1. PKU患者6名と対照正常人8名にインスリンを投与して,血中フェニールアラニン,チロシンおよびカテコールアミン代謝について検討した.
2. インスリン投与によってPKU患者の血中フェニールアラニン値は症例毎に著しい変動を示し,血中フェニールアラニン値の低下する例が認められる反面,増加する例も認められた.
3. PKU患者にインスリンを投与すると,血中カテコールアミン値に増加傾向が認められた.チラミン,オクトパミンは60分後に著明な増加を示す例が多くみられた.
4. PKU患者のうち,インスリン投与によって,フェニールアラニン代謝およびカテコールアミン代謝の改善が認められた症例については,今後適当な方法を開発することにより,治療効果が期待される.

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1. 対照正常人6例とPKU患者6例について,インスリン投与前と投与120分後の血中遊離アミノ酸の変化を検討した.
2. 対照正常人では, Aspが2例で増加したほかはすべてのアミノ酸が減少し, Met, Leu, Arg, Ileの順に減少率が大であった.
3. PKU患者では, Pheは4例, Tyrは全例で減少した.
4. PKU患者でGlu, Asp, Arg, His, Tau, Trp, Orn, Proの増加例があった.

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With liver biopsy materials obtained from 28 cases out of the 54 patients receiving pulmonectomy and being given blood transfusions after chemotherapeutic treatment for pulmonary tuberculosis, functional and histological studies of the liver were carried out with lapse of time, and the results are summarized briefly as follows.
For those cases showing the GPT, GOT, and BSP level over 100 gamma/ml (89 Karmen units), 60 gamma/ml (83 Karmen units), and 10% respectively, it is consistent with diagnosing them clinically as the cases of post-transfusion hepatitis in view of their histological findings of the liver. If judged under the above-denoted criteria for diagnosis, three out of six nonicteric cases were not to be recognized as hepatitis. Of three parameters - the serum GPT and GOT levels and BSP clearance, even one of these set below the level above-indicated, was not to be available because of the increasing possibility to result in an erroneous diagnosis. The GPT level of 100 gamma/ml serves well as a screening test of post-transfusion hepatitis, but there is a pitfall of erroneous over-diagnosis in the period of less than one postoperative month. The GOT level of 60 gamma/ml is higher than the standard one so that it is possible for the cases of mild non-icteric hepatitis often being missed. Since the judgement depending only on the criteria of the BSP level is possibly prone to cause us either to overdiagnosis, or to under-diagnosis the hepatitis lesion, it is desirable to refer simultaneously to the GPT and GOT levels. In the diabetics the serum GPT, GOT and BSP are all apt to rise to abnormally higher levels than to be expected from the biopsy findings.
Within one post-operative month the functional test values of the liver occasionally showed an abnormal rise, due possibly to an operative injury. In addition a transient, post-operative rise in the levels of these transaminases proved to be attributed to same infective complication of operation.
The incubation period of the disease we studied, ranged from six to twenty weeks - most frequently in the period between six and ten weeks. The incidence of the disease was 51.3% and 53.5% on the bases of biopsy findings and clinical illness respectively, and appeared to be higher than formerly described. Of the cases we studied sequentially there were some cases where the disease had progressed in a short course of their illness to evolve into chronic hepatitis, or even to cirrhosis.

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With 54 cases receiving pulmonectomy as the subjects of study, observations were carried out over the period of 120 days after blood transfusion with lapse of time, for the purpose to determine the liver functions in those patients by means of Paul-Bunnell test, cold hemagglutination, chick cell hemagglutination, monkey cell (Macaca rhesus erythrocytes) hemagglutination, and the correlation between the each hemagglutination reaction and the serum transaminase level was studied. The results are briefly summarized as follows.
The transient rise of cold hemagglutination titer and the elevation of serum transaminase level occured concomitantly especially in the incubation period. After the onset of the desease, the rise of cold hemagglutination titer was also observed in relation to the elevation of serum transaminase level. However, the rise of cold hemagglutination titer here which is due probably to viremia was less than that in the incubation period.
Paul-Bunnell reaction revealed no remarkable difference between the titers in the incubation period and after the onset.
Either chick cell hemagglutination reaction or monkey cell (Macaca rhesus erythrocytes) hemagglutination reaction showed no remarkable elevation in relation to serum transaminase.

