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>

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.

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.

간세포암과 감별이 어려웠던 악성중피종 치험 1예

김선문,허원석,채경훈,강윤세,정재훈,김연수,박기오,문희석,이엄석,김석현,성재규,이병석,이헌영,신경숙,조준식,송인상,강대영 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Malignant peritoneal mesothelioma is a rare neoplasm that arises from the mesothelium of a serosal cavity and is a rapidly fatal disease with a median survival of 4 to 12 months for untreated cases. Recently, we experienced a case with malignant peritoneal mesothelioma who was suspected hepatocelluar carcioma by abdominal CT scan and was confirmed by biopsy including immunohistochemical stain(calretinin) after surgery. We performed tumor excisions and wedge resection of the liver(segment Ⅷ)and inserted Tencoff catheter in abdominal cavity at 25th day of post-operation. We treated with intraperitoneal paclitaxel(25mg/m^(2)/day for 5 days) six courses monthly. She was well tolerable and is still living without any evidence of recurrence for 14th month of post-operation.

Cholelithiasis complicated with biliary sludge and urolithiasis in a dog

Seung-gon Lee,Dong-gun Kim,Joon-seok Lee,Ho-hyun Kwak,Hyun-sook Nam,Heung-myong Woo*, In-Chul Park**, Changbaig Hyun1,In-chul Park,Chang-baig Hyun 한국임상수의학회 2006 한국임상수의학회지 Vol.23 No.3

A 10-year-old intact female Miniature Schnauzer dog was referred with the primary complaint of persistentanorexia, remittent fever, vomiting and abdominal pain. Hemogram suggested a chronic inflammatory disease. Serumbiochemistry showed moderate hepatobiliary cellular damage with severe cholestasis. Abdominal radiography andultrasonography revealed hepatomegaly, choleliths and sludges in gall bladder and small stones in urinary bladder. Basedcholecystectomy and cystectomy, choleliths and uroliths were removed from gall bladder and urinary bladder,respectively. The clinical condition was dramatically improved after surgery.

한의진단명과 진단요건의 표준화 연구 II (표준화 실례) : 2차년도 연구결과 중간 보고

양기상,최선미,최승훈,안규석,박경모,박종현,김성우,신승호,정우열,전병훈,고현,김정범,신상우,김성훈,김동희,권영규,엄현섭,장혜옥 한국한의학연구원 1996 한국한의학연구원논문집 Vol.2 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the second year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows; - differential diagnosis according to condition of body fluid, differentiation of syndromes according to the state of qi and blood, differential diagnosis according to relative excessiveness or deficiency of yin and yang(氣血陰陽津液辨證) - differentiation of diseases according to pathological changes of the viscera and their interrelation - analyzing and differentiating of febrile diseases in accordance with the theory of the six channels(傷寒辨證) The individual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name(異名), notion of diagnosis pattern, index of differentiation of symptoms and signs(辨證指標), the main point of diagnosis, analysis of diagnosis pattern(證候分析), discrimination of diagnosis pattern(證候鑑別), a way of curing a diseases(治法), prescription(處方), herb in common use(常用藥物), diseases appearing the diagnosis pattern(常見疾病), documents(文獻調査). This study was carried out on the basis of the Chinese documents and references.

Gilbert 증후군에서 열량 제한 시험과 Phenobarbital 자극 시험의 의의(14예)

