Search PubMed⌕ Search

Biomedical subjects

B E Samuelsson

Publications and source records attributed to B E Samuelsson.

At least 19 recordsLinked to original sources
PubMed1992

The blood group B type-4 heptaglycosylceramide is a minor blood group B structure in human B kidneys in contrast to the corresponding A type-4 compound in A kidneys. Structural and in vitro biosynthetic studies.

Blood group A glycolipid antigens have been found based upon at least four different core saccharides (types 1 to 4). The biological significance of this structural polymorphism is not known, although the successful outcome of transplantations of blood group A2 kidneys to blood group O individuals have been partly explained by the low expression of A type-3 and -4 chain glycolipid antigens in A2 kidneys. If graft rejection due to ABO incompatibility is, in any way, correlated to the expression of type-3 and -4 chain blood group glycolipids, it is of interest to identify possible blood group B structures based on these core saccharides. In a non-acid glycosphingolipid fraction isolated from human blood group B kidneys, mass spectrometry, high-temperature gas chromatography-mass spectrometry and probing of thin-layer chromatograms with Gal alpha 1-4Gal-specific Escherichia coli and monoclonal anti-B antibodies provided evidence for minute amounts of a Gal alpha 1-3(Fuc alpha 1-2)Gal beta-HexNAc-Gal alpha 1-4Gal beta-Hex-Ceramide structure consistent with a B type-4 chain heptaglycosylceramide. In contrast, blood group A kidneys have the corresponding A type-4 chain heptaglycosylceramide as the predominant blood group A glycolipid. No, or very low activity of the blood group B gene enzyme on the type-4 chain blood group H hexaglycosylceramide precursor was found by biosynthetic experiments in vitro, which might explain the low expression of type-4 chain blood group B heptaglycosylceramides in human blood group B kidneys.

ABO Blood-Group System↗
PubMed1992

Glycosphingolipid expression in spontaneously aborted fetuses and placenta from blood group p women. Evidence for placenta being the primary target for anti-Tja-antibodies.

A 12-week-old fetus and one 17-week-old fetus + placenta were obtained after spontaneous abortions from two women of blood group p. The 17-week-old fetus was dissected into intestine, liver, brain and residual tissue. Nonacid glycosphingolipid fractions were prepared from the tissues. Glycolipid characterization was carried out using thin layer chromatography immunostained with monoclonal antibodies and bacteria and by 1H NMR spectroscopy and mass spectrometry. In the placental fraction substantial amounts of globotetraosylceramide (P-antigen) and globotriaosylceramide (Pk-antigen) were identified. In contrast, the fetuses contained only trace amounts of these structures, as revealed by immunostaining. These results indicate that the primary target for the antibodies of the anti-Tja serum is the placenta tissue, resulting in termination of the pregnancy.

Abortion, Spontaneous↗
PubMed1992

Characterisation of the anti-A antibody response following an ABO incompatible (A2 to O) kidney transplantation.

Anti-A,B antibodies produced in a blood group OLe(a-b-) recipient receiving a kidney graft from a blood group A2Le(a-b+) donor have been analysed for their ability to bind to different glycosphingolipid antigens. Solid-phase RIA using pure glycosphingolipid antigens and a chromatogram binding assay using total nonacid glycosphingolipid fractions from erythrocytes of different human blood group phenotypes together with pure glycolipid antigens were used as assay systems. Serum antibodies were shown to bind equally well to A (types 1, 2, 3 and 4) and B (types 1 and 2) antigenic structures but no binding to H antigens (types 1, 2 and 4) was detected. After adsorption of serum antibodies on A1 Le(a-b+) erythrocytes there was a residual anti-A antibody activity which could not be adsorbed by synthetic A-trisaccharides coupled to crystalline silica (Synsorb-A). These residual antibodies, which are not present in a pretransplant serum sample, had a specificity for the A antigen with type 1 core saccharide chain and the binding epitope obviously included both the N-acetylgalactosamine and the N-acetylglucosamine. The fucose residue was apparently not obligate for binding. The conformation of the sugar units involved in the binding epitope was determined.

ABO Blood-Group System↗
PubMed1992

Serological and immunochemical characterization of anti-PP1Pk (anti-Tja) antibodies in blood group little p individuals. Blood group A type 4 recognition due to internal binding.

