Continuing our studies on the biochemical and histochemical distribution of fibrinolytic activity in the various epithelial cells, we wish to report comparative observations on the localization of tissue plasminogen activator in the normal bladder wall of mice, rats, guinea pigs and rabbits which are widely used in experimental studies using the histochemical fibrin slide techniqe.
A few similar histochemical comparative study deals with rat and human bladder wall. Such a study is of particular interest because the transitional epithelium cells of urinary tract has a special role in physiology of fibrinolytic systems.
In all instances, the same sequence of fibrinolytic activity was demonstrated, rats and guinea pigs being highly active, rabbit less so and mice only weakly active; the fibrinolytic activity was found in relation to some vessels in the muscular coat or the submucosa, the transitional epithelial lining and the desquamated cells of all animals studied. These findings were practically similar pattern with the localization of fibrinolytic activity in the bladder wall of rat and man as described recently.
It was also found that the bladder wall can be stored at least one month under keeping in sealed plastic bags to prevent evaporation at temperature of -20°C or lower without significant loss of fibrinolytic activity, although the prolonged storge in the refrigerator to which the bladder had been exposed has had a slight disturbing effect on the epithelial cells.
The fibrinolytic activity in the bladder wall was not produced by a direct effect of fibrin splitting protease, and it indicated that the pronounced lysis of the plasminogen-rich fibrin demonstrated in all animal species studied was caused by a plasminogen activator released by the bladder epithelial cells and vascular endothelial cells.
The position of plasminogen activator at the bladder epithelial cells would suggest that the urinary tract is protected itself from urokinase which is fibrinolytically very stronger and fibrinolysis at the bladder epithelium could assist in removeing fibrin or foreign bodies deposits which produce a nucli of urinary calculus in pathological conditions.
The serection of the preffered laboratory animals except mouse in experimental studies of reparative bladder epithelium formation could perhaps be explained by the similar pattern of fibrinolytic activity in its tissues.

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Plasma renin activity (PRA) and plasma angiotensinase (ATase) activity were measured in 3 patients with acute renal failure, 36 patients with chronic renal failure, 75 control patients with various types of hypertension or urological diseases, and 12 normal control subjects as well as in 18 dogs which were performed bilateral ureteral ligation, bilateral nephrectomy and control operation.
The results were as follows:
1) PRA was increased significantly in the bilateral ureteral ligation group and was undetectable in the bilateral nephrectomy group of dogs. Plasma ATase activity in these two groups showed no significant difference from that in control group.
2) PRA was increased remarkably in 9 cases of renovascular hypertension and pyelonephritis in man. Other control groups rarely showed increased PRA. All of control groups were without marked by increased plasma ATase activity.
3) In 8 cases of human renovascular hypertension, control renal venous renin activity was significantly higher than normal cntrol or peripheral venous renin activity. There was no remarkable difference in plasma ATase activity. PRA was increased significantly by sodium depletion but plasma ATase activity was unchanged.
4) PRA in human acute renal failure was increased markedly during oliguric phase and returned to normal values during diuretic phase and was again increased during recovery phase. Plasma ATase activity was increased slightly only during diuretic phase. However, no definite conclusions were war ranted due to the insufficient number of examined cases.
5) Although PRA and plasma ATase activity in human chronic renal failure ranged widely, an increasing tendency was seen as compared with control subjects. Marked increase in PRA was seen in 13.9% and marked increase in plasma ATase activity was seen in 19.4%.
6) PRA was significantly incresed after hemodialysis of human chronic renal failure but plasma ATase activity was unchanged.
7) A case of chronic renal failure with severe hypertension was presented, who became normotensive 10 days after bilateral nephrectomy. PRA was decreased gradually after bilateral nephrectomy and was undetectable after 48 hours. Plasma ATase activity showed a temporary decrease after bilateral nephrectomy but remained at the preoperative value thereafter. From the above results, the followings were concluded:
PRA and plasma ATase activity were showed an increasing tendency in human chronic renal failure. There were a few renin-dependent hypertensions in chronic renal failure. Change of plasma ATase activity was nonspecific and did not show any correlation with PRA or levels of blood pressure.

