The direct effect of ACTH on brain tissue not by way of adrenal glands is suggest by the fact that ACTH has a remarkable therapeutic effect on vairous diseases of nervous system such as japanese encephalitis.
The first part of the present report is concerned with statistical observation of therapeutic effect of ACTH on patients with nervous diseases.
1) ACTH was effective in 70 per cent. The effect was especially marked in Parkinson's syndrome, japanese encephalitis and chorea minor.
2) As for symptoms, disturbance of consciousness, fever, involuntry movements and mucle rigidity were successfully treated by ACTH.
3) In intracranial bleeding and thrombosis too, ACTH showed a good effect on loss of consciousness, motor disturbance and dysarthria in a decreasing order.
The second part is concerned with observation of therapeutic effect of ACTH on brain edema of adrenectomized dogs. Degree of edema is calculated by the amount of RIHSA measured in the brain.
1) In the control, index of brain edema (amount of isotope of brains cortex of the thrombosed side/that of the contralateral normal cortex) was 15.6
2) In dogs removed of adrenal cortex & treated by ACTH, index of brain edema was 6.4.
The above results indicate that ACTH has a dirct effect, not by way of adrenal cortex.
It is clarified, however, whether this effect is a direct on brain tissue or by an enhancement of coricosteroid effect.

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The first part of this report is concerned with on effect of ACTH in vivo on chronic brain edema. Brain edema was produced by ligation of the carotid artery and the dog was killed by scaffold 3 days after removal of adrenal gland and ACTH-Z injection. Respiration and anaerobic glycolysis of the brain was examined by Warburg's direct method.
1) The group with the carotid artery ligated showed lower Qo₂ and Q_M^N2 than the control group.
2) In the group with the carotid artery ligated, and ACTH injection resulted in higher QO₂ and Q_M^N2.
3) The group with the carotid artery ligated and bilateral adrenal glands removed showed higher QO₂ and Q_M^N2 than that with the artery ligated, and showed no difference from the control.
4) Ligation of the carotid artery, removal of the bilateral adrenal glands, and ACTH-Z injection resulted in higher QO₂ and Q_M^N2 than the ligation alone or no treatment.
The above results indicate the existence of direct effect of ACTH which decreases brain edema and increases expiration of brain tissue.
This in vivo experiment, however, did not clarify whether the effect was a direct one of ACTH or just an enhancement of corticosteroid effect.
The second part was concerned with an in vitro experiment. An influence of ACTH on respiration and anaerobic glycolysis of brain cortex of normal mice was examined by Warburgs method. An addition of 1.0u/cc of ACTH resulted in a mild depression of respiration and enhancement of anacerobic glycolysis. No influence was observed in the other group.
The whole results indicate that ACTH injection results in an enhancement of corticosteroid effect on blood-brain-barrier, not by stimulation of adrenal cortex but by itself, althrough the direct effect of ACTH on the barrier is not cempletely neglected.
It seems correct to conclude that ACTH a defentive effect on blood brain barrier and on the production of brain edema by way of an enhancement of corticosteroid effect.

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1) On the simplification of the splenic tissue culture, the author studied the influences of the various serums and growth promoting substances upon the splenic tissue culture of mice, rabbits and rats.
2) Culturing these spleens with the unactivated serum or untreated serum, the author concluded that the splenic culture with the unactivated serum was superior to the latter in all data of cultures.
3) Culturing these spleens by adding vitamin B₁₂, folic acid or nucleic acid, which were on the market, for the growth promoting substances, both in mice and rats the cultures adding vitamin B₁₂ showed comparatively excellent growth, and in rabbits the cultures adding folic acid or vitamin B₁₂ showed somewhat good growth, between which significant difference was not shown.
4) On the basis of these results we called the following method the clinical tissue culture method of the spleen, in which the spleen was cultured in the medium composed of unactivated serum and vitamin B₁₂ (100^γ/^C.C.) using the Hiraki's tissue culture slide No. 1, and then the data using this tissue culture method was compared with those obtained by the conventional plasma clot culture method. These results showed that, although this method was slightly inferior to the plasma clot culture method in the data of cultures, it was sufficiently fit for clinical application.

