PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression

Yun-Jeong Choe,고경원,Hyein Lee,이선영,Byung-Chul Kim,Ho-Shik Kim,Ho-Shik Kim 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.4

Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.

Effects of Herbal Extracts Used in Oriental Medicines on Heme Oxygenase-1 Expression

Jeong, Gil-Saeng,Oh, Seung-Hwan,Kang, Dae-Gill,Lee, Ho-Sub,Kim, Youn-Chul The Physiological Society of Korean Medicine and T 2006 동의생리병리학회지 Vol.20 No.5

Effects of twenty-three aqueous herbal extracts used in oriental medicines on heme oxygenase (HO)-1 expression were estimated in a mouse hippocampal cell line, HT22. HO-1 is one of the cytoprotective enzymes activated various stimuli, and Western blot analysis was used for evaluated HO-1 expression. Six aqueous extracts such as Rhei Rhizoma, Paeoniae Radix, Uncariae Ramulus et Uncus, Theae Folium, Prunellae Spica, and Coptidis Rhizoma significantly increased HO-1 expression in HT22 cells at the concentration of 300 ${\mu}$g/ml. In Addition, four aqueous extracts including Eucommiae Cortex, Moutan Cortex Radicis, Ginseng Radix Rubra, and Scutellariae Radix moderately increased HO-1 expression. These results would be usefulfor the isolation and identification of their neuroprotective principles.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

작업관련성 수근관증후근 감시체계

정우철,권호장,하미나,노상철,권범선,현정근,이성재,이종민,권정이,김준성,백남종,이호,이경우,이삼규 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

목적: 작업관련 근골격계질환은 중요한 직업관련성 질환 중의 하나이고 작업관련 수근관증후군은 이러한 작업관련 근골격계질환 중에서도 많은 부분을 차지한다. 이 연구는 작업관련 수근관증후군의 역학적 특성에 대해 알아보고자 수행되었다. 방법: 본 연구에서는 '수근관증후군 감시체계'를 통해 2000년 6월부터 2003년 2월까지 보고 된 672례의 수근관증후군 사례를 분석하였다. 직업력이 확인된 314명을 대상으로는 직업 및 작업내용에 따라 작업관련성 수근관증후군의 비율이 어떻게 달라지는지를 분석함으로써 수근관증후군 위험요인을 조사하였다. 결과: 직업력이 확인된 314명의 환자 중 작업 관련성이 의심되는 사람은 228명 (72.6%) 이었다. 직업별로는 '단순노무종사자', '농림어업숙련자', '서비스종사자' 등에서 작업관련 수근관증후군의 비율이 여성에서 유의하게 높게 나타났으나 연령, 비만도 지수, 과거병력 등에 따른 차이는 관찰되지 않았다. 주관적 증상 중에 '손을 많이 사용한 후 심해진다'와 '손을 털면 덜해진다'라는 항목을 작업관련성 수근관증후군 환자에서 더 많이 호소하였고 다른 증상은 별다른 차이를 보이지 않았다. 작업관련성 수근관증후군 환자가 비교적 많이 노출되는 작업은 '지나치게 손을 뻗쳐서 하는 일', '손을 불편한자세로 유지하는 일' 등이었다. 결론: 전체 수근관증후군 중 작업관련성이 있다는 비율이 매우 높은 것을 확인할 수 있었다. 수근관증후군 감시체계가 작업관련성 수근관증후군의 여러 특성을 밝히는데 매우 효과적인 것으로 나타났으나 현재까지는 중재 대상을 구체적으로 특정하기에는 한계가 있다. Objectives: Carpal tunnel syndrome (CTS) is one of the most important work related musculo-skeletal diseases in Korea. However, there are few epidemiologic studies on the work-related CTS (WR-CTS). This study aimed to investigate the epidemiologic characteristics of WR-CTS in Korea. Methods: Data obtained from the "CTS Surveillance System". Physician case-reports in the surveillance were used to document patterns of WR-CTS by age, gender, occupation, sign, symptom, working history. Results: Six hundred and seventy-two cases of WR-CTS were ascertained of which 3 14 with complete information on occupational history were analyzed. It has been estimated that as many as 72% of' all CTS cases are work-related. The highest proportion of WR-CTS was observed in 'elementary occupation workers', followed by 'skilled agricultural, forestry and fishery worker'. The distributions of WR-CTS cases were similar with respect to age, obesity, and past medical history. The proportion of WR-CTS was higher in females. There was no significant difference in physical examination findings between WR-CTS and non WR-CTS cases. Repetitive work and the inappropriate hand posture seemed to be the risks for WR-CTS. Conclusion: WR-CTS is a significant public health problem. The CTS surveillance system is quite useful to elucidate the characteristics of WR-CTS, but it remains of limited use in targeting specific industries and occupations for intervention.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

