Biomedical subjects

T Bamba

Publications and source records attributed to T Bamba.

At least 37 records · Page 2Linked to original sources

PubMed2001

Sequential changes in luminal microflora and mucosal cytokine expression during developing of colitis in HLA-B27/beta2-microglobulin transgenic rats.

BACKGROUND: Transgenic rats expressing HLA-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis resembling human inflammatory bowel disease. We investigated the sequential changes in the luminal bacterial flora and mucosal cytokine mRNA expression in this model. METHODS: HLA-B27 rats were maintained in a specific pathogen-free environment, and luminal microflora was evaluated by standard bacterial culture technique. The expression of mucosal cytokine mRNA was analysed by RT-PCR methods. RESULTS: Clinical symptoms of colitis appeared at 8 weeks of age. The total number of obligate anaerobes was higher than those of facultative anaerobes during the experimental period. At 6 weeks of age, the colonization of Bacteroides spp., Bifidobacterium spp. and Lactobacillus spp. was already detectable at high concentrations, whereas Clostridium spp. and Eubacterium spp. were not detected. The expression of proinflammatory cytokines (IL-Ibeta, IL-8 and TNF-alpha) appeared at 8 weeks of age, and these were detectable until 17 weeks. A similar pattern was observed in the expression of Th1 cytokines (IL-2, IL-12 and IFN-gamma). On the other hand, the expression of Th2 cytokines (IL-4, IL-10 and TGF-beta) was weak. IL-4 mRNA expression was weakly detectable only at 6 and 8 weeks of age. The expression of IL-10 and TGF-beta mRNA was scarcely detectable throughout the experimental period. CONCLUSION: The development of colitis may be mediated by both the predominant expression of Th1 cytokines and the weakness of Th2 cytokine expression in the mucosa. The colonization of anaerobic bacteria, especially Bacteroides spp., may be initiating and promoting these cytokine responses.

Animals↗

PubMed2001

Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines. IEC-6 and Caco-2 cells.

BACKGROUND: Bile acids have been shown to exhibit varying degrees of cytotoxicity, depending on their hydrophobic-hydrophilic balance. We have recently reported the strong cytotoxicity of hyodeoxycholic acid (HDCA), and the aim of the present study is to investigate the mechanisms underlying the cytotoxicity of HDCA. METHODS: The intestinal cell lines IEC-6 and Caco-2 cells were used. The cytotoxicities of various bile acids were evaluated using the MTS assay; their cytolytic effects were measured using the LDH release assay. The induction of apoptosis was determined by the specific figure changes in the cellular cytoplasm and nucleus, including DNA ladder formations. IL-8 synthesis induced by the bile acids was measured using an ELISA assay. RESULTS: The bile acids induced cytotoxic effects, LDH release, IL-8 synthesis and apoptosis, depending on their hydrophobic properties. On the other hand, HDCA induced strong cytotoxicity, apoptosis and IL-8 synthesis but not cytolysis, although HDCA has a hydrophilic nature. In addition, HDCA exerted the strongest effects on dispersing monolayer cells. CONCLUSIONS: These results strongly suggest that HDCA induces cytotoxicity through its ability to induce apoptosis rather than its detergent effect.

Apoptosis↗

PubMed2001

Effects of synthetic serine protease inhibitors on proliferation and collagen synthesis of human pancreatic periacinar fibroblast-like cells.

Protease inhibitors are currently used as therapeutic agents for chronic pancreatitis in Japan. We previously reported that human pancreatic periacinar fibroblast-like cells (hPFCs) could be cultured from isolated pancreatic acini, and those are thought to play a crucial role in pancreatic fibrosis correlating with platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGF-beta1) (Pancreas 1997;14: 373-82). The present study was designed to examine the effects of synthetic serine protease inhibitors (FOY-007 and FOY-305) on proliferation and collagen synthesis of hPFCs under cytokine stimulation. The cell proliferation and collagen synthesis were evaluated using assays of [3H]-thymidine incorporation and procollagen type I c-terminal peptide (PIP), and [14C]-proline incorporation to de novo synthesized collagen, respectively. The cell proliferation stimulated by PDGF was inhibited by the application of FOY-007 dose dependently (1-100 microM) and FOY-305 at 100 microM. FOY-007 attenuated the collagen synthesis and PIP production stimulated by TGF-beta1 dose dependently, but FOY-305 inhibited only PIP production. Both protease inhibitors demonstrated no effect on the proliferation and collagen synthesis of hPFCs when they were not stimulated by PDGF or TGF-beta1. Thus, serine protease inhibitors act on hPFCs to diminish the effects of PDGF on proliferation and the effects of TGF-beta1 on collagen synthesis.

