249 results on '"Hiroyuki Morimoto"'
Search Results
2. Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats
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Haruki Nishimura, Mitsuhiro Yoshimura, Makiko Shimizu, Kenya Sanada, Satomi Sonoda, Kazuaki Nishimura, Kazuhiko Baba, Naofumi Ikeda, Yasuhito Motojima, Takashi Maruyama, Yuki Nonaka, Ryoko Baba, Tatsushi Onaka, Takafumi Horishita, Hiroyuki Morimoto, Yasuhiro Yoshida, Makoto Kawasaki, Akinori Sakai, Masafumi Muratani, Becky Conway-Campbell, Stafford Lightman, and Yoichi Ueta
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Biology (General) ,QH301-705.5 - Abstract
The analgesic effect of oxytocin appears to be mediated via an oxytocin receptor and endogenous oxytocin contributes to the anti-nociception and anti-inflammatory response.
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- 2022
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3. The protein kinase R modifies gut physiology to limit colitis
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Howard Chi Ho Yim, Arindam Chakrabarti, Sean Kessler, Hiroyuki Morimoto, Die Wang, Dhanya Sooraj, Afsar U. Ahmed, Carol de la Motte, Robert H. Silverman, Bryan RG. Williams, and Anthony J. Sadler
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colitis ,protein kinase ,inflammasomes ,autophagy ,goblet cells ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Here we investigate the function of the innate immune molecule protein kinase R (PKR) in intestinal inflammation. To model a colitogenic role of PKR, we determine the physiological response to dextran sulfate sodium (DSS) of wild-type and two transgenic mice strains mutated to express either a kinase-dead PKR or to ablate expression of the kinase. These experiments recognize kinase-dependent and -independent protection from DSS-induced weight loss and inflammation, against a kinase-dependent increase in the susceptibility to DSS-induced injury. We propose these effects arise through PKR-dependent alteration of gut physiology, evidenced as altered goblet cell function and changes to the gut microbiota at homeostasis that suppresses inflammasome activity by controlling autophagy. These findings establish that PKR functions as both a protein kinase and a signaling molecule in instituting immune homeostasis in the gut.
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- 2023
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4. Effects of bicarbonate/lactate-buffered neutral peritoneal dialysis fluids on angiogenesis-related proteins in patients undergoing peritoneal dialysis
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Hiromichi Ueno, Tetsu Miyamoto, Hiroyuki Morimoto, Kenya Sanada, Ikutaro Furuno, Kazutoshi Nakazono, Emi Hasegawa, Akihiro Kuma, Yasushi Oginosawa, Yuki Tsuda, Masaru Araki, Masahito Tamura, Yoichi Ueta, Yutaka Otsuji, and Masaharu Kataoka
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Bicarbonate/lactate-buffered neutral peritoneal dialysis fluid ,Angiogenesis ,Growth-related oncogene ,Biocompatibility ,Chemokine ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background In order to facilitate the safe and long-term delivery of peritoneal dialysis (PD), it is necessary to improve the biocompatibility of peritoneal dialysis fluids (PDFs). The novel bicarbonate/lactate-buffered neutral PDFs (B/L-PDFs) are expected to be improved biocompatible. This study evaluated the biocompatibility of B/L-PDFs by analysis on the profile of angiogenesis-related proteins in drained dialysate of patients undergoing PD. Methods Concentrations of 20 angiogenesis-related proteins in the dialysate were semi-quantitatively determined using a RayBio® Human Angiogenesis Antibody Array and were compared between B/L-PDFs and conventional lactate-buffered neutral PDFs (L-PDFs). Results The expression of growth-related oncogene (GRO α/β/γ), which belongs to the CXC chemokine family, decreased significantly after use of the B/L-PDFs compared to the L-PDFs (P = 0.03). The number of the proteins with lower level in the B/L-PDFs compared with L-PDFs was significantly negatively correlated with the PD duration (Spearman ρ = − 0.81, P = 0.004). Conclusion This study suggested that B/L-PDFs are more biocompatible than conventional PDFs.
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- 2021
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5. A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia
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Tsukasa Shimauchi, Takuro Numaga-Tomita, Yuri Kato, Hiroyuki Morimoto, Kosuke Sakata, Ryosuke Matsukane, Akiyuki Nishimura, Kazuhiro Nishiyama, Atsushi Shibuta, Yutoku Horiuchi, Hitoshi Kurose, Sang Geon Kim, Yasuteru Urano, Takashi Ohshima, and Motohiro Nishida
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canonical transient receptor potential 6 ,peripheral arterial disease ,vessel maturation ,1-benzilpiperadine ,Cytology ,QH573-671 - Abstract
Retarded revascularization after progressive occlusion of large conductance arteries is a major cause of bad prognosis for peripheral artery disease (PAD). However, pharmacological treatment for PAD is still limited. We previously reported that suppression of transient receptor potential canonical (TRPC) 6 channel activity in vascular smooth muscle cells (VSMCs) facilitates VSMC differentiation without affecting proliferation and migration. In this study, we found that 1-benzilpiperadine derivative (1-BP), a selective inhibitor for TRPC3 and TRPC6 channel activities, induced VSMC differentiation. 1-BP-treated mice showed increased capillary arterialization and improvement of peripheral circulation and skeletal muscle mass after hind-limb ischemia (HLI) in mice. 1-BP had no additive effect on the facilitation of blood flow recovery after HLI in TRPC6-deficient mice, suggesting that suppression of TRPC6 underlies facilitation of the blood flow recovery by 1-BP. 1-BP also improved vascular nitric oxide bioavailability and blood flow recovery after HLI in hypercholesterolemic mice with endothelial dysfunction, suggesting the retrograde interaction from VSMCs to endothelium. These results suggest that 1-BP becomes a potential seed for PAD treatments that target vascular TRPC6 channels.
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- 2022
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6. Modulation of inflammatory responses by fractalkine signaling in microglia.
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Koichi Inoue, Hiroyuki Morimoto, Masahiro Ohgidani, and Takatoshi Ueki
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Medicine ,Science - Abstract
Reactive microglia are suggested to be involved in neurological disorders, and the mechanisms underlying microglial activity may provide insights into therapeutic strategies for neurological diseases. Microglia produce immunological responses to various stimuli, which include fractalkine (FKN or CX3CL1). CX3CR1, a FKN receptor, is present in microglial cells, and when FKN is applied before lipopolysaccharide (LPS) administration, LPS-induced inflammatory responses are inhibited, suggesting that the activation of the FKN signal is beneficial. Considering the practical administration for treatment, we investigated the influence of FKN on immunoreactive microglia using murine primary microglia and BV-2, a microglial cell line. The administration of LPS leads to nitric oxide (NO) production. NO was reduced when FKN was administered 4 h after LPS administration without a change in inducible nitric oxide synthase expression. In contrast, morphological changes, migratory activity, and proliferation were not altered by delayed FKN treatment. LPS decreases the CX3CR1 mRNA concentration, and the overexpression of CX3CR1 restores the FKN-mediated decrease in NO. CX3CR1 overexpression decreased the NO production that is mediated by LPS even without the application of FKN. ATP and ethanol also reduced CX3CR1 mRNA concentrations. In conclusion, the delayed FKN administration modified the LPS-induced microglial activation. The FKN signals were attenuated by a reduction in CX3CR1 by some inflammatory stimuli, and this modulated the inflammatory response of microglial cells, at least partially.
