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

Three patients with an acute exacerbation of ulcerative colitis (a 40-year-old and a 31-year-old man and a 30-year-old woman) developed a protein C deficiency (serum protein C activity between 32 and 48%). In the two men the protein C deficiency was diagnosed only after the onset of severe thromboembolic complications (cavernous sinus thrombosis; pulmonary embolism) during heparin treatment. But in the woman protein C activity was measured immediately after hospital admission (in the knowledge of the first two cases) even before heparin administration was started. All three patients received treatment with sulphasalazine (3 g daily) and fluocortolone (60 mg daily), as well as full heparinization (22,500-36,000 IU daily). Protein C activity returned to normal on remission of the ulcerative colitis (in one case only after subtotal colectomy). These case reports show that acquired protein C deficiency can be reversed by rigorous treatment of the underlying disease.
 ...
PMID:[Acquired protein C deficiency in ulcerative colitis. The cause of thromboembolic complications]. 162 40

This study investigates type II protein C deficiency in a family with manifestations of both arterial and venous thrombosis. Of 64 members of the kindred, 14 have been tested and 7 have PC deficiency. Among affected individuals (n = 7), mean protein C levels by different assays were as follows: enzyme-linked immunosorbent assay (ELISA), 3.8 micrograms/mL (2.1 to 4.3 micrograms/mL); amidolytic with venom activator, 115% (60% to 140%); clotting with venom activator, 42% (23% to 59%). The mean ratio of clotting to amidolytic assays for the affected individuals was 0.37 compared with a normal range of 0.8 to 1.2. Thus, the affected individuals have normal total protein C and their activated protein C has a normal active site assessed by chromogenic substrate; however, they have markedly diminished clotting activity. Immunoassay and chromatography data suggested an abnormality of carboxylation in the gamma carboxyglutamic acid (Gla) domain. Polymerase chain reaction amplification and direct DNA sequencing of exon 2 from genomic DNA of affected individuals showed two nucleotide substitutions. One of the mutations (A----C) results in Glu20----Ala, thereby eliminating a site for vitamin K-dependent gamma-carboxylation. The other substitution (G----A) results in a Val34----Met mutation. DNA sequencing of the other exons from affected individuals has shown no further difference from that of the wild-type gene. The former mutation also removes a Bgl II restriction endonuclease site, which has allowed us to confirm the mutation in affected individuals by direct digestion and Southern hybridization of genomic DNA from family members. This is the first reported family with documented Gla domain mutations in the protein C gene.
 ...
PMID:Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations. 134 6

A CGA----TGA transition in the protein C gene, resulting in an Arg306----Term substitution, was detected in a Swedish kindred with thrombotic disease whose members exhibit plasma protein C activity/antigen levels consistent with type I protein C deficiency. Although an identical lesion has been reported previously in several Dutch families, RFLP typing indicated that the Dutch and Swedish mutations were unlikely to be identical by descent and probably arose by recurrent mutation.
 ...
PMID:Protein C deficiency and thromboembolism: recurrent mutation at Arg 306 in the protein C gene. 134 46

Racial differences in stroke are known to exist with persons in the black race having a higher morbidity, mortality and incidence of stroke compared to whites. We evaluated coagulation factors in black and white stroke patients and compared the results between races. D-dimer was elevated more frequently in blacks than whites to a statistically significant degree. There were non-significant trends for blacks to have a positive lupus anticoagulant, low protein C and protein S, higher platelet factor 4, and hyporesponsive platelets to 10 microM epinephrine. The significance of these findings in understanding racial differences in stroke is discussed.
 ...
PMID:Racial differences in coagulation studies in stroke. 135 61

Twenty-four patients presenting an acute stroke with watershed cerebral infarct on CT scan or MRI were included in this retrospective study. Age was 63 +/- 14 years (mean +/- SD), and sex ratio was 2 men for 1 woman. Main clinical features were: in anterior location, lower limb weakness and frontal syndrome with transcortical motor aphasia in left lesions or spatial dyscalculia in right ones; in posterior location, brachiofacial weakness with constant quadranopsia and hypoesthesia, and Gerstmann syndrome in left lesion. There was no distinctive feature for subcortical and multiple infarcts. In bilateral infarcts, there were one pseudobulbar syndrome, and 2 pseudo brainstem syndromes with neuropsychological signs. Aetiologies were severe carotid artery disease in 14 cases, severe cardiopathy in 6, isolated cerebral angiitis in 1, essential thrombocythemia in 1, protein C deficiency with sickle cell disease in 1, and cholesterol emboli in 1 anatomical case. CBF performed in carotid artery occlusions or tight stenoses showed evidence of haemodynamic changes. Microembolic process can be proposed in the case with cholesterol emboli. Preventive treatment is discussed.
 ...
PMID:Watershed cerebral infarcts: retrospective study of 24 cases. 135

