Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary deficiencies of coagulation inhibitors like antithrombin III, protein C and protein S lead to an enhanced incidence of thromboembolic complications. Recently, acquired deficiencies of protein S were described in several disease states in which thromboembolic complications frequently occur. These acquired protein S deficiencies reach--in part--the extent realised by hereditary protein S deficiency. Thus, acquired protein S deficiencies seem to be one source of thromboembolic complications occurring in nephrotic syndrome, acute phase reactions, malignancy and pregnancy. In this presentation disease states accompanied by acquired protein S deficiency and the mechanisms leading to these alterations are discussed.
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PMID:Acquired protein S deficiency. 139 20

Inherited hypercoagulable states such as protein C, protein S, and antithrombin III deficiencies account for 15% to 20% of recurrent thromboembolic episodes. A common risk profile is associated with these disorders and guides the use of laboratory screening. The use of anticoagulants in inherited hypercoagulable states varies with a patient's personal and familial history of thrombosis. Special consideration is given to the need for anticoagulants perioperatively and during pregnancy.
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PMID:Inherited hypercoagulable states: questions and controversies. 139 75

Effects of human placental calphobindin II (CPB-II) on the protein C activation and prothrombin activation on the cell surface of cultured calf pulmonary arterial endothelial cells have been investigated. CPB-II inhibited thrombin generation by factor Xa bound to the surface of the cultured endothelial cells in a dose-dependent manner. The amount (IC50) of CPB-II causing the inhibition at 50% was estimated to be approximately 10 nM. CPB-II was found to be ineffective, however, in the protein C activation by thrombin-thrombomodulin (TM) complex on the cell surface. Assay using purified TM revealed that CPB-II was able to exhibit the inhibitory potency for the protein C activation exclusively in the reconstituted system with negatively charged phospholipids. These results suggest that the neutral phospholipids participate in the protein C activation through the thrombin-TM system on the endothelial cell surface. The ability of CPB-II to inhibit procoagulant activity without affecting anticoagulant activity on the cultured endothelial cells is probably related to its potential physiological function, while it is able to exert various degrees of influence upon these activities in blood coagulation by interacting with negatively charged phospholipids in vitro.
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PMID:Effects of calphobindin II (annexin VI) on procoagulant and anticoagulant activities of cultured endothelial cells. 139 5

In a wide variety of nitrogen-fixing organisms among the Purple Bacteria (large division of Gram-negative bacteria) the nitrogen fixation (nif) operons are transcribed by an alternative holoenzyme form of RNA polymerase, sigma 54-holoenzyme. Transcription depends on the activator protein NIFA (nitrogen fixation protein A), which catalyzes isomerization of closed complexes between this polymerase and a promoter to transcriptionally productive open complexes. NIFA-mediated activation of transcription from the nifH promoter of Klebsiella pneumoniae is greatly stimulated by the integration host factor IHF, which binds to a site between the upstream binding site for NIFA and the promoter, and bends the DNA. IHF fails to stimulate activation of transcription from this promoter by another activator of sigma 54-holoenzyme, NTRC (nitrogen regulatory protein C), which lacks a specific binding site in the nifH promoter region. As predicted, if the IHF-induced bend facilitates interaction between NIFA and sigma 54-holoenzyme, substitution of an NTRC-binding site for the NIFA-binding site allowed IHF to stimulate NTRC-mediated activation of transcription from the nifH promoter. The stimulation was of the same order of magnitude as that for NIFA in the native configuration of the promoter-regulatory region (up to 20-fold). With purified NTRC and the substitution construct we could demonstrate that stimulation by IHF in a purified transcription system was comparable to that in a crude coupled transcription-translation system, indicating that the stimulation in the crude system could be accounted for by IHF. The IHF stimulation was observed on linear as well as supercoiled templates, indicating that the geometric requirements are relatively simple. We have attempted to visualize the arrangement of proteins on DNA fragments carrying the nifH promoter-regulatory region of K. pneumoniae by electron microscopy. IHF stimulated NIFA-mediated activation of transcription from the nifH and nifD promoters of Bradyrhizobium japonicum and less so from the nifH promoters of Rhizobium meliloti and Thiobacillus ferrooxidans, consistent with previous observations that stimulation is greatest at promoters that are weak binding sites for sigma 54-holoenzyme in closed complexes.
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PMID:Role of integration host factor in stimulating transcription from the sigma 54-dependent nifH promoter. 140 79

Factors and inhibitors of coagulation and fibrinolysis were investigated on admission in 57 patients with acute leukaemia and they were correlated to the occurrence of haemorrhage. Coagulation disturbances were found in 98%. Seventeen of the patients with haemorrhagic symptoms had major bleeding. Severe thrombocytopenia (< 20 x 10(9)/l) was found in 16%. Patients with major bleedings had significantly lower concentrations of prothrombin complex, fibrinogen, protein C and platelets. Low levels of antiplasmin and fibrinogen were characteristic of 'bleeders' with promyelocytic and lymphoblastic leukaemia. We found a positive correlation between vWF:Ag and leukaemic cell count especially in lymphoblastic leukaemia (ks = 0.72). Reduced levels of antithrombin indicated a poorer prognosis.
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PMID:Bleeding complications and coagulopathy in acute leukaemia. 140 6

