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Takeshi Yasuda, Wataru Kagawa, Tomoo Ogi, Takamitsu A Kato, Takehiro Suzuki, Naoshi Dohmae, Kazuya Takizawa, Yuka Nakazawa, Matthew D Genet, Mika Saotome, Michio Hama, Teruaki Konishi, Nakako Izumi Nakajima, Masaharu Hazawa, Masanori Tomita, Manabu Koike, Katsuko Noshiro, Kenichi Tomiyama, Chizuka Obara, Takaya Gotoh, Ayako Ui, Akira Fujimori, Fumiaki Nakayama, Fumio Hanaoka, Kaoru Sugasawa, Ryuichi Okayasu, Penny A Jeggo, Katsushi Tajima
The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis...
March 28, 2018: PLoS Genetics
Shinya Yokosaka, Akiko Izawa, Chizuka Sakai, Eri Sakurada, Yasuhiro Morita, Yukihiro Nishio
Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50  < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs...
May 1, 2018: Bioorganic & Medicinal Chemistry
Shinya Suzuki, Yuji Sugawara, Hideaki Inada, Riichiro Tsuji, Atsushi Inoue, Ryuji Tanimura, Rieko Shimozono, Mitsuhiro Konno, Tomofumi Ohyama, Eriko Higashi, Chizuka Sakai, Koji Kawai
κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor and peripheral selectivity are attractive targets in the development of drugs for pain. We have previously attempted to create novel analgesics with peripheral selective κ-opioid receptor agonist on the basis of TRK-820. In this study, we elucidated the biological properties of 17-hydroxy-cyclopropylmethyl and 10α-hydroxy derivatives. These compounds were found to have better κ-opioid receptor selectivity and peripheral selectivity than TRK-820...
2017: Chemical & Pharmaceutical Bulletin
Kenji Kanekiyo, Tamami Wakabayashi, Norihiko Nakano, Yoshihiro Yamada, Masahiro Tamachi, Yoshihisa Suzuki, Masatoshi Fukushima, Fukuki Saito, Seiya Abe, Chihiro Tsukagoshi, Chimi Miyamoto, Chizuka Ide
Bone marrow stromal cells (BMSCs) have been studied for the treatment of spinal cord injury (SCI). In previous studies, we showed that the transplantation of BMSCs, even though they disappeared from the host spinal cord within 1-3 weeks after transplantation, improved locomotor behaviors and promoted axonal regeneration. This result led to the hypothesis that BMSCs might release some neurotrophic factors effective for the treatment of SCI. The present study examined this by injecting the conditioned medium (CM) of BMSCs to treat SCI in rats...
February 1, 2018: Journal of Neurotrauma
Kenji Kanekiyo, Norihiko Nakano, Tamami Homma, Yoshihiro Yamada, Masahiro Tamachi, Yoshihisa Suzuki, Masanori Fukushima, Fukuki Saito, Chizuka Ide
The effects of multiple injection of bone marrow mononuclear cells (BMNCs) on spinal cord injury (SCI) were compared with those of single injection in rats. BMNCs separated by density-gradient centrifugation from a bone marrow perfusate were injected three times (once weekly) through the cerebrospinal fluid (CSF) via the fourth ventricle, and the locomotor improvement and tissue recovery, including axonal regeneration, were compared with those of single injection. While the single-injection group showed a steep elevation of the Basso-Beattie-Bresnahan (BBB) score 1 week after transplantation, the multiple-injection group maintained a similar steep elevation for 2 weeks after transplantation, and the BBB scores of the multiple-injection group remained thereafter at a level approximately 2-3 points higher than those of the single-injection group until the end of the experiment...
November 1, 2017: Journal of Neurotrauma
Yasutoshi Ando, Shinichiro Saito, Nami Yamanaka, Chizuka Suzuki, Takahiro Ono, Noriko Osaki, Yoshihisa Katsuragi
Consumption of alpha linolenic acid-enriched diacylglycerol (ALA-DAG) reduces visceral fat area. In this study, we performed a randomized, placebo-controlled, double-blind, crossover intervention trial to investigate the effect of ALA-DAG on dietary fat oxidation in comparison with control triacylglycerol (TAG). Each subject (n=16) consumed either 2.5 g/d of ALA-DAG or TAG for 14-d, separated by a 21-d washout period. At the end of each consumption period, we assessed dietary fat oxidation. ALA-DAG consumption significantly enhanced dietary fat utilization as energy compared to TAG consumption...
2017: Journal of Oleo Science
Chizuka Ide, Norihiko Nakano, Kenji Kanekiyo
Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices...
