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S Kato

Publications and source records attributed to S Kato.

At least 649 records · Page 36Linked to original sources
PubMed1997

Cytotoxin genes of Helicobacter pylori in chronic gastritis, gastroduodenal ulcer and gastric cancer: an age and gender matched case-control study.

Helicobacter pylori (H. pylori) infection is involved in many gastrointestinal diseases, such as chronic gastritis (CAG), peptic ulcer and gastric cancer (GCA). Both host factors and H. pylori strain differences may contribute to differences in the diseases. Thus, we conducted an age and gender matched case-control study of 35 patients each with CAG, gastric ulcer (GUL), duodenal ulcer (DUL) and gastric cancer (GCA) to examine the role of strain differences of the H. pylori cytotoxin genes cagA and vacA in these diseases. We employed polymerase chain reaction to examine the gastric juice for H. pylori DNA. The test was positive for 26 (74.3%) CAG, 29 (82.9%) GUL, 28 (80.0%) DUL and 27 (77.1%) GCA patients, showing no statistically significant difference among the diseases (P = 0.84). cagA and vacA genes (picked up by using a vacA1 + vacA2 primer pair which detected non-variable regions of the vacA gene) were detected by PCR in the H. pylori DNA-positive cases as follows: CAG, 92.3% and 76.9%; GUL, 100% and 86.2%; DUL, 89.3% and 89.3%; GCA, 92.6% and 85.2%, respectively. No statistically significant differences were found in the frequencies of these cytotoxin genes in H. pylori-positive cases among the various gastric diseases (P = 0.39 for cagA and P = 0.64 for vacA).

Adult↗
PubMed1997

PGE2 inhibits glucose uptake in isolated villous epithelial cells of the ovine small intestine.

This study was designed to clarify whether PGE2 directly inhibits glucose absorption in villous cells. For this purpose, isolated villous epithelial cells of the ovine small intestine were used, and the uptake of 14C-labelled glucose in the absorptive epithelial cells was measured in the presence and absence of 0.2 mM phlorizin or 10 microM PGE2. In isolated villous epithelial cells of the small intestine in sheep, net glucose absorption was reduced by 68.2% in the presence of phlorizin. This result indicates that most of the glucose in ruminants is absorbed by the specific transporter SGLT1, which is sensitive to phlorizin. PGE2 decreased glucose absorption by 26.5% in isolated villous epithelial cells in sheep, although this glucose absorption did not change in the presence of phlorizin. This result clearly indicates the PGE2 inhibits the phlorizin-sensitive glucose absorptive process through direct action on the villous cells of ruminants.

Animals↗
PubMed1997

Analysis of pathogenic elements involved in gastric lesions induced by non-steroidal anti-inflammatory drugs in rats.

Pathogenesis of gastric damage induced by non-steroidal anti-inflammatory drugs (NSAID) involves multiple elements, such as deficiency of prostaglandins (PG), gastric hypermotility, neutrophil activation and luminal acid. The present study was performed to examine the effects of these elements, either alone or in combination, on the rat gastric mucosa and investigate which element is most closely associated with the gastric ulcerogenic response to NSAID. The following treatments were used to express various pathogenic elements: (i) a low dose of indomethacin (IM) to cause PG deficiency; (ii) 2-deoxy-D-glucose (2DG) to induce gastric hypermotility and acid secretion; (iii) histamine to induce acid hypersecretion; and (iv) n-formyl-Met-Leu-Phe (fMLP) to elicit neutrophil activation. When rats fasted for 18 h were subjected to each treatment alone, only 2DG caused slight macroscopic damage in the gastric mucosa within 4 h. Indomethacin showed over 90% inhibition of mucosal PG generation and fMLP increased myeloperoxidase activity four-fold greater than normal values, yet either of these treatments alone did not cause any damage in the stomach. However, the combination of IM with 2DG or His provoked severe lesions in the stomach or the duodenum, respectively, while fMLP did not modify or potentiate the mucosal ulcerogenic response to other treatments. We conclude that among various pathogenic elements only gastric hypermotility is sufficient, by itself, to induce mild damage in the mucosa, that PG deficiency may be critical in the increase of mucosal susceptibility to injury and that neutrophil activation alone is not ulcerogenic in the gastric mucosa nor does it potentiate the ulcerogenic effect of other elements. Luminal acid may be a prerequisite for later extension of damage to severe lesions.

