PubMed Health⌕ Search

Biomedical subjects

Akira Andoh

Publications and source records attributed to Akira Andoh.

At least 73 records · Page 4Linked to original sources
PubMed2003

N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis.

Dietary fat is an important factor involved in the pathogenesis of inflammatory bowel disease (IBD). It remains unclear how n-3 and n-6 fatty acids modulate intestinal inflammation. In this study, we investigated the effects of n-3 and n-6 fatty acid-rich diets on trinitrobenzene sulfonic acid (TNBS)-induced enteritis. The rats were fed an n-3 or n-6 rich-diet for 12 days, and then starved for the following 2 days. An intraileal injection of TNBS was administered, and TNBS-enteritis subsequently developed. Macroscopic and histological examination was performed after 24 h. Serum cytokine levels were determined by ELISA. The n-6 fatty acid-rich diet markedly enhanced mucosal damage as compared to the n-3 fatty acid-rich diet. The damage score was significantly higher in the n-6 fatty acid-rich diet group (P<0.05). Histological changes in the mucosa were more severe in the n-6 fatty acid-rich diet group than in the n-3 fatty acid-rich group. Serum IL-6 levels were significantly higher in the n-6 fatty acid-rich diet group than in the n-3 fatty acid-rich group (P<0.05). On the other hand, there were no differences in serum TNF-alpha levels. The n-3 fatty acid-rich diet effectively reduced early mucosal inflammation in TNBS enteritis. The effects of the n-3 fatty acids were associated with blockage of mucosal IL-6 secretion. Our data suggest that n-3 fatty acid-rich diet may be applicable for enteral nutrition in the treatment of IBD patients.

Animal Feed↗
PubMed2002

Extracellular signal-regulated kinases 1 and 2 participate in interleukin-17 plus tumor necrosis factor-alpha-induced stabilization of interleukin-6 mRNA in human pancreatic myofibroblasts.

In human pancreatic myofibroblasts, interleukin (IL)-17 markedly enhances tumor necrosis factor (TNF)-alpha-induced IL-6 secretion through the induction of IL-6 mRNA stabilization. Induced stability of IL-6 mRNA was markedly decreased by the inhibitors of extracellular signal-regulated kinase (ERKs), PD98059 and U0216. This indicates that activation of the ERK pathway is involved in the induction of IL-6 mRNA stabilization by IL-17 plus TNF-alpha.

Cells, Cultured↗
PubMed2002

IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts.

IL-17 enhances the TNF-alpha-induced IL-6 and IL-8 secretion in human colonic subepithelial myofibroblasts. In this study, we investigated how IL-17 modulates RANTES secretion in these cells. TNF-alpha potently induced RANTES secretion, but IL-17 dose-dependently inhibited the TNF-alpha-induced RANTES secretion. This was also observed at the mRNA level. Even after pretreatment with TNF-alpha for 12 h, the inhibitory effect of IL-17 was detectable. IL-17 did not affect the TNF-alpha-induced stability of the RANTES gene. IL-17 significantly decreased the TNF-alpha-induced increase in RANTES promoter activity, and IL-17 actually blocked the TNF-alpha-induced RANTES gene transcription. EMSAs demonstrated that IL-17 did not modulate the TNF-alpha-induced NF-kappaB DNA-binding activity, but markedly decreased TNF-alpha-induced IFN regulatory factor-1 (IRF-1) DNA-binding activity. Because cooperation between NF-kappaB and IRF-1 is important in the TNF-alpha-induced RANTES gene expression, the major mechanism mediating the inhibitory effect of IL-17 may be achieved by the inhibition of IRF-1 DNA-binding activity.

Base Sequence↗
PubMed2002

Analysis of alpha-amylase-derived pyridylamino-dextran sulfate oligomers by the combination of size-exclusion and reversed-phase high-performance liquid chromatography.

In a previous study, we reported a novel method for the separation and quantification of a strong negatively charged material, dextran sulfate sodium (DSS), using fluorometric labeling with 2-aminopyridine and size-exclusion high-performance liquid chromatography. In the present study, we developed a method for the separation of pyridylamino-DSS (PA-DSS) using reversed-phase high-performance liquid chromatography (RPLC). In vitro enzymatic degradation of the PA-DSS was carried out using alpha-amylase. In RPLC, depolymerized PA-DSS was eluted on the basis of molecular mass (in the order pentamer, trimer, dimer, and monomer of PA-DSS) and separations were more sharply than in size-exclusion chromatography. The combination of RPLC and size-exclusion chromatography also separated depolymerized PA-DSS as effectively as RPLC alone.

