Helicobacter pylori cagE 유전자 다형성이 위상피세포주에서 Interleukin-8 유도능에 미치는 영향

이수민,이학성,이인석,조유경,한혜원,오정환,박재명,최명규,정인식,Lee Su-Min,Lee Hak-Sung,Lee In-Suk,Co Yu-Kyung,Han Hae-Won,Oh Jung-Hwan,Park Jae-Myung,Choi Myung-Gyu,Chung In-Sik 한국생명과학회 2004 생명과학회지 Vol.14 No.6

Helicobacter pylori infection is highly prevalent, as high as 2/3 of whole population infected, in Korea. H. pylori infection initiates inflammation by induction of interleukin-8 through type IV secretion of CagA. It was recently suggested that induction failure of IL-8 is not associated with defect in cag PAI but associated with cagE locus diversity. This study was designed to investigate ability of 11-8 in-duction according to sequence variation within the cagE gene, cagA TP motifs and vacA m-types in vitro study using AGS cell-line, and to evaluate its association with different clinical outcome. Seventy-four H. pylori stains were isolated from 23 patients with gastric cancer (Ca), 24 subjects with gastritis (G) and 27 patients with duodenal ulcer (Du) in Kangnam St. Mary's Hospital, Seoul, Korea. cagE gene diversity was confirmed by the PCR-RFLP methods with MboI/NlaIII and tyrosine phosphate motifs (TPMs) of cagA was determined TPM-A and C by using DdeI/Tsp5091 restriction enzyme and TPM-B was determend by Real time PCR the method of Owen et al. and IL-8 was measured by ELISA assay. IL-8 activity was positively detected in 59 among 74 strains $(79.7\%)$. IL-8 secretion was significantly increased in MboI A and MboI B type compared to MboI C type and in MboI/NlaIII A-C and B-C type than C-C type. 1L-8 activity was not associated with either the number or composition of cagA tyrosine phosphorylation motifs and vacA m-type. There was no significant difference in IL-8 activity among patient groups. cagE gene diversity is thought to be mainly associated with the induction of IL-8 in H. pylori infection. 한국에서 분리한 Helicobacter pylori 균주가 위암 세포주에서 IL-8를 유도하는 유도능을 관찰하고자 하였으며, 특히 4형 분비구조의 주요 구성체인 cagE 유전자의 다형성에 따라 IL-8 유도능의 차이 및 각 질환에서 분리한 균주에서의 차이가 있는지 검토하고자 하였다. 강남성모병원 내시경검사를 받은 환자들 중 H. pylori 감염 양성으로 확인된 위암 23명 $(31.0\%)$, 위염 24명$(32.6\%)$, 십이지장궤양27명$(36.4\%)$ 총 74명을 대상으로 하여 H. pylori를 분리한 후 PCR-RFLP방법을 이용하여 cagE 다형성을 확인하였으며, PCR 및 Real-time PCR을 이용하여 ragA TPMs를 결정하였다, 또한 분리된 균주를 위암세포주에 감염시켜 상등액을 취하여 ELISA방법으로 IL-8을 정량화 하였다. 전체 74개의 분리 균주 중 59개의 균주$(79.7\%)$에서 IL-8 유도능이 있는 것으로 확인되었으며, cagE 다형성 중에서 가장 높은 빈도로 관찰되는 형태는 MboI/NlaIII B-C, A-C 및 C-C 타입 이었으며, 이중 A-C와 B-C 형태가 C-C 형태에 비해 유의적으로 높은 IL-8 유도능을 나타냈다. 그러나 cagA TPMs의 분류 및 vacA m-아형 분류와 IL-8 유도능과는 연관성이 없었다. 비록 본 연구에서 cagE 다형성과 IL-8 유도능과 아주 밀접한 연관성이 나타나지는 않았지만 vacA m-아형이나 cagA TPMs 보다는 cagE 다형성이 IL-8 유도능과 연관성이 클 것으로 생각된다.

