Synthesis and biological evaluation of the mimics of cis ligand for CD22

Yuki Sugamuna,Naoko Matsubara,Yuki Iwayama,Akiharu Ueki,Akihiro Imamura,Hiromune Ando,Takeshi Tsubata,Hideharu Ishida,Makoto Kiso 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

CD22 (siglec-2) is an accessory molecule of the B-cell receptor complex (BCR) that exertsnegative effects on receptor signaling. It is also well-documented that CD22 is a regulatoryprotein that sets a threshold for immune responses. The carbohydrate ligand recognized byCD22 is the sequence Neuα(2,6)Galβ(1,4)GlcNAc found on both neighboringglycoconjugate of the same cell (cis ligand) and on other cells that interact with B cells (transligands). Recently, we have reported that the C-9 amido derivative of sialic acid (GSC718;9-(4’-hydroxy-4-biphenyl)acetamido-9-deoxy-Neu5Gc-OBn) show a potent affinity andselectivity for CD22 than other siglecs such as MAG [1]. Moreover, the compoundpromoted the proliferation of B cells in vitro. As next step of our investigation, we intend toreinforce the promoting activity of GSC718 for B cell growth by chemical modification.Herein, we report the efficient synthesis of GSC718 analogs which have varied aglyconmoieties. To achieve the comprehensive synthesis of GSC718 analogs having varied aglycons, wereexamined every synthetic process to obtain a fine target compound. In case of thesialoside synthesis, the most time-consuming and troublesome process is thechromatographic separation of α-sialoside from other byproducts such as β−isomer, 2,3-enederivative etc. after glycosylation reaction with aglycon part. To improve this process, weemployed 1,5-lactam formation as the key step for separation because the lactam formation isknown to proceed only in α-sialoside [2]. At the beginning of the synthesis of targetmolecules, we synthesized a suitably modified sialic acid donor in good yields. Then, thesialyl donor was reacted with various 2-substituted-ethanols to give the mixtures of α- and β-glycosides and 2,3-ene derivative, which were subsequently advanced to 1,5-lactamformation. As we anticipated, 1,5-lactamized α-sialosides became isolable from themixtures due to its different polarity from the other byproducts. Finally, the obtained 1,5-lactamized silaosides were successfully converted into target structures via reaction sequenceincluding C9-midification with biphenyl amide group, lactam opening and globaldeprotection. The synthesized analogs were advanced to biological assay using B cells. In this poster presentation, we will also discuss the structure-activity relationships of thesynthesized analogs. [1] H. H. M. Abdu-Allah et al, Bioorg. Med. Chem. Lett. 2011, 19, 1966-1971. [2] H. Tanaka et al, Tetrahedron Lett. 2009, 50, 4478-4481.

A Proposal of Refactoring toWell-StructuredWorkflow Nets

Yuki Kuroda,Shingo Yamaguchi,Minoru Tanaka 대한전자공학회 2009 ITC-CSCC :International Technical Conference on Ci Vol.2009 No.7

In this paper, we discuss refactoring free choice workflow nets (WF-net for short) to well-structured ones. It is known that most actual workflows can be modeled as free choice or well-strcutured WF-nets. There are more analysis methods for well-structured WF-nets. Refactoring free choice WF-nets to well-structured ones enables us to apply many analysis methods to free choice ones. We propose two rules for the refactoring. And we show an example of refactroing a WF-net, which represents the actual workflow for an travel agency.

