중합효소연쇄 반응법에 의한 인형거대세포바이러스(human cytomegalovirus)의 신속한 검출

김의종,오명돈,박기호,신형식,이환종,김남중,최강원 대한감염학회 1996 감염 Vol.28 No.4

목 적 : 인형거대세포바이러스(HCMV)는 면역 저하 환자에서 폐렴, 망막염, 간염 등 치명적인 감염증의 원인이다. 전통적인 세포 배양법으로 HCMV를 분리하기까지는 1주에서 4주가 걸리므로 이 바이러스에 의한 질환이 의심되는 경우 신속한 진단법을 이용한 진단이 바람직하다. 저자들은 한국에서 분리되는 야생주 HCMV를 검출하는데 중합효소 연쇄 반응법을 이용할 경우의 진단적 유용성을 알기 위하여, 전통적인 세포배양법으로 HCMV가 분리된 검체를 이용하여 중합효소 연쇄 반응법의 특이도와 민감도를 평가하였다. 방 법 : 국내 야생주 HCMV 15주, 그리고 전통적인 바이러스 배양법으로 HCMV가 분리된 소변 15검체를 대상으로 중합효소 연쇄 반응을 실시하였다. 중합효소 연쇄 반응은 Towne주의 immediate early antigen의 유전자에서 유리된 primer MIE와 AD169주의 immediate early antigen의 유전자에서 유리된 primer IE를 이용하였다. 증폭 산물은 겔 전기영동 후 EtBR으로 염색하여 자외선 하에서 관찰하였다. Primer IE에 의한 증폭산물은 또한, DNA blot hybridization 방법으로 확인하였다. 결 과 : 1) 국내 HCMV 야생주 15주를 대상으로 중합효소 연쇄 반응을 한 결과 primer IE를 이용한 경우에는 100%(15/15)에서 177bp의 증폭 산물이 관찰되었고, 이들 증폭 산물은 모두 probe IE와 보합 결합되었다. primer MIE를 이용한 경우에는 93%(14/15)에서 435bp의 증폭 산물이 관찰되었다. 2) 세포 배양법으로 HCMV가 분리된 소변 15검체를 대상으로 primer IE를 이용하여 중합효소 연쇄 반응을 한 결과 direct gel analysis 법으로는 73%(11/15)에서, 보합 결합법으로는 87%(13/15)에서 관찰되었다. Primer MIE를 이용한 경우에는 direct gel analysis법으로 87%(13/15)에서 435bp의 증폭 산물이 검출되었다. 결 론 : Primer IE와 MIE를 이용한 중합효소 연쇄 반응법은 국내 야생주 HCMV를 신속히 검출하는데 유용한 검사법이다. Background : Human cytomegalovirus(HCMV) can cause pneumonitis, hepatitis, retinitis and other serious diseases in the immunocompromised patients. It takes 1 to 4 weeks to diagnose HCMV infection by conventional virus culture. Therefore, when HCMV diseases are suspected, a rapid diagnostic method such as polymerase chain reaction(PCR), antigen assay or shell vial culture is desirable. We evaluate the sensitivity and specificity of a PCR for the rapid detection of HCMV wild strains in Korea. Methods : We used 2 sets of primers ; primer IE and primer MIE derived from the sequence for immediate early gene of AD169 strain and Towne strain, respectively. Fifteen clinical isolates of HCMV, suspended in MRC-5 cells, were amplified by PCR. Fifteen urine specimens which were positive for HCMV by conventional virus culture were also amplified. Amplification products were analyzed by polyacrylamide gel electrophoresis. The products from PCR with primer IE were also identified by DNA blot hybridization. Results : PCR using primer IE gave the PCR products in all of the 15 HCMV wild strains. All of these were hybridized with probe IE. When primer MIE were used, 93%(14/15) of the wild strains showed amplified bands by direct gel analysis. When the urine specimens were amplified by PCR with primer IE, amplified bands were seen in 73%(11/15) by direct gel analysis ; 87%(13/15) by hybridization method. When primer MIE were used, 87%(13/15) of the urine specimens showed the PCR products by direct gel analysis. Conclusion : Polymerase chain reaction with primer IE and MIE may be a specific and sensitive diagnostic method for rapid detection of HCMV wild strains in Korea.

Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation

Kim, Seong-Ryeol,Song, Jae-Hyoung,Ahn, Jae-Hee,Lee, Geun-Shik,Ahn, Huijeong,Yoon, Sung-il,Kang, Seung Goo,Kim, Pyeung-Hyeun,Jeon, Sang-Min,Choi, Eun-Ji,Shin, Sooyoung,Cha, Younggil,Cho, Sungchan,Kim, Elsevier 2018 Antiviral research Vol.151 No.-

<P>Human rhinovirus (HRV) infection causes more than 80% of all common colds and is associated with severe complications in patients with asthma and chronic obstructive pulmonary disease. To identify antiviral drug against HRV infection, we screened 800 FDA-approved drugs and found budesonide as one of the possible drug candidates. Budesonide is a corticosteroid, which is commonly used to prevent exacerbation of asthma and symptoms of common cold. Budesonide specifically protects host cells from cytotoxicity following HRV infection, which depend on the expression of glucocorticoid receptor. Intranasal administration of budesonide lowered the pulmonary HRV load and the levels of IL-1 beta cytokine leading to decreased lung inflammation. Budesonide regulates IL-1 beta production following HRV infection independent of inflammasome activation. Instead, budesonide induces mitochondrial reactive oxygen species followed by activation of autophagy. Further, the inhibition of autophagy following chloroquine or bafilomycin Al treatment reduced the anti-viral effect of budesonide against HRV, suggesting that the antiviral activity of budesonide was mediated via autophagy. The results suggest that budesonide represents a promising antiviral and anti-inflammatory drug candidate for the treatment of human rhinovirus infection.</P>

A novel nicotinoyl peptide, nicotinoyl-LVH, for collagen synthesis enhancement in skin cells

( Hyoung Shik Kim ),( Seung Hwan Ryu ),( Hye In Kim ),( Seung Hee Cho ),( Jeong Hun Lee ),( Byung Suk Han ),( Kyung Rok Lee ),( Sang Hyun Moh ) 한국응용생명화학회 2016 Journal of Applied Biological Chemistry (J. Appl. Vol.59 No.3

A novel Nicotinoyl fused peptide, Nicotinoyl-LVH, was synthesized by solid phase peptide synthesis method, purified, and tested in cultured skin cells. Nicotinoyl-LVH enhanced the expression level of collagen mRNA and its fragments in fibroblasts. These data show that this novel Nicotinoyl peptide is a promising biomaterial in the anti-aging functional cosmetic market.

Glycosyltransferase - a specific marker for the discrimination of Bacillus anthracis from the Bacillus cereus group

Kim, Wonyong,Kim, Ji-Yeon,Cho, Sung-Lim,Nam, Sun-Woo,Shin, Jong-Wook,Kim, Yang-Soo,Shin, Hyoung-Shik Microbiology Society 2008 Journal of medical microbiology Vol.57 No.3

<P>Bacillus anthracis, the aetiological agent of anthrax, has been taxonomically classified with the Bacillus cereus group, which comprises B. cereus, Bacillus thuringiensis, Bacillus mycoides, Bacillus pseudomycoides and Bacillus weihenstephanensis. Although the pathogenesis and ecological manifestations may be different, B. anthracis shares a high degree of DNA sequence similarity with its group member species. As a result, the discrimination of B. anthracis from its close relatives in the B. cereus group is still quite difficult. Suppression subtractive hybridization (SSH) was performed to search for genomic differences between a B. anthracis Korean isolate CR and the most closely related B. cereus type strain KCTC 3624(T). Two-hundred and five B. anthracis CR clones obtained by SSH underwent Southern hybridization, and comparative sequences were analysed using the blast program from the National Center for Biotechnology Information (NCBI). Subsequently, primer sets based on the glycosyltransferase group 1 family protein gene specific to B. anthracis were designed from the sequences of subtracted clones, and their specificities were evaluated using eight B. anthracis, 33 B. cereus, 10 B. thuringiensis, six B. mycoides, one B. pseudomycoides, one B. weihenstephanensis and 19 strains from 11 other representative Bacillus species. PCR primers specific for the glycosyltransferase group 1 family protein gene did not amplify the desired products from any of the Bacillus strains under examination, except B. anthracis alone. These findings may be useful in the future development of efficient diagnostic tools for the rapid identification of B. anthracis from other members of the B. cereus group.</P>

Isolation and Biological Characterization of Transforming Growth Factor-β and Bone-Forming Protein from Mineralized Tissues

