Hiroaki Mizoguchi

Reduction of drug accumulation in cisplatin-resistant variants of human prostatic cancer PC-3 cell line.

We have isolated cis-diamminedichloroplatinum (II) (CDDP)-resistant variants, P/CDP4 and P/CDP5, from human prostatic cancer PC-3 cells after a stepwise exposure to CDDP. P/CDP4 and P/CDP5 showed 11-fold and 23-fold higher resistance to CDDP than did PC-3. P/CDP5 was cross-resistant to carboplatin, mitomycin C, etoposide, m-AMSA, bleomycin and UV irradiation. Alkaline elution of DNA showed an increased amount of DNA interstrand cross-links in PC-3 but not in P/CDP5 when PC-3 and P/CDP5 were cultured with CDDP. Flameless atomic absorption spectrophotometry revealed that intracellular accumulation of CDDP in P/CDP4 and P/CDP5 was decreased to 18 to 34% and 9 to 18% of that of PC-3, respectively, when PC-3 and its CDDP-resistant counterparts were incubated with 5 and 10 micrograms./ml. of CDDP for 24 hours. These data suggest that decreased drug accumulation is involved in the development of CDDP-resistance in the PC-3 cell line.

Three Approaches for Laparoscopic Unroofing of Simple and Complicated Renal Cysts

We report 2 cases of simple renal cysts which were marsupialized with 2 laparoscopic approaches involving either transperitoneal, with reflection of the colon medially or dissection through the mesocolon, and a case of a multilocular renal cyst which was treated by the retroperitoneal approach. Although laparoscopic unroofing of a renal cyst is a safe and effective alternative to open surgical techniques, the transperitoneal approach should only be used for simple renal cysts. The retroperitoneal approach for complicated renal cysts may be indicated if preoperative examinations exclude the possibility of malignancy.

A case of pseudodiphallia

A case of diphallia was presented. Roentogenographic and histological examination revealed pseudodiphallia without any other genitourinary anomalies.

A case of hemangiomyoma of the ureter in a child.

Herein a rare case of hemangiomyoma of the ureter in a child is reported. Benign mesodermal tumors of the ureter are not common, particularly in a child. Two cases of leiomyoma of the ureter in childhood have been reported to date. This is the first case of ureteral hemangiomyoma in a child. Nephroureterectomy was performed and the subsequent clinical course reveals no evidence of recurrence.

Giant Renal Artery Aneurysm in a Child

A case of giant aneurysm arising from the right main renal artery of a 6-year-old boy with severe renin-dependent hypertension is presented. As simple aneurysmectomy was hardly performed because of tight adhesion to the surrounding tissues, the aneurysm was removed with the kidney. The blood pressure was normalized 10 days after surgery. The size of the aneurysm was 8.0 cm in diameter. This is the biggest one among the child cases reported so far.

Pharmacokinetics and pharmacodynamics of bunazosin in patients with renal insufficiency.

The pharmacokinetics and pharmacodynamics of the alpha ( 1 ) -blocker bunazosin were studied in 9 patients with renal insufficiency and 11 healthy control subjects after a single oral administration of 3 mg. Plasma and urinary drug concentrations were determined using high-pressure liquid chromatography. The pharmacokinetic parameters of bunazosin elimination half-life and time to peak level were not statistically significantly affected by renal insufficiency. Peak level and area under the plasma concentration-time curve were significantly increased in patients with renal insufficiency compared with control subjects. In addition, plasma clearance and the apparent volume of distribution were significantly smaller in patients with renal insufficiency than in normal subjects. The urinary excretion of bunazosin was not affected by renal insufficiency. Although the normal subject group was not age matched with the patient group, it has been reported that the pharmacokinetics of bunazosin are not affected by age. These results suggest that hepatic metabolism is decreased in renal insufficiency. Concerning the pharmacodynamic effects, the changes in diastolic blood pressure and heart rate were weak but statistically significantly related to plasma bunazosin concentrations. There was no correlation between systolic blood pressure and plasma bunazosin levels. Hysteresis was observed between plasma drug levels and the pharmacodynamic effects.

In Vitro Parathyroid Hormone Release in Patients with Secondary Hyperparathyroidism

Background: The purpose of this study was to determine the precise endocrim. characteristics of parathyroid function in secondary hyperparathyroidism (sHPT).

Renal tissue and urinary kallikrein activity in two-kidney, one-clip hypertensive rats.

