• Applied Microscopy
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• v.39 no.2
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• pp.117-124
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• 2009

Clonorchis sinensis is the most important widely distributed parasite of the human bile duct in East Asia and the most prevalent parasitic helminth in Korea. The prevalence rate of human clonorchiasis has remained at about 2.9% in Korea. C. sinensis induces dilatation of the duct, hyperplasia of the mucosa, metaplasia or neoplasia of the mucosal epithelium, periductal inflammation and fibrosis, and thickening of the ductal wall. Fibroblast are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may also contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. In this study, ultrastructural changes, the distribution of lectin receptors and actin protein in cultured SD rat bile duct fibroblast after infection of C. sinensis were observed. Experimental group had been divided into four groups: normal bile duct fibroblast cultured in basal media (G1); C. sinensis infected bile duct fibroblast cultured in basal media (G2); normal bile duct fibroblast cultured in basal media containing excretory-secretory product (ESP) (G1-1); C. sinensis infected bile duct fibroblast cultured in basal media containing ESP (G2-1). Overall, once a host is infected by C. sinensis, it affects the host to the extent that sialic acid of ductal fibroblast is increased. Number of cytoplasmic process of SD rat bile duct fibroblast was increased. Actin protein and sialic acid were located in cell surface. Fibroblast induced by C. sinensis was not recovered to normal fibroblast. The cytoplasm bulk and cytoplasmic process were increased whereas the growth rate of the fibroblast of infected SD rat was reduced rather than that of normal fibroblast. In result, it inhibits fibroblast proliferation and increases actin protein on fibroblast cytoplasm, and so causes fibroblast metamorphosis and cellular mutation.

• Journal of Genetic Medicine
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• v.4 no.2
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• pp.186-189
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• 2007

More than 6,000 rare disorders including genetic diseases have been reported. Of them, 1,500 diseases (1,211 for clinical diagnosis and 289 for research only) are technically possible for genetic testing. In Korea, since 2005, only 63 genetic diseases is permitted for prenatal genetic testing by the "Bioethics and Biosafety Law". The article 25 in the law prescribes 63 genetic diseases without clear indication for its selection and inclusion criteria. In EU, USA, and other foreign countries, however, there is no provision in the statute on prenatal genetic testing; it is not restricted by a law. Recently, a woman (Mrs. L, 38y) who is a carrier for Menkes disease made an appeal to a government for an amendment of the "Bioethics and Biosafety Law" prohibiting the prenatal diagnosis of her pregnancy at risk for Menkes disease. Menkes disease (MNK) is an X-linked recessive disorder characterized by neurodegeneration, connective tissue defects and hair abnormalities, and no effective treatment is available yet. The prevalence rate of MNK is one in about 250,000 live births. Menkes syndrome patients fail to absorb copper from the gastrointestinal tract in quantities adequate for meeting nutritional needs. These needs seem particularly acute during the initial 12 month of life, when the velocity of brain growth and motor neurodevelopment. Most of pts. die around 3yrs. of age. Mrs. L had a boy with Menkes disease who died at 2y.o. in 2001. Subsequent pregnancy in 2003, she was able to have prenatal genetic testing for mutation of the Menkes (ATP7A) gene and delivered a healthy baby boy. Now, She is pregnant again and wants to have prenatal diagnosis. however, this time, she was not allowed to have any more because Menkes disease is not included in 63 genetic diseases permitted by the law for prenatal genetic testing, in spite of the fact that she is a Menkes disease carrier and her pregnancy is at risk to have an affected baby. This case shows the practical problem of the legal restriction for prenatal genetic testing in Korea. In this study, we report a arguable case and discuss the controversial issues in the legal restriction for prenatal genetic testing in Korea.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.439-444
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• 2004

