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S H Chung

Publications and source records attributed to S H Chung.

At least 37 records · Page 2Linked to original sources
PubMed2000

Molecular dynamics estimates of ion diffusion in model hydrophobic and KcsA potassium channels.

Molecular dynamics simulations are carried out to obtain estimates of diffusion coefficients of biologically important Na+, K+, Ca2+ and Cl- ions in hydrophobic cylindrical channels with varying radii and large reservoirs. Calculations for the cylindrical channels are compared to those for the KcsA potassium channel, for which the protein structure has recently been determined from X-ray diffraction experiments. Our results show that ion diffusion is maintained at reasonably high levels even within narrow channels, and does not support the very small diffusion coefficients used in some continuum models in order to fit experimental data. The present estimates of ion diffusion coefficients are useful in the calculation of channel conductance using the Poisson-Nernst-Planck theory, or Brownian dynamics.

Algorithms↗
PubMed2000

Pharmacological characterization of (10bS)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) as a new alpha2-adrenoceptor antagonist.

Alpha2-adrenoceptor antagonists, which can enhance synaptic norepinephrine levels by blocking feedback inhibition processes, are potentially useful in the treatment of disease states such as depression, memory impairment, impotence and sexual dysfunction. (10bS)-1,2,3,5,6,10b-Hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) was evaluated in several in vitro biological tests to establish its pharmacological profile of activities as an alpha2-adrenoceptor antagonist. Saturation binding assay revealed that [3H]rauwolscine bound to the alpha2-adrenoceptors with a Kd value of 6.3+/-0.5 nM and a Bmax value of 251+/-39 fmol/mg protein in rat cortical synaptic membranes. Competitive binding assay showed that YSL-3S inhibited the binding of [3H]rauwolscine (1 nM) in a concentration-dependent manner with a Ki value of 98.2+/-12.1 nM while it did not inhibit the binding of [3H]cytisine (1.25 nM) to neuronal nicotinic cholinergic receptors. The Ki values of yohimbine, clonidine and norepinephrine for [3H]rauwolscine binding were 15.8+/-1.0, 40.1+/-5.9 and 40.0+/-11.5 nM, respectively. In addition, the binding affinity of YSL-3S for alpha2-adrenoceptors was higher than that of its antipode and the racemic mixture. The functional activity of YSL-3S at the presynaptic alpha2-adrenoceptors was assessed using the prostatic portion of the rat vas deferens. Clonidine inhibited field-stimulated contractions of the vas deference in a dose-dependent manner. The presence of YSL-3S or yohimbine caused a parallel, rightward the dose-response curve of clonidine in a dose-dependent manner, indicating an antagonistic action at the presynaptic alpha2-adrenoceptors. The pA2 values of yohimbine and YSL-3S were 7.66+/-0.13 and 6.64+/-0.18, respectively. The results indicate that YSL-3S acts as a competitive antagonist at presynaptic alpha2-adrenoceptors with a potency approximately ten times lower than yohimbine, but is devoid of binding affinity for neuronal nicotinic cholinergic receptors.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2000

Lipid peroxidation inhibitory activity of some constituents isolated from the stem bark of Eucalyptus globulus.

Twelve compounds with lipid peroxidation inhibitory activity were isolated from the stem bark of E. globulus. Their structures were assigned as a new aromatic monoterpene (1) and eleven known compounds, pinoresinol (2), vomifoliol (3), 3,4,5-trimethoxyphenol 1-O-beta-D-(6'-O-galloyl)glucopyranoside (4), methyl gallate (5), rhamnazin (6), rhamnetin (7), eriodictyol (8), quercetin (9), taxifolin (10), engelitin (11), and catechin (12) on the basis of UV, mass, and NMR spectroscopic analyses. These compounds except vomifoliol significantly inhibited lipid peroxidation in rat liver microsome.

Animals↗
PubMed2000

Tests of continuum theories as models of ion channels. I. Poisson-Boltzmann theory versus Brownian dynamics.

