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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serial microscopic immunodiffusion assays of F cells, i.e., erythrocytes that contain fetal hemoglobin (HbF), in four individuals recovering from anemia demonstrate initial increases in the percentage of circulating reticulocytes that contain HbF (F reticulocytes) and subsequent increases in the percentage of mature erythrocytes that contain HbF (F erythrocytes). In one individual responding to therapy for iron-deficiency anemia, the average percentage of F reticulocytes increased from 4.8+/-1.1 to 16.0+/-2.8% (mean+/-SD), while the mean level of F erythrocytes increased from 3.5+/-0.7 to 7.2+/-0.6%. Two normal children with transient erythroblastopenia exhibited F reticulocyte percentages of 71.3+/-6.7 and 41.5+/-1.5%, respectively, when erythropoiesis resumed. With recovery these values fell to finally measured values of 33.7+/-4.7 and 12.6+/-1.1%, respectively. In an adolescent with sickle cell anemia, F-reticulocyte percentages fluctuated between 0.6+/-1.1 and 34.0+/-2.8% and paralleled the rise and fall of total reticulocytes associated with therapy for a nasopharyngeal carcinoma. Such findings suggest that first, the production of F cells and non-F cells are separately regulated. Second, F-cell production is preferentially stimulated during escape from erythropoietic suppression and selectively depressed at the start of suppression. Third, during escape from erythropoietic suppression, F-cell production in vivo resembles that reported for in vitro cultures of erythroid stem cells. Fourth, individuals with sickle cell anemia, like individuals without hemoglobinopathies, can change their relative level of F-cell production.
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PMID:Production of erythrocytes that contain fetal hemoglobin in anemia. Transient in vivo changes. 42 49

Human globin messenger RNA (mRNA) prepared from erythroid cells of patients with sickle cell anemia has been translated in Xenopus laevis oocytes. Addition of hemin to the injected mRNA causes total globin synthesis to increase and the ratio of alpha- to betas-globin synthesis (alpha/betas ratio) to approach unity. To determine the effect of the length of the poly-(A) segment on human globin mRNA stability, 10 S globin mRNA was fractionated into poly-(A)-poor fractions by oligo (dT)-cellulose column chromatography. When oocytes are injected with each of these fractions, translation of the poly-(A)-rich globin mRNA is sustained for a longer period than that of the poly-(A)-poor mRNA. Regardless of the mRNA fraction injected, the alpha/betas ratio of the synthesized globin decreases as the injected oocytes are incubated for longer periods. The results indicate that in frog oocytes poly-(A)-rich mRNA has greater translational stability than poly-(A)-poor mRNA, AND beta-mRNA has greater stability than alpha-mRNA with comparable poly-(A) content.
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PMID:Translation and stability of human globin mRNA in Xenopus oocytes. 103 8

Sixteen episodes of acute anaemia necessitating urgent blood transfusion have been investigated in 13 children with sickle cell anaemia. In five out of seven episodes there was evidence of increased haemolysis while in 10 out of 16 episodes a profound fall in reticulocyte count indicated marrow erythroid cell failure. Cold agglutinins active at room temperature were detected in 13 episodes, and anti-I specificity was demonstrated in 11. Warmed blood of homologous ABO and Rhesus groups was administered without complication despite difficulty with cross-matching. The exacerbation of anaemia was not due to folate lack, glucose-6-phosphate dehydrogenase deficiency or splenic sequestration, and an infectious agent appeared responsible. The degree of anaemia in homozygous sickle cell disease is usually constant during asymptomatic periods. An episode of sudden profound anaemia (anaemic crisis) may, however, result from marrow hypoplasia, an exacerbation of haemolysis, splenic sequestration, or folate deficiency.
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PMID:Anaemic crisis in sickle cell disease. 115 Aug 83

Electron microscopic studies of bone marrow aspirates obtained from patients with homozygous sickle cell anaemia (HbSS) were fixed immediately without attempts to deoxygenate the samples. Erythroblasts and normoblasts in these preparations were devoid of haemoglobin polymers or other indications of sickling. Furthermore, the nucleated erythroid cells from sickle-cell patients presented an ultrastructural morphology indistinguishable from that of identically-processed erythroid cells in marrow samples from normal human volunteers. This report presents a description of the ultrastructural features of pronormoblasts and normoblasts in normal and sickle-cell marrows and stresses the essentially normal appearance of nucleated erythroid elements in sickle cell anaemia. Exposure of sickle-cell marrow aspirates to nitrogen at 37 degrees C for 30 min resulted in haemoglobin polymerization in most erythrocytes and reticulocytes but only in 10-20% of the nucleated erythroid cells. Haemoglobin polymers in the form of intertwining fibre meshworks were observed in reticulocytes, orthochromatic and polychromatophilic normoblasts, but were absent in basophilic normoblasts and pronormoblasts. The results suggest that the concentration of haemoglobin in intramedullary normoblasts may be the limiting factor determining the predisposition of these cells to undergo sickling as well as the pattern of haemoglobin aggregation. Under the physiological conditions prevailing in the marrow, haemoglobin concentration in normoblasts may be insufficient to result in aggregation and polymerization.
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PMID:Ultrastructural studies of the bone marrow in sickle cell anaemia. II. The morphology of erythropoietic cells and their response to deoxygenation in vitro. 120 Dec 49

Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.
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PMID:Lipid synthesis in human erythroid cells: the effect of sickling. 124 18

