• 생명과학회지
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• 제15권6호
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• pp.904-908
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• 2005

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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.9027-9031
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• 2014

Background: Helicobacter pylori (H. pylori) infection is an established cause of peptic ulcers and gastric cancer. The aim of this study was to identify H. pylori genotypes and to examine their associations with geographical regions and gastritis, peptic ulcers and gastric cancer in Laos. Materials and Methods: A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010 - March 2012 were enrolled. Two biopsy specimens (one each from the antrum and corpus) were obtained for CLO testing and only CLO test-positive gastric tissue were used to extract DNA. PCR and sequencing were identified for variants of the cagA and vacA genotypes. Results: Some 119 Laos patients (36.2%) were found to be infected with H. pylori including 83 with gastritis, 13 with gastric ulcers (GU), 20 with duodenal ulcers (DU) and 3 with gastric cancer. cagA was detected in 99.2%. East-Asian-type cagA (62%) and vacA s1c (64.7%) were predominant genotypes in Laos. vacA s1c-m1b was significantly higher in GU than gastritis (53.8% vs. 24.1%; P-value=0.04) whereas vacA s1a-m2 was significantly higher in DU than gastritis (40.0% vs. 16.9%; P-value=0.03). East-Asian-type cagA and vacA s1c were significantly higher in highland than lowland Lao (100% vs. 55.8%; P-value=0.001 and 88.2% vs. 61.5%, P-value=0.03 respectively). Conclusions: H. pylori is a common infection in Laos, as in other countries in Southeast Asia. The cagA gene was demonstrated in nearly all Laos patients, cagA and vacA genotypes being possible important factors in explaining H. pylori infection and disease outcomes in Laos.

• 대한미생물학회지
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• 제35권1호
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• pp.19-29
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• 2000

Although most persons infected with Helicobacter pylori harbor a single strain of the organism, multiple strain colonization in the same patient is also occasionally reported in developed countries. The aims of this study were to determine the prevalence of multiple strain colonization in Korean patients and to detect the cagA, iceA1, and babA status of H. pylori isolated from the antrum and body of the stomach. H. pylori was obtained from 35 patients from the antrum and body of the stomach. The genomic diversity of H. pylori was determined by random amplified polymorphic DNA analysis. The status of cagA, iceA1, and babA genes of H. pylori was assessed by polymerase chain reaction with appropriate primers. Clearly different diversity patterns were identified among the isolates from 35 individual patients. Eighteen (51.4%) patients had a single strain of H. pylori. Eight (22.9%) and nine (25.7%) patients had subtypically (one or two bands difference) and typically (clearly different pattern) different strains of H. pylori in the antrum and body, respectively. Among the 70 isolates of H. pylori from 35 patients, the positive rates of 349-bp and 208-bp cagA gene fragments and the iceA1 gene were 68/70 (97.1%), 68/70 (97.1%), and 58/70 (82.9%), respectively. However, the babA gene was found in 22/66 cases (31.4%). In five out of 18 patients with a single strain, the genetic status of cagA, iceA1, and babA varied between the isolates from the antrum and the body. In 8/17 patients with sub typically or typically different strains, the gene status differed between antrum and body isolates. The prevalence of co-colonization with typically or subtypically different strains is high in Korea, and sub-clones with different pathogenic gene status exist within strains of identical RAPD patterns.

• 농업과학연구
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• 제48권2호
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• pp.353-365
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• 2021

Previously, we reported that tissue factor (Tf) was included in the list of differentially expressed genes as an upregulated gene in a rejected porcine heart after xenotransplantation into monkey. In this study, we analyzed that expression of Tf in aortic endothelial cells (pAEC) isolated from alpha 1,3-galactosyltransferase knockout pig in response to allogeneic porcine serum and xenogeneic human serum. The consequence was significant upregulation of Tf expression by responding to human serum compared with porcine serum. To analyze the function of Tf gene as a promoter, we constructed reporter vectors for expression of luciferase linked to 1,246 and 787 base pairs of porcine Tf (pTF1246 and pTF787), and 535 base pairs of human TF (hTF535) sequences including putative promoter regions and AP-1 biding site at the 5' end. The reporter vectors were transfected into pAEC including cytomegalovirus enhancer/chicken β-actin (CAG)-luciferase vector as a control. Luciferase assay showed that all of the promoters were insufficient to express luciferase compared with CAG promoter in basic culture conditions. Notably, pTF1246, pTF787, and hTF535 led to a significant increase of luciferase expression in response to human serum compared with porcine serum while no change of CAG. pTF1246 and pTF787 showed higher expression than hTF535. Taken together, our findings suggest that pTF1246 and pTF787 promoters could mediate target gene expression specifically at xenogeneic stress condition.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제7권2호
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• pp.137-142
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• 2004

