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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 505 records · Page 28Linked to original sources

Alterations in neutral amino acid transport across the blood-brain barrier in hepatic failure.

The accelerated transport of the blood neutral amino acids into the brain in encephalopathic patients with fulminant hepatitis and advanced liver cirrhosis was demonstrated not only by determining the cerebrospinal fluid (CSF) aminogram but also by calculating the predicted velocity of the amino acid transport through the blood-brain barrier. Significant elevation in CSF aromatic amino acid (AAA) and methionine levels was observed in the encephalopathic patients. Arousal from hepatic encephalopathy by drip infusion of a branched chain amino acid (BCAA)-enriched solution was obtained coincidentally with the elevated BCAA levels and diminished concentrations of AAA and methionine in CSF. These clinical observations were confirmed experimentally in rats treated with carbon tetrachloride (CCl4) and D-galactosamine by obtaining the elevation of neutral amino acid contents in the brain and the slight increase in the brain uptake index (BUI) of a radiolabeled amino acid.

Amino Acids↗

Brain tyrosine hydroxylase activity and calculated amount of brain dopa synthesized in carbon tetrachloride-intoxicated rats.

Tyrosine hydroxylase activity in the corpus striatum was measured in a large dose of carbon tetrachloride (CC14)-intoxicated rats in order to confirm whether brain catecholamine contents decrease in acute hepatic failure or not. Theoretical amounts of dopa synthesized in the brain of the treated animals were calculated according to an equation of enzyme kinetics. Tyrosine hydroxylase activities in CCl4-injured rats were similar to those in control rats, and calculated amounts of brain dopa in liver-injured rats were rather higher as compared to those in untreated animals.

Amino Acids↗

Feeding suppression induced by intra-ventricle III infusion of 1,5-anhydroglucitol.

1,5-Anhydroglucitol (1-DG) has been known as an antimetabolic glucose analogue. Using gas chromatography, 1-DG was found to be physiologically present in rat serum. In order to investigate its direct and long-term effects on feeding, 1-DG was infused during the light period into the rat third ventricle in doses of 3.0, 6.0 and 12.0 mumol/rat. Its effects were then compared to those of similarly applied 2-deoxy-D-glucose (2-DG). Following initial hyperphagia, both of these glucose-analogues produced suppressive effects on feeding during the subsequent day throughout the light and dark periods. On the third day after 2-DG injection reduction of feeding did not recover completely to the pretreatment baseline levels, but it did recover after 1-DG. Both 1-DG and 2-DG caused linear dose-related hypophagia, with the slope for 1-DG being about half of that for 2-DG. It is suggested that the delayed hypophagia which followed the initial hyperphagia produced by deoxyglucose was a result of sustained inactivation of the Na-pump due to intracellular ATP deficiency caused by accumulation of deoxy-glucose-6-phosphate.

Animals↗

Stimulatory effect of short chain fatty acids on the epithelial cell proliferation in rat large intestine.

1. Short chain fatty acids [SCFA: acetate 75, propionate 35, butyrate 20 (microM)] introduced intraluminally into the colon increased the mitotic index and the labeling index of the large intestinal epithelial cells within 60 min in fasted rats. 2. Epithelia that lacked direct contact with SCFA were also stimulated. 3. SCFA did not have such a stimulatory effect either in vagotomized rats or in sympathectomized rats. 4. These results suggest that SCFA stimulate epithelial cell proliferation in the large intestine of fasted rats via the autonomic nervous system.

Animals↗

Effect of quercetin on two-stage carcinogenesis of the rat urinary bladder.

The initiating and promoting effects of quercetin on urinary bladder carcinogenesis in male F344 rats were examined histopathologically. No tumor or hyperplasia were observed in rats given 5.0% quercetin as initiator in the diet for 4 weeks followed by 0.001% N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) for 29 weeks. Moreover, administration of 5.0% quercetin diet for 25 weeks after initiation with 0.01% BHBN for 4 weeks did not promote urinary bladder carcinogenesis. Furthermore, no lesions were detected in rats given 5.0% quercetin diet only. These results suggest that quercetin is not carcinogenic to rat urinary bladder.

Animals↗

Sequential observations on the appearance of neoplastic lesions in the liver and kidney after treatment with N-ethyl-N-hydroxyethylnitrosamine followed by partial hepatectomy and unilateral nephrectomy.

Sequential observations were carried out on the induction of preneoplastic lesions in the liver and the kidney. Rats were initially given N-ethyl-N-hydroxyethylnitrosamine (EHEN) in their drinking water (0.1%) for 3 days (Group 1), 1 week (Group 2) or 2 weeks (Group 3) or tap water (Group 4). Rats in Groups 1-3 were subjected to partial hepatectomy and unilateral nephrectomy (right side) 2 weeks after the end of EHEN treatment. Rats from these groups were killed in week 10, 20, 30 and 40 of the experiment. In the liver, the effect of EHEN in the induction of gamma-glutamyltranspeptidase (gamma-GT) positive foci and hyperplastic nodules (HN) was clearly dependent on the length of treatment. The preneoplastic lesions increased with the lapse of observation time. Changes measured as number of gamma-GT positive foci were 10-40 times greater than those measured as HN, especially among the small size range. Values for changes in Group 1 given 0.1% EHEN for 3 days were very low, indicating that this dose is close to the threshold. Two rats with hepatocellular carcinoma in Group 3 given EHEN for 2 weeks survived until week 40. In the kidney, tubular epithelial proliferations composed of cells with slightly basophilic cytoplasm and slightly atypical nuclei were tentatively named atypical cell foci (ACF). EHEN induced ACF, renal cell adenomas and renal cell carcinomas. The increase in the induction of ACF was dependent on the length of observation period but not on the length of treatment. Even though control rats (not treated with EHEN) also had ACF, their quantitative values were far less than the groups given EHEN and killed at week 40, indicating that a large number of ACF were induced by EHEN. Therefore, EHEN is good for experimental induction of preneoplastic lesions in the liver and kidney of rats. The experimental schedule for Groups 1 and 2 could be used as a shortterm screening test for promoters and the schedule for Group 3 as an assay for inhibitors.