September 2016: Neural Regeneration Research
Masaharu Hazawa, Takeshi Yasuda, Ai Saotome-Nakamura, Kenichi Tomiyama, Chizuka Obara, Takaya Goto, Katsushi Tajima
Plasminogen activator inhibitor-1 (PAI-1) is induced by radiation resulting in endothelial cell impairment, potentially leading to multiple organ failure. Vitronectin (VN) is a 75-kDa glycoprotein (VN75 ) cleaved into two forms (VN75 or VN65/10 ) by furin, which is regulated by intracellular PAI-1. VN protects against radiation-induced endothelial cell death, but the mechanisms involved in VN processing and its interactions with intra- and extracellular PAI-1 remain unclear. We examined these processes in cells in vitro using recombinant proteins or overexpression of VN and PAI-1 genes, including furin-susceptible (T381 ) and furin-resistant VN (A381 )...
December 2016: Vascular Pharmacology
Chizuka Obara, Kazuya Takizawa, Kenichi Tomiyama, Masaharu Hazawa, Ai Saotome-Nakamura, Takaya Gotoh, Takeshi Yasuda, Katsushi Tajima
The generation of induced-pluripotential stem cells- (iPSCs-) derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. The present study compared molecular properties and differentiation potential of derived mouse iPS-MSCs by deriving on gelatin or collagen-coated surfaces...
2016: Stem Cells International
Chizuka Ide, Kenji Kanekiyo
Transplantation of somatic cells, including bone marrow stromal cells (BMSCs), bone marrow mononuclear cells (BMNCs), and choroid plexus epithelial cells (CPECs), enhances the outgrowth of regenerating axons and promotes locomotor improvements. They are not integrated into the host spinal cord, but disappear within 2-3 weeks after transplantation. Regenerating axons extend at the spinal cord lesion through the astrocyte-devoid area that is filled with connective tissue matrices. Regenerating axons have characteristics of peripheral nerves: they are associated with Schwann cells, and embedded in connective tissue matrices...
July 2016: Neural Regeneration Research
Chizuka Sakai, Shunsuke Iwano, Makiko Shimizu, Jun Onodera, Masashi Uchida, Eri Sakurada, Yuri Yamazaki, Yoshiji Asaoka, Naoko Imura, Yasuhiro Uno, Norie Murayama, Ryoji Hayashi, Hiroshi Yamazaki, Yohei Miyamoto
The microminipig is one of the smallest minipigs that has emerged as a possible experimental animal model, because it shares many anatomical and/or physiological similarities with humans, including the coronary artery distribution in the heart, the digestive physiology, the kidney size and its structure, and so on. However, information on gene expression profiles, including those on drug-metabolizing phase I and II enzymes, in the microminipig is limited. Therefore, the aim of the present study was to identify transcripts in microminipig livers and to determine gene expression profiles...
May 2016: Biopharmaceutics & Drug Disposition
Norihiko Nakano, Kenji Kanekiyo, Takatoshi Nakagawa, Michio Asahi, Chizuka Ide
NTAK (neural- and thymus-derived activator for ErbB kinases), also known as neuregulin-2 (NRG2), is a member of the epidermal growth factor (EGF) family, which binds directly to ErbB3 and ErbB4, and transactivates ErbB2. NTAK/NRG2 is structurally homologous to NRG1. The biological function of NTAK/NRG2 still remains unknown, especially in the nervous system, whereas NRG1 is known to be essential for nervous system function. In the present study, we examined the functions of NTAK/NRG2 secreted from astrocytes to neurons...
May 27, 2016: Neuroscience Letters
Chizuka Obara, Ken-Ichi Tomiyama, Kazuya Takizawa, Rafiqul Islam, Takeshi Yasuda, Takaya Gotoh, Katsushi Tajima
Three-dimensional (3-D) aggregate culturing is useful for investigating the functional properties of mesenchymal stem/stromal cells (MSCs). For 3-D MSC analysis, however, pre-expansion of MSCs with two-dimensional (2-D) monolayer culturing must first be performed, which might abolish their endogenous properties. To avoid the need for 2-D expansion, we used prospectively isolated mouse bone marrow (BM)-MSCs and examined the differences in the biological properties of 2-D and 3-D MSC cultures. The BM-MSCs self-assembled into aggregates on nanoculture plates (NCP) that have nanoimprinted patterns with a low-cellular binding texture...
