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Biomedical subjects

A M Robert

Publications and source records attributed to A M Robert.

18 recordsLinked to original sources
PubMed1979

Biochemical and pharmacological properties of a neurotoxic protein isolated from the blood serum of heavily burned patients.

Blood serum of heavily burned patients contains neurotoxic substances which are not present in normal control sera. In the present paper, we describe the purification by gel filtration and ultracentrifugation of such a neurotoxic factor. The purified factor appeared to be a high molecular weight (2 to 3.10(6) daltons) lipoprotein. This factor was present in all the sera of patients with more than 35 per cent of the body surface burned. When injected into rabbits the lipoprotein caused a flattening of the EEG tracing, then trembling and convulsions with bursts of spikes on the EEG. The activity of this neurotoxic substance was enhanced when the permeability of the blood-brain barrier was increased by previous intraventricular injection of collagenase. The presence of such a neurotoxic factor in the blood serum of burned patients, together with the increased serum collagenase activity they exhibit may explain the neurotoxic symptoms observed in them.

Animals↗
PubMed1979

Biochemical and pharmacological properties of a cardiotoxic factor isolated from the blood serum of burned patients.

Blood serum of severely burned patients contains several substances which are not present in normal sera. One of these substances, a small protein of an approximate molecular weight of 12 to 14,000 daltons displayed a toxic action on the circulatory system. This cardiotoxic factor was obtained in a purified form by alcohol precipitation followed by gel filtration and carboxymethyl cellulose chromatography. The purified preparation seems to be a low molecular weight protein of about 8000 daltons. The biological effects of this substance consist essentially of alterations of the ECG pattern, indicating decreased cardiac output and ischaemia of the cardial muscle. The blood pressure decreases and respiratory function is also altered. The presence of such a toxic factor in sufficient concentration in the blood serum may explain the cardiovascular complications observed in some burned patients.

Animals↗
PubMed1979

Mechanism of action of collagenase on the blood-brain barrier permeability. Increase of endothelial cell pinocytotic activity as shown with horse-radish peroxidase as a tracer.

The ultrastructural mechanism of the protease induced blood-brain barrier permeability-increase was studied with horse-radish peroxidase as a tracer. After intravenous injection of collagenase or pronase, a significantly increased number of pinocytotic vesicles was found in brain capillary endothelial cells. alpha-Chymotrypsine did not exert such an action.

Animals↗
PubMed1979

Influence of anthocyanoside treatment on the cholesterol-induced atherosclerosis in the rabbit.

We have studied the effect of treatment with anthocyanosides from Vaccinium myrtillis on cholesterol-induced atheroma of rabbits. We have found that the drug did not modify the serum cholesterol levels, but decreased the proliferation of the intima the extracellular matrix production the calcium and lipid deposition in the aorta, and the DNA and lipid contents. The alterations in the biochemical composition of the isolated brain microvessels were also diminished. The following mechanism may explain the protective action of the treatment: the collagen of the vessel walls participates in the control of vascular permeability. This permeability is increased by a cholesterol-rich diet. The protective drug interacts with collagen, increasing its cross-links, thus diminishing the permeability in small, as well as in large blood vessels.

Animals↗
PubMed1978

Serum elastase and its inhibitors in the blood of heavily burnt patients.

Serum elastase and its inhibitors were determined in the sera of heavily burnt patients. Serum elastase levels were elevated at two to eight days after a severe burn-accident and returned towards normal values from the 10th day on. Both alpha1-antitrypsin and alpha2-macroglobulin levels were also elevated in the sera of heavily burnt patients. alpha1-Antitrypsin showed a parallel evolution to the elastase level but alpha2-macroglobulin followed a somewhat different time curve. Plasminogen and antithrombin were not elevated significantly. It is suggested that serum elastase may play a role in tissue degradation in burnt patients.

Antithrombin III↗
PubMed1978

Serum proteins in heavily burnt patients.

