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| 1.
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Takeshima, Eriko ; Tomimori, Koh ; Kawakami, Hirochika ; Ishikawa, Chie ; Sawada, Shigeki ; Tomita, Mariko ; Senba, Masachika ; Kinjo, Fukunori ; Mimuro, Hitomi ; Sasakawa, Chihiro ; Fujita, Jiro ; Mori, Naoki
概要:
[Background] The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity i
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sland (PAI)-dependent activation of nuclear factor-κB (NF-κB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-κB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-κB activation.
[Results] Phosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression. [Conclusion] The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis. 論文 続きを見る |
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| 2.
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Takeshima, Eriko ; Tomimori, Koh ; Teruya, Hiromitsu ; Ishikawa, Chie ; Senba, Masachika ; D' Ambrosio, Daniele ; Kinjo, Fukunori ; Mimuro, Hitomi ; Sasakawa, Chihiro ; Hirayama, Toshiya ; Fujita, Jiro ; Mori, Naoki
概要:
Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that promotes the development of
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T-helper lymphocyte 1 (Th1). Chronic gastritis induced by Helicobacter pylori is considered a Th1-mediated process. IL-12 levels in gastric biopsy samples of H. pylori-infected patients are higher than in those of uninfected individuals, but the cellular source of IL-12 remains elusive. IL-12 staining was detected in mucosal epithelial cells, lymphocytes, and macrophages in specimens of patients with H. pylori-positive gastritis. Therefore, we investigated IL-12 p40 mRNA induction by H. pylori in gastric epithelial cells and T cells. Although cag pathogenicity island (PAI)-positive H. pylori induced IL-12 p40 mRNA expression, an isogenic mutant of the cag PAI failed to induce it in both cell types. Supernatants from H. pylori cultures and H. pylori VacA induced IL-12 p40 mRNA expression in T cells but not in epithelial cells. The activation of the IL-12 p40 promoter by H. pylori was mediated through NF-κB. The transfection of IκB kinase and NF-κB-inducing kinase dominant-negative mutants inhibited H. pylori-induced IL-12 p40 activation. Inhibitors of NF-κB, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and Hsp90 suppressed H. pylori- and VacA-induced IL-12 p40 mRNA expression. The results indicate that H. pylori induces IL-12 p40 expression by the activation of NF-κB, phosphatidylinositol 3-kinase, and p38 mitogen-activated protein kinase. Hsp90 is also a crucial regulator of H. pylori-induced IL-12 p40 expression. In addition to the cag PAI, VacA might be relevant in the induction of IL-12 expression and a Th1-polarized response only in T cells.
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| 3.
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Nakachi, Atsushi ; Karimata, Hiroyuki ; Miyazato, Hiroshi ; Muto, Yoshihiro ; Yamazato, Naoko ; Kinjo, Fukunori
概要:
A 66-year-old man two developed episodes of massive tarry stool and thereafter was admitted to our University Hospital t
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o detect the cause of the tarry stool. An upper gastrointestinal series showed an irregular stricture of the duodenum just distal to the pylorus. Gastroendoscopy revealed a marked stenosis of the pylorus by swelling of the wall and a 2 cm-ulcerated tumor closely adjacent to the pylorus. He underwent a partial distal gastrectomy and a segmental resection of the first portion of the duodenum with a nodal dissection. Grossly, the tumor was an ulcerated carcinoma measuring 2.2×2.7 cm in size and was located in the posterior wall of the duodenum. Histologically, the tumor was confined to the duodenal wall (into the muscularis propria) and showed papillary adenocarcinoma with no evidence of lymph node metastasis. The patient is presently doing well with no recurrence as at the writing of this report.
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| 4.
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安田, 卓 ; 白石, 祐之 ; 大城, 崇司 ; 友利, 健彦 ; 草野, 敏臣 ; 武藤, 良弘 ; 江川, 春彦 ; 戸田, 隆義 ; 金城, 福則 ; Yasuda, Takashi ; Shiraishi, Masayuki ; Oshiro, Takashi ; Tomori, Takehiko ; Muto, Yoshihiro ; Egawa, Haruhiko ; Toda, Takayoshi ; Kinjo, Fukunori
概要:
A case of duodenal stromal tumor (Leiomyosarcoma with low-grade malignancy) in a 45year-old man is herein reported. The
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patient presented with two episodes of massive melena. Endoscopic examination showed a rare, ulcerative tumor of the duodenum proximal to the duodenal papilla with biopsy finding of leiomyoma. He was referred to the University hospital in May, 1997. Diagnostic modalities (Upper GI series, CT, angiography and MRI) confirmed the tumor. At laparotomy the tumor was tightly adhered to the pancreatic head, which makes it impossible to be removed locally. Subsequently, pancreatoduodenectomy was done with reconstruction using Child's procedure. The tumor was ulcerative, relatively well-defined, and 5.5×5cm in size, protruding over the mucosal surface and into the subserosa. The tumor was diagnosed to be a low-grade leiomyosarcoma by histological and immunohistochemical study. He was uneventfull postoperatively and has been enjoying his normal life.
