Cell population kinetics in the established cell line of human bladder carcinoma, T24 cells, was investigated in terms of DNA and protein synthesis during cell growth. The growth fraction was estimated to be higher than 96% in the log phase and then rapidly reduced to a final level of 2% in the stationary phase. On the other hand, the labeling index with ¹⁴C-leucine was continuously higher than 98% through the cell growth, indicating that both the proliferating and resting cells keep the protein synthesis. ¹⁴C-leucine incorporation into the log phase culture as well as into the stationary phase culture was also found to correlate well with the viable cell number. Experiments employing a cytotoxic agent again revealed that ¹⁴C-leucine incorporation satisfactorily reflected the cell viability. The results of the present work suggest that ¹⁴C-leucine incorporation can be used as a reliable measure for the in vitro assay system.

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In order to estimate fibrinolytic activity produced by human urologic malignant cells, surgical specimens from the malignant and normal tissues have been studied by a monolayer culture method. The fibrinolytic activity yielded into the supernatant medium and fibrin degradation products (FDP) resulted from coagulum lysis present in the system were determined by using a fibrin plate method and FDP assay Kit (Wellcome Reagents Ltd.), respectively. The localization of fibrinolytic activity in the cultivated cells was studied by a histochemical fibrin slide technique with a slight modification.
The results obtained were as follows:
1. An active growth of epithelial cells was observed in 11 renal cell carcinomas, a Wilms' tumor, an angioleiomyolipoma, 2 transitional cell carcinomas of the renal pelvis, and 4 transitional cell carcinomas of the bladder.
2. In the case of normal tissues, the active growth was observed in the cortex of 17 kidneys and the medulla of 4 kidneys. No active growth was observed in mucous membranes from a renal pelvis and 5 bladders.
3. Using the fibrin plate method, no fibrinolytic activity was detected in supernates from the renal cell carcinomas, the transitional cell carcinomas of the bladder, and HeLa cells.
4. The cortex and medulla released a potent plasminogen activator into the supernates; 0.20-25.36 and 1.88-5.00 CTA units/ml/1.0×10⁴ cells, respectively. The plasminogen activator was identified immunologically as urokinase type.
5. No FDP was detected in cultures from a transitional cell carcinoma of the bladder and HeLa cells after 4 day cultivation, whereas, a considerable amount of FDP in cultures from the cortex of 4 kidneys and a renal cell carcinoma in the same cultivation period; the levels were 7.5-38.6 and 4.1.μg/ml/1.0×10⁴ cells, respectively.
6. Using the fibrin slide technique, epithelial cells from the cortex of 4 kindeys in the same cultivation period showed a marked lysis of fibrin membranes in 30 minute-incubation time. The cells from a renal cell carcinoma showed less fibrinolytic activity. No lysis of fibrin membranes was observed in the cells from a transitional cell carcinoma of the bladder and HeLa cells in 180 minute-incubation time.
The physiologic and clinical significances of these findings are discussed with special reference to the combined use of urokinase and anticancer agents for urologic cancers.

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Blood pressure, plasma renin activity (PRA), sodium balance and hematocrit were measured before and a week after constriciton of the unilateral renal artery in rabbits. In some animals, urine flow and sodium output from both the constricted and the contralateral intact kidneys were estimated. Juxtaglomerular granulation index (JGI) and sodium content in renal tissue of both the constricted and the contralateral kidneys were also measured.
The following results were obtained.
1) Mean blood pressure was elevated from 113.3±7.6mmHg to 136.6±13.9mmHg by unilateral renal artery constriction. Elevation of mean blood pressure more than 25mmHg was obtained in 11 out of 20 animals. PRA was also increased to 5.16±2.63ng/ml/hr but the distribution of them was considerably wide.
2) A tendency of negative sodium balance was observed in unilateral renal artery constricted rabbits, which could be divided into two groups, animals with a negative sodium balance more than -1.50mEq/Kg/day (Group A) and the rest (Group B). The difference in sodium balance was due to the differences in both intake and output of sodium.
3) A significant positive correlation between mean blood pressure and PRA and negative correlations between sodium balance and each of mean blood pressure and PRA were observed in group A. A positive correlation between mean blood pressure and PRA was also detected but blood pressure rather closely correlated to sodium balance in group B. In many rabbits of group B, PRA was not increased but blood pressure was rather high as compared with group A.
4) There were no significant changes in hematocrit.
5) Sodium output was markedly decreased in the constricted kidneys while it was significantly increased in the contralateral kidneys.
6) JGI was increased to 72.0±37.8 in the constricted kidneys and decreased to 10.4±8.4 in the contralateral kidneys. A significant positive correlation between JGI of the constricted kidneys and PRA was detected.
7) Renal cortical sodium content was slightly decreased in both the constricted and the contralateral kidneys. Sodium content in the reanl medulla was decreased to 272.40±137.35mEq/Kg in the constricted kidneys and 266.86±116.06mEq/Kg in the contralateral kidneys. A significant positive correlation was detected between them. A significant positive correlation between renal medullary sodium content and JGI and a significant negative correaltion between medullary sodium content and sodium output in the contralateral kidneys were observed.
The results indicate that there are two types of hypertension, one of which is renin dependent one with negative sodium balance and the other is rather sodium dependent, which is present in acute stage of unilateral renal artery constriction.

