Purpose: Patients with chronic renal failure and/or under-going chronic hemodialysis therapy are subjected to a number of well known cardiovascular risk factors. Although they are the leading causes of death, the reasen is not clear. Extensive tissue deposit of oxalate crystals is a complication in chronic renal failure and chronic hemodialysis. But little attetion has been paid to this secondary oxalosis, especially in myocardium and cardiac conduction system, which occasionally causes sudden death. The purpose of the present study is to evaluate the relationship among the severity of oxalate crystal deposition in renal and myocardial tissue, the state of the renal disease, and the duration and frequency of hemodialysis.
Material & Method: The twenty-eight autopsied materials were as follows: (A) Underlying disease. —Primary hyper- oxaluria (1 case), Nephrotic type nephritis (1 case), Shönlein-Henoch (1 case), Nephrosclerosis (1 case), Renal stone (1 case), Heart failure (1 case), Pyelonephritis (4 cases), Chronic glomerulonephritis (17 cases), Unknown causes (4 cases). (B) Ten of the twenty-eight cases were performed peritoneal dialysis. The calcium oxalate crystals in tissue was detected by the following technique. It was identified as light yellow-brown crystals in hematoxiline-eosin sections. They showed characteristic forms of rossetteshaped, ellipsoidal and prismatic forms. Under polarised or semi-polarised light, the crystals had double refraction. In case of gross crystals, they were ground into powder and confirmed histologically.
Results: Fifteen of the eighty patients (54%) had calcium oxalate crystal deposition in renal tissue. Six of the twenty-eight patients (21% had calcium oxalate crystal deposition in myocardial tissue. Some of them were found in the atrioventricular node and His bundle. These cases were more or less associated with necrosis and fibrosis in the myocardial and/or conduction system. One patient showed sino-atrial block, hypercalcemia and other severe pattern. Although, he had soon recovered clinically to a good condition by peritoneal dialysis, died suddenly. The autopsy finding showed a great number of calcium oxalate crystals in the cardiac muscle and conduction system. Other two cases were maintained well by peritoneal dialysis, but similarly died suddenly.
Comment: The incidence of renal and cardiac deposition of calcium oxalate are much larger than initial expectation. The incidence was similar to that in the report of Fayemi O (1979). Cardiac lesions in secondary oxalosis with focal necrosis, difuse fibrosis, congestive heart failure and conduction defects have also been described. We emphasise that the calcium oxalate deposition of the heart muscle and conduction system sometimes induces sudden cardiac death, despite clinically good states.

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Based on the theory proposed by Phillips that there is a potential effect between radiation and bleomycin (abbreviated: BLM), we have studied the carcinostatic effect on bladder carcinoma of BLM which is routinely used in the treatment of squamous cell carcinoma and which is said to be effective in inhibiting the recovery of cancer cells from damage by radiation.
The patients were 51 to 81 years of age, 64 on the average, and comprised a series of 14 cases, 12 males, including six with fresh carcinomas (50.0%) and six with recurrent ones (50.0%) treated with other carcinostatics or by operation (TUR-Bt), and two females, both with fresh bladder carcinoma. The all cases were transitional cell carcinomas, graded I to IV. Following the therapeutic method planned by us, 60mg of BLM in 40 to 60ml of sterile distilled water was instilled into the bladder cavity, and the focus was irradiated with ⁶⁰Co to a focal dose of 100 to 150 rad 30 minutes later, and injected intramuscularly 2mg of BLM 30 minutes after the radiation; and this pattern of treatment was repeated once or three times a week, ten times in total. The combination therapy of BLM and radiation was effective in five cases (35.7%). These cases were grade I to III and fresh ones. Two tumors (18.9%) completely disappeared on this combination therapy. The side effect was only irritable bladder symptom. Pulmonary fibrosis, pulmonary and hepatic dysfunctions and abnormal blood biochemical findings were not seen.
There are a variety of carcinostatic agents for treatment of bladder carcinoma, but BLM is only one having an inhibitory effect on the recovery of cancer cells from damage by radiation. It is the drug which should be classified into a special category for combined use with radiation.

