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Biomedical subjects

K Yasuhara

Publications and source records attributed to K Yasuhara.

At least 19 recordsLinked to original sources
PubMed1995

Effect of thyroid stimulating hormone on the development and progression of rat thyroid follicular cell tumors.

Time course changes in cell proliferative activity of thyroid focal hyperplastic and tumorous lesions as well as blood thyroid-related hormones in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) were examined following chronic administration of 0.1% sulfadimethoxine (SM) in the drinking water for 1, 4, 8, 12 and 16 weeks and at the end of a subsequent 4-week recovery period. Serum thyroid stimulating hormone (TSH) levels increased rapidly from week 1 of SM treatment, reaching a peak at week 8, and then decreased gradually with prolongation of treatment period, although remaining significantly elevated as compared with the corresponding controls at all time points up to week 16. Follicular cell hyperplasias and adenomas of the thyroid occurred from week 4 and carcinomas from week 8. All of these lesions showed high cell proliferative activities corresponding to high serum TSH levels during the early stage, but the levels in hyperplasias and adenomas decreased rapidly with prolongation of SM treatment. After the recovery period, serum TSH levels had returned to below the normal range and cell proliferation in follicular hyperplasias and adenomas had stopped or was very low. Some carcinomas demonstrating invasive growth also showed remarkable decreases in the cell proliferative activity. The results of our study strongly suggest that a high serum TSH level plays an important role in the early stage of thyroid tumorigenesis and that some tumors exhibiting invasive growth are still dependent on TSH stimulation.

Animals↗
PubMed1995

Doppler velocity histogram analysis of hepatocellular carcinoma.

To study the characteristics of tumor blood flow, flow profiles from hepatocellular carcinomas (39 profiles) and normal hepatic arteries (23 profiles) were evaluated using velocity histograms obtained with Doppler ultrasound. The histograms were classified into three types: (1) high-peak, (2) flat, and (3) low-peak. Characteristically, the low-peak types and the flat types, with flows in opposing directions, were seen only in the tumor vessels. The turbulence in a phantom flow model was of the low-peak type. Spectral analysis revealed that the velocity profile of tumor blood flow was different from that of noncancerous flow and that tumor blood flow was characterized by turbulence.

Blood Flow Velocity↗
PubMed1994

Time course observation of thyroid proliferative lesions and serum TSH levels in rats treated with thiourea after DHPN initiation.

Time course changes in serum TSH and quantitative data for thyroid proliferative lesions in male F344 rats administered N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2000 mg/kg body weight, single s.c. injection) followed by 0.1% thiourea (TU), were assessed at weeks 1, 2, 4, 8, 12 and 16 of treatment. The serum T4 level in the TU group was markedly decreased at week 1 and remained significantly lowered throughout the experiment. Serum TSH levels, in contrast, were elevated up to a peak at around week 4 with a return to the normal range at week 12. Thyroid weights in the TU group were increased significantly in a treatment period-dependent manner. Histopathologically, marked hypertrophy of thyroid follicular cells occurred at the early stage of TU treatment. Proliferative lesions, such as hyperplasia and adenomas, occurred from weeks 2 and 4, respectively, and increased with the later treatment period. The cell proliferative activity of follicular cells, assessed by BrdU incorporation, was high until week 2, but then returned to normal. The initially appearing hyperplasias and adenomas were characterized by marked proliferation but this also greatly decreased at later stages when TSH was no longer elevated. The results of our study thus suggest that a high serum TSH level plays an important role in the early phase of thyroid tumorigenesis and 8 weeks treatment with test substances is sufficient for detection of thyroid tumor promoter potential in two-stage thyroid carcinogenesis models.

Adenoma↗
PubMed1994

Synergistic effects of phenobarbital and thiourea on proliferative lesions in the rat liver.

To evaluate the effects of phenobarbital (PB) and thiourea (TU), alone or in combination, on proliferative lesions of the liver, thyroid and lung, male F344 rats initiated with 2000 mg/kg body weight N-bis(2-hydroxypropyl) nitrosamine (DHPN) were given diet and/or drinking water containing 0% PB/TU (group 1), 1000 ppm PB (group 2), 0.1% TU (group 3) and 500 ppm PB and 0.05% TU (group 4), from weeks 2 to 20 for 19 weeks. Group 4 showed remarkable increases in the number of hepatocellular altered foci per animal, the values being superior to the averages of groups 2 and 3. The number of thyroid proliferative lesions per animal was highest in group 3 and lowest in group 2. Lung proliferative lesions were induced in all groups, but no modifying influence on their development was evident in the combined group. The present results indicate that combined administration of PB and TU exerts synergistic enhancing effects on hepatocarcinogenesis.

Animals↗
PubMed1994

Study on the carcinogenicity of tannic acid in F344 rats.

