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PubMed2000

Altered intercellular glycoconjugates and dilated intercellular spaces of esophageal epithelium in reflux disease.

BACKGROUND AND AIMS: The usefulness of histological diagnosis of gastroesophageal reflux disease (GERD) is limited by poor specificity or sensitivity of available diagnostic tools. Recently, ultrastructural morphometry showed interstitial space dilation (ISD) to be a reliable sign of reflux disease. Aims of this study were to (a) search for a light microscopy equivalent of ISD, (b) test its diagnostic value, and (c) look for a possible role of intercellular glycoconjugates in its genesis. METHODS: Esophageal grasp biopsies were taken during endoscopy, 2-3 cm and 6-7 cm above the squamocolumnar junction, from patients under investigation for GERD symptoms. The biopsies were fixed in aldehyde solutions and embedded in resin for electron microscopy or in paraffin for routine histology, and the glycoconjugates underwent immunohistochemistry using 3-fucosyl-N-acetylactosamine antibodies. RESULTS: Irregular intercellular space dilation was detected in the basal and prickle layers using both light and electron microscopy. Hematoxylin-eosin preparations showed ISD in 20 of 22 (90%) erosive esophagitis cases, 30 of 44 (68%) endoscopy negative GERD cases, and 1 of 12 (8%) controls, with good interobserver (K = 0.75) and bioptic site reproducibility. ISD correlated with loss or rearrangement of intercellular glycoconjugates of the overlying layers and with granulocyte (eosinophil and/or neutrophil) infiltration. CONCLUSIONS: Light microscopy ISD is a suitable index of GERD. Alterations of intercellular glycoconjugates are likely to have a role in the genesis of ISD and GERD.

Esophagus↗
PubMed2005

Morphology and glycoconjugate content of opossum esophageal epithelium and glands: regional heterogeneity and effects of acid-induced mucosal injury and recovery.

This study examined the regional heterogeneity and site-specific changes in histology and glycoconjugate content following the induction of esophagitis and after recovery in an established animal model. Esophageal samples were excised from five sites in anesthetized opossums 24 hr after 3 consecutive days of 45-min perfusion with saline or 100 mM HCl or 1 week after acid in recovery animals. Controls exhibited significant regional differences in epithelial thickness, gland volume, glycoconjugate composition, and mast cell numbers. Acid perfusion induced erosive esophagitis and significant epithelial denudation throughout the distal 7 cm, combined with significant site-specific increases in gland lumen volume, decreases in mast cell numbers, and changes in glycoconjugate content. No differences from controls were noted in recovery animals, except for a significant increase in epithelial thickness and change in glycoconjugate content in the distal 2 cm. The results of this study highlight the impact of acid exposure on these structural defenses, but further investigation is required to explore the importance of these acid-induced changes in the pathogenesis of reflux esophagitis.

Animals↗
PubMed1998

Anionic glycoconjugates from differentiated and dedifferentiated cultures of bovine articular chondrocytes: modulation by TGF-beta.

Primary, high density bovine articular chondrocyte (BAC) cultures, stimulated with transforming growth factor-beta-1, elaborated a high molecular weight anionic glycoconjugate, kDa 540, which does not contain glycosaminoglycan chains (Chan and Anastassiades, 1996). The effect of exogenously added transforming growth factor-beta-1 on the elaboration of the high molecular weight glycoconjugate and of proteoglycans was studied during dedifferentiation of the chondrocytes, utilizing a serial subculture technique under anchorage-dependent conditions, up to four subcultures. The high molecular weight glycoconjugate was detected in the media of all growth-factor-stimulated chondrocyte subcultures, as well as stimulated primary cultures, but not in unstimulated primary cultures or subcultures. By contrast, a large proteoglycan, was only secreted by primary cultures and first subcultures, whether treated with transforming growth factor-beta-1 or untreated. This proteoglycan contained mostly chondroitin sulfate chains, whose hydrodynamic size was increased by the addition of transforming growth factor-beta-1. Further, the pattern of the proteoglycans appearing in the media of subcultures 2-4 was influenced by the addition of transforming growth factor-beta-1, so that while these control subcultures elaborated both the large and small chondroitin sulfate proteoglycans, the equivalent stimulated subcultures elaborated only intermediate sized chondroitin sulfate proteoglycan(s). These results suggest that while dedifferentiation of articular chondrocytes, achieved by subculturing, strongly modulates the effect of exogenously added transforming growth factor-beta-1 on the type of proteoglycan elaborated, the process of dedifferentiation does not influence the transforming-growth-factor-beta-dependent synthesis of the high molecular weight anionic glycoconjugate.

