Differential Manifestation of Ocular Phenotypes in TALEN-mediated p19arf Knockout FVB/N and C57BL/6J mouse lines

Jin‑Sung Park,Joo‑Il Kim,Hyun‑Jin Lim,Soo‑Kyung Ryu,Euna Kwon,Kang‑Min Han,Ki‑Taek Nam,Han‑Woong Lee,Byeong‑Cheol Kang 한국유전학회 2020 Genes & Genomics Vol.42 No.9

Background p19arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19arf has been associated with ocular defects, but the mixed background of the knockout (KO) mouse strain used raised a concern on the accuracy of the phenotypes observed in association with the targeted gene due to genetic heterogeneity. Object We carried out a study to investigate into the efect of genetic background on the manifestation of p19arf KO associated phenotypes. Methods We characterized the phenotypes of novel p19arf KO mouse lines generated in FVB/N and C57BL/6J using a transcription activator-like efector nuclease (TALEN) system in comparison to the reported phenotypes of three other p19arf-defcient mouse lines generated using homologous recombination. Results Ninety-fve percent of FVB/N-p19arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19arf KO mice from week 4. Besides these, both strains developed normally from birth to week 26 without increased tumorigenesis except for a subcutaneous tumor found in a C57BL/6J-p19arf KO mouse. Conclusion Our fndings demonstrated surprisingly variable manifestation of p19arf-linked phenotypes between FVB/N and C57BL/6J mice, and furthermore between our mouse lines and the established lines, indicating a critical impact of genetic background on functional study of genes using gene targeting strategies in mice.

The Evolving Policy Debate on Border Closure in Korea

Su-Jin Kang,Jihyun Moon,Heewon Kang,Heekyoung Nam,Sangwoo Tak,Sung-Il Cho 대한예방의학회 2020 Journal of Preventive Medicine and Public Health Vol.53 No.5

302 Copyright © 2020 The Korean Society for Preventive Medicine J Prev Med Public Health 2020;53:302-306 • https://doi.org/10.3961/jpmph.20.213 The Evolving Policy Debate on Border Closure in Korea SuJin Kang1, Jihyun Moon2, Heewon Kang1, Heekyoung Nam3, Sangwoo Tak1, Sung-il Cho1,3 1Institute of Health and Environment, Seoul National University, Seoul, Korea; 2Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Korea; 3Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea Brief Report Objectives: In this paper, we aimed to investigate the evolving debate over border closure in Korea during the coronavirus disease 2019 (COVID-19) pandemic, to address the main themes associated with border closure, and to discuss the factors that need to be considered when making such decisions. Methods: We collated and reviewed previously conducted review studies on border closures during infectious disease outbreaks to derive relevant themes and factors. Results: According to our systematic review on border closures and travel restrictions, the effects of such containment efforts are limited. We suggest considering the following factors when determining whether to impose border closure measures: (1) disease characteristics, (2) timeliness of implementation, (3) transmission delay and the basic reproduction number, (4) globalization and pandemics, and (5) social and economic costs. Conclusions: Our assessment indicates that the effects of border closures are at best temporary and limited. Alternative measures must be contemplated and implemented to suppress the spread of COVID-19 in particular and infectious diseases more broadly.

정신보건관련시설 입원(소)자의 주요 정신장애 유병률 : 전국 20개 시설의 입원(소)자를 대상으로

조성진,조맹제,서동우,함봉진,홍진표,배재남,이준영,이동우,박종익,전홍진,김성주,김용익 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.6

