δ-aminolevulinic acid (ALA) synthetase activity in erythroblasts has been measured by the new method developed in our laboratory in 5 patients with sideroblastic anemia. These patients were admitted in the Tokyo University Hospital, Nagoya University Hospital, Okayama University Hospital, and Toranomon Hospital. Diagnosis of the sideroblastic anemia had been established in these hospitals. The ALA-synthetase activity was markedly reduced to almost deficient level in one case, moderately decreased in 2 cases, and normal in 2 cases. In the case with markedly decreased ALA-synthetase activity, incorporation of ¹⁴C-glycine into heme in erythroblasts was also markedly reduced. Decrease in hemesynthetase activity in erythroblasts of this case, however, was slight as compared to the decrease in ALA-synthetase activity. The authors believe that this is the first case of sideroblastic anemia with proven deficiency of ALA-synthetase activity.

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Platelet transfusions are effective in the control of hemorrhages in thrombocytopenic patients with acute leukemia. They are especially valuable as a supportive measure during intensive chemotherapy.
The need for exceedingly large amounts of blood and the possibility of immune reactions to multiple platelet transfusion are thought to be major obstacle in the routine use of platelet transfusion.
Highly concentrated platelet rich plasma from ACD treated blood was obtained from a patient with thrombocythemia by means of closed system of plastic bags. Five patients with acute leukemia who had marked thrombocytopenia and severe hemorrhagic manifestation were given concentrated platelets in dose ranging from 4.2 to 21.7×10¹¹/m².
Espistaxis, gingival bleeding and melena were arrested following administration of fresh platelet in all of 5 patients, associated with increased platelet levels up to 30,000 platelet/cu mm. or more.
Availability and usefulness of large amounts of platelet from such donor as a patient with thrombocythemia will permit the administration of intensive chemotherapeutic agents in amounts many times greater than the conventional dose.

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New human cell lines from 4 patients were established. One derived from normal female, 2 from patients with chronic granulocytic leukemia whose bone marrow cells had Philadelphia chromosome, and one from a patient with XY/XXY mosaic of Klinefelter syndrome.
Chromosome constitutions of these cell lines were 46, XX in normal and chronic granulocytic leukemia and 47, XXY in mosaic of Klinefelter syndrome.
Morphological and functional characteristics of cell lines were discussed and usefullness of cell lines in hematological study was stressed.

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Hematological investigations, including erythrokinetic analysis, were carried out on 16 female and 3 male patients with hyperthyroidism, admitted to our department during the last 7 years. Results obtained were as follows:
1. Eleven out of these thyrotoxic patients, were slightly or moderately anemic, and in 8 cases with anemia their MCH level was less than 25 μμg.
2. Serum iron levels were lowered in 6 cases among 10 anemic patients, and UIBC were increased in all of 5 cases subjected to determination. Ferrokinetic study, carried out in 7 anemic cases, revealed a shortened PID with norma 1% RCU. Although values of both PIT and RCIT were normal or slightly high in all these cases, mean values of daily Hb production calculated from the data obtained erythrocyte survival study were decreased in 6 cases with anemia under hematologically steady state.
3. Apparent half survival time of erythrocytes in thyrotoxic patients ranged from 17.4 to 31.4 days.
4. Except for a few cases, iron treatment was required in most of cases with hypochromic anemia after the antithyroid therapy. In some of these cases, oral iron preparations given during hyperthyroid state could not raise their Hb level.
From these results it is concluded that anemia was frequently complicated with thyrotoxicosis and that the main cause of anemia seemed to be iron deficiency. Peroral iron treatment was effective only after improvement of thyrotoxicosis in many of anemic patients with iron deficiency. It is suggested, however, that other types of anemia than iron deficiency were occasionally observed in thyrotoxic patients. Further study is required to elucidate the cause of these types of anemia.

