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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 757 records · Page 42Linked to original sources
PubMed1996

Effect of chronic ethanol feeding on Kupffer cell-mediated antitumor cell activity.

We have previously reported that the Kupffer cell has antitumor activity through mitochondrial damage to tumor cells by nitric oxide production. In this study, the effect of chronic ethanol feeding on antihepatoma cell activity of the Kupffer cell was examined in rats. Male rats of the Wistar strain were fed ethanol chronically for 8 weeks by liquid diets. Kupffer cells were isolated from the control rat or the ethanol-fed rat, and cocultured with AH 70 cells, a rat hepatoma cell line. Fluorescence of rhodamine 123 or propidium iodide was observed as indicators of the mitochondrial damage or cell membrane injury, respectively, by a laser scanning confocal microscopy. Mitochondrial damage of AH 70 cells as indicated by reduction of rhodamine 123 fluorescence was smaller by the coculture with Kupffer cell from the ethanol rat than that from the control. Cell membrane barrier dysfunction of AH 70 cell was less frequently observed with the Kupffer cell from ethanol-fed rats. A metabolite of nitric oxide (nitrite and nitrate) was less in the cultured medium with the ethanol Kupffer cell than with the control Kupffer cell. Ca2+ mobilization, which induces inducible nitric oxide synthase and observed by the fluorescence of fluo-3, in Kupffer cells cocultured with AH 70 cells was suppressed in ethanol-fed rats. These result suggests that chronic ethanol feeding suppresses antitumor cell activity of Kupffer cell through the impairment of Ca2+ mobilization and nitric oxide production.

Animals↗
PubMed1996

Effect of chronic ethanol feeding on nitric oxide synthesis by rat Kupffer cells.

Kupffer cells contribute to the important role of the liver defense mechanism through nitric oxide (NO) production. In this study, the effect of chronic ethanol administration on the ability of Kupffer cells to synthesize and release NO was investigated after stimulation with lipopolysaccharide (LPS). Male Wistar rats were chronically fed ethanol for 8 weeks according to the method described by DeCarli and Lieber et al. (J Nutr.91:331-336, 1967). Kupffer cells were isolated and cultured with LPS (1 micrograms/ml) for 24 hr. The levels of nitrite and nitrate, metabolites of NO, were determined in the culture medium, NO synthase (NOS) activity in Kupffer cells was determined by the method that measures conversion of [14C]arginine into [14C]citrulline. In control rats, a significant increase of nitrite and nitrate levels in culture medium was observed after LPS treatment. The magnitude of this increase was significantly smaller in chronic ethanol-fed rats. When the activity of NOS was determined, inducible NOS (iNOS) activity was higher than that of constitutive NOS, and LPS administration produced a significant elevation of iNOS activity in both control and chronic ethanol-fed rats. However, the elevation of iNOS activity by LPS stimulation was diminished by chronic ethanol administration. Distribution of iNOS in Kupffer cells as determined by an immunofluorescence method using a laser scanning confocal image system showed a lower expression of iNOS in chronic ethanol-fed rats even in the presence of LPS. These results demonstrate that the excessive production of NO by increased iNOS activity in Kupffer cells is diminished by chronic ethanol administration.

Animals↗
PubMed1996

Ethanol-induced oxidative stress in the liver.

Oxygen stress is well recognized to be a key step in the pathogenesis of ethanol-associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen-reactive species and/or by decreasing the level of endogenous antioxidants. Numerous experimental studies have emphasized the role of the ethanol-inducible cytochrome P-450 in the microsomes, as well as the molybdo-flavoenzymes xanthine oxidase in the cytosol. This review shows the putative role of ethanol-induced disturbances in iron metabolism in relation to iron as a prooxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Although many previous studies suggest a role for active oxygens in ethanol-induced mitochondrial dysfunction in hepatocytes, the detailed mechanism of ethanol-induced oxidative stress on mitochondria remains to be clarified further. Studies of our laboratory using a confocal laser scanning microscopic system strongly suggest that active oxidants produced during ethanol metabolism modulate mitochondrial energy synthesis in isolated and cultured hepatocytes. In addition, our investigations implicate endogenous glutathione-glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocyte mitochondria exposed to ethanol. The fluorographic investigations using the confocal laser scanning microscopy may be useful to extend our knowledge and provide a new view about ethanol-associated oxidative stress and metabolic changes in hepatocytes.