The carcinogenicity of tannic acid, a compound that is used as a food additive, a clarifying agent and a refining agent, was examined in F344 rats of both sexes. Tannic acid was dissolved in distilled water at concentrations of 0.25 and 0.5%. The doses were selected on the basis of results from a 13-wk subchronic study. Groups of 50 male and 50 female rats were given one of these solutions ad lib. as their drinking water for up to 2 yr. The mean body weights of the treated males were essentially comparable with those of the controls, whereas treated females had lower mean body weights than the control group. A variety of tumours developed in all groups, including the control group, but all the neoplasms were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Thus, it is concluded that, under the conditions of the experiment, tannic acid has neither carcinogenic potential in F344 rats nor modifying effects on spontaneous tumour development.

Administration, Oral↗
PubMed1994

Experimental induction of pulmonary fibrosis in Syrian golden hamsters by N-methyl-N-nitrosourethane.

A range finding study for experimental induction of pulmonary fibrosis in which female Syrian golden hamsters received five subcutaneous injections of 0.8, 0.6, 0.4, 0.2 or 0 mg of N-methyl-N-nitrosourethane (MNUR) once a week or once per two weeks revealed most of the animals of the 0.8 mg group to die of acute pulmonary injury due to MNUR while typical interstitial pneumonia was induced in the 0.6 mg group. Based on these results hamsters were given five subcutaneous injections of 0.6 mg/animal of MNUR once per two weeks and then reared without any treatment for 12 weeks. Marked interstitial edema and intraalveolar infiltration of macrophages due to alveolar capillary damage were seen in treated animals at week 1, and secondary diffuse fibrotic thickening of the alveolar septa, as evidenced by increased type III collagen demonstrated immunohistochemically, was marked thereafter. The content of hydroxyproline in the lung was significantly increased from week 4. The present study indicates that lung injuries attributable to primary damage of alveolar capillaries progress to diffuse alveolar fibrosis in hamsters treated with MNUR, suggesting that this animal model might be of advantage for pathogenetic analysis of the relationship between pulmonary fibrosis and lung cancer development.

Animals↗
PubMed1994

Thyroid proliferative lesions induced by anti-thyroid drugs in rats are not always accompanied by sustained increases in serum TSH.

To examine changes in serum TSH and determine whether the sustained excess is necessary for the development and/or progression of thyroid tumors, male F344 rats were administered drinking water containing thiourea (TU), at 0.1 or 0.05%, or sulfadimethoxine (SM), at 0.025 or 0.0125%, for one week in Experiment I. All of the treated animals showed decreased serum levels of T3 and T4 and an increased TSH. In Experiment II, male rats were given a s.c. injection of N-bis(2-hydroxypropyl) nitrosamine (DHPN:1500 mg/kg BW) and, starting one week later, received drinking water containing the same doses of TU or SM as in Experiment I for the following 20 weeks. Thyroid follicular proliferative lesions were induced in most rats treated with TU and SM. However, these treated animals did not demonstrate any consistent alterations in serum T3, T4 and TSH levels, except for the high dose TU group. The present studies thus suggest that thyroid tumors can grow even under conditions of fluctuating serum TSH levels during the progression phase, although TSH stimulation might be an absolute requirement in the early phase of tumor development.

Animals↗
PubMed1992

Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month.

The gelatin-starch syrup microencapsulation method was applied to subacute toxicity studies of tribromomethane (TBM), dibromochloromethane (DBCM) and bromodichloromethane (BDCM). Groups of Wistar rats (7 males and 7 females) both sexes were given diet containing microcapsules of each of these trihalomethanes (THMs) at the following concentrations: TBM, 0.068, 0.204 and 0.612% in males, and 0.072, 0.217 and 0.651% in females; DBCM, 0.020, 0.062 and 0.185% in males, and 0.038, 0.113 and 0.338% in females; BDCM, 0.024, 0.072 and 0.215% in males, and 0.024, 0.076 and 0.227% in females. Suppression of body weight gain was seen in each high-dose males fed TBM or BDCM and females fed DBCM or BDCM. Histopathologically, hepatic lesions such as vacuolization and swelling of liver cells were significantly noted in both sexes of all groups fed TBM, in both sexes of the middle- and high-dose groups fed DBCM, and in males of the high-dose group and in females of the middle- and high-dose groups fed BDCM. In addition, single cell necroses were observed in males and females fed DBCM and in males fed BDCM. Hepatic cord abnormalities were also noted in males of the high-dose group fed BDCM. Although no increases in serum transaminase activities (ASAT, ALAT) were evident in either sex fed any of the THMs, decreases in triglyceride content, cholinesterase and lactate dehydrogenase activity were observed. Renal lesions reported to occur in gavage studies were not found in the present feeding study. Lowest-observed-adverse-effect-level (LOAEL) of TBM and no-observed-adverse-effect-level (NOAEL) of DBCM and BDCM were determined to be 56.4 mg/kg, 18.3 mg/kg and 20.6 mg/kg, respectively, under the present experimental conditions.

