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Proton Pump Inhibitors의 작용기전과 사용법
설상영 ( Sang Yong Seol ) 대한소화기학회 2006 대한소화기학회지 Vol.48 No.1
Proton pump inhibitors (PPIs) are widely used in clinical practice from early 1990s for the treatment of acid-related diseases. PPIs are superior to histamine2-receptor antagonists or anticholinergic agents. These drugs have proven to be effective, safe and well-tolerated during the past two decades. This brief review presents the pharmacodynamics and pharmacokinetics of PPIs and presents clincal applications of the drugs in acid-related diseases. (Korean J Gastroenterol 2006;48:4-8)
Anisakis Type I 유충에 의한 위 아니사키스증 20예
설상영(Sang Yong Seol),옥승철(Sung Cheul Ok),표지수(Ji Soo Pyo),김인호(In Ho Kim),이상혁(Sang Hyuk Lee),정정명(Jung Myung Chung),최하진(Ha Jin Choi),정승진(Seung Jin Jeong),손운목(Woon Mok Sohn) 대한소화기학회 1994 대한소화기학회지 Vol.26 No.1
N/A Twenty cases of the gastric anisakiasis caused by Anisakis type I larva were found by endo- scopic examination during the period from Sep., 1990 to Oct., 1993 in Pusan. The patients chiefly complained of epigastric pain, nausea and vomiting and recalled they had eaten raw flesh of marine fishes. Followings are the summarized clinical features of cases and the mor- phological characteristics of worms detected. Of 20 cases, the sex ratio of male to female was I to 1.5. In terms of age group, the highest rate of incidence was seen at 30's. A total 13 cases(65. 0%) were infected in the winter season, 5 and 2 ones were in the autumn and spring. The main source of infection might be Astroconger myriaster based on the past history of cases. The onset of symptom after eating causative fish occurred within 12 hours in 15 cases(75.0%). The epigastric pain was experienced in all cases. The most frequently detected site of worm in the stomach was the greater curvature(65.0%) of the body. The endoscopical findings of the gastric mucosa adjacent to worms were edematous, sometimes erosive and hemorrhagic. A total 18 out of 22 detected woms were the 3rd stage larvae of Anisakis type I and the others were the 4th stage ones. From the above results, it was confirmed that numerous cases com- plained the epigastric pain after eating raw fish caused by Anisakis type I larva.(Korean J Gastroenterol 1994; 26 : 1 7-24)
이상혁(Sang Hyuk Lee),강호규(Ho Kyu Kang),이인희(In Hee Lee),황문수(Moon Soo Hwang),김두일(Doo Ill Kim),설상영(Sang Yong Seol),정정명(Jung Myeng Chung),최하진(Ha Jin Choi) 대한내과학회 1991 대한내과학회지 Vol.40 No.6
Benign solitary neurilemoma of the retroperitoneum is a rare disease of nerve sheath origin. A 61-year-old female patient was admitted to our hospital for a huge palpable abdominal mass. Abdominal ultrasonography and CT scan revealed a cystic tumor in the retroperitoneum. On exploratory laparotomy, this mass turned out to be an infant-head sized mass of the retroperitoneum. The mass was excised surgicaliy in an encapsulated state. Histological section revealed a typical neurilemoma.