Animals↗
PubMed1996

Intron retention generates a novel isoform of the murine vitamin D receptor that acts in a dominant negative way on the vitamin D signaling pathway.

We identified and characterized a novel rat vitamin D receptor isoform (rVDR1), which retains intron 8 of the canonical VDR (rVDR0) during alternative splicing. In this isoform protein directed by the stop codon in this newly identified exon, a part of the ligand binding domain (86 amino acids) is truncated at the C-terminal end but contains 19 extra amino acids. The rVDR1 transcript was expressed at a level 1/15 to 1/20 of that of rVDR0 in the kidney and intestine in adult rats but not in embryos. The recombinant rVDR1 protein showed no ligand binding activity. Homo- and heterodimers of the recombinant rVDR0 and rVDR1 proteins bound to a consensus vitamin D response element (VDRE) but not to consensus response elements for thyroid hormone and retinoic acid. However, unlike rVDR0, rVDR1 did not form a heterodimeric complex with RXR on the VDRE. A transient expression assay showed that this isoform acted as a dominant negative receptor against rVDR0 transactivation. Interestingly, the dominant negative activities of rVDR1 differed among VDREs. Thus, the present study indicates that this new VDR isoform negatively modulates the vitamin D signaling pathway, through a particular set of target genes.

Alternative Splicing↗
PubMed1996

Identification of carriers of Duchenne/Becker muscular dystrophy by a novel method based on detection of junction fragments in the dystrophin gene.

We developed a Southern blotting based method that uses rare cutting restriction endonucleases and electrophoresis of single stranded DNA to detect junction fragments resulting from the rearranged dystrophin gene. By conventional Southern blot hybridisation, no junction fragments were detected in 27 unrelated patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy, who had 20 deletions and seven duplications in the dystrophin gene. With our new method, junction fragments were detected in 21 of these 27 patients. When the junction fragments were used as markers, five carriers were unequivocally diagnosed among six females from two families of DMD/ BMD patients. This novel method allows simple and definitive identification of carriers with risk factors for DMD/BMD without using quantitative Southern blot hybridisation.

Blotting, Southern↗
PubMed1996

Stapedial reflex in amyotrophic lateral sclerosis.

OBJECTIVE: To examine mechanisms controlling the stapedial reflex in patients with amyotrophic sclerosis (ALS). METHODS: The stapedial reflex was examined using impedance audiometry in 38 patients with sporadic ALS and in 25 age matched controls. RESULTS: All patients showed normal reflex decay test results. There were no significant differences between patients with ALS and control subjects in reflex threshold, latency, amplitude, or contraction time (C50). Although each reflex variable in the patients with classic or progressive muscular atrophy types of ALS showed no significant difference from that in control subjects, the patients with bulbar type ALS showed significantly longer latency, C50, and retraction time (D50), and significantly lower amplitude than control subjects. Three types of abnormal reflex waveforms (polyphasic, abnormally delayed retraction, and abnormally early retraction) were noted in six patients. CONCLUSION: The subclinical involvement of the stapedius motor neurons or of the supranuclear stapedius motor system might be responsible for the abnormalities of the stapedial reflex in ALS.

Acoustic Impedance Tests↗
PubMed1996

Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells.

It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

Animals↗
PubMed1996

Tumour necrosis factor receptor gene expression and shedding in human whole lung tissue and pulmonary epithelium.

