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>

연령증가에 따른 혈압요소들의 좌심실비대 및 관동맥질환과의 관련성

박재석,박창규,박미영,박재형,김용현,나진오,신성희,서순용,홍순준,박성미,임홍의,김응주,서홍석,오동주,노영무 대한순환기학회 2004 Korean Circulation Journal Vol.34 No.2

捻轉法이 竝行된 鍼刺戟 및 電鍼刺戟이 鎭痛效果에 미치는 影響

Park, Dong-Seok,Kim, Ji-Hoon,Min, Byung-Il,Oh, Soo-Myung 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Dong-Seok Park¹, Ji-Hoon Kim¹ and Byung-Il Min, Soo-Myung Oh,³¹Department of Acupuncture and Moxibustion, College of Medicine, ²Department of Physiology, College of Medicine, And ³East-West Medical Research Institute, Kyung Hee University,Seoul, Korea. Analgesic Effect of Manual Acupuncture and Electroacupuncture combined with Twirling Method. Proceeding of International Symposium on East-West Medicine Seoul. 187-200, 1999.-Twirling the needle (TN) is one of several needing methods frequently used for acupuncture in the oriental medicine. The present study was conducted to see if TN enhanced the antinociceptive effect produced by plain-or electroacupuncture in the rat tail flick test. Rats (Sprague-Dawley, 200-300g)lightly anesthetized with thiopental sodium(40mg/kg, i.p.) were used in the tail-flick test. The basal reaction time for tail-flick was 2 sec. For "plain" acupuncture(PA), a needle was inserted for 20 min into a Chock-samni (ST36) acupuncture point which (is located at the anterior tibial muscle and about 10mm below the knee joint). For electroacupuncture(EA), train-pulses(3 Hz,0.3-ms pulse width, 0.2-0.3mA) were applied to the inserted needle for the period of insertion. For combining TN with either PA or EA, TN was performed during the each acupuncture period. Two methods for TN were used; twirling 3 times for 1 second persisted for 1 min in every 5 mins(long-duration and long-interval;LDLI) and twirling 3 times for 1 second persisted for 10 sec in every 1 min(short-duration and short-interval;SDSI). PA and EA produced an increase in tail flick latency (TFL); peak increases were 21.3±5.1% and 42.1±17.3% of the pre-acupunture control, respectively, and occurred immediately after cessation of 20min-acupuncture. Performing TN combined with PA increased TFL more than PA itself by showing a greater peak increase in TFL when performed with a SDSI-TN than with a LDLI-TN(60.6±12.5% and 42.7±22.7% of the pre-acupuncture control, respectively). Performing TN combined with EA also increased TFL more than EA itself and a greater peak increase in TFL was observed with a SDSI-TN as compared to a LDLI-TN(77.5±13.8% and 67.3±14.0% of the pre-acupuncture control, respectively). These results indicate that TN enhances both PA-and EA-produced antinociception where an greater enhanced antinociception than a LDLI-TN. It is suggested that performing a SDSI-TN combined with EA seems to be one of the most effective ways to produce analgesia.

요통 환자의 기립위 및 좌,우 외측굴곡시 방사선 사진을 통한 요추 회전변위 분석

허동석 ( Dong Seok Heo ),박석우 ( Seok Woo-park ),박영회 ( Young Hoi Park ),금동호 ( Dong Ho Keum ) 한방재활의학과학회 2003 한방재활의학과학회지 Vol.13 No.2

