12 results on '"Onodera, Masafumi"'
Search Results
2. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization.
- Author
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Ichida, Yu, Utsunomiya, Yuko, and Onodera, Masafumi
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ZINC-finger proteins , *GENE silencing , *MOUSE leukemia viruses , *PROTEIN expression , *BINDING sites , *HISTONES - Abstract
Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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3. The third to fifth zinc fingers play an essential role in the binding of ZFP809 to the MLV-derived PBS.
- Author
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Ichida, Yu, Utsunomiya, Yuko, and Onodera, Masafumi
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KRUPPEL-like factors , *ZINC-finger proteins , *NUCLEOTIDE sequence , *PROTEIN expression , *EPIGENETICS - Abstract
Members of the kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family mediate a number of cellular processes through binding to target DNA sequences via zinc fingers. Generally, zinc fingers recognize three-nucleotide sequences; however, this rule is not universally applicable. Zinc finger protein 809 (ZFP809) belongs to the KRAB-ZFP family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV) via sequence-specific binding to the primer-binding site (PBS) located downstream of the MoMLV-long terminal repeat (LTR) and the induction of epigenetic modifications at LTR, such as repressive histone modifications and de novo DNA methylation. Previously, we demonstrated the role of the first to fifth zinc fingers of ZFP809 in binding to MLV PBS, indicating these zinc fingers do not recognize MLV PBS as a three-nucleotide sequence. Therefore, in the present study, we constructed truncated and mutated zinc fingers and examined their ability to bind to MLV PBS. The third to fifth zinc fingers of ZFP809 were found to be essential for binding to MLV PBS. Furthermore, the results of the present study indicate that other zinc fingers, which were not directly involved in binding to MLV PBS, may function in potentiating binding and stable protein expression. Further characterization of the amino acid sequences of zinc fingers will help further elucidate the functions and features of KRAB-ZFP and other zinc finger proteins. [ABSTRACT FROM AUTHOR]
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- 2016
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4. Augmentation of antitubercular therapy with IFNγ in a patient with dominant partial IFNγ receptor 1 deficiency.
- Author
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Takeda, Kanako, Kawai, Toshinao, Nakazawa, Yumiko, Komuro, Hisako, Shoji, Kensuke, Morita, Kumiko, Katsuta, Tomohiro, Yamamoto, Matsuri, Miyairi, Isao, Ohya, Yukihiro, Ishiguro, Akira, and Onodera, Masafumi
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ANTITUBERCULAR agents , *THERAPEUTIC use of interferons , *INTERFERON receptors , *OSTEOMYELITIS , *MYCOBACTERIUM bovis , *BCG vaccines - Abstract
Abstract: Osteomyelitis due to Mycobacterium bovis Bacille Calmette–Guerin (BCG) often develops in patients with interferon-γ receptor 1 (IFNγR1) deficiency. In these patients, susceptibility appears to be caused by impaired interleukin-12- and IFNγ-mediated immunity. Here we report the case of a one-year-old girl with dominant partial IFNγR1 deficiency who suffered from lymphadenitis and multiple sites of osteomyelitis due to BCG infection. She was allergic to isoniazid and rifampicin – the prescribed standard treatment – and required prior desensitization therapy. She was subsequently treated with these drugs, but her symptoms did not improve. IFNγ therapy was added to the antitubercular therapy, increasing the serum level of IFNγ and leading to the resolution of the lymphadenitis and osteomyelitis. In conclusion, high dose IFNγ therapy in combination with antitubercular drugs led to resolution of BCG infection in a patient with dominant partial IFNγ deficiency. [Copyright &y& Elsevier]
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- 2014
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5. Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method.
- Author
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Hamanaka, Sanae, Ooehara, Jun, Morita, Yohei, Ema, Hideo, Takahashi, Satoru, Miyawaki, Atsushi, Otsu, Makoto, Yamaguchi, Tomoyuki, Onodera, Masafumi, and Nakauchi, Hiromitsu
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TRANSGENIC mice , *GENE expression , *ERYTHROCYTES , *BLOOD platelets , *CELL lines , *LABORATORY mice , *VIRAL integration (Genetics) - Abstract
Highlights: [•] We have generated KuO transgenic mouse line by random segregation of provirus method. [•] KuO transgenic mouse line cells carry only one proviral integration site. [•] KuO transgenic mouse line cells stably express KuO in erythrocytes and platelets. [ABSTRACT FROM AUTHOR]
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- 2013
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6. Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease.