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The tumor, induced by intramuscular inoculation of methylcholanthrene in the thigh of mice, was removed by amputation of the leg and the cell was isolated by mincing and trypsinizing the tumor fragment, and suspended in isotonic saline in counted number after viability was tested by trypan blue dye stayning. Mitomycin C (MMC) and Urokinase (UK) was administered either in vitro or in vivo and an effect was evaluated in the transplantability of the tumor cell which was inoculated in the subcutaneous tissue of the back of their own hosts. The results were summarized as follows:
1) Only when the tumor cell was inoculated with MMC, the concentration of which was minimally enough to lower the transplantability by itself, the addition of UK suppressed the take of the tumor, slightly more than that in MMC treatment. No evidence was obtained that the concentration of MMC below the above gained cytostatic effect by the addition of UK in vitro.
2) Definite suppression of take of the transplanted tumor cell and marked prolongation of interval between the transplantation and take were observed, when the combined intraperitoneal administration of MMC and UK was started in the day of the transplantation, compaired with that in mice MMC alone was samely given. The growth of the tumor was retarded in accordance with this suppression in the tumor take. It was also observed that the take of the tumor cell was diminished to some extent even in mice treated with UK alone.
However, when the treatment was started 10 days after the transplantation, the growth of established tumors was not affected by the combined application of UK.
It was concluded that adjuvant effect of UK in anticancer chemotherapy for prevention of tumor metastasis could be expected and an assumption was made that the mechanism lie in interruption of tumor cell lodgement through fibrinolysis caused by UK administration.

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The term of “follicular hapatitis” has been proposed to certain cases of chronic active hepatitis with an intense lymphoid cell accumulation forming a follicular appearance in the portal triads.
In this study, the ultrastructural analysis of the lymphoid cells forming a follicular accumulation in the portal tracts, and of a relationship between the mesenchymal cells and hepatocytes at the destructed limiting plate was attempted. Ultrathin sections of the liver biopsy specimens obtained from a patient with follicular hepatitis were cut immediately adjacent to a semithin section which was stained with toluidin blue and in which the follicular accumulation of lymphoid cells and a destructed limiting plate were observed through a light microscope.
The center of the follicules consisted of immunoblasts and reticulum cells of both the nonphagocytic branching and phagocytic varieties. Lymphoblasts, immature and numerous mature lymphocytes, plasma cells and a small number of macrophages were observed surrounding the center. The mitotic figure of these mesenchymal cells was found to be on the increase.
Macrophages were also found in the area where the liver cells and the portal tracts adjoined. No hepatocellular degeneration was observed at the sharp border between parenchyma and portal tracts. In the area showing the destructed limiting plate, lymphocytes and, occasionally, plasma cells were adjacent to hepatocytes and/or ductular cells. These mesenchymal cells, especially the lymphocytes, indented the hepatocytes and, sometimes, their plasma menbranes were coapted. The hepatocytes lacked microvilli at the area of coaptation, and the degeneration of their cell organelles that was a marked vesiculation and vacuolization of endoplasmic reticulum accompanying a loss of ribosomes, was observed near the coaptation. In the ductular cells coapted with lymphocytes, similar degeneration of the cell organelles was observed and basement membranes disappeared.
These results revealed that in these follicules in protal triads mesencymal cells actively responded to antigen stimulation and that a cellular immunity might also be involved in the pathogenesis of chronic active hepatitis.

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I. Protruded type gastric diseases
In applying β-Glucuronidase (β-Glu.) staining to the biopsied gastric mucosa so that the enzyme's physical and chemical properties were fully utilized. Attempts were made to determined an optimal condition. Patients those whose basal gastric juice PH 3.0 or higher level were selected and β-Glu. activity of the gastric juice was measured. The results are summarrized as follows: 1) With atrophic hyperplastic gastritis, there were cases whose tegmental epithelium showed a rise in β-Glu. and their gastric juice β-Glu. activity was also slightly high. 2) With gastric polyps, there was a trend for strong β-Glu. activity at the tegmental epithelium showing a hyperplastic change, The gastric juice β-Glu. activity was also slightly elevated. 3) With early cancer types I and IIa, I found a marked rise in the β-Glu. activity as compared with benign cases. 4) With metaplastic gastritis, the goblet cells were unaffected by β-Glu. coloring and the β-Glu. activity tended to be low.
From these findings, it is concluded that in benign cases gastric juice β-Glu. activity rises if mucosa β-Glu. activity have been elevated. Especially with cases whose tegmental epithelium β-Glu. activity has risen, gastric juice's β-Glu. activity tended to become high.
II. Concaved type gastric Diseases
Stomach ulcer, early cancer IIc, advanced cancer Borrmann II, III and IV, were tested by applying -Glu. histochemistry to the biopsy of stomach mucousa. Cases in which basal gastric juice PH 3.0 or higher level were selected and measurement was made on β-Glu. activity of biopsied gastric mucosa and gastric juice. With respect to β-Glu., early stomach cancer types I, IIa, and IIc were compared. Also, early comparison was made between progressive cancers.
The results are summarized as follows: 1) With stomach ulcer, the β-Glu. activity in both biopsy of the gastric mucosa and gastric juice was low during the active stage. On entering the healing stage, a rise of β-Glu. was seen in regenerating epithelium. 2) In all the well-differentiated adenocarcinomas of early cancer type IIc, Borrmann II, III and IV types, mucosal β-Glu. activity was similarly elevated but gastric juice β-Glu. activity remarkably rose with the latter. 3) Comparing early cancer types I and IIa with early cancer type IIc, in the case of well differentiated adenocarcinoma the mucousal membrane β-Glu. activity was about the same, but the gastric juice β-Glu. activity showed a higher value with type IIc, which is a concaved type. 4) In all the poorly differentiated adenocarcinoma, β-Glu. activity was highest in the interstitial tissue and in all the well-differentiated adenocarcinoma, β-Glu. activity was highest in the atypical glands.

