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Biomedical subjects

B E Samuelsson

Publications and source records attributed to B E Samuelsson.

At least 55 records · Page 3Linked to original sources

Structural characterization of non-acid glycosphingolipids in kidneys of single blood group O and A pigs.

Total non-acid glycosphingolipids were isolated from the kidneys of single pigs serologically typed on their red blood cells as blood groups O and A. Glycolipid species were purified by HPLC and structurally characterized by thin-layer chromatography, mass spectrometry, proton NMR spectroscopy, degradation analysis, and reactivity with various monoclonal antibodies, Gal alpha 1-4Gal-specific E. coli bacteria, and lectins. Glucosyl-, globotriaosyl-, and globotetraosylceramides were the predominant molecular species with lactosyl- and globopentaosylceramides (IV3GalGb4Cer) as abundant constituents too. Small amounts of galactosyl- and digalactosylceramides were also present. In the blood group O pig kidneys, blood group H antigens based on four different core saccharides (types 1, 2, 4, and lactosyl core) were identified and the major blood group structure was V2FucIV3Gal-Gb4Cer. In the kidneys from the blood group A pig the corresponding blood group A antigens were found and in addition, a type 3 chain blood group A antigen was indicated by mass spectrometry and by its reactivity with a monoclonal antibody. Trace amounts of the type 2 chain-based X and Y antigens were found while blood group B antigens and the type 1 chain based Lewis antigens could not be detected. The ceramide part of the glycolipids was mainly composed of dihydroxy 18:0 long chain bases and non-hydroxy 16:0-24:0 fatty cids.

ABO Blood-Group System↗

ABO-incompatible kidney transplantation (A2 to O). Qualitative and semiquantitative studies of the humoral immune response against different blood group A antigens.

The humoral immune response against blood group A antigens with different core saccharide structures has been investigated in four blood group O recipients transplanted with kidneys from two blood group A2 donors. Radioimmunoassay and thin-layer chromatogram binding assay studies showed that different individuals responded differently to the same antigenic stimulus. Antibodies were produced in the recipient that bound to the terminal trisaccharide of the blood group A antigens. In some cases antibodies that bound to a larger antigen epitope, including the fourth and fifth sugar in the polysaccharide core chain, also occurred. Immunoglobulin class-specific, as well as subclass specific, responses were seen. The antibody response in the blood group O recipients receiving an A2 graft seem to be dependent on the antigenic expression in the transplanted kidney. In view of the recent findings of individuality of A antigen expression in kidneys within the A1 and A2 subgroups, an extended typing of A2 donors may be important. The humoral immune response in the recipient may also be dependent on earlier contacts with ABO incompatible pregnancies, vaccinations, or infections. A possible correlation between pre- and posttransplant findings was noted in one case and deserves further notice.

ABO Blood-Group System↗

Conformational analysis of blood group A-active glycosphingolipids using HSEA-calculations. The possible significance of the core oligosaccharide chain for the presentation and recognition of the A-determinant.

Conformational analysis of four different A-active glycosphingolipids, A types 1-4, was carried out using HSEA-calculations with the GESA-program. In their minimum energy conformations the oligosaccharide chains are more or less curved; in particular the type 3 and 4 have a strongly bent shape. When the carbohydrate structures are linked to ceramide, using the conformational features predominantly observed in crystal structures of membrane lipids, rather drastic differences in the orientation of the oligosaccharide chains are obtained. For the type 1 glycosphingolipid the model study indicates that the A-determinant extends almost perpendicularly to the membrane plane whereas for type 2, 3 and 4 the terminal part of the oligosaccharide chains is more parallel to the membrane. The fucose branch on type 3 and type 4 thereby appears directed towards the environment whereas for type 2 it would face the membrane. Due to restrictions imposed by the membrane layer this core specific orientation is largely preserved even if the flexibility of the saccharide-ceramide linkage is taken into account. Hydrophilic and hydrophobic sites on the surface of the different oligosaccharide chains in their minimum energy conformation were located using the GRID-program. It is suggested that the core-dependent presentation of the A-determinant might explain the chain type specificity observed for different monoclonal anti-A antibodies. The results further suggest that assay systems ensuring a membrane-like presentation of the glycolipid antigen should be used in studies of glycolipid/protein interactions.

ABO Blood-Group System↗

Electron ionization mass spectrometry for sequence analysis of glycosphingolipid mixtures by fractional evaporation in the ion source. Mass spectrometric evidence for an eleven-sugar glycolipid.

This paper describes the use of electron ionization mass spectrometry for structural characterization of a mixture of glycosphingolipids from a single human kidney and presents mass spectrometric evidence for the presence of an eleven-sugar glycolipid. A large amount of structural information is obtained from minor glycolipid constituents having long sugar chains by a fractional evaporation in the ion source, achieved by steadily increasing the ion-source temperature.

Carbohydrate Sequence↗

Structures of the eight- to nine-sugar glycolipids of human blood group A erythrocytes.

