研究者詳細 - 仲瀬　裕志

論文 - 仲瀬　裕志

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Refractory enterovesical and duodenocolic fistulas in Crohn's disease successfully managed with tacrolimus.

Akihisa Fukuda, Hiroshi Nakase, Hiroshi Seno, Motoshige Nabeshima, Mitsutaka Sawada, Tsutomu Chiba

Journal of gastroenterology ( SPRINGER TOKYO ) 40 ( 4 ) 433 - 5 2005年04月 [査読有り] [国内誌]

A case of autoimmune pancreatitis associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

Toshiro Fukui, Kazuichi Okazaki, Hazuki Yoshizawa, Shinya Ohashi, Hiroyuki Tamaki, Kimio Kawasaki, Minoru Matsuura, Masanori Asada, Hiroshi Nakase, Yasuaki Nakashima, Akiyoshi Nishio, Tsutomu Chiba

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] ( KARGER ) 5 ( 1 ) 86 - 91 2005年 [査読有り] [国際誌]

We report a very rare case of autoimmune pancreatitis (AIP) associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome. The patient had an enlarged pancreas, and autoantibodies were detected in the serum. Serum IgG and IgG4 concentrations were also elevated. Endoscopic retrograde cholangiopancreatography revealed an irregular narrowing of the main pancreatic duct from the head to the body and sclerotic change in the intrapancreatic common bile duct, which later extended to the intrahepatic bile ducts. In addition, histological examination of the liver revealed lymphocytic sclerosis around the bile ducts, similar to the histology in the pancreas of AIP. Retroperitoneal tumors were diagnosed as retroperitoneal fibrosis by histological examination. Serological and functional abnormalities suggestive of Sjögren's syndrome were detected, and histological findings of the lip were compatible with Sjögren's syndrome. Immunohistochemistry of each lesion disclosed that most of the infiltrating lymphocytes were T cells with similar levels of both CD4+ and CD8+ cells. Moreover, some of the infiltrating plasma cells were positive for anti-IgG4 monoclonal antibody. These diseases were dramatically improved by steroid therapy. Although the pathophysiology of AIP is still unclear, the present case suggests a common pathophysiological mechanism for AIP, sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

DOI PubMed

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

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

Am J Physiol Gastrointest Liver Physiol. Dec 1, 2005. 2005年 [査読有り]

Metastatic thyroid lymphoma.

Masanobu Katayama, Hiroshi Nakase, Kenji Kanaji, Tadashi Matsumura, Tsutomu Chiba, Akira Tanaka

Gastrointestinal endoscopy ( MOSBY, INC ) 60 ( 4 ) 605 - 6 2004年10月 [査読有り] [国際誌]

DOI PubMed

実験的急性膵炎モデルにおけるチオレドキシンの防御作用についての検討

大橋真也, 西尾彰功, 井上聡子, 北村浩, 桐谷景一, 吉澤はづき, 浅田全範, 玉置敬之, 松浦稔, 川崎公男, 福井寿朗, 仲瀬裕志, 中村肇, 千葉勉

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 101 ( 臨増大会 ) A856 - A856 2004年09月

Characteristics of gastric B-cell lymphoma of mucosa-associated lymphoid tissue type involving multiple organs.

Masahiro Iwano, Kazuichi Okazaki, Kazushige Uchida, Hiroshi Nakase, Masaya Ohana, Yumi Matsushima, Hiroshi Inagaki, Tsutomu Chiba

Journal of gastroenterology ( SPRINGER TOKYO ) 39 ( 8 ) 739 - 46 2004年08月 [査読有り] [国内誌]

