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Biomedical subjects

M E Reid

Publications and source records attributed to M E Reid.

At least 145 records · Page 8Linked to original sources
PubMed1995

A novel common Kell antigen, TOU, and its spatial relationship to other Kell antigens.

A 47-year-old native American (TOU) was admitted to hospital for hip surgery. His serum agglutinated all red blood cells (RBCs) tested except Ko and DTT-treated RBCs and was weakly reactive with RBCs known to have a weak expression of Kell antigens, namely Kmod, McLeod, Kp(a+b-) (KEL:3,-4) and K:-13 (KEL:-13) phenotypes. RBCs from three siblings, a son and a daughter were incompatible with TOU's antibody. TOU's RBCs had the common Kell phenotype: K-k+Kp(a-b+c-)Ku+Js(a-b+)Ul(a-)K:11,-17K:14,-24K:12,13,18,19, 22,-23(KEL:-1,2,-3,4,5,-6,7,-10,11,12,13,14,-17,18,19,-21,22,-23,-24). Since TOU's RBCs were not agglutinated by an unidentified Kell-related antibody (IAN), tests were performed to show that TOU and IAN were mutually compatible. IAN is a Latino female hospitalised for a hysterectomy. The TOU antigen was shown to be located on the Kell glycoprotein by a monoclonal antibody immobilisation of erythrocyte antigen (MAIEA) assay. The unique pattern of reactivity obtained with TOU and IAN antibodies using this assay indicated the TOU epitope to be in an area remote from other Kell antigens, namely K, k, Kpa, Kpb, Kpc, Ku, Jsa, Jsb, U1a, K11, K12, K13, K14, Wka, K18, K19, K22 and K24 (KEL1, KEL2, KEL3, KEL4, KEL5, KEL6, KEL7, KEL11, KEL12, KEL13, KEL14, KEL17, KEL18, KEL4, KEL5, KEL6, KEL7, KEL11, KEL12, KEL13, KEL14, KEL17, KEL18, KEL19, KEL21, KEL22 and KEL24) but close to the low-incidence antigen K23 (KEL23).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1995

K12 is located on the Kell blood group protein in proximity to K/k and Jsa/Jsb.

K12 is a high-prevalence antigen, with no known antithetical partner, that is associated with the Kell blood group system. We report studies on the 5th propositus (MS) with the K:-12 phenotype and the second case to show that the K12 is inherited. The anti-K12 in his serum did not destroy antigen-positive incompatible red cells transfused on at least 3 occasions over 6 years. Red cell membranes from MS possessed the Kell protein that was indistinguishable from control membranes. K12 antigen was shown by immunoprecipitation to be on a protein with an apparent molecular mass of 93,000 and by monoclonal antibody immobilization of erythrocyte antigens (MAIEA) assay to be on the Kell protein in proximity to K/k and Jsa/Jsb antigens. These data remove the K:-12 phenotype from its current Kell-related (or para Kell) status and elevates the K12 antigen to a bona fide member of the Kell blood group system.

Antibodies, Monoclonal↗
PubMed1995

Expression of the erythrocyte antigen Henshaw (He; MNS6): serological and immunochemical studies.

Production of murine monoclonal antibodies to the low prevalence MNS antigen Henshaw (He; MNS6) has enabled more detailed study of this antigen. Using these directly hemagglutinating anti-He, red blood cells (RBCs) from 1695 people of African origin were screened in the USA and England. The prevalence of He+ samples among these donors was 2.1%. In Natal, blood samples from 1218 black donors were screened with rabbit anti-He. The prevalence of He+ donors in this population was 7.0%. Immunoblotting confirmed that the He antigen is carried on an erythrocyte membrane component with a molecular mass that is indistinguishable from glycophorin B. Hemagglutination and immunoblotting demonstrated that ten of 56 He+ samples tested more extensively had a reduced expression of the He antigen. The majority of He+ RBCs were S+; those He+ RBC samples that were S-s+ more frequently had a weakened expression of He.

Antibodies, Monoclonal↗
PubMed1995

LISS-dependent autoantibody with apparent anti-U specificity.

