後天性 免疫缺乏症 感染實態에 關한 硏究

龍群鎬,申榮午,尹在得,李雄洙,朴貴禮,徐敎一,崔貞喜,奇美京,金成順,白善榮,南廷球,李承旭 국립보건연구원 1989 국립보건원보 Vol.26 No.

Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

Kee, Seung-Jung,Kwon, Yong-Soo,Park, Yong-Wook,Cho, Young-Nan,Lee, Sung-Ji,Kim, Tae-Jong,Lee, Shin-Seok,Jang, Hee-Chang,Shin, Myung-Geun,Shin, Jong-Hee,Suh, Soon-Pal,Ryang, Dong-Wook,Flynn, J. L. American Society for Microbiology 2012 Infection and immunity Vol.80 No.6

<B>ABSTRACT</B><P>Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious pathogens. However, little is known about the detailed information of NKT cells in patients withMycobacterium tuberculosisinfection. The aims of this study were to examine NKT cell levels and functions in patients with activeM. tuberculosisinfection, to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for the poor response to α-galactosylceramide (α-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the proliferative responses of NKT cells to α-GalCer were also lower in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls. Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, the poor response to α-GalCer inM. tuberculosis-infected patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in NKT cells. Notably,M. tuberculosisinfection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to α-GalCer. This study shows that NKT cell levels and functions are reduced inM. tuberculosis-infected patients and these deficiencies were found to reflect the presence of active tuberculosis.</P>

Clinical implications of endoscopic ultrasonography non-traversability in patients with locoregional esophageal cancer receiving multimodality therapy

( Charles J. Cho ),( Ho June Song ),( Gin Hyug Lee ),( Kee Don Choi ),( Yong-hee Kim ),( Jin-sook Ryu ),( Sung-bae Kim ),( Jong Hoon Kim ),( Seung-il Park ),( Hwoon-yong Jung ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.3

Background/Aims: Approximately 30% of esophageal cancer (EC) patients cannot complete endoscopic ultrasonography (EUS) due to malignant stricture (EUS non-traversability). This study examines clinical implications of EUS non-traversability in patients with advanced locoregional squamous EC receiving preoperative chemoradiotherapy (CRT) followed by esophagectomy. Methods: We retrieved data on 89 consecutive patients with advanced locoregional squamous EC (stage II or III). Relevant clinical and tumor-specific parameters were reviewed retrospectively. Significant factors affecting survival was determined by Cox regression analysis. Results: EUS non-traversable EC was observed in 26 of 89 patients (29.2%). Median serum albumin level (3.6 g/dL vs. 3.9 g/dL, p = 0.028), tumor length (6.0 cm vs. 4.0 cm, p = 0.002), and percentage of clinical stage III disease (65.4% vs. 38.1%, p = 0.019) were significantly different between the patients with EUS non-traversable and traversable EC, respectively. Patients with EUS non-traversable EC demonstrated a significantly lower 5-year overall survival than patients with EUS traversable EC (30.8% vs. 49.3%, p = 0.023). In multivariate analysis, weight loss ≥ 10% (p = 0.033), EUS non-traversability (p = 0.003), non-response to preoperative CRT (p = 0.002), and incompletion of esophagectomy (p = 0.002) were significant negative factors of survival. Conclusions: EUS non-traversability has significant negative prognostic implications in patients with advanced locoregional squamous EC receiving preoperative CRT followed by esophagectomy.

