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At least 19 recordsLinked to original sources

PubMed1975

Intestinal iron absorption under the influence of available storage iron and erythroblastic hyperplasia. Comparative studies in children with hereditary spherocytosis, nonspherocytic enzymopenic hemolytic anemia, acquired hemolytic anemia, vitamin B12 deficiency induced megaloblastic anemia, erythroblastic hypoplasia and aplastic anemia.

A high negative correlation (coefficient similar to 0.9) between increased 59Fe absorption from a diagnostic 0.56 mg 59Fe2+ dose and the depletion of available storage iron was observed in menstruating and pregnant women, fullterm and premature infants, blood donors, patients with infections, inflammations, tumors, hepatic cirrhosis, gastric surgery, increased urogenital or gastrointestinal blood loss. The increased diagnostic 59Fe2+ absorption is a reliable and sensitive indicator of at least depleted iron stores or prelatent iron deficiency as caused by iron malnutrition or maldigestion, increased iron requirement in pregnancy, infancy, urogenital or gastrointestinal blood loss. Although the messenger system which signalyzes the depletion of iron stores to the iron absorbing enterocytes of the duodenal and jejunal mucosa is not yet known available storage iron seems to control intestinal iron absorption under normal and the great majority o pathological condition in humans. Anemia per se or high erythropoietin levels in blood do not influence iron absorption since patients with even severe erythroblastic hypoplasia, aplastic anemia and megaloblastic anemia due to vitamin B12 deficiency absorb iron according to their iron stores. An only mild hyperplasia of the erythropoietic system in the bone marrow does also not effect iron absorption which was still under the control of available storage iron in patients with hereditary spherocytosis, nonspherocytic congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency, acquired hemolytic anemia and vitamin B12 deficiency induced megaloblastic anemia..

Adolescent↗

PubMed1979

[In vitro study of erythroblast precursors in Vasquez disease (polycythemia vera). Arguments in favor of a double population of erythroblastic stem cells in the bone marrow].

In vitro studies using the plasma clot culture system have been performed in order to compare the red cell pregenitors able to rise to erythrocytic colonies in 7 days (CFUE) in the bone marrow of polycythemia vera (PV), secondary polycythemias and normal subjects. In PV but never in normal individuals or secondary polycythemias, the bone marrow cells producing erythroid colonies without addition of erythropoietin were found. The erythropoietin dode response curves in PV is biphasic with a plateau up to a concentration of erythropoietin of 0.02-0.05 i.U./ml followed by a near normal response to erythropoietin at higher doses. Thus our results demonstrate that two populations of erythroid stem cells coexist in PV, one being abnormally sensitive to (or independant of) erythropoietin, the other normally responding to erythropoietin. After remission induced by P32 treatment, the abnormal population can disappear but the prognostic significance of this disappearance is uncertain. On the whole these results are in agreement with those of others laboratories using the plasma clot culture system. The reasons of the disagreement with the data published using the methylcellulose technic of culture are discussed.

Animals↗

PubMed1978

Quantitative ultrastructural characterisation of rabbit erythroblasts and of 3H uridine incorporation into their nuclear components.

Electron microscopic-autoradiographic and morphometric investigations were carried out in erythroblasts from rabbit bone marrow. 1. to obtain quantitative data for the erythroblast classes. 2. to determine quantitative-morphometrically the incorporation rate of 3H uridine into the cell components of the different erythroblast classes. 3. to evaluate the influence of UV irradiation on the incorporation of 3H uridine. According to ultrastructural criteria erythroblasts are divided into 3 classes: basophilic erythroblasts (BE), polychromatic erythroblasts (PE) and orthochromatic erythroblasts (OE). The areas of the 3 classes of erythroblasts are in a ratio of 1:0.5:0.43. In all classes the portion of the nucleus is between 56 and 58.8%. The portion of mitochondria decreases from 13.3% (BE) to 9.3% (PE), and to 6.3% (OE) respectively. Simultaneously the portion of heterochromatin in the nuclear area rises from 24.2% (BE) to 49.8% (PE), and to 63.2% (OE) whereas the percentage of euchromatin decreased correspondingly. Nucleoli were found only in 78% of the BE and in 3.4% of the PE. For the quantitative determination of the silver grains and silver filaments, respectively, the morphometric procedures have been adapted to the particular conditions. So it was necessary to estimate the areas covered by silver grains of filaments. The silver grains or filaments localised in the nuclear area are in the range from 84.6 to 93.4%. The percentage of silver grains of the total cellular area is 14.4% in BE, 6.8% in PE and 4% in OE. In a similar way the relative values of the nucleolus (total) and the euchromatin and heterochromatin are reduced. UV irradiation of bone marrow in vitro for 10 to 20 min does not cause any significant changes in the incorporation of 3H uridine. This result is in contrast to other published experiments on the influence of UV on the RNA synthesis. It is assumed that the irradiation dose was too low to induce a measurable effect on the RNA synthesis or the point of investigation was too early.