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For the purpose of investigating and the condition of catecholamines (CA) in renal failure, adrenaline (A) and noradrenaline (NA) levels in plasma and urine were determined by the trihydroxyindole method (a modified technique of Stern and Brody method). Plasma A and NA levels were observed in 18 dogs; in 6 of which the both ureters were ligated, in another 6 the both kidneys were removed and in the remaining 6 a sham operation was performed as a control group. Plasma A and NA levels were also observed in 51 human subjects; 3 were with acute renal failure, 17 with chronic renal failure, and as the control group, 14 normal subjects, 6 with pheochromocytoma and 11 with essential hypertension were observed. Urine A and NA levels were determined in 45 cases; 8 were with chronic renal failure, 13 with normal findings, 6 with pheochromocytoma and 18 with essential hypertension.
The results were as follow;
1) In dogs, plasma A and NA levels showed an increasing tendency after bilateral ureter ligitation or bilateral nephrectomy, but the changes were not significant.
2) In essential hypertension, A and NA levels in plasma and in urine were not different from those of normal subjects. On the other hand, in pheochromocytoma, plasma A and NA levels were elevated in the majority of cases and urine levels increased markely in almost all cases.
3) In acute renal failure, it was observed that plasma NA level was elevated in oliguric phase and plasma A and NA levels increased lightly in diuretic phase, however, final conclusion could not be drawn because of the small number of cases.
4) In chronic renal failure, plasma A and NA levels showed wide distribution as compared with the control groups and had the tendency of increase, although they did show such a marked increase as in pheochromocytoma.
5) Plasma A and NA levels had no differrence between arterial and venous bloods and had no significant correlation with each other in chronic renal failure.
6) There vvas no significant correlation between plasma A and NA levels and blood pressure in chronic renal failure.
7) Plasma A and NA levels in chronic renal failure seemed to increase in severe or insufficiently dialysed cases.
8) Plasma A and NA levels decreased significantly by hemodialysis. The degree of decrease was marked in NA.
9) Urine A and NA levels were significantly low in chronic renal failure as compared with the control groups.
The results reveal that plasma CA levels in renal failure, especially in chronic one, have a tendency of increase in general, although the distribution is considerably wide, and indicate that the increase may be mainly due to the marked decrease of urinary excretion of CA. The results also indicate that plasma CA does not increase whe nhemodialysis is performed suitably, because CA is easily removed by hemod-dialysis, and that plasma CA has little relation to the development of hypertension in renal failure.

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Cystoscopy is the most important method in the diagnosis of bladder cancers. However, some cases can not be diagnosed by cystoscopy. We had six cases of the socalled silent bladder cancer, in which the surface of the bladder was nearly normal or with appearance of chronic inflammation, and the sign of tumours could not be detected by the cystoscopical examination. Therefore, we report our experience and give some considerations on the diagnosis and treatment of such cases.
Of all six cases, five cases had received the medical treatment in a certain hospital from 3 months to 3 years under diagnosis of chronic cystitis, cystitis tuberculosa or prostate hypertrophy. In those six cases, no marked abnormality was observed by IVP, cystogram, and arteriogram. And no tumour was found even by bimanual palpation nnder lumbar anesthesia. The cystoscopical diagnosis was not available for these cases. The highly malignant cancer cells were detected by the cytological examination of pumping method and then biopsy gave the correct diagnosis of the high grade transitional cell cancer. Any tumour was not found macroscroscopically on the surface of the bladder after radical cystectomy. But the histological study on the preparations of whole area of the cystectomized bladders revealed that considerable part of the mucosa was invaded by cancer and tumour embolisms occured in the blood and lymph vessels. Cancer cells infiltrated not so far, the stage being mostly stage 0 or stage A. On the other hand, the lymph node metastases were often observed around the bladder. We studied its chromosomal patterns in four cases and found abnormal chromosomes in all cases.
Usually, the diagnosis of bladder cancer is relied on the cystoscope, and the therapeutic indication is dicided on the basis of the infiltration. However, as the matter of fact, this criteria does not apply to some cases of bllader cancer; for these cases, cytological examination and biopsy are indispensable.
For these cases, even if they are low stage cancers, the palliative operations are improper, and the radical cystectomy combined with strong chemotherapy or radiotherapy are required.

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To clarify the physiological innervation of the lower lumbar spinal cord to the urinary bladder of the dog, a selective electro-stimulation (monophasic, 5V, 2msec, 10Hz, 5sec) of the ventral rami of the L_5.6.7 lumbar nerves was performed, and the change of the intravesical pressure, as a response of the bladder to the stimulus, was observed with the isometric cystometry technique.
In addition, various nervous pathways to the urinary bladder from the lower spinal cord, including the ventral rami of the L_5.6.7 lumbar nerves, were cut off systematically, and its effects on the vesical response were examined.
The results obtained were as follows:
1. The selective electro-stimulation of each of the ventral rami of the L_5.6.7 lumbar nerves evoked vesical contraction response.
2 a The selective centrifugal electro-stimulation of the ventral rami of the L_5.6.7 lumbar nerves, which had been severed proximally produced no vesical response. But the selective centripetal electrostimulation of the ventral rami of the L_5.6.7 lumbar nerves, which had been cut distally, caused vesical contraction response.
3. The vesical contraction response induced by the unilateral centripetal electro-stimulation of each ventral ramus of the distally cut L_5.6.7 lumbar nerves was remained after the additional and individual or successive section of the nervous pathways, e. g., the transection of the spinal cord at the level of Th_10-11, cutting of the contralateral ventral rami of the L_5.6.7 lumbar nerves, bilateral cutting of the hypogastric nerve, bilateral L₇ ganglionectomy of the sympathetic trunk, and bilateral cutting of the pudendal nerve.
4. The vesical contraction response, whose appearance was confirmed in advance after cutting various nerves as described above, disappeared after the additional transection of the spinal cord at the level of L₇-S₁, or bilateral cutting of the pelvic nerve.
5. From the results obtained above, it was assumed that the lower half of the lumbar spinal cord of the dog posess a certain functional mechanism, which receives the centripetal stimuli via the ventral rami of the lower lumbar spinal nerves, mediates it to the efferent system in the sacral cord via some intraspinal descending systems, and makes the urinary bladder contract via the pelvic nerve.