Animals↗
PubMed1997

Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress.

Oxidative 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 P450 in the microsomes and the molybdo-flavoenzyme xanthine oxidase in the cytosol. This review shows the putative role of ethanol-induced disturbances in iron metabolism in relation to iron as a pro-oxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Many previous studies suggest a role for active oxygens in ethanol-induced mitochondrial dysfunction in hepatocytes. Recent studies in our laboratory in the Department of Internal Medicine, Keio University, using a confocal laser scanning microscopic system strongly suggest that active oxidants generated during ethanol metabolism produce mitochondrial membrane permeability transition in isolated and cultured hepatocytes. In addition, acetaldehyde, ethanol consumption-associated endotoxaemia and subsequent release of inflammatory mediators may cause hepatocyte injury via both oxyradical-dependent and -independent mechanisms. These cytotoxic processes may lead to lethal hepatocyte injury. Investigations further implicate the endogenous glutathione-glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocytes exposed to ethanol.

Acetaldehyde↗
PubMed1997

Fas antigen expression and its relationship with apoptosis in transplanted kidney.

A total of 244 human renal biopsy cases were examined under the following three categories of renal disease: (i) transplanted kidney (TK; 127 cases); (ii) primary glomerular disease (GD; 88 cases); and (iii) others (29 cases). In these cases, the immunohistochemical distribution of apoptosis-related proteins (Fas antigen and bcl-2 protein) was investigated. Despite no detection in normal kidney tissues, Fas antigen was highly expressed in the tubular epithelium, indicating that Fas antigen expression was induced on the tubular epithelium in human renal disease. Furthermore, in TK Fas antigen expression was significantly frequent in acute rejection including acute rejection borderline (9/43 cases) and acute rejection stages I-III (10/28 cases), as compared with that in control cases (no rejection, 1/32 cases). Fragmented DNA stained with in situ nick end-labeling was predominantly detected in the tubular epithelium in 6 of 48 cases (23 with transplanted kidney and 21 with glomerular disease). Characteristic nuclear apoptotic changes were detected in the tubular epithelium by light microscopy. These results indicate that apoptosis takes place mainly in the renal tubular epithelium. The present experimental study revealed that Fas mRNA transcripts were induced in human renal cell line by interferon-gamma. This suggests that in situ induction of Fas antigen in the tubular epithelium is mediated, at least in part, by cytokines in association with inflammatory lymphocytic infiltrates. It was also revealed that anti-Fas monoclonal antibody induced apoptosis of the renal cell line through stimulation with interferon-gamma. Taken together, the results suggest that induced expression of Fas antigen on the tubular epithelium might play an important role in apoptosis under acute renal graft rejection.

Adult↗
PubMed1997

Fluoride profiles in the cementum and root dentine of human permanent anterior teeth extracted from adult residents in a naturally fluoridated and a non-fluoridated area.

OBJECTIVES: To determine the effect of water fluoride concentration on the fluoride profile across the entire thickness of the cementum and root dentine of human permanent anterior teeth in adults. SUBJECTS: Twenty-eight human permanent anterior teeth from individuals aged from 30 to over 60 years were studied. SETTING: Teeth were obtained from a natural high-fluoride area (West Hartle-pool, UK; 1.0-1.3 ppm F in drinking water, WHP) and the other from a non-fluoridated naturally low fluoride area (Leeds, UK; 0.1 ppm F in drinking water, LDS). DESIGN: Cementum and root dentine were sampled using an abrasive micro-sampling technique from the cementum surface to the pulpal surface of root dentine. RESULTS: Fluoride concentration was higher in tooth roots (the cementum and dentine) taken from the naturally fluoridated area (WHP) than from the non-fluoridated area (LDS). Age and average fluoride concentration showed a positive correlation in WHP dentine, middle region of the root (r = 0.78, P < 0.001) and in the apical region of the root (r = 0.61, P < 0.05). WHP cementum had the strongest fluoride concentration correlation with age in the cervical region of the root (r = 0.67, P < 0.01). An analysis of variance (ANOVA) showed that the area (water fluoride content), age and number of years lived in the area combined with total age were significant. CONCLUSIONS: The fluoride content of cementum and root dentine in adult residents is related to fluoride content in drinking water.

