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

The normal response to anemic or hypoxic hypoxia is synthesis and release of erythropoietin in accord with the concept that erythropoietin production is controlled by a renal oxygen sensor. In this study, erythropoietin production, as predicted, was abrogated in patients with renal impairment (55 cases), but normal in nonuremic individuals. Specifically, patients with rheumatoid arthritis (34 cases), sickle cell anemia (25 cases), aregenerative anemia (27 cases), and aplastic anemia (13 cases) had erythropoietin titers overlapping with those observed in simple anemia (61 cases) at corresponding hematocrits. The response of polycythemic laboratory animals to hypoxia is more difficult to fit within the concept of an oxygen sensor responsive both to anemic and hypoxic hypoxia. If the polycythemia was induced by hypertransfusion, erythropoietin production in response to hypoxia was, as predicted, less than that observed in normal animals. If, however the polycythemia was induced by previous exposure to hypoxia, the animals responded to hypoxia as though they were not polycythemic. An explanation for this challenging observation may provide a clue as to the operation of the oxygen sensor.
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PMID:Erythropoietin titers in response to anemia or hypoxia. 366 51

The study of induction of Friend erythroleukemic cell lines during the last decade has enriched our understanding of late erythroid differentiation. In comparison, little information is available on early erythroid differentiation. We describe here the isolation and characterization of a highly inducible clone from a murine erythroid cell line, which is capable of forming colonies that possess properties of the early erythroid burst progenitor. We found that a combination of erythropoietin (Epo), spleen conditioned medium (SCM), and plasma from a patient with aplastic anemia (Apa) induces over 95% of cells from this clone (clone 12) to form colonies with the properties of burst or mixed burst blast-like colonies. Examination of the culture conditions of these cells indicated that alpha medium was more efficient for colony induction than Iscove's medium, and that the addition of two-mercaptoethanol did not improve the induction process. These factors (EPo, SCM, and Apa) must be present for 4 days in order for induction to take place. It is hoped that the isolation of this highly inducible cell clone will enrich our understanding of early erythroid differentiation.
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PMID:Isolation and characterization of an erythroid cell line highly inducible to form erythroid burst-like colonies. 372 72

Untreated human serum is known to be toxic to in vitro assays for erythropoietin, including the mouse spleen cell assay system (MSCA). This phenomenon had previously been shown to be mediated by complement-dependent IgM heteroantibodies and can be overcome by heating the serum at 56 degrees C for 30 minutes. Using the MSCA, we have found that the toxic effect of serum could also be removed by treatment with a precipitating antibody against the C3c component of complement. The effects of the two methods of complement inactivation on the measurement of stimulatory activity in serum have been compared. For normal serum, the results after heat inactivation and antibody treatment were similar. In contrast, serum from a patient with aplastic anemia gave a result equivalent to 327 mU erythropoietin/ml after heat treatment, but after antibody treatment equivalent to 1,520 mU erythropoietin/ml. Gel permeation chromatography of unheated, heated, and antibody-treated sera showed that heating markedly reduced the activity of the erythropoietin peak. Seventy percent of the activity of partially purified urinary erythropoietin was lost during heating in the presence of normal serum. In addition, heating caused the appearance of high molecular weight compounds that are stimulatory in the MSCA. The level of this activity appeared to be directly related to the stimulatory activity of the unheated serum.
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PMID:In vitro bioassay of erythropoietic activity in serum using mouse spleen cells. The effect of heat inactivation on serum erythropoietin. 374 58

