Hepatic dysfunction in renal allograft recipients has been recognized as one of the important complications with high incidence. There have been only a few reports about the relationship between hepatic dysfunction and graft function or chronic rejection. In order to delineate this relation, retrospective study of 66 adult renal allografts (including 4 cadaveric) functioning for 4 to 72 months was performed. A significantly lower incidence of chronic rejection was noticed in the group with hepatic dysfunction versus the group without hepatic dysfunction.
The results are summarized as follows.
1. We experienced two cases who had stopped receiving azathioprine and cyclophosphamide for more than two and a half years because of persistent elevation of s-GPT and/or s-GOT. No episodes of acute or chronic rejections were observed during these periods and they had good graft function. This fact and the report by Shriff indicate that the renal allograft recipients who had the complication of hepatic dysfunction or bone marrow suppression due to azathioprine and cyclophosphamide, could be controlled by discontinuing the administration of these drugs.
2. Forty of 66 recipients (61%) developed evidence of hepatic dysfunction. This was defined as elevation of s-GPT more than 50 IU for over 2 weeks.
3. Hepatic dysfunction occurred within 5 months after transplantation in all of the cases; twenty-eight of 66 (70%) of the cases occurred within 1 month.
4. There were 7 cases with hepatic dysfunction where azathioprine and cyclophosphamide were stopped because of persistent elevation of s-GPT (over 200 IU): 3 patients died from liver failure, 2 patients improved, and 2 cases (presented) had no significant changes of liver function.
5. Fourteen of 40 patients (35%) with hepatic dysfunction had acute rejection episodes versus 14 of 26 patients (54%) without hepatic dysfunction. This reveals no significant correlation between hepatic dysfunction and acute rejection.
6. In 26 recipients who were free from hepatic dysfunction there were 11 patients (42%) having chronic rejection, while in 40 recipients who had hepatic dysfunction there were only 7 cases (18%) with chronic rejection. A statistically significant correlation between hepatic dysfunction and chronic rejection was observed (p<0.05). No significant differences were observed in graft survival between the group with and without hepatic dysfunction. —There was no significant difference between the 2 groups in either histocompatibility as determined by mixed lymphocyte culture or follow-up period.
7. Thus, we conclude that Hepatic dysfunction may be beneficial to graft function, however the cause is obscure.

View full abstract

In order to investigate the actual site of urokinase production in the kidney, fibrinolytic activity in isolated glomeruli has been determined quantitatively or immunologically using a histochemical fibrinolysis autography and tissue culture.
The results obtained are as follows.
1. The glomerular fibrinolytic activity estimated by the fibrinolysis autography was significantly decreased after methanol fixation of the glomeruli. It was suggested that fresh isolated glomeruli had the ability of plasminogen activator production during incubation periods adopted for the fibrinolysis autography.
2. Using fibrin films incorporating antiurokinase serum in different concentrations, no inhibition of fibrinolytic activity in isolated glomeruli fixed by methanol was observed. In contrast, a significant inhibition of fibrinolytic activity was obtained in case of fresh isolated glomeruli. This showed that plasminogen activator activity released from isolated glomeruli into the fibrin films was identified immunologically as urokinase type.
3. The outgrowth of epithelial cells from in vitro cultivated glomerular tufts was observed in 6 to 8 days after explantation.
4. There was a considerable accumulation of plasminogen activator in supernatants of glomerular cultures from 6 kidneys, and their values ranged from 0.77 to 18.5 CTA units/ml.
5. Using fibrin plates incorporating antiurokinase serum in a final concentration of 1:1000, plasminogen activator activity seen in the supernatants was markedly inhibited. Percentage neutralization of the activator activity in the 6 cultures ranged from 88.7 to 100 percent. The majority of plasminogen activator released from in vitro cultivated glomerular tufts were referred to urokinase type.
6. Epithelial cells derived from in vitro cultivated glomerular tufts showed a marked plasminogen activator activity on the fibrinolysis autography.
These findings indicated that the fibrinolysis autography and tissue culture used were virtually useful for intimate studies of fibrinolysis in the kidney and the glomerulus would be a potent source of urokinase production.

