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      • Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus <i>Aspergillus</i> sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

        Kim, Dong-Cheol,Cho, Kwang-Ho,Ko, Wonmin,Yoon, Chi-Su,Sohn, Jae Hak,Yim, Joung Han,Kim, Youn-Chul,Oh, Hyuncheol MDPI AG 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.4

        <P>In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus <I>Aspergillus</I> sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.</P>

      • 동종 조혈모세포이식 후 발생한 크립토콕쿠스 척추염 1예

        고윤호,임동준,이성수,조유경,이동건,최정현,김유진,민창기,김동욱,박정미,김춘추,신완식 대한감염학회 2001 감염 Vol.33 No.4

        Skeletal cryptococcosis is an uncommon infection. Cryptococcus is a common cause of meningitis and infects 7∼10% of patients with AIDS. As well as AIDS, the infection may be seen in association with leukemia, lymphoma, Hodgkin's disease, sarcoidosis, tuberculosis and diabetes, also in patients on steroid medication. But there is no case report of skeletal cryptococcosis following allogeneic hematopoietic stem cell transplantation. A 40-year-old woman was admitted to the hospital because of low back pain. She had chronic myelogenous leukemia for 2 years and underwent allogeneic hematopoietic stem cell transplantation 8 months ago. She have been treated with steroid and cyclosporine orally because of chronic graft versus host disease. On examination she was afebrile and had posterior lower lumbar tenderness. But, she had no reduced strength of low extremities. Open biopsy was underwent. Histology demonstrated budding, round-to-oval, refractile yeast-like organisms within debris. The results of a lumbar puncture were unremarkable and cerebrospinal fluid culture failed to grow bacteria and yeast. The patient was treated with amphotericin B (1 gram) and AmBisome□ (2.8 gram) over 6 weeks. Three months after cessation of therapy, the patient was doing well.(Korean J Infect Dis 33:298∼301, 2001)

      • 실드터널 시공시의 지표 구조물의 침하 억제 대책에 관한 연구

        임종철,윤이환,박이근,고호성,홍석우 釜山大學校生産技術硏究所 1999 生産技術硏究所論文集 Vol.56 No.-

        연약지반 터널 굴차시 실드공법은 근접 구조물 안전에 유용한 공법이다. 하지만 실드 터널 공법은 터널 주변 지반의 변형을 최소화 할 수 있는 장점을 가지는 반면 테일 보이드(Tail Void)에 그라우트된 주입재가 경화되기 전에 발생하는 지반 변형은 피하기 어렵다. 본 연구에서는 테일 보이드로 인한 인접 구조물의 침하를 억제하는 방법중 하나인 마이크로파일(micropile)의 영향을 모형실험을 통하여 규명하였다. 기초적인 실험 결과로써 마이크로파일 보강시 마이크로파일의 효과적인 설치방향과 침하 억제비를 밝혔다. In soft ground tunneling, shield method is very good for safety of neighboring structures. Although shield tunnel method has the merits to minimize the deformation of ground around tunnel, ground deformations occurred until the material grouted in tail void hardens are inevitable. In this study, the effects of micropile used as one method to restrain the settlement of neighboring structures by the tail void are studied by laboratory model tests. As a basic test result, the effective direction of micropile and the restraint rate of settlement by micropile reinforcement are known.

      • KCI등재

        Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

        Jung Kyung Hee,Kim Sang Eun,Go Han Gyeol,Lee Yun Ji,Park Min Seok,Ko Soyeon,Han Beom Seok,Yoon Young-Chan,Cho Ye Jin,Lee Pureunchowon,Lee Sang-Ho,Kim Kipyo,Hong Soon-Sun 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.6

        According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

      • 당뇨병과 동반된 화농성 간농양의 임상상 및 예후인자

        오은숙,강무일,이원영,오기원,임동준,이소영,이정민,고승현,김성래,안유배,손현식,윤건호,차봉연,이광우,손호영,강성구 대한당뇨병학회 2000 임상당뇨병 Vol.1 No.1