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Serum β-subunit of human chorionic gonadtropin (β-HCG) and alpha fetoprotein (AFP) levels were determined serially by a double antibody radioimmunoassay method on 3 patients with non seminomatous germinal cell tumors of the testis before and after operation. Preoperative serum β₁-pregnancy specific glycoprotein (SP₁) levels were determined by the single radial immunodiffusion method.
Before and after operation serum levels of β-HCG and AFP were changed in good correlation with clinical course, although serum (SP₁) was not detected in all patients.
Tissue specimens of testicular tumors and metastatic tumors to the retroperitoneal lymph nodes were studied for the cellular localization of β-HCG, SP₁ and AFP by peroxidase antiperoxidase method on formalin fixed paraffin embedded tissue, following the demonstration of β-HCG and SP₁ within syncytiotrophoblastic giant cells, giant cells interspersed with embryonal carcinoma and a part of epithelial cells lining cyst.
AFP was demonstrated within endodermal sinus tumor cells, a part of embryonal cells within embryonal carcinoma and epithelial cells lining cyst.
The presence of β-HCG, SP₁ and AFP in these tumor tissues were correlated with their preoperative serum marker levels.

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We have studied the cell-mediated immune status in renal cancer patients and the changes in the status produced by surgery and chemotherapy. This has been done by measuring both in vivo parameters (PPD skin test, lymphocyte counts) and in vitro parameters (blastogenic response of peripheral lymphocyte to phytohemagglutinin and concanavalin A).
Analysis of 32 renal cancer patients who did not receive treatment revealed a range of blastogenic responce whose average was the same as healthy controls. If these patients were divided into three groups according to tumor growth pattern i. e. slow type, intermediate type, and rapid type, differences in relative immuno-impairment could be detected among the various groups. The lymphocyte blastogenesis reactions in the slow type group were lower than control, but their PPD skin tests were positive in almost all cases. On the other hand, the PPD skin test in the rapid type group revealed negative or false positive results. The blastogenesis reactions in this group were, however, higher than controls.
Trans-peritoneal radical nephrectomy did not induce dramatic changes in the immune parameters of these patients. On the other hand, systemic chemotherapy using either Adriamycin, CCNU or MFC therapy with OK-432 induced a suppression of blastogenic reactions. Such suppression, however, was not demonstrated by the use of FT-207 with OK-432.

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In mongrel male dogs the vesical contraction reflex (urethrovesical reflex, UVR) occurred when the urethra was distended with an inflatable catheter. As we have already reported, the “UVR” is accelerated after section of the hypogastric nerve. This shows that the sympathetic nerve may play. an important role not only in accumulation of urine in the bladder but also in facilitation of urination. In the present study, further neurophysiological and neuropharmacological experiments especially with adrenergic drugs were performed and the following results were obtained.
1) The “UVR” occurred not only when the balloon was inflated but also deflated in the urethra. However, the vesical contraction was stronger at the deflation of the balloon than at the inflation. This result may suggest that the “UVR” occurs more strongly when the urinary force is weakened and the pelvic floor musculature is relaxed rather than when the urine is passing through the urethra.
2) Regarding the effects of adrenergic drugs to the “UVR”, α-adrenergic drugs had no demonstrable effect on the “UVR”, but β-stimulant (isoproterenol) had a suppressive effect and β-blocker (propranolol) had an accelerating effect on the “UVR”. These results suggest that the sympathetic nervous system affects the “UVR” via the β-receptors with the sympathetic motor innervation.
3) The “UVR” is considered to have a certain role in the cause of enuresis and urinaty incontinence. Imipramine is well known for its beneficial effects in the treatment of enuresis and urinary incontinence, although its exact mechanism of action is unknown. The fact that the “UVR” was suppressed by imipramine appears to give experimental support to the clinical usefulness of imipramine. It seems unlikely that the effect of imipramine results primarily in augmentation of the muscular tone of the involuntary urethral sphincter by sensitizing the α-receptors with sympathetic motor innervation.
4) Depolarizing muscle relaxant, suxamethonium had no effect on the “UVR”. This may suggest that suxamethonium does not influence either initiation or continuation of urination.