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1) The author observed the influences of osmotic tension upon the clinical tissue culture of mouce's spleen. In the hypotonic medium, although the rate of relative growth was higher than in the isotonic medium, the cell density was lower and in the wandering velocity of lymphocytes no significant difference was shown. In the hypertonic medium the rate of relative gromth, the index of cell density and the wandering velocity of lymphocytes were lower than in the normal medium.
2) The author observed the influences of temperature upon the clinical tissue culture of mouce's spleen. The most suitable temperature to culture was from 35°C to 37°C, and the range of temperature in which culture was possible was from 25°C to 39°C. At 33°C and 35°C the progress of degenerative process was delayed.
3) In order to observe the influences of hydrogen ion concentration of media upon the clinical tissue culture of mouce's spleen, the author cultured by adding the various concentration of hydrochloric acid or sodium hydroxide in the medium. In acid medium the growth was possible even by adding 1/100N hydrochloric acid, and in alkaline medium the culture was possible even by adding less than 1/500N sodium. hydrox ide. All the rate of relative growth, the index of cell density and the wandering velocity of lymphocytes, except the rate of relative growth in the medium adding 1/1000N hydrochloric acid, were lower especially in high concentration of acid or alkali than in the control medium adding physiological salt solution.
4) According to these results in the clinical tissue culture of spleen, except relatively lower temperature, it was shown that unphysiological physicochemical conditions suppressed or stimulated the growth of tissue culture and were harmful to culture.

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The author employed securely laparoscopy in performing direct vision splenic biopsy, cultured the biopsied human splenic tissue using the clinical tissue culture method of spleen, and obtained the following conclusions.
1) In the lighting observation of spleen using laparoscopy, about half the number of both leukemia and Banti's disease showed change in the character of surface, namely, color, hardness, enlargement, atrophie, unevenness and adhesion. In the histological observations of biopsied splenic tissue, although all cases of lekemia showed the infiltration of leukemic cells, the determination of infiltrated cells in an acute lymphocytic leukemia and two cases of monocytic leukemia was difficult. In adout 70 per cents of Banti's disease the histological observations which suspected this disease were shown. In the splenogram of all cases of leukemia, the infiltration of various leukemic cells was seen respectively, and the determination of infiltrated cells was possible. While in the splenogram of Banti's disease no significant pathological findings were obtained.
2) In the splenic tissue culture of acute leukemia including monocytic leukemia, the boundaries of the growrh zone were well-defined and clear-cut, the cell density increased markedly and cells in the growth zone were mostly lymphoblasts and young lymphocytes in the case of acute lymphocytic leukemia, myeloblasts and immature granulocytic cells in the case of myelogenous leukemia, and monoblasts and promonocytes in the case of monocytic leukemia.
3) In chronic myelogenous leukemia double growth zone was not shown but the similar pattern to that of acute leukemia was seen.
4) In leukemoid reaction the pattern of splenic tissue growth was similar to that of normal human spleen, however in the growth zone numerous myelogenous cells, many of which were immature, were seen.
5) In Banti's disease the growth was somewhat reduced. In the terminal stage, splenic reticulum cells and fibroblasts tended to increase.
6) In aplastic anemia the growth pattern was similar to that of normal spleen, howevrer a few immature myelogenous cells were always found in the rowth zone.
7) In chronic Werlhof's disease the growth pattern gshowed that of normal spleen, except that many megakaryocytes with diminished function appeared in the growth zone.
8) In leukemic reticuloendotheliosis the growth pattern resembled that of acute lekemia. The growth zone was composed of the same lymphoblastoid cells as found in the peripheral blood and larger young cells.
9) In infection the growth pattern resembled the normal but its growth was remarkable and mature neutrophils were increased markedly.
From these results the author thought that the clinical tissue culture method of spleen, when it was performed in company with the clinical tissue culture method of bone marrow, had important clinical significance for making clear various blood diseases and other diseases mit splenomegaly.

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For the purpose to study changes in the compostion of the long-chain fatty acids induced by a relatively minute quantity of ³²P-radiation of the body, 500 μCi/kg of Na₂H³²PO₄ were injected intravenously into normal rabbits and the internal organs and the serum were taken out at intervals of 24, 48 and 72 hours after the injection, and studied the composition by means of gas-chromatography. The results are briefly summarized in the following.
1. As the result it was found that the distribution of ³²P in the organs was in the descending order of liver→kidney→spleen→bone marrow.
2. The fatty acid composition in each of these organs as well as in the serum is affected by beta-ray irradiation of a relatively minute dose.
3. There can be observed rhythmic fluctuations in the composition even of the one and the same fatty acid (e. g. C_18:2) which is specific to each organ.
4. It is difficult to determine the changes in the composition of the long-chain fatty acids induced by ³²P labeled phosphate simply on the basis of gas-chromatographic study conducted at any unit time interval.

