The clinical effects of the treatment with rice-bran in calcium stone formers with idiopathic hypercalciuria were studied, and the mechanism of the effects was investigated.
The results were as follows:
1) Thirty-one patients with idiopathic hypercalciuria were treated with 10g defactted rice-bran per day. 22 of them (70.9%) developed a significant reduction in urinary calcium excretion (mean reduction rate: 21.2%) after 4 weeks.
Seventeen of 19 patients (89.5%) reduced their urinary calcium excretion (mean-reduction rate: 29.8%) after treatment with 20g of defatted rice-bran per day.
Although, reductions in urinary calcium excretion were observed in both groups of 10 g and 20g administration, non-responsive patients were more frequent in the group of 10g administration.
2) There were no change in urinary phosphate, serum calcium and phosphate during treatment.
3) Of thirteen patients treated with rice-bran pharm. (20g/day), culture products of defatted rice-bran, 10 developed a reduction in urinary calcium excretion (mean reduction rate: 22.7%). On the other hand, 8 patients, on administration of wheat-bran pharm., could not reduce their urinary calcium significantly.
4) In 6 patients, urinary calcium excretion rose after rice-bran treatment had been stopped for 4 weeks. It was considered that urinary calcium reduction was due to the effect of rice-bran itself.
5) In 7 patients, urinary calcium increased after defatted rice-bran had been replaced with dephytinized one for 4 weeks. The results suggested that the major effect of rice-bran for urinary calcium might be due to phytin.
6) In 4 patients, ⁴⁷Ca absorption tests were performed at pretreatment and during treatment with defatted rice-bran. Reduction of intestinal calcium absorption (5-10%) was observed in all of them. The effects of rice-bran on calcium excretion is probably due to the combination of phytin with calcium in the intestine to form insoluble and non-absorbable calcium phytate.
7) No patients had any severe side-effects of rice-bran therapy. Rice-bran seems to be a kind of natural food without unwanted side-effect and effective in reducing urinary calcium excretion with idiopathic hypercalciuria. Therefore, rice-bran therapy should be considered an ideal therapeutic agent for calcium stone formers with idiopathic hypercalciuria.

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Binding of calcium by rice-bran was investigated in vitro, for the purpose of studying the mechanism of rice-bran binding to dietary calcium in the intestines.
The following results were obtained:
1) Much of the calcium was bound by 0.1% Na-phytate (Sigma Co.). When phytin from rice-bran (0.1%), defatted rice-bran (1%) and rice-bran pharmacopoeia (1%) were dissolved with 0.1 N HCl, similar effects wre observed.
2) Phytin and defatted rice-bran were poorly soluble in neutral solutions, and high abilities to bind calcium were obtained on dissolving with 0.1 N HCl or human gastric juice.
3) Rice-bran pharm. showed a stable ability to bind calcium both in neutral and acid solutions. Phytin in rice-bran might be denatured to a highly soluble phytate by cultivation of defatted rice-bran.
4) The quantity of calcium binding of rice-bran pharm. was far greater than that of wheat-bran pharm. This has been confirmed in the reported clinical results.
5) The binding of calcium by phytic acid was increased in a weak alkaline solution.
6) The effects of rice-bran pharm. on calcium was depended on its concentration.
7) Cellulose from rice-bran did not show any abilities to bind calcium, and dephytinized rice-bran showed less than defatted rice-bran. The results suggested that phytin in rice-bran was the major factor of calcium binding.
8) Rice-bran pharm., culture products of defatted rice-bran, should be a suitable agent for rice-bran therapy in this experiment.

