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)

In 71 patients with fever and bacteremia without complications, a prospective study of acute-phase reactants is done. Raises in haptoglobin, ceruloplasmin, alpha-1-antitrypsin, protein C, beta-2-microglobulin, IgA and ferritin serum levels, together with leucocytosis and GSR, were very significant when diagnosis was done. Fibronectin, sideremia and transferrin were lowered. After 3 and 6 days of treatment haptoglobins, alpha-1-antitrypsin, protein C, ferritin, leucocytosis and GSR are lowered, while immunoglobulins, sideremia, transferrin and fibronectin raised, the latter until normalization. Fibronectin as well as changes in iron metabolism were very reliable parameters of inflammation and favorable evolution.
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PMID:[Acute-phase reactants in sepsis]. 148 35

The enzyme NAD(P)H:flavin oxidoreductase (flavin reductase) catalyzes the reduction of soluble flavins by reduced pyridine nucleotides. In Escherichia coli it is part of a multienzyme system that reduces the Fe(III) center of ribonucleotide reductase to Fe(II) and thereby sets the stage for the generation by dioxygen of a free tyrosyl radical required for enzyme activity. Similar enzymes are known in other organisms and may more generally be involved in iron metabolism. We have now isolated the gene for the E. coli flavin reductase from a lambda gt11 library. After DNA sequencing we found an open reading frame coding for a polypeptide of 233 amino acids, with a molecular weight of 26,212 and with an N-terminal segment identical to that determined by direct Edman degradation. The coding sequence is preceded by a weak ribosome binding site centered 8 nucleotides from the start codon and by a promoterlike sequence centered at a distance of 83 nucleotides. In a Kohara library the gene hybridized to position 3680 on the physical map of E. coli. A bacterial strain that overproduced the enzyme approximately 100-fold was constructed. The translated amino acid sequence contained a potential pyridine nucleotide-binding site and showed 25% identity with the C-terminal part of one subunit (protein C) of methane monooxygenase from methanotropic bacteria that reduces the iron center of a second subunit (protein A) of the oxygenase by pyridine nucleotides.
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PMID:Characterization of the flavin reductase gene (fre) of Escherichia coli and construction of a plasmid for overproduction of the enzyme. 205 Jun 27

Seventy-four patients with beta-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p less than 0.02). PC correlated with age (p less than 0.001), transfusional iron (p less than 0.001) and ferritin (p less than 0.001). It also correlated with serum albumin (p less than 0.001), prothrombin time (p less than 0.001) and fibrinogen (p less than 0.02) and with serum transaminases (GPT) (p less than 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III.
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PMID:Protein C and antithrombin III in polytransfused thalassemic patients. 310 18

Copper(I), copper(II) and silver ions have been shown to be potent inhibitors of purified soluble methane monooxygenase (MMO) of Methylococcus capsulatus (Bath). A weaker inhibition has been observed with zinc and cadmium ions. Proteins A and B of soluble MMO are unaffected by copper but protein C is rapidly and irreversibly inhibited. The site of copper inhibition has been shown to be primarily at the iron-sulphur centre of protein C with a secondary effect at the FAD centre when the copper(II):protein C ratio is high. Copper appears to bring about the inhibition of soluble MMO by interacting with protein C to disrupt the protein structure causing, firstly, the loss of the iron-sulphur centre, preventing the transfer of electrons from protein C to protein A, and secondly, the loss of FAD preventing the protein from accepting electrons from NADH. Inhibition and spectral data are provided to support this thesis. The inactivation of protein C is associated with the tight binding of four Cu atoms to each protein C molecule. These data extend our knowledge of how copper, which is known to have a key role in the cellular location of MMO, interacts with and rapidly and irreversibly inactivates the soluble form of this enzyme.
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PMID:Copper ions as inhibitors of protein C of soluble methane monooxygenase of Methylococcus capsulatus (Bath). 393 77

