1995~96년도 전국 모성사망원인 조사

박정한,서경,박문일,박중신,한영자,도세록 한국모자보건학회 1999 한국모자보건학회지 Vol.3 No.2

Blockade of indoleamine 2,3-dioxygenase protects mice against lipopolysaccharide-induced endotoxin shock.

Jung, In Duk,Lee, Min-Goo,Chang, Jeong Hyun,Lee, Jun Sik,Jeong, Young-Il,Lee, Chang-Min,Park, Won Sun,Han, Jin,Seo, Su-Kil,Lee, Sang Yong,Park, Yeong-Min Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.5

<P>Suppression of an excessive systemic inflammatory response is a promising and potent strategy for treating endotoxic sepsis. Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan catabolism, may play a critical role in various inflammatory disorders. In this study, we report a critical role for IDO in the dysregulated immune response associated with endotoxin shock. We found that IDO knockout (IDO(-/-)) mice and 1-methyl-D-tryptophan-treated, endotoxin-shocked mice had decreased levels of the cytokines, TNF-alpha, IL-6, and IL-12, and enhanced levels of IL-10. Blockade of IDO is thought to promote host survival in LPS-induced endotoxin shock, yet little is known about the molecular mechanisms that regulate IDO expression during endotoxin shock. In vitro and in vivo, IDO expression was increased by exogenous IL-12, but decreased by exogenous IL-10 in dendritic cells and splenic dendritic cells. Interestingly, whereas LPS-induced IL-12 levels in serum were higher than those of IL-10, the balance between serum IL-12 and IL-10 following challenge became reversed in IDO(-/-)- or 1-methyl-D-tryptophan-treated mice. Our findings demonstrate that the detrimental immune response to endotoxin shock may occur via IDO modulation. Restoring the IL-12 and IL-10 balance by blocking IDO represents a potential strategy for sepsis treatment.</P>

Genetic polymorphism of DOCK8, IL17RA and KLK12 in Koreans with atopic dermatitis and allergic march

( Hye Sung Han ),( Jae Min Kim ),( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Seong Jun Seo ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Atopic dermatitis (AD) is one of the most common childhood diseases and has a complex etiology involving genetic and environmental factors. Thus, a broad understanding of genetic background is needed for early diagnosis of AD. Objectives: The purpose of this study was to identify of novel candidate functional genetic variants in Koreans with atopic dermatitis and allergic march. Methods: Whole-exome sequencing (WES) was performed in 20 AD and 20 AM Korean patients, and 40 Korean personal genome project (KPGP) controls. Sanger sequencing was carried out to validate found variants in 86 AD, 72 AM patients and 81 controls. Results: Three candidate variants of DOCK8 (rs529208), IL17RA (rs1248468), and KLK12 (rs3745540) were identified. rs529208 had no correlation with the development of AD but the AA genotype of DOCK8 had significantly increased total IgE level. rs1248468 had significantly increased risk of AD and the CA genotype of IL17RA had also increased total IgE level. rs3745540 was significantly associated with AD. Conclusion: DOCK8 (rs529208), IL17RA (rs1248468) and KLK12 (rs3745540) were deemed functionally interesting based on WES. Our case-control study suggests that the three variants detected in WES may enhance the risk of AD.

