• IMMUNE NETWORK
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• v.5 no.2
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• pp.78-88
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• 2005

Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.1
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• pp.5-16
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• 2002

Background : Though mononuclear phagocytes serve as the final effectors in killing intracellular Mycobacterium tuberculosis, the bacilli readily survive in the intracellular environment of resting cells. The mechanisms through which cellular activation results in the intracellular killing is unclear. In this study, we sought to explore an in vitro model of a low-level infection of human mononuclear phagocytes with MAC and $H_{37}Ra$ and determine the extent of the lymphocyte dependent cytotoxicity of human monocytes and alveolar macrophages. Materials and Methods : The peripheral monocytes were prepared using the Ficoll gradient method from PPD positive healthy people and tuberculosis patients. The alveolar macrophages were prepared from PPD positive healthy people via a bronchoalveolar lavage. The human mononuclear phagocytes were infected at a low infection rate (bacilli:phagocyte 1:10) with MAC(Mycobacterium avium) and Mycobacterium tuberculosis $H_{37}Ra$. Non-adherent cells(lymphocyte) were added at a 10:1 ratio. After 1,4, and 7 days culture in $37^{\circ}C$, 5% CO2 incubator, the cells were harvested and inoculated in a 7H10/OADC agar plate for the CFU assay. The bacilli were calculated with the CFU/$1{\times}10^6$ of the cells and the cytotoxicity was expressed as the log killing ratio. Results : The intracellular killing of MAC and $H_{37}Ra$ within the monocyte was greater in patients with tuberculosis compared to the PPD positive controls (p<0.05). Intracellular killing of MAC and $H_{37}Ra$ within the alveolar macrophage appeared to be greater than that within the monocytes of the PPD positive controls. There was significant lymphocyte dependent inhibition of intracellular growth of the mycobacteria within the monocytes in both the controls and tuberculosis patients and within the macrophages in the controls(p<0.05). There was no specific difference in the virulence between the MAC and the $H_{37}Ra$. Conclusion : This study is an in vitro model of a low-level infection with MAC and $H_{37}Ra$ of human mononuclear phagocytes. The intracellular cytotoxicity of the mycobacteria within the phagocytic cells was significantly lymphocyte dependent. During the 7 days culture after the intracellular phagocytosis, the actual confinement of the mycobacteria was observed within the monocytes of tuberculosis patients and the alveolar macrophages of the controls as in the case of adding lymphocytes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.498-506
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• 2014

The objective of this study was to investigate the beneficial effects of mulberry extract (MBE) on blood flow improvement. The $SC_{50}$ value for the DPPH radical scavenging activity of MBE was $89.36{\pm}5.46{\mu}g/mL$. Analysis of the cellular toxicity of MBE on RAW 264.7 and HepG2 cells showed no toxicity under a concentration of 2,500 ${\mu}g/mL$. We found that MBE inhibited the enzyme activity of cyclooxygenase (COX)-2 as well as oxidation of human LDL. Western blotting analysis showed that MBE inhibited protein expression of COX-2 and 5-lipoxygenase in RAW 264.7 cells. In addition, MBE inhibited protein expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, MBE reduced the serum levels of total cholesterol and C-reactive protein in a concentration-dependent manner. These results both in vitro and in vivo suggest that MBE can be employed for the improvement of blood flow.

• BMB Reports
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• v.36 no.1
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• pp.82-94
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• 2003

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

• Childhood Kidney Diseases
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• v.4 no.1
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• pp.48-56
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• 2000

Purpose: Alport SD., the most common herectitary rephriris, is a renal disease with rapid progression. Deafness, ocular abnormalities and a specific EM finding may be associated in addition to a family history. We have aralyged retrospectively. Methods: We observed 12 children with Alport syndrome who were diagnosed at Dept. of pediatrics in Kyunghee Univ., College of Medicine, from Apr. 1991 until Jun. 1999. We used four criteria for diagnosis: renal disease, family history, deafness or eye abnormalities, and a specific finding in electron microscopy Results: 2 of 12 patients had all features of the four diagnostic criteria. We could not trace an exact family history in 3 patients, and 6 patients did not exhibit deafness or eye abnormality. One could not have renal biopsy because offer chronic renal failure. Other three criteria were observed in her. The ratio of male to female observed was 1:2 respectively and the mean age of initial renal symptom was 5.6 years. 9 of 12 patients had a family history of renal disease. In the audiogram and ocular examination for 11 of 12 cases, sensorineural hearing loss was observed in 6 and ocular abnormality in 2 cases. In electron microscopic finding, irregular thickness of the capillary basement membranes with lamination of lamina densa and foot process obliteration was noted in 9 of 11 and thin basement membrane with splitting and foot process obliteration was noted in the other 2. The mean period of follow-up was 3 6/12 years. And one patient developed the chronic renal failure until now and had kidney transplantation. Conclusion: For the diagnosis of Alport syndrome, the following four diagnostic criteria are very important : renal disease, family history, deafness or eye abnormalities, and a specific finding on electron microscopy. We expect that more patients can be detected through the analysis of these characteristics.

