• 대한의생명과학회지
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• 제25권2호
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• pp.177-184
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• 2019

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase and GTPase domains. A pathogenic G2019S mutation that is the most prevalent among the LRRK2 mutations and is also found in sporadic cases, increases its kinase activity. Therefore, identification of LRRK2 kinase substrates and the development of kinase inhibitors are under intensive investigation to find PD therapeutics. Several recent studies have suggested members of Rab proteins, a branch of the GTPase superfamily, as LRRK2 kinase substrates. Rab proteins are key regulators of cellular vesicle trafficking. Among more than 60 members of human Rab proteins, Rab3, Rab5, Rab8, Rab10, Rab12, Rab29, Rab35, and Rab43 have been identified as LRRK2 kinase substrates. However, most studies have used human embryonic kidney (HEK) 293T cells overexpressing LRRK2/Rab proteins or murine embryonic fibroblast (MEF) cells which are not relevant to PD, rather than neuronal cells. In this study, we tested whether Rab proteins are phosphorylated by LRRK2 in astroglia in addition to neurons. Among the various Rab substrates, we tested phosphorylation of Rab10, because of the commercial availability and credibility of the phospho-Rab10 (pRab10) antibody, in combination with a specific LRRK2 kinase inhibitor. Based on the results of specific LRRK2 kinase inhibitor treatment, we concluded that LRRK2 phosphorylates Rab10 in the tested brain cells such as primary neurons, astrocytes and BV2 microglial cells.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2006년도 The 6th Intermational Symposium on Developmental Biotechnology
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• pp.59-59
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• 2006

• Journal of Korean Neurosurgical Society
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• 제30권9호
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• pp.1079-1085
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• 2001

Objective : We analysed various surgical approaches and surgical results of 28 middle cranial base tumors for the purpose of selecting optimal surgical approach to the middle cranial base tumor. Methods : In this retrospective review, 28 patients, including 16 meningioma, 6 trigeminal neurinoma, 2 pituitary adenoma, 2 craniopharyngioma, 1 facial neurinoma, and 1 metastatic tumor, underwent surgical treatment using skull base technique. Of theses, 16 tumors were mainly confined to middle cranial fossae, 5 tumors with extension into both anterior and middle fossa, and 7 tumors with extension into both middle and posterior fossa. Tumors that confined to the middle cranial fossa or extended into the anterior cranial fossa were operated with modified pterional, orbitozygomatic or Dolen'c approach, and tumors that extended into the posterior cranial fossa were operated with anterior, posterior or combined transpetrosal approach. Completeness of tumor resection, surgical outcome, postoperative complication, and follow up result were studied. Results : Total tumor removal was achieved in 9 tumors of 10 tumors that did not extended to the cavernous sinus, and was achieved in 7 tumors of 8 tumors that extended to the lateral wall of the cavernous sinus. Of 10 tumors that extended to the venous channel of the cavernous sinus, only 2 were removed totally. Surgical outcome was excellent in 14 patients, good in 10, fair in 2 and poor in 2. There were no death in this series. Dumbell type tumor which extended into both middle and posterior fossae showed tendency of poor prognosis as compared with tumors that confined middle cranial fossa and extended into both anterior and middle cranial fossa. Postoperative dysfunctions were trieminal hypesthesia in 3, oculomotor nerve palsy in 2, abducens nerve palsy in 2, hemiparesis in 2, cerebellar sign in 1, facial palsy in 1 and hearing impairment in 1. Conclusion : Based on our findings and a review of the literature, we conclude that, when selecting the surgical approach to the middle cranial fossa tumors, the most important factors to be considered were exact location of the tumor mass and existence of the cavernous sinus invasion by tumor mass. We recommend modified pterional or orbitozygomatic approach in cases with tumors located anterior and middle cranial base, without cavernous sinus invasion. In cases with tumors invading into cavernous sinus, we recommend Dolen'c or orbitozygomatic approach. And in lateral wall mass and the cavernous sinus, it is preferred to approach the tumor extradurally. For the tumor involing with middle fossa and posterior fossa(dumbell type) a combined petrosal approach is necessary. In cases with cavernous sinus invasion and internal carotid artery encasement, we recommend subtotal resection of the tumor and radiation therapy to prevent permanent postoperative sequele.