Skin necrosis similar to that induced by warfarin was seen in a patient who had never received the drug but who was vitamin K-deficient due to malnutrition and prolonged treatment with broad-spectrum antibiotics. He also had end-stage renal failure and was receiving prophylactic subcutaneous heparin therapy because of immobilization. His plasma protein C antigen level and, disproportionately, his plasma protein C functional activity were decreased. Both protein C values improved after vitamin K therapy, discontinuation of heparin, and initiation of hemodialysis. We surmise that skin necrosis occurred as a result of protein C deficiency caused by vitamin K depletion. Production of abnormal (descarboxy) protein C/protein S due to vitamin K deficiency and increased protein C inhibitory activity associated with renal failure and/or heparin administration may have contributed to the clinical picture. This rare but serious complication of a relatively common disorder, viz., vitamin K deficiency, reinforces the importance of vitamin K supplementation in malnourished patients who receive long-term antibiotic maintenance therapy.
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PMID:Skin necrosis and protein C deficiency associated with vitamin K depletion in a patient with renal failure. 825 85

Protein C inhibits coagulation and promotes fibrinolysis. This New England study investigated the association between protein C deficiency and pregnancy loss, thrombosis in pregnancy, and thrombosis with oral contraceptives (OCs). 15 protein C-deficient patients and 37 controls from a single kindred were studied. An obstetric history was obtained by telephone. Data were analyzed by logistic regression, Fisher's exact test, and Student t test. The protein C-deficient women experienced a 33% pregnancy loss vs 19% among the controls (not significant). Thromboembolism during pregnancy in protein C-deficient women was 33% (45% in those not receiving prophylactic anticoagulation) vs 5% in the controls (odds ration 7.37, p=0.026). 5 of 12 protein C-deficient women using OCs developed thrombosis vs. none of the 33 controls. The risk of thrombosis for protein C-deficient women using OCs is increased (p0.001). Perinatal outcome is not statistically different with protein C deficiency. Protein C deficiency increases the risk of thrombosis during pregnancy and while taking OCs. Prophylactic heparin is suggested during pregnancy for protein C-deficient women with personal or family histories of thrombosis. Oral contraception is not advised.
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PMID:Pregnancy loss and thrombosis with protein C deficiency. 141 34

Most people who experience venous thrombosis have normal hemostasis. Some people have inherited deficiencies of protein C, protein S, and antithrombin iii. They tend to have deep venous thrombosis which increases their risk for pulmonary emboli. Some acquired disorders which predisposes people to thrombosis include defective fibrinolysis which often occurs after surgery or infection, Trousseau's syndrome (excessive coagulant activity linked with adenocarcinoma), and lupus anticoagulant which is an immunoglobulin G or M antibody directed against negatively charged phospholipids. Hormones and probably not a dilution effect reduces free and bound protein S levels during pregnancy. Functional protein S activity is still 40-50% below normal levels 1-3 days after delivery. This decrease appears to protect against bleeding but does have venous thrombosis and pulmonary emboli during pregnancy as side effects. Non-oral-contraceptive (OC) users have greatly higher protein S levels than do OC users (28.6 mcg/ml vs. 24.3 mcg/ml; p.005) which gives more credence to the belief that hormones are responsible for the fall in protein S activity during pregnancy. OCs reduce free and total protein S levels almost 20%. Smoking may even further reduce these levels in women during pregnancy and who use Ocs. Women who have had venous thrombosis should not use OCs. Physicians should also consider family history especially age of affected family member, severity of thrombotic episodes, and the clinical setting. They should look for an underlying abnormality in patients who develop thrombosis while using OCs. If thrombosis develops during pregnancy, physicians should call for a venogram, venous duplex scanning, and, if required, invasive tests. The most sensible treatment is intravenous heparin for 5-7 days then therapeutic doses of heparin. Heparin therapy should stop before delivery and be reinstituted shortly thereafter and continued throughout the postpartum period. Physicians should take extra precautions when performing surgery on an OC user.
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PMID:Recent advances in understanding clotting and evaluating patients with recurrent thrombosis. 141 44

A recent cross sectional study on symptomatic acute deep vein thrombosis at the National University Hospital (NUH) in Singapore found a frequency rate of 0.79 per 1000 patient admissions. A total of 39 patients were accrued over 18 months, 36 with deep vein thrombosis alone and three complicated by pulmonary embolism. No sex or ethnic predilection was observed in this cohort of hospitalised patients. Twenty-eight (71.8%) patients were 40 years or older. Majority (89.7%) of patients had at least two predisposing factors. While prolonged bedrest and operative procedures featured equally frequently in patients above and below 40 years, neoplasms were predominantly associated with the former and protein C or S deficiency primarily with the latter. The exhaustive laboratory confirmation of an inherent thrombotic tendency is recommended only for patients below 40 years of age.
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PMID:Acute deep vein thrombosis in hospital practice. 141 82

We describe a patient who developed a severe coagulopathy after being bitten by a red-necked keelback snake (Rhabdophis subminiatus), a species which is generally considered non-venomous. The patient's blood was incoagulable due to complete depletion of fibrinogen. Comprehensive coagulation studies were performed to identify the mechanism(s) by which the snake toxin caused the coagulopathy. It was found to contain a potent prothrombin activator, probably an activator of protein C and possibly also a factor X activating enzyme. The fibrinolysis was secondary to intravascular fibrin formation; there were no indications for a direct fibrinogenolytic activity in the snake toxin. Remarkably, there was virtually no consumption of antithrombin III, despite extensive thrombin formation; this feature appears to be not uncommon after snake bites, but is still unexplained.
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PMID:Haemostatic effects in vivo after snakebite by the red-necked keelback (Rhabdophis subminiatus). 142 Aug 21


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