Immunological and pathological observations on the experimental nephrotic syndrome were made in this paper. The relationship between the change in the epithelial cells of glomerular capillary and mechanism of proteinuria was studied.Results obtained are as follows: 1) By the injection of anti-ratkidney rabbit serum, proteinuria appeared within 1 to 3 hours. The most remarkable proteinuria was observed about 24 hours later. In this case, the pathological status of the kidney was just like the nephrotic syndrome with nephritis by means of the blood chemical and histological examinations. 2) Following the injection, the 1st reduction or disappearance of the complement activity took place 1 to 3 hours later. The 2nd reduction or disappearance of the activity occured 2 days later and continued for 7 days. This evidence is so called the two phase reaction. 3) By the electronmicroscopic investigation, no significant change in the glomerular structure was observed within 24 hours following injection. However, 3 days later, desquamation of the epithelial cells was observed. Lamina densa was dispersed to some degree. Microvilli of the epithelial cells increased and the changes in the structure of foot processes were observed to some degree. 4) The 1 to 2 weeks following the injection, nephrotic syndrome appeared clearly. Variable sizes of vesicles appeared in the epithelial cells and desquamation of the cells was significant. The basement membrane appeared to be non-uniform and dispersed. Flatness of the foot processes was significant and their structure had disappeared. Endoplasmic reticulum, Palade granules and microvilli increased in the epithelial cells. The destruction of the basement membrane was predominent at the place where the foot processes had disappeared. 5) In the rabbits with marked proteinuria produced by the long term egg alubumin load, no change in the epitherial cells was observed. Conclusions: The 1st reduction of the complement activity may be caused by the antigenantibody reaction which occurs between kidney tissue and anti-ratkidney rabbit serum. And the 2nd reduction seems to be due to the effect of different species of protein. In the case of this study, the epitherial cells may work as an antigen. From the evidence described in the result No. 5, it may be conclueded that the change in the epitherial cells is essential to the nephrotic syndrome and it is not due to the passage of the large amount of protein through the glomerular capillary wall.

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Many investigators have tried to produce experimantally chronic nephritis which eventually progresses to kidney atrophy simulating that of human beings but as yet, there has not been a successful case. Sarre and Wirtz found that by injecting nephrotoxin into the auricular vein of rabbits and when one artery is ligated for 15 minutes the kidney whose artery was ligated was not affected by nephritis as compared to the other side. Pressman et al, discoveredthat the anti-kidney serum which was labeled with I¹³¹ disappeared from the blood stream in 18 minutes. These results suggest that if nephrotoxin nephritis progressive in nature, chronic nep-hritis or kidney atrophy is sure to occur. So, the following experiments were tried to make chronic nophritis or contracted kidney, modifing Sarre's original method. On the other hand recently many reports have been published on renal hypertension due to unilateral renal diseases, such as stenosis of the main renal artery or chronic pyelonephritis. This paper also concerns the observation of changes in the blood pressure in unilateral chronic nephritis. The follwing method was used in making the right unilateral nephritis in rabbits. The left renal artery was exposed from the back. As soon as the renal artery was ligated at two points with fine silk thread, 2.5 cc/kg of nephrotoxin was injected rapidly into the auricular vein. Twenty minutes after the injection the thread was removed terminating the operation. Three control groups of 1) the usual nephrotoxin nephritis, 2) ligation of the left renal artery for 20 minutes, 3) rignt unilateral nephritis post left nephrectomy. The blood pressure, urine analysis and serum urea nitrogen were observed carefully in all groups. S^ix to 165 days later the kidneys were examined for pathological findings. Results were as follows:1) Sustained renal hypertension did not occur in this experiment.2) No pathology was found in the left kidney.3) The right kidney atrophy with granulating surfaces in most cases were observed in to 20 cases survivtng for 30 days after operation.4) Histologically the gromerulus, tubules and interstitial tissue were found to be similar to the changes occuring in human chronic nephritis and kidney atrophy but the findings in the vascular system were considerably different. The areterioles especially the distal portion of the interlobular arteries showed remarkable elastosis and intitimal thickening though there were no changes in the vas afferens. Acute degeneration, necrosis and arteritis were not observed.5) Some pathologial findings stated above were seen in those surviving for 30 days and all changes were noted in those surviving over 90 days.6) None of the changes were observed in thec ontrol groups. This method of producing experimental chronic nephritis seems to be the best, for it is possible to reproduce chronic nephritis and kidney atrophy with severe uascular changes in almost 100% of the cases. It is believed that this method is the best way available for the study of chronic nephritis.