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In order to study the effect of X-irradiation on the composition of fatty acids in the body of cancer bearing animals, at first solid Ehrlich carcinoma was transplanted into the right leg of mice and then 500 R/day of X-rays were irradiated on the right leg of the animals consecutively for 10 days (total dosage 5, 000R). The animals were divided into. three groups of the irradiated cancer bearing mice, non-irradiated cancer bearing mice and normal mouse control group. The fatty acid extraction was carried out by the method of Folch et al with (1) tumor and right leg muscle, (2) serum, and (3) liver, of each group, and the determination of the fatty acid composition was made by the gas-liquid chromatography.
1. As the result it was found that the tumor tissue of the irradiated group revealed a greater quantity of linoleic acid than that of the non-irradiated cancer bearing group.
2. The solid Ehrlich carcinoma of the right leg contained a larger amount of stearic acid than that in the right leg muscle of normal mice.
3. As for the composition of total fatty acids in the liver and the serum, the percentage of linoleic acid was found greatest in (1) the control group of normal mice, followed by (2) irradiated tumor bearing mice, and (3) non-irradiated tumor bearing mice in the order mentioned.
4. There seems to be some correlation between the cessation of tumor growth by irradiation and the distribution of linoleic acid.

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With the purpose to study the changes of long-chain fatty acid composition in the serum of the breast cancer patients after radiation therapy, total fatty acids in the serum of the patients with breast cancer, both before and after the radiation teatment, were separated and identified by the the gas-liquid chromatography. The results of the study may briefly be summarized as follows.
1. The total fatty acid composition in the serum at the time when the tumor has grown smaller approaches the level of normal persons in contrast to the level before the radiation therapy.
2. It is considered that the radiation therapy is a success when the polyunsaturated fatty acids, especially linoleic and arachidonic acids are increased and saturated fatty acids are decreased.

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1) Removal of the tymus from guinea pigs within 24 hours after birth causes decrease in number of immunologically competent cells in the tissues, in ability of serum antibody production and in manifestation of delayed hypersensitivity of the skin
2) The thymus cells of guinea pigs are cytomorphollogically divided into large and small lymphocytes, lymphoreticular cells, lyphoblasts and mesenchymal reticulum cells. In addition, there are epithelial reticulum cells, tissue mast cells, neutrohils and plasma cells
3) It is assumed that the lymphoreticular cells are the most possible immunologically competent cells in the thymus. These cells imigrate out of the border portion between the cortex and medulla to the medulla of the thymus through the lymph vessels that lie between the cortex and medulla and settle down in the remote lymphatic tissues. Lymphoreticular cells are also considered as the most imporant immunologically competent cells in these remote lymphatic tissues.

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1) The highest incidence of runt disease is obtained in case of thymus cell transplanted mice among cell graft experiments of various tissues of Db strain mice to R_IIIstrain mice and those of R_IIIstrain mice to Db strain mice.
2) The incidence is found to vary with the age of the donor mice from which thymus cells are supplied. The thymus cell of newborns has no ability to cause runt disease, but the incidence of the disease gradually increase after the age of 2 to 4 weeks of the donor mice.
3) Destruction and loss of lymphocytes are histologically demonstrated in the thymus of the thymus cell transplanted group. The same changes are observed in the spleen of the spleen cell transplanted group.
4) A marked increase of lymphoreticular cells were seen in the course of runt disease.
5) These findings suggest that the thymus of adult mice plays a significant role in immunological response of the body.

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Aanti-tumor activity of OX substance, an unsaturated fatty acid extracted from rabbitliver 24 hours after 3, 000γ irradiation, was studied in lymphatic asites leukemia in methyl cholanthren induced DBA mice.
OX substance was administered intravenoulsy from the tail vein of mice.
Red blood cell and white blood cell count of the peripheral blood, character of ascites and morphalogical changes of ascites cells, pathalogical findings of the visceral organs, body weight and survival period of mice were observed and following results were obtained.
1) Administration of OX substance gave arise prevention of anemia and suppression of development of leukemia in DBA mice with ascites leukemia.
2) OX substance gave no influence to changes of the body weight of DBA mice with acites leukemia.
3) Life span of DBA mice was remarkably prolonged by OX substance administration.
4) OX substance inhibited the infiltration of leukemia cells in the lung, liver, spleen and other organs of DBA mice.
5) OX substznce schowed the strong cytotoxic effect on the ascites leukemia cells in DBA mice.

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Anti-tumor activity of OX substance was studied in the lymphatic ascites leukemia inC BA mice, induved by successive trantation of ascitescell of D BA mice.
Same investigations mentioned in the previous paper were carried out and following conclusions were obtained.
1) Administration of OX substance gave arise prevention of anemia and suppression of develpment of leukemia in DBA mice with ascites leukemia.
2) OX substance gave no influence to changes of the body weiht of DBA mice with ascites leukemia
3) Life span of DBA mica was remarkably prolonged by OX substance administration.
4) OX substance inhibited the infiltration of leukemia cells in the lung, liver, speen and other organs of DBA mice.
5) OX substance schowed the strong cytotoxic effect on the ascites leukemia cells in D BA mice.
6) OX substance gave no influence to the blood picture of the normal rabbit.