Animals↗

PubMed1979

delta-Aminolevulinic acid synthetase in erythroblasts of patients with pyridoxine-responsive anemia. Hypercatabolism caused by the increased susceptibility to the controlling protease.

Properties of delta-aminolevulinic acid synthetase in erythroblasts of patients with pyridoxine-responsive anemia were investigated with special reference to the protease in mitochondria of erythroblasts. delta-Aminolevulinic acid synthetase activity in erythroblasts of patients with this disease before treatment was extremely decreased, whereas it gradually increased in parallel with the improvement of anemia by the therapy with pyridoxal phosphate. The amount of apo-delta-aminolevulinic acid synthetase in erythroblasts before treatment was also extremely diminished. Apparent affinity to pyridoxal phosphate of the apo-delta-aminolevulinic acid synthetase obtained from erythroblasts of the patients was almost the same as that of normal controls. The activity of a new protease which is considered to be engaged in the regulation of delta-aminolevulinic acid synthetase levels in mitochondria of erythroblasts was shown to be in normal range in erythroblasts of the patients. On the other hand, apo-delta-aminolevulinic acid synthetase obtained from the patients was extremely sensitive to the protease. These results indicate that disturbance of heme synthesis characteristic to pyridoxine-responsive anemia could be ascribed to the hypercatabolism of delta-aminolevulinic acid synthetase caused by the increased susceptibility to the controlling protease in erythroblasts.

5-Aminolevulinate Synthetase↗

PubMed1975

Erythroblastic islands and ineffective erythropoiesis in acute myeloid leukaemia.

The erythropoietic part of the bone marrow has been morphologically analysed in 34 untreated, anaemic patients with acute myeloid leukaemia and in 17 healthy controls. In the patients with leukaemia the percentage of basophilic erythroblasts was abnormally high and elevated mitotic indices of the erythroblasts were recorded. The accumulation of basophilic erythroblasts and a high frequency of megaloblastoid changes of the cells may indicate ineffective erythropoiesis. A threefold increase of "erythroblastic islands", i.e. erythroblasts in contact with reticulum cells were recorded in the patients with erythroleukaemia and a twofold increase in the patients with acute myeloid leukaemia. The erythroblastic islands may indicate phagocytosis of defective erythroblasts and an intramedullary haemolysis may thus contribute to the development of anaemia.

Adolescent↗

PubMedDate not supplied

[Comparative investigation of the non-histone proteins of chromatin from pigeon erythroblasts and erythrocytes].

Chromosomal non-histone proteins are obtained from nuclei of two types of pigeon erythroid cells: erythroblasts (cells active in RNA synthesis) and erythrocytes (cells with repressed RNA synthesis). They are well soluble in solutions of low ionic strength. Electrophoretic separation of the obtained non-histone proteins in polyacrylamide gels with urea and SDS shows the presence of qualitative differences in the pattern of non-histone proteins of chromatine from erythroblasts and erythrocytes. By electrophoresis in urea some protein bands of non-histone proteins of chromatine from erythroblasts were found which disappear with the aging of cells. At the same time two protein fractions were observed in chromatine from erythrocytes which were absent in that of erythroblasts. Disappearance of some high molecular weight protein fractions from erythrocyte chromatine as compared to erythroblasts was observed by separation of the non-histone proteins in the presence of SDS. These fractions of the non-histone proteins disappearing during aging of cells are well extractable from erythroblast chromatine by 0.35 M NaCl solution. In the in vitro system with E. coli RNA polymerase addition of non-histone proteins of chromatine from erythroblasts to chromatine from erythrocytes increases RNA synthesis 2--3 times. At the same time addition of non-histone proteins from erythrocytes is either without any influence on this process or somewhat inhibiting.