인공관절 주위 골용해에서 관절액의 RANKL/OPG 발현

김용식(Yong Sik Kim),최남용(Nam Yong Choi),이기행(Kee Haeng Lee),김영훈(Young Hoon Kim),한석구(Suk Ku Han),William J. Maloney 대한정형외과학회 2004 대한정형외과학회지 Vol.39 No.7

목적: 골관절염 환자와 골용해로 인공 관절 재치환술을 받은 환자의 관절액에서 Receptor Activator of NF-кB Ligand (RANKL), Osteoprotegerin (OPG) 및 염증 전구 단백질의 발현 차이를 관찰하고자 하였다. 대상 및 방법: 47예, 47명의 고관절 혹은 슬관절 인공 관절 치환술 환자를 대상으로 하였으며, 각각 4군으로 나누어 제1군은 골관절염 환자 15예, 제2군은 골용해 없이 재치환술을 시행한 15예, 제3군은 광범위한 골용해로 재치환술을 시행한 17예와 제2군과 3군을 합해 제4군으로 정하고 수술 중 관절액을 채취하여 RANKL, OPG, IL-1β IL-6과 TNF-α 단백질의 양을 enzyme-linked immunoassay (ELISA)법을 이용하여 측정 비교하였다. 결과: RANKL은 각군 간 유의한 차이가 없었으나, OPG는 제1군에 비해 제2, 3군에서 크게 증가되었다(2.2-3.9배)(p<0.0001). IL-lβ는 제1군에 비해 제2, 3, 4군에서 유의한 증가를 보였고, 특히 제3군에서 가장 높게 측정되었다(12.1배) (p<0.0001). IL-6은 골용해가 있는 제3군이 제1, 2군에 비해 2배 증가하였고, TNF-α는 제1군에 비해 제3군에서 2배, 제4군에서 유의한 증가를 나타내었다(p=0.03). 결론: 일정 농도의 RANKL과 OPG의 감소 및 염증 전구 단백질의 증가로 파골 세포의 활성에 의한 인공 관절 치환술 후 관절물 주위 골용해가 발생할 것으로 사료된다. Purpose: This study evaluated the expression level of Receptor Activator of NF-кB Ligand (RANKL), Osteoprotegerin (OPG) and other pro-inflammatory cytokines in the osteoarthritic and peri prosthetic joint fluid in order to characterize the role of these regulatory proteins in peri prosthetic osteolysis. Materials and Methods: Joint fluid specimens taken from 47 patients undergoing hip or knee reconstructive surgery were analyzed by enzyme-linked immunoassay (ELISA) in order to determine the relative protein expression level of RANKL, OPG, IL-1β, IL-6 and TNF-a. The fluid from joints with osteoarthritis (15 cases, Group Ⅰ), implants revised without associated osteolysis (15 cases, Group Ⅱ) and failed implants with radiographically moderate to severe osteolysis (17 cases, Group Ⅲ) were compared. The fluids from all cases with implants (Group Ⅱ and Ⅲ) was combined (Group Ⅳ) and compared with the osteoarthritic joint fluids. Results: RANKL was present in all the fluids at similar concentrations. The OPG levels were significantly lower (2.2-3.9 fold) in Groups Ⅱ and Ⅲ than in Group Ⅰ (p<0.0001). The IL-1β concentration was significantly higher in Groups Ⅱ, Ⅲ and Ⅳ and with Group Ⅲ being the highest (12.1 fold) (p<0.0001). The IL-6 expression level was significantly higher in Group Ⅲ (2.0 fold) than in Groups Ⅰ and Ⅱ (p<0.0001). The TNF-α levels were 2.0 times higher in Group Ⅲ and significantly higher in all implant cases (Group Ⅳ) are analyzed(p=0.03). Conclusion: Permissive RANKL protein expression coupled with suppressed OPG levels and enhanced osteoclastogenic cytokine expression results in peri prosthetic osteolysis.

The Nuclear Immune Receptor <i>RPS4</i> Is Required for <i>RRS1^SLH1</i> -Dependent Constitutive Defense Activation in <i>Arabidopsis thaliana</i>

Sohn, Kee Hoon,Segonzac, Cé,cile,Rallapalli, Ghanasyam,Sarris, Panagiotis F.,Woo, Joo Yong,Williams, Simon J.,Newman, Toby E.,Paek, Kyung Hee,Kobe, Bostjan,Jones, Jonathan D. G. Public Library of Science 2014 PLoS genetics Vol.10 No.10

