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Biomedical subjects

J Labat-Robert

Publications and source records attributed to J Labat-Robert.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Fibronectin, aging and related pathologies].

It could be demonstrated that plasma and tissue fibronectin (FN) increase with age. Some age dependent diseases as diabetes, osteoarthritis and Werner syndrome produce also an increase of tissue fibronectin biosynthesis. Plasma fibronectin decreases in diabetes and in breast cancer. Alternative splicing of the FN gene appears also to vary with age and in some related pathologies. Nutritional status and UV light also influence FN biosynthesis. It appears therefore that the determination of plasma FN and its isoforms as well as the study of tissue FN may be of interest for the study of chronological aging and related pathologies.

Age Factors↗
PubMed1990

Extracellular matrix.

A succinct overview of recent results on the biochemistry of extracellular matrix (ECM) is presented. The rapid expansion of this discipline over the best decades renders impossible to give an even approximately complete coverage of matrix biology. Some selected results concerning the four major families of macromolecules composing the ECM, that is, collagens (14 types described), elastin(s), proteoglycans and structural glycoproteins (especially fibronectin) are described. Special attention is directed to a crucial aspect of matrix biology: cell-matrix interactions. A number of cell membrane receptors were recently described mediating the two way information flow from the cells to the matrix via the 'programme' of ECM synthesis coded in the genome and unfolding during differentiation and from the ECM to the cells through the membrane receptors which contact the cytoskeleton. One of them at least, the elastin receptor was shown to be linked through a G-protein-phospholipase C-IP3 mediated relay to the regulation of intracellular calcium. Modifications of the ECM will therefore influence cell behaviour. Derangements of this informational feed back mechanisms appear to be involved in most age-related connective tissue diseases.

Animals↗
PubMed1990

Interaction between fibronectin, proteoglycans and lipoproteins.

The effect of purified human plasma fibronectin on LDL-GAG and LDL-PG complex formation was studied. Fibronectin added to LDL or to GAG or even to preformed LDL-GAG-Ca2+ complexes could inhibit complex formation and dissociated preformed complexes. Similar results were obtained with total serum instead of purified LDL: 1.2 mg fibronectin added to 1.0 mg LDL-cholesterol completely inhibited insoluble complex formation in the presence of Ca2+ between LDL and GAGs or LDL and PGs purified from aorta, whatever the order of mixing of the macromolecules. When fibronectin was added to preformed PG-LDL complexes however dissociation was less complete than with preformed LDL-GAG complexes (60% dissociation instead of 100% at similar concentration ratios). It appears therefore that the protein and GAG portions of PGs may not interact at the same sites of LDL and competition by fibronectin would be more efficient at the GAG binding site. Fibronectin could also dissociate LDL-heparin complexes formed on heparin-Sepharose affinity columns. As PG-LDL complexes were isolated from atherosclerotic plaques and fibronectin was also shown to increase in plaque area and exhibit opsonic-like functions, the above findings may well have physiopathological significance.

Binding Sites↗
PubMed1989

Biosyntheses of interstitial collagens and fibronectin by porcine aorta smooth muscle cells. Modulation by low-molecular-weight heparin fragments.

The effect of low-molecular-weight heparin fragments (CY222) on the biosynthetic phenotype of porcine aortic smooth muscle cells (SMC) was investigated in vitro on overconfluent cell cultures. Addition of increasing concentrations of CY222 to the culture medium of early passage SMC resulted in a dose-dependent decrease of type III to type I collagen ratio without change in total collagen biosynthesis. In the same range of concentrations CY222 did not affect the biosynthesis of fibronectin. However, heparin fragments decreased the proportion of the freshly synthesized pericellular form of fibronectin with a concomitant increase of neosynthesized intracellular fibronectin, indicating an inhibitory effect of CY222 on fibronectin secretion. Our results demonstrate that the biosynthetic phenotype of SMC in vitro can be modulated by low-molecular-weight heparin fragments and confirm also that interactions between cells and extracellular matrix molecules can modify the biosynthetic pattern of mesenchymal cells.

Animals↗
PubMed1989

Heparin fragments regulate collagen phenotype and fibronectin synthesis in the skin of genetically diabetic mice.

The biosyntheses of interstitial collagens of type I and III and of fibronectin were studied in genetically diabetic KK mice, as compared to control C57 Black mice, as well as the effect of low-Mr heparin fragments (CY 222) on these biosyntheses. An increased production of type III collagen, as compared to type I collagen, could be demonstrated in explant cultures of KK mice skins. Fibronectin biosynthesis was also increased. In vivo treatment of KK mice with 1 mg/kg of CY 222 decreased the biosyntheses of type III collagen and of fibronectin to normal levels. These experiments suggest that low-Mr heparin fragments can modulate the expression of extracellular matrix macromolecules.

Animals↗
PubMed1988

Aging of the extracellular matrix and its pathology.

