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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the most important factors for the proliferation and hemoglobin synthesis of erythroid cells is iron atom. This atom is tightly bound to serum transferrin (Tf) and is taken up by erythroblasts and reticulocytes through transferrin receptor (TfR). Both Tf and TfR are reutilizable and have roles for the efficient intracellular accumulation of iron. In addition to the reutilization (recycling), the expression of TfR is also regulated by cytoplasmic iron concentration; the increase of iron downregulate the synthesis of TfR at the translational level and vice versa. This mechanism was recently explained by the binding between "iron responsive element (IRE)" in the 5' end of TfR mRNA and IRE binding protein by a transacting manner. Johnstone et al, and we found that TfR was externalized from sheep reticulocyte and human erythroleukemia cell, K562, respectively. Furthermore, we confirmed that this shed TfR was detected in blood and concluded that the quantitation of TfR in serum is a useful index for evaluating the erythropoiesis. The serum TfR was increased in iron deficiency anemia, hemolytic anemia and polycythemia and was decreased in aplastic anemia. In renal anemia, it was increased after the administration of erythropoietin (Epo). By the in vitro liquid culture of peripheral blood stem cells using interleukin 3 and Epo, it was found that soluble TfR was derived from the erythroblasts during the maturation process.
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PMID:[Expression and extracellular release of transferrin receptors on erythropoiesis]. 189 Jul 32

Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA). The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied. Samples were collected before (baseline) and twice during the rhGM-CSF administration. The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period. The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased. Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation. The NK cell activity was suppressed (P less than .008) throughout the treatment. However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected. Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity. The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established.
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PMID:Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia. 220 31

Monoclonal antibody reagents were used to develop a sensitive enzyme-linked immunoassay for clinical measurement of circulating transferrin receptor. By using transferrin-bound receptor for the preparation of the immunologic reagents, we developed an assay that gives an identical dose-response curve with either free or transferrin-bound receptor. The mean concentration of circulating receptor in 82 normal male and female volunteers was 5.63 +/- 1.42 mg/L. The level was reduced significantly in patients with primary aplastic anemia and post-transplant aplasia (2.58 +/- 1.07 mg/L and 2.32 +/- 0.48 mg/L, respectively) and was sharply elevated in patients with hemolytic anemia and iron deficiency anemia (33.1 +/- 17 and 18.0 +/- 11.4 mg/L, respectively). Our assay values are approximately 20-fold higher than results published previously in a study that used an immunoradiometric assay. The disparity apparently relates to a difference in sensitivity of the latter assay for free and transferrin-bound receptor. Measurements of serum transferrin receptor provide a useful clinical index of either total or iron-deficiency erythropoiesis.
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PMID:The clinical measurement of serum transferrin receptor. 267 98

Macrophages (MAC) are important effector cells of the immune system but also play an essential role as regulatory cells in hematopoiesis. They originate from circulating monocytes (MO) as immature precursor cells that undergo terminal differentiation upon migration from the capillary bed into the various tissues. In the presence of serum, MAC maturation from blood MO is observed in vitro and can be followed by the expression of maturation-associated antigens (MAX.1, .3, .11, and .26; transferrin receptor, 13C2, CD16). We have tested blood MO from 22 patients with aplastic anemia (AA) for their capacity to undergo terminal maturation in vitro. After isolation, blood MO in six patients expressed CD14 molecules at low density when compared to normals. On culture for 7 days, in 15 patients various abnormalities could be shown by phenotype analysis using cell-enzyme-linked immunosorbent assay (ELISA) and an immunoperoxidase staining technique of single cells. Abnormalities ranged from the distinctive failure of mature MAC to express single surface antigens (eg, gp64-MAX.1) to complete inhibition of the development of a MAC maturation-associated phenotype. In three patients the maturational defect was found to persist in complete remission after successful therapy with antileukocyte globulin (ALG). Neither in other immunosuppressed or multiple-transfused patients nor in those with bone marrow hypoplasia secondary to cancer chemotherapy and during hematologic reconstitution following autologous bone marrow transplantation (BMT), defective MO maturation in vitro was seen. Our data provide evidence for the existence of serious disorders within the MO-MAC lineage in patients with AA. This observation may either reflect the stem-cell defect or indicate a MAC involvement in the pathogenesis of the disease.
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PMID:Defective monocyte-to-macrophage maturation in patients with aplastic anemia. 280 53

Serum transferrin receptors were measured by a sandwich radioimmunoassay procedure in patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia. The mean circulating transferrin receptor concentration of normal subjects and patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia are 253 +/- 82 ng/mL, 730 +/- 391 ng/mL, 1,426 +/- 1,079 ng/mL, and 182 +/- 39 ng/mL, respectively. The values for those with iron deficiency anemia and autoimmune hemolytic anemia were significantly higher than that of normal controls and the values for those with aplastic anemia were lower than that of normal controls. After iron supplementation in iron deficiency anemia, the serum transferrin receptor values increased twofold over those of pretreatment values. This increase parallels an increase in peripheral reticulocytes. Therefore, the number of circulating transferrin receptors in anemic patients may reflect the level of bone marrow erythropoiesis and is a potentially useful new index for red cell production.
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PMID:Serum transferrin receptor as a new index of erythropoiesis. 367 19

