Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

견운모의 고품위화 정제에 관한 연구

김진호,김경남,박현,김남수 三陟大學校 産業科學技術硏究院 2005 産業科學技術硏究論文集 Vol.10 No.-

In this study which it sees for the development of beneficiation technique of the sericite raw materials at the clay for the removal of a iron and separation of quartz hydrocyclone with the high intensity magnetic separator it introduced in beneficiation process. The characteristic analysis of the raw materials and the beneficiation sericite were investigated by the X-ray Fluorescence Spectrometer(XRF), X-ray Diffractometer(XRD), Scanning Electron Microscope(SEM), Thermal Gravimetic-Differential Thermal Analyzer(TG-DTA) and Paticle Size Analyzer(PSA). The iron content(0.91wt%) and mean particle size(3.55μm) were decreased by the hydrocyclone, high intensity magnetic separator and spray dryer, respectively.

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.

관상동맥 스텐트 삽입술을 시행한 환자에서 안지오텐신 전환효소 억제제와 안지오텐신 수용체 차단제가 재협착에 미치는 영향

김연경,정진원,윤경호,박은미,송미진,최준호,이은미,유남진,김남호,오석규 圓光大學校 醫科學硏究所 2006 圓光醫科學 Vol.21 No.1

외과적 노출술을 이용한 매복된 하악 제 1 대구치의 자발적 맹출 유도

김은정,김난진,조호진,김현정,김영진,남순현 大韓小兒齒科學會 2004 大韓小兒齒科學會誌 Vol.31 No.4

하악 제 1대구치 매복의 발생 빈도는 전체 인구의 0.01%로 드물게 나타난다. 매복의 원인으로는 맹출 공간의 부족, 과잉치, 치성 종양이나 낭과 같은 맹출로상의 장애물, 유전적 요인, 내분비 질환, 외상 등이 있다. 하악 제 1대구치의 매복으로 인해 하안면 고경의 감소, 낭의 형성, 치관 주위염, 인접치의 치근 흡수, 부정 교합 등의 부작용이 생길 수 있으며, 치료 방법으로는 외과적 노출술, 교정적 견인, 외과적 재위치술, 발거 등이 있다. 다음의 두 증례는 하악 제 1대구치의 미맹출을 주소로 내원한 환아에게 외과적 노출술을 시행하여 원심 경사 매복된 하악 제 1대구치의 자발적 맹출을 유도한 증례들이다. Impaction of mandibular first molar is relatively rare and its overall frequency has been reported to be 0.01%. The etiology of impaction are lack of eruption space, physical obstacles such as supernumerary teeth, odontomas or odontogenic tumors, hereditary factors, functional disturbances of endocrine glands and traumas. Impaction of mandibular first molar can result in a short lower facial height, formation of a follicular cyst, pericoronal inflammation, resorption of the roots of neighboring teeth and malocclusion. The treatment options available for impacted teeth include surgical exposure, orthodontic forced eruption, surgical repositioning and surgical removal of unerupted molar. This report presents two cases of distally tilted and impacted mandibular first molars which were treated by surgical exposure. In these cases, we could observe spontaneous eruption of the impacted mandibular first molars after surgical exposure.

원격 영상 정보 시스템의 개발

김선호,유선국,김용구,박성욱,김성림,김남현 대한의료정보학회 1996 Healthcare Informatics Research Vol.2 No.1

혈액암환자에서 조혈모세포 이식 후 따르는 헤르페스 바이러스 감영 양상

이호섭,탁희상,신성훈,김양수,남성진,김혜수,박진희,정수현,김성빈,김예나 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.1

