Perforin is considered to be one of the important cytolytic factors found in the granules of killer cells. In this paper we attempted to demonstrate perforin in TIL (tumor infiltrating lymphocytes) of 55 human renal cell cancer cases and the perforin was proved by staining immunohistochemically with an anti-PFP monoclonal antibody. The result indicated that perforin was observed in 98% of the cases, while few positive cell was found in normal renal tissues. TILs were further characterized into their subsets including CD4⁺ T cells, CD8⁺ T cells, NK cells and γ/δ T cells using antibodies specific to their surface markers. The antibodies used are anti-Lew3a, anti-Lew2a, anti-Lew19 and anti-delta chain antibody. The former two subsets were predominantly found to be infiltrating in the tumor tissue, while the latter two subsets were shown to be lesser than the former. For examination of the correlation between the presence of perforin and the characteristics of infiltrated lymphocyte subsets, double-staining of the cells was performed using anti-perforin and one of anti-surface marker antibodies, respectively. The perforin was found to be expressed on the four subsets at different extent. A stronger reactivity of the perforin was found in the CD4⁺ T cells and CD8+ T cells than that in the NK cells and the γ/δ T cells.
These findings suggest that perforin may play a role of effector functions in the immunological defense mechanism against cancer. To define the significance of the expression of the perforin not only on the CD8+ T cells but also on the CD4+ T cells is required for further study.

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In order to determine a reliable method for measuring oxalic acid, we carried out a procedure using high performance liquid chromatography. This method proved to be excellent in the case of tea and beer. In the case of urine, however, it had some problem from the aspect of reproducibility, although as far as linearity measurement, dilution test and recovery rate were concerned, accurate results could be obtained. Nevertheless, this method was thought to be unsuitable for routine clinical use, at least at present, for the reasons that it took a long time to perform the measurement, and because of the high cost of the column used in the procedure.
The value of the oxalic acid as determined by this method in 24hr urine from 12 healthy male volunteers was in the range of 17-47mg/day (average±standard deviation: 25.4±9.0). To correct for their differences of physical constitution, dividing exalic acid value by body weight rather than by urinary creatinine or body surface area was found to give a more precise value of the norm. From this calculation, it was thought that the normal range of oxalic acid value was 0.6mg/kg or less.

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From November 1991 through January 1993, we performed laparoscopic lymphadenectomy on 10 patients. These patients were aged 54 to 77 years. All laparoscopic procedures were performed under general anesthesia. We dissected obturator lymphnodes on bilateral side. Total operation time ranged from 127 to 325 minutes. We could excise 3 to 9 lymph nodes on right side and 0 to 10 lymph nodes on left side. Blood loss was 180ml in one patient, but minimal in the remaining 9 patients. Ureteral injury occurred during laparoscopic procedure in one patient. This injury could be managed with laparoscopic and cystoscopic procedure. Postoperatively complications were observed in 5 procedures, which consisted of subcutaneous emphysema in 2 procedures, fever (over 38°C) in 2, shoulder and arm pain in 1, ileus in 1. The patient with ileus complained of abdominal fullness but he was able to ingest. All patients resumed their preoperative activity by postoperative day 3 to 5. We believe that this procedure was safe and useful for decision making in the management of our patients. We need further study on indications and techniques for this procedure.

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It has been reported that there is no relationship between serum testosterone level and erectile function and that testosterone mainly acts on the brain and not on the penis. However, we have found that erectile dysfunction in some patients with low serum testosterone improved after androgen replacement therapy. We therefore studied the effects of testosterone on the contraction and relaxation of the corpus cavernosum penis.
Four groups of rabbits were studied over a similar time span. The testosterone group were non-operated and received testosterone propionate 10mg/day for 14 days before sacrifice. Two groups (castration+testosterone group and castration group) were castrated 28 days before sacrifice. The castration group received sesami oil for 14 days, and the castration+testosterone group received testosterone 10mg/day for 14 days. Entire penises were removed immediately after death by desanguination and dissected to obtain corpus cavernosum strips. These strips were suspended under 1g tension in a 20ml organbath containing Tyrode's solution. After equilibration for 2 hours, the addition of drugs was started. Changes in tension were monitored with an isometric transducer and recorded.
The vasoactive drugs used were norepinephrine bitartrate, 1-phenylephrine hydrochloride, clonidine hydrochloride, acetylcholine chloride and vasoactive in testinal polypeptide.
The contractility of the corpus cavernosum strips increased significantly in the testosterone group and the castration+testosterone group, but decreased significantly in the castration group as compared with the control after adding norepinephrine, phenylephrine and clonidine. Relaxation of the corpus cavenosum strips increased significantly in the testosterone group and the castration+testosterone group, but decreased significantly in the castration group as compared with the control after by adding acetylcholine and vasoactive intestinal polypeptide.
These results suggest that testosterone plays an important role in erectile function by a direct action on the corpus cavernosum penis.

