The pathogenesis of ascending Candida pyelonephritis has been histologically and bacteriologically studied in female rats which were transurethrally inoculated into the bladder with a Candida albicans strain, ATCC 10259. Serum concentration of D-arabinitol, a major metabolite of Candida species, was determined by gas-liquid chromatography to evaluate the usefulness in the diagnosis of Candida pyelonephritis. An experimental model of the ascending pyelonephritis was devised by the following procedures; cyclophosphamide was transperitoneally administrated at an amount of 200mg per kg of rat weight to suppress the host defence mechanism, and then, to induce a chemical cystitis, 0.5ml of a 0.75% acetic acid solution was transurethrally instilled into the bladder 2 days later, and on the next day a dose of 10⁷ cells of C. albicans was inoculated into the bladder transurethrally. Six groups of 15 rats were sacrificed 1, 3, 7, 14, 21 and 28 days after inoculation, respectively. Out of the total of 180 kidneys, 116 which were uncontaminated with any bacterium, were used for this study. The results obtained are as follows:
1. The incidence of Candida pyelonephritis was 29.7% (11 of 37 kidneys) within 3 days after inoculation and 78.5% (62 of 79 kidneys) for the period from 7 to 28 days after inoculation. In the 11 kidneys, acute inflammatory changes which partly extended into the medulla were observed, and 5 of the 11 kidneys were accompanied with papillary necrosis. The 62 kidneys revealed mild chronic inflammatory changes, localized mainly along with the pelvis, and Candida bezoars were found in 15 kidneys of the 62 kidneys.
2. There were significant relationships between renal Candida populations and grades of renal histological change except for the group of 3 days after inoculation.
3. There was a significant relationship between renal and urinary Candida populations (p<0.01). Candida pyelonephritis occurred in 26 of 30 rats (86.7%) which had more than 10 colony-forming units of C. albicans in their urine. The higher the urinary Candida population, the more severe the histological change
4. Serum D-arabinitol levels exceeded 0.2μg/ml of the detection limit only in rat groups within 3 days after inoculation. The mean serum concentration of D-arabinitol was 1.65μg/ml in rats with disseminated candidiasis, while it was 0.55μg/ml in rats with localized urinary tract candidiasis.
From these results, this experimental model was considered to be useful in the study of ascending pyelonephritis due to C. albicans. Furthermore, the determination of the number of Candida cells in urine and serum concentrations of D-arabinitol can be adopted for the diagnosis of Candida pyelonephritis and systemic candidiasis.

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The tissue energy metabolism of rat kidneys were evaluated using ³¹P nuclear magnetic resonance. Rat kidneys were not perfused and placed in lactate ringer with 10% D₂O after excision. The spectra showed well resolved resonance from the three phosphate groups of ATP, the two phosphate groups of ADP, AMP and inorganic phosphate. In the series of spectra as a function of time, ATP of renal tissue was relatively depleted. The metabolism of adenine nucleotide (energy metabolism) was slower at 4°C than 22°C. Consequently ³¹P NMR was a non-destructive method to follow continuously the metabolic state of the tissue.

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KK-47 cell line derived from a human bladder transitional cell carcinoma and KN-41 cell line from a human renal cell carcinoma were used for this experimental study. Asynchronous cells of these cell lines were subcutaneously transplanted in nude mice and the cells developed well-demarcated solid tumors at a high inoculation rate, and the tumors showed an exponential growth for a period from about 10 days to 21 days after inoculation. Two weeks after inoculation, the KK-47 and KN-41 tumors were utilized for the chemotherapeutic study. The therapeutic effects of anticancer drugs were evaluated in terms of the tumor growth curve, tumor regression rate and histopathological finding. Cyclophosphamide (CPA) was highly effective in the KK-47 tumors but not effective in the KN-41 tumors. Adriamycin (ADM) was found to be markedly effective in both the KK-47 and KN-41 tumors. Mitomycin C (MMC) exerted a high therapeutic effect on the KK-47 tumors and a mild therapeutic effect on the KN-41 tumors. Cis-diamminedichloroplatinum (CDDP) exhibited little therapeutic effect in the KK-47 tumors and a mild therapeutic effect in the KN-41 tumors. These data were in good accordance with in vitro chemosensitivities of these cultivated cells which were previously reported using a colony-forming assay system.
The combinations of 2 or all of CPA, ADM and CDDP were also studied together with body-weight loss following drug administration as a parameter of side effects. ADM plus CDDP, and ADM plus CPA plus CDDP were mildly effective on the KK-47 tumors. Concerning the KN-41 tumors, ADM plus CDDP was highly effective and ADM plus CPA, and ADM plus CPA plus CDDP were mildly effective.

