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Biomedical subjects

Kazuma Fujimoto

Publications and source records attributed to Kazuma Fujimoto.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Barrett's esophagus and Helicobacter pylori].

Lifestyles of Japanese, including eating habits, have been similar to those in Western countries, which might be related to an increase in gastroesophageal reflux disease (GERD) in Japan. Barrett's esophagus is generally accepted as a complication of chronic and severe GERD. Helicobacter pylori (H. pylori) is a pathogen that is associated with atrophic gastritis, peptic ulcer disease, gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and so on. The relationship between H. pylori and GERD+ Barrett's esophagus is controversial. H. pylori eradication therapy may increase the risk for the development of GERD, which may lead to increase a risk factor of Barrett's esophagus and esophageal adenocarcinoma. This review gives the outline regarding GERD and the relation between Barrett's esophagus and H. pylori infection.

Adenocarcinoma↗
PubMed2004

Venous congestion induces mucosal apoptosis via tumor necrosis factor-alpha-mediated cell death in the rat small intestine.

BACKGROUND: Tissue and organic venous congestion is a common pathophysiologic phenomenon. However, it is unclear whether venous congestion induces small-intestinal mucosal apoptosis. The aim of this study was to investigate whether venous congestion, or congestion followed by re-outflow, induced small-intestinal mucosal apoptosis, and whether tumor necrosis factor-alpha is involved in this apoptosis. METHODS: Small-intestinal venous congestion was induced in rats by occlusion of the superior mesenteric vein with a micro-bulldog clamp. At the end of the congestive period, the clamp was released to facilitate congestion followed by re-outflow. The rats were injected with a neutral anti-tumor necrosis factor-alpha antibody (0.15 mg/kg) via the jugular vein for 30 min before venous congestion or congestion followed by re-outflow. Intestinal mucosal apoptosis was evaluated and tumor necrosis factor-alpha was assayed. The amounts of caspase-8, caspase-3, and cytochrome c were determined by Western blot analysis. RESULTS: Our results showed that venous congestion and congestion followed by re-outflow significantly increased mucosal apoptosis, the amount of mucosal tumor necrosis factor-alpha, and the levels of caspase-8 cleavage and caspase-3 activation, but did not induce cytochrome c release from mitochondria to the cytosol. Pretreatment with an anti-tumor necrosis factor-alpha antibody significantly reduced mucosal apoptosis after intestinal congestion or congestion followed by re-outflow. CONCLUSIONS: The present results support the view that venous congestion and congestion followed by re-outflow induce mucosal apoptosis in the rat small intestine, and show that the apoptosis occurs partly via tumor necrosis factor-alpha-mediated cell death.

Animals↗
PubMed2004

Interaction between morphology and angiogenesis in human early colorectal cancers.

Morphologically, early colorectal cancers are divided into two types: polypoid cancers and non-polypoid cancers. They vary in growth pattern, progression, and genetic alteration. Angiogenesis between polypoid and non-polypoid cancers may also be different. Therefore, the present study aims to evaluate angiogenesis in the early stages of colorectal malignancy, with particular attention to the morphological differences. The serial slides of all materials (48 polypoid cancers, 10 non-polypoid cancers, 20 adenomas and 10 normal tissues) were immunohistochemically stained for three endothelial cell markers (CD31, von Willebrand factor and CD105), counted for the number of microvessels in the same hot spots, and the angiogenic status was estimated. Polypoid cancers had higher microvessel counts and were more predominantly supplied by activated (CD105-positive, newly forming) microvessels than non-polypoid cancers. The present study indicated the possibility that the difference in growth pattern might be explained by the difference in angiogenesis between polypoid and non-polypoid cancers.

Adenocarcinoma↗
PubMed2004

Ischemic preconditioning attenuates ischemia-reperfusion-induced mucosal apoptosis by inhibiting the mitochondria-dependent pathway in rat small intestine.

