323 results on '"Eun-Sil Park"'
Search Results
2. The comparison of pathogenicity among SARS-CoV-2 variants in domestic cats
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Eun-sil Park, Yudai Kuroda, Akihiko Uda, Yoshihiro Kaku, Akiko Okutani, Akitoyo Hotta, Kango Tatemoto, Keita Ishijima, Yusuke Inoue, Michiko Harada, Yasushi Ami, Masayuki Shirakura, Shinji Watanabe, Yasushi Suzuki, Toshihiko Harada, Akira Ainai, Nozomi Shiwa, Yusuke Sakai, Naoko Iwata-Yoshikawa, Noriyo Nagata, Tadaki Suzuki, Hideki Hasegawa, and Ken Maeda
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Medicine ,Science - Abstract
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected or isolated from domestic cats. It is unclear whether cats play an important role in the SARS-CoV-2 transmission cycle. In this study, we examined the susceptibility of cats to SARS-CoV-2, including wild type and variants, by animal experiments. Cats inoculated with wild type, gamma, and delta variants secreted a large amount of SARS-CoV-2 for 1 week after the inoculation from nasal, oropharyngeal, and rectal routes. Only 100 TCID50 of virus could infect cats and replicate well without severe clinical symptoms. In addition, one cat inoculated with wild type showed persistent virus secretion in feces for over 28 days post-inoculation (dpi). The titer of virus-neutralizing (VN) antibodies against SARS-CoV-2 increased from 11 dpi, reaching a peak at 14 dpi. However, the omicron variant could not replicate well in cat tissues and induced a lower titer of VN antibodies. It is concluded that cats were highly susceptible to SARS-CoV-2 infection, but not to the Omicron Variant, which caused the attenuated pathogenicity.
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- 2024
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3. Construction of Vero cell-adapted rabies vaccine strain by five amino acid substitutions in HEP-Flury strain
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Michiko Harada, Aya Matsuu, Eun-Sil Park, Yusuke Inoue, Akihiko Uda, Yoshihiro Kaku, Akiko Okutani, Guillermo Posadas-Herrera, Keita Ishijima, Satoshi Inoue, and Ken Maeda
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Medicine ,Science - Abstract
Abstract Rabies virus (RABV) causes fatal neurological disease. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) using inactivated-virus vaccines are the most effective measures to prevent rabies. In Japan, HEP-Flury, the viral strain, used as a human rabies vaccine, has historically been propagated in primary fibroblast cells derived from chicken embryos. In the present study, to reduce the cost and labor of vaccine production, we sought to adapt the original HEP-Flury (HEP) to Vero cells. HEP was repeatedly passaged in Vero cells to generate ten- (HEP-10V) and thirty-passaged (HEP-30V) strains. Both HEP-10V and HEP-30V grew significantly better than HEP in Vero cells, with virulence and antigenicity similar to HEP. Comparison of the complete genomes with HEP revealed three non-synonymous mutations in HEP-10V and four additional non-synonymous mutations in HEP-30V. Comparison among 18 recombinant HEP strains constructed by reverse genetics and vesicular stomatitis viruses pseudotyped with RABV glycoproteins indicated that the substitution P(L115H) in the phosphoprotein and G(S15R) in the glycoprotein improved viral propagation in HEP-10V, while in HEP-30V, G(V164E), G(L183P), and G(A286V) in the glycoprotein enhanced entry into Vero cells. The obtained recombinant RABV strain, rHEP-PG4 strain, with these five substitutions, is a strong candidate for production of human rabies vaccine.
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- 2024
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4. Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats
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Yusuke Sakai, Serina Mura, Yuko Kuwabara, Saya Kagimoto, Masashi Sakurai, Masahiro Morimoto, Eun-sil Park, Masayuki Shimojima, Noriyo Nagata, Yasushi Ami, Tomoki Yoshikawa, Naoko Iwata-Yoshikawa, Shuetsu Fukushi, Shumpei Watanabe, Takeshi Kurosu, Akiko Okutani, Masanobu Kimura, Koichi Imaoka, Masayuki Saijo, Shigeru Morikawa, Tadaki Suzuki, and Ken Maeda
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severe fever with thrombocytopenia syndrome ,cats ,histopathology ,lymph nodes ,germinal centre reaction ,Microbiology ,QR1-502 - Abstract
IntroductionSevere fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS.MethodsLymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed.ResultsIn the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production.DiscussionThese results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses.
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- 2024
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5. Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents
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Takayuki Hishiki, Takeshi Morita, Daisuke Akazawa, Hirofumi Ohashi, Eun-Sil Park, Michiyo Kataoka, Junki Mifune, Kaho Shionoya, Kana Tsuchimoto, Shinjiro Ojima, Aa Haeruman Azam, Shogo Nakajima, Madoka Kawahara, Tomoki Yoshikawa, Masayuki Shimojima, Kotaro Kiga, Ken Maeda, Tadaki Suzuki, Hideki Ebihara, Yoshimasa Takahashi, and Koichi Watashi
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monkeypox ,mpox ,antiviral ,mycophenolic acid ,IMP dehydrogenase ,gemcitabine ,Microbiology ,QR1-502 - Abstract
ABSTRACT Mpox virus (formerly monkeypox virus [MPXV]) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation. These compounds showed broad-spectrum anti-orthopoxvirus activities and presented lower 90% inhibitory concentrations (0.026 to 0.89 μM) than brincidofovir, an approved anti-smallpox agent. These three compounds have been suggested to target the postentry step to reduce the intracellular production of virions. Knockdown of IMP dehydrogenase (IMPDH), the rate-limiting enzyme of guanosine biosynthesis and a target of MPA, dramatically reduced MPXV DNA production. Moreover, supplementation with guanosine recovered the anti-MPXV effect of MPA, suggesting that IMPDH and its guanosine biosynthetic pathway regulate MPXV replication. By targeting IMPDH, we identified a series of compounds with stronger anti-MPXV activity than MPA. This evidence shows that IMPDH is a potential target for the development of anti-MPXV agents. IMPORTANCE Mpox is a zoonotic disease caused by infection with the mpox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against mpox in the United States. Although brincidofovir and tecovirimat are drugs approved for the treatment of smallpox by the U.S. Food and Drug Administration, their efficacy against mpox has not been established. Moreover, these drugs may present negative side effects. Therefore, new anti-mpox virus agents are needed. This study revealed that gemcitabine, trifluridine, and mycophenolic acid inhibited mpox virus propagation and exhibited broad-spectrum anti-orthopoxvirus activities. We also suggested IMP dehydrogenase as a potential target for the development of anti-mpox virus agents. By targeting this molecule, we identified a series of compounds with stronger anti-mpox virus activity than mycophenolic acid.
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- 2023
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6. Distinct niche structures and intrinsic programs of fallopian tube and ovarian surface epithelial cells
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Guyu Qin, Eun-Sil Park, Xueqing Chen, Sen Han, Dongxi Xiang, Fang Ren, Gang Liu, Huidong Chen, Guo-Cheng Yuan, and Zhe Li
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Biological sciences ,Molecular biology ,Cell biology ,Transcriptomics ,Science - Abstract
Summary: Epithelial ovarian cancer (EOC) can originate from either fallopian tube epithelial (FTE) or ovarian surface epithelial (OSE) cells, but with different latencies and disease outcomes. To address the basis of these differences, we performed single cell RNA-sequencing of mouse cells isolated from the distal half of fallopian tube (FT) and surface layer of ovary. We find at the molecular level, FTE secretory stem/progenitor cells and OSE cells resemble mammary luminal progenitors and basal cells, respectively. An FT stromal subpopulation, enriched with Pdgfra+ and Esr1+ cells, expresses multiple secreted factor (e.g., IGF1) and Hedgehog pathway genes and may serve as a niche for FTE cells. In contrast, Lgr5+ OSE cells express similar genes largely by themselves, raising a possibility that they serve as their own niche. The differences in intrinsic expression programs and niche organizations of FTE and OSE cells may contribute to their different courses toward the development of EOCs.
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- 2023
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7. Pet Animals Were Infected with SARS-CoV-2 from Their Owners Who Developed COVID-19: Case Series Study
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Yudai Kuroda, Kei Watanabe, Tsukasa Yamamoto, Hiroki Suzuki, Eun-sil Park, Keita Ishijima, Kango Tatemoto, Milagros Virhuez-Mendoza, Yusuke Inoue, Michiko Harada, Ayano Nishino, Tsuyoshi Sekizuka, Makoto Kuroda, Tsuguto Fujimoto, Genki Ishihara, Ryo Horie, Kosuke Kawamoto, and Ken Maeda
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SARS-CoV-2 ,cats ,dogs ,Microbiology ,QR1-502 - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pets owned by coronavirus disease 2019 (COVID-19) patients has been reported around the world. However, how often the animals are exposed to SARS-CoV-2 by their owners is still unclear. We have collected swab samples from COVID-19 patients’ pets and performed real-time RT-PCR to detect the viral genome. In total, 8 of 53 dogs (15.1%) and 5 of 34 cats (14.7%) tested positive for the SARS-CoV-2 N gene. The result of a virus neutralization (VN) test also showed VN antibodies in four cats and six dogs. Our results indicate that the virus often passed from infected owners to their pets, which then excreted the virus despite having no or mild clinical signs.
