연구논문 : 만성 바이러스간질환에서 간섬유화의 다양한 비침습 혈청표지자검사의 비교

김선민 ( Sun Min Kim ),손주현 ( Joo Hyun Sohn ),김태엽 ( Tae Yeob Kim ),노영욱 ( Young Wook Roh ),은창수 ( Chang Soo Eun ),전용철 ( Yong Cheol Jeon ),한동수 ( Dong Soo Han ),오영하 ( Young Ha Oh ) 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.4

목적: 만성 바이러스간질환에서 병의 경과와 예후를 평가하고 치료반응을 예측함에 있어 간섬유화의 진단은 중요하다. 최근 간섬유화 평가에 표준방법이지만 침습적 간생검을 대신하여 여러 가지 비침습적 진단법이 이용되고 있고, 또한 새로운 검사법들이 개발되고 있다. 저자들은 만성 B형 및 C형간염 환자를 대상으로 임상에서 광범위하게 흔히 시행하는 혈액검사와 임상 소견을 이용한 아래와 같은 진단법들만으로 간섬유화를 얼마나 정확하게 평가할 수 있는지 알아보고, 단일 검사로 간섬유화를 평가하는 데 유용하다고 알려져 있는 hyaluronic acid(HA)와 IV형 콜라겐 농도와 비교하여 그 임상적 유용성을 평가하였다. 대상과 방법: 2002년 3월부터 2007년 2월까지 만성 바이러스간 질환으로 간생검을 시행받은 225명의 환자(HBV 180명, HCV 43명, HBV+HCV 2명)를 대상으로 분석하였다. 간생검을 시행하는 날에 말초혈액검사, 혈액응고검사, 혈청생화학검사를 시행하고, 혈중 HA, IV형 콜라겐 농도를 측정하였다. 간섬유화의 정도는 F0(섬유화가 없음), F1(문맥역 섬유화), F2(문맥주변부 섬유화), F3(섬유성 격막) 및 F4(간경변증)의 4단계로 구분하였다. 대상 환자를 F0-1, F2-4 혹은 F0-2, F3-4의 두 집단으로 분류하여 두 집단을 구분하고자 할 때 AAR(AST/ALT ratio), API(age-platelet index), APRI(AST to platelet index), CDS(cirrhosis discriminant score), platelet count, HA, IV형 콜라겐의 예측능을 area under the receiver operating characteristic curve (AUROC)값을 이용하여 비교하였다. 결과: 대상환자의 섬유화의 단계는 F0 집단은 17명, F1 집단은 40명, F2 집단은 61명, F3 집단은 74명, F4 집단은 33명이었다. 의미 있는 간섬유화를 F2 이상으로 판단할 때, 의미 있는 섬유화의 예측에 대한 AUROC 값은 APRI=0.822, CDS=0.776, platelet count=0.773, API=0.756, HA=0.749, IV형 콜라겐=0.718, AAR=0.642 순이었고, F3 이상의 광범위한 섬유화 예측에 대한 AUROC값은 CDS=0.835, platelet count=0.795, API=0.794, HA=0.766, AAR=0.711, IV형 콜라겐=0.697, APRI=0.691 순으로 관찰되었다. 결론: 만성 바이러스간질환에서 간섬유화를 평가하는 데 임상 소견 및 혈액검사를 이용한 방법들이 비침습적 진단법 중 단독 검사로도 유용한 것으로 알려져 있는 혈중 HA와 IV형 콜라겐 농도와 비교하여 우월하거나 대등하였다. 특히 APRI는 다른 인자들에 비해 F2 이상의 의미 있는 섬유화를 예측하는 데 가장 유용하였고, CDS는 F3 이상의 광범위한 섬유화를 예측하는 데 가장 유용하였다. Background/Aims: The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. Methods: We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. Results: There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (≥F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (≥F3). Conclusions: Conclusions: All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis. (Korean J Hepatol 2009;15:454-463)

항정신병약물 사용 중인 정신분열병 환자에서 올란자판으로의 교체 방법에 관한 연구(II) : Comparison of Safety 안전성 비교

안용민,권용실,권준수,민성호,박두병,양문정,소형석,송종호,신윤식,우행원,유범희,이홍석,정한용,한창환,김용식 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.5