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma involving multiple organs is not well characterized. METHODS: To obtain a better understanding of gastric MALT lymphoma with multiple organ involvement, we compared Helicobacter pylori infection status; response to eradication therapy; prevalence of genetic abnormality, including t(11;18)(q21;q21); and clonality of tumor cells between patients with gastric MALT lymphoma with and without multiple organ involvement. RESULTS: Of 54 patients with only gastric involvement, 51 were positive for H. pylori (94.4%), whereas only 3 of 9 patients with multiple organ involvement had the infection (33.3%). Among those who received eradication therapy, the remission rate in patients with only gastric involvement was significantly higher than that in patients with multiple organ involvement (71.4% vs 33.3%; P < 0.05). The positive rate of API2-MALT1 fusion transcripts was significantly greater in patients with multiple lesions with either single or multiple organ involvement than in those with a single gastric lesion (71.4% vs 12.5%; P < 0.05), but 2 of 2 patients with multiple gastric lesions had the fusion transcripts. Of 5 patients with multiple organ involvement tested for clonality of the CDR3 region, distinct clones were detected in lymphoma lesions in different organs in 3 patients, whereas the identical clone was present in the different lesions in the remaining 2 patients. CONCLUSIONS: Gastric MALT lymphoma with multiple organ involvement is often associated with API2-MALT1 fusion transcripts. Moreover, H. pylori infection is rare in patients with multiple organ involvement as compared to those with only gastric involvement. Patients with gastric MALT lymphoma with multiple organ involvement who are positive for H. pylori are resistant to eradication therapy.

DOI PubMed CiNii

Environmental pollutant tributyltin promotes Th2 polarization and exacerbates airway inflammation.

Takuma Kato, Ryuichi Uchikawa, Minoru Yamada, Naoki Arizono, Saeko Oikawa, Shosuke Kawanishi, Akiyoshi Nishio, Hiroshi Nakase, Kagemasa Kuribayashi

European journal of immunology ( WILEY-V C H VERLAG GMBH ) 34 ( 5 ) 1312 - 21 2004年05月 [査読有り] [国際誌]

It has been shown that a relatively high dose of tributyltin (TBT), which is recognized as a particularly notable environmental pollutant, exerts immunotoxic effects such as thymic atrophy via induction of T cell apoptosis. However, the effect of low doses of TBT on the immune responses remains unknown. Here we show that environmentally relevant doses of TBT promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4(+) T cells primed with anti-CD3 and splenic antigen-presenting cells (APC). TBT-induced Th2 polarization was indirect, working through APC via suppression of IL-12 production by macrophages/DC and the augmentation of IL-10 production by B cells. Th2 polarization was also induced in mice treated with TBT and immunized with OVA or infected with Nippostrongylus brasiliensis. Furthermore, airway inflammation in mice sensitized and challenged with OVA was exacerbated by the administration of TBT with concomitant augmentation of Th2-type immunity. Our results highlight the fact that an important environmental pollutant TBT may present significant risk for the induction of allergic diseases via promotion of Th2 polarization.

DOI PubMed J-GLOBAL

Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis

M Ohana, K Okazaki, C Oshima, K Kawasaki, T Fukui, H Tamaki, M Matsuura, M Asada, T Nishi, K Uchida, S Uose, H Nakase, M Iwano, Y Matsushima, H Hiai, T Chiba

GUT ( BRITISH MED JOURNAL PUBL GROUP ) 52 ( 8 ) 1102 - 1110 2003年08月 [査読有り]

Background and aim: Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice. Materials and methods: BALB/ c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated. Results: Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor β (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction. Conclusions: H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.

DOI PubMed

Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid follicles in Helicobacter pylori-infected neonatally thymectomized BALB/c mice.

Toshiki Nishi, Kazuichi Okazaki, Kimio Kawasaki, Toshiro Fukui, Hiroyuki Tamaki, Minoru Matsuura, Masanori Asada, Tomohiro Watanabe, Kazushige Uchida, Norihiko Watanabe, Hiroshi Nakase, Masaya Ohana, Hiroshi Hiai, Tsutomu Chiba

Infection and immunity ( AMER SOC MICROBIOLOGY ) 71 ( 4 ) 2153 - 62 2003年04月 [査読有り] [国際誌]

