The Bessis reticular cell, the hemoglobin 'switch' and the role of fetal hemoglobin: a hypothesis.

With the help of diverse factors, definitive erythropoiesis is induced by the junction of a pluripotential stem-cell with a specialized macrophage. In the normal adult marrow the latter becomes the reticular cell forming the core of an 'erythroblastic island'. It stays in close contact with all the erythroid cells descending from the stem-cell until their full maturation. While this contact lasts, only alpha and beta (delta) globin chains are produced. The production of gamma chains is inhibited. Stress forces the reticular cell to let the erythroid cells go. The stronger the stress, the earlier the separation. When free from the reticular cell, the erythroid cells stop producing beta chains and switch to form gamma ones. Increase in the volume of blood circulation is a potent stress. Since it is relatively enormous in the embryo and the fetus, most hemoglobin produced at these periods will be fatal. The important quality of fetal hemoglobin is its high oxidizability. It permits the senescent fetal red cell to be hemolysed intravascularly before any membrane alterations appear. The heme is dealt with by the placenta. Since no erythrophagocytosis has occurred, no bilirubin is formed. This process prevents bilirubin, which is toxic to the fetal liver, to reach it.

Decreased serum tuftsin concentrations in sickle cell disease.

The serum concentrations of the phagocytosis-stimulating peptide, tuftsin, were determined by radioimmunoassay in 21 patients with sickle cell disease and in 12 healthy controls. The mean serum tuftsin concentration was significantly lower in patient with haemoglobin SS disease (154.3 +/- 35.1 ng/ml; 308.6 +/- 70.2 nmol/l, P < 0.01) and in patients with haemoglobin SC and CC disease (180.9 +/- 42.7 ng/ml; 361.8 +/- 85.4 nmol/l, P < 0.05) than in healthy controls (228.7 +/- 46.7 ng/ml; 457.4 +/- 93.4 nmol/1). Tuftsin deficiency is an indicator of splenic hypofunction and may contribute to the increased susceptibility of patients with sickle cell disease to severe infection.

Persistence of in vitro lymphocyte response to tuberculin skin test negative children immunized with BCG in infancy.

PPD stimulated lymphocyte reactivity was tested in 119 children aged 11 to 12 years. The lymphocyte responses was evaluated by measuring the extent of tritiated thymidine incorporation by cultured cells. In a group of sixty-four tuberculin negative children who had been BCG vaccinated in the neonatal period, lymphocyte response was significantly greater than in a group of non-vaccinated tuberculin negative children matched for sex. The highest reactivity appeared in another group of children vaccinated in infancy and tuberculin positive. Lymphocytes from BCG vaccinated children retain some sensitivity to tuberculin even years after the BCG vaccination and even at the time when the skin reactivity disappeared.

Recurrent hemolytic-uremic syndrome. A report of two cases.

Two boys suffering from the hemolytic-uremic syndrome (HUS) are presented. One of them developed four episodes of the disease beginning at infancy, the other one had at least two episodes which were associated with mild portal fibrosis of the liver. Between the attacks of the disease, the children were completely healthy, and no renal or hematological abnormalities were detected. Both patients are now physically and mentally well developed healthy young men. The relatioship between HUS and thrombotic thrombocytopenic purpura is briefly discussed.

Decreased antihaemophilic globulin and leucocyte response to epinephrine in preterm infants.

Twenty-one preterm and 23 term neonates, 13 splenectomized children and one with congenital asplenia, and 20 normal children were examined for plasma antihaemophilic activity and for blood leucocyte levels before and 30 minutes after a subcutaneous injection of epinephrine 0-01 mg/kg. The basal values for antihaemophilic activity were similar for the 4 groups. The response to epinephrine was a trivial rise in antihaemophilic activity in the preterm group, while the rise in the term newborns was comparable to that of the normal children. The asplenic children all showed a trivial rise. The leucocyte response was also negligible in both the preterm neonates and asplenic groups, while in the term infants it was comparable to that seen in the normal children. These results may indicate an incapacity of the preterm newborn infant's reticuloendothelial system and spleen to react to other challenges, such as bacterial infection.

Acute neonatal isovaleric acidemia. A report of two cases.

Two fatal cases of the fulminant type of isovaleric acidemia are described. Attention is drawn to the existence of two forms of the disease, the severe "Newman" type, occurring in the first week of life and the milder "Tanaka" type, with a later onset. The importance of ruling out isovaleric acidemia in any newborn infant with acidosis is emphasized.

The effect of Tuftsin on the nitrous blue tetrazolium reduction of normal human polymorphonuclear leukocytes.

The influence of Tuftsin, the synthetic phagocytosis-stimulating tetrapeptide (L-threonyl-L-lysyl-L-prolyl-L-arginine), on the nitrous blue tetrazolium (NBT) reduction by human polymorphonuclear leukocytes was investigated. It was found that this substance increases the NBT reduction by approximately as much as endotoxin. Other tetrapeptides do not share this property. When Tuftsin analogs are added to the cell suspension and incubated, they prevent the action of both Tuftsin and endotoxin but not of methylene blue. When washed of the analogs, the cells regain the property to be activated by both Tuftsin and endotoxin. It appears that methylene blue on one hand and Tuftsin and endotoxin on the other hand have different sites for their actions. We suggest that whereas methylene blue diffuses into the cell and acts directly upon the hexosemonophosphate shunt activation, Tuftsin and endotoxin appear to act on the cell membrane binding to specific receptors. By treating the cells with Tuftsin analogs, we probably block these receptors.