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From 1970 to 1992, 23 patients were treated with irradiation for palliation of pain caused by bone metastases from hormone refractory adenocarcinoma of the prostate at Cancer Institute Hospital. External beam irradiation was delivered to painful bony metastatic sites using linear accelerator. Numbers of irradiated sites were 1, 2, 3 in 6 patients, 4 in 3 patients and 5 or 7 in one patient. To evaluate the pain relief at the irradiated sites, severity and frequency of pain were measured quantitatively before and 1 month after the treatment. Overall efficacy of palliation was evaluated by summing up results of the irradiated sites in each patient.
Pain relief was obtained in all the irradiated sites. Minimal relief, partial relief and complete relief of pain were achieved in 10%, 15% and 75% of the 60 irradiated sites, respectively. No significant dose-response relationship was observed. Complete pain relief was attained less frequently at the sites with severe and constant pain than those with moderate and intermittent pain. Minimal, partial and complete palliation of pain was attained in 9%, 17% and 74% of 23 patients, respectively. In patients with highly extensive bone metastases, many irradiated sites, or many irradiated bones, complete palliation was difficult to obtain. Recurrence of pain was observed in one site. In other 59 irradiated sites, pain relief lasted until patient's death or throughout the follow-up period (maximum 51 months, median 9 months). We concluded that external beam irradiation is an effective palliation therapy for pain of bone metastases from hormone refractory prostate cancer and will play a considerable role in the management of advanced disease.

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The effects of changes in extracellular pH and treatments with diuretics or some organic acids on the uptake of oxalate were studied in an epithelial cell line of renal origin (LLC-PK1 cells). The oxalateuptake into the cells exhibited a marked sensitivity to extracellular, pH, in the present results with acidic pH stimulating and alkaline pH inhibiting the DIDS sensitive uptakes. The uptake of oxalate was clearly inhibited by DIDS, proportionally to the concentrations from 10μM to 1mM. Furosemide, cholorothiazide, probenecid and acetazolamide inhibited the oxalate uptake significantly. Probenecid has the most potency on the inhibition of the uptake in high concentrations, and acetazolamide needed a high concentration for the small effect. However, allopurinol has no effect on the uptake as well as dicarboxylates. (malate, succinate and phenyl succinate) and organic acids (urate and para-amino hippurate).
We discussed the mechanisms of the inhibition against the oxalate uptake concerning with each drug. It was suggested that probenecid may inhibit the oxalate carriers directly, while furosemide, chlorothiazide and acetazolamide may inhibit then by the direct actions and some secondary effects which are provided by those drugs.

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Thirty-one cases with clinical Stage I testicular tumor were treated by surveillance policy after orchiectomy alone at Cancer Institute Hospital from April in 1985 to October in 1991.
Histological types were seminoma in 22 cases and nonseminomatous germ cell tumors (NSGCT) in 9. Relapses were observed in 7 (22.5%) patients between 2.5 and 9.3 months after orchiectomy.
Five (22.7%) of 22 seminoma and 2 (22.4%) of 9 NSGCT recurred and received further cis-platin based chemotherapy. In all of 5 seminoma and one of NSGCT cases recurrences developed in the retroperitoneal lymph nodes and in another NSGCT case lung metastasis was observed.
All patients have been treated with success and are alive without evidence of disease between 5 and 48 months after salvage therapy. One of the recurrent cases with seminoma had an evident retroperitoneal metastasis missdiagnosed as the small intestine at staging retrospectively. And 2 of 3 seminoma cases and one of 2 NSGCT cases with minimally abnormal findings in the retroperitoneal lymph nodes had recurred. Surveillance policy may not be adequate for patients with these changes.
But overall survival rate of stage I testicular tumors were estimated 100%. And relapse were observed in a small number of stage I without “minimally changes”. So we regarded that surveillance policy was valid in patients with clinical stage I testicular tumor under careful staging and intensive follow up.

