AT was shown to be a useful intervention that can prevent permanent trauma and support children and parents during intrusive interventions.

We have previously found that the inhibitory effect of hemoglobin F (Hb F) on the polymerization of Hb S proceeds via the formation of asymmetrical hybrid tetramers of the type a2ts. Examination of the gelling properties of binary mixtures of Hb S and several Hb variants now shows that, among the y chain amino acid residues that differ from those of the P chain, residues y80 (EF4) and 'y87 (F3) are at least partly responsible for this inhibition. Furthermore, we find that mixing Hb A2(a2h2) with Hb S strongly inhibits gelling to an extent similar to that seen with Hb S/Hb F mixtures; this inhibition is attributable to amino acid differences between the 5 and P chain sequences at positions 522 (B4) and 587 (F3). Therefore, residues 22, 80, and 87 of the f chain appear to be involved in intermolecular contact sites that stabilize the deoxy Hb S polymers. The capacity of some Hb variants to facilitate or impair the polymerization of Hb S is now well known (1). It has long been recognized that these effects correlate with the clinical severity of genetic variants of sickle cell disease in which two major Hb components coexist in the erythrocytes (2). Our laboratory has developed the use of binary Hb mixtures (Hb X + Hb S) to map the residues involved in the interactions between Hb S tetramers in the polymer (3). The inhibitory effect of Hb F on the polymerization of Hb S has been well documented (1). More recently, it has been shown that this inhibition depends on the formation, in Hb S/Hb F mixtures, of asymmetrical hybrid tetramers of the type a2lS3y. Such an inhibitory effect did not occur with the formation of a2t3S#fA hybrids (4,5). Thus, the replacement of one of the Os chains of Hb S by a y chain appeared to have a strong inhibitory effect on polymerization. In the present article we will define part of the structural basis of this inhibition. In addition, we report a prominant inhibitory effect of Hb A2, on polymerization in mixtures with Hb S and provide data concerning the structural basis of this inhibition. METHODSHemolysates were made from blood' samples obtained after informed consent from donors with sickle cell anemia (SS) documented in our Heredity Clinic. The erythrocytes from these donors contained less than 5% (mean) Hb F and were used without further purification. (MGCs) were determined at 240C as described (6). It should be noted that we perform this assay in a manner such that the MGC values closely approximate the values we obtain by measuring the supernatant Hb concentration after highspeed centrifugation of the gel: the Hb mixture is fully deoxygenated for at least 40 min before its concentration is allowed to rise very slowly (by the evaporation of the solvent), and the determination is considered reliable only if the final Hb concentration is less than 2 g/dl higher than the starting concentration and if the total duration of the procedure from the time evaporation is begun is at least 30 min but less than 2 hr. For each mixture, repeat MGC determinations differed from the mean...

Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause.

The amino acid residues involved in the areas of contact that stabilise the haemoglobin S polymer fibre seem to be the same ones that stabilise the basic unit of the deoxyhaemoglobin S crystal: the Wishner-Love double strand. The haemoglobin S fibre is probably formed by a unique packing of these double strands.

In patients with betao thalassaemia from Ferrara, beta globin mRNA sequences are either absent or structurally abnormal while in betao thalassaemia in Catania, beta globin mRNA sequences are present. In deltabeta thalassaemia there is a deletion of beta-like globin genes, while in betao Catania DNA, no beta globin gene deletion is detectable.