Chromatography, Gel↗
PubMed2002

IL-6 secretion by human pancreatic periacinar myofibroblasts in response to inflammatory mediators.

There is increasing evidence that IL-6 plays an important role in the pathophysiology of acute pancreatitis via its broad proinflammatory actions. To identify the local biosynthetic site for IL-6 in human pancreas, we investigated IL-6 secretion in human pancreatic periacinar myofibroblasts. IL-6 secretion was determined by ELISA and Northern blotting. The activation of NF-kappaB was assessed by EMSA. The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6 secretion was rapidly induced by IL-17, IL-1beta, and TNF-alpha. EMSAs demonstrated that IL-17, IL-1beta, and TNF-alpha induced NF-kappaB activation within 1.5 h after stimulation, and a blockade of NF-kappaB activation by the pyrrolidine derivative of dithiocarbamate and tosyl-phe-chloromethylketone markedly reduced the IL-17-, IL-1beta-, or TNF-alpha-induced IL-6 gene expression. Furthermore, IL-17, IL-1beta, and TNF-alpha induced a rapid activation of extracellular signal-related kinase p42/44 and p38 MAPKs, and specific MAPK inhibitors (SB203580, PD98059, and U0216) significantly reduced IL-17-, IL-1beta-, or TNF-alpha-induced IL-6 secretion, indicating the role of MAPKs in the induction of IL-6. The combination of either IL-17 plus IL-1beta or IL-17 plus TNF-alpha enhanced IL-6 secretion and IL-6 mRNA expression; in particular, the effects of IL-17 plus TNF-alpha were much stronger than those induced by IL-17 plus IL-1beta. TNF-alpha-induced IL-6 mRNA degraded rapidly at any concentrations, and the combination of IL-17 and TNF-alpha markedly enhanced IL-6 mRNA stability. This indicates that the effects of IL-17 plus TNF-alpha were regulated at the post-transcriptional level. In conclusion, pancreatic periacinar myofibroblasts secreted a large amount of IL-6 in response to proinflammatory cytokines. These cells might play an important role in the pathogenesis of acute pancreatitis via IL-6 secretion.

Cells, Cultured↗
PubMed2002

Intestinal subepithelial myofibroblasts in inflammatory bowel diseases.

Colonic subepithelial myofibroblasts (SEMFs) may play a role in the regulation of a number of epithelial cell functions and in the mucosal repair process. In this study, we evaluated the changes in alpha-smooth muscle actin (SMA)- and vimentin-positive SEMFs in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Tissue samples were surgically obtained from patients with active ulcerative colitis (UC) (n = 5) and active Crohn's disease (CD) (n = 5). Normal intestinal tissues were also obtained (n = 5). The SMA and vimentin expression was evaluated by standard immunohistochemical procedures. In normal intestinal mucosa, SMA- and vimentin-positive SEMFs were located immediately subjacent to the basement membrane, juxtaposed against the bottom site of the epithelial cells. In the inflamed mucosa of active UC patients, there were relatively more SMA-positive cells compared with normal mucosa. In particular, the increase in SMA-positive cells was greatest at the marginal area of deep ulcers of UC patients. In active CD mucosa, SMA-positive cells were increased in all samples, and a marked increase was observed in two samples. The number of SMA-positive SEMFs was relatively higher in CD mucosa than in UC mucosa. An [3H]thymidine incorporation study demonstrated that platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor (bFGF), and insulin-like growth factor (IGF)-I significantly increased the uptake of [3H]thymidine into isolated SEMFs. In particular, PDGF had a strong stimulatory effect. We concluded that colonic SEMFs may play an important role in the repair process of IBD.

Actins↗
PubMed2002

Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial.

BACKGROUND: Germinated barley foodstuff (GBF) is a prebiotic foodstuff that effectively increases luminal butyrate production by stimulating the growth of protective bacteria. In the first pilot study, GBF has been shown to reduce both clinical activity and mucosal inflammation in ulcerative colitis (UC). The aim of this study was to investigate the efficacy of GBF in the treatment of UC in a multicenter open control trial. METHODS: Eighteen patients with mildly to moderately active UC were divided into two groups using a random allocation protocol. The control group (n = 7) were given a baseline anti-inflammatory therapy for 4 weeks. In the GBF-treated group (n = 11), patients received 20-30 g GBF daily, together with the baseline treatment, for 4 weeks. The response to the treatments was evaluated clinically and endoscopically. Fecal microflora were also analyzed. RESULTS: After 4 weeks of observation, the GBF-treated group showed a significant decrease in clinical activity index scores compared with the control group (P < 0.05). No side effects related to GBF were observed. GBF therapy increased fecal concentrations of Bifidobacterium and Eubacterium limosum. CONCLUSIONS: Oral GBF therapy may have the potency to reduce clinical activity of UC. We believe that these results support the use of GBF administration as a new adjunct therapy for UC.