Ischemic preconditioning provides a way of protecting organs from damage inflicted with prolonged ischemia-reperfusion. In this study, we investigated the mechanism of ischemic preconditioning involved in inhibition of prolonged ischemia-reperfusion-induced mucosal apoptosis in rat small intestine. Ischemic preconditioning was triggered by a transient occlusion of the superior mesenteric artery followed by reperfusion. Ischemia-reperfusion was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion in the small intestine. Ischemia-reperfusion alone induced mucosal apoptosis and mitochondrial respiratory dysfunction via promoted reactive oxygen species generation, reduced mitochondrial glutathione oxidation, increased mitochondrial lipid peroxidation, reduced mitochondrial membrane potential, and enhanced release of cytochrome c from mitochondria to activate caspase-9 and caspase-6 in the small intestine. Pretreatment with 20-min ischemia followed by 5-min reperfusion significantly inhibited the prolonged ischemia-reperfusion-induced mucosal apoptosis by 30%. Ischemic preconditioning ameliorated mitochondrial respiratory dysfunction by 50%, reduced reactive oxygen species generation by 38%, and suppressed mitochondrial lipid peroxidation by 36%, resulting in improvement of the mitochondrial membrane potential and prevention of cytochrome c release as well as caspase-6 activation. Results suggest that ischemic preconditioning attenuated ischemia-reperfusion-induced mucosal apoptosis partly by inhibiting the reactive oxygen species-mediated mitochondria-dependent pathway in the rat small intestine.

Animals↗
PubMed2004

Dietary corn oil promotes colon cancer by inhibiting mitochondria-dependent apoptosis in azoxymethane-treated rats.

How dietary corn oil is involved in colon carcinogenesis and cancer development is poorly understood. The aim of this study was to investigate whether long-term dietary corn oil promotes colon cancer by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were injected with AOM or with saline and fed on a basal diet or basal diet supplemented with 10% corn oil for 48 weeks. Colonic aberrant crypt foci (ACF) and tumors, including adenomas and carcinomas, were examined. Colonic apoptosis and cell proliferation were evaluated. Wild type (wt) p53 was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. In addition, Bcl-2, Bcl-xL, Bax, and Bak localized in the mitochondria were detected. Long-term dietary corn oil increased ACF in AOM-treated rats at 12 weeks and promoted colon cancer invasion at 48 weeks. Cancer invasion was not observed in the AOM-treated rats without dietary corn oil, although colon adenomas and cancers were detected. Apoptosis was decreased and cell proliferation was increased in the AOM-treated rats with dietary corn oil, compared with the AOM-treated rats with dietary basal diet. In these rats, mitochondrial wt p53 was significantly inhibited through decreased mitochondrial localization of wt p53 and increased cytosolic p53, resulting in the upregulation of Bcl-2 and Bcl-xL and the downregulation of Bak in the mitochondria. Results suggest that long-term dietary corn oil promotes AOM-induced colon cancer development partly by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis.

Animals↗
PubMed2003

The squamous cell carcinoma antigen 2 inhibits the cysteine proteinase activity of a major mite allergen, Der p 1.

The squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 belong to the ovalbumin-serpin family. Although SCCA1 and SCCA2 are closely homologous, these two molecules have distinct properties; SCCA1 inhibits cysteine proteinases such as cathepsin K, L, and S, whereas SCCA2 inhibits serine proteinases such as cathepsin G and human mast cell chymase. Although several intrinsic target proteinases for SCCA1 and SCCA2 have been found, the biological roles of SCCA1 and SCCA2 remain unknown. A mite allergen, Der p 1, is one of the most immunodominant allergens and also acts as a cysteine proteinase probably involved in the pathogenesis of allergic diseases. We have recently shown that both SCCA1 and SCCA2 are induced by two related Th2-type cytokines, IL-4 and IL-13, in bronchial epithelial cells and that SCCA expression is augmented in bronchial asthma patients. In this study, we explored the possibility that SCCA proteins target Der p 1, and it turned out that SCCA2, but not SCCA1, inhibited the catalytic activities of Der p 1. We furthermore analyzed the inhibitory mechanism of SCCA2 on Der p 1. SCCA2 contributed the suicide substrate-like mechanism without formation of a covalent complex, causing irreversible impairment of the catalytic activity of Der p 1, as SCCA1 does on papain. In addition, resistance to cleavage by Der p 1 also contributed to the inhibitory mechanism of SCCA2. These results suggest that SCCA2 acts as a cross-class serpin targeting an extrinsic cysteine proteinase derived from house dust mites and that it may have a protective role against biological reactions caused by mites.

