• Title/Summary/Keyword: Target Disease

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Pallidotomy Guided by MRI and Microrecording for Parkinson's Disease (파킨슨환자의 자기공명영상과 미세전극기록을 이용한 담창구 파괴술)

  • Lee, Kyung Jin;Son, Hyung Sun;Park, Sung Chan;Cho, Kyung Keun;Park, Hae Kwan;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
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    • v.30 no.1
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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.

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Potent HAT Inhibitory Effect of Aqueous Extract from Bellflower (Platycodon grandiflorum) Roots on Androgen Receptor-mediated Transcriptional Regulation

  • Lee, Yoo-Hyun;Kim, Yong-Jun;Kim, Ha-Il;Cho, Hong-Yon;Yoon, Ho-Geun
    • Food Science and Biotechnology
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    • v.16 no.3
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    • pp.457-462
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    • 2007
  • Histone acetyltransferase (HAT) is a family of enzymes that regulate histone acetylation. Dysfunction of HAT plays a critical role in the development of cancer. Here we have screened the various plant extracts to find out the potent HAT inhibitors. The bellflower (Platycodon grandiflorum) root have exhibited approximately 30% of the inhibitory effects on HAT activity, especially p300 and CBP (CREB-binding protein) at the concentration of $100\;{\mu}g/mL$. The cell viability was decreased approximately 52% in LNCaP cell for 48 hr incubation. Furthermore, mRNA level of 3 androgen receptor target genes, PSA, NKX3.1, and TSC22 were decreased with bellflower root extract treatment ($100\;{\mu}g/mL$) in the presence of androgen. In ChIP assay, the acetylation of histone H3 and H4 in PSA promoter region was dramatically repressed by bellflower root treatment, but not TR target gene, Dl. Therefore, the potent HAT inhibitory effect of bellflower root led to the decreased transcription of AR target genes and prostate cancer cell growth with the repression of histone hyperacetylation.

RNA Interference in Infectious Tropical Diseases

  • Kang, Seok-Young;Hong, Young-S.
    • Parasites, Hosts and Diseases
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    • v.46 no.1
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    • pp.1-15
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    • 2008
  • Introduction of double-stranded RNA (dsRNA) into some cells or organisms results in degradation of its homologous mRNA, a process called RNA interference (RNAi). The dsRNAs are processed into short interfering RNAs (siRNAs) that subsequently bind to the RNA-induced silencing complex (RISC), causing degradation of target mRNAs. Because of this sequence-specific ability to silence target genes, RNAi has been extensively used to study gene functions and has the potential to control disease pathogens or vectors. With this promise of RNAi to control pathogens and vectors, this paper reviews the current status of RNAi in protozoans, animal parasitic helminths and disease-transmitting vectors, such as insects. Many pathogens and vectors cause severe parasitic diseases in tropical regions and it is difficult to control once the host has been invaded. Intracellularly, RNAi can be highly effective in impeding parasitic development and proliferation within the host. To fully realize its potential as a means to control tropical diseases, appropriate delivery methods for RNAi should be developed, and possible off-target effects should be minimized for specific gene suppression. RNAi can also be utilized to reduce vector competence to interfere with disease transmission, as genes critical for pathogenesis of tropical diseases are knockdowned via RNAi.

Phosphorylation of REPS1 at Ser709 by RSK attenuates the recycling of transferrin receptor

