In order to determine whether or not α-adrenoceptors are present in adrenal glands, radioligand receptor binding assay was performed in both Sprague-Dawley (SD) rat and human adrenal gland membranes.
Radioligand binding assay using ³H-prazosin as an α₁-adrenoceptor ligand and ³H-yohimbine as an α₂-adrenoceptor ligand, clearly demonstrated alphal and alpha2 receptors present in both rat and human adrenal gland membranes. Maximal binding capacity (Bmax) and dissociation constant (Kd) of ³H-prazosin binding to the rat adrenal gland were 12.5fmol/mg protein, and 0.11nM, respectively. Those for the membrane preparations from adrenal cortex and medulla of the normal human were 16.3fmol/mg protein, 0.34nM and 16.3fmol/mg protein, 0.27nM, respectively. And those of the human pheochromocytoma were 25.6fmol/mg protein, 0.15nM, respectively. On the other hand, Bmax and Kd of ³H-yohimbine binding in the rat adrenal gland to were 22.9fmol/mg protein, and 4.28nM, respectively. Those for the membrane preparations from adrenal cortex and medulla of the normal human were 40.4fmol/mg protein, 5.15nM and 12.2fmol/mg protein, 5.39nM, respectively. And those of the human pheochromocytoma were 35.8fmol/mg protein, and 1.08nM, respectively.
Bmax (35.8fmol/mg protein) of ³H-yohimbine binding in the pheochromocytoma was significantly (p<0.01) greater than that (12.2fmol/mg protein) in the human normal adrenal medulla, while Kd (1.08nM) of this binding in the human pheochromocytoma was significantly (p<0.01) lower than that (5.39nM) in the human normal adrenal medulla. Our data suggest that the alpha2 receptor had greater affinity and binding site density to its agonist in the human pheochromocytoma than in the human normal adrenal medulla.

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Among 670 infertile men, 72 were diagnosed as pyospermia according to our criteria. i. e., WBC≥10/hpf semen. The sperm motile efficiency index (SMEI) which indicates the rate of progerssively motile sperms, was significantly low in pyospermic group compared with that of non-pyospermic men (WBC<5/hpf semen). From the result of split ejaculation, a major cause of pyospermia was supposed to be chronic prostatitis.
The SMEI was decreased immediately after addition of the neutrofils and granulocyte elastase to semen. The mean value of granulocyte elastase in pyospermic group was 2859.6μg/L, whereas that of non-pyospermic men was 131.6μg/L.
In summary, granulocyte elastse in seminal plasma may be a cause of inhibition of sperm motility in pyospermic state.

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During the 4 year peirod from September 1, 1984 through August 31, 1988, a total of 1, 866 patients with calui of the urinary tract (125 patients had bilateral calculi) were subjected to extracorporeal shock wave lithotripsy (ESWL) with a DORNIER HM3 ESWL apparatus. Follow-up was performed factor 1, 056 cases 3 or more months after complete elimination of the calculi, and data were obtained for 343 of them. Lithiasis was found to have recurred after ESWL in 30 cases, with a recurrence rate of 11.1%.
Recurrence was seen in 16.9% of cases with multiple calculi and 6.5% of cases with a single calculus. The difference wa statistically significant. Surgical removed of calculi or spotaneous discharge of calculi had been experienced in 50.0% of the reccurent cases and 27.8% of the non recurrent cases. The difference was also statistically significant. Stone size, stone location and urinary tract infection were unrelated to the recurrence.

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The viability of preserved kidney is considered to be evaluated by mitochondrial function. We used the three experimental conditions of WIT 60 minutes (group I), 90 minutes (group II), and 120 minutes (group III) using rabbit. We measured the ATP value of renal tissue as a direct method before ischemia (control), immediately before recirculation, and at one hour, two hours, one day, two days, four days and seven days after recirculation, using isotachophoresis (Tachophor LKB 2127), and as an indirect method, serum pyruvic acid, lactic acid and LDH values were measured simultaneously. The ATP value in groups I, II, and III before recirculation were 1/10 lower than controls. However, as WIT became longer, the recovery speed was diminished. The serum P/L ratio reflected the mitochondrial function in group III. (p<0.05) The measurement of ATP value by this method, although it is somewhat invasive, is a useful method with a simple technique and a short analysis time. The serum P/L ratio is considered not to reflect the mitochondrial function directly, but can be measured adequately in WIT 120 minutes.

