Search PubMed⌕ Search

Biomedical subjects

Y Yano

Publications and source records attributed to Y Yano.

At least 109 records · Page 6Linked to original sources
PubMed1998

Stimulatory effects of lipoprotein(a) and low-density lipoprotein on human umbilical vein endothelial cell migration and proliferation are partially mediated by fibroblast growth factor-2.

We previously reported a transient increase in plasma lipoprotein(a) (Lp(a)) concentrations following acute myocardial infarction and surgical operations, and demonstrated Lp(a) accumulation in healing tissues. In the present study, the stimulatory effect of Lp(a) on migration and proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by quantitative assay methods and compared it with that of LDL. Lp(a) stimulated both migration and proliferation of HUVEC in a dose-dependent manner and the stimulatory activities for migration and proliferation were two times higher than those of LDL in terms of moles of apoB. In addition, this stimulatory activity of Lp(a) was not affected by the difference of Lp(a) phenotype. Although each neutralizing antibody to hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and interleukin-1beta (IL-1beta) had no further effect on migration and proliferation of HUVEC treated with Lp(a), only antibody to fibroblast growth factor-2 (FGF-2) partially suppressed them. Moreover, pertussis toxin, which inhibits FGF-2-stimulated endothelial cell movement, also partially suppressed Lp(a)-induced HUVEC migration. FGF-2 concentrations in the medium of HUVEC treated with Lp(a) were constant in spite of the increase in FGF-2 mRNA levels in HUVEC. Taken together, it is suggest that Lp(a) stimulates HUVEC migration and proliferation, which is mediated, at least in part, by FGF-2 and may promote the angiogenesis during wound healing.

Antibodies↗
PubMed1998

The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in mice based on the regulation of polyamine metabolism.

The present study was carried out in order to estimate a usefulness of vitamin E against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Feeding high doses of vitamin E suppressed the NNK-induced elevation of the activity of ornithine decarboxylase, a key enzyme of polyamine biosynthesis, in the lungs of mice at 4 weeks after injection. In contrast, the vitamin elevated the NNK-induced decrease of the activity of spermidine/spermine N1-acetyltransferase, a key enzyme of polyamine biodegradation. In conjugation with these events, the NNK-increased level of proliferating nuclear cell antigen as a marker of cell proliferation was suppressed by vitamin E treatment. Also, the supply of high doses of vitamin E suppressed NNK-induced lung tumorigenesis in mice. These results suggest that vitamin E inhibits the development of lung tumors in mice treated with NNK, partly due to the regulation of polyamine metabolism.

Animals↗
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

[A case of emergency surgery for acute mitral regurgitation due to complete papillary muscle rupture as complication of acute inferior myocardial infarction].

We experienced a case with acute mitral regurgitation caused by complete posterior papillary muscle rupture as complication of acute inferior myocardial infarction, who underwent successfully emergency operation of mital valve replacement and coronary revascularization in acute stage. A 64-year-old woman developed sudden cardiogenic shock shortly after the onset of acute inferior myocardial infarction. The diagnosis of acute inferior myocardial infarction was based on the electrocardiographic findings. Under IABP support, preoperative coronary angiography visualized total occlusion of segment 3 of the right coronary artery, and preoperative left ventriculography showed akinesis of inferior wall and severe mitral regurgitation. At 6 hours after onset of papillary muscle rupture, emergency operation was performed. At operation, posterior papillary muscle was found to be totally ruptured. Coronary artery revascularization and mitral valve replacement were performed. Postoperative course was uneventful, with 4 days of IABP and 5 days of ventilatory support. She was discharged on the twentieth postoperative day in NYHA class I. Reports of successful emergency operation for total papillary muscle rupture following acute myocardial infarction are rare. Early diagnosis and surgical treatment are mandatory to save this group of patients.

Emergencies↗
PubMed1998

Calcitonin gene-related peptide affords gastric mucosal protection by activating potassium channel in Wistar rat.

