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268 results on '"Osaki, H."'

1. Investigation of the leukaemic activity of MLL-fusions in human haematopoietic cells

Author

Osaki, H.

Subjects
616.99
Abstract

The mixed lineage leukaemia (MLL) gene is frequently the target of chromosomal translocation in infant leukaemia. Translocation results in an in-frame chimeric fusion gene which is implicated in both ALL and AML, with particularly poor prognoses. It is widely accepted that MLL has a crucial role in regulating haematopoiesis. Our lab has previously developed a murine model for conditional expression of MLL-fusions to establish a list of transcriptional target genes using Affymetrix GeneChip analysis. In order to study the role of MLL-fusion target genes in human leukaemia cells, we generated four independent immortalised myeloid cell lines from human cord blood, using the MLL-AF9 fusion, by means of lentiviral transduction. The transduced cells proliferated exponentially in liquid culture and were found to cause leukaemia upon xenotransplantation into immunodeficient mice. One of the target genes up-regulated by the MLL-fusions, RUVBL2, encodes an ATPase belonging to AAA+ family that has multiple roles in telomerase and chromatin-remodelling complexes. In this study, we demonstrate that RUVBL2 is also up-regulated by MLL-AF9 in human immortalised myeloid cells. shRNA knock down of RUVBL2 expression in these cells, and in the human leukaemia cell line THP-1, results in decreased cell proliferation and clonogenic potential, accompanied by an increase in apoptosis and differentiation, as judged by CD15 expression. Furthermore, inhibition of RUVBL2 expression in THP-1 cells leads to a reduction in hTERT mRNA expression and telomerase activity. Together, these data demonstrate the requirement of RUVBL2 to mediate MLL-fusion induced telomerase activity in human cells, and suggest the possibility of targeting RUVBL2 as a potential therapeutic strategy for MLL-fusion associated leukaemia.

Published
2011

3. The clinical effectiveness of tafluprost on Japanese normal-tension glaucoma patients

Author

Nomura A, Osaki H, Shimada F, and Kuwayama Y

Subjects
MD slope, NTG, Observational post-marketing study, Ophthalmology, Visual field, RE1-994
Abstract

Akio Nomura,1 Hirotaka Osaki,1 Fumiki Shimada,1 Yasuaki Kuwayama2 1Pharmacovigilance, Quality Compliance Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan; 2Fukushima Eye Clinic, Osaka, Japan Purpose: This study evaluates the effect of tafluprost on visual field progression in normal-tension glaucoma (NTG) in a Japanese population under daily clinical practice settings.Patients and methods: This is a post-marketing, multicenter, non-interventional, observational study. Patients with NTG who initiated tafluprost treatment were registered and prospectively observed for 2–3 years to investigate its effectiveness on visual field progression and intraocular pressure (IOP) and safety in Japan. Visual field progression was evaluated using mean deviation (MD) slopes in a visual field analysis set that comprised patients with reliable Humphrey visual fields taken at 5 or more time points throughout the 2–3 years.Results: Of the 1,454 patients registered from 160 medical institutions, 1,353 were set for safety analysis and 416 were set for visual field analysis. Due to insufficient effectiveness or safety reasons 194 patients discontinued tafluprost, and 388 patients discontinued tafluprost due to being lost to follow-up or another reason. The MD slopes were −0.09±0.85 dB/year in the entire visual field analysis set, -0.02±0.80 dB/year in naïve monotherapy patients, −0.07±0.68 dB/year in switching monotherapy patients, and −0.32±1.04 dB/year in concomitant therapy patients. In naïve monotherapy, a significant difference in MD slopes was observed between patients with an IOP reduction of 10% or higher (0.11±0.73 dB/year) vs patients with an IOP reduction of

Published
2018

4. ICTV virus taxonomy profile: Yadokariviridae 2023

Author

Sato, Y, Das, S, Velasco, L, Turina, M, Osaki, H, Kotta-Loizou, I, Coutts, RHA, Kondo, H, Sabanadzovic, S, Suzuki, N, and Ictv Report Consortium

Subjects
Virology
Abstract

The family Yadokariviridae, with the genera Alphayadokarivirus and Betayadokarivirus, includes capsidless non-segmented positive-sense (+) RNA viruses that hijack capsids from phylogenetically distant double-stranded RNA viruses. Yadokarivirids likely replicate inside the hijacked heterocapsids using their own RNA-directed RNA polymerase, mimicking dsRNA viruses despite their phylogenetic placement in a (+) RNA virus lineage. Yadokarivirids can have negative or positive impacts on their host fungi, through interactions with the capsid donor dsRNA viruses. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Yadokariviridae, which is available at ictv.global/report/yadokariviridae.

