사지 운동성 행위상실증을 주소로 내원한 전두측두엽 치매 환자 1예

A 59-yr-old, right-handed woman developed bilateral clumsiness of the hands and dysarthria 6 months prior to admission. A detailed neurologic evaluation showed limb-kinetic apraxia with frontal lobe dysfunction. Brain MRI showed significant anterior temporal lobar atrophy. Brain PET revealed bilateral decreases in glucose metabolism around the motor cortices and temporal lobes, predominantly on the right side. This case suggests that limb-kinetic apraxia is a presenting symptom of frontotemporal dementia

放送委員會의 位相 강화를 위한 議題設定 및 意思決定 過程 硏究 : Kingdon의 정책흐름모형에 의한 연구

학위논문(석사)--서울대학교 대학원 :행정학과 행정학전공,2002.Maste

Fabrication and characterization of large area Hg0.7Cd0.3TeHg_{0.7}Cd_{0.3}Te photovoltaic infrared detector

학위논문(석사) - 한국과학기술원 : 전기 및 전자공학과, 1991.2, [ [iii], 63 p. ]한국과학기술원 : 전기 및 전자공학과

양전하를 띠는 양자점 및 업컨버젼 나노입자를 이용한 생물학적 이미징을 위한 탐침제 개발

Nanoparticles (NPs) have unique physicochemical properties due to the quantum confinement effect. Semiconductor quantum dots (QDs) or upconversion nanoparticles (UCNPs) exhibit interesting properties such as high photoluminescence, photostability, dual magnetic/optical modality. In this study, biocompatible and stable NPs were developed through the various surface modifications. NPs were functionalized by its conjugation with various molecules including antibody for detection of kappa opioid receptor, small peptide for detection of integrin ανβ3 and oligonucleotides for the detection of influenza virus. These functionalized NPs were useful to visualize the endocytosis of kappa opioid receptor in live cell, to acquire in vivo imaging of tumor expressing integrin ανβ3 in mice, and to detect sequence-specific oligonucleotides. These results show the potential of these nanoprobes to apply for the drug screening and in vivo multiplex imaging.Quantum dot 혹은 upconversion nanoparticle과 같은 나노물질들은 그들의 고유한 물리 화학적 특성 (광안정성, 높은 양자수율, 입자크기 조절에 따른 형광파장의 변화, 광학-자기적 특성 등)으로 인해, 생물학 분야에서 기존에 사용되고 있던 유기 형광체를 대체할 물질로 각광받고 있다. 본 연구에서는 다양한 표면개질을 통해 친수화시킨 나노입자를 이용하여, kappa opioid receptor를 표적으로 한 항체, integrin ανβ3 targeting을 위한 peptide 및 influenza virus 검출을 위한 DNA 등과 같은 다양한 biomolecule을 결합시킨 후, 이를 이용하여 살아있는 세포에서 kappa opioid receptor의 endocytosis 과정을 시각화, 동물모델에서 integrin ανβ3 를 발현하는 tumor의 이미징, .혹은 sequence-specific 표적 DNA의 검출 가능성을 보여주었다. 이 결과들을 통해 신약 개발에 필요한 screening 분야로의 응용 가능성과 in vivo multiplex imaging을 위한 탐침제로써의 활용 가능성을 보여주었다.ABSTRACT ⅰ TABLE OF CONTENTS ⅱ LIST OF FIGURES ⅴ LIST OF TABLES ⅸ Ⅰ. INTRODUCTION 1 A. Surface modification of Quantum Dots (QDs) 2 1. Pegylated amine functionalized QD 3 2. QD-DNA sensor based on FRET 3 B. Application of QD for the target protein detection 5 1. QD labeled kappa opioid receptor and drug induced endocytosis 5 2. Application of nanoprobes to drug screening method 7 C. Development of multimodal imaging nanoprobe 8 1. Development of nanoprobes for in vivo tumor targeting 8 2. Multi-imaging modality of UCNP 8 Ⅱ. MATERIALS AND METHODS 9 A. MATERIALS 9 1. CdSe/ZnS QDs synthesis and surface modification with various ligands and polymer 9 2. Positively charged QD and oligonucleotide complex as a target DNA sensing material 9 3. Anti-HA antibody conjugated QDs and κ-OR targeting 11 4. Cyclo RGD conjugated UCNP and integrin ανβ3 binding experiment 11 B. METHODS 12 1. Nanoparticle synthesis and surface modification 12 2. Preparation of QD-antibody conjugates and GPCR targeting 17 3. UCNP-cRGD peptide conjugates and in vivo tumor targeting 19 4. General characterization methods 23 Ⅲ. RESULTS 25 A. Nanoparticle synthesis and surface modification 25 1. Synthesis of CdSe/ZnS QDs and polymer coating 25 2. Characterization of DEDEA ligand exchanged QD and pegylation 26 3. Complex formation of cationic QD with single-stranded oligonucleotides 31 4. Preparation of FRET-based QD-DNA probes 34 5. FRET efficiency of the QD-DNA complexes 35 6. Detection of target oligonucleotides 36 B. Nanoparticles functionalized with biomolecules for in vitro protein imaging 39 1. Amine functionalization of QD 39 2. Preparation of QD-anti-HA antibody conjugates 40 3. Specific binding of QD-anti-HA antibody conjugates to κ-OR 42 4. Endocytosis of QD labeled κ-opioid receptor by agonist 43 5. Real time tracking of κ-opioid receptor internalization 44 6. Endocytosis of κ-OR dependent on its specific agonist 45 7. Endocytosis pathway of κ-OR 46 8. The concentration-dependent effect of κ-OR agonist is visualized using QD-anti-HA antibody conjugates 47 C. Nanomaterials for deep tissue and in vivo imaging study 48 1. Cyclo RGD peptide-conjugated UCNPs 48 2. UCNP-(cRGD)2 bound to U87MG cells highly expressing integrin ανβ3 49 3. T1 weighted MR/micro PET images of mouse bearing U87MG glioma 51 4. Visualization of UCNP in tumor tissue 55 Ⅳ. DISCUSSION 57 A. Pegylated DEDEA-QD and application to production of the QD-DNA probe 57 B. QD-antibody conjugates for κ-ORs targeting and application to drug screening method 58 C. Synthesis of UCNP-(cRGD)2 conjugates and in vivo tumor imaging 59 Ⅴ. CONCLUSION 61 REFERENCES 63 국문요약 72Docto

