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Biomedical subjects

K Toyoda

Publications and source records attributed to K Toyoda.

At least 217 records · Page 12Linked to original sources

Effects of four antioxidants on N-methyl-N'-nitro-N-nitrosoguanidine initiated gastric tumor development in rats.

The effects of antioxidant administration during the post initiation phase of gastric tumor development were investigated in male Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Animals (20/group) were given MNNG in the drinking water (100 mg/l) for 8 weeks, and for the duration of this treatment were also fed on diet supplemented with 10% sodium chloride. Thereafter, they were divided into 6 groups and were maintained on diet containing either 2% butylated hydroxyanisole (BHA), 1% BHA, 1% butylated hydroxytoluene (BHT), 1% ethoxyquin (EQ) or 1% DL-alpha-tocopherol (alpha-TP) for 32 weeks. A carcinogen control group was fed the basal diet without antioxidant supplementation. The experiment was terminated 40 weeks after the beginning of administration of MNNG and development of gastroduodenal tumors was determined histopathologically. EQ significantly increased the incidence of tumors in the glandular stomach. No modification of tumor development in this region of the organ were observed with 2% BHA, 1% BHA, 1% BHT or 1% alpha-TP, although both 2% BHA and 1% BHA induced and/or promoted tumor development in the forestomach. In addition, nephrocalcinosis was identified only in the kidneys of rats given EQ after MNNG treatment.

Animals↗

Pneumotoxicity of butylated hydroxytoluene applied dermally to CD-1 mice.

Pneumotoxicity of butylated hydroxytoluene (BHT) applied to the skin of CD-1 mice was investigated and compared with that of butylated hydroxyanisole (BHA). To 6 groups of 10 male mice and 10 female mice 0.1 ml of dimethylsulfoxide (DMSO) solutions containing 0, 5, 10, 20, or 30 mg of BHT or 30 mg of BHA were topically applied 3 times weekly for 4 weeks. Between the 4th and 8th day BHT-treated mice exhibited respiratory distress with subsequent dose-dependent mortality. At autopsy dead animals were found to have congestion and enlargement of the lung with oozing of froth from the trachea. Histologically, collapse of the alveoli and dilatation of the alveolar ducts associated with degeneration or necrosis of type I alveolar epithelial cells were evident. The lethal effect of BHT was more manifest in female than in male mice. In contrast, none of the BHA-treated or control mice showed lung abnormalities. In another series of experiments to study the species difference of BHT pneumotoxicity, F-344 rats of both sexes and male Syrian golden hamsters were exposed to BHT by dermal application 3 times weekly for 4 weeks at a dose of 240 mg in rats or 480 mg in hamsters. However, no pulmonary alterations were observed in either species.

Animals↗

Scanning electron microscopic study of precancerous and cancerous pancreatic lesions induced by N-nitrosobis (2-oxopropyl) amine in Syrian golden hamsters.

Sequential alteration of Syrian golden hamster pancreatic ducts and ductules was investigated by scanning electron microscope during and subsequent to 10 weekly subcutaneous injections of N-nitrosobis (2-oxopropyl) amine (BOP). By examining surface morphology of ductal cells and resin casts of the secretory branches arising from the common duct, a series of lesions ranging from slight derangement of the luminal dimensions and loss of cilia to marked projections of "finger-like" processes accompanied by pleomorphism at the cellular and microvilli levels and increase in numbers of goblet cells could be established. A ductal histogenesis is proposed on the basis of the present scanning electron microscopic and earlier light microscopic findings.

Animals↗

Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

Ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide were tested for tumor-promoting activity in a two-stage stomach carcinogenesis experiment. Male outbred Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/liter) and a diet supplemented with 10% sodium chloride for 8 weeks. Thereafter, they were maintained on drinking water containing either 10% ethanol, 1% potassium metabisulfite, 0.5% formalin (formaldehyde) or 1% hydrogen peroxide for 32 weeks and then sacrificed for necropsy and histological examination. In the pylorus of the glandular stomach, potassium metabisulfite and formaldehyde significantly increased the incidence of adenocarcinoma after initiation with MNNG and sodium chloride. Hydrogen peroxide did not enhance the tumor yield, and ethanol showed a tendency to decrease neoplastic development. In the forestomach the incidence of squamous cell papilloma was significantly increased in the groups given hydrogen peroxide or formaldehyde, irrespective of prior initiation. Duodenal adenocarcinoma was induced by the initiation alone (10%) and the incidence was not affected by the subsequent treatments. The results indicate that potassium metabisulfite and formaldehyde both exert tumor-promoting activity in the rat glandular stomach.

Adenocarcinoma↗

Inhibitory effect of dibutyltin dichloride on pancreatic adenocarcinoma development by N-nitrosobis(2-oxopropyl)amine in the Syrian hamster.

