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Biomedical subjects

L Cohen-Solal

Publications and source records attributed to L Cohen-Solal.

At least 37 records · Page 2Linked to original sources
PubMed1986

Abnormal procollagen synthesis in fibroblasts from three patients of the same family with a severe form of osteogenesis imperfecta (type III).

Dermal fibroblast cultures from three siblings with a severe form of osteogenesis imperfecta were established in order to analyze their procollagen and collagen synthesis. Cell strains from clinically normal consanguineous parents (first cousins), were also obtained for comparison. Total collagen production in culture media was diminished by 55% in the patients fibroblasts and to a lesser extent in the parents. This decrease was specific for collagenous proteins. From polyacrylamide gel electrophoresis, it appeared that the three children had not only the same defective secretion of pro alpha 1(I) molecules but that their pro alpha 1(I) migrated slightly faster than the parental and control counterparts. Analysis of secretion confirmed a reduced rate in procollagen synthesis and the absence of intracellular storage. Upon pepsin treatment, extracellular alpha 1(I) and alpha 2(I) chains were found in the expected ratio of 2:1 and migrated normally, suggesting that the altered mobility of pro alpha 1(I) chains was related to COOH or NH2 terminal propeptides. In agreement with the reduced type I collagen production, an increase in the alpha 1(III)/alpha 1(I) ratio was also detected. Furthermore, after a 2.5-h labelling followed by alkylation with iodoacetamide, free intracellular pro alpha 2(I) and alpha 1(I) chains were detected in the absence of reduction, consistent with an abnormal intracellular ratio of pro alpha 1(I)/pro alpha 2(I) that was measured after dithiothreitol reduction. Analysis of intracellular collagen chains from parental strains following a 4-h incubation demonstrated that pro alpha 1(I) appeared as a doublet, one band with normal mobility and a less intense band migrating faster and corresponding to the defective chain found in the patients. Absence of the abnormal molecules in culture media was related to the demonstration of a defective collagen secretion by parental fibroblasts. Correlation between these biochemical findings and clinical data strongly support a recessive inheritance of the disease that could be classified as a type III form of osteogenesis imperfecta. Patients would be homozygous for the same defective allele and the asymptomatic parents would most likely be heterozygous carriers of the mutation. Although the exact location of the alteration is not yet elucidated, a splicing mutation is suggested.

Adolescent↗
PubMed1986

The differential symptomatology of errors of collagen metabolism: a tentative classification.

We address the confusion in the current classification of inherited disorders of collagen and the excessive extension of the concept of the Ehlers-Danlos "syndrome" that tends to cover many facts and conditions frequently without strong clinical connection. We propose to subdivide the collagen disorders into four main classes depending on whether skin, joints, bone, or blood vessels are mainly involved. The class with mainly skin involvement includes the different forms of cutis laxa, Ehlers-Danlos syndrome types I and II (autosomal dominant), types V and IX (X-linked recessive), type VI (autosomal recessive), and type VIII (autosomal dominant). The group with mainly articular involvement includes Larsen and related syndromes and other types with a more benign course. The conditions with mainly skeletal involvement include the different forms of osteogenesis imperfecta. The class with mainly blood vessel involvement includes disorders of type III collagen and the Marfan syndrome. This tentative classification proposes a logical clinical framework that will allow easier integration of molecular biology data.

Bone Diseases↗
PubMed1986

Proline hydroxylation of collagens synthesized at different temperatures in vivo by two poikilothermic species.

Extent of prolyl hydroxylation in newly synthesized viper collagen is decreased at 10 degrees C to approximately 23% of normal on skin and to approximately 57% of normal in bone collagen. At 20 degrees C, prolyl hydroxylation is approximately 50% of normal in skin and normal in bone. At 10 degrees C and 20 degrees C, prolyl hydroxylation is decreased approximately 32% in the skin collagen of carp. In contrast, prolyl hydroxylation is unchanged at 10 and 20 degrees C in bone, scale and lepidotrichia. Prolyl hydroxylation of cartilaginous endoskeleton showed an approximately 25% decrease at 20 degrees C.

Acclimatization↗
PubMed1986

[Antenatal forms of osteogenesis imperfecta. Classification trial].

