Jiro Ogata

Changes of Rat Urinary Bladder during Acute Phase of Spinal Cord Injury

Spinal cord injury (SCI) at Th13 was induced in female Wistar rats, and changes in the urinary bladder were examined during the acute phase of SCI. Wet weights of the spinal bladders increased twofold over controls by 7 days after SCI. Intravesical volumes increased sixfold over control values by day 3, and then decreased 7 days after the injury. Maximal pressure within the bladder decreased in all spinal rats compared with controls. Smooth muscle cells were isolated from the urinary bladder, and their total protein and DNA content were measured by multiparametric cytofluorometry. DNA content of isolated smooth muscle cells decreased by day 3 and remained 7 days after the spinal injury. Total protein content of isolated smooth muscle cells was decreased 1 day after and increased 7 days after the spinal injury, just when spinal reflex of the bladder recovered. These findings suggest that hypertrophy of smooth muscle cells in urinary bladder is related to the activity of peripheral autonomic nerve and that smooth muscle cells already begin to hypertrophy during the spinal shock period to adjust themselves to the new state, that is, the spinal bladder.

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.

Fungus ball formation of aspergillus in the bladder. an unusual case report.

An unusual case of fungus ball formation of Aspergillus in the bladder without any evidence of disseminated and renal aspergillosis is presented. A 49-year-old man whose chief complaint was progressively worsening dysuria after a stomach operation was admitted. Cystoscopy revealed many ball-like masses on the retrotrigone and left wall. Histological studies showed that these masses were composed of many Aspergilli. The uniqueness of the case and the route of infection are discussed.

Regulation of Prostaglandin Synthesis by Reduced Glutathione in Urinary Bladder Epithelium

A possible mechanism is presented by which reduced glutathione (GSH) regulates prostaglandin (PG) synthesis in microsomes of the porcine bladder epithelium. At a concentration of GSH less than 10(-5) M, microsomes produced more PGI2 and PGF2 alpha than PGE2. At a greater GSH concentration, PGE2 synthesis was remarkably enhanced. On the other hand, PGI2 and PGF2 alpha synthesis was inhibited. In the presence of 10(-3) M GSH, ten times more PGE2 was produced than the other PGs. The concentration of GSH in porcine bladder epithelium was about 0.6 mM. This reciprocal effect of GSH was also observed in rabbit and bovine bladder epithelium. These findings suggest that GSH is involved in the regulation of PG synthesis in urinary bladder epithelium. GSH may influence the physiological and pathophysiological changes elicited by PGs in the lower urinary tract.

Mechanism of Accumulation of the Antitumor Protein Antibiotic Neocarzinostatin in Bladder Tissue: Intravenous Administration, Urinary Excretion, and Absorption into Bladder Tissue

Some aspects of the absorption, distribution, and excretion of neocarzinostatin (NCS), a proteinous antitumor antibiotic, were studied in rabbits. NCS was given intravenously (i.v.) via the auricular vein, or [14C]NCS was instilled directly into the cavity of the bladder by tubing. In both groups, ureterostomy was performed, so that the drug excreted in the urine did not pass through the bladder. The results showed extremely rapid renal clearance; namely, two-thirds of the total recovered was excreted in the first 5 min. It was also shown that drug infused into the bladder cavity could be recovered in urine from the ureterostomized ureter. Also, the level of biological activity of NCS in bladder tissues after i.v. administration is significantly lower when ureterostomy is performed. Thus, evidence is presented for the absorption of NCS into bladder tissue from the lumen of the bladder. The high levels of NCS in bladder tissue are due to this effect as well as to accumulation via the iliac artery. These data should encourage further trials of NCS in bladder cancer. A study of urine containing NCS derived from i.v. administration showed an increase in antibacterial activity upon incubation, followed by a decrease. These effects are probably due to proteolysis, as shown by the appearance of a low-molecular-weight fragment and by the absence of such an increase in the presence of inhibitors of proteolysis.

Chemotherapy for bladder cancer with neocarzinostatin: Evaluation of systemic administration☆

Abstract Thirty patients with newly diagnosed bladder cancer were treated with i.v. neocarzinostatin. In 2 patients (6.7%) , the tumors disappeared completely. In 16 patients (53.3%) , a reduction to less than half of the initial size of the tumor was observed. In another 5 patients (16.7%) , the tumor was moderately reduced in size. In 6 patients (20%) , no effect was observed cystoscopically. Tumor growth was seen in 1 patient (3.3%) . Anorexia, general fatigue, slight weight loss and leukopenia appeared in most patients. Slight increase of S-GOT level was detected in 3 patients. However, these side effects were reversible and disappeared with the interruption of chemotherapy. All patients underwent transurethral resection after chemotherapy. Up to this date, although the periods of observation after treatment were 12–46 months, 5 recurrences (16.7%) have occurred. The recurrence rate was 3.3% (130) within 6 months , 6.7% (230) within 1 yr and 26.3% (519) within 2 yr . These results suggest that neocarzinostatin may be of value in treatment of bladder cancer.

An uptake of fluorescein isothiocyanate labeled neocarzinostatin into the cancer and normal cells

An uptake of fluorescein isothiocyanate labeled neocarzinostatin into normal and cancerous epithelial cells from bladder was investigated. Results showed that neocarzinostatin traversed the cell membrane into cytosol and nuclei, and it appeared to have a preferential cytotoxicity for the cancer cell.

Modulation of Platelet-Activating Factor Synthesis by Recombinant Interferon-α in Human Renal Cell Carcinoma

Platelet-activating factor (PAF), a potent phospholipid chemical mediator of inflammation, is involved in multiple cellular functions. Since PAF has a strong effect on platelet aggregation and on the enhancement of capillary permeability, it is possible that this factor plays an important role in tumor progression. In human renal cell carcinoma (RCC), it has recently been reported that immunotherapy with interferon (IFN) is effective for the prevention of tumor recurrence and progression. To evaluate the role of PAF and the effect of interferon-alpha (IFN-alpha) on PAF production in RCC, we measured PAF content and the activity of choline phosphotransferase (CPT), an enzyme involved in the de novo biosynthesis of PAF, in RCC specimens obtained from 30 patients who had undergone radical nephrectomy for RCC, and in specimens of normal renal cortex and normal renal medulla. PAF was present in both RCC and the normal renal tissues. Although CPT activity in RCC was similar to that in normal renal cortex, CPT activity in the normal medulla was significantly higher than that in RCC and the normal cortex. No correlation was found between CPT activity and the pathological findings in RCC. Although there was no difference in CPT activity in normal renal tissues between patients treated preoperatively with IFN-alpha and those untreated, CPT activity in RCC was significantly reduced in patients who had received IFN-alpha compared with those who had not. These findings suggest that IFN-alpha may modulate the production of PAF in RCC patients.

Pheochromocytoma of the Spermatic Cord: A Case Report

A case of pheochromocytoma arising from the left spermatic cord in a 52-year-old man is presented. The tumor had been present for about 10 years without hormonal symptoms. A diagnosis of pheochromocytoma was presumed because of a marked elevation of blood pressure at operation.

Role of Platelet‐Activating Factor in Two‐Kidney, One‐Clip Hypertension

Background: Platelet‐activating factor (PAF) is a bioactive phospholipid which is a potent hypotensive agent. To investigate the role of PAF in renovascular hypertension, we determined the PAF concentration and its production level assessed by the activity of cholinephosphotransferase (CPT) in renal tissue and examined the effect of a PAF antagonist on the mean arterial pressure (MAP) in control and two‐kidney with one clipped (2K1C) hypertensive rats.