Search PubMed⌕ Search

Biomedical subjects

M J Tanner

Publications and source records attributed to M J Tanner.

At least 109 records · Page 6Linked to original sources
PubMed1985

Abnormal minor human erythrocyte membrane sialoglycoprotein (beta) in association with the rare blood-group antigen Webb (Wb).

Individuals whose erythrocytes are positive for the rare blood-group antigen Webb (Wb) have an altered form of the minor sialoglycoprotein beta (synonyms glycophorin C and glycoconnectin). This altered sialoglycoprotein beta (beta Wb) has an Mr about 2700 lower than that of normal sialoglycoprotein beta. Treatment of normal sialoglycoprotein beta with endo-beta-N-acetylglucosaminidase F decreased its Mr by about 3600, but similar treatment of sialoglycoprotein beta Wb had no effect. These results suggest the possibility that sialoglycoprotein beta Wb lacks the N-glycosidically linked oligosaccharide found on normal sialoglycoprotein beta.

Blood Group Antigens↗
PubMed1985

The phospholipid organisation in the membranes of McLeod and Leach phenotype erythrocytes.

The phospholipid composition, the distribution of phospholipids over the two membrane layers as well as the phosphatidylcholine-specific transfer protein-mediated exchangeability of phosphatidylcholine from the membrane, has been investigated in two types of abnormal erythrocytes--the McLeod phenotype and the Leach phenotype. The acanthocytic McLeod cells appeared to have a normal phospholipid composition and distribution, but the exchangeability of phosphatidylcholine was found to be markedly enhanced. Unlike control erythrocytes, in which 75% of all of the phosphatidylcholine can be exchanged during an 8 h incubation, the McLeod cell showed a complete exchange of this phospholipid within the same time period. This obviously indicates an enhanced transbilayer mobility of phosphatidylcholine in the membrane of McLeod cells. Erythrocytes of the Leach phenotype showed an elliptocytic shape and increased osmotic fragility, but no abnormalities were observed as to the composition and organisation of the phospholipid complement of their membranes.

Erythrocyte Membrane↗
PubMed1984

The Rhesus (D) polypeptide is linked to the human erythrocyte cytoskeleton.

Cytoskeleton preparations derived from lactoperoxidase-radioiodinated human erythrocytes were found to be enriched in a labelled component with the same apparent molecular mass as the Rhesus (D) (Rh(D] antigen polypeptide. Immune precipitation from the cytoskeleton preparations confirmed that this component is the Rh(D) polypeptide. The results suggest that the Rh(D) polypeptide may be linked to the erythrocyte skeletal matrix. The possibility that the Rh(D) antigen is involved in maintaining the shape and viability of the erythrocyte is discussed.

Erythrocyte Membrane↗
PubMed1984

Rhnull human erythrocytes have an abnormal membrane phospholipid organization.

Rhnull human erythrocytes lack the antigens of the Rhesus blood group system, have an abnormal shape and an increased osmotic fragility, and are associated with mild chronic haemolytic anaemia. Studies with phospholipase A2 and sphingomyelinase C show that the asymmetric distribution of phosphatidylethanolamine (PtdEtn) in the membrane of these cells differs from that found in control cells. The amount of PtdEtn which can be hydrolysed by phospholipase A2 in the presence of sphingomyelinase C in intact Rhnull cells is twice as high as that in normal erythrocytes. In intact Rhnull cells all of the phosphatidylcholine (PtdCho) present in the membrane can be readily exchanged with a PtdCho-specific exchange protein, whereas in control cells 75% is readily exchanged and 25% at a much lower rate. This indicates that PtdCho experiences a relatively fast transbilayer movement in the Rhnull cells. The observation that the loss of two membrane polypeptides in the Rhnull cells leads to abnormal shape, increased osmotic fragility, abnormal PtdEtn distribution and enhanced transbilayer mobility of PtdCho strongly suggests that one or both polypeptides are essential for the maintenance of a proper membrane-membrane skeleton interaction.