Objectives : One of the objectives of this study is to estimate the prevalence rates of psychiatric diagnoses in the combined populations of psychiatric hospitals, psychiatric nursing facilities and homeless asylums using the Korean version of the Composite International Diagnostic Interview (K-CIDI), which is a comprehensive and fully standardized interview schedule to assess psychiatric disorders for diagnosis. The Other objective is to compare with previously studied prevalence rates of Psy-chiatric diagnoses using the results of this study. Methods : The study subjects, aged from 181o 64 years, were randomly selected from 64,582 institutionalized population of psychiatric hospitals, Psychiatric nursing facilities and homeless asylums as of 30, June, 2001. Twelve trained interviewers administered the K-CIDI to the selected respondents. A total of 1,875 respondents (male 1,194, female 681) completed the interview. Results : The lifetime and one year prevalences of any diagnosis excluding nicotine dependence · withdrawal, anxiety disorder, eating disorder, somatoform disorder were 88.2% (male 88.1%, female 88.3%), and 65.8% (male 62.7%, female 73.7%), respectively. The lifetime and one year prevalences of schizophrenia and other psychotic disorders were 78.5% (male 75.3%, female 83.7%), and 56.8% (male 51.9%, female 64.8%), respectively. The lifetime and one year prevalences of alcohol use disorder (dependence/abuse) were 26.7% (male 37.9%, female 8.3%), and 8.7% (male 12.8%, female 2.1%), respectively. The lifetime and one year prevalences of mood disorder were 18.1% (male 13.5%, female 25.8%), and 10.4% (male 7.2%,female 16.9%), respectively. The lifetime and one year prevalences of schizophrenia and other psychotic disorders were comparable with the 2001 community survey by 1.19% to 1.32%, and 0.51% to 0.61%, respectively. The lifetime and one year prevalences of schizophrenia were also comparable by 0.16% to 0.28%, and 0.16% to 0.25%, respectively. There were no significant changes of prevalence rates when correction were applied to other psychiatric diagnosis. Conclusion : The results of this study could be used for evaluating the distribution of psychiatric diagnoses in mental health related facilities and for planning mental health policies.

하시모토 갑상선염과 동반된 갑상선 유두암에서 BRAFV600E의 발현과 임상적 특징

남성진,최영식,박요한,김정훈 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.2

Background: An association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) is still controversial. Studies to date established the coexistence of HT in 11% to 36% of PTC patients. BRAFV600E mutation was presented 90% with no HT, 64% with HT in PTC patients. Therefore, BRAFV600E mutation is associated with the pathogenesis of PTC arising in HT. The purpose of this study was to identify predictive factors for the coexistence of PTC and HT and to evaluate the association of the BRAFV600E mutation with the clinicopathological features of coexistence of PTC and HT. Methods: A total of 247 patients underwent surgery for thyroid disorders between January 2007 and April 2009. In all, 212 patients was diagnosed as thyroid papillary carcinoma only (PTC group), 33 had coexistence of PTC and HT (PTC+HT group), and 2 had been diagnosed with HT. DNA was extracted from paraffin embedded thyroid tumor specimens taken from 99 patients with PTC, 13 coexistence of PTC and HT, and 2 was HT. The presence of the BRAFV600E mutation was determined by polymerase chain reaction amplification of exon 15 followed by direct sequencing. Results: Among clinicopathological features sex, age, tumor size and capsule invasion was not significant between PTC group and PTC+HT group. Lymph node metastasis and stage was significantly lower in PTC+HT group than PTC group (p=0.044). BRAFV600E mutation was found in 34 of the 99 PTC group (34.3%), 1 of the 13 PTC+HT group and 2 HT show no BRAFV600E mutation. Conclusion: These data demonstrated that the coexistence of PTC and HT was less aggressive than PTC only.

제2형 당뇨병 남성 환자에서 유리 테스토스테론과 성호르몬 결합 글로블린 농도

남기덕,김영설,박철영,오승준,김덕윤,우정택,김성운,양인명,김진우,최영길 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.6

