The activity of the plasma thromboplastin were studied, representing the thromboplastin dilution curves with normal subjects as well as various diseases and measuring the plasma recalcified clotting time with diseases of the blood and the liver. Then the thromboplastin generation test (Biggs and Douglas, 1953) was discussed. Consequently a new method for thromboplastin generation was devised. Applying this method, the thromboplastin formation factors in plasma and serum were analysed, and the thromboplastin formation activity in normal subjects as well as in hemorrhagic diathesis, especially in hemophilia, was examined. The following conclusions were arrived: (1) The thromboplastin dilution curve shows the degree of the plasma thromboplastin activation. With the prolongation of recalcified plasma clotting time, the degree of the activation decreases in hemophilia, aplastic anemia, idiopathic thrombocytopenic purpura (ITP) and disease of the liver. (2) The thromboplastin dilution curve which is obtained by using tissue thromboplastin produced from brain, testicle and muscle of hemophilia forms a peculiar one. (3) There is enough ground for further examination and study with thromboplastin generation test which was introduced by Biggs and Douglas in measuring plasma thromboplastin factors. Therefore it cannot be considered as being a competent method. (4) The new method for thromboplastin generation was devised and hereby described. (5) For the plasma thromboplastin formation, platelets not less than 100 X 104/cmm are needed, but even though the number of platelets increase more than the above, it does not affect the degree of the plasma thromboplastin formation. (6) When plasma is diluted 1 in 5 with normal saline, the activity of the plasma thromboplastin formation is the strongest. (7) It is observed that there are the factors for thromboplastin formation in plasma, which are absorbed by barium sulfate, barium carbonate and aluminium hydroxide and eluted from the barium sulfate absorbant by sodium citrate. (8) Antihemophilic globulin (AHG) is present in the 33 per cent saturated ammonium sulfate fraction of normal plasma and plasma thromboplastin component (PTC) is present in the 34 to 50 per cent saturated fraction. They exert their actions only when exist together. (9) A thromboplastin formation factor, which exerts its action in concert with AHG, is present in the 34 to 50 per cent saturated ammonium sulfate fraction of normal serum and its activity is stronger than PTC in the 34 to 50 per cent saturated ammonium sulfate fraction of normal plasma. (10) A new factor was found in the 51 to 70 per cent saturated ammonium sulfate fraction of normal serum. This factor does not exert its activity independently but contributes to the thromboplastin formation when AHG, PTC and platelets exist. It was named “Thromboplastin Generation Serum Factor (TGSF)”. (11) TGSF exists in an inactivated form in plasma and is strongly activated in serum. Its activity is destroyed by heating at 56°C for 10 minutes and absorbed by barium sulfate. (12) The thromboplastin generation test was performed with normal subjects and the normal range of variation in the thromboplastin generation was decided. (13) The thromboplastin formation activity of 10 cases of hemorrhagic diathesis except hemophilia is within the normal range. (14) 3 cases of patients which had been diagnosed as hemophilia by the ordinary laboratory methods, were reexamined and hemophilia and PTC deficiency were classified.
The author has made a study of the influence produced in the intestinal absorption rate of pulmonary tuberculous patients and rabbits by pumping gases intraperitoneally using such gases as oxygen, carbon dioxide and nitrogen. The results observed are as follows: (1) The intestinal absorption rate was definitely increased by short term normopressure pneumoperitoneum using oxygen with each subsequent intraperitoneal pumping. After reaching a maximun value at the 6 at 7th pumping, the intestinal absorption rate decreased gradually. The rate decreased more and more after transient high-pressure pneumoperitoneum, but it showed higher values than those before the first pneumoperitoneum. (2) The rate showed a tendency to decrease with each subsequent pumping in cases of short term normopressure pneumoperitoneum using carbon dioxide. (3) Tne fluctuation of the rate using nitrogen was almost the same as that using carbon dioxide. However, tendency later showed more rapid decrease. (4) The intestinal absorption rate in all the groups of gases was less than that of prepumping mean value when the normo-and highpressure pneumoperitoneum was established for a long time. This was especially remarkable in the nitrogen group.
