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Biomedical subjects

K Yasuhara

Publications and source records attributed to K Yasuhara.

At least 19 recordsLinked to original sources
PubMed1997

New color Doppler technique for detecting turbulent tumor blood flow: a possible aid to hepatocellular carcinoma diagnosis.

We created a new imaging technique that detects and emphasizes turbulence, which is a characteristic of blood flow in hepatocellular carcinoma. We devised two indices that determine a characteristic tumor flow, the bi-directional and low-peak indices. In the phantom study, both indices of turbulence caused by a stenosis were much higher. In the clinical study, both indices were significantly higher in tumors than in the portal vein or hepatic vein. A turbulent blood flow was detected in 77% of tumors, whereas such detection seldom occurred in the portal or hepatic vein. This technique has the potential to distinguish turbulence in hepatocellular carcinoma.

Biopsy↗
PubMed1996

Promoting effect of large amounts of vitamin A on cell proliferation of thyroid proliferative lesions induced by simultaneous treatment with thiourea.

In order to examine modifying effects of simultaneous treatment with large amounts of vitamin A (VA) and thiourea (TU) on the thyroid tumorigenesis in rats, male F344 rats were initiated with N-bis(2-hydroxypropyl)nitrosamine (2800 mg/kg body weight, single s.c. injection), and starting 1 week later received diet containing 0.1% VA (VA group), drinking water containing 0.2% TU (TU group), 0.2% TU + 0.1% VA (TU + VA group) or tap water/basal diet (control group) for 19 weeks. Serum T3 and T4 in the TU and TU + VA groups were significantly decreased as compared to the control group, while serum TSH levels were remarkably increased. The ratios of T3 and T4 decrease and TSH increase in the TU + VA group were remarkably more pronounced than in the TU group. Thyroid neoplastic lesions were only induced in the TU and TU + VA groups. The multiplicity of intracapsular follicular cell proliferative foci in the TU + VA group was significantly increased as compared to the TU group value. Cell proliferation of hypertrophic and subcapsular follicular cells, as well as in hyperplasias, and neoplasias with adenomatous growth pattern was significantly higher in the combined treatment case than after TU alone. In the liver, centrilobular hypertrophy of hepatocytes was seen in the TU and TU + VA groups, this being especially marked in the latter group. In the combined group case the affected cells were strongly positive for GST-P antibody binding. The results of the present study suggest that cell proliferation of thyroid follicular cell proliferative lesions in rats is enhanced by strong TSH stimulation with simultaneous treatment of TU and large amounts of VA.

Adenoma↗
PubMed1996

Morphometric and immunohistochemical studies on atrophic changes in lympho-hematopoietic organs of rats treated with piperonyl butoxide or subjected to dietary restriction.

Changes observed in lympho-hematopoietic organs in rats given piperonyl butoxide may be attributable either to direct toxic effects or to undernutrition. Male F344 rats were therefore fed diet containing 2.5% piperonyl butoxide or subjected to a 64% restriction of food intake for 2 weeks. Marked inhibition of body weight gain, decreased white blood cell count, depletion of T/B lymphocytes in lymphoid tissues, hypoplasia of the bone marrow, and decreased proliferating cell nuclear antigen (PCNA) labeling indices in these tissues were seen in both dietary restriction and 2.5% piperonyl butoxide groups. The depletion of T lymphocytes in the thymus and spleen was stronger in the 2.5% piperonyl butoxide group, as indicated by PCNA labeling indices and image analysis of T lymphocyte areas of the spleen, however, the toxicological profile observed for the chemically treated group was essentially the same as for animals on the restricted diet. These results suggest that the lympho-hematopoietic findings in rats receiving 2.5% piperonyl butoxide are probably due to undernutrition resulting from a reduced food intake.

Animals↗
PubMed1996

Ultrastructure and cell proliferative activities of karyomegalic alveolar epithelial cells in early pulmonary inflammatory lesions of Syrian golden hamsters induced by N-methyl-N-nitrosourethane.

To clarify the biological behavior of karyomegalic alveolar epithelial cells induced by N-methyl-N-nitrosourethane (MNUR) and whether these cells progress to lung tumors, female Syrian golden hamsters, 6 weeks old, were given five subcutaneous injections of 0.6 mg/animal of MNUR at two week intervals and their lungs were examined at weeks 1, 4, 8 and 12 after the termination of treatment. At week 1, in severely affected areas where marked multifocal thickening of alveolar walls due to interstitial edema and cellular infiltration was observed, some regenerative alveolar epithelial cells had abundant eosinophilic cytoplasm and gigantic bizarre nuclei. The cells were confirmed ultrastructurally to be derived from alveolar type II cells. The number of these karyomegalic epithelial cells became significantly decreased thereafter, together with the reduction of inflammatory changes. On AgNOR staining, normal alveolar epithelial cells had 1.8 +/- 0.03 black dots within their nuclei while the karyomegalic epithelial cells had 4 black dots or more, from 1 week. The PCNA labeling index of the karyomegalic epithelial cells at week 1 was 14.6 +/- 2.4, and was significantly decreased from 4 week. This epithelial cell population also displayed a wider range of DNA contents (2.1-5.5C) than normal epithelial cells (1.6-2.3C). These results suggest that karyomegalic alveolar epithelial cells may be mutant cells which occur after initiation with MNUR, but the possibility that they can act as progenitors of alveolar epithelial cell tumors was considered to be extremely low.

