Biomedical subjects

B Cedergren

Publications and source records attributed to B Cedergren.

At least 19 recordsLinked to original sources

PubMed2000

Cloning and expression of the histo-blood group Pk UDP-galactose: Ga1beta-4G1cbeta1-cer alpha1, 4-galactosyltransferase. Molecular genetic basis of the p phenotype.

The molecular genetic basis of the P histo-blood group system has eluded characterization despite extensive studies of the biosynthesis of the P(1), P, and P(k) glycolipids. The main controversy has been whether a single or two distinct UDP-Gal:Galbeta1-R 4-alpha-galactosyltransferases catalyze the syntheses of the structurally related P(1) and P(k) antigens. The P(1) polymorphism is linked to 22q11.3-ter. Data base searches with the coding region of an alpha4GlcNAc-transferase identified a novel homologous gene at 22q13.2 designated alpha4Gal-T1. Expression of full coding constructs of alpha4Gal-T1 in insect cells revealed it encoded P(k) but not P(1) synthase activity. Northern analysis showed expression of the transcript correlating with P(k) synthase activity and antigen expression in human B cell lines. Transfection of P(k)-negative Namalwa cells with alpha4Gal-T1 resulted in strong P(k) expression. A single homozygous missense mutation, M183K, was found in six Swedish individuals of the rare p phenotype, confirming that alpha4Gal-T1 represented the P(k) gene. Sequence analysis of the coding region of alpha4Gal-T1 in P(1)+/- individuals did not reveal polymorphisms correlating with P(1)P(2) typing.

Amino Acid Sequence↗

PubMed1996

Histo-blood group p: biosynthesis of globoseries glycolipids in EBV-transformed B cell lines.

The genetic and biosynthetic basis of the histo-blood group P-system is not fully understood. Individuals with the rare p phenotype do not express the three glycolipid antigens (Pk, P and P1) of this system, probably because of deficiencies in glycosyltransferases involved in their biosynthesis. Iiuka et al. [Iiuka S, Chen SH, Yoshida A (1986) Biochem Biophys Res Commun 137: 1187-95], however, previously reported that detergent extracts from an EBV-transformed B cell line derived from a p individual did express the glycosyltransferase activity (Pk transferase) assumed to be missing in this blood group status. Here, we have reinvestigated the antigen expression and glycosyltransferase activities in two p individuals by analysing EBV-transformed cell lines as well as erythrocytes to confirm the blood group P status. The thin layer chromatography glycolipid profile of extracts from erythrocytes and EBV-transformed B cell lines showed characteristic accumulation of lactosylceramide and absence of Pk and P antigens. Glycosyltransferase activities of the B cell lines were analysed using glycolipid substrates and both extracts were found to contain lactosylceramide synthetase and P transferase activities but to be completely devoid of Pk transferase activity. The presented data indicate that p individuals, in contrast to previous reports, do not express a functional Pk glycosyltransferase.

Antigens, Surface↗

PubMed1993

A point mutation in the GYPC gene results in the expression of the blood group Ana antigen on glycophorin D but not on glycophorin C: further evidence that glycophorin D is a product of the GYPC gene.

Glycophorin C (GPC) and glycophorin D (GPD) are homologous sialoglycoproteins in the human red blood cell membrane. Both are thought to be encoded by the GPC gene (GYPC). We report that the rare blood group antigen, Ana, is expressed on GPD but not on GPC. cDNA was synthesized from total RNA obtained from two unrelated, heterozygous Ana+ blood donors and analyzed by the polymerase chain reaction using primers that spanned sequences encoded by the GYPC gene. The expected 412-bp fragment was generated, and sequencing of the amplified product showed a G-->T substitution at nucleotide 67 of the coding sequence, resulting in the substitution of alanine by serine at amino acid residue 23 of GPC and, presumably, residue 2 of GPD. To explain the expression of Ana on GPD but not on GPC, we postulate that the conformation of the amino acid residues at the N-terminal region of GPD determines the antigenic expression as this conformation would be different from that of the same sequence of amino acids occurring within GPC. Other possible reasons for antigen expression on a shorter protein product but not on the full-length protein product of the same gene are discussed. We extrapolate this reasoning to account for the expression of the common GE2 blood group antigen on GPD but not on GPC.

Amino Acid Sequence↗

PubMed1992

Structural characterization of x2 glycosphingolipid, its extended form, and its sialosyl derivatives: accumulation associated with the rare blood group p phenotype.

