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>

자궁내막증 병변에서의 Cytokine mRNA의 발현 양상

이택후(Taek Hoo Lee),김광수(Gwang Soo Kim),김일규(Il Gyu Kim),전상식(Sang Sik Chun),조영래(Young Lae Cho) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.9

목적: 자궁내막증은 최근에 그 빈도가 급격하게 증가되고 있으나 아직까지 병인과 치료법이 확실하게 정립되지 못하고 있는 부인과 내분비의 대표적인 질환이다. 최근 들어서 자궁내막증 환자의 불임의 원인으로 cytokine이 밀접하게 관여됨이 밝혀지고 있고 자궁내막증의 병인으로 복강내로 역류된 월경혈에 의한 복강내의 국소적 염증에 대한 개체의 반응정도와 면역체계의 변화가 중요하게 인정되고 있으나 아직까지 정확한 기전은 밝혀져 있지 않기 때문에 이에 저자는 자궁내막증 환자의 복수 내에서의 cytokine의 정량측정과 골반내 자궁내막증 병변조직에서의 cytokine mRNA의 발현 양상을 조사하여 자궁내막증 환자의 병인분석을 시도하였다. 연구방법: 자궁내막증 진단을 받고 복강경 혹은 개복 수술을 받은 30명의 환자에서 총 60개의 자궁내막증 병변이라고 의심되는 조직을 채취하여 이를 RT-PCR법을 이용하여 Cytokine 유전자의 발현양상을 조사하였다. 또한 7례의 정상대조군과 23례의 자궁내막증 환자의 복수를 ELISA법을 이용하여 정량분석을 시도하였다. 결과: 자궁내막증 환자의 복수내에서 IL-6와 IL-10의 농도는 자궁내막증의 임상적 중증도에 따라서 의미있게 증가되어 있었으나 IFN-γ, TNF-α, IL-1β, 그리고 IL-5의 농도는 정상 대조군에 비해서 변화가 없었다. 모든 예의 심부 자궁내막증 병변조직과 표재성 자궁내막증 병변조직에서 IL-1β cytokine mRNA의 발현을 볼 수 있었다. IL-5와 IL-6은 표재성 병변 12개 중에서 각각 2개의 black lesion에서만 발현을 볼 수 있었으며 IL-10은 표재성 병변에서는 12개중 2개에서 그리고 심부성 병변에서는 8개중 1개의 조직에서만 발현되었다. IFN-γ는 표재성 병변에서는 전혀 발현이 없었으나 심부성 병변에서는 8개중 4개의 조직에서 발현이 되었으며 TNF-α는 표재성 병변에서는 red 및 black 병변에서 각각 1개의 조직에서만 발현이 되었으나 심부성 병변에서는 역시 8개중 4개의 조직에서 발현이 되었다. 결론: 표재성 병변이 골반강내에 착상하여 염증성 반응이 일어날 수 있는 원인이 제공되면 IL-1β 혹은 TNF-α같은 염증성 cytokine이 분비가 되며 이로 인해 생성되는 단핵세포의 chemotactic factor에 의해 대식세포의 증가와 활성화가 이루어지고 이어서 복강내에 IL-6 등의 cytokine이 증가되며 마지막으로 여러 가지 증가된 cytokine에 대한 반대 반응으로 IL-10이 증가됨을 추정할 수가 있겠으며 이러한 가정은 앞으로 cytokine을 이용한 치료적 응용의 기초적인 연구로서 중요한 의미를 제공할 수 있다고 하겠다. Objective: The pathogenesis of endometriosis is generally accepted that retrograde menstruation and alterations in the local pelvic immune environment. This study was performed to help elucidate what kind of role various cytokines might play in the pathogenesis of endometriosis. Method: Concentrations of peritoneal fluid cytokines were compared in 7 women with normal pelvic finding and 23 women with endometriosis by enzyme-linked immunosorbent assay(ELISA). The patterns of cytokine mRNA expression in 8 ovarian endometrioma and 12 superficial pelvic endometriosis lesions were investigated by reverse transcription-polymerase chain reaction(RT-PCR) amplification method. Result: Both IL-6 and IL-10 levels in peritoneal fluid specimens with endometriosis tended to be higher than normal. However, there were no significant differences between peritoneal fluid concentrations of IFN-γ, TNF-α, IL-1β, and IL-5 of women with and without endometriosis. The levels of IL-6 and IL-10 were significantly higher in peritoneal fluid of women with severe endometriosis compared to women with mild endometriosis. IL-1β mRNA was expressed in all of 8 deep and 12 superficial endometriosis lesions. IL-5 and IL-6 mRNA were expressed in only two black lesions respectively, however, both were not expressed in the all deep lesions. Expressions of IL-10 mRNA occurred in one red and one black lesion while this was expressed in only one of the deep lesions. TNF-α mRNA was expressed in one red and one black lesion of 12 superficial lesions compared with four of the deep lesions. There was the difference between kinds of increased cytokines in the peritoneal fluid and those of expressed cytokines in the endometriotic lesions of patients with endometriosis. Conclusion: This study supports the concept that local immunologic factors may be important in the pathogenesis and pathophysiology of endometriosis. The pattern of cytokine mRNA expression of endometriotic lesions would seem to indicate that proinflammatory cytokines such as IL-1β and TNF-α are responsible for the development or progression of endometriosis.