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A normal rat bladder transitional epithelial cell line and seven tumor cell lines cultured from tumor induced by 0.05% N-Butyl-N-4-hydroxybutyl-Nitrosamine (BBN) were established and a comparative study on the doubling time and Ultrastructure of the cultured cell lines was performed.
1. Seven cultured cell lines (TU-B1 1-7) were obtained from bladder tumors induced by the administration of BBN for 32 weeks.
2. The doubling time of the cultured tumor cell lines were 43, 24, 28, 24, 25, 31, and 45 hours, suspectively.
3. These cultured tumor cell line were inoculated subcutaneously into nude mice and transitional epithelial carcinomas differing in degree of differentiation were observed.
4. Horizontal and tangential sections of these cultured tumor cell lines were examined by transmission electon microscopy. The development of intracellular organella and the presence of microvilli on the surface of the cells were noted. Intracellular adheision was poor but the morphological characteristics of bladder transitional epithelium with compressed vesicles and other intracellular structures such as desmosome and free ribsomes were observed.
5. By applying the attached collagen gel method to our cell lines, it was possible to obtain cultured rat epithelial cells with the same morphology as in vivo, in addition to the tumor cell lines.
6. These cultured cell lines of normal rat transitional epithelium appear to be ueful a experimental models with which one could clarify the function of the transitional epithelium and the mechanisms of bladder carcinogenesis.

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Blood group antigens (BGA) were stained by PAP methods and the relation between staining pattern (classified into five types: I, II, IIIa, IIIb and IV) and tumor prognosis was examined in 54 patients with primary superficial bladder tumor. The recurrence rate was significantly higher in BGA negative (Type IIIb or IV) or Type IIIa cases than in antigen positive (Type I or II) cases. Stage-up was observed only in BGA negative cases. Although staining pattern of recurrent tumor differed from that of primary tumor in some cases, it is believed that prediction of malignant potential should be performed at the primary development, when tumor has not been influenced by treatments. With regard to the relation between staining pattern and tumor prognosis, no significant difference was found between the cases of A, B and AB blood groups and those of O group.

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We investigated retrospectively tumor factors such as tumor organ, method of tumor collection, tumor morphology and grade, concerned with primary cultures of transitional cell carcinomas of bladder, renal pelvis and ureter. Moreover, we investigated whether chemotherapy before tumor collection influence on the success rate of primary culture.
After mechanical disaggregation of specimens from 42 bladder cancers and 11 renal pelvic or ureter cancers, monolayer cultures were carried out. When epithelial growth or colony-formation was observed, we determined that primary culture was succeeded.
In total 30 primary cultures out of 53 (56.6%) were successful and tumor organ or method of tumor collection did not influence primary cultures. The success rates in the groups of papillary tumors and non-papillary tumors were significantly different (72.4% and 37.4%, respectively). Culture was more successful with grade 1 tumors. Although intravesical chemotherapy before tumor collection did not influence the success rate of primary culture, one-shot intra-arterial infusion chemotherapy made it worse (p<0.05) and it was concerned with histopathological effects according to the classification of Shimosato and Oboshi.

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We invented a new parameter of uroflowmetry and decided its normal range. In this study, 153 normal and 60 obstructive urinary flow curves were analysed. Of 153 normal curves, 70 were obtained from 28 young males and 83 from 78 BPH (benign prostatic hyperplasia) patients after operation. 60 obstructive curves were obtained from 55 BPH patients before operation.
Presuming that the lower limit curve of the flow rate nomogram by Shiroky was logarithmic, natural logarithmic values of voided volume (Ln (v. v.)) were plotted against average flow rates (Qmean). Thus we could draw a strainght line between normal group and obstructive one. This line was represented as Y=1.81(X-2.2). Next, seeking the inclination of the line which linked the point of any micturition with (2.2, 0), micturition coefficient was calculated by Qmean/(Ln (v. v.)-2.2). We thought that the normal range of uroflowmetry could be decided by its inclination. The normal range was more than 1.84 and the boundary range was 1.81-1.84.