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Adriamycin (ADM), an antibiotic with anti-cancer activity, was used in the treatment of superficial bladder tumors in an attempt to facilitate the transurethral operative procedure. It was expected that small tumors would be completely destroyed. A total of 80 patients were included in this trial. Adriamycin was instilled into the bladder in the following dosages: 1, 000 mcg/ml (20 or 30 mg of ADM per 20 or 30 ml physiological saline), 1, 600 mcg/ml (50 mg of ADM per 30 ml of physiological saline), and 2, 000 mcg/ml (60 mg of ADM per 30 ml of physiological saline). The two groups (1, 000 mcg/ml and 1, 600 mcg/ml) were given this treatment for 3 consecutive days and underwent cystoscopic examinations about 2 weeks later. Those patiens who showed a good response to the therapy received a second course of the same treatment. In the third group (2, 000 mcg/ml), patients received Adriamycin for 3 consecutive days twice in 2 weeks: that is, a total of 6 times in all. Cystoscopy was performed in the 3rd week from the start of therapy. In this group, the course of 6 instillations was not repeated.
The effect of this therapy was evaluated by estimating the size of the tumor at cystoscopy. A decrease in size 90% or more was designated as markedly effective, 50% or more as effective, and less than 50% as ineffective. With the 1, 000 mcg/ml dose, the result was classified as markedly effective in 2 cases, effective in 3, and ineffective in 4 (55. 6%effective rate). At the 1, 600 mcg/ml level, the result was markedly effective in 7, effective in 11, and ineffective in 7 (72. 0% effective rate). While with 2, 000 mcg/ml it was markedly effective in 13, effective in 21, and ineffective in 12 (73. 9% effective rate). The results for the whole group comprised 22 markedly effective cases, 35 effective cases, and 23 ineffective cases (71. 3% effective rate).
The effect of the therapy was then examined in relation to the site and size of the tumor, together with the histopathological finding. There were no significant differences in the results for tumors at various sites, but the therapy gave good results for tumors occurring in the anterior wall or vesical neck, and even on thumb-maize or bigger tumors, which have been considered difficult to treat. In many of the cases with solitary tumors, the therapy proved ineffective, whereas in those with multiple tumors (whether primary or recurrent), the results were more often effective. High grade papillary tumor had the lowest rate of effectiveness (5 of 9 cases, 55. 6%), while 5 of 6 cases of non-papillary tumor had effective results. The results for all low grade tumors (72. 7%) was not considered to be significantly different from the results for all high grade tumors (64. 3%). These results indicate that the therapy can be expected to be effective in high grade tumors if the disease is at a low stage.
The systemic uptake of the drug was small. One case each of the systemic side-effects of depilation, thrombocytopenia and aggravation of the ECG pattern was seen. Of . the series, 24 patients (30%) complained of bladder irritation.
In view of these side-effects, 2, 000 mcg/ml (60 mg of ADM per 30 ml physiological saline) was considered an adequate concentration of Adriamycin for this treatment.

