Biomedical subjects

Kyung Hwan Kim

Publications and source records attributed to Kyung Hwan Kim.

At least 19 recordsLinked to original sources

PubMed2006

Suppression of IL-1beta expression by the Jak 2 inhibitor AG490 in cerulein-stimulated pancreatic acinar cells.

Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and an infiltration of inflammatory cells into the pancreas. Cytokines are up-regulated in pancreatic acinar cells stimulated with cerulein. In various cells and tissues, Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathway mediates inflammatory process. In the present study, we investigated whether the activation of Jak/Stat signaling mediates IL-1beta expression in pancreatic acinar AR42J cells stimulated with cerulein in vitro as well as the rats with cerulein pancreatitis in vivo using AG490, the Jak2 inhibitor. Activation of Jak2 and Stat3 were monitored by Western blot analysis for phosphorylated Jak2 and phosphorylated Stat3. mRNA expression and protein level of IL-1beta were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay (ELISA). Histological examination of pancreatic tissues were performed and serum IL-1beta levels of the rats were determined by ELISA. As a result, cerulein induced the activation of Jak2 and Stat3 as well as IL-1beta expression, which was inhibited by the treatment of AG490 in AR42J cells. In cerulein pancreatitis of the rats, edematous and inflammatory changes of the pancreas and increased serum levels of IL-1beta were suppressed by AG490 treatment. In conclusion, Jak2/Stat3 pathway may be the underlying mechanism in the pathogenesis of pancreatitis by inducing cytokines such as IL-1beta.

Animals↗

PubMed2006

Analysis of induced gamma-band activity in EEG during visual perception of Korean, English, Chinese words.

The oscillation of brain activities in the gamma-band is known to be a manifestation of the formation of neuronal assemblies that jointly constitute neural correlates of feature binding and conscious awareness. Visual word perception is a task that demands a considerable amount of cognitive resources and integration of information from multiple functionally connected neuronal circuits at various scales. Thus, it is anticipated that a substantial increase in gamma-band activity (GBA) would be observed during visual word perception. The purpose of this study was to examine whether meaningful increases in GBA occur during visual word perception and to explore similarities and differences in the amount and spatiotemporal GBA patterns while native Korean subjects perceive Korean, English, and Chinese words. We also aimed at identifying relationships between GBA increase and a behavioral measure such as response time. The results of power spectrum and time-frequency analyses showed that the increases in GBA were most significant in the prefrontal, frontal, and temporal sites, which are known to be relevant to visual word perception. The GBAs in the prefrontal and temporal sites were significantly correlated with response time. The differences in spatiotemporal patterns of GBA among languages were not prominent compared to inter-individual differences.

Adult↗

PubMed2006

Determinants of the severity of functional tricuspid regurgitation.

We performed a prospective study of patients with chronic right ventricular (RV) dilation to determine the factors associated with the degree of functional tricuspid regurgitation (FTR). We prospectively enrolled 64 patients with chronic RV dilation and measured right atrial (RA) area, RV area and its fractional area change (RVFAC), tricuspid annular diameter and contraction, tricuspid valve (TV) tethering area, and systolic pulmonary artery pressure. We also measured the RV eccentricity index and the RV sphericity index for simple presentation of RV geometry. Regurgitant orifice area of FTR was obtained for the quantification of FTR. End-systolic RV eccentricity index (r=0.73), end-diastolic RV eccentricity index (r=0.56), RA area (r=0.49), TV tethering area (r=0.37), age (r=0.31), end-systolic (r=0.42) and end-diastolic (r=0.30) tricuspid annular diameters, and left ventricular ejection fraction (r=-0.37) were significantly related to the regurgitant orifice area of FTR in univariate analysis. However, RV area, RVFAC, and systolic pulmonary artery pressure were not. In multivariate analysis, the end-systolic RV eccentricity index (p<0.001), TV tethering area (p=0.003), and end-diastolic tricuspid annulus diameter (p=0.007) showed the independent associations with regurgitant orifice area of FTR. The sensitivities and specificities for predicting more than mild FTR were found to be 79% and 82% with an end-systolic RV eccentricity index>2.0, 69% and 73% with an end-systolic tethering area>1.0 cm2, and 64% and 59% for an end-systolic tricuspid annulus diameter>3.9 cm, respectively. FTR severity was found to show the best correlation with the end-systolic RV eccentricity index. In conclusion, these findings underscore the importance of eccentric RV dilation for determining FTR severity and should lead to the development of more rational surgical approaches to FTR beyond TV annuloplasty.

