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Efficacy and HCC development after DAA therapy for patients with chronic hepatitis C:a single center retrospective cohort study

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Hepatoma Research 2017年第10期3卷 215-220页

作者： akitoshi douhara Hiroyuki Ogawa Satoshi Nakatani Takahiro Ozutsumi Erika Shioyama Masaaki Yoshikawa Shigehiko Ueda Internal Medicine Kokuho Central Hospital 404-1MiyakoTawaramoto-choShiki-gunNara Prefecture 636-0302Japan

Aim: The development of hepatocellular carcinoma (HCC) is reduced after interferon based treatment in patients with chronic hepatitis C (CHC). A new therapy using direct-acting antiviral agents (DAA) has been widely applied since 2014 for CHC. The purpose of this study is to investigate the efficacy, safety and development of HCC after DAA treatment. Methods: The authors enrolled 33 consecutive patients who were treated with DAA for CHC at the hospital between January 2015 and March 2016. The laboratory data were collected at the start and 24 weeks after DAA therapy. Results: The authors analyzed 33 patients (18 male, 15 female, mean age of 68-year-old). The hepatic C virus genotypes were type 1 (27 patients) and type 2 (6 patients). The number of patients treated with sofosbuvir (SOF) +ledipasvir, daclatasvir + asunaprevir and SOF + ribavirin was 14, 13 and 6, respectively. The sustained virological response (SVR24) rate was 100%. Aspartate aminotransferase, alanine aminotransferase and FIB4-index were significantly decreased after SVR24. Adverse effects were observed in 9 patients (anemia, 5;liver function test disorder, 2;sarcoidosis, 1;pruritus, 1). With regard to HCC development, one elderly patient (3.0%) had multiple HCC recurrence after SVR24. Conclusion: DAA therapy achieved a high SVR24 rate with a good serological response. However, one patient had multiple HCC recurrence. These findings indicate that careful follow-up may be essential after DAA therapy.

关键词： Chronic hepatitis C direct-acting antiviral therapy development of hepatocellular carcinoma sarcoidosis

DNA methylation of angiotensin Ⅱ receptor gene in nonalcoholic steatohepatitis-related liver fibrosis

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World Journal of Hepatology 2016年第28期8卷 1194-1199页

作者： Kiyoshi Asada Yosuke Aihara Hiroaki Takaya Ryuichi Noguchi Tadashi Namisaki Kei Moriya Masakazu Uejima Mitsuteru Kitade Tsuyoshi Mashitani Kosuke Takeda Hideto Kawaratani Yasushi Okura Kosuke Kaji akitoshi douhara Yasuhiko Sawada Norihisa Nishimura Kenichiro Seki Akira Mitoro Junichi Yamao Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University

AIM To clarify whether Agtr1 a methylation is involved in the development of nonalcoholic steatohepatitis(NASH)-related liver fibrosis in adult *** A choline-deficient amino acid(CDAA) diet model was employed for methylation analysis of NASH-related liver ***1 a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid(CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific *** stellate cells(HSCs) were isolated by collagenase digestion of the liver,followed by centrifugation of the crude cell suspension through a density ***1 a methylation and its gene expression were also analyzed during the activation of *** The mean levels of Agtr1 a methylation in the livers of CDAA-fed rats(11.5% and 18.6% at 8 and 12 wk,respectively) tended to be higher(P = 0.06 and 0.09,respectively) than those in the livers of CSAA-fed rats(2.1% and 5.3% at 8 and 12 wk,respectively).Agtr1 a was not methylated at all in quiescent HSCs,but was clearly methylated in activated HSCs(13.8%,P < 0.01).Interestingly,although Agtr1 a was hypermethylated,the Agtr1 a m RNA level increased up to 2.2-fold(P < 0.05) in activated HSCs compared with that in quiescent HSCs,suggesting that Agtr1 a methylation did not silence its expression but instead had the potential to upregulate its *** findings indicate that Agtr1 a methylation and its upregulation of gene expression are associated with the development of NASH-related liver *** This is the first study to show that DNA methylation is potential y involved in the regulation of a renin-angiotensin system-related gene expression during liver fibrosis.

关键词： Epigenetics DNA methylation Angiotensin Ⅱ receptor Liver fibrosis Nonalcoholic steatohepatitis

Psychosis symptoms following aberrant immunity in the brain

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Neural Regeneration Research 2021年第3期16卷 512-513页

作者： akitoshi Ozaki Yuki Yamawaki Gen Ohtsuki Department of Biophysics Kyoto University Graduate School of ScienceKyotoJapan The Hakubi Center for Advanced Research Kyoto UniversityKyotoJapan Department of Drug Discovery Medicine Kyoto University Graduate School of MedicineKyotoJapan

Neuroinflammation in the brain is thought related to the emergence of various psychoses,although the identifying regional significance,the involvement of immune-cells and lymphocytic activity,and ways for the therapeutic recovery are under the effort of *** recently revealed that the cerebellar acute inflammation causes the symptoms manifested in mood disorders or developmental disorders,which were associated with hyperexcitability due to immune-triggered plasticity and the overconnectivity between the inflamed cerebellum and prefrontal cortex(Yamamoto et al.,2019).

