Effect of antianginal drugs on the regional blood flow in the ischemic myocardium and systemic hemodynamics induced with coronary constriction was studied using twenty eight anesthetized open-chest dogs. The regional myocardial blood flow in the inner- (subendocardial) and outer- (subepicardial) layer of the left ventricular wall was continuously monitored by heated cross-thermocouples designed according to Grayson's heat exchange principle. The left circumflex branch of the coronary artery was gradually constricted by a screw type constrictor until myocardial reactive hyperemia following 15-second occlusion of the vessel nearly disappeared. Subsequently, the antianginal drug (nitroglycerin, 20μg/Kg; dipyridamole, 0.3mg/Kg, or prenylamine, 1.0mg/Kg) was administered intravenously.
The results were as follows:
(1) Almost no difference in the regional blood flow between the inner- and outer-layer was present before coronary constriction. After coronary constriction, the flow through the inner-layer and the flow ratio of the inner- to the outer-layer (I/O ratio) in the ischemic myocardium decreased and left ventricular end-diastolic pressure (LVEDP) was slightly elevated.
(2) Nitroglycerin produced essentially no change in the flow through the inner-layer despite a concomitant drop in aortic blood pressure after an initial decrease, whereas it did a remarkable decrease in the flow through the outer-layer. Therefore, the I/O ratio in the ischemic myocardium was elevated significantly from 1 to 7.5 minutes after the administration. During this period aortic blood pressure gradually returned to the previous level and LVEDP was still lowered.
(3) Dipyridamole produced a decrease in the flow through the inner-layer, while only minimal change was observed in the flow through the outer-layer. Consequently, the ratio in the ischemic myocardium was reduced significantly from 1 to 5 minutes after the injection when aortic blood pressure was lowered and LVEDP remained unchanged.
(4) Prenylamine caused a more decreased flow through the inner-layer than the outerlayer. Hence, the ratio in the ischemic myocardium was reduced from 1 to 3 minutes after the injection when aortic blood pressure was lowered and LVEDP remained unchanged.
As mentioned above, the non-uniform distribution of blood flow in the ischemic myocardium following coronary constriction was improved by nitroglycerin and further augmented by dipyridamole or prenylamine. The different effects of these antianginal drugs on the regional myocardial blood flow and its distribution in the ischemic myocadium might suggest that these drugs have different sites of the action on the coronary vascular bed and effects on the systemic hemodynamics, especially on the left ventricular preload.

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Since 1970, we have been trying to culture cells of human hepatoma, hepatoblastoma and human embryonic liver for the purpose of researching the nature of human liver cells and related diseases. In our laboratory we succeeded in establish 2 cell lines from hepatoma (HLE and HLF) in 1975 and a cell line from human hepatoblastoma (HUH-6) in 1976. Then we tried to culture from human embryonic liver. We could not establish an epithelial cell line from human embryonic liver, but could obtain three epithelioid cell lines and got some important results. The results are summarized as follows.
1. The most important condition to maintain the epithelial cell of liver alive in vitro is the age of embryo and freshness of it: the older the embryo, the better condition we got, and the fresher, the better.
2. We have tried many growth media to find the selective growth of liver epithelial cell in vitro and succeeded in obtaining media suitable, not completely but satisfactory, for maintenance of epithelial cells. The media we got were LD + Glutamine and RPMI 1640 + Lactalbumin.
3. Bovine serum is suitable for the maintenance of liver epithelial cell and human serum showed marked cytotoxic effect on cell growth.
4. Inoculum cell number of living large granular hepatocytes from 2 to 10×10⁴/ml showed good maintenance of epithelial cells in vitro for 60 days.
5. We could recognize 5 kinds of cells under phase contrast microscope and cover-slip examination.
i. Large granular hepatocytes (mature type of liver epithelial cell).
ii. Small agranular epithelial cells (immature type of liver epithelial cell).
iii. Fibroblasts.
iv. Endothelial epithelium (Kupffer's cell).
v. Hematopoietic cells due to extramedullary hematopoesis.
6. Marked proliferation of mesenchymal cells were observed.

