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Search Results: 1 - 10 of 1088 matches for " Shinji Uemoto "
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Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications
Shinji Uemoto,Kazue Ozawa,Hiroto Egawa,Yasutsugu Takada
Clinical and Developmental Immunology , 2008, DOI: 10.1155/2008/718386
Abstract: To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication.
Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver
Takayuki Takeichi, Shinji Uemoto, Sachiko Minamiguchi, Izumi Takeyoshi, Yukihiro Inomata, Koichi Tanaka, Eiji Kobayashi
World Journal of Gastroenterology , 2009,
Abstract: AIM: To investigate the effects of a novel Leukotriene B4 receptor antagonist and/or tacrolimus on ischemia-reperfusion in a rat liver model.METHODS: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus), group 4 (ONO-4057 + tacrolimus).RESULTS: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more significantly in ONO-4057 plus tacrolimus group (P < 0.01), than in the tacrolimus alone group (P < 0.05), compared to controls.CONCLUSION: This study demonstrated that pretreatment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver ischemia-reperfusion injury.
Spontaneous necrosis of solid gallbladder adenocarcinoma accompanied with pancreaticobiliary maljunction
Tomohide Hori, Takashi Wagata, Kenji Takemoto, Takanobu Shigeta, Haruko Takuwa, Koichiro Hata, Shinji Uemoto, Naoki Yokoo
World Journal of Gastroenterology , 2008,
Abstract: A 71-year-old Japanese man with acute cholecystitis and an incarcerated gallbladder (GB) stone was admitted. Plain ultrasonography (US) incidentally detected a mass-like lesion in the fundus. Doppler US revealed that this elevated lesion had no blood flow. Computed tomography showed a relatively low-density mass, measuring 5 cm x 4 cm in diameter, with no positive enhancement. Magnetic resonance imaging showed a mass in the fundus with a slightly low intensity on T1-weighted images and a slightly high intensity on T2-weighted images. We were agonized in making the qualitative diagnosis of mass-like lesions of the fundus, such as a benign tumor, cancer, or debris. We performed laparoscopic cholecystectomy, because the incarcerated GB stone clearly caused acute cholecystitis. Intra-operative cholangiography clearly revealed pancreaticobiliary maljunction. Amylase levels in the common bile duct and gallbladder were quite high. The elevated lesion in the fundus clearly showed severe necrosis. Although this necrotic nodule included non-viable adenocarcinoma cells, viable cancer cell nests were located in the muscularis propria and subcutaneous layer. Histopathological examination confirmed a solid adenocarcinoma. Thus, we diagnosed it as a gallbladder cancer, based on histopathological analysis of the resected specimen. We therefore undertook radical surgery, including wedge resection of the liver, radical dissection of regional lymph nodes, and resection of the extrahepatic bile duct. Histopathological findings revealed no cancer, hyperplasia or dysplasia in the additionally resected specimens. The patient was finally staged as T2, N0, H0, P0, M(-), stage II. We present the first case of spontaneous necrosis of solid gallbladder adenocarcinoma, with a review of previous studies.
MicroRNA Profile Predicts Recurrence after Resection in Patients with Hepatocellular Carcinoma within the Milan Criteria
Fumiaki Sato,Etsuro Hatano,Koji Kitamura,Akira Myomoto,Takeshi Fujiwara,Satoko Takizawa,Soken Tsuchiya,Gozoh Tsujimoto,Shinji Uemoto,Kazuharu Shimizu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016435
Abstract: Hepatocellular carcinoma (HCC) is difficult to manage due to the high frequency of post-surgical recurrence. Early detection of the HCC recurrence after liver resection is important in making further therapeutic options, such as salvage liver transplantation. In this study, we utilized microRNA expression profiling to assess the risk of HCC recurrence after liver resection.
Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Hepatic Ischemia Reperfusion Injury in a Rat Model
Hiroyuki Kanazawa,Yasuhiro Fujimoto,Takumi Teratani,Junji Iwasaki,Naoya Kasahara,Kouji Negishi,Tatsuaki Tsuruyama,Shinji Uemoto,Eiji Kobayashi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019195
Abstract: Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy.
