Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>

In vitro combinatorial anti-proliferative and immunosuppressive effects of <i>Brucea javanica</i> extract with CX-4945 and imatinib in human T-cell acute lymphoblastic leukemia cells

Jung, Jung-Il,Kim, Se Young,Park, Kyeong-Yong,Sydara, Kongmany,Lee, Sang Woo,Kim, Soon Ae,Kim, Jiyeon Elsevier 2018 BIOMEDICINE AND PHARMACOTHERAPY Vol.106 No.-

<P><B>Abstract</B></P> <P>Since 1970, the isolated and identified components of <I>Brucea javanica</I> (L.) Merr. have been known to contain anticancer effects, particularly antileukemic effect. In this study, the inhibitory effect of <I>Brucea javanica</I> (BJ) on cell growth and inflammation was confirmed in human T-cell acute lymphocytic leukemia (T-ALL) cells, and its efficacy as an antileukemic agent was verified. Our results showed that BJ extract induced caspase-dependent apoptosis of T-ALL Jurkat cells through inhibition of the CK2-mediated signaling pathway, while exerting no significant cytotoxicity in normal peripheral blood mononuclear cells. Moreover, BJ extract suppressed the NF-κB signaling pathway, thus, inhibiting the interleukin (IL)-2 expression induced by phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin (PHA). Notably, combined treatment with BJ extract plus CX-4945 or imatinib exerted enhanced inhibitory effects on T-ALL cell growth and IL-2 production. Overall, these results suggest that BJ extract can be a potent therapeutic herbal agent for T-ALL treatment and prevention of IL-2 mediated inflammatory immune responses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Brucea javanica</I> extract induces caspase-dependent apoptosis of T-ALL cells. </LI> <LI> <I>Brucea javanica</I> extract the PMA/PHA-mediated NF-κB signaling pathway and IL-2 production. </LI> <LI> <I>Brucea javanica</I> extract suppresses expression of CK2 subunits and Akt phosphorylation. </LI> <LI> Combined treatment exerts enhanced inhibitory effects on T-ALL cell viability and IL-2 production. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Genetic effect of <i>CCR3</i> and <i>IL5RA</i> gene polymorphisms on eosinophilia in asthmatic patients

Lee, June-Hyuk,Chang, Hun Soo,Kim, Ji Hyun,Park, Se-Min,Lee, Yong Mok,Uh, Soo Taek,Rhim, Taiyoun,Chung, Il Yup,Kim, Yong-Hoon,Park, Byung Lae,Park, Choon-Sik,Shin, Hyoung Doo Elsevier 2007 The journal of allergy and clinical immunology Vol.120 No.5

<P><B>Background</B></P><P>Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.</P><P><B>Objective</B></P><P>We investigated the association of polymorphisms in <I>CCR3</I> and <I>IL5RA</I> with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression.</P><P><B>Methods</B></P><P>Polymorphisms in <I>CCR3</I> and <I>IL5RA</I> were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor α (IL-5Rα) protein expression on eosinophils was measured by means of flow cytometry.</P><P><B>Results</B></P><P>Although polymorphisms in <I>CCR3</I> were not associated with asthma susceptibility, the <I>CCR3</I> haplotype <I>ht2</I> showed a negative gene dose effect on the eosinophil count (<I>P</I> = .003–.009). <I>IL5RA c.−5091G>A</I> was weakly associated with eosinophil count. The effects of <I>ht2</I> were greater when paired with <I>IL5RA c.−5091A</I> (<I>P</I> = .001–.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without <I>ht2</I> than in those with <I>ht2</I>. Asthmatic patients with the <I>IL5RA c.−5091A</I> allele showed higher IL-5Rα expression than those who were homozygous for the G allele.</P><P><B>Conclusion</B></P><P>The genetic association between <I>CCR3</I> polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the <I>CCR3</I> polymorphisms were paired with polymorphisms in <I>IL5RA</I>. The protein expression levels of CCR3 and IL-5Rα on peripheral blood eosinophils are associated with the polymorphisms on their own genes.</P><P><B>Clinical implications</B></P><P>The identification of single nucleotide polymorphisms and haplotypes of <I>CCR3</I> and <I>IL5RA</I> might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.</P>

