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Biomedical subjects

Won Tae Kim

Publications and source records attributed to Won Tae Kim.

6 recordsLinked to original sources
PubMed2026

Transcriptome-based high-frequency recurrence index predicts frequent recurrence in non-muscle-invasive bladder cancer after Bacillus Calmette-Guérin therapy.

BACKGROUND: High-frequency recurrence (HfR,&#x2009;&#x2265;&#x2009;2 recurrences) in non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical burden. Current risk models, such as the European Organization for Research and Treatment of Cancer (EORTC), the European Association of Urology (EAU), and the UROMOL classification, offer limited predictive accuracy for identifying patients at risk for frequent recurrence despite appropriate treatment. METHODS: A 75-gene high-frequency recurrence index (HfRI) was constructed by selecting recurrence-associated genes using differential expression and Cox regression analyses. The HfRI was computed as a weighted sum of normalized gene expression values. The model was trained on a discovery cohort and validated in multiple cohorts (n&#x2009;=&#x2009;1379) using machine-learning approaches. Clinical relevance was assessed using recurrence-free survival (RFS) and Cox models, and predictive performance was compared with that of the EORTC, EAU, and UROMOL classifications using the area under the curve (AUC) and the concordance index (c-index). RESULTS: The HfRI robustly stratified patients into high-risk and low-risk groups across six independent NMIBC cohorts. Patients classified as HfRI-high had a significantly greater likelihood of experiencing&#x2009;&#x2265;&#x2009;2 recurrences (&#x3c7;2, p&#x2009;=&#x2009;0.001) and showed markedly reduced RFS (log-rank test, p&#x2009;<&#x2009;0.001). The adverse prognostic effect of the HfRI persisted even among patients treated with BCG therapy (log-rank test, p&#x2009;=&#x2009;0.02). Multivariate analysis revealed that the HfRI was an independent predictor of HfR (HR&#x2009;=&#x2009;2.82, 95% CI&#x2009;=&#x2009;1.89-4.20, p&#x2009;<&#x2009;0.001). Compared with established clinical risk classifiers, the HfRI demonstrated superior predictive performance (AUC&#x2009;=&#x2009;0.736, c-index&#x2009;=&#x2009;0.673) in terms of the EORTC (AUC&#x2009;=&#x2009;0.594), EAU (AUC&#x2009;=&#x2009;0.557) risk groups, and UROMOL2021 (AUC&#x2009;=&#x2009;0.596) classification. Pathway analysis revealed that HfRI-high tumors were characterized by upregulation of cell cycle progression and DNA replication pathways, accompanied by suppression of immune signaling pathways. These biological features provide a mechanistic explanation for the reduced responsiveness to intravesical BCG therapy, underscoring the role of HfRI not only as a predictor of recurrence risk but also as a biomarker capable of identifying patients unlikely to benefit from standard BCG treatment. CONCLUSIONS: HfRI represents a robust, transcriptome-based tool for predicting frequent recurrence in NMIBC patients. The HfRI supports earlier identification of patients at risk of high-frequency recurrence, thereby supporting personalized treatment strategies.

Humans↗
PubMed2006

Mutations of acetylcholinesterase1 contribute to prothiofos-resistance in Plutella xylostella (L.).

Insensitive acetylcholinesterase (AChE) is involved in the resistance of organophosphorous and carbamate insecticides. We cloned a novel full-length AChE cDNA encoding ace1 gene from adult heads of the diamondback moth (DBM, Plutella xylostella). The ace1 gene encoding 679 amino acids has conserved motifs including catalytic triad, choline-binding site and acyl pocket. Northern blot analysis revealed that the ace1 gene was expressed much higher than the ace2 in all examined body parts. The biochemical properties of expressed AChEs showed substrate specificity for acetylthiocholine iodide and inhibitor specificity for BW284C51 and eserine. Three mutations of AChE1 (D229G, A298S, and G324A) were identified in the prothiofos-resistant strain, two of which (A298S and G324A) were expected to be involved in the prothiofos-resistance through three-dimensional modeling. In vitro functional expression of AChEs in Sf9 cells revealed that only resistant AChE1 is less inhibited with paraoxon, suggesting that resistant AChE1 is responsible for prothiofos-resistance.

Acetylcholinesterase↗
PubMed2006

Phase separating bulk metallic glass: a hierarchical composite.