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| 5.
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Nakasone, Hiroki ; Sakugawa, Hiroshi ; Shokita, Hayashi ; Arakaki, Noriko ; Kudeken, Norifumi ; Toyoda, Kazumasa ; Nakayoshi, Tomofumi ; Kawakami, Yuko ; Kinjo, Fukunori ; Saito, Atsushi ; Wakuta, Moriaki ; Uehara, Takeshi
概要:
Fulminant hepatic failure (FHF) is known to have a poor prognosis, particularly in patients with a more gradual onset of
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hepatic encephalopathy (called subacute type). The presence of coagulopathy and the grade of hepatic coma are associated with a worsened prognosis. A 47 year-old woman with subacute type FHF was treated with a combination therapy of plasma exchange and hemodiafiltration, using a high-performance polymethyl metacrylate membrane. After this treatment, she regained consciousness and was stable in the lower hepatic coma grade for a long period (294 days). This survival period was longer than those of 340 patients with FHF who were treated with PE alone, and eventually died of FHF between 1983 and 1988 in Japan.
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| 6.
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Sunagawa, Takashi ; Nakasone, Hiroki ; Kochi, Akihiko ; Sakugawa, Hiroshi ; Kinjo, Fukunori ; Saito, Atsushi ; Morioka, Takamitsu ; Arakaki, Yuusei ; Ito, Etsuo
概要:
An autopsy case of T-cell lymphoma complicated with hemophagocytic syndrome (HPS) is reported. A 60-year-old woman prese
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nting with fever and jaundice was transferred to our hospital. On admission, she showed bicytopenia, severe liver dysfunction and coagulopathy. She subsequently developed pancytopenia. At first, she was suspected of having aplastic anemia. Methylpredonisolone pulse therapy was therefore initiated, and the leukopenia improved. But she later developed leukopenia again, and died of septic shock. At autopsy, proliferation of histiocytes with hemophagocytosis was observed in the reticuloendothelial system. Moreover, T-cell lymphoma was observed. Hence diagnosis of T-cell lymphoma with HPS was made pathologically.
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| 7.
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佐久川, 廣 ; 仲宗根, 啓樹 ; 仲吉, 朝史 ; 川上, 祐子 ; 諸喜田, 林 ; 新村, 政昇 ; 照屋, 寛 ; 前原, 信人 ; 金城, 渚 ; 外間, 昭 ; 大城, 淳一 ; 金城, 福則 ; 斎藤, 厚 ; 山城, 章裕 ; 上地, 博之 ; 親泊, 康朝 ; 石原, 昌清 ; 嘉手納, 啓三 ; 大湾, 朝二 ; 宮平, 守博 ; 池間, 稔 ; 仲吉, 朝邦 ; 与儀, 裕 ; 小波津, 寛 ; 中村, 博 ; 城間, 健治 ; 比嘉, 昌文 ; 平山, 良克 ; 上原, 剛 ; Sakugawa, Hiroshi ; Nakasone, Hiroki ; Nakayoshi, Tomofumi ; Kawakami, Yuko ; Shokita, Hayashi ; Niimura, Seisho ; Teruya, Hiroshi ; Maehara, Nobuto ; Kinjo, Nagisa ; Hokama, Akira ; Ohshiro, Junichi ; Kinjo, Fukunori ; Saito, Atsushi ; Yamashiro, Akihiro ; Uechi, Hiroyuki ; Oyadomari, Yasutomo ; Ishihara, Masakiyo ; Kadena, Keizo ; Ohwan, Choji ; Miyahira, Morihiro ; Ikema, Minoru ; Nakayoshi, Tomokuni ; Yogi, Yutaka ; Kohatsu, Hiroshi ; Nakamura, Hiroshi ; Shiroma, Kenji ; Higa, Masafumi ; Hirayama, Yoshikatsu ; Uehara, Takeshi
概要:
Five different dosage regimens of recombinant interferon ($ \gamma $IFN) alfa-2 b were compared in patients with chronic
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hepatitis C. Ninety-four patients were assigned to one of five groups: group 1, 2 and 3 were given 3, 6 and 10 million units (MU) , respectively, of $ \gamma $IFN alfa-2b daily for 2 weeks, followed by thrice weekly for 22 weeks (total dose: 240, 480 and 800 MU) , respectively. Group 4 and 5 were given 10 MU of $ \gamma $IFN alfa-2b daily for 2 weeks, followed by 10 MU thrice weekly for 12 weeks (group 4) or 6 MU thrice weekly for 22 weeks (group 5), with a total dose of480 and 536 MU, respectively. Sustained response to $ \gamma $IFN was seen in 7.7% (1/13) of patients in group 1. The rate was significantly lower than that of either group 2 or 3 (p<0. 05 in each comparison). There was no difference in the sustained response rate between group 2 and 3 (38.0%vs 44.0%). Comparison of the efficacy of group 4 or 5 with those of the other groups was not appropriate because of the small number of patients assigned in group 4 or 5. When the sustained response rate of patients infected with genotype 1b, which was known to be resistent to IFN treatment, is compared between group 2 and 3, higher response rate was seen in group 3 (26.3% in group 2 vs 42.1% in group 3), although not significantly.
