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Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance

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World Journal of Diabetes 2017年第3期8卷 97-103页

作者： Tomoki abe Katsuya Hirasaka takeshi Nikawa Department of Nutritional Physiology Institute of Biomedical Sciences Tokushima University Graduate School Graduate School of Fisheries Science and Environmental Studies Nagasaki University

Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance(IR). Macrophages infiltrate the adipose tissue(AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4(TLR4) and induce inflammatory responses in AT macrophages(ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b(Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs.

关键词： Casitas b-lineage lymphoma-b Insulin resistance Macrophage Obesity Toll-like receptor 4

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World Journal of Gastroenterology 2010年第20期16卷 2484-2495页

作者： Mitsuro Chiba Toru abe Hidehiko Tsuda takeshi Sugawara Satoko Tsuda Haruhiko Tozawa Katsuhiko Fujiwara Hideo Imai Division of Gastroenterology Nakadori General HospitalAkita 010-8577Japan

AIM: To investigate whether semi-vegetarian diet (SVD) has a preventive effect against relapse of Crohn’s disease (CD) in patients who have achieved remission,who are a high-risk group for ***: A prospective,single center,2-year clinical trial was ***-two adult CD patients who achieved clinical remission either medically (n = 17) or surgically (n = 5) and consumed an SVD during hospitalization were advised to continue with an SVD and avoid known high-risk foods for inflammatory bowel *** primary endpoint was clinical relapse defi ned as the appearance of active symptoms of ***-Meier survival analysis was used to calculate the cumulative proportion of patients who had a relapse.A 2-year analysis of relapse rates of patients who followed an SVD and those who did not (an omnivorous diet group) was ***: SVD was continued by 16 patients (compliance 73%).Remission was maintained in 15 of 16 patients (94%) in the SVD group vs two of six (33%)in the omnivorous *** rate with SVD was 100% at 1 year and 92% at 2 *** showed signif icant prevention in the time to relapse compared to that in the omnivorous group (P = 0.0003,log rank test).The concentration of C-reactive protein was normal at the f inal visit in more than half of the patients in remission who were taking an SVD,who maintained remission during the study (9/15;60%),who terminated follow-up (8/12;67%),and who completed 2 years follow-up (7/10;70%).There was no untoward effect of ***: SVD was highly effective in preventing relapse in CD.

关键词： Crohn’s disease Inflammatory bowel disease Vegetarian diet Recurrence Lifestyle

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

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World Journal of Gastroenterology 2016年第40期22卷 8862-8868页

作者： takeshi Yokoo Kenya Kamimura Hiroyuki abe Yuji Kobayashi Tsutomu Kanefuji Kohei Ogawa Ryo Goto Masafumi Oda takeshi Suda Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Institute for Research Collaboration and Promotion Niigata University

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vectormediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

关键词： Gene therapy liver Hydrodynamic gene delivery Non-viral image-guided

Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances

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World Journal of Hepatology 2022年第4期14卷 778-790页

作者： takeshi Suda Ai Sugimoto Tsutomu Kanefuji Atsushi abe takeshi Yokoo Takahiro Hoshi Satoshi abe Shinichi Morita Kazuyoshi Yagi Masashi Takahashi Shuji Terai Department of Gastroenterology and Hepatology Uonuma Institute of Community MedicineNiigata University Medical and Dental HospitalMinami Uonuma 949-7302NiigataJapan Division of Thoracic and Cardiovascular Surgery Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8122Japan Department of Gastroenterology and Hepatology Tsubame Rosai HospitalTsubame 959-1228NiigataJapan Department of Administration Joetsu-Area General Health Care CenterJoetsu 943-0803NiigataJapan Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life Niigata University School of MedicineNiigata 951-8122Japan Division of Gastroenterology and Hepatology School of Medical and Dental SciencesNiigata UniversityNiigata 951-8122Japan

