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Biomedical subjects

S Ozono

Publications and source records attributed to S Ozono.

At least 145 records · Page 8Linked to original sources

[A clinical study of testicular tumors].

Thirty-one patients with testicular germ cell tumors were treated in our Department between January, 1979 and June, 1987. Of the 31 patients, 17 (54.8%) had seminoma and 14 (45.2%) had non-seminomatous germ cell tumor (NSGCT) histopathologically. Clinical stage of seminoma was stage I in 13 patients (76.5%) and stage II in 4 patients (23.5%). Clinical stage of NSGCT was stage I in 8 patients (57.2%), stage II in 1 patient (7.1%) and stage III in 5 patients (35.7%). The patients with stage II seminoma underwent high inguinal orchiectomy, radiation therapy, retroperitoneal lymphnode dissection (RPLND) and chemotherapy, and those with stage II and III NSGCT underwent high inguinal orchiectomy and chemotherapy. All patients with stage II seminoma are alive with no evidence of disease. Three patients with stage II and III NSGCT are alive with no evidence of disease, but 3 patients died of the disease. Survival of patients with stage I and II seminoma at 5 years was 100% Survival of stage I and II NSGCT and III NSGCT at 5 years was 100% and 40%, respectively. According to our experience, for patients with advanced seminoma, combination chemotherapy and RPLND as well as radiation therapy are effective. In addition, for patients with advanced NSCGT, adjuvant chemotherapy followed by RPLND is effective.

Adolescent↗

Effect of 1-hexylcarbamoyl-5-fluorouracil on development of rat urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The present study was conducted to examine the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. One hundred twenty male Fischer 344 rats were divided into 6 groups. Sixty rats (groups 1, 2 and 3) were given 0.05% BBN in drinking water for the initial 8 weeks of the experiment and another 60 rats (groups 4, 5 and 6) served as controls. HCFU mixed in the powder diet was administered at daily doses of 100 mg per kg of body weight. Group 2 received HCFU throughout and group 3 after BBN administration for 8 weeks. All animals were sacrificed at 20 weeks from the beginning of the experiment and examined histopathologically. In groups 1, 2 and 3, urinary bladder tumors developed in 13 of 18, 0 of 20, and 4 of 19, respectively. Incidences of tumors in the 2 groups treated with HCFU were significantly lower than that of group 1 treated with BBN alone. These results indicated that HCFU was effective in suppressing the incidence of bladder tumor.

Animals↗

[Experimental model of urinary bladder tumor in rats for evaluation of chemotherapeutic agents].

The chemotherapeutic agents were evaluated using the experimental urinary bladder tumor rat model induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Nine hundred and fourteen male rats received 0.05% BBN in drinking water for 8 weeks, and were divided into 35 groups to follow the regimens of chemotherapeutic agents. Thirty one groups received the agents after BBN treatment, and 4 groups were given the oral agents starting simultaneously with BBN treatment. All rats were killed at 20 weeks and incidence of the urinary bladder was examined histopathologically. The following 13 agents were evaluated; adriamycin (ADM), mitomycin-C (MMC), cyclophosphamide (CPM), 5-fluoro-uracil (5-Fu), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), neocarcinostatine (NCS), carbazil quinone (CQ), bleomycin (BLM), vincristine (VCR) and cis-diammine-dichloroplatinum (CDDP) were dosed intraperitoneally, and N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), 1: 4 mixture of FT-207 and uracil (UFT) and 1-Hexylcarbamoyl-5-fluorouracil (HCFU) were dosed orally. Among these agents, 5-Fu, FT-207, CQ, VCR, CDDP, UFT and HCFU were effective in inhibiting the incidence of urinary bladder tumor induced by BBN. In conclusion, the experimental bladder tumor rat model induced by BBN seems to be useful in evaluating the effective chemotherapeutic agents for a superficial bladder cancer. The importance of the experimental animal model for the evaluation of chemotherapeutic agents is discussed.

Animals↗

Modification of the Na+,K+-pump of glial cells within cobalt-induced epileptogenic cortex of rat.