Animals↗
PubMed1996

[Continuous systemic venous oxygen saturation monitoring immediately after Fontan procedure].

Changes in cardiac output (CO), systemic venous oxygen saturation (SvO2), systemic oxygen consumption, and urinary output immediately after Fontan procedure were measured in 10 patients at the intensive unit (ICU) to assess the effects of aorusal from anesthesia, hypothermic management, and respiratory condition. The measurements were taken at the following phases; phase A in deep sedation under hypothermia (33-35 degrees C rectal temperature) and controlled ventilation; phase B in mild sedation under normothermia and controlled ventilation; phase C when awake under normothermia and assisted ventilation; phase D when awake under assisted ventilation; phase D when awake under normothermia immediately after extubation; and phase E 24 hours after extubation. Oxygen delivery (O2 Del.) and fractional oxygen fractions were calculated in each phase. Two patients whose SvO2 values were below 55% during the postoperative course needed reoperation for atrioventricular valve regurgitation in one case for PV stenosis in the other case. CO increased significantly (p < 0.05) after extubation (phase D), compared with that of controlled ventilation (phase B). Under hypothermia (phase A), urinary output was relatively higher with lower CO. There was a significant correlation between SvO2 and CO (R = 0.61) in phase A, however there was no correlation in phase E. Fractional oxygen extraction in phase A was significantly lower than in phase B. In conclusion, the continuous SvO2 measurements reflected real-time changes in cardiac output in the immediate post-Fontan patients. Induced hypothermia was beneficial in increasing urinary output presumably through the correction of maldistribution of cardiac output in post-Fontant patients. Arousal from anesthesia and spontaneous ventilation seemed advantageous for increasing cardiac output, hence, early extubation should be encouraged in the management of post-Fontan patients.

Blood Gas Monitoring, Transcutaneous↗
PubMed1996

Reproductive and developmental toxicity studies of toluene. II. Effects of inhalation exposure on fertility in rats.

Male and female Sprague-Dawley rats were exposed to toluene vapor at 600 and 2000 ppm for 6 h/day, and effects on their fertility were investigated. Females were exposed from 14 days before mating until day 7 of gestation. Males were exposed for a total of 90 days, including the mating period; treatment was begun 60 days before pairing, and toxicity with respect to testicular and reproductive functions was examined. In females of the 2000 ppm-treated group, salivation and lacrimation that may have been caused by CNS depression were observed starting 20 days after exposure. Although no abnormalities were seen in mating behavior or fertility, fetal mortality and the number of dams with dead fetuses increased in the 2000 ppm group. In the males exposed to 2000 ppm toluene for 90 days, an increase in kidney weights and a decrease in thymus weights were observed. Basophilic changes and necrosis of kidney tubules were greater at the higher exposure level. Additionally, decreases in the weights of the epididymides and spermatic count were observed, indicating toxicity of toluene to the male reproductive system in vivo for the first time. In conclusion, embryo-fetal toxic effects were apparent in female rats exposed to toluene before and during the early stage of pregnancy. Subacute exposure to a high level (2000 ppm) of toluene vapor elicited mild toxic changes in the kidneys, thymus, and reproductive organs of males. Toxic effects on fertility and reproduction were thus demonstrated not only in females but also in males exposed to toluene vapor in the present study.

Administration, Inhalation↗
PubMed1996

[Intensity of liver tumor promotion effects in rats given repeated oral administrations of benzimidazole compounds].

Liver tumor-promoting effects of anthelminthic agents, febantel (Feb), fenbendazole (Fen) or oxfendazole (Oxf), were investigated in a rodent 2-stage carcinogenesis model. Five-week-old male F344 rats were initiated with or without diethylnitrosamine (DEN) and one week later given diet containing Fen (3600, 1800, 600, 200 or 70 ppm), Feb (2000, 1000, 500 or 100 ppm) or Oxf (500, 250, 100 or 10 ppm) for 8 weeks. Induction of CYP1A1/2 was observed in treated groups of DEN + Feb and DEN + Oxf groups, and its induction was most marked in DEN + Oxf groups. CYP2B1 and CYP4AI were also induced in these treated groups. The number or area of Cx32 positive spots per hepatocyte was significantly decreased in treated groups except for DEN + Oxf 100 ppm group, as compared to DEN alone group. GST-P positive foci was significantly increased in DEN + Fen groups treated with 1800 ppm or more, DEN + Feb groups treated with 1000 ppm Feb or more and DEN + Oxf groups treated with 250 ppm Oxf or more. These results suggest that these three compounds have liver tumor promotion effects and the promoting action in Oxf is most strong among them.

