Serum lysozyme activity of patients with various types of leukemia in children by lysoplate method was measured. All patients with monocytic leukemia and some patients with chronic myelocytic leukemia were found to have highly elevated activity of serum lysozyme in active stage of illness. On the other hand, patients with acute lymphocytic or acute myeloblastic leukemia showed rather lower lysozyme activity than normal control. However, the lysozyme activity in monocytic leukemia was not always high at the late stage after repeated relapses and this was different from change of LDH activity in the course of acute leukemia. This phenomenon may suggest that the long standing, intensive chemotherapy results in modification of the nature of blast cell. The present study revealed that determination of serum lysozyme was very useful for specific diagnosis and an indicator of therapeutic effectiveness of acute monocytic leukemia in children.

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A 62-years-old male patient with leukemic reticulum cell sarcoma complicated by Hashimoto's thyroiditis was reported. The patient admitted on February 3, 1973, because of a mild bulging in the left upper quadrant of the back accompanied by left lateral chest pain. Three years prior to admission a diagnosis of struma simplex was made. On admission neither hepatosplenomegaly nor enlargement of superficial lymph nodes were noted. Roentogenogram of the chest, however, revealed abnormal shadows in the right upper mediastinum and along the left paravertebral area. Laboratory studies during the course showed a diffuse hypergammaglobulinemia with anti-thyroglobulin antibody (titer 1:409,600) and eosinophilia up to 32%. Scintigrams showed a diffuse concentration of I¹³¹ at the site of goiter, and also a dense uptake of Ga⁶⁷ in the left mediastinum extending over the left diaphragm. On May 28, a sudden episode of high fever, dyspnoea and severe chest pain was recorded. Chest X-ray showed left pleural effusion.
Cytologic examinations of the fluid disclosed numerous malignant cells characteristic of reticulum cell sarcoma. Although combined chemotherapy was performed, the patient succumbed to the leukemic condition and passed away on July 14, 1973, due directly to hemopneumothorax and septicemia arising from staphylococci.
The postmortem examinations showed Hashimoto's thyroiditis and reticulum cell sarcoma, of a histiocytic type, which appeared to develop from the upper mediastinal region. Histologic findings of invasions of tumor cells into the lymphoid tissues suggested extranodal origin.
This case was considered to be very rare with respect to features of tumor-progression and clinical course of reticulum cell sarcoma and very interesting from a point of view of immunological abnormalities in autoimmune diseases which might have preceded the development of malignant lymphoma.

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Two cases of Infantile Genetic Agranulocytosis in a family are reported.
In family history, parents were first cousins.
Case 1: A 11 month-old female was admitted because of fever and respiratory distress.
On physical examination, furunculosis was observed on the neck. Bilateral pulmonary respiratory sounds were diminished.
The hematologic studies revealed agranulocytosis and monocytosis. Bone marrow showed maturation arrest of neutrophilic granulocytes and monocytosis containing vacuoles in the cytoplasm.
Case 2: A 7 month-old female was admitted because of recurrent otitis media and furunculosis since 5 months ago.
On phisical examination, furunculosis was noted on the neck and head.
The hematologic studies and bone marrow findings revealed the same as case 1. The total serum protein level was 7.9 g/dl and serum electrophoresis showed hypergammaglobulinemia. Local inflammatory response (Skin Window Technique) was hypocellular with mononuclear cell infiltration 10 hours after the abrasion.