연구목적: 이 다기관 공동임상연구는 사용 중인 항정신병약물을 ’직접 교체 방법’또는 ’시작-감량 교체 방법’중 한 가지 방법으로 올란자핀으로 교체한 후, 안정성 측면에서 두 교체 방법 간의 비교와 교체후의 변화를 관찰하기 위한 것이다. 방법: 국내 13개 병원의 입원 및 외래에 내원한 환자들 중 ICD-10 지단기준으로 정신분열병에 해당되며, 임상적으로 항정신병약물 교체가 필요한 환자를 대상으로 하였다. 두 가지 교체 방법 중 한 가지를 무작위로 피험자에 적용하였으며, ’직접 교체 방법’에 배정된 경우에는 사용중인 항정신병약물을 일시에 중단하고 10㎎의 올란자핀을 바로 투여하였고, ’시작-감량 교체 방법’에 배정된 경우는 10㎎의 올란자핀 투여하고 2주에 걸쳐서 기존 약물을 감량하여 중단하였다. 올란자핀 사용기간은 총 6주이며, 용량은 5∼20㎎ 범위로 제한하였다. 한정성 평가를 위해서 체중, 생명징후, 자발적인 이상반응 복, 실험실 검사 그리고 Simpson-Angus Scale(SAS), Barnes akathisia rating scale(BARS), Abnormal involuntary movement scale(AIMS). Liverpool University neuroleptic side effect rating scale(LUNSERS)등을 이용하였다. 결과: 총 103명의 정신분열병 환자를 대상으로 하였다. 사용한 올란자핀의 용량, 벤조디아제핀의 병용률, 탈락률과 탈락 사유, 자발적인 이상반응 보고, 생명징후, 실험실 검사 그리고 대부분의 부작용 척도 상에서 임상적으로 의미 있는 차이를 두 교체 방법간에 발견하지 못하였다. 다만 AIMS의 감소는 ’직접 교체 방법’군에서 보다 적었고, 항콜린제의 병용률은 ’시작-감량 교체 방법’군에서 보다 많았다. 기저 상태에서 전체 피험자의 SAS와 BARS 점수는 각각 3.5점과 1.8점이었으며 70% 이상의 피험자가 고프로락틴 혈증을 보였다. 올란자핀으로 교체한 후, SAS, BARS, AIMS 점수의 유의한 감소가 있었으며 고프로락틴 혈증을 보인 피험자 분율도 약 30%이하로 감소하였다. 그러나 교체 방법과 상관없이 올란자핀 교체 후 유의한 체중 증가가 있었다. 결론: 이 연구를 통해 교체 방법에 관계없이 비교적 안전하고 용이하게 올란자핀으로 교체 할 수 있음을 알 수 있었다. 그리고 기존 항정신병약물을 올란자핀으로 교체함으로써 일부 부작용들을 줄일 수 있음을 간접적으로 관찰할 수 있었다. 하지만 이 연구는 여러 제한점과 문제점을 지니고 있기 때문에 보다 체계적인 연구를 통해 검정이 필요하리라 생각된다. Objectives: This multicenter clinical trial involving 13 hospital sites compared the safely of switching to olanzapine between ’direct switching method’ and ’start-tapering switching method’. Method: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For ’direct switching method’group, previous antipsychotics were abruptly discontinued and 10㎎ of olanzapine was administered, and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20㎎. The safety of switching to olanzapine was measured with vital sings including body weight, adverse events reported spontaneously, laboratory tests, and various scales such as Simpson-Angus Scale(SAS), Barnes Akathisia Rating Scale(BARS). Abnormal Involuntary Movement Scale(AIMS), and Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS). Results: 103 patients were switched to olanzapine in this study. The comparison between two switching methods did not show any significant difference in the dosage of olanzapine used, the concomitant use of benzodiazepine, the rate and reasons of drop-out, the adverse events, vital signs, laboratory tests, and most scales for measuring side-effects. However, the decrease in AIMS scores was significantly lower in ’direct switching method’ group, and the concomitant use of anticholinergics was comparatively greater in ’start-tapering switching method’ group. At baseline, SAS and BARS scores were 3.5 and 1.8 points respectively, and more than 70% of the subjects showed hyperprolactinemia. After switching to olanzapine, SAS, BARS, and AIMS scores were significantly decreased and the proportion of the patients with hyperprolactinemia was also decreased to less than 30%. However significant weight gain after the treatment of olanzapine was observed regardless of switching method. Conclusion: This study may suggest that switching to olanzapine can be done with relatively high safety regardless of switching methods and olanzapine can significantly decrease some side-effects induced by other antipsychotics.