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Three patients of preleukemia were cytologically and cytogenetically studied. Case 1 was 38-year-old man with atypical myeloproliferative disorder. Most of his marrow cells contained 45 chromosomes with missing of Y chromosome. Thirteen months later he terminated in typical acute myelocytic leukemia. Case 2 was 50-year-old man with acquired sideroblastic anemia. Most of his marrow cells contained 47 chromosomes with one missing from group B and two different marker chromosomes belonging to E group. Ten months later he died of hepatic coma, when his blood pictures suggested acute myelocytic leukemia or erythroleukemia. Case 3 was 43-year-old man with pulmonary tuberculosis and suspected myelofibrosis. 100% of his marrow cells contained 47 chromosomes with an extra C group chromosome. Seven months later he died of miliary tuberculosis. Autopsy revealed myelocytic leukemia (chronic?) in addition to milliary tuberculosis.
Each case at preleukemic stage showed some hematological abnormalities in three blood cell lines (erythroid, granulocytic, thrombocytic) frequently observed in erythroleukemia or acute myelocytic leukemia. Evidence is presented that chromosome abnormalities may be common in both the erythrocytic and granulocytic precursors, and, for case 2, even also in megakaryocytes.
From these findings mechanism of leukemic transformation in our cases was discussed.

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The present report deals with treatment of polycythemia vera with Procarbazine (Prokarbazin, 1-methyl-2-p-iso-propylcarbamoyl-benzylhydrazine-hydrochloride) and particularly with effects of this drug on the hematocrit, remission rate and duration of remission.
Three of six patients were treated in 2 courses, and the other in 1 course. The hemoglobin level, red cell count, hematocrit, leukocyte and platelet count were measured immediately before and after procarbazine administration.
The average total dose given in 1 course was 8,560 mg (4,600 to 10,000 mg), and the average duration of treatment was 9.4 weeks (4-1/2 to 10-1/2). Leukocyte count was the main criterion for instituting and discontinuing treatment and in contrast to the series with Myleran, considerable reduction of leukocytes, platelets and red cells were observed in the cases treated with Procarbazine.
On the other hand, the fall in leukocyte alkaline phosphatase activities on discontinuation of treatment was observed in the present series. The complete remission was obtained in all patients, but the relapse occurred in 2. In this group the duration of remission was from 10 to 20 months or longer (av. 14 months and more) at the present time.
Although the evaluation of Procarbazine in the treatment of polycythemia vera remains to be determined, this drug appears to be the treatment of choice for control in polycythemia vera.

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This study has been undertaken to demonstrate the correlation between the proliferation of cancer cells and the increase of fibrinogen and its derivative proteins in the body fluids.
The concentration of plasma fibrinogen in patients having cancer increased in parallel with the growth of cancer and markedly decreased after surgical extirpation of tumor tissues.
Fibrinogen level in pleural and ascitic fluids was estimated by use of the single radial immunodiffusion method. The mean value of fibrinogen for 27 cancer cell-positive fluids was 160 mg/dl, compared to 51 mg/dl of 29 negative samples.
The immunoelectrophoresis, used for characterization of fibrinogen and detection of fibrinogen degradation products, was performed with the specific anti-human fibrinogen antiserum. The reaction patterns have been classified into five types and their relation to morphological characteristics of cellular components in the fluids has been investigated. The cancerous fluids were involved in Type IV and V which revealed two distinct lines closer to the cathode. Most of inflammatory effusions belonged to Type III and the transudates caused by liver cirrhosis or other diseases to Type I or II, forming very weak patterns.
It may be assumed that the estimation and immunological analysis of fibrinogen and its derivatives in the body fluids is useful for the diagnosis or differentiation of cancerous and other disorders.

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The inhibiting activity on blood coagulation by a new synthetic substance having a chemical structure of 4-(2-carboxyethyl) phenyl-trans-4-aminomethyl cyclohexane carboxylate hydrochloride was studied in vitro. The results obtained were as follows:
1. The substance exerted a highly potent inhibiting activity on thrombin. The kinetic study by employing the technique of Lineweaver and Burk revealed that the inhibition was competitive in fashion.
2. In addition, the substance inhibited either or both of process of the first phase of blood coagulation in which factor IX_a→IX and IX_a (factor VIII, phospholipid and calcium ions)→X interactions were involved.