Cell Division↗

PubMed2001

Alterations in intestinal microflora, faecal bile acids and short chain fatty acids in dextran sulphate sodium-induced experimental acute colitis in rats.

BACKGROUND: The physiological effects on faecal bile acids and short chain fatty acids (SCFAs) or intestinal microflora in dextran sulphate sodium (DSS)-induced colitis remain unknown and are an area of interest DESIGN ALTERATIONS: of these parameters in DSS-induced colitis in rats were evaluated. METHODS: Male Sprague-Dawley rats (n = 10) were given a 3% DSS aqueous solution orally for 7 days. The concentrations of bile acids and SCFAs in the faeces were measured using gas chromatography and high-performance liquid chromatography. Intestinal microflora, especially anaerobes, were investigated by microbiological methods. RESULTS: On day 7, the concentrations of lithocholic acid and alpha-muricholic acid were significantly decreased and that of cholic acid was significantly increased. There was a strong correlation between the concentration of cholic acid and the macroscopic area of damaged tissue in the colon (R = 0.74, P < 0.05). With respect to SCFAs, DSS administration significantly decreased the concentrations of acetic acid and n-butyric acid. There was also some correlation between the concentration of acetic acid and macroscopic damaged area in the colon (R = -0.60, P = 0.07). Bacteriological studies revealed significantly decreased eubacteria, bifidobacteria and total anaerobes after the administration of DSS. In contrast, lactobacilli were significantly increased. CONCLUSIONS: With the progression of DSS-induced colitis, faecal bile acids, SCFAs and intestinal microflora were altered. It is possible that these alterations contribute in part to the progression of DSS-induced colitis.

Acute Disease↗

PubMed2001

Epithelial expression of caveolin-2, but not caveolin-1, is enhanced in the inflamed mucosa of patients with ulcerative colitis.

Caveolae are vesicular invaginations of the plasma membrane that act as a scaffold of the assembly of many classes of signaling molecules. Caveolins are the principal structural component of caveolae membranes, and three distinct forms of caveolins have been identified: caveolin-1, caveolin-2, and caveolin-3. In this study, we evaluated the changes in the caveolin-1 and caveolin-2 expression in the inflamed mucosa of patients with IBD. Tissue samples were obtained endoscopically from patients with ulcerative colitis (UC) (n = 18), Crohn's disease (n = 10) and ischemic colitis (n = 8). Normal colorectal tissues were also obtained (n = 15). The caveolin expression was evaluated by standard immunohistochemical procedure. In normal colonic mucosa, caveolin-1 expression was detected in the smooth-muscle cells of the muscularis mucosae and the endothelial cells, but caveolin-2 expression was not detected. In the inflamed mucosa of patients with active UC, caveolin-2 expression was clearly detectable as small scattered foci on the luminal surfaces of epithelial cells, but caveolin-1 expression was similar to that in normal mucosa. Caveolin-2 expression increased in accordance with the disease activity of UC. This enhanced caveolin-2 expression was not detected in active Crohn's disease or ischemic colitis. In conclusion, we demonstrated that the epithelial expression of caveolin-2 is markedly enhanced in the inflamed mucosa of patients with UC. It is likely that the enhanced caveolin-2 expression in patients with UC was associated with the altered signal transductions in the intestinal epithelial cells. Furthermore, our results suggest that there are differences in the phenotypic features of epithelial cells between UC and Crohn's disease.

Caveolin 1↗

PubMed2001

Germinated barley foodstuff exhibits different adsorption properties for hydrophilic versus hydrophobic bile acids.

BACKGROUND/AIMS: Germinated barley foodstuff (GBF), a type of dietary fiber, exhibits therapeutic effects in ulcerative colitis (UC) patients. However, the precise mechanisms responsible for these effects are still under investigation. On the other hand, it has been suggested that bile salts in the gut lumen play an important role in the integrity of the intestinal mucosa. The aim of the present study was to investigate the ability of GBF to adsorb bile salts in vitro. METHODS: The binding capacities of GBF, enzymatically digested GBF (GBF-fiber), and alpha-cellulose for unconjugated and conjugated bile salts were measured using Langmuir's method. The morphology of these fibers was observed by light and fluorescence microscopy. RESULTS: GBF adsorbed bile salts very strongly, especially hydrophobic bile salts. Even after enzymatic digestion, the GBF fiber still exhibited strong binding capacity, whereas alpha-cellulose exhibited very low binding capacity. Microscopically, GBF consists mainly of aleurone, a lattice-like cell wall with cytoplasm enclosed. After enzymatic digestion, the cytoplasm was also digested. CONCLUSION: GBF possesses a great capacity to adsorb bile salts. This may be part of the mechanism for the therapeutic effects of GBF in UC patients.