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Recently, much interest has arisen in the health administration for middle, small or petty scale industries in our country, though there is the difficulty of approach to thier problems because of economic and social conditions.
Great significance in the study on the enterprises of these scale is in the following points;
(1) the economical role played in our industrial circle,
(2) overwhelming majority both in number of enterpises (99.8%), and in the population of working people there (66.0%),
(3) the necessity of combination of the approaches to the problems in community and industrial health for solving the probloms in the enterprises in these scales, showing quite a clear contrast against lagre enterprises in which the problems could be solved mainly in the enterprises themselves.
At first, the author has discussed the significance of the existence of the middle, small or petty scale industries by analyzing the present-day economical tendency of our country. Then he has chosen an experimental factory of rubber goods manufacture having around 500 workers.
He has managed to set up a dispensary and studied its relationship with the doctors in the environmental community. He has analyzed the clients of various kinds of diseaeses, health counselling and the occupational accidents there, and discussed the situations which have been quite different from those in large enterprises.
Further, he has evaluated the administration done and the changes of the health status of the workers during the research period, using Okayama Medical Index-Health Questionnaire (O.M.I.).
A conclusion was made that the trial practice with scientific analysis described above may be a creative step for the progress to approach the difficult theme in the field of our industrial health.

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In the paper ADL (activity of daily living) was cxamined carefully on those disabled persons registered in Okayama Prefecture, who had discrepancies in length of the lower extremities due to such causes as anterior poliomeylitis, congenital dislocation of the hip joint, fracture and osteomyelitis. In addition, the follow-up studies were conducted on those patients who underwent the operation for the correction of unequal leg length by epiphyseal stapling or lengthening of the lower leg in the Department of Orthopedic Surgery of Okayama University and Kochi and Kagawa. Prefectural Rehabilitation Center for Crippled Children (Kojikaen and Hikarigakuen). From the results of these studies the following conclusions were drawn.
1. In studying the relationship between the unequal leg length and the ADL, not only the length of leg itself causes inconveniences but also original disease or lesion has a great bearing on ADL. Viewing only from the length of leg, it seems that the difference of 2.5-3cm in the leg length is the boundary in adults.
2. On the basis of expected average correction, the equalizing leg length by epiphyseal stapling is an effective and safe method.
3. The lengthening of the lower leg is a reliable method for a wide range of skeletal age provided that the care is taken to prevent complications.

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Malic dehydrogenese (MDH) activities and isozymes of various human organs were measured. The assays of isozyme were carried out by means of agargel electrophoresis. The highest MDH activity was demonstrated in heart muscle. Liver, skeletal muscle, kidney and brain showed considerably high MDH activities. Six fractions were distinguished in many MDH isozymograms. In order of movility towards the cathod, each MDH isozyme was named MD₁, MD₂…MD₆.
Intracellular distribution of each MDH isozyme was investigated by means of cell fractionation, and MD₁MD₅ were confirmed mitochondrial, MD₆ cytoplasmic, in origin.
MDH isozyme-patterns of human organs were divided into 3 groups according to the ratio of mitochondrial MDH (m-MDH) and cytoplasmic MDH (c-MDH).
Group I (m-MDH>c-MDH): heart muscle, kidney, skeletal muscle, white blood cell, red blood cell and lung-tissues.
Group II (m-MDH_??_c-MDH): liver, pancreas.
Group III (This group situates between Group I and Group II): brain, gastric mucosa, and spleen.
Studies on inhibitory effect of p-chlor-mercuri-benzoate (PCMB) on each MDH isozyme and heat stability of each MDH isozyme demonstrated that m-MDH was not inhibited by PCMB and stable to a heat test at 50°C for 30, ' when 1-malate was used as substrate. It was also observed that m-MDH was activated by a high concentration of 1-malate.
According to the standard deviation of MD₆ and MD₃ activites, c-MDH considered regulatory enzyme and m-MDH constitutive enzyme, respectively.

