The activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was measured in rat ventral prostate on the three conditions: castration, insulin administrated, and cholesterol rich diet feeding.
3 days after castration, the activity of prostatic HMG CoA reductase extremely fell down, but 5 days after, its activity was increased to the level equal to the control. Previously the influence of testosterone administration on the activity of prostatic HMG-CoA reductase was reported. The influence of testosterone to prostatic HMG-CoA reductase activity was completely transient.
In rat liver, the activity of HMG-CoA reductase was increased 2 hours after insulin injection. But in rat prostate, its activity was not increased after insulin administration. Therefore, probably insulin did not regulate the activity of prostatic HMG-CoA reductase.
It was well known that the cholesterol rich diet suppresses the hepatic HMG-CoA reductase activity. But prostatic HMG-CoA reductase activity was not suppressed by 1% cholesterol diet during 2 weeks. Exogenous cholesterol did not reveal a negative feed back for prostatic HMG-CoA reductase activity.

View full abstract

A survey of the diet was made in 61 patients with urolithiasis (10 females and 51 males) for successive two weeks. The results were compared with the results from the National Nutritive Survey and the Daily Nutritive Requirement in Japanese. There was no difference in the ingested amount of calories, total protein, fat, carbohydrate, phosphorus, and sodium. However, the ingested amount of calcium (Ca) was unexpectedly small, and the trend was remarkable especially in the patients who received the guidance for restriction on Ca. Futher more, it was found that ingested magnesium was of a very small amount because the ingestion of vegetables was insufficient. Nevertheless, the ingested amount of Ca and total protein was large in some patients.
Comparative study of excretions in the urine and the ingested nutriment on the same day was made. There was no relationship of any nutritive element to Ca excretions in the urine. The male patients were classified into the hypercalciuria group (250mg or more/day) and normocalciuria group. Comparison of the two groups in relation to the ingested nutriment revealed a significant increase of ingested total protein in the hypercalciuria group. Further more, it was suggested that the effect of ingested total protein on Ca excretions in the urine was great.
In view of these results, the following have been thought to be important as the first step to prevent recurrence of urolithiasis; a survey of the diet in each individual case and the guidance of the diet suitable for each individual case on the basis of the survey results.

View full abstract

Several vasoreactive agents were used in renal pharmacoangiography, so as to clarify the abnormal vascular pattern in the renal parenchyma. To estimate the suitable dose and the duration of vasoreactive agents in pharmacoangiography, the author studied the renal venous blood flow continuously by means of the local thermodilution method after the infusion of these agents into the renal artery. Adrenaline, dopamine and prostaglandin E₁ were examined.
Materials were composed of 32 kidneys in 26 patients who suffered from some urological renal disorders. The patients were 17 males and 9 females, the ages ranging from 14 to 79 years old (44.2 years old on the average). Split renal clearance was calculated from the extraction ratios of p-aminohippurate and sodium thiosulfate and the measured renal plasma flow.
Immediately after the infusion of adrenaline (5 or 10mcg), RBF began to decrease and reached a minimal flow rate (28 to 67% of control values) in 7 to 33 seconds. It was suggested that adrenaline was more effective in the patients with higher E_PAH or C_STS and that its duration was more prolonged in the cases of older patients. However, these were not significant statistically.
Dopamine (5 or 2mcg) caused an increase of RBF to a maximal flow rate of 123 to 169% of the control values in 11 to 51 seconds. The data suggested that its reactivity was correlated with E_PAH. This was significant statistically. The changes of RBF caused by both of adrenaline and dopamine returned to the control level within 100 seconds.
In cases of prostaglandin E₁ (10 or 20mcg), RBF increased to the maximal level (131 to 190% of control) within 47 seconds. The effects of prostaglandin E₁ were not correlated with age, renal vascular resistance, C_PAH, C_STS, E_PAH or E_STS.
In conclusion, a dose of 5mcg of adrenaline is sufficient for the renal pharmacoangiography in adult patients and the contrast medium should be infused after an interval of 10 to 30 seconds. The effect of 5mcg dopamine is steadier than that of prostaglandin E₁. The reasonable interval between the infusion of dopamine and contrast medium is about 10 to 30 seconds.

