Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this pilot study was to determine the effect of recombinant hirudin (r-hirudin) on coagulopathy and the relationship between concentrations of thrombin-antithrombin III (ATIII) complex (TAT) and thrombin-hirudin complex (THC) in patients with disseminated intravascular coagulation (DIC). Five patients with haematological malignancy associated with DIC were studied. r-Hirudin was administered by continuous intravenous infusion at a dose of 0.005 mg/kg/h for 4-9 days to each patient. Fibrin/fibrinogen degradation products (FDP), D-dimer, TAT and plasmin-alpha 2 antiplasmin complex (PAP) concentrations decreased after treatment with r-hirudin in four patients studied. However, in one patient, serum creatinine increased to 1.7 mg/dl and aPTT was prolonged to 74.4s. Statistical analysis disclosed significant positive correlations between plasma concentrations of hirudin and THC, and between concentrations of THC and TAT. The concentrations of THC were much higher than those of TAT. In conclusion, these findings indicate that r-hirudin more strongly inhibited thrombin than did ATIII without heparin, and that administration of r-hirudin to renal insufficiency required individual adjustment of dosage. The present findings also suggest that r-hirudin can be considered a new agent for the treatment of DIC.
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PMID:Recombinant hirudin for the treatment of disseminated intravascular coagulation in patients with haematological malignancy. 754 Aug 78

Propionic acidaemia (PCCD) or deficiency of propionyl-CoA carboxylase (PCC) is one of the most common organic acidaemias. Recent studies have suggested that this disease can cause somatic or cognitive deterioration even in patients without ketosis or metabolic acidosis, or in cases with unusually late onset. This suggests that for this disease a sensitive yet practical screening procedure is required to achieve early treatment. We conducted a pilot study of gas chromatographic-mass spectrometric screening of 12,000 newborns for PCCD using eluates from dried filter-paper urine collected at 4-7 days of age. Methylcitrate (MC) was targeted for PCCD. For bulk screening, 2-hydroxyundecanoate was used as internal standard; for quantification, stable-isotope-labelled MC was used. Urease pretreatment without fractionation allowed satisfactory recovery and reproducibility of the highly polar MC. We detected an asymptomatic male infant with distinctly elevated MC: the creatinine-corrected level relative to 2-hydroxyundecanoate was 4.8 SD above the normal mean. The MC concentration calculated using the stable-isotope-labelled internal standard was 70.6 mmol/mol creatinine 14.7 SD above the normal mean of 3.70. Parallel analysis of the dried blood spot at 4 days of age by tandem MS showed only borderline elevation of propionylcarnitine. The activity of PCC in lymphocytes was 7% of control. Gene analysis revealed that a single missense mutation, TAT to TGT, resulting in Y435C in the beta chain was present in a homozygous form. Dietary treatment including carnitine supplementation decreased this infant's MC level and to date (at 13 months of age), he shows no neurological or somatic abnormalities.
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PMID:Gas chromatographic-mass spectrometric newborn screening for propionic acidaemia by targeting methylcitrate in dried filter-paper urine samples. 1211 33

Kidney transplant recipients are not only prone to dyslipidemia but also have a high risk of cardiovascular death. Impairment of the fibrinolytic system is thought to be one factor playing a role in development of thrombotic complications. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations and activities in renal transplant recipients stratified based upon serum cholesterol values above 220 mg/dL or below 200 mg/dL. The groups did not differ regarding age, creatinine clearance, BMI, time after transplantation, albumin, fibrinogen, thrombomodulin, or PAP. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex TAT, prothrombin fragments 1 + 2); TAFI activator; thrombomodulin (TM), catalyzer of TAFI activation; and the degree of plasmin generation (plasmin-antiplasmin complex PAP) using commercially available kits. In patients with hyperlipidemia significantly higher TAFI concentrations and activities may contribute to prolonged ECLT and lowered fibrinolytic activity index (FAI). Increased levels of F1 + 2 and TAT were observed in hypercholesterolemic patients, indicating enhanced thrombin generation. Elevated TAFI concentration, and activities and enhanced thrombin generation observed in hypercholesterolemic kidney transplant recipients may contribute to hypofibrinolysis and progression of atherosclerosis in this group of patients.
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PMID:Thrombin-activatable fibrinolysis inhibitor in kidney transplant recipient with dyslipidemia. 1452 94

Kidney transplant recipients are prone to hypertension, dyslipidemia, and cardiovascular death. Hypertension is associated with hemostatic abnormalities. Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein that links coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations in renal transplant recipients in relation to blood pressure. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex [TAT], prothrombin fragments 1+2 [F1+2]), thrombomodulin (TM), and the degree of plasmin generation (plasmin-antiplasmin complex [PAP]) using commercially available kits. The studies were performed on 86 renal allograft recipients (48 women, 38 men) at age range 26 to 73 years. The immunosuppressive regimen consisted of cyclosporine (CsA), prednisone, and azathioprine (n = 58) or mycophenolate mofetil (MMF; n = 28). All patients maintained sufficient and stable graft function, showing no clinical signs of rejection. In patients with hypertension (n = 68), we observed significantly higher concentrations of TAFI and of markers of thrombin generation (F1+2, TAT), and of thrombomodulin with significantly prolonged euglobulin clot lysis time (ECLT), which reflects overall fibrinolytic activity and lower fibrinolytic activity index (FAI). Both groups did not differ with respect to age, creatinine clearance, body mass index, time after transplantation, albumin, fibrinogen, and PAP. Diastolic blood pressure correlated significantly with TAFI concentrations, uric acid, and prednisone dose, whereas systolic blood pressure correlated with urea, uric acid, creatinine clearance, and MCV. Elevated TAFI concentrations and enhanced thrombin generation in hypertensive kidney transplant recipients may contribute to the hypofibrinolysis and progressive atherosclerosis in this population. Blood pressure was related to kidney function, maintenance prednisone dose, and TAFI concentration.
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PMID:Thrombin activatable fibrinolysis inhibitor in hypertensive kidney transplant recipients. 1650 76

To meet the increased clinical demands of our hospital expansion, improve quality, and reduce costs, our tertiary care, pediatric core laboratory used the Toyota Production System lean processing to reorganize our 24-hour, 7 d/wk core laboratory. A 4-month, consultant-driven process removed waste, led to a physical reset of the space to match the work flow, and developed a work cell for our random access analyzers. In addition, visual controls, single piece flow, standard work, and "5S" were instituted. The new design met our goals as reflected by achieving and maintaining improved turnaround time (TAT; mean for creatinine reduced from 54 to 23 minutes) with increased testing volume (20%), monetary savings (4 full-time equivalents), decreased variability in TAT, and better space utilization (25% gain). The project had the unanticipated consequence of eliminating STAT testing because our in-laboratory TAT for routine testing was less than our prior STAT turnaround goal. The viability of this approach is demonstrated by sustained gains and further PDCA (Plan, Do, Check, Act) improvements during the 4 years after completion of the project.
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PMID:Application of the Toyota Production System improves core laboratory operations. 2002 55