폐포 대식세포 및 단핵구가 Interleukin-2 Enhanced Natural Killer 및 LAK Activity에 미치는 영향

조철호 ( Jo Cheol Ho ),김병일 ( Kim Byeong Il ),김세규 ( Kim Se Gyu ),천선희 ( Cheon Seon Hui ),김형중 ( Kim Hyeong Jung ),장준 ( Jang Jun ),안철민 ( An Cheol Min ),김성규 ( Kim Seong Gyu ),이원영 ( Lee Won Yeong ),윤정구 ( Yun J 대한내과학회 1992 대한내과학회지 Vol.42 No.5

Alveolar macrophages (AM) are thought to function as primary effector cells against tumors growing in the lung. Systemic administration of lymphokine activated killer (LAK) cells and IL-2 resulted in partial antitumor response in patients with advanced cancer. LAK activity is influenced by various factors. We studied the effects of AM and blood monocytes from healthy donors on IL-2 enhanced NK activity against K-562 cells and LAK activity against Raji cells utilizing a 4h ^(51)Cr release assay. The following results were obtained: 1) The addition of different doses of human blood monocytes showed no suppression or enhancement of IL-2 enhanced NK and LAK activity. 2) The addition of high dose of AM (Lymphocyte: AM=1:1) significantly suppressed IL-2 enhanced NK activity. Smaller doses of AM (Lymphocyte: AM= 10:1and 100:1) did not suppress IL-2 enhanced NK activity. 3) The addition of high dose of AM (Lymphocyte: AM = 1:1 and 10:1) significantly suppressed LAK activity. The smallest dose of AM (Lymphocyte: AM= 100:1) did not suppress LAK activity. In conclusion, IL-2 enhanced NK and LAK activity were dose-dependently suppressed by human alveolar macrophages. However IL-2 enhanced NK and LAK activity were not suppressed by blood monocytes.

Electrical, Thermal, and Thermoelectric Transport Properties of Se-doped Polycrystalline Re2Te5

Se Woong Lee,Okmin Park,Hyun-Sik Kim,Won-Seon Seo,Sang-il Kim 대한금속·재료학회 2022 대한금속·재료학회지 Vol.60 No.12

Re2Te5 is considered a potential thermoelectric material because of its intrinsically low thermalconductivity, due to its complex crystal structure. Herein, a series of Se-doped Re2Te5 (Re2Te5-xSex, x = 0, 0.2,1, and 2) samples were synthesized, and their electrical and thermal transport properties were investigated. Pure orthorhombic Re2Te5 phases were successfully synthesized without any impurities for all compositions,and the continuous decrease in the calculated lattice parameters confirmed the substitution of Se atoms atthe Te sites. A maximum power factor of 0.135 mW/mK2was achieved for the sample with x = 0.2 at 880 K,mainly due to the increase in carrier concentration and electrical conductivity. The lattice thermalconductivity significantly decreased for all doped samples, which was attributed to the point defect phononscattering caused by Se doping. The thermoelectric figure of merit, zT reached a maximum value of 0.20 at880 K for Re2Te4.8Se0.2 (x = 0.2) sample, which was approximately 22% higher than that of the pristine Re2Te5sample. The weighted mobility, quality factor, and expected zT were calculated to evaluate the optimizationof the power factor and zT.