배경 : 헤르페스바이러스과에는 단순포진 바이러스(HERPES SIMPLEX VIRUS, HSV), 수두대상포진 바이러스 (VARICELLA-ZOSTER VIRUS, VZV), 엡스타인-바 바이러스 (EPSTEIN-BARR VIRUS, EBV), 그리고 거대세포 바이러스 (CYTOMEGALOVIRUS, CMV) 등이 있다. 헤르페스바이러스 감염은 혈액암환자에서 조혈모세포 이식 환자에서 전파 (dissemination), 이차감염, 세균 중복 감염의 심각한 합병증을 일으킬 수 있다. 하지만 항암약물치료를 받는 림파종 환자에서 항 바이러스 약제의 사용 용량과 기간에 대한 concensus는 없다. 헤르페스바이러스 감염에 대한 발생율과 위험인자를 후향성으로 분석하였다. 방법 : 고신대학교 복음 병원에서 1995년 6월부터 2009 년 2월 사이에 새롭게 진단되어 조혈모세포 이식을 받은 전체 58명의 환자들이 후향적으로 현 연구에 등록했다. 헤르페스 바이러스 감염은 임상적 진단, 혈청학적 검사 또는 병리학적 진단에 기초하여 확진한다. 환자들의 특성은 다음과 같다: 평균 연령은 44세 (범위 19-62세)였고 남녀비는 30:28이었다. 등록된 질환은 백혈병 (n=9, 15.5%), 림프종 (n=30, 51.7%), 다발성 골수종 (n=12, 20.7%), 재생불량성 빈혈 (n=6, 10.3%) 그리고 골수이형성증후군 (n=1, 1.7%)이 포함되었다. 결과는 chi-squre test나 independent samples T test를 사용하여 분석되었다. Multivariate analysises에 대해 logistic regression test를 사용하였다. 결과 : 15명의 환자들 (25.9%)에서 조혈모세포 이식후 헤르페스 바이러스 감염이 발생하였다. 조혈모세포 이식 5년간 누적 발생율은 53.9%였다. Univariate analyses에서 헤르페스 바이러스 감염에 대한 유의한 위험 인자는 없었다. 하지만 조혈모세포 이식후 생존 기간(40.18 ± 30.14 months vs 20.06 ± 26.67 months, p=0.018)은 헤르페스 바이러스 감염의 낮은 발병율과 유의한 관련성이 있었다. 이식 편대 숙주질환 (GVHD)의 존재 (37.5% in developed GVHD vs 0% in no GVHD, p=0.200), 동종조혈 모세포 이식에서 면역억제요법의 기간 (15.98 ± 14.02 months vs 6.78 ± 3.67 months, p = 0.374)은 헤르페스 바이러스 감염에 대한 위험인자가 아니었다. 결론 : 조혈모세포 이식 후 생존 기간은 어사이클로비어 예방을 받은 혈액암 환자에서 헤르페스 바이러스 감염의 낮은 발병율과 연관성이 있는 것으로 보인다. 저용량의 어사이클로비어 예방은 헤르페스 바이러스 감염의 고위험군인 조혈모세포 이식을 받은 혈액암 환자에 필요하리라 생각된다. Background : Herpesviridae family includes herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus, etc. Herpesviridae viral infection (HVI) can lead to serious complications including dissemination, secondary infection, bacterial superinfection in patients with hematologic malignancy following hematopoietic stem cell transplantation (HSCT). But there was no consensus on the dose and duration of antiviral agents prophylaxis in patients undergoing chemotherapy. We retrospectively analyzed the incidence and the risk factors for HVI. Method : A total of 58 patients who newly diagnosed and received HSCT with prophylaxis of acyclovir at the Kosin University Gospel Hospital, Busan, Korea between June 1995 and February 2009 were enrolled retrospectively in the current study. HVI was confirmed based on clinical diagnosis, serologic test or pathologic diagnosis. The characteristics of the patients were as follows: the median age was 44 years (range 19-62 years) with a female-to-male ratio of 30:28. The enrolled diseases included leukemia (n=9, 15.5%), lymphoma (n=30, 51.7%), multiple myeloma (n=12, 20.7%), aplastic anemia (n=6, 10.3%) and myelodysplastic syndrome (n=1, 1.7%). The results were analyzed using a chi-square test and independent samples T test. For the multivariate analysis, we used logistic regression test. Results : Fifteen patients (25.9%) developed HVI after HSCT. The cumulative incidence of HVI was 53.8% at 5 years after HSCT. In univariate analysis, there was no significant risk factor for HVI. The presence of graft-versus-host disease (GVHD) (37.5% in developed GVHD vs. 0% in no GVHD, p=0.200), duration of immunosuppressive therapy (IST) in allo-SCT (15.98 ± 14.02 months vs. 6.78 ± 3.67 months, p = 0.374) were not risk factors for HVI. Conclusion : The incidence of HVI was similar to that in historical other studies. There was no risk factor associated with development of HVI. Most of the HVI occurred within the first 24 months after transplantation. So long term use of antiviral prophylaxis may be needed to prevention of HVI after HSCT.