5'-Untranslated Region에 존재하는 Iron Responsive Element에 의한 Ferritin 합성조절

정인식,이중림,김해영,Chung, In-Sik,Lee, Jung-Lim,Kim, Hae-Yeong 한국응용생명화학회 1998 Applied Biological Chemistry (Appl Biol Chem) Vol.33 No.2

철의 대사과정에 관여하는 ferritin 단백질의 발현은 ferritin transcript의 5'-untranslated region에 위치한 iron-responsive element (IRE)와 철 농도 조절 단백질의 결합에 의해 조절된다. 이러한 ferritin의 생성에 관여하는 구조적인 요소를 밝히기 위해, RNA 이차구조인 IRE의 bulge 부분을 다른 염기로 변환시켜 철 농도 조절단백질에 의한 RNA 결합력과 ferritin 단백질의 생성의 저해정도를 비교 측정하였다. 측정된 결과로부터 IRE의 bulge 부분의 시토신 염기배열만이 RNA 이차구조의 형성에 중요한 작용을 하여 ferritin 합성을 조절할 수 있는 것을 보였다. The expression of ferritin involved in iron metabolism is regulated at the translational level by the interaction of iron regulatory protein with iron-responsive element(IRE) in the 5'-untranslated region of ferritin transcript. To identify the role of structural element utilized for translational regulation of ferritin, we studied the effects of mutations in the ferritin IRE by measuring IRP binding activity and translational activity. Our data suggest that the cytosine at bulged position of IRE within ferritin is important for the formation of RNA secondary structure involved in translational regulation.

한국인에서 Helicobacter pylori 감염의 진단에 있어 Genedia™ H . pylori ELISA 검사의 진단 정확도

정인식(In Sik Chung),김상우(Sang Woo Kim),고재성(Jae Sung Go),김나영(Na Young Kim),김재규(Jae Gyu Kim),김진호(Jin Ho Kim),김학양(Hak Yang Kim),김재준(Jae Jun Kim),노임환(Im Hwan Roe),심재건(Jae Geon Sim),안형식(Hyeong Sik Ahn),윤병철(By 대한내과학회 2001 대한내과학회지 Vol.61 No.1

N/A Background: Genedia™ H. pylori ELISA is a newly developed diagnostic method which detects serum anti-H. pylori IgG antibody. The aim of this study was to assess the accuracy of Genedia™ H. pylori ELISA for the diagnosis of H. pylori infection in Korean population. Methods Genedia : H. pylori ELISA and GAP-IgG were performed in 353 adult sera and Pyloriset-IgG EIA in 184 subjects. In children, 43 serum samples were tested with Genedia™ H. pylori ELISA. H, pylori infection was determined by rapid urease test, histology, culture or (13)C-urea breath test in adults. In children, the subject was considered to he H. pylori positive if (13)C-urea breath test was positive. Results: In adults, the sensitivity and specificity of Genedia™ H. pylori ELISA were 93.2% and 83.5% with positive and negative predictive values of 85.1% and 92.5%. Those for GAP-IgG and Pyloriset-IgG EIA were 67.2%, 82.4%, 79.3%, 71.4% and 89.1%, 88.4%, 71.9%, 96.1%, respectively. In children, sensitivity, specificity, positive and negative predictive values of Genedia™ H. pylori ELISA were 80%, 84.8%, 61.5%, and 93.3%. Sensitivity and negative predictive value of Genedia™ H. pylori ELISA were significantly higher than those of GAP-IgG (93.2% vs. 67.2%, p<0.005 and 92.5% vs 71.4%, p<0.005, respectively). Conclusion : Genedia™ H pylori ELISA is a relatively accurate method for the serodiagnosis of H pylori infection in Korean subjects compared to GAP-IgG. These results may suggest the clinical use of Genedia™ H. pylori ELISA for epidemiological studies of H. pylori infection in Korea. (Korean J Med 61:17-23, 2001)

Helicobacter pylori 제균요법 적용의 실태 분석: 단일 기관 연구

정우철 ( Woo Chul Chung ),이강문 ( Kang Moon Lee ),백창렬 ( Chang Nyol Paik ),이정록 ( Jeong Rok Lee ),정성훈 ( Sung Hoon Jung ),김진동 ( Jin Dong Kim ),한석원 ( Sok Won Han ),정인식 ( In Sik Chung ) 대한소화기학회 2009 대한소화기학회지 Vol.53 No.4

