Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling

Kim, Donghee,Li, Hui Ying,Lee, Jong Han,Oh, Yoon Sin,Jun, Hee-Sook Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of α-SMA<SUP>+</SUP>/PCNA<SUP>+</SUP> cells was increased in the kidney cortex of <I>db/db</I> mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of p27<SUP>Kip1</SUP> was decreased. The expression of Krüppel-like factor 5 (KLF5) was upregulated in the kidney cortex of <I>db/db</I> mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of <I>db/db</I> mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.</P></▼1><▼2><P><B>Kidney disease: Mechanisms of diabetes-related damage</B></P><P>A potent molecular mediator of diabetic kidney disease induces its pathogenic effects via proteins that could be targeted with future drug therapies. Yoon Sin Oh
from Eulji University in Seongnam-si and Hee-Sook Jun from Gachon University in Incheon, both in South Korea, and colleagues treated certain cells found in the kidney’s glomerulus, the organ’s filtering unit, with a signaling molecule called lysophosphatidic acid (LPA) that is elevated in the blood of diabetic mice. They showed that LPA stimulated cellular proliferation and boosted the expression of proteins involved in regulating the cell cycle and a multipurpose signaling pathway. They then inhibited the activity of these proteins to prevent the kidney cells’ hyperproliferation, both in cell culture and in diabetic mice. The results highlight the potential of blocking mediators of LPA signaling to treat kidney-related complications of diabetes.</P></▼2>

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.

민간영리 스포츠 시설로서의 수영장의 라이프 사이클과 경영전략에 관한 연구

윤영복,박준희,정용준 조선대학교 사범대학 부설 교과교육연구소 1998 敎科敎育硏究 Vol.1 No.1

We made a research on the sports facility managers who manage the commerical swinning center in seoul, Kwang Ju, Pusan and Taegu, The results are as follows: (1) The competive strategy of swimming center consists of inner-differentiation strategy, out-differentiation strategy and low cost strategy. (2) Inner-differentiation strategy is emphasized by the swimming center which sets the goal for growth maintenance. (3) Competitive stratgy of swimming center is dertermined by each stage in the life cycle theory ① Introduction stage : The emphasis of strategy is laid on inner-differentiation strategy. ② Growth stage : The emphasis of strategy is laid on both inner-differentiation strategy and out-differentiation strategy ③ Decline stage : The emphasis of strategy is laid on out-differentiation strategy with the aim to maintain.

개에서 이중 결찰법을 통한 동맥관 개존증의 완치 예

윤헌영,정순욱,박희명,박철,정만복,김준영,한현정,황민,노병국,박상혁,장하영,박정윤 한국임상수의학회 2004 한국임상수의학회지 Vol.21 No.1

A ten months old, female Yorkshire terrier weighing 2.88 kg referred to veterinary teaching hospital of college of veterinary medicine, Konkuk University because of syncope, cough and dyspnea. First hematological and serum chemical test revealed thrombocytopenia, mild anemia, and increase of concentration of ALP (195 U/L). On 57 days later, second hematological and serum chemical test revealed polycythemia, increase of concentration of ALP (211 U/L), and Tchol (387 mg/dl). Right atrium enlargement, main pulmonary artery bulge and cardiomegaly (VHS = 11.5) were observed in radiographic findings. Ultrasonographic images showed both right and left ventricular dilation and turbulent flow between the descending aorta and the main pulmonary artery in color Doppler imaging. ECG showed left ventricular enlargement, SA block, and electrical alternant. Thoracotomy was performed through left fourth intercostal incision under isoflurane anesthesia. Patent ductus arteriosus was double ligated with 1-0 silk. Cough and dyspnea disappeared on 5 days after operation. Turbulent flow was not found in color doppler imaging of ultrasonography on 10 days after operation. Ten months later after the operation, syncope could not exist any more.

열대 지역에서 통일형 초다수성 벼 품종의 생육 및 수량성 비교

이지윤,준현,성환,손영보,송유천,한상익,박동수,권영업,이철원,이종희 忠北大學校 農業科學硏究所 2015 農業科學硏究 Vol.31 No.2

관상동맥 스텐트 내 재협착의 발생에 미치는 임상적 관동맥 조영술적 요인들

윤혁준,김기식,박형섭,이영수,현대우,한성욱,허승호,김윤년,김권배,박남희,원경숙 대한순환기학회 2003 Korean Circulation Journal Vol.33 No.12