Objectives : Rotation on vertebra body is common reason causing low back pain and leg radiating pain patients. The present study investigated analysis of the radiological findings on lumbar vertebra rotation between erect position and erect both lateral bending position lumbar AP views in low back pain patients. Method : The study population consisted of 70 patients(outpatients and inpatients clinic of the Dept. of Oriental Rehabilitation Medicine, Dong-Guk Oriental Medical Hospital in Bundang) who were evaluated with X-ray findings of erect position and erect both lateral bending position lumbar AP views. First, patients were measured erect position lumbar AP views by Nash-Moe`s degree. Second, patients were measured erect both lateral bending position lumbar AP views by intervertebral disc space at convexity region and rotation on lumbar vertebral body. They divided into four groups by type of Grice and Cassidy`s classification. Results : 1. The distribution of sex in the low back pain with leg radiating pain was male 30(42.86%) cases, female 40(57.14%) cases. According to age, 30-40s 23(32.9%) cases, 40-50s 15(21.4%) cases, 20-30s 13(18.6%) cases, 50-60s 9(12.9%) cases, 60-70s 5(7.1%) cases, 70-80s 3(4.3%) cases, each 10-20s and 80-90s one case (1.4%). 2. According to Nash-Moe`s degree by erect position lumbar AP view, the grade 0 was male 8(11.4%) cases, female 10(14.3%) cases, the grade Ⅰ was male 17(24.3%) cases, female 22(31.4%) cases, the grade Ⅱ was male 5(7.1%) cases, female 8(11.4%) cases. 3. According to symptoms, first, patients with low back pain were male 22(31.4%) cases, female 20(28.6%) cases. second, patients with leg radiating pain were male 8(11.4%) cases, female 20(28.6%) cases. 4. According to type of Grice and Cassidy`s classification by erect both lateral bending position lumbar AP views, the type Ⅰ was normal group 7(10.0%) cases, the type Ⅲ and Ⅳ were abnormal group each 15(21.4%) cases, 48(68.6%) cases. 5. According to abnormal group in Nash-Moe`s degree by erect position lumbar AP view, the grade Ⅰ was 39(55.7%) cases and then abnormal type Ⅲ, Ⅳ of Grice and Cassidy`s classification were 5(7.1%) cases, 33(47.1%) cases, the grade Ⅱ was 13(18.6%) cases and then abnormal type Ⅲ, Ⅳ of Grice and Cassidy`s classification were 1(1.4%) case, 12(7.1%) cases. So the relationship between rotation of vertebra by erect position lumbar AP view and type of Grice and Cassidy`s classification by erect both lateral bending position lumbar AP views had significant correction(p<0.05). 3 6. According to analysis of symptoms and X-ray findings by erect both lateral bending position at convexity region, patients with leg radiating pain were 28 cases. In the total of 28 cases, 25 cases had shown rotation of vertebra and intervertebra disc space narrowed at convexity region, while 3 cases didn`t have shown. 7. According to abnormal rotation of vertebral body on erect position, the number of group L4 was 48(32.7%) cases the most, group L3 was 43(29.3%) cases, the next group L2 was 30(20.4%) cases. Group L4, L3, L2 had significantly connection with fixation group on erect both lateral bending position(p<0.05). Conclusions : We concluded that the abnormal rotation of lumbar vertebral body had connection with the low back pain and leg radiating pain patients. So we must regard functional X-ray such as erect both lateral bending position lumbar AP views to early find cause.

봉독(蜂毒)의 연구 경향에 대한 분석 -국내 학위논문 중 봉독에 관한 연구를 중심으로-

박장우 ( Jang Woo Park ),허동석 ( Dong Seok Heo ),윤일지 ( Il Ji Yoon ),오민석 ( Min Seok Oh ) 한방재활의학과학회 2006 한방재활의학과학회지 Vol.16 No.2

Objectives : To research the trend of the study related to bee venom and to establish the hereafter direction for the study on bee venom therapy. Methods : I referred to national assembly library and national library of Korea, with `bee venom`, `apitoxin`, `apitherapy`, `bee sting`. After collecting all the theses about bee venom published by domestic university from 1992 to 2005, I figured out number and percentage of theses according to university, year, major field of study, subject. In case of subject, I classified and analyzed it with anti-inflammation effect;travail effect;immunity relation;safe treatment & prevention of side effect of bee venom. Results : The following results were obtained in this study. 1. In the arrangement by the year, the theses started to publish after 1992, and the number of theses has been increasing rapidly since 2000. And it has been decreasing since gaining the summit at 2003. 2. Classified by university, Kyung-Hee University published the most theses, and other theses were published by Kyung-Won University, Dong-Guk University, Kyoung-San University, Seoul National University order. 3. Classified by the major field of study, number of theses was the most by 69 in oriental medicine, next, it was 8, 2 in veterinary science and medicine. 4. Analyzed by the subject, numbers of theses that is related to anti-inflammation effect are 39(50%), numbers of theses related to travail effect are 15(18%), numbers of theses related to immunity are 19(23%), numbers of theses related to safty are 7(8%). 5. Theses that is related to anti-inflammation effect ; travail effect of bee venom shaded to mechanism study inclination after 2002 in primitive effect proof study inclination. Theses that is related to immunity of bee venom shaded to anticancer-related research inclination after 2000 in primitive immunity promotion effect study inclination. 6. In the study for safe treatment & prevention of side effect of bee venom, there were reports bee venom secures when it is injected in wide region, by low concentration, in 3 days cycle. 7. Theses related to bee venom are for the most part experiment theses by 76. Conclusions : As see in above result, safety of bee venom was proved, I think that the more clinical access by using bee venom should be achieved because objective, scientific basis was readied for effect of anti-inflammation, travail, immunity promotion, anticancer etc.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