목적: 현재 H. pylori 제균치료는 소화성 궤양 환자에서만 인정을 받고, 위암이나 위염 환자를 대상으로 적용 범위를 확대 적용하는 것에는 아직 논란의 여지가 있다. 최근 들어 표준 삼제요법의 제균율이 점차 감소하는 경향을 보이며, 이는 항생제 내성의 증가 및 환자의 순응도 감소와 가장 큰 연관이 있으나, 다른 여러 요인들도 제균율에 영향을 미치는 것으로 알려져 있다. 저자들은 진료과에 따른 제균율의 차이가 있는지 알아보기 위해 진료과별 제균치료 현황과 제균율, 그리고 내시경적인 궤양에 대한 적용 빈도를 조사하였다. 대상 및 방법: 2003년 1월부터 2007년 6월까지 가톨릭대학교 성빈센트병원에서 H. pylori 제균요법을 시행했던 환자를 대상으로 소화기내과, 일반내과, 가정의학과별로 제균율의 차이를 후향 조사하였다. 대상 환자는 2,050명으로 의료영상 저장 전송 체계(PACS)를 이용하여 3명의 내시경전문의가 각각의 내시경 소견을 다시 판독하여 내시경적인 미란과 궤양을 구분하였다. 결과: 일차 삼제요법에 대한 제균율은 82.5%였고, 이차 사제요법에 대한 제균율은 71.2%였다. 일차 진료를 담당하는 가정의학과와 내과 일반에서 소화기내과에 비해 내시경적인 미란에 대해 제균요법을 시행하는 빈도가 의미 있게 높았고, 전체 제균율과 내시경적인 궤양에 대한 제균율은 유의하게 낮았다. 결론: 일차 진료과에서 적용한 H. pylori 제균요법은 미란 등 부적절한 제균대상이 많았다. 전체적인 제균율이나 내시경적인 궤양에 대한 제균율은 소화기내과가 일차 진료과에 비해 의미 있게 높았고, 이것은 여러 가지 복합적인 요인이 작용하고 있을 것이며, 그 중에서도 복약에 대한 환자의 순응도가 중요한 역할을 할 것으로 본다. Background/Aims: Eradication rates of Helicobacter pylori (H. pylori) tend to decrease over the last few years. Apart from the antibiotic resistance and patient`s compliance, various factors have an influence on the efficacy of eradication therapy. We analyzed the inter-departmental differences in the eradication therapy for H. pylori infection. Methods: Between January 2003 and June 2007, total 3,072 eradication regimens were prescribed to patients. Eradication rates according to departments-gastroenterology (GE), general internal medicine (IM) and family medicine (FM)-were analyzed retrospectively. Results: The overall eradication rate of first-line triple therapy was 82.5% and second-line quadruple therapy was 71.2%. In the department of IM and FM, the eradication therapy was applied more frequently to the patients with erosion only, not ulcer. Overall eradication rates according to the departments were 87.0% in GE, 81.1% in IM and 77.2% in FM (p=0.02 GE vs. IM and p<0.01 GE vs. FM, respectively). Eradication rate in patients with peptic ulcer was also significantly higher in GE compared with IM or FM. Conclusions: In primary clinic (IM and FM), the eradication therapy was frequently applied to erosion. The eradication rates of H. pylori in GE department were significantly higher than those of IM or FM. Inter-departmental differences of the eradication rate might be caused by patients` compliance to prescribed medication. (Korean J Gastroenterol 2009;53:221-227)

위 악성종양 900예의 임상 분석

선희식(Hee Sik Sun),정인식(In Sik Chung),이재학(Jai Hak Lee),주상용(Sang Yong Choo),이종서(Jong Seo Lee),장석균(Suk Kyun Chang),최상근(Sang Geun Choe),안창준(Chang Jun Ahn) 대한소화기학회 1993 대한소화기학회지 Vol.25 No.6