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Two patients with K-type IgG myeloma are reported. These patients were admitted to the Mitoyo General Hospital and studied for long periods.
Case 1: 56 year-old woman, had typical bony lesions and atypical plasma cell proliferation in the bone marrow. Bence-Jones protein in her urine was negative. The serum IgG level was 4.38g/dl. She survived for 29 months after the diagnosis.
Case 2: 85 year-old man, survived for 41 months after the diagnosis was established. There was no bony lesion in X-Ray examination. Uninary Bence-Jones protein was negative. 16.6% of atypical plasma cells were found in the bone marrow. Serum IgG level was 3.3g/dl.

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Total parenteral nutrition (TPN) has induced a new complication of hypophosphatemia. This study was to real phosphate metabolism by determing nitrogen balance, phosphate balance and serum inorganic phosphate level in rabbits that had been maintained on TPN for 2 weeks.
Results obtained are as follows.
1) It was necessary to supply 10-15 mEq/100 Cal of phosphate to maintain serum phosphate level within normal range.
2) Phosphate balance was negative even if phophate of 15 mEq/100 Cal was given when daily intake calories was subnormal. Therefore, to obtain positive balances of phosphate and nitrogen, fairly large supply of calories (about 93 Cal/kg/day) and phosphate (about 10 mEq/kg/day) was necessary.
3) To evaluate phosphate metabolism, it was necessary to be aware of phosphate balance, but also serum phosphate and 2, 3-DPG in erythrocyte.
4) It was also found that phosphate balance in TPN was under control by calorie intake and phosphate supply.

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The left middle cerebral artery (MCA) was occluded at its origin via a subtemporal approach under operating microscopic control in 24 dogs.
In 8 of these 24 dogs, end-to-side anastomosis between the maxillary artery (MA) and a branch of the left middle cerebral artery (MA·MCA anastomosis) was completed 4 hours after MCA occlusion (prompt bypass). In 5 dogs, MA·MCA anastomosis was performed 3 weeks after MCA occlusion (delayed bypass). These MA·MCA anastomoses were carried out with microsurgical technique as well. Remaining 11 dogs without MA·MCA anastomosis were used for control animals.
Each animal was observed clinically every day until sacrifice.
In control animals, common carotid angiography was performed just prior to sacrifice between 2nd and 5th postoperative weeks. Treated animals were studied with selective external carotid angiography 2 weeks after MA·MCA anastomosis.
After sacrifice, transcarotid perfusion with 10% formalin solution was carried out, the brains were removed carefully, and they were additionally fixed in 10% formalin for 2 weeks. Each brain was sectioned, stained and examined histologically.
1. MA·MCA anastomosis was devised as a new experimental model for extracranial-intracranial bypass graft in the dog. In prompt bypass of 8 dogs, 7 cases showed patency of anastomosis (88%), and in delayed bypass of 5 dogs, angiogram revealed 4 patent anastomosis (80%). In successful cases, angiogram demonstrated excellent filling of the entire territory of MCA through the new shunts.
Anatomical and spatial advantage of the MA seemed to have brought good results in our series of anastomosis than that of other previous experimental extracranial-intracranial bypass graft in the dog. This is the first report on successful patent bypass graft after long-term occlusion of the MCA in animals. It seems that this new experimental model brings the progress in the field of studies of extracranial-intracranial bypass graft for cerebral infarction.
2. Clinical evaluation of all control animals showed mild to severe neurological deficits, mainly contralateral hemiparesis, or death. On the other hand, animals with patent prompt bypass demonstrated no neurological deficits.
Gross and histological evaluation of the brains showed that permanent occlusion of the MCA produced medium or large-sized infarct located in its territory in control animals, and patent prompt bypass usualy caused no or only microscopical infarct. In patent delayed bypass, the size of infarct seems to be smaller than that of non-treated animals.
No hemorrhagic infarct caused by revascularization was found in treated animals with both prompt and delayed bypass grafts.
There was fairly good relation between the neurological deficits and the pathological features in the brains.
In general, it seemed that animals with patent bypass grafts fared better than untreated animals both clinically and pathologically.
This experimental data suggest that reestablishment of blood flow by extracranial-intracranial bypass graft, especially in prompt bypass, might lead to significant restoration of neurological function without pathological damage of the brain.