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- 2021
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7. Prophylactic steroid administration for strictures after endoscopic resection of large superficial esophageal squamous cell carcinoma
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Tomohiro Kadota, Tomonori Yano, Tomoji Kato, Maomi Imajoh, Masaaki Noguchi, Hiroyuki Morimoto, Shozo Osera, Yusuke Yoda, Yasuhiro Oono, Hiroaki Ikematsu, Atsushi Ohtsu, and Kazuhiro Kaneko
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and study aims: One of the major complications after endoscopic resection (ER) for large superficial esophageal squamous cell carcinoma (ESCC) is benign esophageal stricture, which can reduce quality of life even if ESCC achieves a cure without organ resection. Recently, steroid administration has been reported as a prophylactic treatment to prevent esophageal strictures. This retrospective study evaluated the stricture rate according to the different width of mucosal defects due to ER and compared it to that seen with prophylactic steroid administration. Patients and methods: Between June 2007 and December 2013, we enrolled patients with ESCC who had 3/4 or larger circumferential mucosal defects due to ER. In December 2009, steroid injections (triamcinolone acetonide 50 mg) into the ulcer bed due to ER were introduced. Beginning in November 2012, we commenced oral steroid administration (prednisolone 30 mg/day, tapered gradually for 8 weeks) in addition to steroid injection. Patients were classified into 3 groups according to the width of mucosal defect after ER (Group A, ≥ 3/4 and
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- 2016
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8. Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function
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Hirohiko Okamura, Kaya Yoshida, Hiroyuki Morimoto, Jumpei Teramachi, Kazuhiko Ochiai, Tatsuji Haneji, and Akihito Yamamoto
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protein phosphatase ,bone formation ,osteoblast differentiation ,osteosarcoma cells ,osteoclastogenesis ,adipogenesis ,Medicine - Abstract
The reversible phosphorylation of proteins plays hugely important roles in a variety of cellular processes, such as differentiation, proliferation, and apoptosis. These processes are strictly controlled by protein kinases (phosphorylation) and phosphatases (de-phosphorylation). Here we provide a brief history of the study of protein phosphorylation, including a summary of different types of protein kinases and phosphatases. One of the most physiologically important serine/threonine phosphatases is PP2A. This review provides a description of the phenotypes of various PP2A transgenic mice and further focuses on the known functions of PP2A in bone formation, including its role in osteoblast differentiation and function. A reduction in PP2A promotes bone formation and osteoblast differentiation through the regulation of bone-related transcription factors such as Osterix. Interestingly, downregulation of PP2A also stimulates adipocyte differentiation from undifferentiated mesenchymal cells under the appropriate adipogenic differentiation conditions. In osteoblasts, PP2A is also involved in the ability to control osteoclastogenesis as well as in the proliferation and metastasis of osteosarcoma cells. Thus, PP2A is considered to be a comprehensive factor in controlling the differentiation and function of cells derived from mesenchymal cells such as osteoblasts and adipocytes.
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- 2017
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9. Organocatalytic Direct Enantioselective Hydrophosphonylation of N-Unsubstituted Ketimines for the Synthesis of α-Aminophosphonates
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Koki Yamada, Yuta Kondo, Akihiko Kitamura, Tetsuya Kadota, Hiroyuki Morimoto, and Takashi Ohshima
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General Chemistry ,Catalysis - Published
- 2023
10. O- and N-Selective Electrophilic Activation of Allylic Alcohols and Amines in Pd-Catalyzed Direct Alkylation
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Lu Lin, Shunsuke Kataoka, Kiichi Hirayama, Ryozo Shibuya, Kenji Watanabe, Hiroyuki Morimoto, and Takashi Ohshima
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Drug Discovery ,General Chemistry ,General Medicine - Published
- 2023
11. The expression of matrix metalloproteinase-12 in the peritoneum of rats with continuous peritoneal dialysis
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Emi Hasegawa, Tetsu Miyamoto, Ryoko Baba, Keiji Kokubu, Kenta Nakamura, Masaharu Kataoka, and Hiroyuki Morimoto
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Nephrology ,Physiology ,Physiology (medical) - Abstract
Peritoneal dialysis (PD) is an important alternative treatment for end-stage renal disease. Continuous exposure to non-physiological fluids during PD is associated with pathological responses, such as sustained microinflammation, leading to tissue fibrosis and angiogenesis. However, the effect of PD fluid on submesothelial cells has not yet been investigated in detail.We investigated the association between macrophages and the expression of matrix metalloproteinase-12 (MMP-12), an elastin proteinase secreted by macrophages, in the peritoneal tissue of rats undergoing continuous PD.Morphological data revealed that the submesothelial layer of the peritoneum in PD model rats was markedly thickened, with fibrosis and angiogenesis. In the fibrillization area, elastin was disorganized and fragmented, and macrophages accumulated, which tended to have M2 characteristics. The expression of MMP-12 was enhanced by continuous exposure to PD fluid, suggesting that MMP-12 expression may be involved in PD fluid-induced peritoneal damage.The results of this study may lead to a better understanding of the mechanisms underlying fibrosis in PD.
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- 2022
12. One-Pot Catalytic Synthesis of α-Tetrasubstituted Amino Acid Derivatives via In Situ Generation of N-Unsubstituted Ketimines
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Yuta Kondo, Yoshinobu Hirazawa, Tetsuya Kadota, Koki Yamada, Kazuhiro Morisaki, Hiroyuki Morimoto, and Takashi Ohshima
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2022
13. Functional Group Evaluation Kit for Digitalization of Information on the Functional Group Compatibility and Chemoselectivity of Organic Reactions
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Natsuki Saito, Anna Nawachi, Yuta Kondo, Jeesoo Choi, Hiroyuki Morimoto, and Takashi Ohshima
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General Chemistry - Published
- 2023
14. Paneth cell maturation is related to epigenetic modification during neonatal–weaning transition
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Ryoko Baba, Keiji Kokubu, Kenta Nakamura, Mamoru Fujita, and Hiroyuki Morimoto
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Medical Laboratory Technology ,Histology ,Cell Biology ,digestive system ,Molecular Biology - Abstract
Paneth cells are antimicrobial peptide-secreting epithelial cells located at the bottom of the intestinal crypts of Lieberkühn. Crypts begin to form around day 7 of postnatal mice (P7), and Paneth cells usually appear within the first 2 weeks. Paneth cell dysfunction has been reported to correlate with Crohn’s disease-like inflammation, showing narrow crypts or loss of crypt architecture in mice. The morphology of dysfunctional Paneth cells is similar to that of a Paneth/goblet intermediate cell. However, it remains unclear whether the formation of the crypt is related to the maturation of Paneth cells. In this study, we investigated the histological changes in the mouse ileum postnatally and assessed the effect of the methyltransferase inhibitor on epithelium development using organoid culture. The morphological and functional maturation of Paneth cells occurred in the first 2 weeks and was accompanied by histone H3 lysine 27 (H3K27) trimethylation. Inhibition of H3K27 trimethylation suppressed crypt formation and Paneth cell maturation on organoids derived from ileum of early second postnatal mouse. Overall, our data show that post-transcriptional modification of histones, particularly H3K27 trimethylation, leads to the structural and functional maturation of Paneth cells during postnatal development.
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- 2022
15. Effects of a walking program in patients with chronic unilateral vestibular hypofunction
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Hayato, Asai, Satona, Murakami, Hiroyuki, Morimoto, Yuji, Asai, Eric G, Johnson, Yutaka, Yamashita, Mitsuya, Horiba, Yoko, Mizutani, Kayoko, Kabaya, and Yoshino, Ueki
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Physical Therapy, Sports Therapy and Rehabilitation - Abstract
[Purpose] Patients with chronic unilateral vestibular hypofunction show decreased postural stability and low levels of physical activity and also experience much anxiety. Physical activity is known to improve these symptoms; however, no study has reported any positive effects of physical activity, such as symptom reduction or improvement in function in these patients. In this study, we investigated the role of a walking program in improvement of dizziness, anxiety, and postural stability in this patient population. [Participants and Methods] This study included 21 patients with unilateral vestibular hypofunction and chronic dizziness. Patients were instructed to walk 30 min daily for 3 months. Physical activity levels and questionnaires for clinical symptoms, anxiety, and postural stability were evaluated before and after intervention. [Results] We observed significant differences in the amount of moderate-to-vigorous physical activity, clinical symptoms, and self-perceived handicap before and after the intervention. Additionally, anxiety levels were significantly reduced and postural stability was significantly improved in these patients. [Conclusion] A walking program improved physical activity levels, clinical symptoms, and postural stability and reduced self-perceived handicap and anxiety in patients with chronic unilateral vestibular hypofunction. These results highlight the effectiveness of a walking program for these patients and emphasize its role as a complementary vestibular rehabilitation strategy.
