研究者詳細 - 仲瀬　裕志

論文 - 仲瀬　裕志

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Clinical challenges and images in GI. Meckel's diverticulum with an enterolith.

Norimitsu Uza, Hiroshi Nakase, Tsutomu Chiba

Gastroenterology 131 ( 2 ) 351, 690 2006年08月 [査読有り] [国際誌]

Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis.

Masanori Asada, Akiyoshi Nishio, Kazushige Uchida, Masahiro Kido, Satoru Ueno, Norimitsu Uza, Keiichi Kiriya, Satoko Inoue, Hiroshi Kitamura, Shinya Ohashi, Hiroyuki Tamaki, Toshiro Fukui, Minoru Matsuura, Kimio Kawasaki, Toshiki Nishi, Norihiko Watanabe, Hiroshi Nakase, Tsutomu Chiba, Kazuichi Okazaki

Pancreas ( LIPPINCOTT WILLIAMS & WILKINS ) 33 ( 1 ) 20 - 6 2006年07月 [査読有り] [国際誌]

OBJECTIVES: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. METHODS: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. RESULTS: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. CONCLUSIONS: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

DOI PubMed

Cytomegalovirus infection in patients with ulcerative colitis diagnosed by quantitative real-time PCR analysis.

Tadayuki Kou, Hiroshi Nakase, Hiroyuki Tamaki, Toyoichiro Kudo, Akiyoshi Nishio, Tsutomu Chiba

Digestive diseases and sciences ( SPRINGER ) 51 ( 6 ) 1052 - 5 2006年06月 [査読有り] [国際誌]

DOI PubMed

Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice

T Fukui, A Nishio, K Okazaki, N Uza, S Ueno, M Kido, S Inoue, H Kitamura, K Kiriya, S Ohashi, M Asada, H Tamaki, M Matsuura, K Kawasaki, K Suzuki, K Uchida, H Fukui, H Nakase, N Watanabe, T Chiba

GUT ( B M J PUBLISHING GROUP ) 55 ( 5 ) 607 - 615 2006年05月 [査読有り]

Background and aim: Major histocompatibility complex class II deficient (A alpha(o/o)) mice have decreased CD4(+) T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and A alpha(o/o) mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of A alpha(o/o) mice. Methods: Stomachs from 1-6 month old A alpha(o/o) mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist ( AG041R) was administered. Results: A alpha(o/o) mice had a diffusely thick corpus mucosa with infiltration of CD11b(+) granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1 beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-I alpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. Conclusion: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in A alpha(o/o) mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.

DOI PubMed

Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis.

Shinya Ohashi, Akiyoshi Nishio, Hajime Nakamura, Masahiro Kido, Satoru Ueno, Norimitsu Uza, Satoko Inoue, Hiroshi Kitamura, Keiichi Kiriya, Masanori Asada, Hiroyuki Tamaki, Minoru Matsuura, Kimio Kawasaki, Toshiro Fukui, Norihiko Watanabe, Hiroshi Nakase, Junji Yodoi, Kazuichi Okazaki, Tsutomu Chiba

American journal of physiology. Gastrointestinal and liver physiology ( AMER PHYSIOLOGICAL SOC ) 290 ( 4 ) G772-81 - G781 2006年04月 [査読有り] [国際誌]

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

DOI PubMed

Solitary rectal ulcer syndrome associated with ulcerative colitis.

Norimitsu Uza, Hiroshi Nakase, Kazuhiko Nishimura, Shunichi Yoshida, Kenji Kawabata, Tsutomu Chiba

Gastrointestinal endoscopy ( MOSBY-ELSEVIER ) 63 ( 2 ) 355 - 6 2006年02月 [査読有り] [国際誌]

DOI PubMed

Specific antibodies against recombinant protein of insertion element 900 of Mycobacterium avium subspecies paratuberculosis in Japanese patients with Crohn's disease.

Hiroshi Nakase, Akiyoshi Nishio, Hiroyuki Tamaki, Minoru Matsuura, Masanori Asada, Tsutomu Chiba, Kazuichi Okazaki

Inflammatory bowel diseases ( LIPPINCOTT WILLIAMS & WILKINS ) 12 ( 1 ) 62 - 9 2006年01月 [査読有り] [国際誌]