  • Kim, Seong Heon;Cho, Jin-hwa;Park, Bi-Oh;Park, Byoung Chul;Kim, Jeong-Hoon;Park, Sung Goo;Kim, Sunhong
    • BMB Reports
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    • v.54 no.5
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    • pp.272-277
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    • 2021
  • RalBP1 associated EPS domain containing 1 (REPS1) is conserved from Drosophila to humans and implicated in the endocytic system. However, an exact role of REPS1 remains largely unknown. Here, we demonstrated that mitogen activated protein kinase kinase (MEK)-p90 ribosomal S6 Kinase (RSK) signaling pathway directly phosphorylated REPS1 at Ser709 upon stimulation by epidermal growth factor (EGF) and amino acid. While REPS2 is known to be involved in the endocytosis of EGF receptor (EGFR), REPS1 knockout (KO) cells did not show any defect in the endocytosis of EGFR. However, in the REPS1 KO cells and the KO cells reconstituted with a non-phosphorylatable REPS1 (REPS1 S709A), the recycling of transferrin receptor (TfR) was attenuated compared to the cells reconstituted with wild type REPS1. Collectively, we suggested that the phosphorylation of REPS1 at S709 by RSK may have a role of the trafficking of TfR.

A promising therapeutic strategy for metastatic gestational trophoblastic disease: Engineered anticancer gene-expressing stem cells to selectively target choriocarcinoma (Review)

  • Gyu-Sik Kim;Kyung-A Hwang;Kyung-Chul Choi
    • Oncology Letters
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    • v.17 no.3
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    • pp.2576-2582
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    • 2019
  • Gestational trophoblastic disease (GTD) is an unusual disease occurring in pregnancy that originates from abnormal trophoblastic cells and comprises a group of diseases with different properties of invasion, metastasis and recurrence. The GTD group includes hydatidiform moles and gestational trophoblastic neoplasms (GTNs), with GTNs being divided into invasive moles, choriocarcinoma, placental site trophoblastic tumors and epithelioid trophoblastic tumors. The present review focuses on current effective treatments for GTD, including conventional and novel promising direct enzyme prodrug therapies (DEPTs). Conventional therapies, such as chemotherapy and hysterectomy, are currently used in a clinical setting; however, the use of diverse DEPTs, including antibody-DEPT and gene-DEPT is also being attempted to cure GTNs. In addition, gene delivery tools using genetically engineered neural stem cells (NSCs) are presently being examined for the treatment of GTNs. The tumor-tropism of NSCs by chemoattractant factors is a unique characteristic of these cells and can serve as a vehicle to deliver anticancer agents. Previous studies have demonstrated that injection with NSC-expressing suicide genes into xenograft animal models has a significant inhibitory effect on tumor growth. Stem cells can be genetically engineered to express anticancer genes, which migrate to the metastatic sites and selectively target cancer cells, and are considered to effectively target metastatic GTNs. However, the safety issue of stem cell therapy, such as tumorigenesis, remains a challenge. Novel therapies comprising a combination of conventional and novel promising treatments are anticipated to be definitive treatments for metastasized and/or recurrent patients with GTNs.

A Target Leaf Spot Disease Caused by Corynespora cassiicola on Cucumber Cultivated in Green House (시설하우스에서 Corynespora cassiicola에 의해 발생하는 오이 갈색무늬병)

  • Kwon, Mi-Kyung;Yang, Kwang-Yeol;Cho, Baik-Ho
    • Research in Plant Disease
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    • v.10 no.2
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    • pp.121-125
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    • 2004
  • An epidemic of target leaf spot of cucumber (Cucumis sativus) occurred in commercial greenhouses in Korea in 2000/2001. The early symptoms on the leaves were small brown spots with yellow halos. These lesions became irregular enlarging in diameter and eventually defoliation resulted. The causal agent was a fungus with morphological characteristics matching Corynespora cassiicola. The sequence of the ITS region of C. cassiicola CM2000-1 was identical to that of an authentic strain of Corynespora cassiicola. Optimal germination of spores and mycelial growth on plate was at 3$0^{\circ}C$. A long dew period on the leaf surface and high temperatures were the main contributing factors for disease development and the greenhouse epidemic. Artificial inoculation of the Korean isolate of C. cassiicola revealed resistance in some Korean cucumber cultivars.