A classification of the different types of osteogenesis imperfecta is proposed. There are 3 main groups: the lethal type, the severe type and the so-called regressive type, with a more favorable course. This classification was established to allow for a more precise definition of the prognosis at the time of birth, or even in utero when diagnosis is made by ultrasonography. It should also allow for better classification of the data obtained by the study of the molecular collagen. This project is different from Sillence's one by the exclusion of type II B lethal types, which are often compatible with survival. In view of the frequent occurrence of a dominant mutation in the type II A, the more generally accepted recessive transmission is discussed.

Diagnosis, Differential↗
PubMed1985

Reaction products formed after strong acid treatment of alpha-amino-delta-hydroxyvaleric acid.

High-voltage paper electrophoresis and analytical and preparative amino acid ion-exchange chromatography were used to investigate the products resulting from strong acid treatment and strong acid treatment and subsequent alkalinization of alpha-amino-delta-hydroxyvaleric acid. After strong acid treatment, alpha-amino-delta-hydroxyvaleric acid and proline, as well as several unidentified components, presumably lactones, were recovered. No definitive identification of the putative unstable lactones was accomplished either by physical-chemical means or by ion-exchange chromatography or high-voltage paper electrophoresis. Nevertheless, after acid treatment and alkalinization, only alpha-amino-delta-hydroxyvaleric acid and proline were recovered, in approximately equal amounts. The formation of such large amounts of proline from the acid treatment and alkalinization of alpha-amino-delta-hydroxyvaleric acid is therefore an important consideration in quantitating the number of gamma-glutamyl phosphate residues present in various proteins.

Acids↗
PubMed1985

Age related evolution of stable collagen reticulation in human skin.

The relaxation time of hydrothermal isometric tensions (HIT) was measured in different tissues during collagen hydrolysis. This hydrolysis was shown to have the same activation energy in all skin samples studied, whatever the species and age. Therefore, variations in the HIT relaxation half-time at the boiling point, exclusively reflected variations in the reticulation degree of the stable infinite network of denatured collagen. Stable collagen reticulation was studied in human skin from birth to 70 yrs of age in 113 biopsies, by measuring the relaxation half-time of hydrothermal isometric tension (HIT) at boiling point. This time was observed to vary in three different ways as a function of age: 1) from birth to eight or 10 yrs and from 14-15 yrs until adulthood, it increased constantly, and at the same rate; 2) during early puberty, the striking observation was the dramatic decrease of relaxation time value which remained low for 4-5 yrs thereafter, and 3) from adulthood to 70 yrs of age, relaxation time values were scattered along several plateaux, apparently separated by similar incremental steps. A parallel study on rat and pig skin showed a similar age-related evolution for collagen stable reticulation i.e., a sudden drop of reticulation at puberty, and low values for several months thereafter, followed by a linear increase, at the same rate as that observed for human skin. The study of collagen reticulation in various pathological situations may help to clarify and increase our understanding of the different mechanisms involved in collagen modifications during in vivo growth and aging.

Adolescent↗
PubMed1985

Tendon adaptation to different long term stresses and collagen reticulation in soleus muscle.

Leg immobilization with or without soleus muscle denervation was studied in young rabbits. Muscle and tendon were maintained in extension, i.e., in the most lengthened position. Length measurements performed on sarcomeres, muscle fibers and tendon-plus-muscle complexes suggest the following progression in tendon growth rates: normal less than denervated-extended less than innervated-extended. Collagen reticulation was studied as a function of fiber location along these tendons by measuring hydrothermal isometric tension (HIT). Large variations were observed depending on fiber location, and significant modifications were induced by immobilization in extension. The results are discussed in relation to stress as a possible factor controlling collagen maturation in connective tissues.

Adaptation, Physiological↗
PubMed1984

[Lethal osteogenesis imperfecta. Definition and heterogeneity].

The lethal form of osteogenesis imperfecta must be more clearly defined than it is. Early death of the child is not a sufficient criteria since it is observed in other forms compatible with survival. The authors therefore insist on the innumerable fractures of the ribs giving the particular aspect described as "bamboo ribs". These are observed in practically all cases. Heterogeneity however is undoubtful and an X-ray film is reproduced showing thin ribs without fractures in another exceptional lethal form. Genetic and very recent biochemical investigations suggest a new heterogeneity of the lethal form, even well defined clinically and radiologically. Contrary to earlier and frequent statements, it results most often from a dominant mutation, while recessive inheritance is much rarer, therefore the overall risk of recurrence much below 25%.

