1) Subjects of the present study are 49 cases with uterine cancer and one case with vaginal cancer, admitted to the Obstetrics and Gynecolgy Clinics of Okayama University Medical School during the period ranging from May 1956 to March 1957, and given irradiation therapy (Yagi-Takeda method); and observations have been carried out by the phasecontrast microscope in order to determine irradiation changes in vaginal cancer cells of these patients, using dried human serum solution as the sealing agent. 2) As the preliminary experiment, in cancer determinations on 79 patients admitted to our clinics during the period from Nov. 1955 to April 1956 and suspected of cancers, the positive percentage has proved to be 84.2 per cent, while the negative percentage to 94.8 per cent at the same time skill and invaluable experiences have been aquired for the observation of cancer cells as to ensure exact and infallible results. 3) Changes in cancer cells mainly consisted of vacuole formation, change in the nuclear membrane, loss of peripheral plasma, granule degeneration, hypertrophy, and change in nucleoles; and although a slight degeneration can be recognized already in the pre-irradiation stage, the degeneration becomes gradually more marked along with the treatment. In some, however, the degeneration disappears with hardly any change. Such changes occur in the period between 6th and 9th day after irradiation, and moreover, during the periods in which the amount of X-ray ranged from 1200 r to 2100 r, radium is not detectable. Furthermore, the degeneration disappears on the average of 25th to 26th day after irradiation and the average total dosage of X-ray at that time is 4745 r while that of radium is 3746 mgh. 4) It has been impossible to recongnize any distinct relationship between the rate of degeneration of cancer cells on one hand and the number of days required it to disappear, the tissue classification, especially the Nagase classification, age differences, differences in clinical stage and prognosis on the other.
In the determination of contents of ammonia and glutamine in the brains of normal rats and mice by Conway's method of micro-diffusion analysis, the author obtained the following results. 1) In the case of the normal mouse brain frozen and fixed in liquid nitrogen, the brain ammonia was 0.57 mg.%. 2) In the case of the normal rat brain extracted by opening the skull and frozen with dry ice acetone, the brain ammonia was 0.62 mg.%, while the brain glutaminewas 80.3 mg.%. 3) In the case of normal rat decapitated and frozen in liquid nitrogen, the brain ammonia was 1.80 mg.%, showing a quite high value. 4) In the the case where the rat, which had been exhaused by making it swim in water, and frozen in liquid nitrogen, the brain ammonia was 0.91 mg.%, showing no increase over that of the control
On determining the contents of ammonia in the brains of mice and rats at the time submitted to electro-convulsion shock with Conway's method of micro-diffusion analysis, the author obtained the following results. 1) The brain ammonia increases markedly in both mice and rats at the time submitted to electro-convulsion shocks. 2) Whereas when the electro-convulsion shock is given twice in succession, no increase in the brain ammonia can be observed. However, if the interval between the two shocks be made over three hours, the same increase as observed in section 1) can be detected. 3) When frequent electro-convulsion shocks are given for many days in succession, the content of the rat-brain ammonia decreases. and when the slices of such a brain are incubated in Krebs-bicarbonate Ringer solution, the Production of ammonia is weakened markedly.
On the determination of brain ammonia of the rats at the time submitted to insulin shock by Conway's method of micro-diffusion analysis, the following results were obtained. 1) In the case of insulin-hypoglycaemic coma, the brain ammonia of such rats decreases markedly. 2) No change in the brain ammonia occurs in the case when insulin shocks are given for successive days. However, the slices of such brains incubated in Krebs-bicarbonate-Ringer solution shows a considerable weakening in the ammonia production.
1) The effect of hepatic artery ligation is different depending on the site of ligation. A mortality rate decreases in order of the case of ligation of coeliac artery, of hepatic artery distal to its junction with gastroduodenal artery, and proximal to it. 2) Arterial circulation of the liver is relatively well reestablished through collateral vessels and adhesions after hepatic artery ligation in rat. Mortality and morbidity following hepatic artery ligation are mainly depending upon the amount of reestablished circulation. Collateral circulation is mainly developed through cappilaries along choledochus, gastrohepatic and hepatoduodenal ligaments and adhesion between the liver and the stomach, in addition to, esophageal vessels and left gastric artery are also available to it. 3) A mortality rate decreases even in multiple ligations of hepatic artery if performed in two stages. This suggests of adaptability of liver to oxygen lack. 4) Histologically, there are found degenerative changes centered the lobules in liver after hepatic artery ligation and decrease of R N A, polysaccharide and glycogen in liver cell are noted histochemically and occasionally fatty degeneration, too. Moderate degree of degenerative changes is noticeable in liver of rats who survived the experiment over the period of one to two months.