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| 8.
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諸喜田, 林 ; 金城, 福則 ; 仲吉, 朝史 ; 仲宗根, 啓樹 ; 新村, 政昇 ; 金城, 渚 ; 幸地, 昭彦 ; 大城, 淳一 ; 斎藤, 厚 ; 真喜志, 金造 ; 我喜屋, 出 ; Syokita, Hayashi ; Kinjo, Fukunori ; Nakayoshi, Tomofumi ; Nakasone, Hiroki ; Nimura, Seisho ; Kinjo, Nagisa ; Kohchi, Akihiko ; Ohshiro, Junichi ; Saito, Atsushi ; Makishi, Kinzo ; Gakiya, Izuru
概要:
A 49-year-old male with diabetes mellitus was diagnosed with an abnormality of the stomach during a medical examination.
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Radiographic and gastroscopic examinations revealed a submucosal tumor (SMT) on the anterior wall of the gastric antrum. The SMT was examined by endoscopic ultrasonography (EUS), which showed a slightly hypo-echoic lesion in the second and third layers of the gastric antrum wall. In addition, after injection of the saline solution into the third layer, the tumor was revealed to be apart from the muscular layer by EUS. The histological diagnosis of inflammatory fibroid polyp was obtained after endoscopic polypectomy.
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| 9.
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Nakasone, Hiroki ; Sgkuawa, Hiroshi ; Nakayoshi, Tmofumi ; Kawakami, Yuko ; Kinjo, Fukunori ; Saito, Atushi ; Yamashiro, Akiko ; Nakayoshi, Tmokuni ; Ikema, Minoru ; Hirayama, Yoshikatsu
概要:
The present study examined the efficacy and the predicting factors of response to interferon (IFN) alpha in patients wit
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h liver cirrhosis associated with hepatitis type C virus infection (LC type C). Sixty-seven patients were treated with IFN alpha and were classified into 2 Groups. Group 1 : Patients with liver cirrhosis, showing histological liver cirrhosis or chronic active hepatitis with lobular disorganization. Group 2 : Patients with chronic hepatitis, showing histological chronic persistent hepatitis or chronic active hepatitis without lobular disorganization. Sustained response to IFN was obtained in 5/17 (29.4%) and 24/50 (48%) of patients in Group 1 and Group 2, respectively. However, the difference was not significant. All patients in Group 2 showed a significant decrease in alanine aminotransferase (ALT) levels during the treatment, whereas 5 of the 17 patients in Group 1 showed no response. All sustained responders in Group 1 who were tested for serum HCV-RNA titer showed low serum HCV-RNA titer, which was less than 10^7 copies/ml, while all except one patient of the non-responders of Group 1 showed above 10^8 copies/ml. It is said that patients with LC type C are more resistant to IFN treatment compared to those with chronic hepatitis type C. However, our findings suggest that even in patients with LC type C, low serum HCV-RNA levels might be associated with better response to IFN.
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| 10.
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Sakugawa, Hiroshi ; Nakasone, Hiroki ; Kawakami, Yuko ; Nakayoshi, Tomofumi ; Kinjo, Fukunori ; Saito, Atsushi ; Ikema, Minoru ; Yamashiro, Akihiro ; Nakayoshi, Tomokuni
概要:
To compare the clinical utility of type IV collagen 7S domain and hyaluronate, as markers in the evaluation of liver fib
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rosis, 184 patients with biopsy-proven chronic viral liver disease (32; type B, 152; type C) were involved in this study. The two markers correlated well with the grade of liver fibrosis. The correlation coefficients of 7S-collagen and hyaluronate with the extent of fibrosis were 0.747 and 0.813, respectively. Very high values were seen more frequently in hyaluronate than in 7S-collagen, particularly in patients with moderate and severe fibrosis. Both markers also correlated strongly with conventional liver function tests except for alanine aminotransferase. In conclusion, serum hyaluronate was a more sensitive marker and seemed to more strongly correlate with the degree of hepatic fibrosis than type IV collagen 7S domain.
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