Triple costimulation via CD80, 4-1BB, and CD83 ligand elicits the long-term growth of Vγ9Vδ2 T cells in low levels of IL-2

Cho, Hyun-Woo,Kim, Su-Yeon,Sohn, Dae-Hee,Lee, Min-Ji,Park, Mi-Young,Sohn, Hyun-Jung,Cho, Hyun-Il,Kim, Tai-Gyu Federation of American Societies for Experimental 2016 Journal of Leukocyte Biology Vol.99 No.4

<P>Human gamma delta T cells play important roles in the regulation of infection and cancer. To understand the roles of costimulatory signals in activation and expansion ex vivo, V gamma 9V delta 2 T cells were grown with artificial APCs that express CD83, 4-1BB ligand, and/or CD32, which allowed a loading of alpha CD3 and alpha CD28 antibodies. The costimulatory signals through CD80, 4-1BB, and CD83 ligand in low levels of IL-2 triggered an explosive ex vivo proliferation of V gamma 9V delta 2 T cells capable of secreting high levels of IL-2, IFN-gamma, and TNF-alpha. Moreover, the triple-costimulatory signals cause augmented cell viabilities for long-term growth of V gamma 9V delta 2 T cells, resulting in phenotypic changes to CD272(-)CD45RA(+) effector memory-like cells. Notably, we observed that CD83 ligand signaling is crucial to promote ex vivo expansion, survival, and cytolytic effector functions of V gamma 9V delta 2 T cells. In contrast, 4-1BB signaling is moderately important in up-regulating surface molecules on V gamma 9V delta 2 T cells. Consequently, gd T cells stimulated in the presence of triple-costimulatory signals have diverse cytolytic effector molecules, including perforin, granzyme A, granzyme B, and Fas ligand, eliciting potent cytolytic activities against tumor cells. Overall, our results provide insights into the roles of costimulatory signals in manufacturing long-lived and fully functional V gamma 9V delta 2 T cells that could be useful against cancers.</P>

An optimized peptide vaccine strategy capable of inducing multivalent CD8 ⁺ T cell responses with potent antitumor effects

Cho, Hyun-Il,Jung, Soo-Hyun,Sohn, Hyun-Jung,Celis, Esteban,Kim, Tai-Gyu TaylorFrancis 2015 Oncoimmunology Vol.4 No.11

<P>Therapeutic cancer vaccines are an attractive alternative to conventional therapies for treating malignant tumors, and successful tumor eradication depends primarily on obtaining high numbers of long-lasting tumor-reactive CD8<SUP>+</SUP> T cells. Dendritic cell (DC)-based vaccines constitute a promising approach for treating cancer, but in most instances low immune responses and suboptimal therapeutic effects are achieved indicating that further optimization is required. We describe here a novel vaccination strategy with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine-polycytidylic acid (poly-IC) and anti-CD40 antibodies (TriVax) for improving the immunogenicity and therapeutic efficacy of DC-based vaccines in a melanoma mouse model. TriVax immunization 7–12 d after priming with antigen-loaded DCs generated large numbers of long-lasting multiple antigen-specific CD8<SUP>+</SUP> T cells capable of recognizing tumor cells. These responses were far superior to those generated by homologous immunizations with either TriVax or DCs. CD8<SUP>+</SUP> T cells but not CD4<SUP>+</SUP> T cells or NK cells mediated the therapeutic efficacy of this heterologous prime-boost strategy. Moreover, combinations of this vaccination regimen with programmed cell death-1 (PD-1) blockade or IL2 anti-IL2 antibody complexes led to complete disease eradication and survival enhancement in melanoma-bearing mice. The overall results suggest that similar strategies would be applicable for the design of effective therapeutic vaccination for treating viral diseases and various cancers, which may circumvent current limitations of cell-based cancer vaccines.</P>