1) Incidence of mortality and morbidity following ligation of hepatic artery are less in rats in whom cirrhosis of the liver has been produced by a long-term injection of carbon tetrachloride than in normal rats. 2) Decrease of ascites and disappearance of dilatated vein occure more faster in rats with cirrhosis who had hepatic artery ligation than in control group without ligation of hepatic artery. 3) Gradual restoration of damaged liver tissue develops in both ligation group and control. Dilatation of branches of portal vein and interlobular vein, and intralobular hemorrhage are found and occasionally, marked central degenerative changes are seen in the former group. However, no difference were noticeable in degree of restoration between both groups after a given period (60 days). 4) Polysaccharide in liver cell decreases at initial stage and then increases gradually in both groups. However, distribution of polysaccharide is different between both groups when it decreases. In the control group polysaccharide are distributed scattered in lobules. However, in the rats with ligation of hepatic artery decrease of polysaccharide is more marked and temporarily disappears in most lobules except localized accmulation in some parts, and which is followed by relatively rapid increase. 5) Fatty degeneration decreases in both groups and finally disappears. Central fatty degeneration increases temoporarily and later decreases in some cases of the ligation group.
1) Various studies of urine, erythrocyte and serum have been performed following hepatic artery ligation both in rats in whom liver cirrhosis had been produced by carbon tetrachloride and in normal rats. 2) Abnormal findings found in rats with liver cirrhosis are gradually restored to normal following simple laparatomy without hepatic artery ligation. 3) Damages of the liver caused by hepatic artery ligation are detected in these studies in both rats with liver cirrhosis and normal rats. However, degree of damage is less severe in the former considering already exsistent abnormal condition before ligation of hepatic artery. 4) Rats with cirrhosis of the liver tolerate well ligation of hepatic artery indicating that they have still more reserve than minimum neccessary to keep their lives. 5) Ligation of hepatic artery has its place as a supplemental means for symptomatic relief in surgical treatment of liver cirrhosis. However, it is believed that improvement of liver function should not be expected by this method.
For the past ten years beginning with 1948 we have been using the intramascular injection of bismuth subsalicylate in treatment of 336 cases suffering from gastric and duodenal ulcers. From our experiences we believe that it is most appropriate to start with 0.5 cc of this drug for the initial injection and watching the reaction of patient carefully, to increase the dose by degree until the dose of 1.0 cc is reached. The over-all average time required and the average total dosage used for the entire group were 51.3 days and 6.16 cc respectively. However, looking over the different cases separately, the ones that showed the quickest response to the injection were the cases with duodenal ulcers in that it required on the average 36 days to recover completely and the average dosage of 4.45 cc per person; followed by the cases with ulcers of pars pylorica ventriculi and with ulcers of lesser curvature of stomach in the order mentioned. Moreover, no significant side-effects can be recognized in all the cases treated with this drug during the past ten years.
The influences of Ravonal, Procaine, Promethazine and Chlorpromazine upon the general anaphylaxy on rabbits were investigated. 1. Ravonal showed the definite inhibitory reaction upon the general anaphylaxy, which depended upon the depth of anesthesia. It did not show any marked effect in light anesthesia, while, in deep, it showed the prominent inhibitory effect. That is, the inhibitory effects varried markedly with the depth of the anesthesia. 2. As soon as the anesthetic effects reached to hypothalamus, the marked inhibitory effects were shown. This is considered to be caused by the mechanism based on the anesthetic effect on the autonomic nerve center. 3. Although Procaine showed an inhibitory reaction, the effects were slight. 4. Either Promethazine or Chlorpromazine showed the strong inhibitory reaction. 5. The excellent inhibitory effects of these phenothiazine derivatives upon the general anapylaxy are regarded to have much factors on central anesthetic reactions against the autonomic nerve system than their reactions against antihistamine and antiacetylcholine effects.
The influences of Ravonal, Procaine, Promethazine and Chlorpromazine upon the local anaphylactic phenomenon on rabbits were investigated. 1. Ravonal anesthesia as well as general and local administration of Procaine have no influences upon the manifestation of the Arthus phenomenon. This is considered to be based on their temporary actions. 2. The general and local administration of Promethazine and Chlorpromazine showed the significant inhibition to the Arthus phenomenon and their effects were shown markedly by the administration of Chlorpromazine. This inhibitory effects are considered to be based on the antagonistic actions against the accentuation of vessel permeabilities through the autonomic nerves. 3. The influences of the anesthesia and artificial hibernation upon the aquiring of the anaphylaxy were investigated by the Arthus phenomenon and the precipitin value in blood and there were no significant differences against the control. This is considered to be based on the incomplete blocking of autonomic nervous function through over the antibody producing periods. 4. Ravonal anesthesia as well as general and local administration of Procaine showed a slight inhibition to the Shwartzman phenomenon. This is, also, considered to be caused by their temporary action, but the manifestation is much earlier than the Arthus pheno menon. 5. The general and local administration of Promethazine or Chlorpromazine showed significant inhibition to the Shwartzman phenomenon. This is considered to be based on the antagonistic action against the accentuation of vessel permeability through the antonomic nerves.
The influences of the blocking of autonomic nerves by the operations upon the local anaphylactic phenomenon were investigated. 1. The inhibition of the Arthus phenomenon was made by the sympathectomy before and after the sensitization. The effects of inhibition was much more by the sympathectomy before the sensitization. This is considered to be caused by the inhibition of the antibody producing on local tissue as well as of the manifestation of the local anaphylaxy by the sympathectomy. 2. The Shwartzman phenomenon on the innervating area was slightly inhibited by the sympathectomy before the preliminary injection. This is considered to depend on the descending of the tissue reactivity by the autonomic nerve block. 3. The inhibition of the Shwartzman phenomenon was strongly made by the sympathectomy either on the control side or the blocked side before the provocating injection. This is considered to be depending on the stress based on the operation. 4. The tuberculin reaction was inhibided by the uni- and bilateral sympathicogangliecto my, in which the latter was much effective than the former. This is considered to be caused by the descending reactivity in tissue and, also, having the crossing bilateral innervation of the sympathetic nerve fibers.
