DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic modification of endothelial nitric oxide synthase

Won, Kyung Jong,Jung, Seung Hyo,Jung, Soo Hyun,Lee, Kang Pa,Lee, Hwan Myung,Lee, Dong-Youb,Park, Eun-Seok,Kim, Junghwan,Kim, Bokyung Oxford University Press 2014 Cardiovascular research Vol.101 No.3

<P><B>Aims</B></P><P>DJ-1/park7, a multifunctional protein, may play essential roles in the vascular system. However, the function of DJ-1/park7 in vascular contractility has remained unclear. The present study was designed to investigate whether the DJ-1/park7 is involved in the regulation of vascular contractility and systolic blood pressure (SBP).</P><P><B>Methods and results</B></P><P>Norepinephrine (NE) elevated contraction in endothelium-intact vessels in a dose-dependent manner, to a greater extent in DJ-1/park7 knockout (DJ-1/park7<SUP>−/−</SUP>) mice than in wild-type (DJ-1/park7<SUP>+/+</SUP>) mice. Acetylcholine inhibited NE-evoked contraction in endothelium-intact vessels, and this was markedly impaired in DJ-1/park7<SUP>−/−</SUP> mice compared with DJ-1/park7<SUP>+/+</SUP>. Nitric oxide (NO) production (82.1 ± 2.8% of control) and endothelial NO synthase (eNOS) expression (61.7 ± 8.9%) were lower, but H<SUB>2</SUB>O<SUB>2</SUB> production (126.4 ± 8.6%) was higher, in endothelial cells from DJ-1/park7<SUP>−/−</SUP> mice than in those from DJ-1/park7<SUP>+/+</SUP> controls; these effects were reversed by DJ-1/park7-overexpressing endothelial cells from DJ-1/park7<SUP>−/−</SUP> mice. Histone deacetylase (HDAC)-1 recruitment and H3 histone acetylation at the eNOS promoter were elevated and diminished, respectively, in DJ-1/park7<SUP>−/−</SUP> mice compared with DJ-1/park7<SUP>+/+</SUP> controls. Moreover, SBP was significantly elevated in DJ-1/park7<SUP>−/−</SUP> mice compared with DJ-1/park7<SUP>+/+</SUP> controls, but this elevation was inhibited in mice treated with valproic acid, an inhibitor of Class I HDACs including HDAC-1.</P><P><B>Conclusion</B></P><P>These results demonstrate that DJ-1/park7 protein may be implicated in the regulation of vascular contractility and blood pressure, probably by the impairment of NO production through H<SUB>2</SUB>O<SUB>2</SUB>-mediated epigenetic inhibition of eNOS expression.</P>

푸른길 공원의 대기 환경 특성에 관한 연구

민경우,이경석,박옥현,윤관주,김도술,박세일,정원삼,이대행,조영관,Min, Kyoung-Woo,Lee, Kyoung-Soek,Park, Ok-Hyun,Yoon, Kwan-Ju,Kim, Do-Sool,Park, Se-Il,Jeung, Won-Sam,Lee, Dae-Hang,Cho, Young-Gwan 한국환경보건학회 2015 한국환경보건학회지 Vol.41 No.3

Objectives: This study aimed to survey the characteristics of air quality and meteorological conditions in a greenway park. Methods: We measured meteorological and health related factors, including noise, particulate matter ($PM_{10}$) and selected gaseous air pollutants at three locations in a greenway park and on a general roadside as comparison. The measurements were repeated four times from April to October 2014. Results: The average air temperature in the greenway park was $20.7^{\circ}C$ which was $1-2^{\circ}C$ lower than on the general roadside. The average $PM_{10}$ concentration in the greenway park was $85.0{\mu}g/m^3$, a level 2-3 times lower than that at the roadside. The noise level at the greenway site was 4.4 dB(A)- 23.0 dB(A) lower than at the roadside. The average CO, $CO_2$, $SO_2$ and NOx concentrations in the greenway park were lower than at the roadside. The average phytoncide and anions concentrations in the greenway park were higher than at the roadside. Conclusions: The urban forest of the greenway park may have some impact on air quality and meteorological conditions.

미세혈관 협심증 환자의 임상상 및 지표에 관한 연구

박상호,온영근,김현정,이태훈,길효욱,김현건,박수진,송해정,한대희,방덕원,신원용,이내희,김성구,권영주 순천향의학연구소 2003 Journal of Soonchunhyang Medical Science Vol.9 No.1

