Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and alpha2-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and plasmin/alpha2-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
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PMID:Plasma proteolytic activity in liver transplant rejection. 1036 91

This study was performed to determine whether human urinary soluble thrombomodulin plays a role in liver ischemia-reperfusion injury. Liver ischemia was induced in two groups of dogs. Group 1 was exposed to 60 min ischemia, and group 2 was exposed to 60 min ischemia after preischemic administration of human urinary soluble thrombomodulin. In group 1, the thrombin-antithrombin complex and hyaluronic acid were significantly elevated after ischemia, compared with the preischemic values. While liver issue blood flow and the plasmin-alpha(2)-plasmin inhibitor complex significantly decreased, AST, ALT and m-AST dramatically increased after reperfusion. In group 2, the increase in the thrombin-antithrombin complex and hyaluronic acid was significantly suppressed, and AST, ALT and liver tissue blood flow significantly improved, compared with group 1. Histologically, in group 2, the hepatic tissue structure, including endothelial cells, was relatively intact. These findings suggest that administration of thrombomodulin inhibits endothelial cell injury and coagulopathy and offers protection from liver ischemia-reperfusion injury.
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PMID:Protective effect of human urinary thrombomodulin on ischemia- reperfusion injury in the canine liver. 1081 Feb 13

Thromboembolism is a serious complication after Fontan operation, which may be caused by alterations of the coagulation system. We therefore investigated pro- and anticoagulant factors in 20 patients aged 4 to 21 years, 4 to 63 months following total cavopulmonary connection. Furthermore we compared markers of thrombin activation and fibrinolysis and in vitro clotting and clot-lysis to age-matched healthy subjects. Compared to results of age-matched controls, the Fontan operated individuals had significant decreases in levels of protein C (0.88 U/ml in controls, 0.67 U/ml in patients; p <0.001) and protein S (1.05 in controls, 0.93 U/ml in patients; p <0.05). Moreover, half of the patients had high values of FVIII (>1.5 IU/ml), which are associated with an increased thrombotic risk. These changes may result in enhanced generation of thrombin and plasmin, indicated by our finding of increased thrombin-antithrombin III (TAT) and plasmin-antiplasmin (PAP) levels and a similar trend in prothrombin fragments F1+2. Clot lysis tests, global coagulation tests, red blood cell count, liver enzymes AST, ALT, but not GGT, were generally within the normal ranges.
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PMID:Hemostatic changes following the modified Fontan operation (total cavopulmonary connection). 1181 32

The medical records of 21 patients evaluated for mastocytosis and 2 patients seen for follow-up of known mastocytosis who underwent bilateral iliac crest aspirations and biopsies were reviewed retrospectively to determine whether mastocytosis could be confirmed in each of a patient's biopsy specimens. In 19 cases (83%), each biopsy specimen showed evidence of mastocytosis; however in 4 cases (17%), only 1 of 2 biopsy sites revealed mastocytosis. Compared with the 4 patients with only a unilateral positive biopsy result, the bilateral group had significantly higher urinary excretion of 11beta-prostaglandin F2alpha, higher serum tryptase levels, and higher serum calcitonin values, and a higher percentage had splenomegaly (37% [7/19] vs 0% [0/4]). The 2 groups could not be distinguished by the main initial symptom(s), presence of urticaria pigmentosa, or other laboratory findings (alkaline phosphatase, aspartate transaminase, or hemoglobin concentrations or total WBC, total eosinophil, or platelet counts). Bilateral biopsies might be useful for diagnosing early systemic mastocytosis or detecting minimal bone marrow involvement.
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PMID:Bone marrow biopsies for the diagnosis of systemic mastocytosis: is one biopsy sufficient? 1498 41

Plasminogen activator inhibitor type-1 (PAI-1) is the major negative regulator of the plasmin-dependent pericellular proteolytic cascade. PAI-1 gene expression is normally growth state regulated but frequently elevated in chronic fibroproliferative and neoplastic diseases affecting both stromal restructuring and cellular migratory activities. Kinetic modeling of cell cycle transit in synchronized human keratinocytes (HaCaT cells) indicated that PAI-1 transcription occurred early after serum stimulation of quiescent (G0) cells and prior to entry into a cycling G1 condition. PAI-1 repression (in G0) was associated with upstream stimulatory factor-1 (USF-1) occupancy of two consensus E box motifs (5'-CACGTG-3') at the PE1 and PE2 domains in the PF1 region (nucleotides -794 to -532) of the PAI-1 promoter. Chromatin immunoprecipitation (ChIP) analysis established that the PE1 and PE2 site E boxes were occupied by USF-1 in quiescent cells and by USF-2 in serum-activated, PAI-1-expressing keratinocytes. This reciprocal and growth state-dependent residence of USF family members (USF-1 vs. USF-2) at PE1/PE2 region chromatin characterized the G0 --> G1 transition period and the transcriptional status of the PAI-1 gene. A consensus E box motif was required for USF/E box interactions, as a CG --> AT substitution at the two central nucleotides inhibited formation of USF/probe complexes. The 5' flanking sites (AAT or AGAC) in the PE2 segment were not necessary for USF binding. USF recognition of the PE1/PE2 region E box sites required phosphorylation with several potential involved residues, including T153, maping to the USF-specific region (USR). A T153A substitution in USF-1 did not repress serum-induced PAI-1 expression whereas the T153D mutant was an effective suppressor. As anticipated from the ChIP results, transfection of wild-type USF-2 failed to inhibit PAI-1 induction. Collectively, these data suggest that USF family members are important regulators of PAI-1 gene control during serum-stimulated recruitment of quiescent human epithelial cells into the growth cycle.
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PMID:PAI-1 transcriptional regulation during the G0 --> G1 transition in human epidermal keratinocytes. 1662 40