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Biomedical subjects

R Oyasu

Publications and source records attributed to R Oyasu.

At least 145 records · Page 8Linked to original sources

Ureterosigmoidostomy in rats: a model for the study of bladder tumour carcinogenesis and cocarcinogenesis.

A modified Coffey I ureterosigmoidostomy has been developed in rats as a model of urinary diversion for studying bladder carcinogenesis and co-carcinogenesis. Diverted and sham-operated animals were killed at 1, 3 and 6 months. Excretory urograms revealed minimal hydroureteronephrosis in most diverted animals. Upper tract bacterial colonisation was 9 times more frequent in diverted animals. Approximately one-third of the diverted animals had focal cortical scarring; however, renal function was normal in all groups as assessed by serum creatinine and electrolytes. These studies indicate that ureterosigmoidostomy in rats is a satisfactory model of urinary diversion for studying carcinogenesis.

Animals↗

Multiple autotransplantation of rat mammary induced by 7,12-dimethylbenz[a]anthracene: brief communication.

Mammary tumors induced in outbred Sprague-Dawley rats by 7,12-dimethylbenz]a]anthracene were excised, cut into 1- to 2-mm3 pieces, and then autotransplanted sc along the mammary line at six sites. Following an average period of 20--30 days, these autografts grew to approximately 2 cm in diameter in 32 of 48 rats (67%). Autografts in the other 33% of the rats remained dormant. Mammary tumors transplanted into allogeneic hosts failed to grow. Tumors derived from autotransplantation were indistinguishable from their primary tumors with respect to their histologic features, the nature of hormone dependency, the content of estrogen receptors, and their ability to incorporate [3H]leucine. Furthermore, autotransplanted tumors derived from a single primary tumor varied little with regard to the preceding parameters; thus they provided an opportunity for serial sampling of individual tumors for repeated morphologic and biochemical evaluations.

9,10-Dimethyl-1,2-benzanthracene↗

Induction of tumors in heterotopic bladder by topical application of N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine.

The heterotopic urinary bladder with a communicating reservoir is a potentially useful model for bladder carcinogenesis studies. As a test of whether such bladders will develop transitional cell carcinomas after chronic carcinogenic stimuli, two carcinogens, N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine, were instilled repeatedly into the reservoir connected with the heterotopic bladder. Transitional cell carcinomas developed in 25 of 33 heterotopic bladders exposed to cumulative doses of 1.5, 3.0, or 6.0 mg of N-methyl-N-nitrosourea for between 20 and 30 weeks, while heterotopic bladders exposed to cumulative doses of 150 or 300 mg of N-butyl-N-(3-carboxypropyl)nitrosamine failed to develop tumors. However, 11 of 27 rats with heterotopic bladders that were exposed to N-butyl-N-(3-carboxypropyl)nitrosamine for over 20 weeks developed tumors in their homotopic or natural bladders. N-Methyl-N-Nitrosourea probably acted directly on the bladder epithelial cells to induce neoplastic change. The reason(s) for the development of tumors in homotopic but not heterotopic bladders when N-butyl-N-(3-carboxypropyl)nitrosamine was administered directly into the heterotopic bladders could not be ascertained from these studies.

Animals↗

Metaplastic squamous cell carcinoma of bronchus simulating giant cell tumor of bone.

A 57-year-old man underwent a right pneumonectomy for a bronchogenic carcinoma following bronchoscopy and bronchial biopsy. The tumor was a polypoid mass arising from the lower lobe bronchus. Microscopically it was characterized by mononuclear cells mixed with randomly distributed multinucleated giant cells similar to those seen in giant-cell tumor of bone. Also found were portions showing typical squamous cell and spindle cell carcinoma. Based on the light and electron microscopic findings, we suggest that the current case represents a metaplastic squamous carcinoma showing mesenchymal cell differentiation. A hypothesis on the histogenesis of pleomorphic carcinomas was presented. The problems of histological diagnosis generated by such a tumor should be emphasized.

Bone Neoplasms↗

Absorption and protein binding of N-2-fluorenylacetamide and its metabolites in the bladder of rabbit.

