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>

Increased serum interleukin-10 level in Kawasaki disease

Kim, Dong Soo,Lee, Hong Kyu,Noh, Geun Woong,Lee, Soon Il,Lee, Ki Young Yonsei University, College of Medicine 1996 Yonsei medical journal Vol.37 No.2

A novel, topical, nonsteroidal, TRPV1 antagonist, PAC-14028 cream improves skin barrier function and exerts anti-inflammatory action through modulating epidermal differentiation markers and suppressing Th2 cytokines in atopic dermatitis

Lee, Ji-Hae,Choi, Chang Soon,Bae, Il-Hong,Choi, Jin Kyu,Park, Young-Ho,Park, Miyoung Elsevier 2018 JOURNAL OF DERMATOLOGICAL SCIENCE Vol.91 No.2

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown.</P> <P><B>Objective</B></P> <P>Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD.</P> <P><B>Methods</B></P> <P>AD-like dermatitis was induced in hairless mice by repeated oxazolone (Ox) challenges to hairless mice. The functional studies concerning skin barrier function, anti-inflammatory action, and molecular mechanism by TRPV1 antagonism were conducted by histopathological assays, ELISA, qPCR, western blotting, and skin blood flow measurement.</P> <P><B>Results</B></P> <P>Topically administered TRPV1 antagonist, PAC-14028 (Asivatrep: C<SUB>21</SUB>H<SUB>22</SUB>F<SUB>5</SUB>N<SUB>3</SUB>O<SUB>3</SUB>S), improved AD-like dermatitis and skin barrier functions, and restored the expression of epidermal differentiation markers. In addition, the PAC-14028 cream significantly inhibited cutaneous inflammation by decreasing the expression of serum IgE, and the epidermal expression of IL-4, and IL-13 in Ox-AD mice. These results may provide a novel insight into the molecular mechanism of PAC-14028 cream involved in anti-inflammatory effects and skin barrier functions by suppressing the multiple signaling pathways including IL-4/-13-mediated activation of JAK/STAT, TRPV1, and neuropeptides.</P> <P><B>Conclusion</B></P> <P>PAC-14028 cream can be a potential therapeutic tool for the treatment of chronic inflammation and disrupted barrier function in patients with AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PAC-14028 1% topical cream is an anti-inflammatory, non-steroidal TRPV1 antagonist. </LI> <LI> PAC-14028 cream treatment reduced AD-like symptoms and improved skin barrier functions in Ox-induced <I>in vivo</I> murine model. </LI> <LI> PAC-14028 suppressed the signaling pathways including IL-4/-13 mediated activation of JAK/STAT, TRPV1, and neuropeptides. </LI> </UL> </P>

木材의 硬度에 關한 硏究

洪淳一,李元用 江源大學校 林科大學 森林科學硏究所 1992 Journal of Forest Science Vol.8 No.-

This study was performed to investigate the hardness of wood related to the wood surface, sap and heartwood, early and latewood, specific gravity, annual ring width and moisture content on major Korean tree species such as Pinus koraiensis, Abies holophylla, Larix leptolepis and Quercus valiabilis. The results were summarized as follows: 1. The arithmetic mean values of wood hardness on cross section were respectively 8.0 ㎏/㎟ on Quercus valiabilis, 7.4 ㎏/㎟ on Larix leptolepis, 5.1 ㎏/㎟ on Pinus koraiensis and 4.7 ㎏/㎟ on Abies hollophylla. 2. Generally hardness of wood on cross section was greater than the others and the proportion of cross section hardness to radial was respectively 2.8 on Quercus valiabilis, 2.6 on Larix leptolepis, 3.8 on Pinus koraiensis, and 4.1 on Abies holophylla and that proportion was tend to be decrease as specific gravity increased. 3. It was recognized that the hardness of sap and heartwood was different from each of the tree species and generally heartwood hardness was somewhat greater than sapwood. 4. Generally latewood hardness with in a ring was greater than earlywood and the proportion of earlywood hardness to latewood decreased as specific gravity increased. 5. The relations between hardness of wood and specific gravity show a high positive correlation on all sample tree species. 6. The values of hardness decreased with increasing annual ring width. 7. Hardness of wood on Abies holophylla was greatest in oven dried wood and it was decreased as moisture content increased, but not changed with moisture content abve F.S.P.. The proportion of oven dried wood hardness to green are respectively 3.0 on cross, 2.4 on radial and 1.9 on tangential section.

지역사회 정신의학 전공의 교육과정 실태조사

홍진표,황순찬,이영문,이선형,신나리,이종일,박종익,장동원,정인원 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.1

Objectives : There is a increasing need to recruit and retain more psychiatrists who can plan and implement organized programs to work with chronic mentally ill patients in community settings. The aim of study is to discover what training is currently in place to prepare psychiatrist for work in "community" or "public" settings. Methods : Survey questionnaires were mailed to 85 residency training directors and 10 leaders of community mental health in 2005. Response rate was 75%. Results : Academic seminar about community mental health were not administered to residents in 63% of training hospitals. Forty one out of 64 training hospitals had community mental health rotation programs, Community mental health center (50%) and day hospital (36%) were the most common type of programs. Few general hospital had affiliation with community mental health programs. The amount of time for clinical rotation varied from less than three months part time to 6 months fulltime, with most frequent form of one day per week for three month in second or third year of psychiatry residents. Conclusion : Further steps are needed to improve residency training curricula and to encourage well qualified psychiatrist to choose careers in community psychiatry.