Brief introduction of Butterfly(Lepidoptera) from Myanmar

Ja Lang LIM,Jinyoung PARK,Ik Je CHOI,Yong Kyun OH,Eui Seok JEONG,Dong Pyeo LYU,U Pho Cho,Khin Mar Myint,Khin Mar Yi,Jong Kyun PARK 한국응용곤충학회 2013 한국응용곤충학회 학술대회논문집 Vol.2013 No.04

Myanmar is located in the south-east Asia peninsular and it is flanked by five neighboring states: Bangladesh, India, China, Laos and Thailand. It is located 10~22 degree north latitude, to 92~101 degrees east longitude. Myanmar has a tropical climate with three seasons in Myanmar. Hot season (March through April), rainy season (May through October) and the cool season (November through February). The coastal regions can get very hot and humid, especially before the rainy season. Myanmar has a monsoon season from May to October when there are heavy rains and often flooding. The investigation was carried out during the dry season(2013) in Nat Ma Taung National Park and Popa Mountain Park. Popa Mountain Park is located in Kyawpadaung Township, Myinchan district, Mandaly Division. The area is 49.63 square miles. Its coordinates are 29°31'60" N and 27°43'60" E. Nat Ma Taung National Park, Myanmar treasure is in Mindut District of Chin State and its area of 279 square miles. It is the third highest mountain in Myanmar with the height of 10,500 feet. Its coordinates are 21°14'00" N and 93°54'00" E. As the result, butterflies(Lepidoptera) collected in the two regions were about 60 species of 7 familys. Collecting dates, expedition activities, photo of main specimen and information of Myanmar were provided.

골수 검사상 양성 혈구 탐식 조직구가 나타난 소아의 임상적 고찰

박진아,박주영,박지민,박샛별,김흥식,전동석,Park, Jin A,Park, Joo Young,Park, Ji Min,Park, Seat Byoul,Kim, Heung Sik,Jeon, Dong Seok 대한소아청소년과학회 2002 Clinical and Experimental Pediatrics (CEP) Vol.45 No.8

