In 1960, the beneficial effect on allograft survival of 6-mercaptopurine (6-MP) was demonstrated. In 1961, azathioprine, a less toxic derivative of 6-MP, was synthesized and soon became the main form of maintenance therapy. Around the same time, clinical studies of the effects of corticosteroids on the immune system were being conducted and successful reversal of rejection with cortisone was recognized. Subsequently, steroids were added to azathioprine and this regimen constituted maintenance immunosuppressive therapy in most centers for over 20 years. However, these first generation immunosuppressive medications are the cause of the majority of complications following renal transplantation. Both azathioprine and steroids effect nearly all immunologic and inflammatory responses and may predispose to infection and certain malignant diseases. Despite refinement in the use of these agents with improved patient survival, little improvement in graft survival was appreciated.
The second generation immunosuppressive agents, antilymphocyte globulin (ALG), emerged in the form of polyclonal antibodies derived from xenotypic antisera and directed against the entire cellular response. Unfortunately, many limitations have been encountered with respect to the administration of ALG.
Cyclosporine A is more specific and attacks a subset of the lymphocyte population, the T helper lymphocytes. When cyclosporine A is used in combination with prednisone, the immunologic cycle that causes rejection is interrupted twice by virtue of the fact that prednisone prevents the production of IL-1 by macrophages and cyclosporine A with the production of lymphokines, especially IL-2 (T-cell growth factor). Although cyclosporine A is at present better immunosuppressive drug to azathoprine, it is not without a number of side-effects. Nephrotoxicity, however, is the most worrying complication in patients receiving cyclosporine A. Of most importance to the urologist, however, is the interaction with cyclosporine A by many of the drugs used to treat various urologic infections.
The advent of hybridoma technology which has become so important to the urologic oncologist has also impacted upon transplantation and resulted in the development of a new generation of antilymphocyte antibodies. The bulk of clinical experience has been obtained with OKT3, a monoclonal antibody directed against the T3 antigen complex found on all T-lymphocytes. A large multi-center experience has showed the remarkable efficacy of OKT3 in providing rapid depletion of peripheral blood T cell levels and reversal of established rejection not responded to conventional high-dose steroid therapy and in reducing the frequency and delay of the onset of rejection reactions.

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Recent reports have shown the existence of renin in Leydig cells of the rat testis and immunoreactive renin activity in the human testis. But we could not rule out the possibility that the renin found in the testis is contamination of plasma components by endocytosis.
In the present study we tried to demonstrate the renin production in the human testis by the following experiments. At first, we measured the plasma renin activity and testosterone in the internal spermatic vein simultaneously after treatment with hCG and obtained the results that suggested hCG-induced renin secretion in the human testis. Nextly, we showed the hCG-dependent renin production from the cultured human Leydig cell tumors in vitro.
Thirdly, we demonstrated the existence of renin mRNA in the human testisusing reverse transcriptase-polymerase chain reaction (RT-PCR). Fourthly, we detected significant signals of human renin mRNA in the human testicular tissues by in situ hybridization.
From the above results, it was demonstrated that the human renin gene was hCG-dependently expressed in the human testis.

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To study the characters of bladder tumors which showed positive urinary cytologies, the results of urinary cytology of untreated bladder tumor patients in our hospital during 10 years between July 1980 and June 1990 were evaluated according to the degree of tumor differentiation, namely differentiated type which did not contain grade 3, and undifferentiated type which contained grade 3. Concerning the differentiated tumors, positive rate of cytology was 37.3% on the whole. Positive rates of multiple tumors or tumors around internal urethral orifice were significantly high, and those of tumors larger than 3cm, tumors located on posterior wall, left wall or throughout the entire surface, were higher than the overall positive rates.
Repeated examinations of yielded increased rates of positive cytology results. Concerning the undifferentiated tumors, the positive rate of cytology was 90.0% on the whole, was not influenced by tumor sizes or lacations, and was consistently observed irrespective of the number of times of cytologic examination.

