Infantile cystinosis in France: genetics, incidence, geographic distribution.
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A national distribution of 66 French patients, from 49 sibships, has been studied. Segregation analysis, using the maximum likelihood method, was found to agree with the theoretical values expected in recessive autosomal inheritance. The birthplaces of these patients show an unequal geographic distribution of cystinosis, the incidence being higher in Western France. Compared with the total number of live births during the period 1959 to 1972, the minimum incidence of the condition in the province of Brittany is 1 per 25 909, and the gene frequency 0.0062. In the rest of France, the minimum incidence is 1 per 326,440 and the gene frequency 0.0018. Application of Dahlberg's formula gives a similar result. The mean inbreeding coefficient is 530 X 10(-5), a figure 23 times higher than the mean coefficient of France. An indirect test of inbreeding, the distance between parental birthplaces, was studied, first using the French administrative boundaries, second by using kilometers. This distance was constantly smaller for the parents of patients than for the parents of controls. Analysis of two erythrocyte polymorphisms (ABO and Rh) showed a large excess of group A patients when compared with overall French data. These findings are difficult to interpret on genetic grounds. The genetic reasons for the unequal geographic distribution of cystinosis in France are discussed. (+info)
Acquisition of human blood group antigens by Schistosoma mansoni.
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Juvenile forms of Schistosoma mansoni (schistosomula) have been cultured in human blood of various specificities and tested for the presence of blood group substances on their surfaces. The tests employed were survival following transfer into rhesus monkeys immunized against human blood substances, mixed agglutination reactions, and immunofluorescence. A, B, H AND Lewisb+ antigens were expressed at the surface when the parasites were cultured in blood of appropriate specificities. Rhesus, M N S, AND Duffy antigens could not be detected on the parasite surface following culture. The evidence suggests that the expressed blood group antigens are of host origin and are acquired by the parasite during culture, probably in the form of glycolipids or megaloglycolipids. It is likely that these substances are also acquired by parasites in the bloodstream of man. They may serve to mask surface parasite antigens, and so enable schistosomes to evade parasite-specific humoral or cellular immune responses. (+info)
H (0) blood group determinant is present on soluble human L-selectin expressed in BHK-cells.
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In the present study we show that the H (0) blood group determinant Fuc alpha1-2Gal beta1-4GlcNAc beta1-R is present on N-linked glycans of soluble human L-selectin recombinantly expressed in baby hamster kidney (BHK) cells. The glycans were isolated using complementary HPLC techniques and characterized by a combination of exoglycosidase digestion and mass spectrometry. The linkage of the fucose residues was determined by incubation of the glycans with specific fucosidases. The H blood determinant Fuc alpha1-2Gal beta1-4GlcNAc beta1 was detected for bi-, 2,4 branched tri- and tetraantennary structures. To our knowledge, the proposed oligosaccharide structures represent a new glycosylation motif for recombinant glycoproteins expressed on BHK cells. (+info)
Poly-N-acetyllactosamine synthesis in branched N-glycans is controlled by complemental branch specificity of I-extension enzyme and beta1,4-galactosyltransferase I.
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Poly-N-acetyllactosamine is a unique carbohydrate that can carry various functional oligosaccharides, such as sialyl Lewis X. It has been shown that the amount of poly-N-acetyllactosamine is increased in N-glycans, when they contain Galbeta1-->4GlcNAcbeta1-->6(Galbeta1-->4GlcNAcbeta1 -->2)Manalpha1-->6 branched structure. To determine how this increased synthesis of poly-N-acetyllactosamines takes place, the branched acceptor was incubated with a mixture of i-extension enzyme (iGnT) and beta1, 4galactosyltransferase I (beta4Gal-TI). First, N-acetyllactosamine repeats were more readily added to the branched acceptor than the summation of poly-N-acetyllactosamines formed individually on each unbranched acceptor. Surprisingly, poly-N-acetyllactosamine was more efficiently formed on Galbeta1-->4GlcNAcbeta1-->2Manalpha-->R side chain than in Galbeta1-->4GlcNAcbeta1-->6Manalpha-->R, due to preferential action of iGnT on Galbeta1-->4GlcNAcbeta1-->2Manalpha-->R side chain. On the other hand, galactosylation was much more efficient on beta1,6-linked GlcNAc than beta1,2-linked GlcNAc, preferentially forming Galbeta1-->4GlcNAcbeta1-->6(GlcNAcbeta1-->2)Manalph a1-->6Manbeta -->R. Starting with this preformed acceptor, N-acetyllactosamine repeats were added almost equally to Galbeta1-->4GlcNAcbeta1-->6Manalpha-->R and Galbeta1-->4GlcNAcbeta1-->2Manalpha-->R side chains. Taken together, these results indicate that the complemental branch specificity of iGnT and beta4Gal-TI leads to efficient and equal addition of N-acetyllactosamine repeats on both side chains of GlcNAcbeta1-->6(GlcNAcbeta1-->2)Manalpha1-->6Manbet a-->R structure, which is consistent with the structures found in nature. The results also suggest that the addition of Galbeta1-->4GlcNAcbeta1-->6 side chain on Galbeta1-->4GlcNAcbeta1-->2Man-->R side chain converts the acceptor to one that is much more favorable for iGnT and beta4Gal-TI. (+info)
A predominantly hydrophobic recognition of H-antigenic sugars by winged bean acidic lectin: a thermodynamic study.