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Changes of the rabbit ureter (central portion) following an intraluminal pressure load, especially the time course of changes during the period of hydroureter formation were studied with special reference to (1) effect of the administration of reserpine and (2) effect of aging or the difference between ureter of the newborn and that of the adult. The ureter of a rabbit after acute death was perfused with a modified tyrode solution (37±0.2°C, pH 7.2, saturated with 95% O₂+5% CO₂) in a muscle chamber. The distal end of the ureter was ligated and the proximal end was cannulated. Via this cannula, pressures of 10, 20 and 40 cm H₂O were applied for at least 4 hours. The morphological changes of the ureter were photographically recorded in chronological sequence. In the photograph, the changes of the diameter of the ureter (measured as the maximum diameter) and the length (measured on the midline) were studied. The control and reserpinized groups were compared. In the reserpinized group, 2mg/kg of reserpine was intramuscularly injected 24 and 48 hours prior to the experiment. The diameter and the length were measured before loading and the ratio between these and the values after loading were calculated.
The following results were obtained.
(1) Reserpine augmented the increase in the diamter of the ureter of adult rabbit (dilatation) at low pressures of loading, 10 and 20cm H₂O.
(2) The effect of reserpine was scarcely noted on an increase of length of the ureter of adult rabbit (tortuosity).
(3) Reserpine augmented the increase in the diameter of the ureter of neonatal rabbit (a) at earlier times and (b) at more multiple sites compared to the controls. Detailed morphological studies revealed corrugate formation in the reserpinized group compared to the balloon formation in the control group.
(4) The effect of reserpine was scarecely noted on an increase of the long diameter of the ureter of the newborn rabbit (tortuosity).

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In order to re-assess various split renal function tests designed for diagnosing renovascular hypertension, a comparative study was undertaken on 33 renovascular hypertensives, 5 renoparenchymal hypertensives and 15 patients with unilateral renal disorders. Split renal function tests were performed by a urologist as follows; under oral hydration and saddle block anesthesia, each pelvic urine was collected anaerobically through the Fr. 5 or 6 thin-walled polyethylene catheters with multiple side holes. A blood sample was withdrawn at the midst of the tests. Urinary volume per minute, Na, K, Cl, UN, Cr, and uric acid concentrations and intra-pelvic urine oxygen tession were measured. Renal vein renin ratio was determined by 2 methods, namely sequential catheterization of each renal veins by a single catheter and simultaneous sampling of each venous blood by two catheters under furosemide stimulation.
9 tests, namely the Howard 1953 method, the Howard 1962 method, the Rapoport method, the Birchall method, the Takayasu and Ogawa method, the Madeloff method, the Fournier method, the Suzuki method and the urinary oxygen tesnion ratio coupled with sodium reabsorption ratio method were performed together with determination of renal vein renin ratio.
Renal vein renin ratio obtained by simultaneous sampling of renal vein blood after furosemide stimulation showed best diagnostic accuracy. Poorest result was obtained by the Birchall method. As for prognostic accuracy, the best result was obtained by the urinary oxygen tension ratio coupled with sodium reabsorption ratio and the worst result by the Howard 1953 method and by the Birchall method.
No major complication was encountered.
Some of the split renal function tests can furnish us with valuable informations which are equal to that of renal vein renin ratio when performed under proper care.
Together with arteriography and renal vein renin ratio, split renal function studies should be performed before deciding definitive therapeutic plans on renovascular hypertensives.

