Biomedical subjects
Publications and source records attributed to T Shoda.
We report a case of multiple sclerosis in which CT showed multiple ring-like enhancement and butterfly-like distribution of a low density area with marginal enhancement. The latter finding is found in other demyelinating disorders but is less common in tumors or abscesses. Therefore, it seems to have some diagnostic value in multiple sclerosis.
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The carcinogenicity of beta-cyclodextrin, a cyclic, water-soluble carbohydrate comprising seven glucose units, was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the compound in their diet at concentrations of 0 (control), 2.5 or 5% for 104 wk. Surviving rats were then given a basal diet for a further 5 wk and killed at 109 wk. The dose levels were selected from the results of a 13-wk subchronic toxicity study. Dose-dependent inhibitory effects of beta-cyclodextrin on growth were observed in both sexes of the treated groups. The survival rates, mean survival times and range, however, demonstrated no significant differences between the control and treated groups. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rat, and no statistically significant increase in the incidence of any tumour was found for either sex of the treated groups. Thus, it is concluded that under the present experimental conditions, the high dose, about 340-400 times higher than the current daily human intake from ingestion as a food additive and from pharmaceutical use, does not have any carcinogenic potential in F344 rats.
BACKGROUND: Efficacy of flecainide acetate for the treatment of fetal supraventricular tachycardia with cardiac failure was reported. CASE: For a case in which maternal digoxin therapy failed, flecainide acetate (400 mg/day) is used from 27 weeks. Cardioversion with improved cardiac function occurred 6 days after treatment. Fetal serum flecainide acetate level was 292 ng/ml which was 64% of the maternal level (453 ng/ml). No adverse maternal side effects were noted with 11 weeks of therapy. A vigorous male baby, weighing 3,610 g, Apgar 8/9, Ua-pH 7.24, was born. He is now 1 year of age and in good condition with medication of 5 mg/kg flecainide acetate. CONCLUSION: Flecainide acetate seemed to be safe for both mother and fetus, and effective for the treatment of fetal supraventricular tachycardia which is refractory to transplacental digoxin therapy.
Interrelationships among induction of cytochrome P-450 (CYP) 1A1/2, decrease in connexin 32 (Cx32), and liver tumor-promoting activity by beta-naphthoflavone (BNF) in the promotion stage were examined in a 2-stage liver carcinogenesis model. A total of 20 male Fischer 344 rats were initiated with a single intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DEN) or were given the saline vehicle alone. Starting 2 weeks later, they were fed a diet containing 2%, 1%, or 0% BNF for 6 weeks. All animals were subjected to a two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. Absolute and relative liver weights were significantly increased in the DEN+BNF groups as compared to the DEN-alone group. Diffuse hepatocellular hypertrophy with cytoplasmic eosinophilia, sometimes accompanied by development of adenoma-like hepatic foci, was observed in the BNF-treated rats. Remarkable induction of cytochrome CYP 1A1/2 and significant increase in CYP 2E1 were noted in the DEN+BNF groups, and positive immunohistochemical staining for both was observed diffusely. The areas of Cx32-positive spots per hepatocyte in the centrilobular areas of livers of the BNF-treated rats were significantly decreased, but no changes were observed in periportal areas. The numbers and areas of foci positive for glutathione S-transferase placental form were increased in the BNF-treated groups. These results suggest that BNF is a liver tumor promoter that, unlike phenobarbital, does not induce CYP 2B1/2 isozymes, and there seems to be no direct relationship between CYP 1A1/2 induction and Cx32 reduction in BNF hepatocarcinogenesis.
