The haemoglobin constitution of infants with the haemoglobin Bart's hydrops foetalis syndrome.
TL;DR: It has been possible to exclude the presence of fragments of α‐chain longer than II residues in the cells of these infants, and studies indicate that the syndrome results from a total deficiency ofα‐chain production.
Abstract: Summary. The haemoglobin constitution of 14 infants with the haemoglobin Bart's hydrops syndrome has been examined. Thirteen of the infants were stillborn or lived only a few minutes after delivery, but in one case an exchange transfusion was performed and the pattern of globin chain synthesis examined by an [H3]leucine incorporation experiment utilizing umbilical cord blood. These studies indicate that the syndrome results from a total deficiency of α-chain production. Furthermore, it has been possible to exclude the presence of fragments of α-chain longer than II residues in the cells of these infants.
In each infant a small quantity of haemoglobin was found which consisted of normal γ-chains in association with chains of unique constitution. A similar component was found in trace amounts in normal umbilical cord blood. This haemoglobin may be identical with haemoglobin Portland. It is suggested that the non-γ-chain of this haemoglobin is the product of a normal foetal haemoglobin locus which produces very small amounts of gene product in normal infants but which is capable of increased activity in the presence of a partial or total deficiency of α-chains.
Citations
More filters
TL;DR: The capacity of these cells to differentiate in vitro is investigated and it is reported here that they are induced by haemin to synthesise large amounts of haemoglobin; preliminary analysis indicates that this is predominantly of the embryonic type.
Abstract: STUDIES of the regulation of human erythropoiesis and haemoglobin synthesis at different phases of development are hampered by the lack of a self-sustaining culture in which erythroid differentiation can be examined, and by difficulties in obtaining erythropoietic tissue in embryonic and early fetal life1. New insights into the regulation of murine erythropoiesis have been obtained by the study of established cultures of erythro-leukaemic cells (Friend cells) which can be induced to differentiate in vitro2. Recently, Andersson et al. 3,4 have reported that the K562 human cell line, obtained from a patient with an acute transformation of chronic myeloid leukaemia (CML) has properties in common with erythroid cells. In particular, cells of this line contain glycophorin and spectrin in their membranes and synthesise minute amounts of haemoglobin, detectable by radioimmunoassay. We have investigated the capacity of these cells to differentiate in vitro and report here that they are induced by haemin to synthesise large amounts of haemoglobin; preliminary analysis indicates that this is predominantly of the embryonic type.
490 citations
TL;DR: A significant benefit of 12% in overall survival (OS) by donor availability for all patients with AML in CR1 without a favorable cytogenetic profile is revealed.
452 citations
TL;DR: Analysis of the cloned DNA confirms the linkage arrangement of the two adult α-globin genes (α1 and α2) previously derived from genomic blotting experiments and identifies two additional closely linked α-like genes.
442 citations
TL;DR: The Ontogeny of Globin Gene Expression and Molecular Cloning and Repetitive Sequence Elements Within GlobinGene Clusters are reviewed.
Abstract: INTRODUCTION 146 The Ontogeny of Globin Gene Expression 146 Globin Gene Mapping and Molecular Cloning 147 THE HUMAN ,8-LIKE GLOBIN GENES .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . . . . .. . .. . . . . 148 ,8-Like Globin Gene Fine Structure 148 ,8-Like Globin Gene Linkage . . . .... 151 Repetitive Sequence Elements Within Globin Gene Clusters 153 ,8-Globin Variants .... 153 DNA Sequence Polymorphisms Within the ,8-Like Globin Gene Cluster ..... 154
268 citations
TL;DR: Haemoglobin Constant Spring is an unusual variant which comprises only 1–2% of the total haemoglobin in heterozygotes, and when it is inherited together with an α-thalassaemia gene it gives rise to ha Hemoglobin H disease.
Abstract: Haemoglobin Constant Spring is an unusual variant which comprises only 1–2% of the total haemoglobin in heterozygotes. It has α-chains which are 172 residues long instead of the normal 141, and when it is inherited together with an α-thalassaemia gene it gives rise to haemoglobin H disease.
240 citations
References
More filters
TL;DR: In this article, a method for the separation of the α and β chains of human haemoglobin by chromatography on carboxymethyl-cellulose in 8 M -urea has been described.
1,425 citations
150 citations
TL;DR: In this article, the rate of globin chain production has been studied in patients with homozygous β-thalassaemia, heterozygous α-thalassemia, haemoglobin E-thallassemia and sickle-cell-thalassemia.
Abstract: Summary:
The rate of globin chain production has been studied in patients with homozygous β-thalassaemia, heterozygous β-thalassaemia, haemoglobin E-thalassaemia, and sickle-cell-thalassaemia, and compared with that in non-thalassaemic individuals. A partial or total deficit of β-chain synthesis has been demonstrated in all forms of β-thalassaemia. This results in the production of a large intracellular pool of α-chains, the kinetics of which have been worked out. The α-chains in this pool appear to contain haem and are unstable, rapidly becoming associated with the stromal fraction. These findings are examined in terms of the pathogenesis of the anaemia of thalassaemia.
143 citations
TL;DR: Since it had been demonstrated by Lee et al. (1964) that the tumour itself was the source of production of a substance having antidiuretic-hormone activity, a direct attempt to suppress this with antimitotic agents might prove a more effective measure.
Abstract: and because of the large numbers of tablets the patient was having to take. Furthermore, very frequent estimations of his electrolyte levels were required. Since it had been demonstrated by Lee et al. (1964) that the tumour itself was the source of production of a substance having antidiuretic-hormone activity, we felt that a direct attempt to suppress this with antimitotic agents might prove a more effective measure. The patient was therefore given a single dose of 40 mg. of nitrogen mustard (his weight at this time being 80 kg.; the dosage of the drug was 0.5 mg./kg.) and 10 days later the 9a-fluorohydrocortisone was withdrawn. Thereafter, serum sodium and potassium levels remained within normal limits; serum osmolarity rose and urine osmrlarity fell. For the first week after withdrawal of 9a-fluorohydrocortisone urine sodium loss increased again, but one month later had fallen to less than half its level before treatment. Over a follow-up period of three months the patient remained in normal electrolyte balance; no potassium or sodium supplements were required, and he complained only of a persistent cough.
138 citations