N/A Stomach cancer is the most common malignant tumor in Korea. This study includes 900 stomach cancer cases which were collected at the Departrnent of Surgery, St. Marys Hospital, Catholic University medical College over the period from 1980 to 1991. The patients are divided into two groups: Those treated during the period between 1980 and 1986 - first group and the period between 1987 and 1991 - second group. We followed each patient and then analysed each patient's record using guidelines from the Stomach Cancer Study Group of Korean Surgical Society. There were 889 adenocarcinomas (98.8%), 5 malignant lymphomas (0.5%), 5 leiomyosarcomas (0.5%) and 1 leiomyoblastoma (0.1%). There were 378 patients in the first group and 522 in the second group. The number of second group patients was 1.4 times as many as compared to the first group. Peak age incidence was 6th decade (32%) and male to fema]e ratio was 1.8:1. The difference about age and sex between groups was insignificant. The number of patient under 35 years old was 87 cases (9.7%), Tumor locations were antrum (62.8%), body (27.4%), cardia (5.3%) and whole stomach (3.7%). The tumor location of the second group is more proximal portion of stomach than first group. Operation procedures performed were subtotal gastrectomy (69.1%), total gastrectomy (18.7%), bypass gastrojejunostomy (4.6%), exploratory surgery (6.3%) and proximal gastrectomy (0.8%) and so gastric resection rate was 88.6%. Total gastrectomy of the second group has increased compared to first group, while exploratory surgery has decreased. Regional lymph node metastasis was seen in 60.8% of all cases. Rate of regional lymph node metastasis according to tumor depth were as follows; 16% in T1, 48.4% in T2, 77.3% in T3 and 92.5% in T4, There were 162 cases of early gastric cancer (EGC 18%): 14% in the first group, 20% in the second group. The rate of EGC has significantly increased every year (p<0.05). Overall 5-year-cummulative survival rate was 55.8%. Overall 5-year-cummulative survival rates according to stage were as follows: 98.6% in stage I a, 89.6% in I b, 67% in II, 58.4% in llIa. 29.4% lIlb and 14% in stage IV. overall 5-year-cummulative survival rates according to depth were as follow: 93.9% in Tl, 85% in T2, 48.8% in T3 and 12.4% in T4. Hospital death rate was 1.5%.

쯔쯔가무시병 환자에서의 장내 단백 상실

민준기(Jun Ki Min),정우철(Woo Chul Jung),백기현(Gi Hyun Baek),김양리(Yang Ree Kim),오수혁(Soo Hyuk Oh),강문원(Moon Won kang),정인식(In Sik Chung),양우진(Woo Jin Yang),김성훈(Sung Hun Kim) 대한내과학회 1996 대한내과학회지 Vol.51 No.4

N/A Objectives: Tsutsugamushi disease is an acute, febrile illness of humans that is caused by Rickettsia tsutsugamushi. Hypoalbuminemia was reported in some cases of tsutsugamushi disease, but its frequcncy and etiology were not clarified. Therefore we prospectively evaluated fourteen cases of Tsutsugamushi disease patients to idendify intestinal protein loss as a cause of hypoalbuminemia and to assess the value of 99mTc-HSA abdominal scintigraphy for detecting intestinal protein loss. Methods: From November 1994 to December 1994, in fourteen patients with tsutsugamushi disease, serum albumin level and fecal a-1-antitrysin excretion were measured at admission. Anterior abdominal images were obtained at 2, 4, and 24hours after intravenous injection of 30 mCi of Tc-Human serum albumin. Results: 1) The age distribution was mainly in the forties, and fifties. Geographically, 10 cases in the northern part of Kyung-Ki Do and 4 cases in Seoul were occurred. 2) Laboratory findings showed hypoalbuminemia in 5 cases(35.7%), elevated AST and ALT in 11 cases (78.6%), prolonged prothrombin time in 1 cases (7.1%), and proteinuria(30mg/dl) in 9 cases(64.3%). 3) Fecal a-1-antitrypsin concentration was measured in 10 cases of 14 patients with tsutsugamushi disease, of which 8 cases revealed abnormally elevated concentration of fecal a-l-antitrypsin(2.6mg/g dry weight). 4) 99mTc-HSA scintigraphy was positive in 11 of 1478.696) patients with tsutsugamushi disease. 5) In patients with positive 99mTc-HSA scintigraphy, protein loss sites were small bowel(6/11, 54.5%), descending colon(3/14, 27.3%), ascending colon(2/11, 18.1%). Conclusion: Intestinal protein loss was idendified in some patients with tsutsugamushi disease by the measurement of fecal a-1-antitrpysin concentration. 99mTc-HSA scintigraphy is easy and readily available study for detecting intestinal protein loss sites. The comparison of the severity of intestinal protein loss before and after treatment is recommended in patients with tsutsugarnushi disease who have abnormal intestinal protein loss.