목적: 우리 나라 소아에 감염된 H. pylori에서 PCR RFLP를 이용하여 clarithromycin 내성의 원인으로 알려진 23S rRNA의 돌연변이를 찾아내고, cagA, vacA 유전형과 clarithromycin 내성 돌연변이 사이에 연관이 있는지 알아보고자 하였다. 방법: 서울대학교병원 소아과에서 위내시경검사를 통해 H. pylori 위염으로 진단 받은 환아 27명의 내시경 생검 조직에서 H. pylori cagA, vacA 유전자를 증폭하여 유전형을 조사하였다. H. pylori의 23 rRNA V domain을 조사하기 위해 증폭한 후, PCR 산물은 BsaI과 MboII 제한효소로 처리하여 PCR RFLP를 이용하여 돌연변이 여부를 판정하였다. 결과: A2143G 돌연변이가 1명에서, A2144G 돌연변이가 4명에서 발견되어 18.5%가 clarithromycin 내성으로 관찰되었다. cagA 양성이 25명(93%)이었고, vacA s1a/m1이 6명(22%), s1a/m2가 3명(11%), s1c/m1이 16명(59%), s1c/m2가 1명(4%)이었다. clarithromycin 내성 돌연변이를 보이는 경우는 모두 cagA 양성이었고 s1a/m1이 2명, s1c/m1이 2명으로 특정 유전형이 clarithromycin 내성 돌연변이와 연관성을 보이지 않았다. 결론: 위점막 조직에서 PCR-RFLP를 이용한 H. pylori의 clarithromycin 내성 검사는 항생제를 선택하는데 유용하다고 생각된다. Clarithromycin 내성 돌연변이는 cagA, vacA 유전형과 연관성이 없었다.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.118-123
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• 2006

Dentatorubropallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder usually inherited in an autosomal dominant pattern. DRPLA has been shown to be associated with expansion of an unstable cytosine-adenine-guanine (CAG) trinucleotide repeat in a gene on chromosome 12p. We evaluated a family with DRPLA that affected three members; A 35-year-old female presented with seven year history of gait ataxia, dysarthria and mild cognitive impairment. The MRI of the brain revealed diffuse cerebellar atrophy with an incidental lipoma in the midbrain. Her 30-year-old brother presented with progressive cerebellar ataxia that developed at the age of 20. Her grandmother and mother were reported to have developed ataxia during the late period of their life, and died at the age of 60 and 55, respectively. The demonstration of an expanded CAG repeat in the gene for DRPLA was used to confirm the diagnosis.

• Natural Product Sciences
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• 제23권3호
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• pp.175-182
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• 2017

This study evaluated the anti-Helicobacter and anti-inflammatory effects of Sohamhyungtang (SHHT). The minimum inhibitory concentration (MIC) of SHHT against Helicobacter pylori (H. pylori) was determined by the agar dilution method. Expression of the H. pylori cagA gene in the presence of SHHT was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Inhibition of H. pylori urease by SHHT was determined by the phenol-hypochlorite assay. Antiadhesion activity of SHHT was measured by urea-phenol red reagent. Inhibition of nitric oxide (NO) production in AGS cells was measured with Griess reagent. Inducible nitric oxide synthase (iNOS) and IL-8 mRNA expression in AGS cells which were infected with H. pylori was determined by qRT-PCR. IL-8 level was measured by enzyme-linked immunosorbent assay (ELISA). The MIC of SHHT was $100{\mu}g/mL$ and the expression of cagA gene was decreased about 25 folds in the presence of SHHT. H. pylori urease was inhibited 90% by SHHT. SHHT inhibited H. pylori adhesion on AGS cell in a concentration dependent manner. mRNA expression of iNOS and IL-8 and the production of NO and IL-8 were significantly decreased in the presence of SHHT. In conclusion, SHHT showed anti-Helicobacter activity and has potent anti-inflammatory effect on H. pylori-induced inflammation in human gastric epithelial AGS cells.

