SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
One of the neutral glycosphingolipids isolated from dog intestine has a mobility on thin-layer chromatography and a carbohydrate composition similar to trihexosylceramides. Structural analysis has shown that it consists largely of isoglobotriaosylceramide, galactosyl(alpha-1-3)galactosyl(beta-1-4)glucosyl(beta 1-1')ceramide.
Trihexosylceramide, isolated from human kidney and labelled in the terminal galactose position by oxidation with galactose oxidase and reduction with sodium boro[3H]hydride, was used to study some of the properties of human leucocyte alpha-galactosidase. The enzyme was inactive in the absence of detergent. Of all the detergents tested a crude sodium taurocholate preparation displayed the greatest activity. The optimal detergent concentration varied from 2 to 4 mg/ml depending on the protein concentration and indicating that the enzyme activity was dependent on the protein/detergent ratio. Because of its influence in regulating enzyme activity, it is essential that care must be taken to ensure that the protein/detergent ratio of all incubation mixtures is kept relatively constant whenever the diagnosis of Fabry's disease is attempted.
We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.
An immunofluorescence method was applied to detect trihexosylceramide accumulated in the cardiac tissues from a variant hemizygote and a heterozygous female with Fabry disease, the incidence of which had been suspected to be high.
The mechanism for the synthesis of Forssman glycolipid (GalNAc-alpha-GalNAc-beta-Gal-Gal-Glc-Cer) from trihexosylceramide (Gal-Gal-Glc-Cer, Hex3Cer) and radioactively labeled UDP-N-acetylgalactosamine catalyzed by particulate beta- and alpha-N-acetylgalactosaminyl-transferase of hamster NIL-2K cells was studied. The radioactivity incorporated into the Forssman glycolipid using a mixture of Hex3Cer and globoside (GalNAc-beta-Gal-Gal-Glc-Cer) as the substrates was greater than that from each substrate singly. When the radioactive Forssman glycolipid from the mixed substrates was hydrolyzed with alpha-N-acetylgalactosaminidase, the ratio of 14C-labeled globoside to the liberated N-acetyl[14C]galactosamine was 0.38, indicating that Hex3Cer could serve as a substrate. From these results, the following hypothesis (baton pass model) is proposed. There exists an enzyme complex consisting of beta- and alpha-transferases in membranes. In this complex, it is not possible to saturate alpha-transferase with exogenous globoside; however, it can utilize a transient globoside synthesized from Hex3Cer. It thus appears that Forssman glycolipid is in part formed from Hex3Cer through this enzyme complex without the accumulation of the intermediate globoside. The abbreviations used are: GalNAc, N-acetylgalactosamine; Cer, ceramide.
A new sulfated glycosphingolipid containing N-acetylglucosamine has been isolated from hog gastric mucosa by extraction with sodium acetate. Based on the results of partial acid hydrolysis, sequential degradation with specific glycosidases, and methylation analysis of the native and desulfated compound, the structure of this glycolipid is proposed to be: SO3H(leads to 6)GlcNAc-(beta 1 leads to 3)Gal(beta 1 leads to 4)Glc(1 leads to 1)Cer(GlcNAc, N-acetylglucosamine; Cer, ceramide).
Explore the source record for details and available documents.
This paper deals with the various crystalline aspects of the ceramide trihexoside (CTH) inclusions, in the synovial tissue essentially. A basic classification is proposed and uncommon examples are illustrated. Image processing confirms the membrane-like structure of CTH inclusions and corroborates the proposed classification.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have investigated the content and composition of neutral glycosphingolipids (GSLs) in the cells isolated by enzyme digestion from elastic-hyperplastic and musculo-elastic intimal layers of grossly normal and atherosclerotic regions of human aorta. We have detected three types of neutral GSLs in the intimal cells identified as glucosylceramide, trihexosylceramide and tetrahexosylceramide. We failed to detect lactosylceramide in the intimal cells. The cells of the elastic-hyperplastic layer of grossly normal regions contained trihexosylceramide and tetrahexosylceramide, while glucosylceramide was not detected. Considerable amounts of glucosylceramide were found, and the trihexosylceramide and tetrahexosylceramide content was increased in the cells isolated from atherosclerotic regions. The cells of the musculo-elastic layer of grossly normal intimal regions contained glucosylceramide, trihexosylceramide and tetrahexosylceramide. Cells of the musculo-elastic layer of the fatty streak contained noticeable higher amounts of glucosylceramide, as well as greater amounts of trihexosylceramide and tetrahexosylceramide. Cells of the musculo-elastic layer of the plaque also appeared to contain more glucosylceramide, tetrahexosylceramide, but less trihexosylceramide as compared with grossly normal regions. In both cases cells of the fatty streak exhibited the highest total amount of neutral GSLs, but at the same time the neutral GSL composition of the fatty streak was not similar to GSL composition which is known for human blood monocytes. These findings indicate that elevation of neutral GSL level is observed in cells from atherosclerotic lesions of human aortic intima.