Background : Microvascular angina or syndrom X is heterogenous and encompasses different pathogenetic entities. Several studies suggest that microvascular angina have good prognosis and occurs predominantly in postmenopausal women. Lipoprotein (a), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, homocystein, CRP and fibrinogen are the independent risk factor of acute coronary syndrome and are the chief underlying cause of atherosclerosis. We investigated clinical characteristics and markers in patients with microvascular angina. Methods : We studies 23 patients diagnosed with microvascular angina and 16 control group with negative treadmill exercise test and no significant coronary angiogram. We investigated clinical characteristics in patients group and evaluated symptom during a follow-up period of 4.2± 2.5 month. Exercise time in treadmill exercise test was compared between patients and control group. We assessed the level of markers, such as lipoprotein (a), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, homocystein, CRP and ESR in two groups. Results : There is no difference in age between two groups. Patients group had a tendency to increase in female, hypertension, DM, and smoking history, but there was no statistical significance difference. Exercise duration time was significantly decreased in patients with microvascular angina (p<0,05). Serum lipoprotein (a), total cholesterol, LDL-cholesterol, HDL-cholestrol, Triglyceride, ESR, Fibrinogen and Homocystein value were no significant difference between microvascular angina and control group. Only CRP was significantly high in patients with microvascular angina (p<0.05). Conclusion : There was no statistical significance difference in age, sex, hypertension, DM and smoking history between two groups but patients group had a tendency to increase the prevalence in hypertension, DM and smoking history, female. Also, Symptom improvement and disappearance in follow-up was presented in 11 patients of 19(57.9%). Exercise tolerance was worse in patients group than control group. CRP value was significantly higher in patients group than control group. There was no statistical significance difference in lipoprotein (a), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, homocystein, ESR and Fibrinogen between two groups.

급성 심근허혈에 의해 윤발된 승모판 폐쇄부전의 기전에 관한 실험적 연구

강덕현,송현,송재관,김현숙,이재환,임희영,이재원,박성욱,박승정,송명근 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.8

알레르기 환자에서 한방 이외의 대체 요법의 사용 현황에 대한 다기관 조사

이현정 ( Hyun Jung Lee ),이재현 ( Jae Hyun Lee ),이용원 ( Yong Won Lee ),김철우 ( Cheol Woo Kim ),동헌종 ( Hun Jong Dhong ),박해심 ( Hae Sim Park ),조영주 ( Young Joo Cho ),조진희 ( Jin Hee Cho ),조상헌 ( Sang Heon Cho ),편복양 ( 대한내과학회 2011 대한내과학회지 Vol.80 No.1

Background/Aims: The use of unproven complementary/alternative medicine (CAM) to treat allergies is popular in Korea. We conducted a multicenter survey of the current use of CAM other than herbal medication in Korean allergy patients. Methods: This study enrolled 510 adults with allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, and chronic urticaria, from ten hospitals. They underwent a structured questionnaire interview and clinical assessment of the prevalence, motivation, costs, and subjective assessment of CAM. Results: Of the patients, 16.7% used at least one type of CAM to treat their allergic diseases. Common types of CAM were diet (48.6%), aroma therapy (23.8%), massage (14.3%), breathing exercises (7.6%), baths (5.7%), and mind control (5.7%). The therapeutic effects of CAM included improved in patients using mind control (50%), diet (50%), breathing exercises (75%), and baths (33.3%), but worse in patients using aroma therapy (28%), and massage (26.7%). About 36.4% of the patients used CAM more than four times per year, and the average cost per CAM user was 370,000 won/year. The main reason for trying CAM was `hope to improve my constitution`. Conclusions: CAM is used widely for treating allergic diseases in Korea. Detailed knowledge of CAM and patient education are important. Further studies of the clinical efficacy of CAM are needed. (Korean J Med 2011;80:68-77)

이면성 및 도플러 심초음파도를 이용하여 진단한 선천성 거대 좌회선지-좌심실 관동맥루

진승원,박준철,이영중,유병현,박현옥,김용주,윤호중,김재형,홍순조,최규보,권종범,원용순,박건 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.4

흉선종 제거후에 발생한 재생 불량성 빈혈 : 증례보고

전원선,이상철,김현정,배상병,김찬규,이남수,박노진,이규택,박성규,홍대식,박희숙,원종호 순천향의학연구소 2007 Journal of Soonchunhyang Medical Science Vol.13 No.2

Thymoma is associated with myasthenia gravis, Pure red cell aplasia, and autoimmune diseases such as autoimmune hemolytic anemia, aplastic anemia, and hypogammaglobulinemia. It's association with aplastic anemia is rare and aplastic anemia appearing after surgical removal of thymoma is especially rare. The authors hereby report a case of aplastic anemia occuring in a patient who was diagnosed with thymoma and myasthenia gravis and had the tumor surgically removed. The patient was treated with anti-thymocyte globulin, cyclosporin, and prednisolone, and showed partial remission with hematologic improvements after 12 months.

비혈연간 동종골수이식에 의해 치료된 중증 재생불량성빈혈 1예

김현중,이홍기,이방훈,이창근,이종태,정현식,김원석,윤성수,강원기,박근칠,김대식,고영혜,박찬형 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

