Expression of Toll-like Receptor-2 on the Peripheral Blood Monocytes in Kawasaki Disease Patients

Objective : Toll like receptor(TLR) is known to be involved in innate immunity. Many microbial antigens stimulate TLR, and as a result of intracellular signal transduction, they activate nuclear factor-kB which produces diverse inflammtory cytokines. Until now, many research topics in Kawasaki disease focused on cytokine increasement. In this study, we aim to reveal TLR increasement which might be associated with initiation of inflammatory response. Methods : We obtained the peripheral blood of ten patients who were diagnosed with Kawasaki disease in Yonsei University College of Medicine from March 2003 to August 2003, as well as those of a febrile control group and the same number of a normal control group. Flow cytometry was done in all samples for quantification of TLR-2 expression in CD14 positive monocyte. And we also extracted total RNA of periphral monocyte and quantificated expression of TLR-2 mRNA by RT- PCR. Results : The expression of TLR-2 in Kawasaki disease increased significantly compared with the normal control group but not when compared with the febrile control group. And the expression decreased slightly in the subacute phase of Kawasaki disease compared with the acute phase, but this was statistically insignificant. mRNA expression of TLR-2 in peripheral blood monocyte also increased in the acute phase of Kawasaki disease. Conclusion : Expression of TLR-2 in Kawasaki disease increased when compared with the normal control group, which means that innate immunity is associated with the pathogenesis of Kawasaki disease.ope

Effect of a Flavon Extracted from Artemisia absinthium on Collagen Induced Arthritis in Mice

PURPOSE: In this study, a possible suppressive effect of a flavon extracted from Artemisia absinthium on a mouse collagen-induced arthritis (CIA) model was investigated.0aMETHODS: DBA/1 mice were injected intradermally with emulsified chicken type II collagen. Three weeks after immunization, a flavon was introduced p.o. everyday. Clinical incidences of arthritis and arthritis index were measured. Measurement of anti-collagen antibodies and a stimulation index of the splenocytes of the mice were measured. IL-10 and TNF-alpha in the supernatants of the mice sera were measured by ELISA. mRNA expression for IL-10 and TNF-alpha in the splenocytes were tested.0aRESULTS: Flavon extracted from Artemisia absinthium appears to be an effective suppressor of CIA in mice. The serum anti-collagen antibody level and stimulation index of the cultured splenocytes showed no significant differences among the three experimental groups. Also serum IL-10 and TNF-alpha levels did not show any significant differences among the three experimental groups. An increased expression of mRNA for IL-10 was observed in the splenocytes treated with flavon.0aCONCLUSION: With these results, flavon extracted from Artemisia absinthium appears to have a suppressive effect of CIA. The mechanism of the suppressive effect of flavon extracted from Artemisia absinthium may be from a stimulation of IL-10 production.ope

Statistical Analysis of 1,000 Cases of Kawasaki Disease Patients Diagnosed at a Single Institute

Purpose : To find the risk factors associated with coronory artery lesions, non-responsiveness to intravenous immunoglobulin(IVIG) treatment, and recurrences in Kawasaki disease patients. Methods : We retrospectively analyzed 1,000 Kawasaki disease patients who were admitted to Yonsei University Medical Center from September 1990 to December 2003. We compared between responder and non-responder groups to IVIG treatment as well as between relapsed and non-relapsed groups, and as to the relapsed group, we also compared variables between patients in their first and second attack states. Finally, factors associated with longer-fever duration from disease onset were evaluated. Results : Longer fever durations before and after IVIG treatment, male sex, lower Hgb and Hct level, higher WBC count and segmented WBC proportion, and higher CRP and Harada's score were related with coronary artery lesions. Non-responsiveness was related to higher WBC count, segmented WBC proportion, CRP, SGPT, Harada's score, and pyuria. Moderate-to-severe coronary artery dilatations and recurrences were more commonly seen among the non-responder group. No significant predictive factors for recurrence were found. In the relapsed group, lower WBC count, CRP, and shorter fever duration from disease onset were observed in their second attack state. Fever duration from disease onset showed positive correlation with WBC count, CRP, and Harada's score and negative correlation with Hgb levels. Conclusion : Higher WBC count, CRP, and higher Harada's score were related to both higher incidences of coronary artery lesions and non-responsiveness to IVIG treatment, and these factors were also related with longer fever duration. Non-responders to IVIG treatment showed higher recurrence rate and more moderate-to-severe coronary artery dilatations than responders.ope