BACKGROUND & AIMS: Calcitonin gene-related peptide (CGRP) protects the gastric mucosa against injurious stimuli in various experimental models. The underlying mechanism could be the increase in gastric mucosal blood flow (GMBF). A number of endogenous vasodilators exert their effects through the activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels on vascular smooth muscle. The present experiments were performed to elucidate whether CGRP increases GMBF through the activation of KATP channels and whether the channels are involved in the protection by CGRP of gastric mucosa. METHODS: GMBF was determined by the hydrogen-clearance technique in male Wistar rats. Mucosal lesions were produced by intragastric superfusion with 0.15N HCland 15% ethanol for 40 minutes. Effects of an agonist (Y-26763, intra-arterially) and an inhibitor (glibenclamide, intravenously) of KATP channels were tested. RESULTS: Y-26763 increased GMBF, which was abolished by glibenclamide, and a CGRP-induced increase in GMBF was attenuated by glibenclamide. Macroscopic and microscopic lesions were exacerbated by human CGRP-(8-37) (a CGRP-1 receptor antagonist; intra-arterially) and glibenclamide but were ameliorated by exogenous CGRP (intra-arterially). CONCLUSIONS: CGRP protects the gastric mucosa against ulcerogenic stimuli, at least in part, through the activation of KATP channels in rats.

Animals↗
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

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

Application of logistic growth model to pharmacodynamic analysis of in vitro bactericidal kinetics.

A new pharmacodynamic model for the analysis of in vitro bactericidal kinetics was developed based on the logistic growth model, with the bacterial phases divided into two compartments. The model equations are expressed as nonlinear simultaneous differential equations, and the Runge-Kutta-Gill method was adopted to numerically solve the equations in both the simulation and the least squares curve-fitting procedures. The model can describe the initial killing and the regrowth phases and can explain the nonlinear dependence of the killing rate on the drug concentration. The model can also explain the plateau in the bacterial growth curve that is often observed in in vitro experiments. The model was applied to analysis of the in vitro time-killing data of beta-lactam antibiotics, S-4661, meropenem, imipenem, cefpirome, and ceftazidim against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The results of curve-fitting using the least squares program MULTI (Runge) showed good fits for all types of drugs and bacteria. The relationship between the characteristics of the drug-bacteria interactions and the estimated pharmacodynamic parameters is discussed.

Anti-Bacterial Agents↗
PubMed1998

Circulating levels of 7 S domain of type IV collagen and atrial natriuretic peptide in normotensive type 2 diabetic patients with or without retinopathy.

Thickening of the basement membrane and other structural alterations of the vascular walls occur frequently in patients with diabetes. The vascular response to atrial natriuretic peptide (ANP) is also altered in these patients. Abnormal vascular response in diabetes may be due to alteration of vascular physicochemical properties induced by accumulation of components of vascular basement membrane. The aim of this study was to evaluate the relationship between circulating levels of the 7 S domain of type IV collagen (7 S-collagen), and ANP in normotensive type 2 diabetic patients with or without retinopathy. Forty-one normotensive type 2 diabetic patients (n = 19 with and n = 22 without retinopathy) and 18 age-matched control subjects participated in the study. Serum 7 S-collagen and plasma ANP levels were measured by radioimmunoassays. Serum 7 S-collagen (4.4 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01) levels and plasma ANP (20.8 +/- 1.0 vs 15.5 +/- 1.0 pg/ml; p < 0.01) were significantly higher in diabetic patients than in normal subjects. Serum 7 S-collagen increased significantly in diabetic patients without retinopathy compared with normal subjects (4.1 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01). Diabetic patients with retinopathy showed significantly higher circulating concentrations of 7 S-collagen (4.6 +/- 0.1 vs 4.1 +/- 0.1 ng/ml; p < 0.01) and ANP (22.9 +/- 1.4 vs 18.9 +/- 1.3 pg/ml; p < 0.05) than those without retinopathy. There was a significant and positive correlation (r = 0.51, p < 0.01) between the circulating levels of 7 S-collagen and ANP in all patients. The results of this investigation showed that increased circulating levels of ANP correlate with the abnormal metabolism of the vascular basement membrane observed in diabetic patients with microangiopathy.

Atrial Natriuretic Factor↗
PubMed1998

A crossover study of oral administration of UFT in chronic liver disease: comparison of continuous and intermittent schedules.

This study was aimed at evaluating the tolerance to an intermittently administered oral UFT for hepatocellular carcinoma (HCC) with chronic liver disease (CLD). Ten patients who had received curative therapy for HCC with CLD (Child's classification A or B) were randomly assigned either an intermittent schedule (IS), oral administration of UFT (130 mg/m2/b.i.d.) with 2 days rest a week, or a continuous schedule (CS), consecutive administration of UFT with the same dose. On day 12, the serum concentration of 5-fluorouracil (5-FU) was measured. After 2 weeks rest, the patients were switched to the other schedule for 10 weeks and the concentration of 5-FU was measured on day 12. The median values of the area under the curve (AUC) and maximum concentration (Cmax) of 5-FU in IS and CS were 187.7 and 263.2 ng/ml/h, 57.1 and 93.0 ng/ml, respectively. Both the AUC and Cmax for IS were significantly lower than those for CS. One IS patient had tolerable diarrhea, while three of the CS patients had intolerable nausea and one had hemorrhagic gastritis. IS seemed to be a suitable measure for CLD.