The characteristics of a glial Na+,K+-pump dependent on extracellular K+ within epileptogenic cortex were studied electrophysiologically, biochemically and histochemically in vitro using slices from cobalt-induced epileptogenic cortex of rat. When the extracellular K+ concentration ([K+]o) was varied between 4 and 40 mM, the mean slope of membrane potential plotted against [K+]o was about 57 mV in glia from the normal cortex (tissue A) and about 44 mV in glia from the epileptogenic cortex (tissue B); whereas no significant difference in the resting membrane potential of these tissues was observed. In glia from tissue B, a marked transient hyperpolarization above control level was caused by replacement of elevated [K+]o with the normal medium. Ouabain abolished these phenomena observed in glia from tissue B, but had no effect on the membrane potential during normal [K+]o. Reduction of extracellular Na+, Ca2+ and Cl- did not significantly affect the membrane potential of glia from either tissue. In tissue A, the cells marked by intracellular injection of horseradish peroxidase after intracellular recording were protoplasmic astrocytes; in tissue B, fibrous astrocytes with abnormal processes predominated. K+-dependent stimulation of Na+,K+-ATPase activity of the astrocyte-enriched fraction and its membrane preparation from tissue B was much larger than that from tissue A. A certain amount of the reaction product of K+-pNPPase activity was seen on glial plasma membrane within tissue B but not on that from tissue A. The above findings suggest that a glial Na+,K+-pump within actively firing epileptogenic cortex may be modified to increase in its activity.

Animals↗

Involvement of pentylenetetrazole in synapsin I phosphorylation associated with calcium influx in synaptosomes from rat cerebral cortex.

To determine precisely how pentylenetetrazole (PTZ) is involved in the biochemical processes at the presynaptic nerve terminal, the effect of PTZ, under various conditions, on the phosphorylation of synapsin I (previously called protein I) was investigated, using 32Pi in synaptosomes from rat cerebral cortex. PTZ markedly stimulated the incorporation of 32P into this protein as determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and autoradiography, but it failed to stimulate protein phosphorylation in Ca2+-free medium containing ethylene glycol bis-(beta-aminoethylether)-N',N'-tetraacetic acid (EGTA). Moreover, the PTZ-stimulated synapsin I phosphorylation was reversed by addition of EGTA sufficient to chelate all external free Ca2+. PTZ also stimulated synaptosomal accumulation of Ca2+. The PTZ-stimulatory effects of both synapsin I phosphorylation and synaptosomal accumulation of Ca2+ were inhibited markedly by tetrodotoxin as well as by cobalt chloride and lanthanum chloride. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7, strongly) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5, weakly) reduced the PTZ-stimulatory effect on synapsin I phosphorylation by about 75 and 15%, respectively, whereas these antagonists had essentially no effect on PTZ-stimulated synaptosomal accumulation of Ca2+. These results suggest that PTZ causes the influx of Ca2+ into the presynaptic nerve terminal secondary to the elevated Na+ and is consequently involved in the synapsin I phosphorylation step, facilitating the Ca2+/calmodulin-mediated presynaptic event leading to seizure discharge.

Animals↗

Induction of high-grade, high-stage carcinomas in the rat urinary bladder.

The hypothesis that biologic aggressiveness of bladder cancer is determined by carcinogen dose was tested using heterotopically transplanted rat urinary bladders (HTBs). Young male Fischer rats, which were recipients of normal bladders, were divided into three groups; the first group received 0.5 mg of N-methyl-N-nitrosourea (MNU) into HTBs for six doses, a second, 0.05 mg for six doses and the third, 1 mg for three doses. Separately, a group of animals received bladders from rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in drinking water for 4 weeks; the transplanted bladders then were treated with 0.5 mg of MNU for six doses. Treatment with the larger dose of MNU resulted in a significant increase in tumor incidence and frequency of invasive carcinomas. The combination carcinogen treatment induced more invasive carcinomas than the single treatment. The data suggest that deeply invasive carcinomas may develop in two ways: the first is by emergence of a more anaplastic cell population within a pre-existing noninvasive carcinoma and the second is by the de novo development of an invasive carcinoma directly from a severely dysplastic urothelium, which is acceptable as carcinoma in situ. Squamous differentiation was characteristic of deeply invasive carcinomas. The dose of carcinogen(s) is a determinant of aggressiveness of bladder carcinomas.

Animals↗

Scanning electron microscopy of changes in the urinary bladder in dogs treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN).