A Clinical Study of Infective Endocarditis in Childhood

Purpose : Advances in the treatment of congenital heart disease and a decline in the incidence of rheumatic fever has led to changes in the causative organisms and the clinical outcome of infective endocarditis(IE). We sought to analyze the clinical outcome, prognostic factors, causative organisms and corresponding antibiotic sensitivity in IE. Methods : Retrospective analysis of medical records of 104 children diagnosed and treated with IE at Severance Hospital, Yonsei University College of Medicine from January 1986 to June 2003 was undertaken. According to the Duke criteria, 55 patients were classified into the definite group(DG) and possible group(PG). Results : Thirty one cases(56.4%) fulfilled the criteria for the definite group in the Duke criteria, whereas 24 cases(43.6%) fulfilled the criteria for the possible group. The most common chief complaint on admission was fever(93%). The most common infecting organism was Staphylococcus aureus, which was found in 14 cases(48.3%). Three cases(21.4%) of this organism were methicillin- resistant S. aureus(MRSA). Other causative organisms were α-streptococcus(seven cases, 24.1%), Staphylococcus epidermidis(three cases, 10.3%), Citrobacter freundii(one case, 3.8%), Enterococcus faecium(one case, 3.4%) and Candida albicans(three cases, 10.3%). Penicillin-resistant organisms were found in 90.5%(19/21) of total cases and the most sensitive antibiotics were vancomycin(13/13, 100 %) and teicoplanin(12/12, 100%). One case of IE due to MRSA unresponsive to vancomycin was treated with Arbekacin. Conclusion : The incidence of IE caused by S. aureus, especially MRSA, is increasing. Multi-drug resistant organisms are also emerging as a frequent cause of IE. Thus, in patients strongly suspected of having IE in patients with underlying heart disease, glycopeptides such as vancomycin combined with aminoglycosides should be considered, and if fever and positive blood cultures continue despite treatment with glycopeptides, a consideration of the use of new antibiotics may improve the treatment results.ope

