In order to clarify the clinical aspects of sex chromosomal mosaicism, we evaluated the karyotypes, the anatomy of external genitalia and internal ductal system, the pituitary-gonadal function, and the histopathology of the gonads by immuno-staining for glutathion S-transferase (GST) in 5 patients who had been all raised as female.
Three patients have the 45, X/46, XY_q- karyotype in the initial lymphocyte culture or the subsequent culture of skin fibroblasts. Another two karyotypes were 45, X/46, XY_q-/47, XY_q-, Y_q- and 45, X/46, X_dicY. Thus, Y chromosome of all patients retained short arms in which the testis determining factor is encoded.
Three prepubertal patients were referred to us for their ambigious external genitalia and two postpubertal patients were for the short statures. Although the vaginal orfice was separated from the urethral meatus in all of them, the phallic enlargement was noted in 4 patients and the posterior labial fusion in 2 patients. The oldest patient had a normal female appearance of external genitalia except the vaginal septum.
Serum gonadotrophin (GnH) levels were basically high in the postopubertal patients and the responses of GnH to LH-RH were significantly increased in the prepubertal patients. Serum testosterone levels to hCG stimulation ranged from no response to low normal response.
All patients underwent the exploratory laparotomy together with the feminizing genitoplasty. The gonads in 3 patients, diagnosed as mixed gonadal dysgenesis (MGD), consisted of a unilateral testis and a contralateral streak gonad. Two patients had variants, including one with bilateral dysgenetic testis and another with bilateral streak gonads. Development of müllerian structures, a fallopian tube and uterus, was recognized in all of associated gonads. Epididymal tissue as wolffian structure was recognized in 2 of 5 testes and in 2 of 5 streak gonads. Histopathological examination of gonads, especially by the immunostaining for GST, revealed various extents of gonadal dysgenesis. The testicular tissue in prepubertal patients, composed of positive immunostained immature seminiferous tubules and the sparsely distributed interstitial Leydig cells, resembled that in the cryptorchid in prepubertal boys. Postpubertally Leyding cells, which were few in the absolute number, became hyperplastic and the deterioration of seminiferous tubules were in progress. The positive staining for GST in some cell lumps suggested the existence of ovarian granulosa cells in the streak gonad.
In MGD and its variants with sex chromosomal mosaicism, the dysgenetic variation of primordial germ cells is mainly resulted from the disarrangement of sex chromosomal constitution including testis determining factor and mosaicism, and this primary gonadal dysgenesis with its deficient müllerian inhibition and androgen production makes the ambigious external genitalia and the various degrees of wolffian development without the suppresion of müllerian development. Though the positive increase of serum testosterone to hCG stimulation implies the existence of testicular tissue, no change of serum testosterone to hCG stimulation does not contradict the testicular element. These dysgenetic gonads are further going to be deteriorated in accordance with high GnH stimulation.

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Donor specific blood transfusion (DST), given prior to living related kidney transplantation has resulted in significant improvement in graft survival. This improvement, however, has been accomplished with a high rate of adverse sensitization against the donor. In an attempt to reduce the incidence of sensitization, we have employed DST with intermittent coverage of cyclophosphamide. A comparative study was done between 2 methods of DST with or without the coverage of immunosuppressant for prospective kidney transplant recipients from living related donors. In addition, the beneficial effect of DST on graft survival was evaluated in our recent series of living related transplantation using cyclosporine A (CsA) as postoperative immunosuppression.
Twenty-nine prospective kidney transplant patients received 200ml of fresh whole blood 3 times at 2 week intervals from HLA one-haploidentical living related donors. The first 13 patients received DST alone, while the remaining 16 were given cyclophosphamide (CPM 1.5mg/kg/day) for 3 days prior to each DST. In patients with CPM coverage, 6.3% (1 of 16) developed positive T-warm antibody against donor and 15% of patients (2 of 13) with DST alone developed it. Like-wise 19% (3 of 16) of the former and 38% (5 of 13) of the latter became positive B-warm crossmatch. The difference in sensitization rates between these 2 groups was not statistically significant.
Nineteen patients receiving DST were compared to 21 non-DST patients in incidence of acute rejection, graft function and graft survival with the same immunosuppressive regimen, such as CsA, prednisolone, and mizoribine. One year and 2 year graft survivals were 95% and 89%, respectively, in DST group, and they were both 100% in non DST group. No statistical significance was found in graft survival, incidence of rejection episodes and graft function between the 2 groups.
In conclusion, the intermittent administration of CPM (1.5mg/kg/day) prior to DST seems to be non-effective to reduce sensitization against the donor, and no beneficial effect by DST was seen in CsA treated living related transplant recipients.

