• Clinical and Experimental Pediatrics
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• 제51권1호
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• pp.67-72
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• 2008

목 적 : 본 연구는 HLA가 일치하는 부모로부터 동종조혈모세포이식을 시행받은 소아의 이식 결과를 분석하고자 하였다. 방 법 : 1999년 4월부터 2005년 10월까지 성모병원 조혈모세포이식센터에서 급성 백혈병으로 1차 관해 후 HLA가 일치된 부모로부터 조혈모세포이식을 시행받은 환아 7명(급성 림프모구성백혈병 4명, 급성 골수성백혈병 3명)을 대상으로 하였다. 이식 시 중앙연령은 5세(범위, 1-11세; 남아 2명, 여아 5명), 공여자의 중앙연령은 35세(범위, 30-41세; 남자 5명, 여자 2명)이었다. 이식 후 대상 환아의 생착, 급성이식편대숙주병, 만성이식편대숙주병, 이식관련 사망, 재발, 이식관련 합병증과 생존율 등을 분석하였다. 결 과 : 이식부터 마지막 추적관찰까지 중앙기간이 69.5개월(범위, 18.8-96.5개월)이었다. 이식을 받은 7명의 환아들은 모두 생착이 되었고 호중구와 혈소판의 생착은 이식 후 각각 11일(범위, 10-16일)과 26일(범위, 13-39일)이었다. Grade II의 급성 이식편대숙주병은 3명(43%), grade III의 급성 이식편대숙주병은 1명(14%)에서 발생하였다. 광범위 만성이식편대숙주병은 2명(28%), 제한적 만성이식편대숙주병은 1명(14%)에서 발생하였다. 이식 후 재발은 1명(14%)이었고 이식관련 사망은 1명(14%)이었다. 대상 환아의 이식 후 5년 전체 생존율은 $83{\pm}15%$이었다. 결 론 : 소아 급성 백혈병에서 HLA가 일치하는 부모자식간 동종조혈모세포이식의 결과는 HLA가 일치하는 형제간 조혈모세포이식의 결과와 비견할 수 있으며 동종조혈모세포이식이 필요한 환아에서 형제뿐만이 아니라 부모의 HLA를 검사하면 조혈모세포 공여자 선정의 가능성이 높아진다.

• Parasites, Hosts and Diseases
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• 제40권4호
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• pp.165-172
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• 2002

Collaborative studies have identified some genetic factors contributing to the development of severe forms of malaria and schistosomiasis. In Thailand, the $TNF-{\alpha}{\;}5'-flanking$ region shows biallelic polymorphic sites at nucleotides -238, -308, -857, -863, and -1031, and seven alleles have been identified in patients from Myanmar. We found that the TNF promoter (TNFP)-D allele was significantly associated with cerebral malaria in populations from Karen (P < 0.0001. OR ＝ 124.86) and ethnic Burma (P < 0.0001, OR = 34.50) . In China, we have identified two major genes related to the severity of liver fibrosis, one an HLA class II gene, and the other the IL-13 gene. The frequency of the HLA- DRB5*0101 allele and that of the IL-13 promoter A/A (IL- l3P- A/A) genotype were elevated in fibrotic patients, although the two genes are located on different chromosomes, chromosomes 6p and 5q, respectively Subjects with both genotypes had odds ratios (OR = 24.5) much higher than the sum of the ratios for each individual genotype (OR ＝ 5.1,95% Confidence Interval 1.3-24.7 for HLA-DRB5*0101, OR ＝ 3.1 95% CI 1.5 - 6.5 for IL-l3P-A/A). That the effects of the two susceptibility markers are synergistic rather than additive, strongly suggests that the pathogenic Th2 response directly influences the prognosis of post-schistosomal liver fibrosis.