Kim, Gwan-Shik,Kim, Se-Won,Kim, Jong-Yeo,Ko, Sun-Il,Kim, Hyoung-Ryoung,Kim, Myung-Soo,Ko, Seong-Hee,Cheong, Dong-Kyun The Official Publication of Korean Academy of Oral 1994 International Journal of Oral Biology Vol.18 No.2

Extracellular matrix of mineralized tissue is known to contain a number of growth and differentiation factors. Substantial evidences indicated that these polypeptide factors may have physiologic significance in the normal growth, maintenance and regeneration of bone, but their biological functions are still confusing. In the present study, we have extracted transforming growth factor-β(TGF-β) and putative osteoinductive proteins from several mineralized tissues. Presence of TGF-β in all bone tissues examined and dentin was detectable by immunoblot analysis and soft agar assay with NRK cells. And bone cells in developmental stage, such as fetal rat calvarial cells, actively produce TGF-β reflectong that it is an autocrine and paracrine factor involved in regulation of bone metabolism. SDS-PAGE profile of extracts indicated that protein fractions with the same Mr of known osteoinductive factors have been isolated. By subcutaneous implantation of purified TGF-β or solubilized matrix proteins in rats after reconstitution with carrier, deposition exhibiting new bone-like appearance or histologic changes associated with new bone formation was observed. These results suggest that TGF-β and matrix proteins may play an important roles in the local regulation of bone formation and possibly of odontogenesis. And this study also supports the hypothesis that TGF-β is an osteoinductive growth factor in vivo.

Tetrahydrobiopterin Regulates Cardiac Mitochondrial Function

KIM Hyoung Kyu,JEON Juhyun,PARK Won Sun,HA Seung Hee,CHOI Seong Woo,KIM Nari,KIM Sanguk,PARK Young Shik,HAN Jin 大韓藥學會 2009 大韓藥學會 總會 및 學術大會 Vol.2009 No.2

A Study on the Adverse Events of the Yellow Fever Vaccine at an International Travelers' Clinic

Kim, Tae Hee,Lee, Jae Yo,Park, Hyang Mi,Kim, Seung Soo,Shin, Hey Jung,Bang, Ji Hwan,Shin Hyoung Shik,Kim, Jae Yoon 대한감염학회 2009 감염과 화학요법 Vol.41 No.3

Background : Yellow fever (YF) can be prevented through vaccination, but YF vaccination causes adverse events. The increasing number of travelers to YF-endemic areas prompted an investigation of YF vaccination's adverse events-on Koreans. Materials and Methods : From January to December 2007, 318 live-17DD vaccinees at the International Travelers' Clinic of the National Medical Center were enrolled in this study. Results : The adverse events were evaluated through six telephone interviews of 309 subjects (male: 168, 54.4%) on days 3, 6, 9, 16, 23, and 30 after the administration of the vaccine. There were 106 adverse events in 97 (31.4%) subjects aged 11 months to 70 years (male: 56, 18.1%). Of the 34 (11.0%) subjects who had underlying diseases, 3 (1.0%) reported adverse events (P=0.06). Nineteen (6.1%) of the 72 (23.3%) subjects who concurrently received other vaccines also experienced adverse events (P=0.29). Those who had underlying illnesses and those aged 10 to 19 years reported more frequent adverse events (P=0.06 and 0.14, respectively) but the significance of this finding is uncertain. Most of the adverse events occurred within 10 days after the vaccination and spontaneously subsided. Conclusion : This study shows that most of the YF vaccine's adverse events are well tolerated and that the vaccine safely protects a vaccinee from YF.

Lidocaine, Thrombin, Epinephrine 의 항균효과

김진우,이동건,전혜선,김승준,김석찬,안중현,김치홍,권순석,김영균,김관형,문화식,신완식,송정섭,박성학 대한감염학회 2005 감염과 화학요법 Vol.37 No.6

