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)

Protein S and C4b-binding protein (C4BP) form a tight complex (Kd approximately 0.6 nM) the physiologic purpose of which is unknown. The participation of protein S in this complex was investigated using site-specific mutagenesis. Normal recombinant human protein S (rHPS) and five specifically mutated protein S analogs were expressed in transformed human kidney 293 cells and the following properties were characterized: solution-phase C4BP binding, ability to be cleaved by thrombin, ability to act as a cofactor in the activated protein C-catalyzed inactivation of factor Va, and gamma-carboxyglutamic acid content. In some cases, beta-hydroxyaspartic acid plus beta-hydroxyasparagine content was also determined. Binding studies indicated that while clearly important for a high affinity interaction, the amino acid sequence Gly605-Ile614 identified by Walker (Walker, F J. (1989) J. Biol. Chem. 264, 17645-17648) does not account for all the binding energy of the HPS-C4BP interaction. All mutants perturbed in this region or lacking it altogether displayed reduced C4BP binding, and some retained anticoagulant cofactor function. Neither human factor X nor human steroid-binding protein had any measurable ability to compete with plasma HPS for C4BP binding. Furthermore, bovine protein S and a rHPS analog with bovine sequence from Gly597-Trp629 bound to human C4BP with the same affinity as did HPS, and both proteins substituted effectively for HPS as a cofactor for activated protein C in an otherwise human anticoagulation system. Together these results suggest that optimal binding of protein S to C4BP requires the putative alpha-helix Gly605-Ile614, as well as other undetermined regions of protein S, and that the regions of HPS responsible for C4BP binding and activated protein C cofactor function are structurally isolated.
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PMID:Binding of protein S to C4b-binding protein. Mutagenesis of protein S. 153 19

Hereditary deficiency of protein C, protein S or antithrombin III has been associated with an increased incidence of venous thrombosis or pulmonary embolism. The relationship between these deficiencies and the development of arterial thrombosis is a matter of current investigation. We retrospectively studied the occurrence of arterial thrombosis in 92 symptomatic patients belonging to a group of 160 with a confirmed diagnosis of hereditary deficiency of one of the physiologic clotting inhibitors. Seventeen of them experienced at least one arterial thrombotic event. This indicates that about one out of five of the symptomatic patients had experienced arterial thrombosis. The control group consisted of 92 sex and age matched (+/- 5 years) patients with no clotting deficiency who had experienced in the same period at least one episode of deep vein thrombosis or pulmonary embolism. Only one of them had developed arterial thrombosis. Ischemic stroke, myocardial infarction, upper and lower limb arterial thrombosis, and mesenteric artery occlusion occurred regardless of the type of defect taken into account; mean age of about 37.05 +/- 23 years (mean +/- SD). In some cases, arterial thrombosis was fatal. The overall number of venous thrombotic events in the 92 symptomatic patients of this study was much higher than that of arterial thrombosis, with a ratio of 24 to 1. The use of long-term anticoagulant therapy in our group of patients seemed to be able to prevent recurrences of both arterial and venous thrombosis.
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PMID:Occurrence of arterial thrombosis in a cohort of patients with hereditary deficiency of clotting inhibitors. 153 14

We examined the relationship between free protein S deficiency and cerebrovascular disease by reviewing the records of all patients with the diagnoses of cerebral thrombosis, cerebral embolism, and cerebral vascular occlusion who were referred for coagulation studies over a 12-month period. We assayed for free protein S antigen, protein C antigen, and antithrombin III and tested for lupus-like anticoagulant and anticardiolipin antibody. Twenty-two of 267 patients (8.2%) admitted with thrombotic strokes were referred for coagulation studies. Free protein S antigen was significantly lower in women than in men (62 +/- 25% versus 88 +/- 24%, p = 0.03; n = 11 in each group). Six women had free protein S antigen levels below the range recorded for a contemporary group of 24 age-matched normal women (17 to 59% versus 70 to 102%, p less than 0.001); four of these women had cerebral arterial thrombosis and two had venous dural sinus thrombosis. The six women were aged 29 to 55 at the time of their first strokes; two had family members with protein S deficiency, and one of these had died of a stroke at age 52. Other abnormalities in this population included a positive test for lupus-like anticoagulant or anticardiolipin in five patients, a modest decrease in protein S in two men, and one patient with an isolated deficiency of antithrombin III. We conclude that protein S deficiency may be an important risk factor for stroke in middle-aged women but this requires confirmation by prospective studies in unselected patients.
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PMID:Protein S deficiency in middle-aged women with stroke. 153 5

