Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycosylation of the G-protein was analyzed in vesicular stomatitis virus-infected baby hamster kidney cells incubated in the absence of glucose. The results indicate that the G-protein in glucose-starved cells is initially glycosylated from a lipid donor with a glucosylated oligosaccharide which is resistant to endo-beta-N-acetylglucosaminidase H and partially susceptible to alpha-mannosidase. With longer times, the protein-bound carbohydrate chain becomes much more sensitive to alpha-mannosidase while remaining endo-beta-N-acetylglucosaminidase H-resistant. Purified virions from glucose-starved baby hamster kidney cells, labeled with [35S]methionine and isolated on a sucrose gradient, contain altered forms of the G-protein, whereas the other viral proteins remain unchanged. These altered forms could also be radiolabeled with [3H]mannose, and upon analysis of labeled glycopeptides by chromatography on concanavalin A-Sepharose and Bio-Gel P-6, it was apparent that modification of the oligosaccharide portion of the G-protein occurs in baby hamster kidney cells, leading to aberrant mature carbohydrate chains.
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PMID:Altered G-protein glycosylation in vesicular stomatitis virus-infected glucose-deprived baby hamster kidney cells. 628 41

Membrane bound polysomes were prepared from HeLa cells infected with vesicular stomatitis virus (VSV), after pulse labeling with [3H]mannose for various times from 15 to 90 min. Oligosaccharides on nascent chains were released from peptides by treatment with endoglycosidase H and sized by high resolution Biogel P4 chromatography. Processing on some nascent chains proceeded to the removal of all three types of alpha-linked glucose and one alpha-1,2-mannose from the Glc3Man9GlcNAc precursor showing that the enzymes responsible were not only active on nascent chains but were present in the rough endoplasmic reticulum (RER). Incubation of cells for various times in cycloheximide, where chain elongation had ceased, made no difference to the profile of oligosaccharides on the nascent chains, and trimming proceeded no further than Man8GlcNAc2Asn . Carbonyl cyanide m-chlorophenylhydrazone (CCCP), an energy inhibitor reportedly able to block the transfer of glycoproteins from the RER, increases the amount of Man8-oligosaccharides on the nascent chains and also the amount of Glc3Man9GlcNAc precursor. On completed G protein in the RER fraction from which membrane bound polysomes were prepared, processing occurred to Man6 - but not to Man5GlcNAc sized oligosaccharides in the CCCP-treated cells. By contrast, processing to Man5GlcNAc oligosaccharides was observed in unfractionated control cells.
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PMID:Co-translational excision of alpha-glucose and alpha-mannose in nascent vesicular stomatitis virus G protein. 632 29

We have studied the effects of inhibiting the initial steps in processing of asparagine-linked oligosaccharides on the formation of vesicular stomatitis virus (VSV). Our data show that conditions which prevent the removal of glucose can block the growth of this virus. Our conclusion that inhibition of VSV synthesis is due specifically to an effect on the ability of the virus glycoprotein, G, to mature to a correct functional conformation is based on the following observations: (i) two drugs, deoxynojirimycin and castanospermine , both of which selectively inhibit the processing glucosidases, affected virus growth; (ii) only one of the two strains (San Juan and Orsay ) of VSV tested was affected and that strain, VSV(San Juan), is known to have a G protein highly sensitive to alterations in oligosaccharide structure; (iii) the effect was to make the formation of VSV(San Juan) temperature-sensitive, a result previously observed with alterations in the oligosaccharides on G protein; (iv) a cell variant missing glucosidase II activity also became temperature-sensitive in its ability to produce VSV(San Juan) but not VSV( Orsay ). Although inhibition of glucosidase activity by 1- deoxynojirimycin caused a 10-fold drop in virion formation, transport of G protein to the plasma membrane was not altered. The growth of VSV(San Juan) at 40 degrees C was not affected when subsequent steps in the processing pathway were blocked. These data indicate that by the time the glucose residues are removed G has attained a stable conformation.
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PMID:The formation of vesicular stomatitis virus (San Juan strain) becomes temperature-sensitive when glucose residues are retained on the oligosaccharides of the glycoprotein. 633 65