View full abstract

The efficacy of regional arterial infusion of an anticancer drug cis-diamminedichloroplatinum (II) (DDP)and systemic intravenous administration of its antidote, sodium thiosulfate (STS), was evaluated on rat bladder tumor in vivo.
Nine days after inoculation of NH-hepatoma cells (1.5×10⁶ cells) into the bladder wall, and at a time when the tumors were of finger-tip size, the chemotherapy was administered. In the group of “two route infusion” (Group A), a high dose of DDP (20mg/kg; LD₅₀×3) was infused into the abdominal aorta of the rat during interruption of arterial flow for 10 minutes and intravenous administration of STS in a dose of 1054mg/kg (100-fold molar ratio to DDP) was given twice; immediately after clamping and just before releasing the restriction. For comparison, other groups of DDP single treatment were made; Group B was given intraarterial infusion of 5mg/kg DDP (2/3 LD₅₀) with arterial flow interruption, Group C was given an intravenous administration of 5mg/kg DDP (2/3 LD₅₀) and Group D was treated by arterial flow interruption for 10 minutes. Sham operated controls (Group E) were also prepared. The efficacy of these compounds was evaluated by measuring bladder weight including the tumor at 14 days after the treatment.
The “two route infusion chemotherapy” (Group A) was found to exhibit the most excellent antitumor effect and no rat died. In this group, renal function assessed by measurement of blood urea nitrogen (BUN) was completely protected against DDP-induced toxicity. In contrast, 4 of 12 rats given intraarterial DDP alone (Group B) and 3 of 12 rats given intravenous DDP alone (Group C) died of DDP-induced toxicity. A marked elevation of BUN levels was observed in all rats of both B and C groups. The blood flow interruption alone (Group D) had no antitumor effect.
Thus an excellent antitumor effect and complete protection of STS against DDP-induced renal toxicity were obtained when the chemotherapy was given by two routes for the treatment of rat bladder tumor in vivo.

View full abstract

Electron microscopic studies were carried out on the 3 established cell lines; KK-47 and KW-103 were derived from transitional cell carcinomas of human urinary bladder and HCV-29 was originated from the benign-appearing transitional epithelium of a patient treated for a bladder tumor by irradiation.
Pellets of KK-47 cells grown in log growth phase at the 40, 120 and 200th passage levels were subjected to transmission electron microscopic studies. The cells at the 120th passage level were also studied by a scanning electron microscope immediately after subcultivation and 6, 12, 18, 24, 60 and 120 hours later. Concerning KW-103 and HCV-29, their colonies grown on Petri dishes 14 days after cell seeding were utilized for transmission electron microscopic studies.
The results obtained were as follows:
1. KK-47 and KW-103 cells closely resembled each other with respect to the transmission electron microscopic appearances. Round or oval nuclei with many protrusions, numerous microvilli, plentiful free ribosomes and desmosome-like junctional complexes between adjacent cells were observed in cells of both lines.
2. Well-developed rough endoplasmic reticulums and bundles of intracellular filament under the plasma membrane were observed in HCV-29 cells.
3. An increase of cell organella was observed in KK-47 cells at the 200th passage level compared to the earlier passage levels.
4. The scanning electron microscopic findings of KK-47 cells were characterized by a loss of contact inhibition as evidenced by piling-up, random arrangement and colony formation.
From these findings it was suggested that KK-47 and KW-103 cells had several morphological characteristics of transitional epithelial cells, the motility of HCV-29 cells was less than that of the other 2 cell lines as indicated by the presence of bundles of intracellular filament under the plasma membrane, and KK-47 cells were transformed during a long-term cultivation.