이헌영,채경훈,정재훈,강윤세,김연수,문희석,박기오,이엄석,김선문,김석현,성재규,이병석,이강욱 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Gilbert 증후군은 인구의 7%에서까지 나타날 수 있는 매우 흔한 증후군으로서 비진행성인 양성의 만성적 경과를 치하며, 간질환의 증상과 징후가 없는 경한 비포합형 고빌리루빈혈증이 특징인 일종의 체질적인 증상으로서 혈장 빌리루빈 농도에 대한 사춘기의 영향 때문에 10대와 20대에 자주 진단이 된다. 따라서 임상적인 중요성은 미약하지만 높은 빈도가 예상되는 점에 그 중요성이 부여되어야 할 것이다. 따라서 적정한 임상적 진단법으로 기왕에 소개된 열량제한 시험과 phenobarbital 유도 시험을 시행하고 이들의 진단적 가치를 알아보기 위하여 본 연구를 시행하였다. 1990년 7월부터 1999년 4월까지 충남대학교병원에 내원하여 HBsAg, IgG anti-HBc 및 anti-HCV가 음성이고, 간 초음파 스캔에서 이상이 없으며, 혈청 AST, ALT 및 AP가 정상인 비음주자에서 경한 비포합형 고빌리루빈혈증이 있는 14예의 환자들을 대상으로 ^(99m)Tc-DISID 스캔을 시행하였으며, 기저 치 총빌리루빈 및 포합형 빌리루빈 치를 측정한 다음에 하루에 400Kcal로 48시간동안 제한한 열량 제한 시험을 시행하였고, phenobarbital을 하루 60mg씩 5일간 투여한 후에도 각각 총빌리루빈과 포합형 빌리루빈 치를 검사하여 비포합형을 구하였다. 대상 환자들은 모두 14예로서 남자가 11예(78.6%)였고 여자가 3예(21.4%)여서 3.7:1로 남자에서 많았으며, 20대가 6예(42.9%), 30대가 역시 6예(42.9%) 및 40대가 2예(14.2%)로서 2,30대가 대부분(85.8%)이었다. 열량 제한 시험 후의 총빌리루빈 치, 비포합형 및 포합형 빌리루빈 치들은 평균 각각 5.5±2.7, 4.2±2.3 및 1.3±10mg/dL 로서, 시험 전 치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg/dL 보다 유의하게(p=0.001, p=0.001, p=0.023) 상승하였다. 포합형 빌리루빈 치도 유의하게 상승하였으나 비포합형의 상승보다는 훨씬 낮아서 주로 비포합형이 증가하였다. phenobarbital 투여 중 설사가 발생하여 중단한 1예를 제외한 13예에서 열량 제한 시험 후에 상승하였던 총, 비포합형 및 포합형 빌리루빈 치가 phenobarbital 유도 시험후에는 2.0±1.1, 1.5±0.8 및 0.5±0.4mg/dL로서 열량 제한 시험 결과보다 유의하게 낮아졌고(p=0.00, p=0.000, p=0.001), 열량 제한 시험 전의 기초치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg.dL 보다도 더욱 낮아졌으며 유의한 차이(p=0.001, p=0.02, p=0.005)를 나타내었다. 14예에서 시행한 ^(99m)-Tc DISIDA 스캔에서 9예(64.3%)가 정상이었고, 5예(35.7%)에서는 심장 및 신장으로의 간외 섭취가 3예였고, 60분까지 소장 배출이 없는 배설 지연 예와 담낭 수축 불량 예가 각각 1예 씩 발견되었다. Phenobarbital 투여시험에서 민감도가 열량제한시험에 비해 더 높았다(92.3%와 50.0%). Gilbert 증후군에서 1일 400 Kcal로 48시간의 열량제한 시험과 1일 60mg의 phenobarbital을 5일간 투여하는 유도 시험은 편리하고 유용한 임상적인 진단법으로 이용할 수 있다고 생각된다. 그러나 열량 제한 시험에서는 증가 기준의 통일이 필요하다고 유추되며 phenobarbital 유도 시험이 민감도가 더 높은 것으로 생각된다. Gilbert's syndrome is very frequent and benign chronic process characterized by mild, intermittent, unconjugated hyperbilirubinemia without any symptom and sign of liver disease. Previously intoduced caloric restriction test and phenobarbital stimulation test as two appropriate clinical tests had been examined and their diagnostic values were reevaluated. Fourteen patients with mild, persistent, unconjugated hyperbilirubinemia were included. Subsequently caloric restriction has been applicated by 400 Kcal/day for 48 hours and phenobarbital has been prescribed by 60 mg/day for 5 days. Therafter serum levels of total and direct bilirubin were measured. Most of the patients were third and fourth decade(85.8%) and male predominant. Each basal serum levels of total, indirect and direct bilirubin were 3.0±0.8, 2.2±0.8 and 0.7±0.4 mg/dL. After caloric restriction test, each levels were increased significantly to 5.5±2.7, 4.2±2.3 and 1.3±1.0 mg/dL(p=0.001, p=0.001, p=0.023). After phenobarbital stimulation test for 13 patients had been practiced, increased levels of each bilirubin after caloric restriction test were decreased significantly to 2.0±1.0, 1.5±0.8 and 0.5±0.4 mg/dL(p=0.000, p=0.000, p=0.001) and these levels were significantly lower than basal levels(p=0.001, p=0.02, p=0.005). The sensitivities of caloric restriction test were 85.7%, 50.0%, and 71.4%, 35.7%(1.0, 1.5 mg increase of total bilirubin and 1.0, 1.5 mg/dL increase of indirect bilirubin). The sensitivities of phenobarbital stimulation test were 93.2% and 92.3% at criteria of 1.5 mg/dL increase of total bilirubin and indirect bilirubin. On the diagnosis of Gilbert syndrome, caloric restriction test and phenobarbital stimulation test are convenient and useful diagnostic tools in clinical face. And also phenobarbital stimulation test has higher sensitivity than caloric restriction test. Furthermore, standardization of bilirubin increment would be necessary in caloric restriction test.

고체 기준물질을 이용한 indium-doped CaZrO₃수소센서의 수소 감지 특성

박동섭,홍현석,박진수,박종욱 경북대학교 센서기술연구소 2002 센서技術學術大會論文集 Vol.13 No.1

관계문법에 의한 수동문 연구

박현석 대불대학교 1999 論文集 Vol.5 No.1

The passive construction of natural language has been an interesting and inviting subject to linguists. It is quite natural, therefore, that many linguists should have been interested in trying to unveil the phenomenon of passive construction. The purpose of this paper is to analyse the English and Korean constructions mainly under the framework of Relational Grammar(이하 RG). For this, I will first examine the English passive constructions under the Relational Grammar based on the grammatical relations and different syntactic levels, which are posited as linguistic primitives. Then I will deal with two types of Korean passives and formulate syntactic constraints on passivization in Korean, paying special attention to what nominals can undergo passivization.

兒童權利協約의 履行

朴賢錫 國際人權法學會 1998 國際人權法 Vol.2 No.-