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Bladder capacity, nocturnal urinary volume and nocturnal urinary behavior were investigated in 1751 nonenuretic and 282 enuretic children in two primary schools and four kindergartens. The results were as follows:
1. A statistically significant linear correlation was observed between the age and the bladder capacity in the morning and daytime, as well as nocturnal urinary output, in nonenuretic children.
2. The bladder capacity of enuretic children was smaller in the ages below 6 but larger in the ages over 7 than that of noneuretic children. It was not likely from this evidence that an immature bladder capacity was a primary cause of enuresis.
3. For the estimation of the maximum bladder capacity in the study of enuresis, urinary output in the morning immediately after awakening with sufficient urinary sensation was thought to be more reasonable than that in the daytime, because output in the morning was approximately 50% more than that of the daytime.
4. Ten to 15% of nonenuretic children showed nocturnal polyuria with nocturnal urination after complete awakening more than one time every week. It was also not likely from this evidence that polyuria was a primary cause of enuresis.
5. The overall occurrence rate of enuresis was 14%, higher in males up to the ages of 9, and almost equal in males and females after the ages of 10.
6. The average age for the spontaneous disappearance of enuresis was 7.3 y. o., therefore, adequate treatments for enuresis should be instituted after the age of 8.

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We measured the amount of binding sites for endothelin-1 (ET-1) in the bladder and prostate in patients with and without benign prostatic hypertrophy (PH and NPH group) using ¹²⁵I-ET-1. Also the localization of ET-1 binding sites in hypertrophied adenoma was studied using autoradiography. Saturation experiments with ¹²⁵I-ET-1 revealed that there were single class of saturable high affinity binding sites for ¹²⁵I-ET1 in the homogenate of the bladder (dome and base) and prostate (adenoma and capsule). The K_D values to the bladder and prostate were not different between PH and NPH group. The Bmax values in the bladder (base and dome) were significantly lower in the PH group. While those in the prostate (adenoma and capsule) were significantly higher in the PH group. Autoradiograms of hypertrophied adenoma showed that ET-1 binding sites were localized to the stromal smooth muscles as well as to the glandular epithelium. These data suggest that ETs affect the pathophysiology of BPH through the changes in receptor density in both the bladder and prostate.

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Obliterative arteriopathy is one of the major obstacles to long-term survival of human renal allografts. However, the cellular composition of obliterative arteriopathy has been incompletely characterized. We have performed immunocytochemical investigations of cellular components of obliterative arteriopathy and also investigated immunophenotypic features of proliferating smooth muscle cells in these lesions.
Three renal allografts that had been removed due to rejection were available for this study. Time lapse between transplantation and removal of the renal allograft in these patients was 2 months, 5 months, and 4 years and 9 months, respectively. Tissue blocks cut from these renal allografts were fixed in methanol-Carnoy's fixative, and embedded in paraffin. Serial sections from each block were cut and used for histopathological and immunocytochemical studies. Monoclonal antibodies used for this study were as follows: anti-muscle actin antibody, HHF35; anti-smooth muscle actin antibody, CGA7; anti-vimentin antibody; anti-desmin antibody; anti-macrophage antibody, HAM56; and anti-Factor VIII-related antigen antibody.
In all the allografts, obliterative arteriopathy was observed in the interlobular and arcuate arteries. In an early stage of proliferative lesions (2 months), the hyperplastic intima consisted largely of macrophages, intermixed with smooth muscle cells. At this stage, smooth muscle cells at the luminal site stained positive with HHF35, but negative with CGA7. In older lesions (5 months, 4 years and 9 months), however, the thickened intima consisted almost entirely of smooth muscle cells. At this stage, smooth muscle cells stained positive with both HHF35 and CGA7.
These findings suggest that 1) macrophage may play an important role in an early stage of obliterative arteriopathy and 2) an immunophenotypic expression of intimal smooth muscle cells in obliterative arteriopathy may be different between young and older lesions.

