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Biomedical subjects

Sun Young Lee

Publications and source records attributed to Sun Young Lee.

At least 19 recordsLinked to original sources

Inhibitory effect of sesaminol glucosides on lipopolysaccharide-induced NF-kappaB activation and target gene expression in cultured rat astrocytes.

The inflammatory reaction plays an important role in the pathogenesis of the neurodegenerative disorder including Alzheimer's disease (AD). Sesame lignan compounds such as sesaminol glucosides (SG) exhibit a range of pharmacological activities including anti-oxidative and anti-inflammatory action. In this study, we tried to elucidate possible effects of SG on lipopolysaccharide (LPS)-induced inflammatory reaction and its underlying mechanism in cultured astrocytes. SG (10-100 microg/ml) inhibited LPS-induced generation of nitric oxide (NO) and reactive oxygen species (ROS), as well as inhibited LPS-induced cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression dose-dependently. This inhibitory effect of SG on NO and ROS generation was enforced by addition of glutathione (GSH) in culture. In addition, SG prevented LPS-induced DNA binding and transcriptional activity of nuclear factor KappaB (NF)-kappaB. Consistent with the inhibitory effect on NF-kappaB activity, SG inhibits phosphorylation and degradation of inhibitory KappaB (IkappaB), thereby translocation of p50 of NF-kappaB. These data show that SG has an anti-inflammatory effect through inhibition of NF-kappaB, and may be a useful agent for prevention of inflammatory disease like AD.

Analysis of Variance↗

A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies.

Over the last decade, gene expression microarrays have had a profound impact on biomedical research. The diversity of platforms and analytical methods available to researchers have made the comparison of data from multiple platforms challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and 'in-house' platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by quantitative real-time (QRT)-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent preprocessing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.

Chromosome Mapping↗

Differential expression profiling of genes in a complete hydatidiform mole using cDNA microarray analysis.

OBJECTIVES: To gain a better understanding of the genes involved in the pathogenesis of gestational trophoblastic diseases, we evaluated the genome-wide expression levels of genes in complete hydatidiform mole (H-mole) as compared to normal placenta using cDNA microarray technique. METHODS: The expression profiles of complete H-mole tissues were compared with those of normal placenta using cDNA microarray technique. The data obtained from 10,305 human genes were normalized by the print-tip-based LOWESS method. Significance analysis of microarray (SAM) was used to identify genes with statistically significant changes in expression. The expression levels of genes which showed significant differences between normal early placenta and complete H-mole tissues were further confirmed by RT-PCR. RESULTS: A cDNA microarray analysis consisting of 10,305 human genes revealed significant changes in the expression of 213 genes, with 91 genes being upregulated and 122 being downregulated. SAM revealed significant changes in gene expression, including those associated with signal transduction, cell structure, transcription, and apoptosis. Further RT-PCR analysis of altered gene expression in mole tissues supported the microarray analysis results. We confirmed the upregulation of TLE4, CAPZA1, PRSS25, RNF130, and USP1 in complete H-mole tissues. Moreover, our study provides the first evidence that ELK3, LAMA3, LNK, STAT2, and TNFRSF25 are downregulated in complete H-mole compared to normal early placenta tissues. CONCLUSIONS: These findings provide a large body of information regarding gene expression profiles associated with complete H-mole tumorigenesis and allow the identification of potential targets for tumor prevention or therapy.

DNA, Complementary↗

Purification and characterization of a heat-stable serine protease inhibitor from the tubers of new potato variety "Golden Valley".

Potide-G, a small (5578.9 Da) antimicrobial peptide, was isolated from potato tubers (Solanum tuberosum L. cv. Golden Valley) through extraction of the water-soluble fraction, dialysis, ultrafiltration and DEAE-cellulose and C18 reverse-phase high performance liquid chromatography. This antimicrobial peptide was heat-stable and almost completely suppressed the proteolytic activity of trypsin, chymotrypsin and papain, with no hemolytic activity. In addition, potide-G potently inhibited growth of a variety of bacterial (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Clavibacter michiganense subsp. michiganinse) and fungal (Candida albicans and Rhizoctonia solani) strains. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry revealed that the N-terminal sequence (residues from 1 to 11) of the protein is identical to that of potato proteinase inhibitor, a member of the Kunitz superfamily. And like other members of this class of protease inhibitor, potide-G may have a number of beneficial and therapeutic uses.