We have compared the sequence of the 5' hypersensitive site-2 (5'-HS-2) of the locus control region (LCR) from a sickle cell anemia (SS) patient homozygous for haplotype 19 and with low levels of fetal hemoglobin (HbF), with the same sequence from an SS patient homozygous for haplotype 3 and with high levels of HbF. Several nucleotide variations were present in the 5'HS-2 of the haplotype 19 individual. One is the A----G at position -10905 that creates an Sp1 binding site GCCCC (A----G)CCCC. A second is the T----G at position -10924 in a sequence that binds both erythroid and ubiquitous factors and exhibits high homology to the long terminal repeat of the Moloney leukemia viruses and Friend murine leukemia virus. Other differences were in the two AT-rich stretches of DNA, and an A----T substitution at position -10390. Dot-blot analyses of amplified DNA from several SS patients showed that these variations are specific for beta S chromosomes with haplotype 19. We also examined the 5'HS-2 sequence from an SS patient who is homozygous for haplotype 19, but has abnormally high levels of HbF (greater than 20%). We observed a cross-over that has placed sequences similar to the 5'HS-2 of haplotype 3 in juxtaposition to the 5' flanking regions of haplotype 19. Thus, a beta S chromosome with haplotype 19 but having a 5'HS-2 (LCR) characteristic for haplotype 3 is associated with high gamma-chain expression. We postulate that factors produced under conditions of hematopoietic stress, together with genetic determinants on the haplotype 3-like LCR sequences, allow for high level expression of gamma-globin genes.
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PMID:Sequence variations in the 5' hypersensitive site-2 of the locus control region of beta S chromosomes are associated with different levels of fetal globin in hemoglobin S homozygotes. 137 Jun 46

DNA-synthesis state of circulating burst forming unit-erythroid (BFU-E) was evaluated in patients with sickle cell anemia and correlated with percent of fetal hemoglobin synthesized in the BFU-E-derived cells. Percentage of S-phase BFU-E inversely correlated with percent fetal hemoglobin synthesized in the BFU-E-derived cells (simple linear correlation coefficient, r = -0.8, P = 0.0302; polynomial regression, R = -0.99, P = 0.0002). This observation is of relevance to our understanding of the relationship between the developmental stage of the erythroid progenitors and expression of globin genes.
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PMID:Relationship between cell-cycle state of erythroid progenitors and fetal hemoglobin synthesis. 137 72

A new hematopoietic growth factor (Steel factor) has been identified which stimulates erythroid proliferation both in vitro and in vivo. We evaluated the influence of recombinant Steel factor on hemoglobin synthesis in peripheral blood (PB) BFU-E-derived cells from normal donors by radioimmunoassay (RIA) and compared it with stimulation with GM-CSF and interleukin-3 (IL-3). Only Steel factor stimulated a significant increase in BFU-E-derived colony size and a significant increase in fetal hemoglobin (HbF) in BFU-E-derived erythroblasts from 0.49% +/- 0.27% to 6.33% +/- 1.11% in serum-deprived media and from 1.88% +/- 0.24% to 11.17% +/- 0.91% in serum. To determine whether this influence on hemoglobinization also occurred in sickle cell disease, we studied 13 patients with sickle cell disease. In serum-deprived conditions, there was a significant increase in the number and size of BFU-E-derived colonies with Steel factor that was dose-dependent. In addition, the proportion of HbF in progenitor-derived cells increased by 66% from 4.1% +/- 0.6% to 6.8% +/- 1.2% with Steel factor. In serum-containing conditions studied in 12 patients, the increase in percentage of HbF was even greater, from 10.7% +/- 0.9% in control cultures to 22.5% +/- 2.6% with Steel factor. These increases in percentage of HbF were significant and dose-dependent. An increase in percentage of HbF was observed in erythroblasts harvested on day 11, 14, and 18 of culture. A decrease in mean picograms of total Hb per cell after coculture with Steel factor was noted, suggesting that growth kinetics influenced complete hemoglobinization. In serum-deprived conditions, picograms of HbF per cell was not affected by Steel factor, and in serum-containing conditions that augment in vitro HbF production it was enhanced. Thus, Steel factor stimulated a significant increase in percentage of HbF in erythroid cells from normal donors and patients with SCA in vitro.
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PMID:Influence of steel factor on hemoglobin synthesis in sickle cell disease. 137 91

In the past 8 years, it has become apparent that some cytotoxic drugs that interfere with DNA replication can reprogram erythroid progenitors to switch from adult hemoglobin to fetal hemoglobin (HbF) production. Hydroxyurea has now been shown to substantially increase HbF in patients with sickle cell anemia. Since HbF interferes with sickle hemoglobin polymerization, hydroxyurea may become an important therapeutic agent for patients with sickle cell anemia.
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PMID:Hydroxyurea induction of fetal hemoglobin synthesis in sickle-cell disease. 137 74

Blood erythroid progenitors (BFU-E) from patients with sickle and thalassemic syndromes were compared with those from normal individuals. The day of maximal colony formation in methyl cellulose was slightly later in the cultures from the patients with hemoglobinopathies than in the normal cultures. The number of colonies/100,000 mononuclear cells was similar in all cultures on day 13, but was higher in the hemoglobinopathy cultures on the day of maximal growth. The number of BFU-E/mL of blood was significantly higher than normal at all times in both sickle cell anemia and thalassemia. The proportional synthesis of gamma globin was twice normal in all sickle cultures, and 4 times normal in those from beta+-thalassemia. Hemin and interleukin-3 increased the numbers of erythroid colonies in all cultures, but did not consistently alter the globin synthesis patterns. Each progenitor population has a unique pattern in terms of time course, number of BFU-E, and level of gamma globin synthesis. These features indicate distinct types of BFU-E, or differences in accessory cells, or both, which distinguish blood-borne erythropoiesis in normals and those with hemoglobinopathies.
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PMID:Sickle and thalassemic erythroid progenitor cells are different from normal. 148 17


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