Using dogs, cats, and monkeys for test animals and with a concentric cylindrical electrode devised so as to obtain the electric field of any desired area, the author estimated the stimulation threshold as well as calculated the number of Betz cells contained in the electric field by stimulating the cerebral cortex motor area of these animals; 1) Any symptom of motor response could not be observed when dogs, cats and monkeys were stimulated with the concentric cylindrical electrode less than 1mm in diameter. When it was more than 1mm in diameter, some response could be found, but could not get any response sometimes at some spots even if it was more than 1mm in diameter. This caused when the spots had thin density of Betz cells. 2) The stimulation threshold of the forefoot center and the hindleg center in the cortex motor area of dogs is about equal or a little lower in the forefoot center, whereas in the case of cats and monkeys the stimulation threshold of the forefoot center is clearly lower than that of the hindleg center. 3) In order to elicit the motor response it is necessary to stimulate 16-19 Betz cells of the forefoot center and 22-26 Betz cells of the hindleg center in the dog; 18-23 cells of forefoot center and 29-34 cells of the hindleg center in the cat; and 16 cells of the forefoot center and 25 cells of the hindleg center in the monkey. 4) The difference of the stimulation threshold in the same center depends upon the difference in the density of Betz cells in the center. 5) The difference of the stimulation threshold in different centers depends upon the difference in the number of Betz cells required to elicit the motor response.
The clinical investigation regarding to vitamin B1 metabolism was performed on rheumatoid arthritis during one month of admission, during which period the various antirheumatic agents were given to these patients. 1) The total thiamine levels of blood in rheumatoid arthritis was low compared with normal healthy people, specifically low in ester type suggesting the decrease of phosphorylation. There was also present the advancements of erythrocyte sedimentation rate and disturbed function of liver with advance of “stage” and “class” of this disease. The decrease of rate of phosphorylation was seemed to be parallel to them. 2) It is able to consider that the vitamin B1 deficient of rheumatoid arthritis is due to the decrease of vitamin B1 level in blood resulted from the lower efficiency of vitamin utilization. 3) It is concluded from the observations of clinical symptoms at the rheumatoid arthritis that as the temporary elevation of vitamin B1 level in blood by administration of large dosage of vitamin B1 appears to be insufficient in analgetic activity for rheumatoid arthritis, so it seems better in the treatment by corticoids with small dosage of vitamin B1 administration for long period rather than by large dosage for short period. 4) For the improvement of vitamin B1 metabolism, thiamine propyl disulfide and cocarboxylase are more effective than the other, and the combind administration of vitamin B1 with ATP was effective, specifically for the elevation of ester type of vitamin B1. It will be concluded that the protecting treatment of liver function is also useful not only for elevation of the value of vitamin B1 in blood but also for the improvement of general symptoms of rheumatoid arthritis.
With the purpose to take the statistics of clinical records of leukemia, the author analyzed the total of 242 cases of leukemia admitted in the leading hospitals of the Chugoku-Shikoku District (excluding Hiroshima Prefecture) and obtained the following results. 1. The total cases of leukemia can be divided into 88 cases of acute myelogenous leukemia, 70 cases of chronic myelogenous leukemia, 48 cases of acute lymphocytic leukemia, 4 cases of chronic lymphocytic leukemia, 2 cases of erythro-leukemia, 17 cases of monocytic leukemia, 8 cases of unclassified acute leukemia, and one completely unclassified case. 2. As for the difference in the incidence by sex, the male occupies 62 per cent of the whole, but 75 per cent of lymphocytic leukemia proving to occupy a far greater proportion of male whereas in monocytic leukemia the female occupies a far greater proportion as much as 53 per cent. 3. As for the age distribution those under 25 years of age occupy the majority. According to the types, in the acute leukemia, especially in lymphocytic leukemia the greater part is occupied by younger persons, while in chronic leukemia those in the age range between 35-and 39 years present the peak, and even in the age beyond this range can be found quite many cases. The same also applies to monocytic leukemia. 4. No characteristic feature attributable to occupation can be recognized. 5. There have been 3 cases (1.3%) showing family history of leukemia and 17 cases (7.0%) showing family history of cancer. 6. There are included 5 cases of atomic bomb survivors. As for the anamnestic history there are 6 cases of malaria and 5 cases each of pleurisy and pneumonia. 7. When the symptoms at the Onset of the disease such as subjective complaints and somatic symptoms are arranged in the order of the frequency by the types, they are as follows. Initial symptoms: in acute myelogenous leukemia: fever, general malaise, anemia, hemorrhagic tendency; in acute lymphocytic leukemia: fever, general malaise, anemia, the swelling of the lymph nodes, and pain; in chronic myelogenous leukemia: general malaise, the swelling of spleen, anemia, bulging of the abdomen, fever; in monocytic leukemia: fever, general malaise and hemorrhagic tendency. Subjective complaints: In acute myelogenous leukemia: fever, bleeding tendency, anemia, general malaise; in acute lymphocytic leukemia: fever, anemia, swelling of the lymph nodes, general malaise, hemorrhagic tendency; in chronic myelogenous leukemia: tumor in the abdomen, (bulging of the abdomen and swelling of the spleen), general malaise, fever, anemia, pain; in monocytic leukemia: fever, general malaise, bleeding tendency, anemia, and pain. Somatic symptoms: in acute myelogenous leukemia: anemia, fever, general malaise, fatigue, general emaciation; in acute lymphocytic leukemia: anemia, fever, general malaise, fatigue, emaciation; in chronic myelogenous leukemia: anemia, general malaise, fatigue, fever, emaciation: in monocytic leukemia: anemia, fever, general malaise, fatigue and general emaciation. 8. Dilatation of lymph nodes and swelling of the spleen can be found in 77.3 per cent and 49.0 per cent respectively of acute myelogenous leukemia: in 93.8 and 66.7 per cent of acute lymphocytic leukemia; in 61.5 and 94.3 per cent of chronic myelogenous leukemia; in 100.00 and 100.0 per cent in chronic lymphocytic leukemia; and in 76.4 and 23.5 per cent of monocytic leukemia, especially the enlargement of the spleen in chronic myelogenous leukemia is marked. 9. Hemorrhagic tendency can be observed in 70 per cent of acute myelogenous leukemia and acute lymphocytic leukemia, and in 40-60 per cent of other types. 10. Symptoms of the digestive organs are stronger in acute leukemia than in chronic leukemia. In the latter the feeling of bulging abdomen is frequent, while in acute myelogenous leukemia and monocytic leukemia stomatitis and buccal ulcers are more frequently encountered.
