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Biomedical subjects

D R Eyre

Publications and source records attributed to D R Eyre.

At least 127 records · Page 7Linked to original sources
PubMed1982

Collagen polymorphism in extracellular matrix of human osteosarcoma.

The collagenous matrix of human osteosarcoma was characterized biochemically and ultrastructurally. The highly cellular regions of the tumors contained many osteoblast-like cells filled with dilated rough endoplasmic reticulum. The extracellular matrix displayed a random weave of banded collagen fibrils (30--90 nm in diameter) interspersed with thinner, unbanded fibrils (15 nm in diameter). Tumors from 9 patients were analyzed for collagen composition. All gave a similar collagen profile. Three main molecular species of collagen were abundant: type I, type III, and type V, which occurred in the approximate proportions of 65:25:10. A high ratio of alpha 1(I) to alpha 2(I) chains suggested that one-third of the type I collagen was present as a type I trimer molecule. In contrast, normal bone matrix consisted almost exclusively of type I collagen. The fibrillar collagens in the soft tumor seemed unusually rich in hydroxylysine and hydroxylysine glycosides; type I collagen had two to three times the hydroxylysine content of normal bone collagen.

Adolescent↗
PubMed1981

Concepts in collagen biochemistry: evidence that collagenopathies underlie osteogenesis imperfecta.

Collagen, the principal structural macromolecule of the body, is expressed as a family of genetically distinct protein molecules. Two main subfamilies are emerging, the interstitial, fibrillar collagens (Types I, II and III) and the cell-associated or basement membrane collagens (Types IV and V). All types are synthesized as precursor molecules of procollagen, which are trimmed by specific proteases to form the subunit of extracellular fibrils. Evidence is accumulating that the osteogenesis imperfecta group of diseases are inherited molecular pathologies of Type I collagen, the commonest collagen type. However, a variety of biochemical lesions are anticipated, in part because of the marked clinical heterogeneity of the disorder. For example, in one variant a defect is becoming evident in the primary structure of Type I procollagen which seems to inhibit its rate of secretion from the cell. In another, there is evidence of complete failure to express the collagen alpha 2 chain, a disorder perhaps analogous to the thalassemia syndromes of hemoglobin pathology.

Chemical Phenomena↗
PubMed1980

Collagen type II differs from type I in native molecular packing.

Native molecular packing of types I and II collagens were compared by low-angle X-ray diffraction. Fibers from human intervertebral disc that contained different proportions of types I and II collagens were studied by X-ray diffraction, and were then analyzed biochemically to measure the constituent collagen species. Other cartilages, containing exclusively type I or type II collagen, were also examined. The equatorial diffraction established that in wet, native type II collagen, the molecules are spaced farther apart laterally than in type I collagen under the same conditions. For the disc the average lateral spacing ranged from about 14 A for a fiber from the outer annulus fibrosus containing mostly type I collagen, to 16-17 A for nucleus pulposus that contained all type II collagen. No differences were evident among dried specimens. We have also found that the meridional diffraction pattern from dry fibers of type II collagen differed from that of type I collagen. The findings indicate that under physiological conditions type II collagen fibrils contain more water than type I fibrils. Calculations suggest 50-100% more water. We propose that this difference is an inherent property of type II collagen and that it may be significant for the function of type II collagen in tissues that dissipate compressive forces. The content of glycosylated hydroxylysine residues is the chemical variable likely to be modulating fibrillar hydration.

Adolescent↗
PubMed1980

Biosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthrosis.

Osteoarthrosis was induced in one knee joint of dogs by an established surgical procedure. Changes in the articular cartilage in the biosynthesis of collagen and other proteins were sought by radiochemical labelling in vivo, with the following findings. (1) Collagen synthesis was stimulated in all cartilage surfaces of the experimental joints at 2, 8 and 24 weeks after surgery. Systemic labelling with [3H]proline showed that over 10 times more collagen was being deposited per dry weight of experimental cartilage compared with control cartilage in the unoperated knee. (2) Type-II collagen was the radiolabelled product in all samples of experimental cartilage ranging in quality from undamaged to overtly fibrillated, and was the only collagen detected chemically in the matrix of osteoarthrotic cartilage from either dog or human joints. (3) Hydroxylysine glycosylation was examined in the newly synthesized cartilage collagen by labelling dog joints in vivo with [3H]lysine. In experimental knees the new collagen was less glycosylated than in controls. However, no difference in glycosylation of the total collagen in the tissues was observed by chemical analysis. (4) Over half the protein-bound tritium was extracted by 4 M-guanidinium chloride from control cartilage labelled with [3H]proline, compared with one-quarter or less from experimental cartilage. Two-thirds of the extracted tritium separated in the upper fraction on density-gradient centrifugation in CsCl under associative conditions. Much of this ran with a single protein band on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis under reducing conditions. The identity of this protein was unknown, although it resembled serum albumin in mobility afte disulphide-bond cleavage.

Animals↗
PubMed1980

Collagen: molecular diversity in the body's protein scaffold.