Allergens↗
PubMed2003

Platelet-activating factor promotes mucosal apoptosis via FasL-mediating caspase-9 active pathway in rat small intestine after ischemia-reperfusion.

Platelet activating factor (PAF) is a proinflammatory lipid mediator for inflammatory response. It is unclear whether PAF is involved in the very complex process of ischemia-reperfusion (I/R) induced mucosal apoptosis in small intestine. Intestinal I/R was induced in rats intestine by 60 min occlusion of the superior mesenteric artery, followed by a 60 min reperfusion. I/R induced mucosal apoptosis and PAF activity but inhibited PAF-acetylhydrolase activity. Increases in interleukin-6 (IL-6) and decreases in IL-10 were observed. Western blot analysis showed that I/R induced expressions of platelet endothelial cell adhesion molecule-1 (PECAM-1) and Fas and Fas ligand (FasL) proteins, cleaved Bid, and enhanced the release of cytochrome c from mitochondria to activate caspase-9. Pretreatment of PAF antagonist BN-52021 attenuated these changes, except the increase in Fas. The results showed that I/R-inhibited mucosal PAF-acetylhydrolase activity resulted in an increase of activated PAF. The activated PAF increased the mucosal IL-6 and PECAM-1, enhanced the expression of FasL but not Fas, and led to the cleavage of Bid and the release of cytochrome c from mitochondria to activate caspase-9. This finding suggests that PAF promotes mucosal apoptosis after I/R in the rat small intestine partly through FasL mediating caspase-9 active pathway.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2003

Endoscopic injection sclerotherapy for esophageal varices in cirrhotic patients without hepatocellular carcinoma: a comparison of longterm survival between prophylactic therapy and emergency therapy.

BACKGROUND: This study aimed to determine whether prophylactic endoscopic injection sclerotherapy prolonged survival in patients with esophageal varices complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy. METHODS: The subjects included 160 patients suffering from esophageal varices complicated by liver cirrhosis without hepatocellular carcinoma. Sixty-eight patients underwent emergency therapy for bleeding varices and the remaining 92 patients underwent prophylactic sclerotherapy. All subjects continued to receive therapy until the varices disappeared. RESULTS: Five-year survival was significantly better in the prophylactic group compared with the emergency group. During the 5-year observation period, 20 of the 68 patients in the emergency group experienced rebleeding and 5 patients died as a result of rebleeding. These rates were significantly higher than those in the prophylactic group (1 of 9 patients with bleeding died among the 92 prophylactic sclerotherapy patients). Multivariate analysis showed that prophylactic therapy and Child's C hepatic function were significant factors for 5-year survival. CONCLUSIONS: Prophylactic sclerotherapy for esophageal varices might be more effective in prolonging longterm survival of patients complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy.

Adult↗
PubMed2003

Foveolar differentiation of mouse gastric mucosa in vitro.

We report a novel method that allows the culture of highly differentiated gastric surface mucous cells. Isolated mouse gastric epithelial cells and fibroblasts were co-cultured in a three-dimensional collagen gel system, and the reconstructed mucosal surface treated with an air-liquid interface. Cultured cells were examined by histology, immunohistochemistry, and electron microscopy. Isolated epithelial cells were positive for MUC5AC, and showed immature mucous cell features (pre-pit cell stage) on cell-free collagen gel. However, when given fibroblastic support, the epithelial cells differentiated into mature surface mucous cells (pit cell stage), and showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm. In the fine structure, the cells showed junctional complexes, basal lamina, and glycogen and secretary granules. Further treatment by the air-liquid interface environment modified the differentiated state of the pit cells (pit top cell stage); resulting in the expression of cathepsin E, the disappearance of glycogen granules and the apical accumulation of secretory granules along with an increase in apoptotic cells. This culture model should provide a useful tool for studying gastric epithelial cell biology and various diseases of the gastric mucosa.

Animals↗
PubMed2003

Endoscopic closure of perforations caused by EMR in the stomach by application of metallic clips.