Adult↗
PubMed1997

Role of CD14 molecules in internalization of Actinobacillus actinomycetemcomitans by macrophages and subsequent induction of apoptosis.

We report the evidence for apoptosis in J774.1 cells by the periodontopathic bacterium Actinobacillus actinomycetemcomitans, suggesting that the ability of A. actinomycetemcomitans to promote apoptosis might be important in the initiation and development of periodontitis. In this study, we examined the role of macrophage CD14, anchored by a glycerophosphatidylinositol tail, in the induction of apoptosis by A. actinomycetemcomitans infection by using the parent J774.1 cells and CD14-defective mutant (LR-9) cells. A small number of A. actinomycetemcomitans Y4 cells inside the LR-9 cells compared with the number in J774.1 cells was detected by confocal scanning microscopy. We found that LR-9 cells showed a weak cytotoxic effect after being infected with A. actinomycetemcomitans Y4. Apoptotic cell death of LR-9 cells infected with A. actinomycetemcomitans Y4, compared with that of the parent J774.1 cells was almost undetectable, as shown by the proportion of fragmented DNA in agarose gel electrophoresis and by the terminal deoxynucleotidyl transferase-mediated dUTP end-labeling method. Flow cytometric cell cycle analysis of J774.1 cells infected with A. actinomycetemcomitans Y4 revealed the increased percentage of apoptotic cells with hypodiploid DNA. However, LR-9 cells infected with A. actinomycetemcomitans Y4 showed no increase in population of apoptotic nuclei compared with the noninfected cells. These findings suggest that the CD14 molecules may contribute to the phagocytosis of A. actinomycetemcomitans by J774.1 cells and regulate, at least in part, apoptotic cell death of macrophages infected with A. actinomycetemcomitans.

Actinobacillus Infections↗
PubMed1997

PACAPs stimulate duodenal bicarbonate secretion at PACAP receptors in the rat.

We investigated the effects of pituitary adenylate cyclase-activating polypeptides (PACAPs) on gastroduodenal HCO(3)- secretion in anesthetized rats and characterized their effects by comparison with the effects of vasoactive intestinal polypeptide (VIP). Under urethan anesthesia, a rat proximal duodenal loop or a rat stomach mounted in an ex vivo chamber (in the absence of acid secretion) was perfused with saline, and HCO(3)- secretion was measured at pH 7.0 using a pH-stat method and by addition of 10 mM HCl. Intravenous injection of PACAP-27 stimulated HCO(3)- secretion in a dose-dependent manner in the duodenum, but not in the stomach, although this peptide had no effect on duodenal HCO(3)- secretion after intracisternal administration. The duodenal HCO(3)- stimulatory action was similarly observed after intravenous administration of PACAP-38 and VIP, and the potency of action was in the following order: PACAP-27 > PACAP-38 = VIP. The duodenal HCO(3)- stimulatory action of PACAP-27 was potentiated by pretreatment with 3-isobutyl-1-methylxanthine, similar to that of prostaglandin E2, and was significantly attenuated by PACAP-(6--27) (PACAP antagonist) or Ac-Tyr1,D-Phe2-VIP (VIP antagonist) but was not affected by bilateral vagotomy or prior administration of atropine, verapamil, and indomethacin. Forskolin, the stimulator of adenylate cyclase, also increased HCO(3)- secretion in the duodenum, but not in the stomach. These results suggest that 1) PACAP is a potent stimulator of HCO(3)- secretion in the duodenum, but not in the stomach, and may be involved in the peripheral regulation of duodenal HCO(3)- secretion, 2) this action is mediated by adenosine 3',5'-cyclic monophosphate, probably through PACAP and VIP receptors, and 3) adenosine 3',5'-cyclic monophosphate is a mediator in duodenal, but not in gastric, HCO(3)- secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Role of nitric oxide in mucosal blood flow response and the healing of HCl-induced lesions in the rat stomach.

The role of nitric oxide (NO) in the gastric mucosal blood flow response and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and 1 h later they were fed normally. After induction of gastric lesions, they were repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with re-epithelialization. Repeated administration of L-NAME but not aminoguanidine significantly delayed the healing of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response, increased the luminal H+ loss, and totally inhibited the mucosal hyperemic response associated with luminal acid loss in the damaged mucosa. In addition, the deleterious influences of L-NAME on the mucosal blood flow response and the healing of gastric lesions were significantly antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the damaged mucosa. NO mediating such responses and participating in the healing aspect of gastric lesions may be produced by the constitutive type of NO synthase.