Amino Acid Sequence↗

Intravitreal triamcinolone acetonide in eyes with recurrent postvitrectomy diabetic vitreous hemorrhage.

PURPOSE: To evaluate the efficacy of intravitreal triamcinolone acetonide (IVT) for the management of recurrent post-vitrectomy diabetic vitreous hemorrhage (VH). DESIGN: Interventional case series. METHODS: Five eyes of five patients with recurrent postvitrectomy diabetic VH done more than three times where the common standard treatments has failed were administered 4 mg (0.1 ml) of triamcinolone acetonide ophthalmic suspension. The efficacy of IVT injection was assessed on day one; weeks one, two, and four; and months two and three. RESULTS: The visual acuity (VA) at the time of IVT injection ranged from hand motion (HM) to counting fingers (CF). Of the five eyes, four eyes experienced clearing of VH on seven, four, one, and one week after IVT injection with visible triamcinolone precipitates with blood clot in the inferior aspect of fundus. Of these four eyes, two eyes had visual improvement with 20/50 and 20/200, whereas two eyes developed recurrent VH. VH was not cleared in one eye, which required surgical procedure. CONCLUSIONS: IVT injection may be beneficial for clearing recurrent post-vitrectomy VH, possibly by mechanical sedimentation of triamcinolone with retained blood clot.

Aged↗

Mitomycin C, ceramide, and 5-fluorouracil inhibit corneal haze and apoptosis after PRK.

PURPOSE: To investigate the effects of mitomycin C (MMC), ceramide, and 5-fluororacil (5-FU) on haze after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UVB) radiation. METHODS: The right eyes of 42 New Zealand white rabbits were treated with PRK to correct -10 diopter with a 5-mm optical zone. Sponges soaked in 0.02% MMC, 10 or 40 micromol/L ceramide, or 0.5% 5-FU were applied to the right eyes of 6 rabbits each, and a tarsorrhaphy was performed. Eight weeks after complete healing, topical 0.02% MMC or 0.5% 5-FU was applied twice daily to the right eyes of 6 rabbits that had previously received PRK but no topical medication. The control group of 6 rabbits was treated only with PRK. Three weeks after PRK, all the laser-treated eyes were exposed to 100 mJ/cm UVB radiation. Corneal haze was assessed biomicroscopically every 2 weeks using the Fantes scale. Eyes were enucleated 2, 7, and 13 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with Apostain. RESULTS: Corneal haze was observed in all rabbits after PRK and was aggravated by UVB irradiation. When applied immediately after PRK, MMC induced corneal opacity and apoptosis of keratocytes, but, at later times, this reagent significantly suppressed opacity, Apostain-positive keratocytes and reactivation of keratocytes, even after UVB irradiation. In contrast, ceramide and 5-FU suppressed corneal opacity after PRK, but this effect was not sustained after UVB irradiation. CONCLUSIONS: MMC is a potent inhibitor of haze induced by PRK and UVB irradiation. Throughout the process of corneal wound healing, the severity of apoptosis and reactivation of keratocytes was closely correlated with haze formation.

Animals↗

Comparison of anthropometric data between end-stage renal disease patients undergoing hemodialysis and healthy adults in Korea.

Protein-calorie malnutrition is prevalent in hemodialysis (HD) patients. The prevalence of obesity in healthy Korean adults has increased rapidly during the last 10 years. However, there are few large scale data collections available about the current weight status of Korean HD patients. The weight statuses of 10,304 HD patients (data from the Insan Memorial Dialysis Registry 2002, Korean Society of Nephrology) were compared to those of 12,436 control subjects (age > 18) by using body mass index (BMI). Weight status was assessed by WHO classification for Asian-Pacific region [underweight (UW): < 18.5; normal weight (NW): 18.5-22.9; overweight (OW): 23-24.9; obese (OB): 25-29.9; and extremely obese (EOB): > 30 kg/m2] in both the control and HD patients. HD patients had significantly lower body weight and BMI than the controls in all age groups and in both sexes. For the male controls, the proportions of OW and OB showed a reversed U-shape, peaking at the 5th and 6th decades. of the numbers of those classified as NW and UW were relatively small. For the female controls, the proportions of OW and OB progressively increased with age. On the contrary, in HD patients, the proportions of NW and UW were large, up to more than 70%, and those of OW and OB were small in both sexes. In each age group, UW was seen significantly more in the HD group than in the control group. The 6th decade age group showed the highest prevalence ratio for UW in the HD group for both sexes, compared to the controls (Male: 17.33, Female: 17.68). The percentages of UW were related to HD duration and age in both sexes. In conclusion, Korean HD patients seem to have small proportions of OW and OB, compared to the general population, and protein-calorie malnutrition may still be an important nutritional condition.