Published
2022

7. Genomic imprinting drives eusociality

Author

Hiromu Ito, Kazuya Kobayashi, Osaki H, Jin Yoshimura, Edward L. Vargo, and Kenji Matsuura

Subjects
Natural selection, Evolution of eusociality, Transgenerational epigenetics, Evolutionary biology, Mechanism (biology), Kin selection, Reproductive capacity, Biology, Genomic imprinting, Eusociality
Abstract

The origin of eusociality, altruistically foregoing personal reproduction to help others, has been a long-standing paradox ever since Darwin. Most eusocial insects and rodents likely evolved from subsocial precursors, in which older offspring “helpers” contribute to the development of younger siblings without a permanent sterile caste. The driving mechanism for the transition from subsociality (with helpers) to eusociality (with lifelong sterile workers) remains an enigma because individuals in subsocial groups are subject to direct natural selection rather than kin selection. Our genomic imprinting theory demonstrates that natural selection generates eusociality in subsocial groups when parental reproductive capacity is linked to a delay in the sexual development of offspring due to sex-antagonistic action of transgenerational epigenetic marks. Focusing on termites, our theory provides the missing evolutionary link to explain the evolution of eusociality from their subsocial wood-feeding cockroach ancestors, and provides a novel framework for understanding the origin of eusociality.

Published
2021

16. Using discrete choice experiments to inform the design of complex interventions

Author

Terris-Prestholt, F, Neke, N, Grund, JM, Plotkin, M, Kuringe, E, Osaki, H, Ong, JJ, Tucker, JD, Mshana, G, Mahler, H, Weiss, HA, Wambura, M, Terris-Prestholt, F, Neke, N, Grund, JM, Plotkin, M, Kuringe, E, Osaki, H, Ong, JJ, Tucker, JD, Mshana, G, Mahler, H, Weiss, HA, and Wambura, M

Abstract

BACKGROUND: Complex health interventions must incorporate user preferences to maximize their potential effectiveness. Discrete choice experiments (DCEs) quantify the strength of user preferences and identify preference heterogeneity across users. We present the process of using a DCE to supplement conventional qualitative formative research in the design of a demand creation intervention for voluntary medical male circumcision (VMMC) to prevent HIV in Tanzania. METHODS: The VMMC intervention was designed within a 3-month formative phase. In-depth interviews (n = 30) and participatory group discussions (n = 20) sought to identify broad setting-specific barriers to and facilitators of VMMC among adult men. Qualitative results informed the DCE development, identifying the role of female partners, service providers' attitudes and social stigma. A DCE among 325 men in Njombe and Tabora, Tanzania, subsequently measured preferences for modifiable VMMC service characteristics. The final VMMC demand creation intervention design drew jointly on the qualitative and DCE findings. RESULTS: While the qualitative research informed the community mobilization intervention, the DCE guided the specific VMMC service configuration. The significant positive utilities (u) for availability of partner counselling (u = 0.43, p < 0.01) and age-separated waiting areas (u = 0.21, p < 0.05) led to the provision of community information booths for partners and provision of age-separated waiting areas. The strong disutility of female healthcare providers (u = - 0.24, p < 0.01) led to re-training all providers on client-friendliness. CONCLUSION: This is, to our knowledge, the first study documenting how user preferences from DCEs can directly inform the design of a complex intervention. The use of DCEs as formative research may help increase user uptake and adherence to complex interventions.

Published
2019

19. A proposal to extend the ICRF to higher frequencies

Author

Resch, G. M, Jacobs, C, Jones, D, Lanyi, G, Lowe, S, Naudet, C, Steppe, A, Zhang, L, Ulvestad, J, Taylor, G, Sovers, O, Ma, C, Gordon, D, Fey, A, Boboltz, D, Charlot, P, Kondo, T, Koyama, Y, Nakajima, J, Sekido, M, Ichikawa, R, Kawai, E, Osaki, H, Okuno, H, and Kimura, M

Published
2002

20. A proposal to extend the ICRF to multiple frequencies

Author

REsch, G. M, Jacobs, D, Jones, D, Lanyi, G, Lowe, S, Naudet, C, Steppe, A, Zhang, L, Ulvestad, J, Taylor, G, Sovers, O, Ma, C, Gordon, D, Fey, A, Boboltz, D, Charlot, P, Kondo, T, Koyama, Y, Nakajima, J, Sekido, M, Ichikawa, R, Kawai, E, Osaki, H, Okubo, H, and Kimura, M

Published
2001

21. DMD CLINICAL THERAPIES II

Author

Clemens, P., primary, Rao, V., additional, Connolly, A., additional, Harper, A., additional, Mah, J., additional, Smith, E., additional, McDonald, C., additional, Morgenroth, L., additional, Osaki, H., additional, and Hoffman, E., additional

Published
2018
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22. Measurement of the intrinsic bond strength of brittle thin films on flexible substrates

Author

Guo, Q, Keer, L. M, Osaki, H, and Wheeler, D. R

Subjects
Solid-State Physics
Abstract

The brittle cracking and subsequent debonding of nickel films deposited on polymer substrates subjected to uniaxial strain is investigated. Stress analyses for a film/substrate system are performed. Based on the analysis, the interfacial bond strength between brittle thin films and flexible substrates can be evaluated in terms of the tensile strength of the coating and the length of the largest segment that first debonds. Experiments were performed on Ni films with different thicknesses evaporated on polyethylene terephthalate substrates and the intrinsic bond strength was evaluated. The interfacial bond strengths were shown to be relatively independent of the film thickness for the range studied.

