Elevated TRAF2/6 expression in Parkinson's disease is caused by the loss of Parkin E3 ligase activity.

Chung, Ji-Yun,Park, Hee Ra,Lee, Su-Jin,Lee, Sun-Hye,Kim, Jin Sik,Jung, Youn-Sang,Hwang, Sang Hyun,Ha, Nam-Chul,Seol, Won-Gi,Lee, Jaewon,Park, Bum-Joon United States and Canadian Academy of Pathology [e 2013 Laboratory investigation Vol.93 No.6

<P>Parkinson's disease (PD) is the second leading neurodegenerative disease, and is known to be induced by environmental factors or genetic mutations. Among the verified genetic mutations of PD, Parkin, isolated from the PARK2 locus, shows an autosomal recessive inheritance pattern and is known to be an E3 ligase. However, the physiological target of Parkin and the molecular mechanism of Parkin-deficiency-induced PD have not been clearly demonstrated until now. It has recently been proposed that inflammation, suggesting as a causal factor for PD, is enhanced by Parkin deficiency. Thus, we examined the relationship between inflammation-related factors and Parkin. Here, we provide the evidence that Parkin suppresses inflammation and cytokine-induced cell death by promoting the proteasomal degradation of TRAF2/6 (TNF-α receptor-associated factor 2/6). Overexpression of Parkin can reduce the half-lives of TRAF2 and TRAF6, whereas si-Parkin can extend them. However, mutant Parkins did not alter the expression of TRAF2/6. Thus, loss of Parkin enhances sensitivity to TNF-α- or IL-1β-induced JNK activation and NF-κB activation. Indeed, si-Parkin-induced apoptosis is suppressed by the knockdown of TRAF6 or TRAF2. We also observed elevated expression levels of TRAF6 and a reduction of IκB in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model. Moreover, elevated expression levels or aggregation of TRAF6 were detected in approximately half of the human PD tissues (7/15 cases) and 2 cases, respectively. In addition, TRAF6 and Parkin expression levels show a reverse relationship in human PD tissues. Our results strongly suggest that the reduction of Parkin or overexpression of TRAF2/6 by chronic inflammation would be the reason for occurrence of PD.</P>

Max Frisch의 작품 <빈 또는 북경여행 Bin oder Die Reise nach Peking>에 나타난 동경의 문제

박충하 ( Chung Ha Park ) 한국독어독문학교육학회 1997 獨語敎育 Vol.15 No.-

양대박(梁大樸)의 「청계동도(靑溪洞圖)」 고찰(考察)과 함의(含意)

박정하 ( Park Chung-ha ) 남도민속학회 2021 남도민속연구 Vol.43 No.-

청계동은 곡성군 곡성읍과 입면의 경계를 이루고 있는 동악산의 북쪽 끝단에 자리 잡은 골짜기의 명칭이다. 청계동이란 지명은 양대박의 문집인 _청계유고_에 처음 나타난다. 청계동은 1580년대에 남원양씨 가문의 양대박이 이 지역에 설촌한 마을의 명칭이기도 하다. 「청계동도」는 단면에 그려진 청계동 마을의 설촌 당시 마을의 설계도 또는 구성도이다. 청계동은 후손들이 길이 살아갈 터전으로 계획된 마을이자 양대박의 은거를 위한 별서이며 그의 이상을 펼치기 위해 설계한 정원이다. 혈족, 사승, 문생으로 얽힌 사대부 선비들과 호남사림의 교류를 위한 공간이다. 청계동은 순자강유역의 시단을 이끌었던 중추적 역할을 했던 지역이며 계곡이 아닌 순자강을 중심으로 거대한 원림을 형성했다. 이 원림에서 빼어난 주변의 경치를 즐기면서 남쪽과 북쪽지역 명현들 간의 인적교류를 통해 성리학의 실천을 도모하자는 도학적 실용성에 기반하고 있다. 이는 양대박의 스승인 우계 성혼의 학풍을 청계동에 실천하고 있다는 점이다. ‘우계(성혼)학파’의 도학사상에 따른 실학적 ‘무실학풍’을 충실히 계승하여 자신의 정체성으로 삼고 있은 것으로 나타난다. ‘우계학파’의 도학적 전통에 기반하여 계승한 실천적인 강조에 따라 ‘은거하면서 자신을 지키며 성인을 모표로 한다’는 측면, 특히 사회적 차원에서 청계동이라는 ‘원림’을 구성한 것으로 파악된다. 이 같은 실천적이고 실무적인 강조에 따라 ‘둔전법’을 활용해 운영, 청계동에서 의병 창의를 실천적으로 이룸으로서 도학의 완성을 이루고 있다. 본고를 통해 「청계동도」의 설계에 따른 보허정을 중심으로 정자를 복원할 것을 권고한다. 특히 보허정이 자리했던 지역인 사수골 입구의 화장실과 매표소를 철거하고 이 주변을 보정하여 청계원림을 복원할 것을 주문한다. 그러기 위해서는 기형적이고 편협적인 시각을 버려야 한다. 호남사단의 중핵지가 곡성지역까지 확대되어야 마땅할 뿐만 아니라 재정립되어야 한다. Cheonggye~dong is the name of a valley located at the northern end of Dongaksan Mountain, which borders Gokseong~eup and Gokseong~gun. The name Cheonggye~dong first appeared in “CheonggyeYugo”, a collection of the two major Parks. Cheonggye~dong is also the name of a village where the two families of Namwonyang lived in this area in the 1580s. “Cheonggye~ dongdo” refers to a blueprint or composition of the village during the Seolchon period of the Cheonggye~dong village drawn on a cross~section. Cheonggye~dong is a village planned for descendants to live on, a annex to the seclusion of two great gourds, and a garden designed to spread his ideals. It is a space for the exchange of Honam forests with the nobility of the nobility, which is intertwined with blood, monks and literati. Cheonggye~dong played a pivotal role in leading the foundation of the Sunja River basin, and formed a huge forest around the Sunja River, not a valley. It is based on the Taoist practicality of promoting the practice of Neo~ Confucianism through human exchanges between prominent figures in the southern and northern regions while enjoying the scenic beauty of the area. This means that the school spirit of the two Parks' teacher, Ugye Seonghon, is practiced in Cheonggye~dong. It appears that he has faithfully inherited the practical “unrealistic style” according to the Taoist ideology of the “Western (Sexual) School” and used it as his own identity. Based on the practical emphasis inherited based on the academic tradition of the “Ugye School,” it is believed to have formed the “Wonnim” called Cheonggye~dong in terms of “protecting oneself while living alone and modeling adults,” especially at the social level. In accordance with such practical and practical emphasis, the government has used the “Dunjeon Law” to complete the study by practicing the creation of righteous army in Cheonggye~dong. It is recommended that the pavilion be restored based on the Bohejeong Pavilion according to the design of Cheonggye~dongdo. In particular, the government ordered the removal of toilets and ticket booths at the entrance of Sasugol, where Bohejeong Pavilion was located, and the restoration of Cheonggye Garden Forest by correcting the surrounding area. In order to do so, we must abandon our deformed and narrow~minded views. The Honam Division's central core should not only be expanded to the Gokseong area, but also be re~established.

