• Investigative Magnetic Resonance Imaging
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• v.13 no.1
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• pp.40-46
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• 2009

Purpose : The purpose of this study was to investigate the quantitative evaluation of the corticospinal tract (CST) at the multiple levels by using functional MRI (fMRI) co-registered to diffusion tensor tractography (DTT). Materials and Methods : Ten normal subjects without any history of neurological disorder participated in this study. fMRI was performed at 1.5 T MR scanner using hand grasp-release movement paradigm. DTT was performed by using DtiStudio on the basis of fiber assignment continuous tracking algorithm (FACT). The seed region of interest (ROI) was drawn in the area of maximum fMRI activation during the motor task of hand grasp-release movement on a 2-D fractional anisotropy (FA) color map, and the target ROI was drawn in the cortiocospinal portion of anterior lower pons. We have drawn five ROIs for the measurement of FA and apparent diffusion coefficient (ADC) along the corona radiata (CR) down to the medulla. Results : The contralateral primary sensorimotor cortex (SM1) was mainly found to be activated in all subjects. DTT showed that tracts originated from SM1 and ran to the medulla along the known pathway of the CST. In all subjects, FA values of the CST were higher at the level of the midbrain and posterior limb of internal capsule (PLIC) than the level of others. Conclusion : Our study showed that co-registered fMRI and DTT has elucidated the state of CST on 3-D and analyzed the quantitative values of FA and ADC at the multiple levels. We conclude that co-registered fMRI and DTT may be applied as a useful tool for clarifying and investigating the state of CST in the patients with brain injury.

• Proceedings of the Ginseng society Conference
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• 2007.12a
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.526-535
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• 1992

Background: The oxygen radicals released by alveolar macrophages contribute to killing of microorganisms including M. tuberculosis. Macrophages are "primrd" for enhanced oxygen radical release by macrophage activator like IFN-$\gamma$ and LPS, which do not themselves cause release of oxygen radicals. Actural production of oxygen radicals is "triggered" by phagocytosis or by exposure to chemical stimuli like PMA or FMLP. There has been debates about the priming effect of alveolar macro phages because they are exposed to usual environmental particles unlike blood monocytes. Therefore we examined priming effect of IFN-$\gamma$ in human alveolar macrophages comparing with that in blood monocytes and rat alveolar macrophages. And we observed the alterations of superoxide production in both human and rat alveolar macrophages after exposure to M. tuberculosis H37Ra bacilli itself and its lysate. Methods: Bronchoalveolar lavage fluid was processed to isolate alveolar macrophages by adherence and the adherent cells were removed by cold shock method. After exposure to M. tuberculosis H37Ra strain, alveolar macrophages were incubated for 24 hours with IFN-$\gamma$. The amount of superoxide production stimulated with PMA was measured by ferricytochrome C reduction method. Results: 1) The priming effect in human alveolar macrophages was not observed even with high concentration of IFN-$\gamma$ while it was observed in blood monocytes and rat alveolar macrophages. 2) Both human and rat alveolar macrophages exposed to avirulent H37Ra strain showed triggering of superoxide release and similar results were shown with the exposure to H37Ra lysate. Conclusion: The priming effect in human alveolar macrophages is not observed because of its usual exposure to environmental particles and avirulent H37Ra strain does not inhibit the activation of alveolar macrophages.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1047-1057
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• 1998