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The blood galactose concentration was assayed by a galactose oxidase method and intravenous galactose test was performed for liver disease patients.
1. Immediate deproteinazation was necessary after the blood sample was drawn because of rapid decrease of galactose concentration in the whole blood. The color development after the addition of galactose oxidase in the developing system took 3 to 4 hours when the concentration of galactose was 10 mg/dl or less.
2. A standard curve was straight when the concentration was 60 mg/dl or less. But another standard curve was necessary when the concentration was 2 to 3 mg/dl.
3. A blood galactose concentration was about 0.5 mg/dl befor the galactose infusion.
4. A galactose tolerance test was performed by measuring blood galactose every 15 min. for four times after the infusion of 175 mg/Kg body weight. A galactose disappearance curve showed straight line in 72 out of 74 cases except 2 cases, in which cases galactose T_1/2 could not be determined.
5. The mean value of galactose T_1/2 in 10 normal cases was 10.5±1.9 min. and normal upper limit was determined to be 14 min. (mean +2 S. D.).
6. The galactose T_1/2 correlated well with concentrations at 45 min. and 60 min. which could be markers of a galactose tolerance test.
7. No side effect was noticed in the performance of the galactose tolerance test.

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An intravenous galactose tolerance test with single injection of galactose of 175 mg/Kg body weight were performed in the patients with various liver diseases who admitted to The Okayama University Hospital, and half time of galactose disappearance (Gal T_1/2) was obtained.
1. The normal value of Gal T_1/2 was 10.5±1.9 min. and Gal T_1/2 values in the patients with acute hepatitis in icteric stage and in convalescent stage were 14.2±6.9 and 11.3±1.3 min. In the patients with chronic hepatitis and precirrhosis, Gal T_1/2 were 11.4±1.5 and 13.3±1.9 min., respectively. Gal T_1/2 values in cirrhotic patients were remarkably elevated up to 22.3±7.1 min. In patients with extrahepatic obstructive jaundice, Gal T_1/2 values were 12.4±2.4 min. and patients with intrahepatic cholestasis and fatty liver had normal Gal T_1/2 values.
However, 2 out of 5 patients of extrahepatic obstructive jaundice showed elevated value of Gal T_1/2, in which cases secondary biliary cirrhosis was revealed at autopsy.
2. Gal T_1/2 values were closely correlated with K_ICG values and Gal T_1/2/ICG T_1/2 value was appeared to be a marker for the differential diagnosis of parenchymal and obstructive jaundice.
3. Gal T_1/2 values were correlated well with K_ICG, BSP, serum albumin, serum gamma globulin, A/G ratio, ZST and blood NH₃ levels, but were not correlated with total serum bilirubin levels, ALP and S-GOT activities.
4. Histological examination showed that the elevation of Gal T_1/2 values were closely correlated with the development of fibrosis, disarrangement of hepatic lobules and hepatic cell necrosis.
5. The peritoneoscopic observation indicated that the Gal T_1/2 value appeared to increase in parallel with completion of the nodular formation on the liver surface.

