조혈모세포이식 이후 발생한 UL97 유전자 597-600 해독틀내 결실이 있는 Ganciclovir 내성 거대세포바이러스 대장염 1예

설창안,고영진,김성한,김미나,성홍섭,이제환 대한임상미생물학회 2015 Annals of clinical microbiology Vol.18 No.2

Human cytomegalovirus (CMV) infection has been a major concern in hematopoietic stem cell transplant recipients. Ganciclovir (GCV) resistance results mostly from mutations within the protein kinase UL97 gene. The three hot spots for GCV resistance (codons 460, 520, and 590-607) were well known. We describe a case of GCV-resistant CMV colitis caused by a 597-600 deletion in UL97 after haplo-identical peripheral blood stem cell transplantation (h-PBSCT) in a 46 year-old man with myelodysplastic syndrome. On post-PBSCT day 28, CMV antigenemia turned positive. Treatment of GCV was started and continued for 12 weeks but CMV antigenemia did not respond to the treatment and CMV colitis was worsened. The UL97 showed the in-frame deletion between codons 597 and 600 by direct sequencing. The treatment was switched to foscarnet and the antigenemia test was consecutively negative twice, and clinical symptoms improved. Despite the recovery of the patient from CMV colitis, the patient expired post-PBSCT day 146 from acute liver failure, hepatorenal syndrome and septic shock. This case is a first report of a deletion 597-600 in CMV UL97 in Korea. A 597-600 deletion in UL97 was responsible for the GCV resistance while preserving susceptibility to foscarnet. (Ann Clin Microbiol 2015;18:-67)

선천성 이상의 염색체마이크로어레이 검사 지침(I): 일반 및 산전검사 지침

설창안,하정숙,원동주,김인숙 대한진단검사의학회 2023 Laboratory Medicine Online Vol.13 No.3

Chromosomal microarray (CMA) testing can enhance the quality of clinical care for congenital abnormalities, including prenatal diagnosis. Laboratories require a comprehensive understanding of the strengths, weaknesses, and purposes of CMA testing. They should also have appropriate plans, guidelines, and documented records for platform validation and quality control at all stages of testing. Performing prenatal CMA testing necessitates understanding the features of prenatal specimens, devising a verification process, reporting results, and providing genetic counseling. This guideline aims to establish standard test protocols for conducting CMA tests, ensuring accurate results, and aiding in diagnosing and treating patients. 염색체마이크로어레이 검사의 활용으로 산전진단을 포함한 선천성 이상에서 임상 진료의 질이 향상될 수 있다. 검사실은 염색체마이크로어레이 검사의 장단점과 목적을 잘 이해해야 하고, 검사의 도입, 변경, 수행 과정에서 플랫폼 검증 및 검사 모든 과정의 질관리에 대한 적절한 계획과 지침 및 문서화된 기록을 가지고 있어야 한다. 산전 CMA 검사는 산전검체의 특성을 이해하고, 거기에 부합하는 검증과정, 결과보고, 포괄적 유전상담에 대한 계획이 필요하다. 본 지침은 국내 CMA 검사 수행의 표준 검사 지침을 마련하고, 검사의 오류를 줄여 정확한 검사 및 해석을 제공함으로써 환자의 진단과 치료에 도움이 되고자 한다.

The First Korean Case of Disseminated Mycetoma Caused by Nocardia pseudobrasiliensis in a Patient on Long-Term Corticosteroid Therapy for the Treatment of Microscopic Polyangiitis

설창안,성흥섭,김덕희,지미숙,정용필,김미나 대한진단검사의학회 2013 Annals of Laboratory Medicine Vol.33 No.3

Nocardia pseudobrasiliensis is predominantly associated with invasive infections in immunocompromised patients. We report a case of disseminated mycetoma caused by N. pseudobrasiliensis in a 57-yr-old woman with microscopic polyangiitis, who was treated for 3 months with corticosteroids. The same organism was isolated from mycetoma cultures on the patient’s scalp, right arm, and right leg. The phenotypic characteristics of the isolate were consistent with both Nocardia brasiliensis and N. pseudobrasiliensis, i.e., catalase and urease positivity, hydrolysis of esculin, gelatin, casein, hypoxanthine, and tyrosine,but no hydrolysis of xanthine. The isolate was identified as N. pseudobrasiliensis based on 16S rRNA and hsp65 gene sequencing. The patient was treated for 5 days with intravenous ampicillin/sulbactam, at which time both the mycetomas and fever had subsided and discharged on amoxicillin/clavulanate. This case highlights a very rare presentation of mainly cutaneous mycetoma caused by N. pseudobrasiliensis. This is the first reported case of N. pseudobrasiliensis infection in Korea.