UV irradiation produces free radicals and related reactive oxygen species (ROS), and these are injury to all most of organisms of skin cells and extracellular matrix (ECM). In addition, free radicals and ROS stimulate the overexpression of matrix metalloproteinases (MMPs) that can degrade most components of ECM such as collagen. Since collagen constitutes almost of skin connective tissue, their disarrangement causes wrinkle formation and droop of skin. Therefore, scavenging activity on free radicals, ROS and suppression of MMP-1 is expected to prevent skin photoaging. In this study, to investigate the relationship between photoaging and Draconis sanguis, we examined the effects of antioxidant, in vitro MMP inhibition and expression of UVA-induced MMP-1 in human dermal fibroblasts. Draconis sanguis was found to show scavenging activities of radicals and ROS with the $IC_{50}$ values of $183{\;}{\mu}g/mL$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and $30{\;}{\mu}g/mL$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Draconis sunguis inhibited the activities of MMP-1 in a does-dependent manner and the $IC_{50}$ value calculated from semi-log plots was $200{\;}{\mu}g/mL$. Also, UVA induced MMP expression was reduced $74\%$ by treatment with Draconis sanguis, and MMP-1 mRNA expression was reduced in a dose-dependent manner. Therefore Draconis sanguis was able to significantly inhibit MMP expression in protein and mRNA level. All these results suggested that Draconis sanguis may act as an anti-photoaging agent by antioxidation and reducing UVA-induced MMP-1 production.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.195-208
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• 1999

Background: Pulmonary infiltrate in immunocompromised hosts has many infectious and non-infectios etiologies. To evaluate the diagnostic yield and therapeutic implication of two invasive diagnostic methods, such as bronchoscopy and surgical lung biopsy, we performed retrospective analysis of these patients. Methods: All immunocompromised patients admitted to Samsung Medical Center from October 1995 to August 1998 who underwent bronchoscopy and/or surgical lung biopsy for the diagnosis of pulmonary infiltrates were included in this study. Confirmative diagnostic yield, the rate of changed therapeutic plan and patients' survival were investigated. Results: Seventy-five episodes of pulmonary infiltrates developed in 70 patients(M : F=46 : 24, median age 51). Underlying diseases of patients were hematologic malignancy(n=30), organ transplantation(n=11), solid tumor(n= 12), connective tissue disease(n=6) and others. Confirmative diagnosis was made in total 53 cases (70.7%), of which 70.2% had infectious etiology. Diagnostic yields of bronchoscopy, bronchoalveolar lavage(BAL), transbronchiallung biopsy(TBLB) and surgical lung biopsy were 35.0%(21/60), 31.4%(16/51), 25.0%(9/36) and 80.0%(20/25). Therapeutic plan was changed in 40%(24/60) of patients after bronchoscopy and in 36%(9/25) of patients after surgical lung biopsy. More patients survived (84.4% vs 60.5%, p=0.024) when therapeutic plan was changed after invasive diagnostic study. Conclusion: Bronchoscopy and surgical lung biopsy are helpful for the therapeutic implication of pulmonary infiltrates in immunocompromised hosts. Large-scale prospective case-control study may further clarify their limitation and usefulness.

• Journal of Veterinary Clinics
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• v.29 no.4
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• pp.283-296
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• 2012

Allergic contact dermatitis (ACD) is an inflammatory skin disease and regarded as a prototype of T-cell mediated delayed-type hypersensitivity reactions. Poly-${\gamma}$-glutamic acid (PGA) is a biodegradable polymer that is produced by Bacillus subtilis. This study was performed to assess the effects of PGA in a canine model of ACD. ACD was induced on the back of dogs induced by sensitization and repeated application by 2,4-dinitro-1-chlorobenzene (DNCB). Topical treatment of PGA was applied once a day for 12 days and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, skin pH, skin thickness and erythema index, were measured every two days during experimental periods. Histopathology and immunohistochemistry were performed to evaluate the antiinflammatory effect. In skin biophysical parameters, TEWL, skin hydration, skin thickness and erythema index were significantly increased, with a maximum increase appeared on day 2 (p < 0.05). On the other hand, skin pH was significantly decreased, with a maximum decrease appeared on day 2 (p < 0.01). After the completion of PGA treatment, skin biophysical parameters were significantly reached those of baseline in a time-dependent manner (p < 0.05). In histopathology, marked increases of epidermal thicknesses were induced after DNCB challenge with numerous inflammatory cell infiltrations and edematous changes, decreases of connective tissue occupied regions in dermis. In addition, marked increases of cytokine - tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$)-immunoreactivities in the dermis and of apoptotic markers - caspase-3 and PARP-immunoreactivities in the epidermis were observed in DNCB-PBS control as compared with intact control, respectively (p < 0.01). It means, the ACD and related apoptotic changes were induced by DNCB in the present study. However, these ACD induced by DNCB and related apoptosis in epidermis were significantly inhibited by treatment of PGA treated skin, the decreases of infiltrated inflammatory cells and related decreases of pro-inflammatory cytokine immunoreactivities were also observed (p < 0.01). Based on these findings, PGA may have anti-inflammatory and alleviatory effects in the allergic contact dermatitis.

