• Journal of Applied Biological Chemistry
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• 제60권3호
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• pp.227-234
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• 2017

염증성 장 질환에 일반적으로 사용되는 설파살라진은 고용량 및 장기 섭취 후 다양한 부작용이 있다. 본 연구에서는 TNBS로 유발된 마우스 대장염 모델에서 설파살라진, 육계와 시호 복합 추출물의 항염증 및 세포 자멸 개선효과를 확인하고자 하였다. 실험은 정상군, TNBS 대조군, Sulfasalazine (30 mg/kg)군, Sulfasalazine (60 mg/kg)군, Sulfasalazine (30 mg/kg)+육계 및 시호 혼합 (30 mg/kg)군, 총 5개의 군으로 나누었으며, 7일간 경구투여 하였다. 염증 및 세포 자멸 단백질은 western blot을 통해 발현량을 확인하였다. SCB 투여는 염증 단백질 및 세포 자멸과 관련된 단백질의 억제에 유의한 효과를 나타냈다. 이러한 결과로 보아 설파살라진, 육계와 시호 복합 추출물은 염증과 세포 자멸의 억제를 통해 염증성 장 질환을 개선시킬 수 있으며, 염증성 장 질환의 치료 대안 가능 물질로 사료되는 바이다.

• Advances in pediatric surgery
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• 제16권2호
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• pp.117-125
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• 2010

Unreduced small bowel intussusception requires operative treatment although the rate of spontaneous reduction is 60 to 70 %. The aim of this study is to compare clinical characteristics and outcome between spontaneous reduction and operation group and to analyze factors related to decisions to treat small bowel intussusceptions. The records of 25 patients with small bowel intussusceptions treated in Seoul National University Children's Hospital from January 1999 to August 2009 were reviewed respectively. Spontaneous reduction group (n=12, 48 %) had signs and symptoms of vomiting, abdominal pain, currant jelly stool, abdominal distension, fever, increased CRP but no rebound tenderness. One of them had been diagnosed with Henoch-Schonlein purpura and no one displayed pathologic leading point by image study. Operation group (n=13, 52 %) consisted of patients who had primary surgery. Their signs and symptoms were similar to spontaneous reduction group. Seven of them had underlying diseases such as Crohn' disease, ALL, Lymphoma, Peutz-Jeghers syndrome (n=3), post-transplanted state of liver and 2 of them displayed Peutz-Jeghers polyp and Meckel's diverticulum as pathologic leading point by preoperative ultrasonography. Mean relieve interval (interval between onset of symptoms and reduction/operation) was 1.78 days in spontaneous reduction group and 2.25 days in operation group (p=0.341). Seven of operation group had manual reduction and 6 out of 7 received segmental resection of the small bowel. No one of them underwent manual reduction and all of them underwent segmental resection were found to have pathologic leading points [Peutz-Jeghers polyp (n=3), Meckel's diverticulum (n=2), lymphoma (n=1)] during operation. In conclusion, 48% of small bowel intussusceptions resolved spontaneously. Patients' symptoms and relieve intervals were not related to the operative decisions. We therefore recommend significant factors for determining treatment plan such as change of clinical symptoms, underlying disease or pathologic leading point by imaging.

• 대한의생명과학회지
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• 제15권3호
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• pp.261-263
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• 2009

Methylprednisolone is a synthetic glucocorticoid which is usually taken intravenously for many neurosurgical diseases which cause edema including brain tumor, and trauma including spinal cord injury. Methylprednisolone reduces swelling and decreases the body's immune response. It is also used to treat many immune and allergic disorders, such as arthritis, lupus, psoriasis, asthma, ulcerative colitis, and Crohn's disease. To identify genes expressed during methylprednisolone treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up- or down-regulated genes) which are methylprednisolone differentially expressed in neurons. Lipocalin 3 is the gene most significantly increased among 772 up-regulated genes (more than 2 fold over-expression) and Aristaless 3 is the gene most dramatically decreased among 959 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Fgb, Thbd, Cfi, F3, Kngl, Serpinel, C3, Tnfrsf4 and Il8rb are involved stress-response gene, and Nfkbia, Casp7, Pik3rl, I11b, Unc5a, Tgfb2, Kitl and Fgf15 are strongly associated with development. Cell cycle associated genes (Mcm6, Ccnb2, Plk1, Ccnd1, E2f1, Cdc2a, Tgfa, Dusp6, Id3) and cell proliferation associated genes (Ccl2, Tnfsf13, Csf2, Kit, Pim1, Nr3c1, Chrm4, Fosl1, Spp1) are down-regulated more than 2 times by methylprednisolone treatment. Among the genes described above, 4 up-regulated genes are confirmed those expression by RT-PCR. We found that methylprednisolone is related to expression of many genes associated with stress response, development, cell cycle, and cell proliferation by DNA microarray analysis. However, We think further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by methylprednisolone. The resulting data will give the one of the good clues for understanding of methylprednisolone under molecular level in the neurons.