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- 2022
16. Development of Greener Catalytic Synthetic Methods of Nitrogen-Containing Compounds Using N-Unprotected Ketimines
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Hiroyuki Morimoto
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Organic Chemistry - Published
- 2022
17. Direct Catalytic Enantioselective Hydrophosphonylation of N-Unsubstituted Ketimines
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Koki Yamada, Yuta Kondo, Akihiko Kitamura, Tetsuya Kadota, Hiroyuki Morimoto, and Takashi Ohshima
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We report a direct catalytic enantioselective hydrophosphonylation of N-unsubstituted ketimines that affords N-unprotected α-tetrasubstituted α-aminophosphonates without protection/deprotection steps. The reaction is suitable for N-unsubstituted isatin-derived ketimines and N-unsubstituted trifluoromethyl ketimines, affording products in high yields with excellent enantioselectivity. Applications of the reaction and a proposed transition state model are also described.
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- 2022
18. Effect of Amino Acid Addition on the Crystallization of Asparagine
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Hideki Nabika, Kei Unoura, and Hiroyuki Morimoto
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chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Stereochemistry ,fungi ,food and beverages ,General Chemistry ,010402 general chemistry ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,law.invention ,Amino acid ,law ,General Materials Science ,Asparagine ,Crystallization - Abstract
Understanding how the crystallization of one amino acid is affected by other coexisting amino acids is important for the industrial crystallization of chiral molecules and can also help reveal the ...
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- 2021
19. A simple preparation method for CLEM using pre-embedding immunohistochemistry with a novel fluorescent probe and stable embedding resin
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Kei-ichiro Nakamura, Kentaro Nishi, Hiroyuki Morimoto, Teruyoshi Kondo, Shin-ichiro Isobe, and Takaaki Kanemaru
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0106 biological sciences ,Materials science ,Magnification ,01 natural sciences ,Specimen Handling ,03 medical and health sciences ,chemistry.chemical_compound ,Immunolabeling ,Optics ,Structural Biology ,Radiology, Nuclear Medicine and imaging ,Instrumentation ,Cellular localization ,Fluorescent Dyes ,030304 developmental biology ,0303 health sciences ,business.industry ,Osmium ,Immunohistochemistry ,Fluorescence ,Microscopy, Electron ,Osmium tetroxide ,chemistry ,Transmission electron microscopy ,Cathode ray ,Durcupan ,business ,010606 plant biology & botany - Abstract
Correlative light and electron microscopy (CLEM) is an excellent approach for examining the cellular localization of biomolecules. Here, we developed a simple method for CLEM by combining pre-embedding immunohistochemistry with a novel fluorescent probe, namely Fluolid NS Orange, and an embedding resin called ʻDurcupan™ʼ. Specimens were embedded in Durcupan™ or LR White after immunolabeling and post-fixation using glutaraldehyde and osmium tetroxide. Next, ultrathin sections were prepared on a finder grid with navigation markers. The section of the specimen embedded in Durcupan™ was found to be more stable against electron beam irradiation than specimens embedded in LR White. A fluorescence light microscopy image and a transmission electron microscopy (TEM) image, at wide-field, and low magnification, were independently obtained with the same ultrathin section. Using the three corners between finder grid bars as landmarks, fluorescence light microscopy images were superimposed with wide-field, low-magnification TEM images to identify the region of interest, which was subsequently enlarged to ascertain cellular structures localized beneath fluorescent signals. However, the enlarged TEM images appeared blurred, and fluorescence signals had a hazy appearance. To resolve this, the enlarged TEM images were replaced by high-resolution TEM images focused directly on the region of interest, thereby facilitating the collection of high-resolution CLEM images. The simple sample processing method for CLEM using osmium-resistant Fluolid NS Orange and electron beam damage-resistant Durcupan™ allowed the determination of the precise localization of fluorescence signals at subcellular levels.
- Published
- 2021
20. An Electrically Adjustable 3-Terminal Regulator for Post-Fabrication Level-Trimming with a Reliable 1-Wire Serial I/O.
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Hiroyuki Morimoto, Hiroki Koike, and Kazuyuki Nakamura
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- 2011
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21. The protein kinase R modifies gut physiology to limit colitis.
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Chi Ho Yim, Howard, Chakrabarti, Arindam, Kessler, Sean, Hiroyuki Morimoto, Die Wang, Sooraj, Dhanya, Ahmed, Afsar U., de la Motte, Carol, Silverman, Robert H., Williams, Bryan R. G., and Sadler, Anthony J.
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COLITIS ,PHYSIOLOGY ,CELL physiology ,DEXTRAN sulfate ,TRANSGENIC mice ,PROTEIN kinases - Abstract
Here we investigate the function of the innate immune molecule protein kinase R (PKR) in intestinal inflammation. To model a colitogenic role of PKR, we determine the physiological response to dextran sulfate sodium (DSS) of wild-type and two transgenic mice strains mutated to express either a kinase-dead PKR or to ablate expression of the kinase. These experiments recognize kinase-dependent and -independent protection from DSS-induced weight loss and inflammation, against a kinase-dependent increase in the susceptibility to DSS-induced injury. We propose these effects arise through PKR-dependent alteration of gut physiology, evidenced as altered goblet cell function and changes to the gut microbiota at homeostasis that suppresses inflammasome activity by controlling autophagy. These findings establish that PKR functions as both a protein kinase and a signaling molecule in instituting immune homeostasis in the gut. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Recent Progress on Catalytic Addition Reactions to N-Unsubstituted Imines
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Kazuhiro Morisaki, Hiroyuki Morimoto, and Takashi Ohshima
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Green chemistry ,Addition reaction ,010405 organic chemistry ,Chemistry ,fungi ,food and beverages ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,One pot reaction ,Direct process - Abstract
Catalytic addition reactions to N-unsubstituted (N-unprotected) imines can provide a more straightforward synthesis of amines. This direct process eliminates the unnecessary protecting-group manipu...
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- 2020
23. Recent Progress towards the Use of Benzophenone Imines as an Ammonia Equivalent
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Yuta Kondo, Takashi Ohshima, and Hiroyuki Morimoto
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chemistry.chemical_compound ,Ammonia ,Primary (chemistry) ,010405 organic chemistry ,Chemistry ,Imine ,Benzophenone ,Organic chemistry ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Amination ,0104 chemical sciences - Abstract
Benzophenone imine and its derivatives are useful ammonia equivalents for synthesizing primary amines, readily achieving the selective formation of primary amines and obtaining easily deprotectable...