Adult↗

Inhibitory effect of green tea extract on beta-amyloid-induced PC12 cell death by inhibition of the activation of NF-kappaB and ERK/p38 MAP kinase pathway through antioxidant mechanisms.

Beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Several lines of evidence support that Abeta-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Thus, agents that scavenge ROS level may usefully impede the development or progress of AD. Green tea extract has been known to have such antioxidant properties. Our previous studies demonstrate that green tea extract protected ischemia/reperfusion-induced brain cell death by scavenging oxidative damages of macromolecules. In this study, we investigated the effects of green tea extract on Abeta-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with Abeta25-35 (10-50 microM) showed intracellular ROS elevation, the formation of 8-oxodG (an oxidized form of DNA), and underwent apoptotic cell death in a dose-dependent manner. Abeta(25-35) treatment upregulated pro-apoptotic p53 at the gene level, and Bax and caspase-3 at the protein level, but downregulated anti-apoptotic Bcl-2 protein. Interestingly, co-treated green tea extract (10-50 microg/ml) dose-dependently attenuated Abeta(25-35) (50 microM)-induced cell death, intracellular ROS levels, and 8-oxodG formation, in addition to p53, Bax, and caspase-3 expression, but upregulated Bcl-2. Furthermore, green tea extract prevented the Abeta(25-35)-induced activations of the NF-kappaB and ERK and p38 MAP kinase pathways. Our study suggests that green tea extract may usefully prevent or retard the development and progression of AD.

Amyloid beta-Peptides↗

Transcriptional profiling in mouse skeletal muscle following a single bout of voluntary running: evidence of increased cell proliferation.

Skeletal muscle undergoes adaptation following repetitive bouts of exercise. We hypothesize that transcriptional reprogramming and cellular remodeling start in the early phase of long-term training and play an important role in skeletal muscle adaptation. The aim of this study was to define the global mRNA expression in mouse plantaris muscle during (run for 3 and 12 h) and after (3, 6, 12, and 24 h postexercise) a single bout of voluntary running and compare it with that after long-term training (4 wk of running). Among 15,832 gene elements surveyed in a high-density cDNA microarray analysis, 900 showed more than twofold changes at one or more time points. K-means clustering and cumulative hypergeometric probability distribution analyses revealed a significant enrichment of genes involved in defense, cell cycle, cell adhesion and motility, signal transduction, and apoptosis, with induced expression patterns sharing similar patterns with that of peroxisome proliferator activator receptor-gamma coactivator-1alpha and vascular endothelial growth factor A. We focused on the finding of a delayed (at 24 h postexercise) induction of mRNA expression of cell cycle genes origin recognition complex 1, cyclin A2, and cell division 2 homolog A (Schizoccharomyces pombe) and confirmed increased cell proliferation by in vivo 5-bromo-2'-deoxyuridine labeling following voluntary running. X-ray irradiation of the hindlimb significantly diminished exercise-induced 5-bromo-2'-deoxyuridine incorporation. These findings suggest that a single bout of voluntary running activates the transcriptional network and promotes adaptive processes in skeletal muscle, including cell proliferation.

Animals↗

Decrease in NF-kappaB, AP-1 and SP-1 activities in neuronal cells expressing presenilin 2.

Decreases in activities of the NF-kappaB, AP-1 and SP-1 transcription factors, which could act as antiapoptotic factors, in the presenilin 2 transfected PC12 cells, either in nontreatment conditions or under apoptotic stimulation, were found in this study. Similar results were also found in mice brain cells carrying presenilin 2, especially in the mutant gene expressed ones. These findings suggested that presenilin 2 may be implicated in neuronal cell death by altering the antiapoptotic activity of the transcription factors.

Animals↗

Inhibitory effect of 2'-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-kappa B activation in RAW 264.7 cells.