연구배경:인슐린저항성은 제2형 당뇨병과 심혈관질환의 주요한 위험 인자로 성호르몬과 상호 관계가 있다고 알려져 있다. 그러나 여성과는 달리 남성에서는 연령과 인슐린저항성에 따른 유리 테스토스테론과 성호르몬 결합 글로블린 농도의 변화에 대한 연구가 부족한 실정이다. 그러므로, 본 저자등은 제2형 당뇨병 남성 환자에서 정산인과 비교해서 유리 테스토스테론과 성호르몬 결합 글로블린 농도를 측정하고 연령에 따른 변화 정도를 알아보고자 하였다. 방법:대상 환자 모두에서 연령과 체질량지수, 총 콜레스테롤, 중성지방, 공복혈당과 인슐린 농도를 측정하였다. 혈중 유리 테스토스테론 농도는 방사면역측정법(radioimmunoassay)을 이용해서 측정하였고, 혈중 성호르몬 결합글로불린은 면역방사계측측정법(immunoradiometric assay)을 이용해서 측정하였다(Diagnostic System Laoratories, Wbster, TX, USA). 결과:1)제2형 당뇨병 남성 환자에서 정상 대조군 남성에 비해 성호르몬 결합글로불린은 104.1±35.0 vs 25.7±3.5 mole×10??로 의미 있게 높았으나(p<0.001), 유리 테스토스테론은 13.7±9.5 vs 13.6±6.5 ng/dL로 차이가 없었다. 2)연령과 성호르몬 결합 글로블린 사이의 상관 계수는 제2형 당뇨병 남성 환자에서 0.40로 중등고의 양의 상관 관계를 보였고(p<0.001), 정상 대조군 남성에서 0.11로 유의한 상관 관계를 보이지 않았다. 연령과 유리 테스토스테론 사이의 상관 계수는 제2형 당뇨병 남성 환자에서 0.08, 정상 대조군 남성에서-0.17로 모두에서 유의한 상관 관계를 보이지 않았다. 3)연령과 체질량지수를 보정한 후에 제2형 당뇨병 남성 환자와 정상 대조군 남성에서 혈중 인슐린 농도, 유리 테스토스테론과 성호르몬 결합 글로블린 사이에는 상관 관계가 없었다. 결론:제2형 당뇨병 남성 환자에서 정상 남성에 비해 성호르몬 결합 글로블린 농도가 증가되어 있었으며, 유리 테스토스테론은 차이가 없었다. 연령이 증가함에 따라 성호르몬 결합 글로블린이 제2형 당뇨병 남성 환자에서 정상 남성에 비해 증가 폭이 의미있게 컸으며, 유리 테스토스테론은 변화가 없었다. Background: Insulin resistance is a risk factor for cardiovascular disease and type 2 diabetes mellitus. There are many previous studies indicating that insulin lowers serum sex hormone-binding globulin levels, and there is inverse correlation between insulin resistance and serum sex hormone-binding globulin levels in women. However, in men, a limited number of studies are available to explain the effect of sex hormone on age and insulin. Therefore, the present study was undertaken to investigate the relationship among free testosterone, hormone-binding globulin and age in type 2 diabetic men and control subjects. Method: Age, body mass index, total cholesterol, triglyceride, fasting blood sugar, and insulin concentrations were examined on 89 type 2 diabetic men and 47 control subjects. The free testosterone level was measured by commercially available double-antibody system (Radioimmunoassay). The sex hormone-binding globulin level was also measured by commercially available double-antibody system(Immunoradiometric assay). Results: 1) Sex hormone-binding globulin level was significantly increased in patients with type 2 diabetes. However, there was no significantly difference in free testosterone level between the two groups. 2) Sex hormone-binding globulin was positively correlated with age (r=0.4, p <0.001) in patients with type 2 diabetes. Sex hormone-binding globulin and free testosterone were not correlated with age in control sujects. 3) Free testosterone and sex hormone-binding globulin concentrations were not significantly related to serum insulin concentration after adjusting for age and body mass index. Conclusions: We observed increased sex hormone-binding globulin concentration in diabetes man, and was a positively related to age. Further studies are needed to understand the relationships between age, insulin resistance, testosterone, and sex hormone-binding globulin concentrations(J Kor Diabetes Asso 24:699~707,2000).