Previous studies from this laboratory have demonstrated a striking difference in rat intestinal glycolipids between differentiated villus cells and immature crypt cells. Villus cells contained proportionally greater amounts of glucosylceramide and hematoside while crypt cells were deficient in hematoside, but contained proportionally greater amounts of trihexosylceramide. In order to further elucidate possible differences between villus and crypt cell glycolipids, a study of the sphingosine and fatty acids of rat intestinal glycolipids was conducted. Villus and crypt cells were separated from rat intestine and the glycolipids purified. Fatty acids and long chain bases of the three major glycolipids (glucosylceramide, trihexosylceramide, hematoside) extracted from these cells were characterized. Phytosphingosine accounted for 63-73% of the total long chain bases in all glycolipids whether from villus or crypt cells. Hydroxy fatty acids represented 70% of total fatty acids in the glucosylceramide and in the hematoside but accounted for only 30% in the trihexosylceramide. In addition, trihexosylceramide contained a larger percentage of fatty acids with 20-carbon atoms than glucosylceramide and hematoside isolated from villus cells. These fatty acids were more concentrated in crypt cells than in villus cells glycolipids. These results suggest that hematoside and trihexosylceramide, respectively abundant in villus and in crypt cells, may be derived from a different lactosylceramide precursor and further underscore differences in villus and crypt cell glycolipid synthesis.
Surface-exposed glycolipids in human platelets were investigated with nonpenetrating membrane probes, NaB3H4/galactose oxidase and NaB3H4/periodate. Trihexosylceramide, globoside, and hematoside were exposed in resting platelets. The incubation of platelets with thrombin resulted in a 50% reduction in the labeling of both trihexosylceramide and globoside and a 100% increase in labeling of hematoside on the platelet surface. The quantitation of glycolipids in platelets incubated with thrombin revealed no changes in the amounts of trihexosylceramide and globoside but there was an increase in hematoside. These experiments indicate that there is a specific rearrangement of glycolipids on the surface of thrombin-treated platelets. The study also showed that both ceramide A and B are present in platelets. The former contained 3.36 nmol of sphingosine and the latter 0.12 nmol of sphingosine/10(9) platelets. The sphingosine composition of ceramide B, glucosylceramide, and the minor platelet gangliosides was similar and they were composed of two-thirds erythrosphingosine (18:1) and one-third threosphingosine (18:1). The composition of lactosylceramide, trihexosylceramide, globoside, and hematoside was related to ceramide B and they contained about 60% erythrosphingosine (18:1), 25% threosphingosine (18:1), and 10% dihydrosphingosine (18:0). Ceramide A differed in that it was composed of 56% erythrosphingosine (18:1), 34.7% dihydrosphingosine (18:0), 4.3% threosphingosine (18:1), 2.7% erythrosphingosine (16:1), and 2.3% erythrosphingosine (17:1). The sphingosine composition of sphingomyelin resembled that of ceramide A but did not contain threosphingosine (18:1). The possibility that platelet ceramide B is involved n glycolipid metabolism and ceramide A in sphingomyelin metabolism is considered.
In a patient with Fabry's disease who had undergone kidney transplantation to correct uremia, the neutral glycosphingolipids and alpha-galactosidase activity have been measured in plasma and urine and, 9 months later, after the death of the patient, in autopsy material. After transplantation, there was no significant increase in alpha-galactosidase activity in plasma; the activity found never exceeded 3% of the mean control value. A striking parallelism was found during the follow-up period in the increase and decrease of trihexosylceramide and globoside and also of glucosylceramide and dihexosylceramide. The alpha-galactosidase activity in spleen and liver was as low as that observed in untreated Fabry hemizygotes. These data and those obtained from autopsy material provide evidence that renal transplantation does not lead to a specific enzymic breakdown of trihexosylceramide in Fabry patients. However, no trihexosylceramide accumulation was observed in the transplanted kidney.
Previous studies have suggested that glycosphingolipids may be involved in a number of physiological functions of the small intestinal mucosa. Regional variations in many of these processes exist along the length of this organ. In the present studies, the glycosphingolipid and ceramide composition of the proximal, middle and distal thirds of the rat small intestine were characterized and compared. Mono- and trihexosylceramide were the major neutral glycolipids and hematoside (GM3), the principal ganglioside of this organ. Monohexosylceramide was the major glycolipid of the proximal segment, whereas trihexosylceramide predominated in the distal segments. The total content of neutral glycolipids, ceramide and gangliosides as well as the content of the individual glycosphingolipids and ceramide were highest in the distal segment, intermediate in the middle and lowest in the proximal segment. Additionally, regional variations were noted in the fatty acid composition of the major glycosphingolipids. These differences in the composition of glycolipids and ceramide along the length of the intestine may be responsible, at least partially, for the regional functional specialization seen in this organ.
The activation of sphingomyelinase, galactosyl- and lactosylceramide beta-galactosidases, GM1, beta-galactosidase, cerebroside sulphate sulphatase, trihexosylceramide alpha-galactosidase and globoside beta-hexosaminidase by a number of bile salts was studied. Most of the salts examined, except glycolithocholate and deoxycholate, were effective activators of enzyme activity. Pure, but not crude, taurocholate elicited poor trihexosylceramide alpha-galactosidase and cerebroside sulphate sulphatase activities. The bile salt activation was often dependent on a number of parameters including the bile salt concentraion, pH, protein to bile salt ratio, and the nature of the enzyme preparation. In the absence of bile salts, Triton X-100 induced little activity of any of the hydrolases except sphingomyelinase; in their presence however, Triton either promoted or inhibited the activation depending on the enzyme. Our data suggest that bile salt structure is an important factor in determining the degree of activation of individual hydrolases and that this may be due to intramicellar lipid substrate/bile salt interactions, which either facilitate or inhibit the corresponding enzyme reaction.