Biomedical subjects

Yoshihide Fujiyama

Publications and source records attributed to Yoshihide Fujiyama.

At least 91 records · Page 5Linked to original sources

PubMed2003

Gastric inflammatory fibroid polyp treated with Helicobacter pylori eradication therapy.

Gastric inflammatory fibroid polyps (IFPs) are rare benign lesions that occur in the distal stomach. We describe a 70-year-old woman with Helicobacter pylon-positive gastric IFP treated with eradication. Gastroduodenal endoscopy revealed a pyramidal-shaped, broad-based tumor with an ulcerated apex at the antrum. Helicobacter pylori was positive by both histology and tissue culture, and eradication (a proton pump inhibitor, amoxicillin, and clarithromycin) was performed. After 3 months, the tumor morphologically changed and the apex ulcer was markedly enlarged. This case suggests that H. pylori may play a role in the pathophysiology of IFPs.

Aged↗

PubMed2003

Enteral and parenteral nutrition therapy for Crohn's disease.

Even with the development of new therapeutic agents, such as infliximab, enteral nutrition (EN) and parenteral nutrition (PN) therapies remain important for the treatment of Crohn's disease because Crohn's patients often require nutritional support. Furthermore, nutritional therapies can be used in the control of disease activity. Elemental diets, which are mainly used in EN therapy, consist of a refined amino acid mixture, glucose or maltodextrins and minimal essential fatty acids. EN therapy can reduce mucosal inflammation by the elimination of dietary antigens, which induce inflammation, and by reductions in fat, which activates inflammation. EN is applied not only as induction therapy, but also as maintenance therapy after remission (home EN). However, the unpalatability of elemental diets, difficulties related to self-intubation and the high cost of EN have limited its application as a primary therapy in western countries. PN is utilized as complete bowel rest supporting nutrition. However, since the therapeutic efficacies of EN and PN are similar, the indications for PN are limited and PN is mainly utilized in patients with bowel obstructions or severe fistulas. PN is also used as home therapy in the treatment of Crohn's patients with short bowel syndrome. However, long-term PN sometimes causes life-threatening complications including catheter-induced sepsis, liver failure and lethal mineral deficiencies. We suggest that gastroenterologists should recognize the advantages and limitations of all therapies and choose carefully or combine various therapies in order to maintain the quality of life in individual patients even if in cases where remission can not be achieved.

Animals↗

PubMed2003

Role of dietary fiber and short-chain fatty acids in the colon.

Luminal nutrition is important for maintenance of gastrointestinal mucosal structure and function. In particular, short chain fatty acids (SCFAs), metabolic products of anaerobic bacterial fermentation of dietary fiber and resistant starch, are particularly important as the preferred respiratory fuel of the colonocytes. A variety of biological effects of SCFAs have been reported, and there is now increasing number of experimental works showing new aspects of these molecules. For example, as the mechanisms mediating anti-inflammatory effects of SCFAs, several investigators identified the inhibitory effect of butyrate on proinflammatory cytokine-induced NF-kappaB activation. Various inflammatory responses are now discussed with the central role of NF-kappaB activation, and thus the inhibition of NF-kappaB activation represents the efficacy of dietary fiber and SCFAs in the treatment with inflammatory bowel disease. Furthermore, recent advance in molecular technology has identified mechanisms mediating anti-tumor effects of SCFAs. SCFAs modulate expression of cell cycle-regulating proteins and induce apoptosis in colon cancer cells. SCFAs increase the susceptibility of colon cancer cells to complement-mediated cell injury. In this review, new aspects of functions of SCFAs are focused and summarized.

Animals↗

PubMed2003

Mucosal permeability regulates receptor binding of luminal epidermal growth factor in the adult rat intestine.

Epidermal growth factor (EGF) stimulates repair in the damaged intestine, but its role in the normal intestine is not clear. Because EGF receptors are found on the basolateral surface but not the luminal surface, we hypothesized that mucosal permeability regulates EGF binding. Adult male rats were divided into 3 groups, one that was fed normal chow (the control), one that was starved for 4 days, and one that was given methotrexate (MTX) intragastrically (10 mg/kg/day for 3 days). The rats were sacrificed and everted sacks of the jejunum were made and incubated in EGF solution. Western blot analysis of mucosal homogenates showed that the amount of phosphotyrosyl EGF receptor in the starved and MTX-treated groups was, respectively, about 1.5 times and 2 times that in the control group. The mucosal permeability in the starved and MTX treated groups also increased and varied directly with the amount of phosphotyrosyl EGF receptor. These results suggest that in the adult rat intestine, luminal EGF may play a role only under tissue damage, where enhanced permeability permits the EGF to pass through the mucosa and bind to its receptor on the basolateral membrane.