Animals↗
PubMed1988

Glycoconjugates secreted by bovine tracheal serous cells in culture.

Glycoconjugates secreted by bovine tracheal gland serous cells in culture were characterized after incorporation of radioactive precursor [1-14C]glucosamine and stimulation with isoproterenol. Under dissociative conditions, glycoconjugates eluted in both the void and included volumes on Sepharose Cl-4B. Fractionated by anion-exchange chromatography, the high-molecular-weight (Sepharose Cl-4B; V0) glycoconjugates gave two acidic fractions eluting at 0.5 and 2.0 M NaCl; low-molecular-weight glycoconjugates of the included volumes gave a neutral fraction and two acidic fractions eluting at 0.5 and 2.0 M NaCl. Based on chemical analysis and specific enzymatic digestions, the material eluting in the void volume was shown to contain hyaluronic acid and chondroitin sulfate proteoglycan. In addition, the presence of small amounts of galactose, fucose, sialic acid, glucosamine, and galactosamine suggest the presence of O-glycosidically linked glycoproteins in the void volume. The identification of galactosaminitol in beta-eliminated oligosaccharides from this material confirms this notion. The material eluting in the included volume was shown to contain N-linked glycoproteins with glycans of complex type in the neutral fraction and chondroitin sulfate proteoglycans in the two acidic fractions. Significant N-sulfation of amino sugars was detected in the 0.5 M acidic fraction, indicating the presence of heparan sulfate. Hyaluronic acid and chondroitin sulfate proteoglycan have recently been identified in tracheal secretions; our results suggest that these components originate at least in part from tracheal gland serous cells.

Animals↗
PubMed1991

Surface glycoconjugates of cynomolgus monkey trabecular cells.

Non-ionic detergent-soluble and detergent-resistant cynomolgus monkey trabecular cell surface glycoconjugates have been identified using three radiolabeling procedures and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The cell surface glycoconjugates were radiolabeled with tritiated sodium borohydride after treatment with: (1) neuraminidase/galactose oxidase; (2) galactose oxidase; or (3) sodium metaperiodate. The non-ionic detergent soluble components were removed by treatment of the monolayer cell culture with 1% Triton X-100 in hypotonic buffer. The radiolabeled trabecular cell surface glycoconjugates in the Triton X-100 soluble and insoluble fractions were resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions and visualized by fluorography. Treatment of the monkey trabecular cells with neuraminidase/galactose oxidase/tritiated sodium borohydride resulted in the radiolabeling of five components ranging in apparent molecular weight from 128,000 to 39,000 in the Triton X-100 soluble fractions, while 12 radiolabeled glycoconjugates with apparent molecular weights ranging from 240,000 to 26,000 were resolved in the Triton X-100 resistant fraction.

Animals↗
PubMed1991

Cell-specific alterations in glycoconjugates in the development of squamous metaplasia induced by benzo[a]pyrene in hamster tracheal explants.