Histochemical investigations were made upon the allergic reaction having the sympathectomy by means of fluorescein-labelled active protein conjugate. 1. On Arthus phenomenon at 24 hours after the provocating injection, although the fluorescence was observed in swollen connective tissue, the range of the fluorescence was narrow and weak on the operated side. This is considered to be based on the differences of the accumulated amounts of the tissue and blood antibodies. 2, The fluorescence was more instinctive and its range and strength were concentrated on the 3 rd day, but they were much weaker on the operated side than the control side. This is considered to be depending on the amounts of antibodies and, moreover, it regards to less necrotic products and weak autofluorescence. 3. The swollen connective tissue showed the coagulating necrosis and the fluorescence showed an yellow-red colour on the 7th day, and the fluorescent cells appeared at the same time. Because of the weak reaction, the fluorescent cells were much less and straggled. These fluorescent cells are considered to be the plasma cells, which concerned to the antibody production.
Attention has been paid to the mottled tooth since the report of Black and McKay in 1916. Thereafter the developing mechanism of mottled teeth has been made clear to some extent by many examinations and studies, but the majority of them is that of the permanent tooth and very few works have been made on the deciduous tooth. What these few works agree in their opinions with each other is that incidence of mottled deciduous teeth is lower than that of permanent ones, but the reason for this difference is still in the stage of speculation. The results of clinical and experimental studies on the mechanism of development of mottled deciduous teeth are described in this paper. Material and Methods: The Th-Neo-Thorin Method was used for determination of fluorine. All the materials used were distilled and only the fluorine ion was isolated. 1) Numerous cases of mottled deciduous teeth were discovered when investigation of mottled teeth had been carried out in Tomita District, Tamashima City and Konko Town in Okayama Pref. in 1953. The results obtained from the studies on the relationship between their incidence and caries of deciduous teeth and on determination of the fluorine content in drinking water are as follows: a) Average number of the persons with mottled teeth was 47.84 per cent in the permanent teeth and 15.23 per cent in the deciduous teeth, in the ratio 3 to 1. And the degree of mottled teeth was M1 in most cases and M2 in few cases and no M3 could be found. b) Minimal threshold of fluorine in the incidence of mottled teeth was approxiamtely 1.0 ppm. in the deciduous teeth, while 0.5 ppm. of fluorine caused mottled teeth ofdegree of M1. c) Caries incidence of the deciduous teeth was as low as that of the permanent teeth; and caries incidence in case of mottled deciduous teeth was lower than that in case of permanent ones. 2) The following experiments were performed for the purpose of investigating the rôle the placenta played in the fluorine metabolism during pregnancy: First, the fluorine content in the placenta of pregnant women and in the drinking water taken by them selves during the pregnancy were determined both in fluorine and non-fluorine districts. Then oral examinations of the children of the mothers in the fluorine district were conducted. And the rationship of incidence of the mottled deciduous teeth to the content of fluorine in the placenta and in the drinking water was investigated and the fluorine content of the deciduous teeth was determined at the same time. The results obteined were as follows: a) When the mother took a large amount of fluoride, some of fluorine was retained in her placenta, while the rest pessed through the placenta and had an effect on the embryo. b) The higher was the content of fluorine in drinking water, the larger was the amount of fluorine retained in the placenta. c) A small amount of fluorine could be recognized in the control placenta taken from the non-fluorine district. d) Incidence of mottled deciduous teeth was dependent upon the fluorine content of drinking water. e) The larger the content of fluorine in drinking water, the more frequently seen the incidence of mottled deciduous teeth with its minimal threshold of 1.0 ppm. f) Fluorine of 334.4 ppm. on average was contained in the mottled deciduous teeth, i.e. about one third of fluorine in the mottled deciduous teeth. 3) The following animal experiments were performed in order to confirm those results mentioned above in human: Rabbits were used as experimental animals to investigate what amount of fluorine was retained in the placenta and to what extent it was transmitted to her embryo and, moreover, to determine whether there was any limit in the retention of fluorine within the placenta.
Comparison was made between the blood pictures of nutritional vein in the femur and of femoral artery following irrigation of fresh extract of cancerous tissue obtained from stomach cancer. Although, no significant fluctuations were encountered between them in short period after irrigation, it was observed that a marked decrease (27%-30%) of red blood cells in the nutritional vein after more than three succeeding irrigations daily. In the other hand, a slight decrease (12%-13%) of red blood cells was observed in femoral artery blood. The fact shows that the cancer toxin directly affected bone marrow gains anemia-producing action after circulating the body, which is followed by so-called blood cell “Sperre” in bone marrow. Red cells decrease noticeably in nutritional vein of bone marrow by irrigation with sera obtained from stomach cancer patients, showing a peak of decrease one to two hours and restores to preexperimental level after six to eight hours. The same result is noticeable regarding to the leucocytes but its Schilling differentiation is not significantly changed. Serum of healthy man does not produce above-described effects on bone marrow by irrigation. Serum of anemic rabbit produced experimentally by successive injection of cancer extract decreases red cells in the nutritional vein following irrigation into normal rabbit marrow.
