Pattern of maternal F-cell production during pregnancy.

Maternal haemoglobin F production has been monitored in 11 normal pregnancies, with an immunofluorescent technique. In all cases there was a significant increase in the number of F-cells which reached a peak at 18-22 weeks' gestation. Comparison of the numbers of F-cells with the percentage haemoglobin F determined chemically indicated that the increase in maternal haemoglobin F synthesis results from an increased production of F-cells rather than from an increased synthesis of haemoglobin F by the F-cells.

G gamma delta beta thalassaemia and g gamma HPFH (Hb Kenya type): comparison of 2 new cases.

Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.

Mild sickle-cell anaemia in Iran associated with high levels of fetal haemoglobin.

Sixteen subjects, with sickle-cell anaemia, all Iranians (ages 3 to 56 years), with very mild symptomatology are reported. Some of the subjects had been totally asymptomatic. Splenomegaly was noted in 9 cases.

Inheritance of F cell frequency in heterocellular hereditary persistence of fetal hemoglobin: an example of allelic exclusion.

Two kindreds are described in which F cell frequency is inherited. These families differ in ethnic origin, the mean quantity of HbF per F cell, and in G gamma: A gamma ratios. Heterozygotes have approximately 50% F cells while homozygotes have close to 100%.

Haemoglobin Radcliffe (alpha2beta299(Gi)Ala): a high oxygen-affinity variant causing familial polycythaemia.

Three members of an Oxfordshire family have polycythaemia. In each case their whole-blood oxygen affinity is increased. This is due to a previously undescribed haemoglobin variant which has been named haemoglobin Radcliffe (alpha2beta299(Gl)Ala).

Haemoglobin switching during development in normal and hypophysectomised fetal sheep.

Haemoglobin synthesis has been studied in fetal sheep. The switch from gamma to beta chain synthesis occurs rapidly between 130 and 150 days. Fetal hypophysectomy delays the rate of switching but the timing of the onset of the switch is not under pituitary control.

Invasion and growth of Plasmodium falciparum in different types of human erythrocyte.

The susceptibility of human red blood cells to invasion by Plasmodium falciparum was investigated in microtissue cultures with different populations of erythrocytes containing fetal haemoglobin (HbF). Preferential invasion of HbF-containing erythrocytes was observed with umbilical cord blood. The parasites showed no preference for HbF cells in blood from a subject with hereditary persistence of fetal haemoglobin (HPFH).

Globin synthesis in normal human bone marrow.

Globin synthesis has been studied by in vitro labelling with radioactive amino acids in 60 normal human bone-marrow samples. Under the conditions routinely used to fractionate alpha and beta chains by chromatography alpha/beta production ratios ranging from 0.5 to 1.

The Negro variety of hereditary persistence of fetal haemoglobin is a mild form of thalassaemia.

Further studies have been carried out on blood of the 15-year-old Negro male from Baltimore who was the first reported case of the homozygous state for hereditary persistence of fetal haemoglobin. His red cells contain only Hb F; Hbs A and A2 have never been detected. Over a 15-year period of follow up the red cells of this individual have shown persistent microcytosis with reduced MCH and MCV values.

A model for the persistence or reactivation of fetal haemoglobin production.

Normal adults may have two distinct erythroid precursor populations, a major one which produces only adult haemoglobin (HbA), and another which produces HbA and fetal haemoglobin (H0F) (F cells). Persistence or apparent reactivation of HbF production in adults results from differential selection of these F cells, except in those rare conditions which are due to specific deletions of D.N.

Delta-beta-thalassemia is due to a gene deletion.

DNA has been prepared from peripheral blood or cultured skin fibroblasts obtained from three Sicilian and one Greed deltabeta-thalassemia homozygotes. Globin-gene analysis was carried out using a cDNAbeta probe, and the results indicate that deltabeta-thalassemia has arisen from a deletion of the beta-globin genes. A similar result was obtained using DNA prepared from cultured skin fibroblasts from an individual homozygous for the Negro form of hereditary persistence of fetal hemoglobin (HPFH).

Fetal haemoglobin and malaria.

The distribution and growth of Plasmodium falciparum was compared in red blood-cells containing either adult or fetal haemoglobins. In in-vitro cultures, cord blood-cells were invaded more readily, but there was a paucity of parasites in cells containing haemoglobin F in the blood of infected infants aged 3-6 months. These findings suggest that P.

A direct estimate of the number of human gamma-globin genes.

The number of genes specifying human gamma-globin has been determined directly by hybridization of complementary DNA to total human DNA. The complementary DNA was enriched in sequences specific for gamma-globin genes by transcribing globin mRNA isolated from fetal reticulocytes with viral reverse transcriptase, and collecting the material which does not back-hybridize to adult globin mRNA. When hybridized in cDNA excess to DNA, very similar values are found for gamma-gene number as for beta-gene number, suggesting two or at most three gamma-globin genes per haploid human genome.

Assay of thalassaemic messenger RNA in the wheat germ system.

Messenger RNA(mRNA) has been prepared from reticulocytes obtained from patients with different types of thalassaemia and assayed in the wheat germ system. Since normal human reticulocyte mRNA directs the synthesis of equal numbers of alpha- and beta-globin chains in this system it offers a rapid and simple technique for assaying mRNA in the thalassaemic disorders. In mRNA from beta+ thalassaemics the deficiency of beta-globin synthesis mirrored that observed in intact reticulocytes while that prepared from patients wiht haemoglobin H disease gave alpha/beta globin chain production ratios which showed consistently greater imbalance than was found in reticulocytes.

The patterns of fetal haemoglobin production in leukaemia.

Elevated levels of haemoglobin F (Hb F) have been foudn in a wide range of haematological malignancies, but very high levels were found only in juvenile chronic myeloid leukaemia (JCML), and erythroleukaemia occurring in infancy. In both these disorders a reversion to a fetal form of erythropoiesis may occur, as judged by both the structure of the Hb F and by the disappearance of Hb A2 and the carbnoic-anhydrase isozymes during the course of the illness. The clinical picture of JCML is not always associated with a reversion to fetal erythropoiesis; there appears to be a heterogeneity of conditions with this clinical label.