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Clinical statistics of the male genital tuberculosis during the past 10 years (1961-1970) in Japan were studied.
The incidence of genital tuberculosis increased significantly since 1922, reached its peak (6.6% of the outpatients) after World War II (1946-1949). After that it tended to decrease gradually and recently it is only 0.4%. The decrease of incidence of the disease is thought to be related to the chemotherapy.
The diseased side was in 72.7% unilaterally in the epididymis and in 47.1% bilaterally in the seminal vesicles. More than 2 genital organs were invaded in 24.4%.
Combination of operation and chemotherapy were mostly given for epididymis and chemotherapy played the chief role in the treatment of other cases. As chemotherapy, the 3 combination therapy of SM, PAS and INAH was done in most cases. The administration periods ranged about 6 months to 2 years when chemotherapy was combined with operation and 1 to 2 years or more when chemotherapy was given alone.
The follow up studies were made on 139 patients in the Gifu and Nagasaki University Hospitals. The combination of operation and chemotherapy showed the best result, however there was no significant difference between the operative and non-operative groups. The opposite side of epididymis was invaded in 16.0-18.4% after the treatment.
Sixty to 70% of the patients had normal sexual function, 26 to 35% had decreased sexual potency, about 8% were impotent and 27.6% had no ejaculation. The severity of sexual dysfunction was high in patients with tuberculous lesions in more than 2 genital organs. Even in the unilateral cases the wives of the patients never conceived in 50.9-69%.
With the progress of chemotherapy the prognosis in general condition of the patient with genital tuberculosis has been markedly improved, however some problems of sexual function still remain unsolved. It is important to protect the opposite side of the genital organ from invasion of disease by removing the diseased epididymis earlier and to cure remaining changes in the seminal tract by further long term chemotherapy.

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The case: age: 31. Male. Unmarried. About 3 months before, this patient noticed pain in left testis. As the pain became worse in the last few days, he visited the hospital. The left posterior epididymis was swollen to the size of the tip of a thumb. Stiffness and tenderness were slight. Left epididymectomy was done under the diagnosis of tuberculous epididymitis.
The surface of the tumor was flat and smooth. It was yellowish in color, and ball shaped and hard. The section was gray-yellowish white in color and was like meat. However, no direct connection with epididymis was evident.
Histologically, the cell border of the tumor was indistinct. The cell was generally cubic or multilateral in shape and the cytoplasma was slightly stained with eosin. Epitheloid cells with bright nuclei were surrounded by connective tissue in funicular, adenomatous, or indefinite groups, and were accompanied by several stages of vacuolations including even signet-ring-like cells. The vacuolated cells looked like lymphangioma. In the marginal part of them, layers of smooth muscle fibers and spreading type or clearly bordered round-shaped groups of lymphoid cells were seen. One peculiar feature of this case was unusual positive fat coloration. However, it was not seen in vacuoles.
Including this case, 35 cases in Japan were discussed. The side of the tumor was on the left in 21 cases and the right in 11 cases. The side was not reported in the remaining 3 cases. The location of the tumor was in the tail part in 20 cases, in the cephalic part in 9 cases, and in the spermatic cord in 1 case. The location was not reported in the remaining 5 cases. When they were classified by age; 30s was the top with 18 cases, followed by 40s 7 with cases and then 50s with 5 cases.
The histogenesis is still in dispute. However, two popular theories are that of mesothelioma and that of Mueller's tube origin. The author is for the latter theory from the similarity to the cross section of 22mm embryos and the appendix of the testis, which is generally believed to be originated from the Muller tube. However, there is still uncertainty concerning the histology of the cells of this tumor. Another findings which made me support the theory of Mueller's origin are adenomatous features of the cells and a chain appearance in the appendix of testis.
Those that are reported as multiple adenomatoid tumors, malignant adenomatoid tumor or localized infiltration usually show multiple, papillary, soft and uncovered tumors on the serous membrane of hydrocele and should be differentiated from those which are single, round, and hard, being covered by a membrane. They all should be called mesothelioma. And it is not adequate to consider the disseminated sites as metastais and filtration which mean malignant changes.

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