It has been confirmed by many authorities that the liver and spleen play an important role on production of anemic-factor in development of anemia by various agents. However, no studies are found regarding cancer toxin. To disclose the anemia-producing action of cancer toxin an experiment irrigating the liver and spleen by extract of cancerous tissue obtained from stomach cancer has been performed. No significant fluctuations between the blood pictures of portal and hepatic veins following irrigation of cancer extract into the portal vein of rabbit is noticeable. Serum of hepatic venous blood obtained during lirer irrigation by cancer extract produces decrase of red cells (12.9%-14%) in nutritional vein by one to two hours irrigation into femur marrow of normal rabbit. The same result is obtained in the case of spleen irrigation, too. It will be believed, after all, that the liver and the spleen form anemia-producing substances by influence of cancer toxin and they play significant roles on develo-pment of anemia in cancer patients.
Although, it is easily understandable that cancer toxin directly affects bone marrow, most studies have been done in vivo up to date. To clarify mode of normal and pathological physiology of the bone marrow culture of bone marrow has been performed on rabbit and influence of cancer extract on the marrow has been studied. The growth area, cell density, migration velocity and shape and form of growing cells were observed after adding cancer extract obtained from stomach cancer and normal gastric mucosa extract as a control. On cancer extract both the growth and migration velocity of cells were markedly surpressed comparing to the controls.
I have conducted an experiment, first, by classifying some rabbits into two groups, one, of complete hunger, another, of incomplete hunger, being administered every day such as water, glucose, vitamin B1, olive oil and water, alcohol, as well as methionine; and then, by using Tiselius' electrophoretic apparat, examined those changes that occur to serum protein fraction, by administering mononutrient, and at the same time examined about the blood changes; by which arrived at the following results: 1. It is methionine that has proved most to prolong the living days; next, alcohol, and then, water. 2. The degree of decline in weight has proved highest in proportion to the length of life time. 3. The number of erythrocytes and haemoglobin quantity has proved about parallel; it has shown some increase under perfect hunger, while, certain decrease or no great change in incomplete hunger. 4, As for the leucocyte number, there were those that have proved a slight increase, or on the contrary, those that have proved certain decrease. 5. As to the total blood nitrogen amount, no great change found in both groups of hunger. 6. The rest blood nitrogen showed a general increase in almost all experimental groups. 7. In every experimental group, the quantity of blood sugar proved either to increase violently before death, or to increase through the whole period of experiment. 8. As to serum protein quantity, it has shown a slight decrease in water given group, a slight increase in methionine-given group, but anyhow no great change found. 9. The serum albumin, whether in perfect of in imperfect hunger, proved somewhat to tend to decrease. 10. Serum α-globulin proved some increase in almost every case. 11. Serum β-globulin, proved certain differences in each group, but no great one. 12. Serum γ-globulin proved to increase remarkably in each experimental group where either methionine, alcohol, or glucose were given. 13. From the electrophoretic observation of serum protein fraction, it has been discovered that for the mononutrient which serves to maintain as well as improves albumin which is principal body protein aud α-globulin which represents antibody protein, glucose stands most efficient; then methionine and alcohol.
The author studied the influences of the storage conditions on the immunogenicity of the vaccine of Rickettsia tsutsugamushi. The formol vaccine was prepared from the ascites of the guinea-pigs previously injected with chlorpromazine and then intraperitoneally inoculated with R. tsutsugamushi. The results are summarized as follows: 1) By the storage at 4°C, the immunogenicity of vaccine is well preserved for about 1 year. After 1.5 year, however, it is markedly diminished. 2) By the storage at room temperature, 15 to 25°C, the immunogenicity of vaccine becomes very unstable and is markely diminished after 3 months.
It was previously reported by the members of the author's laboratory that the ascites of the guinea-pigs previously injected with chlorpromazine and then intraperitoneally inoculated with Rickettsia tsutsugamushi had a high degree of immune effect. In the present experiments, the distribution of the immunogenicity of the ascites was studied. The ascites was divided into 4 fractions, purified rickettsiae, cellular component and ascites serum, ascites albumin, ascites globulin and the rest components. The immunogenicity was the highest in the fraction of purified rickettsiae, and the next in those of cellular component and ascites serum and of ascites albumin, whereas the fraction of ascites globulin showed no noticeable immune effect.
In the course of our cleaning for about one year in the past we have used Miltown, one of tranquilizers on the total of 53 cases of various mental diseases, treated in our clinics either as outpatients or inpatients. As the results, out of 14 schizophrenics not one showed complete remission and the number of patients showing no effect whatsoever reached as much as 8 cases. In contrast to these, remission could be observed in four out of 9 manic-depressive psychoses; and likewise in other cases such as cases with nervousness, neurosis and psychogenic reaction, the remission rate proved to be considerably high. A slight soothing and transient improvement has been observed in one each of the cases of Parkinsonism and spinal spasmatic paralysis. Furthermore, a large dose of this drug used for a long period of time did not show any marked side-effect.