가속도 부하 환경과 저압 저산소 환경의 쥐의 간에 대한 효과

설창안 ( Seol Chang Ahn ),정수영 ( Chung Soo Young ),설진곤 ( Seol Jin Gon ) 국군의무사령부 2010 대한군진의학학술지 Vol.41 No.1

Objectives: Extreme environments, such as hypergravity and hypobaric hypoxia may alter the homeostasis of the liver. We tried to find out if there are some kinds of injuries in the rat liver after the exposure to the chronic intermittent hypobaric hypoxia and/or hypergravity. Methods : We used male Sprague-Dawley rats, which were divided into 4 groups of C, G, H and G+H. Group C was the control group, and group G was exposed only to the hypergravity of 10 G for 10 minutes daily. Group H was exposed only to the hypobaric hypoxia of altitude of 25,000 feet for 1 hour daily. Group G+H was first exposed to the hypergravity and was next exposed to the hypobaric hypoxia daily. The exposure to the extreme conditions was continued for 15 days. After the exposure we checked liver function tests and did the pathologic analysis of the liver. Results: Serum AST and ALT levels in group H and G+H were lower than in group C. Serum total protein (TP) and albumin levels in group G and G+H were higher than in group C. In the pathologic analysis of liver, we found centrilobular necrosis in group G, H and G+H and hyperplastic change of bile ducts in group H and G+H. Conclusions: Chronic intermittent hypobaric hypoxia decreased serum AST and ALT levels and chronic intermittent hypergravity increased serum TP and albumin levels in the rat. The sequence of the pathologic significance may be group C << G < H < G+H.

POEMS Syndrome: Bone Marrow, Laboratory, and Clinical Findings in 24 Korean Patients

심효은,설창안,박찬정,조영욱,서을주,이정희,윤덕현,서철원,박상혁,장성수 대한진단검사의학회 2019 Annals of Laboratory Medicine Vol.39 No.6

POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.

선천성 이상의 염색체마이크로어레이 검사 지침(II): 보고 및 해석 지침

원동주,설창안,하정숙,김인숙 대한진단검사의학회 2023 Laboratory Medicine Online Vol.13 No.3

Chromosomal microarray (CMA) analysis can enhance the quality of clinical care for congenital abnormalities, including prenatal diagnosis. Laboratories must develop a comprehensive understanding of the strengths, weaknesses, and purposes of CMA analysis. Following the part I, which covers general and prenatal practical CMA guidelines for constitutional abnormalities, this part II provides instructions for CMA reporting and interpretation for the constitutional abnormalities. This guideline is primarily designed to address copy number variants (CNVs) interpretation and result reporting, as well as the preparation of result documents. 염색체마이크로어레이(Chromosomal Microarray, CMA) 검사의 활용으로 산전진단을 포함한 선천성 이상에서 임상 진료의 질이 향상될 수 있다. 검사실은 염색체마이크로어레이 검사의 장단점과 목적을 잘 이해해야 하고, 검사의 도입, 변경, 수행 과정에서 플랫폼 검증 및 검사 모든 과정의 질관리에 대한 적절한 계획과 지침 및 문서화된 기록을 가지고 있어야 한다. 해당 part II 지침은 선천성 이상에 대한 일반 및 산전 CMA의 실용 지침을 다루는 part I에 이어, CMA의 결과 보고와 해석에 대한 지침을 제공한다. 이번 지침에서는 복제수변이(copy number variant, CNV)의 변이 해석 및 결과 해석, 결과지 작성에 대한 내용을 소개하고자 한다.