Adsorption↗

PubMed2001

Role of complement activation and mast cell degranulation in the pathogenesis of rapid intestinal ischemia/reperfusion injury in rats.

The aim of this study is to define the putative role of complement activation and mucosal mast cell (MMC) degranulation in the pathogenesis of rapid ischemia-reperfusion (I/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complementary agent K-76COONa. To assess the role of MMC degranulation, we used the MMC stabilizer MAR-99 and genetically mast cell-deficient Ws/Ws rats. Autoperfused segments of the jejunum were exposed to 60 min of ischemia, followed by 60 min reperfusion. The epithelial permeability was assessed by (51)Cr-EDTA clearance rate, and the number of MMC was immunohistochemically assessed. I/R treatment induced a marked increase in mucosal permeability and MMC degranulation. The treatment with K-76COONa and MAR-99 significantly attenuated these changes. Furthermore, in Ws/Ws rats the increase in mucosal permeability and MMC degranulation was significantly attenuated. These findings indicate the role of complement activation and MMC activation in the pathogenesis of rapid intestinal I/R injury. A regulation of the complement activation and MMC degranulation may be one of the clinical strategies for prevention of I/R-induced mucosal injury.

Animals↗

PubMed2000

Sequential numerical changes of chromosomes 7 and 18 in diffuse-type stomach cancer cell lines: combined comparative genomic hybridization, fluorescence in situ hybridization, and ploidy analyses.

Sequential changes of chromosomal copy number were analyzed retrospectively in five diffuse-type gastric cancer cell lines by comparative genomic hybridization (CGH), DNA cytometry, and fluorescence in situ hybridization (FISH) with centromeric and painting probes. By CGH, we found loss of 18q21 in all of the cell lines and gains of 7p11-q31, 20q, and 22 in four of the five cell lines. Actual copy numbers of chromosomes 7 and 18 were determined by FISH: disomy 18 with (partial) loss of 18q in the two DNA-diploid cell lines (AGS and MKN-45), trisomy 7 in MKN-45, disomy 18 and tetrasomy 7 with one-copy loss of 7p and one-copy gain of 7q tip in DNA-triploid HSC-39/40A, and trisomy 18 and hexasomy 7 with one-copy loss of 7q in DNA-tetraploid KATO-III. Because the DNA aneuploidy is thought to result through tetraploidization, and the duplicated chromosomal changes in DNA aneuploid tumors seem to precede tetraploidization, the duplicated gain of chromosome 7 and one-copy loss of 7q in KATO-III were inferred to have occurred before and after tetraploidization, respectively. Similarly, HSC-39/40A were inferred to be preceded by the DNA-diploid stage with disomy 7 and monosomy 18. As the loss of 18q21 and the gain of 7p11-q31 were inferred to have occurred already in the DNA diploid stage in at least four and two of the cell lines, respectively, the 18q21 loss may be more important than the 7q gain as an earlier event in the genesis of diffuse-type stomach cancer. The combined CGH, FISH, and ploidy analyses thus give us a clue to extract important earlier events from the chromosomal changes that were screened by CGH alone.

Adenocarcinoma↗

PubMed2000

Enhancement of brush border membrane peptidase activity in rat jejunum induced by starvation.

Conflicting results have been obtained in previous studies concerning the adaptation of intestinal blush border membrane enzymes to starvation. This study was designed to clarity the changes in these enzymes under starvation conditions, using a molecular biological approach. Sprague-Dawley rats were starved or given total parenteral nutrition (TPN) for 5 days. Rats allowed free access to food were used as controls. Changes in the activity and expression of jejunal brush border membrane enzymes were compared between three groups. In the starved group, aminopeptidase N and dipeptidyl peptidase IV activity was significantly elevated to 177% and 166%, respectively, of control values. In contrast, sucrase and maltase activity was significantly decreased. The activity of these peptidases also tended to be increased at the renal brush border membrane. Up-regulation of peptidase activity was not evident in the TPN group. Western and Northern blot analysis revealed that the changes in aminopeptidase N activity were attributable to increases in the protein and mRNA level. The activity and expression of brush border membrane peptidases in rat jejunum is up-regulated during starvation, and these changes are considered to be an effect of whole-body malnourishment, rather than an absence of luminal nutrition.

Aminopeptidases↗

PubMed2000

Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease.

