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Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma

Protein & Cell 2010年第8期1卷 711-717页

作者： Takuma Hayashi Akiko Horiuchi kenji sano Nobuyoshi Hiraoka Yae Kanai Tanri Shiozawa Susumu Tonegawa Ikuo Konishi Department of Immunology and Infectious Disease Shinshu University Graduate School of MedicineMatsumotoNagano 390-8621Japan Department of Obstetrics and Gynecology Shinshu University School of MedicineMatsumotoNagano 390-8621Japan Department of Laboratory Medicine Shinshu University HospitalMatsumotoNagano 390-8621Japan Pathology Division National Cancer Center Research InstituteTokyo 104-0045Japan Picower Institution and Department of Biology Massachusetts Institute of TechnologyCambridgeMassachusetts 02139USA Department of Obstetrics and Gynecology Kyoto University Graduate School of MedicineSakyo-kuKyoto 606-8501Japan Promoting Business using Advanced Technology Japan Science and Technology Agency(JST)Kawaguchi-shiSaitama 332-0012Japan

Uterine tumors are the most common type of gynecologic neoplasm.Uterine leiomyosarcoma(LMS)is rare,accounting for 2%to 5%of tumors of the uterine body.Uterine LMS develops more often in the muscle tissue layer of the uterine body than in the uterine cervix.The development of gynecologic tumors is often correlated with female hormone secretion;however,the development of uterine LMS is not substantially correlated with hormonal conditions,and the risk factors are not yet known.Radiographic evaluation combined with PET/CT can be useless in the diagnosis and surveillance of uterine LMS.Importantly,a diagnostic biomarker,which distinguishes malignant LMS and benign tumor leiomyoma(LMA)is yet to be established.Accordingly,it is necessary to analyze risk factors associated with uterine LMS in order to establish a method of treatment.LMP2-deficient mice spontaneously develop uterine LMS,with a disease prevalence of~40%by 14 months of age.It is therefore of interest whether human uterine LMS shows a loss of LMP2 expression.We found LMP2 expression is absent in human LMS,but present in human LMA.Therefore,defective LMP2 expression may be one of the risk factors for LMS.LMP2 is potentially a diagnostic biomarker for uterine LMS,and gene therapy with LMP2-encording DNA may be a new therapeutic approach.

关键词： LMP2 uterine leiomyosarcoma uterine leiomyoma diagnostic biomarker

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Non-alcoholic fatty liver disease later diagnosed as myotonic dystrophy

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World Journal of Hepatology 2020年第9期12卷 685-692页

作者： Naoki Tanaka Takefumi Kimura Naoyuki Fujimori Yasuyuki Ichise kenji sano Akira Horiuchi Department of Metabolic Regulation Shinshu University School of MedicineMatsumoto 390-8621Japan Department of Gastroenterology Shinshu University School of MedicineMatsumoto 390-8621Japan Digestive Disease Center Showa Inan General HospitalKomagane 399-4117Japan Department of Pathology Iida Municipal HospitalIida 395-8502Japan

BACKGROUND Myotonic dystrophy(MD)is sometimes accompanied by metabolic/endocrine disorders,including dyslipidemia,central obesity,and hypogonadism.Due to considerable individual differences in the severity and progression of myopathy,MD patients with minimal-to-mild muscle symptoms might be followed as having other diseases,such as non-alcoholic fatty liver disease(NAFLD).CASE SUMMARY A 40-year-old non-obese man without a history of regular ethanol consumption was referred to our hospital due to persistent liver dysfunction and hyperlipidemia.His body mass index was 23.4 kg/m2.Liver histology demonstrated macrovesicular steatosis,ballooned hepatocytes with eosinophilic inclusion bodies,and perisinusoidal fibrosis,leading to the diagnosis of nonalcoholic steatohepatitis(NASH).Although he had no discernable muscle pain or weakness,persistently high serum creatine kinase(CK)and myoglobin levels as well as the presence of frontal baldness,a hatched face,history of cataract surgery,and grip myotonia indicated the possibility of MD.Southern blotting of the patient’s DNA revealed the presence of CTG repeats,confirming the diagnosis.CONCLUSION When gastroenterologists encounter NAFLD/NASH patients,serum CK should be verified.If hyperCKemia,frontal baldness,a hatched face,history of cataract surgery,and grip myotonia are noted,the possibility of MD may be considered.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Frontal baldness Cataract Creatine kinase

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Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2018年第11期24卷 1239-1249页

作者： Naoyuki Fujimori Takeji Umemura Takefumi Kimura Naoki Tanaka Ayumi Sugiura Tomoo Yamazaki Satoru Joshita Michiharu Komatsu Yoko Usami kenji sano Koji Igarashi Akihiro Matsumoto Eiji Tanaka Department of Internal Medicine Division of GastroenterologyShinshu University School of MedicineMatsumoto 390-8621Japan Department of Metabolic Regulation Shinshu University Graduate School of MedicineMatsumotoJapanand Research Center for Agricultural Food IndustryShinshu UniversityMatsumoto390-8621Japan Department of Laboratory Medicine Shinshu University HospitalMatsumoto 390-8621Japan Bioscience Division TOSOH CorporationKanagawa 252-1123Japan

AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD.