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CT scans were carried out on 25 patients with transitional cell carcinoma of the renal pelvis. Of the 25 patients, tumors were identified in 24 patients (96%) and not in one patient on CT scan. Of the 24 patients the tumor was delineated as a solid mass in the renal pelvis and/or calyx in 15 and as an infiltrating mass in the renal parenchyma in 8 on CT scan. The depth of invasion was correctly estimated by CT in 18 of the 25 patients (72%), whereas the tunica muscularis of the renal pelvis or the renal parenchyma was found involved in 3 of 10 patients (30%) in whom the diagnosis was made that the tumor was limited to the renal pelvic mucosa, the correct diagnosis was possible in 22 of 25 patients (88%) in whom the tumor was confined to the renal pelvic wall (pTa-pT2) or more invasive (pT3-pT4). In 6 of 7 patients with lymph nodes matastases enlarged lymph nodes were seen on the CT scan. In all 7 cases the primary tumor was classified as a pT3 or pT4 invasive disease. Based on the results presented above, it may be concluded that CT scan is valuable in making the diagnosis of transitional cell carcinoma of the renal pelvis and also in determining whether the tumor has invaded beyond the renal pelvic wall, thereby providing guidelines for the adequate treatment.

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A review of 611 cases of renal pelvic or ureter tumor registered in Tokai Urological Tumor Registry for the past 10 years from 1980 and comparison of results between the first and latter half was made. The number of renal pelvis tumor was 347 and that of ureter tumors was 264. Clinical stages and pathological grades of the tumor were as follows; Ta, 11.9; T1, 31.8; T2, 14.4; T3, 24.3; T4, 17.6% and G1, 10.5; G2, 49.3; G3, 33.0%. Higher stages and grades were observed in the recent 5 years. Of 409 cases (66.9% in total cases) treated by total nephroureterectomy, 28.3% of the first and 49.0% of the latter half were treated adjunctively by chemotherapy. Five years relative survival rates of these two groups were 49.4 and 47.3%, respectively, suggesting no improved results. A new treatment strategy such as neoadjuvant chemotherapy or lymphadenectomy is expected to improve the prognosis.

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An analysis has been undertaken to determine chronological changes that have occurred in the clinical features and treatments of advanced renal cell carcinomas. To accomplish this, 96 renal cell carcinoma cases, handled by the authors' department and at the branch hospital, were divided into two groups: 48 patients treated between 1975 and 1983 (group 1) and 48 patients treated between 1984 and 1991 (group 2).
Between the two groups, no differences were seen in the sex ratio, the mean age, and the ratio of those who were found to be advanced cases at the time of diagnosis and those whose cancers had advanced after undergoing a nephrectomy. Concerning treatment, interferon (IFN) and UFT were more frequently used in treating group 2 than group 1, and chemothrapy, radiotherapy, and endocrine therapy less frequently used. No differences were seen in the prognosis between the two groups; however, in those who had advanced after nephrectomy, group 2 cases survived for a significantly longer period than did group 1 cases. Patients who survived for 5 years or longer accounted for two cases in group 1 and 5 cases in group 2 and combination therapies involving surgery, IFN, UFT, or similar medications were used for their treatments.
These results suggest that adjuvant therapies, such as surgery, IFN, and UFT, have possibly contributed to prolonging survival, especially for cases that advanced after nephrectomy.

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Although the efficacy of OKT3 monoclonal antibody (OKT3) upon the steroid resistant rejection is well known, its beneficial effect on long-term result of kidney transplantation has not yet been well examined in Japan. A retrospective group study was performed to analyze the effect of OKT3 on the cadaver kidney allograft. Between September 1987 and October 1990, a total of 77 patients from four different hospitals were classified into 2 groups. Thirty-four patients from 2 hospitals were entered OKT3 therapy group and 43 patients from the other hospitals were entered steroid therapy group. Initial immunosuppression comprised low-dose cyclosporine (6mg/kg), steroid and antilymphocyte globulin in both groups. In OKT3 therapy group, acute rejection episodes those were considered steroid resistant were observed in 7 patients. They were treated with OKT3 monoclonal antibody. Of the seven patients, six recovered normal renal function. The mild rejection in OKT3 therapy group was treated with high-dose steroid. Minimal follow-up was 2 years. The 2-year graft survival was 82.4% in OKT3 therapy group and 74.4% in steroid therapy group. Although the improvement on the 2 year graft survival with OKT3 treatment was 8%, the difference between two groups was not statistically significant.

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Blood level monitoring of FK506 was performed on 6 kidney transplant recipients. Reproducibility was evaluated on trough and AUC levels in both whole blood and plasma samples. Reproducibility was almost the same degree on both trough and AUC levels and in both whole blood and plasma samples.
Trough and AUC levels in whole blood and AUC in plasma were low at the onset of rejection episodes, whereas those were high at the onset of adverse effects by FK506 such as hyperglycemia, hyperkalemia and neurological symptoms.
Frequent trough level monitoring is useful to detect kidney transplant rejection and adverse effects by FK506.