The author analyzed clinically and statistically 67 cases definitely diagnosed as leukemia by bone-marrow tissue culture in our clinic during the period from January 1954 to October 1957. The results are described in the following. 1. These 67 cases can be divided into 16 cases of acute neutrophilocytic leukemia, 8 chronic neutrophilocytic leukemia, 2 acute basophilocytic leukemia, 12 acute lymphocytic leukemia, one chronic lymphocytic leukemia, 25 monocytic leukemia, and three others, showing an extremely large number of monocytic leukemia as compared with other Japanese statistics, occupying over one third of the whole. For this reason it seems that monocytic leukemia has previously been included in chronic myelogenous leukemia. Furthermore, it is indeed significant that the two cases of acute basophilocytic leukemia have been confirmed by bone-marrow tissue culture. 2. With the exception of the paucity in the number of infant cases, as our clinic is of internal medicine, there are no particular differences with respect to the sexual classification, age distribution and occupational classification. 3. One case (1.5%) having family history of leukemia, 15 cases (22.7%) having family history of cancer, and 2 cases (3.0%) of atomic bomb survivors have been encountered. 4. As for the characteristics of clinical symptoms all the symptoms of acute myelogenous leukemia proceed acutely, accompanied with marked fever and hemorrhagic tendency along with a high incidence of disorders of the digestive, respiratory and circulatory functions. This type also shows albuminuria in 43.8 per cent and glucosuria in 15.4 per cent in urine. On the other hand, the swelling of the spleen, generally accepted as the symptom specific to myelogenous leukemia, can be encountered only in 25 per cent. Acute lymphocytic leukemia on the whole proceeds more slowly than acute myelogenous leukemia. Speaking only of the symptoms at the onset of the disease, it lacks the hemorrhagic tendency, but its characteristic trait is the complaint of the enlarged lymph nodes. It may be natural to expect the enlargement of lymph nodes in practically all cases of this type, but the swelling of the spleen can also be encountered in the majority, showing the enlargement of lymph nodes accompanied with the swelling of the spleen and the liver in well over 60 per cent. The incidence of pain in the bones, though not so high, is more often observed than in other types, and the acceleration of the urobilinogen excretion in urine is also a characteristic symptom. There is no question of doubt that all symptoms of chronic myelogenous leukemia are milder than those of the acute type, nevertheless, anemia can be found in 90 per cent and fever in 60 per cent. From the standpoint of the symptom at the onset, subjective complaint and the symptom actually present, what can be considered the main characteristic of this type, is the swelling of the spleen, observable in nearly all cases and the giant spleen swollen well over 4 finger breadth below the left costal arch can be encountered in over 60 per cent. On the contrary, the cases with the enlargement of lymph nodes is not so abundant. Monocytic leukemia more often commences with hemorrhagic tendency than any other type, amounting to 40 per cent. Although the incidence of this trend decreases in later stage and becomes about the same as in other type of leukemia, it is worthy of note that the incidence of buccal hemorrhage reach as much as 40 per cent at the same stage. What might be considered as most characteristic of this type is that the severity of almost every symptom is intermediate between the acute type and chronic type. In this type the enlarge ment of the lymph nodes is quite frequent, amounting as much as three quarters of all, while the swelling of the spleen can be found only in less than 30 per cent.
The author studied the trends of serum cholesterol, lipoprotein, and proteins, mainly in leukemia and various blood diseases, and obtained the following results. The subjects of the present investigation were the cases diagnosed as such by bonemarrow tissue cultures and hematological examinations. 1. The cholesterol value in leukemia is almost at the normal level, showing not any marked difference by the type of the disease, but the ratio of β- and α- lipoproteins generally presents an increasing tendency. As for the trend of serum proteins on the whole a decrease in total concentration and albumin and an increase in γ-globulin are the common changes, and the differences by the type can not be considered to be marked. Only in mono cytic leukemia the decrease in albumin and the increase in γ-globulin are marked. 2. Hypoplastic anemia shows the normal level of cholesterol, but it is interesting to note that the total cholesterol, ester cholesterol as well as the ratio of ester to total chole sterol are all in the decreasing order of type I>type III>type IV. Moreover, a decrease in α-globulin and an increase in γ-globulin in the serum protein content can be observed. As for the other anemias Banti's disease shows an increase in the lipoprotein ratio, a marked decrease in serum protein, and an increase in γ-globulin; idiopathic hypochromic anemia a decrease in serum proteins; a single case of hemolytic anemia an increase in cholesterol, a decrease in the serum protein content and albumin fraction and an increase in γ-globulin. In addition, in one case of hookworm anemia an extremely high value of the lipoprotein ratio, a decrease in albumin and an increase in γ-globulin can be recognized. 3. In cancer a decrease in cholesterol, serum protein content, and albumin fraction and an increase in γ-globulin can be recognized, but as for the differences in the site only hapatoma shows a marked change in serum protein and fractions. 4. Choresterol in idiopathic thrombocytopenic purpura is decreased, and in one of them a decrease in albumin of serum protein fractions and a slight increase in γ-and β- globulin can be observed. In lymphogranulomatosis a decrease in albumin and an increase in γ-globulin are marked, and in one case of reticulum cell sarcoma a decrease in cholesterol, the serum protein content, and albumin as well as an increase in γ-globulin can be recognized.