A rare seminal vesicle adenocarcinoma was found in a 109-wk-old Fischer 344 (F344) rat. At necropsy, the right seminal vesicle was enlarged, containing a 15- x 18- x 18-mm mass. The neoplasm occupied almost the entire seminal vesicle lumen and consisted of epithelial cells arranged in papillary, glandular, and solid patterns. Tumor cells were larger than their normal counterparts in the seminal vesicles and had round nuclei and abundant cytoplasm. Clusters of macrophagelike cells with less abundant cytoplasm and indented nuclei were apparent in the lumina of the glandular structures formed by the tumor cells. No metastasis to other tissues or organs was observed. Immunohistochemically, tumor cells were positive for keratin and S-100, and the macrophagelike cells bound antibodies against vimentin and ED-1. Ultrastructurally, the tumor cells exhibited many small secretory granules, some microvilli, and intercellular junctions. The macrophagelike cells, in contrast, were characterized by lysosomes and abundant rough endoplasmic reticulum. Therefore, a diagnosis of seminal vesicle adenocarcinoma with intraluminal macrophage infiltration was made. This is the first case report of such a seminal vesicle tumor in an F344 rat.
In order to examine whether fenbendazole has tumor-promoting activity, a total of 70 male Fischer 344 rats were initiated with a single intraperitoneal injection of 100 mg/kg of diethylnitrosamine (DEN) or were given the saline vehicle alone; beginning 1 wk later, rats were given a diet containing 3,600; 1,800; 600; 200; 70; or 0 ppm of fenbendazole for 8 wk. Subgroups of 5 rats each from the DEN+ 1,800; DEN+0; 1,800; and 0 ppm groups were euthanatized after 1 wk of fenbendazole treatment, and the remaining animals were euthanatized at 8 wk. After 1 wk, relative liver weights (ratios to body weights) were significantly increased in the DEN+ 1,800 and 1,800 ppm groups, and based on light microscopy, periportal hepatocellular hypertrophy was evident in these groups. After 8 wk, relative liver weights were significantly increased in the groups given > or =600 ppm with or without DEN initiation. Periportal hepatocellular hypertrophy, characterized by a marked increase in smooth endoplasmic reticulum, was observed in the groups given > or =600 ppm with or without DEN initiation. Induction of cytochrome P-450 (CYP) 1A2, 2B1, or 4A1 was noted in the fenbendazole-treated groups with or without DEN initiation; that associated with CYP 1A2 was most marked. Positive immunostaining for anti-CYP 1A1/2 or CYP 2B1/2 was observed diffusely in the livers of animals in the DEN+1,800 and DEN+3,600 ppm groups. The numbers and areas of connexin 32 (Cx32)-positive spots per square centimeter in centrilobular hepatocytes were significantly decreased in an almost dose-dependent manner with fenbendazole treatment after DEN initiation. In situ hybridization for Cx32 mRNA revealed a remarkable decrease in its expression in the centrilobular hepatocytes in the DEN+70 ppm group. The numbers of glutathione S-transferase placental-form positive single cells (plus mini foci) were significantly increased in the DEN+ 1,800 and DEN+3,600 ppm groups. Since those agents that induce CYP 2B1/2 isozymes and reduce Cx32 in centrilobular hepatocytes have been suggested to be liver tumor promoters, the present results indicate that fenbendazole may be a liver tumor promoter.
Dumon Y-stents and Dynamic stents are used to treat carinal stenosis, but their placement severely impairs the expectoration of secretions, making frequent bronchoscopic aspiration necessary. We report here five patients with terminal lung cancer who had stenosis of the lower trachea and main bronchi treated using spiral Z-stents. A long tapered spiral Z-stent was placed in the lower trachea and one main bronchus, and a short straight spiral Z-stent in the contralateral main bronchus. No patients required bronchoscopic aspiration of secretions after stenting. Before stenting, all of the patients were severely dyspnoeic, requiring oxygen and having to sit in the orthopnoeic position. After stenting, the patients' dyspnoea improved, with one patient becoming ambulant without the need for oxygen support. These results suggest that the use of spiral Z-stents in stenosis of the tracheal carina in advanced lung cancer is effective in reducing the need for bronchoscopic aspiration and enhancing quality of life.