It is known that glucuronic acid, beside strongly accentuating the function of the liver, has the effect of detoxifying various toxic substances in living organisms by agglomerating and forming so-called agglomerate glucuronic acid. By measuring the time required for coagulation of serum to which glucuronic acid (Glonsan) is added and heat is applied, a marked difference in the length of time was observed between liver diseases, normal subjects and patients of various diseases. The author then utilized this difference for testing the function of the liver and obtained the following results in clinical practice. Experimental Method: 0.5cc of the tested serum was taken in a small test-tube, 0.5cc of glucuronic acid solution containing 50mg of glucuronic acid was added to it and mixed by shaking, placed in a bath preheated to 60°C and the time required for the coagulation of the serum (disappearance of all fluidity) was measured, to estimate the existence or the degree of liver detsturbance. When the time was shorter than 25min. the result was marked negative (-), when between 25 and 30min. quasi-positive (±), when 30-35min. weakly positive (+), when 35-40min. moderately positive (++), when 40-45min. strongly positive (+++) and when more than 50min. extremely positive (++++). Results: All the 20 normal subjects showed negative results, while the 8 acute hepatitis cases, the 6 hepatic cirrhosis cases, the 17 hepatic carcinoma cases and the 2 cases of other liver diseases showed positive G-reaction in every case (100%). The Gros's tests conducted simultaneously showed the rates of positive reaction of 50%, 80%, 87.5% and 100% respectively, while those of Takada's tests were 60%, 100%, 76.4% and 100% per group. In almost all cases of non-hepatic diseases, the results of G-reaction tests were negative, and animal experiments showed that the grade of positiveness rose in parallel with the rise in the degree of the functional disturbance of the liver.
1. Albino rats were fed a choline-deficient diet for 8 months. Some of the rats were then killed and the remaining animals were fed the therapeutic diet containing 30% of casein and 40% mg of choline chloride for 6 months. Microscopic examination and quantitaive determinations of liver fat, liver collagen and serum protein were carried out on these animals. 2. The livers of the rats fed the choline-deficient diet were finely granular, and microscopic examination showed fatty metamorphosis, ceroid accumulation, and fibrosis of the liver which began in the non-portal area. Receiving the dietary treatment fat disappeared rapidly, but there was no recognizable effect on fibrosis and ceroid accumulation. 3. Liver fat increased remarkably on the choline-deficient diet, and returned to nearly normal level on the therapeutic diet. In the rats fed the choline-deficient diet for more than 18 weeks liver fat decreased as fibrosis or ceroid accumulation progressed. 4. Liver collagen increased on the Choline-deficient diet, but did not seem to decrease after the treatment. 5. On the choline-deficient diet serum albumin and albumin globulin ratio decreased markedly, but the increase of γ-globulin is not significant statistically. Reciving the dietary treatment albumin returned to narmal and γ-globulin increased significantly. Albumin globulin ratio increased significantly, but did not return to normal level.
By careful examinations on 219 cases of out-or in-patients with anemia in the clinic, the author obtained the classification of anemias shown in Table 1.19 of the cases were of no clear cause, and they belonged to the anemia type which was classified as macrocytic non-megaloblastic anemia. Prof. Matunaga named this anemia type X-anemia. Systematic blood examinations of this X-anemia and experimental studies on deficiency of vitamin B2-group with rats were made for the genetic analysis from the resulting blood pictures. The pictures of the obtained peripheral blood and bone marrow and clinical data are shown in Tables 2, 3, 4, and 5. Table 6 shows the diet formula of vitamin B2-group deficiency for the animal experiments. The experimental data are shown in Table 7. The results obtained in the clinical and experimental studies are as follows: 1. X-anemia is mostly encountered in women but has no direct relation to pregnancy. 2. Signs and symptoms are mainly due to gastrointestinal disorder. As contrasted with pernicious anemia, however, gastric juice is not achylic as a rule. 3. The blood picture shows a macrocytic and hyperchromic anemia, and in the bone marrow no megaloblast appears but macroblast increases markedly in number. 4 Judging from the experimental results with rats, B2-group deficiency does not seem to be the cause of the anemia. 5. Using iron, cupric perparates, folic acid, vitamin B12 or liver preparates or by transplantation of the anterior lobe of pituitary gland, the author has proved no effect in reducing the anemia. Blood transfusion is the only treatment effective. 6. Although the prognosis of this anemic condition has no direct relation to life span, the clinical condition deteriorates progressively though slowly. 7. It has not been determined conclusively whether this anemia type is morbus sui generis or a syndrome due to other diseases. Mal-nutrition in a broad sense may, however, be one of the causes of the anemia. The author's presumption is that this X-anemia is due to the insufficient absorption of an unknown anti-anemic factor from the digestive tract because of its functional disorder. If the presumption be true the anti-anemic factor should be entirely different from the extrinsic factor in pernicious anemia. 8. The author terms this X-anemia type “benign, normoaciditic, macrocytic. hyperchromic, and non-megaloblastic anemia.”