By adding such substances as polytamine, a derivative of amino acids (a by-product of caseous fermentation of cow's milk), by-product of cow's milk caseous hydrolysis with acid, and ten different non-essential amino acids contained in polytamine directly to rabbit bonemarrow tissue culture, the author estimated the tissue growth area and cell density and studied influences of these substances on the production of the leucocyte series in the bone marrow. The results are as follows. 1. Both polytamine and by-product of cow's milk caseous hydrolysis with acid can increase the growth area slightly more than the control only in a high concentration. 2. With addition of L-hydroxyproline in the concentration from 0.1 to 0.0001 per cent, this substance in any concentration within this range increases the growth area and cell density 2-3 times that of the control, showing the greatest values among amino acids used in the present experiment. 3. Both L-proline and L-arginine in high concentration increase the growth area twice the control, and slightly at low concentration. 4. L-Cysteine, L-tyrodine, and DL-serine each in a proximal concentration can only increase the growth area slightly more than the control. 5. L-Aspartic acid and L-glutamic acid, glycine, and L-ornithine show hardly any significant difference as compared with the control.
By adding polytamine, by-product of cow's milk hydrolysis and 10 different non-essential amino acids as already mentioned in Part 1 directly to rabbit bone-marrow tissue culture, the author studied influences of these amino acids on the wandering velocity of mature pseudoeosinophils in the bone marrow. 1. Polytamine and by-product of cow's milk caseous hydrolysis do not at all affect the wandering velocity of pseudoeosinophils. 2. Hydroxyproline, proline and cysteine, when added in a high concentration, all accelerate the wandering velocity but they do not at all affect the wandering velocity when added in a low concentration. Moreover, cysteine has been found to accelerate the wandering velocity even 12 hours after the start of culture just as much as at the third hour. The other two accelerate the wandering velocity markedly up to the sixth hour of culture. 3. Glutamic acid accelerates the wandering velocity slightly. 4. Arginine, serine, glycine, tyrodine, aspartic acid, and ornithine have neither accelerating action nor inhibitory action on the wandering velocity of pseudoeosinophils.
The author studied influences of hydroxyproline on erythropoiesis by means of rabbit bone-marrow tissue culture and also used this substance in the treatment of hypoplastic anemia; and obtained the following results. 1. In loading hydroxyproline directly to rabbit bone marrow tissue culture(fluid medium), no significant change can be recognized in the number of erythrocytes and reticulocytes. As for the change in hemoglobin (Hb) content with addition of this substance, Hb decreases in the control whereas it increases slightly when added in a high concentration. 2. In the tissue culture of the bone marrow (cover slip method) obtained from sternum of 5 cases of hypoplastic anemia loaded with hydroxyproline, the tissue growth has been accelerated in three cases. The two unaffected cases turned out to be of panmyelophthisis type. 3. Of 5 cases with hypoplastic anemia to three cases daily intravenous injection of 150-300 mg hydroxyproline was given. As the result all of them showed an increase the leucocyte count, but the erythrocyte count and Hb increased only in one case and it proved to be ineffective in other two cases.
For the purpose to learn the relation between the catalase activity of liver and the disease the author performed the estimation of catalase activity in the liver from the autopsy materials. Prior to perform the estimation on the autopsy materials the changes in the activity of the enzyme after the death have been checked on rats with a certain period of time after killing the animals. The tests proved that no change occurs in the activity in those preserved at 1 to 2 C in a ice chamber 24 hours after the death, though a marked decrease can be seen after 17 hours at 37 C. On the basis of this observation all the autopsy materials are taken within 8 hours after the death. As the results it has been found that the liver catalase decreases markedly in its activity in some disease as revealed by estimating with the slightly modified method of Bonichsen, Chance and Theorell. The liver tissues from 5 cases bearing malignant neoplasms and having tumors in the liver show a markedly low activity in catalase, 65.7% of the normal level in mean value, and the tumor tissues themselves in the liver are found to be extremely low in activity, 27.5%. A relatively low activity also can be seen in the liver from another tumor-bearing individuals, in which no metastasized tumor in the liver has been found, 82% of the normal level. With one exception of lymphosarcomatosis, where the activity have been found to be 1/10 of the normal level, in four cases of leukemia (2 monocytic leukemias and 2 lymphocytic lekemias) the activity has been found to be 64.8% of normal level. In four cases such as uremia, nephroses and so on, in which the metabolic activity is supposed to be lowered, relatively low levels have been found in the activity of liver catalase (82.5% in mean value). In 8 cases died of hemorrhage, benign tumor in brain and others the catalase activity of liver are kept almost at normal level. These observations show that the lowered catalase activity in liver does not necessarily be accompanied by the tumor formation.