Animals↗

PubMed2003

The free radical scavenger edaravone suppresses experimental closed duodenal loop-induced acute pancreatitis in rats.

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical acute pancreatitis. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental closed duodenal loop (CDL)-induced acute pancreatitis. In the CDL-pancreatitis model, after edaravone and vehicle saline were injected intravenously, pancreatitis was induced for 7 h by the CDL technique. The subsequent ascites volume, wet pancreatic weight, serum amylase levels, and pancreatic tissue lipid peroxide levels were evaluated. Pancreatic tissue damage was also evaluated histologically. In this CDL-induced pancreatitis model, edaravone treatment tended to reduce the ascites volume and inhibit the increases in the wet pancreatic weight. Edaravone also tended to reduced the microscopic mucosal damage scores and pancreatic tissue lipid peroxide levels. In particular, the serum amylase levels in the edaravone-treated rats (1-20 mg/kg i.v.) were significantly reduced as compared to the vehicle-treated rats. These results strongly support the involvement of ROS in the pathogenesis of CDL-induced acute pancreatitis and cytoprotective effects of free radical scavender against pancreatic acinar cells. A clinical effect for edaravone against acute pancreatitis is strongly expected.

Aldehydes↗

PubMed2003

The free radical scavenger edaravone suppresses experimental dextran sulfate sodium-induced colitis in rats.

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental dextran sulfate sodium (DSS)-induced colitis in rats. The rats were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. The edaravone and vehicle saline were injected subcutaneously twice a day. After the experimental period, the wet colonic weight, macroscopic mucosal damaged area, histological damage score, mucosal myeloperoxidase (MPO) activity, mucosal tissue lipid peroxidate and serum interleukin-6 (IL-6) levels were measured. In the DSS-induced colitis model, edaravone treatment (1-20 mg/kg day) significantly reduced the wet colonic weight, macroscopic damaged area, and the histological damage score. Edaravone treatment also reduced mucosal MPO activity, mucosal tissue lipid peroxidate level and serum IL-6 level. In particular, edaravone at a dose of 20 mg/kg day significantly reduced mucosal MPO activity and serum IL-6 level. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone against IBD patients is strongly expected.

Aldehydes↗

PubMed2003

The use of short-course zidovudine to prevent perinatal transmission of human immunodeficiency virus in rural Kenya.

To determine the feasibility of using short-course zidovudine (ZDV) to prevent mother-to-child transmission of human immunodeficiency virus (HIV) in a breastfeeding population in a rural area in Kenya, pregnant mothers attending clinics in seven health centers in western Kenya between 1996 and 1998 were requested to volunteer for participation in this study. The HIV-infected mothers were given a daily dose of 400 mg of ZDV starting at 36 weeks of gestation and another 300 mg every three hours intrapartum. After delivery, mothers and their children were followed-up and clinically monitored every 3-4 months for two years, and child and mother mortality rates were analyzed. Of the 825 mothers who consented, 216 (26.2%) were infected with HIV. Of those infected, 51 (23.6%) took the full prescribed dose, 69 (31.9%) took only the prenatal dose, and the remaining 96 (44.4%) did not take any dose. Failure to take ZDV was attributed mainly to delivery occurring earlier than expected, while non-compliance to the intrapartum dose was due to mothers giving birth at home and fear of traditional birth attendants. By the end of the second year, 75 HIV-exposed children (34.7%) and 33 HIV-infected mothers (15.3%) had died. The HIV-free survival of children at 24 months was significantly associated with mother survival (P < 0.001) and prenatal ZDV compliance (P < 0.003). Our findings suggest that implementation of programs for prevention of mother-to-child transmission of HIV in rural areas of Africa need to consider the various socioeconomic and cultural barriers that may prevent successful uptake of antiretroviral prophylaxes. Similarly, the rapid disease progression in mothers may eliminate the increase in child survival due to ZDV prophylaxis.

Adult↗

PubMed2003

The long-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 our 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 these SCFAs in the product. Recently, we reported that the oral administration of a high concentration (50% w/w) of this product derived from Clostridium butyricum for 17 days caused no pathological abnormalities in rats. The aim of the present study was to investigate the effects of the prolonged oral administration of this product in rats. Male and female Wistar Hannover GALAS rats, 5 weeks old, were given a mixture of a standard diet plus the product derived from Clostridium butyricum (5% w/w) with 0.1% additive for 16 months (n=6). The control rats were allowed the same standard diet plus tap water (5% w/w) with 0.1% additive (n=6). After 16 months, a laparotomy was performed. A hemocyte count, and biochemical and electrolyte analyses were subsequently carried out. The esophagus, stomach, small intestine, large intestine and pancreas were investigated macroscopically and microscopically. The results showed that the rats grew normally for the duration of the experimental period. The body weights of the product-fed rats were comparable with those of the control-fed rats. There were no significant differences in the organ weight between the product- and control-fed rats, except for a significantly increased weight of the large intestine in the product-fed male rats. No pathological abnormalities were found in the hemocyte count, the biochemical and electrolyte analyses, or the macroscopic and microscopic findings.