View full abstract

Histochemical and biochemical studies have demonstrated a high content of zinc in the prostatic tissues. The previous histochemical works were carried out using dithizone method to show the zinc distribution in this tissue. Sulfide-silver method by Timm, on the other hand, seems to be applied to the investigation of the localization of heavy metal with light and electron microscopy. The aim of the present study is to observe the localization of zinc in the normal, hyperplastic and cancerous prostate, and ultrastructurally that in the hyperplastic prostatic cell using sulfide-silver method.
Specimens obtained during the surgery were fixed with 100% ethanol saturated with hydrogen sulfide. Sections were developed in the Timm's solution for 30 to 60 minutes, then examined stained or unstained with hematoxylin.
In the normal prostate, positive reactions were found in the prostatic epithelium of the peripheral acini, but not in the peni-urethral or inner glands. Hyperplastic prostate showed intensively positive reactions distributing in the apical part of cytoplasm. Silver granules were occasionally seen in the cytoplasm of cancerous tissue, while prostatic cancer after anti-androgenic treatment failed to demonstrate the reaction products of the silver-sulfide method. No positive reactions were seen in the nucleus of the normal and pathological prostate by light microscopic observation. Electron histochemical studies revealed the silver particles in the secretory vacuoles of the hyperplastic prostatic cell. In the control sections no deposit was demonstrated both in the cytoplasm and nucleus.
Therefore, in the hyperplastic prostatic cell, zinc localizes in the secretory vacuoles of the cytoplasm and is secreted into the lumen with merocrine or apocrine secretion. However, we have not performed the observation of the distribution of zinc in the normal or cancer cells of the prostate by electron microscopy. As more materials are processed, a deeper understanding of the role of zinc in the prostate will be expected.

View full abstract

RI angiography was performed on renal, bladder and prostatic tumors and intrascrotal lesions to assess the diagnostic efficiency and the limitation of this technique.
1) Using this technique for renal space occupying lesions, renal carcinoma and renal solitary cyst were found in 8 of 10 and all 5 patients respectively. Though the isotope angiograms were not comparable with ordinary angiographic films in the view point of resolution, this technique was regarded as a screening test.
2) The tumor image diagnostic method could detect bladder tumors in 35 of 50 patients. Accordingly, this technique does not seem to be so reliable in diagnosing the localization of tumors compared with other radiographic examination techniques. But this procedure was helpful not only for the diagnosis of tumors but also for the evaluation of the tumors in cases where it was difficult to use ordinary methods.
3) Distinct prostatic images were obtained in 1 treated and 6 untreated of 12 prostatic cancer patients using this technique. No prostatic images were obtained in the remaining 2 untreated and 3 treated patients.
Therefore, this technique would be applied for the evaluation of the treatment of prostatic cancer. On the other hand, benign prostatic hypertrophy reveald the accumlation of prostatic images in 2 of 10 patients.
4) A marked perfusion to the scrotal area was demonstrated in 1 testicular tumor, 1 orchids and 4 epididymytis.
In conclusion, in spite of the lower resolution power of this tool, RI angiography was found to be valuable in combination with a computer in processing images. RI angiography is safe, simple, rapid and useful as a screening test in urological diseases.

View full abstract

Macroscopic, microscopic observation and dissection were carried out on the urethral musculature running from the internal meatus to the posterior urethra of the male dog. Urethral pressure profile was also investigated with the same materials. Moreover, various drugs (adrenergic, cholinergic and muscle relaxant) were administrated, and those effects on the profile were investigated. The experimental results contained the following urethral pressure was divided by two main muscles, namely, the one was the smooth muscle, taking part in the extension of the detrusor muscle and drawing the flat profile in the prostatic urethra, and the other was the striated muscle which formed UPmax from the distal part of the prostate to the region attatched to the pelvic floor muscles. The tubular structure of the striated muscle played an important role of the sphincteric action.
According to the results of the urethral pressure profile with the sympathetic drugs administration, both the α-receptor and the β-receptor were confirmed to respond to the smooth muscle and the striated muscle of the urethra. Moreover, the α-receptor response was seen predominantly in the male canine urethra as reported by other investigators. The effect of the parasympathetic drugs administration on the urethral pressure profile was both stimulation and blockade in the prostatic urethra, but there was no response in the striated muscle of the urethra.
The striated muscle of the urethra, which differed from ordinary skeletal muscle in its character, assumed the special attitude of the striated muscle dominated by the sympathetic nerve.

