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Biomedical subjects

D Collen

Publications and source records attributed to D Collen.

At least 649 records · Page 36Linked to original sources
PubMed1978

Neoantigenic expression in enzyme-inhibitor complexes. A means to demonstrate activation of enzyme systems.

Human thrombin-antithrombin III and plasmin-antiplasmin, two enzyme-inhibitor complexes composed of four different molecules, contain antigenic structures not present in the parent molecules, which can be directly quantitated in plasma with the use of non-cross-reacting antisera. It is anticipated that this neonatigenic expression is a more general phenomenon, which could provide a simple means of measuring activation of enzyme systems in biological fluids.

Antigen-Antibody Reactions↗
PubMed1978

On the kinetics of the reaction between human antiplasmin and a low-molecular-weight form of plasmin.

The reaction between antiplasmin (A) and a low-molecular-weight form of plasmin (P) proceeds in at least two steps: a fast reversible second-order reaction followed by a slower irreversible first-order transition, and may be represented by: P +A k1 in equilibrium k-1 PA k2 leads to PA'. The low-Mr plasmin, which is obtained by limited elastase digestion, is composed of an intact B chain and a small A chain lacking the lysine-binding sites. The k1 of the reaction is (6.5 +/- 0.5) x 10(5) M-1 s-1 which is 30--60 times smaller than that for normal plasmin and antiplasmin. The dissociation constant of the first step is 1.9 x 10(-9) M which is 10 times higher than for normal plasmin and antiplasmin. The rate constant of the second step is (4.2 +/- 0.2) x 10(-3) s-1 for both normal and low-Mr plasmin. Low Mr plasmin which has substrate bound to its active site does not react or reacts only very slowly with antiplasmin. The reaction rate, however, is only slightly influenced by 6-aminohexanoic acid in concentrations up to 1 mM which decrease the reaction rate of normal plasmin approximately 50-fold. The findings further indicate that the lysine-binding site(s) of plasmin are of great importance for the rate of its reaction with antiplasmin.

Binding Sites↗
PubMed1978

Inhibition of plasmin by antithrombin-heparin complex. II. During thrombolytic therapy in man.

The role of antithrombin as an inhibitor of plasmin in the presence and absence of heparin was studied during thrombolytic therapy in 12 patients with vascular occlusive disease. The extent of plasmin-antithrombin-(heparin) complex formation was studied by intravenous injection of iodine-labelled antithrombin (5-20 muCi) and quantitation of the amount of antithrombin bound to plasmin. In the absence of heparin, less than 0.8% of the labelled antithrombin was recovered in the plasmin-antithrombin complex but between 1.2 and 4.8% following injection of 5000 iu of heparin. Thus only between 3 and 11% of the in vivo formed plasmin is neutralized by antithrombin-heparin complex. Repeated activation of the fibrinolytic system resulted in a shortening of the plasma radioactivity half-life of labelled antithrombin from 2.45 to 2.03 d in the absence of heparin (three patients), and from 3.13 to 2.35 d following heparin administration (two patients). This increased turnover does not result in a decrease of the plasma antithrombin level.

Adult↗
PubMed1978

Turnover of radiolabelled plasminogen and prothrombin in cirrhosis of the liver.

The turnover of purified radiolabelled plasminogen was studied in four patients with cirrhosis of the liver, and that of radiolabelled prothrombin in six patients with cirrhosis of the liver. The cirrhotic patients showed an increased fractional catabolic rate and a decreased synthetic rate, resulting in subnormal plasma levels of plasminogen and prothrombin. The plasma concentration of the two proteins correlated with the synthetic rate, but not with the fractional catabolic rate. Heparin infusion prolonged the shortened half-life of plasminogen in two cirrhotics from 1.25 to 2.10 days and from 1.45 to 1.90 days, and the half-life of prothrombin in three cirrhotics from 2.25 to 2.70 days, from 2.35 to 2.80 days and from 2.40 to 3.70 days. These results indicate that the abnormal turnover of labelled plasminogen and prothrombin in cirrhosis of the liver is due to two mechanisms; increased breakdown, reversible by heparin administration, and impaired synthesis. The decreased plasma levels are, however, mainly caused by decreased synthesis.

Humans↗
PubMed1978

Sensitivity and precision of activated partial thromboplastin time (APTT) methods. A multicenter study.

The Activated Partial Thromboplastin Time (APTT) test, Cephotest, was compared to other APTT methods in current use in 4 specialized coagulation laboratories. In 3 of 4 laboratories, the sensitivity of Cephotest was superior (P less than 0.001) to that of the local APTT method. There was no statistically significant difference between the APTT methods with regard to precision of repetitive testing. In each laboratory, the normal range of Cephotest was estimated on freshly collected plasma samples from healthy subjects. A mean value between 28.8 and 35.8 s, with a standard deviation of 1.1-3.3 s, was obtained. It is concluded that the composition of the APTT method if of importance for the sensitivity of this test, but does not influence the precision of repetitive testing to a significant degree. The use of a standardized reagent facilitates comparison of the results obtained with the APTT method from one laboratory to another.

Blood Coagulation Tests↗
PubMed1978

Fast-acting plasmin inhibitor in human plasma.

The fast-acting and physiologically most important inhibitor of plasmin in human plasma is a recently discovered and purified alpha 2-glycoprotein with a molecular weight of 65,000-70,000 daltons occurring at a concentration of 1 muM. The inhibitor rapidly forms a completely inactive 1:1 stoichometric complex with plasmin through reaction with the B chain (light chain) of the enzyme, which contains the active center. It also reacts with trypsin and very slowly with urokinase and with some other enzymes in purified systems, but its role in vivo as an inhibitor of proteases other than plasmin seems negligible. Antiplasmin is the only plasma protein that can inhibit the fibrinolysis associated with transformed or malignant cells. The plasmin-antiplasmin complex contains neoantigenic structures not present in the parent molecules that may form the basis of immunochemical methods for detecting activation of the fibrinolvtic system in blood.

Cell Transformation, Neoplastic↗