Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An asymptomatic 26-year-old woman with mild macrocytic anemia (11.6 g Hb/dl) was studied. All biochemical parameters, bone marrow histology and cytogenetics were normal. The Ham's and sucrose tests were negative. A flow cytometric analysis revealed that CD55 and CD59 staining was absent in 20% and 21% of the granulocytes, but erythrocytes and CD34-positive bone marrow cells were CD55 and CD59 positive. Seven months after the initial study, the patient suffered an episode of hemoglobinuria, with mild anemia, moderate thrombocytopenia and a weak positive sucrose lysis test. A new flow cytometric analysis disclosed an increased percentage of CD55 and CD59 negative granulocytes and a 25% of erythrocytes with an intermediate pattern of fluorescence after CD59 labelling. At fourteen months, a population of CD55-deficient erythrocytes was detected and the Ham's test became positive. The present report is, to our knowledge, the first case of smoldering paroxysmal nocturnal hemoglobinuria in a patient with no previous aplastic anemia, or evident pancytopenia. The diagnosis was established by flow cytometry of peripheral blood granulocytes, with apparently phenotipically normal progenitor cells in an early stage of the disease. Flow cytometry appears to be a useful tool in our knowledge of paroxysmal nocturnal hemoglobinuria evolution.
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PMID:De novo smoldering paroxysmal nocturnal hemoglobinuria: a flow cytometric diagnosis. 958 88

Severe anemia is one of the most lethal complications in children infected with Plasmodium falciparum. The pathogenesis of this anemia is not completely understood. Experimental data from malaria-infected humans and animal models suggest that uninfected red cells have a shortened life span. This study looked for changes in the red cell surfaces of children with severe malarial anemia that could explain this accelerated destruction. A prospective case-control study was conducted of children with severe P falciparum anemia (hemoglobin of 5 g/dL or lower) admitted to a large general hospital in western Kenya. Children with severe anemia were compared with children who had symptoms of uncomplicated malaria and with asymptomatic children. Cytofluorometry was used to quantify in vitro erythrophagocytosis and to measure red cell surface immunoglobulin G (IgG) and the complement regulatory proteins CR1, CD55, and CD59. Red cells from patients with severe anemia were more susceptible to phagocytosis and also showed increased surface IgG and deficiencies in CR1 and CD55 compared with controls. Red cell surface CD59 was elevated in cases of severe anemia compared with asymptomatic controls but not as compared with symptomatic controls. The surface of red cells of children with severe P falciparum anemia is modified by the deposition of IgG and alterations in the levels of complement regulatory proteins. These changes could contribute to the accelerated destruction of red cells in these patients by mechanisms such as phagocytosis or complement-mediated lysis. (Blood. 2000;95:1481-1486)
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PMID:Red cell surface changes and erythrophagocytosis in children with severe plasmodium falciparum anemia. 1066 28

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by the deficiency of all proteins anchored to the membrane by the glycosyl-phosphatidylinositol (GPI) anchor. The receptor for urokinase-type plasminogen activator (uPAR) also is attached to the cell membrane by a GPI anchor, and that soluble uPAR (suPAR) is present in plasma. In the present study, we measured uPAR, CD55, and CD59 on granulocytes by means of flow cytometry and suPAR in plasma by means of immunoradiometric assay. The subjects were 20 patients with PNH, 59 other patients with anemia, and 21 healthy individuals. In patients with PNH, both the mean fluorescence intensity and the positive percentage of fluorescence-activated granulocytes of uPAR, CD55, and CD59 were remarkably decreased, whereas in patients with other forms of anemia, except 2 patients with aplastic anemia, the results were not altered in comparison with those for the healthy individuals. The level of uPAR was reduced to the same extent as were those of CD55 and CD59 on the PNH-affected granulocytes. Some peak shape abnormalities (double peaks, peak tailing, or both) in the histogram of fluorescence intensity were also found in patients with PNH. The suPAR concentration of PNH plasma was 4.04+/-2.47 ng/mL, which was higher than that of the healthy individuals, 1.73+/-0.96 ng/mL (P < .01). The positive percentage of fluorescence-activated granulocytes was inversely associated with the plasma suPAR level in patients with PNH (r = -0.79, P < .01). Our data suggest that measurement of uPAR on granulocytes by means of flow cytometry and of suPAR in plasma by means of immunoradiometric assay are specific techniques for the diagnosis of PNH.
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PMID:Diagnostic significance of measurement of the receptor for urokinase-type plasminogen activator on granulocytes and in plasma from patients with paroxysmal nocturnal hemoglobinuria. 1204 78