Nonspecific binding of gamma globulin and complement, resulting in falsely positive indirect antiglobulin tests, has occurred with use of low-ionic strength saline solution (LISS) reagents. These LISS-dependent antibodies have not been described in association with any particular disease state, nor do they have any apparent clinical significance. We present a LISS-dependent antibody with apparent autoanti-U specificity.

Journal Article↗
PubMed1994

Molecular basis of reduced or absent expression of decay-accelerating factor in Cromer blood group phenotypes.

The human erythrocyte blood group system Cromer consists of high-incidence and low-incidence antigens that reside on decay-accelerating factor (DAF; CD55), a glycosyl-phosphatidylinositol-anchored membrane protein that regulates complement activation on cell surfaces. In the Cromer phenotypes Dr(a-) and Inab there is reduced or absent expression of DAF, respectively. This study investigated the molecular basis of the reduced DAF expression by polymerase chain reaction amplification of genomic DNA and RNA/cDNA obtained from Epstein-Barr virus-transformed lymphoblastoid cell lines. Sequence analysis of the Inab propositus showed a single nucleotide substitution in exon 2 of the DAF gene and at the corresponding position in the cDNA, G314-->A resulting in Trp53-->Stop. This truncation near the amino terminus explains the complete absence of surface DAF in the Inab phenotype. A similar analysis was performed for two Dr(a-) individuals, including KZ, who was previously reported to be Inab phenotype but is now shown by immunochemical and serologic methods to be Dr(a-) phenotype. A single nucleotide change was found in exon 5 of the DAF gene, C649-->T resulting in Ser165-->Leu, which we had previously shown to lead to loss of the Dra epitope. However, two species of cDNA were found, one encoding full-length DAF with the single amino acid change and the more abundant species having a 44-nucleotide deletion. The 44 nucleotide deletion includes the single polymorphic site, which creates a cryptic branch point in the Dr(a-) allele that leads to use of a downstream cryptic acceptor splice site. This shifts the reading frame and leads to a premature stop codon that precludes membrane anchoring. Thus, the single point mutation in the Dr(a-) phenotype results in a novel use of alternative splicing and provides a molecular explanation for both the antigenicity and the reduced DAF expression seen in this phenotype.

Amino Acid Sequence↗
PubMed1994

Remodeling of the transmembrane segment in human glycophorin by aberrant RNA splicing.

This paper describes the identification in S-s-U-erythrocytes of a novel glycophorin (GP), He(P2), with structural variations in both its extracellular and transmembrane domains. In the exon II-intron 2 region, a sequence transfer from GPA to GPB, probably via the mechanism of gene conversion, was associated with the induction of multiple untemplated nucleotide replacements. These changes defined the sequence for the He epitope while concomitantly abolishing GPB-associated N antigenicity. Moreover, the GPHe(P2) gene carries two splice site mutations that coordinately affect the processing of exon V coding for the transmembrane segment. The C-->G transversion at the 3' end of exon V created a cryptic acceptor splice site, whereas the G-->T transversion at the +5 position of intron 5 altered the consensus of the donor splice site. Transcript sequencing revealed that neither site was utilized in the splicing of GPHe(P2) pre-mRNA. Rather, complete skipping of exon V and subsequent joining of exon IV to exon VI caused a shift in the open reading frame, which remodeled GPHe(P2) with an elongated new hydrophobic sequence for membrane anchoring. As a result, GPHe(P2) does not display the S and U epitopes although it still contains an intact linear sequence for the two antigens. These findings illustrate how exon and intron sequences concertedly determine the specificity of in vivo splice site selection. In addition, they pinpoint the conformational dependence of the S, s, and U antigens and the importance of the hinge region for their presentation.

Amino Acid Sequence↗
PubMed1994

Localization of the protein 4.1-binding site on human erythrocyte glycophorins C and D.