Serum erythropoietic activity was determined in 32 patients with beta thalassemia major and intermedia. Quantitation was performed by an in vitro bioassay using rabbit erythroid precursor cells (CFU-E) either by colony assay or by 3H-thymidine uptake. 20 polytransfused beta-thalassemic major patients had erythropoietic activity (mean 89.3 +/- 36 milliunits/ml) which was not significantly different (p greater than 0.2) from normal individuals (51.3 +/- 32 milliunits/ml). 12 untransfused patients with beta thalassemia intermedia were found to have comparable serum erythropoietic activity (p greater than 0.01). These levels were much lower than those found in patients with aplastic anemia who had a comparable degree of anemia. We have shown that the low EPO activity in thalassemic patients was not due to experimental conditions (excess of ferritin, low transferrin) nor to specific inhibitors appearing in this disease. No correlation was found between the erythropoietic activity and sex or other clinical parameters of the patients such as severity of the anemia, splenectomy, iron chelation or transfusion therapy. 4 young thalassemic children (1-2 yr of age) studied had high erythropoietic activity ranging from 661 to 5793 milliunits/ml--significantly different from normal children of the same age. It is suggested, therefore, that a decrease in serum erythropoietin levels develops during the course of the disease.
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PMID:Erythropoietin activity in the serum of beta thalassemic patients. 378 74

Methylcellulose culture assay was used to detect committed haemopoietic stem cells, CFU-C and CFU-E, in aplastic anaemia patients with autologous haemopoietic reconstitution. Severe diminution of CFU-C was found in all the patients studied and the absence of a dose-response to colony stimulating factor (CSF) was demonstrated. A reduced number of CFU-E and lower erythropoietin (Ep) sensitivity of those progenitors was detected as well. Autologous serum added to the bone marrow cultures of these patients enhanced the growth of CFU-C but inhibited CFU-E growth. According to the results presented, some residual damage at the stem cell level is suggested.
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PMID:Myelopoiesis and erythropoiesis of bone marrow cells cultured in vitro in patients recovered from aplastic anaemia. 387 77

Burst-promoting activity (BPA) in the sera of patients with various types of anemia and polycythemia was compared with that of normal subjects by an in vitro method using mouse bone marrow cells. The control culture contained normal human AB serum instead of sample materials. Results were expressed as a percentage of burst numbers in control cultures. Serum erythropoietin (Epo) levels were determined by a radioimmunoassay. Serum BPA in patients with aplastic anemia (155.4 +/- 56.7%, mean +/- SD) was significantly higher than that in normal subjects (112.1 +/- 29.1%, Wilcoxon's rank sum test, P less than 0.05). However, serum BPA in patients with uremic anemia (122.2 +/- 26.5%), polycythemia vera (101.9 +/- 19.5%) and stress polycythemia (115.5 +/- 25.6%) was not significantly different from normal subjects. There was a correlation between serum BPA and Epo titers in patients with aplastic anemia and paroxysmal nocturnal hemoglobinuria (r = 0.81, t test, P less than 0.001).
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PMID:Burst-promoting activity in anemia and polycythemia. 395 12

We have analysed the contribution to megakaryocyte colony formation in methylcellulose made by human plasma, serum, media conditioned by phytohemagglutinin (PHA) stimulated leukocytes (PHA-LCM), erythropoietin (EPO) preparations, and platelets. The culture system was used as a bioassay for megakaryocyte colony stimulating activity (Meg-CSA) in plasma samples of patients with perturbed megakaryocytopoiesis. Preparations of heparinized platelet-poor plasma yielded the most consistent results. Platelet-poor plasma of normal subjects will at best facilitate the occasional growth of small megakaryocyte colonies. Colony frequency and size are reproducibly enhanced in the presence of PHA-LCM as a source of exogenous Meg-CSA. Commercially available EPO preparations may vary in their content of activities that influence megakaryocyte colony formation. Addition of these preparations to cultures that contain plasma and PHA-LCM usually does not enhance colony formation. In contrast to platelet-poor plasma, platelet rich plasma and serum are less supportive of megakaryocyte colony growth. It is suggested that this loss of activity may be related to the release of inhibitors by activated platelets or alternatively caused by absorption of activities by platelets. Plasma samples from patients with megakaryocytopoietic dysfunction may contain components that promote colony formation without addition of PHA-LCM or EPO. This phenomenon is consistently observed for patients with severe aplastic anemia and bone marrow transplant recipients after completion of their ablative preparative regimen.
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PMID:Characterization of human megakaryocytic colony formation in human plasma. 404 52