Severe malarial anaemia is a leading cause of death in African children younger than 3 years of age who are infected with Plasmodium falciparum. The pathogenesis of this anaemia is not understood. The purpose of this study was to determine if P. falciparum induces changes in RBC membranes that contribute to the immune destruction of RBCs. RBCs were collected from healthy subjects and tested using standard haemagglutination assays for 45 antigens representing 21 blood group systems/collections before and after exposure to P. falciparum, strain FVO. Lectins were used to determine whether crypt or neoantigens were expressed on the RBC membrane. Polybrene was used to detect changes in sialic acid. RBCs were cultured in vitro with and without the parasite, and blinded serologic studies were completed. CD35 (complement receptor 1), CD55 (decay-accelerating factor), CD59 (membrane inhibitor of reactive lysis) and CD47 (integrin-associated protein) flow cytometric assays were compared for infected and uninfected RBCs. The percentage of parasitaemia was determined using Giemsa-stained thin blood films. Two (Ch, Lub) of the 45 antigens had differing strengths of agglutination between infected and uninfected RBCs, but these differences were resolved with a second source of antisera. Forty-three antigens showed no significant differences in the strength of agglutination between the infected and uninfected RBCs. Lectin and polybrene testing showed no differences. CD35, CD55, CD59 and CD47 levels showed no significant differences. P. falciparum does not appear to alter the expression of classified immunogenic antigens on the RBC membrane in this in vitro system. The pathogenesis of the haemolytic episode that occurs in these children remains unclear.
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PMID:In vitro RBC exposure to Plasmodium falciparum has no effect on RBC antigen expression. 1207 78

Severe anemia is one of the most lethal complications of Plasmodium falciparum malaria. Red blood cells (RBCs) from children with severe malarial anemia are deficient in complement regulatory proteins (CR1 and CD55). A case-control, age- and sex-matched study was carried out to determine whether these deficiencies are acquired or inherited and the relative contribution of these complement regulatory protein deficiencies, the immune complex level, and the parasite density to the development of severe malarial anemia. RBC CR1 and CD55 deficiencies resolved after treatment, suggesting that these changes were acquired. Using conditional logistic regression, a decline in CD55 (or CR1) (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.1-8.1; P<.001) and an increase in immune complex level (OR, 2.6; 95% CI, 1.5-4.8; P=.001) were significantly associated with severe malarial anemia.
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PMID:Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. 1255 40

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder resulting from a somatic mutation in the hematopoietic stem cell. It is characterized by intravascular hemolysis, cytopenias, frequent infections, bone marrow hypoplasia, and a high incidence of life-threatening venous thrombosis. An absent glycosylphosphatidylinositol (GPI)-anchored receptor prevents several proteins from binding to the erythrocyte membrane. These include the complement-regulatory proteins, CD55 and CD59, whose absence results in enhanced complement-mediated lysis. Patients present with anemia and hemoglobinuria. Laboratory diagnosis includes the sucrose hemolysis test, Ham acid hemolysis test, and fluorescent-activated cell analysis. There is considerable overlap between PNH, aplastic anemia, and myelodysplastic syndrome and some cases evolve into acute leukemia. Treatment is mainly supportive consisting of transfusion therapy, anticoagulation, and antibiotic therapy. Hematopoietic stem cell transplantation may be curative.
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PMID:Paroxysmal nocturnal hemoglobinuria. 1531 92

Data from several laboratories suggest that erythrocyte complement-regulatory proteins, in particular complement receptor 1 (CR1), are important in the pathogenesis of severe malaria. Additional studies suggest that the levels of expression of CR1 and the complement regulator CD55 on erythrocytes vary with age, being low in young children and increasing with age. It is proposed that the interplay between the rate at which immunity develops during malaria exposure and the changes in levels of erythrocyte complement-regulatory proteins that occur with age might contribute to the differences in epidemiology of severe malaria-associated anaemia and cerebral malaria.
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PMID:Complement-regulatory proteins in severe malaria: too little or too much of a good thing? 1583 10