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- 2023
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8. A retrospective survey of the seroprevalence of severe fever with thrombocytopenia syndrome virus in wild animals in Japan
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Ayaka Okada, Akitoyo Hotta, Masanobu Kimura, Eun‐sil Park, Shigeru Morikawa, and Yasuo Inoshima
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seroprevalence ,severe fever with thrombocytopenia syndrome ,wild animal ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Severe fever with thrombocytopenia syndrome (SFTS) has a high fatality rate and is caused by SFTS virus (SFTSV). Currently, SFTS is endemic to some areas in western Japan, and wild animals are considered to play important roles in the circulation of SFTSV in the environment. Previous retrospective surveys using samples mainly obtained between 2006 and 2015 revealed serological evidence of SFTSV infection in wild animals; however, seroprevalence before 2006 remains unclear. In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas.
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- 2021
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9. Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques.
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Takushi Nomura, Hiroyuki Yamamoto, Masako Nishizawa, Trang Thi Thu Hau, Shigeyoshi Harada, Hiroshi Ishii, Sayuri Seki, Midori Nakamura-Hoshi, Midori Okazaki, Sachie Daigen, Ai Kawana-Tachikawa, Noriyo Nagata, Naoko Iwata-Yoshikawa, Nozomi Shiwa, Shun Iida, Harutaka Katano, Tadaki Suzuki, Eun-Sil Park, Ken Maeda, Yuriko Suzaki, Yasushi Ami, and Tetsuro Matano
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10-17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.
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- 2021
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10. Diagnostic system for the detection of severe fever with thrombocytopenia syndrome virus RNA from suspected infected animals.
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Eun-Sil Park, Osamu Fujita, Masanobu Kimura, Akitoyo Hotta, Koichi Imaoka, Masayuki Shimojima, Masayuki Saijo, Ken Maeda, and Shigeru Morikawa
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Medicine ,Science - Abstract
BackgroundSevere fever with thrombocytopenia syndrome virus (SFTSV) causes severe hemorrhagic fever in humans and cats. Clinical symptoms of SFTS-infected cats resemble those of SFTS patients, whereas SFTS-contracted cats have high levels of viral RNA loads in the serum and body fluids. Due to the risk of direct infection from SFTS-infected cats to human, it is important to diagnose SFTS-suspected animals. In this study, a reverse transcription polymerase chain reaction (RT-PCR) was newly developed to diagnose SFTS-suspected animals without non-specific reactions.Methodology/principle findingsFour primer sets were newly designed from consensus sequences constructed from 108 strains of SFTSV. A RT-PCR with these four primer sets successfully and specifically detected four clades of SFTSV. Their limits of detection are 1-10 copies/reaction. Using this RT-PCR, 5 cat cases among 56 SFTS-suspected animal cases were diagnosed as SFTS. From these cats, IgM or IgG against SFTSV were detected by enzyme-linked immunosorbent assay (ELISA), but not neutralizing antibodies by plaque reduction neutralization titer (PRNT) test. This phenomenon is similar to those of fatal SFTS patients.Conclusion/significanceThis newly developed RT-PCR could detect SFTSV RNA of several clades and from SFTS-suspected animals. In addition to ELISA and PRNT test, the useful laboratory diagnosis systems of SFTS-suspected animals has been made in this study.
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- 2021
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11. Long-term organoid culture reveals enrichment of organoid-forming epithelial cells in the fimbrial portion of mouse fallopian tube
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Ying Xie, Eun-Sil Park, Dongxi Xiang, and Zhe Li
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Biology (General) ,QH301-705.5 - Abstract
A recent paradigm shift in ovarian cancer research is the finding that many ovarian cancers may originate from fallopian tube epithelial (FTE) cells. As tissue stem and progenitor cells often serve as cells of origin of cancer, a better understanding of FTE stem/progenitor cells and how they become transformed is essential for early detection and prevention of ovarian cancer. To facilitate study of FTE stem/progenitor cells in model systems, we established an organoid culture system for mouse FTE cells. We find that EPCAM+ mouse FTE cells can be stably cultured long-term under a minimal condition of activated EGF signaling and suppressed TGFbeta signaling. We show that both Notch and Wnt signaling are required for growth of FTE cells in organoids, and further activation of Wnt signaling supports their maturation toward the ciliated cell lineage. Lastly, by analyzing the frequency of organoid-forming cells in different portions of the fallopian tube (FT), we find that the distal portion of the FT, which includes the fimbria, is enriched with organoid-forming FTE stem cells. Keywords: Fallopian tube epithelial cell, Oviduct, Organoid culture, Tissue stem cell, Fimbria, Cellular origin of ovarian cancer
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- 2018
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12. Clinical features of Epstein-Barr Virus-associated Infectious Mononucleosis According to Age Group in Children
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Soram Lee, Ju-Young Chung, Jung Je Park, Ji-Hyun Seo, Jae Young Kim, Jung Sook Yeom, Eun-Sil Park, Jae-Young Lim, Hyang-Ok Woo, and Hee-Shang Youn
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epstein-barr virus infection ,infectious mononucleosis ,pediatrics ,Medicine (General) ,R5-920 - Abstract
ObjectivesFew studies of pediatric Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM) have been conducted in Korea. We evaluated the clinical features of children with IM to define differences according to age. MethodsWe conducted retrospective chart reviews of 68 children aged 0 to 15 years who were diagnosed by EBV-associated IM with EBV-Viral Capsid Antigen(VCA) IgM at laboratory test and were admitted between 2010 and 2014. The children were classified into four age groups: aged 0–3, 4–6, 7–9, and 10–15 years. ResultsThe age distribution of patients was as follows: 19 (27.9%) 0–3, 25 (36.8%) 4–6, 13 (19.1%) 7–9, and 11 (16.2%) 10–15. Fever was the most common presentation regardless of age. It was more common in the 0–3 group than the 4–6 group (P = 0.018). Pharyngitis was more common in the 7–9 group than the 0–3 group (P = 0.048), and myalgia was more common in the 10–15 group than the 0–3 group (P = 0.007). Pharyngitis was accompanied by lymphadenopathy, protracted fever, and rash. In the 0–3 age group, the prevalence of rash was higher while the percentage of atypical lymphocytes was lower, but there was no statistical support for this tendency. There were no differences in the frequency of hepatosplenomegaly or laboratory findings between age groups. ConclusionsIM is not uncommon in young children and its clinical presentation varies with age. Therefore, IM should be suspected in young febrile children with pharyngitis and rash despite low percentages of atypical lymphocytes.
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- 2018
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13. Pullulanase Is Necessary for the Efficient Intracellular Growth of Francisella tularensis.
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Akihiko Uda, Neekun Sharma, Kazuhiro Takimoto, Tian Deyu, Yuuki Koyama, Eun-Sil Park, Osamu Fujita, Akitoyo Hotta, and Shigeru Morikawa
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Medicine ,Science - Abstract
Pullulanase, an enzyme that catalyzes the hydrolysis of polysaccharides, has been identified in a broad range of organisms, including bacteria, yeasts, fungi, and animals. The pullulanase (pulB; FTT_0412c) of F. tularensis subspecies tularensis Schu S4 is considered to be a homologue of the type I pullulanase (pulA) of the other Francisella subspecies. The significance of Francisella pullulanase has been obscure until now. In the present study, we characterized a recombinant PulB of F. tularensis SCHU P9, which was expressed as a his-tagged protein in Escherichia coli. The recombinant PulB was confirmed to be a type I pullulanase by its enzymatic activity in vitro. A pulB gene knockout mutant of F. tularensis SCHU P9 (ΔpulB) was constructed using the TargeTron Knockout system and plasmid pKEK1140 to clarify the function of PulB during the growth of F. tularensis in macrophages. The intracellular growth of the ΔpulB mutant in murine macrophage J774.1 cells was significantly reduced compared with that of the parental strain SCHU P9. Expression of PulB in ΔpulB, using an expression plasmid, resulted in the complementation of the reduced growth in macrophages, suggesting that PulB is necessary for the efficient growth of F. tularensis in macrophages. To assess the role of PulB in virulence, the knockout and parent bacterial strains were used to infect C57BL/6J mice. Histopathological analyses showed that tissues from ΔpulB-infected mice showed milder lesions compared to those from SCHU P9-infected mice. However, all mice infected with SCHU P9 and ΔpulB showed the similar levels of bacterial loads in their tissues. The results suggest that PulB plays a significant role in bacterial growth within murine macrophage but does not contribute to bacterial virulence in vivo.