Female↗
PubMed1983

Hydrothermal isometric tension curves from different connective tissues. Role of collagen genetic types and noncollagenous components.

Variations in hydrothermal isometric tension (HIT) were recorded in tendons, ligaments, skin, blood vessels, nerves, palatal mucosa, lungs, muscles, cartilages, demineralized bones and dentine from donors of different ages and species. The curves obtained during a linear rise in temperature from 37 degrees C to 100 degrees C at a rate of 1.15 degrees C/min were classified into three major families, A, B and C, depending on whether these curves displayed an early maximum, two shoulders or a late maximum. The ratio of heat-labile to heat-stable cross-links in the tissue's collagen network was shown to determine the type of curve obtained, but the genetic types of collagen in the tissue and the amount and quality of its noncollagenous components were not important in this respect. These results are discussed in the light of the accepted view that HIT variations are due to the rubber-elastic properties of gelatin.

Animals↗
PubMed1982

Changes in phosphoproteins of chicken bone matrix in vitamin D-deficient rickets.

Vitamin D-deficiency and rickets was produced in growing chicks. The resulting decrease in mineralization of whole bone and of fractions separated by density centrifugation was accompanied by a very significant decrease in the contents of O-phosphoserine and O-phosphothreonine. Likewise, the total amount of O-phosphoserine and O-phosphothreonine and the concentrations of these phosphoamino acids in EDTA extracts and in fractions obtained by molecular sieving was also reduced. These data provide the first in vivo evidence that phosphoproteins may be critically involved in the calcification of bone.

Animals↗
PubMed1982

Alterations of the gamma-carboxyglutamic acid and osteocalcin concentrations in vitamin D-deficient chick bone.

The content of osteocalcin and protein bound gamma-carboxyglutamic acid (Gla) was studied as a function of bone maturation and mineralization in normal and vitamin D-deficient, rachitic chickens. The Gla/Ca2+ ratio was elevated in rachitic bone, particularly in the most undermineralized regions. For example, there is a 10- to 20-fold elevation in Gla/Ca2+ in the newly synthesized, least mineralized rachitic bone fraction, which progressively decreases to a 1.5-fold elevation in the most highly mineralized areas of rachitic tissue. Osteocalcin, which is the principal Gla-containing protein of mature bone, was quantitated by radioimmunoassay using specific antiserum to the 5670-dalton chicken protein. Surprisingly, the osteocalcin concentration is decreased 50% in vitamin D-deficient bone. From this we infer that accumulated Gla-containing protein in vitamin D-deficient and poorly mineralized bone may possibly represent a precursor of osteocalcin.

1-Carboxyglutamic Acid↗
PubMed1982

The rate of collagen maturation in rat and human skin.

Hydrothermal Isometric Tension (HIT) relaxation was observed at the boiling point in rat, cat and human skin samples of different ages, after raising the temperature from 37 degrees to 100 degrees C at a rate of 1.15 degrees C/min. A Maxwellian relaxation to nearly zero was observed at the boiling point. A given velocity constant characterized a given tissue whether experiments were performed under pressure or under tensile stress. However, the velocity constant of the relaxation decreased as a function of age for all three species during the period studied. Moreover, the velocity constant decreased at the same constant rate for skin samples of cats aged 1 to nearly 5 years, of rats aged from 9 to 28 months and of children from birth to 10 years. We propose a model, based on the well known rubber-elastic properties of the denatured collagen network. In this model (1) HIT decreases as an exponential function of time during bond scission along the polymeric chains; (2) the velocity constant of the relaxation process is proportional to the rate of bond rupture and inversely proportional to the number of stable polymeric chains originally present per unit volume; (3) the evolution of the velocity constant as a function of aging finds an explanation. The HIT test should find useful applications in pathology and pharmacology, since it provides rapid, precise information on the stable state of collagen reticulation in small biopsies.

Age Factors↗
PubMed1979

Identification of organic phosphorus covalently bound to collagen and non-collagenous proteins of chicken-bone matrix. The presence of O-phosphoserine and O-phosphothreonine in non-collagenous proteins, and their absence from phosporylated collagen.