The flexibility of the human erythrocyte membrane is mediated by an underlying network of skeletal proteins which interact with the membrane through ankyrin and protein 4.1. The nature of the membrane attachment site(s) for protein 4.1 has yet to be fully elucidated. In this paper we show that purified protein 4.1 binds much less strongly to alkali-stripped membranes from erythrocytes of individuals with total glycophorin C and D deficiency (Leach phenotype) than to alkali-stripped normal membranes. We further show that a synthetic peptide corresponding to amino acid residues 82-98 of the cytoplasmic domain of glycophorin C specifically binds to purified protein 4.1 and inhibits protein 4.1 binding to alkali-stripped normal membranes. The same synthetic peptide binds directly to membranes from individuals with glycophorin C and D deficiency but not to normal membranes. These results indicate that glycophorins C and D provide major membrane attachment sites for protein 4.1 in normal erythrocytes and that this interaction is mediated by protein 4.1 binding to amino acid residues 82-98 of glycophorin C and 61-77 of glycophorin D.

Amino Acid Sequence↗
PubMed1994

A family of McLeod syndrome, masquerading as chorea-acanthocytosis.

A man, aged 52, is reported to show (1) adult onset, (2) progressive orofacial dyskinesia and choreic movements of the extremities, (3) tongue biting, (4) denervation of the peripheral nerves, (5) acanthocytosis, and (6) increased serum creatine kinase, which are characteristic of chorea-acanthocytosis. The Kell blood group examination on erythrocytes disclosed that the propositus had McLeod phenotype, and his mother and one of his sisters were carriers of the McLeod phenotype. Thus, he was diagnosed as having McLeod syndrome. A criterion of exclusion of McLeod phenotype on erythrocytes should be added to the diagnostic criteria of chorea-acanthocytosis. Moreover, chronic neurogenic changes instead of myogenic changes were electromyographically and histopathologically verified in the muscle.

Acanthocytes↗
PubMed1994

Sulindac-induced immune hemolytic anemia.

BACKGROUND: Sulindac, a nonsteroidal, anti-inflammatory, indene-derived drug, caused life-threatening immune hemolytic anemia in an individual with back pain. CASE REPORT: A patient was admitted to the hospital with immune hemolytic anemia and kidney and liver failure after several days ingestion of sulindac. The direct antiglobulin test was positive with polyspecific and monospecific anti-IgG but not with anti-C3. The eluate did not react in routine tests but reacted strongly after the addition of sulindac. The serum contained a sulindac-dependent antibody reacting to a titer of 32. The sulindac-dependent antibody was of both IgG and IgM classes and had no apparent blood group specificity. The antibody agglutinated red cells from humans and chimpanzees but not from chickens, rabbits, or sheep, which implied that a specific component on human and chimpanzee red cells was needed for reactivity. The antibody reacted with red cells treated with trypsin, papain, pronase, dithiothreitol, and sialidase. With aggressive medical care, the patient's condition improved. CONCLUSION: These findings appear compatible with the so-called immune complex mechanism for drug-induced immune hemolytic anemia. Physicians are alerted to the severe nature of this syndrome.

Aged↗
PubMed1994

Evaluation of monoclonal anti-glycophorin B as an unusual anti-S.

BACKGROUND: Monoclonal antibody 148 is a murine monoclonal anti-glycophorin B that preferentially reacts with S+ human red cells. STUDY DESIGN AND METHODS: Serologic and immunochemical studies were performed using red cells with various phenotypes. RESULTS: These studies reveal that this monoclonal antibody is unusual in that it fails to agglutinate S+ TSEN+ red cells and agglutinates S- St(a+) and S- Dantu+ red cells. CONCLUSION: These results allow the prediction of the glycophorin composition of GP.Hop (Mi.IV) red cells.

Amino Acid Sequence↗
PubMed1994

Transient loss of proteins carrying Kell and Lutheran red cell antigens during consecutive relapses of autoimmune thrombocytopenia.

A patient is described in whom two consecutive relapses of autoimmune thrombocytopenic purpura (AITP) were associated with loss of red cell antigens of the Kell and Lutheran blood group systems respectively. During the second relapse the glycoprotein CD44 and to a lesser extent the LW antigen were also depressed. Both relapses were associated with concomitant production of IgG antibody recognizing high-frequency determinants on the corresponding antigen-carrying protein. Blocking of antigen sites by these antibodies was not the cause of reduced antigen expression, because immunoblotting studies showed absence of Kell protein during the first relapse, and Lutheran protein during the second. On both occasions the red cell changes reverted to normal with disappearance of the antibody as the AITP entered remission. There was no evidence of clonal lymphocyte expansion as demonstrated using immunoglobulin JH and T cell receptor beta chain probes.

