• Journal of Life Science
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• v.18 no.12
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• pp.1657-1664
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• 2008

We determined the prevalence of human papillomavirus (HPV) by DNA chip test in 549 women and cytologic diagnosis. 237 of 549 women (43.17%) subjected with HPV DNA Chip examination were found positive for HPV. 210 (88.60%, High group) were infected with high-risk HPV types. 17 (7.17%, Low group) were infected with low-risk HPV types (6, 11, 40, 44, 70) and 17 (7.17%, Mixed group) were infected with mixed types. According to age, in their twenties, thirties, forties, fifties and over sixties, the prevalence of infection with high-risk HPV types were 1.26% (3/237), 15.61% (37/237), 31.65% (75/237), 23.21% (55/237), and 13.92% (33/237), respectively. In the Low and Mixed group, percentages of infection with HPV were significantly lower than that of the High group. On the comparison of cytologic diagnosis (224 women) by Pap smear and DNA chip positive (237 women) for HPV, 132 out of 194 cases in the High group (68.04%) suffered cervical lesions with ASCUS (atypical squamous cells of undetermined significance, 7.22%), LSIL (low grade squamous intraepithelial lesion, 15.98%), HSIL (high grade SIL, 23.20%) and ICC (invasive cervical cancer, 21.65%). The Low group (14/224 women) showed 1 case of ASCUS and 6 cases of LSIL, whereas the Mixed group (4/224 women) had only 2 cases of ASCUS. According to the HPV subtypes, the high-risk types 16 and 18 induced 26 and 7 cases of ICC, respectively, whereas other HPV subtypes induced lower or no ICC incidence. In conclusion, the present data imply that the prevalence of HPV was 43.17%, high-risk HPV type 16 is a major factor, which causes precancerous and/or cervical cancer in woman and that HPV DNA chip is an accurate and useful tool for detecting HPV.

• Journal of Life Science
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• v.21 no.6
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• pp.796-804
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• 2011

Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

• Journal of Life Science
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• v.19 no.6
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• pp.770-780
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• 2009

A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

• Journal of Life Science
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• v.19 no.12
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• pp.1690-1697
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• 2009

CD11c and costimulatory molecules such as CD80 and CD86 express mainly in dendritic cells (DCs). In this study, we investigated the biologic effects of recombinant Fms-like tyrosine kinase-3 (Flt-3) ligand on the expression of DC surface markers, including CD11c in leukemia cell lines, such as KG-1, HL-60, NB4, and THP-1 cells. The expression of the Flt-3 receptor was found in NB4 and HL-60 cells, as well as KG-1 cells, but not in THP-1 cells. When KG-1 cells were cultured in a medium containing Flt-3 ligand or granulocyte macrophage-colony stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-$\alpha$, cell proliferation was inhibited and the expression levels of CD11c, major histocompatibility complex (MHC)-I, and MHC-II were increased in the cells. Flt-3 ligand also increased the expression level of CD11c on HL-60 and NB4 cells, but not on THP-1 cells. In comparison with CD11c expression, the expression level of CD11b on KG-1 cells, but not on NB4 and HL-60 cells, was slightly increased by Flt-3 ligand. Flt-3 ligand induced phosphorylation of extracellular signal-regulated kinase-1/2 (ERK-1/2) and p38-mitogen-activated protein kinase (p38-MAPK) in KG-1 cells, and the up-regulation of CD11c expression by Flt-3 ligand in the cells was abrogated by PD98059, an inhibitor of MEK. The results suggest that Flt-3 ligand up-regulates DC surface markers on $CD34^+$ myelomonocytic KG-1 cells, as well as promyelocytic leukemia cells, and that the differentiation of the leukemia cells into DC-like cells by Flt-3 ligand is mediated by ERK-1/2 activity.

