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      • HMG-CoA 환원효소 억제제에 의한 ICAM-1 유전자의 발현조절

        김현진,정효균,홍우정,김군순,조영석,김도희,채수흥,구본정,송민호,노흥규,김영건 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

        Background : ICAM-1 act as one of major adhesion molecules in the atherosclerotic lesion. ICAM-1 expression is mainly regulated at the level of transcription and depend on IFN-γ signal transduction pathway in which the STAT1 transcrption factor is a critical intermediate. IFN-γreceptor not only initiates tyrosine 701 phosphorylation of STAT1 by Jak1 and Jak2, but also phosphorylates serine 727 through the activation of Raf-1/MAP kinases. HMG-CoA reductase inhibitors have anti-atherosclertic effects, beyond normalization of hypercholesterolemia, by directly acting on endothelial cells, macrophages and vascular smooth muscle cells. HMG-CoA reductase inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibition posttranslational farnesylation and geranyl-geranylation processing of small GTP-binding preoteins and inhibition of normal signaling activities. Method : We made several 5'-deletion constructs of rat ICAM-1 promoter and analyzed the promoter activities by measuring the luciferase activity after transfection into ECV304 cells and smooth muscle cells. We checked the level of total and phosphorylated STAT1 protein by immunoblot analysis using specific antibodies. Results : Lovastatin inhibits IFN-γ-induced ICAM-1 gene expression in the ECV304cell. The cells pretreated with PD98059, MEKK inhibitor showed significantly low ICAM-1 RNA induction with IFN-γ stimulatio. IFN-γ induced phosphorylation of tyrosine 701 was not significantly changed by the pretreatment of lovastatin. But lovastatin suppresses IFN-γ-induced phosphorylation of ERK1/ERK2 which are responsible for the seine 727 phosphorylation in STAT1. Conclusion : We showed that HMG-CoA reductase inhibitors, lovastatin, suppresses IFN-γ mediated ICAM-1 gene expression through the inhibition of transcription. HMG-CoA reductase inhibitor suppresses IFN-γ-induced phosphorylation of serine 727 in STAT1 through the modulation of MAP kinases.

      • KCI등재

        흰쥐의 방사선 피폭후 생물학적 지표로서의 혈액효소

        김진규,김상복,김국찬,천기정,김인규,박효국,이강석 대한방사선 방어학회 1993 방사선방어학회지 Vol.18 No.2

        생물학적 선량평가를 위한 생화학적 지표 연구로서 흰쥐 혈액내 효소활성도의 변화를 조사한 결과는 다음과 같다. 1) Alkaline phosphatase 활성도는 0.1, 0.25, 0.5, 2, 4 Gy의 방사선 조사후 24시간까지 혈액내 활성도가 증가하였고 72시간 경과시에는 대조군과 비슷한 활성도를 보였다. Creatine kinase는 2, 4 Gy 방사선 조사후 혈액내에서 활성도에서 활성도가 72시간까지 증가하였으나 0.1, 0.25Gy, 0.5 Gy 방사선 조사시에는 커다란 변화를 보이지 않았다. 2) Malate dehydrogenase 활성도는 0.1, 0.25, 0.5 Gy 방사선 조사시에는 커다란 변화가 없었으며 lactate dehydrogenase는 방사선 조사후 활성도가 감소하였다. 3) GOT의 활성도는 선량률 0.1Gy/min.로 0.1, 0.25, 0.5, 2, 4 Gy 조사후에는 어떠한 변화도 없었으며 선량률 0.5 Gy/sec.로 0.5, 1, 1.5, 2, 3, 5, 7 Gy로 조사후에는 증가현상을 보이고 있다. Acid phosphatase 활성도는 상기의 어떠한 선량에서도 나타나지 않고 있다. 잠재적으로 이러한 효소들은 방사선 피폭의 지표물질로 사용될 수 있으며 생화학적 지식과 기술을 이용한 좀더 나은 지표물질을 찾기 위하여 계속적인 조사가 필요하다. Enzyme activity changes in rat blood as biochemical indicator useful for evaluating exposure dose were experimentally studied. The experimental results obtained are as follows: 1) Alkaline phosphatase activities increased in the blood serum until 24 hours after 0.1, 0.25, 0.5, 2 and 4 Gy irradiation and its activities returned mormal condition after 72 hours of post-irradiation. Creatine kinase activities increased in the blood serum until 72 hours after 2 and 4 Gy irradiation but any significant activity changes were not detected after 0.1, 0.25 Gy irradiation. 2) Malate dehydrogenase activities did not reveal available changes changes after 0.1, 0.25, 0.5 Gy irradiation and lactate dehydrogenase activities decreased in the blood serum after 0.1, 0.25, 0.5 Gy irradiation. 3) Glutamate oxaloacetate transaminase activity changes were detected in the blood serum after 0.1, 0.25, 0.5, 2, 4 Gy(0.1 Gy/min.) and GOT activities increased after 0.5, 1, 1.5, 2, 3, 5, 7 Gy(0.5 Gy/sec.). Any acid phosphatase activities were detected in the blood serum after 0.1, 0.25, 0.5, 2, 4 Gy(0.1 Gy/min.) and 0.5, 1, 1.5, 2, 3, 5, 7 Gy(0.5 Gy/sec.) irradiation. Potentially some of these enzymes can be used as indicator protein for radiation injury. Futher investigation is needed to find better biochemical indicatiors utilizing recent knowledge and techniques of biochemistry.