• The Korean Journal of Mycology
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• v.29 no.1
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• pp.15-21
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• 2001

This study was conducted to investigate the immunomodulatory activities of proteoglycan extracted from cultured mycelia of Ganoderma lucidum IY009. The proteoglycan contained two polymer peaks, one was the higher MW peak of 2,000 kD and the other was low peaks of 12kD. To understand the part of strong pharmaceutical activity between two peak, the proteoglycan was separated by ultrafiltration and column chromatography and then examined the various pharmaceutical effects. High molecular weight fraction possesing high content of ${\beta}-linked$ glucan was exhibited high antitumor activity, against sarcoma 180 bearing ICR mouse. And also, anticomplementary activity was highly observed in high molecule fraction than low it fraction. When the raw 264.7 and murine peritoneal macrophage treated with low fraction, high fraction and other stimuli. The activities inducing tumor necrosis factor of the high factions were $2.2{\sim}2.5$ times stronger than that of low fraction.

• Journal of Nutrition and Health
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• v.40 no.7
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• pp.593-600
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• 2007

Recent studies described the ${\varepsilon}4$ allele of apoE confers a two-to fourfold increased risk for late-onset Alzheimer#s disease (LOAD), but LOAD pathology does not all fit neatly around apo E. Therefore, the goal of this study was to find the association between Alzheimer and apo E4 genotype in the 107 elderly between 50 to 64 years old who visited to FHWC of Sungshin Women#s University. We conducted the questionnaire survey (general & 24 hr dietary recall), anthropometerics (BP, waist & BMI) and blood biochemistry (FBS & lipid profiles). LDL-c and HOMA-IR were calculated by Friedwald#s and Matthew#s formulas. The apo E genotyping was performed by PCR-RFLP method and subjects were divided into three allele groups (${\varepsilon}3$; wild, ${\varepsilon}2$ & ${\varepsilon}4;$ mutants). The apo E allele frequencies were 7.0% for the ${\varepsilon}2$, 83.6% for the ${\varepsilon}3$ and 9.3% for the ${\varepsilon}4$. In comparison with biochemistry characteristics by apo E genotype, FBS was significantly higher in ${\varepsilon}4(129.2{\pm}6.8)$ than that in the others (${\varepsilon}2$: $117{\pm}7.4$, ${\varepsilon}3$: $107.3{\pm}2.2)$ (p<0.01). More than forty percents of ${\varepsilon}4$ group shown the dyslipidemia [high TG (>150mg/dl) & low HDL (<40 mg/dl:male or <50 mg/dl: female)]. The cytokines levels such as IL-1 ${\beta}$, IL-6 and $TNF-{\alpha}$ were not different among three apoE alleles. After the adjusting sex, age & dietary fiber, LDL-c level was siginificantly higher in ${\varepsilon}4$ ($108.3{\pm}7.7$) than that in ${\varepsilon}2$ ($100.4{\pm}8.4$) (p<0.05). According to food intake and the recipe on the basis of 24 hr dietary recall, the elder]y with ${\varepsilon}4$ allele took higher intake frequency of the light -colored vegetable (radish, onion & cabbage) and pan-fried foods (sauteed beef and vegetables, stir-fried vienna with vegetables) than the others. We knew that the elderly with ${\varepsilon}4$ allele had been restricted the calories intakes with high dietary fiber (33.6+2.5 g/d) to maintain the normal level of FBS and LDL-c. On next study, the prevalence of Alzheimer#s disease in this population who has ${\varepsilon}4$ allele on the condition of calories restriction will be continually follow-up.