关键词： inflammation immunity involvement

Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy:Report of a case and a review of the literature

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World Journal of Gastroenterology 2008年第1期14卷 132-135页

作者： Kenichi Hakamada Takuya Miura akitoshi Kimura Masaki Nara Yoshikazu Toyoki Shunij Narumi Mutsuo Sasak Department of Gastroenterological Surgery Hirosaki University Graduate School of Medicine Hirosaki 036-8562 Japan

Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology.

关键词： Mucinous cystic neoplasm Anaplastic carcinoma Pancreatic tumor Ovarian-like stroma Pregnancy

Propensity score matching analysis for clinical impact of braided-type versus laser-cut-type covered self-expandable metal stents for endoscopic ultrasound-guided hepaticogastrostomy

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 181-185页

作者： Mitsuki Tomita Takeshi Ogura akitoshi Hakoda Saori Ueno Atsushi Okuda Nobu Nishioka Yoshitaro Yamamoto Hiroki Nishikawa 2nd Department of Internal Medicine Osaka Medical and Pharmaceutical UniversityOsakaJapan Endoscopy Center Osaka Medical and Pharmaceutical UniversityOsakaJapan

Background:To prevent stent migration during endoscopic ultrasound-guided hepaticogastrostomy(EUS-HGS),intra-scope channel release technique is important,but is unfamiliar to non-expert *** self-expandable metal stent(SEMS)is an additional factor to prevent stent ***,no compara-tive studies of laser-cut-type and braided-type during EUS-HGS have been *** aim of this study was to compare the distance between the intrahepatic bile duct and stomach wall after EUS-HGS among laser-cut-type and braided-type ***:To evaluate stent anchoring function,we measured the distance between the hepatic parenchyma and stomach wall before EUS-HGS,one day after EUS-HGS,and 7 days after ***,propensity score matching was performed to create a propensity score for using laser-cut-type group and braided-type ***:A total of 142 patients were enrolled in this *** them,24 patients underwent EUS-HGS using a laser-cut-type SEMS,and 118 patients underwent EUS-HGS using a braided-type ***-HGS using the laser-cut-type SEMS was mainly performed by non-expert endoscopists(n=21);EUS-HGS using braided-type SEMS was mainly performed by expert endoscopists(n=98).The distance after 1 day was significantly shorter in the laser-cut-type group than that in the braided-type group[2.00(1.70-3.75)vs.6.90(3.72-11.70)mm,P<0.001].In addition,this distance remained significantly shorter in the laser-cut-type group after 7 *** these results were similar after propensity score matching analysis,the distance between hepatic parenchyma and stomach after 7 days was increased by 4 mm compared with the distance after 1 day in the braided-type *** the other hand,in the laser-cut-type group,the distance after 1 day and 7 days was almost the ***:EUS-HGS using a laser-cut-type SEMS may be safe to prevent stent migration,even in non-expert hands.

关键词： Endoscopic ultrasound-guided hepaticogastrostomy Endoscopic ultrasound-guided biliary drainage Endoscopic retrograde cholangiopancreatography

0.025-inch vs 0.035-inch guide wires for wire-guided cannulation during endoscopic retrograde cholangio pancreatography:A randomized study

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World Journal of Gastroenterology 2015年第30期21卷 9182-9188页

作者： Katsuya Kitamura Akira Yamamiya Yu Ishii Yoshiki Sato Tomoyuki Iwata Tomohiro Nomoto akitoshi Ikegami Hitoshi Yoshida Division of Gastroenterology Department of MedicineShowa University School of Medicine

AIM:To compare the clinical outcomes between 0.025-inch and 0.035-inch guide wires(GWs) when used in wire-guided cannulation(WGC).METHODS:A single center,randomized study was conducted between April 2011 and March 2013. This study was approved by the Medical Ethics Committee at our hospital. Informed,written consent was obtained from each patient prior to study enrollment. Three hundred and twenty-two patients with a na?ve papilla of Vater who underwent endoscopic retrograde cholangiopancreatography(ERCP) for the purpose of selective bile duct cannulation with WGC were enrolled in this study. Fifty-three patients were excluded based on the exclusion criteria,and 269 patients were randomly allocated to two groups by a computer and analyzed:the 0.025-inch GW group(n = 109) and the 0.035-inch GW group(n = 160). The primary endpoint was the success rate of selective bile duct cannulation with WGC. Secondary endpoints were the success rates of the pancreatic GW technique and precutting,selective bile duct cannulation time,ERCP procedure time,the rate of pancreatic duct stent placement,the final success rate of selective bile duct cannulation,andthe incidence of post-ERCP pancreatitis(PEP).RESULTS:The primary success rates of selective bile duct cannulation with WGC were 80.7%(88/109) and 86.3%(138/160) for the 0.025-inch and the 0.035-inch groups,respectively(P = 0.226). There were no statistically significant differences in the success rates of selective bile duct cannulation using the pancreatic duct GW technique(46.7% vs 52.4% for the 0.025-inch and 0.035-inch groups,respectively; P = 0.884) or in the success rates of selective bile duct cannulation using precutting(66.7% vs 63.6% for the 0.025-inch and 0.035-inch groups,respectively; P = 0.893). The final success rates for selective bile duct cannulation using these procedures were 92.7%(101/109) and 97.5%(156/160) for the 0.025-inch and 0.035-inch groups,respectively(P = 0.113). There were no significant differences

