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>

당뇨병성 다발성 신경병증에 대한 Thioctic acid의 유효성 및 안정성에 관한 연구

박철영,김영설,오승준,우정택,김성운,양인명,김진우,최영길 대한당뇨병학회 2001 임상당뇨병 Vol.2 No.1

연구배경: 당뇨병성 신경병증은 당뇨병 환자에서 흔히 나타나는 합병증으로서 임상 증상은 가볍거나 없을 수도 있지만 많은 경우에 통증, 작열감, 이감각증이나 무감각증 등의 증상을 동반하지만, 이에 대한 명확한 기전이나 뚜렷한 치료방법이 없었다. 최근에 신경세포내 산화성 스트레스의 증가로 신경세포의 손상이 발생된다는 기전이 주목을 받으면서, 당뇨병성 신경병증 환자에게 항산화제인 thiotic acid를 사용하여 좋은 효과를 관찰한 논문들이 발표되었다. 이에 저자들은 한국의 당뇨병성 다발성 신경병증 환자에서 thiotic acid를 경구 투여 후에 신경병증에 의한 효과 및 안정성을 평가하였다. 방법: 모든 대상 환자에게 Thioctic acid 600㎎ 을 1일 1회 아침 식전 30분에 8주간 투여하여 당뇨병성 다발성 신경병증에 대한 TSS의 개선여부에 대한 임상적 유효성 및 이상반응, 내약성, 실험실적 지표의 변화를 통한 안정성을 관찰하였다. 결과: 치료시작 전에 관찰한 환자가 호소하는 증상은 통증이 가장 많았으며 무감각, 작열감, 이상감각 순의 빈도를 보였다. 통증, 작열감, 이감각증, 무감각증의 평균 TSS는 1차 방문시 5.8± 1.8, 2차방문시는 4.4±1.7, 3차 방문시는 3.1±1.1로 사용기판에 따라 통계학적으로 유의한 증상의 호전이 있었다. 또한 TSS의 개선 뿐만 아니라 통증, 작열감, 이감각증 및 무감각증 각각의 증상도 치료전과 치료 4주 후 및 치료 8주 후를 비교했을 때 통계학적으로 유의한 증상의 호전이 있었다. TSS가 1차 방문 시와 비교했을 때 3차 방문시에 30% 이상 개선되었을 때(1차 방문시에 TSS 4인 환자는 2점 이상 개선되었을때) 임상적으로 의미가 있는 반응으로 간주하고 계산한 반응률은 71.3%였다. 결론: 당뇨병성 다발성 신경병중 환자에 대해 항 산화제인 thioctic acid 600㎎ 경구 투여요법은 당뇨병성 신경병증의 증상완화에 유용하며, 안전한 것으로 사료된다. Background: The study was peformed to evaluate the efficacy and safety of oral treatment with the antioxidant α-lipoic acid (Thioctcid??) in diabetic patients with peripheral polyneuropathy. Methods: Thioctacid?? 600㎎ was orally administered once a day for 8 weeks in 61 diabetic patients with peripheral polyneuropathy. Neuropathic symptom(pain, burning, paresthesia, and numbness) were scored before, and of 4 and 8 weeks after treatment. In addition, neuropathy by the physician and patients at the end of treatment. The primary endpoint was the response role after 8 weeks treatment, defined as an improvement in the total symptom score of at least more than 30%. Results: Efficacy was evaluated among forty-four patients who had completely the study according to the protocol and safety was evaluated among all of 61 patients who had taken the study medication. The response rate after 8 weeks was 77.3%. The total symptom score was significantly decreased of 4-week, and further decreased of 8-week. All the individual scores for neuropathic symptom were also significantly reduced of 4-week and further decreased at 8-week. Conclusion: These finding indicate that oral treatment with thioctacid?? at a dose of 600㎎/day for 8 weeks will improve peripheral polyneuropathy in diabetic patients, without causing any serious adverse events.