• Journal of Korean Neurosurgical Society
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• 제30권sup2호
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• pp.189-196
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• 2001

목 적 : 교모세포종은 흔한 원발성 뇌종양이며 생물학적 특성상 빠른 성장률을 보이는 것 외에 침습성이 강하여 종양과 인접한 부분을 파괴 시킬 뿐 아니라 직접접촉하지 않는 부분의 파괴도 일어나게 되어 치료 예후가 매우 불량한 것으로 되어 있다. 광역학치료는 광감각제를 이용하며 광감각제는 적절한 파장의 광원에 노출되면 세포 내에서 산소독성 물질을 생성하여 세포괴사를 유도하는 것이 주 살해작용의 기전이다. 본 실험에서는 사람의 신경교종 세포주인 U87 세포를 이용하여 실험관 내에서 광감각제 photofrin을 이용한 광역학치료가 종양의 침습성에 미치는 영향을 알아보고 동시에 이를 뇌종양치료의 새로운 방법으로 사용될 수 있는지의 여부를 알아보고자 하였다. 재료 및 방법 : 교모세포종 세포주인 U87 세포를 여러 농도의 photofrin으로 처리한 후 632nm $100mJ/cm^2$의 고정된 광선조건에서 본 실험을 시행 하였으며 Microculture tetrazolium(MTT) assay를 이용하여 세포 살해능력을 측정하고 침습성은 matrigel artificial basement membrane assay 및 tumor spheroid fetal rat brain aggregate(FRBA) confrontation assay를 이용하여 측정하였다. 결 과 : MTT assay를 이용하여 측정한 광역학 치료의 세포살해능력은 $100mJ/cm^2$의 광선 세기에서 광감각제인 photofrin의 농도에 비례하여 세포 살해 능력을 보였다. Matrigel artificial basement membrane assay 를 이용한 종양 침습성 검사에서 광역학치료가 종양침습의 억제효과를 나타냄을 알 수 있었으며 특히 세포 살해능력을 별로 보이지 않았던 photofrin 농도 2.5ug/ml에서 뚜렷한 침습억제효과를 나타내고 있었다(p<0.05). tumor spheroid fetal rat brain aggregate(FRBA) confrontation assay에서는 brain aggregate의 파괴와 종양의 침습을 관찰할 수 있었는데 파괴의 모양은 생체내에서 보이는 것과 비슷 하였다. 또한 그 정도와 범위는 처리된 Photofrin의 농도에 비례하여 종양침습이 억제됨을 알 수 있었다. 결 론 : 이러한 결과를 종합해 보았을 때 PDT는 종양세포의 침습성에 중요한 역할을 함을 알 수 있었으며 PDT 는 세포 살해능력뿐 아니라 침습성에도 영향을 미침으로써 종양 치료에 유용한 방법으로 사용될 수 있을 것으로 사료된다.

• 대한치매학회지
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• 제17권4호
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• pp.163-173
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• 2018

Background and Purpose: Behavioral variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia, which has clinical symptoms of progressive personality and behavioral changes with deterioration of social cognition and executive functions. The pathology of bvFTD is known to be tauopathy or TDP-43 equally. We analyzed the $^{18}F-THK5351$ positron emission tomography (PET) scans, which were recently developed tau PET, in patients with clinically-diagnosed bvFTD. Methods: Forty-eight participants, including participants with behavioral variant frontotemporal dementia (bvFTD, n=3), Alzheimer's disease (AD, n=21) and normal cognition (NC, n=24) who completed 3T magnetic resonance images, $^{18}F-THK5351$ PET scans, and detailed neuropsychological tests were included in the study. Voxel-wise statistical analysis and region of interest (ROI)-based analyses were performed to evaluate the retention of THK in bvFTD patients. Results: In the voxel-based and ROI-based analyses, patients with bvFTD showed greater THK retention in the prefrontal, medial frontal, orbitofrontal, anterior cingulate, insula, anterior inferior temporal and striatum regions compared to NC participants. Left-right asymmetry was noted in the bvFTD patients. A patient with extrapyramidal symptoms showed much greater THK retention in the brainstem. Conclusions: The distribution of THK retention in the bvFTD patients was mainly in the frontal, insula, anterior temporal, and striatum regions which are known to be the brain regions corresponding to the clinical symptoms of bvFTD. Our study suggests that $^{18}F-THK5351$ PET imaging could be a supportive tool for diagnosis of bvFTD.