The effects of a single intragastric application of dibutyltin dichloride (DT), at a dose of 30 mg/kg body weight, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis were studied in female Syrian golden hamsters. DT, which has been shown to selectively induce bile duct injury, was administered either 1 week before or after BOP initiation. BOP was injected subcutaneously once a week for 5 weeks at a dose of 10 mg/kg body weight. Controls were injected with BOP alone or given DT without carcinogen. Animals sacrificed at the end of the 25-week experimental period showed a significant inhibitory effect of DT on pancreatic carcinoma induction when DT was given before BOP treatment, although no such influence was evident with DT treatment following BOP exposure. These results indicate that the bile duct and more especially common bile-duct injury induced by DT may be relevant to the inhibition of the initiation stage of BOP-induced pancreatic carcinoma development in Syrian hamsters.

Adenocarcinoma↗

Lack of carcinogenicity of 8-nitroquinoline on long-term in vivo test in hamsters.

Syrian golden hamsters were administered 8-nitroquinoline, at a concentration of 0.05%, in a 10% ethanol solution as drinking water for 104 weeks. The animals were kept under observation until 112 weeks of age when the experiment was terminated. Both control and treated groups developed tumors in a pattern indistinguishable from that usually observed in Syrian golden hamsters. Thus the result of this experiment indicates that 8-nitroquinoline given orally at a concentration of 0.05% is not carcinogenic in Syrian golden hamsters.

Administration, Oral↗

[Comparison between FT-207 and 5-FU on intravesical absorption--experimental study on intravesical absorption in the dog].

FT-207 and 5-FU (1,200 mg) were administered intravesically to 5 mongrel dogs, and their concentration in the serum and bladder wall was measured. The serum concentration was high in both groups because their molecular weights are less than 200. The serum concentration of FT-207 was approximately 40 times higher than that of 5-FU. This difference may be due to the fact that non-ionized molecules in FT-207 account for more than 80% but those in 5-FU account for less than 10%.

Absorption↗

[Treatment with combination of antibiotics and human gamma-globulin (SM-4300) for severe infection in surgery].

The beneficial effects of gamma-globulin, which were used for agammaglobulinemia and severe infectious disease as an adjuvant or combination therapy in conjunction with antibiotics, are well known. In this study, a new intravenous human gamma-globulin (SM-4300) was administered to 5 patients with bacterial infection and 2 patients with viral infection. In 4 out of 7 patients (57.1%), several symptoms such as high fever, general fatigue and pain were improved clinically. Furthermore, there were no side effects due to SM-4300 either in clinical findings or in laboratory examinations.

Aged↗

Preparation and clinical utility of antihuman lymphocyte microsome gamma-globulin.

To eliminate side effects inherent to the administration of the presently available antilymphocyte serum (ALS), microsomal fractions of lymphocytes have used as the antigen. Antiserum produced using microsomal fraction from mouse thymus cell as the antigen proved to have potent immunosuppressive activity. Subsequently, microsomal fraction from cultured human lymphocytes was used to produce potent immunosuppressive antisera. The antisera thus prepared was found to have a high leucoagglutinin titer. The antihuman lymphocyte microsome gamma-globulin (AHLMG) prepared was administered to 6 patients undergoing renal transplantation from living donors. Severe rejection episodes and serious side effects such as anaphylactoid reaction and thrombocytopenia were nil. This AHLMG which is devoid of side effects yet retains immunosuppressive activity warrants extended purification.

Adolescent↗

Management of massive hemobilia with angiographic embolization.

Two cases of angiographic embolization for the management of massive hemobilia due to hepatico-jejunostomy and percutaneous transhepatic biliary drainage are presented. The clinical features are described together with a short review of the literature. In addition to defining the bleeding source, angiography provides an effective and safe alternative to surgery for the control of hemobilia.

Aged↗

Artificial structure of chromatin derived in the preparation process.

Nuclei were isolated from mouse lymphoma L5178Y cells in the exponential growth phase, and chromatin was prepared by mechanical treatment of the nuclei. The nuclei and the chromatin were then digested to various extents with micrococcal nuclease and the resulting mono- and dinucleosome fractions of the two preparations were compared. During progressive digestion mononucleosomes from chromatin retained H1 histone and a DNA length of 165 base pairs, whereas those from nuclei released H1 histone and the length of their DNA decreased to 140 base pairs at an early stage of digestion. These nucleosomal preparations were always associated with nonhistone proteins. The dinucleosomes from nuclei contained larger amounts of nonhistone proteins than those from chromatin, but half of these proteins was released during the process of cleavage into mononucleosomes. The final mononucleosome preparation from nuclei retained 20% less nonhistone proteins than that from chromatin. The contents of nonhistone proteins in mono- and dinucleosomes from chromatin were the same. The electrophoretical distributions of molecular species of nonhistone proteins in mononucleosomes from nuclei and chromatin were different from each other: during digestion the profile of the former changed, whereas that of the latter remained constant. It is tentatively concluded that both H1 histone and nonhistone proteins were bound to nucleosomes more or less loosely in intact nuclei in situ, but that when the nuclear structure was disrupted these proteins became more tightly bound.

Animals↗