In the first report the author described that the activity of liver catalase dropped markedly in the tumor-bearing individuals and moderately in some diseases like nephrosis uremia and othes. In this paper the author shows the experimental results carried on the liver of rats fed D.A.B. Feeding of D.A.B. for 6 weeks has raised the liver catalase activities extremely as high as about two times those of normal animals. Even in the liver developing tumors 4-5 months after D.A.B. feeding, the catase activities are found to be still as high as 2.4 times of normal level, though the tumor tissues themselves show an extremely lowered activity with some differences between the different types of tumors. Rather low levels of activity are found in the tumor developing as a mass with the expansive growth, 13 per cent of the normal level in mean value, comparing to those developing to the infiltrative pattern 130%. This will be due to the contamination of the normal liver cells in the latter, as the tumor tissues taken for the estimation can not be separated completely from the surrounding normal tissues. These results show that the catalase activity of liver is raised by affecting with D.A.B. showing the level as almost 2.5 times as high as that of normal rat liver. This level is kept in the stage of the development of tumors, but an extremely lowered level in tumor tissues. Any gradual changes of catalase activity from the D.A.B. affected tissues to the tumors can not be found showing occurrence of spontaneous change in the catalase activity by tumorization of cells.
I have conducted an experiment, at the end of being complete hunger, to prolong the living days of rabbits being administrated the mononutrient such as water, glucose, methionine, olive oil, alcohol, as well as vitamin B1; and then by using Tiselius electrophoretic apparat, examinined those changes that occur to serum protein fraction, the blood changes and etc., by administering mononutrient; by which arrived at the following results. In this chapter I have obtained the almost same result with the first chapter of being incomplete hunger, by administering the mononutrient, and especially, it is effective glucose as well as alcohol to prolong the living days of rabbits in case of administration the mononutrient at the end of being complete hunger.
In the study of changes in the production of blood cells and hemoglobin of the bone marrow in rabbits infected with various pyogenic bacteria, the author obtained' the following results: 1. In giving the intravenous daily injection of Streptococcus viridans (0.5mg/kg) to four groups of rabbits for consecutive days, one, four, seven and 14 times each respectively, taking daily blood counts of each group, and conducting bone-marrow tissue culture after respective injection, it has been found that peripheral leucocytes (especially pseudo-eosinophils) decrease in number immediately after the injection, but the number increases after 12 to 24 hours; and this process is repeated at each injection. Moreover, anemia, gradually progressing, becomes most pronounced around the seventh injection, and thereafter it turns to recover by degree. When the bone marrow tissue is cultured at the stage where leucocytes are on the increase; in the case of cover-slip method the relative growth rate increases, reaching the maximum after the seventh injection and tends to return to the normal level after the fourteenth injection, and the cell-density index remains at the normal level or is increased slightly, indicating an increase in the leucocyte series of the bone marrow. In the fluid medium cultures performed at the same time as mentioned above, the increasing rate of erythrocytes, reticulocytes, and hemoglobin of the bone marrow falls, and the degree of such a change more or less coincides with the changes in the anemic conditions of the peripheral blood. 2. When heat killed Streptococcus viridans (a daily dosage of 0.5mg/kg) is injected four consecutive days, such changes in blood and bone-marrow tissue cultures as mentioned above are slight; and when Streptococcus haemolyticus (0.5mg/kg), Staphylococcus aureus (0.5mg/kg) or Staphylococcus albus (1.0mg/kg) is injected four consecutive days, similar blood- and bone-marrow tissue culture findings can be obtained as in the case of four consecutive injections of living Streptococcus viridans, showing not any significant difference by strains of bacteria. Thus the author obtained the findings in bone marrow that amply endorse the changes in the peripheral blood under pyogenic infection by bone-marrow tissue culture.
In the present experiment the author pursued changes occurring in the functions of pseudo-eosinophils of the bone marrow of the rabbits infected with various pyogenic bacteria and obtained the following results: 1. In the periodical observations on the functions of pseudo-eosinophils of the bone marrow after intravenous injection of Streptococcus viridans (0.5 mg/kg) for consecutive days of one, four, seven, and fourteen respectively, the wandering velocity is slightly increased in the entire course. On the other hand, the carbone particle phagocytotic ability falls to the lowest level after the fourth and seventh injections and it tends to recover after the fourteenth injection; and in the neutral-red vital staining pseudo-eosinophils stain quickly and deeply, proving likewise the fall in function and the change takes place in parallel with the change of phagocytotic ability, and this fall in the functions from the standpoints of carbon-particle phagositosis and vital staining occurs when the systemic conditions and anemia in the test animals are aggravating and it also coincides with the stage where the production of leucocytes in the bone marrow is vigorously carried out. 2. When the results of four consecutive daily injections of the heat-killed Streptococcus viridans (0.5mg/kg) are compared with those of four similar injections of living bacteria, these changes as mentioned above are slight. Four consecutive injections of Streptococcus haemolyticus (0.5mg/kg), Staphylococcus aureus (0.5mg/kg), or Staphylococcus albus (1.0mg/kg) give the similar findings as in the case of four consecutive injections of living Streptococcus viridans; and there are no marked differences by strains of bacteria. From these it may be inferred that the dissociation in the functions of leucocytes is due to the overproduction of leucocytes, because the cells are being rapidly multiplied but immature from functional point of view.
In the bone-marrow tissue culture of the patients with subacute bacterial endocarditis the author obtained the following results: 1. In the case of cover-slip culture, the relative growth rate is normal both before and and after the treatment of patients, but the cell-density index is normal or in some cases with a decrease in bone-marrow nucleated cells it is diminished. 2. In the case of the tissue culture in a fluid medium, the increasing rate of erythrocytes, reticulocytes, and hemoglobin is markedly low before the treatment, but it recovers with treatment. 3. The wandering velocity of neutrophils in the bone marrow has been found to be normal or slightly accelerated. 4. The carbon-particle phagocytotic ability of neutrophils in the bone marrow is markedly decreased before the treatment, but it recovers to normal when the patient is treated. 5. As for the neutral-red vital staining of bone-marrow neutrophils, these cells stain quickly and deeply, indicating a decrease in the functions, but this condition is restored to normal by treatment. In the present paper the author stated that the examinations of the bone marrow by tissue culture with emphasis on the carbon-particle phagocytosis served a quite significant purpose for clinical course observations.