BACKGROUND: Mycobacterial avium subspecies paratuberculosis (MAP) infection has been hypothesized as an etiological factor of Crohn's disease (CD). However, the involvement of MAP in the pathophysiology of CD is controversial. The aim of this study is to investigate whether MAP is involved in the pathogenesis of CD with the glutathione S-transferase fusion recombinant protein encoding a portion of insertion element (IS) 900 (IS900-GST), which is specific for MAP. METHODS: Serum samples from the patients with CD (n = 50), ulcerative colitis (n = 40), colonic tuberculosis (n = 20), and non-IBD controls (n = 44), were applied for solid-phase enzyme-linked immunosorbent assay (ELISA) to detect antibodies against MAP and Saccharomyces cerevisiae. IS900-GST, which was made by the pGST-4T-2 vector inserted with polymerase chain reaction-amplified IS900DNA, was used as an antigen of MAP. Moreover, we studied the relationship between antibodies against IS900-GST and clinical characteristics. RESULTS: ELISA showed that the serum level of immunoglobulin G and immunoglobulin A antibodies against IS900-GST (anti-IS900) in patients with CD were significantly higher than those with ulcerative colitis, colonic tuberculosis, and control subjects. The levels of anti-IS900 tended to be higher in CD patients with small intestinal involvement than with colonic involvement alone. Anti-IS900 in patients with penetrating- and stricture-type CD was significantly higher than with inflammatory-type CD. Furthermore, a negative correlation was found between the titer of anti-IS900 and disease duration. Anti-IS900 was not associated with surgical treatment nor was it associated with the use of immunosuppressants. No significant correlation was observed between the serum levels of anti-IS900 and anti-S cerevisiae antibody. CONCLUSIONS: This is the first demonstration of the ELISA system of detecting antibodies against IS900 in IBD patients. MAP could be involved in the pathophysiology of Japanese patients with CD.

DOI PubMed

Diffuse hepatoid adenocarcinoma in the peritoneal cavity.

Hiroshi Kitamura, Kazuki Ikeda, Toyohiko Honda, Tetsuro Ogino, Hiroshi Nakase, Tsutomu Chiba

Internal medicine (Tokyo, Japan) ( JAPAN SOC INTERNAL MEDICINE ) 45 ( 19 ) 1087 - 91 2006年 [査読有り] [国内誌]

Hepatoid adenocarcinoma (HAC) is a rare tumor that occurs mostly in the gastrointestinal tract. We encountered a 68-year-old man suffering from HAC with severe ascites. The serum and ascitic alpha-fetoprotein (AFP) levels were markedly high. Computed tomography (CT) revealed that multiple nodular lesions were disseminated only in the peritoneal cavity. Based on laparoscopic and histological findings, this tumor was diagnosed as diffuse HAC which was developed primarily in the peritoneum. Despite treatments with appropriate chemotherapy, he died six months after diagnosis. According to literature updates, this is the first documented case of diffuse HAC which developed in the peritoneum.

DOI PubMed CiNii

A case of collagenous colitis (microscopic colitis) with a long time follow up

S. Mikami, H. Nakase, T. Sakuria, H. Sawami, T. Chiba

Gastroenterological Endoscopy 48 ( 11 ) 2645 - 2650 2006年 [査読有り]

DOI

Gluten sensitivity in Japanese patients with adult-onset cerebellar ataxia.

Masafumi Ihara, Fumi Makino, Hideyuki Sawada, Takahiro Mezaki, Kotaro Mizutani, Hiroshi Nakase, Makoto Matsui, Hidekazu Tomimoto, Shun Shimohama

Internal medicine (Tokyo, Japan) ( JAPAN SOC INTERNAL MEDICINE ) 45 ( 3 ) 135 - 40 2006年 [査読有り] [国内誌]

OBJECTIVE: Gluten sensitivity is associated with multiple neurological abnormalities including gluten ataxia, motor neuron disease-like neuropathy, small fiber type neuropathy, cognitive impairment, and even parkinsonism. We investigated whether or not gluten sensitivity is involved in Japanese patients with idiopathic cerebellar ataxia with extracerebellar presentation. PATIENTS OR MATERIALS: Fourteen patients with idiopathic cerebellar ataxia with extracerebellar presentation (autonomic instability, parkinsonism, or pyramidal dysfunction in varying combinations) were screened for anti-gliadin antibodies (AGA) to analyze for the presence or absence of gluten sensitivity. Patients with typical MR findings of multiple system atrophy of the cerebellar type were excluded. As disease controls without cerebellar ataxia, 9 patients with Parkinson's disease and 18 patients with amyotrophic lateral sclerosis were screened for AGA. Forty-seven normal controls were also screened for AGA. RESULTS: We found a high prevalence of AGA in 5 (36%) of 14 cerebellar ataxia patients, but in only 1 (4%) of 27 disease controls without cerebellar ataxia (odds ratio, 14.4; 95% CI, 1.41147; p<0.05) and in only 1 (2%) of 47 normal controls (odds ratio, 25.6; 95% CI, 2.66246; p<0.001). Among the cerebellar ataxia patients, atypical features such as sensorimotor neuropathy and/or mild cognitive impairment were more prevalent in the AGA-positive group (60%) than in the AGA-negative group (0%). In one of the ataxic patients with AGA, a gluten-free diet had positive effects on neurological symptoms and nutritional status. CONCLUSION: Gluten sensitivity is involved in at least some of the unexplained neurological symptoms of Japanese patients with adult-onset, sporadic cerebellar ataxia.