로듐 촉매에 의한 알카인의 비대칭 고리화 반응

학위논문 (박사)-- 서울대학교 대학원 : 자연과학대학 화학부, 2019. 2. 이철범.본 학위 논문에는 로듐 촉매에 의한 비대칭 고리화 반응의 개발에 대한 연구 결과가 수록되어 있다. 고리화 반응을 위한 전 이금속-바이닐리딘 매개 촉매 반응의 활용 가능성을 확장시키기 위하여(제 1 장), 말단 알카인에 연결된 엔아민에서 일어나는 로듐 촉매 알켄화 반응에 대한 연구를 수행하였다(제 2 장). 로듐-바이 닐리딘 착물을 촉매 중간체로 활용하여 알카인-엔아민의 고리화 반응을 수행하고, 궁극적으로 카이랄 엔아민을 사용한 부분 입체 선택적 탄소-탄소 결합 형성 반응을 통해 카이랄 사차 탄소를 지 닌 사이클로펜텐 합성법을 제안한다. 본 논문의 후반부는 로듐 촉매와 유기붕소산에 의한 알카 인의 이웃 자리 탄소기능화 반응의 연구 결과를 다루고 있다(제 3 장). 알카인-이민의 로듐 촉매 연쇄 첨가-고리화 반응에서는 단일 로듐 촉매가 순차적인 분자간, 분자내 1,2-탄소로듐화 반응을 매개 하여 알킬리덴-사이클로뷰틸아민의 합성을 가능토록 한다(제 4 장). 또한 로듐 촉매에 배위할 수 있는 카이랄 리간드에 의한 거울상 선택적 반응을 통해 높은 광학 활성을 갖는 사이클로뷰틸아민의 합성법을 보인다. 앞서 확인한 알켄-로듐 중간체의 탄소-질소 이중 결합 첨가 반응성을 바탕으로 알카인-하이드라존의 로듐 촉매 연 쇄 첨가-고리화-재배열 반응을 개발하였다(제 5 장). 본 연구에서는 로듐-촉매 연쇄 고리화 반응과 레트로-엔 반응의 융합을 통해 무흔적 사이클로알켄 합성을 수행하고, 반응 중간체를 분석하여 반응 메커니즘을 규명한다. 로듐-카이랄 리간드 착물은 알켄-로듐 중간 체의 비대칭 탄소-질소 이중 결합 첨가 반응을 유도하고, 결과적으 로 분자 밖 입체 중심을 지닌 사이클로펜틴을 높은 거울상 순도로 합성한다.Described here is the development of rhodium-catalyzed asymmetric cyclization reactions of alkynes. For the amplification of synthetic utilities of transition metal vinylidene mediated catalysis in carbocyclization reactions (Chapter 1), a rhodium-catalyzed intramolecular alkenylation of enamines tethered with terminal alkyne was developed (Chapter 2). By using a rhodium-vinylidene complex as a catalytic intermediate, 5-endo-dig Conia- ene type process could be achieved with alkynylenamine substrates. Furthermore, chiral enamines derived from chiral primary amines could induce diastereoselectivity in the C‒C bond formation, giving rise to cyclopentenes that have a chiral quaternary carbon. In contrast to the works described above for the anti-Markovnikov carbofunctionalization of terminal alkynes, following studies focused on a rhodium-catalyzed vicinal carbofunctionalization of alkynes with organoboron compounds (Chapter 3). In a rhodium-catalyzed tandem addition‒cyclization of alkynylimines, a single rhodium catalyst mediated a sequential inter- and intramolecular 1,2-carborhodations, providing alkylidene cyclobutylamines (Chapter 4). We have shown that hydrolysis- prone aliphatic sulfonylimines could participate in a tandem process, and the exploration of chiral diene ligands enabled the asymmetric induction making chiral cyclobutylamine with excellent enantioselectivity. With the feasibility of catalytic alkenyl addition to the C=N bond, the scope of the C=N bond was expanded by using sulfonylhydrazones instead of imines (Chapter 5). Under mild and operationally simple reaction conditions, traceless endocyclic alkene synthesis could be achieved based on the merger of rhodium-catalysis and pericyclic rearrangement. Mechanistically, alkynylhydrazones gave cyclic hydrazide intermediate by the rhodium-catalysis with organoboronic acids, and it was decomposed to the product via allylic diazene with the extrusion of dinitrogen gas. Furthermore, chiral diene ligands could induce enantioselective addition of the alkenyl rhodium intermediate to the C=N bond, affording an enantioenriched C‒N stereocenter whose chirality is transferred to an allylic position via stereospecific rearrangement.Chapter 1. Transition Metal Vinylidene Mediated Catalytic Carbocyclization of Alkynes 1.1 Introduction 19 1.2 Carbocyclization by nucleophilic addition 1.2.1 Enol and enamine nucleophiles 19 1.2.2 Alkene and alkyne nucleophiles 21 1.2.3 Carbocyclization initiated by oxygen nucleophiles 25 1.3 Carbocyclization by pericyclic reaction 1.3.1 Electrocyclization 29 1.3.2 Cycloaddition 31 1.3.3 Sigmatropic rearrangement 34 1.4 Carbocyclization with disubstituted metal vinylidenes 36 1.5 Conclusion 45 1.6 Reference 47 Chapter 2. Rhodium-Catalyzed Carbocyclization of Alkynylenamines 2.1 Introduction 50 2.2 Results and discussion 2.2.1 Carbocyclization of N-benzyl alkynylenamine 55 2.2.2 Substrate scope 58 2.2.3 Asymmetric carbocyclization of alkynylenamines 60 2.2.4 Proposed mechanism and mechanistic studies 63 2.2.5 Dual catalysis: Merging rhodium-catalysis with organocatalysis 70 2.3 Conclusion and future studies 80 2.4 Reference 83 2.5 Experimental section 2.5.1 General remarks 85 2.5.2 Synthesis and characterization for compounds 2.5.2.1 General procedure for alkylation of β-ketoesters 85 2.5.2.2 General procedure for the alkynylenamines 88 2.5.2.3 General procedure for the rhodium-catalyzed carbocyclization of alkynylenamines 93 2.5.3 Determination of the enantiomeric excess 96 Chapter 3. Rhodium-Catalyzed Tandem Addition– Cyclization Reactions of Alkynes with Organoborons 3.1 Introduction 99 3.2 Tandem addition‒cyclization with unsaturated carbon‒heteroatom bonds 100 3.3 Tandem addition‒cyclization with unsaturated carbon‒carbon bonds 105 3.4 Conclusion 113 3.5 Reference 114 Chapter 4. Rhodium-Catalyzed Tandem Addition– Cyclization of Alkynylimines 4.1 Introduction 116 4.2 Results and discussion 4.2.1 Substrate scope 120 4.2.2 Asymmetric carbocyclization of alkynylimine 123 4.3 Conclusion 126 4.4 Reference 127 4.5 Experimental section 4.5.1 General remarks 128 4.5.2 Synthesis and characterization for substrates 128 4.5.3 General procedure for the rhodium-catalyzed tandem cyclization 131 4.5.4 Characterization for products 132 4.5.5 Procedure for enantioselective rhodium-catalyzed tandem cyclization 138 4.5.6 Preparation of the rhodium-diene complex 4.25 138 Chapter 5. Rhodium-Catalyzed Tandem Addition– Cyclization–Rearrangement of Alkynylhydrazones 5.1 Introduction 139 5.2 Results and discussion 5.2.1 Preliminary results 146 5.2.2 Optimization of reaction conditions 150 5.2.3 Substrate scope of organoboronic acids 153 5.2.4 Substrate scope of alkynylhydrazones 157 5.2.5 Arylative ring contraction of cyclohexenones 170 5.2.6 Competition experiments with alkynylaldehyde 173 5.2.7 Asymmetric carbocyclization of alkynylhydrazones 175 5.2.8 Mechanistic studies 182 5.3 Conclusion 186 5.4 Reference 187 5.5 Experimental section 5.5.1 General remarks 190 5.5.2 Synthesis and characterization for substrates 191 5.5.3 General procedure for the rhodium-catalyzed tandem reaction 215 5.5.4 Characterization for products 216 5.5.5 Competition experiments with alkynylaldehyde 246 5.5.6 Determination of the absolute stereochemistry of 5.35 247 5.5.7 Mechanistic studies 249Docto