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As it is well known that anatomically the vascular changes in hypertension are most pronounced in the arteries within the parenchyma of the kidneys, observations were made on them by renal biopsy and their relations to age were studied in 52 cases of arterial hypertension from 18 to 72 years of age. The vascular changes were represented by the sclerotic change and narrowing index (inside diameter/outside diameter-ratio) of the wall in each of the three sections: arterioles (below 50μ), prearterioles (51-90μ), and small arteries (91-200μ). Changes of glomeruli, inters ti-tium of cortex, and proximal tubules also were refered to. Followings were the results. (1) In each section, between the sclerotic change and the narrowing index there were found-marked parallel correlations. When there was no sclerosis of the wall its narrowing index was above 0.4, while in advanced sclerosis it was below 0.33. (2) Two adjacent sections of the arteries were significantly correlated in the degree of sclerosis and narrowing each, while between arterioles and small arteries, which are not adjacent to each other, no correlations were seen when the lesions were far advanced. From these findings, the histological changes of the small (in broad sense) renal arteries in hypertension are supposedd to be classified into two types, the predominant arteriolar and the predominant small arterial. (3) The sclerosis of the prearterioles and small arteries was intensified with age. On the other hand, most pronounced change of the arteriolar sclerosis was found in 40 to 59 years of age. The narrowing index was increased with age in only small arteries. (4) In the predominant arteriolar type, the sclerosis of arterioles was found almost in the cases under 60 years of age with increasing intensity with age, while in the predominant small arterial type it was observed mostly in the cases over 40 years of age with decreasing intensity after 60 years of age. (5) From above observations, it is presumed that the effecting causes in these two types of sclerosis are not identical. (6) Of our patients, sclerosis of the arterioles was not found in thirty per cent, of whom eighty per cent were under 39 years of age.

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In the first report of this study the histological features of the arterioles, prearterioles, and small arteries of the kidney between the renal vascular lesions and blood pressure, renal functions, electrocardiographic changes, and retinal findings are studied. The results were as follows: (1) Histological changes in arterioles and prearterioles were closely correlated to the systootic and diastolic blood pressures. Put there were some cases without recognizable histological changel, which means that the elevation of blood pressure precede the vascular change. Puls pressure had significant correlations with the histological changes in every section of renal arteries. (2) RPF was closely correlated to the histological changes in every vascular section. In 70 to 30 per cent of the cases without and with slight vascular change RPF was in normal range, while 60 to 70 per cent of the cases with moderately and far advanced vascular change showed diminished RPF. (3) GFR was loosely correlated to the sclerotic changes in the arterioles and the prearterioles. In the presence of slight or moderate vascular changes GFR was maintained in the normal range. (4) FF was generally elevated with the vascular change, especially with the narrowing of arterioles and prearterioles, but was decreased when the narrowing index was beyond 0.3 (where FF was about 0.3). (5) The total renal vascular resistance was increased in correlation with the histological change in every vascular section: closer with narrowing than with narrowing and closer in arteriolar section than in preateriolar and small artery sections. (6) Retinal findings according to Keith-Wagner's classification were significantly correlated to the sclerotic change of prearterioles and small arteries and the narrowing index of small arteries. (7) The value of Sv₁+Rv₅ in electrocardiographic findings increased with the arteriolar changes and decreased in negative correlation to the changes in the small arteries. Appearance of abnormal STT were significantly correlated of the sclerosis and narrowing of the small arteries. In summary, it is concluded that in arterial hypertension there exist more or less close relationships between the histological changes of the arteries within the renal parenchyma and age, blood pressure, renal functions, cardiac involvement, and retinal findings in the pathogenesis, pathological physiology, and progress of this disease.

