가와사끼병에서 Matrix metalloproteinase 9과 Tissue inhibitor of metalloproteinase 1, 2의 임상적 중요성

윤기욱,윤신원,이정주,채수안,임인석,최응상,유병훈,이미경,Yun, Ki-Wook,Yun, Sin-Weon,Lee, Jung-Ju,Chae, Soo-Ahn,Lim, In-Seok,Choi, Eung-Sang,Yoo, Byoung-Hoon,Lee, Mi-Kyung 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.4

목 적: 가와사끼병은 급성 전신성 미세혈관염으로서, 소아의 후천성 심질환의 가장 흔한 원인이다. 가와사끼병의 관상동맥병변에 대한 조직병리학적 소견은 미만성 혈관염에 의한 관상동맥벽의 파괴를 시사하는데, matrix metalloproteinase (MMP)와 그 내인성 억제인자인 tissue inhibitor of metalloproteinases (TIMP)가 이러한 과정에 주요한 역할을 할 것으로 생각되고 있으며, 그 중에도 MMP-9이 최근 가장 주목을 받고 있다. 따라서 본 연구에서는, 한국의 가와사끼병 환아들에서 MMP-9과 그 억제인자들인 TIMP-1, TIMP-2가 갖는 임상적 중요성을 평가하고자 하였다. 방 법: 가와사끼병 환아 47명을 연구대상으로 하였고, 급성열성 세균감염 환아 14명을 대조군으로 하였다. 혈중 MMP-9, TIMP-1, TIMP-2의 농도를 kit를 통한 효소 면역법을 이용하여 측정하였고, 각 임상 단계 및 관상동맥병변의 유무에 따라 비교분석하였다. 결 과: 급성기에 MMP-9과 TIMP-1은 가와사끼군에서 대조군에 비해 유의하게 높았고, TIMP-2는 오히려 낮았다($P$<0.05). 급성기에 증가한 MMP-9은 아급성기와 회복기에 유의하게 감소하였다($P$<0.05). 관상동맥 확장군과 비확장군의 비교에서는, 확장군에서 급성기 MMP-9과 TIMP-1, MMP-9/TIMP-2가 낮았으며, 아급성기로 가면서 통계적으로 유의하게 증가하였다가 다시 회복기로 가면서 감소하는 양상을 보였다($P$<0.05). MMP-9은 급성기와 아급성기에 TIMP-1과 통계적으로 유의한 양의 상관관계를 보였고, TIMP-2와는 아급성기와 회복기에 음의 상관관계를 보였다($P$<0.05). 결 론: 이러한 결과들은 MMP-9과 TIMP-1의 증가, 그리고 MMP-9과 TIMP-2의 불균형이 가와사끼병, 특히 그 관상동맥병변의 병태생리에 핵심적인 역할을 한다는 사실을 시사한다 하겠다. 더 종합적이고 심도 깊은 연구를 위해서 좀 더 많은 대상자를 포함하는 큰 규모의 연구들이 향후 이루어져야 할 것이다. Purpose : Kawasaki disease (KD) is a systemic vasculitis, a leading cause of pediatric acquired heart disease. Histopathological findings of coronary artery lesion (CAL) in KD indicate destruction of the coronary artery wall with diffuse vasculitis. Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) might play central roles in this process. Special attention to MMP-9 has recently been emerging. This study was performed to investigate the clinical significance of MMP-9 and its inhibitors, TIMP-1 and TIMP-2, in KD. Methods : We compared 47 KD patients with 14 febrile controls. Serum MMP-9 and TIMP-1, TIMP-2 were measured by ELISA and compared according to clinical stages and coronary involvement. Results : In acute stage, MMP-9 and TIMP-1 were significantly higher, whereas TIMP-2 was lower, in KD than those in febrile controls ($P$<0.05). The elevated MMP-9 levels in acute phase significantly decreased during the subacute and convalescent phases ($P$<0.05). During acute phase, the MMP-9, TIMP-1, and MMP-9/TIMP-2 levels in the CAL group were lower than those in the non-CAL group, but they increased significantly in the subacute phase ($P$<0.05). MMP-9 has a positive correlation with TIMP-1 in the acute and subacute phases, and negative correlation with TIMP-2 in the subacute and convalescent phases ($P$<0.05). Conclusion : These results suggest that MMP-9, TIMP-1, and the imbalance in MMP-9 and TIMP-2 might play important roles on the pathophysiology of KD and especially on the development of CAL. However, further larger studies are needed.

