• Title/Summary/Keyword: disease mapping

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Pharmacophore Mapping and Virtual Screening for SIRT1 Activators

  • Sakkiah, Sugunadevi;Krishnamoorthy, Navaneethakrishnan;Gajendrarao, Poornima;Thangapandian, Sundarapandian;Lee, Yun-O;Kim, Song-Mi;Suh, Jung-Keun;Kim, Hyong-Ha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.30 no.5
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    • pp.1152-1156
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    • 2009
  • Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

Comparing Quantitative EEG and Low Resolution Electromagnetic Tomography Imaging between Deficit Syndrome and Non-Deficit Syndrome of Schizophrenia (정신분열병의 결핍증후군과 비결핍증후군에서 QEEG와 sLORETA를 이용한 비교연구)

  • Lee, Sang-Eun;Yim, Seon-Jin;Lee, Mi-Gyung;Lee, Jae-Won;Han, Kyu-Hee;Lee, Jong-Il;Sim, Min-Young;Yoon, Hai-Joo;Shin, Byoung-Hak
    • Sleep Medicine and Psychophysiology
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    • v.17 no.2
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    • pp.91-99
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    • 2010
  • Objectives: Deficit schizophrenia (DS) constitutes a disease separate from non-deficit schizophrenia (NDS). The aim of the current study was to compare the quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging between DS and NDS. Methods: This study was performed by 32 channels EEG for 42 schizophrenia patients who we categorized into DS and NDS using proxy instrument deficit syndrome (PDS). We performed the absolute power spectral analyses for delta, theta, alpha, low beta and high beta activities. We compared power spectrum between two groups using Independent t-test. Partial correlation test was performed with clinical parameters. Standardized LORETA (sLORETA) was used for comparison of cortical activity, and statistical nonparametric mapping (SnPM) was applied for the statistical analysis. Results: DS showed significantly increased delta and theta absolute power in fontal and parietal region compared with NDS (p<0.05). Power spectrum showed significant correlation with 'anergia' and 'hostility/suspiciousness' subscale of brief psychiatric rating scale (BPRS)(p<0.05). sLORETA found out the source region (anterior cingulate cortex/limbic part) that delta activity was significantly increased in DS (p=0.042). Conclusions: DS showed different cortical activity compared with NDS. Our results may suggest QEEG and LORETA could be the marker in differentiating between DS and NDS.

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Diode laser surgery in the treatment of oral proliferative verrucous leukoplakia associated with HPV-16 infection

  • Bombeccari, Gian Paolo;Garagiola, Umberto;Candotto, Valentina;Pallotti, Francesco;Carinci, Francesco;Gianni, Aldo Bruno;Spadari, Francesco
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.40
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    • pp.16.1-16.5
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    • 2018
  • Background: Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder, characterized by multifocal expression, progressive clinical evolution, and a high rate of malignant transformation. Evidence-based information regarding optimal PVL management is lacking, due to the paucity of data. The present report describes a case of PVL associated with HPV-16 infection and epithelial dysplasia treated by diode laser surgery, and the outcome of disease clinical remission over a 2-year follow-up period. Case report: A 61-year-old Caucasian male with oral verrucous hyperkeratosis presented for diagnosis. The lesions were localized on the maxillary gingiva and palatal alveolar ridge. Multiple biopsy specimens have been taken by mapping the keratotic lesion area. Microscopic examination was compatible with a diagnosis of PVL with focal mild dysplasia, localized in the right maxillary gingiva. Polymerase chain reaction (PCR) was done for human papillomavirus (HPV) detection which revealed presence of HPV DNA, and the genotype revealed HPV 16 in the sample. The PVL in the right gingival area was treated on an outpatient basis by excision with a diode laser. This approach resulted in good clinical response and decreased morbidity over a 2-year follow-up period. Conclusions: This case illustrates the benefit of a conservative approach by diode laser treatment than wide surgical excision for management of the PVL lesions associated with mild dysplasia and HPV-16 infection.