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Malic dehydrogenese (MDH) activities in human serum of various diseases were studied. Elevation of MDH activities were observed in myocardial infarction, acute hepatitis, and some malignant tumors.
Characteristic MDH isozyme patterns were obtained from serum of patients with myocardial infarction and acute hepatitis showing marked elevation of MDH activities.
During the tetrazolium procedure for staining of electrophoreticaly separated serum malic or lactic dehydrogenese isozymes on agargel, without substrate and co-enzyme, two peaks were noticed and named serum “non-specific factor”. These peaks were considered a kind of non specific reactions which resulted from a reduction of the tetrazolium salt electrostaticaly adsorbed on Alb.-α₁, Glb. by SH-groups of these serum proteins.
These reactions were accelerated by the elavation of PH or the temperature, exposure during staining and the prolonged staining time, as well as the rise of concentrations of NTB, PMS and CN- in the staining medium. Considering of optimal conditions of enzyme reaction, the minimum use of NTB, PMS and Na CN, washing stained agargels with PH 4.5 acetic acid Sol., and complete shading during procedure could minimize the influence of this factor.
Two MDH isozymes were demonstrated in agargel isozymograms of rat organs, one migrating towards the cathod and the other toward the anode. The cathodal fraction was considered mitochondrial MDH (m-MDH), and the anodal one cytoplasmic MDH (c-MDH), respectively.
During development, m-MDH showed marked increase in heart muscle. In contrast to this, cMDH of liver and gastric mucosa increased in procedure of development. On the other hand the ratio of m-MDH and c-MDH in kidney remained constant through development.

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A consecutive series of 30 cases of Parkinsonism were examined in this study. A prove with five silver ring electrodes at 5 mm distance from the tip was inserted into the ventrolateral nucleus of the thalamus stereotaxically. Spontaneous thalamic activities of the patients were recorded and analyzed by Walter type analyzer with electrical filters into five bands, i.e. 2-4 c/s, delta band; 4-8 c/s, theta band; 8-13 c/s, alpha band; 13-20 c/s, beta I band; and 20-30 c/s, beta II band. EEG from parieto-occipital region were also recorded and analyzed simultaneously.
Frequency power spectrum of the thalamus showed generally higher theta and delta band activities in both bipolar and monopolar records. In the patients with predominant tremor of the limbs it showed considerable high delta band and marked low alpha band activities, which were clearly differentiated from that of other type of Parkinsonism. This was characteristic in the bipolar record from the thalamus. Duration time of waxing and waning phenomenon of alpha band activity ranged from 0.9 to 2.0 seconds with average 1.2 seconds in the thalamus, but longer duration up to 5 seconds in the scalp lead.
Frequencies of alpha activities were noted mostly from 8.5 to 10.5 c/s. in EEG, but 8.5 to 11.5 c/s. in the thalamic lead. The patients with higher frequencies of alpha activities were closely corresponded to a good candidate for surgery in the thalamic bipolar lead, but not in thalamic monopolar lead or scalp EEG.
On the other hand, a poor candidate for surgery had higher delta and theta activities in the frequency power spectra and slowing of frequencies of alpha activities in the thalamic bipolar lead.
The scalp EEG findings were not specific, but thalamic activities were most closely related to the progress of symptoms, particularly tremor, rigidity and bradykinetic situation of a Parkinsonian patient.

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Electrical low frequency stimulation (1-20 c/s) of ventrolateral (VL) nucleus of the thalamus was performed with a bipolar stimulating electrode of 0.5-1mm distance on 25 cases of Parkinsonism. The evoked potentials were recorded with monopolar and bipolar scalp leads. The records could be averaged directly with ATAC-401 or MC-401 medical data processing computer, which had been used for only monopolar recording. The evoked potentials were noted mostly on the ispilateral side of fronto-parietal region at the regular suprathreshold stimulation, but bilateral evoked potentials with the highest amplitude of the ipsilateral fronto-parietal region at the excessive suprathreshold stimulation.
EEG of fronto-parietal region was analysed before, during and after the VL stimulation by means of Walter-type hand-pass filter apparatus. It was interesting that waxing and waning phenomena were observed in the analysed band, which was concordant with the frequency of stimulation. When 6 c/s stimulation was applied, the phenomena were obtained clearly in the θ band, 10 c/s in the α band. The evoked potentials were assumed as an augmenting response when 5-10 c/s repetitive stimulation was applied to VL nucleus.
The averaged response showed small primary positive-negative-positive phases within 30 msec after stimulation, followed by large late negative phase with 50 to 60 msec of peak latencies. But in some cases, the responses averaged with the computer, showed primary positivephase with 5 to 10 msec and a following large negative phase with 30 to 40 msec of peak latencies, which led into a more variable positive wave with peak latency 50-65 msec. The peak latencies of both positive and negative phases showed a fairly constant duration in the stimulations of lower frequencies (1-10 c/s). The large negativity with peak latency 30-60 msec showed maximum amplitude at 8-10 c/s stimulation. When the stimulations of higher frequencies were appiled, the large negativity became lower and lower in amplitude and finally disappeared at the frequency of 15-20 c/s. It was considered that the large negativity was the most principal component in the augmenting response of VL stimulation.
However, in five cases of parkinsonian patients who showed typical augmenting responses at 5-10 c/s stimulation, recruiting-like responses were also noted at 15-20 c/s. The position of the tip of the stimulating electrode was checked roentgenologically, and identified to be in the regular VL area of the thalamus. It could be considered that ventrolateral nucleus of the human thalamus has some aspect of diffuse projecting systems in it or close relation to them electrophysiologically.