Animals↗

PubMed1975

Nucleolar changes in maturing avian erythroblasts and erythrocytes.

Maturing erythroblasts and erythrocytes were studied in chickens and adult hens to provide more information on the presence and frequency of various nucleolar types in these cells. Nucleoli were present at all stages of erythroblastic and erythrocytic development except in the case of a few reticulocytes and the mature erythrocytes. The number of nucleoli per cell (expressed as the nucleolar coefficient) reached a maximum at the stage of the polychromatic erythroblast. Early erythroblasts were characterized by the presence of compact nucleoli or nucleoli with nucleolonemata. Rings shaped nucleoli and micronucleoli increased in number with further maturation. Cells of the final erythroblast stage (orthochromatic erythroblasts) contained mostly micronucleoli, and micronucleoli alone were present in reticulocytes and mature erythrocytes.

Animals↗

PubMed1992

Transcriptional repression of band 3 and CAII in v-erbA transformed erythroblasts accounts for an important part of the leukaemic phenotype.

The v-erbA oncogene confers two prominent properties on transformed erythroblasts: a block of spontaneous differentiation and tolerance to wide variations in the pH or ionic strength of culture medium. V-erbA acts as a constitutive repressor of erythrocyte-specific gene transcription, arresting the expression of at least three different erythroid genes: the erythrocyte anion transporter (band 3), carbonic anhydrase II (CAII) and delta-aminolevulinate synthase (ALA-S). To test whether or not the v-erbA induced repression of these genes is causally related to the v-erbA induced leukaemic phenotype, we have reintroduced the genes for band 3 or CAII into transformed erythroblasts via retrovirus vectors. We show here that such erythroblasts, expressing v-erbA, require the same narrow range of medium pH and ion concentration for growth as do transformed erythroblasts lacking v-erbA, i.e. the v-erbA induced tolerance to pH variation was abrogated. The v-erbA induced differentiation block, however, remained unaffected by the re-expression of band 3 and was only slightly affected by the re-expression of CAII. Our experiments show that the two v-erbA-related 'erythroblast transformation parameters' are separable: suppression of band 3 and CAII accounts for one parameter (pH/ion tolerance), while the second parameter (differentiation block) must involve v-erbA regulation of a different set of target genes.

5-Aminolevulinate Synthetase↗

PubMed1977

Erythroblastic transformation of chronic granulocytic leukemia.

Erythroblastic transformation of chronic granulocytic leukemia was found in seven of 67 unselected patients with blast crisis. This morphologic picture of erythroblastic transformation was indistinguishable from that in erythroleukemia or Di Guglielmo's syndrome. The median survival of the patients with erythroblastic transformation was two months, considerably less than the four-month median survival in the entire series of 67 patients. Only two brief partial remissions were obtained with combination chemotherapy. The causes of death were primarily hemorrhage and infection, related to thrombocytopenia and neutropenia. In this regard, the patients with erythroblastic transformation resembled all the patients with blast crisis and patients with acute leukemia in general. The erythroblastic transformation seems to represent a morphologic variant of chronic granulocytic leukemia blast crisis, without apparent prognostic or therapeutic implications.

Adult↗

PubMed1979

Some aspects of the biology of multinucleate and giant mononucleate erythroblasts in a patient with CDA, type III.