Pretreatment of Small-for-Size Grafts In Vivo by γ-Aminobutyric Acid Receptor Regulation against Oxidative Stress-Induced Injury in Rat Split Orthotopic Liver Transplantation
Tomohide Hori,Shinji Uemoto,Lindsay B. Walden,Feng Chen,Ann-Marie T. Baine,Toshiyuki Hata,Justin H. Nguyen
International Journal of Hepatology , 2013, DOI: 10.1155/2013/149123
Abstract: Background. Graft pretreatment to limit postoperative damage has the advantage of overcoming a current issue in liver transplantation (LT). The strategic potential of graft pretreatment in vivo by a specific agonist for γ-aminobutyric acid receptor (GABAR) was investigated in the rat LT model with a small-for-size graft (SFSG). Methods. Recipient rats were divided into three groups according to donor treatments and recipient surgeries: (i) saline and laparotomy, (ii) saline and split orthotopic liver transplantation (SOLT) with 40%-SFSG, and (iii) GABAR agonist and SOLT with 40%-SFSG. Survival was evaluated. Blood and liver samples were collected 6?h after surgery. Immunohistological assessment for apoptotic induction and western blotting for 4-hydroxynonenal, ataxia-telangiectasia mutated kinase (ATM), histone H2AX, phosphatidylinositol-3 kinase (PI3K), Akt, and free radical scavenging enzymes were performed. Results. Pretreatment by GABAR showed improvement in survival, histopathological assessment, and biochemical tests. Apoptotic induction and oxidative stress were observed after SOLT with an SFSG, and this damage was limited by GABAR regulation. GABAR regulation appeared to reduce DNA damage via the ATM/H2AX pathway and to promote cell survival via the PI3K/Akt pathway. Conclusions. Pretreatment in vivo by GABAR regulation improves graft damage after SOLT with an SFSG. This strategy may be advantageous in LT. 1. Introduction Oxygen is required for cell survival. However, oxygen also poses a potential hazard via reactive oxygen species (ROS) and reactive nitrogen species (RNS), with biological and functional alterations of lipids, proteins, and deoxyribonucleic acid (DNA) [1–3]. Therefore, ROS/RNS have been initially considered as harmful products of the normal aerobic metabolism. The control of ROS/RNS production plays physiological roles, especially, in regulating cell signaling to involve cell proliferation, differentiation, and apoptosis [1–3]. Oxidative stress (OS) mediated by free radicals is defined as an imbalance between the production of ROS/RNS and the antioxidant capacity of the cell [1–3]. These antioxidants ensure a defense against ROS/RNS-induced OS [2]. The predominant inhibitory neurotransmitter in the brain is γ-aminobutyric acid (GABA), and almost all researchers have focused on GABA or the regulation of GABA receptor (GABAR) in the brain [4–8]. Currently, GABA is considered to be a multifunctional molecule with various physiological effects throughout the body [9, 10]. In the brain, many researchers have found that the regulation
Dynamics of Hepatitis B Virus Quasispecies in Association with Nucleos(t)ide Analogue Treatment Determined by Ultra-Deep Sequencing
Norihiro Nishijima, Hiroyuki Marusawa, Yoshihide Ueda, Ken Takahashi, Akihiro Nasu, Yukio Osaki, Tadayuki Kou, Shujiro Yazumi, Takeshi Fujiwara, Soken Tsuchiya, Kazuharu Shimizu, Shinji Uemoto, Tsutomu Chiba
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035052
Abstract: Background and Aims Although the advent of ultra-deep sequencing technology allows for the analysis of heretofore-undetectable minor viral mutants, a limited amount of information is currently available regarding the clinical implications of hepatitis B virus (HBV) genomic heterogeneity. Methods To characterize the HBV genetic heterogeneity in association with anti-viral therapy, we performed ultra-deep sequencing of full-genome HBV in the liver and serum of 19 patients with chronic viral infection, including 14 therapy-na?ve and 5 nucleos(t)ide analogue(NA)-treated cases. Results Most genomic changes observed in viral variants were single base substitutions and were widely distributed throughout the HBV genome. Four of eight (50%) chronic therapy-na?ve HBeAg-negative patients showed a relatively low prevalence of the G1896A pre-core (pre-C) mutant in the liver tissues, suggesting that other mutations were involved in their HBeAg seroconversion. Interestingly, liver tissues in 4 of 5 (80%) of the chronic NA-treated anti-HBe-positive cases had extremely low levels of the G1896A pre-C mutant (0.0%, 0.0%, 0.1%, and 1.1%), suggesting the high sensitivity of the G1896A pre-C mutant to NA. Moreover, various abundances of clones resistant to NA were common in both the liver and serum of treatment-na?ve patients, and the proportion of M204VI mutants resistant to lamivudine and entecavir expanded in response to entecavir treatment in the serum of 35.7% (5/14) of patients, suggesting the putative risk of developing drug resistance to NA. Conclusion Our findings illustrate the strong advantage of deep sequencing on viral genome as a tool for dissecting the pathophysiology of HBV infection.