백혈병 마우스 모델의 동종골수이식에서 활성화된 자연살해세포들의 보충이 이식편대백혈병효과와 이식편대숙주반응에 미치는 영향

엄현석,한치화,박수정,김소연,정낙균,정대철,진종률,최일봉,양형모,서영훈,송현근,최인표,민우성,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 백혈병에서 동종골수이식 (allogeneic bone marrow transplantation)의 성공적 치료 효과를 얻기 위해서는 이식편대숙주반응 (graft-versus-host disease, GVHD) 발생의 극복과 재발의 방지가 중요한 과제이다. 골수를 역류원심성 세포분리 (counterflow centrifugal elutriation, CCE) 방법으로 분리하여 얻은 rotor off (R/O) 세포분획은 T 세포의 수는 적지만 조혈모세포들을 다량 포함하고 있어 동종골수이식에서 주조직적합복합체 (major histocompatibility complex, MHC) 차이를 극복할 수 있고, 이식편의 생착 성공과 GVHD 발생 예방에 효과적이다. 그러나 골수로부터 T 세포를 제거하면 백혈병세포를 공격하는 이식편대백혈병 (graft-versus-leukemia, GVL) 효과가 감소되기 때문에 백혈병 재발의 빈도가 높다. 자연살해세포 (natural killer cell, NK cell)의 보충 첨가는 동종골수이식 후 GVHD 발생을 줄이면서 충분한 GVL 효과를 얻을 수가 있다. 따라서 저자는 분리 후 IL-2로 활성화시킨 NK 세포들을 골수 R/O 세포분획과 함께 백혈병 마우스 모델에 동종이식함으로써 GVHD와 GVL에 미치는 효과를 관찰하였다. 방법: Balb/c (H-2^(d)) 마우스에서 유래된 A20 (murine B-lymphoma/leukemia cell line, H-2^(d)) 백혈병 세포를 이식 2 일 전에 Balb/c 마우스에 주입하고, 치사량의 전신 방사선을 조사한 직후에 Balb/c 또는 C57BL/6 (H-2^(b)) 마우스의 골수 R/O 세포분획을 꼬리정맥을 통하여 주입하였다. 이들은 모두 이식 후 6-8 주 이내에 사망하였다. 동종이식의 대조군 (n=9)에는 1 × 10^(7)의 R/O 세포분획만을 주입하였고, 실험군 (n=9)에는 C57BL/6 마우스의 비장세포들로부터 단클론항체들을 이용한 negative selection방법으로 분리한 후 IL-2로 활성화된 5 × 10^(5)의 NK 세포분획을 1 × 10^(7)의 R/O 세포분획과 함께 주입하였다. GVL 효과의 판정은 이식 후 14 일과 28 일 째 되는 날 마우스에서 골수, 비장, 간 등을 얻어 백혈병 세포들의 침윤을 조직학적으로 관찰하였으며, GVHD의 정도는 육안적 관찰법으로 평가하였다. 결과: R/O 세포분획만을 이식한 대조군의 골수, 비장, 그리고 간 조직에서는 A20 백혈병 세포의 침윤이 각각 89% (8/9), 78% (7/9)와 22% (2/9)에서 관찰되었고, R/O 세포분획과 NK 세포분획을 함께 이식한 실험군에서는 비장과 간을 제외한 골수에서만 89% (8/9)에서 A20 백혈병 세포의 침윤이 관찰되어 두 군 사이에 장기별 분포의 차이를 볼 수 있었다 (P= 0.0001). 한편 GVHD는 두 군 모두에서 경하게 나타나서 유의한 차이는 없었다. 또한 생착 부전으로 사망한 마우스는 없었다. 결론: CCE를 이용하여 T 세포를 제거한 동종골수이식에서 NK 세포의 보충은 GVHD의 악화는 일으키지 않으면서, 백혈병의 진행을 억제하는 GVL 효과를 얻을 수 있었다. Background: Allogeneic bone marrow transplantation (BMT) with T cell-depleted marrow accompanies engraftment failure and relapse of leukemia by a loss of the graft-versus-leukemia (GVL) effect frequently, while it can prevent GVHD. Supplement of NK cells could prevent GVHD and enhance GVL effect in several murine allogeneis BMT models Roter off (R/O) cell fraction obtained by counterflow centriation elutriatio (CCO) contains small number of T cells and many hematopoietic stem cells. The aim of this study was to determine the effect of R/O cell fraction supplemented with IL-2 activated NK cells on GVL and GVHD within the leukemic mouse BMT model. Methods: Inoculation of A20 (H-2d, murine B-lymphoma/leukemia, Balb/c origin) cells into Balb/c mice via the tail vein 2 days prior to lethal total body irradiation (TBI) and infusion of the Balb/c BM or C57BL/6 (H-2b) R/O fraction were performed. It resulted in 100% mortality within 6 to 8 weeks. The irradiated mice in the control group were injected with 1 × 107 R/O cell fraction alone (n=9) and in the experimental group mice were injected with 1 × 107 R/O cell fraction plus 5 × 105 negatively selected IL-2 activated NK cell fractions of the spleens via the tail vein (n=9). On day 14 and 28 after BMT, the bone marrows, spleens, and livers of mice were harvested for histopathologic analysis of the infiltrations of leukemic cells. We then evaluated the GVHD within the mice. Results: A histopathologic study of the recipients receiving R/O fraction alone showed infiltration of leukemic cells, 89% (8/9) in bone marrows, 78% (7/8) in spleens, and 22% (2/9) in livers. The experimental group of mice showed only the infiltration of leukemic cells 89% (8/9) in bone marrows, not in spleens and livers. There were the organ differences of the leukemic cells infiltrations between the two groups (P=0.0001). There were no obvious differences in the GVHD scores between these two groups, and severe GVHD was not observed. There was no engraftment failure among groups. Conclusion: Thus, our findings suggest that R/O cell fraction obtained by CCE and supplemented with NK cells can promote GVL effect without mediating clinically overt GVHD in allogeneic BMT of mouse leukemia.