View full abstract

A histological study on acquired urethral stricture was done. Besides hematoxylin-eosin staining (HE), periodic acid Schiff staining (PAS), alcian blue staining (AB) and toluidine blue staining (TB) were performed. In the normal glandular tissues of the urethra, PAS positive and also AB positive substances were observed. In the deformed or shrunk glandular tissues on the specimens from urethral stricture, only AB positive and TB metachromatic substances were observed, while PAS positive substances disappeared. The granulomatous tissues were stained strongly with AB and showed metachromasia with TB.
From the observed histological and histochemical changes on the urethral stricture, it is suggested that certain substances with strong acid radicals in the destroyed glandular tissues have some relation to the formation of granulomatous tissue which was observed at the site of urethral stricture.

View full abstract

Urological infections after renal transplantation are observed very often. It seems that they are not paid attention because most of urological infections are urinary tract infections which have usually high responsiveness to medical treatment. But in some cases, encephalomeningitis or lung infections are induced by them. Therefore, we have to prevent the infections.
We studied factors of urological infections in 26 infectious patients. Urological infections were detected in 26 (46.2%) out of 56 transplant recipients. Early infections within three months after transplantation were found 17 (34%) out of 50 patients. On the other hand, late infections after three months were 14 (32%) out of 44 patients. 15 out of 17 early infections affected the urinary tract (fourteen: urethrocystitis, one: pyelocystitis). The other 2 infections were perincephritis which were found at postmortem examination. Eight of fourteen late infections were epididymitis, which were classified into four urethrocystitis, two pyelocystitis and two prostatitis. The number of patients with urinary tract infections were only 11 (23%) out of 47 males, but there were five patients with urinary tract infections in nine female cases. There were urinary tract infections in 1.8 (55%) out of 33 patients with acute rejection and in 8 (35%) out of 23 patients without acute rejection. Early infections were observed in 14 out of 18 patients with both acute rejection and urological infection. Eight out of twelve patients with postoperative surgical complication of urological system (60%) fell into these infection.
Six patients in these cases suffered from early infection. However, eighteen patients in 44 patients (41%) without this complication also had the infections. Closed urinary drainage method with irrigation of bladder and urethra within 3 days after surgery were used in 22 patients. Then the infections were less frequent than in those treated by the opened method. The infections were observed in 5 (83%) patients with glycosuria more than three months after surgery. There were 20 (40%) with these infections out of 50 patients who were with or without slight glycosuria. 6 out of 14 patients with the spermatic cords cut off (43%) suffered from epididymitis. However, there were only two patients with epididymitis in 33 patients (6%), whose spermatic cords were intact.
As a result, it seems that the factors of early infections are acute rejection, early postoperative urinary drainage method and postoperative surgical complication of urological system. Cutting of the spermatic cord is one of the factors for late infections. On the other hand, sex and long-time glycosuria should be regarded as other factors for them. We should prevent them, although they are hardly paid attention. We have to make efforts to get early diagnosis and to treat as soon as possible, when we find them.

View full abstract

On 12 cases of renal adenocarcinoma, transcatheter embolization was performed and serum enzyme activities about LDH, ALP, CPK, γ-GTP, LAP and GOT were estimated following embolization.
Serum LDH activities were elevated in all cases and the peak levels (534-20550Wu/ml) were reached on the first or second day and all values returned to normal by the fifth or seventh day. Isoenzyme patterns of LDH 1-3 were increasing after embolization. Particularly LDH 1 increase exceeded LDH 2 in 8 cases.
Serum ALP activities were elevated in 4 cases and the peak levels (7.3-14.2BLu/ml) were reached on the fifth or seventh day. Isoenzyme patterns of ALP after embolization were increasing of ALP1.
Serum CPK activities were elevated in 8 cases and the peak levels (64-368mU/ml) were reached on the first or second day and all values returned to normal by the fifth day. Isoenzyme patterns could be determined in 6 cases following embolization and MM type (CK 3) and MB type (CK 2) were increased.
Serum γ-GTP and LAP activities were elevated in the same 5 cases. The peak levels of γ-GTP (74-280mu/ml) were reached on the fifth or seventh day and that of LAP (221-413 GRu) were reached on the sixth or seventh day.

