Search

SUMMARY A case of mucopolysaccharidosis is described, in which the principal glycosaminoglycan stored in the liver and excreted in the urine was chondroitin sulphate. Both isomers were present in equal amounts. The clinical features were similar to those of the Hurler syndrome or mucopolysaccharidoses type I (McKusick 1966). RESUME Une forme de mucopolysaccharidose avec surcharge viscerale et elimination urinaire excessive de chondroitine sulfate Les auteurs decrivent un cas de mucopolysaccharidose dans lequel le principal glycosaminoglycan stocke dans le foie et elimine dans les urines etait la chondroitine sulfate. Les deux isomeres etaient presents en quantiteegaie. Les symptomes cliniques etaient semblables e ceux du syndrome de Hurler autrement dit du type I des mucopolysaccharidoses selon la classification de McKusick en 1966. ZUSAMMENFASSUNG Eine Form von Mukopolysaccharidose, bei der Chondroitinsulfat in Organen gespeichert und in hohem Maβe in Urin ausgeschieden wird Es wird ein Fall von Mukopolysaccharidose beschrieben, bei dem von Glykoaminogly-kanen hauptsachlich das Chondroitinsulfat in der Leber gespeichert und im Urin ausgeschieden wurde. Beide Isomeren waren in gleichem Mase vertreten. Das klinische Bild ahnelte dem beim Hurler Syndrom oder bei der Mukopolysaccharidose Typ I, wie auch von McKusick 1966 berichtet wurde. RESUMEN Una forma de mucopolisacaridosis con almacenamiento visceral y excesiva excrecion urinaria de condroitin sulfato Se describe un caso de mucopolisacaridosis en que el principal acumulo de glicosamino-glican en el higado y excretado en orina era el condroitin sulfato. Ambos isomeros estaban presentes en cantidades iguales. Los caracteres clinicos eran similares a los del sindrome de Hurler o mucopolisacaridosis tipo I descrita por McKusick en 1966.

Chondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico-chemical properties of cartilage-specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage-specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage-specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.

The release rates of specific components of the proteoglycan aggregates (G1 domain, the chondroitin sulfate and keratan sulfate containing portion of the protein core, and link protein) of the articular cartilage of mature beagles were studied at early stages of canine experimental osteoarthritis (OA), generated by transection of the anterior cruciate ligament. Analysis of cartilage explants and synovial fluids indicates that at early stages of experimental OA, there is increased release of the proteoglycan aggregates of the articular cartilage. This involves a release from the tissue of the components of the proteoglycan that are specifically involved with aggregation together with the glycosaminoglycans of the proteoglycan. These components were detected at elevated levels in the media of explants of cartilage from the operated joint, and in the synovial fluids of the operated joints.

Monomer and aggregated proteoglycans were prepared from pig laryngeal cartilage. Vascoelastic flow properties, comprising linear complex dynamic shear modulus, nonlinear steady-state shear-rate dependent viscosity, and primary normal stress difference, were measured in proteoglycan solutions containing varying proportions of aggregate (0-80%) and at different concentrations (10-50 mg/ml). Results were analyzed using the simple Oldroyd four-parameter nonlinear rate-type rheological equation. All solution properties were strongly dependent on proteoglycan concentration and on the proportion of aggregates present. Aggregation was found to have a great effect on the zero shear-rate viscosity at 50 mg/ml, which increased fivefold from 0-100% aggregate. The results showed that network formation in proteoglycan solutions increased with concentration from 10-50 mg/ml and also increased with aggregation. All proteoglycan solutions showed shear thinning, which was most marked with aggregated proteoglycan at high concentration (50 mg/ml), where the viscosity decreased tenfold from the zero shear-rate limit to the infinite shear-rate limit. The intermolecular interactions in the network were therefore increasingly disrupted by increasing shear rate, but repeated measurements showed that these were reversible changes and that testing did not induce disaggregation or degradation of proteoglycan. These rheological properties show that aggregation is likely to immobilize proteoglycan at high concentration within cartilage and to contribute to the material properties of the porous solid matrix of articular cartilage that are important for its load-bearing function.

Although many studies have attempted to elucidate how cytotoxic T (Tc) lymphocytes cause the death of target cells, the mechanism is still controversial. In the present study the effect on the integrity of the lysosomes of the target cell has been investigated. We show here that the specific recognition and attachment of cloned type A influenza-specific Tc cells to A/X31 influenza virus-infected target cells caused rapid change in the amount of lysosomal naphthylamidase activity that was bound within the lysosomes, indicating that the lysosomal membianes in the target cells had been totally labilized. Target cells infected with type B influenza virus served as controls. We therefore suggest that the viral specificity of Tc, lymphocytes allows for recognition and intimate membrane contact with suitably infected targets. This intimate contact induces sufficient perturbation of the target cell plasma membrane so as to cause total labilization of the target cell lysosomes which could account for intracellular lysis.

Experimental intervertebral disc degeneration produced in rabbits by ventral nuclear herniation reliably produces vertebral osteophytes. Osteophytes arise from proliferating inner annular fibers which undergo metaplasia into cartilage, calcify, and proceed through an endochondral ossification sequence. Proteoglycans extracted from the osteophytes reveal that the degree of aggregation, molecular size of the monomer, and the chondroitin sulfate/keratin sulfate ratio are directly related to the cartilage state of the tissue.

The structure of newly synthesized proteoglycans from explant cultures of cartilage from joints subjected to transection of the anterior cruciate ligament (osteoarthritic) and from normal (non- or sham-operated) joints was examined. The structure of the products of proteoglycan turnover was also examined using explants of normal and osteoarthritic cartilage maintained in culture for a 48 h chase period. The findings were as follows: Newly synthesized (/sup 35/S)-proteoglycans extracted from cartilage explants from osteoarthritic joints whether examined 3 weeks, 3 months, or 6 months after surgery were larger than those from corresponding normal cartilage. This can be explained by the synthesis in osteoarthritic cartilage of abnormally long chondroitin sulfate chains on newly synthesised proteoglycans. The extracts also contained a newly formed small proteoglycan species that was unable to interact with hyaluronic acid. The proportion of this species was higher in osteoarthritic cartilage compared with normal, examined 3 weeks after surgery, but was generally absent from cartilage obtained 3 and 6 months after surgery. Compared with controls, a smaller proportion of the (/sup 35/S)-proteoglycans released into the maintenance medium of explant cultures of osteoarthritic cartilage during a 48 h chase period was able to interact with hyaluronic acid. However, although furnished withmore » longer (/sup 35/S)-glycosaminoglycan chains, these proteoglycans were smaller than those from control explants.« less

Proteoglycans in the matrix of adult cartilage are metabolised quite rapidly [ 1,2], nevertheless adult cartilage has a limited capacity for repair. Embryonic cartilage on the other hand, is able to replace the proteoglycans of the matrix within a few days after they have been largely depleted by the action of enzymes [3,4], which suggests that the macromolecules in the environment exert some influence over the synthetic or secretory functions of chondrocytes. The possible influence of a variety of macromolecules on the biosynthesis of sulphated glycosaminoglycans has therefore been examined using suspensions of nondividing adult chondrocytes, obtained from pig laryngeal and articular cartilage. Cartilage contains small amounts of hyaluronic acid [5], low concentrations of which have important biological effects [6]. The effect of low concentrations of hyaluronic acid on the incorporation of 35SOiinto material precipitable by cetylpyridinium chloride (CPC) is reported here.