Adult↗
PubMed2002

Immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in gastroesophageal reflux disease.

BACKGROUND: The aim of this study was to carry out an immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in endoscopic biopsy samples obtained using angled biopsy forceps. METHODS: The study was based on the examination of endoscopic esophageal biopsy specimens obtained from 46 patients with evidence of reflux and from 10 normal control subjects without clinical reflux. RESULTS: The percentage of samples containing the lamina propria was 5.7% using standard forceps ( n = 53) and 83.3% using the angled forceps ( n= 67). The use of angled forceps allowed the detection of inflammatory cell accumulation in the lamina propria even in patients with modified Los Angeles (LA) system grades N and M. In normal esophageal mucosa, Ki-67-positive cells were detected within the lower parts of the basal zone, and p21- and p27-positive cells were not detected. In samples from grade N and M patients, no histological changes were detectable by standard H&E staining. However, the area of Ki-67-positive cells was slightly expanded compared with normal mucosa, and p21- and p27-positive cells were clearly detectable from the lower to middle part of the epithelium. The area of Ki-67-, p21-, and p27-positive cells tended to expand upward in the epithelium with gastroesophageal reflux disease (GERD) severity based on the LA classification grading. CONCLUSIONS: The use of angled biopsy forceps allows the evaluation of inflammatory responses at the level of the lamina propria and makes it possible to assess the expression of cell cycle-regulating proteins in the entire epithelium. The evaluation of these responses may be helpful in the diagnosis of endoscopically negative GERD.

Basement Membrane↗
PubMed2002

Stem cell factor expressed in human gastric mucosa in relation to mast cell increase in Helicobacter pylori-infected gastritis.

We previously reported mast cell increases in H. pylori gastritis. To determine the mechanism, we investigated the kinetics of mast cells and mast cell growth factor (stem cell factor, SCF) in H. pylori-positive and -negative gastric mucosa. Biopsy specimens from 12 H. pylori-negative and 28 positive subjects were examined. Sections were stained for mast cells, proliferating cell nuclear antigen (PCNA), and SCF. Densities of mast cells, PCNA-positive mast cells, and SCF-positive cells were significantly greater in H. pylori-positive than -negative subjects. SCF was expressed in mast cells and fibroblasts. The density of SCF-positive fibroblasts increased in H. pylori-positive gastritis and decreased after cure of infection. SCF mRNA was detected in H. pylori-positive gastric mucosa. Fibroblasts isolated from the normal gastric mucosa expressed SCF mRNA after incubation with H. pylori water extract. SCF may be one of the factors for mast cell increase. Fibroblasts may participate in mast cell increase and inflammation in H. pylori infection.

Adult↗
PubMed2002

A new prebiotic from germinated barley for nutraceutical treatment of ulcerative colitis.

A germinated barley foodstuff (GBF) containing glutamine-rich protein and hemicellulose-rich fiber was made from brewer's spent grain, by physical isolation. Our previous studies demonstrated that GBF supported maintenance of epithelial cell populations, facilitated epithelial repair, and suppressed epithelial nuclear factor kappaB-DNA-binding activity through generating increased short-chain fatty acid (especially butyrate) production by luminal microflora, which includes Bifidobacterium and Eubacterium, thereby preventing experimental colonic injury. The fiber fraction also modulates stool water content because of its high water-holding capacity. The patients with mild to moderate active ulcerative colitis who had been unresponsive to or intolerant of standard treatment received 20-30 g GBF, feeding daily in a non-randomized, open-label fashion. At 4 weeks, this treatment resulted in a significant clinical and endoscopic improvement. The improvement was associated with an increase in stool butyrate concentrations. These results indicate that GBF feeding is a potentially new, attractive prebiotic treatment in patients with ulcerative colitis. The potency of GBF on modulating microflora, as well as the high water-holding capacity, may play an important role in treatment and prolongation of remission in ulcerative colitis.

Colitis, Ulcerative↗
PubMed2002

Inhibitory effects of the new anti-inflammatory agent, IS-741, on spontaneous colitis in HLA-B27/beta2-microglobulin transgenic rats.

