Search PubMed⌕ Search

Biomedical subjects

L Capron

Publications and source records attributed to L Capron.

At least 73 records · Page 4Linked to original sources
PubMed1990

A plasma clot lysis assay based on the release of fibrin degradation products: application to the diagnosis of hypofibrinolytic states.

Using a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombophlebitis, 3 arterial occlusions of lower limbs). tPA and PAI-1 concentrations were determined using ELISA assays; the post-occlusion values were corrected for haemoconcentration. The increase in tPA during VO was correlated with haemoconcentration (r = 0.74), but 3 patients had ineffective VO (less than 2% increase in proteins). The fibrinolytic response to VO was evaluated using the shortening of the time necessary for the release of 200 micrograms of fibrin degradation products per mg of fibrinogen (delta T 200). Two among the 27 patients with effective VO were bad responders with a delta T 200 less than 3 h (whereas all the others had delta T 200 greater than 10 h). These patients had respectively a deficient tPA release (delta tPA = 1 ng/ml) and an elevated PAI-1 level at rest (33 ng/ml). Several other patients were bad responders in terms of tPA release or of shortening of the euglobulin clot lysis time but they had a normal delta T 200. This plasma clot test reflects the ability of free tPA to bind to fibrin (the amount of which depends on the level of tPA and PAI-1), and may be useful in the diagnosis of a hypofibrinolytic state.

Adult↗
PubMed1990

[Up-date on atherosclerosis].

The major steps of the pathogenesis of atherosclerosis are now well defined. Efforts are still required to better characterize: 1. the cellular mechanisms of atherogenesis, without ignoring the limitations of the available experimental models; 2. the complications of human atherosclerosis, ie the events (ulceration, thrombosis) that provoke ischaemic manifestations. Four short reviews on topics of special interest follow: proliferation of arterial smooth muscle cells; interactions of blood cells (platelets, leukocytes) with the arterial wall; lipoproteins in the genesis of foam cells; recent progresses in genetic epidemiology of cardiovascular diseases.

Animals↗
PubMed1989

[Pathogenesis of atherosclerosis: an update on the three main theories].

The causes and mechanisms of atherosclerosis remain incompletely understood. Almost all the present investigations are still connected with one of the main three historical theories of atherosclerosis: 1) the incrustation theory, as developed by von Rokitansky, has now led to the many studies on the roles of thrombosis and platelets; 2) the irritation theory, as opposed to the preceding one by Virchow and his school, is reviving through the rediscovery that leukocytes are present in the plaques, and that atherosclerosis (Virchow's endarteritis chronica deformans sive nodosa) has the features of a chronic inflammatory reaction; 3) the lipid infiltration theory, as initiated by the experiments of Anitschkov and Chalatov in rabbits fed a cholesterol enriched diet, motivates the huge mass of studies devoted to plasma lipids and their cellular metabolism. This article provides a brief update on each of these three complementary approaches of atherosclerosis.

Animals↗
PubMed1989

[Participation of platelets in the progression of atherosclerosis].

The role of platelets in the early steps of atherosclerogenesis is controversial, but it is well established that platelets play a prominent part in arterial thrombosis, the leading event in the progression of atherosclerosis. Ulceration of the plaque breaks the endothelial cover, and induces blood to interact with the deeper components of the lesion, which leads to adhesion, activation and aggregation of platelets at the intimal breach. The resulting clump of platelets becomes a thrombus by further platelet accumulation and the addition of fibrin (through the triggering of the coagulation cascade). The thrombus has three possible fates. 1. It can grow by addition of successive layers of platelet, fibrin, white and red blood cells, until it eventually occludes the arterial lumen, often provoking an ischaemic event (such as a myocardial infarction). 2. At any time of its growth, the thrombus can be dislodged in whole or in part to cause arterial embolism. 3. The thrombotic material may become overgrown by endothelium and incorporated into the intima, becoming part of the atherosclerotic lesion and strongly contributing to the increase of its sclerotic as well as atheromatous (lipid) mass. Although the mechanisms of ulceration remain unclear, the resulting platelet activation leads to mural thrombosis and greatly contributes to the progression and complications of atherosclerosis. Available antiplatelet agents interfere favourably with the atherosclerotic process, but more efficient drugs will be designed when we better understand the mechanisms of ulceration and the influences that modulate the growth and fate of arterial thrombi.