혈당측정기 GlucoDr™ System의 평가

박철영,류미숙,우정택,김성운,김진우,김영설,안규정 대한당뇨병학회 2002 임상당뇨병 Vol.3 No.2

연구배경: 당뇨병 환자에서 엄격한 혈당조절은 환자의 예후와 밀접한 관련이 있다. 혈당조절을 철저히 하기 위해서는 자가 혈당 측정기의 사용이 필수적이라 할 수 있다. 또한 저혈당이 빈번하게 발생하거나, 위험요소가 있는 환자들에게도 유용하게 사용될 수 있다. 이에 저자들은 전기화학감지법의 원리를 이용하여 국내에서 처음 생산된 자가혈당측정기인 GlucoDr™ blood Glucose Testing System(ALL Medicus, Co, Korea)를 현재 국내에서 시판되고 있는 다른 제품과 비교, 평가하여 임상적 유용성을 살펴보고자 하였다 방법: 혈당측정기준장비는 YSI 2300 STAT Plus(YSI Incorporated, USA)를 사용하였으며 GlucoDr™외에 Glucocard(KDK, Japan), Precision QID(Abbott Laboratories, Co, USA), Glucotrend(Roche, USA), Surestep(Lifescan, USA)의 다른 혈당측정기를 같이 평가하였다. 정밀도, 직선성, 비교방법과의 상관관계 평가, 검체량에 따른 영향, 헤마토크리트에 따른 영향, 검사자에 따른 영향, 항응고제에 따른 영향들을 평가하였다. 결과: 본 연구에서의 주된 평가대상인 GlucoDr™의 평가결과, 정밀도를 나타내는 검사 내, 검사 간 변이계수는 8%이내였으며, 45~500mg/dL 범위에서 R²=0.9906, 0.9984 정도의 직선성을 나타내었다. 본 연구에 있어 비교방법으로 이용한 YSI 2300 STAT Plus와의 상관관계 및 정확도는 y = 1.0058x + 0.453, R = 0.9853인 것으로 나타났다. 검체량이나 검사자 및 항응고제에 따른 측정값에는 유의할만한 차이가 없는 것으로 나타났으나, 헤마토크리트가 증가 또는 감소함에 따라 최소 10%에서 최대 26% 가량의 영향을 받는 것으로 관찰되었다. 결론: GlucoDrTM는 국내 사용되는 다른 혈당측정기와 비교하여 유용할 것으로 생각된다. Background: Self-monitoing blood glucose devices are sidely used in monitoring and point-of-care testing for the management of diabetic patients. We performed the present study to evaluate the performance of the GlucoDr™ blood glucose testing system using an electrochemical technique. Method: The GlucoDr™ was evaluated for linearity, precision, comparison of method, the effect of sample volume, hematocrit concentration, reapplication, operator and application methods. Results: The GlucoDr™ showed good linearity for glucose concentrations ranging from 52mg/dl to 475mg/dl(r²=0.971). The single day, and day-to-day, CV were within 8%. Excellent correlation was found between the GlucoDr™ and YSI 2300 STAT Plus(y=1.0058x + 0.453, r²=0.9710). The sample volume, reapplication, operator and application method produced no significant effect on the test result. An overestimation in the glucose values was found with low hematocrit concentrations. There was no significant effect by the anticoagulants, with the exception of citrate. Conclusion: The GlucoDr™ showed good linearity, precision and correlation with the reference method and provided rapid and reliable result for blood glucose levels. Therefore, the GlucoDr™ seems appropriate for clinical use in the management of diabetic patients.