This study aimed to investigate the expression of tumour necrosis factor receptor (TNF-R) at the gene and surface level, and its shedding in human lung tissue and a pulmonary epithelial cell line, A549. Levels of gene expression of TNF-R were evaluated by Northern blot analysis. Human lung tissue expressed both type I and type II TNF-R gene, while A549 cells expressed only type I TNF-R gene. Phorbol ester upregulated and TNF-alpha down-regulated the TNF-R gene expression in A549 cells. Consistent with these modulations of TNF-R gene expression, 125I-TNF binding capacities were increased with phorbol ester stimulation and decreased with TNF stimulation after 24 h in A549 cells. The shedding of TNF-R from A549 cells was investigated using enzyme-linked immunosorbent assay (ELISA) for soluble type I TNF-R. Not only lung tissues but also A549 cells spontaneously released soluble type I TNF-R into the culture medium. Both phorbol ester and TNF stimulation accelerated the shedding of soluble TNF-R from A549 cells. These results suggest that type I TNF-R gene expression and shedding of soluble TNF-R are differentially regulated in A549 cells. We conclude that tumour necrosis factor receptor surface expression is regulated, at least in part, at the gene expression level and shedding of soluble tumour necrosis factor receptor is modulated by inflammatory mediators, such as tumour necrosis factor in A549 cells.

Analysis of Variance↗
PubMed1996

Synthesis and biological activity of 4-amino-5-chloro-2-ethoxy-3-hydroxybenzamides, metabolites of a new gastroprokinetic agent, mosapride.

To confirm the proposed structures of the minor metabolites of a potential gastroprokinetic agent, mosapride, 4-amino-5-chloro-2-ethoxy-3-hydroxy-N-(2-morpholinylmethyl)benzamide (3) and the N-(5-oxo-2-morpholinyl)-methyl analogue 4 were prepared. As the common intermediate, 2-ethoxy-3-hydroxy-4-nitrobenzoic acid (15) was prepared via the regioselective ethylation of 2,3-dihydroxybenzaldehyde (10) and subsequent nitration of the resultant 2-ethoxy-3-hydroxybenzaldehyde (11). The key intermediate 15 was converted into the benzamides 3 and 4. After enzymatic treatment of the isolated metabolites, their structures were identified by comparison with the synthetic compounds. Serotonin-4 receptor binding affinity of these metabolites was found to be lower than that of mosapride.

Animals↗
PubMed1996

Steroid hormone-induced expression of the chicken ovalbumin gene and the levels of nuclear steroid hormone receptors in chick oviduct.

The induction of the chicken ovalbumin (OVA) gene by different classes of steroid hormones and the mRNA levels of estrogen (ER), progesterone (PR), and glucocorticoid (GR) receptors were studied in chick oviducts. Combined treatment with two hormones increased the induction of the OVA gene more than single treatment, when the levels of OVA mRNA were measured with Slot blot analysis. To discover the role of nuclear steroid hormone receptors as transcriptional factors in the OVA gene induction, we analyzed the levels of ER (with RT-PCR), PR, and GR mRNAs (with Northern blotting). The level of PR mRNA was increased only by estrogen, while no steroid hormone affected the levels of ER and GR mRNAs. Thus, these findings show that the levels of nuclear receptors do not reflect the OVA mRNA level in the oviduct of steroid hormone-treated chicks.

Animals↗
PubMed1996

Early diagnosis and estimation of pulmonary congestion and edema in patients with left-sided heart diseases from histogram of pulmonary CT number.

