The purpose of this study is to analyze the function of renal medulla applying a mathematical model of simple countercurrent system. The simple countercurrent system may be expressed as follows:
C=C_oexp (kx/au),
where C is the final osmolality in countercurrent system, C_o is the inital value of the osmolality, k is the rate constant of solute transport from ascending limb to descending limb, x is the length of the system, a is the crosssection of the tubule, and u is the velocity of fluid in the system.
Assuming that the urine osmolality and urine flow is proportional to the final osmolality in the countercurrent system (C) and to the fluid flow (au), rerpectively, the following relation may be expected :
U_osm=C_oexp(const/V)
where U_osm is the urine osmolality, V is the urine volume The following study was perfomed comparing the results obtained from clinical and animal experiments to the theoretical relation, and the following results were obtained.
(1) Experiments of the mongrel dogs, under water and osmolar (mannitol) diuresis, demonstrated that the relation of urine osmolality to the urine volume is identical to that expected from the theoretical equation. When hydrochlorothiazide is infused simultaneousaly, the change of the relation occurs in such a manner of increasing the initial osmolality of the urine (C_o). Therefore, this compound seemed to have its reaction site in the renal tubules other than Henle's loop.
(2) Fishberg's urine concentration and dilution test were performed in the patients with cirrhosis of the liver (6 cases), chronic glomerulonephritis (10 cases), chronic adrenal insufficiency (1 case), and in 5 healthy adults. As the osmolar load to the nephron can be considered to be constant in this experiment, the equation becomes :
U_osm=N/Vexp(const/V)
where N is the osmolar load. The reasonability of this equation was confirmed in each group of the patients.
In cirrhotic patients with marked asceites, as the urine volume did not increase significantly, the dilution of the urine did not occur substantially. In patients with moderate to svere renal damage, the relation of urine osmolality to urine volume was appearently different from those of normal and cirrhotics. In these cases, urine flow from each nephron may increase to an extent which can be calculated from the decrement of the glomerular filtration rate. When urine volume was corrected for decreased GFR as follows:
corrected V=V⋅GFR_normal/GFR_patient
the relation of urine osmolality to the corrected urine volume showed a fair agreement with those of the normal and cirrhotics. Therefore, the failure of urine concentration and dilution in the pationts with decreased renal function may be the result of increased urine flow in the countercurrent system.
In a patient with chronic adrenal insufficiency, the results of the experiment were similar to those of chronic glomerulonephritis. As the functioning nephron did not diminish in such a case, the same explana-tion could hardly be applied. In order to clarify this point, an experiment of acute constriction of renal artery was performed.
(3) To dogs with constricted right renal artery, a hypotonic solution (1.8% glucose, 1.2% mannitol and 0.05% saline) was infused. In most instances, the urine from the constricted kedney showed some-what lower osmolality than that of control. As the number of the functioning nephron did not decrease, the defect of urire concentration and dilution should be a consequence of decrement of osmolar load to each functioning nephron resulted from the GFR reduction. When the urinary osmolality was corrected for decreased GFR as follows :
corrected U_osm=U_osm⋅ GFR_normal/GFR_experimental

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In an attempt to study the distribution of water and electrolytes and the permeabilities of Na and K of the rat kidney tissue, the experiments were performed by means of a slice analytical technique and of a radioisotope tracer method. The results were obtained as follows:
1. Water content of the medulla under the varied conditions was usually larger than that of the cortex, and was the osmotic concentration increased towards the papilla tip, NaCI and urea concentration gradients between the cortex and medulla were more predominant, especially in the antidiuretic stage. There was no evidence to indicate that potassium contents in the kidney tissue were varied under the different conditions.
2. Using radioactive isotopes Na²⁴ and K⁴², the measurements of rate constant and turn-over rate were performed.
(i) Rate constants towards both directions (kin andtCout) were calculated by the three compartmentt analysis. Normal controls were measured and also the effect of 1 mM DNP on each rate constant was observed. Significant effect of DNP on Na rate constant was depression of kout in the medulla and on K rate constant was decline in kin of both the cortex and medulla.
(ii) Turn-over rate was studied by means of radioactive materials and the half time (T_1/2) was calculated by the Na²⁴-washout experiment, whereas the twice time (T₂) was obtained by the K⁴²-uptake experiment. Effect of DNP on the Na²⁴-washout showed moderate prolongation of the slower component of the cortex, but no significant changes of the others. Moreover, effect of DNP on K⁴²-uptake showed significant prolongation of the slower component of both the cortex and medulla.
(iii) In the Na²⁴-washout experiment, low sodium concentration of washout solution induced significant prolongation of the slower component of both the cortex and medulla. In the K⁴²-uptake experiment, low potassium concentration of medium (1.5 mEq/L) induced prolongation of the fast component and shortening of the slower component, especially the slower component of the cortex. On the other hand, significant shortening of the fast component and no significant change of the slower component of both the cortex and medulla were observed in high potassium concentration of medium (26 mEq/L).