Cinnamomum cassia has been widely used for treating dyspepsia, gastritis, and inflammatory disease. In the present study, several of cinnamaldehyde derivatives were synthesized from various cinnamic acid based on the 2'-hydroxycinnamaldehyde isolated from the bark C. cassia Blume was investigated to compare their NO production and NF-kappa B activity from Raw 264.7 cell since nitric oxide (NO) and NF-kappa B have been shown to be implicated factors in the inflammatory disease. The results show that HCA, among the derivatives, most significantly inhibited lipopolysaccharide (LPS)-induced NO production and NF-kappa B transcriptional activity in a dose-dependent manner with an IC(50) value of 8 and 22 microM, respectively. We next investigated putative possible mechanisms of inhibitory effect of HCA on NO production. The inhibition of NO by HCA was consistent with the inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) expression. Moreover, HCA inhibited LPS-induced p50 and p65 translocation resulting in the inhibition of the DNA binding activity of the NF-kappa B, a central regulator of iNOS. The present results provided evidence that HCA, among cinnamaledhyde derivatives, has the most inhibitory effect on NO production through inhibition of NF-kappa B activation, and thus can be used as an anti-inflammatory agent.

Acrolein↗

Effect of sesaminol glucosides on beta-amyloid-induced PC12 cell death through antioxidant mechanisms.

Several lines of evidence support that beta-amyloid (Abeta)-induced neurotoxicity is mediated through the generation of reactive oxygen species (ROS) and elevation of intracellular calcium. In this study, we have investigated protective effects of sesaminol glucosides on Abeta-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. Sesaminol glucoside (50-250microg/ml) decreased Abeta(25-35)-induced ROS generation, formation of 8-oxodG, a form of oxidative DNA and elevation of intracellular calcium level concomitant with prevention of apoptotic cell death dose dependently. Sesaminol glucoside (50-250microg/ml) also effectively decreased Abeta1-42 and ADDL form of Abeta1-42 as well as the combination of H2O2 with FeSO4-induced cell damages. In mechanistic study, sesaminol glucosides attenuated Abeta25-35-induced activation of redox transcription factor nuclear factor-kappaB NF-kappaB through inhibition of p50 translocation and IkappaB phosphorylation, and blocked NF-kappaB-dependent luciferase activity in addition to the inhibitory effect on Abeta25-35-induced activation of ERK kinase signal pathway. Consistent with the inhibitory effect on Abeta25-35-induced stress-induced cell death, sesaminol glucosides decreased expression of pro-apoptotic gene p53, and Bax and caspase-3, but enhanced expression of anti-apoptotic Bcl-2. Moreover, the protective effects of sesaminol glucoside on Abeta25-35-induced ROS generation, NF-kappaB activation and cell death were further enhanced with glutathione. This study therefore suggests that sesaminol glucosides have protective effect on Abeta-induced neuronal cell death, and its effect may be through antioxidative property.

8-Hydroxy-2'-Deoxyguanosine↗

WHO class-specific equations using height for predicting body weight: crude indicator for dry weight in haemodialysis patients.

AIM: Body weight (BW) might be related to total body water, and the difference between a patient's actual BW and ideal BW (IBW) might be the volume marker. However, there has been no information about the association between IBW and dry weight (DW) in haemodialysis (HD) patients. METHODS: First, we analysed the relationship between DW and IBW in 51 HD patients. The IBW was calculated by 21 x Height (Ht)(2). Weight status was analysed by the WHO classification. Second, in 12 436 controls, linear equations using Ht(2) were sought to predict the BW in each sex and WHO class. Third, using these equations, predicted BW (PW) was compared with DW in each WHO class at the initiation and after 1 year in 619 new HD patients, retrospectively. RESULTS: Among 51 HD patients, 38 were normal weight in whom there was no difference between DW and IBW. In each sex and WHO class of the 12 436 controls, linear equations using Ht(2) were developed to predict BW. These equations were applied to 619 new HD patients. In males, there were no differences between PW and DW in underweight (UW), overweight (OW), obese (OB) and extremely obese (EOB) patients at the initiation of the HD. In females, there were no differences between PW and DW in OW patients. Despite no statistical differences, there were wide ranges of distribution from -6 to 6 kg between PW and DW. CONCLUSIONS: BW had a linear relationship with Ht(2) and might be predictable by the WHO class-specific equation using Ht(2). These equations might be useful as a crude indicator of DW in HD patients.