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For the purpose of clarifying the relation between the minute structure in the tubular cells and its enzyme activity, succinoxidase system activity (S-O system) and DPN diaphorase system activity (DPN system) were determined in normal rabbits, oligemia-induced rabbits and substancesloaded rabbits, using cell fractionation procedures and histochemical techniques. 1. In the normal rabbits, S-O system activity was greatest in the distal renal tubule and Henle's ascending limb. The S-O system was also present in a part of the proximal renal tubule and collecting tube. The DPN system was found in the proximal renal tubule, callecting tube, distal renal tubule and Henle's limb. Both enzymes showed the greatest activity in the mitochondria fraction and therefore they were equally present in mitochondria in the above-mentioned regions. 2. Diabetes was induced in rabbits by intravenous injection of 2 mg of phlorizin per kg of body weight. Each fraction underwent no marked changes in the S-O system, while it showed a slight increase in the DPN system. But neither locality of enzymes nor changes in enzyme activity were observed in the histochemical specimens of both systems. 3. In rabbits which were loaded with 40cc of 50% glucose, the remarkably increased activities of the S-O and DPN systems were seen in each fraction. This was prominent in the cells of the proximal renal tubules that is, it seemed that these enzymes played a major part in the tubular reabsorption of glucose. 4. Oligemia was produced in rabbits by using a clamp on the artery of one kidney, and a comparison with the control kidney was made. In the oligemia-induced kidney both enzymes showed a considerable decrease in activity. 5. Rabbits were injected intravenously with 2 g of egg-albumin per kg of body weight, and enzyme activity was measured 20-40 minutes after the appearance of proteinuria. The activities of both enzymes in the droplet 3 and 12 hours later were ascertained in accordance with the method of Straus. Twenty to 40 minutes after proteinuria occurred, an increase in the activities of bothh enzymes was observed in the mitochondria and microsome fractions. The S-0 and DPN systems in the droplet exhibited a decrease in activity 3 hours after proteinuria developed. A decrease in the activities of both systems became more prominent 12 hours later. These changes were recog nized in the cells of the proximal renal tubule. In other words, the division of mitochondria occurred in the early stage of protein reabsorption, with a result of an increase in their number and hyperfunction of the cells. But the activities of both systems showed a decrease along with droplet formation.

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A study was made on effects of various drugs on the changes in renal circulation by cold pressor test which was performed to clarify the regulatory mechanism of renal circulation under stress. Cold pressor test (dry ice methoe) was performed on adult mongrel dogs. The effects of the cold pressor test on the blood pressure and renal clearance were studied as control experiment, and following intravenous administration of hexamethonium (5mg/kg of body weight), reserpine (0.5 mg/kg), chlorpromazine (5 mg/kg), 1-hydrazinophthalazine (4 mg/kg), veratrum (0.025mg/kg) and methylhexabital (30mg/kg), cold pressor test was again performed on the animals a week later to review the previous findings. The results were as follows: During the cold pressor test, the dogs that were not administered with the drugs showed an increase in blood pressure, a decrease in renal plasma flow, glomerular filtration rate and an increase in tolal renal vescular resistance. 2) To this effect of the cold pressor test, definite inhibition was noted upon administration of C₆, moderate inhibition seen in the case of chlorpromazine and the tendency of slight inhibition was recorded when reserpine was used. 3) Hydrazinophthalazine, veratrum and methylhexabital showed no significant inhibition to the changes in renal clearance values induced by cold pressor test. From the above findings that the effect of the cold pressor test was inhibited by drugs which block the sympathetic system it was considered that the sympathetic system plays primary an important role on the regulation of renal circulation under stress and, further from the results on methylhexabital, no definite relation was obserued between the reticular formation and reactive system of cold pressor test in the case of given dosage.

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In order that the influence on the renal hemodynamics given by bleeding and reinfusion of lost blood (30 and 60 minutes after bleeding) might be clarified, changes in renal blood flow of 18 dogs were measured with electromagnetic flow meter. The results were as follows: 1) In bleeding, increase in renal vascular resistance and decrease in renal blood flow were observed accompanied by the fall in blood pressure. When blood pressure fell to 22-65 per cent of the control value by bleeding, renal blood flow decreased to zero or near zero. As compared with fall in blood pressure, rate of decrease in renal blood flow was more remarkable. Bleeding blood volume needed for renal blood flow to decrease to zero was 13-47 per cent of whole circulating blood volume, and the relationship between bleeding speed (20-60 cc/min) and bleeding blood volume or degree of fall in blood pressure was not significant. 2) When the whole lost blood was reinfused 30 minutes after bleeding, in three cases out of five, definite decrease in renal vascular resistance and increase in renal blood flow were accompanied with the rise in blood pressure. Two cases showed only a slight decrease in renal vascular resistance and a slight or almost negligible increase in blood flow with rise in blood pressure. 3) When the whole lost blood was reinfused 60 minutes after bleeding, decrease in renal vascular resistance and increase in renal blood flow were accompanied with rise in blood pressure. But one case showed increase in renal vascular resistance and decrease in renal blood flow in spite of a considerable rise in blood pressure. Bleeding caused a marked constriction of renal blood vessel, and showed a marked decrease in renal blood flow in company with the fall in blood pressure. There was not much difference in the degree of restoration in renal blood flow whether reinfusion was made after 30 minutes or 60 minutes.