By conducting a series of tissue culture with bone marrow obtained from mammals (mice, albino rats, guinea pigs, cats and dogs), birds (chicken and pigeons), and cold blooded animals (frogs) the author studies the rate of tissue growth and wandering cells, and obtained the following results. 1) As for the growth area, the explant in culture grows up to 72 hours in the cases of albino rats, guinea pigs and cats, while in the case of other animals the growth continues almost up to 48 hours. However, in the case of mature dogs the growth ceases within 24 hours, and the relative growth in the cases of mature dogs and frogs presents a marked decrease. 2) In comparing the index of the cell density at the 24-hour culture, it is markedly lower in the cases of dogs and frogs, whereas in other animals it is over 50. 3) Myeloblasts, promyelocytes and myelecytes of all these animals have no active wandering capacity, and at the stages of maturation later than metamyelocytes cells show the wandering capacity. Neutrophils and pseudoeosinophils show the most active pseudopoid movement. 4) As for the wandering capacity of basophilocytes, the lower the species of animals the poorer is their wandering capacity. However, as for the wandering capacity of eosinophils, lymphocytes and monocytes no marked difference in the wandering capacity can be observed among different animals. Motility of thrombocytes can be observed and moreover, even in species lower than birds, a slight pseudopoid movement of spindle cells can be recognized. 5) Comparing the wandering velocity of neutrophils and pseudo-eosinophils of various animals, with exception of dogs that show generally a decrease, no marked difference in the maximum wandering velocity among them. As for the duration of wandering, with one or two exceptions, generally the lower the species the shorter is the duration. 6) In comparing various plasma such as those of dog, man, rabbit and chicken as the medium for bone marrow culture of the dog, dog plasma gives the best relative-growth value as well as the highest wandering velocity of neutrophils.
With bone-marrow tissue culture of such various animals as mammals (mice, albino rats, guinea pigs, cats and dogs), birds (chicken and pigeons) and cold blooded animls (frogs), the author studied the phagocytosis of carbon particles by bone-marrow cells and obtained the following conclusions. 1) In the neutrophilic series myeloblasts, promyelocytes and myelocytes show no phagocytic power. Metamyelocytes of mammals show a sligh phagocytic capacily; but it is wanting in the species lower than birds. On the other hand, mature neutrophils show a considerable phagocytic power. 2) Eosinophils, basophilocytes and lymphocytes have no phagocytic capacity nor megakaryocytes, but thrombocytes possess adhesive and phagocytic abilities. A slight ingestion of carbon particles by spindle cells can be observed in the species lower than birds. 3) Comparing the average rate of phagocytosis of mature neutophils, it is generally higher in mammals, followed by that of frogs, and it is lowest in pseudo-eosinophils of birds. 4) The phagocytic ability of monocytes increases along with the lapse of time, surpassing that of neutrophils, and it does not decrease even with the passing of time. Moreover, the average rate of phagocytosis of monoytes shows no significant difference among various animals as observable in the case of neutrophils.
With bone-marrow tissue culture of various animals, namely, mammals (mice, albino rats, guinea pigs, cats and dogs), birds (chicken and pigeons), and cold blooded animals (frogs), the author studied neutral red vital staining of bone marrow cells and arrived at the following conclusions. 1) In the neutrophilic series, granules of young immature cells have a strong affinity to neutral red, and mature neutrophils are stained in intermediate degree. The stained granules tend to fuse with one another and grow larger alog with the lapse of time. 2) Practically all eosinophils are stained light red, while basophilocytes are all stained deep red. Eosinophils of birds show some reluctancy to be stained. Monocytes on the whole are stained in intermediate degree and they are usually arranged in the rosette formation and those in birds and frogs are arranged in a typical fashion, Lymphocytes, megakaryocytes thrombocytes and spindle cells all clearly show neutral red granules. 3) As for the stainability of neutrophils and pseudo-eosinophils with respect to the passing of time in birds, it is generally highest in pseudo-eosinophils and also the average rate of staining is higher than that of mammals, but their color fades more quickly. In neutrophils of frogs the rate of this color-fading is rather slower than that of warm-blooded animals.
In the determinations of glutamic acid, glutamine, γ-aminobutylic acid, and aspartic acid in the rat brain by paper chromatography, the author obtained the following results: 1) In the normal rat brain, the value determined for glutamic acid was 158.4 mg.%: for glutamine 95.5 mg.%; for γ-aminobutylic acid 35.2 mg.%; and for aspartic acid 30.8 mg.%, respectively. 2) After the convulsion caused by electro-shock, the contents of glutamic acid and γ-amino-butylic acid in the brain showed a decrease. 3) In the animals treated with electro-shocks for 13 to 18 days (2 times/day), the content of γ-amino-butylic acid in the brain decreased, while that of glutamine an increase, and aspartic acid increased markedly. 4) During the coma caused by insulin shocks, the content of glutamic acid showed a decrease, while that of glutamine an increase, and aspartic acid increased markedly. 5) In the group given repeated insulin shocks, glutamic acid drecreased while glutamine increased; and aspartic acid increased markedly.