Adult↗

Overlapping gene mutations of hepatitis B virus in a chronic hepatitis B patient with hepatitis B surface antigen loss during lamivudine therapy.

Disappearance of hepatitis B surface antigens (HBsAg) in chronic hepatitis B usually indicates clearance of hepatitis B virus (HBV) infection. However, false HBsAg negativity with mutations in pre-S2 and 'a' determinant has been reported. It is also known that YMDD mutations decrease the production of HBV and escape detection of serum HBsAg. Here, we report overlapping gene mutations in a patient with HBsAg loss during the lamivudine therapy. After 36 months of lamivudine therapy in a 44-yrold Korean chronic hepatitis B patient, serum HBsAg turned negative while HBV DNA remained positive by a DNA probe method. Nucleotide sequence of serum HBV DNA was compared with the HBV genotype C subtype adr registered in NCBI AF 286594. Deletion of nucleotides 23 to 55 (amino acids 12 to 22) was identified in the pre-S2 region. Sequencing of the 'a' determinant revealed amino acid substitutions as I126S, T131N, M133T, and S136Y. Methionine of rtM204 in the P gene was substituted for isoleucine indicating YIDD mutation (rtM204I). We identified a HBV mutant composed of pre-S2 deletions and 'a' determinant substitutions with YMDD mutation. Our result suggests that false HBsAg negativity can be induced by combination of overlapping gene mutations during the lamivudine therapy.

Adult↗

Development of anthropometry-based equations for the estimation of the total body water in Koreans.

For developing race-specific anthropometry-based total body water (TBW) equations, we measured TBW using bioelectrical impedance analysis (TBW(BIA)) in 2,943 healthy Korean adults. Among them, 2,223 were used as a reference group. Two equations (TBW(K1) and TBW(K2)) were developed based on age, sex, height, and body weight. The adjusted R2 was 0.908 for TBW(K1) and 0.910 for TBW(K2). The remaining 720 subjects were used for the validation of our results. Watson (TBW(W)) and Hume-Weyers (TBW(H)) formulas were also used. In men, TBW(BIA) showed the highest correlation with TBW(H), followed by TBW(K1), TBW(K2) and TBW(W). TBW(K1) and TBW(K2) showed the lower root mean square errors (RMSE) and mean prediction errors (ME) than TBW(W) and TBW(H). On the Bland-Altman plot, the correlations between the differences and means were smaller for TBW(K2) than for TBW(K1). On the contrary, TBW(BIA) showed the highest correlation with TBW(W), followed by TBW(K2), TBW(K1), and TBW(H) in females. RMSE was smallest in TBW(W), followed by TBW(K2), TBW(K1) and TBW(H). ME was closest to zero for TBW(K2), followed by TBW(K1), TBW(W) and TBW(H). The correlation coefficients between the means and differences were highest in TBW(W), and lowest in TBW(K2). In conclusion, TBW(K2) provides better accuracy with a smaller bias than the TBW(W) or TBW(H) in males. TBW(K2) shows a similar accuracy, but with a smaller bias than TBW(W) in females.

Adult↗

[Expression of hedgehog proteins in periampullary cancer].

BACKGROUND/AIMS: Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma. METHODS: We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained: <5%, weakly stained: 5-50%, and strongly stained: >50%). RESULTS: All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p<0.001). CONCLUSIONS: Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.

Adenocarcinoma↗

Analysis of the major patterns of B cell gene expression changes in response to short-term stimulation with 33 single ligands.

We examined the major patterns of changes in gene expression in mouse splenic B cells in response to stimulation with 33 single ligands for 0.5, 1, 2, and 4 h. We found that ligands known to directly induce or costimulate proliferation, namely, anti-IgM (anti-Ig), anti-CD40 (CD40L), LPS, and, to a lesser extent, IL-4 and CpG-oligodeoxynucleotide (CpG), induced significant expression changes in a large number of genes. The remaining 28 single ligands produced changes in relatively few genes, even though they elicited measurable elevations in intracellular Ca(2+) and cAMP concentration and/or protein phosphorylation, including cytokines, chemokines, and other ligands that interact with G protein-coupled receptors. A detailed comparison of gene expression responses to anti-Ig, CD40L, LPS, IL-4, and CpG indicates that while many genes had similar temporal patterns of change in expression in response to these ligands, subsets of genes showed unique expression patterns in response to IL-4, anti-Ig, and CD40L.

Animals↗