• Journal of Veterinary Clinics
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• v.30 no.5
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• pp.339-345
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• 2013

Mitogen-activated protein kinases (MAPKs) are a family of central signaling molecules that respond to numerous stimuli and are known to participate in processes of cell survival and death. However, it is not clear on data for cell-type specific activation of MAPKs in the progression of gastric ulcer. In the present study, we assessed how MAPKs localized at various cell types during the progression of gastric ulcer induced by ibuprofen. Gastric ulcer was induced by the repeated treatment of 200 mg/kg ibuprofen with 8 hrs interval in a day. Animals were sacrificed at 24 hrs, 48 hrs, and 72 hrs after oral treatment of ibuprofen and gastric tissues were subjected to immunohistochemical and immunoblotting evaluation. Immunoreactivity of phospho-extracellular signal-regulated kinase (p-ERK) was mainly expressed at the proliferating zone of gastric mucosa in control rats. But, these signals for p-ERK were highly shifted from cells of proliferating zone to parietal cells of the basal regions 24 hrs after treatment of ibuprofen. p-ERK signal was strongly expressed in epithelial cells adjacent to ulcer margin and new capillary and infiltrated inflammatory cells within granulation tissue of the ulcer base above 48 hrs after treatment of ibuprofen. While, phospho-c-Jun $NH_2$ terminal kinase (p-JNK) was mainly localized to the nuclei of the surface epithelial cells and the glandular epithelial cells in early gastric injury. Also, p-JNK was often observed as a scattered pattern in different regions of gastric mucosa with early gastric injury. Gradually, signal of p-JNK was strongly stained in infiltrated inflammatory cells and fibroblasts within severe ulcer base. Phospho-p38 (p-p38) MAPK was observed as scattered pattern within connective tissues of gastric mucosa. Especially, p-p38 MAPK showed strong signal in infiltrated macrophages within ulcer base. These results show that each MAPK has a specific role in various cell types during the progression of gastric ulcer.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.619-634
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• 2002

Background : Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods : Eighteen Sprague-Dawley rats were divided into three groups: low tidal Volume (LVT, 7mL/Kg tidal volume, 3 $cmH_2O$ PEEP, 40/min), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 $IgG_1$. Results : In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was $4.70{\pm}0.14$, $6.82{\pm}1.28$ and $4.92{\pm}0.98$, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was $3.25{\pm}1.17$, $12.83{\pm}1.17$ and $4.67{\pm}0.52$, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was $3.33{\pm}2.07$, $12.17{\pm}2.79$ and $3.60{\pm}1.95$, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion : VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

• Journal of Yeungnam Medical Science
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• v.24 no.1
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• pp.24-40
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• 2007

