다양한 변수조절 하에 레이저 용접한 주조 코발트 크롬 합금의 굽힘강도 비교

Thesis(masters) --서울대학교 대학원 :치의과학과 (치과보철학전공),2009.8.Maste

의료기관에 대한 국가결핵관리지침의 개선방안 연구 : 서구 주요국과 비교제도론적 분석을 중심으로

보건대학원/석사In 1993, World Health Organization(WHO) has declared a global health emergency with respect to tuberculosis(TB) problems, but 900 million people are still diagnosed with TB each year. Also, 150 million people have died of TB. South Korea has faced on increasing risk of multidrug-resistant TB and having the disgrace that ranked the top in TB incidence and mortality rate among OECD member countries. The purpose of this study is to realize TB control policies in health-care facilities in South Korea and to suggest the improvement plan by identifying the status through comparing with other western countries: U.S.A., Canada, and U.K. Based on the literature review of the situation of TB infection control in health-care facilities in South Korea, a focus group interview had performed. And then, several experts’ advice were collected for the analysis to prioritize among the results of the comparative methodological study for TB control guideline with the other western countries. The result of the above research is that there are many aspects need to be improved in Korean national tuberculosis policy, compared to the Western’s. Regards TB infection control in health-care facilities, the government''s initiative is expected rather than that of the facilities’. experts generally agreed on the need to strengthen TB infection control in the health-care facilities, but their opinions about the importance and the degree are varied. In conclusion, it is needed to enhance the national TB control system by supplementing the parts that do not exist in the current Korean guidelines in health-care facilities.restrictio

난백알부민에 의해 유도된 식품알레르기의 면역반응에서 활성백혈구부착분자 (ALCAM/CD166)의 역할

Dept. of Medical Science/석사Food allergy is an abnormal immune response resulting from failing to establish oral tolerance and considered one of the worldwide major health problems. Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a member of immunoglobulin superfamily transmembrane glycoproteins and express on surface of antigen presenting cells (APCs), especially dendritic cells (DCs). CD6 is known for co-stimulatory molecule and binds with ALCAM. There are many studies that long term interaction of CD6 and ALCAM affects immune response. However, there are currently no studies identified functions of ALCAM in food allergy. So, this study aimed to identify the functions of ALCAM in OVA-induced food allergy. Female BALB/c wild type (WT) mice and ALCAM mutant (ALCAM-/-) mice were intraperitoneally sensitized and orally fed with ovalbumin (OVA). After last challenge, mice were assessed parameters of experimental food allergy, including clinical and diarrhea scores, and core temperature. Mice were sacrificed and analyzed systemic immune responses such as expression of TH2 cytokines, levels of serum total IgE and OVA-specific IgE, injury score of H&E stained intestine, and T cell responses. Food allergy-induced WT mice showed decreased expression of ALCAM mRNA in small intestine and increased levels of ALCAM in serum. Clinical and diarrhea scores, serum total IgE and OVA-specific IgE levels, mRNA expressions of TH2 cytokines (IL-4, IL-5, IL-13), and injury score of H&E stained small intestine were enhanced in OVA-challenged WT mice against control mice. In contrast, these parameters and immune responses of food allergy were attenuated in OVA-challenged ALCAM-/- mice. T cell proliferation of total cells from spleen and mesenteric lymph node (mLN), and TH2 cytokines levels of splenocytes cultured media were diminished in OVA-challenged ALCAM-/- mice. Furthermore, proportion of CD3+CD4+ T cell population and activated T cell of spleen, mLN, small intestine were dropped in OVA-challenged ALCAM-/- mice. Lastly, levels of serum ALCAM increased in children with food allergy against healthy control subjects. In conclusion, this study suggests that ALCAM affects immune response in experimental food allergy. That is, ALCAM regulates allergic disease and affects immune responses by alternation of T cell activation and TH2 response in OVA-induced food allergy. 식품알레르기는 경구 면역관용에 실패함으로써 나타나는 비정상적인 면역반응으로, 전세계적으로 주요하게 다뤄지는 건강 문제 중 하나의 질병으로 손꼽힌다. 활성백혈구부착분자 (ALCAM/CD166)는 면역글로불린상과 (IgSF) 에 속하는 막관통 당단백질로, T 세포의 표면에 존재하는 CD6와 상호작용하여 면역반응에서 역할을 하는 것으로 알려져 있다. 또한 ALCAM은 여러 가지 기관에서 발병되는 암의 발생에서 역할을 한다고 알려져 있다. 그러나, 현재 이러한 ALCAM이 알레르기 질병의 면역반응에 미치는 영향이나 기능을 확인한 논문은 없는 것으로 알려져 있다. 따라서 본 연구는 알레르기 질병 중 하나인 식품알레르기 모델에서 ALCAM의 기능을 확인하기 위하여 진행되었다. BALB/c 야생형 마우스와 ALCAM 결핍 마우스에 난백알부민을 복강주사하여 감작시키고 경구투여했다. 그 후 마우스에서 증상에 대한 정도, 체온, 소장의 형태, 혈청 면역글로불린 E, TH2 면역 반응 등을 포함한 식품알레르기 모델의 척도를 확인했다. 식품알레르기를 유발한 야생형 마우스의 소장에서는 ALCAM의 발현량이 감소하였고 혈청에 존재하는 ALCAM의 양은 증가한다는 것을 확인했다. 또한 대조군 보다 난백알부민으로 식품알레르기를 유발한 야생형 마우스에서 증상에 대한 정도, 혈청에 존재하는 총 면역글로불린 E와 난백알부민에 특이적인 면역글로불린 E의 양, TH2 사이토카인 (인터류킨-4, 인터류킨-5, 인터류킨-13)의 발현량, 헤마톡실린&에오신 염색을 한 소장의 손상 정도 등이 증가한 것을 확인하였다. 그에 반해서, 이러한 식품알레르기에 대한 척도가 ALCAM 결핍 마우스에서 억제되어 나타나는 것을 확인했다. T 세포의 보조자극신호 분자로 알려진 CD6가 그의 리간드인 ALCAM에 어떠한 영향을 미치는 지 알아보기 위해 마우스의 비장과 림프절에서 T 세포의 급증을 확인하였을 때, 식품알레르기가 일어난 야생형 마우스보다 ALCAM 결핍 마우스에서 더 감소하는 현상을 확인하였다. ALCAM이 관여하는 T 세포의 변화를 좀 더 특이적으로 확인하기 위하여 마우스의 비장과 림프절, 소장에서 세포를 분리하고 염색하여 CD3+CD4+ T 세포의 분포와 CD4+CD44highCD62Llow에 해당하는 활성된 T 세포의 수를 유세포분석으로 측정하였다. 그 결과 T 세포의 분포와 활성 정도 역시 ALCAM 결핍   마우스의 비장, 림프절, 소장에서 감소하는 것을 확인했다. 마지막으로, 마우스에서 확인한 결과와 같이 건강한 대조군 보다 식품알레르기 증상을 보이는 환아의 혈청에서도 ALCAM의 양이 증가하는 것을 확인하였다. 결론적으로, 본 연구에서 진행한 실험 결과를 통해 ALCAM이 T 세포의 표면에 존재하는 CD6와 상호작용하여 T 세포의 급증, 분포, 활성 등을 유도하고, TH2 면역반응에 영향을 미침으로서 식품알레르기 모델에 연관되어 있다는 것을 확인하였다.ope