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Statistic study was made on 685 outpatients with erectile dysfunction during 13 year periods from 1979 to 1991 in the Department of Urology, Takamatsu Red Cross Hospital. The age distribution showed the highest frequency in the thirties decade (27.9%).
1. Diagnosis
Nocturnal penile tumescence monitoring was the only method to distinguish organic impotence from functional impotence during the first 5 years. From 1984 we have been able to diagnose corporal veno-occlusive insufficiency (CVI) by papaverine test and dynamic infusion cavernosometry and cavernosography. Measurement of penile brachial index and pelvic angiography were performed to diagnose arterial insufficiency (AI). In neurological examination we have measured bulbo-cavernosus reflex latency and nerve conduction velocity of the dorsal penile nerve and performed microvibration measurement and sweat spots test. All diagnostic methods were established in 1987 and we have been able to classify about 80% patients. We classified 305 patients during the last 5 years from 1987 as follows: psychogenic; 31.1%, CVI; 20.0%, AI; 7.9%, neurogenic; 7.9%, others; 14.1%, drop-out and unknown; 19.0%.
2. Treatment
In the beginning only counseling and drug therapy were performed. However we lately performed various suitable methods for individuals based on their diagnoses. We performed counseling, drug therapy and intracavernous injection of vasoactive drug therapy for recovery of spontaneous erection (vascular training) for psychogenic IMP. The efficacy rate of counseling was low (30.4%) but that of drug therapy was 41.6%, and that of vascular training, 64.2%. For CVI without other factors we performed venous surgeries. Only about 25% of them perform sexual intercourse with or without self injection of vasoactive drug (self injection).
Treatment results for AI was not satisfactory because we could perform revascularisation only once. Though we recommended self injection or vacuum constriction device for impotents with neurological disorder or more than one factors, many patients refused it.

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The submucosally embedded in situ appendix guarantees an ideal continence mechanism in patients with ileocecal urinary reservoirs. To date this modification of the Mainz pouch technique was performed successfully in 10 patients between September 1990 and October 1992.
Pouch capacity ranged from 350ml to 900ml (mean: 565ml), frequency of intermittent self-catheterization ranged from 3 to 7 times per day (mean: 4.4-5.4 times) and complete urinary continence without difficulty of self-catheterization was obtained in eight patients. Two patients with stomal stenosis needed to indwell a catheter. The follow up periods ranged from 3 to 24 months (mean: 14.7 months).
The main advantages of appendix stoma technique are shorter operation time, a short ileal segment, no risk of nipple gliding or prolapse, no need for staples, thereby decreasing significantly the risk of stone formation, and facilitating easy catheterization. This method seemed to be valuable for continent urinary reservoir assuring patients of high quality of life.

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From 1988 to 1992, 78 patients with genuine stress urinary incontinence underwent bladder neck suspension under ultrasonical monitoring. Tightness of suspension was adjusted by setting posterior urethrovesical angle to approximately 90 degree by transrectal ultrasonography during operation. Urinary continence was achieved in 68 of 78 patients. In the remaining 10 patients, slight incontinence recurred within 6 months after operation. In 60 patients undergoing postoperative chain cystourethrogram, the posterior urethrovesical angles set during operation were about the same as those after operation. In 39 patients undergoing uroflowmetry under the condition that micturition volume was 200ml or more, urinary flow rate did not decrease after operation. In 20 patients whose posterior urethrovesical angles were measured by transperineal and transabdominal as well as transrectal ultrasonography, angles measured by each ultrasonography were almost identical and neither manipulation could change the configuration of the baldder neck. The posterior urethrovesical angles set during operation were kept postoperatively and provided proper tightness of the suspension suture to achieve urinary continence without any difficulty of urination. Therefore, a posterior urethrovesical angle can be set by transperineal and transabdominal ultrasonography as well as transrectal ultrasonography. While transrectal approach provides the clearest image among the three approaches, transperineal and transabdominal approach carried out with a transabdomial convex or sectorial probe are more convenient than transrectal approach which needed a special probe.