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To find the clinical meanings of serum sialic acid (SA) in glomerulonephritis and nephrosis, it was estimated in 94 patients with diffuse glomerulonephritis, in 8 patients with nephrosis, in patients with other diseases and in healthy subjects and its relationships to the clinical andd pathohistological findings were studied. The method used was the Ehrlich's direct reaction using p-dimethylaminobenzaldehyde reported by Werner and Odin. Results were as follow: 1) Normal level of serum SA ranges from 32.5 to 71.0 mg/100ml with a mean of 52.7 mg/ 100ml. In the patients with rheumatism, tuberculous pleurisy, cancer, inflammations, nephrosis, glomerulonephritis and hypertension, SA levels were significantly elevated, whereas in liver cirrhosis they were lower. 2) In glomerulonephritis, in general, serum SA was higher than normal at its initial stage, once decreased towards 10 days after the onset of the disease, and gradually elevated again from one month after the onset to a second peak situating about 3rd month which was followed by a declining to normal level at 4-6th month. On an average, SA level was highest (68.3 mg/100ml) in subacute stage, in acute and chronic stage being somewhat lower (64.9 mg/100ml, and 61.8 mg/ 1OOml, respectively). 3) The first peak of this trend of serum SA level in glomerulonephritis is supposed to be associated with the preceding infection, the second with repair of renal tissues. 4) Roughly saying, serum SA levels were generally higher in the cases with severe histolic renal damages, especially in subacute stage. 5) Considering from the feature of serum SA and histological and clinical findings, acute and excerbated glomerulonephritis should be regarded active and be managed as such for 6 months at least. 6) Markedly elevated levels of SA were found in 8 cases of lipoidnephrosis with a mean of 82.3mg/100ml. They were especially higher when edema and marked albuminuria existed. 7) In 45 hypertensive patients, too, serum SA levels were significantly higher than normal (mean 62.Omg/1OOml), especially so in patients with albuminuria. 8) In general, serum SA level was higher with the impairment of renal functions. 9) In glomerulonephritis, serum SA level ran almost parallel with blood sedimentation rate, but the former was more sensitively correlated to the clinical course. Anti-streptolysine-O titer was also in parallel to SA level in rheumatism, but in glomerulonephritis the curves crossed each other. 10) There were significant positive correlations between serum SA level and blood pressure in glomerulonephritis and hypertension. 11) In inflammatic diseases the serum SA tends to decrease in convalescence.

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In the previous paper the clinical meanings of serum sialic acid (SA) in glomerulonephritis and nephrosis were reported. In this paper similar researches were made on the urinary SA. Estimations of the urinary SA were carried out by a method modified by the author. 1) By using cation resin (DAWX W50 X 8) column in the preliminary procedure of urine, most parts of urochromogen which interfere with the reaction were almost completely excluded. This procedure can afford a useful clinical method to determine the urinary SA. The urinary SA determined by this method was supposed to be a polymer different from that in sera. 2) Urinary SA concentration was not always high in glomerulonephritis, and was not in any direct correlation with the stages or degrees of histological damage. However, its urinary daily output was often greater in severe cases of acute and subacute stages. 3) It seems to be very important to investigate the urinary SA outputs along with the clinical course. In every stage, acute, subacute or chronic of glomerulonephritis, the daily output was greater in the early phase of treatment and was gradually decreased, though not continuously. In chronic stage, it was relatively small, especially smaller in fatal cases. After tonsillectomy some cases showed increased outputs. 4) In nephrosis, compared with glomerulonephritis, both urinary concentration and daily output of SA were strikingly greater. They were remakably increased in edematous stage and decreased with clinical healing. 5) In the cases of marked albuminuria (above 20mg/dl) in glomerulonephitis and nephrosis, the concentration and output of urinary SA were roughly correlated to those of protein in the urine, respectively. 6) In nephrosis and glomerulonephritis with marked albuminuria, excretion of SA into urine seems to be effected mainly by the leak of sialoprotein accompanying to albumin. It is suggested, however, that the SA clearance and its local discharge from the renal lesions must come into further consideration.

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