Squamous metaplasia of tracheal mucosa, putative preneoplastic lesions, involves replacement of normal mucociliary epithelium with epidermoid lesions. Alterations in cell differentiation and neoplasia accompany changes in glycoconjugates at the plasma membrane. Lectins which bind to specific cell surface glycoconjugates are used to elucidate such alterations. We have used peanut agglutinin (PNA) and concanavalin A (Con A) as specific molecular probes to elucidate cell specific alterations in the development and progression of squamous metaplasia in the hamster tracheal explants induced by benzo[a]pyrene (BP), a component of cigarette smoke. The tracheal explants were cultured in serum-free chemically defined medium and treated with BP (7.5 micrograms/ml) for up to 15 days. At this time, 80-90% of the carcinogen treated explants exhibited epidermoid lesions at various stages of development. The untreated control explants maintained normal pseudostratified epithelium. In these explants, PNA and Con A exhibited moderate reaction in the cytoplasm of luminal mucociliary cells; the basal cells showed no reaction. In early metaplastic lesions PNA and Con A stained only the cytoplasm of luminal cells; the metaplastic cells along the basal lamina were negative. In well-developed lesions, in which the luminal mucociliary layer was still intact overlying the lesions, the metaplastic epithelium remained unreactive with the lectins. In highly advanced lesions exhibiting cornification, and in which the mucociliary layer was sloughed, the metaplastic lesions showed strong reaction with both the lectins. The reaction was limited mainly to the plasma membrane of the metaplastic cells. These results show that induction and progression of the BP induced lesions accompany dynamic cell specific alterations in glycoconjugates. The epidermoid lesions acquire glycoconjugates rich in beta-D-galactose and D-mannose. These results are also consistent with the basal cell origin of the metaplastic lesions.

Animals↗
PubMed1996

Identification of basal lamina acidic glycoconjugates, particularly heparan sulphate proteoglycans, using a poly-L-lysine-gold probe in induced oral carcinomas.

Acidic glycoconjugates represent the major non-fibrous macromolecular components that form the extracellular and cell-associated matrices of all animal tissues. The constituent molecules are principally structural glycoproteins and proteoglycans. While their protein component is determined by gene pools, it is the polyanionic (acidic) nature of the polysaccharides, determined by their degrees of carboxylation and sulphation, which confers both functional and diagnostic status on these molecules. Sulphated glycoconjugates in the basal laminae have been reported to play a role in tumour invasion and metastasis. In this study, we used cationic colloidal gold together with transmission electron microscopic methods to compare the expression of acidic glyconconjugates in the basal lamina of both normal rat tongue mucosa and experimentally induced oral carcinomas. Results indicated that heparan sulphate rich glycoconjugates were predominant and were mostly confined to the lamina lucida of the basal lamina in normal oral mucosa. Conversely, observation of basal laminae associated with induced carcinomas showed less intense and more widely dispersed gold labelling for heparan sulphate. The observed differences in gold labelling may reflect modified metabolism of sulphated glycoconjugates or result from the action of degradative enzymes in the induced tumours.

4-Nitroquinoline-1-oxide↗
PubMed2006

Sugar-dependent aggregation of glycoconjugated chlorins and its effect on photocytotoxicity in HeLa cells.

In order to explore the influence of the sugar moieties of glycoconjugated chlorins on the photocytotoxicity, we studied the photochemical properties of four glycoconjugated chlorins in aqueous media such as cytoplasm and the concentration dependence of photocytotoxicity in HeLa cells. In phosphate-buffered saline, the fluorescence intensities of 5,10,15,20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin (m-1a) and 5,10,15,20-tetrakis[3-(beta-D-galactopyranosyloxy)phenyl]chlorin (m-1b), i.e., chlorins having hexose groups, were about 2-fold greater than those of 5,10,15,20-tetrakis[3-(beta-d-xylopyranosyloxy)phenyl]chlorin (m-1c) and 5,10,15,20-tetrakis[3-(beta-d-arabinopyranosyloxy)phenyl]chlorin (m-1d), i.e., chlorins having pentose groups, owing to a sugar-dependent difference of aggregation behavior. While no cytotoxicity was found in the dark, the highest photocytotoxicity was shown by m-1a (82% inhibition) in HeLa cells. This was higher than those of m-1b, m-1c, m-1d and tetraphenylporphyrin tetrasulfonic acid. The glycoconjugated chlorins except for m-1b appeared to be distributed diffusely throughout the cytoplasm. Among the four photosensitizers, m-1a showed the highest intensity in confocal fluorescence images, in agreement with the in vitro photocytotoxicity results. For m-1c, no photocytotoxicity was found at drug concentrations from 0.2 to 0.04 microM. Hence, sugar-dependent aggregation is not the major reason for the unexpected lack of efficacy of m-1c, which is uptaken efficiently by HeLa cells. For the glycoconjugated chlorins, these results suggest the biological aspects of sugar moiety play much crucial role rather than chemical aspects.