Echocardiography, Doppler↗

PubMed2006

[Ca(2+)]-dependent generation of intracellular reactive oxygen species mediates maitotoxin-induced cellular responses in human umbilical vein endothelial cells.

Maitotoxin (MTX) is known as one of the most potent marine toxins involved in Ciguatera poisoning, but intracellular signaling pathways caused by MTX was not fully understood. Thus, we have investigated whether intracellular reactive oxygen species (ROS) are involved in MTX-induced cellular responses in human umbilical vein endothelial cells. MTX induced a dose-dependent increase of intracellular [Ca(2+)]. MTX stimulated the production of intracellular ROS in a dose- and time-dependent manner, which was suppressed by BAPTA-AM, an intracellular Ca(2+) che-lator. Ionomycin also elevated the ROS production in a dose-dependent manner. MTX elevated transamidation activity in a time-dependent manner and the activation was largely inhibited by transfection of tissue transglutaminase siRNA. The activation of tissue transglutaminase and ERK1/2 by MTX was sup-pressed by BAPTA-AM or ROS scavengers. In addition, MTX-induced cell death was significantly de-layed by BAPTA-AM or a ROS scavenger. These results suggest that [Ca(2+)]-dependent generation of in-tracellular ROS, at least in part, play an important role in MTX-stimulated cellular responses, such as activation of tTGase, ERK phosphorylation, and in-duction of cell death, in human umbilical vein endothelial cells.

Calcium↗

PubMed2006

Improvement of spike train decoder under spike detection and classification errors using support vector machine.

The successful decoding of kinematic variables from spike trains of motor cortical neurons is essential for cortical neural prosthesis. Spike trains from each single unit must be extracted from extracellular neural signals and, thus, spike detection and sorting procedure is indispensable but the detection and sorting may involve considerable error. Thus, a decoding algorithm should be robust with respect to spike train errors. Here, we show that spike train decoding algorithms employing nonlinear mapping, especially a support vector machine (SVM), may be more advantageous contrary to previous results which showed that an optimal linear filter is sufficient. The advantage became more conspicuous in the case of erroneous spike trains. Using the SVM, satisfactory training of the decoder could be achieved much more easily, compared to the case of using a multilayer perceptron, which has been employed in previous studies. Tests were performed on simulated spike trains from primary motor cortical neurons with a realistic distribution of preferred direction. The results suggest the possibility that a neuroprosthetic device with a low-quality spike sorting preprocessor can be achieved by adopting a spike train decoder that is robust to spike sorting errors.

Action Potentials↗

PubMed2005

Comparison of spatiotemporal cortical activation pattern during visual perception of Korean, English, Chinese words: an event-related potential study.

The aim of this study was to compare spatiotemporal cortical activation patterns during the visual perception of Korean, English, and Chinese words. The comparison of these three languages offers an opportunity to study the effect of written forms on cortical processing of visually presented words, because of partial similarity/difference among words of these languages, and the familiarity of native Koreans with these three languages at the word level. Single-character words and pictograms were excluded from the stimuli in order to activate neuronal circuitries that are involved only in word perception. Since a variety of cerebral processes are sequentially evoked during visual word perception, a high-temporal resolution is required and thus we utilized event-related potential (ERP) obtained from high-density electroencephalograms. The differences and similarities observed from statistical analyses of ERP amplitudes, the correlation between ERP amplitudes and response times, and the patterns of current source density, appear to be in line with demands of visual and semantic analysis resulting from the characteristics of each language, and the expected task difficulties for native Korean subjects.

Cerebral Cortex↗

PubMed2005

Shank2 associates with and regulates Na+/H+ exchanger 3.

Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3(-) absorption across a wide range of epithelia in the digestive and renal-genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor proteins play an important role in regulating the trafficking and activity of NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays led us to the PDZ-based adaptor Shank2. The interaction between Shank2 and NHE3 was further confirmed by immunoprecipitation and surface plasmon resonance studies. When expressed in PS120/NHE3 cells, Shank2 increased the membrane expression and basal activity of NHE3 and attenuated the cAMP-dependent inhibition of NHE3 activity. Furthermore, knock-down of native Shank2 expression in Caco-2 epithelial cells by RNA interference decreased NHE3 protein expression as well as activity but amplified the inhibitory effect of cAMP on NHE3. These results indicate that Shank2 is a novel NHE3 interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity.

Animals↗

PubMed2005

An fMRI study of Chinese character reading and picture naming by native Korean speakers.

Chinese characters appear in the currently used Korean language, and the system used for writing system the Korean language consists of a mixture of the Korean alphabet and Chinese characters. In the present study, neural mechanisms involved in reading a single Chinese character words and naming pictures by Korean native speakers were investigated using a functional magnetic resonance imaging technique. The findings show a right hemispheric dominance within the occipito-temporal and the left middle/medial frontal area for both reading Chinese characters and naming pictures. This should reflect the specific visual processing of reading Chinese characters. Additional activations in inferior frontal and cingulage gyrus were also observed. The activations of inferior parietal region and thalamus are of interest, since we assume that these activations are strongly related to the phonological status of single Chinese character words rather than two character words that are typically used by Korean native speakers.

Adult↗

PubMed2005

The synaptic microcircuitry associated with primary afferent terminals in the interpolaris and caudalis of trigeminal sensory nuclear complex.

Previous ultrastructural studies indicating a higher number of axoaxonic contacts on individual low-threshold mechanoreceptive afferents in the principalis (Vp) than in the oralis (Vo) of cat trigeminal sensory nuclear complex (TSNC) suggest that the synaptic microcircuitry associated with primary afferents manifests unique differences across the sensory nuclei of TSNC. To address this issue, we analyzed synaptic microcircuits associated with fast adapting vibrissa afferent terminals in the interpolaris (Vi) and caudalis (Vc, laminae III/IV) by using intraaxonal injections of horseradish peroxidase (HRP) in cats. Forty-two and 65 HRP-labeled boutons were analyzed in the Vi and Vc, respectively. The labeled boutons contained clear, spherical vesicles. They most frequently formed asymmetric axodendritic synapses and were commonly postsynaptic to unlabeled axon terminals containing pleomorphic vesicles (p-endings) with symmetric junctions. The examination of synaptic contacts over the entire surface of individual boutons indicated that the afferent boutons made contacts with an average of two postsynaptic targets in the Vi and Vc. In contrast, axoaxonic contacts, and labeled boutons participating in synaptic triads, where p-endings contacted both the boutons and their postsynaptic targets, were, on average, higher in the Vi than in the Vc. These results suggest that the output of sensory information conveyed through low-threshold mechanoreceptive afferents is more strongly controlled at the level of the first synapse by presynaptic and postsynaptic mechanisms in the Vi responsible for sensory discriminative functions than in the Vc for sensorimotor reflexive functions.

Afferent Pathways↗

PubMed2005

Oriented immobilization of antibodies by a self-assembled monolayer of 2-(biotinamido)ethanethiol for immunoarray preparation.

Orientation of antibodies is very important in the preparation of immunoarrays to keep the activity of antibodies on solid surfaces. Thus, we synthesized a new bifunctional compound, 2-(biotinamido)ethanethiol, and investigated whether the thiol compound is useful to analyze antibody-antigen interactions on immunoarrays with a spectral SPR biosensor. The synthesized organic thiol was characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. 2-(Biotinamido)ethanethiol formed a monolayer on a gold surface and properly immobilized antibodies via streptavidin and biotinylated protein G. Optimal molar ratio of 2-(biotinamido)ethanethiol and mercaptohexanol for antigen-antibody interactions was 1:2. Thus, 2-(biotinamido)ethanethiol is an useful bifunctional linker in the preparation of immunoarrays on gold surfaces.