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Heterogeneous groups of hepatocytes with different staining characteristics to eosin are found in patients with various chronic liver diseases. These staining characteristics seem to have some relationship to the progression of chronic liver diseases. To examine this relationship, biopsy specimen from 184 liver disease cases, were examined by routine methods, histochemical methods for enzyme quantitaion. RNA staining and immunohistochemical, identification of albumin. The results were as follows.
1) Eosin-intense hepatocytes occupying part of the liver lobule or forming a whole nodule had a high incidence of binucleated cells; normal or elevated levels of glucose 6-phosphatase, succinate dehydrogenase and glutamic-oxaloacetic transaminase; increased nucleolar and cytoplasmic RNA; many albumin containing hepatocytes; and normal glucose 6-phosphate dehydrogenase activity. These eosin-intense hepatocytes seemed to be normal except for the intense staining of eosin and these hepatocytes were probably at the stage of regeneration. Pale hepatocytes with a weak affinity for eosin showed reduced function and to be dedifferentiated. Nodules containing these plale hepatocytes were more expansive.
2) Hepatocytes with different staining characteristics for eosin were found only in patients with chronic hepatitis with sublobular necrosis and liver cirrhosis. The eosin stained group was most frequently observed in the early stage of liver cirrhosis and disappered at late stages. Eosin staining was weak in hepatocytes with progressively increased, well developed cirrhosis with expansive regenerating nodules.
3) Correlations were present in a large number of cases between the size of the hepatic necrosis and the incidence of eosin-intense hepatocytes. This relationship was most prominent at the stage of resorbtion after hepatic necrosis.
4) In at least some specimens, eosin-intense hepatocytes were found around the portal vein. An adequate blood supply may thus be important factor for eosin intense staining.

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It has become evident from reports by neurosurgeons, neuroradiologists and pediatricians that the syndromes of transient hemiplegia or convulsions in children (under 16 years of age) and subarachnoid hemorrhage or hemiplegia in adults occur with a particularly high frequency in Japan. Angiographic findings in these patients revealed marked stenosis or obstruction at the terminal portion of bilateral internal carotid artery (most of the cases showed C₁ obstruction) and bilateral arterial vascular networks at the base of the brain. The syndrome was given the name “cerebral basal rete mirabile” by the Japanese and is also variously called moyamoya disease or cerebral arterial rete.
Our clinic has experienced thirty-three cases of this disease during the past 12 years (19631974). Thirty of these cases (18 adults: 11 males, 7 females and 12 children: 4 males, 8 females) are presented with discussions of the symptoms, clinical course and angiographic findings. Bilateral carotid angiograms were performed in each case. In one particular juvenile case, angiography performed on three different occasions revealed marked changes and these six films are presented for discussion. In sum total, therefore, 36 carotid angiograms from 18 adult cases and 28 from 12 juvenile cases have been discussed.
Each angiogram was discussed in terms of grade of narrowing throughout the internal carotid artery, filling of the ophthalmic and posterior communicating arteries, development of the cerebral basal rete mirabile, visualization of the anterior, middle and posterior cerebral arterial regions and development of the leptomeningeal anastomoses. Narrowing was classified into three groups: none, moderate and marked. Filling of the ophthalmic artery and its branches was classified as mild (+), moderate (++) or marked (+++), as was filling in the posterior communicating artery. Development of the cerebral basal rete mirabile and visualization of the anterior, middle and posterior cerebral arterial regions were both reported as good (+++), fair (++) or poor (+).
1) Moderate or marked narrowing throughout the internal carotid arteries was observed in 40% of adult angiograms and 45% of juvenile angiograms.
2) In 9 cases out of 18 adult cases and 9 cases out of 12 juvenile cases, bilateral internal carotid arteries showed almost equal size throughout.
3) The time intervals from the onset of symptoms to angiography examinations showed no statistical correltion to the grade of narrowing of the internal carotid arteries.
4) The collateral circulation to the frontal lobe or frontal base via the medical frontal artery, supra-orbital artery or anterior and posterior ethomoidal artery originating from the ophthalmic artery were detected in 34 out of 64 carotid angiograms (53%).
5) The posterior communicating artery was visible in 53% of adult carotid angiograms and 61% of juvenile carotid angiograms.
6) Leptomeningeal anastomoses were often observed. The most frequently detected leptomeningeal anastomosis originated from the posterior cerebral artery to the middle cerebral artery. The second most frequently detected anastomosis was from the posterior cerebral artery to the anterior cerebral artery. These leptomeningeal anastomoses were detected in the distal regions of the R. splenii, posterior temporal and parietooccipital arteries. Anastomosis from the middle cerebral artery to the posterior cerebral artery was seldom visible.
7) Well developed cerebral basal rete mirabile were more often detected in children, while the poorly developed predominated in adults.
8) 80% of the cases showed almost symmetrical development of cerebral basal rete mirabile. The branching of small vessels forming the cerebral basal rete mirabile or obstruction level of the internal carotid artery was not always symmetrical.
This author developed the “visualization index” of internal carotid angiograms.