To establish an early diagnosis and have a quantitative estimation of congestion or edema, pulmonary CT scans were performed to detect the increase of regional lung water volume of patients with congestive heart failure. CT scanning of the upper, middle, and lower lung fields at maximum inspiration and hemodynamic analysis to ensure a hemodynamically chronic stable condition after the heart failure therapy for 5 weeks by cardiac catheterization within 2 weeks before CT scanning were performed in 10 normal subjects and 25 patients with left-sided heart failure. Patients were divided into two groups according to the presence or absence of pulmonary congestion or edema on chest radiographs, and the mean pulmonary wedge pressure (mPWP). The pulmonary congestion group (14 patients) had pulmonary congestion or edema, and mPWP was greater than 13 mm Hg despite the heart failure therapy. The nonpulmonary congestion group (11 patients) had no pulmonary congestion or edema, and mPWP was lower than 10 mm Hg. Histograms of pulmonary CT numbers were graphed to a set region of interest (ROI) on transverse CT images in all subjects; then changes of pulmonary CT numbers when pulmonary congestion or edema occurred were estimated from those histograms. We found that when severe pulmonary congestion or edema occurred in 6 patients with severe left heart failure, the pulmonary CT numbers within the ROI rapidly increased from -650 to -750 Hounsfield units (HU). We defined the amount ratio between the pixels (pixel counts between -650 and -750 HU within these R0Is) and the pixels (pixel counts between -300 and -950 HU) of the CT number (which were all pixels composing these R0Is) x100(%) as "%PXL." %PXL showed a linear correlation with mPWP. Compared with the %PXL in the normal group, the %PXL in the pulmonary congestion group was significantly higher than that in the normal group (p<0.05, p<0.01, p<0.001) in all lung fields. Similarly, compared with the %PXL in the normal group, %PXL in the nonpulmonary congestion group was significantly higher than that in the normal group in the middle and lower lung fields (p<0.05, p<0.01) in the posterior field. From these results, we concluded that %PXL was a good index to identify abnormal water content usually not recognizable by routine chest radiograph in the lungs.

Adult↗
PubMed1996

Vitamin A is involved in estrogen-induced cell proliferation but not in cytodifferentiation of the chicken oviduct.

We examined vitamin A-deficient chicks to determine whether vitamin A affects the estrogen-induced development of the chick oviduct. When oviduct development was stimulated for 5 days with the synthetic estrogen, diethylstilbestrol, the wet weight of the oviduct in vitamin A-deficient chicks was only half that in control chicks. The DNA content in this tissue showed that the decreased oviduct weight in the vitamin A-deficient chicks was caused by the decreased proliferation of oviduct cells. However, the estrogen-induced expression of the ovalbumin gene was not affected by the vitamin A deficiency, suggesting that estrogen-induced cytodifferentiation is not affected by vitamin A. To clarify the vitamin A action on estrogen-induced development in the oviduct, transcripts of nuclear estrogen receptor (ER) and all-trans-retinoic acid (RAR alpha, beta and gamma) receptors, which exert the effects of estrogen and vitamin A, were measured. The ER, RAR alpha and RAR beta genes, but not that of RAR gamma, were expressed during oviduct development, indicating that estrogen and vitamin A may control the expression of target genes through their cognate receptors. Thus, we have shown that vitamin A is involved in estrogen-induced cell proliferation but not in cytodifferentiation of the chicken oviduct.

Animals↗
PubMed1996

Familial occurrence of electrocardiographic abnormalities of the Brugada-type.

Electrocardiographic abnormalities were pointed out in a 51-year-old Japanese male whose major complaint was dizziness. His electrocardiogram showed a complete right bundle branch block, and a prolonged His bundle-ventricle (HV) interval of 100 msec. Two members of his family died of heart disease and 3 members, including a case of sudden death, presented an abnormal electrocardiogram of the Brugada-type with persistent ST segment elevation in the right precordial leads and right bundle branch block. The signal-averaged examination was made in the children of cases that died with the diagnosis of sudden death. Four cases showed a tendency of delay in the HV interval and a positive finding in the late potential. Further studies are necessary to clarify the relationship between electrocardiographic abnormalities of the Brugada-type and atrioventricular conduction disorder as well as to clarify the genetic basis of this disorder.

Adolescent↗
PubMed1996

The distribution and architecture of lymphatic vessels in the rat stomach as revealed by an enzyme-histochemical method.