BACKGROUND: A novel anti-inflammatory drug, IS-741, blocked the adhesion of inflammatory cells to microvascular endothelial cells both in vivo and in vitro. Transgenic rats expressing human leukocyte antigen (HLA)-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis, which resembles human inflammatory bowel disease. In the present study, the authors examined the efficacy of IS-741 against spontaneous colitis in HLA-B27 rats. METHODS: The HLA-B 27 rats were divided in two groups after the development of colitis. IS-741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days. RESULTS: The HLA-B27 rats treated with IS-741 remained healthy; the wet weight of the colon was significantly lower in the IS-741-treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and the submucosa in the control HLA-B27 rats, but these changes were attenuated in the IS-741-treated group. The mucosal damage score was also significantly reduced by treatment with IS-741. IS-741 significantly reduced the mucosal myeloperoxidase activity and mucosal cytokine-induced neutrophil chemoattractant-1 levels. IS-741 also reduced CD3-positive T-cell infiltration. CONCLUSION: IS-741 suppressed the spontaneous colitis that developed in HLA-B27 rats. Some of the actions of IS-741 may be associated with its inhibitory effects on the adhesion of neutrophils to endothelial cells. The findings from the present study suggest that IS-741 may be a useful new therapeutic agent for inflammatory bowel disease.

Animals↗
PubMed2002

Mast cells may not play a crucial role in the pathogenesis of experimental closed duodenal loop-induced pancreatitis in rats.

INTRODUCTION: Ws/Ws rats have a small deletion of the c-kit gene and are deficient in both mucosal-type mast cells and connective tissue-type mast cells. AIM: To investigate the role of pancreatic mast cells in the development of experimental closed duodenal loop (CDL)-induced pancreatitis using Ws/Ws rats. METHODOLOGY: Pancreatitis was induced by the CDL technique for 5 and 12 hours, and the subsequent ascites volume, wet pancreatic weight, pancreatic myeloperoxidase activities, and serum amylase levels were evaluated. The pancreatic tissue damage was also evaluated histologically. RESULTS: The CDL technique induced equally severe ascites, pancreatic edema and hyperemia, and hyperamylasemia in the Ws/Ws versus the control (+/+) rats. The microscopic mucosal damage score was also equivalent in the Ws/Ws and control (+/+) rats, and there were no significant differences in mucosal myeloperoxidase activity between the Ws/Ws and control (+/+) rats. CONCLUSION: These results indicate that mast cells may not be crucial for the development of CDL-induced pancreatitis.

Amylases↗
PubMed2002

IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts.

Colonic subepithelial myofibroblasts (SEMFs) may play a role in the modulation of mucosal inflammatory responses. We investigated the effects of interleukin (IL)-17 on IL-6 and chemokine [IL-8 and monocyte chemoattractant protein (MCP)-1] secretion in colonic SEMFs. Cytokine expression was determined by ELISA and Northern blotting. Nuclear factor kappa B (NF-kappaB) DNA-binding activity was evaluated by electrophortetic gel mobility shift assay (EMSA). The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6, IL-8, and MCP-1 secretions were rapidly induced by IL-17. IL-17 induced NF-kappaB activation within 45 min after stimulation. A blockade of NF-kappaB activation markedly reduced these responses. MAPK inhibitors (SB-203580, PD-98059, and U-0126) significantly reduced the IL-17-induced IL-6 and chemokine secretion. The combination of either IL-17 + IL-1beta or IL-17 + tumor necrosis factor (TNF)-alpha enhanced cytokine secretion; in particular, the effects of IL-17 + TNF-alpha on IL-6 secretion were much stronger than the other responses. This was dependent on the enhancement of IL-6 mRNA stability. In conclusion, human SEMFs secreted IL-6, IL-8, and MCP-1 in response to IL-17. These responses might play an important role in the pathogenesis of gut inflammation.

Antineoplastic Agents↗
PubMed2002

Oral administration of a product derived from Clostridium butyricum in rats.

Recent studies have suggested that short chain fatty acids (SCFAs) exert a therapeutic effect on some human and experimental animal diseases. Clostridium butyricum produces high levels of SCFAs in the gut lumen. The aim of the present study was to analyze the product derived from Clostridium butyricum in a culture system, and to develop methods to eliminate the odor derived from SCFAs in the product. Clostridium butyricum was incubated in CS medium for 24 h and subsequently in CS broth for 24 h. The suspension of Clostridium butyricum in the broth was centrifugated and the supernatant was analyzed. The results showed this product contained high levels of SCFAs, especially acetic acid and n-butyric acid. Many food materials were tested in order to eliminate the odor derived from SCFAs in the product. Of the food materials tested, yogurt was shown to most effectively eliminate the odor. Using a yogurt base, we prepared a special food additive. Use of the additive completely eliminated the odor of the product derived from Clostridium butyricum. Finally, we administered the product with the additive to Sprague-Dawley rats for 14 days. The rats grew normally for the duration of the experimental period. It is possible that this novel product with the additive exerts therapeutic effects on some gastointestinal disorders.