• 미생물학회지
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• 제48권2호
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• pp.109-115
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• 2012

Helicobacter pylori는 만성 위염, 소화성 궤양, 위암의 중요한 역학적 인자중 하나이다. H. pylori의 독성인자중 CagL은 숙주 세포와 H. pylori의 제 4형 분비기관(Type 4 secretion system)을 연결하는 adhesin으로 작용하는 섬모 단백질로 H. pylori가 발병하는데 중요한 역할을 하는 것으로 알려져 있다. 이번 연구는 저빌에 H. pylori를 감염시킨 동물 모델을 이용하여 CagL 재조합 단백질을 면역화시켰을 때 나타나는 효과를 평가하였다. 재조합 CagL은 클론되었고, 과발현시켜 정제하여 준비하였다 저빌은 H. pylori 감염 대조군과 H. pylori 감염 CagL 재조합 단백질 접종군으로 분류하였고, 접종시 알루미늄 애쥬번트를 사용하였다. 일주일 간격으로 4회 근육내 접종하였고, 마지막 접종 일주일 후, 모든 저빌에 H. pylori 7.13 균주를 $1{\times}10^9\;bacteria/500{\mu}l$ 농도로 위내 투여하였다. H. pylori 감염 6주째 모든 저빌을 희생하여 혈청 IgG 반응평가를 위한 ELISA를 실시하였고, 위에서는 집락화된 H. pylori의 수평가, 병리조직학적 평가 및 사이토카인 유전자발현을 조사하였다. CagL 재조합 단백질접종 일주일 후부터 H. pylori 감염 CagL 재조합 단백질 접종군의 혈청내 IgG 항체형성이 유의적으로 증가하였다. 위에서의 집락화된 세균수는 두군의 차이가 없었다. 저빌 체중에 대한 위무게 비율는 H. pylori 감염 CagL 재조합 단백질 접종군이 유의적으로 감소하였으나 병리조직학적 평가에서는 유의적인 차이는 확인하지 못하였다. 위에서의 IL-$1{\beta}$와 KC (IL-8 homologues)의 유전자발현 정도도 두 군사이에 유의적인 차이는 없었다. 이번 결과는 CagL 재조합 단백질의 접종은 IgG 항체형성은 효과적으로 자극하였지만 면역화된 숙주에서 세균 집락화의 감소 및 병변형성의 방어까지는 유도하지 못한 것으로 나타났으며, 앞으로 H. pylori 감염에 대해 유효한 면역 반응 및 질병 방어 효과를 나타내기 위해서 CagL을 포함한 다른 종류의 재조합 항원 사용 및 보조적으로 전신 면역 및 점막 면역을 효과적으로 유도하기 위해 안정성있는 애쥬번트의 사용을 고려해야 할 것으로 사료된다.

• Journal of Genetic Medicine
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• 제4권1호
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• pp.84-87
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• 2007

척수소뇌성 실조증3는 신경세포의 손상으로 인해 생기는 질병으로 염색체14q32.1지역에 반복적인 CAG 삼염기 서열이 증가하면서 일어나는 것으로 알려져 있다. 본 증례는 척수소뇌성 실조증3으로 진단을 받은 부부에서 자연 임신한 태아를 산전진단한 경우로서 형광으로 포식된 표지자를 이용하여 CAG 지역을 증폭하여 빠르고 정확하게 반복수를 확인하는 방법을 이용하였다. 남편의 경우 CAG반복을 넘는 69개의 반복과 정상인 27개의 반복된 유전자를 갖고 있는 것으로 확인하였으며, 산모의 경우 정상인 26과 32개의 반복된 유전자를 갖고 있는 것으로 확인하였다. 태아는 부계의 27과 모계의 26개를 갖는 정상 유전자를 물려 받은 것으로 확인되어 건강한 아기를 분만하였다. 형광을 이용한 진단방법은 방사능을 사용하는 방법에 비해 안전하고 빠른 진단을 할 수 있으며 시료 채취 후 5-6시간 안에 정확하게 결과를 확인할 수 있는 방법이라 생각된다.

• Genomics & Informatics
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• 제9권2호
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• pp.64-68
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• 2011

Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR ) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.