P-11 : 농 검체에서 분리된 Nocardia pseudobrasiliensis 1예

박숙자,설창안,김덕희,윤남섭,성흥섭,김미나 대한임상병리사협회 2012 임상미생물검사학회 발표자료집 Vol.2012 No.-

배경: Nocardia는 aerobic actinomycetes 중 사람 감염을 일으키는 가장 흔한 원인균으로 면역억제 환자에서 피부 감염, 폐 감염을 주로 일으킨다. Nocardia brasiliensis는 외상으로 인한 피부감염의 흔한 원인으로 알려져 있다. Nocardia pseudobrasiliensis는 이전에 N. brasiliensis로 분류되었으나 adenine을 가수분해하고, 주로 침습성 감염을 일으키는 특징 등으로 N. brasiliensis sensu stricto와는 분리되어 새롭게 명명된 균종이다. 저자들은 농 검체에서 N. pseudobrasiliensis 를 분리하였기에 환자의 병력과 함께 보고하고자 한다. 증례: 결체조직 질환으로 corticosteroid 치료를 받고 있는 57세 여자가 2주 전부터 발생한 발열과 두피, 오른쪽 팔과 다리, 복부에 생긴 다발성 mycetoma를 주소로 내원하였다. 조직 검체 3개의 그람염색에서 호중구가 많이 관찰되었고, 세균은 관찰되지 않았다. 혈액한천배지에서 미세하고 하얀 집락이 자랐으며, SDA 배지에서는 이틀 후 더 크고 불규칙하며 집락의 중앙 부분이 주름지고 하얀 과립이 덮힌 오렌지색 집락이 관찰되었다. 그람염색상은 분지하며 염주모양의 그람양성 간균이었으며, 항산성염색은 음성, modified AFB 염색은 양성이었다. Catalase와 urease는 모두 양성이었다. API® Coryne와 API®20C AUX (BioMerieux, Marcy l``Etoile, France)에서 esculin 양성, gelatin hydrolysis 양성, nitrate 환원 음성이이었고, glucose, glycerol, galactose, N-acetyl-D-glucosamine, inositol and trehalose 양성이었다. Casein, hypoxanthine과 tyrosin 가수분해 양성이었고, xanthine 가수분해는 음성이었다. 16S rRNA 유전자 염기순서 분석 결과 N. pseuodobrasiliensis ATCC 51512T와 99.5% (1,312 bp/1,305 bp) 일치하였으며, Nocardia otitidiscaviarum DSM 43242T와는 98.3% 일치하였다. hsp65 유전자 염기순서 분석에서 N. pseudobrasiliensis DSM 44290T와 99.5% 일치하여 N. pseudobrasiliensis로 동정하였다. Sensititre® Rapid Growing Mycobacteria Plate Format (TREK diagnostic systems, USA)로 감수성 검사를 시행한 MIC (g/mL)는 trimethoprime/sulfamethoxazole 8/152, cefoxitin>128, doxycycline 16, imipenem 64, amoxicillin/clavulanate 32/16, minocycline>8으로 내성이었고, ciprofloxacin ≤0.12, moxifloxacin ≤0.25, amikacin 4, tigecycline 4, clarithromycin 0.25,linezolid ≤1, cefepime 16, ceftriaxone 8, tobramycin ≤1로 감수성이었다. 고찰: 본 증례는 한국에서 처음으로 관찰된 N. pseudobrasiliensis 감염 증례이다. 파종성 감염이 의심되는 환자의 피부 병변에서 분리된 Nocardia species의 생화학적 반응이 N. brasiliensis와 유사할 경우 16S rRNA 유전자 분석을 통해 N. pseudobrasiliensis를 감별해야 할 것으로 판단된다.

The Role of Neuronal Nitric Oxide Synthase on Hypobaric Hypoxiainduced Antinociception in Writhing Test

최승민,중수영,설창안,설진곤,권민수 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.7

It has been reported that hypobaric hypoxia exposure by high altitude is responsible for neuropsychological impairment. In the present study, we examined an effect of hypobaric hypoxia on the writhing test. The ICR mice were exposed in hypobaric chamber with several altitudes (5000, 10,000 or 20,000 ft) for 1 or 2 h, and then immediately injected intraperitoneally (i.p.) with 1% acetic acid for writhing test. Our results show that both 10,000 ft and 20,000 ft exposure induce antinociceptive effect in writhing test, but 5,000 ft does not. In addition, this antinociceptive effect was abolished by L-NAME (nitric oxide synthase inhibitor) pre-treated intraperitoneally, but not naloxone (non-specific opioid receptor antagonist). Furthermore, we examined that neuronal NOS immunoreactivities in the hypothalamus (paraventricular nucleus and arcuate nucleus) were increased by hypobaric hypoxic exposure (10,000ft). These results suggest that hypobaric hypoxic-induced antinociception may be associated with neuronal NOS IR in the hypothalamus.