With bromine the author has experimented allergic dermatitis and the following results have been obtained. (1) It was recognized that bromine easily combined with serum protein to become the brominated serum protein. (2) The serological chemical properties of the brominated proteins were recognized by experiments showing the results of reaction between the brominated human serum antiserum of rabbits, and the brominated egg albumin. (3) Positive effects to induce hypersensitiveness were observed to the skin of the same rabbit immunized by the brominated human serum with the injection 0.2cc of 1:64, 000 dilution of bromine solution. (4) Different antigenicity has been recognized between the brominated human serum and the human serum by “Oudin's serum agar technic”. (5) Discharge of the bromine in the urine of guinea-pigs intravenously injected as antigen 1 cc of 1:3 dilution of pure bromine solution or 1 cc of brominated human serum (pure bromine solution 1: human serum 1: phosphate buffer 1) was so slackness that the bromine was demonstrated 85 long days after the injection. (6) Guinea-pigs were used as experimental animals and the sensitization were proved by the methods of intravenous, intracutaneous and subcutaneous injections of bromine solution or brominated human sera, and positive effects of inducing hypersensitiveness of the skin were obtained. The brominated protein has not been recognized different from the bromine solution in their sensitization of guinea-pigs.
The author made experiments on the professional allergic dermatitis with benzoyl chloride. The results were as follows. (1) The serological chemical properties of benzoylated proteins were recognized in the rabbit serum by applying repeated an soy-bean oil solution of benzoyl chloride (10%) on the rabbit skin. Positive effects to induce hypersensitiveness of the skin with benzoyl chloride in the same rabbit were obtained. (2) The rabbit received intravenous injections of a solution containing 0.2% of benzoylated human sera were tested 3 weeks after the 7th injection. It was obserbed that the benzoylated human sera antirabbit serum had a chemical specificity of benzoyl chloride which reacted with benzoylated proteins. (3) Positive effects of hypersensitiveness on the skin with benzoyl chloride were obtained to the same rabbit sensitized by intravenous injections of benzoylated human sera. (4) Hypersensitiveness of the skin was confirmed on the guinea-pigs sensitized actively by intracutaneous injections with benzoyl chloride.
The sensitization of guinea-pigs with para-phenylendiamine. (1) Sensitization of guinea-pigs with para-phenylendiamine could be obserbed more stronger rather with 1, 000 or 10, 000 times dilution of para-phenylendiamine than 100 times dilution of it. (2) The completely oxidized para-phenylendiamine formed Bandrowski's base, and consequently the sensitization of guinea-pigs disappeared entirely. (3) Para-phenylendiamine showed the strongest hypersensitiveness with the skin of guinea-pigs of ortho, meta and para, three isomers of phenylendiamine. (4) Hypersensitiveness of the skin could not be comfirmed by the ordinary method to judge when allergens and reagents were heterogeneous isomers of phenylendiamine each other. (5) Positive effects of the skin hypersensitiveness were observed on the guinea-pigs sensitized with any one of three isomers of phenylendiamine fifteen minutes after intravenous injection of 8-10cc trypanblue per the guinea-pig's kilogram which should follow immediately the test injection of other kind isomer than the isomer used as the sensitization.
After intravenous injection of 3 mg/kg sinomenine into the dog, the reduction in the histamine contents in the skin (ear margin, perivulvar region, lip and back skin) and in joint capsules (shoulder, hip and knee joints) as well as the manner of its recovery later on were studied. In parallel with this study their morphological changes were observed by counting the number of mast cells in the skin (lip and back skin) and in joint capsules (shoulder and hip joints). For the duration of the period between five hours and five days after the sinomenine injection the contents of the skin histamine in the ear margin and back were reduced to about 40 per cent of the normal values while that in the lip and perivulvar regions down to about 20 per cent. The histamine contents in the joint capsules five hours afterwards down to about 10 per cent the normal level. The recovery of histamine contents in the skin thereafter was extremely slow, returning to 90 per cent of the normal level in the back skin and only 50-60 per cent in the skin of ear margin, genital area and lip 40 days after the injection. However, the recovery of the histamine values in joint capsules was much more rapid than that in the skin, returning to 80 per cent the normal already 10 days afterwards. The mast cell counts both in the skin and joint capsules reached the minimum during the period between five hours and five days after the injection: in the back skin it was about 40 per cent the normal; in the lip skin about 20 per cent; and in the capsules of shoulder and hip joints down to 20 per cent, and thereafter the recovery in the skin was slower than that in joint capsules. The proportion of disrupted mast cells was greatest in the specimen prepared five hours after the injection, and in the skin and joint capsules about 90 per cent of the total was disrupted; but by the fifth day almost no disrupted cells could be observed. As for the morphology of the disruption, the swelling, degranulation, the extrusion or scattering of granules outside the cell could be observed, and these granules show metachromasia as their characteristic. In joint capsules, especially near the surface of the synovial membrane, a marked change could be recognized. Cells appearing at an early stage of recovery were generally smaller than normal ones, and had comparatively narrow cytoplasma as compared with the large nucleus, filled with metachromatic granules; and they appeared near small vessels in loose connective tissues. Besides these, the shrinking of degranulated cells and the picture what might be thought to be granules refilling such cells could be observable. In joint capsules a new formation of mast cells was marked in deeper connective tissues, and these cells appeared earlier than in the case of the skin. That the way how the reduction of histamine contents by histamine releasers occurs and the way how its recovery takes place in the skin and joint capsules show numerically a parallel relationship with the degree of changes of tissue mast cells and their repair indicates that mast cells are the main storage of hisfamine in these tissues.