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To trace the pathways of endocytotic vesicles from the luminal surface membranes of the principal cells of the caudal epididymis, horseradish peroxidase (HRP) (M. W. 40, 000) and dextran (M. W, 40.000) were infused into the epididymal lumen of normal and castrated rats. Attention was focused on the dynamic morphology of the Golgi apparatus and two kinds of vesicles of different sizes: large (100-150nm in diameter) and small (less than 50nm in diameter) ones. In principal cells of normal rat epididymis, both HRP and dextran were taken up into large vesicles and then into lysosomes 5-120min after infusion. In these cells of castrated rat epididymis, druing the period from 5 to 60min after infusion, HRP and dextran were first taken up into large vesicles and then into lysosomes and/or the Golgi cisternae and the tracers were absent in small vesicles originated from the Golgi cisternae. Some of the small vesicles containing the tracers, however, were certainly found in areas close to the Golgi cisternae, lysosomes and to the surface membranes 120-180min after infusion. These findings suggest that luminal surface membranes in castrated state are interalized by endocytosis and then fused with the Golgi cisternae in the form of large vesicles, and that small vesicles formed subsequently by pinching off from the Golgi cisternae are in part transported at least to the luminal surface membranes.

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The previous method which measures urinary acid excretion has various disadvantages in its measurement. The auto-recording titrable apparatus, by which the titration curve and its differential curve were calculated, were used to the measurement of the level of urinary weak acids.
Using this apparatus, we investigated the influences of 1) temperature 2) hematuria 3) urinary protein and 4) bacteriuria on the urinary pH and the urinary level of weak acids.
The results were as follows:
1. Urine specimens, when they had been left at room temperature for only 2 days, showed marked changes in the urinary pH and the level of weak acids. The specimens frozen at -20°C for 30 days, however, did not produce any changes.
2. The hematuria, which was clinically recognized as a marked macroscopic hematuria, does not influence on the level of weak acids in specimens. The slight increase of urinary pH was shown in the same experiments. This, however, does not seem to bring any unfavorable results to clinical practice.
3. Urinary pH and the level of titrable acid were not influenced by the addition of albumin and γ-globulin to the speciments, although the urinary level of NH₄⁺ was slightly increased in a few samples.
4. Bacteriuria with either E. coli, Pseudomonas aeruginosa or Proteus mirabilis, produced some increase of urinary pH and the level of NH₄⁺, and some decrease of the level of urinary titrable acid. The most prominent changes were observed in the cases of bacteriuria with Proteus mirabilis even after incubation of urine for 5 hours. In cases of bacteriuria, therefore, careful interpretation of results is necessary in the measurement of urinary pH, the level of urinary titrable acid and NH₄⁺.

