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Biomedical subjects

M Moczar

Publications and source records attributed to M Moczar.

100 records · Page 6Linked to original sources

Deterioration of bioprosthetic heart valves.

The aim of this study was to detect biologic factors in the structural deterioration of bioprosthetic heart valves. Prostheses were removed from patients after 4-8 years of implantation and submitted to biochemical and morphologic assays. Successive staining of biologic sections revealed colocalization of lipids and glycosaminoglycans underneath calcifications in the disintegrated extracellular matrix. On biochemical assays, the amidolysis of synthetic peptide substrates indicated thrombin, plasmin, and tissue plasminogen activator activities in the nonhemocompatible leaflets; 0.15 mol NaCl, 0.05 mol Tris, and 5 mmol CaCl2 extracts from the prostheses cleaved the peptide substrate for collagenase and lysed gelatin gels. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate disclosed the presence of low molecular mass polypeptides in extracts of the deteriorated prostheses. The detection of plasmin and collagenolytic enzyme(s), and the known broad proteolytic activity of plasmin, may point to the role of activation of the fibrinolytic system in the proteolytic degradation of bioprosthetic valves.

Animals↗

Complement activation is involved in the structural deterioration of bovine pericardial bioprosthetic heart valves.

Disintegrated collagen fibers surrounded with protein deposits are a morphologic feature in torn, folded, and disrupted cusps of pericardial prostheses explanted for clinical dysfunction. New technologies for valve bioprostheses with improved durability require further investigation of molecular mechanisms initiating the deterioration of bioprosthetic valves. The authors' aim was to obtain experimental evidence of biologic factors contributing to the degradation of the bioprosthetic matrix. Clinically failed Mitroflow (22), Hancock (3), Ionescu-Shiley (2), and Sorin (1) valves were explanted after 69-170 months. Non calcific deterioration of the prosthetic matrix was studied with labeled antibodies to plasma proteins and cells. IgG, and complement proteins C1q, C3, and C4 were accumulated close to dissociated collagen bundles (26/28) throughout the prostheses. Fibrin was identified on the cuspal surface and in the deep disrupted areas. The fibrin peptides and proteolytic breakdown products of the complement components, the latter consistent with complement activation and chemotaxis for monocytes, were shown by immunoenzymic assay on Western blots from the valve extracts. The complement activation triggered by the IgG aggregates generates bioactive peptide signals that can activate macrophages (22/28) and neutrophil granulocyte elastase (22/24) able to cooperate with the mechanical stress in the breakdown of the chemically processed, non hemocompatible, and non-self macromolecular matrix.

Adult↗

Pseudointima in inflow and outflow conduits of a left ventricular assist system: possible role in clinical outcome.

Activation of blood coagulation and thromboemboli have been shown to present significant clinical risks in patients supported with an left ventricular assist system (LVAS). The interaction of pseudointima (PI) with blood in the conduits of the device could be involved in these clinical complications. Our aim was to study the morphology of the PI versus duration of circulatory support. Novacor N 100 PC LVASs were explanted from 10 men and 2 women after a mean of 209 days (range 23-560 days) of circulatory assistance. PI in the inflow and outflow conduits were investigated with immunohistochemical assays. In the inflow conduits, a loosely adherent PI had built up from collagen type I and III fibers growing into and between fibrin deposits. Disorganized collagenous matrix and longitudinally oriented collagen fibers included alpha-smooth muscle actin positive cells with random orientation. Macrophages were concentrated in the fibrin and were dispersed throughout the extracellular matrix. In the outflow conduits, a thin, adherent PI was composed of regular collagen type I and III layers. Collagen type I fibers had grown into the woven Dacron and alpha-smooth muscle actin positive cells were oriented in the axis of the blood flow. Macrophages were concentrated in the Dacron and reached the inner collagen layers. Venous blood flow in the inflow conduits allows the development of a non endothelialized irregular collagenous matrix intermingled with fibrin and invaded by macrophages. These persistent structural features progress with duration of circulatory assistance and reflect matrix degradation and remodeling. The potential to release thromboembolic fragments from the non stable, thrombogenic PI may be involved in the thromboembolic or neurologic complications sustained by 5 of 12 patients who were on circulatory support for as long as 200 days.

