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46 results on '"Park, Eunsil"'

1. Mpox Neutralizing Antibody Response to LC16m8 Vaccine in Healthy Adults

Author

Morino, Eriko, primary, Mine, Sohtaro, additional, Tomita, Noriko, additional, Uemura, Yukari, additional, Shimizu, Yosuke, additional, Saito, Sho, additional, Suzuki, Tetsuya, additional, Okumura, Nobumasa, additional, Iwasaki, Haruka, additional, Terada, Junko, additional, Ainai, Akira, additional, Sakai, Yusuke, additional, Park, Eunsil, additional, Seki, Sayuri, additional, Akazawa, Daisuke, additional, Shimojima, Masayuki, additional, Shiwa-Sudo, Nozomi, additional, Virhuez-Mendoza, Milagros, additional, Miyauchi, Kosuke, additional, Moriyama, Saya, additional, Iwata-Yoshikawa, Naoko, additional, Harada, Michiko, additional, Harada, Shigeyoshi, additional, Hishiki, Takayuki, additional, Kotaki, Ryutaro, additional, Matsumura, Takayuki, additional, Miyamoto, Sho, additional, Kanno, Takayuki, additional, Isogawa, Masanori, additional, Watashi, Koichi, additional, Nagata, Noriyo, additional, Ebihara, Hideki, additional, Takahashi, Yoshimasa, additional, Maeda, Ken, additional, Matano, Tetsuro, additional, Wakita, Takaji, additional, Suzuki, Tadaki, additional, Sugiura, Wataru, additional, Ohmagari, Norio, additional, and Ujiie, Mugen, additional

Published
2024
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2. High Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Infection among the Dog Population in Thailand

Author

Ishijima, Keita, primary, Phichitraslip, Thanmaporn, additional, Naimon, Nattakarn, additional, Ploypichai, Preeyaporn, additional, Kriebkajon, Benyapa, additional, Chinarak, Torntun, additional, Sridaphan, Jirasin, additional, Kritiyakan, Anamika, additional, Prasertsincharoen, Noppadol, additional, Jittapalapong, Sathaporn, additional, Tangcham, Kanate, additional, Rerkamnuaychoke, Worawut, additional, Kuroda, Yudai, additional, Taira, Masakatsu, additional, Tatemoto, Kango, additional, Park, Eunsil, additional, Virhuez-Mendoza, Milagros, additional, Inoue, Yusuke, additional, Harada, Michiko, additional, Yamamoto, Tsukasa, additional, Nishino, Ayano, additional, Matsuu, Aya, additional, and Maeda, Ken, additional

Published
2023
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3. A novel nairovirus associated with acute febrile illness in Hokkaido, Japan

Author

Kodama, Fumihiro, Yamaguchi, Hiroki, Park, Eunsil, Tatemoto, Kango, Sashika, Mariko, Nakao, Ryo, Terauchi, Yurino, Mizuma, Keita, Orba, Yasuko, Kariwa, Hiroaki, Hagiwara, Katsuro, Okazaki, Katsunori, Goto, Akiko, Komagome, Rika, Miyoshi, Masahiro, Ito, Takuya, Yamano, Kimiaki, Yoshii, Kentaro, Funaki, Chiaki, Ishizuka, Mariko, Shigeno, Asako, Itakura, Yukari, Bell-Sakyi, Lesley, Edagawa, Shunji, Nagasaka, Atsushi, Sakoda, Yoshihiro, Sawa, Hirofumi, Maeda, Ken, Saijo, Masayuki, and Matsuno, Keita

Published
2021
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4. Simple and rapid detection of severe fever with thrombocytopenia syndrome virus in cats by reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay using a dried reagent

Author

ISHIJIMA, Keita, primary, YOKONO, Kota, additional, PARK, Eunsil, additional, TAIRA, Masakatsu, additional, TATEMOTO, Kango, additional, KURODA, Yudai, additional, MENDOZA, Milagros Virhuez, additional, INOUE, Yusuke, additional, HARADA, Michiko, additional, MATSUU, Aya, additional, MORIKAWA, Shigeru, additional, FUKUSHI, Shuetsu, additional, and MAEDA, Ken, additional

Published
2023
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6. Lethal Disease in Dogs Naturally Infected with Severe Fever with Thrombocytopenia Syndrome Virus

Author

Ishijima, Keita, primary, Tatemoto, Kango, additional, Park, Eunsil, additional, Kimura, Masanobu, additional, Fujita, Osamu, additional, Taira, Masakatsu, additional, Kuroda, Yudai, additional, Mendoza, Milagros Virhuez, additional, Inoue, Yusuke, additional, Harada, Michiko, additional, Matsuu, Aya, additional, Shimoda, Hiroshi, additional, Kuwata, Ryusei, additional, Morikawa, Shigeru, additional, and Maeda, Ken, additional