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This report is concerned with a familial occurrence of aplastic anemia seen in the father and his son. The family history also included anaphylactoid purpura in a grandchild.
Case 1. A 63 year old father was admitted in July, 1973, because of gingival bleeding. Pancytopenia and hypoplasia of the bone marrow were pronounced. He died after 1.5 months despite intensive corticosteroid therapy.
Case 2. A 43 year old son of Case 1 was admitted in January, 1974, because of gingival bleeding. He responded favorably to corticosteroid and fluoxymesteron and has since been doing well.
Case 3. A 9 year grandson entered the hospital in May, 1964, because of abdominal pain and purpura of the lower extremities. A diagnosis of anaphylactoid purpura was made and he was discharged 1 month later.
For the elucidation of the etiology of aplastic anemia which is not yet known, extrinsic factors as well as intrinsic factors are to be considered. These three patients had been engaged in farming and there was exposure to insecticides. In search of an intrinsic factor, we carried out hematological examination on the family members, but failed to demonstrate any abnormalities. The chromosome analysis of Case 2 and 3 disclosed no significant aberrations. It is felt that more vigorous effort be made to demonstrate intrinsic factors in patients with acquired aplastic anemia, since there are many reports on familial occurrence of congenital aplastic anemia.

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Two siblings with hereditary refractory sideroblastic anemia were described. The propositus, 20-year-old male, had been noticed of pale face since 9 years of age. He was admitted to the Chukyo Hospital in Oct. 1973, with complaints of exertional dyspnea and general fatigue. Marked hypochromic anemia with peripheral red blood cell count of 3.33 millions and hemoglobin level of 4.8 g/dl showing apparent dimorphism of red cells were found by laboratory examination. Leukocyte and platelet counts were within normal limits. A bone marrow examination showed erythroid hyperplasia with 38% ringed sideroblasts.
Serum iron was as high as 226 μg/dl and unsaturated iron binding capacity was 30 μg/dl. Ferrokinetic study revealed rapid plasma iron disappearance with reduced red cell utilization, a pattern of ineffective erythropoiesis. A liver biopsy disclosed marked iron deposition. The patient responded partially to pyridoxine with an increase of red cell count up to 5.1 millions and hemoglobin level to 8.2 g/dl, but without further improvement by continued pyridoxine administration.
An elder brother of the propositus showed moderate hypochiomic anemia with increased ringed sideroblasts in the bone marrow.
Based on the results that activities of δ-aminolevulinic acid synthetase of marrow erythroblasts of the propositus and of the elder brother were markedly and moderately reduced, respectively, the significance of the enzyme defect in the pathogenesis of hereditary sideroblastic anemia was suggested.

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Erythroid aplasia following the administration of drugs may be due to various mechanisms. Although the pathogenetic mechanisms involeved in drugs remain incompletely understood, a great deal of light has been shed on this problem by in vitro bone marrow cultures.
We have experienced three patients who suffered from erythroid aplasia associated with exposure to thiamphenicol, diphenylhydantoin and thiopental, respectively. These patients recovered rapidly when the offending agents were removed.
To determine the causative drug in three patients, in vitro heme synthesis and colony formation were undertaken with the addition of the drugs to the culture systems.
Thiamphenicol (10 μg/ml/plate) produced to inhibit heme synthesis in the bone marrow culture of a patient who had recovered from thiamphenicol-induced erythroid aplasia. Inhibition of in vitro heme synthesis was greater with his own serum than with fetal calf serum. However, the failure of thiamphenicol to inhibit granuloid colony formation was observed. These data suggest that some immune mechanisms with the fall in ferrochelatase activity may induce erythroid aplasia by thiamphenicol.
The specific inhibitory effect of diphenylhydantoin (20 μg/ml/plate) on in vitro heme synthesis did not occur in the bone marrow from a patient who recovered from diphenylhydantoin-induced erythroid aplasia.
Thiopental (15 μ/g/ml/plate) did affect the significant reduction of the cell viability in bone marrow cell suspensions from a patient recovered from erythroid aplasia. Her immunoglobulin G was elavated and the skin reaction test with thiopental also gave positive. These data strongly suggest that some immune mechanism may take part in causing erythroid aplasia.