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The purpose of this study is to assess the biological effects of rice-bran or phytin. Metabolic balance studies of calcium were carried out in male rats during treatment with rice-bran, phytin and Na-phytate, and evaluated the influence of high and low dietary calcium intakes on their effects.
The following results were obtained:
1) When rats were fed with the high calcium diet, urinary calcium excretion was significantly reduced by treatment with rice-bran and phytin. There was no significant difference in the effect between rice-bran and phytin.
2) In the low calcium diet, rice-bran and phytin had no significant effect on urinary calcium excretion. A marked difference in the reduction of urinary calcium was observed between the high calcium diet and the low calcium diet.
3) Similar effects on urinary calcium excretion were obtained on administration of Na-phytate (200mg/day).
4) On the high calcium diet, rice-bran and phytin significantly reduced the absorption of calcium in the intestines. In contrast, its reduction was slight on the low calcium diet. These findings suggest that utilization of phytate phosphorus probably enhances on the low calcium diet, and diminishes on the high calcium diet.
5) The whole group of this study had no significant effects on serum calcium and parathyroid hormone. Growth rate and calcium contents in the femur were affected by rice-bran and phytin administration.
6) Rice-bran treatment was suggested to be more effective with high dietary calcium intake. This result should be taken into consideration in its clinical use.

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The vascular pattern of capillaries and small vessels in normal urinary bladder of rats and humans and in bladder tumor of humans was investigated by scanning electron microscopy of the vascular resin casts.
The vascular changes during bladder contraction and distension were studied using rat bladder and were compared with normal human bladder in contracted condition. In distended bladder of rat, capillaries under the vesical epithelium were arranged as a spider-like network consisting of irregular polygons in one plane with the luminal surface. Several capillary polygons were connected to the deeper vessels but the connecting vessels were loose. In contraction, the subepithelial capillaries were tortuous and helical, and the deeper vessels were also tortuous.
The vascular pattern of human subepithelial capillaries was very similar to that of rats. Some capillaries, however, did not form a complete polygonal ring and some crossed over each other. Connecting vessels in muscle layer were denser in humans.
In bladder tumor, superficial capillaries were irregularly tortuous and helical, and did not form a polygonal network. Vascular pattern in tumors showed a blind ending of capillaries, dilated tortuous veins, bundled dilated veins and pampiniformis plexus-like veins.

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It has been generally accepted that natural killer (NK) cells are responsible not only for various tumor cells in vitro, but also for the possible role in the resistance against growth of tumor cells in vivo.
This study was designed to demonstrate the human NK cell activity against cell lines dervied from malignant tumors of the urinary tract, and the effects of human interferon-β (IFN) on augmentation of NK cell activity.
Peripheral blood lymphocytes (PBL) from the buffy coat, obtained from healthy male volunteers, were separated by centrifugation on a Ficoll-Conray density gradient. IFN-treated and non-treated PBL were used as the effector cells. Different cell lines derived from carcinoma of the prostate and kindney were utilized as monolayer cells for immunoadsorption and target cells for a short-term ⁵¹Cr-release assay. K562 cells, well known for their high susceptibility to NK cell-mediated cytotoxicity, were used as the control. IFN-stimulated PBL were depleted of target-binding NK cells on various monolayrs and aliquots of nonaldherent PBL were assayed for their residual NK cell activity. The finally recoverd non-adherent PBL, after the third immunoadsorption, were cultured with IFN to examine the possibility of recruitment of NK cell activity.
The present study demonstrates the following: 5 different anchorage dependent cell lines used in this study were resistant to natural cytotoxicity; preincubation of monocyte-depleated PBL with IFN significantly increased NK cell activity against target cels as well as against K562 cells; and after almost complete loss of NK cell activity by immunoadsorption, appreciable NK cell activity was restored by the subsequent incubation with IFN. This result suggests that IFN promotes the differentiation of human pre-NK cells (immature NK cells) to the active NK cells (mature NK cells) and that there are several stages in the course of the maturation of NK cells.

