Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

Corrosion and Oxidation Resistance Behaviors of Ta-Containing Low Alloying Zirconium

Il‑Hyun Kim,Yang‑Il Jung,Byoung‑Kwon Choi,Hyun‑Gil Kim,Jae‑Il Jang 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.8

Zirconium alloys are widely used to fabricate nuclear fuel claddings, and thus is desirable to improve the resistance of suchalloys to corrosion and structural instability. In this study, Ta was used as an alloying element to improve the corrosion andoxidation resistance of zirconium alloys. The model alloy (TaZL) contained 0.03 wt% Ta and other elements with a proportionof less than 1 wt% in total (0.1 wt% Nb, 0.4 wt% Fe, 0.2 wt% Cr) in a zirconium base. The corrosion test involving pressurizedwater at 360 °C and oxidation test involving steam at 1200 °C indicated that TaZL exhibited the lowest weight gains amongthose of compared conventional and advanced Zr alloys. The corrosion and oxidation resistances of TaZL were respectivelyimproved by 4 and 1.5 times compared to the corresponding values of Zircaloy-4. The microstructures of the oxide formedon TaZL were columnar along the oxide growth direction and did not change from columnar to equiaxed, which resulted inthe high resistance of the alloy to corrosion and oxidation.

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>

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

Bae, Won-Jung,Park, Jae Suh,Kang, Soo-Kyung,Kwon, Il-Keun,Kim, Eun-Cheol MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.6

<P>The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (<I>SASP</I>) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.</P>

桑黃 물추출물이 LPS로 유도된 Raw 264.7 cell에서의 TNF-α, IL-1β, IL-6 및 Nitric Oxide production에 미치는 영향

김상찬(Sang Chan Kim),정연숙(Youn Suk Jung),이재령(Jae Ryung Lee),김영우(Young Woo Kim),변부형(Boo Hyeong Byun),권택규(Teag Kyu Kwon),서성일(Seong Il Suh),변성희(Sung Hui Byun),권영규(Young Kyu Kwon) 한의병리학회 2004 동의생리병리학회지 Vol.18 No.3

Helicobacter pyloir 양성 소화성 궤양에서 lansoprazole 포함 삼제요법의 제균율 및 제균판정에 있어서 요소호기검사의 유용성

정혜경,곽재진,유민아,배기선,권정미,이종수,김도영,문일환 대한감염학회 2003 감염과 화학요법 Vol.35 No.3

목적 : 본 연구는 Helicobacter pylori (이하 H. polyri) 양성인 소화성 궤양 환자에서 lansoprazole 포함 삼제요법의 제균율을 알아보고, 제균 치료 후 제균 판정에 있어서 요소 호기 검사(Urea breath test, 이하 UBT) 및 신속요소분해(rapid urease test, 이하 RUT test)와의 일치율에 대하여 알아보고자 하였다. 방법 : 상부위장관내시경 검사에서 H. polyri 양성인 소화성 궤양환자에서 lansoprazole 60㎎+amoxicillin 2g+clarithromycin 1g의 약제를 2회 분복하여 1주간 복용하는 삼제요법을 실시하였다. 최소 4주후 추적 상부위장관내시경을 실시하였고, 전정부와 체부에서 각각 RUT를 실시하였으며 UBT(5분, 20분)를 시행하였다. 결과 : 대상환자는 총 46명으로 남자 34명(48±13세), 여자 12명(53±14세)이었다. LAC 삼제요법의 제균율은 40/46명(87.0%)이었고, 궤양의 치유율도 42/46명(91.3%)이었다. RUT와 20분 UBT 결과가 모두 음성이었던 경우는 41예, 모두 양성이었던 경우는 4예로 RUT와 UBT는 97.8% (45/46)의 일치율을 보였고, 1예는 UBT는 음성이었으나 체부에서 시행한 RUT가 양성이었다. 5분 UBT 검사가 양성이었던 예는 14/34 (41.2%) 이었고, 이 14예 중 12예(85.7%)는 20분 UBT 검사 음성, RUT 음성이었다. 결론 : Lansoprazole과 amoxicillin, clarithromycin 1주일 병합요법은 H. polyri 양성인 소화성 궤양 환자에서 87.0%의 제균율을 나타내어 우수한 효과를 보였고, 요소호기검사는 제균 치료 후 제균 판정에 유용한 비침습적인 방법임을 확인할 수 있었다. Background : There are only a few studies on Helicobacter pylori (H. pylori) for its eradication rates of lansoprazole-based triple therapy in Korea, and the results are controversial. Therefore, we undertook to investigate the eradication rate of lansoprazole-based triple therapy, and compare the concordance rate of urea breath test (UBT) and rapid urease test (RUT) in evaluating H. pylori eradication. Methods : Patients with acute peptic ulcer who were H. pylori-positive were recruited by prospective, consecutive manner. They received lansoprazole 30 ㎎ b.d., amoxicillin 1 g b.d. and clarithromycin 500 ㎎ b.d. for 1 week. Upper endoscopy was performed after 4 weeks to check for ulcer healing, and UBT and RUT were performed to evaluate H. pylori eradication status. Results : A total of 46 patients were recruited, and they were all compliant. H. pylori eradication rate was 87.0% (40/46) and ulcer healing rate was 91.3% (42/46). Forty one patients showed negative in both UBT and RUT, and 4 patients revealed positive in both tests, therefore, the concordance rate of UBT and RUT was 97.8% (45/46). Conclusion : Our study showed that 1-week lansoprazole-based triple therapy was effective in H. pylori eradication and ulcer healing. UBT can be an effective, noninvasive method for evaluating H. pylori status after H. pylori eradication.

