매끄럽지 않은 영역에서 정의되고 측정가능한 비선형 계수 함수를 가지는 타원형 및 포물형 편미분 방정식

학위논문 (박사)-- 서울대학교 대학원 : 수리과학부, 2015. 8. 변순식.We study elliptic and parabolic equations with measurable nonlinearities in nonsmooth domains. We establish an optimal global $W^{1,p}$ estimate under the condition that the associated nonlinearity is allowed to be merely measurable in one variable but has a sufficiently small BMO semi-norm in the other variables, while the underlying domain is sufficiently flat in the Reifenberg sense that the boundary of the domain is locally trapped between two narrow strips.Abstract i 1 Introduction 1 2 Elliptic equations 5 2.1 Definitions and main result 5 2.2 Preliminaries 8 2.3 Lipschitz regularity for limiting equations 13 2.3.1 Interior Lipschitz regularity for limiting equations 14 2.3.2 Boundary Lipschitz regularity for limiting equations 17 2.4 Comparison estimates 22 2.4.1 Interior comparison estimates 22 2.4.2 Boundary comparison estimates 25 2.5 Global estimates in Reifenberg flat domains 32 3 Parabolic equations 44 3.1 Definitions and main result 44 3.2 Preliminaries 48 3.3 Lipschitz regularity for limiting equations 53 3.3.1 Interior Lipschitz regularity for limiting equations 54 3.3.2 Boundary Lipschitz regularity for limiting equations 65 3.4 Comparison estimates 80 3.4.1 Interior comparison estimates 81 3.4.2 Boundary comparison estimates 83 3.5 Global estimates in Reifenberg flat domains 92 Abstract (in Korean) 108Docto

Studies on the effects of UV irradiation on melanocytes after application of various phototoxic drugs