BACKGROUND As survival has been prolonged owing to surgical and medical improvements,liver failure has become a prognostic determinant in patients with congestive heart *** hepatopathy,an abnormal state of the liver as a result of congestion,insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological *** measurements of shear wave elastography cannot qualify liver fibrosis,which is a prognosticator in any type of chronic liver disease,in cases of congestion because congestion makes the liver stiff without *** hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural *** establish a strategy measuring liver stiffness as a reflection of architectural rigidity under *** Two-dimensional shear wave elastography(2dSWE)was measured in the supine(Sp)and left decubitus(Ld)positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver *** of interest were placed at twelve sites,and the median and robust coefficient of variation were *** data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple *** inferior vena cava(IVC)diameters at different body positions were compared using the Wilcoxon matched pairs signed rank *** number of cases with cardiothoracic ratios greater than or not greater than 50%was compared using Fisher’s exact test.A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation *** The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld(LdSWE)than in Sp(SpSWE)(P=0.007,(average±SD)13.9±3.6 vs 13.1±3.4 mm)but not in those with lower LdSWE values(P=0.32,13.3±3.5 vs 13.0±3.5 mm).In 81 subjects,SpSWE was increased or decreased in

关键词： Shear wave elastography Inferior vena cava diameter Congestive hepatopathy Liver fibrosis Body positions Fibrosis-4 index

Lansoprazole-associated collagenous colitis:Diffuse mucosal cloudiness mimicking ulcerative colitis

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World Journal of Gastroenterology 2009年第17期15卷 2166-2169页

作者： Mitsuro Chiba takeshi Sugawara Haruhiko Tozawa Hidehiko Tsuda Toru abe Takuo Tokairin Iwao Ono Eriko Ushiyama Division of Gastroenterology Nakadori General Hospital Akita 010-8577 Japan Department of Pathology Nakadori General Hospital Akita 010-8577 Japan Department of Internal Medicine Nakadori Rehabilitation Hospital Akita 010-8577 Japan

There have only been a few reports on lansoprazole-associated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimicking ulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis. Consequently sulfasalazine 2 g/d was started. The patient's diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infi ltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Five months later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea. Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.

关键词： Collagenous colitis Microscopic colitis,Lansoprazole Ulcerative colitis Sulfasalazine

A case of intrahepatic clear cell cholangiocarcinoma

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World Journal of Gastroenterology 2010年第20期16卷 2571-2576页

作者： Eo Toriyama Atsushi Nanashima Hideyuki Hayashi Kuniko abe Naoe Kinoshita Shunsuke Yuge takeshi Nagayasu Masataka Uetani Tomayoshi Hayashi Department of Pathology Nagasaki University HospitalNagasaki 852-8501Japan Division of Surgical 4Oncology Nagasaki University Graduate School of Biomedical SciencesNagasaki 852-8523Japan Department of Radiological Sciences Nagasaki University Graduate School of Bio-medical SciencesNagasaki 852-8523Japan

Intrahepatic clear cell cholangiocarcinoma is very rareonly 8 cases have been reported.A 56-year-old Japanese man with chronic hepatitis B infection was diagnosed with a 2.2 cm hepatocellular carcinoma on imaging,and hepatic segmentectomy was ***,the tumor cells had copious clear cytoplasm and formed glandular structures or solid *** pathological findings suggested the tumor was a clear cell variant of intrahepatic *** stains and radiological images suggested that the cause of the clear cell change had been glycogen,not mucin nor *** immunohistochemical staining,cytokeratin(CK)7 and CK19 were positive,whereas CK20 was *** was detected on the cell membranes,and CD56 was focally *** patient was given adjuvant chemotherapy and is currently free from the tumor 7 mo *** follow-up with adequate postoperative supplementary chemotherapy is necessary because the characteristics of this type of tumor are unknown.

关键词： Intrahepatic cholangiocarcinoma Clear cell carcinoma Glycogen Mucin Lipid Hepatectomy

Rational arrangement of measuring shear wave speed in the liver

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World Journal of Gastroenterology 2019年第20期25卷 2503-2513页

作者： takeshi Yokoo Tsutomu Kanefuji takeshi Suda Itsuo Nagayama Takahiro Hoshi Satoshi abe Shinichi Morita Hiroteru Kamimura Kenya Kamimura Atsunori Tsuchiya Masaaki Takamura Kazuyoshi Yagi Shuji Terai Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life Niigata University School of MedicineNiigataNiigata 951-8122Japan Division of Gastroenterology and Hepatology Niigata Tokamachi HospitalTokamachiNiigata 948-0065Japan Department of Gastroenterology and Hepatology Uonuma Institute of Community MedicineNiigata University Medical and Dental HospitalMinami UonumaNiigata 949-7302Japan Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8122Japan

BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and twodimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001),and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.