The fine structures of the bladder mucosa during BBN carcinogenesis and of bladder tumors induced by BBN in dogs were examined by scanning electron microscopy. Normal dog bladder mucosa was covered with polygonal superficial cells with peaked microridges, but no microvilli. Microridges and uniform microvilli were observed in hyperplastic mucosa. In low grade papillary tumors induced by low doses of BBN, pleomorphic microvilli predominated. In dogs which received high doses of BBN, bizarre pleomorphic microvilli and blebs were observed in papillary lesions, whereas bumpy surfaces with thick short microvilli were observed in non-papillary lesions. These sequential changes which were observed in dog bladder mucosa during BBN carcinogenesis parallelled the changes that occurred in the process of chemical carcinogenesis in rodents, and dog bladder tumors were similar to those of rodents and of human bladder cancers.

Animals↗

Prophylactic treatment for superficial bladder cancer following transurethral resection.

A total of 130 primary cases with superficial bladder cancer were entered in the prospective randomized group study. The prophylactic treatments compared consisted in intravesical instillation of adriamycin (20 mg/-40 ml or 30 mg/30 ml), mitomycin C (20 mg/40 ml) or thio-TEPA (30 mg/30 ml), and noninstillation treatments with etretinate or tegafur; control patients were also studied. All agents were administered for 2 years. Recurrences were significantly suppressed in the instillation groups compared with control and non-instillation groups. Significant suppression of recurrence was observed in stage 1 or grade 2 disease treated with prophylactic instillation administered over the first 24 months of a 48-month observation period. These results may indicate the clinical usefulness of prophylactic instillation, but the long-term effect of intravesical instillation is still uncertain. A long-term follow-up study is therefore necessary.

Administration, Intravesical↗

Effects of single chemotherapeutic agents on development of urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats.

Chemotherapeutic agents were evaluated for effect on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in male Wistar strain rats. Seven hundred and two rats were given 0.05% BBN in drinking water for 8 weeks. After BBN treatment, the animals were divided into 26 groups to follow regimens of single chemotherapy. All drugs were administered intraperitoneally except in one group that was treated orally. In our experimental series, 5-fluorouracil (5-FU), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), carbazilquinone (CQ), vincristine (VCR) and cis-diamminedichloroplatinum (CDDP) were effective in inhibiting the incidence of bladder tumor, however, adriamycin (ADM), mitomycin C (MMC), neocarsinostatin (NCS), cyclophosphamide (CPM) and bleomycin (BLM) were not effective.

Administration, Oral↗

The application of microspectrocytofluorometric measurement of Feulgen nuclear DNA content to experimental tumors of rat submandibular gland. 1. Pathogensis and nuclear DNA content.

Pellets containing 9,10-dimethyl-1,2-benzanthracene (DMBA) were inserted into the submandibular glands of 65 male Fischer rats to determine the nuclear DNA content of both metaplastic epithelium during the process of development of squamous metaplasia (noted at 1, 2, 5, 7, 9, 10, 11, 13 and 15 weeks after insertion) and tumor cells of squamous cell carcinoma 24 weeks after insertion. From the second week of insertion onward, squamous metaplasia was found in excretory duct remaining epithelium in the tissues around the pellet. Dysplasia or a lining of metaplastic epithelium with atypia adjacent to pellets (i.e., formation of an epidermal cyst) was observed 5 weeks after insertion. Coincident with this dysplasia or metaplastic epithelium with atypia, variation in the nuclear DNA content was observed, showing the emergence of octaploids and a widespread histogram pattern with many peaks. Between 7 and 15 weeks, 25%-66% of the lining metaplastic epithelium showed variation in the nuclear DNA content due to shift of a peak (major mode) to a triploid as well as a vague major mode with the appearance of octaploids, etc. Tumors of the submandibular gland were recognized at 24 weeks in 11 (55%) of 20 rats. Nine were keratinized squamous cell carcinomas and the remaining 2 were carcinosarcomas. Marked abnormalities in the nuclear DNA content were observed in 5 of the 11 rats (45.5%), 3 with keratinizing squamous cell carcinoma and 2 with carcinosarcomas. In contrast, no marked variation in the nuclear DNA content was found in 5 rats in which the tumor was associated with cysts.