KLEINE-LEVIN 증후군 2례

홍순형,정인과,김순범,한선호,곽동일,이병윤 大韓神經精神醫學會 1981 신경정신의학 Vol.20 No.2

The Kleine-Levin syndrome is composed of recurring episodes of sleepiness lasting days, associated with excessive appetite and often with abnormal behavior. The authors reported two cases of the Kleine-Levin syndrome. The results were as follows: 1. They were adolescent male patients. 2. The onsets were predisposed by psychological stresses of school examinations. 3. Their electroencephalograms revealed abnormal findings only during episodes of hypersomnolence. 4. One of them was improved by treatment with imipramine and lithium.

약물치료에 가역적 회복을 보인 갈색세포종에 동반된 확장성 심근증 1례

홍숙경,최현,이승철,천경일,김영철,한재룡,김미숙,정경태,박순창 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.2

비안와대뇌형 모균증 치험 3례

문영일,김종남,홍순관,이지애,정옥경,김문정 梨花女子大學校 醫科大學 醫科學硏究所 1997 EMJ (Ewha medical journal) Vol.20 No.3

Rhinocerebral mucormycosis is a well-described fulminant fungal infection that typically presents in a rapidly fulminant manner. This condition is more likely to occur among patient with diabetes mellitus, malignant tumors, who have long-term steroid treatment, or who suffer from some debilitating diseases. We report 3 cases of rhinoorbitocerebral mucormycosis, all suffered from diabetes mellitus. In all 3 cases, endoscopic sinus surgery was done and the antifungal agent(amphotericin B) was administered intravenously, and two patients died. One survivor who had focal extension of paranasal sinus and orbit, required one surgical intervention without orbital exenteration and he is alive without recurrence disease. The severity of the disease is probably dependent upon the gost resistance to the invasion of phycomycetes. Early diagnosis and immediate, effective treatment are the key for cure of the disease.

외상에 의한 지연성 뇌경색 2예 : Case Reports

김수일,김헌주,한용표,홍순기,허철 대한신경외과학회 1989 Journal of Korean neurosurgical society Vol.18 No.5

Delayed traumatic cerebral infarction appears to occur more frequently than previously expected. We have experienced two cases of this clinical entity whose initial neurological condition were good except headache and/or mental confusion. However, their initial Brain CT scans showed no specific abnormalities. The detailed neurological examination and follow up Brain CT scans were prerequisite choices of strategy against this type of lesion. However, additional studies regarding intracranial pressure(ICP), cerebral blood flow(CBF), multimodality evoked potential(MMEP) and magnetic resonance imaging(MRI) should be considered as an alternative armamentarium for further elucidation of vascular insults to already injured brain.

젖소 말초혈액 림프구로부터 소백혈병 바이러스 배양 및 전자현미경적 관찰

윤순식,박중원,변재원,강문일,유한상,한홍율 韓國電子顯微鏡學會 2005 Applied microscopy Vol.35 No.1

국내 젖소의 54.2%가 BLV에 감염되어 있지만 현재까지 국내에서는 소백혈병 바이러스 (BLV) 입자를 확인한 연구 보고가 없기 때문에 BLV 항체 양성 소의 말초혈액림프구를 배양, BLV를 발현시켜 전자현미경으로 바이러스 입자를 검출하였고 배양조건에 따른 바이러스 발현율 및 발현 시간을 비교하였다. 검사 결과 전형적인 C-형 바이러스를 확인할 수 있었으며 BLV 단크론 항체를 이용한 면역염색결과 BLV 항원 양성으로 확인되었다. BLV 는 대부분 세포 외부에 분포하고 있었으며 세포질 막에서 생성, 발아되어 나오는 것도 관찰되었다. 전체 바이러스의 크기는 90~100 nm였으며 nucleocapsid는 40~60nm였다. 소태아혈청 (FBS)과 T- 및 B-림프구 분열촉진물질(mitogen)을 각각 첨가하여 배양한 결과 두 군 모두에서 BLV 발현이 확인되었다. Lipopolysaccharide 첨가군은 배양 12시간, Conconavalin A 첨가군은 배양 24시간에 각각 림프구의 10%에서 바이러스가 관찰되었다. 또한 FBS만 첨가한 군과 FBS와 mitogen을 모두 첨가하지 않은 군에서도 관찰되었으나 바이러스의 수는 적었다. 본 연구에서 확립된 BLV 배양 기법을 활용하면 BLV에 감염된 소 중 바이러스를 발현하는 소, 즉 전파능이 있는 개체를 찾아내어 우선적으로 도태할 수 있기 때문에 BLV 감염으로 인한 피해를 막는데 효과적으로 이용될 수 있을 것으로 사료된다. Many studies have been performed on the bovine leukemia virus (BLV) since bovine leukosis had been reported in 1968 in Korea. However, there was no report on the ultrastructural examination of BLV. An attempt to detect C-type viral particles in the cultured peripheral blood lymphocytes of Holstein-Friesian dairy cattle, was made to determine whether in vitro viral expression might be used as a reliable method to identify the cow which is likely to transmit BLV. In transmission electron microscopic (TEM) examination, the virus particles were found predominantly outside of the lymphocytes even though a few particles were also observed within the membrane bound cytoplasmic vacuoles. All of them were C-type particles consisting of a central, electron-dense core separated by a clear area from a limiting envelope with a unit membrane structure. Virus particles were easily detected in the lymphocyte which was cultured with medium supplemented with either T-lymphocyte mitogen (conconavalin A) or B-lymphocyte mitogen (lipopolysaccharide). Identical viral particles, although fewer, were also consistently present in the lymphocytes cultured with medium which was containing foetal bovine serum (FBS) only and which was containing neither FBS or mitogen. By contrast, no virus particle was detected in extensive examination of lymphocytes before culture. In conclusion, the BLV cultivation and detection methods established in this study could be used as a tool to identify and eliminate the cattle which can transmit the BLV.