Haruto Uchino

Preleukemic States in Atomic Bomb Survivors in Japan

Cytologic and cytogenetic studies were performed on the bone marrow cells in atomic bomb-exposed patients who had prolonged periods of blood disorders with termination of acute leukemia (group I, 6 cases) and without the termination (group II, 6 cases), and survivors who were in apparent good health (group III, 85 cases). All but one patient in group I, who were examined at the preleukemic state, had abnormal clones. In 4 out of 6 of group I patients, morphologic abnormalities of bone marrow cells taken 3-10 years before leukemic development were found, such as giant neutrophils or basophils, binucleated granulocytes or megakaryocytes, and bridge formation of chromatid in metaphases. All patients in group II had stable types of chromosome aberrations. The types of cytologic abnormalities were similar to those in group I, but the frequencies were a little less than those in group I. In group III, 14 persons were found to have stable types of chromosome aberrations, of which 11 persons had apparent but transient clone formations. Cytologic and clinical abnormalities were not observed in the group. The persistent and high percentages of cytologic and cytogenetic abnormalities in patients with prolonged periods of blood disorders, regardless of history of radiation exposure, would suggest a preleukemic state, and also give some clue to the problems of leukemogenesis.

Metabolic and kinetic study of thrombogenesis: regulatory mechanism in early step of platelet plug formation.

Abstract Metabolic and kinetic study of platelets to predict thrombogenic episodes were conducted on the subjects who had remarkable thrombocytosis and who had been subjected artificial heart valve replacement and put under antiplatelet therapy. Initial step of platelet plug formation are closely energy dependent. Epinephrine-induced aggregation of platelets in CML with thrombocythemia are impaired as well as metabolic response via citric acid cycle. This refractory response are also observed in the platelet under the antiplatelet therapy: dipyridamole, aspirin. Partial correction of those abnormalities by addition of PGE2 (F2α) suggested their participation in regulatory mechanism of aggregability and/or release mechanism. To evaluate clinical effects of these metabolic suppressive agents in vivo, kinetic study was done on those patients. Thrombocytosis above one million itself did not promote platelets consumption, however, implantation of artificial surface brought about mild increase of consumption resulting in mild thrombocytopenia. This kinetic study is proved to be promising to predict thrombogenic episodes and their prognosis.

Gastric intrinsic factor

Body iron loss f rom the intestine is caused by gastrointest inal bleeding in various diseases It is considered that a lot of cases of iron deficiency anemia are occured f rom GI bleeding. However it is difficult to measure the quantity of GI bleeding. By this reason, the examination of quantitative method for measurement of gasrointest inal bleeding was performed in several ways. The fecal excretion of radioactive chromium by GI bleeding after the administrat ion of 51Cr labelled red cell into the circulation, was considered to the most accurate method for quantitation of GI bleeding. There was no absorption of 51Cr in the GI tract following oral dose of 51Cr red cell and was no excretion of 51Cr to the GI tract from the circulation following intravenous injection of 51Cr labelled hemolysate. Whole body radioactivity af ter the administrat ion of 51Cr labelled red cell was measured daily using whole body counter. The activity decreased gradually and the all decreased 51Cr activity was recovered in urine in the normal case. Then the difference between the diminution of whole body activity and the urine activity meant the 51Cr loss by GI bleeding. The calculation of the volume of GI bleeding from the fecal 59Fe activity after the incorporation of 59Fe in circulating red cell was 20% lower than that of the results from 5~Cr method. A lot of quantity of 59Fe Hb was reabsorbed from intestine af ter the oral dose. It was considered that fecal 59Fe activity expressed the quantity of iron loss by GI bleeding instead of total bleeding volume. 59Fe activity in circulating red cell did not decrease during initial 90~100 days except the mixing to storage iron by hemolysis. In the cases having constant GI bleeding, the activity was decreased almost exponential fashion. From the rate of i ts decrease, average volume of iron loss could be calculated roughly. Whole body 59Fe activity was measured daily af ter the injection of 59Fe. The whole body activity decreased to 90% rapidly after the injection, when it recovered to the initial level when the all 59Fe incorporated into the circulating red cell. If bleeding was present, whole body activity decreased again gradually. From this grade of decrease, the amount of iron loss could be calculated. In one case of GI bleeding, fecal 59Fe activity corresponded well to the diminution of whole body radioactivity. However, in the other case, the quantity of bleeding was somewhat overestimated. The geometrical problems must he studied further . The fashions of GI bleeding in several clinical cases were demonstrated by fecal 5~Cr method. One ml. of GI bleeding daily on average was observed in 10 cases of normal subjects. The large variation of daily bleeding were found in the cases of gastr ic ulcer, oesophagial varices and gastr ie cancer. Two cases of iron deficiency anemia showed a large quantity of GI bleeding without any abnormal findings in GI tracts. It was imagined that some cases of iron deficiency anemia happened by this way. 0.5ml. of blood was mixed to one day feces and benzidine and guaiac reaction were tested on the sample. The both reaction were positive already. However, there was not clear correlation between these reaction and the bleeding volun~_e which was determined by 5~Cr method in actual fecal sample. It was concluded that 51Cr fecal method was the best method for the determination of bleeding volume.