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Lysosomal enzymes were examined in synovial fluid, synovium, synovial fluid leukocytes and peripheral blood leukocytes of 40 rheumatoid arthritis (RA) patients and in synovial fluid and synovium of 19 osteoarthritis (OA) patients. Complement level and anticomplementary activity were examined in 13 RA synovial fluid.
The results are summarized as follows: 1, In the supernatant synovial fluid and the synovium of RA patients, cathepsin D (C-D) and β-glucuronidase (β-G) activities were higher than those of OA patients. A positive correlation was present between the synovial fluid leukocyte count and C-D activity and between synovial fluid leukocyte count and β-G activity. RA synovial localization of β-G activity was demonstrated by light microscopy. The synovial lining cell of RA patients showed the strongest β-G localization.
2, No significant differences were found in C-D and β-G activities between RA synovial fluid leukocytes, RA peripheral blood leukocytes and normal human peripheral blood leukocytes. These results suggested that there were little differences in the inflammatory leukocytes and the noninflamatory leukocytes.
3, C-D and β-G activities in the supernatant synovial fluid and synovial fluid leukocytes were higher in RA patients with positive RF in synovial fluid than negative RF in synovial fluid. The results of this study suggested that the RF was displaced to the inflamation RA joint.
4, The presence of low complement levels and anticomplementary activity in RA synovial fluid suggested the role of the immune complex in the RA synovial cavity.
5, These results suggest that the high level of lysosomal enzymes in RA synovial fluid was due chiefly to the synovial membrane.

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Urokinase was administered to knee joint effusions of rheumatoid arthritis (RA) patients who showed no effects to various other RA treatment methods. The fibrinolytic system and the lysosomal enzyme activities of the synovial fluid of 19 RA patients and 10 osteoarthritis (OA) patients were examined before and after treated with urokinase, and the clinical effects of urokinase treatment were examined.
1, Plasmin activities were not present in the synovial fluid of RA patients, but streptokinase activating plasmin (SK-pl.) and euglobulin streptokinase activating plasmin (eug.-SK-pl.) activities were present. Fibrin degradation product (FDP) levels were higher in synovial fluid of RA patients than OA patients.
2, Urokinase was injected into the synovial cavity and at 24 hours after injection, the synovial fluid was collected and the fibrinolytic system was examined. Plasmin activity was not present. Under urokinase treatment, SK-pl. activity was not altered, and in some cases the eug. -SK-pl. activities were elevated compared to untreated synovial fluid. FDP was elevated and activated the fibrinolytic activity.
3, After treatment with urokinase, synovial fluid showed a arise in cathepsin D and β-glucuronidase activities and in synovial cell count. This shows that the synovial inflamation was increased temporarrly by urokinase treatment.
4, Urokinase treatment was not effected in RA cases that showed a low plasminogen and a high plasmin inhibitor in synovial fluid. Joint effusion was not decrease after urokinase treatment in RA cases that showed elevation of plasmin inhibitor and no elevation of FDP levels.
5, Urokinase treatment was effective in about 80% of cases for decreasing RA joint effusion. Urokinase administration resulting in the dissolving of fibrin in RA synovial fluid is a useful treatment.

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In relation to etiology, pathophysiology and therapy of surgical diseases, influence of estrogen has aroused various discussions and its assay has become quite necessary. However, the methods of measuring urinary estrogen such as those of Brown, Bauld, Cohen or radioimmunoassay available at present have some disadvantages in which procedures are complicated and take quite some time until the results can be obtained and special apparatuses are required. For these reason, I have devised a simple method of applying E₃-Kit method to measure estrogen of a high concentration in pregnant women to measure urinary estrogen of non-pregnant women as well as that of men.
With 9-hours night urine as the material, estrogen is allowed to be absorbed by a 50ml of Amberlite XAD-2, and this is then extracted with methanol, and the condensation of the extract was accomplished by evaporation of the methanol. Then the colorimetric quantitation is done by E₃-Kit method. By this method it is possible to measure over 5μg/9hrs. of estrogen.
In calculating the dose response curve by this method, the coefficient of correlation was as high as 0.998, although the recovery rate was 43.5%. Furthermore, as the quantity of estrogen excreted in the night urine was found to be in a direct proportion to that excreted in the day urine, the multiple of 24/9 was made to represent the quantity of estrogen excreted in one-day urine. The same urine sample was then assayed by this method as well as by Brown's fluorescent method, and the coefficient of correlation was calculated. Such tests showed that the coefficient was 0.763. These results indicate that this assay method can be sufficiently applicable to the clinical practice.
The quantity of estrogen excreted in the urine was measured by this method in the cases with various diseases having the sex limit. The urinary estrogen level in the menstruants with aortitis syndrome was distinctly lower than in the control menstruants group, but in the cases of aortitis syndrome after menopause it did not show any outstanding differences. The estrogen level in the cases of arteriosclerosis obliterans and Buerger's disease of males tended to be somewhat higher than normal males.

