In vitro RNA synthesis of leukemic leukocytes (6 cases of acute myelogenous leukemia, each one case of lymphocytic and monocytic leukemia, and 1 case of acute exacerbation of chronic myelogenous leukemia) was apparently inhibited by adding 100 μg per ml of hydrocortisone to the incubation medium.
This inhibition of RNA synthesis in leukemic leukocytes by hydrocortisone was demonstrated to be caused by a decrease of chromatin RNA-polymerase activity in the cells preincubated with hydrocortisone.
Although the RNA synthesis of normal peripheral granulocytes, lymphocytes, normal bone marrow cells, chronic myelogenous leukemia cells was also inhibited by the addition of hydrocortisone, the degree of inhibition was far less than that observed in acute leukemia cells.
It is suggested that this difference in the sensitivity to hydrocortisone in vitro is caused by the difference of the turnover rate among these cells.
Relationship between the in vitro inhibitory effect and clinical effect of the hydrocortisone treatment is not clear.
However, it seems certain that the hydrocortisone exerts some cytotoxic effect on acute leukemia cells through its inhibition on RNA synthesis, although the degree of inhibition or clinical effect could be differed by each case.

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Intrinsic factor was assayed after stimulation with histalog in 92 patients with miscellaneous diseases, 11 healthy subjects and 18 patients with pernicious anemia.
The mean hourly output of intrinsic factor was 14,800±2,030 units in healthy subjects. In 22 cases where biopsy revealed superficial gastritis the output showed no significant difference from that of healthy controls, whereas 61 patients with atrophic gasritis secreted significantly less intrinsic factor than healthy controls. The decrease in the output of intrinsic factor appears to be related to the grade of gastritis, since there is no common abnormality causing such decrease among diseases under observation.
The mean hourly output of intrinsic factor in 18 achlorhydric patients with diseases other than pernicious anemia was 4,400±1,440 units which was significantly lower than the value in controls, indicating a correlation between acid and intrinsic factor secretion.
Cases were classified into 5 groups according to the output of intrinsic factor. In the group of the hourly output less than 5,000 units, a marked decrease in acid secretion was observed, and many achlorhydric cases were detected. Furthermore, the degree of changes such as glandular atrophy, decrease in the parietal cell mass and intestinalization tended to be high in patients in this group. These findings, although less severe than those seen in patients with pernicious anemia in relapse, resemble abnormalities in gastric functions as well as histological pictures of the stomach in cases with pernicious anemia where some improvements have been attained after administration of prednisolone.

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On admission to our hospital manifestations of 220 patients with acute leukemia (98 myelocytic, 68 monocytic and 54 lymphatic) who had not been treated with antileukemic agents, were statistically studied in order to define the category of atypical factors in acute leukemia which were used to be applied rather vaguely. Analyzing these factors the criterion of atypical leukemia have been set as follows: the percentage of blasts and promyelocytes or promonocytes (only blasts in cases of lymphatic leukemia) is less than 20% in the peripheral blood and less than 40% in the bone marrow. The number of cases which corresponded to this criterion were 9 myelocytic, 10 monocytic and 4 lymphatic.
The characteristic manifestations of atypical leukemia were (1) high incidenec in people, over the age of fifty, (2) mild initial symptoms, (3) leukopenia, low percentage of leukemic cells, reticulocytosis and frequent appearance of erythroblasts in the peripheral blood, (4) low percentage of leukemic cells, erythroid hyperplasia and hypocellularity in the bone marrow, and (5) prolonged survival time of cases.
From the clinical pictures of our atypical leukemic cases, it was suggested that there was close relationship between atypical leukemia and preleukemia manifested as aplastic anemia.