Serum erythropoietin (EPO) and soluble transferrin receptor levels were serially measured in 74 patients with aplastic anaemia (AA). As control groups we investigated healthy controls (n = 24) and patients with iron-deficiency (n = 23) or haemolytic anaemia (n = 16). There was a significant negative correlation of log EPO on haematocrit both in AA patients and in the anaemic control group. However, for the same degree of anaemia, log EPO levels in AA were significantly higher than in iron-deficiency or haemolytic anaemia. EPO levels at diagnosis did not correlate with severity of aplastic anaemia, nor did they predict outcome after immunosuppression. During immunosuppressive treatment of AA with anti-thymocyte globulin and cyclosporine A, EPO levels were significantly lower compared with pre-treatment values without a corresponding change in haematocrit. This impaired EPO response to anaemia during immunosuppression might affect recovery of erythropoiesis. In AA patients, EPO levels declined with haemopoietic recovery. However, compared with normal controls, EPO levels in remission patients were still higher with respect to their haematocrit. Results of this study argue against the model of a simple feedback regulation of EPO via hypoxic anaemia. Our data support the hypothesis that cytokines and the erythropoietic progenitor pool are involved in the regulation of EPO production. The results illustrate that serial measurements of EPO along with therapeutic interventions are necessary to identify patients who might benefit from treatment with exogenous recombinant human EPO.
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PMID:Serum erythropoietin and serum transferrin receptor levels in aplastic anaemia. 780 72

To characterize the persistent abnormalities of hematopoiesis in aplastic anemia (AA) after immunosuppression with antilymphocyte globulin (ALG), we analyzed the quantity, phenotype, and growth properties of hematopoietic progenitor cells in 13 patients who received ALG treatment. Flow cytometry (FACS) revealed a deficiency of CD34+ cells in bone marrow (BM) of all patients. This deficiency was most severe (40-fold) in 4 patients in AA relapse. In 9 patients in remission, CD34+ cells were reduced 2-10-fold and showed no correlation with the ALG-induced improvement of peripheral blood cell counts. The proportion of CD34+ cells carrying c-kit receptors was abnormally low (2-10-fold below normal) in 5 of 13 AA patients. These patients also displayed low levels of c-kit mRNA by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the CD34+ cell population was almost completely depleted of CD34+CD38- early hematopoietic progenitors in all AA patients. The proportion of CD34+ cells expressing lineage differentiation antigens CD33, CD71, and CD45RA in AA was increased, as compared to control BM. Formation of hematopoietic colonies by FACS-purified CD34+ cells was nearly absent in 4 relapsed patients, normal in 4 of 9, and decreased (up to 10-fold) in 5 of 9 patients in remission. The degree of impairment of colony-forming ability by AA progenitors correlated well with the reduction of CD34+ c-kit+ cells. The best proliferative response of CD34+ cells was observed in the presence of stem cell factor and, in some cases, fit3 ligand. Our results indicate that the disease process in AA depletes immature BM progenitors, thus providing a plausible explanation for persistent defects in colony-forming ability and long-term regenerative capacity of AA marrow after immunosuppression. Analysis of the immunophenotypes and the proliferative properties of purified progenitors may be useful for estimating degree of hematopoietic recovery in ALG-treated patients.
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PMID:Deficiency of CD34+ c-kit+ and CD34+38- hematopoietic precursors in aplastic anemia after immunosuppressive treatment. 870 44

The human placenta transferrin receptor was purified in the form of transferrin-transferrin receptor complex (Tf-TfR), and a monospecific polyclonal antibody against TfR was developed by a Tf-coupled Sepharose 4B affinity chromatography to remove the anti-Tf components in the antiserum. A sandwich enzyme-linked immunoabsorbent assay (ELISA) was established for measuring serum transferrin receptor (sTfR) by using monoclonal antibody OKT9 and monospecific polyclonal antibody. This method is simple, specific and sensitive and has a good accuracy. The measurement of sTfR showed that the level of normal children was 4.54 +/- 1.08 mg/L. There were increased levels of sTfR in patients with severe iron deficiency anemia and those with hemolytic anemia (13.92 +/- 4.45 mg/L and 9.94 +/- 3.22 mg/L, respectively). In patients with aplastic anemia, the level was decreased (2.06 +/- 0.82 mg/L). These results indicate that the sTfR measurement has a differential significance for diagnoses of various anemia.
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PMID:[The sandwich enzyme-linked immunoabsorbent assay of serum transferrin receptor by using monoclonal and polyclonal antibodies]. 873 60

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (> 1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia.
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PMID:Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes. 946 42

Chloramphenicol is an antibiotic that consistently suppresses the bone marrow and induces sideroblastic anemia. It is also a rare cause of aplastic anemia. These toxicities are thought to be related to mitochondrial dysfunction, since chloramphenicol inhibits mitochondrial protein synthesis. We hypothesized that chloramphenicol-induced mitochondrial impairment alters the synthesis of ferritin and the transferrin receptor. After treating K562 erythroleukemia cells with a therapeutic dose of chloramphenicol (10 microg/ml) for 4 days, there was a marked decrease in cell surface transferrin receptor expression and de novo ferritin synthesis associated with significant decreases in cytochrome c oxidase activity, ATP levels, respiratory activity, and cell growth. Decreases in the transferrin receptor and ferritin were associated with reduced and unchanged message levels, respectively. The mechanism by which mitochondrial dysfunction alters these important proteins in iron homeostasis is not clear. A global decrease in synthetic processes seems unlikely, since the expression of the cellular adhesion proteins VLA4 and CD58 was not significantly decreased by chloramphenicol, nor were the message levels of beta-actin or ferritin. The alterations were not accompanied by changes in binding of the iron response protein (IRP) to the iron-responsive element (IRE), although cytosolic aconitase activity was reduced by 27% in chloramphenicol-treated cells. A disturbance in iron homeostasis due to alterations in the transferrin receptor and ferritin may explain the hypochromic-microcytic anemia and the accumulation of nonferritin iron in the mitochondria in some individuals after chloramphenicol therapy. Also, these studies provide evidence of a link between mitochondrial impairment and iron metabolism in K562 cells.
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PMID:Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions. 1043 Jan 73


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