Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corneal buttons were obtained from patients with types 1 and 2 macular corneal dystrophy (MCD) and from control patients with Fuchs' dystrophy or keratoconus. Buttons were incubated for 20 h in the presence of [3H]glucosamine or [2-3H]mannose. Radiolabeled proteoglycans and lactosaminoglycan-glycoproteins (L-GPs) were purified using chromatography on Q-Sepharose, Superose 6, and octyl-Sepharose. They were identified using chondroitinase ABC, keratanase or endo-beta-galactosidase digestion, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis or Superose 6 chromatography. This study confirms previous reports that type 1 MCD corneas synthesize a normal dermatan sulfate-proteoglycan (DS-PG) and an abnormal keratan sulfate-proteoglycan (KS-PG). The data indicate that typ 1 MCD corneas synthesize L-GP instead of KS-PG. This L-GP has a core protein of similar hydrophobicity (elution from octyl-Sepharose) and nearly similar mass (42 kDa) as the core protein of the KS-PG. It has identical glycoconjugates as those of the KS-PG except that they lack sulfate. Thus, type 1 MCD fails to synthesize keratan sulfate as a result of a defect in a sulfotransferase specific for sulfating lactosaminoglycans. Further, proteoglycans synthesized by a cornea from a patient with type 2 MCD were studied. This cornea synthesized a normal ratio of KS-PG to DS-PG although net synthesis of proteoglycans was approximately 30% below normal. The KS-PG appeared normal whereas the DS-PG had dermatan sulfate chains that were approximately 40% shorter than normal.
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PMID:Proteoglycan biosynthesis by human corneas from patients with types 1 and 2 macular corneal dystrophy. 239 54

The distribution of sulphated proteoglycans within the stromas of three patients (A,B,C) suffering from macular corneal dystrophy was studied using the specific dye Cuprolinic Blue in a 'critical electrolyte concentration' method. The corneas were examined using transmission electron microscopy and A and C were further studied by low-angle synchroton X-ray diffraction. Sera from all three patients were analyzed for the presence of keratan sulphate using a monoclonal antibody in an enzyme-linked immunosorbent assay. The serum from Patient A contained keratan sulphate, but the chains were thought to be shorter or less sulphate in their sera. Electron microscopy showed many electron-transparent lacunae randomly distributed throughout the specimens. The average collagen fibril diameter was normal but there were differences in packing between the specimens. Specimen A was closely-packed with most collagen fibrils in contact with their neighbours. Specimens B and C showed fewer regions of close packing; in most of the tissue the interfibrillar spacing appeared normal. Staining with Cuprolinic Blue revealed an unusual distribution of proteoglycans in some parts of the interfibrillar matrix, particularly in A, with 'small' proteoglycans running exclusively parallel to the collagen fibrils. Furthermore in A, and to a lesser extent in B and C, some lacunae were filled with clusters of abnormal sulphated proteoglycan filaments (of various sizes) which were chondroitinase ABC susceptible. Clearly defined regions, both within the lacunae and elsewhere, failed to stain with Cuprolinic Blue; this suggests an absence of sulphated proteoglycans within these areas. Equatorial X-ray diffraction of the wet tissues (A and C) gave values for the mean interfibrillar centre-to-centre separation of 43 +/- 2 nm in Specimen A and 52 +/- 3 nm in Specimen C. The differences observed in the serum keratan sulphate levels, the packing of the collagen fibrils and the distribution of chondroitin/dermatan sulphate proteoglycans confirm the heterogeneity that exists within the macular corneal dystrophies.
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PMID:Macular corneal dystrophy: the macromolecular structure of the stroma observed using electron microscopy and synchrotron X-ray diffraction. 251 72

Synchrotron x-ray diffraction patterns from macular corneal dystrophy (MCD) corneas contain an unusual reflection that arises because of an undefined ultrastructure with a periodic repeat in the region of 4.6 A. In this study, we compared with wide-angle x-ray diffraction patterns obtained from four normal human corneas and four MCD corneas. Moreover, portions of two of the MCD corneas were pretreated with a specific glycosidase to shed light on the origin of the 4.6 A reflection. None of the normal corneas produced an x-ray reflection in the region of 4.6 A, whereas all four of the MCD corneas did (MCD type I at 4.65 A and 4.63 A, MCD type II at 4.63 A and 4.67 A). This reflection was diminished after incubation of the MCD tissues with either chondroitinase ABC or N-glycanase. The findings indicate that glycosaminoglycans or proteoglycans contribute to the unusual MCD x-ray reflection and hence most likely contain a periodic 4.6 A ultrastructure. Furthermore, the results imply that periodic 4.6 A MCD ultrastructures reside in either intact, unsulfated lumican molecules and regions of the CS/DS-containing molecules or in a region of a hybrid macromolecular aggregate formed by the interaction of the two molecules.
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PMID:Proteoglycans contain a 4.6 A repeat in muscular dystrophy corneas: x-ray diffraction evidence. 878 55

We investigated an individual macular corneal dystrophy (MCD) type II cornea from a 42-year-old woman with markedly reduced antigenic keratan sulphate levels. A characteristic 4.6 A X-ray reflection was evident, and the mid-stroma contained 30% less sulphur than normal. Close packing of collagen was restricted to the superficial stroma. Abnormally large proteoglycan filaments were noted throughout the extracellular matrix and Descemet's membrane's posterior non-banded zone, but not its anterior banded zone. Small, collagen-associated stromal proteoglycans were susceptible to digestion with chondroitinase ABC, but not keratanase I or N-glycanase. On occasion, collagen fibrils ranged in size from 20 nm to 58 nm, with preferential diameters of 34 nm and 42 nm. Corneal guttae were evident, as were numerous endothelial inclusions, most probably due to intracellular fibrillogranular vacuoles similar to those found in the stroma. The endothelium expressed reduced anti-keratan sulphate labelling.
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PMID:Macular corneal dystrophy type II: multiple studies on a cornea with low levels of sulphated keratan sulphate. 924 78