Protein C (PC) and protein S (PS) are components of a potent, natural anticoagulant system. A deficiency of one of these two inhibitors is associated with thrombotic events in young people. A significant reduction in functional PS activity has been observed during normal pregnancy, and recurrent fetal loss may occur in women with lupus anticoagulant (LA) inhibitor. We measured functional PS activity and free PS antigen in 16 non pregnant patients with LA inhibitor and in 17 normal women as controls. A significant difference was observed between patients and controls in functional PS activity (65 +/- 23% vs 87 +/- 15%, p = 0.02) but not in free PS antigen (88 +/- 17% vs 93 +/- 17%). Functional PS activity decreased only in six patients (37%). Removal of IgG from plasma reduced the difference in functional PS activity between patients and controls. Immunologic IgG levels did not correlate with anti-phospholipid antibodies (APA) activities, activated partial thromboplastin time/kaolin clotting time (aPTT/KCT) data or functional PS activity.
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PMID:Functional protein S in women with lupus anticoagulant inhibitor. 153 34

To investigate levels of coagulation inhibitors in sera from patients with Clostridium difficile-associated diarrhoea and colitis, commercially available antigen assays were used for immunochemical determination of antithrombin III, protein C and free protein S. Sera from patients with Clostridium difficile-associated diarrhoea and colitis showed significantly lowered levels of all measured inhibitors as compared to controls (Student's t test). Protein C (mean +/- SD): 0.70 +/- 0.30 vs. 1.28 +/- 0.23, t = 6.61, p less than 0.001; antithrombin: 0.70 +/- 0.21 vs. 0.90 +/- 0.17, t = 3.12, p less than 0.01; free protein S: 0.27 +/- 0.06 vs. 0.37 +/- 0.08, t = 3.7, p less than 0.001. Infection with C. difficile may lead to loss of coagulation inhibitors and constitutes a risk for thromboembolic complications.
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PMID:Low levels of coagulation inhibitors in patients with Clostridium difficile infection. 153 51

Protein C and S are important factors in blood coagulation reported in many papers about people who suffered from thromboembolic diseases related to inherited or acquired deficiencies. Homozygous protein C/S deficiency is lethal in most cases without therapy. Heterozygous deficiency is moderate and complications occur between the 20.-50. year of age. Acquired protein C/S deficiency is a strong parameter for liver function. The typical clinical manifestations of protein C/S deficiencies are superficial and deep leg vein thrombosis, thrombosis of the mesenterial, cerebral, renal and axillary veins, portal vein thrombosis and pulmonary embolism. Most of the affected people live disease free over a longer period and develop thromboembolic complications during and after trauma, surgical interventions, pregnancy and puerperium. We report our experience with a 60 years old male who had developed a severe bilateral iliofemoral vein thrombosis with signs of pulmonary embolism after total hip replacement. An extended functional protein C deficiency (type II) was investigated by coagulation tests (Protein C Reagent, coagulometric from Behring Institute). A second female patient developed a descending iliofemoral vein thrombosis during pregnancy. Venous thrombectomy with arteriovenous fistula was performed, but reocclusion occurred after delivery. Redo-surgery was undertaken and a second reocclusion took place 10 days later. Further lysis therapy was not able to reopen the venous system. Whereas immunological and functional protein C levels showed normal ranges, the functional protein S level was markedly reduced (IL-Instrumentation Laboratory Protein S-Test).
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PMID:[The clinical importance of protein C and S deficiency for surgical patients]. 153 92