关键词： Liver stiffness Ultrasound Shear wave elastography Acoustic radiation force impulse Heterogeneity

Endoscopic submucosal dissection for colorectal neoplasms:A review

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World Journal of Gastroenterology 2014年第43期20卷 16153-16158页

作者： Taku Sakamoto Genki Mori Masayoshi Yamada Yuzuru Kinjo Eriko So Seiichiro abe Yosuke Otake takeshi Nakajima Takahisa Matsuda Yutaka Saito Endoscopy Division National Cancer Center Hospital

The introduction of colorectal endoscopic submucosal dissection(ESD)has expanded the application of endoscopic treatment,which can be used for lesions with a low metastatic potential regardless of their *** has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal ***,in the past,surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum,regardless of the depth of invasion,as endoscopic resection of these lesions was technically ***,a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal *** the other hand,ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty,longer procedural duration,and increased risk of *** diversify the available endoscopic treatment strategies for superficial colorectal neoplasms,endoscopists performing ESD need torecognize its indications,the technical issues involved in its application,and the associated *** review outlines the methods and type of devices used for colorectal ESD,and the training required by endoscopists to perform this procedure.

关键词： Colorectum Endoscopic submucosal dissection Short-term outcomes Training indication for endoscopic treatment

Tracing founder haplotypes of Japanese apple varieties: application in genomic prediction and genome-wide association study

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Horticulture Research 2021年第1期8卷 614-627页

作者： Mai FMinamikawa Miyuki Kunihisa Koji Noshita Shigeki Moriya Kazuyuki abe takeshi Hayashi Yuichi Katayose Toshimi Matsumoto Chikako Nishitani Shingo Terakami Toshiya Yamamoto Hiroyoshi Iwata Laboratory of Biometry and Bioinformatics Department of Agricultural and Environmental BiologyGraduate School of Agricultural and Life SciencesThe University of Tokyo1-1-1 YayoiBunkyoTokyo 113-8657Japan Institute of Fruit Tree and Tea Science National Agriculture and Food Research Organization(NARO)2-1 FujimotoTsukubaIbaraki 305-8605Japan Division of Apple Research Institute of Fruit Tree and Tea ScienceNARO92-24 Shimokuriyagawa NabeyashikiMoriokaIwate 020-0123Japan Institute of Crop Science NARO2-1-2 KannondaiTsukubaIbaraki 305-8518Japan Institute of Agrobiological Sciences NARO1-2 OwashiTsukubaIbaraki 305-8634Japan

Haplotypes provide useful information for genomics-based approaches,genomic prediction,and genome-wide association *** a small number of superior founders have contributed largely to the breeding history of fruit trees,the information of founder haplotypes may be relevant for performing the genomics-based approaches in these *** this study,we proposed a method to estimate 14 haplotypes from 7 founders and automatically trace the haplotypes forward to apple parental(185 varieties)and breeding(659 F 1 individuals from 16 full-sib families)populations based on 11,786 single-nucleotide polymorphisms,by combining multiple ***,92%of the single-nucleotide polymorphisms information in the parental and breeding populations was characterized by the 14 founder *** use of founder haplotype information improved the accuracy of genomic prediction in 7 traits and the resolution of genome-wide association study in 13 out of 27 fruit quality traits analyzed in this *** also visualized the significant propagation of the founder haplotype with the largest genetic effect in genome-wide association study over the pedigree tree of the parental *** results suggest that the information of founder haplotypes can be useful for not only genetic improvement of fruit quality traits in apples but also for understanding the selection history of founder haplotypes in the breeding program of Japanese apple varieties.

关键词： breeding varieties prediction