One or two mg sinomenine and 1-5 mg prednisolone injected into the joint cavity of the dog both disrupted mast cells of the joint capsule and released histamine contained in the capsule. The histamine reducing effect of sinomenine on the capsule was stronger than that of prednisolone. The ability of depleting histamine by both drugs could not bring the level down more than 10 per cent below the normal irrespective of increase in the dosage of the drugs. However, both of these drugs in an increased dose delayed replenishment of depleted histamine. Morphological differences could be observed between the mast cells destroyed by sinomenine and those by prednisolone, namely, the swelling, discrete intergranular spaces, and diffuse extrusion of granules outside the cell could be recognized in the former, while in the latter no opening of intergranular space but granules were collected into aggregates of various sizes, and these minor clusters and lumps were entwined like threads, showing a cohesive disruption, and vacuoles could be often observed. In cytoplasma of the disrupted cells in either case metachromatic tone could be observed rather than orthochromatic tone. These disruptive changes of mast cells could no longer be recognized ten days after the injection. As for the histology of the joint capsule 24 hours after the injection of either one of these drugs, slight edema and cell infiltration could be observed, but the picture ten days afterwards showed no abnormality. The relationship between the therapeutic effect of intra-articular injection of prednisolone on rheumatic or rhematoid arthritis and the action disrupting mast cells have been discussed, and it was assumed that sinomenine also may have an effect similar to prednisolone.
Several experiments on the adhesion of tenden were performed with adult rabbits, and following results were obtained. 1). Adhesion of tendon seen after removal of the paratenon was most intensive in two to three weeks. 2). The adhesion was less in the tendon preserved paratenon, which was thought to be a factor affecting the adhesion of tendon. 3). Although the adhesion was slight in the crushed tendon, for the paratenon was preserved, the fixation of two to three weeks' duration was necessary for restoration of the tendon. 4). On the prevention of adhesion the effect of wrapping tendon in living fascia or polyethylene membrane was studied comparatively. The result was better in polyethylene membrane, which prevented the adhesion perfectly. 5). It was undesirable to wrap tendon in polyethylene membrane immediately after suture or transplantation, because of its complete interception of cell permeation disadvantageous to repair of the tendon. 6). Repair of the tendon were thought to be incompatible with prevention of adhesion. It was, therefor, reasonable to intend prevention of readhesion after separation of adhesion, and best result was obtained with polyethylene membrane.
The author estimated the effect of hypophysectomy on the transaminase activity in the brain and liver of the Wister albino rat. The activities determined were aspartate-glutamate (AsGT), alanine-glutamate (AlGT), and γ-aminobutyrate-glutamate (γAGT) transaminases. The activities of AsGT and γAGT increased remarkably in the brain and liver of the hypophysectomized rat. The AlGT activity of these organs did not change under the same condition.
The author estimated the effect of ACTH administration on the transaminase activity in the rat brain and liver. The activities determined were aspartate-glutamate (AsGT), alanine-glutamate (AlGT) and γ-aminobutyrate-glutamate (γAGT) transaminases. The AsGT activities in the brain and liver of the normal rat increased by the administration of ACTH. When ACTH was administered to the hypophysectomized rat, the previously increased activities of the AsGT in the brain and liver decreased to the normal values. The ACTH administration was found noneffective on the AlGT and γAGT activities in the brain and liver of the normal and hypophysectomized rat. The author described some discussion about the difference of the effect of ACTH on the activities of the various transaminases.
The author estimated the effects of GH or Atonin-ACTH administration on the transaminase activity in the rat brain and liver. The activities determined were aspartate-glutamate (AsGT), alanine-glutamate (AlGT), and γ-aminobutyrate-glutamate (γAGT) transaminases. The GH administration was found noneffective on the transaminase activities of the brain and liver of the normal rat. When GH was administered to the hypophysectomized rat, the previously increased activites of the AsGH and γAGT in the brain and liver decreased to the normal values. By the administration of Atonin-ACTH, the AsGT activities of the brain and liver increased in the case of the normal rat, and decreased in the case of the hypophysectomized rat.
The bile secretion after a Radical operation of stomach cancer with complete removal of the regional lymphnodes was studied experimentaly in dogs with following results. 1. Cutting the coeliac nerves or the coeliac and vagus nerves was followed by decrease of secretion of bile and bile acid and absence of the effects of insulin which should promote secretion of bile and bile acid. But 3 months or less after operation these were normally secreted and insulin injection promoted normally the secretion. 2. Cutting autonomic nerves did not affect the volume of bile secretion in response to the soap in the jejunum. 3. It is considered that the humoral mechanism of bile secretion normally exists after cutting autonomic nerves, while the control of these nerves is lost. And the mechanism of nervous control recovers its normal function 3 months at most after the operation.
The external secretion of the pancreas after a radical operation of stomach cancer with complete removal of the regional lymphnodes was studied in dogs with following results. 1. Cutting the coeliac nerves or the coeliac and vagus nerves was followed by decrease of external secretion of the pancreas and the absence of effects of insulin which should promote external secretion of the pancreas. But 2 months or less after the operation it was normally secreted and insulin injection normally promoted its secretion. 2. Cutting autonomic nerves did not affect the volume of pancreatic juice secreted in response to the soap in the jejunum. 3. It is considerd that the humoral mechanism of external secretion of tho pancreas normally exists after cutting autonomic nerves, while the control of these nerves is lost, and the mechanism of nevous control recovers its normal function 2 months at most after the operation.
