Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a report on a stored lipid atypical ultrastructural pattern in skin samples of Fabry's disease expressed exclusively in the endothelium. The pattern consisted of intersecting short crescentic tightly packed membranes with a periodicity identical to that in classical ultrastructural variants. At low magnification the lysosomal aggregates of the material resembled "sunbursts" or aggregates of densely packed squirming villus-like structures. According to results of ultrastructural, lipid, and lectin histochemical analyses including analysis of the patients' blood groups, it could be concluded that it is just a variant physical state of the otherwise typical Fabry lipid. Its origin could be attributed to impeded formation (or maintenance) of larger lipid lamellae. It was found in great amounts in skin capillaries in 2 cases, and rarely in 5 additional cases. Knowledge of this atypical ultrastructural pattern is of practical significance because it could, if prevalent, cause diagnostic problems.
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PMID:An atypical ultrastructural pattern in Fabry's disease: a study on its nature and incidence in 7 cases. 212 6

The presence of an alpha-galactolipid was investigated with a peroxidase-labelled lectin from Griffonia simplicifolia (GSA-I) with specific binding for terminal alpha-D-galactose residues. Normal kidney tissue was obtained from patients undergoing nephrectomy for renal neoplasms. For light microscopy, tissue was snap-frozen; 4 microns-thick sections were briefly fixed in paraformaldehyde and incubated with GSA (0.025 mg ml-1). The peroxidase activity was developed with 3-amino-9-ethylcarbazole. Adjacent sections were stained at the same time after lipid extraction with 3:1 (v/v) chloroform/methanol. For electron microscopy, 0.2-0.5 mm-thick paraformaldehyde-fixed blocks, with or without lipid extraction, were stained with peroxidase-labelled GSA. The label was developed with diaminobenzidine and osmium tetroxide. Some structures, such as tubular epithelia, stained both in lipid-extracted and non-extracted tissues, suggesting that glycoproteins were most likely involved. In addition, tissue stained immediately after fixation showed GSA reactivity on endothelial cell surfaces of intertubular capillaries and larger vessels. In lipid-extracted tissues, however, tubular epithelium was still positive for GSA but endothelial cells failed to stain. These findings suggest that a glycolipid, bearing a terminal alpha-galactose residue, is present on the endothelial cells in human kidney and possibly on tubular epithelia. Our data may explain the preferential storage of alpha-galactolipid in endothelial cells of patients with Fabry's disease and other biological phenomena such as Escherichia coli adhesion.
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PMID:Presence of an alpha-galactolipid on the cell surfaces of endothelial cells of human kidney. 267 70

Endothelial cells are of particular interest for therapeutic strategies in Fabry's disease, because the accumulation of glycosphingolipids in the vascular endothelium as a result of alpha-galactosidase A (alpha-galA) deficiency is responsible for the major clinical manifestations of the disease. Electron microscopical observations of cultured endothelial cells obtained from the umbilical vein of a hemizygous Fabry fetus showed that the glycosphingolipids are deposited as lamellar material in the lysosomes, as has been found previously for cultured fibroblasts and many different tissues. Mannose 6-phosphate (man 6-P)-receptor mediated and Concanavalin A (ConA)-mediated uptake of purified alpha-galA was attempted in the endothelial cells as well as in cultured fibroblasts from the same fetus. Our results on high-uptake alpha-galA indicate that the endothelial cells do not internalize alpha-galA via the man 6-P receptor. Immunofluorescence studies after addition of the receptor antibody to the cells support the theory that they have no or very few man 6-P receptors on the surface. Morphological studies did not show lysosomal changes which could suggest that the enzyme is taken up into the endothelial cells; however, we found reproducible modifications of the lysosomes in Fabry fibroblasts after incubation with high-uptake alpha-galA. Cell-associated alpha-galA activity was found in both cell types, when the enzyme was added to cells preincubated with ConA; but the lectin treatment by itself induced considerable ultrastructural changes in the cytoplasm, which obscured a possible effect by the enzyme.
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PMID:Enzyme replacement in Fabry endothelial cells and fibroblasts: uptake experiments and electron microscopical studies. 283 53

Kidney and liver samples from two cases of Fabry's disease and spleen and liver samples from Gaucher and Niemann-Pick diseases were tested for binding to lectins such as peanut agglutinin (PNA), Bandeiraea simplicifolia, (BSA), canavalia ensiformis (Con A), soybean agglutinin (SBA) and wheat germ agglutinin (WGA) labelled with horseradish peroxidase using histochemical techniques. These techniques allowed the localization of compounds with alpha-galactosyl residues in tissues from Fabry's disease. In tissues from the Gaucher and Niemann-Pick cases, the storage material was found to be more complex than expected, and some problems regarding the significance of lectin binding are discussed.
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PMID:Characterization by lectin binding of the sugar moiety of glycocompounds stored in inherited diseases. 312 29

Fabry disease is an X-linked inherited metabolic disorder that is caused by a deficiency of alpha-galactosidase A (alpha-Gal A). Progressive deposition of neutral glycosphingolipids that have terminal a-linked galactosyl moieties in vascular endothelial cells causes renal failure along with premature myocardial infarctions and strokes in patients with this condition. No specific treatment is available for patients with this disorder at this time. An animal model of this condition would be valuable for exploring therapeutic strategies for patients with Fabry disease. We report here the generation of alpha-Gal A deficient mice by gene targeting and an analysis of the resulting phenotype. The knockout mice display a complete lack of alpha-Gal A activity. The mice, however, appeared clinically normal at 10 weeks of age. Ultrastructural analysis revealed concentric lamellar inclusions in the kidneys, and confocal microscopy using a fluorescent-labeled lectin specific for alpha-D-galactosyl residues showed accumulation of substrate in the kidneys as well as in cultured fibroblasts. Lipid analysis revealed a marked accumulation of ceramidetrihexoside in the liver and the kidneys. These findings indicate the similarity of the pathophysiological process in the mutant mice and in patients with Fabry disease. The deficiency of alpha-Gal A activity and the accumulation of material containing terminal alpha-galactosyl residues in cultured embryonic fibroblasts derived from alpha-Gal A(-/0) mice were corrected by transducing these cells with bicistronic multidrug resistance retroviruses containing human alpha-Gal A cDNA.
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PMID:alpha-Galactosidase A deficient mice: a model of Fabry disease. 912 31

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from a deficiency of lysosomal alpha-galactosidase activity. Globotriaosylceramide accumulates predominantly in lysosomes of various tissues. Former studies have clarified the nature of this disease, and the accumulated materials in the lysosomes have been analyzed using biochemical techniques. In the present study, transmission electron microscopy was used to reveal the fine structure of these lysosomal deposits, and sugar residues in the lysosomal deposits in Fabry disease were examined by lectin histochemistry combined with enzyme digestion. This is the first report to describe the lysosomal sugar residues in Fabry disease analyzed using lectin histochemistry at the ultrastructural level. With these techniques, we were able to detect alpha-galactosyl, beta-galactosyl and glucosyl sugar residues in the lysosomal deposits. The experimental procedures used in this study have considerable potential for use in investigations of glycolipid and glycoprotein storage diseases without the need for complex methodology and expensive materials.
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PMID:Fabry disease: ultrastructural lectin histochemical analyses of lysosomal deposits. 1066 60