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The thermodynamics of binding of winged bean (Psophocarpus tetragonolobus) acidic agglutinin to the H-antigenic oligosaccharide (Fucalpha1-2Galbeta1-4GlcNAc-oMe) and its deoxy and methoxy congeners were determined by isothermal titration calorimetry. We report a relatively hydrophobically driven binding of winged bean acidic agglutinin to the congeners of the above sugar. This conclusion is arrived, from the binding parameters of the fucosyl congeners, the nature of the enthalpy-entropy compensation plots and the temperature dependence of binding enthalpies of some of the congeners. Thus, the binding site of winged bean acidic agglutinin must be quite extended to accommodate the trisaccharide, with non-polar loci that recognize the fucosyl moiety of the H-antigenic determinant. (+info)
Normal human serum contains natural antibodies reactive with autologous ABO blood group antigens.
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It is widely accepted that the serum of healthy individuals contains natural antibodies only against those blood group A or B antigens that are not expressed on the individual's red blood cells. The mechanisms involved in tolerance to autologous blood group antigens remain unclear. In the present study, we show that IgM and IgG antibodies reactive with autologous blood group antigens are present in the immunoglobulin fraction of normal human serum. Natural IgG anti-A antibodies purified by affinity chromatography from IgG of individuals of blood group A exhibited an affinity for A trisaccharide antigen in the micromolar range and agglutinated A red cells at sixfold higher concentrations than those required for agglutination with affinity-purified anti-A IgG of individuals of blood group B. Whereas autoantibodies reactive with self A and B antigens are readily detected in purified IgG and IgM fractions, their expression is restricted in whole serum as a result of complementary interactions between variable regions of antibodies. These observations suggest that tolerance to autologous ABO blood group antigens is dependent on peripheral control of antibody autoreactivity. (+info)
Purification and characterization of an anti-(A+B) specific lectin from the mushroom Hygrophorus hypothejus.
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A lectin (HHL) was isolated from the fruiting body of the mushroom Hygrophorus hypothejus by a combination of affinity chromatography on stromas of group B erythrocytes embedded in polyacrylamide gel, and DEAE-trisacryl and gel filtration chromatography. Its molecular mass, as determined by gel filtration, is estimated to be 68000 kDa and its structure is tetrameric with four identical subunits assembled with non-covalent bonds. HHL agglutinates specifically A and B blood group erythrocytes and in hemagglutination inhibition assays, exhibits sugar-binding specificity toward lactose, the anomeric alpha form being more effective than the beta form. (+info)
Alteration of sialyl Lewis epitope expression in pterygium.
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PURPOSE: Mucin-related antigens are abundantly expressed by the cells of the normal human conjunctiva. The pattern of these antigens in pterygium, and especially the role of Galbeta1-3GlcNAc alpha2,3-sialyltransferase (ST3Gal III), sialyltransferase necessary to build the sialyl-Le(a) (Lewis(a)) antigen, were studied. METHODS: Immunoperoxidase staining was performed on 28 pterygia using different monoclonal antibodies: anti-M1 (against the peptidic core of gastric mucins encoded by MUC 5AC gene), anti-Le(a)(7LE), anti-sialyl Le(a)(NS 19-9), and anti-Le(b)(2-25LE). A serologic Lewis determination was done in 18 patients. ST3Gal III sialyltransferase expression was also studied in 10 healthy conjunctiva and 10 pterygia by reverse transcriptase-polymerase chain reaction (RT-PCR). Glyceraldehyde-3-phosphate-dehydrogenase was used as an endogenous internal control. RESULTS: First, Le(a), sialyl Le(a), and Le(b) immunoreactivities either decreased or were no longer detectable in pterygium goblet cells as opposed to normal conjunctiva. Second, unlike in pterygium, the Lewis immunoreactivity, which is mainly located in the surface epithelial cells in the normal conjunctiva, was occasionally restricted to the epithelial cells of the deep layers. However, M1 mucins did show an identical pattern expression in a normal conjunctiva and pterygium. ST3Gal III expression was significantly lower in pterygium (0.20+/-0.02 AU [arbitrary units]) than in normal conjunctiva (0.95+/-0.12 AU). CONCLUSIONS: ST3Gal III gene is less expressed in pterygium than in normal conjunctiva. This observation could explain the decrease of sialyl Le(a) expression observed in pterygium by immunohistology. (+info)