Uropathogenic Escherichia coli ST131 in urinary tract infections in children

윤기욱,이미경,김원용,임인석 대한소아청소년과학회 2017 Clinical and Experimental Pediatrics (CEP) Vol.60 No.7

Purpose: Escherichia coli sequence type (ST) 131, a multidrug-resistant clone causing extraintestinal infections, has rapidly become prevalent worldwide. However, the epidemiological and clinical features of pediatric infections are poorly understood. We aimed to explore the characteristics of ST131 Escherichia coli isolated from Korean children with urinary tract infections. Methods: We examined 114 uropathogenic E. coli (UPEC) isolates from children hospitalized at Chung-Ang University Hospital between 2011 and 2014. Bacterial strains were classified into STs by partial sequencing of seven housekeeping genes (adk, fumC, gyrB, icd, mdh, purA, and recA). Clinical characteristics and antimicrobial susceptibility were compared between ST131 and non-ST131 UPEC isolates. Results: Sixteen UPEC isolates (14.0%) were extended-spectrum β-lactamase (ESBL)-producers; 50.0% of ESBL-producers were ST131 isolates. Of all the isolates tested, 13.2% (15 of 114) were classified as ST131. There were no statistically significant associations between ST131 and age, sex, or clinical characteristics, including fever, white blood cell counts in urine and serum, C-reactive protein, radiologic abnormalities, and clinical outcome. However, ST131 isolates showed significantly lower rates of susceptibility to cefazolin (26.7%), cefotaxime (40.0%), cefepime (40.0%), and ciprofloxacin (53.3%) than non-ST131 isolates (65.7%, 91.9%, 92.9%, and 87.9%, respectively; P<0.001 for all). ESBL was more frequently produced in ST131 (53.3%) than in non-ST131 (8.1%) isolates (P<0.01). Conclusion: ST131 E. coli isolates were prevalent uropathogens in children at a single medical center in Korea between 2011 and 2014. Although ST131 isolates showed higher rates of antimicrobial resistance, clinical presentation and outcomes of patients were similar to those of patients infected with non-ST131 isolates.

최근 5년간(2007-2011) 단일 대학병원의 소아 환자에서 발생한 의료관련감염의 원인균 분포

윤기욱,이미경,윤신원,채수안,임인석,최응상,유병훈 대한의료관련감염관리학회 2012 의료관련감염관리 Vol.17 No.1

배경: 병원감염은 모든 입원환자들에 있어서 가장 중요한 의료 사안 중 하나이며, 입원 기간의 연장 및 부수적인 의료 비용의 증가는 물론 해당 환자의 이환율과 사망률을 높이는 원인이다. 적절한 감염 관리를 위해서는 해당 지역 사회 및 병원의 역학적 자료의 활용이 필수적이나, 병원감염에 대한 국내 소아 자료는 미미한 실정이다. 방법: 2007년 1월부터 2011년 12월까지 총 5년 간 중앙대학교병원에 입원하였던 18세 미만의 소아들에서 발생하였던 병원감염 중 원인미생물이 확인된 증례들에 대하여 후향적 분석을 수행하였다. 각 병상별, 연도별 병원감염률을 조사하였고, 병원감염의 종류 및 원인미생물의 분포를 확인하였다. 원인미생물의 항생제 감수성 양상을 분석하여 다제내성균의 검출 현황을 확인하였고 국내외 역학 자료들과 비교 분석하였다. 결과: 연구기간 동안 총 122명의 환아에서 181건의 병원감염이 있었다. 해당 기간 동안 1,000 재원일수 당 발생한 병원감염은 2.4건이었으며, 이 중 UTI가 53건(29.3%)으로 가장 많았고, 다음 이 폐렴이었다(33건, 18.2%). Staphylococcus aureus가 총 50건으로 전체 원인미생물 중에서 26.2%를 차지하여 소아 병원감염증의 가장 흔한 원인균이었고, 이 중 42건(84%)이 methicillin-resistant S. aureus로 확인되었다. 그람음성균 중에는 Escherichia coli가 가장 흔하였다. ESBL은 52.9%의 발현율을 보였으며 Acinetobacter baumannii와 Pseudomonas aeruginosa의 imipenem에 대한 내성률은 각각 58.8%와 55.0%로 확인되었다. 결론: 중앙대학교병원에서 지난 5년간 소아에서 발생한 병원감염 중 요로감염이 가장 흔하였고 균종으로는 MRSA가 가장 흔히 동정되었다. 소아에서도 병원감염을 적절히 관리하기 위하여 더 적극적이고 다각적인 감염 관리 및 다제내성균의 확산 방지를 위한 조치가 이루어져야 할 것이다. 아울러 지역 사회 및 각 병원의 지속적인 역학 자료 수립 또한 필요하리라 생각된다.