We previously described an animal model of Helicobacter pylori-induced follicular gastritis in neonatally thymectomized (nTx) mice. However, it is still not clear whether antigen-presenting dendritic cells (DCs) in the stomach have a role in the development of secondary follicles in H. pylori-infected nTx mice. We investigated the distribution of DC subsets using this model and examined their roles. To identify lymphoid and myeloid DCs, sections were stained with anti-CD11c (pan-DC marker) in combination with anti-CD8alpha (lymphoid DC marker) or anti-CD11b (myeloid DC marker) and were examined with a confocal microscope. Expression of macrophage inflammatory protein 3alpha (MIP-3alpha), which chemoattracts immature DCs, was analyzed by real-time PCR and immunohistochemistry. Follicular dendritic cells (FDCs) were stained with anti-SKY28 antibodies. In noninfected nTx mice, a few myeloid and lymphoid DCs were observed in the bottom portion of the lamina propria, whereas in H. pylori-infected nTx mice, there was an increased influx of myeloid DCs throughout the lamina propria. FDC staining was also observed in the stomachs of members of the infected group. MIP-3alpha gene expression was upregulated in the infected nTx group, and the immunohistochemistry analysis revealed MIP-3alpha-positive epithelial cells. These data suggest that H. pylori infection upregulates MIP-3alpha gene expression in gastric epithelial cells and induces an influx of myeloid DCs in the lamina propria of the gastric mucosa in nTx mice. Myeloid DCs and FDCs might contribute to the development of gastric secondary lymphoid follicles in H. pylori-infected nTx mice.

DOI PubMed

Biodegradable microspheres targeting mucosal immune-regulating cells: new approach for treatment of inflammatory bowel disease.

Hiroshi Nakase, Kazuichi Okazaki, Yasuhiko Tabata, Tsutomu Chiba

Journal of gastroenterology ( SPRINGER-VERLAG TOKYO ) 38 Suppl 15 59 - 62 2003年03月 [査読有り] [国内誌]

Several studies have indicated that active monocytes, such as macrophages and T cells, play an important role in the pathogenesis of chronic human inflammatory bowel disease (IBD), although the etiology remains unclear. Manipulation of these cells appears essential for the treatment of patients with IBD. Recently, considerable attention has been paid to the use of polymer microspheres for the sustained release of various drugs and the targeting of therapeutic agents to their site of action. It was reported that biodegradable poly-D,L-lactic acid (PDLLA) microspheres can be efficiently taken up by macrophages and M cells. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with PDLLA microspheres and gelatin microspheres (GM) on colitis models. In the first experiment, colitis was induced in Balb/c mice by 5% dextran sodium sulfate, and microspheres containing dexamethsone (Decadrone, Dx; Dx microspheres) were orally administered to these mice. Serum levels of Dx did not reach a detectable level after administration of Dx microspheres. The tissue distribution of microspheres containing 125I-Dx in inflamed colon was significantly higher than that in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of mice treated with Dx microspheres were significantly lower than in those treated with Dx alone. Gene expression of proinflammatory cytokines was remarkably downregulated in mice treated with Dx microspheres compared to Dx alone. Next, we investigated the effect of elimination of resident macrophages using microspheres containing dichloromethylene diphosphonate (DMDP) on IL-10 knockout mice. We administered DMDP microspheres to IL-10 KO mice rectally and assessed whether this reagent could reduce the number of local Mac-1-positive cells in the intestine and suppress the development of colitis in IL-10 KO mice. DMDP microspheres reduced the numbers of resident macrophages in the colon of IL-10 KO mice but did not reduce the percentage of Mac-1-positive cells in the spleen, peritoneal cavity, or mesenteric lymph nodes. Depletion of intestinal macrophages significantly suppressed development of chronic colitis in IL-10 KO mice, however. Third, we developed gelatin microspheres containing IL-10, which can be released sustainedly to a local site without losing bioactivity. We administered these microspheres to IL-10 KO mice rectally to investigate whether this treatment can ameliorate colitis. Colonic inflammation in mice treated with GM-IL-10 is remarkably reduced compared to those treated with IL-10 alone. Moreover, expression of CD 40 on Mac-1-positive cells treated with GM-IL-10 is decreased more notably than in mice treated with IL-10 alone. These data suggest that a drug delivery system using these microspheres containing immunomodulatory agents may be a therapeutic approach to human IBD.

PubMed

Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice.

