Serum levels of prostatic acid phosphatase (PAP), γ-seminoprotein (γ-Sm) and prostate-specific antigen (PSA) were determined simultaneously in 57 patients with benign prostatic hyperplasia (BPH) and in 50 untreated patients with prostatic cancer (adenocarcinoma, N=47 and non-adenocarcinoma, N=3). The correlations between the serum levels of γ-Sm and PSA in these patients were assessed by linear regression analysis. Some fundamental studies were added for explaining the causes of discrepancy between the serum levels of γ-Sm and PSA.
All of BPH group underwent transurethral resection of the prostate (TURP) and the sera were obtained for measurements before, immediately after and 18 hours after TURP. The γ-Sm correlated well with the PSA in the sera obtained before (r=0.76) and 18 hours after (r=0.73) TURP. However, there was no correlation (r=0.26) between them in the sera obtained immediately after TURP.
In 47 untreated patients with adenocarcinoma of the prostate, no significant correlation (r=0.19) between serum levels of γ-Sm and PSA was observed, although there was correlation (r=0.51) between those of PAP and PSA. When these patients were classified into two groups, M₀ (stage A-C; N=26) and M₁ (stage D; N=21), however, the serum γ-Sm correlated with the serum PSA in M₀ group (r=0.57), but didn't in M₁ group (r=0.11). Furthermore, the differences in the means of PAP (p<0.05) and PSA (p<0.001) between M₀ group and M₁ group were statistically significant, although the serum γ-Sm failed to distinguish M₀ from M₁.
The anti-PSA antibody of “PSA Kit” reacted against the standard γ-Sm adopted from “γ-Sm Kit”. Surprisingly, the anti-γ-Sm antibody of “γ-Sm Kit” also reacted against the standard PSA adopted from “PSA Kit”. The γ-Sm and PSA apparently cross-reacted each other. The quantitative analyses with serial dilution of the sera were done by using each assay in 3 patients whose serum levels of γ-Sm were markedly different from those of PSA. The dilution curve for PAP appeared to be rectilineal, and that for PSA also appeared to be approximately rectilineal. However, the γ-Sm assay failed to be proportional.
In conclusion, the correlation between serum levels of γ-Sm and PSA was absent in certain circumstances, when the true values of them were expected to be much higher than those determined. At present, the role of available assay for serum γ-Sm appears to be limited for determining the true value.

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An acridine orange cytofluorometric analysis was used to study the DNA-RNA contents of bladder washing exfoliated cells from 109 patients with transitional cell carcinoma of the urinary bladder. DNA and RNA measurements were performed in each of 200-300 cells/sample, and DNA index (DI) and RNA index (RI) were calculated from the distributions of these values. Presence of aneuploid stem cell line and/or increased mean DNA contents were observed in 83 (76.1%) of the 109 patients. Elevated RNA content in a diploid cell population, was of no additional diagnostic significance. Histologically diagnosed high grade and high stage bladder carcinoma apparently showed an aneuploid stem cell line with high DI and high RI. Thirty patients with superficial bladder cancer (Ta and T1) who had tumor recurrence within 2 years after surgical interventions showed a significantly increased RI in contrast to 10 patients who had no recurrence for more than 2 years. RNA content measurement was thought to be useful for prediction of tumor recurrence after surgical interventions. Six patients who had a progression from superficial to invasive cancinoma were with high histological malignancy, lamina propria invasion, high DI and high RI. However, there was no significant difference in RI between the 6 patients and the other patients with superficial bladder cancer. Eight patients who had distant metastasis within one year after radical cystectomy also showed a significant increase in RI in contrast to 8 patients who had no metastasis for more than 1 year. Increased RI may be said to be an impotant risk factor in predicting the development of distant metastasis and recurrent tumor after surgical interventions.

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Prevalence of micturition problems among 1, 023 institutionalized elderly was surveyed by a questionnaire. The reply was obtained from 821 elderly (80.3%) including 276 males and 545 females with ages averaged 77 years (range 61 to 96 years). They had neither highly impaired performance status nor severe dementia.
Micturition problems were complained by 38% of male responders, where micturition difficulty was the most common. On the other hand, 23% of female responders answered having micturition problems and urinary frequency was the most common. One hundred and twenty-four of total responders (15%) replied to have urinary incontinence; 8% in men and 19% in women. Over half of patients with marked objective incontinence denied its presence or refused to answer. Seventy-one per cent of the incontinent elderly had no intention to receive medical care.
From the above facts, it seems that many elderly have micturition problems and the incidence of urinary incontinence is latently higher than complained at survey.