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- 2016
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14. Synthesis and Pesticidal Activities of 5-(2-Cyclopropylaminopyrimidin-4-yl)-4-(thiophenyl)thiazole Derivatives
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Won-Sik Choi, Seok-Woo Nam, Il-Doo Kim, Seung-Han Kim, Kun-Ho Park, In-Kyung Bae, Eun-Sil Park, Hwang-Ju Jeon, and Sung-Eun Lee
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Chemistry ,QD1-999 - Abstract
Pesticidal activities of 4-[5-(2-cyclopropylaminopyrimidin-4-yl)-4-(4-chloro-2-fluoro-phenyl)thiazol-2-yl]-1-methylpiperidine, designated as Comp I, have been determined against a mosquito larva, Culex pipiens pallens, and a phytopathogenic fungus, Phytophthora capsici. Comp I was used as the leading compound in this study. The compounds were synthesized by reacting them with two functional groups, 3-thiophenyl and 2-thiophenyl groups, instead of 4-chloro-2-fluorophenyl group in Comp I. Other functional groups such as 2-aminothiazole, 2-(1-methylpiperazin-4-yl)thiazole, and 2-(piperazin-4-yl)thiazole were also introduced instead of 2-methylpiperidin-4-yl-thiazole of Comp I. Compounds designated as XIII-6~XV-7 were newly synthesized and their structures were confirmed by 1H- and 13C-NMR spectroscopy. Mosquito larvicidal activities of all the synthesized compounds against C. pipiens pallens were examined and Comp I among them showed the strongest larvicidal activity as 0.513 mM of LC50 value. The fungicidal activities of all the synthesized compounds against P. capsici were examined using the whole plant method. Among the XIII-6~XV-7 chemicals, 5-(2-cyclopropylaminopyrimidin-4-yl)-4-(thiophen-2-yl)thiazol-2-amine (VIII-6) showed the most potent antifungal activity in vivo. While the EC50 value of the commercial fungicide dimethomorph was 4.26 μM, EC50 of VIII-6 was 0.94 μM. Therefore, thiazole derivatives can be considered as viable candidates for the control of mosquito larvae and plant diseases.
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- 2015
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15. Antifungal and Antiaflatoxigenic Methylenedioxy-Containing Compounds and Piperine-Like Synthetic Compounds
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Young-Sun Moon, Won-Sik Choi, Eun-Sil Park, In Kyung Bae, Sung-Deuk Choi, Ockjin Paek, Sheen-Hee Kim, Hyang Sook Chun, and Sung-Eun Lee
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aflatoxin ,Aspergillus flavus ,methylenedioxy compounds ,piperine ,reverse transcription-PCR ,Medicine - Abstract
Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure–activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 μg/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 μg/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes.
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- 2016
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16. Prevalence of Antibodies to Crimean-Congo Hemorrhagic Fever Virus in Ruminants, Nigeria, 2015
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Oluwayelu, Daniel, Afrough, Babak, Adebiyi, Adebowale, Varghese, Anitha, Eun-Sil, Park, Fukushi, Shuetsu, Yoshikawa, Tomoki, Saijo, Masayuki, Neumann, Eric, Morikawa, Shigeru, Hewson, Roger, and Tomori, Oyewale
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Hemorrhagic fevers ,Resveratrol ,Information management ,Infection ,Goats ,Beef cattle ,Immunoglobulin G ,Meat industry ,Cattle ,Viremia ,Diseases ,Antibodies ,Nature ,Tick-borne diseases ,Workers ,Information accessibility ,Health - Abstract
Crimean-Congo hemorrhagic fever (CCHF) is a fatal, zoonotic, tickborne viral infection endemic to Africa, the Middle East, Asia, and Europe. The CCHF virus (CCHFV) is primarily maintained in nature in [...]
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- 2020
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17. Relationship between Communication Competence, Empathy and Geriatric Nursing Practice of Nurses Caring for Elderly Cancer Patients at a General Hospital: Focusing on Veterans Hospital.
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Eun Sil Park and Jeong Hye Kim
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EMPATHY ,EVIDENCE-based nursing ,SELF-evaluation ,GERIATRIC nursing ,HOSPITAL nursing staff ,QUESTIONNAIRES ,CANCER patients ,DESCRIPTIVE statistics ,ONCOLOGY nursing ,COMMUNICATION ,CLINICAL competence ,NATIONAL competency-based educational tests ,DATA analysis software ,TUMORS ,VETERANS' hospitals - Abstract
Purpose: The purpose of this study was to identify the relationship between communication competence, empathy, and geriatric nursing practice of nurses caring for elderly cancer patients and to provide evidence supporting the practice of geriatric nursing. Methods: This study was conducted on 149 nurses who had more than six months of nursing experience caring for cancer patients aged 65 or older at veterans hospital, a general hospital in Seoul, Korea. Communication competence, empathy, and geriatric nursing practice were measured using a self-reported questionnaire. Collected data were analyzed using the SPSS/WIN 27.0 program. Results: The mean of communication competence was 3.77±0.46 out of 5, empathy was 3.96±0.42 out of 5, and geriatric nursing practice was 3.40±0.35 out of 4. The participants' geriatric nursing practice showed a significant positive correlation with communication competence (r=.39, p<.001), and empathy (r=.47, p<.001). Conclusion: To improve the geriatric nursing practice of nurses caring for elderly cancer patients, it would be necessary to develop an effective program and apply interventions to improve communication competence and empathy for elderly cancer patients. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Parenting stress and interactive engagement behaviors in children with developmental delay
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Jung Sook Yeom, Rock Bum Kim, Jae Young Cho, Ji Sook Park, Eun Sil Park, Ji-Hyun Seo, Jae-Young Lim, and Hyang-Ok Woo
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Pediatrics, Perinatology and Child Health ,Pediatrics - Abstract
Background: In clinical practice, the importance of interactive engagement behaviors is overlooked in children with developmental problems other than autism spectrum disorder (ASD). Parenting stress affects children’s development but lacks attention from clinicians.Purpose: This study aimed to identify the characteristics of interactive engagement behaviors and parenting stress among non-ASD children with developmental delays (DDs). We also analyzed whether engagement behaviors affect parenting stress.Methods: At Gyeongsang National University Hospital, between May 2021 and October 2021, we retrospectively enrolled 51 consecutive patients diagnosed with DDs in language or cognition (but not ASD) in the delayed group and 24 typically developing children in the control group. The Korean version of the Parenting Stress Index-4 and Child Interactive Behavior Test were used to assess the participants.Results: The median age of the delayed group was 31.0 months (interquartile range, 25.0–35.5 months); this group included 42 boys (82.4%). There were no intergroup differences in child age, child sex, parental age, parental educational background, mother’s employment status, or marital status. Higher parenting stress (PPP=0.440). Instead, DDs contributed to total parenting stress, which was mediated by children’s overall interactive engagement behaviors (β=57.30, P
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- 2023
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19. A Comparison of Group Perceptions Toward Young Children’s Problematic Behaviors: Focusing on Speech-Language Pathologist, Early Childhood Special Education Teachers and Child Care Teachers
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Mi-Ra Oh, Woo-Jin Lee, and Eun-Sil Park
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- 2023
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20. Research Trends of Neurodiversity Using Keyword Network Analysis: Focus on Autism Spectrum Disorder
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Da Ye Jeong, Eun Sil Park, Ara Ko, Ji Eun Min, and Seung Chul Kwak
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
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21. A Study of the Gesture Vocabulary Types of 8- to 35-Month-Old Toddlers
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Chae-Won Jang, Eun-Sil Park, and Woo-Jin Lee
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- 2022
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22. Neurodevelopmental Outcomes of Neonatal Rotavirus-Associated Leukoencephalopathy
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Jae Young Cho, Jung Sook Yeom, Young-Soo Kim, Dae-Seob Choi, Ji Sook Park, Eun Sil Park, Ji-Hyun Seo, Jae-Young Lim, Hyang-Ok Woo, and Chan-Hoo Park
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Rotavirus ,Leukoencephalopathies ,Cerebral Palsy ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Infant, Newborn ,Humans ,Infant ,Neurology (clinical) ,General Medicine ,Magnetic Resonance Imaging ,White Matter ,Rotavirus Infections - Abstract
Rotavirus infection has been reported to be associated with neonatal seizures with a diffuse and symmetrical diffusion restriction of periventricular white matter, namely, neonatal rotavirus-associated leukoencephalopathy. The extensive white matter injury seen in this cohort raises concerns about the long-term neurodevelopmental outcomes. In the present study, we prospectively assessed the neurodevelopmental outcomes of 13 patients with neonatal rotavirus-associated leukoencephalopathy at a median age of 26 months (range, 23–68 months). Neurodevelopmental outcomes were evaluated using a neurological examination, developmental evaluations, and magnetic resonance imaging (MRI) of the brain. Overall, 6 of the 13 patients (46%) had abnormal neurodevelopmental outcomes: 1 patient had mental retardation, visual–motor integration (VMI) dysfunction, cerebral palsy, and epilepsy; 1 patient had cerebral palsy and VMI dysfunction; remaining 4 patients had VMI dysfunction. Follow-up MRI in 12 of 13 patients showed an increased signal intensity on periventricular white matter in all patients. These findings suggested that neonatal rotavirus-associated leukoencephalopathy could not be assumed to be benign in long-term neurodevelopment, particularly in VMI function. Early intervention and long-term follow-up are necessary for these patients. Our findings raise caution for rotavirus infection in this vulnerable population for infants.
