Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

이광수와 나쓰메 소세키의 문학교육론이 지닌 근대성 비교연구

권혁건(Kwon,Hyuk-Gun),이호규(Lee,Ho-Gyoo),김주현(Kim,Ju-Hyun) 동북아시아문화학회 2011 동북아 문화연구 Vol.1 No.28

Soseki is representative novelist and theorists of Japanese modern literature, and Lee Gwangsoo (Lee) is known as person who opened doors to Korean modern literature. They are representing not only Korean and Japanese modern literature, but also Oriental modern literature. We focused on the early stages of their literary theories. As well, looked into their arguments based on their ideas of literary education in relation between literature and society. Although Soseki and Lee are both representatives of Korean and Japanese modern literature, we have found their literary theories to have contrasts, as well as undertoned ideal substance. Their findings show identical recognition in defining the workings of human mind as intellect, emotion and volition. Also, their thoughts on the realm of emotion is the characteristic of literature, and explained modern literature by drawing the concepts of rationality and truth. Soseki insisted literary art is not a simple skill; a literary artist could influence others due to their ideals that a literary artist is someone who has the biggest and highest ideals. Lee’s argument resembles Soseki’s argument. Lee contended literary art can be made simply with skill and endeavor. Only highly gifted artist can take charge of a growing self-regulating person who could lead society through literature. Soseki and Lee both, therefore, conclude the Occidental natural science (in other words, education that is logical and substantiate) is modern education, and upcoming Oriental new education need to take after. We found Soseki and Lee have contended education through literature that could produce self-regulating and liberal individuals based on the mentioned Occidental new education.

Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen

Woo, Je Moon,Shin, Da-Yong,Lee, Sung Ju,Joe, Yeonsoo,Zheng, Min,Yim, Jin Ho,Callaway, Zak,Chung, Hun Taeg Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells.</P><P><B>Methods</B></P><P>Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H<SUB>2</SUB>O<SUB>2</SUB>. HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining.</P><P><B>Results</B></P><P>Curcumin had little cytotoxicity at concentrations less than 30 μM, and HO-1 expression was the highest at the 15 μM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H<SUB>2</SUB>O<SUB>2</SUB> through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin’s effect on the reduction of ROS was mediated by the increase in HO-1 expression.</P><P><B>Conclusions</B></P><P>Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.</P>

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.

한국형출혈열 병원체 Hantaan virus에 대한 뇨의 살균작용

이호왕,백낙주,양상기 대한감염학회 1981 감염 Vol.13 No.1

Korean hemorrhagic fever(KHF) reported for the first time in Korea in 1951, althought it had previously been known from both Manchuria and Russia. Since that time it has been known as Korean hemorrhagic fever and has remained endemic near the Demilitarized Zone between North and South Korea. In 1976 and 1978, Lee et al reported the isolation of Hantaan virus, the etiologic agent of KHF, from the patients and Apodemus agrarius coreae collected in the endemic areas of KHF and developed Lee's method of serological diagnosis of KHF. Very recently, Lee et al demonstrated virus excretion in the urine of infected Apodemus agrarius for a long time. The urine from both Apodemus agrarius and susceptible human were examined its effect on the infectivity of Hantaan virus to Apodemus mice. The results are summarized as follows: 1) The urine from Apodemus agrarius rodent, the natural reservoir of Hantaan virus, had higher activity to inactivate the infectivity of Hantaan virus than that of human. 2) The urine from Apodemus agrarius just after sampling was pH 8.3 and it had stronger antiviral activity than the urine adjusted to pH 7.2. 3) pH of human urine just after sampling was 6.1 and this urine decreased 10~100 10? of the virus after 3 hours in room temperature, but the urine with pH 7.2 had no change to infectivity of the virus.

