scholarly journals Sideroblasts

Blood ◽  
1954 ◽  
Vol 9 (3) ◽  
pp. 203-213 ◽  
Author(s):  
EUGENE KAPLAN ◽  
WOLF W. ZUELZER ◽  
CLAUDE MOURIQUAND

Abstract Bone marrow specimens from a large group of infants and children were studied with the prussian blue stain. Iron-staining granules were present in the normoblasts of all the subjects studied, including normal individuals and those with a large variety of hematologic disorders. The term sideroblast was proposed for normoblasts with nonstaining inclusions. The profound decrease in sideroblasts in iron deficiency anemia and their prompt increase following both iron therapy in vivo and the addition of iron to marrow cultures in vitro indicated that the estimation of normoblast iron granules provides a sensitive index of the availability of iron. In thalassemia and in lead poisoning, hemoglobindeficient erythrocytes were found despite the presence of abundant iron granules within the normoblasts. The presens of stainable nonhemoglobin iron in red cell precursors is a normal phenomenon and provides a useful adjunct for the study of iron metabolism.

2020 ◽  
Vol 3 ◽  
Author(s):  
Pete Hunter ◽  
Daniel Edwards ◽  
Christopher Miller ◽  
Erica Clinkenbeard

Background/Objective:   An estimated 37 million Americans have Chronic Kidney Disease (CKD), a condition in characterized by gradual decline in kidney function1. Patients with CKD are often afflicted with skeletal fractures, increasing morbidity and mortality. CKD has also shown a strong correlation with iron-deficiency anemia. The underlying mechanisms of how iron-deficiency anemia of CKD affects bone loss are not well understood. Based on RNA-sequencing results, we hypothesize that lactate dehydrogenase A (LDHA) may play a role in iron-deficiency mediated suppression of osteoblast differentiation and function.    Methods:   Mouse Progenitor Cells (MPC2) were incubated in osteogenic media along with deferoxamine (DFO) to induce differentiation in chronic iron deficiency; samples were collected after 7 and 14 days. Quantitative real-time PCR and western blot were used to validate LDHA mRNA and protein levels in DFO treated MPCs versus control cells. RNA levels of osteoblast genes and LDHA were also assessed in a pre-clinical mouse model of CKD.    Results:   In vitro, MPCs cultured in DFO media showed a significant increase of LDHA mRNA at 7 days (p=0.015) and returned to near control levels by day 14. Western blots showed a slight increase of total LDHA protein in DFO treated MPCs at 7 days and a large increase of protein at the 14-day mark (p=0.051). In vivo, CKD bone marrow showed a reduction in osteoblast gene expression (osteocalcin and type 1 collagen; p<0.05). LDHA mRNA expression was increased in CKD mice bone marrow when compared to wild-type mice (p=0.051), suggesting an inverse relationship.    Conclusion and Potential Impact:   Inappropriate activation of glycolysis and LDHA appears to play a role in iron-deficiency mediated suppression of osteoblast function in relation to CKD, both in vitro and in vivo. Further exploration of this relationship could be critical to the development of improved treatment options to maintain bone homeostasis during CKD. 


1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.


1963 ◽  
Vol 204 (1) ◽  
pp. 171-175 ◽  
Author(s):  
W. S. Ruliffson ◽  
J. M. Hopping

The effects in rats, of age, iron-deficiency anemia, and ascorbic acid, citrate, fluoride, and ethylenediaminetetraacetate (EDTA) on enteric radioiron transport were studied in vitro by an everted gut-sac technique. Sacs from young animals transported more than those from older ones. Proximal jejunal sacs from anemic animals transported more than similar sacs from nonanemic rats, but the reverse effect appeared in sacs formed from proximal duodenum. When added to media containing ascorbic acid or citrate, fluoride depressed transport as did anaerobic incubation in the presence of ascorbic acid. Anaerobic incubation in the presence of EDTA appeared to permit elevated transport. Ascorbic acid, citrate, and EDTA all enhanced the level of Fe59 appearing in serosal media. These results appear to agree with previously established in vivo phenomena and tend to validate the in vitro method as one of promise for further studies of factors affecting iron absorption and of the mechanism of iron absorption.


2014 ◽  
Vol 211 (5) ◽  
pp. 909-927 ◽  
Author(s):  
Adlen Foudi ◽  
Daniel J. Kramer ◽  
Jinzhong Qin ◽  
Denise Ye ◽  
Anna-Sophie Behlich ◽  
...  

The zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b’s adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow. We reveal strict, lineage-intrinsic requirements for continuous adult Gfi-1b expression at two distinct critical stages of erythropoiesis and megakaryopoiesis. Induced disruption of Gfi-1b was lethal within 3 wk with severely reduced hemoglobin levels and platelet counts. The erythroid lineage was arrested early in bipotential progenitors, which did not give rise to mature erythroid cells in vitro or in vivo. Yet Gfi-1b−/− progenitors had initiated the erythroid program as they expressed many lineage-restricted genes, including Klf1/Eklf and Erythropoietin receptor. In contrast, the megakaryocytic lineage developed beyond the progenitor stage in Gfi-1b’s absence and was arrested at the promegakaryocyte stage, after nuclear polyploidization, but before cytoplasmic maturation. Genome-wide analyses revealed that Gfi-1b directly regulates a wide spectrum of megakaryocytic and erythroid genes, predominantly repressing their expression. Together our study establishes Gfi-1b as a master transcriptional repressor of adult erythropoiesis and thrombopoiesis.


1981 ◽  
Vol 60 (2) ◽  
pp. 346-353 ◽  
Author(s):  
Kenichi Harigaya ◽  
Marilyn E. Miller ◽  
Eugene P. Cronkite ◽  
Robert T. Drew

1984 ◽  
Vol 4 (1) ◽  
pp. 216-220 ◽  
Author(s):  
J M Heard ◽  
S Fichelson ◽  
B Sola ◽  
M A Martial ◽  
B Varet ◽  
...  

A helper-independent Friend leukemia virus was used to infect bone marrow cultures. This virus induces myeloblastic leukemia in mice after a long latency period. Infection of the bone marrow cultures resulted in the in vitro production of myeloblastic leukemogenesis after a long latency period. Three steps were observed in the evolution of the infected cultures, and permanent cell lines were derived at each step. This allowed us to individualize three successive events in the course of the myeloblastic transformation: (i) an abnormal responsiveness to the physiological hormone granulo-macrophagic colony-stimulating factor, (ii) the acquisition of growth autonomy, and (iii) the acquisition of in vivo tumorigenicity.


Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 463-467 ◽  
Author(s):  
STAVROS HAIDAS ◽  
DOMINIQUE LABIE ◽  
JEAN-CLAUDE KAPLAN

Abstract A parallel decline of 2,3-diphosphoglycerate (2,3-DPG) and P50 of intracorpuscular hemoglobin is found in red blood cells during their in vivo aging. After 2,3-DPG depletion due to in vitro storage, the capacity to restore, 2,3-DPG in the presence of inosine is significantly impaired in senescent cells as compared with young cells.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5080-5080
Author(s):  
Elizabeth A Price ◽  
Renee Mehra ◽  
Stanley L. Schrier

Abstract Abstract 5080 BACKGROUND Anemia in the elderly is common, and associated with substantial morbidity and even mortality. Approximately one third of patients with anemia will have no discernable etiology for their anemia, that is, so-called unexplained or idiopathic anemia of aging. Prior reports have suggested that 5-15% of elderly patients with anemia will have an underlying myelodysplastic syndrome (MDS). The purpose of this study was to prospectively evaluate a cohort of elderly outpatients for underlying causes of anemia. METHODS Men and women 65 years and older with anemia as defined by World Health Organization (WHO) criteria and seen either at Stanford Hospital and Clinics (SHC) or VA Palo Alto Health Care Systems (VAPAHCS) underwent a comprehensive hematologic evaluation to determine the etiology of the anemia. Assessment included a complete blood count, red cell indices, review of the peripheral smear, and evaluation of iron and cobalamin status and renal function. Patients were categorized as having MDS if diagnosed by WHO criteria. If a bone marrow evaluation was not performed or was nondiagnostic, patients were categorized as “suspicious for MDS” if the MCV was > 100 fl without an alternate explanation, the platelet count was < 130 K/αL, the WBC was < 4 K/αL, or there was dysplasia on the peripheral smear. If no etiology was found, patients were categorized as having “unexplained anemia” of aging. RESULTS A total of 196 patients have enrolled, and 156 have completed their diagnostic evaluation to date. Of these 156, 52 (33%) had unexplained anemia, 33 (21%) were found to have anemia related to a definite or suspected underlying hematologic malignancy, 24 (15%) had anemia related to a nonhematologic malignancy, 20 (13%) had previously unrecognized iron deficiency anemia, and 8 (5%) had anemia due to renal insufficiency. Additional etiologies included anemia of chronic inflammation (5 patients), thalassemia (2 patients), alcohol abuse (1 patient), B12 deficiency (1 patient), hypogonadism (1 patient), other (2 patients). In 7 patients (4%) the evaluation was not complete. Of those categorized with anemia related to an underlying hematologic malignancy, 12 of 33 (36%) were given a formal diagnosis, including acute myeloid leukemia, chronic myelomonocytic leukemia, Waldenstrom's, and, in 8 patients, MDS. An additional 21 of 33 (64%) were categorized as being “suspicious for MDS”. One patient initially categorized as being “suspicious for MDS” developed worsening cytopenias and underwent bone marrow evaluation which confirmed the diagnosis of MDS. Those suspected but not confirmed to have MDS had a median WBC of 4.9 K/αL, median hemoglobin (hgb) of 10.8 g/dL, median platelets of 170 K/αL, median mean corpuscular volume (MCV) of 96 fL, and median red cell distribution width (RDW) of 14%. In comparison, those confirmed to have MDS had a similar median WBC of 5.3 K/αL, lower median hgb of 10.3 g/dL, similar median platelet count of 199 K/αL, higher median MCV of 106.3 fL,and broader median RDW of 17%. Of the 20 patients with iron deficiency anemia, the diagnosis was made by standard laboratory iron indices in 14 (70%), by response to iron supplementation in 3 (15%), and by bone marrow aspirate and clinical diagnosis, respectively, in 1 patient (5%) each. Six of the 20 (30%) patients normalized their hgb following iron repletion, 5(25%) increased the hgb by at least one g/dL but did not reach a normal hgb level, and in 9 (45%) this information was not available. DISCUSSION In our study of elderly community-dwelling patients referred to an outpatient hematology clinic, 8% of patients were formally diagnosed with an underlying hematologic malignancy, and 13% were suspected to have MDS based on a high MCV, dysplasia on the peripheral smear, or additional cytopenias. Thus, overall, 21% were likely to have an underlying hematologic malignancy. Of the patients suspected to have MDS, none required specific therapy. Thirteen percent of patients were diagnosed with iron deficiency anemia, primarily by iron indices. A high proportion (25%) of these patients did not normalize their hemoglobin with iron repletion, suggesting additional underlying disease processes. The clinical advantage of recognizing that iron deficiency has been corrected is that further potentially expensive and invasive evaluation such as additional endoscopy can be avoided. Disclosures Price: NIH: Research Funding. Mehra:NIH: Research Funding. Schrier:NIH: Research Funding.