The activity capable of promoting the growth of human erythroid burst-forming cells (BFU-E) in culture was measured in the sera from 39 patients with aplastic anemia (AA) and compared with similar activity in patients with various other hematologic disorders and 31 normal subjects. Burst-promoting activity (BPA) was determined by its ability to support erythroid burst growth from adherent cell-depleted normal human marrow cells. The results were expressed as the percentage of burst growth supported by test serum compared with cultures established in the presence of 20% test serum and 2.5% phytohemagglutinin-stimulated lymphocyte conditioned medium. The mean BPA level in normal serum was 18.5% (1.5 +/- SEM) and was not significantly different from BPA levels in patients with various forms of nonhypoplastic anemia or polycythemia (10.2% +/- 1.2%). In contrast, 15 of the 39 patients with AA had elevated BPA levels, ranging from 40.0% to 106.0%. These elevated levels did not correlate with serum erythropoietin or hematocrit values, white blood cell count, platelet count, time from diagnosis, or the presence or numbers of BFU-E in circulation. The BPA was shown not to be T cell growth factor (interleukin-2), and the effect was not blocked by the addition of cyclosporine to culture, consistent with a direct effect of this activity on BFU-E. When the 39 patients with AA were treated with antithymocyte globulin, 20 obtained a complete or partial remission. BPA levels determined from sera obtained before treatment did not correlate with response or duration of survival but did correlate with granulocyte-macrophage colony-stimulating activity (GM-CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors in human serum. erythroid burst-promoting activity in normal subjects and in patients with severe aplastic anemia. 404 96

A number of studies have demonstrated that certain immunocompetent cells play a role in the regulation of normal erythropoiesis. These regulatory cells (monocytes--macrophages, lymphocytes) modulate almost every phase of the erythropoietic process, and along with erythropoietin represent the major controlling force in erythropoiesis. Evidence indicate that pathological alterations of these cell-mediated activities can lead to clinical disturbances of red cell production such as is seen in patients with Diamond-Blackfan syndrome and aplastic anemia.
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PMID:Role of cell--cell interaction in normal and abnormal erythropoiesis. 644 59

Significant in vivo stimulation of granulopoiesis was induced in mice by the administration of an extract from the urine of patients with aplastic anemia (AA). Sialic acid has been identified as an important molecular component for the in vivo biological activity of this granulopoietic factor, "granulopoietin," which is distinct and different from endotoxin. Urine from patients with AA was successively fractionated by Sephadex G-50 and DEAE-cellulose chromatography. The resultant extract, which we refer to as AA urinary extract, contained approximately equal to 44 international units of erythropoietin per A unit of protein and induced 15,000 colonies of granulocyte/macrophage precursor cells (granulocyte/macrophage colony-forming units, CFU-gm) per A unit of protein with mouse bone marrow. Eight daily intraperitoneal injections of this extract in mice induced a 6.2-fold increase in peripheral blood granulocytes and a 14.6-fold increase of splenic CFU-gm, with concomitant increases in the proliferation rates of CFU-gm in both bone marrow and spleen. Pretreatment of the AA urinary extract with sialidase significantly diminished these granulopoietic effects in vivo (P less than 0.001). In contrast, both extracts (i.e., native AA and sialidase-treated AA urinary extracts) revealed high granulocyte/macrophage colony-stimulating factor activity in vitro when clonal assays were performed with mouse bone marrow. Increased in vivo and in vitro granulopoietic activities were found in the concanavalin A "break-through" fraction, indicating that these activities were due to protein(s) that did not bind to the lectin. These results reveal that this urinary extract from patients with AA is capable of inducing significant granulopoiesis in mice and that sialic acid is an important component in the maintenance of this granulopoietic effect in vivo but not in vitro.
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PMID:In vivo stimulation of murine granulopoiesis by human urinary extract from patients with aplastic anemia. 657 18


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