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- 2020
24. Scandium(III) Triflate Catalyzed Direct Synthesis of N-Unprotected Ketimines
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Yuta Kondo, Kazuhiro Morisaki, Tetsuya Kadota, Takashi Ohshima, Yoshinobu Hirazawa, and Hiroyuki Morimoto
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Reaction mechanism ,Schiff base ,010405 organic chemistry ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Reagent ,Functional group ,Lewis acids and bases ,Scandium ,Physical and Theoretical Chemistry ,Trifluoromethanesulfonate - Abstract
N-Unprotected ketimines are useful substrates and intermediates for synthesizing valuable nitrogen-containing compounds, but their potential applicability is limited by the available synthetic methods. To address this issue, we report a scandium(III) triflate catalyzed direct synthesis of N-unprotected ketimines. Using commercially available reagents and Lewis acid catalysts, ketones were directly transformed into the corresponding N-unprotected ketimines in high yields with broad functional group tolerance, even in multigram scales. The reactions were readily applicable for one-pot synthesis of important compounds such as a glycine Schiff base without isolation of N-unprotected ketimine intermediates. Preliminary mechanistic studies to clarify the reaction mechanism are also described.
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- 2019
25. Particulate Matter, Asian Sand Dust Delays Cyclophosphamide-induced Type 1 Diabetes in NOD Mice
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Yuan Song, Duo Wang, Ryoko Baba, Tamotsu Kanazawa, Kentaro Morita, Hiroyuki Morimoto, and Yasuhiro Yoshida
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Cyclophosphamide ,Immunology ,Spleen ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Immunomodulation ,Mice ,Mice, Inbred NOD ,Sand ,Diabetes mellitus ,medicine ,Splenocyte ,Animals ,Lymphocytes ,NOD mice ,Autoimmune disease ,Type 1 diabetes ,business.industry ,Incidence (epidemiology) ,Dust ,General Medicine ,medicine.disease ,Disease Models, Animal ,Diabetes Mellitus, Type 1 ,medicine.anatomical_structure ,Cytokines ,Female ,Particulate Matter ,Disease Susceptibility ,business ,medicine.drug - Abstract
Although it is known that desert dust exacerbates allergic diseases, how it affects the onset of autoimmune diseases is unclear. No epidemiological investigations or animal experiments have been conducted so far to elucidate the effects of desert dust on autoimmune diseases. Here, we focused on particulate matter, such Asian sand dust (ASD) that has been known to cause adverse health effects in East Asian countries, and conducted animal experiments to examine how ASD influences type 1 diabetes (T1D), an autoimmune disease. An ASD suspension was intratracheally administered into NOD mice, which spontaneously develop T1D, for 4 times at 2-week intervals. Subsequently, the incidence of cyclophosphamide (CY)-induced diabetes was examined, which was then quantified using adoptive splenocyte-transfer assays. Kaplan-Meier curves of the cumulative T1D incidence were compared using the log-rank test, and unpaired two-tailed t tests were used for comparing the other data. We observed that ASD administration delayed T1D, and adoptive splenocytes derived from ASD-administered donor NOD mice also delayed the onset of T1D in recipient NOD mice. We further found that ASD increases concanavalin A-induced IFN-γ production and decreases regulatory T cells. Consequently, ASD suppresses the onset of T1D, activates spleen cells, and affects T-cell differentiation.
- Published
- 2019
26. Calmodulin and protein kinases A/G mediate ciliary beat response in the human nasal epithelium
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Thi Nga Nguyen, Toyoaki Ohbuchi, Takuro Kitamura, Ryoko Baba, Hiroyuki Morimoto, Hideaki Suzuki, Tetsuro Wakasugi, Jun-ichi Ohkubo, and Ba Hung Do
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Adult ,Male ,Adolescent ,Calmodulin ,Immunoelectron microscopy ,Nerve Tissue Proteins ,Connexins ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cyclic GMP-Dependent Protein Kinases ,Humans ,Immunology and Allergy ,Medicine ,Calcium Signaling ,Cilia ,030223 otorhinolaryngology ,Protein kinase A ,Cells, Cultured ,Aged ,Aged, 80 and over ,biology ,Kinase ,business.industry ,Middle Aged ,KT5720 ,Cyclic AMP-Dependent Protein Kinases ,Rhinitis, Allergic ,Protein Kinase A Inhibitor ,Cell biology ,Nasal Mucosa ,030228 respiratory system ,Otorhinolaryngology ,chemistry ,Mucociliary Clearance ,biology.protein ,Respiratory epithelium ,Female ,Receptors, Purinergic P2X7 ,business ,cGMP-dependent protein kinase - Abstract
Background Mucociliary clearance of the airway epithelium is an essential function for mucosal defense. We recently proposed a hypothetical mechanism of ciliary beat regulation, in which the pannexin-1 (Panx1)-P2X7 unit serves as an oscillator generating a periodic increase in intracellular Ca2+ ([Ca2+ ]i ). In the present study, we examined the localization of Panx1 and P2X7 at the ultrastructural level, and investigated the regulatory pathway subsequent to [Ca2+ ]i increase. Methods The inferior turbinate mucosa was collected from patients with chronic hypertrophic rhinitis during endoscopic sinonasal surgery. The mucosa was examined by transmission immunoelectron microscopy for Panx1 and P2X7. Alternatively, the mucosa was cut into thin strips, and ciliary beat frequency (CBF) was measured under a phase-contrast light microscope with a high-speed digital video camera. Results In immunoelectron microscopy, immunoreactivities for Panx1 and P2X7 were localized along the plasma membrane of the entire length of the cilia. CBF was significantly increased by stimulation with 100 µM acetylcholine (Ach). The Ach-induced CBF increase was significantly inhibited by calmidazolium (calmodulin antagonist), SQ22536 (adenylate cyclase inhibitor), ODQ (guanylate cyclase inhibitor), KT5720 (protein kinase A inhibitor), and KT5823 (protein kinase G inhibitor). Fluorodinitrobenzene (creatine kinase inhibitor) completely inhibited the ciliary beat in a time- and dose-dependent manner. Conclusion These results indicate that Panx1 and P2X7 coexist at the cilia of the human nasal epithelial cells and that the ciliary beat is regulated by calmodulin, adenylate/guanylate cyclases and protein kinases A/G, and crucially depends on creatine kinase.
- Published
- 2019
27. Pentacyclic triterpenoid ursolic acid induces apoptosis with mitochondrial dysfunction in adult T-cell leukemia MT-4 cells to promote surrounding cell growth
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Mengyue Shen, Duo Wang, Yusuke Sennari, Zirui Zeng, Ryoko Baba, Hiroyuki Morimoto, Noriaki Kitamura, Tsukasa Nakanishi, Junichi Tsukada, Masanobu Ueno, Yasuyuki Todoroki, Shigeru Iwata, Tomo Yonezawa, Yoshiya Tanaka, Yoshio Osada, and Yasuhiro Yoshida
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Cancer Research ,Caspase 3 ,Apoptosis ,Hematology ,General Medicine ,Poly(ADP-ribose) Polymerase Inhibitors ,Antineoplastic Agents, Phytogenic ,Triterpenes ,Mitochondria ,Oncology ,Cell Line, Tumor ,Leukocytes, Mononuclear ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Oleanolic Acid ,Cell Proliferation - Abstract
We investigated the antitumor effects of oleanolic acid (OA) and ursolic acid (UA) on adult T-cell leukemia cells. OA and UA dose-dependently inhibited the proliferation of adult T-cell leukemia cells. UA-treated cells showed caspase 3/7 and caspase 9 activation. PARP cleavage was detected in UA-treated MT-4 cells. Activation of mTOR and PDK-1 was inhibited by UA. Autophagosomes were detected in MT-4 cells after UA treatment using electron microscopy. Consistently, mitophagy was observed in OA- and UA-treated MT-4 cells by confocal microscopy. The mitochondrial membrane potential in MT-4 cells considerably decreased, and mitochondrial respiration and aerobic glycolysis were significantly reduced following UA treatment. Furthermore, MT-1 and MT-4 cells were sorted into two regions based on their mitochondrial membrane potential. UA-treated MT-4 cells from both regions showed high activation of caspase 3/7, which were inhibited by Z-vad. Interestingly, MT-4 cells cocultured with sorted UA-treated cells showed enhanced proliferation. Finally, UA induced cell death and ex vivo PARP cleavage in peripheral blood mononuclear cells from patients with adult T-cell leukemia. Therefore, UA-treated MT-4 cells show caspase activation following mitochondrial dysfunction and may produce survival signals to the surrounding cells.
