Henry Borsook

Differential immune lysis of erythroblasts.

WE have investigated the stage in erythroblast maturation at which erythrocyte membrane antigens first appear, using an antiserum which lysed rabbit erythrocytes. Mature acidophilic erythroblasts were lysed with a lower concentration of antiserum (complement in excess) than were the less mature basophilic cells.

A DISCUSSION OF HUMORAL ERYTHROPOIETIC FACTORS

I propose to discuss the evidence for the existence of specific humoral erythropoietic factors, with some attention to the question of whether there may be more than one such factor; the matter of producing a potent extract from the blood ; and some physical and chemical properties of preparations with erythropoietic activity. To facilitate this discussion, I shall designate the erythropoietic material in plasma as E P and that in urine as EU. EP and EU may or may not be the same; there may be more than one EP or EU. I t will help to eliminate some of the disagreement in the literature if we accept the following working hypothesis. The responses to increasing potency of EP or EU appear in the foliowing order: increased red cell activity in the bone marrow, reticulocytosis, increased uptake of FeK9 in the blood by an increase of newly formed red cells, increased red cell volume, hematocrit, red cell count, and hemoglobin. Only powerful stimulation can provoke a true polycythemia in the 10 days to 2 weeks of the usual experiment; then all the signs of increased erythropoiesis are present. I t does not follow, and it is not the case, that a preparation causing a reticulocytosis or even an increased uptake of Fe6g will also induce polycythemia. Herein lies much of the contradiction in the literature. It may be that there are several physiological erythropoietic factors and that the attack of some of these is more deep-seated than others, that is, some may cause only a reticulocytosis, and the resulting increased red cell formation is too slow and too small to be noticed except by tracer methods such as Fe59. Also, it may be that there is but one erythropoietic factor; it can stimulate a true polycythemia if a sufficiently large dose is used, but a preparation of low potency may cause only a reticulocytosis or small increase in uptake of FeSg. Elsewhere in this monograph, Hodgson presents data showing that the relation of the response to dose is logarithmic. This would be sufficient to account for the difficulty of producing a polycythemia with the plasma after hemorrhage or phlebotomy, because the usual anemia after hemorrhage elicits only a moderate increase in EP (see below). The modern era begins with the often quoted paper by Carnot and Deflandre.7 In a typical experiment these investigators withdrew 30 ml. of blood from a rabbit, bled the animal again on the next day, and injected 9 mi. of the serum of that blood into a normal rabbit, whose red cell count rose 24 hours later from 5.5 million to 8 million/cu. mm. They called the substance in the anemic serum that induces the polycythemia hemopoietin.

Question of Purity of Erythropoietic Factor Concentrates.

Summary The bulk of erythropoietic activity of anemic plasma can be concentrated in a fraction which represents less than 0.5% of plasma proteins. Yet from the similarity in yield and electrophoretic behavior of the corresponding inactive fraction from normal plasma, it appears likely that the erythropoietic factor constitutes only a small portion of the present concentrates.

Studies on erythropoiesis: III. Different patterns of protein and hemoglobin synthesis before and after terminal differentiation in adult rabbit marrow☆

Abstract Six Chromatographic fractions of hemoglobin were found in the erythrocytes of adult rabbits. The hemoglobin synthesized in the pre-differentiation (early) erythroblasts is mainly that of an acid minor; in the post-differentiation erythroid cells (intermediate and terminal erythroblasts and reticulocytes) it is mainly the hemoglobin major. In the pre-differentiation cells the lesser proportion of the protein synthesized is hemoglobin; in the post-differentiation cells it is preponderantly hemoglobin. Actinomycin D does not affect the pattern of protein and hemoglobin synthesis in either the pre- or post-differentiation compartments of cells; it blocks the change from one to the other, i.e., from the basophilic to the polychromatic stages with the attendant disappearance of cytoplasmic basophilia and diversion of protein synthesis to preponderantly that of the hemoglobin major. The differentiation is a terminal one: DNA and RNA synthesis declines and eventually stops, and DNA and RNA disappear largely, as do many nonhemoglobin proteins; hemoglobin synthesis after the differentiation increases rapidly and eventually stops. Because hemoglobin does not turn over, it becomes the preponderant constituent of the cell. These changes are analogous to those in the maturation of the lens.

The Relation of the Vitamin B6 Human Requirement to the Amount in the Diet

Publisher Summary This chapter provides the observational and experimental data on the estimation of vitamin B 6 requirement of infants and young adults and discusses the effect of age on the amounts of vitamin B 6 and some other vitamins in the tissues. The chapter describes the amount of vitamin B 6 in representative American diets. One of the ways in which the B 6 requirement has been estimated was based on the energy requirement or expenditure. An estimate of the B 6 requirement needs to be informed by data from two sources: (1) from tests based on intermediary metabolism and (2) on the extent of individual variation in the B 6 requirement by a number of different tests. Surveys of infant diets in the United States indicate that the great majority provide more than 0.3 mg daily. The factor of age needs to be taken into account. There is a strong case for increasing the B 6 in the food supply. The B 6 requirement does not depend on the calorie production or requirement and with the recommendation for people to eat less the number with unsatisfactory B 6 intake will increase unless the food is made to contain more B 6 .

