Effect of Cyclosporin A on human lymphocyte responses and antibody production in rats were studied. MLC was performed by responder cells cocultured with mitomycin treated stimulator cells for five days. Twenty hours before harvesting, ³H-TdR was added. Mitogenic stimulation of lymphocytes was performed in the same procedure. CML was assayed by incubating cells from macro-MLC for four hours with PHA stimulated cells labeled with ⁵¹Cr (E/T=50/1).
Cyclosporin A showed dose-dependent inhibition of lymphocyte blastogenesis in primary and secondary MLC and mitogenic stimulation. CML assay showed that cyclosporin A inhibited the generation of cytotoxic lymphocytes. Lymphocytes harvested from MLC with cyclosporin A showed suppressive effect of CML when these lymphocytes were added to the effector phase. It may indicate the presence of suppressor cells.
Cyclosporin A inhibited antibody production in rats. Though cyclosporin A was administered only for the first seven days, after reimmunization at three weeks, antibody production was inhibited to the same degree. It is considered that cyclosporin A is important at the early stage of antigenic stimulation or some immunological tolerance may be induced.
It is accepted that allogenic MLC or Con A stimulation of lymphocytes induce suppressor T cells. Con A induced suppressor T cells have an ability to form rosette with autologous erythrocytes. In the allogenic MLC with or without cyclosporin A, the number of autorosetting cells increased, which had a suppressive effect on MLC. Cyclosporin A is considered to have no inhibitory effect on the generation of suppressor T cells.
In allogenic MLC with cyclosporin A, macrophage-like adherent cells, which suppressed MLC, increased in number. Generation of macrophage-like cells may be one of the immunosuppressive mechanisms of cyclosporin A.

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Immunosuppressive mechanism of cyclosporin A (CsA) was studied using human lymphocytes in vitro. MLC was performed by responder cells cultured together with mitomycin treated stimulator cells for five days. Twenty hours before harvesting, ³H-TdR was added and its uptake was counted. CML was assayed by incubating effector cells from MLC for four hours with 3-day-old PHA stimulated target cells labeled with ⁵¹Cr (E/T=50/1).
A delay in adding CsA to the allogenic MLC resulted in a progressive increase of ³H-TdR uptake and when added over 48 hours after the beginning of MLC, inhibition rate was low. On the contrary, removing CsA from the culture after 24 hours showed relatively strong inhibition. These results suggest that CsA acts at an early stage of lymphocyte stimulation. Although MLC performed in the absence of CsA resulted in the generation of specific cytotoxic effector cells, when CsA was added in the effector phase, it had no inhibitory effect on the action of cytotoxic T lymphocytes.
CsA was assessed for its effect on the production of interleukin 2 (IL 2) and the acquisition of responsiveness to IL 2. Supernatants from the CsA-treated MLC showed a dose-dependent decrease in the ability to support the proliferation of Con A stimulated lymphocytes, indicating the inhibitory effect of CsA on the production of IL 2. CsA showed a dose-dependent inhibition of MLC, but this inhibitory effect could not be reversed completely when exogenous IL 2 was added to the culture. When lymphocytes were stimulated by IL 2 after preincubation with Con A and/or CsA, proliferative activity of lymphocytes was reduced in the presence of CsA during the preincubation.
From the above results, it is concluded that CsA inhibits T cell activation both by blocking IL 2 production as well as by inhibiting the induction of IL 2 responsiveness.

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Anticancer drug, styrene maleic acid neocarzinostatin (SMANCS) or mitomycin C (MMC) dissolved in the lipid lymphographic agent, Lipiodol (SMANCS/LPD or MMC/LPD) was administered via renal artery in 2 patients with malignant renal tumor.
Lipiodol was observed to remain selectively in the tumor tissue for the longer time.
In the first case treated with 0.25mg SMANCS/LPD per area of the maximum cut surface of the tumor (cm²), the most part of the tumor was necrotic. In the second case treated with 0.185mg MMC/LPD per area of the maximum cut surface of the tumor (cm²), one third of the tumor was necrotic. These results suggest that this therapy may be useful for the malignant renal tumor.
As for the side effects of this treatment, only fever was noted, while gastrointestinal disturbance or bone marrow suppression was not observed.

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Immunosuppressive acidic protein (IAP) levels were measured in 31 patients with testicular cancers and 77 healthy males as controls.
The mean value of serum IAP in patients with testicular cancer (699±337μg/ml) was statistically higher than those of healthy males (396±86μg/ml) (p<0.001). Elevated serum IAP levels were found in 17 of the 31 patients (54.8%).
As to stages, the mean value of serum IAP in stage II and stage III patients (743±258μg/ml and 980±366μg/ml) was statistically higher than those of stage I (425±110μg/ml) and controls (p<0.001) and there were no significant statistical differences in the ralues between stage I and controls.
Then, there were clear relationship between the IAP levels and the stage of the disease.