Published
2022
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8. Seroprevalence of antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in household dogs in Japan

Author

Yudai Kuroda, Park Eunsil, Genta Ito, Ken Maeda, Yuko Goto-Koshino, Takehisa Soma, and Yasuyuki Momoi

Subjects
Veterinary medicine, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Enzyme-Linked Immunosorbent Assay, Antibodies, Viral, medicine.disease_cause, coronavirus disease 2019, Dogs, Japan, Seroepidemiologic Studies, antibody, Internal Medicine, medicine, Animals, Seroprevalence, Dog Diseases, Respiratory system, Target antigen, Coronavirus, General Veterinary, biology, SARS-CoV-2, business.industry, COVID-19, Spike Protein, Note, Spike Glycoprotein, Coronavirus, dog, biology.protein, Antibody, business, severe acute respiratory syndrome coronavirus 2
Abstract

We investigated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among dogs in the Tokyo area via enzyme-linked immunosorbent assay (ELISA) using the spike protein as the target antigen. Plasma samples from 494 household dogs and blood-donor dogs were tested from July 2020 to January 2021. Of these samples, three showed optical densities that were higher than the mean plus two standard deviations of the mean of the negative-control optical densities (ODs). Of these three samples, only the sample with the highest OD by ELISA was confirmed positive by virus neutralization testing. The positive dog presented no SARS-CoV-2-related symptoms. The positivity rate of SARS-CoV-2 infections among dogs in the Tokyo area was approximately 0.2%.

Published
2021

12. Prevalence of Antibodies to Crimean-Congo Hemorrhagic Fever Virus in Ruminants, Nigeria, 2015

Author

A I Adebiyi, Daniel Oladimeji Oluwayelu, Tomoki Yoshikawa, Masayuki Saijo, Oyewale Tomori, Anitha Varghese, Park Eunsil, Shuetsu Fukushi, Roger Hewson, Shigeru Morikawa, Babak Afrough, and E.J. Neumann

Subjects
Microbiology (medical), Crimean–Congo hemorrhagic fever, Epidemiology, 030231 tropical medicine, prevalence, lcsh:Medicine, Nigeria, Human pathogen, Prevalence of Antibodies to Crimean-Congo Hemorrhagic Fever Virus in Ruminants, Nigeria, 2015, Antibodies, Viral, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, CCHF, antibodies Crimean-Congo hemorrhagic fever virus, Medicine, antibodies, Animals, lcsh:RC109-216, viruses, 030212 general & internal medicine, biology, business.industry, lcsh:R, Dispatch, Ruminants, Hemorrhagic fever virus, medicine.disease, Virology, Crimean-Congo hemorrhagic fever virus, zoonoses, Infectious Diseases, CCHFV, Hemorrhagic Fever Virus, Crimean-Congo, biology.protein, Crimean-Congo hemorrhagic fever, Cattle, Hemorrhagic Fever, Crimean, Antibody, business, Crimean Congo hemorrhagic fever virus
Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly transmissible human pathogen. Infection is often misdiagnosed, in part because of poor availability of data in disease-endemic areas. We sampled 150 apparently healthy ruminants throughout Nigeria for virus seropositivity and detected virus-specific IgG in cattle (24%) and goats (2%), highlighting the need for further investigations.

Published
2020

16. Reduced Resistance of SARS-CoV-2 Variants Toward Affinity-Matured Serological Immunity

Author

Kazu Okuma, Ken Maeda, Shuetsu Fukushi, Tsuguto Fujimoto, Takashi Sato, Keita Ishijima, Tadaki Suzuki, Hitomi Kinoshita, Makoto Ohnishi, Souichi Yamada, Kiyoko Nojima, Takayuki Kanno, Masanori Isogawa, Masaharu Shinkai, Minoru Tobiume, Ayae Nishiyama, Keisuke Tonouchi, Natsuo Tachikawa, Taishi Onodera, Ai Kawana-Tachikawa, Lin Sun, Kazutaka Terahara, Takayuki Matsumura, Tomohiro Takano, Saya Moriayma, Shigeki Nakamura, Takahiro Okai, Tetsuro Matano, Park Eunsil, Yudai Kuroda, Yoshimasa Takahashi, Takaji Wakita, and Yu Adachi