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Japanese neurosurgeons have recently noticed that there are particular Japanese cases whose cardinal symptoms are characterized by motor paresis or apoplectic stroke.
Angiographic findings are most characteristic, demonstrating stenosis or occlusion of the bilateral internal carotid arteries at the site of carotid siphon (C1) and abnormal hemangiomatous vascular network at the base of the brain. 9 cases of the Japanese has been experienced in our clinic.
The author reviewed similar cases from literature and letter inquiry which has been made to all of the neurological clinics in Japan. Then, clinical manifestations of the disease have been elaborated on total 118 cases.
1) Sex and Age: 47 were male and 71 were female. The disease was started from under 15 years or less of age in 77 cases. The cases, which had juvenile onset, showed characteristic clinical features. Therefore, such cases will be referred to as juvenile form and the other adult form.
2) Cardinal symptoms were similar to initial ones. Motor paresis was seen in 59 cases out of 77 cases of juvenile form, while subarachnoid hemorrhage was seen in 20 cases out of 41 cases of adult form as an initial clinical symptom.
3) Prognosis: There has been reported frequent recurrence of the symptoms in period of observation of the patients. The recurred symptom disappeared by itself, so no marked progress was noted in the majority of cases. However, some juvenile cases showed progression of symptoms, and death occured in 4 cases out of 77 cases.
4) Sibling incidence was detected in 8 cases (4 couples) out of all the cases.
5) EEG findings: Background activity of EEG ranged from normal to mild slow wave pattern in resting record. Hyperventilation provoked generalized slow wave easily, which continued persistently after the cessation of it in most of the cases.
6) Sex chromosomes were investigated in two female and one male of authors'own cases but no abnormality was noted.
7) 5 autopsy cases were reviewed. The pathological findings brought no contribution to the pathogensis of the disease.
8) Angiographic examination, which was carried out at different period of time, revealed steady appearance of abnormal vascular network in the majority of case of adult form. The patients of juvenile form, who had progression of their symptoms, showed smaller vascular network at the base of the brain.
9) There has been no report of the case upon the foreign race up to the present time. The reports by W. Weidner and N. E. Leed were on the case of Japanese-American woman, American-born Japanese boy and girl. It is the opinion of the author that this disease would be a particular type of cerebral vascular abnormality of the Japanese and that the etiology of this disease is congenital malformation of cerebrovascular system because of bilateral and symmetrical vascular abnormality, existence of sibling cases and resemblance to embryonal vascular system.
10) It should be stressed for the diagnosis of the disease that serial bilateral carotid and vertebral angiography is absolutely necessary to distinguish it from other occlusive diseases of internal carotid artery.

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There has been reported investigation on 118 cases of this disease in the previous paper, which suggested marked discrepancy of its clinical symptoms between the juvenile form and adult one. Moreover, it has been pointed out that serial bilateral carotid and vertebral angiography should be absolutely necessary to distinguish those cases from other occlusive diseases of the internal carotid, and suggested that this disease would be a particular type of cerebral vascular abnormality of the Japanese. Postmortem examination on five autopsy cases has been done up to the present time, but the pathological findings brought no contribution to the pathogenesis of the disease.
Therefore animal experiment has been attempted to elucidate the pathogenesis of the disease. Complete or incomplete occlusion has been performed bilaterally on the dog brain at the site of carotid siphon (C₁) immediately distal portion to the origin of the posterior communicating artery. The arteries were successfully clipped in 8 dogs. Bilateral carotid angiographies was carried out with the intervals (from 3 months to 12 months) after the surgery on each dogs, but abnormal vascular network was never observed in all cases. The solid molding specimen of the circle of Willis also demonstrated no abnormal vascular network at the site of the occlusion in these experimental dogs. Histological examination revieled a minimal thickning of the wall of the arteries at the distal part of the occlusion and dilatation of artrioles which belong to the middle cerebral arteries. It could be denied by this experiment that the acquired occlusion of the circle of Willis will bring forth the abnormal vascular network at the base of the brain.
The pathogenesis of the disease is still obscure but it is in my opinion that the previous clinical investigation as well as this animal experiment suggested congenital vascular malformation of the circle of Willis.

