Biomedical subjects

S Otani

Publications and source records attributed to S Otani.

At least 91 records · Page 5Linked to original sources

PubMed1998

Involvement of protein tyrosine phosphorylation in the effect of green tea polyphenols on Ehrlich ascites tumor cells in vitro.

Green tea extract and its polyphenolic components have been found to possess anticarcinogenic, antimutagenic, antihypertensive and antihepatotoxic effects, and several mechanisms have been proposed for these effects. In this study, the effects of five tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-) epicatechin-3-gallate (ECG), ( -) epicatechin (EC) and (+)-catechin (C), were examined on the viability of Ehrlich ascites tumor cells in vitro and a possible relationship with tyrosine phosphorylation was determined. Proteins extracted from the cells treated with the tea polyphenols were separated by SDS-PAGE, and tyrosine-phosphorylated proteins were detected by immunoblotting with anti-phosphotyrosine antibody and the extent of phosphorylation determined. EGC (100 microM) caused a significant decrease in cell viability to 4.1 +/- 0.2% of the control value, and this correlated with a stimulation of protein tyrosine kinase (PTK) activity. EGCG (100 microM) also caused a slight decrease in cell viability (approximately 70% of the control value) but this and the other polyphenols, which had no effect on cell viability likewise, had no effect on tyrosine phosphorylation. Tyrosine phosphorylations of 42 and 45 kDa proteins were also observed for EGC. Further evaluation of the effect of EGC showed that the activity of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis in cells, decreased significantly as well. A significant correlation has therefore been observed between a cellular event, namely, a reduction in the viability of Ehrlich ascites tumor cells and an association with a tyrosine phosphorylation of 42 and 45 kDa proteins by the polyphenol EGC.

Animals↗

PubMed1998

Epithelial cell proliferation in the digestive tract induced by space restriction and water-immersion stress.

The effects of space restriction and water-immersion stress on epithelial cell proliferation in the digestive tract, with special attention to the esophagus, stomach and duodenum, in 8-week-old SD male rats were examined. Histological assessment revealed spotted hemorrhagic lesions in the fundus of the glandular stomach, accompanied by statistically increased 5-bromo-2'-deoxyuridine (BrdU) labeling index in the fundic and pyloric regions. Furthermore, biochemical analysis demonstrated an increased activity of ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT), known as key late-limiting enzymes of the polyamine pathway, in the gastric fundus. The stress may induce a remarkable increase in expression of c-fos, c-jun and c-myc mRNAs in both fundic and pyloric regions of the glandular stomach. There were no remarkable changes in the esophagus. These results indicate that space restriction and water-immersion stress induced cell proliferation in the glandular stomach through overexpression of proto-oncogenes and increased ODC and SAT activities that might be related to the promotion of gastric carcinogenesis.

Acetyltransferases↗

PubMed1998

Restricted Zn2+ availability affects the antizyme-dependent ornithine decarboxylase degradation pathway in isolated primary cultured rat hepatocytes.

We previously reported that lack of Zn2+ decreased ornithine decarboxylase (ODC) activity without any change in ODC messenger RNA levels and the half-life of ODC activity being about 2-fold more rapid in primary cultured adult rat hepatocytes, suggesting that lack of Zn2+ decreased ODC activity mainly by degrading the enzyme. The present investigations showed that the chelator, diethylenetriamine penta-acetic acid (DTPA), increased the ratio of ODC-antizyme complex to total ODC (about 2-fold) and caused a decrease in antizyme inhibitor, a protein inhibitor of ODC antizyme (about 50%). These results indicate that a restricted Zn2+ availability affects the antizyme-dependent ODC degradation pathway and consequently decreases ODC activity in primary cultured rat hepatocytes.

Animals↗

PubMed1998

Characteristics of patients with hepatitis C virus with and without GB virus C/hepatitis G virus co-infection and efficacy of interferon alfa.

