Showing papers on "Keratan sulfate published in 1977"

Isolated acid neuraminidase deficiency: A distinct lysosomal storage disease

Abstract: An 8-month-old female presented with coarse facies and hepatosplenomegaly at birth. Growth proceeded at an accelerated rate and mental development was normal. A pattern of dysostosis multiplex developed radiographically. Cytoplasmic inclusions consistent with lysosomal storage disease were demonstrated by electron microscopy in bone marrow, liver, and cartilage cells and in cultured skin fibroblasts. Assays of the fibroblasts revealed a specific deficiency of acid neuraminidase and 6-fold increase in intracellular bound sialic acid. An unidentified macromolecular compound rich in sialic acid was excreted in excessive amounts in the urine. The phenotype suggests defective degradation primarily of glycoproteins and possibly to a lesser extent of keratan sulfate and gangliosides.

The biosynthesis of glycosaminoglycans in normal rat liver and in response to experimental hepatic injury.

Abstract: The synthesis of glycosaminoglycans in slices from normal and acutely injured rat liver was studied. The rates of incorporation of [14C]-glucosamine into specific types of glycosaminoglycans varied markedly; nearly 90% was incorporated into a fraction containing predominantly heparan sulfate and far less if any heparin; about 9.5% was incorporated into chondroitin 4-and 6-sulfate, and only 0.2% of the radioactivity was found in hyaluronic acid. The rate of synthesis of a fraction having several of the characteristics of keratan sulfate comprised only 0.3% of the synthesis of total glycosaminoglycans. No [14C]hexosamine was incorporated into dermatan sulfate. Following acute hepatic injury, the synthesis of glycosaminoglycans was stimulated by 80 to 100%, and the proportions of various types changed. If calculated on the basis of the specific activity of the precursors of glycosaminoglycans, which was found to be strongly reduced in injured liver, the maximum enhancement of total glycosaminoglycan synthesis was 6.6-fold 5 days after onset of liver injury.

Macular corneal dystrophy. Studies of sulfated glycosaminoglycans in corneal explant and confluent stromal cell cultures.

Abstract: The inherited disorder macular corneal dystrophy (MCD), a localized corneal mucopolysaccharidosis, is currently thought to result from an inability to catabolize corneal keratan sulfate (keratan sulfate 1). As studies on isolated cells have provided insight into metabolic abnormalities in other inherited disorders, we investigated cultured corneal fibroblasts from 4 patients with MCD from several standpoints. Lines of corneal fibroblasts with MCD could not be distinguished from controls with cytochemical methods known to stain the naturally occurring accumulations. In contrast to cultured fibroblasts from patients with mucopolysaccharidoses Type I-H (Hurler syndrome) and Type II (Hunter syndrome), corneal fibroblasts from patients with MCD did not accumulate abnormal quantities of (35)S-sulfate-labeled glycosaminoglycans, but like normal corneal and cutaneous fibroblasts reached a state of equilibrium within 2 days. Also, the rate at which sulfated glycosaminoglycans were removed from cultured corneal fibroblasts in MCD by secretion and degradation more closely resembled that of normal cells than those with the systemic mucopolysaccharidoses. The secretion of sulfated glycosaminoglycans into the nutrient medium by corneal fibroblasts from patients with MCD occurred at a linear rate comparable to that of other cells studied. The aforementioned data, nonetheless, remain consistent with the hypothesis that MCD is an inherited disorder of keratan sulfate I (corneal keratan sulfate) catabolism, as isolated corneal fibroblasts in contrast to corneal explants synthesize little or no keratan sulfate in culture. In view of the latter, we also compared the profile of (35)S-labeled glycosaminoglycans produced by a corneal explant from a patient with MCD with that normally synthesized by human corneal explants. The latter synthesized and secreted a population of (35)S-sulfate-labeled glycosaminoglycans with properties of keratan sulfate. Considerably less material with these attributes was identified with the same analytic techniques in the cornea with MCD or in its surrounding medium after the abnormal cornea had been incubated under identical conditions. In addition to manifesting an impaired synthesis of corneal keratan sulfate-like material, the cornea with MCD produced a greater percentage of chondroitin-6-sulfate than normal. These findings suggest that the synthesis of corneal keratan sulfate and other glycosaminoglycans may be altered in MCD.

Macular Corneal Dystrophy Studies ofSulfated Glycosaminoglycans inCorneal Explant andConfluent Stromal Cell Cultures

Abstract: Theinherited disorder macular corneal dystrophy (.MCD), alocalized corneal mucopolysaccharidosis, iscurrently thought toresult fromaninability tocatabolize corneal keratan sulfate (keratan sulfate 1).Asstudies onisolated cells haveprovided insight intometabolic abnormalities inother inherited disorders, weinvestigated cultured corneal fibroblasts from4patients withMCD fromseveral standpoints. Lines ofcorneal fibroblasts withMCD could notbedistinguished fromcontrols withcytochemical methods knowntostain thenaturally occurring accumulations. Incontrast tocultured fibroblasts frompatients withmucopolysaccharidoses TypeI-H(Hurler syndrome) and TypeII(Hunter syndrome), corneal fibroblasts frompatients withMCD didnot accumulate abnormal quantities of"S-sulfate-label ed glycosaminoglycans, butlike normal corneal andcutaneous fibroblasts reached astate ofequilibrium within 2days. Also, therateatwhichsulfated glycosaminoglycans wereremoved fromcultured corneal fibroblasts inMCD bysecretion anddegradation moreclosely resembled that ofnormal cells thanthose withthesystemic mucopolysaccharidoses. Thesecretion of sulfated glycosaminoglycans into thenutrient mediumbycorneal fibroblasts frompatients with MCD occurred atalinear ratecomparable tothat ofother cells studied. The aforementioned data, nonetheless, remain consistent withthehypothesis that MCD is aninherited disorder ofkeratan sulfate I(corneal keratan sulfate) catabolism, as isolated corneal fibroblasts incontrast tocorneal explants synthesize little ornokeratan sulfate inculture. Inviewofthelatter, wealso compared theprofile of'S-labeled glycosaminoglycans produced byacorneal explant fromapatient withMCD withthat normally synthesized byhumancorneal explants. Thelatter synthesized andsecreted a population of'5S-sulfate-labeled glycosaminoglycans withproperties ofkeratan sulfate. Considerably less material withthese attributes wasidentified withthesame analytic techniques inthecornea withMCD orinitssurrounding mediumafter the abnormal cornea hadbeenincubated under identical conditions. Inaddition tomanifesting animpaired synthesis ofcorneal keratan sulfate-like material, thecornea with MCD produced agreater percentage ofchondroitin5-6sulfate thannormal. These findings suggest that thesynthesis ofcorneal keratan sulfate andother glycosaminoglycans maybealtered inMCD.(AmJPathol 89:167-182, 1977)

Keratan sulfate proteoglycans.

Abstract: Summary of PhD thesis in biochemistry (physiological chemistry). (The 6 papers were cited 628 times 1974-2004.)

Combined action of protein-chondroitin-4-keratan-sulfate and hyaluronic acid on aggregation and adhesion of red cells

Abstract: The rate and degree of aggregation of red cells produced by a mixture of protein-chondroitin-4-keratan-sulfate (PCKS) and hyaluronic acid (HUA) were found to be greater than the sum of the values of the corresponding indices for the separate action of these proteoglycans on red cell aggregation in the same concentrations as in the mixtures. It is suggested that this effect is due to the formation of a hybrid PCKS-HUA complex in the mixture which is more accurate as regards red cell aggregation than the separate components.