• Journal of Korean Neurosurgical Society
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• 제30권1호
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• pp.41-46
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• 2001

Objective : The exact position of the lesion during the pallidotomy is critical to obtain the clinical improvement of parkinson's disease without damage to surrounding structure. Ventriculogrphy, CT(computed tomograpy) or MRI(magnetic resonance imaging) have been used to determine the initial coordinates of stereotactic target for pallidotomy. The goal of this study was to determine whether microelectrode recording significantly improves the neurophysiologic localization of the target obtained from MRI. Methods : Twenty patients were studied. They underwent a unilateral pallidotomy. Leksell frame was applied and T1 axial images parallel to the AC-PC(anterior commissure-posterior commissure) plane using a 1.5 Tesla MRI with 3mm slice thickness were obtained. Anteroposterior coordinate of target was chosen at 2mm in front of the midcommissural point and lateral coordinate between 19 and 22mm from the midline. The vertical coordinate was calculated on coronal slice using a fast spin echo inversion recovery sequence(FSEIR) related to the position of the choroidal fissure and ranged over 4-5mm below the AC-PC plane. Confirmation of the anatomical target was done on axial slices using the same FSEIR sequence . Microrecording was done at the pallidum contralateral to the symptomatic side using an electrode with a tip diameter of $1{{\mu}m}$ diameter tip and 1.1-1.4 mOhm impedance at 1000Hz. Electrophysiologic localization of the target was also confirmed intraoperatively by macrostimulation. Results : Microrecording techniques were reliable to define the transition from the base of the pallidum which was characterized by the disappearance of spike activity and by the change of the audible background activity. Signals from high amplitude neurons firing at 200-400Hz were recorded in the pallidal base. X, Y and Z coordinates of target obtained from the MRI were within 1mm from the X, Y, Z coordinates obtained with microrecording in 16 patients (80%), 15 patients(75%), 10 patients(50%) respectively. The difference of Y coordinate between on MRI and on microrecording was 4mm in only one patient. Conclusion : The MRI was accurate to localize the target within 1mm of the error from microrecording target in 70% of the patients. 4mm discrepancy was observed only once. We conclude that MRI alone can be used to determine the target for pallidotomy in most patients. However, microrecording technique can still be extremely valuable in patents with aberrant anatomy or unusual MRI coordinates. We also consider physiologic confirmation of the target using macrostimulation to be mandatory in all cases.

• 대한한의학회지
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• 제28권1호통권69호
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• pp.72-86
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• 2007

Objectives : The purpose of this study was to evaluate and compare the cost-effectiveness of Eastern, Western, and collaborative treatments and suggest a cost-effective approach for patients with frozen shoulder pain. Methods : Using the data of fifty-two patients, treatment effectiveness was measured by CSA, SPABI, and ROM scales and changes from the baseline score were evaluated. Data source for cost estimation was based on the national health insurance (NHI) payment system. Because the price in NHI was differentiated by health care institutions, five collaborative types were considered in assessing costs. Cost-effective ratios were computed for economic evaluation. Results : Compared with Eastern treatment, collaborative and Western treatments showed better effects on CSA scale after 4 weeks' treatment. The collaborative approach was also the most effective treatment on SPADI and ROM scales. The direct cost per patient receiving Eastern treatment was less than other treatments. In general, collaborative treatment dominated Eastern and Western treatments in cost-effectiveness an analysis. However, the cost-effectiveness ratio of Eastern treatment resulted in \9,000 compared to \29,000 of collaborative treatment on SPADI. Four different indicators of ROM scales resulted in different approaches as the cost-effective treatment. Conclusions : Considering cost-effectiveness ratios, collaborative treatment was the best treatment on CSh and SPADI scales after 4 weeks' treatment. As for ROM scales, the recommended alternatives were Eastern treatment for patients with abduction and adduction disabilities, Western treatment for those with flexion disability, and collaborative approach fir those with extension disabiliry.