Genome-wide investigation of a Korean synthetic breed, Woori-Heukdon using the Illumina PorcineSNP60K BeadChip

Yong‑Min Kim,Ha‑Seung Seong,Jung‑Jae Lee,Da‑Hye Son,Jin‑Su Kim,Soo‑Jin Sa,Young‑Sin Kim,Tae‑Jeong Choi,Kyu‑Ho Cho,Joon‑Ki Hong,Jung‑Woo Choi,Eun‑Seok Cho 한국유전학회 2020 Genes & Genomics Vol.42 No.12

Background: Woori-Heukdon (KWH) is a Korean synthetic pig breed generated using Chookjin-Duroc (KCD), Chookjin-Chamdon (KCC), and their crossbreds. Currently, there is a severe lack of studies investigating the Korean breed populations including wild boars (KWB) throughout the genome. Objective: This study was performed to investigate the genetic characteristics of Korean pig populations at the genome-wide level. Methods: Using the SNP dataset derived from genotyped and downloaded datasets using the Illumina PorcineSNP60K BeadChip, we compared the genomes of 532 individuals derived from 23 pig breeds to assess the genetic diversity, inbreeding coefficient, genetic differentiation, and population structure. Results: KWB showed the lowest average expected heterozygosity (HE = 0.1904), while KWH showed the highest genetic diversity (HE = 0.02859) among Korean populations. We verified that the genetic composition of KWH, showing USD of 74.8% and KCC of 25.2% in ADMIXTURE analysis. In population structure analyses, KCC was consistently shown to be separated from other pig populations. In addition, we observed gene flow from Western pigs to a part of Chinese populations. Conclusion: This study showed that Korean native pigs, KCC have genetic differences in comparison with Chinese and Western pigs; despite some historical records and recent genetic studies, we could not find any clear evidence that KCC was significantly influenced by Chinese or Western breeds in this study. We also verified the theoretical genomic composition of KWH at the molecular level in structure analyses. To our knowledge, this is the first genomic study to investigate the genomic characteristics of KWH and KCC.

분산 실시간 시스템을 위한 로컬 스케줄러 확장에 관한 연구

하수철,최용락,박진섭 大田大學校 1988 論文集 Vol.7 No.1

This paper is a study on the scheduling mechanism for distributed real time systems. A MINIX system uses preemptive priority scheduling policy and round robin method which take multi-level queueing systems. but this method is unsuitable for distributed real time systems, because it is designed for single syytem environments and used fixed priority based on cpu time. This paper presents extended scheduling mechanism of MINIX system for distributed real time system environment. First, Decision Routine is designed for determination of the execution of the real time processes on the local node. Second. Local Scheduler and Global Scheduler are designed for lical scheduling and global scheduling of real time process based deadline and computation time. Designed module is implimented on MINIX system under IBM-PC/AT.

磁氣 Bubble間의 磁氣學的 Energy의 算出에 關한 硏究

河龍守 중앙대학교 기술과학연구소 1981 기술과학연구소 논문집 Vol.8 No.-

Provided we can calculate the interaction between two bubbles in different sheets determined thickness we will be able to find out the knowledge that the ratio of thickness of two sheets, the separation between the sheets, and the magnetizations of the sheets, etc. influence the interaction between two bubbles in different sheets. The diameters of two bubbles are based upon different sheets determined thickness and a magnetic field so that stability founds and the minimum diameters of two bubbles be found out, therefore this paper has made clear the result of the calculation indicated the basic interaction.

복어의 건조와 냉동에 의한 근육조직의 변화

하수용,하진환,송대진 濟州大學校 工科大學 産業技術硏究所 1991 産業技術硏究報告 Vol.2 No.-

The observations on the histological changes of muscular tissue during the processes, such as drying, freezing and thawing were carried out to get basic data for processes and storage of puffer, Fugu xanthopterus. The results are as follows : Epidermal part is tough and thick. That is connected with muscular tissue by soft and tough connective tissue . The muscular tissue structures of puffer are epidermis, corium and partially dark muscle, without hypodermic fat. According to the respective muscular parts, there exist crossed muscle fibers like abalone. The connective tissues of intercellular materials and myocommata were found abundantly. During the couresc of drying, the dehydration of muscular tissue occured on connective tissue in the early stage ; thus caused widening between muscle bundles respectively. In the late stage of drying, contraction of myocommata and the widening between muscle bundles were appeared. After frozen storage for a month, distributions of ice crystal were affected deeply by freezing temperature, that is. those were observed mainly on the intracellular sites when frozen at -35℃. while on the extracellular sites when frozen at -10℃. but the ice crystals formed in both temperatures caused the condensation of muscle fibers. Thawing fter frozen storage for a month, a recovery of muscle fibers and figuration were observed in muscular tissue stored at -35℃, while insufficien recovery of muscle fibers and disfiguration by dehydration at -10℃. In the observation of uscle figbers when the tissue was homogenated with 1% cold formali. the fresh tissue was fragmented to myofibril level and intermixed like thred, while the frozen tissue for a month became rigid due to disfiguration, contraction, the loss of elasticity and water holding capacity.

