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Biomedical subjects

Won Kim

Publications and source records attributed to Won Kim.

At least 19 recordsLinked to original sources
PubMed2006

Bile acid-mediated thrombospondin-1 induction in hepatocytes leads to transforming growth factor-beta-dependent hepatic stellate cell activation.

In cholestasis, bile acids induce hepatocyte apoptosis, while activation of hepatic stellate cells (HSCs) results in fibrosis. Since transforming growth factor-beta (TGF-beta) is a critical mediator in this process, we hypothesized that bile acids may participate in TGF-beta-mediated HSC activation in cholestasis. Bile acid treatment increased TGF-beta transcription in hepatocytes, while the total TGF-beta concentration in culture media rapidly decreased following bile acid treatment. Bile acid treatment promptly induced thrombospondin-1 expression in hepatocytes, which is a potent activator of latent TGF-beta, whereas this induction was not observed in bile acid-treated HSCs. HSCs co-cultured with hepatocytes showed a significantly higher level of Smad2 phosphorylation and collagen alpha1 synthesis following bile acid treatment than cells cultured without hepatocytes. Moreover, this enhanced collagen synthesis was significantly inhibited in the presence of TGF-beta receptor inhibitor. These observations imply that bile acids induce thrombospondin-1 expression in hepatocytes, which activates latent TGF-beta leading to HSC activation.

Bile Acids and Salts↗
PubMed2006

A delayed case of renal artery pseudoaneurysm presented with gross hematuria and azotemia in solitary kidney following percutaneous nephrostomy: treated by transcatheter coil embolization.

Renal arteriovenous fistula or pseudoaneurysms developing after invasive procedures are either asymptomatic or show only transient symptoms. We describe here a case of symptomatic renal artery pseudoaneurysm that presented with gross hematuria and azotemia. The pseudoaneurysm of renal artery was diagnosed by ultrasonography and abdominal magnetic resonance imaging (MRI), and it was successfully treated by percutaneous transcatheter coil embolization. A high index of suspicion is essential for the early diagnosis and treatment of delayed gross hematuria in patients with history of percutaneous nephrostomy.

Aged, 80 and over↗
PubMed2006

Renoprotective effect of COMP-angiopoietin-1 in db/db mice with type 2 diabetes.

BACKGROUND: Inflammatory processes have been recently seen as underlying the pathogenesis of diabetic nephropathy. Angiopoietin-1 (Ang1) plays essential roles in regulating vascular growth, development, maturation, permeability and inflammation. We have developed a soluble, stable and potent Ang1 variant, cartilage oligomeric matrix protein (COMP)-Ang1. METHODS: In this study, db/db mice were treated with recombinant adenovirus expressing either COMP-Ang1 or LacZ. Histology, inflammatory, metabolic, and fibrotic parameters and signalling pathway were evaluated. RESULTS: COMP-Ang1 reduced albuminuria and decreased mesangial expansion, thickening of the glomerular basement membrane and podocyte foot process broadening and effacement. COMP-Ang1 suppressed both renal expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 and monocyte/macrophage infiltration in diabetic db/db mice. COMP-Ang1 also reduced renal tissue levels of transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin, fibronectin, as well as Smad 2/3 expression, but increased Smad 7 expression. In human umbilical vein endothelial cells (HUVECs) grown in high glucose concentrations of glucose, recombinant COMP-Ang1 protein decreased nuclear factor-kappaB (NF-kappaB) expression. COMP-Ang1-mediated inhibition of increased NF-kappaB-DNA binding in nuclear extracts from HUVECs grown in high glucose was significantly blocked by soluble Tie2 receptor-Fc. In addition, COMP-Ang1 significantly decreased fasting blood glucose level, epididymal fat weight to body weight ratio, and epididymal adipocyte size in diabetic db/db mice. After intraperitoneal glucose challenge, COMP-Ang1 significantly lowered plasma glucose levels. However, there was no difference in serum insulin levels. CONCLUSION: We conclude that COMP-Ang1 delayed the fibrotic changes in the kidney of diabetic db/db mice through its anti-inflammatory or metabolic effects.

Animals↗
PubMed2006

Increased leptin and decreased ghrelin level after smoking cessation.