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Clinicopathological studies of the histogenesis of the thyroid cancer on the emphasis of morphological features and growth pattern of the occult thyroid carcinoma measuring under 1.0 cm in diameter obtained at autopsy and surgery were performed.
The occult thyroid carcinoma observed from the routine section of the thyroid gland obtained from 500 cases at autopsy and 259 cases at surgery were 21 cases (4.2%) and 10 cases (3.9%), respectively. Histological typing were 25 cases of papillary adenocarcinoma and 6 cases of follicular adenocarcinoma.
Papillary adenocarcinoma cases were subdivided histologically into sclerosing, cystic and non-sclerosing types. The sclerosing type showed the proliferation of the fibrous connective tissue in the tumor and lymphogenous metastasis with intraglandular metastasis.
One case of surgically obtained sclerosing type showed the recurrence and death. The cystic type were enclosed by the capsule and morphologically papillary cystadenocarcinoma. The non-sclerosing type did not show the fibrous connective tissue or capsular formation and smaller compared to the above 2 types. This type suggests the early stage of papillary adenocarcinoma histogenetically.
Follicular adenocarcinoma cases were diagnosed according to the atypism of the tumor tissue and in 3 cases capsular formation was observed and in the other cases tumor tissue was directly attached to the thyroid tissue.
Metastatic thyroid cancer was found in 12 cases (3.4%) among 349 autopsy cases of the malignant neoplasia. The mode of growth was either diffuse infiltration or solitary nodular formation in the thyroid tissue.
Tumor like lesion (51cases, 10.2%) was correspond to the so-called solid cell nest and suggested the squamas metaplasia according to the histological finding of the early histogenesis.

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A new technique is described to facilitate descending thoracic aorta replacement without the use of anticoagulants. To eliminate the need of anticoagulants, tubes and cannulae are coated with nonthrombogenic polyurethane-polyvinyl-graphite (PPG). The left heart bypass employing them can provide a dry operative field. No significant changes were observed in clotting time and prothrombin time during this nonthrombogenic left heart bypass.
The following findings were observed under scanning electron microscopy: The majority of platelets were solitarily dispersed and a few platelets were aggregated in each other on the PPG-coated tube. They were uniformly spherical or spheroidal with short spiny projections and long pseudopods. Aggregations of platelets were present but metamorphoses of the platelets and formation of fibrin nets were not observed. These findings of PPG-coated tube were similar to that of uncoated polyvinyl chloride tube in heparinized left heart bypass. Moreover PPG-coated tube showed a tendency to depress transformation of platelets in early stage of thrombus formation. However, either silicone tube or uncoated polyvinyl chloride tube did not prevent transformation of platelets.
The advantages of this method over conventional left heart bypass are that the anticoagulants are not required.

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A study was made on a mode of action of the streptococcal preparation, OK-432, that is rather difficult to elucidate only in terms of its direct effect on tumor cells.
Its results are described below:
1) The survival rate of the ICR mice pretreated i.p. with OK-432 was about twice as high as in the nontreated group at 40 days after i.v. inoculation of Ehrlich carcinoma.
2) The survival rate of the C3H mice pretreated i.p. with OK-432 was more prolonged than the rate of nontreated group and post-treated group with OK-432 at 50 days after i.p. inoculation of methylcholanthrene-induced sarcoma.
3) The survival rate of the ICR mice pretreated s. c. with OK-432 was slightly prolonged than the rate of nontreated group at 40 days after i.p. inoculation of Ehrlich carcinoma.
4) The appearance of methylcholanthrene-induced sarcoma of the C3H mice pretreated i.p. with OK-432 was significantly delayed, compared with the nontreated group and the posttreated group at 80 days after injection s. c. with methylcholanthrene.
The results stated above lead to the conclusion that OK-432 has a host-mediated antitumor action.