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In obstructive uropathy, the urinary acidifying function, which is one of the renal medulla functions, is generally reduced in the early phase. Therefore, clinically, acidosis appears frequently in cases with slight decrease of GFR.
To investigate the degree of reduction of urinary acidifying function in obstructive uropathy, the weak acids are examined by titration curve analysis.
The results are as follows
1) The circadian rhythm with wide range of daily urinary acid excretion was observed in normal control group, but patients with acidosis due to renal insufficiency by obstructive uropathy did not show this rhythm.
2) After oral administration of ammonium chloride, normal control group showed approximately a double increase of total acid excretion, from 62mEq/day to 119mEq/day. In this increase of total acid excretion, TA is about 25% and NH₄⁺ is about 75%.
3) Some patients with obstructive uropathy had decreased concentration ability even when the GFR was normal. The function of acid excretion in tubules, however, was intact in such cases. This result indicates that the function of acid excretion depends on the GFR, rather than the concentration ability in kidney.
4) In these cases, however, plasma total CO₂ ([CO₂] p) becomes much lower than in the normal control, and this acidosis stimulates the renal excretion of urinary weak acids. Therefore, to estimate the urinary acidifying function, the clearance index of H⁺(net H⁺/1/[CO₂] p) is more effective than the net acid excretion.

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In unilateral hydronephrosis, GFR and urinary concentration ability are significantly decreased in hydronephrotic kidney than normal kidney. To investigate the degree of defect of urinary acidifying function in hydronephrotic kidney of unilateral hydronephrosis, urinary weak acids are examined by urinary titration curve analysis after the load of oral ammonium chloride.
The results are as follows:
1) The urinary TA, NH₄⁺, and net H⁺ were significantly decreased in hydronephrotic kidney compared to normal kidney in acid load test.
2) However, comparing the acid excretion per nephron which was obtained from the value of the acid excretion divided by GFR, no significant difference was observed between the hydronephrotic kidney and normal kidney. But in severe hydronephrosis such as those of grade D and E, the acid excretion per nephron was decreased than others.
3) In normal kidney, urinary acid excretion was much increased in compensation.

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A clinical study was performed on 50 patients who received kidney allografts from living related donors since Sept., 1973, through July, 1980, at Shakai Hoken Chukyo Hospital. The analysis was done in two separated groups. The group I (G-I) includes 20 transplants performed from Sept., 1973, through Dec., 1975, and group II (G-II) includes 30 transplants performed from Jan., 1976 throuth July, 1980. The reason why materials were devided into two groups was that a new postoperative regimen has been accepted since Jan., 1976. The essence of new postoperative regimen was low dose immunosuppressive therapy after transplantation.
The results were as follows.
1) Patient survival in G-II showed considerable improvement over that of G-I. One year survival rate was 70% in G-I, 97% in G-II and 3 year survival rate was 55% in G-I, 92% in G-II.
2) Comparison of the graft survival curves in G-I and G-II shows no considerable difference. One year survival of allografts were 65% in G-I, 70% in G-II and 3 year survival of allografts were 45%in G-I, 62% in G-II.
3) The deaths caused by infectious disease accounted for only 2 cases in G-II, compared with 5 cases in G-I.
4) Major infectious complications were occurred 41 times in 14 cases in G-I, and 15 times in 11 cases in G-II within 3 months after kidney transplantation.

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49 patients with idiopathic renal stone (24 hypercalciuric patients and 25 normocalciuric patients), 4 controls and 4 patients with primary hyperparathyroidism were studied with an oral calcium (lg of Ca) loading test and the comparison of urinary calcium excretion between in free diet and in low calcium (400mg/day) diet. Serum PTH levels and %TRCa⁺⁺ values, calculated by use of serum ionized calcium level were also measured.
The results were as follows:
1) From the results of the oral calcium loading test in 24 hypercalciuric patients absorptive hypercalciuria was suggested in only 3 cases, and renal hypercalciuria in 12 cases. Aiming to classify hypercalciuria in stone-formers by its own mechanisms, the results of the comprison of urinary calcium excretion between two different calcium intakes were roughly comparable to that of the oral calcium loading test.
2) In 20 cases (80%) of the 25 normocalciuric patients the urinary Ca/Cr values before and after the oral calcium load were normal. In all of the controls these values were normal, and were abnormal in all patients with primary hyperparathyoidism.
3) There was no significant difference in the serum PTH levels and the %TRCa⁺⁺ values between the patients with absorptive hypercalciuria and the patients with renal hypercalciuria by oral calcium loading test.
The oral calcium loading test appeared to have some usefulness, but did not classify all hypercalciuric patients into absorptive or renal types as clearly as expected. In addition, our results revealed a higher incidence of renal hypercalciuria than the previous reports.

