Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the presence of added Ca2+, and purified. We found that,...

The metabolism in vitro of human low-density lipoprotein by the human hepatoma cell line Hep G2

The human hepatoma cell line Hep G2 was studied with respect to metabolism of human low-density lipoprotein (LDL). The Hep G2 cells bind, take up and degrade human LDL with a high-affinity saturable and with a low-affinity non-saturable component. The high-affinity binding possesses a K(D) of 25 nM-LDL and a maximal amount of binding of about 70...

Identification of a reversible inhibitor of plasminogen activators in blood plasma

Inhibition of tissue-type plasminogen activator (t-PA) by pooled plasma could be ascribed for only 60% to the endothelial cell type PA inhibitor. The residual inhibition is ascribed to a so-far undescribed plasma component present at 0.2 nmol/l. This component shows reversible binding to t-PA with an apparent K(i) of 10 pmol/l (does not hinder t...

Differences in cytochrome P450-mediated biotransformation of 1,2- dichlorobenzene by rat and man: Implications for human risk assessment

The oxidative biotransformation of 1, 2-dichlorobenzene (1, 2-DCB) was investigated using hepatic microsomes from male Wistar, Fischer-344 and Sprague-Dawley (SD) rats, phenobarbital (PB)- and isoniazid (ISO) pretreated male Wistar rats and from man. In addition, microsomes from cell lines selectively expressing one cytochrome P450 (P4502E1, 1A1...

Concentration changes during venous occlusion of proteins with affinity for extracellular matrix in insulin-dependent diabetes mellitus A sign of vascular damage in patients with diabetic nephropathy?

Objective: To investigate protein concentration changes during venous occlusion of proteins with reported affinity for extracellular matrix (plasminogen activator inhibitor type 1, antithrombin III, fibronectin and von Willebrand factor) in comparison with proteins with no reported affinity (albumin, tissue-type plasminogen activator,...

IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due...

Clot penetration and fibrin binding of amediplase, a chimeric plasminogen activator (K2tu-PA)

Amediplase (K2tu-PA) is a hybrid plasminogen activator, consisting of the kringle 2 domain of alteplase and the protease domain of urokinase. The objective of this study was to determine the in vitro clot penetration of amediplase in relation to its fibrin binding and to compare the properties with those of alteplase. The clot lysis activity of...

Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans

Objective: The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is ...

Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells

Background: Milk products are a potential matrix for fortification with synthetic folic acid or natural 5-methyltetrahydrofolate (5-CH 3-H4folate) to enhance the daily folate intake. In milk, folate occurs bound to folatebinding proteins (FBP). Our previous studies with an in vitro gastrointestinal model showed that 70% of the initial FBP...

Toxicokinetics and metabolism

Lupine allergy: Not simply cross-reactivity with peanut or soy

Background: Reports of lupine allergy are increasing as its use in food products increases. Lupine allergy might be the consequence of cross-reactivity after sensitization to peanut or other legumes or de novo sensitization. Lupine allergens have not been completely characterized. Objectives: We sought to identify allergens associated with...