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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-2-antiplasmin, a major inhibitor of fibrinolysis, is synthesized in the liver and occurs in blood in two molecular forms: a very active plasminogen-binding (PB) form and a less active nonplasminogen-binding (NPB) form. This study investigates the origin and mutual relationship of these two forms in vivo and in vitro. Despite wide variation in plasma concentration of the inhibitor (16% to 138%), the ratio between the two forms in vivo was found to be, in the main, constant among healthy volunteers, heterozygotes for a congenital deficiency of alpha-2-antiplasmin, and patients with a stable liver cirrhosis: PB/NPB = 2.41 +/- 0.34 (SD). Resynthesis after depletion or increased synthesis in the acute-phase reaction showed a specific increase of the PB form of the molecule in blood after discontinuation of L-asparaginase or streptokinase therapy and after myocardial infarction. In vitro studies demonstrated that only the PB form was present after one day in the culture medium of the human cell line Hep G2, while the NPB form appeared after 11 days. Clearance after inhibition of synthesis by L-asparaginase therapy revealed a more rapid decrease in the PB form relative to the NPB form in blood, demonstrated by a change in the PB-NPB ratio from 2.86 +/- 0.55 to 1.74 +/- 0.24 (mean of 6, SD). An apparently spontaneous first order conversion from the PB to NPB form, with an apparent half-life of about eight days, was demonstrated at 37 degrees C in plasma and serum in vitro. The conversion was found to be temperature dependent and uninfluenced by the fibrinolytic components fibrinogen, fibrin, and plasminogen. Additions of a variety of enzymes or inhibitors did not interfere with the process. These results demonstrate that the PB form of alpha-2-antiplasmin is produced by the liver and that the NPB form is formed in the circulation.
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PMID:The mutual relationship between the two molecular forms of the major fibrinolysis inhibitor alpha-2-antiplasmin in blood. 241 96

Tetranectin is a tetrameric protein that binds to kringle 4 of plasminogen. Increase of electrophoretic mobility of the otherwise slowly migrating tetranectin in the presence of ethylenediaminetetraacetate was used to develop a reproducible electroimmunoassay to quantify plasma levels. Plasma levels in normals were found within narrow limits of 100 +/- 16 (SD)%, (100% = 0.15 mumol/l). There was no difference between males and females, smokers and non-smokers, and there were no significant changes with age from 20 to 49 years. Patients with severe liver cirrhosis showed a large variation in plasma tetranectin levels but no systematic or average reduction, in contrast to strong reductions in plasma levels of other proteins. Patients treated with L-asparaginase showed a gradual reduction in time in plasma levels of various proteins, though tetranectin showed no significant reduction. It is concluded that tetranectin can be assayed reproducibly in plasma and has a well regulated plasma level. This level is not sensitive to conditions with reductions in synthesis of many proteins, such as during cirrhosis of the liver and during L-asparaginase therapy. The reductions in plasma levels during the use of oral contraceptives and pregnancy indicate involvement of sex steroids in the metabolism of tetranectin.
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PMID:Quantitation of plasma levels of tetranectin--effects of oral contraceptives, pregnancy, treatment with L-asparaginase and liver cirrhosis. 281 26

An 11-year-old boy was diagnosed as having acute lymphoblastic leukemia (ALL, L1) in 1987 and underwent treatment with an ALL high-risk protocol (prednisolone, vincristine (VCR), daunorubicin, 1-asparaginase), which resulted in complete remission. In 1990 he developed chronic hepatitis C and received interferon therapy. In December 1994, ALL recurred, and the patient was treated with VCR. He subsequently developed severe hemolysis (Hb 12.5 g/dl-->6.8 g/dl) with increases of indirect bilirubin, AST, and LDH. Furthermore, symptoms resembling a syndrome of inappropriate secretion of ADH (SIADH) and DIC developed. Upon incubation of the patient's red blood cells with VCR in vitro, extreme deformity of the cells was observed. These findings suggested that splenomegaly, due to liver cirrhosis which had developed rapidly from chronic hepatitis C while the patient was in an immunosuppressed state induced by anticancer drugs, had trapped the deformed red blood cells and resulted in severe hemolysis. The patient died on the 165th day after admission due to liver failure.
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PMID:[Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis]. 1119 45