GB virus C/hepatitis G virus (GBV-C/HGV) infection seems to be common among patients with hepatitis C virus (HCV) infection. We studied retrospectively the proportions of patients with GBV-C/HGV RNA and antibodies to the GBV-C/HGV second envelope protein (anti-E2) among 149 subjects with chronic hepatitis C who had received interferon alfa. The clinical characteristics of patients with GBV-C/HGV RNA or anti-E2 were examined, as was the efficacy of the treatment. Stored serum specimens were tested for GBV-C/HGV RNA by the reverse transcription polymerase chain reaction and for anti-E2 by an enzyme-linked immunosorbent assay. Of the 149 patients before therapy, 8 (5%) had GBV-C/HGV RNA only, 72 (48%) had anti-E2 only, and 4 (3%) had both. The mean age of patients with GBV-C/HGV RNA (some with anti-E2) was significantly less than that of patients with anti-E2 only. Results of laboratory and histological evaluations were not different depending on the presence of GBV-C/HGV RNA or anti-E2. The GBV-C/HGV RNA titer decreased during therapy in all 12 patients with GBV-C/HGV RNA; only 4, with a low titer before therapy and with anti-E2 detected at some time, had sustained clearance of GBV-C/HGV. Our results suggested that half of the patients with chronic hepatitis C had been exposed to GBV-C/HGV, but in almost all, the virus had been cleared; also, even chronic GBV-C/HGV infection did not affect the severity of the disease arising from HCV. Interferon alfa treatment was sometimes effective against GBV-C/HGV, and anti-E2 may be associated with clearance of GBV-C/HGV.

Adult↗

PubMed1998

Vascular leiomyosarcoma arising from the inferior vena cava diagnosed by intraluminal biopsy.

A 61-year-old woman developed pain in the right thigh, paraplagia of the lower extremities and lumbago in November 1996. A lumbar spine roentgenogram showed lytic change in L2, and magnetic resonance imaging showed a patchy destructive lesion and compression of the dural sac from the right by a tumour. Computed tomography (CT) myelography showed a motheaten destructive lesion in L2 and projection of the tumour into the spinal canal. Abdominal ultrasound, CT and cavography showed dilatation of the inferior vena cava (IVC) and an intraluminal tumour about 2x2.8x4 cm in size in the IVC. The tumour arose from the IVC just beneath the renal vein and extended to just short of the right atrium. Both vertebral and intraluminal biopsy materials showed the same morphology, in which atypical spindle cells admixed with multinucleated giant cells proliferated in a fascicular growth pattern. Neoplastic cells were strongly positive for alpha-smooth muscle actin. We diagnosed vascular leiomyosarcoma arising from the IVC with metastasis to the lumbar vertebrae. Cases of vascular leiomyosarcoma diagnosed by intraluminal biopsy are rare.

Biopsy↗

PubMed1998

The repetitive activation of extracellular signal-regulated kinase is required for renal regeneration in rat.

In this study, we investigated the activation of p42 extracellular signal-regulated kinase (ERK2) during renal regeneration after HgCl2-induced acute renal failure (ARF) in rat. ERK2 activation was observed at 5 and 29 hr after HgCl2 injection, respectively. The tyrosine phosphorylation of hepatocyte growth factor receptor (c-MET) occurred between 2.5 and 5 hr after the treatment. On the other hand, the phosphorylation of epidermal growth factor receptor (EGFR) was transiently observed at 29 hr after the injection. The peak of ornithine decarboxylase activity as a marker of G1 phase was at 10 hr, and subsequently the labeling index of proliferating cell nuclear antigen as a marker of S phase increased at 53 hr. These results indicate that the repetitive activation of ERK2 related to the phosphorylation of c-MET and EGFR is required for the renal regeneration in HgCl2-induced ARF of rat.

Acute Kidney Injury↗

PubMed1998

Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex.

