Multiple cerebral infarctions were observed in a patient with refractory idiopathic thrombocytopenic purpura who was positive for lupus anticoagulant (LAC) when her platelet counts were 2000 microL-1. It is suspected that LAC may have played an important role in the pathogenesis of this patient's cerebral infarctions, although she had severe thrombocytopenia.
Red cell membrane proteins are composed of cytoskeletal proteins (spectrins, actin, and protein 4.1), integral proteins (band 3, and glycophorins), and anchoring proteins (ankyrin and protein 4.2). In disease states, abnormalities of α-spectrin, β-spectrin and protein 4.1 are now known as pathognomonic for hereditary elliptocytosis. The positions affected in these membrane protein genes were well correlated with the severity of the clinical findings and of the anomalies of their membrane ultrastructure and functions, as shown at best in three independent traits of β-spectrin anomalies; β-spectrin Lel'uy, β-spectrin Tokyo, and β-spectrin Nagoya. It should also be noted that the gene mutations of the C-terminal region of α-spectrin was strictly associated with hereditary elliptocytosis, contrary to the gene mutations all other regions, especially at the N-terminal region of α-spectrin which were associated with hereditary pherocytosis. In hereditary spherocytosis, which is most common in red cell membrane disorders, the gene mutations of ankyrin, band 3, and protein 4.2 were predominant. This disorder was found nearly exclusively in heterozygous states, rarely in homozygous states. It is also important to note that the incidence of the gene mutations pathognomonic for this disorder demonstrated great differences among various ethnic groups. The phenotypic characteristics of red cell membrane structure examined by electron microscopy demonstrated that total deficiency of band 3 proteins due to a homozygous nonsense mutation of the band 3 gene showed extremely unstable membrane ultrastructure, contrary to the total deficiency of protein 4.2 due to homozygous missense mutations with a moderate instability of the cytoskeletal network and the integral protein. Even in total deficiencies of protein 4.2, the phenotypic expressions were variable. Genotypic and phenotypic expressions in red cell membrane disorders are reviewed as based on the results from our laboratory for the recent 25 years.
Angiogenic factors are major causes of tumor progression in hematological malignancies, particularly multiple myeloma, as well as solid tumors. The introduction of thalidomide as an anti-angiogenic agent in myeloma treatment has demonstrated the importance of angiogenic factors in the progression of myeloma. However, the direct effects of angiogenic factors, particularly VEGFs, hypoxia, and thalidomide, on myeloma cells are not been documented. In this study, we demonstrate increased expression and production levels of VEGF in myeloma compared to non-myelomatous hematological lines, resistance to hypoxia and enhancement of VEGF-A production by hypoxia in myeloma, and direct growth inhibition of myeloma cells due to apoptosis and G1 arrest caused by TNFalpha upregulation induced by thalidomide. These findings may encourage the clinical use of anti-angiogenic agents for their cytostatic effects and the prevention of progression.
A 57-year-old man was admitted with severe anemia and hypergamma globulinemia. After a diagnosis of multiple myeloma and autoimmune hemolytic anemia was made, chemotherapy rapidly decreased the M-protein level and improved his anemia with normalization of the direct Coombs test. The immunoglobulin binding to the patient’s red cells was immunoglobulin G kappa chain like the myeloma M-protein. However, monoclonal immunoglobulin G derived from short-term culture of the patient’s bone marrow mononuclear cells did not bind to a panel of red cells. Therefore, the relationship between the M protein produced by his myeloma cells and hemolysis remained unclear.
Abstract Calcium (Ca) uptake was markedly increased in ATP‐depleted red cells of patients with iron deficiency anemia (IDA) compared to ATP‐depleted normal red cells. The extent of increased Ca uptake was related to the severity of iron deficiency as judged by decreased mean cell volume. Moreover, the increased Ca uptake returned to normal levels after oral iron supplementation therapy. The net calcium content of fresh red cells from iron‐deficient individuals was the same as in red cells from normal subjects. Sodium influx and ferric ion uptake appeared to be virtually unaffected in the iron deficient red cells.