Sauchinone Suppresses Pro-inflammatory Mediators by Inducing Heme Oxygenase-1 in RAW264.7 Macrophages

Li, Bin,Lee, Dong-Sung,Choi, Hyun-Gyu,Kim, Kyoung-Su,Kang, Dae-Gil,Lee, Ho-Sub,Jeong, Gil-Saeng,Kim, Youn-Chul Pharmaceutical Society of Japan 2011 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.34 No.10

<P>Sauchinone, a biologically active lignan isolated from the roots of <I>Saururus chinensis</I> (L<SMALL>OUR</SMALL>.) B<SMALL>AILL</SMALL>. (Saururaceae), is reported to exert a variety of biological activities, such as hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone in suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-derived prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) and iNOS-derived nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. Present study also demonstrates the effects of sauchinone in inducing heme oxygenase-1 (HO-1) expression and an increase in heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of sauchinone on LPS-induced PGE<SUB>2</SUB>, NO, tumor necrosis factor-α (TNF-α) and interlukine-1β (IL-1β) production were partially reversed by the HO-1 inhibitor Tin protoporphyrin was also seen in this study. In addition, we found that treatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) reduced sauchinone-induced HO-1 expression. Sauchinone also increased ERK phosphorylation. These results suggest that sauchinone inhibits pro-inflammatory mediators through expression of anti-inflammatory HO-1 <I>via</I> ERK pathway.</P>

타이밍 오류 검출회로의 설계

정한철,곽철호,김정범 강원대학교 정보통신연구소 2002 정보통신논문지 Vol.6 No.-

Error control is one of major concerns in many computer systems. Experience shows that most malfunctions during system operation are caused by transient faults, which often mean abnormal signal delays that may result in violations of circuit element timing constraints. This paper presents a novel CMOS-based concurrent timing error detector that makes a flip-flop (or other timing-sensitive circuit element) to sense and then signal whether its data has been potentially corrupted or not by a setup or hold timing violation. Designed circuit performs a quiescent supply current evaluation to determine timing violation from the input changes in relation to a clock edge. If the input is too close to the clock time, the resulting switching transient current in the detection circuit exceeds a reference threshold at the instant of the clock transition and an error is flagged. The simulation results in this paper shows that designed circuit can be used to detect setup and hold time violations effectively in clocked circuit element.

강체아령분자액체의 상태방정식

정기주,배영호,최철규 충남대학교 자연과학연구소 1988 忠南科學硏究誌 Vol.15 No.2

The equation of state of hard dumbbell molecular liquids is studied by using the equivalent hard sphere as the reference system on one hand and the equivalent hard disphere system on the other hand. For the equivalent hard sphere liquid, the equation of state is calculated by the well known Carnahan-Starling fitting function. And the Wertheim's formula recently proposed is used to obtain the equation of state of the hard disphere system. It is then shown that the hard disphere system is the better approximation to the hard dumbbell liquids, by comparing with the molecular dynamic simulation data, especially for the greater eccentricity of the molecule and for the higher packing fraction.