During biosynthesis, MHC class II molecules are diverted to endocytic compartments in which they bind antigenic peptides to be displayed on the surfaces of APC. For many Ags, the efficiency of class II presentation is enhanced by the intracellular association of class II with invariant chain (li), consistent with a role for newly synthesized class II molecules in Ag presentation. For a subset of Ags, however, efficient presentation does not require li. These Ags may also be bound by class II molecules en route to the cell surface. Alternatively, li-independent Ag presentation may utilize a pool of preexisting class II molecules that may gain access to endosomes following internalization from the cell surface. To examine the role of newly synthesized class II in the presentation of the li-independent Ag, RNase, we placed class II biosynthesis under the translational control of an iron response element. Chelation of iron from the media resulted in efficient diminution of class II synthesis and a marked decrease in the efficiency of RNase presentation. When compared with other cells expressing varying amounts of class II, we found that the ability to present RNase correlates with the level of class II biosynthesis and not with the level of class II surface expression. Because these cells internalize class II at a significant rate, we conclude that even in the absence of li, class II molecules can reach endocytic compartments containing antigenic peptides and they do so on their biosynthetic pathway.
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PMID:Invariant chain-independent antigen presentation depends primarily upon the pool of newly synthesized MHC class II molecules. 763 38

The purpose of the present study was to evaluate the nutritional status of children based on anthropometric measurements, biochemical indicators of protein energy malnutrition as well as hematological variables. The subjects were 93 10- to 12-year-old Bolivian boys: 12 HAHSES, 28 HALSES, 36 LALSES, and 17 LALSES (see Introduction to this Supplement). The overall nutritional status of the boys was evaluated by anthropometric indicators (weight for age [W/A], height for age [H bd, and weight for height [W/H]). The biochemical indicators included proteins total, albumin, prealbumin, orosomucoid and protein C-reactive (for MPE) as well as hematocrit (Ht), hemoglobin (Hb), serum iron, serum ferritin, and transferrin saturation (TS). The prevalence of growth retardation of LSES boys at HA as well as at LA was found to be high when the 3rd percentile was used as the cutoff point. The corresponding prealbumin levels were found to be lower in LSES than in HSES boys at both altitudes. The study shows that LSES boys at both altitudes have significantly lower prealbumin levels than HSES boys. The socioeconomic factor seems to be more critical for the nutritional status of prepubertal boys than altitude. The study also shows that all the boys had hematological parameters within normal range. The HA boys of both SES had higher hemoglobin concentration and hematocrits than the LA boys, a fact that is explained by high-altitude hypoxia. The hematological data do not provide evidence of malnutrition among the boys.
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PMID:Circulating proteins and iron status in blood as indicators of the nutritional status of 10- to 12-year-old Bolivian boys. 805 65

Erythropoietin (EPO) therapy in hemodialysis patients may be associated with an enhanced risk of vascular access and extracorporeal thrombosis. Assessment of blood coagulation and fibrinolysis was performed monthly on a group of 21 hemodialysis patients treated with EPO, and on four iron-deficient hemodialysis patients treated with iron dextran infusions alone. Seventeen of the EPO treated patients were also monitored after withdrawal of EPO to allow hemoglobin to fall to pre-EPO levels, and 16 of these patients during a second subsequent phase of EPO therapy with EPO administered using the alternative route (subcutaneous/intravenous) from the first phase of treatment. Ten untreated hemodialysis patients with intrinsically high hemoglobins were studied as controls. EPO was associated with significant increases in the endothelial product Factor VIII von Willebrand factor antigen (FVIIIvWFAg), and plasma fibrinogen, to levels comparable to those observed in the untreated control patients. Both FVIIIvWFAg and fibrinogen remained significantly elevated when EPO was withdrawn. Whole blood platelet aggregation (spontaneous, collagen, and ADP-induced) also increased following EPO, collagen and ADP-induced aggregation, increasing further when EPO was withdrawn. Transient but significant changes occurred in plasma measures of thrombin-antithrombin III complex, prostacyclin stimulating factor, and protein C during the first EPO treatment phase, and also thrombin-antithrombin III complex during the second treatment phase, all favoring a tendency to thrombosis. D-dimer increased significantly following EPO withdrawal. Erythrocyte deformability, and granulocyte aggregation did not change. There was no effect of route of EPO administration (subcutaneous or intravenous) or EPO dose on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of erythropoietin therapy and withdrawal on blood coagulation and fibrinolysis in hemodialysis patients. 835 60