약국서비스 만족에 영향을 미치는 요인 분석 : 환자체감시간과 실 조제시간 비교를 중심으로

박성희,서준규,윤혜설,홍진영,박군제 한국의료QA학회 1998 한국의료질향상학회지 Vol.5 No.2

Purpose : To shorten processing time for variety of medical affairs of the patient at the outpatient clinic of a big hospital is very important to qualify medical care of the patient. Therefore, patient's waiting time for drug delivery after doctor's prescription is often utilized as a strong tool to evaluate patient satisfaction with a medical care provided. We performed this study to investigate factors influencing patient satisfaction related with waiting time for drug delivery. Methods : The data were collected from July 21 to August 12, 1998. A total 535 patients or their families who visited outpatient clinics of Inha University Hospital were subjected to evaluate the drug delivery time and the level of their satisfaction related, which were compared with those objectively evaluated by Quality Improvement Team. The reliability of the scale was tested with Cronbach's alpha, and the data were analyzed using frequency, t-test, ANOVA, correlation analysis and multiple regression. Results : The mean drug delivery time subjectively evaluated by the patient (16.1 13.0 min) was longer than that objectively evaluated (10.9 7.6 min) by 5.2 min. Drug delivery time objectively evaluated was influenced by the prescription contents, total amount or type of drug dispensed, etc, as expected. The time discrepancy between two evaluations was influenced by several causative factors. One of those proved to be a patient's late response to the information from the pharmacy which the drug is ready to deliver. Interestingly, this discrepancy was found to be more prominent especially when waiting place for drug delivery was not less crowded. Other factors, pharmaceutical counseling at the pharmacy, emotional status or behavior of a patient while he waits for the medicine, were also found to influence the time subjectively evaluated. Regarding the degree of patient satisfaction with the drug delivery, majority of patients accepted drug delivery time with less than 10 min. It was also found to be influenced by emotional status of the patient as well as kindness or activity of pharmaceutical counselor. Conclusion : The results show that, besides prescription contents, behavior pattern or emotional status of a patient, environment of the waiting place, and quality of pharmaceutical counseling at the pharmacy, may influence the patient's subjective evaluation of waiting time for drug delivery and his satisfaction related with the service in the big hospital. In order to improve patient satisfaction related with waiting time for drug delivery, it will be cost effective to qualify pharmaceutical counseling and information system at the drug delivery site or waiting place rather than to shorten the real processing time within the pharmacy.

의과대학생의 불안 및 자아강도가 스트레스 대처방식에 미치는 영향

박재석,류설영,장은진,김정범 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

교내 수도꼭지형 냉온수기의 생수 배출 부위와 생수에 존재하는 미생물의 분포

박창은,김설아,임미소,이다은,박유진 남서울대학교 2010 남서울대학교 논문집 Vol.16 No.1-1

The distributed species and number of viable microorganisms in drinking water were monitored according to water dispenser maintenance. our purpose was to investigate the distribution of bacteria in drinking water dispenser. To analyze possible dispenser contaminations sampling were performed from 14 locations in Namseoul University for 3 months from March to May, 2010. The isolated bacteria were identified by Gram stain and biochemical test using VITEKⅡ systems. The microorganism concentrations around the water discharge areas were measured and the average of total microorganisms was determined. The number of bacteria were measured by McFarland turbidity. The water and water discharge areas were separated and identified. The isolation rates of Gram positive cocci and Gram negative bacilli were 56.5%, 17.4% respectively. The frequently isolated bacteria were Staphylococcus epidermidis, Enterobacter aerogenes, Enterbacter sakazakii, Alcaligenes faecalis, Acinetobacter baumannii, Staphylococcus hominis, respectively. Further systematic studies are necessary with an emphasis on species identification. Key Words : Microorganisms, Water Discharge Areas, Drinking Water, McFarland

자료포락분석(DEA)를 이용한 보건의료의 효율성 측정

김남송,박홍섭,김은진,김설화,김정숙,김현아,김경숙,신지혜,최은정,양은진,유선미,유수진 圓光大學校 醫科學硏究所 2007 圓光醫科學 Vol.22 No.1

한국인 당뇨병 및 비당뇨병 환자에서의 뇌혈관 질환 유무에 따른 PAI-1 촉진자 유전자형과 인슐린저항성에 관한 연구

오승준,김영설,박철영,김덕윤,김성운,양인명,김진우,최영길,팽정령,정경천 대한비만학회 2000 The Korean journal of obesity Vol.9 No.2