Marrow cells of a patient with CDA, type III, were (1) incubated with 3H-thymidine for 0.5 h and studied using a combination of Feulgen microspectrophotometry and light microscope autoradiography and (2) incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. The data revealed multiple abnormalities in the proliferation of erythroblasts but no abnormality in the distribution of neutrophil promyelocytes and myelocytes in the different stages of interphase. Some mononucleate erythroblasts had DNA contents of 4-20c and the multinucleate erythroblasts had total DNA contents of 2-40c. In about 40% of the multinucleate erythroblasts, only some of the nuclei within the same cell incorporated 3H-thymidine and the electron microscope autoradiographic studies revealed that the nuclei which failed to synthesize DNA virtually always showed abnormalities in the electron-density of the heterochromatin or euchromatin or a Swiss-cheese appearance of the heterochromatin. Furthermore, in some multinucleate cells but not in others, the ultrastructurally abnormal nuclei showed a marked depression of RNA synthesis when compared with the normal-looking nuclei within the same cell. An occasional binucleate, multinucleate and giant mononucleate erythroblast showed ultrastructural changes suggestive of advanced degeneration and such cells, which showed a marked depression of RNA and protein synthesis, appeared to be phagocytosed by macrophages.

Anemia↗

PubMed1992

Asynchronous synthesis of membrane skeletal proteins during terminal maturation of murine erythroblasts.

To study the changes in the synthesis of the major membrane skeletal proteins, their assembly on the membrane, and their turnover during terminal red blood cell maturation in vivo, we have compared early proerythroblasts and late erythroblasts obtained from the spleens of mice at different times after infection with the anemia-inducing strain of Friend virus (FVA). Metabolic labeling of these cells indicates striking differences between early and late erythroblasts. In early erythroblasts, spectrin and ankyrin are synthesized in large amounts in the cytosol with proportionately high levels of spectrin and ankyrin messenger RNA (mRNA). In contrast, only small amounts of these polypeptides are incorporated into the skeleton, which is markedly unstable. In late erythroblasts, however, the synthesis of spectrin and ankyrin and their mRNA levels are substantially reduced, yet the net amounts of these polypeptides assembled in the membrane skeleton are markedly increased, and the membrane skeleton becomes stable with no detectable protein turnover. The mRNA levels and the synthesis of the band 3 and 4.1 proteins are increased considerably in terminally differentiated normoblasts with a concomitant increase in the net amount and the half-life of the newly assembled spectrin and ankyrin. Thus, the increased accumulation of spectrin and ankyrin at the late erythroblast stage is a consequence of an increased recruitment of these proteins on the membrane and an increase in their stability rather than a transcriptional upregulation. This is in contrast to band 3 and 4.1 proteins, which accumulate in direct proportion to their mRNA levels and rates of synthesis. These results suggest a key role for the band 3 and 4.1 proteins in conferring a long-term stability to the membrane skeleton during terminal red blood cell differentiation.

Anemia↗

PubMed1978

Erythroblast kinetics in pernicious anaemia, erythroleukaemia and sideroblastic anaemia.

DNA synthesis time (Ts) and 3H-thymidine labelling index (TLI) of erythroblasts have been determined in 25 patients with various types of haematologic disorders using in vitro double labelling method. No remarkable differences in both Ts and TLI were noted between haematologically normal subjects and patients with increased effective erythropoiesis (haemolytic anaemias), suggesting that the cell cycle time is not principally altered under the augmented erythropoiesis. In pernicious anaemia, Ts of basophilic erythroblasts was significantly shortened and TLI was elevated above normal. Normalization of erythropoiesis by vitamin B12 was associated with a transient increase of TLI in polychromatic erythroblasts, which was interpreted to reflect prevention of intramedullary premature death of basophilic megaloblasts. Erythroleukaemia showed a markedly prolonged Ts and lowered TLI indicating the presence of cells with prolonged cell cycle time. These findings contrasted to that of pernicious anaemia despite certain morphological as well as functional similarities. In idiopathic sideroblastic anaemia, prolongation of Ts was observed to a similar extent as erythroleukaemia, while TLI remained almost normal. In 2 cases with suspected erythroleukaemia presenting an intermediate clinical picture between erythroleukaemia and sideroblastic anaemia, Ts of basophilic erythroblasts was found to be prolonged along with modestly lowered TLI.