유육종증 3례

권건영,장은숙,주일,김정식,전영준,손수인 啓明大學校 醫科大學 1990 계명의대학술지 Vol.9 No.3

Sarcoidosis is a multisystem granulomatous disease of unknown cause, characterized by enhanced cellular immune process at the sites of involvement. Three Cases of sarcoidosis involving vilateral hilar lymph nodes, skin and lungs were presented. Each case was confirmed by characteristic non-caseating granuloma in biopsied thoracic lymph nodes and skin. They had abonormal pulmonary function test, elevated serum angiotensin converting enzyme, hilar and mediastinal lymphadenopathy and compatible clinincal features of sarcoidosis.

박막 크로멜-알루멜 열전퇴형 교류-직류 변환기

정인식,김호운,김진섭,이정희,이종현,신장규,박세일,권성원 경북대학교 센서기술연구소 1998 센서技術學術大會論文集 Vol.9 No.1

A planar chromel-alumel multijunction ac-dc converter was fabricated on a LPCVD Si_(3)N_(4)/SiO_(2)/Si_(3)N_(4)-diaphragm, prepared by silicon bulk micromachining, which thermally isolated a bifilar evanohm-heater and the hot junctions of a chromel-alumel thermopile from the silicon substrate. The voltage responsivity, the ac-dc transfer error, and the fluctuation of the output thermoelectric voltage of the converter were investigated. The respective voltage responsivities in air and in a vacuum of the converter were about 3.16 mV/mW and 9.41 mV/mW. The ac-dc voltage and the current transfer errors in air were about ±1.5 ppm and ±0.7 ppm in a frequency range from 10 Hz to 10 kHz, respectively. The fluctuation of the output thermoelectric voltage from 5 seconds to 120 seconds after preheating in air for 5 seconds was about 0.06 % for a heater input of dc 1 V.

痺의 原因에 대한 文獻的 考察

黃紅日,權貞南,金瑩均 동의대학교 한의학연구소 1997 동의한의연구 Vol.1 No.-

Throuth the bibliographical study upon the cause of Bi(痺), next conclusion have been obtained. 1. Insufficiency of Ki-blood(氣血不足) due to weakness of body, and infirmity of nutrient and defensive Ki(營衛不固) were the main endogenous cause of Bi(痺). 2. The exdogenous cause of Bi(痺) were wind evil(風), coldness(寒), and dumpness (濕) which arise from conditions of weather and living circumstance. 3. The other cause of Bi(痺) were stagnation of turbid phlegm and stasis of blood (痰濁瘀血) which flow into viscer and joints along meridian. 4. The various name of Bi(痺) which has been used with the changes of epoch, that is, Baek-Ho(白虎), Yeok-Jeol(歷節), Tong-Pung(痛風) can be concluded in Bi(痺) on a point of view of the same symtoms and causes.