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We suspect a difference between the effective rate of human tumor clonogenic assay (HTCA) and that of clinical chemotherapy against renal cell carcinoma. We investigated the sensitivity of ACHN, the cell line of renal cell carcinoma, and its colony forming cells (dividing cells) obtained on double soft agar against vincristine sulphate (VCR). In addition, PC-3, a cell line of prostatic carcinoma, and HeLa, cell line of cervicar carcinoma, were investigated. We obtained the results that each colony forming cells had higher sensitivity than each parent cells against VCR in the growth activities and the DNA synthesis measured by the uptake of ³H-thymidine. Because the cells targeted by HTCA are dividing cells, they are oversensitive compared with the true sensitivity of tumors.

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The long term results of 28 HLA 1-haploidentical donor kidney transplant recipients recieving preoperative lymphocyte deletion through thoracic duct drainage and low dose of steroid and azathioprine immunosuppressive treatment were presented. The number of removed lymphocytes was 129.9±38.1×10⁹ (mean±SD) and the duration of thoracic duct drainage pretreatment was 35±4 days. Graft survival was 96% at 3 months through 2 years, 89% at 3 years and 84% at 5 years. Patient survival was 100% at 3 months through 2 years and 96% at 3 years through 5 years. Fifteen acute rejection crises were observed in 13 patients within the first 3 months postoperatively. There was no irreversible rejection in the first 3 months. Four chronic rejections were observed in 4 patients. Life-threatening infectious disease was observed in 5 patients, diabetes mellitus in 2 and cataract in 4. These results indicated that the reduction of the dose of steroid in post transplant period might have beneficial effects on the long term graft survival of HLA 1-haploidentical kidney transplant patients receiving TDD pretreatment and the conventional immunosuppressive treatment.

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The results of 20 HLA 1-haploidentical donor kidney transplant patients treated with preoperative lymphocyte deletion through thoracic duct drainage and low dose of cyclosporine and steroid immunosuppressive therapy, were presented. The number of removed lymphocytes was 114±36×10⁹ (mean±SD) and the duration of thoracic duct damage was 35±7 days. Graft survival was 100% at 3-9 months and 89% at 1-2 years after transplantation. Patient survival was 100% at 3-9 months and 89% at 1-2 years. A patient died from lung cancer (adenocarcinoma) in the 9th posttransplant month. Acute rejection was not seen in 20 patients during the first 3 months. Life-threatening infectious disease was never seen either. Diabetes mellitus was observed in 1 patient. No other complications were observed. These results indicated that thoracic duct drainage and low dose cyclosporine and steroid postoperative immunosuppressive treatment might yield complete success in HLA 1-haploidentical kidney transplant patients.

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We retrospectively reviewed 32 patients who underwent parathyroidetomy at our hospital for the last fourteen years.
1) Clinical appearance of primary hyperparathyroidism was in younger age in women.2) In previous history or at the time of PTX, 9 patients had malignant tumors including 6 thyroid cancers, 36% of the patients with out bone related symptoms had a remarkable decrease in bone mineral content.
3) After PTX, none of patients had recurrent urolithiasis and bone mineral content of all patients was significantly increased in a short time. In addition, upper GI complaints were improved, or hypertension was partially normalized. However, renal insufficiency remained unchanged.
4) In preoperative localization study, Ultrasound sonography (US) demonstrated the best accurracy rate of 88% when only one gland was involved. US was able to detect multiple gland involvement only in 20% of 5 cases.
5) Hypercalciuria was recognized as one of the risk factors of stone formation in patients with primary hyperparathyroidism.

