) is a so‐called “global assay” that provides a picture of the hemostasis balance though a continuous and simultaneous measurement of thrombin formation and inhibition. First described in the early 1950s, as a manual assay, efforts have been made in order to standardize and automate the assay to offer researchers, clinical laboratories and the pharmaceutical industry a versatile tool covering a wide range of clinical and non‐clinical applications. This review describes technical options offered to properly run TGA, including a review of preanalytical and analytical items, performance, interpretation, and applications in physiology research and pharmacy.
Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID‐19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.
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