The Identification of Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, Using Macroscopic, Microscopic and Physicochemical Methods

Jee-Hyun Yoon,Ha-Yeong Park,Tae-Ju Kim,Seung-Ho Lee,Jung-Hoon Kim,Guem-San Lee,Hong-Jun Kim,Young-Sung Ju 대한한의학회 2014 대한한의학회지 Vol.35 No.4

Safety of subtotal or total colectomy with primary anastomosis compared to Hartmann procedure for left-sided colon cancer obstruction or perforation

Eun-Do Kim,Jin-Kwon Lee,Jin-Kyu Cho,Jae-Myung Kim,Ji-Ho Park,Ju-Yeon Kim,Sang-Ho Jeong,Young-Tae Ju,Chi-Young Jeong,Eun-Jung Jung,Young-Joon Lee1,Soon-Chan Hong,곽승진 대한종양외과학회 2019 Korean Journal of Clinical Oncology Vol.15 No.2

Purpose: Whether subtotal or total colectomy with primary anastomosis (PA) is safer than Hartmann procedure (HP) for left-sided colon cancer obstruction or perforation remains controversial. The purpose of this study was to compare postoperative morbidity, mortality, and defecation frequency between PA and HP for left-sided colon cancer obstruction or perforation. Methods: This retrospective study enrolled 54 patients from January 2014 to February 2018 who underwent emergency surgery due to left-sided colon cancer obstruction or perforation. Results: PA was carried out in 20 patients while HP was performed for 34 patients. Thirty-day mortality did not show significant difference between the two groups (15.0% vs. 14.7%, P=1.000). No anastomotic leakage occurred in PA group while three (8.8%) cases of stump leakage occurred in HP group. Stoma repair was performed for 13 cases (44.8%) and stoma reformation was performed for one case in HP group (7.7%). Stoma related complications occurred in five cases (17.24%). For patients after stoma repair, defecation frequency at 3 months after operation was 2.91±2.88 times per day in PA group and 2.86±2.63 times per day in HP group. At 1 year after operation, defecation frequency was changed to 1.40±1.12 times per day in PA group and 1.17±0.39 times per day in HP group. Conclusion: Primary ileosigmoid or ileorectal anastomosis for left-sided colon cancer obstruction or perforation is safe, and shows similar outcome of defecation frequency compared to H

ORiginal Article : Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

( Yoon Jeong Choi ),( Nayoung Kim ),( Ju Yup Lee ),( Ryoung Hee Nam ),( Ji Hyung Seo ),( Seonmin Lee ),( Hee Jin Kim ),( Yoon Jin Choi ),( Hye Seung Lee ),( Dong Ho Lee ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-Lcysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods: Sprague- Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanolonly group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor a, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMKS005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. (Gut Liver 2016;10:348- 355)

The Identification of Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, Using Macroscopic, Microscopic and Physicochemical Methods

Yoon, Jee-Hyun,Park, Ha-Yeong,Kim, Tae-Ju,Lee, Seung-Ho,Kim, Jung-Hoon,Lee, Guem-San,Kim, Hong-Jun,Ju, Young-Sung The Society of Korean Medicine 2014 대한한의학회지 Vol.35 No.4

Objectives: This study aimed for establishing the discriminative criteria for Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, which can be confused as 'Mokhyang', because of similar appearances and synonyms. Methods: Morphological characteristics of dried herbal medicines were compared by macroscopic observation. To examine microscopic features of 'Mokhyang', paraffin embedding and the staining by using Ju's method were conducted. Physicochemical experiments were performed using HPLC analysis and antioxidant assay. Results: The types of stem, phyllotaxy and leaf shape were chosen as macroscopic criteria and the size, oil spots, color and root top as well as phloem and central cylinder were compared using microscopic features. The HPLC results showed different amounts of costunolide and dehydrocostuslactone among Aucklandiae Radix, Inulae Radix and Vladimiriae Radix. However, Aristolochiae Radix only contained aristolochic acid. The antioxidant assays also showed that Vladimiriae Radix exhibited strongest antioxidant activity followed by Aucklandiae Radix, Inulae Radix and Aristolochiae Radix. Conclusions: These results demonstrate that macroscopic, microscopic and physicochemical methods would be useful tools for the discrimination of 4 kinds of 'Mokhyang'.