Biological Transport↗
PubMed2000

Heterogeneous distribution of plasma membrane glycoconjugates in pancreatic acinar cells.

Flow-cytometric studies of lectin binding to individual acinar cells have been carried out in order to analyse the distribution of membrane glycoconjugates in cells from different areas of the pancreas: duodenal lobule (head) and splenic lobule (body and tail). The following fluoresceinated lectins were used: wheat germ agglutinin (WGA), Tetragonolobus purpureus agglutinin (TP) and concanavalin A (Con A), which specifically bind to N-acetyl D-glucosamine and sialic acid, L-fucose and D-mannose, respectively. In both pancreatic areas, two cell populations (R1 and R2) were identified according to the forward scatter (size). On the basis of their glycoconjugate pattern, R1 cells displayed higher density of WGA and TP receptors than R2 cells throughout the pancreas. Although no difference in size was found between the cells from duodenal and splenic lobules, N-acetyl D-glucosamine and/or sialic acid and L-fucose residues were more abundant in plasma membrane cell glycoconjugates from the duodenal lobule. The results provide evidence for biochemical heterogeneity among individual pancreatic cells according to the distribution of plasma membrane glycoconjugates.

Animals↗
PubMed1990

Boundaries during normal and abnormal brain development: in vivo and in vitro studies of glia and glycoconjugates.

This paper focuses on transient boundaries of glia and glycoconjugates during development of the mouse central nervous system (CNS). Lectin-bound glycoconjugates, glial fibrillary acidic protein, and the J1/tenascin glycoprotein are distributed coextensively within boundaries around developing substructural arrangements (e.g., developing nuclei, and at a finer level, somatosensory cortical "barrels" related to individual facial vibrissae) throughout the CNS during pattern formation events. Electron microscopy has shown that the J1/tenascin glycoprotein, for example, is present in immature astrocytes, on glial and neuronal plasma membranes, and within the pericellular space that could be extracellular matrix (ECM). The findings presented on the expression of this well-characterized ECM molecule suggest that previously described glial and glycoconjugate boundaries reported by our group are in part composed of specific recognition molecules. The J1/tenascin glycoprotein, a chondroitin sulfate-containing antigen termed the 473 proteoglycan, and the adhesion molecule on glia are expressed within discrete boundary regions and associated axonal pathways. There, they may sculpture fine aspects of functional cytoarchitectonic arrangements and help guide axons to specific targets. The expression and developmental regulation of glycoproteins such as J1/tenascin may thus be integral events during pattern formation and synaptogenesis in the CNS. The presence of abnormal glial arrangements and glycoconjugate boundaries in the cortices of the genetic mutant mouse reeler, and findings on plasticity of boundaries following various perturbations, suggest that boundary expression is controlled by both genetic and epigenetic factors. Some future directions for studying developmental boundaries, including use of cultured explants for in vitro "bioassays," are also discussed.

Aging↗
PubMed1988

Lectin and ultrastructural cytochemistry of glycoconjugates in the cecal epithelium of the chicken.

In the cecal epithelium of the chicken, glycoconjugates were studied by light microscopy with lectin-peroxidase and correlated procedures, and by electron microscopy with high iron diamine-thiocarbohydrazide-silver proteinate (HID-TCH-SP) and periodic acid (PA)-TCH-SP methods. Mucous granules of goblet cells and striated border of columnar cells at the basal cecum contained acidic and neutral glycoconjugates with sulfate ester, vicinal diol groupings and alpha-D-mannose, alpha-D-glucose, beta-D-galactose, N-acetyl-D-glucosamine, and sialic acid-galactose dimers. In addition, terminal galactose-(1-3)N-acetylgalactosamine disaccharides were detected. In the apical cecum, similar glycoconjugates involved in the mucous granules of goblet cells and the striated border of columnar cells were found to be smaller in amount. Terminal galactose-(1-3)N-acetylgalactosamine disaccharides together with glycogen particles were also visualized in columnar cells of the basal and apical cecum. The histophysiological significance of glycoconjugates involved in the chicken cecal epithelium was discussed.