Anemia, Pernicious↗

PubMed1978

Progenitor cells of erythroblasts: an in vitro investigation of erythropoietin-responsive cells of guinea pig bone marrow.

The experiments were designed to test whether or not erythroblast progenitor cell function could be demonstrated in a morphological cell type designated as "transitional cells." Two cell fractions, were obtained from the bone marrow of normal and polycythemic guinea pigs. One fraction (F1) was enriched in transitional cells and contained few, if any, other cell types which could be considered as candidates for erythropoietin responsive cells (ERC). The other fraction (F2) contained undifferentiated blast cells as well as transitional cells. The effect of human urinary erythropoiesis stimulating factors (ESF) on heme synthesis was compared in these two fractions by measuring 59Fe incorporation into heme. ESF was more effective in stimulating heme synthesis in guinea pig bone marrow cells than homologous sera obtained from anemic or hypoxic animals. The majority of ERC sedimented in F2, but the stimulation index was comparable in the two fractions. It was confirmed by radioautography that the ESF response in F1 was due to the generation of proerythroblasts and basophilic erythroblasts that incorporated 55Fe. The generation of these cells in F1 was dependent on the addition of ESF to the cultures, whereas 55Fe-labeled erythroblasts were recovered from cultured of F2 not supplemented with ESF. ESF induced a proportion of transitional cells to incorporate 55Fe in both F1 and F2. Transitional cells were the only cell type in which heme synthesis was dependent on ESF. in other cells of clearly nonerythroid morphology (mononuclear phagocytes and reticular cells), 55Fe incorporation occurred independent of ESF. Although the fractionation procedure employed is unsuitable for the separation of ERC from bone marrow, it permitted the enrichment of transitional cells, a cell type defined by morphology. Radioautography with 55Fe identified a proportion of these cells as ERC in both F1 and F2 fractions of bone marrow obtained from normal and polycythemic guinea pigs. Although there may be other cell types in F2 capable of responding to ESF, the present studies show that some transitional cells function as progenitors of erythroblasts because they respond to ESF by initiation of heme synthesis and by transformation into the earliest recognizable erythroid cells.

Animals↗

PubMed1977

On the yolk sac of the cat. II. Erythropoietic phases, ultrastructure of aging primitive erythroblasts, and blood vessels.

The phase of primitive erythropoiesis in the feline yolk sac lasts from the 14th to the 20th day after malting. The globular nucleated primitive erythroblasts are formed extravascularly to some extent, but they can be clearly distinguished from the endoderm. They do not undergo a denucleation and are still present in the circulating blood on the 45th day. Aging primitive erythroblasts are characterized by a loss of polysomes, by the appearance of long intracytoplasmic electron-lucent channels, and by a nuclear pyknosis which can turn into a karyolysis. Definitive erythropoiesis begins around the 17th day but, even by the 19th day, it is not particularly prominent. It ends around the 45th day. It is almost exclusively intravascular. The distinction of immature primitive erythroblasts from erythroblasts of the definitive series is difficult, because it is based upon only slight differences in the heterochromatinization, in the nuclear-cytoplasmic ratio, and in the organelle content of the cells. In the definitive series, the nuclear divisions follows the law of the rhythmical halving of the nuclear volume. The cells exhibit more clearly identifiable maturation stages here, and the 'checkerboard nucleus' is more distinct. The vascular endothelium is largely attenuated and moderately fenestrated; it lacks a distinct basement membrane. Organelle-rich adventitial cells are found in close apposition.

Aging↗

PubMed1975

Septate-like junctions in abnormal erythroblasts: cytochemical, ultrastructural and freeze-etch studies.