양식넙치, Paralichthys olivaceus 치어의 스쿠티카충 감염경로

진창남,이창훈,오상필,나오수,허문수 한국어병학회 2003 한국어병학회지 Vol.16 No.1

넙치양식시 피해가 많은 스쿠티카충의 치어기 감염경로를 규명하기 위하여 2001년도에 제주도지역 넙치양식장과 종묘배양장을 대상으로 조사를 실시하였다. 종묘생산 과정에서의 감염경로 조사를 위해 먹이생물인 클로렐라, 알테미아, 로티퍼 배양수조를 조사한 결과 로티퍼 배양수조에서 밑바닥 찌꺼기와 로티퍼 사체 및 생체에서 스쿠티카충 감염이 확인되었다. 스쿠티카충이 감염된 로티퍼를 주어에 투여한 후 자어 사육수조 바닥에는 스쿠티카충이 다량 번식하였다. 넙치 치어에 최초 감염은 부화자어가 착저 완료후 10일경 (부화후 40일경)에 사육수조 바닥에 서식하고 있던 스쿠티카충이 치어에 감염되었다. 스쿠티카충에 감염된 넙치 치어를 조직학적 방법으로 조사하여 감염경로를 확인한 결과, 안구나 뇌에 감염되는 경로는 주둥치 부분이나 등지느러미 앞부분의 표피에 감염된 후 상피조직과 근조직과 신경조직에 따라 뇌로 이행되었다. 그리고 내부장기에 감염되는 경로는 배지느러미나 뒷지느러미 연조막에 침투하여 상피조직과 근조직를 따라 항문과 직장으로 이행되었으며 비뇨생식공을 통해서 요도와 방광, 직장상피세포, 복강, 췌장, 신장외막, 신장 등으로 침투하였다. 스쿠티카충이 감염되지 않은 로티퍼를 이용하는 종묘배양장에서는 먹이생물 배양수조, 자어사육수조, 자어 및 치어 (전장 7㎝ 전후)에서 스쿠티카충이 감염되지 않았다. The infection characteristics with scuticociliates at on-land rearing farms and hatcheries of flounder, Paralithys olivaceus was investigated during they year of 2001 by juvenile infection routes. When culture tanks for living food organisms such as chlorella, rotifer, and Artemia were searched, scuticocilates were detected both in live and dead rotifer, and at the dregs of culture tank bottoms at almost hatcheries. When rotifer infected with scuticocilates fed on fish larvae, lots of scuticocilate were inhabited at the bottom of fry rearing tanks. After feeding on scuticocilates-infected rotifer on fish larvae, first infection was detected at 10 days after bottom dwelling or 40 days old after hatching. By histopathological examination we confirmed the infection route of eyeball of brain contamination was that the ciliate worms digged through mouth and front part of the dosal fin cuticle, transferred into eyeball along the epithelium and muscle tissue, and reached finally into brain by the muscle and nerve tissue. The infection of internal organs was clarified into two routes. The first route was started form the infection at ventral and anal fin rays by the worms, and reached at the anus and rectum through the epithelium and muscle tissue. The second route was initiated from the infection at urinary organ and reached into the rectum epithelium cells, inner wall of intestine, abdominal cavity, pancreas, kidney, and pancreas. At seed production farms where fish larvae fed on scuticocilate-free rotifer, the worms were not detected not only at the food organisms culture tanks and juvenile rearing tanks but also larval flounder less than 7㎝ in total length.