Administration, Oral↗
PubMed1996

[Modifying effects of goitrogens on the tumor development in the liver and lung of rats].

In order to investigate whether goitrogens and liver enzyme-inducers modify the tumorigenesis in the liver or lung, 6-week old male F344 rats were given single subcutaneous injection of DHPN, and starting one week later received water containing goitrogens, namely sulfadimethoxine (SDM), propylthiouracil (PTU) and potassium thiocyanate (KSCN), or an enzyme-inducer, phenobarbital (PB), for 19 weeks ad libitum. Although the number of GST-P positive foci in the liver was significantly increased in the PB group as compared to the control group, there were no significant fluctuations in the SDM, PTU and PB groups. With respect to the lung, it is suggested that SDM, KSCN and PB may enhance the lung tumorigenesis, since the multiplicities of hyperplasias of alveolar epithelia were increased in groups treated with these compounds.

Animals↗
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↗
PubMed1995

Morphological evaluation of cyclophosphamide testicular toxicity in rats using quantitative morphometry of spermatogenic cycle stages.

The testicular toxicity of cyclophosphamide (Cp) in rats was evaluated by quantitative morphometry of spermatogenic cycle stages. Nine-week-old male Sprague-Dawley rats in Group 1 were given a single oral administration of 100 mg/kg of Cp, and were sacrificed at 1, 7, 14 and 21 days thereafter. Rats in Group 2 were orally given 100 mg/kg/day of Cp for 2 days, followed by 50 mg/kg/day for the next 3 days, and were sacrificed at 1 and 4 days after the last administration. The numbers of seminiferous epithelia were counted in the seminiferous tubules of stages II, V, VII and XII of the spermatogenic cycle. The data were expressed as numbers of spermatogenic cells per Sertoli cells per seminiferous tubule cross section. Animals in Group 1 showed decreased preleptotene spermatocytes at Day 7, decreased zygotene spermatocytes at Day 14, and decreased pachytene spermatocytes at Day 21. In group 2, testicular toxicity could also be clearly detected by this morphometric approach. The present morphometric study thus indicates that testicular toxicity can be detected from Day 7 even after a single administration of Cp.

Animals↗
PubMed1995

[Cell proliferative activities of cholangiofibrosis induced in rats treated with bromodichloromethane].

To clarify whether bromodichloromethane (BDCM)-induced cholangiofibrosis progresses to cholangiocarcinoma, further morphological examinations were performed on the livers obtained from our previous experiment. The livers of Wistar rats fed diet containing 2200, 550, 140 or 0 ppm of microencapsulated BDCM up to 24 months were examined at months 6, 12, 18, and 24. The liver sections were stained with H-E, PAS and Azan, and were subjected to immunostaining using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody for determination of the PCNA labeling index of bile duct epithelia, as well as silver staining for nucleolar organizer regions (AgNORs). At month 6, the severity of hyperplasia of atypical bile duct epithelia in the 2200 ppm group was marked, their PCNA labeling index being highest (68.5). The number of bile ducts gradually decreased, and the severity of fibrosis became more marked, with prolongation of the treatment. The PCNA labeling index in hyperplastic bile ducts in this group also decreased to 31.5 at month 24. The number of AgNORs in the nuclei of bile duct epithelia in the 2200 ppm group was highest at month 6, but decreased thereafter. The present study suggests that the possibility of the progression from cholangiofibrosis to neoplastic lesions is extremelly low.

Administration, Oral↗
PubMed1995

[Toxicity in rats fed diet containing iron lactate for 26 weeks].

In order to characterize the toxicity of iron lactate, a 26-week feeding study was performed in male and female F344 rats. Animals were divided into 2 groups, and given diet containing iron lactate at concentration of 0 or 2%. No animals died during the administration period. Body weight gain was suppressed in both sexes of the 2% group compared with the 0% group. Hematologically, anemia was observed in male of the 2% group. Serum alkaline phosphatase decreased in both sexes of the 2% group. The spleen weight of both sexes and kidney weight of females were higher in the 2% group than in the 0% group. Lipid peroxide increased not only in the liver and the kidney homogenates of treated males and females, but also in the serum of treated females. Histopathologically, iron deposition was observed in the liver, the kidney and the spleen of treated males and females, and in the intestine of treated females. The present results indicate that the iron lactate administration caused iron deposition in the liver and the other several organs, resulting in lipid peroxidation in these organs.

Administration, Oral↗
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↗