Renal tissue and urinary kallikrein activity were studied to assess the role of the renal kallikrein-kinin system in two-kidney, one-clip hypertensive rats. Body weight, urine volume, systolic blood pressure and urinary kallikrein activity were measured in 11 hypertensive rats and 6 normotensive rats 1, 4, 8 and 12 weeks after clipping or sham operation. The hypertensive rats used in the present study had systolic blood pressures of over 180 mm Hg 12 weeks after the operation and presented polyuria with a reduction in weight gain, which placed them in the malignant hypertension category. Urinary kallikrein activity in hypertensive rats significantly decreased from 21.7 +/- 13.3 nkat/day at 1 week to 11.6 +/- 5.5 nkat/day at 12 weeks after clipping (p less than 0.05), while urinary kallikrein activity in normotensive rats significantly increased from 23.6 +/- 8.9 nkat/day at 1 week to 43.7 +/- 16.2 nkat/day at 4 weeks after the sham operation. Significant differences were observed in urinary kallikrein activity between hypertensive rats and normotensive rats 4 and 12 weeks after the operation (p less than 0.05). Renal tissue kallikrein activity from bilaterally nephrectomized kidneys was investigated 12 weeks after the operation. No significant difference in tissue kallikrein activity was found between the two kidneys of the hypertensive rats. However, tissue kallikrein activity was significantly lower in the contralateral kidney of hypertensive rats as compared to the same kidney of normotensive rats (2.13 +/- 0.73 nkat/g in hypertensive rats vs. 3.05 +/- 0.69 nkat/g in normotensive rats, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the Kallikrein-Kinin System in Two-Kidneyed and One-Clipped Hypertensive Rats

The influence of aprotinin as a kallidinogenase inactivator on the antihypertensive effect of angiotensin I converting enzyme inhibitor (CEI) was studied in two-kidneyed and one-clipped hypertensive rats. Sixteen two-kidneyed and one-clipped hypertensive rats and sham-operated normotensive rats were prepared for this experiment. They were divided into two groups: those with the aprotinin infusion and those without. The effects of the oral administration of CEI were compared as regards mean arterial pressure (MAP) and urinary kallikrein activity (UKA). In 8 hypertensive rats under glucose infusion, MAP fell from 184.4 +/- 4.5 to 106.3 +/- 5.2 mm Hg, and UKA changed from 1.37 +/- 0.18 nkat/12 h to 0.61 +/- 0.11 nkat/12 h after the administration of CEI. In the remaining hypertensive rats under aprotinin infusion, MAP decreased from 175.0 +/- 3.0 to 140.6 +/- 5.1 mm Hg, and UKA slightly changed from 0.72 +/- 0.25 nkat/12 h to 0.59 +/- 0.12 nkat/12 h. Thus, the decrease of MAP after the administration of CEI was suppressed by the aprotinin infusion, and this significant difference was supported by the decrease of UKA. As for 16 normotensive rats, CEI did not alter MAP, nor did aprotinin have any effect on it. However, UKA tended to decrease after the administration of CEI. These results suggest that both the kallikrein-kinin system and the renin-angiotensin system play an important role in the maintenance of high blood pressure in two-kidneyed and one-clipped chronically hypertensive rats.

[Laparoscopy-assisted total nephroureterectomy for renal pelvic and/or lower ureteral cancer].

PURPOSE The usefulness of laparoscopy-assisted total nephroureterectomy for patients with renal pelvic and lower ureteral cancer is evaluated. MATERIAL Seven patients with renal pelvic cancer and four with lower ureteral cancer performed laparoscopy-assisted total nephroureterectomy from May 1997 to December 2000 (Ten males and one female, mean age 68.5 year-old). METHOD Of the 11 patients, the initial one received preoperative embolization of the renal artery. Under general anesthesia laparoscopy-assisted total nephroureterectomy underwent via transperitoneal approach in three patients and retroperitoneal approach in eight. After the kidney was completely dissected under laparoscopic procedure, it was delivered en bloc with ureter from the skin incision in the lower abdomen. RESULT Two patients needed conversion to open surgery. The mean operating time of nine patients except for conversion cases was 272 minutes and the mean blood loss was 313 ml. There was no major complication associated with laparoscopic procedure. There was no significant difference in both complication and recurrence rate between laparoscopy-assisted total nephroureterectomy and open surgery. CONCLUSION Laparoscopy-assisted total nephroureterectomy is an useful procedure for the treatment of patients with renal pelvic and lower ureteral cancer because it enables us to remove out the kidney and ureter from one small lower abdominal incision.