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- 2022
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23. Data from Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer
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Juan R. Cubillos-Ruiz, Anniina Färkkilä, Alan D. D'Andrea, David Pépin, Dmitriy Zamarin, E. Alfonso Romero-Sandoval, Kevin Holcomb, Franck J. Barrat, Minkyung Song, Andrew V. Kossenkov, Julia Casado, Vidyanath Chaudhary, Chen Tan, Alexander Emmanuelli, Camilla Salvagno, Deepika Awasthi, Paolo Giovanelli, Eun Sil Park, Sung-Min Hwang, Tito A. Sandoval, and Chang-Suk Chae
- Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid enriched in the tumor microenvironment of immunosuppressive malignancies such as ovarian cancer. Although LPA enhances the tumorigenic attributes of cancer cells, the immunomodulatory activity of this phospholipid messenger remains largely unexplored. Here, we report that LPA operates as a negative regulator of type I interferon (IFN) responses in ovarian cancer. Ablation of the LPA-generating enzyme autotaxin (ATX) in ovarian cancer cells reprogrammed the tumor immune microenvironment, extended host survival, and improved the effects of therapies that elicit protective responses driven by type I IFN. Mechanistically, LPA sensing by dendritic cells triggered PGE2 biosynthesis that suppressed type I IFN signaling via autocrine EP4 engagement. Moreover, we identified an LPA-controlled, immune-derived gene signature associated with poor responses to combined PARP inhibition and PD-1 blockade in patients with ovarian cancer. Controlling LPA production or sensing in tumors may therefore be useful to improve cancer immunotherapies that rely on robust induction of type I IFN.Significance:This study uncovers that ATX–LPA is a central immunosuppressive pathway in the ovarian tumor microenvironment. Ablating this axis sensitizes ovarian cancer hosts to various immunotherapies by unleashing protective type I IFN responses. Understanding the immunoregulatory programs induced by LPA could lead to new biomarkers predicting resistance to immunotherapy in patients with cancer.See related commentary by Conejo-Garcia and Curiel, p. 1841.This article is highlighted in the In This Issue feature, p. 1825
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- 2023
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24. Supplementary Figure from Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer
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Juan R. Cubillos-Ruiz, Anniina Färkkilä, Alan D. D'Andrea, David Pépin, Dmitriy Zamarin, E. Alfonso Romero-Sandoval, Kevin Holcomb, Franck J. Barrat, Minkyung Song, Andrew V. Kossenkov, Julia Casado, Vidyanath Chaudhary, Chen Tan, Alexander Emmanuelli, Camilla Salvagno, Deepika Awasthi, Paolo Giovanelli, Eun Sil Park, Sung-Min Hwang, Tito A. Sandoval, and Chang-Suk Chae
- Abstract
Supplementary Figure from Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer
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- 2023
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25. Potential Anti-Mpox Virus Activity of Atovaquone, Mefloquine, and Molnupiravir, and Their Potential Use as Treatments
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Daisuke Akazawa, Hirofumi Ohashi, Takayuki Hishiki, Takeshi Morita, Shoya Iwanami, Kwang Su Kim, Yong Dam Jeong, Eun-Sil Park, Michiyo Kataoka, Kaho Shionoya, Junki Mifune, Kana Tsuchimoto, Shinjiro Ojima, Aa Haeruman Azam, Shogo Nakajima, Hyeongki Park, Tomoki Yoshikawa, Masayuki Shimojima, Kotaro Kiga, Shingo Iwami, Ken Maeda, Tadaki Suzuki, Hideki Ebihara, Yoshimasa Takahashi, and Koichi Watashi
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Infectious Diseases ,Immunology and Allergy - Abstract
Background Mpox virus (MPXV) is a zoonotic orthopoxvirus and caused an outbreak in 2022. Although tecovirimat and brincidofovir are approved as anti-smallpox drugs, their effects in mpox patients have not been well documented. In this study, by a drug repurposing approach, we identified potential drug candidates for treating mpox and predicted their clinical impacts by mathematical modeling. Methods We screened 132 approved drugs using an MPXV infection cell system. We quantified antiviral activities of potential drug candidates by measuring intracellular viral DNA and analyzed the modes of action by time-of-addition assay and electron microscopic analysis. We further predicted the efficacy of drugs under clinical concentrations by mathematical simulation and examined combination treatment. Results Atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51–5.2 μM, which was more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted postentry processes. Atovaquone was suggested to exert its activity through inhibiting dihydroorotate dehydrogenase. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative mathematical simulations predicted that atovaquone can promote viral clearance in patients by 7 days at clinically relevant drug concentrations. Conclusions These data suggest that atovaquone would be a potential candidate for treating mpox.
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- 2023
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26. A Study on the Expression of Emotional Vocabulary in 3- to 5-Year-Old Infants
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Sun-Hee Kim, Eun-Sil Park, and Hye-Jung Shin
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- 2022
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27. Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group
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Chul Joo Lyu, Jae Young Lim, Hee Young Shin, Jung Yoon Choi, Bo Ram Kim, Hee Young Ju, Bin Cho, Keon Hee Yoo, Kyung Taek Hong, Ji Kyoung Park, Hyoung Jin Kang, Nack-Gyun Chung, Hee Jo Baek, Hoon Kook, Eun Sil Park, Jae Min Lee, Hyery Kim, Young Bae Choi, Jung Woo Han, Seung Min Han, Kyung Mi Park, Ji Yoon Kim, Eu Jeen Yang, Jae Wook Lee, Kyung-Nam Koh, Young Tak Lim, Ye Jee Shim, Seom Gim Kong, Ho Joon Im, Eun Jin Choi, Seongkoo Kim, Hong Hoe Koo, and Sang Kyu Park
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Male ,Acute promyelocytic leukemia ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Pediatric Cancer ,medicine.medical_treatment ,Antineoplastic Agents ,Tretinoin ,Disease-Free Survival ,Leukocyte Count ,Leukemia, Promyelocytic, Acute ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Republic of Korea ,Humans ,Medicine ,Child ,Survival rate ,Retrospective Studies ,Chemotherapy ,All-trans retinoic acid ,business.industry ,Cerebral infarction ,Incidence (epidemiology) ,Remission Induction ,Infant ,Myeloid leukemia ,Induction chemotherapy ,Retrospective cohort study ,Induction Chemotherapy ,medicine.disease ,Childhood ,Progression-Free Survival ,Treatment Outcome ,Oncology ,Child, Preschool ,Female ,Original Article ,business - Abstract
Purpose Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.Materials and Methods Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.Results Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.
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- 2022
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28. Identification of inosine monophosphate dehydrogenase as a potential target for anti-monkeypox virus agents
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Takayuki Hishiki, Takeshi Morita, Daisuke Akazawa, Hirofumi Ohashi, Eun-Sil Park, Michiyo Kataoka, Junki Mifune, Kaho Shionoya, Kana Tsuchimoto, Shinjiro Ojima, Aa Haeruman Azam, Shogo Nakajima, Tomoki Yoshikawa, Masayuki Shimojima, Kotaro Kiga, Ken Maeda, Tadaki Suzuki, Hideki Ebihara, Yoshimasa Takahashi, and Koichi Watashi
- Abstract
Monkeypox virus (MPXV) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation. These compounds showed broad-spectrum anti-orthopoxvirus activities and presented lower 90% inhibitory concentrations (0.032-1.40 μM) than brincidofovir, an approved anti-smallpox agent. These three compounds have been suggested to target the post-entry step to reduce the intracellular production of virions. Knockdown of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme of guanosine biosynthesis and a target of MPA, dramatically reduced MPXV DNA production. Moreover, supplementation with guanosine recovered the anti-MPXV effect of MPA, suggesting that IMPDH and its guanosine biosynthetic pathway regulate MPXV replication. By targeting IMPDH, we identified a series of compounds with stronger anti-MPXV activity than MPA. These evidences propose that IMPDH is a potential target for the development of anti-MPXV agents.ImportanceMonkeypox is a zoonotic disease caused by infection with the monkeypox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against monkeypox in the United States. Although brincidofovir and tecovirimat are drugs approved for the treatment of smallpox by the U.S. Food and Drug Administration, their efficacy against monkeypox has not been established. Moreover, these drugs may present negative side effects. Therefore, new anti-monkeypox virus agents are needed. This study revealed that gemcitabine, trifluridine, and mycophenolic acid inhibited monkeypox virus propagation, exhibited broad-spectrum anti-orthopoxvirus activities. We also suggested inosine monophosphate dehydrogenase as a potential target for the development of anti-monkeypox virus agents. By targeting this molecule, we identified a series of compounds with stronger anti-monkeypox virus activity than mycophenolic acid.