The effecs on digestion and absorption produced by a radical operation of stomach cancer with complete removal of the regional lymphnodes, studied by means of the patients subjected to the same operation, whose digestion and absorption was tested by Cr O ratio method. At the same time, for comparison, the same test was performed on patients subjected to simple gastrectomy and healthy men, with the following conclusion. 1. In patients after simple gastrectomy, absorption of fat and protein goes not so well as in healthy persons. 2. In patients after airadical operation of stomach cancer with complete removal of the regional lymphnodes, absorption of fat and protein is well performed as in patients after simple gastrectomy. 3. In patients after redical operation of stomach cancer and in those after simple gastrectomy, absorption of carbohydrate is carried on with almost the same rate, i. e. more than 99%, as in healthy persons.
Recently the radical operation for rectal cancer, which preserves the function of anal sphincter, is regarded as an excellent method. But from the view of its radicality there are some opinion against it. Recently to decide how much normal tissue under the tumor must be resected has become a big problem. To clarify this problem, a histological study was performed on the rectal wall under the tumor, and frequency and mechanism of retrograde spreading were investigated. 1) In specimens from 49 rectal cancers, which were resected by abdominoperineal combination method with colostomy (MILES method) and had their lower ends beyond the ampullar part, all tissues of them and the skin of anal part were cut into complete serial sections and investigated microscopically. 2) In 2 of 49 cases retrograde spread was found. 3) In one case, a successive infiltration was found mainly in muscular layer 3.5cm from the macroscopical lower end of tumor. In an other case down 1cm from the lower end of tumor at the outside of muscle layer of the rectum, lymphatic metastasis closely attached was found. 4) In both cases the primary foci and also from literatures, in the radical operation of rectal cancer keeping the function of anal sphincter, it is regarded quite sufficient if the normal colon is resected 5cm below the lower end of tumor in case the lower end of tumor lays beyond to the ampulla.
Sixty nine specimens of rectal carcinoma were classified by the author conforming to malignancy and infiltration and the relationship between them and 3 and 5 years survivor rate was studied. 1) For malignancy, it was classified into 3 grades conforming to six terms, that is infiltration figure, presence of gland cavity, unequal size of cells, quantity of chromatin and amount of mitosis. The malignancy in each term was generally in parallel. 2) For infiltration without regard to the exsistence of metastasis they were classified into 3 grades; cancer infiltration on the basis of rectal cancer which does not reach to muscle layer, which reaches into muscle layer and which goes beyond muscle layer to the outside of it. 3) According to the late results of the authors' department, the 2 years' survivor rate is 65% and 5 years' is 55%. 4) Relationship between malignancy and 3 years' survivor rate is in the I grade 100%, in the II grade 67% and in the III grade 33%. That between malignancy and 5 years, survivor rate is respectively 60%, 63% and 0%. Drawing a line on the muscle layer, the prognosis shows a big difference between that which does not reach to the line and that which spreads beyond the line. 5) The histological examination before the radical operation of rectal cancer preserving the function of anal sphincter is useful to decide the resection limit of the colon which lays near to the anal side from the lower end of tumor.
BABCOCK-BACON method and invagination method were performed to the radical operation for rectal cancer preserving sphincter function. After the operation sphincter function examined with kimographion and electromyogram. 1) Voluntary contraction relatively early recovevs after the operation. It showed almost the same contraction power after 1 month by invagination method and after 3 months by BABCON-BACON method. 2) The reflectoric contraction and fecal continence after the BABCOCK-BACON operation, recover almost the same as before the operation in 3 or 6 months. 3) From the results in histological studies on retrograde spread mentioned in part 1 and also from the examined results in this part, it could be said that the radical operation preserving sphincter function could be performed to almost all rectal cancers which posses their lower end of tumor beyond the ampullar part without any fear on radicality and postoperative sphincter function.
Sera and ascites were gained from 72 cases of gastric canser and their protein fractions were estimated. The relationship between them and the grade of metastasis which settled during laparotomy was studied. 1) The protein fraction of serum in gastric cancer patients treated in surgery clinic showed no significant difference from that of normal ones. Albumin decreased its density and ratio as metastasis proceeded. γ- and β-globulin showed an increasing tendency with the proceeding of metastasis. The former increased markedly with the proceeding of peritoneal metastasis. The γ/A ratio showed the proceeding of gastric cancer most strikely. 2) The protein fractions of ascites increased and decreased in proportion to that of serum. Albumin stood always about 10% higher than serum. γ-globulin increased with the proceeding of peritoneal metasis, while γ-globulin decreased if the metastasis advanced. In the ascites the A/G ratio never reversed. 3) The most permeable fraction was albumin and it descended in the order of γ-, β- and γ- globulin. In the advanced peritoneal metastasis, and γ-globulin were very permeable. 4) Cases in which liver metastasis was found showed high protein, low albumin and high γ-globulin. In ascites it was also similar. 5) In patient with gastric cancer, peritoneal metastasis played the leading part in fluctuation of protein fractions. There was no significant difference between lymphnodes and infilatration on the serosa of stomach and protein fractions.
Injuries were made in the brain of cats operatively and their healing mechanism were histologically studied. At the same time the convulsive threshold was estimated using provocation method by intravenous injection of metarazol and was compared with histological figures. 1) After mechanical injuries were given in the brain, mixed cleaning effects and organi zations of mesenchymal and glia systems always occured. 2) In cortex, the reaction of mesenchymal system is intensive and in medullary substance that of glia system is intensive. 3) Against the cerebral injuries, the nerve cells show the weakest resistence and the blood vessels and pia mater show the strongest resistence. That of glia cells is intermediate. 4) The healing process of cerebral injuries can be classified into degenerative necrotic stadium, granulating stadium and scar stadium according to its stadiums. 5) The cerebral injuries do not always adhere with dura. The more and deep the injuries are, less are their frequency of adhesion. 6) When cerebral injuries make adhaesive healing, the reaction of mesenchymal and glia systems is markedly stronger than that in the case without adhesion. 7) The convulsive threshold by intravenous injection of metrazol descends after operation than before operation. The more marked the adhesion is, the more intensive becomes its descending rate.
