Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although in vitro experiments have established that extrinsic pathway inhibitor (EPI) is the only known plasma inhibitor of factor VIIa-tissue factor (TF) catalytic activity of potential physiologic significance, evidence of its function in vivo has been lacking. TF-induced intravascular coagulation may occur in patients despite normal plasma levels of EPI and, in our earlier studies, normal plasma EPI levels did not protect rabbits from intravascular coagulation induced by an infusion of purified TF (1 microgram/kg). Studies have now been carried out in which plasma EPI levels were reduced in rabbits to below 20% of the initial level by injection of anti-rabbit EPI IgG. Infusion into such animals of purified rabbit TF apoprotein (0.25 microgram/kg) reconstituted into phospholipid vesicles induced substantial disseminated intravascular coagulation. Infusion of control saline or phospholipid vesicles not containing TF was without significant effect as was infusion of TF (0.25 microgram/kg) into animals injected with nonimmune goat IgG. These data establish that EPI can dampen TF-induced intravascular coagulation in rabbits. They support the hypothesis that EPI plays a significant role in regulating coagulation resulting from the exposure of blood to trace concentrations of TF during the illnesses and minor injuries of normal existence.
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PMID:Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant. 189 82

The apoprotein (AP) of tissue factor (TF) has been purified 72,000-fold to homogeneity from human placenta using acetone delipidation, sodium deoxycholate (DOC) extraction, Sephacryl S-300 column chromatography, preparative polyacrylamide-gel electrophoresis (PAGE) in DOC and tryptic digestion. The purified AP had an apparent molecular weight of 54,000 by sodium dodecyl sulfate/PAGE. A radioimmunoassay (RIA) for quantitation of the TF-AP using an antibody against this purified AP of TF was devised which was sensitive enough to measure as small a quantity as 100 pg/ml of TF-AP accurately with high reproducibility. In addition to TF clotting activity (TFA), the immunoreactive TF-AP (IR-TFR) in the homogenates of leukemic leukocytes from patients with acute non-lymphoid leukemia (ANLL) was determined using this RIA. In 30 patients with ANLL, the mean IR-TFR with standard deviation (SD) of 21 cases with DIC was 157.9 +/- 188.1 ng/10(8) cells, which was significantly higher than that (37.1 +/- 29.9 ng/10(8) cells) of 9 cases with no DIC during remission induction chemotherapy (p less than 0.01).
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PMID:Radioimmunoassay of human tissue factor. 373 65

Increasing evidence [1, 2, 3] demonstrates the clinical importance of monocyte thromboplastin synthesis in the pathogenesis of thrombosis and disseminated intravascular coagulation. Among the first to describe this was the group of the late F Josso [4, 5]. In addition, monocytes and macrophages appear to contribute to fibrin deposition in inflammatory lesions [6, 7]. Several procoagulant substances have been reported to appear in monocyte cultures. Among these, thromboplastin is the most potent and probably also the most important and well studied. Based as it is on our own work, this brief review will deal only with thromboplastin. It is a phospholipid-protein complex, consisting in human material of one species of protein (apoprotein III) mol. wt. approximately 52,000 surrounded by phospholipids [8] in an optimal molecular ratio of apoprotein:phospholipids of approximately 1:80 [9]. Apoprotein III is an integral membrane glycoprotein which apparently is located mainly on the outside of the plasma membrane. The molecular weight has recently been confirmed in our laboratory by Western blotting, using a monoclonal antibody to apoprotein III developed here (Johnsen, unpublished).
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PMID:The role of cellular cooperation in thromboplastin synthesis. 636 91

To investigate the clinical significance of determination of plasma tissue factor (TF) antigen, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for plasma TF, using two different monoclonal antibodies against TF apoprotein, 6B4 (catching antibody) and 5G9 (detecting antibody), and tetramethyl benzidine/H2O2 as substrates. Titration curves of recombinant human TF in buffer containing Triton X-100 were linear within the range from 50 to 2000 pg/ml. The total assay time was 3 h. Ultracentrifugation and immunoblot analysis indicated that human plasma and urine contained 50,000 g sedimentable and non-sedimentable forms of TF, both of which were detected by our ELISA method. Plasma and urine concentrations of TF in healthy subjects and patients with various diseases were measured by the ELISA method. In healthy subjects, plasma and urinary TF levels were found to be 149 +/- 72 pg/ml (n = 30) and 175 +/- 60 pg TF/urine creatinine mg (n = 95), respectively. TF was increased in plasma of patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, vasculitis associated with collagen diseases, diabetic microangiopathy and chronic renal failure receiving haemodialysis, but not in the plasma of endotoxaemic patients without DIC. The plasma TF/serum creatinine ratio did not show a positive correlation. Measurement of TF antigen in plasma may be useful for evaluating the endothelial damage and cell destruction in TF-containing tissues.
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PMID:Determination of plasma tissue factor antigen and its clinical significance. 794 77

Overwhelming bacterial infection is accompanied by fever, hypotension, disseminated intravascular coagulation, and multiple organ failure leading to death in 30-80% of cases. These classical symptoms of septic shock are caused by potent cytokines that are produced in response to endotoxin released from Gram-negative bacteria. Treatments with antibodies and receptor antagonists to block endotoxin or cytokine mediators have given mixed results in clinical trials. High density lipoprotein (HDL) is a natural component of plasma that is known to neutralize endotoxin in vitro. We report here that raising the plasma HDL concentration protects mice against endotoxin in vivo. Transgenic mice with 2-fold-elevated plasma HDL levels had more endotoxin bound to HDL, lower plasma cytokine levels, and improved survival rates compared with low-HDL mice. Intravenous infusion of HDL also protected mice, but only when given as reconstituted HDL prepared from phospholipid and either HDL apoprotein or an 18-amino acid peptide synthesized to mimic the structure of apolipoprotein A-I of HDL. Intact plasma HDL was mildly toxic, and HDL apoprotein was ineffective. The effectiveness of the reconstituted peptide renders very unlikely any significant contribution to protection by trace proteins in apo-HDL. These data suggest a simple leaflet insertion model for binding and neutralization of lipopolysaccharide by phospholipid on the surface of HDL. Plasma HDL may normally act to protect against endotoxin; this protection may be augmented by administration of reconstituted HDL or reconstituted peptides.
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PMID:In vivo protection against endotoxin by plasma high density lipoprotein. 826 67