의학과/석사[영문] [한글] 백반증의 치료로서 병소의 크기가 작을 때나 환자의 연령이 낮을 때 국소광화학요법이 널리 사용되나 색소 침착에 필요한 최저 광독량을 유발하는 자외선 노출시간의 조절이 매 우 힘들어서 치료도중 홍반이나 수포형성이 일어날 수 있으므로 부작용이 적고 효과가 좋 은 약제의 선택과 적절한 농도의 선정이 중요하다. 8-Methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 및 4,5, 8,-trimethylpsorale n (TMP)은 광화학요법시 사용되는 광독성 약물들로서 이들간의 색소침착효과에 대한 비교 연구는 드물다. 본 연구에서는 성숙된 수컷 흑색쥐 (C 57 BL mouse) 116마리를 대상으로8-MOP, 5-MOP, TMP 각각에 대해 농도0.02%, 0.1%, 0.5%를 도포한 9군과 기저용액만을 도포한 대조군으로 나누고 약물 도포 3O분후에 UVA를 1주에 2회씩 7주간 조사하였다. UVA조사량은 첫주는1 회 150mJ/cm**2이며, 둘째주는 200mJ/cm**2, 셋째주는 250mJ/cm**2, 넷째주 이상은 300mJ /cm**2이었다. UVA조사후 1주, 3주, 5주, 7주에 피부조직을 생검하여 Split-Dopa 염색을 시행한 후 색소세포의 변화를 관찰하기 위하여 색소세포의수, 면적, 둘레 길이를 측정하 여 다음과 같은 결과를 얻었다. Studies on the effects of UV irradiation on melanocytes after application of various phototoxic drugs You Chan Kim Deparenent of Medical Science The Graduate School, Yonsei University (Directed by Professor Yoon-Kee Park, M.D.) For treatment of vitiligo in patients of young age or with small areas of involvements topical photochemotherapy is widely used. However, it is very difficult to control the amount of time of ultraviolet exposure for induction of the minimum phototoxicity necessary for pigment deposition. Therefore, during ireatrnent of vitiligo, erythema or vesicle formation can occur, which necessitates the selection of drugs with few complications and good effect as well as the proper concentration. 8-Methoxypsoralen(8-MOP), 5-methoxypsoralen(5-MOP) and 4, 5, 8-trimethylpsoralen (TMP) are the phototoxic drugs used in photochemotherapeutic treatment and comparative studies between these three drugs for pigment deposition have been rarely made. In this study,116 mature black male mice of C-57 BL strain were divided into 9 test groups and 1 control group, the former were painted with 8-MOP, 5-MOP and TMP in concentrations of 0.02%, 0.1% and 0.5% each and the latter with a basic solution, and UVA was irradiated after 30 minutes. The amounts of UVA exposure were 150mj/cm**2 in the first week, and 200mj/cm**2 in the second week, 250mj/cm**2 in the third week and 300mj/cm**2 from the fourth week on twice weekly for 7 weeks. Skin biopsies were performed at 1, 3, 5 and 7 weeks after UVA irradiation and were stained with split-dopa and the number, area and perimeter of the melanocytes were measured to observe the changes of the cells. The following results were obtained: 1. Comparison of the number of melanocytes After 3 weeks of drug painting, significantly more melanocytes were seen in the THP-painted group than in 5-MOP- and 8-MOP-painted groups(P<0.05). Between the 8-MOP-and 5-MOP-painted groups, the only difference was the appearance of significantly more melanocytes in the 0.l% and 0.5% 5-MOP-painted groups after 5 weeks of painting and also more cells in the 0.l% 8-MOP-painted group after 7 weeks(P<0.05). In a comparative study between the phototoxic drugs at 0.l% concentration, the changes was 5, 7, 3, 1 week in a decreasing order and the comparison between the concentrations after 5 weeks of painting showed changes in a decreasing order of 0.1%, 0.5%, 0.02%. 2. Comparison between the areas of melanocytes The area of the melanocyte was larger in the TMP-painted group than others at a concentiation of 0.5% after 1 and 3 weeks of painting, and at 0.l% and 0.5% after 5 weeks, and at all concentrations after 7 weeks (P<0.05). Between the 8-MOP-painted group and 5-MOP-painted group, there were no differences except there were significantly larger melanocytes in 8-MOP-painted group after 1 week of painting, and in the 0.1% 8-MOP-painted group after 7 weeks and larger cells were observed in 0.1% 5-MOP-painted-group after 5 weeks (P<0.05). In a comparative study between the phototoxic drugs at 0.1% concentration, the changes was 5, 3, 7, 1 week in a decreasing order and the comparison between the concentrations after 5 weeks of painting showed changes in a decreasing order of O.1%, 0.5%, 0.02%. 3. Comparison between the perimeter of melanocytes The perimeter of melanocytes was longer in the TMP-painted group than others at all the concentrations after 3 weeks of painting and in the 0.02% and 0.5% groups after 5 weeks (P<0.05). However, an unexpectedly lower value was obtained in the 0.1% group after 1 week of painting (P<0.05), There were no differences between 8-MOP-painted group and 5-MOP-painted group except that the perimeter of melanocytes was significantly longer in the 0.5% 8-MOP-painted group after 1 week of painting and in the 0.1% and 0.5% groups after 7 weeks and was longer in the 0.l% 5-MOP-painted-group after 5 weeks(P<0.05). In a comparative study between the phototoxic drugs at 0.1% concentration, the changes was 5,3,7,1 week in decreasing order and the comparison between the concentrations after 5 weeks of painting showed changes in a decreasing order of 0.1%, 0.5%, 0.02%. The results of measuring the number, area, and perimeter of the melanocytes after painting and ultraviolet radiation were higher in the TMP-painted group than in the 8-MOP or 5-MOP painted groups, and there were no differences between the 8-MOP and 5-MOP painted groups. The weekly changes showed an increasing value until 5 weeks, and after that showed a decrease. In comparison of the drug concentrations used,0.1% produced the same or higher values than 0.5%. Few studies have been done on 5-MOP in photochemotherapy, but in this study, it produced a similar pigment-producing effect as 8-MOP. Therefore, we think that it is a drug worth studying to a greater degree in the future.restrictio

(The) effect of herpesvirus infection on the expression of cell adhesion molecules on the cultured human