악관절 융기 증강술을 통한 습관성 악관절 탈구환자의 치험례

김일규,신주호,오성섭,최진호,김형돈,오남식,김의성 대한악안면성형재건외과학회 2000 Maxillofacial Plastic Reconstructive Surgery Vol.22 No.2

Recurrent mandibular dislocation is frequent morbidity of temporomandibular joint relatively. There are many etiologic causes in TMJ disorders but, difficult to find obvious one. Various treatment methods have been utilized for a mandibular dislocation. It is categorized into two groups broadly - nonsurgical or surgical methods. The basic rationale of the surgical method is to allow free movement of the condyle by reducing height of articular eminence or to limit anterior excessive movement of the condyle by increasing height of articular eminence or soft tissue anchoring procedure. In this case, 69 year-old woman was treated by augmentation of the articular eminence with mandibular symphysial bone graft leading to osteosynthesis without difficulty. As a result, favorable postoperative outcome was obtained functionally without any complication or recurrence.

석청(Mad-honey) 복용 후 유발된 부정맥 1예

김용철,김남호,김승환,최준호,박은미,이상재,이은미,유남진,윤경호,오석규,정진원 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

석청에 포함된 grayanotoxin에 의해 독성 작용이 나올 수 있으며, 이러한 독성 작용은 일반적으로 24시간 이내 저절로 회복된다. 최근에 본 저자들은 석청 복용 후 발생한 심실빈맥을 경험하였기에 보고하는 바이다. 49세 남자가 호흡곤란으로 내원하였으며, 내원당시 분당 40회 정도의 동성 서맥이 관찰되었고, 수액을 투여하던 중 심실 빈맥이 발생하였다. 항부정맥제를 투여 후 정상 동율동으로 전환되었으며, 특별한 이상 없이 4일 후 퇴원하였다. Mad-honey intoxication caused by the consumption of honey producted from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The toxic effects of mad-honey poisoning are rarely fatal and generally last for no more than 24 hours. We experienced one case, a 49 years-old man who presented with dyspnea after ingestion of mad-honey. He showed marked sinus bradycardia with < 40 beats per minute on admission. The cardiac rhythm was changed to ventricular tachycardia immediately. These features resolved completely in 24 hours with continuous infusion of amiodarone(600 mg per day) and fluids. We report the case of intoxication of mad-honey as a presentation of fatal cardiac arrhythmia.

林土의 有機物의 分解速度와 無機養料의 垂直分布에 關한 考察

金遵敏,張楠基,鄭玩鎬 서울대학교 교육대학원 학술연구회 1966 論文集 - 서울대학교 교육대학원 Vol.3 No.-

Kim Choon Min, Chang Nam Kee and Chung Whan Ho: Decomposition rate of plant residue and the vertical distibution of mineral nutrients in the woodland soil. The relationship between decomposition rate of litter and the amount of mineral nutrients dispersed to the soil horizons were studied on the oak and pine forest stand. The results are as follows: 1. Decomposition rate of litter was highest in the F horizon of the oak stand, however in the pine stand it was highest in H horizon. 2. The correlation coefficients between decomposition rate and humus, organic carbon, moisture content, calcium, phosphorus, and nitrogen in the pine stand are; 0.90, 0.98, 0.76, 0.98, and 0.88, in oak stand; 0.97, 0.93, 0.92, 0.97, 0.74 and 0.73. 3. Factors which affect the decomposition rate of litter are humus, organic carbon, moisture content, calcium, phosphorus and nitrogen. 4. Among the variables, PH, moisture content and phosphorus under the oak and pine forest showed significant differences in each horizon. 5. C/N ratio of pine stands is higher than that of oak stands studied. 6. The vertical distribution of mineral nutrients is highly related with the amount of humus accumulated on top soil.