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Thirty eight patients with medullary sponge kidney (MSK) were detected (4.3%) in 881 patients with urolithiasis diagnosed by drip infusion pyelography in 12 years from January 1974 to December 1985.
Those with MSK were studied clinically and as to metabolism of urolithiasis. The results obtained were as follows:
1) Age distribution of the patients with MSK was the same as that of general stone formers.
2) Hematuria was observed in 20 patients (52.6%) and pyuria in 7, in whom 4 were positive by urine culture (E. coli in 3 and P. mirabilis in 1) and 2 of them had infective stones.
3) Renal function of the patients examined by PSP test (20 patients) and creatinine clearance test (21 patients) was normal in all of the patients but three with ureteral caliculi. Concentration tests performed by Fishberg method (12 patients) were disturbed in half of them.
4) Affected lesions wer detected at more than three pyramides in each kidney and the bilaterals were found in 32 patients (84.2%) and at less than two pyramides in each kidney and the unilateral or the bilaterals were shown in the other 6.
5) When urinary levels of calcium, phosphate, uric acid and citrate using 24 hours urine were compared with 37 patients with MSK and 100 general stone formers, there was no difference in hypercalciuria and hyperuricosuria accounting for the frequency of the patients with MSK and the general stone formers, but there was a tendency of increased frequency about hyperphosphaturia and hypocitraturia in the patients with MSK.
6) There was no significant difference in the components of stone between the patients with MSK and the general stone formers.
7) Urinary acidification test by acid loading with ammonium chloride was examined in 14 patients with MSK, resulting that no disturbance was found in 9 patients but acidification disorder was detected in the other 5. This was not observed in the patients suffering from acidosis which was detectable by blood gas analysis.
It was concluded that MSK was to be one of the etiological causes cotributing to hyperphosphaturia and hypocitraturia and disturbance of urinary acidification.

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A total of 75 cases of bladder tumors were treated with contact Nd:YAG laser therapy from February 1984 to April 1988. In 14 of 75 cases post-therapeutic total cystectomy was performed and laser irradiated areas were evaluated pathologically.
The results were as given below.
1. The irradiated are a was well demarcated from the non-irradiated area and had ulceration and granulation.
2. Ulceration extended to the deep muscle layer but no perforations were noted in any cases.
3. Although intensive edema was present in the fresh granulation, by approximately Post-irradiation week 3 the fibroblast cells and the fibrous cells had appeared and new vascular growth was manifest. A year later very small scarred tissues, distinctly demarcated from the surrounding tissues, appeared or the granulation was absorbed. Carbonized foreign bodies were incorporated in the granulation with the confirmed presence of the giant cells ingesting the foreign bodies.
4. With the exception of two cases where eosinophilic invasion was predominant, neutrophilic infiltration was predominant in the granulation throughout the cases.
5. In cases at Stage T3, the irradiated beds were suspected of having residual cancer cells.
6. Contact irradiation would not be accompanied by transfer of the cancer cells.
It was concluded that contact Nd:YAG laser therapy could be safely instituted in the treatment of bladder tumors in which transurethral treatment would be indicated.