In the determinations of the content of free ammonia in the rat brain by Conway's micro-diffusion method, and that of free amino acid by paper chromatography, the author obtained the following results. 1) During the marked excitement caused by 20% caffeina et sodii benzoas injections (0.5cc per dose), the content of ammonia increased while those of glutamic acid and glutamine decreased. 2) During the deep sleep caused by amobarbital injections (50mg/kg), the content of ammonia decreased, whereas those of glutamine and aspartic acid increased.
In the case of meprobamate application and reserpine injection as tranquilizing treatment, the content of ammonia in the brain was determined by Conwy's micro-diffusion method while that of amino acid by paper chromatography; and the following results were obtained: 1) After meprobamate application per os (1g. per dose), the contents of ammonia. glutamic acid and γ-amino-butylic acid decreased, while those of glutamine and aspartic acid increased. 2) In the group given meprobamate for successive days (350 mg-400 mg/kg), the content of ammonia increased, whereas those of glutamic acid, glutamine, γ-amino-butylic acid and aspartic acid less markedly. 3) In the case of reserpine injection (0.4 mg./kg), ammonia decreased markedly and glutamic acid and γ-amino-butylic acid less markedly. 4) In the group receiving reserpine injections for successive days (0.025 mg/kg/day), the content of ammonia showed a decrease, while that of aspartic acid an increase.
Globus pallidus, putamen and the adjacent part of internal capsule, head of caudate nucleus and lateral part of thalamus were surgically destroyed in cats, and degeneration of nerve fibres was seen in the internal capsule, cerebral peduncle, thalamus, espcially lamina medullaris externa, stratum reticulatum thalami, ansa lenticularis, pedunculus thalami inferior, corpus Luysi, Darkschewitsch' nucleus, Cajal' interstitial nucleus, radiatio tegmenti, brachium colliculi caudalis, Forel' and Meynert' decussation, bilateral red nuclei, tractus tegmenti medialis, fasciculus praedorsalis, substantia nigra, lemniscus medialis, stratum fibrosum pontis etc. Eleven parts were selected for investigation among these parts of degeneration, i.e. capsula interna (or pes pedunculus cerebri), lamina medullaris externa, pedunculus thalami inferior, stratum reticulatum thalami, rediatio tegmenti, nucleus ruber minocellularis, nucleus ruber magnocellularis, lemniscus medialis, brachium colliculi caudalis, substantia nigra, and stratum fibrosum pontis and the diameter of the nerve fibres of these selected parts was measured. Most of the fibres are thicker and the mean diameter of these parts are ranged in the following order from the thicker to the thinner: capsula interna (or pes pedunculus cerebri), nucleus ruber magenocellularis, lemniscus medialis, brachium colliculi caudalis, lamina medullaris externa, nucleus ruber minocellularis, stratum fibrosum pontis, pedunculus thalami inferior, radiatio tegmenti, stratum reticulatum thalami and substantia nigra. The extrapyramidal nerve fibres are mostly thinner than the pyramidal ones in these parts. When the thickness of the nerve fibre of the peripheral and spinal nerves reported in literature, the peripheral nerve fibres are the thickest and those in the brain are the thinnest and a marked difference between them is oberserved.
The liver tissues of the healthy guinea pig and the guinea pig given a carbon tetrachloride or colloidal argent were effected with the bile of rabbit and we observed the prosperity and decay of the bile pigment in the bile and the cutting piececs of the liver tissues. The results are as follows: 1) The color of the bile gradually becomes changing a greenish yellow from a green through a yellowish green since one hour after the bile was effected with the liver tissues of healthy guinea pigs, but it is uchanged after 3 hours and the density of the bile is slightly decreased. At that time, the liver tissue is dyed and it's density becomes increased time by time, and the color is the same with the prosperity and decay of the bile, but the pigment is not reached over the 4 or 5 layers of the cell. The change of the color to yellow may be caused by the reduction to bilirubin from biliverdin according to the Gmelin reaction. The hematoidin cristal and granula in the edge of the liver cells around the liver aciuus, a part of the star cells and of the Glisson's capsules become appeared at the second hour, and they are decreased time by time after the third hour. Since the above observations, the transfer of the bile pigment into the liver tissue is not caused by a dye but it seems to be caused by a active absorption and it seems to become thickened. 2) The yellow color become strong more faster, and the appearance of hematoidin reaches into the central area of the acinus widely, as added sodium lactic acid into the bile prior to the expriments. 3) In the cases using of the liver tissues obstructed with a carbon tetrachloride, the dying condition of the tissues is the same with the normal cases, but the yellowish change of the bile and the dying pigment of the tissue is depressed and the reduction of biliverdin to bilirubin seems to be prolonged. And the hematoidin cristal and granula also do not appear in the regions described previously. 4) In the cases using of the liver tissues with the obstruction of the reticuloendothelial sysem, the dying condition of the liver tissue is the same with the normal cases, but the yellowish change of the bile and the dying pigment in the liver tissue is not observed, and the appearance of the hematoidin cristal and granula also is not observed.
