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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 433 records · Page 24Linked to original sources

Synthesis of oligodeoxyribonucleotide with aliphatic amino or phosphate group at the 5' end by the phosphotriester method on a polystyrene support.

Lipophilic protecting groups mTrNH(CH2)n X (mTr:monomethoxytrityl, X = NH,O,S, n = 2,3,4,6) were attached to the 5'-phosphoryl group of 3'-O-protected thymidine. When the diamine derivatives (X = NH2) were used, the time course of the stability of mTr groups on the amino group and the phosphoramidate linkage with 80% aq. AcOH was measured. It was found that the mTr group was removed from the amino group rapidly and that the phosphoramidate linkage was more stable. It's stability depended upon the length of the CH2 linker. Oligonucleotides with an aliphatic amino group at their 5'-ends were synthesized by the phosphotriester method on a polystyrene support using protected nucleotides with P-O or P-S linkages. In the case of product with a P-S linkage, 5'-O-phosphorylated nonadecanucleotide was also prepared by I2-H2O treatment.

Oligodeoxyribonucleotides↗

Different modifying response of butylated hydroxyanisole, butylated hydroxytoluene, and other antioxidants in N,N-dibutylnitrosamine esophagus and forestomach carcinogenesis of rats.

The modifying effects of antioxidants were examined in a carcinogenesis system after N,N-dibutylnitrosamine treatment. Male F344 rats were given 0.05% N,N-dibutylnitrosamine in their drinking water for 4 wk and then treated with basal diet containing 2% butylated hydroxyanisole (BHA), 1% butylated hydroxytoluene (BHT) with 7 ppm vitamin K, 0.8% ethoxyquin, 5% sodium L-ascorbate, 5% sodium erythorbate, or no added chemical for 32 wk. BHA enhanced forestomach carcinogenesis but did not enhance esophageal carcinogenesis. BHT enhanced esophageal carcinogenesis but did not enhance forestomach carcinogenesis. Ethoxyquin significantly enhanced esophageal tumorigenesis. Neither esophageal nor forestomach carcinogenesis was affected by the other antioxidants evaluated. BHA significantly increased DNA synthesis of the forestomach epithelium, whereas BHT tended to increase that of the esophageal epithelium. Thus, BHA and BHT showed different modifying responses in carcinogenesis of the esophagus and forestomach.

Animals↗

Metabolism of 2- and 3-tert-butyl-4-hydroxyanisole (2- and 3-BHA) in the rat (I): Excretion of BHA in urine, feces and expired air and distribution of BHA in the main organs.

The mechanism of the carcinogenic or toxic action of BHA on rat forestomach was examined by studies on the excretion and tissue distribution of radioactivity in F344 male rats given tert-butyl- or methoxy-labelled 3-BHA orally. Within 2 days after a single oral dose of labelled BHA at 1 g/kg body wt, 87-96% of the 14C was excreted, mainly in the urine with smaller amounts in the feces and expired air. More 14C was found in the tissues of rats given the methoxy-labelled compounds. The distributions of 14C in the forestomach and the glandular stomach were similar. At 168 h after treatment, more 14C was found in the forestomach of rats given 2-BHA than in that of rats given 3-BHA. These results indicate that excretion of BHA is rapid, that 4-O-methyl demethylation may take place readily and that demethylated methyl group may become distributed non-specifically in tissues. The carcinogenic or toxic action of BHA on the forestomach does not seem to be due accumulation of BHA in the forestomach.

Air↗

Stimulatory effect of short-chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for trophic effects of fermentable fibre, gut microbes and luminal trophic factors.

1. Effects of short-chain fatty acids (SCFA) on epithelial proliferation of the intestine were studied in ileally fistulated rats fed on an elemental diet. 2. The stimulatory effect of daily doses of acetic, propionic and n-butyric acids (100, 20 and 60 mM respectively; pH 6.1) per fistula (3 ml, twice daily) on crypt cell production rate (CCPR) appeared within 2 d and lasted for at least 5 d. 3. The daily doses of SCFA for 14 d increased daily CCPR three to four fold. This effect was independent of the presence of gut bacteria. 4. Effects of SCFA were dose-dependent and varied among acids (butyrate greater than propionate greater than acetate). The effect was independent of low lumen pH. 5. In contrast, SCFA inhibited epithelial proliferation of isolated rat caecal tissue in vitro. 6. These results suggest that SCFA are physiological lumen trophic factors mediated by a systemic mechanism in vivo. 7. It is concluded that SCFA are involved in the trophic effects of gut microbes, ingestion of fermentable fibre, and lumen contents.