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The localization patterns of fibronectin and laminin were studied in genito-urinary tumors and corresponding normal tissues by indirect immunofluorescent technique. In total, three testes, ten kidneys, ten bladders, four testicular tumors, six renal adenocarcinomas and fourteen bladder carcinomas were tested.
Fibronectin, a major component of non-collagenous glycoproteins in extracellular matrix, was detected on basement membrane and extracellular matrix of stromal tissues but not on epithelial cells both in malignant tumors and normal tissues. Therefore, the localization of fibronectin could be a useful histological marker for stromal reaction of epithelial tumor or differential diagnosis for epithelial malignancies from non-epithelial tumors, since fibroenctin was known to be positive in cytoplasm of non-epithelial tumor cells.
Laminin, a non-collagenous glycoprotein in basement membranes, was detected on only epithelial and vascular basement membranes in normal tissues. In genito-urinary tumors, however, the localization of laminin was different from tumor to tumor. Testicular yolk sac tumor seemed to be a laminin synthetic tumor because of a pattern of laminin localization which was found in extracellular matrix and cytoplasm of this tumor cells. In bladder transitional cell carcinoma, laminin was solely detected on basement membranes underneath lining epithelial tumor cells and endothelial cells of vessels, but not in cytoplasm and extracellular matrix. The basement membranes were definitely stained by histochemical staining for laminin, segregating tumor cells from stromal tissue in all tested bladder transitional cell carcinomas including four invasive bladder tumors obtained by cystectomy. As laminin was known as a protein localizing in lamina lucida of basement membranes, it was suggested that bladder tumors might invade deeply with coverage of a layer of lamina lucida, a component of basement membranes. Intermediate laminin synthesis was found in renal adencarcinomas, in which laminin was detected on pericellular matrix but not on cytoplasm of tumor cell. Taken together, different localization of laminin in genitourinary tumors possibly depends on laminin synthetic ability by tumor cells. Histochemical detection for laminin may be quite useful for the study on histological property of basement membrane or basement membrane material elaborated by tumor cells.

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In order to determine exact staging and to start rapidly additional treatment, clinical courses of 20 patients with AFP producing tumor were retrospectively studied considering theoretical and actual decay curve.
The results of the present study were summarized as follows: In 15 out of 20 cases (75%) it was shown that the results from both theoretical and actual decay curve coincide with the clinical course. In 5 cases the clinical course did not coincide with the results from the decay curves.
In 3 out of the 5 cases, the discrepancy has been clarified by careful examination. Thus, it was emphasized that careful evaluation of clinical course and theoretical and actual decay curve of serum AFP is of most importance in establishing the effective treatment of the testicular tumor. However, there is still a margin for further reseach of basic problems such as half life, metabolic clearance rate and interval of measurement of serum AFP.

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Since it was our impression that overall prognosis of low stage papillary tumors of the bladder is quite favorable, featrues of 94 patients with T₁ or less lesion who had been followed and alive for more than 5 years were analyzed to obtain an insight into its natural history.
63 patients (67%) had recurrence. The rate of recurrence was 53.2% at five years and 61.2% at ten years. The numbr of recurrences was one in 32% and more than six in 25%.
The first episode of recurrence took place within six months in 23.8%, within one year in 44.4%, but extremely delayed first recurrence such as later than 5 years after the initial therapy was noted in 20.6%. Patients of frequent recurrence had early recurrence, and the period of recurrence time was short.
In the first recurrence the tumor grade had not progressed from G₀, G₁ to G₂ or more, but this progression of tumor grade occured in 10% at the time of 2nd recurrence, in 21% at the third to fifth recurrence, and in 27% further later. The interval for this change to occur was 3 to 14 years after the initial treatment with a mean of 8.3 years. 3 with more than 6 recurrences died eventually of the progression of the infiltrative disease 6.5 to 14 years after the first admission.
In 8 patients the tumor stage had progressed from T₀, T₁ to T₂ or more in 3 to 14 years after the initial treatment with a mean of 7.7 years. At the time of first recurrence the tumor stage had not progressed but in 18.2% at the time of 2nd recurrence, in 18.7% at the third to fifth recurrence and in 18.7% further later and 3 patients eventually died.
The number of tumors was relevant to recurence rate, bacause multiple tumor has a higher recurrence rate than solitary tumor, 80% and 58.9% respectively. The recurrence rate was 71.2% with TUR and 53.8% with partial cystectomy.