Animals↗
PubMed2004

Solid phase assays in glycoconjugate research: applications to the analysis of proteoglycans, glycosaminoglycans and metalloproteinases.

Glycoconjugates are a class of macromolecules consisting of different constituents, one of which is sugar moieties. Glycoconjugates comprise the majority of tissue constituents, both intracellular and extracellular. Extracellular glycoconjugates (glycoproteins and proteoglycans) participate in a wide variety of interactions, through which they maintain tissue integrity. Therefore, their analysis or the study of their possible interactions would give evidence for the state of tissues. Since the amounts of some of the extracellular glycoconjugates are usually low or the amounts of tissue to be examined come from biopsies, specific analytical systems are developed for their study, the most familiar being solid phase assays, which have the advantages of analysis of multiple samples on the same time, cheap instrumentation and high specificity.

Enzyme-Linked Immunosorbent Assay↗
PubMed2002

Glycoconjugate histochemistry of bovine Brunner glands.

The principal aims of this study have been to elucidate the nature of glycoconjugates produced by the two distinct parts of bovine Brunner glands, peripheral and central areas of lobules, and to investigate the presence of sialyl acid residues. Bovine duodenal tissues, embedded in paraffin wax, were investigated by means of both conventional histochemical methods (PAS, AB, HID) and biotinylated lectins (Con A, DBA, SBA, GS-I-B4, PNA, sWGA, GS-II, UEA-I, LPA, LFA). Conventional histochemical methods allowed us to accurately define two different areas: a central and a peripheral area. The central area, composed of secretory tubular tracts and the excretory duct, contained neutral glycoconjugates. The peripheral area was formed by both terminal alveolar and tubular secretory tracts and contained both neutral and acidic glycoconjugates, the latter partly carboxylated and partly sulfated. Lectin histochemistry confirmed differences highlighted by conventional histochemical methods and allowed us to characterise glycoprotein profiles of the preterminal and terminal tracts. The preterminal tracts and the excretory duct contained glycoconjugates with terminal D-Gal beta(1-3)GalNAc, alpha-D-Gal, alpha/beta-D-GalNAc, alpha/beta-D-GlcNAc, and internal beta(1-4) D-GlcNAc and alpha-Man residues. The terminal tracts were characterised by terminal alpha-L fucose, beta-D-GalNac, alpha/betaD-GlcNAc, alpha-D-Gal, alpha-D-GalNAc, and sialic acid residues. Internal beta(1-4) D-GlcNAc and alpha-Man residues were also identified. Finally, secretion of bovine Brunner glands is characterised by both O-linked and N-linked glycoproteins: cells located in the preterminal tracts and in the excretory duct produce mainly O-linked glycoproteins while cells located in the terminal tracts produce N-linked glycoproteins.

Animals↗
PubMedDate not supplied

Evaluation of different alpha-Galactosyl glycoconjugates for use in xenotransplantation.