파킨슨병의 심장자율신경계와 혈관 내피기능의 역할

Cardiac autonomic function, assessed using heart rate variability (HRV) and cardiac iodine- 123-meta-iodobenzylguanidine (MIBG), is altered in Parkinson’s disease (PD) patients. In addition, vascular endothelial function, as measured by flow-mediated dilation (FMD), might play a role in the pathogenesis and progression of neurodegenerative disease. However, little is known about whether cardiac autonomic function might be used in the early diagnosis of Parkinson’s disease (PD), and the extent to which such alterations contribute to the neurodegenerative process is unclear. Further, the involvement of vascular endothelial function in PD remains to be clarified. The clinical significance of cardiac autonomic function in the diagnosis and prognosis of PD and the involvement of vascular endothelial function were investigated in this study. HRV was significantly lower in early PD. Higher HRV was associated with better cognitive function. A reduction in cardiac MIBG uptake was associated with subsequent increased risk of dementia. In addition, FMD was significantly lower in PD patients, and was negatively associated with levodopa treatment. Surgical deep brain stimulation reduced levodopa administration and improved motor disability and FMD. In conclusion, cardiac autonomic dysfunction occurs early in PD and is associated with subsequent risk of developing PD-associated dementia. Vascular endothelial function is also altered in PD and appears to be affected by chronic levodopa treatment.파킨슨병 환자에서는 심장 자율신경계의 이상 (심박 변이도, 심장 신티그래피)이 흔히 관찰된다. 또한 신경퇴행성 질환에서 혈관 내피 기능이 병의 발병 기전이나 진행에 영향을 준다는 보고가 되고 있다. 하지만 초기 파킨슨병에서 심장자율신경계나 혈관 내피기능의 이상이 얼마나 감소되어 있는지, 또한 병의 진행에 어떠한 영향을 끼치는지는 잘 알려져 있지 않다. 따라서 본 연구에서는 심장 자율 신경계나 혈관 내피기능애 대한 임상적 의의 (진단 및 예후) 와 가능한 기전을 조사하였다. 그 결과, 심박 변이도가 초기 파킨슨병에서 현저히 감소되어 있어 조기 감별 진단에 유용하며, 파킨슨병의 렘 수면 장애와 인지기능 저하와 연관성이 있었다. 또한 심장 신티그라피는 파킨슨 환자가 치매로의 전환 위험도를 예측할 수 있었다. 초기 파킨슨병에서 혈관 내피기능은 떨어져 있었으며, 이것은 파킨슨병의 대표적인 약물 치료제인 레보도파와 관련이 있었다. 또한 파킨슨병의 뇌 심부 자극술 수술적 치료 후 레보도파를 현저히 줄인 후 운동기능의 개선과 함께 혈관 내피기능의 상승이 있었다. 결론적으로, 파킨슨 환자에서 심장 자율 신경계의 이상은 초기부터 관찰되고 있으며, 이는 병의 조기진단 뿐 아니라 인지기능과 추후 치매로의 위험도와 연관 있음을 보여주었다. 혈관 내피기능 또한 파킨슨병 초기에서부터 보이고 있으며, 레보도파 약물치료와 관련이 있고 수술적 치료로 약물을 줄인다면 호전될 수 있음을 보여주었다.Abstract i Table of contents ii List of Figures iv List of Tables v Abbreviation vi I. INTRODUCTION 1 1.1. Classical pathogenesis of PD 1 1.2. New Concept of Neurovascular networks in PD 1 1.3. Cardiovascular autonomic system 1 1.4. Vascular endothelial system 2 1.5. Aim of the study 3 II. Materials and Method 4 2.1. Patients 4 2.2. Heart rate variability (HRV) 4 2.3. Cardiac iodine- 123-meta-iodobenzylguanidine (MIBG) 5 2.4. Flow mediated dilation (FMD) 5 2.5. Statistical analysis 6 III. Results 7 3.1 Heart rate variability to differentiate PD from essential tremor (ET) 7 3.2 Heart rate variability in PD with and without REM sleep behavior disorder 11 3.3 Cardiac MIBG and risk of dementia PD 14 3.4. Effect of heart rate variability on cognition in PD 20 3.5. Flow-mediated dilation in PD 22 3.6. Endothelial dysfunction and hyperhomocysteinemia in PD 24 3.7. Effect of levodopa on FMD in PD: Serial follow up study 29 3.8. Effect of FMD on cognition in PD 31 3.9. Effect of deep brain stimulation (DBS) on FMD and HRV 33 IV. Discussion 36 V. Conclusion 39 References 41 국문요약 48Docto