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The protective effect of SOD (Superoxide Dismutase) to damage by warm ischemia was investigated in rabbit kidneys. At one week after right nephrectomy, the left renal artery, vein and ureter were temporarily clamped for 90min. At 30min. before clamp and just before the clamp was released, 0.5ml of SOD was injected i. v. to the animal. After the clamp was released, recovery time of renal colour was measured. Changes of serum level of creatinine and urea nitrogen were investigated periodically. On the 7th day after operation, the left kidney was removed and histological examination was performed
1) The kidney function of SOD treated group was better than that of on-treated group.
2) It is a useful method to use SOD intravenously for protection from damage by warm ischemia of the kidney in situ.

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To observe localization of adrenergic receptors in the proximal urethra, female mongrel dogs were operated to remove periurethral smooth and striated muscles sparing internal sphincter (internal sphincter dogs). Three weeks after operation, urethral pressure profiles were studied. Intact dogs were also used for the control of this study.
Results were as follows.
1) Increased urethral pressures in the proximal urethra were noted after phenylephrine administration to internal sphincter dogs as well as intact dogs.
2) Noradrenaline administration caused increased urethral pressure in intact dogs and decreased pressure in spite of the raised blood pressure in internal sphincter dogs. The affects of noradrenaline in internal sphincter dogs were blocked by pretreatment of propranolol. These decrease in urethral pressure by noradrenaline were similar to the effect of isoproterenol in the case of internal sphincter dogs.
Above results indicate that alpha as well as beta receptors are located in the smooth muscles of proximal urethra and that the latter seems to be predominant. Contractions of vessel wall by noradrenaline are thought to play little role in urethral pressure.

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Bladder tumor was induced in rats by oral administration of 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), after which Con A response of thymus lymphocytes as well as the effect of calf thymus humoral factor (THF) on Con A response were studied.
The results of this study are as follows.
1. Con A response of thymus lymphocytes began to decrease from the 8th week after BBN administration when the change in the mucous membrane such as hypertrophy in the bladder wall or vascular formation were noted, and a marked decrease in the response was noted from the 15th week when the tumor was visually recognizable. At the 20th week after BBN administration, massive hematuria was noted and the tumor was visually observed in about 95% of the rat bladders.
2. When THE extracted and prepared according to Goldstein et al. was applied in vitro to the thymus lymphocytes culture, an enhancement of Con A response of thymus lymphocytes was induced in the period between 8th and 20th weeks after BBN administration. However, after the 20th week, when the tumor in the bladder was observed in over 95% of the rats, the effect of THE was not clearly detectable.
3. In the period between 8th and 20th weeks after BBN administration, THE sensitive thymus lymphocytes, induced an enhancement of Con A response by the factor, were mainly separated in the low density fraction when rat thymus lymphocytes were separated into three fractions by discontinuous density gradient centrifugation combined with adhesion column method.

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Twelve patients with extensive renal calculi, treated by kidney autotransplantation and ex vivo surgery, are presented. Five of these patients had calculi in the solitary kidney and other 3 patients recurrent calculi in repeatedly operated kidney.
Calculi were removed completely in these 12 patients. However, 3 patients who had a solitary kidney, had infection with urinary leakage in the implanted kidney. One of the 3 patients recovered with good renal function, and the other 2 died from sepsis, developed from the infection. In the other 9 patients, operated kidneys recovered their function.
Kidney autotransplantation and ex vivo surgery are thought to be a suitable technique for removing extensive calculi completely from the solitary kidney or reoperated kidney. However, this technique has some complications such as massive bleeding from the operated kidney and transit renal dysfunction in early postoperative period, which might be caused by intolerance to cold ischemic and the operative damage to the renal parenchyma. Therefore, the approach for removing renal calculi should be done without injury to renal parenchyma during ex vivo renal surgery. This technique should be indicated to only the selective cases.

