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A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130
Hong, Soon-Sun,Choi, Jung Ho,Lee, Sung Yoon,Park, Yeon-Hwa,Park, Kyung-Yeon,Lee, Joo Young,Kim, Juyoung,Gajulapati, Veeraswamy,Goo, Ja-Il,Singh, Sarbjit,Lee, Kyeong,Kim, Young-Kook,Im, So Hee,Ahn, Sun The American Association of Immunologists, Inc. 2015 JOURNAL OF IMMUNOLOGY Vol.195 No.1
<P>IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified-LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-alpha production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6R alpha, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6R alpha complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.</P>
Interleukin-2가 호산구 생존에 미치는 영향과 기전에 관한 연구
김효석 ( Hyo Seok Kim ),이영목 ( Young Mok Lee ),최영수 ( Young Soo Choi ),김경호 ( Kyung Ho Kim ),임건일 ( Geon Il Im ),문승혁 ( Jeong Sung Whan ),정성환 ( Moon Seung Hyug ),김현태 ( Hyeon Tae Kim ),어수택 ( Uh Soo Taek ),김용훈 대한결핵 및 호흡기학회 1996 Tuberculosis and Respiratory Diseases Vol.43 No.3
( Hye Min Kim ),( Jae Seung Kang ),( Jong Pil Im ),( Se Yeon Bae ),( Ye Jin Kim ),( Hang Rae Kim ),( Joo Sung Kim ),( Young Il Hwang ),( Wang Jae Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: Mucosal damage in inflammatory bowel diseases (IBDs) involves the dysfunctional immunoregulation of the gut. Among immunoregulatory factors, oxidative stress is abnormally high level in IBDs, and their destructive effects may contribute to the initiation or propagation of the disease. Vitamin C has both anti-oxidant and immunomodulatory effects. Methods: we investigated the effect of vitamin C on dextran sulfate sodium (DSS)-induced colitis in Gulo(-/-) mice which cannot synthesize vitamin C. Results: Vitamin C-insufficient Gulo(-/-) mice showed decreased survival with increased oxidative stress and more severe colitis. The production of interleukin (IL)-6 was higher, and STAT3 and Akt were more activated in DSS-treated vitamin C-insuffi cient Gulo(-/-) mice than in vitamin C-suffi cient Gulo(-/-) mice and wild-type mice. In contrast, the production of IL-22, the recruitment of NKp46(+) cells, and the activation of p38 MAPK were decreased in the vitamin C-insuffi cient Gulo(-/-) mice accompanied by decreased mucin-1 expression. Taken together, vitamin C insuffi ciency was associated with not only increased oxidative stress and IL-6 production but also decreased production of IL-22, which eventually induces severe colitis and death by DSS treatment. Conclusions: Therefore, our results suggest that vitamin C has a protective effect on DSS-induced colitis by regulating the production of cytokine and the induction of infl ammation.
환경영향평가에 있어서 보건영향평가의 방법, 절차 및 적용에 관한 연구
조일형,박재홍,김임순,한상욱 한국환경영향평가학회 2003 환경영향평가 Vol.12 No.3
Most environmental impact assessment(EIA) programs around the world require the consideration of human health impacts. Yet relatively few EM documents adequately address those impacts. This article examines how, why, and to what extent health impacts are analyzed in environmental impact assessments. This article investigates these problems and provides recommendations to improve human health impact assessment(HIA), using methods, procedures and case study. Also, a comprehensive approach for the evaluation of possible health effects in an EIA is described, illustrated with the example of Amsterdam Airport Schiphol. Unlike many EIAs, we estimated quantitatively the impact of aircraft-related pollution in terms of the number of affected people for aircraft noise annoyance, odour annoyance and hypertension. In addition, an analysis of health registry data on cardiovascular and respiratory diseases and a short survey on annoyance and risk perception were carried out.
이용근,임미경,문상은,이건일 大韓齒科器材學會 1995 대한치과재료학회지 Vol.22 No.2
The purpose of this study was to investigate the level of the radiopacity of composite resins, glass ionomers for filling and cements, and to determine the optimum level of radiopacity that is the most appropriate for the radiologic diagnosis of secondary caries. The experiments were performed in two parts. In the first part, the radiopacities of specimens of seven composite resins, two glass ionomers and four cements were measured by densitometer and those of the combined specimens were also measured. In the second part, caries was simulated by grooves of the depth of 0.5, 1.0, 1.5, 2.0mm in aluminium blocks of 4mm. thick. Specimens of 2, 4, 6mm. thick were mounted on the caries simulation block, and the differences of radiopacities between caries portion and noncaries portion were analyzed. The following results were obtained : 1. The radiopacity of dental materials at 2mm thickness displayed a wide range of radiopacity, from 1.14 to 11.70mm. aluminium equivalents. 2. Most of the cements showed significantly higher radiopacity values of 8.78 to 11.70mm. aluminium equivalents, and those of ZPC were higher than any other materials used in this study. 3. Filling materials with radiopacity similar to enamel showed a tendency to have a sufficient degree of contrast facilitate the detection of underlying recurrent caries.