Animals↗
PubMed1989

Influence of applied stress on mitotic response of arteries to injury with a balloon catheter: quantitative study in rat thoracic aorta.

Proliferation of arterial smooth muscle cells is an important feature of atherosclerosis, and a well documented reaction to intimal injury. To assess the influence of the intensity of injury to rat thoracic aorta, we studied the effects of a soft or hard friction with a moderately or tightly inflated balloon catheter at 2, 14 and 30 d after operation. As compared with soft injury, hard injury (1) strongly enhanced the proliferating response of the aortic intima and media (median incorporation of tritiated thymidine into deoxyribonucleic acid on day 2 increase 2.8-fold, 95% confidence interval 2.3-3.3; median deoxyribonucleic acid content on day 14; 102.1 v 72.1 micrograms); (2) markedly delayed endothelial regeneration (median percentage of intimal area stained by Evans blue on day 14: 33.1 v 0.6%). On day 2, transmission and scanning electron microscopy showed that endothelial denudation was complete after a hard injury, but only partial after a soft one. However, macroscopic staining of the intima with Evans blue was complete in both instances. The extent of endothelial denudation appears to be a major determinant of the mitotic reaction of arteries to injury. In the experimental search for drugs to reduce muscular proliferation (of potential value in the prevention of restenosis after percutaneous transluminal angioplasty), endothelial injury with balloon catheters should be carefully standardised, and applied "blindly" to afford valid comparisons between treated and control groups of animals.

Animals↗
PubMed1989

[Inflammation and atherosclerosis].

Inflammation is the reaction of a vascularized living tissue to local injury. Acute and chronic inflammation result from complex interactions between leukocytes, mesenchymal cells and various components of plasma. The aim of inflammation is reparation, but persisting chronic inflammation is a source of disease. Atherosclerosis can be viewed as an impairment of the normal relationships between blood and arterial wall. As proposed by pathologists of the last century, inflammation may provide a physiopathologic frame for atherosclerosis. Human atherosclerotic lesions at any step of their evolution, as well as the pathogenic models that have been developed to explain atherogenesis, share many features of an inflammatory reaction of arterial intima: increased penetration of plasma components, proliferation of smooth muscle cells, infiltration by monocytes/macrophages and by lymphocytes, building up of a sclerotic extracellular matrix and of a rich neovascularization. The inflammatory model neither contradicts nor jeopardizes the established knowledge on the roles of lipids and thrombosis in atherosclerosis. Rather, introducing the numerous cellular and molecular mediators of inflammation into the pathogenesis of atherosclerosis widens our field of investigations, and may open new avenues for prevention and treatment. There remains the major question of identifying the cause(s) which initiate(s) and perpetuate(s) arterial inflammation that lead to complicated atherosclerosis with ischemic manifestations.

Arteriosclerosis↗
PubMed1988

Antithrombin III Avranches, a new variant with defective serine-protease inhibition--comparison with antithrombin III Charleville.

A decreased plasma antithrombin activity in presence or in absence of heparin was discovered in a 47-year-old patient presenting with recurrent venous thromboembolism. The immunoreactive material (AT III-IR) was normal. The same biological abnormalities were found in two relatives of the patient, leading to the diagnosis of hereditary qualitative AT III deficiency. The propositus' AT III was coeluted with normal AT III from an heparin-sepharose column. An additional step of ion-exchange chromatography on a Mono Q column using a FPLC system (Pharmacia, St-Quentin en Yvelines, France) allowed the purification of a protein which was homogenous in SDS-10% polyacrylamide electrophoresis gel (PAGE). AT III purified from propositus' plasma, normal plasma and the plasma of the patient known to have an AT III variant with defective protease binding (AT III Charleville) were compared. The specific activities measured as heparin cofactor antithrombin or factor Xa inhibition in absence of heparin were decreased to half the normal value. Kinetic studies confirmed a decreased rate of thrombin inhibition for both abnormal AT III preparations. SDS-PAGE experiments performed in purified system and immunoblots obtained from plasma showed that the two variants have different behaviour: in the case of AT III Charleville thrombin induced an apparent 5 k delta increase in molecular mass, probably due to a conformational change. AT III Avranches did not form stoechiometric complexes with thrombin, but was unmodified by the protease.