Serum samples from 13 blood group little p individuals were tested by radioimmunoassay for their IgG antibody subclass distribution against the P, P1 and Pk antigens. There was no uniform subclass distribution pattern, although all but one had IgG3 antibodies against all the P system antigens tested. Studies were performed adsorbing anti-Tja serum sequentially to columns with synthetic carbohydrate antigenic determinants within the P system coupled to silica beads (SynsorbsR). The effect on agglutinin and indirect antiglobulin titers was determined after adsorption to SynsorbsR with different P-system antigens (P1, Pk, P). Adsorption to all the three SynsorbsR was needed to eliminate or strongly reduce antibody titers. The effect on IgM, IgG, IgA as well as IgG subclass antibody binding to P, P1 and Pk antigens was also determined by radioimmunoassay and chromatogram binding assay. Anti-PP1Pk antibodies from a little p woman with repeated abortions were shown to bind to glycosphingolipid antigens prepared from one of the aborted placentae using a chromatogram binding assay. This binding was eliminated by serum adsorption to SynsorbsR with P1, Pk and P carbohydrates. Anti-PP1Pk antibodies were also shown to bind to extended structures in the globoseries, i.e. globopentaosylceramide, globohexaosylceramide (globo-H) and globoheptaosylceramide (globo-A). This binding is most probably due to antibodies recognizing internal sequences in the carbohydrate chain. Attempts were made to visualize the binding epitope of the antibodies by computer molecular modelling.

Adult↗
PubMed1992

Alterations of glycosphingolipid-based blood group antigen expression on erythrocytes and in plasma studied on consecutive samples after a blood group O to A bone marrow transplantation.

A blood group A1Le(a-b+) individual with chronic myeloid leukaemia had received a bone marrow graft from an HLA-identical OLe(a+b-) donor. Twelve months after bone marrow transplantation (BMT), the red blood cells of the patient became agglutinable with anti-A blood group reagents. To elucidate whether the blood group A antigen expression was of plasma or of bone marrow origin, total non-acid glycosphingolipid fractions were prepared from red blood cells and plasma collected 17 months after BMT, and from plasma collected 13, 15 and 19 weeks after BMT. The glycolipid fractions were analysed by thin-layer chromatography and immunostained with monoclonal A-antibodies, and permethylated and permethylated-reduced derivatives of selected plasma samples were analysed by mass spectrometry. The results strongly indicate the presence of host bone marrow-produced blood group A red blood cells. Furthermore, the presence of a blood group H active pentaglycosylceramide type 1 (H-5-1) (Table I), characteristic for an OLe(a-b-) secretor, was seen in plasma 3-4 weeks before clinical chronic graft versus host disease (GVHD). After treatment of chronic GVHD, this expression disappeared. The blood group ALeb (A-7-1) antigen produced by the recipient seems to be present and to increase with time in all plasma samples. This also seems to be the case for the Leb and A-6-1 antigens.

ABO Blood-Group System↗
PubMed1992

Non-acid glycosphingolipid expression in plasma of an A1 Le(a-b+) secretor human individual: identification of an ALeb heptaglycosylceramide as major blood group component.

Total non-acid glycosphingolipids were isolated from plasma of an A1 Le(a-b+) secretor individual with Refsum's disease (phytanic acid storage disease). The glycolipids were separated into 11 fractions by open column chromatography and by HPLC. The fractions were analyzed by thin-layer chromatography and tested for different blood group A activities as well as blood group Le(a )and Leb activity. The fractions were structurally characterized by proton NMR spectroscopy and FAB mass spectrometry and in selected cases by EI mass spectrometry of the permethylated and permethylated-reduced derivatives. Degradation analysis was performed on partially permethylated or permethylated-reduced alditol acetates. The dominating blood group compound was found to be a blood group A active type 1 chain difucosylheptaglycosylceramide. Other blood group compounds were identified as a blood group A active type 1 chain monofucosylhexaglycosylceramide, a blood group Leb hexaglycosylceramide, a blood group H active type 1 chain pentaglycosylceramide, and a globotetraosylceramide (the P-antigen). The presence of a Le(a) glycosphingolipid and blood group A type 3/4 chain structures were also found by immunostaining. Glucosyl-, lactosyl-, and globotriaosylceramides were the dominating short chain compounds. The amount of phytanic acid incorporated into the monoglycosylceramide fraction was found to be less than 5% of the fatty acids.

Animals↗
PubMed1992

Basic biochemistry of cell surface carbohydrates and aspects of the tissue distribution of histo-blood group ABH and related glycosphingolipids.

Cell surface carbohydrates may be protein- or lipid-linked. The structural polymorphism of the oligosaccharide chains is extensive due to variations in monosaccharide composition, carbohydrate sequence, branching, linkage position and linkage anomericity. Blood group ABH and related glycosphingolipids show a remarkable tissue-specific expression with possible implications in areas such as transfusion medicine, transplantation surgery and oncology. This communication gives a condensed description of the present knowledge of the tissue-specific distribution of histo-blood glycolipids in humans.

ABO Blood-Group System↗
PubMed1991

Blood group type glycosphingolipids of human kidneys. Structural characterization of extended globo-series compounds.