대량의 위궤양 출혈을 일으킨 정상 신생아

박영실 ( Young Sil Park ),정우철 ( Woo Chul Chung ),이강문 ( Kang Moon Lee ),이보인 ( Bo In Lee ),천지성 ( Ji Sung Chun ),장우임 ( U Im Chang ),양진모 ( Jin Mo Yang ),최규용 ( Kyu Yong Choi ),정인식 ( In Sik Chung ) 대한소화기학회 2006 대한소화기학회지 Vol.48 No.3

Gastric ulcer bleeding in neonatal period, mainly in preterm newborn babies or in neonates treated in intensive care units, is relatively frequent, However the occurrence of significant gastric ulcer bleeding in healthy full term infants is unusual. We experienced a case of massive upper gastrointestinal (GI) bleeding in a 3-day-old healthy full term infant. Endoscopic examination confirmed the presence of gastric ulcerations. Treatment was initiated with transfusion and histamine 2 receptor antagonist, and the clinical signs resolved. Mother`s serum antibody to Helicobacter pylori (H. pylori) was positive. We collected stool of the patient including other 17 infants in the intensive care unit. A highly sensitive semi-nested PCR for H. pylori DNA was performed, but all infants including the patient revealed negative. H. pylori infection is not related with upper GI bleeding in healthy full term infants. In conclusion, the diagnosis of upper GI bleeding in infant can be easily made by means of pediatric endoscopy, which is a simple and a well tolerated examination. (Korean J Gastroenterol 2006;48:210-214)

울혈성 간 손상의 임상상과 조직학적 소견

정규원(Kyu Won Chung),정환국(Whan Kook Chung),선희식(Hee Sik Sun),김부성(Boo Sung Kim),정인식(In Sik Chung),안병민(Byung Min Ahn),김재광(Jae Kwang Kim) 대한소화기학회 1989 대한소화기학회지 Vol.21 No.4

N/A To assess the clinical, biochemical and morphological findings in regard to the severity and duration of hepatic venous outflow block we reviewed 22 patients including 6 patients with acute and chronic heart failure (Group I ), 5 patients with constrictive pericarditis (Group II), and 12 patients with Budd-Chiari syndrome (Group lII). Suggestive causes of heart failures were Graves disease, right atrial myxoma, bacterial endocarditis, acute and chronic renal fai]ures and atrial fibrillation. Most of the constrictive pericarditis seenied to be developed by tuberculosis and all of the Budd-Chinri syndrome were suggested to be induced by segrnental obstruction of inferior vena cava at the level of diaphragm with regard to clinical, laboratory, and radiologica] findings. The clinical findings in most of the cases of group I resembled acute viral hepatitis and the cases of latter two groups revealed chronic liver disease. The serum AST,'ALT (:>15+640 unit/321+371 unit) and TB (3. 3+ 3. 6 mg/dl) of group 1 were elevated significantly compared to those (38+ 23 unit,' 20+10, unit, 1.6+1.1 mgi'dl) of group III (p< 0.0;>). The liver cirrhosis with regenerative nodules v, as more cornmonly seen in the cases with Budd- Chiari syndrome (90.99.) than in patients with constrictive pericarditis (20r,), while no hepatic cirrhosis was observed in cases with congestive heart failure. In hepatic congestion, great variations of histological changes throughout the liver partly explain the poor correlation between the structural changes and clinical and Jaboratory findings on the one hand, and between the degree and duration of the cardiac failure and the regi<>n of the venous out-block on the other.