关键词： Autotaxin Non-alcoholic fatty liver disease Fibrosis Ballooning

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Association between endotoxemia and histological features of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2017年第4期23卷 712-722页

作者： Hiroyuki Kitabatake Naoki Tanaka Naoyuki Fujimori Michiharu Komatsu Ayaka Okubo Kyogo Kakegawa Takefumi Kimura Ayumi Sugiura Tomoo Yamazaki Soichiro Shibata Yuki Ichikawa Satoru Joshita Takeji Umemura Akihiro Matsumoto Masayoshi Koinuma kenji sano Toshifumi Aoyama Eiji Tanaka Department of Metabolic Regulation Shinshu University Graduate School of Medicine Department of Internal Medicine Division of GastroenterologyShinshu University School of Medicine Center for Clinical Research Shinshu University Hospital Faculity of Pharmaceutical Sciences Teikyo Heisei University Department of Laboratory Medicine Shinshu University Hospital

AIM To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features ofnonalcoholic fatty liver disease(NAFLD).METHODS One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide(LPS)-binding protein(LBP) and anti-endotoxin core immunoglobulin G(Endo Cab Ig G) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores. RESULTS Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis(NASH) patients as compared with nonalcoholic fatty liver(NAFL) subjects and was correlated with steatosis(r = 0.38, P < 0.0001) and ballooning scores(r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum Endo Cab Ig G concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between Endo Cab Ig G and histological findings. CONCLUSION LBP/Endo Cab Ig G were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.

关键词：不含酒精的 steatohepatitis Endotoxemia Lipopolysaccharide 有约束力的蛋白质 EndoCab IgG 纤维变性脂肪变性

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民俗学的新时代:通往“世界常民学”之路

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民间文化论坛 2023年第5期 66-77页

作者： [日]佐野贤治蒋明超(译) 泰山学院泰山研究院

柳田国男、石田英一郎、竹田旦、直江广治、千叶德尔、宫本馨太郎、和歌森太郎、樱井德太郎、宫田登、福田亚细男等日本民俗学界的前辈们,通过不断提出质问的方式推动了20世纪日本民俗学的发展。从进入大学后,佐野贤治亲历了从竹田旦、... 详细信息

柳田国男、石田英一郎、竹田旦、直江广治、千叶德尔、宫本馨太郎、和歌森太郎、樱井德太郎、宫田登、福田亚细男等日本民俗学界的前辈们,通过不断提出质问的方式推动了20世纪日本民俗学的发展。从进入大学后,佐野贤治亲历了从竹田旦、直江广治、千叶德尔到宫田登,再到福田亚细男的几次民俗学变革。通过逾半个世纪的学习与实践,佐野贤治在继承柳田民俗学的基础上,从事比较民俗学、佛教与民俗及民具等方面的研究对其进行了补足。最后佐野贤治提出对21世纪民俗学研究的展望,即超越“一国民俗学”的“世界常民学”研究。--译者.

关键词：柳田民俗学世界常民学比较民俗学民具研究

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Asymptomatic Anisakiasis of the Colon Diagnosed and Treated by Colonoscopy

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Case Reports in Clinical Medicine 2020年第9期9卷 288-294页

作者： Tomoshi Takeda kenji Niwa Akie sano Atsunori Kodama Kuninori Hatasa Yasunari Matsuno Masao Kagami Motoki Takenaka Kohjiro Niwa Takuji Tanaka Department of Internal Medicine Gujo City Hospital Shimadani Gujo City Gifu Japan Section of Laboratory Medicine and Obstetrics & Gynecology Gujo City Hospital Shimadani Gujo City Gifu Japan sano Internal Medicine Clinic Naka-fukuno-cho Seki City Gifu Japan Department of Obstetrics & Gynecology Gifu University School of Medicine Yanagido Gifu City Japan Department of Internal Medicine Kizawa Memorial Hospital Shimokobi Kobicho Minokamo City Japan Department of Diagnostic Pathology & Research Center of Diagnostic Pathology Gifu Municipal Hospital Gifu City Japan

Anisakiasis can involve any part of the digestive tract, but most cases reported have involved the stomach;few reports have described colonic anisakiasis. Furthermore, asymptomatic colonic anisakiasis has been reported to be very rare. A 58-year-old Japanese male asymptomatically received colonoscopy due to a fecal occult blood testing positive, and an Anisakis larva was removed in the ascending colon. After colonoscopy, an detailed questionings concerning eating raw fish revealed that the patient ate the liver of raw filefish 21 days before the colonoscopy. Thus, questionings concerning eating the raw fish were very important and helpful for correct diagnosis. This case report demonstrated that colonic anisakiasis can be diagnosed by colonoscopy before severe complications (intestinal obstruction, perforation, and cancer development) occur. Also, biopsy forceps could be used to remove the Anisakis worms, demonstrating that diagnosis and treatment can be simultaneously performed.

关键词： Asymptomatic Anisakiasis Ascending Colon Colonoscopy Risk Factor for Cancer

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