The features of 41 proven or suspected cases of pancreatic glucagonoma and one possible case of renal glucagonoma have been reviewed. Glucagonoma is one form of islet cell neoplasm and involves pancreatic alpha cells. It may occur more frequently in women and is more likely to be malignant than insulinoma. Patients may present with glucose intolerance, an erythematous, eczematous dermatitis, glossitis, stomatitis, vaginitis and unexplained weight loss. Anemia, hypoproteinemia, hypoaminoacidemia and hypolipidemia may also be present. Malignant glucagonoma metastasizes frequently to liver. An evaluation for possible glucagonoma may be considered in a patient with the characteristic eczematous dermatitis, glossitis or stomatitis and glucose intolerance, an unusual or atypical history of diabetes mellitus, or hepatomegaly with other characteristics of glucagonoma. Initial evaluation may include measurement of fasting plasma glucagon concentration, and an oral glucose tolerance test with measurements of plasma glucose and glucagon levels. Extreme fasting hyperglucagonemia, and a paradoxical rise in plasma glucagon concentrations after glucose ingestion should strongly suggest the presence of glucagonoma. Radiographic demonstration of pancreatic glucagonoma is best carried out by celiac arteriography. Surgical excision of the tumor is the treatment of choice. Nonresectable lesions may respond to chemotherapy with streptozotocin. Treatment for the various dermatologic or metabolic complications of glucagonoma which include glucose intolerance, hypoproteinemia, hypocholesterolemia and anemia may not be satisfactory. Glucose intolerance is usually mild and may be adequately treated with dietary or insulin therapy. Rarely, glucagonoma with massive destruction of the pancreas or other factors may induce severe glucose intolerance. In contrast, the anemia, skin rash, and hypoproteinemia do not respond to conservative therapies tested thus far. Glucagonoma is a model for studying the importance of glucagon in causing the hyperglycemia of diabetes mellitus. Study of patients with glucagonoma does suggest that glucagon has some role in the etiology of hyperglycemia in diabetic states; however, as in studies on diabetes, investigations on glucagonoma do not demonstrate that glucagon has a primary role in producing severe glucose intolerance.
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PMID:Clinical and metabolic aspects of glucagonoma. 698 81

Out of fifteen carriers of X-linked chronic granulomatous disease five had discoid lupus erythematosus-like skin lesions together with recurrent aphthous-like stomatitis, another five had only recurrent aphthous-like stomatitis, and the remainder were symptom-free. In individual carriers monocytes and neutrophils were equally reduced in their capacity for superoxide production, [1-14C]glucose oxidation and antibody-dependent cytotoxicity; but within he group of carriers a broad spectrum of depression was found. The degree of depression was closely related to the manifestations of clinical disease. It is suggested that the defective oxygen-dependent metabolism might play an aetiological role in the development of inflammatory diseases in carriers of chronic granulomatous disease. Two out of 10 unselected females with discoid lupus erythematosus were shown to be carriers of X-linked chronic granulomatous disease. Screening for this carrier state might therefore be of importance in these patients.
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PMID:Relation of monocyte and neutrophil oxidative metabolism to skin and oral lesions in carriers of chronic granulomatous disease. 727 85

Using a pulse-chase approach combined with immunoprecipitation, we showed that newly synthesized influenza virus hemagglutinin (HA) and vesicular stomatitis virus G protein associate transiently during their folding with calnexin, a membrane-bound endoplasmic reticulum (ER) chaperone. Inhibitors of N-linked glycosylation (tunicamycin) and glucosidases I and II (castanospermine and 1-deoxynojirimycin) prevented the association, whereas inhibitors of ER alpha-mannosidases did not. Our results indicated that binding of these viral glycoproteins to calnexin correlated closely with the composition of their N-linked oligosaccharide side chains. Proteins with monoglucosylated oligosaccharides were the most likely binding species. On the basis of our data and existing information concerning the role of monoglucosylated oligosaccharides on glycoproteins, we propose that the ER contains a unique folding and quality control machinery in which calnexin acts as a chaperone that binds proteins with partially glucose-trimmed carbohydrate side chains. In this model glucosidases I and II serve as signal modifiers and UDP-glucose:glycoprotein glucosyltransferase, as a folding sensor.
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PMID:Role of N-linked oligosaccharide recognition, glucose trimming, and calnexin in glycoprotein folding and quality control. 830 66