IPS Empress 도재관의 파절강도 : 하악 중절치에서 절단연 삭제량과 측면 경사도에 따른 영향

남영성,김계순,정영찬,김유리,동진근 원광대학교 치의학연구소 2003 圓光齒醫學 Vol.12 No.1

The purpose of this study was to compare the fracture strength of the IPS Empress ceramic crown according to the incisal depth (1.5mm, 2.0mm, 2.5mm) and axial inclination (4˚, 8˚, 12˚) of the lower central ncisor. After 10 metal dies were made for each group, the IPS Empress ceramic crowns were fabricated and each crown was cemented on each metal die with resin cement. The cemented crowns mounted on the testing jig were inclined 30 degrees and a universal testing machine was used to measure the fracture strength. The results of this study were as follows : 1. The fracture strength of the ceramic crown with 2.0mm depth and 12˚ inclination was the highest (648 N). Crowns of 1.5mm depth and 4˚ inclination had the lowest strength (482 N). 2. There were no significant differences of the fracture strength by axial inclination in same incisal depth group. 3. The fracture mode of the crowns was similar. Most of fracture lines began at the loading area and extended through proximal surface perpendicular to the margin irrespective of incisal depth. There had correlation between fracture strength and fractured surface area.

제주도 양식넙치, Paralichthys olivaceus의 스쿠티카충병 발생 동향

진창남,이창훈,오상필,정용욱,송춘복,이제희,허문수 한국어병학회 2003 한국어병학회지 Vol.16 No.2

The research was carried out to know the occurrence trend of scuticociliatosis and mortality of fingerlings in flounder. The diseased fish were collected from on-land rearing farms and hatcheries of flounder in Jeju Island form January 1991 to December 2001. Occurrence of scuticociliatosis was about 10% of total occurred diseases for 1991 to 1996, but increased to 34.5% in 2001. Although monthly occurrence of seuticociliatosis was not related to season from 1999 to 2001, the highest occurrence was revealed in July and August. Mixed infections of bacteria including Vibrio sp., Edwardsiella tarda, Streptococcus sp., and Flexibacter sp., with seuticociliates were observed. Among the bacteria, Vibrio sp., was the highest frequency(40.1%), and the lowest one(10.1%) was Streptococcus sp., Mortality of fingerlings by seuticociliates was different sharply according to size of fish. Mortality of infected fingerlings below 7㎝ of total length was 53.8%, while that of normal fingerling above 7㎝ of total length was 13.2%. When fish were grown above 25㎝, mass mortality by seuticociliates infection was decreased markedly.

인체 체액내 황색포도상구균의 증식과 철 획득 기전

신성희,이강길,이명희,양남웅,임용,김진호 대한감염학회 2000 감염 Vol.32 No.5

마우스 종양발생에서 Nitric Oxide의 역할에 관한 연구 Ⅲ : Helicobacter pylori에 의해 유발된 마우스 위암에서 염증매개인자의 역할 The role of inducible nitric oxide synthase and cyclooxygenase-2 in H. Pylori-associated gastric carcinogenesis

남기택,오상연,조현무,이국경,강진석,제정환,최미나,한상욱,김대용,장동덕,양기화,안병우 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