October 2016: Cell and Tissue Research
Yayoi Ando, Akira Hangaishi, Makoto Saika, Aki Chizuka, Michiko Kida, Kensuke Usuki
Since the long-term safety profile of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) therapy has not been well characterized, we investigated renal impairment in 50 CML patients treated with TKI in our institute. During the median follow up period of 63 months, 29% of patients developed chronic kidney disease (CKD). Although the glomerular filtration rate (GFR) gradually declined, it dropped most markedly in the first 2 years after starting TKI. The CKD incidence was higher in patients older than 40 years or with decreased GFR, hypertension, or dyslipidemia at baseline...
March 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Kenji Kanekiyo, Norihiko Nakano, Toru Noda, Yoshihiro Yamada, Yoshihisa Suzuki, Masayoshi Ohta, Atsushi Yokota, Masanori Fukushima, Chizuka Ide
PURPOSE: The effect of the transplantation of choroid plexus epithelial cells (CPECs) on locomotor improvement and tissue repair including axonal extension in spinal cord lesions was examined in rats with spinal cord injury (SCI). METHODS: CPECs were cultured from the choroid plexus of green fluorescent protein (GFP)-transgenic rats, and transplanted directly into the contusion-injured spinal cord lesions of rats of the same strain. Locomotor behaviors were evaluated based on BBB scores every week after transplantation until 4 weeks after transplantation...
February 24, 2016: Restorative Neurology and Neuroscience
Satomi Ueda, Shunichi Miyamoto, Kosuke Kaida, Aki Chizuka, Rie Kojima, Junichiro Takano, Toshie Ogasawara, Ko Miyamoto, Shigesaburo Miyakoshi, Yoshinobu Kanda
The safety and efficacy of treatment with liposomal amphotericin B (L-AMB) in elderly patients has not been clarified, especially in Japanese patients. Therefore, we retrospectively analyzed 33 elderly patients with hematological diseases of at least 65 years old who received L-AMB between 2009 and 2012. Their clinical outcomes were compared to those of 21 patients who were younger than 65 years. L-AMB was administered for empirical therapy (n = 2) or target therapy for possible (n = 14) or probable/proven (n = 17) invasive fungal infection...
May 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Yayoi Ando, Michiko Kida, Makoto Saika, Aki Chizuka, Akira Hangaishi, Akio Urabe, Kensuke Usuki
We report a 37-year-old pregnant woman with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab. She had been diagnosed with PNH-aplastic anemia at age 19 years, and started to receive eculizumab at age 35 years. Thereafter, she had no hemolytic attacks. She became pregnant 2 years later, and treatment with eculizumab was continued. During her pregnancy, she showed no exacerbation of hemolysis. She delivered a girl by Caesarean section at 37 weeks and 3 days of gestation. Postpartum, anticoagulant therapy was started...
November 2014: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Katsushi Tajima, Hidekazu Nishimura, Seiji Hongo, Masaharu Hazawa, A I Saotome-Nakamura, Kenichi Tomiyama, Chizuka Obara, Takeo Kato
Measles among healthcare workers (HCWs) is associated with a significant risk of nosocomial transmission to susceptible patients. When a measles case occurs in the healthcare setting, most guidelines recommend exhaustive measures. To evaluate the effects of measures against measles transmission in the healthcare setting precisely, it is essential to determine whether secondary transmission generally occurs. This study describes, for the first time, the actual secondary transmission rate for a measles-infected HCW in a ward with no special air ventilation capacity...
July 2014: International Journal of Infectious Diseases: IJID
Yoshihisa Suzuki, Namiko Ishikawa, Kaoru Omae, Tatsuya Hirai, Katsunori Ohnishi, Norihiko Nakano, Hidetaka Nishida, Toshio Nakatani, Masanori Fukushima, Chizuka Ide
PURPOSE: This study was conducted to assess the safety and feasibility of intrathecal transplantation of autologous bone marrow-derived mononuclear cells for the treatment of patients with spinal cord injury. METHODS: Ten patients were included in the study. Approximately 120 ml of bone marrow aspirate was obtained from bilateral iliac bone of patients with spinal cord injury. Isolation of mononuclear cells was performed using Ficoll density-gradient centrifugation...
2014: Restorative Neurology and Neuroscience
Masaharu Hazawa, Kenichi Tomiyama, Ai Saotome-Nakamura, Chizuka Obara, Takeshi Yasuda, Takaya Gotoh, Izumi Tanaka, Haruko Yakumaru, Hiroshi Ishihara, Katsushi Tajima
Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome-cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC...
April 18, 2014: Biochemical and Biophysical Research Communications
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