고유량 고효율 혈액투석막 재사용의 임상경험

조현경,김승정,임병국,정혁준,최영일,마경애,신규태,김흥수,김도헌 대한신장학회 2001 대한신장학회잡지 Vol.20 No.3

측두골 골절 : 임상적 및 방사선학적 분석 Clinical and Radiological Analysis

조성원,최순관,조성진,김범태,신원한,윤일규,변박장 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

The objective of this study is to review of the incidence of temporal bone fractures and complications resulting from temporal bone fractures and to analyze the correlation between clinical and radiological findings. A series of 49 patients who were diagnosed temporal bone fracture with rhinorrhea, bloody otorrhea, admitted to Soonchunhyang University Chon-an Hospital from January 1997 to September 1999, were studied retrospectively. Clinical analyses were focused on age, sex, type of accident, external wound site, CSF leakage, hearing loss and facial nerve palsy. The high resolution CT scan consisted of a series of 3-mm thick sections through the temporal bone using the GE CT scanner (General Electric Inc.). In radiologic analyses, fracture types of temporal bone were divided into longtudinal fracture(LF), transverse fracture(TF) and mixed fracture(MF) respectively. The CT scans were examined for mastoid antral haziness(MH), middle ear cavity haziness(MeH), ossicular chain disruption(OD), otic capsule fracture(OF), pneumocephalus(Pn). The type of facial canal fracture was classified as fracture of internal auditory canal portion(FIAC), fracture of perigeniculate portion(FPG), fracture of tympanic portion(FT), fracture of mastoid portion(FM). The correlation between clinical and radiological findings was analysed. A total of 49 fractured temporal bones resulted in 9 CSF fistula, 23 hearing loss( 13 conductive type, 7 sensorineural type), 17 facial nerve injuries ranging from mild paresis to complete paralysis. The mose common etiology of the injury was from a motor vehicle accident(28%). The type of fracture observed on high resolution CT scanning was a LF in 39(78%) patients, a TF in 7(14%) patients and a MF in 3(6%) patients. The majority of fractures terminate in the floor of the middle cranial fossa in LF and passed lateral to the otic capsule in TF. Average time of onset of delayed facial palsy was 3.5 days. No patient developed prolonged otorrhea or meningitis during hospitalization and there was no requirement of surgical management. Hearing loss was the most common complication of temporal bone fracture(48%). Conductive hearing loss was associated with middle ear cavity haziness and ossiclular chain disruption. in temporal bone CT. A total of 29 cases facial canal fracture in temporal bone CT resulted in 14 perigeniculate portion(FPG), 12 tympanic portion(FT), 3 mastoid portion(FM). There was no correlation between radiological facial canal fracture and clinical facial nerve palsy. Four of 17 patients with facial nerve injury required facial nerve exploration under general anesthesia. We thought that prognosis and therapeutic planning in patients with temporal bone fractures were based on the clinical and radiological findings.

중세국어의 힘줌 풀이씨 뒷가지 연구

조일규 평택대학교 1996 論文集 Vol.8 No.-

정의 표현 풀이씨 뒷가지의 변천 (Ⅰ)

조일규 평택대학교 1999 論文集 Vol.13 No.-

이 글은 중세국어에서 근대국어에 나타난 정의 표현 풀이씨 뒷가지의 변천을 살피는 데 목적이 있다. 중세국어세어 생산성을 자진 정의 표현 뒷가지는 '-??/브, -??/??-, -ㅂ-, -갑/겁-, -얍/업-, -얍/엽-, -??/답-, -????-(>-??/도외-), -??/롭-, -??/로??-(>-??/로외-, -로??/의-)'등이 있다. 근대국에서의 생산성을 가진 정의 표현 뒷가지는 '??/브/부-, -ㅂ-, -갑/겁-', -압/업-, -얍/엽-, -답-, ??/도외-, -스럽-' 등이 있다. 이들 가지는 '-??/브, -??/??-, -ㅂ-' > '-??/브/부-, -ㅂ-', '-갑/겁-, -압/업-, -얍/엽-', > '-갑/겁-, -압/업-, -얍/엽-', '-??/답-, -????-(>-??/도외-), -??/롭-, -??/로??-(>-??/로외-, -로??/의-)' > ① '-답-, ??/도외-', ② '-??/랍/롭-, -??/로외-'가지로 변천 한다. '-스럽-'가지는 근대국어에서 처음 나타나 쓰인다. '-??/??-, -??/??-, -ㅂ-' > '??/브/부-, -q-'에서 '-??/??-가 사라진 것은 근대국어에서는 '??'이 TM이지 않음으로써 자연 '-??/??-'의 형태도 사라지게 된 것이고 중세국어에서는 보이지 않던 '-부-'가 '-??/브-'의 이형태로 근대국어에 나타나는 것은 '-브-'에서 둥근 입술 소리 되기의 현상을 입어 나타난 것이다. 중세국어에서 한 가지의 이행태로 쓰이던 '-??/답-, -????-(>-??/도외-), -??/롭-, -??/로??-(>-??/로외-, -로??/의-')가지는 근대국어에서 ①'-답-, -??/도외-', ②'-??/랍/롭-, -??/로외-' 가지로 나누어져 서로 다른 가지로 쓰인다.

