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Mina Hamano,
Yoshihiro Kamada,
Shinichi Kiso,
Kunimaro Furuta,
Takashi Kizu,
Norihiro Chatani,
Mayumi Egawa,
Takayo Takemura,
Hisao Ezaki,
Yuichi Yoshida, [......],
Aiko Furubayashi,
Kazuo Kinoshita, Osamu Kishida,
Takashi Fujimoto,
Akira Yamada,
Yoshifumi Tsukamoto,
Shusaku Tsutsui,
Tetsuo Takehara,
Norio Hayashi,
Yuji Matsuzawa
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ABSTRACT: Aim: Central obesity, insulin resistance and alcohol consumption are thought to be major risk factors for fatty liver formation. Adiponectin (APN) prevents fatty liver formation, and its serum levels are lower in subjects with central obesity and/or insulin resistance. The aim of this study was to explore the association among serum APN levels, central obesity, insulin resistance and liver dysfunction with or without fatty liver classified by alcohol consumption in healthy subjects. Methods: A total of 5588 Japanese male subjects who underwent a health check-up were classified into three groups according to alcohol consumption: non- or light drinkers (15 g/day ≥ ethanol); mild drinkers (15 g/day < ethanol ≤ 30 g/day); and moderate- or heavy drinkers (30 g/day < ethanol). Central obesity and insulin resistance were assessed by waist circumference (WC) and Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), respectively. Results: WC was significantly increased, while HOMA-IR was significantly decreased according to the extent of alcohol consumption. Serum alanine aminotransferase levels were significantly lower and serum APN levels were significantly higher in mild drinkers than in the other two groups. Multiple linear regression analysis showed that serum APN level served as the significant and independent determinant for liver dysfunction in the subjects with fatty liver, irrespective of alcohol consumption. However, WC became a non-significant determinant of liver dysfunction as alcohol consumption increased. Conclusion: Hypoadiponectinemia is a significant determinant for steatotic dysfunction for all levels of alcohol consumption, but central obesity was not a significant determinant for alcoholic fatty liver-induced liver dysfunction.
Hepatology Research 07/2012; · 2.20 Impact Factor
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Motohiko Kato,
Kenji Watabe,
Toshimitsu Hamasaki,
Miyuki Umeda,
Aiko Furubayashi,
Kazuo Kinoshita, Osamu Kishida,
Takashi Fujimoto,
Akira Yamada,
Yoshifumi Tsukamoto,
Shunsuke Yamamoto,
Yoshihiro Kamada,
Yuichi Yoshida,
Shinichi Kiso,
Shusaku Tsutsui,
Shinji Kihara,
Norio Hayashi,
Yuji Matsuzawa
[show abstract]
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ABSTRACT: Obesity is a risk factor for gastro-esophageal reflux disease (GERD). It is generally considered that intra-abdominal pressure in obese subjects is involved in the pathogenesis of GERD through acid exposure to the esophagus. Recently, visceral fat has been recognized as an endocrine organ that secretes various adipocytokines including adiponectin. The aim of this study was to elucidate the relation between adiponectin and erosive esophagitis.
This was a cross-sectional retrospective observational study: 2405 consecutive subjects who underwent screening esophago-gastro-duodenoscopy with serum adiponectin measurement as part of their physical check-up programs were analyzed. Clinical factors were compared between subjects with and without erosive esophagitis. The association between adiponectin and erosive esophagitis was assessed using a bootstrapping re-sampling method after adjustment for factors that tended to be different in univariate analysis.
Serum adiponectin levels were significantly lower in those with erosive esophagitis (8.17 μg/ml) than in those without (10.1). The erosive esophagitis group had a greater body mass index (BMI) and waist circumference (WC) and a higher prevalence of hiatal hernia. Using the bootstrap method, with a lower adiponectin cut-off value of 3-7 μg/ml, the lower limit of the 95% confidence interval of the adjusted odds ratio consistently exceeded 1 after adjustment for BMI and hiatal hernia in men. When adjusting for WC instead of BMI, the effect of adiponectin was reduced but remained significant at a lower cut-off value (3-3.5 μg/ml).
Low serum adiponectin levels may be associated with an increased risk for erosive esophagitis in men.
Journal of Gastroenterology 08/2011; 46(12):1361-7. · 4.16 Impact Factor
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Shunsuke Yamamoto,
Kenji Watabe,
Shusaku Tsutsui,
Shinichi Kiso,
Toshimitsu Hamasaki,
Motohiko Kato,
Yoshihiro Kamada,
Yuichi Yoshida,
Shinji Kihara,
Miyuki Umeda,
Aiko Furubayashi,
Kazuo Kinoshita, Osamu Kishida,
Takashi Fujimoto,
Akira Yamada,
Yoshifumi Tsukamoto,
Norio Hayashi,
Yuji Matsuzawa
[show abstract]
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ABSTRACT: Obesity is recently known as a risk factor for endoscopic gastritis. Adiponectin is an anti-inflammatory cytokine secreted from fat tissue, and its serum concentrations are reduced in obesity. The relation between adiponectin and gastritis remains unclear.