목적 : 기관지내시경 검사에서 흔히 사용되는 국소마취제인 lidocaine과 내시경시 지혈목적으로 사용되는 thrombin과 epinephrine이 각종 균주에 미치는 항균효과에 대해 알아보고자 하였다. 재료 및 방법 : 균주는 가톨릭대학교 성모병원에서 2004년 3월부터 2004년 9월까지 임상검체 에서 동정된 S. aureus, S. pneumoniae, K. pneumoniae, P. aeruginosa 각각 42, 42, 42, 43주를 대상으로 하였다. Lidocaine, thrombin, epinephrine 감수성 검사는 National Committee for Clinical Laboratory Standards (NCCLS, 2002)의 기준에 따랐다. 결과 : Lidocaine은 S. aureus, S. pneumoniae, P. aeruginosa에서 MIC_(50), MIC_(90) 모두 20,000 ㎍/mL 이었다. K. pneumoniae는 각각 10,000 ㎍/mL이었다. Thrombin은 S. aureus와 P. aeruginosa에서 MIC50 500 lU/mL 과 MIC_(90) 500 IU/mL 이상이었고, K. pneumoniae에서는 MIC_(50)과 MIC_(90)이 모두 500 lU/mL이상이었으나 S. pneumoniae에서는 MIC_(50)과 MIC_(90)은 125 IU/mL이었다. Epinephrine은 K. pneumoniae, S. pneumoniae에 대한 MIC_(50), MIC_(90)가 모두 >500 ㎍/mL이었고, S. aureus와 P. aeruginosa에 대한 MIC_(50), MIC_(90)가 모두 500 ㎍/mL이었다. 결론 : 기관지 내시경 검사에서 흔히 쓰이는 lidocaine, thrombin, epinephrine 등의 약제들이 호흡기 질환의 흔한 병원균인 S. aureus, S. pneumoniae, K. pneumoniae, P. aeruginosa 균주들에 대해 항균 효과가 있을 수 있어 세균배양검사에 영향을 미칠 수 있겠다. Background : We performed this stody to find out about antimicrobial effect of lidocaine which is commonly used local anesthetic, and thrombin and epinephrine used for hemostasis during bronchoscopic procedures. Materials and Methods : The microorganisms that were cultured from specimens obtained during bronchoscopy were Staphylococcus aureus (n=42), Streptococcus pneumoniae (n=42), Klebsiella pneumoniae (n=42), and Pseudomonas aeruginosa (n=43) collected from St. Mary's Hospital, from March to Sep 2004 were used for susceptibity testing. Susceptibility to lidocaine, thrombin, and epinephrine were tested according to the National Committee for Clinical Laboratory Standards. Result : MIC_(50) and MIC_(90) of lidocaine for S. aureus, S. pneumoniae, P. aeruginosa were all 20,000 ㎍/mL and that for K. pneumoniae were 10,000 ㎍/mL. MIC_(50) and MIC_(90) of thrombin for both S. aureus and P. aeruginosa was 500 IU/mL and above 500 IU/mL, respectively; that for K. pneumoniae were all above 500 IU/mL and for S. pneumoniae they were 125 IU/mL, MIC_(50) and MIC_(90) of epinephrine for K. pneumoniae and S. pneumoniae were above 500 ㎍/mL; that for S. aureus and P. aeruginosa were 500 ㎍/mL. Conclusion : We observed possible antimicrobial effect of lidocaine, thrombin, and epinephrine in vitro against pathogens such as S. aureus, S. pneumoniae, K. pneumoniae, P. aeruginosa, which are common respiratory microorganisms. The use of these agants could affect the result of bacterial culture.

Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

Kim, Wan-Su,Choi, Woo Jin,Lee, Sunwoo,Kim, Woo Joong,Lee, Dong Chae,Sohn, Uy Dong,Shin, Hyoung-Shik,Kim, Wonyong The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.1

The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and proinflammatory cytokine ($IL-1{\beta}$, IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, ($91.0{\pm}3.2%$), similar to ${\alpha}$-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases.

A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center

Kim Seyoung,Kim Jeong Ah,Park Hyesook,Park Sohee,Oh Sanghoon,Jung Seung Eun,Shin Hyoung-Shik,Lee Jong Koo,Han Hee Chul,Woo Jun Hee,Park Byung-Joo,Choi Nam-Kyong,Kim Dong-Hyun 대한의학회 2024 Journal of Korean medical science Vol.39 No.26

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024. This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels—high, moderate, limited, or insufficient—while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as “convincingly supports” (“evidence established” in the 2024 NASEM report), “favors acceptance,” “favors rejection,” or “inadequate to accept or reject.” The CoVaSC has established an independent committee to conduct causality assessments using the weightof-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-ofevidence framework and to detail the considerations involved in its practical application in the CoVaSC.