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Biomedical subjects

Y Tagawa

Publications and source records attributed to Y Tagawa.

At least 199 records · Page 11Linked to original sources

Cell proliferation induced by uracil-calculi and subsequent development of reversible papillomatosis in the rat urinary bladder.

The sequence of cellular alterations in urinary bladder epithelium associated with uracil-induced reversible urolithiasis was investigated in male F344 rats. Initial changes were submucosal edema with occasional mucosal erosion or ulceration which appeared on Day 2 of uracil administration. Simple hyperplasia of bladder epithelium was already evident at this time and calculus formation was noted as early as Day 4. Labeling indices in the bladder epithelium assessed by bromodeoxyuridine incorporation were about 32% on Day 4 and then gradually decreased to 6% at Week 8 and 4% at Week 25 of chronic treatment. Histologically, a direct progression from simple hyperplasias, through papillary hyperplasias to papillomatosis, accomplished by Week 5, was evident. Dysplastic lesions were also apparent by Week 25. Topographically, papillomatosis was composed of marked interconnecting mucosal ridges of relatively uniform width. No polyp-like protrusions were present and the vascular pattern revealed by resin perfusion casting demonstrated that these mucosal lesions were supported by a uniform plexus of capillary vessels. After withdrawal of uracil from the diet the labeling index dropped dramatically to 0.002% after 1 week and urolithiasis and papillomatosis had disappeared by Weeks 2 and 3, respectively. The findings suggest that papillomatosis associated with uracil-calculi is a hyperplastic rather than a neoplastic response and that induction of putative neoplastic lesions is directly related to prolonged vigorous cell proliferation.

Animals↗

[A significance of dual parameter flow cytometric DNA analysis using the anti-keratin antibody].

Flow cytometric DNA analysis using the anti-cytokeratin antibody was carried out in order to estimate more reliable measurement in single cell suspension obtained from solid tumors. It was difficult to detect a DNA aneuploidy with DI of 2.0 by one parameter analysis of DNA. Whereas it could be detected easily by using dual parameter analysis of cytokeratin and DNA. And also, the pattern of DNA multiploidy could be selected for cytokeratin positive cell population by gate analysis.

Antibodies↗

[Study of fluorescence in situ hybridization for detection of chromosome aberration].

The authors applied fluorescence in situ hybridization (FISH) technique for the detection of chromosome aberration in interphase nuclei using the probe specific to alphoid repeats on chromosome 11 and X. Chromosome 11 specific probe showed two major spots in lymphocyte nuclei, while X specific probe showed single spot in male and double spots in female respectively. On the other hand three spots were detected in most of the nuclei from HeLa cells with 11 and X specific probes. We concluded that FISH with the use of chromosome specific probe may become a useful and reliable tool for the detection of chromosome aberration in interphase nuclei.

Cell Nucleus↗

[A case of pulmonary carcinoma presenting flow cytometrical heterogeneity of the nuclear DNA content between its primary focus and the metastatic foci].

We have experienced case involving a 63-year-old patient with a pulmonary carcinoma, who was given an enterectomy following a lobectomy, due to minimal intestinal metastasis. In this case, using flow cytometry, the cancer cell nuclear DNA content was analyzed for the primary tumor focus, the mediastinal lymph node metastatic focus, and the small intestinal metastatic focus. For the primary focus, a cancer cellular population of polyploidy with 2 ploidies of DNA content was observed, while for both the metastatic foci, only a single cancer cellular population was observed, indicating the heterogeneity of the nuclear DNA content between the primary focus and metastatic foci. These 2 metastatic foci had DNA contents completely corresponding to that for a ploidy with a high DNA content in the primary focus, suggesting a metastasis of only the above population from the primary focus. The present case apparently formed metastatic foci in other organs than the lungs but only by cancer cells more susceptible to metastasis among the cancer cells found in the primary focus.

Aneuploidy↗

[Pharmacokinetics of cisplatin and vindesine in a patient with chronic renal failure undergoing hemodialysis].

Plasma total platinum and vindesine levels were monitored in a patient with chronic renal failure undergoing hemodialysis. Plasma levels of cisplatin were determined as platinum by atomic absorption spectrophotometry, and plasma vindesine levels were measured by radioimmunoassay. Fifty mg. of cisplatin in combination with 3 mg. of vindesine were infused for 60 minutes before dialysis. During dialysis, plasma total platinum levels decreased rapidly in a biphasic fashion and 1.76 at 30 hours after infusion. Plasma vindesine levels declined with higher concentration. In conclusion, it is considered that cisplatin and vindesine can be given to anuric patients undergoing hemodialysis. However, it is suggested that smaller doses should be given to prevent side effects.

Antineoplastic Combined Chemotherapy Protocols↗

[Changes of protein and RNA content in accumulated G1 cells by delta12-PGJ2].