간장 및 담도 : 삼출성 복수증의 감별진단과 복강경 검사

정규원(Kyu Won Chung),차상복(Sang Bok Cha),선희식(Hee Sik Sun),김부성(Boo Sung Kim),정인식(In Sik Chung),안병민(Byung Min Ahn),김재광(Jae Kwang Kim),김태룡(Tae Ryong Kim),최규용(Gyu Yong Choi) 대한소화기학회 1990 대한소화기학회지 Vol.22 No.1

N/A Exudative ascites should initiate an evaluation for peritoneal processes, most importantly infection and tumor. And the pathological diagnosis is required for a approapriate treatment in most cases. To assess the diagnostic accuracy and complication rates of diagnostic laparoscopy in patients with exudative ascites we studied in 73 patients with exudative ascites retrospectively. Thirty three patients had malgnancy related ascites, and peritoneal carcinomatosis was confirmed in thirty one patients. Twenty seven patients had tuberculous peritonitis, and thirteen patients had miscellaneous causes, among them eight patients had underlying liver cirrhosis and clinically spontaneous bacterial peritonitis were suspected in three patients in whom bacteria were cultivated in ascites. Pancreatic pseudocyst and leakage into peritoneal cavity was confirmed by endoscopic retrograde pancreatography in one case, but the remained four cases had not known the diagnosis. The most common primary cancer was gastric carcinoma which was diagnosed in fourteen patients, and then ovarian cancer in five patients, colon cancer in four patients, pancreatic cancer in three patients, mesothelioma in one patient and unknown origin in four patients. Cytology evaluation of the ascitic fluid was positive for tumor cells in 62% of patients with peritoneal carcinomatosis. Blind Cope needle biopsy yielded positive diagnosis of neoplastic or tuberculous in 65.4 per cent of rases. The major and minor complication rates of laparoscopy were 0% and 26.4%, respectively, with no fatalities. These findings compare favorably with general experience. We conclude that laparascopy is relatively safe and accurate diagnostic method of choice in exudative ascites, especially in cases when other non-invasive methods were failed.

HBe 항원 양성 만성활동성간염에서 베타 인터페론의 효과

정규원(Kyu Won Chung),정환국(Whan Kook Chung),선희식(Hee Sik Sun),김부성(Boo Sung Kim),정인식(In Sik Chung),안병민(Byung Min Ahn),김재광(Jae Kwang Kim) 대한소화기학회 1989 대한소화기학회지 Vol.21 No.4

N/A The lack of an effective drug against chronic type B virus infection has led to trials of variety of antiviral drugs. Among these drugs interferon has shown more encouraging results. In all studies, greater HBeAg to anti-HBe seroconversion rates occurred in treated patients than in control. The reason for the use of interferon in this disease is the effectiveness as an antiviral activity. More recently its activity has heen extended as an immunomodulating drug in the immune response. The purpose of this study was to elucidate the effect of human fibroblast interferon (β-interferon) in Korean HBsAg positive chronic active hepatitis. We has conducted therapeutic trial with total l02 X1000000 IU of beta-interferon for 28 days in fifteen cases with needle aspiration biopsy proven chronic activc heaptitis. 1) Six patients (40.0%) lost HBeAg in the serum and four of these patients (26.7%) were seroconverted to anti-HBe after β-interferon therapy. And two patients expressed anti-HBe without loss of HBeAg. However, none of the patients lost HBsAg during the study peroid. 2) The serun ALT began to increased significantly (p<0.05) from the 7th day of interferon therapy and reached its maxinauin level on 10th day of therapy, and then continued to decrease to the level below the pretreatment level in 2nd week after treatment of interferon. 3) Pre-tretament ALT showed higher levels in group of changed viral rnarkers (n=6) than in unchanged (n=8), but there was no statistical significance. 4) Peripheral blood leukocytes and granulocytes showed significant reduction in number from the 3rd day of interferon treatment (p<0.05), and recovered within one week after withdrawal, 5) There was no significant changes in serum protein, bilirubin and prothrombin time. 6) All the treated patients experienced an initial flu-like illness consisting of fever, chills, malaise, myalgia, anorexia, headache and dizzeness. Tachyphylaxis developed gradually during the treatment. The above results suggest that β-interferon therapy may be effective and safe in the treatment of patients ivith tvpe B chronic activc hepatitis.