• 한국시뮬레이션학회논문지
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• 제23권2호
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• pp.57-64
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• 2014

본 논문에서는 항공 교전 시뮬레이션을 위한 모델을 구축함에 있어서 분산 시스템 상의 합성전장환경 기반으로 구성되는 시스템 구축을 위한 프레임워크를 제안한다. 제안된 프레임워크는 HLA (High Level Architecture)/RTI (Run-Time Infrastructure) 기반의 분산 시스템 상에서 합성전장환경을 구축하여 항공 교전 시뮬레이션 모델에 환경의 영향을 반영하기 위한 시스템을 설계한다. 항공 전투에서 환경은 탐지체계 및 기동체계 등에 영향을 주기 때문에 시뮬레이션에서 그 영향을 반영할 필요가 있다. 그러나 교전급 시뮬레이션에서 요구하는 무기체계의 복합적 운용에 관련된 프레임워크 연구는 기존에 미흡하였고, 이로 인해 환경 데이터를 기반으로 시뮬레이션에 환경 영향을 반영하는 교전급 시뮬레이션 시스템의 구축은 난해함을 갖는다. 본 논문은 이와 같은 난해함을 해결하기 위한 프레임워크를 제안하고, 제안된 프레임워크를 기반으로 예제 시스템을 구축하는데 목적을 둔다.

• 한국시뮬레이션학회논문지
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• 제26권2호
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• pp.1-8
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• 2017

High Level Architecture (HLA)는 완성된 시뮬레이터를 연동함으로써 재사용성을 높이고 분산된 이기종 시뮬레이터간의 연동성을 확보하고자 제정된 연동 표준으로, Runtime Infrastructure (RTI)로 구현되어 다양한 시뮬레이터간의 연동 시뮬레이션을 중개한다. 이러한 연동 시뮬레이션 관련 연구는 연동 대상이 되는 시스템이 점점 복잡해짐에 따라 시뮬레이터간의 연동을 넘어 연동된 페더레이션 간의 연동으로 발전하고 있다. 그러나 기존의 연구들은 객체 모델 통합에 대한 고민이 없었기 때문에 객체 모델이 동일한 표준 형식을 따르며 차이점이 존재하지 않아 쉽게 통합될 수 있다고 가정하고 진행되었다. 그러나 다양한 HLA 표준에 기초한 페더레이션들이 이미 구현되어 있기 때문에 객체 모델의 형식에 차이점이 있어 기계적인 객체 모델 통합이 불가능하고, 실제로는 같은 객체/속성에 대해 다르게 기술되어 있을 가능성이 많다. 또한 모든 객체를 통합하여 공개했을 때에는 보안성의 문제도 존재한다. 따라서 본 논문은 이러한 문제를 해결하는 페더레이션 연동을 위한 객체 모델 통합 프로세스를 제안한다. 제안하는 객체 모델 통합 프로세스는 서로 다른 표준을 따르는 객체 모델 간의 통합 방법을 제안하고, 객체간의 서로 다른 이름/특성 문제를 해결하며, 보안객체를 제외하는 기능을 담고 있다. 본 연구를 통하여 페더레이션 연동 기술이 실제적으로 적용될 때에 각 페더레이션의 연동성과 재사용성을 향상시킬 수 있을 것으로 기대한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1247-1251
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• 2012

Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5399-5403
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• 2012

Aims and Background: Human leukocyte antigen-G and interleukin-2 receptor play pivotal roles in the proliferation of lymphocytes, and thus generation of immune responses. Their overexpression has been evidenced in different malignant hematopoietic diseases. This study aimed to validate serum soluble human leukocyte antigen-G (sHLA-G) and serum soluble interleukin-2 receptor (sIL-2R) as an additional tool for the diagnosis and follow up of acute lymphoblastic leukemia (ALL). Subjects and Methods: Both markers were determined by ELISA in the serum of 33 ALL pediatric patients before treatment and after intensification phase of chemotherapy as well as in the serum of 14 healthy donors that were selected as a control group. Results: ALL patients showed abnormal CBC and high serum lactate dehydrogenase, which were improved after chemotherapy. Also, there was a non-significant increase in serum sHLA-G in ALL patients compared with the control group. However, after chemotherapy, sHLA-G was increased significantly compared with before treatment. On the other hand, serum sIL-2R in ALL patients was increased significantly compared with the control group. After chemotherapy, sIL-2R decreased significantly compared with before treatment. Conclusions: From these results it could be suggested that measurement of serum sHLA-G might be helpful in diagnosis of ALL, while sIL-2R might be useful in diagnosis and follow-up of ALL in pediatric patients.