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In the Part I, an apparent life-prolonging effect was observed in mice with transplanted tumors when OK-432 was given i. p. or s. c. as a pretreatment, indicating the presence of the host-mediated action. In this paper, the peritoneal cells were used to investigate the mechanism of its host-mediated antitumor action.
Its results are described below:
1) When OK-432 was injected into the peritoneal cavity of mice, peritoneal cells, particularly macrophages, were observed in large quantities.
2) Thus far obtained, these peritoneal macrophages demonstrated an antitumor activity.
3) These exudated macrophages were found to enclose a tumor cell in both mice and patients with carcinomatous peritonitis or pleuritis, when OK-432 was injected into the peritoneal or pleural cavity.
4) There is a tendency to protect mice against tumor rechallenge when mice are treated i. p. or s. c. with OK-432 after pre-immunization of mice with the irradiated tumor cells. Therefore, the effect of OK-432 for tumor specific immunization was suspected, experimently.
The results stated above lead to the conclusion that the host-mediated antitumor action of OK-432 is probably due to the activated local macrophages and the increased host immune reponse to the tumor specific antigen.

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Effect for the host and the tumor of the streptococcal preparation, OK-432, and Bacillus Calmette Guérin (B. C. G.) were comparatively studied.
Its results are described below:
1) Granulomatous hepatitis with giant cells was observed in 4 of 5 mice (80%) receiving 5×10⁷ B. C. G. organisms by i.p. injection. But there are no pathological findings in liver receiving the same bacterial counts of OK-432 as those of B. C. G..
2) Neutrophilia in mice receiving 4×10⁵ B. C. G. organisms i.p. is more remarkable than in mice receiving i.p. OK-432 containing 5×10⁷ streptococcal hemolyticus.
3) By administrating OK-432 or B. C. G. i.p. at the same quantity mentioned above, peritoneal cells, particularly macrophages and neutrophils, are exudated more markedly in mice receiving OK-432 than B. C. G..
4) At the same dosage, the survival rate of the C3H mice pretreated i.p. with OK-432 was more prolonged than the rate of the C3H mice pretreated i.p. inoculation of methylcholanthrene-induced sarcoma.
The results stated above lead to the conclusions that B. C. G. has a liver damage, i.e., granulomatous hepatitis as the side effect by administrating the massive dose in contrast to OK-432. B. C. G. is stronger than OK-432 as the general stimulant to the host, and OK-432 is stronger than B. C. G. as the local stimulant. And consequently the host-mediated antitumor action of OK-432 is more predominant than B. C. G. at the dose that the author investigated in this paper.

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An investigation on the helminths of wild animals (Martes melampus, Meles meles, Mustela sivirica, Myocastor coypus, Nyctereutes procyonoides and Vulpes vulpes) caught in the systems of the Chugoku mountains of Hiroshima and Okayama prefectures was done from December in 1970 to October in 1974. The worms, genus Concinnum, were found from the pancreatic duct of Nyctereutes procyonoides, Martes melampus, Meles meles and Mustela sivirica.
The parasitic rate of Concinnum in Martes melampus is 100% (the average number of parasites is about 3000), in Nyctereutes procyonoides 23.8% (40), in Mustela sibirica 20% (225) and in Meles meles 50% (9).
The parasites were fixed with Schaudin's solution while compressed between slide glasses, stained with carmine solution and observed with the light microscope. All of the worms were identified with Concinnum ten (Yamaguti, 1939) Travassos, 1944 according to the measurement.
The present paper is the first report showing that Concinnum ten was found from Meles meles and Mustela sibirica, and that these animals are also the natural final hosts of Concinnum ten.

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5-hydroxy-3-methylindole was first found by Spatz, Spatz, and Fischer in the urine of patients with centrencephalic epilepsy in 1972.
I have determined this substance in human urine by gas chromatography with an electron capture detector (ECD).
One hundred ml of urine was filtered, concentrated in vacuo and extracted by benzeneethanol (9.5:0.5v/v). The extract was passed through silica gel column.
The eluate was dried completely in vacuo, dissolved in acetonitrile, trifluoroacetylated by trifluoroacetic acid anhydride and then determined by gas chromatography (ECD). The detected peak in gas chromatogram has been confirmed as di-trifluoroacetylated 5-hydroxy-3-methylindole by GC-MS.
As the results of the experiment, it was found that about 5.5-90.0μg/day of HMI was excreted in normal subjects and extraordinary high level (108.0-613.2μg/day) was observed in epileptics.

