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Biomedical subjects

S Otani

Publications and source records attributed to S Otani.

At least 181 records · Page 10Linked to original sources
PubMed1994

Effect of sucrose monostearate, an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells.

Sucrose esters of fatty acids have antitumor activity. We studied the effect of sucrose monostearate (SS), an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells. The activity of ornithine decarboxylase (ODC) was increased in the cells by changing the medium. This increase in the activity was inhibited by adding sucrose stearate, but not sucrose or stearate to the medium. The activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of polyamine biodegradation, was enhanced with the addition of SS in a time- and dose-dependent manner. The elevation of SAT activity was completely prevented when cycloheximide was added to the culture simultaneously. In in vitro studies, SS at various concentrations up to 1 mM hardly affected the activities of ODC or SAT. The incorporation of [3H]inositol into both fractions of inositolphospholipid and inositol phosphates was inhibited by SS. These results suggest that the perturbation of polyamine metabolism and phosphatidylinositol turnover is involved in the mechanism of antitumor activity of SS in Ehrlich ascites tumor cells.

Acetyltransferases↗
PubMed1994

Vitamin E acts as a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice.

The present study was designed to evaluate whether vitamin E could be a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice. Starting at 6 weeks of age, groups were divided into three groups, i.e. A/J mice fed a control diet (A/J control), A/J mice fed a vitamin E-supplemented diet (A/J vitamin E) and ddY mice fed a control diet (ddY control). At the 28th experimental week, nuclear NADPH-driven active oxygen generation, thiobarbituric acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in A/J mice fed a control diet were significantly higher than those in the ddY control group. A/J mice fed Vitamin E for 28 weeks could decrease the levels of TBARS and DNA-SSB with a significant difference, as compared with those in A/J control mice. The nuclear alpha-tocopherol levels in A/J controls were significantly lower than those in ddY controls, on the contrary, the vitamin feeding to A/J mice increased nuclear alpha-tocopherol levels more than that in the ddY controls. At the 40th experimental week, lung tumor incidence and tumor multiplicity (percentage of mice with tumors) in A/J controls were reduced and brought close to those in ddY control mice by vitamin E. Then the alpha-tocopherol level in plasma of A/J controls was significantly lower than the level in plasma of ddY controls, and the level in tumor-bearing mice in A/J controls also showed a lower level with significant difference as compared to that in non-tumor-bearing mice of A/J controls. These results suggest that the difference in susceptibility to spontaneous lung tumorigenesis between A/J and ddY mice partly depends on the difference of oxidative stress on the pulmonary nuclei, and vitamin E can act as a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice.

Animals↗
PubMed1994

Suppressive effects of the extracts of Japanese edible seaweeds on mutagen-induced umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002) and tumor promotor-dependent ornithine decarboxylase induction in BALB/c 3T3 fibroblast cells.

Some of epidemiological data indicated that ubiquitous consumption of seaweeds in Japan may be a possible protective factor against some types of tumor. To analyse this problem, the authors studied the antimutagenic and antitumor promotion activities in methanol-soluble extracts of typical edible seaweeds which showed suppressive effects on 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indol (Trp-P-1)-induced umu C gene expression in SOS response of Salmonella typhimurium (TA 1535/pSK 1002) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-dependent ornithine decarboxylase induction in BALB/c 3T3 fibroblast cells. Although eight varieties of edible seaweeds including chlorophyta, Phaenophyta and Rhodophyta showed significant antimutagenic and antipromotion activities, they expressed the activities different from each other. Among these seaweeds, Enteromorpha prolifera ('Sujiaonori' in Japanese) and Porphyra tenera ('Asakusanori') showed relatively strong suppressive activities in both antimutagenic and antipromotion assays compared with other seaweeds. These seaweeds contained considerable amounts of beta-carotene as a possible active principle with anticarcinogenic activity. This compound was partially associated with the antimutagenic activity in the seaweed extract, but did not contribute to the antipromotion activity of seaweed extract under our experimental conditions. These results strongly suggest that Japanese edible seaweeds have possible antimutagenic and antipromotion activities probably associated with antitumor activity.

3T3 Cells↗
PubMed1994

Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions.

Two organosulfur compounds, methyl propyl disulfide (MPD) and propylene sulfide (PS) from garlic and onions, were studied for their modifying effects on hepatocarcinogenesis in the F344 rats. Modifying potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form (GST-P)-positive foci in the liver. MPD and PS significantly reduced both these parameters of GST-P-positive foci in a dose-dependent manner. To investigate possible mechanisms of inhibition, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities were measured. In MPD and PS-high dose-treated liver tissue there was a tendency for their decrease, albeit non-significant, which suggested that the inhibitory effect might have been caused by decreased cell proliferation associated with decreased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus necessary to consider various effects in assessing possible protective roles of garlic and onions.

Allium↗
PubMed1994

Rapid development of somatic spines in stratum granulosum of the adult hippocampus in vitro.