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We have previously suggested that an appearance of FDP D-dimer fragment into the urine predicts the reversibility of acute renal transplant rejection. In the present study, we observed urinary tissue-type plasminogen activator (tPA), which is a fibrinolytic enzyme and produces D-dimer, in 51 renal transplantation patients. Urinary tPA values are generally higher in transplantation patients except on chronic rejection than in healthy controls. High values just before onset of rejection (increase of serum creatinine value), deterioration at onset phase and gradual elevation from peak phase toward recovery phase were observed in urinary tPA of 6 reversible acute rejection episodes.
Urinary D-dimer values changed following urinary tPA values in serial observation of 2 cases. In conclusion, immunological reaction accompanying by functional and organic renal impediments may result in loss of fibrinolytic activity, decrease in urinary tPA and D-dimer. This findings suggest theoretically that the supplemental tPA administration prevents the progression of rejection reaction.

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The binding sites of lectins in parathyroid glands were determined by an immunohistochmical method in normal parathyroid gland, hyperplasia, adenoma and carcinoma, the used lectins were commercially available Glycine max (SBA), Concanavalina enciformis (Con A), Triticum vulgaris (WGA), Richinus communis (RCA), Banderiaea simplicifolia II (BSA II) and Arachis hypogaea (PNA). For normal parathyroid glands (2 cases) and hyperplasia (2 cases), WGA and BSA II were stained in cytoplasma and cell membrane. For carcinoma (1 cases), all lectins but BSA II were positively stained. In particular, SBA revealed more stronger stain than any other hystological types. From the staining patterns of lectins, it was suggested that adenomas (22 cases) be divided into one group similar to carcinoma and the others to normal parathyroid gland and hyperplasia. But there was no difference in clinical data of patients between the two groups.

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The pathological features and clinical outcome of grade 3 transitional cell carcinoma of the bladder, excluding CIS, encountered between 1972 and 1988 were studied to clarify the clinical characteristics of the disease. The subjects of this study were 108 patients consisting of 76 males and 32 females aged 33-87 years, with a mean age of 66 years. The survival rate according to each factor was calculated by Kaplan-Meier method, and the survival curves were compared by generalized Wilcoxon test.
Grade 3 bladder cancer was often papillary, sessile and about 3cm in diameter and showed a tendency of multiple occurrence. Histopathologically, it was often in high stages of pT2 or above and frequently with vascular invasion.
Total cystectomy is not considered to be an absolute necessity for pT1, G3 bladder cancer patient, because, in our experience, it did not improve the prognosis. However, bladder-preserving operation requires strict postoperative follow-ups. After this operation, the 5-year survival rate was higher in the no-recurrence group than in the recurrence group, and the out come tended to be better in the group that had undergone intravesical instillation chemotherapy for prevention of recurrence than in the group without this therapy. Ample intravesical insitllation chemotherapy after bladder-preserving operation seems to improve the postoperative course of bladder cancer patients. Total cystectomy may be unavoidable in patients with pT2 or above, and no effect of postoperative adjuvant chemotherapy was noted in our series. The establishment of multidiciplinary approaches is considered to be needed for improvement of the prognosis of high stage bladder cancer.

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Parathyroid hormone related protein (PTHrP) is the main factor of humoral hypercalcemia of malignancy (HHM). Using anti-PTHrP monoclonal antibody 4B3, we investigated the immunohistochemical localization of PTHrP in human normal renal tissues and renal cell carcinomas.
Among normal renal tissues, distal tubules and collecting ducts showed positive immunostaining. Among 36 cases of renal cell carcinoma, PTHrP was detected in 30 cases (83%), and there was no significant correlation between the degree of the immunostaining and the serum calcium levels of the patients. As for the histopathological types of the renal cell carcinomas, granular cell subtypes tended to be more strongly positive than clear cell ones.
In conclusion, it was not uncommon that PTHrP was commonly presented by renal cell carcinoma, and HHM occurred when the PTHrP transgressed the homeostatic mechanisms.

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To investigate the roll of c-myc protooncogene in human bladder cancer, c-myc gene was transfected into T-24 human bladder cancer cells and the changes of cell characteristics were studied. C-myc gene transfection was performed, using the electroporation method decribed previously (J. J. Urology, 80, 1989). After electroporation, c-myc gene was transfected and neo ^(r) cells were cloned in a neomycin containing medium. One typical cloned cell (myc-cl₃) was obtained. And this cell clone was shown to contain more than 3 extra-copies of c-myc gene by Southern blotting analysis. Morphology and growth speed of the myc-cl₃ cells were not significantly different from those of original T-24 cells. However, they easily made overlapped cell-layers in the cofluent growth phase. In the soft-agarose semi-solid medium, myc-cl₃ cells formed about 35 times more numerous colonies than T-24 cells. Myc-cl₃ cells also formed tumors on nude-mice at a significantly higher rate than T-24 cells did.
These results suggest that c-myc gene plays a key roll in clonal growth and tumor formation in human bladder cancer.