연구배경 : 혈전현상을 특징으로 하는 질환에서는 Plasminogen activator inhibitor-1 (PAI-1) 이 높은 활성도를 보이는데, PAI-1 치는 당뇨병, 심근경색증, 비만 등에서 높다고 밝혀진 바 있다. 또한 당뇨병 환자들의 합병증의 주요한 병인은 죽상경화증으로 혈전현상이 특징인 질환에서 증가하는 PAI-1이 당뇨병 환자에서 높다. 목적 : 정상인에서의 PAI-1 유전자 촉진자의 유전자형의 분포 및 혈액농도를 관찰하고, 당뇨병 및 뇌혈관 질환 환자군에서의 PAI-1 유전자 촉진자 유전자형의 분포 및 혈액농도를 측정하여 정상인과 차이점을 알아본다. 당뇨병 환자군에서의 혈장 PAI-1 치와 인슐린 저항성, 전구 인슐린 등과의 상관관계를 살펴보고, 인슐린저항성과 대혈관질환의 지표로 사용될 수 있는지 알아보았다. 방법 : 대상으로는 정상인 76명, 제2형 당뇨병 환자 56명, 뇌혈관질환이 동반된 제2형 당뇨병 환자 48명, 뇌혈관질환 환자 51명을 선택하여, 환자의 혈액에서 인슐린, 공복시 혈당, 전구인슐린, 중성지방, 총콜레스테롤 및 기타 생화학 검사 및 이학적 검사를 시행하였다. 환자의 DNA를 채취하여 전사개시 -675bp를 포함하는 대립형질 특이 시발체를 사용하여 중합효소 연쇄 반응을 실시하여, 그 유전자형을 판독하였다. 결과 : 정상 대조군 76명 (46.4±11.1세), 2형 당뇨병 환자 56명 (58.3±12.6세), 뇌경색증 환자 51명 (63.1±13.2세) 대상으로 하였다. PAI-1 촉진자 유전자형의 (4G/4G, 4G/5G, 5G/5G)빈도는 정상 대조군이 각각 23.7%, 75.0%, 1.3%, 뇌경색 환자군이 19.6%, 66.7%, 13.7%, 뇌경색이 동반된 당뇨병 환자군이 33.3%, 58.3%, 8.3% 였다. (X2=12.6, p=0.05). 이러한 사실은 서구인에 비해 4G/4G, 5G/5G 동형 유전자형이 낮은 결과였다. 각 군별 혈장 PAI-1 농도는 정상 대조군 13.4, 1.8 ~ 65.2 ng/mL (중앙값 , 범위 ) 2형 당뇨병 환자군 14.4, 2.9 ~ 47.8 ng/mL, 뇌경색 환자군 21.9, 6.2 ~ 154.7 ng/mL , 뇌경색이 동반된 2형 당뇨병 환자군 28.8, 3.2 ~ 139.3 ng/mL 로 차이를 보였다 (p=0.000). 전체 대상에서 PAI-1 촉진자 부위의 유전자형에 따른 PAI-1 활성도와 항원 농도는 차이를 보이지 않았다. 그러나 PAI-1 활성도는 혈중 중성지방, 전구인슐린, 체질량지수와 독립적인 상관관계를 보였다 (p=0.000, p=0.000 and p=0.005). 결론 : 결론적으로 PAI-1 촉진자 부위의 유전자형은 뇌경색증의 지표는 아니며, PAI-1 활성도를 결정짓는 인자는 유전적 요인보다는 혈중 중성지방, 전구 인슐린, 체질량지수와 같은 대사적 요인으로 생각된다. Plasminogen activator inhibitor-1 (PAI-1) is known be related to insulin resistance and several components of the large vascular disease. Notably, the high frequencies of diseases such as coronary heart disease or stroke are related to type 2 diabetes complications. We studied to find out whether the PAI-1 promother genotype could be a marker for cerebral infarction in type 2 patients. Subject patients were; 56 type 2 diabetics (age 58.3±12.6), 51 patients with cerebral infarction (age 63.1±13.2), 48 type 2 diabetics with cerebral infarction (age 64.8±9.3) , and 76 healthy control (age 46.4±11.1). The 4G/5G genotype of PAI-1 promoter was evaluated by polymerase chain reaction and endonuclease digestion. PAI-1 promoter genotype frequency (4G/4G, 4G/5G, 5G/5G) was 23.7%, 75.0% and 1.3% in healthy control, 17.9%, 67.9% and 14.3% in type 2 diabetes patients, 19.6%, 66.7% and 13.7% in cerebral infarction patients, 33.3%, 58.3% and 8.3% in type 2 diabetics with cerebral infarction (X^2=12.6, p=0.05). This finding is lower in frequency of 5G/5G homozygote than that reported in Caucasians. The plasma PAI-1 concentrations according to the disease were 13.4, 1.8 ~ 65.2 ng/mL (median, range) for healthy control, 14.4, 2.9 ~ 47.8 ng/mL for type 2 diabetes, 21.9 6.2 ~ 154.7 ng/mL for cerebral infarction , and 28.8, 3.2 ~ 139.3 ng/mL, for cerebral infarction with type 2 diabetes (p=0.000). In the all subjects, PAI-1 concentration and activity of PAI-1 promoter genotype did not show any significant difference. However, the PAI-1 activity was independently associated with serum triglyceride level, plasma proinsulin and BMI (p=0.000, p=0.000 and p=0.005 respectively). We concluded that PAI-1 genotype is not a marker for the cerebral infarction ; however, the genotype is related to PAI-1 concentration , and therefore it seems to be that metabolic factors such as triglyceride level or plasma proinsulin or BMI are more in relations with determining the PAI-1 concentration than the genotype.