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- 2022
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29. A novel nairovirus associated with acute febrile illness in Hokkaido, Japan
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Masahiro Miyoshi, Ryo Nakao, Yukari Itakura, Yurino Terauchi, Rika Komagome, Chiaki Funaki, Atsushi Nagasaka, Hiroki Yamaguchi, Hirofumi Sawa, Eun-Sil Park, Takuya Ito, Yoshihiro Sakoda, Katsunori Okazaki, Akiko Goto, Ken Maeda, Shunji Edagawa, Kentaro Yoshii, Yasuko Orba, Kango Tatemoto, Hiroaki Kariwa, Keita Matsuno, Keita Mizuma, Asako Shigeno, Fumihiro Kodama, Mariko Sashika, Kimiaki Yamano, Lesley Bell-Sakyi, Masayuki Saijo, Katsuro Hagiwara, and Mariko Ishizuka
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Adult ,Male ,Ixodes ricinus ,Fever ,Science ,General Physics and Astronomy ,Genome, Viral ,Biology ,Tick ,Antibodies, Viral ,Article ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Serology ,Leukocyte Count ,Viral reservoirs ,Japan ,Borrelia ,parasitic diseases ,medicine ,Animals ,Humans ,Pathogen ,Phylogeny ,Nairovirus ,Multidisciplinary ,Leukopenia ,Ixodes ,Virion ,General Chemistry ,Middle Aged ,biology.organism_classification ,Virology ,Viral infection ,RNA, Viral ,medicine.symptom ,Viral pathogenesis - 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., Here, Kodama et al. describe the discovery, isolation and characterization of a novel tick-borne orthonairovirus, designated Yezo virus (YEZV), from patients with an acute febrile illness in Japan. Serological testing of wildlife and molecular screening of ticks suggest an endemic circulation of YEZV in Japan.
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- 2021
30. A Study on the New Paradigm Prospects for the Korean Pop Music Industry: Focusing on the Live Concerts Since the Post-COVID Era
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Young Joo Lee and Eun sil Park
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Popular music ,History ,Visual arts - Published
- 2021
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31. Tumor-derived Lysophosphatidic Acid Blunts Protective Type-I Interferon Responses in Ovarian Cancer
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Chang-Suk Chae, Tito A. Sandoval, Sung-Min Hwang, Eun Sil Park, Paolo Giovanelli, Deepika Awasthi, Camilla Salvagno, Alexander Emmanuelli, Chen Tan, Vidyanath Chaudhary, Julia Casado, Andrew V. Kossenkov, Minkyung Song, Franck J. Barrat, Kevin Holcomb, E. Alfonso Romero-Sandoval, Dmitriy Zamarin, David Pépin, Alan D. D'Andrea, Anniina Färkkilä, and Juan R. Cubillos-Ruiz
- Subjects
Oncology ,Article - Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid enriched in the tumor microenvironment of immunosuppressive malignancies such as ovarian cancer. Although LPA enhances the tumorigenic attributes of cancer cells, the immunomodulatory activity of this phospholipid messenger remains largely unexplored. Here, we report that LPA operates as a negative regulator of type I interferon (IFN) responses in ovarian cancer. Ablation of the LPA-generating enzyme autotaxin (ATX) in ovarian cancer cells reprogrammed the tumor immune microenvironment, extended host survival, and improved the effects of therapies that elicit protective responses driven by type I IFN. Mechanistically, LPA sensing by dendritic cells triggered PGE2 biosynthesis that suppressed type I IFN signaling via autocrine EP4 engagement. Moreover, we identified an LPA-controlled, immune-derived gene signature associated with poor responses to combined PARP inhibition and PD-1 blockade in patients with ovarian cancer. Controlling LPA production or sensing in tumors may therefore be useful to improve cancer immunotherapies that rely on robust induction of type I IFN. Significance: This study uncovers that ATX–LPA is a central immunosuppressive pathway in the ovarian tumor microenvironment. Ablating this axis sensitizes ovarian cancer hosts to various immunotherapies by unleashing protective type I IFN responses. Understanding the immunoregulatory programs induced by LPA could lead to new biomarkers predicting resistance to immunotherapy in patients with cancer. See related commentary by Conejo-Garcia and Curiel, p. 1841. This article is highlighted in the In This Issue feature, p. 1825
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- 2022
32. Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments
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Daisuke Akazawa, Hirofumi Ohashi, Takayuki Hishiki, Takeshi Morita, Shoya Iwanami, Kwang Su Kim, Yong Dam Jeong, Eun-Sil Park, Michiyo Kataoka, Kaho Shionoya, Junki Mifune, Kana Tsuchimoto, Shinjiro Ojima, Aa Haeruman Azam, Shogo Nakajima, Hyeongki Park, Tomoki Yoshikawa, Masayuki Shimojima, Kotaro Kiga, Shingo Iwami, Ken Maeda, Tadaki Suzuki, Hideki Ebihara, Yoshimasa Takahashi, and Koichi Watashi
- Abstract
Monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes smallpox-like symptoms in humans and caused an outbreak in May 2022 that led the WHO to declare global health emergency. In this study, from a screening of approved-drug libraries using an MPXV infection cell system, atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51-5.2 μM, which is more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted post-entry process to impair intracellular virion accumulation. Inhibitors of dihydroorotate dehydrogenase, an atovaquone’s target enzyme, showed conserved anti-MPXV activities. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative mathematical simulations predicted that atovaquone can promote viral clearance in patients by seven days at clinically relevant drug concentrations. Moreover, atovaquone and molnupiravir exhibited pan-Orthopoxvirus activity against vaccinia and cowpox viruses. These data suggest that atovaquone would be potential candidates for treating monkeypox.
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- 2022
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33. Effect of Group Intervention Using Emoticons on Emotional Empathy and Conversational Function of School-Age Children With Intellectual Disabilities
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Hye Jung Shin, Eun Sil Park, and Hye Young Han
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School age child ,Emotional empathy ,media_common.quotation_subject ,Group intervention ,Psychology ,Function (engineering) ,Developmental psychology ,media_common - Published
- 2021
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34. A retrospective survey of the seroprevalence of severe fever with thrombocytopenia syndrome virus in wild animals in Japan
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Akitoyo Hotta, Masanobu Kimura, Ayaka Okada, Eun-Sil Park, Shigeru Morikawa, and Yasuo Inoshima
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Phlebovirus ,Animals, Wild ,Japan ,Seroepidemiologic Studies ,Retrospective survey ,Case fatality rate ,Prevalence ,medicine ,Animals ,Seroprevalence ,Retrospective Studies ,Mammals ,lcsh:Veterinary medicine ,General Veterinary ,biology ,seroprevalence ,business.industry ,SFTS virus ,medicine.disease ,Serum samples ,biology.organism_classification ,Virology ,wild animal ,Severe fever with thrombocytopenia syndrome ,biology.protein ,lcsh:SF600-1100 ,Original Article ,Antibody ,business ,Severe fever with thrombocytopenia syndrome virus ,severe fever with thrombocytopenia syndrome - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) has a high fatality rate and is caused by SFTS virus (SFTSV). Currently, SFTS is endemic to some areas in western Japan, and wild animals are considered to play important roles in the circulation of SFTSV in the environment. Previous retrospective surveys using samples mainly obtained between 2006 and 2015 revealed serological evidence of SFTSV infection in wild animals; however, seroprevalence before 2006 remains unclear. In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas., In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas.
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- 2021
35. The Optimal Time for Initiating Probiotics for Preterm and Very-Low-Birth-Weight Infants: A 10-Year Experience in a Single Neonatal Intensive Care Unit.