Antibodies, Immobilized↗

PubMed2005

NADPH oxidase and apoptosis in cerulein-stimulated pancreatic acinar AR42J cells.

Apoptosis linked to oxidative stress has been implicated in pancreatitis. We investigated whether NADPH oxidase mediates apoptosis in cerulein-stimulated pancreatic acinar AR42J cells. We report here that cerulein treatment resulted in the activation of NADPH oxidase, as determined by ROS production, translocation of cytosolic subunits p 47(phox) and p 67(phox) to the membrane, and interaction between NADPH oxidase subunits. Cerulein induced Ca(2+) oscillation, the expression of apoptotic genes p53 and bax, and apoptotic indices (DNA fragmentation, TUNEL staining, caspase 3 activity, decrease in cell viability) in AR42J cells. Treatment with a Ca(2+) chelator, BAPTA-AM, or transfection with antisense oligonucleotides for NADPH oxidase subunits p22(phox) and p 47(phox) inhibited cerulein-induced ROS production, translocation of NADPH oxidase cytosolic subunits p 47(phox) and p 67(phox) to the membrane, and the expression of apoptotic genes and apoptotic indices, as compared to the cells without treatment and those transfected with the corresponding sense oligonucleotides. These results indicate that NADPH oxidase may mediate ROS-induced apoptosis in pancreatic acinar cells in a Ca(2+)-dependent manner.

Animals↗

PubMed2005

Superiority of nonlinear mapping in decoding multiple single-unit neuronal spike trains: a simulation study.

One of the most important building blocks of the brain-machine interface (BMI) based on neuronal spike trains is the decoding algorithm, a computational method for the reconstruction of desired information from spike trains. Previous studies have reported that a simple linear filter is effective for this purpose and that no noteworthy gain is achieved from the use of nonlinear algorithms. In order to test this premise, we designed several decoding algorithms based on the linear filter, and two nonlinear mapping algorithms using multilayer perceptron (MLP) and support vector machine regression (SVR). Their performances were assessed using multiple neuronal spike trains generated by a biophysical neuron model and by a directional tuning model of the primary motor cortex. The performances of the nonlinear algorithms, in general, were superior. The advantages of using nonlinear algorithms were more profound for cases where false-positive/negative errors occurred in spike trains. When the MLPs were trained using trial-and-error, they often showed disappointing performance comparable to that of the linear filter. The nonlinear SVR showed the highest performance, and this may be due to the superiority of SVR in training and generalization.

Action Potentials↗

PubMed2005

Long-term result of 1144 CarboMedics mechanical valve implantations.

BACKGROUND: It has been reported that the CarboMedics mechanical valve has acceptable valve-related complication rates. The aim of this study was to evaluate the long-term performance of the CarboMedics valve. METHODS: Between August 1988 and September 1999, we implanted 1144 CarboMedics valves in 850 patients (aortic, 179; mitral, 385; double-valve, 234; tricuspid, 52). Mean patient age was 44.5 +/- 12.5 years. Follow-up was completed in 95.3% and the median follow-up period was 7.9 years (6753 patient-years). Patients were divided into four groups according to implanted valve location and number (aortic, mitral, double, and tricuspid valve groups). RESULTS: The overall hospital mortality rate was 3.4%, and the mortality rates in these groups were 1.7% in the aortic, 2.6% in the mitral, 4.7% in the double, and 9.6% in the tricuspid valve. The tricuspid valve group revealed a significantly higher mortality rate than the aortic and mitral valve groups (p < 0.05). Overall 10-year survival was 87.1% +/- 2.6%, 88.9% +/- 1.7%, 82.4% +/- 2.9%, and 77.5% +/- 7.0% in the aortic, mitral, double, and tricuspid valve groups, respectively. Age and tricuspid valve replacement were identified as significant risk factors of long-term survival by multivariate analysis (p < 0.05), and 99.4% +/- 0.6%, 98.2% +/- 0.8%, 99.2% +/- 0.8%, and 87.6% +/- 0.5% in the aortic, mitral, double, and tricuspid valve groups were free of valve thrombosis at 10 years. The tricuspid valve group demonstrated a significantly higher rate of valve thrombosis (p < 0.05). CONCLUSIONS: This long-term study of patients that received CarboMedics valve implantation demonstrates that the CarboMedics prosthetic valve has an acceptable incidence of valve-related complications. However, it should be noted that tricuspid valve replacement indicated a higher level of overall mortality and valve thrombosis.