Smoking cessation is associated with transient increases in body weight. Leptin and ghrelin are known to be major mediators of appetite, weight and the reward pathway. Therefore, this study assessed the changes in the plasma leptin and ghrelin level and their relationship with the body weight and appetite after smoking cessation in the Korean population. Eighteen subjects, who had stopped smoking for 2 months were enrolled in this study. The body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR), weight and appetite were measured before and after smoking cessation. In addition, the plasma leptin and ghrelin levels were measured. The BMI, BFM, WHR, weight and appetite were significantly higher than baseline in those who had gave up smoking for 2 months (p<0.05). The plasma leptin concentration increased and the plasma ghrelin level decreased after smoking cessation. The change in the leptin level was positively correlated with the change in the body mass index and body fat mass. These results do not support the direct mediation of the leptin-ghrelin-neuropeptide Y (NPY) system on weight gain after smoking cessation. It appears that weight and appetite is regulated by a more complicated mechanism after smoking cessation.

Adult↗
PubMed2006

COMP-angiopoietin-1 ameliorates renal fibrosis in a unilateral ureteral obstruction model.

Injury to the renal microvasculature may be a major factor in the progression of renal disease; therefore, protection of endothelial cells (EC) in renal vasculature may have a therapeutic role in renal fibrosis. Recently, a soluble, stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, was developed. The contribution of COMP-Ang1 in renal interstitial fibrosis, however, remains to be clarified. This study investigated the effects of COMP-Ang1 on peritubular capillary EC in the renal cortex and the renal fibrogenic process that is triggered by unilateral ureteral obstruction. COMP-Ang1 preserved renal platelet-EC adhesion molecule-1-and Tie2-positive EC. Morphologic examination indicated less tubular injury and tubulointerstitial fibrosis in mice that received COMP-Ang1 than vehicle-treated mice. Interstitial type I collagen and myofibroblast accumulation were significantly suppressed by COMP-Ang1 treatment. COMP-Ang1 increased Tie2 and Akt phosphorylation in ureteral obstructed kidneys. Renal surface microvasculature and renal blood flow were higher after treatment with COMP-Ang1 than with vehicle. COMP-Ang1 treatment decreased monocyte/macrophage infiltration, tissue levels of TGF-beta1, and Smad 2/3 phosphorylation and increased Smad 7 in the obstructed kidney. These results demonstrate that COMP-Ang1 treatment can decrease the progression of renal fibrosis in unilateral ureteral obstruction. COMP-Ang1 may be an endothelium-specific therapeutic modality in fibrotic renal disease.

Angiopoietin-1↗
PubMed2006

Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population.

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population. 244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale--Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment. We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.

Age of Onset↗
PubMed2006

Using MEDLINE as a knowledge source for disambiguating abbreviations and acronyms in full-text biomedical journal articles.

Biomedical abbreviations and acronyms are widely used in biomedical literature. Since many of them represent important content in biomedical literature, information retrieval and extraction benefits from identifying the meanings of those terms. On the other hand, many abbreviations and acronyms are ambiguous, it would be important to map them to their full forms, which ultimately represent the meanings of the abbreviations. In this study, we present a semi-supervised method that applies MEDLINE as a knowledge source for disambiguating abbreviations and acronyms in full-text biomedical journal articles. We first automatically generated from the MEDLINE abstracts a dictionary of abbreviation-full pairs based on a rule-based system that maps abbreviations to full forms when full forms are defined in the abstracts. We then trained on the MEDLINE abstracts and predicted the full forms of abbreviations in full-text journal articles by applying supervised machine-learning algorithms in a semi-supervised fashion. We report up to 92% prediction precision and up to 91% coverage.

Artificial Intelligence↗
PubMed2006

Rosiglitazone ameliorates cisplatin-induced renal injury in mice.

BACKGROUND: Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Agonists of the peroxisome proliferator-activated receptor-gamma (PPARgamma), such as rosiglitazone, have been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to examine the protective effects of rosiglitazone on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. METHODS: Mice were treated with cisplatin with or without pre-treatment with rosiglitazone. Renal functions, histological findings, aquaporin 2 (AQP2) and adhesion molecule expression, macrophage infiltration and tumour necrosis factor-alpha (TNF-alpha) levels were investigated. The effect of rosiglitazone on nuclear factor (NF)-kappaB activity and on viability was examined using cultured human kidney (HK-2) cells. RESULTS: Rosiglitazone significantly decreased both the damage to renal function and histological pathology after cisplatin injection. Pre-treatment with rosiglitazone reduced the systemic levels of TNF-alpha and down-regulated adhesion molecule expression in addition to the infiltration of inflammatory cells after cisplatin administration. Rosiglitazone restored the decreased AQP2 expression after cisplatin treatment. Pre-treatment with rosiglitazone blocked the phosphorylation of the p65 subunit of NF-kappaB in cultured HK-2 cells. Rosiglitazone had a protective effect via a PPARgamma-dependent pathway in cisplatin-treated HK-2 cells. CONCLUSION: These results showed that pre-treatment with rosiglitazone attenuates cisplatin-induced renal damage through the suppression of TNF-alpha overproduction and NF-kappaB activation.