류마티스 활막염에 있어 염증매개물질에 의한 Transforming Growth Factor-β-inducible Gene-h3 (βig-h3) 생산 조절 기전

강영모 ( Young Mo Kang ),김성일 ( Sung Il Kim ),김정섭 ( Jeong Seup Kim ),유동완 ( Dong Wan You ),사금희 ( Kheum Hee Sa ),박은주 ( Eun Ju Park ),김성욱 ( Sung Uk Kim ),서재석 ( Jae Seok Seo ),한승우 ( Seung Woo Han ),남언정 ( Eon 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.2

Objective: To investigate the expression pattern of transforming growth factor-β-inducible gene-h3 (βig-h3) within rheumatoid synovial tissue and the regulation of βig-h3 synthesis in fibroblast-like synoviocyte (FLS). Methods: Synovial tissues obtained from patients with rheumatoid arthritis and osteoarthritis were obtained during joint replacement surgery. βig-h3 expression was evaluated with immunohistochemical stain. FLS was isolated from synovial tissues and stimulated with cytokines including TGF-β, TNF-α, IL-1β, IFN-γ, IL-6, IL-4, and IL-10. βig-h3 synthesis was measured using semiquantitative RT-PCR, ELISA, immunofluorescence stain, and flow cytometry. Results: Expression of βig-h3 was diffuse and abundant in both lining and sublining layers of rheumatoid synovium, which was more prominent than those of osteoarthritis. Production of βig-h3 in FLS was regulated by TGF-β1 in a dose-dependent manner and was highest at 5 ng/mL of TGF-β1. TNF-α and IL-1β upregulated the production of βig-h3 from FLS synergistically with TGF-β1 but other cytokines such as IL-4, IL-6, IL-10 did not affect. βig-h3 synthesis was efficiently inhibited by dexamethasone at higher dose (100 nM) but not by cyclosporine-A. Conclusion: Production of βig-h3, which is highly upregulated in rheumatoid synovitis, is differentially regulated by inflammatory cytokines.

Expression and regulation of inhibitor of DNA binding proteins <i>ID1</i>, <i>ID2</i>, <i>ID3</i>, and <i>ID4</i> at the maternal-conceptus interface in pigs

Han, Jisoo,Seo, Heewon,Choi, Yohan,Lee, Choongdeok,Kim, Meong Il,Jeon, Yubyeol,Lee, Joohyeong,Hong, Minsun,Hyun, Sang-Hwan,Lee, Eunsong,Ka, Hakhyun Elsevier 2018 Theriogenology Vol.108 No.-

<P><B>Abstract</B></P> <P>Inhibitor of DNA binding (ID) proteins, ID1, ID2, ID3, and ID4 are transcriptional regulators that have a helix-loop-helix (HLH) domain but not a basic DNA binding domain. ID proteins inhibit the functions of basic HLH transcription factors and regulate cell proliferation and differentiation. However, the expression and function of <I>ID1</I>, <I>ID2</I>, <I>ID3</I>, and <I>ID4</I> at the maternal-conceptus interface are not fully understood in pigs. Therefore, we determined the expressions of <I>ID1</I>, <I>ID2</I>, <I>ID3</I>, and <I>ID4</I> in porcine endometrium, conceptus, and chorioallantoic tissues. <I>ID1</I>, <I>ID2</I>, <I>ID3</I>, and <I>ID4</I> mRNAs were expressed in the endometrium, with lower levels of <I>ID1</I>, <I>ID2</I>, and <I>ID4</I> on Day 12 of pregnancy than during the estrous cycle. <I>ID1</I>, <I>ID2</I>, <I>ID3</I>, and <I>ID4</I> mRNAs were also detected in conceptus and chorioallantoic tissues during pregnancy. ID2 protein was mainly localized to luminal epithelia and weakly to vascular smooth muscle cells in the endometrium and conceptus trophectoderm. Increasing doses of interleukin-1β decreased levels of <I>ID2</I> mRNA, while estradiol-17β increased levels of <I>ID3</I> mRNA in endometrial explants. The expressions of <I>ID2</I> and <I>ID4</I> mRNAs were higher in endometria from gilts with somatic cell nuclear transfer-derived conceptuses compared with endometria from gilts carrying conceptuses derived from natural mating on Day 12. These results indicate that the expressions of ID family genes are dynamically regulated at the maternal-conceptus interface, suggesting that ID proteins may play critical roles in the regulation of endometrial epithelial cell function and conceptus development to support the establishment and maintenance of pregnancy in pigs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>ID1</I>, <I>ID2</I>, <I>ID3</I>, and <I>ID4</I> expression in porcine uterine endometrium is pregnancy status- and stage-specific. </LI> <LI> ID2 protein is detected primarily in endometrial LE cells. </LI> <LI> IL1B decreases the expression of <I>ID2</I> mRNA in endometrial tissues. </LI> <LI> The expressions of <I>ID2</I> and <I>ID4</I> mRNAs increase in endometria of gilts with SCNT-derived conceptuses. </LI> </UL> </P>