Adult↗

PubMed2005

NADPH oxidase mediates interleukin-6 expression in cerulein-stimulated pancreatic acinar cells.

NADPH oxidase produces a large amount of reactive oxygen species (ROS) mainly in phagocytic cells. ROS are involved in NF-kappaB activation, cytokine expression and thus, pathogenesis of pancreatitis. However, the source of ROS in pancreatic acinar cells has not been clarified. Cerulein rapidly induces acute and edematous form of pancreatitis. We investigated whether pancreatic acinar cells contain NADPH oxidase, and whether NADPH oxidase mediates interleukin-6 (IL-6) in pancreatic acinar AR42J cells stimulated with cerulein. Expression of NADPH oxidase subunits and NADPH oxidase activity were determined in the cells by immunofluorescence staining and lucigenin luminescence, respectively. Oxidant-sensitive nuclear transcription factor NF-kappaB activation was monitored by electrophoretic mobility shift assay. IL-6 expression was determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbant assay. NADPH oxidase inhibitor diphenylene iodonium (DPI), antioxidant rebamipide, and antisense oligonucleotides (AS ODNs) for NADPH oxidase subunits p22phox and p47phox were used to determine the involvement of NADPH oxidase in NF-kappaB activation and IL-6 expression in AR42J cells. As a result, pancreatic acinar AR42J cells constitutively express NADPH oxidase subunits p67phox and p47phox in the cytosol and Nox1 and p22phox in the membrane. Cerulein-stimulated NADPH oxidase activity and induced NF-kappaB activation and IL-6 expression in AR42J cells. Treatment of DPI or rebamipide and transfection of AS ODNs for NADPH oxidase subunits suppressed cerulein-induced NF-kappaB activation and IL-6 expression compared to S ODNs. In conclusion, NADPH oxidase may mediate the expression of inflammatory cytokines by stimulating NF-kappaB activation in pancreatic acinar cells during the course of pancreatitis.

Animals↗

PubMed2005

Base treatment corrects defects due to misfolding of mutant cystic fibrosis transmembrane conductance regulator.

BACKGROUND & AIMS: The most common form of the disease-causing cystic fibrosis transmembrane conductance regulator mutation, DeltaF508, leads to a misfolded protein that undergoes endoplasmic reticulum-associated degradation. Retrieval of misfolded protein from the cis-Golgi or pre-Golgi intermediate compartment is a critical factor in endoplasmic reticulum retention and degradation of DeltaF508 protein. Therefore, the inhibition of retrograde Golgi-to-endoplasmic reticulum traffic by the alkalinization of Golgi lumen may permit functional DeltaF508 protein to reach the cell surface. METHODS: Functional and biochemical effects of alkaline treatment on misfolded cystic fibrosis transmembrane conductance regulator-induced defects were measured in CFPAC-1 cells, which endogenously express DeltaF508 cystic fibrosis transmembrane conductance regulator, and in CHO cells, which heterologously express DeltaF508 cystic fibrosis transmembrane conductance regulator. The animal survival rate and the functional expression of cystic fibrosis transmembrane conductance regulator proteins were analyzed in homozygous DeltaF508 mice after chronic treatment with weak base NaHCO3. RESULTS: In CFPAC-1 and CHO cells, intracellular alkalization by reducing carbon dioxide concentrations in a carbon dioxide incubation chamber or intra-Golgi alkalization by bafilomycin A1 treatment increased the membrane expression of DeltaF508 protein and cystic fibrosis transmembrane conductance regulator-dependent anion transport. Notably, chronic administration of NaHCO3 increased the long-term survival of homozygous DeltaF508 mice and induced the functional expression of cystic fibrosis transmembrane conductance regulator in the luminal membrane of intestinal epithelium. CONCLUSIONS: We found that base treatments correct misfolded cystic fibrosis transmembrane conductance regulator-induced defects in vitro and in vivo. These results imply that the alkalization of intracellular compartments, in particular, Golgi or pre-Golgi intermediate compartments, can be a potential therapeutic target for the loss-of-function type of conformational diseases.