Enzyme-histochemical methods of staining for 5'-nucleotidase (5'-Nase) and alkaline phosphatase (ALPase) were successfully applied to study the distribution and architecture of lymphatic vessels and their relationships to blood vessels in the rat stomach. Extensively lymphatic capillary networks were found in the gastric wall, but there were significant differences in their extent, pattern, distribution and structure in the four different zones: esophagus-stomach (E-S), forestomach-corpus (F-C), corpus-antrum (C-A) and antrum-duodenum (A-D). 5'-Nase-ALPase double staining revealed that the 5'-Nase-positive lymphatic vessels run in close proximity to ALPase-positive arteries and veins. The fine blood capillary network was located superficially to the lymphatic network within the same layer in the gastric wall. The abundant lymphatic network located in the deep lamina propria and the lamina muscularis mucosa was always closely associated with the base of the lowest gastric glands, and yet no interglandular lymphatic capillaries were encountered in the corpus or antrum. In contrast, fewer lymphatic capillaries were present in the lamina propria beneath the squamous epithelium of the forestomach. The distribution of the well-developed lymphatic networks with valve-like structures in the submucosa and subserosa exhibited typical features, i.e., the distribution was annular in the submucosa and fan-shaped in the subserosa in the antrum near the duodenum. Open junctions of lymphatic endothelial cells were seen in the deep lamina propria and submucosa. Collecting lymphatics containing valves were mainly located deep in the submucosa and subserosa. The deep lamina propria and submucosa may play a key role in lymph formation and interstitial tissue fluid homeostasis as well as in pathological processes in certain diseases. The present findings obtained by interstitially injecting ultra-fine carbon particle suspensions or Evans blue showed that a great deal of lymph drained into the lymphatics accompanying the left gastric artery. The existence of a forestomach may explain the complicated organization and constitution of lymphatic networks in the rat stomach.

Animals↗
PubMed1996

Use of a split dura for revascularization of ischemic hemispheres in moyamoya disease.

A new technique of indirect revascularization using the dural arterial supply to provide donor vessels is presented together with the results of an assay performed to determine the angiogenic activity of the dura. At surgery, a portion of the dura near the branches of the middle meningeal artery was split into outer and inner layers, and the split surface of the outer layer was attached to the cortical surface. This procedure, combined a with standard encephaloduroarteriosynangiosis, was applied to 25 hemispheres in 18 patients with pediatric moyamoya disease (mean age 6 years). All of the patients were symptom free by 1.5 years after surgery. The follow-up period ranged from 1 to 12 years (mean 6.5 years). Thirteen (81%) of 16 patients were able to lead normal lives and three were mildly handicapped due to mental retardation that existed preoperatively. Postoperative superselective angiograms demonstrated effective cortical revascularization through the dural arteries as well as from the scalp arteries. A histological study of the dura in cases of moyamoya disease showed an increased number of blood vessels in the outer layer. Angiogenic activity determined by chorioallantoic membrane assay was higher in the split surface of the dura than in the internal surface of the dura (the natural interface between the dura and cortex). The split duroencephalosynangiosis described in this report is a useful addition to indirect revascularization techniques, allowing extension of the area of revascularization in the ischemic hemispheres of patients with moyamoya disease.

Brain Ischemia↗
PubMed1996

Bacterially expressed rat retinol-binding protein is functional for retinol and transthyretin bindings.

Retinol-binding protein (RBP) was expressed in Escherichia coli using the cDNA for rat RBP, and characterized. The expressed RBP was fused to maltose-binding protein (MBP) at the N-terminal end (MBP-RBP), and MBP was enzymatically removed from the MBP-RBP with proteinase factor Xa. The binding of retinol and transthyretin (TTR) to the recombinant RBP was monitored by means of gel filtration. The recombinant RBP specifically bound to retinol with an affinity similar to that of purified RBP from rat serum. Furthermore, the retinol-bound recombinant RBP formed hetero-complexes with TTR similar to RBP. Thus, the results showed that the recombinant RBP expressed in E. coli is as functional as serum RBP in terms of retinol and TTR bindings.

ATP-Binding Cassette Transporters↗