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      • KCI등재

        Ceramide/Sphingomyelin Rheostat Regulated by Sphingomyelin Synthases and Chronic Diseases in Murine Models

        Makoto Taniguchi,Toshiro Okazaki 한국지질동맥경화학회 2020 지질·동맥경화학회지 Vol.9 No.3

        Ceramide and sphingomyelin (SM) are major components of the double membrane-bound sphingolipids. Ceramide is an essential bioactive lipid involved in numerous cell processes including apoptosis, necrosis, and autophagy-dependent cell death. Inversely, SM regulates opposite cellular processes such as proliferation and migration by changing receptor-mediated signal transduction in the lipid microdomain. SM is generated through a transfer of phosphocholine from phosphatidylcholine to ceramide by SM synthases (SMSs). Research during the past several decades has revealed that the ceramide/SM balance in cellular membranes regulated by SMSs is important to decide the cell fate, survival, and proliferation. In addition, recent experimental studies utilizing SMS knockout mice and murine disease models provide evidence that SMS-regulated ceramide/SM balance is involved in human diseases. Here, we review the basic structural and functional characteristics of SMSs and focus on their cellular functions through the regulation of ceramide/SM balance in membrane microdomains. In addition, we present the pathological or physiological implications of SMSs by analyzing their role in SMS-knockout mice and human disease models. This review finally presents evidence indicating that the regulation of ceramide/SM balance through SMS could be a therapeutic target for human disorders.

      • KCI등재

        Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies

        Kitatani, Kazuyuki,Taniguchi, Makoto,Okazaki, Toshiro Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.6

        Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

      • KCI등재

        Complications of Spine Surgery in Elderly Japanese Patients: Implications for Future of World Population Aging

        Motoyuki Umekawa,Keisuke Takai,Makoto Taniguchi 대한척추신경외과학회 2019 대한척추신경외과학회지 Vol.16 No.4

        Objective: To analyze the relationship between age and perioperative complications of spine surgery in a Japanese cohort with the longest average life expectancy in the world. Methods: Patients with spinal stenosis who underwent standard spine surgery without instrumented fusion were divided into 4 groups: adults (20–64 years), the young-old (65–74), the middle old (75–84), and the oldest-old (≥85). Data on medical complications, surgical complications, and deaths within 30 days of index surgery were compared across the groups. Risk factors for complications were identified through multivariate analysis. Results: A total of 584 patients underwent 673 operations: 35% were performed on adult patients, 33% on the young-old, 27% on the middle old, and 5% on the oldest-old. The rates of total or [major] medical complications significantly increased with age (8% [0.8%], 11% [0.9%], 27% [3.9%], 45% [9.1%], respectively; p<0.001 [p=0.003]), whereas those of surgical complications did not differ (11%, 8.1%, 14%, 9.1%, respectively; p=0.25). Independent risk factors for medical complications were an age of 75 years or older (75–84: odds ratio [OR], 5.1; ≥85: OR, 6.2) and American Society of Anesthesiologists (ASA) physical status classification III (OR, 5.4). Two patients older than 85 years died from medical complications. Conclusion: The complications of spine surgery increased in the middle and oldest-old patients because of medical complications; however, most were minor and treatable. Major complications were associated with preoperative medical comorbidities and their severities; therefore, most elderly patients with low ASA physical status classification (≤II) may benefit from spine surgery.

      • KCI등재

        Nonrheumatoid Retro-Odontoid Pseudotumors: Characteristics, Surgical Outcomes, and Time-Dependent Regression After Posterior Fixation

        Ryoko Niwa,Keisuke Takai,Makoto Taniguchi 대한척추신경외과학회 2021 Neurospine Vol.18 No.1

        Objective: Although a retro-odontoid pseudotumor associated with rheumatoid arthritis is a well-known clinical entity, little is known about retro-odontoid pseudotumors not associated with rheumatoid arthritis due to their rarity. Methods: Between 2006 and 2019, consecutive patients with nonrheumatoid pseudotumors were included and retrospectively compared with patients with rheumatoid pseudotumors. Results: Nineteen patients had nonrheumatoid pseudotumors (mean age, 73±6 years; male, 53%). All had cervical lesions including ossified anterior and posterior longitudinal ligaments with a history of cervical surgery in 5. The mean thickness of the pseudotumors at diagnosis was 8.1 mm (range, 4.2–17.2 mm). Pseudotumor thickness had a significant negative correlation with the atlantodental interval (p=0.008) and the subaxial range of motion (p=0.049). In comparison with 7 rheumatoid pseudotumor patients, nonrheumatoid pseudotumor patients were older (p=0.042), had a higher proportion of males (p=0.023), had a smaller atlantodental interval (p=0.007), and had larger pseudotumors at diagnosis (p=0.030). Of the 19 patients, 18 received posterior fixation with or without C1 laminectomy, while the other received C1 laminectomy alone. The percent pseudotumor thickness at follow-up to those at diagnosis was 91%, 77%, 68%, 46%, 58%, and 49% at 1, 3, 6, 12, 24, and 36 months after surgery, respectively. Conclusion: This study revealed markedly clinical and radiological differences between nonrheumatoid and rheumatoid pseudotumors. The main etiology for nonrheumatoid pseudotumors was subaxial cervical degeneration and ossified lesions. There were good outcomes following posterior fixation and time-dependent pseudotumor regression within 12 months.