SRC-Stat Package for Fitting Double Hierarchical Generalized Linear Models (이중 다단계 일반화 선형모형 적합을 위한 SRC-stat의 사용)

  • Noh, Maengseok;Ha, Il Do;Lee, Youngjo;Lim, Johan;Lee, Jaeyong;Oh, Heeseok;Shin, Dongwan;Lee, Sanggoo;Seo, Jinuk;Park, Yonhtae;Cho, Sungzoon;Park, Jonghun;Kim, Youkyung;You, Kyungsang
    • The Korean Journal of Applied Statistics
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    • v.28 no.2
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    • pp.343-351
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    • 2015
  • We introduce how to fit random effects models via a SRC-Stat statistical package. This package has been developed to fit double hierarchical generalized linear models where mean and dispersion parameters for the variance of random effects and residual variance (overdispersion) can be modeled as random-effect models. The estimates of fixed effects, random effects and variances are calculated by a hierarchical likelihood method. We illustrate the use of our package with practical data-sets.

Some Properties of an Isolate of Peanut stunt virus Isolated from White Clover (Trifolium repens L.) (토끼풀에서 분리한 Peanut stunt virus의 성질)

  • Jung, Goo-Ho;Jeon, Yong-Woon;Choi, Jang-Kyung;Hong, Jin-Sung;Ryu, Ki-Hyun;Lee, Sang-Yong
    • Research in Plant Disease
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    • v.14 no.1
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    • pp.71-75
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    • 2008
  • An isolate of Peanut stunt virus (PSV), named as Tr-PSV, was isolated from white clover (Trifolium repens L) showing mosaic symptom. Tr-PSV systemically infected all plants tested in the Nicotiana spp. and induced local lesions on inoculated leaves of Chenopodium amaranticolor. However, Tr-PSV induced typical mosaic symptoms as ER-PSV on Vigna unguiculata 5 to 6 days after inoculation, while Fny-CMV used as a control virus of Cucumovirus produced local lesions on inoculated leaves. In dsRNA analysis, Tr-PSV consisted of four dsRNAs, but satellite RNA was not detected. The cDNA of coat protein gene of Tr-PSV was amplified by RT-PCR using a Cucumovirus-specific single pair primers that designed to amplify a DNA fragment of approximately 950 bp. By restriction mapping analysis using RFLP of the RT-PCR products and by serological properties of gel diffusion test, Tr-PSV belongs to a typical member of PSV subgroup I. This is the first report on the occurrence of PSV in white clover in Korea.

Development of Molecular Markers Conferring Bacterial Leaf Pustule Resistance Gene, rxp, using Resistant and Susceptible Cultivars in Soybean (콩 불마름병 저항성 및 감수성 품종을 이용한 rxp 유전자 근접 분자표지 개발)

  • Yang, Kiwoung;Lee, Yeong Hoon;Ko, Jong Min;Jeon, Myeong Gi;Lee, Byong Won;Kim, Hyun Tae;Yun, Hong Tae;Jung, Chan Sik;Baek, In Youl
    • Korean Journal of Breeding Science
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    • v.43 no.4
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    • pp.282-287
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    • 2011
  • Bacterial pustule (BP) is a leaf disease of soybean that is most common in Korea. Inoculation of 8ra, pathogen strain, to resistant and susceptible cultivars for finding the BP resistance gene (rxp) was much tried but the sequence of the exact gene is not found. This research performed in order to confirm the rxp gene near molecular marker by using the resistant and susceptible cultivars. Soybean BP resistance gene which related to region of near molecular marker could select the resistant cultivar. For the near molecular marker of rxp, reference genomics data available at sequenced Phytozome was used for designing molecular markers. The rxp was mapped between Satt372 and Satt486 on chromosome 17. According to previous study, rxp released in find mapping 7.2 Mbp to 7.3 Mbp on chromosome 17. In this study, we developed 3 random markers near from 6.6 Mbp to 7.3 Mbp on chromosome 17 identified to increase the genetic resolution of the rxp gene region using resistant and susceptible cultivars. Particularly, Rxp17-700 marker was mostly coincided resistance and susceptible genotype to rxp. This result suggests that Rxp17-700 marker will be more tightly linked to rxp gene.

Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice

  • Ahreum Lee;Duck Kyun Yoo;Yonghee Lee;Sumin Jeon;Suhan Jung;Jinsung Noh;Soyeon Ju;Siwon Hwang;Hong Hee Kim;Sunghoon Kwon;Junho Chung;Youngnim Choi
    • IMMUNE NETWORK
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    • v.21 no.5
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    • pp.34.1-34.16
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    • 2021
  • Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

Current Status and Future Perspective of PET (PET 이용 현황 및 전망)

  • Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.1-7
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    • 2002
  • Positron Emission Tomography (PET) is a nuclear medicine imaging modality that consists of systemic administration to a subject of a radiopharmaceutical labeled with a positron-emitting radionuclide. Following administration, its distribution in the organ or structure under study can be assessed as a function of time and space by (1) defecting the annihilation radiation resulting from the interaction of the positrons with matter, and (2) reconstructing the distribution of the radioactivity from a series of that used in computed tomography (CT). The nuclides most generally exhibit chemical properties that render them particularly desirable in physiological studies. The radionuclides most widely used in PET are F-18, C-11, O-15 and N-13. Regarding to the number of the current PET Centers worldwide (based on ICP data), more than 300 PET Centers were in operation in 2000. The use of PET technology grew rapidly compared to that in 1992 and 1996, particularly in the USA, which demonstrates a three-fold rise in PET installations. In 2001, 194 PET Centers were operating in the USA. In 1994, two clinical and research-oriented PET Centers at Seoul National University Hospital and Samsung Medical Center, was established as the first dedicated PET and Cyclotron machines in Korea, followed by two more PET facilities at the Korea Cancer Center Hospital, Ajou Medical Center, Yonsei University Medical Center, National Cancer Center and established their PET Center. Catholic Medical School and Pusan National University Hospital have finalized a plan to install PET machine in 2002, which results in total of nine PET Centers in Korea. Considering annual trends of PET application in four major PET centers in Korea in Asan Medical Center recent six years (from 1995 to 2000), a total of 11,564 patients have been studied every year and the number of PET studies has shown steep growth year upon year. We had 1,020 PET patients in 1995. This number increased to 1,196, 1,756, 2,379, 3,015 and 4,414 in 1996,1997,1998,1999 and 2000, respectively. The application in cardiac disorders is minimal, and among various neuropsychiatric diseases, patients with epilepsy or dementia can benefit from PET studios. Recently, we investigated brain mapping and neuroreceptor works. PET is not a key application for evaluation of the cardiac patients in Korea because of the relatively low incidence of cardiac disease and less costly procedures such as SPECT can now be performed. The changes in the application of PET studios indicate that, initially, brain PET occupied almost 60% in 1995, followed by a gradual decrease in brain application. However, overall PET use in the diagnosis and management of patients with cancer was up to 63% in 2000. The current medicare coverage policy in the USA is very important because reimbursement policy is critical for the promotion of PET. In May 1995, the Health Care Financing Administration (HCFA) began covering the PET perfusion study using Rubidium-82, evaluation of a solitary pulmonary nodule and pathologically proven non-small cell lung cancer. As of July 1999, Medicare's coverage policy expanded to include additional indications: evaluation of recurrent colorectal cancer with a rising CEA level, staging of lymphoma and detection of recurrent or metastatic melanoma. In December of 2001, National Coverage decided to expand Medicare reimbursement for broad use in 6 cancers: lung, colorecctal, lymphoma, melanoma, head and neck, and esophageal cancers; for determining revascularization in heart diseases; and for identifying epilepsy patients. In addition, PET coverage is expected to further expand to diseases affecting women, such as breast, ovarian, uterine and vaginal cancers as well as diseases like prostate cancer and Alzheimer's disease.