Background : Sarcoidosis is a systemic granulomatous disorder of unknown origin and characterized by accumulation of T cells and macrophages. Various cytokines may play crucial roles in the activation of T cells and macrophages, and thereby in the formation of granulomas. However, little is known about the balance between proinflammatory cytokines and antiinflammatory cytokines in the development of sarcoid granulomas and disease activities. In the present study, we measured IL-6, IL-8 and IL-10 in the bronchoalveolar lavage fluid(BALF) from patients with pulmonary sarcoidosis to find out whether there is an imbalance between proinflammatory cytokines and antiinflammatory cytokines in the lung. Methods: Fourteen subjects with the diagnosis of sarcoidosis and six healthy volunteers were included. BALF was concentrated ten-fold by pressure ultrafiltration and each cytokine levels were measured by EUSA method. Active sarcoidosis was defined by major organ involvement or clinically progressive diseases. Results: The mean IL-6 levels in the BALF of the active sarcoidosis group were significantly increased than in controls or inactive sarcoidosis group(p<0.05). Meanwhile, the IL-8 levels were increased and IL-10 levels were decreased in the active sarcoidosis group than in controls or inactive sarcoidosis group without significance(p>0.05). In active pulmonary sarcoidosis patients, the IL-6 levels in BALF correlated with the BALF CD4/CD8 ratio(r=0.768, p<0.05) and IL-8 levels(r=0.564, p<0.05). Conclusions : The data presented showed that pro-inflammatory cytokine IL-6 is important in the pathogenesis of sarcoidosis and decreased tendency of anti-inflammatory cytokine IL-10 might also be involved in the development of granulomatous inflammation in sarcoidosis.

• Journal of Life Science
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• v.21 no.9
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• pp.1234-1243
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• 2011

Liriope platyphylla has been used in oriental medicine as an effective medical plant to improve symptoms of cough, sputum production, neurodegenerative disorders, obesity and diabetes for long time. In order to investigate the effects of novel extracts on nerve growth factors (NGF)-stimulated neuritic outgrowth, the alteration of NGF expression and NGF receptor signaling pathway were detected in neuroblastoma cells and C57BL/6 mice. Of a total of 13 novel extracts, 4 extracts (LP-E, LP-M, LP-M50, LP2E17PJ) showed high viability on MTT assay. Also, all of these extracts induced NGF secretion and NGF mRNA expression in neuroblastoma cells. However, the NGF-induced neuritic outgrowth from PC12 cells was only stimulated by LP-E, LP-M and LP-M50. Furthermore, we selected LP-M as a best candidate, based on method and amounts of extraction, in order to verify its effect in mice. C57BL/6 mice were treated with 50 mg/kg of LP-M for 2 weeks and the effects on NGF regulation were analyzed with various methods. The expression of NGF mRNA was significantly increased in LP-M treated mice compared to vehicle treated mice. Also, the signaling pathway of p75NTR was inhibited in the cortex by LP-M treatment, with no change in the hippocampus of brain. However, the signaling pathway of TrkA was dramatically activated in only hippocampus via LP-M treatment. Therefore, these results suggest that the novel four extracts of L. platyphylla may contribute to the regulation of NGF expression and secretion in neuronal cells. LP-M was especially considered to be an excellent candidate for a neurodegenerative disease-therapeutic drug.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.495-509
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• 2003

Background : Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor-${\kappa}B$ transcription factor, we hypothesized that nuclear factor-${\kappa}B$ might be related to the reduced neutrophil apoptosis observed in sepsis. Methods : Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches : by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-${\kappa}B$ was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. Results : We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after cycloheximide treatment, suggesting that decreased spontaneous neutrophil apoptosis is dependent on de novo protein synthesis. In patients with sepsis, basal neutrophil nuclear factor-${\kappa}B$ was activated compared to the level in healthy controls. Moreover, a blockade of nuclear factor-${\kappa}B$ activity reversed the decreased spontaneous neutrophil apoptosis in sepsis patients. Meanwhile, X-linked inhibition of apoptosis expression, which is regulated by nuclear factor-${\kappa}B$, decreased 24 hours after incubation in healthy persons, but persisted for 24 hours in patients with sepsis. Conclusion : These observations suggest that the reduced spontaneous neutrophil apoptosis observed in patients with sepsis may be related to the induction of survival protein by nuclear factor-${\kappa}B$.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.2
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• pp.1200-1206
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• 2015

