Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

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>

Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

선택적 후근절제술의 수술중 근전도 감시방법과 치료효과

김형일,김연희,김완호,김근수,김동찬 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.10

Selective posterior rhizotomy(SPR) has been known to reduce the spasticity as well as to improve the quality of life in patients with intractable spasticity. Twenty patients underwent SPR under intraoperative electrophysiological monitoring(IOM). Fifty-two percent of sacrolumbar rootlet were cut after electrical stimulation. Eighteen patients(90%) with spastic type of cerebral palsy showed marked reduction of spasticity and functional improvement without any complication. The patients who did not respond to SRP had mixed types of spasticity. IOM facilitate the selection of pathological rootlets regardless of anaesthetic level. intensity of electrical stimulation, and individual variability of responses. It is concluded that careful selection of surgical candidates and of pathological rootlets under IOM are important to reduce the spasticity. thereby to obtain a better outcome.

흰쥐의 원위콩팥단위내 칼슘결합단백질 (calbindin-D28k)에 관한 면역세포화학적 연구

김영희,김완영,김인범,한승호,오수자,차정호,김진 대한해부학회 1997 Anatomy & Cell Biology Vol.30 No.6

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

불응성 자가면역질환에서의 자가조혈모세포이식

민도준,양동원,민창기,김완욱,이상헌,박성환,김동욱,이종욱,조철수,민우성,김범생,김호연,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 기존의 치료에 불응하고 예후가 불량한 자가면역질환 환자들에게 최근 고용량 면역억제 및 조혈모 세포이식이 새로운 치료방법으로 대두되고 있다. 저자들은 다발성 경화증(multiple sclerosis, MS) 및 류마티스 관절염(rheumatoid arthritis, RA) 등 2명의 자가면역질환 환자들에서 자가조혈모세포 이식을 시행하였다. 방법: 말초혈액 조혈모세포 가동화를 위하여 cyclophosphamide (4 g/㎡) 및 granulocyte colony stimulating factor (10 g/kg/day)를 투여하였고, CD34+ 세포를 분리·채집 하였다, 이식 전처치로 MS 환자에서 BEAM 및 antihymocyte globulin (ATG) (3.75 mg/kg), RA 환자에서 fludarabine (180 mg/㎡), ATG (10 mg/kg)와 busulfan (8 mg/kg)을 투여하였다. 결과: 호중구 수가 500/㎕ 이상으로 회복되는 기간은 MS 환자에서 9일, RA 환자에서 15일이었다. 혈소판이 20.000/㎕ 이상으로 회복되는 가간은 RA 환자에서 9일 이었고, MS 환자에서는 혈소판 감소증이 발생하지 않았다. 비혈액학적 독성으로 MS 환자에서 WHO 1도의 오심 및 점막염이 관찰되었다. MS 환자는 이식 6개월 후까지 시력감소가 남아있었으나, 이식전에 관찰되던 감각이상 및 운동장애 등의 신경학적 이상 소견은 더 이상 관찰되지 않았다. RA 환자는 이식 1개월 후 관절 증상 및 검사소견의 호전을 보였다. 결론: 불응성 자가면역질환 환자에서 고용량 면역억제 및 조혈모세포이식은 적은 독성으로 높은 치료효과를 기대할수 있으며, 향후 이 시술의 임상적 의의를 규명하기 위하여 전향적이고 장기적인 연구가 필요할 것으로 사료된다. Background: High-dose immunosuppressive therapy followed by autologous hemathpoietic stem cell transplantation (HSCT) has been proposed as a new approach to treat severe, refractory autoimmune diseases. We describe two patients with refractory autoimmune diseases (one multiple sclerosis 〔MS〕and one rheumatoid arthritis〔RA〕) who underwent T-cell-depleted autologous peripheral bleed stem cell transplantation for the first time in Korea. Methods: We mobilized autologous stem cells with cyclophisphamide (4 g/㎡) and granulocyte colony-stimulating factor (10 ㎍/kg/day). Stem cells were enriched ex vivo using CD34-positive immunoselection and reinfused after high-dose chemotherapy with BEAM and antithymocyte globulin (ATG) (3.75 mg/kg) in MS, or fludarabine (180 mg/㎡), ATG (10 mg/kg) and busulfan (8 mg/kg) in RA. Results: The engraftment with an absolute nerutrophil count greater than 500㎕ occurred on day 9 in MS and 15 in RA, respectively. The time to nontransfused platelet count greater than 2.000/㎕ was 9 day in RA. MS patient did not show ant episode of thrombocytopenia. Regimen-related non-hematopoietic toxicity was minimal. For 6 months since HSCT, them patient with MS had been free from previously existed sensory and motor abnormalities except decreased visual acuity. Then patient with RA and only one tender joint and two mildly swollen joints with improvement in laboratory parameters at one month after HSCT. Conclusion: These results underscore the feasibility and potential efficacy of intensive immunosuppression followed by autologous HSCT for treatment of intractable autoimmune diseases. The durability of remission, however, remains to be clarified.