Erythrocyte Membrane↗
PubMed1984

Individuals lacking the Gerbich blood-group antigen have alterations in the human erythrocyte membrane sialoglycoproteins beta and gamma.

Membranes from erythrocytes with a new Gerbich (Ge)-negative phenotype (Leach phenotype), as well as those from two other Ge-negative phenotypes, were examined. Whereas cells of the Leach phenotype apparently lack three minor sialoglycoproteins (beta, beta 1 and gamma), the membranes of Ge- Yus- and Ge- Yus+ erythrocytes apparently lack beta- and gamma-sialoglycoproteins but contain additional diffusely migrating components of apparent Mr 30 500-34 500 and 32 500-36 500 respectively. Immunoprecipitation experiments showed that the abnormal components of both Ge- Yus- and Ge- Yus+ erythrocytes reacted with two monoclonal antibodies, BRIC 4 and BRIC 10. These antibodies have been shown to react with sialoglycoproteins beta and beta 1 in normal erythrocytes. Cytoskeletal preparations from Ge- Yus- and Ge- Yus+ erythrocyte membranes contained the abnormal components. In contrast with cells of the Leach phenotype, which are elliptocytic, Ge- Yus- and Ge- Yus+ were of normal shape, despite their apparent lack of beta- and gamma-sialoglycoproteins. It seems likely that the abnormal components in these cells contribute to their normal shape. Ovalocytic erythrocytes were shown to incorporate more radioactivity in the sialoglycoprotein-beta 1 region than normal erythrocytes after labelling by the periodate/NaB3H4 technique. It is suggested that abnormal components in Ge- Yus- and Ge- Yus+ erythrocytes result from chromosomal misalignment with unequal crossing-over at meiosis between the genes giving rise to beta-, beta 1- and gamma-sialoglycoproteins.

Antibodies, Monoclonal↗
PubMed1984

Two individuals with elliptocytic red cells apparently lack three minor erythrocyte membrane sialoglycoproteins.

We have studied the erythrocytes of two individuals (P. L. and K. W.) who lack the Gerbich (Ge) blood-group antigen. The erythrocytes of P. L. and K. W. were not reactive with two monoclonal antibodies (NBTS/BRIC 4 and NBTS/BRIC 10) which reacted with normal erythrocytes. The membranes of P. L. and K. W. erythrocytes appeared to lack three minor sialoglycoproteins (beta, beta 1 and gamma). These three minor sialoglycoproteins were found to be associated with the cytoskeletons of normal erythrocytes. Approx. 10% of the erythrocytes of P. L. and K. W. were frankly elliptocytic. We suggest that one or more of the minor sialoglycoproteins may play a part in maintaining the discoid shape of the human erythrocyte.

Blood Group Antigens↗
PubMed1983

The human erythrocyte anion-transport protein. Partial amino acid sequence, conformation and a possible molecular mechanism for anion exchange.