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1. The medical records of 71 cases of malignant lymphoma examined at the Department of Hematology, Nagasaki Univercity School of Medicine during the 3-year-period from April 1972 to May 1975 were reviewed for data on serum calcium, phosphorus and white blood cell count. High serum calcium level were found in 20 cases. Of these 13 patients (7 cases of reticulum cell sarcoma and 6 cases of lymphosarcoma) were of leukemic type, more than 20% of white blood cells being abnormal. All the 13 patients died within 6 months after hospitalization.
2. Five autopsied cases of leukemic malignant lymphomas with hypercalcemia are described. They all died in 40 to 180 days after hospitalization. At autopsy 4 cases were diagnosed as reticulum cell sarcoma and one as lymphosarcoma. Electron microscopic findings of the tumor cells in the blood of lymphosarcoma apparently revealed characteristics of lymphatic cells, while those of reticulum cell sarcoma failed to show findings enough to elucidate the origin of the cells, although they were different from lymphatic cells. There were no fine structures in these cells to suggest parathormone excretion.

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A four-month-old girl with autoimmune hemolytic anemia (AIHA) is described. According to our knowledge, this is the first case of AIHA with anti-D specificity in Japanese and she is the youngest among the AIHA. previously reported in Japan.
In this patient, the administration of corticosteroid was effective to reduce the reticulocyte counts and rise the hemoglobin levels. Transfusion using Rh negative washed red blood cells had a favourable effect on increasing her hemoglobin concentrations, when she suffered from hemolytic crisis which was thought to be induced by infection.
The patient died of pneumonia and autopsy findings showed marked atrophy of adrenal grands and thymus, erythroid hyperplasia in bone marrow and pneumonia caused by Pneumocystis carinii.

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75-year-old man of atypical leukemia was reported. After removal of the bladder tumor (transitional cell carcinoma, grade I), 22 intravesical instillations of thio-Tepa were used for about 2 years just before his death. Following the third instillation, leukopenia and anemia were pointed out. Myeloblasts (21%) were appeared in peripheral blood 2 weeks before his death. On necropsy, bone marrow showed marked proliferation of all series of bone marrow cells, but maturation arrest was clear in granulocytic series. Infiltration of myeloblast-like cells was found in the liver, spleen and lymph nodes. The possibility that thio-Tepa may have modified clinical course and autopsy findings of this case was discussed.

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The incidence of granulocytopenia in association with anti-thyroid drugs has been studied. Of 78 patients treated with methimazole for the past six years, 7 cases developed neutropenia of less than 1,000/mm³. Decrease in neutrophil count more than 2,000/mm³ comparing to the values before the therapy was noted in 20.5% of the cases during the administration of the drug. Though most of the episodes of neutropenia were transient and reversible, one case developed classical symptoms of agranulocytosis.
Occurrence of neutropenia induced by methimazole is related to the duration of the therapy and seems to be dose-dependent. Therefore, frequent routine blood cell counts may be necessary for the early detection of leukopenia and prevention of agranulocytosis during anti-thyroid medication.

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A Japanese family with G-6-PD deficiency was reported. The propositus was an 8-year-old boy who was referred to our outpatient clinic because of fever and black urine after having taken prifinium bromide, methylscopolamine and chloramphenicol for abdominal pain. On physical examination nothing was remarkable except for frank anemia. Laboratory examinations revealed RBC 195×10⁴/μl, Hb 5.7 g/dl, Ht 19%, reticulocyte 17.1%, platelet 35×10⁴/μl and WBC 16,700/μl with normal differentials. Haptoglobin was markedly depressed and Coombs' test, cold agglutinin titer and complements 3 and 4 were all within the normal limits. Abnormal or unstable hemoglobin was not detected. G-6-PD activity was almost zero associated with abnormal GSH, glutathion stability test and Heinz body formation test.
From the foregoing findings, the diagnosis of G-6-PD deficiency was established. Further studies of his family members revealed two other affected males and four heterozygous females. Cases of G-6-PD so far reported in Japan have been reviewed with reference to clinical manifestations and trigger drugs. Further investigations to characterize this variant are in progress.

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