Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied three glycosylphosphatidylinositol (GPI) linked proteins on the erythrocytes of 14 patients with paroxysmal nocturnal haemoglobinuria (PNH). The pattern observed was bimodal in 12 of the patients and trimodal in two. Ten patients had a red cell population with normal CD59 antigen (membrane inhibitor of reactive lysis, MIRL), decay accelerating factor (DAF or CD55) and lymphocyte function-associated antigen (LFA-3 or CD58) and a second abnormal PNH population with absent CD59 antigen, DAF and LFA-3. The other two patients with a bimodal pattern had a red cell population with normal CD59 antigen, DAF and LFA-3 and an abnormal population with reduced, but not absent, CD59 antigen and DAF. The LFA-3 on the abnormal red cells in these two patients appeared to be only slightly reduced. The two patients with a trimodal pattern had a normal population, a population with reduced, not absent, CD59 antigen and DAF, and a population with complete absence of CD59 antigen, DAF and LFA-3. The accuracy of the Ham test in estimating the proportion of red cells with the PNH defect in the two types of PNH was assessed. The case of one patient who appeared to be 'rescued' from severe aplastic anaemia by the development of PNH is described.
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PMID:Two distinct patterns of glycosylphosphatidylinositol (GPI) linked protein deficiency in the red cells of patients with paroxysmal nocturnal haemoglobinuria. 137 29

The phosphatidylinositol (PI) bound proteins (acetylcholin-esterase (ACE), decay accelerating factor (DAF), leucocyte function antigen type 3 (LFA-3) and Fc-receptor type III (FcRIII] were estimated by flow cytometry on blood cells from four patients with paroxysmal nocturnal haemoglobinuria (PNH), nine patients with 'non-PNH' haemolytic anaemia, four patients with aplastic anaemia and a reference group of 15 healthy individuals to assess the applicability of flow cytometric measurements in the clinical mapping of the PNH defect. Estimation of DAF on granulocytes or monocytes offered the highest diagnostic sensitivity and specificity and may constitute an easy screening method for the PNH defect. One PNH patient had a negative Ham's test at the time of study and normal or near normal levels of PI-bound proteins on erythrocytes, but reduced expression of DAF and FcRIII on granulocytes and DAF on monocytes. The analytical and biological coefficient of variation for flow cytometric estimation of PI-bound proteins was in the range of 4.8-13% and 12-24%, respectively. Blood samples should be analysed without delay, since storage produced spuriously high results. The results were expressed as molecules per cell after calibration with commercially available standards and validated by comparison with previously reported results obtained by other methods. It is proposed that this way of reporting flow cytometric results should be generally adopted to facilitate comparison of results between laboratories.
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PMID:Estimation of PI-bound proteins on blood cells from PNH patients by quantitative flow cytometry. 169 48

We used X-chromosome methylation patterns to study clonality in aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). AA is usually not considered to be a clonal stem cell disorder, although this has not been directly investigated. PNH is generally assumed to be a clonal disorder, although there is contradictory evidence. Methylation analysis was performed on DNA from separated granulocytes and mononuclear cells, using the M27 beta and hypoxanthine phosphoribosyl transferase (HPRT) probes. Six of seven AA patients showed a polyclonal pattern of X inactivation. In contrast, five of five PNH patients showed a monoclonal pattern. These results imply that at least 80% of the cell population derives from a single stem cell. Because this high proportion of PNH cells might be considered surprising, three patients were studied for membrane expression of decay accelerating factor (DAF). In support of the DNA data, more than 95% of the granulocytes were DAF--ve in all three cases. We conclude that AA is predominantly a polyclonal disorder, whereas PNH is a clonal stem cell disorder. Our data support a model in which a single PNH stem cell has a growth advantage over other remaining stem cells and eventually dominates hematopoiesis.
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PMID:Acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria: studies on clonality. 163 35