Published
1990
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24. Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia

Author

Dawson, MA, Gudgin, EJ, Horton, SJ, Giotopoulos, G, Meduri, E, Robson, S, Cannizzaro, E, Osaki, H, Wiese, M, Putwain, S, Fong, CY, Grove, C, Craig, J, Dittmann, A, Lugo, D, Jeffrey, P, Drewes, G, Lee, K, Bullinger, L, Prinjha, RK, Kouzarides, T, Vassiliou, GS, Huntly, BJP, Dawson, MA, Gudgin, EJ, Horton, SJ, Giotopoulos, G, Meduri, E, Robson, S, Cannizzaro, E, Osaki, H, Wiese, M, Putwain, S, Fong, CY, Grove, C, Craig, J, Dittmann, A, Lugo, D, Jeffrey, P, Drewes, G, Lee, K, Bullinger, L, Prinjha, RK, Kouzarides, T, Vassiliou, GS, and Huntly, BJP

Abstract

Recent evidence suggests that inhibition of bromodomain and extra-terminal (BET) epigenetic readers may have clinical utility against acute myeloid leukemia (AML). Here we validate this hypothesis, demonstrating the efficacy of the BET inhibitor I-BET151 across a variety of AML subtypes driven by disparate mutations. We demonstrate that a common 'core' transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment. This program is enriched for genes that contain 'super-enhancers', recently described regulatory elements postulated to control key oncogenic driver genes. Moreover, our program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response. We focus AML with mutations of the Nucleophosmin gene (NPM1) and show evidence to suggest that wild-type NPM1 has an inhibitory influence on BRD4 that is relieved upon NPM1c mutation and cytosplasmic dislocation. This leads to the upregulation of the core transcriptional program facilitating leukemia development. This program is abrogated by I-BET therapy and by nuclear restoration of NPM1. Finally, we demonstrate the efficacy of I-BET151 in a unique murine model and in primary patient samples of NPM1c AML. Taken together, our data support the use of BET inhibitors in clinical trials in AML.

Published
2014

26. Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia

Author

Dawson, M A, primary, Gudgin, E J, additional, Horton, S J, additional, Giotopoulos, G, additional, Meduri, E, additional, Robson, S, additional, Cannizzaro, E, additional, Osaki, H, additional, Wiese, M, additional, Putwain, S, additional, Fong, C Y, additional, Grove, C, additional, Craig, J, additional, Dittmann, A, additional, Lugo, D, additional, Jeffrey, P, additional, Drewes, G, additional, Lee, K, additional, Bullinger, L, additional, Prinjha, R K, additional, Kouzarides, T, additional, Vassiliou, G S, additional, and Huntly, B J P, additional

Published
2013
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36. A Reovirus Causes Hypovirulence of Rosellinia necatrix

Author

Kanematsu, S., primary, Arakawa, M., additional, Oikawa, Y., additional, Onoue, M., additional, Osaki, H., additional, Nakamura, H., additional, Ikeda, K., additional, Kuga-Uetake, Y., additional, Nitta, H., additional, Sasaki, A., additional, Suzaki, K., additional, Yoshida, K., additional, and Matsumoto, N., additional

Published
2004
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47. The AAA+ ATPase RUVBL2 is a critical mediator of MLL-AF9 oncogenesis.

Author

Osaki, H, Walf-Vorderwülbecke, V, Mangolini, M, Zhao, L, Horton, S J, Morrone, G, Schuringa, J J, de Boer, J, and Williams, O

Subjects
*ADENOSINE triphosphatase, *ACUTE myeloid leukemia, *PROGENITOR cells, *TRANSCRIPTION factors, *GENE expression, *GENE silencing, *TELOMERASE
Abstract

The most frequent chromosomal translocations in pediatric acute myeloid leukemia affect the 11q23 locus and give rise to mixed lineage leukemia (MLL) fusion genes, MLL-AF9 being the most prevalent. The MLL-AF9 fusion gene has been shown to induce leukemia in both mouse and human models. In this study, we demonstrate that leukemogenic activity of MLL-AF9 requires RUVBL2 (RuvB-like 2), an AAA+ ATPase family member that functions in a wide range of cellular processes, including chromatin remodeling and transcriptional regulation. Expression of RUVBL2 was dependent on MLL-AF9, as it increased upon immortalization of human cord blood-derived hematopoietic progenitor cells with the fusion gene and decreased following loss of fusion gene expression in conditionally immortalized mouse cells. Short hairpin RNA-mediated silencing experiments demonstrated that both the immortalized human cells and the MLL-AF9-expressing human leukemia cell line THP-1 required RUVBL2 expression for proliferation and survival. Furthermore, inhibition of RUVBL2 expression in THP-1 cells led to reduced telomerase activity and clonogenic potential. These data were confirmed with a dominant-negative Walker B-mutated RUVBL2 construct. Taken together, these data suggest the possibility of targeting RUVBL2 as a potential therapeutic strategy for MLL-AF9-associated leukemia. [ABSTRACT FROM AUTHOR]

Published
2013
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