Anabolic steroids are known to increase the plasma concentrations of certain plasma proteins. In four patients given treatment with danazol, an attenuated androgen, the concentrations of heparin cofactor II, Hageman factor (factor XII), protein C, and both free and total protein S increased significantly when tested 39 to 103 days after the start of therapy. The titers of these proteins in samples obtained 21 days to 5 years after therapy was discontinued were similar to those before treatment, except for total protein S, the titer of which remained elevated. No significant changes in the titers of C4b binding protein or plasma plasmin inhibitory activity were found.
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PMID:Some clotting factors in plasma during danazol therapy: free and total protein S, but not C4b-binding protein, are elevated by danazol therapy. 153 44

Blood coagulation and fibrinolytic inhibitors and the balance between and within the two systems were investigated in 26 normal pregnant women during pregnancy and the puerperium. The concentration of the coagulation inhibitors antithrombin and protein C remained within normal levels, whereas the mean level of free protein S showed a significant decrease from 0.26 U/mL in early pregnancy to 0.14 U/mL in week 35. At the same time, soluble fibrin levels increased from 9.2 to 13.4 nmol/L and thrombin-antithrombin complexes increased from 3.1 to 7.1 micrograms/L; both are indicators of thrombin activity. A concurrent increase in the levels of the fibrinolytic inhibitors plasminogen activator inhibitor-1 and -2 from 7.4 to 37.8 AU/mL and 31 to 160 micrograms/L, respectively, suggests a decrease in fibrinolytic activity. However, the levels of fibrin D-dimer, ie, fibrin split products, also increased in parallel from 91 to 198 micrograms/L, suggesting that fibrinolysis is present. Thus, a balance normally exists, which is probably why thrombotic events are rare during pregnancy.
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PMID:Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. 153 80

Platelet suspension was obtained from normal platelet rich plasma (PRP) by the gel filtration method using Sepharose 2B and platelet pellet was prepared from the platelet suspension after centrifugation. A platelet preparation was prepared from the solubilized platelet pellet. Purified protein S was obtained from plasma and platelet preparation using immuno-affinity column chromatography. Total antigen of protein S was measured by enzyme immunoassay and activity of protein S was measured as a cofactor of activated protein C. The ratio of purified protein S activity to total antigen in normal plasma and platelet was 2.3 and 2.1, respectively. According to immunoblot and crossed immunoelectrophoresis studies, the molecular weight of platelet protein S was different from that of plasma protein S. Localization of protein S in platelet alpha-granules was demonstrated by immunoelectronmicroscopy.
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PMID:[Is platelet protein S different from plasma protein S in human being?]. 153 88

In 107 asymptomatic and untreated patients with inherited syndromes associated with thrombophilia (antithrombin III, protein C and protein S deficiencies), we compared in parallel two plasma peptides which reflect activation of the common coagulation pathway: the prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA). Both F1 + 2 and FPA were measured with simple, commercially available ELISA methods. High levels of F1 + 2 or FPA were found in about one fourth of the patients as a whole. When patients were divided according to the type of inherited thrombophilic syndrome, it appeared that F1 + 2 was more frequently elevated in protein C and protein S deficiencies than in antithrombin deficiency; and that, in general, it was no more frequently elevated than FPA. Although our data confirm the existence of a procoagulant imbalance in inherited thrombophilic syndromes due to defects of natural anticoagulant proteins, they do not confirm that such imbalance can be more frequently diagnosed by measuring F1 + 2 levels, particularly in patients with antithrombin deficiency.
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PMID:Markers of procoagulant imbalance in patients with inherited thrombophilic syndromes. 153 36


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