- Published
- 2021
28. Effects of bicarbonate/lactate-buffered neutral peritoneal dialysis fluids on angiogenesis-related proteins in patients undergoing peritoneal dialysis
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Ikutaro Furuno, Yutaka Otsuji, Masaru Araki, Yasushi Oginosawa, Kazutoshi Nakazono, Akihiro Kuma, Yuki Tsuda, Masahito Tamura, Hiromichi Ueno, Masaharu Kataoka, Hiroyuki Morimoto, Emi Hasegawa, Kenya Sanada, Yoichi Ueta, and Tetsu Miyamoto
- Subjects
Nephrology ,medicine.medical_specialty ,Biocompatibility ,Angiogenesis ,Urology ,medicine.medical_treatment ,Bicarbonate ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Pharmacology ,Peritoneal dialysis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,In patient ,Transplantation ,Oncogene ,business.industry ,Growth-related oncogene ,Biocompatible material ,Diseases of the genitourinary system. Urology ,Bicarbonate/lactate-buffered neutral peritoneal dialysis fluid ,chemistry ,Chemokine ,RC870-923 ,business - Abstract
Background In order to facilitate the safe and long-term delivery of peritoneal dialysis (PD), it is necessary to improve the biocompatibility of peritoneal dialysis fluids (PDFs). The novel bicarbonate/lactate-buffered neutral PDFs (B/L-PDFs) are expected to be improved biocompatible. This study evaluated the biocompatibility of B/L-PDFs by analysis on the profile of angiogenesis-related proteins in drained dialysate of patients undergoing PD. Methods Concentrations of 20 angiogenesis-related proteins in the dialysate were semi-quantitatively determined using a RayBio® Human Angiogenesis Antibody Array and were compared between B/L-PDFs and conventional lactate-buffered neutral PDFs (L-PDFs). Results The expression of growth-related oncogene (GRO α/β/γ), which belongs to the CXC chemokine family, decreased significantly after use of the B/L-PDFs compared to the L-PDFs (P = 0.03). The number of the proteins with lower level in the B/L-PDFs compared with L-PDFs was significantly negatively correlated with the PD duration (Spearman ρ = − 0.81, P = 0.004). Conclusion This study suggested that B/L-PDFs are more biocompatible than conventional PDFs.
- Published
- 2021
29. Catalytic Enantioselective Strecker Reaction of Isatin-Derived N-Unsubstituted Ketimines
- Author
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Takashi Ohshima, Tetsuya Kadota, Yuta Kondo, Hiroyuki Morimoto, and Masanao Sawa
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Isatin ,Organic Chemistry ,Strecker amino acid synthesis ,Enantioselective synthesis ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Amino acid ,Stereocenter ,Catalysis ,chemistry.chemical_compound ,Organic chemistry ,Stereoselectivity ,Physical and Theoretical Chemistry ,Carbon - Abstract
A catalytic enantioselective Strecker reaction of isatin-derived N-unsubstituted ketimines directly afforded the N-unprotected α-aminonitriles with a tetrasubstituted carbon stereocenter in up to 99% ee without requiring protection/deprotection steps. One-pot Strecker reactions from the parent carbonyl compounds were also realized with comparable yields and enantioselectivities. Direct transformations of the N-unprotected α-aminonitrile products streamlined the synthesis of unnatural amino acid derivatives and achieved the shortest one-pot stereoselective routes to a biologically active compound reported to date.
- Published
- 2021
30. Ammonium Salt-Accelerated Hydrazinolysis of Unactivated Amides: Mechanistic Investigation and Application to a Microwave Flow Process
- Author
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Yoshitaka Hamashima, Noriyuki Ohneda, Yuhei Shimizu, Takashi Ohshima, Hiromichi Odajima, Hiroyuki Morimoto, Shuji Akai, and Megumi Noshita
- Subjects
chemistry.chemical_classification ,Reaction mechanism ,010405 organic chemistry ,Organic Chemistry ,Hydrazine ,Salt (chemistry) ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Amide ,Organic chemistry ,Ammonium ,Amine gas treating ,Physical and Theoretical Chemistry ,Microwave - Abstract
A study of ammonium salt-accelerated hydrazinolysis of unactivated amides is described. We first studied the reaction mechanism by kinetic experiments and DFT calculations and found that cooperation of the hydrazinium salt and hydrazine is important for promoting the cleavage of unactivated amides. Next, we applied the reaction to a microwave flow process, and the amine products were isolated on a multigram scale.
- Published
- 2019
31. Low Cost High Efficiency Machining Technology for Aluminum Cutting—Development of Sensing of Cutting Force and Adaptive Control Machining
- Author
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Masahiko Masuda, Hayashi Kazuya, Hiroyuki Morimoto, Hideyuki Fujiwara, and Tomoaki Enomoto
- Subjects
Adaptive control ,chemistry ,Machining ,Computer science ,Aluminium ,Mechanical Engineering ,Cutting force ,Mechanical engineering ,chemistry.chemical_element - Published
- 2019
32. Differences in postural stability and dynamic visual acuity among healthy young adults in relation to sports activity: a cross sectional study
- Author
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Jun Mizutani, Everett Lohman, Ikuo Wada, Hayato Asai, Hiroyuki Morimoto, Eric G. Johnson, Yoshinori Koide, Eisuke Sakuma, Yuji Asai, Takatoshi Ueki, and Yoshino Ueki
- Subjects
Vestibular system ,030506 rehabilitation ,medicine.medical_specialty ,Dynamic visual acuity ,Visual acuity ,Cross-sectional study ,business.industry ,Postural stability ,Physical Therapy, Sports Therapy and Rehabilitation ,030229 sport sciences ,Head rotation ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,Original Article ,Sports activity ,medicine.symptom ,Young adult ,0305 other medical science ,business ,human activities ,Neck rotation ,Quiet standing - Abstract
[Purpose] Sports activity has been shown to improve postural stability and vestibular function in healthy older adults. The hypothesis was that healthy young adults undertaking sports activity will also have better postural stability and vestibular function compared with healthy young adults who do not undertake sports activity. The purpose of this study was to investigate the differences in postural stability and vestibular function between healthy young adults who undertake sports activity and those who do not undertake such activity. [Participants and Methods] Thirty-nine healthy young adults were recruited and divided into sports and non-sports groups on the basis of their response to a questionnaire concerning regular participation in sports activities over the past 12 months. In both groups, postural stability was measured during quiet standing and standing during head rotation, and dynamic visual acuity was assessed during head rotation. [Results] The results showed significant differences in postural stability during head rotation and dynamic visual acuity between the two groups, whereas no significant differences were found in postural stability during quiet standing. [Conclusion] The results suggest that healthy young adults who undertake sports activity have better postural stability during head rotation and better dynamic visual acuity. The causal effect of these differences is not clear and further investigation is warranted.