The N-terminal 72 residues of an integral membrane fragment, P5, of the human erythrocyte anion-transport protein, which is known to be directly involved in the anion-exchange process, was shown to have the following amino acid sequence: Met-Val-Pro-Lys-Pro-Gln-Gly-Pro-Leu-Pro-Asn-Thr-Ala-Leu-Leu-Ser-Leu-Val-Leu-Met -Ala-Gly-Thr-Phe-Phe-Phe-Ala-Met-Met-Leu-Arg-Lys-Phe-Lys-Asn-Ser-Ser-Tyr-Phe-Pro-Gly-Lys-Leu-Arg-Arg-Val-Ile-Gly-Asp-Phe-Gly-Val-Pro-Ile-Ser-Ile-Leu-Ile-Met-Val-Leu-Val-Asp-Phe-Phe-Ile-Gln-Asp-Thr-Tyr-Thr-Gln- The structure of this fragment was analysed, with account being taken of the constraints that apply to the folding of integral membrane proteins and the topographical locations of various sites in the sequence. It was concluded that this sequence forms two transmembrane alpha-helices. These are probably part of a cluster of amphipathic transmembrane alpha-helices, which could comprise that part of the protein responsible for transport activity. The presently available evidence relating to the anion-exchange process was considered with the structural features noted in this study and a possible molecular mechanism is proposed. In this model the rearrangement of a network of intramembranous charged pairs mediates the translocation of an anion between anion-binding regions at each surface of the membrane, which are composed of clusters of positively charged amino acids. This model imposes a sequential exchange mechanism on the system. Supplementary material, including Tables and Figures describing the compositions of peptides determined by amino acid analysis and sequence studies, quantitative and qualitative data that provide a residue-by-residue justification for the sequence assignment and a description of modifications to and use of the solid-phase sequencer has been deposited as Supplementary Publication SUP 50123 (12 pages) with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained as indicated in Biochem. J. (1983) 209, 5.

Amino Acid Sequence↗
PubMed1983

Absence of two membrane proteins containing extracellular thiol groups in Rhnull human erythrocytes.

Rhnull human erythrocytes lack all the antigens of the Rhesus blood-group system and are associated with mild chronic haemolytic anaemia. These erythrocytes have an abnormal shape and increased osmotic fragility. Labelling studies with the impermeant maleimide N-maleoylmethionine [35S]sulphone show that Rhnull erythrocytes lack two extracellular thiol-group-containing membrane components of apparent mol.wts. 32 000 and 34 000. Immunoprecipitation with mouse monoclonal antibody R6A (which reacts with all normal erythrocytes, but fails to react with Rhnull erythrocytes) specifically precipitates the 34 000-mol.wt. component from normal erythrocytes. Similar studies with human anti-Rh(D) serum shows that this antibody reacts with the 32 000-mol.wt. component. The results suggest that the R6A-binding polypeptide and the Rh(D) polypeptide may be involved in the maintenance of the shape and viability of the human erythrocyte.

Chemical Precipitation↗
PubMed1983

The Wrb antigen, a receptor for Plasmodium falciparum malaria, is located on a helical region of the major membrane sialoglycoprotein of human red blood cells.

1. Immunoprecipitation of periodate/NaB3H4-labelled human erythrocytes using anti-Wrightb (Wrb) monoclonal antibodies showed that these antibodies specifically react with the major erythrocyte sialoglycoprotein alpha (glycophorin A). 2. Similar experiments on erythrocytes from the only known individual lacking the Wrb antigen but with otherwise normal sialoglycoproteins did not result in the immunoprecipitation of any sialoglycoprotein. 3. We suggest that the Wrb antigen is located on an alpha-helical region between residues 55 and 70 of sialoglycoprotein alpha.

Animals↗
PubMed1983

Erythrocyte membrane structure and function.

The structure and function of the proteins of the human erythrocyte membrane are discussed. The major integral proteins comprise the anion transport protein (band 3), the glucose transporter and four sialic acid-rich polypeptides. The anion transport protein equilibrates Cl- and HCO-3 between the plasma and red cell and also provides an anchorage site for peripheral proteins including those in the red cell cytoskeleton. The sialic acid-rich proteins are predominantly exposed at the surface of the cell. The bulk of the peripheral proteins are organized in a complex fashion to form a skeletal meshwork at the cytoplasmic surface of the membrane which maintains the shape and deformability of the red cell. The changes in membrane components during differentiation of the red cell are discussed.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1983

Incomplete glycosylation of erythrocyte membrane proteins in congenital dyserythropoietic anaemia type II (CDA II).