Non-collagenous phosphoproteins, almost all of which can be extracted in EDTA at neutral pH in the presence of proteinase inhibitors, are identified in the matrix of chicken bone, and are therefore not covalently bound to collagen. Similarly, all the peptides containing gamma-carboxyglutamic acid are present in the EDTA extract and none in the insoluble residue, confirming that none is covalently linked to chicken bone collagen. However, organic phosphorus is also found to be present in chicken bone collagen, principally in the alpha2-chains. Of the total protein-bound organic phosphorus present in chicken bone matrix, approx. 80% is associated with the non-collagenous proteins and 20% with collagen. The soluble non-collagenous proteins contain both O-phosphoserine and O-phosphothreonine and these account for essentially of their organic phosphorus content. In contrast, collagen contains neither O-phosphoserine nor O-phosphothreonine. Indeed, no phosphorylated hydroxy amino acid, phosphoamidated amino acid or phosphorylated sugar could be identified in purified components of collagen, which contain approximately four to five atoms of organic phosphorus per molecule of collagen. Peptides containing organic phosphorus were isolated from partial acid hydrolysates and enzymic digests of purified collagen components, which contain an as-yet-unidentified cationic amino acid. These data, the very high concentrations of glutamic acid in the phosphorylated peptides, and the pH-stability of the organic phosphorus moiety in intact collagen chains strongly suggest that at least part of the organic phosphorus in collagen is present as phosphorylated glutamic acid. This would indicate that the two major chemically different protein fractions in chicken bone matrix that contain organic phosphorus may represent two distinct metabolic pools of organic phosphorus under separate biological control.

1-Carboxyglutamic Acid↗
PubMed1979

Identification of gamma-glutamyl phosphate in the alpha 2 chains of chicken bone collagen.

Purified components of chicken bone collagen contain approximately 4 atoms of organic phosphorus per mol of collagen, located principally in the alpha 2 chains. Previous analyses have demonstrated the absence of O-phosphoserine, O-phosphothreonine, and other phosphorylated hydroxy amino acids, phosphoamidated amino acids, and phosphorylated sugars. In the present report we establish that chicken bone collagen contains gamma-glutamyl phosphate. This was accomplished by the isolation of tritiated alpha-amino-delta-hydroxyvaleric acid after reductive cleavage with NaB[3H]H4 of the gamma components, the alpha 2 chains, and peptides enriched in organic phosphorus that were derived from the alpha 2 chains. Tritiated alpha-amino-delta-hydroxyvaleric acid was not detected in any of the following unphosphorylated proteins after cleavage with NaB[3H]H4:albumin and lysozyme, the alpha 2 chains of several unmineralized tissues, and, most importantly, dephosphorylated alpha 2 chains of chicken bone collagen. The alpha 2 chain of chicken bone collagen is the first structural protein found to contain an acyl phosphate.

Animals↗
PubMed1978

Increased metabolic activity of rabbit articular cartilage in vitro.

The metabolic, histochemical and ultrastructural modifications induced in rabbit articular cartilage during in vitro incubation at 37 degrees C, for various periods (10 min to 18 h), using Krebs phosphate-glucose nutrient medium, were studied. It was found that after only 10 min of incubation, the chondrocytes increase their synthesis of matrix macromolecules for, at least, the next 6 h. This was suggested by: 1. Increased incorporation 35S-sulfate and 3H-glycine during the first 6 h of incubation. 2. An intensification of metachromasia, which also spread out into the superficial layer that is normally orthochromatic. Only the most superficial layer corresponding to one or two rows of the cells, retained its staining pattern throughout the incubation; 3. A rapidly acquired abundant rough endoplasmic reticulum, enlarged Golgi area and numerous newly synthesized proteoglycan molecules. This study poses fundamental questions about the mechanisms that regulate matrix synthesis by the chondrocytes.

Animals↗
PubMed1977

[Identification of 2 phosphorylated amino acids in chicken bone phosphoproteins].

Phosphoproteins of Chicken bone have been extracted by 0.5 M EDTA pH 7.5. Their amino acid composition was similar to that of phosphoproteins of other calcified tissues. The crude EDTA extract contained 80 to 90% proteins, only 70% of the total organic phosphorus was bound to the proteins. We have studied and identified two phosphorylated components. o-phosphoserine and o-phosphothreonine have been identified by amino acid analysis at pH 1.7 from a partial acid hydrolysate, and confirmed by the liberation of the parent amino acids after total hydrolysis. In addition, phosphorus was found equimolecular to both of them. The presence of these phosphorylated groups is important for an understanding of the role of these proteins in the mechanism of mineralization.

Animals↗