<▼1><P>Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific “avirulent” pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis <I>R</I> genes, <I>RPS4</I> (resistance to <I>Pseudomonas syringae</I> 4) and <I>RRS1</I> (resistance to <I>Ralstonia solanacearum</I> 1), function together to confer recognition of <I>Pseudomonas</I> AvrRps4 and <I>Ralstonia</I> PopP2. <I>RRS1</I> is the only known recessive NB-LRR <I>R</I> gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 <I>via Pseudomonas</I> type III secretion. The Arabidopsis <I>slh1</I> (<I>sensitive to low humidity 1</I>) mutant encodes an RRS1 allele (RRS1<SUP>SLH1</SUP>) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1<SUP>SLH1</SUP>-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify <I><U>su</U>ppressor of</I><U>s</U>l<U>h</U>1 <I><U>i</U>mmunity</I> (<I>sushi</I>) mutants. We show that many <I>sushi</I> mutants carry mutations in <I>RPS4</I>, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an <I>Agrobacterium</I>-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1<SUP>SLH1</SUP> is required for RRS1<SUP>SLH1</SUP> function. We also recapitulate the dominant suppression of RRS1<SUP>SLH1</SUP> defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1<SUP>SLH1</SUP> shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector.</P></▼1><▼2><P><B>Author Summary</B></P><P>How plant NB-LRR resistance proteins and the related mammalian Nod-like receptors (NLRs) activate defense is poorly understood. Plant and animal immune receptors can function in pairs. Two Arabidopsis nuclear immune receptors, RPS4 and RRS1, confer recognition of the unrelated bacterial effectors, AvrRps4 and PopP2, and activate defense. Using delivery of PopP2 into Arabidopsis leaf cells <I>via Pseudomonas</I> type III secretion, we define early transcriptional changes upon RPS4/RRS1-dependent PopP2 recognition. We show an auto-active allele of RRS1, RRS1<SUP>SLH1</SUP>, triggers transcriptional reprogramming of defense genes that are also reprogrammed by AvrRps4 or PopP2 in an RPS4/RRS1-dependent manner. To discover genetic requirements for RRS1<SUP>SLH1</SUP> auto-activation, we conducted a suppressor screen. Many <I>suppressor of</I> slh1 <I>immunity</I> (<I>sushi</I>) mutants that are impaired in RRS1<SUP>SLH1</SUP>-mediated auto-activation carry loss-of-function mutations in RPS4. This suggests that RPS4 functions as a signaling component together with or downstream of RRS1-activated immunity, in contrast to earlier hypotheses, significantly advancing our understanding of how immune receptors activate defense in plants.</P></▼2>

Long-Term Survival and Tumor Recurrence of Patients with Superficial Esophageal Cancer after Complete, Non-Curative Endoscopic Resection: a Single Center Case Series

Ji Wan Lee,Charles J. Cho,Do Hoon Kim,Ji Yong Ahn,Jeong Hoon Lee,Kee Don Choi,Ho June Song,Sook Ryun Park,Hyun Joo Lee,Hyun Joo Lee,Gin Hyug Lee,Hwoon-Yong Jung,Sung-Bae Kim,Jong Hoon Kim,Seung-Il Par 대한소화기내시경학회 2018 Clinical Endoscopy Vol.51 No.5

Background/Aims: To report the long-term survival and tumor recurrence outcomes in patients with superficial esophageal cancer(SEC) after complete non-curative endoscopic resection (ER). Methods: We retrieved ER data for 24 patients with non-curatively resected SEC. Non-curative resection was defined as the presence ofsubmucosal and/or lymphovascular invasion on ER pathology. Relevant clinical and tumor-specific parameters were reviewed. Results: The mean age of the 24 study patients was 66.3±8.3 years. Ten patients were closely followed up without treatment, while14 received additional treatment. During a mean follow-up of 59.0±33.2 months, the 3- and 5-year survival rates of all cases were90.7% and 77.6%, respectively. The 5-year overall survival rates were 72.9% in the close observation group and 82.1% in the additionaltreatment group (p=0.958). The 5-year cumulative incidences of all cases of recurrence (25.0% vs. 43.3%, p=0.388), primary ECrecurrence (10.0% vs. 16.4%, p=0.558), and metachronous EC recurrence (16.7% vs. 26.7%, p=0.667) were similar between the twogroups. Conclusions: Patients with non-curatively resected SEC showed good long-term survival outcomes. Given the similar oncologicoutcomes, close observation may be an option with appropriate caution taken for patients who are medically unfit to receive additionaltherapy