조기위암에서 복강경 보조 위아전절제술과 개복술의 무작위 전향적 연구

이재혁,이주호,서주영 이화여자대학교 의과대학 2003 EMJ (Ewha medical journal) Vol.26 No.2

Methods : Forty-seven patients, endoscopically diagnosed as EGC on antrum and lower body, were included during the period from November 2001 to August 2003. Using a random number table, 23 patients were assigned to open group(group O) and 24 patients to LADG group(group L). Radical distal subtota 1gastrectomy with gastroduodenostomy was performed in all patients. The clinicopathologic findings, postoperative recovery, and morbidity were compared between two groups. Results : Age, sex, body weight, associated disease, history of previous abdominal surgery, location of lesion, size, gross type of EGC, and histologic differentiation were similar in both groups. On permanent pathologic examination, all cases of group O were diagnosed as EGC and in the group L, 21 cases were EGC, 3 cases were advanced cancer. The mean operation time was significantly shorter in the group L, but estimated blood loss and transfusion amount were similar in both groups. The mean postoperative days of first flatus, starting day of diet, postoperative hospital stay were shorter and deration of analgesic administered were lower in group O, but they did not reach statistical significance. The mean numbers of harvested lymph nodes were 38.1 in the group O and 31.8 in the group L, which was not statistically significant(p=0.098). Postoperative pulmonary complication based on chest X-ray occurred more frequently in the group O (p=0.043). There is no recurrence of disease in both groups in follow-ups. Conclusion : LADG has advantage in terms of less phlmonary complications while main-taining the curatility. This is the preliminary result of prospective randomized study and the long-term results should be followed. 고찰 복강경 수술이 점차 발전함에 따라 위장관 질환의 치료에 있어서도 복강경 수술이 점차 중요한 수단으로 자리 잡아 가고 있다. 1991년 일본의 Kitano 등이 조기위암에 대해 림프절 절제술을 포함한 복강경 보조 위점제술을 시행한 이래로 이에 대한 많은 보고들이 발표되고 있으며 최근에는 위전절제술도 복강경 수술로 시행된 예들이 보고되고 있다. 저자들은 199년부터 조기 위암 환자에서 림프절 절제술을 포함한 복강경 보조 위절제술을 도입하여 시행하였으며, 복강경 보조 위 절제술을 받은 군과 개복술을 시행 받은 군을 후향적으로 비교한 연구를 통해 복강경 보조 술식이 개복술과 비교하여 실혈량, 수혈량, 합병증 발생에 차이가 없고, 15개 이상의 림프절 절제가 가능하며, 수술 후 회복이 빠른 것을 보고 한 바 있다. 