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>

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.

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.

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.

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

기계적 합금화에 의해 제조된 고규소 Al-Si 합금 나노 결정의 특성

이정일,김일호,홍태환,어순철,양계준,석현광,한만갑,최국선,김준수 대한금속재료학회 2003 대한금속·재료학회지 Vol.41 No.7

High silicon Al-Si alloys with nanocrystalline structures have been produced by mechanical alloying process. Microstructural changes of the Al-Si alloys were investigated by scanning electron microscopy and the transmission electron microscopy. X-ray diffraction analysis was also made to characterize the lattice constant, crystallite size and misfit strain. It was found that the effective milling time by attrition milling was about 12hours for Al-70 wt%Si alloy system. The Al and Si crystallites were reduced to about 30 nm and 70 nm, respectively, by the mechanical alloying for more than 12hours. The misfit strains increased with milling time UD to 240 hours, and saturated to 5.73×10^(-3) for Al and Si crystallites, respectively.

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.

정상인에서 도플러 초음파술을 이용하여 측정한 니트로글리세린 투여후 두개내 혈류속도의 변화

박일(Il Park),장경식(Kyoung Sig Chang),안기완(Gi Wan An),최연수(Yeon Soo Choi),국기용(Ki Yong Kook),홍순표(Soon Pyo Hong) 대한내과학회 1995 대한내과학회지 Vol.48 No.4

N/A Objectives: With advances in transcranial ultrasound technology, transcranial color-code Doppler ultrasonography provides the anatomical location of basal transcranial vessel and their blood flow. To study of changes of cerebral blood flow, we measured continuously the blood flow velocity of middle cerebral artery by transcranial Doppler(2.5MHz) before and after sublingual administration of 0.6mg. nitroglycerin in twenty healthy young persons. Methods: Pulse rate and systolic and diastolic blood pressure and velocity of percussion(P), tidal (T) and dicrotic(Dc) wave, and diastole(Ds), velocity time integral(VTI), mean velocity(V), pulsatility index(PI) were measured. Results: Heart rate was increased, and systolic blood pressure was decreased significantly two minutes after administration of nitroglycerin. Diameter of outer margin of color Doppler spectrum was increased, and P, T, Ds, VTI and V were decreased significantly after two minutes. PI was increased significantly after two minutes, but returned to baseline level soon. Conclusion: We concluded that dilatation and decreased blood flow velocity of middle cerebral artery were resulted by nitroglycerin.