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We measured epidermal growth factor (EGF) in the urine of 54 untreated patients with malignant tumors (7 prostatic cancer, 11 renal tumor, 31 bladder cancer, 3 renal pelvic tumor, 2 ureter tumor) in the Toyama Medical & Pharmaceutical University Hospital. We also measured EGF in the urine of 77 normal subjects (43 males, 34 females).
Urinary concentration of EGF in normal subjects decreased with increasing age. It was significantly higher in females than males (p<0.05). Urinary concentration of EGF in patients with prostatic cancer or renal tumor was similar to that in normal subjects. The patients with prostatic cancer controlled by estrogen showed a slightly high level of EGF in the urine. In patients with renal tumor, urinary concentration of EGF decreased after nephrectomy. Patients with bladder cancer showed a significant decrease of EGF in the urine compared with normal subjects (p<0.05), and urinary concentration of EGF in the patients with bladder cancer of high stage was remarkably low. Low concentration of EGF in the urine was recognized in patients with renal pelvic tumor or ureter tumor. However, the relationship between the decrease of urinary concentration of EGF in these urothelial tumors and the growth of these tumors remains to be elucidated.

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Thirty-one patients with intervertebral disc prolapse (IDP) underwent urodynamic study before surgical operation. The lesion was located between C4 and T10 in 14, T11 and L2 in 2 and L2 and S1 in 15 patients. Preoperative urinary symptoms were obstructive in 11 (36%), irritative in 5 (16%) and both obstructive and irritative in 5 (16%) patients, and the remaining 19 patients (32%) had no symptoms. Preoperative urodynamic abnormalities were noted in 23 cases (74%): abnormal urinary uroflow in 6 of 14 cases (43%), residual urine of more than 30ml in 9 of 31 cases (29%), abnormal cystometrogram and/or external sphincter EMG in 16 of 31 cases (52%). These urodynamic abnormalities were closely correlated with perineal hyposensitivity.
Voiding function was re-examined in 22 patients after operation: improved in 14 (64%), unchanged in 1 (4%), worsoned in 2 (9%) and normal in 5 (23%) before and after operation. Therefore the above results could indicate that the presence of perineal hyposensitivity should be suspected to have voiding dysfunction in patients with IDP. Orthopedic surgery may improve voiding dysfunction in the majority of patients.

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Renal cell carcinomas (RCCs) frequently metastasize to distant organs in their clinical course. However, the mechanism of the metastasis had not been fully elucidated. In vitro invasion assay has been reported to be a rapid method for the evaluation of the invasive potential of various malignant cells. In vitro invasive potential of RCC has not been investigated by this method. Thus, in the present study, we first attempted to characterize the in vitro invasive potential of four human RCC cell lines which had been established in our institute. Secondly, we investigated the influence of two growth factors (EGF, TGF-β1) on the invasive potential of these cell lines when the two factors were applied as chemoattractants.
SMKT-R-3 and R-4 cell lines showed more cell penetration through Matrigel than SMKT-R-1 and R-2 cell lines, suggesting that the former cell lines have higher invasive potential.
While invasive potential varied in each cell line, it was enhanced by EGF in all cell lines. However, TGF-β1 suppressed the invasive potential of all four cell lines. These results suggest that two factors have different actions on the invasion of RCCs.

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To minimize urothelial tissue injuries by inadvertent laser irradiation during the laser stone fragmentation, we developed a novel fiber-optic analysis system which is able to distinguish the urothelial tissues from urinary stones. The reflection mode of the pulsed photo-thermal radiometry (PPTR) was employed for non-destructive tissue characterization. We developed the first fiber-optic PPTR system using chalcogenide infrared glass fibers as a transmission line. As excitation light sources for the samples, three different lasers were used in vitro and compared to select the proper excitation laser which is able to distinguish wet urinary stones from urothelial tissues. The e-folding decay time of the PPTR waveform, by which the samples are characterized, was measured as an index. The ultraviolet argon (UV Ar) laser had the best discriminative faculty. Using uv Ar laser, the e-folding decay time of calcium oxalate stones, uric acid stones and the ureter, was 239±57ms, 33±4ms, and 102±24ms (p<0.001), respectively.
The new analysis system which was composed of the fiber-optic PPTR analyzer using UV Ar laser excitation together with a thin-fibered endoscope was applied to measure the e-folding decay time of PPTR waveform of urinary stones and canine ureters in vivo general anesthesia. The e-folding decay time of calcium oxalate stones, uric acid stones and the ureter was 153±15ms, 26±3ms and 246±31ms, respectively. The canine ureter was clearly differentiable from urinary stones by the measurement of the e-folding decay time of PPTR waveform. This fiber-optic analysis system may be useful for the prophylaxis is inadvertent irradiation to the surrounding tissue during the laser stone fragmentation.