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In June 1988, the new type of the lithotripter MPL 9000 (Dornier), which was the first interdisciplinary lithotripter for treatment of urinary and biliary calculi, was installed at the Shakai Hoken Chukyo Hospital. MPL 9000 has some features which enable one to treat with low range of shock wave energy and without anesthesia due to the enlarged aperture of the ellipsoid (210mm), and locate the stone by computerized two ultrasound probes (coaxial, lateral). Unlike HM-3, the water bath is not used: shock wave is shot through the water cushion.
From June to November 1988, 35 patients suffering from 64 urinary calculi were treated. The majority represented caliceal (75%) and pelvic (17%) stones, whereas 5 calculi were treated in the upper and lower ureter. Twenty-four patients were treated in one ession and 11 patients needed additional sessions. The given number of shock waves was between 1337 and 3050 per one ession and averaged 2403 with low generator voltage (15-18kv). Twenty sessions (42%) were given without any medication and other 28 sessions (58%) were under analgesia (Pentazocine, i. v.) for the pain complained during the treatment.
The rate of successful disintegration (less than 5mm) was 88%. After the 1-month followup, 47.1% were free of stone, and 62.1% were free after the 3-month. Four patients had arrhythmia and one patient was with a subcapsural renal hematoma.
We have concluded that this lithotripter is useful to treat upper and lower urinary tract calculi, in particular radiolucent ones in high risk patients because it is applicable without anesthesia.

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Bladder and urethral functions were evaluated urodynamically in 62 patients with cervical cord compression disorder caused by either ossification of the posterior longitudinal ligament of the cervical spine (32 patients), cervical spondylosis (14 patients), prolapsed cervical intervertebral disc (14 patients) or cervical spinal canal stenosis (2 patients). The patients included 46 males and 16 females with average age of 57 years (range 39 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination.
Cystometry revealed preoperative neurogenic bladder in 22 patients (35%) including overactive detrusor in 10 patients (45%) and underactive in 6 (27%). Twenty-one of them underwent electromyographic examination of external sphincter and 14 (67%) had overactive sphincter. Bladder and urethral functions appeared to be impaired in association with myelopathy of the pyramidal and spinothalamic tract of the cervical cord, because of high incidence of neurogenic bladder associated with positive Babinski's reflex and sensory disturbance at the perineal and lower extremity area. Furthermore, since many patients with deep sensory disturbance in the lower extremities had underactive detrusor, it appears likely that underactive detrusor was accompanied with myelopathy in the posterior funiculus of the cervical cord which mediates bladder proprioceptive sensation.
Of twenty-two neurogenic bladder patients, seventeen underwent a cervical bone operation and eleven received postoperative urodynamic evaluation. The average interval from the operation to urodynamic evaluation was 1.6 months (range 1.1 to 2.3 months). Over half of the patients were found to be improved urodynamically as well as neurologically. No marked postoperative improvement of bladder and urethral functions was achieved during the present short term observation in one patient who had long-term preoperative dysuria and in another without postoperative neurologial improvement.

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Therapy with proton beam is superior to that with photon beam in concentrating the dose within a lesion. Fifteen patients with urinary malignant tumors were treated by proton irradiation during the period from June, 1985 to March, 1989 at Particle Radiation Medical Center, University of Tsukuba. Four patients were with renal cell carcinoma, five with prostatic cancer and six with bladder cancer. Treatment results were assesed by change in tumor size either three or six months after the irradiation. In all the four cases with renal cell carcinoma, the tumor sizes were found to be unchanged without any enlargement. Of the five cases with prostatic cancer, two showed that the treatment was effective and the tumor sizes in the other three cases were found to be unchanged. In three of the six cases with bladder cancer the tumors disappeared while the treatment was found effective in two other and it did not cause any enlargement of the tumor in the remaining one. Although local control of the tumor was succesful in all the cases, one patient with prostatic cancer and three with bladder cancer died of cancer. Various side effects, such as radiation cystitis, were observed. This prospective therapy is expected to replace the conventional photon therapy. However, some improvement is needed to make full use of the advantageous properties in dose distribution. Combination therapy with other general therapy is required for some cases.