The major target for drug discovery, G-protein coupled receptor (GPCR) is involved in many physiological activities and related to various diseases and disorders. Among experimental techniques relating to the GPCR drug discovery process, various cell-based screening methods are influenced by cell conditions used in the overall process. Recently, the utilization of frozen cells is suggested in terms of reducing data variation and cost-effectiveness. The aim of this study is to evaluate various conditions in cell freezing such as temperature conditions and storage terms. The stable cell lines for calcium sensing receptor and urotensin receptor were established followed by storing cultured cells at $-80^{\circ}C$ up to 4 weeks. To compare with cell stored at liquid nitrogen, agonist and antagonist responses were recorded based on the luminescence detection by the calcium induced photoprotein activation. Cell signals were reduced as the storage period was increased without the changes in $EC_{50}$ and $IC_{50}$ values $EC_{50}:3.46{\pm}1.36mM$, $IC_{50}:0.49{\pm}0.15{\mu}M$). In case of cells stored in liquid nitrogen, cell responses were decreased comparing to those in live cells, however changes by storage periods and significant variations of $EC_{50}/IC_{50}$ values were not detected. The decrease of cell signals in various frozen cells may be due to the increase of cell damages. From these results, the best way for a long-term cryopreservation is the use of liquid nitrogen condition, and for the purpose of short-term storage within a month, $-80^{\circ}C$ storage condition can be possible to adopt. As a conclusion, the active implementation of frozen cells may contribute to decrease variations of experimental data during the initial cell-based screening process.

• The Korean Journal of Nuclear Medicine
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• v.36 no.6
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• pp.317-324
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• 2002

Purpose: The use of statistical parametric mapping (SPM) program has increased for the analysis of brain PET and SPECT images. Montreal Neurological Institute (MNI) coordinate is used in SPM program as a standard anatomical framework. While the most researchers look up Talairach atlas to report the localization of the activations detected in SPM program, there is significant disparity between MNI templates and Talairach atlas. That disparity between Talairach and MNI coordinates makes the interpretation of SPM result time consuming, subjective and inaccurate. The purpose of this study was to develop a program to provide objective anatomical information of each x-y-z position in ICBM coordinate. Materials and Methods: Program was designed to provide the anatomical information for the given x-y-z position in MNI coordinate based on the Statistical Probabilistic Anatomical Map (SPAM) images of ICBM. When x-y-z position was given to the program, names of the anatomical structures with non-zero probability and the probabilities that the given position belongs to the structures were tabulated. The program was coded using IDL and JAVA language for 4he easy transplantation to any operating system or platform. Utility of this program was shown by comparing the results of this program to those of SPM program. Preliminary validation study was peformed by applying this program to the analysis of PET brain activation study of human memory in which the anatomical information on the activated areas are previously known. Results: Real time retrieval of probabilistic information with 1 mm spatial resolution was archived using the programs. Validation study showed the relevance of this program: probability that the activated area for memory belonged to hippocampal formation was more than 80%. Conclusion: These programs will be useful for the result interpretation of the image analysis peformed on MNI coordinate, as done in SPM program.

• The Korean Journal of Emergency Medical Services
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• v.13 no.3
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• pp.41-58
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• 2009

