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        Leptin Suppresses Glutamate-Induced Apoptosis Through Regulation of ERK1/2 Signaling Pathways in Rat Primary Astrocytes

        Park, Hyunju,Ahn, So-Hee,Jung, Yieun,Yoon, Joo Chun,Choi, Youn-Hee S. Karger AG 2017 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Vol.44 No.6

        <P>Background/Aims: Leptin is a hormone expressed by adipose tissue that regulates body energy homeostasis and weight loss by activating leptin receptors in the hypothalamus. Leptin receptors are also expressed in astrocytes. An anti-apoptosis effect of leptin in brain has recently been reported. However, the anti-apoptosis mechanism of leptin in the brain is unknown. Methods: To investigate whether leptin exerts protective effects against glutamate-induced apoptosis in astrocytes, we performed cell viability assays and apoptosis assays using rat primary astrocytes. Intracellular signaling pathways involved in anti-apoptosis effects of leptin were analyzed by immunoblotting together with a leptin mutant (S120A/T121A) with antagonist function and pharmacological inhibitors. Results: We found that glutamate-induced apoptosis in rat primary astrocytes was significantly decreased by treatment with leptin. Leptin inhibited glutamate-induced phosphorylation of ERK1/2 in astrocytes. The leptin S120A/T121A mutant did not inhibit glutamate-induced ERK1/2 phosphorylation and ERK1/2-mediated apoptosis. Conclusions: Collectively, our results provide initial evidence that leptin exerts an anti-apoptotic effect against glutamate toxicity through activation of intracellular signaling pathways which reverse glutamate-induced ERK1/2 phosphorylation in primary astrocytes. Therefore, our findings suggest that leptin might be considered a candidate for potential therapeutic applications in glutamate-induced brain excitotoxicity. (C) 2017 The Author(s) Published by S. Karger AG, Basel</P>

      • KCI등재

        Etiology of Bacteremia in Children With Hemato-Oncologic Diseases From 2013 to 2023: A Single Center Study

        Park Sun Woo,Park Ji Young,Choi Hyoung Soo,Lee Hyunju 대한소아감염학회 2024 Pediatric Infection and Vaccine Vol.31 No.1

        목적: 본 연구는 2013년부터 2023년까지 최근 10년간 분당서울대학교병원 소아 혈액종양 환자들에게 발생한 균혈증 발생 숫자를 확인하고, 원인균 발생 빈도 및 분포와 이들의 항생제 감수성을 분석하면서 경험적 항생제를 선택하는 데에 필요한 치료 지침의 기초 자료로 활용하고자 수행되었다. 방법: 2013년 1월부터 2023년 7월까지 분당서울대학교병원에 입원한 환자 중 기저혈액종양질환이 있으면서 혈류감염이발생한 환자들을 대상으로 후향적 의무기록 분석을 하였다. 결과: 10년의 연구 기간동안 총 74명의 환자에게서 98례의 혈류감염이 확인되었고, 이 중 그람 양성균, 그람 음성균, 진균이 각각 57.1% (n=56), 38.8% (n=38), 4.1% (n=4)이었다. 가장 흔한 그람 양성균은 coagulase-negative staphylococci (n=21, 21.4%) 와 Staphylococcus aureus (n=14, 14.3%) 였고, 가장 흔한 그람 음성균은 Klebsiella species (n=16, 16.3%) 와 Escherichia coli (n=10, 10.2%) 였다. 전체 사망한 환자들 중 균혈증 발생으로부터 30일 이내로 사망한 사례는 총 6건 (6.1%) 이었다. 결론: 본 연구는 혈액종양질환을 진단받은 소아 환아들에게서 발생한 균혈증의 원인균 분포 및 각 원인균의 항생제 분포를분석하였다. 연구결과를 토대로, 연구자들은 현재 사용하는 경험적 항생제 가이드라인을 유지할 수 있다는 점을 알 수 있었다. 소아 혈액종양질환 환아들에게서 발생한 균혈증에서 사용해야 할 적절한 경험적 항생제는 각 기관별로 조사한 항생제 감수성 양상에 기초하여 결정되어야 하며, 지속적인 모니터링은 반드시 이루어져야 한다 Purpose: This study aimed to identify the pathogens of bloodstream infection in children with underlying hemato-oncologic diseases, analyze susceptibility patterns, compare temporal trends with those of previous studies, and assess empirical antimicrobial therapy. Methods: Retrospective review study of children bacteremia in hemato-oncologic diseases was conducted at Seoul National University Bundang Hospital from January 2013 to July 2023. Results: Overall, 98 episodes of bacteremia were observed in 74 patients. Among pathogens isolated, 57.1% (n=56) were Gram-positive bacteria, 38.8% (n=38) were Gram-negative bacteria, and 4.1% (n=4) were Candida spp. The most common Gram-positive bacteria were coagulase-negative staphylococci (n=21, 21.4%) and Staphylococcus aureus, (n=14, 14.3%) whereas the most common Gram-negative bacteria were Klebsiella pneumoniae (n=16, 16.3%) and Escherichia coli (n=10, 10.2%). The susceptibility of Gram-positive bacteria to penicillin, oxacillin, and vancomycin was 11.5%, 32.7%, and 94.2%, respectively and the susceptibility of Gram-negative bacteria to cefotaxime, piperacillin/tazobactam, imipenem, gentamicin, and amikacin was 68.6%, 80%, 97.1%, 82.9%, and 91.4%, respectively. Methicillin-resistant S. aureus was detected in 1 strain and among Gram-negative strains, extended spectrum β-lactamase accounted for 28.9% (12/38). When analyzing the antibiotic susceptibility and empirical antibiotics, the mismatch rate was 25.5% (n=25). The mortality rate of children within 30 days of bacteremia was 7.1% (n=7). Conclusions: Empirical antibiotic therapy for bacteremia in children with hemato-oncologic diseases should be based on the local antibiogram in each institution and continuous monitoring is necessary.