Continuum theories of electrolytes are widely used to describe physical processes in various biological systems. Although these are well-established theories in macroscopic situations, it is not clear from the outset that they should work in small systems whose dimensions are comparable to or smaller than the Debye length. Here, we test the validity of the mean-field approximation in Poisson-Boltzmann theory by comparing its predictions with those of Brownian dynamics simulations. For this purpose we use spherical and cylindrical boundaries and a catenary shape similar to that of the acetylcholine receptor channel. The interior region filled with electrolyte is assumed to have a high dielectric constant, and the exterior region representing protein a low one. Comparisons of the force on a test ion obtained with the two methods show that the shielding effect due to counterions is overestimated in Poisson-Boltzmann theory when the ion is within a Debye length of the boundary. As the ion gets closer to the boundary, the discrepancy in force grows rapidly. The implication for membrane channels, whose radii are typically smaller than the Debye length, is that Poisson-Boltzmann theory cannot be used to obtain reliable estimates of the electrostatic potential energy and force on an ion in the channel environment.

Algorithms↗
PubMed2000

Tests of continuum theories as models of ion channels. II. Poisson-Nernst-Planck theory versus brownian dynamics.

We test the validity of the mean-field approximation in Poisson-Nernst-Planck theory by contrasting its predictions with those of Brownian dynamics simulations in schematic cylindrical channels and in a realistic potassium channel. Equivalence of the two theories in bulk situations is demonstrated in a control study. In simple cylindrical channels, considerable differences are found between the two theories with regard to the concentration profiles in the channel and its conductance properties. These differences are at a maximum in narrow channels with a radius smaller than the Debye length and diminish with increasing radius. Convergence occurs when the channel radius is over 2 Debye lengths. These tests unequivocally demonstrate that the mean-field approximation in the Poisson-Nernst-Planck theory breaks down in narrow ion channels that have radii smaller than the Debye length.

Algorithms↗
PubMed2000

Biocompatibility of new peritoneal dialysis solutions: what can we hope to achieve?

Despite the bioincompatibility of the "old", standard, high glucose, lactate-buffered peritoneal dialysis (PD) solutions, PD is itself a highly successful dialysis modality with patient survival equivalent to that of hemodialysis (HD) during the initial 3 - 5 years of dialysis therapy. Nevertheless, PD technique survival is often limited by infectious complications and alterations in the structure and function of the peritoneal membrane. These local changes also have a negative impact on patient survival owing to systemic effects such as those often seen in patients with high peritoneal transport rate and loss of ultrafiltration (UF) capacity. Patient mortality remains unacceptably high in both HD and PD patients, with most premature deaths being associated with signs of malnutrition, inflammation, and atherosclerotic cardiovascular disease (MIA syndrome). These systemic signs are likely to be influenced by PD solutions both directly and indirectly (via changes in the peritoneal membrane). New, biocompatible PD solutions may have favorable local effects (viability and function of the peritoneal membrane) and systemic effects (for example, on MIA syndrome). Amino acid-based solution [Nutrineal (N): Baxter Healthcare Corporation, Deerfield, IL, U.S.A.] may improve nutritional status as well as peritoneal membrane viability. Bicarbonate/lactate-buffered solution [Physioneal (P): Baxter Healthcare Corporation] may ameliorate local and systemic effects of low pH, high lactate, and high glucose degradation products. Icodextrin-based solution [Extraneal (E): Baxter Healthcare SA, Castlebar, Ireland] may improve hypertension and cardiovascular problems associated with fluid overload and may extend time on therapy in patients with loss of UF capacity. The positive effects of each of these new, biocompatible solutions have been demonstrated in several studies. It is likely that the combined use of N, P, and E solutions will produce favorable synergies in regard to both local effects (peritoneal viability) and systemic effects (less malnutrition, inflammation, and fluid overload). Solution combination is an exciting area for clinical study in the coming years. Furthermore, dialysis fluid additives such as hyaluronan, which protects and improves the function of the peritoneal membrane, may further improve PD solutions. The new, biocompatible PD solutions represent an entirely new era in the evolution of the PD therapy; they are likely to have markedly positive effects on both PD technique and PD patient survival in coming years.