Blood group type glycosphingolipids present in kidneys of blood group A and B human individuals have been isolated and structurally characterized by mass spectrometry, proton NMR spectroscopy, degradation studies and by their reactivity with various monoclonal antibodies and Escherichia coli bacteria. The two major complex glycolipids present in the blood group A and B kidneys were globopentaosylceramide (IV3Gal beta-Gb4Cer) and the X pentaglycosylceramide (III3Fuc alpha-nLc4Cer). The major blood group A glycolipid in the blood group A kidneys was based on the type 4 chain (globo-series). There were also small amounts of the type 2 chain and trace amounts of the type 1 and type 3 chain based A glycolipids. In addition, the blood group H type 4 chain structure was present together with Le(a) and Le(b) compounds. In the blood group B kidneys, the major B glycolipids were monofucosylated hexa- and octaglycosylceramides, where the former were based on the type 2 carbohydrate chain. The blood group B type 4 chain heptaglycosylceramide was found to be a minor component making up only about 1% of the total blood group B structures.

ABO Blood-Group System↗
PubMed1990

Blood group A glycolipid antigen expression in kidney, ureter, kidney artery, and kidney vein from a blood group A1Le(a-b+) human individual. Evidence for a novel blood group A heptaglycosylceramide based on a type 3 carbohydrate chain.

Kidney, ureter, kidney artery, and kidney vein tissue were obtained from a single human transplant specimen. The donors erythrocyte blood group phenotype was A1Le(a-b+). Total non-acid glycolipid fractions were isolated and individual glycolipid components were identified by immunostaining thin layer plates with a panel of monoclonal antibodies and by mass spectrometry of the permethylated and permethylated-reduced total glycolipid fractions. The dominating glycolipids in all tissues were mono- to tetraglycosylceramides. In the kidney, ureter, and artery tissue less than 1% of the glycolipids were of blood group type, having more than 4 sugar residues. In contrast, 14% of the vein glycolipids were of blood group type, and the dominating components were type 1 chain blood group H pentaglycosylceramides and A hexaglycosylceramides. Trace amounts of structurally different blood group A glycolipids (type 1 to 4 core saccharide chains) with up to 10 sugar residues were found in the kidney, ureter, and vein tissues, including evidence for a novel blood group A heptaglycosylceramide based on the type 3 chain in the vein. The only detected A glycolipid antigen in the artery tissue was the blood group A difucosyl type 1 chain heptaglycosylceramide (ALeb) structure. Blood group Lewis and related antigens (Lea, Leb, and ALeb) were expressed in the kidney, ureter, and artery, but were completely lacking in the vein, indicating that the Le gene-coded alpha 1-4-fucosyltransferase was not expressed in this tissue. The X and Y antigens (type 2 chain isomers of the Lea and Leb antigens) were detected only in the kidney tissue.

ABO Blood-Group System↗
PubMed1990

Glycolipid- and glycoprotein-based blood group A antigen expression in human thrombocytes. A1/A2 difference.

Total non-acid glycolipid fractions and total sodium dodecylsulphate (SDS) solubilized protein fractions were isolated from human thrombocytes obtained from single human donors having different blood group A1/A2 phenotypes. The blood group A glycolipid antigens were characterized by immunostaining of thin layer plates with different monoclonal anti-A antibodies. The glycoproteins carrying blood group A epitopes were identified by SDS-PAGE and Western blot analysis using a monoclonal anti-A antibody. Blood group A glycolipid antigens were found in both A1 and A2 thrombocytes but the A2 individuals expressed at least ten times less A glycolipids compared to the A1 individuals. Expression of A type 3/4 chain and small amounts of A type 1 chain glycolipids were seen in thrombocytes of both A1 and A2 individuals, while the type 2 chain A glycolipids appeared to be missing from the A2 thrombocytes. Blood group A reactive glycoproteins were only found in thrombocytes of A1 individuals and could not be detected in A2 individuals or a blood group O individual. The major blood group A glycoprotein were found as a double band migrating in the 130 kDa region.

ABO Blood-Group System↗
PubMed1990

Blood group A glycolipid antigen biosynthesis: discrimination between biosynthesized and enzyme preparation derived blood group A antigen by mass spectrometry.

A monofucosyl type 1 chain blood group A hexaglycosylceramide was biosynthesized in solution using the type 1 chain blood group H pentaglycosylceramide as precursor, a crude microsomal fraction prepared from the mucosa scraping of a blood group A pig small intestine as enzyme source, and uridine diphosphate-N-acetyl-(1-14C)galactosamine as sugar donor. The radioactive product was enriched using reversed-phase column chromatography and silica gel HPLC. The peak, as detected by a beta-flow scintillation counter, was collected, permethylated, and analyzed by mass spectrometry. Carbohydrate sequence ions were found, indicating the presence of both the biosynthesized and a native, non-14C-containing blood group A hexaglycosylceramide. The blood group A pig small intestinal mucosa used as the enzyme source contain blood group A hexaglycosylceramide as the predominant glycolipid. Therefore, it is concluded that the nonradioactive blood group A hexaglycosylceramide found after the biosynthesis is derived from the enzyme preparation.

ABO Blood-Group System↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