        연구배경: 감염질환은 혈관질환과 함께 당뇨병의 중요한 사망원인의 하나이며, 혈당조절이 불량할수록 감염 빈도가 증가됨은 잘 알려져 있다. 간농양의 발생이 있어서도 당뇨병은 중요한 기저질환 중의 하나이다. 일반적으로 간농양의 가장 흔한 원인균은 Escherichi coli라고 알려져 있으나, 최근 당뇨병을 가진 간농양 환자에서 Klesiella pneumoniae의 검출이 증가되고 있다. 또 최근 연구에 의하면 K.pneumonie가 간농양의 가장 흔한 원인균이며, K. pneumoniae에 의한 간농양은 K.pneumoniae 이외의 균주에 의한 간농양보다 당뇨병과 밀접히 관련되어 있다고 보고된 바 있다. 이에 저자들은 간농양 환자를 대상으로 당뇨병환자의 빈도를 알아보고, 그 원인균 및 특징을 비당뇨병 환자들의 경우와 비교해 보고자 하였다. 방법: 1992년 1월부터 1999년 6월까지 방사선학적 검사 혹은 수술에 의해 간농양이 확인되거나, 경피적 천자나 수술을 통한 배농액 배양, 혹은 혈액 검사에서 원인균이 증명된 182명의 환자를 대상으로 후향적 임상고찰을 실시하였다. 결과: 화농성 농양을 가진 167명의 환자(남:94명, 여:73명)중 당뇨병을 가진 환자는 54명 (남:30명, 여:24명)으로 32.3%를 차지하였다. 환자의 평균나이는 당뇨군에서 62.1 ± 13.4세, 비당뇨군에서는 55.1 ±15.5세로 당뇨군에서 높았으며(p=0.0021), 남녀간의 평균나이 비교 시 두 군 모두 여성의 나이가 의미있게 높았다. 비당뇨군에 비하여 당뇨군의 경우 저알부민혈증의 빈도와 aspartate transaminase가 증가되어있었다. 원인균주는 K. pneumoniae (당뇨군54%, 비당뇨군 39.1%), E. coli(당뇨군 17.5%, 비당뇨군 18.8%), Pseudomonas aeruginosa, Streptococcus viridans, Enterococcus 순이었으며 두 군간의 의미는 차이는 없었으나 K. pneumoniae의 경우 다른 균종에 비해 단독감염의 빈도가 높았다(82.8%). 사망률은 당뇨군에서 16.7%, 비당뇨군에서 7.1%로 당뇨군에서 의미있게 높았으며(p=0.019), 당뇨군에서의 사망환자는 모두 패혈증이 동반되어 있었다. 당뇨환자의 사망군은 생존군에 비해 당뇨병 이환기간이 길고 혼합감염의 빈도가 높았다(p=0.046). 검사실 소견에서는 총 빌리루빈 및 알카리성 포스파타제의 증가가 관찰되어 있었다. 결론: E. coli가 간농양의 주된 원인균이라는 기존 보고와는 달리 당뇨군과 비당뇨군 모두 K. pneumoniae가 간농양의 주된 원인균이었다. 또한 당뇨 유병기간이 길고 당뇨조절이 불량한 환자에서 혼합감염이며 총 빌리루빈 및 알카리성 포스파타제의 증가등과 같은 위험인자가 존재할 경우 사망률이 증가될 수 있으므로 이들 군에서는 적극적인 치료가 필요할 것으로 사료된다. Background: Liver abscesses are commonly associated with underlying disease, particularly diabete mellitus. The number of the liver abscesses caused by Klebslella pneumoniae in diabetic patient has been increased in Korea nowadays. This study was conducted to clarify the clinical presentation and prognostic factors of pyogenic liver abscesses, especially in diabetic patients and to determine the proportion of K. pneunomiae as a pathogen in liver abscess in Korea. Methods: Medical records of 167 patients treated for pyogenic liver abscess from January, 1992 through June, 1999 were reviewed retrospectively in detail. Major Pathogenic organism, clinical manifestations, prognostic factors, the importance of diabetes mellilus as an underlying disease and its effect on clinical features and prognosis were analyzed. Results: Among 167 cases of pyogenic liver abscess, underlying diabetes mellitus was present in 32.3%. The mean age of patients was 62.7 13.4 years in diabetic liver abscess group and 55.1 15.5 years in non-diabetic liver abscess group. Most liver abscesses were cryptogenic in origin or secondary to the billary tree diseases. The clinical presentations among the two groups were not significantly different. When compared to patients without diabetes, patients with diabetes had significantly higher proportions of hypoalbuminemia and elevated aspartate transaminase level. The most common organism of the pyogenic abscess was K. pneumoniae in both groups. Percutaneous drainage of the abscess with appropriate antibiotics was the most commonly used therapeutic modality in liver abscess. The mortality rate of diabetic liver abscess is 16.1 % and 7.1% in nondiabetic liver abscess. Complications, especially septicemla, were found more frequently in patients with diabetes than in patients without diabetes (64.8% vs 28.3%, septicemia : 31.5% vs 9.7%). The factors influencing mortality in the diabetic liver abscess were disease duration, mixed infection, presence of septicemia, elevated bilirubin and alkaline phosphatase. Conclusions: In contrast to prior report that the E. coli was the most common pathogen in liver abscess, we found that K. pneumoniae was the most common organism cultured in liver abscess. Diabetic patients have more complications and higher mortality than patients without diabetes. Early detection and proper treatment are needed to improve the outcome for diabetic patient with liver abscess.