• Journal of Acupuncture Research
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• 제23권5호
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• pp.219-228
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• 2006

Objectives : To observe the effect of acupuncture treatment on Digital Infrared Thermographic Imaging(DITI) in frozen shoulder patients. Methods : 17 voluntary patients received acupuncture treatment on LI15, TE14, GB21 and Master Dong's acupuncture points, Shin-gwan and Gyun-joong, twice a week for 4 weeks. The patients were instructed to practice self exercise during their daily lives. Evaluations were made before treatment, after 1 week of treatment, after 2 weeks, 3 weeks and after 4 weeks of treatment. Constant Shoulder Assessment(CSA), Shoulder Pain and Disability Index(SPADI), Range of Motion(ROM) and the patient's satisfaction concerning the treatment was measured by Visual Analogue Scale(VAS). DITI was measured before treatment and after 4weeks of treatment. The obtained data was analyzed. Results : CSA, SPADI, VAS, adduction and extension showed significant(p<0.05) improvement. Abduction and flexion both improved after 4 weeks of treatment, but the improvement was statistically insignificant(p>0.05). DITI showed improvement but the improvement was insignificant(p>0.05). Conclusion : 4 weeks of acupuncture treatment significantly improved CSA, SPADI, VAS, adduction and extension in frozen shoulder patients(p<0.05). The improvement of abduction and flexion after 4 weeks of acupuncture treatment was insignificant(p>0.05). DITI results improved after 4 weeks of acupuncture treatment. But the change of thermal difference was insignificant(p>0.05).

• Journal of Acupuncture Research
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• 제23권5호
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• pp.177-185
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• 2006

Objectives : To observe the effect of acupuncture treatment and western medical treatment on frozen shoulder patients. Methods : 39 voluntary patients were randomly assigned to the Eastern treatment group(E group, n=22) and the Western treatment group(W group, n=17). The E group received acupuncture treatment on LI15, TE14, GB21 and Master Dong's acupuncture points, Shin-gwan and Gyun-joong, twice a week for 4 weeks. The W group received suprascapular nerve block, subacromial injection and trigger point injection, twice a week for 4 weeks. Both groups were instructed to practice self exercise during their daily lives. Evaluations were made before treatment and after treatment using Constant Shoulder Assessment(CSA), Shoulder Pain and Disability Index(SPADI) and the patient's satisfaction concerning the treatment was measured by Visual Analogue Scale(VAS). The obtained data were analyzed and compared. Results : The E group showed significant improvement(p<0.05) according to the CSA and SPADI. The patient's satisfaction scored 5.67 on a scale of 10. The W group showed significant improvement(p<0.05) according to the CSA and SPADI. The patient's satisfaction scored 7.73. But the difference between the two groups were insignificant according to CSA and SPADI. Conclusion : Both acupuncture and nerve block treatment significantly improved frozen shoulder. But the difference of the two treatments was insignificant.

• 대한중풍순환신경학회지
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• 제14권1호
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• pp.15-22
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• 2013

■ Objectives The aim of this study is to look into the correlation between motor performance and displacement of center of pressure(CoP) in hemiplegic patients with cerebral stroke. ■ Methods We measured manual muscle test(MMT) as motor performance value and, anterior/posterior position(Ant./Post. position) and lateral symmetry of CoP as displacement of CoP values from 129 stroke patients. The gait analysis was carried out using treadmill gait analysis equipment. ■ Results In terms of motor performance, MMT of upper extremity negatively correlated with Ant/Post position of CoP, however, one of lower extremity did not. In addition, MMT of both extremities negatively correlated with lateral symmetry of CoP. ■ Conclusion Displacement of CoP was negatively correlated with hemiplegic patient's motor performance.