Anilides↗
PubMed2006

Protective role of L-2-oxothiazolidine-4-carboxylic acid in cisplatin-induced renal injury.

BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced nephrotoxicity. l-2-oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug, and increases cellular glutathione (GSH). OTC is converted to cysteine by the intracellular enzyme, oxoprolinase. To date, the protective role of OTC on cisplatin-induced renal injury has not been investigated. The purpose of the present study was to examine the protective effect of OTC on cisplatin-induced renal injury and to examine the mechanism of its protection. METHODS: Mice were treated with cisplatin with or without administration of OTC. The generation of reactive oxygen species (ROS), expression of intercellular adhesion molecule (ICAM)-1 and monocyte chemoattractant protein (MCP)-1 were determined in the kidney using 2',7'-dichlorofluorescein diacetate, immunostaining or western blot analysis. Nuclear factor (NF)-kappaB activity, infiltration of F4/80-positive cells and apoptosis were also investigated in addition to renal function and histology using electrophoretic mobility shift assay, immunostaining, western blot analysis, uridine triphosphate (dUTP) nick-end labelling or periodic acid-Schiff staining. The effect of OTC on superoxide dismutase activity and GSH level in cisplatin-treated normal adult human kidney (HK-2) cells were measured using assay kits. RESULTS: The administration of OTC resulted in a significant reduction of cisplatin-induced ROS production, the p65 subunit of NF-kappaB translocation into nucleus, expression of ICAM-1, caspase 3 activity, expression of MCP-1 and the infiltration of macrophages into renal tissue. OTC markedly ameliorated renal damage induced by cisplatin through antioxidant and anti-inflammatory effect. CONCLUSIONS: These results suggest that OTC can be a potential therapeutic agent in cisplatin-induced renal injury through decreasing the ROS levels and activation of NF-kappaB.

Animals↗
PubMed2006

Resveratrol suppresses tumor necrosis factor-alpha-induced fractalkine expression in endothelial cells.

Up-regulation of fractalkine is involved in vascular and tissue damage in inflammatory conditions. Resveratrol has been shown to have anti-inflammatory, antioxidant, and antitumor activities. Its regulatory effects on expression of fractalkine in vascular endothelial cells and fractalkine receptor CX3CR1 in monocytes have not been studied. We evaluated the effects of resveratrol on fractalkine expression in human umbilical vein endothelial cells and CX3CR1 expression in THP-1 cells in response to treatment with tumor necrosis factor (TNF)-alpha. TNF-alpha significantly induced fractalkine mRNA and protein expression in endothelial cells. Resveratrol strongly suppressed TNF-alpha-induced fractalkine expression in endothelial cells through suppression of nuclear factor-kappaB and Sp1 activities. Resveratrol decreased the number of TNF-alpha-induced fractalkine-positive endothelial cells and CX3CR1-positive cells determined by flow cytometric analysis. Resveratrol suppressed TNF-alpha-stimulated monocytes adhesion to human umbilical vein endothelial cells. Immunohistochemical analysis revealed that resveratrol suppressed TNF-alpha-induced arterial endothelial fractalkine expression in heart, kidney, and intestine and decreased ED-1-positive cell infiltration in intestinal villi. Resveratrol may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury in inflammatory conditions.

Animals↗
PubMed2006

Intraspecific molecular phylogeny, genetic variation and phylogeography of Reticulitermes speratus (Isoptera: Rhinotermitidae).

Population structure was investigated in Reticulitermes speratus populations in the Korean Peninsula and the Japanese Archipelago. All trees derived from analyses of the combined sequence dataset of two mitochondrial genes, COII and COIII, showed that R. speratus populations cluster into two major clades comprising the Korean/southern Japanese populations and the north-ern Japanese populations. Analysis of population ge-netic structure showed strong genetic partitioning between populations of the two clades. To understand historical migration routes and current distributions, the phylogeographic history of R. speratus was inferred from intra-/interspecific phylogeny and diver-gence times estimated between the clades of the phylogenetic tree. The estimated migration route and divergence time of ancestral R. speratus are congruent with recent paleogeographic hypotheses involving land-bridge connections between the Asian continent and the Japanese Archipelago. We suggest that ancestral R. speratus separated into northern and southern Japanese populations after its migration into the Japanese main islands from East China during the early Pleistocene via the East China Sea basin, which may have been exposed during that period. The Korean populations seem to have diverged recently from southern Japanese populations; this may explain the current distribution of R. speratus in the Japanese Arachipelago, and account for why it is restricted to northern areas of the Tokara Strait.

