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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of myelodysplastic syndrome with haemolytic anaemia and a marked elliptocytosis is reported. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of erythrocyte membrane proteins revealed that the patient's band 4.1 was decreased to about 50-70% of that of control and contained abnormal molecule migrating in a faster mobility than normal band 4.1, which was confirmed by immunoblotting. The actin/spectrin ratio of the patient's ghosts diminished to about 70% of that of control ghosts. Flowcytometric analysis showed that the glycophorin C content of the patient's erythrocytes was reduced but maintained the level of about 70% of that of normal, indicating that the glycophorin C-band 4.1 interaction might not be so seriously damaged as to cause elliptocytic shape change. We postulate that the abnormal band 4.1 produced from the abnormal erythroid clone may be the primary molecular defect and result in a dysregulation of spectrin-actin interaction to cause erythrocyte shape change and membrane instability.
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PMID:Abnormal erythrocyte band 4.1 protein in myelodysplastic syndrome with elliptocytosis. 828 Jun 11

The erythrocyte membrane cytoskeletal protein 4.1 (4.1R) is a structural protein that confers stability and flexibility to erythrocytes via interactions with the cytoskeletal proteins spectrin and F-actin and with the band 3 and glycophorin C membrane proteins. Mutations in 4.1R can cause hereditary elliptocytosis, a disease characterized by a loss of the normal discoid morphology of erythrocytes, resulting in hemolytic anemia [1]. Different isoforms of the 4.1 protein have been identified in a wide variety of nonerythroid tissues by immunological methods [2-5]. The variation in molecular weight of these different 4.1 isoforms, which range from 30 to 210 kDa [6], has been attributed to complex alternative splicing of the 4.1R gene [7]. We recently identified two new 4.1 genes: one is generally expressed throughout the body (4. 1G) [8] and the other is expressed in central and peripheral neurons (4.1N) [9]. Here, we examined 4.1R expression by in situ hybridization analysis and found that 4.1R was selectively expressed in hematopoietic tissues and in specific neuronal populations. In the brain, high levels of 4.1R were discretely localized to granule cells in the cerebellum and dentate gyrus. We generated mice that lacked 4.1R expression; these mice had deficits in movement, coordination, balance and learning, in addition to the predicted hematological abnormalities. The neurobehavioral findings are consistent with the distribution of 4.1R in the brain, suggesting that 4.1R performs specific functions in the central nervous system.
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PMID:Neurobehavioral deficits in mice lacking the erythrocyte membrane cytoskeletal protein 4.1. 982 82

Five spontaneous, allelic mutations in the alpha-spectrin gene, Spna1, have been identified in mice (spherocytosis [sph], sph(1J), sph(2J), sph(2BC), sph(Dem)). All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals previously unknown consequences of red blood cell (RBC) spectrin deficiency. In sph(3J), a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice site resulting in premature termination of translation. In sph(Ihj), a premature stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly reduced RBC membrane spectrin content, decreased band 3, and absent beta-adducin. Reevaluation of available, previously described sph alleles reveals band 3 and adducin deficiency as well. In sph(4J), a missense mutation occurs in the C-terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia occurs despite minimally decreased membrane spectrin with normal band 3 levels and present, although reduced, beta-adducin. The severity of anemia in sph(4J) indicates that the highly conserved cysteine residue at the C-terminus of alpha-spectrin participates in interactions critical to membrane stability. The data reinforce the notion that a membrane bridge in addition to the classic protein 4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves interactions between spectrin, adducin, and band 3.
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PMID:Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in alpha-spectrin-deficient red cells. 2005 93