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In 244 cases treated by subcapsular prostatectomy during the period from April 1975 to December 1985, whole tissue specimens were prepared by a step section technique to examine them histopathologically in accordance with the handling agreement for prostatic cancer presented by the Urologic Society of Japan. The degree of differentiation, clinical stage of hte disease, the size of the lesion and the distance to the margin were determined. Incidental carcinoma was found in 35 cases (14.3%), which increased with age.
There were 21 cases of stage A₁ and 14 cases of A₂. Diffuse proliferation was found in 4 cases. Isolate dcarcinomatous focus was observed in 40 sites, and well, moderately, and poorly defferentiated adenocarcinoma in 33, 3 and 4 sites respectively. The maximum diameter of cancer wa below 5mm in 80%, while the distance from the center of the carcinomatous focus to the surgical margin was within 3.5mm in 905. Seven cases had plural lesions.
These lines of evidence mentioned above may support carcinogenesis from the subcapsular region as well as multicentric origin of cancer.

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Interferon-alpha (IFN-α) producing capacity was measured in 47 patients with prostatic cancer by whole blood assay. The mean IFN-α producing capacity of prostatic cancer patients was 3657IU/ml, which indicated a significantly (p<0.005) lower value than that in healthy male aged 50 years or more.
IFN-α producing capacity in patients with Stage D disease was lower than that with Stage A, B or C. The higher the grade of the disease, the lower tended to be the capacity. A certain relationship was suspected between IFN-α producing capacity and the prognosis of each patient. In particular, in patients with prostatic cancer in Stage D, the prognosis was worse in low IFN-α producing capacity group (<3000IU/ml) than in normal or high IFN-α producing capacity group (≥3000IU/ml). It was considered that IFN-α producing capacity might be useful in developing the prognosis of patients with prostatic cancer.

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Ureteropelvic junctions surgically taken from twelve patients with congenital hydronephrosis were submitted to stereomorphometric studies on the architectural changes of smooth muscle layer. The specimens were opened longitudinally along the ureteral axis, flatly extended on a board, fixed in formalin and embedded in celloidin-paraffin. Serial histological sections in parallel with the wall were prepared; the 3D muscular architecture, visualized in some cases by computer-aided reconstruction, was simplified into vectors of bundles so that their arrangement might be expressed by a vector distribution. Deviation from the norm of architecture at the ureteropelvic junction was disclosed: Reduced muscles with increased connective tissues in four cases and disarrangement of bundles in eight cases, including two with predominantly longitudinal element, three with circular element and another three with irregular orientation. These abnormalities, probably reflecting abnormal maturation of muscles, appear to be related with the urinary obstruction in patients with congenital hydronephrosis.

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In order to evaluate the nephrotoxicity by antibiotics, effects of these agents were investigated in terms of protein synthesis and nucleic acid metabolism in the kidneys of Wistar rats. Aminoglycoside antibiotics (streptomycin, kanamycin, gentamycin), tetracycline (doxytetracycline), chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used. These antibiotics were given to the rats for 5 successive days. On the 6th day ¹⁴C-6-orotic acid and ¹⁴C-1-leucine were administered intraperitoneally.
Incorporation rates of these tracers into ribonucleic acid and protein fraction in rat kidney ribosomes (polysomes) were measured. Another experiment was undertaken in vitro by separating the polysome fraction from the rat kidneys. In vitro acellular protein synthesis using these polysomes was established. Effects of antibiotics on the incorporation rates of ¹⁴C-1-leucine were examined. Marked reduction of incorporation of these tracers into nucleic acid and protein in vivo and in vitro was induced by aminoglycoside antibiotics. These facts suggest that aminoglycoside antibiotics develop nephrotoxicity by interfering with the metabolism of ribosomal RNA and protein.