Myosin binding protein C (MyBP-C) is a major myofibril-associated protein in cardiac muscle which is subject to reversible phosphorylation. Cardiac MyBP-C is a substrate in vivo and in vitro for cAMP-dependent protein kinase (PKA) and calcium/phospholipid-dependent protein kinase (PKC). Chicken cardiac MyBP-C was phosphorylated by PKA to 3.0 mol phosphate/mol and by PKC to 2.0 mol phosphate/mol. Tryptic phosphopeptides from MyBP-C were purified by successive iron iminodiacetate column chromatography and reversed-phase high-performance liquid chromatography. Three phosphopeptides purified from PKA-phosphorylated MyBP-C contained phosphoserine [T1, (RTS[P]LAGGGR) and T2, (KRDS[P]FLR)] or phosphothreonine (CT3, MT[P]SAFL). PKC phosphorylated two of the same sites (T1 and T2) as PKA and an additional site [T2a (TGTTYKPPS[P]YK)]. PKA phosphorylation sites corresponding to peptides T1, T2, and T3 were identified in the N-terminus of the cDNA deduced amino acid sequence (S265, S300, and T274, respectively). The PKC-specific site in peptide T2a was at position S1169. cDNA clones encoding rat cardiac MyBP-C were isolated, and the segment corresponding to PKA and major PKC phosphorylation sites was sequenced. Chicken cardiac MyBP-C has a threonine at position 274 (CT3), whereas rat cardiac MyBP-C has a serine at the corresponding position. Only chicken cardiac MyBP-C had a phosphorylatable residue at the position corresponding to S1169. All of the cardiac MyBP-C phosphorylation sites are absent in known sequences of skeletal muscle MyBP-C isoforms.
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PMID:Cardiac myosin-binding protein C (MyBP-C): identification of protein kinase A and protein kinase C phosphorylation sites. 978 45

We evaluated more than 450 patients with thrombophilia or iron overload for the presence of a factor V Leiden (R506Q), prothrombin G20210A, or HFE C282Y mutation using a standard method (polymerase chain reaction [PCR]-restriction fragment length polymorphism) and a comparative real-time PCR fluorescent resonance energy transfer (FRET) hybridization probe melting curve method. There was 100% concordance between the genotypes ascertained by the 2 methods (at each loci). In addition, phenotypic biochemical laboratory parameters measured on a subset of referred patients correlated with their respective genotypes. In the iron overload cohort, HFE C282Y homozygotes (n = 74) had significantly higher (P < .0001) transferrin saturation levels (74% +/- 25%) than did nonhomozygotes (n = 340; 51.4% +/- 28%), suggesting a genotype-dependent increase in body iron loads. In the thrombophilic cohort, the degree of activated protein C resistance (APCR), measured by a clotting time-based test, was associated significantly with the presence of 0 (n = 255; APCR = 2.59 +/- 0.26), 1 (n = 84; APCR = 1.61 +/- 0.13), or 2 (n = 5; APCR = 1.16 +/- 0.04) copies of the mutant factor V Leiden allele. As the fluorescent genotyping method required no postamplification manipulation, genotypes could be determined more quickly and with minimized risk of handling errors or amplicon contamination. In addition to these practical advantages, the FRET method is diagnostically accurate and clinically predictive of phenotypic, disease-associated manifestations.
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PMID:Real-time polymerase chain reaction with fluorescent hybridization probes for the detection of prevalent mutations causing common thrombophilic and iron overload phenotypes. 1124 1

We present the results on Anaemia Management in Fresenius Medical Care Spain dialysis centres as reported by EuCliD (European Clinical Database), evaluating a population of 4,426 patients treated in Spain during the year 2001. To analyse the erythropoietin dose and the haemoglobin levels we divided the population in two groups according to the time with dialysis treatment: patients treated less than six months and patients between six months, and four years on therapy. We compared our results with the evidence based recommendations Guidelines: the European Best Practice Guidelines (EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on 2,618 patients on dialysis in Spain carried out in the second half of the year 2000. We observed that 70% of the population reaches an haemoglobin value higher that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients. About the iron therapy, 86% of the patients received iron treatment and the administration route was intravenous in 93% of the population. The ferritin levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a transferrin saturation index (TSAT) below 20%. The erythropoieting resistance index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to rHu-Epo, according to different variables. It was observed that the following factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as administration route, the presence of hypoalbuminemia, increase of protein C reactive, Transferrin saturation below 20% and starting dialysis during the last six months.
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PMID:[Anemia management in haemodialysis. EuCliD database in Spain]. 1251 89


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