To assess the reactivity of a bladder carcinogen, the absorption by the rabbit (male New Zealand White) bladder mucosa of N-2-acetylaminofluorene (AAF), N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF), and the N-O-glucuronide of AAF (N-OGI-AAF), as well as binding to the protein and RNA of bladder mucosa, was measured in vivo and in vitro. Mucosal pieces incubated for 3 hours in medium containing a carcinogen demonstrated that the fluorene nucleus of both AAF and N-CH-AAF bound equally with cellular proteins, while N-OGI-AAF binding was lower. In the presence of an excess of beta-glucuronidase, however, N-OGI-AAF showed binding equivalent to its metabolic precursor. After a 3-hour instillation into the bladder lumen of radioactive carcinogens suspended in urine in vivo, transmural absorption of AAF and N-OH-AAF (90%) was substantial, while N-OGI-AAF was absorbed less (55%). The renal excretion during this period varied from 18 to 52% of the instilled radioactivity. There was little reactivity of these carcinogens with the mucosal RNA, both in vivo and in vitro. The metabolism of N-OH-AAF and N-OGI-AAF was such, both in vitro and in vivo, that the acetyl group was not included in the final protein-carcinogen complex in what appeared to be an enzyme reaction.

2-Acetylaminofluorene↗

Human colon adenocarcinoma cells. II. Tumorigenic and organoid expression in vivo and in vitro.

A human colon epithelial tumor cell line (LS174T) recultured in vitro following passage through hamsters displayed differences in its cell doubling time and synthesis of carcinoembryonic antigen when compared with the cells grown solely in vitro. These animal-passaged cells more closely resembled the parent tumor cell line (LS180) derived from the primary tumor than LS174T, the trypsinized variant of LS180. Analysis of lactate dehydrogenase isoenzymes indicated that the tumor cells recovered from the hamsters were free of xenogeneic host tissue. Furthermore, LS174T grafted to athymic (nude) mice grew as a mucinous adenocarcinoma microscopically resembling the original tumor. The altered growth potential of LS174T was also demonstrated on confluent feeder monolayers of normal cells and by uninhibited multiplication in vitro. These results suggest that, at least in this one case, short-term passage of long-term cultured cells into xenogeneic hosts may effect a phenotypic reversion such that the cells regain properties observed in the primary tumor and the initial in vitro explant.

Adenocarcinoma↗

Suppression of dibutylnitrosamine-induced bladder carcinomas in hamsters by dietary indole.

Effect of dietary indole on the urinary bladder tumorigenesis by chronic dibutylnitrosamine (DBN) treatment was evaluated in hamsters. In the first experiment, in which DBN-water and diet were given ad libitum, dietary indole significantly suppressed bladder tumor incidence. The inhibitory effect was more pronounced in males. In the second experiment, in which consumption of both diet and DBN-water was rigidly controlled by pair-feeding, dietary indole again significantly suppressed bladder tumor incidence; its effect was similar in both males and females. This suppressive effect of indole on bladder tumorigenesis contrasted markedly with its failure to suppress tumors at other sites such as nasal sinuses, trachea, esophagus, and fore-stomach.

Administration, Oral↗

Biliary bacteria and hepatic histopathologic changes in gallstone disease.

This study attempts to assess the frequency and severity of liver damage in patients with gallstone disease and the role of bacteria in the development of these changes. Needle biopsy of the liver demonstrated acute inflammation of portal triads in 19 of 126 patients with gallstones, a finding not present in control patients. Acute inflammation occurred more often in patients with acute cholecystitis and choledocholithiasis than in chronic cholecystitis. Cultures of the biliary tract or liver were positive in 23 of 64 patients. The frequency of positive bile cultures increased with the severity of the biliary tract disease. Five out of 6 positive liver cultures were from patients with acute cholecystitis or choledocholithiasis. The data suggest that impairment of bile flow is responsible for the acute hepatic inflammatory changes.

Adolescent↗

Cell surface changes associated with malignant transformation of bladder epithelium in vitro.