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In order to assess the potential nephrotoxicity of antibiotics, effects of these agents on rat kidney lysosomal membrane were investigated in various conditions. Antibiotics were given to Wistar rats for 5 successive days. After nephrectomy rat lysosomes were separated and their membrane stability was examined by measuring the activities of acid-phosphatase. In addition, after separation of lysosomes from normal untreated Wistar rats, antibiotics were added in the incubation system to assess the in vitro effect of antibiotics. Effects of renal ischemia and the lysosomal membrane stabilizer (cortisol) were also examined.
Aminoglycosides antibiotics (streptomycin, kanamycin, gentamycin), doxytetracycline, chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used for this purpose
It was clearly pointed out that aminoglycosides intrefered with the lysosomal stability in vivo and in vitro.
After a 60 minutes ischemia of the rat kidneys by clamping the renal arteries, effects of antibiotics on administration of 5 successive days on rat lysosomal stability were investigated. It was demonstrated that aminoglycosides also made the lysosomal membrane more unstable.
Effects of the lysosomal stabilizer, cortisol, on rat kidney lysosomes were examined. Use of cortisol simultaneously with an antibiotic was more effective than that before and after it.

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Extraction of glycolipid component from hypertrophic and cancerous prostatic tissue were performed using chroloform-methanol solution and isopropanol-hexan-solution. The extract was separated into the “upper phase” and “lower phase” by Folchs fractionation technic. Each fraction was conjugated with acid treated salmonella minesota and than it was injected subcutaneusly, intra-peritonealy and finally intravenously to BALB/c mice. Spleen cells from immunized mice were fused with P3X63, and antibody APG1 was obtained. APG1 shows a preferential reactivity towards prostatic tissue by the immunihistochemical analysis. Furthermore, the immunohistochemical analysis using enzyme and acid treated tissue and TLC immunostaining indicate that this monoclonal antibody specifically recognizes the sialylglycochain expressed in the prostatic tissue.

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We studied the efficacy and safety of recombinant interleukin-2 (rIL-2: S-6820) for the treatment of renal cell carcinoma as well as the effect of blood transfusion upon the immune response of these patients.
Among 14 cases of renal cell carcinoma treated by i. v. infusion of rIL-2, a partial response (PR) was achieved in one patient, 10 patients had no change, and in 3 had the disease progressed. The overall efficacy rate was 7.1%. However, the rate increased to 12.5% in cases with pulmonary metastases and to 14.3% in cases without any blood transfusion within a year before treatment with rIL-2. No severe side effects were observed, except for central nervous system distarbance in one case. During the rIL-2 therapy, LAK activity was suppressed in the transfused patients. On the other hand, NK activity was augmented in transfused patients to the same degree as in non-transfued cases. No significant changes of lymphocyte count and the subsets of peripheral blood lymphocytes were observed in either group treated with rIL-2. Anemia and radical nephrectomy did not affect the immune response in these patient. Thus, it appeared that blood transfusion altered the immune response in patients treated with rIL-2. However, it could not be concluded that transfusion definitely had an adverse effect on the clinical efficacy of rIL-2 for renal cell carcinoma.

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The association of angiomyolipoma with renal cell carcinoma in tuberous sclerosis is extremely rare, although the relation between tuberous sclerosis and angiomyolipoma of the kidney is widely recognized. We report here a case of bilateral angiomyolipoma and renal cell carcinoma of the right kindey with tuberous sclerosis and demonstrate the diagnostic difficulties in distinguishing between these tumors.

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Recent understanding of the pathogenesity of haemorrhagic tendency as well as advance of management of patients with this disease makes its surgical treatment possible. Since 1979 we have experienced three male patients with haemorrhagic tendency.
The first case was a bladder carcinoma with hemophilia A. He had been given 2500 unit of Conco-eight^® (coagulation factor VIII) before transurethral resection of bladder tumor (TUR-Bt) and was given 1000 unit of Conco-eight^® every eight to twelve hours for seven days postoperatively. The second case was a bladder carcinoma with von Willbrand disease. This case was also pretreated by Conco-eight^® before operation and we had difficulty in controling his coagulopathy for one month postoperatively. The third case was a benign prostatic hypertophy with idiopathic thrombocytopenic purpura (ITP). He had been given a huge dose of gamma globulin for six days before operation and on the operation day his platelet count was normalized. Since his prostate was estimated to weight over 70g, suprapubic prostatectomy was selected.
All these three cases were operated uneventifully. From this experience we believe that with proper preoperative and postoperative management, patients with haemorrhagic tendency can be operated safely.

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