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Based on ultrastructural findings of transurethral biopsy specimens of tumors of the urinary bladder on preoperative assessment, the scoring of each finding and its summation provided for classification and it was compared with that by light microscopy and evaluated from a view of clinical behaviour of the tumors.
Twenty-eight tumors which consisted of 14 with clinically benign behavior and 14 with clinically malignant course with recurrence, metastasis or fatal outcome due to the disease were evaluated.
The following ultrastructural findings were numerically scored to denote morphological significance in classification; 1) structural atypism, 2) change of basal membrane, 3) differentiating features to adenocarcinoma or squamous cell carcinoma, 4) amount of intracytoplasmic organelles, 5) quantity or quality of mitochondria, and 6) features of nucleolus.
The tumors were categorized into the following three groups: EM group I, II and III.
EM group I: Tumor cells in spindle shape were arranged regularly, intercellular space was wide and each cell was attached by microvilli. The basement membrane was distinct and multilamellar in some cells. Intracytoplasmic organelles were poorly developed, nuclear atypism was slight in degree and the majority of tumor cells had one nucleole in the apparent shape of nucleolonema. Lysosomal granules were mostly distributed in tumor cells in the outer layer and glycogen granules were observed in the whole layer of some of tumor cells.
EM group III: Tumor cells lost their polarity. The cells were in oval or polygonal in shape and were packed tightly. The basement membrane was partly indistinct and connective tissue was frequently invaded. The mitochondria, intracytoplasmic organelles and vacuoles were well developed and increased in number. The nucleus showed high atypism in some cells and did simple immaturity in another cells. An considerable amount of findings suggesting differentiating features to adenocarcinoma or squamous cell carcinoma were observed. Microtubules and tonofibrils which are unidentifiable by light microscopy were well developed.
EM group II: The findings in this category were intermediate between those in EM group I and III.
Clinically benign tumors contained 6 in EM group I, 5 in EM group II, and 3 in EM group III. Clinically malignant counterparts were all categorized in EM group III. The ultrastructural findings in EM group III show morphological characteristics in the tumors with clinically malignant course.

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We compared the results of sterile indwelling catheterization and non-sterile indwelling catheterization which were done in their acute phase of 111 traumatic cervical cord injury patients whom we had followed-up over 2 years since 1965. Fifty-one of 55 patients (92.7%) with sterile indwelling catheter and 43 of 56 patients (76.8%) with non-sterile indwelling catheter were made catheter free within 3 months. There was a tendency that the patients with sterile indwelling catheter had shorter periods of indwelling catheterization. There was no statistical difference in the incidence of urinary tract complications such as epididymitis, urolithiasis and vesicoureteral reflux between the two methods. The patients with sterile method had statistically lower rates of urinary tract infection shown by recent urinary cultures (p<0.05).
Nine patients expired during the follow-up periods. Only one patient with sterile method expired with lung cancer. Eight patients with non-sterile method expired, two of gastric bleeding, two cerebral hemorrhage, one septicemia, one suicide, one pneumonia ans one rectal cancer. The causes of death in 6 patients could be attributed to the failure of urinary managements, because 4 patients had autonomic hyperreflexia, one patient had periurethral abscess resulting in septicemia and one patient committed suicide due to emotional upset for his vesicocutaneostomy by Lapides' method. None of our cases had disturbance of renal functions during the follow-up periods.
The above results indicate the superiority of sterile indwelling catheterization over non-sterile one for the urinary management of traumatic spinal cord injury patients.

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We report on the successful xenotrasplantation of renal cell carcinoma to nude mice (BALE/c-nu/nu, male) and investigated basic characteristics concerning with three established transferable renal cell carcinomas.
Tumor specimens were obtained by surgery, and were inoculated subcutaneously into the nude mouse. Successful transplantation has been attained in 3 out of 13 (23.1%) operated clinical cases, and serially transferable renal cell carcinomas were maintained in nude mice as solid tumors under SPF condition. These three trasplantable tumors (JRC1, JRC9, JRC11) grew locally and the growth rate of the three different tumors varied considerably but the individual tumor had a constant growth pattern even after 10th to 11th passage in nude reciepients.
All three transferable renal cell carcinomas were mainly high grade histologically, and close similarity of histological grade were observed in the part of the original renal cell carcinoma. These three transferable tumors were maintained the same histological appearance during serial passage.
The growth rate of JRC1 was slowest among the three strains, and the body weight was stationary despite the growth of tumors. On the contrary, the weight of JRC9 and JRC11 strains diminished along with the growth of tumors, and four to five weeks after transplantation, they died with anorexic appearance.