Nutritional Status of Aircraft Workers in Southern California: III. Effects of Vitamin Supplementation on Absenteeism, Turnover, and Personnel Ratings

1This Study of the nutrition of aircraft workers in California was sponsored by the Nutrition Committee (R. A. Millikan, Chairman), appointed by the Board of Supervisors of the County of Los Angeles, California, and the Committee on the Nutrition of Industrial Workers of the National Research Council. The Study was supported in part by the sponsors and by the following: the California Institute of Technology, The Lockheed Aircraft Corporation, the Milbank Memorial Fund, the War Production Board, and the Works Projects Administration (Project No. 12372). Support was also received from the California Fruit Growers Exchange, the Gelatin Products Corporation, Merck and Company, the National Oil Products Company, the Research Corporation, E. R. Squibb and Sons, and the Vita-Food Corporation. We wish to thank the officials of the Lockheed Aircraft Corporation who authorized the Study and who offered us every facility to carry it out. Their contribution was especially noteworthy in that the Study was made during the years of rapid expansion (1942-1943), under the heavy stress such activity implies. We are greatly indebted especially to Mr. Robert E. Gross, President; Dr. F. E. Poole, Medical Director, to whose department this Study was assigned; Mr. Dwight L. Palmer, Manager, Industrial Relations Research Division; Mr. L. Stockford, Analyst, who participated in the collection of data and in the preparation of preliminary reports; and to Mr. R. B. Robertson, Assistant Director of Industrial Relations. It is a pleasure to record the patient friendliness and cooperation extended us by the personnel of the divisions of Active Files and Inactive Files, and by the supervisorial staff in the plant. We wish to thank the local union (affiliated with the A. F. of L.), to which the workers belonged, for its approval of the Study and for its cooperation. We are indebted to Miss Dorothy G. Wiehl of the Milbank Memorial Fund for her searching criticism of the data in this report, for many valuable suggestions on the mode of presentation and assistance in the statistical analysis. We are indebted also to Miss Josephine Williams of the California Institute of Technology for her zeal and thoroughness in running down innumerable details in the Company records, and for her participation in the task of rechecking and tabulating all the data. We take this occasion, also, to thank Dr. Roger Stanton of the California Institute of Technology, who assisted us, as a volunteer, in every phase of the Study. 2 California Institute of Technology, Pasadena.

Nutritional Status of Aircraft Workers in Southern California. V. A Conspectus of the Survey and Its Field

T 1 HIS is the concluding paper on the Study of the Nutritional Status of Aircraft Workers in Southern California. It is a summary of the whole Study and discusses the results in the context of related studies and their objectives. The immediate impetus to the undertaking of the Study came from the call for maximum production in the war effort. In the years preceding the National Emergency and the War the general public had become increasingly interested in nutrition, especially in the question of the value of vitamin supplements. A few employers were convinced that production was improved by improving the nutrition of their workers. In most cases this opinion was an interpretation of the results of tests, without controls, of supplementing the diets of workers with vitamin concentrates. There were no adequate studies of the nutritional status of the workers before and after a vitamin supplement was used, nor of precisely what was gained by its use. In most industrial groups in the United States there is probably relatively little severe or acute nutritional deficiency. At the time of the declaration of the National Emergency in I941 the effects of improving the diet of such a population on health, working calThe Study of the nutrition of aircraft workers in California was sponsored by the Nutrition Committee (R. A. Millikan, Chairman), appointed by the Board of Supervisors of the County of Los Angeles, California, and the Committee on the Nutrition of Industrial Workers of the National Research Council. The Study was supported in part by the sponsors and by the following: the California Institute of Technology, The Lockheed Aircraft Corporation, the Milbank Memorial Fund, the War Production Board, and the Work Projects Administration (Project No. 12372). Support was also received from the California Fruit Growers Exchange, the Gelatin Products Corporation, Hoffman-LaRoche, Inc., Merck and Company, the National Oil Products Company, the Research Corporation, E. R. Squibb and Sons, and the Vita-Food Corporation. s California Institute of Technology, Pasadena. 8 Milbank Memorial Fund, New York.

Effect of Added Purines on Uric Acid Production by Isolated Tissues of the Rat

The effect of added purines on uric acid production by the kidney, liver, diaphragm, spleen, intestinal mucosa, and smooth muscle of the intestine of the rat was investigated by the methods previously described. 1 The results (Table I) indicate that the intestinal mucosa and the liver account for most of the uric acid production from these purines. The mucosa is the only tissue that acts upon adenine to any extent. It is also very active in transforming guanine, xanthine, and hypoxanthine into uric acid. The liver actively transforms all these purines except adenine. Striated muscle (diaphragm) has very little effect upon any of them, and the small conversion due to smooth muscle may be the action of small quantities of mucosa which could not be removed. The kidney and spleen were only moderately active in the conversion of xanthine and hypoxanthine. The study of the production of uric acid in these tissues from other possible precursors is being studied further.