Acetic Acid↗
PubMed2002

Prebiotic treatment of experimental colitis with germinated barley foodstuff: a comparison with probiotic or antibiotic treatment.

There is increasing evidence that intestinal microflora play an important role in the pathogenesis of ulcerative colitis. Therefore, modification of the microflora by prebiotics, probiotics, and antibiotics may be a rational approach for controlling intestinal inflammation. Germinated barley food-stuff (GBF) is an insoluble mixture of glutamine-rich protein and hemicellulose-rich dietary fiber. GBF is utilized efficiently by Bifidobacterium, Lactobacillus, and Eubacterium and converted by them into lactate, acetate, and butyrate. These bacterial organic acids preserve a favorable intestinal condition. We have previously shown that GBF has attenuated intestinal inflammation in patients with ulcerative colitis and experimental colitis models through prebiotic actions. The aim of this study was to compare the effect of GBF with that of probiotics and antibiotics in an experimental colitis model. Colitis was induced by feeding male SD rats with a diet containing 3.0-3.5% dextran sodium sulfate (DSS). The therapeutic effect of oral administration of a prebiotic (GBF), probiotics (mixture of Lactobacillus and Clostridium butyricum), antibiotics (vancomycin, metronidazole), and the vehicle was determined by assessing clinical and pathological scores on day 6 after initiation of colitis. Butyrate concentrations in the cecal content were also determined. GBF treatment significantly reduced colonic inflammation as assessed by clinical scores with an increase in cecal butyrate levels. Probiotic treatment with a mixture of Lactobacillus and Clostridium butyricum did not show such an effect. Both antibiotic treatments significantly attenuated clinical and pathological scores. However, in contrast to GBF, this treatment led to a significant decrease in cecal butyrate levels. These data suggest that modification of the intestinal microflora by prebiotics, including GBF, may serve as a useful adjunct in the treatment of ulcerative colitis as well as antibiotic treatment.

Animal Feed↗
PubMed2002

Short-term oral administration of a product derived from a probiotic, Clostridium butyricum induced no pathological effects in rats.

Recent studies have suggested that short chain fatty acids (SCFAs) exert a therapeutic effect on some human and experimental animal diseases. In a previous study, we showed that Clostridium butyricum produces high levels of SCFAs in the culture system used. In addition, an additive based on yogurt was effective in eliminating and masking the odor derived from SCFAs in the product. The aim of the present study was to investigate the effects for oral administration of the product, which was derived from Clostridium butyricum and contains a high level of SCFAs, in rats. Male and female Wistar Hannover GALAS rats, 5 weeks old, were allowed a mixture of the standard diet plus the product derived from Clostridium butyricum (50% w/w) with 0.1% additive for 17 days (n=6). The control rats were also allowed a standard diet plus tap water (50% w/w) with 0.1% additive (n=6). After 17 days, a laparotomy was performed. A hemocyte count, and biochemical and electrolyte analyses were subsequently carried out. The esophagus, stomach, small intestine, cecum and large intestine were investigated macroscopically and microscopically. Results showed that the rats grew normally for the duration of the experimental period. In particular, the body weights of the product-fed male rats were significantly increased as compared to those of the control-fed male rats. There were no significant differences in the organic weight between the product-fed and control-fed rats, except for a significantly increased weight of the small intestine in the product-fed female rats. No pathological abnormalities were found in the hemocyte count, the biochemical and electrolyte analyses, or the macroscopic and microscopic findings. It is possible that this novel product with the additive exerts therapeutic effects on some gastrointestinal disorders.

Administration, Oral↗
PubMed2002

[Treatment of Crohn's disease by anti-cytokine monoclonal antibodies].

Pro-inflammatory cytokines such as TNF-alpha and IL-6 play a role in the pathogenesis of inflammatory bowel disease (IBD). Recent advances in the treatment with IBD patients, in particular Crohn's disease, are the use of anti-cytokine monoclonal antibodies against TNF-alpha. Three types of anti-human TNF-alpha antibodies have been developed. Infliximab is a chimeric antibody containing Fab portion of anti-human TNF-alpha mouse IgG and Fc portion of human IgG. CDP571 is a humanized (-95% human residues) monoclonal antibody, and is potentially less immunogenic than chimeric antibody. In this paper, we summarize the recent reports describing the clinical efficacy of these antibodies in the treatment of Crohn's disease.

Animals↗