Morphological Patterns of the Anterior Median Fissure in the Cervical Spinal Cord Evaluated by Computed Tomography After Myelography

Yuki Oichi,Junya Hanakita,Toshiyuki Takahashi,Manabu Minami,Taigo Kawaoka,Yusuke Funakoshi,Takeshi Kawauchi,Yasufumi Ohtake 대한척추신경외과학회 2018 Neurospine Vol.15 No.4

Objective: Computed tomography following myelography (CTM) revealed an unusual flow of contrast dye into the anterior median fissure (AMF) in a patient with cervical spondylotic myelopathy. Since then, several AMF configurations have been observed on CTM. Therefore, we evaluated morphological patterns of the AMF on CTM and investigated the significance and mechanisms of contrast dye flow into the AMF. Methods: Morphological patterns of the AMF on CTM were examined in 79 patients. Group A (24 patients) underwent surgery because of symptomatic cervical myelopathy. Group B (43 patients) had no clinical symptoms but showed spinal cord compression on CTM. Group C (12 patients), who showed neither clinical symptoms nor cord changes, underwent CTM for lumbar lesion evaluation. AMF patterns were classified into 4 types according to their configurations on CTM (reversed T, Y, V, and O types). Results: In group B, the reversed T type and Y type appeared significantly more often near the compressed portion (p<0.001). A similar tendency was seen in group A. The V and O types were most frequently observed in group C (p<0.001). Conclusion: On CTM, contrast dye tends to flow into the AMF of the cervical cord when the spinal cord is compressed. We speculate that there may be 3 possible mechanisms for this phenomenon: deformation of the epipial layer of the AMF due to cervical cord compression, AMF dilatation due to atrophy of the anterior funiculus or anterior horn, and temporary AMF dilatation when it becomes an alternative route for cerebrospinal fluid circulation.

The therapeutic effect of CD133⁺ cells derived from human umbilical cord blood on neonatal mouse hypoxic-ischemic encephalopathy model

( Yukie Kidani ),( Yasuo Miki ),( Nana Nomimura ),( Shiori Minakawa ),( Norifumi Tanaka ),( Hiroshi Miyoshi ),( Koichi Wakabayashi ),( Yoshiki Kudo ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

Objectives: Hypoxic-ischemic encephalopathy (HIE) is a major cause of cerebral palsy in full-term infants. HIE occurs at a rate of about three per thousand live-born infants, even in developed countries. In recent years stem cell therapies have been applied in several fields of medicine. Endothelial progenitor cells (EPCs) are one of the major stem/progenitor cell subsets with the potential for repairing vascular injury. Therefore, we have speculated that the transplantation of CD133⁺ cells, as a EPCs containing fraction, from umbilical cord blood could also be an useful therapy in perinatal hypoxia-induced brain injury. We established the ex vitro hypoxic-ischemic encephalopathy model to assess the effects of CD133⁺ cells (endothelial progenitor cells) derived from human umbilical cord blood on nerve extension. In this study, we have investigated the therapeutic effects of CD133⁺ cells for the treatment of neonatal HIE on an animal model. Methods: Hypoxic-ischemic brain lesions were induced in neonatal severe combined immunodeficiency mice using the Rice-Vanucci method. CD133⁺ cells were administered by intraperitoneal injection 24 h after injury. Macroscopic assessment, growth evaluation and immunohistochemical analysis were performed. To evaluate motor function, rotarod test was performed every 7days between day 28 and day 56 of postnatal. Results: Immunohistochemical analysis revealed that intraperitoneally transplanted CD133⁺ cells migrate towards the brain 48 h after injection. The ratio of lesioned to non-lesioned hemisphere area in the CD133⁺ group was significantly higher than in the HI group. Moreover, in CD133⁺ cell-treated animals, motor function improved and the brain was protected from the hypoxic-ischemic insult compared with untreated animals. Conclusion: Our results suggest that CD133⁺ cells derived from human umbilical cord blood have therapeutic po-tential in neonatal hypoxic-ischemic encephalopathy.