- Author
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Kawai, Toshinao, Watanabe, Nobuyuki, Yokoyama, Midori, Arai, Katsuhiro, Oana, Shinji, Harayama, Shizuko, Yasui, Kozo, Oh-ishi, Tsutomu, and Onodera, Masafumi
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THALIDOMIDE , *INFLAMMATION , *LIPOPOLYSACCHARIDES , *CYTOKINES , *CHRONIC granulomatous disease , *GENETIC disorders - Abstract
Abstract: Chronic granulomatous disease (CGD) is a rare inherited disorder characterized by an inability to produce reactive oxygen species, resulting in recurrent life-threatening infections. Curiously, half of the patients with CGD suffer from aseptic bowel inflammation (CGD colitis) due to dysregulated inflammation induced by TNF-α and IL-1β. Thus, developing therapies that regulate excessive inflammatory responses without interrupting antimicrobial immunity would benefit CGD colitis patients. Here, we show that thalidomide suppressed TNF-α-induced NF-κB activation and ATP-induced IL-1β secretion, but did not interrupt the production of IL-1β, IL-6, IL-8, and TNF-α in response to lipopolysaccharide in CGD monocytes. We report on a CGD colitis patient that showed decreased bowel inflammation characterized by reduced serum levels of inflammatory cytokines without evidence of progression of fungal and bacterial infections present at initiation of thalidomide therapy. Our results suggest that thalidomide could be an efficacious therapeutic option for patients with CGD colitis suffering from serious infections. [Copyright &y& Elsevier]
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- 2013
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7. Growth promotion of genetically modified hematopoietic progenitors using an antibody/c-Mpl chimera
- Author
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Kawahara, Masahiro, Chen, Jianhong, Sogo, Takahiro, Teng, Jinying, Otsu, Makoto, Onodera, Masafumi, Nakauchi, Hiromitsu, Ueda, Hiroshi, and Nagamune, Teruyuki
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THROMBOPOIETIN , *HEMATOPOIETIC stem cells , *CHIMERISM , *CELL proliferation , *CELL receptors , *CELLULAR signal transduction , *CYTOKINES , *IMMUNOGLOBULINS - Abstract
Abstract: Thrombopoietin is a potent cytokine that exerts proliferation of hematopoietic stem cells (HSCs) through its cognate receptor, c-Mpl. Therefore, mimicry of c-Mpl signaling by a receptor recognizing an artificial ligand would be attractive to attain specific expansion of genetically modified HSCs. Here we propose a system enabling selective expansion of genetically modified cells using an antibody/receptor chimera that can be activated by a specific antigen. We constructed an antibody/c-Mpl chimera, in which single-chain Fv (ScFv) of an anti-fluorescein antibody was tethered to the extracellular D2 domain of the erythropoietin receptor and transmembrane/cytoplasmic domains of c-Mpl. When the chimera was expressed in interleukin (IL)-3-dependent pro-B cell line Ba/F3, genetically modified cells were selectively expanded in the presence of fluorescein-conjugated BSA (BSA-FL) as a specific antigen. Furthermore, highly purified mouse HSCs transduced with the retrovirus carrying antibody/c-Mpl chimera gene proliferated in vitro in response to BSA-FL, and the cells retained in vivo long-term repopulating abilities. These results demonstrate that the antibody/c-Mpl chimera is capable of signal transduction that mimics wild-type c-Mpl signaling. [Copyright &y& Elsevier]
- Published
- 2011
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8. T cell growth control using hapten-specific antibody/interleukin-2 receptor chimera
- Author
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Sogo, Takahiro, Kawahara, Masahiro, Ueda, Hiroshi, Otsu, Makoto, Onodera, Masafumi, Nakauchi, Hiromitsu, and Nagamune, Teruyuki
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T cells , *REGULATION of cell growth , *HAPTENS , *IMMUNOGLOBULINS , *INTERLEUKIN-2 , *MOSAICISM , *CANCER immunotherapy - Abstract
Abstract: IL-2 is a cytokine that is essential for the expansion and survival of activated T cells. Although adoptive transfer of tumor-specific T cells with IL-2 is one of strategies for cancer immunotherapy, it is essential to replace IL-2 that exerts severe side effects in vivo. To solve this problem, we propose to use an antibody/IL-2R chimera, which can transduce a growth signal in response to a cognate antigen. We constructed two chimeras, in which ScFv of anti-fluorescein antibody was tethered to extracellular D2 domain of erythropoietin receptor and transmembrane/cytoplasmic domains of IL-2Rβ or γ chain. When the chimeras were co-expressed in IL-3-dependent pro-B cell line Ba/F3 and IL-2-dependent T cell line CTLL-2, gene-modified cells were selectively expanded in the absence of IL-3 and IL-2, respectively, by adding fluorescein-conjugated BSA (BSA-FL) as a cognate antigen. Growth assay revealed that the cells with the chimeras transduced a growth signal in a BSA-FL dose-dependent manner. Furthermore, STAT3, STAT5, ERK1/2 and Akt, which are hallmarks for IL-2R signaling, were all activated by the chimeras in CTLL-2 transfectant. We also demonstrated that the chimeras were functional in murine primary T cells. These results demonstrate that the antibody/IL-2R chimeras could substantially mimic the wild-type IL-2R and could specifically expand gene-modified T cells in the presence of the cognate antigen. [Copyright &y& Elsevier]
- Published
- 2009
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9. Effects of enzyme replacement therapy on immune function in ADA deficiency patient.