Serotype and antimicrobial susceptibility of streptococcus pneumoniae

의학과/석사[한글]폐구균은 비인두의 상재균이면서, 소아에서 급성 중이염, 지역사회 획득 폐렴의 가장 흔한 원인이며, 침습성 세균 감염 질환의 가장 흔한 원인 균주이다. 중이염, 폐렴 등의 국소 감염 뿐 아니라 균혈증, 복막염 및 뇌수막염 등의 침습성 질환 등 다양한 질환을 일으킨다. 현재까지 90개의 혈청형이 알려져 있는데, 시대와 지역에 따라 혈청형 분포의 차이를 보인다. 항생제의 지속적 개발과 치료에도 불구하고 폐구균에 의한 균혈증은 아직까지도 높은 사망률을 보이고 있으며, 특히 항생제 내성의 증가로 치료에 어려움이 더하고 있다. 현재 7개의 혈청형을 포함하는 7가 폐구균 단백 결합 백신이 사용 중인데, 그 효용성을 정확히 판단하기 위해서는 각 지역의 폐구균 혈청형 분포에 대한 연구가 필수적이다.본 저자는 2001년 9월부터 2005년 7월까지 신촌세브란스 병원에 내원하여 배양 검사 상 폐구균 감염이 확진된 308명의 환자로부터 분리된 폐구균의 혈청형 분석과 항생제 감수성 조사를 시행하였다.폐구균은 객담(62.3%)에서 분리된 경우가 가장 많았고, 혈액(13.0%), 이루(11.0%), 인두(3.9%) 등의 순이었다. 265주에서 혈청형 분석이 가능하였는데, 19F(16.2%), 19A(12.8%), 23F(8.7%), 6B(7.9%), 6A(7.2%) 및 3(6.0%)의 순으로 나타났다. 15세 이하 소아에서는 52주에서 혈청형 분석이 시행되었는데, 19F, 19A, 23F, 14, 6B, 6A, 4 및 11A의 순으로 조사되어 전체적 양상과 유사하게 나타났다. 페니실린 내성률은 64.6%였으며, 소아 환자의 경우 67.3%였는데, 2세 이하 소아의 경우 78.1%의 높은 페니실린 내성률을 나타내었다. 이를 혈청형 별로 살펴보면 흔하게 분리되는 균일수록 더 높은 항생제 내성률을 나타내었다. 3종 이상의 항생제에 대해 내성을 보이는 다제 내성 폐구균의 빈도는 64.7%로 나타났다.현재 시행 중인 7가 폐구균 단백 결합 백신에 포함되는 혈청형은 전체의 48.3%였으며, 소아의 경우 61.5%로 나타나, 향후 지속적으로 7가 폐구균 단백 결합 백신을 시행하여야 할 것으로 생각된다. 현재까지 7가 폐구균 단백 결합 백신 도입 이후 뚜렷한 혈청형 분포의 변화는 관찰되지 않는 상태이다. 그러나 외국의 경우 7가 폐구균 단백 결합 백신 도입 이후 일부 혈청형 분포의 변화가 관찰되고 있어, 우리나라에서도 향후 이에 대한 지속적인 조사가 필요할 것으로 생각된다. [영문]Pneumococcus is the most common cause of acute otitis media, community acquired pneumonia and invasive bacterial diseases such as sepsis, peritonitis and meningitis in children. Ninety serotypes have been identified and the distribution differs according to geographic area and ages. Pneumococcal sepsis causes a high mortality rate despite the development of new antibiotics from the emergence of antibiotic resistant strains. The 7 valent pneumococcal conjugate vaccine is used widely. To evaluate the efficacy of the vaccine, it is essential to investigate the distribution of the pneumococcal serotypes.The serotypes and antibiotic resistance of the pneumococcus isolated from 308 patients at Shinchon Severance hospital from September of 2001 to July of 2005 were analyzed.The pneumococcus were isolated mostly from sputum and blood, ear discharge, pharynx in the descending order.Serotyping was possible in 265 cases and the distribution of serotypes were 19F(16.2%), 19A(12.8%), 23F(8.7%), 6B(7.9%), 6A(7.2%) and 3(6.0%). Fifty two cases were isolated from those patients less than 16 years of age and the distribution of serotypes was 19F, 19A, 23F, 14, 6B, 6A, 4 and 11A which was similar to the total distribution. Resistance to penicillin was 64.6% in all cases and 67.3% in children. The highest rate of penicillin resistance was 78.1% in those less than 2 years of age. The more common serotype showed the higher rate of penicillin resistance. Multi-drug resistance, resistant to 3 or more antibiotics was demonstrated in 64.7% of the samples. Forty three percent of the total identified serotypes were included in the 7 valent pneumococcal conjugate vaccine. And 61.5% of the serotypes identified in children were included in the vaccine. The pneumococcal conjugate vaccine should be recommended. A serotype switch after the use of the protein conjugated vaccine, which has been reported in other countries, has not been demonstrated in Korea yet. Further study is needed to address this issue.ope