22-gauge Co-Cr versus stainless-steel Franseen needles for endoscopic ultrasound-guided tissue acquisition in patients with solid pancreatic lesions

Yuki Tanisaka,Masafumi Mizuide,Akashi Fujita,Ryuhei Jinushi,Rie Shiomi,Takahiro Shin,Kei Sugimoto,Tomoaki Tashima,Yumi Mashimo,Shomei Ryozawa 대한소화기내시경학회 2024 Clinical Endoscopy Vol.57 No.2

Background/Aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) using Franseen needles is reportedly useful for its high diagnostic yield. This study compared the diagnostic yield and puncturing ability of EUS-TA using 22-gauge cobalt-chromium (CO-Cr) needles with those of stainless-steel Franseen needles in patients with solid pancreatic lesions. Methods: Outcomes were compared between the 22-gauge Co-Cr Franseen needle (December 2019 to November 2020; group C) and stainless-steel needle (November 2020 to May 2022; group S). Results: A total of 155 patients (group C, 75; group S, 80) were eligible. The diagnostic accuracy was 92.0% in group C and 96.3% in group S with no significant intergroup differences (p=0.32). The rate of change in the operator (from training fellows to experts) was 20.0% (15/75) in group C and 7.5% (6/80) in group S. Stainless-steel Franseen needles showed less inter-operator difference than Co-Cr needles (p=0.03). Conclusions: Both Co-Cr and stainless-steel Franseen needles showed high diagnostic ability. Stainless-steel Franseen needles are soft and flexible; therefore, the range of puncture angles can be widely adjusted, making them suitable for training fellows to complete the procedure.

SAFETY OF THE SUPER LWR

YUKI ISHIWATARI 한국원자력학회 2007 Nuclear Engineering and Technology Vol.39 No.4

Supercritical water-cooled reactors (SCWRs) are recognized as a Generation IV reactor concept. The Super LWR is a pressure-vessel type thermal spectrum SCWR with downward-flow water rods and is currently under study at the University of Tokyo. This paper reviews Super LWR safety. The fundamental requirement for the Super LWR, which has a oncethrough coolant cycle, is the core coolant flow rate rather than the coolant inventory. Key safety characteristics of the Super LWR inhere in the design features and have been identified through a series of safety analyses. Although loss-of-flow is the most important abnormality, fuel rod heat-up is mitigated by the “heat sink” and “water source” effects of the water rods. Response of the reactor power against pressurization events is mild due to a small change in the average coolant density and flow stagnation of the once-through coolant cycle. These mild responses against transients and also reactivity feedbacks provide good inherent safety against anticipated-transient-without-scram (ATWS) events without alternative actions. Initiation of an automatic depressurization system provides effective heat removal from the fuel rods. An “in-vessel accumulator” effect of the reactor vessel top dome enhances the fuel rod cooling. This effect enlarges the safety margin for large LOCA.

Development of an information reference system using reconstruction models of nuclear power plants

Yuki Harazono,Taro Kimura,Hirotake Ishii,Hiroshi Shimoda,Yuya Kouda 한국원자력학회 2018 Nuclear Engineering and Technology Vol.50 No.4

Many nuclear power plants in Japan are approaching the end of their planned operational life spans. They must be decommissioned safely in the near future. Using augmented reality (AR), workers canintuitively understand information related to decommissioning work. Three-dimensional (work-site)reconstruction models of dismantling fields are useful for workers to observe the conditions ofdismantling field situations without visiting the actual fields. This study, based on AR and work-sitereconstruction models, developed and evaluated an information reference system. The evaluation consistsof questionnaires and interview surveys administered to six nuclear power plant workers who usedthis system, along with a scenario. Results highlight the possibility of reducing time and mitigatingmistakes in dismantling fields. Results also show the ease of referring to information in dismantlingfields. Nevertheless, it is apparently difficult for workers to build reconstruction models of dismantlingfields independently

Prognostic significance of tumor laterality in advanced ovarian cancer

( Yuki Yamada ),( Seiji Mabuchi ),( Naoki Kawahara ),( Ryuji Kawaguchi ) 대한산부인과학회 2021 Obstetrics & Gynecology Science Vol.64 No.6