Using sharp-electrode intracellular recordings, we studied the dopaminergic facilitation of synaptic plasticity in layer I-II afferents--layer V neuron glutamatergic synapses in rat prefrontal cortex in vitro. Tetanic stimulation (100 pulses at 50 Hz, four times at 0.1 Hz) to layer I-II afferents induced N-methyl-D-aspartate receptor-independent long-term depression (>40 min) of the glutamatergic synapses when the stimulation was coupled with a bath-application of dopamine. Tetanic stimulation alone did not induce lasting synaptic changes. Dopamine application alone transiently depressed synaptic responses, which fully recovered within 30 min. Pharmacological analyses with antagonists suggested that dopamine action on either D1-like or D2-like receptors can facilitate the induction of long-term depression. However, results with agonists were not fully consistent with the antagonist results: while a D2 agonist mimicked the facilitatory dopamine effect, D1 agonists failed to mimic the effect. We also analysed the synaptic responses during tetanus and found that dopamine prolongs membrane depolarization during high-frequency inputs. Postsynaptic membrane depolarization is indeed critical for long-term depression induction in the presence of dopamine, since postsynaptic hyperpolarization during tetanus blocked the dopaminergic facilitation of long-term depression induction. Postsynaptic injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetra-acetic acid (100 mM in the electrode) also blocked long-term depression induction. Our results show that dopamine lowers the threshold for long-term depression induction in rat prefrontal glutamatergic transmission. A possible underlying mechanism of this dopaminergic facilitation is the enhancement of postsynaptic depolarization during tetanus by dopamine, which may increase the amount of Ca2+ entry from voltage-gated channels to the level sufficient for plasticity induction.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1998

Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells.

Impaired bone formation resulting from a decline of osteoblast activity has been implicated in the pathogenesis of diabetic osteopenia. We examined the effects of high glucose concentration alone, independent of insulin deficiency, on the growth of a human osteoblast-like cell line (MG-63). Sustained exposure to high glucose for 7 days inhibited cell growth in a concentration-dependent manner up to 49.5 mmol/L, as compared with cells cultured with a normal glucose concentration (5.5 mmol/L) or a high mannitol concentration (an iso-osmolar control). Glucose (49.5 mmol/L) attenuated the increment either in DNA content or in [3H]thymidine incorporation induced by insulin-like growth factor I (IGF-I). The IGF-I-induced increase of ornithine decarboxylase (ODC) activity, which plays an important role in cell growth, was also attenuated. The half-life of ODC protein was not shortened by the high glucose culture, but the intracellular content of putrescine (an end product of ODC) was significantly decreased. These changes did not occur in the high mannitol culture, strongly suggesting a specific effect of glucose. In summary, our observations suggest that a high glucose concentration significantly impairs the proliferative response of osteoblastic cells to IGF-I and that the defective cell function caused by sustained exposure to high glucose levels might contribute to impaired bone formation in patients with diabetic osteopenia.

Acetyltransferases↗

PubMed1998

Effect of preinduction of heat-shock proteins on acetic acid-induced small intestinal lesions in rats.

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that stress is known to cause the release of endogenous substances such as catecholamine, beta-endorphine, 5-hydroxytryptamine, corticotropin-releasing factor, and thyrotropin-releasing hormone (TRH). However, the role played by these neurohormonal mediators in bowel dysfunction under stress conditions is not well known. We investigated the influence of water-immersion stress or TRH administration on the expression of 60-kDa, 72-kDa, and 90-kDa heat-shock proteins (HSP60, HSP72, and HSP90, respectively) in rat small intestinal mucosa by Western blot and immunohistochemical analyses. The cytoprotective function of preinduced HSPs on experimentally induced mucosal damage also was studied. In order to investigate the influence of preinduction of HSP60 on small intestinal damage, the small intestinal lumen was perfused with 1.5% acetic acid 1 ml/min for 15 min with or without pretreatment with water-immersion stress or TRH administration. Expression of HSP60 was significantly increased by water-immersion stress or TRH administration in the small intestinal mucosa, whereas HSP72 and HSP90 did not increase. Interestingly, expression of this protein showed the biphasic peak pattern after water-immersion stress or TRH administration. Each peak was observed 3-6 hr and 21-24 hr after the initiation of water-immersion stress or TRH administration. Immunohistochemical study also showed a significant increment of HSP60 in both the cytoplasm and nuclei of the small intestinal mucosal cells. No histopathologic alteration was observed in rat small intestinal mucosa after each treatment. Small intestinal damage caused by 1.5% acetic acid perfusion was not influenced by preinduction of HSP60. We demonstrated that water-immersion stress or TRH administration specifically induced HSP60, although preinduction of this protein did not show a cytoprotective function in the small intestinal mucosa.