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.

말단 비대증의 임상적 특성

박은미,안용환,김현정,김병수,임종주,김하영,박병현,조정구 圓光大學校 醫科學硏究所 2004 圓光醫科學 Vol.19 No.2

Dimethyl-β-Cyclodextrin을 이용한 Omeprazole의 대체투여경로 개발

정미분,박승현,김하형,이광표 중앙대학교 약학연구소 1996 약학 논총 Vol.10 No.-

For the purpose of increaing the stability and bioavailability of omeprazole(OME), inclusion complexes of OME with demethyl-β-cycoldextrin(DMβCD) and hydroxypropyl-β-cyclodextrin(HPβCD) were prepared by freeze drying method. The interactions of OME with DMβCD and HPβCD in aqueous solutions and in solid states were investigated by solubility study. IR spectroscopy and DSC. The type of OME-DMβCD inclusion complex was found to be classified as Bs-type on phase solubility diagram, and the stoichiometric ratio of OME-DMβCD incousion complex was a 1:2 and stability constant was 359.46M^-1. The OME-HPβCD inclusion complex appeare to be AL type. The stoichiometric ratio was found to be 1:1, and stability constant was 34M^-1. Clear differences in a IR spectra and DSC curves were observed between the inclusion complex formation at pH 6.8. The mean dissolution time(MDT). which represents the degree of the rapidity of dissolution rate, was increased in the order of OME-DMβCD I.C(0.60) < OME-HPβCD I.C.(0.71) < OME-DMβCD P.M.(7.23) < OME-HPβCD P.M.(10.06). In order to compare simultaneously the intrinsic absorptivity of OME in the jejunum and nasal cavity of rats, the in situ nasal and jejunal perfusion method was employed as a new trial. The in situ recirculation study revealed that OME-CDs inclusion complexes rate proportionally increased the absorption of OME in nasal cavity(N) and the jejunum(J) of rats. The decreasing order of apparent OME permeability(Papp:cm/sec×10-5), corrected for surface area of absorption was as follows : 8.77±0.18(N, OME-DMβCD). > 5.97±0.17(N. OME-HPβCD) > 4.84±0.02(J. OME-DMβCD). 3.50±0.25(J. OME-HPβCD) at IPB pH 7.4. The present results suggest that OME-DMβCD inclusion complex may serve as a potential means for the nasal delivery of OME.