• IMMUNE NETWORK
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• 제5권4호
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• pp.205-214
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• 2005

Background: We examined global gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with ulcerative colitis (DC), and tested whether the identified genes with the altered expression might be associated with susceptibility to UC. Methods: PBMCs from 8 UC and 8 normal healthy (NH) volunteers were collected, and total RNAs were subjected to the human 8.0K cDNA chip for the micro array analysis. Real time-PCR (RT-PCR) was performed to verify the results of micro array. One hundred forty UC patients and 300 NH controls were recruited for single nucleotide polymorphism (SNP) analysis. Results: Twenty-five immune function-related genes with over 2-fold expression were identified. Of these genes, two chemokines, namely, CXCL1 and CCL20, were selected because of their potential importance in the evocation of host innate and adaptive immunity. Four SNPs were identified in the promoter and coding regions of CXCL1, while there was no significant difference between all patients with UC and controls in their polymorphisms, except minor association at g.57A>G (rs2071425, p=0.02). On the other hand, among three novel and one known SNPs identified in the promoter region of CCL20, g. -1,706 G>A (p=0.000000055), g. -1,458 G>A (p=0.0048), and g. -962C>A (p=0.0006) were found to be significantly associated with the susceptibility of Uc. Conclusion: Altered gene expression in mononuclear cells may contribute to IBD pathogenesis. Although the findings need to be confirmed in other populations with larger numbers of patients, the current results demonstrated that polymorphisms in the promoter region of CCL20 are positively associated with the development of Uc.

• Journal of Korean Medical Science
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• 제33권47호
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• pp.292.1-292.10
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• 2018

Background: We investigated the incidence of active tuberculosis among patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF) inhibitors, with or without latent tuberculosis infection (LTBI). Methods: The study was performed at a Korean tertiary referral center between January 2011 and June 2017. In total, 740 patients with IBD who underwent LTBI screening tests and were followed-up for ${\geq}1$ year after TNF inhibitor treatment initiation were enrolled. LTBI was detected on the basis of tuberculin skin test results, interferon-gamma release assay results, chest X-ray findings, and previous tuberculosis treatment history. The patients were classified into LTBI (n = 84) or non-LTBI (n = 656) group. The risk of developing tuberculosis in each group was assessed on the basis of standardized incidence ratio (SIR) and 95% confidence interval (CI) for active tuberculosis. Results: Mean patient age was 33.1 years, and patients with Crohn's disease were predominant (80.7%). Within 1 year after the initiation of TNF inhibitor treatment, 1 patient in the LTBI group (1/84; 1.2%) and 7 patients in the non-LTBI group (7/656; 1.1%) developed active tuberculosis. The overall 1-year incidence of tuberculosis among the patients was significantly higher than that among the general population (SIR, 14.0; 95% CI, 7.0-28.0), and SIR was not affected by LTBI status (LTBI group: 14.5, 95% CI, 2.0-102.6; non-LTBI group: 14.0, 95% CI, 6.7-29.4). Conclusion: Patients with IBD undergoing TNF inhibitor treatment showed a higher 1-year incidence of tuberculosis than the general population irrespective of LTBI status.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제12권2호
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• pp.177-182
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• 2009

목 적: 소아에서 다양한 원인에 의해 발생한 대장염에서 점막의 형태학적 변화와 세포 접합에 다양한 변화가 있으리라 예상되어 세포 간의 결합을 유지하는 E-cadherin의 변화를 살펴보았다. 방 법: 1998년 1월부터 2003년 8월까지 부산대학교병원 소아청소년과에서 하부 위장관 내시경술과 대장점막 조직 검사를 통해 대장염으로 진단된 39명을 대상으로 하였다. 파라핀 블록에서 면역조직화학염색법을 이용하여 E-cadherin의 세포 내 발현을 조사하였다. 주변의 정상 조직과 비교하여 E-cadherin의 발현이 동일한 강도와 양상을 가진 세포가 50% 이상인 경우를 정상으로 판정하였고, 발현이 정상인 세포가 50% 미만이거나 염색 분포의 이상이 있거나 전혀 염색되지 않은 경우를 이상으로 판정하였다. 결 과: 1) 본 연구에서 비특이성 대장염 15예(38.5%), 크론병 7예(17.9%), 감염성 대장염 5예(12.8%), 음식 단백 과민성 직결장염 5예(12.8%), 궤양성 대장염 3예(7.7%), Henoch-Schonlein purpura 대장염 2예(5.1%), 그외 베체트병, 허혈성 대장염 1예가 포함되었다. 2) 모든 종류의 대장염에서 상피세포 E-cadherin 발현 감소가 관찰되었으며, 77%의 대상 표본에서 E-cadherin 발현감소가 있었다. 3) 활동성 염증이 심한 부위에서 Ecadherin 발현 감소가 현저하였으며 병변부에서 떨어진 상피세포에서는 정상 발현을, 궤양 주위나 재생 상피가 있는 부위는 심한 발현 감소를 보였다. 결 론: 모든 종류의 염증성 대장 질환에서 E-cadherin 발현 감소가 있었다. 이러한 변화는 염증과 궤양이 있는 부위에서 상피세포 접합을 느슨하게 함으로써 상피세포의 재생을 위한 세포의 이동을 용이하게 하기 위한 작용이라고 판단된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2545-2548
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• 2016