- Published
- 2019
33. Modulation of inflammatory responses by fractalkine signaling in microglia
- Author
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Masahiro Ohgidani, Koichi Inoue, Takatoshi Ueki, and Hiroyuki Morimoto
- Subjects
Lipopolysaccharides ,Lipopolysaccharide ,Gene Expression ,Pharmacology ,Biochemistry ,Neurological Signaling ,chemistry.chemical_compound ,Medical Conditions ,Cell Signaling ,Cell Movement ,Animal Cells ,CX3CR1 ,Medicine and Health Sciences ,Receptor ,Immune Response ,Cells, Cultured ,Multidisciplinary ,Microglia ,biology ,Neurochemistry ,Nitric oxide synthase ,medicine.anatomical_structure ,Medicine ,Hyperexpression Techniques ,medicine.symptom ,Cellular Types ,Neurochemicals ,Signal Transduction ,Research Article ,Science ,Inflammatory Diseases ,Immunoblotting ,Immunology ,CX3C Chemokine Receptor 1 ,Inflammation ,Enzyme-Linked Immunosorbent Assay ,Glial Cells ,Nitric Oxide ,Transfection ,Research and Analysis Methods ,Nitric oxide ,Signs and Symptoms ,medicine ,Genetics ,Gene Expression and Vector Techniques ,Humans ,RNA, Messenger ,CX3CL1 ,Molecular Biology Techniques ,Microglial Cells ,Molecular Biology ,Cell Proliferation ,Molecular Biology Assays and Analysis Techniques ,Chemokine CX3CL1 ,Biology and Life Sciences ,Cell Biology ,Macrophage Activation ,chemistry ,biology.protein ,Clinical Medicine ,Neuroscience - Abstract
Reactive microglia are suggested to be involved in neurological disorders, and the mechanisms underlying microglial activity may provide insights into therapeutic strategies for neurological diseases. Microglia produce immunological responses to various stimuli, which include fractalkine (FKN or CX3CL1). CX3CR1, a FKN receptor, is present in microglial cells, and when FKN is applied before lipopolysaccharide (LPS) administration, LPS-induced inflammatory responses are inhibited, suggesting that the activation of the FKN signal is beneficial. Considering the practical administration for treatment, we investigated the influence of FKN on immunoreactive microglia using murine primary microglia and BV-2, a microglial cell line. The administration of LPS leads to nitric oxide (NO) production. NO was reduced when FKN was administered 4 h after LPS administration without a change in inducible nitric oxide synthase expression. In contrast, morphological changes, migratory activity, and proliferation were not altered by delayed FKN treatment. LPS decreases the CX3CR1 mRNA concentration, and the overexpression of CX3CR1 restores the FKN-mediated decrease in NO. CX3CR1 overexpression decreased the NO production that is mediated by LPS even without the application of FKN. ATP and ethanol also reduced CX3CR1 mRNA concentrations. In conclusion, the delayed FKN administration modified the LPS-induced microglial activation. The FKN signals were attenuated by a reduction in CX3CR1 by some inflammatory stimuli, and this modulated the inflammatory response of microglial cells, at least partially.
- Published
- 2021
34. Development and Integration of New Green Reactions
- Author
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Tetsuya Kadota, Takashi Ohshima, and Hiroyuki Morimoto
- Subjects
Flow system ,Process (engineering) ,business.industry ,Computer science ,Atom economy ,One-pot synthesis ,Process engineering ,business ,Catalysis - Abstract
Over the last few decades, the quest for environmentally benign chemical transformations has become an important topic in both industrial and academic research. An integrated synthesis that combines multiple reactions in a single operation in a one-pot or a flow system without isolating intermediates has recently drawn much attention as a replacement for conventional step-by-step synthesis. Because in the reaction integration process the reaction mixtures are directly used to the next reaction without purification and the generated co- and by-products may have negative effects on the next reaction, integrating highly atom-economical reactions is quite important. To this end, we developed several highly atom-economical direct catalytic reactions. In this review, we focused on the developments of synthesis and reactions of N-unprotected ketimines and their applications for time integration (one-pot sequential process through N-unprotected ketimine synthesis).
- Published
- 2021
35. An electrically adjustable 3-terminal regulator with post-fabrication level-trimming function.
- Author
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Hiroyuki Morimoto, Hiroki Koike, and Kazuyuki Nakamura
- Published
- 2010
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36. C-C Bond Cleavage of Unactivated 2-Acylimidazoles
- Author
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Bo Pang, Jeesoo Choi, Hai Long Xin, Hiroyuki Morimoto, Walaa Akkad, and Takashi Ohshima
- Subjects
chemistry.chemical_classification ,chemistry ,010405 organic chemistry ,Carboxylic acid ,Reagent ,Organic Chemistry ,Enantioselective synthesis ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Bond cleavage ,0104 chemical sciences ,Catalysis - Abstract
2-Acylimidazoles are widely used as post-transformable carboxylic acid equivalents in chemoselective and enantioselective reactions. Their transformations, however, require pretreatment with highly reactive, toxic methylating reagents to facilitate C-C bond cleavage. Here, we demonstrate that such pretreatment can be avoided and the C-C bond cleaved under neutral conditions without the use of additional reagents or catalysts. The scope of the reaction, including the use of products reported in the literature as substrates, and some mechanistic insights are described.
- Published
- 2020
37. 3‐Mono‐Substituted BINOL Phosphoric Acids as Effective Organocatalysts in Direct Enantioselective Friedel–Crafts‐Type Alkylation of N‐Unprotected α‐Ketiminoester
- Author
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Walaa Akkad, Hiroyuki Morimoto, Kazuhiro Morisaki, Masanao Sawa, Yuta Kondo, Ryohei Yonesaki, and Takashi Ohshima
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Enantioselective synthesis ,General Chemistry ,Alkylation ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Amino acid ,Organic chemistry ,Brønsted–Lowry acid–base theory ,Friedel–Crafts reaction - Abstract
Although BINOL-derived phosphoric acids are among the most widely used chiral Brønsted acid organocatalysts, their structures are mostly limited to 3,3'-disubstituted ones and simple 3-mono-substituted ones without any polar functionalities on the 3-substituent have not been used in highly enantioselective reactions. This work reports such 3-mono-substituted analogues as effective organocatalysts in direct highly enantioselective Friedel-Crafts-type alkylation of N-unprotected α-ketiminoester. The origin of the observed high enantioselectivity with the 3-mono-substituted catalyst is also discussed.
- Published
- 2018
38. Rhodium(I)/Chiral Diene-Catalyzed Enantioselective Addition of Boronic Acids to N-Unsubstituted Isatin-Derived Ketimines
- Author
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Takashi Ohshima, Ibuki Kusagawa, Tamio Hayashi, Ryohei Yonesaki, and Hiroyuki Morimoto
- Subjects
Diene ,010405 organic chemistry ,Isatin ,Organic Chemistry ,Enantioselective synthesis ,chemistry.chemical_element ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Rhodium ,Adduct ,Catalysis ,chemistry.chemical_compound ,chemistry ,Yield (chemistry) ,Organic chemistry ,Boronic acid - Abstract
Enantioselective addition of boronic acids to N-unsubstituted isatin-derived ketimines was realized using rhodium(I)/chiral diene catalysts. The reactions can be performed in the presence of catalytic amounts of a base to give adducts in high yield with high enantioselectivity. Preliminary mechanistic information including a computational model to explain the observed enantioselectivity is also provided.
- Published
- 2019
39. Catalytic Enantioselective Decarboxylative Mannich-Type Reaction of N-Unprotected Isatin-Derived Ketimines
- Author
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Ryohei Yonesaki, Hiroyuki Morimoto, Shotaro Miyazaki, Takashi Ohshima, and Masanao Sawa
- Subjects
010405 organic chemistry ,Isatin ,Organic Chemistry ,Enantioselective synthesis ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Yield (chemistry) ,Organic chemistry ,Physical and Theoretical Chemistry - Abstract
The first catalytic enantioselective decarboxylative Mannich-type reaction of N-unprotected ketimines is reported, directly providing N-unprotected 3-tetrasubstituted 3-aminooxindoles in high yield and ee without protection/deprotection steps. The utility of this reaction is demonstrated in the short step synthesis of (+)-AG-041R.