Author(s):  
Fahima Hashem ◽  
Mohamed Nasr ◽  
Yomna Ahmed

Objective: The objective of this research was to formulate and evaluate iron oxide nanoparticles for treatment of iron deficiency anemia (IDA).Methods: Iron oxide nanoparticles were prepared by co-precipitation method and stabilized by coating with folic acid or chitosan. The prepared nanoparticles were characterized in vitro for morphology, particle size, zeta potential, crystallinity and ultraviolet-visible (UV-Vis) absorption. In vivo studies were performed to evaluate the efficacy of the prepared nanoparticles in treating iron-deficient anemic rats compared to the commercial iron product.Results: In vitro results revealed that particle sizes were 65.95±5 nm, 220.2±12 nm and 295.3±19 nm for uncoated iron oxide nanoparticles, folic acid-coated iron oxide nanoparticles and chitosan coated iron oxide nanoparticles, respectively. UV-Vis absorption spectrum and x-ray diffraction (XRD) patterns confirmed that the prepared nanoparticles were iron oxide nanoparticles. In vivo results indicated that folic acid-coated iron oxide nanoparticles showed effective restorative action, returning haemoglobin (Hb) concentration to normal levels, where not only complete recovery of Hb within short time from the anemic state to the high normal level, but also improved Hb concentrations compared to the commercial iron product.Conclusion: The results obtained in this research work clearly indicated a promising potential of folic acid-coated iron oxide nanoparticles for the effective treatment of IDA.


1955 ◽  
Vol 38 (3) ◽  
pp. 389-404 ◽  
Author(s):  
G. Lennard Gold ◽  
A. K. Solomon

The relative Na24 specific activity of red cells and plasma was measured at periods up to 30 hours following a single intravenous injection of Na24 in normal healthy young adults. The average specific activity of the red cells relative to that of the plasma at 24 hours and beyond was found to average 0.83 ± 0.05 in a series of five normal individuals, significantly different from 1.0. This indicates that all the intracellular Na is not exchangeable in 24 hours, and confirms earlier in vitro results. The red cell Na concentration in man was shown to be 12.1 ± 1.1 m.eq. Na/liter red cell, as measured in a series of nineteen normal healthy young adults. A theoretical analysis of the data on exchangeable cell Na suggests that the red cell Na (5.3 m.eq. Na/liter blood) is divided into a fast compartment comprising 4.25 m.eq. Na/liter blood, and a slow compartment comprising 1.07 m.eq. Na/liter blood. If these compartments are arranged in parallel, the flux between plasma and fast compartment is 1.32 m.eq. Na/liter blood hour, and that between plasma and slow compartment is 0.016 m.eq. Na/liter blood hour. Results of experiments on two patients with congenital hemolytic jaundice suggest that the fraction of slowly exchanging Na may increase with the age of the red cell.


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