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Effect of cyclic maintenance therapy on the duration of complete remission and survival of acute leukemia is reported.
Cyclic maintenance therapy was composed of administration of one of the following drugs at one time for the period of 4 weeks: 6MP 2.5 mg/kg/day orally, cyclophosphamide 2.5 mg/kg/day orally, prednisolone 30 mg/day orally, methotrexate 2.5 to 5.0 mg/day orally or 10 to 15 mg twice a week orally, or cytosine arabinoside 40 to 200 mg twice a week intravenously. The maintenance therapy was instituted after complete remission was obtained with various remission induction treatment.
During the 5 year period for 1965 through 1969, 25 patients with acute leukemias (13 myeloblastic, 2 paramyeloblastic, 1 monocytic and 9 lymphocytic) were treated with cyclic use of drugs for their remission maintenance. Control groups consisted of 22 cases of 6 MP maintenance and 36 cases of non-maintenance; only those whose remissions lasted longer than 4 weeks were selected to match the cyclic maintenance group.
The median duration of complete remission for cyclic, 6 MP and non-maintenance groups was 11 1/3, 4 2/3 and 2 months, respectively. Differences between each of the 3 groups are statistically significant. The median survival for the 3 groups was, in the same order, 19, 10 1/3 and 8 1/3 months, respectively. The difference of survival time between cyclic and 6 MP maintenance groups is highly significant but that between 6 MP and non-maintenance groups is not significant. Namely, cyclic maintenance therapy attained the prolongation of survival of acute leukemia patients, which 6 MP maintenance therapy could not.
Side effects of cyclic maintenance therapy were minimal and easy controlable. No interruption of the therapy was necessary.
The marked life-prolonging effect of cyclic maintenance therapy also is well reflected in the analysis of a total of 94 acute leukemia cases treated in the same 5 year period. More than 10 per cent of the patients (12) survived longer than 2 years. The median survival is 5 1/3 versus 3 1/3 months for the 100 cases treated during the preceding 5 years. Twenty per cent survival was 14 2/3 versus 8 1/3 months.
Thus, cyclic maintenance therapy described here is practical and effective way of maintenance therapy of complete remission in acute leukemia.

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This is a case report of a 27 year old female patient who had an acute hepatitis, most likely of viral origin and subsequent hematological aplasia while she was convalescing from hepatitis. She had had two small dosages of chloramphenicol a few weeks and a month or so prior to the outset of hepatitis. Hepatitis was rather severe but she seemed to be recovering steadily. The entire course terminated in about 4 months after the onset of hepatitis, and in one and a half months after the first sign of pancytopenia.
It might be postulated that chloramphenicol had predisposed the marrow to irreversible damages induced by hepatitis virus.

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A case of twenty three years old female with hemorrhagic diathesis was diagnosed as von Willebrand's disease in 1967.
Bleeding time was 25 minutes, coagulation time, platelet counts and clot retraction were normal, and rate of platelet adhesiveness was 11%.
Factor VIII activity was elevated from 5% to 25% after an infusion of AHG concentrate (Cohn fraction I), although the logically expected value was estimated to be 14%.
After two and half years of her dismissal from the hospital, she complained of sudden severe abdominal pain and thereafter her vital signs were diminished markedly, and she died on the next day. At autopsy, there was 1000 ml of blood in the abdominal cavity, and some hematomas were found in the bilateral ovaries and retroperitoneal serosa.
The massive ovarial hemorrhage probably due to the ovulation seemed to be the direct cause of her death.

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The patient was a 13-year-old boy who was admitted because of fever, edema, cough, husky voice, generalized lymphadenopathy, hepatosplenomegaly and exanthema. Two months before the admission, he was noted the swelling of left axillar lymph node, which was removed and diagnosed as benign reticulosis histologically. His clinical signs mentioned above developed gradually during one and half months after the onset. On the admission, the laboratory examination revealed anemia, leukocytosis with abundant reticulum cell, hypocholesteremia, hypercupremia and dysproteinemia (increase of α₁- and α₂-globulin, decrease of Ig M). Against the administration of antibiotics and prednisolone, he was died of marked dyspnea apparently due to the infiltration of malignant reticulum cells on the tracheal mucosa.

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There have been many discussions of the interrelationship between aplastic anemia and leukemia. In view of this, a brief report seems warranted.
Case: A 57-year-old male with no signs or complaints, was admitted to this hospital for health examination in February, 1968. Hematological examinations showed slight pancytopenia and mild hypoplastic bone marrow. He was treated as hypoplastic anemia for about 7 months since that time in our hematology OPD, working as usual until the second admission in November, 1969, when he was diagnosed as acute leukemia because of fever, skin involvement and the appearance of atypical immature cells in the blood and bone marrow. He suddenly died on the 9th hospital day of bilateral leukemic pneumopathy with marked hemorrhage.
Autopsy revealed leukemic infiltrations in the bone marrow and other organs. Infiltrating cells had some similarity to reticulum cells, having marked cytoplasmic deformity and irregular pseudopods. The majority of the cells showed negative peroxydase and PAS reactions, and positive SDH reaction.
On electron microscopic investigation, free ribosomes were found only sparsely, and the endoplasmic reticulums were rare. The mitochondriae predominantly situated in the nuclear indentation. The Golgi-apparatus were well developed.
Examinations on the first admission had shown various coagulation abnormalities, i.e. prolonged bleeding time and heparin clotting time, decreased plasma prothrombin value, and increased serum prothrombin value. These abnormal coagulabilities might be a good reflection of the preleukemic state. A review of the bone marrow specimen obtained 20 months before his death revealed immature “cell nests” suggestive of developing leukemia in some part of hypoplastic bone marrow.

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