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Urinary incontinence following total prostatectomy was evaluated in 10 patients by urodynamics and lateral urethrography. The pathological stage of the tumors in these patients was pT₂ in 5 patients, pT₃ in 3 patients and pT₄ in 2 patients. Urinary incontinence was present in 8 patients, of whom 7 were stress incontinence and one was urege and stress incontinence. The severity of incontinence of these patients was mild in 5 patients, moderate in 3 and severe in 2. The incontinence was severer in the patients with the tumors of pT₃ or pT₄ than in the patients with the tumors of pT₂. But the severity of incontinence was not related to the pathological grade or resected weight of the tumors. The bladder capacity and bladder compliance were 214.9ml and 14.3ml/cmH₂O in average, respectively, and was not related to severity of incontinence. The statistical significant differences between continence or mild incontonence patients and moderate or severe incontinence patients were found for the mean functional profile length (2.04 versus 1.37cm, respectively; p<0.05) and maximum urethral closure pressure (42.3 versus 17.3cmH₂O, respectively; p<0.05). But some patients with continence or mild incontinence demonstrated low values in either parameters. No statistical difference was found between continence and mild incontinence patients. On lateral urethrography, the posterior urethrovesical angle was not correlated with the severity of incontinence. The statistical significant difference between continence or mild incontinence patients and moderate or severe incontinence patients were found for the mean height of the urethrovesical junction from lower edge of the pubic bone (1.2 versus 0.37cm, respectively; p<0.05) and angle between anterior and posterior bladder walls at the bladder neck (75.3° versus 42.7°, respectively; p<0.01). So, bladder neck showed deep wedge-shaped slit in moderate or severe incontinence patients suggesting loss of elasticity of bladder neck or urethra.
From these results, it was concluded that incontinence following total prostatectomy would be reduced by precluding patients with local invasive tumors, preserving the integrity of the membranous urethra and bladder neck and avoiding of excessive dissection around the membranous urethra.

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Flow cytometric DNA analysis was performed in 21 cases of primary hyperparathyroidism (19 adenomas in 19 cases and 5 glands with primary hyperplasia) and 24 glands with secondary hyperplasia. Tissue intact-PTH concentration was measured in another 41 glands with secondary hyperplasia. Glands with adenoma had a higher proliferative index than normal glands or glands with secondary hyperplasia. In the adenoma group, there was a negative correlation between proliferative index and age, an indicator of the tumorous nature of adenomas. Daily urinary calcium excretion in case of adenoma and tissue intact-PHT concentration in glands with secondary hyperplasia also showed correlations with proliferative index, which demonstrates a close relationship between cellular proliferation and endocrine activity. Gland weight and proliferative index had no significant correlation in both groups. Therefore, another mechanism besides cellular proliferation and endocrine activity, such as number of non-functional parathyroid cells, should be considered.

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To establish a quantitative dual-parameter flow cytometry (FCM) analysis of cell surface antigens, possible obstacles caused by contaminated leucocytes in a specimen and staining and measuring conditions were investigated using human bladder cancer cell lines, 5637, T24 and SW1710. The first monoclonal antibody (MoAb) used to select urothelial cells in a specimen was applied with the second MoAb used to discriminate between normal and transformed urothelial cells. MoAbs Due AUT2 and CD45 appeared to be suitable for the selection of urothelial cells, while Due ABC3 and Due ABC5 were applied to detect transformed cells. Tumor cell-leucocyte suspension was simultaneously stained with conbinations of these MoAbs. The results demonstrated that Due AUT2 and CD45 effectively eliminated contaminated leucocytes by means of positive and negative selection of the urothelial cells, respectively. Based on these experiments, dual-parameter FCM analyses of bladder washing from 5 patients with bladder cancer were performed using MoAbs Due AUT2 and Due ABC 3. The results indicated that by dual-parameter FCM distinct antigenic features of transitional cells could be investigated even if considerable amounts of contaminated leucocytes were present. The clinical impact of this approach is a subject of ongoing trials.