치료 전 바이러스 농도가 낮고 조기바이러스 반응이 있는 유전자 1형 만성 C형간염은 24주 페그인터페론과 리바비린 치료도 가능할 수 있다
문성수 ( Sung Soo Moon ),강현구 ( Hyoun Gu Kang ),서정아 ( Jeong Ah Seo ),정은욱 ( Eun Uk Jung ),이상헌 ( Sang Heon Lee ),박성재 ( Sung Jae Park ),이연재 ( Youn Jae Lee ),설상영 ( Sang Yong Seol ) 대한소화기학회 2010 대한소화기학회지 Vol.56 No.1
Background/Aims: The standard treatment for chronic hepatitis C infected with hepatitis C virus (HCV) genotype 1 is a combination of pegylated interferon alfa and ribavirin over a 48 weeks period. It is unclear if 24 weeks treatment is possible for patients showing a rapid virological response (RVR) without compromising the sustained virological response (SVR) in Korea. Methods: Between June 2005 and September 2008, among patients chronically infected with the HCV genotype 1 who were treated with pegylated interferon alfa subcutaneously once weekly plus ribavirin based on body weight, 55 patients who had low pretreatment viral load (<600,000 IU/mL) and RVR were enrolled. A total of 55 patients were divided into 24 weeks treatment group (n=29) and the standard treatment group (n=26). The HCV RNA was quantitatively assessed before treatment, and after 12 weeks of treatment, and also qualitatively assessed after 4 weeks of treatment, at end of treatment (24 weeks), and 24 weeks after end of treatment. RVR was defined as undetectable HCV RNA at the 4 weeks of treatment. Results: Among the 55 patients, SVR was achieved in 100% (29/29) of the patients in 24 weeks treatment and 96.2% (25/26) of the patients in the standard treatment (p=0.473). Conclusions: HCV genotype 1 infected patients with a low baseline HCV RNA concentration who become HCV RNA negative at week 4 may be treated for 24 weeks without compromising sustained virlolgical response. However, an additional trial will be needed to optimize the treatment duration. (Korean J Gastroenterol 2010;56:33-38)
B형 간염바이러스 중합효소의 역전사효소 활성을 억제하는 인간 단세포군 항체
박성재 ( Sung Jae Park ),설상영 ( Sang Yong Seol ),지삼룡 ( Sam Ryong Jee ),박은택 ( Eun Taik Park ),이연재 ( Youn Jae Lee ),이상혁 ( Sang Hyuk Lee ),정정명 ( Jung Myung Chung ),조현대 ( Hyun Dae Cho ),정영주 ( Young Ju Jeong ) 대한소화기학회 2007 대한소화기학회지 Vol.49 No.2
목적: 간경변과 간암의 주 원인 중 하나인 B형 간염바이러스(hepatitis B virus, HBV)에 대한 새로운 치료법의 개발의 일환으로 phage display 기법을 이용하여 바이러스 복제에 있어 중요한 P 단백의 역전사효소 활성을 억제하는 인간 단세포군 항체를 제작하여 protein based 유전자 치료 가능성을 분석하고자 하였다. 대상 및 방법: HBV P 단백의 역전사효소 기능 부위인 RT/POL 기능 부위를 pMAL-C 벡터에 클로닝하고 maltose binding protein과 융합 단백의 형태로 재조합 단백으로 발현시켰다. 1.1×10(10)의 인체 single chain Fv phage antibody library를 사용하여 RT/POL 재조합 단백에 대한 항체를 BIAcore로 선택하였다. 선택된 항체의 역전사효소, RNA-dependent DNA 중합효소 기능 정도를 분석하였으며 BIAcore로 항원에 대한 친화도를 그리고 염기서열 분석을 통하여 항원 결정 부위를 확인하였다. 결과: 대장균에서 발현 정제된 RT/POL 기능 부위 재조합 단백은 역전사효소 활성을 유지하고 있었으며, 1μg의 재조합 단백은 5 unit의 MMLV 역전사효소와 동일한 효소 활성을 가지고 있었다. BIAcore를 이용한 RT/POL에 대한 항체의 선택으로 POL-A5, POL-B8 그리고 POL-B12의 3개 클론을 확보하였다. 선택된 클론들의 역전사효소 활성 억제능은 각각 82- 52%였으며, 항원에 대한 친화도는 8.15×10(-8) M to 1.75×10(-6) M이었다. 결론: 이번 연구를 통하여 제작된 인간 단세포군 항체는 항원에 대한 친화도가 낮았으나 in vitro에서 효과적으로 역전사효소 활성을 억제하여 protein based gene therapy로서 세포 내 항체로 발현한다면 HBV P 단백의 기능을 억제하여 바이러스의 복제를 억제할 것이다. Background/Aims: To develop a novel treatment method for hepatitis B virus (HBV) infection, we aimed to make a human monoclonal antibody inhibiting reverse transcriptase (RT) activity of P protein which was important in HBV replication by using phage display technique. Therefore, we analysed the usability of human monoclonal antibody as a protein based gene therapy. Methods: Reverse transcriptase/polymerase (RT/POL) functional motif of P protein of HBV was cloned in pMAL-c vector and