이중중합 수복재의 시간경과에 따른 중합도 변화

정태성,김신,양철호 大韓小兒齒科學會 1999 大韓小兒齒科學會誌 Vol.26 No.3

심미적 수복 재료인 복합 레진과 글래스 아이오노머 시멘트는 중합방식에 따라 화학중합형, 광중합형, 그리고 이 두 가지 중합방식을 겸비한 이중중합형으로 분류할 수 있다. 화학중합형과 광중합형에 대해서는 지금까지 다수의 보고가 있었으나, 충전용 복합 레진의 경우 이들과 이중중합형을 비교한 예는 아직 찾기 힘든 실정이었으므로,이러한 관점에서의 연구가 필요할 것으로 사료되었다. 이 연구에서는 이중중합 수복재가 단일중합방식에 비해 어떠한 특성을 보이는지를 탐구하고자 하였다. 사용된 재료는 광중합형 복합 레진인 Veridonfil-Photo와 이중중합형인 Bis-core,이중중합형인 글래스 아이오노머 시멘트인 Fuji Ⅱ LC와 화합중합형인 Ketac-fil을 사용하였다. 가로 30mm,세로 30mm 높이 1mm와 3mm인 두 종류의 아크릴릭 몰드 중앙에 직경 7mm의 hole을 형성하여, 여기에 4종의 수복재를 충전하였다. 충전 직후부터 시작하여 24시간 경과시까지 일정 시간 간격으로 표면, 1mm,3mm깊이에서의 경도를 미세경도계(Shimadzu Micro Hardness Tester HMV-2000,Shimadzu Co.Japan)로 측정하였다. 측정치를 통계처리하여 얻은 결과는 다음과 같다. 1.4종의 수복재 모두에서,중합직후에 비해 24시간 경과후의 미세경도가 증가되었다. 2.중합 직후부터 24시간 경과후의 미세경도를 측정한 결과, Ketac-fil을 제외한 나머지 수복재에서는 각 깊이간 경도의 차이가 있었다. 3.각 수복재의 최종중합에 도달하는 시간을 조사한 결과, 이중중합형이 3mm의 깊이에서 광중합형이나 화중합형에 비해 중합이 더 오래 지속된 것으로 나타났다. 이상의 결과에서 조사광이 충분히 도달하지 못하여 중합이 현저히 떨어지는 수복재의 심부에도 이중중합방식을 사용할 경우에는 지속적인 중합반응이 일어나 중합도가 증가하는 것으로 나타났다. For the purpose of elucidating the polymerization modes of dual-cure restorative materials and comparing them with single-cure restorative materials,a study was performed on the light-cured composite resin,dual-cure composite resin,dual-cure glass innomer cement. By measuring the microhardness of each material at 0mm,1mm and 3mm depth during initial 24 hours with predetermined interval,the state of polymerization and degree of conversion was indirectly evaluated for each material,and obtained results are as follow: 1.All of four materials tested showed significant increase in microhardness after 24hrs compared with just after curing starts. 2.In all materials except Ketac-fil,there showed a significant difference in microhardness between each depth at each time interval. 3.In the test of lap time till final curing for each material,the polymerization process was revealed to last longer in the dual-cure type materials than in single-cure type materials at 3mm depth. Based on the results avobe,it was demonstrated with materials of dual-cure mode that the degree of conversion increase by successive curing reactions even in the deeper layers where sufficient curing light is impermeable.

운동선수 및 비운동선수들의 심박수에 관한 연구

정성호,이철희,진성호 公州大學校스포츠科學硏究所 1989 스포츠科學硏究所論文集 Vol.- No.3

The purpose of this study was to investigate the effect of work on heart rate. The subjects of this study were 6 athletes whose ahtletic careers were about 5 years and 6 nonathletes. And the items which were tested were resting heart rete, maximum heart rate, and recovery heart rate in 1, 3, 5 minute. The conclusoin were as follows ; 1. The resting heart rate of athletic group was 64.16 +/-2.22 beats/min and 74.00 +/-8.48 in nonathletic group. Therefore the resting heart of athletic group was significantly lower than that of nonathletic group. (P<.05) 2. The maxium heart rates of athletic and non athletic group were 186.167 +/-3.656 beats/min and 204.000 +/-11.313 beats/min. The maximum heart rate of athletic group was significantly lower than that of nonathletic group. (P<.01) 3. The heart rates of recovery phase were shown 136.500 +/-14.152 beats/min and 159.167 +/-9.347 beats/min, 105.333 +/-8.477 beats/min and 127.000 +/-5.366 beats/min, 102.667 +/-7.1888 beats/min and 119.500 +/-7.007 beats/min in each 1, 3, 5, minute recovery phase. The heart rate of recovery phase in ahtletic group were significantly lower than of nonathletic group in each recovery phase.