1-Methyl-3-isobutylxanthine↗

PubMed2004

Pharmacological characterization of rebamipide: its cholecystokinin CCK1 receptor binding profile and effects on Ca2+ mobilization and amylase release in rat pancreatic acinar cells.

We previously reported that rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]-propionic acid) generated oscillations of intracellular Ca2+ concentration ([Ca2+]i) probably through the activation of cholecystokinin type 1 (CCK1) receptors in rat pancreatic acinar cells. Therefore, in the present study, we aimed to establish the pharmacological characteristics of rebamipide in rat pancreatic acinar cells. CCK-8S and rebamipide inhibited [125I]BH-CCK-8S binding to rat pancreatic acinar cell membranes with IC50 values of 3.13 nM and 37.7 microM, respectively. CCK-8S usually evoked [Ca2+]i oscillations at concentrations lower than 50 pM, and it induced biphasic [Ca2+]i increases at higher concentrations. In contrast to CCK-8S, rebamipide only induced [Ca2+]i oscillations at all the concentrations we used in this study. In addition, rebamipide was shown to inhibit high concentrations of CCK-8S-induced biphasic increases in [Ca2+]i, suggesting that rebamipide might be a partial agonist at cholecystokinin CCK1 receptors. Although rebamipide induced [Ca2+]i oscillations by activating the cholecystokinin CCK1 receptors, rebamipide did not cause amylase release and only inhibited CCK-stimulated amylase release reversibly and dose-dependently. However, rebamipide did not inhibit carbachol-, vasoactive intestinal polypeptide (VIP)-, and forskolin-induced amylase releases. These data indicate that rebamipide functions as a partial agonist for Ca2+ -mobilizing action, and it is also an antagonist for the amylase-releasing action of CCK.

Alanine↗

PubMed2004

Improved ballistocardiac artifact removal from the electroencephalogram recorded in fMRI.

The simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance image (fMRI) is a promising tool that is capable of providing high spatiotemporal brain mapping, with each modality supplying complementary information. One of the major barriers to obtain high-quality simultaneous EEG/fMRI data is that pulsatile activity due to the heartbeat induces significant artifacts in the EEG. The purpose of this study was to develop a novel algorithm for removing heartbeat artifact, thus overcoming problems associated with previous methods. Our method consists of a mean artifact wave form subtraction, the selective removal of wavelet coefficients, and a recursive least-square adaptive filtering. The recursive least-square adaptive filtering operates without dedicated sensor for the reference signal, and only when the mean subtraction and wavelet-based noise removal is not satisfactory. The performance of our system has been assessed using simulated data based on experimental data of various spectral characteristics, and actual experimental data of alpha-wave-dominant normal EEG and epileptic EEG.

Adult↗

PubMed2004

Spatiotemporal brain activation pattern during word/picture perception by native Koreans.

The purpose of this study is to explore spatiotemporal brain activation patterns during perception of words from three different languages (Korean, English, Chinese) and pictures. Using 64 channel event-related potential (ERP) recording and source localization using distributed source model, we investigated, with high temporal resolution, whether similar or different spatiotemporal patterns of brain activation are involved in the perception of words of different languages and/or pictures. Experimental results seem to corroborate left hemispheric dominance in language processing, and temporal/spatial characteristics in word perception revealed by previous ERP and neuroimaging studies. Observed differences in spatial pattern of activation at specific time periods between English and Korean, and Korean and Chinese, could be explained in terms of required visual pattern analysis due to the orthographic characteristics of each language.

Adult↗