I have observed the prosperity and decay of the dehydrating enzyme of lactic acid in the liver tissues of the healthy guinea pigs, the guinea pigs with the use of carbon tetrachloride and the guinea pigs with the obstruction of the retieuloendothelial system without any preparation and with the effection of the rabbits' bile. The results are as follws: 1) The liver tissue of the healthy guinea pig works to fade methylene blue and the process of the discoloration is more promoted by the addition of Sodium lactic acid. 2) Even though it's action become markedly decreased, the surface of the liver tissue of healthy guinea pig effected with the bile has the reducting action of methylene blue and it's action become promoted by the addition of sodium lactic acid, but the reducting action become low by the process of the times which the liver tissue was effected with the bile. At that time, the decline of the methylene blue reducting action at the surface of the liver tissue, it comes up to the 3 or 5 layers of the cells in depth. 3) The same condition is observed on the liver tissue of the guinea pig with the use of carbon tetrachloride and the obstruction of the reticuloendothelial system, but comparing with the healthy case, the reducting action of methylene blue become markedly weak. And comparing between the above two cases, the reducting action of the later is more weak than the former. Therefore, the effect to the reducting action of methylene blue by the effection of the bile is not shown clearly. 4) The report of Dr. Horio in our department that the activity of the dehydrating enzyme of lactic acid become decreased in the cases with the function impediment of the reticuloendothelial system, is adequate. 5) In the cases of the liver tissues effected with the bile, the decreased process of the dehydrating enzyme of lactic acid at the surface of the cutting tissue of the liver is in parallel with the reduction's process of biliverpin to bilirubin in the bile and the tissue and the dehydrating enzyme of lactic acid working on it is only the enzyme on the surface of the cutting tissue of the liver.
I have observed the activity of the dehydrating enzyme of lactic acid at the surface of the liver tissue and the prosperity and decay of mitochondria after shaking the cutting tissue of the liver with the physiologic saline solution, the bile and the natrium choleric acid solution into the physiologic saline solution. The results are as follows: 1) The activity of the dehydrating enzyme of lactic acid in the tissue is not influenced within four hours on the shaking of the liver tissue in the physiologic saline solution. 2) The activity of the dehydrating enzyme especially the dehydrating enzyme of lactic acid become depressed, as the density of the choleric acid natrium solution reaches over a certain level and the acting time is prolonged, on the shaking of the liver tissue with the natrium choleric acid solution into the physiologic saline solution, but it is markedly lighter than that by the bile. At that time, there is not any difference between the sodium glycocolic acid and the sodium taurocholic acid. And the fall of those enzymes activities remained at the 3 or 4 layers of the liver cells in depth. 3) The remakable fall of the enzymes activities by the bile is partly associated with the obstructing action by the natrium choleric acid, but it seems to be mostly caused by the reduction of biliverdin to bilirubin at the inside and outside of the tissue. 4) The liver cells at the surface mades a degeneratien by the process of times, the mitochondria changes the form, the movement of the brown becomes dull and then disappears on the shaking of the liver tissue with the phyiologic saline solution, but this process makes promoted by the use of the natrium choleric acid solution into the physiologic saline solution and it become the most high and fast by the bile. Since the aboves, it can be said that the choleric acid acts to the mitochondria of the liver cells and gives a influence to the activity of the enzyme.
Since Iversen, P. and Rohom, K. attempted the liver-biopsy and reported that it was a valuable method to make the diagnosis of liver-diseases in 1939, the liver-biopsy has been used for making the diagnosis of liverdiseases. But one scholar described that the patho-histologic findings of the liver on liver-biopsy are not just same with those on autopsy. For the purpose to find the degree of the above differences, I made the acute and subacute liver damages in dogs with the subcutaneous infection of Allyl formate, and studied the biopsy-findings and autopsy-findings of the liver. And I found the following resultes: 1. The biopsy-findings of the acute and subacute diffuse changes in the whole liver agree with the histological findings of the autopsymaterials at the early stage of death. It is thought, especially, Disses space is not the artificial product from the liver-biopsy and the pathologic studies on it are necessary. 2. The tissues from the liver-biopsy are so small that the observation of the Disses apace and the determination of the blood volume in it are occasionally difficult. But it can be supplied the deficiency of the biopsy to use the methodes for silver impregnation and other stains and the completion of the continual pieces.
It is not entirely agreeable with the serous inflammatory put forward by Eppinger, H. as the Onchopathology of epidemic hepatitis. Making clear the point described the above, the author examined both the material from the autopsy and from the liver biopsy on epiemic hepatitis especially about the Disses space of the liver, the foundation of serous inflammatory, and made clear its pathological significance. The results are as follows: 1. By the autopsy, the Disses spaces dilatation was observed in the whole parts of liver acinus, and we also observed the serous exsudation dying equally to Eosin. variously to Anilinblan, deeply and irregularly or nodularly to Anilnblan and in which deposited the substance dying gray white, frown or black to Bielschowsky-Pap, and the extra vasation of red cell, also the existance of aksquamated cell. A certain relation was observed between the size of Disses space and the degree of parenchyma damage. 2. The dilatation of the Disses space was not so distinguishable on the material of liver biopsy, but its dilatation was more or less observed in the whole parts of acinus by earful observation, especially, the same substances as depositedin the liver from autopsy were observed at the same place on the cases with the unclear dilatation of Dissea space. And the finding is inclined exactly to follow step and tide of disease, and the material become fibrosing and the wall of vessels become thickining with the chronic process of diseases. 3. The above findings show the meaning of the pathological significance of Disses space, and it proved the introduction of Prof. Yamaoka that the remarkable findings are seen in the vascular system of epidemic hepatitis with the dilatation of central vein in the liver-lobules and in lymphatic space.