Objective This study aimed to investigate the effect of incorporating tumor laterality into the International Federation of Gynecology and Obstetrics (FIGO) staging system for advanced ovarian cancer. Methods The clinical data of 131 patients with advanced ovarian cancer treated between 2008 and 2018 were retrospectively reviewed. To investigate the prognostic significance of tumor laterality, we divided the patients into unilateral and bilateral groups. The prognostic significance of tumor laterality (bilateral vs. unilateral) was evaluated using univariate and multivariate analyses. The effect of incorporating tumor laterality into the FIGO staging system to predict survival outcomes was evaluated using the Kaplan-Meier method. Results Both overall survival (OS) and progression-free survival (PFS) were longer in the unilateral group than in the bilateral group. Multivariate analysis demonstrated that tumor laterality was an independent predictor of OS (hazard ratio, 1.75; confidence interval, 1.05-2.92; P=0.032). In patients with stage III disease, the bilateral group had a shorter OS than the unilateral group, but it was comparable to the OS in stage IV patients (P=0.354). The incorporation of tumor laterality into the FIGO staging system improved the stratification of survival probabilities. Conclusion Tumor laterality can be an independent prognostic factor in patients with advanced ovarian cancer. The incorporation of tumor laterality may improve the predictive performance of the FIGO staging system in patients with advanced ovarian cancer.

Predictive Factors for Inaccurate Diagnosis of Swollen Lymph Nodes in Endoscopic Ultrasound-Guided Fine Needle Aspiration

Yuki Fujii,Yoshihide Kanno,Shinsuke Koshita,Takahisa Ogawa,Hiroaki Kusunose,Kaori Masu,Toshitaka Sakai,Keisuke Yonamine,Yujiro Kawakami,Toji Murabayashi,Fumisato Kozakai,Yutaka Noda,Hiroyuki Okada,Kei 대한소화기내시경학회 2019 Clinical Endoscopy Vol.52 No.2

Background/Aims: This study aimed to identify the predictive factors for inaccurate endoscopic ultrasound-guided fine needleaspiration (EUS-FNA) diagnosis of swollen lymph nodes without rapid on-site cytopathological evaluation. Methods: Eighty-three consecutive patients who underwent EUS-FNA for abdominal or mediastinal lymph nodes from January2008 to June 2017 were included from a prospectively maintained EUS-FNA database and retrospectively reviewed. The sensitivity,specificity, and accuracy of EUS-FNA for the detection of neoplastic diseases were calculated. Candidate factors for inaccurate diagnosis(lymph node size and location, needle type, puncture route, number of passes, and causative disease) were evaluated by comparisonbetween accurately diagnosed cases and others. Results: The final diagnosis of the punctured lymph node was classified as neoplastic (65 cases: a metastatic lymph node, malignantlymphoma, or Crow-Fukase syndrome) or non-neoplastic (18 cases: a reactive node or amyloidosis). The sensitivity, specificity, andaccuracy were 83%, 94%, and 86%, respectively. On multivariate analyses, small size of the lymph node was the sole predictive factor forinaccurate EUS-FNA diagnosis with a significant difference (odds ratios, 19.8; 95% confidence intervals, 3.15–124; p=0.0015). Conclusions: The lymph node size of <16 mm was the only independent factor associated with inaccurate EUS-FNA diagnosis ofswollen lymph nodes.

Examination on Fatigue Limit and Crack Growth Characteristic of SBHS700 Base Metal

Yuki Ono,Koji Kinoshita 한국강구조학회 2018 International Journal of Steel Structures Vol.18 No.4

The object of this study is to clarify fatigue limit and fatigue crack growth characteristic of SBHS700 base metal which is 780 MPa class steel. This study carried out the fatigue tests of SBHS700 base metal containing diff erent defect size, and the fatigue limit was compared with that of the conventional steel. Test results indicate that the fatigue limit increased with decrease initial defect size, and can be precisely evaluated by using √area parameter model. This paper also presents that crack growth characteristic was almost the same as that of the conventional steel from the observation of striations by using Scanning electron microscope and length of beach marks.