Three properties of cell surface membranes of normal bladder epithelium and of two malignant urothelial lines transformed in vitro by Dr. Y. Hashimoto and Dr. H. S. Kitagawa were analyzed by means of morphological and chemical tools. Under scan electron microscopy, normal bladder epithelium displayed an appearance devoid of the pleomorphic, abundantly distributed, microvillous structures seen on the neoplastic cells. The molecular weight profiles of proteins dispersed from purified plasma membrane fractions demonstrated quantitative differences in the content of three molecular-weight classes between the native and the transformed cells. More striking differences were seen upon two-dimensional analysis of proteins solubilized from these two cell types, using 3 M KCl. These findings suggest that further investigations of the chemical moieties appearing on the cell surface early after transformation may enhance our understanding of proteins amenable for chemical and/or immunological attack to achieve control of the progression of bladder neoplasia.

Cell Line↗

Rheumatoid arthritis with rheumatoid heart disease and granulomatous aortitis.

Aortic insufficiency and aortitis are frequent complications of ankylosing spondylitis but are considered rare in rheumatoid arthritis. A 49-year-old woman with severe rheumatoid arthritis had the cardiovascular changes common to both diseases. At autopsy, the heart and aorta showed granulomatous ane fibrinous pericarditis and epicarditis, "core" granulomas in the aortic valve cusps and mitral valve leaflets, and coronary arteritis. These are considered to be classical changes of rheumatoid carditis. In addition, there were mesoaortitis with obliterative endarteritis of the vasa vasorum and fibrosis of the aortic cusps with separation of the commissures. These are considered to be changes of ankylosing spondylitis. This case, therefore, represents a mixed form of cardiovascular involvement within the spectrum of the rheumatoid diseases.

Aorta↗

Human colonic adenocarcinoma cells. I. Establishment and description of a new line.

A series of human colonic epithelial cell lines have been cultured from a single patient: LS-180 the original adenocarcinoma, LS-174T a trypsinized variant, and normal colonic tissue. The malignant cells, 20 to 40, mum in diameter and oval to polygonal, exhibited characteristics of normal colonic mucosal cells, namely, abundant microvilli prominent in secretory cells, and the presence of intracytoplasmic mucin vacuoles. The cultured adenocarcinoma cells, but not normal, demonstrated neoplastic properties by producing high levels of carcinoembryonic antigen (CEA) and by the ability to be propagated in hamster cheek pouches and in immunodeprived mice. The CEA production by the newly established line LS-180 released 900 times more CEA per cell into the culture medium and bore 30 times more cell-associated material than the established line, HT-29. These cell lines may permit detection of distinctive chemical, physiological, pharmacologic, and immunologic characteristics of neoplastic colonic cells.

Adenocarcinoma↗

Villous adenoma of the duodenum. A case report and review of the literature.

A case of villous adenoma of the duodenum, with focal in situ carcinomatous changes, has been described with a review of forty-two other case reports from the world literature. Occult bleeding, resulting in anemia, and vague obstructive symptoms appear to be the most common presenting findings. The average age was 56.4 years, which was seven years younger than the average age for villous tumors of the colon. Adequate radiologic studies should establish the diagnosis preoperatively. These tumors obtain relatively large size before causing significant symptoms. Approximately one third showed carcinomatous changes, and approximately one half of these were in situ changes. Local segmental resection for duodenal villous tumors is desirable when possible. However, in areas where this is not feasible, local mucosal excision is acceptable for benign tumors and for those with in situ carcinoma. If invasive carcinoma is found in the excised specimen, pancreatoduodenectomy is recommended. Insufficient evidence is available to adequately evaluate survival for malignant villous tumors of the duodenum, but the available data suggest that the survival after treatment of malignant villous tumors is comparable to other malignant lesions originating in the duodenum.

Adenoma↗

Suppressive role of indole on 2-acetylaminofluorene hepatotoxicity.