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Tumor grading protocols in renal cell carcinoma (RCC) have met with only limited success of prognostic value. The increase in argyropholic nucleolar protein (AgNOR) count of a cell has been reported to reflect rDNA transcriptional activity and state of cellular activity. Therefore, the relationship between number of the AgNOR in nucleus and proliferative activity or clinical course in patients with RCC was evaluated. Using 6 cell lines derived from RCC patients and established in our institute, the number of AgNOR and doubling time of the cell were compared. These two values had statistically high negative correlation; a coefficient of correlation was -0.88. The AgNOR values in the cells of RCC (2.22±0.81) in 45 patients were significantly higher than those of normal proximal tubules (1.54±0.21) (p<0.05). And, the numbers were increased with the progress of grades in RCC; 1.70±0.33 in Grade 1, 2.12±0.74 in Grade 2 and 3.19±0.19 in Grade 3. Moreover, the numbers of AgNOR were higher in infiltrating type such as sarcomatoid type or INFγ. However, no significant relation in the AgNORs numbers was observed in subcell type of RCC. The patients with RCC having a counts of 2.5 or more of AgNOR showed a significantly poor prognosis. These results suggest that the determinations of the AgNOR numbers have a value to evaluation of the tumor proliferative activity in RCC patients.

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The major problems in liquid storage of donated blood are the limitation of blood volume preserved and the time consumed.
We studied on the usefulness of utilization of recombinant human erythropoietin (rH-EPO) for preoperative collection of autologous blood. Patients were devided into 2 groups: Group 1 (12 patients) received 3000 unit of rH-EPO intravenosly every day. Group 2 (10 patients) was not treated with rH-EPO.
All the patients were given ferrons sulfate 100mg of iron orally every day. As a rule, 400ml blood was donated two or three times a week for rH-EPO treated group, while, for control group 400ml blood was collected once a week. Some patients did not donate 400ml because of their critical condition.
The blood volume preserved became 780.9±284.1ml in Group 1, and 910.8±263.9ml in Group 2. However, the number of days until operation were significantly shorter in Group 1 (8.7±3.6 days) than in Group 2 (26.2±11.2 days). Hemoglobin and Hematocrit levels recovered promptly in rH-EPO treated group.
In control group, 2 patients complained of nausea and vomiting caused by severe anemia. On the other hand, no one with rH-EPO therapy did not show any side effects and complications.
Our study indicates that the administration of rH-EPO enables us to collect an adequate volume of autologous blood preoperatively in a shorter period of time.

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Of 71 patients who underwent ultrasound guided transrectal needle biopsy at the urology clinic in Kitasato University Hospital 19 (26.8%) patients were found to have prostate cancer. The positive predictive value for transrectal ultrasonography (hypoechoic lesion) was disappointing-only 30% (18/60). While hypoechogenicity has been increasingly accepted as the most sensitive ultrasonographic indicator of malignancy, the specificity of hypoechogenicity is related to benign structures that may also appear hypoechoic. Sonographic detection of prostate cancer is also confounded by the presence of iso- and hyperechoic tumors. Experienced sonographer should be alert to this limitation of the current technology of transrectal ultrasound.
The advent of the Biopty gun enabled us to take multiple biopsy cores easily and quickly. Liberal use of random systematic biopsy in addition to directed cores from a hypoechoic lesion should enhance the detection of prostate cancer regardless of the tumor echogenicity.

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An experimental reconstruction of the urinary bladder using specially designed bovine cross linked atelocollagen sponge was performed after partial cystectomy in 12 male rabbits. Bladder reconstruction with hybrid type biomaterials using both atelocollage sponge and cultured autologous cells were performed in 5 rabbits (the 1st group). The autologous cells were collected from the mucosa and muscular layer of the urinary bladder and were seeded on the atelocollagen sponge before reconstruction. Reconstruction using atelocollagen sponge without autologous cells were performed in the other 7 rabbits (the 2nd group). In 9 of these 12 rabbits, atelocollagen sponge was successfully implanted in the native urinary bladder. Histopathological findings revealed that seeded autologous cells and growth of surrounding host cells could be seen similarly in the atelocollagen sponge but these could not be differentiated by these could not be differentiated by routine histopathological techniques. In conclusion, these results showed a possibility of construction of artificial urinary tract using both atelocollagen sponge and autologous cells.