For all various studies, the making and the development of proglottids has not been known as Braun's words “die näheren Vorgänge bei der Bildung der Proglottiden sind uns bisher noch ganz unbekannt.” On cestode, we have nothing for the fundamental knowledge to the making and development of all gewebe and organe, namely, cuticle, muscle, nerve, excretoryorgane and genitalorgan. So I have observed the making and the development of proglottids of typical cestodes, Taenia pisiformis and Ditpylidium caninum since march 1941 under the kindly direction of prof. Dr. M. Suzuki. My main points of the results of the observation are as follows. 1. The fundamental mechanisms of the making and development of proglottids between Taenia pisiformis and Dipylidium caninum are completely same. 2. The making and development of proglottids of Taenia pisiformis and Dipylidium caninum is held out mainly at scorexbase and more at cervixand at first external proglottids were made, then proper proglottids developed from divisions mechanisms in those external proglottids. 3. Cuticle were made from circular cells in subcuticle celllayers, muscle were made from circular cells insiside subcuticle, fibrous tissue from cells in Parenchym. 4. Only genitalorgane wer made and developed newly in proglottids from circular cells in parenchym and subcuticle cells, but these Begining were looked erly in external proglottids and there were any difference between cells which make up cuticle and muscle of genitalorgane and cells which transform into keimcells at those form and dyeing. 5) And again I could not find any difference at form and dyeing between cells which made up cuticle, muscle, nerve fibres and cells which tranoformed into Hoden and keimstock. 6) In younger proglottids there were many those circulas cells in all tissues, but in older proglottids I could not observed these cells a few. 7) The nucleus of these cells are 2, 800-7, 600μ at Taenia pisiformis, 2, 600-4, 500μ at Dipylidium caninum in length at diameter, and coloured up violet with Hämatoxylin.
Changes of the electrolyte in the motor area of the cerebral cortex were experimentally studied in dogs during convulsions which were caused by the intravenous injection of metrazol. The results were as follows: 1) Chloride content increases at the preconvulsive stadium and also at the acme and reaches to its maximum at the repeated convulsive stadium. At the postconvulsive stadium it decreases nearly to the normal, but still remains a little higher than the normal 2) Sodium content decreases at the preconvulsive stadium and recovers gradually to the normal as the time elapses. 3) Potassium content shows no distinguished change. 4) Calcium content reaches the highest at the preconvulsive stadium and then decreases gradually to the normal as the time elapses. 5) Magnesium content at the preconvulsive stadium is the same as the normal and increases rapidly at the acme and at the repeated convulsive stadium but finally decreases below the normal. 6) From these facts stated above, it is considered that the changes of the electrolyte in the cerebral tissue during the convulsion are caused by the secondary changes due to convulsion.
The effect of Finalgon ointment, mustard plaster and other medicines on the skin and fibro-histiocytic system of subcutaneous connective tissue were investigated. 1) By application of mustard plaster and of Finalgon ointment, the skin was stimulated and showed slight inflammatory reactions, and fibro-histiocytic system of the subcutaneous connective tissue was activated, being much intensive in mustard plaster. 2) The responsiveness of the skin and fibro-histiocytic system of the subcutaneous connective tissue to mustard plster and Finalgon ointment was weakened by the repeated application in a long period of time. The skin and fibro-histiocytic system of the subcutaneous connective tissue became atrophic, and intensity of the atrophy was severer on the mustard plaster. 3) On the mustard plaster application, adjustment of stimulation dosis was difficult, but easy on the Finalgon ointment. 4) On the combinated application of Hydrocortone ointment and Finalgon ointment, the action of the latter was restrained by the former. 5) On the application of 5% hydrophilic petrolatum, the reactions of the skin and of fibro-histicytic system of the subcutaneous connective tissue was weak, being less on the application of Hydrocortone ointment.
The influence of transfusion upon brain water content after bleeding was studied. The variations of brain water content when transfused immediately, 60 minutes and 180 minutes after the acute arterial bleeding were studied in parts of cerebral cortex, cerebral marrow substance, brain stem and cerebellum. After transfusion, the water content was estimated by HATSCHEK's Cobaltum Chloratum method separately in free, bound and total water with the lapse of time, 10, 60 and 180 minutes. Results: 1) By transfusion immediately after bleeding, every part instantly shows a gradual increase of free and total water. It reaches to its maximum after 60 minutes and then continues or tends to slightly decrease after 180 minutes. 2) By transfusion after 60 and 180 minutes from bleeding, the water content increases markedly directly after the transfusion and then shows the same tendency as in the case of transfusing immediately after bleeding. 3) Comparing with normal ones, the largest variation of water content is found in the cerebellum. Marrow substance, brain stem and cortex follows. In comparison with the case in which only bleeding was occured and no transfusion performed, the largest difference is found in the brain stem: marrow substance, cortex and cerebellum follows. 4) The variation of water content is lowest when transfusion is treated immediately after bleeding. 5) There is almost no significant difference found between the transfusions given after 60 minutes and 180 minutes from bleeding. But comparing the variation of water content in cerebral cortex and cerebellum, the latter is slightly smaller than in the former. In cerebral marrow substance and brain stem, it shows an intensive tendency. 6) The increase of brain water content is always that of free water and no bound water is found, i. e. it means that it is a water increase of edema type.