It has been suggested that the x2 glycosphingolipid (GSL) could offer a structural basis for a P-like antigen activity found in blood group p individuals [Kannagi R., Fukuda, M.N., Hakomori, S. (1982) J. Biol. Chem. 257, 4438]. The structures of the x2 and sialosyl-x2 GSLs have been confirmed unequivocally as shown below by +FAB-MS, methylation analysis by GC-MS, and 1H-NMR. We have established a [formula: see text] monoclonal antibody (TH2) specific for the GalNAc beta 1----3Gal beta 1----4GlcNAc epitope, the terminal trisaccharide of x2 GSL. Application of MAb TH2 on TLC immunoblotting together with chemical analysis indicates the following points of interest: (i) the existence of extended type GSLs having the same x2 terminal structure; (ii) the chemical quantities of x2, sialosyl-x2, and extended x2 found in blood cells and in various tissues including carcinomas being nearly the same; (iii) considerably larger quantities of x2 and x2-derived structures found in blood samples of rare blood group p individuals. The accumulation of x2 and its derivatives in blood cells of p individuals is in contrast to the occurrence of these GSLs as extreme minor components in normal human red blood cells and tissues, and they may be responsible for the reported P-like activity in blood group p individuals [Naiki, M., & Marcus, D. M. (1977) J. Immunol. 119, 537].

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

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↗

PubMed1989

Genetic genealogical studies of 20 north Swedish families with the rare blood group p.

In the county of Västerbotten in northern Sweden, a large number of individuals with the rare blood group p have been found. The ancestors of all known 31 cases were studied genealogically, and the data showed that about one half of all cases (15 out of 31 in 9 out of 20 families) could be traced to one gene source in the north-eastern part of the county in the middle of the 17th century. In two of the families the parents were first cousins and in three they were second cousins. In the 18th and 17th centuries genealogical connections between the parents were found in another 10 of the families.

Adult↗

PubMed1989

HLA antigens, blood groups and serum protein groups in patients with intermittent claudication.

HLA (A and B) antigens, blood group systems (AB0, Rh, MNSs P, Kell, Lewis and Duffy) and serum group systems (Hp, Tf, Pi, C3 and C4) were studied in patients with intermittent claudication (IC) and controls. HLA antigen A 28 was significantly more common, and blood group 0 was significantly less common among the patients than among the controls. A comparison between patients with IC and those with abdominal aortic aneurysms showed a significant difference between these two groups concerning the MN blood groups.

Adult↗

PubMed1988

Globo-A--a new receptor specificity for attaching Escherichia coli.

Uropathogenic Escherichia coli strains designated as ONAP, based on their O negative A positive agglutination of human P1 erythrocytes, were shown to prefer the globo-A glycolipid as a receptor structure. The dependence on both the A terminal and the globoseries chain was confirmed by agglutination of human AP1, but not Ap or OP1 erythrocytes and by binding to the globo-A glycolipid on TLC plates. Neither Gal alpha 1----4Gal beta nor the A trisaccharide GalNAc alpha 1----3(Fuc alpha 1----2)Gal beta alone functioned as receptors. The bacteria thus appeared to recognize an epitope resulting from the combination of the terminal and internal structures.

Animals↗

PubMed1988

Population studies in northern Sweden. XIV. Variation of the A1A2B0 blood group gene frequencies.

Frequencies of the A1A2B0 blood group genes were studied in a material of 5,632 conscripts and blood donors from the counties of Norrbotten and Västerbotten in northern Sweden. The individuals were distributed according to place of birth into 23 subpopulations. In northern Sweden different clines were found for the A1, A2 and 0 genes. The frequencies of the A1 and A2 genes were increasing in the northeastern respectively northern direction, and the frequency of the 0 gene was increasing in the southwestern direction. These geographical patterns could be explained in terms of Finnish and Lappish influence.

ABO Blood-Group System↗

PubMed1987

Cryoprecipitate infusion fails to improve organ function in septic shock.

Plasma fibronectin may be of critical importance for the septic patient through its proposed function as the major opsonin for macrophage clearance of circulating, noncellular debris. As a rule, critically ill, septic patients are depleted of fibronectin. In earlier uncontrolled studies, infusion of fibronectin-rich cryoprecipitate had resulted in improved renal and pulmonary functions and changes in peripheral hemodynamics. In this controlled study, 32 septic ICU patients (mean initial fibronectin level = 60% of normal) received cryoprecipitate or control infusions. Although the fibronectin level was significantly elevated to the normal range in the cryoprecipitate group, no effects were seen in hemodynamics, oxygen metabolism, or lung and kidney functions. Our results indicate that this form of fibronectin therapy does not influence the impaired organ function in septic shock.