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Studies on the human natural killer (NK) cell-mediated cytotoxicity have attracted much attention in cancer research because of the important potential role of NK cells in immuno-survillance against various tumor cells in vivo. However, information on the specificity of NK cell activity and the mechanism of binding of NK cells to the target structure (TS) of tumor cells is relatively meagre.
In this study, the specificity of the human NK cell activity against various tumor cells was evaluated. K562 cells well known for their susceptibility to NK cell-mediated cytotoxicity and other 5 tumor cells derived from carcinoma of the kidney and the prostate were used as target cell (TC). Monocyte-depleted human peripheral blood lymphocytes (PBL) were preincubated with human interferin-β (IFN) for 12hrs, which were used as effector cell (EC) in cold target inhibition assay and sequential immunoadsorption method. Sequential immunoadsorption method was designed for the complete depletion of NK cells capable of conjugating with monolayer cells. After EC were depleted of their NK cell activity on various monolayer cells, aliquots of nonadherent PBL were assayed for their residual NK cell activity against various TC. NK cell activity was determined in a 4h ⁵¹Cr release assay.
The present study demonstrates the following: both of K562 and other 5 tumor cells express their common TS which is recognized by IFN-stimulated PBL: the results of cold target inhibition assay indicate that K562 and Caki-1 cells each exhibit a characteristic set of TS: human NK cells are polyclonal, some of them capable of recognizing the characteristic TS and others having a more broad specificity: the specificity of the human NK cell activity seems to vary individually, depending upon the array of various NK cell subpopulations.

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In 25 patients with prostatic cancer confirmed histologically, 24 patients had bone metastasis on the whole body bone scintigraphy. The extent of bone metastasis was estimated quantitatively by the computerized digitizer. At the same time, the number of the metastatic lesions was counted. The correlations between the area of metastatic lesions on the ^99mTc-MDP bone scintigrams and ESR, LDH, total acid phosphatase, prostatic acid phosphatase, ALP and urinary hydroxyproline/creatinine levels were further investigated. The number of the metastatic lesions was also investigated with the same tumor markers. The results are as follows:
1) The extent of the metastatic lesions was showed more accurately by the area measured with the computerized digitalizer than by the number of metastatic lesions.
2) The correlation between the area of metastatic lesions and serum ALP levels was relatively high (γ=0.75). But almost all were within normal limits.
3) As for the relation between the area of the metastatic lesions and the urinary hydroxyproline/creatinine levels, the correlation was high (γ=0.78). And the hydroxyproline/creatinine levels were almost over the upper limit. Therefore, the urinary hydroxyproline/creatinine was considered as a good marker of the extent of bone metastasis.

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We measured urethral sphincter muscle pressure in several normal men and in more than 50 patients with benign prostatic hypertrophy, unstable bladder and spinal cord injury using MIKRO-TIP catheter pressure transducer (Miller Instrument, Inc.) for the study of urethral sphincter function.
Cystometrography and uroflowmetry combined with urethral sphincter electromyography, its muscle pressure, pressure change at maximum urethral pressure (UP_max) and anal sphincter tone pressure were performed. These recordings changed in parallel with urethral sphincter electromyogram in normal men. We consider that the recordings of the pressure change at UP_max and the anal sphincter tone pressure are not suitable for evaluation of the outfow resistance at the external urethral sphincter quantitatively based on the facts that the detrusor pressure is superimposed on the pressure change at UP_max during voiding, the anal sphincter tone pressure can not be expressed in absolute value and there is disparity between urethral and anal sphincter electromyograms in patients with neurogenic bladder dysfunction.
The values of intravesical opening pressure were almost equal to those of urethral sphincter muscle pressure in normal men. These values were different in patients with benign prostatic hypertrophy before operation but became equal after prostatectomy. These findings suggest that the muscle pressure shows the urethral pressure at the external urethral sphincter, although the microtransducer is placed in only the part of the urethral sphincter. The urethral sphincter muscle pressure ranged from 20 to 40cmH₂O during voiding in normal men and in patients with benign prostatic hypertrophy. The abdominal pressure appears to have influence on the sphincter muscle pressure. Therefore it seems appropriate to monitor the abdominal pressure in conjunction with the sphincter muscle pressure.
We feel that the recording of the urethral sphincter muscle pressure which changes in parallel with urethral sphincter electromyogram enables one to evaluate the outflow resistance at the external urethral sphincter quantitatively and it is especially useful to examine the patients with spinal cord injury who show abnormal function at the membranous urethra.