      • KCI등재

        Exploring potential biomarker responses to lithium in Daphnia magna from the perspectives of function and signaling networks

        Hyo Jeong Kim1,2,Jun Hyuek Yang,Hyun Soo Kim,Yeo Jin Kim,Wonhee Jang,Young Rok Seo,W. Jang,Y. R. Seo 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.1

        I ntensive usage of electronic appliances containing lithium batteries causes an accumulation of e-trash. Environmental exposure to lithium batteries contaminates ecosystems. In air and water, the batteries form lithium hydroxide (LiOH) on their surfaces. LiOH enters the aquatic environment and contaminates the aquatic ecosystem by being absorbed into biological organisms. In this study, in order to identify meaningful potential biomarkers that appear in response to lithium, we measured significantly up- and down-regulated genes after LiOH exposure by conducting a microarray. In addition, we explored the functions of differentially expressed daphnia genes, and we conducted a comparative analysis in other species, Daphnia spp. to humans, then analyzed the signaling pathways using the human gene set derived from daphnia sequences that are differentially expressed in response to LiOH using the NCBI-BLAST tool and Pathway studio. As a result, we identified signaling pathways and suggested several potential biomarkers that are up- or down-regulated in response to lithium. This study may contribute to the development of a biomonitoring system which can detect the ecotoxicity of lithium. Furthermore, lithium toxicity in humans can be predicted, so the study may also provide potential biomarkers of lithium exposure in humans.

      • Risperidone 조기 중단군 및 장기 유지군의 임상적 특성 비교

        김광수,박원명,전태연,배치운,김대진,백인호,이철,김정수,한상익,최보문,장계호,고효진 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.3

        연구목적 : Risperidone 투여후 조기 중단한 환자들과 장기적으로 계속 risperidone을 복용하고 있는 환자의 임상적 특성을 평가하고 나아가 risperidone장기 유지와 조기 중단의 요인을 분석하고 정신병리가 약물 투여에 미치는 영향을 조사하고자 하였다. 방 법 : 연구 대상자는 1996년 1월부터 1996년 12월까지 가톨릭대학교 의과대학 부속 8개 병원 정신과에서 risperidone을 투여 시작한 환자 580명중 DSM-IV기준에 의해 정신분열병으로 진단받고 투여 기간이 6개월 미만(조기 중단군)이거나 2년 이상(장기 유지군)을 경과하였으며 의무기록의 누락이 없는 210명을 선정하였다. 두 군간 임상적 특성을 조사하기 위하여 인구학적 변인, 정신병리학적 변인, 약물 투여기록 및 부작용 등을 과거 의무기록을 근거로 평가하였다. 결 과 : 대상환자 210명 중 조기 중단군이 67명(31.9%)이었고 장기 유지군은 143명(68.1%)이었으며 두 군간 인구학적 변인과 정신병리학적 변인에 따른 특징에는 두 군간 차이가 없었다. 두 군간 risperidone의 시작 용량과 변인과 정신병리학적 변인에 따른 특징에는 두 군간 차이가 없었다. 두 군간 risperidone의 시작 용량과 최대 용량은 유의한 차이가 없었으나 유지용량은 조기 중단군에서 4.49(±1.44)mg,장기 유지군에서 3.67(±1.50)mg으로 유의한 차이가 있었다(t=3.698, p<0.05). 또한, 이전 항정신병약물의 사용 기왕력 변인에서 조기 중단군은 기왕력이 없는 환자가 39명(58.2%), 고역가 항정신병약물을 사용한 기왕력이 있는 환자는 27명(40.3%), 저역가 항정신병약물을 사용한 기왕력이 있는 환자는 1명(1.5%)이었고, 장기 유지군은 기왕력이 없는 환자가 58명(40.6%), 고역가 항정신병약물을 사용한 기왕력이 있는 환자는 77명(53.8%), 저역가 항정신병약물을 사용한 기왕력이 있는 환자는 8명(5.6%)으로 유의한 차이가 있었다.(x²=6.559, df-=2, p<0.05). 결 론 : 본 연구결과에 의하면 가급적 환자 상태에 따라 낮은 최적 치료 용량을 투여하는 것이 장기잔의 투여를 바람직한 것으로 생각된다. 본 연구와 같은 대규모의 후향적 자연적 연구는 일반 실제 진료에서 risperidone의 효과 및 기타 다른 측면에서의 유용한 정보를 얻을 것으로 기대된다. Objective : This retrospective naturalistic study was designed to compare the clinical characteristics including psychopathology of two groups of patients, long-term maintenance group and short-term drop-out group, who were taking risperidone. Method : Datas were collected for 210 schizophrenic patients with complete medical records among 580 patients who were enrolled with risperidone administration from January 1996 to December 1996 in 8 affiliated hospital of the Catholic University. The short-term drop-out patients group were assigned to whom treatment period was less than 6 month, and the long-term maintained patients group, treatment period was more than 2 years. We assessed demographics, psychopathology, and other variables related with medication based on past medical records. Results : Among subjects of 210, short-term drop-out patients group were 67(31.9%) and long-term maintained patients group were 143(68.1%). Demographics and psychopathology were not significantly different between two groups. The stating and maximal dosage of risperidone was not significantly different between two groups but the maintenance dosage of risperidone was lower in long-term medicated patients group than short-term drop-out patients group(t=3.698, p<0.05). Additionally, the result of this study showed differences in experiences of past antipsychotic use as following. The number of no previous use of antipsychotic was 39(58.2%), the number of high potency amtipsychotic use was 27(40.3%), and the number of no previous use of antipsychotic was 58(40.6%), the number of high potency ntipsychotic use was 77(53.8%), the number of low potency antipsychotic use was8(5.6%) in long-term maintained group.(x²=6.559, df-=2, p<0.05). Conclusions : According to these results, administration of low therapeutic dosage should be recommended for long-term maintenance as if possible. Multi-center based retrospective naturalistic study like this would be useful for getting informations about efficacy and some other aspects of antipsychotic administration in practial field.