Norihiko Watanabe, Koichi Ikuta, Kazuichi Okazaki, Hiroshi Nakase, Yasuhiko Tabata, Minoru Matsuura, Hiroyuki Tamaki, Chiharu Kawanami, Tasuku Honjo, Tsutomu Chiba

Digestive diseases and sciences ( KLUWER ACADEMIC/PLENUM PUBL ) 48 ( 2 ) 408 - 14 2003年02月 [査読有り] [国際誌]

Uncontrolled activation of T cells and macrophages is involved in the development of inflammatory bowel disease (IBD). However, the precise role of intestinal macrophages for development of IBD is till unclear. To investigate the role of local macrophages for development of IBD, we developed poly-D, L-lactic acid microspheres containing dichloromethylene diphosphonate, which was specifically taken up by macrophages and depleted them, and then the animal model for human IBD was treated with this reagent. We have shown that rectal administration of the microspheres reduced the numbers of resident macrophages in the intestinal lymphoid follicles of interleukin-10-deficient mice. Importantly, depletion of intestinal macrophages was associated with suppression of development of chronic colitis. These results suggest that local macrophages in the intestine play a critical role in the development of chronic colitis in an animal model for IBD. Our study implies that elimination of resident macrophages in the intestine may become a therapeutic approach to IBD.

DOI PubMed

Hepatobiliary and pancreatic: Primary rabdomyosarcoma of the liver

H Nakase, K Okazaki, M Matsuura, T Chiba

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY ( WILEY-BLACKWELL ) 18 ( 1 ) 105 - 105 2003年01月 [査読有り]

DOI

Comparison of histological analysis and endosonographic features in esophageal granular cell tumors

Shujiro Yazumi, Rei Takahashi, Toru Kajiyama, Hiroshi Nakase, Norihiko Watanabe, Masaya Ohana, Shigemi Matsumoto, Hiroshi Seno, Mitsutaka Sawada, Kazushige Uchida, Motoshige Nabeshima, Kazuichi Okazaki, Tsutomu Chiba

Digestive Endoscopy 15 ( 4 ) 284 - 288 2003年 [査読有り]

Background: The increased use of esophagogastroduodenoscopy has revealed the esophagus to be a common site of occurrence of granular cell tumors (GCT). To clarify the endosonographic features of esophageal GCT, we compared endosonographic findings and histopathological analysis of resected specimens of esophageal GCT and submucosal leiomyomas. Methods: We enrolled a total number of 18 consecutive patients with esophageal submucosal tumors. They were preoperatively examined using 15 MHz or 20 MHz probe endoscopic ultrasonography. The endosonographic findings were retrospectively compared with hisopathological findings of the resected specimens. Results: Five GCT and 13 submucosal leiomyomas were diagnosed histologically as well as endosonographically. Pathological analysis revealed that the dispropotional mixture of tumor cells, fibrosis and muscularis mucosa within the GCT would be endosonographically visualized as a heterogeneous hypoechoic mass. Moreover, the laterally scattered tumor cells, together with adjacent thickened muscularis mucosa, are reflected by the unclear margin of the tumor by endoscopic ultrasonography. In contrast, in the submucosal leiomyomas, tumor cells and fibrosis were uniformly mixed and the margin of the tumor was clearly demarcated. These histological findings would be endosonographically recognized as a homogeneously hypoechoic mass with a clearly demarcated border. Conclusion: A high-frequency probe endoscopic ultrasonography is useful for differentiating esophageal GCT from submucosal leiomyomas. Considering the histological characteristics, esophageal GCT should be resected with adequate tumor-free margin when endoscopic treatment is applied.

DOI CiNii J-GLOBAL

Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis.