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An ultracytochemical study was performed on the epithelial cells of rat ventral prostate under various hormonal conditions. Adult rats of Wistar strain weighing about 200gm were used. The prostatic tissues were obtained from normal, castrated as well as castrated and androgen administrated rats.
Acid phosphatase (ACPase) and thiamine pyrophosphatase (TPPase) activities and horseradish peroxidase (HRP) labeled lectin binding sites were studied ultracytochemically in these specimens. The lectins used were concanavalin A (Con A), which bound to mannose-like sugars, and Ricinus Communis agglutinin (RCA), which bound to galactose-like sugars.
Normal prostatic epithelium was lined with tall columnar cells having well-developed endoplasmic reticulum and Golgi apparatuses. Castration induced an involution of epithelial cells. The cells reduced their sizes and organellae diminished both in number and in size. Restoration of morphology was apparent after testosterone injection in the castrated animals.
ACPase activities were localized in lysosomes and Golgi apparatuses. TPPase activities were found in Golgi cisternae and occasionally on microvilli. The localization of ACPase and TPPase activities were unchanged, although marked modulation of positive organellae were found in various hormonal conditions.
Con A bound to the cisternal surface of rough and smooth endoplasmic reticulum, nuclear envelope, Golgi membrane and multivesicular bodies. The outer surface of plasma membrane and basement membrane were also stained. RCA-HRP binding sites were Golgi membrane, multivesicular bodies, plasma membrane and basement membrane. The lectin binding sites on the cell membranes indicated the presence of respective specific sugars, e. g. Con A to mannose and RCA to galactose, and their differing distribution showed different surface properties of the membrane. The distribution pattern of each lectin binding sites was similar irrespective of cell proliferation or involution, although the amount of positive membrane varied according to the cell function. Therefore, the Con A and RCA staining can be used as a cytochemical marker of membranes in fixed tissue cells.
The lectin binding sites of the prostatic epithelial cells were revealed for the first time ultracytochemically. These markers of the membranes indicated the relationship between the cytoplasmic membranes and the plasma membrane. The present study showed the usefulness of phosphatase activities and lectin binding sites as cytochemical markers in the evaluation of cell structure in relation to its function.

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This is a sequel to our previous paper, entitled “Clinical study on uremic patients with ureteral obstruction secondary to malignant disease” (Jpn. J. Urol. Vol 73 (9)). This paper deals with serial observation of recovery from obstructive nephropathy after relief of ureteral obstruction, with special regard to post-obstructive diuresis (POD).
Forty-four patients were included in this study. They had uremia caused by ureteral obstruction secondary to malignant disease and their details were already described. Patients were classified into 2 groups, i. e. POD group and non-POD group. The former group consisted of patients who put out 4, 000ml. urine or more in a day after diversion, and included 9 patients (20%). One of the 9 patients put out maximum urine volume of 11.5 liter in a day. There was, however, no patient who was seemingly compatible with post-obstructive sodium losing nephropathy. Remaining 35 patients were included in the latter group who put out urine less than, 4.000ml. in a day. Then, recovery of the renal function after diversion was compared between the two groups.
In POD group, preoperative BUN and serum creatinine level were significantly higher than those in non-POD group (p<0.05), indicating that the osmotic load doubtlessly contributed to diuresis. However, needless to say this did not entirely explain it.
Despite the higher level of the initial BUN in POD group, faster decrement after diversion resulted in the BUN level similar to that of non-POD group by the 7th day and reached at a plateau. Namely, there was no difference between the two groups in days required until normal BUN level resumed after diversion. A similar trend was observed in the serum creatinine level as well.
Since urinary concentration of sodium after diversion was not different between the two groups, larger amount of sodium was excreted per day in POD group in proportion to larger volume of their daily urine output. This might have indicated that pre-operative total exchangeable body sodium contributed to the post-obstructive diuresis. In POD group, urinary concentration of creatinine was slightly lower than those of non-POD group for a short period after diversion. However, larger volume of urinary output in POD group exceeded this difference and consequently they excreted larger amount of creatinine per day.
Based on these findings, the presence or absence of the POD did not appear to reflect the reversibility of the obstructive nephropathy. On the other hand there seemed to be correlation between the time course of the FENa level after diversion and the reversibility of the affected kidney.
Finally we reported a case of restored renal function after 72 days following relief of ureteral obstruction causing anuria while on regular hemdialysis. This case could offer an answer to the question how long complete obstruction in the human kidney can be followed by recovery of renal function after release of obstruction.