• Journal of Life Science
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• v.24 no.12
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• pp.1276-1283
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• 2014

Cell adhesion molecules determine the cell-cell binding and the interactions between cells and extracellular signals. Cell-cell junctional complexes, which maintain the structural integrity of tissues, consist of more than 50 proteins including multi-PDZ domain protein 1 (MUPP1). MUPP1 contains 13 postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains and serves a scaffolding function for transmembrane proteins and cytoskeletal proteins or signaling proteins, but the mechanism how MUPP1 links and stabilizes the juxtamembrane proteins has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and cell adhesion molecule 1 (Cadm1, also known as SynCAM1, Necl-2, or TSLC1). Cadm1 bound to the second PDZ domain of MUPP1. The carboxyl (C)-terminal end of Cadm1 has a type II PDZ-association motif (-Y-F-I) which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. MUPP1 also bound to the C-terminal cytoplasmic tail region of other Cadm family members (Cadm2, Cadm3, and Cadm4). In addition, these protein-protein interactions were observed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti-MUPP1 antibody co-immunoprecipitated Cadm1 and Cadm4 with MUPP1 from mouse brain extracts. These results suggest that MUPP1 could mediate interaction between Cadms and cytoskeletal proteins.

• Journal of Life Science
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• v.26 no.12
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• pp.1376-1382
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• 2016

Xylitol is widely used in the food and medical industry. It is produced by the reduction of xylose (lignocellulosic biomass) in the Saccharomyces cerevisiae strain, which is considered genetically safe. In this study, the expression system of the GRE3 (YHR104W) gene that encodes xylose reductase was constructed to efficiently produce xylitol in the S. cerevisiae strain, and the secretory production of xylose reductase was investigated. To select a suitable promoter for the expression of the GRE3 gene, pGMF-GRE3 and pAMF-GRE3 plasmid with GAL10 promoter and ADH1 promoter, respectively, were constructed. The mating factor ${\alpha}$ ($MF{\alpha}$) signal sequence was also connected to each promoter for secretory production. Each plasmid was transformed into S. cerevisiae $SEY2102{\Delta}trp1$, and $SEY2102{\Delta}trp1$/pGMF- GRE3 and $SEY2102{\Delta}trp1$/pAMF-GRE3 transformants were selected. In the $SEY2102{\Delta}trp1$/pGMF-GRE3 strain, the total activity of xylose reductase reached 0.34 unit/mg-protein when NADPH was used as a cofactor; this activity was 1.5 fold higher than that in $SEY2102{\Delta}trp1$/pAMF-GRE3 with ADH1 as the promoter. The secretion efficiency was 91% in both strains, indicating that most of the recombinant xylose reductase was efficiently secreted in the extracellular fraction. In a baffled flask culture of the $SEY2102{\Delta}trp1$/pGMF-GRE3 strain, 12.1 g/l of xylitol was produced from 20 g/l of xylose, and ~83% of the consumed xylose was reduced to xylitol.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.169-175
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• 2005

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. $Amyloid-\beta$ deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on $amyloid-\beta-peptide-mediated$ cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to $Amyloid-\beta$ resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of $amyloid-\beta$ was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in $amyloid-\beta-treated$ C6 cells without alteration of anti-apoptotic Bcl-2 and $Bcl-X_L$ expression. However, pre-treatment of resveratrol significantly inhibited $amyloid-\beta-induced$ p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against $amyloid-\beta-induced$ cytotoxicity by promoting the survival of glial cells.

• Pediatric Infection and Vaccine
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• v.9 no.2
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• pp.182-192
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• 2002

Purpose : This study was performed to characterize the epidemiologic and clinical features of acute adenoviral lower respiratory tract infections(LRTIs). Methods : Virological analysis was done from respiratory specimens obtained from patients with LRTIs hospitalized to other hospitals and referred to the Department of Pediatrics, Seoul National University Children's Hospital(SNUCH) from June 1998 to July 2000. Viral diagnosis was made by isolation of viruses employing HEp-2 cell culture and indirect immunofluorescent staining with monoclonal antibodies. Serotypes of adenoviruses were determined by neutralization test using antiserum for types 1, 2, 3, 4, 5, 6, 7 and 11. Medical records of children admitted to the SNUCH were reviewed retrospectively. Results : Adenovirus was isolated from 118(9.0%) of 1,305 children with LRTIs. Serotypes were 3(39.0%), 7(16.9%), 1(11.0%), 2(7.6%), 4(7.6%), 6(5.9%), 11(2.5%), and 5(0.8%) and 10 strains(8.5%) were not neutralized by antisera included in the study. Infections by type 3 and type 7 occurred in outbreaks. Male to female ratio was 1.0:0.9 and mean age was 1.95 years. The clinical diagnoses were pneumonia(83%), acute tracheobronchitis(12%) and bronchiolitis(5%). Associated symptoms, signs and abnormal laboratory findings included cough(100%), sputum(73.5%), fever(54.2%), rale(59.3%), wheezing(34%), anemia(35%) and leukopenia(15.8%). Mortality was in 13.5%. Residual radiologic sequelae was identified in 32.6% of the patients followed. Conclusion : These data confirms that adenovirus may cause severe lower respiratory tract diseases, and infections by type 3 and 7 may occured in outbreaks.