Somatic spines on granule cells have been observed occasionally in the adult rat dentate gyrus in vivo. Here we evaluate the appearance and formation of somatic spines in s. granulosum from adult rat hippocampal slices immediately after slice preparation, 45 min, 3 h, and 5 h later. Initially somatic spines are extremely rare but, after 3 h in vitro, they are readily apparent. Some of these somatic spines form asymmetric synapses that have a spherical vesicle-containing presynaptic bouton and a postsynaptic density. Other somatic spines lack a postsynaptic density and may also lack an apposed presynaptic bouton (free somatic spines) as observed in single thin sections. Both the number of these free somatic spines and the number of somatic spine synapses increase in a time-dependent manner. No somatic spines were observed on CA1 pyramidal cells in the same hippocampal slices. Electrophysiological observations indicate that the formation of somatic spine synapses on granule cells in the hippocampal slice occurs without any apparent granule cell activation. The trigger event for this very rapid synaptogenesis in the adult dentate gyrus remains to be determined.

Animals↗
PubMed1994

Enhancement by organosulfur compounds from garlic and onions of diethylnitrosamine-induced glutathione S-transferase positive foci in the rat liver.

Ten organosulfur compounds from garlic and onions were studied for their modifying effects on diethylnitrosamine-induced neoplasia of liver in male F344 rats using the medium-term bioassay system of Ito based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control group given diethylnitrosamine alone. In experiments 1 and 2, high doses of diallyl sulfide, diallyl trisulfide, allyl methyl sulfide, allyl methyl trisulfide, and dipropyl sulfide had enhancing effects on focus formation. In contrast, high doses of methyl propyl disulfide and propylene sulfide significantly decreased the number of glutathione S-transferase placental form-positive foci. In the third experiment, combined treatment with the five chemicals that had enhancing activity were fed at low doses and increased the induction of glutathione S-transferase placental form-positive foci. To investigate the mechanism of the modifying effect on hepatocarcinogenesis, ornithine decarboxylase activity was measured in diallyl sulfide-, allyl methyl sulfide-, and dipropyl sulfide-treated liver tissue without prior initiation with diethylnitrosamine, and its activity was increased compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. Formation of 8-hydroxydeoxyguanosine, a DNA adduct generated by activated oxygen species, and lipid peroxidation (2-thiobarbituric acid-reacting substance production) were also not changed. These results suggest that the promoting effect could be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is appropriate to consider not only the possible protective role of garlic and onions but also their enhancing effects.

Allium↗
PubMed1994

The involvement of polyamines in the activation of vitamin D receptor from porcine intestinal mucosa.

In the intracellular process of the action of calcitriol, vitamin D receptor is thought to undergo some kind of physiochemical change, called activation, before the receptor binds to the vitamin D response element of the gene. In this paper, the effects of polyamines and their analogues on the sedimentation properties of vitamin D receptor prepared from porcine intestinal mucosa, and on DNA binding activity of the receptor, were studied. In sucrose density gradient analysis, polyamines decreased the sedimentation coefficient of vitamin D receptor in a dose-dependent fashion. Polyamines increased DNA binding activity of vitamin D receptor dose-dependently. These findings show that polyamines can activate vitamin D receptor in vitro. Among naturally existing polyamines, spermidine and spermine, but not putrescine, were effective within their physiological intracellular concentrations, suggesting that both spermidine and spermine can activate vitamin D receptor in vivo as well. Sucrose density gradient analysis using various kinds of polyamine analogues having various numbers of cations showed that the number of cation of polyamines is important for the efficiency to change the sedimentation coefficient of vitamin D receptor, and that the distance between two cationic charges does not play an important role.

Animals↗
PubMed1994

Regulation of 60-kDa heat shock protein expression by systemic stress and 5-hydroxytryptamine in rat colonic mucosa.

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that 5-hydroxytryptamine (5-HT) mediates alteration of bowel motility. In this study, the effects of water-immersion stress and the administration of 5-HT on the expression of a 60-kDa heat shock protein (HSP60) in rat colonic mucosa were investigated. The effect of YM-060, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, on the expression of this protein was also studied. Water-immersion stress and the administration of 5-HT induced synthesis of HSP60 in rat colonic mucosa. The induction of HSP60 and the number of defecations were clearly inhibited by the oral administration of YM-060. Our results suggest that the induction of HSP60 in rat colonic mucosa by water-immersion stress may be associated with gastrointestinal motility mediated by 5-HT, especially via 5-HT3 receptors.

Animals↗
PubMed1994

Increased spermidine or spermine level is essential for hepatocyte growth factor-induced DNA synthesis in cultured rat hepatocytes.