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

국가직업능력표준 실용화를 위한 제도화 방안

나승일,김주섭,김주일,정연앙,구자길,김강호,문세연 한국농업교육학회 2007 농업교육과 인적자원개발 Vol.39 No.1

이 연구의 목적은 일-교육훈련-자격이 연계될 수 있도록 노동부의 국가직업능력표준을 국가차원에서 개발·운영·관리될 수 있는 제도화 방안을 마련하는데 있었다. 연구목적 달성을 위해 문헌고찰 및 내용분석, 포커스그룹인터뷰를 실시하였고, 연구결과의 타당성 확보를 위해 전문가협의회 및 공청회를 실시하였다. 국가직업능력표준 제도화는 표준의 실용화를 제고할 수 있도록 관련용어 정의, 총괄기구, 표준개발 및 승인, 표준 활용에 관한 인프라 구축에 필요한 사항이 규정되도록 관계 법령을 정비하는 것이다. 표준 제도화를 위해 다음과 같은 사항이 관계 법령에 명시되도록 해야 한다. ① 표준 제도화를 위해 직업, 직업능력, 직무, 표준 등을 관련법에 정의해야 한다. ② 국가직업능력표준 관련 부처 및 다양한 이해당사자의 참여를 기반으로 한 국가직업능력표준 사업 전담 조직을 설치하고, 표준사업에 대한 자문과 심의를 담당할 수 있는 위원회를 구축한다. ③ 다양한 산업분야 단체가 표준개발의 주체가 될 수 있도록 지원하고, 표준의 수준 설정을 통해 직종 내 수직적 경력개발을 촉진하며, 개발된 표준에 대한 지속적인 관리와 현장적합성을 승인하는 체제를 구축해야 한다. ④ 국가직업능력표준은 산업현장에서는 인력을 채용하고 관리하는 기준으로, 교육훈련에서는 교육과정을 개발하고 교과목 및 교재를 개발하며 현 교육과정을 평가하는 기준으로, 자격체계와는 표준의 자격화, 새로운 자격설계, 자격의 출제기준으로 활용될 수 있도록 지원해야 한다. 이를 위해 국가기술자격법, 근로자직업능력개발법, 산업인력공단법 등 관계 법령을 개정하거나 국가직업능력표준에 관한 특별법을 제정할 필요가 있다. 한편, 국가직업능력표준 제도화 단계에 따른 구체적인 추진과제와 이를 실현하기 위한 정책적 제언을 제시하였다. The purpose of this study was to develop the institutionalization that NOS(National Occupational Standard) was developed, operated and managed for linking with work, training and qualification. To achieve the purpose, literature reviews, contents analysis and focus group interview were conducted, and experts council and a public hearing were executed. The institutionalization is the legislation consolidation to regulate details related infra construction as follows for improving utilization of NOS. ① It should be defined occupation, occupational competency, job, standards and so forth on the related laws. ② A organization which take exclusive charge with and a council which consult and deliberate on NOS projects should be established through the cooperation between stakeholder and government organization. ③ It should be supported that various industrial parties including SHRDC are the main body for development of NOS, promoted vertical career development by occupation through establishing level of NOS, and established system that manage continually and approve practical application of NOS. ④ It should be supported that NOS is used as a criterion for recruiting and managing workforce, a criterion for developing and evaluating curriculum and educational materials in training, having qualification for itself, designing for new qualification, and a criterion for setting questions for a qualifying examination. To improve utilization of NOS, It need to be consolidated the related laws including National Technical Qualifications Act and Workers' Vocational Competency Development Act or to be enacted a special law on NOS. Moreover, this study suggested action plan according to the stages of institutionalization, and political proposal for effective actualization of action plan.

관절염 모델에서 가미청열사습탕(加味淸熱瀉濕湯)의 진통 및 소염 효과에 관한 연구

김일현 ( Il Hyun Kim ),이하일 ( Ha Il Lee ),이세원 ( Se Won Lee ),권영미 ( Young Mi Kwon ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2015 한방재활의학과학회지 Vol.25 No.1

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund``s adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-α and IL-1β in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases. (J Korean Med Rehab 2015;25(1):27-44)

체성감각유발전위검사를 이용한 척추기형교정수술 시의 수술중 감시

김철,이창헌,김창효,석세일,김진혁,김원중,홍기혁 大韓再活醫學會 1999 Annals of Rehabilitation Medicine Vol.23 No.3

특수 언어발달 장애 환아의 임상 및음향음성학적 특성연구

김연희,박세훈,신용일,김찬양,김현기,김정수 大韓再活醫學會 2000 Annals of Rehabilitation Medicine Vol.24 No.1