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Biomedical subjects

A M Dosne

Publications and source records attributed to A M Dosne.

13 recordsLinked to original sources

Importance of plasminogen activator inhibitor type 1 (PAI-1) for preventing single chain urokinase plasminogen activator (scu-PA) conversion into two chain urokinase plasminogen activator (tcu-PA) in plasma in vitro.

We have studied the effects of PAI-1 on the conversion of scu-PA into tcu-PA in vitro in plasma containing or not a 125I-fibrin clot by determining tcu-PA activity on S2444. Two preparations of PAI-1 have been used, a fraction of medium conditioned with the monkey Vero cells (Vero-Prep), the antiurokinase activity of which is inhibited at 83% by anti PAI-1 IgG, or purified human PAI-1 from HT 1080 fibrosarcoma cells. Scu-PA purified from human kidney cells has been treated with diisopropylfluorophosphate before use. In plasma, conversion of scu-PA into the tc form is accelerated by addition of anti PAI-1 IgG. In plasma containing a clot, generation of tcu-PA, is considerably delayed after addition of the Vero-Prep or human PAI-1. Clot lysis is also decreased but to a lesser extent than it would be expected from the level of tcu-PA activity. Addition of anti PAI-1 antibodies shortens the lag phase before tcu-PA appears and moderatly accelerates clot lysis. These results demonstrate the importance of PAI-1 for the stability of scu-PA in plasma in vitro by delaying its conversion into tcu-PA.

Animals

[Vascular endothelium (author's transl)].

Studies during recent years have shown the importance of the vascular endothelium in several physiological and pathological circumstances. The culture of endothelial cells has permitted the direct study of endothelial functions. The endothelium is a selective barrier between blood and tissues: the molecules cross it, according to their size, either through the intercellular junctions or through the cells by pinocytotic vesicles. The permeability is modulated by vasomotor agents and modified during endothelial regeneration, especially for the lipids. The endothelium plays a prominent part in the maintenance of the blood flow through its nonthrombogenic properties. It metabolizes circulating thrombogenic substances (arachidonic acid, adenosine diphosphate) and produces potent antiaggregating agents (prostacyclin and adenosine). It may also release a plasminogen activator promoting thrombolysis. The endothelial cells contribute to the formation of the basement membrane by synthesizing collagen and fibronectin, which are involved in platelet adhesion and aggregation to exposed subendothelium. On the other hand, the endothelium has a modulating influence on the local blood flow by producing vasoconstrictors (angiotensin II and III) and vasodilating agents (adenosine and prostacyclin). It is not necessary to elucidate the coordination of these functions and their relationship to the endothelial disorders in vascular diseases.

Actins

[Vascular subendothehlium: structure and functions (author's transl)].

Two subendothelial structures, glomerular basement membrane and arterial subendothelium, were compared regarding their biochemistry and ultrastructure and their role in physiology and pathology. Filtration function of the glomerular basement membrane can be related to the presence of three layers which are superimposed on each other and which differ regarding the orientation and density of the microfibrils. The arterial subendothelium which is a mixture of amorphous material, microfibrilis, elastin and collagen, with a still unknown orientation of these components, limits the transport of many blood molecules and reinforces the endothelial barrier. A striking difference is observed in the thrombogenicity of these two structures, especially in their reactivity towards platelets. This can be related to the presence of collagen IV in the glomerular basement membrane and of collagen III in the arterial subendothelium: in both cases adhesion of platelets can be observed. The presence of platelet aggregates on the subendothelial surface may also be seen. This is probably due to the presence of collagen III which is known to be able to induce the platelet release reaction and thereby promotes aggregation.

Animals