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The activities of Glucose-6-phosphate dehydrogenase, 6-Phosphogluconate dehydrogenase and Citrate cleavage enzyme, of which increase is known to be associated with an enhanced lipogenesis in experimental animals, were measured in the liver tissues from the patients with liver diseases.
1) The activities of these enzymes were significantly increased in the convalescent stage of acute hepatitis, while no significant changes were found in chronic hepatitis (active or inactive), liver cirrhosis and fatty liver.
2) No apparent correlation was found between the activities of these enzymes and the degree of hepatic fatty infiltration in these liver diseases, suggesting that hepatic lipogenesis might not play a majar role in fatty change of liver encountered in the course of the liver diseases. Alternatively, the increased enzyme activities might reflect some other metabolic alterations associated with hepatic injury.

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The changes of serum NEFA concentration after oral glucose administration were examined in patients with acute hepatitis (convalescent), chronic hepatitis, liver cirrhosis and fatty liver, excluding obesity, manifest arteriosclerotic vascular disorders, diabetes and other endocrine disorders.
1) The fasting NEFA value had the tendency to increase in liver diseases, especially in liver cirrhosis. No correlation was found between the NEFA value and the extent of hepatic fatty infiltration.
2) Although no specific pattern of NEFA response to glucose was found in these liver diseases, the decrease in NEFA concentration following the glucose load became less marked in accordance with the increase in the extent of hepatic fatty infiltration.

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For the purpose to study changes in the metabolism of RES in vivo under anesthesia over a long period a series of experimental observations were conducted with dogs by means of Glycyrrhizin ⁵⁹Fe-colloid method and the following results were obtained.
1. It was found that to the dog under anesthesia the phagocytosis of the RES is clearly inhibited, and with the use of Isozole it is slightly inhibited, while deep anesthesia such as combination anesthesia and low body temperature anesthesia distinctly affects the phagocytic function of the RES.
2. On the other hand, in the study of the hemoglobin synthesis which reflects the metabolic function of the RES, by means of fractionation of hemin iron and non-hemin iron in erythrocytes it was demonstrated that the hemoglobin synthesis is clearly inhibited by anesthesia and deep anesthesia inhibits the synthesis to a greater extent.
3. Simultaneous observations of the total organic iron, hemosiderin, ferritin fractions revealed that under anesthesia the retension of hemosiderin is increased, ferritin is decreased, and the ratio of hemosiderin to ferritin is lessened, suggesting that there develops a retension phenomenon in the RES.
4. The metabolic function of the RES is markedly inhibited by the low body temperature anesthesia at 27°C to 28°C but along with the lapse of time there develops an adaptation-recovery phenomenon and the metabolic function is inhibited more markedly rather than phagocytosis but it does not reach the stage of arresting the reaction.
These findings clearly demonstrate that the Glycyrrhizin ⁵⁹Fe colloid method is a superior one for examining the functions of the RES to the classical method available. Further, in the investigation of the RES by this method it has been suggested that the function of RES is less inhibited by shallow anesthesia while by the deep anesthesia its inhibition is greater, and that under the low body temperature anesthesia more of the primeval function of the RES is maintained, thus rendering many useful criteria of clinical importancs.

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In order to clarify the effects of surgical intervention on the function of the RES, we performed pseudo-surgical intervention on dogs by the Glycyrrhizin ⁵⁹Fe-colloid, and obtained the following results.
1. In the study of the phagocytic function of the RES it was found that simple laparotomy rather accelerates the RES function slightly while in the case of a greater surgical intervention, such as an extensive removal of lymph nodes in the upper abdominal cavity, a marked primary acceleration of the RES function can be observed. In the case of splenectomy performed for the purpose to decrease the quantity of RES tissue, the function is lowered in proportion to the quantity of the tissue removed.
2. As for the hemoglobin synthesis resulting from the iron metabolism of reticuloendothelial cells, a marked acceleration of the function is observed in the case of simple laparotomy, while on the contrary, a strong inhibition is induced by the extensive lymph-node removal of the upper abdominal cavity. In the case of splenectomy such an inhibitory effect on the RES becomes more pronounced when a greater quantity of lymph-node tissue is removed.
3. In the observations conducted on the accumulated total iron and iron fractions in the liver, spleen and bone marrow at 48 houres after anesthesia, it was demonstrated that as the surgical intervention becomes more extensive, there occurs blockade of hemosiderin, and likewise in splnectomy iron accumulation is brought about by the residual spleen but the ratio of hemosiderin to ferritin is reversed, indicating that a strong compensatory function is rendered to the residual spleen.
4. In the study of various functions such as phagocytosis, disposal and synthesis of the entire RES, when the lymph nodes are removed extensively in the upper abdominal cavity, phagocytosis is accelerated only at early stage, but there appears a division of the function as both organic iron and hemoglobin synthesis counteract one another, and in the case of splenectomy the residual spleen exhibits a marked compensatory function, and the compensatory capacity of the liver is also considerable. However, the RES as a whole has been demonstrated to function lesser in proportion to the quantity of the spleen removed.
From these findings it has been elucidated that the removal of the organs from RES affects specifically the functions of each organ, giving valuable criteria for clinical study. Further, it was shown that for the study of RES this Glycyrrhizin ⁵⁹Fe-colloid method is superior to the available classical metdod.

