• 대한한방내과학회지
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• 제25권3호
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• pp.461-472
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• 2004

Objectives : For the screening of neuroprotective effects of medicinal herbs, the complex system of animal models suffer some disadvantages in controlling critical parameters such as blood pressure and body temperature. Additionally, application of drugs to the appropriate brain area sometimes is difficult, due to poor permeability though the blood brain barrier, and so potential protective effects might be masked. Methods : Organotypic hippocampal slice culture (OHSC) method has the advantages of being relatively easy to prepare and of maintaining the general structure, including tissue integrity and the connections between cells. Drugs can easily be applied and neuronal damage can easily be quantified by using tissues and culture media. This study demonstrates neuroprotective effects of Puerariae radix (葛根, PR), Salviae miltiorrhizae radix (丹蔘, SR), Rhei rhizoma (大黃, RR), and Bupleuri radix (柴胡, BR). These were screenedand compared to MK-801, antagonist of NMDA receptors, by using OHSC of 1 week-old Sprague-Dawley rats. Oxygen/glucose deprivation (OGD) were conducted in an anaerobic chamber $(85%\;N_2,\;10%\;CO_2\;and\;5%\;H_2)$ in a deoxygenated glucose-free medium for 60 minutes. Water extracts of each herbs were treated to culture media with $5\;{\mu}g/ml$ for 48 hours. Results : Neuronal cell death in the cultures was monitored by densitometric measurements of the cellular uptake of propidium iodide (PI). PI fluorescence images were obtained at 48 hours after the OGD and medicinal herb treatment. Also TUNEL-positive cells in the CAI and DG regions and LDH concentrations in culture media were measured at 48 hours after the OGD. According to measured data, MK-801, PR, SR and BR demonstrated significant neuroprotective effect against excessive neuronal cell death and apoptosis induced by the OGD insult. Especially, PR revealed similar neuroprotective effect to MK-801 and RR demonstrated weak neuroprotective effect. Conclusions : These results suggest that OHSC can be a suitable method for screening of neuroprotective effects of medicinal herbs. (This work was supported by the research program of Dongguk University and Grant 01-PJ9-PG1-01CO03-0003 from Ministry of Health & Welfare.)

• 생명과학회지
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• 제19권8호
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• pp.1055-1061
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• 2009

${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) 수용체는 중추신경계에 널리 발현하며, 연접부위에서 글루타메이트에 의한 흥분성 신경전달의 역할을 행한다. 이러한 수용체의 조절은 학습과 기억에 관여한다. 본 연구에서는 AMPA receptor subunit glutamate receptor-interacting protein 1 (GRIP1)과 결합하는 단백질로 armadillo family인 p0071/plakophilin-4을 분리하였다. GRIPl 단백질은 p0071/plakophilin-4 단백질의 C-말단과 결합하며, armadillo family 단백질 중 p0071/plakophilin-4 과만 결합한다. 효모 two-hybrid assay에서 GRIPl의 Postsynaptic density-95/Discs large/Zona occludens-1 (PDZ) 영역이 p0071/plakophilin-4 단백질과의 결합에 관여하며, p0071/plakophilin-4 단백질의 C-말단 아미노산인 "S-X-V" 배열이 결합에 필수적이었다. 이러한 결합은 뇌 균질액에서 Glutathione S-transferase (GST) pull-down assay와 공면역침강법으로 확인하였다. 이러한 결과들은 AMPA 수용체가 연접후막에 안정적으로 위치하는 새로운 역할을 시사한다.

• 생명과학회지
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• 제20권7호
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• pp.1005-1011
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• 2010

$\gamma$-aminobutyric acid (GABA)는 중추신경계에서 억제성으로 작용하는 주요한 신경전달물질이다. GABA 수송체(GAT)는 연접간격에 존재하는 GABA를 세포 내로 재 흡수하여 GABA의 농도를 조절한다. 그런데 GABA 수송체가 어떻게 조절되는지는 아직 밝혀지지 않았다. 본 연구에서는 효모 two-hybrid system을 사용하여 뇌의 주요 GABA 수송체인 GAT1의 C-말단과 특이적으로 결합하는 ubiquitin-specific protease 14 (Usp14)를 분리하였다. Usp14는 GABA 수송체 GAT1및 GAT2와는 결합하지만, 다른 GAT isoform과는 결합하지 않았다. GAT1과의 결합에는 Usp14의 C-말단부위가 필수적으로 관여함을 확인하였다. 또한 이 단백질간의 결합을 GST pull-down assay로 확인하였으며, 생쥐 뇌 균질액의 co-immunoprecipitation을 통하여 in vivo에서도 GAT1과 Usp14가 결합함을 확인하였다. 이러한 결과들은 Usp14가 GAT1과 결합하여 세포막에 존재하는 GAT1의 수를 조절하는 역할을 할 가능성을 시사한다.