Acetates↗

Reciprocal modifying effects of isomeric forms of aminophenol on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine.

The effects of four isomeric forms of aminophenols, ortho-, meta-, para-aminophenol and acetaminophen (o-, m-, p-AP and AAP, respectively) on liver and kidney carcinogenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested. Rats were given 0.1% EHEN (in their drinking water for 2 weeks) and then diet containing these compounds at concentrations of 0.8% for 49 weeks. Administration of o-AP and AAP significantly decreased the number and area of preneoplastic foci staining immunohistochemically for glutathione S-transferase placental type (GST-P) per unit area of liver section as compared with the values for rats given EHEN alone. o-AP and AAP also significantly decreased the incidence of hepatocellular carcinoma. In contrast, p-AP and AAP significantly increased quantitative values for kidney preneoplastic lesions and renal cell adenoma. It is suggested that the cytotoxic effects of these chemicals preferentially suppressed the proliferation of preneoplastic liver cells, but stimulated the mitotic activity of preneoplastic tubular lesions in the kidney.

Acetaminophen↗

Short-chain fatty acids and water in the hindgut contents and feces of rats after hindgut bypass surgery.

Omnivorous experimental animals with different levels of short-chain fatty acids in hindgut contents or in feces were established by surgical bypass of the colon and/or the cecum. Levels of short-chain fatty acids, amounts of luminal contents, and the water contents in these animals were compared. Regional variations in water absorption and retention of luminal contents are likely to be major factors in the regulation of hindgut functions.

Animals↗

[A case of alpha-fetoprotein, carcinoembryonic antigen and human chorionic gonadotropin producing renal cell carcinoma].

A 51-year-old woman was admitted with a complaint of a left hypochondralgia and an abdominal mass. Laboratory testing showed a markedly increased alpha-fetoprotein (AFP) level (234,700 ng/ml). The enlargement of the left kidney and the adrenal gland was noted by CT scan and a tumorous thrombus was shown by inferior caval venography. The patient underwent a left nephrectomy, a combined resection of the spleen, tail of the pancreas and the removal of a tumorous caval thrombus. The patients AFP level gradually decreased after surgery. In a histological study, the tumor was diagnosed as a renal cell carcinoma and the presence of AFP, CEA, and HCG in the cancer cells was demonstrate by means of the "PAP" method.

Biomarkers, Tumor↗

Role of the glucopyranose ring in the elicitation of feeding.

To relate the structural characteristics of the glucose pyranose ring to feeding elicitation, biochemically and structurally similar glucose analogues were investigated to determine if they could elicit short- or long-term effects on food intake in rats. Testing solutions were infused once into unrestrained and unanesthetised rats through a chronically indwelling cannula in the third ventricle. D-Glucose markedly decreased meal size in doses from 6 to 24 mumol, but it's epimers, D-mannose, D-allose and D-galactose, did not affect food intake. Among the glucose analogues modified at C-2, rats treated with 12 mumol D-glucosamine ate a much larger size of meal than those with 12 mumol halogenglucoses or 24 mumol 2-deoxy-D-glucose, while 2-fluoro-2-deoxy-D-glucose with 2-chloro-2-deoxy-D-glucose induced a more potent feeding than 2-deoxyglucose. Glucosamine also induced hyperglycaemia, but did not affect plasma insulin. Activity of glucose, sensitive neurons in the lateral hypothalamus was increased by electro-osmotic application of 2-deoxyglucose or glucosamine, and the reciprocity was observed on neurons of the ventromedial hypothalamus. One-aminoglucose (beta-D-glucopyranosylamine), which is an aminoglucose analogue modified on C-1, increased meal size and more potently prolonged the duration of the meal compared to 1-deoxyglucose (1,5-anhydroglucitol). Together with the behavioural and structural characteristics of glucose analogues, a hydroxyl group on C-1 or C-2 is involved in feeding elicitation. The magnitude of the effect can be partly explained by the chemical concept of 'inductive effect'.

Animals↗