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Satoshi Kawamura,Nobuyuki Horie,Noriko Okahashi,Hashihiro Higuchi 한국독성학회 2019 Toxicological Research Vol.35 No.4
Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.
Kawamura, Satoshi,Horie, Nobuyuki,Okahashi, Noriko,Higuchi, Hashihiro Korean Society of ToxicologyKorea Environmental Mu 2019 Toxicological Research Vol.35 No.4
Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.
Kawamura Satoshi,Karasawa Yuki,Toda Nobuo,Nakai Yousuke,Shibata Chikako,Kurokawa Ken,Arai Junya,Funato Kazuyoshi,Kurosaki Shigeyuki,Maeshima Shuya,Kondo Mayuko,Kojima Kentaro,Ohki Takamasa,Seki Michih 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.6
Background/Aims: Empiric antibiotics are given in combination with biliary drainage for acute cholangitis but sometimes turn out to be insensitive to microorganisms in blood and bile. Clinical outcomes were compared according to sensitivity to microorganisms detected in blood and bile culture to evaluate the impact of sensitivity to empiric antibiotics in cholangitis. Methods: Consecutive patients who underwent biliary drainage for acute cholangitis were retrospectively studied. Clinical outcomes such as 30-day mortality, length of hospital stay and high care unit stay, organ dysfunction and duration of fever were compared in three groups: group A (sensitive to both blood and bile culture), group B (sensitive to blood culture alone) and group C (insensitive to both blood and bile culture). Results: Eighty episodes of cholangitis were classified according to sensitivity results: 42, 32 and six in groups A, B and C. Escherichia coli and Klebsiella were two major pathogens. There were no significant differences in 30-day mortality rate (7%, 0%, and 0%, p=0.244), length of hospital stay (28.5, 21.0, and 20.5 days, p=0.369), organ dysfunction rate (14%, 25%, and 17%, p=0.500), duration of fever (4.3, 3.2, and 3.5 days, p=0.921) and length of high care unit stay (1.4, 1.2, and 1.7 days, p=0.070) in groups A, B and C. Empiric antibiotics were changed in 11 episodes but clinical outcomes appeared to be non-inferior even in 31 episodes of cholangitis who were on inadequate antibiotics throughout the course. Conclusions: Sensitivity of empiric antibiotics was not associated with clinical outcomes in acute cholangitis.
Fungemia due to Trichosporon dermatis in a patient with refractory Burkitt’s leukemia
Satoshi Hashino,Shojiro Takahashi,Rena Morita,Hiroe Kanamori,Masahiro Onozawa,Takahito Kawamura,Kaoru Kahata,Takeshi Kondo,Issei Tokimatsu,Takashi Sugita,Koji Akizawa,Masahiro Asaka 대한혈액학회 2013 Blood Research Vol.48 No.2
Fungemia due to Trichosporon dermatis in a patient with refractory Burkitt’s leukemia
Satoshi Hashino,Shojiro Takahashi,Rena Morita,Hiroe Kanamori,Masahiro Onozawa,Takahito Kawamura,Kaoru Kahata,Takeshi Kondo,Issei Tokimatsu,Takashi Sugita,Koji Akizawa,Masahiro Asaka 대한혈액학회 2013 Blood Research Vol.48 No.2
( Yusuke Kawamura ),( Kenji Ikeda ),( Taito Fukushima ),( Yuya Seko ),( Tasuku Hara ),( Hitomi Sezaki ),( Tetsuya Hosaka ),( Norio Akuta ),( Masahiro Kobayashi ),( Satoshi Saitoh ),( Fumitaka Suzuki ) The Editorial Office of Gut and Liver 2013 Gut and Liver Vol.7 No.5
Background/Aims: The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion thera-py for hepatocellular carcinoma (HCC). Methods: We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gela-tin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. Results: The mean free cisplatin concentrations were as fol-lows. For group A, the mean was 48.58 μg/mL at 0 minute, 7.31 mL at 5 minutes, 5.70 mL at 10 minutes, and 7.15 mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 μg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. Conclusions: These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver. (Gut Liver 2013;7:576-584)
( Tatsuya Hayashi ),( Satoshi Saitoh ),( Kei Fukuzawa ),( Yoshinori Tsuji ),( Junji Takahashi ),( Yusuke Kawamura ),( Norio Akuta ),( Masahiro Kobayashi ),( Kenji Ikeda ),( Takeshi Fujii ),( Tosiaki M 대한간학회 2017 Gut and Liver Vol.11 No.5
Background/Aims: Noninvasive liver fibrosis evaluation was performed in patients with nonalcoholic fatty liver disease (NAFLD). We used a quantitative method based on the he-patic volume acquired from gadoxetate disodium-enhanced (Gd-EOB-DTPA-enhanced) magnetic resonance imaging (MRI) for diagnosing advanced fibrosis in patients with NAFLD. Methods: A total of 130 patients who were diagnosed with NAFLD and underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. Histological data were available for 118 patients. Hepatic volumetric parameters, including the left hepatic lobe to right hepatic lobe volume ratio (L/R ratio), were measured. The usefulness of the L/R ratio for diag-nosing fibrosis ≥F3-4 and F4 was assessed using the area under the receiver