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From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200mg/body), and 28 paitents (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100mg/m²) and THP-ADM (40mg/m²) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP.
Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.
Transient elevation of serum creatinine was observed in 45% of the patients in group A. However, hematological toxicity such as leukocytopenia (<3000) and anemia (Hb<10gr/dl) were observed in 93% and 33% of the patients in group B. Since side effects were relatively mild in group A and there were no significant differences in the effects between these two methods, it was concluded that single injection of CDDP from the internal iliac artery was preferable to double injection of the agents for the treatment of locally advanced bladder cancer.

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The c-erbB-2 proto-oncogene product is expressed in adenocarcinomas of breast cancer and ovarian cancer, and its significance as a prognostic factor has been increasingly noted. We immunohistochemically studied the expression of c-erbB-2 proto-oncogene product using anti-c-erbB-2 gene product polyclonal antibody (Nichirei), which was produced using a synthetic peptide at the C-terminal portion as the immunogen. The subjects consisted of 52 patients with prostatic cancer who were treated at the Department of Urology, Shiga University of Medical Science, from 1982 to 1990. The expression of c-erbB-2 gene was observed in 40 of the 52 patients (76.9%). The positive rate was highest in patients with poorly differentiated cancer and in stage D2 patients, but there were no significant differences in positive rates among patients with different histological types or clinical stages. The probability that progression would occur was significantly (p<0.05) lower in the group that tested positive for c-erbB-2 than in the group that tested negative among 33 stage D2 patients after 5 years of treatment. When causespecific survival rates were calculated using the Kaplan-Meier method, the group that tested positive had a significantly (p<0.001) poorer outcome than the group that tested negative after 3 years and 6 months of treatment.
The above results suggest that c-erbB-2 expression in prostatic cancer may be useful in predicting the prognosis of the disease.

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We sometimes experienced infertile patients whose sperms had no motility but were not stained by Eosin Y. In this paper we report five cases of so-called “immotile spermatozoa”. The ultrastructure of sperm tails was examined by transmission electrone microscope (TEM). These cases were selected from the out-patient population who attended inferitility clinic of our department. The semen analyses showed that all the cases had sperm motility below 1% and more than 90% of the spermatozoa were proven alive. Family history revealed that one case had an inferitile sibling. None of them had situs inversus, bronchiectasis and chronic sinusitis which are classic trias of Kartagener's syndrome. They had no symptoms of upper respiratory tract infection which was caused by the abnormality in the flagella of the respiratory tract. The TEM pictures of sperm tails showed partial deletion of inner dynein arms in two cases, lack of central microtubular doublets (so-called 9+0) in two cases and disarrangement of microtubular doublets in one case. For the treatment of these cases there is no effective means but AID. However, the rapid progress of IVF-ET techniques and a report that the spermatozoa from Kartagener's syndrome had showed penetration into eggs encoureged us to think the micromanipulation of spermatozoa with IVF-ET as a hopeful option of the treatment in the near future.

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A 54-year-old female suffered from repeated flank pain. A large, irregular cystic mass that compressed and distorted the left pelviocalyceal system was found. She underwent left nephrectomy. The cyst arised from the inner zone of the kidney. Although monolocular grossly, it was compatible with the multilocular cystic nephroma on the microscopic examination.

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We reported a case of epididymal sarcoidosis. The patient was a 13-year-old boy with a chief complaint of right scrotal mass. On physical examination, a firm, nontender 7mm mass was palpable in the right hemiscrotum and appeared to involve the head of the epididymis. Ultrasonography showed a highly echogenic mass in the epididymis. A routine chest X-ray revealed lymphadenopathy of the mediastinum and reticular shadows in bilateral lung fields. Because the lesion might be confined to the epididymis, a partial epididymectomy was performed. The histopathologic specimen showed noncaseating granulomas consistent with sarcoidosis. Lung biopsies also revealed noncaseating granulomas. Subsequent pulmonary function studies revealed a mild obstructing ventiratory defect, therefore therapy was instituted with systemic steroids. There were no further recurrent scrotal masses.
Although sarcoidosis is known to affect many organs, involvement of the genital system is relatively rare. Most of the patients with intrascrotal sarcoid lesions have an abnormal chest X-ray. We need to differentiate these lesions from advanced testicular cancer. This is the 5th case of intrascrotal sarcoidosis in Japanese literature.

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