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A study was conducted to evaluate the chemotherapeutic effects of anticancer drugs against a human renal cell carcinoma obtained from Jikei University Hospital and serially passaged in nude mice.
Four chemotherapeutic agents that have shown some degree of activity against human renal cell carcinoma in the clinic and therefore were evaluated in this study were adriamycin (ADM), vinblastine (VBL), VP-16 and 5-fluorouracil (5-FU). Comparisons of the effect were made among groups of mice or nude mice given LD₅₀, 1/2LD₅₀ and 1/4LD₅₀ doses.
In order to evaluate the effects of anticancer agents, statistical and histopathological evaluation were made. The two-dimensional tumor measurements taken periodically were transformed into estimates of tumor weights using the formula.
Histopathological changes of treated mice bearing renal cell carcinoma were estimated by the histopathological degenalations which have been proposed by National Cancer Research Institute (Shimosato's classification). Histopathological criteria for evaluation of therapeutic effects were classified into grades I to IV.
Significant effects of single agent therapy based on statistical evaluation were obtained with ADM (1/2LD₅₀) and VBL (LD₅₀) against JRC11 strains, and also were obtained with 5-FU (1/4LD₅₀) against JRC9 and JRC11 strains. Significant effects of combination chemotherapy based on statistical evaluation were obtained with VBL (1/4LD₅₀) and 5-FU (1/4LD₅₀) against JRC9 and JRC11 strains. But significant effects based on histopathological evaluation were only obtained with VBL (1/4LD₅₀) and 5-FU (1/4LD₅₀) against JRC11 strains. And other strains which showed significant effects based on statistical evaluation disclosed hardly any histopathological chainges.
The results suggested that there was no correlation between the results obtained by statistical evaluation and those by histopathological evaluation.

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For the purpose of studying the pathogenesis of the vesicoureteral reflux (VUR), transurethral ultrasonography was done in both normal persons and patients with VUR.
Ultrasonographic studies revealed that the intramucosal ureter was closed except at the time of efflux in normal persons, but the ureteral roof was short and the ureteral orifice was always open in paraplegic patients with VUR.
No changes of the ureteral orifice were recognized at the time of administration of 20μg noradrenaline. It is therefore suggested that, at least in normal persons, the role of the sympathetic system is not so important.

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The late results on 100 patients who underwent urinary diversion at the Department of Urology, Jichi Medical School during the period of 1974 through 1983 were reviewed. The ages ranged from 4 to 84 years old, with sex ratio (M/F) 3.5 to 1. Bladder tumor was the indication of the operation in 76 cases, uterine cancer in 6, urethral cancer in 4, prostatic cancer in 3, the other malignancies in 3 and benign disease in 8.
Cystostomy was performed in 8 cases, nephrostomy in 7, intubated ureterocutaneostomy in 56, ileal conduit in 9 and uretrosigmoidostomy in 20 as the method of urinary diversion.
The relative 5-year survival rate was 51.2% as a whole. That of patients who underwent total cystectomy for bladder transitional cell cancer was 58.2%.
In the cases who underwent total cystectomy and urinary diversion, the postoperative mortality rate was 4.9% (3 cases) and details of postoperative complications were reviewed.

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Forty-six adult patients underwent tubeless cutaneous ureterostomy mainly for advanced intrapelvic malignancies during the 15years since 1969. Construction of nipple stomas was successful in 30 patients (65.2%). Better results were obtained in patients with dilated and non-irradiated ureters. Maintenance of tubeless drainage was possible in 18 patients (60%), while 12 patients (40%) sooner or later required ureteral intubation for stomal stenosis and other reasons. In 7 patients tubeless ureterostomy could be followed for 2 years and 3months to 14years and 8 months with an average of 7 years and 9 months. Urinary drainage and renal function were satisfactory during the period. In 2 patients, however, late obstruction was observed; in one it was caused by gastric cancer metastasis to the ureter 2 years and 3months postoperatively, and in the other stenosis was caused by stomal fibrosis after 10 years of diversion. The results indicate that there are three main changes which affect the stomal patency; 1) atrophy of the ureteral nipple, 2) squamous metaplasia of the ureteral mucosa, and 3) fibrosis of the stoma. Patients with one kidney functioning with a dilated and non-irradiated ureter are good candidates for this kind of operation. However, tubeless cutaneous ureterostomy should be challenged in any of those in whom unilateral ureterostomy is required. Though transureteroureterostomy is a useful procedure in making the stoma single, it should be strictly limited to those in whom construction of a patent stoma is promising.