• Journal of Nutrition and Health
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• v.48 no.2
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• pp.157-166
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• 2015

Purpose: The effects of water extract and distillate from the mixture of black goat meat and medicinal herb on MG-63 osteoblast proliferation and mouse bone marrow derived osteoclast formation were investigated. Methods: Proximate composition, volatile basic nitrogen (VBN), mineral content, free amino acid composition and free fatty acid composition in black goat meat were determined. Water extract and distillate were prepared with three groups; goat meat only (BG-E, BG-D), six herbs added group (BG-E6, BG-D6), and eight herbs added group (BG-E8, BG-D8). Osteoblast proliferation, mineralization and calcium uptake activity of MG-63 cells were measured and tartrate resistant acid phosphatase activity of osteoclasts was analyzed. Results: Black goat meat had remarkably low fat and high level of calcium. Glutamic acid was the most abundant amino acid. Herbs added extract groups (BG-E6 and BG-E8) showed increased MG-63 cell proliferation in a concentration dependent manner, while all the distillates did not show the effect. All extracts and distillates showed significantly increased osteoblast mineralization depending on the concentration. In particular, herb added extract, BG-E6, increased 170.3% of control and the distillate of BG-D and BG-D6 increased up to 168.5% and 159.8%, respectively. Calcium uptake activities of all water extracts showed remarkable increase of BG-E6 and BG-E8 up to 615.5% and 628.1% of control, respectively. Ditillates had no effect except BG-D6. All water extracts significantly reduced the activity of tartrate-resistant acid phosphatase (TRAP) in osteoclasts derived from mouse bone marrow. Conclusion: Combination of black goat meat and medicinal herb increased the MG-63 cell proliferation and effectively inhibited osteoclast differentiation in both water extracts and distillate of them, which implies that they could be used as potent functional food materials for bone health.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.241-250
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• 2002

Background : Coal-worker's pneumoconiosis(CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in the alveolar spaces. CWP is usually divided into two stage : simple pneumoconiosis(SP) where there are a limited number of fibrotic lesions remain limited, with radiological opacities smaller than 1cm and progressive massive fibrosis(PMF), which is characterized by the development of a perifocal extensive fibrotic response of the lung and severe alterations in pulmonary function. In this study, the lymphocyte compartment and cytokine were evaluated by measuring the serum levels in the control, SP and PMF groups. Materials and Methods : The coal workers selected for this study were employees(patients?) of the Tae-Baek and Dong-Hae hospital. All were men, 45-76 years old and the mean duration of their exposure to coal dust was 23.2 years in the lymphocyte compartment and 24.3 years in the cytokine checked group. According to X-ray examination results, the patients were classified into either one of the SP, PMF categories. The normal controls examined were 26-70 years old men. The serum cytokine levels were estimated by using an end point enzyme immunoassay technique. Results : T lymphocyte, helper and suppressor T cells were highly related to pneumoconiosis in this study. A statistically significant decrease in the number of suppressor T lymphocytes was observed in the simple pneumoconiosis patients and at the same time, there was an increase in the lymphocyte index. Howevere, there was no statistically difference in the serum cytokines levels among the SP, PMF and control groups. Conclusion : T lymphocyte, helper T, and suppressor T cells may be highly related to the development of CWP compared to the control group particularly in the early stage of pneumoconiosis. The changes observed in the immunological system in patients with pneumoconiosis may lie at the bottom of the pathogenesis of fibrosis. Further study is needed to evaluate the lymphocyte compartment as a marker for pneumoconiosis development in the early stage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1249-1256
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• 2016

Black ginseng (BG) obtained by a 9-fold steaming process of Panax ginseng has been reported to have anti-oxidative, anti-obesity, and anti-diabetes effects. The current study evaluated the protective effect of BG by steaming time in an HCl/ethanol-induced acute gastritis model. BG was divided into four samples according to steaming-drying processing (Gin1, Gin3, Gin6, and BG). High performance liquid chromatography analysis, free radical scavenging activity, and total phenol and flavonoid contents were examined in ginseng and four BG samples. Compared with ginseng, BG showed a stronger radical scavenging effect and higher contents of total phenol and flavonoids. To evaluate the anti-gastritic effect of BG, mice were distributed into five groups: normal mice (N), acute gastritic mice with distilled water (CON), acute gastritic mice with 100 mg/kg of ginseng (Gin0), acute gastritic mice with 100 mg/kg of BG (BG), and acute gastritic mice with 10 mg/kg of sucralfate (SC). After 1 hour of pre-treatment with water, extracts (Gin0 and BG), or drug (SC), experimental groups except for N were orally administered 0.5 mL of 150 mM HCl/60% ethanol (v/v) mixture. Blood was collected 1 hour later from the heart, and gastric tissue was harvested. Reactive oxygen species (ROS) levels were measured in serum, and related protein expression was examined by Western blot assay. In HCl/ethanol-induced acute gastritic mice, treatment with ginseng or BG improved mucosal damage in the histological evaluation. The serum ROS level significantly decreased in the BG-treated group compared with the CON group. Furthermore, expression of inflammatory cytokines significantly decreased in the BG-treated group compared with the CON group. Based on these results, antioxidant and anti-gastritic activities of ginseng were enhanced by streaming-drying processing, in part due to an increase in biological active compounds.