Disease relevance of PFDN4

• Absence of thrombosis in subjects with heterozygous protein C deficiency [1].
• Recombinant human activated protein C for severe sepsis [2].
• Resistance to activated protein C as a basis for venous thrombosis [3].
• Although considerable progress has been made during the past two decades in the use of androgens to prevent attacks of hereditary angioedema, replacement of the deficient C1-inhibitor protein would provide a useful menas of treatment once an attack has begun [4].
• Inhibition of protein C activation by endothelial cells in the presence of lupus anticoagulant [5].

Psychiatry related information on PFDN4

• Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development [6].
• Addition of protein C resulted in a dose-dependent rise in pain threshold towards the level observed in control animals treated with saline instead of carrageenan (pain threshold after 800 IU/kg protein C = 62.9 +/- 2.3% of pretreatment level), demonstrating an antinociceptive effect [7].
• Home treatment with protein C concentrate allowed a near-normal life-style for patients who otherwise would be hospitalized for long periods of time [8].
• However, for plasma samples, with a limited sample reaction time, the sensor produced only 30% of the signal intensity of PC in buffer [9].
• In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia [10].

High impact information on PFDN4

• A mutation in the surfactant protein C gene associated with familial interstitial lung disease [11].
• The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed [12].
• METHODS: DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy [12].
• Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years [12].
• A specific point mutation in the gene coding for coagulation factor V is associated with resistance to degradation by activated protein C, a recently described abnormality of coagulation that may be associated with an increased risk of venous thrombosis [13].

Chemical compound and disease context of PFDN4

• Hereditary angioedema is an inherited disease transmitted as an autosomal dominant trait and characterized by deficient activity of C1 inhibitor, a glycoprotein that limits intravascular activation of complement [14].
• Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis [15].
• Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans [16].
• Coumarin prophylaxis for fulminant purpura syndrome due to homozygous protein C deficiency [17].
• To test this hypothesis, the autolysis loops of both thrombin and the anticoagulant serine protease-activated protein C were replaced with the corresponding loop of factor Xa [18].

Biological context of PFDN4

• Nucleotide sequence analysis of C-1 revealed that it contains a helix-loop-helix domain, indicating that it may be a transcription factor [19].
• These results suggest that the C-1 gene product may function as a transcription factor related to the cell cycle [19].
• Expression of the C-1 gene was transiently induced early in the G0-to-S phase transition in two normal human (OUMS-24 and HSF-412) and a non-tumorigenic immortal human (OUMS-24F) fibroblast cell lines, while the other immortal SUSM-1 cells highly expressed the C-1 gene in the middle G1 phase [19].
• Protein C is the zymogen of a vitamin K-dependent serine protease involved in blood coagulation [20].
• Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy [21].

Anatomical context of PFDN4

• Truncated cardiac myosin-binding protein-C does not act as a "poison polypeptide," since it seems not to be incorporated into the sarcomere in significant amounts [22].
• Cardiac myosin binding protein-C (cardiac MyBP-C, cardiac C protein) belongs to a family of proteins implicated in both regulatory and structural functions of striated muscle [23].
• The centrosomal protein C-Nap1 is required for cell cycle-regulated centrosome cohesion [24].
• Proteolytic maturation of protein C upon engineering the mouse mammary gland to express furin [25].
• Coperfusing diisopropylphospho-thrombin with active thrombin lowers the amount of protein C activation in the myocardium [26].

Associations of PFDN4 with chemical compounds

• However, current users of estrogen alone had higher triglyceride, factor VII, and protein C levels than either nonusers or current users of estrogen with progestin [27].
• Genes encoding fusions between the maize regulatory protein C1 and the yeast transcriptional activator GAL4 and mutant C1 proteins were assayed for their ability to trans-activate anthocyanin biosynthetic genes in intact maize tissues [28].
• During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein [15].
• The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays) [29].
• Protein C is a vitamin-K-dependent plasma glycoprotein that when activated inhibits coagulation by selectively inactivating the active forms of factor V and factor VIII [30].

Physical interactions of PFDN4

• Although the thrombin/thrombomodulin complex is considered the physiological activator of protein C, factor Xa (f.Xa) can also activate protein C in a reaction that is potentiated by glycosaminoglycans [31].

Regulatory relationships of PFDN4

• INTRODUCTION: Increased coagulation activity due to coronary thrombosis in a ruptured plaque should result in activation of the protein C anticoagulant system with formation of complexes between activated protein C (APC) and the protein C inhibitor (PCI), which reflects coagulation activity [32].

Other interactions of PFDN4

• Recombinant human activated protein C upregulates the release of soluble fractalkine from human endothelial cells [33].
• CONCLUSIONS: The data do not allow the direct association of the FII or FX increase with a defect in the protein C system in the current conditions [34].
• We found age- and sex-related differences and estimated the prevalence of deficiencies of protein C (0.13%), antithrombin (0.15%), protein S (1.12%), and plasminogen (4.29%) [35].
• OBJECTIVE: We evaluated the effect of factor VIII, II, or X (FVIII, FII, or FX) levels on activated protein C resistance technique and its association with the resistant phenotype [34].
• Functional Characterization of Heterogeneous Nuclear Ribonuclear Protein C1/C2 in Vitamin D Resistance: A NOVEL RESPONSE ELEMENT-BINDING PROTEIN [36].

Analytical, diagnostic and therapeutic context of PFDN4

• Therapeutic levels of human protein C in rats after retroviral vector-mediated hepatic gene therapy [37].
• Successful treatment of homozygous protein C deficiency by hepatic transplantation [38].
• Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study [39].
• Severe acquired protein-C deficiency in meningococcaemia is usually associated with substantial mortality: in survivors, skin grafts, amputation, and end-organ failure are not uncommon [16].
• The supratherapeutic INR was explained by the greatly reduced levels of factor VII, which correlated closely with protein C levels; therefore, the high INR was a surrogate marker for severely reduced protein C activity [40].

References