• 한국시뮬레이션학회논문지
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• 제11권2호
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• pp.31-43
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• 2002

The High Level Architecture(HLA) for modeling and simulation was developed as means of facilitating interoperability among simulations and promoting reuse of simulations and their components. The purpose of this paper is to provide a summary of the latest release of the HLA concept, supporting utilities and develop the prototyped Transportation Movement Management(TMM) federation. To obtain this goal, the Federation Development and Execution Process(FEDEP) is being applied to development of TMM federation will consist of three federates. This paper outlines the rationale of our approach, describes the application of the FEDEP in the development of the federation, and provides the current status of the federation development. The resulting federation shows complete interoperability among simulation components in the TMM federation and satisfactory simulation outputs. We present a description and process of the federation and the lessons learned with the process utilization for federation development and execution. Furthermore, the issues in establishing a HLA based federation across multiple legacy simulations are discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2491-2497
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• 2016

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; p< $3.5{\times}10^{-4}$), DRB1*14-DQB1*0501 (OR=6.51; p<0.039) and A*11-B*07 (OR=3.95; p<0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; p<0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ${\beta}9$ and ${\beta}37$ and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.

• IMMUNE NETWORK
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• 제2권4호
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• pp.242-247
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• 2002

Background: Tumor necrosis factor-alpha (TNF-$\alpha$) is known to play an important role in various conditions such as inflammation, autoimmunity, apoptosis, insulin resistance and sleep induction. Five single nucleotide polymorphisms (SNPs) have been known to affect the transcriptional activities of TNF-$\alpha$: -1,031T/C, -863C/A, -857C/T, -308G/A and -238G/A. Methods: We have investigated 5 SNPs of the promoter region of TNF-$\alpha$ gene, the distribution of 5-locus TNF-$\alpha$ haplotypes, and their haplotypic associations with previously typed HLA-A, -B and -DRB1 loci in 107 healthy unrelated Koreans. TNF-$\alpha$ SNPs were typed using PCR-single-strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. Results: The allele frequencies of -1,031C, -863A, -857T, -308A, and-238A, which are known as the high-producer-type, were 19.3%, 15.9%, 14.0%, 5.9%, and 2.9%, respectively. The frequency of -308A allele, known to be associated with autoimmune diseases, was 5.9% in Koreans which was lower than Caucasians (14~17%) and somewhat higher than Japanese (1.7%). Five most common TNF-$\alpha$ haplotypes (-1,031/-863/-857/-308/-238) comprised over 95% of total haplotypes: TCCGG (58.4%), CACGG (14.8%), TCTGG (13.7%), TCCAG (5.3%), and CCCGA (3.1%). Strong positive associations (P<0.001) were observed between TCCGG and B62; between CACGG and B51, $DRB1^*0901$; between TCTGG and B35, B54, B59, $DRB1^*1201$; and between TCCAG and A33, B58, $DRB1^*0301$, $DRB1^*1302$. Five most common extended haplotypes (>3%) comprised around 16% of total haplotypes: A33-B58-TCCAG-$DRB1^*1302$, A24-B52-TCCGG-$DRB1^*1502$, A33-B44-TCCGG-$DRB1^*1302$, A24-B7-TCCGG-$DRB1^*0101$, and A11-B62-TCCGG-$DRB1^*0406$. The distribution of extended HLA and TNF-$\alpha$ haplotypes showed that most of HLA haplotypes were almost exclusively associated with particular TNF-$\alpha$ haplotypes. Conclusion: The results obtained in this study would be useful as basic data for anthropologic studies and disease association studies in Koreans.

• BMB Reports
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• 제32권6호
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• pp.529-534
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• 1999

Asymmetric PCR and single-strand conformation polymorphism (SSCP) methods were combined to analyze human leukocyte antigen (HLA)-DRB allele polymorphism. Asymmetric PCR amplification was applied to generate single-stranded DNA (ssDNA) using the nonradioactive oligonucleotide primers desinged for the polymorphic exon 2 region. The conformational differences of ssDNAs, depending on the allele type, were analyzed by nondenaturing polyacrylamide gel electrophoresis and visualized by ethidium bromide staining. The ssDNAs were clearly separated from double-stranded DNA without interference and obviously migrated depending on their allele type. This method was applied to the genomic DNA either from homozygous or from heterozygous cell lines containing the DR4 allele as template DNA using DR4-specific primers, and satisfying results were obtained. Compared to the standard PCR-SSCP method, this asymmetric PCR-SSCP method has advantages of increased speed, reproducibility, and convenience. Along with PCR-SSP or sequence-based typing, this method will be useful in routine typing of HLA-DRB allele.