      • SCIESCOPUSKCI등재

        Differential Game Based Air Combat Maneuver Generation Using Scoring Function Matrix

        Park, Hyunju,Lee, Byung-Yoon,Tahk, Min-Jea,Yoo, Dong-Wan The Korean Society for Aeronautical and Space Scie 2016 International Journal of Aeronautical and Space Sc Vol.17 No.2

        A differential game theory based approach is used to develop an automated maneuver generation algorithm for Within Visual Range (WVR) air-to-air combat of unmanned combat aerial vehicles (UCAVs). The algorithm follows hierarchical decisionmaking structure and performs scoring function matrix calculation based on differential game theory to find the optimal maneuvers against dynamic and challenging combat situation. The score, implying how much air superiority the UCAV has, is computed from the predicted relative geometry, relative distance and velocity of two aircrafts. Security strategy is applied at the decision-making step. Additionally, a barrier function is implemented to keep the airplanes above the altitude lower bound. To shorten the simulation time to make the algorithm more real-time, a moving horizon method is implemented. An F-16 pseudo 6-DOF model is used for realistic simulation. The combat maneuver generation algorithm is verified through three dimensional simulations.

      • SCIESCOPUSKCI등재

        Conessine Treatment Reduces Dexamethasone-Induced Muscle Atrophy by Regulating MuRF1 and Atrogin-1 Expression

        ( Hyunju Kim ),( Minsu Jang ),( Rackhyun Park ),( Daum Jo ),( Inho Choi ),( Joonho Choe ),( Won Keun Oh ),( Junsoo Park ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.4

        Conessine, a steroidal alkaloid, is a potent histamine H3 antagonist with antimalarial activity. We recently reported that conessine treatment interferes with H2O2-induced cell death by regulating autophagy. However, the cellular signaling pathways involved in conessine treatment are not fully understood. Here, we report that conessine reduces muscle atrophy by interfering with the expression of atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Promoter reporter assay revealed that conessine treatment inhibits FoxO3a-dependent transcription, NF-κB-dependent transcription, and p53-dependent transcription. We also showed by quantitative RT-PCR and western blot assays that conessine treatment reduced dexamethasone-induced expression of MuRF1 and atrogin-1. Finally, we demonstrated that conessine treatment reduced dexamethasone-induced muscle atrophy using differentiated C2C12 cells. These results collectively suggest that conessine is potentially useful in the treatment of muscle atrophy.