• 농업생명과학연구
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• 제46권6호
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• pp.137-146
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• 2012

본 연구는 중간대뇌동맥을 폐쇄한 대뇌허혈성 손상모델에서 ferulic acid에 의해 조절되는 HO-1과 HO-2의 발현에 관하여 조사하였다. 흰쥐(Sprague-Dawley, 수컷)에 ferulic acid (100 mg/kg) 또는 vehicle을 중간대뇌동맥폐쇄술(MCAO) 후 정맥으로 주사하였고 중간대뇌동맥폐쇄술(MCAO)을 실시한 24시간 후 대뇌피질의 조직을 적출하였다. Hematoxylin과 eosin 염색을 통하여 MCAO로 유도된 뇌 손상시 ferulic acid의 보호효과를 확인하였다. MCAO을 시행한 대뇌피질에서는 응축된 핵과 신경세포의 괴사 소견을 보였으나, ferulic acid 투여군에서는 이들 신경세포의 병변을 현저히 완화시켰다. HO-1과 HO-2의 RNA와 단백질 발현의 변화를 reverse-transcription PCR과 Western blot으로 분석하였다. HO-1 발현은 MCAO 후 vehicle 투여군에서 현저히 감소하였으나, MCAO 후 ferulic acid를 투여한 실험군에서는 이들 감소의 완화를 보였으며, MCAO를 시행하지 않은 실험군의 수준으로 유지되었다. 그러나, HO-2의 발현은 MCAO 후 vehicle 투여군과 ferulic acid 투여군에서 유의적인 차이는 관찰되지 않았고 MCAO를 시행하지 않은 실험군의 수준으로 유지되었다. 따라서, 본 연구의 결과는 허혈성 뇌 손상시 ferulic acid는 HO-1 발현을 조절하였으나, HO-2의 발현에는 영향을 미치지 못함을 확인하였다. 결론적으로, 허혈성 뇌손상시 ferulic acid는 HO-1의 발현을 조절하여 신경세포를 보호하는 역할을 수행한다는 사실을 확인하였다.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.321-330
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• 2021

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

• 대한근전도전기진단의학회지
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• 제20권2호
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• pp.106-111
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• 2018

Transcranial magnetic stimulation (TMS) has been a gold standard for investigating central motor pathways in humans. Diffusion tensor imaging with fiber tractography (DTI FT) is known for its usefulness in detecting white matter lesion in vivo. We investigated the clinical usefulness of elucidating the integrity and continuity of corticospinal tract (CST) by combined use of TMS and DTI FT in this study. We report two cases who have presented with left hemiparesis and evaluated by both TMS and DTI FT; 10-year-old boy with Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episode syndrome and 20-year-old woman with traumatic brain injury. Combined use of TMS and DTI FT successfully led to localize the brain lesion that might cause motor impairment in patients with abnormal signal intensities in MRI. The results of this study suggest that TMS and DTI FT might provide the detailed information between function and anatomy of the CST, complementarily.

• 동양고전연구
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• 제37호
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• pp.345-375
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• 2009

조선에서는 서양 의학이 전래되면서 동양적인 신체관과 서양적인 신체관이 자연스럽게 습합하기도 하고, 양자가 상호 대립하면서 논점을 형성하기도 하였다. 18세기 이래로 형성되기 시작한 주요 논점으로는 두 가지를 꼽을 수 있다. 하나는 서양 해부학의 효과를 얼마나 긍정하는가의 문제이고, 다른 하나는 지각(知覺)을 주관하는 것이 심장인가 뇌인가의 문제이다. 이런 논점은 서양의 신체관을 타자화하는 것이면서, 그것을 통해 동양의 전통적 신체관을 정식화하는 것이기도 했다. 조선에서 서양 의학의 영향이나 신체관의 변화가 뚜렷한 진전을 보인것은 최한기(崔漢綺)에 이르러서였다. 그의 새로운 신체관의 특징은 두 가지로 요약할 수 있다. 하나는 신체에 대해 기계론적인 관점을 강조하는 것이고, 다른 하나는 신체의 지각 능력을 강조하는 것이다. 그러나 그의 기계론적 신체관은 신기론(神氣論)의 간섭을 받고, 지각설은 신기균형설(神氣均衡說)이라 할 수 있는 다소 애매한 측면을 가지고 있었다. 이러한 신체관은 그가 서양 의학과 신기 개념의 접합을 통해 새롭게 확립한 것이지만, 양자 사이의 접합이 완전했다고 보기는 어려운 면이 있었다. 이 점은 그가 의학의 기초로 생각한 물리학 방면에서도 그대로 나타났다. 그는 화학원소론과 기론의 접합을 추구했지만, 궁극적으로 신기론의 유기체론적 성격을 포기하지 않는 한 그 접합은 성공하기 어려웠다. 그런 만큼 최한기의 새로운 신체관 역시 불완전한 임시 건조물의 성격을 벗어날 수 없는 것이었다. 그러나 기계론과 유기체론의 접합이라는 그의 시도 자체는, 그 문제가 오늘날까지 해소되지 않고 있는 거대문제라는 점에서 사상사적 가치를 부인하기 어렵다고 할 수 있다.