의학과/박사[한글] 단순포진 바이러스(Heroes simplex virus: HSV)는 안면-구강 단순포진, 음부 포진 및 포진성 각막염 등의 원인균이며 HSV에 대한 세포매개면역이 포진성 각막염, 다형홍반, 베체트병 등의 유발에 중요한 역할을 할 것으로 시사되어 왔다. 또한 이들 질환들의 유발과정에 혈관 내피세포의 변화가 중요한 역할을 할 것으로 생각되고 있다. 염증 반응에서 순환하는 림프구가 혈관 내로부터 염증 반응이 일어나고 있는 주변 조직으로 이동하려면 첫단계로 반드시 혈관 내피세포에 부착한 다음 유주하여야 하며, 혈관 내피세포에 대한 림프구의 유착은 혈관 내피세포 표면에 발현되는 세포유착분자에 의해 중개되는데 이 과정은 여러 싸이토카인에 의해 조절될 수 있다. 본 연구에서 혜르페스 감염에 의해 혈관 내피세포 표면 세포유착분자 발현과 림프구 유착도가 조절될 수 있는지를 알아보고자 배양한 인체 진피 미세혈관 내피세포(human dermal micro-vascular endothelial cell: HDMEC)에 헤르페스 바이러스를 감염시킨 후 면역형광 유량 세포분석법 및 효소면역표지법을 이용하여 혈관 내피세포 표면 intercellular cell adhesion molecule 1(ICAM-1), vascular cell adhesion molecule 1(VCAM-1) 및 E-selectin 분자의 발현변화를 관찰하였으며 HDMEC에 대한 T림프구 유착실험을 시행하여 다음과 같은 결과를 얻었다. 1. 배양한 HDMEC에 제1형 HSV(HSV-1) 처치 24시간 후부터 세포변성 효과가 나타났으며 48시간 후까지 지속되었다. 2. 배양한 HDMEC에 HSV-1, 제2형 HSV 및 홍역 바이러스 처치 4시간 후 ICAM-1, VCAM-1 및 E-selectin분자의 발현이 증가하였으나 거대세포 바이러스 및 불활성화시킨 HSV-1을 처치 시에는 ICAM-1, VCAM-1 및 E-selectin분자의 발현변화를 보이지 않았다. 3. HSV-1 감염에 의한 HDMEC 표면 ICAM-1, VCAM-1 및 E-selectin분자의 발현 증가 및 유도는 항 IL-1α 항체와 항 TNF-α 항체 처치에 의해 일부 억제되었다. 4. 배양한 HDMEC에 HSV-1 및 역 바이러스 처치 후 HDMEC에 대한 T림프구의 유착율이 증가하였으며 거대세포 바이러스 처치 후에는 유착율에 변화를 보이지 않았다. 5. HSV-1 처치 16시간 후 HDMEC에 대한 T림프구의 유착도는 항 ICAM-1 항체 처치 후에만 유의하게 억제되었다. 6. HSV-1 처치 16시간 후 HDMEC에 대한 T림프구의 유착도는 항 IL-1α 항체와 항 TNF-α 항체 처치에 의해 유의하게 억제되었다. 7. 배양한 HDMEC에 HSV-1 처치 16시간 후 배양 상청액에서 IL-1α 및 TNF-α가 검출되었다. 이상의 결과로 보아 HSV가 배양한 혈관 내피세포에 작용하여 혈관 내피세포 표면 ICAM-1, VCAM-1 및 E-selectin분자의 발현 증가를 유도하고 주로 ICAM-1분자 발현변화가 혈관 내피세포에 대한 T림프구의 유착을 중개할 것으로 생각되며 이 과정에 HSV에 의해 생성된 IL-1α흑은 TNF-α가 관여할 것으로 사료된다. [영문] The herpes simplex virus(HSV) causes oropharyngeal herpes simplex, genital herpes and keratoconjuntivitis. Cell-mediated immune response to HSV may be important in the pathogenesis of various inflammatory diseases such as herpes keratitis, erythema multiforme or Behcet's disease. The migration of leukocytes from the circulation into the tissue sites of inflammation is an essential process in the inflammation, with the adhesion of leukocytes to endothelial cells marking the first step. The binding of T lymphocytes to endothelial cells is governed by the expression of cell adhesion molecules such as ICAM-1, VCAM-1 or E-selectin. To determine whether herpesvirus infection induces the regulation of expression of endothelial cell adhesion molecules on cultured human dermal microvascular endothelial cells(HDMEC) and the regulation of T lymphocytes binding to HDMEC, this study utilized immunofluorescence flow cytometry and the enzyme-linked immunosorbent assay to observe the changes in the expression of adhesion molecules on HDMEC after herpesvirus infection, and the binding assay of T lymphocytes to cultured HDMEC was performed. 1. Following the treatment of HSV-1 on cultured HDMEC, the cytopathic effect was observed after 24 hours of incubation and after 48 hours of incubation. 2. The expression of ICAM-1, VCAM-1 or E-selectin on HDMEC increased significantly after the treatment of HSV-1, HSV-2 or measles virus on HDMEC, but there was no significant change after the treatment of inactivated HSV-1 or cytomegalovirus on HDMEC. 3. Anti-IL-1α antibody or anti-TNF-α antibody partially inhibited the expression of ICAM-1, VCAM-1 or E-selectin on HDMEC. 4. The biniding of T lymphocytes to cultured HDMEC increased significantly after the treatment of HSV-1 or measles virus on HDMEC and was not changed significantly after the treatment of cytomegalovirus. 5. The binding of T lymphocytes to HDMEC was inhibited significantly after 16 hours of incubation following the treatment with anti ICAM-1 antibody to HDMEC. 6. The binding of T lymphocytes to HDMEC was inhibited significantly after 16 hours of incubation following the treatment with anti-IL-1α antibody or anti-TNF-α antibody to HDMEC. 7. IL-1α and TNF-α were observed after 16 hours of incubation following the treatment of HSV-1 on cultured HDMEC. This data suggests that HSV induces the increased expression of ICAM-1, or induction of VCAM-1 and E-selectin on HDMEC, and that among these adhesion molecules, mainly the expression of ICAM-1 on HDMEC regulates the binding of T lymphocytes to HDMEC. The data also suggests that IL-1α or TNF-α which was produced by HSV infection from HDMEC may be related with these events.restrictio