      • KCI등재

        Temporal association between the age-specific incidence of Guillain-Barré syndrome and SARS-CoV-2 vaccination in Republic of Korea: a nationwide time-series correlation study

        Hyunju Lee,Donghyok Kwon,Seoncheol Park,Seung Ri Park,Darda Chung,Jongmok Ha 질병관리본부 2023 Osong Public Health and Research Persptectives Vol.14 No.3

        Objectives: The incidence of Guillain-Barré syndrome (GBS) changed significantly during the coronavirus disease 2019 (COVID-19) pandemic. Emerging reports suggest that viral vector-based vaccines may be associated with an elevated risk of GBS.Methods: In this nationwide time-series correlation study, we examined the age-specific incidence of GBS from January 2011 to August 2022, as well as data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations and infections from February 2021 to August 2022. We compared the forecasted estimates of age-specific GBS incidence, using the pre-SARS-CoV-2 period as a benchmark, with the actual incidence observed during the post-vaccination period of the pandemic. Furthermore, we assessed the temporal association between GBS, SARS-CoV-2 vaccinations, and COVID-19 for different age groups.Results: In the age group of 60 and older, the rate ratio was significantly elevated during June-August and November 2021. A significant, strong positive association was observed between viral vector-based vaccines and GBS incidence trends in this age group (r=0.52, p=0.022). For the 30 to 59 years age group, the rate ratio was notably high in September 2021. A statistically significant, strong positive association was found between mRNA-based vaccines and GBS incidence in this age group (r=0.61, p=0.006).Conclusion: Viral vector-based SARS-CoV-2 vaccines were found to be temporally associated with an increased risk of GBS, particularly in older adults. To minimize age-specific and biological mechanism-specific adverse events, future vaccination campaigns should adopt a more personalized approach, such as recommending homologous mRNA-based SARS-CoV-2 vaccines for older adults to reduce the heightened risk of GBS.

      • KCI등재

        Increased Caveolin-2 Expression in Brain Endothelial Cells Promotes Age-Related Neuroinflammation

        Hyunju Park,Jung A Shin,Jiwoo Lim,Seulgi Lee,안정혁,Jihee Lee Kang,최윤희 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12

        Aging is a major risk factor for common neurodegenerative diseases. Although multiple molecular, cellular, structural, and functional changes occur in the brain during aging, the involvement of caveolin-2 (Cav-2) in brain ageing remains unknown. We investigated Cav-2 expression in brains of aged mice and its effects on endothelial cells. The human umbilical vein endothelial cells (HUVECs) showed decreased THP-1 adhesion and infiltration when treated with Cav-2 siRNA compared to control siRNA. In contrast, Cav-2 overexpression increased THP-1 adhesion and infiltration in HUVECs. Increased expression of Cav-2 and iba-1 was observed in brains of old mice. Moreover, there were fewer iba-1–positive cells in the brains of aged Cav-2 knockout (KO) mice than of wild-type aged mice. The levels of several chemokines were higher in brains of aged wild-type mice than in young wild-type mice; moreover, chemokine levels were significantly lower in brains of young mice as well as aged Cav-2 KO mice than in their wild-type counterparts. Expression of PECAM1 and VE-cadherin proteins increased in brains of old wild-type mice but was barely detected in brains of young wild-type and Cav-2 KO mice. Collectively, our results suggest that Cav-2 expression increases in the endothelial cells of aged brain, and promotes leukocyte infiltration and age-associated neuroinflammation.

      • Computer-aided design and growth of single-walled carbon nanotubes on 4in. wafers for electronic device applications

        Park, Serin,Park, Sohee,So, Hye-Mi,Jeon, Eun-Kyoung,Park, Dong-Won,Kim, Ju-Jin,Kim, Beom Soo,Kong, Ki-jeong,Chang, Hyunju,Lee, Jeong-O. Elsevier 2010 Carbon Vol.48 No.8

        <P><B>Abstract</B></P><P>We have employed computer-aided furnace design and process simulation to optimize the conditions under which single-walled carbon nanotubes (SWCNTs) may be grown in high yields on 4in. wafers for electronic device applications. Hydrokinetic simulations were performed to obtain optimized furnace structures and process conditions in terms of gas flow, temperature, and gas speed. Shower head structures and a flow isolation barrier were installed in an experimental 6in. furnace, as suggested by the hydrokinetic simulations. To ensure clean surfaces and uniform catalyst islands, catalyst patterns were lifted off using Au films or polydimethylsiloxane. Photolithography was used to fabricate field-effect transistors with SWCNTs grown on 4in. wafer substrates. The total yield of the nanotube devices increased from 30.5% to 96.4% after optimization.</P>