Porcine organs are rapidly rejected after transplantation into primate recipients due to the presence of preexisting immunoglobulins that bind to terminal galactose alpha1,3 galactose residues (alpha-galactosyl) present on porcine glycoproteins and glycolipids. Currently available immunosuppressive reagents have been largely ineffective at controlling the synthesis of these anti-Gal antibodies. Nonantigenic hapten polymers have been shown to be effective materials for blocking humoral immune responses in various model systems. We have developed a series of alpha-galactosyl glycoconjugate polymers and tested their ability to block anti-Gal antibody binding in vitro and in vivo. A galactose alpha1,3 galactose beta 1,4 GlcNAc trisaccharide free acid (TRFA) with a hexanoic acid spacer, containing five methylene groups and a carboxylic acid, was produced and coupled to a variety of polymeric backbones including dextran, branched poly(ethylene glycol) (PEG), and poly-L-lysine. The ability of monomeric TRFA and the alpha-galactosyl conjugates to block anti-Gal IgG and IgM binding was determined using a competition ELISA assay on defined HSA-Gal glycoconjugates and porcine microvascular endothelial cell substrates. We show that branched PEG carriers, with a TRFA sugar attached to each branch, exhibit enhanced antibody blocking ability compared to TRFA, but at higher target antigen densities these simple PEG conjugates are no more effective then an equivalent amount of TRFA in blocking anti-Gal IgM antibody interactions. In contrast, polymers of the branched PEG conjugates and linear conjugates made using dextran and poly-L-lysine were 2000 to 70000-fold more effective inhibitors of anti-Gal antibodies. In a study using nonhuman primates, a single dose infusion of polymeric PEG or dextran glycoconjugates dramatically reduced the level of circulating anti-Gal antibodies in cynomologus monkeys for at least 72 h. Glycoconjugates similar to these might be useful both to block anti-Gal interactions in vivo and to specifically control the induced anti-Gal immune response.

Animals↗
PubMed2002

Expression pattern of glycoconjugates in rat retina as analysed by lectin histochemistry.

The present study sought to characterize the expression and distribution of complex glycoconjugates in the rat retina by lectin histochemistry, using a panel of 21 different lectins with different carbohydrate specificities. Paraffin sections of Carnoy-fixed Sprague-Dawley rat eyes were stained with various biotinylated lectins, followed by the streptavidin-peroxidase and glucose oxidase-diaminobenzidine-nickel staining procedures. The results showed that the retinal pigment epithelium was stained intensely with LCA, Jacalin, WFA, S-WGA, PWA, DSA, UEA-I, LTA and PHA-E, suggesting that this epithelium contained glycoconjugates with alpha-Man, alpha-Glc, alpha-Gal/GalNAc, beta-GalNAc, alpha-Fuc, NeuAc and other oligosaccharide residues. The outer and inner segments of the photoreceptor layer showed different lectin binding affinities. The outer segments reacted with S-WGA and GS-II, whereas the inner segments reacted with UEA-II, UEA-I, LTA and MAA, suggesting that the inner segments contained glycoconjugates rich in alpha-Fuc and NeuAc(alpha2,3)Gal residues. PNA labelled specifically the cones and could be used as a specific marker for these photoreceptors. RCA-I, WFA, S-WGA, DSA, MAA and PHA-E reacted with both the outer and inner plexiform layers. On the other hand, UEA-I and LTA specifically labelled the outer plexiform layer, while PNA labelled the inner plexiform layer. The retinal microglial cells were labelled specifically by GS-I-B4 and SNA. Interestingly, we also observed that WFA bound specifically to Müller cells and could be used as a novel marker for this retinal glial cell. The capillaries and larger vessels in the retina and choriocapillaris reacted intensely with GS-I-B4, RCA-I, S-WGA, PWA, DSA and PHA-E. No significant differences in lectin binding were observed in the microvessels at these two sites. In summary, the present study demonstrated the expression patterns of glycoconjugates in the rat retina and that certain lectins could be used as histochemical markers for specific structural and cellular components of the rat retina.

Animals↗
PubMed1995

The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes.