신부전이 동반된 당뇨병 환자에서 발생된 침습성 모균증 : 수술과 Liposomal amphotericin B 및 GM-CSF 병합 요법에 의한 성공적인 치험 1예
이원영,오기원,임국희,장재혁,이동건,최정현,강무일,신완식,차봉연,이광우,손호영,강성구 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.4
저자들은 신부전이 동반된 당뇨병 환자에서 발생된 부비동형 모균증에 대하여 수술과 함께 liposomal amphotericin B 및 GM-CSF의 복합치료를 하여 성공적으로 치료한 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. Mucormycosis (zygomycosis) primarily affects diabetic or immunocompromised patients and typically progresses rapidly, necessitating surgical excision and antifungal therapy with amphotericin B. Large doses of amphotericin B are needed for cure, but it has the risk of causing significant renal toxicity. The recent development of liposomal amphotericin B allows antifungal therapy to be administered with potentially improved efficacy and reduced nephrotoxicity. We have experienced a case of paranasal mucormycosis successfully treated with surgery, liposomal amphotericin B and GM-CSF. A 59-year-old male suffering from diabetes mellitus for 6 years was admitted with pain at left maxillary area. He was diagnosed as mucormycosis after cytologic exam on the necrotic nasal mucosa, which showed typical hyphae. He have had diabetic nephropathy with macroproteinuria and had rapidly rising serum creatinine levels with the amphotericin B treatment: creatinine levels reverted to basal level with the use of liposomal amphotericin B. Despite surgical excision and continued antifungal therapy, his infection was not effectively controlled. Therefore, GM-CSF was administered additionally to improve phagocytic activity of leukocytes. He was finally cured after receiving a combination of aggressive surgery, liposomal amphotericin B and GM-CSF. To our knowledge, this is the first detailed clinical description of the treatment of mucormycosis with liposomal amphotericin B in Korea.
박정덕,임헌방,최병선,권일훈,이상연,강은용,홍연표,장임원 大韓産業醫學會 1999 대한직업환경의학회지 Vol.11 No.1
Cadmium(Cd) is an ubiquitous, toxic and nonessential metal which is controversial about the association with a cardiovascular disease. In this study, we investigated the reference level of Cd in myocardium in Korean general population. The level of Cd and zinc(Zn) concentration in myocardium of 252 cases of "sudden and unexpected death" autopsies (male: 172, female : 60) aged 0 to 87 years was analyzed. The concentration of Cd and Zn was determined with atomic absorption spectrophotometer(Perkin-Elmer Model 5100) by flameless and flame method, respectively. The content of Cd and Zn in myocardium showed the log-normal distribution rather than normal distribution. Geometric mean concentration of Cd was 0.19 ㎍/g wet weight in myocardium. The level of Cd in myocardium was not significantly different between male (0.18㎍/g wet weight) and female (0.22㎍/g wet weight). Geometric mean concentration of Zn in myocardium was 25.25 ㎍/g wet weight. The level of Zn between male (25.13 ㎍/g wet weight) and female (25.57㎍/g wet weight) was not different. The deposit of Cd in myocardium was age-dependent of biphasic pattern, but the Zn level by age was not significantly different. The level of Cd in myocardium was increased to the fifties of age, thereafter a leveling-off was shown. The regression model of Cd deposit in myocardium by age was predicted as the following equation: Log Heart-Cd= -1.2726 + 0.0234 ·Age -0.0002 ·Age². The maximum Cd deposit in myocardium was estimated to be 0.26 ㎍/g wet weight at the age of 58.5 in Korean general population. In addition, the total Cd burden in heart by age was predicted as a following equation: Total Cd burden in Heart= -10.165+2.891 ·Age -0.0258 ·Age². The maximum heart burden of Cd was estimated to be 70.7㎍ at age of 55.4. The positive correlation between Cd and Zn was observed in myocardium. The linear regression equation was Log Heart-Zn = 1.4195+0.0262 ·Log Heart-Cd.
( Min Kyoung Shin ),( Hong Tae Park ),( Seung Won Shin ),( Myung Hwan Jung ),( Young Bin Im ),( Hyun Eui Park ),( Yong Il Cho ),( Han Sang Yoo ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.2
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic debilitating disease affecting ruminants worldwide. In the present study, we aimed to determine the major gene networks and pathways underlying the immune response to MAP infection using whole-blood cells, as well as provide the potential transcriptional markers for identifying the status of MAP infection. We analyzed the transcriptional profiles of wholeblood cells of cattle identified and grouped according to the presence of MAP-specific antibodies and the MAP shed by them. The grouping was based on the results obtained by ELISA and PCR analyses as follows: i) Test1 group: MAP-negative results obtained by ELISA and positive results obtained by PCR; ii) Test2 group: MAP-positive results obtained by ELISA and negative results obtained by PCR; iii) Test3 group: MAP-positive results obtained by ELISA and positive results obtained by PCR; iv) uninfected control: MAP-negative results obtained both by ELISA and PCR analysis. The results showed down-regulated production and metabolism of reactive oxygen species in the Test1 group, activation of pathways related to the host-defense response against MAP (LXR/RXR activation and complement system) in the Test2 and Test3 groups, and anti-inflammatory response (activation of IL-10 signaling pathway) only in the Test3 group. Our data indicate a balanced response that serves the immune-limiting mechanism while the host-defense responses are progressing.
Efficient HgTe colloidal quantum dot-sensitized near-infrared photovoltaic cells.
Im, Sang Hyuk,Kim, Hi-jung,Kim, Sung Woo,Kim, Sang-Wook,Seok, Sang Il RSC Pub 2012 Nanoscale Vol.4 No.5
<P>We have demonstrated the successful fabrication of multiple-layer colloidal quantum dot (CQD)-sensitized near-infrared (NIR) photovoltaic (PV) cells using the solution processable HgTe CQDs and poly-3-(hexylthiophene) (P3HT) as hole-conducting polymer. The cells showed a 3.6 fold enhancement in power conversion efficiency under NIR light illumination by the post-ethanedithiol chemical treatment. The performance enhancement was mainly ascribed to the improved interfacial contact between HgTe CQDs by elimination of oleic acid as capping ligand on the surface of HgTe CQDs. In addition, the HgTe CQD-sensitized PV cells could effectively detect weak NIR light and process over 1 kHz level signals.</P>