Adult↗
PubMed1994

Some concepts relating to the molecular genetic basis of certain MNS blood group antigens.

The unfolding story of genes encoding variant glycophorin molecules is already known to be more complicated than described here. The principles outlined provide a basis for understanding the fundamental events that occur in genes encoding the glycophorins as well as genes encoding unrelated proteins carrying other blood group antigens. Over 20 different genes involving the GYPA and GYPB family have been described. These genes arise from gene rearrangements within a relatively short region. This hot spot of activity has inverted palindromic sequences, which are known to be sites for DNA recombination. Similar structures exist in the major histocompatibility complex (MHC) where allelic diversity is a functional requisite. However, the significance of allelic diversity in the glycophorin gene family is not understood. The GYPA, GYPB and GYPE gene cluster is known to be prone to mutation by radiation because there is a high incidence of somatic mutation events in atomic bomb survivors, in people exposed to accidental radiation, in patients with Bloom's syndrome and in patients receiving radiation therapy. The mutation events were dose dependent: the greater the exposure, the greater proportion of red blood cells exhibited mutations. While it is known that MHC diversity protects against infection, the reason for glycophorin rearrangements remains to be determined.

Amino Acid Sequence↗
PubMed1994

Molecular basis of glycophorin C variants and their associated blood group antigens.

The normal and variant forms of GPC and GPD molecules carry antigens of the Gerbich blood group system. This blood group system comprises three high-incidence antigens (Ge2, Ge3 and Ge4) and four low-incidence antigens (Wb, Lsa, Dha and Ana). Erythrocytes of the Ge and Yus phenotypes lack normal GPC and GPD molecules but express variant molecules (denoted GPC.Ge, GPC.Yus, respectively) that functionally substitute for normal GPC and GPD in the membrane. Leach phenotype cells lack GPC and GPD molecules and are elliptocytic in shape with a membrane that is less deformable than that of normal cells. The Lsa antigen is expressed on higher molecular-weight variants of GPC (GPC.Lsa) and GPD (GPD.Lsa). Wb, Dha and Ana antigens arise from point mutations in the GYPC gene and are expressed on GPC.Wb, GPC.Dha and GPD.Ana, respectively. The structure of each of the variant GPC and GPD molecules and the location of the Gerbich blood group system antigens is discussed. The GYPC gene, located on chromosome 2q14-q21, is 13.5 kb long and comprises four exons. Exons 1, 2 and most of exon 3 encode the N-terminal extracellular domain while the remainder of exon 3 and exon 4 encode transmembrane and cytoplasmic domains of GPC. Exons 2 and 3 are highly homologous, with less than 5% nucleotide divergence. The molecular basis of generation of variation GPC and GPD molecules, and the structure of the GYPC gene from different Leach phenotype individuals, is discussed.

Amino Acid Sequence↗
PubMed1994

A novel variant of the human blood group K1 antigen.

A discrepancy in duplicate anti-K1 typing in a parentage case led to the discovery of an unusual K1 blood group antigen. Red blood cells from the propositus (JC) express a rare variant of the K1 antigen that is detectable by only 8 of 72 sera containing anti-K1. Absorption and elution studies using reactive anti-K1 confirmed the presence of a K1 antigen. Nonreactive anti-K1 was not absorbed by or eluted from JC's red blood cells. Red cells from 3 of the propositus's siblings also had the variant K1 antigen. The variant antigen exhibited qualitative as well as quantitative differences as compared to normal K1, and we have named it K1var.

Adult↗
PubMed1994

Evidence for expression of the Joa blood group antigen on the Gya/Hy-active glycoprotein.