Homology Modeling of CCR 4: Novel Therapeutic Target and Preferential Maker for Th2 Cells

  • Shalini, M.;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.7 no.4
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    • pp.234-240
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    • 2014
  • C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

Pathogenic Molecular Mechanisms of Glutamatergic Synaptic Proteins in Alzheimer's Disease (알츠하이머 병과 글루타메이트성 시냅스 단백질의 분자적 질환 기전)

  • Yang, Jin-Hee;Oh, Dae-Young
    • Korean Journal of Biological Psychiatry
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    • v.17 no.4
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    • pp.194-202
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    • 2010
  • Alzheimer's disease(AD) is the most common neurodegenerative disorder and constitutes about two thirds of dementia. Despite a lot of effort to find drugs for AD worldwide, an efficient medicine that can cure AD has not come yet, which is due to the complicated pathogenic pathways and progressively degenerative properties of AD. In its early clinical phase, it is important to find the subtle alterations in synapses responsible for memory because symptoms of AD patients characteristically start with pure impairment of memory. Attempts to find the target synaptic proteins and their pathogenic pathways will be the most powerful alternative strategy for developing AD medicine. Here we review recent progress in deciphering the role of target synaptic proteins related to AD in hippocampal glutamatergic synapses.

Influence of review system using computerized program for Acute Respiratory Infection upon practicing doctors' behaviour (전산프로그램을 이용한 급성호흡기감염증 청구자료 심사 시행 후 개원의의 진료 및 청구 행태 변화)

  • Chung Seol-Hee;Park Eun-Chul;Jeong Hyoung-Sun
    • Health Policy and Management
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    • v.16 no.2
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    • pp.49-76
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    • 2006
  • The aim of this study was to explore the effects of a computerized review program which was introduced in August 1, 2003, using claims data for acute respiratory infection related diseases. National Health Insurance (NHI) claims data on respiratory infection related diseases before and after the introduction, with six month intervals respectively, were used for the analysis. Clinic was the unit of observation, and clinics with only one physician whose specialty was internal medicine, pediatrics, otorhinolaryngology and family medicine and clinics with a general practitioner were selected. The final sample had 7,637 clinics in total. Indices used to measure practice pattern was prescription rates of antibiotics, prescription rates of injection drug per visit, treatment costs per claim, and total costs per claim. Changes in the number of claims for major disease categories and upcoding index for disease categories were used to measure claiming behavior. Data were analysed using descriptive analysis, t-test for indices changes before and after the introduction, analysis of variance (ANOVA) for practice pattern change for major disease categories, and multiple regression analysis to identify whether new system influenced on provider' practice patterns or not. Prescription of antibiotics, prescription rates of injection drug, treatment costs per claim, and total costs per claim decreased significantly. Results from multiple regression analysis showed that a computerized review system had effects on all the indices measuring behavior. Introduction of the new system had the spillover effects on the provider's behavior in the related disease categories in addition to the effects in the target diseases, but the magnitude of the effects were bigger among the target diseases. Rates of claims for computerized review over total claims for respiratory diseases significantly decreased after the introduction of a computerized review system and rates of claims for non target diseases increased, which was also statistically significant. Distribution of the number of claims by disease categories after the introduction of a computerized review system changed so as to increase the costs per claims. Analysis of upcoding index showed index for 'other acute lower respiratory infection (J20-22)', which was included in the review target, decreased and 'otitis media (H65, H66)', which was not included in the review target, increase. Factors affecting provider's practice patterns should be taken into consideration when policies on claims review method and behavior changes. It is critical to include strategies to decrease the variations among providers.

In silico High-Throughput Screening by Hierarchical Chemical DB Search by 3D Pharmacophore Model

  • Shin, Jae-Min
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.181-182
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    • 2002
  • Recentadvancesin '-omics ' technologies enable us to discover more diverse disease- relevant target proteins, which encourages us to find out more target-specific novel lead compounds as new drug candidates. Therefore, high-throughput screening (HTS) becomes an essential tool in this area. Among many HTS tools, in silico HTS is a very fast and cost-effective tool to try to derive a new lead compound for any new targets, especially when the target protein structures are known or readily modeled. (omitted)

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