Eppinger, H. tried to endorse the inflammatory theory with the experimental of allyl formate, but there are not a few scholar expressed their opinions against the theory and also same differencies on Disses space are foung between autopsy and biopsy. Under the above sence, I studied histologically on the influence of DOCA using for epidemic hepatitis. 1. Searching mainly for the variation of Disses space on the dog's liver leaving at the room temperature, is not clearly shown in a short time, but it is clearly shown after 3 hours and it is remarkably observed after 24 hours. As for its living wall, it is mostly void but a light flocculatise substance is sometimes observed in it. Therefore, the general theory that Disses space being clear by the changeness after death night be agreeable. We, therefore, must accept the general theory, which the Disses space become clear by the changeness after death, put forward by many scholars. 2. Leaving the dog's liver toxicated by allylformate at the room temperature, the dilatation of Disses spaces is observed as same as the healthy one. On the other hand, observing closely for the fresh tissues, it is possible to observe the Disses space, and the serous exsudation and the imperturbability of homozeneaus substance or brownish blue granular material are found at the same place. But the dgree of it is not as clear as the one found in the liver of epidemic hepatitis. 3. Making the allylformate toxication on dogs, the expansion intermediate and the atrophy of the liver cells with the vacuolar dgeneration in a part or zones and peripheral zones vacuolar are observed, and the capillary vessels are remarkably limited, interrupted and partly obliterated and staynative hyperemia is fouud. 4. If DOCA is given to the dogs, at that time, the above changes are improved according to the dosis. The degeneration of the liver parenchym is light with a small amount of DOCA, and the capillary vessels is normal or becomes a little narrow, and it is not observed even a little with the big dosis and the capillary vessels is rather dilated and the blood circulation is increased. 5. It is, therefore, clear that the influences of DOCA on the dogs toxicated with allyl-formate is remarkable and DOCA acts upon the vascular system and improves the changes of the liver parenchyms.
1) Dogs were killed through three different ways: rapid intravenous injection of ravonal, cutting the abdominal aorta and heart block. The water content of the lungs was almost the same and independent of the procedures adopted. Between the right and left lungs no difference of water content was detected. 2) To evoke pulmonary edema ligation of the pulmonary lobe vein, injection of veratrin to the cystern, and pericardial tamponade to dogs with hypoproteinemia were performed. By the first and second only histological pulmonary stasis was made. However, by the last, both pulmonary stasis and edema could be developed. 3) The extent of the stasis was slight in the group of the ligated vein considerable in that of veratrin injection to cystern, and highest in that of pericardial tamponade. In 56.3% of this group fluid retention was observed in the alveoli. 4) The water content of the lungs was nearly parallel to the extent of stasis. The content increased markedly in the animals with pulmonary edema. Even in the animals with effusion in the alveoli, if the stasis was slight in extent, the water content increase was not significant.
To examine whether anesthetics have to do with the development of postoperative acute pulmonary edema, dogs were anesthetized with either ravonal, ether, cyclopropane, nitrous oxide and ether+hypotensive anesthesia and the water content of the lungs was measured after two hours. The results obtained were as follows: 1) When ravonal was intravenously injected during the respiration under the atmospheric air, the water content of the lungs increased slightly in comparison to the control. This is not to be ascribed to the direct action of ravonal but to anoxia and hypercapnia due to the inhibited respiration. 2) When closed circuit endotracheal anesthesia was performed under inhalation of pure oxygen, with any anesthetic, the water content of the lung did not vary and stayed within the standard deviation of the control.
To see influence during controlled respiration and anesthesia with the openchest the water content of the lungs, dogs were anesthetized with ether. 1) By unilateral opening of the chest the water content increased in both lungs. However, the extent was slightly highere in the opend side. 2) When a muscle relaxant was administered and controlled respiration was performed without opening the chest, the water content of the lungs increased only within the standard deviation of the control. 3) When controlled respiration was performed under unilateral opening of the chest, the open chest showed no influence upon the water content. 4) A simple unilateral opening of the chest evoked slight, macroscopic stasis in the lungs. In the animals on which controlled respiration was performed, almost no change was observed and the opening of the chest showed no effects.
To dogs anesthetized with ravonal low oxygen gas was given or accumulation of carbon dioxide was evoked. After that the influence on the water content of the lung was observed and the following results were obtained. 1) In the group to which pure oxygen was given during ravonal intravenous anesthesia, the water content of the lung showed little less than the control. 2) In the group air or 15 vol. % oxygen was given, the water content increased though slightly in degree. The increase was more marked with the latter. 3) With 10 vol. % or 5 vol. % oxygen, the water content of the lung increased markedly. However, in the group inhaled 5 vol. % oxygen than in that with 10 vol. % oxygen, the degree of increase was slighter, because the animals died in the relatively early stage. 4) By carbon dioxide accumulation, too. the water content of the lungs increased markedly. From the above stated data, anoxia and hypercapnia are the most important causes for postoperative acute pulmonary edema and closed circuit anesthesia is often accompanied with the both complications.