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Biomedical subjects

K Furuta

Publications and source records attributed to K Furuta.

At least 127 records · Page 7Linked to original sources

Possible infectious causes in 651 patients with acute viral hepatitis during a 10-year period (1976-1985).

Six hundred and fifty-one patients with acute viral hepatitis were identified serologically between January 1976 and December 1985. Of these, 109 (17%) had hepatitis A, 135 (21%) had hepatitis B, and 407 (62%) had hepatitis non-A, non-B. The possible infectious causes for acquisition of viral hepatitis occurring within 6 months before the onset of hepatitis were analysed. Approximately 80% of cases of hepatitis A and 70% of hepatitis B had no known risk factor, while in 67% of cases of hepatitis non-A, non-B possible risk factors for infection were documented. Infectious causes for hepatitis A were ingestion of raw shellfish (11%) and previous familial contact with patients with hepatitis A (10%). For hepatitis B, risk factors included medicare (24%), such as transfusion, surgical operation, accidental needle stick and acupuncture, and sexual contact (6%). For hepatitis non-A, non-B, the most important infectious cause was medical procedures (65%). The numbers of hospital employees were 2 (2%) with hepatitis A, 15 (11%) with hepatitis B and 14 (3%) with hepatitis non-A, non-B. These data suggest that hepatitis non-A, non-B can be a kind of nosocomial disease.

Acupuncture Therapy↗

Glandular changes associated with the spontaneous interstitial cell tumor of the rat testes.

Testes of untreated F344 and Wistar rats in the control groups of carcinogenicity studies were histologically examined, and the histopathological characteristics and histogenesis of glandular changes in these testes were studied. In 266 testes of 2-year-old F344 rats, 263 had interstitial cell tumors (ICTs) (98.9%) and 39 had glandular changes (14.7%). These glandular changes were also found in 1 out of 38 1-year-old F344 rat testes (2.6%), and 3 in 154 2-year-old Wistar rat testes (1.9%). The changes were observed exclusively in the interstitial cell tumors (ICTs). These glandular changes showed variation in size, shape and number. They were composed of tubules or cysts lined by a layer of cuboidal or columnar epithelial cells, which had terminal bars, occasionally PAS- and alcian blue-positive brush borders, and rarely, alcian blue-positive cytoplasmic vacuoles. Serial sections revealed that the changes were not connected with the rete testes, but with the degenerative seminiferous tubules involved in the ICTs lined by a layer of flat endothelial-like cells. The findings suggest that the lesions constitute metaplastic changes of the Sertoli cells.

Animals↗

Experimental induction of ovarian Sertoli cell tumors in rats by N-nitrosoureas.

Spontaneous ovarian tumors are very rare in ACI, Wistar, F344 and Donryu rats; the few neoplasms found are of the granulosa/theca cell type. Ovarian tumors were also rare in these strains of rats when given high doses of N-alkyl-N-nitrosoureas continuously in the drinking water for their life-span; however, relatively high incidences of Sertoli cell tumors or Sertoli cell tumors mixed with granulosa cell tumors were induced in Donryu rats after administration of either a 400 ppm N-ethyl-N-nitrosourea solution in the drinking water for 4 weeks or as a single dose of 200 mg N-propyl-N-nitrosourea per kg body weight by stomach tube. Typical Sertoli cell tumors consisted of solid areas showing tubular formation. The tubules were lined by tall, columnar cells, with abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented, round nuclei, resembling seminiferous tubules in the testes. In some cases, Sertoli cell tumor elements were found mixed with areas of granulosa cells. The induction of ovarian Sertoli cell tumors in Donryu rats by low doses of nitrosoureas may provide a useful model for these tumors in man.

Animals↗

Long-term studies on carcinogenicity and promoting effect of phenylbutazone in DONRYU rats.