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Nakazawa, Yumiko, Kawai, Toshinao, Uchiyama, Toru, Goto, Fumihiro, Watanabe, Nobuyuki, Maekawa, Takanobu, Ishiguro, Akira, Okuyama, Torayuki, Otsu, Makoto, Yamada, Masafumi, Hershfield, Michael S., Ariga, Tadashi, and Onodera, Masafumi
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ADENOSINE deaminase deficiency , *STEM cell transplantation , *HLA histocompatibility antigens , *APPETITE loss , *MEDICAL protocols , *THERAPEUTICS - Published
- 2015
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10. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells
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Oka, Naoki, Soeda, Akio, Inagaki, Akihito, Onodera, Masafumi, Maruyama, Hidekazu, Hara, Akira, Kunisada, Takahiro, Mori, Hideki, and Iwama, Toru
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STEM cells , *BRAIN tumors , *NEOVASCULARIZATION , *CARCINOGENESIS - Abstract
Abstract: There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche. [Copyright &y& Elsevier]
- Published
- 2007
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11. Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells
- Author
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Uchiyama, Toru, Kumaki, Satoru, Ishikawa, Yoshinori, Onodera, Masafumi, Sato, Miki, Du, Wei, Sasahara, Yoji, Tanaka, Nobuyuki, Sugamura, Kazuo, and Tsuchiya, Shigeru
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CELLS , *GENE therapy , *GENETIC engineering , *T cells , *CELL lines , *BIOMEDICAL transducers , *MICROBIAL genetics , *BACTERIOPHAGES , *HERPES simplex virus , *THYMIDINE , *ANTIVIRAL agents , *GENETIC mutation , *CELL proliferation , *FEASIBILITY studies - Abstract
Abstract: Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human γc chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the γc chain, the cells were treated with ganciclovir (GCV). The γc chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the γc chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial. [Copyright &y& Elsevier]
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- 2006
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12. X-linked inhibitor of apoptosis protein deficiency complicated with Crohn's disease-like enterocolitis and Takayasu arteritis: A case report.
- Author
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Takeuchi, Ichiro, Kawai, Toshinao, Nambu, Meika, Migita, Ohsuke, Yoshimura, Satoshi, Nishimura, Kenichi, Yoshioka, Takako, Ogura, Masao, Kyodo, Reiko, Shimizu, Hirotaka, Ito, Shuichi, Kato, Motohiro, Onodera, Masafumi, Hata, Kenichiro, Matsubara, Yoichi, and Arai, Katsuhiro
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TAKAYASU arteritis , *INFLAMMATORY bowel diseases , *ENTEROCOLITIS , *PROTEIN deficiency , *CROHN'S disease - Abstract
X-linked inhibitor of apoptosis protein (XIAP) deficiency results in monogenic inflammatory bowel disease. To date, no vasculitis associated with XIAP deficiency has been reported. A 10-year-old boy was diagnosed with Crohn's disease and he responded poorly to conventional treatment for Crohn's disease. He was dependent on corticosteroids and parenteral nutrition. To manage severe colitis, he underwent ileostomy followed by ileocolectomy for an ileo-sigmoid fistula. At the age of 15 years, he developed IgA vasculitis and at the age of 17 years, he developed refractory Takayasu arteritis (TAK), which was resistant to corticosteroid and immunosuppressive therapy. Whole-exome sequencing revealed a novel mutation of the splice acceptor site in XIAP (c.1057-1G > A) at the age of 19 years. Allogeneic hematopoietic stem cell transplantation was successful with subsequent withdrawal of intensive immunosuppressive therapy and clinical remission of both enterocolitis and TAK. This case suggests that patients with XIAP deficiency could develop intractable inflammatory disease involving the intestinal tract and blood vessels. • We report the first case of XIAP deficiency with Crohn's-like enterocolitis and TAK. • A novel single nucleotide variant of XIAP was detected. • Allo-HSCT is effective for enterocolitis and arteritis. [ABSTRACT FROM AUTHOR]
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- 2020
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