조혈모세포이식 후 발생한 주폐포자층 폐렴에 대한 고찰

주지현,최정현,이동건,백지연,고윤호,이혜정,김세희,신호진,박윤희,박지영,김유진,신완식,김춘추 대한감염학회 2001 감염 Vol.33 No.4

Background : Pneumocytitis cainii pneumonia (PCP) can occur in immunocompromised hosts especially such as AIDS or cancer patients. Although recent research had focused on PCP in AIDS patients, few studies have described the clinical presentations of PCP in recipients of stem cell transplantation (SCT). We evaluated the clinical manifestations of PCP in SCT patients admitted at St. Mary's hospital, Seoul, Korea. Methods : The medical records of 17 PCP patients undergoing SCT between Feb. 1998 and Feb. 2000 were reviewed. The diagnosis of PCP was confirmed through the demonstration of Pneumocytitis cainii via either cytology of brochoalveolar lavage (BAL) or histological technique of lung biopsy. CMV disease and CMV infection were confirmed by BAL culture and antigenemia respectively . Results : Seventeen patients were all recipients of allogeneic SCT and 7 of 17 patients were performed non-sibling SCT. Patients presented with symptoms including brief period (4 ∼23 days) of fever (76%), dyspnea (70%), cough (64%), and signs such as rare(58.8%), Sixteen patients (94%) had been receiving immunosuppressive agent such as cyclosporine A (64%) or Fk506 (35%) without PCP prophylaxis. Eleven patients (64%) were treated with corticosteroid with mean dose of 16 mg/day prednisolone and mean duration of 4.6 months after post-SCT period. Twelve patients were co-infected with CMV. Another co-infected miCroorganisms were Pseudomonas aeruginosa, Mycobacterium tuberculosis, herpes simplex virus, parainfluenza virus, Average duration of treatment with trimethoprim-sulfamethoxazole (TMP/SMX) was 21 ±9 days. Four patients died, and three of them were related with PCP. Conclusion : PCP developed frequently in patients who were taking immunosuppressive drug due to graft versus host disease or were not taking TMP/SMX prophylaxis. High risk patients showing fever, cough, or dyspnea should be considered to take early bronchoscopic intervention for detection of PCP. When treat for PCP, it also be considered to the possibility of coinfection such as CMV. (Korean J Infect Dis 33:273∼279, 2001)

생물 실험 지도에 있어서 가설 검증 수업모형의 적용 효과

김광수,정완호 한국교원대학교 과학교육연구소 1996 청람과학교육연구논총 Vol.6 No.1

Improving of scientific inquiring ability is the major goal of current science curriculum, and the 6th science curriculum. But science educators consider that the existing textbooks and teaching manuals are insufficient to achieve this goal. For science teachers at teaching site to guide students efficiently in research work, development of teaching-learning programs is urgently demanded. Hypothesis Verification Learning Model(HVLM) was applied to classroom situation to improve ability of scientific inquiry in experiment teaching of middle school biology. The effects of the model were analyzed to suggest some approach method to reach the goal of science education in this study. The major results of this study are as following: 1. The students and teachers responded positively on this new learning model. an students were willing to participate in biology experiment and they said that to know what was unknown to them while exchanging ideas and opinions through the discussion, It was hard for teachers to instruct at the first time and it took much time for them to arrange materials ready, but it turned to be easier as time went on. 2. In science process skills, there was no significant difference statistically by new leaning model. Only the formulating a generalization or model showed significant difference statistically between the two groups. 3. For scientific attitude, experimental group did not show significant difference statistically between the two groups, but the experimental group showed statistically more significant positiveness in all areas afterwards than before. 4. In science achievement test, there was significantly higher than the control group. It is also analyzed that they remember the experiments in courses and results they planned and performed by themselves longer than these guided by teachers.

원형분극 마이크로스트립 배열 안테나의 소형화 연구

김완호,황인진,정봉식 東亞大學校附設 情報技術硏究所 2004 情報技術硏究所論文誌 Vol.12 No.1

In this paper the compact microstrip array antenna with CP(circularly polarized) radiation for GPS(Global Positioning System) is designed. the compact operation of microstrip antenna is obtained by inserting suitable slits in the radiating patch, and CP radiation by giving the unequal length of two pairs of slits, which splits the resonant mode of interest into two orthogonal near degerate modes. Feed network of array antenna is made by using a two-layer structure and via connection probe. By numerical and experimental results, the patch size of compact CP microstrip antenna is reduced about 40% than conventional one.