Cost-effectiveness of adalimumab in the treatment of patients with rheumatoid arthritis

보건정책관리학과/석사[한글]연구목적: 류마티스관절염 치료에 사용 되는 종양괴사인자억제제 중 국내에 가장 최근에 도입 된 아달리무맙의 비용-효과 분석을 통해 이 약제를 사용하고자 하는 의료진과 환자에게 정보를 제공하고자 하였다. 연구방법: 우리나라에서 아달리무맙의 사용을 보험급여로 인정해주는 기준과 가장 유사한 환자를 대상으로 실시한 아달리무맙의 임상시험인 ARMADA study를 근거로 비교대상 약제를 메토트렉세이트 단독요법과 아달리무맙, 메토트렉세이트 병용요법으로 설정하고 한 주기를 6개월로 설정하였고 분석기간을 총 8주기로 하였다. 분석관점은 사회적 관점과 환자의 관점으로 하였고 마르코프 모델을 이용하여 분석하였다. 모델은 다른 종양괴사인자억제제인 에타너셉트로의 교체투여를 인정하지 않았을 때(모델A)와 인정했을 때(모델B)로 나누어 설계하였고 효과변수는 8주기 중 ACR20을 기준으로 개선 된 상태로 사는 기간으로하고 비용항목은 직접비와 간접비로 나누어 간접비를 포함했을 때와 포함하지 않았을 때로 나누어 각각 분석하였다. 환자 상태의 개선 여부를 판단하는 기준, 치료의 중단율, 비용의 발생을 종합병원으로 가정했을 때, 개선된 상태에서의 생산성 정도에 따라 민감도 분석을 시행하였다. 연구결과: 사회적 관점에서 분석했을 때 모델A의 ICER 값은 약 2,500 만 원, 모델B의 ICER 값은 약 2,700 만 원으로 나타났으며 생산성 손실을 고려했을 때에는 약 2,100 만 원, 2,300 만 원으로 다소 감소하였다. 환자의 관점에서는 모델A의 ICER 값은 약 750 만 원, 모델B는 약 820 만 원으로 나타났다. 민감도 분석 결과 개선 된 환자가 일반인구 집단의 생산성에 어느 정도 도달하는 지에 가장 크게 영향을 받는 것으로 나타났다. 결론: 우리나라의 의료환경 하에서 아달리무맙과 메토트렉세이트의 병용요법이 비용-효과적인지 판단하기 위해서는 추가적인 연구가 필요할 것으로 사료 된다. [영문]Objective: The aim of this study is to analyze the cost-effectiveness of adalimumab which is introduced into Korea recently and provide the information to medical staffs and patients who want to use this drug. Methods: A cost-effectiveness analysis was performed for total 4 years with setting up the one cycle as 6 months comparing combination therapy of adlaimumab + methotrexate and methotrexate monotherapy based on the ARMADA study which is the clinical trial of adalimubab conducted with the most similar patients to the standard accepted by our government for using adalimumab as a reimbursable product in Korea. The analysis was performed on both social and patients perspectives by using Markov model. It is set up as model A and B, and in the model A, switching to etanercept when patients fail to adalimumab was not permitted but in the model B, switching to etanercept was permitted. The value for the effectiveness is the year of improved status based on ACR20 during 4 years, and the cost is categorized into direct and indirect, and analysis was performed separately for each case whether indirect cost is included or not. The sensitivity analysis is performed under the following assumption: a criterion of improved status, the rate of withdrawal, cost based on general hospitals, productivity of improved status. Results: From the social perspective, in the model A, the ICER(incremental cost-effectiveness ratio) was about KW 25 million per 1 year improved status, and KW 27 million in the model B. When the indirect cost was included, the ICER of model A and B turned out to be a little bit decreased as KW 21 million, KW 23 million respectively. From the patients' perspective, the ICER was KW 7.5 million in the model A, and KW 8.2 million in the model B. In the result of analysis, the ICER was the most sensitively responded to the productivity of improved patients group comparing to productivity of normal population group. Conclusions: Further analysis should be conducted to estimate the cost-effectiveness of combined therapy of adalimumab and methotrexate in Korea.ope