Kazuichi Okazaki, Hiroshi Nakase, Norihiko Watanabe, Yasuhiko Tabata, Yoshito Ikada, Tsutomu Chiba

Journal of gastroenterology ( SPRINGER-VERLAG TOKYO ) 37 Suppl 14 ( SUPPL. 14 ) 44 - 52 2002年11月 [査読有り] [国内誌]

We developed two kinds of delivery systems targeting mucosal immune regulating cells with poly (D,L-lactic acid) microspheres containing dexamethasone and dichloromethylene diphosphonate, and gelatine microspheres containing interleukin-10. To estimate the efficacy of these drug delivery systems, we studied the effects on experimental colitis induced by dextran sodium sulfate, 2,4,6-trinitrobenzene sulfonic acid, and interleukin-10-deficient mice. Intestinal administration of these microspheres significantly improved colitis with decreased histological score, myeloperoxidase activity, and nitric oxide production compared with mice treated with free agents. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in treated animals. Serum Dx, IL-10 levels, and systemic macrophages were unchanged after treatment. Our findings suggest that local macrophages in the intestine play a critical role in the initiation of chronic colitis in the animal model of inflammatory bowel disease (IBD). Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells may become a therapeutic approach to human IBD.

PubMed CiNii

A novel human fibroblast growth factor treats experimental intestinal inflammation.

Michael Jeffers, William F McDonald, Rajeev A Chillakuru, Meijia Yang, Hiroshi Nakase, Lisa L Deegler, Elizabeth D Sylander, Beth Rittman, Alison Bendele, R Balfour Sartor, Henri S Lichenstein

Gastroenterology ( W B SAUNDERS CO ) 123 ( 4 ) 1151 - 62 2002年10月 [査読有り] [国際誌]

BACKGROUND & AIMS: We recently identified a novel member of the human fibroblast growth factor (FGF) family of signaling molecules, designated FGF-20. In the present study, we examined the activity of this protein in 2 animal models of acute intestinal inflammation and in mechanistic studies in vitro. METHODS: In vivo experiments consisted of a murine dextran sulfate sodium (DSS) model of colitis and a rat indomethacin model of small intestinal ulceration/inflammation. Cell growth, restitution, gene expression (cyclooxygenase-2 [COX-2] and intestinal trefoil factor [ITF]), and prostaglandin E2 (PGE2) levels were examined in vitro. RESULTS: In the DSS-colitis model, prophylactic administration of FGF-20 significantly reduced the severity and extent of mucosal damage as indicated by a 55%-93% reduction in luminal blood loss, distal colonic edema, histologic inflammation, and epithelial cell loss relative to animals administered vehicle control. No toxicity was noted during administration of FGF-20 to normal controls. In addition, therapeutic administration of FGF-20 enhanced survival in this model. In the indomethacin-small bowel ulceration/inflammation model, administration of FGF-20 reduced small intestinal weight gain, necrosis, inflammation, and weight loss (36%-53% relative to vehicle control). In vitro studies demonstrated that FGF-20 stimulates growth, restitution, mRNA expression of COX-2 and ITF, and PGE2 levels in human intestinal epithelial cells and enhances the growth of human intestinal fibroblasts. CONCLUSIONS: FGF-20, having demonstrated therapeutic activity in 2 experimental models of intestinal inflammation, represents a promising new candidate for the treatment of human inflammatory bowel disease.

DOI PubMed

The "scarf-ring sign" of ball valve syndrome.

Shujiro Yazumi, Hiroshi Nakase, Yumi Matsushima, Tsutomu Chiba, Isao Shirahase, Shinsuke Yoshizaki, Shinitchi Mise

Gastrointestinal endoscopy ( MOSBY, INC ) 55 ( 4 ) 560 - 560 2002年04月 [査読有り] [国際誌]

DOI PubMed

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H-pylori-negative patients

H Nakase, K Okazaki, M Ohana, K Ikeda, K Uchida, S Uose, T Itoh, M Iwano, N Watanabe, S Yazumi, C Kawanami, F Inoue, T Chiba

ENDOSCOPY ( GEORG THIEME VERLAG KG ) 34 ( 4 ) 343 - 346 2002年04月 [査読有り]

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.

DOI PubMed

Experimental immune-mediated pancreatitis in neonatally thymectomized mice immunized with carbonic anhydrase II and lactoferrin.