DOI PubMed CiNii

Rectal carcinoid tumor mimicking colonic adenomatous lesion.

Hiroshi Nakase, Minoru Matsuura, Norimitsu Uza, Satoru Ueno, Akiyoshi Nishio, Tsutomu Chiba

Gastrointestinal endoscopy ( MOSBY, INC ) 62 ( 6 ) 976 - 7 2005年12月 [査読有り] [国際誌]

DOI PubMed

IBD患者における骨減少と尿中Glaとの相関性

桑原晶子, 幣憲一郎, 姫野雅子, 辻秀美, 仲瀬裕志, 千葉勉, 田中清, 木戸詔子

日本病態栄養学会誌 ( (一社)日本病態栄養学会 ) 8 ( 4 ) 390 - 390 2005年11月

炎症性腸疾患(IBD)患者における骨減少及び脂溶性ビタミン欠乏症(第2報)

辻秀美, 幣憲一郎, 奥野梓, 土屋恵美, 姫野雅子, 桑原晶子, 仲瀬裕志, 千葉勉, 木戸詔子, 田中清

日本病態栄養学会誌 ( (一社)日本病態栄養学会 ) 8 ( 4 ) 390 - 390 2005年11月

Possible role of REG I alpha protein in ulcerative colitis and colitic cancer

A Sekikawa, H Fukui, S Fujii, A Nanakin, N Kanda, Y Uenoyama, T Sawabu, H Hisatsune, T Kusaka, S Ueno, H Nakase, H Seno, T Fujimori, T Chiba

GUT ( B M J PUBLISHING GROUP ) 54 ( 10 ) 1437 - 1444 2005年10月 [査読有り]

Background and aims: Although regenerating gene (REG) I alpha protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG I alpha gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG I alpha gene expression and whether REG I alpha protein has a trophic and/or an antiapoptotic effect on colon cancer cells. Methods: Expression of REG Ia mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG I alpha promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG I alpha protein on growth and H2O2 induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. Results: REG I alpha protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ia mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ia promoter activity was enhanced by stimulation with interferon gamma or interleukin 6. REG I alpha protein promoted cell growth and conferred resistance to H2O2 induced apoptosis in LoVo cells. REG I alpha protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. Conclusions: The REG I alpha gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.

DOI PubMed

Cecal ameboma.

Minoru Matsuura, Hiroshi Nakase, Takahiro Fujimori, Kazuo Mizuma, Yoshiyasu Tsuda, Tsutomu Chiba

Gastrointestinal endoscopy ( MOSBY, INC ) 62 ( 3 ) 442 - 3 2005年09月 [査読有り] [国際誌]

DOI PubMed

Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1.

Kimio Kawasaki, Akiyoshi Nishio, Hajime Nakamura, Kazushige Uchida, Toshiro Fukui, Masaya Ohana, Hazuki Yoshizawa, Shinya Ohashi, Hiroyuki Tamaki, Minoru Matsuura, Masanori Asada, Toshiki Nishi, Hiroshi Nakase, Shinya Toyokuni, Wenrui Liu, Junji Yodoi, Kazuichi Okazaki, Tsutomu Chiba

Laboratory investigation; a journal of technical methods and pathology ( NATURE PUBLISHING GROUP ) 85 ( 9 ) 1104 - 17 2005年09月 [査読有り] [国際誌]

Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive oxygen species and regulating redox-sensitive transcription factors. TRX-1 is induced in various inflammatory conditions and shows cytoprotective action. We investigated the roles of TRX-1 in the host defense mechanism against Helicobacter felis (H. felis) infection. Transgenic (TG) mice overexpressing human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2 months, histology, oxidative damage, and gene expression of several cytokines, including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the effects of TRX-1 on oxidative stress and neutrophil migration were studied both in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT mice developed moderate-to-severe gastritis, whereas the development of gastritis was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers, 8-hydroxy-2'-deoxyguanosine and malondialdehyde, increased in the stomach of infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1beta and tumor necrosis factor-alpha gene expression in H. felis-infected TRX-1-TG mice was significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.