목 적: 혈구 탐식 조직구 증식증은 양성 질환으로는 드물게 치명율이 높은 질환으로, 발열, 간비장 종대, 림프절 종대 등의 증상이 있고, 검사 소견에서 양성의 혈구 탐식 조직구가 나타난 경우 진단되나 치료가 혼란스러운 경우가 많다. 골수 검사상 양성의 혈구 탐식조직구가 나타난 예들의 임상적 특징을 분석하여 진단 및 치료 방향과 예후 판정에 도움이 되고자 이 연구를 시행하였다. 방 법 : 1995년 1월부터 2001년 11월까지 계명대학교 동산병원에서 골수 검사상 양성의 혈구 탐식 조직구가 나타난 환아 30례를 대상으로, 특징적 임상 증상, 진찰 소견, 혈액 검사 소견, 골수 검사 소견, 치료 방법과 예후에 대하여 임상 기록지를 후향적으로 분석하였다. 또한 골수 도말에서 혈구 탐식 조직구의 수에 따라 a few, some, many로 나누어 환아의 예후와 비교하였다. 결 과 : 골수 검사상 양성 혈구 탐식 조직구를 보인 예들을 분석한 결과 이들의 연령 분포는 2개월에서 15세로, 평균 연령은 5.6세였고, 남녀비는 2.3 : 1로 남아가 많았다. 입원 당시 증상으로는 발열이 가장 많았으며, 호흡기 증상, 위장관 증상 등의 순이었고, 평균 발열 기간은 19.5일이었으며, 진찰 소견은 간비종대, 피부 발진, 림프절 비대 순으로 많았다. 혈액 검사 소견상 백혈구 감소증이 23례(76.7%)로 가장 많았고, 혈소판 감소증이 16례(53.3%), 빈혈이 15례(50.0%), 간기능 검사 이상이 15례(50.0%)로 나타났다. 기저 질환으로 급성 림프구성 백혈병, 악성 림프종 등 면역 저하된 상태가 5례였고, 건강했던 경우가 25례 였으며, 관련 질환의 종류로는 패혈증, 폐렴, 전염성 단핵구증 등의 순이었고, 원인으로는 세균이 많았으며, 바이러스로는 EBV가 4례였고, candida가 1례였다. 골수 도말 소견상 세포 충실도가 정상이 25례(83.3%)였고, 5례(16.7%)에서 감소되어 있었으며, 혈구 탐식 조직구의 수에 따라 분류하였을 때, some이 15례(50.0%), many가 9례(30.0%), a few가 6례(20.0%)이었다. 치료는 보존 요법, 항생제와 항바이러스제, 항진균제, 면역 글로불린, steroid, etoposide, cyclosporine 등의 병용 요법을 시행하였다. 사망율은 30명 중 8명으로 26.7%였으며, 연령이 낮은 군과 혈구 탐식 조직구 수가 some 이상인 경우에 사망률이 높았다. 결 론 : 고열, 간비종대, 범혈구 감소증과 간기능 이상 등의 소견을 보이는 환아에서 조기에 골수 검사를 시행하여 혈구 탐식 조직구가 보일 때, 원인 치료 및 대증 요법과 함께 면역 화학 요법을 시행하는 것이 예후에 도움이 될 것으로 생각되며, 골수 소견과 예후와의 관계는 지속적인 연구 관찰이 필요할 것으로 사료된다. Purpose : The aim of this study is to find a method to diagnose and treat children who showed benign hemophagocytic histiocytes in bone marrow examination. Methods : We analyzed the clinical data of thirty patients retrospectively who showed benign hemophagocytic histiocytes in bone marrow examination from January 1995 to November 2001 at Keimyung University Dong-san Hospital. Bone marrow histiocytes were classified into a few, some, and many according to the number of histiocytes comparing with the white cells. Results : The age of thirty patients ranged from two months to 15 years. The median age was 5.6 years with male predominance(2.3 : 1). The most frequent clinical manifestation was fever; others were respiratory symptom, hepatosplenomegaly, lymphadenopathy and skin rash(in order of frequency). Common laboratory findings were leukopenia, thrombocytopenia, anemia and abnormal liver function test. Infection was present in 30 patients; causative organisms were documented in 15 patients, and bacterial infection was more common. Epstein Barr virus was the cause of infection in four patients. Bone marrow examination showed a few(20.0%), some(75.0%) and many(30.0%) hemophagocytic histiocytes. Combination immunochemotherapy including immunoglobulin, steroids and cyclosporine were helpful in 22 out of 30 patients. The mortality rate was high in young patients who showed some to many hemophagocytic histiocytes. Conclusion : Bone marrow examinations and early detection of histiocytes will be helpful in children who have fever, hepatosplenomegaly and abnormal liver function test. Immunochemotherapy were helpful and further investigation will be needed for the detection of the relationship between the bone marrow findings and prognosis.

Aspergillus sp. ISR 균주를 통한 콜레스테롤 합성저해제 lovastain의 생산

박상은,조미현,신동화,황승환,박천석 경희대학교식량자원개발연구소 2005 硏究論文集 Vol.24 No.-

본 연구에서 한국 토양에서 분리된 lovastatin 생산 균주인 Aspergillus sp. ISR 균주를 이용하여 여러 배지 조성 성분이 lovastatin의 생산에 미치는 영향을 관찰하였다. 탄소원으로는 lactose보다 glycerol 5%가 가장 효과적이었으며 질소원과 인산염의 경우는 기본 RPM배지 조성과 농도에서 보다 효과적인 것을 발견하지 못하였다. 복합영양원으로 rapeseed meal 보다는 대두박이 보다 효과적이어서 저렴한 배지원으로 사용이 가능할 것으로 사료된다. 최종적으로 최적화된 배지를 사용하여 52 mg·L^(-1)의 lovastatin을 생산할 수 있었고 이는 기존의 RPM 배지보다 수율이 4.5배 증가한 것이다. 좀 더 효과적인 lovastatin의 생산을 위하여 회분식 발효에 대한 연구와 분자유전학적인 연구를 통한 고생산 균주의 제조에 대한 연구가 진행중이다. Effects of various nutritional components on the production of lovastatin were investigated in the Aspergillus sp. ISR. Among various carbon (C) sources, glycerol was determined to be the most effective C source at the concentration of 5% (v/v). In case of nitrogen sources, 0.2% (w/v) KNO_(3) efficiently induced the lovastatin production in Aspergillus sp. ISR. Interestingly, the addition of soybean meal into the production medium enhanced the lovastatin production compared to the rapeseed meal. Conclusively, Aspergillus sp. ISR produced 52 mg·L^(-1) of lovastatin in the optimized medium containing 5% (v/v) glycerol, 0.2% (w/v) KNO_(3), 0.3% (w/v) KH_(2)PO_(4), and 0.3% (w/v) soybean meal, which was 4.5 times higher than the amount produced using the standard RPM (rapeseedmeal production medium).