Antithrombin III↗
PubMed1988

[New concepts of atherogenesis].

The main advances since 1980 in our understanding of atherosclerosis can be summarised under four headings. 1) The migration and proliferation of smooth muscle cells from the media into the intima are key-events of atherogenesis, and probably also of restenosis following percutaneous transluminal coronary angioplasty. The experimental study of their regulations, especially looking for inhibitors, has therefore gained increased interest as it may provide original approaches to the prevention of post-angioplasty restenosis. 2) The histiocytes/macrophages, derived from blood monocytes, also take a major part in the initiation of atherosclerotic lesions. An intensive research activity is now being devoted to elucidating the many facets of their participation in atherogenesis. 3) Brown and Goldstein's discoveries have explained the biochemical mechanisms of the increased plasma low-density lipoprotein (LDL) concentration found in familial hypercholesterolemia (type IIa), although they did not completely solve the enigma of lipid deposition in the arterial wall. The metabolic handling of modified LDLs appears to be crucial to the foamy transformation of macrophages and, possibly, of smooth muscle cells. 4) Risk factors identified by epidemiology are usually held responsible for atherosclerosis. Yet this causal interpretation is not entirely satisfactory, and alternative or complementary hypotheses are being but forward. Among them, the most consistent submits that a viral aggression of the arterial wall is involved in the genesis and progression of atherosclerosis.

Angioplasty, Balloon↗
PubMed1988

Association of inherited dysfibrinogenaemia and protein C deficiency in two unrelated families.

An inherited association of dysfibrinogenaemia and protein C deficiency was found in three members of the same family. The propositus was a 48-year-old man who suffered from severe and rapidly complicated atherosclerosis of the aorta and lower limbs arteries, which perhaps suggests that the association of these two molecular abnormalities may have enhanced the thrombotic process. The abnormal fibrinogen had a reduced ability to bind thrombin which may be thrombogenic. We found the same inherited association of dysfibrinogenaemia and protein C deficiency in a patient with venous thrombosis. The functional abnormality of the fibrinogen, which could have been responsible for thrombosis, was delayed proteolysis by plasmin. Not only fibrinogen, but also fibrin clots were resistant to plasmic degradation. These observations raise two questions: (1) Is the association of a protein C deficiency with a dysfibrinogenaemia fortuitous or the result of a common mechanism? (2) Is there a link between an increased thrombotic tendency and either both of the defects of haemostasis that we have found, or only one of them?

Adult↗
PubMed1987

Antithrombin III and heparin cofactor II in patients with chronic renal failure undergoing regular hemodialysis.

Heparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean +/- 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p less than 0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p less than 0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p less than 0.01) whereas HC II increased slightly but significantly (p less than 0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.

Adult↗
PubMed1987

An abnormal antithrombin III (AT III) with low heparin affinity: AT III Clichy.

We have identified an inherited qualitative deficiency of antithrombin III (AT III) in a family with apparently no increased incidence of venous thrombosis. Plasma antithrombin and anti-Xa activities were normal, but the interaction with heparin, heparan sulphate and low molecular weight heparin was uniformly decreased. An immunoblotting technique performed in plasma showed normal complex formation with thrombin. By using heparin-Sepharose affinity chromatography and crossed immunoelectrophoresis, the variant could be separated: at least two fractions of low affinity AT III were obtained. A minor one had no antiprotease activity; the other one was further purified to homogeneity and found to have normal specific activity in absence of heparin and a 50% decreased activity in presence of heparin. We propose to call this new variant AT III Clichy.

Adult↗