DOI PubMed

Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapies

H Seno, H Nakase, T Chiba

ALIMENTARY PHARMACOLOGY & THERAPEUTICS ( BLACKWELL PUBLISHING ) 21 ( 2 ) 32 - 36 2005年06月 [査読有り]

Background: The treatment of functional dyspepsia is controversial. Aim: The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. Patients and methods: Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. Results: Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 +/- 0.14 to 1.57 +/- 0.2 0; in the famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride-and famotidine-treated patients (P < 0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary. visual analogue scale score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and at 2 weeks, respectively. without any significant improvement. Conclusions: A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients.

DOI PubMed

Usefulness of famotidine in functional dyspepsia patient treatment: Comparison among prokinetic, acid suppression and antianxiety therapies

H. Seno, H. Nakase, T. Chiba

Alimentary Pharmacology and Therapeutics, Supplement 21 ( 2 ) 32 - 36 2005年06月 [査読有り]

Background: The treatment of functional dyspepsia is controversial. Aim: The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. Patients and methods: Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. Results: Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 ± 0.14 to 1.57 ± 0.20 in the famotidine from 2.04 ± 0.16 to 1.09 ± 0.12 (mean ± S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride- and famotidine-treated patients (P < 0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary, visual analogue scale score in the tandospirone therapy was 2.23 ± 0.20 and 2.13 ± 0.22 before and at 2 weeks, respectively, without any significant improvement. Conclusions: A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients. © 2005 Blackwell Publishing Ltd.

PubMed

[Etiopathogenesis and aggravating factors in ulcerative colitis].

Satoko Inoue, Hiroshi Nakase, Tsutomu Chiba

Nihon rinsho. Japanese journal of clinical medicine 63 ( 5 ) 757 - 62 2005年05月 [査読有り] [国内誌]

Ulcerative colitis (UC) is a chronic inflammatory disease limited to the colon. Although the pathogenesis of inflammatory bowel disease (IBD) remains unclear, several studies have suggested that the onset and development of IBD require the interaction between genetic susceptibility, stimulation by luminal bacterial antigens and adjuvants, and episodic environmental triggers which break the mucosal barrier. There are many reports that experimental enterocolitis in animals does not occur in a sterile (germ free) environment and is prevented by antibiotics therapy. Moreover, patients with UC exhibit pathological immune responses to many commensal enteric bacterial species. Recent data showed that certain probiotic species decrease relapse of UC. These findings suggest that the most possible cause of UC is associated with chronic intestinal inflammation which is induced and perpetuated by non-pathogenic bacteria in genetically susceptible hosts.

PubMed

Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.

Minoru Matsuura, Kazuichi Okazaki, Akiyoshi Nishio, Hiroshi Nakase, Hiroyuki Tamaki, Kazushige Uchida, Toshiki Nishi, Masanori Asada, Kimio Kawasaki, Toshiro Fukui, Hazuki Yoshizawa, Shinya Ohashi, Satoko Inoue, Chiharu Kawanami, Hiroshi Hiai, Yasuhiko Tabata, Tsutomu Chiba

Gastroenterology ( W B SAUNDERS CO ) 128 ( 4 ) 975 - 86 2005年04月 [査読有り] [国際誌]

BACKGROUND & AIMS: Basic fibroblast growth factor (bFGF) is a promising therapeutic agent for various diseases. It remains unclear, however, whether bFGF is effective for the treatment of inflammatory bowel disease. The aim of this study was to examine the efficacy of bFGF on 2 experimental murine colitis models and to investigate its molecular mechanisms. METHODS: We evaluated the effects of human recombinant bFGF (hrbFGF) on mice with dextran sulfate sodium (DSS)-induced colitis and mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis as well as normal mice. Body weight, survival rate, and histologic findings of the colonic tissues were examined. Gene expression of tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, transforming growth factor (TGF)-beta, mucin 2 (MUC2), intestinal trefoil factor (ITF), and vascular endothelial growth factor (VEGF) in the colonic tissues was determined. The proliferation activity of hrbFGF on the colonic epithelium was evaluated by immunohistochemistry. RESULTS: Rectal administration of hrbFGF ameliorated DSS-induced colitis in a dose-dependent manner. Gene expression of TNF-alpha was significantly reduced in the colonic tissues of mice with DSS-induced colitis treated with hrbFGF, whereas MUC2 and ITF messenger RNA expression was up-regulated. Rectal administration of hrbFGF significantly improved the survival rate of mice with TNBS-induced colitis and partially ameliorated colitis. hrbFGF significantly increased the number of Ki-67-positive cells in the colonic epithelium of normal mice, and up-regulated the gene expression of COX-2, TGF-beta, MUC2, ITF, and VEGF in the colonic tissues. CONCLUSIONS: Rectal administration of bFGF might be a promising option for the treatment of inflammatory bowel disease.

DOI PubMed

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