아토피 척수염: 한국에서의 척수염의 새로운 원인

BACKGROUND: HyperIgEemia and atopy has recently been reported to be related with various neurological diseases such as Hirayama disease and idiopathic myelitis. We aimed to determine frequency of atophy or hyperIgEemia in idiopathic myelitis in Korea and to characterize the clinic-laboratory and MRI profiles of atopic myelitis (AM) in comparison with non-AM. METHODS: From 2006 January to 2008 August, twenty nine consecutive patients with idiopathic myelitis (14 AM and 15 non-AM) were enrolled from registry. The frequency of hyperIgEemia and two mite antigen-specific IgE positivity was examined in idiopathic myelitis patients. In addition, we compared clinical data, laboratory results including neuromyelitis optica (NMO)-IgG, autoantibodies, and radiologic findings between AM and non-AM patients. RESULTS: Allergic or atopic history was found in only 4 patients (13%), but hyperIgEemia and mite antigen-specific IgE were observed in 17 (58%) and 19 (65%) of idiopathic myeltis patients, respectively. Patients with AM (n=14, 48%) showed following distinctive features. (1) younger age at onset (39 years vs. 51 years; p<0.0001), (2) non-acute onset (13/14 vs. 5/15; p=0.002) and long-duration of symptom at admission (76 days vs. 16 days; p<0.001), (3) predominant sensory symptom with mild weakness (4) low EDSS score (2.1 vs. 5.6; p<0.001), (5) low frequency of abnormal SEP findings (2/14 vs. 11/15; p<0.005), and (6) increased eosinophils in peripheral blood (5.0% vs. 1.0%; p<0.001). Common MR findings of AM included eccentric lesion occupying more than two thirds of spinal cord (92%) with focal peripheral enhancement (92%) on axial image, and the lesion usually extended more than 3 to 5 vertebral segments (71%) with cord swelling (71%). CONCLUSIONS: HyperIgEemia and mite antigen-specific IgE are fairly common in Korean idiopathic myelitis patients. The AM patients show relatively homogenous clinicolaboratory and radiological features. It is noteworthy that none of these patients shows brain abnormality suggestive of multiple sclerosis or neuromyelitis optica (NMO). These results suggest that AM is a distinct disease entity with different pathogenesis from multiple sclerosis or NMO.서론: 최근에 고IgE혈증과 아토피 질환은 여러 신경계 질환 (히라야마, 홉킨, 원인불명의 척수염)과 관계가 있음이 밝혀지고 있다. 우리는 이번 연구에서 한국에서의 원인 불명의 척수염에서 고IgE혈증과 아토피질환의 빈도를 알아보고, 아토피성 척수염의 임상, 혈청학적 및 방사선학적 특징을 비아토피성 척수염과 비교하고자 한다. 대상 및 방법: 2006년 1월부터 2008년 8월까지 총 29명의 원인 미상의 척수염 환자를 아주대학교 병원 척수염 목록으로부터 확인을 하였다. 우선, 고IgE혈증과 집먼지 진드기에 대한 특이 항체의 빈도를 원인불명의 척수염 환자들에게서 조사를 하였다. 그리고, 아토피 척수염 환자의 임상 양상, 혈청학적 검사와 방사선학적 소견을 조사하였다. 결과: 원인 불명의 척수염 환자에서 과거 아토피 질환은 4명의 환자에서만 발견이 되었지만(13%), 고IgE혈증과 집먼지 진드기에 대한 항체는 각각 56%, 61%에서 관찰되었다. 14명의 아토피성 척수염 환자는 비아토피성 척수염 환자와 비교해 볼 때, 다음과 같은 분명한 차이를 보여 주었다. (1) 발병연령이 젊은 점(39 years vs. 51 years; p<0.0001), (2) 비급성 발현 (13/14 vs. 5/15; p=0.002) 과 입원당시 긴 증상 지속기간 (76 days vs. 16 days; p<0.001), (3) (4) 낮은 EDSS 점수 (2.1 vs. 5.6; p<0.001), (5) 비정상 SEP의 낮은 빈도(2/14 vs. 11/15; p<0.005), 그리고 (6) 말초 혈액검사에서 증가된 호산구 비율 (5.0% vs. 1.0%; p<0.001). 아토피척수염 환자에서의 흔한 MRI 소견은 횡단면에서 전체 면적의 2/3 이상을 차지하는 타원형 (92%) 이며 주변부의 국소 조영증강 (92%) 양상을 보였으며, 척수의 세 분절 이상 (71%) 을 침범하며 부종을 동반 (71%) 하는 경향을 보였다. 결론: 고IgE혈증과 집먼지 진드기 특이 항체는 한국의 원인불명의 척수염 환자에서 상당히 많이 존재했으며 아토피 척수염 환자는 비교적 균일한 임상, 혈척학적 그리고 방사선학적 양상을 보여 주었다. 특히, 모든 아토피 척수염 환자의 뇌 MRI에서 다발성 경화증이나 시신경 척수염을 시사하는 소견이 없었다. 따라서 우리의 연구는 아토피 척수염이 다발성 경화증이나 시신경 척수염과는 다른 병인을 가진 하나의 질환이라는 것을 시사한다."ABSTRACT i TABLE OF CONTENTS iii LIST OF FIGURES v LIST OF TABLES vi Ⅰ. INTRODUCTION 1 Ⅱ. PATIENTS AND METHODS 3 A. PATIENTS 3 B. CLINICAL ASSESSMENT 3 C. MEASUREMENT OF TOTAL AND SPECIFIC IGE LEVEL 4 D. MEASUREMENT OF NMO-IGG 4 E. MRI 4 F. STATISTICAL ANALYSIS 5 Ⅲ. RESULTS 6 A. COMPARISON OF TOTAL IgE AND MITE-SPECIFIC IgE BETWEEN MYELITIS AND NORMAL CONTROL 6 B. COMPARISON OF CLINICAL FEATURES BETWEEN PATIENTS WITH AND WITHOUT AM 10 C. COMPARISION OF MRI FINDINGS BETWEEN PATIENTS WITH AND WITHOUT AM 13 D. TREATMENT 18 E. PROGNOSIS 18 Ⅳ. DISCUSSION 21 REFERENCES 26 국문요약 33 "Maste

