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A marked sensitivity of CLL lymphocytes to hydrocortisone in vitro was demonstrated in each of the 25 patients tested. The sensitivity was manifested by the eventual lysis of the affected cells. Malignant lymphocytes from 8 out of 14 ALL patients were found also to be in vitro sensitive, whereas CML cells, AML cells, normal BM cells, thymocytes, peripheral blood lymphocytes, and polymorphonuclear cells were resistant. Within a tested CLL lymphoid suspension it is proven that the hydrocortisone causes the specific lysis of the malignant cells leaving the normal lymphocytes undamaged. The cytolysis is not an immediate action, but is expressed within 7–8 hr of incubation. However, 30 min incubation with the hormone is sufficient for the cytolytic effect to occur 20 hr later. The possible mechanisms involved in the specific glucocorticoid induced cytolysis are discussed.

Thymic precursor cells (prothymocytes) comprise a large proportion of the fetal thymic cell population, but are less frequently encountered in the postnatal thymus, where they compose < 1% of the entire population. In the present study we attempted to characterize a number of properties of the prothymocytes obtained from human fetal thymic tissues after depletion of the E-rosette thymocyes on a Ficoll-Hypaque gradient. The prothymocytes are larger than the thymocytes and show a different nuclear chromatin pattern. This subset of cells lacks the E-rosetting and natural-attachment capacities and, unlike thymocytes, does not bind the lectin peanut agglutinin. Human prothymocytes are highly sensitive to the in vitro cytolytic effect of hydrocortisone, whereas the thymocytes are resistant. Long-term in vitro culture of prothymocytes resulted in the expression of thymocyte characteristics together with a burst of mitotic activity. Results of this study indicate that the rate of the prothymocyte proliferation is regulated by the small thymocytes present in the same suspension.

Synchronized erythroid cell cohorts were cultured for up to 6 days with and without added erythropoietin. The presence of erythropoietin in the medium was found indispensable for the synchronized differentiation and maturation of those cell populations. The appearance, during maturation in vitro, of a soluble cell component that is capable of inducing hemoglobin producation by polysomes isolated from undifferentiated blast cells is described. The same polysomes with their isologous soluble cell component were unable to produce this protein. These results confirm earlier observations made on synchronized rabbit cell populations in vivo.

A transferrin-free serum, produced by removing the siderophilin with a specific antitransferrin antibody, was incapable of stimulating the entry of iron into reticulocytes, unless it was reconstituted with pure transferrin-iron complex. These observations militate against the existence of serum factor(s), other than transferrin, capable of stimulating the incorporation of iron into reticulocytes. Comparing the effects of whole serum, pure transferrin, transferrin-free serum, and the latter reconstituted with pure transferrin, it was found that normal, pooled human serum augmented the utilization of intracellular iron for heme production, which transferrin alone did not achieve.

In view of the erythroid hyperplasia found in the bone marrow of subjects with chronic iron deficiency anemia, the delayed appearance of reticulocytosis following iron therapy is unexplained. Profound disturbances were observed in some biochemical functions of the bone marrow cells isolated from such patients. There was a substantial decrease in the cellular nucleic acid content, associated with a marked drop in the rate of 3H-thymidine incorporation into DNA. The utilization of 59iron and of glycine-2-14C for heme production, and of the latter compound for protein synthesis was also reduced, as compared to the findings in bone marrow cells from normal subjects. These metabolic alterations returned to the normal pattern in the bone marrow cell suspensions obtained from the patients following recovery after iron therapy. The possible implications of these findings are discussed in the light of available information.

Specific antisera with high antibody titers could be prepared against adult, cord blood, dog and rabbit hemoglobin solutions. These sera were employed to study the antigenic properties of the above hemoglobins. Common antigenic properties could be detected between hemoglobin solutions prepared from human, canine and rabbit blood. No immunologic difference could be found between the fetal fractions of adult human blood, cord blood and thalassemia patients’ hemoglobin solutions.

