1. Weight loss, progressive anemia, and a moderate increase in reticulated red blood cells occurred in seventeen guinea pigs on a diet deficient in vitamin C. 2. The histological changes of the bone marrow removed from guinea pigs with scurvy showed large numbers of erythrogenic cells, but scant evidence of active maturation to the adult erythrocyte. 3. A reticulocyte response was induced in guinea pigs with scurvy when fed orange juice daily. 4. The histological changes of the bone marrow removed from guinea pigs during the reticulocyte response showed large numbers of mitotic figures and relatively more adult red blood cells than in the bone marrow from guinea pigs with scurvy that had not been treated with orange juice. 5. It is concluded from this study that the anemia of experimentally induced scurvy in the guinea pig is largely dependent upon vitamin C deficiency resulting in retarded maturation of the red blood cell.
1. A method has been described for the determination of the catheptic activity of leukocytes. 2. The catheptic activity of the leukocytes of normal and leukemic individuals has been investigated. 3. The leukocytes from all cases of untreated lymphatic leukemia, either chronic or acute, show lower catheptic activity than the leukocytes from any of the untreated myelogenous leukemias, either chronic or acute; the values for normal cases ranged between these two classes with much overlap. See PDF for Table 4. The lymphocyte fractions separated from the blood of normal subjects possess essentially the same catheptic activity as the total unfractionated leukocyte populations. 5. An attempt to isolate granulocytes from the blood of normal subjects for separate analysis was not successful.
The effect of pH on the catheptic activity of leukocytes from normal, polycythemic and leukemic (lymphatic, myelogenous, eosinophilic) blood has been investigated. When acid‐denatured hemoglobin was used as the substrate, the leukocytic cathepsins from polycythemia and myelogenous and eosinophilic leukemia were more active than normal. All showed optima at pH 3.5 except polycythemia, which was pH 4.0. When urea‐alkali‐denatured hemoglobin was used as substrate, the leukocytic cathepsins of polycythemia were more active than normal; of myelogenous leukemia, slightly less than normal; of eosinophilic leukemia, even less than normal; of lymphatic leukemia, exceedingly less than normal. All optima were around pH 8.5. When lymphocytes and granulocytes were separated from normal blood, the lymphocytes showed more activity than the granulocytes at pH 3.5 and less than granulocytes at pH 8.5. These observations indicate that the differences noted in the catheptic activities of cells as isolated from various leukemias are not due to a preponderance of one type of cell but rather to inherent deranged chemical properties of the cells.
There is no obvious reason for supposing that chronic myelogenous leukemia is a dietary deficiency disease. Dietary inadequacy or abnormalities of the gastrointestinal tract, almost invariably present in the deficiency group of anemias including pernicious anemia, apparently rarely occur in chronic myelogenous leukemia. On the other hand, the abnormal proliferation of primitive white blood cells in the bone marrow of myelogenous leukemia might conceivably have a physiological analogy in the maturation arrest of the primitive red blood cells crowding the bone marrow of pernicious anemia in relapse. Although gastric anacidity is only occasionally present in myelogenous leukemia, the simultaneous advent of 2 patients with chronic myelogenous leukemia, one of whom was in a leukopenic phase and both of whom had gastric achlorhydria, provided the stimulus for performing the observations described MOW.An attempt was first made to supplant an entirely hypothetical defect of the gastrointestinal secretions of the 2 patients by administering alone, or in combination with other tissues, preparations of certain organs known to be effective in pernicious anemia. The daily intramuscular injection for 20 days of liver extract 343 N.N.R., derived from 25 gm. of liver, in each of the 2 patients mentioned above, was without effect. Next, the daily administration for 20 days of combined desiccated preparations derived from 100 gm. of gastric mucosa, from 250 gm. of the mucosa of the small intestine, and from 50 gm. of the pancreas of the hog, respectively, was carried out. In one of these patients the daily administration for 11 days of about 150 gm. of the mixed fresh tissue (except for the head, skin, and extremities) of newborn rabbits was then instituted in an attempt to supply a "shotgun" preparation of normal animal tissues and their metabolic products. All of these procedures were entirely without effect upon the clinical and hematological features of the disease. Similar negative results were obtained by * The expenses of the present investigation were borne in part by grants from the J. K. Lilly gift to the Medical Sehool of Harvard University.
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