비혈연간 동종골수이식은 혈연간 동종골수이식이 불가능한 환자에서 기존의 면역역제요법으로 효과가 없었던 경우나 재발한 경우에 적응증이 될수 있다. 이식 거부와 이식편대숙주병의 발생이 골수 이식의 성공률을 감소시키므로, 보다 강력한 conditioning regimen의 사용과 T cell이 제거된 골수를 사용하는 것이 필요하다. 기존의 high dose corticosteroid나 cyclosporine에 대하여 불응성인 이식편대숙주병의 치료를 위해서 ATG와 Mycophenolate mofetil (Cellcept®) 의 사용이나 Tacrolimus, Methotrexate와 같은 다른 면역억제제치료를 고려해 볼 수 있다. It is known that allogenic bone marrow transplantation is the most effective treatment for aplastic anemia. However, this treatment is only applicable to a minority of patients because the proportion of patients who have HLA-matched siblings about 25% to 30% of all the aplastic anemia patients. In the case of the absence of HLA-matched donor, unrelated allogenic bone marrow transplantation is considered. However, (because of severe acute and chronic GVHD and graft failure) the success rate of this approach is only 20~30%. Recently, it was reported that increased immunosuppressive condition combined with T cell depletion of the marrow graft would result in greater success. There was no case of successfully treated aplastic anemia patient by unrelated allogenic bone marrow transplantation in Korea. Here, we report a case of severe aplastic anemia successfully treated with unrelated allogenic bone marrow transplantation.

관해유도 항암요법을 받는 백혈병 환자에서 진균 감염증의 예방 : 무작위 배정법과 이중 눈가림법에 의한 Fluconazole과 Nystain의 효과에 관한 다기관 공동연구 A Randomized, Double-blind, Multicenter Trial to Compare Fluconazole with Nystatin

최강원,오명돈,배현주,백경란,박선양,김병국,신완식,강문원,진종률,박종원,김춘추,김동집,한지숙,민유홍,이선주,고윤웅 대한화학요법학회 1993 대한화학요법학회지 Vol.11 No.2

Fluconazole의 진균 감염증 예방 효과와 안전성에 관하여 3개 대학병원에서 관해유도화학요법을 받는 급성 백혈병환자를 대상으로 무작위 배정법과 너도나도 누가림법에 의하여 연구하였다. 모두 62명의 환자에게 fluconazole(100㎎ bid) 또는 nystatin(1,000,000IU/day)을 무작위로 투여하였다. 투약은 관해유도화학요법과 같은 날짜에 시작하여 호중구수가 1,000㎣이상으로 회복되거나 진균 감염증이 확인되거나 의심되어 Amphotericin-B를 시작하거나, 약과 관련된 부작용이 나타날 때까지 계속하였다. 진균 colonization은 fluconazole군에서 감소하였으나 nystqatin군에서는 증가하였다, 표재성 진균감염증으로 nystatin군에서 C. albicans 진균혈증 1례와 C.parasilosis 진균혈중 1례가 발생하였다. 경험적 항진균요법으로 Amphotericin-B를 투여한 경우는 fluconazolerns 34명중 7례(21%), nystatinrns 28명중 10례(36%)였다(p<0.05). Fluconazole군과 nystatin군 사이에 부작용이나 사망률에 차이는 없었다. 결론적으로, fluconazole은 관해유도화학요법을 받는 급성 백혈병환자에서 진균의 colonization을 줄이는데 효과적이고 안전한 항진균제이다. We made a randomized, double-blind, multicenter trial to compare the efficacy and safety of fluconazole with nystatin for prevention of fungal infections in patients with acute leukemia. Sixty-two adult undergoing remission induction chemotherapy for cute leukemia were enrolled. Patients were randomly assigned to receive either fluconazole (100㎎ bid) or nystatin(1,000,000IU×6/day) with corresponding placebo. The study drug was started in initiation of chemotherapy and continued until recovery of neutrophil counts(>1,000/㎣), development of proven or suspected invasive fungal infection, or the occurrence of drug-related toxicity. Fungal colonization decreased in fluconazole(F) group, however increased in nystain(n) group. Superficial fungal infection occurred in 1 of 34 F group, whereas invasive fungal infection developed in 3 of 28 N group. Empirical amphotericin-B therapy was given in 7 of 34(21%) F group and 10 of 28(36%) N group(p>0.05). The incidence of drug-related side effects and overall moratlity were similar in both study groups.

국소성 분절성 사구체 경화증의 완전 관해 후 발병한 IgA 신병증 1예

임현민,김현정,박민석,주혜원,최원,김상현,박원도 인제대학교 2006 仁濟醫學 Vol.27 No.-

We report a rare case of primary glomerular disease with IgA nephropathy in a 43-year old man. 7-years ago, he was diagnosed with minimal change nephrotic syndrome. After treatment with steroid for 1-year, azotemia and proteinuria were improved. But, nephrotic range proteinuria was relapsed within 1 week after cessation of steroid. Renal biopsy revealed focal segmental glomerulosclerosis, and achived a complete remission with the use of steroids and cyclophosphamide. Then, he was followed up with normal renal function for 4-years. On admission, the patient showed generalized edema and marked proteinuria. In 3rd renal biopsy, mesangial proliferative glomerulonephritis with diffuse global sclerosis was observed. Electron microscopy showed electron-dense deposit on the mesangium with slight mesangial proliferation, and immunofluoroscence microscopy showed granular deposits of IgA and IgM. These features were consistent with IgA nephropathy, different from results of previous biopsies. The pathogenesis of IgA nephropathy occurred with primary FSGS is not clear, as well as treatment. Now, proteinuria is improving, steroid and cyclophosphamide are probably useful for the disease.