Acetic Acid↗

PubMed1998

Effects of follicle-stimulating hormone on endothelin receptors in cultured rat ovarian granulosa cells.

Two subtypes of the endothelin (ET) receptor (ETA and ETB) were studied in cultured ovarian granulosa cells. Immature 21-day-old female Wistar-Imamichi rats were implanted with diethylstilbestrol (DES) pellets for 5 days and granulosa cells were collected by repeated puncturing. Viable cells (2.5 or 5 x 10(5)) were cultured with 50--400 ng/ml of ovine NIH follicle-stimulating hormone (FSH) in the presence or absence of [125I-Tyr13]ET-1 (50 pM) in 1 ml McCoy's 5a medium for 72 h. FSH gradually increased the [125I-Tyr13]ET-1 binding to granulosa cells, whereas FSH-untreated granulosa cells had no significant changes. The dose of 200 ng/ml of FSH was most effective for [125I-Tyr13]ET-1 binding for 48-h culture, thereafter revealing a plateau. After 48 h of culture with 200 ng/ml of FSH, granulosa cells were further incubated with [125I-Tyr13]ET-1 (10 pM-1 nM) and/or [125I]IRL1620, the selective ETB receptor agonist (10 pM-1 nM) for 2 h for equilibrium study, and then the dissociation constant and the maximal binding capacity between receptors and ligands were determined by saturation curve and Scatchard plot analysis. ETA + ETB, ETB, and ETA (sites/cells) showed a 4.4-, 2.6-, and 7.5-fold increase, respectively. As for steroidogenesis, ET-1 (100 nM) or ET-3 (100 nM) suppressed FSH-induced progesterone and 17 beta-estradiol production. These results indicate that FSH upregulates both ETA and ETB receptors in DES-treated immature rat granulosa cells, with no significant differences between ET-1 and ET-3, and that ET-1 or ET-3 suppresses FSH-induced steroidogenesis. ETs may affect the granulosa cell function through the ETA and ETB receptors, and the increase in amount of ET binding does not reflect ET effects on granulosa cell function. The ET receptor plays an important role in the development of the ovary.

Animals↗

PubMed1998

Changes with age and sex in levels of plasma and ovarian or testicular endothelin-1 in rats.

Mammalian ovaries and testes contain various intragonadal peptides necessary to control gonadal function. Effects of aging and sex on total plasma and ovarian or testicular endothelin-1 (ET-1) levels were studied in female and male rats aged 4-140 days. At 2 weeks, plasma ET-1 levels were 2.69 +/- 0.09 and 2.41 +/- 0.03 pg/ml (mean +/- SEM; n = 10) in the female and male, respectively. After a temporary decrease, mean ET-1 concentrations increased at 10 weeks and again decreased at 20 weeks in the female, thereafter revealing a plateau, whereas the ET-1 concentrations gradually decreased in the male. In adult females, plasma ET-1 levels were 3.7-fold higher than male levels. Ovarian ET-1 levels gradually increased after birth to 2 weeks, then decreased, and again increased at 3 weeks. Thereafter they gradually decreased, showing a plateau after 10 weeks. In contrast, testicular ET-1 levels gradually decreased after birth. This difference is parallel to but much larger than the sex difference in ovarian or testicular ET-1. Gonadal ET-1 showed a very different ontogeny.

Adsorption↗

PubMed1998

Relationship between glutathione and polyamine metabolism after partial hepatectomy in alcohol-treated rats.