Subjects
biology, business.industry, Virology, Virus, Neutralization, Antigenic drift, Serology, Affinity maturation, biology.protein, Potency, Medicine, Antibody, Neutralizing antibody, business
Abstract

SARS-CoV-2 variants have raised concerns regarding resistance to neutralizing antibodies elicited by the parental virus. In the present study, we monitored multiple parameters of neutralizing antibodies in convalescent plasma up to 10 months after the symptom onset. In contrast to marked decline of neutralizing antibody titers, the neutralization potency per antibody increased with time. The antigenic drift of B.1.351 (501Y.V2) and P.1 (501Y.V3) variants conferred resistance to neutralization by convalescent plasma in the early phase; however, the resistance of these variants was attenuated by progressive increase of neutralization potency and breadth over time. Furthermore, this increase in the neutralization potency/breadth were highly correlated with the affinity maturation of IgG antibodies that target virus conserved sites with extended half-lives. Despite a quantitative decline in the neutralizing antibody titers, the serological immunity shapes the neutralization potency and breadth with time, thereby acquiring persistent neutralizing activity toward SARS-CoV-2 variants. Declaration of Interest: All authors declare that they have no competing interests. Ethical Approval: All studies were approved by the Institutional Review Board of the National Institute of Infectious Diseases (#1127, #1132, and #1197). This study was performed in accordance with the Declaration of Helsinki. All volunteers provided written informed consent prior to enrollment.

Published
2021

17. Neutralizing Antibody-Independent SARS-CoV-2 Control Correlated with Intranasal Vaccine-Induced CD8 + T-Cell Responses

Author

Kohji Kusano, Noriyo Nagata, Naoko Iwata-Yoshikawa, Ken Maeda, Midori Nakamura-Hoshi, Tetsuro Matano, Trang Thi Thu Hau, Ryutaro Shimazaki, Midori Okazaki, Hiroyuki Yamamoto, Hiroshi Ishii, Ai Kawana-Tachikawa, Takushi Nomura, Nozomi Shiwa, Yuriko Suzaki, Sachie Daigen, Shigeyoshi Harada, Tadaki Suzuki, Taishi Onodera, Sayuri Seki, Yoshimasa Takahashi, Yasushi Ami, Masako Nishizawa, and Park Eunsil

Subjects
History, Polymers and Plastics, biology, business.industry, Virology, Industrial and Manufacturing Engineering, Viral vector, Vaccination, Antigen, Pandemic, biology.protein, Cytotoxic T cell, Medicine, Business and International Management, Antibody, business, Neutralizing antibody, Viral load
Abstract

Effective vaccines are essential for the control of the COVID-19 pandemic. Currently-developed vaccines inducing SARS-CoV-2 spike (S) antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants. Here, we investigated the efficacy of an intranasal vaccine expressing viral non-S antigens against intranasal SARS-CoV-2 challenge in cynomolgus macaques. Nine vaccinated macaques exhibited significantly reduced viral load in nasopharyngeal swabs on day 2 post-challenge compared to nine unvaccinated controls. The viral control in the absence of SARS-CoV-2-specific NAbs was significantly correlated with vaccine-induced viral antigen-specific CD8+ T-cell responses. Our results indicate that CD8+ T-cell induction by intranasal vaccination can result in NAb-independent control of SARS-CoV-2 infection, highlighting a potential of vaccine-induced CD8+ T-cell responses to contribute to COVID-19 containment. Funding: This work was supported by Japan Agency for Medical Research and Development (AMED [JP19fk0108104 to A.K.-T. and JP20nk0101601, JP20jm0110012, JP21fk0410035, JP21fk0108125, and JP21jk0210002 to T.M.]) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan (JSPS Grants-in-Aid for Scientific Research [21H02745 to T.M.]). Declaration of Interests: H.I., K.K., R.S., and T.M are the inventors on Patent Cooperation Treaty (PCT) application for SeV-NME vaccine. Authors have no other conflicts of interest to declare. Ethics Approval Statement: Approval by the Committee on the Ethics of Animal Experiments in NIID (permission number: 520001) under the guidelines for animal experiments in accordance with the Guidelines for Proper Conduct of Animal Experiments established by the Science Council of Japan.

Published
2021

22. A novel nairovirus associated with acute febrile illness in Hokkaido, Japan

Author

Fumihiro Kodama, Hiroki Yamaguchi, Park, Eunsil, Kango Tatemoto, Mariko Sashika, Ryo Nakao, Yurino Terauchi, Keita Mizuma, Yasuko Orba, Hiroaki Kariwa, Katsuro Hagiwara, Katsunori Okazaki, Akiko Goto, Rika Komagome, Masahiro Miyoshi, Takuya Ito, Kimiaki Yamano, Kentaro Yoshii, Chiaki Funaki, and Mariko Ishizuka

Abstract

The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014–2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Impact of Rotavirus Vaccine Introduction on Rotavirus-Associated Seizures and a Related Possible Mechanism.