The mutation rate (mu) is a key biological feature of somatic cells that determines risk for malignant transformation, and it has been exceedingly difficult to measure in human cells. For this purpose, a potential sentinel is the X-linked PIG-A gene, because its inactivation causes lack of glycosylphosphatidylinositol-linked membrane proteins. We previously found that the frequency (f) of PIG-A mutant cells can be measured accurately by flow cytometry, even when f is very low. Here we measure both f and mu by culturing B-lymphoblastoid cell lines and first eliminating preexisting PIG-A mutants by flow sorting. After expansion in culture, the frequency of new mutants is determined by flow cytometry using antibodies specific for glycosylphosphatidylinositol-linked proteins (e.g., CD48, CD55, and CD59). The mutation rate is then calculated by the formula mu = f/d, where d is the number of cell divisions occurring in culture. The mean mu in cells from normal donors was 10.6 x 10(-7) mutations per cell division (range 2.4 to 29.6 x 10(-7)). The mean mu was elevated >30-fold in cells from patients with Fanconi anemia (P < 0.0001), and mu varied widely in ataxia-telangiectasia with a mean 4-fold elevation (P = 0.002). In contrast, mu was not significantly different from normal in cells from patients with Nijmegen breakage syndrome. Differences in mu could not be attributed to variations in plating efficiency. The mutation rate in man can now be measured routinely in B-lymphoblastoid cell lines, and it is elevated in cancer predisposition syndromes. This system should be useful in evaluating cancer risk and in the design of preventive strategies.
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PMID:A quantitative measurement of the human somatic mutation rate. 1616 84

Paroxysmal nocturnal hemoglobinuria (PNH) has been described in association separately with T cell large granular lymphocyte (LGL) clonal expansions and plasma cell dyscrasias. We describe a patient with anemia related to hemolytic PNH, with concurrent T cell LGL oligoclonal expansion and IgG lambda monoclonal gammopathy of undetermined significance. Peripheral blood flow cytometry revealed decreased expression of CD55 and CD59 on erythrocytes and decreased expression of CD55 and CD66 on neutrophils. An LGL population was present in the peripheral blood and was characterized as oligoclonal by polymerase chain reaction-based analysis of the T cell receptor gamma-chain variable region. Serum protein electrophoresis with immunofixation showed a low level IgG lambda monoclonal protein. We describe the diagnostic evaluation of this patient and provide a brief review of the reported associations among PNH, LGL clonal expansion, and monoclonal gammopathy.
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PMID:A patient with paroxysmal nocturnal hemoglobinuria, T cell large granular lymphocyte clonal expansion, and monoclonal gammopathy of undetermined significance. 1692 42

Hemolytic uremic syndrome is the clinical triad of thrombocytopenia, microangiopathic hemolytic anaemia and acute renal failure. Cases not associated with a preceding Shiga-like toxin producing Escherichia coli are described as atypical HUS (aHUS). Approximately 50% of patients with aHUS have mutations in one of three complement regulatory proteins, Factor H (CFH), membrane cofactor protein (MCP;CD46) or factor I (IF). A common feature of these three proteins is that they regulate complement by cofactor activity. Decay accelerating factor (DAF; CD55) regulates the complement system by disassociating the alternative and classical pathway convertases. Like CFH and MCP, the gene for DAF lies within the regulators of complement activation (RCA) gene cluster at 1q32. In 1998, we described linkage to this region in families with aHUS which led to the discovery of mutations in CFH and MCP. We therefore genotyped DAF in a panel of 46 aHUS patients including families with linkage to the RCA cluster. A mutation, I197V, was identified in one patient with familial HUS which was not found in 100 healthy controls. Molecular modelling of this mutation shows that the I197V mutation does not reside in an area which would be predicted to be important in decay accelerating activity. The expression of I197V on EBV-transformed B lymphocytes was equivalent to that of wild type controls. There was no significant decrease in decay acceleration activity of the recombinantly produced I197V mutant compared with wild type, as measured by a complement-mediated lytic assay. In conclusion, this study, identifies only one mutation in DAF in 46 patients with aHUS. This mutation, I197V, does not impair complement regulation and cannot be implicated in the pathogenesis of aHUS in this patient. This suggests that the complement regulatory abnormality in aHUS is principally one of deficient cofactor activity rather than of decay acceleration activity.
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PMID:The decay accelerating factor mutation I197V found in hemolytic uraemic syndrome does not impair complement regulation. 1736 71


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