      • KCI등재

        Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies

        Kazuyuki Kitatani,Toshiro Okazaki,Makoto Taniguchi 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.6

        Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1- phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

      • A Massively Parallel Circuit Simulator for Power Grids Analysis

        Hisako SUGANO,Yuuya ISODA,Makoto YOKOTA,Ittetsu TANIGUCHI,Masaya YOSHIKAWA,Masahiro FUKUI 대한전자공학회 2009 ITC-CSCC :International Technical Conference on Ci Vol.2009 No.7

        With the shrinking of patterns in VLSIs, it becomes hard to neglect those problems related to IR-drop, electro migration, and so on. It takes huge calculation time to analyze and optimize these issues. The GPU computation is one of the expected approaches, since the innovation of the GPU is much faster than the CPU. The algorithm utilizes shared memories as much as possible to reduce to total computation time. The experimental results show that it achieves 15 times fast computation than CPU with similar accuracy.

      • KCI등재

        Effects of Furanocoumarins in Kampo Extract-Based Medicines on Rat Intestinal Absorption of CYP3A and P-glycoprotein Substrate Drugs In Vivo

        Kazunori Iwanaga,Kaori Arimune,Makoto Miyazaki,Makio Shibano,Masahiko Taniguchi,Kimiye Baba,Masawo Kakemi 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

        While a great deal of information of drug-drug interactions is known, most concern Western drugs. Relatively little is known of the interactions between Western drugs and traditional drugs such as Kampo extract medicines (Japanese medicines modified from traditional Chinese medicines). This study investigated the effects of the marketed Kampo extract medicines, Senkyu-cha-cho-san and Sokei-kakketsu-to, on the intestinal absorption of CYP or P-glycoprotein (P-gp) in vivo. Midazolam, a CYP3A substrate drug, or talinolol, a P-gp substrate drug, was orally administered to rats with each of these Kampo extract medicines. Senkyu-cha-chosan or Sokei-kakketsu-to administered as a standard regimen did not obviously affect Cmax and area under the curve (AUC) of midazolam, although both Kampo extract medicines contained notopterol, a potent CYP3A4 inhibitor in vitro. The results implied a lack of potent drug–drug interactions between both Kampo extract medicines and CYP3A substrate drugs. Concomitant administration of each Kampo extract medicine unexpectedly showed the tendency to decrease Cmax and AUC of talinolol. Decreased intestinal absorption of talinolol might be caused, not by the inhibition of P-gp, but by the inhibition of organic anion transporting peptides by both Kampo extract medicines.

      • Diagnostic Performance of Diffusion Weighted Imaging of Malignant and Benign Pulmonary Nodules and Masses: Comparison with Positron Emission Tomography

        Usuda, Katsuo,Sagawa, Motoyasu,Motono, Nozomu,Ueno, Masakatsu,Tanaka, Makoto,Machida, Yuichiro,Maeda, Sumiko,Matoba, Munetaka,Kuginuki, Yasuaki,Taniguchi, Mitsuru,Tonami, Hisao,Ueda, Yoshimichi,Sakuma Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

        Background: Diffusion-weighted imaging (DWI) makes it possible to detect malignant tumors based on the diffusion of water molecules. However, it is uncertain whether DWI has advantages over FDG-PET for distinguishing malignant from benign pulmonary nodules and masses. Materials and Methods: One hundred-forty-three lung cancers, 17 metastatic lung tumors, and 29 benign pulmonary nodules and masses were assessed in this study. DWI and FDG-PET were performed. Results: The apparent diffusion coefficient (ADC) value ($1.27{\pm}0.35{\times}10^{-3}mm^2/sec$) of malignant pulmonary nodules and masses was significantly lower than that ($1.66{\pm}0.58{\times}10^{-3}mm^2/sec$) of benign pulmonary nodules and masses. The maximum standardized uptake value (SUVmax: $7.47{\pm}6.10$) of malignant pulmonary nodules and masses were also significantly higher than that ($3.89{\pm}4.04$) of benign nodules and masses. By using optimal cutoff values for ADC ($1.44{\times}10^{-3}mm^2/sec$) and for SUVmax (3.43), which were determined with receiver operating characteristics curves (ROC curves), the sensitivity (80.0%) of DWI was significantly higher than that (70.0%) of FDG-PET. The specificity (65.5%) of DWI was equal to that (65.5%) of FDG-PET. The accuracy (77.8%) of DWI was not significantly higher than that (69.3%) of FDG-PET for pulmonary nodules and masses. As the percentage of bronchioloalveolar carcinoma (BAC) component in adenocarcinoma increased, the sensitivity of FDG-PET decreased. DWI could not help in the diagnosis of mucinous adenocarcinomas as malignant, and FDG-PET could help in the correct diagnosis of 5 out of 6 mucinous adenocarcinomas as malignant. Conclusions: DWI has higher potential than PET in assessing pulmonary nodules and masses. Both diagnostic approaches have their specific strengths and weaknesses which are determined by the underlying pathology of pulmonary nodules and masses.

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