View full abstract

A maldeveloped kidney frequently occurrs in association with a congenital obstruction of the upper urinary tract, which is considered to have muscular abnormality as the etiology. As part II of the study in a maldeveloped kidney, a development of the musculatures in the upper urinary tract was investigated histologically by serial sections in human fetuses.
The musculatures of the pelvis develop as early as those of the middle ureter in around the 16 week fetus. These musculatures extend to the each caliceal infundibulum around the 21 week and the caliceal musculatures develop in the latest stage as those of the intravesical ureter in the 23 week, but still showing immaturity even in the 27 week. Therefore, there is a discrepancy in comparison with the development of the caliceal musculatures and papillae, which already develop more prominent in the same stage, even in the 23 week. This may be the reason why a primary megacalicosis demonstrated with the abscence of the caliceal musculatures in the clinical case occurrs with the thin wall of the maldeveloped musculatures in the caliceal wall and shows non-obstructive dilatation, as a primary vesicoureteral reflux has been demonstrated to have an abnormal muscular development of the intravesical ureter.
The development of the ureteral musculatures including the pelvioureteral and ureterovesical junction was also investigated to obtain the following results. The musculatures primarily appear in the middle ureter having purely circular orientation in the 16 week fetus and develop to the craniocaudal direction. The musculatures of the both junctions remain in the circular orientation although other parts of the ureter except for the intravesical ureter with purely longitudinal orientation change oblique with growth. These observations correspond with the clinical results, namely the muscular abscence, disorientation or hypoplasia in the pelvioureteral obstruction or megaureter. As the megaureter is ascribed to a compression by the vas deference, so is the pelvioureteral obstructions to the vascular compression. By the histological observations of the obstructed ureters also, the forms of the maldeveloped musculatures may reflect the onset of the obstruction leading to the maldeveloped kidney.

View full abstract

It is well known that the urinary tract can also show immunoreaction as a part of the living body. The detection of urinary immunoglobulins is essential for the study of this process. Up to the present, as a detective method a single radial immunodiffusion (SRID) technipue has been usually used after concentrating urine 100-1, 000 fold. But by this method we frequently obtained inaccurate results because of the loss of protein during the course of concentration as well as because of its complexity.
To make up for this defect, we developed Enzyme-linked Immunosorbent Assay (E. L. I. S. A.) technipue using horseradish peroxidase as enzyme, which was easier and more correct. In this paper, we studied utility of this technipue in the detection of urinary immunoglobulins and we detected urinary IgG, IgM, IgA, SIgA and FSC separately in 34 healthy controls.
The detectable range of this method is 10μg to 10mg/dl, so the accuracy does not improve as radioimmunoassay (RI) but becomes much more sensitive them SRID and adequate to the urinary immunoglobulin level. The period needed for detection was 2 days, shorter than that needed for SRID after concentration of urine. Peroxidase reaction held in urine itself was negligible except in severe hematuria. Urinary IgG & IgM were detected with monospecific rabbit antisera in the same way as we did of the serum. Assay of IgA was performed after absorption of the samples with anti SC. FSC was detected after absorption with anti IgA. SIgA was detected with anti SC, based upon the result that the values of SIgA with anti SC as antibody were well correlated (r=0.97) to the values of SIgA using anti SC minus FSC.
The mean of urinary IgG was 352μg/dl; IgM 42g/dl; IgA 122μg/dl; SIgA 90μg/dl and FSC was 35μg/dl. The values were widespread, the standard deviation value being larger than the mean. These data concerning IgG and IgA are not so different from those of Bienenstock, Burdon and Turner. The values of IgG and IgM were strongly correlated, but not to that of SIgA. Thus we thought that these two groups of immunoglobulins were different in the mechanism of presence to the urinary tract.

View full abstract