Animals↗
PubMed2006

Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells.

In cholestatic liver diseases, bile acids induce hepatocyte apoptosis and thus cause liver injury, but hepatic stellate cells (HSCs) survive in the presence of bile acids. We attempted to analyze anti-apoptotic signaling pathways in HSCs against bile acid-induced apoptosis. In immortalized human HSCs and primarily cultured rat HSCs, bile acid treatment increased the expression levels of cyclooxygenase-2 (COX-2) and Mcl-1. COX-2 induction was found to be due to transcriptional enhancement dependent on p42/44, p38 MAPK, and JNK activation, whereas Mcl-1 induction resulted from bile acid-mediated protein stabilization in a Raf-1-dependent manner. Moreover, the inhibitions of either COX-2 activity by celecoxib or Mcl-1 induction by siRNA transfection rendered HSCs susceptible to bile acid-induced apoptosis. These results imply that the bile acid-mediated inductions of COX-2 and Mcl-1 may lead to HSC survival in cholestatic liver diseases.

Animals↗
PubMed2006

Eupatilin attenuates bile acid-induced hepatocyte apoptosis.

BACKGROUND: In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against experimentally induced gastrointestinal, pancreatic, and hepatic damage. This study was undertaken to examine if eupatilin modulates bile acid-induced hepatocyte apoptosis. METHODS: Huh-BAT cells, a human hepatocellular carcinoma cell line stably transfected with a bile acid transporter, were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. Eupatilin's in vivo effect on bile acid-induced hepatocyte apoptosis was explored in bile duct-ligated rats. RESULTS: Eupatilin significantly reduced bile acid-mediated hepatocyte apoptosis by attenuating bile acid-induced caspase 8 cleavage. Eupatilin diminished the bile acid-induced activation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In particular, the eupatilin-mediated inhibition of bile acid-induced c-Jun N-terminal kinase activation was found to be responsible for attenuating caspase 8 cleavage. Moreover, eupatilin diminished hepatocyte apoptosis in bile duct-ligated rats. CONCLUSIONS: Eupatilin attenuates bile acid-induced hepatocyte apoptosis by suppressing bile acid-induced kinase activation. Therefore, eupatilin might be therapeutically efficacious in a variety of human liver diseases associated with cholestasis.

Animals↗
PubMed2006

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

OBJECTIVE: Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. DESIGN: The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. METHODS: Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. RESULTS: The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). CONCLUSION: These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Amino Acid Substitution↗
PubMed2006

First molecular data on the phylum Loricifera: an investigation into the phylogeny of ecdysozoa with emphasis on the positions of Loricifera and Priapulida.

Recent progress in molecular techniques has generated a wealth of information for phylogenetic analysis. Among metazoans all but a single phylum have been incorporated into some sort of molecular analysis. However, the minute and rare species of the phylum Loricifera have remained elusive to molecular systematists. Here we report the first molecular sequence data (nearly complete 18S rRNA) for a member of the phylum Loricifera, Pliciloricus sp. from Korea. The new sequence data were analyzed together with 52 other ecdysozoan sequences, with all other phyla represented by three or more sequences. The data set was analyzed using parsimony as an optimality criterion under direct optimization as well as using a Bayesian approach. The parsimony analysis was also accompanied by a sensitivity analysis. The results of both analyses are largely congruent, finding monophyly of each ecdysozoan phylum, except for Priapulida, in which the coelomate Meiopriapulus is separate from a clade of pseudocoelomate priapulids. The data also suggest a relationship of the pseudocoelomate priapulids to kinorhynchs, and a relationship of nematodes to tardigrades. The Bayesian analysis placed the arthropods as the sister group to a clade that includes tardigrades and nematodes. However, these results were shown to be parameter dependent in the sensitivity analysis. The position of Loricifera was extremely unstable to parameter variation, and support for a relationship of loriciferans to any particular ecdysozoan phylum was not found in the data.

Animals↗