Kazushige Uchida, Kazuichi Okazaki, Toshiki Nishi, Suguru Uose, Hiroshi Nakase, Masaya Ohana, Yumi Matsushima, Katsuyuki Omori, Tsutomu Chiba

Laboratory investigation; a journal of technical methods and pathology ( LIPPINCOTT WILLIAMS & WILKINS ) 82 ( 4 ) 411 - 24 2002年04月 [査読有り] [国際誌]

We previously reported that autoantibodies against carbonic anhydrase II and lactoferrin are frequently identified in patients with autoimmune-related pancreatitis. To clarify the role of carbonic anhydrase II and lactoferrin, we created animal models of autoimmune pancreatitis by immunizing neonatally thymectomized mice with carbonic anhydrase II and lactoferrin and also by transferring immunized spleen cells to nude mice. Neonatally thymectomized BALB/c mice were immunized with carbonic anhydrase II or lactoferrin followed by three booster injections (n = 10 in each group). We transferred whole, CD4+, or CD8+ spleen cells prepared from immunized neonatally thymectomized mice to nude mice (n = 5 in each group). Gene expression of IFN-gamma and IL-4 was investigated using semiquantitative reverse transcription-polymerase chain reaction. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining was used to examine apoptosis. In immunized neonatally thymectomized mice, the prevalence of inflammation was significantly higher in the pancreas. Inflammation was present in all mice receiving whole or CD4+ cells. There was no change in any of the mice receiving CD8+ cells or nonimmunized spleen cells. Carbonic anhydrase II or lactoferrin-immunized mice had apoptotic duct cells or acinar cells, respectively. Expression of the IFN-gamma gene was up-regulated in each group. Similar findings were observed in the salivary glands and liver. An immunologic mechanism against carbonic anhydrase II or lactoferrin is involved in the pathogenesis of these pancreatitis models, in which the effector cells are Th1-type CD4+ T cells.

PubMed

New cytokine delivery system using gelatin microspheres containing interleukin-10 for experimental inflammatory bowel disease.

Hiroshi Nakase, Kazuichi Okazaki, Yasuhiko Tabata, Makoto Ozeki, Norihiko Watanabe, Masaya Ohana, Suguru Uose, Kazushige Uchida, Toshiki Nishi, Minoru Mastuura, Hiroyuki Tamaki, Toshiyuki Itoh, Chiharu Kawanami, Tsutomu Chiba

The Journal of pharmacology and experimental therapeutics ( AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS ) 301 ( 1 ) 59 - 65 2002年04月 [査読有り] [国際誌]

Interleukin (IL)-10 is an anti-inflammatory cytokine that suppresses the T helper 1 immune response and down-regulates macrophages and monocytes. The therapeutic effect of systemic administration of IL-10 for patients with inflammatory bowel disease, however, has not been satisfactory. We examined whether rectal administration of gelatin microspheres (GM) containing IL-10 (GM-IL-10) prevents colitis in IL-10-deficient (IL-10(-/-)) mice. GM-IL-10 and IL-10 alone were administered rectally. The colon was examined macroscopically and microscopically. IL-12 mRNA expression and CD40 expression in Mac-1-positive cells were also examined. Macroscopic and microscopic examination revealed marked improvement of colitis in IL-10(-/-) mice treated with GM-IL-10. mRNA expression of IL-12 in Mac-1-positive cells in GM-IL-10-treated mice was significantly decreased compared with that in the mice treated with IL-10 alone. Additionally, CD40 expression in Mac-1-positive cells in GM-IL-10-treated mice was decreased more prominently than in mice treated with IL-10 alone. The therapeutic effects of GM-IL-10 were associated with decreased expression of IL-12 mRNA and down-regulation of CD40 expression in Mac-1-positive cells. GM-IL-10 might be useful for treatment of patients with inflammatory bowel disease.

DOI PubMed

Diffuse colon cancer with tumor thrombus in the portal vein.

Hiroshi Nakase, Chiharu Kawanami, Toshiyuki Itoh, Kazuichi Okazaki, Tsutomu Chiba, Toshinao Itani, Jun Mimura, Toshihiko Kawasaki, Hideshi Komori

Gastrointestinal endoscopy ( MOSBY, INC ) 55 ( 2 ) 239 - 40 2002年02月 [査読有り] [国際誌]

DOI PubMed

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