operating characteristic (AUROC) curve. Multiple regression analysis was performed to identify vari-ables (age, body mass index, serum fibrosis markers, and histological features) that were associated with the L/R ratio. Results: The L/R ratio demonstrated good performance in differentiating advanced fibrosis (AUROC, 0.80; 95% confi-dence interval, 0.72 to 0.88) from cirrhosis (AUROC, 0.87; 95% confidence interval, 0.75 to 0.99). Multiple regression analysis showed that only fibrosis was significantly associat-ed with the L/R ratio (coefficient, 0.121; p<0.0001). Conclu-sions: The L/R ratio, which is not influenced by pathologi-cal parameters other than fibrosis, is useful for diagnosing cirrhosis in patients with NAFLD. (Gut Liver 2017;11:674- 683)
( Norio Akuta ),( Yusuke Kawamura ),( Yasuji Arase ),( Fumitaka Suzuki ),( Hitomi Sezaki ),( Tetsuya Hosaka ),( Masahiro Kobayashi ),( Mariko Kobayashi ),( Satoshi Saitoh ),( Yoshiyuki Suzuki ),( Kenj 대한간학회 2016 Gut and Liver Vol.10 No.3
Background/Aims: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. Methods: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. Results: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. Conclusions: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features. (Gut Liver 2016;10:437-445)
Yasukawa Taiki,Ohya Junichi,Kawamura Naohiro,Yoshida Yuichi,Onishi Yuki,Kohata Kazuhiro,Kakuta Yohei,Nagatani Satoshi,Kudo Yoshifumi,Shirahata Toshiyuki,Kunogi Junichi 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.5
Study Design: Clinical case series.Purpose: This study aimed to report dynamization–posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysisrelated spondyloarthropathy (HSA), and investigate patients’ postoperative course within 2 years.Overview of Literature: HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed “dynamization–PLIF” in hemodialysis patients with destructive vertebral endplate changes.Methods: We retrospectively examined patients with HSA who underwent dynamization–PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant.Results: We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization– PLIF (lumbar lordosis, 28.4°–35.5°; local lordosis, 2.7°–12.8°; <i>p</i><0.01). The mean local lordosis was maintained throughout the postoperative course at 1- and 2-year follow-up (12.9°–12.8°, p=0.89 and 12.9°–11.8°, <i>p</i>=0.07, respectively). Solid fusion was achieved in 59 (89%) of 66 fused segments. Solid fusion of all fixed segments was achieved in 42 cases (84%). Within 2 years postoperatively, only six cases (12%) were reoperated (two, surgical debridement for surgical site infection; two, reoperation for pedicle screw loosening; one, laminectomy for epidural hematoma; one, additional fusion for adjacent segment disease).Conclusions: Dynamization–PLIF showed local lordosis improvement, a high solid fusion rate, and a low reoperation rate within 2 years of follow-up.
Risk Factors for Acute Cholangitis Caused by Enterococcus faecalis and Enterococcus faecium
( Yuki Karasawa ),( Jun Kato ),( Satoshi Kawamura ),( Kentaro Kojima ),( Takamasa Ohki ),( Michiharu Seki ),( Kazumi ),( Tagawa ),( Nobuo Toda ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Gut and Liver Vol.15 No.4
Background/Aims: Acute cholangitis (AC) is a potentially life-threatening bacterial infection, and timely antimicrobial treatment, faster than that achieved with bacterial cultures, is recommended. Although the current guidelines refer to empirical antimicrobial treatment, various kinds of antimicrobial agents have been cited because of insufficient analyses on the spectrum of pathogens in AC. Enterococcus spp. is one of the most frequently isolated Gram-positive bacteria from the bile of patients with AC, but its risk factors have not been extensively studied. This study aimed to analyze the risk factors of AC caused by Enterococcus faecalis and Enterococcus faecium. Methods: Patients with AC who were hospitalized in a Japanese tertiary center between 2010 and 2015 were retrospectively analyzed. Patients’ first AC episodes in the hospital were evaluated. Results: A total of 266 patients with AC were identified. E. faecalis and/or E. faecium was isolated in 56 (21%) episodes of AC. Prior endoscopic sphincterotomy (EST), the presence of a biliary stent, prior cholecystectomy, and past intensive care unit admission were more frequently observed in AC patients with E. faecalis and/or E. faecium than in those without such bacteria. Prior EST was identified as an independent risk factor for AC caused by E. faecalis and/or E. faecium in the multivariate analysis. Conclusions: Given the intrinsic resistance of E. faecalis and E. faecium to antibiotics, clinicians should consider empirical therapy with anti-enterococcal antibiotics for patients with prior EST. (Gut Liver 2021;15:616-624)