Several serum proteins, such as prealbumin, protease inhibitors, immunoglobulins, metalloproteins and inflammatory glycoproteins were determined in the sera of heavily burnt patients by radial immunodiffusion. An increase of acute phase reactant glycoproteins (orsomucoid, haptoglobin, haemopexin, C-reactive protein), C3-complement, immunoglobulins, prealbumin and of the protease inhibitors (a1-antitrypsin, a2-macroglobulin) was found. For some proteins, such as prealbumin, haemopexin, immunoglobulins, this increase was preceeded by a decrease on days 3 to 5 post-burn. The time course of the increase was variable, faster for some patients and slower for others: orosomucoid, C-reactive protein, C3-complement reached peak values between days 6 and 8; immunoglobulins and hemopexin decreased then towards normal values. No significant increase was found for ceruloplasmin, transferrin, beta2-glycoprotein, a2-SH glycoprotein and GC-globulin. It is proposed that the selective overproduction of the above mentioned proteins may be related to the stimulation of acute-phase reactant protein synthesis by the liver as a result of tissue breakdown produced by the circulating proteases and especially by elastases and collagenases as was shown previously (Miskulin et al., 1978; Moati et al., 1978a).

Blood Proteins↗
PubMed1977

Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood brain barrier.

Proteases and especially collagenase injected into the lateral brain ventricles of rats are able to increase the permeability of the blood-brain barrier to trypan blue. Treatment of the rats with anthocyanosides of Vaccinium myrtillis diminishes the permeability increasing effect of collagenase and accelerate the recovery of normal permeability. This effect seems to be related to a less effective enzymatic attack on collagen, as hydroxyproline content in the CSF is increased less after collagenase injection in treated animals than in untreated controls.

Animals↗
PubMed1977

[Demonstration and partial characterization of cardiotoxic and neutrotoxic substances in the serum of burnt patients (author's transl)].

Cardio-circulatory and neurological complications may appear between the second and seventh day of treatment of severely burnt (greater than 30% of body surface, 3rd degree) patients between the 2nd and 7th day, even if their lesions follow an apparently favorable course. The purpose of the present work was to isolate substances from the sera of such patients which would be responsible for the toxic effects. The sera of several patients were fractionated by Cohn's method n degree 6 and the fractions were tested in vivo in rabbits, rats and mice for their toxic effects. We could demonstrate in some of the fractions (II + III, IV and VI) toxic activity on the central nervous system, on the cardiocirculatory and respiratory systems. An acute toxic activity was also present as well as a substance increasing the permeability of the blood-brain barrier. All these factors together may be involved in the production of the above-mentioned clinical symptoms. Their appearance may depend on the concentration of toxic substances in the blood and on the resistance of the patients.

Animals↗
PubMed1977

Comparative study on the composition of the organic matrix of the long bones of the "normal" rat and of the mutant Op/Orl.

The organic matrix of the long bones of the "normal" rat strain and of its mutant Op/Orl were investigated. This latter strain exhibits some anomalles similar to Albers-Schönberg disease as well as tooth retentions. Bones (tibia, femur) were incubated with 14C-glucose and also submitted to a fractional extraction procedure (EDTA, urea) to separate soluble and insoluble fractions. The proteins, hexoses, hexosamines, hydroxyproline content of these fractions was determined as well as the radioactivity of the soluble extracts Glycosaminoglycans were also studied by cellogel electrophoresis after pronase digestion of the EDTA-extracts. Male and female animals of each strain were studied separately. The relative amount of soluble proteins (EDTA + urea extracts) was the same in both strains, the mineral content of the final residue was however higher in the mutant Op/Orl strain. The hydroxyproline content of the mutant-extracts were lower than in the original strain suggesting a lower soluble collagen content. This may be due to a faster polymerisation, insolubillisation of freshly synthesised collagen. The hexosamine content of the mutant urea extracts and the final residue was higher than that found in the analogous extracts obtained from the normal "normal" strain, suggesting a higher proportion of structural glycoproteins in the mutant bone, uronic acid being low or absent. Some other parameters were identical between the mutant and original strains but differed between males and females. The radioactivity of the soluble extracts was higher in the males than in females. The glycosaminoglycans of the EDTA extracts are also different: male-extracts show two bands on cellogel electrophoresis, one corresponding to chondroitin-sulphate, the other to hyaluronate. Females showed only the chondroitin sulphate band. The aminoacid composition of the insoluble residue of males was higher in basic amino acids (lysine, histidine, arginine) than the female extracts. These results indicate the existence of discrete well defined differences between the organic matrix of the orginal and mutant strain on one side and between male and female bones on the other side.