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Most renal cell carcinoma have a characteristic angiographic appearance, consisting of hypervascularity. Therefore, it has become one of the most useful tools in the diagnosis. But, about 5% of renal cell carcinoma lack neovascularity, and these tumors show a hypovascular or avascular angiographic pattern.
Between 1971 and 1980, 76 patients underwent nephrectomy for renal cell carcinoma, 5 of them were demonstrated a hypovascular or avascular angiographic pattern. The clinicopathologic features of these tumors were reviewed.
The age ranged from 58 to 76 years and the mean age was 64.2. 2 patients were male and 3 patients were female. Hematuria was the initial complaint in 3 patients. In 3 patients the tumor was located on the right side and in 2 on the left. By examination of the nephrectomy specimen, the tumors were restricted within the limits of the renal parenchyma (Robson's stage 1) in 4 patients, and only I patients had metastasis to the bone (stage 4B). The majority of hypovascular or avscular tumors (80%) were in the low pathologic stage.
Gross pathologic findings showed that in 3 cases of hypovascular or avsacular renal cell carcinoma, massive bleeding or necrosis was present. Microscopic pathologic findings showed that, 2 patients had an anaplastic histologic pattern, the other patients had a cystic histologic pattern or a solid histologic pattern, and in our series, only I patient had a papillary histologic pattern. It is important to emphasize that hypovascular or avascular renal cell carcinoma showed no alveolar pattern which is a usual histologic pattern of hypervascular renal cell carcinoma. There is no relationship among tumor vascularity, cell type, and histologic grading.
As to the prognosis of our 5 patients, 2 patients are without evidence of recurrence or metastasis from I year and II months to 6 years following nephrectomy. A patient with distant metastatic lesion died of pneumonia, 21 days following nephrectomy. Althourgh no evidence of tumor spread was noted at the operation, 2 patients died of D. I. C., and pneumonia from 7 months to I year and 2 months following nephrectomy. Considering histologic pattern and clinical course, a prolonged survival period can not be expected with these hypovascular or avascular renal cell carcinoma.

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Two cases of contracted bladder with positive autoimmune phenomena were reported. Case 1 was a 38 year old woman and case 2 was a 42 year old woman. Both cases had complained of gastrointestinal and urogenital symptoms such as nausea, vomiting, diarrhea, abdominal pain, dysuria and frequency. Serum antinuclear antibody of the two cases was positive. Contracted bladder and bilateral hydroureter-onephrosis had progressed for several months, and temporal urinary diversion was needed. Case 1 was recovered from contracted bladder spontaneously, but case 2 remained ill in spite of steroid therapy.

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A 23-year-old female was seen bacause of a mass in the left hypochordrium of 3 years duration. Excretory urography showed non-visualization of the left kidney. Arteriography, computed tomography and echography revealed a large tumor with cysts in the left kidney. Transthoracoabdominal left nephrectomy was carried out. The left kidney measured 21 by 13 by 11cm. and weighed 1381gm. The renal medulla, pelvis and upper ureter were entirely replaced by the tumor. The tumor consisted of a solid mass containing many cysts of various sizes. The renal parenchyma was thin, less than 5mm. in thickness.
Microscopically, the tumor was composed of both epithelial and mesenchymal components. The epithelial elements were made up of cystic and tubular structures, and the mesenchymal areas were angiomyomatous. However, fatty tissue was a minor element of non-epithelial portion of the tumor. This case was diagnosed as specific hamartoma histopathologically.
We think that this lesion was a transitional form from angiomyolipoma to congenital mesoblastic nephroma of adult.

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