Amino Acids↗
PubMed1999

Comparison of the effects on secretion in chromaffin and PC12 cells of Rab3 family members and mutants. Evidence that inhibitory effects are independent of direct interaction with Rabphilin3.

The Rab class of low molecular weight GTPases has been implicated in the regulation of vesicular trafficking between membrane compartments in eukaryotic cells. The Rab3 family consisting of four highly homologous isoforms is associated with secretory granules and synaptic vesicles. Many different types of experiments indicate that Rab3a is a negative regulator of exocytosis and that its GTP-bound form interacts with Rabphilin3, a possible effector. Overexpression of Rabphilin3 in chromaffin cells enhances secretion. We have investigated the expression, localization, and effects on secretion of the various members of the Rab3 family in bovine chromaffin and PC12 cells. We found that Rab3a, Rab3b, Rab3c, and Rab3d are expressed to varying degrees in PC12 cells and in a fraction enriched in chromaffin granule membranes from the adrenal medulla. Immunocytochemistry revealed that all members of the family when overexpressed in PC12 cells localize to secretory granules. Binding constants for the interaction of the GTP-bound forms of Rab3a, Rab3b, Rab3c, and Rab3d with Rabphilin3 were comparable (Kd = 10-20 nM). Overexpression of each of the four members of the Rab3 family inhibited secretion. Mutations in Rab3a were identified that strongly impaired the ability of the GTP-bound form to interact with Rabphilin3. The mutated proteins inhibited secretion similarly to wild type Rab3a. Although Rab3a and Rabphilin3 are located on the same secretory granule or secretory vesicle and interact both in vitro and in situ, it is concluded that the inhibition of secretion by overexpression of Rab3a is unrelated to its ability to interact with Rabphilin3.

Adaptor Proteins, Signal Transducing↗
PubMed1999

The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma.

To test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity.

Animals↗
PubMed1999

Molecular dynamics study of the KcsA potassium channel.

The structural, dynamical, and thermodynamic properties of a model potassium channel are studied using molecular dynamics simulations. We use the recently unveiled protein structure for the KcsA potassium channel from Streptomyces lividans. Total and free energy profiles of potassium and sodium ions reveal a considerable preference for the larger potassium ions. The selectivity of the channel arises from its ability to completely solvate the potassium ions, but not the smaller sodium ions. Self-diffusion of water within the narrow selectivity filter is found to be reduced by an order of magnitude from bulk levels, whereas the wider hydrophobic section of the pore maintains near-bulk self-diffusion. Simulations examining multiple ion configurations suggest a two-ion channel. Ion diffusion is found to be reduced to approximately 1/3 of bulk diffusion within the selectivity filter. The reduced ion mobility does not hinder the passage of ions, as permeation appears to be driven by Coulomb repulsion within this multiple ion channel.

Bacterial Proteins↗
PubMed1999

Permeation of ions across the potassium channel: Brownian dynamics studies.

The physical mechanisms underlying the transport of ions across a model potassium channel are described. The shape of the model channel corresponds closely to that deduced from crystallography. From electrostatic calculations, we show that an ion permeating the channel, in the absence of any residual charges, encounters an insurmountable energy barrier arising from induced surface charges. Carbonyl groups along the selectivity filter, helix dipoles near the oval chamber, and mouth dipoles near the channel entrances together transform the energy barrier into a deep energy well. Two ions are attracted to this well, and their presence in the channel permits ions to diffuse across it under the influence of an electric field. Using Brownian dynamics simulations, we determine the magnitude of currents flowing across the channel under various conditions. The conductance increases with increasing dipole strength and reaches its maximum rapidly; a further increase in dipole strength causes a steady decrease in the channel conductance. The current also decreases systematically when the effective dielectric constant of the channel is lowered. The conductance with the optimal choice of dipoles reproduces the experimental value when the dielectric constant of the channel is assumed to be 60. The current-voltage relationship obtained with symmetrical solutions is linear when the applied potential is less than approximately 100 mV but deviates from Ohm's law at a higher applied potential. The reversal potentials obtained with asymmetrical solutions are in agreement with those predicted by the Nernst equation. The conductance exhibits the saturation property observed experimentally. We discuss the implications of these findings for the transport of ions across the potassium channels and membrane channels in general.