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JeongHoon Park, Jae Young Cho, Jung Sook Yeom, Jin Su Jun, Ji Sook Park, Eun Sil Park, Ji Hyun Seo, Jae Young Lim, Chan-Hoo Park, and Hyang-Ok Woo
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NEONATAL intensive care units ,PREMATURE infants ,NEONATAL sepsis ,VERY low birth weight ,PROBIOTICS ,BIRTH weight - Abstract
Purpose: The starting time for probiotic supplementation in preterm infants after birth varies widely. This study aimed to investigate the optimal time for initiating probiotics to reduce adverse outcomes in preterm or very low birth weight (VLBW) infants. Methods: Medical records of preterm infants born at a gestational age (GA) of <32 weeks or VLBW infants in 2011-2020 were reviewed respectively. The infants who received Saccharomyces boulardii probiotics within 7 days of birth were grouped into an early introduction (EI) group, and those who received supplemented probiotics after 7 days of birth were part of the late introduction (LI) group. Clinical characteristics were compared between the two groups and analyzed statistically. Results: A total of 370 infants were included. The mean GA (29.1 weeks vs. 31.2 weeks, p<0.001) and birth weight (1,235.9 g vs. 1491.4 g, p<0.001) were lower in the LI group (n=223) than in the EI group. The multivariate analysis indicated that factors affecting the LI of probiotics were GA at birth (odds ratio [OR], 1.52; p<0.001) and the enteral nutrition start day (OR, 1.47; p<0.001). The late probiotic introduction was associated with a risk of late-onset sepsis (OR, 2.85; p=0.020), delayed full enteral nutrition (OR, 5.44; p<0.001), and extrauterine growth restriction (OR, 1.67; p=0.033) on multivariate analyses after adjusting for GA. Conclusion: Early supplementation of probiotics within a week after birth may reduce adverse outcomes among preterm or VLBW infants. [ABSTRACT FROM AUTHOR]
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- 2023
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36. A Case of Nephrogenic Diabetes Insipidus with a Rare X-linked Recessive Mutation in an Infant with Developmental and Growth Retardation Tracked by the Korean National Health Screening Program
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Ji Hyun Seo, Jae Young Cho, Ji Sook Park, Min-Ji Kim, Hyang Ok Woo, Jae Young Lim, Hee-Shang Youn, and Eun Sil Park
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National health ,medicine.medical_specialty ,Growth retardation ,business.industry ,Nephrogenic diabetes insipidus ,medicine.disease ,Endocrinology ,Internal medicine ,Arginine vasopressin receptor 2 ,Mutation (genetic algorithm) ,General Earth and Planetary Sciences ,Medicine ,business ,X-linked recessive inheritance ,General Environmental Science - Published
- 2020
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37. Report: central diabetes insipidus and schwannoma in a male with X-linked congenital adrenal hypoplasia
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Ji Sook Park, Jae Young Cho, Ji Hyun Seo, Jae Young Lim, Hyang Ok Woo, Eun Sil Park, Seul Ah. Jeong, Hee-Shang Youn, and Boo Kyeong Seo
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0301 basic medicine ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Schwannoma ,Endocrinology, Diabetes and Metabolism ,Case Report ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Polyuria ,Hypogonadotropic hypogonadism ,030225 pediatrics ,X-linked adrenal hypoplasia congenita ,medicine ,Adrenal insufficiency ,Humans ,Central diabetes insipidus ,lcsh:RC648-665 ,Base Sequence ,business.industry ,DAX-1 Orphan Nuclear Receptor ,Infant ,General Medicine ,medicine.disease ,Adrenal hypoplasia congenita ,Diabetes Insipidus, Neurogenic ,030104 developmental biology ,Hypoadrenocorticism, Familial ,Congenital adrenal hypoplasia ,Diabetes insipidus ,DAX1 ,medicine.symptom ,business ,Polydipsia ,Neurilemmoma - Abstract
Background DAX1 mutations are related to the X-linked form of adrenal hypoplasia congenita (AHC) in infancy and to hypogonadotropic hypogonadism (HH) in puberty. We report a male patient affected by X-linked AHC who presented with central diabetes insipidus and schwannoma in adulthood, which has not been described in association with AHC. Case presentation A 36-day-old male infant who presented with severe dehydration was admitted to the intensive care unit. His laboratory findings showed hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis. After hormonal evaluation, he was diagnosed with adrenal insufficiency, and he recovered after treatment with hydrocortisone and a mineralocorticoid. He continued to take hydrocortisone and the mineralocorticoid after discharge. At the age of 17, he did not show any signs of puberty. On the basis of a GnRH test, a diagnosis of HH was made. At the age of 24, he was hospitalized with thirst, polydipsia and polyuria. He underwent a water deprivation test for polydipsia and was diagnosed with central diabetes insipidus. By quantitative polymerase chain reaction analysis, we identified a hemizygous frameshift mutation in DAX1 (c.543delA). Conclusions We suggest that DAX1 mutations affect a wider variety of endocrine organs than previously known, including the posterior pituitary gland.
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- 2020
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38. Diagnosis of severe fever with thrombocytopenia syndrome (SFTS) in a cat with clinical findings resembling lymphoma
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Mitsuhiro IRIE, Takuma MIYOSHI, Akira HIRAMOTO, Masahiko HIRATA, Masamine TAKANOSU, Eun-Sil PARK, and Ken MAEDA
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Male ,Phlebovirus ,General Veterinary ,Lymphoma ,Severe Fever with Thrombocytopenia Syndrome ,Cats ,Animals ,Cat Diseases - Abstract
A two-year-old male domestic cat showed lethargy, tonic-clonic convulsion, and mucosal jaundice. Upon admission, blood examination indicated severe neutropenia and thrombocytopenia, and ultrasonography revealed diffuse splenomegaly with a honeycomb appearance and abdominal lymph nodes enlargement in addition to a decrease in cardiac blood flow indicating a shock condition. Cytology of the spleen showed a cell population composed of immature large lymphoid cells with distinct nucleoli, suggesting lymphoma. The cat received symptomatic treatments but died four hours later. Reverse transcriptase polymerase chain reaction assay of the spleen sample indicated the presence of severe fever with thrombocytopenia syndrome (SFTS) virus S gene segment. Clinical features of this case that was diagnose as SFTS were similar to lymphoma. Therefore, pet owners and veterinary workers should be protected against infection of SFTS.
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- 2022
39. Reverse Genetics System for Heartland Bandavirus: NSs Protein Contributes to Heartland Bandavirus Virulence
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Satoshi Taniguchi, Takuya Inagaki, Shigeru Tajima, Tadaki Suzuki, Tomoki Yoshikawa, Shuetsu Fukushi, Eun-Sil Park, Hikaru Fujii, Shigeru Morikawa, Hideki Tani, Eri Nakayama, Takahiro Maeki, Masayuki Shimojima, Chang-Kweng Lim, and Masayuki Saijo
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Diarrhea ,Phlebovirus ,Virulence ,Virulence Factors ,Bunyaviridae ,Immunology ,Headache ,Nausea ,Viral Nonstructural Proteins ,Microbiology ,Antiviral Agents ,Arthralgia ,Immunity, Innate ,Recombinant Proteins ,Reverse Genetics ,Genome Replication and Regulation of Viral Gene Expression ,Mice ,Virology ,Insect Science ,Animals ,Humans ,Fatigue ,Signal Transduction - Abstract
Heartland bandavirus (HRTV), which is an emerging tick-borne virus first identified in Missouri in 2009, causes fever, fatigue, decreased appetite, headache, nausea, diarrhea, and muscle or joint pain in humans. HRTV is genetically close to Dabie bandavirus, which is the causative agent of severe fever with thrombocytopenia syndrome (SFTS) in humans and is known as SFTS virus (SFTSV). The generation of infectious HRTV entirely from cloned cDNAs has not yet been reported. The absence of a reverse genetics system for HRTV has delayed efforts to understand its pathogenesis and to generate vaccines and antiviral drugs. Here, we developed a reverse genetics system for HRTV, which employs an RNA polymerase I-mediated expression system. A recombinant nonstructural protein (NSs)-knockout HRTV (rHRTV-NSsKO) was generated. We found that NSs interrupted signaling associated with innate immunity in HRTV-infected cells. The rHRTV-NSsKO was highly attenuated, indicated by the apparent absence of symptoms in a mouse model of HRTV infection. Moreover, mice immunized with rHRTV-NSsKO survived a lethal dose of HRTV. These findings suggest that NSs is a virulence factor of HRTV and that rHRTV-NSsKO could be a vaccine candidate for HRTV. IMPORTANCE Heartland bandavirus (HRTV) is a tick-borne virus identified in the United States in 2009. HRTV causes fever, fatigue, decreased appetite, headache, nausea, diarrhea, and muscle or joint pain in humans. FDA-approved vaccines and antiviral drugs are unavailable. The lack of a reverse genetics system hampers efforts to develop such antiviral therapeutics. Here, we developed a reverse genetics system for HRTV that led to the generation of a recombinant nonstructural protein (NSs)-knockout HRTV (rHRTV-NSsKO). We found that NSs interrupted signaling associated with innate immunity in HRTV-infected cells. Furthermore, rHRTV-NSsKO was highly attenuated and immunogenic in a mouse model. These findings suggest that NSs is a virulence factor of HRTV and that rHRTV-NSsKO could be a vaccine candidate for HRTV.