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Utilizing two types of human renal cell carcinoma heterotransplanted in nude mice (JRC 1; papillary, avascular pattern, grade III, JRC 11; anaplastic and alveolar, hypervascular pattern, grade IV), we investigted the influence of tumor blood flow upon the effects of local hyperthermia (42.5°C), induced by 915MHz microwave. Blood flow was determined from the rate of thermal clearance by use of the bio-heat transfer equation. The rate of thermal clearnace was measured at intervals of approximately 10 minutes throughout the treatment session after turning off the microwave for 50 seconds.
With both strains it was necessary to increase the microwave power until the constant steady-state temperature of 42.5°C was reached. The JRC 11 strain needed more power for the constant temperature than JRC 1, but it needed a greater decrease in power level during the heating session to maintain a constant steady-state temperature. This was an indication that the tumour blood flow decreased more markedly in the JRC 11 strain.
In both tumours, a decrease of blood flow was observed during the heating session. In the case of the JRC 1 strain, it was observed that the mean value of blood flow was 1.87 times higher than that of JRC 11. This indicated a sharp reduction in blood flow in JRC 11 strain. This reduction was confirmed by the thermal clearance measurement at the end of the treatment session.
A sharp reduction in blood flow in hypervascular tumour (JRC 11 strain) is caused by a stasis of intra-tumoural blood circulation during the heating. This indicates that the clinical application of hyperthermia, especially in hypervascular renal cell carcinoma, is profitable, because there was a marked vascular reaction to the heating.

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Seminal findings and blood hormone levels were studied for evaluating the male reproductive function in patients with spinal cord injury. The patients were divided into 3 groups, namely, 18 patients with complete injury, 5 patients with incomplete injury and 3 patients with dyspermatism. The number of sperms, the rate of movement and rate of deformation were measured for semenm obtained by forced ejaculation. The number of sperms was kept at a relatively high level in the three groups, while the rate of movement fell off in all of the three groups. The rate of deformation was highest in the patients with complete injury and lowest in the patients with dyspermatism.
As for blood hormone levels, LH, FSH and Testosteron (herinafter referred to as TES) were determined by the RIA. The cases were classified into those in the acute stage and those in the chronic stage 3 months after sustaining injury for a comparative study. The subjects consisted of 27 cases in the acute stage and 47 cases in the chronic stage. For 8 patients in the acute stage, the blood hormone levels were determined even in the chronic stage and follow-up observations were made on the changes in the levels. The FSH level was low in both stages, while LH and TES tended to increase in the chronic stage. Particularly, the TES level was elevated in all the cases in the follow-up observations made in 8 patients.
From the results mentioned above, transient disturbance of the interstitial function is suggested as the mechanism of male gonadal disturbance due to spinal card injury.

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The effects of extracorporeal shock-wave (SW) exposure on the kidney were investigated in dogs using a Dornier kidney lithotriptor HM3. The SW was generated by spark dischrge at 20KV and was focussed on the lower part of either kidney. Before and after the exposure of 500 and 1000 shots of SW, the renal blood flow of the affected and contralateral kidney was measured by the microsphere method. The blood flow of the affected kidney decreased, but was comparable to that of the contralateral kidney immediately after the 1000 shots of SW. Renal scintigraphy using ^99mTc-DTPA was performed before the exposure of SW, and 30 minutes, 1 week, 2 weeks and 4 weeks after the exposure. The renograms were evaluated by the following parameters: T_max (time required to reach maximum radioactivity), RA_max ratio (maximum radioactivity of the affected kidney/that of the contralateral kidney) and T_1/2 (the half-life of elimination). T_max was significantly prolonged for the affected kidney 30 minutes after the exposure, while that for the contralateral kidney was shortened. The RA_max ratio was decreased 1 week after the exposure. T_1/2 was significantly prolonged 30 minutes after the exposure, which was observed till 2 weeks later. The scintigraphy also showed a slight enlargement of affected site. The histological study showed a hemorrhage in the peritubular space, indicating rupture of the peritubular capillaries. In conclusion, the main effect of SW exposure on the kidney was the rupture of the peritubular capillaries, resulting in temporary and reversible deterioration of renal function.

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In 113 patients with testicular germ cell tumor, the authors determined human chorionic gonadotropin (hCG) and the free β subunit levels in sera by differential quantitation using homologous hCG-β radioimmunoassay (RIA) and hCG enzyme immunoassay (EIA), respectively.
In 59 patients with seminoma, intact hCG was positive in 6 patients (10.1%), whereas free hCG-β was positive in 23 patients (39.0%). Syncytiotrophoblastic giant cells were detected in 4 cases out of 6 patients with positive intact hCG seminoma. Seventeen cases (28.8%) revealed positive free hCG-β only without elevation of intact hCG.
In 54 patients with nonseminoma, both intact hCG and free hCG-β were positive in 36 cases (66%). In some cases, hCG-β/hCG ratio increased up to 275% when recurrence of tumor developed.
Molecular heterogeneity of hCG is closely related to proliferation and differentiation of hCG producing cells. The differential quantitation of intact hCG and hCG-β using these two assays is valuable for clinical detection of molecular heterogeneity of hCG in testicular tumor.