Gastric Cancer Caused by Adenoma: Predictive Factors Associated with Lesions Other Than the Expanded Indications

( Seong Hwan Park ),( Kee Don Choi ),( Kyoungwon Jung ),( Yangsoon Park ),( Sunpyo Lee ),( Eun Jeong Gong ),( Hee Kyong Na ),( Ji Yong Ahn ),( Kee Wook Jung ),( Jeong Hoon Lee ),( Do Hoon Kim ),( Ho J 대한간학회 2018 Gut and Liver Vol.12 No.3

Background/Aims: We aimed to investigate whether the current indications for curative endoscopic resection (ER) of gastric cancer (GC) can be applied to GC caused by adenoma. Additionally, we attempted to identify factors predictive of lesions subsequently found in addition to the expanded indications for ER. Methods: We retrospectively analyzed 342 patients diagnosed with GC caused by adenoma who underwent ER at a single tertiary center between February 2011 and December 2014. The gross whole tumor size was measured using the endoscopically resected specimen. The microscopic whole tumor size was measured using mapping paper. The estimated cancer size was calculated using the microscopic whole tumor size and the square root of the carcinoma component. Results: A gross whole tumor size ≥3 cm, carcinoma component ≥35%, and gross ulceration were predictive of lesions other than the expanded indications for ER. The overall rate of lymph node metastasis was 0.3% (1/327), which only occurred in one patient with a lesion other than the expanded indications (4.5%, 1/22). Conclusions: The current indications for curative ER in GC can be applied to GC caused by adenoma. In cases suspected of having lesions other than the expanded indications, patients should be cautiously selected for ER to reduce the risk of an inappropriate procedure. (Gut Liver 2018;12:246-254)

Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping

Han, Sang Won,Kim, Yong-Jae,Ahn, Seong Hwan,Seo, Woo-Keun,Yu, Sungwook,Oh, Seung-Hun,Nam, Hyo Suk,Choi, Hye-Yeon,Yoon, Sung Sang,Kim, Seo Hyun,Lee, Jong Yun,Lee, Jun Hong,Hwang, Yang-Ha,Lee, Kee Ook,J Korean Stroke Society 2017 Journal of stroke Vol.19 No.3

<P><B>Background and Purpose</B></P><P> To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms. </P><P><B>Methods</B></P><P> This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke. </P><P><B>Results</B></P><P> The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60–2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26–1.79). </P><P><B>Conclusions</B></P><P> Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.</P>

A case of Degos` disease(Malignant atrophic papulosis,MAP) presenting with abdominal angina and widespread skin lesions (초)

( Hyo Kyung Choi ),( Dong Kyung Chang ),( Yeun Jung Lim ),( Kee Taek Jang ),( Jae J. Kim ),( Hee Jung Son ),( Young Ho Kim ),( Poong Lyul Rhee ),( Jun Haeng Lee ),( Jin Yong Kim ),( Jong Chul Rhee ) 대한내과학회 2008 대한내과학회 추계학술대회 Vol.2008 No.-

A case of Degos` disease(Malignant atrophic papulosis, MAP) presenting with abdominal angina and widespread skin Lesions (초)

( Hyo Kyung Choi ),( Dong Kyung Chang ),( Yeun Jung Lim ),( Kee Taek Jang ),( Jae J. Kim ),( Hee Jung Son ),( Young HO Kim ),( Poong Lyul Rhee ),( Jun Haeng Lee ),( Jin Yong Kim ),( Jong Chul Rhee ) 대한내과학회 2008 대한내과학회지 Vol.75 No.1S