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A case of spermatocytic seminoma was examined by electron microscopy. Tumor cell size was variable but medium-sized cells dominated. These cells showed several important features as follows: round to oval nuclei with regular margin; prominent nucleoli with dispersed nucleolonema; finely scattered chromatin and occasionally with condensed chromatin in most nuclei; true intercellular bridge, almost identical to those normally seen between germ cells; tubular invagination of nuclear envelope identical to those of typical seminoma; specialized cell junctions of the macula adherens; basal bodies and striated ciliary rootlets.
Compared with a typical seminoma, they have a close resemblance in nuclear aspects, but a true intercellular bridge seems to be peculiar to spermatocytic seminoma.
These ultrastructural findings suggest a germ cell origin of this tumor, but to disclose its more exact origin, i. e., germ cell type, further examination will be needed.

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Human embryonic kidney was examined histochemically using PAP and PAM staining with particular emphasis on the relevance of basement membrane to the formation and development of the nephron.
PAP method was used for staining laminin of basement membrane, and its sensitivity was compared to that of the conventional PAM method.
The results were as follows:
1) In 5 weeks of embryo, laminin of the ureteral bud was already stained in a linear pattern.
2) When renal vesicle was formed from the metanephric blastema, laminin was also noted on the basal aspect, indicating that laminin is intimately involved in the early evolution of cell differentiation from mesenchyme to tubules.
Up to this stage, there was no staining of basement membrane like structure of PAM method.
3) As tubules undergo S-shaped stage and luminar connection of ureteral bud and S-shaped body were noted, laminin was also found to form a continuity from tubules to ureteral bud. At this stage PAM staining became positive from the beginning albeit in a portion of tubules.
4) As nephron matures, staining characteristic of basement membrane by PAP method was changed from a punctate to a linear pattern, and this matched to PAM method for the first time.
These data suggest that (a) basement membrane evolves as nephron is formed from metanephric lastema to tubules and (b) PAP method for laminin is more sensitive than PAM method in assessing the functional role of basement membrane in the development of nephron.

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Muscle fiber types, fast and slow and also white and red, in the male rabbit external urethral sphincter were investigated using two-dimensional electrophoresis of myosin light chains and electron microscopic observation of the sphincter muscle. Myofibrils and the crude myosin were prepared from the sphincter muscle and also from the psoas (predominantly pure fast muscle) and the soleus (predominantly pure slow muscle) muscles as the references. Electrophoretograms showed that the majority of each light chain of myosin from the sphincter muscle was identical to those of myosin from the psoas muscle and only the minority was identical to those of myosin from the soleus muscle.
In the electron microscopic studies, morphological differences were apparent when the sphincter muscle was compared with the psoas (white muscle) and the soleus (red muscle) muscles. The population of mitochondria and the width of the Z-band in muscle fiber cell from the external urethral sphincter were quite similar to those in muscle fiber from the soleus. We have concluded that the muscle fiber of rabbit external urethral sphincter is of the red and fast type.

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Recorded data show that males with obstructive diseases of the lower urinaly tract have low voided volume. Comparisons of flowrates between normal males and those with obstructive diseases are difficult because Maximum Flow Rate (MFR) and Average Flow Rate (AFR) increase proportionately with voided volume, especially when voided volume is below 200-300ml.
We developed a new parameter of Uroflowmetry which has been designated as MFR/Voided Time (MIT). Using MFR, AFR and M/T, we compared uroflowmetric studies between two groups: 30 normal males (160 studies); and 141 males with obstructive diseases (228 studies). In the latter group, 186 studies (82%) were with voided volume less than 200ml.
The results were as follows.
1) MFR and AFR in both groups increased proportionately with voided volume below 200ml.
2) MFR and AFR in normal males were almost constant with voided volume over 200ml.
3) MFR and AFR in males with obstructive diseases increased proportionately with voided volume over 200ml. The correlations between the two parameters (MFR or AFR) and voided volume were significant in patients with voided volume below 200ml. These correlations became significantly less in those with a voided volume over 200ml.
4) In a voided volume of 4 to 688ml, normal male M/T ranged from 0.58 to 3.90 (1.50±0.57), and in males with obstructive diseases the range was from 0.01 to 0.76 (0.23±0.16).
5) The correlation between M/T and voided volume in males with obstructive diseases was not significant, regardless whether the voided volume was below or above 200ml.
6) In analysing the number of overlap uroflowmetries in both groups, we found M/T to be statistically more selective than either MFR or AFR. Moreover, M/T was almost constant in males with obstructive diseases.
We found M/T to be the preferable parameter in the uroflowmetric study of low voiding males with obstructive diseases of the lower urinaly tract.