• Korean Journal of Radiology
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• 제20권1호
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• pp.171-179
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• 2019

Objective: For localization of the motor cortex, seed-based resting-state functional MRI (rsfMRI) uses the contralateral motor cortex as a seed. However, research has shown that the location of the motor cortex could differ according to anatomical variations. The purpose of this study was to compare the results of rsfMRI using two seeds: a template seed (the anatomically expected location of the contralateral motor cortex) and a functional seed (the actual location of the contralateral motor cortex determined by task-based functional MRI [tbfMRI]). Materials and Methods: Eight patients (4 with glioma, 3 with meningioma, and 1 with arteriovenous malformation) and 9 healthy volunteers participated. For the patients, tbfMRI was performed unilaterally to activate the healthy contralateral motor cortex. The affected ipsilateral motor cortices were mapped with rsfMRI using seed-based and independent component analysis (ICA). In the healthy volunteer group, both motor cortices were mapped with both-hands tbfMRI and rsfMRI. We compared the results between template and functional seeds, and between the seed-based analysis and ICA with visual and quantitative analysis. Results: For the visual analysis, the functional seed showed significantly higher scores compared to the template seed in both the patients (p = 0.002) and healthy volunteers (p < 0.001). Although no significant difference was observed between the functional seed and ICA, the ICA results showed significantly higher scores than the template seed in both the patients (p = 0.01) and healthy volunteers (p = 0.005). In the quantitative analysis, the functional seed exhibited greater similarity to tbfMRI than the template seed and ICA. Conclusion: Using the contralateral motor cortex determined by tbfMRI as a seed could enhance visual delineation of the motor cortex in seed-based rsfMRI.

• 생물정신의학
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• 제12권2호
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• pp.207-215
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• 2005

Objectives:This study was to compare verbal memory ability among patients with schizophrenia, bipolar manic patients and unipolar depressive patients, and to understand their charicteristics of memory process. Methods:All subjects were hospitalized patients and had been interviewed by using the Structured Clinical Interview for DSM-IV(SCID). Schizophrenic patients(N=40), bipolar manic patients(N=17), and unipolar depressive patients(N=20) were assessed with K-AVLT for verbal memory and with K-WAIS for verbal IQ. Three groups were compared regarding total immediate recall, delayed recall, delayed recognition, learning curve, memory retention, and retrieval efficiency under controlled verbal IQ. Multiple regression analysis was performed to find which clinical factors have an influence on verbal memory ability. Results:In MANCOVA, differences of verbal memory test scores among the groups were statistically significant(F=1.800, p<.05). In post hoc analysis, Patients with schizophrenia and bipolar mania showed poorer performance in immediate recall, delayed recall, delayed recognition, retrieval efficiency than unipolar depres- sive patients. And schizophrenics performed poorly in delayed recall, delayed recognition, retrieval efficiency than nonpsychotic affective disorder group, but no difference in total immediate recall, delayed recall, delayed recognition, retrieval efficiency between the schizophrenic group and the psychotic affective group. Conclusions:These results partially confirm previous reports of verbal memory ability among major psychiatric disorders. Our results showed that psychotic symptoms were related with verbal memory, and longer duration of illness was related with poorer performance in schizophrenia and unipolar depression.

• Nuclear Medicine and Molecular Imaging
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• 제41권3호
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• pp.252-254
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• 2007

Image fusion is fast catching attention as Wagner pointed out in his 2006 version of the recent progress and development presented at the annual meeting of Society of Nuclear Medicine. Prototypical fusion of bone scan and radiograph was already attempted at in 1961 when Fleming et al. published an article on strontium-85 bone scan. They simply superimposed dot scan on radiograph enabling simultaneous assessment of altered bone metabolism and local bone anatomy. Indeed the parallel reading of images of bone scan and radiography, CT, MRI or ultrasonography has been practiced in nuclear medicine long since. It is fortunate that recent development of computer science and technology along with the availability of refined CT and SPECT machines has permitted us to open a new avenue to digitally produce precise fusion image so that they can readily be read, exchanged and disseminated using internet. Ten years ago fusion was performed using Bresstrahlung SPECT/CT and it is now achievable by PET/CT and SPECT/CT software and SPECT/CT hardware. The merit of image fusion is its feasibility of reliable assessment of morphological and metabolic change. It is now applicable not only to stationary organs such as brain and skeleton but also to moving organs such as the heart, lung and stomach. Recently, we could create useful fusion image of cardiac SPECT and 64-channel CT angiograph. The former provided myocardial metabolic profile and the latter vascular narrowing in two patients with coronary artery stenosis and myocardial ischemia. Arterial stenosis was severe in Case 1 and mild in Case 2.