Adult↗

PubMed1987

Receptor-specific agglutination tests for detection of bacteria that bind globoseries glycolipids.

Specific binding to the globoseries of glycolipid receptors explains the adherence of uropathogenic Escherichia coli to host cells. The minimal receptor disaccharide Gal alpha 1----4Gal beta [galactose alpha (1----4)galactose beta] is recognized by most attaching clinical isolates. However, wild-type isolates can express adhesins with several different receptor specificities. Bioassays do not permit separate analysis of each receptor specificity, since the target cells contain multiple potentially receptor-active molecules. In this study, bacterial adhesins were analyzed by using receptors immobilized into latex beads in one of two ways. In one way, di- and trisaccharides were covalently linked via a spacer arm to latex beads coupled with bovine serum albumin. In the other way, receptor-active glycolipids were coated onto the bovine serum albumin-latex beads. The latex beads were subsequently used for agglutination by using type strains with known receptor specificity. The composition was optimized regarding receptor structure and size of latex beads. Gal alpha 1----4Gal beta was as active as the trisaccharide derivative Gal alpha 1----4Gal beta 1----3glucose or Gal alpha 1----4Gal beta 1----3glucosamine. Among the natural glycolipids tested, globotetraosylceramide was the most active. Subsequently, the sensitivity and specificity of the Gal alpha 1----4Gal beta-latex and globotetraosylceramide-latex reagents were compared for 733 E. coli urinary isolates. Hemagglutination of human erythrocytes was used as the positive standard. No significant difference in the specificity or sensitivity of the latex reagents was found; the sensitivity ranged from 86%, when isolates agglutinating human erythrocytes of blood groups P1 and p were included, to 93%, when those isolates agglutinating erythrocytes of blood group p were excluded. These reagents provide tools for bacterial identification in patients with urinary tract infection.

Adhesins, Escherichia coli↗

PubMed1987

Genetic markers in patients with intracranial aneurysms.

HLA antigens, blood group systems (ABO, Rh, MNSs, P, Kell, Lewis and Duffy) and serum group systems (Hp, Tf, Gc, Pi, Bf, C3 and C4) were studied in a series of patients with intracranial aneurysms. A significantly increased frequency of HLA antigen A28, a significantly decreased frequency of HLA antigen B40, and a significantly decreased frequency of complement factor C4 B2 was found among the patients when compared with controls from the same geographic area.

Complement C4↗

PubMed1986

Influence of blood group on the availability of receptors for attachment of uropathogenic Escherichia coli.

Escherichia coli strains with defined receptor specificity were used as probes to analyze the individual variation in host cell receptors with respect to blood groups. The adhesins were initially characterized as mannose sensitive (MS), mannose resistant (MR), or nonagglutinating (-). The receptor specificity of the strains with MR adhesins was defined by agglutination of synthetic Gal alpha 1----4Gal beta covalently linked via a spacer arm, (CH2)2S(CH2)2CO approximately H-bovine serum albumin (BSA) to BSA-latex beads as specific for the globoseries glycolipid receptors (MR:GS). Strains with MR adhesins not reacting with Gal alpha 1----4Gal beta-BSA-latex were designated MR:nonGS. The attachment and hemagglutination of the MR:GS strains was strictly dependent on Gal alpha 1----4Gal beta-containing receptors, as shown by the absence of binding to cells from individuals of blood group P lacking these structures. Previous reports showed differences in the composition of globoseries glycolipids between erythrocytes from individuals of P1 and P2. No significant difference was found, However, in the mean adhesion to P1 and P2 epithelial cells or in the agglutination titer for P1 and P2 erythrocytes. The MR:GS receptors were equally distributed on squamous and transitional epithelial cells. In contrast, the distribution of MR:nonGS receptors was skewed. Attachment occurred mostly to squamous epithelial cells. The attachment of strains with MR:nonGS adhesins was independent of the P blood group of the cell donor. The binding ability of MR:GS and MR:nonGS adhesins appeared independent and additive. The attachment was not influenced by the ABH blood group. However, increased binding to epithelial cells from nonsecretors occurred regardless of the P blood group, suggesting a shielding of receptors by products controlled by the secretor genes. These results illustrate how individual variation in cell surface components with and without receptor activity determine the interaction of a ligand with a known receptor.