- Published
- 2018
40. Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10
- Author
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Taishi Higashi, Keiichi Motoyama, Takashi Ohshima, Nozomi Sugimoto, Masatoshi Fujita, Hidetaka Kosako, Hidetoshi Arima, Masaki Yukuhiro, Takuya Yokoyama, Kazumasa Yoshida, Hiroyuki Morimoto, Chika Tanaka, Atsushi Shibuta, Kazunari Sankoda, Risa Fujiwara, and Yuka Iwasaki
- Subjects
Cell Survival ,Mice, Nude ,lcsh:Medicine ,Antineoplastic Agents ,Importin ,Biochemistry ,Article ,Polyethylene Glycols ,HeLa ,Mice ,chemistry.chemical_compound ,Affinity chromatography ,In vivo ,Animals ,Humans ,Moiety ,lcsh:Science ,Cancer ,Cell Proliferation ,Multidisciplinary ,biology ,Drug discovery ,Carbazole ,lcsh:R ,HCT116 Cells ,beta Karyopherins ,biology.organism_classification ,Chemical biology ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Nuclear Pore Complex Proteins ,Oncology ,chemistry ,Colonic Neoplasms ,lcsh:Q ,Antimitotic Agent ,Lead compound ,HeLa Cells - Abstract
We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents.
- Published
- 2019
41. Development of Direct Enantioselective Alkynylation of α-Ketoester and α-Ketiminoesters Catalyzed by Phenylbis(oxazoline)Rh(III) Complexes
- Author
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Hiroyuki Morimoto, Kazushi Mashima, Kazuhiro Morisaki, and Takashi Ohshima
- Subjects
Alkynylation ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Organic chemistry ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences - Published
- 2018
42. Boronic Acid Accelerated Three-Component Reaction for the Synthesis of α-Sulfanyl-Substituted Indole-3-acetic Acids
- Author
-
Kenji Watanabe, Amrita Das, Takashi Ohshima, and Hiroyuki Morimoto
- Subjects
inorganic chemicals ,Indole test ,chemistry.chemical_classification ,010405 organic chemistry ,Carboxylic acid ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Suzuki reaction ,chemistry ,Sulfanyl ,Intramolecular force ,Organic chemistry ,Product formation ,Physical and Theoretical Chemistry ,Boronic acid - Abstract
Boronic acid was used to accelerate a three-component reaction of indoles, thiols, and glyoxylic acids for the synthesis of α-sulfanyl-substituted indole-3-acetic acids. Boronic acid catalysis to activate the α-hydroxy group in α-hydroxycarboxylic acid intermediates and intramolecular assistance by free carboxylic acid were the keys to accelerating the product formation.
- Published
- 2017
43. Direct Catalytic Alcoholysis of Unactivated 8-Aminoquinoline Amides
- Author
-
Takashi Ohshima, Hiroyuki Morimoto, Hai Long Xin, and Toru Deguchi
- Subjects
8-Aminoquinoline ,010405 organic chemistry ,Regioselectivity ,Homogeneous catalysis ,General Chemistry ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Functional group ,Surface modification ,Organic chemistry ,Chemoselectivity - Abstract
Direct catalytic alcoholysis of unactivated amides is one of the most difficult challenges in organic chemistry, and an applicable method for cleaving amides used as directing groups in regioselective functionalization reactions has not been reported. Herein, we report direct catalytic alcoholysis of 8-aminoquinoline amides, which are highly effective directing groups in regioselective functionalization reactions. The reactions proceeded with a simple combination of substrates, air-stable catalysts, and alcohols, affording the corresponding esters in good yields with broad functional group tolerance. Highly chemoselective cleavage of the 8-aminoquinoline amides in the presence of related carbonyl functionalities and preliminary mechanistic studies are also described.
- Published
- 2017
44. Clinical impact of surveillance for head and neck cancer in patients with esophageal squamous cell carcinoma
- Author
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Ryuichi Hayashi, Hiroaki Ikematsu, Hiroyuki Morimoto, Yusuke Yoda, Kazuhiro Kaneko, Atsushi Ohtsu, Yasuhiro Oono, and Tomonori Yano
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Endoscopic Mucosal Resection ,Esophageal Neoplasms ,head and neck squamous cell carcinoma ,Esophageal squamous cell carcinoma ,Neoplasms, Multiple Primary ,03 medical and health sciences ,Narrow Band Imaging ,0302 clinical medicine ,endoscopic resection ,Retrospective Study ,Internal medicine ,medicine ,Humans ,In patient ,Endoscopic resection ,neoplasms ,Early Detection of Cancer ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Narrow-band imaging ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Head and neck cancer ,metachronous cancer ,Gastroenterology ,Neoplasms, Second Primary ,General Medicine ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,esophageal squamous cell carcinoma ,stomatognathic diseases ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,surveillance ,Carcinoma, Squamous Cell ,030211 gastroenterology & hepatology ,Female ,Metachronous cancer ,business ,Follow-Up Studies - Abstract
AIM To evaluate the clinical impact of surveillance for head and neck (HN) region with narrow band imaging (NBI) in patients with esophageal squamous cell carcinoma (ESCC). METHODS Since 2006, we introduced the surveillance for HN region using NBI for all patients with ESCC before treatment, and each follow-up. The patients with newly diagnosed stage I to III ESCC were enrolled and classified into two groups as follows: Group A (no surveillance for HN region); between 1992 and 2000), and Group B (surveillance for HN region with NBI; between 2006 and 2008). We comparatively evaluated the detection rate of superficial head and neck squamous cell carcinoma (HNSCC), and the serious events due to metachronous advanced HNSCC during the follow-up. RESULTS A total 561 patients (group A: 254, group B: 307) were enrolled. Synchronous superficial HNSCC was detected in 1 patient (0.3%) in group A, and in 12 (3.9%) in group B (P = 0.008). During the follow up period, metachronous HNSCC were detected in 10 patients (3.9%) in group A and in 30 patients (9.8%) in group B (P = 0.008). All metachronous lesions in group B were early stage, and 26 patients underwent local resection, however, 6 of 10 patients (60%) in group A lost their laryngeal function and died with metachronous HNSCC. CONCLUSION Surveillance for the HN region by using NBI endoscopy increase the detection rate of early HNSCC in patients with ESCC, and led to decrease serious events related to advanced metachronous HNSCC.
- Published
- 2017
45. Direct access to N-unprotected tetrasubstituted propargylamines via direct catalytic alkynylation of N-unprotected trifluoromethyl ketimines
- Author
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Kazuhiro Morisaki, Takashi Ohshima, and Hiroyuki Morimoto
- Subjects
Trifluoromethyl ,Primary (chemistry) ,010405 organic chemistry ,Metals and Alloys ,General Chemistry ,Diethylzinc ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,Alkynylation ,chemistry ,Materials Chemistry ,Ceramics and Composites ,Organic chemistry - Abstract
Direct catalytic alkynylation of N-unprotected trifluoromethyl ketimines is reported for the first time. A combination of catalytic amounts of diethylzinc and carboxylic acids promoted the reactions under proton-transfer conditions, allowing an unprecedented direct access to N-unprotected α-tetrasubstituted primary amines without additional deprotection steps.