BACKGROUND: The number of complications associated with use of EMR for early-stage gastric cancer, including perforation, has increased with the increasing use of this procedure. Endoscopic clip application was performed in patients who sustained a perforation as a result of EMR for gastric neoplasm. PATIENTS AND METHODS: Seven patients who underwent endoscopic application of metallic clips to close perforations were studied. The omental patch method was applied in one case with a large perforation. OBSERVATIONS: In all patients, endoscopic clip application successfully closed the perforation of the stomach, which occurred after EMR. No patient required laparotomy. CONCLUSIONS: The technique of endoscopic clip application might be useful for treatment of patients who sustain a perforation caused by EMR.

Aged↗
PubMed2003

Chronic exposure to subtoxic levels of peroxidized lipids suppresses mucosal cell turnover in rat small intestine and reversal by glutathione.

Oxidative challenge can compromise intestinal growth and death responses. This studyexamines the effect of chronic consumption of subtoxic levels of peroxidized lipids on intestinal redox balance and turnover and the effect of glutathione (GSH) supplementation. Male Sprague-Dawley rats were fed standard rat chow or 4% peroxidized menhaden oil chow (2-8 weeks). Intestinal GSH and glutathione disulfide (GSSG), GSH synthetic and redox enzymes as well as proliferative (ornithine decarboxylase, ODC) and apoptotic activities were evaluated. Chronic peroxide intake did not affect overall animal growth, but decreased intestinal GSH/GSSG ratio that directly correlated with decreased GSH and increased GSSG, and suppressed peak circadian ODC activities and post-prandial mucosal apoptosis. Supplementation with GSH restored the mucosal GSH/GSSG ratio and abrogated the peroxide-induced suppression of intestinal cell turnover. Collectively, the results show that chronic lipid peroxide consumption induces intestinal GSH redox imbalance that interferes with regulation of enterocyte death and proliferation in vivo. These disruptive effects of lipid peroxides were reversed by GSH supplementation in accordance with the normalization of tissue GSH/GSSG redox balance.

Animals↗
PubMed2003

Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult subjects.

This study aimed to evaluate the correlation between symptoms and endoscopic findings in reflux esophagitis. Subjects, 8031 persons without medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia, and acid regurgitation by associated medical staff before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and 2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis indicated that the symptom most related to esophagitis was heartburn (odds ratio: 2.46), although approximately 40% of subjects with grade C or D did not complain of heartburn. Regarding the other symptoms, less than 30% subjects with severe esophagitis complained of the symptoms and the odds ratio was approximately 1. These results indicate that endoscopic esophagitis was not equivalent to any reflux symptoms from which subjects suffered in their daily lives.

Adult↗
PubMed2003

Chronic lipid hydroperoxide stress suppresses mucosal proliferation in rat intestine: potentiation of ornithine decarboxylase activity by epidermal growth factor.

We recently demonstrated that chronic exposure of rat intestine to sublethal levels of peroxidized lipids suppresses ornithine decarboxylase (ODC) activity, consistent with attenuated intestinal proliferation. The current study was designed to better understand the influence of exogenous epidermal growth factor (EGF) on intestinal proliferation in normal intestine and intestine that was challenged by oxidative stress induced by dietary consumption of peroxidized lipids. Male Sprague-Dawley rats (250-300 g) were fed standard chow (control) or peroxidized lipid chow for 4 weeks. EGF was injected intraperitoneally at a dose of 40 microg/kg. Intestinal proliferation was evaluated by ODC activity in fed or fasted states and at specified times during the circadian phase. Chronic peroxide consumption significantly attenuated ODC activities in association with increased tissue peroxide content. The suppressed ODC activities were restored to control values by EGF in the small intestine; in the colon, EGF increased ODC activity threefold over control rats given EGF. This elevated colonic ODC activity was correlated with decreased tissue GSSG and an increased GSH/GSSG ratio. These results show that EGF administration reverses the suppression of intestinal ODC activities induced by chronic peroxidized lipid intake. In contrast, EGF significantly elevates proliferative activity in the peroxide-stressed colon. This exaggerated proliferation may contribute to a better understanding of colonic susceptibility to oxidant-induced malignant transformation.

Animals↗
PubMed2003

Endoscopic injection sclerotherapy for esophageal varices in cirrhotic patients with hepatocellular carcinoma: risk factors for survival.