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Kidneys in rats were made hydr onephrotic by unilateral ligation of the ureters close to the bladder. Succinate cytochrome C reductase (SCR) and lactic dehydrogenase (LDH) were measured in the hydronephrotic and the contralateral kidneys.
Changes of weight and gross appearance of the kidneys were observed and histological studies were made on hydronephrotic kidneys.
1) SCR and LDH in the kidneys with ureteral obstruction for 3 days were significantly lower than those of control group. At this time of ureteral obstruction, the renal pelvis is slightly dilated but atrophy of the renal parenchyma has not yet occurred judging from the change of dry weight ratio. It seems that there is a definite metabolic alteration in the kidney in the early stage of ureteral obstruction.
2) SCR and LDH progressively decreased in activity until 3 weeks of ureteral obstruction with no significant change in activity thereafter. SCR and LDH in the contralateral kidneys showed no change from those of control group up to 7 weeks of ureteral obstruction.
3) Histologically, renal tubular epithelium was destroyed in some areas in kidneys with ureteral obstruction of more than 2 weeks and interstitial connective tissue became rather prominent. Glomeruli were preserved relatively well even in kidneys with ureteral obstruction of long duration (6 or 7 weeks).
Ureteral obstruction was released by means of ureteroneocystostomy. Contralateral nephrectomy was performed 4 weeks after ureterocystoneostomy and the remaining kidney was also removed one week later. Serum creatinine was measured 48 hours and one week after contralateral nephrectomy.
Intravenous pyelography (IVP) was performed 4 weeks after ureteroneocystostomy and just prior to contralateral nephrectomy to check the patency of ureteroneocystostomy. SCR and LDH were measured in the removed kidneys whose ureteral obstruction had been released 5 weeks before. Histological studies were also made on these kidneys.
4) The kidneys with ureteral obstruction of more than 4 weeks' duration did not recover sufficiently to sustain life after release of ureteral obstruction.
5) Renal function after release of ureteral obstruction roughly was correlated with renal SCR but not with LDH.
6) Histologically, the kidneys with ureteral obstruction of short duration remained almost normal after release of ureteral obstruction. However, in the kidneys with ureteral obstruction of long duration (3 or 4 weeks), destroyed and well preserved areas were noted intermingled after release of ureteral obstruction.
7) The kidneys whose ureteral obstruction had been released by means of ureteroneocystostomy became visualized on IVP. This shows that release of ureteral obstruction using ureteroneosystostomy is technically successful. The longer the duration of ureteral obstruction prior to ureteroneocystostomy, the larger the renal pelvis and the poorer the excretion of contrast medium.
8) In this experimental model, there was no difference in enzyme activities between kidneys with ureteral obstruction for 3 weeks (reversibly damaged) and those with ureteral obstruction of 4 weeks
(irreversibly damaged) before release of obstruction. Histological distinction also could not be made between these two groups before release of obstruction.

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With 191 randomly selected patients, of which 56 cases were histologically defined as having carcinoma of the prostate, the diagnostic usefulness of results obtained from measurement of acid phosphatase levels in serum by enzymatic assay of King-Armstrong (TAP and PAP) and radioimmunoassay of Mallincrodt RIA Quant-P. A. P, test (RIA-PAP) were compared and the following results were obtained.
1) With control cases, the upper limit of serum RIA-PAP levels was 2.0ng/ml. This level was increased along with the advance of the age and the upper limit of normality in the group more than 70 years of age was 2.2.ng/ml.
2) In cases with carcinoma of the prostate, the mean serum levels of all three RIA-PAP, TAP and PAP were statistically significantly higher than the levels obtained in the controls and patients with benign hyperplasia of the prostate.
3) With the patients having stage A-B carcinoma, the enzymatic assay was abnormally higher in 22per cent of them. With RIA-PAP, on the other hand, abnormal elevation was found in 33 per cent of them. However, a diagnostic accuracy of 56 per cent was obtained if both studies were performed simultaneously. The author has concluded that at present simultaneous studies of PAP and RIA-PAP are more favorable for detecting early carcinoma of the prostate.
4) In the cases with benign hyperplasia and carcinoma of the prostate, RIA-PAP levels were highly significantly correlated with TAP and PAP levels.

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Ligation of the rat (Wistar) ureter was done for 1, 2, 3 days and 1 week in order to produce hydronephroais. After nephrectomy, papilla, fornix, brown pelvis and white pelvis were fixed by 2% glutaraldehyde solution (Millonig buffer pH 7.2). Then each specimen was dehydrated through a graded ethanol, which was replaced in isoamyl acetate. They were critical point dried, coated with gold and observed by scanning electron microscope.
The results of the observation were as follows.
1) Rats have unipapilla, and their pelvis could be separated macroscopically into those with brown and those with white pelvis.
2) Enlargement of the orifice of the papillary duct began to be observed after 24-hour hydronephrosis, and became more evident as time passed.
3) Increase of microvilli on the papillary epithelium was observed as the hydronephrosis advanced. In 1-week hydronephrosis, fusing of microvilli was observed.
4) From the brown pelvis of 24-hour hydronephrosis rat, epithelial waving was observed, which suggested a tubular structure formed under the mucosa.
5) On the cell surface of the brown pelvis, microridge concentration toward the center of the cell was observed in a reticular and radial formation in accordance with the advance of hydronephrosis, and a microcrater was observed in the center.
6) On the cell surface of white pelvis were seen rippling folds focussing on the center of the cell, forming a microcrater as if it were a volcano.
7) There was no tendency to separation or scaling-off of cells, nor was forniceal rupture observed.
It was concluded that the urinary absorption in hydronephrotic rats occurs mainly through pyelotubular backflow.