Protein and RNA content in accumulated G1 cells was measured with B16 melanoma cells by flow cytometer to study the mechanism of antineoplastic action of delta 12PGJ2. DNA histogram showed that, after a 6 hr exposure to delta 12PGJ2, the percentage of tumor cells in G2M phase increased, and G1 accumulation with depletion of cell population in S phase was seen after 12-24 hr exposure to 2.0 micrograms/ml of delta 12 PGJ2. Protein content in accumulated G1 cells increased at 6 hr after exposure, and subsequently decreased. However, the protein content treated with delta 12PGJ2 was higher than that of the control. A reduction of RNA content in G1 cells was seen after delta 12PGJ2 exposure. As the result, it was found that delta 12PGJ2 made cell progression ceased in G1 phase of cell cycle, and where protein and RNA content was higher than that of control. It is suggested that some hyper-metabolite state was caused by delta 12 PGJ2 in cultured B16 melanoma cells.

Antineoplastic Agents↗

Variation in tumor yield in the prostate and other target organs of the rat in response to varied dosage and duration of administration of 3,2'-dimethyl-4-aminobiphenyl.

The effects of varying dosages of 3,2'-dimethyl-4-aminobiphenyl (DMAB) in combination with cyclic dietary administration of ethinyl estradiol (EE) on induction of prostate carcinoma were investigated in male F344 rats. Animals received repeated treatment with 0.75 ppm of EE for 3 wk with intervals of 2 wk on basal diet. The cycle was repeated 10, 5, and 3 times in Groups 1, 2, and 3, respectively, a single s.c. injection of DMAB being given 2 days after each change to basal diet at a dose of 50 mg/kg of body weight in Group 1, 100 mg/kg of body weight in Group 2, and 167 mg/kg of body weight in Group 3. With this dosing schedule, the total dose of DMAB (500 mg/kg of body weight) per rat was the same in each group. Subsequent to the last treatment with EE, all rats were given basal diet until the end of the experiment (Wk 60) when all surviving animals were sacrificed for histological examination. Carcinoma of the prostate was found in 58.6, 45.0, and 25.9% of rats surviving for 60 wk in Groups 1 to 3, respectively, the incidences of atypical hyperplasia being 86.2, 85.0, and 74.1%. However, tumors of the small and large intestines, preputial gland, and pancreas developed in a dosage-dependent manner, the largest incidences being found in the group given 167 mg of carcinogen 3 times. Thus the present experiment confirmed that administration of DMAB combined with cyclic treatment with EE induces a high incidence of prostate carcinoma in rats and demonstrated that a low dosage of DMAB given over a long period is superior to a high dosage over a short period for specific induction of prostate lesions.

Aminobiphenyl Compounds↗

Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats--an approach for a new medium-term bioassay system.

A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and starting 2 weeks later were treated with test compounds for 6 weeks and then killed, all rats being subjected to two-thirds partial hepatectomy (PH) at week 3. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive (GST-P+) foci in the liver with those of the corresponding control group given DEN alone. Positive was scored for a significant increase in the value of GST-P+ foci, negative for no change or a decrease. Results were compared to reported Salmonella/microsome and long-term carcinogenicity test findings. Of the liver carcinogens, 10 out of 11 (90.9%) mutagenic, and 11 out of 13 (84.6%) non-mutagenic compounds gave positive results (mean, 87.5%). Carcinogens other than the hepatocarcinogens gave less positive results (two out of 17, 11.8%). None of the compounds reported as non-carcinogenic demonstrated positivity suggesting that the assay system does not suffer from the disadvantage of false-positive results. The protocol system also provided information concerning the inhibitory potential of compounds such as anti-oxidants. It is concluded that the present experimental protocol which requires far fewer animals and shorter duration than a long-term carcinogenicity test has practical applications for the rapid and economical screening of environmental hepatocarcinogens and their inhibitory agents.

Animals↗

Low tumorigenic response to 3,2'-dimethyl-4-aminobiphenyl administration in the prostate of rats castrated at birth.

Six-week-old rats which had been orchiectomized at birth were given 3,2'-dimethyl-4-aminobiphenyl (DMAB) at various doses combined with a stimulus to prostate epithelial cell proliferation in the form of oral administration of methyltestosterone (MT) for 4 weeks. Thereafter MT treatment was continued or the animals received subcutaneous implants of testosterone propionate (TP) and were maintained until sacrifice at week 60. Although prostatitis and prostatic enlargement were frequently observed, especially in the TP group, numbers of atypical hyperplastic lesions were low and only one prostatic carcinoma in situ developed. Thus, despite the presence of proliferation, castration brought about a significant reduction in susceptibility to DMAB.

Aminobiphenyl Compounds↗

[Changes in cell cycle and RNA content in cultured cancer cells treated with cis-diamminedichloroplatinum (II)].