      • Bupivacaine과 ropivacaine이 Xenopus oocyte에 발현된 HERG 전류에 미치는 영향

        김국성,이규승,김효신,손숙진,이상도,김광진,전병화,김윤희,박진봉 충남대학교 의과대학 의학연구소 2003 충남의대잡지 Vol.30 No.1

        Bupivacaine is an amide-type local anesthetic widely used for regional anesthesia. Ropivacaine is developed as a less cardiotoxic alternatives to bupivacaine. In the present study, we have analyzed the effects of bupivacaine and ropivacaine on HERG currents expressed in Xenopus oocytes. Bupivacaine and ropivacaine(3∼1,000μM) blocked HERG currents in a concentration dependent manner. EC_(50) was 26.1±3.1μM(n_(R) 0.65±0.04) and 43.5±7.9μM(n_(H) 0.99±0.13) in bupivacaine and ropivacaine, respectively. Bupivacaine and ropivacaine did not affect the activation and deactivation kinetics of HERG channels. However, the drugs decreased the slope conductance measured from fully activated current-voltage relationship curves. These results suggest that bupivacaine and ropivacaine have a similarinhibitory effect on HERG channels, which could be a possible cellular mechanism of LQT or ventricular arrythmia by the drugs.

      • KCI등재
      • KCI등재

        Molecular analysis of TMC1 gene in the Korean patients with nonsyndromic hearing loss

        Hyo‐Kyeong Kim,Yee Hyuk Kim,사공보름,권태준,오세경,Hye‐Jin Lee,Kyu‐Yup Lee,이상흔,김언경 한국유전학회 2011 Genes & Genomics Vol.33 No.2

        Hereditary nonsyndromic hearing loss (NSHL) is a highly heterogeneous disorder in humans. Mutations of the transmembrane channel‐like (TMC1) gene have been identified as the genetic cause for both autosomal recessive (DFNB7/11)and autosomal dominant (DFNA36) nonsyndromic hearing loss. To evaluate the spectrum and frequency of mutation(s)caused by TMC1 gene in the Korean population, we have performed sequencing analysis of the PCR products amplified from genomic DNA of each proband in 193 unrelated families showing 30 autosomal dominant and 163 autosomal recessive inheritance patterns. As a result, we identified eight different novel sequence variations for the first time in this study,respectively. However, none of these showed co‐segregation of phenotype in the families. Therefore, our study suggests that the TMC1 gene is not the cause of nonsyndromic hearing loss in the Korean population.

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