진행성 비호지킨 림프종 환자에서 ICE 구제 요법에 의한 조혈모세포 가동화 후 자가 말초혈액 조혈모세포이식

이제중,이병환,김여경,변정래,이일권,박무림,정익주,김형준 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.1

연구배경: 비호지킨 림프종에서 자가 말초혈액 조혈모세포이식술이 폭넓게 이용됨으로 인해서, 높은 치료효과뿐만 아니라 조혈모세포의 가동화 효율이 높은 구제 요법이 요구되었다. 방법: 본 연구에서는 진행성 비호지킨 림프종에서 ICE 요법을 이용하여 조혈모세포를 가동화시킨 후 자가 말초혈액 조혈모세포이식이 시행하였던 환자를 후향적으로 분석하였다. 결과: 대상 환자의 중앙 연령은 38세(범위, 16~61)였으며, ICE 요법은 환자당 4주기(범위, 1~6주기)가 투여되었고, 투여 간격은 중앙값이 24일(범위, 16~36일)이었다. 고위험도 관해군을 제외한 13예의 환자 중 완전반응은 7예(53.8%), 부분반응은 4예(30.8%), 진행성질환은 2예(15.4%)를 보였다. 치료에 따른 3~4등급의 혈액학적 독성은 중성구감소증이 13예(81.3%), 혈소판감소증이 7예(42.8%)에서 관찰되었다. 조혈모세포 채집은 ICE 요법 후 중앙값이 12일(범위, 6~20일)에 시행되었고, 각 ICE 요법당 채집한 단핵구치는 중앙값이 5.75× 10^(8)/체중, CD34^(+) 세포는 중앙값이 1.25× 10^(6)/체중, CFU-GM치는 중앙값이 1.19× 10^(5)/체중이었다. 조혈모세포이식은 11예에서 시행되었고, 중앙 추적기간 401일에 평가한 2년 전체생존율은 70.1±14.7%, 1년 및 2년 무사건생존율은 각각 60.7±15.4%와 32.3±17.1%를 보였다. 결론: ICE 요법은 재발성/불응성 비호지킨 림프종 환자에서 높은 치료 반응률과 만족할 만한 조혈모세포 가동화를 보여 주었지만, 치료에 대한 순응도가 낮아서 투여 간격이 연장되는 문제점을 안고 있어서, 우리나라 환자의 실정에 적합한 구제요법에 대한 연구가 필요할 것으로 생각된다. Background: Due to the extensive application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT), a salvage chemotherapeutic regimen with high response rate as well as effective capacity of PBSC mobilization is needed in non-Hodgkin's lymphoma (NHL). Methods: We analyzed the applicability of ICE (ifosphamide, carboplatin, and etoposide) regimen in NHL patients who underewent autologous PBSCT. Results: The median age was 38 years (range, 16~61 years), the patients received median 4 cycles (range, 1~6 cycles) of ICE regimen, and the median interval between each chemotherapeutic cycle was 24 days (range, 16~36 days). There were 7 (53.8%) complete responses, 4 (30.8%) partial responses, and 2 (15.4%) progressive diseases after ICE regimen. Toxicity included grade 3/4 neutropenia and throm bocytopenia in 13 (81.3%) and 7 (42.8%) patients, respectively. PBSC collection began on median day 12 (range, 6~20 days) after ICE therapy. The median number of mononuclear cells, CD34+ cells, and CFU-GM was 5.75× 10^(8)/kg, 1.25× 10^(6)/kg, and 1.19× 10^(5)/kg, respectively. With a median follow- up of 401 days, the patients who underwent autologous PBSCT had overall survival with 70.1±14.7% at 2 year and event free survival with 60.7±15.4% and 32.3±17.1% at 1 year and 2 years, respectively. Conclusion: ICE chemotherapy is an effective cytoreduction and mobilization regimen in patients with NHL, but profound myelosuppression with delayed recovery might pose difficulties in applying for Korean patients. Further evaluation for appropriate salvage regimens in Korean patients should be needed.