scholarly journals Changes in Globin Synthesis With Erythroid Cell Maturation in Sickle Thalassemia

Blood ◽  
1973 ◽  
Vol 41 (3) ◽  
pp. 353-357 ◽  
Author(s):  
A. Bank ◽  
L. W. Dow ◽  
M. G. Farace ◽  
J. V. ÓDonnell ◽  
S. Ford ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Cell Maturation ◽  
Erythroid Cell ◽  
Clinical Symptomatology ◽  
Mild Anemia ◽  
Black Patients ◽  
Biochemical Studies ◽  
Globin Synthesis ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract Biochemical studies of different groups of patients with sickle β-thalassemia (S-thal) are described. In a group of relatively asymptomatic black patients with sickle thalassemia, there is mild anemia and no clinical symptomatology. α and β-type (βA,βS, and γ) globin chain synthesis in these patients is balanced in bone marrow cells, although there is an excess of α-over β-type chain synthesis in peripheral blood. These mildly affected patients are in contrast to two other groups of S-thal patients of both Mediterranean and black extraction who have anemia and clinical symptomatology and in whom there is absent or more decreased βA-chain production.

scholarly journals Isolation and in vitro differentiation of human erythroid precursor cells

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 767-776
Author(s):  
HC Kim ◽  
PA Marks ◽  
RA Rifking ◽  
GM Maniatis ◽  
A Bank
Keyword(s):  
Precursor Cells ◽  
Cell Maturation ◽  
Erythroid Cell ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Erythroid Cells ◽  
Erythroid Precursor ◽  
Globin Synthesis ◽  
Chain Synthesis

There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24–48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha- globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia.

scholarly journals Isolation and in vitro differentiation of human erythroid precursor cells

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 767-776 ◽  
Author(s):  
HC Kim ◽  
PA Marks ◽  
RA Rifking ◽  
GM Maniatis ◽  
A Bank
Keyword(s):  
Precursor Cells ◽  
Cell Maturation ◽  
Erythroid Cell ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Erythroid Cells ◽  
Erythroid Precursor ◽  
Globin Synthesis ◽  
Chain Synthesis

Abstract There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24–48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha- globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia.

scholarly journals Asynchronous globin chain synthesis in rabbit reticulocyte lystates induced by hemin-controlled repressor

Blood ◽  
1978 ◽  
Vol 51 (4) ◽  
pp. 653-658 ◽  
Author(s):  
RS Franco ◽  
JW Hogg ◽  
OJ Martelo
Keyword(s):  
Globin Chain ◽  
Free System ◽  
Globin Chains ◽  
Reticulocyte Lysate ◽  
Chain Imbalance ◽  
Globin Synthesis ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed.

scholarly journals Globin chain synthesis in HbD (Punjab)-beta-thalassemia

Blood ◽  
1976 ◽  
Vol 47 (1) ◽  
pp. 113-120 ◽  
Author(s):  
RF Rieder
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Globin Chains ◽  
Mild Anemia ◽  
Thalassemia Trait ◽  
Chain Synthesis ◽  
Hbd Punjab ◽  
Globin Chain Synthesis

Abstract A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta- thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.

scholarly journals Absolute Rates of Globin Chain Synthesis in Thalassemia

Blood ◽  
1968 ◽  
Vol 31 (2) ◽  
pp. 226-233 ◽  
Author(s):  
ARTHUR BANK ◽  
ALBERT S. BRAVERMAN ◽  
JOYCE V. O’DONNELL ◽  
PAUL A. MARKS
Keyword(s):  
Peripheral Blood ◽  
Erythroid Cell ◽  
Absolute Rate ◽  
Globin Chain ◽  
Globin Chains ◽  
The Absolute ◽  
Α Chain ◽  
Chain Synthesis ◽  
Globin Chain Synthesis ◽  
Β Chain

Abstract The absolute rate of α chain synthesis per erythroid cell in the peripheral blood of patients with β thalassemia has been shown to be normal while that of β chains is markedly decreased or absent. The results indicate that α chains do not require the presence of β chains for their normal synthesis and release. In addition, γ chain synthesis does not compensate for the decreased β chain synthesis. A marked heterogeneity in the amount of β globin chains produced by different patients with β thalassemia is also prominent.