HgCdTe photovoltaic 적외선 감지소자 제작 및 수소화처리를 통한 특성 향상

학위논문(박사) - 한국과학기술원 : 전기 및 전자공학과, 1996.2, [ vii, 103 p. ]HgCdTe is the most generally used material for detecting infrared because of its capability of tailoring bandgap energy for the detecting wavelength by controlling the composition, a large electron mobility, and high normalized detectivity. This thesis describes the process of developing HgCdTe photovoltaic photodiode from 1990 to 1995. The characteristics of devices fabricated in early days showed increasing reverse bias leakage current with decreasing temperature and saturated RoA value at low temperature. As a method to find the sources of leakage current, current modeling was performed which includes diffusion current, generation current, direct tunneling current, and trap assisted tunneling current. The leakage current modeling can be well coincident with the leakage current of fabricated photodiodes. It is noteworthy in the leakage current modeling that the trap assisted tunneling current is dominant leakage current term in the substrate of which concentration is higher than $1 \times 10^{16} / cm^3$. From this result, devices with good characteristics could be fabricated by using the wafers with low carrier concentration and by decreasing the process temperature. To eliminate the problem of increased carrier concentration by vaporizing Hg from the wafer, decreasing process temperature is needed. In order to develop device with good characteristics, various test processes have been done. One of method to see the effects of those test processes on the HgCdTe device is measuring the minority carrier diffusion length. A new method for measuring the steady - state effective minority carrier diffusion length is proposed in this thesis. The diffusion length is extracted by means of measuring photocurrents which reduce exponentially with the distance between the junction edge and the region into which the environmental infrared penetrates. The region exposed to infrared radiation can be defined by the shape of the optical shadow mask (OSM). When the thickness of...한국과학기술원 : 전기 및 전자공학과