Treatment of rat hepatocytes with 0.5 mM concentrations of uridine and cytidine results in increased cellular concentrations of UTP, UDP-sugars and CTP, whereas that of CMP-N-acetylneuraminate remained unchanged [Pels Rijcken, Overdijk, Van den Eijnden and Ferwerda (1993) Biochem. J. 293, 207-213]. The incorporation of radioactivity from 3H-labelled sugars into the cell-associated and secreted glycoconjugate fraction was influenced by these altered cellular concentrations of the nucleotides. For [3H]glucosamine, pretreatment with uridine resulted in a reduction of the glycosylation in both fractions. Increases in the secreted fractions were observed for fucose with both uridine and cytidine and for N-acetylglucosamine with uridine only. With [3H]N-acetylglucosamine, similar specific radioactivities for UDP-N-acetylhexosamine and CMP-N-acetylneuraminate were found, regardless of the pretreatment conditions. With [3H]N-acetylmannosamine, the specific radioactivity of CMP-N-acetylneuraminate showed an almost 2-fold increase on pretreatment. The latter increase did not result in an increased incorporation of radioactivity into the glycoconjugates. It was estimated that, in untreated cells, the ratio of radioactivity incorporated from [3H]glucosamine into glycoconjugate-bound N-acetylhexosamine and N-acetylneuraminate amounted to 2:3. In pretreated cells this ratio changed to approx. 2:1. Overall, the data show that pretreatment resulted in an increased incorporation of N-acetylhexosamine into cell-associated and secreted glycoconjugates, accompanied by a reduction in sialylation. It was concluded that an increased availability of UDP-N-acetylhexosamine caused the increased incorporation of N-acetylhexosamine. The elevated cytosolic level of UDP-N-acetylhexosamine (and of compounds like CMP) is suggested to impair the transport of CMP-acetylneuraminate to the Golgi, resulting in reduced sialylation. This study demonstrates that protein glycosylation can be regulated at the level of the availability of the various nucleotide-sugars in the Golgi lumen.

Acetylglucosamine↗
PubMed2001

Glycoconjugate abnormalities in patients with congenital dyserythropoietic anaemia type I, II and III.

Congenital dyserythropoietic anaemia type II (CDA II) is well known for glycosylation abnormalities affecting erythrocyte membrane glycoconjugates that encompass hypoglycosylation of band 3 glycoprotein and accumulation of glycosphingolipids: lactotriaosylceramides, neolactotriaosylceramide and polyglycosylceramides. These abnormalities were not observed in erythrocytes from patients with CDA of either type I or III. Recently, however, we have described a CDA type I patient in Poland with identical, though less pronounced, glycoconjugate abnormalities to those observed in patients with CDA type II. The abnormalities included partial unglycosylation of O-linked glycosylation sites in glycophorin A. These abnormalities are now reported in three Bedouin patients from Israel with CDA type I. In addition, the erythrocyte membranes of these patients exhibited highly increased globotetraosylceramide content. Glycoconjugate abnormalities were also present in erythrocyte membranes from three patients from Northern Sweden with CDA type III but they almost exclusively affected glycosphingolipids. In erythrocytes of all patients examined including one with CDA type II, polyglycosylceramides were significantly hypoglycosylated although, on a molar basis, their contents in erythrocyte membranes were increased. Thus, glycoconjugate abnormalities of varying intensity occur in erythrocyte membranes from all patients with CDA that were investigated.

Anemia, Dyserythropoietic, Congenital↗
PubMed1997

Synthesis of glycoconjugates by human diseased veins: modulation by procyanidolic oligomers.

Venous diseases become steadily more common and severe with age, and are often accompanied by venous lymphatic oedema. We have investigated the role of glycoconjugates in this disorder and the action of procyanidols used to treat these diseases. Explants of vein wall from patients with or without venous lymphatic edema were cultured for 24 hours and the incorporation of radioactive glucosamine into total glycoconjugates and into hyaluronan was measured. The explants from patients with oedema incorporated more glucosamine than those without oedema (+42% expressed as c.p.m./mg dry weight into total glycosaminoglycans and +12% expressed as c.p.m./mg dry weight into hyaluronan). The explants from oedematous patients secreted less glycoconjugates into the culture medium than those from non-oedematous veins (-63% of total incorporated radioactivity into hyaluronan and -66% into hyaluronidase-resistant glycoconjugates). Explants placed in medium containing procyanidols (1 mg/ml, 2.8 mM) incorporated less glucosamine (-19%) and secreted more into the medium (+119%). Glycoprotein and sulphated glycosaminoglycan synthesis were mainly affected which may well explain the beneficial effect of procyanidols on vein disorders.

Adult↗