View full abstract

We have undertaken a comparative study of cystogram and histopathological findings of the patients with carcinoma of the urinary bladder (26 of them were treated with TUR (TUR group) and 20 were operated on for total cystectomy) after double contrast cystography by means of a universal gyroscopic X-ray TV apparatus. At the same time, preoperative transurethral echogram and histopathological findings were comparatively examined in 5 of the cases with total cystectomy.
We classified cystogram into six types according to the shape of mass: -0 (no abnormal shadow), A (papillary or narrow pedicle), B (broad pedicle), C (mountain-shaped), D (dish or bowl-shaped), and E (irregular relief). The alterations in the bladder wall at the base of the tumor masses were also investigated.
These studies showed that the masses of the total cystectomy group were larger in size than those of the TUR group and the shape of them was more frequently of C and D types. The larger alterrations in the wall were observed in the total cystectomy group. The higher the histopathological grading of malignancy, the greater the tendency for the shape of the masses to take C, D and E types.
In the group of total cystectomy, the higher the grade of invasion, the greater the tendency for the shape of the masses to take C and D types and alterations of the bladder wall were frequently visualized.
Transurethral echographic degree of invasion coincided with the histopathologic one in all cases but one, which revealed minimal invasion into lymphatics.
From the facts described above, we may conclude that more accurate preoperative diagnosis for carcinoma of the urinary bladder can be obtained by using double contrast cystography and transurethral echogram.

View full abstract

Arteriovenous fistulae secondary to renal cell carcinoma are uncommonly encountered, but these fistulae have much interesting clinical features.
Of 50 patients of renal cell carcinoma treated at the Jikei University Hospital during the 8 years from January 1972 to December 1979, arteriovenous fistula secondary to renal cell carcinoma was demonstrated angiographically in 6 patients.
In contrast to patients without renal arteriovenous fistula (average age 54 years old), patients with this pathological condition (average age 61 years old) were generally in the older age group.
Our patients did not show typical clinical picture when compared to patients reported from other countries. That is, the patient was female and presented with cardiovascular symptoms. But of these 6 patients, 5 were male and 1 was female. Severe cardiovascular complaints, which were reported previously in the literature on arteriovenous fistula associated with renal cell carcinoma, have not been reported in our country.
Among these 6 patients, the presence of tumor thrombus from the renal vein to the inferior vena cava was revealed in 3 cases (50%) by nephrectomy. On the other hand, the presence of tumor thrombus was revealed in 10 patients out of the remaining 44 patients (23%). Threfore, the patients with arteriovenous fistula associated with renal cell carcinoma have a high incidence of tumor thrombus, in contrast to those without it.
As to the clinical courses of the 6 patients, 2 of them demonstrated distant metastases (33%), and 12 patients of the remainning 44 (27%) demonstrated distant metastases. Thus, the patients with arteriovenous fistula did not show high incidence of complication of distant metastasis.
As to the prognosis, 2 of the 6 patients with metastatic lesion died and 1 of the 6 patients died of hemorrhage in the gastrointestinal tract after nephrectomy. On the contrary, 3 of the 6 patients who was nephrectomized have survived till now, from one year and 11 months to 2 years. Therefore, even in the presence of arteriovenous fistula associated with renal cell carcinoma, a prolonged survival period can be expected.

View full abstract

Seventy nine cases (51 males, 28 females) with renal cell carcinomas operated upon during the 17 years from 1962-1979 were histologically analyzed as to the postoperative survival rate. The overall relative survival rates 1, 3 and 5 years after the operation were 86.2%, 69.4% and 73.4%, respectively. On the grading based on nuclear atypia of tumor cells, 5 year relative survival rate was 87.5% in grade 1, 86.3% in grade 2 and 29.9% in grade 3. According to the tumor cell type, 5 year relative survival rate was 83.8% in cases of the clear cell type, 76.5% in the mixed type, 58.2% in the granular cell type and 0% in the spindle cell type. A significant difference in 5 year relative survival rate was also found between cases of carcinoma with the well circumscribed border (92%) and those with the poorly demarcated margin (35.3%). However, there was no significant prognostic difference in relation to the histologic types of carcinoma.