Animals↗
PubMed1997

Inhibition of neutrophil elastase-induced interleukin-8 gene expression by urinary trypsin inhibitor in human bronchial epithelial cells.

BACKGROUND: Urinary trypsin inhibitor (UTI), a potential inhibitor for proteinases including neutrophil elastase (NE), trypsin, plasmin, cathepsin B and H has been used for the treatment of lung diseases with the absence of side effects in Japan. METHODS: In this study, we investigated the inhibitory effects of UTI on both purified NE and NE activities present in bronchoalveolar fluids from patients with chronic bronchitis. We also investigated the inhibitory capacity of UTI with regard to NE-induced interleukin-8 gene expression in human bronchial epithelial cells by Northern analyses. RESULTS: UTI inhibited NE activities in bronchoalveolar lavage fluid from patients with chronic bronchitis and of the purified enzyme. In addition, UTI inhibited NE-induced interleukin-8 gene expression and protein secretion in a human bronchial epithelial cell line. CONCLUSIONS: Our results suggest that UTI is applicable to patients with a variety inflammatory lung diseases in which NE plays a pivotal role.

Bronchi↗
PubMed1997

Cerebral aneurysms in the elderly in Yamaguchi, Japan. Analysis of the Yamaguchi Data Bank of Cerebral Aneurysm from 1985 to 1995.

BACKGROUND AND PURPOSE: The number of elderly people is markedly increasing in Japan. We have investigated the epidemiology and management outcome of cerebral aneurysms in elderly patients aged > or = 70 years. METHODS: A total of 3100 patients were enrolled in the Yamaguchi Data Bank of Cerebral Aneurysm between 1985 and 1995. Of these, 598 with ruptured cerebral aneurysms and 120 with unruptured cerebral aneurysms were elderly (ie, aged > or = 70 years). RESULTS: The number of elderly patients with cerebral aneurysms has markedly increased since 1991, and in 1995 approximately 30% of all patients with cerebral aneurysms were elderly. In cases of ruptured cerebral aneurysms, the proportion of patients with severe neurological grade did not change and that with an unfavourable outcome did not decrease throughout the 11 years. The proportion of patients with severe neurological grade in the elderly group was higher than in the younger group (< 70 years), and the management outcome of elderly patients for each neurological grade on admission was worse than that of younger patients (P < .01). However, the incidence rate of symptomatic cerebral vasospasm and rebleeding was the same for the two age groups. Eventually, 60.4% of all elderly patients with ruptured cerebral aneurysms had an unfavorable outcome. In cases of unruptured cerebral aneurysms, 63.3% of the selected elderly patients were surgically treated, and the surgical morbidity and mortality rates were 26.3% and 4.0%, respectively. These rates were nonsignificantly higher than those for younger patients. CONCLUSIONS: The number of elderly patients with cerebral aneurysms has markedly increased in Yamaguchi. Because of the unsatisfactory management outcome of ruptured cerebral aneurysms and surgical outcome of unruptured cerebral aneurysms in elderly patients during the 11-year period, we propose the treatment of unruptured cerebral aneurysms at a younger age and the use of a screening system to detect these subjects.

Age Distribution↗
PubMed1997

Evaluation of biological responses to polymeric biomaterials by RT-PCR analysis. II: Study of HSP 70 mRNA expression.

In order to investigate how cells recognize biomaterials, mRNA that was expressed in attached HeLa S3 cells on various substrates was evaluated. As culture substrates, cellulose, ethylene-vinyl alcohol copolymer (EVAL), nylon, tissue culture polystyrene (TCPS), high-density polyethylene (PE), silicone rubber, and tetrafluoroethylene-hexafluoropropylene copolymer (6F) were used. HeLa S3 cells were cultured on these substrates for 24 h. The expressed HSP 70s mRNA was then isolated and detected using the RT-PCR method. As a result, the expression of HSP 70B mRNA was largely induced in cells that adhered to hydrophilic surfaces. On the other hand, on hydrophobic surfaces, the HSP 70B mRNA expression was low. It is concluded that HSP 70B mRNA expression is sensitive to differences in the hydrophilicity-hydrophobicity of the substrates.