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In order to elucidate the mechanisms of hypercholesteremia in the nephrotic rat, the rate of acetate-1-¹⁴C incorporation after the induction of nephrosis. Nephrosis was induced in adult male rats of the Wistar strain by injection of anti-rat kidney serum according to the method of Heymann and Lund. Cholesterol synthesis in nephrotic liver slices was remarkably increased, for example, up to 11.8 times than normal at the fourth week after the onset of nephrosis. Hypercholesteremia in nephrotic rats can best be explained on the basis of the present result ; the increased hepatic cholesterol synthesis.

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The open renal biopsy was carried out on the seven one-side nephrectomized Kidney with chronic Pyelonephritis. The renal function by dint of renal clearance and P. S. P. test before and after the biopsy showed the post operative decrease of RPF, more considerably than GFR, and its delayed recover, so that one observed the tendecy of F. F. iecrease, which mostly recovered after 34 weeks, except a complication case of perinephritis with an exhancnment of GFR, RPF and RBF, that might be caused by the influence of perirenal attack. Measuring the urinary Cl, Na, K excretion of three without macroscopic hematuria at 4 th, 8 th, 12 th hour after the biopsy, the urinary volume as well as Cl, Na excretion were diminished for a while K increased after temorary decrease. So was slight the influence of the open renal biopsy towards the one-side nephrectomized patients, so that the biopsy is considered safely feasible to them.

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It is well known that a few endothelial cells of the glomeruli accumulate a large quantity of fine particles or colloidal substances, such as carbon black, cholesterol, methyl cellulose, alcian blue, and trypan blue, when they were introduced in blood. This investigation was attempted first to compare the phagocytic activity of these cells with that of the members of reticuloendothelial system, and second to examine the role of them in normal and pathological conditions of the glomeruli. The materials were 7 normal and 23 unilateral Masugi nephritis rabbits. Vital staining was performed by the intravenous injection of carbon black suspension (25% dilution of Pilot black ink). The normal rabbits received 1 or 3 injections of 5 or 10 ml/kg of the suspension. They were killed 1, 2, 3, and 24 hours after the last injection. Unilateral Masugi nephritis was produced by a single injection of 1.25 ml/kg of duck anti-rabbit kidney serum during the transient ligation of the left renal artery. Clinical course of the disease was divided into five stages ; latent (within 5 days after the injection), initial (6-7th day), severest (8th day), lasting (10-2lth day), and healed stage (21-66th day). At each stage, some of the animals were sacrificed, receiving intravenous injection of carbon black suspension (10 ml/kg) 24 hours before the sacrifice. Further 3 nephritic animals were injected with daily dosis of 30 mg of predonisolone for 1, 2 or 3 days before the sacrifice at the 8th, 9 th or 10 th day after the injection of nephrotoxin, respec-tively. They also were vitally stained 24 hours before the sacrifice. Light-microscopic studies were performed on the kidney, liver, spleen, bone marrow, adrenal glands and hypophysis. The results obtained were as follows ;
1) In vital staining of the norma rabbits, four kinds of cells were differentiated in glomerular tufts : (i) glomerular epithelial cells negative to vital stain, (ii) common capillary endothelial cells, nearly or perfectly negative, (iii) mesangial cells, weakly positive, (iv) phagocytic endothelial cells, markedly positive. The ratio of the number of the latter three kinds of cells was as follows, mesangial cells 53.3%, common endothelial cells 46. 2%, and phagocytic endothelial cells 0.60.
2) When the phagocytic activity of the glomerular phagocytic endothelial cells and of the members of the reticulo-endothelial system was compared, the former seemed to take the carbon black after the blockade of the latter.
3) In the glomerular tufts of the Masugi-nephritis, there were found the phagocytic endothelial cells, common endothelial cells, mesangial cells, and endothelium-like cells. The phagocytic endothelial cells appeared in all stages, except for the severest stage. They were, however, small in number, and did not play an inportant role in the development and progression of the disease. The phagocytic activity of the common endothelial cells was nearly similar to that in normal condition. The activity of the mesangial cells was markedly enhanced. The endothelium-like cells were syncytial and frequently transformed into multinuclear giant cells. The cytoplasm was stained basophilic and contained numerous filament-like structures. Their phagocytic activity was not uniform. Some of them took no carbon granule, some took various amount of granules which were frequently arranged in rosette-like pattern. From the histologic findings of the nephriticc rabbits treated with predonisolone, it was suggested that these endothelium-like cells were originated.d from mesangial cells.
4) The large "endothelial cells" appeared in the nephritic glomeruli were not a single kind of cells. In the stages soon before and after the onset of the nephritis, the majority of them were the common endothelial cells, and in the severest stage, the endothelium-like cells. In the lasting stage and thereafter, they were composed of miscellaneous ; namely degenerating endothelium-like clls