The Na+-dependent glucose transporter (SGLT1) mediates absorption of luminal glucose by the intestine. However, available intestinal cell lines that recapitulate a monolayer phenotype only express SGLT1 at low levels. Thus, to facilitate studies of the biology of SGLT1 function in epithelial monolayers, we engineered an epitope-tagged construct containing the YTDIEMNRLGK sequence (from the vesicular stomatitis virus G protein). The tag was placed at the carboxyl terminus since this is the least conserved portion of SGLT1. Transiently transfected COS-1 cells demonstrated surface expression of the immunoreactive protein and enhanced Na+-dependent glucose uptake that was phloridzin-sensitive (a specific competitive inhibitor of SGLT1). However, subsequent detailed analyses of epitope-tagged SGLT1 using stably transfected clones derived from the Caco-2 human intestinal epithelial cell line revealed substantial effects of the epitope on critical functions of SGLT1. When compared with native SGLT1 transfectants, the apparent Km for sugar transport was increased 23-fold (313 microM to 7.37 mM for native versus epitope-tagged SGLT1). In contrast, the apparent KNa for epitope-tagged SGLT1 was similar to that for native SGLT1. Permeabilization studies indicated that the C-terminal epitope tag was intracellular and thus could not directly disrupt extracellular ligand-binding sites. Immunolocalization and functional assays designed to detect polarized surface expression indicated that epitope tagging resulted in loss of apical targeting and enrichment of basolateral expression. Functional isolation of the small apical pool of epitope-tagged SGLT1 (by selective inhibition of basolateral epitope-tagged SGLT1) revealed that, despite the documented kinetic alterations in sugar transport, epitope-tagged SGLT1 could promote absorptive Na+ currents. These data show that 1) the C terminus of SGLT1 is intracellular; 2) disruption of protein structure by addition of a C-terminal tag leads to selective modifications of SGLT1 function; 3) the kinetics of sugar transport can be altered independently of influences on the Na+-binding site of SGLT1; and 4) the weak basolateral targeting sequence present within the epitope tag is dominant over endogenous SGLT1 apical targeting information and can direct polytopic membrane protein localization. The data also caution that subtle effects of foreign sequences must be considered when epitope tagging polytopic membrane proteins.
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PMID:Carboxy-terminal vesicular stomatitis virus G protein-tagged intestinal Na+-dependent glucose cotransporter (SGLT1): maintenance of surface expression and global transport function with selective perturbation of transport kinetics and polarized expression. 863 15

The prevalence of denture stomatitis as well as the frequency of isolation of Candida species and their density on the palatal mucosa have been compared in 70 acrylic denture-wearers suffering from non-insulin-dependent diabetes mellitus (NIDDM) versus 58 acrylic denture-wearers with normal glucose metabolism. The adherence of C. albicans to palatal epithelial cells in vitro was also assessed in both groups. The patients with NIDDM had a significantly higher prevalence of denture stomatitis compared with the controls. The frequency of Candida colonization was increased in diabetics, but not significantly. According to the imprint culture technique, the density of Candida species was significantly higher in patients with NIDDM compared with the controls. The adherence of C. albicans to palatal epithelial cells from patients with NIDDM showed a significant increase compared with that observed in cells collected from the controls. This study supports the view that NIDDM predisposes to Candida-associated denture stomatitis.
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PMID:Non-insulin-dependent diabetes mellitus as a risk factor for denture stomatitis. 893 Aug 17

Studies designed to elucidate the mechanism of regulation of the GLUT1 isoform of the glucose transporter in response to a variety of cellular stresses are reviewed. Using ts mutants of vesicular stomatitis virus, it was shown that the viral L gene was responsible for the stimulation of glucose transport in infected cells. Immunofluorescence of GLUT1 demonstrated that the increase in glucose transport was the consequence of a translocation of the transporter from a reservoir in cytoplasmic vesicles to the plasma membrane. When cells were cycled between deficient and standard medium, the change in glucose transport rates was paralleled by a cycling of the transporter between the plasma membrane and the cytoplasmic vesicles. The redistribution of GLUT1 was not a consequence of a general redistribution of recycling plasma membrane proteins. Instead, the findings focus attention on the regulated exocytosis of specific membrane constituents in cells that, until recently, were not thought to exhibit this capacity.
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PMID:Control of glucose transport by GLUT1: regulated secretion in an unexpected environment. 915 74

Parental Chinese hamster ovary (CHO) cells were mutagenized and subjected first to a mannose suicide selection technique and second to a screen of individual colonies grown on polyester discs for reduced mannose incorporation into protein. The incorporation of radioactivity for the selection and the screen was conducted at 41.5 degrees C instead of the normal growth temperature of 34 degrees C in order to allow for the isolation of temperature-sensitive lesions. This selection/screening procedure resulted in the isolation of M15-4 cells, which had three- to five-fold lower incorporation of [2-3H]mannose into mannose 6-phosphate, mannose 1-phosphate, GDP-mannose, oligosaccharide-lipid, and glycoprotein at 41.5 degrees C. We detected no difference in the qualitative pattern of mannose-labeled lipid-linked oligosaccharides compared to parental cells. M15-4 cells synthesized dolichol. The defect of M15-4 cells was determined to be in hexokinase activity; crude cytosolic extracts were eight- to nine-fold lower in hexokinase activity in M15-4 cells compared to parental cells. As a result of this defect, incorporation of labeled mannose from the medium was significantly decreased. However, the level of GDP-mannose in M15-4 cells was 70% of normal. The phenotype of M15-4 was a lower specific activity of labeled GDP-mannose, not a substantial reduction in the level of GDP-mannose. Consistent with these results, no alterations in the glycosylation of a model glycoprotein, G protein of vesicular stomatitis virus, were observed. These cells grew slower than parental cells, especially in low-glucose medium.
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PMID:Chinese hamster ovary cells with reduced hexokinase activity maintain normal GDP-mannose levels. 1002 67


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