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We carried out investigation on 166 patients with nonspecific epididymitis for the past five years with particular attention to their clinical course during the therapy with antimicrobial agents. Out of the 166 patients, 152 were out-patients and 14, hospitalized. All of the latter group were complicated with epididymitis.
Escherichia coli was predominantly isolated from urine of the out-patients while Pseudomonas aeruginosa was a major organism from that of the in-patients. Except a few chronic asymptomatic cases, all patients were treated with antimicrobial agents. The drugs most frequently used for the out-patients were antibiotics of the cephamycin series (47.7%), followed by penicillins (28.8%), sulfamethoxazole-trimethoprim (11.3%) and others. A more than 4-week observation of clinical course was made on 58 acute and 9 chronic cases after chemotherapy was instituted. Most of the acute cases showed in-provement in clinical symptoms within three weeks, but in one-third of the cases, scrotal induration persisted until after eight weeks. Particularly in those from whose urine no bacteria was isolated, the scrotal induration tended to persist longer than in others. Most chronic cases responded well to the antimicrobial treatment.
Eleven of the 14 in-patients who had no vasectomy had acute epididymitis after suprapubic prostatectomy. Ten of the 14 cases were on post-operative prophylactic chemotherapy when epididymitis occurred. Aminoglycosides were the most effective antibiotics for post-operative cases, and symptoms improved within 10 days in most cases, but one case needed orchiectomy one month later because of fistula formation and persisting pus discharge.

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Recently, R1881 receptor assays in prostatic cytosol have been developed as a one point assay because of small amount of available tissues. However, further investigations were needed for their technical accuracies. We have reported that total tissue DHT levels of prostate might be a useful indicator to predict the androgen dependency of prostatic cancer as well as receptor assays, although relations in DHT levels and NBS of R1881 receptor have not been examined. Therefore, we investigated these correlations in total tissue, cytosol and nuclear extract of BPH and normal prostate.
Cytosols and nuclear extracts were incubated with 0.25-8.0nM of ³H-R1881 (6 points) for 20 hours at 4°C, then unbound steroids were removed by 0.5% dextran coated charcoal. Specific binding was defined as the difference between total binding and nonspecific binding which was not displaced by the addition of 100 fold excess cold R1881. Binding studies were performed in the form of Scatchard plot analysis. DHT levels were measured by the radioimmunoassay reported previously.
DHT levels of total tissue were correlated well with those of cytosol and nuclear extract (r=0.582, 0.647 respectively). Furthermore, they were also correlated with NBS of nuclear extract (r=0.575) but not with NBS of cytosol. This problem should be attributed to that cytosolic R1881 receptor was not a pure androgen receptor because it contained progesterone binding protein. It was considered that cytosolic R1881 receptor assay should not be an appropriate method to determine the androgen dependency of prostatic tissues.
R1881 receptor of nuclear extract which was prepared with high ionic solution (TEDGK buffer) was proved to be a 3-4S receptor by sephacryl S-200 gel chromatography and steroid specificity studies revealed that nuclear receptor was not inhibited by progestins. Since close correlations were noted between DHT levels and NBS of R1881 receptor especially in nuclear extract (r=0.776), it was considered that the determination of total tissue DHT levels might possess clinical usefulness to clarify the androgen dependency of prostatic cancer. In addition, it has some merits, since it requries minimum amount of tissue and is stable for temperature compared to receptor assays.