Author

Yeom, Jung Sook, Kim, Young-Soo, Kim, Rock Bum, Park, Ji Sook, Seo, Ji-Hyun, Park, Eunsil, Lim, Jae-Young, Park, Chan-Hoo, Woo, Hyang-Ok, and Youn, Hee-Shang

Subjects
ROTAVIRUSES, SEIZURES (Medicine), ROTAVIRUS vaccines, GASTROENTERITIS, GASTROINTESTINAL diseases
Abstract

To determine whether clinical features of rotavirus-associated seizures have been altered by rotavirus vaccination, we compared clinical and laboratory data of 2 groups of patients with rotavirus-associated seizures: pre– and post–vaccine introduction groups. The seizure characteristics differed significantly between the groups, with a lower incidence of fever at seizure onset, longer interval between the onset of gastroenteritis and seizures, and more frequent seizures in the postintroduction group. These characteristics may suggest that seizure susceptibility was increased in the postintroduction group. Based on the lower serum Cl– (102.1 ± 4.1 vs 98.2 ± 3.2 mg/dL; P < .01) and Ca2+ levels (9.2 ± 0.4 vs 9.0 ± 0.3 mg/dL; P = .12) in the postintroduction group, we propose that a change in the subjects’ susceptibility to the rotavirus enterotoxin may have played a role in increasing the seizure susceptibility in this group. Our results suggest that a rotavirus vaccination program may modulate the manifestations of rotavirus-associated seizures. [ABSTRACT FROM PUBLISHER]

Published
2015
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44. A Novel DNA Methyltransferase Inhibitor Is Effective in an In VivoModel of Myelodysplastic Syndrome

Author

Khawaja, Ghanwa, Chung, Yang Jo, Park, Eunsil, Difilippantonio, Micheal, Doroshow, James H., and Aplan, Peter D.

Abstract

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplasia and a propensity for transformation to acute myeloid leukemia (AML). MDS is frequently associated with epigenetic gene silencing via methylation of cytosine residues in gene regulatory regions, and DNA methyl-transferase 1 (DNMT1) inhibitors, such as 5'azacytidine and 5-aza-2'-deoxycytidine (decitabine, DAC), are two of the three agents that are FDA approved for treatment of MDS. Although these drugs are not curative, they induce hematological improvement or improved survival in a significant fraction of MDS patients. Two novel, thiol-substituted 2'-deoxycytidine (dCyd) analogs designated T-dCyd (4'-thio-2'-deoxycytidine) and Aza-T-dCyd (5-aza-4'-thio-2'-deoxycytidine) were synthesized and shown to be potent DNMT1 inhibitors in vitro. We evaluated these drugs in vivo using the NUP98-HOXD13 (NHD13) mouse model for MDS.

Published
2018
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45. The Runt Related Transcription Factor 2 (RUNX2) Regulates the Expression of Runx1in Luteinizing Granulosa Cells and Expanding Cumulus-Oocyte-Complexes (COCs).