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Histochemical studies have been carried out to evaluate the effect of evacuation of hematoma in the case of the hypertensive intracerebral hemorrhage and also the effect of oral administration of pyridinol-carbamate in such surgical procedure.
Experimental renal hypertension of 34 male rabbits was made by Goldblatt's method, 12 rabbits were dead for hypertensive condition, including a rabbit with massive intracerebral hemorrhage.
Normal 4 rabbits were used as control group.
Artificial intracerebral hematoma was made in 18 hypertensive rabbits by injection of 0.3 ml of venous auto-blood into the area of the internal capsule through a small burr hole stereotaxically.
The hematoma were evacuated by insertion of 18 gauge needle 3 days after the blood injection.
The results were as follows:
a) Rabbits of experimental hypertensive intracerebral hematoma were divided into two groups; 5 rabbits medicated with pyridinol-carbamate of 30 mg/kg B. W. for about 9 weeks preoperatively and 4 non-medicated rabbits.
In the non-medicated group, enzymatic activities of LDH of Embden-Meyerhof pathway, SDH and MDH of TCA cycle, Cy-O of the electron transport system and also Al-p, Ac-p of the hydrolytic enzymes were diminished in the adjacent area of the hematoma. This indicated the considerable decrement for maintenance of metabolism, tissue respiration and the cell function in that area. In contrast, G-6-PDH of Warburg-Dickens pathway was accelerated in the cortex. It suggested that hexose-monophosphate shunt was playing an important role of metabolism in this pathological conditions.
These enzymatic activities of medicated group showed also similar pattern to that of nonmedicated group. They showed, however, rather minimum changes.
b) In 9 rabbits with hypertensive intracerebral hematoma, the hematoma were evacuated afterwards. These rabbits were also divided into two groups; 5 medicated with pyridinolcarbamate and 4 non-medicated rabbits.
In the non-medicated group, LDH, SDH, MDH activities as well as Ac-p and Al-p activities were decreased in the adjacent cerebral tissue of the evacuated hematoma. However, Cy-O activity showed almost normal. This indicated that extirpation of the blood-clot was effective for the restoration of the destructed blood brain barrier and the disturbed metabolism in the cerebral tissue.
In the medicated group, these all enzymatic activities showed almost normal in that area.
These results suggest for us that the surgical evacuation of intracerebral hematoma is a choice of treatment and that the preventive medical treatment such as oral administration of pyridinol-carbamate should be combined with the surgical management under these hypertensive condition.

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I discussed on the lymphnode metastasis and prognosis of 134 cases of breast cancer patients from the stand points of hormonal circumstances in this paper. 17-Ketosteroids and 17-hydroxycorticosteroids were checked as urinary steroids. α-and β-globulins were considered as steroid binding substance groups. These factors analyzed comparing with lymphnode metastasis and prognosis of patients with breast cancer. The favorable hormonal circumstances were as follows; 17-KS≥3mg, 17-OHCS≥2mg/day, α-gl.<13%, and β-gl.>11%. Patients in favorable circumstances have good prognosis, and react for therapies even in advanced and recurrent cases. The poor hormonal circumstances for breast cancer patients were as follows; 17-KS<3mg, 17-OHCS<2mg/day, α-gl.≥13%, and β-gl.≥11%. The patients in poor circumstances have poor prognosis, and not react for therapies in advanced and recurrent cases.

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Serum estradiol were examined by radioimmunoassay in 80 patients with breast disease; 13 normal controls, 18 mastopathies, 33 breast cancers, 7 oophorectomized, and 9 adrenalectomized. Estradiol extraction method was modified by urea combing, and obtained accurate results by removing of lipids substance disturbing of radioimmunoassay. Premenopausal mastopathies have a relative high values than that of normals, but within normal limits. Postmenopausals have lower values than that of premenopausals. Breast cancers have various values most of within normal limits. Postmenopausal breast cancers also showed similar results, but more various than that of premenopausals. The patients after hormonal surgery have low values. Hormone therapy for advanced and recurrent breast cancer is selected by hormone Hependency of tumor, but the success chance is more expectably by agreement with hormone concentration in serum. Estradiol assay is useful as an indicator for surgical hormone therapy.

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