Haemoglobin synthesis in fused cells.

When primitive erythroid cells from 5-day-old chick embryos are exposed to inactivated Sendai virus they do not undergo haemolysis but fuse with other cells by the normal process of cytoplasmic coalescence. In this way cells actively engaged in the synthesis of haemoglobin may be fused with others that are not. In heterokaryons formed by the fusion of such erythroid cells with cells from established mouse or hamster lines, haemoglobin synthesis initially continues at a high level, but then declines and ceases altogether within a period of about 60 h. This decline affects the synthesis of both haem and globin and reflects the activity of specific regulatory mechanism, for under these conditions other chick proteins continue to be synthesized. The haemoglobin synthesized in the heterokaryons is entirely chick, and not mouse or hamster, haemoglobin.     

Haemoglobin synthesis in 28 obligatory cases for alpha-thalassemia traits.

In the Far East two types of alpha-thalassemia genes, namely alpha-thalassemia, (alpha-thal1), and alpha-thalassemia2 (alpha-thal2) exist. Definite diagnosis of the alpha-thal1 and alpha-thal2 traits is very difficult because their hematological findings are minimally abnormal or normal. This study attempts to characterize the heterozygotes by hemoglobin chain synthesis in reticulocytes from obligatory cases of the alpha-thal1 and alpha-thal2 traits. Twelve parents of babies with hemoglobin Bart's hydrops fetalis (obligatory alpha-thal1 trait) had the mean total radioactivity alpha/beta ratio of 0.76 +/- SD 0.04, while that of 7 normal controls was 1.06 +/- SD 0.04. The alpha/beta globin chain ratios of 16 cases, who were either parents or offspring of patients with hemoglobin H disease, were found to segregate into 2 groups, i.e. 0.78 +/- SD 0.03 (10 cases) and 0.9l1 and alpha-thal2 traits respectively. The hematological data of the first group showed definite hypochromic microcytic red cells, similar to those of the parents of the hydrops. The second group had significantly higher mean corpuscular hemoglobin than the first group, compatible with alpha-thal2 trait. Our globin chain synthesis study thus appears to be capable of discriminating normal, alpha-thal1 and alpha-thal2 traits.     

The suppression of Haemoglobin E synthesis

The blood of two infants with Haemoglobin E trait and a form of -thalassaemia (Haemoglobin H Disease) was examined and it was confirmed that the proportion of Haemoglobin A:E was higher than in uncomplicated Haemoglobin E trait.Haemoglobin H ( ₄ ^A ) was added to the haemoglobin solution from a Haemoglobin E trait carrier. This mixture was dissociated into its ₂, ₂ ^A and ₂ ^E subunits, and these were then recombined. The proportion of A:E had risen to that found in vivo in Haemoglobin E trait carriers with Haemoglobin H Disease.It is suggested that competition between ^A and ^E for -chains may be an example of the mechanism by which -thalassaemia interacts with -chain abnormal haemoglobins.     

Haemoglobin synthesis in Bueonoa confusa (Hemiptera)

Incorporation of labelled precursors to haeme and protein (δ-aminolevulinic acid and amino acids, respectively) by cultures of Buenoa confusa tissues, followed by acrylamide gel electrophoresis of proteins in the culture media, indicates that Hb is synthesized and assembled by ‘tracheal cells’ of the abdomen.     

Haemoglobin variants in mice.

Haemoglobin variants were studied in wild and laboratory house mice (Mus musculus), including standard and new inbred strains, using starch-gel electrophoretic technique. Single (Hbbs) or diffuse (Hbbd) types of haemoglobin were found in all of them. The embryonic haemoglobin pattern was different from although similar to that of the adult in all the strains. The haemoglobins revealed monomorphism in the inbred strains, while polymorphism was observed in non-inbred laboratory and wild mice.     

Alpha thalassaemia in British people.

Although alpha thalassaemia is rare in north Europeans, it has been identified in British people with no known foreign ancestry. Twelve such patients were studied, of whom eight shared a distinctive molecular defect, which was clearly different from defects seen in subjects of Mediterranean or South East Asian origin. A rare but specific form of alpha thalassaemia is therefore present in the British population. In addition, two patients from families of mixed racial origin were encountered who had a moderately severe form of thalassaemia (HbH disease) due to the inheritance of one form of alpha thalassaemia from the British parent and another type from the foreign parent. This shows the importance of careful genetic counselling of British patients with haematological findings of thalassaemia.     

Haemoglobin norfolk in nepali gorkhas.

Three instances of fast moving haemoglobins in heterozygous form have been found in Indian soldiers of Nepali Gorkha, during a routine screening for abnormal haemoglobins. The affected individuals were not related and seemed clinically well.     

Haemoglobin synthesis in inducible, uninducible and hybrid Friend cell clones

In clone 707 of the Friend virus-induced erythroleukaemic cell line less than 1% of the cells stain detectably for haemoglobin with benzidine. On treatment with 2% dimethylsulphoxide (DMSO) the fraction of staining cells increases to 70–80%. Line Fw has a similar origin but does not respond to DMSO although up to 7–8% of these cells stain for haemoglobin when they are grown in intraperitoneal perfusion chambers. Evidence is presented that clone 707 does not contain sub-populations of non-inducible cells nor does the Fw line contain a sub-population of inducible cells. A BUdR-resistant derivative of clone 707, designated clone 707B2/7, was isolated and shown to be incapable of incorporating ³H-thymidine. A thioguanine-resistant derivative of line Fw, designated clone FwT6/4, was also isolated and shown to be incapable of incorporating ³H-hypoxanthine. Hybrids were prepared by fusing cells of clone 707B2/7 and clone FwT6/4 in the presence of inactivated Sendai virus and selecting the hybrids in HAT medium. The properties of parental and hybrid cells were studied. The hybrids contain chromosomes from both parents and can be induced with DMSO to form an increased fraction of haemoglobinized cells.     

The sicca syndrome in thalassaemia major.

A 20 year old man with beta thalassaemia developed symptoms of the sicca syndrome. His serum contained rheumatoid factor and antinuclear antibodies. A biopsy specimen of labial salivary gland showed large accumulations of haemosiderin within the parenchymal cells of the acini. Although in this case the sicca syndrome could not be definitely distinguished from Sjögren''s syndrome, the patient''s HLA type was not the one usually associated with Sjögren''s syndrome. Histological appearances suggested that the causative factor of the sicca syndrome was iron overload owing to an intensive blood transfusion regimen.     

Survival and desferrioxamine in thalassaemia major.

A small randomised trial and observation of all patients homozygous for beta-thalassaemia in Britain born in or before 1963 indicated that those patients who had received average weekly doses of more than 4 g of desferrioxamine over the previous few years were less likely to die in the near future than were patients of similar ages who had received less, or no, desferrioxamine.     

Haemoglobin Bart's hydrops syndrome in Greece.

A case of haemoglobin Bart''s hydrops syndrome was characterised in a Greek family with a history of three other fetuses with hydrops. Family studies showed that both the mother and father carried alpha-thalassaemia genes, and globin-chain synthesis analysis of the present fetus showed a total absence of alpha-chain production. The haemoglobin composition of the fetus was similar to that seen in cases in south-east Asia, and analysis of DNA from the Greek case confirmed the total deletion of the alpha-chain genes. The extent of the deletion, however, differed from that seen in south-east Asian cases and included the loss of one of the embryonic zeta-chain genes. Thus the severe form of alpha-thalassaemia occurs in Greece but has arisen independently from the similar condition in south-east Asia. The condition must be considered in any woman of this racial background who gives a history of unexplained stillbirths.