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Mitral regurgitation following myocardial infarction is one of the most serious complications. Therefore, early detection of the mitral regurgitation occurring in myocardial infarction must help in directing a treatment for it and in improving its prognosis.
This study was conducted to establish a new clue of predicting mitral regurgitation complicated on myocardial infarction. Acute myocardial infarction and quantitatively measurable mitral regurgitation were made in 14 normal canine hearts to determine hemodynamics. Acute myocardial infarction was produced by ligating the anterior descending branch of the left coronary artery at its proximal one third and filling the branch distal to the ligation with 2%-agar solution. Mitral regurgitation was through an external shunt from the apex of the left ventricle to the left atrial appendage.
Hemodynamics were altered on production of myocardial infarction as follows: decrease of aortic and left ventricular pressures, increase of left atrial pressure and LVEDP, decrease of LV-max. dp/dt, and decrease of cardiac output and LV-SW.
Hemodynamic alterations were as follows in a heart with mitral regurgitation superimposed on myocardial infarction. Mitral regurgitation was twice as much as cardiac output of heart with myocardial infarction: increase of left atrial pressure and LVEDP, increase of total stroke volume with decrease of effective stroke volume, increase of LV-max.dp/dt, increase of aortic and left ventricular systolic pressure.
With increase of mitral regurgitation amounting 4 times as much as the cardiac output of a heart with only myocardial infarction, hemodynamics changed as follows: further decrease of effective stroke volume and LV-SW, decrease of aortic and left ventricular pressure, and no change in LV-max.dp/dt.
Analysis of the aortic and left ventricular pressure tracings revealed shortening of the rapid ejection period, resulting in reduced ratio of this period to cardiac cycle.
It was concluded that pressure tracing of the aorta or left ventricle would reflect hemodynamics altered when mitral regurgitation was complicated with myocardial infarction. Namely, it is conceivable that mitral regurgitation occurred in a patient with myocardial infarction when the pressure tracing showed shortening of the rapid ejection period. Therefore, monitoring of the arterial pressure tracing is available even in a less-equipped institute and yields indispensable information that mitral regurgitation did develop in a patient with myocardial infarction.

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Disseminated intravascular coagulation (DIC) models were made by intra-aortic infusion of thrombin (50 units/kg. body weight) during 30 minutes in the dogs.
Histological study of glomerular fibrin deposition was taken on the specimens which were collected by the renal biopsy. Changes of blood coagulation system and fibrinolytic factors of blood and urine were studied during 120 minutes.
These results were summarized as follows:
1. With the light microscope disappearance of all glomerular fibrin deposits were observed 90 minutes after initial infusion.
2. These results suggest that major mechanism of fibrin removal from capillaries was the intravascular fibrinolysis.
3. In addition, as the another mechanism of fibrin removal the transglomerular passage into urinary space was revealed.
4. Urokinase excretion in urine was reduced continuously until the end of experiment.
5. FDP was measured by serial dilution protamine sulfate test for the estimation of fragement X^O and soluble fibrin monomer complexes.

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It has been showed that the degeneration and disappearance of pulmonary surfactant is one of the causes of post-perfusion lung syndrome which occurs after cardiopulmonary bypass.
An experimental study was undertaken to reveal the change of the osmiophilic body (a precursor of pulmonary surfactant) during cardiopulmonary bypass.
Dogs were divided in 5 groups:
I. Control group
II. Group with whole blood
III. Group with 20% hemodilution
IV. Group with no blood
V. Group with 20% hemodilution and CDP-choline
Results
The following results were obtained:
1) Increase of osmiophilic bodies as ratio of the blood was increased in priming solution.
2) Increase of osmiophilic bodies in groups II, III and IV as cardiopulmonary bypass time was prolonged.
3) Osmiophilic bodies was markedly reduced by adding CDP-choline.