복강경 대장 절제술에 대해서는 무작위 전향적 연구가 여러 편 보고된 바 있으나 복강경 ?I 위절제술에 대한 무작위 전향적 연구는 2002년 Kitano 등 이 각 군에 14명의 환자를 대상으로 시행하여 발표한 중간 보고가 유일하다. 저자들도 조기위암에서 복강경 복강경 보조 위절제술을 유용성에 대해 보다 객관적인 근거를 제시하고자 무작위 전향적 연구를 시작 하였다. 조기위암은 점막암의 경우 2~4%. 점막하층암의 경우 18~20%에서 위 주위 림프절에 전이가 있으며, 전이된 림프절은 점막암에서는 99%가 제 1군 림프절이지만 점막하층암의 경우 약 5%에서 제2군(대부분 #7, #8, #9)으로 전이된다. 조기위암에서의 이상적인 림프절 절제술의 범위는 아직 논의중에 있지만, 위의 사실은 적어도 점막하층암에 대해서 D1 림프절 절제술은 불충분한 수술임을 시사하며 일본의 위암 권고안에서도 9번 림프절까지의 림프절 절제술을 권하고 있다. 본 연구는 LADG에서는 2군 림프절인 #7, #8,#9,#11,#12a에 대한 림프절 절제술이 시행되었으며 절제된 림프절 개수는 L군에서 31.8±13.5개, O군이 38.1±15.9개로 두 군 모두 평균 30개 이상의 림프절이 절제 되어 충분한 림프절 절제로 판단되었다. 본 연구에서는 수술의 적응증을 내시경적으로 조기위암으로 진단된 경우로 정하였는데 이적응증은 수술 후 진단이 진행 위암으로 판명될 가능성을 배제할 수 없다. 조기 위암의 림프절 전이나 위벽 친윤도를 수술 전에 평가할 수 있는 방법들 중에서 내시경적 초음파의 정확도가 가장 높은 것으로 보고되고 있으나, 아직 이러한 진단 방법으로도 정확도는 70~80%에 머물고 있는 실정이다. 저자들도 일부의 조기위암환자에서 내시경적 초음파를 이용하여 침윤도를 검사하고는 있으나 이 진단 방법의 신뢰성이 아직은 만족할 만 하지 않으므로 이 수술의 적응증을 결정하는 검사로는 사용하지 않고 있다. 본 연구에서 수술 전 조기위암으로 진단된 47명의 환자 중 3명의 환자는 진행위암으로 판명되었다. 현재 진행 위암에도 복강경 수술을 적용한 사례들이 보고되고 잇는데 앞으로 이들 환자들은 진행 위암환자에서의 복강경 수술의 장기적인 추적 결과를 알아보는데 도움이 될 것으로 기대된다. 3명의 진행 위암 환자 중 고유 근육층까지 침범한 2예에서는 림프절 전이가 없었으나 장막층 침범이 있었던 1예에서는 총 38개의 절제된 림프절 중 4번 림프절에 2개의 림프절에 전이가 발견되었다. 그러나 이미 광범위의 림프절 절제술이 시행되었다고 판단하고 전이된 림프절이 제 1군에 국한되어 있었기 때문에 추가적인 림프절 절제술은 불필요하다고 판단하였으며 현재 관심을 가지고 추적 관찰 중이다. 복강경 수술의 가장 큰 장점은 작은 절개창을 이용함으로써 통증에 의한 스트레스를 감소시켜 전신적인 염증반응을 줄임으로써 이로 인한 수술 후 합병증을 감소시키고 회복기간을 단축시킨다는 점이다. 특히 상복부 수술 후 통증은 횡경막의 운동을 억제하여 페기능을 저하시키고 결과적으로 무기폐, 늑막삼출 등의 폐합병증을 유발시킨다고 알려져 있다. Adachi 등은 복강경 보조 위절제술을 받은 환자 군이 수술에 의한 손상이 적고 보다 좋은 영양 상태를 유지 하며 통증이 적고, 장운동의 회복이 빠르고, 재원기간이 짧으면서 근치성에 있어 개복술에 뒤지지 않음을 보고 하였다. 2002년 Kitano등은 최초의 전향적 무작위 연구의 중간 보고를 통해 복강경 보조 위절제술을 받은 환자 군이 수술 후 빠른 회복과 적은 통증, 폐기능 보존의 장점이 있음을 보고 하였다. 본 연구에서도 통계적인 유의성은 얻지 못하였으나 개복군에 비하여 복강경 보조 위절제군에서 수술 후 통중이 적고 회복이 빠르며 재원기간이 짧은 경향을 보였고, 무기폐, 늑막삼출 등이 개복술에 비하여 유의하게 적은 것으로 나타나 복강경 수술이 술 후 합병증 특히 폐 합병증을 줄일 수 있다는 것을 알 수 있었다. 결론 조기위암에서 임파선 절제술을 포함한 복강경 보조 위절제술은 개복술에 근접하는 근치성을 가지며, 통증이 적고 폐 합병증을 줄일 수 있는 장점을 가지고 있다. 이 결과는 현재 진행되고 있는 무작위 전향적 연구의 중간보고로 향후 더 많은 환자에 대한 연구와 재발율과 생존율, 그리고 환자들의 삶의 만족도와 질 향상에 대한 장기 추적 검사가 이루어져야 하겠다.