Incorporation of C14-labeled carbohydrate into protein in the Walker 256 tumor

homogenates of tumor, liver, brain and kidney tissues excised from Walker 256 tumor animals were divided to 3 aliquots and incubated with C"-l, CU-2 and C"-3-lactate media respectively. C02 yields from each aliquot of experiment were compared to determine the oxidative pathway of intermedially metabolite of sugar and also incorpora• tion of C"•lactate into tissue protein. Results obtained were as follow. 1) Total C02 production rate of tumor tissue was averaged 10. 2±3. 2uM/hr/gm and those of control tissues were showed 27. 8±7. 2 in the liver, 44.0± 6.8 in the brain and 42.7±55 uM/hr/gm in the kidney tissue respectively. These data impressed general oxidative metabolism in the tumor tissues were inhibited compared with those of control tissues. 2) C02 yields from each carbon of lactate in the tumor and control tissues were compared. C02 yields from C-1 carbon of lactate were always larger than those from C-2 and C-3 carbon of lactates. in every tissues. However this difference in the tumor tissue is remarkable as compared with normal tissues. these data suggested that carboxyl carbon of lactate was easily oxidized into C02 in the tumor tissue as In the normal tissues but further oxidation of C•2 and C-3 carbon of lactate, which Is acetate unit, were remarkably inhibited in the tumor tissue. 3) Incorporation of radioactivities of each carbon of lactate into tissue protein was observed in order to trace the fate of 2 carbon compound which is inhibited further oxidation into C02 in the tumor tissue. Incorporations of radioactivities into protein in the CJI-I-Iactate incubation experiments were always lower than those in C"-2 and C"-3-lactate incubation experiments in tumor and control tissues but remarkable difference was observed in the tumor tissue as comparing with control tissue. Thus means remaining 2 carbon compound after decarboxylation of lactate were participate to protein synthesis relatively larger part in the tumor tissues than in the control tissues From the above data we suggested metabolic pathway of lactate in the tumor tissue as in the figure 1

The role of interleukin-17 in mouse models of atopic dermatitis and contact dermatitis

BACKGROUND: Atopic dermatitis (AD) and contact dermatitis (CD) are both T cell-mediated eczematous disorders. Interleukin (IL)-17, expressed by T helper (Th)17 cells, is involved in recruitment of inflammatory cells into AD and CD skin. AIM: In this study, we investigated whether IL-17 regulates immune dysregulation and affects skin barrier in oxazolone (OXA)-induced AD-like and CD-like disease models in mice, by comparing IL-17 null mutant (IL-17(-/-) ) vs. wild-type (WT) mouse strains in the models. METHODS: IL-17(-/-) and WT Balb/c mice were used for OXA induction of AD-like and CD-like skin diseases. Ear swelling was measured by a micrometer. Skin biopsies were obtained for RNA isolation and histology. Real-time quantitative PCR analysis was performed to quantify mRNA expression of Th2 cytokines. Skin permeability was measured by a vapometer, and structural changes in the skin were evaluated by electron and confocal microscopy. RESULTS: Both OXA-induced AD and CD responses were alleviated in IL-17(-/-) mice relative to WT, as demonstrated by reductions in ear swelling, inflammatory cell infiltration and levels of Th2 cytokines. These endpoints were used to characterize inflammatory dysregulation in both AD and CD models. Skin-barrier dysfunction, measured by increases in transepidermal water loss and dysfunction of lamellar bodies, and reductions in lipid distribution, were seen in both AD and CD in WT mice. In IL-17(-/-) mice, however, these responses were significantly diminished. CONCLUSIONS: The results indicate that the IL-17 gene may play a role in modulating immune dysregulation and affecting skin barrier in OXA-induced AD-like and CD-like skin disease models in the Balb/c mouse.ope