Amino Acids↗
PubMed1977

Matrix biology and pathology, a new branch of biomedical sciences.

The macromolecules of the intercellular matrix (MM) : collagen, elastin, proteoglycans and structural glycoproteins) are present in all tissues in variable amount and proportion. Some tissues, particularly rich in MM are designated as "connective tissues". Matrix macromolecules assure the integration of cells in tissues and of tissues in organs and in the whole organism. Differentiation, morphogenesis, maturation and aging are characterized by the variation of the raltiave rates of synthesis of individual MM-s. Several post-transcriptional and post-translational steps play an important role in biosynthesis of MM-S offering a multitude of possibilities for genetic and/or aquired anomalies. Recent progress in the descriptive and dynamic biochemistry of MM-s sheds new light on these anomalies which condition a whole class of diseases (the diseases of the intercellular matrix or matrix pathology). The molecular and cellular mechanisms of several of these diseases start to be understood. As the great majority of the important disease of occidental societies (such as vascular and articular diseases, diabetes, and the pathology of aging) belong to this category, intensive research in matrix biology and pathology as well as of its teaching in the medical curriculum should be considered as first priorities.

Chemical Phenomena↗
PubMed1976

Biochemical studies on dacron arterial prostheses.

Dacron arterial prostheses, treated or not with biopolymers (gelatin, glycosaminoglycans) were implanted in the abdominal aorta of dogs and the connective tissue synthetised inside and outside the prosthesis was studied. After 3 and 9 months of implantation the prosthesis, a joining portion and a piece of aorta were excised and put in organ culture with 14C-lysine for 3 days. Representative macromolecular extracts were then obtained by a "chemical dissection" procedure. The radioactivity and the chemical composition of these extracts was studied. The DNA content of the prosthesis was higher than that of the adjacent aorta showing a dense cellular repopulation of the prosthesis. This was confirmed by histology also which revealed the presence of a newly formed limiting elastic membrane and the presence of numerous elastic fibrils. Collagen, elastin and glycosaminoglycans could be detected in the macromolecular extracts showing that the cells which repopulated the prosthesis expressed a complete biosynthetic capacity as far as matrix macromolecules are concerned. The distribution of proteins in the extracts was as follows: 4% of total proteins were extracted in a 1M CaCl2-buffer 80% of total proteins in the collagenase extracts, 10% in the 6M urea extract. Only 0,2% of proteins were in the final elastase extract, 10 times less than in the joining aorta fragment. The proportion of the other proteins was similar in aorta and in the prosthesis as well as the chemical composition (hexosamine and hydroxyproline content) of the extracts. The proportion of collagenase-extractable proteins decreased with the time of implantation (from 3 to 9 months) and the proportion of urea-extractable proteins increased. This type of modification is similar to that found in aging aorta wall. 14C-lysine was actively incorporated in all macromolecular fractions studied. The incorporation pattern of the prothesis tissue was similar to that found for the joining host aorta, showing a similar regulatory tendency for matrix macromolecules. It appears therefore that a valid hemocompatible vascular type of connective tissue can be synthesised on the dacron arterial prosthesis and nature of this connective tissue can be influenced by previous biopolymer treatment of the synthetic prosthesis. The described procedure (incorporation of labelled precursors in organ culture) appears to be a valid method for the exploration of the regulatory processes underlying the synthetic capacity for matrix macromolecules of the newly formed tissue in the synthetic prosthesis.

Animals↗
PubMedDate not supplied

[Biochemical modifications of connective tissue induced by the non-saponifiables of avocado and soya-bean oils administered percutaneously in the "Hairless" rat (author's transl)].

A mixture of non-saponifiable fractions of avocado and soya-bean oils was administered percutaneously, for fifteen days, in a 5% dilution in decanol. They resulted in modifications of constituents of connective tissue of the treated skin and in subjacent carrageenan induced granulome. The effect on the granuloma was reduced to an increased total protein content. As for the skin, the effect of the non-saponifiables was different from that induced by the vehicle by an increase of water and lipids and an increased level of soluble proteins, including collagen, as compared to insoluble proteins. The results are in agreement with those obtained using the non-saponifiables taken orally but the effects appear sooner and are localized essentially at skin level.

Animals↗