Administration, Oral↗

PubMed2003

Enteral alanyl-glutamine supplement promotes intestinal adaptation in rats.

Although parental administration of glutamine promotes intestinal adaptation, it is controversial whether enteral glutamine is effective after small bowel resection. To further evaluate the benefits of enteral supplementation, peptide and amino acid peptide transporter function must be considered. We evaluated the effect of enteral alanyl-glutamine based on the alteration of peptide and amino acid transporter expressions after massive small intestinal resection. Rats underwent 80% proximal intestinal resection. Expression of the glutaminase (GA), amino acid transporter B0 and peptide transporter PepT1 mRNA in the residual intestinal cells was initially examined by Northern blot analysis. Rats with a small bowel received a bolus supplement of glutamine (2.0 g/kg/day) + alanine (1.22 g/kg/day) mixture, alanyl-glutamine (2.972/kg/day) or saline for 3 days from one day before operation. On the 3rd postoperative day (POD) and the 7th POD, residual intestinal tissue was removed, and mucosal parameters were measured. The GA activity and GA mRNA significantly increased on the 1st POD. Although the levels of B0 mRNA gradually decreased, the PepT1 mRNA increased after surgery, and reached 150% of the initial level on the 5th POD. In the rats administered alanyl-glutamine, mucosal wet weight and protein content similarly increased with increasing villus height on the 7th POD. Enteral supplementation with alanyl-glutamine but not glutamine + alanine mixture promotes intestinal adaptation as evidenced by increased peptide transport after intestinal resection.

Alanine↗

PubMed2003

Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial.

Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Adult↗

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

In vivo cytokine responses in gut-associated lymphoid tissue (GALT) and spleen following oral administration of staphylococcal enterotoxin B.

The mechanisms responsible for oral tolerance have been analyzed using various antigens. The induction of oral nonresponsiveness to low doses of Staphylococcal Enterotoxin B (SEB), in which SEB-reactive clonal anergy and deletion are involved, has also been confirmed. However, few reports have examined the cytokine milieu of the mucosal and peripheral lymphoid tissue during tolerance induction after the oral administration of SEB. In this study, to elucidate the mechanism responsible for the oral tolerance to low dose of SEB, the cytokine responses of the gut-associated lymphoid tissues (GALT) and the spleen were examined using the reverse transcription-polymerase chain reaction (RT-PCR) method. After the oral administration of a single low dose of SEB, the expressions of Th2 and TGF-beta, and to a lesser extent Th1 mRNA were observed in the mucosa. In contrast, following repeated oral low doses of SEB, in a manner different from previous results using conventional antigens, no cytokine enhancements were demonstrated in the GALT or the spleen. In conclusion, the involvement of unknown inhibitory or regulatory cytokines, together with SEB-reactive clonal anergy and deletion, is suggested in the induction of oral tolerance to low dose SEB.

Animals↗

PubMed2002

Effect of a conserved mutation in uridine diphosphate glucuronosyltransferase 1A1 and 1A6 on glucuronidation of a metabolite of flutamide.

OBJECTIVE: We investigated how the conserved mutation (Y486D) changed the kinetic parameters of uridine diphosphate glucuronosyltransferase 1A1 and 1A6 (UGT1A1 and 1A6) for 2-amino-5-nitro-4-trifluoromethylphenol, which is a major metabolite of flutamide, a nonsteroidal antiandrogenic agent. METHODS: The wild-type or mutant cDNA-expressed UGT was co-incubated with 2-amino-5-nitro-4-trifluoromethylphenol (aglycone) and uridine diphosphate-glucuronic acid (UDP-GA, donor substrate). The glucuronidation of the aglycone was determined. RESULTS: The maximum velocities of the mutant UGT1A1 and UGT1A6 were about 12% and less than 1% of the corresponding wild-type, respectively. The Michaelis constant (K(M)) for the aglycone of the wild-type UGT1A1 was double that of the mutant, but the K(M) for UDP-GA of the wild-type UGT1A1 was not significantly different from that of the mutant. CONCLUSION: Patients with Y486D may accumulate excessive 2-amino-5-nitro-4-trifluoromethylphenol, which might lead to unexpected toxicity.

Androgen Antagonists↗

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↗