Indole is known to suppress the hepatotoxicity and carcinogenicity of 2-acetylaminofluorene (AAF) in rats and hamsters. For elucidation of the mechanism of its protective role, 2 experiments were conducted using young male rats. In the 1st experiment, the 24-hr biliary excretion of N-hydroxy-2-acetylaminofluorene (N-OH-AAF)-glucuronide was measured after 2 and 4 weeks of dietary administration of 0.03% AAF with or without 1.6% indole. The amount of [9-14C]N-OH-AAF that was excreted as the glucuronide following a single i.p. injection of [9-14C]AAF was lower after 2 weeks in animals fed AAF and indole, as compared to those fed AAF alone [1.5 +/- 1.2% versus 19.6 +/- 3.6% S.E. (p less than 0.001)]. After 4 weeks of AAF administration without indole, the biliary excretion fell to 4.8 +/- 2.1%. This was also significantly higher than that of the animals fed both AAF and indole [1.8 +/- 1.2% (p less than 0.025)]. The suppressive role of indole on the conjugate excretion was also reflected in a decreased biliary excretion of all [9-14C]AAF metabolites in animals treated with indole alone. In the 2nd experiment, the protective action of indole was assessed by survival following daily i.p. injections of N-OH-AAF and Na2SO4 solution. Na2SO4 increased the hepatotoxicity of N-OH-AAF. Indole suppressed the toxicity of N-OH-AAF even in the presence of Na2SO4. This protective role of indole was partially overcome only when excess sulfate was coadministered. These results indicate that indole suppresses the biliary excretion of the O-glucuronide of N-OHAAF during the initial exposure of the animal to the carcinogen, possibly reflecting decreased N-OH-AAF formation. Indole also modifies the metabolism of AAF FOLLOWING N-hydroxylation, perhaps activating N-OH-AAF, depending upon the concentration of sulfate available.

2-Acetylaminofluorene↗

Heterotopic urinary bladder with a communicating reservoir.

A heterotopic bladder attached to an Ommaya reservoir was transplanted to the back of a syngeneic rat. Following transplantation, the mucosa underwent ischemic necrosis. However, it was rapidly reepithelialized in 2 weeks as a result of spreading of the epithelium originating from the ureterotrigonal region. By light microscopy the regenerated epithelium was indistinguishable from the normal transitional epithelium, and the cannula connecting the reservoir to the bladder remained patent throughout the observation period of 22 weeks. One bladder, when examined at 22 weeks, contained a transitional cell papilloma with squamous metaplasia. Although further study is needed, this model is potentially useful in studies related to bladder carcinogenesis.

2-Acetylaminofluorene↗

Effect of pair-feeding of carcinogen on the incidence of bladder tumors in hamsters. Role of indole, age, and sex.

The role of indole in 2-acetylaminofluorene (AAF) bladder tumorigenesis was critically evaluated in hamsters. To avoid the influence of a nutritional factor on the tumor incidence, the animals were pair-fed for 8, 10, and 12 months. Addition of indole to the AAF diet resulted in a higher incidence of bladder tumors in both males and females (P less than 0.05, P less than 0.05). Indole definitely increased the bladder tumor incidence at 8 months (P less than 0.05). Also significantly different was the tumor incidence between males and females irrespective of the diet administered (P less than 0.05). Indole did not alter the urinary output of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) in males.

2-Acetylaminofluorene↗

In vitro interaction of estrogen and prolactin on hormone-dependent rat mammory tumors (38511).

Hormone-dependent, regressing mammary tumors in rats were incubated in a chemically defined culture medium containing tritium labeled leucine at 37 degrees for 2 hr. The rate of tritium incorporation into the protein fraction by these tissues was measured with and without the addition of 17beta-estradiol and/or ovine prolactin into the medium. Tumor tissue responded to either estrogen or porlactin by a 6-7% increase in the rate of 3-H-leucine incorporation. When the incubation medium contained both the hormones, the increase in the rate of 3-H leucine incorporation was 19% which was significantly greater than the sum of the effect of each single hormone measured independelntly. These results demonstrate a synergistic effect between estrogen and prolactin on rat mammary tumors.

Animals↗