Intensive research in the last decade has revealed a wealth of detail on the mechanism of biosynthesis, molecular structure, and covalent cross-linking of collagen. Tissues of higher animals express a family of at least five genetically distinct types of collagen molecule, each apparently tailored for different construction work outside the cell. Within each genetic type of collagen, further chemical heterogeneity is also evident; the variations in hydroxylation, glycosylation, and cross-linking are dependent, for example, on tissue type, age, and hormonal status. The functional significance of collagen's molecular diversity and its control by different cells and tissues are not yet well understood but abnormalities of collagen in many human diseases keep this protein a focal molecule of medical research.

Amino Acid Sequence↗
PubMed1980

Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee.

UNLABELLED: Wounds penetrating articular cartilage to bone heal with cartilage described variably as either fibrous or hyaline. In the present study, such repair cartilage was induced in the rabbit for biochemical comparison with normal articular cartilage. The main collagen in the repair tissue after three weeks was type I. By six to eight weeks, type II had become predominant and continued to be enriched up to one year; but type I still persisted as a significant constituent of the repair tissue even after a year, so the repair cartilage never fully resembled normal articular cartilage. From radiochemical analysis, type II was determined to be the major collagen synthesized by the repair tissue after three to four weeks. After six months, the repair cartilage contained more collagen and less hexosamine than control cartilage, suggesting that the fibrous texture that often developed was due to a loss of proteoglycans rather than to a change in the type of collagen. CLINICAL RELEVANCE: Procedures capable of inducing the differentiation of authentic articular cartilage to resurface degenerated human joints would be invaluable. Surgical methods, such as drilling through to subchondral bone, are often attempted. It is not known, however, whether the cartilage that forms is true articular cartilage or, for example, fibrocartilage. The present experimental study in rabbits compared the properties of such repair cartilage with those of normal articular cartilage.

Animals↗
PubMed1980

Changes in tissue morphology and collagen composition during the repair of cortical bone in the adult chicken.

UNLABELLED: An animal model was developed to study the histology and collagen chemistry of healing cortical bone. A hole was cut through the cortex of the mid-shaft of the humerus of the adult chicken, which allowed for repair at a mechanically stable site. After one to two weeks the collagen of the repair tissue, which consisted principally of woven bone, contained almost three times as much hydroxylysine as the collagen of normal adult bone and thus resembled the collagen of embryonic long bones. By eight weeks, when lamellar one predominated, the hydroxylysine content had fallen to normal levels. Type I was the major genetic type of collagen present throughout. No type-II collagen, characteristic of cartilage, was detected; this was consistent with the histological findings. The results established that hydroxylysine-rich type-I collagen can be made by osteoblasts of adult animals as well as by those of embryos and early postnates. CLINICAL RELEVANCE: In order to understand the biological characteristics of fracture healing, it is vital to study not only the macroscopic organization of the repair tissue but also the chemical properties of its molecular components. The strength of healing fractured bone, and indeed of normal bone, depends largely on the properties of the structural protein collagen. To date, it is not known whether the collagen in healing fractures is the same as that in normal bone, or whether it has distinct chemical features that may suit it for bone repair.

Animals↗
PubMed1977

Biochemical aspects of development and ageing of human lumbar intervertebral discs.

Nucleus pulposus and annulus fibrosus from individual normal discs of different ages have been separately examined, and the topographical distribution of constituents across the annulus fibrosus has been determined. Collagen content, including the molecular species, and proteoglycans have been estimated. Type I collagen was found in the outermost regions of the annulus and type II in the innermost, whereas the nucleus contained type II collagen. In older spines the collagen content of the annuli increased both outwards in the disc, and downwards along the spinal levels. Proteoglycan content was higher in the nucleus, and the proportion of keratan to chondroitin sulphate increased with age, as did the hyaluronate content. It is concluded that differences in mechanical function may be reflected by differences in chemical composition of the discs, and that mechanical failure could result from local variations in chemical composition.

Adolescent↗
PubMed1975

The distribution of different molecular species of collagen in fibrous, elastic and hyaline cartilages of the pig.

The distribution of type II collagen, considered to be characteristic of cartilaginous tissues, was determined in various specialized cartilages of the mature pig. The tissues examined were: (1) fibrocartilage of the semilunar meniscus of the knee; (2) elastic cartilage of the external ear; (3) hyaline cartilage of (a) the synovial joint (b) the thyroid plate of the larynx, and (c) the nasal septum. The predominant species of collagen in each tissue, whether type I or type II, was appraised semi-quantitatively by analysis of purified collagen solubilized by pepsin and of peptide fragments produced by cyanogen bromide. Cyanogen bromide-derived peptides were characterized by column chromatography on CM-cellulose and by electrophoresis in sodium dodecyl sulphate-polyacrylamide gels. The proportion of each type of collagen was determined precisely by isolating the homologous small peptides alpha1(II)CB6 [nomenclature of Miller (1973) Clin. Orthop. 92, 260-280], by column chromatography on phosphocellulose and determining their relative proportions by amino acid analysis. Thus collagen of the fibrocartilage of the meniscus proved to be all type I; type II was not detected. In contrast, collagen of elastic cartilage of the outer ear, after rigorous exclusion of perichondrium, was type II. Similarly, type II was the only collagen detected in all the mature hyalline cartilages examined.

Amino Acids↗