Recent concepts on the mechanisms of aging of extracellular matrix (EM) are reviewed as well as its involvement in age-associated diseases. Cell differentiation, histogenesis and organogenesis can be analyzed in terms of the program of the biosynthesis of EM macromolecules during development, maturation and aging. The most important biological role of EM is the integration of cells in tissues, of tissues in organs and of organs in the whole organism. EM can directly influence cell behavior through the contact between EM and the genome mediated by structural glycoproteins (fibronectin, laminin, elastonectin, etc.) interacting with other EM macromolecules (collagen, proteoglycans, elastin) and the cytoskeleton by trans-membrane receptors (integrins). Most age-associated diseases exhibit a deviation (qualitative or quantitative) from the normal program of EM biosynthesis. Three examples are analyzed in some detail: atherosclerosis, diabetes and malignant tumors. The degradation of elastic fibers catalyzed by cellular elastase-type enzymes is observed in atherosclerosis and also in emphysema and skin aging. Several of these enzymes were isolated and characterized from platelets, fibroblasts, smooth muscle cells and lipoproteins. The biosynthesis of some of them increases with age and facilitates cell migration. Plasma fibronectin increases with age exponentially. This increase is absent or strongly attenuated in diabetes and some cancers. Tissue fibronectin increases in diabetes, Werner syndrome and in the peritumoral desmoplastic reaction while most tumor cells can no more retain fibronectin on their membrane facilitating their movement in the organism. These examples demonstrate the importance of the study of cell matrix interactions for gerontology.

Aging↗
PubMed1988

[Study of an optimal biological profile for demonstrating pancreatic involvement in acute abdominal syndrome].

The authors have studied several seric, plasmatic and urinary constituents in patients hospitalized for an acute abdominal syndrome to be able to characterize an eventual pancreatic lesion; mainly seric and urinary amylase as well as its isoenzymes, lipase, liver profile and trypsin. In acute pancreatitis, the means of the maximal increases of seric amylase, lipase and trypsin are respectively: 10.7; 21.6 and 19.2 X N (upper normal limit) whereas in chronic pancreatitis, these elevations are 6.5 X N for amylase and 9.5 XN for lipase. The authors observed at J1 (first day of hospitalisation) and at J2 an increase in seric amylase, lipase and/or liver profile respectively in 95, 90 and 25 p. cent of acute pancreatitis; in 86, 86 and 14 p. cent of chronic pancreatitis and 43, 39 and 86 p. cent of bili duct diseases. In conclusion, it appears compulsory to run a liver profile with the pancreatic enzymes (amylase and lipase) to diagnose a pancreatitis in presence of an acute abdominal syndrome.

Abdomen, Acute↗
PubMed1988

Plasma fibronectin in mammary and uterine carcinomas.

Plasma fibronectin was determined in cancer patients and in age- and sex-matched controls and analyzed as a function of age, size of tumor, receptor content of the tumor, metastases and treatment. In the control population, plasma fibronectin increased with age exponentially. The age-dependent increase in plasma fibronectin was strongly attenuated in the cancer population. As normal and cancer curves intersect at about 40-46 years, below this age cancer plasmas have slightly higher values than normal, above this age the inverse is true. No correlation was found between estrogen or progesterone receptor levels and plasma fibronectin values, nor with plasma albumin. Tumor patients with distant metastases gave slightly but significantly higher values than those with local or no metastases. No significant difference was found between tumors when Bloom grading was taken as the second parameter instead of age. The size of the tumor or the type of treatment had no influence. Increased proteolytic activity, increased trapping of plasma fibronectin in tissues and especially in the stromal (desmoplastic) reaction and/or modifications in plasma fibronectin biosynthesis may well be responsible for these results.

Adenocarcinoma↗
PubMed1987

Increased biosynthesis and processing of fibronectin in fibroblasts from diabetic mice.

Diabetic connective tissues exhibit a deranged regulation of extracellular matrix biosynthesis. Fibronectin is shown to be increased in human dermal connective tissue by immunofluorescence, mainly at the dermoepidermal and capillary basement membranes. The rate of fibronectin biosynthesis, excretion, and incorporation in a pericellular polymeric form was investigated using genetically diabetic KK mouse skin and fibroblasts as compared to Swiss and C57BL mouse skin and fibroblasts. The rate of incorporation of [35S]methionine into proteins recovered in the culture medium or in deoxycholate and NaDodSO4 or urea extracts was investigated. The rate of incorporation in the medium and deoxycholate extracts was comparable. However, the relative rate of incorporation of the tracer in the NaDodSO4-extractable, pericellular polymeric form was increased in the diabetic KK fibroblasts both for total proteins and for fibronectin. In pulse-chase experiments, the deoxycholate-soluble and NaDodSO4-soluble fractions exhibited a precursor-product relationship. The rate of passage of fibronectin from the deoxycholate-soluble (cellular compartment) form to the NaDodSO4-soluble (pericellular polymeric) form was strongly accelerated in the diabetic fibroblast cultures. These results confirm the increased rate of synthesis of fibronectin in diabetic fibroblasts as well as its processing from the cellular compartment to the polymeric pericellular form. The increase of fibronectin in diabetic connective tissues, in the matrix as well as in the basement membranes, may play a role in the mechanism of micro- and macroangiopathies and in the perturbed permeability characteristics of the diabetic capillaries, and as a glycoprotein it may contribute to the increased periodic acid/Schiff reagent staining of diabetic capillary basement membranes.