Ultrastructural studies of the bone marrow of a patient with refractory anemia revealed aberrant erythroblasts with unique cell junctions. Periodic structures linked adjacent processes on the same cell as well as surfaces of neighboring erythroblasts. Inclusions circumscribed by similar complexes were also present in the cytoplasm. The junction appeared in cross sections as two rigidly parallel unit membranes separated by 250-300 A interspace with two regular arrays of facing 70 A particles at intervals of 160-200 A. These intracellular specializations were present between erythroblasts at various stages of maturation and between, mono, bi or multinucleated erythroblasts. Junctions were permeable to lanthanum and many that appeared to be intracellular were demonstrated to be continuous with the extracellular space. The fact that others were not penetrated by lanthanum indicates that detachment of the interdigitating processes from cells of origin could have occurred. In freeze-etched replicas, distribution of membrane particles was random in areas of septate-like junctions, although parallel rows were sometimes observed both on A and B inner hydrophobic faces of the membrane leaflets. Junctional complexes in tissue culture appeared to have been disrupted and were not reestablished; however, inclusions resembling internalized junctions were observed associated with multivesicular bodies. Ineffective erythropoiesis and the resulting refractory anemia appear to be associated with the presence of the described anomalous junctional complexes.

Anemia, Aplastic↗

PubMed1976

Erythroblastic islands and extra-medullary erythropoiesis in chronic myeloid leukaemia.

Aspirates from bone marrow, spleen and liver were morphologically analysed in 15 untreated patients wich chronic myeloid leukaemia. Megaloblastic changes of the erythroblasts were found to be more common in the spleen and liver than in the bone marrow. A significant increase of 'erythroblastic islands', i.e. erythroblasts in contact with reticulum cells, were recorded in the leukaemia patients compared to 15 healthy controls. It is suggested that the presence of such formations may indicate an increased death rate of defective erythroblasts followed by phagocytosis into reticuloendothelial cells.

Bone Marrow↗

PubMed1992

Ion channels in human erythroblasts. Modulation by erythropoietin.

To investigate the mechanism of intracellular Ca2+ ([Cai]) increase in human burst-forming unit-erythroid-derived erythroblasts by erythropoietin, we measured [Cai] with digital video imaging, cellular phosphoinositides with high performance liquid chromatography, and plasma membrane potential and currents with whole cell patch clamp. Chelation of extracellular free Ca2+ abolished [Cai] increase induced by erythropoietin. In addition, the levels of inositol-1,4,5-trisphosphate did not increase in erythropoietin-treated erythroblasts. These results indicate that in erythropoietin-stimulated cells, Ca2+ influx rather than intracellular Ca2+ mobilization was responsible for [Cai] rise. Both Ni2+ and moderately high doses of nifedipine blocked [Cai] increase, suggesting involvement of ion channels. Resting membrane potential in human erythroblasts was -10.9 +/- 1.0 mV and was not affected by erythropoietin, suggesting erythropoietin modulated a voltage-independent ion channel permeable to Ca2+. No voltage-dependent ion channel but a Ca(2+)-activated K+ channel was detected in human erythroblasts. The magnitude of erythropoietin-induced [Cai] increase, however, was insufficient to open Ca(2+)-activated K+ channels. Our data suggest erythropoietin modulated a voltage-independent ion channel permeable to Ca2+, resulting in sustained increases in [Cai].

Adult↗

PubMed1975

Effects of heterologous anti-erythrocyte antibodies on the generation cycle of erythroblasts in rats.

An injection of anti-rat erythrocyte rabbit serum or its 7S globulin fraction into rats resulted in immunohemolytic anemia associated with a positive anti-gloublin test examined with anti-rabbit gammaglobulin serum. However, an injection of 19S globulin fraction from the anti-erythrocyte serum failed to cause immunohemolytic anemia, although it induced a transient decrease in red cell count. These results indicate that 7S antibodies are responsible for the induction of anti-globulin test positive, experimental immunohemolytic anemia. The ferrokinetic and stathmokinetic studies revealed the prolongation of generation time of basophilic and polychromatic erythroblasts in rats injected with anti-erythrocyte serum or its 7S globulin fraction. The results from in vitro [3H] thymidine incorporation experiments also confirmed this prolongation. The analysis of in vivo [3H] thymidine labeling of erythroblasts in rats which were given the 7S GLOBULIN ANTIBODIES SUGGESTED THE PROLONGATION OF THE G1 time of the erythroblasts. These results suggest that the effects of anti-erythrocyte antibodies on the generation cycle of erythroblasts are to prolong their G1 time and keep them dormant.

Anemia, Hemolytic↗