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Biological Effect of Metronidazole Resistance in Helicobacter Pylori
이진혁,이선미,남원희,김은실,김진호,강호영,정진용,Lee Gin Hyug,Lee Sun-Mi,Nam Won-Hee,Kim Eun Sil,Kim Jin Ho,Kang Ho Young,Jeong Jin-Yong Korean Society of Life Science 2005 생명과학회지 Vol.15 No.6
메트로니다졸은 인체 위장질환의 원인균인 헬리코박터 파일로리를 박별하기위해 처방하는 주요 약제이다 그러나 인체로부터 분리한 헬리코박터 파일로리 균주는 메트로니다졸에 내성을 가지는 경우가 일반적이며, 이러한 내성원인은 이 균주의 염색체 상에 존재하는 두 종류의 nitroreductase 유전자인 rdxA와frxA 유전자가 비활성화됨에 따라 유발된다. 본 연구에서는 헬리코박터 파일로리 균에서 rdxA 유전자에 변이를 도입하여 메트로니다졸에 내성을 가지는 균주를 구축하여, 메트로니다졸 내성이 균주에 미치는 생물학적 영향을 관찰하고자 하였다. In vitro상에서 메트로니다졸 내성균주는 대조균과 비교하여 exponential phase에서는 거의 차이 없이 증식하였으나 stationary phase에서는 빠르게 생육활성을 잃는 것을 관찰할 수 있었다. 또한 생쥐를 이용한 동물 실험에서 메트로니다졸 내성균주는 생쥐의 위장 내에서 서식하는 능력을 상실함을 알 수 있었다. 그러나 이러한 생육 활성을 회복시켜주는 compensate템 mutation을 가진 균주를 쉽게 얻을 수 있었으며 이 균주는 생쥐에 감염시키면 위장 내에서 서식하는 능력을 회복함을 알 수 있었다. Resistance to metronidazole, a key component of therapies against Helicobacter pylori, is common in clinical isolates. Resistance generally requires inactivation of rdxA (HP0954), and sometimes also frxA (HP0642), two related nitroreductase genes. Here we studied the effect of resistance to metronidazole on fitness of the gastric pathogen H. pylori. The effect of metronidazole resistance for H. pylori in culture was assessed first by looking at colonies formed by freshly constructed mutant derivatives of H. pylori strain 26695. Mutations resulting in metronidazole resistance caused premature death of H.pylori in stationary phase, but had no significant effect on early exponential growth. The effect of nitroreductase deficiencies on fitness in vivo was tested by infecting C57BL/6 mice with 1:1 mixtures of SS1 wild type and its isogenic metronidazole resistant derivatives. Inactivation of rdxA caused an inability to colonize mice in SS1 H. pylori strain. Derivatives of a metronidazole resistant strain that survived better in stationary phase, although remaining metronidazole resistant, could again colonize mice. In conclusion, metronidazole resistance diminishes H. pylori's fitness, but their costs can be suppressed by additional mutation.