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To investigate the role of microhematuria for the diagnosis of bladder tumor, the retrospective study of 156 patients with bladder tumor was done. Among the 156 cases, asymptomatic micro-hematuria was observed in 15 cases (9.6%) as an initial sign of the disease. Acording to the process to the final diagnosis, these 15 cases were classified into 4 groups; the Group 1 comprised 4 patients who consulted the urologist just after health examination; the Group 2 comprised 6 patients who consulted the urologist by the introduction of the general practitioner; the Group 3 comprised 2 patients who disregarded the sign and consulted the urologist after the appearance of symptoms; the Group 4 comprised 3 patients whose general practitioner overlooked the sign and who consulted the urologist after the appearance of the symptoms. The mean duration between the initial sign and the final diagnosis of each group was 2, 2, 8 and 62 months, respectively. Three of the 5 patients (60%) in groups 3 and 4 were treated by total cystectomy, while only 2 of the 10 patients (20%) in groups 1 and 2 totally cystectomized. High grade tumor was observed more frequently in groups 3 and 4 than in groups 1 and 2. Since the negative rate of urinary cytologic examinations of these 15 cases was 33.3%, cystoscopic examination was necessary for screening of bladder tumor.

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We encountered 4 patients with urolithiasis due to renal tubular acidosis (RTA) assosiated with Sjögren's syndrome.
Labolatory results about RTA in 4 patients with Sjögren's syndrome were not significantly different from those in patients who suffered from urolithiasis due to RTA without Sjögren's syndrome.
The incidence of urolitiasis in these cases was suspected to be higher than that in RTA patients without Sjögren's syndrome, because all 4 patients in this study had urolithiasis.
When we examine patients with bilateral and multiple urolithiasis, paticularly in middle-aged women, we should bear in mind that RTA and Sjögren's syndrome may exsist in the background.

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Intravesical insitllation of Tokyo 172 strain bacillus Calmette-Guerin (BCG) was performed on 137 patients with superficial bladder cancer (Ta and T1) after transurethral tumor resection as a prophylaxis against tumor recurrence. The recurrence rate of tumors was compared with that of historical controls and was estimated by the person-years method. There were statistically significant decreases in recurrent tumors following BCG therapy.
To clarify the efficacy of intravesical BCG therapy, prognostic significance of several factors were evaluated in 90 patients with initial bladder cancer treated with TUR and BCG instillation, and compared to those of controls. Prophylactic effects were statistically better for those with multiple tumors, grade 3 lesions or Ta lesions than for control patiens. No correlation between purified protein derivative responsiveness and favorable results could detected.
There were no marked side effects or fatal complications of BCG therapy during the observation periods.
Our results suggest that BCG is able to change the biological behavior of superficial bladder cancers with multiple, high grade or low stage lesions. The intravesical BCG instillation seems to be effective and safe as a prophylaxis against the recurrence of superficial bladder tumors.

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Seventeen patients with advanced uroepithelial cancer were treated with M-VAC regimen. Out of 17 patients, 10 were evaluable but 7 were not. Evaluable 10 patients comprised 7 males and 3 females ranging in age from 50 to 83 (median 69.5). The number of performed cycle ranged from 1 to 3 and the performans status was from 0 to 2.
Complete response (CR) was observed in 2, partial response (PR) in 4 and no change (NC) in 4 out of 10 patients. The efficacy rate was 60%. Every site of the tumor responded well and CR was observed, in particular, in nodal and pulmonary metastasis. One of 2 CR patients relapsed and died. One of 4 PR patients died of cancer, 2 are alive with regrowing tumors and the other is alive without disease after surgical removal of all residual tumors. The same regimen was carried out again to 2 patients with regrowing tumors, but no response was observed.
As to drug toxicity in total 31 cycles (17 patients), gastrointestinal disturbances, anorexia and alopecia were reversible but hematological toxicity was serious and 3 of 17 (17.6%) died of severe bone marrow suppression. M-VAC is an effective regimen for advanced uroepithelial cancer, but bone marrow suppression was serious. Therefore, special attention should be paid to myelosuppression.