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62 children and 51 adults with primary reflux were evaluated. Renal ratio (renal length/length of L2 plus its disc) of 99 refluxing kidneys of children and both kidneys of 51 adults were calculated. These values were compared to the mean and standard deviation of normal renal ratio of similar age groups, which were determined by measurement of 240 normal kidneys.
1) Cases of child: 16% of refluxing kidneys were below -2 S. D, on the initial IVPs, and most of them presented a grade 3 reflux, a grade 3 ureteral orifice and an abnormality on IVP.
76 refluxing kidneys were then followed for periods ranging from 1 to 8 years. Normal renal growth occurred in 68% through the priods (group 1). Renal ratio of 8 % declined temporarily below -2 S. D., although they exhibited accelerated growth and resumed normal renal ratio as soon sa spontaneous cessation or improvement of reflux occurred (group 2). All refluxing units exhibited spontaneous cessation or improvement belong to group 1 to 2, in which normal renal growth was observed.
Renal ratio of another 8 % were gradually deteriorated and finally became smaller than -2 S. D. (group 3). Renal ratio of 16% were persistently below -2 S. D. on initial and also on final IVP, despite the fact that half of them underwent antireflux operation (group 4). The majority of these groups 3 and 4 presented a grade 3 reflux, a grade 3 orifice and an abnormality on IVP. However, despite normal IVP or sterile urine, deteriorated renal growth were observed in some cases. 3 cases with bilateral small kidneys showed a moderate decrease in total renal function.
It is considered that -2 S. D. of normal renal ratio indicate the limit of conservative treatment and antireflux surgery is preferable, because a small kidney being for some period below -2 S. D. is unlikely to resume normal renal growth, while the small kidney exhibited accelerated growth when stopping or improvement of reflux occurred as soon as renal ratio declined below -2 S. D.
2) Cases of adult: Significant difference in renal ratio between both kidneys were commonly observed, in cases with either unilateral or bilateral reflux.
36% of refluxing kidneys were below -2 S. D. Two thirds of them were grade 3 reflux and one third were grade 2. But the majority presented a grade 3 orifice and an abnormality on IVP. 8 (34. 8%) cases of the 23, who had unilateral or bilateral small kidneys, were uremic. 4 cases associated with bilateral small kidneys were all uremic.
This study would indicate that most of small kidneys in adults are the result of gross reflux in childhood and the function of small kidney are remarkably impaired.
3) Four extremely samll kidneys removed (from one child and three adults) demonstrated microscopically almost normal nephron structure with slight mononuclear cells infiltration and the presence of partial chronic pyelonephritis. Slightly dysplastic elements (primitive ducts) were also observed in three kidneys. However, it could not be determined as to the reason why these kidneys were small: whether they were secondary to chronic pyelonephritis or congenital renal dysplasia.
Finally, it was emphasized that careful observation of renal growth is also important in management of children with reflux and they should be surgically corrected before a refluxing kidney becomes smaller than -2 S. D.

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This report is compiled from a study of 226 patients with urinary tuberculosis treated at the 18 urological clinics in the Hokuriku Area during the 6-year-period from 1970 to 1975.
The results obtained were as follows:
1) The incidence of urinary tuberculosis in urological outpatients has slightly decreased yearly.
2) The incidence as to age has gradually changed and shifted towards the population aged over 41, especially 41-50 years of age.
Sex ratio (male to female) was 1:0.78.
3) The patients with bladder symptom have decreased and asymptomatic cases have increased gradually. However bladder symptom was still the most frequent chief complaint (45.6%).
4) The right kidney was involved in 95 cases, the left in 95 cases and the both in 34 cases.
5) The patients with negative urinalysis have gradually increased.
6) Tuberculous bacilli in urine were detected at rates of 28.8 and 62.0% by microscopic and cultural examinations respectively.
7) Two hundred cases were classified into 5 groups according to the roentgenographic classification by J. K. Lattimer, the decreasing order of frequency being group 4 (55.5%), 1 (15.5%), 2 (13.0%), 3 (10.5%), 0 (5.5%).
8) The typical cystoscopic findings of the patients complicated with tuberculous cystitis were not so frequent.
9) There were only 5 cases with renal failure with BUN over 40mg/dl.
10) There were 53 cases (30.3%) with accelerated ESR over 41mm (1 hour).
11) Tuberculin skin test was positive in 20 of 24 cases tested (83.3%).
12) The majority (66.4%) of chemotherapeutic regimens used were the combination of streptomycin, PAS and isoniazid.
13) Nephrectomy has been done for 131 cases in addition to chemotherapy.
14) Eight cases died for this period because of 2 renal failure, each heart failure, acute pneumonia, cerebral infarct, carcinoma of rectum and 2 unknown causes.

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The patient was a 69 years old male with chief complaints of miction pain and lower abdominal pain.
Two tumors were found by cystoscopic examination, one of them was at the bladder apex and another was near the orifice of the left ureter.
Partial resection of the bladder wall was performed. Histopathologically the former tumor was with marked fibrosis accompanied by microabscesses and colonies of fungus, and the latter was a transitional cell carcinoma.
We suspect actinomycosis of the urachus from the position and appearance of the tumor at the apex but the way of infection is unknown.

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