한국인 크론병 환자에서 NOD2 유전자 돌연변이의 빈도분석
이진혁 ( Gin Hyug Lee ),김찬규 ( Chan Gyoo Kim ),김주성 ( Joo Sung Kim ),정현채 ( Hyun Chae Jung ),송인성 ( In Sung Song ) 대한소화기학회 2005 대한소화기학회지 Vol.45 No.3
Background/Aims: Several studies from Western populations have recently shown that three mutations in NOD2 gene (C2104T, G2722C, and 3020insC) are associated with susceptibility to Crohn`s disease (CD). However, three mutations were shown not to be associ
십이지장 궤양 발생과 Helicobacter pylori 균주의 cagA, vacA 및 iceA 유전자형과의 상관관계
이경아 ( Kyung A Lee ),명승재 ( Seung Jae Myung ),홍성수 ( Seong Soo Hong ),김진호 ( Jin Ho Kim ),조윤경 ( Yoon Kyung Cho ),정훈용 ( Hwoon Yong Jung ),이진혁 ( Gin Hyug Lee ),이윤정 ( Yun Jung Lee ),변정식 ( Jeong Sik Byeon ),양 대한내과학회 2005 대한내과학회지 Vol.69 No.3
Background: The aims of this study were to evaluate whether genotypes of Helicobacter pylori are different between the gastric antrum and duodenal bulb in order to assess the roles of duodenal H. pylori strains in development of duodenal ulcer. Methods: Forty-eight H. pylori infected patients (duodenal ulcer 28, chronic gastritis 20) were included for the study. Biopsy specimens were taken separately from the antrum and duodenal bulb for the histologic examination and H. pylori culture. cagA, vacA, and iceA genotypes of H. pylori were examined by polymerase chain reaction and H. pylori DNA subtypes by random amplified polymorphic DNA (RAPD) fingerprinting. Results: H. pylori genotypes were not significantly different between antrum and duodenal bulb of the duodenal ulcer and chronic gastritis. RAPD fingerprinting showed different H. pylori strains between the gastric antrum and duodenal bulb in 2 patients with duodenal ulcer. Most prevalent genotype was cagA+ vacA s1/m1 iceA1 in duodenal ulcer (15/16). Conclusion: The host factor or other genotypes may play the major roles in duodenal ulcerogenesis compared with H. pylori genotype itself. (Korean J Med 69:264-273, 2005)
제균 치료에 반응하지 않은 유전자 전좌를 동반한 MALT 위림프종 1예
이욱진 ( Wook Jin Lee ),정훈용 ( Hwoon Yong Jung ),윤덕현 ( Dok Hyun Yoon ),최기돈 ( Kee Don Choi ),송호준 ( Ho June Song ),이진혁 ( Gin Hyug Lee ),김진호 ( Jin Ho Kim ) 대한내과학회 2009 대한내과학회지 Vol.76 No.6
About 90% of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas are strongly related to Helicobacter pylori infection. The eradication of the H. pylori by antibiotics leads to complete regression of the gastric MALT lymphoma in 80% of cases, and this is currently recommended as the first-line treatment for this tumor. However, no standard treatment for H. pylori-negative and H. pylori-eradication-resistant gastric MALT lymphomas has yet been devised. The association between H. pylori-negative MALT lymphoma and the t(11;18)(q21;q21) translocation, resulting in an API2-MALT1 chimera gene, was reported, and is now considered one of the possible causes of and a reliable predictive marker for unresponsiveness to H. pylori-eradication treatment in patients with low-grade gastric MALT lymphoma. We report a case of H. pylori-eradication-treatment-resistant low-grade gastric MALT lymphoma that was treated successfully with radiotherapy after recognizing the API2-MALT1 chimera gene. (Korean J Med 76:737-741, 2009)
장결핵의 진단을 위한 대장내시경 생검과 장외결핵의 유용성
이윤정 ( Yun Jung Lee ),양석균 ( Suk Kyun Yang ),명승재 ( Seung Jae Myung ),변정식 ( Jeong Sik Byeon ),박일권 ( Il Gwon Park ),김정선 ( Jung Sun Kim ),이진혁 ( Gin Hyug Lee ),정훈용 ( Hwoon Yong Jung ),홍원선 ( Weon Seon Hong ) 대한소화기학회 2004 대한소화기학회지 Vol.44 No.3
Background/Aims: Intestinal tuberculosis can be difficult to diagnose because it may mimic many other intestinal diseases. The aim of this study was to evaluate the diagnostic yield of colonoscopic biopsy and frequency of concomittent extra-intestinal tub