Elemental diet (ED) therapy has been established as primary therapy for Crohn's disease, and home enteral nutrition (HEN) has been reported to control relapse at a dose of more than 30kcal/kg of ideal body weight. However, a decrease in ED compliance with long-term use is becoming problem. We developed an n-3 fatty acid-rich diet and carried out nutritional education specifically for Crohn's disease patients using HEN to facilitate compliance and to improve their nutritional status. After the introduction of this n-3 rich diet, disease activity was not altered, and nutritional status, especially serum n-3 fatty acid levels, improved. The remission periods in patients with poor compliance seemed to be prolonged by the nutritional education. Thus, a n-3 rich diet in combination with nutritional education specific for Crohn's disease patients is very important for the in maintenance of high compliance and for maintaining nutritional balance.

Adolescent↗

PubMed2000

Effect of germinated barley foodstuff administration on mineral utilization in rodents.

Germinated barley foodstuff (GBF), which is derived from the aleurone and scutellum fractions of germinated barley, is rich in water-insoluble dietary fiber, which reportedly modulates mineral absorption in vivo. This study was conducted to examine whether GBF affects mineral absorption. We performed three experiments. In experiment 1, female ICR mice (4 weeks old) were fed a diet supplemented with 10% GBF or cellulose (CE; as a control) for 24 weeks. Body weight and food intake were recorded twice weekly. On the last experimental day, serum biochemical parameters, including electrolyte parameters, were determined, and major digestive organs were examined histopathologically. In experiment 2, male Sprague-Dawley rats (5 weeks old) were fed the CE and GBF diets, with the mineral content of the CE diet adjusted to the same level as that in the GBF diet, for 14 days, and the intake and fecal excretion of minerals (calcium, Ca; magnesium, Mg: Iron, Fe; Phosphate, P) were determined for the last 3 days. In experiment 3, the binding of Ca and Mg to GBF or cellulose and the release of Ca and Mg from GBF or cellulose was measured in phosphate buffer (pH 6.8). Long-term administration of GBF did not affect the growth rate of mice. GBF did not inhibit the absorption of Ca and Mg, and rather promoted the absorption of Ca and Mg by the gastrointestinal tract. The absorption of Fe and P was not attenuated by GBF administration, and GBF contained only a low level of phytic acid. GBF did not inhibit mineral absorption, differing from the effect of other dietary fibers, and is expected to be useful as a dietary source of Ca and Mg.

Absorption↗

PubMed2000

Efficacy of oral adsorbent for treatment of peristomal fistula associated with Crohn's disease.

Perianal fistulae are frequently seen complications in Crohn's disease. Although surgical procedures such as Seton's method have been devised, many patients still suffer from fistulae that are resistant to conventional therapy. We administered oral adsorbent to a patient with disease Crohn's who had a complicated peristomal fistula that did not improve with conventional therapy. Six grams of oral adsorbent (AST-120) were added daily to a regimen of elemental diet therapy and prednisolone. The fistula gradually decreased in size after the administration of the oral adsorbent, and had healed completely after 40 days' treatment. There were no side effects from the oral adsorbent. This case report suggests that oral adsorbent is an effective treatment for peristomal fistula associated with Crohn's disease.

Administration, Oral↗

PubMed2000

Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats.

Butyrate enemas have been reported to be effective in ulcerative colitis. However, long-term use is difficult because of the troublesome procedure and the unpleasant smell. We therefore investigated the effects of the oral administration of Clostridium butyricum M588 (CBM588), an enterobacterium producing butyrate, in dextran sodium sulfate (DSS)-induced colitis in rats. First, we confirmed the effects of pre-treatment with a butyrate enema on DSS colitis. We then studied the efficacy of oral administration of CBM588 which was started 1 week prior to the induction of DSS colitis. In the CBM588 group, the ulcer index and myeloperoxidase (MPO) activity in the distal colon were significantly lower than in the control group. Proliferating cell nuclear antigen (PCNA) immuno-positive cells were increased around the ulcer in the CBM588 group. In regard to the contents of the cecum and colon, the proportions of Lactobacillus and Eubacterium were increased in the cecum in the CBM588 group. Further, there were significant increases of n-butyrate, propionate, and acetate concentrations in the cecum in the CBM588 group. These results indicated that the oral administration of CBM588 alleviated DSS-induced colitis, and may be useful instead of butyrate enema.

Acetates↗

PubMed2000

Papillary serous carcinoma of the peritoneum: analysis of clonality of peritoneal tumors.