The carcinogenicity and promoting effect of phenylbutazone were investigated in inbred DONRYU rats. In the carcinogenicity study, both sexes were administered the chemical at dietary levels of 0 (control), 0.125, or 0.25% for 2 years. Toxic lesions were associated with phenylbutazone treatment in the kidney and digestive tract, appearing to have an adverse effect on life expectancy. Various tumors were detected in all groups including the controls. With the exception of pheochromocytoma in the female high-dose group, no statistically significant increase in yield of any tumors, including leukemia, was apparent in the treated groups of either sex when the data were analyzed by Fisher's exact probability and/or chi-square tests. Application of an age-adjusted statistical analysis revealed a slight positive effect regarding the occurrence of pheochromocytomas, neoplastic liver nodules, and leukemias in females. However, these tumors are commonly observed to develop spontaneously in this rat strain, and no such effect was apparent in the male groups. In addition, no differences in incidences of relevant preneoplastic lesions were evident between control and treated groups. Thus phenylbutazone showed no carcinogenic activity in DONRYU rats when given continuously in the diet for 2 years. For the investigation of promoting effect, phenylbutazone was given as a dietary supplement for 2 years subsequent to initiation with N-ethyl-N-nitrosourea or N-propyl-N-nitrosourea. No enhancement of nitrosourea-induced leukemogenesis was apparent, although a slight promoting effect was demonstrated for renal and thyroid tumorigenesis.

Adrenal Gland Neoplasms↗

Induction of Sertoli cell tumors in the rat ovary by N-alkyl-N-nitrosoureas.

Relatively high incidences of Sertoli cell tumors of the ovary were induced in Donryu rats given a 400 ppm N-ethyl-N-nitrosourea solution as drinking water for 4 weeks or a single dose of 200 mg/kg N-propyl-N-nitrosourea by stomach tube. Typical Sertoli cell tumors were composed of solid areas showing tubular formation. Tubules were lined by tall, columnar cells having abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented round nuclei. In some cases, Sertoli cell tumors were found to be mixed with granulosa cell tumors.

Animals↗

Lack of carcinogenicity of triethanolamine in F344 rats.

The carcinogenic potential of triethanolamine was examined in F344 rats. Triethanolamine was dissolved in distilled water at levels of 0 (control), 1, and 2%, and groups of 50 males and 50 females were given these doses ad libitum as drinking water for 2 yr. The dose levels in females were reduced by half from wk 69, because of associated nephrotoxicity. A variety of tumors developed in all groups, including the control group, and all tumors observed were histologically similar to spontaneous tumors in this strain of rats. No statistically significant increase of the incidence of any tumor was observed in the treated groups of both sexes by the chi-square test. In this study, however, there was an increase in nephrotoxicity, which appeared to have an adverse effect on the life expectancy of the treated animals, especially of females. Therefore, an age-adjusted statistical analysis on incidences of main tumors or tumor groups of both sexes was also done by methods recommended by Peto et al. (1980). The result showed that a positive trend (p less than 0.05) was noted in the occurrence of hepatic tumors (neoplastic nodule/hepatocellular carcinoma) in males and of uterine endometrial sarcomas and renal-cell adenomas in females. These tumors, however, have been observed spontaneously in this strain of rats, and their incidences in the control group of the present study were lower than those of our historical controls. These results may indicate that a positive trend in the occurrence of these tumors is not attributable to triethanolamine administration. Increased incidence of renal tumors in the female high-dose group may have been connected with renal damage. Histological examination of renal damage observed in the treated groups, especially in the female high-dose group, revealed acceleration of so-called chronic nephropathy. In addition, mineralization of the renal papilla, nodular hyperplasia of the pelvic mucosa, and pyelonephritis with or without papillary necrosis were also observed. Thus, it is concluded that under these experimental conditions triethanolamine is not carcinogenic in F344 rats but is toxic to the kidneys.

Animals↗

Carcinogenicity of N-alkyl-N-(1-hydroperoxyalkyl) nitrosamines after intravenous injections in F344 rats.