Recent reports have shown that CDDP interacts with RNA and protein as well as DNA. We studied the alteration of cell cycle, cellular RNA content and the effect of nucleic acid metabolism on cultured cancer cells after treatment with CDDP by flow cytometry and 3H incorporation assay. The alteration of cell cycle was found to be accumulation of cells in after delay S phase in cytostatic concentrations, CDDP inhibited 3H-TdR uptake markedly at this time and 3H-UR uptake earlier. Increase in RNA content accompanied accumulation of cells in G2M phase. This increase was not a specific phenomenon caused by CDDP, because increase in RNA content was also induced by other inhibitors of DNA synthesis. It is more likely that the direct alteration of cell cycle and cellular RNA content due to action of DNA-combined CDDP rather than that of RNA-combined CDDP.

Cell Cycle↗

[Studies of 5-FU concentrations associated with microangiography in colorectal cancer tissue].

In order to elucidate the effect of supplying vessels on 5-FU distribution within a tumor, the correlation between 5-FU tissue concentration and tumor microangiography was examined in 31 patients with colorectal cancer after administration of 5-FU (500 mg/day for 3 days). The 5-FU concentration at the tumor margin was significantly higher than that in the other two tissue areas (p less than 0.05). A low 5-FU concentration was noted in the central region of ulcerative cancer showing vertical invasion with vascular disarray and/or histological necrotic foci. This type of tumor also showed a low RNA index by flow cytometry. The present study indicates that the vascular change and vascular pattern of a tumor may be a major contributing factor to 5-FU transfer from the blood circulation into a tumor.

Adult↗

Strong promoting activity of reversible uracil-induced urolithiasis on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The tumor-promoting effect of uracil-induced calculi on rat urinary bladder carcinogenesis was investigated in male F344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Since uracil-induced calculi and papillomatosis of the bladder are reversible, uracil was given for a limited period after the treatment with BBN. Animals were given 0.05% BBN in their drinking water for 4 wk and then treated with uracil as 3% of the diet for 8 or 16 wk. After the uracil treatment, rats were given basal diet without uracil until Wk 28 of the experiment. Animals were killed from each group at the end of either Wk 12, 20, or 28. The incidence of carcinoma of the bladder was 40% after only 8 wk of uracil treatment following BBN initiation and increased to 100% when uracil treatment was extended to 16 wk. After discontinuation of uracil treatment, the papillomatosis disappeared, but the incidence of carcinoma steadily increased with increasing time. In the control group given BBN alone, only 1 of 16 rats had carcinoma at Wk 28. The present findings clearly demonstrate that uracil-induced urolithiasis had a strong promoting activity on BBN bladder carcinogenesis.

Animals↗

Different modifying response of butylated hydroxyanisole, butylated hydroxytoluene, and other antioxidants in N,N-dibutylnitrosamine esophagus and forestomach carcinogenesis of rats.

The modifying effects of antioxidants were examined in a carcinogenesis system after N,N-dibutylnitrosamine treatment. Male F344 rats were given 0.05% N,N-dibutylnitrosamine in their drinking water for 4 wk and then treated with basal diet containing 2% butylated hydroxyanisole (BHA), 1% butylated hydroxytoluene (BHT) with 7 ppm vitamin K, 0.8% ethoxyquin, 5% sodium L-ascorbate, 5% sodium erythorbate, or no added chemical for 32 wk. BHA enhanced forestomach carcinogenesis but did not enhance esophageal carcinogenesis. BHT enhanced esophageal carcinogenesis but did not enhance forestomach carcinogenesis. Ethoxyquin significantly enhanced esophageal tumorigenesis. Neither esophageal nor forestomach carcinogenesis was affected by the other antioxidants evaluated. BHA significantly increased DNA synthesis of the forestomach epithelium, whereas BHT tended to increase that of the esophageal epithelium. Thus, BHA and BHT showed different modifying responses in carcinogenesis of the esophagus and forestomach.

Animals↗

Lack of tumorigenic response in the prostate gland of castrated F344 rats by 3,2'-dimethyl-4-aminobiphenyl given with methyltestosterone.

In an attempt to induce a high incidence of prostate carcinoma, 3,2'-dimethyl-4-aminobiphenyl (DMAB), a prostatic carcinogen, was given during the period of cell proliferation of the prostate gland induced by the administration of methyltestosterone (MT) to castrated F344 rats. Three weeks after the surgical castration, rats were given diet containing 300 ppm of MT for 2 weeks and basal for 2 weeks alternately 12 times. During each treatment with MT, one (group 1) or two (group 2) subcutaneous injections of 50 mg/kg body wt. of DMAB was given. After the last treatment of MT, a pellet of testosterone propionate (TP) was implanted in the subcutis of all animals until the end of the experiment (week 60). No carcinomas developed in the prostate gland of any of the rats. Atypical hyperplasia of the ventral lobe of prostate was found in 4 of 22 rats in group 1 and 2 of 20 rats in group 2. The incidences of atypical hyperplasia of the seminal vesicles in groups 1 and 2 were 64% and 75%, respectively. No pathological lesions in the prostate were observed in 32 rats given DMAB without MT treatment.

9,10-Dimethyl-1,2-benzanthracene↗