The alterations in the erythrocyte membrane proteins of individuals with congenital dyserythropoietic anaemia (CDA II) were studied. Alterations were observed in both the erythrocyte sialoglycoproteins and erythrocyte anion transport protein (Band 3). There was a decrease in the apparent molecular weight of the major sialoglycoprotein alpha (glycophorin A) as well as a general reduction in the intensity of staining of all the sialoglycoproteins by the PAS stain. Sialoglycoprotein alpha isolated from CDA II erythrocytes contained 30% less sialic acid than normal alpha. The anion transport protein of CDA II erythrocytes migrated as a band with a lower molecular weight than the normal protein on SDS-gel electrophoresis. The CDA II anion transport protein had a substantially reduced content of N-acetylglucosamine and galactose, which probably reflects a reduction in the number of N-acetyl-lactosamine units carried by the protein. Our results suggest that there is a general defect in glycosylation of the major membrane glycoproteins of CDA II erythrocytes. We suggest that this glycosylation defect is a consequence of bone marrow stress.

Anemia, Dyserythropoietic, Congenital↗
PubMed1982

Glycophorin as a possible receptor for Plasmodium falciparum.

Human red cells deficient in glycophorin B are partly resistant to invasion by Plasmodium falciparum and become completely resistant when glycophorin A is removed from their surface by trypsin treatment. Similar treatment of cells which have a hybrid glycophorin molecule renders them glycophorin-deficient and resistant to invasion. Tn and Wrb -ve cells with defined alterations in glycophorin A or B are also resistant to invasion. These findings suggest that both glycophorins A and B are involved in parasite invasion, indicate which parts of these molecules may be involved in this process, and provide the basis for a tentative model of parasite/red-cell interactions.

Blood Group Antigens↗
PubMed1982

Properties of N-maleoylmethionine sulphone, a novel impermeant maleimide, and its use in the selective labelling of the erythrocyte glucose-transport system.

1. The synthesis of N-maleoylmethionine sulphone (MMS), a membrane-impermeant protein-labelling reagent, is described. Radioactively labelled MMS can be readily prepared at high specific radioactivity from [35S]methionine. 2. The permeability of the erythrocyte membrane to the reagent was assessed by determining the extent of inactivation of glyceraldehyde 3-phosphate dehydrogenase after treatment of erythrocytes with MMS. Some inactivation of this enzyme was found when high concentrations (20mM) of the compound were used, but this could be prevented by pretreatment of the erythrocytes with 4,4'-di-isothiocyanatostilbene-2,2'-disulphonic acid, suggesting that MMS slowly enters the cells via the anion-transport system. 3. Treatment of erythrocytes with [35S]MMS resulted in the labelling of six major components. Labelling of erythrocyte membranes resulted in the intense labelling of many additional components. 4. MMS inhibited erythrocyte glucose transport. Cytochalasin b protected glucose transport against inactivation by MMS. Labelling experiments in erythrocytes in the presence and in the absence of cytochalasin b showed that the cytochalasin b-protected material was a broad band in the band-4.5 region.

Biological Transport↗
PubMed1981

Immunochemical evidence for hybrid sialoglycoproteins of human erythrocytes.

The two major sialoglycoproteins of the human erythrocyte membrane (alpha and delta, glycophorins A and B) have identical amino acid sequences for the first 26 residues from the amino terminus, except that alpha expresses M or N blood group antigen activity whereas deta carries only blood group N activity. In addition, the asparagine at position 26 on alpha carries an oligosaccharide chain which is absent from the same position on delta. The two sialoglycoproteins differ in their remaining amino acid sequence and delta expresses blood group Ss activity. There are also variant sialoglycoproteins which have properties of both the alpha and delta molecules and may be hybrids of these. Using antibodies directed against different structural regions of the major sialoglycoprotein alpha, we confirm here and two variant erythrocytes (Miltenberger class V (MiV) and Ph) contain hybrid sialoglycoprotein molecules (Fig. 1). These hybrid sialoglycoproteins arise from cross-over events between the genes coding for alpha and delta. It is suggested that the two genes are closely associated in the order alpha, delta (5' leads to 3') on the chromosome.

Amino Acid Sequence↗