In a liver regeneration inhibiting model after partial hepatectomy in rats, we determined hepatic glutathione concentration and studied its relation with polyamine, an indicator of liver regeneration. Experiment 1: Male ODS rats and Wistar rats as control were maintained with vitamin C-deficient diets for 2 weeks. In the alcohol group, 3 g/kg of ethanol was administered orally 1 hr before partial hepatectomy. Experiment 2: Wistar rats were divided into four groups, according to the presence or absence of alcohol and vitamin E (VE), and a 6-week pair-feeding was done. As for partial hepatectomy, about 70% of the total liver was excised. As a result, in experiment 1, hepatic glutathione levels were significantly decreased by acute alcohol administration in both ODS and Wistar rats, and its level of alcohol administration group of ODS rats was the lowest. Hepatic ornithine decarboxylase activity and putrescine level 4 hr after partial hepatectomy showed almost a similar behavior, being the lowest in the alcohol administration group of ODS rats. In experiment 2, hepatic glutathione level showed no influence by chronic alcohol administration, but was the lowest in the VE-deficient alcohol administration group. Hepatic ODC activity and putrescine level 4 hr after partial hepatectomy showed no influence by chronic alcohol administration, but was the lowest in the VE-deficient alcohol administration group. These results clarified that intrahepatic glutathione levels before partial hepatectomy were decreased in the models in which hepatic ODC activities after surgery were suppressed.

Animals↗

PubMed1998

Expression and localization of ornithine decarboxylase in reversible papillomatosis induced by uracil in rat bladder.

Direct mechanical irritation by uracil calculi formed following feeding of 3% uracil in the diet to male rats produces severe papillary hyperplasia (papillomatosis, which is reversible) of bladder epithelium. To evaluate the mechanism of the appearance of uracil-induced papillomatosis, we examined the changes of the enzyme activity and the localization of ornithine decarboxylase (ODC), as well as polyamine biosynthesis, and epithelial proliferation, that accompany the sequential bladder epithelial changes following administration and withdrawal of uracil. Moreover, expression of ODC mRNA was investigated using northern blotting and localization of ODC mRNA was demonstrated using in situ hybridization. ODC activity during uracil administration was maintained at a high level compared to that in normal epithelium, but sharply decreased after cessation of uracil treatment. The accumulation of ODC protein was observed in the proliferating bladder epithelium by immunohistochemical examination and western blotting analysis, and even after cessation of treatment, the protein binding to anti-ODC antibody remained mildly elevated. Sequential changes of proliferating cell nuclear antigen (PCNA)-positive cells in the epithelium during the development and disappearance of papillomatosis correlated with ODC activity. ODC mRNA was expressed strongly in the proliferating epithelium in rats treated with uracil and weakly in normal epithelium, in accordance with the location of ODC protein. Consequently, our data demonstrate that cell proliferation in the development of papillomatosis is closely associated with polyamine metabolism, and moreover suggest that ODC activity is up-regulated at a post-translational step.

Animals↗

PubMed1998

Polyamine metabolism of rat gastric mucosa after oral administration of hypertonic sodium chloride solution.

Oral administration of 1 ml of 3.42 M NaCl solution to rats induced spermidine/spermine N1-acetyltransferase (SSAT) activity in gastric mucosa as well as ornithine decarboxylase (ODC) activity. SSAT activity increased and peaked at 5 h and again at 7 h, whereas ODC activity peaked at 6 h. SSAT mRNA also increased after 3.42 M NaCl administration to an extent similar to the increase in SSAT activity at 5 h. Intracellular putrescine level and DNA synthesis were increased by NaCl administration. A polyamine oxidase inhibitor, N,N'-bis(2,3-butadienyl)-1,4-butanediamine (MDL-72527), but not an ODC inhibitor, alpha-difluoromethylornithine (DFMO), inhibited the increases in putrescine level and DNA synthesis at 5 h. The inhibition of DNA synthesis by MDL-72527 was reversed by putrescine administration. In contrast, both MDL-72527 and DFMO inhibited the increase in putrescine level and DNA synthesis at 16.5 h. These findings suggest that putrescine produced from preexistent spermidine by SSAT is responsible for the initial DNA synthesis after mucosal injury induced by NaCl and that both SSAT and ODC are involved in formation of putrescine, which is required for subsequent DNA synthesis.

Acetyltransferases↗

PubMed1998

Leptin affects pancreatic endocrine functions through the sympathetic nervous system.