수리모형과 수치해석을 통한 만곡부 하천의 수리학적 특성 비교 고찰

서동일,최한규 강원대학교 산업기술연구소 2007 産業技術硏究 Vol.27 No.A

This study, regarding curved channel, was performed to compare and analyze hydraulic characteristics and the speed of water and water level for left bank and right bank through hydraulic model experiments and numerical analysis. Real channels that had characteristics of curved channel were selected as objectives. In order to easily operate one and two dimensional numerical analysis and comparison for total 2.4Km model channel, measuring point was set up as 200m. HEC-RAS model was applied as one dimensional numerical analysis program and SMS model was used as two dimensional numerical analysis program. In respect of speed of water, the average speed of water for right bank recorded 8.33m/s in a model experiment and 3.08m/s, 8.57m/s were average speed of water for right bank in one dimensional and two dimensional numerical analysis. The average speed of water of two dimensional numerical analysis was quite similar to that of model experiments. Also, as for water level, maximum observational errors between one and two dimensional numerical analysis for right and left bank of model experiments were 0.66m, 0.84m and 0.28m, 0.48m for each. It was found that two dimensional numerical analysis had a similar result to hydraulic model experiments. Accordingly, from the result of this study, two dimensional numerical analysis should be used rather than one dimensional numerical analysis, when numerical analysis for curved channel is conducted.

알쯔하이머 병의 분자 유전학

우성일,서한길 대한생물치료정신의학회 2001 생물치료정신의학 Vol.7 No.2

The sequencing of the amino acids in the β-amyloid and the cloning of the amyloid precursor protein(APP) gene were the breakthrough event in the molecular biologic researches about the Alzheimer’is disease. After then, the mutations in the APP gene, presenilin 1 gene and presenilin 2 *gene associated with the familial Alzheimer’s disease(FAD) were found. Also, the roles of APOLEε 4 as a risk allele and APOLE ε2 as a protective allele in late onset AD, were demonstrated. All of the mutations causing FAD were known to function through a common final pathway which involves the increase on fibrillogenic form af Aβ. The APOLE allele seems to influence the production, distribution and clearance of Aβ. Such expansion in the understanding of AD molecular genetics give hopes to the development of novel therapeutic modalities.

Activation of NKT Cells in an Anti-PD-1–Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells

Bae, Eun-Ah,Seo, Hyungseok,Kim, Byung-Seok,Choi, Jeongwon,Jeon, Insu,Shin, Kwang-Soo,Koh, Choong-Hyun,Song, Boyeong,Kim, Il-Kyu,Min, Byung Soh,Han, Yoon Dae,Shin, Sang Joon,Kang, Chang-Yuil American Association for Cancer Research 2018 Cancer Research Vol.78 No.18

<P>These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer.</P><P>PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with cancer across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances antitumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of patients with cancer to anti-PD-1 therapy remains low, providing an urgent need for optimization and improvement. In this study, we designed an anti-PD-1–resistant mouse tumor model and showed that unresponsiveness to anti-PD-1 is associated with a gradual increase in CD8 T-cell exhaustion. We also found that invariant natural killer T cell stimulation by the synthetic ligand α-galactosylceramide (αGC) can enhance the antitumor effect in anti-PD-1–resistant tumors by restoring the effector function of tumor antigen–specific exhausted CD8 T cells. IL2 and IL12 were among the cytokines produced by αGC stimulation critical for reinvigorating exhausted CD8 T cells in tumor-bearing mice and patients with cancer. Furthermore, we observed a synergistic increase in the antitumor effect between αGC-loaded antigen-presenting cells and PD-1 blockade in a therapeutic murine tumor model. Our study suggests NKT cell stimulation as a promising therapeutic strategy for the treatment of patients with anti-PD-1–resistant cancer.</P><P><B>Significance:</B> These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer. <I>Cancer Res; 78(18); 5315–26. ©2018 AACR</I>.</P>

성인의 급성 심장사에서 정상 심장례의 분석

강신몽,이원태,이한영,서중석,최영식,권일훈,정낙은 大韓法醫學會 2000 대한법의학회지 Vol.24 No.2

The authors analysed 53 cases of sudden cardiac death(SCD) without prominent structural abnormalies of heart out of witnessed 300 cases. Thirty four cases were associated with sleep and 19 with activity or rest. Twenty one cases were classified as having normal hearts, and the rest as structurally mild abnormal ones. Male was predominant, and almost of the victims were suffered in their twenties or thirties. All cases collapsed instantaneously or in very short time with various and not specific terminal symptoms. Inducing or trigger factors are not clarified in almost of the cases. Mechanisms or causes of death could not be defined clearly. We concluded that careful heart examination with detailed clinical history under the appropriate postmortem investigation system is only effective approach for the true mechanism and cause of death.