The aim of this study was to determine whether lower serum adiponectin level is associated with the risk of endoscopic gastritis.
We analyzed medical records of participants of a routine health check-up examination. Association among endoscopic findings, serum adiponectin level, and other clinical factors including age, sex, alcohol habit, smoking habit, body mass index (BMI), blood pressure, cholesterol, triglyceride, glucose, and insulin were investigated. Endoscopic erosive gastritis was defined as a flat or minimally depressed white spot surrounded by a reddish area or small elevation with central umbilications mimicking octopus' suckers.
A total of 2,400 participants were enrolled. BMI was significantly higher in gastritis-positive participants than in gastritis-negative participants. Serum adiponectin levels were significantly lower in gastritis-positive participants than in gastritis-negative participants. Multivariate logistic regression analysis revealed that lower serum adiponectin level (OR 0.96; 95% CI 0.93-0.99), smoking (OR 0.50; 95% CI 0.30-0.80), higher blood pressure (OR 1.02; 95% CI 1.01-1.03), and duodenitis (OR 1.8; 95% CI 1.00-3.09) were significantly associated with endoscopic erosive gastritis.
Lower serum level of adiponectin may increase the risk of endoscopic erosive gastritis, independently of BMI. Our findings facilitate further study to clarify the role of hypoadiponectinemia in erosive gastritis.
Digestive Diseases and Sciences 03/2011; 56(8):2354-60. · 2.12 Impact Factor
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Osamu Kishida,
Yoshiji Miyazaki,
Yoko Murayama,
Miyuki Ogasa,
Tamana Miyazaki,
Takahiro Yamamoto,
Kenji Watabe,
Shusaku Tsutsui,
Tatsuya Kiyohara,
Iichiro Shimomura,
Yasuhisa Shinomura
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ABSTRACT: The epidermal growth factor receptor (EGFR) and its ligands are involved in tumor growth, metastasis, angiogenesis, and resistance to chemotherapy. The findings reported here demonstrate that SN38 (the active metabolite of CPT-11) induces the tyrosine phosphorylation of EGFR within 5 min, followed by the induction of transcripts and/or proteins of the heparin-binding EGF-like growth factor, amphiregulin, transforming growth factor-alpha, and interlukin-8 (IL-8) in AGS gastric cancer cells. SN38 also activates nuclear factor-kappa B and activator protein-1, both of which are critical for the transcription of the IL-8 gene. However, the blocking of EGFR activation by gefitinib ("Iressa", ZD1839), an EGFR-TKI (tyrosine kinase inhibitor), abrogates all the above reactions. The SN38-triggered mechanisms include the generation of reactive oxygen species (ROS) and the activation of protein kinase C (PKC), followed by metalloproteinase activation and the sequential ectodomain shedding of EGFR ligands. These findings suggest that EGF signaling is enhanced by CPT-11 and point to the potential benefit of the use of a combination of CPT-11 with gefitinib in the treatment of certain gastric cancers.
Cancer Chemotherapy and Pharmacology 05/2005; 55(4):393-403. · 2.83 Impact Factor
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Yoko Murayama,
Jun-ichiro Miyagawa,
Kenji Oritani,
Hitoshi Yoshida,
Katsumi Yamamoto, Osamu Kishida,
Tamana Miyazaki,
Shusaku Tsutsui,
Tatsuya Kiyohara,
Yoshiji Miyazaki,
Shigeki Higashiyama,
Yuji Matsuzawa,
Yasuhisa Shinomura
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ABSTRACT: CD9, a member of the tetraspanin family, has been shown to be involved in a range of cellular activities, including migration, proliferation and adhesion, but the molecular mechanisms by which it mediates such events is unclear. Here, we found that anti-CD9 monoclonal antibody ALB6 inhibited cell proliferation, reduced cell viability and induced not only morphological changes specific to apoptosis but also molecular changes, as evidenced by TUNEL and annexin-V staining. For the possible mechanism of ALB6-induced apoptosis, ALB6 activated the c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 mitogen-activated-protein kinase (MAPK) within 5-15 minutes, as well as caspase-3 within 24-48 hours. It is noteworthy that ALB6 induced tyrosine phosphorylation of the p46 Shc isoform specifically and that the overexpression of its dominant-negative form completely suppressed the ALB6-induced activation of JNK/SAPK, p38 MAPK and caspase-3, resulting in the inhibition of apoptotic cell death. These results suggest that CD9 might regulate apoptosis through the specialized signals in human cancer cell lines.
Journal of Cell Science 08/2004; 117(Pt 15):3379-88. · 6.11 Impact Factor
