The incidence of occurrence and the pathogenesis of renal lesions in diabetes mellitus were studied by means of proteinuria, renal function tests and kidney biopsies, and how the treatment of diabetes would affect the development of renal lesions was investigated. Also some observations on the clinical and histopathological findings about the group of Kimmelstiel-Wilson's syndrome were made. 1) About 30% of diabetics had glomerular dysfunction. This percentage increased for the young and elderly diabetics whose duration of diabetes were more than 5 years. Glomerular dysfunction did not seem to be related to the severity of diabetes but had some relation to the abnormal fat metabolism. Some diabetics with glomerular dysfunction showed increase of 17-ketosteroid in urine als the function of adrenal cortex. 2) Tubular dysfunction was observed more in longstanding elderly diabetics with glomerular dysfunction and seemed to be closely related to the severity of diabetes, especially such tendency was marked for young patients without glomerular dysfunction. 3) The Histological changes of glomeruli among the diabetics were mostly proliferation of mesangium that seemed to be features in early stage of renal lesions because such changes were observed since young generation and increased with duration of diabetes. The author assumes that glomerular nodule were caused by proloferation of Mesangium. Most of diabetics revealed tubular epithelial degeneration and sclerotic change of kidney blood vessels. 4) Specific lesions associated with diabetes were nodular formation of glomeruli (Kimmelstiel-Wilson's syndrome) that were observed in elderly group, especially among longstanding diabetics. The group with this nodular lesions were characterized by proteinuria which was most popular, hypertension, diabetic retinopathy and edema, but one has to be cautious of diagnosing them only from such clinical findings. The author suggested to call renal lesions with such clinical findings clinically; “diabetic nephropathy”. Any specific result of renal function tests in diabetics with this nodular lesions was not observed. 5) Renal functions were kept in superior condition for the diabetics whose metabolism were well-controlled from the early stage of diabetes than those who did not have the treatment and the difference between two groups became bigger as the duration were prolonged. Therefore in order to prevent the development of renal lesions, it is very important to control the carbohydrate metabolism since early stage, besides to keep the fat and protein metabolism normal.
In 60 cases of pulmonary tuberculosis treated with artificial pneumoperitoneum or with combination of pneumoperitoneum and chemotherapy, the relation between plasma protein fractions and clinical pictures was investigated, and following results were obtained. 1) In the plasma proteins of patients with pulmonary tuberculosis, there were decreases in albumin and increases in α-globulin, fibrinogen, γ-globulin fractions compared with normal ranges, but in a few cases the proteins were normal. 2) The patients that had normal plasma proteins or the change of one fraction except albumin were minimal tuberculosis, and all of 20 cases were effectively treated with pneumoperitoneum alone or combination of pneumoperitoneum and chemotherapy. 3) The patients that had the changes in α-globulin, fibrinogen added to albumin fractions were moderately advanced tuberculosis and 9 cases with slight degree of changes of plasma proteins were all effectively treated with pneumoperitoneum alone and 3 of 7 cases with moderate or intence degree of changes were uneffectively treated with combinated therapy. 4) The patients that had the changes in α-globulin, fibrinogen added to albumin and γ-globulin fractions were far advanced tuberculosis. In this group only 3 cases of slight degree of changes were effectively treated with pneumoperitoneum alone, but 9 of 21 cases with intence degree of changes were treated uneffectively with combinated therapy, namely in such cases good clinical effect could not expected even with the combination of pneumoperitoneum and chemotherapy.
The myocardial metabolism in dogs during starvation and during hypoproteinemia produced by plasmapheresis have been investigated, using the coronary sinus catheterization. In addition, the effects of glucose, mixed amino acid preparation, and cardiac glycosides on them have been observed. Following results were obtained. 1) After about a week of fast, the myocardial extraction of carbohydrates was markedly decreased (in some cases, the coronary arteriovenous differences of glucose, lactate, and pyruvate were negative) and that of fats was increased, accompanied by depression of the myocardial respiratory quotient. The myocardial extractions of oxygen and amino acids were scarcely altered. Cardiac function was generally depressed. During starvation, fat comes to main fuel in the heart instead of carbohydrate as in the other organs. 2) When dogs in the above condition were given 50 per cent glucose, the myocardial extraction of carbohydrates was markedly increased with the abnormally marked elevation of the arterial levels, that of fats and amino acids decreased, that of oxygen increased, and the myocardial respiratory quotient elevated. Following the administration of mixed amino acid peparation, the myocardial metabolism showed a tendency to return to the normal state, but the effect of it was inferior to that of glucose. Following the administration of digitoxin, there was no obvious change in cardiac metabolism and function. Following the administration of strophanthin, the myocardial metabolism was altered little, but the cardiac function was somewhat recovered. 3) In dogs with hypoproteinemia, changes in cardiac metabolism and function showed the same tendencies as in starved dogs, except for decrease of oxygen extraction. During hypoproteinemia, the heart derives its energy from fat mainly as during starvation. 4) When dogs in the above condition were given 50 per cent glucose, the myocardial metabolism showed a tendency to return to the normal state. After mixed amino acid preparation, the myocardial extractions of oxygen and carbohydrates were considerably increased, that of fats decreased, the myocardial respiratory quotient elevated, and thus the myocardial metabolism recovered remarkably. Concerning cardiac glycosides, the same results were obtained as in starved dogs.