Globin Synthesis During Erythroid Cell Maturation in α Thalrssemia

Hemoglobin ◽  
1976 ◽  
Vol 1 (2) ◽  
pp. 135-151 ◽  
Author(s):  
W. G. Wood ◽  
G. Stamatoyannopoulos
Keyword(s):  
Cell Maturation ◽  
Erythroid Cell ◽  
Globin Synthesis

scholarly journals Defects in the synthesis of human haemoglobin

1978 ◽  
Author(s):  
Ρεγγίνα Σταθοπούλου
Keyword(s):  
Structural Changes ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Red Cells ◽  
Synthesis Rate ◽  
Structural Studies ◽  
Human Haemoglobin ◽  
Abnormal Haemoglobin ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

The work described is concerned with the biosynthesis of haemoglobin in human reticulicytes and bone marrow cells with particular reference to abnormal haemoglobins. The work in abnormal haemoglobins was supported by structural studies and involved a - and ß - chain variants, some of the latter being unstable. In some of the individuals with α or ß - chain variants, as well as in a number of subjects with β- thalassaemia, the estimation of the free α - chian pool was carried out. Using the same methodology, an attempt was made to detect chain fragments in the latter group of subjects. In the α - chian variants, attention was paid to the different proportions of the same α - chian abnormal haemoglobin in different individuals. Notably so in the case of haemoglobin G Philadelphia. The results supported the interpretation that here are four α - chian genes and that the α - G Philadelphia gene may occur together with threee, two or one normal α - chian genes respectively, the number of normal α - chian genes being potentially decreased by α - thalassaemia. With ß - chain variants a number of low proportion abnormal haemoglobins in the blood was studied. The globin chain synthesis pattern in the reticulocytes was compared with the haemoglobin composition in the mature red cells and the clinical condition of the subjects. Structural changes in haemoglobin were related to the rate of its synthesis. In some instances, both the synthesised amount of the variant was low as well as its proportion in the mature red cells. In others, notably haemoglobin E and Haemoglobin newcastle, the synthesis rate of the variant was normal but its proportion in the circulating red cells was low. Possible molecular mechanisms are either instability of the variant ß - chain of defective association into functioning polymer.

scholarly journals Retrovirus-mediated transfer of the erythropoietin gene in hematopoietic cells improves the erythrocyte phenotype in murine beta- thalassemia

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 928-933 ◽  
Author(s):  
JL Villeval ◽  
P Rouyer-Fessard ◽  
N Blumenfeld ◽  
A Henri ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Bone Marrow Cells ◽  
Elevated Serum ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Alpha Globin ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract Repeated injections of large doses of erythropoietin (Epo) have been shown to be of benefit in the treatment of murine and human beta- thalassemia. To determine whether Epo gene therapy could replace this treatment for long-term periods, lethally irradiated beta-thalassemic (Hbbd3th haplotype) and normal DBA/2J (Hbbd haplotype) mice were grafted with syngeneic bone marrow cells infected with a retroviral vector carrying the Epo cDNA. In normal mice, dysregulated Epo production induced elevated serum Epo levels (176 +/- 68 mU/mL), high hematocrit levels (73% +/- 8%), and elevated beta-minor globin chain synthesis. In contrast, in thalassemic mice, moderate increases in the hematocrit levels (from 33% +/- 1% to 43% +/- 9%), associated with limited increases in the initially elevated Epo levels (from 83 +/- 22 to 190 +/- 230 mU/mL), were recorded 2 months after transplantation. In mice in which the hematocrit increased most, from 33% +/- 1% before transplantation to 49% +/- 10%, the retroviral Epo gene expression induced a striking improvement of the beta-thalassemic syndrome. These mice exhibited normal or near-normal beta/alpha-globin chain synthesis ratios, induced by the activation of the beta-minor chain. This led to the elimination of the high amounts of unpaired alpha chains in erythrocytes and finally reduced the reticulocyte count despite the permanent Epo stimulation. These results show that efficient Epo gene expression corrects the erythrocyte phenotype of the mouse beta- thalassemic syndrome. However, the incidence of lethal polycythemia or of transient improvements indicates that the present strategy is only the first step toward such indirect gene therapy.

Frequencies of thalassemia in American blacks

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 981-986 ◽  
Author(s):  
HI Pierce ◽  
S Kurachi ◽  
K Sofroniadou ◽  
G Stamatoyannopoulos
Keyword(s):  
Black Males ◽  
Healthy Adult ◽  
Beta Thalassemia ◽  
Mean Corpuscular Hemoglobin ◽  
Alpha Thalassemia ◽  
Thalassemia Trait ◽  
Globin Synthesis ◽  
Chain Synthesis ◽  
Globin Chain Synthesis ◽  
American Blacks

Abstract The frequency of thalassemia was determined in a group of 541 healthy adult black males. Individuals with decreased mean corpuscular hemoglobin (MCH) values were evaluated further with hemoglobin analysis, iron studies, and globin chain synthesis. Of the males screened, 13.4% had MCH levels below 27.0 pg, while 1.4% had heterozygous beta thalassemia, 2.3% had iron deficiency, and 5.7% had globin synthesis findings compatible with the diagnosis of alpha thalassemia trait (alpha thalassemia-1). This study suggests that thalassemia is one of the most frequent hematologically depictable abnormalities in American blacks.

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