Background: There is growing evidence that there are differences in histological and genetic characteristics along with clinical behavior between right- and left-sided colon carcinomas. We have compared various parameters of the two types and assessed associations of the results with prognosis in patients in Pakistan. Materials and Methods: We reviewed 200 cases from our institutional database; 100 cases of right-sided and 100 cases of left-sided colon cancer. Parameters including age, gender, TNM stage, histological features and clinical outcome were analyzed. Results: The patients with right-sided colon cancer were significantly older as compared to their counterparts with left-sided cancer. They presented with a lumbar mass rather than symptoms of obstruction and perforation as seen in left-sided colon cancers, and the histology showed higher percentage of poorly differentiated tumors with advanced pT stage. Moreover, Crohn's-like reactions, intra tumoral lymphocyte responses and other poor prognostic factors like lymph vascular invasion and perineural invasion were more common in right-sided cancers. Conclusions: We found that right- and left-sided colon cancers are different from each other in terms of clinical presentation, histology and clinical behavior. Right-sided colon cancers are more aggressive and are associated with poorer clinical outcome as compared to left sided colon cancers in our population.

• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.169-175
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• 2014

Human organic cation/carnitine transporter 1 (OCTN1) plays an important role in the transport of drugs and endogenous substances. It is known that a missense variant of OCTN1 is significantly associated with Crohn's disease susceptibility. This study was performed to identify genetic variants of the OCTN1 promoter in Korean individuals and to determine their functional effects. First, the promoter region of OCTN1 was directly sequenced using genomic DNA samples from 48 healthy Koreans. OCTN1 promoter activity was then measured using a luciferase reporter assay in HCT-116 cells. Seven variants of the OCTN1 promoter were identified, two of which were novel. There were also four major OCTN1 promoter haplotypes. Three haplotypes (H1, H3, and H4) showed decreased transcriptional activity, which was reduced by 22.9%, 23.0%, and 44.6%, respectively (p<0.001), compared with the reference haplotype (H2). Transcription factor binding site analyses and gel shift assays revealed that NF-Y could bind to the region containing g.-1875T>A, a variant present in H3, and that the binding affinity of NF-Y was higher for the g.-1875T allele than for the g.-1875A allele. NF-Y could also repress OCTN1 transcription. These data suggest that three OCTN1 promoter haplotypes could regulate OCTN1 transcription. To our knowledge, this is the first study to identify functional variants of the OCTN1 promoter.

• 대한약침학회지
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• 제20권1호
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• pp.10-17
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• 2017

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

• Tuberculosis and Respiratory Diseases
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• 제75권6호
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• pp.238-243
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• 2013

Background: The aim of our study was to evaluate the "diagnosis changed" rate in patients notified as tuberculosis (TB) on the Korean TB surveillance system (KTBS). Methods: A total of 1,273 patients notified as TB cases on the KTBS in one private tertiary hospital in 2011 were enrolled in the present study. Patients were classified into three groups: "diagnosis maintained", "diagnosis changed" (initially notified as TB, but ultimately diagnosed as non-TB), and "administrative error" (notified as TB due to administrative errors). Results: Excluding 17 patients in the "administrative error" group, the "diagnosis maintained" and "diagnosis changed" groups included 1,097 (87.3%) and 159 patients (12.7%), respectively. Common causes of "diagnosis changed" were nontuberculous mycobacterial (NTM) disease (51.7%, 61/118), and pneumonia (17.8%) in cases notified as pulmonary TB, and meningitis (19.5%, 8/41) and Crohn's disease (12.2%) in cases notified as extrapulmonary TB. Being older than 35 years of age (odds ratio [OR], 2.18) and a positive acid-fast bacilli stain (OR, 1.58) were positive predictors and a TB-related radiological finding (OR, 0.42) was a negative predictor for a "diagnosis changed" result via multivariate logistic regression analysis in pulmonary TB cases. Conclusion: Because of a high "diagnosis changed" rate in TB notifications to the KTBS, the TB incidence rate measured by the KTBS may be overestimated. Considering the worldwide trend toward increased NTM disease, the "diagnosis changed" rate may increase over time. Thus, when reporting the annual TB notification rate in Korea, the exclusion of "diagnosis changed" cases is desirable.