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- 2022
40. Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data
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Kyung-Nam, Koh, Jung Woo, Han, Hyoung Soo, Choi, Hyoung Jin, Kang, Ji Won, Lee, Keon Hee, Yoo, Ki Woong, Sung, Hong Hoe, Koo, Kyung Taek, Hong, Jung Yoon, Choi, Sung Han, Kang, Hyery, Kim, Ho Joon, Im, Seung Min, Hahn, Chuhl Joo, Lyu, Hee-Jo, Baek, Hoon, Kook, Kyung Mi, Park, Eu Jeen, Yang, Young Tak, Lim, Seongkoo, Kim, Jae Wook, Lee, Nack-Gyun, Chung, Bin, Cho, Meerim, Park, Hyeon Jin, Park, Byung-Kiu, Park, Jun Ah, Lee, Jun Eun, Park, Soon Ki, Kim, Ji Yoon, Kim, Hyo Sun, Kim, Youngeun, Ma, Kyung Duk, Park, Sang Kyu, Park, Eun Sil, Park, Ye Jee, Shim, Eun Sun, Yoo, Kyung Ha, Ryu, Jae Won, Yoo, Yeon Jung, Lim, Hoi Soo, Yoon, Mee Jeong, Lee, Jae Min, Lee, In-Sang, Jeon, Hye Lim, Jung, Hee Won, Chueh, and Seunghyun, Won
- Abstract
Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea.From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed.Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p0.001).The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.
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- 2022
41. Oncogenic Events Dictate the Types and Locations of Gynecological Malignancies Originating from Krt8+ Mesothelial and Müllerian-Derived Epithelial Cells
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Eun-Sil Park, Dongxi Xiang, Ying Xie, Roderick T. Bronson, and Zhe Li
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Müllerian-derived epithelial cells ,Cancer Research ,ovarian cancer ,uterine cancer ,mouse modeling ,cellular origin ,Keratin 8 (K8) ,mesothelial cells ,ovarian surface epithelial (OSE) cells ,fallopian tube epithelial (FTE) cells ,endometrial cells ,Oncology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and/or Müllerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN/PI3K, RAS, and WNT pathways. However, how these mutations and their corresponding deregulated pathways affect gynecological cancer development from their cells-of-origin remains largely elusive. To address this, we performed the intrabursal injection of Cre-expressing adenovirus under the control of Krt8 promoter (Ad-K8-Cre) to mice carrying combinations of various conditional alleles for cancer genes. We found that Ad-K8-Cre specifically targeted mesothelial cells, including ovarian surface epithelial (OSE) cells (mainly the LGR5+ subset of OSE cells) and mesothelial cells lining the fallopian tube (FT) serosa; the injected Ad-K8-Cre also targeted Müllerian-derived epithelial cells, including FT epithelial cells and uterine endometrial epithelial cells. The loss of p53 may preferentially affect Müllerian-derived epithelial cells, leading to the development of uterine and ovarian malignancies, whereas PTEN-loss may preferentially affect mesothelial cells, leading to the development of ovarian endometrioid malignancies (upon KRAS-activation or APC-loss) or adenoma on the FT surface (upon DICER-loss). Overall, our data suggest that different Krt8+ mesothelial and epithelial cell types in the female reproductive system may have different sensitivities toward oncogenic mutations and, as a result, oncogenic events may dominantly determine the locations and types of the gynecological malignancies developed from them.
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- 2022
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42. Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants
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Sho Miyamoto, Takeshi Arashiro, Yu Adachi, Saya Moriyama, Hitomi Kinoshita, Takayuki Kanno, Shinji Saito, Harutaka Katano, Shun Iida, Akira Ainai, Ryutaro Kotaki, Souichi Yamada, Yudai Kuroda, Tsukasa Yamamoto, Keita Ishijima, Eun-Sil Park, Yusuke Inoue, Yoshihiro Kaku, Minoru Tobiume, Naoko Iwata-Yoshikawa, Nozomi Shiwa-Sudo, Kenzo Tokunaga, Seiya Ozono, Takuya Hemmi, Akira Ueno, Noriko Kishida, Shinji Watanabe, Kiyoko Nojima, Yohei Seki, Takuo Mizukami, Hideki Hasegawa, Hideki Ebihara, Ken Maeda, Shuetsu Fukushi, Yoshimasa Takahashi, and Tadaki Suzuki
- Subjects
COVID-19 Vaccines ,Postoperative Complications ,SARS-CoV-2 ,Vaccination ,COVID-19 ,Humans ,General Medicine ,Antibodies, Viral ,BNT162 Vaccine - Abstract
SUMMARYBackgroundThe immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories.MethodsThe neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination.FindingsThe Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies.ConclusionsImmune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants.FundingThis study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
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- 2022
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43. Oncogenic Events Dictate the Types and Locations of Gynecological Malignancies Originating from
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Eun-Sil, Park, Dongxi, Xiang, Ying, Xie, Roderick T, Bronson, and Zhe, Li
- Abstract
Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and/or Müllerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN/PI3K, RAS, and WNT pathways. However, how these mutations and their corresponding deregulated pathways affect gynecological cancer development from their cells-of-origin remains largely elusive. To address this, we performed the intrabursal injection of Cre-expressing adenovirus under the control of
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- 2021
44. Neutralizing-antibody-independent SARS-CoV-2 control correlated with intranasal-vaccine-induced CD8
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Hiroshi Ishii, Takushi Nomura, Hiroyuki Yamamoto, Masako Nishizawa, Trang Thi Thu Hau, Shigeyoshi Harada, Sayuri Seki, Midori Nakamura-Hoshi, Midori Okazaki, Sachie Daigen, Ai Kawana-Tachikawa, Noriyo Nagata, Naoko Iwata-Yoshikawa, Nozomi Shiwa, Tadaki Suzuki, Eun-Sil Park, Maeda Ken, Taishi Onodera, Yoshimasa Takahashi, Kohji Kusano, Ryutaro Shimazaki, Yuriko Suzaki, Yasushi Ami, and Tetsuro Matano
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Male ,COVID-19 Vaccines ,Coronavirus M Proteins ,viruses ,CD8-Positive T-Lymphocytes ,Antibodies, Viral ,General Biochemistry, Genetics and Molecular Biology ,Coronavirus Envelope Proteins ,Report ,vaccine ,Chlorocebus aethiops ,Animals ,Coronavirus Nucleocapsid Proteins ,Pandemics ,Vero Cells ,Administration, Intranasal ,SARS-CoV-2 ,viral vector ,Vaccination ,COVID-19 ,Viral Load ,Phosphoproteins ,Antibodies, Neutralizing ,Disease Models, Animal ,Macaca fascicularis ,Treatment Outcome ,variant ,Spike Glycoprotein, Coronavirus ,Female ,CD8+ T cell - 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 investigate the efficacy of an intranasal vaccine expressing viral non-S antigens against intranasal SARS-CoV-2 challenge in cynomolgus macaques. Seven vaccinated macaques exhibit 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 is 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., Graphical Abstract, Ishii et al. show neutralization-independent SARS-CoV-2 control associated with vaccine-induced CD8+ T-cell responses, indicating that virus-specific CD8+ T-cell induction by intranasal vaccination can result in SARS-CoV-2 control. Results highlight the potential of vaccine-induced CD8+ T-cell responses to contribute to the control of SARS-CoV-2 variants.
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- 2021
45. Thymic precursor cells generate acute myeloid leukemia in NUP98-PHF23/NUP98-HOXD13 double transgenic mice
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Robert L. Walker, Vijay Negi, Yang Jo Chung, Paul S. Meltzer, Subhadip Kundu, Yuelin J. Zhu, Eun Sil Park, and Peter D. Aplan
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0301 basic medicine ,Myeloid ,Transgene ,lcsh:Medicine ,Mice, Transgenic ,Biology ,Article ,Acute myeloid leukaemia ,03 medical and health sciences ,Mice ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,lcsh:Science ,Cancer genetics ,Homeodomain Proteins ,Multidisciplinary ,Thymocytes ,lcsh:R ,Myeloid leukemia ,medicine.disease ,3. Good health ,Transplantation ,Nuclear Pore Complex Proteins ,Leukemia ,Thymocyte ,Haematopoiesis ,Leukemia, Myeloid, Acute ,030104 developmental biology ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,030220 oncology & carcinogenesis ,Cancer research ,lcsh:Q ,Bone marrow ,Stem Cell Transplantation ,Transcription Factors - Abstract
Transgenic mice that express either a NUP98–PHF23 (NP23) or NUP98-HOXD13 (NHD13) fusion in the hematopoietic compartment develop a wide spectrum of leukemias, including myeloid, erythroid, megakaryocytic and lymphoid, at age 9–14 months. NP23-NHD13 double transgenic mice were generated by interbreeding NP23 and NHD13 mice. Remarkably, 100% of the NP23-NHD13 double transgenic mice developed acute myeloid leukemia (AML) within three months, characterized by replacement of the thymus with leukemic myeloblasts. The marked infiltration of thymus led to the intriguing hypothesis that AML generated in NP23-NHD13 mice arose in the thymus, as opposed to the bone marrow (BM). Transplantation of CD4-CD8- double negative (DN) thymocytes (which were also negative for Mac1 and Gr1) from leukemic NHD13/NP23 mice demonstrated that DN thymocytes could transmit AML, and limiting dilution studies showed that leukemia initiating cells were increased 14-fold in the thymus compared to BM. Further thymocyte fractionation demonstrated that DN1 and DN2, but not DN3 or DN4 fractions transmitted AML, and a marked expansion (100-fold) of Lineage-Sca1 + Kit + (LSK) cells in the thymus of the NP23-NHD13 mice. Taken together, these results show that the thymus of NP23-NHD13 mice acts as a reservoir for AML initiating cells and that thymic progenitors can transmit AML.