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In an attempt to examine the functions of the RES by assimilate colloids other than iron colloids, linoleic acid-¹⁴C emulsion and lipid emulsion, fatgen, were selected and by treating the RES of the dog with these emulsions observations were carried out on the behaviour of the RES functions at the surgical intervention. The results of the study are briefly presented in this communication.
1. It was fund that linoleic acid ¹⁴C-emulsion is taken up by the RES, is soon saturated, and readily incorporates into fat tissue. For the study of the RES function in animals this is a very usefuly method with a promising future.
2. The lipid emulsion fatgen is taken up and metabolized readily by the RES, proving that the treatment of RES by this emulsion can take place of Congo red method in the clinical examination of the RES.
3. For the examination of the function of the RES of experimental dogs at surgical operation the treatment by the lipid emulsion gives somewhat different results in detail compared with the Glycyrrhizin acid iron colloid, but in the case of splenectomy the compensatory function of the residual spleen is markedly accelerated and the liver in the splenectomized group compensates the removal of spleen, indicating that both methods yield similar results on the whole.
From these findings it seems that the lipid colloid method as well as the Glycyrrhizin iron colloid method are to be highly recommended as the new, excellent methods to be applicable to clinical examinations of the RES functions.

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The author has improved the method of Brom-phenol-blue (BPB) staining on filter paper (original method), and devised the spot method on filter paper pre-stained with BPB (simplified method), and the dipping method of the filter paper pre-stained with BPB (test paper method).
The author has compared the quantities of minute urinary proteins by the original method on one hand, and those by the simplified and the test paper methods on the other.
The quantities of the urinary protein by the simplified method coincide with those by the original method. Also, the quantities of the urinary protein by the test paper method coincide with those by the original method.
The analytical sensitivity of these improved methods was 6 mg/dl of urinary protein. As the improved methods are quite simple and have a quite excellent sensitivity, it is considered to be applicable to the screening of fatigued workers.

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In order to know the relationship between the value of R. M. R. and the quantity of urinary protein, the author measured minute quantities of proteins excreted in the urine under the load of the bicycle ergometer by simplified method as reported in Part 1.
The quantities of urinary protein before and after working in the each shop of a shipbuilding yard, were also measured, and the following results were obtained.
1) Physical exercise was given on a bicycle ergometer and urinary protein was measured. It was observed that the quantities of urinary protein increased in parallel with the value of R. M. R. ranging from 1 to 7.
2) In each shop of the shipbuilding yard, it was also observed that the quantities of urinary protein after working, paralleled with the values of R. M. R.

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The author measured the microquantity of urinary protein after working by simplified method, previously reported in Part 1, and by the test paper method, and also examined it by the above method for the control of fatigued workers and those having of kidney diseases from 10102 workers in total of a shipbuilding yard during 4 years.
The results obtained were as follows.
1) The screening-level of urinary protein excretion after working was estimated to be 0.25‰ from the excretion of urinary protein after 8-hour working on 971 workers.
2) During 4 years, 10102 total workers were checked by 0.25‰ of urinary proteinas to determine screeing-level of fatigued workers and those with kidney disease. As the result it was that 454 were of abnormal proteinuria in the first screening, and 411 of them recovered from abnormal proteinuria controlled by limitation of their overtime work for 1 moth. Using this method, it will be shown that the rate of recovery from the fatigue was 90.5%. Therefore, it seems that the method above mentioned in Part 1, was a useful one for checking temporary fatigue.
In the case of 43 workers, who did not recover from abnormal proteinuria although their overtime work was limited, they were taken as the second cotrol of limitation of overtime work for 1 month as described in the item 2, and for those who did not show any decrease in the protein content they were examined for kidney disease. Of these 43 examined 4 were found to be fatigued, 28 of them with anamnesis of kidney diseases, and 7 of them with severe kidney disease newly found. After successful treatment ot the new patients, they returned to their respective position, while the otheres reurned to their work on the advice of their physician in charge.
It is reasonable to conclude that this microquantitaive determination method is useful for the control of fatigue in workmen as well as for the control of kidney direase.

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