Background : Accumulating evidence shows that interleukin(IL)-1 plays a critical role in inflammation and connective tissue destruction observed in both osteoarthritis and rheumatoid arthritis. IL-1 induces gene expression related to cytokines, chemokines and matrix metalloproteinases by activation of many different transcription factors. Materials and Methods : The chondrosarcoma cell line, SW1353, is known to be a valuable in vitro system for investigating catabolic gene regulation by IL-$1{\beta}$ in chondrocytic cells. To explore and analyze the changes in gene expression by IL-1 responsible for arthritis, SW1353 was treated with IL-1 for 1, 6 and 24 h and then total RNAs were purified for each time. The changes in gene expression were analyzed with 17k human cDNA microarrays and validated by semi-quantitative RT-PCR. Results : Greater than a two-fold change was observed in 1,200 genes including metallothioneins, matrix metalloproteinases, extracellular matrix proteins, antioxidant proteins, cytoskeleton proteins, cell cycle regulatory proteins, proteins for cell growth and apoptosis, signaling proteins and transcription factors. These changes appeared to be correlate with the pathophysiological changes observed in early osteoarthritis. Conclusion : cDNA microarray analysis revealed a marked variability in gene expression, and provided insight into the overall molecular changes. The result of this study provide initial information for further studies to identify therapeutic targets in osteoarthritis pathogenesis.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.15 no.3
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• pp.241-250
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• 1982

The structure of gonads, gametogenesis and reproductive cycle of the cockle, Fulvia mutice, were studied mainly by histological observation. The materials were monthly sampled in the southern area of Yeosu from October 1980 to September 1981. F. mutica was monoecious. The gonads were situated between the liver tissues and the outer fibronuscular layers compacted by the connective tissue fibers and muscle fibers beneath the outermost layer of simple cuboidal epithelium. The gonad was composed of a number of the ovarian sacs and the testicular tubules which form the tubular structure. Testicular tubules in the mature stage sometimes contained 'testis-ova' The undifferentiated mesenchymal tissues and the eosinophilic cells were abundantly distributed on the germinal epithelium in the early development stage. With the further development of the ovary and testis, these tissues and cells gradually disapprared. The undifferentiated mesenchymal tissues and the eosinophilic cells are related to the growing of the oocytes and spermatocytes . Early multiplicating oogonium was about $10{\mu}m$ in diameter. As the oocytes grow to $27-34\times50-58{\mu}m$ by increasing cytoplasm, the oocytes connected to the basement membrane by their egg-stalks. The ripe eggs were about $60{\mu}m$ in diameter and they were surrounded by gelatinous membrane. Most male germ cells in mature stage were transformed into the spermatozoa and they formed the sperm bundles. After spawning, undischarged ripe eggs and spermatozoa remained in the ovarian sac and the testicular tubule respectively for some time, then they finally degenerated. Especially the early spent ovarian sacs in May did not contract significantly and then they took part in the secondary maturation within two or three months during the summer season. The monthly changes of the fatness well agreed with the reproductive cycle. The reproductive cycle of F. mutica could be classified into six successive stages : multiplicative, growing, mature, spent, degenerative and recovery stage. It seems that the spawning season is closely rotated to the water temperature, and the spawning occurs from May to October at about $20^{\circ}C$ in water temperature. The peak spawning seasons appeared twice a year between June and July and in September. Acknowledgement The authors wish to express their gratitude to Dr. Kim, In Bae, Dr. Chun, Seh Kyu and Dr. Yoo, Sung Kyoo of National Fisheries University of Busan and Mr. Min, Byoung Seo of National fisheries Research and Development Agency for their critical reading of the manu script.

• The korean journal of orthodontics
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• v.23 no.2 s.41
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• pp.229-248
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• 1993

[ $Interferon-\gamma$ ] has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. $Interferon-\gamma$ slightly decreased $[^3H]thymidine$ incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-y whether it was determined by the $[^3H]proline$ incorporation rate or by the Lowry smethod. The effect of $interferon-\gamma$ on the individual protein was, however, differential, ie, it increased $[^3H]proline$ incorporation into the noncollagenous protein marginally, while it decreased $[^3H]proline$ incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of $interferon-\gamma$. The differential effects of the interferon-y on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. $Interferon-\gamma$ decreased steady state level of ${\alpha}1(I)$ procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the $interferon-\gamma$ induced collagen decrease in this cell, which meant prostaglandins were not involed in the process of $interferon-\gamma$ induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of $interferon-\gamma$ for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.