현대국어에 나타난 정의 표현 풀이씨 뒷가지의 파생 양상

조일규 평택대학교 2000 論文集 Vol.14 No.1

이 글은 현대국어에 나타난 정의 표현 풀이씨 뒷가지의 파생 양상을 살피는 데 목적이 있다. 현대국어에서 생산성을 가지는 정의 표현 뒷가지는 '-(으)ㅂ-, -갑/겁-, -압/업-, -얍/엽-, -답-, -롭-, -스럽-' 등이 있다. '-(으)ㅂ-' 가지는 움직씨 밑말과 결합하여 정의 표현의 뜻바탕을 가진 그림씨를 파생하는 한 씨갈래 밑말 바꾸는 가지이므로 2유형 가지이다. '-갑/겁-'가지는 그림씨 밑말에만 결합하여 다시 정의 표현의 뜻바탕을 가진 그림씨를 파생하는 한씨갈래 밑말 안 바꾸는 가지이므로 1유형 가지이다. '-압/업-, -얍/엽-' 가지는 움직씨, 그림씨, 상징 어찌씨 밑말과 결합하여 정의 표현의 뜻바탕을 가진 그림씨를 파생하는 여러 씨갈래 밑말 바꾸거나 안 바꾸는 가지이므로 3유형 가지이다. '-답-' 가지는 이름씨 밑말과 결합하여 정의 표현의 뜻바탕을 가진 그림씨를 파생하는 한 씨갈래 밑말 바꾸는 가지이므로 2유형 가지이다. '-롭-' 가지는 이름씨, 그림씨, 어찌씨 밑말과 결합하여 정의 표현의 뜻바탕을 가진 그림씨를 파생하는 여러 씨갈래 밑말 바꾸거나 안 바꾸는 가지이므로 3유형 가지이다. '-스럽-' 가지는 이름씨, 어찌씨 밑말과 결합하여 정의 표현의 뜻바탕을 가진 그림씨를 파생하는 여러 씨갈래 밑말 바꾸는 가지이므로 4유형 가지이다.

남명 시에서의 선비 상(2)자연과의 조화 : 텍스트 언어학적 분석을 바탕으로 Harmony with the Nature

曺逸圭 慶尙大學校 南冥學硏究所 2002 남명학연구 Vol.14 No.-

This paper was written in search for the true classical scholar whom Nammyoung think is preferable. In accordance with the method of the Text-linguistics, described cohesion, the author analyzed the situationality, intertextuality, and informativity which were shown in Nammyoun's poems, and the results were classified into ① situation analysis, ② coherence, ③ the diagram of the synthetical structure, and ④ translation of the poems. The contents were arranged into two parts : ① the desertion of human desires and ② the harmony with the nature and the pleasure of hermit life. The poems and the analysed contents were like these: The themes of 'the desertion of human desires' and 'the harmony with the nature and the pleasure of hermit life' are different, but they are of the same category. This is because the heavenly morals is conserved when the human desires are abandoned, and the harmony with the nature and the pleasure of human morality can be obtained when the heavenly morals are conserved. Nammyong worried for the classical scholars not to cut off the human desire and to flatter themselves in search for the bureaucratic office. He said, if he became dirty because of the human desires, "he would instantly cut open the stomach, take out the dirty things, and flow down them into the river." And also he tried to put these beliefs into practice. He always carried with himself the letters of 'Piety(敬) and Righteousness(義)', and tried to be pious internally and to be righteous externally. And so Nammyong could succeed in obtaining the harmony with the nature, and could enjoy the pleasure of hermit life.