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Influence of surgical intervention on the immunological status of 42 patients with various malignant neoplasm was evaluated and was compaired with that of 38 patients with nonneoplastic disease.
Immune competency was measured with the percent ratio and population of circulating T-cell, which was identified based on the ability of the cell to form spontaneous rosette with sheep erythrocyte (E-rosette), and with the blastogenic activity of peripheral blood lymphocyte against phytohemagglutinin (PHA) and pokeweed mitogen (PWM). The delayed hypersensitivity was also tested by means of the tuberculin reaction.
The result was summarized as follows, mainly on the basis of the data 10 days after the surgery.
1) The percent of T-cell (E-rosette forming cell) showed no distinctive difference as compaired with that in the preoperative period, although more than the half of the patient showed some tendency to increase in the ratio, and this trend was similar with that of the patient with nonneoplastic disease. However, the absolute number of the circulating T-cell was depressed in the patient with malignant neoplasm as well as in those with benign disease, and it was particularly remarkable in the aged of the former subject.
2) The most impressive difference between pre- and postoperative situation was observed in the blastogenic response of the peripheral lymphocyte to PHA in the cancer patient. The decrease in the response of the cell down to below the preoperative level was occurred in about two third of the patient with the average of 10 percent, whereas the response in the patient of nonneoplastic disease was rather raised above the normal level in about two third of them. Though no distinctive correlation was noted between the clinical stage of the cancer and the blastogenic response, the impairement of this activity was quite striking in gastric and lung cancers of the aged over 60 years.
Furthermore, blood transfusion seemed to be against this impairement in the benign disease, but the data did not support that the similar effect of blood transfusion was working among the patients with malignant tumor.
3) The blastogenic response of the lymphocyte against PWM showed no uniform alterations following the surgery, both in the cancerous and noncancerous subjects, and the average reactivity was nearly equal to that in the preoperative condition. As for the cancer patient, the above response seemed to be not associated with difference in the disease, the age and the amount of transfused blood volume.
4) The incidence of negativation of the tuberculin reaction after the surgery was observed in 20% of the cancer patient and in 14% of the non-cancer patient. However, the available data were not sufficient to analize a correlation between the decreased blastogenic capacity of the lymphocyte in vitro and the lowered delayed hypersensitivity reaction in the skin, in association with the surgical intervention.

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The major concern of this study was to clarify how to evaluate serum lactate dehydrogenase (LDH) as one of an index to assess a therapeutic effect for malignant neoplastic disease, and also to seach for a possible difference in the quantitative and/or qualitative alteration of this enzyme according to the mechanism by which tumors loose their biological potency in the host.
In the experimental study, total LDH activity and its isozyme fraction value were determined following the complete surgical removal and ischemic necrosis of methylcholanthreneinduced mouse sarcoma.
In the clinical study, alterations of activity of total LDH and isozyme fraction III (LDH III) and IV (LDH IV) were observed before and after the treatment, as possible induces for therapeutic effects on 98 patients with various malignant neoplasm, based on the result obtained in the experimental study.
The result was summarized as follows:
1) In the tumor bearing mice, LDH activity was significantly higher than in the normal mice as had been reported by many others, and an remarkable elevation of LDH III and LDH IV was also noted.
2) Following the surgical removal of the tumor, LDH activity showed no concomitant decrease and the elevated level was maintained for at least two weeks without diminishing down to that in the normal mice, whereas LDH III and IV dropped early within the first week to that of the normal control.
3) Following the causation of ischemic necrosis of the tumor, LDH activity showed further increase temporarily in the first week and gradually decreased to the level of the tumor bearing mice by the end of the second week, and also LDH III and LDH IV descended to the normal level antecedent to that of the total enzymatic activity, but with milder slope than in the tumor-removal group. The temporary increase in these value was not demonstrated even in the early stage of the post-necrotic course.
4) The average elevation rate of LDH activity in total 98 preoperative patients with malignant tumor was 20%, and the activity was further raised even after the radical surgery for the tumor, although it returned approximately to the preoperative level by the end of the 4th week in more than half of the patient. Exceptional decrease to the normal level was observed in some of the patients with cancer of the breast and rectum, but none in those of the gastric and lung cancer.
5) The characteristic elevation of LDH III and/or LDH IV was observed among the cancer patients, according presumably to an organ-specificity from which the tumor developed. After the radical surgery, both of them lowered their activity while the total enzymatic activity still maintained the elevated level, and this occurred earlier, more precisely and with higher incidence in LDH IV than in LDH III. This trend was more clearly demonstrated in Stage II than in other stages.
6) In those who received chemotherapy and/or radiotherapy, activity of total LDH, LDH III and LDH IV showed a definite reduction with quite a few exceptional case, when a therapeutic effect was clinically manifested.

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