Administration, Oral↗
PubMed1998

Population pharmacokinetics of vancomycin in Japanese adult patients.

Population pharmacokinetic parameters of vancomycin (VCM) in Japanese adult patients infected with methicillin-resistant Staphylococcus aureus (MRSA) were estimated using 1253 items of serum concentration data from 190 patients obtained in routine drug monitoring. The two-compartment linear model was adopted, and VCM clearance (CL) was correlated with the creatinine clearance (CLcr), which was observed or estimated by the Cockcroft-Gault equation. The population pharmacokinetic analysis program NONMEM with first-order conditional estimation method was used. The results showed VCM clearance to be linearly correlated with CLcr (CL [ml/min] = 0.797 x CLcr) when the estimated CLcr was <85 ml/min, but no linear relationship at higher than this level because of the lack of accuracy in the CLcr estimates. The interindividual variability of CL was 38.5%; K12 and K21 were 0.525 hr(-1) and 0.213 hr(-1), respectively. The distribution volume at steady state (V[SS]) was 60.71, with no significant dependence on the actual body weight. The interindividual variability of Vss was 25.4%. The calculated half-life (t1/2,beta) in a typical patient with CLcr of 85 ml/minute was 12.8 hours. Residual variability was 23.7%. These results were compared to those of healthy volunteers, and guidelines for dosage adjustment in VCM therapy are discussed.

Adult↗
PubMed1998

Population pharmacokinetics of vancomycin in Japanese pediatric patients.

The population pharmacokinetic profile of vancomycin (VCM) in Japanese pediatric patients infected with methicillin-resistant Staphylococcus aureus was analyzed using 181 samples of serum concentration data from 49 patients obtained in routine drug monitoring. The one-compartment linear model was adopted, where the VCM clearance (CL) and the distribution volume (Vd) were correlated with covariates such as postnatal age (AGE) and body weight (BWT). The population pharmacokinetic analysis program NONMEM with the first-order conditional estimation method was used. The results showed that the population mean clearance normalized by BWT increases with AGE up to 1 year of age [CL(L/hour per kg) = 0.1 19 + 0.0619 x (AGE - 1)] and decreases with age over 1 year old [CL(L/hour per kg) = 0.119 + 0.00508 x (1 - AGE)]. The population mean of the distribution volume normalized by BWT was independent of AGE (Vd (L/kg) = 0.522). The interindividual variability of CL was 39.6%, and that of Vd was 18.8%. The intraindividual, residual variability was 34.6%. These results were compared with those in other articles, and a guideline for dosage adjustment in VCM therapy is discussed.

Adolescent↗
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

Adaptive changes in membrane lipids of barophilic bacteria in response to changes in growth pressure.

The lipid compositions of barophilic bacterial strains which contained docosahexaenoic acid (DHA [22:6n-3]) were examined, and the adaptive changes of these compositions were analyzed in response to growth pressure. In the facultatively barophilic strain 16C1, phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) were major components which had the same fatty acid chains. However, in PE, monounsaturated fatty acids such as hexadecenoic acid were major components, and DHA accounted for only 3.7% of the total fatty acids, while in PG, DHA accounted for 29.6% of the total fatty acids. In response to an increase in growth pressure in strain 16C1, the amounts of saturated fatty acids in PE were reduced, and these decreases were mainly balanced by an increase in unsaturated fatty acids, including DHA. In PG, the decrease in saturated fatty acids was mainly balanced by an increase in DHA. Similar adaptive changes in fatty acid composition were observed in response to growth pressure in obligately barophilic strain 2D2. Furthermore, these adaptive changes in response were also observed in response to low temperature in strain 16C1. These results confirm that the general shift from saturated to unsaturated fatty acids including DHA is one of the adaptive changes in response to increases in pressure and suggest that DHA may play a role in maintaining the proper fluidity of membrane lipids under high pressure.

Journal Article↗
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↗