Evaluation and Management of Neonates with Possible Congenital Zika Virus Infection

윤기욱 대한신생아학회 2017 Neonatal medicine Vol.24 No.3

Zika virus infection is, typically, either asymptomatic or causes mild illness; however, it may present severe clinical manifestations in neonates. Zika virus can be transmitted from a pregnant woman to her fetus, subsequently causing microcephaly and serious brain anomalies. Recently, the full spectrum of anomalies in neonates congenitally infected by Zika virus has been delineated as congenital Zika syndrome. Five major features are unique to congenital Zika syndrome: severe microcephaly with a partially collapsed skull, thin cerebral cortices with subcortical calcifications, macular scarring and focal pigment mottling of the retina, congenital contractures, and extrapyramidal symptoms. Recognition of this phenotype in neonates and infants by clinicians can help ensure appropriate etiologic evaluation of Zika virus infection and determine the required duration of follow-up and clinical care. Neonates with congenital Zika virus infection should be evaluated by a team of multiple specialists within the first year of life; the evaluations should include assessments of vision, hearing, feeding, growth, and neurodevelopmental function. Moreover, it is recommended that infants who show laboratory evidence of congenital Zika virus infection without apparent abnormalities be continuously monitored and screened by the primary care provider; repeated hearing tests should be carried out for such infants.

고막 체온계와 이마 체온계의 정확성 및 유용성에 대한 연구

윤기욱,임인석 대한소아청소년과학회 2005 Clinical and Experimental Pediatrics (CEP) Vol.48 No.8

Purpose : The presence and degree of fever in children is a useful indicator of illness. This project aimed to assess the accuracy and usefulness of infrared tympanic membrane(TM) & forehead feverscan thermometers for measuring children's temperatures. Methods : Data were obtained from 1,050 children with a median age of 4.5 years. They visited the pediatric clinics at Chung-Ang University Yongsan Hospital from January 2004 to December 2004. We measured body temperatures at axilla by mercury thermometer, at ear by infrared TM thermometer and at forehead by feverscan. Then we analyzed the correlation between these data. Results : Mercury and TM thermometer, and Mercury and forehead feverscan thermometer very well correlated with each others(P<0.05). And the sensitivity of infrared TM thermometer(right and left) to correctly identify febrile children was 81.1 percent and 82.4 percent, the positive predictive value to detect a fever was 81.8 percent and 73.6 percent. The sensitivity of forehead feverscan was 83.3 percent and the positive predictive value was 74.4 percent. Conclusion : The tympanic membrane temperature measured by the BRAUN IRT 3020Ⓡ and forehead arterial temperature measured by the HubDIC DOTORYⓇ feverscan accurately reflects mercury axillary temperature, validly assesses the presence of fever in children, and is easy to use. The Braun IRT 3020Ⓡ & HubDIC DOTORYⓇ therefore is an adequate tool to assess fever and may be used both in a clinical setting and for research purposes. 목 적 : 감염과 질병상태의 유용한 인자인 열의 존재와 정도를 좀더 손쉽고 정확하게 확인하기 위해, 고막체온계 및 이마체온계의 정확성과 유용성을 평가하고자 하였다. 방 법 : 2004년 1월 1일부터 12월 31일 까지 중앙대학교 부속병원에 입원하여 치료받았던 환아 중 무작위로 1,050명을 선출하여 대상으로 하였으며, 수은 체온계, 고막 체온계(BRAUN IRT 3020 ) 및 이마 체온계(HubDIC DOTORY )로 동시에 체온을 측정하였고 이를 비교, 분석하여 상관관계를 조사하였다.결 과 : 고막 체온계와 이마 체온계의 측정치는 각각 표준 검사인 수은 체온계의 측정치와 유의한 상관관계 및 상호 교환성을 가졌으며, 양측 고막 간, 그리고 고막 체온계와 이마 체온계 사이에서도 유의한 상관관계를 보였다. 발열에 대한 고막 체온계의 민감도는 오른쪽과 왼쪽에서 각각 81.1%, 82.4%였고, 양성 예측률은 각각 81.8%, 73.6%였다. 이마 체온계의 민감도는 83.3 %였으며, 양성 예측률은 74.4%였다.결 론:고막 체온계(BRAUN IRT 3020Ⓡ) 및 이마형 체온계(HubDIC DOTORYⓇ)가 액와형 수은체온계와 통계적으로 유의한 상관성 및 일치성을 보이며(P<0.05), 또한 발열에 대한 민감도 및 양성 예측률이 매우 높아 일상의 가정에서나 병원에서 진료목적으로, 연구 목적으로 체온 측정하는 데 유용하게 사용될 수 있을 것으로 본다.