Relationship between Brain Perfusion SPECT and MMSE Score in Dementia of Alzheimer's Type: A statistical Parametric Mapping Analysis (알쯔하이머형 치매환자에서 SPM 방법을 이용한 뇌 관류 SPECT와 정신-인지기능 수행성능의 상관)

  • Kang, Hye-Jin;Lee, Dong-Soo;Kang, Eun-Joo;Lee, Jae-Sung;Yeo, Seong-Seok;Kim, Jin-Yeong;Lee, Dong-Woo;Cho, Maeng-Je;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.2
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    • pp.91-101
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    • 2002
  • Purpose : The aim of this study was to identify the brain areas in which reductions of regional cerebral blood flow (rCBF) were correlated with decline of general mental function, measured by Mini-Mental State Examination (MMSE). Materials and Methods : Tc-99m HMPAO brain SPECT was peformed in 9 probable AD patients at the initial and follow-up periods of 1.8 years (average) after the first study. MMSE scores were also measured in both occasions. The mean MMSE score of the initial study 16.4 (range: 5 - 24) and the mean MMSE score of the follow-up was 8.1 (range: 0 - 17). Each SPECT image was normalized to the cerebellar activity and a correlation analysis was peformed between the level of rCBF in AD patients and the MMSE scores by voxel-based analysis using SPM99 software. Results : Significant correlation was found between the blood-flow decrease in left inferior prefrontal region (BA 47) and left middle temporal legion (BA 21) and the MMSE score changes. Additional areas such as anterior and posterior cingulate cortices, precuneus, and bilateral superior and middle prefrontal regions showed the similar trends. Conclusions : A relationship was found between reduction of regional cerebral blood flow in left prefrontal and temporal areas and decline of cognitive function in Alzheimer's disease(AD) patients. This voxel-based analysis is useful in evaluating the progress of cognitive function in Alzheimer's disease.

Assessment of Hyperperfusion by Brain Perfusion SPECT in Transient Neurological Deterioration after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis Surgery (천측두동맥-중대뇌동맥 문합술 후 발생한 일과성 신경학적 악화에서 뇌관류 SPECT를 이용한 과관류 평가)

  • Lee, Jeong-Won;Kim, Yu-Kyeong;Lee, Sang-Mi;Eo, Jae-Sun;Oh, Chang-Wan;Lee, Won-Woo;Paeng, Jin-Chul;Kim, Sang-Eun
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.4
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    • pp.267-274
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    • 2008
  • Purpose: Transient neurological deterioration (TND) is one of the complications after extracranial-intracranial bypass surgery, and it has been assumed to be caused by postoperative transient hyperperfusion. This study was performed to evaluate the relationship between TND and preoperative and postoperative cerebral perfusion status on brain perfusion SPECT following superficial temporal artery - middle cerebral artery (STA-MCA) anastomosis surgery. Materials and Methods: A total of 60 STA-MCA anastomosis surgeries of 56 patients (mean age: $50{\pm}16$ yrs; M:F=29:27; atherosclerotic disease: 33, moyamoya disease: 27) which were done between September 2003 and July 2006 were enrolled. The resting cerebral perfusion and cerebral vascular reserve (CVR) after acetazolamide challenge were measured before and 10 days after surgery using 99mTc-ethylcysteinate dimer (ECD) SPECT. Moreover, the cerebral perfusion was measured on the third postoperative day. With the use of the statistical parametric mapping and probabilistic brain atlas, the counts for the middle cerebral artery (MCA) territory were calculated for each image, and statistical analyses were performed. Results: In 6 of 60 cases (10%), TND occurred after surgery. In all patients, the preoperative cerebral perfusion of affected MCA territory was significantly lower than that of contralateral side (p=0.002). The cerebral perfusion on the third and tenth day after surgery was significantly higher than preoperative cerebral perfusion (p=0.001, p=0.02). In TND patients, basal cerebral perfusion and CVR on preoperative SPECT were significantly lower than those of non-TND patients (p=0.01, p=0.05). Further, the increases in cerebral perfusion on the third day after surgery were significant higher than those in other patients (p=0.008). In patients with TND, the cerebral perfusion ratio of affected side to contralateral side on third postoperative day was significantly higher than that of other patients (p=0.002). However, there was no significant difference of the cerebral perfusion ratio on preoperative and tenth postoperative day between patients with TND and other patients. Conclusion: In patients with TND, relative and moderate hyperperfusion was observed in affected side after bypass surgery. These finding may help to understand the pathophysiology of TND.