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In this report, we demonstrated that Interleukin-6 (IL-6) production could be induced by stimulating renal cell carcinoma cell lines, namely ACHN, Caki-1 and TC-1 cells with Interleukin-1β (IL-1β). IL-1β had no effects on cell proliferation in ACHN cells. However, IL-1β could suppress cell proliferation in Caki-1 and TC-1 cells. Flow cytometric cell cycle analysis by double staining method with propidium iodide and Proliferating cell nuclear antigen (PCNA) disclosed IL-1β caused cell accumulation at G1 phase.
Fine granules were visualized in perinuclear area of TC-1 cells treated with IL-1β under microscopy. High electron density granules and spherically dilated rough endoplasmic reticula were observed by electron microscopic examinations. In TC-1 cell culture, IL-1β excretion into the supernatant was demonstrated by bioassay and ELISA.
These results suggest that IL-1β functions as an “autocrine growth inhibitor” against TC-1 cells. Half-maximal inhibition of IL-1β and IFN-α was 6.5pg/ml, and 720U/ml, respectively for TC-1 proliferation and combination of these cytokines showed enhanced activity in cell growth inhibition.

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Several methods to provoke ejaculations artificially have been used to treat patients with anejaculation. The purpose of this study is to investigate the clinical usefulness of electroejaculation for patients with anejaculation induced by spinal cord injury or surgical operation. Forty patients with spinal cord injury and one with anejaculatin after radical operation for rectal cancer underwent electroejaculation by Brindley's technique and/or modified Seager's technique. To reduce the electric energy consumed in patients, we applied bipolar pulses for modified Seager's technique instead of sine-wave current. Seminal emissions were obtained from 11 out of 18 patients by Brindley's technique and from 24 out of 29 patients by Seager's technique. From the patient with anejaculation after radical operation for rectal cancer, semen was obtained by modified Seager's technique.
Most common complications were autonomic dysreflexia and pain. Since these complications disappeared soon after the termination of electrostimulation, this method was thought to be safer than intrathecal injection of neostigmine.
Regarding the semen quality, it seemed that total sperm counts got worse as the interval after injury was extended. Not only in the chronic stage but also in the first one month after spinal cord injury, sperm motility was low. It was suggested that dysfunction of the testis and epididymis appeared in the early stage of spinal cord injury.

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The effect of human chorionic gonadotropin (HCG) on renin concentration and renin mRNA was studied using the testis and kidney of rats. Forty-five rats were divided into three groups. The first group (25 rats) was used for short time course study with single injection of 150 IU HCG and the second group (10 rats) for long term injection of 150 IU HCG daily for 3 weeks. In both groups, serum and testicular sample were taken after 24 hours both nephrectomy in order to exclude the influence of renal renin and angiotensin. The third group (10 rats) was used to find the effect of HCG on renal renin. Plasma and testicular renin concentration were measured by radioimmunoassay of angiotensin I. The specificity of renin concentration was determined using a specific renin antibody. Renin mRNA of the kidney and testis were measured by a sensitive RNAase protection assay method.
Testicular renin mRNA increased and reached the maximum level at 8hrs after 150 IU HCG single injection. And also testicular renin concentration significantly increased and it showed the maximum levels at day 3. However long term HCG administration in rats showed higher in levels in testicular renin concentration, however renin mRNA level was not increased. Non-nephrectomized rats showed low levels of plasma renin concentration and no changes in mRNA after HCG administration.
The results suggest that renin angiotensin results suggest that renin angiotensin system independently exists in the testis and testicular renin mRNA is increased by HCG administration.

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We experienced a case of retroperationeal fibrosis with formation of a pelvic tumor. The patient was a 55-year-old female who showed right-side hydronephrosis on examination and was admitted to this department for consultation. Retrograde pyelography clearly showed that the hydronephrosis was due to lower ureteral obstraction resulting from a pelvic tumor. Ultrasound, CT and MRI showed a tumor adhering to the right posterior surface of the bladder, and it was thought that the tumor was probably malignant. Transdermal/transvesical needle biopsy and transvaginal needle biopsy showed a minimal invasion and allowed the diagnosis of retroperitoneal fibrosis to be made. Ureterolysis was not carried out, and the patient was treated with steroid monotherapy. She was begun on 30mg of prednisolon, and administration was continued for approximately 3 months while gradually decreasing the dosage. On completion of administration, the intrapelvic tumor had completely disappeared, showing that treatment was markedly effective. The patient had a history of an orbital pseudotumor, and it was concluded that this was a rare case coming under the heading of multifocal fibrosclerosis.

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