Actins↗

Congenital soft tissue dysplasias: a morphological and biochemical study.

The term congenital soft tissue dysplasias (CSTDs) regroups some localized malformations of covering soft tissues in children, presenting as various clinical entities, either recognized as particular syndromes (e.g., Parkes-Weber, Klippel-Trenaunay, Proteus) or, most often, appearing less stereotyped (e.g., segmental hypertrophy or gigantism, lymphedema, angiodysplasia, phakomatosis), with a common histopathological lesion, the hamartoma. The aim of this paper is to report a morphological and biochemical study of the extracellular matrix of skin and subcutaneous tissue in children with CSTD. For every patient, pathological tissues were compared with contralateral, symmetrical tissues, taken as controls. In all CSTDs, pathological samples were characterized by an increase in water and total glycosaminoglycan (GAG) content with a decrease in collagen content. Other results lead the authors to distinguish two main entities, segmental dysplasia (SeD) and neuroectodermal dysplasia (NeD). Elastic fiber content was increased in SeD and decreased in NeD. Hyaluronic acid (HA) and dermatan sulfate (DS) were increased in NeD, whereas in SeD, HA was decreased with an increase in the DS/HA ratio. Cultured fibroblasts from dysplastic skin had slower proliferation in vitro than fibroblasts from control skin, whereas their biosynthetic activity concerning collagen and GAGs was greater. The difference in the composition of extracellular matrix supports the clinical classification of CSTDs in two main groups: segmental dysplasia with or without gigantism and neuroectodermal dysplasia (in von Recklinghausen's disease and nevi).

Abnormalities, Multiple↗

[Experimental study of a biodegradable micro-arterial prosthesis (author's transl)].

An experimental study of a micro-arterial prosthesis prepared from biological materials was carried out in the rat. The results obtained after two months were analysed in terms of permeability of the biochemical constituants of the vessel and of the neighbouring scar tissue, and endothelial healing. These studies showed the association with a process of proteolysis of the implanted vessel, of a process of reconstruction. They show moreover the quality of the endothelial scar on the internal surface of the vessel.

Animals↗

Vascular substitute from human placental arteries: glycosaminoglycan and elastin synthesis in the neo-intimal hyperplasia.

Heparinized human placental arteries (internal diameter less than or equal to 1 mm) were cross-linked with glutaraldehyde and implanted in infrarenal aortas in rats (n = 78). At three months and one year following aortic replacement, the neo-intimal hyperplasia covering the patent conduits and the host intima media were excised. Glycosaminoglycans (GAGs) and elastin were metabolically labelled in vitro with radioactive glucosamine and valine, respectively. The incorporation of 3H glucosamine into GAGs decreased sixfold in both neo-intima and host intima media from three months to one year. At three months, the 3H label of hyaluronic acid accounted for 66 per cent and 43 per cent of the 3H GAGs in the neo-intima and host aorta, respectively. At one year, 55 per cent of the 3H GAG label were identified as 3H heparan sulphate in the neo-intima and host intima media. From three months to one year, the ratio of chondroitin 4 sulphate (CS 4) to chondroitin 6 sulphate (CS 6) decreased from 6 to 1.5 in the neo-intima, whilst the ratio of CS 4 to CS 6 (0.6) was constant in the host aorta during the experimental period. At one year, the neo-intima contained elastin. The radioactive incorporation pattern of GAGs and the biosynthetic label of valylproline dipeptides indicated a decrease in biosynthetic activity in neo-intimal and the host aortic cells with progressing time in vivo.

Animals↗