Phase separating systems present a unique opportunity for designing composites with hierarchical microstructure at different length scales. We report here our success in synthesizing phase separating metallic glasses exhibiting the entire spectrum of microstructural possibilities expected from a phase separating system. In particular, we report novel core shell and hierarchical structures of spherical glassy droplets, resulting from critical wetting behavior and limited diffusion. We also report synthesis of a bulk phase separating glass in a metallic glass system. The combination of unique core shell and hierarchical structures in metallic glass systems opens a new avenue for the microstructure design of metallic glasses.

Journal Article↗
PubMed2006

Simulation of Ca2+-activated Cl- current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca2+ dynamics.

In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na+-Ca2+ exchange (NCX). We found that these currents were mediated by a Ca2+-activated Cl- current. Based on the recent reports describing the atrial Ca2+ transients, the Ca2+ transient at the subsarcolemmal space was initiated and then diffused into the cytosolic space. Because the myocardium in the pulmonary vein is an extension of the atrium, the Ca2+-activated Cl- current may reflect the subsarcolemmal Ca2+ dynamics. We tried to predict the subsarcolemmal Ca2+ dynamics by simulating these current traces. According to recent reports on the geometry of atrial myocytes, we assumed that there were three compartments of sarcoplasmic reticulum (SR): a network SR, a junctional SR and a central SR. Based on these structures, we also divided the cytosolic space into three compartments: the junctional, subsarcolemmal and cytosolic spaces. Geometry information and cellular capacitance suggested that there were essentially no T-tubules in these cells. The basic physical data, such as the compartmental volumes, the diffusion coefficients and the stability coefficients of the Ca2+ buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca2+ channel, the rapid activating outward rectifier K+ channel, the Na+-K+ pump, the SR Ca2+-pump, the ryanodine receptor, the Ca2+-activated Cl- channel and the dynamics of Na+, K+, Ca2+ and Cl-. In these conditions, we could successfully reconstruct the Ca2+-activated Cl- currents. The simulation allowed estimation of the Ca2+ dynamics of each compartment and the distribution of the Ca2+-activated Cl- channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.

Action Potentials↗
PubMed2006

Phacoemulsification and acryl foldable intraocular lens implantation in dogs: 32 cases.

This study evaluated the surgical outcome and complications of phacoemulsification and the implantation of an acryl foldable intraocular lens (IOL) with a squared edge in dogs with cataracts. Thirty-two eyes from 26 dogs were examined. The mean follow up period was 75.9 days ranging from 23 to 226 days. The complications after phacoemulsification were posterior capsular opacity (PCO) around the IOL (n = 11), ocular hypertension (n = 4), focal posterior synechia (n = 4), hyphema (n = 3) and corneal ulcer (n = 2). The complications associated with the IOL were decenteration of the optic (n = 2) and ventral haptic displacement (n = 1). Most cases of PCO were found only around the margin of the IOL, and all eyes had vision during the observation period. In conclusion, the implantation of an acryl-foldable lens with a squared edge at the time of phacoemulsification is an effective method for preserving the central visual field of dogs with cataract.

Animals↗
PubMed2005

Molecular characterization of two acetylcholinesterase genes from the oriental tobacco budworm, Helicoverpa assulta (Guenée).

Acetylcholinesterase (AChE) has been known to be the target of organophosphorous and carbamate insecticides. Only a single AChE, however, existed in insects and was involved in insecticide resistance, recently another AChE is reported in mosquitoes and aphids. We have cloned cDNAs encoding two ace genes, designated as Ha-ace1 and Ha-ace2 by a combined degenerate PCR and RACE strategy from adult heads of the oriental tobacco budworm, Helicoverpa assulta. The Ha-ace1 and Ha-ace2 genes encode 664 and 647 amino acids, respectively and have conserved motifs including a catalytic triad, a choline-binding site and an acyl pocket. Both Ha-AChEs were determined to be secretory proteins based on the existence of a signal peptide. The Ha-ace1 gene, the first reported ace1 in lepidopterans, belongs to the ace1 subfamily whereas the Ha-ace2 gene showed high similarity to those in the ace2 subfamily. Phylogenetic analysis showed that the Ha-ace1 gene was completely diverged from the Ha-ace2, suggesting that the Ha-ace genes are duplicated. Quantitative real time-PCR revealed that expression level of the Ha-ace1 gene was much higher than that of the Ha-ace2 in all body parts examined. The biochemical properties of purified proteins by affinity chromatography showed substrate specificity for acetylthiocholine iodide, and inhibitor specificity for BW284C51 and eserine and their peptide sequences partially identified by a MALDI-TOF mass spectrometer demonstrated that two Ha-AChEs were expressed in vivo.

Acetylcholinesterase↗