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During the 13 years from 1976 to 1988, 160 patients with renal pelvic and ureteral cancer were reviewed based on a new general rule for clinical and pathological studies on renal pelvic and ureteral cancer of Japanese Urological Association. There were 71 renal pelvic cancers, 80 ureteral cancers, and 9 cancers in both regions. Patients ranged in age from 35 to 91 years old (average: 63). The involved side was right in 63 and left in 97. The most frequent symptom was hematuria, which was seen in 81.1%. IVP revealed the findings of filling defects, hydronephrosis, and non-visualized kidney in 99.7% of the patients. Total nephroureterectomy with bladder cuff resection was performed in 123 cases, nephroureterectomy in 16 cases, nephrectomy in 5 cases, partial ureterectmy in 10 case, and biopsy in 6 cases. As adjuvant therapies, irradiation was performed in 32 and chemotherapy in 123. Histologically, 156 were with transitinal cell carcinoma, one squamous cell carcinoma, one adeno-carcinoma and 2 unclear, the over-all survival rate of this study at 1, 3, 5 and 10 years were 86.8%, 73.0%, 65.3% and 45.6%, respectively. No patient with lymphnode meatstasis (N+) survived longer than 5 years. All patients with M(1) died within one year. There were no difference of prognosis between renal pelvic cancer and ureteral cancer. Regarding various prognostic factors, our series gave the same results as previous reports. However, it should be stresed that pathological grading was the most important prognostic factor.

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We reviewed data from 62 patients with epithelial tumors of the renal pelvis and ureter who were hospitalized and treated at Nagoya University Hospital between July, 1970 and June, 1988. Of the 62 patiens, 50 were males and 12 were females, the ratio being 4.2:1. The mean age was 62.1 years, the ages ranging from 41 to 87 years. The peak incidence of tumors was marked in the sixth decade for the males and in the seventh decade for the females. Eighty-two percent of the patients were 50 years of age or older. Smoking habits were noted in 76.0 percent of the males and in 16.7 percent of the famales. Asymptomatic macrohematuria, found in 43 patients, was the most frequent symptom. Ninety percent of the 62 tumors were transitional cell carcinoma. Twenty-five patients (40.3%) had concomitant bladder cancer, which was previously diagnosed in 3, simultaneously found in 9, and subsequently developed in 16. Twenty-nine patients had tumors localized in the renal pelvis and eighteen in the ureter; the remaining fifteen had tumors localized in two or three organs, including the renal pelvis, ureter and bladder. Histological grades of ureteral tumors were significantly higher than those of renal pelvic tumors. The sensitivity of urinary cytology was 57.8 percent. High-grade tumors had higher sensitivity than low-grade tumors. Larger tumors (>3cm in diameter) were significantly associated with high-stage tumors, whereas no apparent correlation was found between tumor size and histological grade. Nonpapillary growth of tumor and vascular invasion were significantly related with high-stage and high-grade tumors; diffuse pattern of tumor infiltration was associated with high-stage tumors.

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Urinary beta-2-microglobulin (β 2-MG), urinary N-acetyl-β-D-glucosaminidase (NAG), urinary creatinine (Cr) and serum creatinine level were measured in 79 patients with primary vesico-ureteral reflux. Comparing the data between conservatively treated group and operated group, between pre and post operation, we obtained the following conclusions:
1. From urinary β 2-MG and NAG, renal tubular damage tended to increase in both conservatively treated group and operated group in proportion to the grade of reflux. But the degree of tubular damage was more severe in the conservatively treated group than in the operated group.
2. Tubular reabsorption ability was lower in the operated group than in the conservatively treated group.
3. In patients with severe tubular damage, improvement of tubular function was seen at the early stage after operation.
4. Anti-reflux operation was shown to be effective even in improving glomerular function.