feficotorfer fyf☞ri(Hp)가 위암파 관련이 있다는 역학적인 증거는 많이 있지만 이에 대한 정확한 기전에 대해선 밝혀져 있지 않고 있으며 실험동물 모델도 적절하지 못한 것으로 알려져있다. 본 실험에서는 위암의 원인으로 알려져 있는 f, fyforf'(Hp)를 이용하여 마우스에서 위암 모델을 확립하고 만성염증과정 중에 생성되는 리0와 COX-2 등의 발현이 위암발생에 미치는 명향을 통하여 예방과 치료를 위한 점근을 시도하고자 하였다. 마우스를 7군으로 나누어서 1, 2, 3, 4군의 등물은 MNU를 증류수에 200ppm 농도로 음수병득 이용하띤 10주간 격주로 투여하였으며 MHU 음술 투여 1주 휴씩 후 배양한 f. fyrofi 를 약 109cru/rfll 로 맞춰 한 마리당 0.1ml 씩 이틀 간격으로 세 번에 걸쳐 하룻방 금식시킨 1, 2, 3, 5, 6, 7군기 마우스의 위장에 투입하떴다. 균 투입을 마친 후 다응 날부터 2군쏙 6군은 iNOS 억제제인 aminoguanidine(AG)을 음수병으로 툰여하였으며 3군과 7군은 COX-2 척제제인 nimesulide(NSD)를 투여하였다. 위의 종양발생양상을 샅최보면 bfNU와 Hp만을 투여한 1 관 ; (hfNU +Hp), 2군 : iNO을 inhibitor 투여군(MNU+HP+AG'1. 3군 ;CO딘-2 Inilibitor 투여군(MNU누Hp누 NSD), 4군 ,MNlf 단독투여군, 5군 ;Hp 단독투여춘, 6군 ; 러p 단독에 AG투여군, 7군 , Hp 단독에 NSD투여군의 종양발샐을은 각각 쁜.Bff(l1/16), 70.6%f12/ti), 했.9ff(7/18), 10%(1/10), Off(O/IS)0%(O/S), 0%(O/5)의 발쟁율을 보여 iNOS 억제제인 AC은 좁양발생을 억계하지 못하였으며, COX-2억제제인 NSD 는 종양발생을 유의적으로 감소시켰다. 콩양발생개수에서는 2.62±0.36, 1.41츠0.14, 0.44 르0.12, 0.10±0.10을 보여 AC와 NSD에서 유의성 있게 발생개수를 줄였다. Hp 단독투여에 의해즌는 종양발생이 나타나지 않았으며 HP+AG, Hp+ IfSD 추여군에콕 시험증료 시점에 약물에 의해 Hp의 제균효과가 있는지의 여부를 확인끓기 위하여 PCR을 이용하여 확인한 결과 모두 양성인 것으로 나타나 Hp의 제균효과에 의한 촐양발생 억제가 일어나지는 않았다. 위의 결과로 볼 때 Hp는 위암발생을 촉진하는 것으로 나타났고 딘p 감염시 매개되는 염증인자를 억제하였을 때 종양발생을 억제하는 것으로 위암 발생에서 염증매개인자는 종양을 촉진하는 것으로 나타났으며 it,705 억제제쓱 COX-』 억제제의 위알 예밭효과fl는 효과적일 것으로 사료된다 In spite of a large volume of epidemiological evidence indicating significant relationship between H. pylori infection and gastric adenocarcinoma, a doubt still exists on an elevated risk of stomach cancer by H. pylori infection due to lack of direct evidence of their exact mechanistic link. It is, therefore, essential to have an appropriate animal model for detailed analysis of the role of H. pylori played in gastric carcinogenesis. There is a wealth of evidence to support that over production of inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2) is involved in the pathogensis of various cancer in both rodents and humans. The aim of this study was to establish a mouse model for H. pylori-associated gastric carcinogenesis and to identify the role of inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2) played during the gastric carcinogenesis in mice. Eighty-three specific pathogen free, six-week-old male C57BL/6 mice were randomly divided into seven groups. Animals of the group 1, 2, 3, 4 were given MNU in their drinking water at the concentration of 200 p.p.m. for total five cycles of one-week regimen with one-week pause. After completion of MNU administration, they were given autoclaved distilled water for one weeks, and groups 1, 2, 3, 5, 6, 7 were inoculated with H. pylori. After completion of H. pylori. inoculation, groups 2 and 6 were given aminoguanidine in their drinking water at concentration of 1000p.p.m. and animals of group 3 and 7 were given the diet containing 200 ppm nimesulide at 12 weeks of age. All animals were killed at 50 weeks of age. The incidences of the glandular stomach tumors in the group 1, 2, 3 and 4 were 87.5%(14/16), 76.4%(13/17), 44.4(8/18), 10.0%(1/10), respectively and the tumor incidence of group 3(MNU→Hp+nimesulide) was significantly lower than those of group 1(MNU→Hp) at the value of P<0.01. The average numbers of tumors of group 2(MNU→Hp+AG : 1.41±0.24) and group 3(MNU→Hp+nimesulide : 0.44±0.12) were significantly lower than those of group 1(MNU→Hp : 2.62±0.36) at the value of P<0.05. Therefore, overproduced iNOS and COX-2 plays an important role in mice gastric carcinogenesis. We concluded iNOS and COX-2 inhibitor have good effects on gastric carcinogenesis.