Diffusion↗
PubMed1999

A new analytical method of studying post-synaptic currents.

A powerful methodology for analyzing post-synaptic currents recorded from central neurons is presented. An unknown quantity of transmitter molecules released from presynaptic terminals by electrical stimulation of nerve fibers generates a post-synaptic response at the synaptic site. The current induced at the synaptic junction is assumed to rise rapidly and decay slowly with its peak amplitude being proportional to the number of released transmitter molecules. The signal so generated is then distorted by the cable properties of the dendrite, modeled as a time-invariant, linear filter with unknown parameters. The response recorded from the cell body of the neuron following the electrical stimulation is contaminated by zero-mean, white, Gaussian noise. The parameters of the signal are then evaluated from the observation sequence using a quasi-profile likelihood estimation procedure. These parameter values are then employed to deconvolve each measured post-synaptic response to produce an optimal estimate of the transmembrane current flux. From these estimates we derive the amplitude of the synaptic current and the relative amount of transmitter molecules that elicited each response. The underlying amplitude fluctuations in the entire data sequence are investigated using a non-parametric technique based on kernel smoothing procedures. The effectiveness of the new methodology is illustrated in various simulation examples.

Computer Simulation↗
PubMed1999

Water-soluble chitin as a wound healing accelerator.

Water-soluble chitin (WSC) was prepared by controlling degree of deacetylation (DD) and molecular weight of chitin through alkaline and ultrasonic treatment. Its accelerating effect on wound healing in rats was compared with those of chitin and chitosan. Full-thickness skin incision was made on the backs of the rats and then three kinds of powders (chitin, chitosan, WSC) and an aqueous solution of WSC were embedded in the wounds. The tensile strength and the hydroxyproline content of the wounded skins were measured and histological examination was performed. The WSC was found to be more efficient than chitin or chitosan as a wound-healing accelerator. The wound treated with WSC solution was completely reepithelialized, granulation tissues in the wound were nearly replaced by fibrosis and hair follicles were almost healed at 7 days after initial wounding. Also, the WSC-solution-treated skin had the highest tensile strength and the arrangement of collagen fibers in the skin was similar to normal skins. The WSC solution is considered to be a suitable wound-healing agent due to its easy application and high effectiveness.

Acetylation↗
PubMed1999

Clinical characteristics of acute viral lower respiratory tract infections in hospitalized children in Seoul, 1996-1998.

This study was performed to investigate the etiologic agents, age distribution, clinical manifestations and seasonal occurrence of acute viral lower respiratory tract infections in children. We confirmed viral etiologies using nasopharyngeal aspirates in 237 patients of the ages of 15 years or younger who were hospitalized for acute lower respiratory tract infection (ALRI) from March 1996 to February 1998 at Samsung Seoul Hospital, Seoul, Korea. The overall isolation rate was 22.1%. The viral pathogens identified were adenovirus (12.7%), influenza virus type A (21.1%), -type B (13.9%), parainfluenza virus type 1 (13.5%), -type 2 (1.3%), -type 3 (16.0%) and respiratory syncytial virus (21.5%). The occurrence of ALRIs was highest in the first year of life, although parainfluenza virus type 1 infection occurred predominantly in the second year of life and influenza virus caused illnesses in all age groups. The specific viruses are frequently associated with specific clinical syndromes of ALRI. The respiratory agents and associated syndromes frequently have characteristic seasonal patterns. This study will help us to estimate the etiologic agents of ALRI, and establish a program for the prevention and treatment. An annual nationwide survey is necessary to understand the viral epidemiology associated with respiratory illnesses in Korea.