Immune sera produced against adult human, fetal, canine and rabbit hemoglobin solutions were found to agglutinate specifically the papain-treated red cells of the respective donors to a high titer. Intact red cells were also specifically agglutinated by the same antibody-containing sera in the presence of dextran, suggesting that the antibodies produced are incomplete ones. A marked shortening of the life span of rabbit erythrocytes followed the intravenous injection of anti-rabbit hemoglobin serum into normal rabbits. The possible implications of the above findings in human pathology are discussed.

In nine patients with various diseases and in two normal subjects, administration of acetylsalicylic acid (aspirin) in amounts of 3-4 Gm. per day produced a drop in serum iron. This drop could not be explained by chemical interference with the determination, by blood loss, impaired absorption or increased excretion of iron. In addition, it was shown that during administration of salicylates the survival time of the red cells was diminished. It is suggested that salicylates might produce anemia not only by gastrointestinal bleeding but also by interference with the metabolism of iron through some unknown mechanism.

Folic acid determinations were carried out on whole blood and serum by means of three microbiologic assays. The total folic acid (conjugated and free pteroylglutamic acid and folinic acid) was determined by L. casei, free pteroylglutamic acid and folinic acid were determined by the use of Strep. fecalis, and P. cerevisiae was employed for the determination of folinic acid (citrovorum factor).In sixty-four pregnant women with anemia, folic acid as well as serum iron and serum vitamin B12levels were determined. In thirty-five of them, significantly low folic acid values were found in whole blood and serum when compared with values in normal subjects. Low folic acid values were frequently associated with low serum vitamin B12and low serum iron concentration. The mechanism of the development of folic acid deficiency in pregnancy is discussed.

INTERSTITIAL pneumonia may appear in different morphological forms and may be caused by various agents. Besides the interstitial pneumonia found in various known viral, rickettsial, fungal, and protozoal diseases,1 and besides the syphilitic pneumonia alba, there are certain forms of unknown origin which may be differentiated on morphological or clinical grounds. This group includes the following conditions:The condition described by Hamman and Rich2 as acute diffuse interstitial fibrosis, characterized clinically by acute symptoms and histologically by fibroblastic invasion of the alveolar walls.The disease entity called eosinophilic pneumonia (Loeffler), characterized by focal infiltrations of the interstitial tissue with eosinophilic cells.The so-called acute interstitial pneumonitis or atypical pneumonia, which occurs mainly in adults.3A group of diseases, including the so-called plasma cell pneumonia, the virus pneumonia of infants, and the interstitielle Pneumonie der Frühgeburten, which are possibly identical and which occur mainly in infants.4

Thrombocytopoiesis was studied by direct, continuous observation in tissue cultures of bone marrows taken from three patients with chronic idiopathic thrombocytopenic purpura and from normals following the addition of a potent anti-platelet serum to the culture media. The process of platelet production was similar in these two conditions and followed the pattern observed in bone marrow cultures of healthy individuals. The breakdown of megakaryocytes of patients with idiopathic thrombocytopenic purpura and those treated with anti-platelet serum was greatly accelerated. No morphologic evidence of injury to the megakaryocytes was present. The platelets produced showed degenerative changes, they were agglutinated and underwent phagocytosis by the myeloid elements and reticulum cells were present in the cultures.

The results of therapeutic trials in fifty-six patients with severe nutritional megaloblastic anemia due to folate deficiency with varying parenteral doses of pteroylglutamic acid and leucovorin are described.

The study of maturation of rabbit reticulocytes in vivo revealed an essential correlation between the degree of reticulocytosis, the RNA content of the circulating red blood cells and their ability to carry out amino acid incorporation into protein. The nevertheless frequent occurrence of considerable quantitative discrepancies between these parameters during the progress of maturation appears to be attributable to fluctuations in the reticulocyte population due to intrinsic difference in the life span of these cells and to release of young reticulocytes from the hyperplastic bone marrow into the circulation. The distortions in the pattern of maturation kinetics by the continued contribution of the bone marrow seem to be largely eliminated by blocking erythropoiesis at the height of reticulocytosis with the aid of actinomycin D treatment.

The use of intravenously injected Cr51-tagged red blood cells in the quantitative determination of gastrointestinal blood loss has been described.