      • SCIEKCI등재

        Docetaxel Monotherapy as Second-Line Treatment for Pretreated Advanced Non-Small Cell Lung Cancer Patients

        ( Yoon Ho Ko ),( Myung Ah Lee ),( Yeong Seon Hong ),( Kyung Shik Lee ),( Hyun Jin Park ),( Ie Ryung Yoo ),( Yeon Sil Kim ),( Young Kyoon Kim ),( Keon Hyun Jo ),( Young Pil Wang ),( Kyo Young Lee ),( J 대한내과학회 2007 The Korean Journal of Internal Medicine Vol.22 No.3

        Background: Second-line chemotherapy offers advanced non-small cell lung cancer (NSCLC) patients a small, but significant increase in survival. Docetaxel is usually administered as a 3-week schedule, yet there is significant toxicity with this therapy. Therefore, a weekly schedule has been explored in several previous trials. In this retrospective study, we compared the efficacy and safety of a weekly schedule and a 3-week schedule of docetaxel monotherapy in a second-line setting. Methods: Docetaxel was administered as 75 mg/m2 on day 1 every 3 weeks or as 37.5 mg/m2 on day 1 and 8 every 3 weeks until disease progression or severe toxicity developed. Results: From October 2003 to March 2006, a total of 37 patients received docetaxel monotherapy and 36 patients could be evaluated. A total of 135 cycles were administered and then evaluated. The median overall survival was 13.3 months (95% confidence interval: 6.3~20.3) for the weekly schedule and 10.7 months (95% confidence interval: 8.3~13.0) for the 3-week schedule (p=0.41). The median time to progression was 3.0 months (95% confidence interval: 1. 9~4.0) and 2.8 months (95% confidence interval: 1.0~4.6), respectively (p=0.41). The response rate was 16.7% for the weekly schedule and 21.1% for the 3-week schedule. The major form of hematologic toxicity was grade 3-4 neutropenia (3-week: 38.9%, weekly: 9.5%). The non-hematologic toxicities were similar between the two schedules. There were no treatment-related deaths. Conclusions: A docetaxel weekly schedule was very tolerable and it had comparable activity to that of the 3-week docetaxel schedule. Considering the efficacy and tolerability, a docetaxel weekly schedule can be an alternative schedule for the standard treatment of NSCLC in a second-line setting.

      • Clinical characteristics and prognostic factors for primary appendiceal carcinoma.

        Ko, Yoon Ho,Park, Se Hoon,Jung, Chan-Kwon,Won, Hye Sung,Hong, Sook Hee,Park, Ji Chan,Roh, Sang Young,Woo, In Sook,Kang, Jin Hyoung,Hong, Young Seon,Byun, Jae Ho Blackwell Pub. Asia 2010 Asia-Pacific journal of clinical oncology Vol.6 No.1

        <P>AIM: Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms. METHODS: We performed a retrospective analysis of patients who had appendectomies between 1991 and 2007 at five centers in South Korea. RESULTS: Overall 55 patients (19 men, 36 women, median age 61 years) were identified. Of these, 37 (67.3%) were mucinous adenocarcinomas, 14 (25.5%) were intestinal-type adenocarcinomas, and four (7.3%) were signet ring cell carcinomas. The distribution of stages was: 26 (47.3%) with localized disease, five (9.1%) with regional disease, and 24 (43.6%) with distant metastatic disease. The overall 3- and 5-year survival rates among all patients were 72.2% and 64.0%, respectively, with 20 deaths during the follow-up period. In a multivariate analysis, high histological grade (hazard ratio [HR]vs low grade 15.7; P = 0.001) and pathological stage (distant vs loco-regional, HR 6.2; P = 0.021) were independent predictors of overall survival. Of the 34 patients who underwent curative resections of primary appendiceal carcinomas, the 3- and 5-year disease-free survival rates were 66.4% and 53.3%, respectively. The recurrence rate was higher in patients with regional lymph node metastasis (HR vs node negative disease 23.4; P = 0.005) and high-grade tumors (HR vs low grade 6.3; P = 0.029). Additionally, a right hemicolectomy reduced the risk of recurrence (HR vs lesser procedures 0.05; P = 0.005). CONCLUSION: High tumor grade and advanced stage were significantly predictive of poor survival outcome in patients with primary appendiceal carcinomas.</P>

      • KCI등재

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