9,10-Dimethyl-1,2-benzanthracene↗

[Usefulness of computed tomography and ultrasonography for the early detection of renal cell carcinoma].

Eighty-three cases of renal cell carcinomas admitted to Nara Medical University and its related hospitals from August, 1962 through July, 1984 were reviewed. We have been using computed tomography (CT) and ultrasonography (US) for early detection of renal cell carcinomas since 1980. Thereafter the number of patients with low stage renal cell carcinoma was significantly increased. Furthermore 6 carcinomas were incidentally detected by CT and/or US examination for checkup of other diseases. We believe that CT and US may be valuable as a screening modality for early detection of renal cell carcinoma.

Adult↗

Stimulation of synapsin I phosphorylation in synaptosomes by convulsants.

Pentylenetetrazole markedly enhanced synapsin I (previously referred to as protein I) phosphorylation and synaptosomal uptake of Ca2+. Picrotoxin and strychnine sulfate caused a slight increase in the phosphorylation and no significant increase in Ca2+ uptake. The data indicate that pentylenetetrazole appears to influence this process.

Animals↗

Stimulation of rat bladder epithelial DNA synthesis by intravesical instillation of distilled water.

Two commonly used cystoscopic infusion fluids were examined to determine whether their infusion stimulates DNA synthesis of the bladder epithelium. Following a single intravesical dose of 0.5 ml of distilled water or 1.5% L-glycine solution, rats were killed periodically up to 1 week. A transient but significant increase in epithelial cell [3H]thymidine labeling was observed at 48 hr after distilled water instillation. Glycine solution did not stimulate DNA synthesis.

Animals↗

[Complete remission obtained in advanced testicular cancer treated by etoposide (NK-171)].

A 38-year-old man was admitted to Nara Medical University Hospital on Feb.7,1983, because of swelling of the scrotal contents on the right side and elevated serum AFP, beta-HCG and LDH suggestive of testicular tumor. Right orchiectomy was carried out and a pathological diagnosis of embryonal cell carcinoma of the right testis (pT3N0M1) was made. The patient, upon evidence of multiple pulmonary metastases, was treated with a combination chemotherapy of cis-Diamminedichloroplatinum, vincristine and peplomycin. After three courses of combination chemotherapy, pulmonary metastases were decreased, but their foci persisted. The patient was then treated with Etoposide 62 mg/m2 daily for 5 days every three weeks, and after this course, complete remission of pulmonary metastases was obtained. The patient recieved 3 courses of Etoposide and retroperitoneal lymph node dissection, and has since shown no evidence of disease for 2 years and 4 months after surgery.

Adult↗

Gamma glutamyl transpeptidase activity in rat urothelium treated with bladder carcinogens.

Gamma glutamyl transpeptidase (GGT) activity during urothelial carcinogenesis was examined histochemically in rats treated with N-methyl-N-nitrosourea (MNU) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). GGT-positive cells developed with a high frequency in foci of nodulopapillary hyperplasia and carcinoma. GGT-positive cells, both individually and in nests, were also frequent in foci of simple hyperplasia and interlesion normal urothelium of carcinogen-treated bladders. The results suggest that development of GGT-positive cells in interlesion normal urothelium is specific to carcinogen treatment.

Animals↗

alpha-Difluoromethylornithine inhibits cell growth stimulated by a tumor-promoting rat urinary fraction.

The growth stimulating activity of a tumor-promoting rat urinary fraction (Fraction I), and its inhibition by alpha-difluoromethylornithine (DFMO) were examined in vitro using a rat bladder carcinoma cell line, 804G cells. Cell growth was markedly stimulated by Fraction I when added to the basic medium containing 0.2% fetal calf serum (FCS). The increased proliferative activity was associated with an increase in ornithine decarboxylase (ODC) activity and intracellular polyamine content. DFMO effectively inhibited the growth of 804G cells stimulated by Fraction I or by 10% FCS, and the inhibition was associated with suppression of ODC activity and partial depletion of intracellular putrescine and spermidine. Growth inhibition was reversed by exogenous putrescine. These results show that (i) urinary Fraction I, both a tumor promoter in bladder carcinogenesis and an ODC inducer in 804G cells, has potent mitogenicity in 804G cells, and (ii) the mitogenicity is inhibited by DMFO, an irreversible inhibitor of ODC.

Animals↗