페야쿠르트병을 이용한 오수정화시설의 유기물 처리 특성 및 서식 미생물 분류

전진화,김희숙,허시선,민병윤 경남대학교 환경문제연구소 1995 환경연구 Vol.17 No.-

The average concentration of BOD, SS, TKN and T-P of influent were 94.81, 105.58, 9.72㎎/L, respectively. Also, these average concentration of effluent were 7.94, 2.98, 18.21 and 4.95㎎/L, respectively. The corresponding removal efficiencies were 91.33% in BOD, 97.18% in SS, 67.30% in TKN and 49.0% in T-P. The process of this system was maintained stably because of flowing by gravity. The media used for this study was Yakult filter with specific surface area of 130㎡/㎥ and surface loading rate of 28㎡/㎥. In this system, the removal efficiencies of SS and sludge were higher than those of activated sludge process. Twenty eight senora and sixty eight species of aerobic bacteria were identified from floating water and Yakult filters in the septic tank. Especially, only two strains of the bacteria were found from the effluent. Alcaligenes, Corynebacterium, Flavobacterium, Pseudomonas, and Staphylococcus of the bacteria were found, and they were known as excellent bacteria for the degradation of organic matter. Also, Alcaligenes, Bacillus, Flavobacterium, Micrococcus, Proteus and Pseudomonas, which can denitrification organic matter, were found and phosphorus removal bacteria, Acinetobacter was identified.

냉장, 동결 및 해동후 재냉장이 소 등심육 지질중의 Cholesterol, Triglyceride 및 유리지방산의 함량에 미치는 영향

김명준,문윤희 慶星大學校 1998 論文集 Vol.19 No.1

Changes in lipid, fatty acid composition and MUFA/SFA(monounsaturated fatty acid/saturated fatty acid) ratios were studied in the Korean native and imported beef loin by aging and freezing. In non-frozen Korean native beef, frozen Korean native and imported beef, the cholesterol conentrations were not changed by the aging process, but increased with the freezing process(p〈 0.05). The triglyceride concentration was not changed in non-frozen Korean native beef, decreased significantly in unfrozen Korean native and imported beef by the aging process, and increased more or less with the freezing porcess. The total concentration of free fatty acids significantly (p<0.05) increased from all of these samoes, and the total concentration from frozen Korean native beef was higher than that non-frozen Korean native beef. The concentrations of cholesterol esters, fatty acids levels and the and the MUFA/SFA ratio from frozen and non- frozen Korean native and imported beef decreased significantly(p<0.05) with the aging and freezing process except for those of free fatty acid in the neutral lipid from non-frozen Korean native beef.

요근 농양이 동반된 Salmonella typhi 척추골수염 1예

조윤행,홍성수,김은옥,이미숙,김양수,우준희,배직현,류지소 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

저자들은 아직 국내에 보고된 적이 없는 S. typhi에 의한 척추골수염 환자에서 ciprofloxacin을 5주간 투여하여 임상적 호전을 보였던 증례를 경험하였기에 보고하는 바이다. Vertebral osteomyelitis by Salmonella infection is rare. Although it is known to be associated with sickle cell anemia, various hemoglobinopathies and immunosuppressive states, it may also occur in normal host. To date, vertebral osteomyelitis with Salmonella. typhi has not been reported in Korea. We experienced a case of spinal osteomyelitis due to S. typhi in a 48-year old man who was admitted because of low back pain for two months. MRI scan showed vertebral osteomyelitis in L1 & L2. Needle aspiration was performed by CT guidance. S. typhi was identified from aspirated pus. However, any organism was not identified from blood and urine cultures. He was treated with ciprofloxacin for 5 weeks successfully.

두경부 편평상피암에서의 MIB-1, p53, bcl-2와 apoptosis의 발현 및 상호 연관성

손용준,한지용,윤형기,장수원,윤혜경,김우형,이희철 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.4

Objective : Squamous cell carcinoma of the head and neck represents approximately 2.0∼4.0% of all malignant tumors, with an etiology closely associated with smoking, drinking and various genetic alterations. The purpose of this study was to investigate the correlation of MIB-1, p53, bcl-2 and apoptosis according to degree of differentitation of squamous cell carcinoma. Methods and Material : forty-eight cases of squamous cell carcinoma of the head and neck were selected for this study. MIB-1, p53, bc1-2 expression rate were studied by iromunogistochemical staining and the number of apoptosis observed by TUNEL method. Results : The expressioins of MIB-1, p53, bcl-2 and apoptosis were found in 56.3%, 50.0%, 14.6%, 85.4%, of 48 cases of squamous cell carcinoma, respectively. The expression of MIB-1, p53 and apoptosis were more higher in poorly differentiated cases than well differentiated cases. MIB-1 expression was related with p53 mutation (p<0.05) and apoptosis rate(p<0.05). Conclusion : From these results. the expressions of MIB-1, bcl-2 and apoptosis were related with degree of differentiation of squamous cell carcinoma and correlation among these parameters.