• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권6호
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• pp.481-489
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• 2010

Introduction: TLR-5, a member of the toll-like receptor (TLR) family, is a element of the type I transmembrane receptors, which are characterized by an intracellular signaling domain homolog to the interleukin-1 receptor. These receptors recognize microbial components, particularly bacterial flagellin. All-trans retinoic acid (atRA, tretinoin), a natural metabolite of vitamin A, acts as a growth and differentiation factor in many tissues, and is also needed for immune functions. In this study, THP-1 human macrophage-monocytes were used to examine the mechanisms by which atRA regulated the expression of TLR-5. Because the molecular mechanism underlying this regulation at the transcriptional level is also unclear, this study examined which putative transcription factors are responsible for TLR-5 expression by atRA in immune cells. Materials and Methods: This study examined whether atRA induces the expression of TLR-5 in THP-1 cells using reverse transcription-polymerase chain reaction (RT-PCR), and which transcription factors are involved in regulating the TLR-5 promoter in RAW264.7 cells using a reporter assay system. Western blot analysis was used to determine which signal pathway is involved in the expression of TLR-5 in atRA-treated THP-1 cells. Results: atRA at a concentration of 10 nM greatly induced the expression of TLR-5 in THP-1 cells. Human TLR-5 promoter contains three Sp-1/GC binding sites around -50 bp and two NF-kB binding sites at -380 bp and -160 bp from the transcriptional start site of the TLR-5 gene. Sp-1/GC is primarily responsible for the constitutive TLR-5 expression, and may also contribute to NF-kB at -160 bp to induce TLR-5 after atRA stimulation in THP-1 cells. The role of NF-kB in TLR-5 expression was further confirmed by inhibitor pyrrolidine dithiocarbamate (PDTC) experiments, which greatly reduced the TLR-5 transcription by 70-80%. Conclusion: atRA induces the expression of the human TLR-5 gene and NF-kB is a critical transcription factor for the atRA-induced expression of TLR-5. Accordingly, it is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents of infectious diseases. atRA and various synthetic retinoids have been used therapeutically in human diseases, such as leukemia and other cancers due to the antiproliferative and apoptosis inducing effects of retinoids. Therefore, understanding the molecular regulatory mechanism of TLR-5 may assist in the design of alternative strategies for the treatment of infectious diseases, leukemia and cancers.

• Clinical and Experimental Pediatrics
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• 제54권3호
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• pp.95-105
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• 2011

Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

• 정신신체의학
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• 제8권1호
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• pp.31-45
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• 2000

연구목적 : 여성 및 남성 탈모중의 개인적 특성이나 탈모양상, 정신의학적특성, 동반 신체질환 및 치료 방법에 관한 비교 분석을 통해 여성 탈모증의 치료 및 예방 지침을 수립하기 위해 연구를 시도 하였다. 방법 : 1998년 1월부터 12월까지 중앙대학교 용산병원 피부과에 내원하여 정신과로 의뢰된 여성 탈모증 환자 51명을 연구집단으로, 남성 탈모증환자 42명을 대조군으로 선정하여 남녀별 차이를 비교 분석하였다. 수집된 자료는 SPSS-$PC^+$ 9.0V 프로그램을 통해 자료 처리를 하였고, 집단간의 차이는 교차 분석 및 변량 분석을 통해 비교 분석하였다. 결과 : 1) 여성일수록 남성에 비해 경제 수준이나 교육 수준이 낮고, 하류 직종에 종사하며, 부친이 무직자가 많고, 형제 자매 수가 많으며, 여자형제만 있는 비율이 높다. 2) 여성일수록 피부과 내원빈도가 많고, 최근 두정부나 전두부 탈모가 많으며, 여성가족 중에 탈모 경험자가 많은 반면에 남성 가족중에는 탈모자가 적고, 후두부 탈모가 적으며, 손톱의 변화는 적다. 3) 여성일수록 가정내 갈등이나 경제적 변화로 인해 스트레스를 받고, 가정내 갈등이나 내성적 성격으로 인해 갈등을 겪는 반면 직장문제나 건강 변화 등 생활 변동을 겪거나, 작업 수행 능력의 부진으로 인한 갈등은 적고 직장 적응에 있어 어려움을 겪는 비율도 낮다. 4) 여성일수록 우울증이나 전환장애가 많고, 불안 증상들이나 우울 증상들을 흔히 호소하며, 불안수준이 높은 반면 신체화증상이나 강박증상은 덜 호소하며, 불안장애는 적다. 5) 여성일수록 남성에 비해 내향화 성향이나 허구 성향 억압 성향 여성화 성향이 높다. 6) 여성일수록 관절염이나 비뇨생식계장애가 많은 반면 위장관장애나 지루성피부염은 적다. 7) 여성일수록 etizolam이나 tretinoin은 많이 사용하는 반면 향정신성 의약품은 적게 사용하며, 특히 clotiazepam이나 prednicarbonate를 적게 사용한다. 결론 : 여성 탈모증 환자는 남성 환자에 비해 우울증이 많고, 불안 및 우울 증상을 흔히 호소하며, 가정 문제로 인해 발병하고, 내향화 성향이나 허구 성향, 억압 성향, 여성화 성향이 높다. 이 결과는 여성 환자가 남성 환자에 비해 더 심각한 정신병리를 보여 준다는 것을 의미하고, 여성 탈모의 예방 및 치료를 위해 정신과적 개업이 필요함을 말해 주고 있다. 따라서 피부과 의사들은 병발하는 정신장애에 대해 깊은 관심을 갖고, 정신과와 피부과가 공동 치료 계획을 세워야 한다.