      • KCI등재

        Analysis of Critical COVID-19 Cases Among Children in Korea

        Hyunju Lee,Sujin Choi,Ji Young Park,Dae Sun Jo,Ui Yoon Choi,Hea Yon Lee,Yun Tae Jung,In Hyuk Chung,최영준,Jin Yong Kim,Young-Joon Park,Eun Hwa Choi 대한의학회 2022 Journal of Korean medical science Vol.37 No.1

        Background: Coronavirus disease 2019 (COVID-19) is generally asymptomatic or mild in otherwise healthy children, however, severe cases may occur. In this study, we report the clinical characteristics of children classified as critical COVID-19 in Korea to provide further insights into risk factors and management in children. Methods: This study was a retrospective case series of children < 18 years of age classified as critical COVID-19. Cases were identified by the Korea Disease Control and Prevention Agency surveillance system and medical records were reviewed. Critical COVID-19 was defined as cases with severe illness requiring noninvasive (high flow nasal cannula, continuous positive airway pressure, or bilevel positive airway pressure) or invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT), between January 20, 2020 and October 7, 2021. Results: Among 39,146 cases diagnosed with COVID-19 in subjects < 18 years of age, eight cases (0.02%) were identified as critical COVID-19. The median age was 13 years (range 10 month–17 years) and male-to-female ratio was 1:1. Three children had underlying diseases; one child has asthma and major depressive disorder, one child had LennoxGastaut syndrome and one child had mental retardation and was newly diagnosed with type 2 diabetes mellitus with the diagnosis of COVID-19. Among the eight children, seven were obese (body mass index range [BMI] median 29.3, range 25.9–38.2, weight-for-length > 97% for infant) and one was overweight (BMI 21.3). All patients had fever, six patients had dyspnea or cough and other accompanied symptoms included sore throat, headache, lethargy and myalgia. Radiologic findings showed pneumonia within 1–8 days after symptom onset. Pneumonia progressed in these children for 2–6 days and was improved within 5–32 days after diagnosis. Among the eight critical cases, remdesivir was administered in six cases. Steroids were provided for all cases. Inotropics were administered in one case. Six cases were treated with noninvasive mechanical ventilator and three required mechanical ventilator. One case required ECMO due to acute respiratory distress syndrome. All cases were admitted to the intensive care unit and admission period ranged from 9–39 days. Among all critical COVID-19 cases < 18 years of age, there were no fatal cases. Conclusion: To develop appropriate policies for children in the COVID-19 pandemic, it is important to monitor and assess the clinical burden in this population.

      • Chronic pruritus in the elderly ; its prevalence, clinical characteristics and associated life habits

        ( Hyunju Jin ),( Min-young Park ),( Kyungnam Bae ),( Sung-min Park ),( Hyun-joo Lee ),( Hyang-suk You ),( Woo-haing Shim ),( Gun-wook Kim ),( Hoon-soo Kim ),( Hyun-chang Ko ),( Moon-bum Kim ),( Byung- 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.2

        Background: Pruritus is one of the most common skin complaint in the elderly. Its prevalence is increasing with the rapid growth of their population. Its prevalence and clinical characteristics were not yet fully elucidated in Korean elderly population. Objectives: To analyze the prevalence, clinical characteristics and their associated life habits for chronic pruritus in Korean elderly. Methods: A face-to-face questionnaire was given to 648 subjects over age of sixty from October to February in 2013 to 2017. All subjects were divided into two groups based on whether they were suffered from chronic pruritus or not. Results: The prevalence of chronic pruritus in the elderly was 72.2% (n=468). In 63.2 percent of the itchy group, itch appeared on a daily basis. During winter (56.1%) and at night (87.4%), itch became worse. Itch was perceived as pricking (30.3%), stinging (18.8%) and burning (11.1%) rather than stabbing (9.8%) and pinching (6.2%). Among daily life habits, proportion in using emollients in itchy group was lower than in non-itchy group with statistical significance (p<0.001). Also, more subjects in itchy group scrubbed and did not use soap (p<0.001) during bath or shower. Conclusion: Pruritus in elderly is not rare. This study highlights the detailed characteristics of itch in Korean elderly. In order to reduce the prevalence of pruritus in elderly, it is better to use soap and emollients and not scrub during bath or shower.

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