Langer–Giedion Syndrome with 8q23.1–q24.13 Deletion by Complex Three-way Translocation

민성희,서을주,설창안,김구환,이범희,이동현 대한진단검사의학회 2018 Laboratory Medicine Online Vol.8 No.1

Langer–Giedion syndrome is a very rare genetic disorder that is caused by the deletion on chromosome 8q24.1, encompassing the TRPS1 and EXT1 genes. We describe a 5-month-old female patient who was admitted to our hospital with clinodactyly and weakness in both thumbs. The patient’s karyotype was 46,XX,der(4)t(4;19)(q27;q11),der(8)t(4;8)(q27;q22.3),der(19)t(8;19)(q22.3;q11)del(8)(q23q24.1). Multiplex ligation-dependent probe amplification (MLPA) analysis showed that the patient had a heterozygous deletion, rsa 8q24(P064)x1 and rsa 8q24(P245)x1. Array comparative genomic hybridization (CGH) analysis further revealed three interstitial deletions spanning a total of 13.7 Mb at 8q23.1–q24.13. Based on clinical findings and confirmation by cytogenetic, MLPA, and array CGH analyses, the patient was diagnosed with sporadic Langer–Giedion syndrome with three-way translocations. This is the first case of Langer–Giedion syndrome with complex chromosomal rearrangements in Korea.

부계 완간역위에서 유래한 11pter 중복과 11qter 결실로 발생한 Beckwith-Wiedemann 증후군과 Jacobsen 증후군 1예

최원규,임성은,김구환,이범희,설창안,서을주 대한진단검사의학회 2020 Laboratory Medicine Online Vol.10 No.3

We report a case of Beckwith-Wiedemann syndrome (BWS) and Jacobsen syndrome (JBS) due to 11pter trisomy and 11qter monosomy caused by paternal inv(11)(p15.1q24.2). The patient was born premature and had a variety of clinical features including characteristic facial dysmorphism, cardiac abnormalities, and thrombocytopenia. The karyotype was described as 46,XX,rec(11)dup(11p)inv(11)(p15.1q24.2)pat and methylation-specific multiplex ligation-dependent probe amplification analysis showed duplication of the 11p15.5 region and hypermethylation of imprinting center 1. Chromosomal microarray analysis demonstrated 23.8 Mb duplication on 11pter-p14.3 and 13.8 Mb deletion on 11q23.3-qter. These results were consistent with BWS and JBS, respectively. Because uniparental disomy inherited from paternal pericentric inversion results in simultaneous 11p15.5 duplication and 11q23.3 deletion, appropriate genetic tests are necessary for accurate genetic diagnosis of patients. 저자들은 아버지의 inv(11)(p15.1q24.2)로 기인한 11pter 삼염색체(trisomy)와 11qter 단일염색체(monosomy)로 인해 Beckwith-Wiedemann 증후군(BWS)과 Jacobsen 증후군(JBS)을 함께 가진 환아를 보고하고자 한다. 본 환아는 미숙아로 태어나 안면 이형, 심장기형, 혈소판감소증을 비롯한 다양한 임상 증상을 가지고 있었다. 염색체검사에서 핵형이 46,XX,rec(11)dup(11p)inv(11)(p15. 1q24.2)pat이었으며 메틸화 특이-multiplex ligation-dependent probe amplication 검사에서 11p15.5 부위의 중복과 imprinting center 1의 과메틸화를 확인했다. 염색체 마이크로어레이검사에서 11pter-p14.3의 23.8 Mb의 중복과 11q23.3-qter의 13.8 Mb의 결실을 확인하여 각각 BWS와 JBS를 진단할 수 있었다. 부계의 완간역위에서 유래한 uniparental disomy로 인해 11p15.5 부위의 중복과 11q23.3 부위의 결실이 동시에 생길 수 있기 때문에, 환자의 정확한 유전학적 진단을 위해 염색체검사와 더불어 MLPA, 마이크로어레이검사 등과 같은 유전학적 검사가 필요하다.