The phenotypic association between the non-assigned high-incidence antigen Joa and the Gya collection antigens Gya and Hy was investigated by haemagglutination studies, flow cytometric analysis, immune precipitation and immunoblotting experiments. In haemagglutination tests anti-Joa gave the same pattern of reactivity with erythrocytes pre-treated with pronase, trypsin, alpha-chymotrypsin and thiol reducing agents as did anti-Gya and anti-Hy. In addition, similar to that found for anti-Gya and anti-Hy, anti Joa also showed reduced binding, as determined by haemagglutination and flow cytometric analysis, to erythrocytes from patients with paroxysmal nocturnal haemoglobinuria. Immune precipitates prepared from radio-iodinated antigen-positive red cells with anti-Joa, anti-Gya and anti-Hy gave similar results--a major component of M(r) 49,000-60,000 (the Gya/Hy-active glycoprotein) and a second component of M(r) 85,000-92,000 (this may be a dimer of the Gya/Hy-active glycoprotein, or a coprecipitated protein). These immune precipitates, when probed with both anti-Gya and anti-Hy under non-reducing conditions, gave a positive immunoblotting reaction to both the M(r) 49,000-60,000 and the M(r) 85,000-92,000 components. These results strongly suggest that the Joa antigen is expressed on the same glycoprotein that carries the Gya and Hy antigens.

Blood Group Antigens↗
PubMed1993

Membrane attachment sites for the membrane cytoskeletal protein 4.1 of the red blood cell.

The identity of the membrane binding sites for the membrane cytoskeletal protein 4.1 of the human red blood cell has been investigated. Exhaustive proteolysis of the membrane with a range of proteases led to the elimination of only some 60% of all binding sites. The predominant integral membrane protein, band 3, as well as glycophorin A, was totally digested at levels of proteolysis that were essentially without effect on the number of 4.1 binding sites. Proteolysis caused scission of the polypeptide chain of glycophorin C (together with the minor product, glycophorin D, of the same gene), but left a fragment from the region of the C-terminus still attached to the membrane. We have found a low-molecular weight protein, possessing an epitope (recognized by an antibody directed against the cytoplasmic domain of glycophorin C) in common with this proteolytic fragment, in cells of a Leach phenotype, which are characterized by lack of extracellular epitopes of glycophorin C. When these membranes were extracted at low ionic strength to dissociate the membrane cytoskeleton, approximately half the content of 4.1 was liberated, compared with only some 25% from normal membranes. Cells of a different variant of the Leach phenotype, which are totally devoid of glycophorin C, lost close to 70% of their 4.1 under these circumstances. The Rh(D) transmembrane protein, which interacts with the membrane cytoskeleton, is also resistant to proteolysis of the cytoplasmic membrane surface, but Rhnull cells, devoid of this protein, showed no decreased retention of 4.1. The results suggest that glycophorin C (with D) may contain two types of binding site for 4.1, which would be sufficient in number to account for all the strong binding of 4.1 on normal membranes; modulation of binding at one of the sites by another protein or by lipid is not excluded. A possible site for reinitiation of translation overlapping the premature stop codon in the mutant expressing the truncated glycophorin C can be discerned.

Binding Sites↗
PubMed1993

Exon skipping caused by DNA recombination that introduces a defective donor splice site into the human glycophorin A gene.

We report here the pre-mRNA splicing of the human glycophorin Mz (HGpMz) gene altered by a defective donor splice site introduced into the third intron via the mechanism of gene conversion. We found that the directional transfer from HGpB(delta) to HGpA(alpha) of a 145-base pair silent homologous segment had resulted in HGpMz as an alpha-beta-alpha hybrid gene with a G-T transversion in the consensus GT motif of the 5'-donor splice site. Transcript analysis showed the presence in the Mz reticulocytes of three major glycophorin cDNA species of which two occurred as the shortened and aberrantly spliced products of HGpMz pre-mRNA lacking the sequences encoded by one and two exons, respectively. The skipping of exon III results in one HGpMz protein with 99 amino acids that bears the M and Sta blood group antigens, whereas the coincident skipping of both exon III and exon IV leads to the expression of a minor HGpMz protein with 86 amino acids. These results indicate that the translocated defective donor splice site not only causes uniform skipping of the upstream exon but also affects the processing of the downstream exon. Complementing our previous studies, the finding that the active and inactive splice sites can be transposed by DNA recombination and alternatively used to construct new glycophorin alleles reveals a novel mechanism for sequence diversification in human genes.

Amino Acid Sequence↗