Administration, Oral↗
PubMed1992

Chronic toxicity of microencapsulated bromodichloromethane administered in the diet to Wistar rats.

A chronic feeding study was carried out in Wistar rats using microencapsulated bromodichloromethane. The test substance was administered in the diet at doses of 0, 0.014, 0.055 and 0.22% for 24 months. Rats were sacrificed after 6, 12, 18 and 24 months of continuous dosing. The results showed a suppression of body weight gain in the 0.22% group for both males and females. Dose related changes were clearly observed in the liver with histopathological findings including fatty degeneration in the 0.014% or higher dose male groups, and fatty degeneration and granuloma in the 0.055 and 0.22% group females, as well as bile duct proliferation and cholangiofibrosis in the 0.22% group for both males and females. No significant differences in incidences or numbers of neoplastic changes were seen between control and any of the treatment groups. There were no dose-related non-neoplastic lesions in the kidneys of either sex. Lowest-observed-adverse-effect-level was determined to be 6.1 mg/kg/day under the present experimental conditions.

Animal Feed↗
PubMed1991

[Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate (TCEP) applied to female mouse skin].

Tris(2-chloroethyl)phosphate (TCEP), a widely used flame retardant, was tested for its skin chronic toxicity/carcinogenicity using female Slc: ddY mice. TCEP (5 and 50%) dissolved in ethanol was applied to the shaved skin twice a week for 79 weeks. The control group received ethanol under similar condition. In addition, 5 animals in each group were killed at 6 and 12 months and used for the chronic toxicity study. In body weight, food consumption and survival rate, there was no significant difference between the control and treated groups. Spleen weight was decreased in the 50% group. No significant difference in the incidence of tumors and other non-neoplastic lesions of the skin and other organs was found between the control and treated groups. The results indicate that under the conditions of the present study, TCEP has no carcinogenicity and toxicity for the skin.

Administration, Topical↗
PubMed1991

[Comparative studies on acute toxicity of glutaraldehyde using young and old rats].

Acute oral toxicity test of glutaraldehyde (GA) was carried out in young (5-6W) and old (57-60W) Wistar/ST rats. Experiment 1: Various doses of GA were administered by gavage. After 30 minutes, the rats showed abnormal gait, then took an abdominal or lateral position after 4 hours. Gross erosion, discoloration and thickening of the glandular stomach mucosa and hyperemia of the liver, intestine and lung were observed in the dead rats. The LD50 values were 283 mg/kg for young rats and 141 mg/kg for old rats. Experiment 2: One half of the LD50 doses (140 mg/kg and 70 mg/kg of GA) were administered to young and old rats by gavage, respectively. Both groups showed a similar toxicity. Organ weights were not changed. In gross findings, erosion, discoloration and thickening of the glandular stomach mucosa were observed on day 1-7, but these damages were recovered by day 14. Histopathologically, atrophy, degeneration, necrosis, hemorrhage, edema and cell infiltration of the glandular stomach mucosa were found on day 1. Recovery from these changes was observed from day 3. Changes in several serum enzyme activities were observed on day 1-3. Therefore, susceptibility to the acute toxic effect of GA was higher in old rats than in young rats. However, no apparent differences were observed in the toxic profiles by GA between young and old rats.

Administration, Oral↗
PubMed1988

Pulsed Doppler in the diagnosis of small liver tumours.

Doppler ultrasound detection of the blood flow associated with liver tumours was studied in primary hepatocellular carcinoma as well as in metastatic liver cancer and haemangioma. Doppler signals were detected from 48 of 55 hepatocellular carcinomas (87.3%), seven of 25 metastatic liver cancers (28.0%) and four of 30 haemangiomas (13.3%). The waveforms of Doppler signals were divided into two types: the pulsatile wave, which was detected from hepatocellular carcinoma (in 35 of the 48 with Doppler signals) and metastatic liver cancer (in all seven with positive signals), and the continuous wave, which was seen from hepatocellular carcinoma (41 out of 48) and haemangioma (in all four with signals). In six patients with hepatocellular carcinoma who underwent transcatheter arterial embolization, the pulsatile wave detected before therapy disappeared immediately thereafter and it is possible that this type of wave originates from tumour vessels. In the study of small, hypoechoic, mass lesions appearing in liver cirrhosis, such signals were also demonstrated, even in eight of 10 small hepatocellular carcinomas less than 2 cm in diameter, whilst they were not detected from nine regenerative nodules related to cirrhotic change. In conclusion, the Doppler ultrasound method may be a useful technique in detecting blood flow within liver tumours and may offer the possibility of a differential diagnosis of small tumours.

Adult↗