The First Case of X-linked Alpha-thalassemia/Mental Retardation (ATR-X) Syndrome in Korea

윤기욱,채수안,이정주,윤신원,유병훈,임인석,최응상,이미경 대한의학회 2011 Journal of Korean medical science Vol.26 No.1

Mutation of the ATRX gene leads to X-linked alpha-thalassemia/mental retardation (ATR-X)syndrome and several other X-linked mental retardation syndromes. We report the first case of ATR-X syndrome documented here in Korea. A 32-month-old boy came in with irritability and fever. He showed dysmorphic features, mental retardation and epilepsy, so ATR-X syndrome was considered. Hemoglobin H inclusions in red blood cells supported the diagnosis and genetic studies confirmed it. Mutation analysis for our patient showed a point mutation of thymine to cytosine on the 9th exon in the ATRX gene, indicating that Trp(C), the 220th amino acid, was replaced by Ser(R). Furthermore, we investigated the same mutation in family members, and his mother and two sisters were found to be carriers.

Molecular typing of uropathogenic Escherichia coli isolated from Korean children with urinary tract infection

윤기욱,김도수,김원용,임인석 대한소아청소년과학회 2015 Clinical and Experimental Pediatrics (CEP) Vol.28 No.1

Purpose: We investigated the molecular types of uropathogenic Escherichia coli (UPEC) by using conventional phylogrouping, multilocus sequence typing (MLST), and fimH genotyping. Methods: Samples of patients younger than 18 years of age were collected from the Chung-Ang University Hospital over 2 years. Conventional phylogenetic grouping for UPEC strains was performed by polymerase chain reaction (PCR). Bacterial strain sequence types (STs) were classified on the basis of the results of partial sequencing of seven housekeeping genes. In addition, we analyzed nucleotide variations in a 424-base pair fragment of fimH , a major virulence factor in UPEC. Results: Sixty-four UPEC isolates were analyzed in this study. Phylogenetic grouping revealed that group B2 was the most common type (n=54, 84%). We identified 16 distinctive STs using MLST. The most common STs were ST95 (35.9%), ST73 (15.6%), ST131 (12.5%), ST69 (7.8%), and ST14 (6.3%). Fourteen fimH allele types were identified, of which 11 had been previously reported, and the remaining three were identified in this study. f1 (n=28, 45.2%) was found to be the most common allele type, followed by f6 and f9 (n=7, 11.3% each). Comparative analysis of the results from the three different molecular typing techniques revealed that both MLST and fimH typing generated more discriminatory UPEC types than did PCR-based phylogrouping. Conclusion: We characterized UPEC molecular types isolated from Korean children by MLST and fimH genotyping. fimH genotyping might serve as a useful molecular test for large epidemiologic studies of UPEC isolates.

Streptococcus pneumoniae Type Determination by Multiplex Polymerase Chain Reaction

윤기욱,조은영,홍기배,최은화,이환종 대한의학회 2011 Journal of Korean medical science Vol.26 No.8

The purpose of this study was to develop pneumococcal typing by multiplex PCR and compare it with conventional serotyping by quellung reaction. Pneumococcal strains used in this study included 77 isolates from clinical specimens collected from children at Seoul National University Children’s Hospital from 2006 to 2010. These strains were selected as they represented 26 different serotypes previously determined by quellung reaction. Molecular type was determined by 8 sequential multiplex PCR assays. Bacterial DNA extracted from cultured colonies was used as a template for PCR, and primers used in this study were based on cps operon sequences. Types 6A, 6B, 6C, and 6D were assigned based on the presence of wciNβ and/or wciP genes in 2 simplex PCRs and sequencing. All 77isolates were successfully typed by multiplex PCR assays. Determined types were as follows:1, 3, 4, 5, 6A, 6B, 6C, 6D, 7C, 7F, 9V, 10A, 11A, 12F, 13, 14, 15A, 15B/15C, 19A, 19F,20, 22F, 23A, 23F, 34, 35B, and 37. The results according to the PCR assays were in complete concordance with those determined by conventional quellung reaction. The multiplex PCR assay is highly reliable and potentially reduces reliance upon conventional serotyping.

저산소 모델에 따른 간장 기능 손상에 관한 연구

윤기욱 ( Ki Wook Yoon ),이상호 ( Sang Ho Lee ),이선미 ( Sun Mee Lee ) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.2

지카바이러스 감염: 소아감염 전문가로서의 관점

윤기욱 ( Ki Wook Yun ) 대한소아감염학회 2016 Pediatric Infection and Vaccine Vol.23 No.1

The Zika virus, a flavivirus related to dengue and Japanese encephalitis was discovered in the Zika forest in Uganda, 1947. Since Zika virus was first reported in Brazil in May 2015, infections have occurred in at least 40 countries, especially in the Americas. Zika virus infection usually is asymptomatic or causes mild illness, but may be related to severe clinical manifestations, particularly microcephaly and Guillain-Barre synd rome. Although the possibility of autochthonous Zika virus transmission in South Korea is low, the imported cases and Zika virus-transm itting mosquito should be adequately monitored and promptly managed. In addition, enhancing preparedness for Zika virus infection are needed.