As model compounds of alpha-hydroxy N-nitrosamines, four alpha-hydroperoxy N-nitrosamines were tested for their carcinogenic potential in F344 rats by i.v. injections. Correlation between chemical structure and carcinogenic potencies with respect to target organs was examined. Compounds used in this study were N-methyl-N-(hydroperoxymethyl)nitrosamine (MHPMN), N-ethyl-N-(1-hydroperoxyethyl)nitrosamine (EHPEN), N-propyl-N-(1-hydroperoxypropyl)nitrosamine (PHPPN) and N-butyl-N-(1-hydroperoxybutyl)nitrosamine (BHPBN). All chemicals were dissolved in distilled water and rats received 10 X 1 weekly i.v. injections of these chemicals (10 X 1 weekly injection of 5 mg/kg of MHPMN or equimolar amounts of other chemicals). Lung tumors were detected in all groups of both sexes and the incidences were 100% in each group. Thyroid tumors were also observed with relatively high incidences in treated groups except BHPBN. In the control group, tumors were observed mainly in the testis or uterus, and only two lung tumors and one thyroid tumor were observed in females. Histologically, all lung tumors in the MHPMN group were adenocarcinomas, squamous cell carcinomas or a mixture of both types. In the EHPEN, PHPPN and BHPBN groups, especially in females, incidences of carcinomas decreased as the length of the alkyl chain of the compounds, and most of lung tumors in females of the PHPPN and BHPBN groups were adenomas. Many of the thyroid tumors observed in the treated groups were follicular adenomas/carcinomas, whereas C-cell adenomas were the most common type of spontaneous thyroid tumors in this strain of rats. These target organs were similar to those of alpha-acetoxy N-nitrosamines reported previously. The results indicate that the carcinogenic activities of these chemicals depend on the length of the alkyl chain and that organ specificity of these chemicals may differ from those of their mother compounds.

Animals↗

Spontaneous neoplastic and non-neoplastic lesions in aging Donryu rats.

Spontaneous neoplastic and non-neoplastic lesions in 95 male and 96 female Donryu rats which were observed up to 120 weeks of age, were examined. The incidence of spontaneous tumors was 73.7% in males and 88.5% in females. In males, the most frequent tumors were pituitary adenomas, followed by pheochromocytomas and insulinomas. In females, uterine adenocarcinomas, mammary fibroadenomas and pituitary adenomas were the most common. Other tumors with relatively high incidences in both sexes included cortical adenomas of the adrenal gland, histiocytic sarcomas of the hematopoietic organs and granular cell tumors of the brain. Various tumors were also found in many other organs and/or tissues, although their incidences were low. The organ distribution and incidences of spontaneous tumors observed in Donryu rats were different from those in other strains of rats such as the ACI, Wistar, F344 or Sprague-Dawley strains. The main non-neoplastic lesions were observed in the lung, cervical lymph nodes and kidney of both sexes. In addition, lesions were also observed in the urinary bladder, prostate and peripheral nerves (spinal nerve roots and peripheral nerves) and/or femoralis muscle of males. Histologically, the most characteristic lesion was radiculoneuropathy with degeneration of the peripheral nerves.

Aging↗

Effect of Nocardia rubra cell wall skeleton and/or cyclophosphamide on leukemogenesis induced by N-ethyl-N-nitrosourea in Donryu rats.

The effect of Nocardia rubra cell wall skeleton (N-CWS) and/or cyclophosphamide (CP) on chemical carcinogenesis was examined in female Donryu rats exposed to N-ethyl-N-nitrosourea (ENU) in the drinking water for 6 weeks. Five administrations of N-CWS following ENU treatment caused a slight prolongation of the average survival of rats but did not reduce the incidence of leukemia. CP given on two occasions after ENU treatment caused a moderate prolongation of average survival period and a moderate reduction of the incidence of leukemia, but significant differences from ENU-treated control group values were not observed after statistical analysis. Combined treatment with N-CWS and CP after ENU treatment caused prolongation of the average survival period of rats and a statistically significant reduction in the incidence of leukemia. The present experiment indicates that combined treatment with N-CWS and CP effectively reduces induction of leukemia by ENU in rats, although other types of tumors were not affected.

Animals↗

Organ-specific carcinogenicity of N-methyl-N-nitrosourea in F344 and ACI/N rats.