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Levels of human chorionic gonadotropin β-subunit (hCG-β) were determined in seminal plasma and serum of normal men, male infertile cases, klinefelter's syndrome, testicular tumor (seminoma), vasectomized cases as well as in normal prostatic fluids by radioimmunoassay.
The results were shown below.
1) The level of seminal hCG-β in normal men was 3.7±1.6ng/ml, several times as much as that in serum.
2) Concentration of serum hCG-β in healthy males was very low and we could not find any definite relations between serum and seminal plasma, but in 4 cases of testicular tumor (seminoma) it was at a high level in serum and at a low level in seminal plasma because of unilateral secretion. This fact suggests, besides tumor producing active hCG-β, invasive tumors destroyed the blood-testis barrier.
3) Levels of seminal hCG-β were found to be in significant correlations with sperm count, testicular volume and germinal cell index. This suggests that the secretory site of hCG-β was one process of spermatogenesis in human testis.
4) Levels of seminal hCG-β were found to be significantly correlated with seminal testotsterone and inversely correlated with LH, FSH in serum and seminal plasma. This finding also revealed that germinal cells had an intimate relation with the level of seminal hCG-β.
5) Levels of hCG-β in seminal plasma of azoospermia were 1.5ng/ml, similar to those with vasectomized seminal plasma and normal prostatic fluids that had no testicular hCG-β. Therefore, we suppose that about a half of hCG-β in seminal plasma was secreted by the prostate and the other half of seminal hCG-β was secreted by the testis.

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A sensitive double antibody radioimmunoassay (RIA) was developed for quantitation of the prostatic specific antigen (PA). By this method, PA can be detected at a concentration as low as 0.6ng/ml. Withinassay and between-assay errors revealed that this newly developed RIA was a reproducible technique.
Serum PA was determined by the PA-RIA in 33 normal males, 14 females and 201 patients with untreated prostatic carcinoma (22 cases), treated prostatic carcinoma (36 cases), benign prostatic hypertrophy (65cases), other malignancies (37 cases) and benign diseases (41 cases). Since a mean±2SD of 1.95±0.664ng/ml was obtained from a group of 33 normal males and 1.56±0.320ng/ml from a group of 14 females, the upper limit of normal range was set at 3.0ng/ml. Serum PA was elevated in 90.9% (20/22) of the untreated prostatic carcinoma, in 75% (27/36) of the treated prostatic carcinoma, in 67.7% (44/65) of benign prostatic hypertrophy, in 32.4% (12/37) of other malignancies and in 39.0% (16/41) of benign diseases. Positive detection rate in untreated prostatic carcinoma was 4/5 in stage A, 3/3 in stage B, 3/4 in stage C and 10/10 in stage D. The mean values of serum PA in 22 cases with untreated prostatic carcinoma and in 65 cases with benign prostatic hypertrophy were 129.1ng/ml and 5.25ng/ml, respectively. There was a highly significant difference (p<0.01) between them. Simultaneous assay of serum PA and prostatic acid phosphatase (PAP) was performed in 62 patients and there was a good correlation between them (r=0.96). In untreated prostatic carcinoma, 4 of 6 patients with normal PAP level showed abnormal PA levels.
The level of serum PA was affected by prostatic manipulations like massage, biopsy or surgery. But the elevated level of serum PA after the manipulation disappeared in 24 hours.
This study demonstrates that the clinical value of serum PA quantified by RIA is almost the same as that of serum PAP and the specificity of serum PA to prostatic carcinoma is not sufficient. Double tumor marker can be of an additive value in the diagnosis of prostatic carcinoma.

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Postobstructive changes of renal cortex were examined by electron microscopy in rat kidney. Following 1 week ureteral ligation, ureterocystostomy was performed in order to release the obstruction. On 3, 6, 12, 24 hours and 2, 4, 7, 14 days after ureteral release, rats were perfused and kidneys were removed. Electron microscopic examination revealed that massive loss of microvilli and cell swelling were noted in proximal tubular cells after release of obstruction.
These changes took nearly 2 weeks for recovery. Distal convoluted tubules showed cellular necrosis, which was not so severe as in proximal convoluted tubules. Gromeruli, on the contrary, showed no drastic change except for mild swelling of podocytes.

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