The effects of leptin on the secretion of insulin and glucagon were examined. In an experiment involving insulin response to an i.v. glucose load in vagotomized rats, the plasma concentrations of insulin were significantly lower in the leptin (20 nmol/kg BW)-treated group than in a control group. However, in intact rats and rats that had undergone both vagotomy and chemical sympathectomy, this suppressive effect of leptin on insulin secretion was not detected. In an experiment involving a hypoglycemia-induced glucagon secretion test in intact rats, an i.v. injection of leptin (20 nmol/kg BW) augmented the plasma glucagon response to hypoglycemia. In the case of sympathectomized rats, however, this stimulative effect of leptin on glucagon secretion was not detected. In an experiment with perfused rat pancreas, the addition of leptin (20 nM) to the perfusate slightly suppressed insulin secretion, but had no effect on basal or glucopenia-induced glucagon secretion. In intact rats infused with leptin (0.31 micromol/day), the expression of uncoupling protein-1 messenger RNA in interscapular brown adipose tissue was increased, whereas no such effect of leptin on the uncoupling protein-1 messenger RNA expression was observed in brown adipose tissue in chemically sympathectomized rats. These findings suggest that leptin might indirectly affect pancreatic endocrine functions, probably through its stimulative effects on the sympathetic nervous system.

Adipose Tissue, Brown↗

PubMed1998

Effect of alcohol abuse on polyamine metabolism in hepatocellular carcinoma and noncancerous hepatic tissue.

BACKGROUND: Alcohol abuse is a risk factor for hepatocellular carcinoma (HCC) and the recurrence of HCC after resection. We therefore investigated polyamine metabolism, which is important in cell proliferation, HCC tissue, and noncancerous hepatic tissue. METHODS: In 30 patients who underwent liver resection for HCC, 13 patients had drunk 86 gm or more ethanol per day for at least 10 years (group 1), whereas the remaining 17 patients were nondrinkers or occasional drinkers (group 2). The control subjects were five patients who did not have liver disease or abuse alcohol. Tissue ornithine decarboxylase (ODC) activity and polyamine concentrations were measured. RESULTS: ODC activity in the HCC tissue was significantly higher in group 1 than in group 2. ODC activity in noncancerous tissue was significantly higher in group 1 than in group 2 and the control group. The ratio of spermidine/spermine in the HCC tissue was significantly higher in group 1 than in group 2. The ratio in noncancerous tissue was significantly higher in groups 1 and 2 than in the control group. CONCLUSIONS: Alcohol abuse affects polyamine metabolism, which influences the grade of malignancy of HCC. Hepatic tissue has greater potential for carcinogenesis in patients with chronic liver disease and alcohol abuse than in patients without them.

Aged↗

PubMed1998

[Perioperative management of two patients with severe dilated cardiomyopathy].

We report perioperative management of two patients with severe dilated cardiomyopathy belonging to the group IV of classification of Inoh (ejection fraction 18% and 30%). In the preoperative period, they developed severe congestive heart failure. Dopamine, dobutamine, and furosemide were given to improve cardiac function. Anesthesia was performed safely under continuous cardiac output and mixed venous saturation monitoring. We consider that preoperative evaluation and management are very important to prevent intraoperative and postoperative complications in patients with severe dilated cardiomyopathy.

Aged↗

PubMed1998

[Recurrent nerve palsy after endotracheal intubation].

We encountered left recurrent nerve palsy in four patients who had undergone surgery unrelated to the course of the vagus nerve or recurrent nerve, during which they had received endotracheal anesthesia. They were intubated without difficulty and underwent surgery without trouble, but postoperatively they all complained of hoarseness. We used a disposable ENTRASOFT endotracheal tube with high volume, low-pressure cuff in three patients and a disposable PORTEX endotracheal tube with low volume, standard cuff in one patient. In three patients recurrent nerve palsy healed completely within two months after the operation, and one patient was recovering from the palsy on the twentieth day after the operation. We believe that the most plausible explanation of recurrent nerve palsy is the excessive pressure from the inflated endotracheal tube cuff on the intralaryngeal course of the anterior branch of the recurrent nerve. Monitoring cuff pressure is most important to prevent recurrent nerve palsy after endotracheal intubation.

Adult↗