Animals↗

Effect of azathioprine and carbon tetrachloride on induction of hyperplastic liver nodule and hepatocellular carcinoma by diethylnitrosamine and N-2-fluorenylacetamide in rats.

The enhancing or inhibitory action of the hepatotoxic agents, carbon tetrachloride (CCl4) and azathioprine (AZP), on the evolution of hyperplastic liver nodule (HN) and hepatocellular carcinoma (HCC) in diethylnitrosamine (DEN)- and N-2-fluorenylacetamide (FAA)-treated rats (control group) was tested. The area of gamma-glutamyl transpeptidase(gamma-GTP)-positive HN and/or foci in the eighth week was remarkably small in rats fed on a diet containing FAA and AZP (the AZP group), but was quite large in rats fed a diet containing FAA in addition to repeated CCl4 injections (the CCl4 group). HCC was first detected in the 21st week and the incidence of HCC within the 36 weeks of the experiment was very high in the CCl4 group. However, no tumor, including HCC, was detected in the AZP group during this observation period. No essential differences in the biochemical characteristics of HCC between the control group and the CCl4 group were observed with respect to several enzyme activities. The increased activity of liver aniline hydroxylase observed 12 hr after the administration of FAA, AZP, or DEN decreased when AZP was administered simultaneously with FAA to rats treated with DEN in advance. The mechanisms of the enhancing of inhibitory effect observed are discussed with special reference to the drug-drug interactions.

2-Acetylaminofluorene↗

Mechanism of relaxant action of papaverine. III. Comparison of sodium ion dependencies on the relaxant effects of papaverine, Aspaminol and benactyzine in guinea-pig taenia coli.

The role of sodium ion on the relaxant action of papaverine in guinea-pig taenia coli contracted by hypertonic 40 mM KCl were studied by manipulating the external sodium ion concentration and compared with those of its allied antispasmodics, Aspaminol and benactyzine. Whereas all of the three antispasmodics relaxed the taenia in all media used herein, their relaxant activities were declined by eliminating sodium ion from the bathing media. The declined relaxant activities were restored by re-introducing sodium ion to the solution depending on the amount of sodium ion but sodium ion dependencies of the restoration were not equal for each. In a solution containing 20 mM sodium ion, almost complete restoration was encountered with papaverine, while displayed only a slight restoration with Aspaminol and benactyzine. When a small amount of sodium ion was applied to the taenia before or after the treatment with the antispasmodics, the relaxation in response to papaverine was augmented, but those in response to Aspaminol and benactyzine were not affected. All of the three antispasmodics inhibited the cellular 45Ca-uptake in all media. While, their inhibitory activities were reduced by eliminating sodium ion from the media and were not restored so markedly by re-introducing 20 mM sodium ion to the solution. From these findings, it is suggested that papaverine may induce the smooth muscle relaxation not only by inhibiting the Ca-influx independently of the presence of sodium ion but also by other mechanisms sensitive to sodium ion, by contrast, Aspaminol and benactyzine may evoke the relaxation through mechanisms less sensitive to the presence of sodium ion, which include the inhibition of Ca-influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of continued drinking on prognosis of alcoholic liver cirrhosis.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.

Adult↗

A simple and rapid method for determining blood ammonia levels.

Blood ammonia levels in patients with various liver diseases were determined quantitatively by a simple and rapid method using the Amitest Meter System. The results were compared to those obtained by an enzymatic method and were well correlated. This simple Amitest is also useful in animal experiments, particularly when there is a need to determine blood ammonia levels serially. This paper test was evaluated as being accurate and reliable for clinical and experimental use.

Ammonia↗

[T gamma lymphocytes in rheumatoid synovial membrane].

The proportion of T lymphocytes with receptors for the Fc portion of IgG (T gamma cells), revealed by mixed rosette assay, was determined in the synovial membrane and peripheral blood of 11 patients with rheumatoid arthritis. The percentage of T gamma cells in the lymphocytic infiltration of rheumatoid synovium was significantly lower than that found in peripheral blood (p less than 0.005). There was no significant difference between the percentage of T lymphocytes in the synovial tissue and that in peripheral blood. Depressed supressor activity of T lymphocytes in rheumatoid synovial membrane might lead B-lymphocytes to blastic transformation to the plasma cell series with consequent production of large amounts of immunoglobulins in the joint.

Adult↗

Inhibitory effect of butylated hydroxyanisole and ethoxyquin on the induction of neoplastic lesions in rat liver after an initial treatment with N-ethyl-N-hydroxyethylnitrosamine.

The effect of butylated hydroxyanisole (BHA) and ethoxyquin (EQ) on hepatocarcinogenesis initiated with N-ethyl-N-hydroxyethylnitrosamine in rats was investigated. The results clearly demonstrated that BHA and EQ inhibited the development of gamma-glutamyltranspeptidase - positive foci, hyperplastic nodules and hepatocellular carcinomas in the rat system employed.

Animals↗