Objective : The purpose of this study is to identify actual operations and issues of wireless paging system operation for the aged living alone as the end users of wireless paging system primarily in Gwangyang city, and thereby to explore possible advanced and integrated ways to promote social safety network for the aged. Methods : The survey tool used in this study was a structured questionnaire form consisting of question items. The researcher hereof conducted this survey by means of direct visit and interview during two seasons, i.e. from February to August, 2008 and from December 2008 to March 2009, respectively. Results : 1) For general demographic characteristics, it was found that 90.9% of all respondents were women and 61.2% of all respondents were at age 75 to 84. for health conditions, it was found that more than 90% of all respondents often took medicines due to their unhealthy body, and most of respondents suffered from musculoskeletal diseases 79.3% and circulatory diseases 61.6%. for walking capacity, it was found that 45.5% of all respondents used walking aids, and disable respondents (11.5% of all respondents) were represented primarily by those with physical disability (52.6% of disable respondents). for actual use of medical institutions, it was found 47.3% of all respondents relied on local clinics, since they preferred neighborhood hospitals or clinics they can trust for medical care. for social activities and supports, it was found that 43.6% respondents had 'needs for assistance at times' and 33.9% respondents have 'no need for assistance'. And it was found that the major difficulties in living alone at old age were represented primarily by health problems 37.8% and economic difficulties 33.5%. 2) For characteristics related to wireless paging system, it was found that 90.3% respondents used wireless paging system recommended by firemen, and 28.5% respondents used this system. and it was found that 59.6% respondents used this system once, and 85.2% respondents used it because of acute or chronic diseases. more than 90% respondents thought that they knew about wireless paging system and considered themselves safe, but 83.6% respondents didn't attach a remote control on their upper clothes, and even 49.1% respondents turned off the power of wireless paging system due to their concern about electricity bill and noise. 3) It was found that 83.6% respondents felt it necessary to use wireless paging system, and wireless paging users felt more satisfied with using the system than non-users, and 50.7% showed high satisfaction at certain psychological benefits like 'confidence in coping with critical situations' and 'a sense of relief'. In addition, it was found that some respondents who answered that 'they didn't turn off the paging system as they knew how it works' and those who answered that they knew 'how to use it' showed relatively high satisfaction. And some respondents who kept it well and felt it necessary also showed high satisfaction. 4) It was found that the level of satisfaction our respondents felt with using wireless paging system varied significantly availability($x^{2}$ = 12.759, p = .002), psychological advantages($x^{2}$ = 12.174, p = .002), knowledge about how to use system($x^{2}$ = 7.021, p = .016), power on/off($x^{2}$ = 13.221, p = .001), level of knowledge about system($x^{2}$ = 21.002, p = .000), maintenance($x^{2}$ = 9.871, p = .007) and level of necessity($x^{2}$ = 34.939, p = .000) on the statistical basis.

• Journal of Yeungnam Medical Science
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• v.22 no.2
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• pp.166-182
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• 2005

Background: Cyclin-dependent kinase (CDK) inhibitors are family of molecules that regulate the cell cycle. The CDKN2, a CDK4 inhibitor, also called p16, has been implicated in human tumorigenesis. The CDKN2 inhibits the cyclin/CDK complexes which regulate the transition from G1 to S phase of cell cycle. There is a previous report that homozygous deletion of CDKN2 region on chromosome 9p21 was detected frequently in astrocytoma, glioma and osteosarcoma, less frequently in lung cancer, leukemia and ovarian cancer, but not detected in colon cancer and neuroblastoma. However, little is known about the relationship between CDKN2 and laryngeal cancer. Therefore this study was initiated to investigate the role of CDKN2 in human laryngeal squamous cell carcinoma development.1) Materials and methods: We used 5 human laryngeal carcinoma cell lines whether they have deletions or losses of CDKN2 gene expression by DNA-PCR or RT-PCR, respectively. We examined 8 fresh frozen human laryngeal cancer tissues to detect the loss of heterozygosity (LOH) of CDKN2. PCR was performed by using microsatellite markers of short arm of human chromosome 9 (D9S126, D9S144, D9S156, D9S161, D9S162, D9S166, D9S171, D9S200 and D9SIFNA). For informative cases, allelic loss was scored if the signal of one allele was significantly decreased in tumor DNA when compared to the same allele in normal DNA. Results: The CDKN2 DNA deletion was observed in 3 cell lines. The CDKN2 mRNA expression was observed in only one cell line, which was very weak. LOH was detected in 7 cases (87.5%). Conclusion: These results suggest that CDKN2 plays a role in the carcinogenesis of human laryngeal squamous cell carcinoma.