23 오심 및 구토의 발생으로 Azathioprine투여를 중단했던 크론병 환자에서 6-Mercaptopurine의 사용
이현주 ( Hyun Ju Lee ),양석균 ( Suk Kyun Yang ),명승재 ( Seung Jae Myung ),이장교 ( Chang Gyo Lee ),김태훈 ( Tae Hun Kim ),이진혁 ( Gin Hyug Lee ),정훈용 ( Hwoon Yong Jung ),홍원선 ( Weon Seon Hong ),김진호 ( Jin Ho Kim ),민영일 ( 대한소화기학회 2002 대한소화기학회 추계학술대회 Vol.2002 No.-
박일권 ( Park Il Gwon ),이윤정 ( Lee Yun Jung ),박도현 ( Park Do Hyun ),한송이 ( Han Song Yi ),이진혁 ( Lee Gin Hyug ),명승재 ( Myung Seung Jae ),양석균 ( Yang Suk Kyun ),홍원선 ( Hong Weon Seon ),김진호 ( Kim Jin Ho ),민영일 ( Mi 대한소화기학회 2003 대한소화기학회지 Vol.42 No.1
Extramedullary plasmacytoma is a rare disease in which a neoplastic proliferation of plasma cells originates from the outside of the bone marrow. The jejunum is the most common site of extramedullary plasmacytoma of the gastrointestinal tract and its common complications are intestinal obstruction due to mass, gastrointestinal bleeding, and intussusception. A 68-year-old woman presented with intermittent postprandial abdominal pain, vomiting, and weight loss. Abdomen and pelvis CT revealed diffuse wall thickening of the proximal jejunum. Small bowel series and enteroclysis revealed a short segment stricture of the proximal jejunum. A 2 cm long jejunal stricture was detected on peritoneoscopic surgery. A pathology showed a solid mass beneath the submucosa grossly and malignant plasma cell infiltration microscopically. A immunochemical staining showed monoclonal kappa chain expression. A bone marrow examination showed only mild reactive plasmacytosis. Serum protein electrophoresis, skull and spine X-ray showed no specific abnormality, and urinary Bence Jones protein was negative. (Korean J Gastroenterol 2003;42:67-71)
소화기; 서울 3차 의료기관에서 분리한 헬리코박터 파일로리 항생제 내성률 변화
최원정 ( Won Jung Choi ),도기원 ( Gi Won Do ),이진혁 ( Gin Hyug Lee ) 대한내과학회 2014 대한내과학회지 Vol.86 No.3
Background/Aims: Patient compliance and resistance to antibiotics are main factors determining the success of Helicobacter pylori eradication. This study provides basic data to verify the efficacy of currently implemented eradication therapy and reports changes in H. pylori resistance to all antibiotics used at Asan Medical Center, Seoul, Korea from 2004 to 2010. Methods: We investigated the resistance rates to amoxicillin, clarithromycin, metronidazole, ciprofloxacin, and levofloxacin in 88, 100, and 47 strains isolated from adult patients without H. pylori eradication history in 2004, 2007, and 2010. Results: The resistance rate to amoxicillin increased from 5.0% in 2007 to 10.6% in 2010. The resistance rate to clarithromycin increased from 10.2% in 2004 and 11.0% in 2007 to 14.8% in 2010. However, no difference was observed in the resistance rate to metronidazole, and strains resistant to tetracycline were not detected at all in this study. The resistance rates to quinolone lingered at 15-17% for 3 years. The non-resistant strains to antibiotics accounted for 56% of the total in 2004 and 62% in 2007. In contrast, a decreasing tendency was found for those strains in 2010 (43%). No significant differences were shown in the multi-drug resistance rate or the co-resistance rates of amoxicillin and clarithromycin over the 3 years. Conclusions: We showed increased resistance rates to clarithromycin and amoxicillin over the last 7 years, aligning with the results of previous studies performed domestically. Efforts are needed to inhibit the increase in resistant bacteria to maintain the effectiveness of eradication therapy.