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Host defense mechanisms on pyelonephritis were experimentally investigated in rats. In vitro phagocytosis of proteus mirabilis (Pm) by normal and immune rat peritoneal macrophages was evaluated under various conditions. Serum bactericidal activity against Pm was also studied. Retrograde pyelonephritis was induced in rats by transurethral inoculation of Pm into the bladder. The rats were sacrificed by cardiac puncture 7 days after the inoculation. The serum was recovered and macrop hage monolayers were performed from peritoneal exudate cells which were harvested with intraperitoneal injection of 0.1% glycogen. The phagocytic studies were performed with the macrophages monolayers in the presence or absence of 10% unheated or heated rat serum. The residual viable bacteria in culture fluids were calculated by the agar plate dilution method at interval times within 6 hours.
The results obtained were as follows:
1) No bactericidal activity of heat-inactivated normal and immune serum was detected against Pm. It is assumed that serum bactericidal activity against Pm was mostly dependent upon heat-labile factor.
2) It was shown that heat-labile factor promotes active phagocytosis of Pm by rat peritoneal macrophages, but that by heat-inactivated serum the phagocytosis was much decreased. The phagocytic activity of both normal and immune macrophages was significantly increased in the presence of immune serum when compared to normal serum.
3) No statistical difference between the phagocytic activity of normal and immune macrophages was detected in the presence of unheated serum, but immune macrophages were more phagocytic than normal macrophages after 6 hours of incubation in the presence of heat-inactivated serum. This enhanced phagocytosis of immune macrophages implies a role for activated macrophages resistant to Pm.
It is assumed that cell-mediated immunity might be part of the host defense mechanisms to Pm retrograde pyelonephritis in rats.

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In an earlier paper of this series, it is shown that calcitonin influences on the calcium metabolism of patients with urolithiasis, especially hypercalciuric patients. However little work has been done to evaluate effects of calcitonin on the urinary excretion of electrolytes and renal calcitonin metabolism.
Effect of calcitonin was studied in patients with primary hyperparathyroidism, hypercalcemic malignant tumors, and urinary calculi. We further investigated the calcitonin metabolism in intact and parathyroidectomized (PTX) rats.
Forty or eighty MR Cunits of eel calcitonin which has the highest biological activity, was injected into the patients intramuscularly every morning. Every two-hour urine samples were collected after injection, and blood was collected three hours after injections.
The results were as follows:
1) Patients with malignant tumors had a serum calcitonin level significantly higher than those with hyperparathyroidism (209.8±41.2pg/ml, 63.2±38.8pg/ml respectively, p<0.001). However, both parathyroid hormone and urinary cyclic AMP levels were significantly lower in the former than the latter. (parathyroid hormone 0.315±0.260ng/ml, 6.10±7.63ng/ml respectively, p<0.05), (Urinary cyclic AMP 6.0±5.0μmoles/g.cr, 12.4±6.4μmoles/g.cr p<0.05).
2) Single injections of calcitonin induced a highly significant increase of the urinary excretion of calcium, phosphate, magnesium, and sodium after two hours. It returned to the previous level after eight hours. The preadministration serum calcium levels were directly proportional to the degrees of the decreases after administration.
3) The injection for several days caused a decrease of urinary calcium excretion in 8 of 11 cases, but minimal or no changes were observed in urinary phosphate excretion. There was no difference between malignant tumors and hyperparathyroidism.
4) Administration of eel calcitonin showed that there was minimal or no changes in serum calcitonin levels. Single injections of calcitonin caused moderate increases of parathyroid hormone in some cases, but no changes in the other cases.
5) Single injections of calcitonin resulted in a marked increase of urinary cyclic AMP excretion in patients with hyperparathyroidism, and there were moderate increase in those with malignant tumors. The cause of the increase remains unexplained, whether it is attributable to the calcitonin direct action or the parathyroid action followed by serum calcium reduction.
The following experiment was made to investigate this problem. Eel calcitonin was administered into intact and PTX rats, weighing about four hundred grams, intraperitoneally at a dose of 0.3MR-Cunits/100g body weight. Sample collection methods in this study was the same as that described in human beings. In this experiment slight to moderate increases in urinary cyclic AMP excretion was noted in intact rats as well as PTX rats. Based on this finding it is logical to believe that the increase is due to the calcitonin direct action, i. e, cyclic AMP may be the second messenger of calcitonin.
6) Injections of calcitonin for several days resulted in a marked reduction of urinary calcium excretion in four of five hypercalciuric patients (more than 200mg/day). But there was minimal or no changes in all normocalciuric patients. These results suggest that calcitonin is useful to investigate calcium metabolism in urolithiasis as well as to treat patients with urinary calculi.

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