유전체 전장 연관성 분석에 의한 베체트 장염의 감수성 유전자 발굴

의과대학/박사Several recent genome-wide association studies (GWAS) have identified susceptibility loci/genes for Behcet’s disease (BD). However, no studies have specifically investigated the genetic susceptibility loci associated with intestinal involvement in BD. We evaluated distinctive genetic susceptibility loci/genes associated with intestinal involvement in BD, which can be used to define intestinal BD. GWAS was performed for 100 Korean BD patients without intestinal involvement, 99 with intestinal involvement, and 557 unaffected individuals. Candidate genes derived from GWAS were then validated using independent cohort samples from 138 patients without intestinal involvement and 196 patients with intestinal involvement. Immunohistochemistry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blot, and gene silencing were performed to evaluate functional gene expression in intestinal epithelial cells and in human and murine colon tissues. GWAS and validation studies showed intestinal BD-specific association with the NAALADL2 gene (rs3914501, OR = 1.914, P = 3.5 × 10-4) and YIPF7 gene locus (rs6838327, OR = 1.567, P = 3.4 × 10-4). Haplotype analysis was suggestive of associations between DCAF12, IL10, NAALADL2, PLCB1, SCHIP1, and TGFBR3 with intestinal BD and its disease phenotype. The results suggest that these genes are potentially causal variants in association with intestinal BD. Gene functional and pathway analyses indicated that intestinal BD shares inflammatory pathways with inflammatory bowel disease (IBD). NAALADL2 and YIPF7 displayed exacerbated inflammatory responses in vitro and in vivo. In conclusion, our GWAS results separating between intestinal BD and BD without intestinal involvement enable a more comprehensive analysis of disease specificity and provide insight into the common and different pathogenic mechanisms for intestinal BD and IBDope

A case of adult-onset Still’s disease combined with Sjögren’s syndrome

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Clinical outcomes and predictive factors in oral corticosteroid-refractory active ulcerative colitis

AIM: To evaluate the clinical outcomes and prognostic factors after intravenous corticosteroids following oral corticosteroid failure in active ulcerative colitis patients. METHODS: Consecutive patients with moderate to severe ulcerative colitis who had been treated with a course of intravenous corticosteroids after oral corticosteroid therapy failure between January 1996 and July 2010 were recruited at Severance Hospital, Seoul, South Korea. The disease activity was measured by the Mayo score, which consists of stool frequency, rectal bleeding, mucosal appearance at flexible sigmoidoscopy, and Physician Global Assessment. We retrospectively evaluated clinical outcomes at two weeks, one month, three months, and one year after the initiation of intravenous corticosteroid therapy. Two weeks outcomes were classified as responders or non-responders. One month, three month and one year outcomes were classified into prolonged response, steroid dependency, and refractoriness. RESULTS: Our study included a total of 67 eligible patients. At two weeks, 56 (83.6%) patients responded to intravenous corticosteroids. At one month, complete remission was documented in 18 (32.1%) patients and partial remission in 26 (46.4%). Eleven patients (19.7%) were refractory to the treatment. At three months and one year, we found 37 (67.3%) and 25 (46.3%) patients in prolonged response, ten (18.2%) and 23 (42.6%) patients in corticosteroid dependency, 8 (14.5%) and 6 (11.1%) patients with no response, respectively. Total 9 patients were underwent elective proctocolectomy within 1 year. The duration of oral corticosteroid therapy (> 14 d vs ≤ 14 d, P = 0.049) and lower hemoglobin level (≤ 11.0 mg/dL vs >11.0 mg/dL, P = 0.02) were found to be poor prognostic factors for response at two weeks. For one year outcome, univariate analysis revealed that only a partial Mayo score (≥ 6 vs <6, P = 0.057) was found to be associated with a poor response. CONCLUSION: The duration of oral corticosteroid therapy and lower hemoglobin level were strongly associated with poor outcome.ope

Transthoracic Echocardiographic Detection, Differential Diagnosis, and Follow-Up of Esophageal Hematoma

Esophageal hematoma is a rare form of esophageal injury. It may occur spontaneously, or in association with direct esophageal damage or a bleeding diathesis. Endoscopy and computed tomography are generally necessary for the establishment of a diagnosis. In this report, we present a case of esophageal hematoma that was discovered via a bedside transthoracic echocardiography. The echocardiography was conducted to evaluate an unexplained shock in a critically ill-patient. After conservative treatment, complete resolution of the esophageal hematoma was documented by a 7-day short-term follow-up of bedside transthoracic echocardiography. To the best of our knowledge, this is the first case report regarding transthoracic echocardiographic detection, differential diagnosis, and follow-up for esophageal hematoma.ope

The Early Diagnostic Accuracy for Gastrointestinal T-cell Lymphoma from a Perspective of Gastroenterologists

Background/Aims: Primary T-cell lymphoma of the gastrointestinal tract is a very difficult disease entity to diagnose, and has an extremely poor prognosis. The aim of this study was to determine the early diagnostic accuracy for gastrointestinal T-cell lymphoma by gastroenterologists. Methods: Between January 2000 and October 2010, the clinical features of 15 patients with primary gastrointestinal T-cell lymphomas, including endoscopic findings, radiologic diagnosis, endoscopic biopsy findings, and final diagnosis, were retrospectively reviewed. Results: The most common initial presenting symptoms of primary gastrointestinal T-cell lymphomas was abdominal pain (n=11, 73%). The anatomic location of the primary lesion the small bowel (n=8, 53%), colon (n=5, 33%), and stomach (n=3, 20%). There were no cases of T-cell lymphomas diagnosed based on clinical symptoms, radiologic findings, or endoscopic findings without biopsy alone. Pathologic confirmation of T-cell lymphomas by endoscopic examination was achieved in 7 cases (64%) and the remaining cases (n=8, 53%) were diagnosed with T-cell lymphomas based on pathologic examination after surgery. Conclusions: All of the patients with primary T-cell lymphomas of the gastrointestinal tract were diagnosed exclusively by endoscopic or surgical pathologic examainations, suggesting that gastroenterologists should scrutinize and suspect this disease with caution due to atypical gastrointestinal ulcersope