한국인에서 획득한 Helicobacter pylori의 CagA에 존재하는 SHP-2 binding site의 분석
조지윤,정진용,강호영,김군도,변정식,명승재,정훈용,양석균,홍원선,김진호,이진혁,Jo Ji-Yun,Jeong Jin-Yong,Kang Ho Young,Kim Gun-Do,Byeon Jeong-Sik,Myung Seung-Jae,Jung Hwoon-Yong,Yang Suk-Kyun,Hong Weon-Seon,Kim Jin-Ho,Lee Gin Hyug 한국생명과학회 2005 생명과학회지 Vol.15 No.6
최근에 발표된 연구 결과에 의하면 pylori CagA내에 존재하는 SHP-2 binding site의 아미노산 서열을 분석한 후, 특정 서열이 위선암의 발병과 연관되어 있다고 보고하였다. 그러나 한국인을 대상으로 CagA 내 에 존재하는 SHP-2 binding site아미노산 서열의 특성을 밝힌 연구는 없다. 따라서 본 연구는 한국인에서 획득한 H. pylori의 CagA SHP-2 binding site에 대해 아미노산 서열을 분석하여 그 특성을 알아보고자 하였다. 총 62 균주의 H. pylori 를 분석한 결과 환자의 질환과 관계없이 모든 H. pylori 균주에서 East Asian (A-B상 혹은 A-B-B-D)을 보여주었다. 일본과 더불어 한국은 위선암 유병률이 높은 나라이므로, 연구 대상의 모든 한국인에서 East Asian type CagA를 가진 H. pylori가 발견된 것이 위선암 유병률과 연관될 가능이 높아 보인다. 그러나 H. pylori의 발병 기전을 보다 더 명확히 이해하기 위해서는 보다 많은 국가와 지역을 대상으로 이러한 유전형 조사가 필요할 것 같다. Recently the pathological actions of CagA of Helicobacter pylori (H. pylori) on gastric epithelial cells have been reported. CagA is directly injected into the host cytoplasm and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes according to the amino acid sequence in the 3'region of CagA; i) the East Asian type (A-B-D of EPIYA motifs) and ii) the Western type (A-B-C of EPIYA motifs). Repeated EPIYA motifs in the 3'region of CagA are involved in the interaction with SHP-2. The East Asian type conferred stronger SHP-2 binding activity than the Westrrn type of CagA. Here we analyzed the amino acid sequences of the SHP-2 binding site of cagA gene in H. pyzori, and investigated whether there is my relationship between the diversities of cagA and the disease out-come in Korea. Most of Korean H. pylori strains showed A-B-D motifs(the East Asian type), and only one strain showed A-B-B-D motifs. In Korea, the incidence of atrophic gastritis and gastric cancer is significantly high compared with Western countries. The high frequency of the East Asian type CagA among Korean H. pylori strains would be involved in increasing the risk of gastric cancer in Korean populations.
변정식 ( Jeong Sik Byeon ),양석균 ( Suk Kyun Yang ),이윤정 ( Yun Jung Lee ),최재원 ( Jae Won Choe ),이진혁 ( Gin Hyug Lee ),명승재 ( Seung Jae Myung ),정훈용 ( Hwoon Yong Jung ),홍원선 ( Weon Seon Hong ),김진호 ( Jin Ho Kim ),민 대한장연구학회 2003 Intestinal Research Vol.1 No.1
The pathogenesis of ulcerative colitis is complicated and both the genetic and environmental factors contribute to its development. Familial occurrence is an example indicating that both the genetic and environmental factors play some parts in the development of ulcerative colitis because family members have similar genetic characteristics and have been exposed to similar environment. Familial ulcerative colitis is observed in about 10% to 20% of patients. Most such families contain only 2 affected members and families containing more than 2 affected members are relatively rare. We experienced a case of familial ulcerative colitis in which all 4 members (both spouses and their 2 sons) were affected. They had lived together for 29 years before all 4 members were affected. The first patient was diagnosed after 14 years of cohabitation and the rest were affected 13, 14, and 15 years after the first diagnosis. We report this case with a review of literature. (Intestinal Research 2003;1:72-77)