expressed as maltose binding fusion protein form. The RT/POL recombinant protein (pMRT/POL) was purified by amylose resin column. Using human single chain Fv phage antibody library with 1.1×10(10) size, human antibody against pMRT/POL was selected with BIAcore panning. Selected antibody fragments were analyzed for the activity of RT inhibition. Finally, they were analyzed for the affinity with BIAcore and the complementarity determining regions with nucleotide sequencing. Results: pMRT/POL recombinant protein expressed in E. coli showed RT activity, 1㎍ of recombinant protein had an activity equivalent to 5 unit of MMLV RT. By BIAcore panning, we could select 3 clones; POL-A5, POL-B8 and POL-B12. Each clone`s RT inhibiting activity were 52-82%, affinity against antigen were 8.15×10(-8) M to 1.75×10(-6) M. Conclusions: Human monoclonal antibodies produced in this study showed low affinity, but efficiently inhibited the activity of RT in vitro. If POL-A5, POL-B8, and POL-B12 can be converted to intracellular antibody form, it can be used for protein-based gene therapy by inhibiting the replication through the neutralization of polymerase protein of HBV. (Korean J Gastroenterol 2007;49:85-92)
Random peptide library를 이용한 C형 간염바이러스 E2 단백질 세포막 수용체의 peptide mimotope 규명
이인희,백재은,설상영,석대현,박세광,최인학,Lee, In-Hee,Paik, Jae-Eun,Seol, Sang-Yong,Seog, Dae-Hyun,Park, Sae-Gwang,Choi, In-Hak 대한면역학회 2001 Immune Network Vol.1 No.1
Background: Hepatitis C virus(HCV), a family of Flaviviridae, has a host cell-derived envelope containing a positive-stranded RNA genome, and has been known as the maj or etiological agent for chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. There remains a need to dissect a molecular mechanism of pathogenesis for the development of therapeutic and effective preventive measure for HCV. Identification of cellular receptor is of central importance not only to understand the viral pathogenesis, but also to exploit strategies for prevention of HCV. This study was aimed at identifying peptide mimotopes inhibiting the binding of E2 protein of HCV to MOLT-4 cell. Methods: In this study, phage peptide library displaying a random peptides consisting of 7 or 12 random peptides was employed in order to pan against E2 protein. Free HCV particles were separated from the immune complex forms by immunoprecipitation using anti-human IgG antibody, and used for HCV-capture ELISA. To identify the peptides inhibiting E2-binding to MOLT-4 cells, E2 protein was subj ect to bind to MOLT-4 cells under the competition with phage peptides. Results: Several phage peptides were selected for their specific binding to E2 protein, which showed the conserved sequence of SHFWRAP from 3 different peptide sequences. They were also able to recognize the HCV particles in the sera of HCV patients captured by monoclonal antibody against E2 protein. Two of them, showing peptide sequence of HLGPWMSHWFQR and WAPPLERSSLFY respectively, were revealed to inhibit the binding of E2 protein to MOLT-4 cell efficiently in dose dependent mode. However, few membrane-associated receptor candidates were seen using Fasta3 programe for homology search with these peptides. Conclusion: Phage peptides containing HLGPWMSHWFQR and WAPPLERSSLFY respectively, showed the inhibition of E2-binding to MOLT-4 cells. However, they did not reveal any homologues to cellular receptors from GenBank database. In further study, cellular receptor could be identified through the screening of cDNA library from MOLT-4 or hepatocytes using antibodies against these peptide mimotopes.