The Clinical Utility of Positron Emission Tomography-computed Tomography in the Evaluation of Inflammatory Bowel Diseases

Background/Aims: Positron emission tomography-computed tomography (PET-CT) is a nuclear imaging technique that provides noninvasive, three dimensional, quantitative images. Recently, PET-CT has been shown to be valuable in assessing patients with inflammatory diseases; however, the clinical utility of PET-CT in the evaluation of inflammatory bowel disease (IBD) has not been defined. Thus, the aim of this study was to determine the clinical utility of PET-CT in the evaluation of IBD. Methods: Between November 2006 and September 2010, clinical, endoscopic, and radiological data on 14 patients (6 males and 8 females: age range, 33-79 years) with suspected IBD were collected. The standard work-up method for a definite diagnosis of IBD included ileocolonoscopy. Results: The 14 patients were divided into the following five groups: ulcerative colitis (n=4, 29%), intestinal Behcet’s disease (n=3, 21%), intestinal tuberculosis (n=2, 14%), malignancy (n=2, 14%), and no abnormal findings with colonoscopy (n=3, 21%). A PET-CT based-diagnosis of IBD correlated with a colonoscopic diagnosis in nine cases (64.3%), but the matching ratio of the distribution of lesions between PET-CT findings and colonoscopic findings was only 18.1% (2/11). Conclusions: The utility of PET-CT in the diagnosis of IBD requires further evaluation.ope

Recurrent Coccidioidomycosis Manifesting as Osteomyelitis in Korea

Coccidioidomycosis is a fungal infection that results from inhaling the airborne arthroconidia of the Coccidioides species. It is an endemic disease in the southwest part of North America and rarely diagnosed in Korea. As tourism to endemic areas and the number of immunocompromised patients have been increasing, the incidence of this infection has increased in non-endemic areas. Treatment is usually successful with antifungal agents; however, recurrence is common. It is difficult to decide when to discontinue the antifungal treatment especially in non-endemic areas where doctors are not familiar with the disease. We report a case of recurrent coccidioidomycosis manifesting as osteomyelitis after the treatment of the patient for disseminated coccidioidal infection. The complement fixation test was a useful tool for the assessment of patient response and to evaluate suspected recurrenceope

A Case of Henoch-Shonlein Purpura Caused by Rifampin

Rifampin is one of the first line drugs for treating tuberculosis, but it might be associated with serious adverse effects, including renal failure. We report here on a case of a 57-year-old patient who developed Henoch-Shonlein purpura during antituberculosis therapy that included rifampin. The patient converted to negative on the AFB smear for tuberculosis two weeks after the initial administration of antituberculosis medication. After treatment for 60 days, this patient was diagnosed with Henoch-Shonlein purpura by the purpura lesion on the lower legs, the leukocytoclastic vasculitis, the renal impairment and the pathological examination. After stopping rifampin, the skin lesions disappeared in about 10 days and his renal function gradually improved. This case study showed that Henoch-Schonlein purpura can be caused by rifampin during antituberculosis therapy and we recommend that the use of rifampin should be restrained when clinical symptoms of Henoch-Shonlein purpura are observedope

Thiopurine 약물치료를 받고 있는 한국의 염증성 장질환 환자들의 Thiopurine Methyltransferase와 Inosine Triphosphate Pyrophosphatase의 유전자형과 장기간 치료 반응과의 상관관계

Dept. of Medicine/석사[한글] [영문]Background and Aims: There is a lack of research describing associations between thiopurine methyltransferase (TPMT)/inosine triphosphate pyrophosphatase (ITPA) genotypes or phenotypes and long-term clinical outcomes after thiopurine treatment. We investigated whether TPMT/ITPA genotypes and TPMT activity would predict long-term clinical response in Korean patients with inflammatory bowel diseases (IBD) undergoing thiopurine treatment.Methods: A total of 113 patients with IBD in whom thiopurine treatment was indicated were enrolled and categorized by TPMT and ITPA genotypes and TPMT enzyme activity. Long-term follow-up clinical data for these patients were analyzed with specific focus on disease relapse.Results: Seventy-eight of 113 patients (69.0%) using thiopurines achieved remission and were included in the analysis. There were no significant differences in disease relapse-free survival between wild and mutant types of TPMT (p=0.690) or ITPA (p=0.403) according to the results of log rank analysis. The mean TPMT activity in the ‘non-relapsers’ (n=27) was significantly higher than in ‘relapsers’ (n=51) (p = 0.001).Conclusions: Our study suggests that TPMT and ITPA genotypes or TPMT activity may not affect rates of disease relapse in Korean IBD patients treated with thiopurines. Further studies are indicated to appropriately guide clinicians formulating individualized treatments for IBD patients requiring thiopurine therapy.ope

주택재개발구역의 건축제한에 따른 주거지변화 연구

학위논문(석사) --서울대학교 환경대학원 :환경계획학과(도시 및 지역계획전공),2010.2.Maste