[Open heart surgery without blood transfusion (author's transl)].
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Biomedical subjects
Publications and source records attributed to H Tsuda.
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The effect of azathiopurine and OK-432 on bladder carcinogenesis in rats was evaluated using the carcinogens, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT). Azathiopurine did not affect FANFT bladder carcinogenesis in any treatment. By contrast, when azathiopurine was fed simultaneously with BBN there was a significant increase in the incidence of bladder tumors, although it had no effect if administered before or after BBN. Short-term administration (8 weeks) of OK-432 subcutaneously before, during, or after BBN did not affect bladder carcinogenesis, but if OK-432 was begun after BBN and continued until the end of the experiment, the incidence of BBN-induced bladder tumor was significantly reduced. No bladder lesions were observed in control rats or in rats receiving only azathiopurine or OK-432.
The effect of vitamin A acetate on the urinary bladder carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was determined in male Wistar rats. Vitamin A acetate at the dose administered induced no changes in the urinary bladder or other organs when administered without the carcinogen. However, hypervitaminosis A inhibited keratinization and squamous metaplasia in bladder lesions induced by BBN, and the incidence of transitional cell carcinoma and papilloma of the urinary bladder was significantly reduced at a dose greater than 100 IU/g diet (P less than 0.02). The present experiment suggests that for the urinary bladder epithelium of rats hypervitaminosis A reduced susceptibility to the tumorigenicity of BBN.
As shown by results in this paper, NaNO2 induced endoreduplications and chromosomal aberrations as well as malignant transformation, in hamster cells in vitro, although the carcinogenic action of NaNO2 has not been reported in animals. The mode of action of NaNO2 in mammalian cells requires further investigation.
The addition of K2Cr2O7, at concentrations ranging from 0.1 to 0.5 microng/ml, to hamster total embryonic cells for 24 h, resulted in consistent and drastic chromosomal aberrations including gaps, breaks and exchanges. The above effect, however, was reduced successfully by the addition of a reducing agent, Na2SO3. Among other chromium compounds examined, divalent and trivalent chromium salts were ineffective on chromosome morphology even at a concentration of 3.5 microng/ml as chromium, whereas a hexavalent compound, CrO3, was highly effective. K2Cr2O7 also enhanced the morphological transformation rate in a short-term colony assay, in whicy hamster embryonic cells (1x10(4) cells/60-mm dish) were treated and the morphology was observed 8 to 10 days after the treatment.
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N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN), which selectively induced urinary bladder tumors in several experimental animal species, was found to cause damage of DNA in the bladder epithelium. Wistar strain rats were given 100 mg/kg of BBN intravesically and killed after 2, 6, 12, 24, or 48 hr. DNA damage was examined by measuring the change in sedimentation pattern in an alkaline sucrose gradient. Amount of DNA in each fraction was determined by fluorescence spectrophotometry. At 2 hr, the sedimentation profile shifted from heavier (No 15, control peak) to lighter (Nos. 2 approximately 4) fractions, and the maximum effect appeared at 6 hr as a single peak in the lighter fractions. At 12 hr, damaged DNA was in the process of repair as two peaks were present, one light and one heavy. At 48 hr, the sedimentation profile showed a single peak identical with that of controls indicating complete repair of DNA.
The effect of iodoacetamide or Tween 60 on carcinogenicity of methylnitrosocyanamide (MNC) in rats was examined. A significant increase in the incidence of the forestomach tumors (P less than 0.01) was observed in rats treated with MNC and iodoacetamide simultaneously. Moreover, there were 2 cases of glandular stomach tumors in rats treated with MNC and Tween 60 simultaneously. They were one well-differentiated adenocarcinoma and one polypoid hyperplasia. This result indicates that MNC under certain conditions is carcinogenic to the glandular stomach of rats in addition to the forestomach. Tween 60 might act by facilitating direct contact between MNC and the glandular stomach mucosa.
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This paper describes an unusual, familial bilateral papillary cystadenoma of the epididymis found in three siblings. The histological characteristics of the tumor were: 1) papillary proliferation of clear cells, consisting of both tall columnar and round ovoid cells, in the efferent duct epithelium; and 2) cystic dilatation of the duct with colloidal material. The present cases were unique in two respects: 1) familial bilateral papillary cystadenomas probably associated with Lindau's disease have not been reported previously: and 2) electron microscopic observations suggested that the tumors originated from the efferent duct.
Six groups of female outbred Wistar rats were subjected to the following treatments: 2,500 ppm 3-amino-1H-1,2,4-triazole (amitrole) administered in the drinking water (group I); partial thyroidectomy and administration of amitrole in the drinking water (group II); partial thyroidectomy plus autoimplantation of resected thyroid tissue plus administration of amitrole in the drinking water (group III); no treatment (control of group I) (group IV); partial thyroidectomy without amitrole administration (control of group II) (group V); or partial thyroidectomy plus autoimplantation of resected thyroid tissue without amitrole administration (control of group III) (group VI). Goiters developed in all rats given amitrole (groups I-III). Invasive growth of the proliferating follicular tissue through the capsule into adjacent fatty tissue and of pericapsular blood vessels was frequent in these groups (P less than 0.001); invasive lesions were more frequent in the lobectomized thyroid glands of rats (groups II and III). Seven papillary adenomas composed of atypical cells with hyperchromatic nuclei and many mitoses were found in the thyroid glands and grafts in amitrole-treated groups I-II. No invasive growth or adenomas appeared in the control rats of groups IV-VI. Cholangiofibrosis developed in 5 of 100 rats in groups I-III.
The object of this study was to determine the effects of individual amino acid supplements on the development of tyrosine toxicity in growing rats fed 10% casein containing 5% tyrosine. Each amino acid was added at levels equivalent to its content in 20% casein. Supplement of methionine to the high tyrosine diet partially alleviated both growth depression and pathological lesions. Threonine and cystine had a somewhat beneficial effect, but the single addition of other amino acids was not effective. Besides, some amino acids enhanced the severity of the toxicity even more. The effects of methionine supplementation were highest at 0.66 to 1.32% levels (equivalent to the methionine content in 20 to 40% casein). By the supplement of both 0.66% methionine and 0.90% threonine to the high tyrosine diet, growth was significantly improved and toxic lesions were completely prevented. It was confirmed that the counteracting effects to the toxicity, caused by the extra addition of protein (casein) to rats fed a high tyrosine-low protein diet, were mainly attributed to the effectiveness of the methionine and threonine, i.e., first-and second-limiting amino acids, respectively, contained in it.
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Histological types and grades of 613 urinary bladder cancers induced in rats by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) were analyzed. Most of them (95.1%) were transitional cell carcinomas, the remainder being squamous cell carcinomas (3.3%), undifferentiated carcinomas (2.5%), and carcinosarcomas (0.3%). Among the transitional cell carcinomas, 23.3% were Grade I anaplasia, 55.2% Grade II, and 21.5% Grade III. Among the squamous cell carcinomas, 20% each were Grade I and II, and 60% Grade III. Most of the undifferentiated carcinomas were Grade III. Some of the cases of transitional cell carcinoma had areas of squamous metaplasia and/or glandular metaplasia, and the incidence of metaplasia increased with the grade of anaplasia. Approximately 36% of the cases of transitional cell carcinoma were of the invasive type. Invasive types were twice as numerous among cases of squamous cell carcinoma as among those of transitional cell carcinoma and all of undifferentiated carcinomas were invasive. The incidence of invasive type was closely related to the grade of anaplasia. These results show that the morphological characteristics of urinary bladder carcinomas induced by BBN in rats are similar to those seen clinically in humans.