Adhesins, Escherichia coli↗

PubMed1985

Transferrin C subtypes and occupational photodermatosis of the face.

In a factory in northern Sweden where 120 workers were uniformly exposed to photoactive substances 73 developed occupational facial eczema while 47 showed no reaction. The workers were examined with respect to 16 genetic marker systems: HLA, blood groups (ABO, Rh, MNSs, P, K, Le and Fy) and serum groups (Hp, Tf, Gc, Pi, Bf, C3, C4 and C6). Between reactors and nonreactors the following differences were found: (1) a significant decrease (p less than 0.05) of HLA A11 among the reactors; (2) a significant increase (p less than 0.05) of the C3 FS type among the reactors; (3) a highly significant increase (p less than 0.001) of the transferrin C2 gene and of the C2 variant among the reactors. The association with Tf C2 remained significant also after correction for number of significance tests. Since transferrin (iron) is known to catalyze the formation of hydroxyl radicals we hypothesize that the Tf C2 variant is more efficient in promoting radical formation and thereby cell damage. Other results supporting the notion that transferrin C2 may be associated with an increased susceptibility to toxic damage are discussed.

Blood Group Antigens↗

PubMed1985

Fibronectin and other DIC-related variables in patients with moderately severe infections receiving cryoprecipitate.

Plasma fibronectin (Fn), a glucoprotein of suggested importance in host defence during infections also seems to be involved in blood coagulation and to be consumed during clot formation. Low Fn concentrations have been found in patients with DIC, but also in patients with infections without signs of overt DIC. In a randomized trial of Fn supplementation 28 patients with moderately severe infections, hospitalized in the Department for Infectious Diseases, were scheduled to receive either cryoprecipitate from 30 donors (n = 14) or 250-300 ml of stored plasma (n = 14). To elucidate the relationship between Fn plasma levels, Fn-rich cryoprecipitate infusion, and possible low-grade DIC in these patients, we measured platelet count, prothrombin complex (NT), fibrinogen, F V, F VIIIR:Ag, F VIII:C, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin III (AT), kallikrein-inhibiting activity (KI) and spontaneous proteolytic activity (SPA). Compared to healthy controls, high initial values (p less than .001) were found for fibrinogen, F VIIIR:Ag, F VIII:C and SPA. Most values for platelets, F V, Plg, AP and KI were within the reference range. Low levels (p less than .001) were found for Fn, NT, F XII, AT and for the ratio F VIII:C/F CIIIR:Ag. A significant correlation was found between F XII, Plg and AT. Fn correlated poorly to the other variables. Cryoprecipitate infusion normalized the Fn concentration, but had no influence on other measured variables. Thus, although no patient had clinically overt DIC, and all survived, we observed a distinct pattern indicating activation of the coagulation system. Fn levels were low, but were not specifically related to this activation.

Adult↗

PubMed1985

Fibronectin and other DIC-related variables in septic ICU patients receiving cryoprecipitate.

In a controlled study of fibronectin supplementation in sepsis, 11 ICU patients in septic shock were scheduled to receive either cryoprecipitate from 20-40 donors (n = 6) or 250-300 ml of stored plasma (n = 5) (two infusions over 24 h). We wanted to: compare some "conventional" DIC variables in the ICU (platelet count, prothrombin complex = NT, FDP) to additional variables: Fibronectin (Fn), fibrinogen (Fg), F V, FVIII R:Ag, F VIII:C activity, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin (AT), kallikrein inhibiting activity (KI) and spontaneous proteolytic activity (SPA): study the effects of cryoprecipitate or plasma infusion on three variables. Samples were taken before the first infusion, and 24 and 48 h after. At onset, high levels (p less than .001 when compared to blood donors) of Fg, VIIIR:Ag and VIII:C were seen. KI levels were within the normal range. F V was low (p less than .05). Fn, NT, XII, Plg, AP and AT were markedly low (p less than .001). SPA showed great variation. When compared to 28 patients with severe infections, but not in septic shock, the ICU group had higher VIIIR:Ag (p less than .05) and VIII:C (p less than .01), and lower XII, Plg, AP and AT (p less than .001). FDP was elevated in all ICU patients. Five patients were thrombocytopenic, and in these a pattern with low levels of Plg and AT was observed. Fn did not correlate well to the other variables measured. These results indicate a marked activation of coagulation and fibrinolysis in these severely ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

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↗