View full abstract

The levels of epinephrine and norepinephrine were determined in the tumor tissues and venous effuluent blood obtained from 12 patients with adrenal or ectopic pheochromocytoma. Several experiments were done to analyze the kinetic property of tyrosine hydroxylase of removed tumors.
Tissue concentrations of both epinephrine and norepinephrine in adrenal or ectopic pheochromocytomas were elevated. However, no significant differences were noted between the level of norepinephrine in venous effuluent blood from adrenal pheochromocytoma and that from ectopic pheochromocytoma.
Tyrosine hydroxylase activity in adrenal pheochromocytoma was found to be similar to that in ectopic pheochromocytoma. Preparation of tyrosine hydroxylase in adrenal- and ectopic-pheochromocytomas for quintessential conditions for protein phosphorylation resulted in the suppression of this enzyme Km for the cofactor. It appears reasonable to conclude from this study that phosphorylated condition can alter the tyrosine hydroxylase activity, subsequently influencing the biosynthesis of catecholamine in pheochromocytoma.

View full abstract

A quantitative microangiographic study on renal allograft in rabbits was carried out to determine the pathogenesis of acute rejection and hyperacute rejection as well as the mechanisms of action of immunosuppressive drugs.
Renal transplantations were performed on 42 rabbits, and they were randomly divided into two groups consisting of 26 allografts without treatment (group I) and 16 with immunosuppressive drugs (group II).
Immunosuppressive regimens were given in daily doses of azathioprine 1mg/kg orally, cyclophosphamide 1mg/kg and methylprednisolone 0.5mg/kg subcutaneously, immediately after renal transplantation.
Another 12 rabbits, presensitized with multiple skin grafts before the renal allografts and developed hyperacute rejection, were put into group III.
Each kidney graft, excised after 2, 4, 8, 16, or 24 hours, or on the 2, 4, 6, 8, 10, 12 or 14th day after renal transplantation, was examined histologically and microangiographically, and the following results were obtained:
1) In group I, interstitial mononuclear cell infiltration began to appear 16 to 24 hours after transplantation and became more conspicuous with time. Severe interstitial nephritis was found after a week.
Interlobular arteries and, especially, afferent arterioles, were temporarily narrowed in caliber (inner diameter) on the 2nd day, but showed gradual progress toward recovery from the 6th day, microangiographically.
Such temporary vasoconstriction of afferent arterioles and interlobular arteries preceded the glomerular lesions and was considerd to be a first step of the functional disturbances in acute rejection.
2) In group II, the interstitial mononuclear cell infiltration and the temporary vasoconstriction of afferent arterioles and interlobular arteries occurred as in group I. However, subsequent changes at the glomerular level were distinctly prevented (p<0.01), leading to prolongation of the graft survival period.
This suggests that immunosuppressive drugs may prevent one of the processes, in which immune lymphocytes cause lesions of the capillary walls.
3) In group III, striking vasoconstriction of afferent arterioles (approx. 44% of the normal thickness) and interlobular arteries (approx. 58% of the normal thickness) appeared temporarily within two hours after renal transplantation, and gradually recovered to approximately normal caliber after 24 hours. The glomeruli, however, began to decrease in number 8 hours after transplantation (p<0.01), and appeared to give rise to vasoocclusion and microthrombosis in glomerular capillaries.
These findings suggest that vasoconstriction at the levels of interlobular arteries and afferent arterioles may be the main cause of the development of hyperacute rejection.

View full abstract

Serum prolactin levels were measured in various urological patients by double antibody radioimmunoassay.
Serum prolactin levels of 113 normal men, whose age range was from 3 to 80 years with an average of 11.0±4.53ng/ml (Mean±S. D.), did not change with aging.
The mean serum prolactin level of patients with prostatic cancer was 9.1±3.34ng/ml and the prolactin level did not show any correlation to the clinical stages of prostatic cancer. The response to TRH in these cases was within normal range. From these data, it was considered that there was no hyperfunction in prolactin secretion from the pituitary gland in the patients with prostatic cancer.
In Klinefelter's syndrome, azoospermia and oligozoospermia patients, serum prolactin levels were also within normal range. In hypogonadotropic eunuchoidism patients whose plasma testosterone levels showed prepubertal values, however the prolactin levels were lower than those of normal adult males and the response to TRH was also diminished. Two factors might be considered to explain these results. 1) In hypogonadotropic eunuchoidism the diminished prolactin secretion may bear some relation to similar gonadotropin secretion. 2) The extremely low testosteronee levels may affect the secretion of prolactin from the pituitary gland.

View full abstract