GOALS: We previously showed that endoscopic injection sclerotherapy (EIS) prolonged survival in patients with esophageal varices complicated by hepatocellular carcinoma (HCC) and liver cirrhosis. Here, we evaluated risk factors that affect EIS outcomes. Among factors, the difference between prophylactic and emergency EIS was of interest, and we analyzed precisely. STUDY: Subjects were 134 patients with esophageal varices complicated by HCC and liver cirrhosis: 38 underwent emergent therapy for bleeding varices and 96 underwent prophylactic sclerotherapy. RESULTS: During 2-year observation, 22 of the 38 (57.9%) and 38 of the 96 (39.6%) died. Analysis by univariate Cox's proportional hazard model indicated that prognosis of patients receiving emergency EIS was inferior to those with prophylactic EIS. However, multivariate Cox's analysis showed that emergency EIS itself extended survivals of those with esophageal varices complicated by HCC and liver cirrhosis. Patients' hepatic function (Child-Pugh classes) and tumor sizes were also statistically significant factors for survival. Neither prophylactic nor emergency EIS prolonged survival of patients with Child C hepatic function or those with HCCs larger than 5 cm. CONCLUSIONS: The prophylactic sclerotherapy for esophageal varices prolongs long-term survival of patients with liver cirrhosis and HCC, better than emergency therapy. However, EIS itself had no beneficial effect on patients with poor disease status.

Esophageal and Gastric Varices↗
PubMed2003

Evaluation of endoscopic hemostasis with metallic hemoclips for bleeding gastric ulcer: comparison with endoscopic injection of absolute ethanol in a prospective, randomized study.

OBJECTIVE: Although metallic hemoclips have been used for hemostasis of bleeding ulcer, there have been few prospective trials to evaluate their efficacy. In this study, a prospective, randomized trial was performed to evaluate endoscopic hemoclipping for bleeding gastric ulcer in comparison with endoscopic injection of absolute ethanol. METHODS: During the period 1995-1998, 126 gastric ulcer patients with bleeding or nonbleeding visible vessel were considered for entry. They were randomly assigned to one of three groups: endoscopic hemostasis performed with injection of absolute ethanol (group I, n = 42), hemoclipping (group II, n = 42), and a combination of the two methods (group III, n = 42). RESULTS: The permanent hemostatic rate was 85.7% in group I, 90.5% in group II, and 92.9% in group III. The mean volume of blood transfusion was 313 +/- 77 ml in group I, 274 +/- 54 ml in group II, and 163 +/- 42 ml in group III, which was significantly less than in groups I or II (p < 0.05). No patients required emergency surgery. Five patients died within a month after initial hemostasis as a result of unrelated conditions. CONCLUSIONS: Endoscopic hemostasis with hemoclips for bleeding gastric ulcer was as effective and safe as that with injection of absolute ethanol, and a combination of ethanol injection and hemoclips did not result in a great advantage over the two individual procedures.

Equipment Design↗
PubMed2003

Intracerebroventricular administration of leptin-induced apoptosis in the rat small intestinal mucosa.

The localization of leptin and leptin receptors in the stomach and small intestine has been reported. Their function is still unknown, although leptin is a hormone that regulates appetite and fat-related metabolism. The small intestine is one of the important organs for regulating metabolism. The purpose of the present study was to investigate whether leptin regulates apoptosis in the small intestinal mucosa. Intestinal apoptosis was evaluated by percent fragmented DNA, electrophoresis, TUNEL staining, and western blotting analysis of caspase-3. Mucosal apoptosis in the rat jejunum and ileum was evaluated at 0, 3, 6, 12, and 24 hrs after injection. Rats were tested after ad libitum feeding and 24-hr fasting to exclude the anorectic effect of leptin. Leptin was injected intraperitoneally (ip) at a dose of 200 microg/rat and infused into the rat third cerebroventricle (icv) at a dose of 8 microg/rat. Leptin at a dose of 8 microg/rat significantly induced intestinal apoptosis in the small intestine at 3 and 6 hrs after icv administration in both ad libitum feeding and 24-hr fasted rats. This increase in apoptosis was not attenuated by vagotomy. Intestinal apoptosis increased 12 and 24 hrs after ip injection of leptin at a dose of 200 microg/rat. The peak of the increase in apoptosis in icv rats appeared earlier than that in ip rats. Leptin induced jejunal and ileal mucosal apoptosis in the rat, indicating that leptin might control intestinal function through the regulation of intestinal apoptosis.

Animals↗