Two glycolipid fractions, isolated in 1975 from blood group A1 erythrocytes and shown on the basis of direct-inlet mass spectrometry to contain eight- and nine-sugar A-type sequences, have been reinvestigated by fast-atom-bombardment mass spectrometry and overlay analysis with selected monoclonal anti-A antibodies. The presence of three separate glycolipids was concluded, consistent with a common paragloboside backbone [beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-beta-D-Galp-(1----4)-D-Glc] and a typical erythrocyte ceramide component (sphingosine, and 22-, 23-, 24-, and 25-carbon nonhydroxy fatty acids). It is proposed that they carry A determinants based on Type 1 [beta-D-Galp-(1----3)-beta-D-GlcpNAc], Type 2 [beta-D-Galp-(1----4)-beta-D-GlcpNAc], and Type 3 [beta-D-Galp-(1----3)-alpha-D-GalpNAc] chains, respectively. The Type 1 (eight sugars) and Type 3 (nine sugars) glycolipids appeared in mixtures of both the native and the acetylated form. The existence of Type 1 glycolipid, which appears to be a genuine erythrocyte glycolipid as concluded from the ceramide composition, had been predicted earlier by other workers.

ABO Blood-Group System↗

Heterogeneity of anti-A and anti-B monoclonal reagents. Agglutination of some weak ABH erythrocyte variants and recognition of synthetic oligosaccharide and tissue antigens.

Eight anti-A and seven anti-B monoclonal reagents were tested in parallel, with normal and weak ABH red cell phenotypes. A whole range of different reactivity patterns was found, but by making a comparison with the results obtained using polyclonal standard reagents, two major categories of reagents were distinguished: (a) stronger and more specific reagents, and (b) reagents similar to, or weaker than, the standard polyclonal controls. The analysis of the specificity of the reagents by tissue fluorescence staining and reactivity with synthetic oligosaccharides and purified glycolipids confirmed the existence of broad and restricted specificities. Two kinds of anti-A1 reagents are described. One related to type 3/4 structures, which stains the Golgi apparatus, and another with broad anti-A specificity which cross-reacts with 'A-like' structures. The inhibition of anti-A reagents with salivas and synthetic oligosaccharide antigens gave parallel results for the secretor salivas and the difucosylated A antigens.

ABO Blood-Group System↗

Specificity of binding of a strain of uropathogenic Escherichia coli to Gal alpha 1----4Gal-containing glycosphingolipids.

A strain of Escherichia coli originally isolated from urine of a patient with acute pyelonephritis was studied in detail for binding to glycosphingolipids. Bacteria labeled metabolically with [14C]glucose were layered over a glycolipid chromatogram and bound bacteria were detected by autoradiography. The detection was down to a few ng of glycolipid (pmol level) under these assay conditions. At a test level of 500 ng all glycolipids (more than a dozen molecular species analyzed) with Gal alpha 1----4Gal as an internal or terminal part bound the bacteria strongly while glycolipids known to lack this sequence were negative. Conformational analysis using hard sphere calculations including the exo-anomeric effect showed a bend in the saccharide chain at this disaccharide with a largely hydrophobic surface of the convex side, probably being part of the binding epitope. Mixtures of glycolipids isolated from a human ureter scraping and from urinary sediments bound bacteria in the 2- to 7-sugar interval. Thus, this infectious strain of E. coli recognizes glycolipids being present in epithelial cells lining the urinary tract.

ABO Blood-Group System↗

Immunoglobulin subclass (IgG3) restriction of anti-P and anti-Pk antibodies in patients of the rare p blood group.

Serum antibodies against globoside and ceramide trihexoside, two major glycolipids in human erythrocytes, were investigated in 29 individuals with the rare p blood group. Antibodies of the IgM and of the IgG3 classes were detected. In AB Rh(-) blood donors, who were not of the p blood group, low levels of antibodies of the IgM class were found against P and Pk, whereas no antibodies were detected in cord blood. The increased number of spontaneous abortions and stillbirths observed among the p individuals may relate to the presence of IgG3 antibodies, because such antibodies pass the placental barrier and are efficient in complement activation and in mediating antibody-dependent cytotoxicity.

Abortion, Spontaneous↗

Solid-phase biosynthesis on high performance thin-layer plates of blood group glycosphingolipids II.

A new method for the study of carbohydrate chain biosynthesis of amphipathic glycosphingolipids is presented. The method takes advantage of the thin-layer plate which is used as a solid matrix for precursor glycosphingolipids in biosynthetic experiments after chromatographic development of the precursor sample. The method is shown to be simple, fast and sensitive. It minimizes the risk of adding unwanted exogenous precursors and abolishes the need for tedious purification of products after incubation. The method opens up new possibilities for the biosynthetic study of mixtures of glycosphingolipids.

Animals↗

Blood group lewis phenotype on erythrocytes and in saliva in alcoholic pancreatitis and chronic liver disease.

The distributions of ABO, rhesus, and Lewis blood group antigens were studied in patients with alcoholic cirrhosis, alcoholic pancreatitis, chronic active hepatitis, and primary biliary cirrhosis. There were no differences in frequencies of ABO and rhesus blood group antigens between the groups or in comparison with a control group of blood donors. Lewis phenotype Le (a- b-), however, was more common on erythrocytes than in saliva in patients with alcoholic cirrhosis, alcoholic pancreatitis, and severe renal disease but equally common in saliva and on red blood cells in patients with non-alcoholic liver disease. It is suggested that Lewis typing should be performed on saliva because blood typing may give misleading results in some patients.

ABO Blood-Group System↗