The synthesis of a number of clotting factors takes place in a hepatocyte. Therefore, measurement of these factors in the blood have proved to be of additional value in the diagnosis and follow-up of liver diseases. In the present study we evaluated protein C level in the plasma of patients with liver cell damage due to chronic alcohol consumption. A decrease in plasma protein C concentration which correlated with clinical performance of the patients was found. Significant correlations between the level of protein C and antithrombin III, one-stage prothrombin time, factors VII and X and some biochemical tests reflecting liver cell damage were also stated. The obtained data indicate that plasma protein C level may constitute a useful marker of hepatocellular disease in alcoholics.
 ...
PMID:Plasma protein C as a marker of hepatocellular damage in alcoholic liver disease. 803 40

4 studies involving a combined oral contraceptive devised with norgestimate as the progestin and low-dose ethinyl estradiol as the estrogen, designed to have virtually no androgenic effects, are reviewed. A study of lipid metabolism found that cholesterol rose above desirable limits of 200 mg/dl in only 5% of women and fell within these limits in 25% who surpassed it. Similarly, triglycerides rose above 150 mg/dl in 5% with normal levels and fell in 28% who initially had high levels. 2 other studies documented increases in HDL and decreases in LDL, improving the HDL/LDL ratio. Coagulation factors were followed in a small series: no adverse effects on fibrinopeptide A, antithrombin III, protein C, Fibrinogen, factor VII, or factor VIII were seen in 6 months. No significant changes in mean levels of fasting glucose, insulin, hemoglobin A1C, or glucose tolerance were found. 2% of 2738 women developed abnormal fasting glucose levels after 6 months, while 35% lowered their initially abnormal glucose levels into the normal range after 6 months on the combined pill. Androgenicity was assessed by sex hormone binding globulin (SHBG) and free testosterone levels. The norgestimate pill elevated SHBG about 3-fold, lowering free testosterone. The prevalence of acne in norgestimate pill users is 2%. No change was noted in average blood pressure or weight. Similar results have been reported in studies on a triphasic norgestimate formulation. These results are optimistic for beneficial effects on major risk factors for cardiovascular disease, but large longterm epidemiological studies will have to be done to confirm them.
 ...
PMID:Long-term profile of a new progestin. 136 89

Factors affecting the production of recombinant human protein C were investigated. When recombinant cells producing human protein C were cultured with microcarrier in two different scales, we found that (1) as cells grew to confluence, specific productivity of the protein was decreased and that (2) the efficiency of gamma-carboxylation of the generated protein C was lower in a larger culture than in a smaller culture. Higher cell density was shown to influence the specific productivity unfavorably. On the other hand, the amount of oxygen supply as demonstrated by oxygen consumption rate in the Opticell culture system correlated well with the efficiency of gamma-carboxylation, suggesting that oxygen metabolism is somehow implicated in the post-translational modification of recombinant protein C.
 ...
PMID:Factors influencing expression and post-translational modification of recombinant protein C. 136 89

For the development of a perfusion culture producing recombinant human protein C, the effects of fetal calf serum and growth factors on cell growth and recombinant protein production were investigated. Although the growth of recombinant cells was stimulated by serum in a dose-dependent manner, a lower concentration of serum (2%) could support both synthesis and post-translational modification of protein C as efficiently as 10% serum. Among the growth factors tested, transferrin enhanced protein C production to the level comparable with 10% serum, while insulin was effective in maintaining cellular metabolism. Based on these results, a perfusion culture for a scale-up production of recombinant protein C was done using an Opticell culture system. A good productivity of the recombinant protein was obtained in low serum or serum-free medium for more than one month.
 ...
PMID:Production of recombinant protein C in serum-containing and serum-free perfusion culture. 136 18

Previously, two rat monoclonal antibodies where developed which bind distinct epitopes on a murine glycoprotein, P112, which is expressed primarily in lung capillary endothelium. In this paper we show that P112 is identical to the endothelial anticoagulant protein, thrombomodulin (TM). Several lines of evidence support this conclusion. First, amino acid analysis of P112 shows a high degree of homology to TM, and both molecules exhibit the same mobility in gel electrophoresis. Second, P112 and TM share reactivity for two different monoclonal antibodies. Third, purified P112, like TM, acts as a cofactor for protein C activation. Finally, two cDNA clones identified with P112 polyclonal antiserum contain sequence identity with the known TM cDNA sequence. Quantitative analysis of TM (P112) expression using a two-site monoclonal antibody assay demonstrates that significantly higher levels of TM are found in lung in comparison with other highly vascularized organs, i.e. the kidney and liver. Quantitative Northern blot data coincides with the two-site assay data and demonstrates that the high level of TM expression in lung is not due to preferential binding of the monoclonal antibodies to lung TM but rather to increased production of TM mRNA in the lung relative to other highly vascularized organs. It is suggested that expression of TM is highest in cells from continuous endothelium.
 ...
PMID:Thrombomodulin is preferentially expressed in Balb/c lung microvessels. 137 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>