- Published
- 2017
46. Synthesis of 1-Tetrasubstituted 2,2,2-Trifluoroethylamine Derivatives via Palladium-Catalyzed Allylation of sp3 C–H Bonds
- Author
-
Takashi Ohshima, Yuta Kondo, Hiroyuki Morimoto, Masanao Sawa, and Kazuhiro Morisaki
- Subjects
010405 organic chemistry ,Chemistry ,Trifluoroethylamine ,chemistry.chemical_element ,General Chemistry ,General Medicine ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,Stereocenter ,Drug Discovery ,Organic chemistry ,Carbon ,Palladium - Abstract
This note describes the construction of tetrasubstituted carbon stereocenters via palladium-catalyzed allylation of sp3 C-H bonds of 2,2,2-trifluoroethylamine derivatives. The presence of 2-pyridyl group of the imines derived from 1-substituted-2,2,2-trifluoroethylamine was key to promoting the reaction efficiently, allowing an access to a variety of 1-allylated 2,2,2-trifluoroethylamine derivatives with tetrasubstituted carbon stereocenters.
- Published
- 2017
47. PKR regulates LPS-induced osteoclast formation and bone destructionin vitroandin vivo
- Author
-
Jumpei Teramachi, Hirohiko Okamura, Di Yang, Hiroki Shinohara, Kazuhiko Ochiai, Toshihiko Nagata, Tatsuji Haneji, Yuji Inagaki, Hiroyuki Morimoto, and Ryoko Baba
- Subjects
Lipopolysaccharides ,0301 basic medicine ,MAPK/ERK pathway ,Indoles ,MAP Kinase Signaling System ,Alveolar Bone Loss ,Osteoclasts ,Cell Line ,Mice ,eIF-2 Kinase ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Osteogenesis ,Osteoclast ,medicine ,Animals ,Protein kinase A ,General Dentistry ,Porphyromonas gingivalis ,Periodontal Diseases ,EIF-2 kinase ,biology ,NF-kappa B ,030206 dentistry ,biology.organism_classification ,NFKB1 ,Protein kinase R ,Rats ,Cell biology ,Thiazoles ,030104 developmental biology ,medicine.anatomical_structure ,Otorhinolaryngology ,Immunology ,biology.protein ,lipids (amino acids, peptides, and proteins) - Abstract
Objective In this study, we aimed to clarify the precise mechanism underlying lipopolysaccharide (LPS)-induced osteoclastogenesis in periodontal disease with a special reference to double-stranded RNA-dependent protein kinase (PKR). Material and methods We dissected the role of PKR in LPS-induced osteoclast differentiation and function using primary mouse bone marrow cells and RAW264.7 pre-osteoclastic cell line. We used a rat experimental periodontitis (PD) model induced by ligature placement with a Porphyromonas gingivalis LPS injection (PD rat) and analyzed the therapeutic effects of C16, a PKR inhibitor, on bone loss in PD rats. Results Protein kinase is strongly upregulated and phosphorylated by LPS in the osteoclasts. The inhibition of PKR suppressed LPS-stimulated osteoclast formation and activation. PKR inhibition also suppressed the LPS-mediated activation of NF-κB and MAPK, which are critical pathways for osteoclastogenesis. High expressions of PKR were detected in osteoclasts of PD rats, and the treatment with C16 effectively prevented alveolar bone destruction in PD rats. Conclusions PKR plays a pivotal role in LPS-induced bone loss in PD and, thus, has potential as a therapeutic target for PD.
- Published
- 2016
48. Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells
- Author
-
Di Yang, Tatsuji Haneji, Hiroyuki Morimoto, Hirohiko Okamura, and Jumpei Teramachi
- Subjects
0301 basic medicine ,Apoptosis ,Biology ,environment and public health ,Pathology and Forensic Medicine ,Focal adhesion ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Protein Phosphatase 2 ,Viability assay ,Neoplasm Metastasis ,Cell Shape ,Molecular Biology ,Cell Proliferation ,Osteosarcoma ,Cell growth ,Cell Biology ,Cell cycle ,medicine.disease ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Signal transduction - Abstract
Osteosarcoma is the most frequent primary bone tumor. Serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction. In this study, we examined the expression and function of PP2A Cα in osteosarcoma cells. PP2A Cα expression was expected to be higher in malignant osteosarcoma tissues. PP2A Cα expression level and PP2A activity was higher in malignant osteosarcoma LM8 cells compared with that in primary osteoblasts and in the osteoblast-like cell line MC3T3-E1. Okadaic acid, an inhibitor of PP2A, reduced cell viability and induced apoptosis in LM8 cells. PP2A Cα-knockdown LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial structures than that in original LM8 cells. Focal adhesion kinase phosphorylation and NF-κB activity decreased in shPP2A-treated cells. Sensitivity to serum deprivation-induced apoptosis increased in shPP2A-treated cells, accompanied by a lower expression level of anti-apoptotic BCL-2 in these cells. Reduction of PP2A Cα resulted in a decrease in the migration ability of LM8 cells in vitro. Reduction in PP2A Cα levels in vivo suppressed proliferation and metastasis in LM8 cells. PP2A Cα expression was also higher in human osteosarcoma MG63 and SaOS-2 cells than that in primary osteoblasts and MC3T3-E1 cells, and reduction in PP2A Cα levels suppressed the cell proliferation rate and migration ability of MG63 cells. These results indicate that PP2A Cα has a critical role in the proliferation and metastasis of osteosarcoma cells; therefore, its inhibition could potentially suppress the malignancy of osteosarcoma cells.
- Published
- 2016
49. Skill-up study of systemic endoscopic examination technique using narrow band imaging of the head and neck region of patients with esophageal squamous cell carcinoma: Prospective multicenter study
- Author
-
Taketo Yamaguchi, Yoichi Yamamoto, Ayumi Okamura, Keisuke Kanda, Motoyasu Kan, Yuzo Toyama, Akira Nakano, Shigenobu Yoshimura, Rino Nankinzan, Kyoko Arahata, Naoki Okamoto, Shingo Kasamatsu, Hiroyuki Morimoto, Yuuka Watanabe, Shosuke Hosaka, and Tomonori Yano
- Subjects
Adult ,Male ,medicine.medical_specialty ,Esophageal Neoplasms ,Esophageal squamous cell carcinoma ,Group B ,03 medical and health sciences ,Narrow Band Imaging ,0302 clinical medicine ,medicine ,Examination technique ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Head and neck ,Aged ,Aged, 80 and over ,Narrow-band imaging ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Middle Aged ,medicine.disease ,Image Enhancement ,Head and neck squamous-cell carcinoma ,Endoscopy ,Multicenter study ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Radiology ,Clinical Competence ,Esophageal Squamous Cell Carcinoma ,Esophagoscopy ,business - Abstract
OBJECTIVE To evaluate the usefulness of a training program on endoscopic head and neck surveillance for beginner endoscopists. METHODS This prospective multicenter study included 13 beginner endoscopists from 10 institutions who received training in systematic observation techniques and diagnostic criteria, and the training involved hands-on learning. Between May 2016 and February 2017, enrolled patients with current or previously diagnosed esophageal squamous cell carcinomas underwent head and neck surveillance using narrow band imaging (NBI) endoscopy, and histologically confirmed head and neck squamous cell carcinoma (HNSCC) detection rates, endoscopic image quality, and examination times were compared before (group A) and after (group B) the training program. Maximum possible score for the endoscopic images was 30 points. RESULTS A total of 330 patients, comprising 181 in group A and 149 in group B, were enrolled. Three patients with HNSCC were detected in group A (1.7%) and in group B (2.0%; P = 1.000). Mean ± standard deviation (SD) examination times were 157 ± 71 s and 174 ± 109 s in groups A and B, respectively, (P = 0.073). Mean ± SD scores of the endoscopic images were 25.04 ± 5.47 points and 27.01 ± 4.35 points in groups A and B, respectively, (P
- Published
- 2019
50. 慢性一側性前庭機能障害患者における身体活動の客観的評価とめまいに関する障害,不安,姿勢安定能との関連性<要約>
- Author
-
Hiroyuki, Morimoto
- Abstract
平成30年度
- Published
- 2019
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