半導體의 熱電的性質의 考察

河龍守 釜山工業大學校 1969 論文集 Vol.9 No.-

T subset定量을 위한 抗牛赤血球 IgG抗體의 分離·精製

夏潤文,李振鏞,林壽德 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 1981 東西醫學硏究所 論文集 Vol.1 No.1

사람에 있어서 免疫담당세포의 하나인 T 細胞는 몇몇 subpooulation으로 나누어지고 있으며, 그중 ?? 및 ??를 同定하는 수단으로 사용되는 牛赤血球抗體중에서 우선 純粹 IgG抗體를 分離, 精裂하였으며, 이 精裂된 IgG抗體는 標準製品과의 比較實驗에서 ?? 細胞의 一致되는 成積을 얻을 수 있었다. Antisera to ox red blood cell were prepared by intraperitioneal hypermultiple injections without adjuvant in outbred white rabits. Purified IgG fraction from these rabbits anti-ox red blood cell antiserum for T subset assay was obtained by precipitation with 50% saturated ammonium sulphate followed by DEAE-cellulose chromatography and Sephadex G-150 gel filtration. These purified IgG fraction was compared with Cappel company standard IgG fraction for ?? subpopulation assay. We used home-made IgG fraction and obtained favorable results in ?? subpopulation assay as Cappel company standard IgG fraction.

복어의 乾燥와 冷凍에 依한 筋肉組織의 變化

하수용,송대진,하진환 濟州大學校工科大學附屬産業技術硏究所 1991 尖端技術硏究所論文集 Vol.2 No.-

복어의 加工貯藏을 위한 基礎資料를 얻고자 乾燥, 冷凍, 解凍過程中의 筋育組織變化를 觀察하여 다음과 같은 結果를 얻었다. 1. 복어의 筋育組織構造는 表皮, 眞皮 부분에 따라 약간의 血合肉層과 普通肉으로 構成되어 있고 皮下脂肪層이 없으며, 細胞間質, 筋隔膜등의 結締組織은 비교적 많은 편이었다. 2. 筋肉組織은 질기고 두꺼운 表皮層과 질기고 부드러운 結締組織으로 연결되어 있으며, 筋肉의 部分에 따라 전복처럼 서로 교차하는 筋纖維가 存在하였다. 3. 乾燥에 依한 組織의 變化는 乾燥初期에는 結締組織의 脫水收縮이 일어나고 相對的으로 筋束의 間隔은 벌어지며, 乾燥末期에는 筋隔膜, 筋節은 收縮하고 筋束사이는 벌어지며 筋細胞는 密集되는 現象을 나타내었다. 4. 1개월 凍結貯藏後의 氷結晶의 分布는 貯藏溫度에 따라 달랐으며 -35℃에서는 細胞內에, -10℃에서는 細胞外에 氷結晶이 생겼고 筋纖維의 凝集現象을 볼 수 있었다. 5. 1개월 凍結貯藏後 解凍한 경우 -35℃의 것에서는 거의 生鮮狀態로 復元되었으나 -10℃의 것은 脫水變形이 심하여 復元이 不充分하였고, -35℃ 凍結後 -20℃에서 3個月동안 貯藏하였던 것은 氷結晶의 흔적이 그대로 남아있고 脫水收縮이 심하며 復元狀態도 극히 不良하였다. 6. 筋肉의 均質化에서 생것은 실처럼 가늘게 으깨어지고 풀어지며, 1개월간 凍結貯藏한 것은 풀어지지 않았다. 그리고 凍結貯藏溫度의 차이에 따른 變化는 거의 볼 수 없었고, 凍結貯藏에 依해 保水性과 彈力이 低下함에 따라 收縮變形이 일어나며 단단해졌다. The observations on the histological changes of muscular tissue during the processes, such as drying, freezing and thawing were carried out to get basic data for processes and storage of puffer, Fugu χanthopterus. The results are as follows: Epidermal part is tough and thick. That is connected with muscular tissue by soft and tough connective tissue. The muscular tissue structures of puffer are epidermis, corium and partially dark muscle, without hypodermic fat. According to the respective muscular parts, there exist crossed muscle fibers like abalone. The connective tissues of intercellular materials and myocommata were found abundantly. During the courese of drying, the dehydration of muscular tissue occured on connective tissue in the early stage; thus caused widening between muscle bundles respectively. In the late stage of drying, contraction of myocommata and the widening between muscle bundles were appeared. After frozen storage for a month, distributions of ice crystal were affected deeply by freezing temperature, that is, those were observed mainly on the intracellular sites when frozen at -35℃, while on the extracellular sites when frozen at -10℃, but the ice crystals formed in both temperatures caused the condensation of muscle fibers. Thawing after frozen storage for a month, a recovery of muscle fibers and figuration were observed in muscular tissue stored at -35℃, while insufficient recovery of muscle fibers and disfiguration by dehydration at -10℃. In the observation of muscle fibers when the tissue was homogenated with 1% cold formalin, the fresh tissue was fragmented to myofibril level and intermixed like thread, while the frozen tissue for a month became rigid due to disfiguration, contraction, the loss of elasticity and water holding capacity.