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A new form of hydroxypropylcellulose-adriamycin (HPC-ADM), which was supplemented with verapamil, a known calcium antagonist, in order to potentiate the antineoplastic effect of HPC-ADM, was synthesized and used for the treatment of superficial bladder carcinoma for clinical evaluation. The results are reported in this paper.
A total of 23 patients who were treated for bladder carcinoma during a 2-year period (1987-1988) were subjected in this study. All patients were diagnosed cases of superficial bladder carcinoma as follows; Ta, 3 cases, T1, 18 cases and Tis, 2 cases.
For the injection protocol, firstly HPC-ADM solution supplemented with verapamil was introduced into the urinary bladder via the urethra. After 2-3 weeks, the efficacy of the drug against the tumor was evaluated by cystoscope. Patients in whom the drug were found to be effective received increased adminstration of drug. In cases in whom the drug was found to be ineffective, different drugs for further treatment were adopted.
The average frequenty and amount of drug was 2.3 times and 45.2mg, respectively.
Complete responses achieved in 9 of 23 cases (39.1%). Of the 23 cases, 4 cases was with PR and 10 with NC. No cases were found to be with PD.
Side effects were observed in 4 of the 23 cases (17.4%), however, severe side effects were not recognized.
The important aspect in applying the method of intravesical therapy is that it makes enhanced antineoplastic potency possible with concomitant reduction of side effects and prevents the invasion of tumor.

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From 1977 to 1986, in the Chiba University Hospital, 107 cases of prostatic cancer with bone metastasis were experienced. In 10 of them spinal paralysis caused by spinal metastasis of prostatic cancer was observed.
Untreated five cases received endocrine therapy. One of them also underwent spine laminectomy and spinal instrumentation and regained the ability to walk. But the other cases treated by endocrine therapy showed only insufficient improvement of paralysis.
Five cases with spinal paralysis which were resistant to endocrine therapy were treated by chemotherapy or radiation to the site of bone metastasis. One of them underwent laminectomy and spinal instrumentation. However, most cases showed no improvement of paralysis.
It is concluded that spinal surgery is recommended in untreated cases for the sake of quality of life, but in cases with hormone resistance spinal surgery should cautiously be applied.

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Four male patients with invasive bladder cancer, 44 to 68 years old in age, underwent bladder replacement with ileum after radical cystectomy.
In three patients an ileal segment alone was isolated for construction of neobladder, and in the fourth patient, the terminal portion of the ileum, the cecum and the proximal part of the ascending colon were isolated for the bladder replacement. In all the cases isolated segments were detubularized for obtaining a low pressure reservoir.
All the patients, except one who had a past history of cerebro-vascular disease and was performing intermittent self-catheterization because of a kind of detrusor-sphincter dyssynergia of the ilealneobladder, are now enjoying almost the same voluntary urination as before the operation.
Serum creatinine, BUN and electrolytes are all normal during the postoperative observation period, although a very slight metabolic acidosis was observed in 3 patients.
Ten to 16 months have passed without any complications and all the patients are alive without any sign of tumor recurrence or metastatic involvement.

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Case-1 (24-year-old female) had complained of slowly progressive urinary incontinence (since 14 years old) and gait disturbance (since 18 years old). A marked pyramidal disorder was observed, and anti-HTLV-1 antibody (1:640) was present in her peripheral blood. She was diagnosed as having HLTV-1 associated myelopathy (HAM). Repeatd urodynamic studies (UDS) revealed exacerbation of overactive bladder and detrusor-sphincter dyssynergia (DSD) with the progress of the disease.
Case-2 (48-year-old male) had complained of gait disturbance (since 32 years old) and progressive urinary hesitency (since 46 years old). Physical examination revealed a marked pyramidal disorder. Anti-HTLV-1 antibody (1:200) and ATL-like cells were present in his peripheral blood. He was diagnosed as having HAM. The voiding cystourethrography demonstrated an abnormal change of the bladder wall. UDS revealed overactive bladder and marked DSD.
Medications based on adrenocortical steroids and urlogical cares have improved urinary disturbance, in both cases.

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