BACKGROUND/AIMS: Hepatocyte growth factor is a potent mitogen for mature hepatocytes and seems to act as a trigger for liver regeneration. Hepatocyte growth factor was first purified from human and rabbit plasma and rat platelets. Additionally, putrescine, spermidine, and spermine are widely distributed in many different cells; intracellular concentrations of these polyamines are closely related to cell proliferation. The present study examined whether polyamine metabolism is involved in hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes. METHODS: Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[1-14C]ornithine and S-adenosyl-L-[carboxyl-14C]methionine, respectively. RESULTS: alpha-Difluoromethylornithine inhibited hepatocyte growth factor-induced DNA synthesis by only 21%. On the other hand, methylglyoxal bis(guanylhydrazone) completely inhibited hepatocyte growth factor-induced DNA synthesis to nontreated control level. The inhibitory effect of methylglyoxal bis(guanylhydrazone) on hepatocyte growth factor-induced DNA synthesis was reversed by exogenously added spermidine or spermine. CONCLUSIONS: Spermidine or spermine is essential for hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes.

Adenosylmethionine Decarboxylase↗
PubMed1994

Induction of heat shock protein and prevention of caerulein-induced pancreatitis by water-immersion stress in rats.

Water-immersion stress is known to be involved in the development of hemorrhagic pancreatitis in caerulein-induced pancreatitis, when the stress is given following caerulein injection. The effects of pre-treatment with water-immersion to caerulein-induced pancreatitis were investigated in this study. 1. A 60-kDa heat shock protein was induced by pre-treatment with water-immersion stress in the pancreas. 2. Intra-peritoneal injection of caerulein (40 micrograms/kg) induced acute pancreatitis in rats without pre-treatment with water-immersion. However, when the rats were pre-treated with water-immersion, acute pancreatitis was not developed and no change of serum amylase levels was observed by i.p. injection of caerulein.

Amylases↗
PubMed1994

Enhancing effects of organosulfur compounds from garlic and onions on hepatocarcinogenesis in rats: association with increased cell proliferation and elevated ornithine decarboxylase activity.

Four organosulfur compounds from garlic and onions were examined for modifying effects on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats using the medium-term bioassay system based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas per cm2 of induced glutathione S-transferase placental form-positive foci. Isothiocyanic acid isobutyl ester (IAIE), dipropyl trisulfide (DPT), and allyl mercapton (AM) exerted enhancing effects on their development, while dimethyl trisulfide also tended to increase them. To investigate possible mechanisms of the modifying influence, sequential changes in ornithine decarboxylase activity (ODC) over 24 h were measured in AM-treated liver tissue without prior DEN initiation. The activity started to increase by 4 h after AM-treatment, and reached maximum at 16 h, compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. An increase in proliferating cell nuclear antigen-positive cells followed the elevation of ODC activity. These results suggest that IAIE, DPT, and AM promote rat hepatocarcinogenesis and their promoting effect might be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus appropriate to consider not only a possible protective role of garlic and onions, but also enhancing effects.

Acetyltransferases↗
PubMed1994

Relationship of ornithine decarboxylase activity and histological findings in human hepatocellular carcinoma.

To evaluate the correlation between the polyamine metabolism and the degree of malignancy in hepatocellular carcinoma, we measured ornithine decarboxylase activity and polyamine concentrations in neoplastic tissue and adjacent noncancerous tissue from resected specimens of liver from 30 patients. Ornithine decarboxylase activity, polyamines (putrescine, spermidine and spermine) and ornithine decarboxylase mRNA levels were significantly higher in hepatoma tissue than in noncancerous tissue. The activity of this enzyme in the tumor tissue had a negative correlation with the histological degree of differentiation judged according to a modification of the Edmondson and Steiner classification. Resected hepatoma tissue was stained immunohistochemically with antibodies for proliferating cell nuclear antigen (also called cyclin), a marker of cell proliferation. We noted correlation between ornithine decarboxylase activity and the number of cells stained for this antigen (r = 0.882, p < 0.001). These results indicate that ornithine decarboxylase activity is high in human hepatocellular carcinoma, leading to increased intracellular concentrations of polyamines. Ornithine decarboxylase activity also reflected the rate of tumor proliferation and was correlated with the histological findings.

Adult↗
PubMed1994

[Two-stage hepatectomy with preoperative portal vein embolization in rats].

We studied the functional reserve and ability to regenerate of non-embolized liver made hypertrophic by portal vein embolization (PVE) to evaluate the usefulness of two-stage hepatectomy with preoperative PVE. Rats underwent one of four treatments: 1, 70% hepatectomy; 2, 70% hepatectomy 7 days after PVE; 3, 30% hepatectomy; and 4, sham operation. Liver weight, the bromodeoxyuridine labeling index (LI), and the mitotic index (MI) were calculated after surgery. The lipid peroxide level of the liver, serum hepatic enzyme activities, total bilirubin concentration, prothrombin time, and antithrombin-3 activity were also assayed after surgery in each group. Non-embolized lobes made hypertrophic by PVE regenerated further after resection of the embolized portion of the liver. The increases in liver weight, LI, and MI in group 2 were significantly lower than in group 1, but tended to be higher than in group 3. In group 2, lipid peroxidation in the liver and postoperative disorders of liver function and the coagulation system were significantly less than in group 1, and were similar to those in group 3. Preoperative PVE increases not only the weight but also the function of the residual liver, which makes extended hepatectomy safer.

Animals↗