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H. T., a male officer born on January 1, 1928, was first seen at the Tokyo University Hospital on July 23, 1956, because of lassitude and exertional dyspnea. His hemoglobin was 63%, RBC 3,740,000, WBC 1,300 with relative lymphocytosis and thrombocytes 22,000 per cu. mm. Examination of aspirated sternal marrow revealed an aplastic marrow with increase in the tissue basophils, plasma cells and reticulum cells. In October 1956 his hemoglobin dropped to 46% and he was first admitted on October 8, 1956. Therapy with cortisone and blood transfusion under the diagnosis of aplastic anemia produced a remission and he left the hospital on December 22, 1956.
He had been free from symptoms until December 1968, when the gingival bleeding was noticed and therapy with prednisolone was started.
He was again admitted on April 5, 1969, because of bleeding tendency. Blood examination revealed no anemia, but WBC was 24,100 with 3.0% myeloblasts and platelet count 7,600 per cu. mm. Sternal and iliac marrow aspirate revealed myeloid hyperplasia with marked decrease in megakaryocytes. Ph¹ chromosome was negative. Leukocyte alkaline phosphatase score was low. Spleen weight estimated by MHP was 130 Gm. Acute myeloblastic leukemia was strongly suspected and he was on a small dose of prednisolone. He was discharged on May 20, 1969.
The third admission was on July 11, 1969, with complaints of fever and precordial discomfort. Myeloblasts gradually increased both in the blood and in the marrow, and a diagnosis of acute myeloblastic leukemia was made. Anemia progressed and in the middle of February, 1970, miliary shadow was noticed on a chest X-ray film; antituberculous therapy was effective. After April 1970 oliguria progressed and he expired on June 15, 1970.
Autopsy revealed the diffuse proliferation of myeloid cells, especially immature form in the all bone marrow specimens examined. Erythroblasts and megakaryocytes were very few. Leukemic infiltration was noted in spleen, liver, lymph nodes and lungs. Miliary tubercles were seen in lymph nodes and lungs. The cause of oliguria was the obstruction of the ureters by the clotted blood from the hemorrhagic pyelitis.

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A 17-year-old boy with congenital deafness, growth and mental retardation was first seen because of pallor, anorexia and general malaise. Blood examination showed a marked pancytopenia and his neutrophiles had pseudo-Pelger anomaly. Bone marrow smears showed a remarkable hyperplasia of erythroid series, in which megaloblastoid, bi-or tri-nuclear cells and abnormal sideroblasts were observed. Neutrophilic promyelocytes had fine and scanty granules, and platelets production of megakaryocytes was almost negative. Treatment with corticosteroid hormone, folic acid, VB-12 and blood transfusion were not effective and the patient died of cerebral hemorrage 18 months later. Chromosome studies were made at the terminal stage. Preparations from peripheral blood cultured with PHA showed a normal male karyotype, but figures of chromatid breakage, gaps and exchanges were observed frequently. On the other hand, about 80% of the bone marrow cells had the karyotype of 50, XY, C+, F+, G+2. The post-mortem examination ruled out a malignancy. Preleukemic phase and chromosomal aberrations was discussed.

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The present paper is concerned with a case of von Willebrand's disease with particular reference to effect of blood transfusion on hemostatic defects.
The patient was a 10-year-old girl who had repeated nasal bleeding from early childhood, but had no hemarthrosis and gastrointestinal bleeding. Her parents were of consanguinous marriage, and her siblings had no history of bleeding tendency. Her maternal grandfather had frequent epistaxis and died of bleeding after surgical operation.
In physical examination she had no abnormalities. Examination of the peripheral blood showed a slight anemia without any significant change in count and function of leukocytes as well as blood platelets. Coagulation tests disclosed prolonged bleeding time, PTT as well as impairment of thromboplastin generating activity. Clotting time resulted in normal range. AHG level was highly reduced.
As to the treatment of this case, the transfusion of 200 ml fresh blood inproved the prolonged bleeding time and impairment of thromboplastin generating activity, and the effects continued for about 48 hours after transfusion.

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A case of primary acquired sideroblastic anemia was described, whose erythroblasts showed markedly reduced δ-aminolevulinic acid synthetase activity.
The patient, 68 year old Japanese female, was admitted with a history of anemia and congestive heart failure of 3 years duration.
By hematological study, marked hypochromic anemia without an apparent morphological aberration of erythrocytes was noted.
Examina tion of bone marrow disclosed intensive erythroid hyperplasia with minor megaloblastoid changes and maturation arrest.
Iron stores in bone marrow were greatly increased predominatly with ringed sideroblats. Serum iron was elevated and ferrokinetic study indicated the normal rate of iron clearance and depressed red cell iron utilization. In the studies on heme synthesis, incorporation of C¹⁴-glycine into heme, and activity of δ-aminolevulinic acid synthet-ase were found to be greatly reduced.
The pathogenetic significance of deficient ALA synthetase activity in sideroblastic anemia in this case was discussed.

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