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Carbon disulphide (CS₂), which has been used in the production of viscose rayon, is hazardous to workers exposed to it, After World War II, chronic poisoning with CS₂ has been reported in Italy and Switzerland to cause the arteriosclerotic changes of the brain and the nodular glomerulosclerosis of the kidney.
In this country, however, these types of CS₂ poisoning have not been reported. The author and co-workers found 13 cases of CS₂ glomerulosclerosis in the workers of a viscose rayon factory (1964).
The purpose of the present paper is to reveal the incidence, the mode of the development and the pathogenesis of CS₂ nephrosclerosis by mass survey. The materials were 402 workers of a viscose rayon factory. They were divided into 5 groups as follows; spinners and bleachers (group A), repairmen of spinning and bleaching machines (group B), CS₂ makers (group C), members of laboratory (group D) and viscose makers (group E). Group A had the most chances to be exposed to CS₂ vapor and the chance decreased in the other groups in the order described above.
Urinary protein was examined in every worker. Blood pressure, total serum protein and total serum cholesterol were measured in 258 workers, serum esterified cholesterol and electrophoretic pattern of serum protein, serum lipoprotein and glycoprotein in 200 workers. The results obtained were summarized as follows;
1) Albuminuria was found in 16 workers (10%) of group A, in 7 (12%) of group C and in 3 (2%) of group E. In groups B and D no albuminuria was found. On the severity of albuminuria, it was _??_-_??_ positive in 12 cases of group A. In group C, it was ±-+ positive in 6 cases and was temporary in 3 cases of them.
2) Eleven workers with albuminuria of group A were renal-biopsied. Histological examinations revealed diffuse glomerulonephritis in 1 case, nodular glomerulosclerosis similar to Kimmelstiel-Wilson syndrome in 7 cases (severe form in 2 cases, mild form in 2 cases and initial form in 3 cases) and diffuse glomerulosclerosis in 3 cases.
3) These 10 workers with glomerulosclerosis and 3 patients, who were already dead and showed nodular glomerulosclerosis in renal biopsy, were clinicopathologically studied. They all belonged to group A and their service in this department reached 8-21 years. The incidence of the disease in group A was 8%. They were relatively young (30-49 years old). Funduscopic examination often revealed microaneurysms, punctuated hemorrhages and white spots. Blood sugar level at the fasting time and in the oral glucose tolerance test was normal in every patient. From these findings, it was concluded that they were suffe-ring from CS₂ nephrosclerosis.
4) Serum total cholesterol level in group A (201+45.4 mg/dl) was significantly higher than that in group C (165+8.66 mg/dl) and in group D (190+40.1 mg/dl). There was no significant difference of it between group B (182+28.4 mg/dl) and other three groups, The ratio of esterified to total cholesterol in group A (66.8±6.99%) was significantly lower than that in group B (69.9±3.15%) and in group D (69.8±8.34%).

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It was already reported by many investigators that diminished excretion of 17-OHCS in urine and increased accumulation of conjugated 17-OHCS in plasma were sometimes seen in patients with impaired renal function. In view of only few studies put emphasis on adrenal function in renal diseases, the author investigated in this study, laying stress on this point. Patients were as follows : 13 with subchronic glomerulonephritis, 14 with chronic glomerulonephritis, 18 with lipoidnephrosis and nephrotic glomerulonephritis (nephrotic syndrome), 4 with chronic pyelonephritis, 3 with benign nephrosclerosis, 2 with renal lesion in SLE, and 1 with primary amyloidosis. These 55 patients were intramuscularily injected 40 i. u, of ACTH-Z for 3 days. Adrenal function and relation-ship between renal function and 17-OHCS in plasma and urine were investigated. The following results were obtained. 1) There was no correlation between GFR and free 17-OHCS in plasma. It was generally agreed that free 17-OHCS in plasma was most reliable as the index of adrenal function. According to the reason above mentioned, free 17-OHCS in plasma might be considered as the same index even in renal diseases. 2) In patients with subchronic glomerulonephritis, chronic pyelonephritis, renal lesion in SLE and primary amyloidosis, the adrenal function was within normal limits. 3) In 14 patients with chronic glomerulonephritis, 12 had normal adrenal function, but 1 showed adrenal hoperf unction, and 1 was suspected having hypof unction. 4) In 9 of 18 patients with nephrotic syndrome, hyporeaction for ACTH was recognized. But it was not clear in this study whether there was slight decrease of adrenal reserve function or not, whether it was related to low concentration of transcortin due to hypoalbuminemia, or whether it was concerned with other factors. 5) In 1 of 3 patients with benign nephrosclerosis, slight hyperreaction for ACTH was seen, but any conclusion could not be drawn because of only few cases. 6) There was negative correlation between conjugated 17-OHCS in plasma and GFR only on the second day of ACTH administration. Namely, on the occasion of highly advanced renal failure, the tendency of accumulation of conjugated 17-OHCS in plasma was seen according to increased concentration of conjugated 17-OHCS in plasma.7) There was positive correlation between GFR and total 17-OHCS in urine on the control day, on the first and second day, and also positive correlation between GFR and free 17-OHCS in urine on the first to third day of ACTH administration When GFR was decreased below 20 cc/min., the possibility that total 17-OHCS in urine might decrease below normal limits, even if adrenal function was normal, was recognized.

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