어떤 흰쥐 뇌에서 부신절제가 전기경련 충격에 의한 조기유전자 발현에 미치는 영향

하규섭,강웅구,정희연,주연호,조수철,박주배,김용식 大韓神經精神醫學會 1996 신경정신의학 Vol.35 No.4

부신피질 호르몬이 70g 이내의 어린 흰쥐의 뇌에서 전기경련 충격에 의한 조기유전자(IEG)의 발현에 미치는 급성 효과 및 만성 효과를 살펴보기 위하여 본 연구를 수행하였다. 70g 이내의 생식선이 발달하지 않은 수컷 Sprague-Dawley 흰쥐에서 양측 부신을 절제한지 3일과 14일 후에 전기경련 충격으로 경련을 유발시켜 대뇌 피질과 해마에서 c-fos, jun B, TIS 1 의 발현 양상을 관찰하고 이를 대조군과 비교하여 다음과 같은 결과를 얻었다. 1) 부신절제 후 대뇌 피질에서 전기경련 충격에 의한 c-fos와 jun B mRNA 발현은 일찍 최대치에 도달하고 일찍 감소하는 경향을 보였으며, 초기의 발현이 강화되는 경향을 보였다. 이러한 경향은 jun B가 c-fos 보다 뚜렷하였으며, 부신절제 후 3일이 경과된 경우보다 14일이 경과된 경우가 뚜렷하였다. 2) TIS 1의 경우에는 대뇌 피질에서 이러한 초기 발현의 강화가 관찰되지 않았으며, 부신절제 14일된 어린 흰쥐에서만 발현이 억제되는 경향을 보였다. 3) 부신절제는 해마에서는 전기경련 충격에 의한 c-fos와 jun B의 발현에 영향을 미치지 않았다. 부신절제 3일 후 전기경련 충격에 의한 TIS 1의 발현은 억제되는 경향이 관찰되었으나, 부신절제 14일 후에는 이러한 경향이 관찰되지 않았다. 이상의 결과로부터 부신절제는 전기경련 충격에 의한 IEG의 발현에 영향을 미치며, 그 영향은 흰쥐의 뇌의 부위, IEG의 종류에 따라 차이가 있음을 알수 있었고, 흰쥐의 연령 및 부신피질 호르몬을 제거한 기간 등의 영향도 있음을 확인할수 있었다. To evaluate the influences of adrenocortical hormone on the signal transduction system in young brain, the authors observed the effects of bilateral adrenalectomy on the induction of immediate early genes(IEGs) such as c-fos, jun B, and TIS 1 by electroconvulsive shock(ECS) in the young rats. The young(70g) male Sprague-Dawley rats were treated with ECS(130V, 0.5sec) at day 3 or 14 after bilateral adrenalectomy. They were sacrificed at 0, 15, 30, 45, and 60 minutes after ECS and cerebral cortex and hippocampus were dissected from their brans . The induction of IEGs were assessed with northern by hybridization. The band intensities of the autoradiographs measured by densitometer were compared between adrenalectomized group and sham-operated control group. In the cerebral cortex, c-fos and jun B appeared and disappeared earlier, and enhanced in the earlier phase of the induction in the adrenalectomized group. These trends were more prominent for jun B than for c-fos, and were more prominent at day 14 than at day 3 after adrenalectomy. The induction of TIS 1 was attenuated at day 14 after adrenalectomy. In the hippocampus, the induction of c-fos and jun B by ECS was not influenced by adrenalectomy. The induction of TIS 1 was attenuated at day 3 after adrenalectomy. These results suggest that adrenalectomy has influences on the induction of IEGs by ECS in rat brain differently, depending on the brain region, the kind of IEGs, the age of the rats, and the time passed after adrenalectomy.