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A stretch test in vivo for living material was newly developed and applied to the dog bladder. The stress-strain curve of the bladder was speed-dependent and with hysteresis. The mechanical properties of the bladder in vivo was essentially viscoelastic.
The stress-strain curve of a normal living bladder was downward convex and rose very slowly. On the other hand, that of an extirpated bladder or neurogenic bladder after denervation of the pelvic nerves demonstrated a rapid elevation.
A computer analysis based on a visco-elastic simulation model proposed by Glantz was carried out to evaluate changes of the curve under various conditions, which successfully demonstrated the mechanical properties of the bladder. The model proposed by Glantz explained the mechanical properties of the bladder wall.
The following formula represented the stress-strain curve by the model:
φ=-β(φ+α)²/γ+β(φ+α)C+α²βe^βct/γ
φ: force, α & β: elastic constant, γ: viscous constant.
According to their properties, α was designated as proportional stiffness and β as exponential stiffness.
The three constants, α, β and γ for the stress-strain curve obtained experimentally from the bladder under different conditions were calculated by computer analysis. Both proportional and exponential stiffness elevated in the extirpated bladder. In the denervated bladder, changes of the constants were not significant immediately after cutting the pelvic nerves. However, the proportional stiffness (α) elevated remarkably two weeks after the cutting. Compared with these abnormal bladders, the elastic constants in the normal living bladder were every low. The viscous constant did not change under any conditions that were examined in this study.
The visco-elastic properties of the bladder and its low elastic constants seemed to provide the normal bladder function in reservoir of urine.

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Cystometry may be considered as a stretch test for the bladder wall. In the 1st report, it was stated that the properties of the bladder were well explained as a visco-elastic model proposed by Glantz and a formula for the stress-strain curve was proposed. In this 2nd report, another formula representing theoretical cystometrogram derived from the former formula, is proposed.
Using this formula, the three constants (α, β, γ) of a normal living bladder, extirpated bladder and pelvic nerve-cutting bladder were calculated by computer analysis. They corresponded well to those obtained from the actual stress-strain curve of the bladder. Thus one can obtain these constants by computer analysis from an ordinary clinical cystometrogram without performing stretch test of the bladder.
The three constants in the formula at voiding were also calculated by the same computer analysis of voiding cystometrogram. Among the three, only the proportional stiffness (α) elevated 10 times higher at bladder contraction than that at relaxation. This fact suggests that the bladder can void automatically by its mechanical properties, when the proportional stiffness (α) is changed by the switching of nerve stimulation.
The detailed theory on the formula will be published in English elsewhere.

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Two cases of vasitis nodosa are reported hereon. The two patients were 47 and 40 year old males with desire of refertility. They were performed vasectomy 23 and 10 years ago. They were subjected to vaso-vasostomy. During the operations, spindle shaped nodules were found in the vas deferens at the site of the previous vasectomy. Histologically, they showed focal proliferation of epithelial components forming glands, where a plentiful number of sperms were present, and this was also associated with proliferative change of smooth muscle bundles of vas deferens. Some foci of spermatic granulomas were also found. This condition was similiar those of salpingitis isthmica nodosa in the fallopian tube. Vasitis nodosa should be differentiated from metastatic adenocarcinoma histologically. This condition may lead to re-canalization.

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Twenty-nine cases of bone metastases from renal cell carcinoma were examined. Eight had metastatic bone pain as the initial symptom and were diagnosed that the primary lesion was in a kidney. In eight cases bone metastases appeared after treatment of the primary site. Seven had only bone meatasases and another 22 cases had multiple metastases in organs such as the lung and lymph node when the bone metastasis was found. Curable surgical treatment was performed in only 2 cases. The survival curve of these patients were: 1 year; 41 per cent, 2 year; 30 per cent and 3 year; 15 per cent.
Bone scan used for detection of bone metastases of carcinoma frequently ends with false positive results. CT scan and angiography are available for differential diagnosis of bone metastasis. We examined 6 cases (9 lesions) of bone metastases from renal cell carcinoma (3 pelvic bones, 2 lumbar bones, 2 femurs and 2 humerus). All lesions were hypervascular by angiography and were easily diagnosed as bone metastases.
For early detection of bone metastases from renal cell carcinoma, angiography is useful because hypervascularity and tumor stain are easily detected even in such small lesions as 2cm. Angiography was also useful for chemoembolization.

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