Animals↗
PubMed1987

Parallel increase of plasma fibronectin and perchlorosoluble serum glycoproteins in radiation-induced lung damage.

A study of the behavior of plasma fibronectin during a radiation-induced inflammatory lung reaction was carried out. Rats were exposed to a single homogenous thoracic irradiation of 15 Gy from a 60Co gamma source. Perchlorosoluble glycoproteins were determined (as sialic acid) as well as plasma fibronectin at 2, 8, 27, 60 and 120 days after irradiation. A parallel increase of the perchlorosoluble glycoproteins and plasma fibronectin was found. Morphological and histological studies of the irradiated lungs showed a predominating endothelial cell injury in the lung microcapillaries. The parallel increase of plasma fibronectin and perchlorosoluble serum glycoproteins suggests that plasma fibronectin can be considered as an acute phase reactant. Its early increase may be the result of the inflammatory reaction and endothelial injury induced by the radiation.

Animals↗
PubMed1986

[Macromolecules of the extracellular matrix].

In this introductory paper, the authors review the macromolecular basis of extracellular matrix. 4 principal groups of macromolecules are known: collagen, elastin, proteoglycans and structural glycoproteins. The phylogenetic evolution lead to the great complexity of this matrix. The interest of a more specific pharmacology directed towards this extracellular matrix is emphasised.

Chemical Phenomena↗
PubMed1985

Biosynthesis of laminin and fibronectin by rat satellite cells during myogenesis in vitro.

The biosynthesis of fibronectin and laminin was studied in satellite cells cultured from adult rat muscles before (day 4) and after fusion and formation of myotubes (day 14) using (35S) methionine as a tracer. The kinetics of incorporation into immunoprecipitable fibronectin and laminin were recorded at intervals from 1.5 to 24 hours of incubation with the tracer from the cells, the pericellular matrix and the culture medium. The rate of synthesis of fibronectin and laminin expressed as dpm/microgram DNA were constant from the mononucleated cell to the myotube state. Both glycoproteins were detected in the cells and in the pericellular matrix. When the results were expressed as the percentage of incorporation into total protein, major changes could be observed in the early phase of the kinetic studies in the cells and the pericellular matrix. Both showed an increase from the mononucleated myoblast to myotube, suggesting that an increasing fraction of total protein biosynthesis is directed towards these two extracellular matrix glycoproteins. At the same time, there was a decrease in the secretion into the medium of freshly synthesized radiolabeled fibronectin and laminin. Our results confirm the synthesis of varying ratios of both extracellular matrix macromolecules by undifferentiated mononucleated myogenic cells as well as myotubes.

Animals↗
PubMed1985

Fibronectin, laminin, type I, III and IV collagens in Duchenne's muscular dystrophy, congenital muscular dystrophies and congenital myopathies: an immunocytochemical study.

The distribution pattern of fibronectin, laminin, type I, III and IV collagens in human skeletal muscle was studied by immunofluorescence. In normal muscle, as well as in congenital myopathies (CM), type I and III collagens were localized in the endomysium and the perimysium. Laminin and type IV collagen delineated precisely each muscle fiber but did not stain the perimysium. In Duchenne's muscular dystrophy (DMD) as well as in congenital muscular dystrophies (CMD) the extensive proliferation of connective tissue consisted mainly of fibronectin and type I and III collagens. Laminin and type IV collagen delineated principally the basal lamina but suprisingly were found to be distributed to some extent all over the extracellular matrix. No disease--specific accumulation of components of the extracellular matrix was found which would enable us to differentiate these last two diseases, though the immunofluorescence reactions for all components were stronger in DMD than in CMD.

Adolescent↗
PubMed1985

Comparative distribution patterns of type I and III collagens and fibronectin in human arteriosclerotic aorta.

The distribution patterns of type I and III collagens and fibronectin were studied in arteriosclerotic lesions of human aortas as well as in the regions devoid of any macroscopic lesions of the same aortas. Frozen sections were analyzed for fibronectin and collagens by indirect immunofluorescence or immunoperoxidase analysis with specific antisera prepared in rabbits against human plasma fibronectin and against human type I and III collagens. Tissue samples were also stained for type I and III collagen distribution using Picro Sirius red according to the method described by Junqueira et al. (1979). In the regions devoid of any visible macroscopic lesions, there is a co-distribution in the media of the aortic wall of type I and III collagens, with a predominance of type I collagen. Type I collagen is also visible in the intima, as a continuous layer. This is attributed to an age-dependent change of the aorta (arteriosclerosis). Fibronectin can be demonstrated as a thin layer in the subendothelium and as a weak immunofluorescence over the media. In recent or evolutive arteriosclerotic plaques, fibronectin and type III collagen appear to be strongly increased and superimposed. There is also an increase of type I collagen in the intimal region of the plaque. The co-distribution of type III collagen and fibronectin in the arteriosclerotic plaques may suggest a tissue-repair-type of process, analogous to that which can be observed during wound healing. Our results suggest that in arteriosclerotic lesions, type III collagen and fibronectin are predominantly synthesized.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