Male and female F344 rats were continuously administered N-methyl-N-nitrosourea (MNU) in their drinking water at concentrations of 200 or 100 ppm, and both sexes of ACI/N rats were given MNU at a concentration of 200 ppm. By the 42nd week of the experiment, high incidences of brain/spinal cord tumors were observed in both strains of rats. Histologically, many of them were astrocytomas or anaplastic astrocytomas. In addition, malignant neurinomas were also detected in the spinal nerve roots and trigeminal nerves, although their incidences were rather low. There was no difference in the type and incidence of these neurogenic tumors between the two strains of rats. Tumors of the tongue and esophagus were mainly observed in the high-dose group of F344 rats and those of the glandular stomach were observed in the low-dose group of F344 rats. In ACI/N rats, tumors of the heart and renal pelvis were detected. The organ-specific carcinogenicity of MNU in these two strains of rats was compared with that of MNU in Donryu rats. It was demonstrated that organ specificity of MNU given orally was influenced not only by the strain of rats but also by the dose level.

Animals↗

Lack of evidence of carcinogenicity of technical-grade piperonyl butoxide in F344 rats: selective induction of ileocaecal ulcers.

The carcinogenicity of technical-grade piperonyl butoxide was studied in F344/DuCrj rats fed a dietary level of 0.5 or 1% for 2 yr. Various tumours were detected in all groups, including the untreated control group, but no significant dose-related increase in the incidence of any tumour was found. Thus, it is concluded that under these experimental conditions piperonyl butoxide was not carcinogenic in F344 rats. Unexpectedly, however, ileocaecal ulcers were found in animals of both sexes in both experimental groups and the incidence was dose related. Further studies are required to establish the mechanism of induction of ileocaecal ulcers by piperonyl butoxide.

Administration, Oral↗

A possible explanation for a greater discrepant suppression by adenosine and N6-cyclohexyl adenosine of the guinea-pig ileal contraction.

Adenosine and N6-cyclohexyl adenosine (CHA) reduced dose-dependently a twitch contraction of guinea-pig ileum and their IC50 values were 1.0 X 10(-5) and 1.1 X 10(-8) M, respectively. By exposure to adenosine uptake and deaminase inhibitors, dipyridamole and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), the adenosine-induced inhibition was enhanced, whereas the CHA-induced one was almost unchanged. Therefore, outstanding potency difference of the suppression by adenosine and CHA was minimized by concurrent addition of both the inhibitors. Uptakes of [3H]CHA into the guinea-pig ileum and taenia-coli were considerably lower than those of [3H]adenosine and were insensitive to dipyridamole. In the rat connective tissue segment, uptake of [3H]adenosine was smaller than that in the guinea-pig taenia-coli and ileal segments (especially, in the latter), and was virtually unaffected by 10(-5) M dipyridamole. These findings suggest that a greater discrepancy of the suppression by adenosine and CHA of the ileal twitch may substantially result from their different uptake and deamination in the synaptic region rather than their dissimilar intrinsic activity for the purinoceptor.

Adenosine↗

Relation between development of leukemia and duration of N-nitroso-N-ethylurea treatment in DONRYU rats.

N-Nitroso-N-ethylurea (NEU; CAS: 759-73-9) is a strong leukemogen that induces erythroblastic leukemia in inbred DONRYU rats. In the present experiments, relationships between development of leukemia, duration of NEU treatment, and sequential changes in the hematopoietic organs during carcinogen administration were examined. In experiment 1, groups of rats were given a 400-ppm NEU solution for 0, 2, 4, 6, 8, or 10 weeks, and the resultant incidence of leukemias was 0, 26, 40, 75, 95, and 100%, respectively. Of the various types of leukemia, the erythroblastic type was observed in 0, 0, 20, 40, 95, and 90% of rats, respectively. The average latent period showed an inverse correlation with the duration of NEU treatment. In experiment 2 the animals were divided into carcinogen-treated and control groups, and rats were sacrificed periodically for histopathologic examination. In the experimental group, the bone marrow became hypoplastic soon after commencement of NEU treatment and at the 6th week became severely aplastic, thereafter recovering slightly. At the 10th week, 2 rats out of 5 examined were leukemic. Relationships between incidence of leukemia, duration of NEU treatment, and sequential changes of the bone marrow during carcinogen administration are discussed.

Animals↗