Biocompatible Materials↗
PubMed1997

Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury.

Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple epithelia, including bronchial epithelial cells (BEC). Since CK19 is released from injured bronchial epithelium, we investigated the levels of CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients with chronic airway inflammatory diseases (CAID) using an enzyme-linked immunosorbent assay (ELISA). Included in our test group were four cases of chronic bronchitis, three cases of bronchiectasis, and one case of diffuse panbronchiolitis. There were also 15 control subjects (five asymptomatic smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/- 0.8 pg/ml, respectively). In contrast, significantly high levels of CK19 were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p < 0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations in BALF correlated significantly with the number of neutrophils (r = 0.722, p < 0.01) but not with the numbers of macrophages or lymphocytes in BALF. BALF from patients with CAID contained high levels of neutrophil elastase (NE) activity, suggesting that NE might be an important stimulus for the release of CK19 from BEC. To prove this, we incubated BET-1A cells, a human immortalized bronchial epithelial cell line, both in the absence and the presence of inflammatory mediators (including NE, tumor necrosis factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the concentration of CK19 fragments in the culture supernatants with ELISA. BET-1A cells released CK19 fragments into their culture supernatants after treatment with NE but not after treatment with TNF or hydrogen peroxide. Further, we demonstrated that CK19 cleaved by NE could not be detected by ELISA. Our results suggest that CK19 measurement in BALF is useful for assessing the presence of bronchial epithelial injuries.

Adult↗
PubMed1997

A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) characterized by early-onset hypertension and hypokalemia is due to congenital deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). Two isoforms of human 11 beta HSD are known, and the type 2 isoform (11 beta HSD2) has been recently shown to be responsible for AME. In this study we have analyzed the 11 beta HSD2 gene of a Japanese patient with AME. PCR amplification and subsequent nucleotide sequencing of the 11 beta HSD2 gene from the patient and his family members revealed that the patient has a compound heterozygous mutation of this gene. In 1 allele, an undescribed single nucleotide transition in codon 208 in exon 3 resulted in a substitution of arginine to histidine (CGC to CAC: R208H). In the other allele, a deletion of 3 nucleotides in codons 337-338 in exon 5 resulted in a substitution of arginine to histidine and a deletion of tyrosine residue (CGCTAT to CAT: R337H, delta Y338), which has been previously shown to abolish 11 beta HSD2 enzyme activity. A chloramphenicol acetyltransferase assay-based expression study involving the mineralocorticoid receptor indicated that the novel R208H mutation eliminates the enzymatic activity of 11 beta HSD2. From the genetic analysis of 50 healthy subjects, the novel R208H mutation was unlikely to be due to polymorphism. Together, these results indicate that this patient is a compound heterozygote for the mutation in the 11 beta HSD2 gene (R208H and R337H, delta Y338) and that these mutations inactivate the 11 beta HSD2 function and give rise to clinically manifest AME.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Electronic and structural requirements for metabolic activation of butylated hydroxytoluene analogs to their quinone methides, intermediates responsible for lung toxicity in mice.

Previous studies have shown that butylated hydroxytoluene (BHT) undergoes oxidation by cytochrome P450 to form BHT-quinone methide. BHT-quinone methide is probably responsible for BHT-induced lung damage in mice. In this study, we calculated the MO parameters for BHT analogs and the corresponding quinone methide intermediates. Except for the analogs with structures that form a highly sterically hindered quinone methide, correlations could be established between the lung toxicity in mice and electronic charges on the hydroxyl oxygen and 4-carbon atoms of BHT analogs. The same toxicity could also be correlated to the difference between the heat of formation of the quinone methide intermediates and the parent BHT analogs, and to the electronic charge on the carbonyl oxygen atom of the quinone methides. These results suggest that the metabolic activation of BHT analogs to their quinone methide intermediates is energetically dependent on the oxidation of the aromatic pi-electron system, and that the toxic potency of BHT analogs is controlled by protonation of the oxygen atom of the quinone methides. These electronic features provide further evidence of the importance of the quinone methide intermediates in the mechanism of lung toxicity induced by BHT analogs.

Animals↗