关键词： Endoscopic retrograde cholangiopancreatography Guide wire Post-endoscopic retrogradecholangiopancreatography pancreatitis Selective bileduct cannulation Wire-guided cannulation

Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation

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International Journal of Ophthalmology(English edition) 2022年第3期15卷 388-393页

作者： Koichi Yoshida Motofumi Kawai Tsugiaki Utsunomiya Akihiro Ishibazawa Young-Seok Song Mariana Sayuri BUdo Yoshikazu Tasaki akitoshi Yoshida Department of Ophthalmology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan Department of Hospital Pharmacy&Pharmacology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan

AIM: To investigate changes in extracellular matrix(ECM) gene expression in human trabecular meshwork(HTM) cells in response to mechanical fluid flow ***: HTM cells were grown on a glass plate coated with 0.02% type Ⅰ collagen(COL) and exposed to shear stress(0, 0.2, 1.0 dyne/cm;) for 12 *** in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain *** of Smad2 protein was investigated by Western ***: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control(P<0.05, <0.05, and <0.01, respectively).The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control(P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not *** phosphorylation of Smad2 levels was significantly higher compared to the static control ***: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical *** mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

关键词： trabecular meshwork shear stress aqueous humor extracellular matrix glaucoma intraocular pressure

Association of Omega-3 Polyunsaturated Fatty Acids with Sarcopenia in Liver Cirrhosis Patients with Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 613-624页

作者： akitoshi Sano Jun Inoue Eiji Kakazu Masashi Ninomiya Mio Tsuruoka Kosuke Sato Masazumi Onuki Satoko Sawahashi Keishi Ouchi Atsushi Masamune Division of Gastroenterology Tohoku University Graduate School of MedicineSendaiMiyagiJapan Department of Liver Disease The Research Center for Hepatitis and ImmunologyNational Center for Global Health and MedicineIchikawaChibaJapan

Background and Aims:Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma(HCC).Given their diverse physiological activities,we hypothesized that plasma fatty acids might influence the progression of *** study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with ***:In this singlecenter retrospective study,we registered 516 cases and analyzed 414 cases of liver cirrhosis and *** skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar *** cutoff value for sarcopenia followed the criteria set by the Japan Society of *** acid concentrations were measured by gas ***:Fatty acid levels,particularly omega-3(n-3)polyunsaturated fatty acid(PUFA),were lower in patients with poor liver function(Child-Pugh grade B/C)and were negatively correlated with the albumin-bilirubin score(p<0.0001).The prognosis of HCC patients with low PUFA levels was significantly *** the different fatty acid fractions,only n-3 PUFAs significantly correlated with skeletal muscle mass index(p=0.0026).In the multivariate analysis,the n-3 PUFA level was an independent variable associated with sarcopenia(p=0.0006).Conclusions:A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

关键词： Liver cirrhosis Hepatocellular carcinoma Sarcopenia Skeletal Muscle Fatty Acids Omega-3 polyunsaturated fatty acids

Registration of Two Dental Panoramic Radiographs

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Open Journal of Medical Imaging 2014年第1期4卷 4-13页

作者： Koichi Ogawa Jyunpei Yamamoto Masatoshi Yanase akitoshi Katsumata 2Department of Oral Radiology Asahi University School of Dentistry Gifu Japan Department of Applied Informatics Faculty of Science and Engineering Hosei University Tokyo Japan

In dental panoramic images, the information on physical changes of alveolar bone or jaw bone is very important to diagnose several diseases. To detect such change, it is useful to compare two panoramic x-ray images acquired at different times. These two images are usually acquired with different conditions in terms of the positioning of the dental arch, and thus these images can be impaired from some geometrical changes related to the scale of the panoramic images and deformation of the teeth and jaw bones. As a result of this, it is very hard to make an accurate registration. To cope with this issue, we developed a dedicated image registration method to match these two images by a newly introduced non-rigid transformation method and registration method using the cross-correlation of localized regions. We evaluated our proposed method with several sets of two images acquired with different geometrical conditions. The material evaluated in this study was a skull phantom. The results of these experiments showed the validity and intrinsic ability of our proposed method in clinical examinations.

关键词： Dental Panoramic Radiography Registration Quantitative Analysis Temporal Image Processing