Prognostic value of metastin expression in human pancreatic cancer
Kazuyuki Nagai, Ryuichiro Doi, Fumihiko Katagiri, Tatsuo Ito, Atsushi Kida, Masayuki Koizumi, Toshihiko Masui, Yoshiya Kawaguchi, Kenji Tomita, Shinya Oishi, Nobutaka Fujii, Shinji Uemoto
Journal of Experimental & Clinical Cancer Research , 2009, DOI: 10.1186/1756-9966-28-9
Abstract: We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay.Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%), while strong expression of GPR54 was detected in 30 tumors (56.6%). Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047). Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04). Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02). Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03), and the patients with a high plasma metastin level (n = 6) did not die after surgical resection.Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.Pancreatic cancer remains a lethal disease and is the fourth to fifth leading cause of cancer-related death in the Western world, despite a significant reduction of the postoperative morbidity and mortality associated with pancreatectomy[1,2]. While surgical resection represents the only definitive option for cure of this disease and complete tumor resection is associated with longer survival, only 10% to 15% of p
Midkine promoter-based conditionally replicative adenovirus therapy for midkine-expressing human pancreatic cancer
Eiji Toyoda, Ryuichiro Doi, Kazuhiro Kami, Tomohiko Mori, Daisuke Ito, Masayuki Koizumi, Atsushi Kida, Kazuyuki Nagai, Tatsuo Ito, Toshihiko Masui, Michihiko Wada, Masatoshi Tagawa, Shinji Uemoto
Journal of Experimental & Clinical Cancer Research , 2008, DOI: 10.1186/1756-9966-27-30
Abstract: We examined midkine mRNA expression and midkine protein expression by seven human pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, MIAPaCa-2, PANC-1, and Suit-2), as well as by non-cancerous pancreatic tissue and pancreatic cancers. Midkine promoter activity was measured in cancer cell lines by the dual luciferase reporter assay. Adenoviral transduction efficiency was assessed by fluorescent staining of cancer cell lines using adenovirus type 5 containing the green fluorescent protein gene (Ad5GFP). Replication of adenovirus type 5 containing the 0.6 kb midkne promoter (Ad5MK) was assessed by the detection of E1 protein in cancer cell lines. The cytotoxicity of Ad5MK for cancer cells was evaluated from the extent of growth inhibition after viral infection. Infection and replication were also assessed in nude mice with subcutaneous Suit-2 tumors by intratumoral injection of Ad5MK, Ad5GFP, or vehicle. E1a mRNA expression in the treated tumors and expression of the replication-specific adenoviral hexon protein were evaluated. Finally, the anti-tumor activity of Ad5MK against intraperitoneal xenografts of Suit-2 pancreatic cancer cells was examined after intraperitoneal injection of the virus.Both midkine mRNA expression and midkine protein expression were strong in AsPC-1 and CFPAC-1 cell liens, moderate in BxPC-3, HPAC, and Suit-2 cell lines, and weak in PANC-1 and MIAPaCa-2 cell lines. Expression of midkine mRNA was significantly stronger in pancreatic cancers than in non-cancerous pancreatic tissues. The relative luciferase activity mediated by the 0.6 kb midkne fragment in AsPC-1, PANC-1, and Suit-2 cell lines was approximately 6 to 20 times greater than that in midkne-negative MIAPaCa-2 cell lines. Pancreatic cancer cell lines exhibited a heterogeneous adenoviral transduction profile. E1A expression was higher in cell lines with strong midkine expression than in cell lines with weak midkine expression. Ad5MK showed much greater cytotoxicity for midkine
Predictive Factors for Reintubation following Noninvasive Ventilation in Patients with Respiratory Complications after Living Donor Liver Transplantation
Yuichi Chihara, Hiroto Egawa, Toru Oga, Tomomasa Tsuboi, Tomohiro Handa, Shintaro Yagi, Taku Iida, Atsushi Yoshizawa, Kazuhiko Yamamoto, Michiaki Mishima, Koichi Tanaka, Shinji Uemoto, Kazuo Chin
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081417
Abstract: Background Postoperative respiratory complications are a major cause of mortality following liver transplantation (LT). Noninvasive ventilation (NIV) appears to be effective for respiratory complications in patients undergoing solid organ transplantation; however, mortality has been high in patients who experienced reintubation in spite of NIV therapy. The predictors of reintubation following NIV therapy after LT are not exactly known. Methods Of 511 adult patients who received living-donor LT, data on the 179 who were treated by NIV were retrospectively examined. Results Forty-three (24%) of the 179 patients who received NIV treatment required reintubation. Independent factors associated with reintubation by multivariate logistic regression analysis were controlled preoperative infections (odds ratio [OR] 8.88; 95% confidence interval (CI) 1.64 to 48.11; p = 0.01), ABO-incompatibility (OR 4.49; 95% CI, 1.50 to 13.38; p = 0.007), and presence of postoperative pneumonia at the time of starting NIV (OR 3.28; 95% CI, 1.02 to 11.01; p = 0.04). The reintubated patients had a significant higher rate of postoperative infectious complications and a significantly longer intensive care unit stay than those in whom NIV was successful (p<0.0001). Of the 43 reintubated patients, 22 (51.2%) died during hospitalization following LT vs. 8 (5.9%) of the 136 patients in whom NIV was successful (p<0.0001). Conclusions Because controlled preoperative infection, ABO-incompatibility or pneumonia prior to the start of NIV were independent risk factors for reintubation following NIV, caution should be used in applying NIV in patients with these conditions considering the high rate of mortality in patients requiring reintubation following NIV.
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