Acute Disease↗
PubMed1999

Various patterns of perfusion-weighted MR imaging and MR angiographic findings in hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: Various clinical subtypes of patients presenting with sudden-onset ischemic stroke have been recognized, but classification of those types is not simple. We identified various patterns of perfusion-weighted MR imaging and MR angiographic findings in hyperacute ischemic stroke with relation to clinical outcomes. METHODS: Twelve patients with symptoms of acute ischemic stroke due to middle cerebral artery occlusion underwent perfusion-weighted MR imaging and MR angiography within 6 hours after the onset of symptoms. Perfusion-weighted imaging was performed with a conventional dynamic contrast-enhanced T2*-weighted sequence, and cerebral blood volume (CBV) maps were then created. CBV maps and MR angiographic findings were compared with 99mTc-HMPAO brain SPECT scans, short-term outcomes, and follow-up imaging findings. RESULTS: The combined CBV and MR angiographic findings were classified into three patterns: arterial occlusion and decreased CBV (n = 8), arterial occlusion and increased CBV (n = 2), and no arterial occlusion and normal CBV (n = 2). These three patterns were strongly related to SPECT findings, short-term outcomes, and follow-up imaging findings. Perfusion on SPECT decreased markedly in the affected regions in all patients with the first pattern, decreased slightly in the second pattern, and was normal in the third pattern. Symptoms were not significantly changed at 24 hours after onset in any of the patients with the first pattern, but resolved completely in all patients with the latter two patterns. Follow-up imaging showed large infarctions in all patients with the first pattern. Initially, no infarction was seen in the second pattern, but watershed infarction developed later in one of these patients. CONCLUSION: Hyperacute ischemic stroke may be differentiated into three imaging patterns with different clinical outcomes. The combined use of perfusion-weighted MR imaging and MR angiography may play a substantial role in guiding the choice of treatment of this disease.

Acute Disease↗
PubMed1999

Nutritional status of Korean peritoneal dialysis patients.

OBJECTIVES: To assess the nutritional status of Korean peritoneal dialysis (PD) patients and to compare with data from Western literature, and to elucidate independent factors determining nutritional status and death. DESIGN: Cross-sectional single-center study. SETTING: Kidney Center, Soon Chun Hyang University Hospital. MATERIALS: Ninety-eight CAPD patients were included. Of these, 54 patients were male, 32 patients were diabetic, mean age was 47.9+/-13.1 years, and mean duration of CAPD was 22.3+/-21.6 months. The patients were followed until death, transfer to hemodialysis (HD) or other units, transplantation, or until 3 years had elapsed after the first evaluation. METHODS: Nutritional status was assessed by subjective global assessment (SGA), biochemical and anthropometric measurements, fat-free edema-free (FFEF) body mass by creatinine (Cr) kinetics, protein equivalent of total nitrogen appearance (PNA), and urea kinetic studies. RESULTS: By SGA score, 53.1% of patients were classified as normal, 44.9% with mild-to-moderate malnutrition, and 2% with severe malnutrition. Patients with malnutrition were significantly older and had higher peritonitis rates, lower serum albumin (Alb), blood urea nitrogen (BUN), serum Cr, FFEF body mass, mid arm muscle circumference, and PNA (p < 0.05). On stepwise multiple regression analysis, the SGA score was negatively correlated with age and peritonitis rate (p < 0.01). At the end of the 3-year follow-up period, 11 patients were still on CAPD, 26 had died, 51 had transferred to HD and 5 to other units, 3 patients had been transplanted, and 2 patients were lost to follow-up. Patients who died during follow-up were older and had higher peritonitis rates and lower total serum protein, Alb, Cr, and FFEF body mass when compared to those who survived (p < 0.05). Independent predictors of death were age, peritonitis rate, and serum Alb (p < 0.01). CONCLUSION: Malnutrition was as common in Korean PD patients as reported in the Western literature. Our data suggests that, to prevent malnutrition and early death, it is important to reduce the peritonitis rate, to improve protein intake, and to prescribe an adequate dose of peritoneal dialysis.

Anthropometry↗