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Physiologic experiments were carried out on decerebrated female dogs for the purpose of studying the urethral behaviors during mictural reflex. The bladder pressure was recorded simultaneously with internal and external urethral sphincter pressures, internal urethral sphincter movements in both longitudinal and transverse directions with strain gauge force transducers and external urethral sphincter electromyography. The rectal pressure was also recorded as a monitor of intraabdominal pressure.
1) In the decerebrated preparation, a powerfull detrusor contraction was elicited by both slow filling of bladder with water and inflation of an intravesical latex balloon.
2) The pressure in the internal sphincter dropped simultaneously with detrusor contraction elicited by balloon inflation. This pressure change was still observed after vesicourethral separation. However, the degree of the pressure drop was significantly reduced by disconnection of the bladder and urethra.
3) The pressure drop in the internal sphincter was not diminished after treatment with succinylcholine chloride and was not so influenced by administration of propranolol (1mg i. a.). But, it could hardly be distinguished after transection of hypogastric nerves or administration of phentolamine (1mg. i. a.).
4) The movements of internal sphincter did not have a definite tendency when measured by a pair of extraluminal strain gauge force transducers.
5) The pressure drop in the external sphicter occurred gradually before any rise in the bladder pressure, at the initiation of voiding. The electromyography of external urethral sphicter also demonstrated prevoiding decrease of the electroactivity. After treatment with succinylcholine chloride the prevoiding pressure drop could not be observed.
These results demonstrate that the pressure drop in the internal sphincter is depended on the nerve reflex and further reinforced by the vesicourethral muscle continuity. In addition, it is suggested that the nerve reflex is mediated by the hypogastric nerve and mainly controlled by the alpha-adrenergic receptor mechanism.

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Long term clinical course of renal cell carcinoma was analyzed for 82 patients who visited us from January 1965 to December 1972. The results were as follows:
1. The overall crude survival rate was 36.6% (30/82) at 5 years and 30.5% (25/82) at 10 years. For the 25 patients who survived 10 years the cumulative survival rate was 50.9% at 15 years.
2. Distant metastases were found in 52 of 82 patients (72%); of these 27% were found when first seen, 29% were noted at 4 years and 16% later than 5 years after nephrectomy. Metastases were still manifested in 4 patients at 10 years and 2 patients at 13 years after nephrectomy.
3. The majority of patients who survived for more than 10 years belonged to the group of low stage and low grade tumors; however low stage and low grade renal cell carcinoma was not a guarantee for a long survival. Crude survival rates for 36 patients with low stage and low grade carcinoma were 58% at 5 years and 50% at 10 years. Low grade and low stage are necessary but not sufficient conditions for long term survival.
From the above results the following can be concluded: (1) it is necessary to maintain long term follow-up. (2) To achieve more acceptable survival rates other treatment modalities such as postoperative prophylactic treatment should be considered as adjunct to surgery.

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In order to investigate the role of the renal kallikrein-kinin system, the urinary kallikrein excretion was determined by radioimmunoassay. In 34 normal controls, urinary kallikrein excretion was 107±15μg/day and never below 50μg/day. However, in the obstructive uropathy, the levels of urinary kallikerin excretion were very low. In 32 cases of obstructive uropathy without azotemia, urinary kallikrein was 57±6μg/day, and in 7 with azotemia it was 2.0±0.8μg/day. In polycystic kidney it was 71±29, and in medullary sponge kidney, 37±9μg/day.
In obstructive uropathy, significantly positive correlations were found between the urinary kallikrein excretion and 24hr Ccr. (r=0.61), or urinary concentration ability (r=0.70) and significantly negative correlations between the excretion and urinary β₂-microglobulin (r=-0.61) or serum β₂-microglobuin (r=-0.59). In obstructive uropathy with normal GFR level and with disturbed concentration ability, the urinary kallikrein excretion was low. From these results, it was suggested that, in obstructive uropathy, the urinary kallikrein excretion as well as the urinary concentration ability is disturbed earlier than GFR.
In hydronephrotic kidney of unilateral hydronephrosis, urinary kallikrein and kallikrein/GFR as well as GFR and urinary concentration ability were reduced markedly. In postobstructive diuresis, the urinary kallikrein level was not increased. However, the urinary level of prostaglandin E2 was increased markedly.

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The case was a 72-year-old male who had the chief complaint of a painless, gradually enlarging tumor in his left scrotum for the past 6 months. Radical orchiectomy was performed. Histologic examination of the tumor revealed a malignant fibrous histiocytoma of the scrotal wall. He received chemotherapy with Vincristine and Cyclophosphamide but no radiation therapy. He is living without metastasis during the 4 months after the operation.
We proposed a new classification of intra scrotal tumors according to the site of origin. Including our case, 56 cases of primary tumors of the scrotal wall have been reported in the Japanese literature. The diagnostic, therapeutic and prognostic problems were discussed.

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