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- 2019
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46. Severe Fever with Thrombocytopenia Syndrome Phlebovirus causes lethal viral hemorrhagic fever in cats
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Takeshi Kurosu, Tadaki Suzuki, Tomoki Yoshikawa, Akiko Okutani, Koichi Imaoka, Shuetsu Fukushi, Naoko Iwata-Yoshikawa, Yasushi Ami, Masanobu Kimura, Masayuki Saijo, Shumpei Watanabe, Shigeru Morikawa, Masayuki Shimojima, Hideki Hasegawa, Ken Maeda, Noriyo Nagata, Michiyo Kataoka, Eun sil Park, and Ken-Ichi Hanaki
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Phlebovirus ,0301 basic medicine ,Hemorrhagic Fevers, Viral ,Biopsy ,lcsh:Medicine ,Viral transmission ,Cat Diseases ,Article ,Viral hemorrhagic fever ,03 medical and health sciences ,0302 clinical medicine ,Leukocytopenia ,medicine ,Animals ,lcsh:Science ,Multidisciplinary ,CATS ,biology ,business.industry ,lcsh:R ,Viral host response ,Jaundice ,biology.organism_classification ,medicine.disease ,Virology ,Hemorrhagic Fevers ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,Cats ,lcsh:Q ,Disease Susceptibility ,Symptom Assessment ,medicine.symptom ,Hemophagocytosis ,business ,Biomarkers ,030217 neurology & neurosurgery ,Viral pathogenesis - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by the SFTS phlebovirus (SFTSV). SFTS patients were first reported in China, followed by Japan and South Korea. In 2017, cats were diagnosed with SFTS for the first time, suggesting that these animals are susceptible to SFTSV. To confirm whether or not cats were indeed susceptible to SFTSV, animal subjects were experimentally infected with SFTSV. Four of the six cats infected with the SPL010 strain of SFTSV died, all showing similar or more severe symptoms than human SFTS patients, such as a fever, leukocytopenia, thrombocytopenia, weight loss, anorexia, jaundice and depression. High levels of SFTSV RNA loads were detected in the serum, eye swab, saliva, rectal swab and urine, indicating a risk of direct human infection from SFTS-infected animals. Histopathologically, acute necrotizing lymphadenitis and hemophagocytosis were prominent in the lymph nodes and spleen. Severe hemorrhaging was observed throughout the gastrointestinal tract. B cell lineage cells with MUM-1 and CD20, but not Pax-5 in the lesions were predominantly infected with SFTSV. The present study demonstrated that cats were highly susceptible to SFTSV. The risk of direct infection from SFTS-infected cats to humans should therefore be considered.
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- 2019
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47. Establishment of an immunofluorescence assay to detect IgM antibodies to Nipah virus using HeLa cells expressing recombinant nucleoprotein
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Hui Min Neoh, Akira Noguchi, Shigeru Morikawa, Catalino S. Demetria, Fedelino F. Malbas, Eun sil Park, Yoshihiro Kaku, Satoshi Inoue, Ross A. Lunt, and A. Rahman A. Jamal
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0301 basic medicine ,030106 microbiology ,Antibodies, Viral ,Immunofluorescence ,law.invention ,Serology ,03 medical and health sciences ,Blood serum ,Antigen ,law ,Virology ,parasitic diseases ,medicine ,Animals ,Humans ,Serologic Tests ,Fluorescent Antibody Technique, Indirect ,Direct fluorescent antibody ,Henipavirus Infections ,medicine.diagnostic_test ,biology ,Nipah Virus ,Recombinant Proteins ,Titer ,030104 developmental biology ,Immunoglobulin M ,biology.protein ,Recombinant DNA ,Macaca ,Capsid Proteins ,Antibody ,HeLa Cells - Abstract
A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.
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- 2019
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48. A Multicenter Study on von Willebrand Disease Realities in Yeungnam Region
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Hyun-Ju Kim, Ye Jee Shim, Jae Min Lee, Sang Kyu Park, Eun Jin Choi, Hyo Sun Kim, Eu Jeen Yang, Seom Gim Kong, Eun Sil Park, Ji Kyoung Park, Young Tak Lim, Kyung Mi Park, Ji Yoon Kim, and Hee Won Chueh
- Subjects
lcsh:Internal medicine ,medicine.medical_specialty ,business.industry ,korea ,lcsh:RJ1-570 ,lcsh:Pediatrics ,Retrospective cohort study ,General Medicine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,von willebrand disease ,retrospective studies ,children ,Multicenter study ,hemic and lymphatic diseases ,Internal medicine ,adults ,Von Willebrand disease ,medicine ,lcsh:RC31-1245 ,business - Abstract
Background : : von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. Methods : : Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. Results : : Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). Conclusion : : A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.
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- 2019
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49. Monocyte Chemoattractant Protein (MCP)-1 in Rotavirus-Associated White Matter Injury in Newborns
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Young-Soo Kim, Ju Young Chung, Jae Young Lim, Eun Sil Park, Ji Hyun Seo, Chan-Hoo Park, Tae Hee Han, Ji Sook Park, Jae-Young Jo, Hyang Ok Woo, Hee-Shang Youn, and Jung Sook Yeom
- Subjects
Male ,Rotavirus ,0301 basic medicine ,030105 genetics & heredity ,medicine.disease_cause ,Rotavirus Infections ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Leukoencephalopathies ,Interferon ,medicine ,Causes of seizures ,Humans ,Macrophage ,Chemokine CCL2 ,business.industry ,Monocyte ,Infant, Newborn ,Brain ,Interleukin ,General Medicine ,White Matter ,Diffusion Magnetic Resonance Imaging ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Immunology ,Cytokines ,Female ,Tumor necrosis factor alpha ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Recent reports have suggested an association between rotavirus infection and a distinctive pattern of white matter injury (WMI) in neonates with seizures; however, the connection between the two is not fully understood. To evaluate the underlying mechanism, we profiled and compared eight cytokines (IL [interleukin]-1β, IL-6, IL-8, IL-10, IFN-γ [interferon-γ ], MCP-1 [monocyte chemoattractant protein-1], MIP-1β [macrophage inflammatory protein-1β], and TNF-α [tumor necrosis factor-α]) in the cerebrospinal fluid (CSF) of 33 neonates with seizures who had no other well-known causes of seizures and 13 control patients (rotavirus-induced gastroenteritis but without seizures). Among the 33 neonates with seizures, 9 showed WMI and all were infected with rotavirus (R + W + ). Among the 24 patients without WMI, 11 were infected with rotavirus (R + W − ) and 13 were not (R − W − ).Only MCP-1 and MIP-1β were different between the groups. MCP-1 was increased in R+ W+ compared with R + W− (p
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- 2019
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50. Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques
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Ai Kawana-Tachikawa, Tadaki Suzuki, Shigeyoshi Harada, Masako Nishizawa, Yasushi Ami, Takushi Nomura, Trang Thi Thu Hau, Naoko Iwata-Yoshikawa, Nozomi Shiwa, Yuriko Suzaki, Hiroshi Ishii, Sayuri Seki, Sachie Daigen, Noriyo Nagata, Harutaka Katano, Midori Okazaki, Ken Maeda, Eun-Sil Park, Midori Nakamura-Hoshi, Tetsuro Matano, Shun Iida, and Hiroyuki Yamamoto
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biology ,business.industry ,Virology ,Asymptomatic ,Immune system ,Viral replication ,Monoclonal ,biology.protein ,medicine ,Cytotoxic T cell ,Antibody ,medicine.symptom ,Neutralizing antibody ,business ,CD8 - Abstract
SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10-17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.Author SummarySARS-CoV-2 infection presents a wide spectrum of clinical manifestations ranging from asymptomatic to fatal respiratory failure. The determinants for failure in viral control and/or fatal disease progression have not been elucidated fully. Both acquired immune effectors, antibodies and CD8+ T cells, are considered to contribute to viral control. However, it remains unknown whether a deficiency in either of these two arms is directly linked to failure in the control of SARS-CoV-2 replication. In the present study, to know the requirement of CD8+ T cells for viral control after the establishment of infection, we examined the effect of CD8+ cell depletion by monoclonal anti-CD8 antibody administration in the subacute phase on SARS-CoV-2 replication in cynomolgus macaques. Unexpectedly, our analysis revealed no significant impact of CD8+ cell depletion on viral replication, indicating that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but this study suggests that CD8+ T-cell dysfunction may not solely lead to viral control failure or fatal disease progression.
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- 2021
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