• Pediatric Infection and Vaccine
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• v.11 no.2
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• pp.183-191
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• 2004

Purpose : The purpose of this study was to compare the clinical features of staphylococcal scalded skin syndrome(SSSS) isolated methicillin-resistant Staphylococcal aureus(MRSA) with those of SSSS isolated methicillin-sensitive Staphylococcal aureus(MSSA) in children. Methods : We retrospectively reviewed the medical records and microbiological results of 36 cases of SSSS who were admitted to the Pediatric Department of Ulsan Dong-Kang General Hospital from Jan. 1999 to Dec. 2003. Results : Among 36 cases, there were 7 generalized types, 1 abortive type in MRSA group and 5 generalized types, 6 abortive types in MSSA group. The peak incidence of age was between 2 and 5 years in both groups. SSSS were diagnosed with increasing frequency. Most of MRSA group were diagnosed in 2003(6/8). The peak seasonal incidence was fall and winter in both groups. Facial lesion was observed in all cases followed by flexural lesion in both groups. Staphylococci were isolated from the skin and throat most frequently in both groups. Upper respiratory illness and conjunctivitis were most common preceding infections in both groups. Among 8 cases of MRSA group, 4 cases were treated completely with ampicillin-sulbactam. There was no significant difference of mean duration of admission between MRSA group and MSSA group. Conclusion : There was no significant difference of clinical features between MRSA group and MSSA group although generalized types of SSSS were more common in MRSA group than in MSSA group.

• Pediatric Infection and Vaccine
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• v.13 no.2
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• pp.137-146
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• 2006

Purpose : A regional lymphadenitis is the most frequent adverse reaction of BCG. In order to find out developmental factors and establish a strategy of management, we investigated the clinical courses of children with lymphadenitis following BCG on the aspect of BCG strains, suppurative rates according to the sizes of lymph node and the clinical difference with or without treatment. Methods : From January 1997 to June 2004, 52 children less than 24 month-age-old diagnosed as BCG lymphadenitis in Department of Pediatrics, St. Vincent's Hospital, The Catholic University of Korea were enrolled. The type of BCG strain, place of vaccination, location and size of lymphadenitis were assessed with medical records, retrospectively. Finally, we analysed the correlations between BCG strains or the sizes of lymph node and natural remission or suppuration. Results : The first detected mean age of BCG lymphadenitis was 5.5 month-age. The larger of the measurement was at the first visiting, the younger of age that was first presented. The most frequent location was the same sided axillary region of BCG injection. Among 52 subjects, 46 cases(88.5%) were vaccinated with intradermal Pastuer strain, and only 5 cases(9.6%) were done with percutaneous multipunctured Tokyo strain. Twenty eight cases(53.8%) were regressed naturally, otherwise 24 cases(46.2%) were suppurated. The larger those were sized, the higher freqeuncies those were suppurated on, significantly. Treatment with medications could not prevent the suppuration and could not shorten the healing periods. Conclusion : We predict that there are differences between the occurrent rate of BCG lymphadenitis and BCG strains or methods. Treatment with medication is not recommended owing to its ineffectiveness. Especially, in case of non-suppurative lymphadenitis should be onlyless influence on the tuberculin skin test, cause less adverse reactions, and is inexpensive. observed without treatment, because it could be regressed naturally. An ideal BCG makes a scar, We should make an effort to choose the best BCG strain that can fulfill such requirements.