Papillary serous carcinoma of the peritoneum (PSCP) is a primary neoplasm of peritoneal origin, and is histologically difficult to differentiate from papillary serous carcinoma of the ovary (PSCO). PSCP is frequently accompanied by many peritoneal tumors, and has been managed as a disseminated disease. In previous reports, however, the clonality of the tumors has not been fully discussed. Recently, the significant roles of the p53 and BRCA1 genes in PSCP have been reported. In this study, we investigated immunohistochemical staining for p53 proteins, and investigated p53 gene mutations, using DNA sequencing analysis, to clarify the clonality of PSCP tumors. Immunohistochemically, all the tumor samples demonstrated nuclear overexpression of p53 proteins, and the DNA sequencing analysis of the p53 gene showed diverse point mutations at codons 167 and 192 in two of four anatomically different tumors. In conclusion, the possibility of polyclonality of PSCP tumors is suggested.

Aged↗

PubMed2000

Subacute hepatic failure associated with a new antidiabetic agent, troglitazone: a case report with autopsy examination.

An autopsy case of fatal subacute hepatic failure after administration of troglitazone is described. The liver dysfunction developed about five months after the patient, a sixty-three-year-old woman, had been initially treated with troglitazone. The patient developed hepatic failure and died despite various hepatic auxiliary treatments such as plasmapheresis. Autopsy findings revealed focal liver cell necrosis, cholestasis and steatosis with infiltration of lymphocytes and neutrophils and lack of regenerative activity. The causative mechanism of liver dysfunction may be metabolite aberration, as a result of accumulation of hepatotoxic metabolite(s), in a category of idiosyncratic liver injury. It is proposed to monitor liver function strictly and periodically for the diabetic patients prescribed troglitazone.

Chromans↗

PubMed2000

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen.

BACKGROUND: The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. AIMS: To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. METHODS: Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. RESULTS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. CONCLUSIONS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Acute Disease↗

PubMed2000

Adsorption and pharmacokinetics of cyclosporin A in relation to mode of infusion in bone marrow transplant patients.

Two main factors that affect the pharmacokinetics of cyclosporin A (CsA) during 24-h durable intravenous (DIV) administration have been reported, namely physiological changes after bone marrow transplantation, and blood sampling through indwelling lines. In addition, it has been found that infusion sets made of polyvinyl chloride (PVC) markedly adsorb CsA. We conducted in vitro adsorption studies of CsA on infusion sets, and the administration routes that are used in the treatment of patients with bone marrow transplantation. We also examined the effects of administration route on CsA pharmacokinetics in clinical practice. The in vitro adsorption study using 30-mm segments of lumen from commercially available infusion sets showed that the degree of CsA adsorption per area of lumen made of PVC was significantly higher than that in those made of polyethylene (PE) or polybutadiene (PB), which showed no adsorption of CsA. Due to its adsorption, use of infusion sets made of PVC resulted in about a 40-50% loss of CsA dose, which affected the pharmacokinetic parameters during 24-h DIV, while those made of PE and PB did not. The use of non-PVC infusion sets should allow for accurate monitoring of CsA results, and provide cost benefit in the treatment of bone marrow transplantation.

Adsorption↗

PubMed2000

Development of dextran sulphate sodium-induced experimental colitis is suppressed in genetically mast cell-deficient Ws/Ws rats.

Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC). In the present study we investigated the role of intestinal MMC in the development of dextran sulphate sodium (DSS)-induced experimental colitis using Ws/Ws rats. Ws/Ws and control (+/+) rats were given a 3% DSS aqueous solution orally for 10 days, and the subsequent mucosal damage was evaluated macroscopically and histologically. The mucosal myeloperoxidase (MPO) activities and histamine levels were also measured. (i) DSS induced severe oedema and hyperaemia with sporadic erosions in the control (+/+) rats, but these changes were significantly attenuated in the Ws/Ws rats (P < 0.01). (ii) The microscopic mucosal damage score was lower in the Ws/Ws rats than in the control (+/+) rats (P = 0.06). (iii) There were no significant differences in mucosal MPO activity between the Ws/Ws and control (+/+) rats (P = 0.46). (iv) The mucosal histamine levels in the colon were significantly reduced in the Ws/Ws rats compared with the control (+/+) rats (P < 0.05). (v) Significant positive correlations were observed between mucosal histamine levels and the degree of mucosal oedema (calculated as colonic wet weight/protein content) (r = 0.778, P < 0.01), and between histamine levels and the macroscopic damage (r = 0.623, P < 0.05), respectively. (vi) DSS induced a local recruitment of MMC in the colonic mucosa of Ws/Ws rats, and mucosal damage gradually increased in accordance with this MMC recruitment. These results indicate that MMC play an important role in the development of DSS colitis.

Animals↗