Max Frisch의 작품 "Dienstbuchlein"에 나타난 군과 사회 : die Armee und die Gesellschaft

朴忠河 관동대학교 1996 關大論文集 Vol.24 No.2

Das Ziel dieser Arbeit liegt in der Untersuchung der Gesselschaftskritik, die im Werk “Dienstbilchlein” Frischs erscheint. In diesem Werk will er mit Hilfe der Reflexion uber die erinnerte Vergangenheit einen Einblick in die gegenwartige Situation erhalten. In diesem Werk finden sich vortreffiche Bemerkungen uber die sozialen Unterschiede, die Unterschiede der Sprache, der Dienstkeidung und des verhaltens zwischen Offizieren und Mannschaften. In der Armee spiegelt sich die schweizerische Sozialstruktur selbst im Detail : Kastengeist. Der kastengeist, den Frisch in der Armee findet, ist fur ihn nichts anderes als der Ausdruck der gesellschaftlichen Struktur der Schweiz. Und der militarische Gehorsam erklart sich als Einubung in die zivile Unterordnung. Frisch demonstiert hier Klassenhierarchie. Frisch geht es hier auch um gesellschaftliche Auseinandersetzung, aber mit ganz eindeutien Akzenten : Object ist die Schweiz, ihr Selbstverstandnis, ihre Armee als Spiegel ihrer gesellschaftlichen Konstitution. Seine Erinnerungen gelten als Zerstorung eines Geschichtsbildes, das die Schweiz als antifaschistisch―demokratische Insel zeichnete. Frisch will am Beispiel des Militars jene Gefahren verdeutlichen, die mit der Entindividualisierung des Menschen durch das Kollektiv, mit dem Verlust der Einzelpersonlichkeit unter der alles nivellierenden Einwirkung herrschender Lebensauffassungen verbunden sind. Die Gesellschaft als moralische Institution schwebte Max Frisch vor. Er wunscht das Gewissen und die Gewissenhaftigkeit anstelle des blinden Arschlecker-Gehorsams. Immer in sich horchend, hat er die Gesellschaft erfahren. Dieses werk erinnert uns auch an die Asthetik der Provokation.

실내사무환경의 환경성담배연기(ETS)의 지표물질에 관한 연구

하권철,백남원,박동욱,윤충식,김원,최상준,박지영,최인자,김신범,강태선 한국산업위생학회 2003 한국산업보건학회지 Vol.13 No.2

The purpose of this research is to evaluate indoor office environment using the concentrations of nicotine, 3-enthenyl-pyridine(3-EP), and respirable suspended particulate(RSP), which are indicators for environmental tobacco smoke(ETS) and the correlations between indicators and environmental conditions(smoking density, smoking index). The mean air charge per hour (ACH) in smoking rooms was 10.4 and most of the smoking rooms showed non-compliance withe ASHRAE standard value except only one smoking rooms. The concentrations of RSP, 3-EP, nicotine showed log=normal distributions, and became different statistically depending on smoking condition(p〈0.01). The geometric mean concentration of RSP in smoking room was 441.7 ug/㎡ that is far exceeded environmental standard(150 ug/㎡). This implies that fine particulate in smoking room should be carefully controlled considering smoking density and ventilation fate. The mean concentrations of nicotine and 3-EP were 93.4 ug/㎥, respectively. The correlation coefficients between RSP and SI, 3-EP and SI, and Nicotine and SI were 0.67, 0.84 and 0.74, respectively. The correlation coefficient between nicotine and 3-EP, nicotine and RSP, and RSP and 3-EP were 0.76,0.78 and 0.57 respectively.

規模의 經濟에 의한 高等敎育機關의 敎育費 分析

최청일,박선하 동아대학교 인문과학대학 인문과학연구소 1995 인문과학연구 Vol.- No.2

The purpose of this study was to analyze the relationship between the educational expenditures and economies of scale in institutions of higher learning. Therefore, the following objectives were established. 1) To examine economics of scale in institutions of higher learning and the determinant of educational cost. 2) To estimate optimum educational cost through analysis of educational cost in institutions of higher learning. 3) To explore methods of improving tuition and fee system in institutions of higher learning. To accomplish the above objectives, this study focused on the examination of relevant literature. On the basis of this analysis, the following conclusions might be drawn. First, if the economies of scale in economics are applied to institutions of higher learning, the cost of production corresponds to educational cost and the output corresponds to students. In this sense, the economies of scale will be of great value in examining the optimum scale of institutions of higher learning. Second, educational cost is the main factor in determining the scale of institutions of higher learning. Therefore, the determinant of educational cost scale should involve personnel expenses, operation cost, and facility's expenditures. Through a detailed analysis of this, a plan should be considered with the objective of minimizing total educational cost. Third, the current tuition and fee system determines educational cost without regard for differences in fields of study or the total number of credits. These could be areas where improvement over the current tuition and fee system may be found.

비글개에서 신원방우황청심원의 급성 및 아급성독성시험

성하정,권오경,방명주,곽형일,이진영,신대희,박대규,정규혁,윤효인,조명행 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Single and 4 weeks oral administration of New wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs (3 males and 3 females) in acute experiments were administered orally with sinlge dose of 2,000 ㎎/㎏ and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NSCH, 160 ㎎/㎏/day (low dosage group), 400 ㎎/㎏/day (middle dosage group), 1,000 ㎎/㎏/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). LD_50 value for beagle dogs was more than 2,000 ㎎/㎏ per oral for both male and females. In animals administered with NSCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NSCH in beagle dogs is considered to be safe.