진단 및 면역치료 시약 개발을 위한 모기 침샘 내 항원에 대한 생쥐의 체액성 면역 반응

Dept. of Medicine/박사The mouthparts of mosquito are modified to pierce the tissues and suck blood from humans or other mammals. Their bites can cause immediate cutaneous reactions, such as wheal and flare, delayed reactions and occasionally systemic reactions in humans. IgE-mediated allergic reactions caused by mosquito bites are a common problem all over the world. This study was undertaken to determine IgE levels in anti-mouse serum, to elucidate mouse IgE binding patterns and to investigate the immunogenicity of salivary gland antigens of Aedes togoi. Mosquito larvae of Aedes togoi were collected and maintained in the laboratory. The mosquito specific mouse IgE level was measured using ELISA. Polypeptide patterns were analyzed by SDS-PAGE. Western blot was performed with sensitized immune mouse sera, and elucidated mouse IgE binding patterns to salivary gland extracts. Protein band patterns of the salivary gland extracts (SGE) and whole body extracts (WBE) of the specimens were different from one another. Specific mouse IgE reacted to the protein in SGE of 18.0, 33.0, 35.0, 37.0, 45.0, 57.5, 72.0, 90.0 and 150.0 kDa from Aedes togoi. Molecular biological techniques were used to study the genetic information and functions of genes. The cDNA sequencing was carried out to elucidate and compare the genome of Aedes togoi with other coded gene of the allergen. Two previously unknown protein coding genes(DUF 1398, DUF 2528) were identified among the 45 positive clones prepared from the mosquito salivary gland by immunoscreening. Analysis of the 3D structure of DUF1398 and DUF2528 was not similar with any other allergens identified in plants or animals, despite low sequence identities to their templates, the global folds of the 3D models of the cockroach allergen Bla g 4 and the mosquito salivary protein antigen Aed a 2 had a sizable fraction of structural overlap, suggesting that it would be a potential target for therapeutic agents in specific mosquitoes bite allergens.ope

Mining ‘Followees’ in a Mobile Network

2

A Case of Mitochondrial Respiratory Chain Defect Diagnosed in the Neonatal Period

Mitochondrial diseases are classified into the three major categories, defects of fatly acid oxidation, defects of pyruvate metabolism, and defects of the respiratory chain, and all of these cause severe neuron-logic dysfunction in the newborn period. Defects of the mitochondrial respiratory chain present as recurrent apnea, seizures, congenital lactic acidosis, hypotonia, hepatic dysfunction and hypertrophic cardiomyopathy in the neonatal period. Laboratory findings of hyperlactataemia (>2.5mM), elevated lactate/ pyruvate (L/P) ratio (>20) and ketone body ratio (>2) suggest the diagnosis of mitochondrial respiratory chain defects. We report a case of mitochondrial respiratory chain defect diagnosed in the neonatal period presenting with multiorgan failure consisting of severe metabolic acidosis, comatous mental state, respiratory distress, hepatic dysfunction, renal failure with lactic acidosis (24mM), increased L/P ratios (55.6) and ketonuria (increased ratio of 3-hydroxybutyrate/acetoacetate).ope