심한 골병변으로 발현된 기능성 낭종성 부갑상선 선종

전숙,김영희,박지영,고관표,박철영,김덕윤,우정택,김성운,김진우,김영설,고석환 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.2

낭종성 부갑상선 선종과 심한 골병변을 동반한 부갑상선 기능항진증은 매우 드문 질환으로서, 저자들은 양측 고관절의 통증을 초기 주소로 내원한 환자에서 고칼슘혈증과 부갑상선 호르몬 증가, 골병변의 방사선적 소견을 통해 부갑상선 기능항진증을 진단하고, 경부 초음파와 컴퓨터 단층 촬영, 부갑상선 스캔검사 및 수술중 부갑상선 낭종액 검사 등을 통해 기능성 부갑상선 낭종의 한 종류인 낭종성 부갑상선 선종을 진단하고 수술적 제거를 통하여 정상화된 1예를 경험하였다. A cystic parathyroid adenoma is rare. A case of primary hyperparathyroidism, with the cystic formation of a parathyroid adenoma and a severe bony lesion, is reported. A 52-year-old male was admitted due to pain in both hips and for evaluation of hypercalcemia. The plasma level of the intact parathyroid hormone (iPTH) was elevated to 1424 pg/mL. Ultrasonography and the computed tomography revealed a parathyroid cyst on the left thyroid lower pole. Parathyroid scintigraphy detected a parathyroid adenoma. A radiograph showed a subperiosteal bone resorption on the phalanges, and a brown tumor (osteitis fibrosa cystica) on the femur shaft was noted. A surgical excision of the parathyroid adenoma was performed. The PTH level in the cystic fluid was increased. A histological examination confirmed a cystic parathyroid adenoma. The PTH level was normalized after the operation (J Kor SOC Endocrinol 18:214-220, 2003).

정상과 갑상선 종양조직에서 사람 IGF-I 유전자의 발현

김성운,장현하,박상미,김덕윤,우정택,양인명,김진우,김영설,김광원,고석환,홍성화,최영길 경희대학교 유전공학연구소 1993 遺傳工學論文集 Vol.5 No.-

Many of the growth-promoting properties of growth hormone(GH) are mediated by insulin-like growth factor-I(IGF-I), a highly conserved circulating 70-amino acid peptide. Recent studies have shown that multiple mechanisms influence IGF-I gene expression, including transcription from two promoters, alternative RNA splicing, and variable polyadenylation. In thyroid tissue, thyroid stimulating hormone(TSH) and IGF-I are the most possible candidates for follicular cell proliferation and hypertrophy. Actually IGF-I had autocrine and paracrine effect for tissue growing. We prepared thyroid tumor tissue mRNAs using single step method for detecting IGF-I levels according to different tissues, i.e., thyroid adenoma or papillary thyroid carcinoma. We used Northern blot analysis for IGF-I mRNA and RNase protection assay (RPA) for IGF-I transcription start sites. For Northern blot, we used whole human IGF-I cDNA as a DNA probe and for RPA, we used IGF-I exon 1 containing noncoding promoter 1 as a riboprobe. We got good RNA bands from Northern blot analysis around 1 kb (IGF-IA) and 7.5 kb (IGF-IB) region. To clarify the amount of both IGF-IA and IB mRNAs, we measured autoradiographied signal of IGF-I mRNAs bands using densitometer. In IGF-IA signals, there's no change among liver and thyroid tissues, but in case of IGF-IB mRNA bands, the signal was markedly increased in thyroid carcinoma tissues than that of normal thyroid tissue (85% vs 14%). In the study of RPA, all thyroid tissues used the same transcription start sites as those of liver's. We concluded that that this different regulation of IGF-I mRNA was originated from tissue specificity. That meant some tissue specific transcription factor/s were related to tissue IGF-I expression.