Author

Park, Eunsil and Jo, Misung

Abstract

In response to the LH/FSH surge, a preovulatory follicle undergoes dramatic changes that culminate in ovulation and luteal formation. These changes are caused by actions of specific transcription factors that control periovulatory gene expression. Our previous studies showed that Runx1and Runx2expression were induced by the LH surge in periovulatory ovaries. Runx1expression was transient in periovulatory follicles and declined rapidly before ovulation, whereas Runx2expression was increased in periovulatory follicles and newly forming CL. Runx1and Runx2were also highly expressed in periovulatory COCs. In an attempt to identify the downstream targets of RUNX2, we performed microarray analyses using Runx2silenced granulosa cells. Interestingly, the microarray data revealed increased levels of Runx1mRNA in Runx2siRNA-treated cells. Further analyses of the Runx1gene revealed 2 consensus RUNX binding sites in the Runx1promoter region. Taken together with the inverse pattern of expression between Runx2and Runx1during the late periovulatory period, we hypothesized that RUNX2 plays a role in down-regulation of Runx1expression in luteinizing granulosa cells and/or expanding cumulus cells. To test this hypothesis, preovulatory granulosa cells or COCs were collected from eCG-primed immature rat ovaries and cultured with various reagents. First, to confirm the microarray data, granulosa cells were transfected with negative siRNA or Runx2siRNA and stimulated with agonists (forskolin + PMA) for 24 or 48 hr to induce Runx2expression. Real-time PCR and Western blot analyses confirmed the knockdown of Runx2expression and increases in Runx1expression in Runx2siRNA-treated cells. In addition, the levels of mRNA and protein for Ptgs2and Tnfaip6were also increased in Runx2silenced cells. Second, to assess whether Runx2over-expression can inhibitRunx1expression, granulosa cells were infected with adenovirus expressing Runx2(Ad-RUNX2). We found that Runx2over-expression reduced the agonist-stimulated Runx1, Ptgs2, and Tnfaip6expression. Next, to determine whether RUNX2 regulates Runx1expression at the transcriptional level, Runx1promoter constructs were generated and transfected into granulosa cells. Luciferase reporter assays revealed that mutation of RUNX binding sites in the Runx1promoter resulted in further induction of agonist-stimulated promoter activity of the Runx1gene. Lastly, to determine whether RUNX2 regulates Runx1expression in cumulus cells, COCs were stimulated with forskolin + amphiregulin to induce expansion. These agonists induced full expansion of COCs and increased the expression of COC expansion-related genes (Ptgs2, Tnfaip6, Has2, Ptx3and Cspg2) as well as Runx1. When COCs were infected with Ad-RUNX2, the agonist-stimulated expression of Runx1, Ptgs2, Tnfaip6, Has2,and Cspg2, but not Ptx3, was decreased compared to that in control COCs. Moreover, the over-expression of RUNX2 reduced COC expansion. Taken together, these data demonstrated that RUNX2 regulates the expression of Runx1, Ptgs2, Tnfaip6, Has2,and Cspg2in luteinizing granulosa cells and/or expanding cumulus cells. This novel finding suggests that RUNX2 contributes to the down-regulation of Runx1and several COC expansion genes during the periovulatory period to support proper COC expansion and luteinization. (supported by P20 RR15592, R01HD061617 and R03HD066012.)(poster)

Published
2011
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46. Activation of Hepatocyte Growth Factor/MET Signaling as a Mechanism of Acquired Resistance to a Novel YAP1/TEAD Small Molecule Inhibitor.

Author

Moure CJ, Vara B, Cheng MM, Sondey C, Muise E, Park E, Vela Ramirez JE, Su D, D'Souza S, Yan Q, Yeung CS, Zhang M, Mansueto MS, Linn D, Buchanan M, Foti R, DiMauro E, Long B, Simov V, and Barry ER

Subjects
Humans, Animals, Mice, Cell Line, Tumor, Xenograft Model Antitumor Assays, Small Molecule Libraries pharmacology, TEA Domain Transcription Factors, Cell Proliferation drug effects, Hepatocyte Growth Factor metabolism, Transcription Factors metabolism, Transcription Factors antagonists & inhibitors, Proto-Oncogene Proteins c-met antagonists & inhibitors, Proto-Oncogene Proteins c-met metabolism, Signal Transduction drug effects, Adaptor Proteins, Signal Transducing metabolism, Adaptor Proteins, Signal Transducing antagonists & inhibitors, YAP-Signaling Proteins, Drug Resistance, Neoplasm drug effects
Abstract

Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of cases are considered YAP1/TEAD dependent. Identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs, which may be necessary for YAP1 protein interactions, has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TEAD complex formation and transcriptional activity. We report the discovery and characterization of a novel YAP1/TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TEAD activity. In vivo, MRK-A showed a favorable tolerability profile in mice and demonstrated pharmacokinetics suitable for twice daily oral dosing in preclinical efficacy studies. Importantly, monotherapeutic targeting of YAP1/TEAD in preclinical models generated regressions in a mesothelioma CDX model; however, rapid resistance to therapy was observed. RNA-sequencing of resistant tumors revealed mRNA expression changes correlated with the resistance state and a marked increase of hepatocyte growth factor (HGF) expression. In vitro, exogenous HGF was able to fully rescue cytostasis induced by MRK-A in mesothelioma cell lines. In addition, co-administration of small molecule inhibitors of the MET receptor tyrosine kinase suppressed the resistance generating effect of HGF on MRK-A induced growth inhibition. In this work, we report the structure and characterization of MRK-A, demonstrating potent and specific inhibition of YAP1/TAZ-TEAD-mediated transcriptional responses, with potential implications for treating malignancies driven by altered Hippo signaling, including factors resulting in acquired drug resistance., (©2024 American Association for Cancer Research.)

Published
2024
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