The interaction between tissue slices and surviving medium (serum) in some aspects such as electrophoretic pattern of serum protein and titer of hemagglutinin was investigated. Liver and spleen slices from normal and immunized rabbit were survived in Warburg-type flasks at 38.5°C, under an atmosphere of 95% O2, 5% CO2, for 6 hours. Following results were obtained. The release of the antibody of the immunized tissue slices survived in normal serum was observed. 1) The rate of release of protein and non-protein nitrogen from normal and immunized liver and spleen slices were not different from each other. However, release of antibody from immunized tissue slices was markedly increased. 2) The release of beta-and gamma-globulin from liver slices was demonstrated and the rate of release of gamma-globulin was accerelated by immunization. The same results, however, was not obtained in spleen slices. 3) The release of serum protein (beta- and gamma-globulin) and antibody from tissue slices were modified by immunization. And the difference between liver and spleen was observed. From these results, it was revealed that the protein metabolism of tissue in vitro was influenced by immunization and liver and spleen slices showed different reaction in vitro by immunization.
In order to elicit the information concerning the mechanism of tuberculin-allergy and the antibody formation centers, the possibility of passive transfer of tuberculin hypersensitivity was tested under the following conditions: 1) When living cells isolated from such organs and tissues as the lung, spleen, lymph nodes, bone-marrow, liver and milky spots were transplanted from rabbits sensitized to tuberculin to non-sensitized rabbits. 2) When the above mentioned cells were destroyed and lysed by freezing and thawing or exposing to super-sound waves and transplanted from sensitized rabbits to nonsensitized ones. 3) When the living cells were transplanted from sensitized rabbits to non-sensitized guinea pigs. Results: 1) Even in rabbits, as in Chase's report on guinea pigs, passive transfer of the tuberculin type of hypersensitivity was possible by means of transplantation of the living cells isolated from the spleen and lymph nodes. Moreover 2) the living cells of lung sensitized also had the ability to transfer successfully and surely this type of hypersensitivity. But 3) When all these cells transplanted were destroyed, they lost this ability. 4) The cells of bone-marrow, liver and of milky spots, even in the living state, and the plasma in the sensitized rabbits had probably no such ability. 5) Passive transfer of the tuberculin type of hypersensitivity between heterogenic animals appeared unsuccessful, even though the living cells of the spleen and lymph nodes which were assured to have the ability of transferring successfully the hypersensitivity between homogenous animals, were transplanted.
For the purpose of elucidating the relationship between electrocardiographic changes and clinical and laboratory findings in liver diseases, 83 cases of acute and chronic hepatitis and cirrhosis (25, 20 and 38 cases respectively) including 13 cases which lapsed into hepatic coma were examined and the following results were obtained. 1) Pathological electrocardiographic findings were detected in 73.2 per cent of the whole patients, and the changes in hepatic coma were remarkable without exception. As the most common abnormalities, lowering of T-wave, ST-depression, low voltage and QT-prolongation were observed in 49.6, 29.3, 25.2 and 21.1 per cent respectively, and all these findings were more marked in the clinically severe cases. 2) No appreciable correlation was found between the electrocardiographic changes and the clinical findings such as disorders of nutrition, low blood pressure, cardiovascular murmurs, enlargement of the liver, splenomegaly, anemia and proteinuria. 3) Some parallelisms were noticed between the electrocardiographic changes and the abnormal results of liver function tests such as decrease in cholesterol ester quotient, shift to the right of the serum cobalt reaction, decrease in A/G ratio and increase in gamma globulin. Moreover, lowering of T-wave, ST-depression and low voltage were found more frequently in the group presenting abnormal serum protein patterns. Some discussions were made on the above results in reference to the concept of “hepatogene dysproteinãmische Myokardose (Wuhrmann)”.
We investigated the mechanism of the liver damage due to CC14 poisoning, especially concerning the mitochondrial functions, i. e. the capacity of oxidative phosphorylation and the respiratory enzyme activities, in relation to the optical properties, constituents and structure of mitochondria. 1. The reduction of P: O ratio occurred in acute poisoning in a day after injection of CC14, and recovered to normal level after 1 week. But this change was limited to the D.P.N. -linked reactions by use of α-ketoglutarate or pyruvate as a substrate, and when succinate was used as a substrate, we could not find any reduction of P: O ratio. V.E. protected completely the lowering of P: O ratio. 2. Succinate-Cyt. C. reductase and Cyt. oxidase activities tended to decrease slightly in the damaged liver, but DPN-Cyt. C. reductase activity clearly increased, suggesting the possible changes of mitochondrial structure. 3. Swelling of damaged liver mitochondria caused by orthophosphate, estimated by the reduction of optical density of mitochondrial suspensions, is less remarkable than that of the normal, and in other conditions we could find some differences between normal and damaged liver mitochondria. Light scattering method revealed difference of the degree of asymmetry at 45° between the suspensions of the normal and damaged liver mitochondria. 4. Lipid: total N, cholesterol and fatty acetals: fatty acid ester groups in the lipids of mitochondrial fraction increased in the CC14 poisoning, and acetals per mito chondria eq. to one gram liver increased markedly in the chronic poisoning. Both iodine value of lipids and peroxide formation of mitochondria, estimated by T.B.A. reaction, decreased. P32O4 incorporation into the lipids of mitochondrial fraction is markedly diminished. 5. From the results above reported we concluded that CC14 damaged liver mitochondria primarily, changed their structure, thus leading to the lowering of the capacity of energy utilization. The changes in the lipid constituents of mitochondria seemed to have any relationship to these dysfunctions.