Scleroderma and aplastic anaemia (AA) occurred simultaneously in a patient. Treatment with antilymphocyte globulin (ALG) resulted in some improvement of the scleroderma and a partial, temporary response of the AA. Both the scleroderma and AA then responded dramatically to cyclosporin (CSA) therapy. Subsequently, a positive Ham's test, together with a reduction in the phosphatidyl-inositolglycan (PIG) anchored membrane proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), confirmed a diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) affecting erythroid, myeloid and lymphoid cell lineages. We hypothesize that the pathogenesis of the bone marrow failure in this patient was a stem cell defect with a secondary immune response involving T-lymphocytes that may have simultaneously triggered the pancytopenia and scleroderma.
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PMID:Response of aplastic anaemia and scleroderma to cyclosporin. 791 56

The review outlines developments in research on paroxysmal nocturnal haemoglobinuria (PNH). The disease is due to a somatic mutation of the PIG-A gene. This results in deficiency of the protein, GPI (glucosyl phosphatidyl inositol), which serves as an anchor for several membrane-bound proteins including MIRL (CD59; membrane inhibitor of reactive lysis) and DAF (CD55; decay accelerating factor). The absence of these proteins results in increased cellular sensitivity to complement-mediated lysis, affecting not only red cells, leukocytes and platelets, but also haemopoietic stem cells. This explains the often complex clinical picture in PNH (haemolysis, pancytopenia and increased thrombotic predisposition), and the well known relationship between PNH and aplastic anaemia.
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PMID:[PNH--paroxysmal nocturnal hemoglobinuria. An old disease explained by new technology]. 942 27

The peripheral blood cells of ten patients with biopsy-proven aplastic anemia were studied by means of flow-cytometry in order to assess the expression of two phosphatidylinositol-anchored surface proteins: CD55/DAF (decay accelerating factor) and CD59/MIRL (membrane inhibitor of reactive lysis). An abnormal expression was found in five of these ten patients, whereas the "traditional" tests for paroxysmal nocturnal hemoglobinuria (PNH) were positive only on two of these five individuals. Five of the aplastic patients were treated with anti-thymocyte globulin and cyclosporin-A and three entered a complete remission; of the latter, one had CD55/CD59 deficiencies whereas two did not. Along the study period one patient with a hemolytic pattern of PNH was identified. It is concluded that CD55 and/or CD59 abnormalities are frequent in Mexican mestizo patients with aplastic anemia, that the aplastic presentation of PNH is more frequent in Mexico than the hemolytic presentation, that the flow-cytometric identification of CPI-anchored proteins is more sensitive than the "traditional" PNH tests, and that some patients with PNH-aplasia may respond to intensive immunosuppressive treatment. The flow-cytometric identification of GPI-anchored cell surface proteins should replace the "traditional" tests in the identification of patients with PNH.
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PMID:[Glycosilphosphatidylinositol-anchored cell surface protein deficiency in Mexican mestizo patients with aplastic anemia]. 1034 61

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder in which intravascular hemolysis results from the somatic mutation of the totipotent stem cells causing an intrinsic defect in red cell membrane. PNH cells lack glycosylphosphatidylinositol (GPI) anchored membrane proteins. Of these proteins absence of CD 59 (MIRL--membrane inhibitor of reactive lysis, protectin) and CD 55 (DAF--decay accelerating factor) makes the PNH cells abnormally sensitive to the lytic action of complement. The defect appears to be in the somatic mutation of the X-linked PIG-A (phosphatidylinositolglycan A class) gene which participate in an early step of GPI-anchor synthesis. PNH is characterized by recurrent life threatening venous thromboses and an intimate association with aplastic anemia (AA). It seems that PNH always coexists with bone marrow failure (BMF) (37). The possible explanation may be that some GPI-anchored proteins may be a critical target recognized by immune effector cells. PNH clones not possessing these critical GPI-anchored proteins will survive because they are selectively resistant to the autoimmune assault that eliminates most normal clones. The flow cytometry of erythrocytes using anti-CD 59 and anti-CD 59 and anti-CD 55 of granulocytes has been now introduced as a very sensitive and quantitative method of PNH diagnosis able to detect PNH cells even in normal individuals (1,54). Thus it seems now clear that we must make distinction between the detection of very occasional PNH cells in patients with BMF and PNH as a clinicohematological entity. Unfortunately, we do not know the minimal content of PNH cells required to produce clinical signs of PNH (38).
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PMID:Paroxysmal nocturnal hemoglobinuria (membrane defect, pathogenesis, aplastic anemia, diagnosis). 1093 78